Spironolactone in Patients With an Echocardiographic HFpEF Phenotype Suggestive of Cardiac Amyloidosis,JACC: Heart Failure

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Spironolactone in Patients With an Echocardiographic HFpEF Phenotype Suggestive of Cardiac Amyloidosis
JACC: Heart Failure ( IF 10.3 ) Pub Date : 2021-09-08 , DOI: 10.1016/j.jchf.2021.06.007
Brett W Sperry ₁ , Mazen Hanna ₂ , Sanjiv J Shah ₃ , Wael A Jaber ₂ , John A Spertus ₁

Affiliation

Objectives

This study investigated an enriched cohort of patients with heart failure and preserved ejection fraction (HFpEF) in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) with an echocardiographic phenotype of cardiac amyloidosis.

Background

There is a high prevalence of increased interventricular septal (IVS) thickness and decreased mitral annular systolic (s′) velocity in cardiac amyloidosis. In addition, clinical trials of neurohormonal blockade are missing in this population.

Methods

TOPCAT randomized patients with HFpEF to spironolactone or placebo therapy with a primary endpoint of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Patients with IVS and s′ velocity measurements were included, and adjusted Cox models assessed the effect of echocardiographic variables and spironolactone on the primary endpoint.

Results

Among 590 patients, mean s′ velocity was 6.4 ± 2.1 cm/s and IVS thickness was 1.2 ± 0.2 cm. The enriched cohort with characteristics of cardiac amyloidosis (s′ velocity ≤6 cm/s and IVS thickness ≥1.2 cm) included 135 patients (23% of the cohort). After a median follow-up of 2.6 years (1.5-3.9 years), these patients had the worst prognosis (adjusted HR: 2.10; 95% CI: 1.26-3.50; P = 0.004). Both s′ velocity and IVS thickness were individually associated with the primary endpoint, and abnormalities in these parameters were additive as lower s′ velocity was particularly prognostic in those with greater IVS thickness (interaction: P = 0.013). Spironolactone was associated with improved outcomes in the overall cohort (P = 0.024), and patients in the enriched cohort had a benefit similar to that in other groups (interaction: P = 0.382).

Conclusions

An enriched subset of patients with structural and functional echocardiographic features of cardiac amyloidosis had the worst prognosis in the TOPCAT study, but they benefitted similarly from spironolactone therapy. Future studies of mineralocorticoid receptor antagonists in patients with cardiac amyloidosis are warranted.

中文翻译：

超声心动图 HFpEF 表型提示心脏淀粉样变性患者的螺内酯

目标

本研究调查了 TOPCAT（用醛固酮拮抗剂治疗保留心脏功能心力衰竭）中具有心脏淀粉样变性的超声心动图表型的心力衰竭和保留射血分数 (HFpEF) 患者的丰富队列。

背景

在心脏淀粉样变性中，室间隔 (IVS) 厚度增加和二尖瓣环收缩 (s') 速度降低的患病率很高。此外，该人群缺少神经激素阻断的临床试验。

方法

TOPCAT 将 HFpEF 患者随机分配至螺内酯或安慰剂治疗，主要终点为心血管死亡、心衰住院或心脏骤停中止。包括 IVS 和 s' 速度测量的患者，调整后的 Cox 模型评估了超声心动图变量和螺内酯对主要终点的影响。

结果

在 590 名患者中，平均 s' 速度为 6.4 ± 2.1 cm/s，IVS 厚度为 1.2 ± 0.2 cm。具有心脏淀粉样变性特征（s' 速度 ≤6 cm/s 和 IVS 厚度 ≥1.2 cm）的丰富队列包括 135 名患者（队列的 23%）。在中位随访 2.6 年（1.5-3.9 年）后，这些患者的预后最差（调整后的 HR：2.10；95% CI：1.26-3.50；P = 0.004）。s' 速度和 IVS 厚度均与主要终点单独相关，并且这些参数的异常是相加的，因为较低的 s' 速度在 IVS 厚度较大的患者中尤其具有预后意义（交互作用：P = 0.013）。螺内酯与整个队列的结局改善相关（P =0.024），并且富集队列中的患者具有与其他组相似的益处（交互作用：P = 0.382）。