William J. McKenna

Cardiomyopathy and Myosin Studies

University College London

About

Research focus

Cardiomyopathy and Myosin Studies

Impact

2,405 pubs · 109,885 cites · h-index 165

Affiliations

Publications

JACCMurphy et al.cohort

Among 45 PRKAG2 gene carriers, survival was 91% at a mean follow-up of 12.2 years, with 78% of adults exhibiting left ventricular hypertrophy and 38% requiring pacemaker implantation for progressive conduction disease at a mean age of 38 years.

AMP kinase (PRKAG2) disease is an uncommon cause of hypertrophic cardiomyopathy characterized by 100% ECG penetrance by age 18, progressive conduction disease frequently requiring permanent pacing, and extracardiac skeletal myopathy.

JACCKubo et al.cohort

Restrictive phenotype in HCM is linked to ~56% 5-year event-free survival.

May inform HCM risk stratification; extends genetic-phenotypic links but leaves management implications open pending prospective data.

JACCPurevjav et al.preclinical

Mutant human nebulette variants drive severe LV dilation and heart failure in mice.

Identifies NEBL as a novel susceptibility gene for endocardial fibroelastosis and dilated cardiomyopathy.

Hunain Shiwani

Cardiac Imaging · St Bartholomew's Hospital

The 15mm threshold for diagnosing HCM was established in 1973 using M-mode echocardiography and just 79 control patients. Today, with access to large-scale datasets and AI capabilities, we can finally re-examine these decades-old assumptions. Our study analyzed more than 50,000 cardiac MRIs using AI to make precise measurements at a scale never before possible. A measurement that would be concerning in a small-framed young woman might be perfectly normal for a tall, older man.

A More Accurate Diagnosis of Hypertrophic Cardiomyopathy

Journal of the American College of CardiologyMcKenna et al.Jan 2025

Revista Española de Cardiología (English Edition)Serrano et al.cohort

MYBPC3 p.Arg891Alafs*160 founder variant shows incomplete penetrance, causing HCM in ~57% of carriers.

Supports cautious genetic counseling for carriers; leaves open whether lower event rates generalize beyond this founder population.

JACCLinde et al.RCT

Biventricular pacing increases walking distance by ~20% at 12 months in heart failure.

Biventricular pacing provides sustained improvements in functional capacity, quality of life, and left ventricular function over 12 months in patients with NYHA class III heart failure and intraventricular conduction delay.

JACCMestroni et al.Cohort Study

Familial DCM features younger age and higher EF versus sporadic cases, being ~56% autosomal dominant.

Clinical review reveals genetic mechanisms and phenotypic heterogeneity in familial dilated cardiomyopathy, highlighting the importance of family screening.

JACCCrilley et al.Original Research

Sarcomeric HCM mutations are linked to a ~30% lower cardiac phosphocreatine to ATP ratio.

Observational study demonstrates reduced myocardial energy status across sarcomeric mutation carriers, indicating that metabolic impairment precedes cardiac hypertrophy.

JACCCorrado et al.case_series

Left ventricular involvement was found in 76% (32/42) of hearts with ARVC, was age-dependent, and was associated with clinical arrhythmic events, more severe cardiomegaly, inflammatory infiltrates, and heart failure.

ARVC frequently involves the left ventricle (76% of cases), which is associated with older age, arrhythmias, and heart failure, indicating it is a progressive disease not isolated to the right ventricle.

JACCO’Hanlon et al.Prognostic Study

CMR-detected myocardial fibrosis in HCM linked to ~240% greater risk of major clinical events.

Cohort study reveals higher risk of adverse cardiac events in hypertrophic cardiomyopathy patients with fibrosis, highlighting late gadolinium enhancement for risk stratification.

JACCElliott et al.cohort

Prior VT/VF in HCM is linked to 59% 5-year survival without death or ICD discharge.

In HCM patients surviving VT/VF, recurrent events are common, and ICD therapy appears to offer the best potential benefit for survival.

EHJLorenzoni et al.cross-sectional

Syncope or NSVT in HCM patients shows no association with worse coronary vasodilator reserve.

Does not support coronary vasodilator reserve as a determinant of syncope or NSVT in hypertrophic cardiomyopathy; leaves open other contributors to sudden death risk.

JACCSharma et al.Original Research

Metabolic exercise testing revealed higher exercise capacity in elite athletes with physiologic LVH compared to athletes with HCM.

May aid differentiation of cardiac conditions in athletes; leaves open larger validation before practice change.

EHJFinocchiaro et al.review

Personalized medicine complements evidence-based care to optimize management of heart failure and inherited cardiomyopathies.

May inform genotype-guided risk stratification in cardiomyopathies; leaves open prospective trials validating personalized integration with evidence-based care.

CirculationRichardson et al.Original Research

Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies

Jeffrey Towbin

Pediatric / Congenital Cardiology · St. Jude Children's Research Hospital

3mo

Our study indicates that variants in ANKRD1 result in dysfunction of the contraction apparatus and signaling machinery of the heart – the method by which cells communicate to influence heart function. This clarifies the mechanisms by which these inherited mutations cause disease in a subset of DCM patients.

ANKRD1, the Gene Encoding Cardiac Ankyrin Repeat Protein, Is a Novel Dilated Cardiomyopathy Gene

Journal of the American College of CardiologyMoulik et al.Jul 2009

JACCGigli et al.cohort

Desmosomal and LMNA gene variants identify the subset of dilated cardiomyopathy patients at greatest risk for sudden cardiac death and life-threatening ventricular arrhythmias, regardless of left ventricular ejection fraction.

May refine arrhythmic risk stratification in DCM beyond LVEF; leaves open whether genotype guides ICD decisions.

JACCSen‐Chowdhry et al.Cohort Study

Left-dominant arrhythmogenic cardiomyopathy presents with arrhythmia or chest pain and carries a ~50% misdiagnosis rate.

May inform fibrosis-based risk stratification in left-dominant arrhythmogenic cardiomyopathy; leaves open need for prospective validation before practice change.

JACCMaron et al.Risk Assessment

American College of Cardiology/European Society of Cardiology Clinical Expert Consensus Document on Hypertrophic Cardiomyopathy

JACCVatta et al.cross-sectional

Cypher/ZASP mutations are identified in 6% of LV dysfunction cases and linked to DCM and LVNC.

Cypher/ZASP variants may refine genetic counseling in DCM families; leaves open causality and screening utility in non-compaction.

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