Optimizing Training Response for Women in Cardiac Rehabilitation: A Randomized Clinical Trial

Key Points

Question  For women in cardiac rehabilitation (CR), is high-intensity interval training (HIIT) along with lower extremity resistance training (RT) superior to standard moderate intensity training (MCT) for improving peak aerobic capacity (defined as peak oxygen uptake [peak Vo₂])?

Findings  In this randomized clinical trial including 56 patients, the HIIT group experienced significantly greater improvement in peak Vo₂ compared with the MCT group. No serious adverse events were reported.

Meaning  This study suggests that HIIT along with intensive RT may be an effective way for women in CR to increase peak Vo₂.

Importance  Despite lower baseline fitness levels, women in cardiac rehabilitation (CR) do not typically improve peak aerobic exercise capacity (defined as peak oxygen uptake [peak Vo₂]) compared with men in CR.

Objective  To evaluate the effect of high-intensity interval training (HIIT) and intensive lower extremity resistance training (RT) compared with standard moderate intensity continuous training (MCT) on peak Vo₂ among women in CR.

Design, Setting, and Participants  This randomized clinical trial conducted from July 2017 to February 2020 included women from a community-based cardiac rehabilitation program affiliated with a university hospital in Vermont. A total of 56 women (mean [SD] age, 65 [11] years; range 43-98 years) participating in CR enrolled in the study.

Interventions  MCT (70% to 85% of peak heart rate [HR]) with moderate intensive RT or HIIT (90% to 95% of peak HR) along with higher-intensity lower extremity RT 3 times per week over 12 weeks.

Main Outcomes and Measures  The primary outcome was the between-group difference in change in peak Vo₂ (L/min) from baseline to 12 weeks.

Results  Peak Vo₂ increased to a greater degree in the HIIT group (+23%) than in the control group (+7%) (mean [SD] increase, 0.3 [0.2] L/min vs 0.1 [0.2] L/min; P = .03). Similarly, the change in leg strength was greater in the HIIT-RT group compared with the control group (mean [SD] increase, 15.3 [0.3] kg vs 6.4 [1.1] kg; P = .004).

Conclusions and Relevance  An exercise protocol combining HIIT and intensive lower extremity RT enhanced exercise training response for women in CR compared with standard CR exercise training. Women randomized to HIIT experienced significantly greater improvements in both peak Vo₂ and leg strength during CR.

Trial Registration  ClinicalTrials.gov Identifier: NCT03438968

Peak aerobic exercise capacity, measured as peak oxygen uptake (peak Vo₂), is a powerful predictor of mortality among cardiac patients.¹ Despite having lower fitness at baseline, women generally do not improve peak Vo₂ as much as men in phase 2 cardiac rehabilitation (CR).^2,3 In a prior study of 1789 patients performing standard CR training, women improved by a mean (SD) 0.3 (0.4) L/min and men improved by a mean (SD) 0.4 (0.5) L/min (14% vs 19%, respectively).³

High-intensity interval training (HIIT) has been shown to be more effective in increasing peak Vo₂ compared with moderate intensity continuous training (MCT). However, benefits with HIIT for women are unclear because most studies of HIIT have included primarily men.^4,5 Additionally, resistance training (RT) alone has been shown to improve leg strength and walking endurance in older individuals.⁶ The purpose of this study is to examine the combination of HIIT and more intensive RT to maximize peak Vo₂ for women in CR. We hypothesized that increases in peak Vo₂ (L/min) would be greater among women performing HIIT and additional leg strength training compared with standard MCT.

This was a randomized clinical study performed from July 2017 to February 2020 and approved by the University of Vermont Institutional Review Board. A detailed protocol is available in Supplement 1. Written informed consent was obtained by all participants.

Women entering CR at a community-based cardiac rehabilitation program affiliated with a university hospital in Vermont and undergoing an exercise tolerance test with expired gas analysis were screened. Exclusion criteria included a peak Vo₂ less than 12 mL/kg⁻¹/min⁻¹, orthopedic limitations, exertional angina, complex arrhythmias, uncompensated heart failure, and submaximal performance on entry exercise tolerance test, defined as a respiratory exchange ratio less than 1.00. Fifty-six patients were enrolled, and 43 completed the protocol (Figure). Participants were randomized via computer-generated 1:1 assignments to either an isocaloric training regimen of MCT or HIIT combined with more intensive RT.

The HIIT group performed aerobic training exclusively on the treadmill. A 5-minute warm-up at 50% to 60% of peak HR was followed by four 4-minute intervals at 90% to 95% of peak HR. Each interval was followed by a 4-minute recovery period at 50% to 60% of peak HR. Treadmill speed and incline were adjusted to maintain the designated HR. The HIIT group exercised for 33 minutes followed by lower extremity RT, performing 2 sets of 10 repetitions at 80% of a single repetition maximal lift (1-RM) for leg press.⁷

The MCT group exercised at 70% to 85% of peak HR for 45 minutes total to maintain isocaloric training between groups. Exercise modalities included 25 minutes on the treadmill and 20 minutes on other ergometers, and a single set of 10 repetitions at 60% to 65% of 1-RM for leg press.⁸

Participants attended 3 supervised trainings per week. All were encouraged to exercise at moderate intensity on their own at least twice a week and were instructed to refrain from HIIT and RT outside of CR.

At entry, age, weight, body mass index (calculated as weight in kilograms divided by height in meters squared), comorbidities, and qualifying diagnosis were recorded. Because of its importance when assessing health care outcomes, we collected the data on race and ethnicity to characterize the study population. Participants self-reported race and ethnicity by free-form response. Handgrip strength using a hydraulic dynamometer and 1-RM for leg press were obtained.⁹ Exercise intensity (% peak HR) was measured midway through exercise for the MCT group and during the fourth interval for the HIIT group. A compliance of 95% CR attendance was used for completing the study.

Patients performed a symptom-limited treadmill exercise tolerance test until volitional exhaustion. To determine peak Vo₂ and peak respiratory exchange ratio, expired-gas analysis was measured continuously throughout with the Medgraphics Ultima metabolic cart. The highest average 30-second measure was used to define peak Vo₂.¹⁰ The workload performed on the last completed stage was defined as estimated peak metabolic equivalent of task.¹¹

Power calculations based on prior data with power of 0.8 at an α of .05 indicated a sample size of 22 per group was needed to detect a difference of 31% between groups in peak Vo₂.¹² Paired t tests and χ² were used for within- and between-group differences. To account for possible changes in weight during CR, absolute peak Vo₂ (L/min) was the primary outcome. Logistic regression analysis was performed to find a best fitting model predicting change in peak Vo₂ with the following independent variables: age, diagnosis, group assignment, diabetes, respiratory exchange ratio, handgrip strength, leg press 1-RM, peak HR, and percentage of target HR.

Factors associated with change in peak Vo₂ in the univariate logistic regression model at P < .05 were entered in a stepwise fashion into the multivariate model. Tests were 2-tailed and statistical significance was set at P < .05. Statistical analyses were performed using SAS version 9.0 (SAS Institute).

Baseline characteristics are listed in Table 1. Participant age ranged from 43 to 98 years, and the mean (SD) age was 65.2 (11.1) years. All self-identified as White. No differences were observed in clinical characteristics. Similarly, no differences were seen between individuals who dropped out vs those who completed the study (eTable in Supplement 2). No serious adverse events were reported. Two HIIT participants experienced aggravation of preexisting musculoskeletal injury.

Following CR completion, significant improvements in peak Vo₂, leg press, handgrip strength, and estimated peak metabolic equivalent of task were seen in both groups (Table 2). The MCT group lost significantly more weight than the HIIT group (mean [SD], 1.7 [1.3] kg vs 0.7 [1.2] kg; P = .02).

The HIIT group experienced significantly greater improvement (+23%) in peak Vo₂ compared with the MCT group (+7%) (mean [SD], 0.30 [0.17] L/min vs 0.13 [0.18] L/min; P = .03) (eFigure in Supplement 2). Additionally, the HIIT group had greater improvement in 1-RM for leg press compared with the MCT group (mean [SD], 15.3 [10.6] kg vs 6.4 [7.7] kg; P = .004).

Univariate correlates change in peak Vo₂ included age (adjusted R² = 0.11; P = .02), group assignment (adjusted R² = 0.10; P = .03), diagnosis (surgical vs nonsurgical; adjusted R² = 0.11; P = .02), respiratory exchange ratio at entry (adjusted R² = 0.10; P = .02), handgrip strength at exit (adjusted R² = 0.14; P = .01), leg press at entry (adjusted R² = 0.10; P = .04) and leg press at exit (adjusted R² = 0.10; P = .03), RPE at session 18 (adjusted R² = 0.11; P = .03), peak HR at session 36 (adjusted R² = 0.18; P = .01), and percentage of target HR at session 36 (adjusted R² = 0.08; P = .04). Independent predictors for change in peak Vo₂ included entry leg press and peak HR at session 36 (adjusted R² = 0.31; P < .001).

In this study, a combination of HIIT and more intensive RT increased peak Vo₂ to a greater degree than standard MCT in women. Given that changes in peak Vo₂ are associated with prognosis, a major goal of CR is to improve peak Vo₂.^1,13 Compared with men, women entering CR are on average older and have lower muscle strength.¹⁴ Isolated RT has been shown to increase strength and walking endurance in older adults.⁶ Furthermore, RT alone can improve peak Vo₂ in less fit individuals, thus highlighting the importance of higher-intensity RT in women.¹⁵

Prior studies have demonstrated that HIIT is significantly more effective than MCT in improving peak Vo₂.^5,12,13 However, these studies had few women and did not include RT. To our knowledge, this is the first female-only study to demonstrate the utility and efficacy of HIIT along with more intensive RT. Because baseline leg strength and intensity of exercise at session 36 were independent predictors of improvement of peak Vo₂, our results demonstrated that HIIT combined with intensive RT led to greater improvements in peak Vo₂. Although the study was not powered to test for safety of HIIT, it was well tolerated and warrants future surveillance.

This study had limitations, including the lack of racial and ethnic diversity and the single-center nature of the study. There was a nonsignificant difference in baseline peak Vo₂ between groups. Also, while all participants in both groups were encouraged to exercise on their own, we did not account for activity performed outside of CR.

Strengths of this study include that it is, to our knowledge, the first female-only study to examine the efficacy of combined HITT and intensive RT in CR and the use of directly measured peak Vo₂. Further, it is, to our knowledge, the first female-only study to examine the efficacy of combined HIIT and intensive RT in CR.

A combination of HIIT and higher-intensity RT results in greater improvements in peak Vo₂ compared with MCT with lower intensity RT. Our results suggest that, when appropriate, women should perform HIIT and intensive RT to maximize improvements in peak Vo₂ during CR.

Accepted for Publication: October 4, 2021.

Published Online: November 24, 2021. doi:10.1001/jamacardio.2021.4822

Corresponding Author: Sherrie Khadanga, MD, Division of Cardiology, Department of Medicine, University of Vermont, 62 Tilley Dr, South Burlington, VT 05403 (sherrie.khadanga@uvmhealth.org).

Author Contributions: Dr Khadanga and Mr Savage had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Khadanga, Savage, Rengo, Ades.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Khadanga, Savage.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Khadanga, Savage, Rengo.

Obtained funding: Khadanga.

Administrative, technical, or material support: Khadanga, Pecha, Rengo.

Supervision: Khadanga, Ades.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was supported by the National Institutes of Health Center of Biomedical Research Excellence award from the National Institute of General Medical Sciences (P20GM103644).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement 3.