Natural history and risk factors for disease progression in early-stage hypertrophic cardiomyopathy: insights from the SOLENOID cohort

Q: What are the key findings of this study?

Early-stage functional class I hypertrophic cardiomyopathy patients had a 26% 3-year and 41% 5-year incidence of NYHA worsening or unplanned cardiovascular hospitalization.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Early-stage hypertrophic cardiomyopathy (NYHA class I) (n=961). Intervention: Baseline clinical, ECG, biomarker, and echocardiographic risk factors in early-stage HCM (e.g., atrial fibrillation, elevated NT-proBNP, COPD, older age). Primary outcome: Composite of worsening NYHA class (=N+1) and unplanned cardiovascular hospitalisation (due to sudden cardiac death, heart failure, diagnosis of atrial fibrillation, or stroke) at 3 and 5 years.

Q: What does this research mean for the field?

Early-stage NYHA class I hypertrophic cardiomyopathy patients experience substantial disease progression, with a 26% 3-year and 41% 5-year incidence of NYHA class worsening or unplanned cardiovascular hospitalization. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

William M. Bradlow; Auriane Riou; Kevin Elgui; Antoine Olivier; Valérie Ducret; Paul Trichelair; Maria Telenczuk; Félix Balazard; Philippe Chévalier; Tomás Ripoll; Pau Pericas; Marat Fudim; Manesh R. Patel; Husam M. Salah; Suresh Balu; Bradley J. Hintze; Perry Blizard; Lauren Turvey-Haigh; Emmanuelle Bégot; Aurelie Deleforge; Ninon Guichard; Alexandre Jaeger; Mariann Micsinai; Antoine Simon; Amy J. Sehnert; Maxime Touzot; Arnaud Bastien; Philippe Charron

doi:10.1136/openhrt-2026-004430

Key result

Early-stage NYHA I HCM carries a ~26% 3-year risk of functional decline or CV hospitalization.

n=961

Figures

Why the study?

Hypertrophic cardiomyopathy is a phenotypically heterogeneous disease with a wide range of clinical outcomes, motivating this investigation into the natural history and risk factors for disease progression in early-stage patients.

Key Points

To characterize the natural history of early-stage hypertrophic cardiomyopathy and evaluate clinical predictors of disease progression.
Retrospective observational cohort study (SOLENOID) conducted across five academic centers in Europe and the USA between 2010 and 2022.
Included 961 adult patients with confirmed hypertrophic cardiomyopathy in New York Heart Association (NYHA) class I, followed for a median of 4 years.
The primary endpoint was a composite of NYHA class worsening and unplanned cardiovascular hospitalization, analyzed via federated univariate Cox regression and random-effects meta-analysis.
The cumulative incidence of the composite endpoint was 26% at 3 years and 41% at 5 years, driven primarily by NYHA functional class worsening.
Strong clinical and biomarker predictors of progression included atrial fibrillation on electrocardiography (log-HR=1.56, p<0.0001), chronic obstructive pulmonary disease (log-HR=1.18, p<0.001), and elevated N-terminal pro B-type natriuretic peptide levels (log-HR=0.75, p<0.0001).
Additional significant predictors included fatigue (log-HR=0.73, p<0.01), chest pain (log-HR=0.60, p<0.05), peak A-wave velocity (log-HR=0.38, p=0.04), maximal end-diastolic left ventricular wall thickness (log-HR=0.36, p=0.04), older age (log-HR=0.33, p<0.05), and left atrial volume index (log-HR=0.29, p=0.04).

Study Design

Type

Cohort (n=961)

Multicenter

Yes

Structured PICO

P

Population

961 adults with early-stage hypertrophic cardiomyopathy in NYHA class I (mean age 54±16 years, 29% female) across five centers in Europe and the United States, followed for a median of 4 years.

O

Outcome

Composite of worsening NYHA class (=N+1) and unplanned cardiovascular hospitalisations (due to sudden cardiac death, heart failure, diagnosis of atrial fibrillation, or stroke) at 3 and 5 yearscomposite

In patients with early-stage (NYHA class I) hypertrophic cardiomyopathy, 26% experience disease progression within 3 years—primarily driven by worsening NYHA functional class—with risk predicted by age, comorbidities, symptoms, atrial fibrillation, NT-proBNP, and echocardiographic markers of diastolic load.

Limitations

Registry-derived retrospective observational design susceptible to selection, referral, and survival biases
High rates of missing data for key variables, including NT-proBNP (measured in 44%), genetic testing (missing in ~1/3), and complete echocardiography (available in ~1/3)
Baseline defined as first visit to participating center rather than actual date of HCM diagnosis, resulting in variable disease duration at inclusion
Median follow-up of 3.9–4 years is insufficient to capture long-term major adverse cardiac events in a presymptomatic population
NYHA class assessment relies partially on subjective patient self-evaluation of symptoms, which can introduce noise or bias
Retrospective observational design
Data from participating centres could not be pooled or centralised due to privacy constraints, requiring a federated meta-analysis approach
High and variable missing value rates across centres (e.g., complete echocardiographic data available for one-third of the population, NT-proBNP available for 44%, genetic testing on two-thirds)
Time of inclusion refers to the patient's first visit to the participating centre, which may not align with the original HCM diagnosis date
Small size and heterogeneity of the population across centres

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Implication

NYHA I HCM patients may need closer monitoring given progression risk; leaves open whether identified predictors guide interventions in prospective trials.

Abstract

Objectives This study aims to understand the natural history of early-stage hypertrophic cardiomyopathy (HCM) patients and identify risk factors for disease progression.Background HCM is a phenotypically heterogeneous disease, characterised by a wide range of clinical outcomes, from asymptomatic to severe heart failure.Methods The predictorS Of cLinical outcomEs iN hypertrOphIc carDiomyopathy (SOLENOID) is an observational, multicentre cohort study conducted across five centres in Europe and the USA. Inclusion criteria were patients with confirmed HCM seen between 2010 and 2022 in New York Heart Association (NYHA) class I. The study’s endpoint was a composite of worsening NYHA class (=N+1) and unplanned cardiovascular hospitalisation, assessed using Kaplan-Meier analysis. Risk factors were identified through univariate analyses at each centre, with results aggregated through meta-analysis.Results A total of 961 patients were included, with a median follow-up of 4 years. The mean age was 54±16 years and 29% of the cohort were females. 43% of patients were treated with beta-blockers and 13% had pre-existent atrial fibrillation (AF). Genetic testing revealed mutations primarily in MYBPC3 (30%) and MYH7 (13%) genes.Incidence of the composite endpoint was 26% and 41% at 3 and 5 years, respectively, with NYHA class worsening as the main contributor. The main predictors of the composite endpoint include older age (log-HR=0.33, p<0.05), chronic obstructive pulmonary disease (log-HR=1.18, p<0.001), chest pain (log-HR=0.60, p<0.05), fatigue (log-HR=0.73, p<0.01), AF on electrocardiography (log-HR=1.56, p<0.0001), higher N-terminal pro B-type natriuretic peptide levels (log-HR=0.75, p<0.0001), larger left atrial volume index (log-HR=0.29, p=0.04), peak A-wave velocity (log-HR=0.38, p=0.04) and maximal end-diastolic left ventricle wall thickness (log-HR=0.36, p=0.04).Conclusion Nearly 30% of the early-stage HCM patients experienced disease progression over 3 years, highlighting a medical unmet need. Further research is needed to determine if this population might benefit from intensive monitoring or earlier therapy.

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Cite This Study

Bradlow et al. (2026) conducted a cohort in Early-stage hypertrophic cardiomyopathy (NYHA class I) (n=961). Baseline clinical, ECG, biomarker, and echocardiographic risk factors in early-stage HCM (e.g., atrial fibrillation, elevated NT-proBNP, COPD, older age) was evaluated on Composite of worsening NYHA class (=N+1) and unplanned cardiovascular hospitalisation (due to sudden cardiac death, heart failure, diagnosis of atrial fibrillation, or stroke) at 3 and 5 years. Early-stage functional class I hypertrophic cardiomyopathy patients had a 26% 3-year and 41% 5-year incidence of NYHA worsening or unplanned cardiovascular hospitalization.

synapsesocial.com/papers/6af73ac79badce7b6084da15 https://doi.org/10.1136/openhrt-2026-004430

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Natural history and risk factors for disease progression in early-stage hypertrophic cardiomyopathy: insights from the SOLENOID cohort

Figures

Key Points

Study Design

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Natural history and risk factors for disease progression in early-stage hypertrophic cardiomyopathy: insights from the SOLENOID cohort

Figures

Key Points

Study Design

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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