Arnoud W.J. van't Hof

Symptom-onset-to-balloon time and mortality in patients with acute myocardial infarction treated by primary angioplasty

OBJECTIVES The aim of the study was to evaluate the relationship between symptom-onset-to-balloon time and one-year mortality in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. BACKGROUND Despite the prognostic implications demonstrated in patients with STEMI treated with thrombolysis, the impact of time-delay on prognosis in patients undergoing primary angioplasty has yet to be established. METHODS Our study population consisted of 1,791 patients with STEMI treated by primary angioplasty from 1994 to 2001. All clinical, angiographic and follow-up data were collected. Subanalyses were conducted according to patient risk profile at presentation and preprocedural Thrombolysis In Myocardial Infarction (TIMI) flow. RESULTS A total of 103 patients (5.8%) had died at one year. Symptom-onset-to-balloon time was significantly associated with the rate of postprocedural TIMI 3 flow (p = 0.012), myocardial blush grade (p = 0.033), and one-year mortality (p = 0.02). A stronger linear association between symptom-onset-to-balloon time and one-year mortality was observed in non-low-risk patients (p = 0.006) and those with preprocedural TIMI flow 0 to 1 (p = 0.013). No relationship was found between door-to-balloon time and mortality. At multivariate analysis, a symptom-onset-to-balloon time >4 h was identified as an independent predictor of one-year mortality (p < 0.05). CONCLUSIONS This study shows that, in patients with STEMI treated by primary angioplasty, symptom-onset-to-balloon time, but not door-to-balloon time, is related to mortality, particularly in non-low-risk patients and in the absence of preprocedural anterograde flow. Furthermore, a symptom-onset-to-balloon time >4 h was identified as independent predictor of one-year mortality.

Recurrence of paroxysmal atrial fibrillation or flutter after successful cardioversion in patients with normal left ventricular function.

One hundred twenty-four consecutive patients (85%) with paroxysmal atrial fibrillation (AF) and 21 (15%) with atrial flutter (AFI) were studied immediately after pharmacologic or electrical cardioversion to sinus rhythm. Mean age was 59 +/- 13 years (range 23 to 79). Patients with reduced left ventricular function were excluded from the study. After restoration to sinus rhythm, the clinical course of all patients was followed for the first recurrence of paroxysmal AF or AFI irrespective of the therapeutic approach. Mean follow-up was 23 +/- 16 months. After 12 months of follow-up, 50% of all patients remained in sinus rhythm. Univariate analysis indicated that coronary artery disease (relative risk 1.9; 95% confidence interval 0.9-3.9), history of paroxysmal AF or AFI (2.3; 1.1-5.0), female sex (2.3; 1.1-4.6), pulmonary disease (3.9; 1.9-7.6) and valvular heart disease (4.4; 2.2-8.8) were associated with an increased risk for recurrent or frequent episodes of paroxysmal AF or AFI. No predictors were found to be associated with a decrease in length of the recurrence-free period after successful conversion to sinus rhythm. Multivariate analysis identified history of AF or AFI (odds ratio 2.5; 95% confidence interval 0.9-6.4), coronary artery disease (3.1; 1.1-8.2) and female sex (3.4; 1.3-8.9) as independent predictors for recurrent or frequent episodes of paroxysmal AF or AFI. The presence of these risk factors should be taken into account when prophylactic therapy with antiarrhythmic drugs is being considered in the treatment of paroxysmal AF or AFI.

Long-term clinical outcome after a first angiographically confirmed coronary stent thrombosis: an analysis of 431 cases.

Background— There are limited data on the long-term clinical outcome after an angiographically confirmed (definite) stent thrombosis (ST). Methods and Results— Four hundred thirty-one consecutive patients with a definite ST were enrolled in this multicenter registry. The primary end point was the composite of cardiac death and definite recurrent ST. Secondary end points were all-cause death, cardiac death, definite recurrent ST, definite and probable recurrent ST, any myocardial infarction, and any target-vessel revascularization. The primary end point occurred in 111 patients after a median follow-up of 27.1 months. The estimated cumulative event rates at 30 days and 1, 2, and 3 years were 18.0%, 23.6%, 25.2%, and 27.9%, respectively. The cumulative incidence rates of definite recurrent ST, definite or probable recurrent ST, any myocardial infarction, and any target-vessel revascularization were 18.8%, 20.1%, 21.3%, and 32.0%, respectively, at the longest available follow-up. Independent predictors for the primary end point were diabetes mellitus, total stent length, severe calcification, American College of Cardiology/American Heart Association B2-C lesions, TIMI (Thrombolysis In Myocardial Infarction) flow grade <3 after percutaneous coronary intervention, and left ventricular ejection fraction <45%. The implantation of an additional coronary stent during the first ST was also associated with unfavorable outcome. Clinical outcome was not affected by the type of previously implanted stent (drug-eluting or bare-metal stent) or the category of ST (early versus late). Conclusions— The long-term clinical outcome after a first definite ST is unfavorable, with a high mortality and recurrence rate. Diabetes mellitus, left ventricular ejection fraction <45%, long total stent length, complex coronary lesions, TIMI flow grade <3 after percutaneous coronary intervention, and implantation of an additional coronary stent during the emergent percutaneous coronary intervention for the ST were associated with this unfavorable outcome.

Second-generation everolimus-eluting stents versus first-generation sirolimus-eluting stents in acute myocardial infarction. 1-year results of the randomized XAMI (XienceV Stent vs. Cypher Stent in Primary PCI for Acute Myocardial Infarction) trial.

OBJECTIVES The goal of this study was to compare the efficacy and safety of second-generation everolimus-eluting stents (EES) with first-generation sirolimus-eluting stents (SES) in primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND Drug-eluting stents (DES) in AMI are still feared for possible late and very late stent thrombosis (ST). Newer-generation DES, with more hemocompatible polymers and improved healing, may show promise regarding increased efficacy of DES with improved safety. However, no randomized trials in AMI are available. METHODS A total of 625 patients with AMI were randomized (2:1) to receive EES or SES in the XAMI (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction) trial. Primary endpoint was major adverse cardiac events (MACE) at 1 year consisting of cardiac death, nonfatal AMI, or any target vessel revascularization. The study was powered for noninferiority of EES. Secondary endpoints comprised ST rates and MACE rate up to 3 years. RESULTS The MACE rate was 4.0% for EES and 7.7% for SES; the absolute difference was -3.7% (95% confidence interval: -8.28 to -0.03; p = 0.048) and relative risk was 0.52 (95% confidence interval: 0.27 to 1.00). One-year cardiac mortality was low at 1.5% for EES versus 2.7% for SES (p = 0.36), and 1-year incidence of definite and/or probable ST was 1.2% for EES versus 2.7% for SES (p = 0.21). CONCLUSIONS In this all-comer, randomized, multicenter AMI trial, second-generation EES was noninferior to SES, and superiority for MACE was suggested. ST rate in EES at 1-year was low, but long-term follow-up and larger studies will have to show whether very late ST rates will also be improved in newer DES. (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction [XAMI]; NTR1123).

Efficacy and safety of a new selective class III antiarrhythmic agent dofetilide in paroxysmal atrial fibrillation or atrial flutter

that regional LV dysfunction is not responsible for this nonspecificity. Our results differ from those of Breithardt et al,4 who detected late potentials in only 9% of patients with normal wall motion compared with 46% of patients with regional akinesia or dyskinesia. However, the recording methodology and semiqualitative criteria for diagnosing late potentials in their study differed markedly from those currently used by most investigators2,3 and used in our report’. In addition, the results differ primarily in the higher frequency of late potentials recorded in our control group, which also exceeds the frequency of an abnormal SAECG in normal subjects reported previously in several other studies.2,5,6 However, our “normal” patients had undergone cardiac catheterization and were much older than the normal subjects in those studies, which consisted of nurses and medical residents2 or other healthy volunteers who had not undergone cardiac catheterization.5,6 Increasing age has been found recently to independently increase the incidence of late potentials,7 and probably accounts for the frequency of late potentials in our control group. This finding of a reduced positive predictive value of the SAECG in older patients has important implic;ations for the prospective value of this test, because the question of susceptibility to VT is far more likely to be raised in older patients with suspected heart disease than it is in young, healthy people.

Ambulance or in-catheterization laboratory administration of ticagrelor for primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: Rationale and design of the randomized, double-blind Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) study

Primary percutaneous coronary intervention (PCI) is the treatment of choice for patients presenting with acute ST-segment elevation myocardial infarction (STEMI). However, if catheterization facilities are not immediately available, the effectiveness of PCI can be affected by delays in transfer. Evidence suggests that antiplatelet therapy administered early, preferably in the ambulance during transfer, may provide better and earlier perfusion. Ticagrelor, a direct platelet P2Y12 receptor inhibitor, is indicated for the management of patients with acute coronary syndromes. The ATLANTIC study (NCT01347580; EudraCT 2011-000214-19) is a 30-day international, randomized, parallel-group, placebo-controlled study in male and female patients (aged ≥18 years) who are diagnosed as having STEMI, with intended primary PCI. In total, 1770 patients will be randomized immediately after diagnosis to prehospital administration of ticagrelor 180 mg followed by matching placebo administered in hospital, or prehospital administration of placebo followed by ticagrelor 180 mg administered in hospital. All patients will then receive ticagrelor 90 mg twice daily for 30 days. The coprimary end point is the percentage of patients reaching thrombolysis in myocardial infarction flow grade 3 in the infarct-related artery at initial angiography or achieving ≥70% ST-segment elevation resolution pre-PCI. The primary safety end point is major, life-threatening, or minor bleeding after ticagrelor administration. The results of this study may have an impact on future recommendations for treatment for patients with STEMI.

Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction

OBJECTIVES In this study we considered the question of whether adjunction of glucose-insulin-potassium (GIK) infusion to primary coronary transluminal angioplasty (PTCA) is effective in patients with an acute myocardial infarction (MI). BACKGROUND A combined treatment of early and sustained reperfusion of the infarct-related coronary artery and the metabolic modulation with GIK infusion has been proposed to protect the ischemic myocardium. METHODS From April 1998 to September 2001, 940 patients with an acute MI and eligible for PTCA were randomly assigned, by open-label, to either a continuous GIK infusion for 8 to 12 h or no infusion. RESULTS The 30-day mortality was 23 of 476 patients (4.8%) receiving GIK compared with 27 of 464 patients (5.8%) in the control group (relative risk [RR] 0.82, 95% confidence interval [CI] 0.46 to 1.46). In 856 patients (91.1%) without signs of heart failure (HF) (Killip class 1), 30-day mortality was 5 of 426 patients (1.2%) in the GIK group versus 18 of 430 patients (4.2%) in the control group (RR 0.28, 95% CI 0.1 to 0.75). In 84 patients (8.9%) with signs of HF (Killip class > or =2), 30-day mortality was 18 of 50 patients (36%) in the GIK group versus 9 of 34 patients (26.5%) in the control group (RR 1.44, 95% CI 0.65 to 3.22). CONCLUSIONS Glucose-insulin-potassium infusion as adjunctive therapy to PTCA in acute MI did not result in a significant mortality reduction in all patients. In the subgroup of 856 patients without signs of HF, a significant reduction was seen. The effect of GIK infusion in patients with signs of HF (Killip class > or =2) at admission is uncertain.

Prognostic importance of creatine kinase and creatine kinase–MB after primary percutaneous coronary intervention for ST-elevation myocardial infarction

BACKGROUND Although the prognostic significance of creatine kinase (CK) and creatine kinase-MB (CK-MB) after myocardial infarction has been established after thrombolysis or no reperfusion therapy, there is limited evidence of the prognostic importance after primary percutaneous coronary intervention (PCI). METHODS In this prospective, observational study, individual data from all patients who survived at least 2 days after primary PCI between 1991 and 2004 in our hospital were recorded. The association between enzymatic infarct size (examined by peak CK and peak CK-MB levels, each divided into tertiles) and both left ventricular ejection fraction (LVEF) and 1-year mortality was evaluated. RESULTS In the study group of 4670 patients, mean peak CK was 2327 U/L (SD 2008) and mean peak CK-MB was 244 U/L (SD 208). Both increased CK and CK-MB were associated with a lower LVEF. A total of 252 patients (5.4%) died between 2 days and 1 year after admission. Both peak CK and peak CK-MB were higher in those who died. Particularly, patients in the highest tertile of either peak CK or peak CK-MB had increased mortality, whereas the differences between the lower tertiles were not significant. In 2738 patients, after multivariable analysis including LVEF, the hazard ratio for 1-year mortality in patients in the highest CK tertile was 2.28 (95% CI 1.32-3.91) and for CK-MB, 1.91 (95% CI 1.11-3.26), compared to those in the other tertiles. CONCLUSIONS According to this large-scale study, peak CK and peak CK-MB are comparable independent predictors of LV function and 1-year mortality in patients after primary PCI.

Comparison of Rapamycin- and Paclitaxel-Eluting Stents in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction

Compared with bare metal stents, sirolimus- and paclitaxel-eluting stents (SESs and PESs, respectively) have been shown to improve angiographic and clinical outcomes after percutaneous coronary intervention (PCI) in elective patients and those with ST-elevation myocardial infarction (STEMI). The aim of the present study was to compare SESs with PESs in patients with STEMI undergoing primary PCI. Patients with STEMI were randomized 1:1 to receive SESs (n = 196) or PESs (n = 201). The primary end point was late lumen loss at 9-month follow-up by quantitative coronary angiography. Secondary end points were major adverse cardiac clinical events (death, reinfarction, target vessel revascularization) at 1 month and 9 and 12 months. Three hundred ninety-seven patients with STEMI were randomized. The 2 groups had comparable baseline clinical and angiographic characteristics. Mortality was low, 1.5% after 30 days, 2.3% after 9 months, and 3.1% after 1 year. There was no difference in any clinical outcome at any follow-up period between the 2 treatment groups. Follow-up angiography was completed in 272 of 397 patients (69%). Mean +/- SD in-stent late loss was 0.01 +/- 0.42 mm in the SES group versus 0.21 +/- 0.50 mm in the PES group (difference -0.20 mm, p = 0.001). In conclusion, in patients with STEMI, primary PCI with SESs results in less late loss compared with PESs. However, these benefits did not translate into a significant decrease in major adverse cardiac events at 1-year follow-up.

Limitation of myocardial infarct size after primary angioplasty : Is a higher patency the only mechanism?

BACKGROUND Several studies demonstrate a better outcome after primary angioplasty compared with thrombolysis. The mechanism is assumed to be a higher rate of open infarct-related vessels. METHODS AND RESULTS We conducted a randomized trial of primary coronary angioplasty compared with thrombolysis. A total of 401 patients with acute myocardial infarction were randomly assigned to either primary angioplasty or thrombolytic therapy. Radionuclide left ventricular ejection fraction was performed before hospital discharge. Infarct size was estimated by measurement of serial lactate dehydrogenase activity (LDH Q72). Separate analyses were performed in patients with an open infarct-related vessel, either after thrombolysis or angioplasty. Baseline characteristics were comparable between the 2 treatment groups. Of the 197 patients treated with angioplasty, 176 (89%) had an open infarct-related vessel compared with 126 (62%) of the 204 patients treated with thrombolysis (P <.001). In patients with an open infarct-related vessel, those treated with primary angioplasty had a lower enzyme release compared with those treated with thrombolysis: LDH Q72 949 (748) and 1200 (1117), respectively (P <.05). Compared with angioplasty, patients treated with thrombolysis had a lower left ventricular ejection fraction. In the subgroup of patients with an open infarct-related vessel, after thrombolysis or angioplasty, patients treated with thrombolysis still had a lower ejection fraction (47% vs 50%, P <.05). Multivariate analysis, adjusting for differences in several clinical variables, did not change these results. Patients with an open infarct-related vessel and thrombolysis had a higher risk of an ejection fraction <40% compared with patients treated with primary angioplasty (relative risk 1.9, 95% confidence interval 1.0 to 2.7). CONCLUSIONS Despite successful thrombolysis, with sustained patency of the infarct-related vessel, primary angioplasty remains superior to thrombolytic therapy with regard to left ventricular function and enzymatic infarct size. This may be caused by adverse effects of fibrinolytics on infarcted myocardium.