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Abstract Malnutrition is classified into marasmus and kwashiorkor in children. However, the clinical significance of these aspects is unclear in adult patients with heart failure (HF). We divided 2308 adult patients with HF into four groups according to marasmus type (body mass index

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type 2 diabetes; however, their effect on arrhythmias is unclear. The purpose of this study was to investigate the effects of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes. Methods A total of 150 patients with type 2 diabetes who were treated with an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) were randomized to once-daily empagliflozin or placebo for 24 weeks. The primary endpoint was the change in the number of ventricular arrhythmias from the 24 weeks before to the 24 weeks during treatment. Secondary endpoints included the change in the number of appropriate device discharges and other values. Results In the empagliflozin group, the number of ventricular arrhythmias recorded by ICD/CRT-D decreased by 1.69 during treatment compared to before treatment, while in the placebo group, the number increased by 1.79. The coefficient for the between-group difference was − 1.07 (95% confidence interval [CI] − 1.29 to − 0.86; P

Abstract Background The relationship between liver fibrosis and left atrial (LA) remodeling in atrial fibrillation (AF) remains uncertain. We examined the associations between the fibrosis‐4 (FIB4) index, an indicator of liver fibrosis, and both LA low‐voltage areas (LVAs) on electroanatomic mapping and AF recurrence postablation. Methods We recruited 343 patients who underwent radiofrequency catheter ablation (RFCA) or cryoballoon ablation (CBA) for AF. First, the association between the FIB4 index and LA LVAs (5 cm2) compared to those without. Additionally, the quantitative size of LVAs showed a positive correlation with the FIB4 index (R = .642, p

Abstract Background This study thought to elucidate the anatomical features that can predict an epicardial connection (EC) between the right pulmonary vein (RPV) and right atrium. Methods We retrospectively analyzed 251 consecutive patients undergoing initial radiofrequency pulmonary vein isolation. We defined EC as present when RPV could not be isolated with circumferential ablation and additional ablation for the conduction gap if needed, and RPV isolation could be achieved by ablation for the earliest activation site >10 mm inside the initial ablation line. Using computed tomography data, we evaluated the RPV bifurcation angle, and the area occupation ratio of the carina region to the RPV antrum (ARC) for predicting EC. In subjects with EC undergoing RPV activation mapping after circumferential ablation, the correlation between conduction delay and bipolar/unipolar potential voltage in the carina region was investigated. Results There were ECs in 45 out of 251 patients (17.9%). The RPV bifurcation angle (47.7° vs. 38.8°, p

Abstract Although the prevalence of cognitive impairment and depression is higher in patients with atrial fibrillation (AF) than in the general population, the mechanism has not been fully examined and impact of catheter ablation (CA) of AF also remains unclear. 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. We assessed brain activities by NIRS, depressive symptoms by the Center for Epidemiologic Studies Depression Scale (CES-D) and cognitive function by Mini-Mental State Examination (MMSE). We then compared the results between AF patients (paroxysmal AF n = 18 and persistent AF n = 14) and control subjects (n = 29). Next, we also followed up persistent AF patients who kept sinus rhythm at 3 months after CA (n = 8) and measured their brain activities using NIRS, CES-D and MMSE after CA to investigate the associations of changes in brain activities with changes in both CES-D and MMSE. Our results showed that (1) frontal and temporal brain activities were lower in patients with persistent AF than both in control subjects and paroxysmal AF patients (P

Abstract Purpose The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF). Methods We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20–35 W) in 73 patients (Conventional group) and using the HP-SD setting (45–50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups. Results The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P

Abstract Background It 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. Methods We 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. Results The 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. Conclusions The results suggest that metabolic disorder may suppress pulmonary artery reverse remodeling in mice with hypoxia-induced PH during reoxygenation.

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.

Abstract 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

BackgroundIt has been recently reported that the renal venous stasis index (RVSI) assessed by renal Doppler ultrasonography provides information to stratify pulmonary hypertension that can lead to right-sided heart failure (HF). However, the clinical significance of RVSI in HF patients has not been sufficiently examined. We aimed to examine the associations of RVSI with parameters of cardiac function and right heart catheterization (RHC), as well as with prognosis, in patients with HF.MethodsWe performed renal Doppler ultrasonography, echocardiography and RHC in hospitalized patients with HF (n = 388). RVSI was calculated as follows: RVSI = (cardiac cycle time-venous flow time)/cardiac cycle time. The patients were classified to three groups based on RVSI: control group (RVSI = 0, n = 260, 67%), low RVSI group (0 < RVSI ≤ 0.21, n = 63, 16%) and high RVSI group (RVSI > 0.21, n = 65, 17%). We examined associations of RVSI with parameters of cardiac function and RHC, and followed up for cardiac events defined as cardiac death or worsening HF.ResultsThere were significant correlations of RVSI with mean right atrial pressure (mRAP; R = 0.253, P < 0.001), right atrial area (R = 0.327, P < 0.001) and inferior vena cava diameter (R = 0.327, P < 0.001), but not with cardiac index (R = −0.019, P = 0.769). During the follow-up period (median 412 days), cardiac events occurred in 60 patients. In the Kaplan–Meier analysis, the cumulative cardiac event rate increased with increasing RVSI (log-rank, P = 0.001). In the multivariate Cox proportional hazard analysis, the cardiac event rate was independently associated with RVSI (high RVSI group vs. control group: hazard ratio, 1.908; 95% confidence interval, 1.046–3.479, P = 0.035).ConclusionRVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.

Abstract 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.

Abstract 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

Abstract 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

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.

BackgroundA 12-lead electrocardiogram (ECG) and Holter ECG have been established as gold standards for detection of arrhythmias. Recently, wearable ECG monitoring devices have been available. Our purpose of the present study was to investigate whether a novel wearable electrode embedded in an undershirt is useful for ECG monitoring and detection of arrhythmias.MethodsWe studied 31 consecutive hospitalized patients who underwent catheter ablation of tachyarrhythmias. Patients equipped a wearable electrode and a lead CM5 of Holter ECG simultaneously, and total heart beats, maximum heart rate (HR), mean HR, minimum HR, detections of arrhythmias, such as atrial fibrillation, non-sustained ventricular tachycardia, and premature ventricular contractions (Lown's grade >II), were compared between the two methods using a Holter ECG analysis software.ResultsMedian recording time of ECG by wearable electrodes was 12.6 hours. Strong correlations between the two methods were observed in total heart beats (R = 0.999, P II (five events) were concordant in two methods. In addition, there were no significant difference in parameters of time-domain and frequency-domain analyses of heart rate variability between the two methods.ConclusionsThe usefulness of a novel electrode embedded in an undershirt is equivalent to that of a Holter ECG in monitoring the ECG and detection of arrythmias.

Abstract 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 Blood‐based DNA methylation patterns are linked to types of diseases. FKBP prolyl isomerase 5 (FKBP5), a protein cochaperone, is known to be associated with the inflammatory response, but the regulatory mechanisms by leukocyte FKBP5 DNA methylation in patients with dilated cardiomyopathy (DCM) remain unclear. Methods and Results The present study enrolled patients with DCM (n=31) and age‐matched and sex‐matched control participants (n=43). We assessed FKBP5 CpG (cytosine‐phosphate‐guanine) methylation of CpG islands at the 5′ side as well as putative promoter regions by methylation‐specific quantitative polymerase chain reaction using leukocyte DNA isolated from the peripheral blood. FKBP5 CpG methylation levels at the CpG island of the gene body and the promoter regions were significantly decreased in patients with DCM. Leukocyte FKBP5 and IL‐1β (interleukin 1β) mRNA expression levels were significantly higher in patients with DCM than in controls. The protein expressions of DNMT1 (DNA methyltransferase 1) and DNMT3A (DNA methyltransferase 3A) in leukocytes were significantly reduced in patients with DCM. In vitro methylation assay revealed that FKBP5 promoter activity was inhibited at the methylated conditions in response to immune stimulation, suggesting that the decreased FKBP5 CpG methylation was functionally associated with elevation of FKBP5 mRNA expressions. Histological analysis using a mouse model with pressure overload showed that FKBP5‐expressing cells were substantially infiltrated in the myocardial interstitium in the failing hearts, indicating a possible role of FKBP5 expressions of immune cells in the cardiac remodeling. Conclusions Our findings demonstrate a link between specific CpG hypomethylation of leukocyte FKBP5 and DCM. Blood‐based epigenetic modification in FKBP5 may be a novel molecular mechanism that contributes to the pathogenesis of DCM.

Abstract 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.

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.

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: Red blood cell distribution width (RDW) is associated with prognosis in widespread cardiovascular fields, but little is known about relationship with the onset of cancer therapeutics-related cardiac dysfunction (CTRCD).Objectives: The purpose of this study was to assess whether RDW could predict the onset of CTRCD by anthracycline.Methods: Consequential 202 cancer patients planed for anthracycline treatment were enrolled and followed up for 12 months. The patients were divided into 2 groups based on the median value of baseline RDW before chemotherapy [low RDW group, n = 98, 13.0 [12.6–13.2]; high RDW group, n = 104, 14.9 [13.9–17.0]]. Cardiac function was assessed serially by echocardiography at baseline (before chemotherapy), as well as at 3, 6, and 12 months after chemotherapy with anthracycline.Results: Baseline left ventricular end systolic volume index and ejection fraction (EF) were similar between two groups. After chemotherapy, EF decreased at 3- and 6-month in the high RDW group [baseline, 64.5% [61.9–68.9%]; 3-month, 62.6% [60.4–66.9%]; 6-month, 63.9% [60.0–67.9%]; 12-month, 64.7% [60.8–67.0%], P = 0.04], but no change was observed in low RDW group. The occurrence of CTRCD was higher in high RDW group than in low RDW group (11.5 vs. 2.0%, P = 0.008). When we set the cut-off value of RDW at 13.8, sensitivity and specificity to predict CTRCD were 84.6 and 62.0%, respectively. Multivariable logistic regression analysis revealed that baseline RDW value was an independent predictor of the development of CTRCD [odds ratio 1.390, 95% CI [1.09–1.78], P = 0.008]. The value of net reclassification index (NRI) and integrated discrimination improvement (IDI) for detecting CTRCD reached statistical significance when baseline RDW value was added to the regression model including known risk factors such as cumulative anthracycline dose, EF, albumin, and the presence of hypertension; 0.9252 (95%CI 0.4103–1.4402, P < 0.001) for NRI and 0.1125 (95%CI 0.0078–0.2171, P = 0.035) for IDI.Conclusions: Baseline RDW is a novel parameter to predict anthracycline-induced CTRCD.

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 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

BackgroundThe 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 resultsWe 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).ConclusionsHigh PDW is a novel predictor of adverse prognosis in patients with HF.

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: Several studies reported that cavotricuspid isthmus-dependent atrial flutter (typical AFL) frequently coexists with atrial fibrillation (AF); however, the underlying mechanisms have not been fully investigated. This study aimed to reveal the mechanisms of the initiation of typical AFL and the association between typical AFL and AF. Methods: Among 154 consecutive patients undergoing a first catheter ablation of AF, we investigated the appearance and mechanism of spontaneous initiation of typical AFL during catheter ablation. Then, we retrospectively investigated 67 consecutive patients without a previous AF episode who underwent typical AFL ablation. The occurrence and predictors of AF after catheter ablation were evaluated. Results: During AF ablation, spontaneous initiation of typical AFL occurred during sinus rhythm in eight (5.2%) patients. The initiations of typical AFL were pulmonary vein (PV) firings except in one patient, in whom paroxysmal AF following superior vena cava firing initiated reverse typical AFL after PV isolation. After typical AFL ablation, AF occurred in 23 (34.3%) patients (mean follow up, 28.2±20.3 months). Kaplan-Meier analysis showed the occurrence of AF after typical AFL ablation to be significantly higher in the patients with a larger left atrial diameter over 40 mm (log-rank test, P=0.046). Conclusions: PV firing through AF played an important role in initiating typical AFL. The occurrence of AF after typical AFL ablation was high, and a dilated left atrium was associated with increased occurrence of AF. These findings disclosed the close relationship between typical AFL and AF, especially PV firing.

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.

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.

Background: T-wave alternans is useful for predicting the occurrence of ventricular tachyarrhythmias and sudden cardiac death in various heart diseases. However, little is known about the clinical significance of T-wave alternans measurement in survivors of ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT). Methods: We studied 28 patients with organic heart disease who survived VF or hemodynamically unstable VT (20 males, mean age 63 years). Echocardiography, electrocardiogram (QRS duration and QTc intervals), and Holter monitoring (heart rate variability, heart rate turbulence and T-wave alternans) were performed before implantable cardioverter-defibrillator (ICD) implantation. Positive T-wave alternans was defined as >65 μV. During the follow-up period (10.2±6.2 months), ventricular tachyarrhythmias requiring appropriate shock therapy occurred in eight patients (29%). The subjects were divided into two groups, based on whether appropriate shock therapy was required (n=8, Group A) or not (n=20, Group B). Parameters from echocardiography, electrocardiogram, and Holter monitoring were compared between the two groups in order to investigate their relationship with the incidence of shock therapy after ICD implantation. Results: The prevalence of positive T-wave alternans was significantly higher in Group A than in Group B (88% vs. 15%, P=0.004). Univariate Cox proportional hazard analysis showed that, among the variables measured, only T-wave alternans had predictive power for recurrent ventricular tachyarrhythmias (hazard ratio, 13.17; 95% confidence interval: 1.606–108.1, P=0.016). Conclusions: These results suggest that T-wave alternans by Holter monitoring is useful for predicting recurrent ventricular tachyarrhythmias in survivors of VF or hemodynamically unstable VT.

Placement of an implantable cardioverter–defibrillator (ICD) is the only powerful treatment modality for Brugada syndrome in patients presenting with ventricular fibrillation (VF). For those whose first presentation is an electrical storm, pharmacologic therapy is typically used to control VF followed by ICD implantation. We report an alternative approach whereby, before ICD implantation, emergency catheter ablation of the VF-triggering premature ventricular contraction (PVC) resulted in long-term VF-free survival. The results suggest that, because VF triggers appear in a narrow time window, ablation of the culprit PVCs that initiate VF before the index PVCs subside is a reasonable alternative approach.