Outpatient worsening of heart failure and mortality in transthyretin amyloid cardiomyopathy.

Aims: Transthyretin cardiomyopathy (ATTR-CM) is characterized by episodes of worsening heart failure (WHF) which can include heart failure (HF) hospitalizations or urgent unplanned visits for administration of intravenous diuretics. WHF characterized by outpatient intensification of oral loop diuretics is common yet its prognostic implications for ATTR-CM patients relative to other WHF events remains unclear. We assessed how WHF characterized by outpatient diuretic intensification (ODI) relates to mortality in this population.

Methods And Results: This was a retrospective study of ATTR-CM patients presenting to the Columbia University Irving Medical Center. Oral loop diuretic dose was recorded longitudinally. WHF characterized by ODI was defined as a persistent increase in oral loop diuretic dose lasting >1 month. We analysed the all-cause mortality rate after either WHF event (hospitalization or ODI) relative to subjects who had no WHF event. Overall, 303 patients highly treated with tafamidis were included: 152 (50.2%) patients had no WHF events, 35 (11.6%) experienced HF hospitalization, and 145 (47.9%) experienced ODI; 29 (9.6%) patients experienced both WHF events. Patients experiencing ODI had higher rates of subsequent mortality (17.7 per 100 person-years; 95% confidence interval [CI] 13.3-23.7) as did those with a HF hospitalization (29.8 per 100 person-years; 95% CI 17.7-50.3) than patients without WHF events (5.0 per 100 person-years; 95% CI 3.0-8.3) on log-rank test. WHF characterized by ODI was independently associated with mortality in a model adjusting for age, genotype, atrial fibrillation, disease duration, time-varying tafamidis use and National Amyloid Centre (NAC) or Columbia stages.

Conclusion: In contemporary patients with ATTR-CM treated with tafamidis, WHF requiring ODI is prognostic of subsequent mortality and is a clinical marker of disease progression.