All patients were referred for a multi-disciplinary secondary prevention program at the Cardiovascular Prevention and Rehabilitation Center (EPIC Center) of the Montreal Heart Institute and included in a randomized training intervention study. Details on the inclusion and exclusion criteria have been previously described elsewhere.22,23 Essentially, all CHD patients were under optimal medical therapy following coronary revascularization for ACS. Patients had to be stable with regard to symptoms and medication doses during the 4 weeks prior to enrolment. For this analysis, data from 2 prospective randomized exercise-intervention studies were pooled. The first study comprised post-ACS patients who were randomized (1:1) to either LV-HIIT or MICET. The primary endpoint was VO2peak. In the second pilot study, post-ACS patients were randomized (1:1) to either LV-HIIT or usual care, with lymphocyte GRK2 mRNA levels as the primary endpoint. This explains the disproportionate number of patients randomized in each group (LV-HIIT, MICET, usual care). The study protocols were approved by the Research Ethics and New Technology Development Committee of the Montreal Heart Institute. Both studies were registered on ClinicalTrials.gov (ClinicalTrials.gov identifier numbers: NCT03414996 and NCT02048696). Written informed consent was obtained by each patient.

Baseline clinical data, and CPET were assessed at baseline and after completion of the program. Baseline clinical data assessment included data on personal medical history, event details, and cardiovascular risk factor profile.

Maximal CPET was performed on a cycle ergometer (Ergoline 800S, Bitz, Germany) according to the recommendations of the American Heart Association, and as previously published.19,21,24,25 Following a 3-minute warm-up phase at an initial workload of 20W, an incremental exercise test was performed with 15 Watt increments per minute until exhaustion at a pedaling speed >60rpm. The recovery phase consisted of 2minutes of active recovery at 20W at pedaling speed between 50rpm and 60rpm, followed by 3minutes of passive recovery. Gas exchange parameters were continuously measured at rest, during exercise, and during recovery using a metabolic system (Oxycon Pro, CareFusion, Jaeger, Germany) as recently published.19,21,25 There was continuous ECG monitoring (Marquette, case 12, St. Louis, Missouri, USA). Blood pressure and rate of perceived exertion were measured every 3minutes throughout the test. The highest VO2 value reached during the exercise phase was considered as the VO2peak and peak workload was defined as the workload reached at the last fully completed stage. Oxygen uptake efficiency slope, ventilatory efficiency (VE/VCO2) slope, and ΔVO2/Δworkload slope were calculated according to recent recommendations.26

All patients performed 2 to 3 exercise training sessions a week on a bicycle ergometer. The aerobic exercise training consisted of 2 different training modalities: low-volume high-intensity interval training (LV-HIIT) or moderate-intensity continuous exercise training (MICET), which were isocaloric according to previously published methods.21 Additional resistance training was performed following each aerobic exercise session. All training was center-based and performed under the supervision of a certified kinesiologist.

The HIIT protocol was evaluated in a prospective randomized trial and optimized in that specific population (ie, CHD patients) as recently published.19,21 Following a 5-minute warm-up at 30% of peak workload obtained at the CPET, patients performed 2 to 3 sets of 6 to 10minutes with repeated bouts of 15 to 30seconds at 100% of peak workload alternating with 15 to 30seconds of passive recovery. The target rating of perceived exertion (rate of perceived exertion 6-20) was set at 15 during the HIIT bouts. The sets were separated by a 5-minute active recovery phase at 30% of peak workload. The training session was terminated by a 5-minute cool-down phase at 30% of peak workload (figure 1).27 The term low-volume refers to the fact that the weekly training volume with the protocols used was <150minutes (MICET) or <75minutes (LV-HIIT) for high/vigorous intensity, which are the minimal thresholds recommended by most international guidelines.28,29

Figure 1.

LV-HIIT and MICET protocol. LV-HIIT, low-volume high-intensity interval training; MICET, moderate-intensity continuous exercise training.

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Following a 5-minute warm-up at 30% of peak workload, patients performed continuous exercise at 60% of peak workload for 24minutes. At the end of the session, the patients performed 5minutes of recovery at 30% of peak workload (figure 1). The total time was 34minutes and the training was isocaloric with the LV-HIIT session.21 A recent meta-analysis in CHD patients underlined the importance of matching energy expenditure during the training when comparing exercise modalities (HIIT vs MICET).17 Indeed, the superiority of HIIT vs MICET on VO2peak improvement disappears when both protocols are isocaloric.17 Our isocaloric calculation method was strongly based on a direct measure of metabolic energy expenditure with gas exchange (VO2 uptake) during similar acute HIIT and MICET protocols in CHD patients.21

Resistance training consisted of 20minutes of circuit weight training performed with elastic bands and free weights adapted to each patient's capacity. For each muscle group, patients performed 1 set of 15 to 20 repetitions, followed by a 30-second rest at a target rate of perceived exertion of 15.27

The control group received recommendations on physical activity for a period of 12 weeks by their discharging cardiologist. If there were no recommendations at discharge, physical activity recommendations consistent with recent guidelines were given. Patients were encouraged to take 30 to 60minutes of moderate-intensity exercise at least 5 days per week (target rate of perceived exertion of 12-14).30

Data are presented as mean±standard deviation or median±interquartile range as appropriate for continuous variables, while frequencies and percentages are presented for categorical variables. Baseline characteristics were compared between the 3 groups using 1-way ANOVA and categorical variables were compared using the chi-square or Fisher exact tests. Repeated measures ANOVA models were used to study the CPET parameters across time and between groups. Models with time, group and group × time interaction as independent variables were used. The main focus of the analysis was the group × time interaction as it tested the difference in the change (post-pre) between the 3 groups. In addition, under the repeated measures ANOVA model, the change (post-pre) within each group was formally tested against zero. For the analysis of training response, VO2peak high response vs NLR was defined as the median value for change in peak oxygen uptake (ΔVO2peak in mL/min/kg) post- and pretraining in the whole cohort.8 Training response with a ΔVO2peak <2.1mL/min/kg was defined as NLR, while a ΔVO2peak >2.1mL/min/kg was defined as VO2peak high response. Univariate and multivariate logistic regression was used to generate a predictive model for training NLR. Predictors of training NLR for univariate logistic regression were selected as follows: sex, age, VO2peak percent predicted at baseline, presence of type 2 diabetes mellitus, and training modality. All analyses were performed with SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and conducted at the .05 significance level.

The study flowchart is presented in figure 2. In the final analysis, we included a total of 50 patients (LV-HIIT, n=23, MICET, n=18, usual care, n=9). Patients in the HIIT group tended to have lower body mass and lean body mass than patients in the MICET and usual care group. Otherwise, there were no differences with regards to baseline clinical characteristics (table 1).

Figure 2.

Flowchart of the study. ACS, acute coronary syndrome; Afib, atrial fibrillation; COPD, chronic obstructive pulmonary disease; CPET, cardiopulmonary exercise test; LV-HIIT, low-volume high-intensity interval training: MICET, moderate-intensity continuous exercise training.

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The median value for ΔVO2peak (in mL/min/kg) post and pretraining in the whole cohort was 2.1mL/min/kg. MICET was associated with a significantly lower proportion of training NLR compared with LV-HIIT and usual care (21% in MICET, 61% in LV-HIIT, and 80% in the usual care group; P=.004). Of note, for the LV-HIIT and MICET program, adherence (percentage) was defined as the number of attended sessions divided by the total planned sessions × 100. Patients were only included in the analysis if they attended at least 75% of the training sessions and 1.5 weekly training sessions. Patients completed 2.4±0.5 and 2.4±0.4 weekly training sessions in the LV-HIIT and MICET groups, respectively (P=.946). Weekly training duration was 83±12minutes with LV-HIIT and 80±14minutes with MICET (P=.487). Adherence was 100 (97) in the LV-HIIT and 100 (95) in the MICET group, respectively (P=.456).

As shown in table 2, VO2peak (normalized for body mass and lean body mass, respectively), predicted VO2peak, and peak workload (absolute and normalized for lean body mass) improved with training in the LV-HIIT and in the MICET group (P <.05 for time), while there was no effect in the usual care group. Significant group × time interaction was observed for these parameters (P <.05). The oxygen uptake efficiency slope and O2 pulse improved with LV-HIIT and MICET (P <.05 for time), but not in the usual care group. Moreover, the ΔVO2/Δworkload slope increased only in the MICET group (P <.05 for time), while there was no change in the LV-HIIT and the usual care groups. There was a significant group × time interaction for this variable (P <.05). In table 3, initial fitness (expressed as percent-predicted VO2peak) was not related to training NLR either in the univariate or in the multivariate analysis. In the multivariate regression model, age remained a predictor of training NLR (P <.05), while there was a trend for LV-HIIT vs MICET (P=.054).

In our study, data from 2 prospective randomized control trials were pooled for analysis from a single institution and with the participants composed mainly of men. This explains why a disproportionate number of patients were randomized to the 3 groups. This might have affected our results. However, a carefully selected and highly homogenous population of patients who experienced an ACS in the preceding 6 weeks before inclusion were included and randomized to either HIIT vs MICET or HIIT vs usual care. While our optimized LV-HIIT protocol has been well evaluated regarding the acute responses in CHD patients,19,21 our protocol is not the most commonly used in clinical research in patients with a recent ACS.17,31,35 Therefore, the results of our findings cannot be generalized, particularly not to a cohort using a different HIIT protocol.