R. Willixhofer, Centro Cardiologico Monzino, IRCCS, Milan, Italy.
E. Salvioni, N. Capra, M. Contini, J. Campodonico and P. Agostoni

Physiol Rep 2025 Vol. 13 Issue 9 Pages e70308

In cardiac amyloidosis (CA) cardiopulmonary exercise testing (CPET) is underexplored. This study evaluated exercise limitations in CA using CPET, focusing on the ventilation-to-carbon dioxide production (VE/VCO(2)) slope and peak oxygen uptake (VO(2)). Seventeen studies involving 1505 patients were analyzed and systematically reviewed according to PRISMA reporting guidelines. Subgroup analyses assessed differences by diagnosis (ATTR vs. AL), CPET modality, and age. The cohort included 12% with AL, 80% with ATTR (23% hereditary [ATTRv], 70% wild-type [ATTRwt], 7% unspecified), and 8% unidentified subtypes. VE/VCO(2) slope was elevated across ATTR subgroups: 38.4 (95% CI: 36.9-40.0, I(2) = 57%) in ATTRwt and 37.9 (95% CI: 35.1-40.7, I(2) = 70%) in ATTRv. ATTR patients were older than AL patients by 9.0 years (95% CI: 0.4-17.6, I(2) = 88%) and had a higher VE/VCO(2) slope: 2.5 (95% CI: 0.2-4.8, I(2) = 0%). CPET modality influenced peak VO(2), which was lowest for treadmill exercise (13.7, 95% CI: 12.7-14.8, I(2) = 0%, mL/min/kg) compared to upright cycle ergometry (14.7, 95% CI: 14.3-15.1, I(2) = 33%) and semi-recumbent cycle ergometry (14.5, 95% CI: 14.1-14.9, I(2) = 28%). A high VE/VCO(2) slope characterizes both ATTRwt and ATTRv, while AL patients are younger with lower VE/VCO(2) slope levels. Peak VO(2) in ATTR patients may depend on exercise modality.