Japanese Heart Failure Patients Research Articles

The prognostic impact of renal dysfunction and anemia in japanese heart failure patients stratified by left ventricular ejection fraction

Abstract Background Renal dysfunction and anemia have been reported to be important prognostic factors in heart failure (HF) patients, but the differences in their effects stratified by left ventricular ejection fraction (LVEF) are not clear. Therefore, we investigated the prognostic impact of renal dysfunction and anemia in Japanese HF patients stratified by LVEF. Methods We combined two registry studies of acute HF patients in Japan and examined major events and associated factors during 2-year observation period. The primary endpoint was defined as all-cause mortality or HF hospitalization. Renal dysfunction was defined as eGFR <60 mL/min/1.73 m2, and anemia was defined as hemoglobin <13 g/dl in men and 12 g/dl in women. Two groups were also analyzed by LVEF (LVEF >50% and LVEF <49%). Results A total of 2142 patients were enrolled and analyzed. The mean observation period was 623±244 days. Mean age was 78.7 years. Forty-nine percent were male. Coronary artery disease and atrial fibrillation were present in 31% and 44% of patients, respectively. Medications included beta-blockers in 61% of patients and RAS inhibitors in 53%. Renal dysfunction was present in 1676 patients (74%) and anemia in 1523 patients (67%). Combination of both was observed in 1190 patients (53%). The primary endpoint was observed in 1015 patients, with 563 deaths and 737 HF hospitalizations. Multivariate analysis in a Cox proportional hazards model showed that renal dysfunction alone (HR: 1.39, 95%CI:1.06-1.81, p=0.02) and combination of renal dysfunction and anemia (HR 1.72, 95%CI:1.34-2.21, p<0.01) were independent prognostic factors in all patients. In patients with LVEF <49%, renal dysfunction alone (HR: 1.50, 95%CI:1.04-2.16, p=0.03) and combination of renal dysfunction and anemia (HR: 1.90, 95%CI:1.34-2.68, p<0.01) were predictive factors. On the other hand, in patients with LVEF >50%, only the combination of renal dysfunction and anemia were independent predictors (HR: 1.46, 95%CI:1.01-2.10, p=0.04). Conclusion We identified differences in the prognostic impact of anemia and renal dysfunction by LVEF.

Influenza Vaccination and Cardiovascular Events in Japanese Patients With Heart Failure - Findings From the PARALLEL-HF Trial.

Influenza is associated with an increased risk for cardiovascular events in patients with heart failure (HF). This study aimed to investigate the prevalence of influenza vaccination among Japanese patients with HF enrolled in the PARALLEL-HF (Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) trial and the association between receiving influenza vaccination and cardiovascular events including death or HF hospitalization. In PARALLEL-HF, in which 223 patients with HF and reduced ejection fraction (HFrEF) were randomized to the angiotensin-receptor neprilysin inhibitor (sacubitril/valsartan) or enalapril, 97 (43%) received influenza vaccination. Influenza vaccination tended to be associated, though statistically not significant, with a lower risk for all-cause death (adjusted hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.32-1.39) and cardiopulmonary or influenza-related hospitalization or death (adjusted HR: 0.72; 95% CI: 0.46-1.11) in propensity score-adjusted models. The influenza vaccination rate in Japanese patients with HFrEF who were well managed on guideline-directed medical therapy was suboptimal despite recommendations from clinical practice guidelines. However, importantly, it could be associated with better clinical benefits.

Multicenter prospective observational study to clarify the current status and clinical outcome in Japanese patients who have an indication for implantable cardioverter defibrillator (ICD) or wearable cardioverter defibrillator (WCD) (TRANSITION JAPAN‐ICD/WCD study): Rationale and design of a prospective, multicenter, observational, comparative study

AbstractBackgroundDespite the positive impact of implantable cardioverter defibrillators (ICDs) and wearable cardioverter defibrillators (WCDs) on prognosis, their implantation is often withheld especially in Japanese heart failure patients with reduced left ventricular ejection fraction (HFrEF) who have not experienced ventricular tachycardia (VT) or ventricular fibrillation (VF) for uncertain reasons. Recent advancements in heart failure (HF) medications have significantly improved the prognosis for HFrEF. Given this context, a critical reassessment of the treatment and prognosis of ICDs and WCDs is essential, as it has the potential to reshape awareness and treatment strategies for these patients.MethodsWe are initiating a prospective multicenter observational study for HFrEF patients eligible for ICD in primary and secondary prevention, and WCD, regardless of device use, including all consenting patients. Study subjects are to be enrolled from 31 participant hospitals located throughout Japan from April 1, 2023, to December 31, 2024, and each will be followed up for 1 year or more. The planned sample size is 651 cases. The primary endpoint is the rate of cardiac implantable electronic device implementation. Other endpoints include the incidence of VT/VF and sudden death, all‐cause mortality, and HF hospitalization, other events. We will collect clinical background information plus each patient's symptoms, Clinical Frailty Scale score, laboratory test results, echocardiographic and electrocardiographic parameters, and serial changes will also be secondary endpoints.ResultsNot applicable.ConclusionThis study offers invaluable insights into understanding the role of ICD/WCD in Japanese HF patients in the new era of HF medication.

Independent Link Between Use of Mineralocorticoid Receptor Antagonists and Muscle Wasting in Heart Failure Patients Not Receiving Renin-Angiotensin System Inhibitors.

The renin-angiotensin system (RAS) activation is a proposed mechanism of muscle wasting (MW i.e., reduction in muscle mass). Although we reported that RAS inhibitors (RASIs) were associated with lower prevalence of MW in heart failure (HF) patients, the relationship between mineralocorticoid receptor (MR) signaling and MW has not been analyzed. We analyzed data from 320 consecutive Japanese HF patients who underwent dual-energy X-ray absorptiometry scanning for assessment of appendicular skeletal muscle mass index (ASMI). In multiple linear regression analyses, plasma renin activity (PRA) was negatively correlated with ASMI in patients not receiving RASIs, indicating an untoward role of the RAS in MW. Results of analysis of covariance in which risk factors of MW served as covariates showed that use of MR antagonists (MRAs) was associated with lower ASMI and higher PRA in the non-RASIs group. The close relationship between use of MRAs and lower ASMI or higher PRA in the non-RASIs group was confirmed in analyses in which the differences in baseline characteristics between users and non-users of MRAs were minimized by using an inverse probability of treatment weighting. Increased PRA by MR inhibition without concurrent RAS inhibition, possibly contributing to upregulation of angiotensin II signaling, may be associated with reduction in muscle mass.

Abstract 13743: Validity and Reliability of a Palliative Care Needs Assessment Tool in Japanese Patients With Heart Failure

Backgrounds: Although patients with heart failure (HF) frequently experience considerable symptom burden and require significant care similar to those with cancer, most HF patients do not receive timely intervention due to the absence of standardized method for identifying those in need of palliative care. Several tools have been employed to assess palliative care needs and identify eligible patients. However, their validity and reliability have yet to be fully examined worldwide. We sought to assess the validity and reliability of The Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF) in Japanese HF population. Methods: We enrolled consecutive HF patients admitted in our university hospital between February and May 2023 and their caregivers were also included. The NAT: PD-HF were translated into Japanese by our professional multidisciplinary team in accordance with cultural and medical background. We assessed the internal consistency of the NAT: PD-HF with Cronbach`s alpha, and the inter-rater and test-retest reliability with Cohen`s kappa. After using this tool, patients, caregivers, and health care providers were asked whether the tool adequately identify their burden and care needs. Results: During the study period, 75 patients, 67 caregivers, and 17 health care providers agreed to participate. Cronbach's alpha was 0.80 and the minimum Kappa coefficient was 0.73 for inter-rater reliability and 0.83 for test-retest reliability. Seventy-one patients (94%) and 64 caregivers (95%) found this tool useful to identify their burden and care needs. Seventy patients (93%) and 63 caregivers (94%) felt that the tool will improve the quality of care. Sixteen health care providers (94%) also believed this tool was helpful to understand the burden and care needs of both patients and caregivers. However, 7 of them (41%) considered they may not have enough time to use the tool in their daily clinical practice. Conclusions: The NAT: PD-HF was suggested to be a reliable and potentially valid tool even among Japanese HF patients. This tool was very well accepted by patients, caregivers, and health care providers to identify burden and care needs. Further follow-up studies are needed to examine the prognostic impact of using this tool.

Psychometric properties of the Japanese version of the Self-Care of Heart Failure Index version 7.2.

It is more important for patients with heart failure (HF) to objectively identify their self-care status. The Self-Care of Heart Failure Index (SCHFI) version 7.2 is a reliable and valid instrument comprising three scales: self-care maintenance, symptom perception, and self-care management. We aimed to translate the SCHFI v.7.2 into Japanese and test its validity and reliability. This was a cross-sectional study. Two translators performed forward and backward translations between English and Japanese. To assess structural validity, confirmatory factor analyses were performed using the structure of the original version. To assess convergent validity, the associations between each scale and self-care self-efficacy were evaluated. To assess internal consistency, model-based internal consistency coefficients were calculated. Participants were 314 Japanese outpatients with HF (mean age: 72.8 ± 12.8 years). Regarding structural validity, all scales showed adequate model fit indices, supporting a two-factor structure with items similar to those in the original version. However, to improve the model fit indices, it was necessary to add error correlations for the self-care maintenance and symptom perception scales. Regarding convergent validity, all scales showed significant associations with self-care self-efficacy. Regarding internal consistency, the model-based internal consistency coefficients were sufficient for all scales (0.739, 0.908, and 0.783 for the self-care maintenance, symptom perception, and self-care management scales, respectively). The Japanese version of the SCHFI v.7.2 had adequate validity and reliability. This instrument is useful for assessing self-care in Japanese HF patients. However, factors influencing self-care should be considered when interpreting results.

Stereoselective interaction of tolvaptan with amiodarone under racemic metabolic impact by CYP3A5 genotypes in heart failure patients.

The diuretic effect of tolvaptan is largely blood level-dependent although it does exhibit interindividual differences according to cytochrome P450 (CYP) 3A5 genotype. This study aimed to investigate the pharmacokinetic relationship between plasma tolvaptan and its monohydroxylate enantiomers and the factors affecting their metabolism in heart failure patients. Japanese heart failure patients (n = 88) receiving oral tolvaptan (median dosage 7.5mg/day) were enrolled. Blood samples were collected prior to the dosing on day 6 or later after first administration to determine the plasma concentrations of tolvaptan and its monohydroxylate enantiomers. Gene polymorphisms of CYP3A5, carbonyl reductase (CBR) 1/3, and ATP-binding cassette subfamily B member (ABCB) 1 were analyzed for their impact on tolvaptan pharmacokinetics. Serum laboratory test values and concomitant use of amiodarone were evaluated as factors related to tolvaptan metabolism. The median of the sum of the 5S- and 5R-tolvaptan plasma concentrations was 48.9 (range, 15.3-100) ng/mL. CYP3A5 genotypes significantly affected the concentration ratio of all enantiomeric metabolites to tolvaptan, while the other metabolic-related gene polymorphisms had no influence. A negative correlation was found between serum albumin and the enantiomeric ratio of tolvaptan and monohydroxylate DM-4111. Concomitant use of amiodarone increased the plasma levels of whole tolvaptan but significantly decreased the metabolic ratios of 5R-tolvaptan. 5S-tolvaptan was selectively synthesized from ketone MOP-21826 by CBR1 with a substantially smaller reaction velocity compared to tolvaptan monohydroxylation by CYP3A4/5. This study clarified the racemic impact of CYP3A5 genotypes on tolvaptan metabolism. Amiodarone may stereoselectively interact with R-forms rather than S-forms of tolvaptan.

Abstract 11945: A Paradox of Medical Cost and Outcomes: A Comparison of Acute Heart Failure Outcomes in the United States vs. Japan

Background: Despite advances in therapy, the burden of heart failure (HF) has not declined in the US. Comparing HF between nations may provide hypothesis generating research to improve outcomes and decrease costs. We directly compared characteristics, management, cost, and outcomes of acute HF hospitalization in the US vs. Japan. Methods: We identified acute HF patients (age >65) in US Medicare Part A, B, and D data and Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter registry in 2013. We described patient characteristics, length of stay (LOS), cost paid, post-discharge follow-up (f/u), CV medications, death, and CV readmission. Results: We identified 11,193 Japanese and 120,289 US patients hospitalized for acute HF. While similar in age and gender, US patients were more likely to have multiple comorbidities (Table). Japanese patients had a 3-fold longer median LOS, a 3-fold lower median per-day hospital cost paid, more than 10-fold likely to receive cardiac rehab, and were more likely to receive CV medications. While inpatient mortality was higher in Japan (8.6% vs 3.2%), overall mortality after HF admission and CV readmission was 1.5-2-fold higher in US patients (Figure). US patients had higher physician f/u within 14 days but overall f/u rate was higher in Japan. Conclusion: Despite longer LOS with lower hospital costs, Japanese HF patients had high inpatient cardiac rehab participation, more CV medications, higher f/u rate with a physician, and better survival. Further studies may assess potential interventions (e.g. inpatient cardiac rehab, prevention of premature discharge) to improve outcomes in US HF patients.

Abstract 10892: Cross-Cultural Validation and Psychometric Testing of the Heart Failure Somatic Perception Scale in Japan

Background: The assessment of symptoms experienced by patients with heart failure (HF) has important contextual implications for self-care and allows for early recognition of signs of worsening HF. The Heart Failure Somatic Perception Scale (HFSPS) is a measurement tool developed in the U.S. to assess symptoms experienced by patients with HF, but it is expected to be applicable to patients in countries with different cultural backgrounds. Objectives: To evaluate the psychometric properties (validity and reliability) of the HFSPS in Japanese HF patients. Methods: This study assessed the factor structure of the HFSPS using confirmatory factor analysis in 320 HF outpatients in Japan. Criterion-related validity of the HFSPS was evaluated by correlating its factor scores with Patient-Reported Outcomes Measurement Information System (PROMIS) scores using Pearson's correlation coefficient. Internal consistency reliability of the HFSPS was evaluated using the factor score coefficient of determination, Cronbach's alpha, and the model-based internal consistency index. Results: The sample (n=320) was 72% male, mean age 72.9±12.8 years. Confirmatory factor analysis examining the four-factor structure of the HFSPS (dyspnea, chest discomfort, early and subtle, and edema), resulted in resulted in the following fit indices: χ2= (129, N=310), P<0.001, comparative fit index =0.825, Tucker-Lewis index =0.793, root mean square error of approximation =0.131. For criterion-related validity, all domains of the PROMIS items (physical health, mental health, global health, and social role satisfaction) were negatively correlated (-0.07 to -0.37) and statistically significant indicating higher symptom burden was associated with worse global health. HFSPS reliability resulted in Cronbach's alpha 0.878 for dyspnea, 0.607 for chest discomfort, 0.772 for early and subtle, 0.777 for edema, and 0.921 for the entire scale. Conclusion: This study suggests the HFSPS is a reliable and valid tool among Japanese with HF. Using this scale will provide accurate assessment of symptoms experienced by HF patients in research testing educational interventions to improve HF symptom recognition and response.

Initial Real-World Practical Experience of Sacubitril/Valsartan Treatment in Japanese Patients With Chronic Heart Failure.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has demonstrated survival benefit and reduces heart failure hospitalization compared with enalapril in patients with heart failure and reduced ejection fraction. However, its efficacy in real-world practice in Japan remains unknown.Methods and Results: We initiated sacubitril/valsartan treatment for 37 patients (median age 68 years; median left ventricular ejection fraction 37%) between August and November 2020. Within 3 months, sacubitril/valsartan was discontinued in 3 patients due to symptomatic hypotension or worsening heart failure. Two patients were hospitalized due to worsening heart failure, with one of these patients undergoing percutaneous mitral valve repair. Three patients received scheduled non-pharmacological treatment: 1 received cardiac resynchronization therapy (CRT), 1 received CRT and underwent transcatheter aortic valve implantation, and 1 underwent left ventricular assist device implantation. Of the 30 patients who continued sacubitril/valsartan for 3–6 months without additional non-pharmacological therapy, there was a tendency for a decrease in N-terminal pro B-type natriuretic peptide concentrations (baseline vs. after 3–6 months ARNI treatment; median 733 vs. 596 pg/mL; P=0.097) and an increase in left ventricular ejection fraction (median 37% vs. 39%; P=0097).Conclusions: Sacubitril/valsartan therapy with a lower initial dose was safe and may be effective in Japanese heart failure patients in a real-world setting. Further evaluation of optimal patient selection and clinical management using sacubitril/valsartan is warranted.

Rationale and design of the HINODE study: Heart failure indication and sudden cardiac death prevention trial Japan.

BackgroundRandomized trials in Western countries have provided evidence that prophylactic implantable cardioverter‐defibrillator (ICD) therapy reduces mortality in heart failure (HF) patients with reduced left ventricular ejection fraction. However, the risk of life‐threatening ventricular arrhythmias in Japanese HF patients sharing similar risk factors is still unknown.MethodsThe Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan trial (NCT03185832) is a prospective, multicenter registry designed to collect data on ventricular arrhythmia, HF events, and mortality in Japanese HF patients. Japanese patients with HF and 2‐5 predefined risk factors who were indicated for cardiac device implantation based on European Society of Cardiology guidelines were enrolled in four treatment arms: implantable cardioverter‐defibrillator (ICD), cardiac resynchronization therapy defibrillator (CRT‐D), HF pacing (PA; Pacemaker and cardiac resynchronization pacemaker), and nondevice (ND) cohorts and followed for a minimum of 12 months. Since it is anticipated that some baseline patient characteristics and risk factors will differ significantly from those reported in predominantly Western populations, event rates will be compared to a propensity‐matched population from the MADIT RIT trial. Primary endpoints are composite rates of first appropriately treated ventricular arrhythmias (VA) or/and life‐threatening VA symptoms for the ICD and CRT‐D cohorts. For nondevice and PA cohorts, the primary outcome is all‐cause mortality.ConclusionsThe Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan is a large prospective multicenter registry with defined device treatment cohorts and will provide data for risk stratification for cardiovascular events in Japanese HF patients.

Efficacy and Safety of Sacubitril/Valsartan in Japanese Patients With Chronic Heart Failure and Reduced Ejection Fraction - Results From the PARALLEL-HF Study.

In the Prospective Comparison of angiotensin receptor neprilysin inhibitor (ARNI) With ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study, treatment with sacubitril/valsartan reduced the primary outcome of cardiovascular (CV) death and heart failure (HF) hospitalization compared with enalapril in patients with chronic HF and reduced ejection fraction (HFrEF). A prospective randomized trial was conducted to assess the efficacy and safety of sacubitril/valsartan in Japanese HFrEF patients. In the Prospective comparison of ARNI with ACEi to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients (PARALLEL-HF) study, 225 Japanese HFrEF patients (New York Heart Association [NYHA] class II-IV, left ventricular ejection fraction [LVEF] ≤35%) were randomized (1 : 1) to receive sacubitril/valsartan 200 mg bid or enalapril 10 mg bid. Over a median follow up of 33.9 months, no significant between-group difference was observed for the primary composite outcome of CV death and HF hospitalization (HR 1.09; 95% CI 0.65-1.82; P=0.6260). Early and sustained reductions in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline were observed with sacubitril/valsartan compared with enalapril (between-group difference: Week 2: 25.7%, P<0.01; Month 6: 18.9%, P=0.01, favoring sacubitril/valsartan). There was no significant difference in the changes in NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score at Week 8 and Month 6. Sacubitril/valsartan was well tolerated with fewer study drug discontinuations due to adverse events, although the sacubitril/valsartan group had a higher proportion of patients with hypotension. In Japanese patients with HFrEF, there was no difference in reduction in the risk of CV death or HF hospitalization between sacubitril/valsartan and enalapril, and sacubitril/valsartan was safe and well tolerated.

Overestimation of glomerular filtration rate by creatinine-based equation in heart failure patients is predicted by a novel scoring system.

Creatinine-based estimated glomerular filtration rate (eGFRcre) has been shown to overestimate the glomerular filtration rate (GFR) when it is compared with cystatin C-based estimated GFR (eGFRcys) in older people. We investigated clinical determinants of GFR overestimation by eGFRcre and developed a score for prediction of GFR overestimation (OE) in heart failure patients. We retrospectively examined 244 Japanese heart failure patients (aged 72.2 ± 13.1 years; 48% women) who had no known extrarenal factors that affect serum cystatin C concentration. eGFR OE by eGFRcre was defined as eGFRcre being ≥120% of cystatin C-based eGFR. The proportion of heart failure patients with OE was 14.3%. Patients with OE were older, had lower body weight and total skeletal muscle mass than those in patients without OE. Laboratory examinations showed that hemoglobin concentration was lower, and the ratio of blood urea nitrogen-to-creatinine was higher in patients with OE than in patients without OE. In multivariate regression analysis, body weight (<63.0 kg in men and <42.0 kg in women), hemoglobin level (<12.4 g/dL in men and <11.0 g/dL in women) and ratio of blood urea nitrogen-to-creatinine (>26.5) in addition to skeletal muscle mass were independently associated with OE. A score calculated by using cut-off levels of body weight, hemoglobin concentration and ratio of blood urea nitrogen-to-creatinine predicted OE with a sensitivity of 97.1% and a specificity of 98.1%. Overestimation of GFR by eGFRcre is predictable by a novel scoring system, which might be useful for the detection of patients who require cystatin C-based eGFR measurement for accurate assessment of renal function. Geriatr Gerontol Int 2020; 20: 752-758.

Changes in characteristics and outcomes in Japanese patients with heart failure from the 2000s to the 2010s: The HIJ-HF cohorts

BackgroundThe number of hospitalized patients with heart failure (HF) is increasing as a result of the increase in the elderly population in Japan. We evaluated changes in the characteristics and outcomes of HF patients hospitalized in the 2000s to the 2010s and discharged alive based on left ventricular ejection fraction (LVEF). MethodsPooled patient data were obtained from The Heart Institute of Japan Heart Failure studies (HIJ-HF I: 2001-2 and HIJ-HF II: 2013–4). We studied patients discharged alive from pooled data based on LVEF < 40% (HFrEF), 40–49% (HFmrEF), and ≥50% (HFpEF). The primary outcome was death from any cause, and the secondary outcomes were cardiac death and rehospitalization due to worsened HF. ResultsThe proportion of HFpEF increased (35%–43%, p < 0.01), and the median ages of patients with HFmrEF (72–76 years, p < 0.01) or HFpEF (72–80 years, p < 0.01) increased from HIJ-HF I to HIJ-HF II. The use of angiotensin II receptor blockers, beta-blockers, statins, amiodarone, and erythropoietin increased, but nitrate and digoxin usage decreased. The adjusted survival rate and cardiac death-free rate were not significantly different between the 2000s and 2010s in any LVEF group, and the incidence of rehospitalization due to worsened HF was reduced in patients discharged alive from HIJ-HF I to HIJ-HF II [HFrEF: hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.51–0.89; HFmrEF: HR 0.89, 95% CI 0.68–1.16; and HFpEF: HR 0.77, 95% CI 0.61–0.97] with no significant interaction by LVEF groups. ConclusionOur study demonstrated that age, the proportion of HFpEF, and guideline-recommended drug therapy use increased among hospitalized Japanese HF patients from the 2000s to the 2010s. The adjusted survival rate was not improved in any LVEF group, although the incidence of rehospitalization due to worsened HF was reduced.

Prediction of sudden cardiac death in Japanese heart failure patients: international validation of the Seattle Proportional Risk Model.

Heart failure (HF) is associated with an increased risk of sudden cardiac death (SCD). This study sought to demonstrate the incidence of SCD within a multicentre Japanese registry of HF patients hospitalized for acute decompensation, and externally validate the Seattle Proportional Risk Model (SPRM). We consecutively registered 2240 acute HF patients from academic institutions in Tokyo, Japan. The discrimination and calibration of the SPRM were assessed by the c-statistic, Hosmer-Lemeshow statistic, and visual plotting among non-survivors. Patient-level SPRM predictions and implantable cardioverter-defibrillator (ICD) benefit [ICD estimated hazard ratio (HR), derived from the Cox proportional hazards model in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)] was calculated. During the 2-year follow-up, 356 deaths (15.9%) occurred, which included 76 adjudicated SCDs (3.4%) and 280 non-SCDs (12.5%). The SPRM showed acceptable discrimination [c-index = 0.63; 95% confidence interval (CI) 0.56-0.70], similar to that of original SPRM-derivation cohort. The calibration plot showed reasonable conformance. Among HF patients with reduced ejection fraction (EF; < 40%), SPRM showed improved discrimination compared with the ICD eligibility criteria (e.g. New York Heart Association functional Class II-III with EF ≤ 35%): c-index = 0.53 (95% CI 0.42-0.63) vs. 0.65 (95% CI 0.55-0.75) for SPRM. Finally, in the subgroup of 246 patients with both EF ≤ 35% and SPRM-predicted risk of ≥ 42.0% (SCD-HeFT defined ICD benefit threshold), mean ICD estimated HR was 0.70 (30% reduction of all-cause mortality by ICD). The cumulative incidence of SCD was 3.4% in Japanese HF registry. The SPRM performed reasonably well in Japanese patients and may aid in improving SCD prediction.

P5649Impact of atrial fibrillation detected by implantable cardioverter-defibrillators on future stroke events in patients with heart failure

Abstract Background Atrial fibrillation (AF) is the most common type of arrhythmia. AF-related stroke tends to be more severe, and the mortality rate is higher compared with stroke without AF. The definition of AF in patients with implanted cardioverter-defibrillators (ICDs) is not clear and the appropriate treatment guideline for patients with AF episode has not established yet. Recent ICDs have led to an improvement in the early detection of AF episodes, especially in patients who are asymptomatic. Previous studies showed that atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices are associated with embolic stroke events. However, little is known about the incidence of AF and stroke events in Japanese heart failure patients with an ICD. Objective The purpose of this study was to identify the incidence of embolic stroke events in heart failure patients with and without AF events detected by ICDs and examine the risk factors of embolic stroke events. Methods We retrospectively analyzed the database of our hospital. Every 6 months, AF events were checked by ICDs. AF30 was defined as AF episodes lasting for ≥30 seconds detected by ICDs. We examined the characteristics and incidence of embolic stroke events and investigated the relationship between AF30 and the incidence of embolic stroke events. Results We enrolled 215 consecutive patients who had no prior AF and took no anticoagulant in this study (follow-up period, 58±35 months; age, 62±15 years; male sex, 75%). The mean CHADS2 score and CHA2DS2-VASc score were 2.4±0.8 points and 3.8±1.2 points, respectively. The mean HAS-BLED score was 2.1±1.0 points. During the follow-up, 14 of 215 patients (6.5%) had embolic stroke events. Nine patients (5.8%/year) and 5 patients (0.65%/year) had embolic stroke events with and without AF30, respectively. The comparison of characteristics among patients with and without embolic stroke events was shown in Table. In multivariate logistic regression analysis, independent predictors for embolic stroke events were new-onset episode of AF30 (odd ratio [OR] 21, 95% confidence interval [CI] 4.8–120, P&lt;0.0001) and an enlarged left atrium ≥40mm (OR 14, 95% CI 2.2–304, P=0.0029). Conclusions Embolic stroke events were common in Japanese heart failure patients with an ICD. AF30 and enlarged left atrium were the risk factors of embolic stroke events in this population. Therefore, when physicians detect new-onset AF in patients with an ICD, they should consider a comprehensive assessment of the risk and benefit of prescribing an anticoagulant.

6131Association between hospital care quality and readmission among Japanese patients with heart failure. From JROAD-DPC study

Abstract Background Measuring the process of care has become a widely used practice to improve a quality of care. Recently, some studies have demonstrated poor to no correlation between 30-day readmission rates and quality of care for heart failure (HF) among hospitalized HF patients. However the investigation about relationships of care quality for HF and 1 year outcome is limited. Purpose To investigate the relationship between quality of care in each hospitals and readmission among HF patients in Japan. Methods From Japanese Registry of All cardiac and vascular diseases (JROAD-DPC) database in 2014, 84,325 HF patients hospitalized to 741 certificated hospitals by Japanese Circulation Society were analyzed. A primary endpoint was readmission for HF in one year. Five performance measures were defined as prescription rate of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), prescription rate of beta blocker and prescription rate of spironolactone, measurement rate of echocardiography and measurement rate of B-type natriuretic peptide (BNP) during hospitalization. For each of the five measures, a composite score was created by giving points ranging from 1 to 4 from the lower quartile of rates, with the score ranging from 5 to 20 points. Hazard ratios (HR) indicating the effects of the performance measures were estimated using Cox proportional hazard models. Covariates included age, gender, Charson score, and NYHA class. Results In Japanese HF patients (age; 78.1 years old, man 52%), the HF readmission rate in one year was 14,520 (17.2%). The readmission rate decreased with higher quartiles of prescription rate in each medications and performance rates. The highest quartile of each measurements was significantly lower risk for readmission compared to the lowest quartile (ACE/ARB, adjusted HR 0.87 [95% CI, 0.83–0.91], p&lt;0.001; beta-blocker, 0.83 [0.79–0.88], p&lt;0.001; spironolactone, 0.88 [0.83–0.92], p&lt;0.001; echocardiography, 0.90 [0.86–0.94], p&lt;0.001; BNP, 0.92 [0.87–0.96], p&lt;0.001). Kaplan-Meier curves showed that readmission rates were better among higher composite score, compared to lower composite score (Log-rank test=p&lt;0.001). (Figure) Higher composite scores were associated with statistically significant risk reduction of 23% for HF readmission (HR 0.77, 95% CI [0.73–0.81], p&lt;0.001). Figure 1 Conclusion The hospital performance measures were associated with a significant risk reduction of readmission in Japanese patients with HF.

Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients.

The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan–Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan–Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure.

Sex-Specific QRS differences in Japanese heart failure patients with QRSd

Sex-Specific QRS differences in Japanese heart failure patients with QRSd <120 ms

Current Medical and Social Conditions and Outcomes of Hospitalized Heart Failure Patients - Design and Baseline Information of the Cohort Study in Hiroshima.

Background: Information regarding current medical and social conditions and outcome of Japanese heart failure (HF) patients is needed. Methods and Results: The registry and follow-up study regarding the medical and social conditions and outcomes of hospitalized heart failure patients (REAL-HF) is maintained by 8 regional core hospitals, which provide an interprofessional team approach for HF patients, in Hiroshima Prefecture. We planned to enroll all adult patients hospitalized with symptomatic HF (congestive HF and/or low output syndrome) in 1 year from March 2017. We registered the clinical characteristics of each patient, including physical activity (able to walk independently), during the indexed hospitalization. Information regarding living circumstances, cognitive function test, questionnaire for quality of life (QOL), and interprofessional team approaches was also collected. For patients discharged home, we planned to follow all-cause death, all-cause unscheduled readmission, and the conditions of outpatient cardiac rehabilitation and home nursing-care services at 3 and 12 months after discharge. A total of 1,218 patients has been registered initially. Follow-up is ongoing, and data analysis is expected to be completed in 2019. Conclusions: The REAL-HF will provide a significant database on the current real conditions of hospitalized HF patients in a local district of Japan, elucidating medical and social risk factors of worsened QOL and prognosis.