Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction
- 1 October 2016
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation: Heart Failure
Abstract
Background—: Left atrial (LA) compliance and contractility influence left ventricular stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during the development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. Methods and Results—: Cardiac magnetic resonance imaging, echocardiography, left ventricular and LA pressure-volume studies, and tissue analyses were performed in a model of early HFpEF (elderly dogs, renal wrap-induced hypertension, exogenous aldosterone; n=9) and young control dogs (sham surgery; n=13). Early HFpEF was associated with LA enlargement, cardiomyocyte hypertrophy, and enhanced LA contractile function (median active emptying fraction 16% [95% confidence interval, 13–24]% versus 12 [10–14]%, P =0.008; end-systolic pressure-volume relationship slope 2.4 [1.9–3.2]mm Hg/mL HFpEF versus 1.5 [1.2–2.2]mm Hg/mL controls, P =0.01). However, atrioventricular coupling was impaired and the curvilinear LA end-reservoir pressure-volume relationship was shifted upward/leftward in HFpEF (LA stiffness constant [β LA ] 0.16 [0.11–0.18]mm Hg/mL versus 0.06 [0.04–0.10]mm Hg/mL controls; P =0.002), indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower left ventricular stroke volume. Total fibrosis and titin isoform composition were similar between groups; however, titin was hyperphosphorylated in HFpEF and correlated with β LA . LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with β LA . Conclusions—: In early-stage hypertensive HFpEF, LA cardiomyocyte hypertrophy, titin hyperphosphorylation, and microvascular dysfunction occur in association with increased systolic and diastolic LA chamber stiffness, impaired atrioventricular coupling, and decreased left ventricular stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling.Keywords
This publication has 40 references indexed in Scilit:
- Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fractionCardiovascular Research, 2012
- Left Atrial Function Predicts Heart Failure Hospitalization in Subjects With Preserved Ejection Fraction and Coronary Heart DiseaseJournal of the American College of Cardiology, 2012
- Mineralocorticoid Accelerates Transition to Heart Failure With Preserved Ejection Fraction Via “Nongenomic Effects”Circulation, 2010
- PKC Phosphorylation of Titin’s PEVK ElementCirculation Research, 2009
- Left Atrial Volume and Geometry in Healthy AgingCirculation: Cardiovascular Imaging, 2009
- Mineralocorticoid Signaling in Transition to Heart Failure With Normal Ejection FractionHypertension, 2008
- Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failureCardiovascular Research, 2004
- Assessment of left atrial volumes and phasic function using cine magnetic resonance imaging in normal subjectsThe American Journal of Cardiology, 1994
- The clinical consequences of a stiff left atriumAmerican Heart Journal, 1991
- Left atrial afterload mismatch in hypertrophic cardiomyopathyThe American Journal of Cardiology, 1991