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Background: The effects of myocarditis after mRNA COVID-19 vaccination (mCV) on myocardial tissue, and the association between cardiomyocyte injury and clinical presentation, are not fully understood., Methods and Results: We retrospectively registered patients clinically diagnosed with myocarditis after the first or second mCV who underwent endomyocardial biopsy or autopsy from 42 participating centers in Japan. We investigated the histological features and their association with clinical presentation based on cardiomyocyte injury. Forty patients who underwent endomyocardial biopsy were included in the study. Of these, 19 (47.5%) showed mild lymphocytic infiltration and interstitial edema without cardiomyocyte injury. The remaining 21 (52.5%) patients showed cardiomyocyte injury accompanied by infiltrating inflammatory cells: 11 with lymphocytic infiltration, 7 with eosinophilic infiltration, and 3 with myocarditis with both lymphocyte and eosinophil infiltration. Compared with patients without cardiomyocyte injury, those with cardiomyocyte injury were clinically characterized by older age, a balanced sex distribution, less frequent chest pain, and a lower left ventricular ejection fraction. Fifteen of 21 (71.4%) patients with cardiomyocyte injury developed fulminant myocarditis, with 13 (86.7%) requiring mechanical circulatory support; in contrast, none of those without cardiomyocyte injury developed fulminant myocarditis (P<0.001)., Conclusions: Our histological examination of patients with myocarditis after mCV revealed varying degrees of cardiomyocyte injury, ranging from pronounced to absent, along with various types of myocarditis. Cardiomyocyte injury was strongly associated with the severity of myocarditis.

Background: It is still unclear whether changes in right ventricular function are associated with prognosis in heart failure (HF) patients. This study aimed to examine the prognostic effect of changes in right ventricular fractional area change (RVFAC)., Methods and results: This study enrolled 480 hospitalized patients with decompensated HF, and measured RVFAC with echocardiography at discharge (first examination) and post-discharge in the outpatient setting (second examination). RVFAC was divided into 3 categories: >35% in 314 patients, 25-35% in 108 patients, and <25% in 58 patients. Next, based on changes in RVFAC from the first to the second examination, the patients were further classed into 4 groups: (1) Preserved/Unchanged (preserved and unchanged RVFAC, n=235); (2) Reduced/Improved (improved RVFAC in at least 1 category, n=106); (3) Reduced/Unchanged (reduced and unchanged RVFAC, n=47); and (4) Preserved or Reduced/Worsened (deteriorated RVAFC in at least 1 category, n=92). Multivariate logistic regression analysis revealed that chronic kidney disease and anemia were the predictors of the preserved or reduced/worsened RVFAC. In the Kaplan-Meier analysis, changes in RVFAC were associated with the cardiac event rate and all-cause mortality. In the multivariable Cox proportional hazard analysis, the preserved or reduced/worsened RVFAC was an independent predictor of cardiac events and all-cause mortality., Conclusions: Changes in RVFAC were associated with post-discharge prognosis in hospitalized heart failure patients.

Background: It has recently been reported that the simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition, which excludes 6 rare criteria, is comparable to the original ARC-HBR definition in predicting major bleeding in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention. In this study, we investigated whether the simplified ARC-HBR definition could be applied to patients with heart failure (HF) to identify those at high bleeding risk (HBR)., Methods and results: In all, 2,437 patients hospitalized for HF were enrolled in this study. Patients were divided into 2 groups based on the simplified ARC-HBR definition: those at HBR (n=2,026; 83.1%) and those not (non-HBR group; n=411; 16.9%). The HBR group was older (72.0 vs. 61.0 years; P<0.001) and had a lower prevalence of CAD (31.1% vs. 36.5%; P=0.034) than the non-HBR group. Kaplan-Meier analysis showed that post-discharge bleeding events defined as hemorrhagic stroke or gastrointestinal bleeding were more frequent in the HBR than non-HBR group (log-rank P<0.001). The simplified ARC-HBR definition accurately predicted bleeding events (Fine-Gray model; hazard ratio 2.777, 95% confidence interval 1.464-5.270, P=0.001)., Conclusions: The simplified ARC-HBR definition predicts a high risk of bleeding events in patients with HF.

Background: Heart failure (HF) and cancer (CA) are becoming increasingly prevalent as the population ages. We aimed to evaluate prior history and occurrence of CA and its prognostic impact on HF., Methods and results: Consecutive hospitalized HF patients (n=2,103) were divided into 2 groups according to prior history of CA: non-prior-CA group (n=1,828) and prior-CA group (n=275). Compared with the non-prior-CA group, the prior-CA group were older, and had higher prevalence of chronic kidney disease, anemia, and atrial fibrillation (P<0.05). In contrast, sex, other comorbidities, levels of natriuretic peptide and ejection fraction were comparable between groups. We focused on newly diagnosed CA after discharge for HF. In the follow-up period (median 623 days), 114 (6.2%) patients in the non-prior-CA and 17 (6.2%) patients in the prior-CA groups were newly diagnosed as having CA. Additionally, 83 (3.9%) CA-related patient deaths occurred (median 776 days). In the Kaplan-Meier analysis (median 1,037 days), not only all-cause death but also cardiac event rate was significantly higher in the prior-CA group than in the non-prior-CA group (log-rank P<0.01). In the Cox proportional hazard analysis, CA history was a predictor of cardiac event rate (HR 1.450, 95% CI 1.134-1.822), as well as all-cause death (HR 2.483, 95% CI 2.034-3.030)., Conclusions: Prior-CA history was associated with high cardiac event and mortality rates. CA is notable comorbidity in HF patients.

Background: Insomnia is associated with incident heart failure (HF), but the clinical significance and impact of insomnia on HF remain unclear., Methods and results: Consecutive 1,011 patients admitted for HF were divided into 2 groups according to the presence of insomnia: HF with insomnia (insomnia group, n=519) and HF without insomnia (non-insomnia group, n=492). We compared (1) cardiac event rates including cardiac death and worsening HF; and (2) underlying clinical background including laboratory data, echocardiographic data, and cardiopulmonary exercise test between the 2 groups. On Kaplan-Meier analysis, cardiac event rate was significantly higher in the insomnia group than in the non-insomnia group (39.1 vs. 23.4%, P<0.001). The insomnia group, as compared with the non-insomnia group, had (1) higher plasma renin activity (P=0.042), renin concentration (P=0.007), and aldosterone (P=0.047); (2) lower peak V̇O2(14.9 vs. 16.3 ml/kg/min, P=0.002) and higher V̇E/V̇CO2slope (36.0 vs. 33.5, P=0.001); and (3) similar B-type natriuretic peptide and left ventricular ejection fraction. Importantly, on multivariate Cox proportional hazard analysis after adjusting for potential confounding factors, insomnia was an independent predictor of cardiac events in HF patients (hazard ratio, 1.899; P<0.001)., Conclusions: Insomnia is an independent predictor of cardiac events in HF patients. HF patients with insomnia have activated renin-angiotensin-aldosterone system and lower exercise capacity. (Circ J 2016; 80: 1571-1577).

Background: The impact of peripheral artery disease (PAD) on heart failure (HF) prognosis remains unclear., Methods and Results: A total of 388 consecutive decompensated HF patients were divided into 2 groups based on the presence of PAD: HF with PAD (PAD group, n=101, 26.0%) and HF without PAD (non-PAD group, n=287, 74.0%). We compared clinical features, echocardiographic parameters, cardiopulmonary exercise testing results, laboratory findings, as well as cardiac, non-cardiac, and all-cause mortality between the 2 groups. The PAD group, as compared with the non-PAD group, had (1) higher prevalence of coronary artery disease (40.6 vs. 27.5%, P=0.011) and cerebrovascular disease (34.7 vs. 18.2%, P=0.001); (2) higher tumor necrosis factor-α (1.82 vs. 1.49 pg/ml, P=0.023), C-reactive protein (0.32 vs. 0.19 mg/dl, P=0.045), and troponin T (0.039 vs. 0.021 ng/ml, P=0.019); (3) lower LVEF (42.4 vs. 48.5%, P<0.001); (4) lower peak V̇O2(13.4 vs. 15.9 ml·kg(-1)·min(-1), P=0.001); and (5) higher V̇E/V̇CO2slope (38.8 vs. 33.7, P<0.001). On Kaplan-Meier analysis, cardiac, non-cardiac, and all-cause mortality were significantly higher in the PAD group than in the non-PAD group (P<0.05, respectively). On Cox proportional hazard analysis after adjusting for confounding factors, PAD was an independent predictor of cardiac and all-cause mortality (P<0.05, respectively) in HF patients., Conclusions: PAD was common and an independent predictor of cardiac and all-cause mortality in HF patients.

Background:  Cardiac troponins are independent predictors of cardiac mortality in patients with heart failure (HF). Recently, elevation of troponins was described in non-cardiac diseases such as stroke and infection, among others, but it remains unclear whether high-sensitivity troponin T (hs-TnT) predicts non-cardiac mortality in HF patients., Methods and Results:  Four-hundred and forty-four consecutive HF patients admitted to hospital for the treatment of decompensated HF were divided into 2 groups based on median hs-TnT: group L (<0.028ng/ml, n=220) and group H (≥0.028ng/ml, n=224). We compared all-cause mortality and echocardiographic findings between the 2 groups. In the follow-up period (mean 472 days), 77 deaths (49 cardiac deaths and 28 non-cardiac deaths) were observed. The event-free rate was significantly lower in group H than in group L for non-cardiac death (P=0.025), cardiac death (P<0.001), and all-cause mortality (P<0.001). On multivariate Cox proportional hazard analysis, high hs-TnT was found to be an independent predictor of non-cardiac death (P=0.042), cardiac death (P<0.001) and all-cause mortality (P<0.001) in HF patients after adjusting for risk factors. Regarding echocardiographic parameters, left ventricular wall thickness was higher (P<0.001), and ejection fraction was lower (P=0.011) in group H than in group L., Conclusions:  Hs-TnT is an independent predictor not only of cardiac mortality, but also of non-cardiac mortality in HF patients.

Background: Although myocardial fibrosis plays an important role in the progression of heart failure (HF), its prognostic impact still remains to be clarified., Methods and Results: A total of 172 consecutive patients with chronic HF, who underwent cardiac catheterization and endomyocardial biopsy between January 2001 and September 2008, were examined. They were divided into 2 groups: HF with preserved ejection fraction (HFPEF; left ventricular ejection fraction [LVEF] ≥ 50%, n=81); and HF with reduced LVEF (HFREF; LVEF < 50%, n=91). The collagen volume fraction (CVF) in biopsy samples was calculated and its prognostic impact examined. Mean follow-up in the HFPEF and the HFREF groups was 41 ± 33 months and 41 ± 26 months, respectively. Although CVF was similar between the 2 groups (1.83 ± 1.54% vs. 2.07 ± 2.35%), CVF was significantly correlated with LV end-diastolic pressure in the HFREF group but not in the HFPEF group. When HF stage was adjusted, the long-term prognosis was comparable between the 2 groups. When the patients were divided into 2 groups according to median CVF, however, severe fibrosis was a significant predictor for all-cause death (P=0.014) and cardiac events (P=0.02) in the HFREF, but not in the HFPEF group., Conclusions: Myocardial fibrosis evaluated on biopsy samples is a useful indicator for long-term survival, suggesting that it may be an important therapeutic target as well.

Background: Pulmonary hypertension (PH) still remains a serious disease, for which the plasma level of brain natriuretic peptide (BNP) and hemodynamic variables (eg, cardiac index: CI) are established prognostic factors. The aim of the present study was to identify new additional prognostic factors of the disorder to improve the management of PH., Methods and Results: The study cohort comprised 136 consecutive PH patients admitted to hospital from 1974 to 2008, all of whom were closely followed every 6-12 months. During the follow-up period of 53.5+/-4.5 [SEM] months, 47 patients died of cardiopulmonary causes. The patients who were initially treated with monotherapy showed improved pulmonary hemodynamics when subsequently treated with combination therapy. Multivariate analysis showed that BNP and CI were significant and independent prognostic factors in all PH patients. However, in PH patients with low CI at diagnosis, only CI improvement by PH therapy was a significant and independent prognostic factor. Indeed, the patients with low CI at diagnosis (CI <2.5) followed by subsequent normalization in response to therapy (CI > or =2.5) showed a significantly better survival compared with those without such normalization., Conclusions: CI normalization in response to treatment is an independent new prognostic factor of PH in patients with low CI at diagnosis, suggesting the importance of intensive therapy to achieve CI normalization.

Despite recent advances in the understanding and etiology of cardiovascular disease, it remains the leading cause of morbidity and mortality worldwide. A great deal of research has been dedicated to investigating and identifying plaque instability: the so-called "vulnerable plaque". A reliable, in vivo, imaging method capable of identifying plaque characteristics associated with high-risk plaque will be immensely useful for evaluating plaque status and predicting future events. With excellent soft-tissue contrast and resolution, magnetic resonance imaging (MRI) has the ability to visualize features of vulnerable plaques, as well as perform longitudinal studies on the etiology, progression, and regression of atherosclerotic plaque. This review will cover the current state-of-the-art and new developments in carotid MRI to characterize atherosclerosis and its use in clinical diagnoses and longitudinal studies to understand mechanisms of lesion progression and regression.

Background: The aim of this study was to assess whether and how infarct size (IS) reduction by postconditioning is modified in the heart with coronary stenosis (CS), and how beta-blocker treatment affects it., Methods and Results: The IS was assessed by 30-min acute coronary occlusion and 24-h reperfusion in rat hearts in which CS had been induced. Modification of IS by postconditioning and the effects of daily carvedilol treatment were measured, together with reperfusion injury - salvage kinase activities. Four weeks after CS induction, any reduction of IS by postconditioning was lost, whereas it reduced IS in rats without CS. In the hearts without CS, postconditioning activated both the ERK and Akt pathway. However, in the hearts with CS, postconditioning failed to do so. In hearts with CS plus daily carvedilol treatment, postconditioning reduced IS compared with the hearts without carvedilol, although postconditioning did not activate the Akt and ERK pathways., Conclusion: CS impaired Akt and ERK activation, resulting in a failure to reduce IS by postconditioning. Carvedilol treatment restored the IS reduction by postconditioning, possibly via other mechanism(s) of the ERK and Akt pathways.

Background: The goal of the present study was to examine the cardiac configuration and pulmonary vascular changes in patients with portopulmonary hypertension (PPHTN) and compare them with those of idiopathic pulmonary arterial hypertension (IPAH)., Methods and Results: The subjects were 10 patients with PPHTN and 18 with IPAH. In PPHTN, the increases in the right ventricular end-diastolic volume index (89+/-19 vs 128+/-50 ml/m2; p=0.04), right end-systolic volume index (50+/-19 vs 95+/-47 ml/m 2; p=0.02) and right ventricular mass index (47+/-18 g/m2 vs 79+/-31; p=0.04) were low compared with IPAH. The decrease in the right ventricular ejection fraction was also low in PPHTN (45+/-10 vs 28+/-13%; p=0.01). The degree of sparse arborization and abrupt narrowing on wedged pulmonary angiography was moderate in PPHTN compared with IPAH. In PPHTN, the proximal pulmonary arteries were dilated near the segmental arteries, which were narrow in IPAH., Conclusion: Changes in the configuration of the heart were moderate in PPHTN compared with those in IPAH. The degree of sparse arborization and abrupt narrowing were also moderate in PPHTN.