Diagnostic and therapeutic practice for HFpEF across continents and regions: An international survey.

AIMS: This study aims to evaluate the worldwide variations in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF), using an HF survey distributed internationally to physicians, including both cardiologists and non-cardiologists. METHODS AND RESULTS: A group of HF specialists designed an independent, academic web-based survey focusing on HFpEF care and diagnosis, which was distributed via scientific societies and various social networks between 1 May 2023 and 1 July 2023. The survey included 1459 physicians (1242 cardiologists and 217 non-cardiologists) from 91 countries, with a mean age of 42 (34-49) years and 61% male. Most physicians (89.2%) defined HFpEF as left ventricular ejection fraction ≥50%. Significant regional variations were observed in HFpEF management (P < 0.001 for all comparisons unless stated otherwise). Cardiologists managed 63.1% of HFpEF patients overall, with significant variability across regions (P < 0.001). The estimated HFpEF prevalence was highest in Eastern Asia and Western Europe and lowest in Africa and South America. Diagnostic practices varied: natriuretic peptide use ranged from 70%-74% in Africa to 95%-97% in Southern/Western Europe. Echocardiographic parameters showed regional differences, with diastolic stress testing used most in South-Eastern Asia (47% vs. 13-36% elsewhere). HFpEF scoring systems were most common in South-Eastern Asia (78%) and least in Africa (30.1%). Coronary artery disease screening approaches differed, with Eastern Asian physicians more likely to always perform routine angiograms (52%) compared with Northern Europeans (12%). Treatment preferences also varied regionally. Sodium glucose co-transporter-2 inhibitors (SGLT2i) was the preferred first-line treatment (45%-70% across regions), followed by diuretics. In an ideal setting, 52% would primarily use SGLT2i, 33% loop diuretics, and 22% beta-blockers. Drug availability differed significantly: SGLT2i was most available (88% overall), while ARNI was least available (61%). South America and Middle Eastern/Northern Africa reported lower availability of guideline-directed therapies. Multidisciplinary HF programmes were most common in Asia (70%) and least in Africa (24%). The perceived benefit of atrial flow regulator devices also showed significant regional differences. CONCLUSIONS: There are considerable global variations in the diagnosis and management of HFpEF. Most physicians favour SGLT2i despite regional disparities in health care resources and guideline adherence. Harmonized practices and improved access to comprehensive care can enhance outcomes of HFpEF patients worldwide.

Usefulness of hypochloremia at the time of discharge to predict prognosis in patients with chronic heart failure after hospitalization.

BACKGROUND: Hypochloremia has been suggested as a strong marker of mortality in hospitalized patients with heart failure (HF). This study aimed to clarify whether incorporating hypochloremia into pre-existing prognostic models improved the performance of the models. METHODS: We tested the prognostic value of hypochloremia (<97 mEq/L) measured at discharge in hospitalized patients with HF registered in the REALITY-AHF and NARA-HF studies. The primary outcome was 1-year mortality after discharge. RESULTS: Among 2496 patients with HF, 316 (12.6 %) had hypochloremia at the time of discharge, and 387 (15.5 %) deaths were observed within 1 year of discharge. The presence of hypochloremia was strongly associated with higher 1-year mortality compared to those without hypochloremia (log-rank: p < 0.001), and this association remained even after adjustment for the Get With the Guideline-HF risk model (GWTG-HF), anemia, New York Heart Association (NYHA) classification, and log-brain natriuretic peptide (BNP) [hazard ratio (HR) 1.64; p < 0.001]. Furthermore, adding hypochloremia to the prediction model composed of GWTG-HF + anemia + NYHA class + log-BNP yielded a numerically larger area under the curve (0.740 vs 0.749; p = 0.059) and significant improvement in net reclassification (0.159, p = 0.010). CONCLUSIONS: Incorporating the presence of hypochloremia at discharge into pre-existing risk prediction models provides incremental prognostic information for hospitalized patients with HF.

Prevalence and Prognostic Implications of Changes in Tricuspid Regurgitation Severity in Acute Heart Failure.

BACKGROUND: Tricuspid regurgitation (TR), prevalent in acute heart failure (AHF), has a poor prognosis; however, the dynamics of TR severity during hospitalization and its prognostic implications remain unclear. We investigated TR dynamism during hospitalization and its prognostic impact in AHF. METHODS AND RESULTS: This is a post hoc analysis of a prospective multicenter study of patients with AHF who underwent echocardiographic TR severity evaluation at admission and before discharge. The primary end point was a combined of 1-year all-cause mortality and HF rehospitalization after discharge. Among 1079 participants, TR severity changed dynamically, with 60.3% of those with moderate TR and 29.6% of those with severe TR at admission being diagnosed as no or mild TR at discharge. In 3 groups stratified by changes in TR severity, the persistent TR groups had a higher incidence of the primary end point than the resolution and absence groups. In adjusted analyses, the persistent group (hazard ratio, 1.37; 95% confidence interval, 1.04-1.80), but not the resolution group (hazard ratio, 1.07; 95% confidence interval, 0.79-1.44), had a higher primary end point incidence than the absence group. CONCLUSIONS: TR severity at admission in patients with AHF can change dynamically and is associated with subsequent prognosis. Significant TR that remains even after decongestive therapy might be a target for further treatment in hospitalized patients with AHF.

In-hospital initiation of angiotensin receptor-neprilysin inhibition in acute heart failure: the PREMIER trial.

BACKGROUND AND AIMS: The efficacy and safety of early sacubitril/valsartan (Sac/Val) initiation after acute heart failure (AHF) has not been demonstrated outside North America. The present study aimed to evaluate the effect of in-hospital Sac/Val therapy initiation after an AHF episode on N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in Japanese patients. METHODS: This was an investigator-initiated, multicentre, prospective, randomized, open-label, blinded-endpoint pragmatic trial. After haemodynamic stabilization within 7 days after hospitalization, eligible inpatients were allocated to switch from angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to Sac/Val (Sac/Val group) or to continue angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (control group). The primary efficacy endpoint was the 8-week proportional change in geometric means of NT-proBNP levels. RESULTS: A total of 400 patients were equally randomized, and 376 (median age 75 years, 31.9% women, de novo heart failure rate 55.6%, and median left ventricular ejection fraction 37%) were analysed. The per cent changes in NT-proBNP level geometric means at Weeks 4/8 were -35%/-45% (Sac/Val group) and -18%/-32% (control group), and their group ratio (Sac/Val vs. control) was 0.80 (95% confidence interval 0.68-0.94; P = .008) at Week 4 and 0.81 (95% confidence interval 0.68-0.95; P = .012) at Week 8, respectively. In the pre-specified subgroup analyses, the effects of Sac/Val were confined to patients with a left ventricular ejection fraction < 40% and were more evident in those in sinus rhythm and taking mineralocorticoid receptor antagonists. No adverse safety signal was evident. CONCLUSIONS: In-hospital Sac/Val therapy initiation in addition to contemporary recommended therapy triggered a greater NT-proBNP level reduction in Japanese patients hospitalized for AHF. These findings may expand the evidence on Sac/Val therapy in this clinical situation outside North America. CLINICAL TRIAL REGISTRATION: ClinicalTrial.gov (NCT05164653) and Japan Registry of Clinical Trials (jRCTs021210046).

Diagnostic and therapeutic practice for Heart Failure with preserved ejection fraction around the world: An international survey.

BACKGROUND AND AIMS: There is a gap in knowledge about implementing diagnostic tools and therapy for heart failure with preserved ejection fraction (HFpEF) in clinical practice. This survey aimed to assess real-world practice in HFpEF diagnosis and treatment in the international medical community. METHODS: An independent academic web-based 29-question survey was designed by a group of heart failure specialists and posted by email and through scientific societies and social networks to a broad community of physicians worldwide. RESULTS: 1.460 physicians from 95 countries answered the survey, with a mean age of 42.2±10.4 years, 39.4 % females, and 85.1 % were cardiologists. The left ventricular ejection fraction cut-off value selected for HFpEF diagnosis was 50 % for 89 % of participants. The scores for the probability of diagnosis of HFpEF were used only by 47.2 %, and H2FPEF was the most used score (31 %). Natriuretic peptides were used by 87.4 % of participants for the diagnostic workup, while the diastolic stress test was only used by 26.2 %. 54.4 % of participants chose SGLT2 inhibitors as their first drug treatment, followed by diuretics (18.6 %) and ACE inhibitors (8.4 %). CONCLUSIONS: In an international academic survey on HFpEF management, the criteria for screening and diagnosis of HFpEF patients remain aligned with classic international guidelines with a low use of diagnostic scores. SGLT2i is the leading therapeutic drug class used for this heterogeneous patient population. These results raise the need to improve education and awareness on diagnosing and managing HFpEF patients.

Differences in heart failure with preserved ejection fraction management between care providers: an international survey.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by growing incidence and poor outcomes. A large majority of HFpEF patients are cared by non-cardiologists. The availability of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as recommended therapy raises the importance of prompt and accurate identification and treatment of HFpEF across diverse healthcare settings. We evaluated HFpEF management across specialties through a survey targeting cardiologists, HF specialists, and non-cardiologists. METHODS AND RESULTS: An independent web-based survey was distributed globally between May and July 2023. We performed a post-hoc analysis, comparing cardiologists, HF specialists, and non-cardiologists. A total of 1460 physicians (61% male, median age 41[34-49]) from 95 countries completed the survey; 20% were HF specialists, 65% cardiologists, and 15% non-cardiologists. Compared with HF specialists, non-cardiologists and cardiologists were less likely to use natriuretic peptides (p = 0.003) and HFpEF scores (p = 0.004) for diagnosis, and were also less likely to have access to or consider specific echocardiographic parameters (p < 0.001) for identifying HFpEF. Diastolic stress tests were used in less than 30% of the cases, regardless of the specialty (p = 1.12). Multidrug treatment strategies were similar across different specialties. While SGLT2i and diuretics were the preferred drugs, angiotensin receptor blockers and angiotensin receptor-neprilysin inhibitors were the least frequently prescribed in all three groups. However, when constrained to choose one drug, the proportion of physicians favoring SGLT2i varied significantly among specialties (66% HF specialists, 52% cardiologists, 51% non-cardiologists). Additionally, 10% of non-cardiologists and 8% of cardiologists considered beta blocker the drug of choice for HFpEF. CONCLUSION: Significant differences among specialty groups were observed in HFpEF management, particularly in the diagnostic work-up. Our results highlight a substantial risk of underdiagnosis and undertreatment of HFpEF patients, especially among non-HF specialists.

Impact of the MitraClip G4 System on Routine Practice and Outcomes in Patients With Secondary Mitral Regurgitation.

BACKGROUND: The MitraClip G4 system is a new iteration of the transcatheter edge-to-edge repair system. We assessed the impact of the G4 system on routine practice and outcomes in secondary mitral regurgitation (2°MR).Methods and Results: Consecutive patients with 2°MR treated with either the MitraClip G2 (n=89) or G4 (n=63) system between 2018 and 2021 were included. Baseline characteristics, procedures, and outcomes were compared. Inverse probability of treatment weighting and Cox regression were used to adjust for baseline differences. Baseline characteristics were similar, except for a lower surgical risk in the G4 group (Society of Thoracic Surgeons Predicted Risk of Mortality ≥8: 38.1% vs. 56.2%; P=0.03). In the G4 group, more patients had short (≤2 mm) coaptation length (83.7% vs. 54.0%; P<0.001) and fewer clips were used (17.5% vs. 36.0%; P=0.02). Acceptable MR reduction was observed in nearly all patients, with no difference between the G4 and G2 groups (100% vs. 97.8%, respectively; P=0.51). The G4 group had fewer patients with high transmitral gradients (>5mmHg; 3.3% vs. 13.6%; P=0.03). At 1 year, there was no significant difference between groups in the composite endpoint (death or heart failure rehospitalization) after baseline adjustment (10.5% vs. 20.2%; hazard ratio 0.39; 95% confidence interval 0.11-1.32; P=0.13). CONCLUSIONS: The G4 system achieved comparable device outcomes to the early-generation G2, despite treating more challenging 2°MR with fewer clips.

Relevant adverse events and drug discontinuation of sacubitril/valsartan in a real-world Japanese cohort: REVIEW-HF registry.

BACKGROUND: The characteristics, tolerability, and outcomes in patients with heart failure (HF) who are treated with sacubitril/valsartan remain unclear in Japan. METHODS: We conducted a nationwide multicenter study to evaluate the features and outcomes of patients newly prescribed sacubitril/valsartan for the management of HF. We analyzed adverse events (AEs) related to sacubitril/valsartan at 3 months, which were defined as hypotension, worsening renal function, hyperkalemia, and angioedema. Additionally, the association between AEs and outcomes was examined. RESULTS: Among 993 patients, the mean age was 70 years and 291 (29.3 %) were female, and 22.8 % had left ventricular ejection fraction ≥50 %. Of them, 20.8 % had systolic blood pressure (sBP) <100 mmHg, and 19.5 % had estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 at baseline, which were the populations excluded from the eligibility in landmark trials. AEs related to sacubitril/valsartan were observed in 22.5 % of the patients at 3 months. Overall, 22.6 % of patients discontinued sacubitril/valsartan, and hypotension was the most common event leading to drug discontinuation. After adjustment, patients who had worse HF symptoms (New York Heart Association III or IV), sBP <100 mmHg, and eGFR <30 ml/min/1.73 m2 were associated with a higher risk of AEs related to sacubitril/valsartan. Additionally, patients experiencing AEs had a higher risk of cardiovascular death or HF hospitalization than those who did not. CONCLUSION: In Japan, sacubitril/valsartan was also prescribed to patients not eligible for landmark trials, and AEs were observed at a relatively high rate from soon after treatment initiation. Physicians should closely monitor patients for these events, especially in patients anticipated to have a higher risk of AEs.

Evaluation of the efficacy and safety of an integrated telerehabilitation platform for home-based cardiac REHABilitation in patients with heart failure (E-REHAB): protocol for a randomised controlled trial.

INTRODUCTION: Cardiac rehabilitation (CR) is strongly recommended as a medical treatment to improve the prognosis and quality of life of patients with heart failure (HF); however, participation rates in CR are low compared with other evidence-based treatments. One reason for this is the geographical distance between patients' homes and hospitals. To address this issue, we developed an integrated telerehabilitation platform, RH-01, for home-based CR. We hypothesised that using the RH-01 platform for home-based CR would demonstrate non-inferiority compared with traditional centre-based CR. METHODS AND ANALYSIS: The E-REHAB trial aims to evaluate the efficacy and safety of RH-01 for home-based CR compared with traditional centre-based CR for patients with HF. This clinical trial will be conducted under a prospective, randomised, controlled and non-inferiority design with a primary focus on HF patients. Further, to assess the generalisability of the results in HF to other cardiovascular disease (CVD), the study will also include patients with other CVDs. The trial will enrol 108 patients with HF and 20 patients with other CVD. Eligible HF patients will be randomly assigned to either traditional centre-based CR or home-based CR in a 1:1 fashion. Patients with other CVDs will not be randomised, as safety assessment will be the primary focus. The intervention group will receive a 12-week programme conducted two or three times per week consisting of a remotely supervised home-based CR programme using RH-01, while the control group will receive a traditional centre-based CR programme. The primary endpoint of this trial is change in 6 min walk distance. ETHICS AND DISSEMINATION: The conduct of the study has been approved by an institutional review board at each participating site, and all patients will provide written informed consent before entry. The report of the study will be disseminated via scientific fora, including peer-reviewed publications and presentations at conferences. TRIAL REGISTRATION NUMBER: jRCT:2052200064.

Rationale and design of an investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized trial to evaluate the effects of finerenone on vascular stiffness and cardiorenal biomarkers in type 2 diabetes and chronic kidney disease (FIVE-STAR).

BACKGROUND: The overactivation of mineralocorticoid receptor (MR) plays a key pathological role in the progression of cardiovascular and renal diseases by promoting pro-inflammatory and pro-fibrotic signaling. Recently, it has been found that finerenone, a novel nonsteroidal selective MR antagonist, can robustly improve cardiorenal outcomes in patients with type 2 diabetes (T2D) and a wide spectrum of chronic kidney disease (CKD). However, the mechanisms underlying the cardiorenal benefits of finerenone are poorly understood. Further, whether the clinical benefits are mediated by an improvement in vascular stiffness is not confirmed. Therefore, the current study aims to evaluate the effects of finerenone on vascular stiffness as assessed using cardio ankle vascular index (CAVI) and relevant cardiorenal biomarkers in patients with T2D and CKD. METHODS: The Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in Type 2 Diabetes and Chronic Kidney Disease (FIVE-STAR) is an ongoing, investigator-initiated, multicenter, prospective, placebo-controlled, double-blind, randomized clinical trial in Japan. Its target sample size is 100 subjects. Recruitment will be performed from September 2023 to July 2024. After obtaining informed consent, eligible participants with T2D and CKD (25 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 90 mL/min/1.73 m2 and 30 mg/g Cr ≤ urinary albumin-to-creatinine ratio [UACR] < 3500 mg/g Cr) will be equally randomized to receive 24-week treatment with either finerenone (starting dose at 10 mg once daily in participants with a baseline eGFR < 60 mL/min/1.73 m2 or at 20 mg once daily in those with a baseline eGFR ≥ 60 mL/min/1.73 m2) or dose-matched placebo. The primary endpoint is the change from baseline in CAVI at 24 weeks. The secondary endpoints are changes from baseline in UACR at 12 and 24 weeks and relevant serum and urinary biomarkers at 24 weeks. As an exploratory endpoint, proteomic analysis using the Olink® Target 96 panels will be also performed. DISCUSSION: FIVE-STAR is the first trial evaluating the therapeutic impact of finerenone on vascular stiffness and relevant cardiorenal biomarkers in patients with T2D and CKD. This study will provide mechanistic insights on the clinical benefits of finerenone based on recent cardiovascular and renal outcome trials. Trial registration Unique Trial Number, NCT05887817 ( https://clinicaltrials.gov/ct2/show/NCT05887817 ) and jRCTs021230011 ( https://jrct.niph.go.jp/latest-detail/jRCTs021230011 ).

Larissa Heart Failure Risk Score and Mode of Death in Acute Heart Failure: Insights from REALITY-AHF.

Patients with heart failure (HF) patients may die either suddenly (sudden cardiac death/SCD) or progressively from pump failure. The heightened risk of SCD in patients with HF may expedite important decisions about medications or devices. We used the Larissa Heart Failure Risk Score (LHFRS), a validated risk model for all-cause mortality and HF rehospitalization, to investigate the mode of death in 1363 patients enrolled in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF). Cumulative incidence curves were generated using a Fine-Gray competing risk regression, with deaths that were not due to the cause of death of interest as a competing risk. Likewise, the Fine-Gray competing risk regression analysis was used to evaluate the association between each variable and the incidence of each cause of death. The AHEAD score, a well-validated HF risk score ranging from 0 to 5 (atrial fibrillation, anemia, age, renal dysfunction, and diabetes mellitus), was used for the risk adjustment. Patients with LHFRS 2-4 exhibited a significantly higher risk of SCD (HR hazard ratio adjusted for AHEAD score 3.15, 95% confidence interval (CI) (1.30-7.65), p = 0.011) and HF death (adjusted HR for AHEAD score 1.48, 95% CI (1.04-2.09), p = 0.03), compared to those with LHFRS 0,1. Regarding cardiovascular death, patients with higher LHFRS had significantly increased risk compared to those with lower LHFRS (HR 1.44 adjusted for AHEAD score, 95% CI (1.09-1.91), p = 0.01). Lastly, patients with higher LHFRS exhibited a similar risk of non-cardiovascular death compared to those with lower LHFRS (HR 1.44 adjusted for AHEAD score, 95% CI (0.95-2.19), p = 0.087). In conclusion, LHFRS was associated independently with the mode of death in a prospective cohort of hospitalized HF patients.

Efficacy and Safety of Home-Based Cardiac Telemonitoring Rehabilitation in Patients After Transcatheter Aortic Valve Implantation: Single-Center Usability and Feasibility Study.

BACKGROUND: No consensus exists on the efficacy of home-based cardiac rehabilitation (CR) in patients who have undergone transcatheter aortic valve implantation (TAVI). Additionally, there are no reports on home-based cardiac telemonitoring rehabilitation (HBTR) in patients after TAVI. OBJECTIVE: We aimed to investigate the efficacy of HBTR in patients who have undergone TAVI. METHODS: This single-center preliminary study introduced HBTR to patients after TAVI, and the efficacy outcomes of the rehabilitation method were compared to that of a historical control cohort. The historical control cohort (control group) consisted of 6 consecutive patients who underwent ordinary outpatient CR after TAVI from February 2016 to March 2020. Patients who participated in the HBTR program were only recruited after the TAVI procedure and before discharge between April 2021 and May 2022. In the first 2 weeks after TAVI, patients underwent outpatient CR and were trained using telemonitoring rehabilitation systems. Thereafter, patients underwent HBTR twice a week for 12 weeks. The control group performed standard outpatient CR at least once a week for 12 to 16 weeks. Efficacy was assessed using peak oxygen uptake (VO2) prior to and after CR. RESULTS: Eleven patients were included in the HBTR group. All patients underwent 24 HBTR sessions during the 12-week training period, and no adverse events were observed. The control group participants performed 19 (SD 7) sessions during the training period, and no adverse events were observed. Participants in the HBTR and control groups had a mean age of 80.4 (SD 6.0) years and 79.0 (SD 3.9) years, respectively. In the HBTR group, preintervention and postintervention peak VO2 values were 12.0 (SD 1.7) mL/min/kg and 14.3 (SD 2.7) mL/min/kg (P=.03), respectively. The peak VO2 changes in the HBTR and control groups were 2.4 (SD 1.4) mL/min/kg and 1.3 (SD 5.0) mL/min/kg (P=.64), respectively. CONCLUSIONS: Home-based CR using a telemonitoring system is a safe outpatient rehabilitation method. Its efficacy is not inferior to that of standard CR in patients who have undergone TAVI. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs032200122; https://jrct.niph.go.jp/latest-detail/jRCTs032200122.

Rationale and Design of the Effect of Ivabradine on Exercise Tolerance in Patients With Chronic Heart Failure (EXCILE-HF) Trial　- Protocol for a Multicenter Randomized Controlled Trial.

Background: A high resting heart rate is an independent risk factor for mortality and morbidity in patients with cardiovascular diseases. Ivabradine selectively inhibits the funny current (I f) and decreases heart rate without affecting cardiac conduction, contractility, or blood pressure. The effect of ivabradine on exercise tolerance in patients with heart failure with reduced ejection fraction (HFrEF) on standard drug therapies remains unclear. Methods and Results: This multicenter interventional trial of patients with HFrEF and a resting heart rate ≥75 beats/min in sinus rhythm treated with standard drug therapies will consist of 2 periods: a 12-week open-label, randomized, parallel-group intervention period (standard drug treatment+ivabradine group and standard drug treatment group) to compare changes in exercise tolerance between the 2 groups; and a 12-week open-label ivabradine treatment period for all patients to evaluate the effect of adding ivabradine on exercise tolerance. The primary endpoint will be the change in peak oxygen uptake (V̇O2) during the cardiopulmonary exercise test from Week 0 (baseline) to Week 12. Secondary endpoints will be time-dependent changes in peak V̇O2 from Week 0 to Weeks 12 and 24. Adverse events will also be evaluated. Conclusions: The EXCILE-HF trial will provide meaningful information regarding the effects of ivabradine on exercise tolerance in patients with HFrEF receiving standard drug therapies and suggestions for the initiation of ivabradine treatment.

Derivation and validation of a machine learning-based risk prediction model in patients with acute heart failure.

BACKGROUND: Risk stratification is important in patients with acute heart failure (AHF), and a simple risk score that accurately predicts mortality is needed. The aim of this study is to develop a user-friendly risk-prediction model using a machine-learning method. METHODS: A machine-learning-based risk model using least absolute shrinkage and selection operator (LASSO) regression was developed by identifying predictors of in-hospital mortality in the derivation cohort (REALITY-AHF), and its performance was externally validated in the validation cohort (NARA-HF) and compared with two pre-existing risk models: the Get With The Guidelines risk score incorporating brain natriuretic peptide and hypochloremia (GWTG-BNP-Cl-RS) and the acute decompensated heart failure national registry risk (ADHERE). RESULTS: In-hospital deaths in the derivation and validation cohorts were 76 (5.1 %) and 61 (4.9 %), respectively. The risk score comprised four variables (systolic blood pressure, blood urea nitrogen, serum chloride, and C-reactive protein) and was developed according to the results of the LASSO regression weighting the coefficient for selected variables using a logistic regression model (4 V-RS). Even though 4 V-RS comprised fewer variables, in the validation cohort, it showed a higher area under the receiver operating characteristic curve (AUC) than the ADHERE risk model (AUC, 0.783 vs. 0.740; p = 0.059) and a significant improvement in net reclassification (0.359; 95 % CI, 0.10-0.67; p = 0.006). 4 V-RS performed similarly to GWTG-BNP-Cl-RS in terms of discrimination (AUC, 0.783 vs. 0.759; p = 0.426) and net reclassification (0.176; 95 % CI, -0.08-0.43; p = 0.178). CONCLUSIONS: The 4 V-RS model comprising only four readily available data points at the time of admission performed similarly to the more complex pre-existing risk model in patients with AHF.

Cardiac Rehabilitation for Patients With Stable Ischemic Heart Disease Without Revascularization　- Rationale and Design of a Single-Arm Pilot Study.

Background: Clinical practice guidelines strongly recommend optimal medical therapy (OMT), including lifestyle modification, pharmacotherapy, and exercise-based cardiac rehabilitation (CR), in patients with stable ischemic heart disease (SIHD). However, the efficacy and safety of CR in patients with SIHD without revascularization remain unclear. Methods and Results: The Prospective Registry of STable Angina RehabiliTation (Pre-START) study is a multicenter, prospective, single-arm, open-label pilot study to evaluate the efficacy and safety of CR on health-related quality of life (HRQL), exercise capacity, and clinical outcomes in Japanese patients with SIHD without revascularization. In this study, all patients will undergo guideline-based OMT and are encouraged to have 36 outpatient CR sessions within 5 months after enrollment. The primary endpoint is the change in the Seattle Angina Questionnaire-7 summary score between baseline and the 6-month visit; an improvement of ≥5 points will be defined as a clinically important change. Secondary endpoints include changes in other HRQL scores and exercise capacity between baseline and the 6-month visit, as well as clinical outcomes between enrollment and the 6-month visit. Conclusions: The Pre-START study will provide valuable evidence to elucidate the efficacy and safety of CR in patients with SIHD and indispensable information for a subsequent randomized controlled trial. The study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (ID: UMIN000045415) on April 1, 2022.

Nutritional management of heart failure.

Nutrition in the cardiovascular field to date has focused on improving lifestyle-related diseases such as hypertension and diabetes from the viewpoint of secondary prevention. For these conditions, "nutrition for weight loss" is recommended, and nutritional guidance that restricts calories is provided. On the other hand, in symptomatic Stage C and D heart failure, it is known that underweight patients who manifest poor nutrition, sarcopenia, and cardiac cachexia have a poor prognosis. This is referred to as the "Obesity paradox". In order to "avoid weight loss" in patients with heart failure, a paradigm shift to nutritional management to prevent weight loss is needed. Rather than prescribing uniform recommendation for salt reduction of 6 g/day or less, awareness of the behavior change stage model is attracting attention. In this setting, the value of salt restriction will need to be determined to determine the priority level of intervention for undernutrition versus the need to prevent congestive signs and symptoms. In the Intensive Care Unit (ICU)/Cardiac Care Unit (CCU) for acute heart failure, nutritional intervention should be considered within 48 h of admission. Key points are selection of access route, timing of intervention, and monitoring of side effects. In nutritional management at home and in end-of-life care, food is a reflection of an individual's values, as well as a source of joy and encouragement. The importance of digestive tract should also be recognized in heart failure from oral flail to intestinal edema, constipation, and the intestinal bacteria called the heart-gut axis. Finally, we would like to propose a new term "heart nutrition" for nutritional management in patients with heart failure in this review. Compared to the evidence for exercise therapy in heart failure, studies assessing nutritional management remain scarce and there is a need for research in this area in the future.

Canagliflozin independently reduced plasma volume from conventional diuretics in patients with type 2 diabetes and chronic heart failure: a subanalysis of the CANDLE trial.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of heart failure progression and mortality rates. Moreover, osmotic diuresis induced by SGLT2 inhibition may result in an improved heart failure prognosis. Independent of conventional diuretics in patients with type 2 diabetes (T2D) and chronic heart failure, especially in patients with heart failure with preserved ejection fraction (HFpEF), it is unclear whether SGLT2i chronically reduces estimated plasma volume (ePV). As a subanalysis of the CANDLE trial, which assessed the effect of canagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP), we examined the change (%) in ePV over 24 weeks of treatment based on the baseline level associated with diuretic usage. In the CANDLE trial, nearly all patients were clinically stable (NYHA class I-II), with approximately 70% of participants presenting a baseline phenotype of HFpEF. A total of 99 (42.5%) patients were taking diuretics (mostly furosemide) at baseline, while 134 (57.5%) were not. Relative to glimepiride, canagliflozin significantly reduced ePV without worsening renal function in patients in both groups: -4.00% vs. 1.46% (p = 0.020) for the diuretic group and -6.14% vs. 1.28% (p < 0.001) for the nondiuretic group. Furthermore, canagliflozin significantly reduced serum uric acid without causing major electrolyte abnormalities in patients in both subgroups. The long-term beneficial effect of SGLT2i on intravascular congestion could be independent of conventional diuretic therapy without worsening renal function in patients with T2D and HF (HFpEF predominantly). In addition, the beneficial effects of canagliflozin are accompanied by improved hyperuricemia without causing major electrolyte abnormalities.

Hospital-acquired disability in older heart failure patients decreases independence and increases difficulties in activities of daily living.

AIMS: The aim of this study was to clarify whether worsening of independence in activities of daily living (ADL) and also difficulties in ADL are triggered by hospitalization in older patients with heart failure (HF) and whether difficulties in ADL can predict readmission for HF regardless of independence in ADL in these patients. METHODS AND RESULTS: We enrolled 241 HF patients in the present multi-institutional, prospective, observational study. The patients were divided according to age into the non-older patient group (<75 years, n = 137) and the older patient group (≥75 years, n = 104). The Katz index and the Performance Measure for Activities of Daily Living-8 (PMADL-8) were used to evaluate independence and difficulties in ADL, respectively. The endpoint of this study was rehospitalization for HF. Independence as indicated by the Katz index at discharge was significantly lower than that before admission only in the older patient group, and the value of the PMADL-8 at discharge was significantly higher than that before admission (P < 0.001). In all patients, after adjusting for the Katz index and other variables, PMADL-8 score was a significant predictor of rehospitalization for HF (hazard ratio 1.50; 95% confidence interval 1.07-2.13; P = 0.021). CONCLUSIONS: Worsening of both independence and difficulties in ADL was triggered by hospitalization in older HF patients, and difficulties in ADL were relevant factors for risk of rehospitalization regardless of independence in ADL. These findings indicate the importance of preventing not only decreased independence but also increased difficulties in ADL during and after hospitalization.