Risk prediction in ATTR-CM patients under tafamidis treatment: results from the multicentre SWISS-CARE registry

Background/Introduction Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an increasingly recognised heart failure (HF) aetiology. Whether established risk factors from early trials apply to contemporaneous patients under disease-modifying therapy remains unknown. Purpose To identify independent predictors of major adverse cardiac events (MACE) in tafamidis-treated ATTR-CM patients from a multicentre domestic registry. Methods A total of 452 prospectively included tafamidis-treated patients with scintigraphy- or biopsy-proven wild-type ATTR-CM from six Swiss tertiary centres participating in the SWISS-CARE registry were analysed. All received tafamidis 61 mg daily with 12-month follow-up intervals (median 698 days, Q1-Q3: 361–1182). Variables predicting first MACE (HF hospitalisation, sustained ventricular tachycardia, cardiovascular death) were analysed using multivariable Cox proportional hazard models. Results Patients were predominantly male (93%), median age 79 (74–82) years, with NYHA class II/III (71%/12%) and NAC stage I/II (67%/23%). During follow-up, 55 (12.2%) patients died and 90 had a first HF hospitalisation (19.9%). First MACE occurred in 113 (25%) patients at median 558 days (318–1025). Patients who experienced MACE were significantly older, had a higher NYHA class, increased NT-proBNP, reduced renal function and LVEF (all p<0.001). Adjusted multivariable analysis identified independent MACE predictors: age (years) (HR 1.31, 95% CI: 1.03–1.65, p<0.05), arterial hypertension (HR 1.61, 95% CI: 1.07–2.41, p<0.05), NT-proBNP (pg/mL) (HR 1.31, 95% CI: 1.03–1.68, p<0.05), and moderate-to-severe tricuspid valve disease (HR 1.61, 95% CI: 1.08–2.41, p<0.05). Higher LVEF was independently associated with lower risk (HR 0.81, 95% CI: 0.67–0.98, p<0.05). Conclusions In a contemporaneous cohort of tafamidis-treated ATTR-CM patients, age, hypertension, NT-proBNP, and moderate-to-severe tricuspid valve disease identify those at increased residual risk despite disease-modifying therapy, whilst higher LVEF indicates lower risk.