Coronary artery disease and comorbidity spectrum impact on prognosis in hypertrophic cardiomyopathy

Christoph Reich (Heidelberg)1, A. Amr (Heidelberg)1, F. Sedaghat-Hamedani (Heidelberg)1, J. Kölemen (Heidelberg)1, E. Kayvanpour (Heidelberg)1, N. Frey (Heidelberg)1, B. Meder (Heidelberg)1

1Universitätsklinikum Heidelberg Klinik für Innere Med. III, Kardiologie, Angiologie u. Pneumologie Heidelberg, Deutschland


Background: The concomitant prevalence, natural history, and clinical significance of coronary artery disease (CAD) in patients with hypertrophic cardiomyopathy (HCM) has not been sufficiently examined. Symptomatic HCM patients often present with chest pain and hence require exclusion of CAD. In this study, we analyzed patients with primary HCM who underwent coronary angiography and compared them to an age and sex-matched patient cohort. 

Methods: In an observational, longitudinal, single center cohort study, patients ≥ 18 years of age suffering from HCM were enrolled. Data from coronary angiography examinations of 222 HCM patients and 222 matched controls were analyzed. We performed cluster analysis from quantitative coronary angiography scores. Two clusters were identified based on the severity of coronary stenosis in the 15-segment model. The clustering differentiated HCM patients into groups with significant CAD and non-significant CAD. The patient characteristics of each cluster group were compared. Finally, we also compared the clustering of a 1:1 nearest neighbor matched non-HCM CAD control group to investigate whether different patterns of CAD occur in HCM.

Results: The mean age was 55.6 ± 14.0 years for HCM patient population and 60.0 ± 12.7 years for the control group. The majority of the HCM patients were not severely limited by heart failure symptoms (NYHA class I and II 80%). The obstructive form of the disease was less prevalent and was present in 44%. Patients categorized in the CAD cluster were more symptomatic, with a greater number of patients reporting NYHA classification 2 or higher. The presence of cardiovascular risk factors, such as arterial hypertension (p < 0.001), diabetes mellitus (p = 0.021), and advanced age (p = 0.001), differed significantly between the two HCM groups at the time of the coronary angiography, underscoring their importance in the context of CAD. Interestingly, we find that patients with a genetic predisposition for HCM exhibited a lower severity and prevalence of CAD (26.6% vs. 6.1%; p = 0.004). The mean follow-up duration was 9.7 years ± 5.1, during which 38 (17.1%) HCM patients died. Patients with significant CAD had a statistically significant lower survival rate compared to those without significant CAD (p < 0.001). However, this was attributed to an age effect using adjusted Cox regression and a trend for CAD cluster (p = 0.075). Comparison of CAD patterns between control groups and HCM patients revealed no distinct clustering associated with the HCM phenotype across the 15 coronary segments analyzed.

Discussion: Patients with HCM often develop CAD, especially in the presence of traditional risk factors including age. Co-existing significant CAD negatively affects survival in HCM patients, thus highlighting its relevance especially with the introduction of new treatments such as mavacamten. A comprehensive clinical workup to exclude CAD as the cause of symptoms in HCM patients, as well as detecting and treating the disease in early stages, is recommended.

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