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BackgroundIt is widely recognized that metabolic disorder is associated with pulmonary hypertension (PH). It is known that hypoxia-induced elevated pulmonary artery pressure in mice returns to normal pressure during reoxygenation. However, it is still unclear how metabolic disorder affects the reverse remodeling of pulmonary arteries. In this study, we investigated the effects of high-fat diet (HFD) on the decrease in pulmonary artery pressure and reverse remodeling of pulmonary arteries in mice with hypoxia-induced PH.MethodsWe used female C57BL/6 mice aged 8 weeks. After being exposed to hypoxia (10% oxygen for four weeks) to induce PH, the mice were returned to normoxic conditions and randomized into a normal diet (ND) group and HFD group. Both groups were fed with their respective diets for 12 weeks.ResultsThe Fulton index and right ventricular systolic pressure measured by a micro-manometer catheter were significantly higher in the HFD group than in the ND group at 12 weeks after reoxygenation. The medial smooth muscle area was larger in the HFD group. Caspase-3 activity in the lung tissue of the HFD group was decreased, and the apoptosis of pulmonary smooth muscle cells was suppressed after reoxygenation. Moreover, the expression levels of peroxisome proliferator-activated receptor-γ and apelin were lower in the HFD group than in the ND group.ConclusionsThe results suggest that metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced PH during reoxygenation.

It has been reported that the pattern of hepatic vein (HV) waveforms determined by abdominal ultrasonography is useful for the diagnosis of hepatic fibrosis in patients with chronic liver disease. We aim to clarify the clinical implications of HV waveform patterns in patients with heart failure (HF).We measured HV waveforms in 350 HF patients, who were then classified into 3 categories based on their waveforms: those with a continuous pattern (C group); those whose V wave ran under the baseline (U group), and those with a reversed V wave (R group). We performed right-heart catheterization, and examined the rate of postdischarge cardiac events, such as cardiac death and rehospitalization due to worsening HF.The number of patients in each of the 3 HV waveform groups was as follows: C group, n = 158; U group, n = 152, and R group, n = 40. The levels of B-type natriuretic peptide (R vs C and U; 245.8 vs 111.7 and 216.6 pg/mL;Among HF patients, those with reversed V waves had higher right atrial pressure and were at higher risk of adverse prognosis.Nous avons appris que le tracé ondulatoire de la veine hépatique (VH) à l’échographie abdominale est utile au diagnostic de la fibrose hépatique chez les patients atteints d’une maladie chronique du foie. Nous avons pour objectif de clarifier les implications cliniques des tracés ondulatoires de la VH chez les patients atteints d’insuffisance cardiaque (IC).Nous avons mesuré les ondulations de la VH de 350 patients atteints d’IC et les avons ensuite classifiés en trois catégories selon leurs ondulations : ceux qui avaient un tracé continu (groupe C); ceux dont l’onde V se présentait selon les valeurs de référence (groupe U); ceux qui avaient une onde V inversée (groupe R). Nous avons réalisé un cathétérisme cardiaque droit et examiné le taux d’événements cardiaques après la sortie de l’hôpital tels que la mort d’origine cardiaque et la réhospitalisation en raison de l’aggravation de l’IC.Le nombre de patients dans chacun des trois groupes d’ondulations de la VH était réparti comme suit : groupe C, n = 158; groupe U, n = 152 et groupe R, n = 40. Les concentrations en peptides natriurétiques de type B (RChez les patients atteints d’IC, ceux qui avaient des ondes V inversées avaient une pression plus élevée de l’oreillette droite et étaient exposés à un risque plus élevé de pronostic défavorable.

Objectives This study sought to investigate the incidence and characteristics of the real-world safety profile of second-generation cryoballoon ablation (2nd-CBA) in Japan. Background Pulmonary vein isolation using second-generation cryoballoons is an accepted atrial fibrillation ablation strategy. Methods This multicenter observational study included 4,173 patients with atrial fibrillation (3,807 paroxysmal) who underwent a 2nd-CBA in 18 participating centers. The baseline data and details of all procedure-related complications within 3 months post-procedure in consecutive patients from the first case at each center were retrospectively collected. Results Adjunctive ablation after the pulmonary vein isolation was performed in 2,745 (65.8%) patients. Complications associated with the entire procedure were observed in 206 (4.9%) total patients, and in the multivariate analysis, the age (odds ratio: 1.015; 95% confidence interval: 1.001 to 1.030; p = 0.035) and study period were predictors. Air embolisms manifesting as ST-segment elevation and cardiac tamponade requiring drainage occurred in 63 (1.5%) and 15 (0.36%) patients, respectively. Six (0.14%) patients had strokes/transient ischemic attacks, among whom 5 underwent ablation under an interrupted anticoagulation regimen. No atrioesophageal fistulae occurred; however, 10 (0.24%) patients had symptomatic gastric hypomotility. Esophageal temperature monitoring did not reduce the incidence, and the incidence was significantly higher in patients with adjunctive posterior wall isolations or mitral isthmus ablation than those without (p = 0.004). Phrenic nerve injury occurred during the 2nd-CBA in 58 (1.4%) patients; however, all were asymptomatic and recovered within 13 months. One patient died of aspiration pneumonia. Conclusions This study had a high safety profile of 2nd-CBA despite including the early experience and high rate of adjunctive ablation. Care should be taken for air embolisms during 2nd-CBA.

Background: The impact of preprocedural visit-to-visit blood pressure variability (BPV) on pulmonary vein isolation (PVI) outcome in patients with hypertension (HTN) and atrial fibrillation (AF) remains unclear. Methods and Results: This study enrolled 138 AF patients with HTN who underwent successful PVI. Patients were classified into 2 groups, those with AF recurrence (AF-Rec; n=42) and those without AF recurrence (No-AF-Rec; n=96). Blood pressure (BP) was measured at least 3 times during sinus rhythm, and systolic and diastolic BPV (Sys-BPV and Dia-BPV, respectively) were defined as the standard deviation of BP. Clinical characteristics were compared between the 2 groups, and the relationship between BPV and AF recurrence was investigated. Sys-BPV and Dia-BPV were significantly higher in the AF-Rec than No-AF-Rec group (Sys-BPV: 10.6±3.7 vs. 6.9±3.5; Dia-BPV: 7.3±3.1 vs. 4.8±3.0; P9.1 and Dia-BPV >5.7 (P9.1 and Dia-BPV >5.7 were independent predictors of AF recurrence (hazard ratios 3.736 and 2.958, respectively; P

Objective It has been reported that anti-mitochondrial antibodies (AMAs) recognize mitochondrial antigens and are associated with some diseases involving multiple organs, such as primary biliary cholangitis, Sjögren syndrome, Hashimoto's thyroiditis, systemic sclerosis, interstitial pneumoniae, dilated cardiomyopathy, and tubulointerstitial nephritis. In the current study, we examined the prevalence of AMAs in patients with dilated cardiomyopathy (DCM) and their clinical characteristics. Methods We enrolled 270 patients with DCM. We measured serum AMAs and analyzed the associated factors. Out of the 270 patients, positive AMAs were detected in 3 patients (1.1%; mean age, 68 years old; 2 men). These three patients had a significantly higher prevalence of primary biliary cholangitis and myopathy and levels of alanine alkaline phosphatase than those who were negative for said antibodies. There were no significant differences in the levels of B-type natriuretic peptide, aspartate transaminase, and left ventricular ejection fraction between these groups of patients. During the follow-up period, two of the three patients died due to respiratory failure. The other patient survived but experienced type II respiratory failure. Conclusion The prevalence of AMAs in 270 DCM patients was only 1.1%, and these patients suffered from respiratory failure.

Pulmonary vein isolation is an established method for the catheter ablation of atrial fibrillation. Esophageal thermal injuries, such as esophageal erosion, ulceration and periesophageal nerve injury leading to gastric hypomotility, are important complications associated with pulmonary vein isolation. In this review article, we describe the mechanisms, characteristics and the predictors of esophageal thermal injury associated with pulmonary vein isolation.

Background Both increases in red cell distribution width (RDW) levels and autonomic dysfunction are considered to be correlated with worsening heart failure. However, the relation of RDW levels to autonomic function remains uncertain. We aimed to investigate the association of RDW levels in heart failure with autonomic function, evaluated by heart rate variability (HRV) and heart rate turbulence (HRT), and prognosis. Methods We studied 222 hospitalized patients with stable heart failure before discharge, and Holter recordings (HRV and HRT) were performed. Additionally, RDW levels were measured, and high RDW was defined as over 14.5%. We then divided the patients into two groups based on RDW levels: high RDW group (>14.5%, n = 92) and low RDW group (≤14.5%, n = 130). The relation of RDW to autonomic function and prognosis was assessed. Results In the high RDW group, severely impaired HRV and HRT were found compared to the low RDW group. In the linear regression analysis after the adjustment of multiple confounders, RDW levels were correlated with a low‐frequency (LF) to high‐frequency (HF) ratio and very low‐frequency (VLF) power (LF to HF ratio, β = −0.146, P = .027, and VLF power, β = −0.137, P = .041, respectively). During the observation period (median 1400 days), cardiac events (re‐hospitalization of heart failure, cardiac death or sudden death) were found in 73 (32.8%) patients. The Kaplan‐Meier analysis demonstrated that the high RDW group had a higher rate of cardiac events compared to the low RDW group (45.6% vs 23.8%, log‐rank P, In the current study, we aimed to validate the association between red cell distribution width (RDW) and cardiac autonomic function assessed using heart rate variability and heart rate turbulence in patients with heart failure. As a result, we demonstrated that high RDW levels were associated with cardiac autonomic dysfunction, resulting in poor clinical outcomes.

Background To investigate the clinical implication of the temporal difference in atrial fibrillation (AF)‐onset in acute decompensated heart failure (ADHF) and its impact on post‐discharge prognosis. Methods 336 new‐onset ADHF patients without any history of AF before admission were enrolled (201 males, 63 ± 16 year‐old) and classified into two groups based on their history of AF: the Control group (No AF was detected during hospitalization, n = 278), and the In‐hos‐AF group (AF occurred during hospitalization, n = 58). Post discharge prognosis including rehospitalization due to worsening HF, cardiac death, all‐cause death and cerebrovascular event were compared. Results Kaplan‐Meier analysis demonstrated that the incidence of rehospitalization due to HF, cardiac death, all‐cause death and cerebrovascular event in the In‐hos‐AF group was not significantly different from that in the Control group (P > 0.05 respectively). However, when AF recurred in the In‐hos‐AF group patients (n = 24, 41%) after discharge, the incidence of rehospitalization due to HF and cardiac deaths were higher than those without AF recurrence (P = 0.018 and P = 0.027 respectively). Cox proportional analysis revealed that AF developing after discharge was proven to be an independent risk factor for rehospitalization due to HF (HR 1.845, P = 0.043), cardiac death (HR 3.562, P = 0.013) and all‐cause deaths (HR 2.138, P = 0.020). Conclusion Clinical outcomes of new‐onset in‐hospital AF patients were as good as those without AF history until AF recurrence. However, AF recurrence led to worse prognosis. Therefore, treatment for new‐onset in‐hospital AF in ADHF patients might be postponed until AF recurrence., Clinical outcome in the new‐onset in‐hospital AF in patients with ADHFD, compared with those who had no history of AF.

Background Sleep-disordered breathing (SDB) and blood pressure variability (BPV) are strongly associated with cardiovascular diseases. Recently, pulse transit time (PTT) has enabled the monitoring of beat-to-beat BP; however, little is known about its clinical utility. The present study aimed to clarify the impact of SDB on very short-term BPV determined by PTT-based BP monitoring (PTT-BP). Methods We analyzed 242 patients with suspected SDB. PTT-BP was continuously recorded overnight together with a portable sleep monitor. PTT index was defined as the average number of transient rises in PTT-BP (≥12 mmHg) within 30 s/h. We compared PTT-BP values with each SDB parameter, and examined the association between BPV and subclinical organ damage. Results Standard deviation (SD) of systolic, mean or diastolic PTT-BP, which indicates very short-term BPV, was significantly correlated with apnea--hypopnea index (AHI) and oxygen desaturation index (ODI). PTT index was positively associated with AHI, ODI, and minimal SpO2. Regression analyses showed that AHI and ODI were significant variables to determine systolic, mean, or diastolic PTT-BP SD and PTT index. Logistic regression analyses demonstrated that diastolic PTT-BP SD significantly influenced the presence of chronic kidney disease and left ventricular hypertrophy. Conclusion SDB severity was closely associated with very short-term BP variability, and diastolic PTT-BP SD might be an important factor linked to subclinical organ damage. PTT-BP measurement may be useful to evaluate very short-term BPV during the night.

OBJECTIVES Hybrid PET/MRI is useful for the simultaneous evaluation of both -ammonia PET and MRI data. The aim of the current study was to compare the accuracy of gated -ammonia PET with MRI for the measurement of left ventricular volumes and function in patients with coronary artery disease (CAD), using simultaneous acquisitions on a hybrid PET/MRI system. METHODS Fifty-one consecutive patients with suspected CAD who underwent -ammonia PET/MRI were enrolled in this study. End-diastolic volume (EDV), end-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were simultaneously evaluated using both gated -ammonia PET and cine MRI. Regional wall motion was visually scored on a 4-point scale using a 17-segment model for both methods. RESULTS The correlations between each EDV (R = 0.99, P < 0.001), ESV (R = 0.98, P < 0.001), and LVEF (R = 0.99, P = 0.001) measured by gated -ammmonia and MRI were very high. These high correlations were also observed in postmyocardial infarction patients. Furthermore, the regional wall motion scores determined on gated -ammonia PET and MRI showed an agreement of 89.0% with a kappa value of 0.82 ± 0.02. CONCLUSION EDV, ESV, LVEF, and regional wall motion measured by gated -ammonia PET were highly correlated with those measured by MRI.

Background The clinical significance of premature ventricular complexes (PVCs) in heart failure (HF) remains unclear. We aimed to clarify the associations of PVC burden with re‐hospitalization and cardiac death in HF patients. Methods We studied 435 HF patients (271 men, mean age 65 years). All patients were hospitalized for worsening HF. After optimal medications, echocardiography, 24 hours Holter monitoring and cardiopulmonary exercise testing were performed before discharge. The clinical characteristics and outcomes of the HF patients were investigated. Results During a median follow‐up period of 2.3 years, there were 125 (28.7%) cardiac events (re‐hospitalization due to worsening HF, fatal arrhythmias, or cardiac death). The patients with cardiac events had higher PVC burden compared to those without (median 0.374%/d [interquartile range 0.013‐1.510] vs median 0.026%/d [interquartile range 0.000‐0.534], P 0.145%/d) to be a predictive factor of cardiac events (area under the curve: 0.64). Kaplan‐Meier analysis demonstrated that cardiac events were more frequent in patients with high‐PVC burden (>0.145%/d, n = 194) compared to those with low‐PVC burden (≤0.145%/d, n = 241). Furthermore, the high‐PVC burden patients had left ventricular (LV) and atrial dilatation, reduced LV ejection fraction, and impaired exercise capacity, compared to the low‐PVC burden patients. In Cox proportional hazards analysis, high‐PVC burden was significantly associated with cardiac events with a hazard ratio of 2.028 (95% confidence interval: 1.418‐2.901, P, The frequency of premature ventricular complex after optimal medication was significantly associated appropriate implantable cardioverter defibrillator therapy, readmission due to worsening heart failure or cardiac death in hospitalized patients with heart failure, even if the frequency was low (>0.145%/d).

BackgroundD-dimer is a sensitive biomarker for cancer-associated thrombosis, but little is known about its significance on cancer therapeutics-related cardiac dysfunction (CTRCD).MethodsConsecutive 169 patients planned for cardiotoxic chemotherapy were enrolled and followed up for 12 months. All patients underwent echocardiography and blood test at baseline and at 3-, 6-, and 12 months.ResultsThe patients were divided into two groups based on the level of D-dimer (>1.65 μg/ml or ≦ 1.65 μg/ml) at baseline before chemotherapy: high D-dimer group (n = 37) and low D-dimer group (n = 132). Left ventricular ejection fraction (LVEF) decreased at 3- and 6 months after chemotherapy in high D-dimer group [baseline, 65.2% (62.8–71.4%); 3 months, 62.9% (59.0–67.7%); 6 months, 63.1% (60.0–67.1%); 12 months, 63.3% (58.8–66.0%), p = 0.03], but no change was observed in low D-dimer group. The occurrence of CTRCD within the 12-month follow-up period was higher in the high D-dimer group than in the low D-dimer group (16.2 vs. 4.5%, p = 0.0146). Multivariable logistic regression analysis revealed that high D-dimer level at baseline was an independent predictor of the development of CTRCD [odds ratio 3.93, 95% CI (1.00–15.82), p = 0.047].ConclusionWe should pay more attention to elevated D-dimer levels not only as a sign of cancer-associated thrombosis but also the future occurrence of CTRCD.

Background: Liver function may be a useful indicator of response to cardiac resynchronization therapy (CRT). We aimed to investigate the clinical significance of albumin-bilirubin (ALBI) score, an assessment tool of liver function, on outcomes in heart failure (HF) patients treated with CRT. Methods: We studied 180 patients undergoing CRT. The ALBI score, derived from albumin and total bilirubin, and left ventricular ejection fraction (LVEF) were assessed before and 6 months after CRT. The patients were classified according to the ALBI score before CRT, High (&gt, −2.60) or Low (≤−2.60) ALBI groups. The patients were then reclassified based on the ALBI score before and 6 months after CRT, High/High, High/Low, Low/High, and Low/Low ALBI groups. We evaluated the prognostic value of the ALBI score for HF deaths after CRT. Results: During a median follow-up period of 50 months, there were 41 (22.7%) HF deaths. A Cox proportional hazard analysis revealed that high ALBI scores at baseline were not related to HF deaths (hazard ratio, 1.907, p = 0.068). However, High/High ALBI scores, but not High/Low or Low/High ALBI scores, were an independent predictor of HF deaths compared with Low/Low ALBI scores (hazard ratio, 3.449, p = 0.008), implying that consistently high ALBI scores were associated with poor prognosis. The percentage change in LVEF from baseline to 6 months after CRT did not differ among the four groups, suggesting that left ventricular systolic function was not linked with the ALBI score. Conclusions: ALBI scores before and after CRT are a new indicator of CRT response, and have a predictive value for HF deaths in HF patients.

Background The clinical implications of chronic kidney disease (CKD) and cardiac sympathetic nervous activity (CSNA) regarding lethal arrhythmic events have not yet been fully elucidated in patients with chronic heart failure (CHF). We hypothesized that the combination of CKD and abnormal CSNA, assessed by 123I‐metaiodobenzylguanidine (123I‐MIBG) scintigraphy, may provide useful prognostic information for lethal arrhythmic events. Methods We studied 165 consecutive hospitalized CHF patients without dialysis. Cardiac 123I‐MIBG scintigraphy was performed in a clinically stable condition, and abnormal CSNA was defined as a late heart‐to‐mediastinum ratio of

High-power short-duration (HP-SD) ablation could reduce collateral tissue damage by shortening the conductive heating phase. However, it is difficult to evaluate the transmural effect of ablation lesions during pulmonary vein isolation (PVI) procedures. The present study aimed to evaluate the change in superior vena cava (SVC) potential delay as a surrogate marker of collateral tissue damage during right PVI, which is adjacent to SVC. Out of 250 consecutive patients who underwent PVI, 86 patients in whom SVC potential during sinus rhythm was recorded both before and after right PVI were analyzed. In 46 of the patients, an HP-SD setting of 45–50 W was used (HP-SD group). In the remaining 40 patients, a conventional power setting of 20–30 W was used (conventional group). We compared the change in SVC potential delay after right PVI, radiofrequency energy, and mean contact force in the anterior–superior right PVI line, which was close to the posterior aspect of SVC, between the two groups. Although the total delivered radiofrequency energy (2,924 J vs. 2,604 J) and the mean contact force (18.5 g vs. 16.0 g) in the SVC overlapping area did not differ, the change in SVC potential delay after right PVI was significantly longer in the conventional group compared to the HP-SD group (5.0 ms vs. 0.0 ms, p

Atrial fibrillation (AF) often coexists with atrial septal defects (ASD). Each of the transcatheter closure for ASD and radiofrequency catheter ablation (RFCA) for AF have been established as the first-line therapy. However, there are limited data about therapeutic effect RFCA plus transcatheter ASD closure on AF recurrence in AF patients with ASD. The aim of the current study was to investigate the clinical impact of ASD closure following RFCA on AF recurrence. Forty-two ASD patients (17 males and 54 ± 20 years old) were enrolled and classified into three groups: ASD occlusion-sinus rhythm (ASO-SR) (n = 26), no AF history prior to ASD closure; ASO-AF-RFCA (n = 11), RFCA was performed due to AF history before ASD closure; and ASO-AF-anti-arrhythmic drug (ASO-AF-AAD) (n = 5), AF was treated with AAD before and after ASD closure. AF occurrence among the 3 groups was evaluated. Kaplan-Meier analysis showed that ASO-SR and ASO-AF-RFCA groups showed a lower AF occurrence ratio than ASO-AF-AAD group during the 14- ± 9-month follow-up periods (P = 0.013). AF occurrence in ASO-SR and ASO-AF-RFCA groups was comparable (P = 0.480). Bi-atrial reverse remodeling, such as decrease in left atrial volume index (P = 0.049) and right atrial area (P = 0.046), and significant decrease in high-sensitivity C-reactive protein levels (P = 0.049) were identified in ASO-AF-RFCA group, but not in ASO-AF-AAD group. A combination of two percutaneous therapies was proven to be effective and induced bi-atrial reverse remodeling in association with inflammatory reaction.

Aims: We aimed to assess the associations of CAVI with exercise capacity in heart failure (HF) patients. In addition, we further examined their prognosis.Methods: We collected the clinical data of 223 patients who had been hospitalized for decompensated HF and had undergone both CAVI and cardiopulmonary exercise testing.Results: For the prediction of an impaired peak oxygen uptake (VO2) of < 14 mL/kg/min, receiver-operating characteristic curve demonstrated that the cutoff value of CAVI was 8.9. In the multivariate logistic regression analysis for predicting impaired peak VO2, high CAVI was found to be an independent factor (odds ratio 2.343, P = 0.045). We divided these patients based on CAVI: the low-CAVI group (CAVI < 8.9, n = 145) and the high-CAVI group (CAVI ≥ 8.9, n = 78). Patient characteristics and post-discharge cardiac events were compared between the two groups. The high-CAVI group was older (69.0 vs. 58.0 years old, P < 0.001) and had lower body mass index (23.0 vs. 24.1 kg/m2, P = 0.013). During the post-discharge follow-up period of median 1,623 days, 58 cardiac events occurred. The Kaplan–Meier analysis demonstrated that the cardiac event rate was higher in the high-CAVI group than in the low-CAVI group (log–rank P = 0.004). The multivariate Cox proportional hazard analysis revealed that high CAVI was an independent predictor of cardiac events (hazard ratio 1.845, P = 0.035).Conclusion: High CAVI is independently associated with impaired exercise capacity and a high cardiac event rate in HF patients.

Clinical significance of reduced vagal activity following pulmonary vein isolation (PVI) for atrial fibrillation (AF) remains unclear. Periesophageal vagal nerve injury following PVI may be a powerful contributing factor of decreased vagal tone. Drug‐refractory 51 AF patients (31 males, 64 ± 11 years), who underwent successful PVI, were enrolled. We performed esophagogastroduodenoscopy 2 days after PVI and assessed delayed gastric emptying (DGE). Additionally, the coefficient of variance of R-R interval (CVRR) as a surrogate for vagal tone was measured before PVI, as well as at 1 day and 3 months after PVI. The patients were divided into two groups, patients with DGE and patients without DGE, and changes in CVRR were compared. After PVI, 12 out of 51 patients (23.5%) had DGE. The baseline CVRR did not differ between the patients with (n = 12) and those without (n = 39) DGE (median 3.13%, interquartile range 1.69–5.13 vs. median 3.76%, interquartile range 2.96–5.90, P = 0.297). However, CVRR at 1 day after PVI was significantly lower in the patients with DGE than in those without (median 1.49%, interquartile range 0.90–2.19 vs. median 2.59%, interquartile range 1.58–3.86, P = 0.035), and then CVRR at 3 months became similar between the two groups, suggesting that the two groups had different changes in vagal tone after PVI. The recurrence of AF was similar at 3–6 months after PVI between the two groups. A significantly decreased CVRR immediately after PVI is a sign of DGE incidence, implying collateral damage to the esophagus.

Background: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vasoconstriction and organic stenosis. It has been demonstrated that endothelin-1 (ET-1) induces pulmonary vasoconstriction through the activation of RhoA. In addition, a gene mutation of activin receptor-like kinase (ACVRL)-1 is recognized in PAH patients. However, little is known about the association between ET-1 and ACVRL-1.Objective: In the present study, we aimed to investigate the effect of ET-1 on ACVRL-1 expression and delineate the involvement of the Gi/RhoA/Rho kinase pathway.Methods: ET-1 was added to culture medium of human pulmonary arterial endothelial cells (PAECs). Pre-treatment with pertussis toxin (PTX) or exoenzyme C3 transferase (C3T) was performed for inhibition of Gi or RhoA, respectively. Rho kinase was inhibited by Y27632. Mithramycin A was used for inhibition of Sp-1, which is a transcriptional factor of ACVRL-1. The active form of RhoA (GTP-RhoA) was assessed by pull-down assay.Results: ACVRL-1 expression was increased by ET-1 in the PAECs. Pull-down assay revealed that ET-1 induced GTP-loading of RhoA, which was suppressed by pre-treatment with PTX or C3T. Further, PTX, C3T, and Y27632 suppressed the ET-1-induced ACVRL-1 expression. ET-1 increased the activity of the ACVRL-1 promoter and stabilized the ACVRL-1 mRNA. Sp-1 peaked 15 min after adding ET-1 to the PAECs. PTX and C3T prevented the increase of Sp-1 induced by ET-1. Inhibition of Sp-1 by mithramycin A suppressed ET-1-induced ACVRL-1 upregulation.Conclusion: The present study demonstrated that ET-1 increases ACVRL-1 expression in human PAECs via the Gi/RhoA/Rho kinase pathway with the involvement of Sp-1.

BACKGROUND: The combination of electrical and structural remodeling may have a strong effect on the prognosis of non‐ischemic heart failure (HF). We aimed to clarify whether prolonged PR‐interval and the presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) influence the outcomes of patients with non‐ischemic HF. METHODS: We studied 262 consecutive hospitalized patients with non‐ischemic HF. In a clinically stable condition, a 12‐lead electrocardiogram and CMR were performed, and the clinical characteristics and outcomes were investigated. RESULTS: During the follow‐up of 967.7 ± 851.8 days, there were 68 (25.9%) cardiac events (HF or sudden death, re‐hospitalization due to HF, or ventricular tachyarrhythmias). In a multivariable analysis, a median rate‐adjusted PR (PRa)‐interval of ≥173.5 ms and the presence of LGE were associated with cardiac events with a hazard ratio of 1.690 and 2.045 (p = .044 and p = .006, respectively). Study subjects were then divided into four groups based on long (≥173.5 ms) or short (

Background: Recently, a high-power short-duration (HP-SD) setting has been introduced in atrial fibrillation (AF) ablation. Ablation using this setting reduces collateral tissue damage by shortening the conductive heating phase compared to conventional setting. However, the lesion characteristics have not been rigorously evaluated during ablation procedure. We hypothesized that superior vena cava (SVC) potential could be affected by excessive transmural lesions in anterior-superior right pulmonary vein isolation (PVI), adjacent to posterior aspect of SVC. Therefore, we compared the produced potential delay in SVC between HP-SD and conventional settings. Methods and Results: The consecutive 42 patients (61±10 years, 32 men) who underwent PVI for drug refractory AF were analyzed. Before introduction of HP-SD setting to AF ablation in November 2018, 14 patients underwent right PVI with conventional setting with output of 20-30 W (Conventional group). In the remaining 28 patients after then, right PVI was performed using HP-SD setting with output of 45-50 W (HP-SD group). We compared total radiofrequency energy and mean contact force along the anterior superior right PVI line between the 2 groups. Moreover, the produced SVC potential delay was calculated after anterior superior right PVI and compared between the 2 groups. Total radiofrequency energy delivered (6138 J vs. 6139 J, P = 0.999) and the mean contact force (17.2 g vs. 20.2 g, P = 0.100) in the anterior superior right PV did not differ between the HP-SD and Conventional groups. However, the produced SVC potential conduction delay after anterior superior right PVI was significantly longer in Conventional group compared to HP-SD group (6.2 ms vs. 0.5 ms, P < 0.001). Conclusions: Our data suggest that HP-SD setting caused less collateral tissue damage than conventional setting during PVI. The significant produced SVC potential delay might be a surrogate marker of collateral tissue damage by conductive heating phase in PVI.

Introduction: Cardiomyocyte cell death is closely linked with the pathophysiology of heart failure. Cell-free DNA (cfDNA) is found in circulating blood as fragmented double-strand DNA, which is released from dying cells. However, the clinical significance of cfDNA in heart failure has not been elucidated. Methods and Results: The present study enrolled 32 heart failure patients and 28 control subjects. Circulating cfDNA was isolated from plasma samples in peripheral blood. The levels of total cfDNA assessed by quantitative PCR using LINE1-specific primers were not different between the two groups (P=0.343). Next, cfDNA was subjected to bisulfite conversion to identify cardiomyocyte-derived cfDNA, based on that FAM101A locus is unmethylated in a cardiac-specific manner. Digital PCR targeting the unmethylated FAM101A locus demonstrated that the copy numbers of cardiomyocyte-specific cfDNA were significantly elevated in heart failure patients compared to controls (0.99 [0.77 - 1.98] vs 0 [0 - 0.91] copies/mL, P=0.003, Figure A ). The receiver operating characteristic curve revealed that cardiomyocyte-specific cfDNA significantly discriminated heart failure patients from control subjects (AUC, 0.716, P=0.003). Correlation analysis showed that the levels of cardiomyocyte-specific cfDNA were significantly correlated with serum levels of high-sensitivity cardiac troponin I (r = 0.438, P = 0.012, Figure B ), but not with BNP (r = 0.275, P = 0.058), suggesting that the elevated cardiomyocyte-specific cfDNA might be associated with enhanced cardiomyocyte death but not with high ventricular filling pressure. Conclusions: A newly developed bisulfite-digital PCR system identified an increase in cardiomyocyte-specific cfDNA in heart failure patients. cfDNA may be a novel biomarker to measure the actual numbers of cardiomyocyte death in heart failure.

Objective The relationship between changes in the nutritional status after cardiac resynchronization therapy (CRT) and the prognosis has not been fully elucidated. We aimed to evaluate the changes in the nutritional status as assessed by the prognostic nutritional index (PNI) and their associations with the improvement in the cardiac function and subsequent clinical outcomes. Methods The study population consisted of 119 patients with a CRT-device. They were divided into 2 groups, based on whether their PNI had increased at 6 months after CRT-device implantation (positive ΔPNI group, n=73) or not (negative ΔPNI group, n=46). The left ventricular (LV) end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were measured before and six months after CRT-device implantation. We compared the changes in the cardiac function and prevalence of adverse events (re-hospitalization due to worsening heart failure or all cause death) between the two groups. Results In the positive ΔPNI group, the LVEDV (186±93 mL vs. 149±71 mL, p

Background: Tartrate-resistant acid phosphatase type 5b (TRACP5b) is derived from osteoclasts, and has been used as a marker of osteoporosis (bone resorption). Although heart failure (HF) is associated with catabolic bone remodelling, serum TRACP5b levels have not been rigourously examined in patients with HF. Methods: We conducted a prospective observational study of 688 decompensated HF patients who had been discharged and whose TRACP5b had been measured. These patients were divided into tertiles on the basis of serum TRACP5b levels: first (TRACP5b < 316 mU/dL, n = 229), second (TRACP5b 316-489 mU/dL, n = 229), and third (TRACP5b ≥ 490 mU/dL, n = 230). We compared the patient baseline characteristics, exercise capacity, and their postdischarge prognosis, including cardiac mortality and cardiac events such as cardiac death and worsening HF. Results: Age was significantly higher, and prevalence of female sex and anemia was significantly higher in the third tertile than in the first and second tertiles (P < 0.05, respectively). Circulating TRACP5b levels were correlated with peak breath-by-breath oxygen consumption, but not with left ventricular ejection fraction. In the Kaplan-Meier analysis (mean follow-up, 426 days), cardiac mortality and cardiac event rates progressively increased from the first to the third tertiles (P < 0.05, respectively). In the multivariable Cox proportional hazard analysis, the third tertile was an independent predictor of cardiac mortality and cardiac events (cardiac mortality hazard ratio, 2.493; P = 0.040; cardiac events hazard ratio, 1.687; P = 0.030). Conclusions: High serum levels of TRACP5b, a marker of bone resorption, are associated with high cardiac mortality and cardiac events, accompanied by impaired exercise capacity. Résumé: Introduction: La TRACP5b (de l’anglais, tartrate-resistant acid phosphatase type 5b, soit l’isoforme 5 b de la phosphatase acide résistante au tartrate) qui est dérivée des ostéoclastes a été utilisée comme marqueur de l’ostéoporose (la résorption de l’os). Bien que l’insuffisance cardiaque (IC) soit associée au remodelage osseux catabolique, les concentrations sériques de TRACP5b n’ont pas été rigoureusement examinées chez les patients atteints d’IC. Méthodes: Nous avons mené une étude prospective observationnelle auprès de 688 patients atteints d’IC décompensée qui avaient obtenu leur sortie de l’hôpital et pour lesquels nous avions les mesures de TRACP5b. Nous avons réparti ces patients en tertiles en fonction des concentrations sériques de TRACP5b : le premier (TRACP5b < 316 mU/dL, n = 229), le deuxième (TRACP5b 316-489 mU/dL, n = 229) et le troisième (TRACP5b ≥ 490 mU/dL, n = 230). Nous avons comparé les caractéristiques initiales des patients, leur capacité à l’effort et leur pronostic après la sortie de l’hôpital, à savoir la mortalité d’origine cardiaque et les événements cardiaques tels que la mort cardiaque et l’aggravation de l’IC. Résultats: L’âge était significativement plus élevé, et la prévalence du sexe féminin et de l’anémie était significativement plus élevée dans le troisième tertile que dans les premier et deuxième tertiles (P < 0,05, respectivement). Les concentrations circulantes de TRACP5b corrélaient avec la consommation d’oxygène maximale « respiration par respiration », mais non avec la fraction d’éjection ventriculaire gauche. Dans l’analyse de Kaplan-Meier (durée moyenne de suivi, 426 jours), les taux de mortalité d’origine cardiaque et d’ événements cardiaques augmentaient progressivement du 1er tertile au 3e tertile (P < 0,05, respectivement). Dans l’analyse multivariable selon le modèle des risques proportionnels de Cox, le 3e tertile était un prédicteur indépendant de la mortalité d’origine cardiaque et des événements cardiaques (rapport de risque de mortalité d’origine cardiaque, 2,493; P = 0,040; rapport de risque d’événements cardiaques, 1,687; P = 0,030). Conclusions: Les concentrations sériques élevées de TRACP5b, un marqueur de la résorption de l’os, sont associées à la hausse des taux de mortalité d’origine cardiaque et d’ événements cardiaques, accompagnés de la diminution de la capacité à l’effort.

Background: The mechanism of esophageal thermal injury (ETI; esophageal mucosal injury and periesophageal nerve injury leading to gastric hypomotility) remains unknown when using a high-power short-duration (HP-SD) setting. This study sought to evaluate the characteristics of esophageal injuries in atrial fibrillation ablation using a HP-SD setting. Methods: After exclusion of 5 patients with their esophagus at the right portion of left atrium and 21 patients with additional ablations such as box isolation and low voltage area ablation in left atrium posterior wall, 271 consecutive patients (62±10 years, 56 women) who underwent pulmonary vein isolation by radiofrequency catheter ablation were analyzed. In the 101 patients, a HP-SD setting at 45 to 50 W with an Ablation Index module was used (HP-SD group). In the remaining 170 patients before introduction of the HP-SD setting, a conventional power setting of 20 to 30 W with contact force monitoring was used (conventional group). We performed esophagogastroduodenoscopy after pulmonary vein isolation in all patients and investigated the incidence and characteristics of ETI. Results: Although the incidence of ETI was significantly higher in the HP-SD group compared with the conventional group (37% versus 22%, P =0.011), the prevalence of esophageal lesions did not differ between the groups (7% versus 8%). Multivariate logistic regression analysis revealed that the use of the HP-SD setting (odds ratio, 6.09, P Conclusions: Although the use of the HP-SD setting was a strong predictor of ETI, it could avoid deeper thermal injuries that reach the esophageal mucosal layer.

Background: The predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score predicts the risk of bleeding in patients treated with dual antiplatelet therapy after percutaneous coronary intervention. Although the PRECISE-DAPT score is expected to be useful beyond its original field, long-term prognostic value of this score in patients with acute myocardial infarction (AMI) remains unclear. In the current study, we aimed to investigate the performance of the PRECISE-DAPT score in predicting the long-term prognosis in patients with AMI. Methods and results: Consecutive 552 patients with AMI, who had been discharged from our institution, were enrolled. We divided the patients into three groups, based on their PRECISE-DAPT scores: the low (PRECISE-DAPT

Background The prognostic impact of platelet distribution width (PDW), which is a specific marker of platelet activation, has been unclear in patients with heart failure (HF). Methods and results We conducted a prospective observational study enrolling 1,746 hospitalized patients with HF. Patients were divided into tertiles based on levels of PDW: 1st (PDW < 15.9 fL, n = 586), 2nd (PDW 15.9–16.8 fL, n = 617), and 3rd (PDW ≥ 16.9, n = 543) tertiles. We compared baseline patients’ characteristics and post-discharge prognosis: all-cause death; cardiac death; and cardiac events. The 3rd tertile showed the highest age and levels of B-type natriuretic peptide compared to other tertiles (1st, 2nd, and 3rd tertiles; age, 69.0, 68.0, and 70.0 years old, P = 0.038; B-type natriuretic peptide, 235.2, 171.9, and 241.0 pg/mL, P < 0.001). Left ventricular ejection fraction was equivalent among the tertiles. In the Kaplan-Meier analysis, rates of all endpoints were the highest in the 3rd tertile (log-rank P < 0.001, respectively). The Cox proportional hazard analysis revealed that the 3rd tertile was associated with adverse prognosis (all-cause death, hazard ratio [HR] 1.716, P < 0.001; cardiac death, HR 1.919, P < 0.001; cardiac event, HR 1.401, P = 0.002). Conclusions High PDW is a novel predictor of adverse prognosis in patients with HF.

Background Cardiac amyloidosis (CA) is characterized by left ventricular hypertrophy (LVH) and autonomic nervous imbalance due to amyloid infiltration. However, autonomic dysfunction is often seen in heart failure (HF) with LVH from other etiologies. We aimed to characterize autonomic dysfunction in CA from other etiologies of LVH. Methods Fifty‐five HF patients with LVH (35 males, mean age 65 ± 16 years) were enrolled. LVH was defined as left ventricular mass index measured by echocardiography >95 g/m2 in women and 115 g/m2 in men. The etiology was as follows: amyloid light chain (AL)‐CA, n = 14; hypertrophic cardiomyopathy, n = 21; and aortic stenosis (AS), n = 20. With the patient in a clinically stable condition, heart rate variability (HRV) and heart rate turbulence (HRT), which reflect autonomic dysfunction, were measured using Holter monitoring and compared among the three groups. Results Brain natriuretic peptide levels, LVH severity, left ventricular ejection fraction, and tissue Doppler index E/e′ did not differ among the three groups. However, severe abnormalities of HRV and HRT were obtained in AL‐CA. In the ROC analysis to identify AL‐CA in HF with LVH, the best cutoff value for standard deviation of all R‐R intervals, standard deviation of the 5‐min mean R‐R intervals, turbulence onset, and turbulence slope were 68.5 ms (AUC: 0.865), 58.5 ms (AUC: 0.834), 0.25% (AUC: 0.813), and 1.00 ms/RR (AUC 0.736), respectively. Conclusion Autonomic dysfunction is a hallmark of AL‐CA, and its noninvasive assessment by Holter monitoring may be a useful tool for differential diagnosis of HF with LVH.

Background The prevalence of depression and/or anxiety disorders is reported to be higher in patients with heart failure ( HF ) than in the general population, and patients with HF also have coexisting cognitive problems. Recently, the development of near‐infrared spectroscopy ( NIRS ) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex, with a high time resolution. The aim of the current study was to determine the associations between frontal brain activity and depressive symptoms, anxiety status, and cognitive function in patients with HF . Methods and Results We measured and compared frontal brain activity determined by NIRS during a verbal fluency task in patients with HF (n=35) and control subjects (n=28). The Center for Epidemiologic Studies Depression Scale for assessment of depressive symptoms, State‐Trait Anxiety Inventory for assessment of anxiety status, Mini‐Mental State Examination for assessment of cognitive function, and NIRS were simultaneously conducted. NIRS showed that frontal brain activity was significantly lower in the HF group than in the control subjects (28.5 versus 88.0 mM·mm; P R =−0.228, P =0.046), Mini‐Mental State Examination ( R =0.414, P =0.017), and verbal fluency task ( R =0.338, P =0.007), but not with Center for Epidemiologic Studies Depression Scale ( R =−0.160, P =0.233). Conclusions Frontal brain activity assessed by NIRS is reduced and is associated with high anxiety status and low cognitive function in patients with HF .

Aim: We aimed to evaluate the significance of the cardio-ankle vascular index (CAVI) to predict stroke in patients with heart failure (HF). Methods: This was a prospective observational study, which recruited clinical data from a total of 557 patients who had been hospitalized for HF and undergone CAVI. According to the receiver operating characteristic curve analysis, the accurate cut-off value of CAVI in predicting post-discharge stroke was 9.64. We divided the patients into two groups: the high-CAVI group (HF patients with CAVI ≥ 9.64, n =111, 19.9%) and the low-CAVI group (HF patients with CAVI ＜9.64, n =446, 80.1%). We compared the patients’ characteristics and post-discharge prognosis. The primary endpoint was stroke. Results: The high-CAVI group was older (73.0 vs. 65.5 years old, P ＜0.001). Male sex (73.9% vs. 61.4%, P =0.015), coronary artery disease (47.7% vs. 36.1%, P =0.024), and diabetes mellitus (54.1% vs. 37.4%, P =0.001) were more prevalent in the high-CAVI group. In contrast, there was no difference in left ventricular ejection fraction, and prevalence of hypertension and dyslipidemia. The Kaplan-Meier analysis demonstrated that post-discharge stroke rate was higher in the high-CAVI group than in the low-CAVI group (log-rank P =0.005). In multivariate Cox proportional hazard analysis, high CAVI was found to be an independent predictor of stroke, with an adjusted hazard ratio of 3.599, compared to low CAVI. Conclusion: CAVI independently predicts stroke in patients with HF.

Transmural thermal injury (TTI), such as esophageal erosion/ulcer and periesophageal nerve injury leading to gastric hypomotility, is not rare complications associated with pulmonary vein isolation (PVI). However, the mechanism and predicting factors of TTI have not yet been fully elucidated with second-generation cryoballoon (CB) PVI. One hundred ten consecutive patients, who underwent CB PVI for atrial fibrillation and received esophagogastroduodenoscopy 2 days later, were investigated. The relationships between TTI and both clinical and anatomical parameters were examined. We measured the following parameters based on the computed tomography data: the angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao angle); the branching angle of the left inferior pulmonary vein (LIPV) to the coronal plane (LIPV angle); and the minimum distance between the LA posterior wall and descending Ao enclosing the esophagus (LA-Ao distance). TTIs occurred in 19 patients (esophageal erosion in 2 and gastric hypomotility in 17). The patients with TTI were significantly older than those without TTI. In the anatomical parameters, the LIPV angle was larger and the LA-Ao distance was shorter in the TTI (+) group compared to the TTI (−) group. With the multivariate logistic regression analysis, the age (odds ratio [OR] 2.148, P = 0.022) and LA-Ao distance (OR 0.430, P = 0.013) were independent predictors of TTI. The occurrence of TTI in CB PVI was associated with aging, suggesting compromised periesophageal circulation, and the anatomical proximities between the LA and the descending Ao, which enclose the esophagus.

Background Patients with some mutations in the lamin A/C (LMNA) gene are characterized by the presence of dilated cardiomyopathy (DCM), conduction abnormalities, ventricular tachyarrhythmias (VT), and sudden cardiac death (SCD). Various clinical features have been observed among patients who have the same LMNA mutation. Here, we show a family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, and a family history of conduction disorder, DCM, VT, and SCD. Case presentation A proband (female) with atrial fibrillation and bradycardia was implanted with a pacemaker in her fifties. Twenty years later, she experienced a loss of consciousness due to polymorphic VT. She had a serious family history; her mother and elder sister died suddenly in their fifties and sixties, respectively, and her nephew and son were diagnosed as having DCM. Genetic screening of the proband, her son, and nephew identified a nonsense mutation (c.475G > T, p.E159*) in the LMNA gene. Although the proband’s left ventricular ejection fraction remained relatively preserved, her son and nephew’s left ventricular ejection fraction were reduced, resulting in cardiac resynchronization therapy by implantation of a defibrillator. Conclusions In this family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, DCM, SCD, and malignant VT occurred. Clinical manifestation of various atrial and ventricular arrhythmias and heart failure with reduced ejection fraction occurred in an age-dependent manner in all family members who had the nonsense mutation. It appears highly likely that the E159* LMNA mutation is related to various cardiac problems in the family of the current report.

BACKGROUND Heart failure (HF) patients have a higher risk of recurrent HF and cardiac death, and electrical remodeling is considered to be an important factor for HF progression. The present study aimed to validate the utility of electrocardiogram and Holter monitoring for the risk stratification of HF patients. METHODS Our study comprised 215 patients (144 males, mean age 62 years) who had been hospitalized due to acute decompensated HF. Electrocardiogram (QRS duration and QTc interval) and 24-hour Holter monitoring (heart rate variability, heart rate turbulence, and T-wave alternans [TWA]) were performed in stable condition before discharge. The clinical characteristics and outcomes were then investigated. RESULTS During a median follow-up period of 2.7 years, there were 83 (38.6%) cardiac events (rehospitalization due to worsening HF [n = 51] or cardiac death [n = 32]). The patients with cardiac events had a lower turbulence slope (TS) and higher TWA compared to those without cardiac events (TS, 3.0 ± 5.5 ms/RR vs. 5.3 ± 5.6 ms/RR, P = 0.001; TWA, 66.1 ± 19.6 μV vs. 54.7 ± 15.1 μV, P

Background To investigate the impact of uncontrolled blood pressure (BP) on left atrial (LA) remodeling and clinical outcome after pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (AF). Methods One hundred and one symptomatic paroxysmal AF patients (85 males, 62.2 ± 8.4-year-old) who underwent successful PVI were classified as follows: group 1 (n = 46), no hypertension (HTN); group 2 (n = 36), HTN with controlled BP; and group 3 (n = 19), HTN with uncontrolled BP. Uncontrolled BP was defined as BP > 140/90 mm Hg. LA dimension was measured by echocardiography before and 6 months after PVI. LA wall thickness along the ablation line was measured using computed tomography prior to PVI. Cox regression analysis was performed for the prediction of recurrence. Results LA wall thickness in groups 2 and 3 was greater than that of group 1, except for the anterior right superior pulmonary vein (PV) and posterior left inferior PV. Kaplan-Meier analysis revealed a significantly higher recurrence in group 3 (52.6%). LA dimension only increased in group 3 (38.2 ± 5.6 mm to 41.3 ± 6.2 mm, P = 0.022). At the second procedure, all group 3 recurrent patients showed substrate degradation (low voltage area and/or dense scar formation) and required substrate modification. Uncontrolled BP was an independent risk factor for recurrence (hazard ratio: 2.350, P = 0.033). Conclusions HTN induced heterogeneous LA hypertrophy regardless of whether HTN was controlled. Uncontrolled BP promoted atrial remodeling, and is therefore a strong predictor for recurrence of AF after PVI.

Objectives: The uric acid (UA) level is related to cardiac events and mortality, but little is known about the clinical significance of serum UA with regard to the ventricular tachyarrhythmia (VT) risk in patients with heart failure. Methods: The present study enrolled 56 patients with ischemic and nonischemic cardiomyopathy (37 males, mean age 64.7 ± 11.1 years) who received prophylactic implantable cardioverter-defibrillator (ICD) implantation. Based on a median serum UA value, study subjects were divided into two groups: serum UA < 6.1 mg/dL (group L, n = 29) and ≥6.1 mg/dL (group H, n = 27). Echo- and electrocardiograms (QRS duration and QTc intervals) were examined in each group. Results: During the follow-up period (30 ± 8 months), 22 (39%) patients had appropriate ICD therapies for sustained VT. There was no significant difference in the electro- and echocardiographic data between both groups. However, appropriate ICD therapies were significantly higher in group H than in group L (p = 0.02). In multivariate analysis, UA was an independent predictor of appropriate ICD therapies (hazard ratio 1.826, 95% confidence interval 1.248–2.671, p = 0.002). Conclusions: Serum UA levels might be a predictor of VT, providing new aspects regarding the decision to adapt ICD implantation in patients with heart failure.

AIM To explore changes in left ventricular (LV) function and the relationship of these changes with myocardial blood flow (MBF) evaluated by 13N-ammonia hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) during vasodilator stress in patients with suspected coronary artery disease (CAD). MATERIALS AND METHODS Fifty-two consecutive patients with suspected CAD, who underwent 13N-ammonia PET/MRI, were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. MBF and coronary flow reserve (CFR) were calculated from dynamic acquisition of 13N-ammonia PET. LV function was evaluated by MRI both at rest and during vasodilator stress. An abnormal perfusion on myocardial images was defined as a summed difference score of ≥4. RESULTS MRI showed that the LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction (LVEF) remained unchanged during vasodilator stress in all patients (n=52) as well as in the patients with CFR of 5% during vasodilator stress. In these four patients, CFR was lower (1.57 ± 0.12 versus 2.18 ± 0.86, p CONCLUSION The LV volume and systolic function evaluated by cardiac MRI remained unchanged during vasodilator stress; however, LV dysfunction during vasodilator stress may occur in patients with severe CAD.

Aims Transmural thermal injury (TTI), such as oesophageal erosion/ulcer and perioesophageal nerve injury leading to gastric hypomotility, is an important complication associated with pulmonary vein isolation (PVI). However, a predictor of TTI concerning anatomical structures surrounding the oesophagus has not yet been fully elucidated. Therefore, we sought to identify the predisposing factors of TTI after PVI. Methods and results Consecutive 110 patients, who underwent PVI for atrial fibrillation, received oesophagogastroduodenoscopy 2 days later, were investigated. The relationships between TTI and clinical and anatomical parameters were examined. Based on the computed tomography data, we measured the angle of the left atrial (LA) posterior wall to the descending aorta (Ao) (LA-Ao angle), the branching angle of the left inferior pulmonary vein (LIPV) to the coronal plane (LIPV angle), and the minimum distance between the LA posterior wall and descending Ao enclosing the oesophagus (LA-Ao distance). Transmural thermal injuries occurred in 21 patients (oesophageal erosion in 5 and gastric hypomotility in 16). Age, gender, body mass index, LA diameter, and LA volume index in echocardiography were not associated with TTI. However, the LIPV angle was larger and the LA-Ao distance was shorter in the TTI (+) group compared to the TTI (-) group. With multivariate logistic regression analysis, the LIPV angle [odds ratio (OR): 2.144, P = 0.0031] and LA-Ao distance (OR: 0.392, P = 0.0229) were independent predictors of TTI. Conclusion The anatomical proximities of the LA posterior wall, LIPV, and descending Ao surrounding the oesophagus are strongly associated with the prevalence of TTI.

Intrathoracic impedance measured by cardiac resynchronization therapy (CRT) varies because several factors other than pulmonary congestion may affect this parameter. Therefore, we hypothesized that changes in intracardiac impedance between the right and left ventricular leads would be more accurate to identify worsening heart failure in patients with CRT. The study enrolled 21 patients with CRT defibrillator (15 males, 70 ± 12 years). During the follow-up period (12 ± 7 months), the subjects experienced 37 fluid index threshold (60 ohm-days) crossing events. These events were divided into two groups whether hospitalization due to worsening heart failure was required (group-H, n = 14) or not (group-NH, n = 23). Based on the intracardiac impedance at the beginning of increasing fluid index (BI) and the crossing of 60 ohm-days (CI), the rate of impedance change (BI–CI/BI) was estimated. Then, the time elapsed from BI to CI (T) was evaluated. We calculated the rate of intracardiac impedance change per day (BI–CI/BI × T) in each group. The rate of intrathoracic impedance change per day was also determined using the same method. The median rate of intracardiac impedance change per day was 0.27 (IQR 0.22–0.54) %/day in group-H, and 0 (IQR 0–0.08) %/day in group-NH with a significant difference (P

We investigated clinical significance of cell-free DNA (cfDNA) in heart failure. This study enrolled 32 heart failure patients and 28 control subjects. Total cfDNA levels were not different between groups (P = 0.343). Bisulfite-digital polymerase chain reaction using the unmethylated FAM101A locus demonstrated that cardiomyocyte-specific cfDNA was significantly elevated in heart failure patients compared with control subjects (median 0.99 [interquartile range 0.77-1.98] vs 0 [0-0.91] copies/mL; P = 0.003). Cardiomyocyte-specific cfDNA significantly discriminated heart failure patients from control subjects (area under the receiver operating characteristic curve, 0.716; P = 0.003) and was positively correlated with troponin I (r = 0.438; P = 0.003) but not with B-type natriuretic peptide (r = 0.275; P = 0.058). cfDNA may be a novel biomarker to measure cardiomyocyte death in heart failure.

Few reports exist regarding the details of ice formation on second-generation cryoballoon (CB) surface during pulmonary vein isolation (PVI). We propose a new parameter “temperature drop” in thawing phase for predicting sufficient ice formation and CB-PVI outcome. Consecutive 106 patients who underwent successful CB-PVI for atrial fibrillation (AF) were analyzed. We defined “temperature drop” as a temperature drop of more than 3 °C just after CB catheter bending. We compared the previously known parameters predicting durable PVI between PVs with or without temperature drop. Then, we compared the PVI outcome among three groups: group 1 with temperature drop in all PVs, group 2 with temperature drop in 1–3 PVs, and group 3 without temperature drop in any PV. Temperature drop was present in 206 out of 424 isolated PVs. In those, PV occlusion score was significantly higher (3.7 ± 0.5 vs. 3.5 ± 0.6, P

Background: Acetoacetate is used as an alternative energy source in the heart, and has the potential to improve cardiac function. However, the prognostic impact of acetoacetate has not been investigated in heart failure. Methods: This study enrolled consecutive 615 hospitalized patients with heart failure. We investigated the associations between circulating acetoacetate and clinical characteristics or prognosis in HF patients. Results: We divided the patients into two groups based on circulating acetoacetate levels (high group: acetoacetate ≥35 µmoL/L, n = 313; and low group: acetoacetate

Background Takayasu arteritis is a rare systemic vasculitis, which affects the aorta and its major branches, especially in young females. Diagnosis and treatment for Takayasu arteritis with coronary stenosis are important to prevent fatal complications. Immunosuppressive treatment such as corticosteroid is a common treatment for this condition. However, the effects of immunosuppressive treatment on inflammatory coronary stenosis caused by Takayasu arteritis remains unknown. Case presentation An 18-year-old female had chest oppression on effort and was referred to our hospital due to ST-segment depression in I, aVL, and V2–4 on electrocardiogram. Coronary angiography showed severe stenosis in the ostium of both the left main trunk and the right coronary artery. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed isolated inflammation of the aortic root. She was diagnosed with Takayasu arteritis and treated with combined immunosuppressive treatment with corticosteroid and tocilizumab, which decreased the FDG uptake in the aortic root. Four months after initiation of the immunosuppressive treatment, coronary angiography showed regression of the coronary ostial stenosis. Coronary artery bypass surgery was considered, but the patient rejected invasive revascularization for coronary artery disease. She did not have chest oppression or ST-segment depression after the immunosuppressive treatment. She had no cardiac events for 6 months after discharge. Conclusions We described regressed coronary ostial stenosis in a young female patient with Takayasu arteritis. Immunosuppressive treatment might have a favorable effect on coronary ostial stenosis in Takayasu arteritis.

Circumferential pulmonary vein (PV) isolation has been widely accepted for catheter ablation in patients with atrial fibrillation (AF). Dissociated PV activity might appear after PV isolation (PVI). However, little is known of dissociated PV activity. This study aimed to reveal the electrophysiological properties and clinical implications of dissociated PV activity. The study subjects were 52 patients (62 ± 7 years, 38 men) who underwent PVI for AF. Electrophysiological properties of the left atrium (LA) and PVs during and after PVI were investigated. Out of 181 targeted PVs, 177 with successful isolation were analyzed. Dissociated PV activity appeared in 14 PVs (8 %) in 12 patients (23 %) after PVI; from the left superior PV in eight, right superior PV in five, and left inferior PV in one. The mean cycle length of dissociated PV activity was 4277 ± 2565 ms. The presence of AF prior to achieving PVI was significantly higher in PV without dissociated PV activity (105 out of 163, 64 %) than in PV with dissociated PV activity (five out of 14, 36 %, P = 0.03). The observed dissociated PV activity was enhanced (new appearance or reduced cycle length) by isoproterenol and suppressed by pacing within the isolated PV. Dissociated PV activity, although influenced by uncertain factors such as overdrive suppression and autonomic situations, would be an indicator of LA-PV bidirectional block and might not be the target of additional ablation after PVI.

The relationship between insulin resistance and atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) remains unclear.Drug-refractory 114 paroxysmal AF patients (89 males, 62 ± 8 years) who underwent successful PVI were enrolled. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and a value of ≥2.5 was defined as insulin resistant. The left atrial volume index (LAVI) was measured using echocardiography before and 1 year after PVI. Tumor necrosis factor-α (TNF-α) and TGF-β1 serum levels were measured before PVI, and the left atrium (LA) conduction velocity was calculated. The patients were divided into two groups (group 1: HOMA-IR 2.5, n = 81; group 2: HOMA-IR ≥ 2.5, n = 33).The LAVI between the two groups before PVI did not significantly differ (P 0.05), nor did TNF-α (7.7 ± 2.0 vs 7.5 ± 1.0 pg/mL; P = 0.149) or TGF-β1 (28.4 ± 12.0 vs 27.6 ± 10.3 ng/mL; P = 0.757). LAVI before and 1 year after PVI in each group did not change. The conduction velocity of group 2 was slower than that of group 1 (0.7 ± 0.1 vs 1.1 ± 0.3 m/s, P 0.001). Kaplan-Meier analysis showed significantly higher AF recurrence in group 2 than that in group 1 ( P = 0.019). Cox multivariable analysis revealed that insulin resistance was an independent predictor of recurrence (hazard ratio 1.287, P = 0.004).Our results suggest that insulin resistance promotes LA electrical remodeling and might be related to AF recurrence after PVI.

Background Pulmonary hypertension (PH) is a common complication of chronic respiratory disease. Recent studies have reported diabetes mellitus (DM) to be a poor prognostic factor in patients with chronic respiratory disease, including chronic obstructive pulmonary disease or interstitial pneumoniae. However, the association between DM and PH in chronic respiratory disease remains unclear. In this study, we aimed to investigate whether DM is a predictor of PH in patients with chronic respiratory disease. Methods We prospectively analyzed 386 patients in our hospital with chronic respiratory disease. An echocardiographic pressure gradient between the right atrium and the right ventricle of ≥ 40 mmHg was defined as PH. We compared the clinical characteristics and impact of DM between chronic respiratory disease patients with and those without PH. Results Of the 386 patients, 42 (10.9%) were diagnosed as having PH. The PH group had higher modified medical research council (mMRC) grade and complication rate of DM, but not hypertension and hyperlipidemia, when compared to the non-PH group. Multivariable logistic regression analysis revealed that mMRC scale (odds ratio 1.702, 95% confidence interval, 1.297 to 2.232, P < 0.001) and presence of DM (odd ratio 2.935, 95% confidence interval, 1.505 to 5.725, P = 0.002) were associated with PH in chronic respiratory disease patients. Conclusion DM is potentially associated with PH and is an independent factor for prediction of PH in patients with chronic respiratory disease.

Both conventional radiofrequency catheter ablation (RFCA) and cryoballoon ablation (CBA) have been widely accepted as a treatment for atrial fibrillation. Esophageal erosion/ulcer is important in catheter ablation of atrial fibrillation because it has a potential to advance to left atrial-esophagus

Background: Recent studies have shown that high levels of serum phosphate are associated with adverse cardiovascular events. However, little is known about the relation between phosphate levels and improvement of cardiac function in chronic heart failure (CHF) patients who underwent cardiac resynchronization therapy (CRT). The purpose of this study was to examine whether serum phosphate levels were able to predict responders to CRT and adverse cardiac events. Methods: The study population consisted of 30 CHF patients (24 males, mean age 65.7±8.5 years) who received CRT with defibrillator (CRT-D) implantation. Levels of serum phosphate were measured before, and 6 months after, CRT-D implantation. Left ventricular end-diastolic volume and end-systolic volume were assessed simultaneously by echocardiography. In addition, the rate of re-hospitalization due to worsening of heart failure was investigated. All patients were divided into 2 groups: responders (Group-R, n=18) and non-responders (Group-NR, n=12) to CRT-D. Responders were defined as patients who showed >15% reduction in left ventricular end-systolic volume. We compared these parameters between the 2 groups. Results: Serum phosphate levels were significantly lower in Group-R than in Group-NR (3.3±0.2 vs. 3.7±0.4 mg/dL, p=0.01). The rate of re-hospitalization was lower in Group-R than in Group-NR (0% vs. 33%, p=0.018). Multivariate analysis showed that serum phosphate levels had a predictive power to determine responders to CRT (odds ratio 0.008, 95% confidence interval 0.000–0.348, p=0.015). Conclusions: These results suggest that serum phosphate levels might predict both responders to CRT, and adverse cardiac events, in CHF patients with CRT-D.