Hussain Imad, Mohammed Selma F, Forfia Paul R, Lewis Gregory D, Borlaug Barry A, Gallup Dianne S, Redfield Margaret M
From the Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN (I.H., S.F.M., B.A.B., M.M.R.); Temple University, Philadelphia, PA (P.R.F.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston (G.D.L.); Duke Clinical Research Institute, Durham, NC (D.S.G.).
Circ Heart Fail. 2016 Apr;9(4):e002729. doi: 10.1161/CIRCHEARTFAILURE.115.002729.
Right ventricular (RV) dysfunction (RVD) is a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). The physiological perturbations associated with RVD or RV function indexed to load (RV-pulmonary arterial [PA] coupling) in HFpEF have not been defined. HFpEF patients with marked impairment in RV-PA coupling may be uniquely sensitive to sildenafil.
In a subset of HFpEF patients enrolled in the Phosphodiesteas-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial, physiological variables and therapeutic effect of sildenafil were examined relative to the severity of RVD (tricuspid annular plane systolic excursion [TAPSE]) and according to impairment in RV-PA coupling (TAPSE/pulmonary artery systolic pressure) ratio. The prevalence of atrial fibrillation and diuretic use, n-terminal probrain natriuretic peptide levels, renal dysfunction, neurohumoral activation, myocardial necrosis and fibrosis biomarkers, and the severity of diastolic dysfunction all increased with severity of RVD. Peak oxygen consumption decreased and ventilatory inefficiency (VE/VCO2 slope) increased with increasing severity of RVD. Many but not all physiological derangements were more closely associated with the TAPSE/pulmonary artery systolic pressure ratio. Compared with placebo, at 24 weeks, TAPSE decreased, and peak oxygen consumption and VE/CO2 slope were unchanged with sildenafil. There was no interaction between RV-PA coupling and treatment effect, and sildenafil did not improve TAPSE, peak oxygen consumption, or VE/VCO2 in patients with pulmonary hypertension and RVD.
HFpEF patients with RVD and impaired RV-PA coupling have more advanced heart failure. In RELAX patients with RVD and impaired RV-PA coupling, sildenafil did not improve RV function, exercise capacity, or ventilatory efficiency.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00763867.
右心室（RV）功能障碍（RVD）是射血分数保留的心力衰竭（HFpEF）患者预后不良的因素。HFpEF中与RVD或与负荷相关的右心室功能（右心室 - 肺动脉[PA]耦合）相关的生理紊乱尚未明确。右心室 - 肺动脉耦合明显受损的HFpEF患者可能对西地那非特别敏感。
在舒张性心力衰竭磷酸二酯酶 - 5抑制改善临床状态和运动能力（RELAX）试验纳入的一部分HFpEF患者中，研究了西地那非的生理变量和治疗效果与RVD严重程度（三尖瓣环平面收缩期位移[TAPSE]）的关系，并根据右心室 - 肺动脉耦合受损情况（TAPSE/肺动脉收缩压比值）进行分析。心房颤动的患病率、利尿剂使用情况、N末端脑钠肽前体水平、肾功能不全、神经体液激活、心肌坏死和纤维化生物标志物以及舒张功能障碍的严重程度均随RVD严重程度增加而升高。随着RVD严重程度增加，峰值耗氧量降低，通气效率低下（VE/VCO2斜率）增加。许多但并非所有生理紊乱与TAPSE/肺动脉收缩压比值的相关性更强。与安慰剂相比，在24周时，西地那非使TAPSE降低，而峰值耗氧量和VE/CO2斜率未改变。右心室 - 肺动脉耦合与治疗效果之间无相互作用，西地那非对患有肺动脉高压和RVD的患者的TAPSE、峰值耗氧量或VE/VCO2无改善作用。
患有RVD且右心室 - 肺动脉耦合受损的HFpEF患者心力衰竭更为严重。在RELAX试验中患有RVD且右心室 - 肺动脉耦合受损的患者中，西地那非未改善右心室功能、运动能力或通气效率。
