Biomarkers of Chronic Cardiac Injury and Hemodynamic Stress Identify a Malignant Phenotype of Left Ventricular Hypertrophy in the General Population

Objectives To determine if biomarkers of subclinical myocardial injury and hemodynamic stress identify asymptomatic individuals with left ventricular hypertrophy (LVH) at higher risk for heart failure (HF) and death. Background The interaction between LVH, low but detectable cardiac troponin T (cTnT), and elevated NT-proBNP on cardiovascular (CV) outcomes in the general population is unknown. Methods Participants in the Dallas Heart Study without clinical HF, LV dysfunction, or chronic kidney disease underwent measurement of LV mass by MRI, cTnT by highly sensitive assay, and NT-proBNP (n=2413). Subjects were stratified by LVH and by detectable cTnT (≥3 pg/mL) and increased NT-proBNP (>75th age- and sex-specific percentile). Results 9% of participants were LVH+, 25% cTnT+, and 24% NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n=144) were older, more likely to be male, with greater risk factor burden and more severe LVH compared with those LVH+ biomarker- (p<0.01 for each). The cumulative incidence of HF or CV death over 8 years among LVH+ cTnT+ was 21% vs. 1% (LVH- cTnT-), 4% (LVH- cTnT+), and 6% (LVH+ cTnT-), p<0.0001. The interactions between LVH and cTnT (pinteraction=0.0005) and LVH and NT-proBNP (pinteraction=0.014) were highly significant. Individuals LVH+ and either cTnT+ or NT-proBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those LVH- biomarker-. Conclusions Minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant sub-phenotype of LVH with high risk for progression to HF and CV death.