Overview of the 87th Annual Scientific Meeting of the Japanese Circulation Society (JCS2023)　- New Challenge With Next Generation.

The 87thAnnual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

Evaluation of the A2B Score for Prediction of Survival in Patients With Heart Failure in a Nationwide Cohort in Japan.

BACKGROUND: Although a tool for sharing patient prognosis among all medical staff is desirable in heart failure (HF) cases, only a few simple HF prognostic scores are available. We previously presented the A2B score, a simple user-friendly HF risk score, and validated it in a small single-center cohort. In the present study, we validated it in a larger nationwide cohort. METHODS AND RESULTS: We examined the 2-year mortality in relation to the A2B scores in 3483 patients from a Japanese nationwide cohort and attempted to stratify their prognoses according to the scores. The A2B score was determined by assigning points for age, anemia, and brain natriuretic peptide (BNP) level at discharge: age (<65 years, 0; 65-74 years, 1; ≥75 years, 2), anemia (hemoglobin ≥12 g/dL, 0; 10-11.9 g/dL, 1; <10 g/dL, 2), and BNP (<200 pg/mL, 0; 200-499 pg/mL, 1; ≥500 pg/mL, 2). Hemoglobin and BNP levels were applied to the data at discharge. The 2-year survival rates for A2B scores 1, 2, 3, 4, 5, and 6 were 94.1%, 83.2%, 74.1%, 63.5%, 51.6%, and 41.5%, respectively; the mortality rate increased by ≈10% for each point increase (c-index, 0.702). The A2B score was applicable in HF cases with reduced or preserved ejection fraction and remained useful when BNP was substituted with N-terminal proBNP (c-index, 0.749, 0.676, and 0.682, respectively). CONCLUSIONS: The A2B score showed a good prognostic value for HF in a large population even when BNP was replaced with N-terminal proBNP.

Atrial fibrillation type and long-term clinical outcomes in hospitalized patients with heart failure: insight from JROADHF.

AIMS: Atrial fibrillation (AF) type (paroxysmal, persistent, or permanent) is important in determining therapeutic management; however, clinical outcomes by AF type are largely unknown for hospitalized patients with heart failure (HF). METHODS AND RESULTS: The Japanese Registry Of Acute Decompensated Heart Failure is a retrospective, multicenter, and nationwide registry of patients hospitalized for acute HF in Japan. Follow-up data were collected up to 5 years after hospitalization. Patients were divided based on diagnosis and AF type into 3 groups [without AF, paroxysmal AF, and sustained AF (defined as a composite of persistent and permanent AF)], and compared the backgrounds and outcomes between the groups. Of 12 895 hospitalized HF patients [mean age: 78 ± 13 years, female: 6077 (47%), and mean left ventricular ejection fraction: 47 ± 17%], 1725 had paroxysmal AF, and 3672 had sustained AF. Compared with patients without AF, sustained AF had a higher risk of the primary composite endpoint of cardiovascular (CV) death or HF hospitalization [hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.01-1.17; P = 0.03], mainly driven by HF hospitalization [HR: 1.16, 95% CI: 1.06-1.26; P < 0.001], whereas the corresponding risk for the primary endpoint in patients with paroxysmal AF was not elevated (HR: 1.03, 95% CI: 0.94-1.13; P = 0.53) after adjustment by multivariable Cox regression analysis. These results were consistent among the subgroups of patients with reduced or preserved ejection fraction (interaction P = 0.74). CONCLUSION: Among hospitalized patients with HF, sustained AF, but not paroxysmal AF, was significantly associated with a higher risk for CV death or HF hospitalization, indicating the importance of accounting for AF type in HF patients.

Association of baseline electrocardiographic left ventricular hypertrophy with future renal function decline in the general population.

Electrocardiographic left ventricular hypertrophy (LVH) could predict adverse renal outcomes in patients with hypertension. This study aimed to investigate the association between electrocardiographic LVH and future decline in renal function in the general population using a dataset of population-based health checkups from 2010 to 2019 including 19,825 participants. Electrocardiographic LVH was defined according to the Minnesota code. Renal function decline was defined as a decrease of ≥ 25% in the estimated glomerular filtration rate from baseline to < 60 mL/min/1.73 m2. Electrocardiographic LVH was found in 1263 participants at the baseline visit. The mean follow-up period was 3.4 ± 1.9 years. The incidence rates of renal function decline were 0.30 and 0.78 per 100 person-years in the non-LVH group and LVH groups, respectively. Electrocardiographic LVH was associated with the risk for renal function decline in the adjusted analysis (hazard ratio 1.69, 95% confidence interval 1.14-2.50, P = 0.009). This association was comparable across subgroups stratified by age, sex, body mass index, diagnosed hypertension, systolic blood pressure, hemoglobin A1c, and urinary protein. This study underscores the usefulness of electrocardiographic LVH to detect high-risk individuals for renal function decline in the setting of health checkups in the general population.

Development of deep-learning models for real-time anaerobic threshold and peak VO2 prediction during cardiopulmonary exercise testing.

AIMS: Exercise intolerance is a clinical feature of patients with heart failure (HF). Cardiopulmonary exercise testing (CPET) is the first-line examination for assessing exercise capacity in patients with HF. However, the need for extensive experience in assessing anaerobic threshold (AT) and the potential risk associated with the excessive exercise load when measuring peak oxygen uptake (peak VO2) limit the utility of CPET. This study aimed to use deep-learning approaches to identify AT in real time during testing (defined as real-time AT) and to predict peak VO2 at real-time AT. METHODS AND RESULTS: This study included the time-series data of CPET recorded at the Department of Cardiovascular Medicine, Kyushu University Hospital. Two deep neural network models were developed to: (i) estimate the AT probability using breath-by-breath data and (ii) predict peak VO2 using the data at the real-time AT. The eligible CPET contained 1472 records of 1053 participants aged 18-90 years and 20% were used for model evaluation. The developed model identified real-time AT with 0.82 for correlation coefficient (Corr) and 1.20 mL/kg/min for mean absolute error (MAE), and the corresponding AT time with 0.86 for Corr and 0.66 min for MAE. The peak VO2 prediction model achieved 0.87 for Corr and 2.25 mL/kg/min for MAE. CONCLUSION: Deep-learning models for real-time CPET analysis can accurately identify AT and predict peak VO2. The developed models can be a competent assistant system to assess a patient's condition in real time, expanding CPET utility.

Cardiopulmonary exercise testing can be used to evaluate the condition of patients with heart failure during exercise. Developed deep-learning models can accurately predict a patient's anaerobic threshold in real time and peak oxygen uptake. The models can be used by clinicians for more objective and accurate assessments in real time, expanding the utility of cardiopulmonary exercise testing.

Mapping of Purkinje-related ventricular arrhythmias by a multispline catheter with small and close-paired electrodes: Comparison with conventional catheters.

BACKGROUND: Precise mapping of the Purkinje fiber network is essential in catheter ablation of Purkinje-related ventricular arrhythmias (PrVAs). We sought to evaluate the mapping ability of a multi-spline duodecapolar catheter (PentaRay) for PrVAs. METHODS: Mappings of Purkinje fibers by PentaRay catheters were compared with those by conventional mapping catheters in consecutive patients undergoing catheter ablation of PrVAs from 2015 to 2022. RESULTS: Sixteen PrVAs (7 premature ventricular contractions or non-reentrant fascicular tachycardias [PVCs/NRFTs] and 9 fascicular ventricular tachycardias [FVTs]) were retrospectively studied. In PVCs/NRFTs, earliest preceding Purkinje potentials (PPs) could be recorded by the PentaRay catheters but not by the mapping and ablation catheters in 5 cases. At the earliest PP sites, the precedence from the QRS onset was greater, and the amplitude of the preceding potentials was higher in the PentaRay catheter compared with those in the mapping and ablation catheter (-62.0 ± 42.8 vs. -29.4 ± 34.2 ms, P = 0.02; 0.45 ± 0.43 vs. 0.09 ± 0.08 mV, P = 0.02). In FVTs, late diastolic potentials (P1) were recorded by the PentaRay catheters but not by the mapping and ablation catheters or the linear duodecapolar catheter in 2 cases. The amplitude of P1 was higher in the PentaRay catheter compared with that in the linear duodecapolar catheter and the mapping and ablation catheters (0.72 ± 0.49 vs. 0.17 ± 0.18 vs. 0.27 ± 0.21 mV, P = 0.0006, P = 0.002). The localized critical PPs, defined as the earliest preceding potentials in PVCs/NRFTs and P1 in FVTs, could be recorded in all the patients by the PentaRay catheter. The mapping ability of critical PPs of PrVAs was better with the PentaRay catheter than with the conventional mapping catheters (16/16 vs. 9/16, P = 0.004 by McNemar exact test). CONCLUSIONS: The PentaRay catheter has clinical advantages in mapping of the Purkinje fiber network to reveal critical PPs as ablation targets of PrVAs.

Cardiac Autoantibodies Against Cardiac Troponin I in Post-Myocardial Infarction Heart Failure: Evaluation in a Novel Murine Model and Applications in Therapeutics.

BACKGROUND: Cardiac autoantibodies (cAAbs) are involved in the progression of adverse cardiac remodeling in heart failure (HF). However, our understanding of cAAbs in HF is limited owing to the absence of relevant animal models. Herein, we aimed to establish and characterize a murine model of cAAb-positive HF after myocardial infarction (MI), thereby facilitating the development of therapeutics targeting cAAbs in post-MI HF. METHODS: MI was induced in BALB/c mice. Plasma cAAbs were evaluated using modified Western blot-based methods. Prognosis, cardiac function, inflammation, and fibrosis were compared between cAAb-positive and cAAb-negative MI mice. Rapamycin was used to inhibit cAAb production. RESULTS: Common cAAbs in BALB/c MI mice targeted cTnI (cardiac troponin I). Herein, 71% (24/34) and 44% (12/27) of the male and female MI mice, respectively, were positive for cAAbs against cTnI (cTnIAAb). Germinal centers were formed in the spleens and mediastinal lymph nodes of cTnIAAb-positive MI mice. cTnIAAb-positive MI mice showed progressive cardiac remodeling with a worse prognosis (P=0.014, by log-rank test), which was accompanied by cardiac inflammation, compared with that in cTnIAAb-negative MI mice. Rapamycin treatment during the first 7 days after MI suppressed cTnIAAb production (cTnIAAb positivity, 59% [29/49] and 7% [2/28] in MI mice treated with vehicle and rapamycin, respectively; P<0.001, by Pearson χ2 test), consequently improving the survival and ameliorating cardiac inflammation, cardiac remodeling, and HF in MI mice. CONCLUSIONS: The present post-MI HF model may accelerate our understanding of cTnIAAb and support the development of therapeutics against cTnIAAbs in post-MI HF.

Efficacy of Early Catheter Ablation for Atrial Fibrillation After Admission for Heart Failure.

BACKGROUND: Advances in catheter ablation (CA) for atrial fibrillation (AF) have improved the prognosis of patients with heart failure (HF) and AF. However, its optimal timing remains to be fully elucidated. OBJECTIVES: The aim of this study was to investigate the prognostic impact of early CA in patients with HF and AF hospitalized for worsening HF. METHODS: From JROADHF (Japanese Registry of Acute Decompensated Heart Failure) (n = 13,238), patients with HF and AF who underwent CA within 90 days after admission for HF (early CA; n = 103) and those who did not (control; n = 2,683) were identified. Mortality was compared between these groups in the crude cohort, as well as in the propensity-matched cohort (n = 83 in each group). RESULTS: In the crude cohort, all-cause mortality was significantly lower in the early CA group than in the control group (log-rank P < 0.001; HR: 0.38; 95% CI: 0.24-0.60). In the matched cohort, all-cause mortality was likewise significantly lower in the early CA group (log-rank P = 0.014; HR: 0.47; 95% CI: 0.25-0.88). Cardiovascular death and HF mortality were significantly lower in both cohorts (crude: Gray' test: P < 0.001 and P = 0.005; subdistribution HR: 0.28 [95% CI: 0.13-0.63] and HR: 0.31 [95% CI: 0.13-0.75]; matched: Gray's test: P = 0.006 and P = 0.017; subdistribution HR: 0.24 [95% CI: 0.08-0.70] and HR: 0.28 [95% CI: 0.09-0.84], respectively). CONCLUSIONS: In a nationwide representative real-world cohort, CA for AF within 90 days after admission for HF was associated with improved long-term outcomes, including cardiovascular and HF death in patients with HF and AF.

Prevalence, characteristics and cardiovascular and non-cardiovascular outcomes in patients with heart failure with supra-normal ejection fraction: Insight from the JROADHF study.

AIMS: We aimed to investigate the characteristics and prognosis of patients with heart failure (HF) with supra-normal ejection fraction (HFsnEF) compared to HF with normal ejection fraction (HFnEF). METHODS AND RESULTS: Among 11 573 patients enrolled in the nationwide registry of hospitalized patients with HF in Japan, 1943 patients (16.8%) were classified as HFsnEF (left ventricular ejection fraction [LVEF] >65%), 3277 (28.3%) as HFnEF (50% ≤ LVEF ≤65%), 2024 (17.5%) as HF with mildly reduced ejection fraction (40% ≤ LVEF <50%) and 4329 (37.4%) as HF with reduced ejection fraction (LVEF <40%). Patients with HFsnEF were older, more likely to be women, had lower natriuretic peptide values, and had smaller left ventricles than those with HFnEF. The primary endpoint, the composite of cardiovascular death or HF readmission, did not differ between HFsnEF (802/1943, 41.3%) and HFnEF (1413/3277, 43.1%) during a median follow-up period of 870 days (hazard ratio [HR] 0.96, 95% confidence interval 0.88-1.05, p = 0.346). The incidence of secondary outcomes, including all-cause, cardiovascular, and non-cardiovascular deaths and HF readmission, did not differ between HFsnEF and HFnEF. In the multivariable Cox regression analysis, HFsnEF compared to HFnEF was associated with a lower adjusted HR for HF readmission but not with the primary and other secondary endpoints. HFsnEF was associated with a higher HR for the composite endpoint and all-cause death in women, and a higher HR for all-cause death in patients with renal dysfunction. CONCLUSIONS: Heart failure with supra-normal ejection fraction is a common and distinctive phenotype, and has different characteristics and prognoses from HFnEF.

Propensity-Matched Study of Early Cardiac Rehabilitation in Patients With Acute Decompensated Heart Failure.

BACKGROUND: The impact of early implementation of cardiac rehabilitation (CR) in heart failure (HF) patients remains to be elucidated. This study sought to determine whether CR during HF hospitalization could improve prognostic outcomes in patients with acute decompensated HF. METHODS: We analyzed patients with HF enrolled in the JROADHF (Japanese Registry of Acute Decompensated Heart Failure) registry, a retrospective, multicenter, nationwide registry of patients hospitalized for acute decompensated HF. Eligible patients were divided into 2 groups according to CR during hospitalization. The primary outcome was a composite of cardiovascular death or rehospitalization due to cardiovascular event after discharge. The secondary outcomes were cardiovascular death and cardiovascular event rehospitalization. RESULTS: Out of 10 473 eligible patients, 3210 patients underwent CR. Propensity score matching yielded 2804 pairs. Mean age was 77±12 years and 3127 (55.8%) were male. During a mean follow-up of 2.8 years, the CR group had lower incidence rates of the composite outcome (291 versus 327 events per 1000 patient-years; rate ratio, 0.890 [95% CI, 0.830-0.954]; P=0.001) and rehospitalization due to cardiovascular event (262 versus 295 events per 1000 patient-years; rate ratio, 0.888 [95% CI, 0.825-0.956]; P=0.002) than the no CR group. In-hospital CR was associated with an improvement in Barthel index for activities of daily living (P=0.002). Patients with very low Barthel index at admission were benefited by CR in comparison with patients with independent Barthel index (very low; hazard ratio, 0.834 [95% CI, 0.742-0.938]: independent; hazard ratio, 0.985 [95% CI, 0.891-1.088]; P for interaction=0.035). CONCLUSIONS: CR implementation during hospitalization was associated with better long-term outcomes in patients with acute decompensated HF. These data support the need for a randomized, controlled, adequately powered trial to definitively test the role of early physical rehabilitation in hospitalized patients with HF.

Regional Variation in the Clinical Practice and Prognosis in Patients With Heart Failure With Reduced Ejection Fraction in Japan　- A Report From the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).

BACKGROUND: The present study aimed to clarify the regional variations in clinical practice and the prognosis of patients with heart failure with reduced ejection fraction (HFrEF) in Japan using the Japanese Registry of Acute Decompensated Heart Failure (JROADHF).Methods and Results: We recruited data of hospitalized patients with HFrEF (n=4,329) from the JROADHF. The patients were divided into 6 groups based on the region of Japan where they were hospitalized: Hokkaido-Tohoku (n=504), Kanto (n=958), Chubu (n=779), Kinki (n=902), Chugoku-Shikoku (n=446), and Kyushu (n=740). We compared the patients' characteristics, including etiology of HF and prognosis after discharge. The age of the patients was lowest in the Kanto and Kinki regions. In contrast, there were no differences in the prevalence of comorbidities, levels of B-type natriuretic peptide, or left ventricular EF among the 6 groups. Post-discharge cardiospecific prognosis, specifically, the composite of cardiac death or HF hospitalization, cardiac death, and HF hospitalization, was comparable among the 6 regions. CONCLUSIONS: There were no differences in cardiospecific prognosis in patients with HFrEF among the 6 regions in Japan.

Beneficial Effects of Dipeptidyl Peptidase-4 Inhibitors on Heart Failure With Preserved Ejection Fraction and Diabetes.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to exert pleiotropic effects on heart failure (HF) in animal experiments. Objectives: This study sought to investigate the impact of DPP-4 inhibitors on HF patients with diabetes mellitus (DM). Methods: We analyzed hospitalized patients with HF and DM enrolled in the JROADHF (Japanese Registry Of Acute Decompensated Heart Failure) registry, a nationwide registry of acute decompensated HF. Primary exposure was the use of a DPP-4 inhibitor. The primary outcome was a composite of cardiovascular death or HF hospitalization during the median follow-up of 3.6 years according to left ventricular ejection fraction. Results: Out of 2,999 eligible patients, 1,130 had heart failure with preserved ejection fraction (HFpEF), 572 had heart failure with midrange ejection fraction (HFmrEF), and 1,297 had heart failure with reduced ejection fraction (HFrEF). In each cohort, 444, 232, and 574 patients received a DPP-4 inhibitor, respectively. A multivariable Cox regression model showed that DPP-4 inhibitor use was associated with a lower composite of cardiovascular death or HF hospitalization in HFpEF (HR: 0.69; 95% CI: 0.55-0.87; P = 0.002) but not in HFmrEF and HFrEF. Restricted cubic spline analysis demonstrated that DPP-4 inhibitors were beneficial in patients with higher left ventricular ejection fraction. In HFpEF cohort, propensity score matching yielded 263 pairs. DPP-4 inhibitor use was associated with a lower incidence rate of the composite of cardiovascular death or HF hospitalization (19.2 vs 25.9 events per 100 patient-years; rate ratio: 0.74; 95% CI: 0.57-0.97; P = 0.027) in matched patients. Conclusions: DPP-4 inhibitor use was associated with better long-term outcomes in HFpEF patients with DM.

A higher resting heart rate is associated with cardiovascular event risk in patients with type 2 diabetes mellitus without known cardiovascular disease.

A higher resting heart rate (RHR) is associated with an increased risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The aim of this study was to investigate the association between RHR and cardiovascular events in T2DM patients with diabetic retinopathy and without known cardiovascular disease. We analyzed the association between RHR and cardiovascular events, including coronary, cerebral, renal and vascular events or cardiovascular death in T2DM patients with retinopathy and hyperlipidemia without prior cardiovascular events who were enrolled in the EMPATHY study. Data from 4746 patients were analyzed. The median RHR was 76 bpm. Patients were divided into four groups based on their baseline RHR ( < 60, 60-69, 70-79, and ≥80 bpm). Patients with a higher RHR were more likely to be younger and had a higher body mass index, blood pressure value, HbA1c value, and estimated glomerular filtration rate and a lower B-type natriuretic peptide value; they also had a higher proportion of current smoking status, neuropathy, and nephropathy. After adjusting for confounders, including the aforementioned risk factors, a RHR of 70-79 bpm and a RHR ≥ 80 bpm were significantly associated with cardiovascular events (hazard ratio 1.50, 95% CI 1.03-2.20; and hazard ratio 1.62, 95% CI 1.11-2.36; respectively) compared to a RHR of 60-69 bpm. The analysis using restricted cubic splines indicated that the cardiovascular risk seemed to be similarly high when the RHR range was ≥70 bpm. In conclusion, in T2DM patients with diabetic retinopathy and without known cardiovascular disease, a high RHR, particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to a RHR of 60-69 bpm. High resting heart rate (RHR), particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to RHR 60-69 bpm in patients with type 2 diabetes mellitus (T2DM), diabetic retinopathy, and hyperlipidemia, but without known cardiovascular disease.

Home-based cardiac rehabilitation using information and communication technology for heart failure patients with frailty.

AIMS: Cardiac rehabilitation (CR) is an evidence-based, secondary preventive strategy that improves mortality and morbidity rates in patients with heart failure (HF). However, the implementation and continuation of CR remains unsatisfactory, particularly for outpatients with physical frailty. This study investigated the efficacy and safety of a comprehensive home-based cardiac rehabilitation (HBCR) programme that combines patient education, exercise guidance, and nutritional guidance using information and communication technology (ICT). METHODS AND RESULTS: This study was a single-centre, open-label, randomized, controlled trial. Between April 2020 and November 2020, 30 outpatients with chronic HF (New York Heart Association II-III) and physical frailty were enrolled. The control group (n = 15) continued with standard care, while the HBCR group (n = 15) also received comprehensive, individualized CR, including ICT-based exercise and nutrition guidance using ICT via a Fitbit® device for 3 months. The CR team communicated with each patient in HBCR group once a week via the application messaging tool and planned the training frequency and intensity of training individually for the next week according to each patient's symptoms and recorded pulse data during exercise. Dietitians conducted a nutritional assessment and then provided individual nutritional advice using the picture-posting function of the application. The primary outcome was the change in the 6 min walking distance (6MWD). The participants' mean age was 63.7 ± 10.1 years, 53% were male, and 87% had non-ischaemic heart disease. The observed change in the 6MWD was significantly greater in the HBCR group (52.1 ± 43.9 m vs. -4.3 ± 38.8 m; P < 0.001) at a 73% of adherence rate. There was no significant change in adverse events in either group. CONCLUSIONS: Our comprehensive HBCR programme using ICT for HF patients with physical frailty improved exercise tolerance and improved lower extremity muscle strength in our sample, suggesting management with individualized ICT-based programmes as a safe and effective approach. Considering the increasing number of HF patients with frailty worldwide, our approach provides an efficient method to keep patients engaged in physical activity in their daily life.

Serial measurement of B-type natriuretic peptide and future cardiovascular events in patients with type 2 diabetes mellitus without known cardiovascular disease.

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients. METHODS: We analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study. RESULTS: Data from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5-29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low-low BNP group (baseline ≤35 pg/mL and 12-month ≤35 pg/mL), low-high BNP group as well as high-high BNP group was associated with cardiovascular events (HR: low-high, 2.05 [P = 0.004]; high-high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High-low BNP group tended to be associated with non-renal cardiovascular events (HR vs low-low: 2.05 [P = 0.056]). CONCLUSIONS: BNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

Delayed administration of epinephrine is associated with worse neurological outcomes in patients with out-of-hospital cardiac arrest and initial pulseless electrical activity: insight from the nationwide multicentre observational JAAM-OHCA (Japan Association for Acute Medicine) registry.

AIMS: The delayed administration of epinephrine has been proven to worsen the neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm or asystole. We aimed to investigate whether the delayed administration of epinephrine might also worsen the neurological outcomes of patients with witnessed OHCA and initial pulseless electrical activity (PEA). METHODS AND RESULTS: The JAAM-OHCA Registry is a multicentre registry including OHCA patients between 2014 and 2017. Patients with emergency medical services (EMS)-treated OHCA and initial PEA rhythm were included. The primary exposure was the time from the EMS call to the administration of epinephrine. The secondary exposure was the time to epinephrine dichotomized as early (≤15 min) or delayed (>15 min). The primary outcome was the achievement of a favourable neurological outcome, defined as Cerebral Performance Categories Scale 1-2 at 30 days after OHCA. Out of 34 754 patients with OHCA, 3050 patients were included in the present study. After adjusting for potential confounders, the delayed administration of the epinephrine was associated with a lower likelihood of achieving a favourable neurological outcome [adjusted odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93-0.99; P = 0.016]. The percentage of patients who achieved a favourable neurological outcome in the delayed epinephrine group was lower than that in the early epinephrine group (1.3% vs. 4.7%; adjusted OR 0.33; 95% CI 0.15-0.72; P = 0.005). A restricted cubic spline analysis demonstrated that delayed epinephrine administration could decrease the likelihood of achieving a favourable neurological outcome; this was significant within the first 10 min. CONCLUSIONS: The delayed administration of epinephrine was associated with worse neurological outcomes in patients with witnessed OHCA patients with initial PEA.

The use of angiotensin II receptor blocker is associated with greater recovery of cardiac function than angiotensin-converting enzyme inhibitor in dilated cardiomyopathy.

AIMS: Angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) have been shown to be associated with recovery of cardiac function in patients with dilated cardiomyopathy (DCM). The aim of this study was to assess comparative effectiveness of ACEis vs. ARBs on recovery of left ventricular ejection fraction (LVEF) among patients with DCM. METHODS AND RESULTS: We analysed the clinical personal records of DCM, a national database of the Japanese Ministry of Health, Labour and Welfare, from 2003 to 2014. Patients with LVEF < 40% and on either ACEis or ARBs were included. Eligible patients were divided into two groups according to the use of ACEis or ARBs. A one-to-one propensity case-matched analysis was used. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up. Out of 4618 eligible patients, 2238 patients received ACEis and 2380 patients received ARBs. Propensity score matching yielded 1341 pairs. Mean age was 56.0 years, 2041 (76.1%) were male, median duration of heart failure was 1 year, and mean LVEF was 27.6%. The primary outcome was observed more frequently in ARB group than in ACEi group (59.8% vs. 54.1%; odds ratio 1.26; 95% confidence interval 1.08-1.47; P = 0.003). The per-protocol analysis showed similar results (62.0% vs. 54.0%; odds ratio 1.39; 95% confidence interval 1.17-1.66; P < 0.001). The change in LVEF from baseline to 3 years of follow-up was greater in ARB group than in ACEi group (15.8 ± 0.4% vs. 14.0 ± 0.4%, P = 0.003). The subgroup analysis showed that this effect was observed independently of systolic blood pressure, heart rate, LVEF, chronic kidney disease, and concomitant use of beta-blockers and mineralocorticoid receptor antagonists. CONCLUSIONS: The use of ARBs was associated with LVEF recovery more frequently than ACEis among patients with DCM and reduced LVEF.