Study group. The study enrolled 77 CAD patients of both sexes, aged 30–80 years, who were candidates for phase II cardiac rehabilitation, and had undergone coronary angioplasty or coronary artery bypass grafting within 6 weeks prior to recruitment. The exclusion criteria were significant coronary artery stenosis; confirmed secondary hypertension; chronic kidney disease with the estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 calculated based on the MDRD equation; clinically important valvular heart disease; significant arrhythmias; non-sinus rhythm (including permanent pacemakers); body mass index (BMI) > 40 kg/m2; polyneuropathy; exercise-limiting peripheral artery disease and/or skeletal muscle disorders; psychiatric conditions preventing the patient’s full cooperation; and exacerbated lung conditions (asthma, chronic obstructive pulmonary disease (COPD)).
Clinical examination. The clinical examination included past medical history; drug history; current symptoms, particularly exercise tolerance (fatigue, dyspnea on exertion and at rest, chest pain); and smoking status. Physical examination included office measurements of heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP), and anthropometric measurements (height, weight, BMI). Laboratory tests were conducted on fasting peripheral venous blood samples collected in the morning (7:00–8:30 am), before CPET. The eGFR was calculated according to the MDRD equation.
Echocardiography. Echocardiographic examinations were conducted with a Vivid S6 ultrasound system (GE Medical System, Wauwatosa, WI, USA) following revascularization and no more than 6 weeks prior to recruitment. The examination included standard parasternal, apical, and subcostal views, and assessed cardiac chamber size, valvular structure and function, left ventricular ejection fraction (LVEF) measured via the Simpson method, diastolic function, and evidence of left ventricular hypertrophy. Heart failure (HF) was diagnosed based on current guidelines .
Cardiopulmonary exercise testing. Each patient underwent CPET in the morning, between 9:00 and 11:00 am, following the morning dose of their medications. An Ergoselect cycle ergometer (Geratherm Respiratory GmbH; Germany) was used, with individualized ramp protocols set to achieve the predicted load within 10 min. Oxygen and carbon dioxide sensors and the flow sensor (Ergoflow, Geratherm Respiratory GmbH; Germany) were calibrated before each test. Prior to CPET, each patient underwent resting spirometry. Each patient underwent maximum CPET, which was stopped if severe symptoms (fatigue, dyspnea) appeared or at the patient’s request . Throughout each CPET session, breath-by-breath gas exchange was monitored via a Geratherm Ergostik system (Geratherm Respiratory GmbH; Germany). The following parameters were analyzed: VO2 [mL/kg/min], workload [W], O2Pulse [mL/min], relationship between oxygen uptake and work rate (VO2/WR) [mL/min/W], ventilatory efficiency (ventilation-to-carbon dioxide output, VE/VCO2slope) during exercise, respiratory exchange ratio (RER). These parameters were analyzed at rest prior to CPET, at the anaerobic threshold (AT) and at peakVO2. PeakVO2 was expressed as the highest mean oxygen consumption over the last 30 seconds of exercise. The AT was determined noninvasively, with the V-slope method after CPET conclusion . Workload, VO2 and O2Pulse were expressed as percentage of their respective predicted values at peak exercise [peak % pred]. The predicted value of VO2 (pred VO2) was estimated based on Wasserman’s equation. . VE/VCO2slope was calculated with a regression formula Microsoft Excel. O2Pulse was calculated as the quotient of VO2 and HR. The changes in VO2 (ΔVO2) between the value at rest and both at AT and at peak exercise (peak–rest, peak–AT) were calculated. The RER, defined as VCO2/VO2, represented the highest mean value from the last 30 seconds during the final stage of CPET.
Exercise impedance cardiography. Exercise ICG was conducted with the use of a PhysioFlow monitor (Manatec, Paris, France). The methods employed during ICG were described in our earlier paper . The device offered beat-to-beat acquisition of the following parameters: HR [bpm], SV [mL], CO [mL/min], and left cardiac work index (LCWi [kg∙m/m2]), with the last one defined as the estimated energy requirement of the left ventricle to eject blood against the aortic pressure. As it was done in the case of CPET parameters, we calculated the changes in these parameters between their values at rest and both at AT and peak exercise (peak–rest, peak–AT).
Statistical analysis. Obtained results were analyzed statistically with Statistica 12.0 software (StatSoft Inc., Tulsa, OK, USA). Data distribution and normality were assessed visually and with the Kolmogorov-Smirnov test. Continuous variables were presented as means ± standard deviation (SD), whereas qualitative variables were presented as absolute and relative frequencies (percentages). Relationships between absolute LVEF, VO2, and hemodynamic parameters at AT and at peak exercise on one side and the changes in the analyzed exercise parameters (peak–rest, peak–AT) on the other were analyzed with Pearson/Spearman’s correlation coefficients. The p-value of < 0.05 was considered statistically significant.