Detlef G. Mathey

RANDOMISED TRIAL OF INTRAVENOUS RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR VERSUS INTRAVENOUS STREPTOKINASE IN ACUTE MYOCARDIAL INFARCTION: Report from the European Cooperative Study Group for Recombinant Tissue-type Plasminogen Activator

In a single-blind randomised trial in patients with acute myocardial infarction of less than 6 h duration, the frequency of coronary patency was found to be higher after intravenous administration of recombinant human tissue-type plasminogen activator (rt-PA) than after intravenous streptokinase. 64 patients were allocated to 0.75 mg rt-PA/kg over 90 min, and the infarct-related coronary artery was patent in 70% of 61 assessable coronary angiograms taken 75-90 min after the start of infusion; 65 patients were allocated to 1 500 000 IU streptokinase over 60 min, and the infarct-related vessel was patent in 55% of 62 assessable angiograms. The 95% confidence interval of the differences ranges from +/- 30 to -2% (p = 0.054). Bleeding episodes and other complications were less common in the rt-PA patients than in the streptokinase group. Hospital mortality was identical in the 2 treatment groups. At the end of the rt-PA infusion the circulating fibrinogen level was 61 +/- 35% of the starting value, as measured by a coagulation-rate assay, and 69 +/- 25% as measured by sodium sulphite precipitation. After streptokinase infusion, corresponding fibrinogen levels were 12 +/- 18% and 20 +/- 11%. In the rt-PA group only 4.5% of the fibrinogen was measured as incoagulable fibrinogen degradation products, compared with 30% in the streptokinase group. Activation of the systemic fibrinolytic system was far less pronounced with rt-PA than with streptokinase.

Clinical Outcome 2 Years After Intracoronary Administration of Bone Marrow–Derived Progenitor Cells in Acute Myocardial Infarction

Background—The aim of this study was to investigate the clinical outcome 2 years after intracoronary administration of autologous progenitor cells in patients with acute myocardial infarction (AMI). Methods and Results—Using a double-blind, placebo-controlled, multicenter trial design, we randomized 204 patients with successfully reperfused AMI to receive intracoronary infusion of bone marrow–derived progenitor cells (BMC) or placebo medium into the infarct artery 3 to 7 days after successful infarct reperfusion therapy. At 2 years, the cumulative end point of death, myocardial infarction, or necessity for revascularization was significantly reduced in the BMC group compared with placebo (hazard ratio, 0.58; 95% CI, 0.36 to 0.94; P=0.025). Likewise, the combined end point death and recurrence of myocardial infarction and rehospitalization for heart failure, reflecting progression toward heart failure, was significantly reduced in the BMC group (hazard ratio, 0.26; 95% CI, 0.085 to 0.77; P=0.015). Intracoronary administration of BMC remained a significant predictor of a favorable clinical outcome by Cox regression analysis when adjusted for classical predictors of poor outcome after AMI. There was no evidence of increased restenosis or atherosclerotic disease progression after BMC therapy nor any evidence of increased ventricular arrhythmias or neoplasms. In addition, regional left ventricular contractility of infarcted segments, as assessed by MRI in a subgroup of patients at 2-year follow-up, was significantly higher in the BMC group compared with the placebo group (P<0.001). Conclusions—Intracoronary administration of BMC is associated with a significant reduction of the occurrence of major adverse cardiovascular events maintained for 2 years after AMI. Moreover, functional improvements after BMC therapy may persist for at least 2 years. Larger studies focusing on clinical event rates are warranted to confirm the effects of BMC administration on mortality and progression of heart failure in patients with AMIs. Clinical Trial Registration—clinicaltrials.gov. Identifier: NCT00279175.

DOUBLE-BLIND RANDOMISED TRIAL OF INTRAVENOUS TISSUE-TYPE PLASMINOGEN ACTIVATOR VERSUS PLACEBO IN ACUTE MYOCARDIAL INFARCTION

In a double-blind randomised trial 129 patients with first myocardial infarction of less than 6 h duration were allocated to treatment with human recombinant tissue-type plasminogen activator (rt-PA) given intravenously over 90 min, or to placebo infusion. Coronary angiography at the end of this infusion showed that the infarct-related vessel was patent in 61% of 62 assessable coronary angiograms in the rt-PA-treated group compared with 21% in the control group. Treatment with rt-PA was not accompanied by any major complications. In the rt-PA group the circulating fibrinogen level at the end of the catheterisation was 52 +/- 29% (mean +/- SD) of the starting value.

Impact of compensatory enlargement of atherosclerotic coronary arteries on angiographic assessment of coronary artery disease.

To determine whether compensatory enlargement of atherosclerotic coronary arteries occurs and to what degree it affects the angiographic assessment of coronary artery disease, we performed postmortem coronary angiography of 30 human hearts with suspected coronary artery disease and studied 70 histologic cross sections of the proximal left anterior descending artery and proximal right coronary artery. Angiographic and morphometric analyses of 50 stenoses in proximal and middle sections of the left anterior descending artery, right coronary artery, and left circumflex artery were performed. The control group of 10 human hearts without suspected coronary artery disease was evaluated in the same way. For this purpose, coronary arteries were filled with a methylmethacrylic radiopaque resin at a pressure of 100 mm Hg and closely embedded in a methylmethacrylic resin by use of which shrinkage and mechanical artifacts could be avoided. The area circumscribed by the internal elastic lamina was taken as a measure of the area of the arterial lumen if no plaque had been present. The angiographic and corresponding morphometric degree of stenosis was assessed. A significant correlation (r = 0.85, p less than or equal to 0.0001) was found between the internal elastic lamina area and the area of the plaque (lesion area), suggesting that coronary arteries may enlarge as lesion area increases. With the morphometric degree of stenosis, the expected anatomic diminution of the coronary artery was abolished (r = 0.79, p less than or equal to 0.0001), indicating compensatory enlargement in atherosclerotic segments. Accordingly, the degree of stenosis assessed from in vitro angiograms was underestimated. Compensatory coronary enlargement of the stenotic segment was the main reason for angiographic underestimation. The underestimation factor of up to 3.50 for very mild stenoses decreased to 1.37 at an angiographic degree of 50% area stenosis and 30% diameter stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Supported High-Risk Percutaneous Coronary Intervention With the Impella 2.5 Device: The Europella Registry

OBJECTIVES This retrospective multicenter registry evaluated the safety and feasibility of left ventricular (LV) support with the Impella 2.5 (Abiomed Europe GmbH, Aachen, Germany) during high-risk percutaneous coronary intervention (PCI). BACKGROUND Patients with complex or high-risk coronary lesions, such as last remaining vessel or left main lesions, are increasingly being treated with PCI. Because periprocedural hemodynamic compromise and complications might occur rapidly, many of these high-risk procedures are being performed with mechanical cardiac assistance, particularly in patients with poor LV function. The Impella 2.5, a percutaneous implantable LV assist device, might be a superior alternative to the traditionally used intra-aortic balloon pump. METHODS The Europella registry included 144 consecutive patients who underwent a high-risk PCI. Safety and feasibility end points included incidence of 30-day adverse events and successful device function. RESULTS Patients were older (62% >70 years of age), 54% had an LV ejection fraction < or = 30%, and the prevalence of comorbid conditions was high. Mean European System for Cardiac Operative Risk Evaluation score was 8.2 (SD 3.4), and 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function in 53%, 17%, 81%, and 35% of the cases, respectively. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. CONCLUSIONS This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI.

Focal ischemia of the brain after neuroprotected carotid artery stenting

OBJECTIVES This study sought to assess the incidence of cerebral ischemia in nonselected patients undergoing neuroprotected carotid angioplasty and stenting (CAS) without preceding multiple-vessel diagnostic angiography. BACKGROUND Protection devices to prevent distal embolization during CAS are presently under clinical investigation. Diffusion-weighted magnetic resonance imaging (MRI) visualizes recent ischemia of the brain and may aid in assessing the efficacy of protection devices. METHODS Elective CAS was performed in 42 consecutive patients (15 female, 27 male; mean age, 67 +/- 9 years) using six different types of cerebral protection systems. All patients underwent MRI of the brain before and after a total of 44 interventions. RESULTS Placement and retrieval of the devices and stent deployment was achieved in all procedures. New ischemic foci were seen on postinterventional MRI in 10 cases (22.7%). One patient had sustained a major stroke, whereas no adverse neurological sequelae were associated with the other nine procedures. In the latter, one to three foci (maximum area 43.0 mm(2)) were detected in cerebral regions subtended by the ipsilateral carotid artery in eight cases and by the contralateral carotid artery in one case. In the stroke patient, 12 ischemic foci (maximum area 84.5 mm(2)) were exclusively located in the contralateral hemisphere. Follow-up MRI at 4.1 months (median, n = 7) identified residuals of cerebral ischemia only in this patient. CONCLUSIONS Neuroprotected CAS is associated in about 25% of cases with predominantly silent cerebral ischemia. Our findings suggest manipulation of endoluminal equipment in the supraaortic vessels to be a major risk factor for cerebral embolism during neuroprotected CAS.

Scintigraphic evidence of the “No reflow” phenomenon in human beings after coronary thrombolysis

To assess whether the absence of new thallium-201 uptake after successful intracoronary thrombolysis reflects a disturbance of myocardial cell function or lack of capillary reperfusion, dual isotope scintigraphic studies with thallium-201 and technetium-99m micro-albumin aggregates were performed in 16 patients with acute anterior myocardial infarction. Intracoronary thallium-201 and technetium-99m scintigraphy performed before intracoronary thrombolysis in 12 of the 16 patients resulted in identical thallium-201 and technetium-99m defect sizes. Immediately after intracoronary thrombolysis, thallium-201 and technetium-99m scintigraphy was repeated in 11 of the 12 patients. In 4 of the 11, the initial thallium and technetium scintigraphic defects were significantly reduced, and in 6 of the 11, they were only slightly reduced; there was no difference in the size of the residual defect as assessed with both radionuclides in all 10 of the 11 patients. In the eleventh patient, there was a significant reduction of the initial technetium-99m scintigraphic defect but no change in the size of the thallium-201 defect. In four other patients, scintigrams were obtained only after intracoronary thrombolysis; these revealed no difference in thallium-201 and technetium-99m defect size. In seven of eight patients restudied 2 to 4 weeks after intracoronary thrombolysis, thallium-201 and technetium-99m defect sizes were identical with those immediately after intracoronary thrombolysis; in the eighth patient there was no difference in thallium-201 and technetium-99m defect size, although such a difference had been present immediately after intracoronary thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Time from onset of symptoms to thrombolytic therapy: a major determinant of myocardial salvage in patients with acute transmural infarction.

To determine whether myocardial salvage after successful intracoronary or intravenous thrombolysis is time dependent, the relation between left ventricular wall motion and the time to treatment was studied in 69 patients admitted less than 3 hours after onset of acute transmural myocardial infarction (42 patients with reperfusion by intracoronary streptokinase, 27 by intravenous urokinase). A similar significant relation between the time to treatment and the severity of regional hypokinesia at follow-up was found in the intracoronary and intravenous groups. To better define this relation, particularly during the early phase of infarction, the groups were combined. In patients in whom thrombolytic treatment was initiated within 2 hours after symptom onset, wall motion at follow-up was within 2 standard deviations of the normal mean in 82% (14 of 17 patients). If treatment was started 2 to 5 hours after symptom onset, the probability of improved wall motion decreased to 46% (24 of 52 patients, p less than 0.025). The time/wall motion relation appeared to be independent of infarct location, angiographically visible collateral vessels and the presence of subtotal coronary artery occlusion. The severity of hypokinesia at follow-up study correlated with the magnitude of peak serum creatine kinase (r = -0.71), indicating that thrombolytic therapy initiated within 2 hours after the onset of symptoms improves regional left ventricular function and reduces infarct size more than later therapy does.

Influence of treatment modality on angiographic outcome after coronary stenting in diabetic patients: a controlled study

OBJECTIVES This retrospective study was designed to determine the six-month angiographic outcome after stenting of native coronary arteries in insulin-treated (ITDM) and non-ITDM patients with diabetes mellitus (DM) and compare the results with those in non-DM patients. BACKGROUND The influence of the treatment modality for DM on restenosis in patients undergoing coronary artery stenting has not been elucidated sufficiently. METHODS A total of 1,439 (70%) of 2,061 patients underwent repeated angiography within six months of coronary stenting. The ITDM and non-ITDM (oral hypoglycemic drugs or diet) were documented in 48 (3.3%) and 177 patients (12.3%), respectively, leaving 1,214 non-DM patients. RESULTS Baseline reference vessel diameter tended to be smaller in ITDM patients (mean, 2.73 mm) than in non-DM and non-ITDM patients (2.88 mm and 2.85 mm, respectively). However, percent diameter stenosis was not different. The median number of stents deployed was 1; median stent length was 15 mm. Statistically significant differences were present after stenting for the means of minimal lumen diameter (MLD) and acute gain between ITDM patients (MLD: 2.67 mm, acute gain: 1.98 mm) and non-DM patients (MLD: 2.81 mm, acute gain: 2.16 mm). At follow-up, percent diameter stenosis, late lumen loss and loss index were significantly higher in both non-ITDM lesions (42%, 1.14 mm and 0.56, respectively) and ITDM lesions (48%, 1.26 mm and 0.65, respectively) than in non-DM lesions (35%, 0.96 mm and 0.45, respectively). The corresponding differences between non-ITDM and ITDM lesions did not reach statistical significance. Restenosis rates in non-DM, non-ITDM and ITDM lesions were 23.8%, 32.8% (p = 0.013 vs. non-DM) and 39.6% (p = 0.02 vs. non-DM, p = 0.477 vs. non-ITDM), respectively. CONCLUSIONS This study showed that compared with stenting in non-DM patients, stenting of native coronary arteries in DM patients is associated with significantly increased lumen renarrowing, regardless of the treatment modality for DM.

Intracoronary infusion of bone marrow-derived mononuclear cells abrogates adverse left ventricular remodelling post-acute myocardial infarction: insights from the reinfusion of enriched progenitor cells and infarct remodelling in acute myocardial infarction (REPAIR-AMI) trial

Depressed left ventricular ejection fraction (LVEF) despite successful reperfusion therapy is the single most powerful predictor of progressive LV enlargement after acute myocardial infarction (AMI) and independently determines adverse outcome in these patients.