Ambulatory Programs in Acute Heart Failure Care: Enhancing Patient Prognosis

1. Introduction

The global prevalence of heart failure (HF) is escalating in tandem with aging populations [1]. Despite advancements in medical therapies, readmission rates for HF remain stubbornly high, posing a significant challenge to healthcare systems [2]. While guideline-directed medical therapy has effectively reduced cardiac deaths, the frequency of HF-related rehospitalizations has not seen a corresponding decline [3]. Conversely, exercise therapy is increasingly recognized for its therapeutic benefits across a spectrum of conditions, including mental health disorders and infectious diseases [4,5].

A growing body of evidence underscores the efficacy of comprehensive cardiac rehabilitation for HF patients. These programs are shown to improve exercise tolerance, decrease hospital readmissions [6,7], and enhance long-term prognosis. These benefits are attributed to several mechanisms, including the modulation of neurohumoral factors and inflammatory cytokines [8,9], and the improvement of skeletal muscle metabolic dysfunction [10]. Recent studies highlight that comprehensive cardiac rehabilitation, incorporating exercise training, is effective in reducing HF readmission rates, irrespective of left ventricular ejection fraction (LVEF) [7].

In Japan, cardiac rehabilitation is guided by the “Standard Cardiac Rehabilitation Program for Heart Failure,” endorsed by the Japanese Society of Cardiac Rehabilitation [11]. This program advocates for the initiation of the acute-phase ambulation program (AAP) at the patient’s bedside immediately following hemodynamic stabilization. This early intervention aims to facilitate the timely commencement of exercise training. The AAP involves a graded loading test in the acute phase, where bed rest levels are progressively reduced as vital signs remain stable. Starting with minimal exercise intensity, such as sitting, the program gradually escalates the exercise load and further reduces bed rest. For patients with severe HF, frailty, or those requiring circulatory support who struggle with even low-intensity exercise, alternative strategies such as low-intensity resistance training, bed-based rehabilitation, and neuromuscular electrical stimulation are employed to mitigate disuse-related decline [11].

Despite the established framework for AAP, its effectiveness remains under-evaluated. We hypothesized that AAP could lead to improved cardiovascular outcomes post-discharge in HF patients. Therefore, this study aimed to investigate the association between initiating AAP and the prognosis of patients experiencing worsening HF, specifically focusing on the relationship between AAP implementation and cardiovascular events after hospital discharge.

2. Methods

2.1. Patient Population

This retrospective, single-center study was conducted at Fujita Health University Hospital in Toyoake City, Japan, a specialized medical facility. We reviewed the records of consecutive patients admitted for worsening HF between March 2019 and April 2021. The Institutional Review Board of Fujita Health University approved the study protocol (identifier: HM20-161), and waived the need for written informed consent due to the retrospective nature of the study.

Our hospital implemented AAP for all patients admitted with worsening HF starting in May 2020. The study cohort comprised 560 patients admitted between May 2019 and April 2021. Patients who received AAP, admitted between May 2020 and April 2021, constituted the AAP group (n = 284). Patients admitted before AAP implementation, between May 2019 and April 2020, formed the conventional care group (n = 276). Patients who died during hospitalization or could not be followed for 180 days post-discharge were excluded. The final analysis included 247 patients in the AAP group and 232 in the conventional group (Figure 1).

Figure 1. Study Flow Diagram

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2.2. Outcome Measures and Data Collection

The primary outcomes assessed were all-cause mortality and readmission for worsening HF within 180 days post-discharge. Data on cardiovascular events were collected from outpatient medical records.

Patient data was extracted from medical records, including demographics such as age, sex, body mass index (BMI), etiology of HF, medications, and comorbidities. Echocardiography and blood samples were obtained upon admission. Left ventricular ejection fraction (LVEF) was measured using the modified Simpson’s rule. Serum levels of total protein, hemoglobin, and N-terminal pro-brain natriuretic peptide (NT-proBNP) were also recorded.

2.3. Statistical Analysis

Continuous variables were compared using the unpaired Student’s t-test or Mann–Whitney U test, and presented as mean ± standard deviation (SD) or median (interquartile range (IQR)) as appropriate. Categorical variables, expressed as numbers or percentages, were analyzed using the chi-squared test. Predictive capabilities were assessed using univariate and multivariate Cox regression analyses. The Cox regression model incorporated potential prognostic and confounding factors, including log NT-proBNP, hemoglobin, BMI, LVEF, chronic kidney disease (CKD), and history of HF hospitalization as adjusting variables. Kaplan–Meier analysis with a log-rank test was used to compare HF readmission rates between the AAP and conventional groups. Statistical analyses were performed using JMP Pro ver. 15.1.0, with statistical significance set at p < 0.05.

3. Results

3.1. Patient Demographics and Clinical Events

Baseline characteristics of the patient groups are detailed in Table 1. The AAP group exhibited a statistically significant higher BMI and heart rate compared to the conventional group. However, mean age, sex distribution, and medical history were comparable between the two groups. Prescription rates for sodium–glucose transporter 2 (SGLT2) inhibitors and angiotensin receptor–neprilysin inhibitors (ARNIs) were significantly greater in the AAP group. Hemoglobin and total protein levels showed no significant differences between the groups. Intravenous diuretic use during hospitalization was similar (conventional group: 94% vs. AAP group: 92%), as was dobutamine administration (conventional group: 22% vs. AAP group: 26%). Post-discharge medications remained consistent with discharge prescriptions for all patients. Notably, the conventional group had a significantly higher rate of prior hospitalization for HF compared to the AAP group.

Table 1. Patient Characteristics at Baseline

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*p value < 0.05 is statistically significant.

3.2. Survival Analysis

Kaplan–Meier survival curves demonstrated a significantly lower rate of cardiac events in the AAP group compared to the conventional group (Figure 2). This difference was statistically significant for both HF readmission and the composite primary endpoint (p = 0.020 and p = 0.014, respectively).

Figure 2. Kaplan-Meier Curves for Cardiac Events

Kaplan-Meier curves comparing time to cardiac event between acute-phase ambulation program and conventional care groups for heart failure patients. (A) Primary composite endpoint. (B) Rehospitalization due to HF.

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Analyzing readmission as a singular event, the AAP group exhibited a significantly higher event avoidance rate compared to the conventional group.

3.3. Regression Analysis

Table 2 presents the results of univariate and multivariate Cox regression analyses for the primary endpoint. Univariate analysis identified AAP participation as a significantly protective factor against primary events. Multivariate analysis, adjusting for age, sex, history of HF, systolic blood pressure, use of renin–angiotensin system inhibitors or angiotensin receptor blockers, hemoglobin, NT-proBNP, and AAP participation, confirmed AAP participation as an independent factor significantly associated with a reduced risk of primary endpoint occurrence (hazard ratio 0.62, 95% confidence interval 0.41–0.95, p = 0.028).

Table 2. Cox Regression Hazard Models for Rehospitalization and All-Cause Death

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*p value < 0.05 is statistically significant.

4. Discussion

This retrospective study examined the association between initiating AAP and the occurrence of all-cause mortality and readmission for worsening HF within 180 days post-discharge in 479 patients hospitalized for acute HF. Our findings suggest that the implementation of AAP in our hospital was associated with a reduction in cardiovascular events compared to the period before its implementation.

Mobility protocols, such as AAP, that incorporate structured exercise training have been shown to reduce hospital stays [12] and improve patients’ ability to perform activities of daily living (ADLs) at discharge [13] in non-cardiac ICU settings. However, evidence linking mobility protocols during hospitalization for HF and post-discharge prognosis has been limited. A prior study suggested that mobility protocols in hospitalized HF patients improved HF readmission rates, but it had a short follow-up and lacked multivariate analysis [14]. Our study is among the first to demonstrate a significant association between initiating AAP during hospitalization and improved post-discharge prognosis in HF patients.

One potential mechanism for improved prognosis following AAP initiation is the maintenance of muscle strength. Reduced muscle strength elevates ergoreceptor activity, impacting sympathetic and neurohumoral systems, contributing to dyspnea and HF exacerbation. This cascade can also trigger endocrine imbalances, peripheral circulatory insufficiency, inflammation, and oxidative stress, creating a detrimental cycle that further diminishes muscle strength [9]. Chronic HF can lead to a shift in muscle fiber types, decreasing type I fibers and increasing type IIb fibers, promoting anaerobic metabolism and lactic acidosis, potentially exacerbating HF [10]. Studies in ICU patients without HF have shown that early aerobic exercise training can preserve muscle strength [15]. Furthermore, research by Hülsmann et al. indicated that greater knee flexor strength is associated with improved 5-year survival in patients with reduced ejection fraction HF [16]. These findings support our study’s results, suggesting early mobilization through AAP helps maintain muscle strength during hospitalization, positively influencing post-discharge outcomes.

Another contributing factor could be AAP’s role in prompting exercise prescription at discharge. AAP implementation may encourage physicians to recommend and prescribe exercise regimens for patients post-hospitalization. Kamiya et al.’s multicenter study demonstrated that regular exercise training (three to five times weekly within 3 months post-discharge) reduced cardiovascular events in HF patients, regardless of EF [7]. Thus, AAP may improve adherence to post-discharge exercise recommendations, contributing to better outcomes for HF patients.

Finally, AAP during hospitalization may facilitate patient education on HF self-management by a multidisciplinary team. These programs provide an opportunity for comprehensive education on self-management strategies. Jonkman et al. reported that multidisciplinary team-based self-management interventions, in conjunction with exercise training, decreased HF-related readmission and all-cause mortality within 6 months of discharge [17]. While not all patients in our study completed the entire AAP progression, its implementation likely improved prognosis through mechanisms beyond muscle strength maintenance, potentially including enhanced patient self-management skills and multidisciplinary care coordination.

Study Limitations

Several limitations should be considered when interpreting our findings. First, the patients in this study may not have received optimal contemporary medical therapy. The prescription rates of ARNIs and SGLT2 inhibitors were low, as these medications were relatively recent additions to HF treatment guidelines in Japan during the study period. Furthermore, the prescription rates of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists were also lower than current guidelines might recommend, potentially due to the inclusion of a large number of elderly patients with comorbidities like hypotension and renal failure [18], reflecting the aging demographic in Japan. These factors may limit the generalizability of our findings to contemporary HF populations in other countries with different prescribing patterns. Although SGLT2 inhibitor and ARNI use was more frequent in the AAP group, these medications were not found to be significant predictors of event occurrence in Cox regression analysis within our study.

Second, we lacked data on muscle mass, the duration of HF education provided, and the specifics of post-discharge exercise training. Third, cardiopulmonary exercise testing was not consistently performed pre- and post-hospitalization. VO2 max from cardiopulmonary exercise testing is a valuable prognostic indicator in HF [19], and future prospective studies could incorporate VO2 max as a key outcome measure. Finally, the study’s single-center, retrospective design introduces the potential for unmeasured confounding variables.

5. Conclusions

This study demonstrates a significant association between the initiation of AAP and reduced all-cause mortality and readmission rates in patients hospitalized for HF. These findings suggest that implementing mobility protocols in the acute phase of HF may be beneficial in improving short-term prognosis. Incorporating ambulatory programs into acute heart failure care should be considered as a strategy to enhance patient outcomes.

Author Contributions

Conceptualization, H.I.; methodology, H.I.; formal analysis, Y.F. and H.T.; data curation, Y.F., Y.K., H.K., M.H. (Meiko Hoshino), A.Y., T.M., M.H. (Masahide Harada), Y.O. and M.Y.; writing—original draft preparation, Y.F.; writing—review and editing, H.I., M.Y. and H.K. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the institutional review board of Fujita Health University (identifier: HM20-161).

Informed Consent Statement

The requirement for obtaining written informed consent was waived because of the retrospective study design.

Data Availability Statement

Data are stored in the hospital’s secure database.

Conflicts of Interest

Hideo Izawa has received grant support through his institution from Bayer, Daiichi Sankyo, Sumitomo Dainippon, Kowa, Ono, Otsuka, Takeda, and Fujifilm Toyama Kagaku and honoraria for lectures from Otsuka, Novartis, and Daiichi Sankyo.

Funding Statement

This research was supported by JSPS KAKENHI (Grant No. 19K08567) (H.I.).

Footnotes

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Associated Data

Data Availability Statement

Data are stored in the hospital’s secure database.