Potter Elizabeth, Stephenson Georgia, Harris Joanne, Wright Leah, Marwick Thomas H
Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
Eur J Heart Fail. 2022 Apr;24(4):620-630. doi: 10.1002/ejhf.2428. Epub 2022 Jan 27.
Subclinical left ventricular dysfunction (LVD) is a prelude to symptomatic heart failure (HF). We hypothesised that screening-guided treatment with spironolactone would prevent incident HF in at-risk patients.
We randomised asymptomatic, community-dwelling subjects aged ≥65 years old, with at least one non-ischaemic HF risk factor (hypertension, type 2 diabetes mellitus or obesity) to echocardiography-guided therapy or usual care. Spironolactone therapy was triggered by the detection of subclinical LVD (global longitudinal strain [GLS] ≤16%) or diastolic abnormalities (at least one of E/e' >15, E/e' >10 with left atrial enlargement [LAE] or impaired relaxation [E/A < 0.8, IR], LAE with IR), or borderline GLS (17%) with IR or borderline GLS with LAE. The primary outcome was incident HF at 24 months. Secondary outcomes were change in 6-min walk test (6MWT) and change in left ventricular function. LVD was identified in 161 (46%) of 349 participants (age 70 [68-73] years, 201 [58%] women). The trial was stopped because of a 55% rate of spironolactone discontinuation, due primarily to decline in renal function. Incident HF developed in 11 (3.5%) of 310 participants completing follow-up, with no difference between usual care and intervention (4 [2.5%] vs. 7 [4.7%], p = 0.29), decline in 6MWT distance (p = 0.28), persistent or new LVD (p = 0.58), nor change in GLS with intervention (p = 0.15). A per-protocol analysis of 131 patients with baseline LVD and a follow-up echocardiogram, showed resolution of LVD with spironolactone therapy (59% vs. 33%, p = 0.01).
The study was underpowered to determine whether screening-guided spironolactone therapy reduced incident HF because spironolactone was frequently discontinued due to renal function criteria. However, LVD resolved in more patients treated with spironolactone than in untreated patients. Future trials should use less conservative renal criteria for spironolactone discontinuation.
亚临床左心室功能障碍（LVD）是有症状心力衰竭（HF）的前奏。我们假设螺内酯筛查指导治疗可预防高危患者发生HF。
我们将年龄≥65岁、至少有一项非缺血性HF危险因素（高血压、2型糖尿病或肥胖）的无症状社区居民随机分为超声心动图指导治疗组或常规治疗组。螺内酯治疗由亚临床LVD（整体纵向应变[GLS]≤16%）或舒张功能异常（E/e'＞15、E/e'＞10伴左心房扩大[LAE]或舒张功能受损[E/A＜0.8，IR]、LAE伴IR中的至少一项），或临界GLS（17%）伴IR或临界GLS伴LAE触发。主要结局是24个月时发生HF。次要结局是6分钟步行试验（6MWT）的变化和左心室功能的变化。349名参与者中有161名（46%）被识别出有LVD（年龄70[68 - 73]岁，201名[58%]为女性）。该试验因螺内酯停药率达55%而提前终止，主要原因是肾功能下降。310名完成随访的参与者中有11名（3.5%）发生HF，常规治疗组和干预组之间无差异（4名[2.5%]对7名[4.7%]，p = 0.29），6MWT距离下降（p = 0.28），持续性或新发LVD（p = 0.58），干预组GLS也无变化（p = 0.15）。对131例有基线LVD且进行了随访超声心动图检查的患者进行符合方案分析，结果显示螺内酯治疗可使LVD得到缓解（59%对33%，p = 0.01）。
该研究因螺内酯常因肾功能标准而停药，故不足以确定筛查指导的螺内酯治疗是否能降低HF的发生率。然而，接受螺内酯治疗的患者中LVD缓解的人数多于未治疗患者。未来试验应采用不那么保守的肾功能标准来停用螺内酯。
