Marino Labinaz

A Citywide Protocol for Primary PCI in ST-Segment Elevation Myocardial Infarction

BACKGROUND If primary percutaneous coronary intervention (PCI) is performed promptly, the procedure is superior to fibrinolysis in restoring flow to the infarct-related artery in patients with ST-segment elevation myocardial infarction. The benchmark for a timely PCI intervention has become a door-to-balloon time of less than 90 minutes. Whether regional strategies can be developed to achieve this goal is uncertain. METHODS We developed an integrated-metropolitan-area approach in which all patients with ST-segment elevation myocardial infarction were referred to a specialized center for primary PCI. We sought to determine whether there was a difference in door-to-balloon times between patients who were referred directly from the field by paramedics trained in the interpretation of electrocardiograms and patients who were referred by emergency department physicians. RESULTS Between May 1, 2005, and April 30, 2006, a total of 344 consecutive patients with ST-segment elevation myocardial infarction were referred for primary PCI: 135 directly from the field and 209 from emergency departments. Primary PCI was performed in 93.6% of patients. The median door-to-balloon time was shorter in patients referred from the field (69 minutes; interquartile range, 43 to 87) than in patients needing interhospital transfer (123 minutes; interquartile range, 101 to 153; P<0.001). Door-to-balloon times of less than 90 minutes were achieved in 79.7% of patients who were transferred from the field and in 11.9% of those transferred from emergency departments (P<0.001). CONCLUSIONS Guideline door-to-balloon-times were more often achieved when trained paramedics independently triaged and transported patients directly to a designated primary PCI center than when patients were referred from emergency departments.

Contrast-Induced Nephropathy and Long-Term Adverse Events: Cause and Effect?

BACKGROUND AND OBJECTIVES The relationship of contrast-induced nephropathy (CIN) to long-term adverse events (AEs) is controversial. Although an association with AEs has been previously reported, it is unclear whether CIN is causally related to these AEs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We obtained long-term (> or =1 yr) follow-up on 294 patients who participated in a randomized, double-blind comparison of two prevention strategies for CIN (iopamidol versus iodixanol). A difference in the incidence of AEs between patients who had developed CIN and those who had not was performed using a chi(2) test and Poisson regression analysis. A similar statistical approach was used for the differences in AEs between those who received iopamidol or iodixanol. Multiple definitions of CIN were used to strengthen and validate the results and conclusions. RESULTS The rate of long-term AEs was higher in individuals with CIN (all definitions of CIN). After adjustment for baseline comorbidities and risk factors, the adjusted incidence rate ratio for AEs was twice as high in those with CIN. Randomization to iopamidol reduced both the incidence of CIN and AEs. CONCLUSIONS The parallel decrease in the incidence of CIN and AEs in one arm of this randomized trial supports a causal role for CIN.

2-Year Follow-Up of Patients Undergoing Transcatheter Aortic Valve Implantation Using a Self-Expanding Valve Prosthesis

OBJECTIVES The purpose of this study was to evaluate the safety, device performance, and clinical outcome up to 2 years for patients undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND The role of TAVI in the treatment of calcific aortic stenosis evolves rapidly, but mid- and long-term results are scarce. METHODS We conducted a prospective, multicenter, single-arm study with symptomatic patients undergoing TAVI for treatment of severe aortic valve stenosis using the 18-F Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis. RESULTS In all, 126 patients (mean age 82 years, 42.9% male, mean logistic European System for Cardiac Operative Risk Evaluation score 23.4%) with severe aortic valve stenosis (mean gradient 46.8 mm Hg) underwent the TAVI procedure. Access was transfemoral in all but 2 cases with subclavian access. Retrospective risk stratification classified 54 patients as moderate surgical risk, 51 patients as high-risk operable, and 21 patients as high-risk inoperable. The overall technical success rate was 83.1%. Thirty-day all-cause mortality was 15.2%, without significant differences in the subgroups. At 2 years, all-cause mortality was 38.1%, with a significant difference between the moderate-risk group and the combined high-risk groups (27.8% vs. 45.8%, p = 0.04). This difference was mainly attributable to an increased risk of noncardiac mortality among patients constituting the high-risk groups. Hemodynamic results remained unchanged during follow-up (mean gradient: 8.5 ± 2.5 mm Hg at 30 days and 9.0 ± 3.4 mm Hg at 2 years). Functional class improved in 80% of patients and remained stable over time. There was no incidence of structural valve deterioration. CONCLUSIONS The TAVI procedure provides sustained clinical and hemodynamic benefits for as long as 2 years for patients with symptomatic severe aortic stenosis at increased risk for surgery.

Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Artery Disease

OBJECTIVES The purpose of this study was to test the hypothesis that 9p21 gene dosage determines the severity of coronary artery disease (CAD). BACKGROUND The 9p21 locus is the first common genetic variant to associate with risk of CAD and/or myocardial infarction in multiple studies. METHODS A cross-sectional study examined nondiabetic patients with CAD defined by coronary angiography to have at least 1 epicardial stenosis >50%. In all, 950 patients with early onset CAD (age 56.1 +/- 9.6 years) and an independent sample of 764 patients with late onset CAD (age 70.0 +/- 8.0 years) were enrolled from the cardiac catheterization laboratories at the University of Ottawa Heart Institute from April 15, 2006, to August 15, 2008, and genotyped for the single nucleotide polymorphism rs1333049 9p21 risk variant. Angiographers were blinded to genotype. The association between 9p21 risk genotype and the proportion of patients with 3-vessel disease, 1-vessel disease, left main trunk disease, and coronary artery bypass graft surgery was tested, as was its association with the modified Gensini and Duke coronary scoring indexes. RESULTS Among younger CAD cases, 3-vessel disease demonstrated a strong, direct association with 9p21 gene dosage (p = 4.26 x 10(-4)). Conversely, 1-vessel disease demonstrated a strong inverse association with increasing gene dosage (p = 2.41 x 10(-5)). In the replication sample, gene dosage also predicted 3-vessel disease (p = 6.51 x 10(-6)). Left main trunk disease and coronary artery bypass graft surgery demonstrated a direct strong association with gene dosage (p = 3.66 x 10(-4)) and (p = 2.42 x 10(-2)), respectively. Gene dosage demonstrated a strong, direct association with both the modified Gensini (p < 0.0001) and modified Duke (p = 3 x 10(-4)) coronary scores. Risk variant 9p21 did not associate with myocardial infarction once stratified for disease severity. CONCLUSIONS Gene dosage of the common risk variant 9p21 predicts the severity of coronary atheromatous burden.

Randomized, Blinded Trial Comparing Fondaparinux With Unfractionated Heparin in Patients Undergoing Contemporary Percutaneous Coronary Intervention Arixtra Study in Percutaneous Coronary Intervention: A Randomized Evaluation (ASPIRE) Pilot Trial

Background—Factor Xa plays a central role in the generation of thrombin, making it a novel target for treatment of arterial thrombosis. Fondaparinux is a synthetic factor Xa inhibitor that has been shown to be superior to standard therapies for the prevention of venous thrombosis. We performed a randomized trial to determine the safety and feasibility of fondaparinux in the percutaneous coronary intervention (PCI) setting. Methods and Results—A total of 350 patients undergoing elective or urgent PCI were randomized in a blinded manner to receive unfractionated heparin (UFH), 2.5 mg fondaparinux IV, or 5.0 mg fondaparinux IV. Randomization was stratified for planned or no planned use of glycoprotein (GP) IIb/IIIa antagonists. The primary safety outcome was total bleeding, which was a combination of major and minor bleeding events. The incidence of total bleeding was 7.7% in the UFH group and 6.4% in the combined fondaparinux groups (hazard ratio, 0.81; 95% confidence interval, 0.35 to 1.84; P=0.61). Bleeding was less common in the 2.5-mg fondaparinux group compared with the 5-mg fondaparinux group (3.4% versus 9.6%, P=0.06). The composite efficacy outcome of all-cause mortality, myocardial infarction, urgent revascularization, or need for a bailout GPIIb/IIIa antagonist was 6.0% in the UFH group and 6.0% in the fondaparinux group, with no significant difference in efficacy among the fondaparinux doses compared with UFH. Coagulation marker analysis at 6 and 12 hours after PCI demonstrated that fondaparinux was superior to UFH in inducing a sustained reduction in markers of thrombin generation, as measured by prothrombin fragment F1.2 (P=0.02). Conclusions—In this pilot study of patients undergoing contemporary PCI, factor Xa inhibition with the synthetic anticoagulant fondaparinux in doses of 2.5 and 5.0 mg was comparable to UFH for clinical safety and efficacy outcomes. These data form the basis for further evaluation of fondaparinux in arterial thrombosis.

Stenting versus thrombolysis in acute myocardial infarction trial (STAT)

OBJECTIVES We sought to directly compare primary stenting with accelerated tissue plasminogen activator (t-PA) in patients presenting with acute ST-elevation myocardial infarction (AMI). BACKGROUND Thrombolysis remains the standard therapy for AMI. However, at some institutions primary angioplasty is favored. Randomized trials have shown that primary angioplasty is equal or superior to thrombolysis, while recent studies demonstrate that stent implantation improves the results of primary angioplasty. METHODS Patients presenting with AMI were randomly assigned to primary stenting (n = 62) or accelerated t-PA (n = 61). The primary end point was the composite of death, reinfarction, stroke or repeat target vessel revascularization (TVR) for ischemia at six months. RESULTS The primary end point was significantly reduced in the stent group compared with the accelerated t-PA group, 24.2% versus 55.7% (p < 0.001). The event rates for other outcomes in the stent group versus the t-PA group were as follows: mortality: 4.8% versus 3.3% (p = 1.00); reinfarction: 6.5% versus 16.4% (p = 0.096); stroke: 1.6% versus 4.9% (p = 0.36); recurrent unstable ischemia: 9.7% versus 26.2% (p = 0.03) and repeat TVR for ischemia: 14.5% versus 49.2% (p < 0.001). The median length of the initial hospitalization was four days in the stent group and seven days in the t-PA group (p < 0.001). CONCLUSIONS Compared with accelerated t-PA, primary stenting reduces death, reinfarction, stroke or repeat TVR for ischemia. In centers where facilities and experienced interventionists are available, primary stenting offers an attractive alternative to thrombolysis.

Enhanced Efficacy of Eptifibatide Administration in Patients With Acute Coronary Syndrome Requiring In-Hospital Coronary Artery Bypass Grafting

Background—Patients with a recent episode of non–ST-segment elevation acute coronary syndrome before CABG have higher rates of operative morbidity and mortality than patients with stable coronary syndromes. The efficacy of administering eptifibatide to these patients undergoing in-hospital CABG is unknown. Methods and Results—The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomized 10 948 patients to receive either eptifibatide or placebo. There were 1558 study participants who underwent in-hospital CABG: 692 received placebo, and 866 received eptifibatide. The main substudy analysis end point was death or myocardial infarction (MI) rates at the 6-month follow-up. The 30-day death or MI rates were 30.8% and 26.1% for the placebo and eptifibatide groups, respectively (P =0.041). The benefit of eptifibatide administration persisted through 6-months of follow-up (32.7% versus 27.6% for placebo versus eptifibatide, respectively;P =0.029). There was a greater reduction in the 6-month death or MI rate for patients who received eptifibatide within 72 hours of CABG (33.6% versus 23.8%;P =0.002) compared with the >72-hour group (31.6% versus 32%;P =1.0). The incidence of major bleeding was 56.6% for placebo-treated patients versus 58.2% for eptifibatide-treated patients (P =0.7). Conclusions—Eptifibatide administration in patients undergoing in-hospital CABG with a recent episode of a non–ST-segment elevation acute coronary syndrome results in a significant reduction in death or MI that is evident at 7 days and persists through the 6-month follow-up without a significant increase in perioperative bleeding rates.

Safety and Effectiveness of Drug-Eluting and Bare-Metal Stents for Patients With Off- and On-Label Indications

OBJECTIVES Our main objective was to evaluate the longer-term safety and efficacy of drug-eluting stents (DES) in off-label indications as compared with bare-metal stents (BMS). BACKGROUND DES are frequently implanted in patients with off-label indications. However, the longer-term safety and effectiveness of DES among patients with off-label indications are not well understood. METHODS Propensity score matching analysis was performed in a population-based cohort that included 6,944 off-label and 9,126 on-label patients who received percutaneous coronary interventions (PCIs) in Ontario, Canada, between December 1, 2003, and March 31, 2006. Off-label indications were defined on the basis of clinical and procedural characteristics. RESULTS For patients with off-label indications, rates of repeat target vessel revascularization at 3 years were significantly lower among patients treated with DES compared with those treated with BMS (11.6% vs. 15.3%, p < 0.001). Myocardial infarction rates were not significantly different between patients treated with DES and BMS (p = 0.52). Mortality rates were significantly lower among off-label patients treated with DES compared with BMS at 3 years of follow-up (6.9% vs. 10.5%, p < 0.001). For patients with on-label indications, the use of DES was associated with significantly lower rates of target vessel revascularization, but composite rates of myocardial infarction or death were not significantly different from BMS. CONCLUSIONS For patients with off-label indications, DES implantation was associated with lower target vessel revascularization without an associated increase in longer-term risk of myocardial infarction or death compared with BMS.

Usefulness of mean platelet volume as a biomarker for long-term outcomes after percutaneous coronary intervention.

Larger size platelets have enhanced reactivity. The mean platelet volume (MPV) is a marker of platelet activation and is usually measured as part of blood testing. The aim of the present study was to investigate the utility of the MPV as a biomarker in prognosticating the long-term outcomes after percutaneous coronary intervention (PCI). The baseline MPV values from consecutive patients undergoing PCI were screened. Of the 1,432 patients, the composite primary end point of mortality or myocardial infarction at 1 year occurred in 80 (5.6%). The patients in the highest tertile (MPV >9.1 fL) had an increased frequency of the primary end point compared to those in the mid (8.1 to 9.1 fL) and lowest (<8.1 fL) tertiles (9.0%, 4.5%, and 3.5%, respectively; p <0.01). Logistic regression analysis demonstrated diabetes (odds ratio 2.44, 95% confidence interval 1.48 to 4.00) and highest tertile of MPV (odds ratio 2.42, 95% confidence interval 1.47 to 3.99) as the best predictors of adverse outcomes. In patients with acute coronary syndrome, the preprocedural MPV and troponin levels demonstrated a comparable predictive relation to the primary end point (receiver operator characteristics curve analysis, area under the curve 0.64, p = 0.01; and 0.63, p = 0.01, respectively). In conclusion, an elevated MPV was a strong independent predictor of long-term outcomes after PCI. The preprocedural MPV had prognostic value similar to that of troponin in patients with acute coronary syndrome. These findings could be of importance in the clinical evaluation of patients before PCI and the design of future studies assessing antiplatelet therapies.

Reduction in Mortality as a Result of Direct Transport From the Field to a Receiving Center for Primary Percutaneous Coronary Intervention

OBJECTIVES This study sought to determine whether mortality complicating ST-segment elevation myocardial infarction (STEMI) was impacted by the design of transport systems. BACKGROUND It is recommended that regions develop systems to facilitate rapid transfer of STEMI patients to centers equipped to perform primary percutaneous coronary intervention (PCI), yet the impact on mortality from the design of such systems remains unknown. METHODS Within the framework of a citywide system where all STEMI patients are referred for primary PCI, we compared patients referred directly from the field to a PCI center to patients transported beforehand from the field to a non-PCI-capable hospital. The primary outcome was all-cause mortality at 180 days. RESULTS A total of 1,389 consecutive patients with STEMI were assessed by the emergency medical services (EMS) and referred for primary PCI: 822 (59.2%) were referred directly from the field to a PCI center, and 567 (40.8%) were transported to a non-PCI-capable hospital first. Death at 180 days occurred in 5.0% of patients transferred directly from the field, and in 11.5% of patients transported from the field to a non-PCI-capable hospital (p < 0.0001. After adjusting for baseline characteristics in a multivariable logistic regression model, mortality remained lower among patients referred directly from the field to the PCI center (odds ratio: 0.52, 95% confidence interval: 0.31 to 0.88, p = 0.01). Similar results were obtained by using propensity score methods for adjustment. CONCLUSIONS A STEMI system allowing EMS to transport patients directly to a primary PCI center was associated with a significant reduction in mortality. Our results support the concept of STEMI systems that include pre-hospital referral by EMS.