Update Journal Cardiology by GreenX Publishing

VOL 7 ● ISSUE 4 ● 2021 EXCLUSIVE IRISH CARDIOLOGY MEETINGS COVERAGE + CARDIAC AMYLOIDOSIS: CARDIOLOGY Overview, diagnosis, and management hypertension, heart failure, atrial fibrillation and coronary artery disease CARDIOVASCULAR DISEASE IN WOMEN SPECIAL FOCUS ON EXPERT CLINICAL ARTICLES ON

Cardiac care in turbulent times

A message from Priscilla Lynch, Editor

Welcome to the latest edition of Update Cardiology

Over a year into the pandemic so much has changed utterly in healthcare provision.

Despite the very welcome arrival of Covid-19 vaccines, we still don’t know how long this crisis will impact on clinical practice, but it is clear the ramifications will be long lasting across cardiac and stroke services, with waiting lists continuing to climb each month.

While healthcare professionals strive to ensure urgent care is being delivered across the country, and telemedicine has helped many routine appointments continue, the fact remains that many patients are not receiving the necessary early and preventative care they normally would.

Last year, many people experiencing symptoms of acute cardiac incidents and stroke delayed presenting at hospital due to concerns about the coronavirus and not wanting to burden the healthcare system, which meant poorer outcomes for those affected.

The Irish Heart Foundation and individual clinicians took to the airwaves and print media to reassure patients and warn of the consequences of delaying care, and the message sunk in that anyone experiencing symptoms of a stroke or heart attack should follow the normal protocol and call an ambulance without delay.

For those who contract Covid-19 however, it has become clear that there is increased risk of death or ICU admission

in coronary artery disease (CAD) patients, and a significant proportion of hospitalised Covid-19 patients show evidence of acute myocardial injury (10-to-30 per cent) leading to worse prognosis. Observational data also suggests a relatively high rate of abnormal myocardial signal on CMR in patients who recover from acute Covid-19 though the clinical significance is still unclear. To understand and address these particular issues, Prof Robert Byrne, Chair of Cardiovascular Research at the RCSI, is leading the Study of Heart Disease and Immunity After COVID-19 in Ireland (SETANTA), a multicentre, prospective, community-based, cross-sectional study of cardiac complications and haematological abnormalities in patients recovered postCovid-19. The study, which is currently recruiting patients, is scheduled to conduct 12 months follow-up and be completed in June 2022, with the results eagerly awaited.

The need for expert knowledge and CME continues despite Covid-19, and in this issue we feature expert clinical articles on the latest treatment approaches across a broad range of disease areas, including heart failure, hypertension, atrial fibrillation, and addressing the burden of CAD, as well as a very informative look at the management of in-stent restenosis, and a detailed CPD module on the pathophysiology, diagnosis and management of cardiac amyloidosis.

There is also a special focus on cardiovascular disease in women in this edition of Update Cardiology, with a round-up of the latest European Society of Cardiology research showing delayed

diagnosis and treatment of cardiac issues in women, an interview with leading Irish Consultant Interventional Cardiologist Dr Róisín Colleran on raising awareness of female-specific CVD risk factors and presentation differences, and a detailed clinical article on spontaneous coronary artery dissection (SCAD), an important cause of myocardial infarction that occurs much more commonly in women with few or no conventional risk factors.

There is also a very interesting piece on a Sláintecare-funded Community Cardiac Diagnostics Programme in Galway, which is facilitating direct access for local GPs to echocardiography through a mobile service at a number of satellite locations.

While a number of important local and international stroke and cardiology meetings have been cancelled due to Covid-19, this issue carries extensive coverage of the most recent Irish Cardiac Society Annual Scientific Meeting, and a meeting report on the latest Mater Private Cardiology Masterclass for GPs.

So all in all, this is a packed issue that should hopefully prove interesting and useful to all our readers.

Thank you to our expert contributors for taking the time to share their knowledge and advice for the betterment of patient care.

We always welcome new contributors and ideas and suggestions for future content as well as any feedback on our content to-date. Please contact me at priscilla@mindo.ie if you wish to comment or contribute an article. ■

1 Cardiology | Volume 7 | Issue 4 | 2021

Hypertension – some

40 Cardiac amyloidosis: Overview, diagnosis, and management

47 Management of in-stent restenosis

50 Spontaneous coronary artery dissection (SCAD)

54 Sláintecare Galway University Hospital Community Cardiac Diagnostics Service

Editor Priscilla Lynch priscilla@mindo.ie

Sub-editor Emer Keogh emer@greenx.ie

Creative Director Laura Kenny laura@greenx.ie

Advertisements Graham Cooke graham@greenx.ie

Administration Daiva Maciunaite daiva@greenx.ie

Update is published by GreenCross Publishing Ltd, Top Floor, 111 Rathmines Road Lower, Dublin 6 Tel +353 (0)1 441 0024 greencrosspublishing.ie

The contents of Update are protected by copyright. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means – electronic, mechanical or photocopy recording or otherwise – whole or in part, in any form whatsoever for advertising or promotional purposes without the prior written permission of the editor or publisher.

Disclaimer

The views expressed in Update are not necessarily those of the publishers, editor or editorial advisory board. While the publishers, editor and editorial advisory board have taken every care with regard to accuracy of editorial and advertisement contributions, they cannot be held responsible for any errors or omissions contained.

GreenCross Publishing is owned by Graham Cooke graham@greenx.ie

Contents 04 Irish Cardiac Society 71st Annual Scientific Meeting 12 Mater Private Cardiology Masterclass for GPs 15 Atrial fibrillation: An overview 22 Addressing the burden of coronary heart disease 26 ESC: Cardiovascular disease in women 27 Interview on raising awareness of cardiovascular disease in women 28 Positively impacting the burden of heart failure through partnership

practical pointers

COMBINING POWER AND CONFIDENCE

AGAINST LDL-C* IN THE TREATMENT OF HYPERCHOLESTEROLAEMIA

Suvezen is indicated for substitution therapy in adult patients who are adequately controlled with rosuvastatin and ezetimibe given concurrently at the same dose level as in the fixed combination, but as separate products, as adjunct to diet for treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or homozygous familial hypercholesterolaemia1

Prescribing Information: Suvezen (rosuvastatin/ ezetimibe) film-coated tablets Please refer to the Summary of Product Characteristics (SmPC) for full prescribing details. Presentations: Suvezen 10mg/10mg, 20mg/10mg and 40mg/10mg: Each film-coated tablet contains 10mg; 20mg or 40mg of rosuvastatin (as rosuvastatin calcium) respectively, and 10mg ezetimibe. Indication: Suvezen is indicated for substitution therapy in adult patients who are adequately controlled with rosuvastatin and ezetimibe given concurrently at the same dose level as in the fixed combination, but as separate products, as adjunct to diet for treatment of primary hypercholesterolaemia (heterozygous familial and non-familial) or homozygous familial hypercholesterolaemia. Dosage and Administration: The patient should be on and continue, an appropriate lipid-lowering diet, during treatment with Suvezen. Suvezen is not suitable for initial therapy. Treatment initiation or dose adjustment, if necessary, should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible. Patient should use the strength corresponding to their previous treatment. The recommended dose is one Suvezen tablet daily. To be administered at any time of the day, with or without food. The tablet should be swallowed whole with a drink of water. If co-administered with bile acid sequestrant (BAS), administration of Suvezen should occur either ≥2 hours before or ≥4 hours after administration of a BAS. Special populations: Paediatric (<18 years): Safety and efficacy has not been established. Elderly (>70 years): Starting dose of 5 mg rosuvastatin is recommended. The combination is not suitable for initial therapy. Hepatic impairment: Mild: No dosage adjustment is required. Moderate/Severe: Treatment with Suvezen is not recommended. Renal impairment: Mild: No dose adjustment is necessary. Moderate (creatinine clearance <60 ml/min): The recommended start dose is rosuvastatin 5mg. Race: The recommended start dose is rosuvastatin 5 mg for patients of Asian ancestry due to increased systemic exposure. The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose. Suvezen 40 mg/10 mg tablets are contraindicated in these patients. Genetic polymorphisms: In patients who are known to have specific types of genetic polymorphisms that can lead to increased rosuvastatin exposure, a lower daily dose of Suvezen is recommended. Dosage in patients with pre-disposing factors to myopathy: The recommended start dose is rosuvastatin 5mg in patients with pre-disposing factors to myopathy. Suvezen 40 mg/10 mg tablets are contraindicated in some of these patients. Concomitant therapy: The risk of myopathy (including rhabdomyolysis) is increased when Suvezen is administered concomitantly with certain medicinal products that may increase the plasma concentration of rosuvastatin (e.g. ciclosporin and certain protease inhibitors including combinations of ritonavir with atazanavir, lopinavir, and/or tipranavir). Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Suvezen therapy. In situations where co-administration of these medicinal products with Suvezen is unavoidable, the benefit and the risk of concurrent treatment and rosuvastatin dosing adjustments should be carefully considered. Contraindications: Hypersensitivity to the active substances or excipients. Pregnancy, breast-feeding and in women of childbearing potential not using appropriate contraceptive measures. Active liver disease or any serum transaminase elevations which are unexplained, persistent or exceeding 3x the upper limit of normal (ULN).

Severe renal impairment (creatinine clearance <30ml/min); myopathy or receiving concomitant ciclosporin. 40mg/10mg dose contraindicated in patients with pre-disposing factors for myopathy/rhabdomyolysis; such factors include: Moderate renal impairment (creatinine clearance <60ml/min), hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG-CoA reductase inhibitor or fibrate, alcohol abuse, situations where an increase in plasma levels of rosuvastatin may occur, Asian patients, concomitant use of fibrates. Precautions and Warnings: Skeletal muscle effects: have been reported in rosuvastatintreated patients with all doses and in particular with doses >20mg. As with other HMG-CoA reductase inhibitors, reporting rate for rhabdomyolysis is associated with use at doses >40mg. Post-marketing experience with ezetimibe, cases of myopathy and rhabdomyolysis have been reported. If myopathy is suspected based on muscle symptoms or is confirmed by a creatine phosphokinase (CPK) level, Suvezen and any of these other agents that the patient is taking concomitantly should be immediately discontinued. All patients starting therapy with Suvezen should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness, particularly if associated with malaise or fever. Creatine kinase (CK) measurement: CK should not be measured following strenuous exercise or in the presence of a plausible alternative cause of CK increase. If CK levels are significantly elevated at baseline (>5x ULN) a confirmatory test should be carried out within 5 – 7 days. If the repeat test confirms a baseline CK >5x ULN, treatment should not be started. Patients with pre-disposing factors for myopathy/rhabdomyolysis: Caution should be exercised in these patients. Risk: benefit of treatment should be considered and clinical monitoring is recommended. CK levels should be measured in these patients. Therapy should be discontinued if CK levels are markedly elevated (>5x ULN) or if muscular symptoms are severe and cause daily discomfort. If symptoms resolve and CK levels return to normal, then consideration should be given to re-introducing treatment at the lowest dose. Immune-mediated necrotising myopathy (IMNM): Clinically characterised by proximal muscle weakness and elevated serum CK, has been reported very rarely during or after treatment with statins, including rosuvastatin, despite discontinuation of statin treatment. In clinical trials an increase in the incidence of myositis and myopathy has been seen in patients receiving other HMG-CoA reductase inhibitors together with fibric acid derivatives. Suvezen should not be used in any patient with an acute, serious condition suggestive of myopathy or predisposing to the development of renal failure secondary to rhabdomyolysis (e.g. sepsis, hypotension, major surgery, trauma, severe metabolic, endocrine and electrolyte disorders; or uncontrolled seizures). Liver effects: In controlled co-administration trials in patients receiving ezetimibe with statin, consecutive transaminase elevations ≥3x ULN have been observed. It is recommended that liver function tests be carried out prior to, and 3 months following, the initiation of treatment. Rosuvastatin should be discontinued or the dose reduced if the level of serum transaminases is >3x ULN. The reporting rate for serious events is higher at the 40mg dose. In patients with secondary hypercholesterolaemia caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated prior to initiating therapy with rosuvastatin. Liver disease and alcohol: As with other HMG-CoA reductase inhibitors, rosuvastatin should be used with

Reference: 1. Suvezen Summary of Product Characteristics

caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease. Renal effects: Proteinuria has been observed in patients treated with higher doses of rosuvastatin and was transient or intermittent in most cases. Proteinuria has not been shown to be predictive of acute or progressive renal disease. An assessment of renal function should be considered during routine follow-up of patients treated with a dose of 40mg. Diabetes mellitus: Some evidence suggests that statins raise blood glucose and in some patients, at high risk of future diabetes, may produce a level of hyperglycaemia where formal diabetes care is appropriate. This risk, however, is outweighed by the reduction in vascular risk with statins and therefore should not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 – 6.9mmol/l, BMI >30kg/m2, raised triglycerides, hypertension) should be monitored both clinically and biochemically according to national guidelines. Interstitial lung disease: Exceptional cases have been reported with some statins, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected, statin therapy should be discontinued. Protease inhibitors: Increased systemic exposure to rosuvastatin has been observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. Consideration should be given both to the benefit of lipid lowering by use of Suvezen in HIV patients receiving protease inhibitors and the potential for increased rosuvastatin plasma concentrations when initiating and up titrating rosuvastatin doses in patients treated with protease inhibitors. The concomitant use with certain protease inhibitors is not recommended unless the dose of rosuvastatin is adjusted. Fibrates: The safety and efficacy of ezetimibe administered with fibrates have not been established. If cholelithiasis is suspected in a patient receiving Suvezen and fenofibrate, gallbladder investigations are indicated and therapy should be discontinued. Anticoagulants: If Suvezen is added to warfarin, another coumarin anticoagulant, or fluindione, the International Normalised Ratio (INR) should be appropriately monitored. Fusidic acid: Suvezen must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. In patients where the use of systemic fusidic acid is considered essential, statin treatment should be discontinued throughout the duration of fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination. The patient should be advised to seek medical advice immediately if they experience any symptoms of muscle weakness, pain or tenderness. Statin therapy may be re-introduced seven days after the last dose of fusidic acid. In exceptional circumstances, where prolonged systemic fusidic acid is needed, e.g., for the treatment of severe infections, the need for co-administration of Suvezen and fusidic acid should only be considered on a case by case basis and under close medical supervision. Suvezen contains lactose monohydrate and sodium: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’. Interactions: Contraindicated combinations: Ciclosporin. Not-recommended combinations: Fibrates and other lipidlowering products, protease inhibitors, transporter protein inhibitors and fusidic acid. Other possible interactions: Cytochrome P450 enzymes, antacids, colestyramine, anticoagulants, Vitamin K antagonists, erythromycin, oral contraceptive/hormone replacement therapy. When co-administering rosuvastatin with other medicinal products known to increase exposure to rosuvastatin, doses should be adjusted (see SmPC for full details). The maximum daily dose should be adjusted so that the expected rosuvastatin exposure would not likely exceed that of a 40mg daily dose of rosuvastatin taken without interacting medicinal products. Fertility, Pregnancy and Breastfeeding: No clinical data are available on the use of ezetimibe during pregnancy. Potential risk from inhibition of HMG-CoA reductase outweighs the advantage of treatment during pregnancy. If a patient becomes pregnant during use of Suvezen, treatment should be discontinued immediately. Animal studies have shown excretion of medicinal product through breast milk. However, there are no data in humans. No clinical trial data on the effects of fertility in humans. Adverse Reactions: Adverse drug reactions previously reported with one of the individual components (ezetimibe or rosuvastatin) may be potential undesirable effects with Suvezen. Common (≥1/100 to <1/10): diabetes mellitus, headache, dizziness, constipation, nausea, abdominal pain, diarrhoea, flatulence, myalgia, ALT and/or AST increased, asthenia and fatigue. Uncommon (≥1/1,000 to <1/100): decreased appetite, paraesthesia, hot flush, hypertension, cough, dyspepsia, gastroesophageal reflux disease, nausea, dry mouth, gastritis, pruritus, rash, urticaria, arthralgia, muscle spasms, neck pain, back pain, muscular weakness, pain in extremity, ALT and/or AST increased, blood CPK increased, gamma-glutamyltransferase increased, liver function test abnormal, chest pain, pain, asthenia, oedema peripheral. Rare (≥1/10,000 to <1/1,000): thrombocytopenia, hypersensitivity reactions including angioedema, pancreatitis, increased hepatic transaminases, myopathy (including myositis), rhabdomyolysis, lupus-like syndrome and muscle rupture. Very rare (<1/10,000): polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, haematuria, gynaecomastia. Not known: thrombocytopenia, hypersensitivity (including rash, urticaria, anaphylaxis and angioedema), depression, peripheral neuropathy, sleep disturbances (including insomnia and nightmares), dizziness, paraesthesia, cough, dyspnoea, diarrhoea, pancreatitis, constipation, hepatitis, cholelithiasis, cholecystitis, Stevens Johnson syndrome, erythema multiforme, immune-mediated necrotising myopathy, tendon disorders (sometimes complicated by rupture), myalgia, myopathy/rhabdomyolysis, oedema, asthenia. See SmPC for full details on adverse reactions. Legal Category: POM. Marketing Authorisation Numbers: 10mg/10mg: PA0540/193/001; 20mg/10mg: PA0540/193/002; 40mg/10mg: PA0540/193/003. Marketing Authorisation Holder: Sanofi-Aventis Ireland Ltd. T/A SANOFI, Citywest Business Campus, Dublin 24, Ireland. Further information is available from: Sanofi, 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi.com Date of Preparation: December 2020.

Adverse events should be reported.

Reporting forms and information can be found at www.hpra.ie; email: medsafety@hpra.ie Adverse events should also be reported to Sanofi Ireland Ltd. Tel: 01 403 5600. Alternatively, send via email to IEPharmacovigilance@sanofi.com

* LDL-C: Low-density lipoprotein Cholesterol ** Suvezen is available in 3 doses in Ireland. Suvezen 10mg/10mg, 20mg/10mg and 40mg/10mg: Each film-coated tablet contains 10mg; 20mg or 40mg of rosuvastatin (as rosuvastatin calcium) respectively, and 10mg ezetimibe.

20 mg /10 mg Rosuvastatin

10 mg /10 mg Rosuvastatin

40 mg /10 mg

+ Ezetimibe

Rosuvastatin + Ezetimibe

Single-pill combination of rosuvastatin and ezetimibe available in 3 doses*

MAT-IE-2100425 (v1.0) – March 2021

Irish Cardiac Society 71st Annual Scientific Meeting: Conference report

AUTHOR: Pat Kelly

ICS embraces virtual conference format

The Irish Cardiac Society (ICS) 71st Annual Scientific Meeting, which took place on 1-3 October 2020, was opened by outgoing ICS President Prof Jim Crowley, who thanked those who attended in its virtual format and expressed his hope that the next meeting could return to its normal face-to-face setting.

“I would like to thank the speakers for contributing,” said Prof Crowley. “We have a very high standard in terms of the quality of presentations and I hope you will find that enjoyable, and hopefully next year we will be back to the live [face-to-face] format, although we don’t know where we will be until we sort out the pandemic. But certainly, this current format lends itself to

certain presentations and I think it is likely that this format will continue to provide us with interesting meetings and methods for educating ourselves in the field of cardiology and other areas of medicine.”

Prof Crowley also acknowledged the

importance of sponsors’ input to the meeting, noting that their symposia “have added to the academic input of this meeting”.

The Thursday and Friday had sessions in association with the Irish Nurses Cardiovascular Association and the Irish Cardiac Clinical Physiologists and heard presentations on a variety of topics ranging from virtual drug titrations and remote selfcare, to echo reporting and Covid-19. Prof Jim O’Neill, Consultant Cardiologist, Mater Misericordiae University Hospital, Dublin, also delivered a presentation to the Friday session entitled ‘Cardiac transplant’, as well as a range of oral abstracts, moderated posters and general posters.

Rise of the machines in cardiology

The first of the Saturday sessions was chaired by Prof Aaron Peace, Consultant Cardiologist and Research and Development Director of the Western Health and Social Care Trust (WHSCT). Prof Peace introduced Prof Nico Bruining, Head, eCardiology, Clinical Epidemiology and Innovation (KEI), Thoraxcentre, Erasmus MC, Rotterdam, The Netherlands, and Editor-in-Chief of the European Heart Journal – Digital Health.

Prof Peace noted that Covid-19 has been “a catalyst to digital cardiology and the provision of virtual care and we are seeing an increase in the use of tools such as the AliveCor device”, which allows patients to take a medical-grade ECG in just 30 seconds.

Prof Bruining addressed the meeting

on the topic ‘Developments in digital cardiology’ and told the attendees: “The European Society of Cardiology (ESC) realised a few years ago that e-health, now mainly called digital health, was rapidly gaining more importance and that more attention needed to be given to it.” He

pointed out that the ECS has developed a ‘roadmap’ for digital activities that it wants to undertake, which was outlined in a position statement from the Society.

Artificial intelligence

“A good illustration of the growing interest in artificial intelligence (AI) is the rapidly-increasing number of publications about the use of machine learning in the titles,” said Prof Bruining. “AI is a focus of attention at the moment…. AI can be extremely helpful in processing the ever-growing amount of data that we collect on patients. The most optimal information would be if the software could serve us for clinical decision support, something that has been at the top of our wish-list for many years, but

Volume 7 | Issue 4 | 2021 | Cardiology 4

Prof Nico Bruining

may now be realised.”

Prof Bruining explained that in his own centre, he and his colleagues are examining how they can practically implement these new technologies. “That starts with first collecting all the clinical data that we generate from an admitted patient…. AI software is also used in subcomponents in the care process, such as image and signal analysis.”

A number of practical AI solutions have already been implemented, he explained, particularly in the area of cardiovascular imaging analysis, including calcium

detection in CT images, among other applications. “Echocardiography is the workhorse in the cardiovascular system and it must all be processed,” said Prof Bruining. “That can become a huge amount of work in busy centres and AI can also be deployed here to help out.”

In this regard, Prof Bruining pointed to a study by Attia et al, which described the process to construct a fully-automated pipeline for the assessment of cardiac structure, function and disease detection. The authors describe this pipeline as “fully scalable, as evidenced by our analysis of >14,000 echocardiograms for this article on

a 14-node compute cluster, all in a period of <three weeks”.

Computer models

Another emerging form of image analysis is to confer the images to a patientspecific computer model, he said, and use it for further calculations. Prof Bruining presented the conference with an example of a practical application of this in a patient undergoing reconstruction of a microvalve, as well as case studies of other patients to help determine patientspecific potential paravalvular leakage in transcatheter aortic valve replacement prosthesis prior to implantation.

The ‘Jekyll and Hyde’ of atherosclerosis

In a session chaired by Dr Ian Menown, Consultant Cardiologist and Director of Invasive Cardiology at the Craigavon Cardiac Centre, Co Armagh, attendees at the conference heard a presentation from Prof Alberto Zambon, Director at the Lipoprotein Core Laboratory, Centre for Atherosclerosis Prevention and Treatment, Department of Medicine, University of Padua, Italy. Prof Zambon spoke on the topic of ‘Triglycerides in atherosclerosis: A strange case of Dr Jekyll and Mr Hyde’.

“It’s a strange story, because if we look at lipoproteins, we have a clear idea of the lipoproteins that are dangerous for our arteries,” said Prof Zambon. “But then we have a range of proteins where we are not exactly sure what they do – are they bad or good, do they do anything or do something?” In his presentation, Prof Zambon focused on the mild-to-moderate range of triglycerides in the range of two-to-10mmol/L not associated with increased risk of pancreatitis, but with an increased risk of cardiovascular disease.

“Triglycerides might not be dangerous, but the cholesterol in the triglyceride-rich lipoproteins is what drives the results in these studies and that is the reason why

once you adjust for the cholesterol inside the lipoprotein, the risk [of coronary heart disease] is flattened.”

Prof Zambon presented a range of studies on the topic to illustrate his point and explained that the cause of ischaemic heart disease is not triglycerides by themselves, but “it is the cholesterol inside the triglyceride-rich lipoproteins that counts. That is why when you adjust for it, the effect of triglycerides is gone.”

‘Pears and apples’ He provided an overview of the results of studies on the genetics and pathophysiology of coronary heart disease, telling the conference: “Comparing triglyceride-rich lipoproteins

Prof Alberto Zambon

and LDL is like comparing pears and apples, but they share one common feature – each of these lipoproteins contains one molecule of LDL.”

Prof Zambon told the attendees: “I believe there is plenty of evidence and robust data to suggest that triglycerides are the ‘Mr Hyde’ of lipoproteins, not the ‘Dr Jekyll’. Raised triglyceride concentration is likely a marker of cholesterol – remember, we are always talking about how cholesterol carried in triglyceride-rich lipoproteins is indeed a causal risk factor for cardiovascular disease and keep in mind, one triglyceride-rich lipoprotein is as

5 Cardiology | Volume 7 | Issue 4 | 2021

Triglycerides might not be dangerous, but the cholesterol in the triglyceride-rich lipoproteins is what drives the results in these studies...

atherogenic for your arteries as one LDL.”

Prof Zambon concluded: “Available evidence suggests that the inflammatory components of the plaque in atherosclerosis are indeed modulated by the triglyceride-

rich lipoproteins. I have shown that plaque regression seems to be greater when both LDL-C and TG plasma levels are controlled or at their goals and at near-optimal LDL-C levels, short- to medium-term risk of cardiovascular events remains high

when triglycerides are high, particularly higher than two or 2.5mmol. There are studies showing that approaching, on top of LDL-C, using triglyceride-lowering agents effectively reduces cardiovascular risk in patients with elevated triglycerides.”

The evolution of catheter ablation

The next presenter in the Saturday morning session was Dr Ed Cronin, Associate Professor at the Lewis Katz School of Medicine at Temple University, Philadelphia, US, who addressed the meeting on the topic ‘Catheter ablation of ventricular arrhythmias’. Dr Cronin provided an overview of the history of the development of ablation in ventricular tachycardia since the first procedure in 1982, as well as case studies and highlycited papers, which he has authored, including the global consensus document 2019 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Catheter Ablation of Ventricular Arrhythmias

Dr Cronin also outlined the process of drafting a recommendation and stressed how “this process is very detailed, because every single word has to mean exactly what you want it to mean” and involves meetings, redrafting, consensus, and eventually a voting process. “It’s easy to criticise clinical documents, but it’s a lot harder to write them,” he told the meeting.

Future advances

Dr Cronin touched on potential future advances in the medium-term for VT ablation. “There are two things that deserve particular mention,” he told the conference. “The first is electroporation, or pulse field ablation, which has been very exciting for atrial fibrillation. It’s a little ironic because it harkens back to DC current ablation; it is essentially the same energy, but delivered in a very different way and in a very controlled way compared to the first VT ablation 38 years ago. These catheters… were actually

designed for atrial fibrillation ablation and I think it’s something we are going to be using for atrial fibrillation before too long, and routinely for pulmonary vein isolation. It’s really nicely positioned for that application because the left atrial myocardium is very thin and there are structures around it like the oesophagus that are very important and that you want to protect. Pulse field ablation can be very tissue-specific, so you can injure only cardiac tissue and not oesophageal tissue.

“For VT ablation, first of all for focal VTs, the existing radiofrequency catheters are very good, so they would have to design a new catheter,” Dr Cronin continued.

“It might be useful for areas like the LV summit that might be anatomically challenging, where there are coronary arteries in the way, etc. The other area it might be used for is large-scale substrate ablation in the LV, which would probably be very useful, because ablation lesions

in the LV, especially in scar, are actually not terribly effective at the moment. At best, they are about 5mm deep and we have not seen a reduction in LV function with catheter ablation in VT… part of the reason is probably that abrasion lesions are not that big or deep anyway, so we would find it hard to cause a reduction in LV function.”

Imaging

Dr Cronin explained that his concern in pulsed-field ablation in that setting is that it is possible to create very large lesions with this technology, “and that’s something we have to be very careful of”. He also spoke about non-invasive radio ablation for VT.

“The idea is that you image the patient, perhaps do an EP [electrophysiology] study for induction or perhaps even mapping of VT, often in the context of a prior ablation that has been unsuccessful, and you fuse these different imaging modalities,” which would include a CT scan, to build an anatomical model of the heart to highlight areas to be treated, said Dr Cronin. These areas are then treated with radiation therapy via a standard radiation scanner.

“This is obviously a very novel use [of this technology], and I would say it seems to be very complex to do and there are a lot of steps to it. There are also questions over radiation and toxicity and whether this could cause problems such as coronary stenosis, lung damage or other tissue damage over time. But there are some very exciting results and there is a lot to learn,” Dr Cronin concluded.

Volume 7 | Issue 4 | 2021 | Cardiology 6

Dr Ed Cronin

Rosuvastatin

/ Ezetimibe

Lipocomb

GET LOWER

ESC TREATMENT TARGETS1

Get your patient’s LDL-C down even lower to <1.8mmol/L1

Lipocomb® (rosuvastatin/ezetimibe) Abbreviated Prescribing

Information: Please refer to the Summary of Product Characteristics before prescribing.

COMPOSITION*: Lipocomb 10 mg/10 mg, 20 mg/10 mg hard capsules contain 10 mg rosuvastatin zinc (ros)/10 mg ezetimibe (eze), 20 mg ros/10 mg eze. INDICATIONS*:

Treatment of hypercholesterolemia as an adjunct to diet as substitution therapy in adult patients adequately controlled with the individual substances given concurrently at the same dose level as in the fixed dose combination, but as separate products. DOSAGE AND ADMINISTRATION*: One capsule once daily of the given strength with or without food.

Lipocomb is not suitable for initial therapy. Treatment initiation or dose adjustment if necessary should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible. Appropriate lipid-lowering diet should continue during treatment. Children and adolescents: not recommended. Elderly patients: A start dose of 5 mg rosuvastatin is recommended in patients > 70 years. The combination is not suitable for initial therapy. Patients with renal insufficiency: No dose adjustment is necessary in patients with mild to moderate renal impairment. The recommended start dose is rosuvastatin 5 mg in patients with moderate renal impairment (creatinine clearance < 60 ml/min). The use of rosuvastatin in patients with severe renal impairment is contraindicated for all doses (see section CONTRAINDICATIONS*).

Lipocomb® (rosuvastatin/ezetimibe) Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION*: Lipocomb 10 mg/10 mg, 20 mg/10 mg hard capsules contain 10 mg rosuvastatin zinc (ros)/10 mg ezetimibe (eze), 20 mg ros/10 mg eze. INDICATIONS*: Treatment of hypercholesterolemia as an adjunct to diet as substitution therapy in adult patients adequately controlled with the individual substances given concurrently at the same dose level as in the fixed dose combination, but as separate products. DOSAGE AND ADMINISTRATION*: One capsule once daily of the given strength with or without food. Lipocomb is not suitable for initial therapy. Treatment initiation or dose adjustment if necessary should only be done with the monocomponents and after setting the appropriate doses the switch to the fixed dose combination of the appropriate strength is possible. Appropriate lipid-lowering diet should continue during treatment. Children and adolescents: not recommended. Elderly patients: A start dose of 5 mg rosuvastatin is recommended in patients > 70 years. The combination is not suitable for initial therapy. Patients with renal insufficiency: No dose adjustment is necessary in patients with mild to moderate renal impairment. The recommended start dose is rosuvastatin 5 mg in patients with moderate renal impairment (creatinine clearance < 60 ml/min). The use of rosuvastatin in patients with severe renal impairment is contraindicated for all doses (see section CONTRAINDICATIONS*).

Hepatic impairment: No dosage adjustment is required in patients with mild hepatic insufficiency (Child Pugh score 5 to 6). Treatment with Lipocomb is not recommended in patients with moderate (Child Pugh score 7 to 9) or severe (Child Pugh score >9) liver dysfunction. Lipocomb is contraindicated in patients with active liver disease (see section CONTRAINDICATIONS*). Patients of Asian ancestry or pre-disposing factors to myopathy: recommended starting dose is rosuvastatin 5 mg. The fixed dose combination is not suitable for initial therapy. Monocomponent preparations should be used to start the treatment or to modify the dose. Genetic polymorphisms: for patients that have types of polymorphisms that can lead to increased rosuvastatin exposure, a lower daily dose of Lipocomb is recommended.

Concomitant therapy: risk of myopathy increased when Lipocomb taken with medicinal products that interact with transporter proteins (OATP1B1 and BCRP) and increase rosuvastatin exposure, including ciclosporin, regorafenib, velpatasvir, combination of ritonavir with atazanavir, or combinations of ritonavir with ombitasvir and paritaprevir and dasabuvir, or combination of ritonavir with lopinavir and/or tipranavir, , combination of grazoprevir with elbasvir, combination of glecaprevir with pibrentasvir. Whenever possible, alternative medications should be considered, and, if necessary, consider temporarily discontinuing Lipocomb therapy. In situations where co-administration of these medicinal products with Lipocomb is unavoidable, the benefit and the risk of concurrent treatment and rosuvastatin dosing adjustments should be carefully considered.

CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any of the excipients, active liver disease including unexplained persistent elevations of serum transaminases and any serum transaminase elevation exceeding 3x the upper limit of normal (ULN). During pregnancy and breast-feeding and in women of childbearing potential not using appropriate contraceptive measures (see section PREGNANCY* and BREASTFEEDING*), severe renal impairment (creatinine clearance < 30 ml/min), myopathy, concomitant ciclosporin (see section INTERACTIONS*). WARNINGS*: Skeletal Muscle Effects: effects on skeletal muscle e.g. myalgia, myopathy, and, rarely, rhabdomyolysis have been reported in rosuvastatin-treated patients with all doses and in particular with doses > 20 mg. Stop treatment if myopathy is suspected based on muscle symptoms or is confirmed by a creatine kinase level. Liver effects: liver function tests should be carried out 3 months following the initiation of rosuvastatin treatment. Stop rosuvastatin or reduce dose if serum transaminase level is greater than 3 times the upper limit of normal. In secondary hypercholesterolaemia

CV risk LDL-C target

High** <1.8mmol/L

Very High* <1.4mmol/L

caused by hypothyroidism or nephrotic syndrome, the underlying disease should be treated before starting Lipocomb. Not recommended in patients with moderate or severe hepatic insufficiency. Renal effects: Proteinuria observed with higher doses of rosuvastatin, in particular 40 mg. Creatine Kinase (CK) Measurement: should not be measured following strenuous exercise or plausible alternative cause of CK increase. A confirmatory test should be carried out within 5-7 days if CK levels are significantly elevated at baseline (CK > 5xULN). If repeat tests confirms baseline CK >5xULN, treatment should not be started. Fusidic acid: Lipocomb must not be co-administered with systemic formulations of fusidic acid or within 7 days of stopping fusidic acid treatment. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving fusidic acid and statins in combination. Where the use of systemic fusidic acid is considered essential, statin treatment should be stopped throughout duration of fusidic acid treatment. Statin therapy may be re-introduced seven days after last dose of fusidic acid. In cases of prolonged systemic fusidic acid is needed, the need for coadministration of Lipocomb and fusidic acid should only be considered on a case by case basis and under close medical supervision. Before treatment: Use with caution in patients with pre-disposing factors for myopathy/rhabdomyolysis, including renal impairment, hypothyroidism, personal or family history of hereditary muscular disorders, previous history of muscular toxicity with another HMG CoA reductase inhibitor or fibrate, alcohol abuse, age > 70 years, situations where an increase in plasma levels may occur, or concomitant use of fibrates. Whilst on treatment: CK levels should be measured in patients with inexplicable muscle pain, weakness or cramps, particularly if associated with malaise or fever. Stop treatment if CK levels are markedly elevated (>5xULN) or if muscular symptoms are severe and cause daily discomfort. Routine monitoring of CK levels in asymptomatic patients not warranted. Rare reports of an immune-mediated necrotising myopathy (IMNM) during or after treatment with statins. Combination with gemfibrozil is not recommended. The combined use of Lipocomb with fibrates or niacin should be carefully weighed against the potential risks of such combinations. Race: increased exposure to rosuvastatin in Asian patients. Protease inhibitors: Increased systemic exposure to rosuvastatin observed in subjects receiving rosuvastatin concomitantly with various protease inhibitors in combination with ritonavir. Concomitant use with certain protease inhibitors not recommended unless the dose of Lipocomb is adjusted. Interstitial lung disease: Stop statin therapy if suspected. Diabetes mellitus: Statins as a class raise blood glucose and in some patients, at high risk of future diabetes, may produce level of hyperglycemia where formal diabetes care is appropriate. Risk outweighed by reduction in vascular risk with statins, and should therefore not be a reason for stopping statin treatment. Patients at risk (fasting glucose 5.6 to 6.9 mmol/L, BMI>30kg/m2, raised triglycerides, hypertension) should be monitored according to national guidelines.

Fibrates: safety and efficacy of ezetimibe administered with fibrates have not been established. If cholelithiasis suspected in patient receiving Lipocomb and fenofibrate, gallbladder investigations are indicated and this therapy should be discontinued. Anticoagulants: Monitor international normalised ratio (INR) if Lipocomb is added to warfarin, another coumarin anticoagulant, or fluindione. Paediatric population: Not recommended. Liver disease and alcohol: Use with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease. INTERACTION(S)*: Contraindicated: Ciclosporin. Not recommended: protease inhibitors (see section DOSAGE AND ADMINISTRATION*), transporter protein inhibitors, gemfibrozil and other lipid-lowering products, fusidic acid. Other interactions: antacid, erythromycin, vitamin K antagonists, oral contraceptives/hormone replacement therapy (HRT), colestyramine, statins. Drug interactions resulting from cytochrome P450-mediated metabolism are not expected. PREGNANCY AND BREASTFEEDING*: Lipocomb is contraindicated in pregnancy and breastfeeding. Women of childbearing potential should use appropriate contraceptive measures.

FERTILITY*: DRIVE AND USE MACHINES*: dizziness may occur during treatment (see section UNDESIRABLE EFFECTS*). UNDESIRABLE EFFECTS*: Common: diabetes mellitus, headache, dizziness, constipation, nausea, abdominal pain, diarrhoea, flatulence, myalgia, asthenia, fatigue, ALT and/or AST increased. Uncommon: decreased appetite, paraesthesia, hot flush, hypertension, cough, dyspepsia, gastrooesophageal reflux disease, nausea, dry mouth, gastritis, pruritus, rash, urticaria, arthralgia, muscle spasms, neck pain, back pain, muscular weakness, pain in extremity, chest pain, pain, asthenia; oedema peripheral, ALT and/or AST increased, blood CPK increased, gamma-glutamyltransferase increased, liver function test abnormal. Rare: thrombocytopenia, hypersensitivity reactions including angioedema, pancreatitis, increased hepatic transaminases, myopathy (including myositis), rhabdomyolysis. Very rare: polyneuropathy, memory loss, jaundice, hepatitis, arthralgia, haematuria, gynecomastia. Not known: thrombocytopenia, hypersensitivity (including rash, urticaria, anaphylaxis and angioedema), depression, peripheral neuropathy, sleep disturbances (including insomnia and nightmares), dizziness, paraesthesia, cough, dyspnoea, diarrhoea, pancreatitis, constipation, hepatitis, cholelithiasis, cholecystitis, Stevens-Johnson syndrome, erythema multiforme, immune-mediated necrotising myopathy, tendon disorders, sometimes complicated by rupture, arthralgia, myalgia, myopathy/ rhabdomyolysis, oedema, asthenia. OVERDOSE*: PROPERTIES*: Rosuvastatin is a selective and competitive inhibitor of HMG CoA reductase. Ezetimibe is in a new class of lipid-lowering compounds that selectively inhibit the intestinal absorption of cholesterol and related plant sterols. PRESENTATION*: Pack of 30 capsules of Lipocomb 10 mg/10 mg, and 20 mg/10 mg. Marketing Authorisation Holder: EGIS Pharmaceuticals PLC, Kereszturi ut 30-38, H-1106 Budapest, Hungary. PA1470/004/001-002. Legal

Classification for Supply: POM. Local Representative in Ireland: Servier Laboratories (Ireland) Ltd, Second Floor, 19 Lr. George’s Street, Dun Laoghaire, Co. Dublin A96 ER84, Ireland. Tel (01) 6638110, www.servier.ie

* For complete information, please refer to the complete Summary of Product Characteristics for Lipocomb® at www.hpra.ie

Date of last revision of text: Sep 2020 (Date of last approved SmPC: March 2019) Date of Preparation November 2020, 2021 C1 LCB Press Ad.

1. Mach et al. 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias, European Heart Journal (2019) 00, 1-78’ * Patients with: documented CVD, Diabetes Mellitus with organ damages, Severe CKD (chronic kidney disease), a calculated 10 year risk of fatal CVD ≥ 10%, Familial Hypercholesterolaemia with CVD/risk factor. **Patients with: Markedly elevated single risk factors (in particular cholesterol > 8mmol/L or BP ≥ 180/110 mmHg), Familial Hypercholesterolaemia, Diabetes Mellitus, Moderate CKD (chronic kidney disease), a calculated 10 year risk of fatal CVD ≥ 5% and <10%.

Rosuvastatin / Ezetimibe

Get your patient’s LDL-C down even lower to <1.8mmol/L1

Strong range of research presentations at virtual ICS Annual Scientific Meeting

The always highly-anticipated ICS Brian Maurer Young Investigator Award, supported by Servier, featured a varied range of speakers and topics, ranging from ventricular arrhythmia to PCSK9 inhibition. The 2020 judging panel comprised Prof Jim Crowley, President, ICS; Prof Albert McNeill, Past-President, ICS; and Prof Ken McDonald, PastPresident, ICS.

The finalist presenters and their topics were: Dr Ailis Pollock, St James’s Hospital, Dublin, on ‘Covid-19 and QTc: Is hydroxychloroquine worth the risk? A review of QT prolongation in hospitalised Covid-19 patients treated with hydroxychloroquine and azithromycin’.

Dr Max Waters, Tallaght University Hospital, Dublin, Ireland, then delivered a presentation on ‘A hierarchal analysis of eligibility for PCSK9 inhibition in Ireland: Bridging the divide between the NCPE managed access protocol and ESC/ EAS guidelines’.

Next to present was Dr Angela McInerney, Cardiovascular Institute, Hospital Clínico San Carlos, IdISSC, Madrid, Spain, on ‘Impact of morbid obesity and obesity phenotype on outcomes post-transcatheter aortic valve replacement’.

The final presentation was delivered by Dr Bronagh Kelly, Adult Congenital Heart Disease Department, Royal Victoria

Hospital, Belfast, Northern Ireland, who presented her observations on ‘Predictors of ventricular arrhythmia identified from follow-up of tetralogy of fallot’.

During his closing comments at the conference, Prof Crowley announced that the winner of the 2020 award was Dr Angela McInerney.

The Intervention Case Competition, held on the Friday evening of the conference and supported by AstraZeneca, also saw an extremely high standard of presentations and was chaired by Prof Aaron Peace and Prof Tom Kiernan.

The evening saw four presentations: Dr Jack Laffan on the topic ‘It’s stuck

again: Retrieval of a retrograde equipment lodged in a vein graft during CTO angioplasty’; Dr Angela McInerney on ‘IVUS-guided management of iatrogenic right coronary artery dissection’; Dr William Gibson and Dr Stephen O’Connor on ‘Transcatheter aortic valve implantation reverses haemolytic anaemia in the setting of previous transcatheter mitral paravalvular leak closure’; and Dr Christopher Balfe on ‘A narrow escape from a coronavirus Covid-19 mimic: First presentation of severe mitral stenosis and pneumonia during the coronavirus pandemic’.

The judging panel noted the high standard of all the presentations and decided that the winner was Dr Angela McInerney. “The originality and complexity of these cases was fantastic and there was great educational content in all the presentations,” said Prof Aaron Peace in his closing remarks.

It was also announced at the meeting that the recipient of the 2020 Brian McGovern Scholarship was Dr Sean Fitzgerald. The organisers commented: “We were very fortunate this year, thanks to the continued support of Daiichi Sankyo, to be in position to award the Brian McGovern Scholarship once again and I am delighted to announce that the 2020 Brian McGovern Recipient is Dr Sean Fitzgerald,” said the ICS in an announcement.

“Dr Fitzgerald has recently commenced an lnterventional Cardiology Fellowship at the Heart Centre Leipzig at the University of Leipzig, Germany, comprising both clinical and research components under the supervision of Prof Helger Thiele and we look forward to receiving his update at next year’s meeting.”

Volume 7 | Issue 4 | 2021 | Cardiology 8

Prof Jim Crowley

The originality and complexity of these cases was fantastic and there was great educational content in all the presentations

Perspectives on heart failure

Due to the virtual nature of the 2020 ICS Scientific Meeting, attendance was increased compared to previous years and delegates had access to oral abstracts, general posters and moderated posters that covered all aspects of cardiology, from valve replacement and balloon angioplasty, to cardiac toxicity and hypertension, as well as a range of other specialist subjects.

Several abstracts and posters also presented data on various aspects of heart failure (HF). One of the poster presentations by Drs Ronan Cusack, Avinash Radhakrishna and John Barton of the Department of Cardiology at University Hospital Galway was titled ‘Treatment of heart failure in 2020: CHAMPs or chumps?’

The authors conducted an audit of prescribing trends in a tertiary referral centre at University Hospital Galway, within a specialist-led heart failure outpatient clinic service “to evaluate our performance in comparison to these large studies”. In their conclusion, the authors noted: “Despite the strong body of evidence underpinning GDMT, gaps in prescribing habits still exist with specialist heart failure outpatient services.”

They observed that despite compelling evidence, there is low usage of SGLT2 inhibitors and this “is likely explained in part [due] to the lack of established guidelines on its optimal use within treatment algorithms. We would expect this to be addressed in the next update to the European Cardiology Society (ESC) Guidelines for Acute and Chronic Heart Failure.”

Another poster presentation entitled ‘A review of patients with heart failure with mid-range ejection fraction (HFmrEF): Comorbidities and outcomes’ was delivered by researchers from the Department of Cardiology, St James’s Hospital, Dublin.

The researchers sought to compare the comorbidities of HFmrEF patients with those of HFpEF and HFrEF patients, and aimed to compare hospitalisations for acute decompensation HF, and mortality between these groups. The participants comprised 286 new patients referred to one of three HF clinics. In their

higher proportion of devices in the HFrEF group.

“Mortality was similar across the three groups over our followup period of 17.5 months, and there was no difference in mean hospitalisations for ADHF between the groups. In our catchment area, our HFmrEF have a similar phenotype to our HFpEF and HFrEF cohorts.”

Among the other presentations focused on HF was an oral presentation by Ms Loreena Hill, Lecturer in the School of Nursing and Midwifery at Queen’s University Belfast, on ‘Heart failure patient and caregiver needs and expectations regarding self-management via digital health – the PASSION-HF project’. Ms Hill and colleagues sought to assess the needs and requirements of HF patients and their informal caregivers in regard to a virtual doctor. The study was conducted against the backdrop that HF healthcare services are not sufficient to meet the needs of an ageing population with increasing comorbidities and disease complexity, together with the unequal distribution of medical care in rural and urban regions. Taken together, these factors have resulted in an imminent need to identify alternative healthcare approaches, said Ms Hill.

conclusion, the authors wrote: “In our cohort of annual referrals to our three HF clinics, comorbidities were similar in HFmrEF as compared with HFpEF and HFrEF, aside from previous CABG surgery (in which there were fewer in HFmrEF as compared with HFpEF and HFrEF) and HTN (of which there were more in HFpEF). There was a numerically

Using an exploratory mixed-method study within The Netherlands, UK, Ireland, and Germany, qualitative, guided interviews were supplemented by a standardised questionnaire in the study. In their conclusions, the authors wrote: “Patients want reassurance 24/7, independently of the availability of healthcare services, combined with personalised medical advice regarding day-to-day management of their HF. In a next step, we are planning a multi-centre clinical trial to test the first prototype of the e-health product (DoctorMe).”

9 Cardiology | Volume 7 | Issue 4 | 2021

Despite the strong body of evidence underpinning GDMT, gaps in prescribing habits still exist with specialist heart failure outpatient services

Putting together the pieces of the cardiology ‘jigsaw’

Closing the 2020 meeting, outgoing ICS President Prof Jim Crowley told the attendees: “It has been both an honour and a privilege to serve my term as President of the ICS. This last year has been unprecedented because of the pandemic and has brought a lot of challenges to the Society, but I think the Society has performed an important role in helping both my colleagues as consultants, and also the trainees in responding to the pandemic. The Society has helped in continuing to highlight the cardiology needs of society in general and I hope this is going to be a continuing role for the Society in years to come.”

Prof Crowley continued: “We remain committed to supporting members and expanding our work and my sincere thanks goes to every member of the board, and indeed many of my colleagues over the past two years, for giving their support, engagement and free time to this organisation. It is now my great pleasure to hand over to Prof Vincent Maher, who will guide the Society for the next two years until 2022.”

Prof Maher closed-out the meeting by expressing his hopes for the immediate future of the Society and he paid tribute to the outgoing President and council, also revealing the incoming members who will serve on it for the next two years. “This is a great honour,” said Prof Maher. “I’m really feeling privileged to be the President of this wonderful Society and I feel like I am standing on the shoulders of giants… these are very challenging times and I am so proud of everyone’s work in producing this great conference.”

Benefits and drawbacks

Prof Maher also touched on the drawbacks and benefits of having the meeting on a virtual basis. “While we miss our social

interactions, there have been many advantages from having the virtual events and hopefully, this time next year we may have a combination of that, or at least get back to some of the previous interactions we had,” he said.

Describing Prof Crowley as a “wonderful leader”, Prof Maher said: “These are unprecedented times and you, together with [Prof] Albert [McNeill] and [Prof] Ken [McDonald], brought us the Mayo Clinic experience [joint conference], you also improved our financial regulation, brought us towards full charitable status – and I am delighted that you will still be on the council to help us complete that – and you have given us a new website, so you will be a very tough act to follow.”

Prof Maher also paid tribute to Ms Barbra Dalton, Executive Administrator for the ICS and organiser of the conference: “Barbra has been such a special person for the Society,” he said. “Without your energy, enthusiasm and work ethic, we would not be as good as we are. You have worked tirelessly for the smooth running, growth and development of our Society, and for the trainees you have been like a family member.”

He also paid tribute to the work of Prof Aaron Peace and Dr Lana Dixon while they served as council members and he welcomed the new members, who include Prof Crowley; Secretary Prof Brendan McAdam; Treasurer Dr Carl Vaughan; Dr Patricia Campbell, Assistant Secretary; Dr Angie Brown, Irish Heart Foundation representative; Dr Ross Murphy and Dr Briain MacNeill as NSD representatives; and he also warmly welcomed council members Dr Deirdre Ward, Dr Christine Hughes, Mr Alastair Graham, Dr Stephen O’Connor, and Dr Peter McKavanagh. “I am honoured to work with such a strong committee,” said Prof Maher.

‘Great picture’

Referring to Covid-19 lockdowns, Prof Maher said one of the activities he and his family used to pass the time included completing jigsaw puzzles. “In a jigsaw, every piece has a different shape, size, and image, but when you put them all together, you get a great picture.

“Likewise, in cardiology, whether you are responsible for ensuring the quality of a diagnostic test, making a complex management decision, guiding a patient through self-directed treatment adjustment, performing a skilled, complex intervention or operation, or advising on the latest therapeutic or device – everybody is part of this cardiovascular health initiative. As with a jigsaw, every piece counts and every person is needed.”

Prof Maher said he hoped the new ICS website and enhanced connectivity would help to connect all of Ireland’s cardiovascular talent, both at home and abroad. “Reaching out to the Diaspora will enhance our knowledge, help research collaboration and increase opportunities for our trainees.”

Prof Maher added: “We are all aware that cardiological disease processes progress for years before their final complications. Understanding, for example, how valves thicken, hearts stiffen, conduction systems weaken, and atherosclerosis progresses – the more we understand and the more we can intervene and delay these processes, the more we may even reverse the disease in some instances. I hope someday we may have a symposium to address these issues.”

Finally, Prof Maher acknowledged the role of industry in the conference, “without whom we would not be able to do this… and I hope that we will enjoy better times in the future to interact.”

Volume 7 | Issue 4 | 2021 | Cardiology 10

THE POWER TO ACCOMPLISH MORE

Multiple benefits * Proven protection †

JARDIANCE is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise 1 - as monotherapy when metformin is considered inappropriate due to intolerance

- in addition to other medicinal products for the treatment of diabetes

The most prescribed SGLT2i in Ireland 3

* In addition to glucose lowering, JARDIANCE demonstrated reduction in weight and blood pressure vs placebo; JARDIANCE is not indicated for weight loss or reduction of blood pressure.1

† EMPA-REG OUTCOME® was a randomised, double-blind, placebo-controlled cardiovascular outcomes trial. Patients were randomised to receive either JARDIANCE 10 mg once daily, JARDIANCE 25 mg once daily or placebo, on top of standard of care. Primary endpoint was 3-point MACE: Time to first occurrence of cardiovascular death, non-fatal MI, non-fatal stroke. 14% relative risk reduction for combined endpoint of cardiovascular death, non-fatal MI, or non-fatal stroke (ARR 1.6%). 2

References

1. JARDIANCE (empagliflozin) Summary of Product Characteristics 2019. Available at: http://www.medicines.ie/medicine/16081/SPC/Jardiance+10+mg+and+25+mg+Film-Coated+Tablets

2. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-2128. (& Supplementary Appendix)

3. Data on File. Boehringer Ingelheim

Prescribing Information (Ireland) JARDIANCE® (empagliflozin)

Film-coated tablets containing 10 mg or 25 mg empagliflozin. Indication: Jardiance is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise: as monotherapy when metformin is considered inappropriate due to intolerance; in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, refer to the Summary of Product Characteristics. Dose and Administration: The recommended starting dose is 10 mg once daily. In patients tolerating empagliflozin 10 mg once daily who have eGFR ≥ 60 ml/min/1.73 m2 and need tighter glycaemic control, the dose can be increased to 25 mg once daily. The maximum daily dose is 25 mg. When used with sulphonylurea or insulin a lower dose of these may be considered to reduce the risk of hypoglycaemia. Renal impairment: The glycaemic efficacy is dependent on renal function. No dose adjustment is required for patients with an eGFR ≥60 ml/ min/1.73 m2 or CrCl ≥60 ml/min. Do not initiate in patients with an eGFR <60 ml/min/1.73 m2 or CrCl <60 ml/min. In patients tolerating empagliflozin whose eGFR falls persistently below 60 ml/min/1.73 m2 or CrCl below 60 ml/min, the dose of empagliflozin should be adjusted to or maintained at 10 mg once daily. Discontinue when eGFR is persistently below 45 ml/ min/1.73 m2 or CrCl persistently below 45 ml/min. Not for use in patients with end stage renal disease (ESRD) or on dialysis. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Not recommended in severe hepatic impairment. Elderly patients: No dose adjustment is recommended based on age. In patients 75 years and older, an increased risk for volume depletion should be taken into account. Not recommended in patients 85 years or older. Paediatric population: No data are available. Method of administration: The tablets can be taken with or without food, swallowed whole with water. If a dose is missed, it should be taken as soon as the patient remembers; however, a double dose should not be taken on the same day. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Rare cases of diabetic ketoacidosis (DKA), including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including empagliflozin. Consider the risk of DKA in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness and assess patients for ketoacidosis immediately, regardless of blood glucose level. In patients where DKA is suspected or diagnosed, treatment should be discontinued immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with empagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating

empagliflozin, consider factors in the patient history that may predispose to ketoacidosis. Use with caution in patients who may be at higher risk of DKA. Jardiance should not be used for treatment of patients with type 1 diabetes. Renal impairment: See under Dose and Administration; Monitor renal function prior to initiation and at least annually. Cases of hepatic injury have been reported with empagliflozin in clinical trials. A causal relationship between empagliflozin and hepatic injury has not been established. Haematocrit increase was observed with empagliflozin treatment. Osmotic diuresis accompanying therapeutic glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or patients aged 75 years and older. In case of conditions that may lead to fluid loss (e.g. gastrointestinal illness), careful monitoring of volume status and electrolytes is recommended. Temporary interruption of treatment with empagliflozin should be considered until the fluid loss is corrected. Elderly: See under Dose and Administration; special attention should be given to volume intake of elderly patients in case of co-administered medicinal products which may lead to volume depletion (e.g. diuretics, ACE-inhibitors). Temporary interruption of empagliflozin should be considered in patients with complicated urinary tract infections. Cases of necrotising fasciitis of the perineum (Fournier’s gangrene), have been reported in patients taking SGLT2 inhibitors. This is a rare but serious and potentially lifethreatening event that requires urgent surgical intervention and antibiotic treatment. Patients should be advised to seek medical attention if they experience a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware that either uro-genital infection or perineal abscess may precede necrotising fasciitis. If Fournier’s gangrene is suspected, Jardiance should be discontinued and prompt treatment should be instituted. An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies with another SGLT2 inhibitor, counsel patients on routine preventative footcare. Experience in New York Heart Association (NYHA) class I-II is limited, and there is no experience in clinical studies with empagliflozin in NYHA class III-IV. Due to its mechanism of action, patients taking Jardiance will test positive for glucose in their urine. The tablets contain lactose and should not be used in patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.

Interactions: Use with diuretics may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues may increase the risk of hypoglycaemia therefore, a lower dose of insulin or an insulin secretagogue may be required. The effect of UGT induction (e.g. induction by rifampicin or phenytoin) on empagliflozin has not been studied. Co-treatment with known inducers of UGT enzymes is not recommended due to a potential risk of decreased efficacy. If an inducer of these UGT enzymes must be co-administered, monitoring of glycaemic control

to assess response to Jardiance is appropriate. Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by coadministration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide and hydrochlorothiazide. Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives. Fertility, pregnancy and lactation: There are no data from the use of empagliflozin in pregnant women. As a precautionary measure, it is preferable to avoid the use of Jardiance during pregnancy. No data in humans are available on excretion of empagliflozin into milk. Jardiance should not be used during breast-feeding. No studies on the effect on human fertility have been conducted for Jardiance. Undesirable effects: Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be estimated from the available data). Very common: hypoglycaemia (when used with sulphonylurea or insulin). Common: vaginal moniliasis, vulvovaginitis, balanitis and other genital infections, urinary tract infection (including pyelonephritis and urosepsis), thirst, pruritus (generalised), rash, increased urination, serum lipids increased. Uncommon: urticaria, volume depletion, dysuria, blood creatinine increased/glomerular filtration rate decreased, haematocrit increased. Rare: DKA. Not known: necrotising fasciitis of the perineum (Fournier’s gangrene), angioedema. Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes: 10 mg; 28 tablets, 25 mg: 28 tablets. Legal category: POM. MA numbers: 10 mg/28 tablets EU/1/14/930/013; 25 mg/28 tablets EU/1/14/930/004.

Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, D-55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Additional information is available on request from Boehringer Ingelheim Ireland Ltd, The Crescent Building, Northwood, Santry, Dublin 9. Prepared in October 2020

Adverse events should be reported. Reporting forms and information can be found at https://www.hpra.ie/homepage/about-us/report-an-issue. Adverse events should also be reported to Boehringer-Ingelheim Drug Safety on 01 2913960, Fax: +44 1344 742661, or by e-mail: PV_local_UK_Ireland@ boehringer-ingelheim.com

PC-IE-101224 Date of preparation: April 2021 In the management of type 2 diabetes 1

Mater Private Cardiology Masterclass for GPs

Mater Private Network hosted a Cardiology

Masterclass webinar for GPs on 20th March, which featured presentations from a number of its leading cardiologists on the latest diagnostic and management approaches across a range of cardiology topics. The Masterclass was opened by Prof Robert Byrne, Director of Cardiology at Mater Private Hospital, Dublin, and Chair of Cardiovascular Research at the RCSI.

Session One

The first speaker of the Masterclass was Dr Barry Hennigan, Consultant Cardiologist, Mater Private Cork, who discussed ‘Diagnosis and treatment of ischaemia with nonobstructed coronary arteries (INOCA)’, specifically coronary microvascular dysfunction and coronary vasospasm (vasomotor disorders).

INOCA leads to impaired quality-of-life, repeated hospitalisations, unnecessary coronary angiography, and adverse cardiovascular outcomes in the short- and long-term. “There is no silver bullet for microvascular disease. The treatment of these patients is complex and difficult,” Dr Hennigan commented. There remains a lack of randomised controlled trials (RCTs) and knowledge gaps, but correct diagnosis does improve quality-of-life, he maintained.

Angina pectoris is the most common symptom of ischaemic heart disease, and it is very useful to grade the type of angina in presenting patients, Dr Hennigan stated, citing the Canadian Cardiovascular Society classification of angina severity scale.

He added that anatomy is not sufficient for assessing these patients; physiology also needs

to be looked at. “Which is where fractional flow reserve (FFR) comes in. So this is a very user friendly way of rapidly assessing coronary physiology.”

Vasomotor disorders are common in patients with angina and negative coronary angiography; 39 per cent patients with suspected angina and/or positive stress test have non-obstructive coronary artery disease (CAD), Dr Hennigan said. The incidence is also higher among women (approximately 50-to-70 per cent), compared to men (30-to-50 per cent). Coronary microvascular dysfunction (CMD) is key and there is an epicardial vasomotor dysfunction prevalence of 10-to-50 per cent. Coronary vasospasm should be a differential, he noted.

Cardiologist, Mater Private Hospital, Dublin, and Clinical Lead for Acute Coronary Syndrome (ACS), HSE Dublin North East, who spoke about ‘ACS – Where are we now?’

Looking at STEMI versus non-STEMI ACS, Prof Blake said: “As long as that artery is blocked the patient has a mild MI so our task is to open the artery immediately in STEMI, whereas in non-STEMI we can wait a day or two, start anticoagulants, antiplatelet drugs, and then do the angiogram.”

He said the data unequivocally shows that STEMI patients do better with primary percutaneous coronary intervention (PCI) within the target of <120 minutes; “they have less re-infarction, less disabling stroke and they don’t get thrombolysed, and this results in less death.”

In relation to treatment, Dr Hennigan said that lifestyle (weight, diet, stress, smoking cessation) and risk factor (dyslipidaemia, hypertension, and diabetes) management is important, while drug choices include calcium channel blockers, beta-blockers, nitrates, etc depending on sub-category; as outlined in the 2020 expert consensus document organised by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), as well as the 2019 European Society of Cardiology (ESC) angina algorithm.

The next speaker in this session was Prof Gavin Blake, Consultant Interventional

In the HSE north east, the Mater Misericordiae University Hospital (MMUH) is the hub for STEMI, with Prof Blake treating approximately 400 STEMI patients a year. The hospital works closely with the National Ambulance Service to immediately triage the patients to the Mater Cath lab if a STEMI is picked up. This has resulted in an increase in the number of patients arriving to the Cath lab via direct ambulance transfer from 42-to-58 per cent (2013-2020), with almost 80 per cent of MMUH PPCIs being carried out within the time target, he reported.

ACS prevention/recurrence wise, LDL cholesterol reduction is key; “the lower you get your LDL, the better you do. If you get it well below 0.8 and keep it there, then the mantra ‘lowest for longest’ is best,” Prof Blake emphasised.

The third speaker of this session was

Volume 7 | Issue 4 | 2021 | Cardiology 12

Prof Robert Byrne

The hospital works closely with the National Ambulance Service to immediately triage the patients to the Mater Cath lab if a STEMI is picked up

Prof Gavin Blake

Prof Gábor Széplaki, Head of Cardiac Electrophysiology at the Mater Private Hospital, Dublin, who discussed ‘What is the role of early intervention for atrial fibrillation (AF)?’

The most important thing to know about AF is that it is a progressive disease, with 20 per cent of patients progressing from intermittent to persistent AF within a year of diagnosis, he said, adding that the longer it persists, the harder it is to treat, and the higher the risk of MI or stroke “so early diagnosis is key”.

Treatment wise, Prof Széplaki cited the ‘ABC pathway’:

 A - anticoagulation/avoid stroke;

 B - better symptom control;

 C - cardiovascular risk factors and concomitant diseases.

AF patents benefit from an integrated care treatment approach, between GPs and cardiologists, which was a key reason behind the setting up of the Mater Private Atrial Fibrillation Institute in 2020, Prof Széplaki explained. The Institute consists of a multidisciplinary AF management team, providing access to advanced/complex therapies and lifestyle and risk factor modification in close collaboration with GP practices, and is also a clinical research centre for AF.

The role of catheter ablation in AF is increasing, he noted, highlighting multiple positive studies (eg, ATTEST, EAST-AFNET 4, CASTLE AF trial, etc). The Institute carries out about 700 catheter ablation procedures a year, the majority (500) for AF.

Session Two

The first speaker of the second session was Dr Ronan Margey, Clinical Director, Cardiology Clinical Lead, Mater Private Cork, who discussed ‘Structural heart disease – What’s new in TAVI’.

Dr Margey outlined how transcatheter aortic valve implants (TAVI) have rapidly evolved over the last 15 years, now being widely accepted as the standard of care for symptomatic aortic stenosis, with a robust

supportive clinical trial evidence base behind the procedure.

Aortic stenosis is a disease of age, and there was previously a treatment gap with many older patients not being deemed suitable for surgery, so TAVI has filled that gap very well, as a safe and effective procedure, with low complication rates and quick recovery time, he said.

“Surgery should only be performed in this age group [over 75s] if there is some contraindication to TAVI.” In people under 65, Dr Margey said surgery remains the first-line, whereas in patients aged between 65-to-75 years it can be either option and should be based on shared decision making between the cardiology team and the patient.

TAVI outcomes continue to improve over time as valve designs and surgical techniques refine and evolve, he noted. “The evolution over the last decade has been remarkable and we can now treat a wider range of patients, and pick and choose different valves, to optimise the results for specific individuals.”

Following TAVI, most patients can be treated with aspirin alone, he said, quoting the latest trial data, “unless they have an indication for oral anticoagulant therapy.”

The application of transcatheter technology to treat other valvular heart diseases is also under rapid evaluation, Dr Margey concluded.

The next speaker was Dr John Keaney, Consultant Cardiologist/Electrophysiologist, Mater Private Hospital, Dublin, who addressed ‘ECG interpretation: Tips and tricks’, focusing on ECG in patients with arrhythmia; evaluation of Long QT; palpitations/AF, and bundle branch and fascicular blocks.

Long QT syndrome (LQTS), which occurs in one-in-2,000 people, is important to diagnose as it is associated with sudden

cardiac death secondary to fatal ventricular arrhythmias, he explained. However, there is significant overlap; 15 per cent of the general population may have a QTc in the ‘borderline’ range. On the other hand, however, 25-to-35 per cent of patients harbouring a LQTS-causing mutation have a QTc. Great intra-observer variability exists in QTc measurement he added.

Bifascicular block is often associated with structural heart disease (50-to-80 per cent) and extensive fibrosis of the conducting system. There is a risk of progression to complete heart block with additional damage to the third remaining fascicle, however, clinical context is important, as the overall rate of progression to complete heart block is 1-to-4 per cent per year, Dr Keaney noted.

The final speaker of this session was Dr Róisín Colleran, Consultant Interventional Cardiologist, Mater Private Hospital, Dublin, who discussed ‘Hot topics in the management of hypertension’.

She noted that hypertension is under-recognised, under-treated and poorly controlled in Ireland, as proved by Ireland performing poorest across all parameters in a study of hypertension in 12 high-income countries. Improving detection of hypertension is thus key, stressed Dr Colleran, highlighting how home BP monitoring has been shown to be more reliable than office or 24-hour BP in this regard, and correlates better with LV mass index.

Treatment initiation wise, the 2018 ESC/ESH hypertension guidelines outline the latest evidence-based approaches. Compared to the 2013 guidelines, the thresholds for initiation of treatment are lower than before, she pointed out: Treatment is recommended even for high normal BP (130-139/80-89) in high-risk patients, including with anti-hypertensive

13 Cardiology | Volume 7 | Issue 4 | 2021

Dr Ronan Margey Dr Róisín Colleran

therapy, while lifestyle modification remains key across all grades.

There are five main classes of first-line antihypertensives, which have roughly an equivalent effect on reducing CV events and mortality, but therapy should be tailored according to individual patient risk, noted Dr Colleran. “Treatment initiation [for uncomplicated hypertension] with dualtherapy, rather than mono therapy, is recommended in most cases, preferably with a single combined pill, and for patients whose BP is uncontrolled on this combination, a triple combination is recommended, again in a single pill if at all possible, and for patients with resistant hypertension despite this therapy, a second-line agent should be added.”

Official BP treatment targets are also now tighter than before: <130/80mmHg in patients <65 years (SBP ≥120), and <140/80 mmHg in patients >65 years, she outlined.

There is renewed interest in renal denervation as a treatment option of resistant hypertension, but device therapies for hypertension are no longer recommended under the 2018 ESC/ESH guidelines, pending further evidence, Dr Colleran concluded.

Session Three

The first speaker of this session was Dr Emily Ho, Consultant Cardiologist, Mater Private Hospital, Dublin, who looked at ‘Risk stratification for coronary artery disease – the role of CT angiogram’.

“With advancements in cardiac imaging, particularly with cardiac CT, we can now detect not just the obstructive lesions, but also subclinical disease which would allow us to implement primary prevention measures at an earlier timepoint,” she said, explaining how the last decade has seen a “paradigm shift from functional testing to anatomical testing in this context”.

The two types of cardiac CT are coronary artery calcium (CAC) score and CT coronary angiogram. The CAC score has been shown to be a strong independent predictor of cardiovascular risk, and outperforms traditional risk factors, said Dr Ho. It is a powerful marker of coronary atherosclerosis and risk predictor for atherosclerotic cardiovascular disease events, and should be used to guide risk modification management, as per the guidelines and consensus statements. CAC is most suited to asymptomatic intermediate-risk patients, and low-risk patients with modifier factors, she said. While it is used to guide risk modification and management in these patients, there is no RCT data for CAC scoreguided primary prevention yet, but one is coming soon (SCOT HEART 2). It should also be noted that CAC score alone is not sufficient for symptomatic individuals, Dr Ho pointed out.

In relation to CT coronary angiography, Dr Ho said it should be used as the firstline investigation in symptomatic low (modifiers) and intermediate probability patients, with chest pain. “Its greatest strength is in its negative predictive value, which is >95 per cent, so if you have a normal CT angiogram you do not have coronary artery disease.”

It also gives useful data on plaque morphology and the extent and location of lesions/degree in stenosis, thus CT angiography helps directs risk management therapies and interventions, positively impacting cardiovascular outcomes, she concluded.

The final speaker of the day was Prof Robert Byrne, who gave an ‘Update on coronavirus and heart disease’. He noted that multiple data sources have documented increased risk of death or ICU admission in CAD patients who contract Covid-19. Increased expression of ACE-2 in patients with CVD underlies this increased risk of severe illness, though much remains to be learned, he acknowledged.

A significant proportion of patients with

SARS-CoV-2 infection show evidence of acute myocardial injury (10-to-30 per cent of hospitalised Covid-19 patients) and this portends worse prognosis. “Troponin should be routinely assessed in patients with Covid-19 to optimise risk stratification and subsequent treatment strategies,” stated Prof Byrne.

The pathogenesis of acute myocardial injury is multifactorial, though there is accumulating evidence pointing to microvascular thrombosis as a dominant injury mechanism, he reported. Renin-angiotensin-aldosterone system antagonists do not appear to be associated with adverse outcome in Covid-19, Prof Byrne summarised, quoting the latest data.

Observational data suggests a relatively high rate of abnormal myocardial signal on CMR in patients who recover from acute Covid-19 though its clinical significance is still unclear and replication studies are awaited, he acknowledged. To understand and address these particular issues, Prof Byrne is leading the Study of heart disease and immunity after Covid-19 in Ireland (SETANTA), a multicentre, prospective, community-based, cross-sectional study of cardiac complications and haematological abnormalities in patients recovered post-Covid 19. The study, which is currently recruiting patients, is scheduled to conduct 12 months follow-up and be completed in June 2022.

Questions

Each session was followed by a panel discussion/Q&A, which were moderated by Dr Maria Horgan, GP, Ballincollig, Cork, and Dr Roisin Lyons, GP, Navan Road, Dublin. Numerous questions were put to the expert panel, including when to initiate particular therapies, what diagnostic tests should be ordered for particular patients, and what procedure would be advised for certain ages, etc. Attendees were also provided with the speaker presentations after the event.

The Cardiology Masterclass was approved for three CPD points and 0.5 GMS study leave, with further details on this and future events available from: events@materprivate.ie

Volume 7 | Issue 4 | 2021 | Cardiology 14

Dr Emily Ho

Atrial fibrillation: An overview

AUTHOR: Theresa Lowry-Lehnen, CNS, GPN, RNP and Associate Lecturer at Institute of Technology Carlow

Atrial fibrillation (AF) is the most common cardiac arrhythmia diagnosed in clinical practice and affects more than 33 million people worldwide. Characterised by the rapid and irregular beating of the atrial chambers of the heart, episodes of which may become longer or continuous over time, AF is associated with a significant risk of transient ischaemic attack, ischaemic stroke, systemic embolism, and death. While not immediately life-threatening like some cardiac arrhythmias, AF carries a five-fold higher risk of stroke caused by the formation of blood clots in the heart and blocked blood vessels in the brain. The percentage of people with AF increases with age with 0.1 per cent under 50 years, 4 per cent between 60-to-70 years and 14 per cent over 80 years of age being affected. Due to increased lifespan, AF is on the rise and predicted to affect 14-to-17 million people in Europe by 2030, with 120,000-to-215,000 new cases per year (estimated incidence 0.23-0.41 per 1,000 person/years). A further estimated 280,000-to-340,000 new ischaemic strokes, 3.5-to-four million hospitalisations for AF and 100-to-120 million outpatient visits can also be added to these figures. AF constitutes a significant public health challenge with high comorbidity and increased mortality risk and is a significant cause of increasing healthcare costs globally. An estimated 1.4 per cent of all adults over 65 years are living with undiagnosed AF, which means more cases of unmanaged AF will create even further economic strain on our healthcare systems.

Aetiology

AF is multi factorial in nature.

Abnormalities or damage to the heart’s structure are the most common causes. AF is more common with increased age and affects certain groups of people more than others. While it can sometimes affect people who are physically very fit, AF is more common in people with other heart conditions

such as hypertension, atherosclerosis, cardiomyopathy, pericarditis, heart valve and congenital heart disease. A family history of AF may also increase the risk. AF is also associated with other medical conditions, such as pneumonia, lung cancer, pulmonary embolism, sarcoidosis, obstructive sleep apnoea, hyperthyroidism and obesity. A number of triggers are associated with the condition, including smoking, excessive alcohol and coffee consumption. When no other medical conditions are associated with it, it is called lone AF.

Symptoms

AF is often asymptomatic, especially in the elderly, but many patients experience palpitations, rapid and irregular heartbeat, vague chest discomfort or symptoms of heart failure, such as weakness, light-headedness, and dyspnoea, particularly when the ventricular rate is very rapid (140 to 160 beats/minute). Patients may also present with signs and symptoms of acute CVA or other organ damage due to systemic emboli.

Diagnosis and screening

Diagnostic investigation of AF typically includes a complete medical history and physical examination, ECG, full

blood count, urea and electrolytes, and serum thyroid stimulating hormone level. All patients who present with symptoms of AF should have at minimum their pulse checked for irregularities as well as a 12-lead ECG.

ECG findings for AF indicate the absence of P waves, irregularly irregular R-R intervals and the presence of F (fibrillatory) waves between the QRS complexes. Fibrillatory waves are irregular in timing and morphology with baseline undulations at rates up to or >300/minute, best seen in lead V1 and not always apparent in all leads.

Other diagnostic tests for AF include CXR and echocardiogram. Echocardiography is carried out to assess for structural heart defects such as left atrial enlargement, left ventricular wall motion abnormalities suggesting past or present ischaemia, valvular disorders and cardiomyopathy, and to identify additional risk factors for stroke such as atrial blood stasis, thrombus or complex aortic plaque. Atrial thrombi are more likely in the atrial appendages, where they are best detected by transoesophageal rather than transthoracic echocardiography.

15 Cardiology | Volume 7 | Issue 4 | 2021

First diagnosed AF Every patient who presents with AF for the first time irrespective of the duration or the presence and severity of AF-related symptoms

Paroxysmal AF AF that terminates spontaneously, usually within 48 hours, although AF paroxysms may continue for up to seven days. After 48 hours spontaneous conversion is low and anticoagulation must be considered

Persistent AF Continuous AF sustained for more than seven days or requires termination by cardioversion, either with drugs or by direct current cardioversion

Longstanding persistent AF

Continuous AF of greater than 12 months duration. It is usually decided to adopt a rhythm control strategy at this stage

Permanent AF Permanent AF is said to exist when the presence of the arrhythmia is accepted by the patient and physician. Rhythm control interventions, by definition, are not pursued in patients with permanent AF

AF is a progressive disorder. The exact electro-pathological mechanisms underlying persistence of AF are at present unknown and none of the available recording techniques can determine the degree and extensiveness of atrial electropathology or determine the stage of the condition at any time in the process. Identifying individuals at risk of developing AF is important, however, as there is strong evidence that early detection and treatment of modifiable risk factors can reduce morbidity and mortality.

Classification of AF

The European Society of Cardiology (ESC) distinguishes five types of AF based on presentation and duration of arrhythmia (Table 1).

Complications of AF

The absence of atrial contractions in AF predisposes the patient to thrombus formation. Risk of stroke is higher in older patients and in those with mechanical heart valves, rheumatic valvular disease, hyperthyroidism, hypertension, diabetes, left ventricular systolic dysfunction, or previous thromboembolic events. Systemic emboli can also cause malfunction or necrosis of other organs. AF may impair cardiac

output. Loss of atrial contraction can lower cardiac output at normal heart rate by about 10 per cent. Such a decrease is usually well tolerated except when the ventricular rate becomes too fast (>140 beats/minute), or when patients already have borderline or low cardiac output. In such cases, cardiac failure may develop.

Treatment

Treatment of AF varies from person to person and depends on the type of AF, symptoms, treatment of any underlying cause, age, and overall health. The first step is to try to find the cause of the

AF. For example, hyperthyroidism can sometimes be the underlying cause of AF and medication to control the condition can correct the symptoms of AF. If no underlying cause is found, treatment of AF is usually aimed at either rhythm or rate control. Since AF induces electrical, structural, and contractile remodelling, therapy aimed at prevention or restoration of remodelling and consequently restoration of sinus rhythm should be the first choice strategy. The different AF treatment modalities include pharmacological therapy, electrical cardioversion, pacemaker implantation combined with His bundle ablation or surgical isolation of the pulmonary veins with or without additional linear lesions/ substrate modification.

Anti-arrhythmic medication can control AF by restoring normal heart rhythm and controlling the rate at which the heart beats. The choice of antiarrhythmic depends on the type of AF, comorbidities, side effects of the medicine chosen and response to therapy. Some patients may need more than one antiarrhythmic to control AF and a variety of medications are available to restore normal heart rhythm. The aim is to reduce the resting heart rate to <90 beats per minute, however, in some people the target is <110bpm.

First-line medications include beta blockers such as propranolol or atenolol and nondihydropyridine calcium channel blockers such as diltiazem or verapamil, which slow the conduction of impulses to the ventricles. Digoxin may be added to control the heart rate further. Digoxin is usually only effective for controlling the ventricular rate at rest and should therefore only be used as a monotherapy in predominantly sedentary patients.

Anti-arrhythmic drugs can be classified clinically into those that act on supraventricular arrhythmias (eg, verapamil), both supraventricular and ventricular arrhythmias (eg, amiodarone) and those that act on ventricular

Volume 7 | Issue 4 | 2021 | Cardiology 16

TABLE 1: ESC AF classification Reference: Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology

Risk of stroke is higher in older patients and in those with mechanical heart valves, rheumatic valvular disease, hyperthyroidism, hypertension, diabetes, left ventricular systolic dysfunction, or previous thromboembolic events

YOUR CHOICE FOR AGEING NVAF PATIENTS1

LIXIANA® was developed for a broad range of ageing NVAF patients.1,2 By offering a unique combination of clinical1-3 and practical4,5 benefits, LIXIANA® may help reduce the complexity in managing stroke prevention in your ageing NVAF patients.

DEVELOPED WITH THE AGEING PATIENT IN MIND 1,6,7

LIXIANA® is a once-daily DOAC indicated for: Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA).4

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.4

References: 1. Kato ET et al. J Am Heart Assoc 2016;5(5). pii: e003432. 2. Giuliano RP et al. N Engl J Med 2013;369(22):2093 -2104; and supplementary appendix. 3. Ruff CT et al. Lancet 2015;385(9984):2288 -95. 4. LIXIANA® Summary of Product Characteristics, November 2020. 5. Steffel J et al. Eur Heart J 2018;39:1330 -1393. 6. Steffel J et al. J Am Coll Cardiol 2016;68:1169 -78. 7. Ruff, et al. American Heart Journal 2010; 160 (4): 635-641.

LIXIANA (edoxaban) 60 mg / 30 mg / 15 mg film-coated tablets prescribing information

See Lixiana Summary of Product Characteristics (SmPC) prior to prescribing for full list of adverse events

Presentation: Presentation: 60 mg (yellow) / 30 mg (pink) / 15mg (orange) edoxaban (as tosilate) film-coated tablets. Indications: Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA). Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Posology and method of administration: NVAF:

Recommended dose is 60 mg edoxaban once daily with or without food. Continue therapy long term. VTE: Recommended dose is 60 mg edoxaban once daily with or without food following initial use of parenteral anticoagulant for at least 5 days. Duration of therapy (at least 3 months) should be based on risk profile of the patient. For NVAF and VTE the recommended dose is 30 mg edoxaban once daily in patients with one or more of the following: moderate or severe renal impairment (creatinine clearance (CrCL) 15 - 50 mL/min); low body weight ≤ 60 kg; concomitant use of the P-glycoprotein (P-gp) inhibitors, ciclosporin, dronedarone, erythromycin, or ketoconazole. The 15 mg dose of edoxaban is not indicated as monotherapy, and should only be used during a switch from edoxaban to VKA in certain patients (see SmPC for full details). Edoxaban can be initiated or continued in patients who may require cardioversion. For transoesophageal echocardiogram guided cardioversion in patients not previously treated with anticoagulants, edoxaban should be started at least 2 hours before cardioversion to ensure adequate anticoagulation. Cardioversion should be performed no later than 12 hours after the dose of edoxaban on the day of the procedure. Confirm prior to cardioversion that the patient has taken edoxaban as prescribed. If a dose of edoxaban is missed, the dose should be taken immediately and then continued once daily on the following day. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Clinically significant active bleeding. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Lesion or condition, if considered to be a significant risk for major bleeding including current or recent gastrointestinal (GI) ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage,

known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. Uncontrolled severe hypertension. Concomitant treatment with any other anticoagulants e.g. UFH, low molecular weight heparins, heparin derivatives (fondaparinux, etc.), VKA or DOACs except under specific circumstances of switching oral anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter. Pregnancy and breast-feeding. Special warnings and precautions for use: Haemorrhagic risk: Caution in patients with increased risk of bleeding such as elderly on ASA. Discontinue if severe haemorrhage occurs. The anticoagulant effect of edoxaban cannot be reliably monitored with standard laboratory testing. A specific anticoagulant reversal agent for edoxaban is not available. Haemodialysis does not significantly clear edoxaban. Renal impairment: CrCl should be monitored at the initiation of edoxaban and afterwards when clinically indicated. Not recommended in patients with end stage renal disease or on dialysis. Renal function and NVAF: A trend towards decreasing efficacy with increasing CrCl was observed for edoxaban compared to well-managed warfarin. Edoxaban should only be used in patients with NVAF and high CrCl after a careful benefit risk evaluation. Hepatic impairment: Not recommended in severe hepatic impairment. Caution in mild or moderate hepatic impairment. Caution in patients with elevated liver enzymes (ALT/AST > 2 x ULN) or total bilirubin ≥ 1.5 x ULN. Perform liver function testing prior to initiation and then periodically monitor for treatment beyond 1 year. Surgery or other interventions: discontinue edoxaban as soon as possible and preferably at least 24 hours before the procedure. If procedure cannot be delayed, the increased risk of bleeding should be weighed against urgency of the procedure. Restart edoxaban as soon as haemostasis achieved. Prosthetic heart valves and moderate to severe mitral stenosis: Not recommended. Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Not recommended. Patients with active cancer: Not recommended in treatment and/or prevention of VTE. Patients with a history of thrombosis diagnosed with antiphospholipid syndrome: DOACs including Edoxaban are not recommended. Drug interactions: Concomitant use of the P-gp inhibitors ciclosporin, dronedarone, erythromycin, or ketoconazole requires edoxaban dose reduction to 30mg. Edoxaban should be used with caution with concomitant P-gp inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s Wort). Concomitant high dose ASA (325 mg) or chronic NSAIDs is not recommended. Concomitant

EDX/21/0204

Date of preparation: March 2021

ASA at doses > 100 mg and < 325 mg should be under medical supervision only. Very limited experience with dual antiplatelet therapy or fibrinolytics. Possibility of increased bleeding risk with concomitant SSRIs or SNRIs. Adverse reactions: Common: anaemia, dizziness, headache, epistaxis, abdominal pain, lower GI haemorrhage, upper GI haemorrhage, oral/pharyngeal haemorrhage, nausea, blood bilirubin increased, gamma GT increased, cutaneous soft tissue haemorrhage, rash, pruritus, macroscopic haematuria/urethral haemorrhage, vaginal haemorrhage, puncture site haemorrhage, liver function test abnormal. Serious uncommon: thrombocytopenia, hypersensitivity, intracranial haemorrhage (ICH), intraocular haemorrhage, other haemorrhage, haemoptysis, surgical site haemorrhage. Serious rare: anaphylactic reaction, allergic oedema, subarachnoid haemorrhage, pericardial haemorrhage, retroperitoneal haemorrhage, intramuscular haemorrhage (no compartment syndrome), intra-articular haemorrhage, subdural haemorrhage, procedural haemorrhage. Legal category: POM Package quantities: 60mg / 30mg – 28 tablets. 15mg – 10 tablets. Marketing Authorisation (MA) number: EU/1/15/993/018, EU/1/15/993/005, EU/1/15/993/001 MA holder: Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, 81379 Munich, Germany Additional

Information: Available on request from Daiichi Sankyo Ireland Ltd. Telephone: (01) 489 3000. Fax: (01) 489 3033. Email: medinfo@daiichi-sankyo.ie Date of preparation: Nov 2020 EDX/20/1215

Adverse events and product complaints should be reported. To report an adverse event or a product complaint about a Daiichi Sankyo medicine, please call Daiichi Sankyo Ireland Ltd. on (01) 4893000. Healthcare professionals are also asked to report any suspected adverse reactions to Daiichi Sankyo medicines to HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: (01) 6764971; Fax: (01)6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

arrhythmias (eg, lidocaine). They can also be classified according to their effect on the electrical behaviour of myocardial cells during activity (Vaughan Williams Classification). Class I antiarrhythmic medications are membrane stabilising drugs, eg, lidocaine and flecainide. Class II are beta blockers. Class III include amiodarone and sotalol and Class IV are calcium channel blockers, including verapamil, but not dihydropyridines. The negative inotropic effects of antiarrhythmic drugs tend to be additive. Special care should be taken if two or more are used, especially if myocardial function is impaired. Many medications that are effective in countering arrhythmias can also provoke them in some instances. Patients must be monitored closely as common side-effects of anti-arrhythmic medications include hypotension, fatigue, nausea, vomiting, possible issues with liver, kidneys, thyroid or lungs, and heart rhythm disorders. Amiodarone causes sensitivity to sunlight and skin changes are common, therefore, sun protection is important when taking this medication.

Aspirin is not recommended to prevent strokes caused by AF. Patients with a high or moderate level of risk of stroke or thrombus formation due to AF are usually prescribed an anticoagulant such as the vitamin K antagonist warfarin or a novel oral anticoagulant (NOAC), also called direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban or edoxaban. There are fewer dietary and medication interactions with the newer agents, and less need for monitoring. NOACs are at least as effective or superior to warfarin for stroke prevention in patients with non-valvular AF, and are at least as safe or safer in terms of bleeding risk, according to three large clinical trials. NOACs have major pharmacologic advantages over warfarin, including rapid onset/offset of action, few drug interactions and predictable pharmacokinetics. Practical advantages of NOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation monitoring.

Potential drawbacks include a risk of bleeding that might be increased in patients over 75 years of age, the lack of a routine laboratory test to reliably measure anticoagulant effect, and previously the lack of an antidote for reversal. Choice of NOAC is influenced by the patient’s individual characteristics, including risk of stroke or VTE, risk of bleeding, and comorbidity, in particular renal dysfunction. It is also recommended that one of the bleeding risk scores, such as the HAS-BLED score, be used to help riskassess patients. The choice of agent should take into consideration the patient’s age, weight and creatinine clearance, as dose adjustment may be required.

Cardioversion is a medical procedure carried out in a hospital setting by which a tachycardia or other cardiac arrhythmia is converted to a normal rhythm using an electric current or pharmacology. Synchronised electrical cardioversion uses a therapeutic dose of electric current to the heart at a specific moment in the cardiac cycle, restoring the activity of the electrical conduction system of the heart. Electrical cardioversion has success rates of between 65-to-90 per cent and can be performed safely as a day case procedure. The likelihood of success can be further improved by the co-administration of anti-arrhythmic drug therapy.

Pharmacologic cardioversion, also referred to as chemical cardioversion,

uses anti-arrhythmic medication instead of an electrical shock. Pharmacological cardioversion is often used for the treatment of AF of recent onset. Flecainide, ibutilide, propafenone and vernakalant can be used in patients with no structural heart disease. Where structural heart disease is present, intravenous amiodarone is the drug of choice. Flecainide administered intravenously in patients with AF of recent onset has been shown to restore sinus rhythm in 72-to-95 per cent of patients, with greatest success rates in those who receive treatment within 24 hours of AF onset. When AF has persisted for >48 hours, pharmacological cardioversion is much less likely to be effective. Amiodarone appears to be the most effective agent for restoring sinus rhythm in patients with persistent AF. For patients who have been in AF for longer than 12-to-24 hours, or in whom the duration of the arrhythmia is not clear, a minimum period of anticoagulation of three weeks is recommended before cardioversion. Even if echocardiography has demonstrated no thrombus before cardioversion, patients should be anticoagulated for at least one month post cardioversion, since mechanical atrial function may return slowly after cardioversion.

Catheter ablation has emerged as an important rhythm-control strategy and is an increasingly used option if medical

Volume 7 | Issue 4 | 2021 | Cardiology 18

Clexane Safety Syringe designed to protect against needle stick injuries

Automatic release of the safety mechanism when the plunger is fully depressed

Prescribing Information: Clexane (enoxaparin sodium) & Clexane Forte Solution for Injection in pre-filled syringes Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentations: Clexane® single dose pre-filled syringes containing either: 2,000 IU (20mg) enoxaparin sodium in 0.2ml, 4,000 IU (40mg) enoxaparin sodium in 0.4ml, 6,000 IU (60mg) enoxaparin sodium in 0.6ml, 8,000 IU (80mg) enoxaparin sodium in 0.8ml or 10,000 IU (100mg) enoxaparin sodium in 1ml. Clexane® Forte single dose pre-filled syringes containing either: 12,000 IU (120mg) enoxaparin sodium in 0.8ml or 15,000 IU (150mg) enoxaparin sodium in 1ml. Indications: In adults for: prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular those undergoing orthopaedic or general surgery including cancer surgery; prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at increased risk of venous thromboembolism (VTE); treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require thrombolytic therapy or surgery; prevention of thrombus formation in extracorporeal circulation during haemodialysis; treatment of unstable angina and non ST-segment elevation myocardial infarction (NSTEMI), in combination with oral acetylsalicylic acid; treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be managed medically or with subsequent percutaneous coronary intervention (PCI). Dosage & Administration: Each pre-filled syringe is for single use only. Prophylaxis of VTE in Surgical Patients: With moderate risk of thromboembolism, recommended dose of enoxaparin sodium is 2,000 IU (20mg) once daily by subcutaneous (SC) injection. Initiation 2hrs before surgery was proven effective and safe in moderate risk surgery. Treatment should be maintained for at least 7-10 days whatever the recovery status (e.g. mobility) and should be continued until the patient no longer has significantly reduced mobility. In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU (40mg) once daily by SC injection preferably started 12hrs before surgery. Need for earlier than 12hrs enoxaparin sodium preoperative prophylactic initiation (e.g. high-risk patient waiting for a deferred orthopaedic surgery), the last injection should be administered no later than 12hrs prior to surgery and resumed 12hrs after surgery. For patients undergoing major orthopaedic surgery an extended thromboprophylaxis up to 5 weeks is recommended. For patients with high risk of VTE undergoing abdominal or pelvic surgery for cancer, extended thromboprophylaxis up to 4 weeks is recommended. Prophylaxis of VTE in Medical Patients: Recommended dose of enoxaparin sodium is 4,000 IU (40mg) once daily by SC injection. Treatment with enoxaparin sodium is prescribed for at least 6-14 days. Benefit is not established for treatment longer than 14 days. Treatment of DVT/PE: 150 IU/kg (1.5mg/kg) administered SC once daily should be used in uncomplicated patients with low risk of VTE recurrence. 100 IU/kg (1mg/kg) twice daily should be used in all other patients such as those with obesity, symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis. The regimen should be selected based on individual assessment including evaluation of the thromboembolic risk and risk of bleeding. Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy should be initiated when appropriate. Treatment of Acute Coronary Syndromes: For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 100 IU/kg (1mg/kg) every 12hrs by SC injection administered in combination with antiplatelet therapy. Treatment should be for a minimum of 2 days and until clinical stabilization (usual duration 2 to 8 days). Acetylsalicylic acid recommended for all patients without contraindications at an initial oral loading dose of 150–300mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75–325mg/day long-term. For treatment of acute STEMI, recommended dose of enoxaparin sodium is a single intravenous (IV) bolus of 3,000 IU (30mg) plus a 100 IU/kg (1mg/kg) SC dose followed by 100 IU/kg (1mg/kg) administered SC every 12hrs (maximum 10,000 IU (100mg) for each of the first 2 SC doses). Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75mg to 325mg once daily) should be administered concomitantly unless contraindicated. Recommended duration of treatment is 8 days or until hospital discharge. When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 8hrs before balloon inflation, no additional dosing needed. If the last SC administration was given more than 8hrs before balloon inflation, an IV bolus of 30 IU/kg (0.3mg/

Needle completely covered by the protection shield immediately after the injection

700m+ TREATED WORLDWIDE1

kg) enoxaparin sodium should be administered. During haemodialysis: 100 IU/kg (1mg/kg) enoxaparin sodium introduced into arterial line of the circuit at beginning of dialysis. This dose is usually sufficient for a 4-hour session. If fibrin rings are found, e.g. after a longer session, a further 50 to 100 IU/kg (0.5 to 1mg/kg) may be given. In patients with high risk of haemorrhage reduce the dose to 50 IU/kg (0.5mg/kg) (double vascular access) or 75 IU/kg (0.75mg/kg) (single vascular access). Special Populations: Elderly ≥75 years of age: For treatment of acute STEMI, an initial IV bolus must not be used. Initiate dosing with 75 IU/kg (0.75mg/kg) SC every 12hrs (maximum 7,500 IU (75mg) for each of the first 2 SC doses only, followed by 75 IU/kg (0.75mg/kg) SC dosing for the remaining doses). Paediatric: Safety and efficacy not established. Renal impairment: Dosage adjustment required for patients with severe renal impairment (creatinine clearance 15-30 mL/min). Not recommended for patients with end stage renal disease (creatinine clearance <15 mL/min. Hepatic Impairment: Limited data in this population therefore caution should be used. Contraindications: Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including low molecular weight heparins (LMWH) or any of the excipients. Recent (<100 days) history of immune mediated heparin-induced thrombocytopenia (HIT) or in the presence of circulating antibodies. Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known/ suspected oesophageal varices, arteriovenous malformations, vascular aneurysms/ major intraspinal/ intracerebral vascular abnormalities. Spinal/ epidural/ loco-regional anaesthesia when enoxaparin sodium is used for treatment in the previous 24hrs. Warnings and Precautions: Do not use interchangeably (unit for unit) with other LMWHs. History of HIT (>100 days) without circulating antibodies: Use with extreme caution in these patients and only after careful benefitrisk assessment and non-heparin alternative treatments are considered. Monitoring of platelet counts: There is a risk of antibody-mediated HIT, which is higher in postoperative patients and mainly after cardiac surgery and in patients with cancer. It is recommended that the platelet counts be measured before the initiation of therapy with enoxaparin sodium and then regularly thereafter during the treatment; or if clinical symptoms suggestive of HIT are experienced. Patients must be aware of the symptoms and told to inform their primary care physician if experienced. If a confirmed significant decrease of the platelet count is observed (30-50% of the initial value), enoxaparin sodium treatment must be immediately discontinued, and the patient switched to another nonheparin anticoagulant alternative treatment. Haemorrhage: Use with caution in conditions with increased potential for bleeding (e.g. impaired haemostasis, history of peptic ulcer, recent ischemic stroke, severe arterial hypertension, recent diabetic retinopathy, neuro- or ophthalmologic surgery, concomitant use of medications affecting haemostasis). Laboratory tests: Increases in activated partial thromboplastin time (aPTT) and activated clotting time (ACT) may occur at higher doses but not linearly correlated with increasing enoxaparin sodium antithrombotic activity. Spinal/epidural anaesthesia or lumbar puncture: must not be performed within 24hrs of administration of therapeutic doses of enoxaparin sodium; placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of enoxaparin sodium is low. Skin necrosis and cutaneous vasculitis: have been reported with LMWHs and should lead to prompt treatment discontinuation. Percutaneous coronary revascularization procedures: To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure device is used, the sheath can be removed immediately. If a manual compression method is used, sheath should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma formation. Acute infective endocarditis: Use of heparin is usually not recommended in patients with this condition. Mechanical prosthetic heart valves: Enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients (including in pregnancy) with mechanical prosthetic heart valves. Elderly patients (especially >80 years old): may be at increased risk of bleeding complications at therapeutic doses. Hepatic impairment: Enoxaparin sodium should be used with caution in these patients. In patients with liver cirrhosis dose adjustment based on monitoring of anti-Xa levels is unreliable and

not recommended. Renal impairment: There is an increased risk of bleeding for these patients therefore careful clinical monitoring is advised and biological monitoring by anti-Xa activity measurement might be considered. Enoxaparin sodium is not recommended for patients with end stage renal disease. In patients with severe renal impairment (creatinine clearance 15-30 mL/min) a dosage adjustment is recommended for therapeutic and prophylactic dosage ranges. Low body weight patients: are at increased risk of bleeding at prophylactic and treatment dose ranges. Obese patients: are at higher risk for thromboembolism however there is no consensus for dose adjustment; these patients should be observed carefully. Hyperkalaemia: Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia, particularly in patients such as those with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis, taking medicinal products known to increase potassium; plasma potassium should be monitored regularly especially in patients at risk. Traceability: In order to improve the LMWH traceability, it is recommended that health care professionals record the trade name and batch number of the administered product in the patient file. Sodium: For patients receiving doses >210mg/day, this medicine contains >24mg sodium, equivalent to 1.2% of the recommended maximum daily intake of sodium for an adult. Pregnancy and Lactation: Enoxaparin sodium should be used during pregnancy only if the physician has established a clear need. Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or excessive anticoagulation and should be warned of the haemorrhagic risk. If an epidural anaesthesia is planned, it is recommended to withdraw treatment before. Enoxaparin sodium can be used during breastfeeding. Interactions: Not

Recommended: Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including ketorolac. Other thrombolytics and anticoagulants. Caution: Platelet aggregation inhibitors including acetylsalicylic acid used at anti-aggregant dose (cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in acute coronary syndrome due to the risk of bleeding, Dextran 40. Systemic glucocorticoids. Medicinal products increasing potassium levels. Adverse Reactions: Very Common: Hepatic enzyme increases (mainly transaminases >3 times the upper limit of normality). Common: Haemorrhage, haemorrhagic anaemia, thrombocytopenia, thrombocytosis, allergic reaction, headache, urticaria, pruritus, erythema, injection site haematoma / pain / other reaction (such as oedema, haemorrhage, hypersensitivity, inflammation, mass, pain, or reaction). Uncommon: Hepatocellular liver injury, bullous dermatitis, local irritation, skin necrosis at injection site. Rare: Eosinophilia, cases of immuno-allergic thrombocytopenia with thrombosis (in some cases thrombosis was complicated by organ infarction or limb ischaemia), anaphylactic/anaphylactoid reactions including shock, spinal/neuraxial haematoma resulting in varying degrees of neurologic injuries including long-term or permanent paralysis, cholestatic liver injury, alopecia, cutaneous vasculitis, skin necrosis, injection site nodules, osteoporosis following therapy >3 months, hyperkalaemia. Please refer to the SPCs for full details.

Legal Category: POM. Marketing Authorisation (MA) Numbers: Clexane 2,000IU: PA540/97/4; Clexane 4,000IU: PA540/97/5; Clexane 6,000 IU: PA540/97/6; Clexane 8,000 IU: PA540/97/7; Clexane 10,000 IU: PA540/97/1; Clexane Forte 12,000 IU: PA540/97/8; Clexane Forte 15,000 IU: PA540/97/2. MA Holder and further information is available on request from: Sanofi Ireland Ltd., 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact IEmedinfo@sanofi.com Tel: 01 403 5600. Date of Preparation: May 2020.

Adverse events should be reported.

Reporting forms and information can be found at: www.hpra.ie; E-mail: medsafety@hpra.ie

Adverse events can also be reported to Sanofi Ireland Ltd. Tel: 01 403 5600. Alternatively, send via Email to IEPharmacovigilance@sanofi.com

Reference: 1. Data on File – Clexane IMS Data. MAT-IE-2000432 (v2.0).

Date of preparation: October 2020. Clexane (enoxaparin) SPC available at www.medicines.ie

® ®

treatment for AF has not been successful. The procedure restores the heart’s normal rhythm by electrically isolating the left atrium from the pulmonary veins where most abnormal electrical activity that promotes AF originates. The procedure destroys or ablates the diseased area of the heart and interrupts abnormal electrical circuits.

The principal reason to place a pacemaker in a patient with AF is to treat symptomatic bradycardia, especially due to sick sinus syndrome (tachycardiabradycardia syndrome). This tends to be mainly used in people aged 80 or over.

Differentiation between atrial flutter and AF

Atrial flutter is much less common than AF, but its causes and haemodynamic consequences are similar. About a third of people with atrial flutter also have AF. Both conditions carry increased risk of stroke. In AF, the atria beat irregularly. In atrial flutter, the atria beat regularly, but faster than usual and more often than the ventricles, and there may be four atrial beats to every one ventricular beat. During atrial flutter, unlike AF, electrical activity in the atria is coordinated. The atria do contract, but at a very rapid rate of 250 to 350 times per minute. This rate is too fast to allow every impulse to be conducted through the atrioventricular node to the ventricles. Because the AV node cannot usually conduct at this rate, typically half of the impulses get through (2:1 block), resulting in a regular ventricular rate of 150 beats/ minute. The diagnosis of atrial flutter is by electrocardiography. In typical flutter, ECG shows continuous and regular atrial activation with a saw tooth pattern, most obvious in leads II, III, and aVF.

Carotid sinus massage can increase AV block and better expose the typical flutter waves. A similar response may follow pharmacologic AV nodal blockade, example with adenosine, but such therapy does not terminate atrial flutter. Treatment of atrial flutter focuses on

ventricular rate control, rhythm control, and prevention of thromboembolism. Patients with chronic or recurrent atrial flutter require an oral anticoagulant. The choice among the therapies is based on the same considerations as for AF. Patients often require cardioversion or atrial flutter substrate ablation.

AF associated with one-in-three strokes in

Ireland

AF is the most common cardiac arrhythmia affecting at least 3 per cent of Irish adults over 60 and is associated with almost one in three strokes in Ireland. Globally the prevalence of AF is rising and approximately 600 men and 375 women per 100,000 population are affected. In the 2017 report Burden of Stroke in Europe, the Stroke Alliance for Europe signalled a possible 58 per cent increase in the absolute number of strokes in Ireland over the next decade. Much of this can be accounted for by increasing numbers of AF-related stroke as our population ages. The population aged 65 years and over in Ireland is increasing at the rate of 4 per cent annually. The CSO predicts that people aged over 65 will represent between 21.5-to-27.9 per cent of the Irish populationby 2046. As a result AF is a growing public health concern.

Screening for AF in general practice

Projections show that the number of people living with stroke as a chronic condition will rise from 3,718,785 in 2015 to 4,631,050 in 2035, representing an increase of 25 per cent or almost one million people across Europe. There are approximately 8,000 strokes in Ireland annually, a third of which are associated with AF.

In 2015, HIQA published a health technology assessment (HTA) of a national screening programme for AF in primary care. The HTA announced that a national screening programme for AF for over-65s in primary care would be cost-effective. HIQA’s Director of Health Technology Assessment Dr Máirín Ryan,

said: “Based on the best available evidence, annual opportunistic pulse palpation for those aged 65 and older is expected to lead to reductions in the incidence and severity of AF-related strokes assuming that those detected by screening have a comparable risk of stroke as those detected through routine care.”

Analysis estimated that screening would result in the detection of one additional AF case for every 22 people screened from age 65 onwards, and one stroke avoided for every 270 people screened over the same period. The total incremental cost to the HSE was estimated at €3.7 million over the first five years. This included the additional costs associated with screening, ECGs and AF drug therapy in diagnosed cases, as well as the cost savings resulting from a gradual decrease in stroke incidence over a period of five years.

Almost 11 per cent of Irish adults aged 65 years and over attending general practice have AF. The HSE (2015) study Atrial fibrillation screening in general practice also concluded that “opportunistic screening for an irregular pulse in general practice to assist in the detection of AF is both feasible and beneficial”. This multi-site prospective observational study found that approximately 8,415 new cases of AF could be identified by opportunistic screening in general practice each year. Each GP could expect to diagnose 17 new cases per 1,000 patients annually through opportunistic screening in practice. General practice is well placed to opportunistically screen older patients and is ideal in terms of the pathway for treatment for those identified. Opportunistic screening for an irregular pulse carried out by GPs and general practice nurses (GPNs) “has the potential to be an extremely important stroke prevention strategy, capable of saving society and the health service significant social and economic costs”. n

References on request

Volume 7 | Issue 4 | 2021 | Cardiology 20

Latest module

Cardiac amyloidosis- Overview, Diagnosis and Management

Learning objectives of this module:

l Understand the principal causes (AL amyloidosis and ATTR) and underlying pathophysiology of cardiac amyloidosis

l Identify patients to screen for cardiac amyloidosis and the subsequent diagnostic process

l Develop insight into the management of cardiac amyloidosis and its underlying causes

Successful completion of this module will earn you 2 CPD credits visit www.medilearning.ie/doctorcpd.

A B C

doctor

CPD.ie

Free CPD – now accessible on android, iPhone and tablet

Addressing the burden of coronary heart disease

AUTHOR: Dr Aftab Jan, Interventional Cardiologist, Beacon Hospital, Dublin

An estimated 17.7 million people die of cardiovascular diseases each year, representing 31 per cent of all global deaths. Coronary heart disease (CHD) mortality rates worldwide have declined over the past four decades, but CHD remains responsible for about one-third or more of all deaths in individuals over age 35 years. There is a high prevalence of coronary artery disease by middle age, more so in men compared to women, hence there is a rationale in timely detection. The first presentation with advanced obstructive coronary artery disease can be catastrophic, resulting in an acute myocardial infarction (MI) and sudden cardiac death with minimal or no previous symptoms. The detection at subclinical stages might permit the identification of subjects at increased risk of a cardiac event and appropriate therapy might improve the prognosis of those at high-risk.

The symptoms of coronary artery disease are an important predictor of outcome. However, a significant proportion of patients presenting with sudden cardiac death or MI can be asymptomatic and silent infarction is quite common in older patients with risk factors. Almost half of the patients presenting with sudden cardiac death may be previously asymptomatic. Among patients presenting with first acute MI, only half may have preceding angina. Silent MI represents up to one-third of MI with increasing prevalence over age 60 with cardiac risk factors.

Screening and risk estimation

The screening versus risk estimation for CHD carry certain similarities and differences; both are performed in asymptomatic individuals with an aim to improve outcome with intervention if needed. Screening identifies existing

disease whereas risk estimation predicts the likelihood of a future cardiovascular event. Adult patients with cardiovascular risk factors should undergo periodic cardiovascular risk assessment every threeto-five years.

The approach to screening and risk estimation (Figure 1) should include a detailed history, assessment of cardiac risks including family history, and the use of available various risk scoring systems, which can help categorise individuals into low (<10 per cent), intermediate (10-to20 per cent), and high-risk (>20 per cent) by estimating a 10-year cardiovascular risk. However, risk calculators are based on multivariable statistical models that perform moderately well at a population level. Caution needs to be exercised in asymptomatic individuals with risks, as risk calculators can place a high number

History should focus on detection of angina or anginal equivalent symptoms as well as an assessment of lifestyle factors

FAMILY HISTORY/ CARDIAC RISKS

RISK SCORE CALCULATION

Family history of premature atherosclerotic disease or sudden cardiac death.

RISK FACTORS: Diabetes, hypertension, hyperlipidaemia, smoking

FRS (1998) and ATP III hard CHD risk score (2001)

SCORE CVD: Death risk score (2003)

ACC/AHA pooled cohort hard CVD risk score (2013)

Volume 7 | Issue 4 | 2021 | Cardiology 22

HISTORY

FIGURE 1: Screening and risk assessment for coronary heart disease

Low yield for screening. Consider EST or CCS if clinical uncertainty

of asymptomatic individuals in low- or intermediate-risk categories where the risk of a first coronary event can be as high as 60-to-70 per cent. Also, they have limited value to discriminate individuals who will experience a coronary event.

The Framingham Risk Score (FRS) estimates risks of cardiovascular events in 10 years with a low-risk <10 per cent, intermediate-risk 10-to-20 per cent, and high-risk >20 per cent. It does not consider diabetes or family history of CHD. It does not incorporate diabetes or family history.

Guidelines

The current guidelines do not recommend routine screening in asymptomatic individuals. The United States Preventive Services Task Force (USPSTF)

CAREFUL HISTORY

(recommendations 2012) recommended against routine screening in adults at low risk for CHD events. American College of Cardiology/American Heart Association guidelines do not support routine exercise stress testing (EST) in asymptomatic adults, however, subgroups that may benefit from screening are:

 Asymptomatic patients with diabetes who plan to begin a vigorous exercise programme.

 Patients with multiple risk factors for CHD as a guide to risk reduction therapy.

 Men aged over 45 years and women aged over 55 years who are presently sedentary and plan to start a vigorous exercise programme.

 Patients who are involved in occupations linked to public safety like pilots, bus drivers, scuba divers, etc.

The American College of Sports Medicine supports EST in men/women >40/50 years of age with multiple risk factors starting a vigorous exercise programme.

Screening approach

The screening of asymptomatic patients for CHD starts with a good history, assessment of risks and use of various risk calculators which stratify the patients into low-, intermediate- and high-risk categories (Figure 2).

Screening tools for CHD include a lipid profile, high sensitivity C reactive protein (Hs-CRP), resting ECG and ambulatory ECG, which can identify silent ischaemia and arrhythmias. Further tests include EST, myocardial perfusion imaging (MPI) and stress echocardiography, which are

23 Cardiology | Volume 7 | Issue 4 | 2021

FIGURE 2: Proposed screening for coronary heart disease in asymptomatic patients

*EST if uncertain symptoms and functional status. Coronary angiography may be considered in patients where other non-invasive tests remain non diagnostic Abbreviations: EST (exercise stress test), CCS (coronary calcium score), GDMT (guideline-directed medical therapy) Consider CCS. If high-risk after CCS maximise GDMT ± EST* Maximise GDMT± EST*

RISK FACTORS/FAMILY HISTORY/ATYPICAL SYMPTOMS/FUNCTIONAL STATUS

LOW-RISK INTERMEDIATE-RISK HIGH-RISK

RISK CALCULATOR

alternative tests in individuals unable to exercise. Coronary calcium score (CCS) and CT angiography can directly identify the presence of atherosclerotic coronary disease but CT providing functional information is not widely available yet. CCS provides additional prognostic information to most risk scores (Figure 3).

Cardiac MRI and perfusion scans can also be employed in certain patients for detection of cardiovascular disease. On occasions, coronary angiography can be considered as a first-line test in high-risk patients where other non-invasive tests remain non-diagnostic.

Limitations

The limitations of the non-invasive tests should be kept in mind. EST in an asymptomatic patient can indirectly identify the presence or absence of underlying obstructive CHD by assessing myocardial ischaemia, but there are false positives and false negative results; the mean sensitivity of the test is 68 per cent with a mean specificity 77 per cent. The resting ECG in approximately 30-to-50 per cent of individuals with a normal coronary angiogram have ECG abnormalities. Approximately 30 per cent of individuals with angiographicallyproven CHD have a normal resting ECG. Most coronary events occur in individuals without resting ECG abnormalities.

Management

The management of high-risk individuals centres on lifestyle modification and guideline-directed medical therapy (GDMT) known to reduce coronary events and improve survival. The approach includes smoking cessation, diet and exercise, and modification of risk factors. As for GDMT, the addition of moderate- or high-intensity statins based on baseline LDL, presence of diabetes and estimated 10-year cardiovascular disease risk along with the treatment of blood pressure and HbA1C to goal, if applicable. Beta blockers and calcium channel blockers have been shown to reduce silent ischaemia. Other agents include aspirin, statins, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Coronary revascularisation is appropriate for asymptomatic patients only if very high-risk anatomy or high-risk noninvasive testing despite medical therapy. Residual ischaemia at six-to-18 months is a significant predictor of future death or MI regardless of the strategy.

In summary

In summary, there is no role for routine screening of asymptomatic low-risk

individuals but for intermediate- and high-risk categories of patients the detection of CHD at subclinical stages may identify individuals at high-risk of a coronary event and appropriate therapy might improve prognosis. The primary purpose of screening for CHD is to identify patients whose prognosis could be improved with an intervention (ie, aggressive medical therapy or coronary intervention). A good history is the cornerstone of diagnosing CHD; use other adjuncts to reach a diagnosis and appropriateness for screening. Screening for CHD identifies existing disease while risk estimation for CHD does not directly identify existing disease, but rather the likelihood of any future event. Asymptomatic patients at low-risk: There is no role in performing screening electrocardiograms, stress testing, CCS, or coronary angiography. Candidates for CHD screening are ‘special populations’ in which a CHD event may pose unique or additional risks beyond those in the average population. Coronary intervention in stable patients does not improve outcomes; medical therapy does. n

References on request

Volume 7 | Issue 4 | 2021 | Cardiology 24

Population/N 10-year low-risk threshold CCS threshold Impact on risk stratification MESA 6814 <7.5% 300 Neg. CCS: 10y event rate = 3% Pos. CCS: 10y event rate = 13% Framingham* 3529 10% 100 If intermediate risk by FRS: Neg. CCS = 25% >low-risk Pos. CCS = 39% >high-risk South Bay 1461 10% 300 Pos. CCS predicted individual risk if: FRS>10% (p>0.05 if ≤10%) FRS 10-15%: HR 17.6 (3.7-83.0) FRS 16-20%: HR 8.9 (1.9-41.8)

CLASSIFICATION OF INDIVIDUAL RISKS BY CORONARY CALCIUM SCORE (CCS) FIGURE 3: CCS prognostic information * Offspring and 3rDgen. cohort Ao (Aorta), LA (Left Atrium)

Thanks to you...

6 Available Formulations

prevention

The 1st polypill licensed for secondary prevention of cardiovascular events in Ireland

Reduce pill burden by 730 pills per year*

Capsules shown are not actual size. Capsules are Size 0. Please refer to SmPC before prescribing.

*The calculation of a reduction of 730 pills per year is based on a patient taking the three individual components of Trinomia (aspirin, atorvastatin, ramipril) on a daily basis for 365 days compared to a patient taking a Trinomia capsule once daily for 365 days.

Trinomia 100 mg/20 mg/10 mg, 100 mg/20 mg/5 mg, 100 mg/20 mg/2.5 mg hard capsules (acetylsalicylic acid, atorvastatin (as atorvastatin calcium trihydrate) and ramipril) and Trinomia 100 mg/40 mg/10 mg, 100 mg/40 mg/5 mg, 100 mg/40 mg/2.5 mg hard capsules (acetylsalicylic acid, atorvastatin (as atorvastatin calcium trihydrate) and ramipril) Abbreviated Prescribing Information Please consult the Summary of Product Characteristics (SmPC) for full prescribing information. Presentation: Hard capsules containing: two 50 mg acetylsalicylic film-coated tablets, two 10 mg atorvastatin film-coated tablets and one 10 mg ramipril film-coated tablet; or two 50 mg acetylsalicylic filmcoated tablet, two 10 mg atorvastatin film-coated tablets and one 5 mg ramipril film-coated tablet; or two 50 mg acetylsalicylic film-coated tablet, two 10 mg atorvastatin film-coated tablets and one 2.5 mg ramipril film-coated tablet; or two 50 mg acetylsalicylic film-coated tablets, two 20 mg atorvastatin film-coated tablets and one 10 mg ramipril film-coated tablet; or two 50 mg acetylsalicylic film-coated tablet, two 20 mg atorvastatin film-coated tablets and one 5 mg ramipril film-coated tablet; or two 50 mg acetylsalicylic film-coated tablet, two 20 mg atorvastatin film-coated tablets and one 2.5 mg ramipril film-coated tablet. Uses: Secondary prevention of cardiovascular accidents as substitution therapy in adult patients adequately controlled with the monocomponents given concomitantly at equivalent therapeutic doses Dosage: Oral administration. 1 capsule per day, preferably after a meal. Swallow with liquid. Do not chew or crush. Avoid grapefruit juice. Patients currently controlled with equivalent therapeutic doses of acetylsalicylic acid, atorvastatin and ramipril can be directly switched. Treatment initiation should take place under medical supervision. Cardiovascular prevention, target maintenance dose of Ramipril is 10 mg once daily. Daily dose in renal impairment based on creatinine clearance - ≥ 60 ml/min, maximum daily dose is 10 mg ramipril; 30-60 ml/min, maximum daily dose is 5 mg ramipril. Contraindicated in hemodialysis and/or with severe renal impairment (creatinine clearance <30 ml/min). Administer with caution with hepatic impairment. Perform liver function tests before initiation of treatment and periodically thereafter. Maximum daily dose is 2.5 mg ramipril and initiate treatment under close medical supervision. Contraindicated in severe or active hepatic impairment. Start treatment in very old and frail patients with caution. In patients taking elbasvir/grazoprevir concomitantly with atorvastatin, the dose of atorvastatin should not exceed 20 mg/day. Contraindications: Hypersensitivity to any component, to other salicylates, to NSAIDs, to any other ACE inhibitors, tartrazine, soya or peanut. History of previous asthma attacks or other allergic reactions to salicylic acid or other NSAIDs. Active, or history of recurrent peptic ulcer and/or gastric/intestinal haemorrhage, other kinds of bleeding. Haemophilia and other bleeding disorders. Severe kidney and liver impairment. Hemodialysis. Severe heart failure. Concomitant treatment with methotrexate at a dosage of 15 mg or more per week. Concomitant use with aliskiren-containing products with diabetes mellitus or renal impairment. Nasal polyps associated with ashma induced or exacerbated by acetylsalicylic acid. Active liver disease or unexplained persistent elevations of serum transaminases. Pregnancy, lactation and in women of child-bearing potential not using appropriate contraceptive measures. Concomitant treatment with tipranavir, ritonavir, ciclosporin, glecaprevir/pibrentasvir,sacubitril/valsartan therapy. Trinomia must not be initiated earlier than 36 hours after the last dose of sacubitril/valsartan. History of angioedema. Extracorporeal treatments leading to contact of blood with negatively charged surfaces. Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney. Hypotensive or haemodynamically unstable states. Children and adolescents below 18 years of age. Warnings and Precautions: Only for use as a substitution therapy in patients adequately controlled with the monocomponents given concomitantly at equivalent therapeutic doses. Special populations requiring particularly careful medical supervision: Hypersensitivity to other analgesics/antiinflammatory/antipyretic/antirheumatics or other allergens. Other known allergies, bronchial asthma, hay fever, swollen nasal mucous membranes and other chronic respiratory diseases. History of gastric or enteric ulcers, or of gastrointestinal bleeding. Reduced liver and/or renal function. Particular risk of hypotension: strongly activated renin-angiotensin-aldosterone system, transient or persistent heart failure post MI, risk of cardiac or cerebral ischemia, in case of acute hypotension medical supervision including blood pressure monitoring is necessary. Deterioration of cardiovascular circulation. Glucose 6 phosphate dehydrogenase deficiency. Risk of elevated levels of uric acid. Consumption of substantial quantities of alcohol and/or have a history of liver disease. Diagnosed pregnancy, stop treatment immediately, and, if appropriate, start alternative therapy. ACE inhibitors cause higher rate of angioedema in black patients than in non-black patients. The blood pressure lowering effect of ACE inhibitors is somewhat less in black patients than non-black patients. Monitoring during treatment is required for: Concomitant treatment with NSAIDs, corticosteroids, SSRIs, antiplatelet drugs, anticoagulants, ibuprofen. Signs or symptoms suggestive of liver injury. Stop treatment temporarily prior to elective major surgery and when any major medical or surgical condition occurs. Particularly careful monitoring is required in patients with renal impairment, risk of impairment of renal function, particularly with congestive heart failure or after a renal transplant. Serum potassium: ACE inhibitors can cause hyperkalemia in patients with impaired renal function and/or in patients taking potassium supplements (including salt substitutes), potassium-sparing diuretics, trimethoprim or co-trimoxazole and especially aldosterone antagonists or angiotensin-receptor blockers, hyperkalemia can occur. Potassium-sparing diuretics and angiotensin-receptor blockers should be used with caution in patients receiving ACE inhibitors, and serum potassium and renal function should be monitored. Other situations that may increase the risk of hyperkalaemia are: age >70 years, uncontrolled diabetes mellitus, dehydration, acute cardiac decompensation or metabolic acidosis.Specific side-effects: Perform liver function tests before use and monitor periodically and with liver injury or increased transaminase levels. Use with caution with substantial alcohol use or history of liver disease. Potential risk of hemorrhagic stroke. May affect the skeletal muscle and cause myalgia, myositis, and myopathy that may progress to rhabdomyolysis, ask patients to promptly report skeletal muscle effects (muscle pains, cramps or weakness) especially if accompanied by malasie or fever and measure CK levels, stop treatment if significantly elevated or if severe muscular symptoms occur. Prescribe with caution in patients with pre-disposing factors for rhabdomyolysis. Benefit/risk of treatment should be considered and clinical monitoring recommended. Do not measure CK following strenuous exercise or in presence of plausible alternative cause of CK increase. If CK levels significantly elevated at baseline, re-measure levels 5 to 7 days later to confirm the results. Risk of rhabdomyolsis with use of potent CYP3A4 inhibitors, transport proteins or HIV protease inhibitors. Consider alternative treatments if risk of myopathy. Consider lower starting or maximum dose and appropriate clinical monitoring with potent CYP3A4 inhibitors and medicinal products that increase the plasma concentration of atorvastatin respectively. The risk of myopathy may also be increased with the concomitant use of gemfibrozil and other fibric acid derivates, antivirals for the treatment of hepatitis C (HCV) (boceprevir, telaprevir, elvasvir/grazoprevir), erythromycin, niacin or ezetimibe. Do not co-administer with systemic fusidic acid or within 7 days of stopping fusidic acid. Where use of systemic fusidic acid considered essential, discontinue statin treatment during fusidic acid treatment. Reports of rhabdomyolysis in patients receiving fusidic acid and statins in combination. Where prolonged systemic fusidic acid needed, consider need for co-administration of Trinomia and fusidic acid on case by case basis with close medical supervision. Discontinue statin treatment if interstitial lung disease occurs. Monitor patients at risk of diabetes mellitus. Discontinue treatment if angioedema occurs and initiate emergency treatment promptly. Concomitant use of ACE inhibitors with sacubitril/valsartan is contraindicated. due to the increased risk of angioedema. Treatment with sacubitril/valsartan must not be initiated earlier than 36 hours after the last dose of Trimomia. Caution should be used when starting racecadotril, mTOR inhibitors and vildagliptin in a patient already taking an ACE inhibitor as there is an increased risk of angioedema. Concomitant use of ACE-inhibitors and angiotensin II receptor blockers or aliskiren is not recommended and should not be used in patients with diabetic nephropathy. Anaphylactic reactions during desensitization, consider temporary discontinuation of Trinomia during desensitization. Monitor white blood cells for neutropenia/agranulocytosis and more regularly in the initial phase of treatment, impaired renal function, concomitant collagen disease and other medicines that can change the blood picture. Cough. Contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Interactions: Acetylsalicylic acid: other platelet aggregation inhibitors, other NSAIDs, and antirheumatics, systemic glucocorticoids, diuretics, alcohol, SSRIs, uricosuric agents, metamizole, anticoagulant and thrombolytic therapy, digoxin, antidiabetic agents including insulin, methotrexate, valproic acid, antacids, ACE inhibitors, ciclosporin, vancomycin, interferon , lithium, barbiturates, zidovudine, phenytoin, laboratory tests. Atorvastatin: CYP3A4 inhibitors, CYP3A4 inducers, transport protein inhibitors, gemfibrozil/fibric acid derivatives, ezetimibe, colestipol, fusidic acid, colchicine, digoxin, oral contraceptives, warfarin. Ramipril: potassium salts, heparin, potassium-retaining diuretics and other plasma potassium increasing active substances, antihypertensive agents and other substances that may decrease blood pressure, vasopressor sympathomimetics and other substances, allopurinol, immunosuppressants, corticosteroids, procainamide, cytostatics and other substances that may change the blood cell count, lithium salts, antidiabetic agents including insulin. Monitor as appropriate. Consider lower maximum dose of atorvastatin with potent CYP3A4 inhibitors. Pregnancy and Lactation: Contraindicated in pregnancy and breast-feeding. Women of child-bearing potential should use effective contraception during treatment. Side Effects: Ramipril: Common (≥1/100, <1/10): dyspepsia, nausea, diarrhoea, vomiting, digestive disturbances, abdominal discomfort, gastrointestinal inflammation, non-productive tickling cough, bronchitis, sinusitis, dyspnoea, headache, dizziness, rash in particular maculo-papular, blood potassium increased, myalgia, muscle spasms, chest pain, fatigue, hypotension, orthostatic blood pressure decreased, syncope. Atorvastatin: Common: dyspepsia, nausea, diarrhoea, constipation, flatulence, pharyngolaryngeal pain, epistaxis, nasopharyngitis, headache, allergic reactions, hyperglycaemia, myalgia, muscle spasms, pain in extremity, joint swelling, back pain, arthralgia, liver function test abnormal, blood creatine kinase increased. ASA: Very Common (≥ 1/10): Gastrointestinal complaints such as heartburn, nausea, vomiting, stomach ache and diarrhea, minor blood loss from the gastrointestinal tract (micro-bleeding). Common: Paroxysmal bronchospasm, serious dyspnoea, rhinitis, nasal congestion. For less frequent side effects see SmPC. Pack Sizes: Blister containing 28 hard capsules. Legal Category: POM. Product Authorisation Numbers: PA 1744/002/001-006 Product Authorisation

aspirin • atorvastatin

Aspirin Atorvastatin Ramipril 100mg 20mg 2.5mg 100mg 20mg 5mg 100mg 20mg 10mg 100mg 40mg 2.5mg 100mg 40mg 5mg 100mg 40mg 10mg

Holder: Ferrer Internacional, S.A., Gran Vía Carlos III, 94, 08028 Barcelona, Spain. Marketed by: A. Menarini Pharmaceuticals Ireland Ltd. Further information is available on request from A. Menarini Pharmaceuticals Ireland Ltd, 2nd Floor, Castlecourt, Monkstown Farm, Monkstown, Glenageary, Co. Dublin A96 T924 or may be found in the SmPC. Date of Preparation: March 2020 Date of item: July 2020. IR-TRI-05-2020 References: 1. Trinomia 100mg / 40mg / 10mg, 100mg / 40mg / 5mg, 100mg / 40mg / 2.5mg SmPC March 2020 2. Trinomia 100mg / 20mg / 10mg, 100mg / 20mg / 5mg, 100mg / 20mg / 2.5mg SmPC March 2020

Aspirin Atorvastatin Ramipril

ESC: Cardiovascular disease in women

Chest pain is misdiagnosed in women more frequently than in men, according to research presented at the European Society of Cardiology (ESC) Acute CardioVascular Care 2021 congress, held in March. The study also found that women with chest pain were more likely than men to wait over 12 hours before seeking medical help.

“Our findings suggest a gender gap in the first evaluation of chest pain, with the likelihood of heart attack being underestimated in women,” said study author Dr Gemma Martinez-Nadal, Spain. “The low suspicion of heart attack occurs in both women themselves and in physicians, leading to higher risks of late diagnosis and misdiagnosis.”

This study examined gender differences in the presentation, diagnosis, and management of patients admitted with chest pain to the chest pain unit of an emergency department between 2008 and 2019. Information was collected on risk factors for a heart attack including high blood pressure and obesity. The researchers recorded the physician’s initial diagnosis after the first evaluation of each patient, which is based on clinical history, physical examination, and an electrocardiogram (ECG) and occurs before other examinations like blood tests.

A total of 41,828 patients with chest pain were included, of which 42 per cent were women (median age 65). The median age in men was 59 years. Women were significantly more likely (41 per cent versus 37 of men) to present late to the hospital (defined as waiting 12 hours or longer after symptom onset).

“This is worrying since chest pain is the main symptom of reduced blood flow to the heart (ischaemia) because an artery has narrowed,” said Dr Martinez-Nadal. “It can lead to a myocardial infarction, which needs rapid treatment.”

In the physician’s initial diagnosis, acute coronary syndrome (ACS) was more likely to be considered the cause of chest pain in men compared to women. Specifically, in 93 per cent of patients, the ECG did not provide a definitive diagnosis. In those patients, the doctor noted a probable ACS in 42 per cent of cases – when analysed according to gender, probable ACS was noted in 39 per cent of women and 44.5 per cent of men (p<0.001). The significantly lower suspicion of ACS in females was maintained regardless of the number of risk factors or the presence of typical chest pain.

Dr Martinez-Nadal said: “In the doctor’s first impression, women were more likely than men to be suspected of a non-ischaemic problem. Risk factors like hypertension and smoking should instil a higher suspicion of possible ischaemia in patients with chest pain. But we observed that women with risk factors were still less likely than men to be classified as ‘probable ischaemia’.”

In women, 5 per cent of ACS were initially misdiagnosed, whereas in men, 3 per cent of ACS were initially misdiagnosed (p<0.001). After multivariate analysis, female gender was an independent risk factor for an initial impression of non-ACS.

Hypertension symptoms in women often mistaken for menopause

Cardiologists, gynaecologists and endocrinologists have laid out recommendations on how to help middleaged women prevent later heart problems in a new ESC consensus document published recently in the European Heart Journal

The document provides guidance on how to manage heart health during menopause, after pregnancy complications, and during other conditions such as breast cancer and polycystic ovarian syndrome (PCOS). The important role of a healthy lifestyle and diet is recognised – eg, for optimal

management of menopausal health and in women with PCOS who have elevated risks of high blood pressure during pregnancy and type 2 diabetes.

“Physicians should intensify the detection of hypertension in middle-aged women,” states the document. Up to 50 per cent of women develop high blood pressure before the age of 60 but the symptoms – for example, hot flushes and palpitations – are often attributed to menopause.

“High blood pressure is called hypertension in men, but in women it is often mistakenly labelled as ‘stress’ or ‘menopausal symptoms’,” said first author Prof Angela Maas. “We know that blood pressure is treated less well in women compared to men, putting them at risk for atrial fibrillation, heart failure and stroke – which could have been avoided.

“There are several phases of life when we can identify subgroups of high-risk women,” said Prof Maas. “High blood pressure during pregnancy is a warning sign that hypertension may develop when a woman enters menopause and it is associated with dementia many decades later. If blood pressure is not addressed when women are in their 40s or 50s, they will have problems in their 70s when hypertension is more difficult to treat.”

While menopausal hormone therapy is indicated to alleviate symptoms, such as night sweats and hot flushes in women over 45, the authors recommend assessment of cardiovascular risk factors before initiation. Therapy is not recommended in women at high cardiovascular risk or after a stroke, heart attack, or blood clot.

The document also provides advice for transgender women. “These women need hormone therapy for the rest of their lives and the risk of blood clots increases over time,” said Prof Maas. n

AUTHOR: Priscilla Lynch

Raising awareness of cardiovascular disease in women

AUTHOR: Priscilla Lynch

Cardiovascular disease is often perceived as a man’s disease, but it impacts men and women equally; almost 5,000 women in Ireland die from heart disease and stroke annually, making it the leading cause of death for women.

In fact, women are almost seven times more likely to die from cardiovascular disease than breast cancer, yet the traditional image of a heart attack is a man clutching their chest. Moreover, the literature shows that women can experience delays in being diagnosed correctly, being less likely to get the required diagnostics or be treated as quickly and aggressively as their male counterparts.

The warning signs of a myocardial infarction (MI) can be more subtle in women than men, noted Dr Róisín Colleran, Consultant Interventional Cardiologist for the Mater Private Network, who has helped raise public awareness of this issue, encouraging women in Ireland to “listen to their heart” and to look out for the early signs and symptoms of heart disease.

The most common presenting symptom of angina or MI in both women and men is central chest discomfort, often described as a pressure, intense heaviness, tightness or squeezing. However, in women, symptoms can be more subtle or atypical than in men, making the diagnosis more likely to be delayed or missed, sometimes being attributed to anxiety, menopause, stress or over-exertion, she told Update

Women are more likely than men to experience symptoms such as stomach, back, shoulder or throat pain, indigestion, nausea or vomiting, shortness of breath, or fatigue rather than chest pain. “When people don’t have those typical symptoms

there isn’t the same index of suspicion. So studies have shown that heart attack, coronary heart disease, or angina may be underdiagnosed or at least be delayed diagnosed in women because of this tendency towards atypical presentation.”

In addition, “women tend to develop heart disease about 10 years later than men, because we are generally protected by oestrogen before menopause. So with younger women your index of suspicion would be less, but over the lifetime, the risk of death from cardiovascular disease in men and women is in fact equal. Women live longer and have more time to develop it after menopause.”

Prevention

Up to 90 per cent of cardiovascular disease is preventable. Given the increasing rise of cardiovascular risk factors such as obesity, diabetes and the metabolic syndrome in the population, prevention through addressing lifestyle issues such as quitting smoking, healthy diet, and regular exercise is key, said Dr Colleran. “While we can’t change some risk factors, such as age and family history of early heart disease, there

is something we can do at every stage of life to reduce our risk of heart disease and stroke. Smoking is such a preventable risk factor; it really increases the risk of heart disease and stroke.”

People should get to know their heart health numbers and risk factors – blood pressure, cholesterol, blood sugar levels –and work with their doctor to make sure these are at target, “and be proactive and take responsibility for it rather than it just being a passive process.”

“In addition, screening for conditions such as diabetes and high blood pressure is also important. We often see dramatic drops in blood pressure in those who lose a few stone, without medication, so it really is a big risk factor across the board.”

However, Covid-19 is having an ongoing negative impact, in both slower presentation of patients with MI symptoms, leading to poorer outcomes, and less chances for opportunistic diagnosis of issues like high blood pressure given the huge reduction in physical GP and outpatient appointments, pointed out Dr Colleran.

Female-specific risk factors

A history of pre-eclampsia, high blood pressure during pregnancy, gestational diabetes, and PCOS are risk factors for heart disease specific to women, noted Dr Colleran. If a woman has had any of these conditions, they should take extra care to try to control other risk factors for cardiovascular disease.

Women who go through premature menopause, either naturally or because they have had their ovaries removed, are twice as likely to develop heart disease as women of the same age who have not yet gone through menopause, she added.

27 Cardiology | Volume 7 | Issue 4 | 2021

Dr Róisín Colleran

Positively impacting the burden of heart failure through partnership

AUTHOR: Mairead Lehane, Advanced Nurse Practitioner: Heart Failure, Mallow General Hospital

Responding to the complex care needs of patients with chronic diseases is one of the many challenges facing the Irish health service. Collectively, chronic diseases (cardiovascular, cancer, respiratory, diabetes, and other diseases) represent two-thirds of European mortality and morbidity, a rate that escalates with time. The growing prevalence of heart failure (HF), affecting 64.3 million adults globally, is influenced by an ageing population, improvements in cardiovascular disease (CVD) management and increasing CVD survivorship. HF management is punctuated by decompensation, frequent hospitalisation and poor quality-of-life. High rates of hospitalisation occur within the first 30 days of discharge, frequently of non-cardiovascular causes. Following diagnosis, half of patients with HF can be readmitted at least once and 80 per cent will be readmitted within five years. Mortality is substantial (20 per cent) in the year following a HF hospitalisation, and 50 per cent die within five years. One-in-five Irish men and women will develop HF in their lifetime; the prevalence will rise to 10 per cent in those aged 70 years or more and is expected to rise by 150 per cent in Ireland in the next 30 years. HF is a significant cost to the health service; estimated at €660 million per annum in Ireland or 1.2 per cent of the total healthcare budget.

A dose-dependent relationship exists between evidence-based HF medications and HF re-admission and mortality. Higher doses are associated with higher event-free survival. Despite proven efficacy, HF therapy is underprescribed and under-dosed. A European study (11 countries) estimated that only 22 per cent of patients achieved recommended target doses. The flexibility of nurse-led titration leads to 53-to-49 per cent higher doses attained in nurse-led clinics than usual care. A Cochrane Review (n=1684) of nurse-

led titration of ACE/ARB and beta-blockers for people with HF found all-cause hospital admission were reduced by a fifth, HF-related hospital admissions were reduced by half, and a third of patients were less likely to die compared to usual care. In an age of clinical and fiscal turmoil, advanced nurse practitioner (ANP) caseload management has favourable outcomes in terms of rehospitalisation and waiting lists. The absence of personalised HF treatment plans can result in sub-optimal or overly aggressive treatment strategies, providing ANPs an opportunity to act as a dovetail between secondary and

primary care for seamless care planning and delivery. Covid-19 has amplified the need for this co-operation and partnership to meet patient care needs and escalates the need to embrace the tenets of Sláintecare policy. Practice nurses and public health nurses have an under-acknowledged expertise in managing multi-morbidity, which needs to be harnessed more fully and merged with HF expertise.

Definition and classification

The European Society of Cardiology (ESC 2016) defines HF as a clinical syndrome

(Valiant Trial)

Losartan 12.5-100mg od Max dose 150mg (ELITE-II and OPTIMAAL Trials)

Angiotensin receptor neprilysin inhibitor – ARNI Sacubitril/valsartan (Entresto) 24/26mg bd - 49/51bd97/103mg bd (PARADIGM-HF Trial, 2014)

Beta-blockers Bisoprolol 1.25- 10mg od (CIBIS II Study)

Carvediolol 6.25-12.5-25mg 50mg if weight >85kg (COPERNICUS Study)

Nebivolol 1.25mg -10mg od (SENIORS Study)

If channel inhibitor

Ivabradine 5- 7.5mg bd (Shift Trial, 2010)

MRA Spironolactone 25-50mg od (RALES Trial,1999)

Eplerenone 25-50mg od (EMPHASIS-HF, 2011)

Cardiac glycosides Digoxin 62.5-125mcg od (DIG Trial, 1997)

Volume 7 | Issue 4 | 2021 | Cardiology 28

CLASS MEDICATION USUAL DAILY DOSE TRIAL/EVIDENCE Loop diuretic Furosemide 40-240mg Bumetanide 1-5mg Thiazide diuretics Bendrofluazide (Centyl) 2.5-10mg Metolazone Refer to cardiology ACE inhibitors Ramipril 2.5-10mg od (AIRE Trial) Enalapril 2.5-20 bd (CONSENSUS Trial) Perindopril 2.5-10mg (EUROPA Trial) Lisinopril 2.5-35mg No substantive RCT Angiotensin receptor Candesartan 4-8-16-32mg od (CHARM Trial) Blocker Valsartan 40-80-120-160mg bd

TABLE 1: Drugs used to treat heart failure

characterised by typical symptoms (eg, breathlessness, ankle swelling, and fatigue) that may be accompanied by signs (eg, elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.

HF is classified by either symptom severity or functional classes (New York Heart Association; NYHA) in Europe or by disease progression (Stages A-D) in the US.

Guidelines classify HF into three groups according to left ventricular ejection fraction (LVEF); HF with reduced ejection fraction with EF <40 per cent (HFrEF), HF with mid range ejection fraction with EF 40-to-49 per cent (HFmrEF), and HF with preserved ejection fraction (HFpEF) with EF >50 per cent.

The HF patient journey has three phases: Acute, chronic stable, and end of life. Newonset HF may occur acutely as pulmonary oedema or more gradually as a deterioration in symptoms. Patients unchanged for a month are considered stable, and chronic stable patients with deteriorating symptoms are termed ‘decompensated’ and may require hospital avoidance measures such as diuretic titration or hospitalisation.

Multimorbidity and risk factors

HF is disproportionately prevalent in the elderly with over half of HF hospitalisation in those aged over 75 years, highlighting the need to integrate care of the elderly skills into HF management. In primary care, HF will go unrecognised in one-in-six patients (ESC 2016). Multimorbidity in HF is common and growing; in 2002 68 per cent of HF patients had more than three co-morbidities rising to 87 per cent in 2014. Co-morbidity adversely affects symptom severity, quality-of-life and prognosis. Additional comorbidities such as chronic kidney disease, chronic obstructive airways disease, sleep apnoea, and geriatric syndromes such as frailty, falls, confusion, and incontinence, influence patient outcome.

Predisposing risk factors to HF include coronary heart disease, hypertension, smoking, diabetes, and obesity. Ironically, improved survival post-MI has resulted in ischaemic heart disease becoming a major contributor to HF. Hypertensive patients have double the risk of normotensive patients of developing HF with early hypertension trials reducing the risk of HF by 87 per cent. Diabetes has a bidirectional relationship with HF and is prevalent in 40-to-45 per cent of HF patients, but often goes unrecognised as a sedentary lifestyle masks the symptoms. Much overlap in terms of clinical features and pathophysiology exists between HF and obesity; both conditions are characterised by a reduction in exercise capacity, retention of salt and water, plasma volume expansion and enlargement of the ventricles. Obesity is an independent risk factor for HF, as it suppresses natriuretic peptides making diagnosis more challenging but once HF is diagnosed obesity is associated with lower mortality, which is known as the obesity paradox. Risk of HF is independently increased by 62 per cent in patients with low socioeconomic status, with deprivation unfavorably influencing behaviours, such as diet, exercise, smoking, and medication concordance. The opportunities for aggressive risk factor management is boundless.

Signs and symptoms

Clinical assessment is fundamental to nursing practice, firstly to assist in diagnosis and secondly, to monitor progress in known HF patients. Symptoms and signs of HF include dyspnoea, fatigue, limited exercise tolerance, fluid retention, which may lead to pulmonary congestion, and peripheral oedema. Generally signs and symptoms are as a consequence of reduced cardiac output and an accumulation of excess fluid. Fatigue is ubiquitous to HF, reported as occurring on light (43 per cent) or moderate (43 per cent) exertion with only 5 per cent reporting no fatigue. Fatigue is a subjective, distressing and common symptom in HF, negatively impacting everyday activities, quality-of-life and prognosis. Depression (80 per cent increased likelihood), syncope (61 per cent), volume depletion (56 per cent), female gender (37 per cent), dyspnoea (33 per cent), anaemia (32 per

CARDIAC CAUSES NON-CARDIAC CAUSES

HF including RV syndromes

Acute coronary syndrome

Heart muscle disease, LVH

Hypertrophic/restrictive cardiomyopathy

Valvular heart disease

Congenital heart disease

Pericardial disease

Atrial fibrillation

Cardioversion, ICD shock

Myocarditis

Cardiac surgery

Toxic-metabolic insults, eg, chemotherapy

Advancing age

Anaemia

Renal failure

Liver dysfunction

Thyrotoxicosis, DKA

Ischaemic stroke

COPD

Obstructive sleep

apnoea

Severe pneumonia

Critical illness

Sepsis

Severe burns

cent), palpitations (32 per cent), and chest pain (31 per cent), were some of the strongest predictors of fatigue.

HF patients consider dyspnoea as the most debilitating symptom. Orthopnoea can be quantified by the number of pillows the patient uses and is a symptom specific to HF. Paroxysmal nocturnal dyspnoea (PND) is a sensation of sudden breathlessness at night typically two hours after going to bed, relieved by sitting up and classically described as gasping for breath by an open window. It is an important red flag for decompensation, often heralding the onset of pulmonary oedema by one or two days. The subjective nature of dyspnoea makes it challenging to assess as much overlap can occur between HF, lung disease, deconditioning, and obesity. Furthermore, due to impaired awareness and altered sensory perception in older adults, early recognition of dyspnoea may be assigned to a normal ageing process. Cognitive impairment is also a barrier to symptom recognition and responsiveness.

Dyspnoea in HF decompensation is related to volume overload or fluid retention as seen by a rapid increase in body weight. A 2kg weight

29 Cardiology | Volume 7 | Issue 4 | 2021

TABLE 2: Potential causes of elevated natriuretic peptide levels (ESC HF guidelines 2016)

increase over two-to-three days has been shown to be related to clinical deterioration, emphasising the need for patient education and self-care advice. Peripheral oedema is commonly related to an elevated right atrial pressure secondary to left ventricular failure or advanced lung disease and may also manifest as sacral oedema in dependent areas due to prolonged bed rest. Oedema as a clinical sign is variable and influenced by nutritional status, dietary salt intake and body position. Backward congestion of right HF causes ascites and hepatomegaly.

Diagnosis is based on a combination of history, physical examination, ECG, naturetic peptides and the gold standard echocardiography. B-type natriuretic peptide (BNP) is a neuro-hormone released into the bloodstream in response to ventricular wall stress. Echocardiography determines underlying causes and directs effective management strategies.

Guideline-directed medical therapy (GDMT)

HF management can be divided into three main pillars; pharmacology, cardiac devices, and non-pharmacology/self-care skills. The fundamental goal of treatment in HF is to reduce mortality and morbidity, reduce hospital admission and improve qualityof-life. Prior to 1990 and the era of GDMT, the mortality rate was 60-to-70 per cent within five years of diagnosis, underscoring the importance of up-titration of GDMT to maximum tolerated doses. Common wisdom advocates a ‘start low and go slow’ approach. Furthermore, an underlying philosophy of shared decision-making should prevail between patients, carers, and health professionals.

The 2016 ESC HF guidelines advocate decongestion of fluid overload using diuretics, individualised to the patient’s clinical status with euvolaemia as the overall goal of care. Diuretics improve symptoms and reduce the risk of hospitalisation, but do not reduce mortality. An over-activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system is a principle mechanism in worsening HF. The

mainstay of treatment is neurohormonal blockade, used to improve symptoms, for hospital avoidance and to reduce mortality. This classification includes angiotensinconverting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), betablockers (BB), mineralocorticoid receptor antagonists (MRA), and more recently angiotensin receptor neprilysin inhibitor (ARNI) for symptomatic patients in the place of ACE or ARB. The neprilysin inhibitor portion of ARNI prevents the breakdown of beneficial natriuretic peptides and vasoactive substances which in combination with RAAS inhibition resulted in significant (26.5 per cent) CVD mortality and hospitalisation reduction. Ivabradine slows heart rate by inhibition of the If channel, digoxin may be considered in symptomatic HF, and SGLT2 inhibitors can be considered in diabetes. SGLT2i are currently awaiting licence following successful CVD outcome trials

demonstrating benefit with or without diabetes. Challenges to achieving optimal target doses include; hyperkalaemia, worsening renal function, contraindications to therapy (eg, beta-blockers in asthma) and symptomatic hypotension.

Implantable cardio-defibrillators (ICD) and cardiac resynchronisation therapy (CRT)

As a primary prevention approach to avoid sudden cardiac death, an ICD is recommended in patients with an LVEF<35 per cent despite three months of optimal medical treatment. Patients with ischaemic disease are at higher risk of arrhythmia than dilated cardiomyopathies. A left bundle branch block in HF patients causes intraventricular and interventricular dyssynchrony, worsening ventricular remodelling, cardiac output and mitral valve insufficiency. CRT reduces this dysschrony,

Volume 7 | Issue 4 | 2021 | Cardiology 30

FIGURE 1: ESC Heart Failure Guidelines (2016)

resulting in improved symptoms and functional capacity. Patients with a QRS duration greater than 130ms on ECG should be considered for CRT rather than ICD. A national policy on the deactivation of devices is currently underway with the Irish Heart Foundation to support non-specialists in discussing the possibility of deactivation at the time of implantation and as the patient’s condition progresses to end of life.

Non-pharmacological measures and self-care

Rest for patients with HF has been debunked in the past two decades with trials such as HF-ACTION recognising the role of physical deconditioning in worsening disease progression and demonstrating the safety of exercise. Furthermore, an appreciation of the role of HF in inadequate peripheral tissue perfusion, muscle alteration, inflammatory responses, and reduced physical capacity has heightened our awareness of sarcopaenia and the need to improve functional capacity. Similar to pharmacological measures, the ESC has deemed exercise a Class 1A

capacity and symptoms, including fatigue. Continuous endurance training is advocated, characterised by moderate intensity in addition to resistance or strength training to prevent muscle wasting. Patients with cardiac devices should start exercise under health professional supervision. Albeit counterintuitive, the challenge is to reach the frailest HF patients as this cohort exponentially benefit from exercise and to encourage participation in exercise groups or cardiac rehabilitation programmes.

Self-care is a fundamental focus of HF management programmes in improving patient outcomes. Self-care is defined as “a process of maintaining health through health promoting and preventive practices”. Patient education is essential in guiding patients and their families through the misconceptions and poor knowledge that this emotive word ‘heart failure’ evokes. The overarching concept of self-care consists of the three key concepts of (i) self-care maintenance (eg, taking medication adherence, regular exercise, and a healthy diet), (ii) self-care

care management (eg, adjusting diuretic dose in response to symptoms).

Self-efficacy influences self-care actions and decisions. Patients with better selfcare have better survival, quality-of-life and psychological well-being. Nurses are instrumental in influencing self-care by educating and motivating patients to see benefits of certain behaviours, by encouraging healthy habits, by harnessing values and beliefs, and promoting confidence. Caregivers and supportive networks are critical to support HF self-care. The more autonomous the patient becomes in relation to self-care, the less involvement is required by health professionals. See sample HF care plan below left. Conversely, increasingly vulnerable patients unable to practice self-care may rely more on carers and health professionals. Patients with frailty would benefit from closer contact with the HF team. Earlier integration of a palliative approach into HF care to improve symptom and device management, advanced care planning and caregiver support, would be advantageous when confronted with the practical, social, and psychological aftermath of end-stage HF.

Conclusion

The complexity of the HF journey is underscored by the high proportion of non-cardiovascular causes of hospitalisation in HF patients. This in itself is a call to action to specialist nurses and practice nurses alike. Aggressive screening and management of co-morbidities needs to become routine practice to not only facilitate good preventive medicine, but also to relieve the sequelae of complex symptom interactions. National drivers of organisation change such as Sláintecare create an opportunity to bridge the secondary primary care divide. Responding to HF complexity is an opportunity for ANPs to develop links in the community and create personalised treatment plans that traverse beyond the medical model of HF guidelines and respond to the human cost of HF with care and compassion. n

References on request

Volume 7 | Issue 4 | 2021 | Cardiology

Coverdine® (perindopril arginine/indapamide/amlodipine) Abbreviated Prescribing Information: Please refer to the Summary of Product Characteristics before prescribing. COMPOSITION* Coverdine 5mg/1.25mg/5mg film-coated tablets contains 5 mg perindopril arginine (per)/1.25 mg indapamide (ind)/5 mg of amlodipine (amlo); Coverdine 5mg/1.25mg/10mg film-coated tablets: 5 mg per/1.25 mg ind/10 mg amlo; Coverdine 10mg/2.5mg/5mg film-coated tablets: 10 mg per/2.5 mg ind/5mg amlo; Coverdine 10mg/2.5mg/10mg film-coated tablets: 10 mg per/2.5 mg ind/10 mg amlo. INDICATIONS* Substitution therapy for treatment of essential hypertension, in patients already controlled with perindopril/indapamide fixed dose combination and amlodipine, taken at the same dose level. DOSAGE AND ADMINISTRATION* One tablet per day, preferably in the morning and before a meal. The fixed dose combination is not suitable for initial therapy. If a change of the posology is required, titration should be done with the individual components. Paediatric population: should not be used. CONTRAINDICATIONS* Dialysis patients. Patients with untreated decompensated heart failure. Severe renal impairment (Clcr < 30 mL/min). Moderate renal impairment (Clcr 30-60 mL/min) for Coverdine 10mg/2.5mg/5mg and 10mg/2.5mg/10mg. Hypersensitivity to the active substances, to other sulfonamides, to dihydropyridine derivatives, any other ACE-inhibitor or to any of the excipients. History of angioedema (Quincke’s oedema) associated with previous ACE inhibitor therapy (see Warnings section). Hereditary/idiopathic angioedema. Second and third trimesters of pregnancy (see Warnings and Pregnancy and lactation sections). Lactation (see Pregnancy and lactation section). Hepatic encephalopathy. Severe hepatic impairment. Hypokalaemia. Severe hypotension. Shock, including cardiogenic shock. Obstruction of the outflow-tract of the left ventricle (e.g. high grade aortic stenosis). Haemodynamically unstable heart failure after acute myocardial infarction. Concomitant use of Coverdine with aliskiren-containing products in patients with diabetes mellitus or renal impairment (GFR < 60mL/min/1.73m²) (see Interaction section), concomitant use with sacubitril/valsartan (see WARNING* and INTERACTIONS*), extracorporeal treatments leading to contact of blood with negatively charged surfaces (see INTERACTIONS*), significant bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney (see WARNING*). WARNINGS* Special warnings: Dual blockade of the renin-angiotensin-aldosterone system (RAAS): ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. Neutropenia/agranulocytosis/thrombocytopenia/anaemia: caution if collagen vascular disease, immunosuppressant therapy, treatment with allopurinol or procainamide, or combination of these complicating factors, especially if pre-existing impaired renal function. Monitoring of white blood cell counts. Renovascular hypertension: increased risk of hypotension and renal insufficiency in patient with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Diuretics may be a contributory factor. Loss of renal function may occur (minor changes in serum creatinine) even in patients with unilateral renal artery stenosis. Hypersensitivity/angioedema, intestinal angioedema: stop treatment and monitor until complete resolution of symptoms. Angioedema associated with laryngeal oedema may be fatal. Concomitant use of mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus): patients may be at increased risk for angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment). Combination with sacubitril/valsartan (contraindicated due to the increased risk of angioedema). Sacubitril/valsartan must not be initiated until 36 hours after taking the last dose of perindopril therapy. Perindopril therapy must not be started until 36 hours after the last dose of sacubitril/valsartan. Concomitant use of other NEP inhibitors (e.g. racecadotril) and ACE inhibitors may also increase the risk of angioedema. Anaphylactoid reactions during desensitization: Caution in allergic patients treated with desensitization and avoid if venom immunotherapy. Temporarily withdrawal of ACE-inhibitor at least 24 hours before desensitization. Anaphylactoid reactions during LDL apheresis: Temporarily withholding ACE-inhibitor prior to each apheresis. Haemodialysis patients: consideration to use dialysis membranes other than high flux or antihypertensive agents other than ACE inhibitors. Primary aldosteronism: use not recommended in patients with primary hyperaldosteronism (not responding to drugs acting through inhibition of the renin-angiotensin system). Pregnancy: no initiation during pregnancy, stop treatment and start alternative therapy if appropriate. Hepatic encephalopathy: stop treatment. Photosensitivity: stop treatment. Precautions for use: Renal function: In certain hypertensive patients without pre-existing apparent renal lesions and for whom renal blood tests show renal insufficiency, stop treatment and restart at a low dose or with one constituent only. Monitoring of potassium and creatinine, after two weeks of treatment and then every two months during therapeutic stability period. If bilateral renal artery stenosis or single functioning kidney: not recommended. Risk of arterial hypotension and/or renal insufficiency (in cases of cardiac insufficiency, water and electrolyte depletion, in patients with low blood pressure, renal artery stenosis, congestive heart failure or cirrhosis with oedema and ascites): start treatment at low doses and increase progressively. Hypotension and water and sodium depletion: Risk of sudden hypotension in presence of pre-existing sodium depletion (in particular if renal artery stenosis): Monitoring of plasma electrolytes, re-establish blood volume and pressure, restart treatment at a reduced dose or with only one of the constituents. Sodium levels: More frequent monitoring in elderly and cirrhotic patients. Potassium levels: Hyperkalaemia: Monitoring of serum potassium if renal insufficiency, worsening of renal function, age (> 70 years), diabetes mellitus, intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis and concomitant use of potassium-sparing diuretics, potassium supplements or potassium salts, or other drugs associated with increases in serum potassium. Hypokalaemia: high risk for elderly and/or malnourished subjects, cirrhotic patients with oedema and ascites, coronary patients, patients with renal failure or heart failure, long QT interval: monitoring of serum potassium. May favor the onset of torsades de pointes, which may be fatal. Calcium levels: hypercalcemia: stop treatment before investigating the parathyroid function. Renovascular hypertension: if renal artery stenosis: start treatment at hospital at low dose; monitor renal function and potassium. Dry cough. Atherosclerosis: start treatment at low dose in patients with ischaemic heart disease or cerebral circulatory insufficiency. Hypertensive crisis. Cardiac failure/severe cardiac insufficiency: Caution if heart failure. Severe cardiac insufficiency (grade IV): start treatment under medical supervision with reduced initial dose. Aortic or mitral valve stenosis / hypertrophic cardiomyopathy: Caution if obstruction in the outflow tract of the left ventricle. Diabetic patients: If insulin dependent diabetes mellitus, start treatment under medical supervision with reduced initial dose; monitor blood glucose during the first month and/or in the case of hypokalaemia. Black people: higher incidence of angioedema and apparently less effective in lowering blood pressure than in non-blacks. Surgery / anaesthesia: stop treatment one day before surgery. Hepatic impairment: Mild to moderate: caution. Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. Stop treatment if jaundice or marked elevations of hepatic enzymes. Uric acid: hyperuricemia: Increased tendency to gout attacks. Elderly: testing of renal function and potassium levels before treatment start. Dosage increase with care. Excipients: sodium-free. INTERACTION(S)* Contraindicated: Aliskiren in diabetic or impaired renal patients, Extracorporeal treatments, Sacubitril/Valsartan. Not recommended: Lithium, Aliskiren in patients other than diabetic or impaired renal patients, Concomitant therapy with ACE inhibitor and angiotensin-receptor blocker, Estramustine, Potassium-sparing drugs (e.g triamterene,amiloride,…), Potassium salts, Co-trimoxazole (trimethoprim/sulfamethoxazole),Dantrolene (infusion), Grapefruit or grapefruit juice. Special care: Baclofen, Non-steroidal anti-inflammatory medicinal products (included acetylsalicylic acid at high doses), Antidiabetic agents (insulin, hypoglycaemic agents), Non-potassium-sparing diuretics and Potassium-sparing diuretics (eplerenone, spironolactone), Racecadotril, mTOR inhibitors (e.g. sirolimus, everolimus, temsirolimus), Torsades de pointes inducing drugs, Amphotericin B (IV route), glucocorticoids and mineralocorticoids (systemic route), tetracosactide, stimulant laxatives, Cardiac glycosides, Allopurinol, CYP3A4 inducers, CYP3A4 inhibitors. To be taken into consideration: Imipramine-like antidepressants (tricyclics), neuroleptics, other antihypertensive agents and vasodilatators, tetracosactide, Allopurinol, cytostatic or immunosuppressive agents, systemic corticosteroids or procainamide, Anaesthetic drugs, Diuretics (thiazide or loop diuretics), Gliptines (linagliptine, saxagliptine, sitagliptine, vildagliptine), Sympathomimetics, Gold, Metformin, Iodinated contrast media, Calcium (salts), Ciclosporine, Atorvastatin, digoxin, warfarin, Tacrolimus, Simvastatin. PREGNANCY AND BREASTFEEDING* Contraindicated during the second and third trimesters of pregnancy and lactation. Not recommended during the first trimester of pregnancy. FERTILITY* Reversible biochemical changes of spermatozoa in some patients treated by calcium channel blockers. DRIVE & USE MACHINES* May be impaired due to low blood pressure that may occur in some patients, especially at the start of treatment. UNDESIRABLE EFFECTS* Very common: oedema. Common: dizziness, headache, paraesthesia, vertigo, somnolence, dysgeusia, visual impairment, diplopia, tinnitus, palpitations, flushing, hypotension (and effects related to hypotension), cough, dyspnoea, abdominal pain, constipation, diarrhoea, dyspepsia, nausea, vomiting, change of bowel habit, pruritus, rash, rash maculo-papular, muscle spasms, ankle swelling, asthenia, fatigue. Uncommon: rhinitis, eosinophilia, hypersensitivity, hypoglycaemia, hyperkalaemia reversible on discontinuation, hyponatraemia, insomnia, mood altered (including anxiety), depression, sleep disorder, hypoaesthesia, tremor, syncope, tachycardia, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), vasculitis, bronchospasm, dry mouth, urticaria, angioedema, alopecia, purpura, skin discoloration, hyperhidrosis, exanthema, photosensitivity reaction, pemphigoid, arthralgia, myalgia, back pain, micturition disorder, nocturia, pollakiuria, renal failure, erectile dysfunction, gynaecomastia, pain, chest pain, malaise, oedema peripheral, pyrexia, weight increased, weight decreased, blood urea increased, blood creatinine increased, fall. Rare: confusional state, blood bilirubin increased, hepatic enzyme increased, psoriasis aggravation. Very rare: agranulocytosis, aplastic anaemia, pancytopenia, leukopenia, neutropenia, haemolytic anaemia, thrombocytopenia, allergic reactions, hyperglycaemia, hypercalcaemia, hypertonia, neuropathy peripheral, stroke possibly secondary to excessive hypotension in high-risk patients angina pectoris, myocardial infarction, possibly secondary to excessive hypotension in high risk patients, eosinophilic pneumonia, gingival hyperplasia, pancreatitis, gastritis, hepatitis, jaundice, hepatic function abnormal, erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis, toxic epidermal necrolysis, Quincke’s oedema, acute renal failure, haemoglobin decreased and haematocrit decreased. Not known: Potassium depletion with hypokalaemia, particularly serious in certain high risk populations, extrapyramidal disorder (extrapyramidal syndrome), myopia, vision blurred, torsades de pointes (potentially fatal), possibility of onset of hepatic encephalopathy in case of hepatic insufficiency, possible worsening of pre-existing systemic lupus erythematosus, electrocardiogram QT prolonged, blood glucose increased, blood uric acid increased. Raynaud’s phenomenon. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) can be considered as a very rare complication associated with ACE inhibitor therapy. OVERDOSE* PROPERTIES* Perindopril is an inhibitor of the angiotensin converting enzyme (ACE inhibitor) which converts angiotensin I to angiotensin II. Indapamide is a sulfonamide derivative with an indole ring, pharmacologically related to the thiazide group of diuretics. Amlodipine is a calcium ion influx inhibitor of the dihydropyridine group (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle

PRESENTATION* Box of 30 tablets of Coverdine 5mg/1.25mg/5mg,

LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. PA0568/024/002-005. Legal Classiﬁcation for Supply: POM. Local Representative in Ireland: Servier Laboratories (Ireland) Ltd. Second Floor, 19 Lr. George’s Street, Dun Laoghaire, Co. Dublin A96 ER84, Ireland . Tel (01) 6638110, www.servier.ie * For complete information, please refer to the complete Summary of Product Characteristics for Coverdine® at www.medicines.ie Date of last revision of text: September 2020 (Date of last approved SmPC: October 2019) Date of preparation: November 2020. 2021C1CDEPressAD. References: 1. Tòth K, on behalf of the PIANIST Investigators. Am J Cardiovasc Drugs. 2014. DOI 10.1007/s40256-014-0067-2. 2. Pall D et al, Hypertonia és Nephrologia. 2012;16(3-4):119-123. 3. Coverdine SmPC October 2019

5mg/1.25mg/10mg, 10mg/2.5mg/5mg and 10mg/2.5mg/10mg. LES

Hypertension – some practical pointers

AUTHOR: Associate Professor Dermot J McCaffrey, Consultant Cardiologist and Heart Failure Specialist, Beacon Hospital, Dublin

When asked to write an article about a topic as large as hypertension, the challenge is to make that article relevant to the doctor whose next patient has high blood pressure (BP) on a routine clinic visit, ie, first presentation with hypertension and how best to proceed.

GPs are often faced with the dilemma of when to prescribe antihypertensives, especially when the patient is sceptical of the benefits and reluctant to start lifelong drug treatment. Hypertension is an asymptomatic condition so to ensure compliance, the patient must understand the purpose of treatment, that it is not simply to lower the BP reading, but to prevent future cardiovascular (CV) events, most concerningly to the patient, of stroke.

The patient needs to understand that any treatment choices are theirs and despite a high BP reading, there is no urgency to starting drug therapy. Any benefits of BP lowering will only be apparent many years later. The purpose of drug treatment is to prevent CV events in the future. If their BP remains high, over years, the small arteries in their brain will hypertrophy in response. This results in gradual lumen narrowing and then, in 15 years, these small arteries will close causing micro strokes, eg, patient may have slurred speech, arm weakness

or be a bit off balance. BP lowering by drugs has been proven to reduce the risk of this happening. Those patients who remain reluctant might agree to a ‘trial of treatment’ for six weeks, followed by an ambulatory blood pressure monitor (ABPM) when they will generally agree to continue treatment after seeing the improved BP. This ‘buy-in’ from patients will improve longterm compliance and outcomes.

Definition: Hypertension is defined as the level of BP at which the benefits of treatment unequivocally outweigh the risks. Although the relationship between BP and CV and renal events is continuous, we need to use cut-off values to guide us in practice.

Prevalence: Hypertension is present in 30to-45 per cent of adults. This rises with age and systolic BP is more predictive of events than diastolic pressure. Isolated systolic hypertension (ISH) is more common in the elderly as they have less compliant, ie, stiffer arteries. Isolated diastolic hypertension (IDH) is seen in a younger cohort, eg, 40s-to-50s, however, a recent study of 5,104 patients showed no association with coronary calcium or CV events in IDH so drug treatment of this condition remains contentious when found in isolation.

Hypertension, however, is rarely an isolated condition. Its effect on CV events is exacerbated by co-existing issues, eg, smoking, dyslipidaemia, diabetes, uric acid, obesity, family history of coronary artery disease (CAD) or hypertension, sedentary lifestyle, early menopause, socioeconomic factors, and sedentary lifestyle. Other factors especially stress, autoimmune conditions (RA/SLE), major psychiatric conditions, atrial fibrillation, kidney disease and obstructive sleep apnoea (OSA) also influence the risk.

Non-drug treatment: Patients should be aware that although ‘lifestyle modification’, such as salt restriction and weight loss does lower BP, it has not been shown to lower CV risk. A recent paper in the International Journal of Obesity showed that a 13 per cent weight loss resulted in risk reductions, including hypertension and type 2 diabetes, but this degree of weight loss is difficult to achieve in practice, ie, an 80kg patient dropping to 69kg.

Absolute vs relative risk

Older people are at a higher risk of CV events and the benefit of antihypertensives is clear in this population. However, a 55-year-old female with BP 154/85mmHg (grade 1 hypertension) with an appropriate nocturnal dip and with no other risks can be reassured that her SCORE risk is less than 1 per cent over 10 years. So she may choose to take an antihypertensive, but there is no evidence of benefit of such treatment.

However, a 55-year-old female smoker with BP 154/85mmHg, cholesterol 6.0 and low HDL 0.9mmol/L , although she still has a low absolute risk of 2 per cent over 10 years, her ‘CV risk age’ is 71-years-old. This concept may encourage a reluctant younger patient to consider risk factor modification, eg, BP lowering. CV risk age is available at www.heartscore.org and requires the patient’s age, gender, smoking status, total cholesterol and HDL.

Volume 7 | Issue 4 | 2021 | Cardiology 34

TABLE 1: Classification of office blood pressurea and definitions of hypertension gradeb (ESC/ESH 2018)

CASE STUDY 1

A 74-year-old man with a left subconjunctival haemorrhage and BP 208/103mmHg at his GP surgery was referred to the emergency department (ED). Medications were aspirin and bisoprolol 1.25mg prescribed 10 years ago for palpitations.

He was given amlodipine 10mg in the ED and referred to a chest pain clinic the following morning. BP 200/100mmHg in both arms,

but the patient was reassured that they were not at any immediate risk of stroke and an ABPM was arranged. On review the following day; ABPM mean BP 116/67mmHg and bradycardia 53bpm. If this patient had been discharged on antihypertensives from the ED, he would have been at a falls risk. NOTE: his BP was 82/41mmHg when asleep at 4am.

35 Cardiology | Volume 7 | Issue 4 | 2021

CASE STUDY 2

A 75-year-old woman with BP controlled on candesartan 16mg for many years is referred with uncontrolled hypertension and nocturnal headaches. Candesartan initially increased to 24mg, but BP remained high. Amlodipine was added, which exacerbated her headaches. Indapamide 1.5mg was added, but caused hyponatraemia. Consultant office visit, BP 200/85mmHg and headaches keeping her awake. ABPM on candesartan 24mg showed mean BP 153/75mmHg with white-coat overlay and especially at 1am, and when trying to find parking. She also had disturbed sleep until 3am. Solpadine recommended for headaches, but to continue candesartan 24mg. Subsequent emergency department (ED) referral as BP 200/90mmHg with GP and family concerned re stroke. BP 234/105mmHg in ED so was given Valium 5mg and amlodipine 5mg. Investigations included a normal CT brain, echo with no LVH, normal ECG, U&E, 24hr urine for catecholamines, urinalysis, BNP, TFTS, and renal Doppler US.

After a more complete history, she reported a wrist sprain six months ago requiring a sling with subsequent painful right shoulder and neck region. She had a tense trapezius muscle and her neck held in flexed position. Cervical spine MRI showed multilevel facet joint degenerative changes, severe in C5-C6 and C6-C7. Her headaches and neck pain responded to amitriptyline 10mg. She was rechallenged with amlodipine 5mg. Discharge BP 140/70mmHg after two good nights’ sleep and review by physiotherapy with neck and shoulder exercise programme. Hypertension resolved on candesartan 24mg and amlodipine 5mg.

The purpose of this case history is to highlight that previously controlled hypertension rarely becomes ‘uncontrolled’ so important to investigate other causes such as pain, chronic stress, insomnia, obstructive sleep apnoea, caffeine, etc.

Measuring BP

Different measurement techniques have better predictive value, and I would rate them from most useful to least, as ABPM > HBPM > office BP > hospital BP. White-coat hypertension is seen in 30-to-40 per cent of patients and in over 50 per cent of the elderly thus in-clinic BP should not guide treatment, but merely be an indication to arrange an ABPM.

ABPM: An accurate ABPM should have at least 70 per cent of readings interpretable and factors such as the nocturnal dip, the percentage loading (target <30 per cent) and

any white-coat effect are all important in analysing the result. Disturbed sleep and periods of tachycardia due to exercise or stress need to be clarified. The mean BP may not reflect the whole picture, so the ABPM needs to be interpreted carefully before drug treatment is prescribed for life.

Patients should be referred for a specialist opinion to rule out secondary hypertension, eg, associated tachycardia, flushing, electrolyte abnormalities, fluid retention or grade 2 hypertension, or <40 years old, or if their hypertension is resistant, or newly uncontrolled hypertension.

Always question compliance and consider phoning the pharmacy to clarify if the full correct prescription is being filled. Some patients may have taken a ‘course’ of antihypertensives and then assumed that the condition was treated.

Why do I have hypertension?

Although salt, obesity, diet, stress and sedentary lifestyle play a role in hypertension, about 35-to-50 per cent of patients have a heterogenous hereditary condition causing their hypertension. This hereditary trait is associated with obesity, diabetes, dyslipidaemia and premature atherosclerosis.

Volume 7 | Issue 4 | 2021 | Cardiology 36

Konverge Plus is indicated for the treatment of essential hypertension as an add on therapy in adult patients whose blood pressure is not adequately controlled on the combination of olmesartan medoxomil and amlodipine taken as dual-component formulation. Konverge Plus is indicated as substitution therapy in adult patients whose blood pressure is adequately controlled on the combination of olmesartan medoxomil, amlodipine and hydrochlorothiazide, taken as a dual-component (olmesartan medoxomil and amlodipine or olmesartan medoxomil and hydrochlorothiazide) and a single-component formulation (hydrochlorothiazide or amlodipine).

Legal Category: POM. Marketing Authorisation Number: PA 865/19/1-5. Marketed by: A. Menarini Pharmaceuticals Ireland. Further information: Available on request from A. Menarini Pharmaceuticals Ireland Ltd, Castlecourt, Monkstown Farm, Monkstown, Co. Dublin or may be found in the SmPC available at www.medicines.ie Date of Item: March 2021 Item Code: IR-KON-06-2021

C M Y CM MY CY CMY K

Explaining hypertension

Hypertension is a condition where a person’s BP settings are ‘slightly off’, like a thermostat in a hotel room that is set to very warm. Although their body thinks that BP 160/90mmHg is appropriate, ie, their carotid baroreceptors aren’t adjusting their BP lower, we have since learnt from the large Framingham epidemiological studies that this level of BP increases their risk of CV events. However, more importantly, we have shown that we can reduce that risk significantly with effective BP lowering with drugs.

What benefit is there from being on antihypertensives? I don’t feel any better

Large trials show a 10mmHg drop in SBP or a 5mmHg drop in DBP translates to a 20 per cent reduction in major CV events, 10-to-15 per cent reduction in mortality, 35 per cent reduction in stroke, 20 per cent reduction in heart attacks, and finally an impressive 40 per cent reduction in heart failure. These data are from an older and higher risk cohort, but those with a lower absolute risk will still benefit significantly.

Lower-risk patients should be made aware that although there is no evidence of benefit in their individual case, ie, the 50-yearold male with BP 150/90mmHg (grade 1 hypertension), that does not mean that there is no benefit, just that his overall risk is so low that it is difficult to show any benefit without recruiting thousands of such patients and following them for many years. The patient will decide if he wishes to take antihypertensives depending on his own level of risk aversion, but with accurate information as a guide.

BP targets

European Society of Cardiology (ESC) guidelines recommend target office BP <140/90mmHg. However, those with CAD benefit if SBP is 130-139mmHg. There is no extra benefit at SBP 120-130 mmHg and actually an adverse outcome if SBP <120mmHg.

Real life BP targets

Older people with hypertension should be

divided into those who are frail and those who are not, rather than using age alone as the criteria to treat. Not only is this common sense, but also trial data show that those who are frail are at an increased falls risk if their BP is too tightly controlled so aim for BP <140/80mmHg. Patients at significant falls risk were excluded from the large studies, however in the HYVET trial hypertensive drug withdrawal had worst outcomes. Therefore, when managing hypertension of the older patient, there is a fine balance between reducing CV events and not increasing their falls risk.

Hypertension and headaches? Chicken or

egg?

It is important to be aware that there is little evidence to show an association between mild or moderate hypertension and headaches. Headaches are associated with pre-eclampsia, eclampsia, pheochromocytoma and hypertensive crisis, eg, hypertensive encephalopathy. However, most commonly, it is the headache that needs to be addressed when patients present with hypertension.

Treating hypertension: Which antihypertensive agent is another question for another article, but is influenced by many factors such as concomitant CAD, diabetes, renal or heart failure which all influence drug choice. Also, drug tolerance is influenced

by issues such as venous disease and ankle swelling (CCB), incontinence (diuretics), and cold peripheries (BB) so a lot of factors influence the optimal drug choice and dose needed to treat hypertension and therefore the regime will have to be tailored to the individual patient in front of you. There should not be a sense of urgency in initiating treatment as the aim is to get the patient to their target BP over weeks or months, not days. Usually this will be achieved on a combination of medications and hopefully with little or no side effects. We are fortunate nowadays that we have a large number of drug combinations which have been proven to be both effective in reducing hypertension to target levels and which are well tolerated and with placebo level side-effects.

In summary

The biggest decision when managing a patient with hypertension is firstly confirming that they definitely have hypertension. Secondly, is their hypertension at a level which warrants lifelong drug treatment and finally, we need to ask ourselves, what are we trying to achieve and can we explain that clearly to the patient to help their understanding and improve long-term compliance and ultimately, reduce their stroke and CV event rates, which when it comes down to it, is the whole purpose of what we are trying to achieve. n

References on request

Volume 7 | Issue 4 | 2021 | Cardiology 38

FIGURE 1: Core drug treatment strategy for uncomplicated hypertension. The core algoritm is also appropriate for most patients with HMOD, cerebrovascular disease, diabetes, or PAD. ACEi=angiotension-converting enzyme inhibitor; ARB= angiotensin receptor blocker; CCB=calcium channel blocker; HMOD = hypertension-mediated organ damage; MI= myocardial infarction; od=omni die (every day); PAD=peripheral artery disease (ESC/ESH 2018)

For

matters in medicine AVAILABLE IN PRINT AND DIGITAL

all that

Cardiac amyloidosis: Overview, diagnosis, and management

TRUE/FALSE QUESTIONS

1. A DCCV for treatment of atrial arrhythmias should be done under TOE guidance in patients with cardiac amyloidosis.

True or false?

2. CHA2DS2-VASc score can be applied to patients with atrial arrhythmias and cardiac amyloidosis.

True or false?

3. 1.1 per cent of the population in Donegal are carriers for the hereditary ATTR variant Thr60Ala. True or false?

4. Low voltage QRS amplitude changes on ECG are an unpredictable marker of cardiac amyloidosis.

True or false?

5. Systolic function is preserved in cardiac amyloidosis. True or false?

6. Elderly patients with preserved ejection fraction heart failure, evidence of left ventricular hypertrophy on Echo and a history of bilateral carpal syndrome should have investigations for the presence of ATTRwt. True or false?

7. Initial investigation in the diagnosis of ATTR cardiac amyloidosis involves the use of DPD scans.

True or false?

8. Before proceeding with further investigations to confirm CA, out-ruling AL amyloidosis is very important. This involves the evaluation of serum free light chain ratio and serum protein electrophoresis to detect potential a monoclonal protein.

True or false?

9. Treatment of ATTR CA requires the use of B-Blockers, ACEI and MRA.

True or false?

10. siRNA therapies are urrently approved for the treatment of ATTR CA.

True or false?

Check your answers to these questions and answer five MCQs about cardiac amyloidosis in this free CPD module for doctors on www. doctorcpd.ie. Successful completion of this module will earn you 2 CPD points.

LEARNING OBJECTIVES OF THIS MODULE:

 Understand the principal causes (AL amyloidosis and ATTR) and underlying pathophysiology of cardiac amyloidosis.

 Identify patients to screen for cardiac amyloidosis and the subsequent diagnostic process.

 Develop insight into the management of cardiac amyloidosis and its underlying causes.

Cardiac amyloidosis (CA) is a pathological condition that results from the deposition of abnormal amyloid fibrils in the myocardium. Amyloid fibrils are aggregated misfolded insoluble protein polymers comprising identical monomer units. Once formed, fibrils are deposited in different tissues causing ‘amyloidosis’, often leading to eventual organ dysfunction. All amyloid fibrils have apple-green birefringence in the presence of Congo red stain under polarised light.

Although there are many types of amyloidosis, for the purpose of this article we will concentrate on the principal two causes of systemic amyloidosis: Light chain (AL) amyloidosis and transthyretin amyloidosis (ATTR), both of which commonly have cardiac involvement, leading to CA.

Although both AL and ATTR have some clinical overlap they are important

Volume 7 | Issue 4 | 2021 | Cardiology 40

AUTHORS: Dr Neasa Starr, Advanced Heart Failure Registrar, and Prof Niall Mahon, Consultant Cardiologist, Mater University Hospital, Dublin

to distinguish early as they require different management approaches based on their differing pathophysiology and ultimately have very different prognoses, particularly if AL amyloidosis is untreated or treatment is delayed.

Pathophysiology AL amyloidosis

AL amyloidosis has an incidence of 0.8 per 100,000. Males are more commonly affected (57 per cent) and the median age at diagnosis is 60 years old . The pathogenesis of AL amyloidosis arises in the bone marrow as clonal plasma cells produce excess misfolded light chains. In the majority of cases an abnormal ratio is created by excess production of lambda light chains. Deposition of light chain fibrils in various tissues, affects organs such as the kidneys (74 per cent), liver (27 per cent) and peripheral nerves (22 per cent). In addition, 60 per cent of patients with AL amyloidosis also develop cardiomyopathy as light chains deposited in the myocardium are directly myocytotoxic. With cardiac involvement, median survival is less than 12 months, indicating the importance of a timely diagnosis and treatment. Following induction of clonal remission and treatment with autologous stem cell transplant, however, two-year survival is increased to 94 per cent.

ATTR

Unlike AL amyloidosis, ATTR involves transthyretin (TTR) tetramers, which are produced and released predominantly by the liver to transport thyroxine and retinol (vitamin A). There are two forms of ATTR; hereditary (or variant) ATTR (hATTR) due to a single genetic abnormality in the TTR gene, and wildtype ATTR (wtATTR) which is related to the ageing process.

Under normal circumstances TTR monomers produced by the liver immediately bind to form a tetramer that acts as the thyroxine transporter. Although the exact mechanism is different according to the subtype

(ie, wild-type or hereditary), in ATTR an unstable tetramer is produced, which degrades into individual monomer proteins. These monomers ultimately unite to form insoluble fibrils, which are deposited in various tissues, such as the extracellular space of the myocardium, thus causing the clinical phenotype.

Hereditary ATTR

The TTR gene is located on chromosome 18. The mutated TTR gene responsible for hATTR causes a single mutation in one of the 127 amino acids that form the TTR tetramer. This single mutation allows the TTR tetramer to become unstable, thus unfold and aggregate to form insoluble amyloid fibrils. In

neuropathy. Autonomic neuropathy can result in varying symptoms such as orthostatic hypotension, constipation/ diarrhoea, gastroparesis and urinary incontinence/retention. Although neurological involvement is more commonly described in this patient cohort, cardiac amyloidosis may also develop. Compared to the Val30Met variant, 97 per cent of those with Val122IIe have cardiac involvement whilst more than 50 per cent develop carpal tunnel and peripheral neuropathy.

the heart, TTR amyloid fibrils are deposited in the extracellular matrix of the myocardium. Although it is an autosomal dominant condition, its phenotype has a heterogenous penetrance. Symptom severity and rate of progression therefore varies between patients.

Although there are over 130 known TTR mutations, the three most common worldwide are Val30Met, Val122IIe and Glu89Gln. The genetic mutation often determines the principal organs affected and therefore the clinical course. Val30Met is most common worldwide with high incidences in Portugal, Spain, and France. It predominantly causes both a peripheral and autonomic

In Ireland and the UK, Thr60ala is the most common hATTR variant. It is most commonly found in the north west of Ireland. In county Donegal it is believed 1.1 per cent of the population are carriers of the variant (Reilly et al, 1995). Thr60Ala hATTR predominantly affects the heart and autonomic nervous system, with less than 25 per cent experiencing peripheral neuropathy. Although Thr60Ala has a later symptom onset (median onset 63 years of age) than Val30Met which often occurs in the third decade, Thr60Ala has a worse prognosis as it preferentially affects the heart. When comparing survival between the two variants in a Swedish and UK study, median survival from symptom onset was 12 years in Val30Met patients compared to 8.2 years in the Thr60Ala group (p=0.002).

hATTR is a progressive disease and if left untreated has a survival of three-to-15 years post clinical presentation.

Wild-type ATTR

The incidence of wtATTR, previously known as ‘senile systemic amyloidosis’, is believed to be present in approximately 10 per cent of those with heart failure with preserved ejection fraction (HFpEF). The condition increases with age and in autopsy studies of patients aged over 80 years, the incidence of CA as a result of wtATTR was as high as 25 per cent. In general, the age of onset is most commonly above 65 years of age, occurring mostly in males.

41 Cardiology | Volume 7 | Issue 4 | 2021

As it is often associated with common comorbidities in the elderly population with subtle symptoms, wtATTR is generally under investigated and therefore under-diagnosed

As it is often associated with common comorbidities in the elderly population with subtle symptoms, wtATTR is generally under investigated and therefore under-diagnosed. A high index of suspicion needs to be had to investigate and diagnose its presence. Patients with the highest incidence include those with a history of HFpEF, bilateral carpal tunnel syndrome, spinal stenosis, biceps tendon rupture, conduction abnormalities and atrial arrhythmias such as atrial fibrillation. Unlike hATTR, peripheral and autonomic neuropathy are rarely features of wtATTR.

In wtATTR, despite the lack of TTR mutations the TTR tetramer similarly dissociate, misfold and aggregate into amyloid fibrils, which are deposited in the extracellular matrix of the heart. Although the exact reason for tetramer protein destabilisation is unknown, the process is associated with an increase in age. It often has a slowly progressive clinical course for many years before eventual rapid deterioration.

Clinical investigations ECG

The typical ECG findings found in CA are low voltage complexes (defined as <0.5mV amplitude in limb leads and <1.5mV in precordial leads when S1

of lead V1 is added to the R wave in V5 or V6) and often signs of a pseudoinfarct (such as q-waves) particularly in those with AL amyloid. These features are commonly absent in CA however, occurring in only 25 per cent of those with ATTR and 45 per cent in AL amyloidosis, thus having a poor negative predictive value.

atrial fibrillation and AV conduction abnormalities.

Echo

Transthoracic echocardiography (TTE) is an important tool used to investigate a potential diagnosis of CA and is also used to monitor patients with confirmed diagnosis. The most common finding on Echo in this patient cohort is LVH due to amyloid fibril deposition within the myocardium. LVH is often symmetrical but can also be asymmetric, particularly in ATTR. Sometimes LVH in CA has a ‘sparkling’ appearance on TTE due to the fact fibril deposition occurs in the extracellular matrix of the myocardium.

Amyloid fibril accumulation in the myocardium causes a restrictive cardiomyopathy. In early stages of the disease this translates into mildmoderate diastolic dysfunction with preserved left ventricular (LV) ejection fraction (EF). Despite preserved EF, evidence of systolic dysfunction can be detected using cardiac myocardial strain during TTE. Strain is a technique that measures subtle changes in systolic function by measuring longitudinal shortening of points along the LV during systole giving a ‘Global Longitudinal Strain’ (GLS) value. Unlike other cardiomyopathies, the pattern of systolic dysfunction in CA detected by myocardial strain shows preserved function in the ventricular apex but reduced longitudinal movement in the base of the heart, leading to ventricular dysfunction that is ‘apical sparing’ (Image 2).

Generally, patients with an ECG showing a lack of evidence for left ventricular hypertrophy (LVH) compared to the amount observed on Echo should raise clinical suspicion for amyloidosis (Image 1), particularly in those with wtATTR.

Other abnormalities seen on ECG in CA include atrial arrhythmias such as

Often with time, as amyloidosis and its subsequent restriction progresses, diastolic dysfunction worsens with an eventual reduction in LV systolic function.

Other typical features seen on Echo in amyloidosis include:

 Bi-atrial enlargement

 Intra-atrial septal thickening

 Thickening of the mitral and aortic valve leaflets

Volume 7 | Issue 4 | 2021 | Cardiology 42

IMAGE 1: Despite an echo displaying severe concentric LVH due to hATTR, there is a disproportionate lack of LVH as per voltage criteria displayed on the same patient’s ECG as depicted above.

As it is often associated with common comorbidities in the elderly population with subtle symptoms, wtATTR is generally under investigated and therefore under-diagnosed

SUSPECT ATTR-CM

(TRANSTHYRETIN AMYLOID CARDIOMYOPATHY)

A LIFE-THREATENING DISEASE THAT CAN GO UNDETECTED

Life-threatening, underrecognized, and underdiagnosed, ATTR-CM is a rare condition found in mostly older patients in which misfolded transthyretin proteins deposit in the heart.1-7 It is vital to recognize the diagnostic clues so you can identify this disease.

CONSIDER THE FOLLOWING CLINICAL CLUES, ESPECIALLY IN COMBINATION, TO RAISE SUSPICION FOR ATTR-CM AND THE NEED FOR FURTHER TESTING

heart failure with preserved ejection fraction in patients typically over 60 years old5-7

to standard heart failure therapies (ACEi, ARBs, and beta blockers)8-10

between QRS voltage and left ventricular (LV) wall thickness11-13

of carpal tunnel syndrome or lumbar spinal stenosis3,8,14-20

showing increased LV wall thickness6,13,16,21,22

H FpEF I NTOLERANCE DISCORDANCE DIAGNOSIS E CHO N ERVOUS SYSTEM

LEARN HOW TO RECOGNIZE THE CLUES OF ATTR-CM AT:

S U S P E C T A N D D E T E C T . I E

—autonomic nervous system dysfunction-including gastrointestinal complaints or unexplained weight loss6,16,23,24

MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213.

Elliott P, Comenzo R,

M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. 3. Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290. 4. Pinney JH, Whelan CJ, Petrie A, et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098. 5. Mohammed SF, Mirzoyev SA, Edwards WD, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2(2):113-122. 6. Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172.

7. González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585-2594. 8. Narotsky DL, Castano A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10. 9. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016;22(12):996-1003. 10. Castaño A, Drach BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178. 11. Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982;49:9-13. 12. Cyrille NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114(7):1089-1093. 13. Quarta CC, Solomon D, Uraizee I, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014;129(18):1840-1849. 14. Connors LH, Prokaeva T, Lim A, et al. Cardiac amyloidosis in African Americans: Comparison of clinical and laboratory features of transthyretin V122I amyloidosis and immunoglobulin light chain amyloidosis. Am Heart J. 2009;158(4):607-614. 15. Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58-63. 16. Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203-1212. 17. Sperry BW, Reyes BA, Ikram A, et al. Tenosynovial and cardiac amyloidosis in patients undergoing carpal tunnel release. J Am Coll Cardiol. 2018;72(17): 2040-2050. 18. Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. 19. Yanagisawa A, Ueda M, Sueyoshi T, et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol. 2015;28(2):201-207. 20. Sueyoshi T, Ueda M, Jono H, et al. Wild-type transthyretin-derived amyloidosis in various ligaments and tendons. Hum Pathol. 2011;42(9):1259-1264. 21. Phelan D, Collier P, Thavendiranathan P, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98(19):1442-1448. 22. Ternacle J, Bodez D, Guellich A, et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging 2016;9(2):126-138. 23. Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76. 24. Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131.

The health information contained in this ad is provided for educational purposes only. Date of Preparation: February 2021 GCMA code: PP-RDP-IRL-0105

References 1. Sipe JD, Benson 2. Maurer MS, Semigran

IMAGE 2: This is an example of ‘apical sparing’ in ATTR as depicted by Global Longitudinal Strain (GLS) calculated during an echocardiogram. Normal function gives a GLS value less than -20. Values approaching ‘0’ therefore represent worsening ventricular function. This image represents each segment of the left ventricle. The cardiac base occupies the outermost circumference (outer six segments) of the image, whilst the cardiac apex is represented at the centre. As seen by the values calculated by GLS, the basal segments of the heart in this patient with hATTR have significantly reduced function, whilst the apical regions are near normal. This is a feature typically detected on echo in CA as the systolic dysfunction is ‘apical sparing’.

An incidental finding of a left atrial appendage (LAA) thrombus is not an uncommon finding in CA. This can also occur in the absence of atrial arrhythmias, a feature most commonly seen in AL amyloidosis.

CMR

Although for many centres cardiac MRI (CMR) is a limited resource, increasing availability internationally is improving its utility in the diagnosis of CA. CMR with late gadolinium enhancement (LGE) is completed with T1 mapping where available. CMR contributes to the quantification of LVH by quantifying LV wall thickness and LV mass index, which are generally both increased in CA.

LGE allows visualisation of amyloid deposition in the myocardium and is almost always present in patients

with CA. A global subendocardial pattern of LGE is generally typical of AL amyloidosis but it can also have a transmural distribution particularly in ATTR. Despite the utility of the pattern of LGE in contributing towards a potential diagnosis of CA, it is not specific to the condition so has not obviated the need for further investigations to confirm the diagnosis.

Diagnosis

All patients presenting with heart failure and features of CA on either TTE or CMR should have initial testing that out-rules AL amyloidosis as a potential cause of CA. This includes the completion of both a free light chain assay and serum and urine protein electrophoresis (S/UPEP) with immunofixation to ensure the absence of monoclonal proteins. If either of these tests are abnormal, urgent biopsy is

required to investigate the presence of AL amyloidosis thus facilitating the initiation of appropriate therapy.

If these tests are negative however, the patient can go on to have a radionuclide bone scintigraphy test, usually in the form of a DPD (99m-labelled-3,3diphosphono-1,2-propanodicarboxylic acid) scan in Ireland. Since the publication of a sentinel paper in 2016 (Gillmore et al, 2016) radionuclide bone scintigraphy has been shown to diagnose ATTR CA with greater than 98 per cent certainty (Gillmore et al, 2016) once AL amyloidosis has been ruled out. The utility of bone scintigraphy avoids the need for an invasive endomyocardial biopsy (EMB) and its associated risks (such as cardiac tamponade and arrhythmia) to diagnose ATTR CA.

Radionuclide bone scintigraphy scan results are given according to a scale (Perugini 0-3) based on the level of radionuclide uptake in the heart as compared to the contralateral chest. Grade 0 indicates an absence of CA whereas grades 2-3 are diagnostic for its presence. If there is a very high index of suspicion for ATTR despite low uptake on bone scintigraphy, an EMB can be performed to confirm the diagnosis.

In order to determine the type of ATTR CA diagnosed by a bone scintigraphy scan, ie, either wild type or hereditary ATTR, patients should proceed to have transthyretin gene sequencing in the form of serum sample analysis. Patients with a detected TTR variant will therefore have a diagnosis of hATTR.

Role of biomarkers in ATTR

Since its publication in 2018 the Gillmore staging system is now widely used to risk stratify patients with a diagnosis of ATTR (both wtATTR and hATTR). The staging system puts patients into one of three tiers as determined by their NT-pro-BNP (brain derived natriuretic protein) level and estimated glomerular filtration rate

Volume 7 | Issue 4 | 2021 | Cardiology 44

(eGFR). In the initial study, it was found that stage 1 translated into a median survival of almost six years (69.2 months), four years (median survival 46.7 months) for stage 2, and two years for stage 3 (median survival 24.1 months).

In stage 1, the NT-pro-BNP level is less than or equal to 3,000pg/ml and an eGFR greater than or equal to 45ml/min. In stage 3 the NT pro BNP is greater than 3,000pg/ml and eGFR less than 45ml/min, whilst stage 2 has only one of these values present.

As the staging system is correlated with median survival it is a useful consideration when deciding upon the optimal drug treatment for a patient. It is also a useful method to monitor treatment response, as well as helping to guide appropriate management of comorbidities.

Although not included in the Gillmore staging, troponin levels are generally monitored in patients with CA. Elevated troponin levels are associated with increased risk of mortality in acute heart failure and cardiomyopathies. Similarly, it has been proven to predict mortality when elevated in CA. Although it does not have a role in the diagnosis of CA, it is another useful biomarker used for disease surveillance.

Treatment

Treatment of CA is focused on the following:

 Disease-modifying medications

 Management of symptomatic heart failure

1. Disease modifying drugs:



AL amyloidosis

Due to differing pathophysiology, unsurprisingly, prognostic treatment of AL amyloidosis is very different to that of ATTR. In AL amyloidosis chemotherapy is urgently initiated to inhibit the plasma cell dyscrasia and eventual need for autologous stem cell transplant is common.

 ATTR

The various treatments for ATTR act upon one of three stages involved in the pathogenesis of CA:

• TTR tetramer stabilisation

• Inhibition of TTR production by the liver via RNA interference

• Amyloid fibril disruption

gastrointestinal bleeding and renal impairment, patients require ongoing surveillance while on it.

Inhibition of TTR production by the liver via RNA interference

TTR tetramer stabilisation

At present the majority of patients are treated with therapies that act to stabilise the TTR tetramer, including the drugs tafamidis and diflunisal. Since the publication of the ATTR-ACT trial (Maurer et al, NEJM, 2018) patients with CA secondary to ATTR (both wild-type and hereditary) and New York Heart Association (NYHA) I-III heart failure symptoms may be treated with tafamidis.

Tafamidis selectively binds to the thyroxine binding site on TTR thus stabilising the protein to prevent fibril formation. In the ATTR-ACT trial, when compared to placebo, tafamidis significantly reduced the combined risk of all-cause mortality and cardiovascular-related hospitalisations after 30 months of treatment. The improved survival benefit began to occur after 18 months of treatment.

Diflunisal, another TTR stabiliser, is an NSAID used in patients with hATTR CA, following a randomised controlled trial (RCT) in 2013 that proved symptomatic improvement in patients with peripheral neuropathy. As side-effects include

Recently new therapeutic options have been developed to treat CA. Through the development of small interfering RNA (siRNA) drugs, TTR production can be directly inhibited in the liver. siRNAs directly inhibit TTR messenger RNA thus inhibiting translation into the TTR protein. To date patisiran (an siRNA given by IV infusion every three weeks) has been approved for use in patients with hATTR with polyneuropathy (Apollo trial). Due to subsequent analysis from the initial Apollo trial, which showed a 46 per cent reduction in all-cause mortality and cardiac hospitalisations, the potential use of patisiran in patients with CA is being tested in a phase 3 RCT (Apollo B). Vutrisiran is another siRNA given by subcutaneous injection every three months that is at phase 3 drug trial stage, evaluating its benefit in patients with polyneuropathy (Helios A) and CA (Helios B) in patients with both forms of ATTR (wild type and hereditary).

Amyloid fibril disruption

There are no approved drugs that target amyloid fibril disruption available for use at present, but there are drugs currently being tested for potential future use. This includes combined drug therapy with doxycycline and tauroursodeoxycholic acid (TUDCA) and is presently under investigation in a phase 3 RCT for use in patients with hATTR.

Transplantation

As hATTR is due to abnormal TTR production by the liver, patients with the condition without significant CA may be candidates for a liver transplant. If this is completed, however, patients often require treatment with TTRstabilising medication in an effort to reduce the development of cardiac

45 Cardiology | Volume 7 | Issue 4 | 2021

In Ireland Thr60Ala is the most common variant of hATTR and it is believed that 1.1 per cent of the population in Donegal are carriers

amyloidosis, which may occur despite liver transplantation. With the recent development of medication that inhibits TTR production by the liver, the need for liver transplant may be reduced in the future. Finally, in exceptional circumstances patients with advanced heart failure as a result of ATTR CA may also be candidates for heart or double organ (heart-liver) transplantation.

2. Heart failure management:

Irrespective of the cause of CA, heart failure symptoms are managed with diuretic use in the form of loop diuretics or mineralocorticoid receptor antagonists (MRA). Almost all patients with CA require diuresis but the response should be carefully monitored. Due to diastolic dysfunction and therefore reduced ventricular compliance, significant preload reduction due to over-diuresis should be avoided.

Due to the restrictive cardiomyopathy resulting from CA and potential autonomic neuropathy, afterload reducers such as angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or angiotensin receptor II-neprilysin inhibitors (ARNI) are of no proven benefit and often poorly tolerated. Similarly, beta blockers should be used with caution due to their negative chronotropic effects. Bradycardias are often not tolerated as a higher heart rate is required to maintain an optimal cardiac output.

When considering anticoagulation initiation in patients with CA the CHA2DS2-VASc score does not apply. Due to the high risk of thrombus formation in the left atrial appendage (LAA) in CA, there should be a low threshold for anticoagulation use in this patient group.

It is important to note that all patients undergoing direct current cardioversion (DCCV) for an atrial arrhythmia should have a transoesophageal echocardiography (TOE) first to out-rule

an LAA thrombus, even if the patient is appropriately anticoagulated. In one study, 26 per cent of amyloid patients had an LAA thrombus detected by TOE prior to DCCV. Of these patients, 46 per cent had a persistent thrombus despite appropriate therapeutic anticoagulation directly resulting from reduced atrial function secondary to CA rather than anticoagulant failure.

Summary

 Cardiac amyloidosis resulting from transthyretin amyloidosis is an under investigated cause of heart failure. It has a high prevalence within certain patient cohorts and has been shown to occur in 10-to-15 per cent of patients with preserved ejection fraction heart failure.

 There are two forms of transthyretin amyloidosis – hereditary (autosomal dominant and due to a single gene mutation) and wild type (previously known as senile systemic amyloidosis). There are different patterns of organ involvement and resulting symptoms according to the subtype of ATTR.

 In Ireland Thr60Ala is the most common variant of hATTR and it is believed that 1.1 per cent of the population in Donegal are carriers for this genetic mutation.

 ATTR can now be diagnosed using DPD scans in patients with a high index of suspicion based on echocardiogram or CMR. Importantly, however, AL amyloidosis must be out-ruled by analysing a serum free light chain ratio and serum/urine electrophoresis (to ensure no monoclonal band) before patients proceed to have a DPD scan.

 Cardiac amyloidosis causes a restrictive cardiomyopathy with left ventricular hypertrophy and an initial preserved ejection fraction that deteriorates to a reduced ejection fraction as the disease progresses. There is also a high incidence of atrial arrhythmias and conduction

abnormalities often necessitating the need for a pacemaker.

 For patients with atrial flutter or atrial fibrillation, the CHA2DS2-VASc score does not apply and patients should be considered for anticoagulation due to high risk of thrombus formation.

 All patients undergoing a DCCV for atrial arrhythmias should have it done under TOE guidance due to the high risk of thrombus formation and persistence in the left atrium despite anticoagulation. This increased thrombus risk is due to abnormal atrial function as a direct consequence of cardiac amyloidosis rather than anticoagulant failure.

 Treatment of ATTR focuses on either reducing production of TTR through siRNA treatments (patisiran or vutrisiran) or TTR stabilisation (tafamidis and diflunisal). siRNA therapies have been proven to benefit patients with ATTR-induced peripheral neuropathy, but phase 3 RCTs investigating their use in cardiac amyloidosis are ongoing at present. Diflunisal is an NSAID available for use in patients with a predominate peripheral neuropathy, and tafamidis is available for those with early stage ATTR cardiac amyloidosis. n References

Volume 7 | Issue 4 | 2021 | Cardiology 46

on request and at

Test your knowledge on cardiac amyloidosis by completing this module on www.doctorcpd.ie.

www.doctorcpd.ie

Management of in-stent restenosis

Pharmacy and Biomolecular Sciences, RCSI, Dublin

KEY POINTS

 The introduction of drug-eluting stents (DES) was a breakthrough innovation for the treatment of patients with obstructive coronary artery disease.

 The rate of clinical restenosis after stenting with DES is less than 5 per cent at one year in unselected patients undergoing percutaneous coronary intervention; at 10 years follow-up it may be as high as one-in-five.

 Lesions in smaller coronary vessels of longer length, and in patients with diabetes mellitus are those at highest risk of restenosis.

 Management of in-stent restenosis

CASE REPORT

A 74-year-old patient presented with recurrent chest pain two years after complex percutaneous intervention with implantation of multiple overlapping DES in the right coronary artery. Cardiac biomarkers were negative, ECG showed no acute changes. Left ventricular function was preserved on echocardiography.

The patient underwent repeat coronary angiography, which showed no obstructive disease in the left coronary artery and multifocal in-stent restenosis in the proximal and mid right coronary artery (Figure 1, Panel A). Intravascular imaging with optical coherence tomography (OCT) showed good stent expansion throughout the stented segment with no evidence of stent fracture (Figure 1, Panel B).

The advent of drug-eluting stent (DES) implantation was an important development in the evolution of treatment of patients with obstructive coronary artery disease. Controlled elution of drug from the stent backbone over the initial 30-to-60 days postimplantation significantly reduces the extent

depends critically on a thorough understanding of the underlying cause; evaluation with intravascular imaging during angiography can give additional actionable information.

 Mechanical causes such as stent underexpansion require specific measures such as correction with high-pressure balloon dilation or intracoronary ultrasonic shock therapy; biological causes such as neointimal hyperplasia can be treated with standard or cutting balloon dilation.

 After the lesion has been successfully re-dilated, angioplasty with drug-coated balloon may be used to avoid the need to implant additional stent layers.

than 5 per cent.1 In fact, a meta-analysis of 158 trials showed a mean rate of restenosis at 12 months of around 2.5 per cent.2 However, rates of restenosis tend to increase over time and clinical trials with long-term follow-up out to five-to-10 years show the ongoing accrual of adverse clinical events related to restenosis; such that at 10 years, up to one-in-five patients required a repeat intervention in the treated segment. This is important as most patients with obstructive coronary disease undergoing percutaneous intervention have good mid-term prognosis and life expectancy.

Aetiology of restenosis

The patient underwent direct follow-on angioplasty with re-dilation of the stenosed segments with high pressure non-compliant balloons, inflated to 14 atmospheres (Figure 1, Panel C). Interim angiographic result was satisfactory, so the patient preceded to treatment with a single paclitaxel coated balloon, inflated to 12 atmospheres for 60 seconds (Figure 1, Panel D). The acute result was good, showing significant tissue disruption inside the stent on OCT (Figure 1, Panel E/F). Because of the high risk of recurrent restenosis, the patient underwent scheduled repeat angiography at six months, which showed an excellent durable result in the intervened segment angiographically and on OCT imaging (Figure 2, Panel A and B).

and impact of neointimal hyperplasia, the dominant cause of stent failure after stenting. In clinical trials with broad inclusion criteria, enrolling patients representative of those seen in routine practice, rates of clinically significant restenosis requiring repeat intervention within the first year are less

Causes of in-stent restenosis can broadly be considered as either mechanical or biological. Common mechanical causes include stent under-expansion, geographic miss (where the full extent of the index lesion was not completely covered), or stent fracture (caused by metal fatigue). Biological causes include neointimal hyperplasia, which may be related to relative resistance to the drug eluted from the stent backbone, or in-stent neoatherosclerosis, which is due to the re-accumulation of plaque inside the stented segment.

Intravascular ultrasound is critical to the understanding of the aetiology of in-stent restenosis. Interrogation of the re-stenosed vessel with either intravascular ultrasound (IVUS) or OCT imaging can generally confirm whether or not mechanical causes, which may require specific intervention, are present and if not, the dominant tissue type causing biological restenosis.

Treatment algorithm

A number of different treatment algorithms exist outlining approaches to the management of in-stent restenosis. One such algorithm has been published by the European Association of Percutaneous Cardiac Intervention.3 In a subset of patients

47 Cardiology | Volume 7 | Issue 4 | 2021

AUTHOR S : Prof Robert A Byrne, Consultant Cardiologist;1,2 Nial Blake, BMBS,1 and Dr Róisín Colleran, Consultant Interventional Cardiologist; 1,2, 1 Cardiovascular Research Institute, Mater Private Hospital, Dublin, Ireland; 2School of

– for example those with recurrent stent failure or left main stem stent failure –bypass surgery may be considered. However, in the majority of cases a percutaneous approach is preferred, at least initially. There are three key steps to management in this situation:

1. Understanding the mechanism of stent failure;

2. Lesion preparation/re-dilation;

3. Final strategy/destination therapy.

Type of lesion preparation is dependent on the identified aetiology. For example, in a case of focal stent under-expansion, focused treatment with high-pressure non-compliant balloon dilatation may facilitate correction of under-expansion that went unrecognised at the time of initial stent implantation. In occasional cases with under-expansion due to severe underlying vessel calcification, disruption of the deep calcium with intravascular ultrasonic shockwave therapy has shown promise in recent clinical trials. In cases of biological in-stent restenosis, cutting or scoring balloons are useful to disrupt tissue and facilitate repeat dilatation; in addition they may enhance the efficacy of subsequent drug-coated balloon angioplasty by facilitating uptake of the active drug

into the plaque and vessel wall. Once the lesion has been successfully dilated, the final strategy for destination treatment is chosen.

In principle, there are two main options for destination therapy: Either repeat stenting with another DES or angioplasty with a drug-coated balloon. In certain situations the choice is straightforward. For example, where stent fracture due to metal fatigue was the dominant mechanism, or a gap is identified between two previously implanted stents, this is best addressed with implantation of a new DES. In other cases, however, either strategy may be chosen.

Ten randomised clinical trials have been conducted comparing outcomes of patients treated with drug-coated balloon angioplasty versus repeat standing with DES. Investigators in our research group recently collected data from the principal investigators of all 10 trials and combined them in a single data set known as the DAEDALUS study.4 The main finding of this large pooled analysis was that repeat stenting within DES was marginally more effective than angioplasty with drug-coated balloon. Against this, however, the rate of adverse safety events represented by the composite

endpoint of death or myocardial infarction tended to favour drug-coated balloon angioplasty. In our practice, in suitable patients, we tend to prefer angioplasty with a drug-coated balloon, at least in the first instance of in-stent restenosis, with repeat stenting reserved for patients with more complex or diffuse disease patterns or those who fail drug-coated balloon therapy and re-present with a second restenosis.

Considerations regarding dual antiplatelet therapy

Dual antiplatelet therapy (DAPT) after repeat percutaneous coronary intervention is not dissimilar to that recommended in patients undergoing PCI for de novo atherosclerotic disease. If presentation at the time of detection of restenosis was with acute coronary syndrome, generally 12 months of DAPT with aspirin and a P2Y12 inhibitor is recommended; if the patient’s bleeding risk is significantly elevated, a shorter therapy of around six months is recommended. In patients with restenosis presenting as chronic coronary syndrome (stable CAD) six months DAPT is generally recommended, though if bleeding risk is high this can be shortened to three months or even one month, particularly if a drugcoated balloon strategy is chosen.

Paclitaxel-coated balloons versus sirolimus-coated balloons

Most DCBs in clinical use are coated with paclitaxel as the antiproliferative drug. However, paclitaxel-coated balloons have recently faced safety concerns. In particular, a meta-analysis5 suggested an increased mortality signal at late follow-up in patients who underwent lower limb intervention with paclitaxel-coated devices (balloons or stents) compared with control therapy (plain balloon angioplasty or bare metal stent implantation) in the context of peripheral vascular disease. However, a meta-analysis focused specifically on coronary intervention showed no significant difference in mortality after paclitaxel-coated balloon angioplasty compared with control devices (plain balloon angioplasty, bare metal stents or DES) at one or two years.6 In fact, at three years, all-cause mortality was significantly

Volume 7 | Issue 4 | 2021 | Cardiology 48

(A) (B) (C) (F) (E) (D)

FIGURE 1: Diagnosis and treatment in a case of in-stent restenosis. (A) Findings at coronary angiography in a patient presenting with symptomatic restenosis in the right coronary artery; (B) high-resolution intravascular imaging with OCT shows heterogeneous tissue type consistent with neoatherosclerosis within the stent; (C) the patient was treated with high-pressure balloon dilation after stenosis; (D) followed by angioplasty with drug-coated balloon with a 60-second dilation; (E) the acute result was excellent at angiography and (F) OCT

lower in the DCB group when compared with control treatment (RR 0.73, 95% CI 0.53 to 1.00; p=0.047). Devices eluting sirolimus have been suggested for some time to have more favourable efficacy and safety profiles compared with paclitaxelcoated devices. Several sirolimus balloons have shown promise in the treatment of restenosis. We recently commenced enrolment in a clinical trial with one particular balloon coated with biolimus-A9.

REFORM trial

The biolimus A9™(BA9™) Drug Coated Balloon (DCB) Study (REFORM, NCT04079192) is a first-in-man study. It is a prospective, randomised, non-inferiority trial to determine the safety and efficacy of the BA9™ DCB in treatment of in-stent restenosis. The study hypothesis is that the BA9™ DCB is non-inferior to a widely available paclitaxel-coated balloon. The primary outcome is a measure of per cent diameter stenosis identified by angiography at six months.

Conclusion

In-stent restenosis may impact up to 5 per cent of patients at one year and one-in-five by 10 years. Restenosis is a multifactorial process driven by stent characteristics

such as stent under-expansion and loss of mechanical integrity. Biological phenomena such as neointimal hyperplasia and neoatherosclerosis are also driving factors. Angioplasty with DCB therapy is an important treatment option in patients with restenosis. To-date, most commercially available devices have used paclitaxel as the active drug. However, sirolimusanalogue-coated devices offer potentially enhanced efficacy and safety profiles and are undergoing testing in dedicated clinical trials.

References

1. Byrne RA, Stone GW, Ormiston J, and Kastrati A. Coronary balloon angioplasty, stents, and scaffolds. The Lancet 390, 781-792, doi:10.1016/s01406736(17)31927-x (2017)

2. Byrne, RA et al. Report of a European Society of Cardiology – European Association of Percutaneous Cardiovascular Interventions taskforce on the evaluation of coronary stents in Europe: Executive summary. Eur Heart J 36, 2608-2620, doi:10.1093/eurheartj/ehv203 (2015)

3. Stefanini GG, et al. Management of myocardial revascularisation failure: an expert consensus document of the EAPCI. EuroIntervention 16, e875-e890, doi:10.4244/EIJ-D-20-00487 (2020)

4. Giacoppo D, et al. Paclitaxel-coated balloon angioplasty vs drug-eluting stenting

Disclosures

RAB reports research funding to the institution of prior employment from Celonova Biosciences and research or educational funding to the institution of current employment from Abbott Vascular, Biosensors, Biotronik, and Boston Scientific, but has not received personal payments from any pharmaceutical company or device manufacturer. RC reports speakers fees from Medtronic. NB reports no conflicts of interest. n

for the treatment of coronary in-stent restenosis: a comprehensive, collaborative, individual patient data meta-analysis of 10 randomised clinical trials (DAEDALUS study). Eur Heart J 41, 3715-3728, doi:10.1093/eurheartj/ehz594 (2020)

5. Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, and Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: A systematic review and meta-analysis of randomised controlled trials. J Am Heart Assoc 7, e011245, doi:10.1161/ JAHA.118.011245 (2018)

6. Scheller B, et al. Survival after coronary revascularisation with paclitaxel-coated balloons. J Am Coll Cardiol 75, 1017-1028, doi:10.1016/j.jacc.2019.11.065 (2020)

49 Cardiology | Volume 7 | Issue 4 | 2021

(A) (B) (A)

FIGURE 2: Follow-up of patient with surveillance angiography. (A) Re-look angiogram six months following treatment showed sustained and durable result in the treated segment; (B) intravascular imaging with OCT showed excellent vessel healing

Spontaneous coronary artery dissection (SCAD)

AUTHOR: Dr Angie Brown, Consultant Cardiologist, Bon Secours Hospital, Dublin, and Medical Director, Irish Heart Foundation

Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI), occurring much more commonly in women with few or no conventional risk factors. A lack of awareness about this condition among healthcare providers has led to under-diagnosis in this relatively younger patient population.

SCAD is defined as a spontaneous separation of the coronary artery wall by intramural haemorrhage that is not iatrogenic, not related to trauma and not due to atherosclerotic coronary artery disease. The true incidence and prevalence of SCAD in the general population is unknown because of under-diagnosis of this condition. Previous reports of SCAD prevalence on coronary angiography of 0.2-1.1 per cent are probably underestimates. In a Japanese series of 326 ACS patients who underwent routine optical coherence tomography (OCT) imaging, SCAD was diagnosed in 4 per cent of cases, as some of these were likely atherosclerotic disease it is likely the prevalence is between 1.7-4 per cent. However, in young women presenting with ACS the prevalence of SCAD is much higher.

Pathology

Arterial dissection with SCAD can occur within or between any of the three layers (intima, media, or adventitia) of the coronary artery wall. Two potential mechanisms for the initiation of arterial wall separation have been proposed. The first is the intimal tear hypothesis, in which a primary disruption in the intimal-luminal interface creates an entry point for intramural haematoma (IMH) accumulation inside the false lumen, leading to separation of the arterial wall. The second hypothesis suggests a haemorrhage into the arterial wall is the primary mechanism, perhaps due

to spontaneous rupture from the vasa vasorum. SCAD results in the accumulation of blood within the false lumen, which can compress the true lumen to varying degrees, compromising antegrade blood flow and causing MI or ischaemia.

In the past it was thought that pregnancy accounted for a significant proportion of SCAD but in contemporary series, pregnancy-related SCAD accounted for <5 per cent of SCAD cases. Pregnancyrelated SCAD can occur antepartum, early post-partum (within six weeks of delivery), late post-partum (six weeks to 12 months), and very late post-partum (12 to 24 months). High progesterone levels during pregnancy can weaken arterial media through alteration of the elastic fibre and mucopolysaccharide content, and impairment of collagen synthesis. Oestrogen may also create a hypercoagulable state. Together these factors were believed to increase the risk of SCAD and thrombosis.

The underlying aetiology of SCAD appears to be multifactorial. There is often an associated underlying predisposing arteriopathy, which may be compounded by a precipitating stressor, culminating in the phenotypic expression of SCAD. Many potential predisposing non-atherosclerotic arteriopathies for SCAD have been reported. The most dominant association reported is fibromuscular dysplasia (FMD) with an observed prevalence varying between 52to-86 per cent in screened SCAD patients. The presence of FMD can weaken artery structure, which is characterised by dysplasia and disorganisation and/ or destruction of smooth muscle cells, fibroblasts, and the connective tissue matrix, affecting any of the three arterial layers and elastic lamina. FMD-affected arteries are prone to dissection and aneurysm formation.

Haemodynamic changes during late pregnancy can also predispose to SCAD. The augmented cardiac output and high circulatory volume during pregnancy can increase shear stress, in the aorta, which can extend to the coronary arteries. The increased intraabdominal pressures during labour can also increase arterial shear stress. Together, these haemodynamic stresses can precipitate pregnancy-related SCAD when superimposed upon arterial architectural changes related to pregnancy or other predisposing aetiologies (eg, FMD). There has been an observation of a potential association between breastfeeding with late and very late post-partum pregnancyrelated SCAD, suggesting that hormonal changes with lactation may compound the effects of pregnancy. Multiparous (or even multigravida) women are believed to be at higher risk for SCAD. Long-term exposure to hormonal therapy – exogenous oestrogen or progesterone may cause similar changes in coronary arterial architecture, and may be a risk factor for

Volume 7 | Issue 4 | 2021 | Cardiology 50

SCAD results in the accumulation of blood within the false lumen, which can compress the true lumen to varying degrees, compromising antegrade blood flow and causing MI or ischaemia

SCAD. Hormone replacement therapy (HRT) is also associated with higher recurrent MI on follow-up compared with those not on HRT.

Several chronic systemic inflammatory conditions such as systemic lupus erythematosus (SLE), giant cell arteritis, polyarteritis nodosa (PAN), ulcerative colitis, Crohn’s disease, sarcoidosis, Wegener granulomatosis, or rheumatoid arthritis (RA) have been noted in SCAD case reports. However, the incidence of acute inflammation associated with SCAD is very low. A possible link between systemic inflammation and SCAD is suspected to be due to chronic inflammation from vasculitis

Several connective tissue disorders have also been associated with SCAD, most notably Marfan syndrome and EhlersDanlos type 4 syndromes. However, the reported frequency of these and other associated connective tissue conditions is infrequent. Thus, although many of these disorders can be identified on genetic screening, the yield is low unless patients have clear clinical characteristics suggestive of these disorders.

Precipitating factors

Stressors that result in an increase in arterial shear stress can trigger SCAD, especially in patients with underlying predisposing arteriopathies.

These include physical activities (especially isometric exercises), hormonal therapy, recreational drugs such as cocaine and amphetamines and intense Valsalva-like activities (eg, childbirth, coughing, retching, vomiting, bowel movement). Intense emotional stress may have a different pathophysiological trigger, probably related to stress catecholamines. This may increase myocardial contractility or vasospasm, which can increase arterial shear stress.

Acute exposures to high-dose hormonal therapy (eg, injections of beta-human chorionic gonadotropin, corticosteroids) have also been implicated as triggers for

SCAD, potentially through accelerated arterial architectural disruption or haemodynamic stress such as acute hypertension.

Men and women have different prevalence of predisposing and precipitating factors. In a recent paper, men were more likely to report isometric exercises, but were less likely to report emotional stressors compared with women. These findings highlight potential lifestyle changes that may affect recurrent SCAD risk.

Presentation

Most patients complain of chest pain or pain radiation to the arms or neck, nausea or vomiting, diaphoresis, dyspnoea, and back pain. They also have a spectrum of clinical presentations, from acute conorary syndrome (ACS) to full STEMI. A small proportion can be complicated with ventricular arrhythmias, cardiogenic shock, or sudden cardiac death. Patients often present to hospital later with a further delay in investigation for patients with non-STEMI.

Diagnosis

The history, abnormal ECG and raised troponin underlies the diagnosis of ACS or STEMI. Coronary angiography is widely available and is the first-line imaging for patients presenting with ACS. However, coronary angiography has significant limitations in diagnosing SCAD because it does not image the arterial wall. Dedicated intracoronary imaging (OCT and intravascular ultrasound (IVUS)) that images the arterial wall layers improves SCAD diagnosis, but it is not as widely available and is associated with additional risks and costs. Thus, coronary angiography remains the primary diagnostic tool in SCAD diagnosis, so it is crucial that angiographers understand the angiographic variants of SCAD.

The conventional angiographic description of SCAD includes the appearance of extraluminal contrast staining, multiple radiolucent lumens, spiral dissection, and intraluminal filling

defects. However, the predominant angiographic appearance of SCAD consists of smooth narrowing of varying severity and length due to IMH. Thus, a SCAD angiographic classification was devised:

 Type 1 describes the appearance of arterial wall contrast staining with multiple radiolucent lumens.

 Type 2 describes diffuse stenosis of varying severity and length (typically >20mm) and with normal proximal and distal segments (type 2A variant), or it may be a diffuses stenosis that extends to the apical tip of the artery (type 2B variant).

 Type 3 describes focal or tubular (typically <20mm) stenosis that mimics atherosclerosis, which therefore requires intracoronary imaging to confirm the diagnosis.

Using this classification, the most common SCAD angiographic appearance is type 2 with the least common being type 3.

The type 2B variant may be mistaken as ‘normal vessel tapering’, but there is usually a discernible demarcation from a normal vessel to stenosis. Furthermore, there is usually a corresponding regional wall motion abnormality on ventriculography. The type 3 variant may be significantly underdiagnosed and may be mistaken for atherosclerotic disease.

The LAD and its branches are most commonly affected in the mid and distal vessel, multiple arteries are rarely involved.

As part of the investigation of SCAD, it has become routine practice in several centres to screen for predisposing arteriopathies associated with SCAD. Because of the strong association with FMD, the renal and iliac arteries should be imaged for FMD during coronary angiography with nonselective abdominal and iliac aortograms if SCAD is suspected. Alternatively, non-invasive CTA FMD screening may be performed, though the sensitivity of diagnosing FMD is much lower than

51 Cardiology | Volume 7 | Issue 4 | 2021

that with invasive angiography. CTA of the head and neck should be considered to assess for cerebrovascular FMD and intracranial aneurysm which is associated.

Both OCT and IVUS provide complementary information helping diagnose SCAD. OCT has a superior spatial resolution versus IVUS, with lower resolution, but better penetration. For SCAD imaging, OCT is superior for visualising intimal tears, intraluminal thrombi, false lumens, and IMH, but it is limited by optical penetration, and may not depict the entire depth of the IMH. IVUS has adequate resolution to visualise IMH and false lumens, but the lumen-intimal interface is not as clearly delineated. IVUS does provide deeper vessel visualisation, allowing better appreciation of the extent of IMH. Overall, OCT is preferred for imaging SCAD due to its superiority in visualising IMH, intimal disruption, and double lumens, especially because there is no clinical need to evaluate the full depth and extent of IMH. Moreover, OCT is also good at visualising stent strut apposition, thus allowing stent optimisation if intervention is pursued. However, there are potential risks with intracoronary imaging in the setting of SCAD, including the risks of extending dissection with the wire or imaging catheter, hydraulic extension with OCT contrast injection, catheter-induced occlusion, and guide catheter iatrogenic dissection. Thus, great care must be taken when performing intracoronary imaging.

Cardiac CTA has much lower spatial resolution compared with conventional angiography and has challenges in evaluating the lumens and walls of small coronary arteries (especially those <2.5 mm diameter). Because most of SCAD affects non-proximal arteries and does not have extraluminal contrast staining, cardiac CTA has limited capacity to diagnose SCAD.

Management

A detailed history to assess for potential underlying connective tissue disorders,

systemic inflammatory disease, pregnancy history, hormonal therapy, and precipitating factors should be obtained. In terms of genetic screening, the yield for connective tissue disorders with routine genetic testing is very low. In addition, familial inheritance of SCAD was only identified in a small minority of cases. Further studies that evaluate the genetic predispositions are needed, but because of the low yield routine genetic screening is not currently recommended. Likewise, blood work to screen for inflammatory disease is of low yield and is not routinely performed unless indicated in the history.

As there are no randomised trials comparing medical therapy or revascularisation strategies in SCAD, recommendations on management are predominantly on the basis of expert opinion from observational series. Beta blockers reduce arterial shear stress and are used in aortic dissection so are also recommended in SCAD for the same reason and may potentially have beneficial effects on reducing the risk of malignant arrhythmias.

As aspirin use in ACS and secondary prevention is effective and has a low sideeffect profile, aspirin is reasonable to use for acute and long-term SCAD management.

Clopidogrel for acute management of SCAD patients not treated with stents is of uncertain benefit. However, as a proportion of SCAD involves intimal tears, which can be prothrombotic, dual antiplatelet therapy (DAPT) could be empirically beneficial. Reducing the false lumen thrombus burden with DAPT can also theoretically reduce true lumen compression. Therefore, clopidogrel is often administered for one-to-12 months post-SCAD, and then it is typically discontinued if there is no further ischaemic pain or if angiographic healing is subsequently demonstrated, although there is no supportive evidence for this approach. There is no data on the use of novel P2Y12 antagonists (ticagrelor and prasugrel) for SCAD management. Glycoprotein IIb/IIIa inhibitors have also

not been evaluated for SCAD and are not recommended because of their higher bleeding risk, and a potential risk of extending the dissection.

Heparin is routinely administered for ACS management in hospital, but the clinical benefit has not been established for SCAD. There is a potential risk of extending the dissection with anticoagulation, which is balanced by the potential benefit of resolving overlying thrombus and improving true lumen patency. Heparin should likely be discontinued once the SCAD diagnosis is made. Thrombolytic therapy should be avoided in SCAD because there have been some case reports of harm and clinical deterioration due to extension of IMH and dissection.

Angiotensin converting enzyme (ACE)/AII inhibitors tend to only be administered to SCAD patients with significant left ventricular dysfunction or for treatment of hypertension.

Nitrates or calcium channel blockers may be used if there is an element of coronary artery spasm.

Because of the uncertainty of any benefit and the general lack of atherosclerosis in SCAD patients, statins tend to only be administered to patients with pre-existing dyslipidaemia.

Overall a conservative approach is preferred as SCAD arteries heal spontaneously in most cases, and revascularisation is associated with high failure rates. In prospective series in which repeat coronary angiograms were performed, spontaneous angiographic healing was observed in most of the cases with conservative management. Healing has been shown to occur at around 26 days post-dissection in some with a small proportion of cases with residual dissections at late follow-up.

Although conservative therapy is usually recommended, a small proportion of patients need to be considered for

Volume 7 | Issue 4 | 2021 | Cardiology 52

revascularisation, including those with a major vessel occlusion, ongoing or recurrent ischaemia, haemodynamic instability, ventricular arrhythmias, or left main dissection. Percutaneous coronary intervention (PCI) is performed if the anatomy is suitable; otherwise, coronary artery bypass grafting (CABG) should be considered. As patients treated conservatively may become unstable and require intervention, inpatient monitoring is recommended for several days.

Several series have reported poor technical success with PCI for SCAD with high rates of extension of dissections during PCI, more frequent urgent CABG, and higher stent thrombosis. Patients treated conservatively seem to have lower inhospital major cardiac adverse events (MACEs) compared with those treated with revascularisation.

These suboptimal results are a consequence of multiple challenges with PCI with this pathology. These arteries are weakened by the underlying arteriopathies, and are prone to iatrogenic dissections and extension of dissections during PCI. It may be challenging to enter the true lumen with the coronary guidewire, especially in the presence of type 1 angiographic SCAD with intimal disruption. With wiring, angioplasty, or stenting, the IMH can often propagate anterogradely or retrogradely, further compromising the true lumen and extending the dissection. Long stents are typically required because dissections are extensive, with a higher risk of restenosis. Furthermore, SCAD often involves distal coronary segments that are too small for stents. Moreover, with the natural resorption of IMH over time, there may be subacute and late strut malapposition, which can increase the risk of stent thrombosis.

Emergency CABG is considered for patients with left main dissections, extensive dissections involving proximal arteries, or in patients in whom PCI failed or who are anatomically unsuitable for PCI. Small observational studies show good acute survival following CABG. However,

long-term results with CABG appear suboptimal, with reported graft patency of 27 per cent in a small series, which may be related to spontaneous arterial healing, with subsequent competitive flow causing graft thrombosis. Nevertheless, CABG is an important temporising strategy, providing coronary blood flow and myocardial perfusion for these critically ill patients in whom PCI is unsuitable.

Cardiovascular outcomes

The in-hospital outcomes of SCAD patients are reasonably good in contemporary prospective series. Acute in-hospital mortality was <5 per cent in modern series, and in-hospital recurrent MI, need for urgent revascularisation in conservatively managed patients, or other MACEs were 5-to-10 per cent. However, following hospital discharge, a significant proportion of patients can have recurrent chest pains and MACEs. Subacute MACEs were reported in 10-to-20 per cent of patients at two-year follow-up, with recurrent SCAD occurring in ∼15 per cent. Longer-term recurrent SCAD rates at four to five years were reported at ∼27 per cent. Overall longterm survival is good in this cohort (>95 per cent), but as long-term MACE rates can be high it is important that patients are followed up closely.

Post-discharge recommendations

Ongoing medical management usually consists of aspirin and beta-blockers, with the addition of ACE inhibitors with optimal treatment of hypertension and statins as required. Cardiac rehabilitation is important; ideally a dedicated programme inclusive of exercise rehabilitation with initial low-level targets for heart rates and blood pressure and light resistance training, psychosocial counselling, and peer group support. SCAD patients may be particularly at risk of post-traumatic stress disorder (PTSD) and other adverse psychological issues as SCAD affects a younger, lowrisk population where a life-threatening condition is unexpected. Post-pregnancy SCAD patients have the added challenge of a new baby. Cardiac rehab has been shown

to be helpful and in some cases with counselling, cognitive behaviour therapy (CBT), stress-reducing therapies or medication for anxiety or depression as appropriate.

In terms of hormonal therapy, continued use should generally be avoided, because of the higher risk of recurrent MI. Among women of childbearing age, future pregnancy should also likely be avoided because of the potential risk of recurrent SCAD. Patients should try to reduce potential triggers such as emotional stress and heavy weight lifting, etc.

Conclusion

SCAD is an infrequent cause of ACS, but is not as rare as previously thought, with the true prevalence unknown but accounting for a higher percentage of ACS in younger women presenting with MI. It is frequently associated with predisposing and precipitating factors, such as FMD, and isometric and emotional stresses. It should be on the differential diagnosis of young to middle-aged women presenting with MI. Conservative therapy is favoured, except for patients with unstable symptoms, haemodynamic instability, or left main dissection. Acute survival is good; however, long-term MACEs are frequent, including recurrent SCAD. Thus, SCAD patients should be closely followed for cardiac events, with further prospective studies exploring strategies to improve cardiovascular outcomes needed. n

References on request

For SCAD patient support contact the Irish Heart Foundation Nurse support line, tel 01 6685001 or email support@irishheart.ie . Online support also available for patients and their families via the IHF Heart Support Network Private Facebook Page.

53 Cardiology | Volume 7 | Issue 4 | 2021

Sláintecare Galway University Hospital Community Cardiac Diagnostics Service

In recent years in Irish healthcare, there has been focus on shifting more care into the community, closer to patients’ homes. This is reinforced in the Sláintecare Report and the intended approach is embodied by the ‘right care, right place, right time’ mantra.

There has long been recognition of the difficulty that GPs have in accessing diagnostics. A report from the ICGP demonstrated that:

 <20 per cent of GPs have direct access to echocardiography;

 <25 per cent of GPs have direct access to heart monitoring (eg, Holter/R-test);

 86.7 per cent of GPs agree or strongly agree that improved access to diagnostics would reduce their referrals to emergency departments (EDs).

Indeed, one of the effects of this lack of access to diagnostics is that GPs often have little option but to refer to outpatient clinics, with long wait times, or acute services such as the ED or Acute Medical Units. Direct access for GPs to diagnostics addresses these needs and meets the Sláintecare vision of shifting care appropriately, away from a hospitalcentric model.

Mobile diagnostics is not a new, indeed in October 1914 the first ‘petite Curie’, brought x-rays to the frontlines of World War I (Figure 1). Community cardiac diagnostics have been running in the UK for a significant period, with a positive impact for patients. It is reported that they prefer attending less stressful and more accessible clinics, and patient-reported experience measures are compelling. A similar communitybased cardiac diagnostics service in Sligo demonstrated a saving of 250 bed days over a six-week period, by facilitating early discharge from hospital with follow-up diagnostics being delivered in the community.

Sláintecare Integration Fund

In 2019, all healthcare staff and organisations were invited to submit ideas to Sláintecare to access some of a €20 million Integration Fund. There was a particular emphasis on initiatives that would support the shift to community-based care and help to reduce and prevent hospital visits. The cardiology department in Galway University Hospital was successful in its application and received Sláintecare funding to commence its Community Cardiac Diagnostics Programme. This funding allowed us to purchase a portable echocardiography machine, of an equivalent standard to the hospital-based machine and 10 heart (R-test) monitors. It also covered the salary of a senior cardiac physiologist, who performs and reports the echocardiograms, and an administrative post.

The service currently operates from five clinics in Tuam, Claremorris, Gort, and two in Galway city. These sites are

reachable by staff within 45 minutes, thus maximising the number of diagnostic slots available. The service is currently providing direct access for GPs to 40 diagnostic slots per week.

The service is provided by the team of cardiac physiologists, under the clinical support of the consultant cardiologists from Galway University Hospital, rotating out to the centres. The cardiac physiologists providing the service have internationally recognised accreditation in echocardiography. This combined with it being under the clinical governance of the hospital gives associated quality assurance. The clinical support and governance of the consultant cardiologists is vital, in terms of their expertise for more difficult cases and continuity of care in referral pathways.

All images and reports of investigations performed are archived to the hospital’s

Volume 7 | Issue 4 | 2021 | Cardiology 54

AUTHOR: Paul Nolan, Chief II Cardiac Physiologist, Associate Academic Officer, Cardiac Investigations, Saolta University Health Care Group, University Hospital Galway FIGURE 1: A ‘petite Curie’, mobile x-ray vehicle from WWI

cardiovascular IT systems and uploaded to the hospital’s electronic chart. This ensures continuity of care in the case of referral to the hospital at a future date. It also ensures that tests are not repeated unnecessarily.

One of the initiatives the cardiology team worked on was to create a GP summary template for various findings. The aim of these was to translate what can be quite a technical echocardiogram report into a summary with clear guideline-driven recommendations; for example, in cases of mild aortic stenosis, with no calcification, we recommend to repeat the Echo in twoto-three years. The aim of this is to make it easier for GPs to manage the patient and their results. In the case of significant findings requiring more urgent referral, our cardiology team will arrange this with the GP advised of this.

Indications

Typical indications for echocardiography from primary care would include:

 Murmur

l Symptomatic murmur.

l Asymptomatic murmur with other signs suggestive of structural heart disease.

 Suspected heart failure

l Clinical signs of heart failure.

l Unexplained shortness of breath if ECG/CXR abnormal.

l With higher priority given to referrals with elevated BNP.

 Syncope

l With clinical suspicion of cardiac disease.

l Exertional syncope.

l New onset, rate controlled, atrial fibrillation.

l Palpitations.

The R-test monitor records a full heart rate trend and automatically records

arrhythmias, including everything from ventricular ectopic to atrial fibrillation and ventricular tachycardia. Indications for R-test (similar to Holter) include:

 Syncope and presyncope, where it is unlikely to be vasovagal.

 Palpitations

l Symptomatic and unlikely to be ectopic beats.

Palpitations can be a troublesome diagnostic challenge and can cover everything from a patient being very aware of their heartbeat, to ectopic beats, to a significant arrhythmia. While a normal resting 12-lead ECG gives some degree of reassurance, the diagnosis is made by getting a symptom/rhythm correlation. It has been shown that 24to-48 hour ambulatory monitoring has a relatively low diagnostic yield unless the patient has daily palpitations and whilst event monitors have a higher diagnostic yield, they are typically only fitted for a couple of weeks. New technology, such as hand-held ECGs, for example, the Alivecor device, have a high yield for a relatively low, once-off cost.

In the setting of palpitations, a normal echocardiogram can be reassuring. Where the nature of the palpitations has not yet been characterised, a normal Echo and a normal ECG would suggest no further management is required. If the palpitations were very frequent or distressing, referral could be considered. 5

Some signs, which would point to an increased likelihood of a significant arrhythmia, include:

 Symptoms at work;

 Exertional symptoms;

 Symptoms disturbing sleep;

 Known cardiovascular disease;

 Older age;

 On cardiovascular medication.

Service to-date

The Sláintecare GUH Community

Cardiac Diagnostic Clinic has seen over 290 patient in the first two months of 2021, performing 216 echocardiograms

55 Cardiology | Volume 7 | Issue 4 | 2021

FIGURE 2: GUH Community Cardiac Diagnostics Programme data to-date

New technology, such as hand-held ECGs, for example, the Alivecor device, have a high yield for a relatively low, once-off cost

and 75 R-test monitors (Figure 2). A total 87 per cent of tests were completed within six weeks of referral and over half were seen in two weeks or less.

Over a quarter (28 per cent) of tests have a significant abnormality that would require follow-up but in 59 per cent of these cases, the follow-up could be left with the GP, furnished with a recommendation in the diagnostic report.

Significant findings that required onward referral by the service directly included:

 Reduced left ventricular function;

 Significant valve disease;

 Severe pulmonary hypertension;

 Newly discovered paroxysmal atrial fibrillation.

Future direction

The service has been widely adopted by GPs with high levels of satisfaction from patients. It is leading to more timely diagnosis as outlined in the associated case study. One 85-year-old patient who attended our Gort clinic sums up the improved patient experience. She is reliant on taxis to take her to hospital appointments, which is an over 90km round trip and a taxi fare of €110. The ability to attend our community clinic transformed this to a five-minute trip.

With such benefits in terms of wait times, earlier diagnosis, and improved patient experience – we are hopeful that funding for the service will be continued and perhaps expanded as community-based integrated care hubs are rolled out nationally.

This service is dependent on the support of the primary care centres, Community Health Organisations, Galway University Hospital management and the Saolta Project Management Office. The key element is the hard work and support of the team of cardiac physiologists, cardiac consultants and cardiology administration staff in Galway University Hospital. n

CASE STUDY

An 83-year-old woman was recently seen by her GP, and although she had no concerning cardiovascular symptoms, the GP noted an ejection systolic murmur. This lady had previously had an Echo which showed aortic sclerosis and recommended repeat echo in five years. Given the presence of the murmur and the previous Echo, the patient was referred for echocardiography.

Her referral was received via Healthlink on January 28 and this was performed in our Tuam clinic on February 28 and revealed severe aortic stenosis. Echocardiography can classify the severity of valve narrowing by measuring the pressure gradient across the valve and through a combination of measurements estimate the aortic valve area (AVA). Severe aortic stenosis is classified as:

 Peak velocity across the valve of >4.0m/s – the narrower the valve, the faster the blood flow;

 Mean pressure gradient of >40mmHg;

 Estimated aortic valve area of <1.0cm2 –normal area is 2-4cm2

The patient was referred to our structural heart clinic. There is ample evidence that in patients with symptomatic severe aortic stenosis that valve replacement improves survival, symptoms and overall cardiac function.

There are two intervention options for patients with severe aortic stenosis –surgical valve replacement (SAVR) or transcatheter aortic valve replacement

References

1. Committee on the Future of Healthcare, Sláintecare Report.

May 2017

2. Access to diagnostics: A key enabler for a primary care led health service.

ICGP 2013

3. All wales community cardiology evaluation. Formative evaluation report for British Heart Foundation and All Wales Cardiac Network. March 2018

4. Bringing cardiac diagnostics to the

(TAVI), where the valve is delivered via a catheter from the femoral artery in a non-surgical approach. Current guidelines support the use of TAVI in patients who are either too high risk or high risk for SAVR. In patients with lower surgical risk, decisions are made based on issues such as valve durability, procedural difficulty, co-morbidities and patient preference. The overall recommendation is made by a multidisciplinary heart team, including cardiologists and cardiac surgeons.

These guidelines, based on the evidence that asymptomatic patients with severe AS and preserved ejection fraction have a similar survival to age matched cohorts, also recommend following up these patients at six-monthly intervals, with prompt intervention at the onset of symptoms such as shortness of breath, reduced exercise tolerance, pre-syncope or syncope, or a reduction in ejection fraction.

When the patient was seen in the clinic, her functional status was unclear. As aortic stenosis is a degenerative valvular disease, a patient’s functional capacity can decline gradually, unnoticed by the patient. She had an exercise test performed to quantify her exercise capacity and this was reassuring and will be followed up in the structural heart clinic in six months’ time with a repeat echocardiogram.

Via the new Sláintecare Galway University Hospital Cardiac Diagnostics Service, the patient was diagnosed, seen in a specialist clinic and managed within 10 weeks from referral.

heart of the community. International Journal of Integrated Care. 2017

5. Approach to palpitations. Australian Journal for General Practitioners . The Royal Australian College of General Practitioners (RACGP). 2019

6. 10 steps before your refer for palpitations. Br J Cardiol. 2009

7. 2020 ACC/AHA Guideline for the management of patients with valvular heart disease. Circulation. 2021

Volume 7 | Issue 4 | 2021 | Cardiology 56

Latest module

Cardiac amyloidosis- Overview, Diagnosis and Management

Learning objectives of this module:

l Understand the principal causes (AL amyloidosis and ATTR) and underlying pathophysiology of cardiac amyloidosis

l Identify patients to screen for cardiac amyloidosis and the subsequent diagnostic process

l Develop insight into the management of cardiac amyloidosis and its underlying causes

Successful completion of this module will earn you 2 CPD credits visit www.medilearning.ie/doctorcpd.

A B C

doctorCPD.ie

Free CPD – now accessible on android, iPhone and tablet