Francois Schiele

Randomized Study to Assess the Effectiveness of Slow- and Moderate-Release Polymer-Based Paclitaxel-Eluting Stents for Coronary Artery Lesions

Background—Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient populations. Methods and Results—We conducted a randomized, double-blind trial of 536 patients at 38 medical centers evaluating slow-release (SR) and moderate-release (MR) formulations of a polymer-based paclitaxel-eluting stent (TAXUS) for revascularization of single, primary lesions in native coronary arteries. Cohort I compared TAXUS-SR with control stents, and Cohort II compared TAXUS-MR with a second control group. The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound. Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events, a composite of cardiac death, myocardial infarction, and repeat revascularization. At 6 months, percent net volume obstruction within the stent was significantly lower for TAXUS stents (7.9% SR and 7.8% MR) than for respective controls (23.2% and 20.5%; P <0.0001 for both). This corresponded with a reduction in angiographic restenosis from 17.9% to 2.3% in the SR cohort (P <0.0001) and from 20.2% to 4.7% in the MR cohort (P =0.0002). The incidence of major adverse cardiac events at 12 months was significantly lower (P =0.0192) in the TAXUS-SR (10.9%) and TAXUS-MR (9.9%) groups than in controls (22.0% and 21.4%, respectively), predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients. Conclusions—Compared with a bare metal stent, paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions.

False lumen patency as a predictor of late outcome in aortic dissection

Aortic dissection (AD) is a disease with a high-risk of mortality. Late deaths are often related to complications in nonoperated aortic segments. Between 1984 and 1996, we retrospectively analyzed the data of 109 patients with acute AD (81 men and 28 women; average age 61 +/- 14 years). All imaging examinations were reviewed, and a magnetic resonance imaging examination was performed at the time of the study. Aortic diameters were measured on each aortic segment. Predictive factors of mortality were determined by Coxs proportional hazard model, in univariate and multivariate analyses, using BMDP statistical software. Follow-up was an average of 44 +/- 46 months (range 24 to 164). Actuarial survival rates were 52%, 46%, and 37% at 1, 5, and 10 years, respectively, for type A AD versus 76%, 72%, and 46% for type B AD. Predictors of late mortality were age >70 years and postoperative false lumen patency of the thoracic descending aorta (RR 3.4, 95% confidence intervals 1.20 to 9.8). Descending aorta diameter was larger when false lumen was patent (31 vs 44 mm; p = 0.02) in type A AD. Furthermore, patency was less frequent in operated type A AD when surgery had been extended to the aortic arch. Thus, patency of descending aorta false lumen is responsible for progressive aortic dilation. In type A AD, open distal repair makes it possible to check the aortic arch and replace it when necessary, decreases the false lumen patency rate, and improves late survival.

Association of Changes in Clinical Characteristics and Management With Improvement in Survival Among Patients With ST-Elevation Myocardial Infarction

CONTEXT The contemporary decline in mortality reported in patients with ST-segment elevation myocardial infarction (STEMI) has been attributed mainly to improved use of reperfusion therapy. OBJECTIVE To determine potential factors-beyond reperfusion therapy-associated with improved survival in patients with STEMI over a 15-year period. DESIGN, SETTING, AND PATIENTS Four 1-month French nationwide registries, conducted 5 years apart (between 1995, 2000, 2005, 2010), including a total of 6707 STEMI patients admitted to intensive care or coronary care units. MAIN OUTCOME MEASURES Changes over time in crude 30-day mortality, and mortality standardized to the 2010 population characteristics. RESULTS Mean (SD) age decreased from 66.2 (14.0) to 63.3 (14.5) years, with a concomitant decline in history of cardiovascular events and comorbidities. The proportion of younger patients increased, particularly in women younger than 60 years (from 11.8% to 25.5%), in whom prevalence of current smoking (37.3% to 73.1%) and obesity (17.6% to 27.1%) increased. Time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units. Reperfusion therapy increased from 49.4% to 74.7%, driven by primary percutaneous coronary intervention (11.9% to 60.8%). Early use of recommended medications increased, particularly low-molecular-weight heparins and statins. Crude 30-day mortality decreased from 13.7% (95% CI, 12.0-15.4) to 4.4% (95% CI, 3.5-5.4), whereas standardized mortality decreased from 11.3% (95% CI, 9.5-13.2) to 4.4% (95% CI, 3.5-5.4). Multivariable analysis showed a consistent reduction in mortality from 1995 to 2010 after controlling for clinical characteristics in addition to the initial population risk score and use of reperfusion therapy, with odds mortality ratios of 0.39 (95%, 0.29-0.53, P <.001) in 2010 compared with 1995. CONCLUSION In France, the overall rate of cardiovascular mortality among patients with STEMI decreased from 1995 to 2010, accompanied by an increase in the proportion of women younger than 60 years with STEMI, changes in other population characteristics, and greater use of reperfusion therapy and recommended medications.

Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate: a multicenter, randomized study comparing two strategies—with and without intravascular ultrasound guidance

OBJECTIVES We aimed to investigate the impact of intravascular ultrasound (IVUS)-guided stent implantation on the 6-month restenosis rate, which has not yet been fully established in randomized trials. BACKGROUND The 6-month angiographic restenosis rate was compared in patients with symptomatic ischemic heart disease who were randomly allocated to angioplasty and stent deployment, with versus without IVUS guidance. METHODS After successful stent implantation, patients were randomized into two groups: Group A had no further dilation, and Group B had additional balloon dilation until achievement of IVUS criterion for stent expansion. The study group consisted of 164 patients, assuming a 50% reduction of the restenosis rate in Group B (15% vs. 30%) (alpha = 10%, beta = 20%). RESULTS We enrolled 155 patients. Overdilation was carried out in 31 (39%) of 79 Group B patients, with the IVUS criterion being achieved in 63 (80%) of 79. No significant difference was observed in the minimal luminal diameter (MLD), but the stent lumen cross-sectional area (CSA) was significantly larger in Group B (mean +/- SD) (7.16 +/- 2.48 vs. 7.95 +/- 2.21 mm2, p = 0.04). At 6 months, there was no significant difference in the restenosis rate, (28.8% [21 of 73] in Group A vs. 22.5% [16 of 71] in Group B, p = 0.25), but according to the observed difference in the restenosis rate, the power of the study was only 40%. The difference in MLD was also nonsignificant (1.60 +/- 0.65 mm in Group A vs. 1.70 +/- 0.64 mm in Group B, p = 0.20), whereas the lumen CSA was 20% larger in the IVUS-guided group (4.47 +/- 2.59 vs. 5.36 +/- 2.81 mm2, p = 0.03). Lumen CSA was the only predictor of restenosis by multivariate logistic regression analysis. CONCLUSIONS A nonsignificant 6.3% absolute reduction in the restenosis rate and a nonsignificant difference in MLD were observed in this study. Nonetheless, we still cannot rule out a beneficial effect of IVUS guidance, although this may have gone undetected owing to a lack of statistical power. A significant increase was observed in immediate and 6-month lumen size, as detected by IVUS, indicating that ultrasound guidance in stent deployment may be beneficial.

Comparative Efficacy of a Two-Hour Regimen of Streptokinase Versus Alteplase in Acute Massive Pulmonary Embolism: Immediate Clinical and Hemodynamic Outcome and One-Year Follow-Up

OBJECTIVES This study sought to compare the efficacy of 2-h regimens of alteplase and streptokinase in acute massive pulmonary embolism. The primary end point was immediate hemodynamic improvement, and secondary end points included early clinical efficacy and safety, as well as 1-year clinical outcome. BACKGROUND Several thrombolytic regimens have been compared for the past 10 years in randomized studies, showing that 2-h infusion regimens of alteplase or urokinase lead to faster hemodynamic improvement than former 12- to 24-h administration protocols in acute massive pulmonary embolism. Many trials have focused on immediate hemodynamic and angiographic outcomes, but none has addressed long-term follow-up after thrombolysis. METHODS Sixty-six patients with acute massive pulmonary embolism (Miller score > 17 and mean pulmonary artery pressure >20 mm Hg) were randomly assigned to receive either a 100-mg 2-h infusion of alteplase (n = 23) or 1.5 million IU of streptokinase over 2 h (n = 43). In both groups, heparin infusion was started at the end of thrombolytic infusion and adapted thereafter. Total pulmonary resistance was monitored over a 12-h period. Pulmonary vascular obstruction was assessed 36 to 48 h after thrombolytic therapy. One-year follow-up information included death, cause of death, recurrent pulmonary embolism, chronic thromboembolic pulmonary hypertension, stroke and bleeding. RESULTS Both groups had similar baseline angiographic and hemodynamic characteristics of severity, with maintained cardiac output in 64 (97%) of 66 patients. The results (mean +/- SD) demonstrated that despite a faster total pulmonary resistance improvement observed at 1 h in the alteplase group compared with the streptokinase group (33+/-16% vs. 19 16%, p = 0.006), a similar hemodynamic efficacy was obtained at 2 h when both thrombolytic regimens were completed (38+/-18% vs. 31+/-19%). There was no significant difference in either pulmonary vascular obstruction at 36 to 48 h or bleeding complication rates. One-year event-free survival was similar in both groups, as most events were related to concomitant diseases. CONCLUSIONS These results suggest that a 2-h regimen of streptokinase can be routinely used in patients with massive pulmonary embolism and maintained cardiac output without obviously compromising efficacy or safety.

Peristent Remodeling and Neointimal Suppression 2 Years After Polymer-Based, Paclitaxel-Eluting Stent Implantation: Insights From Serial Intravascular Ultrasound Analysis in the TAXUS II Study

Background— The purpose of this study was to evaluate long-term vascular responses as long as 2 years after implantation of polymer-based, paclitaxel-eluting stents in contrast to uncoated stents. Methods and Results— TAXUS II is a randomized, double-blind trial comparing slow-release (SR) and moderate-release (MR) TAXUS stents with bare-metal control stents (BMSs). One hundred sixty-one event-free patients (SR, 43; MR, 41; and BMS, 77) underwent serial intravascular ultrasound (IVUS) analysis after the procedure and at 6 months and 2 years. At 2 years, neointimal responses continued to be significantly suppressed in the SR and MR groups when compared with the BMS group (BMS, 1.49±1.12 mm2; SR, 0.94±0.76 mm2 [P=0.004]; and MR, 1.06±0.90 mm2 [P=0.02]). Between 6 months and 2 years, the BMS group showed compaction of the neointima (&Dgr;, −0.22±1.05 mm2 [P=0.08]). In contrast, both the SR and MR groups exhibited an increase (&Dgr; SR, 0.30±0.76 mm2 (P=0.01); MR, 0.41±0.94 mm2 [P=0.009]). Between 6 months and 2 years, the initial increase in plaque outside the stent regressed in the BMS and SR groups to levels comparable to those after the procedure, whereas expansive remodeling partially regressed in the MR group (&Dgr; between after the procedure and 2 years BMS, −0.34±1.28 mm2 [P=0.05]; SR, −0.02±1.40 mm2 [P=0.93]; MR, 0.32±1.56 mm2 [P=0.27]). Conclusions— The 2-year follow-up demonstrates that neointimal suppression was dose independent and that this effect was still sustained at 2 years. However, the increase in area outside the stent seen at 6 months regressed to different extents in a dose-dependent manner at 2 years.

The double-balloon and Inoue techniques in percutaneous mitral valvuloplasty: Comparative results in a series of 232 cases

Immediate hemodynamic results of percutaneous mitral valvuloplasty were compared in two consecutive series of unselected patients from the same institution undergoing valvuloplasty with the double-balloon (161 patients) or the Inoue balloon (71 patients) technique. Before valvuloplasty, the patient series were comparable with regard to average age, gender repartition and most clinical, electrocardiographic, X-ray and hemodynamic variables. Poor anatomic forms of mitral stenosis were equally distributed in both series (41% vs. 45%, p = NS). The magnitude of mitral valve area increase and of mean mitral gradient decrease during percutaneous mitral valvuloplasty did not differ significantly in the Inoue balloon and double-balloon series (mean +/- SEM 1.1 +/- 0.2 to 1.95 +/- 0.5 and 1.0 +/- 0.2 to 1.97 +/- 0.5 cm2, respectively, for mitral valve area and 12 +/- 3 to 5 +/- 2 and 13 +/- 4 to 5 +/- 2 mm Hg, respectively, for mean mitral gradient). Four cases of 3+ mitral regurgitation occurred in the Inoue balloon series and 7 in the double-balloon series (p = NS). A good immediate result--defined as mitral valve area greater than or equal to 1.5 cm2 with greater than or equal to 25% in mitral valve area gain and mitral regurgitation less than 2+ at the end of the procedure--was observed in 78% of patients in both series. Three cases of tamponade due to chamber perforation and 14 cases of transient air embolism in the right coronary system due to balloon rupture were observed in the double-balloon series.(ABSTRACT TRUNCATED AT 250 WORDS)

In-hospital and long-term outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy

Background From a registry of 249 confirmed pulmonary embolism (PE) patients submitted to thrombolytic therapy (TT), we analysed predictors of in-hospital course and long-term mortality. Methods and results The combined clinical end point of in-hospital course associated death, recurrent PE, repeat thrombolysis, surgical embolectomy or bleeding complications. The long-term follow-up included analysis of survival, and occurrence of PE-related events, defined as recurrent deep vein thrombosis, recurrent PE, occurrence of congestive heart failure or change of New York Heart Association functional class to class III or IV in patients who survived the acute phase. In-hospital clinical course was uneventful in 165 (66.3%) patients. Initial right ventricular (RV) dysfunction was reversible in 80% within 48h following TT. Initial pulmonary vascular obstruction >70% (RR=5.3 [2.1; 13.6]); haemodynamic instability at presentation (RR=2.6 [1.1; 6]); persistence of septal paradoxical motion after TT (RR=5.9 [1.4; 25.9]); and insertion of intracaval filter (RR=3.7 [1.4; 9.4]) were independent predictors of poor in-hospital course. Mean follow-up was 5.3±2.6 years. Of the 227 patients alive after the hospital stay, the probability of survival was 92% at 1 year, 79% at 3 years and 56% at 10 years. Multivariate predictors of long-term mortality were age >75 years (RR=2.73 [2.18; 3.21]; P =0.0002), persistence of vascular pulmonary obstruction >30% after thrombolytic treatment (RR=2.22 [1.69; 2.74]; P =0.003), and cancer (RR=2.03 [1.40; 2.65]; P =0.04). Conclusion The recovery of RV function should be considered as a marker of thrombolysis efficacy, while residual pulmonary vascular obstruction and cancer are independent predictors of long-term mortality. These results advocate the identification of high-risk patients by means of systematic lung-scan and echocardiography pre- and post-thrombolysis, and raise the question of the need for thromboendarterectomy in patients with residual pulmonary vascular obstruction.

Improved outcome of cardiogenic shock at the acute stage of myocardial infarction: a report from the USIK 1995, USIC 2000, and FAST-MI French Nationwide Registries

AIM The historical evolution of incidence and outcome of cardiogenic shock (CS) in acute myocardial infarction (AMI) patients is debated. This study compared outcomes in AMI patients from 1995 to 2005, according to the presence of CS. METHOD AND RESULTS Three nationwide French registries were conducted 5 years apart, using a similar methodology in consecutive patients admitted over a 1-month period. All 7531 AMI patients presenting ≤48 h of symptom onset were included. The evolution of mortality was compared in the 486 patients with CS vs. those without CS. The incidence of CS tended to decrease over time (6.9% in 1995; 5.7% in 2005, P = 0.07). Thirty-day mortality was considerably higher in CS patients (60.9 vs. 5.2%). Over the 10-year period, mortality decreased for both patients with (70-51%, P = 0.003) and without CS (9-4%, P < 0.001). In CS patients, the use of percutaneous coronary intervention (PCI) increased from 20 to 50% (P < 0.001). Time period was an independent predictor of early mortality in CS patients (OR for death, 2005 vs. 1995 = 0.45; 95% CI: 0.27-0.75, P = 0.005), along with age, diabetes, and smoking status. When added to the multivariate model, PCI was associated with decreased mortality (OR = 0.38; 95% CI: 0.24-0.58, P < 0.001). In propensity-score-matched cohorts, CS patients with PCI had a significantly higher survival. CONCLUSIONS Cardiogenic shock remains a clinical concern, although early mortality has decreased. Improved survival is concomitant with a broader use of PCI and recommended medications at the acute stage. Beyond the acute stage, however, 1-year survival has remained unchanged.

Reperfusion strategy in Europe: temporal trends in performance measures for reperfusion therapy in ST-elevation myocardial infarction

AIMS The rate and type of reperfusion, as well as time delays to reperfusion are directly associated with mortality and are established as performance measures (PMs) in the treatment of ST elevation myocardial infarction (STEMI). To date, little information exists about PMs for reperfusion in clinical practice in Europe and their temporal changes. METHODS AND RESULTS Using the Euro Heart Survey ACS-III data set (2 years of inclusions between 2006 and 2008, 138 centres in 21 countries), we selected patients with STEMI eligible for reperfusion therapy. Recorded variables corresponded to the CARDS data set. The rate and type of reperfusion, as well as door to needle and door to artery times were assessed and compared between periods. Timely reperfusion was defined as a door to needle time < 30 min, or a door to artery time < 90 min. We assessed changes in PMs for reperfusion over the 2 years of recruitment. Among 19 205 patients included in the registry, 7655 had STEMI, and 6481 were admitted within the first 12 h and eligible for reperfusion. The rate of patients who underwent reperfusion increased from 77.2 to 81.3%, with an increase in the use of primary percutaneous coronary intervention (P-PCI). The door to needle and door to artery times decreased significantly during the study period, from 20 to 15 min (P = 0.0011) and from 60 to 45 min (P < 0.0001) respectively. As a result, the number of eligible patients receiving reperfusion therapy in a timely manner increased from 53.1 to 63.5% (P < 0.0001). In parallel, over the 2-year period, in-hospital mortality decreased from 8.1 to 6.6% (P = 0.047). CONCLUSION In centres participating in the Euro Heart Survey ACS III, PMs for reperfusion in STEMI improved significantly between 2006 and 2008, with greater use of PCI. Similarly, the rate of patients reperfused in a timely manner also increased, with a significant reduction in door to needle and door to artery times.