Blood-based biomarkers for the prediction of hypertrophic cardiomyopathy prognosis: a systematic review and meta-analysis

Aims: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease. HCM is an important cause of sudden cardiac death and may also lead to outflow tract obstruction and heart failure. Disease severity is highly variable and risk stratification remains limited. Therefore, we aimed to review current knowledge of prognostic blood-based biomarkers in HCM. Methods and results: A systematic literature search was performed on PubMed, Embase, and the Cochrane library to identify studies assessing plasma or serum biomarkers for outcomes involving malignant ventricular arrhythmia, outflow tract obstruction, and heart failure. Risk of bias was assessed using the QUIPS tool. Meta-analyses were performed using the random effects method. A total of 26 unique cohort studies assessing 42 biomarkers were identified. Overall risk of bias was moderate. Thirty-two biomarkers were significantly associated to an HCM outcome in at least one study (nine biomarkers in at least two studies). In pooled analyses, cardiovascular mortality was predicted by N-terminal prohormone of brain natriuretic peptide (hazard ratio [HR] 5.38 per log[pg/mL], 95% confidence interval [CI] 2.07–14.03, P < 0.001, I² = 0%) and high-sensitivity C-reactive protein (HR 1.30 per μg/mL, 95% CI 1.00–1.68, P = 0.05, I² = 78%), all-cause mortality by low-density lipoprotein cholesterol (HR 0.63 per μmol/mL, 95% CI 0.49–0.80, P < 0.001, I² = 0%), and a combined congestive heart failure, malignant ventricular arrhythmia, and stroke outcome by high-sensitivity cardiac troponin T (pooled HR 4.19 for ≥0.014 ng/mL, 95% CI 2.22–7.88, P < 0.001, I² = 0%). Quality of evidence was low–moderate. Conclusions: Several blood-based biomarkers were identified as predictors of HCM outcomes. Additional studies are required to validate their prognostic utility within current risk stratification models.