Frailty, Sarcopenia, Cachexia, and Malnutrition in Heart Failure.

With global aging, the number of patients with heart failure has increased markedly. Heart failure is a complex condition intricately associated with aging, organ damage, frailty, and cognitive decline, resulting in a poor prognosis. The relationship among frailty, sarcopenia, cachexia, malnutrition, and heart failure has recently received considerable attention. Although these conditions are distinct, they often exhibit a remarkably close relationship. Overlapping diagnostic criteria have been observed in the recently proposed guidelines and position statements, suggesting that several of these conditions may coexist in patients with heart failure. Therefore, a comprehensive understanding of these conditions is essential, and interventions must not only target these conditions individually, but also provide comprehensive management strategies. This review article provides an overview of the epidemiology, diagnostic methods, overlap, and prognosis of frailty, sarcopenia, cachexia, and malnutrition in patients with heart failure, incorporating insights from the FRAGILE-HF study data. Additionally, based on existing literature, this article discusses the impact of these conditions on the effectiveness of guideline-directed medical therapy for patients with heart failure. While recognizing these conditions early and promptly implementing interventions may be advantageous, further data, particularly from well-powered, large-scale, randomized controlled trials, are necessary to refine personalized treatment strategies for patients with heart failure.

Bendopnea prevalence and prognostic value in older patients with heart failure: FRAGILE-HF-SONIC-HF post hoc analysis.

AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS: This post hoc analysis was performed using two prospective, multicenter, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. RESULTS: Among the 1,243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8% and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.18-3.78, P = 0.012) and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSIONS: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

This study investigated how common it is for older patients with heart failure to have trouble breathing when they bend forward, and whether this affects their chances of survival. The study found that although this problem is not very common, it is linked to a higher risk of death. Key findings: Only a small number of older patients with heart failure have trouble breathing when they bend forward.However, those who do have this problem are more likely to die.

Nutrition Assessment and Education of Patients with Heart Failure by Cardiologists.

Although nutritional assessment and education are important for hospitalized patients with heart failure, the extent of their implementation in real-world clinical practice is unknown. Therefore, this study aimed to investigate the evaluation and management of nutrition during hospitalization for heart failure using a questionnaire survey for cardiologists.In this cross-sectional multicenter survey, 147 cardiologists from 32 institutions completed a web-based questionnaire (response rate, 95%).The survey showed that 78.2% of the respondents performed a nutritional assessment for hospitalized patients, whereas 38.3% used objective tools. In contrast, only 9.5% of the respondents evaluated the presence or absence of cardiac cachexia. Most respondents (89.8%) reported providing nutritional education to their patients before hospital discharge. However, compared with the number of respondents who provided information on sodium (97.0%) and water (63.6%) restrictions, a limited number of respondents provided guidance on optimal protein (20.5%) and micronutrient (9.1%) intake as part of the nutritional education. Less than 50% of the respondents provided guidance on optimal calorie intake (43.2%) and ideal body weight (34.8%) as a part of the nutritional education for patients identified as malnourished.Although nutritional assessment is widely performed for hospitalized patients with heart failure, most assessments are subjective rather than objective. Nutritional education, frequently provided before hospital discharge, is limited to information on water or salt intake restrictions. Therefore, more comprehensive and individualized nutritional assessments and counselling with a scientific basis are required.

Predictive value of the Ishii score for sarcopenia and the prognosis of older patients hospitalized with heart failure.

AIMS: Although sarcopenia is common and associated with poor outcomes in patients with heart failure, its simple screening methods remain unclear. We aimed to investigate the predictive value of the Ishii score, which includes age, grip strength, and calf circumference, for sarcopenia and its prognostic predictability in patients with heart failure. METHODS: This was a subanalysis of the FRAGILE-HF study. Receiver operating characteristic curves were used to evaluate the predictive value for sarcopenia. Patients were stratified into the high and low Ishii score groups based on the cutoff values of the Ishii score determined by the Youden index for sarcopenia, and the 1-year mortality rates were compared. RESULTS: Of the 1262 study participants, 936 were evaluated with sarcopenia, and 184 (55 women, 129 men) were diagnosed with sarcopenia. The areas under the receiver operating characteristic curves for sarcopenia were 0.73 and 0.87 for women and men, respectively. The optimal cutoff values for predicting sarcopenia were 165 and 141 for women and men, respectively. Using these cutoff values, the sensitivity and specificity for sarcopenia were 70.9% and 68.5% for women and 88.4% and 69.7% for men, respectively. At 1 year, 151 (low Ishii score group, 98; high Ishii score group, 53) deaths were observed. Adjusted Cox proportional hazards analysis showed that the high Ishii score group was significantly associated with 1-year mortality. CONCLUSION: Among older patients hospitalized for heart failure, the Ishii score is useful for predicting sarcopenia and 1-year mortality. Geriatr Gerontol Int 2024; 24: 147-153.

A Case Report of Mixed-type Dyspnoea Diagnosed via Non-invasive and Invasive Cardiopulmonary Exercise Tests.

A gas exchange analysis with the cardiopulmonary exercise test is effective in discriminating non-cardiogenic components of limited exercise tolerance and is important for use in combination with the diastolic stress test. An 80-year-old woman with progressive exertional dyspnoea, hypertension, and untreated bronchial asthma was diagnosed with heart failure with a preserved ejection fraction by invasive testing. Diuretics were initiated, which resulted in partial symptom improvement. A subsequent non-invasive test revealed a reduced breathing reserve, suggesting exertional dyspnoea complications linked to lung disease. Bronchodilators were administered, which further improved the symptoms.

Poor Increase in Pulse Pressure During Cardiopulmonary Exercise Testing Predicts Cardiovascular Death of Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: The increase in stroke volume during inotropic stimulation in patients with heart failure with reduced ejection fraction (HFrEF) is called the "pump function reserve." Few studies have reported on the relationship between pump function reserve and HF prognosis. In HFrEF patients who have pump function reserve, stroke volume increases during exercise. Simply put, the pulse pressure change (∆PP) during cardiopulmonary exercise testing (CPX) is closely related to the prognosis of patients with HFrEF. We hypothesized that ∆PP could predict disease severity and cardiovascular death in patients with HFrEF.Methods and Results:A total of 224 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016 were enrolled. During a median follow-up of 1.5 years, cardiovascular death occurred in 54 participants (24%). Patients who died demonstrated a lower ∆PP between rest and peak exercise (∆PP [peak-rest]) than those who survived (P<0.001). Cox regression analyses revealed that ∆PP, slope of the relationship between minute ventilation and carbon dioxide production, and B-type natriuretic peptide level were independent predictors of cardiovascular death in patients with HFrEF (P=0.001, 0.021, and <0.001, respectively). CONCLUSIONS: ∆PP (peak-rest) can accurately predict cardiovascular death in patients with HFrEF and may be a useful new prognostic indicator in these patients.

Relationship between ventilatory pattern and peak VO2 and area M regulates the respiratory system during exercise.

BACKGROUND: Exertional dyspnea is a major symptom of heart failure. We investigated the tidal volume (TV)-the respiratory rate (RR) regulation according to the peak O2 uptake (VO2) during cardiopulmonary exercise testing (CPET) for clarifying exercise ventilatory pattern. METHODS: We enrolled 1111 patients (66±13 years old, 68% men) who had undergone CPET at our hospital. We investigated the relationship between TV and RR and drew the TV/height-RR figure according to the %peak VO2. RESULTS: During exercise, TV was greater, illustrated as higher %peak VO2. However, RR was weakly correlated with %peak VO2. Adjusted with age, height, sex, each point of RR, and %peak VO2, TV during exercise highly correlated with age, height, each point of RR, and % peak VO2 (R=0.726 to 0.821, p<0.01). In the figure, regardless of the %peak VO2, TV/height and RR values were linearly related at rest, as well as at the point of anaerobic threshold, respiratory compensation, and peak exercise point, with each of these lines converging onto a single area (area M). The TV-RR slope values at early phase were also lower at lower %peak VO2. CONCLUSIONS: We identified three ventilatory regularities during exercise. First, TV increases as greater %peak VO2. Second, the line relating TV/height and RR at each reference point during the incremental exercise test converged onto area M. Finally, the TV-RR slope at the early exercise phase was lower in patients with a lower %peak VO2. These ventilatory regularities may assist in elucidating the excise ventilatory pattern and help the diagnosis of exertional dyspnea.

Relationship Between Respiratory Compensation Point and Anaerobic Threshold in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Cardiopulmonary exercise testing (CPX) is used in the prognostic evaluation of patients with heart failure with reduced ejection fraction (HFrEF). In these patients, the ventilation feedback system is dysfunctional, and overactive peripheral chemoreceptors may be responsible for the early appearance of the respiratory compensation point (RCP) after the anaerobic threshold (AT). The mechanism of RCP appearance remains unknown and very few studies have reported the relationship between RCP and heart failure. We hypothesized that the duration between the RCP and AT (RCP-AT time) can predict the severity of cardiac disorders and prognosis in patients with HFrEF.Methods and Results:We enrolled 143 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016. During a median follow-up of 1.4 years, cardiovascular death occurred in 45 participants (31%). The patients who died had a significantly shorter RCP-AT time and lower hemoglobin (Hb) levels than those who survived (P<0.001 and P=0.01, respectively). Cox regression analyses revealed RCP-AT time and Hb level to be independent predictors of cardiovascular death in patients with HFrEF (P<0.001 and P=0.018, respectively). CONCLUSIONS: RCP-AT time can better predict prognosis in patients with HFrEF than the magnitude of increase in oxygen consumption within the isocapnic buffering domain (∆V̇O2AT-RCP). It may be useful as a new prognostic indicator in these patients.

Ventilatory Efficacy After Transcatheter Aortic Valve Replacement Predicts Mortality and Heart Failure Events in Elderly Patients.

BACKGROUND: We aimed to clarify the predictors of death or heart failure (HF) in elderly patients who undergo transcatheter aortic valve replacement (TAVR).Methods and Results:We prospectively enrolled 83 patients (age, 83±5 years) who underwent transthoracic echocardiography (TTE) and cardiopulmonary exercise testing (CPET) with impedance cardiography post-TAVR. We investigated the association of TTE and CPET parameters with death and the combined outcome of death and HF hospitalization. Over a follow-up of 19±9 months, peak oxygen uptake (V̇O2) was not associated with death or the combined outcome. The minimum ratio of minute ventilation (V̇E) to carbon dioxide production (V̇CO2) and the V̇E vs. V̇CO2slope were higher in patients with the combined outcome. After adjusting for age, sex, Society of Thoracic Surgeons score and peak V̇O2, ventilatory efficacy parameters remained independent predictors of the combined outcome (minimum V̇E/V̇O2: hazard ratio, 1.108; 95% confidence interval, 1.010-1.215; P=0.031; V̇E vs. V̇CO2slope: hazard ratio, 1.035; 95% confidence interval, 1.001-1.071; P=0.044), and had a greater area under the receiver-operating characteristic curve. The V̇E vs. V̇CO2slope ≥34.6 was associated with higher rates of the combined outcome, as well as lower cardiac output at peak work rate during CPET. CONCLUSIONS: In elderly patients, lower ventilatory efficacy post-TAVR is a predictor of death and HF hospitalization, reflecting lower cardiac output at peak exercise.

Relationship Between Exercise Oscillatory Ventilation Loop and Prognosis of Heart Failure.

BACKGROUND: The cardiopulmonary exercise test (CPX) is a tool for evaluating disease severity and limitations in activities of daily living in patients with cardiac disorders. However, few studies have evaluated the association between exercise oscillatory ventilation (EOV) severity and prognosis in heart failure (HF) patients with EOV. EOV severity can be evaluated by detecting endtidal CO2pressure (PETCO2, an indicator of the arterial partial pressure of CO2(PaCO2)) and minute ventilation, which is a reflection of the respiratory response to elevated CO2. We hypothesized that the magnitude of EOV severity can predict the severity and prognosis of cardiac disorders and aimed to validate this hypothesis.Methods and Results:In total, 2,043 patients who underwent symptom-limited maximal CPX between 2010 and 2016 were evaluated. We enrolled 70 patients who had HF with reduced ejection fraction (HFrEF) and EOV. The endpoint was cardiovascular death. During a median follow-up of 4.3 years, 34 participants died (48%). Those who died showed significantly larger EOV loop size and lower hemoglobin (Hb) levels than those who survived (17.3±7.0 cm2vs. 12.8±6.1 cm2, P<0.001; 12.2±1.2 g/dL vs. 13.2±2.9 g/dL, P=0.004). Cox regression analyses revealed Hb levels and EOV loop size as independent predictors of cardiovascular death in HFrEF patients with EOV. CONCLUSIONS: EOV loop size was associated with cardiovascular death of HFrEF patients with EOV.

Characteristics of patients with a relatively greater minimum VE/VCO2 against peak VO2% and impaired exercise tolerance.

PURPOSE: Cardiopulmonary exercise testing (CPX) is used to evaluate functional capacity and assess prognosis in cardiac patients. Ventilatory efficiency (VE/VCO2) reflects ventilation-perfusion mismatch; the minimum VE/VCO2 value (minVE/VCO2) is representative of pulmonary arterial blood flow in individuals without pulmonary disease. Usually, minVE/VCO2 has a strong relationship with the peak oxygen uptake (VO2), but dissociation can occur. Therefore, we investigated the relationship between minVE/VCO2 and predicted peak VO2 (peak VO2%) and evaluated the parameters associated with a discrepancy between these two parameters. METHODS: A total of 289 Japanese patients underwent CPX using a cycle ergometer with ramp protocols between 2013 and 2014. Among these, 174 patients with a peak VO2% lower than 70% were enrolled. Patients were divided into groups based on their minVE/VCO2 [Low group: minVE/VCO2 < mean - SD (38.8-5.6); High group: minVE/VCO2 > mean + SD (38.8 + 5.6)]. The characteristics and cardiac function at rest, evaluated using echocardiography, were compared between groups. RESULTS: The High group had a significantly lower ejection fraction, stroke volume, and cardiac output, and higher brain natriuretic peptide, tricuspid regurgitation pressure gradient, right ventricular systolic pressure, and peak early diastolic LV filling velocity/peak atrial filling velocity ratio compared with the Low group (p's < 0.01). In addition, the Low group had a significantly higher prevalence of pleural effusion than did the High group (26 vs 11%, p < 0.01). CONCLUSIONS: Patients with a relatively greater minVE/VCO2 in comparison with peak VO2 had impaired cardiac output as well as restricted pulmonary blood flow increase during exercise, partly due to accumulated pleural effusion.