Prevalence and Prognostic Implication of Sarcopenia Among Patients With Stage B Heart Failure: The PAPRIKA‐HF Cohort Study

ABSTRACT

Background

The long‐term prognosis of patients with heart failure (HF) remains poor. Most patients with HF are older, and multiple factors involved in geriatric syndromes are associated with worse long‐term prognosis. Sarcopenia is a major component of geriatric syndrome. Early diagnosis and therapeutic intervention for sarcopenia are clinically important in patients with HF; however, the prevalence and long‐term prognostic impact of sarcopenia in patients with stage B HF remain unclear. This study aimed to determine the prevalence of sarcopenia in older patients with stage B HF and its impact on the long‐term prognosis.

Methods

The PAPRIKA‐HF study was a multicenter, prospective study that enrolled outpatients ≥ 65 years who were diagnosed with stage B HF. Sarcopenia was assessed based on the Asian Working Group for Sarcopenia 2019 diagnostic criteria. The primary endpoint was a composite endpoint (all‐cause mortality, incident myocardial infarction, or hospitalization for heart failure) of > 2 years.

Results

Among 312 patients (mean age: 78.2 ± 6.5 years, 45% female), 17.7% (56 of 312 patients) had sarcopenia. The rate of the composite endpoint over 2 years was significantly higher in patients with sarcopenia than in those without (25.0% vs. 2.7%, log‐rank test, p < 0.0001). Multivariate analysis using the Cox proportional hazards model showed that sarcopenia was an independent predictor of long‐term prognosis (hazard ratio: 5.78, 95% confidence interval: 2.16–15.43, p < 0.001).

Conclusions

Sarcopenia was associated with a worse long‐term prognosis in older patients with stage B HF, highlighting the importance of early diagnosis of sarcopenia.

Summary.

• Key points

  • ○
    Among older patients with stage B HF, 17.7% had sarcopenia.
  • ○
    Patients with sarcopenia had a significantly worse prognosis during 2‐year follow‐up than those without sarcopenia, and multivariate analysis using the Cox proportional hazards model revealed that sarcopenia was an independent predictor of long‐term prognosis.
• Why does this paper matter?

  • ○
    In addition to previous findings in patients with stage C HF and beyond, sarcopenia is a worse prognostic factor, even at earlier stages of HF. Early detection of sarcopenia and treatment interventions may help prevent HF progression and improve the long‐term prognosis.

1. Introduction

The prevalence of heart failure (HF) has increased markedly worldwide with the aging of the population [1]. Despite remarkable advances in diagnosis, medication, and interventional therapy, the long‐term prognosis for HF remains poor [1]. This may be due to a combination of geriatric syndromes such as sarcopenia, frailty, and malnutrition, as well as cardiovascular function [2]. Sarcopenia, in particular, is one of the major geriatric syndromes characterized by reduced muscle mass, muscle strength, and physical function. Sarcopenia is part of a continuous process that progresses to frailty and eventually to cachexia [3]. Although cachexia is a progressive condition with poor response to treatment, sarcopenia is a reversible condition [4]. Therefore, early detection of sarcopenia and therapeutic intervention are necessary to control the progression of geriatric syndromes.

Sarcopenia is associated with an increased risk of mortality in patients with stage C HF; however, exercise intervention for sarcopenia contributes insufficiently to improve long‐term survival [5, 6, 7]. In the REHAB‐HF trial, older patients who were hospitalized for acute HF were treated with exercise intervention 6 months after discharge, resulting in significant improvements in physical function and muscle strength, whereas there was no significant improvement in long‐term prognosis [6]. Similarly, in a meta‐analysis by the Cochrane database, exercise intervention did not significantly improve long‐term mortality in patients with stage C HF [7]. This is because these patients often have advanced geriatric conditions, including frailty and cachexia, with marked loss of skeletal muscle, malnutrition, and severe impairment of physical function, limiting the effectiveness of exercise intervention [8].

Based on this background, detection of, and therapeutic interventions for, sarcopenia at an earlier stage, specifically at the stage B HF phase, may help suppress the progression of geriatric syndromes and subsequently prevent HF development and improve long‐term outcomes [9]. Stage B HF, a phase in which patients exhibit cardiac structural abnormalities but no HF symptoms, is a crucial target for risk stratification and preventive strategies. However, no previous study has investigated the prognostic impact of sarcopenia in patients with stage B HF. Accordingly, in the PAPRIKA‐HF study, we aimed to investigate whether sarcopenia is associated with worse prognosis in older patients with stage B HF.

2. Methods

2.1. Study Design and Population

In this observational study, we prospectively enrolled older patients who were diagnosed with stage B HF who visited four centers (two university hospitals, one community hospital, and one clinic) as outpatients between June 2021 and May 2023. The patient enrollment criteria were as follows: age ≥ 65 years, no history of HF hospitalization, and a diagnosis of stage B HF based on symptoms, medical history, and echocardiographic findings. The exclusion criteria were as follows: active malignancy, undergoing dialysis, difficulty performing physical function assessments, and taking diuretics. This study complied with the principles of the 1975 Declaration of Helsinki. Written informed consent was obtained from all the participants. The study protocol was approved by the Ethics Committee of our institute and registered in UMIN‐CTR.

2.2. Data Collection

Data on age, sex, body mass index (BMI), medical history (hypertension, dyslipidemia, diabetes, atrial fibrillation, coronary artery disease, history of myocardial infarction, and history of cardiac surgery), and oral medications were obtained at study enrollment. Laboratory parameters and echocardiographic findings at enrollment were also recorded. Valvular disease was defined as moderate or severe stenosis or regurgitation of the aortic, mitral, or tricuspid valves on echocardiography. Assessment of physical function and bioelectrical impedance analysis (BIA) were performed according to standardized procedures at each center.

2.3. Definition of Stage B HF

Based on the 2022 guidelines of the American College of Cardiology (ACC), American Heart Association (AHA), and Heart Failure Society of America (HFSA), stage B HF was defined as patients with no symptoms or signs of HF but with structural heart abnormalities, cardiac dysfunction, or at risk of developing HF [10]. For structural heart abnormalities, echocardiography was used to determine the Atherosclerosis Risk in Communities (ARIC) criteria (wall motion abnormalities, valvular heart disease, left ventricular enlargement, left ventricular hypertrophy, systolic abnormality or diastolic abnormality) [11].

2.4. Assessment of Sarcopenia

The diagnosis of sarcopenia was based on the definition and diagnostic criteria by the Asian Working Group for Sarcopenia 2019 (AWGS 2019) [12]. The AWGS 2019 defines sarcopenia as a loss of muscle mass, accompanied by loss of muscle strength or physical function. Muscle strength was assessed by measuring the grip strength using a grip strength meter (GRIP‐D; Takei Scientific Instruments Co. Ltd., Niigata, Japan). A grip strength of < 28 kg in men and < 18 kg in women was defined as low muscle strength. Muscle mass was measured using BIA (InBody 720 analyzer; InBody Co. Ltd., Seoul, Korea; mBCA, Seca Nihon, Chiba, Japan). The appendicular skeletal muscle mass index was calculated by dividing the appendicular skeletal muscle mass by the square of height; an appendicular skeletal muscle mass index < 7.0 kg/m² in men and < 5.7 kg/m² in women was defined as low muscle mass. Physical performance was assessed using a 6‐m walk test, 5‐time chair stand test, or short physical performance battery (SPPB). Low physical performance was diagnosed if a patient achieved any one of the following scores: 6‐m walk < 1.0 m/s, 5‐time chair stand test > 12.0 s, or short physical performance battery ≤ 9. Based on the results of the above evaluations, sarcopenia was diagnosed when low muscle mass was combined with low muscle strength or low physical performance.

2.5. Outcome

The primary endpoint was a 2‐year composite endpoint, including all‐cause mortality, myocardial infarction, and hospitalization for HF. The secondary endpoints included all‐cause mortality, myocardial infarction, and hospitalization for HF. Event occurrence was ascertained by reviewing medical records, sending prognostic questionnaires to referring hospitals, or telephone interviews. Myocardial infarction and HF hospitalization were considered events if the American College of Cardiology/American Heart Association Key Data Elements and Definitions for Cardiovascular Endpoint Events in Clinical Trials were fulfilled [13].

2.6. Sample Size

The sample size was calculated based on a previous study that investigated the long‐term impact of sarcopenia on mortality among community‐dwelling older adults [14]. In that study, the prevalence of sarcopenia was 14% (261 of 1851 participants), while the 1‐year all‐cause mortality rates were 103 per 1000 and 19 per 1000 person‐years in the sarcopenia and non‐sarcopenia groups, respectively. Based on these data, we assumed a 2‐year event rate of 206 per 1000 person‐years (20.6%) in the sarcopenia group and 38 per 1000 person‐years (3.8%) in the non‐sarcopenia group for the present study. The allocation ratio between the sarcopenia and non‐sarcopenia groups was set at 1:7 with a two‐sided alpha level of 0.05 and power of 80%. The estimated required sample sizes were 36 and 252 participants in the sarcopenia and non‐sarcopenia groups, respectively. Allowing for a 10% dropout rate, the total required sample size was 320 participants.

2.7. Statistical Analysis

Continuous variables are presented as the mean ± standard deviation, and t‐tests were used for between‐group comparisons. Categorical variables are presented as numbers and percentages, and the χ² test was used. Primary and secondary endpoints and subgroup analyses were estimated using the Kaplan–Meier method, and log‐rank tests were used for between‐group comparisons. Univariate analyses were performed using covariates that showed statistically significant intergroup differences in patient characteristics and laboratory parameters (age; sex; BMI; dyslipidemia; prior cardiac surgery; and hemoglobin; serum albumin; high‐sensitivity C‐reactive protein; and B‐type natriuretic peptide or NT‐pro B‐type natriuretic peptide levels as modifiers). Covariates with values of p < 0.05 on the univariate analysis were subsequently included in the multivariate analysis. The uni‐ and multivariate analyses were performed using a Cox proportional hazards model. Subgroup analyses by sex, renal dysfunction (serum creatinine ≥ or < 1.10 mg/dL), and BMI (≥ or < 22.0 kg/m²) were performed as sensitivity analyses. All analyses were performed using JMP Pro 18.1.0 software (SAS Institute Inc., Cary, NC, USA), with p‐values < 0.05 considered significant.

3. Results

3.1. Patient Background

During the study period, 331 patients were prospectively enrolled in the PAPRIKA‐HF trial. A total of 317 older patients with stage B HF were analyzed after excluding those in whom BIA measurements were unable to be collected or who were missing laboratory data (Supporting Information Figure S1). The mean age of the patients was 78.2 ± 6.5 years, and 45% were female. Based on the AWGS 2019 criteria, 56 (17.7%) patients were diagnosed with sarcopenia (Supporting Information Table S1). Patients with sarcopenia were significantly older, had a greater proportion of females, and had a significantly lower BMI than those without sarcopenia (Table 1). With the exception of dyslipidemia and prior cardiac surgery, the comorbidities were comparable in both groups, as were the prescription rates. The laboratory findings showed that patients with sarcopenia had lower hemoglobin and serum albumin levels and higher levels of high‐sensitivity C‐reactive protein and B‐type natriuretic peptide than patients without sarcopenia (Table 2). Echocardiographic findings showed that the left ventricular ejection fraction and rate of left ventricular asynergy were similar in both groups, while E/e’ was significantly higher in patients with sarcopenia than in those without sarcopenia. The incidence of valvular disease was significantly higher in patients with sarcopenia than in those without sarcopenia.

TABLE 1.

Patient characteristics at admission.

	Sarcopenia (n = 56)	Non‐sarcopenia (n = 261)	p–value
Age (years)	81.3 ± 6.5	77.5 ± 6.3	< 0.0001
Female	37 (66)	107 (41)	< 0.001
BMI (kg/m2)	21.4 ± 3.8	23.7 ± 3.5	< 0.0001
Comorbidity
Hypertension	45 (80)	220 (84)	0.47
Dyslipidemia	31 (55)	189 (72)	0.01
Diabetes mellitus	19 (34)	74 (28)	0.41
Atrial fibrillation	19 (34)	92 (35)	0.85
Prior myocardial infarction	11 (20)	56 (21)	0.76
Prior cardiac surgery	23 (41)	55 (21)	< 0.01
Prescription
ACE‐I/ARB	31 (55)	166 (64)	0.25
Calcium channel blockers	26 (46)	130 (50)	0.65
Thiazides	2 (4)	11 (4)	0.83
Beta blockers	24 (43)	136 (52)	0.21
SGLT2i	6 (11)	23 (9)	0.65
Antiplatelets	29 (52)	131 (50)	0.83
Anticoagulants	15 (27)	94 (36)	0.19

Note: Data presented as mean ± standard deviations or number (%).

Abbreviations: ACE‐I/ARB, angiotensin‐converting enzyme inhibitor/angiotensin II receptor blocker; BMI, body mass index; SGLT2i, sodium‐glucose cotransporter 2 inhibitor.

TABLE 2.

Laboratory and echocardiographic parameters.

	Sarcopenia (n = 56)	Non‐sarcopenia (n = 261)	p–value
Laboratory
Hemoglobin (g/dL)	12.4 ± 1.6	13.2 ± 1.7	< 0.01
Serum creatinine (mg/dL)	0.95 ± 0.43	0.96 ± 0.39	0.87
Serum albumin (g/dL)	4.0 ± 0.4	4.1 ± 0.3	< 0.01
Uric acid (mg/dL)	5.8 ± 1.6	5.4 ± 1.2	0.05
High‐sensitive CRP (mg/dL)	0.65 ± 1.46	0.25 ± 0.78	< 0.01
BNP (pg/mL)	161 ± 141 (n = 48)	92 ± 143 (n = 241)	< 0.01
NT‐pro BNP (pg/mL)	411 ± 233 (n = 3)	568 ± 933 (n = 15)	0.78
Echocardiography
Left atrial diameter (mm)	38 ± 6	40 ± 7	0.25
Left ventricular end‐diastolic diameter (mm)	42 ± 5	45 ± 5	< 0.001
Left ventricular end‐diastolic volume (ml)	74 ± 25	86 ± 28	< 0.01
Left ventricular mass (g)	130 ± 41	142 ± 48	0.09
Left ventricular ejection fraction (%)	65 ± 9	64 ± 9	0.84
E/e′	14.1 ± 6.8 (n = 43)	11.3 ± 3.7 (n = 214)	< 0.001
Left ventricular asynergy	13 (23)	71 (27)	0.53
Valvular disease	20 (36)	40 (15)	< 0.001

Note: Data are presented as median (25th to 75th percentiles) or numbers (%).

Abbreviations: BNP, B‐type natriuretic peptide; CRP, C‐reactive protein.

3.2. Primary Outcome

During the 2‐year follow‐up period, the composite endpoint was observed in 26 patients. Compared to patients without sarcopenia, those with sarcopenia had a significantly higher incidence of the composite endpoint (25.0% [14 of 56 patients] vs. 2.7% [7 of 261 patients], log‐rank test p < 0.0001; Figure 1). Univariate and multivariate analyses using the Cox proportional hazards model were conducted to examine the effect of sarcopenia on the composite endpoints (Table 3). In the univariate analysis, age, dyslipidemia, prior cardiac surgery, hemoglobin level, serum albumin level, high‐sensitivity C‐reactive protein level, and sarcopenia were associated with the composite endpoint. After the adjustment for covariates that were statistically significant in the univariate analysis, sarcopenia was an independent predictor of the composite endpoint (hazard ratio, 5.78; 95% confidence interval, 2.16–15.43; p < 0.001).

FIGURE 1.

Kaplan–Meier analysis of patients who were free of the composite endpoint.

TABLE 3.

Cox proportional hazard model for composite endpoint.

	Unadjusted HR (95% CI)	p‐value	Adjusted HR a (95% CI)	p‐value
Age (years)	1.19 (1.10–1.29)	< 0.0001	1.09 (1.00–1.19)	0.04
Female sex	2.03 (0.84–4.89)	0.12
BMI	0.93 (0.81–1.05)	0.27
Dyslipidemia	0.38 (0.16–0.91)	0.03	0.66 (0.26–1.69)	0.39
Prior cardiac surgery	2.39 (1.01–5.68)	0.04	1.33 (0.45–3.92)	0.60
Hemoglobin (g/dL)	0.66 (0.52–0.84)	< 0.001	0.90 (0.66–1.23)	0.51
Serum albumin (mg/dL)	0.10 (0.03–0.28)	< 0.0001	0.35 (0.11–1.14)	0.08
High‐sensitivity CRP (mg/dL)	1.31 (1.02–1.55)	< 0.01	1.03 (0.81–1.32)	0.80
BNP > 100 pg/mL or NT‐pro BNP > 400 pg/mL	1.97 (0.82–4.74)	0.19
Sarcopenia	10.73 (4.33–26.61)	< 0.0001	5.78 (2.16–15.43)	< 0.001

Abbreviations: BMI, body mass index; BNP, B‐type natriuretic peptide; CI, Confidence interval; CRP, C‐reactive protein; HR, Hazard ratio.

^a Referring to covariates with values of p < 0.05 on the univariate analysis.

3.3. Secondary Outcomes

During the 2‐year follow‐up period, all‐cause mortality was observed in 15 patients, hospitalization for acute myocardial infarction in three, and hospitalization for new‐onset HF in eight. For all secondary outcomes, patients with sarcopenia had a significantly higher incidence than those without sarcopenia (all‐cause death, 19.6% vs. 1.5%, log‐rank test p < 0.0001; acute myocardial infarction, 3.6% vs. 0.4%, log‐rank test p = 0.02; hospitalization for HF, 10.7% vs. 0.8%, log‐rank test p < 0.0001; Supporting Information Table S2).

3.4. Subgroup Analyses

When patients were stratified by sex, the incidence of the composite endpoint was significantly higher for sarcopenia in both subgroups (male: 21.1% [4 of 19 patients] vs. 2.6% [4 of 154 patients], log‐rank test p = 0.0001; female: 27.0% [10 of 37 patients] vs. 2.8% [3 of 107 patients], log‐rank test p < 0.0001) (Figure 2A,B). When the patients were stratified into groups with and without renal dysfunction, the incidence of the composite endpoint was significantly higher for sarcopenia in both groups (patients with renal dysfunction: 28.6% [4 of 14 patients] vs. 1.8% [1 of 56 patients], log‐rank test p < 0.001; patients without renal dysfunction: 23.8% [10 of 42 patients] vs. 2.9% [6 of 205 patients], log‐rank test p < 0.0001) (Figure 2C,D). Patients were stratified by BMI (≥ 22.0 kg/m² and < 22.0 kg/m²), and the incidence of the composite endpoint was significantly higher for sarcopenia in the BMI ≥ 22.0 kg/m² group (BMI ≥ 22.0 kg/m² 33.3% [7 of 21 patients] vs. 0.6% [1 of 183 patients], log‐rank test p < 0.0001), while in the BMI < 22.0 kg/m² group, there was a trend toward higher rates in the sarcopenia group; however, this difference was not statistically significant (BMI < 22.0 kg/m² 20.0% [7 of 35 patients] vs. 7.7% [6 of 78 patients], log‐rank test p = 0.052) (Figure 2E,F).

FIGURE 2.

Subgroup analyses of the development of the composite endpoint using the Kaplan–Meier method. Stratification into subgroups based on sex (A and B), serum creatinine level (C and D), and BMI (E and F). BMI, Body mass index.

4. Discussion

The principal findings of our study were as follows: among older patients with stage B HF, 17.7% had sarcopenia. Patients with sarcopenia had a significantly worse long‐term prognosis than those without sarcopenia, and multivariate analysis using the Cox proportional hazards model revealed that sarcopenia was an independent predictor of long‐term prognosis. In addition to previous findings in patients with stage C HF and beyond, we believe that sarcopenia is a worse prognostic factor, even at earlier stages of HF.

Few studies have addressed the impact of sarcopenia or frailty on the long‐term prognosis of older patients with early‐stage HF [14, 15]. These studies have identified the prognostic impact of sarcopenia and frailty in older patients. Zheng et al. retrospectively analyzed older patients with stage B HF hospitalized in the medical and surgical department [15]. The authors examined the impact of physical frailty on the long‐term prognosis of patients with stage B HF who were clinically ill and required hospitalization. Sarcopenia is a reversible pathology that focuses on muscle mass and physical function, whereas frailty indicates a more vulnerable condition, including not only physical but also body weight loss and fatigue symptoms. Their study targeted a high‐risk population with advanced functional impairments. A retrospective cohort study by Kitamura et al. reported the relationship between sarcopenia and long‐term mortality in community‐dwelling patients aged ≥ 65 years, regardless of HF [14]. As they did not assess cardiac structural abnormalities via echocardiography, they did not classify HF stage. Therefore, the target population varied across stages A–C. In contrast, our study prospectively followed a homogeneous population defined according to diagnostic criteria (ARIC criteria), including echocardiography.

Several underlying mechanisms explain the association between sarcopenia and worse long‐term prognosis in patients with stage B HF. First, decreased physical activity and exercise capacity due to sarcopenia reduce daily activity and worsen physical endurance and circulatory regulatory function [16]. Persistent deterioration of circulatory regulatory function accelerates the decline of cardiac function and increases the risk of manifestation of clinical HF. In our study, patients with sarcopenia had elevated E/e’ and B‐type natriuretic peptide levels, suggesting a potential decline in cardiac function. Second, sarcopenia is associated with persistent increases in inflammatory cytokines (e.g., IL‐6, TNF‐α), and chronic inflammation enhances muscle protein degradation and inhibits protein synthesis [8]. Chronic inflammation also affects the pathogenesis of HF, which can be mutually exacerbated via common pathways (e.g., NF‐κB, JAK–STAT). In our study, patients with sarcopenia had significantly higher levels of high‐sensitivity C‐reactive protein, suggesting that chronic inflammation may be underlying. Additionally, age‐related declines in anabolic hormones (e.g., testosterone, IGF‐1, DHEA) also contribute to the progression of sarcopenia and reduce myocardial repair capacity and metabolic function [17, 18]. Thus, common endocrine and immunological pathways mediate the development of sarcopenia and HF. Third, in older patients, anorexia, poor swallowing function, and depression lead to decreased food intake, frequently resulting in chronic energy and protein deficiency [19]. These conditions suppress muscle protein synthesis and make it difficult to maintain physical function. Additionally, malnutrition adversely affects myocardial energy metabolism, contributing to reduced myocardial contractility through inefficient ATP production and mitochondrial damage [20]. Thus, poor nutritional status may negatively affect both muscle and cardiac function, contributing to a worse prognosis. In our study, patients with sarcopenia had significantly lower BMI, hemoglobin, and serum albumin levels, suggesting that a low nutritional status may exist. Fourth, in sarcopenic patients with HF, chronic congestion and hypoperfusion lead to metabolic disturbances [21]. These metabolic disturbances increase skeletal muscle proteolysis and cause further loss of muscle mass and strength. Hence, skeletal muscle and cardiac function are not impaired in isolation, but form a negative chain structure that adversely affects each other through a pathological inter‐organic network. Based on the above mechanisms, sarcopenia may affect the cardiovascular system and be associated with a worse prognosis.

4.1. Strengths and Limitations

To date, most studies on the long‐term prognosis of sarcopenia have focused on community‐dwelling patients with stage C HF. Our study demonstrates the importance of risk assessment in the early and preventable stages of B HF. Sarcopenic patients with stage B HF are considered to be at high risk; therefore, interventions to treat sarcopenia through cardiac rehabilitation, nutritional intervention, and social support are crucial. Although there are no reports on the effectiveness of therapeutic intervention for sarcopenia in patients with stage B HF, and the effect of therapeutic intervention on long‐term prognosis is unknown, the effectiveness of cardiac rehabilitation on long‐term prognosis in patients with coronary heart disease has been reported. Therefore, therapeutic intervention for stage B HF is considered potentially effective [22]. However, it is not feasible to provide sustained cardiac rehabilitation for all patients with coronary artery disease. Indeed, the reported outpatient cardiac rehabilitation uptake rate in Japan for patients with acute coronary syndrome is 7.9%, indicating the difficulty of implementing cardiac rehabilitation interventions in an outpatient setting [23]. The assessment of sarcopenia in patients with stage B HF may help identify a high‐risk population that needs to be introduced to aggressive cardiac rehabilitation. In our study, echocardiography was performed before patient enrollment, and stage B was strictly defined by the presence of structural heart disease based on the ARIC criteria. Furthermore, patients with active malignancies and those undergoing dialysis were excluded, providing a homogeneous target population with reduced confounding factors that enhanced the internal validity of the study. In addition, our study included patients from university hospitals, community hospitals, and clinics to ensure external validity in accordance with the actual medical environment.

Our study has some limitations. First, the reliability of the subgroup analyses was limited by the small sample size and low number of events in each subgroup. However, these analyses were exploratory in nature and unable to detect definitive interactions. Therefore, the results of these subgroup analyses should be interpreted with caution, and hypothesis generation should be considered with confirmation in larger, adequately powered studies. Second, although we adjusted for clinical covariates that significantly differed between the sarcopenia and non‐sarcopenia groups, residual confounding factors may persist. In particular, we did not include other geriatric syndromes, such as frailty, cognitive impairment, or depressive symptoms, that may be closely related to sarcopenia and long‐term outcomes. Additionally, the relatively high hazard ratio observed in this study may reflect an overestimation of the effect size due to the limited number of events and small sample size. Therefore, these findings should be interpreted with caution and further studies with larger cohorts and comprehensive geriatric assessments performed. Third, compared to dual X‐ray absorptiometry, the BIA used in this study probably underestimated lean body mass, although the direct‐fractionated multifrequency BIA was found to be acceptably accurate [24]. Fourth, the prevalence of sarcopenia is not representative of the general population because only a subset of patients who visited the hospital as outpatients were registered. Finally, because the number of registered patients was limited to Japan, future validation in other regions is needed. Despite these limitations, this study is the first to evaluate the impact of sarcopenia on long‐term prognosis in older patients with stage B HF, and we believe that it has clinical relevance in demonstrating the importance of assessing sarcopenia in the early stages of HF.

5. Conclusions

Our results revealed that 17.7% of older patients with stage B HF had sarcopenia and that patients with sarcopenia had a significantly higher incidence of the 2‐year composite endpoint. The Cox proportional hazards model showed that sarcopenia was a predictive factor of poor prognosis. Early detection of sarcopenia and treatment interventions may help prevent HF progression and improve the long‐term prognosis.

Author Contributions

K.M., Y.K., and G.N. conceived and designed this study. S.M., J.M., S.K., S.H., E.Y., and M.U. contributed to data collection and analyses. All authors contributed to the interpretation of the results and revision of the manuscript for important intellectual content, and approved the final version of the manuscript. The authors assume full responsibility for the data analyses and interpretation. The corresponding author attests that all listed authors meet the authorship criteria and that no others meeting the criteria have been omitted.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Table S1: Physical parameters. Data presented as mean ± standard deviations.SPPB, Short physical performance battery.

Table S2: Incidence of clinical events. Data are presented as n (%).

Figure S1: Study flowchart. BIA, bioelectrical impedance analysis; HF, heart failure.

Matsumura K., Morishita S., Morimoto J., et al., “Prevalence and Prognostic Implication of Sarcopenia Among Patients With Stage B Heart Failure: The PAPRIKA‐HF Cohort Study,” Journal of the American Geriatrics Society 73, no. 10 (2025): 3105–3112, 10.1111/jgs.70046.