Exercise Training in HFpEF: Functional Improvement Beyond Resting Diastolic Indices

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome in which exercise intolerance is one of the most prominent and disabling manifestations. Despite recent advances in pharmacological therapy, improving functional capacity and quality of life remains an important therapeutic goal. Exercise training is therefore an established component of heart failure management, with contemporary guidelines recommending regular exercise to improve exercise capacity and quality of life.¹⁾

In this issue of the International Journal of Heart Failure, the authors provide a systematic review and meta-analysis evaluating exercise training in selected East Asian patients with HFpEF.²⁾ The study is timely because much of the evidence supporting exercise training in HFpEF has been generated in Western populations. Previous meta-analyses have consistently demonstrated improvements in peak oxygen consumption (peak VO₂) and quality of life following exercise training.³,⁴⁾ However, evidence from East Asian populations remains comparatively limited.

The principal finding of the present study is clinically encouraging but imprecisely estimated; exercise training was associated with an approximately 2 mL/kg/min improvement in peak VO₂ compared with standard medical therapy. However, this pooled estimate was derived from only 4 studies involving 216 participants (105 exercise and 111 control), with one non-randomized study contributing approximately 46% of the overall weight. Consistent with these limitations, the certainty of evidence for peak VO₂ was rated as moderate and downgraded for inconsistency and imprecision. Conventional echocardiographic indices of diastolic function, including E/e′ and E/A, also did not significantly change; however, only 2 studies contributed to each diastolic endpoint, with substantial heterogeneity particularly for E/A. Thus, the findings support a potentially meaningful improvement in functional capacity, while the magnitude and robustness of this effect, as well as the effects on resting diastolic function, remain incompletely defined.

The apparent dissociation between improved peak VO₂ and unchanged resting diastolic indices is perhaps the most interesting aspect of this study. HFpEF was traditionally regarded primarily as a disorder of impaired left ventricular relaxation and increased chamber stiffness. This concept has evolved substantially, and HFpEF is now understood as a systemic syndrome in which cardiovascular abnormalities interact with multiple comorbidities and extracardiac mechanisms.⁵⁾

Exercise intolerance in HFpEF cannot be explained solely by resting left ventricular filling pressure. Impaired cardiac output reserve, chronotropic incompetence, pulmonary vascular dysfunction, endothelial dysfunction, abnormal skeletal muscle composition and metabolism, and impaired peripheral oxygen extraction can all contribute to reduced peak VO₂.⁶⁾ In particular, peripheral vascular and skeletal muscle abnormalities may have an important role in older patients with HFpEF, supporting the concept that exercise intolerance is ‘more than a heart problem.’⁷,⁸⁾

Exercise training may therefore improve functional capacity through mechanisms that are not adequately captured by resting E/e′ or E/A. Aerobic exercise can improve peripheral oxygen utilization and skeletal muscle function, and clinical trials have demonstrated meaningful increases in peak VO₂ even without major changes in resting cardiac structure or function.³,⁹⁾ Accordingly, the lack of significant change in E/e′ or E/A in the current meta-analysis should not be interpreted as evidence that exercise provides limited physiological benefit. The potential mechanisms underlying improved exercise capacity with exercise training in HFpEF are summarized in Figure 1.

Figure 1. Mechanisms underlying improved exercise capacity in HFpEF.

Exercise training may improve functional capacity through adaptations involving multiple organ systems, which may not be fully reflected by changes in resting diastolic indices. These complementary mechanisms may contribute to improved oxygen delivery and utilization during exercise.

HFpEF = heart failure with preserved ejection fraction; RV = right ventricle; VO₂ = oxygen consumption.

This observation also highlights the limitations of resting echocardiography as the sole measure of therapeutic response. HFpEF physiology frequently becomes most evident during exertion. Patients with apparently normal or mildly abnormal resting filling pressures may develop marked increases in pulmonary capillary wedge pressure during exercise.¹⁰⁾ Contemporary diagnostic approaches therefore incorporate exercise testing or exercise hemodynamics when resting evaluation is inconclusive.¹¹⁾

For studies examining exercise interventions, functional outcomes such as peak VO₂ and patient-reported functional status should consequently remain central endpoints. When feasible, cardiopulmonary exercise testing (CPET) combined with exercise echocardiography may provide complementary information regarding cardiac reserve, pulmonary pressures, chronotropic response, and the mechanisms responsible for exercise limitation.¹²⁾ Resting diastolic indices remain clinically useful, but they represent only one component of HFpEF physiology.

The focus on East Asian populations is another important contribution of the present analysis. HFpEF is particularly heterogeneous across geographic regions. Previous data from Asian patients with HFpEF have demonstrated considerable regional differences in comorbidity profiles, cardiac remodeling, and clinical outcomes.¹³⁾ These observations caution against assuming that findings derived predominantly from Western cohorts are necessarily applicable without qualification to all Asian patients.

At the same time, the current meta-analysis should not be regarded as definitive evidence for East Asia as a whole. The available studies were few and originated from only Japan, Taiwan, and China, while exercise modalities and study designs varied considerably. These limitations explain both the heterogeneity of the pooled estimates and the inability to determine whether one exercise modality is preferable to another. The study should therefore be viewed as an important synthesis of currently available regional evidence rather than a definitive description of exercise response across East Asian HFpEF.

What should clinicians take from these findings? First, the improvement in peak VO₂ supports exercise training as an important component of HFpEF management in appropriately selected East Asian patients, consistent with the broader international evidence.¹,³,⁴⁾ Second, therapeutic success should not be judged solely by changes in resting E/e′ or E/A. Improvement in exercise capacity may reflect adaptations across the cardiovascular system, peripheral vasculature, and skeletal muscle that are not apparent on resting echocardiography.

Future studies in Asian HFpEF populations should therefore prioritize adequately powered multicenter trials with standardized exercise protocols and clinically meaningful functional outcomes. Incorporating CPET and, where appropriate, exercise echocardiography may help clarify why individual patients improve and whether responses differ according to clinical phenotype. Given the marked heterogeneity of HFpEF, establishing reproducible regional evidence and identifying practical predictors of exercise response across different clinical phenotypes may represent a more relevant next step than pursuing highly complex precision strategies at this stage.¹⁴⁾

The current study reinforces a simple but important message: exercise capacity in HFpEF reflects more than resting diastolic function. Exercise training may improve functional performance without a detectable change in conventional diastolic indices. Recognizing this distinction may help us evaluate the benefits of exercise more appropriately and design future studies that better reflect the physiology and clinical experience of patients living with HFpEF.