Left atrial remodelling in hypertrophic cardiomyopathy: relation with exercise capacity and biochemical markers of tissue strain and remodelling.

Background: Left atrial remodelling, assessed as left atrial volume (LAV), has been proposed as a good marker of left ventricular diastolic dysfunction. The aim of this study was to analyse the influence of LAV on exercise performance in hypertrophic cardiomyopathy (HCM), and in a subset of subjects, assess the relation of LAV and exercise performance to four biomarkers of disease pathophysiology: matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (as indices of tissue remodelling), N-terminal portion of pro B-type natriuretic peptide (NT-pro-BNP) (associated with ventricular dysfunction) and C-reactive protein (CRP, an index of inflammation).
Methods: We studied 75 consecutive HCM patients (aged 46 +/- 14 years, 56 men) where LAV was calculated assuming the ellipsoid model with two orthogonal planes. LAV was indexed to body surface area. Exercise capacity was evaluated by treadmill exercise test (symptom limited) and assessed with metabolic equivalent units (MET). Basal NT-pro-BNP and CRP levels were measured in 70 patients, whereas MMP-2 and TIMP-1 in 43 patients.
Results: Enlarged LAV was observed in those patients with previous atrial fibrillation (p = 0.016). Mean LAV was greater in patients with impaired functional New York Heart Association (NYHA) class (p < 0.001). LAV correlated with age (Spearman, r: 0.28), higher maximal left ventricular wall thickness (r: 0.32) and raised E/A ratio (r: 0.37) (all p < 0.01). LAV was significantly correlated with NT-pro-BNP values (r: 0.34; p = 0.04), MMP-2 (r: 0.32; p = 0.034), CRP (r: 0.33; p = 0.005) and correlated inversely with MET units (r: -0.39; p < 0.01). In multivariate analysis, MET units were only associated with NT-pro-BNP (p = 0.002) and LAV (p = 0.010).
Conclusions: Enlarged LAV is associated with impaired functional NYHA class and inversely with treadmill exercise capacity. Enlarged LAV is also associated with NT-pro-BNP, MMP-2 and CRP, perhaps as markers of disease severity and tissue remodelling. Age, LAV and NT-pro-BNP are independent predictors of exercise performance.