Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction.
Left Atrial Remodeling and Atrioventricular Coupling in a Canine Model of Early Heart Failure With Preserved Ejection Fraction.
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DOI：
10.1161/circheartfailure.115.003238
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发表时间：
2016-10
期刊：
影响因子：
--
通讯作者：
Redfield MM
中科院分区：
文献类型：
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作者：
Zakeri R;Moulay G;Chai Q;Ogut O;Hussain S;Takahama H;Lu T;Wang XL;Linke WA;Lee HC;Redfield MM
Left atrial (LA) compliance and contractility influence left ventricular (LV) stroke volume. We hypothesized that diminished LA compliance and contractile function occur early during development of heart failure with preserved ejection fraction (HFpEF) and impair overall cardiac performance. Cardiac magnetic resonance imaging, echocardiography, LV 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% CI 13–24] vs 12[10–14]%, p=0.008; end-systolic pressure-volume relationship slope 2.4[1.9–3.2]mmHg/mL HFpEF vs 1.5[1.2–2.2]mmHg/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, βLA, 0.16[0.11–0.18]mmHg/mL vs 0.06[0.04–0.10]mmHg/mL controls, p=0.002) indicating reduced LA compliance. Impaired atrioventricular coupling and lower LA compliance correlated with lower LV stroke volume. Total fibrosis and titin isoform composition were similar between groups, however titin was hyperphosphorylated in HFpEF and correlated with βLA. LA microvascular reactivity was diminished in HFpEF versus controls. LA microvascular density tended to be lower in HFpEF and inversely correlated with βLA. 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 LV stroke volume. These data indicate that maladaptive LA remodeling occurs early during HFpEF development, supporting a concept of global myocardial remodeling.
