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BACKGROUND: The subcutaneous ICD (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. The PRAETORIAN trial demonstrated that the S-ICD is non-inferior to the TV-ICD with regard to the combined primary endpoint of inappropriate shocks and complications. This prespecified secondary analysis evaluates all complications in the PRAETORIAN trial. METHODS: The PRAETORIAN trial is an international, multicenter, randomised trial in which 849 patients with an indication for ICD therapy were randomised to receive an SICD (N = 426) or TV-ICD (N = 423) and followed for a median of 49 months. Endpoints were device-related complications, lead-related complications, systemic infections and the need for invasive interventions. RESULTS: Thirty-six device-related complications occurred in 31 patients in the S-ICD group of which bleedings were the most frequent. In the TV-ICD group 49 complications occurred in 44 patients of which lead-dysfunction was most frequent (HR 0.69; P =0.11). In both groups half of all complications were within 30 days after implantation. Lead-related complications and systemic infections occurred significantly less in the S-ICD group compared to the TV-ICD group (P

Genetic testing has advanced significantly since the publication of the 2011 HRS/EHRA Expert Consensus Statement on the State of Genetic Testing for the Channelopathies and Cardiomyopathies.1 In addition to single-gene testing, there is now the ability to perform whole-exome sequencing (WES) and whole-genome sequencing (WGS). There is growing appreciation of oligogenic disorders,2,3 the role of modifier genes,2 and the use of genetic testing for risk stratification, even in common cardiac diseases such as coronary artery disease or atrial fibrillation (AFib), including a proposal for a score awaiting validation.4 This document reviews the state of genetic testing at the present time, and addresses the questions of what tests to perform and when to perform them. It should be noted that, as articulated in a 1999 Task Force Document by the European Society of Cardiology (ESC) on the legal value of medical guidelines,5 ‘The guidelines from an international organization, such as the ESC, have no specific legal territory and have no legally enforcing character. Nonetheless, in so far as they represent the state-of-the-art, they may be used as indicating deviation from evidence-based medicine in cases of questioned liability’. In the case of potentially lethal and treatable conditions such as catecholaminergic polymorphic ventricular tachycardia (CPVT) or long QT syndrome (LQTS), it is the responsibility of the physician, preferably in conjunction with an expert genetics team, to communicate to the patient/family the critical importance of family screening, whether this be facilitated by cascade genetic testing or by broader clinical family screening

Andersen Tawil Syndrome (ATS) is a neurological channelopathy caused by mutations in the KCNJ2 gene that encodes the ubiquitously expressed Kir2.1 potassium channel. The syndrome is characterised by episodic weakness, cardiac arrythmias and dysmorphic features. However, the full extent of the multi-system phenotype is not well described. In-depth, multi-system phenotyping is required to inform diagnosis, and guide management. We report our findings following deep multimodal phenotyping across all systems in a large case series of 69 total patients, with comprehensive data for 52. As a national referral centre, we assessed point prevalence and showed it is higher than previously reported, at 0.105 per 100 000 population in England. While the classical phenotype of episodic weakness is recognised, we found that a quarter of our cohort have fixed myopathy and 13.5% required a wheelchair or gait aid. We identified frequent fatty infiltration on MRI and tubular aggregates on muscle biopsy emphasising the active myopathic process underpinning the potential for severe neuromuscular disability. Long exercise testing (LET) was not reliable in predicting neuromuscular symptoms. A normal LET was seen in five patients of whom four had episodic weakness. 67% of patients treated with acetazolamide reported a good neuromuscular response. 13% of the cohort required cardiac defibrillator or pacemaker insertion. An additional 23% reported syncope. Baseline electrocardiograms were not helpful in stratifying cardiac risk, but holter monitoring was. A subset of patients had no cardiac symptoms, but had abnormal holter monitor recordings which prompted medication treatment. We describe the utility of loop recorders to guide management in two such asymptomatic patients. Micrognathia was the most commonly reported skeletal feature, however 8% of patients did not have dysmorphic features and one third of patients had only mild dysmorphic features. We describe novel phenotypic features including abnormal echocardiogram in nine patients, prominent pain, fatigue and fasciculations. Five patients exhibited executive dysfunction and slowed processing which may be linked to central expression of KCNJ2. We report eight new KCNJ2 variants with in vitro functional data. Our series illustrates that ATS is not benign. We report marked neuromuscular morbidity and cardiac risk with multi-system involvement. Our key recommendations include proactive genetic screening of all family members of a proband. This is required, given the risk of cardiac arrhythmias among asymptomatic individuals, and a significant subset of ATS patients have no (or few) dysmorphic features or negative LET. We discuss recommendations for increased cardiac surveillance and neuropsychometry testing.

Background\ud The diagnosis of arrhythmogenic cardiomyopathy (ACM) is challenging especially in children at risk of adverse events. Analysis of cardiac myocyte junctional protein distribution may have diagnostic and prognostic implications, but its utility is limited by the need for a myocardial sample. We previously reported that buccal mucosa cells show junctional protein redistribution similar to that seen in cardiac myocytes of adult patients with ACM.\ud \ud Objectives\ud We aimed to determine when junctional protein distribution abnormalities first occur in children with ACM variants and whether they correlate with progression of clinically apparent disease.\ud \ud Methods\ud We analyzed buccal mucosa samples of children and adolescents with a family history of ACM (n = 13) and age-matched controls (n = 13). Samples were immunostained for plakoglobin, desmoplakin, plakophilin-1 and connexin43 and analyzed by confocal microscopy. All participants were swabbed at least twice with an average interval of 12–18 months between samplings.\ud \ud Results\ud Junctional protein re-localization in buccal mucosa cells did not correlate with the presence of ACM-causing variants but instead occurred with clinical onset of disease. No changes in protein distribution were seen unless and until there was clinical evidence of disease. In addition, progressive shifts in the distribution of key proteins correlated with worsening of the disease phenotype. Finally, we observed restoration of junctional signal for Cx43 in patient with a favorable response to anti-arrhythmic therapy.\ud \ud Conclusions\ud Due to ethical concerns about obtaining heart biopsies in children with no apparent disease, it has not been possible to analyze molecular changes in cardiac myocytes with the onset/progression of clinical disease. Using buccal smears as a surrogate for the myocardium may facilitate future studies of mechanisms and pathophysiological consequences of junctional protein redistribution in ACM. Buccal cells may also be a safe and inexpensive tool for risk stratification and potentially monitoring response to treatment in children bearing ACM variants.

INTRODUCTION: Before ablation, predicting the site of origin (SOO) of outflow tract ventricular arrhythmia (OTVA), can inform patient consent and facilitate appropriate procedural planning. We set out to determine if OTVA variability can accurately predict SOO. METHODS: Consecutive patients with a clear SOO identified at OTVA ablation had their prior 24-h ambulatory ECGs retrospectively analysed (derivation cohort). Percentage ventricular ectopic (VE) burden, hourly VE values, episodes of trigeminy/bigeminy, and the variability in these parameters were evaluated for their ability to distinguish right from left-sided SOO. Effective parameters were then prospectively tested on a validation cohort of consecutive patients undergoing their first OTVA ablation. RESULTS: High VE variability (coefficient of variation ≥0.7) and the presence of any hour with

Aims Since its emergence in early 2020, the novel severe acute respiratory syndrome coronavirus 2 causing coronavirus disease 2019 (COVID-19) has reached pandemic levels, and there have been repeated outbreaks across the globe. The aim of this two-part series is to provide practical knowledge and guidance to aid clinicians in the diagnosis and management of cardiovascular disease (CVD) in association with COVID-19. Methods and results A narrative literature review of the available evidence has been performed, and the resulting information has been organized into two parts. The first, reported here, focuses on the epidemiology, pathophysiology, and diagnosis of cardiovascular (CV) conditions that may be manifest in patients with COVID-19. The second part, which will follow in a later edition of the journal, addresses the topics of care pathways, treatment, and follow-up of CV conditions in patients with COVID-19. Conclusion This comprehensive review is not a formal guideline but rather a document that provides a summary of current knowledge and guidance to practicing clinicians managing patients with CVD and COVID-19. The recommendations are mainly the result of observations and personal experience from healthcare providers. Therefore, the information provided here may be subject to change with increasing knowledge, evidence from prospective studies, and changes in the pandemic. Likewise, the guidance provided in the document should not interfere with recommendations provided by local and national healthcare authorities. [GRAPHICS] .

Supplemental Digital Content is available in the text., Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. Methods: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. Results: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54–13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39–51.24; P

Brugada syndrome (BrS) was first described as a primary electrical disorder predisposing to the risk of sudden cardiac death and characterized by right precordial lead ST elevation. Early description of right ventricular structural abnormalities and of right ventricular outflow tract (RVOT) conduction delay in BrS patients set the stage for the current controversy over the pathophysiology underlying the syndrome: channelopathy or cardiomyopathy; repolarization or depolarization. This review examines the current understanding of the BrS substrate, its genetic and non-genetic basis, theories of pathophysiology, and the clinical implications thereof. We propose that the final common pathway for BrS could be viewed as a disease of 'reduced RVOT conduction reserve'.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.

This international multidisciplinary document intends to provide clinicians with evidence-based practical patient-centered recommendations for evaluating patients and decedents with (aborted) sudden cardiac arrest and their families. The document includes a framework for the investigation of the family allowing steps to be taken, should an inherited condition be found, to minimize further events in affected relatives. Integral to the process is counseling of the patients and families, not only because of the emotionally charged subject, but because finding (or not finding) the cause of the arrest may influence management of family members. The formation of multidisciplinary teams is essential to provide a complete service to the patients and their families, and the varied expertise of the writing committee was formulated to reflect this need. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by Class of Recommendation and Level of Evidence. The recommendations were opened for public comment and reviewed by the relevant scientific and clinical document committees of the Asia Pacific Heart Rhythm Society (APHRS) and the Heart Rhythm Society (HRS); the document underwent external review and endorsement by the partner and collaborating societies. While the recommendations are for optimal care, it is recognized that not all resources will be available to all clinicians. Nevertheless, this document articulates the evaluation that the clinician should aspire to provide for patients with sudden cardiac arrest, decedents with sudden unexplained death, and their families.

Background:\ud Triadin knockout syndrome (TKOS) is a potentially lethal arrhythmia disorder caused by recessively inherited null variants in TRDN-encoded cardiac triadin. Despite its malignant phenotype, the prevalence of TKOS in sudden infant death syndrome and sudden unexplained death in the young is unknown.\ud \ud Methods:\ud Exome sequencing was performed on 599 sudden infant death syndrome and 258 sudden unexplained death in the young cases. Allele frequencies of all TRDN null variants identified in the cardiac-specific isoform of TRDN in the Genome Aggregation Database were used to determine the estimated prevalence and ethnic distribution of TKOS.\ud \ud Results:\ud No triadin null individuals were identified in 599 sudden infant death syndrome and 258 sudden unexplained death in the young exomes. Using the Genome Aggregation Database, we estimate the overall prevalence of TKOS to be ≈1:22.7 million individuals. However, TKOS prevalence is 5.5-fold higher in those of African descent (≈1:4.1 million).\ud \ud Conclusions:\ud TKOS is an exceedingly rare clinical entity that does not contribute meaningfully to either sudden infant death syndrome or sudden unexplained death in the young. However, despite its rarity and absence in large sudden death cohorts, TKOS remains a malignant and potentially lethal disorder which requires further research to better care for these patients.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically determined heart muscle disorder associated with an increased risk of life-threatening arrhythmias in some patients. Risk stratification remains challenging. Therefore, we sought a non-invasive, easily applicable risk score to predict sustained ventricular arrhythmias in these patients. METHODS: Cohort of Patients who fulfilled the 2010 ARVC task force criteria were consecutively recruited. Detailed clinical data were collected at baseline and during follow up. The clinical endpoint was a composite of recurrent sustained ventricular arrhythmias and hospitalization due to ventricular arrhythmias. Multivariable logistic regression was used to develop models to predict the arrhythmic risk. A cohort including patients from other registries in UK, Canada and Switzerland was used as a validation population. RESULTS: One hundred and thirty-five patients were included of whom 35 patients (31.9%) reached the endpoint. A model consisting of filtered QRS duration on signal-averaged ECG, non-sustained VT (NSVT) on 24 h-ECG, and absence of negative T waves in lead aVR on 12‑lead surface ECG was able to predict arrhythmic events with a sensitivity of 81.8%, specificity of 84.0% and a negative predictive value of 95.5% at the first presentation of the disease. This risk score was validated in international ARVC registry patients. CONCLUSION: A risk score consisting of a filtered QRS duration ≥117 ms, presence of NSVT on 24 h-ECG and absence of negative T waves in lead aVR was able to predict arrhythmic events at first presentation of the disease.

Sudden cardiac death is defined as a death occurring usually within an hour of onset of symptoms, arising from an underlying cardiac disease. Sudden cardiac death is a complication of a number of cardiovascular diseases and is often unexpected. In individuals aged

OBJECTIVES: This study sought to describe the clinical and pathological features of anomalous origin of a coronary artery (AOCA) in sudden cardiac death (SCD) victims. BACKGROUND: AOCA from the inappropriate sinus of Valsalva or from the pulmonary artery is increasingly diagnosed with current imaging techniques. AOCA is a possible cause of SCD. METHODS: We reviewed a database of 5,100 consecutive cases of SCD referred to our specialist cardiac pathology center between January 1994 and March 2017 and identified a subgroup of 30 cases (0.6%) with AOCA. All cases underwent detailed post-mortem evaluation including histological analysis by an expert cardiac pathologist. Clinical information was obtained from referring coroners. RESULTS: The mean age was 28 ± 16 years and 23 individuals were male (77%). In 8 cases (27%), SCD occurred before 18 years of age. Cardiac symptoms were present in 11 individuals (37%), and syncope was the most common (n = 6, 20%). Anomalous left coronary artery arising from the right sinus of Valsalva (ALCA) with interarterial course (n = 11) and anomalous right coronary artery arising from the left sinus of Valsalva (ARCA) with interarterial course (n = 11) were the most common found. ALCA arising from pulmonary artery was present in 7 cases, whereas in 1 case, the left coronary artery arose from the noncoronary cusp. Left ventricular fibrosis was reported in 11 cases (37%) and was mainly subendocardial. There was evidence of acute infarction in 2 cases. Death occurred during exercise or emotional stress in 15 (50%) cases. The AOCA variant where death occurred more frequently during physical activity was ALCA (8 of 11, 73%), followed by ALCA arising from pulmonary artery (4 of 7, 57%) and ARCA (2 of 11, 18%). CONCLUSIONS: AOCA is a rare cause of SCD. ALCA and ARCA with interarterial course are the most common anatomical variants recognized at the postmortem of SCD victims. ALCA is more commonly associated with death during exercise. Cardiac arrhythmias causing sudden death seem most likely in the cases without overt myocardial damage.

BACKGROUND: Potentially lethal cardiac channelopathies/cardiomyopathies may underlie a substantial portion of sudden unexplained death in the young (SUDY). The whole-exome molecular autopsy represents the latest approach to postmortem genetic testing for SUDY. However, proper variant adjudication in the setting of SUDY can be challenging. METHODS: From January 2012 through December 2013, 25 consecutive cases of SUDY from 1 to 40 years of age (average age at death 27±5.7 years; 13 white, 12 black) from Cook County, Illinois, were referred after a negative (n=16) or equivocal (n=9) conventional autopsy. A whole-exome molecular autopsy with analysis of 99 sudden death-susceptibility genes was performed. The predicted pathogenicity of ultrarare, nonsynonymous variants was determined using the American College of Medical Genetics guidelines. RESULTS: Overall, 27 ultrarare nonsynonymous variants were seen in 16/25 (64%) victims of SUDY. Among black individuals, 9/12 (75%) had an ultrarare nonsynonymous variant compared with 7/13 (54%) white individuals. Of the 27 variants, 10 were considered pathogenic or likely pathogenic in 7/25 (28%) individuals in accordance with the American College of Medical Genetics guidelines. Pathogenic/likely pathogenic variants were identified in 5/16 (31%) of autopsy-negative cases and in 2/6 (33%) victims of SUDY with equivocal findings of cardiomyopathy. Overall, 6 pathogenic/likely pathogenic variants in 4/25 (16%) cases were congruent with the phenotypic findings at autopsy and therefore considered clinically actionable. CONCLUSIONS: Whole-exome molecular autopsy with gene-specific surveillance is an effective approach for the detection of potential pathogenic variants in SUDY cases. However, systematic variant adjudication is crucial to ensure accurate and proper care for surviving family members.

BACKGROUND: Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS. OBJECTIVES: This study aimed to determine the spectrum and prevalence of GHD-associated mutations as a potential monogenic basis for SIDS. METHODS: A cohort of 419 unrelated SIDS cases (257 male; average age 2.7 ± 1.9 months) underwent whole exome sequencing and a targeted analysis of 90 GHD-susceptibility genes. The yield of "potentially informative," ultra-rare variants (minor allele frequency

Sudden cardiac death in the young is a devastating event and a significant proportion of cases are caused by an underlying inherited cardiac condition. This justifies investigation of surviving blood relatives in order to identify a definite diagnosis and to prevent further deaths. First-degree relatives, obligate carriers, and symptomatic relatives are family members who are more likely to be affected and/or at risk and should be prioritized for evaluation. Cardiological clinical evaluation of family members is staged, less invasive investigations being first offered and more invasive tests being subsequently considered if a diagnosis is not made. If a phenotype is identified, then targeted genetic testing can be undertaken. Results of post-mortem genetic testing (the molecular autopsy) in the decedent may confirm familial results or guide cascade testing in order to identify presymptomatic individuals. When a genetic diagnosis is made in the sudden death case, initial familial genetic testing should focus on the parents to determine whether the mutation is inherited, or arose de novo in the deceased. Management of the surviving family and genetic counselling should be offered in the setting of a specialized, multidisciplinary cardiac genetic team to offer the most accurate care and support to family members. Further research into understanding the genetic basis of sudden cardiac death and new diagnostic modalities will contribute to improve management and prevention of sudden cardiac death in the young.

BACKGROUND: There is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease. OBJECTIVE: We characterised Brugada syndrome (BrS) patients using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). METHODS: BrS was diagnosed according to international guidelines. 26% BrS patients carried SCN5A mutations. CMR data from 78 BrS patients were compared with 78 healthy controls (44±15 vs 42±14 years; p=0.434 and 64% vs 64% male; p=1.000). RESULTS: Right ventricular (RV) ejection fraction was slightly lower (61±8% vs 64±5%; p=0.004) and RV end-systolic volume slightly greater (31±10mL/m(2) vs 28±6mL/m(2); p=0.038) in BrS compared with controls. These values remained within the normal range. LGE was demonstrated in 8% BrS patients (left ventricular (LV) midwall LGE in 5%) but not in controls (p=0.028). In BrS patients with midwall LGE there were no other features of cardiomyopathy at the time of CMR but genetic testing and follow-up has revealed a desmoplakin mutation in one patient and evolution of T-wave inversion throughout all precordial ECG leads in another. Neither patient fulfils diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy. CONCLUSION: Some BrS patients have LV midwall LGE consistent with an underlying cardiomyopathic process. Even cases without LGE show greater RV volumes and reduced RV function. These findings lend further support to the presence of subtle structural abnormalities in BrS. The BrS pattern with LGE may serve as early markers for evolution of a cardiomyopathic phenotype over time. CMR is a potentially useful adjunct investigation in the clinical evaluation of BrS.

Approximately 4% of sudden cardiac deaths are unexplained [the sudden arrhythmic death syndrome (SADS)], and up to 6-10% of survivors of cardiac arrest do not have an identifiable cardiac abnormality after comprehensive clinical evaluation [idiopathic ventricular fibrillation (IVF)]. Genetic testing may be able to play a role in diagnostics and can be targeted to an underlying phenotype present in family members following clinical evaluation. Alternatively, post-mortem genetic testing (the "molecular autopsy") may diagnose the underlying cause if a clearly pathogenic rare variant is found. Limitations include a modest yield, and the high probability of finding a variant of unknown significance (VUS) leading to a low signal-to-noise ratio. Next generation sequencing enables cost-efficient high throughput screening of a larger number of genes but at the expense of increased genetic noise. The yield from genetic testing is even lower in IVF in the absence of any suggestion of another phenotype in the index case or his/her family, and should be actively discouraged at this time. Future improvements in diagnostic utility include optimization of the use of variant-calling pipelines and shared databases as well as patient-specific models of disease to more accurately assign pathogenicity of variants. Studying "trios" of parents and the index case may better assess the yield of sporadic and recessive disease.

Background: \ud Accurate knowledge of causes of sudden cardiac death (SCD) in athletes and its precipitating factors is necessary to establish preventative strategies.\ud Objectives: \ud This study investigated causes of SCD and their association with intensive physical activity in a large cohort of athletes.\ud Methods: \ud Between 1994 and 2014, 357 consecutive cases of athletes who died suddenly (mean 29 ± 11 years of age, 92% males, 76% Caucasian, 69% competitive) were referred to our cardiac pathology center. All subjects underwent detailed post-mortem evaluation, including histological analysis by an expert cardiac pathologist. Clinical information was obtained from referring coroners.\ud Results: \ud Sudden arrhythmic death syndrome (SADS) was the most prevalent cause of death (n = 149 [42%]). Myocardial disease was detected in 40% of cases, including idiopathic left ventricular hypertrophy (LVH) and/or fibrosis (n = 59, 16%); arrhythmogenic right ventricular cardiomyopathy (ARVC) (13%); and hypertrophic cardiomyopathy (HCM) (6%). Coronary artery anomalies occurred in 5% of cases. SADS and coronary artery anomalies affected predominantly young athletes (≤ 35 years of age), whereas myocardial disease was more common in older individuals. SCD during intense exertion occurred in 61% of cases; ARVC and left ventricular fibrosis most strongly predicted SCD during exertion.\ud Conclusions: \ud Conditions predisposing to SCD in sports demonstrate a significant age predilection. The strong association of ARVC and left ventricular fibrosis with exercise-induced SCD reinforces the need for early detection and abstinence from intense exercise. However, almost 40% of athletes die at rest, highlighting the need for complementary preventive strategies.

PURPOSE: The purpose of this study is to establish the role of Achieve Mapping Catheter in cryoablation for paroxysmal atrial fibrillation (PAF) in a randomized trial. METHODS: A total of 102 patients undergoing their first ablation for PAF were randomized at 2:1 to an Achieve- or Lasso-guided procedure. Study patients were systematically followed up for 12 months with Holter monitoring. Primary study endpoint was acute procedure success. Secondary endpoint was clinical outcomes assessed by AF free at 6 and 12 months after the procedure. RESULTS: Of 102 participants, 99 % of acute procedure success was achieved. Significantly shorter procedure duration with the Achieve-guided group than with the Lasso-guided group (118 ± 18 vs. 129 ± 21 min, p

Epidemiologic studies clearly document the public health burden of sudden unexpected death in epilepsy (SUDEP). Clinical and experimental studies have uncovered dynamic cardiorespiratory dysfunction, both interictally and at the time of sudden death due to epilepsy. Genetic analyses in humans and in model systems have facilitated our current molecular understanding of SUDEP. Many discoveries have been informed by progress in the field of sudden cardiac death and sudden infant death syndrome. It is becoming apparent that SUDEP genomic complexity parallels that of sudden cardiac death, and that there is a pauci1ty of analytically useful postmortem material. Because many challenges remain, future progress in SUDEP research, molecular diagnostics, and prevention rests in international, collaborative, and transdisciplinary dialogue in human and experimental translational research of sudden death.

Knowledge of the feeding ecology of fish is essential for understanding the functioning of freshwater communities. Here we report on an analysis of the diet of Pachyurus bonariensis Steindachner, 1879, a freshwater sciaenid. Fish were collected bimonthly from December 1999 to January 2002 at three locations along the Ibicuí River in the Rio Grande do Sul State, Brazil. At each location, the specimens were collected in both lentic and lotic environments. The stomachs of 324 fish were analysed for contents and fullness. The main items were Ephemeroptera, Diptera (larvae), Trichoptera and Odonata. Annelida, plant matter, Decapoda, Diptera (pupae), Coleoptera and Mollusca were present in small amounts. The fish consumed smaller amounts of food in winter than in other seasons. The most important source of dietary variation for P. bonariensis was the ontogenetic, related to intrinsic biological characters. However, spatial variation was also found, suggesting that this species can adapt its diet to environmental changes. Although P. bonariensis showed ontogenetic and spatial variations in the main items consumed, the main items were always insects, characterising P. bonariensis as a fish with an insectivorous feeding habit in the Ibicuí River.

Alternating hemiplegia of childhood is rare and usually results from mutations in cardiac- and brain-expressed ATP1A3. In an ECG study of 52 cases, Jaffer et al. reveal dynamic cardiac repolarisation or conduction abnormalities in over 50%. Abnormalities are more common in those ≥16 years, and suggest impaired cardiac repolarisation reserve., Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term ‘alternating hemiplegia’. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those

There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities. This paper discusses the uncertainties about available data and provides comprehensive suggestions for standard definitions and a guide for uniform registration parameters of SCA/SCD. The parameters include a definition of what constitutes an 'athlete', incidence calculations, enrolment of cases, the importance of gender, ethnicity and age of the athlete, as well as the type and level of sporting activity. A precise instruction for autopsy practice in the case of a SCD of athletes is given, including the role of molecular samples and evaluation of possible doping. Rational decisions about cardiac preparticipation screening and cardiac safety at sport facilities requires increased data quality concerning incidence, aetiology and management of SCA/SCD in sports. Uniform standard registration of SCA/SCD in athletes and leisure sportsmen would be a first step towards this goal.

Most sudden deaths are because of a cardiac etiology and are termed sudden cardiac death (SCD). In younger individuals coronary artery disease is less prevalent and cardiac genetic disorders are more common. If sudden death is unexplained despite an appropriate autopsy and toxicologic assessment the term sudden arrhythmic death syndrome (SADS) may be used. This is an umbrella term and common underlying etiologies are primary arrhythmia syndromes with a familial basis such as Brugada syndrome, long QT syndrome, and subtle forms of cardiomyopathy. The first clinical presentation of these conditions is often SCD, which makes identification, screening, and risk stratification crucial to avert further deaths. This review will focus on genetic testing in the context of family screening. It will address the role of the "molecular autopsy" alongside current postmortem practices in the evaluation of SADS deaths. We describe the current data underlying genetic testing in these conditions, explore the potential for next-generation sequencing, and discuss the inherent diagnostic problems in determination of pathogenicity.

Knowledge of the feeding ecology of fish is essential for understanding the functioning of freshwater communities. Here we report on an analysis of the diet of Pachyurus bonariensis Steindachner, 1879, a freshwater sciaenid. Fish were collected bimonthly from December 1999 to January 2002 at three locations along the Ibicuí River in the Rio Grande do Sul State, Brazil. At each location, the specimens were collected in both lentic and lotic environments. The stomachs of 324 fish were analysed for contents and fullness. The main items were Ephemeroptera, Diptera (larvae), Trichoptera and Odonata. Annelida, plant matter, Decapoda, Diptera (pupae), Coleoptera and Mollusca were present in small amounts. The fish consumed smaller amounts of food in winter than in other seasons. The most important source of dietary variation for P. bonariensis was the ontogenetic, related to intrinsic biological characters. However, spatial variation was also found, suggesting that this species can adapt its diet to environmental changes. Although P. bonariensis showed ontogenetic and spatial variations in the main items consumed, the main items were always insects, characterising P. bonariensis as a fish with an insectivorous feeding habit in the Ibicuí River. A ecologia alimentar de uma espécie é muito importante para o entendimento do funcionamento das comunidades de água doce. Neste trabalho analisamos a dieta de Pachyurus bonariensis, um sciaenídeo restrito a ambientes dulceaquícolas. Os peixes foram coletados bimestralmente de dezembro de 1999 a janeiro de 2002 em três locais do rio Ibicuí no Estado do Rio Grande do Sul, Brasil. Em cada local os espécimes foram coletados em ambiente lótico e lêntico. Estômagos de 324 indivíduos foram analisados quanto ao seu conteúdo e grau de repleção. Os principais itens foram Ephemeroptera, Diptera (larva), Trichoptera e Odonata. Os itens Anellida, matéria vegetal, Decapoda, Diptera (pupas), Coleoptera e Mollusca estiveram presentes em menor quantidade. No inverno os peixes consumiram menor quantidade de alimento, quando comparado com as demais estações. A principal fonte de variação na dieta desse sciaenídeo foi proveniente de mudanças ontogenéticas, relacionadas a fatores biológicos intrínsecos. Entretanto também foi observada variação espacial na dieta de P. bonariensis, sugerindo que essa espécie pode adaptar sua dieta a mudanças ambientais. Apesar de P. bonariensis apresentar mudanças ontogenéticas e espaciais na sua dieta, os principais itens foram sempre insetos, caracterizando essa espécie como um peixe com hábitos insetívoros no rio Ibicuí.