Changes in Exercise Tolerance over Time in Patients with Transthyretin Amyloidosis Cardiomyopathy Treated with Tafamidis

Abstract

Tafamidis improves the prognosis of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM). Additionally, it delays the decline in exercise tolerance, as observed in the six-minute walking test. However, the changes in cardiopulmonary function over time based on cardiopulmonary exercise tests are unclear. Thus, this preliminary study investigated the changes in exercise tolerance after one year of tafamidis treatment using cardiopulmonary exercise testing. Eight patients with ATTR-CM (average age: 77 years; male: n = 7) underwent cardiopulmonary exercise testing at baseline and after one year of tafamidis treatment. All eight patients completed a one-year follow-up. At baseline, the anaerobic threshold oxygen uptake (AT !O2: 10.9 ± 1.5) and peak !O2 (14.3 ± 3.0 mL/kg/minute) indicated relatively favorable exercise capacity; however, the minute ventilation/ carbon dioxide production ( !E/!CO2 slope), which indicates effective ventilation, showed poor performance (33.7 ± 12.8). One year after tafamidis treatment, frailty, as assessed by the Clinical Frailty Scale, had progressed in seven of eight patients (88%) (P < 0.01), and AT !O2 and peak !O2 were significantly reduced (19.2% and 22.3%, respectively; P < 0.05). The !E/!CO2 slope and peak O2 pulse decreased nonsignificantly by approximately 20% (P = 0.47, and P = 0.16, respectively). Further, the structure of the ventricles and atrium and the left ventricle ejection fraction on echocardiography did not change. Thus, exercise tolerance in patients with ATTR-CM was reduced after one year despite tafamidis administration. Not only ATTR-CM progression, but also frailty progression may influence this decrease in exercise tolerance. A comprehensive approach, including tafamidis administration and cardiac rehabilitation, is required for further improvement in the exercise capacity of patients with ATTR-CM.

(Non)-Exertional Variables of Cardiopulmonary Exercise Testing in Heart Failure with and Without Cardiac Amyloidosis

“…Prognosis of CA is limited and has been shown by a retrospective study with wtATTR amyloidosis patients treated with Tafamidis, in which one-third of patients fulfilled the composite primary outcome of mortality, heart transplant, and palliative inotrope initiation after a 1-year follow-up [ 23 •]: low VO 2peak , CP, and O 2 pulse max were associated with the primary outcome. In addition, it has been shown that O 2 pulse max and VE/VCO 2 decline over time in CA [ 24 ]. The importance of early diagnosis at a better functional state was recently shown by demonstrating that baseline VO 2peak > 14 ml/kg/min and VE/VCO 2 ≤ 34 were associated with a lower risk of death or heart failure rehospitalization before initiation of Tafamidis treatment ( n = 54, 9 ± 3 months follow-up, mean age 78 ± 6 years, LVEF 52 ± 11) [ 25 ].…”

“…It must be noted that a single CPET variable cannot be used to discriminate the underlying organ dysfunction. As CA and HF have been shown to be limited not only by peak performance induced through the progression of cardiac disease itself but also by reduced muscle capacity [ 37 , 38 ] and progression of frailty [ 24 ], CA itself needs to be regarded as a systemic rather than a mere cardiac disease. Thus, diagnostic workup of CA requires the incorporation of different modalities, such as imaging, CPET, and laboratory markers.…”