Thierry Couffinhal

Off-pump coronary artery bypass surgery in very high-risk patients: adjustment and preliminary results

Left ventricle dysfunction and comorbidities are responsible for a large number of complications after CABG. OPCAB could be an interesting alternative for very high-risk patients. Patients were included if EuroSCORE >9, or with at least two of the following criteria, severe LV dysfunction, recent myocardial infarction (MI), terminal renal failure, lung dysfunction, PVD, BMI>30. Patients were operated using the Octopus (Medtronic) system. One hundred and twenty patients, mean age 68+/-10 years, 72% male, were operated. Mean EuroSCORE was 10.2+/-5.3, LV function 36.79+/-11.3%, recent MI 57%, renal failure 52%, COPD 44%, PVD 52%, obesity 34%. Mean graft per patient was 2.1+/-0.8. Three patients underwent secondary PTCA treatment for incomplete revascularization. Combined surgery was required for 20%. Early mortality was 3%. Intensive care unit stay was 2.7 days. Early complications were: low output syndrome 3%, MI 0.8%, stroke 0.8%, kidney support 7%. Graft patency was systematically analyzed with MCTA or angiocardiography. OPCAB strategy seems to be safe and secure in this population of very high-risk patients reducing multi-organ failure. However, long-term results are needed to confirm this strategy.

Kif26b controls endothelial cell polarity through the Dishevelled/Daam1-dependent planar cell polarity–signaling pathway

An atypical kinesin, Kif26b, is identified as a signaling effector of the Wnt PCP under Daam1 signaling. Molecular evidence shows that it interacts with Dvl3/Daam1. Kif26b is involved in endothelial microtubule network stabilization and has a crucial role together with the Dvl3/Daam1 complex in establishing endothelial cell polarity.

Predictors of cardiovascular prognosis in patients receiving optimized secondary prevention measures after acute coronary syndrome

Background: After an acute coronary syndrome (ACS), optimal medical therapy (OMT) has been shown to be effective in reducing subsequent cardiovascular (CV) events. However, even in populations that reach recommended secondary prevention goals, there is a subset of patients that experience subsequent CV events. Aim: To identify biological or clinical predictors of residual risk of CV events in post-ACS patients receiving OMT. Patients and methods: A total of 990 post-ACS patients benefited from OMT (optimized treatment during the acute and chronic post-ACS phase, along with a therapeutic and dietary education programme). Traditional CV risk factors and atheroma disease markers (intima‐media thickness measurement, carotid atheroma, peripheral arterial disease (PAD) measured by ankle brachial index, and the number of coronary arteries with a >50% stenosis) were evaluated at 3 months post ACS. Cardiovascular events were recorded at follow up. Results: At 20-month follow up, >80% of the patients reached the recommended secondary prevention goals. In this population, diabetes was the only CV risk factor significantly associated with CV events in multivariate analysis including traditional risk factors (HR 1.61, p = 0.017). In multivariate analyses including CV risk factors and atheroma disease markers, only PAD remained significantly associated with CV events (HR 1.83, p = 0.04). The number of vascular beds involved was associated with poorer prognosis (HR for disease in 3-vascular-beds 3.85, p = 0.001, using disease in 1-vascular-bed as a reference group). Conclusion: In post-ACS patients with OMT, atheroma burden is a powerful prognostic marker of recurrent CV events, while diabetes remains the only independent marker of CV events among traditional CV risk factors.

Assessing cardiovascular risk factors after coronary artery bypass surgery: value of an aggressive strategy including systematic follow-up.

INTRODUCTION Coronary revascularization surgery is a palliative treatment modality which should not preclude efforts to treat atherosclerosis. AIM To assess ongoing cardiovascular risk factors after coronary artery bypass surgery and develop a strategy to attenuate such factors. METHODS 108 patients requiring a coronary artery bypass were included: 2 died soon after surgery and 6 were excluded for personal reasons. 100 patients were re-admitted into hospital 7 months after surgery for risk factor assessment. Eight months later, they were re-contacted by telephone (systematic follow-up) for a re-assessment. RESULTS The population consisted of 77 men with an average age of 64+/-11 years. Prior to the operation, the known risk factors were: smoking 34%; HBP 61%; cholesterol 47%; diabetes 30%; obesity 25%. During their hospital stay six months after the procedure: 91% of the patients had at least one lipid metabolism abnormality. New-onset diabetes was diagnosed in 5%. Blood pressure was uncontrolled in 18% and 10% were still smoking. Patients tended to be putting on weight and 55% engaged in little or no physical activity. Systematic follow-up: lipid metabolism had normalized in 70% of the patients. Blood glucose levels were significantly lower. Blood pressure was uncontrolled in 9% and 4% were still smoking. Their weight had stabilized and 65% were engaging in moderate-to-strenuous physical activity. CONCLUSION Inadequate attention is paid to risk factors after coronary artery bypass surgery. A short hospital stay including a cardiovascular evaluation and education about risk factors has a positive impact on the management of atherosclerosis in the medium term.

0297 : Targeting frizzled7 in endothelial cells: a novel approach to treat aberrant angiogenesis in proliferative retinopathy

Blinding diseases including retinopathy of prematurity and proliferative diabetic retinopathy are the consequence of pathological angiogenesis in the retina. A better understanding of the mechanisms involved in this abnormal proliferation of neovessels appears to be essential to develop drugs against new molecular targets. Recently, we have evidenced that Fzd7 receptor, a member of the Wnt/Fzd family, is required for retinal postnatal angiogenesis. This study aimed to investigate the role of Fzd7 during aberrant angiogenesis in a model of ischemic retinopathy. We used mice model of OIR to explore the involvement of Fzd7 during initial vaso-obliteration (VO) and subsequent neovascularization (NV) phases. By transgenic approaches, we observed that deletion of fzd7 in the endothelium ( fzd7 ECKO ) resulted in increased retinal tissue sensitivity to hypoxia during the VO phase of OIR. Moreover, fzd7 deletion in EC reduced the ectopic growth of pathologic neovessels into the vitreous during the NV phase (P17) demonstrating that Fzd7 was involved in pathological NV formation in mice retina during OIR. To determine how Fzd7 may regulate ischemic retinopathy, we explored canonical β-catenin and Notch signaling during OIR and showed that transcript expressions of lef1, axin2 and partners of Notch signaling were strongly decreased in fzd7 ECKO retina mice as compared to control. To evaluate therapeutic potential of Fzd7 blocking, we experimented 2 strategies: a monoclonal antibody (MabFzd7) and a soluble Fzd7 receptor (CRD domain). In vitro both MabFzd7 and Fzd7CRD decreased the activity of β-catenin reporter gene induced by Wnt3A in EC. In vivo intravitreal microinjection of MabFzd7 or intraperitoneal injection of Fzd7CRD in mice at P12 decreased neovessels in the treated eye compared to the control eye at P17. By controlling development of abnormal vascularization, Fzd7 could be a new target to develop promising anti-angiogenic drugs in the treatment of ischemic retinopathies. The author hereby declares no conflict of interest