Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 795-802 |
| Number of pages | 8 |
| Journal | JACC: Heart Failure |
| Volume | 9 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2021 |
Funding
Dr Shah is supported by U.S. National Institutes of Health research grants R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423; has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and is a consultant for Abbott, Actelion, AstraZeneca, Amgen, Axon Therapies, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiora, CVRx, Cytokinetics, Eidos, Eisai, GlaxoSmithKline, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr Sperry is a consultant for Alnylam and Pfizer; and has received research funding from Pfizer. Dr Hanna has served on advisory boards for Alnylam, Eidos, AKCEA, and Pfizer. Dr Spertus is a consultant for Janssen, Bayer, Myokardia, Novartis, Merck Amgen, and United Healthcare and he is a member of the Board of Directors of Blue Cross Blue Shield of Kansas City; and owns the copyrights to the Seattle Angina Questionnaire, Kansas City Cardiomyopathy Questionnaire, and Peripheral Artery Questionnaire. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Keywords
- aldosterone
- angiotensin
- diastolic heart failure
- mineralocorticoid receptor antagonist
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine