Outpatient Diuretic Intensification: a Simple Prognostic Marker in Cardiac Transthyretin Amyloidosis

Background: Currently, simple clinical parameters indicating disease progression are lacking in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate the prognostic value of outpatient diuretic intensification (ODI) in ATTR-CM patients.

Methods: This retrospective study examined ATTR-CM patients at a tertiary care center between August 1, 2020, and June 30, 2023. ODI was defined as any loop diuretic increase within six months after baseline visit, and its impact on all-cause mortality and hospitalization for heart failure (HF) was analyzed.

Results: Altogether, 182 patients were included (median age 80 [76;84] years; 88% male), and 25% experienced ODI (median increase 10 [10;40] mg furosemide equivalent). Independent predictors of ODI were higher baseline New York Heart Association (NYHA) class and polyneuropathy. Both any ODI and the magnitude of furosemide equivalent increase were significantly associated with mortality and HF hospitalization during a median follow-up of 17 months. After adjusting for baseline NYHA class and National Amyloidosis Centre stage, significantly increased risk of all-cause mortality (hazard ratio [HR] 2.38, 95%-confidence interval [CI]: 1.03-5.53;p=0.043) and HF hospitalization (HR 3.27, 95%-CI: 1.41–7.60;p=0.006) persisted in patients with ODI. Its prognostic value was similar in strata of age, ATTR subtype, previous cardiac decompensation, biomarkers, left ventricular ejection fraction, 6-minute walk distance, and tafamidis treatment.

Conclusions: ODI occurred in 1 in 4 ATTR-CM patients within six months and was associated with more severe baseline amyloid organ manifestations. ODI and the magnitude of diuretic dose increase provide easily assessable clinical markers of disease progression in patient monitoring.