High-risk HCM patients had 3.44 times higher odds of elevated cTNI, 626.6 pg/ml higher NTproBNP, and 4-fold greater LGE extent than low-risk patients, indicating worse heart failure.
Do HCM patients at high risk for sudden cardiac death exhibit more advanced features of progressive heart failure compared to low-risk patients?
HCM patients at high risk for sudden cardiac death also exhibit a more malignant profile of progressive heart failure, highlighting the need to manage underlying heart failure once SCD risk is addressed.
Abstract Background The stratification of hypertrophic cardiomyopathy (HCM) patients according to their propensity for sudden cardiac death (SCD) is a crucial part of their clinical management. (1) However, the prevention of SCD represents only one aspect of the complex HCM disease trajectory, with the majority of mortality in HCM patients being attributed to progressive heart failure. (2) Objectives The aim of our study was to identify potential distinguishing features between high- and low-risk HCM patients, thereby establishing potential treatment targets. Methods We conducted a cross-sectional study of high- and low-risk patients, as defined by an ESC HCM risk score of ≥6% and 4%, respectively, who were referred to our clinic between 2020-2024. Demographic, clinical, laboratory and imaging data were retrieved and compared across the two groups. Intermediate risk patients (5-year SCD risk 4-6%) were excluded from the analysis. Results A total of 206 HCM patients were included in the analysis, with 50 patients allocated to the high-risk and 156 to the low-risk group. The mean HCM risk score was 7.94% and 1.95%, respectively. Genetic analysis was performed in 48% of high-risk versus 31% of low-risk patients. No differences were recorded in the genetic substrate between the two groups, with the majority of the patients showing either MYBPC3 or MYH7 pathogenic or likely pathogenic variants. High- risk patients presented more often with worsening heart failure symptoms, as evidenced by the more advanced stage of NYHA classification and the lower predicted maximal oxygen uptake in cardiopulmonary exercise test. Individuals in the high-risk group were also more likely to present with elevated levels of cardiac troponin I (cTNI) (OR 3.44, 95% CI: 1.73-6.96) and demonstrated higher NTproBNP levels (mean difference: 626.6, 95% CI: 249.2-1004.0) compared to low-risk patients. Furthermore, LGE was significantly higher in the high-risk group as compared to the low-risk (median 16% versus 4%, p0.001). A significant association was identified between LGE extent and elevated cTNI (beta=6.07, p0.001) (Figure 1). Notably, the extent of LGE also correlated with NTproBNP levels, exhibiting an increase of 1.7% per 1000 pg/ml of NTproBNP. The main results of our analysis are presented in Table 1. Conclusions In our cohort, patients characterized as high-risk for SCD using the HCM risk calculator were more likely to present with indications of worsening heart failure, including more compromised clinical status, lower exercise capacity, elevated levels of cTNI, higher levels of NTproBNP and more extended LGE, compared to low-risk individuals. These findings may signify a broader spectrum of the malignant profile of high-risk patients, indicative of the progressive heart failure, and alert us, once we have protected them from SCD, to direct our therapeutic attention toward managing the underlying heart failure process.LGE extent and cTNI levels relationship
Papageorgiou et al. (2025) studied this question. High-risk HCM patients had 3.44 times higher odds of elevated cTNI, 626.6 pg/ml higher NTproBNP, and 4-fold greater LGE extent than low-risk patients, indicating worse heart failure.