A novel method to classify exercise response in patients with cardiac amyloidosis - The RoMa classification

Aims: To evaluate the applicability of the RoMa classification in patients with transthyretin cardiac amyloidosis (ATTR-CM) and to assess its association with functional capacity and key cardiopulmonary exercise testing (CPET) parameters. Methods: Consecutive adults (≥18 years) with confirmed ATTR-CM from two tertiary centres who completed symptom-limited maximal CPET were included. RoMa classes were defined using predefined cutoffs for percent-predicted peak heart rate (HRpp ≥80%) and percent-predicted peak O2-pulse (O2pp ≥100%): RoMa I (high HRpp/high O2pp), RoMa II (high HRpp/low O2pp), RoMa III (low HRpp/high O2pp), and RoMa IV (low HRpp/low O2pp). Results: We evaluated 165 patients (90% male; 77% wild-type ATTR, 20% variant ATTR). RoMa distribution was: RoMa I, n=33; RoMa II, n=73; RoMa III, n=30; and RoMa IV, n=29. Age did not differ across classes (p=0.36). Functional capacity declined across the RoMa strata: median 6MWD decreased from 420 m (RoMa I) to 313 m (RoMa IV) (overall p=0.009; p-trend=0.005), and NYHA class worsened (overall p=0.003; p-trend=0.005). Peak VO2 (% predicted) differed between groups (RoMa I: 93.0; II: 70.8; III: 75.2; IV: 51.9; overall p<0.001; p-trend<0.001), and ventilatory inefficiency increased (VE/VCO2 slope: 34; 39; 37; 47, respectively; overall p<0.001; p-trend<0.001; peak PetCO2: 30; 27; 29; 25, respectively; overall p<0.001; p-trend=0.003). 6MWD correlated with peak VO2 (r=0.626; p<0.001; n=131) and inversely with VE/VCO2 slope (ρ=-0.484; p<0.001; n=130). Conclusion: In ATTR-CM, application of the RoMa classification was feasible and identified distinct CPET-derived exercise-response profiles associated with functional impairment. These findings support RoMa as a promising exploratory framework for functional phenotyping in ATTR-CM.