INTRODUCTION: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare cardiomyopathy, originally described as an isolated disease without other structural cardiac abnormalities. The aim of this study was to explore the prevalence of LVNC among adults with different types of congenital heart disease. METHODS: From our databases we identified adults with congenital heart disease who fulfilled diagnostic criteria for LVNC. We report frequencies of associated congenital cardiac defects and the prevalence of LVNC among patients with different congenital heart defects. RESULTS: From a total of 202 patients with LVNC, 24 patients (12%; mean age 32±11years, 19 males) had additional congenital cardiac defects. Associated defects were left ventricular outflow tract abnormalities in 11 patients (46%), including 7 uni-or bicuspid aortic valves; two aortic coarctations; one diffuse aortic hypoplasia and one subaortic stenosis, Ebstein anomaly in 6 patients (25%), tetralogy of Fallot in two (8%), and double outlet right ventricle in one patient (4%). In our cohort, the prevalence of LVNC was highest among patients with Ebstein anomaly (6/40, 15%), followed by aortic coarctation (2/60, 3%), tetralogy of Fallot (3/129, 2%) and uni-or bicuspid aortic valves (7/963, 1%). CONCLUSION: In adults, various forms of congenital heart disease are associated with LVNC, particularly stenotic lesions of the left ventricular outflow tract, Ebstein anomaly, and tetralogy of Fallot. In the future, studying these patients in more depth may provide a better understanding of the interplay between genetic and hemodynamic factors that lead to the phenotype of LVNC.

Carbamylation of LDL induces endothelial dysfunction via LOX-1 activation and increased ROS production leading to eNOS uncoupling. This indicates a novel mechanism in the pathogenesis of atherosclerotic disease which may be pathogenic and prognostic in patients with CKD and high plasma levels of cLDL.

Abstract-Paclitaxel is used on drug-eluting stents because it inhibits proliferation of vascular cells. Stent thrombosis remains a concern with this compound, particularly with higher dosages. This study investigates the effect of paclitaxel on tissue factor (TF) expression in human endothelial cells. Paclitaxel enhanced thrombin-induced endothelial TF protein expression in a concentration-and time-dependent manner. A concentration of 10 Ϫ5 mol/L elicited a 2.1-fold increase in TF protein and a 1.6-fold increase in TF surface activity. The effect was similar after a 1 hour as compared with a 25-hour pretreatment period. Real-time polymerase chain reaction revealed that paclitaxel increased thrombininduced TF mRNA expression. Paclitaxel potently activated c-Jun terminal NH 2 kinase (JNK) as compared with thrombin alone, whereas the thrombin-mediated phosphorylation of p38 and extracellular signal-regulated kinase remained unaffected. Similar to paclitaxel, docetaxel enhanced both TF expression and JNK activation as compared with thrombin alone. The JNK inhibitor SP600125 reduced thrombin-induced TF expression by 35%. Moreover, SP600125 blunted the effect of paclitaxel and docetaxel on thrombin-induced TF expression. Paclitaxel increases endothelial TF expression via its stabilizing effect on microtubules and selective activation of JNK. This observation provides novel insights into the pathogenesis of thrombus formation after paclitaxel-eluting stent deployment and may have an impact on drug-eluting stent design. Key Words: acute coronary syndrome Ⅲ thrombosis Ⅲ stents Ⅲ MAP kinase Ⅲ signal transduction P ercutaneous intervention is common practice for treating acute coronary syndromes. 1,2 Drug-eluting stents (DES), which are coated with antiproliferative agents, improve the outcome after coronary artery stenting. 3 Paclitaxel, a microtubule-stabilizing drug eliciting cell cycle arrest in G 2 /M phase, is used on DES because it reduces vascular smooth muscle cell proliferation and migration. 4 Several randomized clinical trials have demonstrated that paclitaxeleluting stents decrease intimal hyperplasia and restenosis, leading to reduced rates of major adverse cardiac events as compared with bare-metal stents (BMS). 3,[5][6][7] In contrast, the use of DES has not reduced the occurrence of stent thrombosis as compared with BMS. 3,5,[7][8][9] Acute, subacute, and late in-stent thromboses have been observed in patients treated with paclitaxel-eluting stents, particularly following cessation of clopidogrel therapy. 8,10 -12 Moreover, the SCORE trial, which analyzed the effect of a stent releasing higher paclitaxel concentrations than the TAXUS stent, had to be terminated because of increased rates of in-stent thrombosis. 13

ObjectiveWe investigated the benefit of Impella, a modern percutaneous mechanical support (pMCS) device, versus former standard intra-aortic balloon pump (IABP) in acute myocardial infarction complicated by cardiogenic shock (AMICS).MethodsThis single-centre, retrospective study included patients with AMICS receiving pMCS with either Impella or IABP. Disease severity at baseline was assessed with the IABP-SHOCK II score. The primary outcome was all-cause mortality at 30 days. Secondary outcomes were parameters of shock severity at the early postimplantation phase. Adjusted Cox proportional hazards models identified independent predictors of the primary outcome.ResultsOf 116 included patients, 62 (53%) received Impella and 54 (47%) IABP. Despite similar baseline mortality risk (IABP-SHOCK II high-risk score of 18 % vs 20 %; p = 0.76), Impella significantly reduced the inotropic score (p < 0.001), lactate levels (p < 0.001) and SAPS II (p =0.02) and improved left ventricular ejection fraction (p = 0.01). All-cause mortality at 30 days was similar with Impella and IABP (52 % and 67 %, respectively; p = 0.13), but bleeding complications were more frequent in the Impella group (3 vs 4 units of transfused erythrocytes concentrates due to bleeding complications, p = 0.03). Previous cardiopulmonary resuscitation (HR 3.22, 95% CI 1.76 to 5.89; p < 0.01) and an estimated intermediate (HR 2.77, 95% CI 1.42 to 5.40; p < 0.01) and high (HR 4.32 95% CI 2.03 to 9.24; p = 0.01) IABP-SHOCK II score were independent predictors of all-cause mortality.ConclusionsIn patients with AMICS, haemodynamic support with the Impella device had no significant effect on 30-day mortality as compared with IABP. In these patients, large randomised trials are warranted to ascertain the effect of Impella on the outcome.

Our data provide pharmacological and genetic evidence that endogenous PARP1 is required for atherogenesis in vivo by increasing adhesion molecules with endothelial activation, enhancing inflammation, and inducing features of plaque vulnerability. Thus, inhibition of PARP1 may represent a promising therapeutic target in atherosclerosis.

This is the first study performing profiling and validation of miRNAs that are associated with adverse cardiovascular outcome in patients with STEMI. MiR-26b-5p, miR-320a, and miR-660-5p discriminated for MACE and increased risk prediction when added to the GRACE score and a clinical model. These findings suggest that the release of specific miRNAs into circulation may reflect the activation of molecular pathways that impact on clinical outcome after STEMI.

Aims  Acute coronary syndromes with intact fibrous cap (IFC-ACS), i.e. caused by coronary plaque erosion, account for approximately one-third of ACS. However, the underlying pathophysiological mechanisms as compared with ACS caused by plaque rupture (RFC-ACS) remain largely undefined. The prospective translational OPTICO-ACS study programme investigates for the first time the microenvironment of ACS-causing culprit lesions (CL) with intact fibrous cap by molecular high-resolution intracoronary imaging and simultaneous local immunological phenotyping. Methods and results  The CL of 170 consecutive ACS patients were investigated by optical coherence tomography (OCT) and simultaneous immunophenotyping by flow cytometric analysis as well as by effector molecule concentration measurements across the culprit lesion gradient (ratio local/systemic levels). Within the study cohort, IFC caused 24.6% of ACS while RFC-ACS caused 75.4% as determined and validated by two independent OCT core laboratories. The IFC-CL were characterized by lower lipid content, less calcification, a thicker overlying fibrous cap, and largely localized near a coronary bifurcation as compared with RFC-CL. The microenvironment of IFC-ACS lesions demonstrated selective enrichment in both CD4+ and CD8+ T-lymphocytes (+8.1% and +11.2%, respectively, both P &lt; 0.05) as compared with RFC-ACS lesions. T-cell-associated extracellular circulating microvesicles (MV) were more pronounced in IFC-ACS lesions and a significantly higher amount of CD8+ T-lymphocytes was detectable in thrombi aspirated from IFC-culprit sites. Furthermore, IFC-ACS lesions showed increased levels of the T-cell effector molecules granzyme A (+22.4%), perforin (+58.8%), and granulysin (+75.4%) as compared with RFC plaques (P &lt; 0.005). Endothelial cells subjected to culture in disturbed laminar flow conditions, i.e. to simulate coronary flow near a bifurcation, demonstrated an enhanced adhesion of CD8+T cells. Finally, both CD8+T cells and their cytotoxic effector molecules caused endothelial cell death, a key potential pathophysiological mechanism in IFC-ACS. Conclusions  The OPTICO-ACS study emphasizes a novel mechanism in the pathogenesis of IFC-ACS, favouring participation of the adaptive immune system, particularly CD4+ and CD8+ T-cells and their effector molecules. The different immune signatures identified in this study advance the understanding of coronary plaque progression and may provide a basis for future development of personalized therapeutic approaches to ACS with IFC. Trial registration The study was registered at clinicalTrials.gov (NCT03129503).

In most patients with PH and AS, TAVR is associated with a significant early and late reduction of PASP. Patients with reversible PH after TAVR are at lower risk of all-cause mortality at early, mid-, and long-term follow-up. Therefore, the presence of PH should not preclude treatment with TAVR.