Initiation Of Reperfusion Therapy Research Articles

Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and myocardial reperfusion

The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the “trifecta,” defined as the presence of TFG 3, MPG 3, and complete (≥70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography.

Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and myocardial reperfusion

The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the “trifecta,” defined as the presence of TFG 3, MPG 3, and complete (≥70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography.

Treatment of the patient with acute myocardial infarction: reducing time delays.

There is a critical relationship of time to treatment and myocardial salvage in the patient with acute myocardial infarction (AMI). The challenge lies in developing a process that minimizes delays in assessment and initiation of reperfusion therapy. Three target areas were identified-time to EKG. thrombolytic therapy, and primary PTCA. A multidisciplinary team reviewed the existing standard of care and identified critical areas that were causing delays. An emergency department algorithm was developed to minimize delays, while data analysis tracked our progress. A collaborative multidisciplinary effort can reduce delays in the treatment for the patient with AMI.

The effect of heparin on tissue factor and tissue factor pathway inhibitor in patients with acute myocardial infarction

We examined plasma TF and free TFPI levels in 26 consecutive patients with AMI, 26 patients with stable exertional angina, and 25 patients with chest pain syndrome. In patients with AMI, blood samples were obtained immediately after admission and at 4, 8, 16, 24, and 48 h, and the third, fifth, seventh, and fourteenth day after initiation of reperfusion therapy. Plasma TF levels in patients with AMI on admission were significantly higher than in the chest pain syndrome and stable exertional angina groups (248.0±117.4 vs. 179.5±29.2 vs. 189.5±29.6 pg/ml, P<0.01). In patients with AMI, the level subsequently decreased after heparin administration and was maintained at significantly lower levels compared to those on admission. Plasma free TFPI levels in patients with AMI on admission were significantly higher than in the chest pain syndrome and stable exertional angina groups [33.5±12.4 vs. 26.0±7.6 ng/ml ( P<0.01) vs. 27.5±6.3 ng/ml, P<0.05]. In patients with AMI, it reached the maximum level at 4 h after the administration of heparin, and gradually decreased over the time course. These data indicated that continuous administration of a low dose of heparin was effective in decreasing TF levels without affecting TFPI levels. Our results elucidate one of the mechanisms by which the administration of heparin is beneficial in AMI patients undergoing percutaneous revascularization.

Reducing time to treatment in acute myocardial infarction.

The earliest possible initiation of reperfusion therapy is necessary to prevent extended necrosis, preserve ventricular function, and reduce morbidity and mortality from acute myocardial infarction. Therefore, improving the time to thrombolysis is a critical goal of patient management. Four complementary strategies have been employed in an attempt to shorten the time to thrombolytic therapy: (1) public education to shorten the delay in summoning help, (2) prehospital thrombolysis by trained emergency-response personnel, (3) implementation of emergency department thrombolysis protocols, (4) and the use of rapid diagnostic techniques to confirm acute myocardial infarction. Currently available fibrinolytic agents do not lend themselves to emergency use. Therefore, new thrombolytic agents have been bioengineered with characteristics that make them better suited for use in this setting. Two of these agents, TNK-t-PA and nPA, have extended half-life profiles that permit single-bolus dosing--an important consideration when fibrinolytic therapy is initiated outside the coronary care unit. The most effective system will integrate these complementary strategies to deliver continuous patient care from the time of the call for help, through emergency response, transportation, hospital admission, assessment, and initiation of thrombolytic therapy.

The use of the electrocardiogram to identify epicardial coronary and tissue reperfusion in acute myocardial infarction.

The standard 12-lead ECG gives us crucial information concerning myocardial perfusion and the success of reperfusion therapy for ST-elevation acute myocardial infarction. Continuous monitoring has advantages over repeated snapshot recordings. There are four electrocardiographic markers for prediction of the perfusion status of the ischemic myocardium: 1) ST-segment measurements; 2) T-wave configuration; 3) QRS changes; and 4) reperfusion arrhythmias. Complete and stable (> or = 70%) resolution of ST-segment elevation is associated with better outcome and preservation of left ventricular function than partial (30% to 70%) or no (< 30%) ST-segment resolution. Early inversion of the T-waves after initiation of reperfusion therapy is another marker of myocardial reperfusion and a good prognostic sign. Using standard 12-lead ECG, dynamic changes in Q-wave number, amplitude and width, R-wave amplitude and S-wave appearance are detected during reperfusion therapy. However, the significance of these changes have not been clarified. Reperfusion arrhythmias, especially bradycardia and accelerated idioventricular rhythm are detected occasionally during reperfusion therapy, but the value of reperfusion arrhythmias as a marker of coronary artery patency is still debatable. Dynamic changes in the QRS complexes, ST-segments and T-waves occur during reperfusion therapy and the days after. While changes in ST-segment amplitude have been extensively studied, the significance of QRS-complex and T-wave changes are less clear, and especially whether changes in the QRS-complex and T-wave may be complementary and additive to ST-segment monitoring. It has remained unclear whether electrocardiographic signs of reperfusion and re-ischemia should be used for therapeutic decision-making in the clinical setting.

The use of the electrocardiogram to identify epicardial coronary and tissue reperfusion in acute myocardial infarction.

The standard 12-lead electrocardiogram (ECG) gives us crucial information concerning myocardial perfusion and the success of reperfusion therapy for ST elevation acute myocardial infarction. Continuous monitoring has advantages over repeated snapshot recordings. There are four electrocardiographic markers for prediction of the perfusion status of the ischemic myocardium: (1) ST-segment measurements, (2) T-wave configuration, (3) QRS changes, and (4) reperfusion arrhythmias. Complete and stable (> or = 70%) resolution of ST-segment elevation is associated with better outcome and preservation of left ventricular function than partial (30 to 70%) or no (<30%) ST-segment resolution. Early inversion of the T waves after initiation of reperfusion therapy is another marker of myocardial reperfusion and a good prognostic sign. Using standard 12-lead ECG, dynamic changes in Q-wave number, amplitude, and width; R-wave amplitude; and S-wave appearance are detected during reperfusion therapy. However, the significance of these changes has not been clarified. Reperfusion arrhythmias, especially bradycardia and accelerated idioventricular rhythm, are detected occasionally during reperfusion therapy, but the value of reperfusion arrhythmias as a marker of coronary artery patency is still debatable. Dynamic changes in the QRS complexes, ST segments and T waves occur during reperfusion therapy and the days after. Whereas changes in ST-segment amplitude have been extensively studied, the significance of QRS-complex and T-wave changes is less clear, and especially whether changes in the QRS complex and T wave may be complementary and additive to ST-segment monitoring. It has remained unclear whether electrocardiographic signs of reperfusion and reischemia should be used for therapeutic decision making in the clinical setting.

Value of the electrocardiogram in localizing the occlusion site in the left anterior descending coronary artery in acute anterior myocardial infarction

OBJECTIVESThe study assessed the value of the electrocardiogram (ECG) as predictor of the left anterior descending coronary artery (LAD) occlusion site in relation to the first septal perforator (S1) and/or the first diagonal branch (D1) in patients with acute anterior myocardial infarction (AMI).BACKGROUNDIn anterior AMI, determination of the exact site of LAD occlusion is important because the more proximal the occlusion the less favorable the prognosis.METHODSOne hundred patients with a first anterior AMI were included. The ECG showing the most pronounced ST-segment deviation before initiation of reperfusion therapy was evaluated and correlated with the exact LAD occlusion site as determined by coronary angiography.RESULTSST-elevation in lead aVR (ST↑aVR), complete right bundle branch block, ST-depression in lead V5 (ST↓V5) and ST↑V1>2.5 mm strongly predicted LAD occlusion proximal to S1, whereas abnormal Q-waves in V4–6 were associated with occlusion distal to S1 (p = 0.000, p = 0.004, p = 0.009, p = 0.011 and p = 0.031 to 0.005, respectively). Abnormal Q-wave in lead aVL was associated with occlusion proximal to D1, whereas ST↓aVLwas suggestive of occlusion distal to D1 (p = 0.002 and p = 0.022, respectively). For both the S1 and D1, inferior ST↓ ≥1.0 mm strongly predicted proximal LAD occlusion, whereas absence of inferior ST↓ predicted distal occlusion (p ≤ 0.002 and p ≤ 0.020, respectively).CONCLUSIONSIn anterior AMI, the ECG is useful to predict the LAD occlusion site in relation to its major side branches.

Serial Changes in Plasma Levels of Soluble P-Selectin in Patients With Acute Myocardial Infarction

The present study examines whether an acute inflammatory response occurs during acute myocardial infarction (AMI) by measuring soluble P-selectin levels. We examined plasma soluble P-selectin levels in 16 consecutive patients with AMI, in 15 patients with angina, and in 13 control subjects with chest pain but normal coronary arteries and no coronary spasm. In patients with AMI, blood samples were obtained immediately after admission and at 1, 4, 24, and 48 hours, and 1 week after initiation of reperfusion therapy. The plasma soluble P-selectin levels were significantly higher in the AMI group on admission than in the other 2 groups (83 ± 13 ng/ml, p <0.01). The plasma soluble P-selectin levels at baseline were not significantly different between the angina and control groups (28 ± 4 vs 24 ± 5 ng/ml, p = NS). Plasma soluble P-selectin levels reached their peak significantly at 4 hours after initiation of the reperfusion therapy in patients with AMI. The peak level was significantly higher than the level on admission (115 ± 17 vs 83 ± 13 ng/ml, p <0.05). The plasma soluble P-selectin levels were higher in the AMI group than in the angina and control groups over the time course (p <0.01). Our data indicate that the plasma soluble P-selectin levels are increased in patients with AMI, and that the levels are increases after reperfusion therapy more than before reperfusion. We suggest that the increase in the plasma soluble P-selectin levels may be caused by the activation of endothelial cells and platelets after myocardial ischemia and reperfusion during AMI.

Flow resistance of individual neutrophils in coronary artery disease: decreased pore transit times in acute myocardial infarction.

OBJECTIVE: To investigate single neutrophil flow resistance in coronary artery disease, including myocardial infarction before initiation of reperfusion therapy. DESIGN: Neutrophil flow resistance was measured in 93 subjects in five...

Relation Between Symptom Duration Before Thrombolytic Therapy and Final Myocardial Infarct Size

Myocardial salvage is most likely to occur when thrombolytic therapy is administered within 4 to 6 hours of the onset of symptoms of myocardial infarction. The impact of delays within this early time period on final myocardial infarct size are unknown. The purpose of this study was to quantitate the relation between final myocardial infarct size and duration of symptoms before initiation of thrombolytic therapy in patients treated within 6 hours of symptom onset. The findings from patients in four prospective randomized trials of thrombolytic therapy were combined for analysis. The study population consisted of 432 patients presenting within 6 hours of onset of symptoms of first acute myocardial infarction who met ECG criteria that allowed estimation of myocardial area at risk before treatment with thrombolytic therapy and who had thallium-201 myocardial infarct-size measurements performed several weeks after infarction. ECG analysis revealed no difference in myocardium at risk for infarction as a function of duration of symptoms before initiation of thrombolytic therapy. In contrast, univariate and multivariate analysis showed that final infarct size was highly dependent on duration of symptoms before initiation of therapy. Each 30-minute increase in symptom duration before thrombolytic therapy was associated with an increase in infarct size of 1% of the myocardium. Final infarct size in patients treated 4 to 6 hours after symptom onset was indistinguishable from patients who did not receive thrombolytic therapy. These findings suggest that for patients treated within 4 to 6 hours of the onset of symptoms, there is a progressive decline in the extent of myocardium salvaged as the duration of symptoms before therapy increases. These results support efforts to minimize the time delay between symptom onset and initiation of reperfusion therapy in all eligible patients.

715-4 Thrombolytic Therapy During the “Golden Rrst Hour” in GUSTO

Data derived from thrombolytic trials performed during the placebocontrolled era have suggested that initiation of reperfusion therapy during the “golden first hour” after onset of infarction may dramatically reduce mortality and improve myocardial salvage. Pts presenting within 1 hr in these early studies may also have differed from those presenting later by having larger infarctions or more hemodynamic compromise; early therapy may thus compensate for the high-risk profile of these patients. To determine in a large contemporary cohort the extent to which early-treated pts differ with regard to baseline characteristics and clinical outcome from pts presenting later, 1269 pts (3.2% of total) randomized to 4 different thrombolytic regimens within 1 hr of symptom onset (mean 0.8 ± 0.2 hr) were compared with 38,562 pts treated between 1 and 6 hrs (mean 3.2 ± 1.6 hr) in GUSTO. &lt;1 hr 1-6 hr &lt;1 hr 1-6 hr Age (yrs) 60.1 60.9 Killip 3 or 4 (%) 2.1 2.0 Male(%) 78.8 74.8 Systolic BP (mm) 127 129 Prior Angina (%) 46.4 36.5 Pulse (bpm) 75 75 Prior MI (%) 20.7 16.1 Anterior MI (%) 43 39 Pts receiving thrombolysis early (&lt;1 hr) in the course of MI did not differ substantially with regard to severity of MI or any baseline clinical parameter from those presenting 1–6 hrs after symptom onset, except for a trend toward more frequent prior angina in the &lt;1 hr group. Mortality (30-day) was 9% lower among the first hour pts (and not different between t-PA and SK groups) than among those treated later, comparable to the overall 14% mortality reduction by t-PA compared with SK in the main trial. Thus, despite the apparent existence of a “golden first hour” during early reperfusion trials, outcome following thrombolysis during the first hour in GUSTO was only modestly better than among patients treated later.

Early detection of successful coronary reperfusion based on serum myoglobin concentration: Comparison with serum creatine kinase isoenzyme MB activity

The usefulness of serum myoglobin (Mb) concentration for early detection of successful reperfusion was compared with that of creatine kinase isoenzyme MB (CKMB) activity in 49 patients with acute myocardial infarction. To determine accurately the time of reperfusion, we performed coronary angiography every 5 minutes during reperfusion therapy. Reperfusion was obtained in 32 patients (reperfused group) but not in 17 patients (nonreperfused group) until 60 minutes after the initiation of reperfusion therapy. Blood samples were taken before and 15, 30, and 60 minutes after the angiographic confirmation of reperfusion in the reperfused group. In the nonreperfused group, samples were taken before and 15, 30, and 60 minutes after the initiation of treatment. We calculated the Mb ratio (value after reperfusion or treatment initiation to value before) and CKMB ratio (value after to value before). When values >2.4 for the Mb ratio or >2.0 for the CKMB ratio were used as the criteria for reperfusion within 60 minutes after initiation of treatment, the sensitivities were 91% and 56% at 15 minutes after reperfusion, 97% and 84% at 30 minutes, and 100% and 100% at 60 minutes, respectively. For each ratio the specificity of detection was 100% at all times evaluated. Thus the Mb ratio accurately detected the success of reperfusion as early as 15 minutes after reperfusion and may be more useful than the CKMB ratio for detecting the success of reperfusion within 30 minutes.