Relation between infarct size and left ventricular performance assessed in patients with first acute myocardial infarction randomized to intracoronary thrombolytic therapy or to conventional treatment

Reperfusion of ischemic myocardium has been reported to increase the cumulative creatine kinase activity in plasma per gram of infarcted myocardium as assessed with the method of Shell et al. In an attempt to find out whether infarct size assessment using the method of Witteveen et al was affected by reperfusion, the relation between enzymatic infarct size was analyzed using Witteveen's method and left ventricular (LV) function parameters in 266 patients with first acute myocardial infarction randomized to intracoronary thrombolysis (n = 134) or conventional therapy (n = 132). Compared with patients allocated to conventional therapy, patients allocated to intracoronary thrombolysis had smaller enzymatic infarct size by 29% (p less than 0.001), smaller LV end-diastolic and end-systolic volume indexes by 10% (p less than 0.05) and 20% (p less than 0.005), respectively, and higher LV ejection fraction (55 +/- 1% vs 49 +/- 1%; p less than 0.001). The beneficial effects of thrombolytic therapy on LV performance were closely associated with thrombolysis-induced limitation of infarct size. The dependence from infarct size of LV end-diastolic volume, LV end-systolic volume, and ejection fraction was not different in the 2 therapy groups. It was concluded that Witteveen's method of infarct size assessment is not influenced by the presence of reperfusion. Therefore, this method was recommended for trials on recanalization in patients with acute myocardial infarction.     

Effects of coronary artery reperfusion on relation between creatine kinase-MB release and infarct size estimated by myocardial emission tomography with thallium-201 in man

The quantitative relations between serum creatine kinase-MB isoenzyme (CK-MB) release and the final infarct size estimated by myocardial emission computed tomography with thallium-201 was assessed in 37 patients with a first acute transmural myocardial infarction who underwent intracoronary thrombolysis using urokinase 4.6 +/- 1.9 hours after the onset of symptoms. Serial CK-MB determinations were used to calculate the accumulated release of CK-MB (sigma CK-MB). Myocardial emission tomography with thallium-201 was performed 4 weeks after the onset, and infarct volume was measured from reconstructed tomographic images by computerized planimetry. The results are presented for two groups of patients: 11 patients with unsuccessful thrombolysis (group A) and 26 patients with successful thrombolysis (group B). An excellent linear relation was found for group A (sigma CK-MB = 6.4 X infarct volume + 47.7, r = 0.91), whereas a different linear relation was observed for group B (sigma CK-MB = 10.5 X infarct volume + 89.1, r = 0.80). Moreover, serum CK-MB activity reached a peak at 21.1 +/- 2.2 hours after the onset in group A and reached an earlier peak at 12.5 +/- 2.9 hours in group B (p less than 0.001). These data suggest that acute coronary recanalization alters the kinetics of CK-MB release, resulting in greater CK-MB release into the serum for equivalent infarct volume estimated by myocardial emission tomography with thallium-201. Thus, serum CK-MB time-activity curves after acute myocardial infarction may be influenced considerably by acute reperfusion, which is an important factor that should be incorporated in the interpretation of enzymatic estimates of infarct size in human patients.     

Evaluation of healing process in myocardial infarction by the time course of serum myosin light chain I: the effects of early reperfusion]

The effects of early reperfusion on the infarct area were evaluated by measuring the plasma creatine phosphokinase (CPK) activity and myosin light chain I (LCI) in 30 patients with acute myocardial infarction. Twenty of these patients underwent coronary angiography, of whom 9 had reperfusion with successful intracoronary thrombolysis, which revealed significant correlations between peak values of LCI and peak values of CPK or CPK-MB activity (r = 0.775, p < 0.01 or r = 0.783, p < 0.01). Similarly, peak value of LCI correlated with left ventricular ejection fraction (r = -0.729, p < 0.01) and the infarct size which was estimated according to the extent and severity scores measured by Tl-201 myocardial SPECT (vs extent score, r = 0.439, p < 0.05; vs severity score, r = 0.429, p < 0.05). The time activity curves of plasma CPK activity and LCI differed in patients with and without reperfusion; in the former, mean peak values of CPK activity and LCI were 1,170 +/- 321 U/L (mean +/- SD) and 10.7 +/- 3.5 ng/ml, respectively, while in the latter, they were 5,430 +/- 3,315 U/L and 25.2 +/- 12.9 ng/ml, respectively. The times to peak values of LCI and CPK did not differ between these 2 patient groups. We concluded that the early reperfusion suppresses the progressive extension of irreversible injury in the infarct area and significantly diminishes the infarct size.     

Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate

Early appearance of positive findings on a technetium-99m pyrophosphate scan has been shown to be associated with the presence of a reperfused acute myocardial infarction (AMI). Early technetium-99m pyrophosphate imaging was performed by emission computed tomography to evaluate reperfusion and to test the feasibility of estimating infarct size soon after coronary reperfusion based on acute positive tomographic findings. Twenty-seven patients with transmural AMI who were treated with intracoronary urokinase infusion followed by percutaneous transluminal coronary angioplasty underwent pyrophosphate imaging 8.7 +/- 2.1 hours after the onset of AMI. None of the 8 patients in whom reperfusion was unsuccessful had acute positive findings. Of 19 patients in whom reperfusion was successful, 17 had acute positive findings (p less than 0.001). In these 17, tomographic infarct volumes were determined from reconstructed transaxial images. The threshold for areas of increased pyrophosphate uptake within the infarct was set at 60% of peak activity by the computerized edge-detection algorithm. The total number of pixels in all transaxial sections showing increased tracer uptake were added and multiplied by a size factor and 1.05 g/cm3 muscle to determine infarct volume. The correlations of tomographic infarct volumes with peak serum creatine kinase (CK) levels (r = 0.82) and with cumulative release of CK-MB isoenzyme (r = 0.89) were good. Moreover, the time to positive imaging was significantly shorter than that to peak CK level (8.5 +/- 2.3 vs 10.4 +/- 2.2 hours, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of myocardial infarction fraction using single photon emission computed tomography

Although infarct size correlates generally with prognosis after acute myocardial infarction, an absolute measure of infarct size may have differing prognostic significance depending on absolute left ventricular mass. To test the hypothesis that single photon emission computed tomography can accurately measure myocardial infarct size as a percent of total left ventricular mass ("infarction fraction"), thallium-201 and technetium-99m pyrophosphate tomograms were acquired in 21 dogs 24 to 48 hours after fixed occlusion of the left anterior descending or circumflex coronary artery. Pathologic infarct weight was measured as the myocardial mass that showed no staining with triphenyltetrazolium chloride. Scintigraphic infarct mass by technetium-99m pyrophosphate was calculated from the total number of left ventricular volume elements (voxels) demonstrating technetium-99m pyrophosphate uptake X voxel dimension [( 0.476 cm]3) X specific gravity of myocardium (1.05 g/cm3). Scintigraphic left ventricular mass was calculated in a similar fashion using an overlay of the thallium-201 and technetium-99m pyrophosphate scans. The "infarction fraction" was calculated as: infarction fraction = infarct mass/left ventricular mass. There was good correlation between single photon emission computed tomography and pathologic measurements of infarct mass (technetium-99m pyrophosphate mass = 1.01 X pathologic infarct mass + 0.96; r = 0.98), left ventricular mass (single photon emission computed tomographic left ventricular mass = 0.60 X pathologic left ventricular mass + 37.4; r = 0.86) and "infarction fraction" (single photon emission computed tomographic infarction fraction = 1.09 X pathologic infarction fraction - 1.7; r = 0.94).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduction of myocardial infarct size by early intracoronary thrombolysis as assessed by serum cardiac myosin light chains and left ventricular function

Cardiac myosin light chains are released from the infarcted myocardium soon after the onset of infarction, and the level of myosin light chains in the serum reflects infarct size, regardless of the presence of early coronary reperfusion. In this study, we used serum myosin light chains and assessed changes in left ventricular function to evaluate the effects of intracoronary thrombolysis on infarct size, with special reference to the interval between the onset of infarction and the time of reperfusion. Forty patients with acute myocardial infarction who underwent coronary angiography and intracoronary thrombolysis for the left anterior descending artery (LAD) early after the onset of infarction were categorized in four groups: in group A (n = 9) the LAD was already patent at the start of intracoronary thrombolysis, in group B (n = 12) antegrade flow in the LAD was achieved within three hours of the onset of symptoms, in group C (n = 10) antegrade flow was achieved later than three hours after the onset of symptoms, and in group D (n = 9) antegrade flow in the LAD was not achieved. The peak appearance time of creatine phosphokinase (CPK) in group D was significantly later than in the other groups. The total release of CPK in group C (3,119 +/- 414 IU/l) was greater than that in group A (1,332 +/- 346 IU/l) (p less than 0.01), but the total CPK release in group D (2,525 +/- 525 IU/l) was not statistically different from those of any other group. In all four groups myosin light chain I appeared in the serum from the first day on and reached their peak values between the third and fifth days. The peak values of myosin light chain I were 14.7 +/- 2.1 ng/ml for group A, 16.3 +/- 2.3 ng/ml for group B, 24.6 +/- 2.4 ng/ml for group C, and 25.1 +/- 1.8 ng/ml for group D. The peak myosin light chain levels in groups A and B were less than those in groups C and D. Twenty-nine of the 40 patients had no previous episodes of infarction, and these 29 patients were classified in two groups according to the Forrester's subset class on the first day: four of seven patients in group D were in subsets II, III or IV; whereas, the majority of patients in groups A, B and C were in subset I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dual radionuclide study of myocardial infarction. Relationships between myocardial uptake of potassium-43, technetium-99m stannous pyrophosphate, regional myocardial blood flow and creatine phosphokinase depletion.

The dual radionuclide myocardial distributions of imaging agents potassium-43 (43K) and technetium-99m stannous pyrophosphate (99mTc-PYP) were studied in a 24-hour closed chest canine infarct preparation. In multiple myocardial biopsies in 20 dogs, tissue levels of both radionuclides were compared to either an index of tissue viability (myocardial creatine phosphokinase [CPK] depletion), or to estimates of regional myocardial blood flow as measured by the microsphere technique. Myocardial 43K uptake in the ischemic and infarcted zone correlated well with both CPK depletion (r = 0.73) and microsphere estimates of relative blood flow. The correlation with microspheres was excellent in the transmural sample (r = 0.93) as well as endocardial (r = 0.97) and epicardial (r = 0.86) portions. On the other hand, 99mTc-PYP myocardial uptake did not correlate with the extent of CPK depletion. Maximal uptake was frequently noted in border zones with only moderate CPK depletion, while lesser degrees of 99mTc-PYP uptake were noted in the central infarct zone where CPK activity was lowest. The relationship of 99mTc-PYP uptake to microsphere regional flow estimates demonstrated that 99mTc-PYP uptake was maximal at flows of 0.3 to 0.4 of normal. At lower flows, 99mTc-PYP uptake fell toward normal levels. A similar relationship was noted between the distributions of 99mTc-PYP and 43K. In relatively high flow border segments (larger than or equal to 0.80 of normal), abnormal 99mTc-PYP uptake of five to six times normal persisted. The transmural distribution of 99mTc-PYP demonstrated that in low flow regions 99mTc-PYP uptake was primarily epicardial, while in the higher flow ischemic periphery of the infarct endocardial uptake predominated. Thus, while there is a direct correlation between cationic 43K myocardial uptake and regional myocardial viability and blood flow, no such direct relationship exists for 99mTc-PYP. This is in part based on the necessity for delivery of the radioactive tracer to the infarct zone.     

Coronary angiography and left ventriculography in survivors of transmural and nontransmural myocardial infarction

Recent studies have suggested a similar prognosis for patients with transmural myocardial infarction and nontransmural myocardial infarction despite a smaller infarct size in the latter patients estimated by creatine phosphokinase (CPK). Thirty-one patients with transmural myocardial infarction and 17 patients with nontransmural myocardial infarction as defined by electrocardiographic criteria underwent coronary angiography and left ventriculography from 10 to 24 days after they had an acute myocardial infarction. Forty-three of these 48 patients were asymptomatic following their myocardial infarction. When compared to patients with nontransmural myocardial infarction, those with transmural myocardial infarction had greater peak CPK levels, 1,090 +/- 210 versus 290 +/- 60 IU (p less than 0.01). There was no difference in prevalence of single, double or triple vessel coronary artery disease, mean number of coronary arteries 50 per cent narrowed (2.0 +/- 0.2 versus 2.0 +/- 0.2), near total or total occlusions, coronary score (Friesinger) (7.9 +/- 0.6 versus 8.2 +/- 0.7), left ventricular ejection fraction (48 +/- 2 versus 53 +/- 4), or per cent of akinetic-dyskinetic myocardial segments (66 of 242 [27 per cent] versus 32 of 132 [24 per cent]) between two groups. The similar extent of coronary artery narrowing and degree of left ventricular dysfunction may explain the similar prognosis for patients with transmural myocardial infarction and those with nontransmural myocardial infarction despite differences in enzymatically estimated acute infarct size.     

Effect of coronary artery recanalization on right ventricular function in patients with acute myocardial infarction

The effects of coronary artery recanalization by intracoronary administration of streptokinase on left ventricular function during acute myocardial infarction have received increasing attention in recent years. Although myocardial dysfunction is often more pronounced in the right ventricle than in the left ventricle in patients with acute inferior wall myocardial infarction, the effect of coronary artery recanalization on right ventricular dysfunction has not been previously addressed. Accordingly, in this investigation, 54 patients who participated in a prospective, controlled, randomized trial of recanalization during acute myocardial infarction were studied. Among 30 patients with inferior wall infarction, 19 had right ventricular dysfunction on admission; 11 of these 19 had positive uptake of technetium-99m pyrophosphate in the right ventricle, indicative of right ventricular infarction. Patients with successful recanalization (n = 6) exhibited improved right ventricular ejection fraction from admission to day 10 (26 +/- 7 to 39 +/- 14%, p less than 0.03). However, control patients (n = 6) and patients who did not undergo recanalization (n = 7) also exhibited improvement (20 +/- 7 to 29 +/- 11% [p less than 0.02] and 30 +/- 8 to 40 +/- 6% [p less than 0.03], respectively). Improvement in several other variables of right ventricular dysfunction evolved at an equal rate with the ejection fraction changes. Patients with or without right ventricular infarction improved similarly. These data indicate that the right ventricular dysfunction commonly associated with inferior wall infarction is often transient, and improvement is the rule, irrespective of early recanalization of the "infarct vessel."     

The importance of the determination of the myocardial area at risk in the evaluation of the outcome of acute myocardial infarction in patients

On the basis of animal studies, we postulated that the size of the perfusion field (risk area) of an occluded coronary artery would be an important determinant of outcome in patients with acute myocardial infarction. To test this hypothesis, we measured size of the risk area in 27 patients with acute myocardial infarction by the intracoronary injection of 99mTc-macroaggregated albumin and gated nuclear imaging. After injection of the albumin spheres (5.3 +/- 1.4 hr after the onset of chest pain) streptokinase was administered and in 16 of 27 patients (59%) effective thrombolysis was achieved. Since none of the patients had evidence of a prior acute myocardial infarction, the 3 day nuclear left ventricular ejection fraction (LVEF) was considered an index of infarct size. Response to thrombolysis was analyzed according to success or failure of reperfusion and the size of the risk area (small risk area less than 25%, large risk area greater than 25% of left ventricular surface area). Standard clinical indexes correlated poorly with size of the risk area: electrocardiographic variables (r = .37), left ventricular end-diastolic pressure (r = .23), cardiac index (r = .55), and the LVEF obtained from a right anterior oblique contrast ventriculogram (r = .31). The coronary vessel responsible for the acute myocardial infarction significantly influenced size of the risk area (left anterior descending, 38 +/- 5% [mean +/- SD] vs circumflex or right coronary artery, 17 +/- 4%). However, knowledge of the site of coronary occlusion within a vessel was not helpful in predicting the size of the area at risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term stepwise sustained improvement in left ventricular ejection fraction after myocardial infarction

Radionuclide left ventricular ejection fraction, end-diastolic volume, and exercise capacity were determined in 34 selected patients who survived a first Q wave anterior infarction. Patients were included in the study if they had no subsequent cardiac events (unstable angina or myocardial infarction) during the average follow-up period of 47 months (range = 36 to 70 months); none was treated with thrombolysis, coronary angioplasty, or bypass grafting. Overall, mean left ventricular ejection fraction increased from 28 +/- 10% 1 month after infarction to 33 +/- 10% at 3 years (p less than 0.01); mean end-diastolic volume decreased from 217 +/- 99 ml to 171 +/- 80 ml (p less than 0.002). Stepwise improvement in left ventricular ejection fraction occurred in 15 of these patients (group B) and was associated with a significant increase in exercise capacity. Mean ejection fraction in group B was 26 +/- 7% at 1 month and 41 +/- 10% at 3 years (p less than 0.001). In all of these patients there was improved regional wall motion in the noninfarct zone, whereas five patients also showed improvement in the infarct zone. The results indicate a progressive improvement in left ventricular function that occurs over time in some patients after first Q wave anterior infarction, independent of intervention.     

Technetium 99m stannous pyrophosphate myocardial imaging in patients with and without left ventricular aneurysm.

To further explore the usefulness of technetium 99m pyrophosphate (99mTc-PYP) myocardial imaging and test its validity in the diagnosis of acute myocardial infarction, 99mTc-PYP myocardial scintigrams were performed in 50 patients. Out of 28 patients with acute myocardial infarction, myocardial scintigrams demonstrated localized activity in the 15 patients with transmural, and diffuse activity in the 13 patients with subendocardial myocardial infarction. Twenty-two patients with significant coronary artery disease documented by coronary angiography but without acute myocardial infarction were also studied. Nine of ten patients with clinical evidence of left ventricular aneurysm from previous myocardial infarction and definite left ventricular dyskinesis had positive scintigrams with activity localized to the site of the wall motion abnormality. Two of five patients without definite aneurysm but with left ventricular akinesis also had localized uptake in the involved area of the left ventricle. Seven patients with normal left ventricular wall motion had negative scintigrams. These findings suggest caution in interpreting positive 99mTc-PYP scintigrams as being indicative of acute myocardial infarction when evidence of a left ventricular aneurysm is also present.     

Intracoronary thrombolysis in acute myocardial infarction: Duration of ischemia as a major determinant of late results after recanalization

To define the effect of duration of myocardial ischemia on the late results after successful thrombolysis in patients with acute transmural myocardial infarction, data on 39 patients treated with intracoronary infusion of streptokinase were analyzed. Patients with successful recanalization of infarct vessel and a time lag between onset of symptoms and reperfusion less than 4 hours were assembled in group A1 (n = 15) and patients with successful recanalization but a time lag of more than 4 hours (n = 17) in group A2. Group B consisted of 7 patients with unsuccessful thrombolysis. Coronary anatomy, left ventricular volume, ejection fraction and regional ejection fraction of infarct area were determined before and 4 weeks after thrombolysis with cineangiography. Serum creatine kinase activity was serially measured.Before intervention, the groups were comparable with regard to age, Killip class, localization of infarction, incidence of previous infarction, Gensini score of coronary anatomy, left ventricular volume, ejection fraction, regional ejection fraction of infarct area and serum creatine kinase activity. Four weeks after the intervention, patients in group A1 had a higher ejection fraction (59 %) and regional ejection fraction of infarct area (39%) than patients in group A2 (ejection fraction: 49%, p < 0.05; regional ejection fraction: 26%, p < 0.05) and group B (ejection fraction: 44%, p < 0.05; regional ejection fraction: 25%, p = 0.05). Peak serum creatine kinase activity measured during the acute illness was lower in group A1 (764 U/liter) than in group A2 (1,580 U/liter, p < 0.05) and group B (2,106 U/liter, p < 0.05).Thus, contraction of infarct area was improved and enzymatic estimate of infarct size was reduced after early as compared with late reperfusion in patients with acute myocardial infarction.     

Scintigraphic evidence that the right ventricular myocardium tolerates ischaemia better than the left ventricular myocardium

To study the incidence of right ventricular infarction and theeffect of intracoronary thrombolysis on the ischaemic rightventricular myocardium, we performed intracoronary myocardialthallium scintigraphy in 18 patients with complete occlusionof the right coronary artery who underwent intracoronary thrombolysis.In 15 of these patients, intracoronary thallium-201 and technetium-99m pyrophosphate scintigrams were performed simultaneously. All18 patients had a right ventricular thallium defect before thrombolysis,and all had new thallium uptake after thrombolysis. 17 out of18 patients had a left ventricular thallium defect before thrombolysis,but only 10 of them showed new thallium uptake after thrombolysis.14 out of 15 patients had a left ventricular technetium-99 mpyrophosphate spot after thrombolysis and some diffuse pyrophosphateaccumulation in the area of the right ventricle. In one patientpyrophosphate accumulation was found only in the area of theright ventricle. Thus, right ventricular thallium defects weredetected by intracoronary thallium scintigraphy in the majorityof patients with inferior acute myocardial infarction due toright coronary artery occlusion. Right ventricular thalliumdefects were always reversible in contrast to left ventricularthallium defects in the same patients, suggesting that rightventricular myocardium tolerates ischaemia better than leftventricular myocardium.     

Use of left ventricular function as an end point of thrombolytic therapy.

In recent acute myocardial infarction, early reperfusion of the infarct-related artery by intracoronary or intravenous thrombolytic therapy induces a significant limitation of infarct size, provided reperfusion occurs within a time frame that myocardial salvage can still be expected. Limitation of infarct size reduces scar tissue formation, aneurysm formation, infarct zone expansion, left ventricular volume enlargement, and eventually results in higher left ventricular ejection fraction. Infarct size limitation and left ventricular function preservation occur with all thrombolytic agents currently in clinical use: streptokinase, alteplase and, more recently, anistreplase. When anistreplase is compared with conventional heparin therapy, a 31% reduction in infarct size is found (estimated from single photon emission computed tomography, or SPECT). This translates into a significant preservation of left ventricular ejection fraction as observed in anistreplase-treated patients compared with heparin-treated patients (0.53 +/- 0.13 vs 0.47 +/- 0.12, p less than 0.002). In comparative trials of 2 thrombolytic agents, anistreplase was demonstrated to be as efficient as alteplase on left ventricular ejection fraction preservation and infarct size limitation.     

Early thrombolysis in acute myocardial infarction: limitation of infarct size and improved survival

The effect of thrombolysis in acute myocardial infarction on infarct size, left ventricular function, clinical course and patient survival was studied in a randomized trial comparing thrombolysis (269 patients) with conventional treatment (264 control patients). All 533 patients were admitted to the coronary care unit within 4 hours after the onset of symptoms related to the infarction. Baseline characteristics were similar in both groups. Informed consent was requested only of patients allocated to thrombolysis; no angiography was performed in 35. The infarct-related artery was patent in 65 patients and occluded in 169. Recanalization was achieved in 133 patients. The median time to angiographic documentation of vessel patency was 200 minutes after the onset of symptoms. The clinical course in the coronary care unit was more favorable after thrombolysis. Infarct size, estimated from myocardial enzyme release, was 30% lower after thrombolysis. In patients admitted within 1 hour after the onset of symptoms the reduction of infarct size was 51%, in those admitted between 1 and 2 hours it was 31% and in those admitted later than 2 hours it was 13%. Left ventricular function measured by radionuclide angiography before hospital discharge was better after thrombolysis (ejection fraction 48 +/- 15%) than in control patients (44 +/- 15%). Similar improvement was observed in patients with a first infarct only (thrombolysis 50 +/- 14%, control subjects 46 +/- 15%), in patients with anterior infarction (thrombolysis 44 +/- 16%, control subjects 35 +/- 14%) and in those with inferior infarction (thrombolysis 52 +/- 12%, control subjects 49 +/- 12%). Similar results were obtained by contrast angiography. Mortality was lower after thrombolysis. After 28 days 16 patients allocated to thrombolysis and 31 control patients had died. One year survival rates were 91 and 84%, respectively. On the other hand, nonfatal reinfarction occurred more frequently after thrombolysis (36 patients) than in control subjects (16 patients). Early thrombolysis by intracoronary streptokinase leads to a smaller infarct size estimated by enzyme release, preserves left ventricular function at the second week and leads to improved 1 year survival.     

Effect of streptokinase on left ventricular modeling and function after myocardial infarction: the GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) Trial

It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic therapy and left ventricular modeling and function after acute myocardial infarction, 331 consecutive patients enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial were studied by two-dimensional echocardiography just before discharge from the hospital. A 6 month follow-up examination was also available in 232 of these patients. Ventricular volumes were computed from an apical four chamber view, according to a previously published algorithm. An infarct size index was also semiquantitatively assessed, according to the number of akinetic and dyskinetic segments in an 11 segment left ventricular model. At predischarge examination, the 161 patients assigned to streptokinase treatment showed smaller ventricular volumes (end-diastolic volume 119.3 +/- 49.7 versus 134.5 +/- 57.8 ml [p = 0.011]; end-systolic volume 65.4 +/- 36.4 versus 74.9 +/- 45.7 ml [p = 0.036]) and smaller regional wall motion index (2.2 +/- 1.9 versus 2.7 +/- 1.9 segments; p = 0.019) compared with values in the 170 patients assigned to standard care; there was no difference in ejection fraction (46.6 +/- 14.1 versus 45.9 +/- 14.9%; p = 0.64). For both groups of patients, there was a significant relation between end-systolic volume and regional wall motion index (p less than 0.001); for large and similar extents of infarct size, ventricular volume was smaller in patients assigned to thrombolytic treatment than in patients assigned to standard care. At 6 months' follow-up, the differences in volume and regional dysfunction detected at the early examination persisted: 110.8 +/- 47.6 versus 127.9 +/- 53.8 ml for end-diastolic volume (p = 0.001), 56.3 +/- 33.6 versus 69.4 +/- 42.1 ml for end-systolic volume (p = 0.001) and 1.8 +/- 1.8 versus 2.3 +/- 1.8 segments for regional wall motion index (p = 0.001). Again, for comparable extents of infarct size, end-systolic volume was smaller in patients who received streptokinase (n = 110) than in those assigned to conventional treatment (n = 122). It is concluded that streptokinase improves left ventricular modeling and function in patients with myocardial infarction, reducing the extent of regional wall motion abnormalities and lessening postinfarction ventricular dilation. The beneficial effects persist up to 6 months.     

Measurement of infarct size using single photon emission computed tomography and technetium-99m pyrophosphate: a description of the method and comparison with patient prognosis

The application of dual tracer transaxial emission computed tomography of the heart was studied with use of technetium-99m pyrophosphate and technetium-99m-labeled red blood cells for measuring infarct size in 20 patients with acute myocardial infarction and 10 without infarction. Imaging was performed with a standard gamma camera and with a multidetector transaxial emission computed tomographic body scanner 3 hours after injection of technetium-99m pyrophosphate. Immediately after the scanning procedure, technetium-99m pertechnetate was injected to label red blood cells, and the scanning protocol was repeated. Technetium-99m pyrophosphate was detected in the anterior wall with involvement of the interventricular septum or lateral wall in patients with electrocardiographic criteria for anterior infarction, whereas uptake was detected in the diaphragmatic left ventricular wall with involvement of the posterior, posteroseptal or posterolateral left ventricle or of the right ventricle in patients with electrocardiographic criteria for inferior or posterior infarction. Infarct size measured from transaxial images ranged from 14.0 to 117.0 g in weight. There was a direct relation between infarct size and patient prognosis in that, of the 13 patients with infarct greater than 40 g, 11 (85 percent) had complications, whereas only 2 (29 percent) of 7 patients with an infarct less than 40 g had complications during a follow-up period averaging 17.8 months (p less than 0.05).     

Quantitative estimation of infarct size by simultaneous dual radionuclide single photon emission computed tomography: comparison with peak serum creatine kinase activity.

To test the hypothesis that simultaneous dual energy single photon emission computed tomography (SPECT) with technetium-99m (99mTc) pyrophosphate and thallium-201 (201TI) can provide an accurate estimate of the size of myocardial infarction and to assess the correlation between infarct size and peak serum creatine kinase activity, 165 patients with acute myocardial infarction underwent SPECT 3.2 +/- 1.3 (SD) days after the onset of acute myocardial infarction. In the present study, the difference in the intensity of 99mTc-pyrophosphate accumulation was assumed to be attributable to difference in the volume of infarcted myocardium, and the infarct volume was corrected by the ratio of the myocardial activity to the osseous activity to quantify the intensity of 99mTc-pyrophosphate accumulation. The correlation of measured infarct volume with peak serum creatine kinase activity was significant (r = 0.60, p less than 0.01). There was also a significant linear correlation between the corrected infarct volume and peak serum creatine kinase activity (r = 0.71, p less than 0.01). Subgroup analysis showed a high correlation between corrected volume and peak creatine kinase activity in patients with anterior infarctions (r = 0.75, p less than 0.01) but a poor correlation in patients with inferior or posterior infarctions (r = 0.50, p less than 0.01). In both the early reperfusion and the no reperfusion groups, a good correlation was found between corrected infarct volume and peak serum creatine kinase activity (r = 0.76 and r = 0.76, respectively; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute coronary artery obstruction in myocardial infarction: overview of thrombolytic therapy

Pump failure, ranging from ventricular dysfunction to acute cardiogenic shock, is now the leading cause of cardiac death. Efforts at temporary mechanical or pharmacologic support of the heart have been largely unsuccessful so that attention is now directed toward prevention of ventricular failure and limitation of myocardial infarct size or even outright prevention of infarction itself. In particular, attention has been refocused on earlier reperfusion efforts with streptokinase. The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function and early mortality was studied in subsets of patients in a randomized trial (Netherlands Interuniversity Cardiology Institute). Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared with conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. Of the patients eligible for this detailed analysis, 245 were allocated to thrombolytic therapy and 243 to conventional treatment. Early angiography was preformed in 212 of the 245 patients allocated to thrombolytic therapy. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size, measured from cumulative alpha-hydroxybutyrate dehydrogenase release, was smaller in patients allocated to thrombolytic therapy (median 760 versus 1,179 U/liter in control subjects, p = 0.0001). Left ventricular ejection fraction measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% versus 43% in control subjects, p = 0.0001). Twelve month mortality was lower in patients allocated to thrombolytic therapy (8% versus 16% in the control group, p less than 0.01). In multivariate regression analysis infarct size limitation, improvement of left ventricular ejection fraction and 3 month mortality were predicted by sigma ST, time from onset of symptoms to admission and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with a sigma ST segment of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function or mortality were observed in the subset of patients with sigma ST less than 1.2 mV, admitted 2 to 4 hours after onset of symptoms.