Comparison of radionuclide and enzymatic estimate of infarct size in patients with acute myocardial infarction

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.     

Determinants of infarct size in reperfusion therapy for acute myocardial infarction.

BACKGROUND. Experimental animal studies have demonstrated that myocardium at risk, residual collateral flow, and duration of coronary artery occlusion are important determinants of final infarct size. The present study examined these variables in patients with acute myocardial infarction in relation to final infarct size. METHODS AND RESULTS. Myocardium at risk was assessed with hexakis(2-methoxyisobutyl isonitrile) technetium (I) (99mTc sestamibi) in 89 patients with first-time myocardial infarction (anterior, 48 patients; inferior, 41 patients). All patients had successful reperfusion therapy with either intravenous thrombolysis (32 patients) or primary coronary angioplasty (57 patients) within 24 hours of the onset of chest pain (4.7 +/- 3.9 hours; range, 0.5-21.5 hours) documented by coronary angiography. 99mTc sestamibi was injected intravenously before reperfusion therapy, and tomographic imaging was performed 1-6 hours later. Myocardium at risk was quantitated for each patient and expressed as a percentage of the left ventricle: 35 +/- 19%; range, 2-73%. Collateral flow was estimated by both invasive and noninvasive methods. Fifty-three patients with TIMI grade 0 or I flow who underwent primary coronary angioplasty had collateral flow graded angiographically (0-3) before the first balloon inflation. All patients had collateral flow estimated noninvasively from the acute sestamibi short-axis profile curve by three methods that assess the severity of the perfusion defect. Each of these three methods was significantly associated with angiographic collateral grade. Final infarct size was determined at hospital discharge by a second sestamibi study (17 +/- 17%; range, 0-59%). Myocardium at risk (r = 0.61, p less than 0.0001), angiographic collateral grade (p = 0.0003), and radionuclide estimates of collateral flow (r = 0.69-0.70, all p less than 0.0001) were all significantly associated with final infarct size. The time to reperfusion therapy was not significantly associated with final infarct size by univariate analysis (r = 0.18, p = 0.10). Two multivariate models were constructed to determine which variables were independently associated with final infarct size. In the invasive model, myocardium at risk, angiographic collateral grade with an interaction term for infarct location, and time to reperfusion were all independently significant and accounted for 70% of the variability in final infarct size. The noninvasive model, which substituted a radionuclide estimate of collateral flow for angiographic collateral grade, showed nearly identical results, accounting for 68% of the variability in infarct size in patients where the infarct artery was known to be occluded. When all patients were included (patients with and without acute angiography), the noninvasive model accounted for 59% of the variability in infarct size. CONCLUSIONS. Myocardium at risk, collateral flow, and duration of coronary occlusion are each independently associated with final infarct size and account for most of its variability. Ideally, all three parameters should be examined in evaluation of the efficacy of new treatment strategies for acute myocardial infarction.     

血清促红细胞生成素水平与急性心肌梗死患者梗死面积有关

目的观察血清促红细胞生成素（EPO）水平与急性心肌梗死（AMI）直接经皮冠状动脉介入（PCI）治疗后梗死面积的关系。方法初次急性ST段抬高型心肌梗死86例,在发病12 h内成功地接受了PCI的患者测定血清EPO和肌酸肌酶（CK）,并计算其CK累积释放量。以EPO中间值（19.6 U/L）分为高EPO组[（39±17）U/L]和低EPO组[（14±4）U/L],对两组CK累计释放量进行比较,并对CK累积释放量的可能影响因素做多元逐步回归分析。结果CK累积释放量在血清高EPO组明显低于低EPO组[（1 150±226）μkat/（L.h）vs（1 740±210）μkat/（L.h）,P<0.05)]。多元逐步回归分析显示,血清EPO水平、PCI术后TIMI血流等级和梗死前心绞痛是CK累积释放量的独立预测因子。结论内源性EPO水平高者AMI成功地直接PCI术后梗死面积较少,两者呈负相关。     

Limitation of enzymatic models for predicting myocardial infarct size.

The possibility of predicting myocardial infarct size from early enzyme measurements was studied using a physiological two compartment distribution model. Based on this the time dependent appearance function in plasma was calculated for creatine kinase, aspartate aminotransferase, and lactate dehydrogenase in 29 patients suffering from acute myocardial infarction. On average, the appearance function of the three enzymes started four hours after the onset of symptoms, and the maximum was reached after 12 hours for creatine kinase, 13 hours for aspartate aminotransferase, and 22 hours for lactate dehydrogenase. The cumulated appearance function was used as an acceptable estimate of infarct size. The prediction of infarct size from defined points of the appearance function curve for each of the three enzymes was attempted according to a set schedule during the first 25 hours after the onset of myocardial infarction. The prediction using creatine kinase was superior to the other enzymes. Even so, a reliable prediction could only be established at the very earliest from nine hours and this is too late, as irreversible loss of myocardium occurs rapidly after the onset of symptoms. This, together with the fact that other models have unacceptable variability of the prediction, lead to the conclusion that enzymatic predictive models are of no practical value in clinical intervention studies to reduce infarct size.     

Reducing infarct size in the setting of acute myocardial infarction

Acute myocardial infarction is caused by coronary occlusion, and the mainstay of treatment has become reperfusion by either coronary angioplasty with possible stenting or surgical bypass grafting. Unfortunately, reperfusion can seldom be done soon enough to prevent infarction. Thus, the search for effective cardioprotection has been ongoing for more than 3 decades. After establishment of a suitable animal model to test the efficacy of pharmacological agents and other interventions, investigators found ischemic preconditioning to be a powerful and reproducible cardioprotectant. Much of the signaling pathway from cell receptor to end-effector has now been established even if the identity of the latter has not been proven. Remarkably, the actual protection is believed to occur during reperfusion rather than during ischemia. Yet, the clinical applicability of ischemic preconditioning is limited because of the obligate need to initiate it before ischemia. However, several strategies have been developed that can be applied at the time of reperfusion and which, therefore, hold clinical promise. These interventions are thought to trigger the same signaling cascades as ischemic preconditioning, which include activation of extracellular signal-regulated kinase and phosphatidylinositol 3-kinase and also somehow prevent mitochondrial permeability transition pore formation. Ultimately, deployment of any of these strategies for clinical use must involve the pharmaceutical industry, which is becoming increasingly reluctant to be involved. Before any approach is tested in the clinical arena, however, it should be thoroughly vetted in preclinical settings. Only then can industry maximize the chances that its application in man will have the highest chance of success.     

Metabolic syndrome in patients with acute myocardial infarction is associated with increased infarct size and in-hospital complications.

BACKGROUND: Metabolic syndrome (MS), the combination of hypertension, obesity, dyslipidemia, and insulin resistance, is a precursor of diabetes mellitus (DM) and highly prevalent among patients with acute myocardial infarction (AMI). Diabetes mellitus is associated with larger infarct size and worse outcomes after AMI. This study examined infarct size and short-term outcomes among nondiabetic patients with MS following contemporary treatment of AMI. METHODS: Four hundred five consecutive patients with AMI treated with primary percutaneous coronary intervention were evaluated. Patients with diabetes (n=105) were excluded. Those with MS (n=167) included patients with three or more of the following criteria: hypertension, elevated fasting blood glucose, hypertriglyceridemia, low high-density lipoprotein, and obesity [body mass index (BMI)> or =30]. The control group (n=133) included patients without MS or DM. RESULTS: Baseline characteristics were similar except for hypertension, BMI, and dyslipidemia, which by study design were higher in the MS group. The MS group had larger infarct size as determined by peak creatine kinase-MB (79.8+/-133.8 vs. 30.84+/-51.5, P<.001). Overall in-hospital complications were higher in patients with MS (21.1% vs. 9.2%, P=.003). Metabolic syndrome is associated with a 10-fold increased risk of acute renal failure after myocardial infarction (7.9% vs. 0.8%, P=.007). CONCLUSION: Metabolic syndrome in nondiabetic patients with AMI is associated with larger infarct size, more in-hospital complications, and a marked increase of acute renal failure. Awareness of MS and preventative measures is crucial in this population to minimize infarct size and decrease morbidity after AMI.     

Ventricular fibrillation threshold in acute myocardial infarction and its relation to myocardial infarct size.

The effect of myocardial infarct size on ventricular fibrillation threshold (VFT) was evaluated by determining changes in VFT during acute myocardial infarction and relating those changes to infarct size. Infarct size was estimated from gross measurement and from serial changes in serum CPK activity in 25 dogs. VFT reduction correlated well with gross infarct size (r=0.92). This suggests that the severity of electrical instability during AMI is related to the size of the developing infarct, and that appropriate therapeutic interventions to reduce infarct size during this time may also render the heart more electrically stable.     

Determinants of infarct size after thrombolytic treatment in acute myocardial infarction

Both experimental and single-center clinical studies have shown that myocardium at risk, residual collateral flow, and duration of coronary occlusion are important determinants of final infarct size. The purpose of this study was to replicate these results on a multicenter basis to demonstrate that perfusion imaging using different camera and computer systems can provide reliable assessments of myocardium at risk and collateral flow. Sequential tomographic myocardial perfusion imaging with technetium-99 (Tc-99m) sestamibi was performed in 74 patients with first time myocardial infarction, who were enrolled in a multicenter, randomized, double-blind, placebo-controlled pilot study of poloxamer 188 as ancillary therapy to thrombolysis. All patients underwent thrombolysis within 6 hours of the onset of chest pain. Tc-99m sestamibi was injected intravenously at the initiation of thrombolytic therapy, and tomographic imaging was performed 1 to 6 hours later to assess myocardium at risk. Collateral flow was estimated noninvasively from the acute sestamibi images by 3 methods that assess the severity of the perfusion defect. Final infarct size was determined at hospital discharge by a second sestamibi study. Myocardium at risk (r = 0.61, p <0.0001) and radionuclide estimates of collateral flow (r = 0.58 to 0.66, all p <0.0001) were significantly associated with final infarct size. These associations were independent of the treatment center. On a multivariate basis, myocardium at risk (p = 0.003), the radionuclide estimate of collateral flow (p = 0.03), and treatment arm (p = 0.04) were all independent determinants of infarct size. Time to thrombolytic therapy showed only a trend (p = 0.10). The treatment center was not significant (p = 0.42). Myocardium at risk and collateral flow are important determinants of infarct size that are independent of treatment center. Tomographic imaging with Tc-99m sestamibi can provide noninvasive assessments of these parameters in multicenter trials of thrombolytic therapy.     

Quantification of infarct size by 201Tl single-photon emission computed tomography during acute myocardial infarction in humans. Comparison with enzymatic estimates

We prospectively investigated whether 201Tl single-photon emission computed tomography (SPECT) could accurately diagnose the presence and quantify the extent of acute myocardial infarction when compared with infarct size assessed by plasma MB-creatine kinase activity. Thirty patients with enzymatic evidence of infarction were imaged within 12-36 hours of chest pain (mean, 23.4 hours). No patient had a previous infarction, and none underwent intervention seeking to restore coronary patency. Infarct size was quantified with computer-generated polar maps of the myocardial radioactivity and expressed as a percentage of the total left ventricular volume. To assess left and right ventricular performance, blood-pool gated radionuclide angiography was performed immediately after SPECT. All 30 patients had perfusion defects consistent with myocardial infarction. Scintigraphic and enzymatic estimates of infarct size correlated well for the group as a whole (r = 0.78, p less than 0.001, SEE = 9.1) but especially for those patients with anterior infarction (r = 0.91, p less than 0.001, SEE = 7.9). The poor correlation observed in patients with inferior infarction (r = 0.50, p less than 0.05, SEE = 10.0) was believed to be related to the frequent occurrence of right ventricular involvement because SPECT assessed only left ventricular damage, whereas the enzymatic method estimated the myocardial injury in both ventricles. A quantitative index of right ventricular infarct size, derived from the relation between the scintigraphic and enzymatic estimates, had a strong inverse correlation with right ventricular ejection fraction (r = -0.89, p less than 0.001, SEE = 3.6).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of praecordial ST segment mapping as an index of infarct size in patients with acute myocardial infarction.

We evaluated the usefulness and limitations of praecordial ST segment mapping as a clinical means of assessing the size of acute myocardial infarction in 14 patients with anterior myocardial infarction and 13 patients with inferior myocardial infarction. sigma ST, the sum of ST segment elevations, and nST, the number of leads showing ST segment elevation, were obtained from serial electrocardiograms recorded through 39 praecordial leads. The infarct size and period of the evolution of myocardial infarction were estimated respectively from the total creatine kinase (CK) released and the serial changes of the CK releasing rate. sigma ST and nST obtained at the time when the CK release had ceased correlated closely with the total CK released. Peak sigma ST and nST, and values 48 hours after the onset of myocardial infarction, also correlated well with the total CK released; but those on admission or 12 hours after the onset correlated poorly. These results suggest that sigma ST and nST at the end of evolution of myocardial infarction or 48 hours after the onset may be two useful indices for the assessment of infarct size in patients with either anterior or inferior myocardial infarction.     

The size of infarction as judged enzymatically in 1974 patients with acute myocardial infarction. Relation with symptomatology, infarct localization and type of infarction

A common data base of six coronary care units containing personal and clinical data of 17462 patients was used to investigate the relation between clinical symptoms of patients with acute myocardial infarction and size of infarction. In 1974 of the 5110 patients, in whom a final diagnosis of infarction was made, size of infarction was determined according to serially measured levels of serum alpha-hydroxybutyrate dehydrogenase. The episode of infarction was the first in 1396 patients, was recurrent in 497, and undetermined in 81 patients. We calculated the size factor (defined as the mean size of infarction of patients with a particular symptom divided by the mean size of infarction of patients without that symptom) to evaluate the role of the size of infarction to manifestation of certain clinical symptoms. Bradycardia, shock and right-sided failure when noted on admission to the coronary care unit, had factors for size of infarction significantly greater than 1.0 (1.15, 1.79 and 1.30, respectively) in patients suffering an initial infarction, but not significantly different from 1.0 in patients with recurrent infarction. The occurrence of primary and secondary ventricular tachycardia and/or fibrillation, left heart failure (Killip class II-IV), symptomatic supraventricular tachycardia, high-degree atrioventricular blocks, ruptures and death in the coronary care unit was associated with factors significantly greater than 1.0 in those patients having both initial and recurrent infarctions. The size of infarction as judged enzymatically was significantly larger in patients with anterior than inferior and lateral infarction. The size of infarctions without Q waves was judged to be generally 35% smaller than infarctions producing Q waves. It is concluded that the size of infarction determines the occurrence of several symptoms and complications diagnosed at admission or during stay in the coronary care unit.     

Relation between electrocardiographic and enzymatic methods of estimating acute myocardial infarct size

The extent of initial acute myocardial infarction (AMI) and subsequent patient prognosis were studied using 2 independent indicators of AMI size. Two inexpensive, readily available techniques, the complete Selvester QRS score from the standard 12-lead electrocardiogram and the peak value of the isoenzyme MB of creatine kinase (CK-MB), were evaluated in 125 patients with initial AMI. The overall correlation between peak CK-MB and QRS score was fair (0.57), with marked difference according to anterior (0.72) or inferior (0.35) location. The prognostic capabilities of each measurement varied. Peak CK-MB provided significant information concerning hospital morbidity or early mortality (within 30 days) for both anterior (chi 2 = 9.83) and inferior (chi 2 = 7.68) AMI locations; however, the QRS score was significant only for anterior AMI (chi 2 = 9.50). For total 24-month mortality, the QRS score alone provided the most information (chi 2 = 10.0, p = 0.0016), which was not improved with the addition of CK-MB (chi 2 = 0.07, p = 0.79). This study shows a good relation between these 2 independent estimates of AMI size for patients with anterior AMI location. Both QRS and CK-MB results are significantly related to early morbidity and mortality; however, only the QRS score is related to total 24-month prognosis.