Novel risk predictor of arrhythmias for patients with potassium channel-related congenital long QT syndrome.

Background: Congenital long QT syndrome (LQTS) is characterized by delayed ventricular repolarization, predisposing to potentially lethal ventricular arrhythmias. The variability in disease severity among patients remains largely unexplored, underscoring the limitations of current risk stratification methods.

Objective: We aimed to evaluate the potential utility of electrocardiographic markers from the exercise stress test (EST) in identifying patients with high-risk LQTS.

Unexplained sudden cardiac arrest and sudden cardiac death in the young: What is killing these young people when nothing is found?

Unexplained sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in the young remains a critical issue for clinicians, researchers, patients and their family members. In this review, we explore the current status of SCA and SCD evaluation in the young, including recent monogenic and polygenic disease discoveries, advancements in cardiac imaging and our growing understanding of the role of the Purkinje system in triggering life threatening and even fatal ventricular arrhythmias. Yet, despite these advancements, over a third of SCA and SCD among individuals with seemingly structurally normal hearts remain unexplained.

Prevalence, Penetrance, and Phenotypic Manifestation of Cardiomyopathy-Associated Genetic Variants in the General Population: Insights from a Mayo Clinic Biobank Study.

Objective: To determine the prevalence, penetrance, and disease expression of cardiomyopathy-related genetic variants in an unselected, richly phenotyped Mayo Clinic population in the setting of preemptive sequencing, with return of incidental findings following the American College of Medical Genetics and Genomics recommendations.

Patients And Methods: We analyzed a quaternary medical center-based biobank cohort (n=983) for reportable variants in 15 cardiomyopathy genes. Prioritization of genetic variants was performed using an internally developed pipeline to identify potentially reportable variants.

Multiplexed Assays of Variant Effect and Automated Patch Clamping Improve -LQTS Variant Classification and Cardiac Event Risk Stratification.

Background: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance.

The impact of mavacamten dosing on wall thickness regression: an insight from longer term follow-up based on genetic profile.

Introduction: We have previously reported that genetically positive patients have a more profound early decrease in provocable left ventricular outflow tract gradient compared to genetically negative patients utilizing mavacamten in the first 12 weeks of therapy.

Methods And Results: In this current analysis, we found that genetically positive patients have less favorable remodeling as measured by left ventricular wall thickness regression when evaluated long-term as compared to genetically negative patients, despite an overall better early response to mavacamten. The majority of genetically positive patients were maintained on only 2.

Sudden cardiac arrest occurring in temporal proximity to consumption of energy drinks.

Background: Energy drinks potentially can trigger life-threatening cardiac arrhythmias. It has been postulated that the highly stimulating and unregulated ingredients alter heart rate, blood pressure, cardiac contractility, and cardiac repolarization in a potentially proarrhythmic manner.

Objective: The purpose of this study was to describe our experience regarding sudden cardiac arrest (SCA) occurring in proximity to energy drink consumption in patients with underlying genetic heart diseases.

Arrhythmic manifestations and outcomes of definite and probable cardiac sarcoidosis.

Background: The 2014 Heart Rhythm Society consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes.

Objective: The purpose of this study was to evaluate the electrophysiological/arrhythmic phenotype and outcomes of patients with definite and probable CS.

Methods: We analyzed the arrhythmic/electrophysiological phenotype in a single-center North American cohort of 388 patients (median age 56 years; 39% female, n = 151) diagnosed with definite (n = 58) or probable (n = 330) CS (2000-2022).

State of Gene Therapy for Monogenic Cardiovascular Diseases.

Over the past 2 decades, significant efforts have been made to advance gene therapy into clinical practice. Although successful examples exist in other fields, gene therapy for the treatment of monogenic cardiovascular diseases lags behind. In this review, we (1) highlight a brief history of gene therapy, (2) distinguish between gene silencing, gene replacement, and gene editing technologies, (3) discuss vector modalities used in the field with a special focus on adeno-associated viruses, (4) provide examples of gene therapy approaches in cardiomyopathies, channelopathies, and familial hypercholesterolemia, and (5) present current challenges and limitations in the gene therapy field.

Artificial intelligence-enhanced electrocardiogram for arrhythmogenic right ventricular cardiomyopathy detection.

Aims: ECG abnormalities are often the first signs of arrhythmogenic right ventricular cardiomyopathy (ARVC) and we hypothesized that an artificial intelligence (AI)-enhanced ECG could help identify patients with ARVC and serve as a valuable disease-detection tool.

Methods And Results: We created a convolutional neural network to detect ARVC using a 12-lead ECG. All patients with ARVC who met the 2010 task force criteria and had disease-causative genetic variants were included.

Imaging of Cardiac Sarcoidosis: An Update and Future Aspects.

Cardiac sarcoidosis (CS), an increasingly recognized disease of unknown etiology, is associated with significant morbidity and mortality. Given the limited diagnostic yield of traditional endomyocardial biopsy (EMB), there is increasing reliance on multimodality cardiovascular imaging in the diagnosis and management of CS, with EMB being largely supplanted by the use of F-fluorodeoxyglucose (FDG-PET) and cardiac magnetic resonance imaging (CMR). This article aims to provide a comprehensive review of imaging modalities currently utilized in the screening, diagnosis, and monitoring of CS, while highlighting the latest developments in each area.

A Multi-Omics Atlas of Sex-Specific Differences in Obstructive Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease. Women with HCM tend to have a later onset but more severe disease course. However, the underlying pathobiological mechanisms for these differences remain unknown.