JACC. Heart failure · 2021
Spironolactone in Patients With an Echocardiographic HFpEF Phenotype Suggestive of Cardiac Amyloidosis: Results From TOPCAT.
СтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sperry Brett W, Hanna Mazen, Shah Sanjiv J, Jaber Wael A, Spertus John A
Аннотация
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.
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.