Bas L. van der Hoeven

Late stent malapposition risk is higher after drug-eluting stent compared with bare-metal stent implantation and associates with late stent thrombosis.

AIMS Late stent malapposition (LSM) may be acquired (LASM) or persistent. LSM may play a role in patients who develop late stent thrombosis (ST). Our objective was to compare the risk of LASM in bare metal stents (BMS) with drug-eluting stents (DES) and to investigate the possible association of both acquired and persistent LSM with (very) late ST. METHODS AND RESULTS We searched PubMed and relevant sources from January 2002 to December 2007. Inclusion criteria were: (a) intra-vascular ultrasonography (IVUS) at both post-stent implantation and follow-up; (b) 6-9-month-follow-up IVUS; (c) implantation of either BMS or the following DES: sirolimus, paclitaxel, everolimus, or zotarolimus; and (d) follow-up for LSM. Of 33 articles retrieved for detailed evaluation, 17 met the inclusion criteria. The risk of LASM in patients with DES was four times higher compared with BMS (OR = 4.36, CI 95% 1.74-10.94) in randomized clinical trials. The risk of (very) late ST in patients with LSM (five studies) was higher compared with those without LSM (OR = 6.51, CI 95% 1.34-34.91). CONCLUSION In our meta-analysis, the risk of LASM is strongly increased after DES implantation compared with BMS. Furthermore, LSM seems to be associated with late and very late ST.

Sirolimus-eluting stents versus bare-metal stents in patients with ST-segment elevation myocardial infarction: 9-month angiographic and intravascular ultrasound results and 12-month clinical outcome results from the MISSION! Intervention Study.

OBJECTIVES Our purpose was to evaluate the efficacy and safety of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). BACKGROUND There is inconsistent and limited evidence about the efficacy and safety of drug-eluting stents in STEMI patients. METHODS A single-blind, single-center, randomized study was performed to compare bare-metal stents (BMS) with sirolimus-eluting stents (SES) in 310 STEMI patients. The primary end point was in-segment late luminal loss (LLL) at 9 months. Secondary end points included late stent malapposition (LSM) at 9 months as determined by intravascular ultrasound imaging and clinical events at 12 months. RESULTS In-segment LLL was 0.68 +/- 0.57 mm in the BMS group and 0.12 +/- 0.43 mm in the SES group with a mean difference of 0.56 mm, 95% confidence interval 0.43 to 0.68 mm (p < 0.001). Late stent malapposition at 9 months was present in 12.5% BMS patients and in 37.5% SES patients (p < 0.001). Event-free survival at 12 months was 73.6% in BMS patients and 86.0% in SES patients (p = 0.01). The target-vessel-failure-free survival was 84.7% in the BMS group and 93.0% in the SES group (p = 0.02), mainly because of a higher target lesion revascularization rate in BMS patients (11.3% vs. 3.2%; p = 0.006). Rates of death, myocardial infarction, and stent thrombosis were not different. CONCLUSIONS Sirolimus-eluting stent implantation in STEMI patients is associated with a favorable midterm clinical and angiographic outcome compared with treatment with BMS. However, LSM raises concern about the long-term safety of SES in STEMI patients.

Stent Malapposition After Sirolimus-Eluting and Bare-Metal Stent Implantation in Patients with ST-Segment Elevation Myocardial Infarction Acute and 9-Month Intravascular Ultrasound Results of the MISSION! Intervention Study

OBJECTIVES Acute and late stent malapposition (SM) after bare-metal stents (BMS) and sirolimus-eluting stents (SES) in ST-segment elevation myocardial infarction patients were studied. BACKGROUND Stent thrombosis may be caused by SM after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction patients. METHODS Post-procedure and follow-up intravascular ultrasound data were available in 184 out of 310 patients (60%; 104 SES, 80 BMS) included in the MISSION! Intervention Study. To determine the contribution of remodeling and changes in plaque burden to the change in lumen cross-sectional area (CSA) at SM sites, the change in lumen CSA (follow-up minus post-lumen CSA) was related to the change in external elastic membrane CSA (remodeling) and change in plaque and media CSA (plaque burden). RESULTS Acute SM was found in 38.5% SES patients and 33.8% BMS patients (p = 0.51), late SM in 37.5% SES patients and 12.5% BMS patients (p < 0.001). Acquired SM was found in 25.0% SES patients and 5.0% BMS patients (p < 0.001). Predictors of acute SM were reference diameter (SES: odds ratio [OR] 3.49, 95% confidence interval [CI] 1.29 to 9.43; BMS: OR 28.8, 95% CI 4.25 to 94.5) and balloon pressure (BMS: OR 0.74, 95% CI 0.58 to 0.94). Predictors of late SM were diabetes mellitus (SES: OR 0.16, 95% CI 0.02 to 1.35), reference diameter (BMS: OR 19.2, 95% CI 2.64 to 139.7), and maximum balloon pressure (BMS: OR 0.74, 95% CI 0.55 to 1.00). Change in lumen CSA was related to change in external elastic membrane CSA (R = 0.73, 95% CI 0.62 to 0.84) after SES implantation and to change in plaque and media CSA (R = -0.62, 95% CI -0.77 to -0.46) after BMS implantation. After SES implantation, acquired SM was caused by positive remodeling in 84% and plaque reduction in 16% of patients. CONCLUSIONS Acute SM was common after SES and BMS stent implantation in ST-segment elevation myocardial infarction patients. After SES implantation, late acquired SM is common and generally caused by positive remodeling.

Impact of Diabetes on Long-Term Outcome After Primary Angioplasty Insights from the DESERT cooperation

OBJECTIVE Diabetes has been shown to be associated with worse survival and repeat target vessel revascularization (TVR) after primary angioplasty. The aim of the current study was to evaluate the impact of diabetes on long-term outcome in patients undergoing primary angioplasty treated with bare metal stents (BMS) and drug-eluting stents (DES). RESEARCH DESIGN AND METHODS Our population is represented by 6,298 ST-segment elevation myocardial infarction (STEMI) patients undergoing primary angioplasty included in the DESERT database from 11 randomized trials comparing DES with BMS. RESULTS Diabetes was observed in 972 patients (15.4%) who were older (P < 0.001), more likely to be female (P < 0.001), with higher prevalence of hypertension (P < 0.001), hypercholesterolemia (P < 0.001), and longer ischemia time (P < 0.001), and without any difference in angiographic and procedural characteristics. At long-term follow-up (1,201 ± 441 days), diabetes was associated with higher rates of death (19.1% vs. 7.4%; P < 0.0001), reinfarction (10.4% vs. 7.5%; P < 0.001), stent thrombosis (7.6% vs. 4.8%; P = 0.002) with similar temporal distribution—acute, subacute, late, and very late—between diabetic and control patients, and TVR (18.6% vs. 15.1%; P = 0.006). These results were confirmed in patients receiving BMS or DES, except for TVR, there being no difference observed between diabetic and nondiabetic patients treated with DES. The impact of diabetes on outcome was confirmed after correction for baseline confounding factors (mortality, P < 0.001; repeat myocardial infarction, P = 0.006; stent thrombosis, P = 0.007; TVR, P = 0.027). CONCLUSIONS This study shows that among STEMI patients undergoing primary angioplasty, diabetes is associated with worse long-term mortality, reinfarction, and stent thrombosis in patients receiving DES and BMS. DES implantation, however, does mitigate the known deleterious effect of diabetes on TVR after BMS.

Three-year outcome of sirolimus-eluting versus bare-metal stents for the treatment of ST-segment elevation myocardial infarction (from the MISSION! Intervention Study).

To compare the long-term efficacy and safety of sirolimus-eluting stents (SES) to those of bare-metal stents (BMS) for ST-segment elevation myocardial infarction, outcomes were assessed in 310 patients (mean age age 59 +/- 11 years, 78% men) included in the randomized MISSION! Intervention Study: A Prospective Randomised Controlled Trial to Evaluate the Efficacy of Drug-Eluting Stents Versus Bare-Metal Stents for the Treatment of Acute Myocardial Infarction after a median follow-up period of 38 months. All patients were treated with aspirin (lifelong) and clopidogrel for 1 year after stent implantation. Except for a significant difference between reference vessel diameters (SES 2.76 mm vs BMS 2.92 mm, p = 0.02), there were no significant differences in baseline and angiographic characteristics between the treatment groups (158 SES, 152 BMS). A significant difference between SES and BMS patients for all revascularization end points was found after the first year of follow-up. However, at 3 years of follow-up, although there was still a trend toward better clinical outcomes in SES-treated patients, differences were no longer significant (death 4.4% vs 6.6%, p = 0.41; target vessel-related myocardial infarction 2.5% vs 4.6%, p = 0.32; target vessel revascularization 8.9% vs 15.8%, p = 0.06), target lesion revascularization 6.3% vs 12.5%, p = 0.06; and target vessel failure 12.0% vs 19.7%, p = 0.06). Three cases of very late (definite) stent thrombosis were observed in the SES group (1.9%) versus none in the BMS group (p = 0.14). In conclusion, the significant SES benefit (compared to BMS) in patients with ST-segment elevation myocardial infarctions at 1-year follow-up in terms of target vessel revascularizations decreased to some extent because of more similar target vessel revascularization rates during the 2 subsequent years. Rates of death and nonfatal recurrent MI remained comparable.

CCL3 (MIP-1α) levels are elevated during acute coronary syndromes and show strong prognostic power for future ischemic events

As chemokines are considered instrumental in thrombotic plaque rupture and erosion as well as in ischemia-reperfusion injury processes, we aimed to identify previously unknown chemokines associated with acute coronary syndromes. Plasma of 44 patients with acute myocardial infarction (AMI) and 22 controls were profiled for a panel of chemokines by multiplex analysis. Levels of CCL3 were prospectively verified in 54 patients with unstable angina pectoris (UAP). An AMI mouse model was used to assess the relationship between differentially expressed chemokines and myocardial ischemia. CCL3 levels were significantly elevated in AMI vs. controls (P=0.02) albeit, that adjustment for confounding factors attenuated this association. In support of a direct association with cardiac ischemia CCL3 levels were also seen to be elevated in patients with UAP at baseline and significantly down-regulated after 180 days (P<0.001). Importantly, baseline upper quartile levels were strongly correlated with future acute coronary syndromes (Likelihood Ratio 11.5; P<0.01). Furthermore circulating levels of CCL3 were significantly enhanced after AMI in mice (P=0.02), while CCR5(+) T-cell numbers were increased as well, suggestive of CCL3 driven T-cell homing towards the ischemic area. CCL3 levels are elevated during ACS and released upon ischemia. Since CCL3 specifically predicts future cardiovascular events, it may serve as a predictive biomarker.

Influence of Gender on Ischemic Times and Outcomes After ST-Elevation Myocardial Infarction

Previous studies investigating the influence of gender on ST-segment elevation myocardial infarction have reported conflicting results. The aim of this study was to assess the influence of gender on ischemic times and outcomes after ST-segment elevation myocardial infarction in patients treated with primary percutaneous coronary intervention in modern practice. The present multicenter registry included consecutive patients with ST-segment elevation myocardial infarctions treated with primary percutaneous coronary intervention at 3 hospitals. Adjusted mortality rates were calculated using Cox proportional-hazards analyses. In total, 3,483 patients were included, of whom 868 were women (25%). Women were older, had a higher risk factor burden, and more frequently had histories of malignancy. Men more often had cardiac histories and peripheral vascular disease. Ischemic times were longer in women (median 192 minutes [interquartile range 141 to 286] vs 175 minutes [interquartile range 128 to 279] in men, p = 0.002). However, multivariate linear regression showed that this was due to age and co-morbidity. All-cause mortality was higher at 7 days (6.0% in women vs 3.0% in men, p <0.001) and at 1 year (9.9% in women vs 6.6% in men, p = 0.001). After adjustment, female gender predicted 7 day all-cause mortality (hazard ratio 1.61, 95% confidence interval 1.06 to 2.46) and cardiac mortality (hazard ratio 1.58, 95% confidence interval 1.03 to 2.42) but not 1-year mortality. Moreover, gender was an independent effect modifier for cardiogenic shock, leading to substantially worse outcomes in women. In conclusion, ischemic times remain longer in women because of age and co-morbidity. Female gender independently predicted early all-cause and cardiac mortality after primary percutaneous coronary intervention, and a strong interaction between gender and cardiogenic shock was observed.

Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction

BACKGROUND Antiplatelet drug resistance is a well-known problem, causing recurrent cardiovascular events. Multiple genetic polymorphisms have been related to antiplatelet resistance by several large trials, however data from common clinical practice is limited. We examined the influence of previously described polymorphisms, related to aspirin and clopidogrel resistance, on treatment outcome in a real life unselected population of patients presenting with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. METHODS AND RESULTS This cohort study consisted of 1327 patients with STEMI. Patients were treated according to a standardized guideline-based protocol. Nine polymorphisms, COX1 (-842A>G), P2Y1 (893C>T), GPIa (807C>T), GPIIIa (PlA1/A2), CYP2C19 (*2, *3 and *17), ABCB1 (3435T>C) and PON1 (576A>G), were genotyped. During 1 year of follow up the primary endpoint, a composite of cardiac death or recurrent myocardial infarction, was reached in 86 patients. The COX1 and CYP2C19*2 polymorphisms were associated with the primary endpoint, HR 2.55 (95% CI 1.48-4.40), P=0.001 and HR 2.03 (1.34-3.09) P=0.001, respectively. The combined analysis demonstrated a 2.5-fold increased risk for individuals with ≥ 2 risk alleles, P=6.9 × 10(-9). The association of COX1 was driven by mortality related events whereas that of CYP2C19*2 was mainly attributed to myocardial infarction and stent thrombosis. CONCLUSION In this unselected, real life population of STEMI patient on dual-antiplatelet therapy, the polymorphisms COX1 -842A>G and CYP2C19*2 were determinants of thrombotic complications during follow-up. We show that in a clinical setting, testing for these polymorphisms could be of value in the identification of STEMI patients at risk for recurrent cardiovascular events.

Influence of coronary vessel dominance on short-and long-term outcome in patients after ST-segment elevation myocardial infarction

AIMS Prognostic importance of coronary vessel dominance in patients with ST-elevation myocardial infarction (STEMI) remains uncertain. The aim of this study was to assess influence of coronary vessel dominance on the short- and long-term outcome after STEMI. METHODS AND RESULTS Coronary angiographic images of consecutive patients presenting with first STEMI were retrospectively reviewed to assess coronary vessel dominance. Patients were followed after STEMI during a median period of 48 (IQR38-61) months for the occurrence of all-cause mortality and the composite of reinfarction and cardiac death. The population comprised 1131 patients of which 971 (86%) patients had a right dominant, 102 (9%) a left dominant, and 58 (5%) a balanced system. After 5 years of follow-up, the cumulative incidence of all-cause mortality was significantly higher in patients with a left dominant system, compared with a right dominant and balanced system (log-rank P = 0.013). Moreover, a left dominant system was an independent predictor for 30-day mortality (OR 2.51, 95% CI 1.11-5.67, P = 0.027) and the composite of reinfarction and cardiac death within 30-days after STEMI (OR 2.25, 95% CI 1.09-4.61, P = 0.028). In patients surviving first 30-days post-STEMI, coronary vessel dominance had no influence on long-term outcome. CONCLUSIONS A left dominant coronary artery system is associated with a significantly increased risk of 30-day mortality and early reinfarction after STEMI. After surviving the first 30-days post-STEMI, coronary vessel dominance had no influence on long-term outcome.

In-hospital major bleeding and its clinical relevance in patients with ST elevation myocardial infarction treated with primary percutaneous coronary intervention.

Advances in antithrombotic therapy for ST elevation myocardial infarction (STEMI) enhance the risk of bleeding. Therefore, the incidence, determinants, and prognostic implications of in-hospital major bleeding after primary percutaneous coronary intervention for STEMI were investigated. In 963 consecutive patients, the incidence of bleeding was evaluated according to commonly used classifications including Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines, Thrombolysis In Myocardial Infarction, Global Use of Strategies To Open coronary arteries, and Bleeding Academic Research Consortium. Multivariate regression analyses investigated determinants of bleeding and the relation between bleeding and 1-year all-cause mortality. Large variability in incidence existed depending on classification (1.3% to 21%). Female gender, heart rate, creatinine, multivessel disease, cardiogenic shock, and procedural failure were independently associated with bleeding. One-year mortality reached 10.2% in bleeders versus 2.0% in nonbleeders (p <0.001). Bleeding was independently associated with an increased risk of 1-year mortality (hazard ratio [HR] 2.41, p <0.017). Assessment of individual classifications confirmed the increased risk of mortality for Bleeding Academic Research Consortium (HR 2.27, p = 0.048), but not for Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the ACC/AHA guidelines, Thrombolysis In Myocardial Infarction, and Global Use of Strategies To Open coronary arteries bleeding. Thrombotic events occurred more frequently in bleeders (5.8% vs 1.5%, p <0.001); however, bleeding remained independently related to mortality with a negligible reduction in HR (2.25, p = 0.028) after adjustment. In conclusion, in-hospital major bleeding was frequently observed after STEMI, but a widespread variation in incidence existed depending on the applied definition. Patient and procedural characteristics were related to bleeding, allowing identification of high-risk patients. In-hospital major bleeding was independently associated with 1-year all-cause mortality; however, not all bleeding classifications proved equally relevant to prognosis. The relation between bleeding and mortality was shown not to be driven by the higher rate of thrombotic events among bleeders.