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Detecting high-risk patients for early rehospitalization is crucial in heart failure patient care. An association of albuminuria with cardiovascular events is well known. However, its predictive impact on rehospitalization for acute decompensated heart failure (ADHF) remains unknown. In this study, 190 consecutive patients admitted due to ADHF between 2017 and April 2019 who underwent urinalysis were enrolled. Among them, 140 patients from whom urine albumin-to-creatinine ratio (UACR) was measured with spot urine samples on admission were further analyzed. The association between UACR and rehospitalization due to HF during 1 year after discharge was evaluated. The mean age of 140 participants was 77.6 years and 55% were men. Only 18% (n = 25) of patients presented with normoalbuminuria (UACR 30 mg/g∙creatinine), whereas 59% (n = 83) and 23% (n = 32) showed microalbuminuria (UACR 30-300 mg/g·creatinine) and macroalbuminuria (UACR 300 mg/g·creatinine), respectively. The level of UACR on admission was correlated with the risk of subsequent rehospitalization due to HF (p = 0.017). The receiver operating characteristic analysis indicated that the best cut-off values for the UACR and B-type natriuretic peptide (BNP) levels to predict ADHF rehospitalization were 50 mg/g·creatinine and 824 pg/ml, respectively. When the patients were divided into four groups using both cut-off values, the individual predictive impacts of UACR and BNP on rehospitalization were comparable. Patients with both elevated UACR and BNP levels had a higher rate of HF rehospitalization than those with elevated BNP levels alone (p 0.05). The combination of both values enabled more accurate prediction of HF rehospitalization than BNP levels alone. In conclusion, UACR could be a new useful biomarker to predict HF rehospitalization in patients with ADHF, especially in combination with the levels of BNP, and should be further evaluated in a prospective study.

Background: Anticoagulation for patients with atrial fibrillation (AF) complicated by left atrial thrombi (LAT) is a frequent cause of bleeding complications, but risk factors remain unknown. Methods and Results: Of 3,139 AF patients who underwent transesophageal echocardiography, 82 with LAT under anticoagulation were included in this study. Patients treated with combination antiplatelet and anticoagulant therapy (n=31) were compared with those receiving anticoagulant monotherapy (n=51) to investigate the effects of antiplatelet agents during anticoagulation on bleeding complications. Over a mean (±SD) follow-up of 878±486 days, bleeding events occurred more frequently in the combination therapy than monotherapy group (58% vs. 20%; P

Aim The European Resuscitation Council guidelines recommend a slow rate of rewarming of 0.25 °C/h–0.5 °C/h for out-of-hospital cardiac arrest (OHCA) patients receiving therapeutic hypothermia (TH). Conversely, a very slow rewarming of 1 °C/day is generally applied in Japan. The rewarming duration ranged from less than 24 h up to more than 50 h. No randomized control trials have examined the optimal rewarming speed for TH in OHCA patients. Therefore, we examined the association between the rewarming duration and neurological outcomes in OHCA patients who received TH. Methods This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry, a multicenter prospective cohort study. Patients suffering from OHCA who received TH (target temperature, 34 °C) after the return of spontaneous circulation from 2005 to 2011 in 14 hospitals throughout Japan were enrolled. The rewarming duration was defined as the time from the beginning of rewarming at a target temperature of 34 °C until reaching 36 °C. The primary outcome was an unfavorable neurological outcome at hospital discharge, i.e., a cerebral performance category of 3–5. Results The J-PULSE-HYPO study enrolled 452 OHCA patients. Of these, 328 were analyzed; 79.9% survived to hospital discharge, of which 56.4% had a favorable neurological outcome. Multivariable logistic regression analysis revealed that the rewarming duration was independently associated with unfavorable neurological outcomes [odds ratio (per 5 h), 0.89; 95% confidence interval, 0.79–0.99; p = 0.032]. Conclusion A longer rewarming duration was significantly associated with and was an independent predictor of favorable neurological outcomes in OHCA patients who received TH.

Background: The 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that comatose patients with return of spontaneous circulation after cardiac arrest have targeted temperature management (TTM). However, the duration of TTM remains to be elucidated. Methods and Results: We conducted a cluster randomized trial in 10 hospitals to compare 12–24 vs. 36 h of cooling in patients with cardiac arrest who received TTM. The primary outcome was the incidence, within 1 month, of complications including bleeding requiring transfusion, infection, arrhythmias, decreasing blood pressure, shivering, convulsions, and major adverse cardiovascular events. Secondary outcomes were mortality and favorable neurological outcome (Cerebral Performance Categories 1–2) at 3 months. Random-effects models with clustered effects were used to calculate risk ratios (RR). Data of 185 patients were analyzed (12- to 24-h group, n=100 in 5 hospitals; 36-h group, n=85 in 5 hospitals). The incidence of complications within 1 month did not differ between the 2 groups (40% vs. 34%; RR 1.04, 95% confidence interval [CI] 0.67–1.61, P=0.860). Favorable neurological outcomes at 3 months were comparable between the 2 groups (64% vs. 62%; RR 0.91, 95% CI 0.72–1.14, P=0.387). Conclusions: TTM at 34℃ for 12–24 h did not significantly reduce the incidence of complications. This study did not show superiority of TTM at 34℃ for 12–24 h for neurologic outcomes.

Right ventricular apical (RVA) pacing often causes left ventricular (LV) mechanical asynchrony, which is enhanced by impaired cardiac contraction and intrinsic conduction abnormality. However, data on patients with normal cardiac function and under RV non-apical (non-RVA) pacing are limited.We retrospectively investigated 97 consecutive patients with normal ejection fraction who received pacemaker implantation for atrioventricular block with the ventricular lead placed in a non-RVA position. We defined mechanical asynchrony as discoordinate contraction between opposing regions of the LV wall evaluated by echocardiography. Asynchrony was detected in 9 (9%) patients at baseline and in 38 (39%) under non-RVA pacing (P < 0.001). Asynchrony at baseline was significantly associated with complete left bundle branch block (CLBBB) [odds ratio (OR) = 20.8, P < 0.001]. Asynchrony under non-RVA pacing was significantly associated with left anterior fascicular block (LAFB) (OR = 7.14, P < 0.001) and CLBBB (OR = 13.3, P = 0.002) at baseline. New occurrence of asynchrony was significantly associated with LAFB at baseline (OR = 5.88, P = 0.001). During a median follow-up period of 4.8 years, the incidence of device-detected atrial fibrillation (AF) was more frequent in patients who developed asynchrony than in those who did not (53.3% versus 27.5%, hazard ratio = 2.17, 95% confidence interval = 1.02-4.61, P = 0.03).In patients with normal cardiac function, LAFB at baseline was significantly associated with new occurrence of mechanical asynchrony under non-RVA pacing. Abnormal contraction had a significant influence on the incidence of device-detected AF.

Background Atrial fibrillation (AF) and ventricular arrhythmias (VAs) are associated with increased morbidity and mortality. However, data are lacking concerning the association of AF and VAs. This study aimed to clarify the association between AF and VAs and to investigate the effect of amiodarone on the incidence of VAs in patients with implantable cardioverter defibrillators (ICDs). Methods and results We enrolled 612 patients who had ICDs or who underwent cardiac resynchronization therapy with a defibrillator (CRT-D) and classified them into two groups (sinus rhythm [SR] group, n = 427; AF group, n = 185) according to their basal rhythm at enrollment. Patients with paroxysmal AF were grouped into the AF group. The incidence of VAs, i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF), was significantly lower in the AF group than in the SR group (0.54 vs 0.95 episodes/person/year, P = 0.032). Furthermore, amiodarone use was significantly higher in the AF group than in the SR group (P = 0.003). Non-use of amiodarone was associated with a significant increase in the occurrence of VT/VF in the two groups. This beneficial suppressive effect of amiodarone on the incidence of VT/VF was present in the AF group regardless of left ventricular ejection fraction (LVEF). However, this effect of amiodarone was present only in patients with LVEF ≥ 40% in the SR group. Conclusions Amiodarone was negatively associated with VT/VF occurrence and was frequently used in ICD/CRT-D patients with AF. VT/VF was controlled by amiodarone in all cases in the AF group but only in patients with an LVEF ≥ 40% in the SR group.

Bradycardia during therapeutic hypothermia has been reported to be a predictor of favorable neurologic outcomes in out-of-hospital cardiac arrests. However, bradycardia occurrence rate may be influenced by the target body temperature. During therapeutic hypothermia, as part of the normal physiologic response, heart rate decreases in the cooling phase and increases during the rewarming phase. We hypothesized that increased heart rate during the rewarming phase is another predictor of favorable neurologic outcomes. To address this hypothesis, the study aimed to examine the association between heart rate response during the rewarming phase and neurologic outcomes in patients having return of spontaneous circulation after out-of-hospital cardiac arrest.A secondary analysis of the Japanese Population-based Utstein style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia registry, which was a multicenter prospective cohort study.Fourteen hospitals throughout Japan.Patients suffering from out-of-hospital cardiac arrest who received therapeutic hypothermia after the return of spontaneous circulation from 2005 to 2011.None.This study enrolled 452 out-of-hospital cardiac arrest patients, of which 354 were analyzed, and 80.2% survived to hospital discharge, of which 57.3% had a good neurologic outcome. Heart rate response was calculated using heart rate data recorded during therapeutic hypothermia in the abovementioned registry. Heart rate response in the rewarming phase (heart rate response-rewarming) was calculated as follows: (heart rate [post rewarming]-heart rate [pre rewarming])/heart rate (pre rewarming) × 100. The primary outcome was an unfavorable neurologic outcome at hospital discharge, that is, a Cerebral Performance Category of 3-5. Multivariable logistic regression analysis was performed to determine the association between heart rate response-rewarming and unfavorable neurologic outcomes. Multivariable logistic regression analysis showed that heart rate response-rewarming was independently associated with unfavorable outcomes (odds ratio [per 10% change], 0.86; 95% CI, 0.78-0.96; p = 0.004).Increased heart rate in the approximately 48-hour rewarming phase during therapeutic hypothermia was significantly associated with and was an independent predictor of favorable neurologic outcomes during out-of-hospital cardiac arrest.

Background First-generation drug-eluting stents (DES) have reduced short-term stent failure as compared to bare-metal stents due to the inhibition of neointima hyperplasia, but instead increased the risk of very-late stent failure. Although better outcomes have been reported for second-generation DES than for first-generation DES, the difference in the angioscopic findings at 1-year follow-up has not been adequately elucidated among second-generation DES. Methods Consecutive 161 patients who received angioscopic examination at 1 year after implantation of second-generation DES, i.e. Nobori biolimus-eluting stents (Terumo, Tokyo, Japan) (N-BES, n = 25), Xience everolimus-eluting stents (Abbot Vascular, Santa Clara, CA, USA; X-EES, n = 95), or Resolute zotarolimus-eluting stents (Resolute Integrity; Medtronic, Minneapolis, MN, USA; R-ZES, n = 41), in de novo native coronary lesions were analyzed. Results Maximum neointima coverage grade (N-BES, 0.9 ± 0.3; X-EES, 1.2 ± 0.4; R-ZES, 1.5 ± 0.5; p

The aim of this study was to evaluate the association of functional mitral regurgitation (FMR), preserved or reduced ejection fraction (EF), and ischemic or nonischemic origin with outcomes in patients discharged alive after hospitalization for acute decompensated heart failure (HF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 3,357 patients were evaluated to assess the association of FMR, preserved or reduced EF, and ischemic or nonischemic origin with the primary end point (all-cause death and readmission for HF after discharge). At the time of discharge, FMR was assessed semiquantitatively (classified as none, mild, or moderate to severe) by color Doppler analysis of the regurgitant jet area. According to multivariable analysis, in the ischemic group, either mild or moderate to severe FMR in patients with a preserved EF had a significantly higher risk of the primary end point than patients without FMR (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.12 to 2.29; p = 0.010 and HR 1.98; 95% CI 1.30 to 3.01; p = 0.001, respectively). In patients with reduced EF with an ischemic origin, only moderate to severe FMR was associated with a significantly higher risk of the primary end point (HR 1.67; 95% CI 1.11 to 2.50; p = 0.014). In the nonischemic group, there was no significant association between FMR and the primary end point in patients with either a preserved or reduced EF. In conclusion, among patients with acute decompensated HF with a preserved or reduced EF, the association of FMR with adverse outcomes may differ between patients who had an ischemic or nonischemic origin of HF.

The aim of this study was to examine the impact of the serum eicosapentaenoic acid (EPA) to arachidonic acid (AA) ratio on recurrence after catheter ablation (CA) for atrial fibrillation (AF).A total of 192 patients who underwent first-time radiofrequency CA for AF were enrolled in this study. They were divided into two groups based on the median serum EPA/AA ratio before CA: a LOW group (< 0.30; n = 96) and a HIGH group (≥ 0.30; n = 96). Patients in the LOW group were younger and had smaller left atrial diameter (LAD) than those in the HIGH group. Although pulmonary vein triggers initiating AF were more frequently observed in the LOW group than the HIGH group (63% versus 46%, respectively; P = 0.021), no significant between-group difference was observed regarding the incidence of AF recurrence since the last procedure (17% versus 17%, P = 0.78; median follow-up, 37 months). Multivariate Cox regression analysis after adjustment for age and LAD revealed that EPA/AA of < 0.30 was not a significant predictor of AF recurrence (hazard ratio, 1.12; 95% confidence interval 0.53-2.37; P = 0.76). However, in the non-paroxysmal AF subgroup (n = 65), the incidence of AF recurrence was significantly higher in the LOW group than in the HIGH group (25.7% versus 6.7%, respectively; P = 0.031).In conclusion, a lower preprocedural EPA/AA ratio, which was associated with younger age and small left atrium, was not a predictor for the risk of AF recurrence after CA for AF. The potential impact of the ratio on recurrence in non-paroxysmal AF subgroups should be examined with larger samples.

BACKGROUND Drug-eluting stents (DES) have reduced late loss and target lesion revascularization through the inhibition of neointimal hyperplasia, but instead increased the risk of very late stent failure due to incomplete neointimal coverage and neoatherosclerosis. Although newer DES are more effective and safer than the first-generation DES, the difference in the condition of the stented lesions between Resolute zotarolimus-eluting stents (R-ZES) and Endeavor zotarolimus-eluting stents (E-ZES) on angioscopy has not been reported. METHODS AND RESULTS Consecutive patients who received R-ZES (n=46) or E-ZES (n=46) for de novo lesion of native coronary artery and had 1-year follow-up angioscopy were examined. Yellow color (grade 0-3), neointimal coverage (grade 0-2), heterogeneity score (maximum-minimum neointimal coverage grade) and thrombus (presence or absence) at stented lesion were evaluated. The maximum yellow color grade (1.2±0.9 vs. 0.7±1.0, P=0.005) was higher in R-ZES than in E-ZES. The maximum (1.9±0.3 vs. 1.5±0.5, P

Background The monitoring of tissue hypoperfusion and the subsequent neurohumoral activation (ie, arterial underfilling) during decongestion is important for the management of acute decompensated heart failure (ADHF). The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity. This study tested the hypothesis that TTKG can be a surrogate of arterial underfilling in patients with ADHF. Methods and results We measured TTKG at discharge in 100 ADHF patients. The primary outcome measure was the occurrence of tissue hypoperfusion events (defined according to the "Cold Modified 2014" definition criteria) within 1 month after discharge. The secondary outcome measure was the occurrence of cardiac death or ADHF readmission within 3 months after discharge. On receiver operating characteristic curve analysis, TTKG predicted tissue hypoperfusion events with high accuracy (C-statistic, 0.889) for a cut-off of 6.0. Multivariate Cox regression analyses demonstrated independent relationships between TTKG and both the primary and secondary outcomes. Conclusions TTKG has utility as a surrogate of arterial underfilling, and spot TTKG at discharge may be a prognostic marker in ADHF patients. (Circ J 2016; 80: 1965-1970).

Background: Brain natriuretic peptide (BNP) is routinely measured for evaluating the severity of acute decompensated heart failure (ADHF). However, there are no other biomarkers for stratification of ADHF patients in clinical settings. Cardiac myosin I (CM-I) is one of a superfamily of motor proteins, which is mainly distributed in myocardium. Several papers reported that serum CM-I levels increased in patients with acute coronary syndrome (ACS). However, the role of CM-I in ADHF patients is not yet elucidated. Purpose: The aim of this study was to clarify the utility of CM-I in ADHF patients. Methods: We assessed 114 ADHF patients who visited our institution between December 2017 and May 2018 in a retrospective study. All patients were diagnosed ADHF using Framingham criteria. Eight ACS patients and 22 patients lacking in data of serum CM-I levels were excluded. Finally, we analyzed 84 patients. We calculated the difference in serum BNP levels between on admission and at discharge (delta BNP) as a prognostic surrogate marker. Results: Average age was 77.5 years old and 44 patients were male. Numbers of patients with NYHA III and IV were 30 and 36, respectively. Mean serum levels of BNP and Troponin T (TrT) on admission were 934.0 pg/ml and 0.092 ng/ml, respectively. Average left ventricular ejection fraction (LVEF) by echocardiography was 46.1%. Serum CM-I levels on admission and at discharge were 12.8 mg/ml and 7.30 mg/ml, respectively. Serum CM-I levels had a significant correlation with TrT levels (R=0.46, p Conclusion: We found CM-I was associated with the difference in BNP between on admission and at discharge in ADHF patients. CM-I may be a new potential prognostic biomarker in ADHF patients.

Right ventricular apical (RVA) pacing often causes left ventricular (LV) mechanical asynchrony, which is enhanced by impaired cardiac contraction and intrinsic conduction abnormality. However, data on patients with normal cardiac function and under RV non-apical (non-RVA) pacing are limited.We retrospectively investigated 97 consecutive patients with normal ejection fraction who received pacemaker implantation for atrioventricular block with the ventricular lead placed in a non-RVA position. We defined mechanical asynchrony as discoordinate contraction between opposing regions of the LV wall evaluated by echocardiography. Asynchrony was detected in 9 (9%) patients at baseline and in 38 (39%) under non-RVA pacing (P0.001). Asynchrony at baseline was significantly associated with complete left bundle branch block (CLBBB) [odds ratio (OR) = 20.8, P0.001]. Asynchrony under non-RVA pacing was significantly associated with left anterior fascicular block (LAFB) (OR = 7.14, P0.001) and CLBBB (OR = 13.3, P = 0.002) at baseline. New occurrence of asynchrony was significantly associated with LAFB at baseline (OR = 5.88, P = 0.001). During a median follow-up period of 4.8 years, the incidence of device-detected atrial fibrillation (AF) was more frequent in patients who developed asynchrony than in those who did not (53.3% versus 27.5%, hazard ratio = 2.17, 95% confidence interval = 1.02-4.61, P = 0.03).In patients with normal cardiac function, LAFB at baseline was significantly associated with new occurrence of mechanical asynchrony under non-RVA pacing. Abnormal contraction had a significant influence on the incidence of device-detected AF.

Background Identifying who among current Japanese patients with prior myocardial infarction (MI) would benefit from an implantable cardioverter-defibrillator (ICD) is imperative. Accordingly, this study seeks to determine whether single-photon emission computed tomography (SPECT) can help identify such patients. Methods and Results: This retrospective study enrolled 60 consecutive patients with prior MI who underwent stress thallium-201 SPECT and ICD implantation from February 2000 to October 2014. Occurrence of arrhythmic death and/or or appropriate ICD therapy, defined as shock or antitachycardia pacing for ventricular fibrillation or tachycardia, was identified until November 2016. During the median follow-up interval of 6.6 years, 18 (30%) patients experienced arrhythmic death and/or appropriate ICD therapy. Multivariate Cox proportional hazard regression analysis revealed that the summed stress score (SSS) [hazard ratio (HR)=1.14; P=0.005] and left ventricular ejection fraction (LVEF) at rest (HR=0.92; P=0.038) were significantly associated with the occurrence of arrhythmic events. Patients with SSS ≥21 and LVEF ≤30%, which were determined to be the best cutoff points, had significantly higher incidence of the arrhythmic events than the other patients (64% vs. 11%; HR=7.18; log-rank P=0.001). Conclusions SSS using stress thallium-201 SPECT in combination with LVEF can help determine the need for ICD therapy among current Japanese patients with prior MI.

Background Although extensive substrate modification in addition to pulmonary vein isolation (PVI) has been recommended in catheter ablation for persistent atrial fibrillation (AF), recent randomized controlled trials have not demonstrated efficacy of such additional ablations. Methods and study design The Osaka Cardiovascular Conference will conduct a multicenter, randomized, open-label trial aiming to examine whether PVI alone is non-inferior to PVI plus additional ablation such as linear ablation and/or complex fractionated atrial electrogram ablation in patients with persistent AF. The primary outcome is recurrence of AF documented by scheduled or symptom-driven electrocardiogram tests during a 1-year follow-up period after the index ablation. The key secondary endpoints include all-cause death, occurrence of symptomatic stroke, complications related to the procedure, and quality of life assessment using the 36-item Short-Form Health Survey. The clinical impact of the presence or absence of AF trigger foci, and their origins in cases with them, on the results of catheter ablation will also be investigated as an exploratory endpoint. A total of 512 patients will be enrolled and followed up to 1 year. Conclusions The EARNEST-PVI trial is a randomized controlled trial designed to assess whether PVI alone is non-inferior to extended substrate ablation for patients with persistent AF undergoing a first catheter ablation.

Background Newer implantable cardioverter defibrillators can monitor intracardiac ECGs , but their ability to detect ischemia is unclear. This study investigated the usefulness of implantable cardioverter defibrillators with an ST‐monitoring function in coronary artery disease patients. Methods and Results We conducted a prospective study of implantable cardioverter defibrillator patients with the ST‐monitoring function. One hundred seventy‐three patients who received implantable cardioverter defibrillators for primary or secondary prevention of sudden cardiac death. All patients underwent medical examinations at least every 6 months, with standard 12‐lead ECGs and device checks that included analysis of the ST‐monitoring function. Myocardial perfusion imaging or coronary angiography was performed during the follow‐up. The mean follow‐up duration was 23.3±7.7 months. Significant ST changes occurred in 15 patients (8.7%), of whom 14 were asymptomatic. The incidence of angina pectoris was significantly higher in the ST change (+) group than that in the ST change (−) group (28.6% versus 7.2%, P =0.03). In the patients who underwent myocardial perfusion imaging, the sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to detect ischemia were 75.0%, 72.5%, and 93.5%, respectively. The sensitivity, specificity, and negative predictive value of the ST‐monitoring feature to predict residual stenosis evaluated using coronary angiography were 76.9%, 83.5%, and 97.5%, respectively. The percentage of patients with a septal right ventricular lead was significantly lower in the ST change (+) group than in the ST change (−) group (13.5% versus 33.5%, P =0.01). Conclusions If intracardiac ECGs ST changes are detected, it is necessary to use additional modalities even in asymptomatic patients. Clinical Trial Registration URL: upload.umin.ac.jp . Unique identifier: UMIN000011824.

Objectives This study examined whether coronary angioscopy-verified in-stent yellow plaque at 1 year after drug-eluting stent (DES) implantation is associated with future event of very late stent failure (VLSF). Background Atherosclerosis detected as yellow plaque by angioscopy has been associated with future events of acute coronary syndrome. Development of in-stent neoatherosclerosis is a probable mechanism of VLSF. Methods This study included 360 consecutive patients who received successful angioscopic examination at 1 year after implantation of a DES. They were clinically followed up for VLSF defined as cardiac death, acute myocardial infarction or unstable angina, or need for revascularization associated with the stent site. Results The follow-up interval was 1,558 ± 890 days (4.3 ± 2.4 years). The incidence of VLSF was significantly higher in the patients with yellow plaque than in those without (8.1% vs. 1.6%; log rank p = 0.02). Multivariable analysis revealed the presence of yellow plaque (hazard ratio [HR]: 5.38; p = 0.02) and absence of statin therapy (HR: 3.25; p = 0.02) as risks of VLSF. Conclusions In-stent atherosclerosis evaluated by yellow plaque at 1 year after the implantation of DES and the absence of statin therapy were risks of VLSF. The underlying mechanism of VLSF appeared to be the progression of atherosclerosis as demonstrated by the yellow plaque.

Drug-eluting stents (DESs) in comparison with bare metal stents (BMSs) have reduced early target lesion revascularization (TLR) through exerting an inhibitory effect on smooth muscle cell hyperplasia but have also increased the risk of stent thrombosis and TLR after 1 year, in other words, very-late stent failure (VLSF). Neoatherosclerosis or atherosclerosis progression is thought to be the major mechanism and is regarded as a ‘final common pathway of VLSF.’ Atherosclerosis can be detected by various intracoronary imaging modalities; e.g., angioscopy detects it as yellow plaque that has been regarded as vulnerable plaque and is associated with future event of acute coronary syndrome. Here, the findings of neoatherosclerosis using intracoronary imaging are reviewed and their relation with the long-term clinical outcome is discussed.

BACKGROUND Bacterial cultures of cardiovascular implantable electronic devices removed from patients without clinical infection are often positive, and the cultured bacteria are different from those at the time of clinical infection. This discrepancy has not been adequately explained. We hypothesized that the cause is bacterial contamination at operation and compared the results of bacterial cultures between patients with de novo pacemaker implantation and those with pacemaker replacement. METHODS AND RESULTS We prospectively enrolled consecutive 100 patients who underwent cardiac pacemaker implantation (49 de novo implantations, 51 replacements). We took swab cultures from inside the generator pocket (1) immediately after the creation of new pocket or removal of old generator, (2) after connection of leads to new generator, and (3) after pocket lavage. Swab cultures were positive in 272 (45%) of 600 samples. The majority of the cultured bacteria were Propionibacterium species. No statistical difference was detected between de novo implantations and replacements in the positive ratio of swab cultures. The positive ratio was not correlated with the number of previous device replacements. CONCLUSIONS The positive ratio of swab cultures was not different between new implantations and replacements, suggesting that a positive culture merely indicates contamination of bacteria during operation rather than colonization.

Background Although central venous pressure (CVP) is a surrogate measure of preload in patients with acute decompensated heart failure (ADHF), it is a multifactorial index influenced not only by fluid volume status, but also by cardiac pump function and other factors. We aimed to elucidate the individual pathophysiological factors of CVP elevation in patients with ADHF by assessing the relationship between CVP and extracellular fluid volume status (EVS). Methods and Results We quantified EVS in 100 patients with ADHF with the use of bioelectrical impedance analysis. CVP was also measured at the same time point. Subjects were categorized into tertiles according to their CVP-EVS ratios, and patient characteristics and clinical outcomes were compared among these tertiles. The upper-tertile group had a higher incidence of impaired right ventricular pump function, whereas the lower-tertile group had higher incidences of severe inflammation, hypoalbuminemia, and renal dysfunction. Patients in both the upper and lower tertiles had a significantly higher cardiac event rate than those in the middle tertile. Conclusions The combined assessment of CVP and EVS provides insight into both the total volume status and distribution of body fluid in ADHF patients, and it may have applications in guiding decongestive therapy and improving prognostic predictions.

Although we have occasionally experienced silent thrombi in the left atrium (LA), defined as thrombi free from embolic events, by screening transesophageal echocardiography (TEE) for atrial fibrillation (AF), few data are available on predictors and outcomes of silent LA thrombi in patients with AF. We retrospectively reviewed clinical records and identified 83 patients (2.6%) with silent LA thrombi, out of 4,214 TEE procedures in 3,139 patients with AF at 6 hospitals from January 2010 to December 2012. The median [interquartile range] CHA2DS2-VASc score was 3 [2, 5]. Most patients (n = 71, 86%) were taking oral anticoagulants before the TEE, and 59 patients (71%) had heart failure (HF). During follow-up periods of 905 [620, 1301] days, ischemic stroke and systemic embolism, and hemorrhagic stroke occurred only in 3 (3.6%) and 2 patients (2.4%), respectively. All-cause death developed in 14 patients (17%), and cardiac death was the primary cause of death (n = 9, 11%). Multivariate Cox regression analysis showed the composite end point of death, stroke, systemic embolism, and major bleeding was significantly associated with age (hazard ratio; 1.06, 95% confidence interval; 1.01 to 1.11, p = 0.019) and HF (3.18, 1.27 to 7.99, p = 0.014). In conclusion, the incidence of ischemic stroke after detecting silent LA thrombi was relatively low in patients with AF under oral anticoagulation. Advanced age and HF were predictors for worse outcomes in AF patients with silent LA thrombi.

Yellow plaques detected by coronary angioscopy have been regarded as vulnerable plaques and associated with distal embolization or slow/no-flow phenomenon during coronary intervention. This is the first report that compared the findings of angioscopy and near-infrared spectroscopy (NIRS) in a patient who suffered no-flow phenomenon during coronary intervention.A 41-year-old male patient with silent myocardial ischemia received coronary intervention. Coronary angiogram revealed diffuse stenosis in the distal right coronary artery. Target lesion was examined by NIRS and angioscopy. NIRS can detect lipid core plaque, which is presented as an yellow area in contrast to the normal red area. Target segment was filled with lipid core plaques. On the other hand, angioscopy revealed a ruptured yellow plaque with a thrombus in the target segment. The distribution of yellow plaques detected by angioscopy appeared well corresponded to the yellow areas detected by NIRS. After the insertion of filter-type distal protection device, balloon pre-dilatation and stent implantation were performed. Then, no-flow phenomenon occurred. Coronary flow was finally recovered in the protected vessel but was still disturbed in the non-protected vessel. The filter was filled with much plaque debris.The correlation between the yellow area detected by NIRS and the yellow plaques detected by angioscopy appeared very well.

Background:Theslow-flow or no re-flow phenomenon has been associated with distal embolization, especially of plaque debris, and with unfavorable clinical outcomes. Therefore, we examined the association between the coronary computed tomography angiography (CCTA) findings of the target lesion and distal embolization during percutaneous coronary intervention (PCI).Methods and Results:Consecutive patients (n=55: 18 unstable angina, 19 stable effort angina, 18 silent ischemia) who underwent PCI with a filter-type distal protection device after evaluation of the target lesion by CCTA were analyzed. CCTA examined low-attenuation plaque (LAP), positive remodeling (PR), and ring-like enhancement of the target lesion. Distal embolization of thrombus and plaque debris was evaluated by pathological examination of material collected in the filter.Any distal embolization and distal embolization of plaque debris were respectively detected in 75% and 0% of patients with LAP or PR alone, in 95% and 17% of patients with both LAP and PR, and in 100% and 27% of patients with all of LAP, PR and ring-like enhancement. The sensitivity and specificity to predict plaque debris embolization by having both findings of LAP and PR was 100% and 46%, respectively.Conclusions:The CCTA findings of the target lesion were associated with distal embolization and were very sensitive for predicting plaque debris embolization. (Circ J2014;78:2203–2208)

Although plaque rupture is the major cause of acute myocardial infarction, vasospasm is also known as a potential cause of acute myocardial infarction. However, it is very rare and is sometimes difficult to diagnose correctly. A 30-year-old male patient with suspected unstable angina pectoris who received catheterization in 1999 had normal coronary artery but positive result in the provocation test of vasospasm. Although his angina had been suppressed by medications, he suffered ST-elevation acute myocardial infarction after the discontinuation of medication. The initial angiogram showed total occlusion of the proximal left anterior descending coronary artery. Thrombolysis and nitroglycerin achieved recanalization of the culprit lesion with only mild residual stenosis. Angioscopy revealed normal white luminal wall without any thrombogenic lesion. Therefore, the cause of coronary occlusion was diagnosed as vasospasm. However, since the repeated vasospastic occlusion of the culprit lesion regardless of repeated intra-coronary injection of nitroglycerin was observed, a stent was implanted and vasospasm was successfully prevented. It is not easy to judge from the angiogram that the cause of coronary occlusion in the patients with acute myocardial infarction is vasospasm. It is important to think routinely about the possibility of vasospasm as a cause of acute myocardial infarction.

Neoatherosclerosis or atherosclerosis progression is one of the mechanisms of long-term stent failure. Yellow plaque detected by angioscopy has been associated with advanced atherosclerosis and the future risk of a coronary event. We compared the yellow colour of the stented segment between zotarolimus-eluting stents (ZES) and everolimus-eluting stents (EES) at 1 year after implantation.Cross-sectional study.Consecutive patients underwent angioscopic examination 1 year after the implantation of ZES (n=45) or EES (n=45) at a de novo native coronary lesion.The maximum yellow colour grade (grade 0-3) of the stented segment, maximum and minimum neointima coverage grade (grade 0-2) and the presence of thrombus were examined. The neointima heterogeneity index was calculated as maximum - minimum coverage grade.Maximum yellow colour grade was higher in EES than in ZES (1.3±0.9 vs 0.4±0.8, p0.001) and maximum (2.0±0.2 vs 1.2±0.5, p0.001) and minimum (1.5±0.6 vs 0.7±0.5, p0.001) coverage grade was higher in ZES than in EES. The neointima heterogeneity index was not different between ZES and EES (0.4±0.5 vs 0.5±0.6, p=0.42). The incidence of thrombus was very low and was not different between ZES and EES (2% vs 4%, p=0.55).Although both ZES and EES had good healing with homogeneous neointima coverage and a low incidence of thrombus, EES had more advanced atherosclerosis as shown by the presence of higher grade yellow plaque than ZES at 1 year after implantation.

AIMS Slow flow and no flow phenomena have been associated with distal embolisation, especially of plaque debris, and with unfavourable clinical outcomes. However, patients at high risk of distal embolisation for whom distal protection might be beneficial have not been adequately identified. We examined the frequency of distal embolisation and its predicting factors, including both ACS and non-ACS patients. METHODS AND RESULTS Consecutive patients (n=98) with or without ACS who had received PCI with a filter-type distal protection device and successful angioscopic and VH-IVUS examination were prospectively enrolled. The presence of yellow plaque and plaque rupture was evaluated by angioscopy. Tissue classification and plaque burden was evaluated by VH-IVUS. Distal embolisation was evaluated by pathological examination of material collected in the filter. Distal embolisation of plaque debris was more frequently detected in patients with ACS (48% vs. 25%, p=0.02), in those with ruptured plaque (86% vs. 13%, p 75%) plaque burden (50% vs. 23%, p=0.006), and in those with grade 2/3 yellow plaque (52% vs. 7%, p

Background: Plaque disruption and its healing is thought to be the major mechanism of atherosclerosis, but the contribution of silent plaque disruption to luminal stenosis progression has not been fully clarified. The aim of this study was therefore to examine the change in luminal stenosis at the site of silent plaque disruption. Methods and Results: Consecutive patients (n=36) who received coronary angiography and angioscopy that identified silent plaque disruption (baseline) and had repeated coronary angiography later (follow-up) were included for analysis. Silent plaque disruption was defined as plaque with thrombus detected in non-culprit segments. Diameter stenosis of the site was angiographically measured at baseline and at follow-up, and their difference was defined as stenosis change. Statin was used in 89% of study patients, and serum low-density lipoprotein cholesterol level was 91±21mg/dl. The diameter stenosis decreased significantly from baseline to follow-up at 12±4 months (32±14% vs. 27±14%, P

Clinical outcome is generally poor when stents are implanted at right coronary artery ostial lesion (RCAos). We compared the clinical outcome between the first-generation drug-eluting stent (first DES) and second-generation drug-eluting stent (second DES) used for RCAos. Consecutive 88 patients who underwent percutaneous coronary interventions of de novo RCAos using the first DES (33 patients) or second DES (55 patients) were analyzed. The incidence of major adverse cardiac events (MACE) defined as the composite of cardiac death, myocardial infarction attributed to right coronary artery, and target lesion revascularization within 2.5 years was compared. The incidence of MACE was significantly lower in second DES (11% vs 36%, p = 0.010) than that in the first DES. Multivariate analysis revealed use of second DES (odds ratio 0.24, 95% CI 0.11 to 0.93, p = 0.008) alone was significantly associated with MACE. In conclusion, second DES revealed better clinical outcome than the first DES when used in de novo RCAos.

Background Dissociated pulmonary vein activity (DPVA), defined as isolated intrinsic ectopic beats observed after successful pulmonary vein (PV) isolation, indicates the presence of remnant foci of trigger ectopy but has yet to be extensively studied. We investigated the correlation between DPVA and the PV triggers of atrial fibrillation (AF). Method and results Consecutive 110 patients undergoing AF ablation were enrolled. We defined trigger ectopy as documented ectopic foci observed to spontaneously initiate AF. Trigger ectopy was detected in 62 (56%) patients. DPVA in at least one PV was detected in 95 (86%) patients. Of the 440 isolated PVs, we recognized trigger ectopy in 73 (16%) PVs (culprit PVs) and DPVA in 184 (42%) PVs. DPVA was more frequently observed in culprit PVs than in non-culprit PVs [59% vs. 39%; odds ratio (OR) = 2.3; p = 0.001]. The concordance ratio of culprit PV was 67% (8/12) in PV with fibrillatory DPVA, 20% (35/172) in PV with non-fibrillatory DPVA, and 12% (30/256) in PV without DPVA. Fibrillatory DPVA was more frequently observed in culprit PVs than non-fibrillatory DPVA (OR = 7.8; p = 0.001). Non-PV foci were observed in 10 (11%) of the 95 patients with DPVA and 5 (33%) of the 15 patients without DPVA (OR = 4.3; p = 0.02). No significant difference in the frequency of AF recurrence was observed between them. Conclusions Fibrillatory DPVA was found to be strongly associated with trigger ectopy of AF. Non-fibrillatory DPVA might merely indicate the existence of bystander ectopic foci located inside PVs. Non-PV ectopic foci were frequently observed in patients without DPVA.

SummaryAlthough very late stent thrombosis after drug-eluting stent implantation is a critical event, its cause has not been clarified. This is the first report of a case with very late stent thrombosis after drug-eluting stent implantation for which prior angioscopic image of the culprit lesion is available.A 54-year-old Japanese male patient with stable angina who received implantation of sirolimus-eluting stent at the culprit lesion and 1-year follow-up angiographic and angioscopic examinations came back with chest pain at rest at 2.5 years after the stent implantation. Very late stent thrombosis was diagnosed by emergent angiographic and angioscopic examinations and was treated by zotarolimus-eluting stent. One-year angiographic and angioscopic follow-up examinations after zotarolimus-eluting stent were performed. Angioscopy revealed uncovered stent strut, yellow plaques, and thrombus at 1-year follow-up after sirolimus-eluting stent implantation, and it confirmed the thrombotic occlusion inside the sirolimus-eluting stent at the time of emergent catheterization.This is a case of very late stent thrombosis in the drug-eluting stent where uncovered stent strut, yellow plaques, and thrombus had been detected by angioscopy 1.5 years before the onset. Those thrombogenic sources might be the cause of stent thrombosis.

Background: A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) has been associated with cardiovascular events. Higher-grade yellow color coronary plaques are associated with higher plaque vulnerability and higher thrombogenic potential. Therefore, the association between EPA/AA ratio and yellow color grade of coronary plaques was examined. Methods and Results: Consecutive patients (n=54) who underwent percutaneous coronary intervention were enrolled in this study. The serum EPA/AA ratio was examined on admission. All patients underwent an angioscopic examination of the culprit vessel to examine the color grade of yellow plaques (0, white; 1, slight yellow; 2, yellow; and 3, intense yellow) and the presence of thrombus. Excluding 16 patients with acute coronary syndrome (ACS), 38 patients with stable angina were divided into 2 groups according to their EPA/AA ratio: the low EPA/AA group (n=19, EPA/AA ratio

目的：粥状動脈硬化病変（Plaque）は，比較的大きな血管の分枝部など特定部位に好発する特性がある．しかし，左右頸動脈洞（CS）の一方のみにPlaque形成を認めることは，臨床現場にてしばしば遭遇する．我々は，血管径などが一方のみにPlaqueを形成させている要因と推測し，それらの因子がPlaque形成に与える影響について研究した．対象と方法：2009年4月から2010年3月までに医療法人生登会寺元記念西天満クリニックにて頸動脈超音波検査を実施した外来患者の内，左右一方のCSのみにPlaque形成を認めた100例（男性68人，女性32人）を対象とした．頸動脈超音波検査にて，左右両側の総頸動脈（CCA）とCSの接合角，各血管径，血管径比（CS/CCA），平均内膜中膜複合体厚及び流速を求めた．Plaque形成を認めた側をP側，認めない側をN側として，各因子を比較検討した．結果と考察：接合角，CS径とCS/CCAは，P側の方がN側に比較して有意に高値を示した．本研究結果より，血管径や接合角は血管内皮へかかるずり応力に影響し，Plaque形成の重要な因子になると推測された．結論：血管径や接合角がPlaque形成の要因であることが示唆された．

A 78-year-old man was implanted with a cardiac resynchronization therapy defibrillator. One month later, chest X-ray and electrocardiography suggested left ventricular (LV) lead dislodgement. However, the LV lead pacing threshold obtained by a programmer was unchanged because anodal capture had developed, which made it difficult to confirm the LV lead dislodgement. Radiographs obtained in the catheterization laboratory revealed that the tip of the LV lead had dislodged into the right atrium. The LV lead was relocated into another lateral coronary vein. Electrocardiography showed the QRS duration to be shorter than prior to this revision.

Although the concept of vulnerable plaque has become common, it is still impossible to predict effectively the onset of acute coronary syndrome (ACS). Thin-cap fibroatheroma (TCFA) is regarded as vulnerable from pathological studies and various diagnostic tools have tried to detect TCFA clinically but failed to predict ACS. Because there are so many silent plaque ruptures detected, it is supposed that many vulnerable plaques might have ruptured but not caused ACS. Some factor(s) other than the rupture of vulnerable plaque is required for the onset of ACS. "Vulnerable blood" may be one of them. The thrombogenic potential of blood (ie, vulnerable blood) may play an important and determinant role in the onset of ACS, the process of which will be discussed from the angioscopic point of view.

Objectives We sought to examine by angioscopy the neointima formation and thrombogenic potential of the neointima after deployment of a drug-eluting stent (DES). Background Late stent thrombosis after DES implantation, a major safety concern, has been associated with poor strut coverage by neointima. Intracoronary angioscopy provides a method for visual evaluation of stent coverage by neointima and detection of thrombus in the stented coronary segment. Methods Patients undergoing implantation of a sirolimus DES (n = 57) were serially examined by angioscopy immediately after (baseline) and again at 10 months (follow-up) after implantation. The angioscopic color grade of the neointima from white to yellow was assessed in a semiquantitative manner. Stent coverage was classified into not covered (Grade 0), covered by a thin layer (Grade 1), or buried under neointima (Grade 2). The thrombogenic potential of the neointima was evaluated by the prevalence of thrombus on the neointima. Results The maximum yellow color grade of the neointima within DES-implanted lesions increased significantly from baseline to follow-up (1.4 ± 1.1 vs. 1.9 ± 0.6, p = 0.0008). Even among lesions without yellow color at baseline, yellow color was detected in 94% (17 of 18) of lesions at follow-up. The prevalence of thrombus was significantly higher on the yellow than on the white neointimal areas. Thrombus was detected on yellow and/or Grade-0/1 neointima, but never on the white Grade-2 neointima. Conclusions Sirolimus DES promoted formation of atherosclerotic yellow neointima in the stent-implanted lesion at 10-month follow-up. Thrombus was detected more often on the yellow area than on the white area and was never detected where a stent was buried under white neointima. These data suggest that the increased potential risk of late stent thrombosis in DES lesions may be due to the newly formed yellow neotima and cholesterol-laden plaque.

SummaryA 70-year-old woman was performed percutaneous coronary intervention at the stenotic lesion of the 1st diagonal branch. Soon after stenting, cardiac tamponade occurred and emergent cardiac surgery was performed. A large epicardial hematoma was observed in the antero-lateral wall that was compressing the distal diagonal branch. The patient died of multi-organ failure 3 days after surgery. An autopsy of her heart revealed an extensive intramural hematoma in the left ventricular wall. There was no evidence of perforation of the stented lesion. The suspected cause was neither coronary perforation nor coronary rupture of target lesion.

We examined whether the inhibition of apoptosis signal-regulating kinase 1 (ASK1) would attenuate the progression of heart failure in TO-2 hamsters with hereditary dilated cardiomyopathy.Heart failure remains the leading cause of mortality and requires novel therapies targeting the biologically relevant processes within cardiomyocytes that lead to cell death. Apoptosis signal-regulating kinase 1 is a key signaling molecule for cardiomyocyte death.We generated recombinant adeno-associated virus (rAAV) expressing an N-terminal truncated form of the dominant-negative mutant of ASK1 (ASKdeltaN(KR)). TO-2 hamsters were subjected to an in vivo rAAV transcoronary transfer.ASKdeltaN(KR) retained its dominant-negative activity in vitro. The rAAV expressing ASKdeltaN(KR) treatment inhibited ASK1 activation in the hamster hearts and suppressed progression of ventricular remodeling such as chamber dilation, impairment of contractile and relaxation functions, and fibrosis. Inhibition of ASK1 reduced the number of apoptotic cells and selectively attenuated c-Jun NH2-terminal kinase activation. Although the deficiency of delta-sarcoglycan, a genetic defect in the hamster, leads to the degradation of dystrophin, the treatment significantly protected hearts from this degradation, probably by inhibiting calpain activation.Apoptosis signal-regulating kinase 1 is involved in the pathogenesis of heart failure progression, mediated through c-Jun NH2-terminal kinase-mediated apoptosis and calpain-dependent dystrophin cleavage, and may be a therapeutic target to treat patients with heart failure.

BACKGROUND Because the initial (on admission) Glasgow Coma Scale (GCS) examination has not been fully evaluated in comatose survivors of cardiac arrest (CA) who receive therapeutic hypothermia (TH), the aim of the present study was to determine any association between the admission GCS motor score and neurologic outcomes in patients with out-of-hospital CA who receive TH. METHODS AND RESULTS In the J-PULSE-HYPO study registry, patients with bystander-witnessed CA were eligible for inclusion. Patients were divided into 3 groups based on GCS motor score (1, 2-3, and 4-5) to assess various effects on neurologic outcome. Univariate and multivariate analyses were performed to identify independent predictors of good neurologic outcome at 90 days. Of 452 patients, 302 were enrolled. There was a significant difference among the 3 patient groups with regard to neurologic outcome at 90 days in the univariate analysis. Multiple logistic regression analyses showed that the GCS motor score on admission, age >65 years, bystander cardiopulmonary resuscitation, the time from collapse to return of spontaneous circulation, and pupil size

Therapeutic hypothermia (TH) is a standard strategy to reduce brain damage in post-cardiac arrest syndrome (PCAS) patients. However, it is unknown whether the target temperature should be adjusted for PCAS patients in different states. Participants in the J-PULSE-Hypo study database were divided into lower (32.0–33.5 °C; Group L) or moderate (34.0–35.0 °C; Group M) temperature groups. Primary outcome was a favourable neurological outcome (proportion of patients with a Glasgow-Pittsburgh Cerebral Performance Category [CPC] of 1–2 on day 30). We compared between the two groups and in subgroups of patients divided by age and resuscitation interval (interval from collapse to return of spontaneous circulation) by propensity score (PS) analysis. Overall, 467 participants were analysed. The proportions of patients with favourable neurological outcomes were as follows (Group L vs. Group M) (OR; Odds ratio): all patients, 64 % (n = 42) vs. 55 % ((n = 424) (PS; OR 1.381 (0.596–3.197)), P = 0.452) and resuscitation interval ≤ 30 min, 88 % (n = 24) vs. 64 % ((n = 281) (PS; OR 7.438 (1.769–31.272)), P = 0.007). PCAS patients with a resuscitation interval of

To determine the relation between plasma brain natriuretic peptide (BNP) and remodeling in terms of infarct-related artery (IRA) patency, 106 patients with a first anterior wall acute myocardial infarction with a patent IRA at 1 month were studied. The IRA reoccluded at 6 months in 17 patients (reoccluded IRA) and was patent in 89 patients (patent IRA). The 2 groups did not differ with respect to clinical characteristics, hemodynamic variables, and left ventricular function at 1 month, except for left ventricular end-diastolic and systolic volumes, which were significantly greater in the reoccluded IRA group. Plasma BNP concentration in the reoccluded IRA group (336 +/- 288 pg/ml) was significantly higher than that in the patent IRA group (116 +/- 106 pg/ml) at 1 month. BNP concentration decreased significantly at 6 months in the 2 groups (reoccluded IRA vs patent IRA 152 +/- 162 vs 44 +/- 58 pg/ml, p0.05). The increase in left ventricular volume from 1 to 6 months was significantly correlated with plasma BNP concentration at 1 month in the patent IRA group (r = 0.314, p0.01) and the reoccluded group (r = 0.634, p0.01). Linear regression analysis showed that the correlation between the 2 parameters in the 2 groups was similar. Based on stepwise multivariate linear regression analysis, only plasma BNP concentration was significantly correlated with the increase in left ventricular volume from 1 to 6 months in the 2 groups. In conclusion, these results suggest that plasma BNP concentration predicts left ventricular dilation independently of IRA patency.

G-protein-coupled receptor agonists including endothelin-1 (ET-1) and phenylephrine (PE) induce hypertrophy in neonatal ventricular cardiomyocytes. Others and we previously reported that Rac1 signaling pathway plays an important role in this agonist-induced cardiomyocyte hypertrophy. In this study reported here, we found that a Ca(2+)-sensitive non-receptor tyrosine kinase, proline-rich tyrosine kinase 2 (Pyk2)/cell adhesion kinase beta (CAKbeta), is involved in ET-1- and PE-induced cardiomyocyte hypertrophy medicated through Rac1 activation. ET-1, PE or the Ca(2+) inophore, ionomycin, stimulated a rapid increase in tyrosine phosphorylation of Pyk2. The tyrosine phosphorylation of Pyk2 was suppressed by the Ca(2+) chelator, BAPTA. ET-1- or PE-induced increases in [(3)H]-leucine incorporation and expression of atrial natriuretic factor and the enhancement of sarcomere organization. Infection of cardiomyocytes with an adenovirus expressing a mutant Pyk2 which lacked its kinase domain or its ability to bind to c-Src, eliminated ET-1- and PE-induced hypertrophic responses. Inhibition of Pyk2 activation also suppressed Rac1 activation and reactive oxygen species (ROS) production. These findings suggest that the signal transduction pathway leading to hypertrophy involves Ca(2+)-induced Pyk2 activation followed by Rac1-dependent ROS production.