The year in arrythmias: real-world data on risk factors, ablation, and genetics

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. Arrhythmias remain an important cause of morbidity and mortality. While ventricular arrhythmias are often life-threatening,1 supraventricular arrhythmias are highy symptomatic and, in the case of atrial fibrillation, are linked to stroke and bad outcomes.2 The most recent developments in prevention both for healthy and sporty individuals3 and those with genetic predisposition4–7 for arrhythmias as well as novel therapeutic strategies and their application8 and effectiveness9–11 are summarized in the ‘The Year in Cardiology 2018: arrhythmias and cardiac devices’ by Jan Steffel from the University Hospital Zurich in Switzerland, and colleagues.12 Age and blood pressure are important risk factors for atrial fibrillation. However, how the actual blood pressure level and the duration of hypertension affect the risk of ischaemic stroke remains to be clarified. In their article entitled ‘Effect of hypertension duration and blood pressure level on ischaemic stroke risk in atrial fibrillation: nationwide data covering the entire Korean population’, Gregory Y.H. Lip and colleagues from the University of Birmingham in the UK investigated this association in 246 459 oral anticoagulant-naïve non-valvular atrial fibrillation patients.13 One-year increase of hypertension duration continuously increased the adjusted risk of ischaemic stroke. While the risk of ischaemic stroke increased with hypertension duration in patients younger than 65 years, it reached a plateau in those aged 65 years or older. Baseline and systolic blood pressure and its durarion prior to atrial fibrillation was associated with a higher ischaemic stroke risk. However, the effect of long-term hypertension was not observed in patients with strictly controlled systolic blood pressure of <120 mmHg prior to atrial fibrillation. Thus, while hypertension duration increases the risk of ischaemic stroke, strict systolic blood pressure control attenuates it. Catheter ablation is considered the treatment of choice for many tachyarrhythmias,14,15 but convincing ‘real-world’ data on efficacy and safety are lacking. In their article ‘A decade of catheter ablation of cardiac arrhythmias in Sweden: ablation practices and outcomes’, Fredrik Holmqvist and colleagues from the Lund University in Sweden used their national registry report on the procedural characteristics and efficacy in 26 642 patients undergoing 34 428 ablations.10 The spectrum of treated arrhythmias changed over time, with a gradual increase in atrial fibrillation, ventricular tachycardia, and premature ventricular contraction (PVC) ablation, while procedural time and use of fluoroscopy decreased. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in atrial fibrillation (41% within 3 years). The rate of reported adverse events was low at 1.7%. Death in the immediate period following ablation was extremely rare (0.34%). Thus, catheter ablations have shifted towards more complex procedures, less fluoroscopy time, and increased efficacy for atrial fibrillation over the past decade. Unexplained sudden cardiac death may be attributable to a genetic cause which can be further evaluated by clinical examination of at-risk relatives towards inherited16,17 or primary arrhythmia syndromes,18–21 respectively. In their article entitled ‘Insights into sudden cardiac death: exploring the potential relevance of non-diagnostic autopsy findings’, Hariharan Raju and colleagues from the Macquarie University Faculty of Medicine and Health Sciences in NSW Australia investigated the relevance of non-diagnostic pathological abnormalities of indeterminate causality, such as myocardial hypertrophy, fibrosis, or inflammatory infiltrates, to sudden cardiac death.22 Ninety-eight at-risk relatives of unexplained sudden cardiac death cases without cardiac disease in the presence of either normal and negative or isolated non-diagnostic cardiac autopsy findings were referred to the regional unexplained sudden cardiac death clinic for phenotyping. A genetic cardiac diagnosis was established in 25% of the families (Figure 1). Uncertain sudden unexplained death and true sudden arrhythmic death syndrome explained by familial cardiogenetic diagnoses were found in 20% and 31%, respectively, with primary arrhythmia syndromes predominating. Unexplained sudden cardiac death cases were more likely than matched non-cardiac premature death controls to demonstrate at least one uncertain autopsy finding. Thus, at-risk relatives of uncertain sudden unexplained death cases should be evaluated for phenotypic evidence of both ion channel disorders and cardiomyopathies. These findings are put into context in a comprehensive Editorial by Arthur Wilde from the Academic Medical Centre in Amsterdam, The Netherlands.23 Diagnostic yield of cardiogenetic disease following cardiological evaluation of blood relatives of unexplained sudden cardiac death probands with normal (left; true SADS) and non-diagnostic (right; uncertain SUD) cardiac autopsy findings. No significant differences between proportions were identified with cardiogenetic disease (P = 0.34). BrS, Brugada syndrome; DCM, dilated cardiomyopathy; LQT, long QT syndrome; PCCD, progressive cardiac conduction disease; SADS, sudden arrhythmic death syndrome; SQT, short QT syndrome; SUD, sudden unexplained death (from Raju H, Parsons S, Thompson TN, Morgan N, Zentner D, Trainer AH, James PA, Winship IM, Kalman JM, Vohra J. Insights into sudden cardiac death: exploring the potential relevance of non-diagnostic autopsy findings. See pages 831--838). Short QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain of function in HERG/IKr.24,25 Patients develop atrial fibrillation, ventricular tachycardia, and sudden cardiac death, with pronounced interindividual variability in phenotype. In their article ‘Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility’, Katja E. Odening and colleagues from the Heart Center University of Freiburg in Germany generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling.26 Transgenic rabbits were generated by oocyte microinjection of beta-myosin-heavy-chain-promoter-KCNH2/HERG-N588K constructs. The QT interval was shorter and the QT/RR slope was shallower in SQT1 than in the wild type. Atrial and ventricular refractoriness and action potential duration were shortened, and ventricular tachycardia and fibrillation inducibility increased in SQT1. Systolic function was unaltered, but diastolic relaxation was enhanced in SQT1. IKr-steady was increased with impaired inactivation in SQT1, while IKr-tail was reduced. Quinidine prolonged or normalized QT and APD in SQT1 by reducing IKr. Diverse electrical remodelling was observed: in SQT1, IK1 was decreased—partially reversing the phenotype—while a small increase in IKs may partly contribute to an accentuation of the phenotype (Figure 2). Thus, SQT1 rabbits mimic the human disease phenotype on all levels, with shortened QT/APD and increased ventricular tachycardia and fibrillation inducibility, and show similar beneficial responses to quinidine, indicating their value for elucidation of arrhythmogenic mechanisms and identification of novel anti-arrhythmic strategies. The findings are discussed in an interesting Editorial by Carol Remme from the Academic Medical Centre in Amsterdam, The Netherlands.27 The consequences of the expression of the b-MyHC-FLAG-HA-KCNH2/HERG-N588K construct (middle) in rabbit cardiomyocytes are indicated with red arrows: the expression leads to increased IKr steady in cardiomyocytes (top) → leading to (follow arrows counterclock-wise) shortened APD in cardiomyocytes (top left) → shortened QT in vivo (below) → inducible VT/VF (bottom) → resulting in increased sudden death as indicated in Kaplan Meier curve (right bottom). The expression also results in electrical remodeling (follow arrow clock-wise) partly increasing, partly reversing the cellular phenotype (top right). In the middle right, a first example of anti-arrhythmic drug testing is provided, demonstrating beneficial QT-prolonging effects by quinidine (from Odening KE, Bod I, Franke G, Rieke R, Ryan de Medeiros A, Perez-Feliz S, Fürniss H, Mettke L, Michaelides K, Lang CN, Steinfurt J, Pantulu ND, Ziupa D, Menza M, Zehender M, Bugger H, Peyronnet R, Behrends JC, Doleschall Z, Zur Hausen A, Bode C, Jolivet G, Brunner M. Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility. See pages 842--853). This issue is complemented by a Discussion Forum contribution. In their contribution entitled ‘Fluoroscopy times in electrophysiology and device procedures: impact of single frame location fluoroscopy’ Vinit Sawhney and colleagues from the St Bartholomew’s Hospital in the UK comment on the recently published manuscript entitled ‘The dream of near-zero X-rays ablation comes true’ by Matteo Anselmino from the University of Turin in Italy.28,29 The editors hope that this issue of the European Heart Journal will be of interest to its readers. With thanks to Amelia Meier-Batschelet for help with compilation of this article.