Abstract

Introduction: The cardiopulmonary exercise testing (CPET) has been proved to be a good tool in prognostic stratification of HFrEF and HFpEF, but its value in cardiac amyloidosis (CA) is uncertain. With the increasing knowledge and clinical suspicion toward CA, the growing prevalence of the disease, and the current availability of disease-modifying drugs, prognostic stratification is becoming fundamental to optimise the cost-effectiveness of treatment, patient follow-up and management. Hypothesis: We investigate the association of VO2max and VE/VCO2 slope with prognosis in patients with CA. Methods: We performed a systematic review following the PRISMA guidelines. Electronic databases (MEDLINE, Biomed Central, and Cochrane Library) were searched for clinical trials performing CPET for prognostication in transthyretin and light-chain CA patients. Studies reporting Hazard Ratio (HR) for mortality and VO2 max or VE/VCO2 slope (1-unit increase) were further selected for quantitative analysis. After logarithmic transformation, HRs were pooled using a random-effect model. Results: Five studies were selected for qualitative analysis and 3 for the quantitative analysis. A total of 233 patients were included in the meta-analysis, 127 (55%) with transthyretin and 106 (45%) with light-chain CA. Mean VO2 max in each trial was consistently depressed, ranging from a mean of 14.5 ± 4.5 mL/kg/min to 15.2 ± 10 mL/kg/min. On the other side, the VE/VCO2 slope ranged from a mean of 30 ± 3.0% to 41.3 ± 9.7%. Our pooled analysis shows that VO2 max (pooled HR 0.89, 95%CI 0.84-0.94) and VE/VCO2 slope (pooled HR 1.04, 95%CI 1.01-1.07) are 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.

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