Effects of pretreatment with clopidogrel on nonemergent percutaneous coronary intervention after fibrinolytic administration for ST-segment elevation myocardial infarction: a Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 study.

BACKGROUND: The use of routine nonemergent percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolytic therapy is unknown. We sought to evaluate the effect of nonemergent PCI on mortality among patients with STEMI treated with fibrinolytic administration and the consequence of clopidogrel pretreatment on this effect. METHODS: CLARITY-TIMI 28 randomized 3491 patients with STEMI treated with fibrinolytic administration and aspirin to clopidogrel or placebo. All patients were to undergo angiography 48 to 192 hours after randomization. Percutaneous coronary intervention was performed at the discretion of the treating physician. Nonemergent PCI, which was defined as PCI that was not precipitated by recurrent myocardial infarction, was performed in 1781 patients (55.7%). RESULTS: Nonemergent PCI did not affect 30-day mortality (2.0% vs 2.3% among patients who did not undergo PCI). However, nonemergent PCI was associated with lower mortality among patients randomized to clopidogrel (1.3% vs 2.8%, P = .04) but not among those randomized to placebo (2.6% vs 1.7%, P = .25; interaction P = .025). In multivariate modeling, PCI remained associated with lower mortality among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028). CONCLUSION: Among patients with STEMI treated with fibrinolytic administration and aspirin, nonemergent PCI was associated with lower mortality among patients pretreated with clopidogrel. These results suggest that routine nonemergent PCI is beneficial among such patients, although further confirmatory randomized studies are needed.

Effect of diabetes mellitus on five-year clinical outcomes after single-vessel coronary stenting (a pooled analysis of coronary stent clinical trials).

Diabetes mellitus (DM) increases the risk of clinically driven, repeat revascularization of the stented lesion in the first year after coronary stenting. The effect of DM on the risk of repeat revascularization of the stented lesion beyond 1 year, revascularization at other coronary sites, and clinical outcomes of cardiac death and myocardial infarction (MI) has not been reported. We pooled primary data from 4 multicenter trials of second-generation coronary stents that included 1,228 patients, 263 of whom (21%) had DM. Patients were followed annually to assess for prespecified end points, including repeat revascularization procedures, death, or MI. Repeat revascularization of the stented lesion was performed more frequently during the first year in patients with DM (16.0% vs 10.9%, p = 0.01) but decreased to a low frequency (1.8% vs 1.3% per year) thereafter in patients with and without DM. Repeat revascularization of other coronary segments was more frequent in patients with DM during the first and subsequent years (5-year rates, 32.2% vs 24.1%, p = 0.005). Cardiac death or MI was also more frequent among patients with DM (5-year rates, 25.4% vs 17.9%, p = 0.008) and remained significant after adjustment for all differences in baseline characteristics (hazard ratio 1.5, 95% confidence interval 1.1 to 2.0, p = 0.01). In conclusion, diabetic patients are at increased risk for revascularization of the stented lesion only in the first year after single-lesion stenting but are at increased risk for other clinical events, including cardiac death and MI, over the next 4 years.

Angiographic perfusion score: an angiographic variable that integrates both epicardial and tissue level perfusion before and after facilitated percutaneous coronary intervention in acute myocardial infarction.

BACKGROUND: Both epicardial and myocardial perfusion have been associated with clinical outcomes in the setting of ST elevation myocardial infarction (STEMI), and the performance of adjunctive/rescue percutaneous coronary intervention (PCI) may further improve clinical outcomes after fibrinolytic administration. METHODS: The goal was to develop a simple, broadly applicable angiographic metric that takes into account indices of epicardial and myocardial perfusion both before and after PCI to arrive at a single perfusion grade in patients undergoing cardiac catheterization after fibrinolysis. The angiographic perfusion score (APS) is the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG; 0-3) added to the TIMI myocardial perfusion grade (TMPG; 0-3) before and after PCI (total possible grade, 0-12). Failed perfusion was defined as an APS of 0 to 3, partial perfusion was defined as an APS of 4 to 9, and full perfusion was defined as an APS of 10 to 12. The APS was evaluated in patients from the Double-blind, Placebo-contolled, Multicenter Angiographic Trial of Rhumab CD18 in Acute Myocardial Infarction (LIMIT-AMI; n = 394) and Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis In Myocardial Infarction (ENTIRE-TIMI) 23 trials (n = 483), and infarct size (120-216 hours after AMI SPECT Technetium-99m Sestamibi data) was assessed in the LIMIT-AMI trial. RESULTS: The APS was associated with the incidence of death or myocardial infarction (failed, 16.7% [n = 18]; partial, 2.5% [n = 155]; full, 2.4% [n = 82]; P =.039 for trend) and larger SPECT infarct sizes (failed, median 39% [n = 10]; partial, 12% [n = 79]; and full, 8% [n = 35]; P =.002). No patient with full APS died, whereas the mortality rate was 11.1% in patients with a failed APS (P =.03). CONCLUSIONS: The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI. Partial or full angiographic perfusion scores are associated with a halving of infarct size, and no patients with full angiographic perfusion died.

Evaluation of the association of proximal coronary culprit artery lesion location with clinical outcomes in acute myocardial infarction.

Impaired coronary artery blood flow and left anterior descending (LAD) artery culprit location are angiographic variables that have been associated with poorer outcomes after fibrinolytic administration in patients with acute myocardial infarction (AMI). We hypothesized that culprit lesion location in the proximal portion of the culprit artery would also be associated with poorer clinical outcomes compared with a mid or distal location. Lesion location and clinical outcomes were evaluated in 2,488 patients from the Thrombolysis In Myocardial Infarction (TIMI) 4, 10A, 10B, and 14 trials. Proximal lesions were located before or at the first major branch of the parent artery, mid lesions were between the first and the second major branches, and all other lesions were classified as distal. Proximal lesions were associated with a higher incidence of in-hospital death or recurrent AMI compared with mid or distal lesions (10.5% [n = 478] vs 6.1% [n = 1,498] vs 3.7% [n = 511], p <0.001), and they were associated with a higher rate of in-hospital death (6.7% [n = 478] vs 3.2% [n = 1,498] vs 2.5% [n = 511], p = 0.001). In a multiple logistic regression model adjusting for TIMI flow grade, age, gender, and pulse, the planimetered distance from the ostium to the LAD culprit lesion was associated with 30-day death or recurrent AMI (odds ratio 0.79 per centimeter increase in distance down the artery, p = 0.01). Proximal culprit lesion location is associated with an increased risk of adverse outcomes after fibrinolytic administration, which is likely due to a larger area of subtended myocardium. In patients with a LAD culprit lesion, proximal lesion location is a multivariate correlate of adverse outcomes even after adjustment for coronary blood flow and other covariates.

Association of the Fibonacci Cascade with the distribution of coronary artery lesions responsible for ST-segment elevation myocardial infarction.

This is the first study to demonstrate the appearance of the Fibonacci Cascade within the distribution of coronary artery lesions in the human heart. The propensity for this ratio to appear in nature may also be because this ratio optimizes the efficiency of packing structures in a limited space in such a way that wasted space is minimized and the supply of energy or nutrients is optimized.

Ischemia detected on continuous electrocardiography after acute coronary syndrome: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial.

OBJECTIVES: The purpose of this study was to assess the relationship between ischemia detected on continuous electrocardiographic (cECG) recording and cardiovascular outcomes after acute coronary syndrome (ACS). BACKGROUND: The small size of prior studies evaluating cECG prevented full evaluation of the risk associated with ischemia across subpopulations and compared with other methods of risk stratification. Ranolazine, a new antianginal agent, reduces ischemic symptoms in patients with chronic angina and after ACS but the anti-ischemic effect, as detected by cECG, is not known. METHODS: In all, 6,560 patients hospitalized with non-ST-segment elevation ACS were randomly assigned to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. The cECG was performed for 7 days after randomization. Outcomes were followed for a median of 348 days. Clinical events that occurred during cECG recording were excluded from analysis. RESULTS: A total of 6,355 (97%) patients had cECG recordings evaluable for ischemia analysis. Patients with >or=1 episode of ischemia on cECG (n = 1,271, 20%) were at increased risk of cardiovascular death (7.7% vs. 2.7%, p < 0.001), MI (9.4% vs. 5.0%, p < 0.001), and recurrent ischemia (17.5% vs. 12.3%, p < 0.001). The relationship with cardiovascular death was independent of baseline characteristics or elevated biomarkers (adjusted hazard ratio: 2.46, p < 0.001). Ischemia on cECG was associated with significantly worse outcomes in several subgroups. Ranolazine did not reduce the rate of ischemia detected on cECG (19.9% vs. 21.0%, hazard ratio: 0.93, p = 0.21). CONCLUSIONS: In more than 6,300 patients with ACS, ischemia detected on cECG occurred frequently and was strongly and independently associated with poor cardiovascular outcomes, including cardiovascular death. Continuous ECG monitoring to detect ischemia after ACS may help to identify patients at increased risk. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes [MERLIN]; NCT00099788).

Angiographically evident thrombus following fibrinolytic therapy is associated with impaired myocardial perfusion in STEMI: a CLARITY-TIMI 28 substudy.

AIMS: The presence of residual thrombus following fibrinolytic therapy for ST-segment elevation myocardial infarction (STEMI) may predispose to greater embolization and microvascular dysfunction. METHODS AND RESULTS: We hypothesized that even in the presence of a patent epicardial artery, residual thrombus would be associated with worsened TIMI myocardial perfusion grades (TMPG), independent of epicardial flow. Data were analysed from the angiograms of 2684 patients enrolled in the CLARITY-TIMI 28 trial, with angiographically patent arteries (TIMI 2/3 flow) at a median of 88 h following fibrinolytic therapy. Thrombus in a patent epicardial artery was observed more frequently among patients with shorter times from randomization to angiography, among patients with non-left anterior descending infarctions, and among patients treated with placebo (vs. clopidogrel). Thrombus was associated with more frequent TIMI 2 flow (35.1 vs. 22.1%, P < 0.001), higher corrected TIMI frame counts (CTFC) (42 vs. 33 frames, P < 0.001), and a lower incidence of normal TMPG 3 (48.7 vs. 63.9%, P < 0.001), irrespective of treatment with clopidogrel or placebo. In multivariable analyses, thrombus remained associated with higher CTFC (P < 0.001) and worse TMPG (OR 1.6 for TMPG 0/1/2, P < 0.001) after adjustment for baseline covariates as well as known correlates of TMPG. The association between thrombus and impaired TMPG remained even after further adjustment for CTFC or TIMI flow grade. CONCLUSION: Residual angiographic thrombus following fibrinolytic therapy in STEMI patients is associated with impaired myocardial perfusion, independent of epicardial flow. This finding emphasizes the roles of platelet aggregation and distal embolization in the pathogenesis of microvascular dysfunction in STEMI.

Myocardial reperfusion: its assessment and its relation to clinical outcomes.

It has become increasingly apparent that epicardial blood flow restoration is necessary, but not sufficient, to achieve optimal clinical outcomes in the setting of acute coronary syndromes. Indeed, clinical outcomes are strongly associated with myocardial perfusion. The diagnostic tools available to assess myocardial perfusion following acute myocardial infarction and their association with clinical outcomes are reviewed here. Many simple angiographic markers--the Thrombolysis in Myocardial Infarction (TIMI) count frame, TIMI myocardial perfusion grade, pulsatile flow--are all readily available measures and are strongly related to clinical outcomes. Other tools, while accurate, remain limited by their high cost, low availability, and complexity for routine use.

Association of epicardial and tissue-level reperfusion with left ventricular end-diastolic pressures in ST-elevation myocardial infarction.

Unfavorable hemodynamics among patients with ST-elevation myocardial infarction (STEMI) have been associated with adverse clinical outcomes and may be linked to a failure to achieve complete reperfusion. We hypothesized that impaired epicardial and tissue-level perfusion after fibrinolytic therapy would be associated with adverse hemodynamics. The relationship between left ventricular end-diastolic pressure (LVEDP), baseline clinical characteristics, and angiographic findings were examined in 666 patients with STEMI treated with fibrinolytic therapy from the TIMI 14, INTEGRITI (TIMI 20), ENTIRE (TIMI 23), and FASTER (TIMI 24) trials. LVEDP was analyzed as a dichotomous variable with an elevated LVEDP defined as LVEDP >18 mmHg (median value). Higher post-fibrinolytic LVEDP was associated with age > or = 65, female gender, Killip Class II-IV on presentation, and LAD culprit location. Elevated LVEDP was associated with both a closed infarct-related artery (58.8% of TIMI Flow Grade (TFG) 0/1 with elevated LVEDP vs. 46.6% of TFG 2/3, p = 0.03) and impaired myocardial perfusion (55.7% of TIMI Myocardial Perfusion Grade (TMPG) 0/1 with elevated LVEDP vs. 43.8% of TMPG 2/3, p = 0.02). In a multivariate analysis, impaired myocardial perfusion (OR 1.7, p = 0.02), abnormal Killip Class (OR 4.8, p = 0.001), age > or = 65 (OR 1.6, p = 0.04), and female gender (OR 1.9, p = 0.01) were independently associated with elevated LVEDP. Elevated LVEDP was independently associated with a greater incidence of in-hospital (OR 11.8, p = 0.02) and 30-day congestive heart failure (OR 4.4, p = 0.02). In STEMI, angiographic indices of incomplete reperfusion are associated with an elevated LVEDP, and elevated LVEDP is associated with adverse clinical outcomes.