BackgroundIn chronic liver disease, hepatic stellate cells (HSC) transdifferentiate into myofibroblasts, promoting extracellular matrix (ECM) synthesis and deposition. Stimulation of HSC by transforming growth factor-β (TGF-β) is a crucial event in liver fibrogenesis due to its impact on myofibroblastic transition and ECM induction. In contrast, hepatocyte growth factor (HGF), exerts antifibrotic activities. Recently, miR-29 has been reported to be involved in ECM synthesis. We therefore studied the influence of HGF and TGF-β on the miR-29 collagen axis in HSC.MethodologyHSC, isolated from rats, were characterized for HGF and Met receptor expression by Real-Time PCR and Western blotting during culture induced myofibroblastic transition. Then, the levels of TGF-β, HGF, collagen-I and -IV mRNA, in addition to miR-29a and miR-29b were determined after HGF and TGF-β stimulation of HSC or after experimental fibrosis induced by bile-duct obstruction in rats. The interaction of miR-29 with 3′-untranslated mRNA regions (UTR) was analyzed by reporter assays. The repressive effect of miR-29 on collagen synthesis was studied in HSC treated with miR-29-mimicks by Real-Time PCR and immunoblotting.Principal FindingsThe 3′-UTR of the collagen-1 and −4 subtypes were identified to bind miR-29. Hence, miR-29a/b overexpression in HSC resulted in a marked reduction of collagen-I and -IV synthesis. Conversely, a decrease in miR-29 levels is observed during collagen accumulation upon experimental fibrosis, in vivo, and after TGF-β stimulation of HSC, in vitro. Finally, we show that during myofibroblastic transition and TGF-β exposure the HGF-receptor, Met, is upregulated in HSC. Thus, whereas TGF-β stimulation leads to a reduction in miR-29 expression and de-repression of collagen synthesis, stimulation with HGF was definitely associated with highly elevated miR-29 levels and markedly repressed collagen-I and -IV synthesis.ConclusionsUpregulation of miRNA-29 by HGF and downregulation by TGF-β take part in the anti- or profibrogenic response of HSC, respectively.

AimsData on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro–B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline.Methods and resultsHeart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23–0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23–1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28–36%; P<0.001), NT-proBNP (2771–1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11–0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16–0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients.ConclusionLeft bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome.

We found that, although feasible as an acute salvage option, SA distinctively increases post-procedural midterm MACE and mortality rates. This places emphasis on the importance of avoiding eventual SA situations, underlining the importance of ample lesion preparation prior to stent implantation.

IntroductionAcute, total occlusion of the unprotected left main stem (uLMo) in acute coronary syndrome (ACS) patients is a catastrophic event often accompanied by sudden cardiac death (SCD) and/or cardiogenic shock (CS) with high mortality rates and limited methods of successful treatment. Emergent, surgical and percutaneous revascularization has been reported before, yet comprehensive data remains scarce.AimTo examine emergency percutaneous coronary intervention (PCI) outcomes in ACS cases presenting with uLMo.Material and methodsData on 23 subjects undergoing primary PCI in uLMo cases were analyzed. The primary end-point was in-hospital death; secondary end-points were successful salvage of coronary anatomy and 90-day major cardiac adverse events (MACE).ResultsAbout 40% of LM occlusion cases presented following successful on-site cardio-pulmonary resuscitation (CPR). Of all patients arriving for treatment the occluded LM was successfully opened and stented in ~90% of cases. CS was present in > 85% of cases, and circulatory support in the form of intra-aortic balloon pump and/or extracorporeal membrane oxygenation systems was applied in every eligible case (~80%). The in-hospital death rate was 56%, mostly including individuals requiring prior CPR. At 6 months, additional MACE rates were low at 8.7%.ConclusionsWe found that uLMo ACS cases often present with preceding CPR and mostly in manifest CS. Coronary salvage is generally successful, yet uLMo even with optimal present day complex treatment yields quite high mortality rates. This is especially true for patients receiving prior CPR. In surviving patients, however, 6-month MACE rates are acceptable.

BACKGROUND Despite technical advancements, implantation of coronary sinus (CS) leads may be challenging, and dislocation remains a relevant clinical problem.OBJECTIVE The aim of this study was to investigate the effectiveness, safety, and long-term outcome of stent implantation to anchor the lead to the wall of the CS side branch. METHODSStenting of a CS side branch was performed in 312 patients. The procedure was performed because of postoperative lead dislocation in 16 patients and because of an intraoperative unstable lead position or phrenic nerve stimulation in 296 cases. A bare metal coronary stent was introduced over a second guide wire in the same CS sheath. The stent was deposited 5-35 mm proximal to the most proximal electrode. Mechanical damage of the CS side branch or pericardial effusion was not observed owing to stenting. RESULTSDuring follow-up (median 28.4, interquartile range 15-37, maximum 70 months), a clinically important increase in the left ventricular pacing threshold was found in four cases and reoperation was necessary in only two patients (0.6%). Phrenic nerve stimulation was observed in 18 instances, and repositioning with an ablation catheter was performed in seven cases. Impedance measurements did not suggest lead insulation failure. Three stented leads were extracted without complication after 3-49 months owing to infection, while four leads were extracted easily during heart transplantation after 7-27 months.CONCLUSION Stent implantation to stabilize CS lead position seems to be an effective and safe procedure in prevention and treatment of CS lead dislocation in selected cases.KEYWORDS Cardiac resynchronization; LV lead implantation; Coronary sinus; Lead dislocation; Stent implantation ABBREVIATIONS CRT ϭ cardiac resynchronization therapy; CS ϭ coronary sinus; INR ϭ international normalized ratio; LV ϭ left ventricle; NYHA ϭ New York Heart Association; PNS ϭ phrenic nerve stimulation (Heart Rhythm 2011;8:845-850)