Background— The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown. Methods and Results— A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient’s explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes. Conclusions— In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation.

Aims: The concept of “atrial cardiomyopathy” (AtCM) had been percolating through the literature since its first mention in 1972. Since then, publications using the term were sporadic until the decision was made to convene an expert working group with representation from four multinational arrhythmia organizations to prepare a consensus document on atrial cardiomyopathy in 2016 (EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication). Subsequently, publications on AtCM have increased progressively. Methods and results: The present consensus document elaborates the 2016 AtCM document further to implement a simple AtCM staging system (AtCM stages 1–3) by integrating biomarkers, atrial geometry, and electrophysiological changes. However, the proposed AtCM staging needs clinical validation. Importantly, it is clearly stated that the presence of AtCM might serve as a substrate for the development of atrial fibrillation (AF) and AF may accelerates AtCM substantially, but AtCM per se needs to be viewed as a separate entity. Conclusion: Thus, the present document serves as a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) to contribute to the evolution of the AtCM concept.

Background — Progressive activation delay starting at long coupling intervals of premature stimuli has been shown to correlate with sudden cardiac death in patients with hypertrophic cardiomyopathy. The purpose of this study was to elucidate the mechanism of increased activation delay in chronically diseased myocardium. Methods and Results — High-resolution unipolar mapping (105, 208, or 247 recording sites with interelectrode distances of 0.8, 0.5, or 0.3 mm, respectively) of epicardial electrical activity was carried out during premature stimulation in 11 explanted human hearts. The hearts came from patients who underwent heart transplantation and were in the end stage of heart failure (coronary artery disease, 4; hypertrophic cardiomyopathy, 1; and dilated cardiomyopathy, 6). Eight hearts were Langendorff-perfused. Epicardial sheets were taken from the remaining hearts and studied in a tissue bath. Activation maps and conduction curves were constructed and correlated with histology. Conduction curves revealing prominent increase of activation delay were associated with zones of dense, patchy fibrosis with long fibrotic strands. Dense, diffuse fibrosis with short fibrotic strands only marginally affected conduction curves. The course of conduction curves in patchy fibrotic areas greatly depended on the direction of propagation relative to fiber direction. Conclusions — The study demonstrates that in chronically diseased human myocardium, nonuniform anisotropic characteristics imposed by long fibrotic strands cause a progressive increase of activation delay, starting at long coupling intervals of premature stimuli. The increase strongly depends on the direction of the wave front with respect to fiber direction and the architecture of fibrosis.

Background—: Sudden cardiac death (SCD) is a major cause of mortality in adults with congenital heart disease (CHD). The aim of this study was to determine the adult CHD population at risk of SCD and the clinical parameters associated with SCD. Methods and Results—: We performed a multicenter case-control study. Patients who died suddenly as a result of proven or presumed arrhythmia were included (cases). For each case, 2 controls matched on diagnosis, type of surgical intervention, age, and gender were included. From 3 databases including 25 790 adults with CHD, 1189 deaths (5%) were identified, of whom 213 patients (19%) died suddenly. Arrhythmic death occurred in 171 of 1189 patients. The underlying cardiac lesions were mild, moderate, and severe CHD in 12%, 33%, and 55% of the SCD cases, respectively. Clinical variables associated with SCD were supraventricular tachycardia (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.5–7.9; P= 0.004), moderate to severe systemic ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.4; P= 0.034), moderate to severe subpulmonary ventricular dysfunction (OR, 3.4; 95% CI, 1.1–10.2; P= 0.030), increased QRS duration (OR, 1.34 [per 10-ms increase]; 95% CI, 1.10–1.34; P =0.008), and QT dispersion (OR, 1.22 [per 10-ms increase]; 95% CI, 1.22–1.48; P =0.008). Conclusions—: The clinical parameters found to be associated with SCD in adults with a broad spectrum of CHD, including systemic right ventricles, are similar to those in ischemic heart disease. Moreover, even those patients with mild cardiac lesions are potentially at risk for SCD. This highlights the need for further prospective studies as well as vigilant ongoing follow-up of the adult with CHD.

Background—: Conventional cardiac pacemakers are associated with several potential short- and long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker. Methods and Results—: The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77±8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range. Conclusions—: In a prospective nonrandomized study, a completely self-contained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing. Clinical Trial Registration—: URL: http://clinicaltrials.gov . Unique identifier: NCT01700244.