Multidimensional Assessment of Disease Progression in a Contemporary Population With Transthyretin Amyloid Cardiomyopathy: Integrating Clinical Parameters, Biomarkers, Functionality, and Patient-Reported Outcomes.

BACKGROUND

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease. With the availability of multiple disease-modifying therapies, improved monitoring strategies are needed to optimize management. Integrating clinical parameters, biomarkers, functional assessments, and health-related quality of life (HR-QOL) via patient-reported outcomes provides a more accurate characterization of disease progression in ATTR-CM.

METHODS

This is a prospective observational study of patients with ATTR-CM who were followed at Columbia University Irving Medical Center. Disease progression was defined across 4 domains: (1) clinical parameters (New York Heart Association [NYHA] class of worsening or outpatient worsening heart failure characterized by increased oral loop diuretics; (2) biomarkers (NT-proBNP increase >700 pg/mL and >30%, or estimated glomerular filtration rate decline >20%); (3) functionality (6-minute-walk-test [6MWT] decline >35m or >5%, or Short Physical Performance Battery (SPPB) decline ≥1 point); and (4) HR-QOL (Kansas City Cardiomyopathy Questionnaire-overall score [KCCQ-OS] decrease >5 points or SF-36v2 (a short-form health survey) decline >0.5 × standard deviation (SD). The combined endpoints included all-cause mortality and cardiovascular hospitalization.

RESULTS

Of the 158 patients (91% male, median age 78.5 years) who were included, most of them were in early stages (68% National Amyloidosis Centre, stage 1), and all of them were taking disease-modifying therapy. At follow-up, 23% had clinical worsening (7% NYHA, 11% outpatient worsening heart failure, and 5% both). Biomarker worsening occurred in 21.5% (9% NT-proBNP rise, 9% estimated glomerular filtration rate decline, 4.5% both). Functional decline was observed in 54.9% (22.9% 6-Minute Walk Test, 21% Short Physical Performance Battery Test, 11.1% both). HR-QOL worsening was reported in 44% (15% KCCQ, 16% -36v2, 13% both). In total, 69% of patients showed disease progression in at least 1 domain. A progression score (0-4 points) was created by assigning 1 point per worsening domain, which was associated with increased risk of the combined endpoint (HR = 2.54 per point; 95% CI:1. 68-3.85; P < 0.001).

CONCLUSIONS

Disease progression is common in patients with ATTR-CM who are taking disease-modifying therapy, and integrating a multimodal assessment provides a comprehensive framework for monitoring progression across more domains; it was associated with an increased risk of adverse events.