Documenting the descent - remote monitoring and adult-onset Catecholaminergic Polymorphic Ventricular Tachycardia associated with ventricular fibrillation and bradycardia.

This image highlights a 38-year-old female with ventricular fibrillation and spontaneous return to sinus rhythm found on an implantable loop recorder inserted for recurrent syncope. Ultimately, she was diagnosed with catecholaminergic polymorphic ventricular tachycardia, a rare inherited arrhythmia disorder.

The many functions of the endoplasmic reticulum chaperones and folding enzymes.

Endoplasmic reticulum (ER) is an essential sub-cellular compartment of the eukaryotic cell performing many diverse functions essential for the cell and the whole organism. ER molecular chaperones and folding enzymes are multidomain proteins that are designed to support nascent proteins entering ER lumen to achieve their native conformation, mediate post-translational modification, prevent misfolded protein aggregation, and facilitate exit from the ER. Typically the role of ER chaperones expands beyond protein folding. Here, we illustrate the multifunctional nature of many ER associated molecular chaperones and folding enzymes and unique functional overlap of these proteins all designed to support the many functions of the ER membrane.

Genetic testing in monogenic early-onset atrial fibrillation.

A substantial proportion of atrial fibrillation (AF) cases cannot be explained by acquired AF risk factors. Limited guidelines exist that support routine genetic testing. We aim to determine the prevalence of likely pathogenic and pathogenic variants from AF genes with robust evidence in a well phenotyped early-onset AF population. We performed whole exome sequencing on 200 early-onset AF patients. Variants from exome sequencing in affected individuals were filtered in a multi-step process, prior to undergoing clinical classification using current ACMG/AMP guidelines. 200 AF individuals were recruited from St. Paul's Hospital and London Health Sciences Centre who were ≤ 60 years of age and without any acquired AF risk factors at the time of AF diagnosis. 94 of these AF individuals had very early-onset AF ( ≤ 45). Mean age of AF onset was 43.6 ± 9.4 years, 167 (83.5%) were male and 58 (29.0%) had a confirmed family history. There was a 3.0% diagnostic yield for identifying a likely pathogenic or pathogenic variant across AF genes with robust gene-to-disease association evidence. This study demonstrates the current diagnostic yield for identifying a monogenic cause for AF in a well-phenotyped early-onset AF cohort. Our findings suggest a potential clinical utility for offering different screening and treatment regimens in AF patients with an underlying monogenic defect. However, further work is needed to dissect the additional monogenic and polygenic determinants for patients without a genetic explanation for their AF despite the presence of specific genetic indicators such as young age of onset and/or positive family history.

Anticoagulation for Patients With Atrial Fibrillation and End-Stage Renal Disease on Dialysis: A National Survey.

Patients with atrial fibrillation (AF) have a significant increased risk of embolic stroke. Patients with end-stage renal disease who are on dialysis have an increased risk of both embolic stroke and bleeding. Stroke-prevention studies with the use of anticoagulation for AF patients have excluded patients on dialysis, so there remains no consensus on their management. We developed and implemented a pan-Canadian multidisciplinary survey to explore the current beliefs and practices concerning patients with AF on dialysis. We developed an online investigator-designed survey with both quantitative and qualitative responses with the use of a secure university-affiliated electronic service. The survey was distributed to physicians via the QxMD platform and directly to internal medicine, cardiology, and nephrology residency program directors for distribution to faculty members. 130 participants responded, including 46 cardiologists, 45 nephrologists, 30 general internists, and 9 other physicians. The preferred anticoagulant was warfarin. The CHADS2 score used to initiate anticoagulation was highly variable, with specialties differing in use of a CHADS2 threshold of ≥ 1 (P < 0.001) and the impact of previous transient ischemic attack/stroke (P = 0.02). Calciphylaxis history affected the decision to prescribe anticoagulation. Specialties differed in thresholds used to consider direct oral anticoagulants for dialysis patients, with nephrologists more likely to prescribe anticoagulation at higher CHADS2 scores. Our survey demonstrated significant heterogeneity of anticoagulation use for stroke prevention in patients with AF on dialysis. Physician specialty and patient risk profiles contributed to the observed variability. This study reemphasises the need for clinical trials, large observational studies, and consensus guidelines to address evident equipoise.