Exercise-based cardiac rehabilitation (CR) is a secondary prevention tool used worldwide to improve physical function and prognosis in patients after myocardial infarction (MI) (1, 2). High-intensity interval training (HIIT) has recently emerged as an alternative or adjunct strategy to traditional moderate-intensity continuous training (3). HIIT involves alternating periods ranging from a few seconds to 4 min of higher intensity exercise [high-intensity intervals, HIIs: 85 to 95% of peak heart rate (HR) corresponding to 75 to 85% of peak oxygen uptake (V˙O₂)] with 1 to 4 min of lower intensity exercise (low-intensity intervals, LIIs: <60% of peak HR) during an exercise session (4). HIIT has been shown to result in similar or greater improvements in aerobic capacity and other health outcomes compared to moderate-intensity continuous training (4). However, the relationships between patient safety, perception of effort, and cardiorespiratory responses and adaptations during HIIT sessions in patients after MI have not been reported. Gaps in our understanding of the relationship between effort perception and cardiorespiratory responses limit our ability to provide optimal guidance for prescription, implementation, and safety of HIIT in CR.

The most common metrics to prescribe aerobic exercise intensity during CR include V˙O₂, HR, and their derivative indicators such as percentages of predicted/peak HR and V˙O₂; reserves of HR and V˙O₂; and metabolic equivalents (METs) (5). During outpatient CR, continuous monitoring of V˙O₂ is impractical and, while continuous HR monitoring is feasible, the high number of MI patients prescribed rate modulating pharmacotherapy (e.g., beta-blockers) makes HR a highly variable metric for exercise prescription (6). Furthermore, many patients who begin CR have not performed a graded exercise test, and peak HR has not been determined (7). For these patients, prescribing exercise intensity using predicted peak HR as a guide is imprecise.

Ratings of perceived exertion (RPE) are a practical alternative for prescribing exercise intensity and facilitates relative patient autonomy and progression of exercise intensity during CR (4, 8). Our CR program has used RPE, accompanied by continuous HR and periodic blood pressure monitoring, to prescribe exercise intensity for several decades (9, 10). Our CR staff are experienced in instructing patients on the proper use of the 6–20 Borg RPE scale. Patients are carefully instructed on the use of RPE as part of their baseline graded exercise test and during their first supervised exercise session in CR (10). We have previously demonstrated that RPE-prescribed HIIT improves body composition, characteristics of metabolic syndrome, and cardiorespiratory fitness in patients after MI (11, 12). However, the cardiorespiratory responses directly measured with metabolic gas exchange during, and adaptations to HIIT across several exercise sessions in MI patients have not been previously reported.

Therefore, this study aimed to determine the cardiorespiratory responses and adaptations during HIIT exercise sessions prescribed using RPE in patients with MI who participate in early outpatient CR. We hypothesized that: (1) Using RPE to prescribe exercise intensity will effectively elicit a desired HIIT cardiorespiratory response, and (2) RPE-based HIIT will result in an increasing V˙O₂ during exercise training across exercise sessions without increased perception of effort or excessive increases in heart rate and blood pressure.

Patients' demographic and clinical characteristics are shown in Table 1. Among the 11 patients, four suffered ST-segment elevation MI, and seven suffered non-ST-segment elevation MI; two patients underwent double-vessel PCI, and nine performed single-vessel PCI. The interval between the hospital dismissal and the start of outpatient CR was 14 [4] [median (IQR)] days. Pre CR echocardiograms demonstrated normal left ventricular systolic function with left ventricular ejection fractions of 56% [6%] [median (IQR)]. Echocardiography was not repeated after CR.

Exercise workload and cardiorespiratory responses to RPE prescribed HIIT are presented in Figure 1 and Table 2. The highest mean V˙O₂ during HIIs of 88 sessions of HIITs [91 (14)% of V˙O_2peak, median (IQR)] was significantly higher than for the target V˙O₂ (75% of V˙O_2peak) recommended for HIIs (p < 0.001). The ICC of exercise intensity, %V˙O_2peak, between the RPE-prescribed HIIT sessions was 0.95 (95% CI, 0.86 to 0.99, p < 0.001). The values of treadmill speed, treadmill grade, power, V˙O₂, %V˙O_2peak, HR, %HR_peak, SBP, V_E, V_T and f_B in the HIIs were significantly greater than those in the LIIs during each exercise session (all p < 0.01), which was consistent with the values of RPE during the HIIs vs. during the LIIs [15 (2) vs. 11 (2), median (IQR), p < 0.001]. A difference of 9–11% between %HR_peak and %V˙O_2peak was present for the LIIs and is consistent with conventional wisdom as reported in the literature (16) that %HR_peak is greater than %V˙O_2peak at a constant workrate. However, for the HIIs, %HR_peak was not higher than %V˙O_2peak. For the HIIs of the first HIIT session, median %HR_peak and %V˙O_2peak were identical (88%), while for the final session %V˙O_2peak was greater than %HR_peak (97% vs. 90%) during HIIs. No differences were found in DBP and RER between HIIs and LIIs (all p > 0.05).

Comparisons of the first vs. the last exercise sessions to assess cardiorespiratory adaptations during RPE-prescribed HIIT are presented in Table 2 and Figure 2. No differences were found for RPE, HR, %HR_peak, V_T, f_B, V_E/VCO₂, SBP and DBP (all p > 0.05) between the first and last session for both HIIs and LIIs. However, treadmill speed, treadmill grade, power, V˙O₂, %V˙O_2peak, EE per minute and per session and V_E increased significantly from the first to the last session for the HIIs (all p < 0.05), while no changes were detected for the LIIs (all p > 0.05). No adverse events related to exercise training occurred during the study.

Body mass significantly decreased [98.1 (22.6) kg vs. 95.0 (11.0) kg, median (IQR)] with a mean decrease of 3.1 [95% CI, 0.5 to 5.7] kg (p = 0.02). Peak cardiorespiratory variables were determined via CPETs at the beginning and end of CR. V˙O_2peak independent of body mass was not significantly different from pre- to post-CR [2.4 (0.6) L·min⁻¹ vs. 2.5 (0.7) L·min⁻¹, median (IQR)] with a mean difference of 0.1 [95% CI, −0.1 to 0.3] L·min⁻¹ (p = 0.21). However, V˙O_2peak dependent on body mass increased in nine of 11 subjects. V˙O_2peak relative to body mass increased [24.0 (6.5) ml·kg⁻¹·min⁻¹ vs. 26.1 (8.0) ml·kg⁻¹·min⁻¹, median (IQR)] with a mean increase of 1.9 [95% CI, 0.1 to 3.8] ml·kg⁻¹·min⁻¹ (p = 0.049). In addition, V˙O_2peak as a percentage of age, sex, and anthropometrically predicted values significantly increased from pre- to post-CR [95 (28)% vs. 100 (25)%, median (IQR)] with a mean difference of 5 [95% CI, 1 to 10] % (p = 0.04). No additional significant differences were detected in peak exercise cardiorespiratory variables pre-and post-CR.

Our study provided unique metabolic gas exchange data obtained during HIIT sessions and established the efficacy of using self-selected exercise intensity based on a target RPE range as a safe and practical method of prescribing HIIT for patients after MI during early outpatient CR. Our method of prescribing 5–8 one minute HIIs with RPE 14–17 interspersed with 4-min LIIs (RPE < 12) during a 40-min session of training was effective in eliciting a V˙O₂ of >95% of pre-training V˙O_2peak during the final HIIT session.

We demonstrated that over 8 weeks of HIIT, patients were able to exercise at a higher V˙O₂ without a concurrent increase in RPE or excessive HR and blood pressure response. Patients were able to increase the rate of energy expenditure during the HIIT sessions without an increased perception of effort which is potentially clinically important for decreasing body fat stores with the attendant metabolic health benefits.

Aamot et al. (17) reported that using RPE to prescribe exercise intensity during HIIT resulted in a lower than expected intensity based on %HR_peak, (detected 82% HR_peak vs expected 85% HR_peak) during HIIs (18) in patients with coronary artery disease in which 80% patients regularly used beta-blockers. In our study, we utilized both %V˙O_2peak (gold standard to reflect exercise intensity) and %HR_peak to assess the validity of RPE-prescribed HIIT. Both %V˙O_2peak and %HR_peak achieved during HIIs were more than the required levels to meet the designation of high-intensity (75% V˙O_2peak and 85% HR_peak) for all sessions. V˙O_2HII increased from 88% of V˙O_2peak in the first HIIT session to 97% of V˙O_2peak in the last session.

Patient progression in exercise training dose without the sacrifice of safety is a core tenet of cardiac rehabilitation. We observed that despite an increased V˙O_2HII across exercise sessions, no significant increases in HR, DBP, SBP, or perception of effort were found during RPE-prescribed HIIT. The underlying reasons for this remain unclear. V˙O₂ is an integrated indicator of the systems that transport and utilize oxygen, including the respiratory (oxygen uptake from the atmosphere), heart (oxygen transport), peripheral vasculature (oxygen transport, tissue perfusion, tissue diffusion), and skeletal muscle (oxygen extraction and utilization) (19, 20). In the present study, HR, O₂ pulse [a surrogate for stroke volume (21)], V_E/VCO₂ [an indicator of ventilatory efficiency (22)], RER (a variable to reflect degree of exertion) were not significantly changed during 8 weeks of RPE-prescribed HIIT sessions, which suggests that peripheral vasculature and skeletal muscle adaptations may have contributed to the increase in V˙O_2HII across sessions. This hypothesis is supported by our pre-clinical studies in mice that demonstrated regular exercise improved the structure and function of the aortic endothelium (23) and mitochondria in skeletal muscle (24, 25). However, additional research on the mechanisms responsible for these observations is needed.

In order to evaluate the cardiopulmonary adaptations during 8 weeks of HIIT sessions., we studied the relationship between %V˙O_2peak and %HR_peak during the HIIT sessions. During LIIs, the values for %V˙O_2peak were 61% for both first and last sessions, and the corresponding %HR_peak values were 70 and 72%, respectively. This is consistent with previous reports, where %HR_peak was ~10% higher than %V˙O_2peak (26). However, during HIIs, the %V˙O_2peak was 88% for the first session and 97% for the last session, while the corresponding %HR_peak remained ~90% for both sessions. This is a clear disconnect from the assumed relationship of %V˙O_2peak and %HR_peak. Though it has been assumed that the %HR_peak-%V˙O_2peak relationship holds during HIIT, the expected linear relationship between %V˙O_2peak and %HR_peak was established during graded exercise testing with cardiopulmonary measurements and may differ during HIIT. Further studies are needed to elucidate the mechanisms responsible for these observations.

The effect of HIIT on cardiorespiratory fitness in patients with coronary artery disease has been reported, with mean V˙O_2peak increases ranging from 11 to 25% (4). A recent study from our group demonstrated that RPE-prescribed HIIT during early outpatient CR significantly improved V˙O_2peak by 18% (pre-CR vs. post-CR, 23.0 ± 6.3 vs. 28.0 ± 5.9; mean change 5.0 ± 2.5 ml·kg⁻¹·min⁻¹) in 42 MI patients (12). In the present study, HIIT improved cardiorespiratory fitness (i.e., V˙O_2peak) in 9 of 11 (82%) patients, with a mean improvement of only 9%. Possibly related to the small sample size in the current study, statistically significant changes were found in V˙O_2peak related to body mass and % predicted V˙O_2peak, but not in V˙O_2peak independent of body mass. The percentage of non-improvement (non-responder: failure to improve V˙O_2peak) in CR was 18% in the present study, which is consistent with the data reported in the study by Savage et al. (27) in which 81 out of 385 patients (21%) failed to improve V˙O_2peak during outpatient CR using moderate-intensity continuous training. Our finding of non-improvement in V˙O_2peak with HIIT in some patients is a novel finding. Non-improvement in CR may be associated with exercise intensity, comorbidity score, self-reported physical function, diabetes, and baseline V˙O_2peak (27). In the present study, mean baseline V˙O_2peak was normal and may be a factor in our findings of a less than typical increase in V˙O_2peak and identification of non-responders with HIIT.

The present study did not assess change in left ventricular systolic or diastolic function resulting from HIIT. The literature suggested that HIIT is an effective strategy to attenuate left ventricular remodeling in clinically stable heart failure patients with reduced ejection fraction (28). The effect of HIIT on left ventricular function in heart failure with preserved ejection fraction is controversial (29), while the positive effects of HIIT on exercise capacity and quality of life in patients with MI and heart failure have been reported (4). The patients in the present study were not diagnosed with HFpEF. Further studies are warranted to investigate the effects of HIIT on cardiac function in patients after MI and heart failure with preserved ejection fraction.

Our study examined a single, unique HIIT protocol in MI patients and may not be generalizable to other methods of prescribing HIIT or to other clinical populations. Because measuring metabolic gas exchange data during multiple 30–40 min CR exercise sessions is technically and logistically challenging, we studied only a limited number of patients. Our patients' average baseline V˙O_2peak was in the normal range for healthy individuals and our subjects are not representative of typical post-MI patients. In addition, we did not compare RPE vs. HR-based prescriptions for HIIT. While RPE certainly appears to be an effective prescriptive tool for HIIT, it remains unknown if RPE is the optimal prescription method despite its previously discussed advantages. Additionally, the cardiorespiratory assessments made during HIIT did not include direct measures of cardiac function (e.g., echocardiogram) and relied on an indirect method for cardiac adaptations (i.e., V˙O₂ and V_E/VCO₂). As such, future studies should consider performing more comprehensive and direct measurements to identify the specific central and peripheral mechanisms responsible for the cardiorespiratory adaptations to RPE-prescribed HIIT in patients after MI.

RPE is an effective and safe method for prescribing HIIT for patients enrolled in early outpatient CR after uncomplicated MI. Using RPE eliminates reliance on heart rate for exercise intensity prescription and may be advantageous for patients who do not perform a pre-CR exercise test and for individuals receiving heart rate modulating medications. Using an RPE target of 14–17 during 1-min of high-intensity exercise elicits a robust V˙O_2HII of >90% of V˙O_2peak. The expected relationship between %HR_peak and %V˙O_2peak (%HR_peak > %V˙O_2peak) is not present during the HIIs of the HIIT. Patients are comfortable performing 5–8 one-minute intervals at >90% of V˙O_2peak during a 40-minute aerobic exercise session. Over the course of eight weeks of HIIT-based CR, patients increased treadmill speed and grade, and V˙O_2HII without an increase in perception of effort or excessive increases in heart rate and blood pressure.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Mayo Clinic Institutional Review Board. The patients/participants provided their written informed consent to participate in this study.

YD, RS, and TO are responsible for the conception and design of the work. YD, JS, and MM contributed to the acquisition or interpretation of the work. YD, SH, JS, BS, and SL drafted the manuscript. YD, SH, JS, MM, BS, RS, SL, and TO critically revised the manuscript, gave final approval and agree to be accountable for all aspects of the work ensuring integrity and accuracy. All authors have read and approved the final manuscript.

The present study was supported by grants from the National Institutes of Health (HL-126638 to TO; T32 HL-07111 to SH and JS; and K12 HD-065987 to JS), National Nature Science Foundation of China (82002403 to YD), Hunan Provincial Nature Science Foundation of China (2021JJ40981 to YD), and the Youth Science Foundation of Xiangya Hospital (2019Q03 to YD).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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