Cardiopulmonary exercise testing predicts prognosis in amyloid cardiomyopathy: a systematic review and meta‐analysis

BACKGROUND: The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current availability of disease‐modifying drugs, prognostic stratification is becoming fundamental to optimizing the cost‐effectiveness of treatment, patient phenotyping, follow‐up, and management. Peak VO(2) and VE/VCO(2) slope are currently the most studied CPET variables in clinical settings, and both demonstrate substantial, independent prognostic value in several cardiovascular diseases. We aim to study the association of peak VO(2) and VE/VCO(2) slope with prognosis in patients with CA. METHODS AND RESULTS: We performed a systematic review and searched for clinical studies performing CPET for prognostication in patients with transthyretin‐CA and light‐chain‐CA. Studies reporting hazard ratio (HR) for mortality and peak VO(2) or VE/VCO(2) slope were further selected for quantitative analysis. HRs were pooled using a random‐effect model. Five studies were selected for qualitative and three for quantitative analysis. A total of 233 patients were included in the meta‐analysis. Mean peak VO(2) resulted consistently depressed, and VE/VCO(2) slope was increased. Our pooled analysis showed peak VO(2) (pooled HR 0.89, 95% CI 0.84–0.94) and VE/VCO(2) slope (pooled HR 1.04, 95% CI 1.01–1.07) were significantly associated with the risk of death in CA patients, with no significant statistical heterogeneity for both analyses. CONCLUSIONS: CPET is a valuable tool for prognostic stratification in CA, identifying patients at increased risk of death. Large prospective clinical trials are needed to confirm this exploratory finding.