Is There a Sex Difference in the Prognosis of Hypertrophic Cardiomyopathy? A Systematic Review and Meta-Analysis

Abstract

Background It is still unclear whether there is a sex difference in the prognosis of patients with hypertrophic cardiomyopathy (HCM). Therefore, we performed a meta-analysis to elucidate the association between sex and adverse outcomes in patients with HCM. Methods and Results The PubMed, Cochrane Library, and Embase databases were used to search for studies on sex differences in prognosis in patients with HCM up to August 17, 2021. Summary effect sizes were calculated using a random effects model. The protocol was registered in PROSPERO (International prospective register of systematic reviews) (registration number- CRD42021262053). A total of 27 cohorts involving 42 365 patients with HCM were included. Compared with male subjects, female subjects had a higher age at onset (mean difference=5.61 [95% CI, 4.03-7.19]), a higher left ventricular ejection fraction (standard mean difference=0.09 [95% CI, 0.02-0.15]) and a higher left ventricular outflow tract gradient (standard mean difference=0.23 [95% CI, 0.18-0.29]). The results showed that compared with male subjects with HCM, female subjects had higher risks of HCM-related events (risk ratio [RR]=1.61 [95% CI, 1.33-1.94], I²=49%), major cardiovascular events (RR=3.59 [95% CI, 2.26-5.71], I²=0%), HCM-related death (RR=1.57 [95% CI, 1.34-1.82], I²=0%), cardiovascular death (RR=1.55 [95% CI, 1.05-2.28], I²=58%), noncardiovascular death (RR=1.77 [95% CI, 1.46-2.13], I²=0%) and all-cause mortality (RR=1.43 [95% CI, 1.09-1.87], I²=95%), but not atrial fibrillation (RR=1.13 [95% CI, 0.95-1.35], I²=5%), ventricular arrhythmia (RR=0.88 [95% CI, 0.71-1.10], I²=0%), sudden cardiac death (RR=1.04 [95% CI, 0.75-1.42], I²=38%) or composite end point (RR=1.24 [95% CI, 0.96-1.60], I²=85%). Conclusions Based on current evidence, our results show significant sex-specific differences in the prognosis of HCM. Future guidelines may emphasize the use of a sex-specific risk assessment for the diagnosis and management of HCM.

Keywords: hypertrophic cardiomyopathy; meta‐analysis; prognosis; sex.

Figure 1. Flowchart of study selection in the systematic review and meta‐analysis of sex difference in the prognosis of hypertrophic cardiomyopathy.

Other sources include the American College of Cardiology website and Circulation website. HCM indicates hypertrophic cardiomyopathy.

Figure 2. Forest plot showing the differences in age and cardiac function at diagnosis between sexes in patients with hypertrophic cardiomyopathy.

A, Diagnosis age in women and men with hypertrophic cardiomyopathy; B, Left ventricular ejection fraction in women and men with hypertrophic cardiomyopathy; C, Left ventricular outflow tract gradient in women and men with hypertrophic cardiomyopathy. HCM indicates hypertrophic cardiomyopathy; LVEF, left ventricular ejection fraction; and LVOT, left ventricular outflow tract.

Figure 3. Forest plot for the association between sex and cardiovascular diseases in patients with hypertrophic cardiomyopathy.

A, Forest plot for the association between sex and atrial fibrillation in patients with HCM; B, Forest plot for the association between sex and ventricular arrhythmia in patients with HCM; C, Forest plot for the association between sex and HCM‐related events in patients with HCM; D, Forest plot for the association between sex and major cardiovascular events in patients with HCM. AF indicates atrial fibrillation; and HCM, hypertrophic cardiomyopathy.

Figure 4. Forest plot for the association between sex and death or composite end point in patients with hypertrophic cardiomyopathy.

A, Forest plot for the association between sex and sudden cardiac death in patients with HCM; B, Forest plot for the association between sex and HCM‐related death in patients with HCM; C, Forest plot for the association between sex and cardiovascular death in patients with HCM; D, Forest plot for the association between sex and noncardiac death in patients with HCM; E, Forest plot for the association between sex and all‐cause mortality in HCM; F, Forest plot for the association between sex and composite end point in patients with HCM. HCM indicates hypertrophic cardiomyopathy; and SCD, sudden cardiac death.