William J. McKenna

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.

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.

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.

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.

JUL 2002LindeJournal of the American College of Cardiology

Biventricular pacing increases 6-minute walk 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.

JUL 1999MestroniJournal of the American College of Cardiology

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.

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.

NOV 1997CorradoJournal of the American College of Cardiology

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.

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.

MAY 1999ElliottJournal of the American College of Cardiology

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.

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.

SEP 2000SharmaJournal of the American College of Cardiology

Metabolic exercise testing revealed significantly higher peak oxygen consumption in elite athletes with physiologic LVH compared to athletes with HCM (66.2 vs 34.3 ml/kg/min; p<0.0001).

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

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.

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

SEP 2019GigliJournal of the American College of Cardiology

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.

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.

NOV 2003MaronJournal of the American College of Cardiology

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

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.