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July 1, 2026Journal of the American College of Cardiology
Natural History of Asymptomatic Phenotypically Mild HCM
Constantin‐Cristian TopriceanuIswaree Devi BalakrishnanChristoffer Rasmus VissingAnna Axelsson RajaV ParikhPeter-Paul ZwetslootMichelle MichelsAlessia ArgiroNiccolò MauriziJohn C. StendahlR LampertJulia E. MarineJames S. WareJoseph W. RossanoA T OwensKimberly Y. LinThomas D. RyanDominic AbramsJodie InglesBelinda GrayJ MoonGabriella CapturL CrottiSara SaberiAdam S. HelmsS M DayIacopo OlivottoHenning BundgaardN K LakdawalaCarolyn Y. Ho
Key result
Progression to NYHA ≥II in mild HCM is linked to ~179% higher MACE risk.
- HR 2.79
- 95% CI 2.30-3.39
- n=2,500
Journal of the American College of Cardiology published a graphical abstract
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Why the study?
Little is known about the natural history and predictors of major adverse cardiovascular events in patients with phenotypically mild HCM.
Key Points
- This research aims to examine the progression and outcomes of individuals with phenotypically mild hypertrophic cardiomyopathy (HCM) who are asymptomatic.
- Study design evaluated asymptomatic individuals diagnosed with mild HCM.
- Assessments included genetic screening and regular cardiac function monitoring.
- Follow-up evaluations tracked changes over a defined period.
- Significant proportion of individuals experienced deterioration in cardiac function over time.
- Genetic factors were identified as potential predictors for progression.
- Monitoring revealed critical thresholds for intervention based on cardiac performance.
Study Design
Type
Cohort (n=2,500)
PICO
P
Population
2,500 patients with phenotypically mild hypertrophic cardiomyopathy, free of prior MACE and in NYHA class I, followed for a mean of 7 years.
E
Exposure / Comparator
Progression to NYHA class ≥II symptoms vs Remaining in NYHA class I
O
Primary Outcome
Major adverse cardiovascular events (MACE) — HR 2.79 (2.30-3.39)
Main Result
Hazard Ratio: 2.79 (95% CI 2.3–3.39)
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“These patients are at higher risk for adverse events in the medium term, and therefore may both receive the greatest benefit from treatment and be able to demonstrate response to therapy.”
DMDr. Michael W. Russell
“Future work could develop these data into a risk calculator for clinical progression of disease, similar to the highly beneficial and widely adopted sudden cardiac death-risk calculators in HCM, which will help guide clinical monitoring and treatment.”
Implication
May support closer monitoring in mild asymptomatic HCM; hypothesis-generating for genetic predictors pending prospective validation.
Abstract
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Cite This Study
Topriceanu et al. (2026) conducted a cohort in Phenotypically mild hypertrophic cardiomyopathy (n=2,500). Progression to NYHA class ≥II symptoms vs. Remaining in NYHA class I was evaluated on Major adverse cardiovascular events (MACE) (HR 2.79, 95% CI 2.30-3.39). Progression from NYHA class I to ≥II symptoms in patients with phenotypically mild HCM was associated with a significantly increased risk of MACE (HR 2.79; 95% CI 2.30-3.39).