Evaluation of Incidence and Risk Factors of Sudden Cardiac Death in Patients with Chronic Coronary Syndrome Attending Physical Training

Patients and the Compounds of the Physical Training

A group of 135 patients with CCS were involved in this retrospective cohort study. Inclusion criteria were prior ACS treated by percutaneous coronary intervention (PCI) and/or acute coronary artery bypass graft surgery (CABG) or having a primary CABG surgery on the basis of CCS. All the patients have been treated immediately after the indexed cardiovascular event in an inpatient cardiac rehabilitation unit at the University of Pecs, Medical Centre, 1st Department of Medicine, Division of Preventive Cardiology and Rehabilitation. According to the guidelines [25], 3 months after the index event every patient has an extensive physical examination, echocardiography, and treadmill stress test performed by Bruce protocol. After checking the test results by a cardiologist, patients with no residual symptoms, normal clinical chemistry (normal potassium level, liver function, blood count, inflammation parameters, troponin), EF > 50%, MET > 5, no significant arrhythmia or ischemic sign on baseline ECG or during the treadmill test and in the recovery could enter the outpatient training program. Patients with an indication for implantable cardioverter defibrillator (ICD) implantation are excluded from the program; therefore, no patients with ICD were included and no ICD discharge occurred during the study. These inclusion criteria are responsible for the relatively good health of the patient group involved in the study. Subsequently, our recruited subjects participated in an outpatient cardiac rehabilitation program for a minimum of 1 month. This program involved 1-h sessions of physical training, held three times a week, and was designed and conducted by a physiotherapist under the supervision of a cardiologist. Patients were not obligatory to attend all training sessions through the entire observational period. Due to personal or working issues, other than health problems (i.e., new-onset of arrhythmia, heart failure, acute coronary event, etc.), our patients may left transitionally or permanently the training program.

The present aerobic exercise training program used in our cohort study was preceded and ended with blood pressure and pulse measurements. The patients began with warm-up exercises (breathing exercises, and stretching of the large joints) for 5–10 min. In the second phase, they participated in a moderate-intensity training. Intensity was defined as 50–70% of peak VO2 (starting at 50% and gradually increasing to 70% of VO2max). The intensity was assessed by the Borg scale (13–15/20) [26] and pulse measurements. The training involved static (exercises with medicine ball, half-squats, toe raises, body flexions) and dynamic (walking, jogging, ball games e.g., basketball, football) exercise elements. The aerobic phase lasted for 35–40 min. Finally, relaxation exercises were performed (stretching and breathing exercises) for 10 min.

Data Collection

Our cohort was created retrospectively by 135 patients on March 1, 2010, and was followed up until March 1, 2021. The morbidity and mortality data of the participants were collected with retrospective data mining using the e-MedSolution program, an integrated information system of the patient care at the University of Pecs.

We obtained the following demographical and morbidity data from our patients: age, sex, length of attending training and/or being absent from training, cardiovascular risk factors as smoking habits, baseline and output (at the time patients left the training program) body mass index (BMI), left ventricular ejection fraction (LVEF) and metabolic equivalent (MET). The ∆ values of BMI, LVEF and MET were calculated from baseline and output data (when patient left program permanently) [baseline-output/baseline] and used for further analyses. Based on the total number of training sessions within the observational period, patients with higher than 90% attendance at training sessions were considered as regular participants. In case of more than 10% absence, the participation was considered irregular. From a cardiovascular aspect, important comorbidities, i.e., hypertension, diabetes, chronic kidney disease (CKD), peripheral arterial disease (PAD), and the currently used CCS guideline recommended medications, meaning angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), beta-blockers (BBs), statins, platelet aggregation inhibitors (PAI) were also obtained.

The endpoint of the study was specified as SCD or SCA, where SCD was defined as mentioned above as a clinical death and SCA as an aborted case of SCD. The group that did not experience any SCD or SCA events was defined as the control group. The control study's endpoint was either the end of the observational period or death from a cause other than SCD/SCA. Patients in the SCA group received appropriate treatment and ICD implantation after the event. However, since these patients were unable to continue attending the program, the SCA event marked the endpoint of the study for them, and we did not collect further data for these patients.

The study was approved by the Regional Ethics Committee of the University of Pecs (9274 – PTE 2022.). The study was conducted according to the guidelines of the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study. We would like to thank the participants of the study.

Statistical Analysis

Differences were evaluated by IBM SPSS Statistics® 20.0. Significance level was defined as p < 0.05.

In case of continuous variables (age, training length of participation and absence, BMI, LVEF, MET) differences between SCD and SCA group and between SCD/SCA and control group were evaluated by a one-way repeated ANOVA statistical test after using the Kolmogorov–Smirnov test to check on the normality of the data distribution. Data are shown as mean ± SEM.

In case of categorical variables (sex, smoking, comorbidities, medication), associations between SCD and SCA group and between SCD/SCA and control group were determined by using chi-square test analyses. Data are shown as percentage and incidence (absolute number compared to total number).

Multinominal logistic regression and stepwise analysis of the data were performed considering the principle of multicollinearity (all independent variables have a variance inflation factor under 1,2) [27] to reveal occurrence of SCD/SCA using age, absent training months, ΔBMI, ΔLVEF, ΔMET, diabetes, CKD, smoking, taking ACEIs, ARBs, BBs, and statins as independent variables.

Cox regression models were created as time-to-event analyses regarding SCD/SCA event as dichotomous categorical outcome to compare independent variables age, sex, irregular training participation, CKD, BB, ΔLVEF, and smoking. Estimated hazard ratios and related 95% confidence intervals (CI) are shown.

Multinominal logistic regression and stepwise analysis of the data were performed considering the principle of multicollinearity (all independent variables have a variance inflation factor under 1,35) [27] to reveal occurrence of death between SCD and SCA subgroups using sex, attending and absent training months, taking ACEIs, ARBs, PAIs and statins as independent variables.

Cox regression models were created as time-to-event analyses regarding SCD and SCA uncensored event among SCD and SCA subgroups as dichotomous categorical outcome to compare independent variables sex, number of training months, and irregular training participation, taking BBs. Estimated hazard ratios and related 95% confidence intervals (CI) are shown.

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