Luc Bilodeau

Probucol and Multivitamins in the Prevention of Restenosis after Coronary Angioplasty

BACKGROUND Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty. METHODS One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach. RESULTS The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol). CONCLUSIONS The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Biocompatibility aspects of new stent technology

Stent implantation represents a major step forward since the introduction of coronary angioplasty. As indications continue to expand, better understanding of the early and late biocompatibility issues appears critical. Persisting challenges to the use of intracoronary stents include the prevention of early thrombus formation and late neointima development. Different metals and designs have been evaluated in animal models and subsequently in patients. Polymer coatings have been proposed to improve the biocompatibility of metallic stents or to serve as matrix for drug delivery and they are currently undergoing clinical studies. The promises of a biodegradable stent have not yet been fulfilled although encouraging results have recently been reported. Continuous low dose-rate brachytherapy combining the scaffolding effect of the stent with localized radiation therapy has witnessed the development and early clinical testing of radioactive stents. The combined efforts of basic scientists and clinicians will undoubtedly contribute to the improvement of stent biocompatibility in the future.

Randomized Comparison of Primary Percutaneous Coronary Intervention With Combined Proximal Embolic Protection and Thrombus Aspiration Versus Primary Percutaneous Coronary Intervention Alone in ST-Segment Elevation Myocardial Infarction: The PREPARE (PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation) Study

OBJECTIVES The purpose of this study was to evaluate the effectiveness of combined proximal embolic protection with thrombus aspiration (Proxis Embolic Protection System [St. Jude Medical, St. Paul, Minnesota]) in ST-segment elevation myocardial infarction patients. BACKGROUND Embolization during primary percutaneous coronary intervention (PCI) may result in microvascular obstruction, reduced myocardial perfusion, and impaired prognosis. METHODS Two hundred eight-four patients were randomized to primary PCI with the Proxis system versus primary PCI alone after angiography. The primary end point was the occurrence of complete (> or =70%) ST-segment resolution (STR) at 60 min measured by continuous ST-segment Holter. RESULTS There was no significant difference in the occurrence of the primary end point (80% vs. 72%, p = 0.14). However, immediate complete STR (at time of last contrast) occurred in 66% of Proxis-treated patients and 50% in control patients (absolute difference, 16.3%; 95% confidence interval: 4.3% to 28.2%; p = 0.009). A significant lower ST-segment curve area (0 to 3 h after primary PCI) was observed in the Proxis arm (5,192 microV/min vs. 6,250 microV/min, p = 0.037). Major adverse cardiac and cerebral events at 30 days occurred with similar frequency in both groups (6 vs. 10). CONCLUSIONS There was no significant difference in complete STR at 60 min in this proof-of-concept study. However, we observed a significant difference in immediate complete STR in Proxis-treated patients, better STR at later time points, and a reduction of electrocardiogram injury current over time, compared with control patients. The results suggest that primary PCI with the Proxis system may lead to better immediate microvascular flow in ST-segment elevation myocardial infarction patients. (The PREPARE Study; ISRCTN71104460).

Treatment of functional mitral valve regurgitation with the permanent percutaneous transvenous mitral annuloplasty system: Results of the multicenter international Percutaneous Transvenous Mitral Annuloplasty System to Reduce Mitral Valve Regurgitation in Patients with Heart Failure trial

OBJECTIVES PTOLEMY-2 was a prospective multicenter phase I single-arm feasibility trial to evaluate the second-generation permanent percutaneous transvenous mitral annuloplasty (PTMA) device in reducing functional mitral regurgitation (MR). BACKGROUND Percutaneous MR reduction has been performed through a direct method of clipping and securing the mitral leaflets together or an indirect approach of reducing mitral annular dimension via the coronary sinus. The PTMA device is the only coronary sinus mitral repair device without a static fixation element. METHODS Patients with at least moderate functional MR, New York Heart Association functional class II to IV, and left ventricular ejection fraction of 20% to 50% were enrolled at 14 centers in 5 countries. Device effects on patients were assessed by serial echocardiography, quality of life (QOL), and exercise capacity metrics. RESULTS A total of 43 patients were recruited, and 30 patients (70%) were implanted with a permanent PTMA device with a mean follow-up of 5.8 ± 3.8 months. The primary safety end point (freedom from death, myocardial infarction, stroke, or emergency surgery) at 30 days was met in 28 patients, whereas 2 patients died of device-related complications. The primary efficacy end point (MR reduction of at least 1.0 grade or reduction of regurgitant orifice area by 0.1 cm(2) or regurgitant volume by 15 mL or regurgitant fraction by 10% compared with baseline) was obtained in 13 patients. No significant changes were noted in MR parameters, ventricular volumes, or QOL. Distance walked on 6 minutes testing at 6-month follow-up increased from 331 ± 167 m to 417 ± 132 m (P = .65). Compared with nonresponders, responders had a higher baseline regurgitant orifice area >0.2 cm(2) (P = .001) and less prior history of myocardial infarction (P = .02), coronary artery bypass surgery (P = .03), and ischemic MR (P = .04). CONCLUSIONS Overall, PTMA had mild impact on MR reduction, left ventricular remodeling, QOL, and exercise capacity. During follow-up, the risk/benefit ratio remained suboptimal.

Infarct size and left ventricular function in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-segment Elevation (PREPARE) trial: ancillary cardiovascular magnetic resonance study

Objectives The aim of the study was to evaluate whether primary percutaneous coronary intervention (PCI) with combined proximal embolic protection and thrombus aspiration results in smaller final infarct size and improved left ventricular function assessed by cardiovascular magnetic resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) patients compared with primary PCI alone. Background Primary PCI with the Proxis system improves immediate microvascular flow post-procedure as measured by ST-segment resolution, which could result in better outcomes. Methods The ancillary CMR study included 206 STEMI patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST-Elevation (PREPARE) trial. CMR imaging was assessed between 4 and 6 months after the index procedure. Results There were no significant differences in final infarct size (6.1 g/m2 vs 6.3 g/m2, p = 0.78) and left ventricular ejection fraction (50% vs 50%, p = 0.46) between both groups. Also, systolic wall thickening in the infarct area (44% vs 45%, p = 0.93) or the extent of transmural segments (8.3% of segments vs 8.3% of segments, p = 0.60) showed no significant differences. The incidence of major adverse cardiac and cerebral events at 6 months was similar in the Proxis and control group (8% vs 10%, respectively, p = 0.43). Conclusions Primary PCI with combined proximal embolic protection and thrombus aspiration in STEMI patients did not result in significant differences in final infarct size or left ventricular function at follow-up CMR. In addition, there was no difference in the incidence of major adverse cardiac and cerebral events at 6 months. Trial registration number ISRCTN71104460.

Feasibility and applicability of computer-assisted myocardial blush quantification after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction†

Objectives: The aim of the study was to evaluate whether the “Quantitative Blush Evaluator” (QuBE) score is associated with measures of myocardial reperfusion in patients with ST‐segment elevation myocardial infarction (STEMI) treated in two hospitals with 24/7 coronary intervention facilities. Background: QuBE is an open source computer program to quantify myocardial perfusion. Although QuBE has shown to be practical and feasible in the patients enrolled in the Thrombus Aspiration during Percutaneous Coronary Intervention in Acute Myocardial Infarction Study (TAPAS), QuBE has not yet been verified on reperfusion outcomes of primary percutaneous coronary intervention (PCI) patients treated in other catheterization laboratories. Methods: Core lab adjudicated angiographic outcomes and QuBE values were assessed on angiograms of patients who were enrolled in the PRoximal Embolic Protection in Acute myocardial infarction and Resolution of ST‐Elevation (PREPARE) trial. ST‐segment resolution immediately after PCI measured by continuous ST Holter monitoring was calculated by a blinded core lab. Results: The QuBE score could be assessed on 229 of the 284 angiograms (81%) and was significantly associated with visually assessed myocardial blush grade (P < 0.0001). Patients with improved postprocedural Thrombolysis in Myocardial Infarction‐graded flow, myocardial blush grade, ST‐segment resolution immediately after PCI, or a small infarct size measured by peak CK‐MB had a significant better QuBE score. Conclusions: QuBE is feasible and applicable at angiograms of patients with STEMI recorded at other catheterization laboratories and is associated with measures of myocardial reperfusion.

Computer-assisted quantification of myocardial reperfusion after primary percutaneous coronary intervention predicts functional and contrast-enhanced cardiovascular magnetic resonance outcomes in patients with ST-segment elevation myocardial infarction†‡

Objective. We investigated whether the Quantitative Blush Evaluator (QuBE) value predicts functional and contrast‐enhanced cardiovascular magnetic resonance (CMR) outcomes at 4–6 months after primary percutaneous coronary intervention (PCI) in patients with ST‐segment elevation myocardial infarction (STEMI). Background. QuBE is a computer‐assisted open source program to quantify myocardial reperfusion. Although a higher QuBE value is associated with improved myocardial reperfusion measures and lower 1‐year mortality, the association with intermediate functional parameters after STEMI has not yet been investigated. Methods. QuBE values were quantified retrospectively on angiograms of patients enrolled in the ancillary CMR study of the proximal embolic protection in acute myocardial infarction and resolution of ST‐elevation trial. QuBE en CMR outcomes were independently assessed by reviewers blinded to clinical data. Results. A higher QuBE value was significantly associated with a smaller left ventricular (LV) end‐diastolic and end‐systolic volume, a higher LV ejection fraction and systolic wall thickening in the infarct area, and a smaller final infarct size and extent of transmural segments (P ≤ 0.008). In a multivariable model, including age, gender, infarct location, time to treatment, history of myocardial infarction, and postprocedural thrombolysis in myocardial infarction flow grade, only the QuBE value and infarct location remained as independent predictors of LV ejection fraction (P = 0.018 for QuBE value). Conclusion. Higher QuBE values are independently associated with improved functional and contrast‐enhanced CMR outcomes including LV ejection fraction at 4–6 months after primary PCI and may therefore aid in identifying high‐risk patients who benefit most from adjunctive therapies sustaining myocardial function after PCI.

Excimer Laser Revascularization of Calcified Lesions

Calcified coronary and peripheral vessel stenosis are one of the leading causes of mortality and morbidity in US. Despite being a relatively common problem, vascular calcification has been underappreciated. Due to suboptimal procedural results in subsets of calcified vessels such as uncrossable chronic total occlusions, undilatable in-stent stenosis and calcified plaques, excimer laser coronary angioplasty is an attractive additional resource to deal with these challenging lesions.