Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis
Elliot J. Stein, William F. Fearon, Sammy Elmariah, Juyong B. Kim, Samir Kapadia, Dharam J. Kumbhani, Linda Gillam, Brian Whisenant, Nishath Quader, Alan Zajarias, Frederick G. Welt, Anthony A. Bavry, Megan Coylewright, Robert N. Piana, Ravinder R. Mallugari, Daniel E. Clark, Jay N. Patel, Holly Gonzales, Deepak K. Gupta, Anna Vatterott, Natalie Jackson, Shi Huang, Brian R. Lindman
Abstract
Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core‐laboratory‐measured LV mass index, cTnT, and NT‐proBNP. LVH was defined by sex‐specific guideline cut‐offs and elevated biomarker levels were based on age and sex cut‐offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all‐cause death out to 5 years. Elevated cTnT and NT‐proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively ( P <0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01–1.77, P =0.043). cTnT and NT‐proBNP each risk stratified patients with moderate/severe LVH ( P <0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45–3.00, P <0.001) and elevated NT‐proBNP (aHR, 1.46; 95% CI 1.00–2.11, P =0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not ( P =0.15). Conclusions Elevations in circulating cTnT and NT‐proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT‐proBNP predict post‐transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.