Improved prediction of sudden cardiac death in patients with heart failure through digital processing of electrocardiography.

AIMS: Available predictive models for sudden cardiac death (SCD) in heart failure (HF) patients remain suboptimal. We assessed whether the electrocardiography (ECG)-based artificial intelligence (AI) could better predict SCD, and also whether the combination of the ECG-AI index and conventional predictors of SCD would improve the SCD stratification among HF patients. METHODS AND RESULTS: In a prospective observational study, 4 tertiary care hospitals in Tokyo enrolled 2559 patients hospitalized for HF who were successfully discharged after acute decompensation. The ECG data during the index hospitalization were extracted from the hospitals' electronic medical record systems. The association of the ECG-AI index and SCD was evaluated with adjustment for left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) class, and competing risk of non-SCD. The ECG-AI index plus classical predictive guidelines (i.e. LVEF ≤35%, NYHA Class II and III) significantly improved the discriminative value of SCD [receiver operating characteristic area under the curve (ROC-AUC), 0.66 vs. 0.59; P = 0.017; Delong's test] with good calibration (P = 0.11; Hosmer-Lemeshow test) and improved net reclassification [36%; 95% confidence interval (CI), 9-64%; P = 0.009]. The Fine-Gray model considering the competing risk of non-SCD demonstrated that the ECG-AI index was independently associated with SCD (adjusted sub-distributional hazard ratio, 1.25; 95% CI, 1.04-1.49; P = 0.015). An increased proportional risk of SCD vs. non-SCD with an increasing ECG-AI index was also observed (low, 16.7%; intermediate, 18.5%; high, 28.7%; P for trend = 0.023). Similar findings were observed in patients aged ≤75 years with a non-ischaemic aetiology and an LVEF of >35%. CONCLUSION: To improve risk stratification of SCD, ECG-based AI may provide additional values in the management of patients with HF.

Initiation and Up-Titration of Guideline-Based Medications in Hospitalized Acute Heart Failure Patients　- A Report From the West Tokyo Heart Failure Registry.

BACKGROUND: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure (AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (ß-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35-0.96). Younger age and higher body mass index were significant predictors of drug up-titration. CONCLUSIONS: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.

Impact of Left Ventricular Chamber Size on Outcome in Heart Failure with Preserved Ejection Fraction.

Although heart failure with preserved ejection fraction (HFpEF) has a highly variable phenotype, heterogeneity in left ventricular chamber size (LVCS) and its association with long-term outcome have not been thoroughly investigated. The present study sought to determine the impact of LVCS on clinical outcome in HFpEF.A total of 1505 consecutive HFpEF patients admitted to hospitals in the multicenter WET-HF Registry for acute decompensated HF (ADHF) between 2006 and 2017 were analyzed. The patients (age: 80 [73-86], male: 48%) were divided into larger (L) or smaller (S) LV end-diastolic diameter (LVEDD) groups by the median value 45 mm.Younger age, male sex, higher body mass index, more favorable nutritional status, valvular etiology, and lower LVEF were associated with larger LVEDD. After propensity matching (399 pairs), the L group showed a larger left atrial diameter, E/e', and tricuspid regurgitation pressure gradient and greater severity of mitral regurgitation. The L group had a higher rate of composite endpoint of all-cause death and ADHF re-admission (P = 0.021) and was an independent predictor. On the other hand, in the pre-matched cohort, the S group rather showed higher in-hospital (4% versus 2%. P = 0.004) and post-discharge mortality (P = 0.009).In HFpEF, LVCS was affected by demographic and cardiac parameters. After adjustment for demographic parameters, larger LVCS was associated with worse clinical outcome. Higher mortality in the S group in the pre-matched cohort might be related to the demographic factors suggesting frailty and/or sarcopenia.

Prevalence, Characteristics, and Impact of Frailty in Patients with Functional Tricuspid Regurgitation.

Little is known as regards frailty in patients with functional tricuspid regurgitation (FTR). Thus, in this study, we aimed to investigate the prevalence, characteristics, and impact of frailty on patients with severe FTR.This prospective study included 110 consecutive patients with severe FTR who were assessed via transthoracic echocardiography at an outpatient clinic. Patients were dichotomized using short physical performance battery (SPPB). To better understand the whole picture of frailty in patients with FTR, other frailty scales were also assessed (frailty checklist, clinical frailty scale, gait speed, and Columbia frailty scale). The primary endpoint was the combination of all-cause mortality and heart failure hospitalization.According to each definition of frailty, 28%-46% were identified to be frail. Those with SPPB score of < 9 were older, had greater New York Heart Association (NYHA) functional classification, and had lower albumin level and estimated glomerular filtration rate compared with those with SPPB score of ≥ 9. They also have smaller tricuspid valve coaptation depth and worse right ventricular fractional area change (RV-FAC) than those with SPPB score of ≥ 9 despite having similar TR severity. The primary endpoint at 1 year was noted in 31% of patients. The SPPB score has excellent discriminatory performance for predicting the primary endpoint (area under the curve 0.82, 95% confidence interval [CI] 0.76-0.91) in receiver operating characteristic analysis and was independently associated with the primary endpoint after adjustment in multivariate analysis (adjusted hazard ratio 0.81, 95% CI, 0.73-0.90; P < 0.001).Frailty has been widely prevalent in the elderly patient population with FTR; in fact, it has been determined to be strong parameter for poor outcomes.

In-Hospital Serum Uric Acid Change Predicts Adverse Outcome in Patients With Heart Failure.

BACKGROUND: Elevated serum uric acid (UA) is associated with an increased risk of adverse outcome in patients with heart failure (HF), but it remains unknown whether the change of serum UA level during the treatment of acute decompensated HF (ADHF) predicts adverse events. METHODS AND RESULTS: We retrospectively analyzed consecutive 1562 patients who were hospitalized for ADHF. Serum UA levels both at admission and discharge were available in 1246 patients (78 years of age, range 69-84 years, 40% female). UA values increased or unchanged (group I) in 766 patients and it decreased in the remaining patients (group D). Group I was characterized by older age, higher proportion of females, preserved left ventricular ejection fraction, and the features of less severity of HF such as lower plasma N-terminal pro B-type natriuretic peptide level and lower percentage of catecholamine use. Nevertheless, group I was associated with higher incidence of the primary end point defined as the composite of all-cause death and ADHF rehospitalization (P = .013, log-rank test). UA change, but not UA at discharge, was an independent predictor of the primary end point (hazard ratio 1.30, interquartile range 1.04-1.64, P = .022). Age, estimated glomerular filtration rate, left ventricular ejection fraction, dose of loop diuretics, and thiazide prescription at discharge were independently associated with the UA change. CONCLUSIONS: In patients with HF, UA change through the treatment of ADHF might predict future adverse outcome.

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

AIMS: 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). METHODS AND RESULTS: 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). CONCLUSION: 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.

Differential Prognostic Impact of Atrial Fibrillation in Hospitalized Heart Failure Patients With Preserved Ejection Fraction According to Coronary Artery Disease Status　- Report From the Japanese Nationwide Multicenter Registry.

BACKGROUND: Atrial fibrillation (AF) is an important prognostic determinant in heart failure (HF) with preserved ejection fraction (HFpEF). However, it is unclear which HFpEF phenotypes are affected by AF in terms of long-term clinical outcomes because HFpEF is a heterogeneous syndrome with comorbidities such as coronary artery disease (CAD). In this study we determined the differential prognostic significance of AF in HFpEF patients according to CAD status.Methods and Results:Data for 408 hospitalized HFpEF patients enrolled in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Nationwide Multicenter Registry were analyzed. Patients were divided into 4 groups according to the presence of AF and CAD. The primary outcome was the composite of all-cause death and HF rehospitalization. The incidence of adverse events was higher in the AF-non-CAD than non-AF-non-CAD group (P=0.004). On multivariable Cox regression analysis with prespecified confounders, AF-non-CAD was significantly associated with an increased risk of adverse events than non-AF-non-CAD (adjusted HR, 1.91; 95% CI: 1.02-3.92) regardless of the type of AF. In contrast, risk was comparable between the AF-CAD and non-AF-CAD groups (adjusted HR, 1.24; 95% CI: 0.64-2.47). CONCLUSIONS: In HFpEF patients without CAD, AF was independently related to adverse events, indicating that intensive management of AF would have more beneficial effects particularly in HFpEF patients without CAD.

Prognostic impact of moderate mitral regurgitation on hospitalized heart failure patients with preserved ejection fraction: A report from the JASPER registry.

A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48-59] vs. 46 [42-50] mm, P < 0.001), left ventricular systolic diameter (35 [30-37] vs. 29 [26-34] mm, P = 0.006), left atrial diameter (49 [46-56] vs. 45 [40-50] mm, P < 0.001), and higher tricuspid regurgitation peak gradient (33 [25-40] vs. 27 [21-33] mmHg, P = 0.012). In contrast, levels of plasma B-type natriuretic peptide and left ventricular ejection fraction were comparable between the two groups. In the follow-up period (median 738 days), there were 57 all-cause deaths. In the Kaplan-Meier analysis, all-cause mortality was higher in moderate MR group than in no or mild MR group (log-rank P = 0.023). In the Cox proportional hazard analysis, moderate MR at discharge was a predictor of all-cause mortality (hazard ratio 2.256, 95% confidence interval 1.035-4.917, P = 0.041). Moderate MR at discharge is associated with adverse prognosis in hospitalized patients with HFpEF.

Additive prognostic significance of ejection fraction for ESC risk model in hypertrophic cardiomyopathy patients.

The European Society of Cardiology (ESC) clinical risk model is reported in predicting sudden death of hypertrophic cardiomyopathy (HCM). We examined the validity of this model and investigated the significance of ejection fraction (EF) in predicting the prognosis using ESC risk model in HCM patients. 305 HCM patients (198 males) were followed (median follow-up 4.8 years) for life-threatening arrhythmic events (sudden death, aborted sudden death, sustained VT/VF, appropriate ICD intervention for VT/VF) and were divided using ESC risk model into low- (Group L), intermediate- (Group I) and high- (Group H) risk groups. There was a significant difference in the events rate among the 3 groups (L, 0.9%/year; I, 3.9%/year; H, 6.8%/year; log-rank p < 0.001) in all study patients. Reduced EF (<50%) was identified in 27 (8.9%) cases. There was a significant difference in the events rate among the 3 groups in patients with reduced EF (L, 2.4%/year; I, 4.9%/year; H, 16.1%/year; log-rank p = 0.025). There was a significant difference in the events rate among 2 groups in patients stratified as Group H (preserved EF, 3.1%/year vs. reduced EF, 16.1%/year; log-rank p = 0.041). ESC risk model precisely predicts life-threatening events in patients with HCM. Adding EF to ESC risk model are useful for further risk stratification of life-threatening arrhythmic events.

Impact of Pulmonary Artery-to-Aorta Ratio by CT on the Clinical Outcome in Heart Failure.

INTRODUCTION: Previous studies have indicated that the ratio of pulmonary artery (PA) to ascending aorta (Ao) diameter as measured by computed tomography (PA/Ao) is strongly associated with pulmonary artery pressure. However, the clinical significance of PA/Ao in heart failure (HF) has not been fully characterized. We sought to investigate the prognostic impact of PA/Ao in HF. METHODS: Based on the prospective registry of patients admitted to our institution due to acute decompensated HF (ADHF), the records of the consecutive 761 patients admitted between 2011 and 2016 were reviewed. Thoracic computed tomography data during the hospital stays were obtained from 447 patients (median 78 (70-84) years of age; male, 62.2%). The diameters of PA and Ao were measured at the level of PA bifurcation. The subjects were divided into the H group (PA/Ao ≥ 1.0) and the L group (PA/Ao < 1.0) according to the PA/Ao values. The cutoff value was derived from receiver operating curve analysis. RESULTS: There were no significant differences in age, sex or body mass index between the H and L groups. The H group was associated with significantly larger left atrial dimension (LAD), higher tricuspid regurgitation peak gradient (TRPG) and E/e' (LAD, H, 48 (42-55) mm vs L, 45 (39-50) mm, P < 0.001; TRPG, H, 34 (26-48) mm Hg vs L, 28 (22-38) mm Hg, P < 0.001; E/e', H, 23.3 (42-55) vs L, 18.4 (13.9-25), P < 0.001). Length of hospital stay was significantly longer in the H group than in the L group (H, 19 (14-32) days vs L, 16 (12-23) days, P < 0.001). In-hospital mortality was significantly higher in the H group compared with the L group (H, 5.4% vs L, 1.2%, P = 0.02). Age, sex, LAD and TRPG were independently associated with PA/Ao. The primary endpoint, defined as the composite of all-cause death and ADHF rehospitalization during a median of 479 days after discharge, was significantly more common in the H group (P < 0.001, log-rank test). PA/Ao was independently associated with the primary endpoint, even after adjusting for the other confounding factors (P = 0.002). CONCLUSIONS: PA/Ao is a reliable marker for the prediction of the outcome of patients with ADHF.

Prognostic Impact of Worsening Renal Function in Hospitalized Heart Failure Patients With Preserved Ejection Fraction: A Report From the JASPER Registry.

BACKGROUND: The characteristics and prognostic impact of persistent worsening renal function (WRF; defined as an increase in serum creatinine of >0.3 mg/dL during hospitalization) on heart failure with preserved ejection fraction have not yet been fully examined. METHODS AND RESULTS: This was a post hoc analysis of the Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry. We divided 523 patients with heart failure with preserved ejection fraction: the WRF group (n = 92 [17.6%]) and the non-WRF group (n = 431 [82.4%]). The WRF group showed a higher systolic blood pressure on admission and a higher prevalence of atherosclerotic diseases, respectively. Logistic regression analysis revealed that systolic blood pressure and loop diuretics were associated with WRF development (P < .05). The Kaplan-Meier analysis (median, 732 days) showed a higher all-cause death in the WRF group, as well as a higher composite end point of all-cause death or rehospitalization for HF (log-rank P < .001). The Cox proportional hazard analysis revealed WRF to be a predictor of both all-cause death (hazard ratio, 2.725; 95% confidence interval, 1.709-4.344; P < .001) and the composite end point (hazard ratio, 2.083; 95% confidence interval, 1.488-2.914; P < .001). CONCLUSIONS: Persistent WRF was associated with systolic blood pressure, atherosclerotic diseases, diuretics, and poor postdischarge prognosis in patients with heart failure with preserved ejection fraction.

Heart Failure With Midrange Ejection Fraction in Patients Admitted for Acute Decompensation: A Report from the Japanese Multicenter Registry.

BACKGROUND: Patients having heart failure with midrange ejection fraction (HFmrEF: 40% ≤ EF < 50%) are increasingly being considered a new subset of the population with heart failure. Despite recent advances in heart-failure treatment strategies, the prognosis of these patients has not improved substantially over time. In addition, the significance of this new phenotype in hospitalized patients with acute decompensated heart failure (ADHF), another population whose prognosis has not improved, also remains poorly understood. This study aimed to describe the clinical characteristics, prognosis and treatment responses of patients with HFmrEF hospitalized for ADHF. METHODS: On the basis of consecutive inpatient data from a multicenter ADHF registry, 651 of 3572 patients (17.1%) were classified as having HFmrEF. Prognostic factors predicting composite outcomes, defined as all-cause death and heart failure readmission, as well as all-cause death alone, were analyzed. RESULTS: In the median follow-up duration of 724 days, both composite endpoints and all-cause death alone were comparable in those with heart failure with preserved ejection fraction, HFmrEF and heart failure with reduced ejection fraction. Age, anemia, hyponatremia, elevated blood urea nitrogen, chronic kidney disease, and elevated plasma brain natriuretic peptide levels were significant predictors of composite outcomes in HFmrEF. CONCLUSIONS: Roughly one-sixth of the patients with ADHF had HFmrEF. The long-term prognosis of patients with HFmrEF was not significantly different from that of patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction in the population with ADHF. Risk factors for adverse outcomes in HFmrEF were also similar to those for heart failure with preserved ejection fraction and HFmrEF in the hospitalized population with ADHF.

Long-term Prognostic Significance of Admission Tricuspid Regurgitation Pressure Gradient in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction: A Report From the Japanese Real-World Multicenter Registry.

BACKGROUND: Doppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG) is a representative noninvasive parameter for evaluating pulmonary artery systolic pressure, which can be a determinant of adverse outcomes in chronic heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of TRPG at admission for hospitalized patients with HFpEF are undetermined. METHODS AND RESULTS: We examined 469 consecutive hospitalized patients with decompensated HFpEF (left ventricular ejection fraction ≥ 50%) who underwent TRPG measurement at admission in our HFpEF multicenter registry. The primary outcome of interest was all-cause death. Admission TRPG was significantly correlated with estimated pulmonary capillary wedge pressure and left atrial dimension (r = 0.24, P < 0.001 and r = 0.21, P < 0.001, respectively). During a median follow-up period of 748 (IQR 540-820) days, 83 patients died. Higher TRPG was significantly associated with higher mortality compared to lower TRPG (log-rank; P = 0.007). Multivariable analysis revealed that elevated TRPG was an independent determinant of mortality (HR 1.02, 95% CI 1.01-1.04, P = 0.008) after adjustment for prespecified confounders and renal function. CONCLUSIONS: Elevated TRPG at admission was an independent determinant of mortality in hospitalized patients with HFpEF, indicating that TRPG at admission could be a useful marker for risk stratification in these patients.

Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute Heart Failure Patients.

BACKGROUND: Precise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission. METHODS AND RESULTS: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = -0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = -0.04) but not for HFpEF patients. CONCLUSIONS: In Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.

Effect of Statins on Mortality in Heart Failure With Preserved Ejection Fraction Without Coronary Artery Disease　- Report From the JASPER Study.

BACKGROUND: Statins might be associated with improved survival in patients with heart failure with preserved ejection fraction (HFpEF). The effect of statins in HFpEF without coronary artery disease (CAD), however, remains unclear. Methods and Results: From the JASPER registry, a multicenter, observational, prospective cohort with Japanese patients aged ≥20 years requiring hospitalization with acute HF and LVEF ≥50%, 414 patients without CAD were selected for outcome analysis. Based on prescription of statins at admission, we divided patients into the statin group (n=81) or no statin group (n=333). We followed them for 25 months. The association between statin use and primary (all-cause mortality) and secondary (non-cardiac death, cardiac death, or rehospitalization for HF) endpoints was assessed in the entire cohort and in a propensity score-matched cohort. In the propensity score-matched cohort, 3-year mortality was lower in the statin group (HR, 0.21; 95% CI: 0.06-0.72; P=0.014). The statin group had a significantly lower incidence of non-cardiac death (P=0.028) and rehospitalization for HF (P<0.001), but not cardiac death (P=0.593). The beneficial effect of statins on mortality did not have any significant interaction with cholesterol level or HF severity. CONCLUSIONS: Statin use has a beneficial effect on mortality in HFpEF without CAD. The present findings should be tested in an adequately powered randomized clinical trial.

Prognostic Impact of Previous Hospitalization in Acute Heart Failure Patients.

BACKGROUND: The natural course of heart failure (HF) is typically associated with repeated hospitalizations, and subsequently, patient prognosis deteriorates. However, the precise relationship between repeated admissions for HF and long-term prognosis remains unknown. Methods and Results: We analyzed data from 1,730 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry between June 2005 and April 2014 (median age, 76 years). Patients were divided into 3 groups according to the number of previous HF admissions at the time of the index admission (0, n=876 [55.4%]; 1, n=425 [26.9%]; ≥2, n=279 [17.7%] previous admissions). A history of multiple previous admissions was an independent predictor for all-cause death and HF readmission in reference to a history of a single previous admission (hazard ratio (HR), 1.53; 95% confidence interval (CI) 1.10-2.13; HR, 1.90 95% CI, 1.47-2.44, respectively) or no previous admissions (HR, 1.37, 95% CI, 1.01-1.85; HR, 2.83, 95% CI, 2.19-3.65, respectively). On the other hand, a history of a single previous admission was an independent predictor for HF readmission in reference to a history of no previous admissions (HR, 1.51, 95% CI, 1.18-1.92), but not for all-cause death (HR, 0.89, 95% CI, 0.66-1.20). CONCLUSIONS: Based on a contemporary multicenter HF registry, a history of multiple previous HF admissions was revealed as an independent, strong risk factor of adverse events following the index admission. The number of hospitalizations could be a simple and important surrogate indicating subsequent adverse events in patients with HF.

Length of hospital stay and its impact on subsequent early readmission in patients with acute heart failure: a report from the WET-HF Registry.

Heart failure (HF) is characterized by frequent rehospitalization and prolonged hospital stay. Although length of stay has been used as a surrogate marker for hospital performance, its association with early rehospitalization remains unknown. We investigated their precise association using contemporary Japanese HF registry. We analyzed the 2785 acute HF patients who were registered in the West Tokyo Heart Failure registry and discharged or transferred to the recuperation facilities (mean age, 73.8 ± 13.5 years; 60.8% were men). Median length of stay was 15 days (interquartile range, 10-23 days). One-hundred and fourteen patients (4.1%) were readmitted for worsening HF within 30 days after discharge. Thirty-day risk-adjusted HF readmission after a shorter length of stay (1-12 days; the lower tertile within the cohort) was higher than those after intermediate (13-19 days; the middle tertile) [HR 1.71, 95% confidence interval (CI) 1.05-2.77]. Even after a longer length of stay, there tended to be a higher risk of 30-day HF readmission (HR 1.59, 95% CI 0.96-2.65). In conclusion, the Japanese acute HF patients had low rates of early-HF readmission after quite a long length of stay at urban tertiary care centers. Shorter length of stay was associated with increased rates of 30-day HF readmission, while longer length of stay also the same trended.Clinical Trial Registration: https://www.umin.ac.jp/icdr/index-j.html . Unique identifier: UMIN000001171.

Effective blood hemoglobin level to predict prognosis in heart failure with preserved left ventricular ejection fraction: results of the Japanese heart failure syndrome with preserved ejection fraction registry.

High prevalence of anemia in heart failure with preserved left ventricular ejection fraction (HFpEF) has been reported. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. In addition, effective blood hemoglobin (Hb) level for prognosis in HFpEF patients remains largely unknown. In this study, we investigated the association between anemia, gender, and prognosis in 535 HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. Furthermore, we assessed effective blood Hb level to predict prognosis in HFpEF patients. According to the World Health Organization criteria, the prevalence rate of anemia on admission was about 70% in both male and female HFpEF patients. Kaplan-Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients. Interestingly, multivariate analysis revealed that blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level at discharge of 9.4 g/dL for male and 12.3 g/dL for female was more accurate cutoff value to predict all-cause mortality in HFpEF patients. Anemia was implicated in poor prognosis in both male and female HFpEF patients. In particular, blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. Effective cutoff value of blood Hb level at discharge to predict all-cause mortality was lower in male than in female HFpEF patients.

Relation of Systolic Blood Pressure on the Following Day with Post-Discharge Mortality in Hospitalized Heart Failure Patients with Preserved Ejection Fraction.

The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP > 140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP < 100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank < 0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.

Anemia Is Associated With Blunted Response to ß-Blocker Therapy Using Carvedilol　- Insights From Japanese Chronic Heart Failure (J-CHF) Study.

BACKGROUND: Anemia portends a poor clinical outcome in patients with chronic heart failure (CHF). However, its mechanism remains unknown. We sought to elucidate the effect of anemia on patients with HF with reduced ejection fraction (HFrEF) who receive carvedilol therapy.Methods and Results:J-CHF study was a prospective, randomized, multicenter trial that assigned 360 HFrEF patients to 2.5 mg/5 mg/20 mg carvedilol groups according to the target dose. At baseline 70 patients (19%) had anemia ([A]) defined as hemoglobin level (Hb) <13 g/dL (male) or <12 g/dL (female) and the remaining 290 did not ([N]). Allocated and achieved doses of carvedilol were similar. Left ventricular ejection fraction (LVEF) and plasma B-type natriuretic peptide (BNP) level significantly improved in both groups over 56 weeks, but they were smaller in [A] than in [N] (LVEF, P=0.046; BNP, P<0.0001 by ANOVA). Baseline Hb was an independent predictor of absolute change in LVEF (ß=0.13, P=0.047) and BNP (ß=-0.10, P=0.01). Presence of chronic kidney disease defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2at baseline was not associated with differential response to carvedilol therapy. During 3.8±1.4 years follow-up, group [A] had a higher incidence of the composite endpoint of death, hospitalization for cardiovascular causes including HF compared with [N] (P=0.006). Baseline Hb was an independent predictor of the composite endpoint (hazard ratio 0.86, P=0.04), whereas baseline eGFR was not. CONCLUSIONS: Our data suggested that anemia was associated with a blunted response to carvedilol in HFrEF patients.