Gender-Specific Differences in All-Cause Mortality Between Incomplete and Complete Revascularization in Patients With ST-Elevation Myocardial Infarction and Multi-Vessel Coronary Artery Disease.

The best revascularization strategy (complete vs incomplete revascularization) in patients with ST-elevation myocardial infarction (STEMI) is still debated. The interaction between gender and revascularization strategy in patients with STEMI on all-cause mortality is uncertain. The aim of the present study was to evaluate gender-specific difference in all-cause mortality between incomplete and complete revascularization in patients with STEMI and multi-vessel coronary artery disease. The study population consisted of 375 men and 115 women with a first STEMI and multi-vessel coronary artery disease without cardiogenic shock at admission or left main stenosis. The 30-day and 5-year all-cause mortality was examined in patients categorized according to gender and revascularization strategy (incomplete and complete revascularization). Within the first 30 days, men and women with incomplete revascularization were associated with higher mortality rates compared with men with complete revascularization. However, the gender-strategy interaction variable was not independently associated with 30-day mortality after STEMI when corrected for baseline characteristics and angiographic features. Within the survivors of the first 30 days, men with incomplete revascularization (compared with men with complete revascularization) were independently associated with all-cause mortality during 5 years of follow-up (hazard ratios 3.07, 95% confidence interval 1.24;7.61, p = 0.016). In contrast, women with incomplete revascularization were not independently associated with 5-year all-cause mortality (hazard ratios 0.60, 95% confidence interval 0.14;2.51, p = 0.48). In conclusion, no gender-strategy differences occurred in all-cause mortality within 30 days after STEMI. However, in the survivors of the first 30 days, incomplete revascularization in men was independently associated with all-cause mortality during 5-year follow-up, but this was not the case in women.

Prognosis of complete versus incomplete revascularisation of patients with STEMI with multivessel coronary artery disease: an observational study.

OBJECTIVE: The best strategy in patients with acute ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease (CAD) regarding completeness of revascularisation of the non-culprit lesion(s) is still unclear. To establish which strategy should be followed, survival rates over a longer period should be evaluated. The aim of this study was to investigate whether complete revascularisation, compared with incomplete revascularisation, is associated with reduced short-term and long-term all-cause mortality in patients with first STEMI and multivessel CAD. METHODS: This retrospective study consisted of 518 patients with first STEMI with multivessel CAD. Complete revascularisation (45%) was defined as the treatment of any significant coronary artery stenosis (≥70% luminal narrowing) during primary or staged percutaneous coronary intervention prior to discharge. The primary end point was all-cause mortality. RESULTS: Incomplete revascularisation was not independently associated with 30-day all-cause mortality in patients with acute first STEMI and multivessel CAD (OR 1.98; 95% CI 0.62to6.37; p=0.25). During a median long-term follow-up of 6.7 years, patients with STEMI with multivessel CAD and incomplete revascularisation showed higher mortality rates compared with patients who received complete revascularisation (24% vs 12%, p<0.001), and these differences remained after excluding the first 30 days. However, in multivariate analysis, incomplete revascularisation was not independently associated with increased all-cause mortality during long-term follow-up in the group of patients with STEMI who survived the first 30 days post-STEMI (HR 1.53 95% CI 0.89-2.61, p=0.12). CONCLUSION: In patients with acute first STEMI and multivessel CAD, incomplete revascularisation compared with complete revascularisation was not independently associated with increased short-term and long-term all-cause mortality.

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.

Relation between coronary arterial dominance and left ventricular ejection fraction after ST-segment elevation acute myocardial infarction in patients having percutaneous coronary intervention.

The presence of a left dominant coronary artery system is associated with worse outcome after ST-segment elevation myocardial infarction (STEMI) compared with right dominance or a balanced coronary artery system. However, the association between coronary arterial dominance and left ventricular (LV) function at follow-up after STEMI is unclear. The present study aimed at evaluating the relation between coronary arterial dominance and LV ejection fraction (LVEF) shortly after STEMI and at 12-month follow-up. A total of 741 patients with STEMI (mean age 60 ± 11 years and 77% men) were evaluated with 2-dimentional echocardiography within 48 hours of admission (baseline) and at 12-month follow-up after STEMI. Coronary arterial dominance was assessed on the angiographic images obtained during primary percutaneous coronary intervention. A right, left, and balanced dominant coronary artery system was noted in 640 (86%), 58 (8%), and 43 (6%) patients, respectively. At baseline, significant difference in LV function was observed, with slightly lower LVEF in patients with a left dominant coronary artery system (LVEF 45 ± 8% vs 48 ± 9% and 50 ± 9%, for left dominant, right dominant, and balanced coronary artery system respectively, p = 0.03). However, at 12-month follow-up no differences in LV function or volumes were observed among the different coronary arterial dominance groups. In conclusion, patients with a left dominant coronary artery system had lower LVEF early after STEMI. At 12-month follow-up, differences in LVEF were no longer present among the different coronary arterial dominance groups.

Outcome after ST elevation myocardial infarction in patients with cancer treated with primary percutaneous coronary intervention.

The simultaneous occurrence of cancer and coronary heart disease is increasing in the Western world. Nevertheless, the influence of cancer on ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) has not been investigated extensively. This multicenter registry included patients with STEMI treated with primary PCI from 2006 to 2009. Patients were stratified according to history of cancer, and primary focus lay on all-cause and cardiac mortalities during 1-year follow-up. Adjusted effect sizes were calculated using Cox proportional hazard models. In total, 208 patients had a history of cancer (diagnosed ≤6 months ago in 20.7%, 6 months to 3 years ago in 21.7%, and >3 years ago in 57.6%) and 3,215 patients had no history of cancer. Chemotherapy had been administered previously to 23% of patients with cancer. Patients with cancer were older, more frequently women, and more commonly known with previous myocardial infarction or anemia. Reperfusion rates were similar after PCI. Patients with cancer showed greater all-cause (17.4% vs 6.5% in other patients) and cardiac mortalities at 1 year (10.7% vs 5.4% in other patients) because of high early cardiac death (23.8%) in recently diagnosed patients with cancer. After adjustment, a recent cancer diagnosis predicted cardiac mortality at 7 days (hazard ratio 3.34, 95% confidence interval 1.57 to 7.08). The adverse prognosis was partly explained by anemia and occurrence of cardiogenic shock, whereas outcome was independent of cancer treatment. In conclusion, patients with cancer showed greater mortality after STEMI. A cancer diagnosis in the 6 months before primary PCI was strongly associated with early cardiac mortality.

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.

Peak and fixed-time high-sensitive troponin for prediction of infarct size, impaired left ventricular function, and adverse outcomes in patients with first ST-segment elevation myocardial infarction receiving percutaneous coronary intervention.

The clinical use of advanced imaging modalities for early determination of infarct size and prognosis is limited. As a specific indicator of myocardial necrosis, cardiac troponin T (cTnT) can be used as a surrogate measure for this purpose. The present study sought to investigate the use of peak and serial 6-hour fixed-time high-sensitive (hs) cTnT for estimation of infarct size, left ventricular (LV) function, and prognosis in consecutive patients with ST-segment elevation myocardial infarction. The infarct size was expressed as the 48-hour cumulative creatine kinase release. LV function at 3 months was assessed using the echocardiographic wall motion score index and LV ejection fraction using radionuclide ventriculography. Adverse outcomes, comprising all-cause death, implantable cardioverter-defibrillator implantation, or hospitalization for heart failure, were recorded at 1 year of follow-up. In 188 patients, the peak and all fixed-time values correlated significantly with the 48-hour cumulative creatine kinase release, wall motion score index, and LV ejection fraction. The hs-cTnT value at 24 hours demonstrated the greatest correlation (r = 0.86, r = 0.47, and r = -0.59, respectively; p <0.001 for all). In the multivariate regression models adjusted for the clinical parameters, almost all were independently associated with the 48-hour cumulative creatine kinase release, wall motion score index, and LV ejection fraction, with the hs-cTnT value at 24 hours having the largest effect. Moreover, all cTnT values independently predicted adverse outcomes, again, with the hs-cTnT value at 24 hours showing the largest influence (hazard ratio 3.77, 95% confidence interval 2.12 to 6.73, p <0.001). In conclusion, not only peak, but all fixed-time hs-cTnT values were associated with infarct size, LV function at 3 months, and adverse outcomes 1 year after ST-segment elevation myocardial infarction. The value 24 hours after the onset of symptoms had the closest associations with all outcomes. Therefore, serial sampling for a peak value might be redundant.

Long-term outcome of second-generation everolimus-eluting stents and Endeavor zotarolimus-eluting stents in a prospective registry of ST-elevation myocardial infarction patients.

AIMS: The optimal drug-eluting stent (DES) in ST-elevation myocardial infarction (STEMI) patients remains unclear. We sought to compare the long-term performance of everolimus-eluting stents (EES) and Endeavor zotarolimus-eluting stents (E-ZES) in STEMI. METHODS AND RESULTS: The current analysis of a prospective registry included consecutive patients treated with EES or E-ZES for STEMI. Adjustment for measured confounders was done using Cox regression. In total, 931 patients met the inclusion criteria (412 EES and 519 E-ZES). Baseline characteristics were balanced, apart from a lower rate of renal insufficiency in EES. Median follow-up duration was 2.4 years (IQR 1.6-3.1). Mortality outcomes were similar. Up to three-year follow-up, the composite endpoint of cardiac death, target vessel-related myocardial infarction and target lesion revascularisation (TLR) was lower in EES; 9.7% vs. 13.7% in E-ZES (HR 0.64, 95% CI: 0.42-0.99), primarily driven by reduced TLR rates; 3.4% in EES vs. 7.3% in E-ZES (HR 0.46, 95% CI: 0.23-0.92). Definite stent thrombosis rates were low and similar between groups (1.1% in EES vs. 1.9% in E-ZES, p=0.190). CONCLUSIONS: Use of EES led to lower rates of the composite endpoint, driven by reduced TLR. This suggests that EES are more efficacious than Endeavor ZES in STEMI. Definite ST rates were low, and the strategy of second-generation DES implantation and the administration of upfront GP IIb/IIIa inhibitors appear to be safe in STEMI.

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 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.

Multimodality imaging in interventional cardiology.

'Multimodality' imaging--the side-by-side interpretation of data obtained from various noninvasive imaging techniques, such as echocardiography, radionuclide techniques, multidetector CT (MDCT), and MRI--allows anatomical, morphological, and functional data to be combined, increases diagnostic accuracy, and improves the efficacy of cardiovascular interventions and clinical outcomes. During the past decade, advances in software and hardware have allowed co-registration of various imaging modalities, resulting in cardiac 'hybrid' or 'fusion' imaging. In this Review, we discuss the roles of both multimodality and hybrid imaging in three broad areas of cardiology--coronary artery disease (CAD), heart failure, and valvular heart disease. In the evaluation of CAD, integration of either single-photon emission computed tomography (SPECT) or PET with CT coronary angiography provides both morphological and functional data in a single procedure. Accordingly, the functional consequences (myocardial hypoperfusion on SPECT or PET) of anatomical pathology (coronary anatomy on MDCT or MRI) can be assessed. Co-registration of PET and MRI data sets to provide cellular and molecular information on plaque composition and stability is now possible. Furthermore, novel imaging modalities have been implemented to guide electrophysiological and transcatheter-based procedures, such as cardiac resynchronization therapy (an established treatment for patients with heart failure), and transcatheter valve repair or replacement procedures.

Five-year clinical follow-up from the MISSION! Intervention Study: sirolimus-eluting stent versus bare metal stent implantation in patients with ST-segment elevation myocardial infarction, a randomised controlled trial.

AIMS: To evaluate the clinical outcomes of sirolimus-eluting stent (SES) versus bare metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) at long-term follow-up. METHODS AND RESULTS: After five years, 310 STEMI patients randomly assigned to implantation of either SES or BMS, were compared. Survival rates were comparable between groups (SES 94.3% vs. BMS 92.8%, p=0.57), as were the rates of reinfarction (10.6% vs. 13.7%, p=0.40), freedom of death/re-MI (84.4% vs. 79.8%, p=0.29) and target vessel failure (14.9% vs. 21.7%, p=0.11). Likewise, rates of overall stent thrombosis (ST) (5.4% vs. 2.7%, p=0.28) and very late ST (4.1% vs. 0.7%, p=0.07) did not significantly differ between the SES- and BMS-group. In 184 patients with IVUS data, definite and definite/probable VLST was more common in those with late stent malapposition versus those without late stent malapposition (4.3% and 6.6% vs. no events [p=0.018 and p=0.004], respectively). The cumulative incidences of target vessel and target lesion revascularisation (TVR and TLR) were not significantly lower in the SES-group (11.2% vs. 17.9%, p=0.09 and 7.2% vs. 12.9%, p=0.08), as was the rate of clinically driven TLR (6.6% vs. 9.5%, p=0.30). CONCLUSIONS: SES implantation was neither associated with increased rates of major adverse cardiac events, nor with a reduction in re-intervention, compared to implantation of a BMS in patients with STEMI after five years. However, a trend of more very late stent thrombosis was observed after SES implantation (ISRCTN62825862).

Asymmetric dimethylarginine (ADMA) levels display a morning peak in patients with acute myocardial infarction.

High Asymmetric Dimethylarginine (ADMA) levels are associated with increased platelet activity, elevated blood pressure, vasoconstriction and impaired vascular relaxation. We hypothesized that the myocardial infarction morning peak of occurrence is closely related to a morning peak of ADMA levels. We performed a cross-sectional study among patients with documented myocardial infarction who had been enrolled in the prospective MISSION! Intervention Study. In total, serum ADMA levels were measured in their acute setting of myocardial infarction in 120 patients. The frequency of myocardial infarction onset of symptoms and emergency coronary catheterization and the ADMA levels displayed a similar daily pattern with a morning peak between 06:00-11:59 h. The absolute ADMA levels peak was between 06:00-07:59 h with a median (interquartile range) peak value of 1.01 (0.84-1.21) µmol/L for the n=9 patients vs. 0.75 (0.61-0.89) µmol/L for the remaining 111 patients admitted throughout the rest of the 24-hour interval (p=0.003 for between groups comparison). The amplitude (95% 0.08 µmol/L (0.004-0.16) with p=0.042 for statistic model significance. In conclusion, ADMA levels display a 24-hour variation with a significant morning peak in patients with acute myocardial infarction. These findings may relate ADMA levels to the acute onset of thrombotic cardiovascular events.

The 5352 A allele of the pro-inflammatory caspase-1 gene predicts late-acquired stent malapposition in STEMI patients treated with sirolimus stents.

Late-acquired stent malapposition (LASM) is a common finding after sirolimus-eluting stent (SES) implantation and may be the cause for late stent thrombosis. Inflammation may play a pivotal role in LASM just as it plays in stent restenosis. We have therefore investigated seven polymorphisms involved in inflammatory processes, related in previous reports to restenosis, on the risk of LASM in SES patients. Patients with ST-elevation myocardial infarction who underwent SES implantation and had intravascular ultrasonography (IVUS) data available for both immediate post-intervention and 9-month follow-up were included in the present study. In total, 104 patients from the MISSION! Intervention Study were genotyped for the caspase-1 5352 G/A, eotaxin 1382 A/G, CD14 260 A/G, colony stimulating factor 2 1943 C/T, IL10 -1117 C/T, IL10 4251 C/T, and the tumor necrosis factor alpha 1211 C/T polymorphisms. LASM occurred in 26/104 (25%) of patients. We found a significantly higher risk for LASM in patients carrying the caspase-1 (CASP1) 5352 A allele (RR = 2.32; 95% CI 1.22-4.42). In addition, mean neointimal growth was significantly lower in patients carrying this LASM risk allele (1.6 vs. 4.1%, p = 0.014). The other six polymorphisms related to inflammation were not significantly related to the risk of LASM. In conclusion, carriers of the 5352 A allele in the caspase-1 gene are at increased risk of developing LASM after SES implantation. If this is confirmed in larger studies, then screening for this polymorphism in patients undergoing percutaneous coronary interventions could eventually help cardiologists to better select between commercially available stents.

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.

Structured care for patients after acute myocardial infarction: sudden cardiac death prevention--data from the Leiden MISSION! AMI study.

AIMS: To assess the number of patients in daily clinical practice that meets criteria for implantation of an implantable cardioverter defibrillator (ICD) following acute myocardial infarction (AMI) when treated according to an aggressive treatment protocol. METHODS AND RESULTS: Patients were treated according to the MISSION! protocol. The protocol encompasses pre-hospital, in-hospital, and outpatient clinical framework for the acute and chronic treatment of AMI patients and the decision making regarding primary prevention of sudden cardiac death (SCD). A total of 676 consecutive AMI patients (78% male, mean age 59 +/- 12 years) treated according to the MISSION! protocol were included in this analysis. Left ventricular ejection fraction at 3 months was 54 +/- 10%. Only 39 (6%) patients met criteria for implantation of an ICD <1 year post-MI. These patients suffered more extensive infarctions as indicated by higher peak troponin T values (mean 14.5 +/- 8.3 vs. 6.5 +/- 14.7 microg/L; P < 0.001) and had more left anterior descending artery related infarctions (79 vs. 46%; P < 0.001). Cumulative first appropriate therapy rate was 15% at 3 years follow-up. No SCD was observed in the study population. CONCLUSION: Aggressive treatment of AMI patients and close monitoring after the index event according to a standardized protocol, results in only a small number of patients becoming candidate for prophylactic ICD implantation. An easy-to-use protocol combining aggressive reperfusion, optimal medication, and a risk stratification algorithm tailored to fit within routine practice may help to maintain ICD implantation rates within manageable proportions.

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.

Myocardial infarction occurs with a similar 24 h pattern in the 4G/5G versions of plasminogen activator inhibitor-1.

PAI-1 expression is regulated by a 4G/5G promoter polymorphism. The 4G allele is associated with greater circadian variation of PAI-1 levels. We hypothesized that the 24 h variation of cardiac risk is more pronounced among persons with the 4G4G genotype than among ones with 4G5G and 5G5G genotypes. We assessed the time of onset of symptoms in 623 consecutive patients with acute myocardial infarction (AMI) enrolled in the MISSION! Study between February 1, 2004, and October 29, 2006. All of the patients were genotyped for the PAI-1 4G/5G polymorphism. We quantified the amplitude of the 24 h variation of AMI with a generalized linear model with Poisson distribution. A morning peak, between 06:00-11:59 h (n = 197; 32% of all cases), in the onset of symptoms of AMI was observed. The group composed of patients with the 4G4G genotype did not have a more pronounced morning peak than the groups composed of other genotypes; the 24 h variation was 38% (95% confidence interval 12-70%) in the group of 4G4G patients and 34% (14-58%) and 56% (20-100%) in the 4G5G and 5G5G groups of patients, respectively. Our findings show that 24 h variation of cardiac risk is not more pronounced among the 4G4G genotype of PAI-1.

Short and long-term benefits of sirolimus-eluting stent in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials.

BACKGROUND: Recent concerns have emerged on the potential higher risk of stent thrombosis after DES implantation, that might be even more pronounced among STEMI patients. The aim of the current study was to perform a meta-analysis to evaluate the benefits and safety of Sirolimus-Eluting Stent (SES) as compared to BMS in patients undergoing primary angioplasty for STEMI. METHODS: The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following keywords were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. RESULTS: A total of 9 trials were included in the meta-analysis, involving 2,769 patients (1389 or 50.2% randomized to DES and 1,380 or 49.8% randomized to BMS). At 12 months follow-up, SES was associated with a significant reduction in TVR (4.9% vs. 13.6%, p < 0.0001), with a trend in benefits in mortality (2.9% vs. 4.2%, p = 0.08) and reinfarction (3.0% vs. 4.3%, p = 0.06), without any significant difference in stent thrombosis (1.9% vs. 2.5%, p = 0.36). Safety and efficacy of DES were confirmed at 2-3 years follow-up (data available from 4 trials including 569 patients). CONCLUSIONS: This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, SES as compared to BMS is safe and associated with a significant reduction in TVR at 1 and 2-3 years follow-up.

Post-intervention IVUS is not predictive for very late in-stent thrombosis in drug-eluting stents.

OBJECTIVES: Stent thrombosis is a life-threatening complication associated with sudden death and acute myocardial infarction. Histopathologic studies have linked the occurrence of very late stent thrombosis in drug-eluting stents (DES) with delayed endothealisation and stent malapposition. Our aim was to investigate if late stent malapposition in DES could be predicted by immediate postintervention intra-vascular ultrasonography (IVUS). METHODS AND RESULTS: From our MISSION! database of 184 consecutive patients with ST-elevation myocardial infarction (STEMI) who had immediate post-intervention and nine-month follow-up IVUS examinations we prospectively identified three patients with very late (> 365 days) and definite (with angiographic evidence) in-stent thrombosis in DES. Patients had completed the twelve-month clopidogrel-aspirin dual treatment period, two of them were under aspirin therapy while the third patient had aspirin temporarily discontinued before planned surgery. When assessed by serial documentary (immediate post-intervention and nine-month) IVUS, all three patients demonstrated stent malapposition at nine months: in two cases the malapposition was acquired (immediate post-intervention IVUS showed a well apposed stent) and one case presented persistent malapposition (the stent was found malapposed both at immediate post-intervention and nine-month follow-up IVUS). CONCLUSIONS: Immediate post-intervention IVUS showing no malapposition does not guarantee an uneventful course after DES implantation.