Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. METHODS: Using the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N = 88; lower GI cancer: N = 114; non-GI cancer: N = 947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. RESULTS: The upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4 %, lower GI cancer: 15.4 %, and non-GI cancer: 11.6 %, P = 0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53 %), followed by the lower GI (24 %). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95 %CI, 1.31-3.87, P = 0.003), but that in lower GI cancer was insignificant. CONCLUSIONS: Upper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

The Prognostic Impact of Follow-up Cardiac MIBG Imaging on LV trajectory After Acute Decompensation.

AIMS: Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure. Recently, the trajectory of left ventricular ejection fraction (LVEF) has been a focus in patients with reduced LVEF admitted for acute decompensated heart failure (ADHF). We sought to investigate the prognostic value of follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF in relation to LVEF trajectory. METHODS AND RESULTS: We prospectively studied 145 ADHF patients with reduced LVEF<40%. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image at discharge and at the 6-month follow-up (6FUP). At 6 months after discharge, 54 (37%) patients had complete recovery of LVEF≥50% (HFcorEF), and 43 (30%) patients had partial recovery of LVEF: 40%-50% (HFparEF), while the remaining 48 (33%) patients had no functional recovery of LVEF (HFnorEF). The late HMR at 6 FUP in HFcorEF patients was significantly greater than that in HFparEF and HFnorEF patients. During a follow-up period of 4.3 ± 2.6 years, 43 patients had cardiac events, defined as the composite of readmission for worsening HF and cardiac death. Patients with lower late HMR at 6 FUP had a greater risk of cardiac events than those with higher late HMR at 6 FUP in the group with recovered LVEF, especially HFparEF, which was not observed in the HFnorEF subgroup. CONCLUSION: Follow-up MIBG imaging after discharge could provide additional prognostic information in ADHF patients with recovered left ventricular function.

A Rare Case of a Common Inferior Pulmonary Vein Presumed to Be a Remnant of the Common Pulmonary Vein.

A 74-year-old woman with an implanted physiological DDD pacemaker visited our department complaining of palpitations due to atrial fibrillation (AF). Catheter ablation therapy for AF was scheduled. Preoperative multidetector computed tomography showed that the inferior pulmonary vein (PV) was a common trunk, and the left and right superior PVs branched from the center of the left atrial roof. In addition, mapping of the left atrium before AF ablation revealed no potential in either the inferior PV or common trunk. We performed left and right superior PV and posterior wall isolation. After ablation, AF was not observed on pacemaker recordings.

The clinical relevance of mild cognitive impairment in acute heart failure: A comparison with cognitive impairment.

BACKGROUND: Although mild cognitive impairment (MCI) has received much attention as a precursor of dementia, its prognostic role has not been fully clarified in patients with heart failure (HF). METHODS AND RESULTS: We studied 274 patients admitted for acute decompensated HF. Cognitive function was evaluated using Mini Mental State Examination (MMSE). According to the previous definition, MMSE of 0-23, 24-27, and 28-30 were classified as CI (n = 132), MCI (n = 81), and normal cognitive function (n = 61). The primary endpoint was cardiac events, defined as the composite of unplanned HF hospitalization and cardiovascular mortality. During a mean follow-up period of 4.9 ±â€¯3.1 years, 145 patients experienced cardiac events. Multivariable logistic regression analysis showed that hypertension (p = 0.043), low cardiac index (p = 0.022), and low serum albumin level (p = 0.041) had a significant association with cognitive abnormalities. Both CI and MCI were significantly associated with cardiac events after Cox multivariable adjustment [CI: p = 0.001, adjusted HR 2.66 (1.48-4.77); MCI: p = 0.025, adjusted HR 1.90 (1.09-3.31), normal cognitive function group: reference]. Patients with MCI had a significantly higher risk of unplanned HF hospitalization [p = 0.033, adjusted HR 1.91 (1.05-3.47)], but not all-cause mortality (p = 0.533) or cardiovascular mortality (p = 0.920), while CI was significantly associated with all-cause mortality (p = 0.025) and cardiovascular mortality (p = 0.036). CONCLUSION: Even MCI had a significant risk of cardiac events in patients with acute decompensated HF. This risk was mainly derived from unplanned HF hospitalization.

Changing Trends in Mechanical Circulatory Support Use and Outcomes in Patients Undergoing Percutaneous Coronary Interventions for Acute Coronary Syndrome Complicated With Cardiogenic Shock: Insights From a Nationwide Registry in Japan.

BACKGROUND: Temporal trends in the management of acute coronary syndrome complicated with cardiogenic shock after the revision of guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella require further investigation, because their impact remains uncertain. METHODS AND RESULTS: Using the Japanese Percutaneous Coronary Intervention (J-PCI) registry database from 2019 to 2021, we identified 12 171 patients undergoing percutaneous coronary intervention for acute coronary syndrome complicated with cardiogenic shock under mechanical circulatory support. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella, and (3) venoarterial extracorporeal membrane oxygenation (VA-ECMO); the VA-ECMO group was further stratified into (3a) VA-ECMO alone, (3b) VA-ECMO in combination with IABP, and (3c) VA-ECMO in combination with Impella. The quarterly prevalence and outcomes were reported. The use of IABP alone decreased significantly from 63.5% in the first quarter of 2019 to 58.3% in the fourth quarter of 2021 (P for trend=0.01). Among 4245 patients requiring VA-ECMO, the use of VA-ECMO in combination with IABP decreased significantly from 78.7% to 67.3%, whereas the use of VA-ECMO in combination with Impella increased significantly from 4.2% to 17.0% (P for trend <0.001 for both). After adjusting for the confounders, the risk difference in the fourth quarter of 2021 relative to the first quarter of 2019 for in-hospital mortality was not significant (adjusted odds ratio, 0.84 [95% CI, 0.69-1.01]). CONCLUSIONS: Our study revealed substantial changes in the use of different mechanical circulatory support modalities in acute coronary syndrome complicated with cardiogenic shock, but they did not significantly improve the outcomes.

Trends in Mechanical Circulatory Support Use and Outcomes of Patients With Cardiogenic Shock in Japan, 2010 to 2020 (from a Nationwide Inpatient Database Study).

Little is known about the impact of the downgrade of guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella in Japan, where IABPs have been predominantly used. This study aimed to describe the annual trends in the mechanical circulatory support (MCS) use and outcomes in patients with cardiogenic shock (CS) requiring MCS. Using the Japanese Diagnosis Procedure Combination database from July 2010 to March 2021, we identified inpatients with CS requiring MCS. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella alone, and (3) extracorporeal membrane oxygenation (ECMO), regardless of IABP or Impella use. The patient characteristics and outcomes were reported by the fiscal year. Of the 160,559 eligible patients, 117,599 (73.2%) used IABP alone, 1,465 (0.9%) Impella alone, and 41,495 (25.8%) ECMO. The prevalence of the use of an IABP alone significantly decreased from 80.5% in 2010 to 65.3% in 2020 (p for trend <0.001), whereas the prevalence of the use of an Impella alone significantly increased from 0.0% to 5.0% and ECMO from 19.5% to 29.6% (p for trend <0.001 for both). In-hospital mortality significantly increased from 29.3% in 2010 to 32.6% in 2020 in the overall patients with CS requiring MCS but significantly decreased in those requiring ECMO from 73.7% to 64.1% (p for trend <0.001 for both). In conclusion, there were significant annual changes in the patterns of MCS use and clinical outcomes in patients with CS requiring MCS.

Trends in Treatment Patterns and Outcomes of Patients With Pulmonary Embolism in Japan, 2010 to 2020: A Nationwide Inpatient Database Study.

Background The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE. Methods and Results Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high-risk PE were defined as those admitted for out-of-hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non-high-risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high-risk PE, and the remaining 80 850 (90.9%) had non-high-risk PE. Between 2010 and 2020, in patients with high-risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 51.0% to 43.7% (P for trend=0.04). In patients with non-high-risk PE, the annual proportion of direct oral anticoagulant use increased from 0.0% to 38.3%, whereas that of thrombolysis use significantly decreased from 13.7% to 3.4% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 7.9% to 5.4% (P for trend <0.001). Conclusions Substantial changes in the PE practice and outcomes occurred in patients with high-risk and non-high-risk PE.

Effectiveness of systemic thrombolysis on clinical outcomes in high-risk pulmonary embolism patients with venoarterial extracorporeal membrane oxygenation: a nationwide inpatient database study.

BACKGROUND: Current guidelines recommend systemic thrombolysis as the first-line reperfusion treatment for patients with high-risk pulmonary embolism (PE) who present with cardiogenic shock but do not require venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, little is known about the optimal reperfusion treatment in high-risk PE patients requiring VA-ECMO. We aimed to evaluate whether systemic thrombolysis improved high-risk PE patients' outcomes who received VA-ECMO. METHODS: This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. We identified patients who were diagnosed with PE and received VA-ECMO on the day of admission. Patients who received systemic thrombolysis with monteplase or urokinase within two days of initiating VA-ECMO were defined as the thrombolysis group and the remaining patients as the control group. The primary outcome was in-hospital mortality and secondary outcomes were favorable neurological outcomes, length of hospital stay, VA-ECMO duration, total hospitalization cost, major bleeding, and blood transfusion volume. Propensity-score inverse probability of treatment weighting (IPTW) was performed to compare the outcomes between the groups. RESULTS: Of 1220 eligible patients, 432 (35%) received systemic thrombolysis within two days of initiating VA-ECMO. Among the unweighted cohort, patients in the thrombolysis group were less likely to have poor consciousness at admission, out-of-hospital cardiac arrest, and left heart catheterization. After IPTW, the patient characteristics were well-balanced between the two groups The crude in-hospital mortality was 52% in the thrombolysis group and 61% in the control group. After IPTW, in-hospital mortality did not differ significantly between the two groups (risk difference: - 3.0%, 95% confidence interval: - 9.6% to 3.5%). There were also no significant differences in the secondary outcomes. Sensitivity analyses showed a significant difference in major bleeding between the monteplase and control groups (risk difference: 6.9%, 95% confidence interval: 1.7% to 12.1%), excluding patients who received urokinase. There were no significant differences in the other sensitivity and subgroup analyses except for the total hospitalization cost. CONCLUSIONS: Systemic thrombolysis was not associated with reduced in-hospital mortality or increased major bleeding in the high-risk PE patients receiving VA-ECMO. However, systemic thrombolysis with monteplase was associated with increased major bleeding.

The clinical relevance of quality of life in heart failure patients with preserved ejection fraction.

AIMS: Patient reported outcomes (PROs) are gradually being incorporated into daily practice to assess individual health-related quality of life (QOL). However, despite accumulating evidence of the prognostic utility of heart failure (HF)-specific QOL indices, evidence on the generic QOL score is scarce, especially in patients with HF with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Patient data were extracted from the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. EuroQol 5 dimensions 5-level (EQ-5D-5L) data were obtained at discharge to evaluate patients' health-related QOL. The study population (n = 864) was divided into tertiles based on their EQ-5D-5L index as follows: low EQ-5D-5L 0.038-0.664 (n = 287), middle EQ-5D-5L 0.665-0.867 (n = 293), and high EQ-5D-5L 0.871-1.000 (n = 284). A total of 206 patients died over a mean follow-up period of 2.0 ± 1.2 years. Kaplan-Meier analysis revealed that the risk of mortality increased with the tertile of the EQ-5D-5L index (34% vs. 23% vs. 14%, P < 0.001). Cox multivariable analysis revealed that patients with EQ-5D-5L index in the low and middle tertiles had a significantly greater risk of mortality than those with EQ-5D-5L index in the high tertile [low EQ-5D-5L: adjusted hazard ratio (HR): 1.81 (1.12-2.92), P = 0.002, middle EQ-5D-5L: adjusted HR 1.91 (1.21-3.03), P = 0.006]. Among the dimensions of EQ-5D-5L, mobility (P = 0.014), self-care (P = 0.023) and usual activities (P = 0.008) were significant factors associated with all-cause mortality after multivariable adjustment. CONCLUSIONS: EQ-5D-5L is useful tool for risk stratification in patients with HFpEF.

Loop Diuretic Use is Associated With Adverse Clinical Outcomes in Acute Myocardial Infarction Patients With Low Volume Status.

To investigate the difference in the prognostic impact of loop diuretics in patients with acute myocardial infarction (AMI) based on plasma volume status, a total of 3,364 survivors of AMI who were registered in the large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed by the estimated plasma volume status (ePVS) that was calculated based on a weight- and hematocrit-based formula at discharge. The endpoint was a composite endpoint of all-cause death and rehospitalization due to heart failure for 5 years. During a median follow-up period of 1.9 years, 90 and 223 patients had events in the groups with low ePVS (

Prognostic significance of serum chloride level in heart failure patients with preserved ejection fraction.

AIMS: The prognostic value of serum chloride level has been reported primarily in patients with heart failure with reduced ejection fraction, and hence, there is limited evidence in patients of heart failure with preserved ejection fraction (HFpEF). This study was conducted to clarify the relationship between serum chloride level and clinical outcomes in patients with HFpEF with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Patient data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, a prospective multicentre observational registry for ADHF-HFpEF in Osaka. The data of 870 patients were analysed after excluding patients with in-hospital death, missing follow-up data, missing data of serum chloride level, or on chronic dialysis therapy. The primary endpoint of this study was all-cause mortality. At discharge, right ventricular systolic dysfunction was significantly associated with the lowest tertile of serum chloride level after multivariable adjustment (P = 0.0257). During a mean follow-up period of 1.8 ± 1.0 years, 186 patients died. Cox multivariable analysis showed that serum chloride level at discharge (P = 0.0017) was independently associated with all-cause mortality after multivariable adjustment of major confounders, whereas serum sodium level was no longer significant (P = 0.6761). Kaplan-Meier survival curve analysis revealed a significantly increased risk of mortality stratified by the tertile of serum chloride level [29% vs. 19% vs. 16%, P = 0.0002; hazard ratio (HR): 2.09 (95% confidence interval, CI: 1.31 to 3.34), HR: 1.03 (95% CI: 0.65 to 1.64)]. CONCLUSIONS: Serum chloride level was useful for the prediction of poor outcome in ADHF patients with preserved ejection fraction.

Usefulness of the 2-year iodine-123 metaiodobenzylguanidine-based risk model for post-discharge risk stratification of patients with acute decompensated heart failure.

PURPOSE: A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores. METHODS: We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- (< 4%), intermediate- (4-12%), and high-risk (> 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated. RESULTS: There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model (p < 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores. CONCLUSION: The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF. TRIAL REGISTRATION NUMBER: UMIN000015246, 25 September 2014.

Prognostic Significance of Cardiac 123I-MIBG SPECT Imaging in Heart Failure Patients With Preserved Ejection Fraction.

OBJECTIVES: The authors sought to elucidate the prognostic value of cardiac sympathetic nerve dysfunction as evaluated using iodine-123-labeled metaiodobenzylguanidine (123I-MIBG) single-photon emission computed tomography (SPECT) imaging in patients with heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). BACKGROUND: Cardiac sympathetic nerve dysfunction assessed by 123I-MIBG imaging is associated with poor outcomes in chronic HF patients with reduced left ventricular ejection fraction (HFrEF). However, no information is available on the prognostic vale of cardiac 123I-MIBG SPECT imaging in patients with HFpEF. METHODS: We studied 148 patients admitted for acute decompensated HF (ADHF) with nonischemic HFpEF and who underwent cardiac 123I-MIBG imaging at discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (H/M) was measured on the delayed planar image (late H/M). SPECT analysis of the delayed image was conducted, and the tracer uptake in all 17 regions on the polar map was scored on a 5-point scale by comparison with a sex-matched normal control database. The total defect score (TDS) was calculated by summing the score of each of the 17 segments. The primary endpoint was the association between TDS and cardiac events (the composite of emergent HF hospitalization and cardiac death). RESULTS: During a mean follow-up period of 2.4 ± 1.6 years, 61 patients experienced cardiac events. TDS was significantly associated with cardiac events after multivariate Cox adjustment (P < 0.0001). Patients with high TDS levels had a significantly greater risk of cardiac events than those with middle or low TDS levels (63% vs 40% vs 20%, respectively; P < 0.0001; HR: 4.69; 95% CI: 2.29 to 9.61; and HR: 2.46; 95% CI: 1.14 to 5.29). C-statistic of TDS was 0.730 (95% CI: 0.651 to 0.799), which was significantly higher than that of late H/M (0.607; 95% CI: 0.524 to 0.686; P = 0.0228). CONCLUSIONS: Cardiac 123I-MIBG SPECT imaging provided useful prognostic information in nonischemic ADHF patients with HFpEF. (Clinical Trial: Osaka Prefectural Acute Heart Failure Syndrome Registry [OPAR]: UMIN000015246).

Coronary vasomotion after treatment with drug-coated balloons or drug-eluting stents: a prospective, open-label, single-centre randomised trial.

BACKGROUND: Although recent studies have reported that drug-coated balloons (DCB) are non-inferior to drug-eluting stents (DES) for the treatment of native coronary arteries in a specific population, there is no available information concerning vasomotion after treatment with DCB. AIMS: The aim of this study was to prospectively compare coronary vasomotion in patients with small coronary artery disease treated with DCB versus DES. METHODS: Forty-two native lesions (2.0-3.0 mm) treated in our institution were randomly assigned to the DCB arm (n=19) or the bioabsorbable polymer everolimus-eluting stents arm (n=23) after successful predilation. At eight months after treatment, endothelium-dependent and -independent vasomotion was evaluated with intracoronary infusions in incremental doses of acetylcholine (right coronary artery: low dose 5 µg, high dose 50 µg; left coronary artery: low dose 10 µg, high dose 100 µg) and nitroglycerine (200 µg). The mean lumen diameter of the distal segment, beginning 5 mm and ending 15 mm distal to the edge of the treated segment, was quantitatively measured by angiography. RESULTS: The luminal dimension in the treated segment did not differ between groups at the follow-up angiography. The vasoconstriction after acetylcholine infusion was less pronounced in the DCB arm than in the DES arm (low-dose: 6±13% vs -3±18%, p=0.060; high-dose: -4±17% vs -21±29%, p=0.035). The response to nitroglycerine did not differ between groups (17±13% vs 17±22%, p=0.929). CONCLUSIONS: Vasoconstriction after acetylcholine infusion in the peri-treated region was less pronounced in the DCB arm than in the DES arm, suggesting that endothelial function in treated coronary vessels could be better preserved by DCB than by new-generation DES.

Effect of Empagliflozin as an Add-On Therapy on Decongestion and Renal Function in Patients With Diabetes Hospitalized for Acute Decompensated Heart Failure: A Prospective Randomized Controlled Study.

BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. METHODS: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. RESULTS: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (P=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (P=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (P=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. CONCLUSIONS: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.

Clinical impact of estimated plasma volume status and its additive effect with the GRACE risk score on in-hospital and long-term mortality for acute myocardial infarction.

BACKGROUND: Estimated plasma volume status (ePVS) is a well-validated prognostic indicator in heart failure. However, it remains unclear whether ePVS has prognostic significance in patients with acute myocardial infarction (AMI). Moreover, there is no available information on its additive effect with the Global Registry of Acute Coronary Events (GRACE) risk score in AMI patients. METHODS: Data were obtained from the Osaka Acute Coronary Insufficiency Study (OACIS) registry database. Patients whose data were available for ePVS derived from Hakim's formula and the GRACE risk score were studied. The primary endpoints were in-hospital and 5-year mortality. RESULTS: Of 3930 patients, 206 and 200 patients died during hospitalization and 5 years after discharge, respectively. After adjustment, ePVS remained an independent predictor of in-hospital death (OR:1.02, 95% CI: 1.00-1.04, p = 0.036), and 5-year mortality(HR:1.03, 95% CI: 1.01-1.04, p < 0.001). An additive effect of ePVS with the GRACE risk score was observed in predicting the 5-year mortality with an area under the receiver operating characteristic curve (AUC) from 0.744 to 0.763 (p = 0.026), but not in-hospital mortality (the AUC changed from 0.875 to 0.875, p = 0.529). The incremental predictive value of combining ePVS and the GRACE risk score for 5-year mortality was significantly improved, as shown by the net reclassification improvement (NRI:0.378, p < 0.001) and integrated discrimination improvement (IDI:0.014, p < 0.001). CONCLUSIONS: In patients with AMI, ePVS independently predicted in-hospital and long-term mortality. In addition, ePVS had an additive effect with the GRACE risk score on long-term mortality. Therefore, ePVS may be useful for identifying high-risk subjects for intensive treatment.

Prognostic value of impaired hepato-renal function and liver fibrosis in patients admitted for acute heart failure.

AIMS: Cardiohepatic interactions have been a focus of attention in heart failure (HF). The model for end-stage liver disease excluding international normalized ratio (MELD-XI) score has been shown to be useful for predicting poor outcomes in patients with acute decompensated HF (ADHF). Furthermore, the fibrosis-4 (FIB-4) index, a simple marker to assess liver fibrosis, predicts adverse prognoses in patients with HF as well. However, there is little information available on the prognostic significance of the combination of the MELD-XI score and FIB-4 index in patients with ADHF and its association with left ventricular ejection fraction (LVEF) subgroup. METHODS AND RESULTS: We prospectively studied 466 consecutive patients who were admitted for ADHF [HF with reduced LVEF (LVEF < 40%): n = 164, HF with mid-range LVEF (40% ≤ LVEF < 50%): n = 104, and HF with preserved LVEF (LVEF ≥ 50%): n = 198]. We calculated the MELD-XI score and FIB-4 indices at discharge. The primary endpoint was all-cause death (ACD). During the mean follow-up period of 2.8 years, 143 patients had ACD. In the multivariate Cox analysis, the MELD-XI score and FIB-4 index were independently associated with ACD. Patients were stratified into the following three groups according to the median value of MELD-XI score (=11) and FIB-4 index (=2.13): Group 1 had both a low MELD-XI score and a low FIB-4 index; Group 2 had either a high MELD-XI score (MELD-XI score ≥11) or a high FIB-4 index (FIB-4 index ≥2.13); and Group 3 had both a high MELD-XI score and a high FIB-4 index. Kaplan-Meier analysis revealed that Group 2 and Group 3 had a significantly greater risk of ACD than Group 1 [Group 2 vs. Group 1: adjusted hazard ratio, 2.48 (95% confidence interval: 1.75-3.53), P < 0.0001; Group 3 vs. Group 1: adjusted hazard ratio, 7.03 (95% confidence interval: 3.95-13.7), P < 0.0001]. In addition, the patients with both a higher MELD-XI score and FIB-4 index showed a significantly higher risk of ACD also in the patients with HF with reduced LVEF, HF with mid-range LVEF, and HF with preserved LVEF (all P < 0.0001). CONCLUSIONS: The combination of MELD-XI score and FIB-4 index may be useful for stratifying patients at risk for ACD in patients with ADHF, irrespective of LVEF.

Incremental prognostic value of cardiac metaiodobenzylguanidine imaging over the co-morbid burden in acute decompensated heart failure.

AIMS: Co-morbidities are associated with poor clinical outcomes in patients with chronic heart failure, while cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging provides prognostic information in such patients. We sought to prospectively investigate the incremental prognostic value of cardiac MIBG imaging over the co-morbid burden, in patients admitted for acute decompensated heart failure (ADHF). METHODS AND RESULTS: In 433 consecutive ADHF patients with survival to discharge, we measured the co-morbidity using age-adjusted Charlson co-morbidity index (ACCI), commonly employed to evaluate a weighted and scored co-morbid condition, adding additional points for age. In cardiac MIBG imaging, the cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image. Over a follow-up period of 2.9 ± 1.5 years, 160 patients had a cardiac event (a composite of cardiac death and unplanned hospitalization for worsening heart failure). Patients with high ACCI (≥6: median value) had a significantly greater risk of a cardiac event. In multivariate Cox analysis, the ACCI and late HMR were significantly and independently associated with a cardiac event. In both high and low ACCI subgroups (ACCI ≥ 6 and <6, respectively), patients with low late HMR had a significantly greater risk of a cardiac event (high ACCI: 51% vs. 34% P = 0.0026, adjusted HR 1.74 [1.21-2.51]; low ACCI: 34% vs. 17%, P = 0.0228, adjusted HR 2.19 [1.10-4.37]). CONCLUSIONS: Cardiac MIBG imaging could provide additional prognostic information over ACCI, which was also promoted to be a useful risk model, in patients admitted for ADHF.

Prognostic significance of cardiac I-123-metaiodobenzylguanidine imaging in patients with reduced, mid-range, and preserved left ventricular ejection fraction admitted for acute decompensated heart failure: a prospective study in Osaka Prefectural Acute Heart Failure Registry (OPAR).

AIMS: Cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging provides prognostic information in patients with chronic heart failure (HF). However, there is little information available on the prognostic role of cardiac 123I-MIBG imaging in patients admitted for acute decompensated heart failure (ADHF), especially relating to reduced ejection fraction [HFrEF; left ventricular ejection fraction (LVEF) < 40%], mid-range ejection fraction (HFmrEF; 40% ≤ LVEF < 50%) and preserved ejection fraction (HFpEF; LVEF ≥ 50%). METHODS AND RESULTS: We studied 349 patients admitted for ADHF and discharged with survival. Cardiac 123I-MIBG imaging, echocardiography, and venous blood sampling were performed just before discharge. The cardiac 123I-MIBG heart-to-mediastinum ratio (late H/M) was measured on the chest anterior view images obtained at 200 min after the isotope injection. The endpoint was cardiac events defined as unplanned HF hospitalization and cardiac death. During a follow-up period of 2.1 ± 1.4 years, 128 patients had cardiac events (45/127 in HFrEF, 28/78 in HFmrEF, and 55/144 in HFpEF). On multivariable Cox analysis, late H/M was significantly associated with cardiac events in overall cohort (P = 0.0038), and in subgroup analysis of each LVEF subgroup (P = 0.0235 in HFrEF, P = 0.0119 in HFmEF and P = 0.0311 in HFpEF). Kaplan-Meier analysis showed that patients with low late H/M (defined by median) had significantly greater risk of cardiac events in overall cohort (49% vs. 25% P < 0.0001) and in each LVEF subgroup (HFrEF: 48% vs. 23% P = 0.0061, HFmrEF: 51% vs. 21% P = 0.0068 and HFpEF: 50% vs. 26% P = 0.0026). CONCLUSION: Cardiac sympathetic nerve dysfunction was associated with poor outcome in ADHF patients irrespective of HFrEF, HFmrEF, or HFpEF.