Background-Apoptosis may contribute to the development of heart failure, but the role of apoptotic signaling initiated by the endoplasmic reticulum in this condition has not been well clarified. Methods and Results-In myocardial samples from patients with heart failure, quantitative real-time polymerase chain reaction revealed an increase in messenger RNA for C/EBP homologous protein (CHOP), a transcriptional factor that mediates endoplasmic reticulum-initiated apoptotic cell death. We performed transverse aortic constriction or sham operation on wild-type (WT) and CHOP-deficient mice. The CHOP-deficient mice showed less cardiac hypertrophy, fibrosis, and cardiac dysfunction compared with WT mice at 4 weeks after transverse aortic constriction, although the contractility of isolated cardiomyocytes from CHOP-deficient mice was not significantly different from that in the WT mice. In the hearts of CHOP-deficient mice, phosphorylation of eukaryotic translation initiation factor 2␣, which may reduce protein translation, was enhanced compared with WT mice. In the hearts of WT mice, CHOP-increased apoptotic cell death with activation of caspase-3 was observed at 4 weeks after transverse aortic constriction. In contrast, CHOP-deficient mice had less apoptotic cell death and lower caspase-3 activation at 4 weeks after transverse aortic constriction. Furthermore, the Bcl2/Bax ratio was decreased in WT mice, whereas this change was significantly blunted in CHOP-deficient mice. Real-time polymerase chain reaction microarray analysis revealed that CHOP could regulate several Bcl2 family members in failing hearts. Conclusions-We propose the novel concept that CHOP, which may modify protein translation and mediate endoplasmic reticulum-initiated apoptotic cell death, contributes to development of cardiac hypertrophy and failure induced by pressure overload. (Circulation. 2010;122:361-369.)

Natriuretic peptides enhance adiponectin production by human adipocytes in vitro and even in patients with CHF, which might have a beneficial effect on cardiomyocytes in patients receiving recombinant natriuretic peptide therapy for heart failure.

No abstract

These findings demonstrate that proteasome inhibition induces ER-initiated cardiomyocyte death via CHOP-dependent pathways without compensatory up-regulation of ER chaperones. Supplement and/or pharmacological induction of GRP78 can attenuate cardiac damage by proteasome inhibition.

No abstract

Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.

Objective-To determine whether cardiac iodine-123 metaiodobenzylguanidine ( 123 I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure. Design-Cardiac123 I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up. Setting-Tertiary referral centre. Patients-79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%. Results-There were 37 patients in group 1 (washout rate of > 27%) and 42 in group 2 (< 27%). During a follow up period of between 1 and 52 months, eight patients died suddenly and five died of worsening heart failure in group 1, while none died in group 2; 13 patients in group 1 and four in group 2 were admitted to hospital for progressive heart failure. Kaplan-Meier analysis showed that group 1 had a significantly higher mortality and morbidity (p = 0.001 and p < 0.001, respectively) than group 2. Conclusions-Cardiac 123

Background The efficacy of low‐voltage‐area ( LVA ) ablation has not been well determined. This study aimed to investigate the efficacy of LVA ablation in addition to pulmonary vein isolation on rhythm outcomes in patients with paroxysmal atrial fibrillation ( AF ). Methods and Results VOLCANO (Catheter Ablation Targeting Low‐Voltage Areas After Pulmonary Vein Isolation in Paroxysmal Atrial Fibrillation Patients) trial included paroxysmal AF patients undergoing initial AF ablation. Of 398 patients in whom a left atrial voltage map was obtained after pulmonary vein isolation, 336 (85%) had no LVA (group A). The remaining 62 (15%) patients with LVA s were randomly allocated to undergo LVA ablation (group B, n=30) or not (group C, n=32) in a 1:1 fashion. Primary end point was 1‐year AF ‐recurrence‐free survival rate. No adverse events related to LVA ablation occurred. Procedural (124±40 versus 95±33 minutes, P =0.003) and fluoroscopic times (29±11 versus 24±8 minutes, P =0.034) were longer in group B than group C. Patients with LVA s demonstrated lower AF ‐recurrence‐free survival rates (88%) than those without LVA (B, 57%, P <0.0001; C, 53%, P <0.0001). However, LVA ablation in addition to pulmonary vein isolation did not impact AF ‐recurrence‐free survival rate (group B versus C, P =0.67). Conclusions The presence of LVA was a strong predictor of AF recurrence after pulmonary vein isolation in patients with paroxysmal AF . However, LVA ablation had no beneficial impact on 1‐year rhythm outcomes. Registration URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000023403.