Myocardial damage biomarkers in hypertrophic cardiomyopathy: prognostic role of high sensitivity cardiac troponin I and T.

Purpose: Hypertrophic cardiomyopathy (HCM) is a primary myocardium disease characterized by heterogeneous clinical presentation and natural history, ranging from asymptomatic forms to malignant expressions that may result in premature death or in progressive heart failure through several pathways. Myocardial ischemia is responsible for myocyte death and replacement fibrosis that play a crucial role in disease progression. Aim of this study was to assess cardiac troponin I and T values (hs-cTnI and hs-cTnT, measured using high sensitivity methods) in HCM, and to define their role in management of HCM patients and in outcome prediction. Methods: hs-cTnI and hs-cTnT concentrations were measured in 67 consecutive HCM patients by immunoassay, and the relation between biomarkers and clinical-instrumental parameters was evaluated. Age, gender, symptoms, ECG abnormalities, arrhythmias at Holter monitoring, echocardiographic and cardiac magnetic resonance data were collected. Patient with evidence of epicardial coronary artery disease were excluded. Serum hs-cTnI and hs-cTnT values were considered positive above the 99th percentile of a healthy volunteers population with a coefficient of variation<10%. The cut-off level was 0.045 μg/L and 14 ng/L for hs-cTnI and hs-cTnT, respectively. Results: Patients with positive troponins values (14 pts, 21% and 24 pts, 36% respectively for hs-cTnI and hs-cTnT) showed lower ejection fraction (EF) (54±10% vs 60±8%, p= 0.035 for hs-cTnI; 55±11% vs 61±7%, p= 0.05 for hs-cTnT), most severe diastolic dysfunction (prevalence of restrictive pattern 21% vs 5%, p= 0.02 for hs-cTnI; and 22% vs 0%, p= 0.002 for hs-cTnT), and ischemic ECG abnormalities, i.e. ST-segment downsloping (57% vs 11%, p= 0.0002 for hs-cTnI; 42% vs 9%, p= 0.002, for hs-cTnT). At multivariate analysis, using models considering also age and gender, inverse-linear relationships were found among ln hs-cTnT, EF and diastolic dysfunction (R2 0.26, adjusted R2 0.23, p= 0.0002), as well as among ln hs-cTnI, ST-segment downsloping and the presence of ventricular tachiarrhythmias (R2 0.33, adjusted R2 0.30, p< 0.0001). During a mean follow-up of 26±18 months, patients with at least one hs-cTn value above the 99th percentile had worse outcome by Kaplan-Meier curves considering combined endpoint (progressive severe heart failure, heart-failure related death or cardiac transplantation) (p= 0.04). Conclusions: High-sensitivity cardiac troponins are interesting markers of HCM progression to advanced heart failure in setting of impaired systolic function and/or severe diastolic dysfunction and useful predictors of prognosis.