ISSUE @ A GLANCE
European Heart Journal (2017) 38, 2081–2085 doi:10.1093/eurheartj/ehx384
Management of arrhythmias: NOACs, digoxin, alcohol, light, and devices Thomas F. Lu¨scher, MD, FESC Editor-in-Chief, Zurich Heart House, Careum Campus, Moussonstrasse 4, 8091 Zurich, Switzerland
Atrial fibrillation has taken centre stage in cardiovascular medicine with the ageing population and the introduction of novel treatment options such as catheter-based ablation1,2 and, more recently, nonvitamin K oral anticoagulants or NOACs.3,4 In a Special Article entitled ‘Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary’, Hein Heidbuchel and colleagues present on behalf of the European Heart Rhythm Association their novel guide.5 Since 2013, when the last version was published, numerous new studies have appeared that are relevant for patient management, as also outlined in the 2016 ESC Guidelines.6 The current practical guide includes new information, in particular an updated discussion on the definition of ‘non-valvular atrial fibrillation’ and the eligibility for NOACs including novel agents such as edoxaban.7 Furthermore, the 2017 practical guide contains tailored dosing information, an expanded chapter on neurological scenarios such as ischaemic stroke or intracranial haemorrhage during NOAC therapy, an updated anticoagulation card, and more specifics on start-up and follow-up issues. Many antiarrythmic drugs have been abandoned or their indication markedly restricted, mainly due to proarrhythmic or other side effects. The oldest antiarrythmic is digoxin, initially described by William Withering in 1778 after he had learned of the use of the plant in treating ‘dropsy’ or oedema—we would call it congestive heart failure today—from mother Hutton, an old woman who practised as a folk herbalist in Shropshire.8 Although in use for more than two centuries, its efficacy and safety are still debated in spite of numerous trials with the drug.9 This issue is discussed by Udo Bavendiek and colleagues from the Hannover Medical School in Germany in a Current Opinion entitled ‘Assumption vs. evidence: the case of digoxin in atrial fibrillation and heart failure’.10 The numerous publications on digitalis caused increasing uncertainty in the medical and patient community regarding the start or continuation of such a treatment in patients with atrial fibrillation and/or heart failure. Even though these publications all end in mandating the conduct of further randomized trials, they increase the difficulties in the conduct of
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
proper studies which have been initiated, such as RATE-AF and DIGIT-HF. These trials should be able to answer the question of whether treatment with cardiac glycosides is beneficial or not. In the present review article, the authors try to clarify uncertainties based on current evidence and emphasize the need of further prospective clinical trials. Among many, alcohol consumption is a risk factor for cardiac arrhythmias. Retrospective analyses suggest that supraventricular arrhythmias can occur after excessive acute alcohol consumption, but prospective data are limited. Acute excessive alcohol consumption usually occurs during parties and celebrations. Stefan Brunner and colleagues from the Ludwig Maximillian University in Munich in Germany report the results of their prospective investigation on alcohol-induced arrhythmias at the Octoberfest in 2015 in a research article ‘Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich Octoberfest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW)’.11 They enrolled 3028 voluntary participants with a mean age of 34 years who received a smartphone-based ECG and breath alcohol concentration measurements. Similarly, they analysed 4131 participants of the community-based KORA S4 study and associated cardiac arrhythmias with chronic alcohol consumption. During the Octoberfest, mean breath alcohol concentration was 0.85 ± 0.54 g/kg. Cardiac arrhythmias such as sinus tachycardia and other arrhythmia subtypes occurred in 31% (Figure 1). Breath alcohol concentration was significantly associated with cardiac arrhythmias overall, with an odds ratio per 1 unit change of 1.75, and sinus tachycardia in particular with an odds ratio per 1 unit change of 1.96. Respiratory sinus arrhythmia as a measure of autonomic tone was significantly reduced under the influence of alcohol. In KORA S4, chronic alcohol consumption was associated with sinus tachycardia with an odds ratio of 1.03. Thus, acute alcohol consumption is indeed associated with cardiac arrhythmias and sinus tachycardia, in particular as a reflection of autonomic imbalance as assessed by significantly reduced respiratory sinus arrhythmia. Such an imbalance might lead to sympathetically triggered atrial fibrillation resembling the holiday
With thanks to Amelia Meier-Batschelet for help with compilation of this article. C The Author 2017. For permissions, please email: [email protected]. Published on behalf of the European Society of Cardiology. All rights reserved. V
2082
Issue @ a Glance
E
Primary outcome of any arrhythmia 50.0 Chi-square test for trend: p0.79 to ≤1.20 >1.20 >0.44 to ≤0.79 Quarles of Breath Alcohol Concentraon (g/kg)
27.9
30.0
10.0
0.0
46.6
35.0
15.0
5.0
Chi-square tesor trend: p0.44 to ≤0.79 >0.79 to ≤1.20 >1.20 Quarles of Breath Alcohol Concentraon (g/kg)
Figure 1 Examples and Prevalence of Cardiac Arrhythmias. A–E. Representative ECG recordings obtained in our acute alcohol cohort. ECG recordings show sinus rhythm (A), sinus tachycardia (B), premature atrial complex (C), premature ventricular complex (D), atrial fibrillation (E). F–G. Clustered bars represent the prevalence of the primary outcome of any cardiac arrhythmia (F) and sinus tachycardia (G) in our acute alcohol cohort by quartiles of BAC. Within each cluster, bars represent the overall cohort (green), and sex-stratified results for men (blue) and women (red). Clusters compared by v2 test for trend (from Brunner S, Herbel R, Drobesch C, Peters A, Massberg S, K€a€ab S, Sinner MF. Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich October fest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW). See Pages 2100–2106).
heart syndrome. The provocative findings of this manuscript are put into clinical context in an Editorial by David Conen from the McMaster University in Hamilton, Canada.12 More serious arrhythmias originate from the ventricular cavity and are an important cause of sudden cardiac death. Patients after myocardial infarction are particularly at risk of such arrhythmias. However, although preventive measures are at hand with modern implantable cardioverter defibrillators or ICDs,13 prediction of such events remains challenging. In a second research manuscript ‘Prediction of sudden and non-sudden cardiac death in postinfarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy’, Axel Bauer and colleagues from the University Hospital Munich in Germany set out to test the value of periodic repolarization dynamics, a recently validated electrocardiographic marker of sympathetic activity, as predictors of sudden and non-sudden cardiac death and to improve identification of patients that profit from ICD implantation.14 The authors included 856 post-infarction patients with left ventricular ejection fraction
European Heart Journal (2017) 38, 2081–2085 doi:10.1093/eurheartj/ehx384
Management of arrhythmias: NOACs, digoxin, alcohol, light, and devices Thomas F. Lu¨scher, MD, FESC Editor-in-Chief, Zurich Heart House, Careum Campus, Moussonstrasse 4, 8091 Zurich, Switzerland
Atrial fibrillation has taken centre stage in cardiovascular medicine with the ageing population and the introduction of novel treatment options such as catheter-based ablation1,2 and, more recently, nonvitamin K oral anticoagulants or NOACs.3,4 In a Special Article entitled ‘Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: executive summary’, Hein Heidbuchel and colleagues present on behalf of the European Heart Rhythm Association their novel guide.5 Since 2013, when the last version was published, numerous new studies have appeared that are relevant for patient management, as also outlined in the 2016 ESC Guidelines.6 The current practical guide includes new information, in particular an updated discussion on the definition of ‘non-valvular atrial fibrillation’ and the eligibility for NOACs including novel agents such as edoxaban.7 Furthermore, the 2017 practical guide contains tailored dosing information, an expanded chapter on neurological scenarios such as ischaemic stroke or intracranial haemorrhage during NOAC therapy, an updated anticoagulation card, and more specifics on start-up and follow-up issues. Many antiarrythmic drugs have been abandoned or their indication markedly restricted, mainly due to proarrhythmic or other side effects. The oldest antiarrythmic is digoxin, initially described by William Withering in 1778 after he had learned of the use of the plant in treating ‘dropsy’ or oedema—we would call it congestive heart failure today—from mother Hutton, an old woman who practised as a folk herbalist in Shropshire.8 Although in use for more than two centuries, its efficacy and safety are still debated in spite of numerous trials with the drug.9 This issue is discussed by Udo Bavendiek and colleagues from the Hannover Medical School in Germany in a Current Opinion entitled ‘Assumption vs. evidence: the case of digoxin in atrial fibrillation and heart failure’.10 The numerous publications on digitalis caused increasing uncertainty in the medical and patient community regarding the start or continuation of such a treatment in patients with atrial fibrillation and/or heart failure. Even though these publications all end in mandating the conduct of further randomized trials, they increase the difficulties in the conduct of
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .
proper studies which have been initiated, such as RATE-AF and DIGIT-HF. These trials should be able to answer the question of whether treatment with cardiac glycosides is beneficial or not. In the present review article, the authors try to clarify uncertainties based on current evidence and emphasize the need of further prospective clinical trials. Among many, alcohol consumption is a risk factor for cardiac arrhythmias. Retrospective analyses suggest that supraventricular arrhythmias can occur after excessive acute alcohol consumption, but prospective data are limited. Acute excessive alcohol consumption usually occurs during parties and celebrations. Stefan Brunner and colleagues from the Ludwig Maximillian University in Munich in Germany report the results of their prospective investigation on alcohol-induced arrhythmias at the Octoberfest in 2015 in a research article ‘Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich Octoberfest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW)’.11 They enrolled 3028 voluntary participants with a mean age of 34 years who received a smartphone-based ECG and breath alcohol concentration measurements. Similarly, they analysed 4131 participants of the community-based KORA S4 study and associated cardiac arrhythmias with chronic alcohol consumption. During the Octoberfest, mean breath alcohol concentration was 0.85 ± 0.54 g/kg. Cardiac arrhythmias such as sinus tachycardia and other arrhythmia subtypes occurred in 31% (Figure 1). Breath alcohol concentration was significantly associated with cardiac arrhythmias overall, with an odds ratio per 1 unit change of 1.75, and sinus tachycardia in particular with an odds ratio per 1 unit change of 1.96. Respiratory sinus arrhythmia as a measure of autonomic tone was significantly reduced under the influence of alcohol. In KORA S4, chronic alcohol consumption was associated with sinus tachycardia with an odds ratio of 1.03. Thus, acute alcohol consumption is indeed associated with cardiac arrhythmias and sinus tachycardia, in particular as a reflection of autonomic imbalance as assessed by significantly reduced respiratory sinus arrhythmia. Such an imbalance might lead to sympathetically triggered atrial fibrillation resembling the holiday
With thanks to Amelia Meier-Batschelet for help with compilation of this article. C The Author 2017. For permissions, please email: [email protected]. Published on behalf of the European Society of Cardiology. All rights reserved. V
2082
Issue @ a Glance
E
Primary outcome of any arrhythmia 50.0 Chi-square test for trend: p0.79 to ≤1.20 >1.20 >0.44 to ≤0.79 Quarles of Breath Alcohol Concentraon (g/kg)
27.9
30.0
10.0
0.0
46.6
35.0
15.0
5.0
Chi-square tesor trend: p0.44 to ≤0.79 >0.79 to ≤1.20 >1.20 Quarles of Breath Alcohol Concentraon (g/kg)
Figure 1 Examples and Prevalence of Cardiac Arrhythmias. A–E. Representative ECG recordings obtained in our acute alcohol cohort. ECG recordings show sinus rhythm (A), sinus tachycardia (B), premature atrial complex (C), premature ventricular complex (D), atrial fibrillation (E). F–G. Clustered bars represent the prevalence of the primary outcome of any cardiac arrhythmia (F) and sinus tachycardia (G) in our acute alcohol cohort by quartiles of BAC. Within each cluster, bars represent the overall cohort (green), and sex-stratified results for men (blue) and women (red). Clusters compared by v2 test for trend (from Brunner S, Herbel R, Drobesch C, Peters A, Massberg S, K€a€ab S, Sinner MF. Alcohol consumption, sinus tachycardia, and cardiac arrhythmias at the Munich October fest: results from the Munich Beer Related Electrocardiogram Workup Study (MunichBREW). See Pages 2100–2106).
heart syndrome. The provocative findings of this manuscript are put into clinical context in an Editorial by David Conen from the McMaster University in Hamilton, Canada.12 More serious arrhythmias originate from the ventricular cavity and are an important cause of sudden cardiac death. Patients after myocardial infarction are particularly at risk of such arrhythmias. However, although preventive measures are at hand with modern implantable cardioverter defibrillators or ICDs,13 prediction of such events remains challenging. In a second research manuscript ‘Prediction of sudden and non-sudden cardiac death in postinfarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy’, Axel Bauer and colleagues from the University Hospital Munich in Germany set out to test the value of periodic repolarization dynamics, a recently validated electrocardiographic marker of sympathetic activity, as predictors of sudden and non-sudden cardiac death and to improve identification of patients that profit from ICD implantation.14 The authors included 856 post-infarction patients with left ventricular ejection fraction
