Novel electrocardiographic criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy

Aims: In order to improve the electrocardiographic (ECG) diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC), we evaluated novel quantitative parameters of the QRS complex and the value of bipolar chest leads (CF leads) computed from the standard 12 leads. Methods and results: We analysed digital 12-lead ECGs in 44 patients with ARVC, 276 healthy subjects including 44 age and sex-matched with the patients and 36 genotyped members of ARVC families. The length and area of the terminal S wave in V1 to V3 were measured automatically using a common for all 12 leads QRS end. T wave negativity was assessed in V1 to V6 and in the bipolar CF leads computed from the standard 12 leads. The length and area of the terminal S wave were significantly shorter, whereas the S wave duration was significantly longer in ARVC patients compared with matched controls. Among members of ARVC families, those with mutations (n = 15) had shorter QRS length in V2 and V3 and smaller QRS area in lead V2 compared with those without mutations (n = 20). In ARVC patients, the CF leads were diagnostically superior to the standard unipolar precordial leads. Terminal S wave duration in V1 >48 ms or major T wave negativity in CF leads separated ARVC patients from matched controls with 90% sensitivity and 86% specificity. Conclusion: The terminal S wave length and area in the right precordial leads are diagnostically useful and suitable for automatic analysis in ARVC. The CF leads are diagnostically superior to the unipolar precordial leads

Low Prevalence of Risk Markers in Cases of Sudden Death Due to Brugada Syndrome Relevance to Risk Stratification in Brugada Syndrome

ObjectivesThe objective of this study was to determine the prevalence of conventional risk factors in sudden arrhythmic death syndrome (SADS) probands with Brugada syndrome (BrS).BackgroundPatients with BrS and previous aborted sudden cardiac death (SCD) are at high risk of recurrent events. Other universally accepted clinical features associated with higher risk include unheralded syncope and the presence of a spontaneous type 1 electrocardiogram (ECG).MethodsWe analyzed reported symptoms and reviewed ECGs from SADS probands with familial diagnoses of BrS, established by cardiological evaluation, including ECG, 2-dimensional echocardiography, Holter monitoring, exercise tolerance testing, and ajmaline provocation. These cases underwent familial evaluation between 2003 and 2010.ResultsA total of 49 consecutive families with a confirmed SADS death and a diagnosis of BrS were evaluated, comprising assessment of 202 family members in total. One family had 2 members with SADS, resulting in a total of 50 probands included. Mean age of death of probands was 29.1 ± 10.6 years, with 41 males (82%) (p < 0.05). Antemortem ECGs were available for 5 SADS probands, 1 of which demonstrated a spontaneous type 1 pattern. In 45 probands, symptoms before death were reported reliably by family members. Of these, 9 (20%) had experienced at least 1 syncopal episode before the fatal event. Importantly, 68% of probands would not have fulfilled any current criteria for consideration of implantable cardioverter-defibrillator.ConclusionsThe “low-risk” asymptomatic BrS group comprises the majority of SCD in this cohort. Current risk stratification would appear to be inadequate, and new markers of risk are vital

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis

Genome Wide Analysis of Drug-Induced Torsades de Pointes: Lack of Common Variants with Large Effect Sizes

Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP), treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of ≥2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP) by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p  =  3×10(-7), odds ratio = 2, 95% confidence intervals: 1.5-2.6). The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p  =  3×10(-9)). Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs

Brugada syndrome

The Brugada syndrome demonstrates characteristic electrocardiogram features and is a significant cause of sudden death in young adults with overtly normal cardiac structure and function. The genetic basis has not yet been fully elucidated but our understanding of the causative mutations and modifiers of arrhythmic events is advancing rapidly alongside sequencing technologies. We expect that the future will include risk stratification according to genotype and management tailored to the genetic diagnosis

An undiagnosed bicuspid aortic valve can result in severe left ventricular failure

Asymptomatic bicuspid aortic valves diagnosed in childhood need regular monitoring to allow early surgical intervention and prevention of left ventricular failur