Prognostic value of cardio-pulmonary exercise testing in cardiac amyloidosis

Background In amyloid patients, cardiac involvement worsens dramatically both functional capacity and prognosis. Purpose We sought to study how the cardio-pulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA). Methods We carried out a prospective multicenter study including both immunoglobulin light chain (AL) and transthyretin (TTR) cardiac amyloidosis patients. All patients underwent clinical examination, EKG, blood measurement of cardiac biomarkers, echocardiography, CPET and clinical follow-up. The primary prognostic endpoint was the occurrence of death or heart failure (HF) hospitalization. Results We included 150 patients: 91 AL and 59 TTR cardiac amyloidosis. Median age, systolic blood pressure, NT-proBNP and cardiac troponin T were 70 [64–78] years old, 121 [IQR 109–139] mmHg, 2809 [IQR 1218–4638] ng/L and 64 [IQR 33–120] ng/L respectively. NYHA classes were I–II in 64% and III in 36%. The mean peak VO2 was low at 13.0 mL/kg/min [10.0–16.9] i.e. 56% of predicted value; mean circulatory power was also impaired (1729 mmHg.mL−1min_1, IQR 1318–2614). The VE/VCO2 slope i.e. respiratory response was increased to 37 [IQR 33–45]. Seventy-seven patients (51%) had also severe chronotropic insufficiency. After a median follow-up of 20months, there were 37 deaths and 44 HF-related hospitalizations. Multivariate Cox analysis shows that peak VO2 (HR 2.7; CI 95% 1.6–4.8), circulatory power (HR 2.4; CI 95% 1.2–4.6) and NT-proBNP (HR 2.2, CI 95% 1.1–4.3) were independently associated with the primary outcome. There was no event in patients with both peak VO2 > 13 mL/kg/min and NTproBNP   1800 ng/L identified the subset at highest risk ( Fig. 1 ). Conclusion In CA, CPET helps to assess functional capacity, circulatory and chronotropic responses and helps to assess the prognosis of patients along with cardiac biomarkers.