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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., Competing Interests: D.N. has received honoraria from Roche Diagnostics and grants from Bristol-Myers Squibb KK. Y. Sotomi has received honoraria from Daiichi-Sankyo, Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb. H.M. has received personal fees from Daiichi Sankyo, Kowa, Bayer and Pfizer Pharmaceuticals, and grant from Terumo. S.H. has received personal fees from Daiichi Sankyo, Bayer, Bristol-Myers Squibb KK, and Boehringer Ingelheim Japan, and grants from Roche Diagnostics, FUJIFILM Toyama Chemical, and Actelion Pharmaceuticals. Y. Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma, and Biotronik. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)

Background: Global longitudinal strain (GLS) can predict prognosis after myocardial infarction (MI). Tissue mitral annular displacement (TMAD) is another index of longitudinal left ventricular deformity, and is less dependent on image quality than GLS. We investigated the relationship between TMAD and GLS, and their ability to predict outcomes after MI. Methods and Results: GLS and TMAD were measured on echocardiograms 2 weeks after MI in 246 consecutive patients (median age 62 years, 85.7% male). TMAD was measured from apical 4- and 2-chamber views (TMAD 4ch and TMAD 2ch , respectively), and a mean value (TMAD av ) was calculated. TMAD 4ch , TMAD 2ch , and GLS were successfully measured in 240 (97.5%), 210 (85.3%) and 214 patients (87.0%), respectively. All TMAD parameters were significantly correlated with GLS (R=0.71-0.75) and left ventricular ejection fraction (LVEF; R=0.48-0.53). TMAD parameters were weakly correlated with peak creatine kinase (CK; R=0.20) and CK-MB (R=0.21-0.25). GLS and TMAD av were significantly associated with LVEF after 6 months (R=0.48-0.53) and all-cause mortality during the follow-up period (median 1,242 days). TMAD av discriminated patients with higher all-cause mortality when patients were divided into 3 groups, namely upper 25%, middle range, and lower 25% of TMAD av (P=0.041, log-rank test). GLS detected high-risk patients using 15.0% as a cut-off value. Conclusions: TMAD could be a simple and reliable alternative to GLS for predicting outcomes in patients with MI., Competing Interests: Katsuomi Iwakura has received remuneration from Boehringer Ingelheim, AstraZeneca, Ono Pharmaceutical, and Eli Lilly. Yasuhiko Sakata is a member of Circulation Reports’ Editorial Team. The remaining authors have no conflicts of interest to declare., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Background: Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown. Methods and Results: Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P<0.001), but there was no significant difference in embolic events (6.5% vs. 3.9%; P=0.606). Kaplan-Meier analysis also showed a significantly higher rate of bleeding events in the combination therapy group, but no significant difference in the rate of embolic events. Inverse probability of treatment weighting revealed that combination therapy was independently associated with an increased risk of bleeding (hazard ratio [HR] 2.98, 95% confidence interval [CI] 1.14-7.89, P=0.026), but not with the risk of embolic events (HR 0.30, 95% CI 0.04-2.59, P=0.275). Net clinical benefit analysis was almost negative for combination therapy vs. monotherapy. Conclusions: In patients with AF and LAT, combination therapy was significantly associated with an increased risk of bleeding events, but not with a reduced risk of embolic events., Competing Interests: S.H., K.I., A.H., M.M., Y.F., T.W., and H. Minamiguchi have received remuneration from Boehringer Ingelheim and Bayer. D.N. has received remuneration from Boehringer Ingelheim and Sanofi. Y.O. has received remuneration from Boehringer Ingelheim. K.K. has received remuneration from Boehringer Ingelheim, Bayer, and Sanofi. H. Mizuno has received remuneration from Boehringer-Ingelheim and Bayer, as well as research funding from Boehringer-Ingelheim. T. Kitamura has received remuneration from Bayer. Y.S. has received remuneration from Eizai, Boehringer-Ingelheim, Bayer, and Sanofi, served as a consultant to Boehringer-Ingelheim, Bayer, and Sanofi, holds patents with Eizai, Boehringer-Ingelheim, Bayer, and Sanofi, and has received research funding from Eizai, Bayer, and Sanofi. K.I. is a member of Circulation Reports ’ Editorial Team. The remaining authors have no conflicts of interest to report., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background: Little is known about factors associated with elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) at the convalescent stage and their effects on 1-year outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results: This study included 469 patients with HFpEF. Elevated NT-proBNP was defined as the highest quartile. The first 3 quartiles (Q1-Q3) were combined together for comparison with the fourth quartile (Q4). Median NT-proBNP concentrations in Q1-Q3 and Q4 were 669 and 3,504 pg/mL, respectively. Multivariate logistic regression analysis revealed that low albumin (odds ratio [OR] 2.44; 95% confidence interval [CI] 1.35-4.39; P=0.003), low estimated glomerular filtration rate (OR 5.83; 95% CI 3.46-9.83; P<0.001), high C-reactive protein (OR 2.09; 95% CI 1.21-3.63; P=0.009), and atrial fibrillation at discharge (OR 2.33; 95% CI 1.40-3.89; P=0.001) were associated with elevated NT-proBNP. Cumulative rates of all-cause mortality and heart failure rehospitalization were significantly higher in Q4 than in Q1-Q3 (P=0.001 and P<0.001, respectively). Incidence and hazard ratios of these adverse events increased when the number of associated factors for elevated NT-proBNP clustered together (P<0.001 and P=0.002, respectively). Conclusions: In addition to atrial fibrillation, extracardiac factors (malnutrition, renal impairment and inflammation) were associated with elevated NT-proBNP at the convalescent stage, and led to poor prognosis in patients with HFpEF., Competing Interests: D.N. has received honoraria from Roche Diagnostics K.K.; S.H. and Y.S. have received grant support from Roche Diagnostics K.K. and Fuji Film Toyama Chemical. The other authors have no conflicts of interest to declare., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background: Studies comparing the cardiac consequences of hydrophilic and lipophilic statins in experimental and clinical practice settings have produced inconsistent results. In particular, evidence focusing on diabetic patients after acute myocardial infarction (AMI) is lacking. Methods and Results: From the Osaka Acute Coronary Insufficiency Study (OACIS) registry database, 1,752 diabetic patients with AMI who were discharged with a prescription for statins were studied. Long-term outcomes were compared between hydrophilic and lipophilic statins, including all-cause death, recurrent myocardial infarction (re-MI) and admission for heart failure (HF) and a composite of these (major adverse cardiac events; MACE). During a median follow-up period of 1,059 days, all-cause death, non-fatal re-MI, admission for HF, and MACE occurred in 95, 89, 112 and 249 patients, respectively. Although there was no significant difference between statins in the risk of all-cause death, re-MI and MACE, the risk of HF admission was significantly lower in patients with hydrophilic than lipophilic statins before (adjusted hazard ratio [aHR], 0.560; 95% CI: 0.345-0.911, P=0.019) and after (aHR, 0.584; 95% CI: 0.389-0.876, P=0.009) propensity score matching. Hydrophilic statin use was consistently associated with lower risk for HF admission than lipophilic statins across the subgroup categories. Conclusions: In the present diabetic patients with AMI, hydrophilic statins were associated with a lower risk of admission for HF than lipophilic statins., Competing Interests: Yasuhiko S. has received honoraria from Kowa. S.H. has received honoraria from Kowa and Daiichi-Sankyo. H.M. has received honoraria from Daiichi-Sankyo. T. Kitamura has received honoraria from AstraZeneca and Bristol-Myers Squibb. A.S. has received honoraria from Daiichi-Sankyo. M.H. has received honoraria from Boehringer-Ingelheim, Bayer, and Tanabe-Mitsubishi Pharma. I.K. has received honoraria from Pfizer, Daiichi-Sankyo, and MSD, and research grants from Kowa, Astellas, Daiichi-Sankyo and Mitsubishi Tanabe Pharma. Yasushi S. has received honoraria from Pfizer, Daiichi-Sankyo, Bristol-Myers Squibb, Kowa, Mitsubishi Tanabe Pharma, Astellas, MSD, Shionogi, AstraZeneca, and Novartis. Yasuhiko S., I.K. are members of Circulation Reports’ Editorial Team. The other authors declare no conflicts of interest., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background: Left ventricular reverse remodeling (LVRR) is a favorable response in non-ischemic, non-valvular cardiomyopathy (NICM) patients. Recently, 18-lead body surface electrocardiography (ECG), the standard 12-lead ECG with synthesized right-sided/posterior chest leads, has been developed, but its predictive value for LVRR has not been evaluated. Methods and Results: Of 216 consecutive hospitalized NICM patients with LV ejection fraction (LVEF) ≤35%, we studied 125 who received optimization of their heart failure treatment and had 18-lead ECG and echocardiography data available for evaluating LVRR, defined as an absolute increase in LVEF ≥10% concomitant with LVEF ≥35% after 1-year optimized treatment. Most 18-lead ECG parameters in the NICM patients differed from those in 312 age- and body mass index-matched subjects with normal echocardiography. LVRR occurred in 59 NICM patients and they had a larger QRS amplitude in the limb leads (I, II, aVR, and aVF), precordial leads (V3-V6), and synthesized leads (syn-V4R-5R), decreased QRS axis and duration, and lower prevalence of fragmented QRS than those without LVRR. The ECG score using 3 selected parameters (QRS amplitude in aVR ≥675 µV; QRS duration <106 ms without fragmentation; and QRS axis <67°) was associated with the incidence of LVRR even after adjusting for optimized treatment. Conclusions: The standard 12-lead ECG parameters are sufficiently predictive of LVRR in NICM patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)

Background: Accurate prognosis for heart failure (HF) survival is important for quality of life, treatment decisions, and early evaluation of new therapies and devices. Here, we developed a multivariate risk model for predicting survival in Japanese patients with HF, using parameters that are readily observable in a clinical setting. Methods and Results: We analyzed data for 1,214 adults with HF (EF <35%). Of 424 available clinical baseline factors in the derivation dataset, 17 candidate predictors were identified on Cox proportional hazards regression. These predictors were assessed for clinical relevance and tested in candidate models using cross-validated 5-year C-statistics. This process yielded a set of 14 covariates with good accuracy for predicting actual 5-year survival: age; LVEF; albumin; BMI; Hb; sodium; history of renal dysfunction, diabetes, or chronic dialysis; times HF recurred or required readmission to the hospital; use of cardiac drip, thiazide diuretic, or per oral inotropic agent; and loop diuretic dosage. These 14 variables were used to establish the Japan Heart Failure Model (JHFM) for predicting survival in patients with HF. When applied to an independent validation dataset, the results from the JHFM were closer to actual survival than those of the Seattle Heart Failure Model. Conclusions: JHFM predictions for 5-year survival had good accuracy for Japanese patients with HF. The JHFM uses parameters that can be measured at any hospital., (Copyright © 2019, THE JAPANESE CIRCULATION SOCIETY.)