Sex Differences in Characteristics and Outcomes Among Patients With Hypertrophic Cardiomyopathy: Insights From the REVEAL‐HCM Study

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Hypertrophic cardiomyopathy (n=3247). Intervention: Female sex vs. Male sex. Primary outcome: Cardiovascular death (HR 1.37, 95% CI 1.02-1.82, p=0.03).

Q: What does this research mean for the field?

Female sex is associated with a 37% higher risk of cardiovascular death in hypertrophic cardiomyopathy, but this excess risk is largely explained by older age, more advanced symptoms, greater indexed wall thickness, and phenotypic differences. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Masayuki Nakamura; Haruhiko Abe; Yasunori Ueda; Hiroaki Kitaoka; Yasushi Sakata; Kaoru Dohi; Yukichi Tokita; Takao Kato; Shouji Matsushima; Masashi Amano; Takeshi Kitai; Atsushi Okada; Yutaka Furukawa; Toshihiro Tamura; Akihiro Hayashida; Kenji Andò; Satoshi Yuda; Moriaki Inoko; Kazushige Kadota; Yukio Abe; Katsuomi Iwakura; Tetsuya Kitamura; Jun Masuda; Takahiro Ohara; Takashi Omura; Takashi Tanigawa; K Nakamura; Kiyomasa Nakatsuka; Kunihiro Nishimura; Chisato Izumi; the ESCAPE‐NEXT Investigators

doi:10.1161/jaha.125.046708

Figures

Key Points

To clarify sex-based differences in baseline clinical features and determine factors contributing to cardiovascular death among patients with hypertrophic cardiomyopathy.
Multicenter, retrospective observational study (REVEAL-HCM registry, UMIN000046932) conducted in Japan between January 1, 2006, and December 31, 2018.
Included 3247 patients aged ≥16 years with hypertrophic cardiomyopathy (median age 67 years; 43% women; median follow-up of 6.8 years in men and 5.9 years in women).
Assessed baseline clinical characteristics, morphological phenotypes, and cardiovascular mortality using univariable and multivariable Cox proportional hazards models.
Women were significantly older at presentation, presented with more severe symptoms (52% NYHA class II–IV versus 35% in men), and experienced a higher risk of cardiovascular death (HR, 1.37 [95% CI, 1.02–1.82]; P=0.03).
In multivariable analysis, cardiovascular death was independently associated with older age (per 1-year increase; HR, 1.04 [95% CI, 1.02–1.06]), advanced NYHA class (HR, 1.99 [95% CI, 1.40–2.82]), history of atrial fibrillation (HR, 1.55 [95% CI, 1.10–2.18]), greater maximal wall thickness indexed to body surface area (per 1-mm/m2 increase; HR, 1.12 [95% CI, 1.06–1.20]), and apical HCM (HR, 0.53 [95% CI, 0.32–0.88]).
Adjustment for these clinical, structural, and phenotypic variables attenuated the excess hazard of cardiovascular death observed in female patients.

Study Design

Type

Observational (n=3,247)

Multicenter

Yes

Structured PICO

P

Population

3,247 adults (median age 67, 43.7% female) with hypertrophic cardiomyopathy followed for a median of 5.9 to 6.8 years.

O

Outcome

Cardiovascular death, including sudden cardiac death, death from heart failure, ventricular arrhythmic events, stroke, and thrombosishard clinical

Main Result

Hazard Ratio: 1.37 (95% CI 1.02–1.82)

p-value: p=0.03

Limitations

Retrospective observational design limiting definitive causal relationships
Absence of genetic testing precluding assessment of genotype‐sex interactions
High proportion of missing data in the multivariable analysis
Potential underestimation of sudden cardiac death as patients who died before a definitive diagnosis were not captured
Heterogeneity in enrollment profiles reflecting social determinants such as disparities in health care access
Retrospective observational study design
Potential time gap between actual date of HCM diagnosis and the date of study enrollment
High rate of missing data for the multivariable analysis (21.2%), requiring complete case analysis

Implication

The elevated risk of cardiovascular death previously observed in female patients with hypertrophic cardiomyopathy is primarily driven by their older age at presentation, more advanced symptoms, greater body size-adjusted wall thickness, and a lower prevalence of the more benign apical HCM phenotype.

Abstract

Background Female sex has been associated with poor prognosis in hypertrophic cardiomyopathy (HCM), but the factors contributing to this disparity remain insufficiently defined. We aimed to clarify sex differences in clinical characteristics and factors associated with cardiovascular death in Japan. Methods This multicenter, retrospective observational study of HCM was conducted between January 1, 2006, and December 31, 2018 (REVEAL‐HCM study [Multicenter Registry to Evaluate Risk Factors for Disease Progression, Sudden Cardiac Death and Adverse Clinical Outcomes in Japanese Patients With Hypertrophic Cardiomyopathy]; UMIN000046932). Patients aged ≥16 years with HCM were enrolled. Baseline characteristics and clinical outcomes including cardiovascular death were assessed. Univariable and multivariable Cox proportional hazards models were used to identify factors associated with cardiovascular death. Results Of 3247 patients (median age, 67 years; 43% women), women were older and more symptomatic at presentation (52% New York Heart Association class II–IV versus 35% in men). Cardiovascular death was more common in women (hazard ratio [HR], 1.37 [95% CI, 1.02–1.82]; P =0.03). In multivariable analysis, older age (per 1‐year increase; HR, 1.04 [95% CI, 1.02–1.06]), advanced New York Heart Association class (HR, 1.99 [95% CI, 1.40–2.82]), history of atrial fibrillation (HR, 1.55 [95% CI, 1.10–2.18]), greater maximal wall thickness indexed to body surface area (per 1‐mm/m 2 increase; HR, 1.12 [95% CI, 1.06–1.20]), and apical HCM (HR, 0.53 [95% CI, 0.32–0.88]) were independently associated with cardiovascular death, attenuating the HR for female sex. Conclusions Sex differences in clinical characteristics and outcomes were observed. The excess cardiovascular death in women with HCM was largely explained by older age, more advanced symptoms, greater indexed wall thickness, and sex‐specific differences in both the prevalence and prognostic impact of apical HCM.

Discussion

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Cite This Study

Nakamura et al. (2026) conducted an observational in Hypertrophic cardiomyopathy (n=3,247). Female sex vs. Male sex was evaluated on Cardiovascular death (HR 1.37, 95% CI 1.02-1.82, p=0.03).

synapsesocial.com/papers/6a3c2319d15afadd906f9d16 https://doi.org/10.1161/jaha.125.046708

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Sex Differences in Characteristics and Outcomes Among Patients With Hypertrophic Cardiomyopathy: Insights From the REVEAL‐HCM Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Sex Differences in Characteristics and Outcomes Among Patients With Hypertrophic Cardiomyopathy: Insights From the REVEAL‐HCM Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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