Acute decompensated heart failure (ADHF) usually occurs in patients with a history of heart failure (HF) and reduced left ventricular ejection fraction (LVEF). It is the main cause of unplanned hospitalizations and is associated with poor health-related quality of life, higher mortality, and an increased rate of rehospitalization [1]. Mortality or rehospitalization rates after one year following hospital discharge are increased from 25% to more than 45% [1]. The majority of patients with ADHF are elderly and frail, with severe impairments in strength, balance, mobility, and endurance [2]. The presence of these physical disabilities may explain the high rate of rehospitalization with ADHF, since most ADHF patients were rehospitalized not for recurrence of heart failure, but due to the comorbidities and complications resulting from these physical impairments [3].

Cardiac rehabilitation (CR) involves a comprehensive program in those patients with heart failure and a reduced ejection fraction (HFrEF; left ventricular ejection fraction [LVEF 40%]) [4]. Exercise-based rehabilitation is an important part of the treatment regimen and is a grade I A recommendation by the ESC clinical guidelines for chronic heart failure, which has been shown to improve exercise capacity, and quality of life, and reduce hospitalization for heart failure [1]. Current clinical management strategies for ADHF do not include patients with physical impairments, and these patients are usually excluded from in-patient cardiac rehabilitation programs. Recently, some studies had explored the efficacy and safety of transitional, individualized, and progressive early cardiac rehabilitation programs initiated during, or early after, hospitalization in ADHF patients [5, 6, 7, 8].

The present meta-analysis reviewed recent randomized controlled trials (RCTs) in which early exercise-based rehabilitation in patients with acute decompensated heart failure began during, or early after, hospitalization and compared the efficacy and safety of cardiac rehabilitation with patients who didn’t receive cardiac rehabilitation.

Six studies were included in this meta-analysis. All 6 studies used random grouping to divide the patients into early exercise-based rehabilitation groups, and controls or usual care groups which did not receive any exercise training by clinicians. Among these studies, there were some differences in rehabilitation protocols, duration of rehabilitation, and assessment of the quality of life. However, to our knowledge, the present study is the first meta-analysis evaluating early exercise-based rehabilitation for hospitalized patients with ADHF, including those beginning rehabilitation shortly after hospitalization. Our findings demonstrated that early exercise-based rehabilitation was safe and significantly improved physical function as assessed by 6MWD and the short physical performance battery (SPPB) in the patients with ADHF.

Physical disabilities, frailty, and depression are often clinically unrecognized in older patients hospitalized for acute heart failure and are generally not addressed in clinical care pathways, and may contribute to delayed, incomplete recovery and higher rates of rehospitalization, death, and long-term loss of independence after hospital discharge. Patients with acute heart failure, including those who were able to walk independently before hospitalization, spend most of their time in bed during hospitalization [15]. Long-term bed rest worsens physical function and increases the risk of cognitive decline and psychological disorders [16]. The cause of inactivity during hospitalization is multi-factorial. Cardiologists are usually concerned about the safety of moving patients out of bed too early in order to prevent falls, as well as the traditional concept that patients should stay in bed when they have a serious illness [17]. Studies have shown that the mean baseline 6-minute walk distance is less in acute decompensated heart failure compared to chronic heart failure. In addition, severe leg weakness does not allow standing from a seated position without the use of the patient’s arms [18].

Cardiac rehabilitation is an important part of the comprehensive therapeutic regimen for chronic heart failure (HFrEF) and has been shown to significantly improve physical function, exercise capacity, quality of life, and reduces hospitalizations [19, 20, 21]. Currently, exercised-based rehabilitation for heart failure is usually initiated in the period after hospital discharge when physical dysfunction is improved. Previous studies of rehabilitation commonly exclude those patients who had been hospitalized within six weeks from discharge [18, 22]. The evidence for beginning rehabilitation during this period was unclear. Kitzman et al. [5] demonstrated that patients with ADHF who undertook early exercise-based training significantly improved the short physical performance battery (SPPB) and 6MWD, and that the procedure was relatively safe. SPPB is a comprehensive measure in elderly patients to evaluate muscle function and strength [23]. Previous studies had shown that poor SPPB is closely associated with frailty in elderly hospitalized patients with cardiovascular disease, and is an independent risk factor for frailty, which can accurately predict patient disability, rehospitalization, home treatment, and death [24, 25]. Our pooled analysis of included studies also demonstrates that patients who undertake early exercise-based rehabilitation have significant improvement in physical function compared with those patients who undertake usual care without any other rehabilitation training. Quality of life assessments including the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Short Form-36 Health Survey (SF-36) [26], and the Barthel Index (BI) [27] also improved in our meta-analysis and was consistence with improvement in physical function.

Rehabilitation programs should be individualized for every patient based on basic performance level. Most ADHF patients will begin at a low level, since they present frailty and a lower level of physical function. Kitzman et al. [5] reported that the exercise protocol should be analyzed by multiple domains including endurance, strength, balance, and flexibility. The initiation of rehabilitation for most patients was usually in the low level after individualized assessment of these domains. For example, intensity was determined by the patient’s rate of perceived exertion (RPE) and the target for inpatients was RPE $\le$12 [5]. Balance and flexibility are usually in the lower level at baseline and the deficits in balance, flexibility, and mobility are more likely to lead to falls and injuries following the initiation of strength and endurance training, however, it is less common in chronic heart failure. Thus, training for balance and flexibility should be strengthened [5]. In Hui Zhong’s rehabilitation protocol, the patients with cardiac function IV in the four-step protocol received exercise training in bed, including breathing exercises and ankle foot movements, rather than out of bed [13].

Although the duration of these early rehabilitation protocols differed, four out of six included studies reported early rehabilitation during hospitalization combined with clinic rehabilitation. Cardiac rehabilitation during, or early after, hospitalization combined with rehabilitation for a period after hospital discharge mirrors the pathophysiological process of heart failure from the time of acute decompensation, through the transition to recovery, and finally to the return to a chronic, stable stage. Thus, this rehabilitation process from hospitalization to the clinic for acute decompensated heart failure should be more utilized in clinical practice.

However, it should be noted that not all in-patients with ADHF are suitable for early exercise-based rehabilitation, especially those in-patients with severe lower limb weakness and balance problems [28]. If a patient falls and is injured, the patient’s willingness to participate in cardiac rehabilitation is decreased. The rate of falls or injuries, and chest pain during exercise training were not significantly different in the included studies in this meta-analysis, which may have been due to the improved exercise capacity of these patients at baseline and the tailored rehabilitation protocol that was instituted. The patients who undertake the REHAB-HF protocol can walk at least 4 m at enrollment and an individualized rehabilitation protocol is based on an assessment of physical function in the four-domains at baseline. These inclusion criteria are the foundation for a successful exercise training program in ADHF patients. Furthermore, the exercise rehabilitation programs should be supervised by a rehabilitation clinician in a monitored environment to ensure that the process of supervised rehabilitation is relatively safe.

The clinical evidence that early transitional rehabilitation during hospitalization for patients with ADHF is safe and effective remains limited and more data is need to determine its long-term benefits. Early transitional rehabilitation for ADHF still faces great challenges, and requires the cooperation of patients, nurses, and physicians. However, our findings lend further support for the concept that rehabilitation should begin in the hospital. Our meta-analysis suggests that early exercise-based rehabilitation is an important treatment for ADHF. Proper selection of patients, supervised rehabilitation protocols, and individualized patient assessment are the key elements for a successful program. A transitional, individualized, progressive exercise-based rehabilitation program initiated during hospitalization combined with home-based or clinic rehabilitation is an integrated rehabilitation strategy for acute decompensated heart failure.

The limitations of this study should be acknowledged. First, the number of included studies and sample size of the analysis are small, which reflects the limited number of studies on early rehabilitation in ADHF. However, this increases the risk of selection bias. Second, studies with device-assisted rehabilitation methods were excluded, such as electrical muscle stimulation and non-invasive ventilation. Third, the duration of rehabilitation included in this study varied from at least ten days to three months, which also increases the risk of bias. Fourth, the rehabilitation protocols varied amongst the studies. Finally, although blinding was used in the included studies, and the staff members who assessed the primary outcome were unaware of the trial group assignments, it was not possible for patients to be unaware of the group to which they had been randomly assigned; which also increased the risk of bias.

This meta-analysis demonstrated that early exercise-based rehabilitation for eligible in-patients with ADHF starting during, or early after, hospitalization, is relatively safe and could improve physical function. For patients with acute decompensated heart failure, a transitional, individualized, progressive exercise-based rehabilitation program during hospitalization combined with home-based or clinic rehabilitation is an integrated rehabilitation strategy.

ADHF, Acute Decompensated Heart Failure; CR, Cardiac Rehabilitation; SPPB, Short Physical Performance Battery; EF, Ejection Fraction; LVEF, Left Ventricular Ejection Fraction; 6MWD, 6-Minute Walk Distance; RPE, Rate of perceived exertion.

DYH, ZYJ and JC designed the research study. LSL, XXP, NZ, MMZ, LHZ, XXR, TZ, PCZ, ZYJ, JC performed the research and analyzed the data. JC, LSL, ZYJ drafted the manuscript. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript.

Since this is a review article, this article does not contain any studies with human participants or animals performed by any of the author.

Not applicable.

This work was supported by grant No.2022-3-7088 from the Capital’s Funds for Health Improvement and Research (CFH) to Dr. Lisong Liu.

The authors declare no conflict of interest.