The 30th Japanese Association of Cardiac Rehabilitation Annual Meeting (2024)
Cardiac Rehabilitation and Heart Failure With Preserved Ejection Fraction
2025 年 7 巻 10 号 p. 837-841
詳細
2025 年 7 巻 10 号 p. 837-841
Heart failure with preserved ejection fraction (HFpEF) is becoming increasingly prevalent in aging societies. A recent multicenter cohort study in Japan demonstrated that cardiac rehabilitation (CR) significantly improves the prognosis of patients with HFpEF and frailty. The 2025 Japanese Heart Failure Guidelines recommend pharmacologic therapies for HFpEF. Recent international trials have led to the adoption of sodium-glucose transporter 2 inhibitors and angiotensin-receptor-neprilysin inhibitors in Japan, supported by evidence showing reduced rates of heart failure readmission. However, it should be noted that the majority of patients enrolled in those trials were in their early 70s. In real-world clinical practice, the number of patients in their 80s and 90s receiving treatment is increasing. This older population is more susceptible to adverse effects such as orthostatic hypotension, hyperkalemia, and urinary tract infections. Polypharmacy further complicates medication management. In such cases, CR plays a vital role in maintaining quality of life and supporting long-term prognosis. Furthermore, HFpEF is frequently accompanied by comorbidities such as atrial fibrillation, hypertension, and ischemic heart disease. It is important to note that elderly patients are also susceptible to additional conditions, including cerebrovascular disease, musculoskeletal disorders and malignancies. A multidisciplinary approach to CR, tailored to these complex health profiles, is essential to prevent the progression of functional decline and frailty.
Comprehensive cardiac rehabilitation (CR) is a critical part of daily clinical practice because, beyond exercise training, CR encompasses nutrition and dietary counseling, patient education, disease management, and psychological support.1,2 All of these components are essential for optimizing patient outcomes, particularly in the growing population of older adults with cardiovascular disease (CVD).3
In this context, maintaining basic physical function, especially lower-limb muscle strength and walking ability, has become a central goal of CR. Conditions such as sarcopenia and frailty are now recognized as important considerations in the care of older adult cardiac patients.4 Moreover, with the increasing prevalence of heart failure (HF), CR has expanded its focus to include patients with HF with preserved ejection fraction (HFpEF).5 Special attention is given to rehabilitation following transcatheter aortic valve implantation, cardiac device implantation, endovascular treatment for aortic disease, and in cases of pulmonary hypertension (PH).
Older patients, particularly the super-aged, constitute a key demographic among HFpEF populations and are expected to further increase in number.6 Additionally, in this review we highlight the emerging field of onco-cardiology, where the role of CR is gaining attention due to the cardiovascular (CV) complications of cancer therapies.
Looking ahead, we discuss future directions for CR, including its theoretically ideal application in the recovery phase and the integration of CR with home medical care, community-based comprehensive care, and palliative care services. Finally, we introduce the use of telemedicine as a novel and promising strategy for enhancing outpatient and maintenance CR.
HF is the most rapidly growing global burden among CVD and is associated with a high risk of recurrent CV events. Comorbidities are highly prevalent in HF patients and significantly contribute to adverse clinical outcomes.7–11
HF is classified into 3 subtypes based on left ventricular ejection fraction (LVEF): HF with reduced EF (HFrEF), mildly reduced EF (HFmrEF), and preserved EF (HFpEF). HFmrEF may evolve toward either HFrEF or HFpEF; however, its phenotype typically resembles that of HFrEF, often with underlying coronary artery disease (CAD). HFrEF and HFpEF differ markedly in their pathogenesis and disease progression, driven by distinct molecular and cellular mechanisms.12
In HFpEF, extracardiac comorbidities (e.g., metabolic syndrome, hypertension, and renal dysfunction) promote left ventricular remodeling via systemic inflammation and coronary microvascular endothelial dysfunction. These changes contribute to diastolic dysfunction through macrophage infiltration and interstitial fibrosis, along with altered paracrine signaling that induces cardiomyocyte hypertrophy and stiffness due to impaired nitric oxide-cyclic guanosine monophosphate signaling. Systemic inflammation also affects the lungs, skeletal muscles, and kidneys, contributing to PH, muscle weakness, and fluid retention.13
Targeted interventions address specific pathophysiologic pathways: caloric restriction (metabolic risk), statins (inflammation), phosphodiesterase-5 inhibitors (PH), exercise (muscle weakness), diuretics and monitoring devices (sodium retention), nitrate-nitrite therapies (NO bioavailability), neprilysin or PDE9 inhibitors (cGMP restoration), and spironolactone (fibrosis). Given the phenotypic diversity of HFpEF, personalized therapeutic approaches are advocated and mapped in a matrix format that correlated the HFpEF presentation with individual predispositions.
PH and right ventricular dysfunction have emerged as key features in HFpEF;13–16 they are conditions that share clinical outcomes with HFrEF but differ in etiology,17 cardiac remodeling, comorbidities, and treatment response.18
Pharmacologic Therapy for HFpEFEarly randomized trials of pharmacologic therapy for HFpEF aimed to export the success of treatment with neurohormonal antagonists including angiotensin-converting enzyme inhibitors (PEP-CHF [Perindopril in Elderly People with Chronic Heart Failure trial]),19 angiotensin-receptor blockers (CHARM-Preserved [Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity-Preserved],20 I-Preserve [Irbesartan in Heart Failure With Preserved Systolic Function]),21 and MRAs (TOPCAT [Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist])22 from patients with HFrEF to those with higher EFs, but were generally unsuccessful.23 Accordingly, instead of targeted pharmacologic therapy, HF treatment guidelines have historically emphasized decongestion for relief of symptoms and aggressive management of comorbidities such as hypertension, diabetes, CAD, and atrial fibrillation (AF). However, with the publication of data from more recent randomized trials of angiotensin-receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), specific pharmacologic interventions are now appropriate to consider for many patients with HFpEF.24–27
Although patients with HFpEF comprise nearly half of those with chronic HF, evidence-based treatment options for this population have historically been limited. Recently, however, emerging data from prospective, randomized trials enrolling patients with HFpEF have significantly altered the range of pharmacologic options to modify disease progression in selected patients with HFpEF.
Medications for comorbidity management are prescribed by current guidelines, often leading to an increase in the number of medications consumed. Polypharmacy has become increasingly relevant for patients with HF, due to the expanding armamentarium of guideline-directed medical therapies for treating HF.28–30 Polypharmacy is the common use of ≥5 medications daily; however, taking ≥10 medications is notable, representing a condition described as hyperpolypharmacy in the geriatric and pharmacology literature.31,32 Polypharmacy is reported to be associated with adverse clinical outcomes in older adults.33,34 The clinical relevance of hyperpolypharmacy has been proposed, but data on its prognostic effect on deaths in HF remain limited. Furthermore, there is a paucity of data on the associations between the number of medications stratified by medication class (CV medications vs. non-CV medications) and adverse events.
CR for HFpEFClinical Significance HFpEF is a heterogeneous syndrome increasingly affecting older adults. Pharmacologic treatments have shown limited benefit, but recent evidence underscores the effectiveness of CR as a multidimensional intervention with significant clinical implications (Table).
Clinical Significance and Mechanisms of CR in HFpEF
| Clinical significance of CR |
Mechanisms of improvement |
|---|---|
| Exercise capacity | Improved endothelial function |
| Quality of life | Reduced catecholamine spillover |
| Functional status | Increased peripheral oxygen extraction |
| Symptom reduction | Enhanced peak oxygen consumption |
CR, cardiac rehabilitation; HFpEF, heart failure with preserved ejection fraction.
Exercise Capacity CR enhances exercise tolerance and peak oxygen consumption (peak V˙O2) in HFpEF patients.35 These improvements are comparable to or exceed those seen in HFrEF patients and are attributed to CR’s pleiotropic effects, targeting both the central and peripheral mechanisms underlying exercise intolerance.
Quality of Life and Functional Status CR contributes to improved health-related quality of life (HRQoL) by addressing physical, psychosocial, and behavioral dimensions.36,37 Functional improvements in HFpEF include increased lower-limb muscle strength, better gait speed, and enhanced ability to perform activities of daily living, which are prognostic for better outcomes.
Symptom Relief CR alleviates common HFpEF symptoms such as exertional dyspnea and fatigue, offering symptom palliation and improved patient comfort, especially important in older adults with multiple comorbidities.38
Individualized Approaches for HFpEF Phenotypes CR may positively affect clinical outcomes such as emergency visits, hospital readmissions, and deaths. However, evidence from large-scale HFpEF-specific randomized controlled trials is still limited, necessitating further research stratified by phenotype.
Given the heterogeneity in HFpEF, including phenotypes with obesity, AF, and chronic kidney disease, tailored CR programs are essential. These may include moderate-intensity continuous training,39 high-intensity interval training,40 resistance training, and balance exercises adapted to the patient’s profile.
Sedentary Lifestyle Sedentary behavior independently contributes to CV risk and functional decline. Japan’s National Plan for CVD Control emphasizes addressing this issue. Integrating sedentary time reduction into CR programs may enhance outcomes. Understanding the interplay between physical activity and sedentary time is a key area for future investigation.41
Comprehensive RoleAs illustrated in the Figure, CR is expected to confer multifaceted benefits for patients with HFpEF, targeting not only central cardiac function but also peripheral organ systems such as skeletal muscle, kidney, and brain, which are frequently compromised in this population. Integration of aerobic and resistance training may attenuate myocardial remodeling, improve mitochondrial bioenergetics, and alleviate systemic complications.
Conceptual model of cardiac rehabilitation (CR) in heart failure with preserved ejection fraction (HFpEF). CR, including aerobic walking and resistance training, is hypothesized to improve exercise tolerance and systemic organ function in patients with HFpEF, which is associated with cardiomyocyte hypertrophy, interstitial fibrosis, and mitochondrial dysfunction, as well as functional impairments of other organs such as the kidneys, brain, and skeletal muscle. CR may help counteract these multi-organ pathophysiological changes.
Multidisciplinary and Holistic Approach Given the limited efficacy of pharmacologic therapies for HFpEF, CR emerges as a clinically meaningful intervention. The World Health Organization defines CR as a multifactorial intervention aiming to improve HRQoL through physical, psychological, social, and occupational support. Accordingly, modern CR programs should extend beyond exercise training to encompass nutrition and diet therapy, patient education, disease management, and psychological counseling. Notably, the increase in exercise capacity observed in HFpEF patients through CR is comparable to, or even exceeds, that seen in patients with HFrEF.42 This holistic approach facilitates functional recovery and reintegration into daily life.43
CR is inherently multidisciplinary, requiring collaboration among cardiologists, rehabilitation physicians, nurses, physiotherapists, dietitians, and psychologists.44 Such teams are essential in tailoring interventions to individual needs, particularly in older and more complex patient populations.
Physical Function and Aging Population With the growing prevalence of older adults with CVD, CR must prioritize the restoration and maintenance of basic physical functions. Lower-limb muscle strength and walking ability are fundamental targets, given their close association with exercise capacity, frailty, and independence. Interventions aimed at preventing or reversing sarcopenia and frailty are particularly vital in HFpEF, where these conditions often coexist and worsen clinical outcomes.
Special Considerations for Older Patients Older HFpEF patients, including the super-aged, represent a particularly vulnerable subgroup requiring individualized CR strategies.45 Programs should be adapted for those receiving advanced therapies such as inotropes, ventricular assist devices (including implantable types), or heart transplantation. Additionally, the growing relevance of onco-cardiology necessitates incorporating cancer-related CV care into CR frameworks, especially as cancer survivors with CV comorbidities increasingly enter the HFpEF population.
Telemedicine and New Models of CR In the post-COVID-19 era, telemedicine enables the expansion of CR access.46 Virtual CR incorporating wearable devices can remotely monitor blood pressure, heart rate, oxygen saturation, and physical activity. Tele-CR programs may be especially beneficial for frail or remote-living patients, although further evidence is needed to validate their safety and efficacy.
Study LimitationsThis is a narrative review reflecting the authors’ perspectives and recent literature, focusing mainly on CR in Japan and select international contexts. It is not a systematic review, and it does not encompass all potential modifiers of CR effectiveness.
CR is a cornerstone in the non-pharmacologic management of HFpEF. It provides substantial improvements in exercise capacity, QoL, functional status, and symptom relief. Individualized CR programs that incorporate phenotype-specific interventions and reduce sedentary behavior may further enhance patient outcomes. Future randomized control trials should evaluate long-term clinical endpoints and the cost-effectiveness of CR in this growing patient population.
The authors thank all those who contributed to this review. This paper summarizes the results presented at the 30th Annual Meeting of the Japanese Association of Cardiac Rehabiltation and its Joint Symposium in Kobe, Japan, in 2024. We express our sincere gratitude to all those involved.
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A.H. and A.S. supervised and prepared the text. Both authors reviewed the text and agreed with the paper’s publication.
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