Serial changes in CPET parameters in untreated patients with transthyretin cardiac amyloidosis

Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is associated with a progressive reduction of functional capacity. The progression of cardiopulmonary exercise testing (CPET) parameters over time is still unknown. Methods: In this study 55 patients with ATTR-CM underwent two serial cardiological evaluation and CPET in a National Referral Center for cardiac amyloidosis (Careggi University hospital, Florence). Results: Forty-three patients (78%) had wild type ATTR. Median age was 80 (76-83) years, 50 patients (91%) were men. At baseline median peak oxygen consumption (pVO2) was 15 (12-18) ml/kg/min, percentage of predicted pVO2 (%ppVO2) was 71 (60-83) % and VE/VCO2 slope was 31 (26-34). After a median follow-up of 14 (13-16) months, pVO2, %ppVO2 and VE/VCO2 slope were significantly worsened (-1.29ml/kg/min, CI -1.85 to -0.74, p<0.01, -4.5% CI -6.9 to -2.02, p<0.01, 8.6 CI 6 to 11, p<0.01, respectively). Furthermore, exercise time (-39 seconds, CI -59 to -19, p<0.01), exercise tolerance (-0.47 METs, CI -0.69 to -0.2, p<0.01) and peak systolic pressure (-10.8 mmHg, CI -16.2 to -5.4, p<0.01) were significantly reduced. The worsening in CPET variables did not correspond to a significant change in echocardiographic parameters. Conclusions: Cardiorespiratory response to exercise significantly worsened over a short period of time in patients with ATTR-CM. Serial CPET may be useful to identify early disease progression.