Effect of Cardiac Resynchronization Therapy on Exercise-Induced Pulmonary Hypertension and Right Ventricular-Arterial Coupling: A Cardiopulmonary Exercise Testing Imaging Evaluation

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Background:Acute and chronic effects of cardiac resynchronization therapy (CRT) on pulmonary pressures, right ventricular function, and ventricular-vascular coupling during exercise are insufficiently understood. Yet, these factors are strongly associated with functional status and outcome.Methods and Results:Heart failure patients with reduced ejection fraction indicated for CRT were prospectively included to undergo exercise echocardiography simultaneously with cardiopulmonary exercise testing before (pre_CRT), 1 day after (post_CRT), and 6 months (post6_CRT) after CRT implant. Right ventricular-arterial coupling was assessed by the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (SPAP) ratio. A total of 31 heart failure patients with reduced ejection fraction (age=66±13 years) were prospectively included. CRT resulted in an immediate reduction in rest SPAP (pre_CRT=32±16 versus post_CRT=23±16 mm Hg; P=0.006) and rest effective regurgitant orifice (pre_CRT=0.32±0.1 versus post_CRT=0.18±0.2; P=0.001) without changes in exercise mitral regurgitation or exercise SPAP indexed for cardiac output. Six months after CRT, in parallel with left ventricular reverse remodeling and a reduction in exercise mitral regurgitation and exercise E/e′ ratio, the exercise SPAP/cardiac output significantly improved (post_CRT=5.6±3.1 versus post6_CRT=4.3±2.9 mm Hg·L−1·min−1; P=0.039), which was also illustrated by a reduced slope of ΔSPAP/Δcardiac output (post_CRT=5.2±3.7 versus post6_CRT=2.9±2.7 mm Hg·L−1·min−1; P=0.002). CRT did not result in an acute or chronic effect on TAPSE or TAPSE/SPAP ratio at rest. However, exercise revealed the presence of right ventricular-arterial uncoupling which was not affected by an acute CRT effect (P=0.396) but only improved by a chronic CRT effect (P<0.001; TAPSE/SPAP ratio: pre_CRT= 0.39±0.6 mm/mm Hg; post_CRT=0.42±0.5 mm/mm Hg; post6_CRT =0.84±0.12 mm/mm Hg). Of all exercise echocardiography variables, the TAPSE/SPAP ratio demonstrated the strongest correlation with VO2 peak (r=0.475), VE/VCO2 (r=−0.585), and workload (r=0.476) during cardiopulmonary exercise testing (P<0.05 all). Multivariate predictors affecting exercise ventricular-arterial coupling after CRT included metrics of residual exercise mitral regurgitation and systolic and diastolic left ventricular function.Conclusions:Chronic CRT beneficially influences pulmonary pressures and right ventricular-arterial coupling during exercise, which strongly relates to functional status. These findings are mechanistically linked to reverse remodeling with improved interventricular dependence and reduction in exercise mitral regurgitation.

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