Wild-type transthyretin amyloid cardiomyopathy: spironolactone as a therapeutic option?

Abstract Introduction Wild-type transthyretin cardiac amyloidosis (wtATTR-CM) is increasingly recognized as an important cause of heart failure (HF). Although emerging evidence suggests that spironolactone may provide potential benefits in patients with wtATTR-CM and preserved ejection fraction, prospective clinical trials evaluating neurohormonal blockade in this population are still lacking. Objectives To evaluate the impact of spironolactone on clinical outcomes in patients with wtATTR-CM followed at a Cardiomyopathy Clinic in a regional hospital in Portugal. Methods Retrospective single-center study of patients diagnosed with wtATTR-CM according to the ESC algorithm between 2018 and 2024. Data on spironolactone use, as well as clinical, laboratory, echocardiographic, and electrocardiographic parameters were collected at the time of diagnosis (Table 1). The primary endpoint, a composite of hospitalization for HF or all-cause mortality, was assessed 18 months after diagnosis. Patients who achieved the primary endpoint (Group 1) were compared with those who did not (Group 2). Results A total of 70 patients were included; 94% were male, with a median age of 81 years (IQR 7). Baseline left ventricular ejection fraction (LVEF) was 55% (IQR 12). In this cohort, 36 patients (51%) were treated with spironolactone, and 34 patients (49%) achieved the primary endpoint. Baseline characteristics, including gender, hypertension, dyslipidemia, diabetes, conduction disturbances, echocardiographic parameters, and spironolactone use, were similar between groups. No differences were observed for other guideline-directed therapies, including beta-blockers, renin–angiotensin system inhibitors (RASI), and sodium-glucose co-transporter 2 inhibitors. Patients who achieved the primary endpoint more frequently had atrial fibrillation (82 vs 47%, p=0.002) and chronic kidney disease (79 vs 28%, p<0.001), higher NT-proBNP levels (4705.0 [IQR 5225.0] vs 2060.0 pg/mL [IQR 3250.0], p<0.001), and lower estimated glomerular filtration rate (eGFR) (46 [IQR 24] vs 67 [IQR 31], p=0.002). Survival analysis showed no significant differences in the primary endpoint between patients treated with or without spironolactone. Similarly, spironolactone use was not associated with the isolated endpoints of all-cause mortality or HF hospitalization. Conclusions In this cohort, spironolactone therapy was not associated with improved clinical outcomes, in contrast to recent studies, underscoring the need for further research to clarify the role of mineralocorticoid receptor antagonists in patients with wtATTR-CM.Table/Figure 1For image description, please refer to the figure legend and surrounding text.