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The pathogenic mutation p.Arg14del in the gene encoding Phospholamban (PLN) is known to cause cardiomyopathy and leads to increased risk of sudden cardiac death. Automatic tools might improve the detection of patients with this rare disease. Deep learning is currently the state-of-the-art in signal processing but requires large amounts of data to train the algorithms. In situations with relatively small amounts of data, like PLN, transfer learning may improve accuracy. We propose an ECG-based detection of the PLN mutation using transfer learning from a model originally trained for sex identification. The sex identification model was trained with 256,278 ECGs and subsequently finetuned for PLN detection (155 ECGs of patients with PLN) with two control groups: a balanced age/sex matched group and a randomly selected imbalanced population. The data was split in 10 folds and 20% of the training data was used for validation and early stopping. The models were evaluated with the area under the receiver operating characteristic curve (AUROC) of the testing data. We used gradient activation for explanation of the prediction models. The models trained with transfer learning outperformed the models trained from scratch for both the balanced (AUROC 0.87 vs AUROC 0.71) and imbalanced (AUROC 0.0.90 vs AUROC 0.65) population. The proposed approach was able to improve the accuracy of a rare disease detection model by transfer learning information from a non-manual annotated and abundant label with only limited data available., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Prior to the recognition of distinct clinical entities, such as Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and long QT syndrome, all sudden cardiac arrest (SCA) survivors with ventricular fibrillation (VF) and apparently structurally normal hearts were labelled as idiopathic ventricular fibrillation (IVF). Over the last three decades, the definition of IVF has changed substantially, mostly as result of the identification of the spectrum of SCA-predisposing genetic heart diseases (GHDs), and the molecular evidence, by post-mortem genetic analysis (aka, the molecular autopsy), of cardiac channelopathies as the pathogenic basis for up to 35% of unexplained cases of sudden cardiac death (SCD) in the young. The evolution of the definition of IVF over time has led to a progressively greater awareness of the need for an extensive diagnostic assessment in unexplained SCA survivors. Nevertheless, GHDs are still underdiagnosed among SCA survivors, due to the underuse of pharmacological challenges (i.e. sodium channel blocker test), misrecognition of electrocardiogram (ECG) abnormalities/patterns (i.e. early repolarization pattern or exercise-induced ventricular bigeminy) or errors in the measurement of ECG parameters (e.g. the heart-rate corrected QT interval). In this review, we discuss the epidemiology, diagnostic approaches, and the controversies related to role of the genetic background in unexplained SCA survivors with a default diagnosis of IVF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The spectrum of inherited arrhythmogenic diseases (IADs) includes disorders without overt structural abnormalities (i.e. primary inherited arrhythmia syndromes) and structural heart diseases (i.e. arrhythmogenic ventricular cardiomyopathy, hypertrophic cardiomyopathy). The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate current clinical practice and adherence to 2015 European Society of Cardiology Guidelines regarding the management of patients with IADs. A 24-item centre-based online questionnaire was presented to the EHRA Research Network Centres and the European Cardiac Arrhythmia Genetics Focus Group members. There were 46 responses from 20 different countries. The survey revealed that 37% of centres did not have any dedicated unit focusing on patients with IADs. Provocative drug challenges were widely used to rule-out Brugada syndrome (BrS) (91% of centres), while they were used in a minority of centres during the diagnostic assessment of long-QT syndrome (11%), early repolarization syndrome (12%), or catecholaminergic polymorphic ventricular tachycardia (18%). While all centres advised family clinical screening with electrocardiograms for all first-degree family members of patients with IADs, genetic testing was advised in family members of probands with positive genetic testing by 33% of centres. Sudden cardiac death risk stratification was straightforward and in line with current guidelines for hypertrophic cardiomyopathy, while it was controversial for other diseases (i.e. BrS). Finally, indications for ventricular mapping and ablation procedures in BrS were variable and not in agreement with current guidelines in up to 54% of centres., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

BACKGROUND Implantable cardioverter-defibrillators (ICDs) have become widely, used for the prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM), but the efficacy of this therapy in relation to risk profile has not been documented. OBJECTIVE To survey the incidence of ICD intervention in relation to demographic and clinical characteristics and risk factors in patients with HCM. DESIGN This observational, registry-based study included patients with a diagnosis of HCM who had undergone ICD implantation between 1986 and 2003 at 1 of 42 treatment centers in Australia, Europe, and the USA. Primary prevention of SCD via ICD implantation was indicated in HCM patients with any of the following risk factors: previous unexplained syncope of non-neurocardiogenic origin, massive left ventricular (LV) hypertrophy (maximum wall thickness ≥30mm), SCD in at least one first-degree relative aged younger than 50 years, and at least one episode of ventricular tachycardia confirmed by 24h ambulatory Holter monitoring. Patients received an ICD for secondary prevention if they had previously experienced a cardiac arrest. ICD discharges were deemed appropriate if activated by ventricular tachycardia or ventricular fibrillation. Interventions caused by sinus tachycardia, supraventricular arrhythmia, or device failure were classified as inappropriate. OUTCOME MEASURE The primary end point was appropriate ICD discharge within 5 years of implantation. RESULTS The study included 506 patients. Mean age at device implantation was 42 years, but, notably, 28% of patients were aged 30 years or younger at intervention. After a mean follow-up of 3.7 years, 20% of the entire cohort had experienced an appropriate ICD discharge. The probability of intervention at 5 years was 23% and the annual appropriate intervention rate was 5.5%. The mean age at first appropriate discharge was 44 years; however, 35% of those who had an ICD implanted before the age of 15 years experienced an appropriate intervention by 18 years of age. Inappropriate interventions were experienced by 27% of patients. In the primary prevention (n=383) and secondary prevention (n=123) groups, 13% and 42%, respectively, experienced an appropriate ICD shock. Notably, 27% of patients receiving amiodarone received an appropriate discharge, compared with 20% of those taking disopyramide and 15% of those on 13-blockers. Notably, patients who had undergone alcohol septal ablation had a higher rate of ICD interventions than did those who received surgical septal myectomy (10.3% per year vs 2.6% per year; P = 0.04). The authors found no significant correlation between the number of risk factors present and the probability of ICD intervention. Complications were most-commonly caused by problems with the ICD (6.7%), infection (3.8%), and hemorrhage or thrombosis (1.6%). Survival was high among this patient population, with 92% alive at the end of follow-up. Death was unrelated to HCM in 49% of those who died during the study. CONCLUSION ICDs are highly effective for the prevention of SCD in patients with HCM, and have particular utility for primary prevention in those with only one risk factor, and the very young. [ABSTRACT FROM AUTHOR]

Aims: Mutations in the Lamin A/C gene may cause atrioventricular block, supraventricular arrhythmias, ventricular arrhythmias (VA), and dilated cardiomyopathy. We aimed to explore the predictors and the mechanisms of VA in Lamin A/C mutation-positive subjects., Methods and Results: We included 41 Lamin A/C mutation-positive subjects. PR-interval and occurrence of VA were recorded. Left ventricular (LV) myocardial function was assessed as ejection fraction and speckle tracking longitudinal strain by echocardiography. Magnetic resonance imaging was performed to assess fibrosis in a selection of subjects. Ventricular arrhythmias were documented in 21 patients (51%). Prolonged PR-interval was the best predictor of VA (P < 0.001). Myocardial function by strain was reduced in the interventricular septum compared with the rest of the LV segments (-16.7% vs. -18.7%, P = 0.001) and correlated to PR-interval (R = 0.41, P = 0.03). Myocardial fibrosis was found exclusively in the interventricular septum and only in patients with VA (P = 0.007). PR-interval was longer in patients with septal fibrosis compared with those without (320 ± 66 vs. 177 ± 40 ms, P < 0.001)., Conclusion: Prolonged PR-interval was the best predictor of VA in Lamin A/C mutation-positive subjects. Electrical, mechanical, and structural cardiac properties were related in these subjects. Myocardial function was most reduced in the interventricular septum and correlated to prolonged PR-interval. Myocardial septal fibrosis was associated with prolonged PR-interval and VA. Localized fibrosis in the interventricular septum may be the mechanism behind reduced septal function, atrioventricular block and VA in Lamin A/C mutation-positive subjects.

Aims: Sudden cardiac death (SCD) in the young is a devastating event and often due to an underlying genetic heart disease. Managing these families is complicated by uncertainty regarding clinical management and profound grief. This study sought to evaluate psychological wellbeing and experiences of at-risk relatives following SCD in the young., Methods: Relatives who attended a specialized clinic following the SCD of a relative were invited to complete the Hospital Anxiety and Depression Scale (HADS) and a series of open-ended questions. Primary outcome measures were the HADS anxiety and depression subscales and a thematic qualitative analysis of the open-ended responses was performed. Clinical and genetic data were collected from the medical record., Results: Fifty relatives from 29 families returned surveys. The mean time since death was 4±2 years (mean age at death 23±10 years, 79% males). There was significant impairment in mean anxiety (8.7±4.3, p<0.0001) and depression (5.8±3.6, p<0.0001) scores compared to the general population. Mothers showed significantly impaired anxiety (10.9±4.0, p=0.001) and depression (7.3±3.3, p=0.001) scores, with 53% having an anxiety score above 11 suggesting probable anxiety disorder. Participants revealed a number of factors that have helped and hindered their ability to cope with the death, and their decisions relating to clinical screening., Conclusion: The SCD of a young relative has significant and long-term emotional implications for the family, particularly for the mother.