Artificial Intelligence-Enhanced Electrocardiography for Prediction of Incident Hypertension.

Importance: Hypertension underpins significant global morbidity and mortality. Early lifestyle intervention and treatment are effective in reducing adverse outcomes. Artificial intelligence-enhanced electrocardiography (AI-ECG) has been shown to identify a broad spectrum of subclinical disease and may be useful for predicting incident hypertension.

Influence of age and sex on the diagnostic yield of inherited cardiac conditions in sudden arrhythmic death syndrome decedents.

Aims: Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).

Methods And Results: Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included.

The Clinical Trajectory of NYHA Functional Class I Patients With Obstructive Hypertrophic Cardiomyopathy.

Background: An improved understanding of the natural history in NYHA functional class I patients with obstructive hypertrophic cardiomyopathy (oHCM) is needed.

Objectives: Using a multicenter registry (SHaRe [Sarcomeric Human Cardiomyopathy Registry]), this study described the natural history in patients with oHCM who were classified as NYHA functional class I at the initial visit compared with patients classified as NYHA functional class II and reported baseline characteristics associated with incident clinical events.

Methods: Incident events assessed included a composite of NYHA functional class III to IV symptoms, left ventricular ejection fraction <50%, atrial fibrillation, stroke, ventricular arrhythmias, septal reduction therapy, ventricular assist device or transplantation, or death.

Cardiomyopathies in 100,000 genomes project: interval evaluation improves diagnostic yield and informs strategies for ongoing gene discovery.

Background: Cardiomyopathies are clinically important conditions, with a strong genetic component. National genomic initiatives such as 100,000 Genome Project (100KGP) provide opportunity to study these rare conditions at scale beyond conventional research studies.

Methods: We present the clinical and molecular characteristics of the 100KGP cohort, comparing paediatric and adult probands with diverse cardiomyopathies.

Association between coronary microvascular dysfunction and exercise capacity in dilated cardiomyopathy.

Background: Aerobic exercise capacity is an independent predictor of mortality in dilated cardiomyopathy (DCM), but the central mechanisms contributing to exercise intolerance in DCM are unknown. The aim of this study was to characterize coronary microvascular function in DCM and determine if cardiovascular magnetic resonance (CMR) measures are associated with aerobic exercise capacity.

Methods: Prospective case-control comparison of adults with DCM and matched controls.

Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard-of-care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in-depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype-first screening of asymptomatic individuals for Mendelian CVD.

Long-term follow-up of the TRED-HF trial: Implications for therapy in patients with dilated cardiomyopathy and heart failure remission.

Aims: In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short term after therapy withdrawal. This follow-up investigates the longer-term effects of therapy withdrawal.

Methods And Results: TRED-HF was a randomized trial investigating heart failure therapy withdrawal in patients with recovered DCM over 6 months.

Reproductive options and genetic testing for patients with an inherited cardiac disease.

In the past decade, genetic testing for cardiac disease has become part of routine clinical care. A genetic diagnosis provides the possibility to clarify risk for relatives. For family planning, a genetic diagnosis provides reproductive options, including prenatal diagnosis and preimplantation genetic testing, that can prevent an affected parent from having a child with the genetic predisposition.

Arrhythmic Risk Stratification by Cardiovascular Magnetic Resonance Imaging in Patients With Nonischemic Cardiomyopathy.

Background: Myocardial fibrosis (MF) forms part of the arrhythmic substrate for ventricular arrhythmias (VAs).

Objectives: This study sought to determine whether total myocardial fibrosis (TF) and gray zone fibrosis (GZF), assessed using cardiovascular magnetic resonance, are better than left ventricular ejection fraction (LVEF) in predicting ventricular arrhythmias in patients with nonischemic cardiomyopathy (NICM).

Methods: Patients with NICM in a derivation cohort (n = 866) and a validation cohort (n = 848) underwent quantification of TF and GZF.

Precision prediction of heart failure events in patients with dilated cardiomyopathy and mildly reduced ejection fraction using multi-parametric cardiovascular magnetic resonance.

Aims: To assess whether left ventricular (LV) global longitudinal strain (GLS), derived from cardiovascular magnetic resonance (CMR), is associated with (i) progressive heart failure (HF), and (ii) sudden cardiac death (SCD) in patients with dilated cardiomyopathy with mildly reduced ejection fraction (DCMmrEF).

Methods And Results: We conducted a prospective observational cohort study of patients with DCM and LV ejection fraction (LVEF) ≥40% assessed by CMR, including feature-tracking to assess LV GLS and late gadolinium enhancement (LGE). Long-term adjudicated follow-up included (i) HF hospitalization, LV assist device implantation or HF death, and (ii) SCD or aborted SCD (aSCD).

ClinGen Hereditary Cardiovascular Disease Gene Curation Expert Panel: Reappraisal of Genes associated with Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ~1 in 500 and exhibits marked genetic heterogeneity. Previously published in 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity. Here we report work by the ClinGen Hereditary Cardiovascular Disorders Gene Curation Expert Panel (HCVD-GCEP) to reappraise the clinical validity of previously curated and new putative HCM genes.

Guidance for estimating penetrance of monogenic disease-causing variants in population cohorts.

Penetrance is the probability that an individual with a pathogenic genetic variant develops a specific disease. Knowing the penetrance of variants for monogenic disorders is important for counseling of individuals. Until recently, estimates of penetrance have largely relied on affected individuals and their at-risk family members being clinically referred for genetic testing, a 'phenotype-first' approach.

Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery.

Background: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as "genetic constraint".