Female Patients with HCM Experience Worse Outcomes, Greater Symptom Burden

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New research is shedding light on sex-based differences in outcomes among patients with hypertrophic cardiomyopathy (HCM).

A systematic review and meta-analysis of nearly 30 observational studies with more than 44,000 patients with HCM, results of the study offered insight into significant differences in disease characteristics between male and female patients as well as an increased risk of all-cause mortality and increased likelihood of carrying the myosin heavy chain beta 7 mutation among female patients compared to their male counterparts.¹

“The primary observations of this study indicate that female individuals with HCM exhibit a heightened risk of adverse events, specifically all-cause mortality and composite endpoint outcomes, when compared to their male counterparts,” wrote investigators.¹ “However, intriguingly, no statistically significant disparity was detected in the occurrence of arrhythmic endpoints between the 2 sex groups.”

An autosomal dominant disease caused by a mutation in sarcomere protein genes that affect heart contraction, contemporary estimates from echocardiographic studies suggest the overall prevalence of HCM to be about 1 in 500 adults. Despite HCM being more common among male patients, females with HCM are typically diagnosed at an older age and exhibit a greater symptom burden.^1,2

In the current study, a trio of investigators from the Department of Cardiology at Chengdu Fifth People's Hospital in China sought to provide a comprehensive overview of the differences in clinical outcomes between female and male patients with HCM. With this in mind, investigators designed their study as a systematic review and meta-analysis of observational studies published within the PubMed, Embase, Cochrane Library, and Web of Science databases from inception through June 2023.¹

Investigators identified 3 primary endpoints of interest for their research endeavor. These endpoints of interest were defined as all-cause mortality, an arrhythmic endpoint comprising sudden cardiac death (SCD), sustained ventricular tachycardia, ventricular fibrillation, or aborted SCD, and a composite endpoint incorporating either of the first 2 endpoints plus hospitalization for heart failure or cardiac transplantation. Investigators pointed out a random-effects meta-analysis model was used to determine pooled estimates for each outcome.¹

Overall, 3612 records underwent screening for inclusion in the systematic review and meta-analysis. Of these, 29 observational studies were deemed eligible for inclusion in the review. These studies were conducted between 2004 and 2022 and included 44,677 patients with HCM. Among this cohort, 16,807 were female and 27,870 were male. Investigators pointed out the mean age of the patients ranged from 44.9 to 63.0 years and the follow-up duration ranged from 30 days to 18.1 years.¹

Upon analysis of baseline characteristics, results indicated female patients presented at a more advanced age (55.66±0.04 years vs 50.38±0.03 years; pooled mean difference [MD], 0.31; 95% Confidence interval [CI], 0.22–0.40; P= .000, I2 = 88.89%], with a greater proportion of New York Heart Association class III/IV patients (pooled odds ratio [OR], 1.94; 95% CI, 1.55–2.43; P=.000, I2 = 85.92%), and with a greater prevalence of left ventricular outflow tract gradient greater than or equal to 30 mmHg (pooled OR, 1.48; 95% CI, 1.27–1.73; P=.000, I2 = 68.88%) relative to male patients with HCM. Investigators also highlighted females with HCM were more likely to have a positive genetic test (pooled OR, 1.27; 95% CI, 1.08–1.48; P=.000, I2 = 42.74%) and to carry the myosin heavy chain beta 7 mutation (pooled OR, 1.26; 95% CI, 1.04–1.54; P=.020, I2 = 0.00%) relative to their male counterparts.¹

In the primary endpoint analyses, results suggested female sex was associated with a significant increase in risk of all-cause mortality (pooled OR , 1.62; 95% CI, 1.38–1.89, P=.000, I2 = 72.78%) and the composite endpoint (pooled OR, 1.47; 95% CI, 1.20–1.79; P=.000, I2 = 84.96%), but there was no substantial difference observed for the arrhythmic endpoint (pooled OR, 1.08; 95% CI, 0.87–1.34; P=.490, I2 = 55.48%).¹

“Traditionally, heart disease has been predominantly perceived as a condition affecting men, highlighting longstanding disparities in healthcare that persist to this day and have been further underscored by the COVID-19 pandemic,” investigators added.¹ “Consequently, it is imperative to critically reevaluate disease definitions and enhance awareness to mitigate delays in the diagnosis and treatment of HCM in women, thereby fostering equitable healthcare practices.”

References:

1. Liu G, Su L, Lang M. A systematic review and meta-analysis of sex differences in clinical outcomes of hypertrophic cardiomyopathy. Front Cardiovasc Med. 2023;10:1252266. Published 2023 Dec 5. doi:10.3389/fcvm.2023.1252266
2. Basit H, Brito D, Sharma S. Hypertrophic Cardiomyopathy. [Updated 2023 Apr 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430788/