The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

Not brushing teeth at night may increase the risk of cardiovascular disease.

In this study, we investigated whether toothbrushing timing affects cardiovascular disease risk. We enrolled 1675 patients aged ≥ 20 years who were hospitalized for surgery, examination, or medical treatment. The participants were categorized as follows based on toothbrushing: Group MN (brushing teeth after waking up and at night, n = 409), Group Night (brushing teeth at night but not upon waking up, n = 751), Group M (brushing teeth after waking up but not at night, n = 164), and Group None (not brushing teeth at all, n = 259). The participants' age, sex, smoking history, and follow-up results were evaluated. Group M had four times as many men as women. Multivariate analysis of cardiovascular events showed significantly higher survival estimates in Group MN (P = 0.021) and Group Night (P = 0.004) than in Group None. Kaplan-Meier analysis of subgroups based on smoking status revealed that smokers in Group None had significantly worse prognosis for cardiovascular onset events than smokers in other groups; non-smokers in Groups None and M showed significantly worse prognosis on hospitalization. Our findings are limited to cardiovascular diseases and cannot be generalized to healthy populations. However, we suggest that brushing teeth at night is important for lowering cardiovascular disease risk.

Clinical Efficacy and Safety of Nivolumab in Malignant Non-Pleural Mesothelioma: A Multicenter, Open-Label, Single-Arm, Japanese Phase II Trial (Viola) Protocol.

BACKGROUND: There is no authorized treatment for malignant non-pleural mesothelioma (MNPM) worldwide. In contrast to malignant pleural mesothelioma, MNPM has not been investigated, and no treatment has been established due to its rarity. OBJECTIVES: This multicenter, open-label, single-arm, Japanese phase II trial aims at evaluating the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in advanced or metastatic MNPM treatment. METHODS: This phase II trial commenced in October 2020. Twenty-three patients with advanced or metastatic MNPM who meet the inclusion and exclusion criteria were enrolled from five institutions within 2 years. Regardless of prior therapy, 240 mg of nivolumab will be administered intravenously to MNPM patients every 2 weeks to investigate its efficacy and safety until disease progression or unacceptable toxicities are detected, or the patient's condition meets the withdrawal criteria. RESULTS: The primary endpoint is the objective response rate by central assessment following the Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints include disease control rate, overall survival, progression-free survival, adverse events, and treatment-related adverse events. CONCLUSIONS: This is the first prospective investigator-initiated trial to evaluate the effect of nivolumab monotherapy for MNPM.

Prognostic Impact of Echocardiographic Congestion Grade in HFpEF With and Without Atrial Fibrillation.

Background: Atrial fibrillation (AF) is common in heart failure with preserved ejection fraction (HFpEF). Objectives: This study aimed to investigate the prognostic value of echocardiographic markers of congestion that can be applied to both AF and patients without AF with HFpEF. Methods: We conducted a multicenter study of 505 patients with HFpEF admitted to hospitals for acute decompensated heart failure. The ratio of early diastolic transmitral flow velocity to mitral annulus velocity (E/e'), the tricuspid regurgitation peak velocity, and the collapsibility of the inferior vena cava were obtained at discharge. Congestion was determined by echocardiography if any one of E/e' ≥14 (E/e' ≥11 for AF), tricuspid regurgitation peak velocity ≥2.8 m/s, or inferior vena cava collapsibility <50% was positive. We classified patients into grade A, grade B, and grade C according to the number of positive congestion indices. The primary endpoint was the composite of cardiovascular death and heart failure hospitalization. Results: During the follow-up period (median: 373 days), 162 (32%) patients experienced the primary endpoint. Grade C patients had a higher risk for the primary endpoint than grade A (HR: 2.98; 95% CI: 1.97-4.52) and grade B patients (HR: 1.92; 95% CI: 1.29-2.86) (log-rank P < 0.0001). Echocardiographic congestion grade improved the predictive value when added to the age, sex, New York Heart Association functional class, and N-terminal pro-B-type natriuretic peptide, not only in sinus rhythm (Uno C-statistic: 0.670 vs 0.655) but in AF (Uno C-statistic: 0.667 vs 0.639). Conclusions: Echocardiographic congestion grade has prognostic value in patients with HFpEF with and without AF.

Relationships of Atrial Fibrillation at Diagnosis and Type of Atrial Fibrillation During Follow-up With Long-Term Outcomes for Heart Failure With Preserved Ejection Fraction.

Background: Few data are available regarding the impact of atrial fibrillation (AF) at diagnosis and type of AF during the follow-up period on long-term outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results: In all, 1,697 patients diagnosed as HFpEF between March 2010 and December 2017 were included in this study. At enrollment, 698 (41.1%) patients had AF. Over a median follow-up of 1,017 days, there were no significant differences between patients with and without AF in the adjusted hazard ratio (HR) for all-cause death or admission for heart failure. However, those with AF had a higher risk of stroke (HR 1.831; P=0.003). Of 998 patients with sinus rhythm at enrollment, 139 (13.9%) developed new-onset AF. Predictors of new-onset AF were pulse, hemoglobin, left ventricular end-diastolic dimension, and B-type natriuretic peptide. Compared with sinus rhythm, paroxysmal AF had a similar risk for all-cause death, admission for HF, and stroke; persistent AF had a lower risk of all-cause death (HR 0.701; P=0.015), but a higher risk for admission for HF (HR 1.608; P=0.002); and new-onset AF had a lower risk for all-cause death (HR 0.654; P=0.040), but a higher risk of admission for HF (HR 2.475; P<0.001). Conclusions: In patients with HFpEF, long-term outcome may differ by type of AF. Physicians need to consider individual risk with regard to AF type.

Evolocumab for prevention of microvascular dysfunction in patients undergoing percutaneous coronary intervention: the randomised, open-label EVOCATION trial.

BACKGROUND: Statins have been shown to prevent microvascular dysfunction that may cause periprocedural myocardial infarction after percutaneous coronary intervention (PCI). Evolocumab has more potent lipid-lowering properties than statins.  Aims: The aims of this study were to investigate whether evolocumab pretreatment on top of statin therapy could prevent periprocedural microvascular dysfunction.  Methods: This study included 100 patients with stable coronary artery disease who were scheduled to undergo PCI and had high low-density lipoprotein cholesterol (LDL-C) under statin therapy. Patients were randomised to receive evolocumab 140 mg every 2 weeks for 2 to 6 weeks before PCI (evolocumab group: N=54) or not (control group: N=46). The primary endpoint was the index of microvascular resistance (IMR) after PCI. Troponin T was measured before and 24 hours after PCI.  Results: Geometric mean LDL-C was 94.1 (95% confidence interval [CI]: 86.8-102.1) mg/dl and 89.4 (95% CI: 83.5-95.7) mg/dl at baseline, and 25.6 (95% CI: 21.9-30.0) mg/dl and 79.8 (95% CI: 73.9-86.3) mg/dl before PCI, in the evolocumab group and in the control group, respectively. PCI was performed 22.1±8.5 days after allocation. Geometric mean IMR was 20.6 (95% CI: 17.2-24.6) in the evolocumab group and 20.6 (95% CI: 17.0-25.0) in the control group (p=0.98). There was no significant difference in the geometric mean of post-PCI troponin T (0.054, 95% CI: 0.041-0.071 ng/ml vs 0.054, 95% CI: 0.038-0.077 ng/ml; p=0.99) and in the incidence of major periprocedural myocardial infarction between the 2 groups (44.4% vs 44.2%; p=1.00).  Conclusions: Evolocumab pretreatment did not prevent periprocedural microvascular dysfunction in patients on modern medical management with statins.

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 (

Abdominal obesity, and not general obesity, is associated with a lower 123I MIBG heart-to-mediastinum ratio in heart failure patients with preserved ejection fraction.

BACKGROUND: The relationship between general obesity or abdominal obesity (abdominal circumference of ≥85 cm in men and ≥ 90 cm in women) and the heart-to-mediastinum ratio (HMR), a measure of cardiac sympathetic innervation, on cardiac iodine-123-metaiodobenzylguanidine scintigraphy (MIBG) in patients with heart failure with preserved ejection fraction (HFpEF) has not been clarified. METHODS: A total of 239 HFpEF patients with both MIBG and abdominal circumference data were examined. We divided these patients into those with abdominal obesity and those without it. In the cardiac MIBG study, early phase image was acquired 15-20 min after injection, and late phase image was acquired 3 h after the early phase. A HMR obtained from a low-energy type collimator was converted to that obtained by a medium-energy type collimator. RESULTS: Early and late HMRs were significantly lower in those with abdominal obesity, although washout rates were not significantly different. The incidence of patients with early and late HMRs <2.2 was significantly higher in those with abdominal obesity. Multivariate linear regression analysis revealed that abdominal obesity was independently associated with early HMR (standardized ß = -0.253, P = 0.003) and late HMR (standardized ß = -0.222, P = 0.010). Multivariate logistic regression analysis revealed that abdominal obesity was independently associated with early (odds ratio [OR] [95% confidence interval {CI}] = 4.25 [2.13, 8.47], P < 0.001) and late HMR < 2.2 (OR [95% CI] = 2.06 [1.11, 3.83], P = 0.022). Elevated BMI was not significantly associated with low early and late HMR. The presence of abdominal obesity was significantly associated with low early and late HMR even in patients without elevated BMI values. CONCLUSION: Abdominal obesity, but not general obesity, in HFpEF patients was independently associated with low HMR, suggesting that visceral fat may contribute to decreased cardiac sympathetic activity in patients with HFpEF. TRIAL REGISTRATION: UMIN000021831.

Prognostic significance of intra-aortic balloon pumping support in patients with acute myocardial infarction and veno-arterial extracorporeal membrane oxygenation therapy.

BACKGROUND: The prognostic significance of combining intra-aortic balloon pumping (IABP) with extracorporeal membrane oxygenation (ECMO) for acute myocardial infarction (AMI) patients is still unclear. We investigated whether combining IABP with veno-arterial (VA)-ECMO is associated with a lower risk of short-term mortality. METHODS: Among 12,093 AMI cases enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS), we identified 519 who were administered VA-ECMO during hospitalization. Among these, 459 received IABP support (IABP group) and 60 cases did not (no-IABP group). The primary endpoint was 30-day all-cause death; the secondary endpoint was major bleeding. Logistic regression analysis using original data was conducted. We also established weighted logistic regression models with inverse probability of treatment weighting (IPTW). RESULTS: Logistic regression analysis revealed that IABP use was significantly associated with a reduced risk of 30-day death in the original data [odds ratio (OR) 0.504, 95% confidence interval (CI) 0.282-0.901, p = 0.021]. After IPTW-adjustment for clinically relevant covariates with the use of IABP, patients receiving VA-ECMO with IABP had a lower risk of 30-day death (OR 0.816, 95% CI 0.746-0.892, p < 0.001) compared to those without IABP. The incidence of major bleeding was comparable between the groups (IABP 29.0% vs. non-IABP 21.7%, p=0.302). However, the risk of major bleeding was higher in the IABP group after IPTW-adjustment (OR 1.092, 95% CI 1.008-1.184, p=0.032). CONCLUSIONS: IABP support for AMI patients with VA-ECMO was significantly associated with reduced risk of short-term mortality, suggesting that the addition of IABP support might contribute to improved survival in AMI patients requiring VA-ECMO.

Factors Associated With Prehospital Delay Among Patients With Acute Myocardial Infarction in the Era of Percutaneous Coronary Intervention　- Insights From the OACIS Registry.

BACKGROUND: The Japan Circulation Society launched the STOP-MI campaign in 2014, focusing on immediate hospital arrival for acute myocardial infarction (AMI) treatment. This study aimed to determine the factors influencing longer prehospital time among patients with AMI in Japan.Methods and Results:This study analyzed a total of 4,625 AMI patients enrolled in the Osaka Acute Coronary Insufficiency Study registry from 1998 to 2014. The prehospital time delay was defined as the time interval from the onset of initial symptoms to hospital arrival time ≥2 h. Among eligible patients, 2,927 (63.3%) had a prehospital time ≥2 h. In multivariable analyses, age 65-79 years (adjusted odds ratio [AOR] 1.19, 95% confidence interval [CI] 1.02-1.39), age ≥80 years (AOR 1.42, 95% CI 1.13-1.79), diabetes mellitus (AOR 1.33, 95% CI 1.16-1.52), and onset time of 0:00-5:59 h (AOR 1.63, 95% CI 1.37-1.95) were positively associated with prehospital time ≥2 h, whereas smoking (AOR 0.78, 95% CI 0.68-0.90) and ambulance use (AOR 0.37, 95% CI 0.32-0.43) were negatively associated with prehospital time ≥2 h. CONCLUSIONS: Older age, diabetes mellitus, and nighttime onset were associated with prehospital time delay for AMI patients, whereas smoking and ambulance use were associated with no prehospital time delay. Healthcare providers and patients could help reduce the time to get to a medical facility by being aware of these findings.

Manual Thrombus Aspiration and its Procedural Stroke Risk in Myocardial Infarction.

Background The previous large-scale randomized controlled trial showed that routine thrombus aspiration (TA) during percutaneous coronary intervention (PCI) was associated with an increased risk of stroke. However, real-world clinical evidence is still limited. Methods and Results We investigated the association between manual TA and stroke risk during primary PCI in the OACIS (Osaka Acute Coronary Insufficiency Study) database (N=12 093). The OACIS is a prospective, multicenter registry of myocardial infarction. The primary end point of the present study is stroke at 7 days. A total of 9147 patients who underwent primary PCI within 24 hours of hospitalization were finally analyzed (TA group, n=4448, versus non-TA group, n=4699 patients). TA was independently associated with risk of stroke at 7 days (odds ratio [OR], 1.92 [95% CI, 1.19‒3.12]; P=0.008) in the simple logistic regression model, while the multilevel random effects logistic regression model with hospital treated as a random effect showed that manual TA was not associated with incremental risk of stroke at 7 days (OR, 0.91 [95% CI, 0.71‒1.16]; P=0.435). The 7-day stroke risk of manual TA was significantly heterogeneous in different institutions (Pfor interaction=0.007). Conclusions Manual TA during primary PCI for patients with acute myocardial infarction was independently associated with the overall increased risk of periprocedural stroke. However, this result was substantially skewed because of institution specific risk variation, suggesting that the periprocedural stroke may be preventable by prudent PCI procedure or appropriate periprocedural management. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000005464. Unique identifier: UMIN000004575.

Prognostic significance of dipstick proteinuria in heart failure with preserved ejection fraction: insight from the PURSUIT-HFpEF registry.

OBJECTIVE: The semiquantitative urine dipstick test is a simple and convenient method that is available in the smallest community-based healthcare clinics. We sought to clarify the prognostic significance of dipstick proteinuria in patients with heart failure (HF) with preserved ejection fraction (HFpEF). DESIGN: A Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) registry. PARTICIPANTS AND SETTING: We assessed 851 discharged-alive patients in the PURSUIT-HFpEF registry who were initially hospitalised due to an acute decompensated HFpEF (EF≥50%) and elevated N-terminal-pro-brain natriuretic peptide (≥400 ng/L) at Osaka University Hospital and other 30 affiliated hospitals in the Kansai region of Japan. Patients received a urine dipstick test, and were divided into two groups according to the absence or presence of proteinuria. A trace or more of dipstick proteinuria was defined as the presence of proteinuria. MAIN OUTCOME MEASURES: A composite of cardiac death or HF rehospitalisation. RESULTS: Median age was 83 years and 473 patients (55.6%) were female. Five hundred and two patients (59%) were proteinuria (-) and 349 patients (41%) were proteinuria (+). The composite endpoint and HF rehospitalisation occurred more often in proteinuria (+) individuals than proteinuria (-) individuals (log-rank p=0.006 and p=0.007, respectively); but cardiac death did not (log-rank p=0.139). Multivariable Cox regression analysis showed that the presence of proteinuria was associated with the composite endpoint (HR: 1.47, 95% CI 1.07 to 2.01, p=0.016), and HF rehospitalisation (HR: 1.48, 95% CI 1.07 to 2.05, p=0.020), but not with cardiac death (HR: 1.52, 95% CI 0.83 to 2.76, p=0.172). CONCLUSIONS: Dipstick proteinuria may be a prognostic marker in patients with HFpEF. Evaluation of proteinuria by a urine dipstick test may be a simple but useful method for risk stratification in HFpEF. UMIN-CTR ID: UMIN000021831.

Prognostic Impact of Echocardiographic Diastolic Dysfunction on Outcomes in Patients With Heart Failure With Preserved Ejection Fraction　- Insights From the PURSUIT-HFpEF Registry.

BACKGROUND: Although diastolic dysfunction is important pathophysiology in heart failure with preserved ejection fraction (HFpEF), its prognostic impact in HFpEF patients, including those with atrial fibrillation (AF), remains to be elucidated.Methods and Results:We included the data for 863 patients (321 patients with AF) registered in a prospective multicenter observational study of patients with HFpEF. Patients were divided into 3 groups according to the 2016 ASE/EACVI recommendations. The primary endpoint was a composite of all-cause death or HF rehospitalization. Median age was 83 years, and 55.5% were female. 196 (22.7%) were classified with normal diastolic function (ND), 253 (29.3%) with indeterminate (ID) and 414 (48.0%) with diastolic dysfunction (DD). The primary endpoint occurred more frequently in patients with DD than in those with ND or ID (log-rank P<0.001 for DD vs. ND, and log-rank P=0.007 for DD vs. ID, respectively). Taking ND as the reference, multivariable Cox regression analysis revealed that DD (hazard ratio (HR): 1.57, 95% confidence interval (CI):1.06-2.32, P=0.024) was independently associated with the composite endpoint, whereas ID (HR: 1.28, 95% CI: 0.84-1.95, P=0.255) was not. DD was associated with the composite endpoint in both patients with and without AF. CONCLUSIONS: HFpEF patients classified with DD using the 2016 ASE/EACVI recommendations had worse clinical outcomes than those with ND or ID. DD may be considered a prognostic marker in patients with HFpEF regardless of AF.

The efficacy and safety of left atrial low-voltage area guided ablation for recurrence prevention compared to pulmonary vein isolation alone in patients with persistent atrial fibrillation trial: Design and rationale.

Recurrence rates of atrial fibrillation (AF) after pulmonary vein isolation (PVI) are higher in patients with a left atrial low-voltage area (LVA) than those without. However, the efficacy of LVA guided ablation is still unknown. The purpose of this study-the Efficacy and Safety of Left Atrial Low-voltage Area Guided Ablation for Recurrence Prevention Compared to Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation trial (SUPPRESS-AF trial)-is to elucidate whether LVA guided ablation in addition to PVI is superior to PVI alone in patients with persistent AF. The Osaka Cardiovascular Conference will conduct a multicenter, randomized, open-label trial aiming to examine whether LVA guided ablation in addition to PVI is superior to PVI alone in patients with persistent AF and LVAs. The primary outcome is the recurrence of AF documented by scheduled or symptom-driven electrocardiography (ECG) during the 1 year follow-up period after the index ablation. The key secondary endpoints include all-cause death, symptomatic stroke, bleeding events, and other complications related to the procedure. A total of 340 patients with an LVA will be enrolled and followed up to 1 year. The SUPPRESS-AF trial is a randomized controlled trial designed to assess whether LVA guided ablation in addition to PVI is superior to PVI alone for patients with persistent AF and LVAs detected while undergoing their first catheter ablation.

Prognostic impact of Clinical Frailty Scale in patients with heart failure with preserved ejection fraction.

AIMS: Frailty is associated with prognosis of cardiovascular diseases. However, the significance of frailty in patients with heart failure with preserved ejection fraction (HFpEF) remains to be elucidated. The purpose of this study was to examine the prognostic significance of the Clinical Frailty Scale (CFS) in real-world patients with HFpEF using data from a prospective multicentre observational study of patients with HFpEF (PURSUIT-HFpEF study). METHOD AND RESULTS: We classified 842 patients with HFpEF enrolled in the PURSUIT-HFpEF study into two groups using CFS. The registry enrolled patients hospitalized with a diagnosis of decompensated heart failure. Median age was 82 [interquartile range: 77, 87], and 45% of the patients were male. Of 842 patients, 406 were classified as high CFS (CFS ≥ 4, 48%) and 436 as low CFS (CFS ≤ 3, 52%). The primary endpoint was the composite of all-cause mortality and heart failure admission. Secondary endpoints were all-cause mortality and heart failure admission. Patients with high CFS were older (85 vs. 79 years, P < 0.001), predominantly female (65% vs. 46%, P < 0.001) and more likely to have New York Heart Association (NYHA) ≥ 2 (75% vs. 53%, P < 0.001) and a higher level of NT-proBNP (1360 vs 838 pg/mL, P < 0.001) than those with low CFS. Patients with high CFS had a significantly greater risk of composite endpoint (Kaplan-Meier estimated 1-year event rate 39% vs. 23%, log-rank P < 0.001), all-cause mortality (Kaplan-Meier estimated 1-year event rate 17% vs. 7%, log-rank P < 0.001) and heart failure admission (Kaplan-Meier estimated 1-year event rate 28% vs. 19%, log-rank P = 0.002) than those with low CFS. Multivariable Cox regression analysis revealed that high CFS was significantly associated with composite endpoint (adjusted HR 1.92, 95% CI 1.35-2.73, P < 0.001), all-cause mortality (adjusted HR 2.54, 95% CI 1.39-4.66, P = 0.003) and heart failure admission (adjusted HR 1.55, 95% CI 1.03-2.32, P = 0.035) even after adjustment for covariates. Moreover, change in CFS grade was also significantly associated with composite endpoint (adjusted HR 1.23, 95% CI 1.11-1.36, P < 0.001), all-cause mortality (adjusted HR 1.32, 95% CI 1.13-1.55, P = 0.001) and heart failure admission (adjusted HR 1.15, 95% CI 1.02-1.30, P = 0.021). CONCLUSIONS: Frailty assessed by the CFS was associated with poor prognosis in patients with HFpEF.

High density lipoprotein cholesterol / C reactive protein ratio in heart failure with preserved ejection fraction.

AIMS: The impacts of high density lipoprotein cholesterol (HDL-C) as an anti-inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At present, the clinical significance of the HDL-C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. METHODS AND RESULTS: We examined the data on 796 consecutive HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT-HFpEF registry, a prospective, multicentre observational study. We calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow-up duration was 420 ± 346 days. All-cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all-cause death (odds ratio = 1.84, 95% CI: 1.06-3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36-6.01, P = 0.003). HDL-C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta-coefficient = -0.085, P = 0.034 and standardized beta-coefficient = 0.081, P = 0.044, respectively). CONCLUSIONS: HDL-C/CRP ratio was a useful marker for predicting all-cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.

Prevalence of the Japanese high bleeding risk criteria and its prognostic significance for fatal bleeding in patients with acute myocardial infarction.

BACKGROUND: The Japanese high-bleeding-risk criteria (Japanese-HBR), modified criteria of the Academic Research Consortium (ARC) HBR, has been recently proposed. We aimed to investigate the prevalence of the ARC-HBR and the Japanese-HBR, and to assess their prognostic significance in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: We applied the ARC-HBR and the Japanese-HBR criteria to the OACIS prospective multicenter acute myocardial infarction registry (12,093 patients, 66 ± 12 years, 9,096 males). The primary endpoint was fatal bleeding (BARC-5). Median follow-up duration was 4.84 [inter-quartile range 1.35, 5.01] years. Prevalence of the ARC-HBR was 43.8%, while that of the Japanese-HBR was 61.8%. Cumulative incidence of fatal bleeding was higher in the ARC-HBR group than in the no ARC-HBR group at 1 year (1.3 vs. 0.6%) and at 5 years (2.0 vs. 0.7%). The Kaplan-Meier curves stratified by the Japanese-HBR criteria more prominently diverged (1.3 vs. 0.2% at 1 year; and 1.9 vs. 0.3% at 5 years). The Japanese-HBR criteria showed superior discriminative performance over the ARC-HBR criteria (C-statistics: 0.677 vs. 0.598, P < 0.001). CONCLUSIONS: In the real-world Japanese AMI registry, nearly half of the patients fulfilled the criteria of ARC-HBR, and two-thirds met the Japanese-HBR. Our findings support the validity of both ARC- and Japanese-HBR criteria in AMI patients but encourage the future application of the Japanese-HBR criteria to the Japanese AMI cohort. TRIAL REGISTRATION NUMBER: UMIN000004575.

Impact of readmissions on octogenarians with heart failure with preserved ejection fraction: PURSUIT-HFpEF registry.

AIMS: Heart failure (HF) readmissions with preserved ejection fraction (HFpEF) are increasing in the elderly, which is a major socioeconomic problem. We investigated the clinical impact of HF readmissions (HFR) on octogenarians with HFpEF. METHODS AND RESULTS: We enrolled consecutive octogenarians (≥80 years old) from June 2016 to February 2020 in PURSUIT-HFpEF registry. We divided them into HFR group readmitted for HF during the follow-up period and non-HF readmission (non-HFR) group. We evaluated the impact of HFR on all-cause mortality, cardiac death, and quality of life (QOL). Additionally, we evaluated the factors at discharge correlated with HFR. HFR group comprised 116 patients (21.4%). Among all-cause deaths, 40 patients suffered cardiac deaths (48.2%). The Kaplan-Meier analysis revealed a similar prognosis between HFR and non-HFR groups as well as similar incidences of HF deaths. The QOL scores had significantly deteriorated by 1 year later in the HFR group (0.71 ± 0.19 vs. 0.59 ± 0.21, P < 0.001), while it was similar at 1 year in the non-HFR group. In the multivariate analysis, diabetes mellitus (DM) (P = 0.019), N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels ≥ 1611 pg/mL (P < 0.001), and serum albumin level ≤ 3.7 g/dL (P = 0.011) were useful markers for HFR in octogenarians. CONCLUSIONS: In octogenarians with HFpEF, HF readmission was not directly correlated with the prognosis but was well correlated with the QOL. Close follow-up is essential to decrease HFR of octogenarians with HFpEF with DM, high NT-pro BNP (≥1611 pg/mL) and low albumin (≤3.7 g/dL) levels at discharge.

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.

Population-specific and trans-ancestry genome-wide analyses identify distinct and shared genetic risk loci for coronary artery disease.

To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.