Metabolic rehabilitation in patients with cardiovascular disease

Background Cardiac rehabilitation (CR) is a comprehensive intervention recommended for patients with coronary artery disease (CAD). While the effects of exercise-based rehabilitation on cardiorespiratory fitness and health-related quality of life are well established, its metabolic effects are less well explored. Purpose This study investigates fat oxidation (FatOx) during exercise as an indicator of mitochondrial capacity and its potential use as a marker of rehabilitation success in patients with CAD. Methods A total of 458 CAD patients (23% women, 55.3±7.3 years) following myocardial infarction and/or percutaneous transluminal coronary angioplasty underwent cardiopulmonary exercise testing at admission and before discharge of 3–4-week inpatient CR. Detailed breath-by-breath spiroergometric data were used to stoichiometrically determine substrate oxidation rates. Data were expressed relative to maximal oxygen uptake (VO2peak). Responder analyses were conducted for submaximal and maximal exercise capacity based on VO2 at ventilatory threshold 1 (VT1) and at VO2peak, as well as for maximal fat oxidation (MFO), using the typical-error method. MFO was compared with literature values from healthy controls. For subgroup analysis, the mean area under the curve (AUC) for FatOx with 95% CI and linear regression slopes from start to peak FatOx were calculated. Results Patients exhibited markedly reduced exercise capacity at submaximal (12.5±3.1 ml/min/kg; 57.4±19.8% of predicted reference) and peak exercise (18.8±4.6 ml/min/kg; 75.8±15.7% of predicted reference). FatOx was significantly impaired in CAD patients (MFO: 0.32±0.15 g/min; AUCpre: 9.7[9.2–10.2]) compared to healthy controls (MFO: 0.46±0.17 g/min; p<0.001). Subgroup analyses showed that impaired FatOx was particularly pronounced in women, patients with single-vessel disease, and those with prior myocardial infarction (AUC: 6.9[6.5–7.3], 8.6[8.1–9.1], and 9.0[8.6–9.5]). During rehabilitation, overall FatOx improved significantly (+14.3%; AUC: 11.1[10.6–11.7]; p<0.001), but improvements were smaller in women, older patients, and patients with reduced ejection fraction (+8.0%, +7.6%, and +8.7%). Men, younger patients, and those with normal ejection fraction (EF) showed greater improvements (+15.9%, +20.8%, and +15.6%). The responder analyses showed that 36% of patients improved in VO2@VT1, while 41% improved in VO2peak. Of note, 10% of patients showed no improvement in VO2@VT1 or VO2peak but demonstrated a significant large improvement in MFO (AUCpre: 8.4[7.9–8.9], AUCpost: 16.0[15.5–16.5]; +90.5%). Conclusion CAD patients demonstrated improved FatOx capacity in response to CR. Improvements were less-pronounced in women, older patients, and those with reduced EF. In addition to traditional outcome assessments based on VO2 uptake, MFO may be used to identify CR responders in terms of beneficial metabolic adaptations, potentially linked to restored mitochondrial function.