Remote ischemic periconditioning suppresses cardiac sympathetic activation in acute myocardial infarction: a randomized controlled trial.

PURPOSE: Remote ischemic periconditioning (RIPC) has demonstrated cardioprotective effects and improved clinical outcomes as an adjunct to emergent percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI). However, whether RIPC affects the cardiac sympathetic nerve activity in patients with STEMI remains unclear. This study investigated the effects of RIPC on cardiac sympathetic nerve activity in patients with STEMI. METHODS: We prospectively assigned patients with STEMI who underwent emergent PCI to receive RIPC or no procedure (control group) upon arrival at the cardiac catheterization laboratory. The primary endpoint was cardiac sympathetic nerve activity assessed through the washout rate (WR) in cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging. RESULTS: Patients in the RIPC (n = 62) and control (n = 60) groups had similar demographic and clinical characteristics at baseline. Multivariable linear regression models revealed that the culprit lesion of the left anterior descending artery and hemoglobin level were significantly and independently associated with WR at discharge. WRs of the groups differed insignificantly at discharge. However, the RIPC group (n = 49) showed significantly lower WR than the control group (n = 47) at 1 year after discharge (p = 0.027). In the single-photon emission computed tomography analysis at 1 year after discharge, the RIPC group demonstrated significantly higher late uptake (p = 0.021) and lower WR (p = 0.013) in the nonculprit lesion, with a non-significant decrease in WR for the culprit lesion. CONCLUSION: RIPC can suppress augmented cardiac sympathetic nerve activity in patients with STEMI, particularly in nonculprit lesions.

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.

Prediction of sudden cardiac death in chronic heart failure patients with reduced ejection fraction by ADMIRE-HF risk score and early repolarization pattern.

BACKGROUND: AdreView myocardial imaging for risk evaluation in heart failure (ADMIRE-HF) risk score is a novel risk score to predict serious arrhythmic risk in chronic heart failure patients with reduced ejection fraction (HFrEF). Moreover, early repolarization pattern (ERP) has been shown to be associated with an increased risk of sudden cardiac death (SCD) in HFrEF patients. We sought to investigate the prognostic value of combining ADMIRE-HF risk score and ERP to predict SCD in HFrEF patients. METHODS: We studied 90 HFrEF outpatients with LVEF< 40% in our prospective cohort study. In cardiac MIBG imaging, the heart-to-mediastinum (H/M) ratio was measured on the delayed planar image. ADMIRE-HF risk score was derived from the sum of the point values of LVEF, H/M ratio, and systolic blood pressure. We also assessed ERP on the standard electrocardiogram. RESULTS: During a median follow-up of 7.5(4.5-12.0) years, 22 patients had SCD. At multivariate Cox analysis, ADMIRE-HF risk score and ERP were independently associated with SCD. Patients with both intermediate/high ADMIRE-HF score and ERP had a higher SCD risk than those with either and none of them. CONCLUSION: The combination of ADMIRE-HF risk score and ERP would provide the incremental prognostic information for predicting SCD in HFrEF patients.

The CHADS2 score predicts ischemic stroke in chronic heart failure patients without atrial fibrillation: comparison to other stroke risk scores.

The CHADS2 score is useful in stratifying the risk of ischemic stroke or transient ischemic attack (TIA) in patients with non-valvular atrial fibrillation (AF). However, it remains unclear whether the CHADS2 score could predict stroke or TIA in chronic heart failure (CHF) patients without AF. Recently, the new stroke risk score was proposed from 2 contemporary heart failure trials. We evaluated the prognostic power of the CHADS2 score for stroke or TIA in CHF patients without AF in comparison to the "stroke risk score". We retrospectively studied 127 CHF patients [left ventricular ejection fraction (LVEF) <40 %] without AF, who had been enrolled in our previous prospective cohort study. The primary endpoint was the incidence of stroke or TIA. The mean baseline CHADS2 score was 2.1 ± 1.0. During the follow-up period of 8.4 ± 5.1 years, stroke or TIA occurred in 21 of 127 patients. At multivariate Cox analysis, CHADS2 score (C-index 0.794), but not "stroke risk score" (C-index 0.625), was significantly and independently associated with stroke or TIA. The incidence of stroke or TIA appeared to increase in relation to the CHADS2 score [low (=1), 0 per 100 person-years; intermediate (=2), 1.6 per 100 person-years; high (≥3), 4.7 per 100 person-years; p = 0.04]. CHADS2 score could stratify the risk of ischemic stroke in CHF patients with the absence of AF, with greater prognostic power than the "stroke risk score".

Risk Stratification for Ventricular Tachyarrhythmias by Ambulatory Electrocardiogram-Based Frequency Domain T-Wave Alternans.

BACKGROUND: Ambulatory electrocardiogram (ECG)-based T-wave alternans (TWA) quantified by the modified moving average method (MMA) can be used to identify patients at risk for sudden cardiac death. However, there is no information available on ambulatory ECG-based TWA as quantified by the frequency domain (FD) method to identify patients with an implantable cardioverter defibrillator (ICD) who are at high risk for ventricular tachyarrhythmias. Further, there are few data regarding the comparison of clinical utility of FD-TWA with MMA-TWA, heart rate variability (HRV), and heart rate turbulence (HRT). METHODS AND RESULTS: In 41 patients with ICD, of whom 14 patients had a past history of at least one appropriate ICD discharge, FD-TWA, MMA-TWA, HRV, and HRT were analyzed from 24-hour Holter ECG monitoring recordings. Only positive results of FD-TWA and abnormal HRV (standard deviation of all normal-to-normal intervals ≤111 ms) were significantly more frequently observed in patients with than without appropriate ICD discharge. Patients with FD-TWA positive had a significantly higher risk of appropriate ICD discharge than those with FD-TWA negative (50% vs 16%; odds ratio, 5.3 [95% confidence interval, 1.2-23.7], P = 0.02). When FD-TWA and HRV were combined, the specificity (93% vs 59%, P = 0.003) and predictive accuracy (83% vs 66%, P = 0.07) for the identification of patients with appropriate ICD discharge were greater than those for FD-TWA only. CONCLUSION: The ambulatory ECG-based FD-TWA might be useful to detect patients with ICD who are at high risk for ventricular tachyarrhythmias, and the combination of FD-TWA and HRV might improve the ability to detect such high-risk patients.

The prognostic impact of follow-up cardiac metaiodobenzylguanidine imaging on left ventricular trajectory after acute decompensation.

AIMS: Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recently, the trajectory of left ventricular ejection fraction (LVEF) has been a focus in patients with reduced LVEF admitted for acute decompensated HF (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 a reduced LVEF of <40%. The cardiac MIBG heart-to-mediastinum ratio (the 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 the 6FUP 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 a composite of readmission for worsening HF and cardiac death. Patients with a lower late HMR at the 6FUP had a greater risk of cardiac events than those with a higher late HMR at the 6FUP 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.

[An autopsy of a case of pulmonary hypertension secondary to pulmonary embolization of intrahepatic cholangiocarcinoma].

A 70-year-old woman was admitted to our hospital for one month because of progressive dyspnea. Her medical history included an operation for hepatolithiasis at age 47. She was a current smoker. Chest CT revealed emphysematous change and honeycombing in the lung and bilateral subpleural opacifications. Cardiac ultrasound examination showed pulmonary hypertension. Treatments with antibiotics, corticosteroids and heparin were unsuccessful. Despite mechanical ventilation, she died of respiratory failure. Autopsy revealed that intrahepatic cholangiocarcinoma had spread via the hematogeneous route, formed multiple emboli into the pulmonary small arteries, and led to severe pulmonary hypertension and lung infarction.

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.

Transcatheter Mitral Valve Edge-to-Edge Repair for Commissure Prolapse Successfully Guided by Stitch Artifact Technique.

Illustration of the "Stitch Artifact Technique". (A) By conducting 2-beat image acquisition without stopping the ventilation, we can create stitch artifact on the 3D image intentionally. (B) This stitch artifact on 3D image indicates the exact position and angle of 2D cut-plane image which we visualized just before showing 3D-image.

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.

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 (

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 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.

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.

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.

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.

Impact of adjunctive tolvaptan on sympathetic activity in acute heart failure with preserved ejection fraction.

AIMS: Acute decompensated heart failure (ADHF) is generally treated by decongestion using diuretic therapy. However, the use of loop diuretics is associated with increased cardiac sympathetic nerve activity (CSNA). We aimed to evaluate the effect of adjunctive tolvaptan therapy on CSNA in ADHF patients with preserved left ventricular ejection fraction (LVEF). METHODS AND RESULTS: We enrolled 51 consecutive ADHF patients with LVEF ≥45%. Patients were randomly assigned to receive either tolvaptan add-on (n = 25) or conventional diuretic therapy (n = 26). Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging was performed after stabilisation of heart failure symptoms, and the cardiac MIBG heart-to-mediastinum ratio (HMR) and washout rate (WR) were calculated. There were no significant differences in the body weight change and total urine volume during 2 days after randomisation or in the HMR on delayed image (HMR(d)) and WR between the tolvaptan and conventional groups. After stratification based on the median change in body weight, the patients with higher weight reduction had a significantly lower HMR(d) (P = 0.0128) and tended to have a higher WR (P = 0.0786) in the conventional group, whereas the cardiac MIBG imaging results were not influenced by body weight reduction in the tolvaptan group. CONCLUSIONS: Adjunctive tolvaptan therapy may provide rapid decongestion without a harmful effect on CSNA in ADHF patients with preserved LVEF.