This editorial refers to ‘Comparison of exercise training modalities and change in peak oxygen consumption in heart failure with preserved ejection fraction: a secondary analysis of the OptimEx-Clin trial’, by S. Mueller et al., https://doi.org/10.1093/eurjpc/zwae332.
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by symptoms such as shortness of breath, exercise intolerance and fatigue, and a left ventricular ejection fraction ≥50%. In addition, patients with HFpEF have a high hospitalization and mortality rate. It is expected that the prevalence of HFpEF will rise due to the aging population and its association with age-related comorbidities such as hypertension and diabetes.
Exercise training has consistently improved symptoms in patients with heart failure, which resulted in a Class 1A guideline recommendation for exercise.1,2 However, this recommendation does not distinguish between HFpEF or heart failure with a reduced ejection fraction. One of the most important benefits of exercise in patients with HFpEF is the improvement in exercise capacity, which is commonly measured by peak oxygen consumption (V̇O2). Peak V̇O2 and changes in peak V̇O2 after exercise-based interventions are important predictors for survival in this patient group.3
Some studies have suggested that the modality of exercise, such as high-intensity interval training (HIIT) or moderate continuous training (MCT), affects improvements in peak V̇O2 differently.4 However, the ‘Optimizing Exercise Training in Prevention and Treatment of Diastolic Heart Failure’ (OptimEx-Clin) trial, published in JAMA in 2021, included 180 patients with HFpEF and found no significant difference in the change of peak V̇O2 between HIIT and MCT after 3 and 12 months.5 Furthermore, neither exercise intervention groups reached the prespecified minimal clinically important difference in peak V̇O2 compared to the control group, which received one-time advice on physical activity according to the guidelines.
A potential explanation for the absence of a clinically important difference described by the authors was a substantial reduction in exercise adherence over time. Lower long-term adherence is a common and critical limitation of exercise interventions. Indeed, the per-protocol analyses of the OptimEx-Clin trial showed higher mean changes in peak V̇O2 compared with the complete case analysis. In addition, other studies confirmed that exercise characteristics might affect changes in peak V̇O2 in patients with heart failure.1–3
Within this issue of the European Journal of Preventive Cardiology, Mueller et al.6 performed secondary analyses on data from the OptimEx-Clin trial, examining the effect of exercise training characteristics on changes in peak V̇O2 in sedentary patients with HFpEF (mean age 69 years; 67% females) after 3 months of centre-based supervised exercise training. Within these secondary analyses, 46 patients were assigned to HIIT (3 × 38 min/week) and 45 to MCT (5 × 40 min/week). Exercise training characteristics consisted of exercise frequency, training duration, training intensity, and additional energy expenditure per week. A unique feature of these analyses is that exercise characteristics were objectively assessed with beat-by-beat heart rate data, which is more accurate than previously used exercise prescription variables.
The study showed that (i) the difference in the change in peak V̇O2 between HIIT and MCT was insignificant after adjustment for energy expenditure; (ii) higher training frequency and duration were associated with improved peak V̇O2 in both HIIT and MCT; (iii) higher exercise intensity, expressed as % heart rate reserve, did not improve peak V̇O2; and (iv) adding baseline O2 pulse further increased (up to one-third) the explained variability of the model for peak V̇O2 change when combined with exercise characteristics (10–20%). Therefore, the optimal exercise prescription to increase exercise capacity may be more focused on increasing training frequency and duration, and not necessarily on increasing exercise intensity. This provides more flexibility for health care professionals and patients to choose the modality and intensity of exercise that the patient prefers and the exercise that they can continue long term. This message aligns with the global health message ‘Every move counts towards better health’, where we would like to add that the best exercises are those that the patient keeps doing over time.
Although the results of the study are encouraging, some limitations need to be addressed. First, the study contains secondary analyses of a randomized controlled trial meaning that the study was not powered for these analyses. Therefore, the findings should be considered as exploratory and interpreted as observational associations instead of causal relationships. Future randomized controlled trials are necessary to confirm these results. Second, the analyses only included the change in peak V̇O2 at 3 months and not the outcomes at 12 months follow-up. This decision was made because it was likely that factors, such as adverse events, dropouts, variability in training frequency and intensity, changes in medical therapy, and larger intervals during cardiopulmonary exercise tests, reduce the statistical power. However, a follow-up of 3 months is relatively short and performing exercise for a longer period could impact the effects of exercise characteristics.
Nevertheless, the study of Mueller et al.6 can help refine exercise guidelines and recommendations in HFpEF patients. Future studies could examine the effects of exercise settings (centre-based vs. home-based vs. hybrid), modalities (aerobic only vs. combination with strength training), combinations with other lifestyle interventions (i.e. weight loss interventions7 or comprehensive cardiac rehabilitation), and, last but not least, strategies to improve the currently low uptake of exercise-based interventions in heart failure8 and long-term adherence to exercise or physical activity interventions.1,2
New strategies to improve exercise adherence contain e.g. (i) intermittent, in-person exercise training sessions to increase and maintain the exercise dose, (ii) risk stratification for patients with high and low adherence, and (iii) behavioural economics including insurance incentives, commitment contracts, and social networks. These strategies are emerging and innovative paradigms for a sustainable physically active lifestyle in patients with heart failure.9 Finally, digital technologies including smartphones or consumer wearables will be important assets to improve and encourage a physically activity lifestyle by providing direct feedback during exercise (e.g. heart rate) and feedback over time with longitudinal physical activity monitoring. In the future, digital technologies could overcome several challenges related to cardiac rehabilitation in patients with HFpEF. For example, digital tools could increase the access to and uptake of cardiac rehabilitation as it provides opportunities for remote monitoring and potentially removes the necessity for in-person sessions at the cardiac rehabilitation centre. In addition, remote monitoring with digital tools provides the flexibility to fit exercise into the patients’ daily schedule and the possibility to exercise more often and longer that is not bound by the number and duration of exercise sessions that is provided at the cardiac rehabilitation centre. Nevertheless, several gaps related to for example implementation and digital health equity need to be addressed to ensure that all HFpEF patients could benefit from exercise-based cardiac rehabilitation.10
In summary, the secondary analysis of the OptimEx-Clin trial published in this issue of the European Journal of Preventive Cardiology is an important attempt to improve the effectiveness of exercise training and provide guidance on exercise and physical activity prescriptions in a growing population of patients with HFpEF. Furthermore, the paper of Mueller et al. highlights relevant exploratory results with important leads for future studies.
Contributor Information
Esmée A Bakker, Department of Physical Education and Sports, Sport and Health University Research Institute (iMUDS), University of Granada, Carretera de Alfacar, S/N, 15 C.P.18071, Granada, Spain; Department of Primary and Community Care, Radboud university medical center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Seth S Martin, Digital Health Innovation Laboratory, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Funding
E.A.B. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 101064851. Outside of the present work, S.S.M. reports research support from the American Heart Association Health Technologies and Innovation Strategically Focused Research Network (20SFRN35380046, 20SFRN35490003), a collaborative project of this network (#878924), and additional American Heart Association support (#882415, #946222). He also reports support from the Patient-Centered Outcomes Research Institute (ME-2019C1-15 328, IHS-2021C3-24147), the National Institutes of Health (NIH) (P01 HL108800, R01AG071032), the David and June Trone Family Foundation, the Pollin Digital Innovation Fund, Sandra and Larry Small, Google, and Merck.
Data availability
No new data were generated or analysed in support of this research.
References
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Data Availability Statement
No new data were generated or analysed in support of this research.