Hybrid three-stage repair of mega-aortic syndrome with the Lupiae technique: 10-year results.

BACKGROUND: Mega-aortic syndrome (MAS) is a rare disease carrying a poor prognosis if treated conservatively. Open repairs of these aneurysms are invasive, while totally endovascular repairs are associated with higher rates of late reintervention due to endoleaks, compromising long-term prognosis. We describe the 10-year results of a hybrid three-stage approach to MAS using the Lupiae technique. METHODS: Between 2006 and 2016, 27 patients with MAS extending from the ascending aorta to the iliac arteries (MAS type III) underwent: (I) a surgical aortic arch debranching, using the Vascutek Lupiae™ multibranched graft to create a proximal Dacron landing zone; (II) an abdominal aorta debranching to create a distal Dacron landing zone and (III) the implantation of multiple endovascular stents to exclude any residual aneurysm between the two landing zones. RESULTS: One patient died following the first stage, and another following the second stage of the repair (overall mortality 7.4%). The interval between the first and the second stage was 58.3±16.1 days. The interval between the second and the third stage was 47.7±13.1 days. Four-year survival was 88.6%±6.2% while 10-year survival was 51.7%±17.9%. One patient had a type III endoleak after the third stage that self-resolved within 6 months without intervention. No patient had type I or II endoleaks and none underwent redo procedures. Mean follow-up was 5.9±3.6 years and completeness was 100%. CONCLUSIONS: Three-stage hybrid repairs using the Lupiae technique can be safely performed in MAS type III patients. Short intervals between the stages should mitigate the risk of rupture during the waiting periods and may enhance patient compliance, but to achieve this, the burden and the complexity of the first stage must be carefully weighted. Our strategy improves the long-term survival of these patients compared to their natural history and is less invasive than an open repair. The adoption of Dacron landing zones appears to be associated with very low rates of reintervention due to endoleaks.

Hybrid three-stage repair of mega aorta with Lupiae technique: tips and tricks.

Mega aorta syndrome (MAS) poses a complex clinical challenge: the involvement of the ascending aorta, aortic arch, descending thoracic and abdominal aorta with extension below the origin of renal arteries requires almost total replacement of the aorta. The modality of treatment remains still controversial. Different aortic debranching techniques have been developed to re-route the origin of epiaortic and visceral vessels and achieve an optimal landing zone for implantation of subsequent endovascular grafts. We illustrate the Lupiae technique as a further evolution of the aortic debranching and hybrid repair of a mega aorta. It was developed with the purpose to exclude a very long segment of diseased aorta by implanting two or more endoprostheses between two surgically-generated landing zones. We describe a series of 27 patients treated by this hybrid three-stage mega-aorta repair; the tips and tricks discussed here facilitate a safe and effective procedure, enable treatment of frail patients and help to avoid life-threatening complications.

Genetic determinants of on-clopidogrel high platelet reactivity.

Clopidogrel has been used (alone or in association with aspirin) to prevent vascular complications in atherothrombotic patients, to prevent stent thrombosis (ST) in patients undergoing percutaneous coronary intervention (PCI) and as a long-term prevention of cardiovascular and cerebrovascular events. Unfortunately, it is important to note that there are a number of patients who, during clopidogrel therapy, show and maintain a high platelet reactivity (PR), similar to that observed before the start of antiplatelet therapy. Clopidogrel pro-drug is absorbed in the intestine and this process is influenced by P-glycoprotein-1 (P-GP). Its conversion into 2-oxo clopidogrel is regulated by cytochromes (CYP) called CYP2C19, CYP2B6 and CYP1A2. Whereas, the final transformation into the active metabolite is regulated by CYP called CYP2C19, CYP2C9, CYP2B6, CYP3A4, CYP3A5 and, as recently emerged, by the glycoprotein paraoxonase-1 (PON1). The genes encoding these enzymes are characterized by several polymorphisms. Some of these are able to modify the activity of proteins, reducing the concentration of active metabolite and the values of on-clopidogrel PR. Only one gene polymorphism (CYP2C19*17) increases the clopidogrel metabolization and so the clopidogrel-induced platelet inhibition. Several studies have clearly associated these gene polymorphisms to both ischemic and bleeding complications in patients receiving dual antiplatelet therapy. The aim of this review is to describe the principal gene polymorphisms influencing on-clopidogrel PR and their relationship with long-term clinical outcome.

Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome.

OBJECTIVES: This study sought to investigate the evolving pattern over time of on-clopidogrel platelet reactivity (PR) and its relationship with genotype and clinical outcomes after percutaneous coronary intervention. BACKGROUND: Whether on-clopidogrel PR and role of genotype differ over time is unknown. METHODS: On-clopidogrel PR before percutaneous coronary intervention, and 1 and 6 months thereafter via VerifyNow P2Y12 (Accumetrics Inc., San Diego, California), CYP2C19*2, *17, CYP3A5*3, and ABCB1 polymorphisms were evaluated in 300 patients. Death, stroke, myocardial infarction, and bleedings were assessed up to 1 year. RESULTS: On-clopidogrel PR varied significantly over time, being higher at baseline than at 1 and 6 months after. From baseline to 1 month, 83 of 300 patients varied their response status. This was mainly due to baseline poor responders becoming full responders (75 of 83). Genotype justifies roughly 18% of this trend. CYP2C19*2 and *17 influence on PR was consistent over time, whereas that of ABCB1 appeared of greater impact at baseline. On-clopidogrel PR at 1 month independently best predicts ischemic and bleeding events. We found a therapeutic window (86 to 238 P2Y12 reactivity units) with a lower incidence of both ischemic and bleeding complications. A risk score was created by combining genotype (ABCB1 and CYP2C19*2), baseline PR, and creatinine clearance to predict 1-month poor responsiveness and 1-year poor prognosis. CONCLUSIONS: In patients at steady state for clopidogrel undergoing percutaneous coronary intervention, PR decreases from baseline to 1 month. Genotype influences ≈18% of this trend. On-clopidogrel PR at 1 month is the strongest predictor of adverse outcomes, and this can be predicted by combining genotype to baseline phenotype and clinical variables.

ACE inhibition modulates endothelial apoptosis and renewal via endothelial progenitor cells in patients with acute coronary syndromes.

BACKGROUND: The equilibrium between endothelial apoptosis and endothelial renewal is altered in acute coronary syndromes and may be related to differences in the beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists (angiotensin receptor blockers). METHODS: We evaluated the effect of treatment on endothelial function in post-myocardial infarction (MI) patients treated with perindopril (group 2, n = 16) or valsartan (group 3, n = 17) at baseline and after 7, 15, and 30 days and in normal controls (group 1, n = 20). Endothelial apoptosis was determined by cultivating serum samples in vitro with human umbilical vein endothelial cells (HUVECs), while endothelial renewal was assessed by mobilization of CD34+ bone marrow cells. RESULTS: At baseline, post-MI patients had significantly elevated rates of apoptosis (16.6 ± 5.0% and 16.5 ± 8.4% in groups 2 and 3, respectively [both p = 0.01] vs 1.6 ± 0.7% in group 1), which declined in group 2 (10.5 ± 4.4% at 30 days, p = 0.04), but not in group 3. Similar results and trends were found for the Bax/Bcl-2 ratio. CD34+ mobilization was significantly increased in group 2 (3.0 ± 1.0 at baseline to 6.2 ± 1.6 at 15 days, p = 0.03), whereas in group 3 CD34+ mobilization did not change significantly. The findings in group 2 were accompanied by an increase in vascular endothelial growth factor at 15 days, and a reduction in tumor necrosis factor-α and its soluble receptors, versus no change in group 3. Similar findings were observed for angiotensin II and bradykinin. CONCLUSION: Our results indicate that perindopril, but not valsartan, reduces the proapoptotic effect of serum on the endothelium and increases endothelial renewal in patients with acute coronary syndromes.