Diuretic Dose and NYHA Functional Class Are Independent Predictors of Mortality in Patients With Transthyretin Cardiac Amyloidosis

Abstract

Background: With increasing diagnoses and available treatment options for transthyretin amyloidosis cardiomyopathy (ATTR-CM), risk stratification of ATTR-CM patients is imperative. Objectives: We hypothesized that diuretic dose and New York Heart Association (NYHA) functional class are independent predictors of mortality in ATTR-CM and would be incrementally additive to existent risk scores. Methods: Consecutive ATTR-CM patients referred to a single center were identified. Adjusted Cox proportional hazards models determined the association between diuretic dose (furosemide equivalent in mg/kg) at time of diagnosis and the primary outcome of all-cause mortality. The incremental value of adding diuretic dose and NYHA functional class to existing ATTR-CM risk scores was assessed for discrimination and calibration. Results: 309 patients were identified, with mean age 73.2 ± 9.8 years, 84.1% male, and 66% wild type. Daily mean diuretic dose was 0.6 ± 1.0 mg/kg and significantly associated with all-cause mortality (unadjusted hazard ratio: 2.12 per 1-mg/kg increase, [95% confidence interval: 1.71 to 2.61] and fully adjusted hazard ratio: 1.43 [95% confidence interval: 1.06 to 1.93]). Testing previously published ATTR risk scores, adding diuretic dose as categories (0 mg/kg, >0 to 0.5 mg/kg, >0.5 to 1 mg/kg, and >1 to 2 mg/kg) improved the area under the curve of the Mayo risk score from 0.693 to 0.767 and the UK risk score from 0.711 to 0.787 while preserving calibration. Adding NYHA functional class further improved the area under the curve to 0.798 and 0.816, respectively. Conclusions: Diuretic dose and NYHA functional class are independent predictors of mortality in ATTR-CM patients and provide incremental value to existing ATTR-CM risk scores.

Keywords

• cardiac amyloidosis
• heart failure
• transthyretin