One-year outcomes of patients with hypertrophic cardiomyopathy according to levels of inflammatory biomarkers

Abstract

Abstract Background Hypertrophic cardiomyopathy (HCM) is a vastly heterogeneous sarcomere disorder unified by maximal left ventricular (LV) thickness increases. The lifetime relative risk of morbidity in HCM is four-fold higher than in the general population, primarily driven by arrhythmias and heart failure (HF). Numerous prognostic features have been identified, but our ability to identify high-risk patients of progression remains rudimentary. Small retrospective studies have shown that systemic inflammation is associated with adverse outcomes in patients with HF; others, small and single-center, have also shown associations between adverse outcomes and inflammation in HCM. Purpose We aimed to determine whether elevated levels of inflammatory biomarkers are associated with an increased risk of acute heart failure (AHF) and mortality at 1 year in a large cohort of patients with HCM across multiple centers in the United States (US). Methods In this retrospective study, using the US cohort of 60 healthcare organizations in the TriNetX database, we included more than 85,000 adult patients with HCM (ICD-10-CM codes I42.1 and I42.2) between 2004 and 2024. Patients were divided according to predetermined cut-offs of different inflammatory biomarkers (C-reactive protein [CRP], <2 mg/L vs. 2-100 mg/L; white blood cells [WBC], < vs. ≥ the median [8x10^3/µL]; neutrophils [Neu], < vs. ≥ the median [5x10^3/µL]). These cohorts were then 1:1 propensity score matched (PSM) for age, sex, and race. We used Kaplan-Meier survival curves to derive cumulative incidence curves (as 1 minus Kaplan-Meier survival estimates) for AHF (ICD-10-CM codes I50.21, I50.23, I50.31, I50.33, I50.41, I50.43) or death, and we compared them with the Log-rank (Mantel-Cox) test. We also derived Hazard Ratios (HR) with 95% Confidence Interval (CI) from Cox regression analysis to compare the outcomes within the groups at 1-year. Results After PSM, patients with HCM and CRP levels between 2-100 mg/L experienced higher rates of the composite outcome (19.6% vs. 12.2%, Log-rank p<0.001; HR 1.67, 95% CI [1.29-2.16]), as well as the separate outcomes of death (14.7% vs. 6.8%, Log-rank p<0.001; HR 2.23, 95% CI [1.68-2.98]) and AHF (10.9% vs. 7.5%, Log-rank p<0.001; HR 1.49, 95% CI [1.07-2.07]), compared to those with CRP <2 mg/L (Table 1)(Figure 1). Similarly, patients with Neu ≥5x10^3/µL reported higher incidences of the composite outcome (20.3% vs. 13.2%, Log-rank p<0.001; HR 1.62, 95% CI [1.55-1.68]) and the separates outcomes, compared to those with Neu <5x10^3/µL (Table 1) (Figure 1). Patients with WBC ≥8x10^3/µL also had increased rates of the composite outcome (19.4% vs. 14.1%, Log-rank p<0.001; HR 1.43, 95% CI [1.38-1.48]) and the separate outcomes, compared to those with WBC <8x10^3/µL (Table 1)(Figure 1). Conclusions In the first large 'real world' analysis of patients with HCM, elevated levels of inflammatory biomarkers were associated with worse outcomes of death and acute heart failure.