Background: Cardiac rehabilitation (CR) is a comprehensive intervention recommended for patients with coronary artery disease (CAD) and chronic heart failure (HF). Metabolic impairment in HF involves an inability to properly utilize energy sources and a decline in mitochondrial function, affecting both the heart and peripheral muscles, also contributing to exercise intolerance. This study examined the oxidation of macronutrients assessed during cardiopulmonary exercise testing (CPET) as an indicator of mitochondrial capacity during CR in CAD patients with HF (CAD+HF) and without HF (CAD).
Methods: In this observational study, 132 CAD+HF patients (21% women, 55.2±7.2 years, BMI 29.9±5.3 kg/m²) and 326 CAD patients (24% women, 55.4±7.3 years, BMI 29.4±4.6 kg/m²; p≥0.328) were referred to 3-4 weeks of CR after myocardial infarction and/or reperfusion via percutaneous transluminal coronary angioplasty and/or coronary artery bypass graft and underwent CPET at admission and before discharge. Breath-by-breath spirometric data was used to calculate substrate oxidation rates for fatty acids (FatOx) and carbohydrates by stochiometric calculation. Data was then plotted as percentage of maximal exercise capacity. Mean area under the curve (AUC) for relative oxidation rates with 95% confidence interval as well as linear regression from start to peak was calculated. Maximal fat oxidation (MFO) was compared to published data from healthy controls.
Results: Patients were referred to CR with significant limitation in physical exercise capacity at peak exercise (CAD+HF, 17.7±4.1 ml/min/kg; CAD, 19.3±4.7 ml/min/kg; p<0.001). In CAD+HF patients, 77% exhibited slightly reduced (41-50%), 21% moderately reduced (31-40%) and 2% severely reduced LVEF (≤30%). Compared to healthy controls (MFO: 0.46±0.17 g/min), FatOx in CAD patients was significantly impaired (MFO: 0.32±0.15 g/min; p<0.001) with a mean AUC of 9.9[9.4-10.5]. CAD+HF patients exhibited comparable limitations at admission (MFO: 0.31±0.15 g/min; AUC: 9.2[8.7-9.6]; p≥0.140 vs. CAD), but showed significantly smaller improvements (+8.7%) compared to CAD patients (+15.6%). Of note, CAD+HF patients with moderately and severely reduced LVEF exhibited an improvement of 16.2% in FatOx, while CAD+HF patients with slightly reduced LVEF only improved by 6.6% in FatOx. CAD+HF and CAD exhibited a comparable prevalence of diabetes (18%; p=0.418) but differed with respect to SGLT-2 inhibitor use (CAD+HF, 34%; CAD, 9%; p<0.001). However, there was no benefit in improvement of FatOx in CAD+HF patients with SGLT-2 inhibitor therapy compared to patients without (+8.9% vs +8.4%). The observed differences in improvements were independent of age, sex, BMI and fat-free mass (p≥0.328). Carbohydrate oxidation was not impaired in CAD or CAD+HF patients.
Conclusion: CAD+HF patients demonstrated improved FatOx capacity likely linked to restored mitochondrial function in response to CR. Even if these improvements were smaller compared to CAD patients without HF, this is of relevance since reversing the metabolic impairment in CAD+HF patients by physical exercise may be an additional clinical benefit.
