Prediction of cardiogenic shock using plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone [corrected] concentrations in ST elevation myocardial infarction: an analysis from the ASSENT-4 Percutaneous Coronary Intervention Trial.

OBJECTIVE: Cardiogenic shock is a major cause of death in ST elevation myocardial infarction. We investigated whether determination of plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone in the acute phase of ST elevation myocardial infarction could identify patients prone to development of cardiogenic shock. DESIGN: Retrospective analysis of a multicenter, randomized open-label trial (ASSENT-4 PCI; ClinicalTrials.gov Identifier: NCT00168792). METHODS: Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone were determined in available stored samples of 1016 ST elevation myocardial infarction patients without signs of cardiogenic shock at randomization to primary percutaneous coronary intervention or to full-dose tenecteplase before percutaneous coronary intervention. The end point of the present analysis was in-hospital cardiogenic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 57 (5.6%) patients had cardiogenic shock during index hospitalization. In-hospital cardiogenic shock increased precipitously with higher baseline concentrations of plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone (B-type natriuretic peptide and the N-terminal fragment of its pro-hormone < or =67 pg/mL: 1.9%; 68-1482 pg/mL: 5.9%; >1482 pg/mL: 14.9%; p < .001). Higher plasma [corrected] B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations were predictors of in-hospital shock, especially among those patients with relatively low clinical risk (no requirement of inotropic support before angiography, systolic blood pressure >100 mm Hg, heart rate <100 bpm, Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score of <122). In multivariate Cox regression analysis, higher plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations remained significant predictors of shock, in addition to age, systolic blood pressure, heart rate, and randomization to facilitated percutaneous coronary intervention and Killip classification. Furthermore, plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone significantly predicted in-hospital shock independently of the validated Global Utilization of Streptikonase and Tissue-Plasminogen Activator for Occluded Coronary Arteries score (p = .014). CONCLUSION: Plasma B-type natriuretic peptide and the N-terminal fragment of its pro-hormone concentrations measured early in the acute phase of ST elevation myocardial infarction are useful in predicting the development of in-hospital cardiogenic shock.

Plasma N-terminal fragment of the prohormone B-type natriuretic peptide concentrations in relation to time to treatment and Thrombolysis in Myocardial Infarction (TIMI) flow: a substudy of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial.

BACKGROUND: We investigated the prognostic significance of plasma N-terminal fragment of the prohormone B-type natriuretic peptide (Nt-proBNP) concentrations in addition to time to reperfusion and Thrombolysis in Myocardial Infarction (TIMI) flow before and after coronary intervention in patients with ST elevation myocardial infarction (STEMI) from the database of the Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT IV-PCI) trial. METHODS: Plasma Nt-proBNP was available in 1,037 patients with STEMI. Patients were randomized either to primary (p-PCI) or to full-dose tenecteplase before PCI (f-PCI).The study end point was the composite of death, cardiogenic shock, or congestive heart failure at 90 days. RESULTS: According to classification tree analysis, patients with Nt-proBNP levels >694 pg/mL had the highest primary end point rates (33.8% vs 11%, P < .001). In Cox regression analysis, Nt-proBNP >694 pg/mL strongly predicted 90-day survival even among patients with short treatment delay (f-PCI < or =3 hours: hazard ratio [HR] 2.63, P = .002 and p-PCI < or =3 hours: HR 4.87, P < .001, respectively). Patients with TIMI 3 flow after coronary intervention were at significantly higher risk of the primary end point if admission Nt-proBNP exceeded 694 pg/mL (f-PCI: HR 2.88, P < .001 and p-PCI: HR 3.84, P < .001, respectively). In multivariable analysis, Nt-proBNP >694 pg/mL significantly (P = .001) predicted 90-day survival in addition to age (P < .001), TIMI flow after PCI (P < .001), body mass index (P = .026), anterior wall infarction (P = .035), and systolic blood pressure at randomization (P = .036), respectively. CONCLUSION: Elevated plasma concentrations of Nt-proBNP in the early phase of STEMI determine in-hospital and 90-day outcome after infarction irrespective of time to treatment and pre- or postinterventional TIMI flow.

The impact of place of enrollment and delay to reperfusion on 90-day post-infarction mortality in the ASSENT-4 PCI trial: assessment of the safety and efficacy of a new treatment strategy with percutaneous coronary intervention.

OBJECTIVES: We have performed a retrospective analysis of the data stratified by time to treatment and by enrollment site: percutaneous coronary intervention hospitals (PCIH), nonpercutaneous coronary intervention hospitals (NoPCIH), or in a pre-hospital setting (PreH). BACKGROUND: The ASSENT-4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention) trial intended to test the hypothesis that in ST-segment elevation myocardial infarction (STEMI) patients an upfront fibrinolytic bolus before PCI ("facilitated PCI") compared with primary PCI would benefit STEMI patients facing a long pre-PCI delay. METHODS: Seven hundred forty-nine patients (45%) presented directly to PCIH, 578 (34%) presented to NoPCIH, and 334 (20%) were randomized and initially treated in the PreH setting. RESULTS: Patients in the PreH-facilitated group had the shortest delays (pain-to-fibrinolytic treatment 125 min) and the lowest 90-day mortality (3.1%). Among patients randomized to primary PCI, the shortest time from pain to first balloon was similarly in the PreH group (223 min). They had the lowest mortality of the primary PCI patient groups (4.1%). The highest mortality (8.4%) was in patients presenting to a PCIH and assigned to the facilitated strategy. Their pain-to-lysis time was 174 min and pain-to-PCI time 266 min (or 92 min after lysis). CONCLUSIONS: Few patients fit the target population, long delays to PCI for whom facilitated PCI was designed. Patients treated early after pain onset in the PreH setting do well after a facilitated approach. Despite limitations of post hoc subgroup analysis, these observations suggest caution in extrapolating the results of the ASSENT-4 trial to the "real world" where many patients might have potentially short pain-to-fibrinolysis time but are facing a long transport time to primary PCI.

Impact of time to therapy and reperfusion modality on the efficacy of adenosine in acute myocardial infarction: the AMISTAD-2 trial.

AIMS: The purpose of this analysis was to determine whether the efficacy of adenosine vs. placebo was dependent on the timing of reperfusion therapy in the second Acute Myocardial Infarction Study of Adenosine (AMISTAD-II). METHODS AND RESULTS: Patients presenting with ST-segment elevation anterior AMI were randomized to receive placebo vs. adenosine (50 or 70 microg/kg/min) for 3 h starting within 15 min of reperfusion therapy. In the present post hoc hypothesis generating study, the results were stratified according to the timing of reperfusion, i.e. > or = or < the median 3.17 h, and by reperfusion modality. In patients receiving reperfusion < 3.17 h, adenosine compared with placebo significantly reduced 1-month mortality (5.2 vs. 9.2%, respectively, P = 0.014), 6-month mortality (7.3 vs. 11.2%, P = 0.033), and the occurrence of the primary 6-month composite clinical endpoint of death, in-hospital CHF, or rehospitalization for CHF at 6 months (12.0 vs. 17.2%, P = 0.022). Patients reperfused beyond 3 h did not benefit from adenosine. CONCLUSION: In this post hoc analysis, 3 h adenosine infusion administered as an adjunct to reperfusion therapy within the first 3.17 h onset of evolving anterior ST-segment elevation AMI enhanced early and late survival, and reduced the composite clinical endpoint of death or CHF at 6 months.

A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II).

OBJECTIVES: The purpose of this research was to determine the effect of intravenous adenosine on clinical outcomes and infarct size in ST-segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy. BACKGROUND: Previous small studies suggest that adenosine may reduce the size of an evolving infarction. METHODS: Patients (n = 2,118) with evolving anterior STEMI receiving thrombolysis or primary angioplasty were randomized to a 3-h infusion of either adenosine 50 or 70 microg/kg/min or of placebo. The primary end point was new congestive heart failure (CHF) beginning >24 h after randomization, or the first re-hospitalization for CHF, or death from any cause within six months. Infarct size was measured in a subset of 243 patients by technetium-99m sestamibi tomography. RESULTS: There was no difference in the primary end point between placebo (17.9%) and either the pooled adenosine dose groups (16.3%) or, separately, the 50-microg/kg/min dose and 70-microg/kg/min groups (16.5% vs. 16.1%, respectively, p = 0.43). The pooled adenosine group trended toward a smaller median infarct size compared with the placebo group, 17% versus 27% (p = 0.074). A dose-response relationship with final median infarct size was seen: 11% at the high dose (p = 0.023 vs. placebo) and 23% at the low dose (p = NS vs. placebo). Infarct size and occurrence of a primary end point were significantly related (p < 0.001). CONCLUSIONS: Clinical outcomes in patients with STEMI undergoing reperfusion therapy were not significantly improved with adenosine, although infarct size was reduced with the 70-microg/kg/min adenosine infusion, a finding that correlated with fewer adverse clinical events. A larger study limited to the 70-microg/kg/min dose is, therefore, warranted.

Glycoprotein IIb/IIIa receptor antagonists in the treatment of acute ST elevation MI: from hypotheses to unexpected recent observations.

The clinically available IIb/IIIa antagonists have been studied in small angiographic trials of patients who receive these adjuncts combined with reduced doses of fibrinolytics for the purpose of evaluating their impact on infarct artery patency restoration in acute myocardial infarction. Larger clinical endpoint trials have then looked at some of these combinations, particularly with abciximab, to characterize mortality, morbidity and adverse event frequencies when compared with more traditional full dose fibrinolytic therapy. Similarly these agents have been evaluated (without fibrinolytics) for their potential to improve the results of mechanical reperfusion techniques. This article will summarize these experiences in terms of benefits and adverse events. The value of these drugs in STEMI seems modest at best.

How long is too long? Association of time delay to successful reperfusion and ventricular function outcome in acute myocardial infarction: the case for thrombolytic therapy before planned angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to quantify the effect of time delays to reperfusion on ventricular function after myocardial infarction. This allows one to identify a group of patients in whom a strategy using antecedent pharmacologic reperfusion therapy before planned direct angioplasty may offer significant benefit. BACKGROUND: Direct angioplasty for myocardial infarction is associated with a high rate of successful reperfusion compared with pharmacologic reperfusion. However, there is an inherent time delay to treatment with angioplasty compared with pharmacologic therapy. There currently are insufficient data to determine the consequences of incremental time delays to reperfusion on ventricular function. METHODS: We determined, by logistic regression analysis, the probability of observing a decrement in postmyocardial infarction ventricular function as a function of incremental time delays to reperfusion. RESULTS: Time delays of 30, 60, 90, or 120 minutes to reperfusion increased the likelihood of a worse ventricular function outcome by 1.1-, 1.3-, 1.5-, and 1.7-fold, respectively (P <.02). The upper 95% confidence limits around these odds ratios are as high as 1.3 or 2.7 for 30- and 120-minute delays, respectively. Time from symptom onset to patency remained a significant determinant of ventricular function after adjustment for clinical and procedural factors. CONCLUSIONS: Delay in time to reperfusion, measured in minutes, results in significant loss of ventricular function after myocardial infarction. Interventional strategies designed for treatment of myocardial infarction when "door-to-balloon" time is expected to exceed 60 minutes should strongly consider incorporation of pharmacologic reperfusion therapy into the therapeutic paradigm.

Predictors of door-to-balloon delay in primary angioplasty.

In the treatment of acute myocardial infarction, delayed reperfusion therapy is associated with increased mortality. Predictors of delay have been described for fibrinolysis but not for primary percutaneous transluminal coronary angioplasty (pPTCA). Therefore, we studied 40,017 consecutive patients with acute myocardial infarction who underwent pPTCA in the National Registry of Myocardial Infarction between June 1994 and April 2000. Median door-to-balloon times were calculated, and factors independently associated with a delay of >120 minutes were determined by logistic regression. The median door-to-balloon time among all patients was 111 minutes (interquartile range 84 to 152). The proportion of patients with a delay of >2 hours was greater among those aged > or = 65 years (49% vs 41%), women (50% vs 42%), patients with contraindications to fibrinolysis (60% vs 41%), and those without chest pain on admission (61% vs 43%, all p <0.0001). Delay was also more common with transfer from another hospital (87% vs 38%), with presentation outside the hours of 8 A.M. to 4 P.M. (51% vs 38%), and in hospitals performing <49 pPTCAs/year (47% vs 41%, all p <0.0001). The strongest independent predictor of delay was hospital transfer, along with non-daytime presentation and low-volume centers. Older age, female sex, and non-white race were weaker predictors. Both patient and hospital factors are associated with delay in pPTCA after presentation. These findings may help design treatment algorithms to minimize delay, thus improving the survival benefit of pPTCA. These results may also help design trials of combination reperfusion strategies.

Routine, Early, Coronary Angiography Following Thrombolysis for Acute Myocardial Infarction.

Over the last decade the use of thrombolytic therapy for patients with acute myocardial infarction has resulted in a substantial mortality reduction. While the utility of thrombolytic therapy is now widely recognized, the role of post-infarction coronary angiography remains controversial. In this report we examine the early studies which investigated the necessity and timing of angiography following thrombolysis, and review recent data that underscore the importance of achieving early infarct-related arterial patency. In place of a strategy of "selective angiography," we present an argument for routine, early coronary angiography following thrombolytic therapy for acute myocardial infarction.