Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Circ Heart Fail. 2012 Sep 1;5(5):653-9. doi: 10.1161/CIRCHEARTFAILURE.112.969071.
Heart failure (HF) with preserved ejection fraction (HFpEF) or “diastolic HF” accounts for approximately half of HF cases. To date, neurohumoral antagonists have failed to show a significant benefit on clinical outcomes in HFpEF. While our understanding of the pathophysiology of HFpEF continues to develop, multiple therapeutic targets have been identified in HFpEF which may be modifiable by augmentation of the intracellular second messenger cyclic guanosine monophosphate (cGMP) via phosphodiesterase-5 inhibition (PDE5I) in HFpEF. The Phosphodiesteas-5 Inhibition to Improve Cinical Status nd Eercise Capacity in Diastolic Heart Failure (RELAX trial; clinicaltrials.gov NCT00763867) is being conducted within the NHLBI sponsored HF clinical research network and tests the hypothesis that chronic PDE5I (sildenafil® 20 mg tid for 12 weeks followed by 60 mg tid for 12 weeks) improves exercise capacity and clinical status in patients with HFpEF. Here we provide the rationale for RELAX by summarizing the pathophysiologic derangements in HFpEF and the evidence that PDE5I may ameliorate these derangements. The design of the RELAX trial is described and the rationale for the primary endpoint in RELAX (change in peak oxygen consumption) is provided.
射血分数保留的心力衰竭（HFpEF）或“舒张性心力衰竭”占心力衰竭病例的一半左右。迄今为止，神经激素拮抗剂并未显示出在 HFpEF 患者的临床结局上有显著获益。虽然我们对 HFpEF 的病理生理学的理解仍在不断发展，但在 HFpEF 中已经确定了多个治疗靶点，这些靶点可能可以通过抑制磷酸二酯酶 5（PDE5）来增加细胞内第二信使环鸟苷酸（cGMP）来改变，从而改善 HFpEF。磷酸二酯酶-5 抑制改善舒张性心力衰竭的临床状况和运动能力（RELAX 试验；clinicaltrials.gov NCT00763867）正在 NHLBI 赞助的心力衰竭临床研究网络中进行，该试验检验了慢性 PDE5（西地那非®20mg tid 持续 12 周，随后 60mg tid 持续 12 周）是否改善 HFpEF 患者的运动能力和临床状况的假设。在这里，我们通过总结 HFpEF 中的病理生理紊乱以及 PDE5 可能改善这些紊乱的证据，为 RELAX 提供了原理。描述了 RELAX 试验的设计，并提供了 RELAX 的主要终点（峰值耗氧量的变化）的原理。
