Alejandro Diego

La reestenosis en el stent depende del daño vascular inducido. ¿Son válidos los modelos experimentales actuales de análisis de los stents farmacoactivos?

INTRODUCTION AND OBJECTIVES Drug-eluting stents are useful for preventing restenosis, but the patho-physiological processes involved in the proliferative response after implantation are still not known in detail. The aim of this study is to compare the coronary vascular histomorphometry after implanting drug-eluting stents and bare metal stents in a swine model. METHODS Sixty stents were randomly implanted in 20 Large White female pigs with a ratio of baremetal/drug-eluting stents of 1:2. After 28 days, euthanasia and histomorphometry were performed. We defined the vessel injury score in accordance to whether the internal elastic lamina was intact or ruptured. RESULTS There were no differences between drug-eluting stents and bare metal stents in the intact internal elastic lamina group regarding neointimal area or % restenosis (1.3 [1.1-2.2]) vs 2.0 [1.3-2.5] mm²; P=.6; and 14.0 [12.1-20.8] vs 22.2 [14.1-23.3] %; P=.5). We assessed statistically significant differences for the ruptured internal elastic lamina group, (neointimal area 1.2 [0.8-2.0] vs 2.9 [2.3-3.7] mm²; P=.001 and % restenosis 16.63 [11.2-23.5] vs 30.4 [26.4-45.7] %; P=.001). CONCLUSIONS In our swine model, we did not find any differences between proliferative response of drug-eluting stents and bare metal stents when the internal elastic lamina is intact; differences are only found when vascular injury is deeper.

Preclinical Evaluation of Coronary Stents: Focus on Safety Issues

In recent years, we have witnessed a revolution in the treatment of coronary artery disease. The development and improvement of drug eluting stents (DES) have lowered the incidence of restenosis to one-digit figures. In the search for a superior efficacy, animal models have played a key role. The classical swine model of coronary stenting remains the preferred model to measure restenosis, although the rabbit iliac artery stenting has become an accepted alternative. After widespread clinical use of DES, an unforeseen complication arose: late stent thrombosis. In a back-to-bench step, some data from animal models helped to explain the phenomenon. A delayed and incomplete vascular healing was detected. Toxic and hypersensitivity reactions to polymers and/or drugs seem to be the underlying causes. So, translational research focused on the safety aspect of these devices: development of better drug carriers as absorbable polymers or fully bioresorbable scaffolds, selection of different drugs and assessment of the re-endothelialization process. We review and evaluate the efficacy and safety of coronary stents in different animal models. Further improvements in this field such as, the selection of better animal models (e.g. hyperlipidemic, diabetic, atherosclerotic) that closely mimic the clinical setting and longer follow-up periods to detect late complications are also discussed.

P2Y12 platelet reactivity after thrombolytic therapy for ST-segment elevation myocardial infarction

INTRODUCTION Thrombolysis, as reperfusion therapy for ST segment elevation myocardial infarction (STEMI), induces a pro-thrombotic status with enhanced platelet activity; this study aims to evaluate P2Y12 platelet reactivity and response to clopidogrel in the post-thrombolysis scenario. MATERIALS AND METHODS Observational, prospective study, including consecutive patients with elective angiography after thrombolytic therapy for STEMI. Every patient received antiplatelet therapy with loading doses of 250 mg aspirin and 300 mg clopidogrel on admission followed by 100mg aspirin and 75 mg clopidogrel daily. P2Y12-dependent platelet reactivity (expressed in P2Y12-Reaction Units, PRU) was assessed with VerifyNow® device on admission, daily after thrombolysis and pre-angiography. RESULTS 41 patients fulfilled the inclusion criteria. Median time between thrombolysis and angiography was 2,5 days (IQR 1,8-4,1). Post-treatment platelet reactivity (PPR) showed poor correlation with time on clopidogrel treatment (r2=0.04) and reached a maximum value of 274 ± 84 PRU during the first 24h after thrombolysis (Day +1 determination). After this, values showed a progressive reduction until the point of angiography (249 ± 82 PRU), without significant differences between consecutive time-points (p=0,549). Inhibition of platelet aggregation (IPA) assessed as a percentage of P2Y12 receptor blockage was poor, increasing gradually from 0 ± 4% on admission to 11 ± 6% the day of the angiography (p=0,001). 71,4% of patients showed PPR ≥ 208 PRU during angiography. CONCLUSIONS Platelet reactivity, as assessed by post-treatment P2Y12 mediated reactivity, is heightened after thrombolytic therapy during STEMI management. In this scenario, standard doses of clopidogrel did not achieve significant inhibition of ADP-mediated platelet reactivity.

Primary Angioplasty in Patients Older Than 75 Years. Profile of Patients and Procedures, Outcomes, and Predictors of Prognosis in the ESTROFA IM + 75 Registry

INTRODUCTION AND OBJECTIVES The proportion of elderly patients undergoing primary angioplasty is growing. The present study describes the clinical profile, procedural characteristics, outcomes, and predictors of outcome. METHODS A 31-center registry of consecutive patients older than 75 years treated with primary angioplasty. Clinical and procedural data were collected, and the patients underwent clinical follow-up. RESULTS The study included 3576 patients (39.3% women, 48.5% with renal failure, 11.5% in Killip III or IV, and 29.8% with>6hours of chest pain). Multivessel disease was present in 55.4% and nonculprit lesions were additionally treated in 24.8%. Radial access was used in 56.4%, bivalirudin in 11.8%, thromboaspiration in 55.9%, and drug-eluting stents in 26.6%. The 1-month and 2-year incidences of cardiovascular death were 10.1% and 14.7%, respectively. The 2-year rates of definite or probable thrombosis, repeat revascularization, and BARC bleeding>2 were 3.1%, 2.3%, and 4.2%, respectively. Predictive factors were diabetes mellitus, renal failure, atrial fibrillation, delay to reperfusion>6hours, ejection fraction<45%, Killip class III-IV, radial access, bivalirudin, drug-eluting stents, final TIMI flow of III, and incomplete revascularization at discharge. CONCLUSIONS Notable registry findings include frequently delayed presentation and a high prevalence of adverse factors such as renal failure and multivessel disease. Positive procedure-related predictors include shorter delay, use of radial access, bivalirudin, drug-eluting stents, and complete revascularization before discharge.

Influence of platelet reactivity and response to clopidogrel on myocardial damage following percutaneous coronary intervention in patients with non-st-segment elevation acute coronary syndrome☆

INTRODUCTION A wide variability in the response to clopidogrel and magnitude of post-treatment platelet reactivity has been described. However, this has been demonstrated by light transmittance aggregometry, a method too laborious for daily practice. Point-of-care devices may overcome this limitation, but little is known on the predictive value of such measurements. Our objective was to determine the relationship between platelet reactivity and the incidence of myocardial damage following percutaneous coronary intervention (PCI) in patients with Non-ST-segment Elevation Acute Coronary Syndrome (NSTEACS). MATERIALS AND METHODS This prospective study included 93 patients with NSTEACS and PCI. All patients received a loading dose of 300 mg of clopidogrel and 250 mg of aspirin. Myocardial damage was defined as any elevation above upper limit of normal or previous levels of troponin T, assessed every 6 h for at least 24 h following PCI. Platelet reactivity not related to clopidogrel (BASE reactivity), related to P2Y12 inhibition (P2Y12 reactivity) and inhibition of platelet aggregation (IPA) were assessed immediately pre-PCI with the VerifyNow device. RESULTS Myocardial damage was detected in 60 patients (64.5%). Higher BASE reactivity was associated with myocardial damage (287.8+/-62.6 vs. 260+/-55.9 units, p=0.043) while a trend was found for P2Y12 reactivity (173.4+/-70.3 vs. 149.2+/-58.4 units, p=0.109). No relationship was detected for IPA. Multivariate logistic regression analysis confirmed that BASE reactivity (p=0.04) and P2Y12 reactivity (p=0.03) were independent predictors of myocardial damage. CONCLUSIONS Platelet reactivity before PCI appears to be better predictor of myocardial damage than does response to clopidogrel.

Platelet Reactivity and Stent Thrombosis: Still Some Issues to Solve

We read with great interest the recent article by Sibbing et al. ([1][1]). They concluded that low response to clopidogrel assessed with multiple electrode platelet aggregometry (MEA) is significantly associated with an increased risk of stent thrombosis. Considering the potential clinical

Mitral valve prosthesis implanted in atrial wall over huge calcified annulus

We describe an alternative technique for mitral valve replacement in patients with severe mitral annular calcification, in whom conventional techniques are not feasible. A new annulus that allows supra-annular prosthetic implantation is created.

Multivessel disease in patients over 75 years old with ST elevated myocardial infarction. Current management strategies and related clinical outcomes in the ESTROFA MI + 75 nation-wide registry

BACKGROUND In elderly patients with ST elevated myocardial infarction (STEMI) and multivessel disease (MVD the outcomes related with different revascularization strategies are not well known. METHODS Subgroup-analysis of a nation-wide registry of primary angioplasty in the elderly (ESTROFA MI+75) with 3576 patients over 75years old from 31 centers. Patients with MVD were analyzed to describe treatment approaches and 2years outcomes. RESULTS Of 1830 (51%) with MVD, 847 (46%) underwent multivessel revascularization either in acute (51%), staged (44%) or both procedures (5%). Patients with previous myocardial infarction and those receiving drug-eluting stents or IIb-IIIa inhibitors were more prone to be revascularized, whereas older patients, females and those with Killip III-IV, renal failure and higher ejection fraction were less likely. Survival free of cardiac death and infarction at 2years was better for those undergoing multivessel PCI (85.8% vs. 80.4%, p<0.0008), regardless of Killip class. Multivessel PCI was protective of cardiac death and infarction (HR 0.60, 95% CI 0.40-0.89; p=0.011). Complete revascularization made no difference in outcomes among those patients undergoing multivessel PCI. The best prognosis corresponded to those undergoing multivessel PCI in staged procedures (p<0.001). A propensity score matching analysis (514 patients in each group) yielded similar results. CONCLUSIONS In elderly patients with STEMI and MVD, multivessel PCI was related with better outcomes especially after staged procedures. Among those undergoing multivessel PCI, anatomically defined completeness of revascularization had not prognostic influence. SUMMARY We sought to investigate the revascularization strategies applied and their prognostic implications in patients aged over 75years with ST elevated myocardial infarction showing multivessel disease. Of 1830 patients, 847 (46%) underwent multivessel PCI either in acute (51%), staged (44%) or both procedures (5%). Multivessel PCI was independent predictor of cardiac death and infarction with the best prognosis corresponding to those undergoing staged procedures.

Placement of a Rigid Tricuspid Annuloplasty Ring Over a Flexible Ring for the Treatment of Recurrent Tricuspid Regurgitation

Abstract  We describe a technique that implants a rigid tricuspid annuloplasty ring over a previously inserted flexible ring for the treatment of recurrent tricuspid regurgitation. This technique avoids the trauma associated with the excision of a flexible ring in patients with friable annular tissue. (J Card Surg 2012;27:549‐550)

TCT-564 Biodegradable-Polymer Biolimus Eluting Stents Show Better Antiproliferative Efficacy And Vascular Healing Pattern Than Permanent-Polymer Paclitaxel Eluting Stents in a Preclinical Coronary Model

Background: Second-generation drug eluting stents (DES) have shown a high efficacy in terms of restenosis prevention, like first-generation DES, with reduced rates of stent thrombosis, especially late stent thrombosis. The suggested mechanism for this superiority is a better morphological and functional healing response. The objective of this study is to compare the efficacy and safety results of 2 different, first and second-generation, DES in a swine model of normal coronary arteries. Methods: In 9 domestic juvenile swine (25 3 kg), one stent per coronary artery was implanted with an intended stent-to-artery ratio 1.1. We used 9 bare metal stents (BMS), 9 permanent-polymer paclitaxel eluting stents (PES) and 9 biodegradable-polymer biolimus eluting stents (BES). Quantitative coronary angiography was performed after 28 days to assess the in-stent % stenosis and the endothelium-dependent vasomotor response of the distal vessel (Acetylcholine 10-6M). We performed morphometric analyses of the in-stent % area stenosis and the endothelialization rate (haematoxylin-eosin stain, extent of luminal surface coverage with endothelial cells) at 3 levels of each stent sample. The eNOS endothelialization index measures the proportion of the whole luminal surface covered by eNOS endothelial cells. Results: All the stents were implanted as per-protocol, with a final stent:artery ratio 1.17 0.15. No baseline differences were observed between groups. The Table shows the restenosis and the functional healing parameters analyzed in each group.