Cardiovascular determinants of the 6-minute walk distance in cardiac transthyretin amyloidosis.

backgroundThe six-minute walk distance (6MWD) is a measure of functional capacity and a frequently used endpoint in clinical trials investigating transthyretin amyloid cardiomyopathy (ATTR-CM). We evaluated the clinical utility of the 6MWD by quantifying the gap between the expected and observed physical performance and estimating its determinants.

methodsOutpatients with wild-type (ATTRwt)-CM were investigated. Standardized echocardiographic, laboratory and clinical assessments were performed. A regression formula derived from a healthy local population sample was applied to predict the expected 6MWD. Associations with 6MWD were analyzed by linear regression, adjusted for age and height. Explanatory multivariable models using backward elimination, regularization and clinical reasoning were calculated.

results100 patients were analyzed. Their mean age was 78.7 (6.3) years and 86% were men. The mean observed 6MWD was 310 (113) m, which corresponded to about 65% of the expected performance. Significant predictors of the 6MWD were (ordered by decreasing explanatory power): high-sensitivity Troponin T, NT-proBNP, NAC disease stage, estimated glomerular filtration rate, atrial fibrillation, hemoglobin, hepatic vein dilation, mitral E-wave maximum velocity, left ventricular ejection fraction, and the tricuspid valve maximal regurgitation pressure gradient. Multivariable models yielded an R² of up to 45.9% with a root mean squared error of 82.9 m.

conclusionsPhysical performance as measured by the 6MWD in patients with ATTRwt-CM was remarkably compromised. Laboratory and imaging markers indicative of disease severity and congestion predicted the 6MWD in these patients. Cardiovascular markers explained a fair amount of 6MWD variability.