The Diagnostic Utility of Holter Monitoring in Catecholaminergic Polymorphic Ventricular Tachycardia.

Background: Holter monitoring may raise suspicion of an underlying catecholaminergic polymorphic ventricular tachycardia (CPVT) diagnosis. Although not a primary investigation for CPVT, Holter monitoring is ubiquitously used as a diagnostic tool in the heart rhythm clinic.

Objectives: The objective of this study was to explore Holter monitoring in CPVT diagnosis.

Management of ultrarare inherited arrhythmia syndromes.

Ultrarare inherited arrhythmia syndromes are increasingly diagnosed as a result of increased awareness as well as increased availability and reduced cost of genetic testing. Yet by definition, their rarity and heterogeneous expression make development of evidence-based management strategies more challenging, typically employing strategies garnered from similar genetic cardiac disorders. For the most part, reliance on anecdotal experiences, expert opinion, and small retrospective cohort studies is the only means to diagnose and to treat these patients.

Impact of the method of calculating 30-day readmission rate after hospitalization for heart failure. Data from the VancOuver CoastAL Acute Heart Failure (VOCAL-AHF) registry.

Background: Thirty-day readmission rate after heart failure (HF) hospitalization is widely used to evaluate healthcare quality. Methodology may substantially influence estimated rates. We assessed the impact of different definitions on HF and all-cause readmission rates.

An international multicenter cohort study on implantable cardioverter-defibrillators for the treatment of symptomatic children with catecholaminergic polymorphic ventricular tachycardia.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) may cause sudden cardiac death (SCD) despite medical therapy. Therefore, implantable cardioverter-defibrillators (ICDs) are commonly advised. However, there is limited data on the outcomes of ICD use in children.

Novel Magnetic Resonance Imaging Tools for Hypertrophic Cardiomyopathy Risk Stratification.

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder with a well described risk of sudden cardiac death; however, risk stratification has remained a challenge. Recently, novel parameters in cardiac magnetic resonance imaging (CMR) have shown promise in helping to improve upon current risk stratification paradigms. In this manuscript, we have reviewed novel CMR risk markers and their utility in HCM.

Advances in Hypertrophic Cardiomyopathy Disease Modelling Using hiPSC-Derived Cardiomyocytes.

The advent of human induced pluripotent stem cells (hiPSCs) and their capacity to be differentiated into beating human cardiomyocytes (CMs) in vitro has revolutionized human disease modelling, genotype-phenotype predictions, and therapeutic testing. Hypertrophic cardiomyopathy (HCM) is a common inherited cardiomyopathy and the leading known cause of sudden cardiac arrest in young adults and athletes. On a molecular level, HCM is often driven by single pathogenic genetic variants, usually in sarcomeric proteins, that can alter the mechanical, electrical, signalling, and transcriptional properties of the cell.

The 2023 Canadian Cardiovascular Society Clinical Practice Update on Management of the Patient With a Prolonged QT Interval.

A prolonged QT interval on the electrocardiogram is associated with an increased risk of the torsades de pointes form of ventricular arrhythmia resulting in syncope, sudden cardiac arrest or death, or misdiagnosis as a seizure disorder. The cause of QT prolongation can be congenital and inherited as an autosomal dominant variant, or it can be transient and acquired, often because of QT-prolonging drugs or electrolyte abnormalities. Automated measurement of the QT interval can be inaccurate, especially when the baseline electrocardiogram is abnormal, and manual verification is recommended.

Mechanisms of Pathogenicity of Hypertrophic Cardiomyopathy-Associated Troponin T (TNNT2) Variant R278C During Development.

Hypertrophic cardiomyopathy (HCM) is one of the most common heritable cardiovascular diseases and variants of (cardiac troponin T) are linked to increased risk of sudden cardiac arrest despite causing limited hypertrophy. In this study, a variant, R278C, was generated in both human cardiac recombinant/reconstituted thin filaments (hcRTF) and human- induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which the R278C variant affects cardiomyocytes at the proteomic and functional levels. The results of proteomics analysis showed a significant upregulation of markers of cardiac hypertrophy and remodeling in R278C vs.

Calcium Release Deficiency Syndrome: A New Inherited Arrhythmia Syndrome.

Calcium release deficiency syndrome (CRDS) is a newly described form of inherited arrhythmia caused by damaging loss-of-function variants in the cardiac ryanodine receptor (RyR2). Unlike the prototypical RyR2 gain-of-function channelopathy, known as catecholaminergic polymorphic ventricular tachycardia, patients with CRDS are predisposed to sudden death usually in the absence of any electrical abnormalities at rest or during stress electrocardiography. This makes diagnosis incredibly challenging, however, an invasive electrophysiologic test appears to be effective in unmasking the phenotype, called the long-burst, long-pause, short-coupled ventricular extra-stimulus protocol.

Current gaps in knowledge in inherited arrhythmia syndromes.

The 3 most common inherited arrhythmia syndromes-Brugada syndrome, congenital long QT syndrome and catecholaminergic polymorphic ventricular tachycardia-were initially described in the previous century. Since then, research has evolved, which has enabled us to identify patients prior to the onset of potentially life-threatening symptoms. However, there are significant gaps in knowledge that complicate clinical management of these patients today.

RYR2-ryanodinopathies: from calcium overload to calcium deficiency.

The sarcoplasmatic reticulum (SR) cardiac ryanodine receptor/calcium release channel RyR2 is an essential regulator of cardiac excitation-contraction coupling and intracellular calcium homeostasis. Mutations of the RYR2 are the cause of rare, potentially lethal inherited arrhythmia disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) was first described more than 20 years ago and is the most common and most extensively studied cardiac ryanodinopathy.

Increased Ca Transient Underlies RyR2-Related Left Ventricular Noncompaction.

Background: A loss-of-function cardiac ryanodine receptor (RyR2) mutation, I4855M, has recently been linked to a new cardiac disorder termed RyR2 Ca release deficiency syndrome (CRDS) as well as left ventricular noncompaction (LVNC). The mechanism by which RyR2 loss-of-function causes CRDS has been extensively studied, but the mechanism underlying RyR2 loss-of-function-associated LVNC is unknown. Here, we determined the impact of a CRDS-LVNC-associated RyR2-I4855M loss-of-function mutation on cardiac structure and function.

Trigger and Substrate Mapping and Ablation for Ventricular Fibrillation in the Structurally Normal Heart.

Sudden cardiac death (SCD) represents approximately 50% of all cardiovascular mortality in the United States. The majority of SCD occurs in individuals with structural heart disease; however, around 5% of individuals have no identifiable cause on autopsy. This proportion is even higher in those <40 years old, where SCD is particularly devastating.

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

Background: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children.

Methods: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed.

Gene Therapy for Catecholaminergic Polymorphic Ventricular Tachycardia.

Over the last three decades, the genetic basis of various inherited arrhythmia syndromes has been elucidated, providing key insights into cardiomyocyte biology and various regulatory pathways associated with cellular excitation, contraction, and repolarisation. As varying techniques to manipulate genetic sequence, gene expression, and different cellular pathways have become increasingly defined and understood, the potential to apply various gene-based therapies to inherited arrhythmia has been explored. The promise of gene therapy has generated significant interest in the medical and lay press, providing hope for sufferers of seemingly incurable disorders to imagine a future without repeated medical intervention, and, in the case of various cardiac disorders, without the risk of sudden death.

Population Prevalence of Premature Truncating Variants in Plakophilin-2 and Association With Arrhythmogenic Right Ventricular Cardiomyopathy: A UK Biobank Analysis.

Background: Truncating variants in the desmosomal gene tv) cause arrhythmogenic right ventricular cardiomyopathy (ARVC) yet display varied penetrance and expressivity.

Methods: We identified individuals with tv from the UK Biobank (UKB) and determined the prevalence of an ARVC phenotype and other cardiovascular traits based on clinical and procedural data. The tv minor allelic frequency in the UKB was compared with a second cohort of probands with a clinical diagnosis of ARVC (ARVC cohort), with a figure of 1:5000 assumed for disease prevalence.

The design and rationale of the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study.

Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). Despite being the most common inherited cardiovascular disorder, it is still highly underdiagnosed and undertreated worldwide. We designed the Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study to test the hypothesis that opportunistic genetic testing for FH among patients hospitalized for acute coronary syndrome (ACS) will increase the diagnosis of FH and improve patient outcomes.