Long-term prognostic value of left ventricular outflow tract gradient in hypertrophic cardiomyopathy

Background

Hypertrophic cardiomyopathy (HCM) is classified as non-obstructive or obstructive, based on the presence of left ventricular outflow tract (LVOT) obstruction. The threshold for obstructive HCM is ≥ 30 mmHg whereas a gradient ≥ 50 mmHg is generally regarded as the threshold for clinically significant obstruction and potential therapeutic intervention. This distinction is crucial for patient management and risk stratification. Although LVOT gradients are routinely measured in HCM, its prognostic significance is not yet fully established, which is especially relevant now that LVOT obstruction has become a pharmacological target with cardiac myosin inhibitors.

Purpose

To investigate the prognostic value of LVOT gradient, measured at both rest and provoked during echocardiography, in HCM patients on a composite mortality endpoint consisting of all-cause mortality and the development of end-stage heart failure.

Methods

The study is a single-center, registry-based observational study conducted at a tertiary expertise HCM center in the Netherlands. Patients were included between 2004 and 2025 if they had an echocardiogram at baseline with LVOT gradient measurements and were not lost to follow-up in the Dutch Personal Records Database. The primary outcome was a composite endpoint of all-cause mortality and end-stage heart failure defined as heart transplantation and LVAD implantation.

Patients were stratified based on whether the LVOT gradient met the therapeutic threshold for significant obstruction (≥ 50 mmHg). Kaplan-Meier survival analyses and Cox proportional hazards models were used. We adjusted for relevant covariates: sex, age, New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF), left atrial dimensions and maximal septal wall thickness (MWT).

Results

A total of 983 HCM patients were included (median age 58 [IQR 47–67] years; 40% women; 42% NYHA I; 43% genotype positive; median maximal LVOT gradient 49 [IQR 9–92] mmHg) (Table 1). Over a median-follow up of 8.4 years, 170 events, 160 deaths and 10 end-stage heart failure, occurred (95 obstructive vs 85 non-obstructive). The Kaplan-Meier curves showed a lower event-free survival in oHCM (figure 1a) (log-rank p<0.001). After adjustment with multivariable Cox proportional hazards analysis age (p <0.001), LVEF (p=0.002) and MWT (p=0.04) were independently associated with adverse outcome, while LVOT gradient, sex, NYHA classification and left atrial dimensions were no longer significantly associated. Post-hoc stratified Kaplan-Meier survival curves (figure 1b) showed no survival difference in patients <57.5 years, whereas patients ≥57.5 years had more events overall, with lower event-free survival in obstructive HCM (p<0.001).

Conclusion

Obstructive HCM patients have more adverse outcomes, especially in the older population. Age, LV dysfunction and MWT are the main drivers of increased risk of composite mortality events in HCM.