Influence of baseline ejection fraction and success of thrombolysis on mortality and ventricular function after acute myocardial infarction

OCTOBER 1, 1984

The American

, J o u r n a l of C A R D I O L O G Y " VOLUME 54 NUMBER 7

CORONARY HEART DISEASE

Influence of Baseline Ejection FractiOn and Success of Thrombolysis on Mortality and Ventricular Function After Acute Myocardial Infarction DAVID W. FERGUSON, MD, CARL W. WHITE, MD, JOHN L. SCHWARTZ, MD, GAlL P. BRAYDEN, MD, KEVIN J. KELLY, MD, J. MICHAEL KIOSCHOS, MD, PETER T. KIRCHNER, MD, and MELVIN L. MARCUS, MD

The efficacy of streptokinase (STK) thrombolytic therapy was prospectively evaluated in 77 consecutive patients presenting within 9 hours of onset of acute myocardial infarction. Serial left ventricular (LV) ejection fraction (EF) was assessed by radionuclide ventriculography, initially (acute) and at 1 month (late). The role of initial LVEF was examined by comparing patients with an acute LVEF

EF = 56 -I- 2 % (mean -I- standard error of the mean), late EF = 55 -I- 2 % (p = not significant INS]); group IBmacute EF = 58 4- 1 % , late EF = 55 :E 2 % (NS); group IIAmacute EF = 35 -I- 2 % , late EF = 4 -I- 4%, (NS); group II B ~ a c u t e EF = 36 4- 2 % , late EF = 41 4- 3 % (NS). No patient with an acute EF > 5 0 % died, i.e.,,group IA patients (n = 7) or group IB patients (n = 13). However, there was a significant difference in the mortality rate between patients with an acute EF < 5 0 % who had successful persistent thrombolysis and those in whom thrombolysis failed (groups IIA and liB: mortality group IIA = 1 of 20 (5 % ) and mortality group liB = 11 of 25 ( 4 4 % ) , p = 0.003 group IIA vs liB), with 9 2 % of all deaths occurring in patients with anterior myocardial infarction. Thus, the primary demonstrable benefit of STK thrombolysis is a lower mortality rate among patients with an initial LVEF < 5 0 % .

> 5 0 % (type I) with those with LVEF <50% (type II). Sixty-five patients (84%) had total coronary occlusion and received STK. Initial successful reperfusion was achieved in 34 patients (52%), but repeat angiograms at 10 to 14 days revealed persistent patency in only 27 patients. Within the type I and type II classification, 2 patient subgroups were compared: Group A had successful and persistent thrombolysis and group B had initial failure of thrombolysis or in-hospital reocclusion. There was no significant change in global LVEF in any group from acute to 1 month follow-up: group IA~acute

(Am J Cardiol 1984;54:705-711)

Recent studies in man have demonstrated the important role of coronary thrombosis in the pathogenesis of

acute myocardial infarction (AMI). The use of surgical and medical therapy (i.e., thrombolysis) to achieve reperfusion has been reported in a number of early studies, 1-1° but the efficacy of these interventions is not known. 11-12The advisability of widespread application of this technique thus remains questionable, la Experimental studies in animals have suggested that reperfusion limits the extent of myocardial necrosis during the early stages of experimental infarction. 14-23The role of time to reperfusion in human infarctions is an unclear predictor of o u t c o m e . 24-26 In this study, we report our experience with 77 consecutive patients who underwent interventional evaluation for transmural AMI. We have assessed the effects of successful streptokinase (STK)

From the Cardiovascularand Clinical Research Centers and Department of Internal Medicine, University of Iowa College of Medicine, University of Iowa Hospitals and the Veterans Adminisb'ationMedical Center, Iowa City, Iowa. This study was supported in part by Grant HL14380 from the National Heart, Lung, and Blood Institute and General Clinical Research Grant RR-59 from the National Institutes of Health, Bethesda, Maryland, and a grant-in-aid from the Iowa Affiliate of the American Heart Association, West Des Moines, Iowa. Manuscript received February 13, 1984; revised manuscript received May 31, 1984, accepted June 5, 1984. Address for reprints: David W. Ferguson, MD, Medical Center Hospital of Vermont, Division of Cardiology, Burlington, Vermont 05401. 705

706

STREPTOKINASE THROMBOLYSIS

FOR ACUTE INFARCTION

r e p e r f u s i o n on global left v e n t r i c u l a r (LV) ejection fraction (EF) and s h o r t - t e r m hospital m o r t a l i t y a n d have e x a m i n e d the i m p o r t a n c e of t i m e to reperfusion as a d e t e r m i n a n t of outcome. Methods

Patients: This study comprises 77 consecutive patients seen at the University of Iowa Hospital from November 1981 through March 1983, who presented within the first 9 hours after the clinical onset of an AMI. Criteria for admission to the study were: (1) history of prolonged chest pain (longer than 20 minutes) and symptoms consistent with AMI; (2) onset of chest pain within 9 hours preceding arrival in the cardiac catheterization laboratory; (3) age younger than 80 years; (4) no history or evidence of AMI in the region involved with the acute event; (5) electrocardiographic findings suggestive of a transmural AMI, defined as at least 2 mm of ST-segment elevation (20 ms after the J point) in 2 or more leads reflecting the infarcting wall (inferior leads--II, III and aVF; anterior leads--I, aVL and V1-V6); (6) persistence of ST-segment elevation after administration of sublingual nitroglycerin, 0.4 mg; and (7) no recent (within 14 days) history of cerebrovascular accident, major trauma or surgical procedure. All patients gave informed, written consent. The study protocol was approved by the Human Subjects Review Committee of the University of Iowa. No patient was excluded because of hemodynamic instability. Patient subgroups: Patient subgroups were defined on the basis of coronary artery perfusion status and baseline LV function as assessed by radionuclide ventriculography. Patients with an initial acute LVEF >50% were defined as type I and those with an acute LVEF ,(50% were type II. Within this classification, 2 patient subgroups were compared: Group A had successful and persistent thrombolysis and group B had either initial failure of thrombolysis or reocclusion of the involved coronary artery documented during the acute hospitalization. Protocol: Of the 77 patients who met the study criteria, 37 were transferred by University of Iowa Air Care Emergency Helicopter ambulance and 7 patients by ground ambulance from outlying emergency rooms 30 to 120 miles from the University of Iowa Hospitals. All patients were receiving prophylactic lidocaine (1- to 2-mg/kg bolus, followed by a continuous infusion at 2 to 4 mg/min) and, if hemodynamically stable, the patients were premedicated with Benadryl ®, 50 mg intravenously, and Phenergan ®,25 mg subcutaneously. The patients were given sublingual nitroglycerin and intra-

77 Patients with Acute MI J Non-total Coronary Occlusion Acutely N= 12 Total Thrombotic Coronary Occlusion Acutely N=65

I

I

Initially Successful STK Thrombolysia N - - 3 4 ~

I

J Persistent Coronary Patency N=27 (Group A) I

I

Acute LVEF_P 50% N=7

(Type

I-A)

I

Initial Failure of STK Thrombolysis N=31

~,n-hospital Coronary J Re-occlusion N=7 Persistent Total ~ C o r o n a r y Occlusion N=38 (Group B) I

I

I

Acute LVEF < 50% N=20

Acute LVEF.2- 50% N= 13

Acute LVEF = 50% N=25

(Type II-A)

(Type I-B)

(Type II-B)

FIGURE 1. Clinical course of patients undergoing intracoronary streptokinase (STK) therapy during acute myocardial infarction (MI). Subgroup definition is based on acute left ventricular ejection fraction (LVEF) and coronary patency.

venous morphine sulfate in increments of 2 to 4 mg as pain and hemodynamics dictated. All patients underwent invasive study within 9 hours of the onset of their prolonged chest pain. Acute cardiac catheterization: Using the percutaneous femoral Seldinger approach, the following studies were performed in the order indicated after the initial bolus of heparin, 5,000 U intravenously: (1) Assessment of systemic arterial and LV pressures. (2) LV cineangiography in the 45 ° right anterior oblique projection (omitted if LV end-diastolic pressure was greater than 35 mm Hg or if the patient was hemodynamically unstable. (3) Selective coronary arteriography of both left and right coronary systems performed in at least 2 orthogonal projections each. (4) If total coronary occlusion was identified in the vessel supplying the infarcting region, sublingual nifedipine, 10 mg, and intracoronary nitroglycerin, 300 to 400 ~tg, was administered and coronary arteriography repeated in 1 to 2 minutes to exclude the possibility of coronary artery spasm. (5) If total coronary occlusion persisted, the patients were then given 10,000 to 20,000 U of intracoronary streptokinase (Streptase ®, Hoechst-Roussel) as a bolus followed by continuous intracoronary infusion at 2,000 U/min with an infusion pump. (6) Right-sided cardiac catheterization and measurement of thermodilution cardiac output was performed immediately after STK was started. (7) Repeat coronary arteriogram of the involved coronary artery was repeated every 15 minutes, or sooner if symptoms or electrocardiographic changes suggested reperfusion. Streptokinase was infused for at least 45 minutes in all patients, with the goal of 30 minutes or more of infusion after initial reperfusion or until 90 minutes of total infusion time. Repeat boluses of 10,000 to 20,000 U of STK were administered every 15 minutes if reperfusion did not occur. The total time of STK infusion was usually 60 to 90 minutes (range 45 to 135). Therapy after catheterization: After the acute study, all patients were admitted to the Cardiovascular Intensive Care Unit with invasive hemodynamic monitoring maintained for at least 18 hours. Full-dose intravenous heparin therapy was continued immediately after the acute catheterization until repeat study in 10 to 14 days to achieve a therapeutic state of anticoagulation, defined as a partial thromboplastin time longer than 60 seconds only in those patients with initial total thrombotic occlusion in whom successful reperfusion was achieved with STK. All patients were given topical, oral or intravenous nitrates, and nifedipine, 10 to 20 mg orally every 8 hours. If the cardiac index was >2.5 liters/min/m 2 and pulmonary capillary wedge pressure <18 mm Hg, oral propranolol was initiated at a dose of 10 to 20 mg orally every 6 hours. Congestive heart failure, cardiogenic shock and mechanical complications were managed with vasodilators, vasopressors and, in some cases intraaortic balloon counterpulsation. Medical therapy after discharge from intensive care (usually 72 hours later) was individualized by the patient's physician. Serial assessment of left ventricular ejection fraction: Immediately on arrival in the intensive care unit, global LVEF was assessed by radionuclide ventriculography (acute study). Two follow-up radionuclide ventriculograms were obtained, 1 at 3.2 4- 0.2 days (early study) and 1 at 31 4- 1 days (late study). Gated resting radionuclide ventriculograms were obtained using in vivo labeling of red blood cells with technetium-99m using standard techniques. Follow-up cardiac catheterization: All patients who achieved initial successful thrombolysis and survived were restudied angiographically at 10 tO 14 days to assess the state of coronary perfusion, total extent of coronary artery disease and LV function as a guide to further therapy (i.e., medical vs surgical therapy).

707

October 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54

TABLE I

Baseline Clinical and Hemodynamic Characteristics of Patient Subgroups . Group IA

Clinical characteristics Total no. Sex (% male) Age (yr) Anglo time (hr,.) STK dose (10~U) STK time (min) Acute infarct type Anterior (no.) Inferior (no.) Remote infarct (no.) Hemodynamic characteristics HR (beats/min) MAP (mm Hg) CI (liters/min/m 2) SV (ml/min) LVEDP (mm Hg) MPAP (mm Hg)

Group IB

Group IIA

Group liB

p Value

7 71% 45 4- 5 6.0 4- 0.7 109 4- 19 69 4- 6

13 85% 58 -1- 3 5.1 -I- 0.4 228 4- 23 75 4- 6

20 75% 53 -I- 2 5.3 4- 0.3 203 4- 17 69 4- 5

25 88% 55 -I- 2 5.2 -t- 0.4 208 4- 11 71 4- 5

NS NS NS NS NS

1 6 0

2 11 1

14 6 4

16 9 0

° ° NS

77 99 3.1 76 18 23

444444-

4 4 0.3 7 2 1

71 90 3.1 78 18 20

444444-

3 5 0.2 7 2 2

83 86 2.8 66 23 25

444444-

4 4 0.1 4 2 2

86 89 2.8 68 23 24

444444-

5 4 0.1 5 2 1

NS NS NS NS NS NS

Values are mean 4- standard error of the mean. * p <0.05 for anterior vs inferior infarction for each patient subgroup. Angio time = time from onset of chest pain to acute angiographic study; CI = cardiac index; HR = heart rate; LVEDP = left ventricular end-diastolic pressure; MAP = mean arterial pressure; MPAP = mean pulmonary artery pressure; NS = not significant; STK = streptokinase; STK time = time of STK administration; SV = stroke volume. See text for group definitions.

Statistical analysis: Data are presented in the text and figures as mean ± standard error of the mean. Intergroup comparisons were performed by 2-way analysis of variance. Nonparametric comparisons between groups were performed by chi-square analysis. Statistical significance was defined at p <0.05.

TABLE II

Group

Acute LVEF (%)

Early LVEF (%)

Late LVEF (%)

p Value

Group I (Acute LVEF > 5 0 % )

Results

Patient subgroup definition: Figure 1 shows the breakdown of patient groups. Of the patients with successful and persistent S T K thrombolysis, 7 had an acute LVEF >_50% as determined by radionuclide ventriculography (group IA) and 20 patients had an acute LVEF <50% (group IIA). Of the patients with persistent total coronary occlusion due either to failure of thrombolysis or to in-hospital reocclusion, 13 had an acute LVEF >_50% (group IB) and 25 had an acute LVEF <50% (group IIB). Characteristics of patient subgroups: The demographic, clinical and hemodynamic characteristics of the 4 patient subgroups are summarized in Table I. The 4 groups had comparable clinical and demographic characteristics. Groups IA and IB (LVEF >_50%) had predominantly inferior AMI and groups IIA and IIB (LVEF <50%) had predominantly anterior AMI. The 4 patient subgroups had comparable baseline hemodynamic values, including heart rate, mean arterial pressure, cardiac index, stroke volume, LV end-diastolic pressure and mean pulmonary artery pressure. All groups had comparable elevations in LV end-diastolic pressure. Serial left v e n t r i c u l a r ejection fraction: Table II is a summary of the serial LVEF data as assessed by radionuclide ventriculography. Patients in groups IA and IB had comparable acute LVEF. Serial radionuclide ventriculograms were performed in all patients in groups IA and IB and showed no significant change in LVEF from acute to early (3 days) or late (1 month) studies. Similarly, baseline acute LVEF was similar in

Serial Left Ventricular Ejection Fraction of Patient Subgroups as Assessed by Radionucllde Ventriculography

IA IB

56 -I- 2 58 4- 1

59 -I- 3 60 -I- 2

55 -I- 2 55 -I- 2

NS NS

Group II (Acute LVEF < 5 0 % ) IIA liB

35 -I- 2 36 -I- 9

42 4- 3 41 4- 3

40 -1- 4 41 -F 3

NS NS

Values are mean 4- standard error of the mean. LVEF = left ventricular ejection fraction; NS = not significant. See text for group definitions.

groups IIA and IIB. In group IIA, all 20 patients had acute ventriculograms, but 1 patient died before the early study (n = 19) and 2 patients did not have a late study performed for technical reasons (n - 17). There was no significant change in serial LVEF in group IIA or IIB patients. Of the 25 group IIB patients, 6 died within several hours of admission; an acute radionuclide ventriculogram was therefore only obtained in 19 patients. Four other patients died before the early study. The eleventh death in this group occurred before hospital discharge and 1 survivor failed to have a late lomonth study, yielding a total of 13 patients in group IIB. Figure 2 shows the marked variability in global LVEF as assessed by radionuclide ventriculography in patients who presented with an acute LVEF <50%. Although baseline acute LVEF was similar in both patients with successful persistent thrombolysis (group IIA) and those with persistent total occlusion (group IIB), there was a great deal of individual variation in serial measurements of LVEF. The overall responses between these

708

STREPTOKINASETHROMBOLYSIS FOR ACUTE INFARCTION

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2 groups in global LVEF were not significantly different. Effects of in-hospital reocclusion: Of the 34 patients who initially achieved successful STK thrombolysis (Fig. 1), 7 had clinical, angiographic or autopsy confirmation of reocclusion of the involved coronary artery within 12 days of the acute thrombolysis. The clinical characteristics and functional results of this reocclusion are summarized in Table III. All patients had a prolonged episode of anginal chest pain, occurring from 12 hours to 12 days after initial thrombolysis and clinically consistent with reocclusion. Reocclusion of the previously opened coronary artery was confirmed angiographically in 5 patients and at postmortem examination in i patient. The seventh patient had recurrent chest pain with acute reelevation of ST segments in the inferior wall leads 2 days after initial reperfusion of an

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I I Acute 1 Month Acute 1 Month FIGURE 2. Changes in global left ventricular ejection fraction (LVEF) from acute to 1-month study in patient subgroups as assessed by radionuclide venb'iculography. There was a great deal of variability in LVEF in both patients with successful and persistent reperfusion (GROUP II-/%) and those with failure of thrombolysis initially or in-hospital reocclusion (GROUP II-B). Overall responses between the 2 groups were not different. -40

l

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I-B II-A Patient Groups

Coronary Coronary Patent Occludedl Acute LVEF >_ 5 0 %

II-B

Coronary Coronary I Patent Occluded I Acute LVEF < 5 0 %

FIGURE 3. In-hospital mortality rate in patient subgroups. There were no deaths among the patients with a left ventricular ejection fraction (LVEF) > 50 % (groups I-A and I-B). There was a significant reduction in mortality in group II-A (mortality 5 % ) patients who had successful and persistent reperfusion as compared with group II-B patients (mortality 44%), who had initial failure of reperfusion or in-hospital coronary reocclusion. " p <0.01 for mortality in group II-B vs other groups.

Ootober 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54

occluded right coronary artery. The onset of pain was followed rapidly by hypotension and death. Reocclusion was clinically correlated with rapid development of cardiogenic shock and death in 3 patients and enzymatic confirmation of infarct extension in 1 patient. I n - h o s p i t a l mortality: In our 77 patients, the overall in-hospital mortality was 16%. The mortality data are summarized in Figure 3 and Table IV. There were no hospital deaths among the patients whose initial LVEF was >50%, regardless of success or failure of initial STK thrombolysis (groups IA and IB). One of the 20 patients in group IIA died (5% mortality rate), a significantly lower rate than that among the 25 patients in group IIB (11 deaths, mortality rate 44%) (p <0.01 vs group IIA). Ninety-two percent of the deaths occurred in patients with anterior AMI. Only 1 of the 14 patients with anterior AMI in group IIA died, compared with 10 of the 16 patients with anterior AMI in group IIB (p <0.05). Only 25% of the patients who subsequently died were in Killip class III to IV on arrival. In two-thirds of the patients who died, STK thrombolysis was initially unsuccessful, and in an additional 25% rethrombosis followed initial successful thrombolysis. One patient had initial successful thrombolysis and died 12 hours late~" of LV free wall rupture without a clinical suspicion of rethrombosis. All patients died as a result of cardiogenic shock with or without a mechanical lesion (1 as a result of ventricular septal defect and 2 from LV free wall rupture) or severe refractory congestive heart failure. There were no primary arrhythmic deaths. Three patients died during the acute cardiac catheterization. All 3 were in cardiogenic shock on or shortly after arrival in the catheterization laboratory; catheterization was performed during cardiopulmonary resuscitation in 2 and attempted thrombolysis was unsuccessful in all 3. There were an additional 8 early deaths (within 72 hours) and 1 "late" hospital death. Influence o f time on s u c c e s s of thrombolysis: The influence of time from onset of chest pain to acute an-

T A B L E IV

709

S u m m a r y of Patient D e a t h s During A c u t e H o s p i t a l i z a t i o n (n = 1 2 )

Clinical characteristics Sex: Male (%) Age (yr, mean 4- SEM) Infarct type: Anterior (LAD) Inferior (RCA) Admission Killip class: I II III IV Angiographic characteristics Total CAD 1 vessel 2 vessel 3 vessel Results of STK thrombolysis Initial failure to reperfuse Initial STK reperfusion-rethrombosis Initial STK reperfusion-unknown if rethrombosis Primary cause of death Cardiogenic shock without mechanical lesion Cardiogenic shock with acute VSD LV free wall rupture Progressive CHF Time of death after acute infarct During acute cardiac catheterization Acute periinfarct period (<72 hours) "Late" hospital death (3-15 days)

10 57 4- 2 11 1 7 2 1 2 2 5 5 8 3 1 8 1 2 1 3 8 1

CAD = coronary artery disease; CHF = congestive heart failure; LAD = left anterior descending coronary artery; LV = left ventricular; RCA = right coronary artery; SEM = standard error of the mean; STK = streptokinase; VSD = ventricular septal defect,

giographic study on the change in LVEF after successful thrombolysis is summarized in Figure 4. Most patients were studied angiographically between 4 and 7 hours. There was no significant correlation between time to angiographic study and reperfusion and change in LVEF (r = -0.10, p = 0.61). The ability to achieve successful thrombolysis did not appear to be a timerelated phenomenon (Fig. 5). Most patients were studied from 3 to 6 and 6 to 9 hours after onset of symptoms, with approximately the same success rate

30

50

uccessful )mbolysis

20

40

)rnbolysls

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II Coronary n

& LVEF 10 from Acute 0 to Late (units) -10 -20 -30

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go °

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•

I o

•

I o •

I 9.0

o••

• Persistent Coronary Patency o Re-Occlusion r = -0.10 p-- 0.61 Time to Angiographic Study (hrs)

FIGURE 4. Influence of time from onset of chest pain to acute interventional study on the change in left ventricular ejection fraction (~.LVEF) from acute to I month (late) study. Data are presented for all patients with initial successful reperfusion, including those with persistent patency and those who subsequently had reocclusion of the involved vessel. There was no significant correlation between time and change in LVEF.

Number of Patients

30 20 10 O

0-3 hrs. 3-6 hrs. 6-9 hrs. Time from Symptoms to Angiography

FIGURE 5, Influence of time from onset of chest pain to acute interventional study on presence of total thrombotic coronary occlusion and initial success of thrombolysis. Patients with nontotal occlusion, those with initial success of streptokinase (STK) thrombolysis and those with initial failure to achieve STK thrombolysis were seen throughout the 9-hour study period. Time to presentation and interventional study did not appear to be a critical factor determining presence of total thrombotic occlusion or success of attempt at STK reperfusion.

710

STREPTOKINASETHROMBOLYSIS FOR ACUTE INFARCTION

for initial thrombolysis in these 2 time periods. Similarly, patients with nontotal occlusion were seen throughout the 9-hour period of the study. Discussion

Five conclusions may be drawn from this study. First, a significant reduction in in-hospital mortality appeared to exist in patients with successful and persistent reperfusion of the infarcting coronary bed that primarily involved anterior AMIs. Second, in-hospital reocclusion of an initial successfully reperfused vessel was frequently associated with serious consequences. Third, the time from onset of symptoms to acute intervention within the time frame we examined (0 to 9 hours) did not appear to be a critical determinant of the success of reperfusion or change in global LVEF after intervention. Fourth, no significant benefit of reperfusion was observed in patients who presented initially with LVEF >50%. Finally, there was a heterogenous response in all patient subgroups with reference to changes in global LVEF, such that no significant change in global LVEF could be documented regardless of the success or failure of reperfusion. The discussion will focus on comparison of this study with those previously described, the role of time as a factor in the reperfusion equation and the use of global LVEF as an index of improvement after reperfusion for AMI. Comparison w i t h r e c e n t studies: We found a significant reduction in hospital mortality in patients with an initial LVEF <50% who had successful reperfusion compared with those in whom reperfusion failed or who initially underwent reperfusion and had subsequent reocclusion. This finding was essentially limited to patients with anterior wall AMI. Similar findings with respect to mortality have been reported by other investigators. 26,27 We specifically examined the potential benefit of STK thrombolysis in patients presenting initially with a normal LVEF >50% (groups IA and IB) and in those presenting with depressed LVEF <50%, (groups IIA and IIB). We hypothesized that in patients who present with normal LVEF, we would be unlikely to find a significant improvement in global LVEF. The majority of patients with acute LVEF >50% had sustained inferior wall infarctions (Table I). Previous investigators have reported that patients with inferior infarctions are a low-risk g r o u p ; 28 thus, any intervention would be unlikely to provide substantial improvement in mortality. The reverse would appear true for patients with acute LVEF <50%, two-thirds of whom had sustained anterior infarctions, a subgroup with a less favorable acute prognosis. 28 It was in these patients that STK reperfusion in our study appeared to offer significant benefit. The success rate of initial reperfusion of a totally occluded coronary artery in this study was 52%, a value somewhat lower than the 60 to 100% success rate reported in many recent series. 1-12,25-27 The reasons for this are unclear. Our dose of STK and mode of its administration were similar to those reported elsewhere. In almost all cases we performed infusion using a routine angiographic catheter placed in the ostium of the cor-

onary vessel supplying the infarct zone. After several unsuccessful uses of a subsetective catheter, we abandoned the subselective technique. This experience is similar to that of other investigators. 26 We found an unexpectedly high rate (21%) of confirmed reocclusion in this study. Reocclusion occurred in most of these patients within 48 hours and was associated with significant sequelae (Table III). Gold et a129 reported angiographic confirmation of acute reocclusion within 2 hours of successful thrombolysis in 6 of 34 patients and an additional 5 patients had late reocclusion, yielding a total reocclusion rate of 11 of 34 patients (32%). Our protocol is to maintain full dose intravenous heparin anticoagulation in all patients who initially undergo reperfusion with STK. The risk of reocclusion in our patients is likely related to severe residual coronary artery stenosis as reported by Harrison et al. 3° T i m e as f a c t o r in success of r e p e r f u s i o n : Experimental studies in animals originally suggested that reperfusion limits the extent of myocardial necrosis during the first 3 to 4 hours of an acute infarction. 14-23 Preliminary studies in man have also suggested that for reperfusion to be effective, it must be accomplished within the first few hours after the onset of infarction. 24,25 However, the concept has recently been disputed. 26 Consequently, the importance of time to reperfusion as a factor determining outcome in clinical reperfusion trials in humans is unclear. We have analyzed the role of time in regard to ability to achieve initial successful reperfusion and the effects of time-related reperfusion on serial assessment of global LVEF. The mean time of angiographic study was 5.4 hours, with 7 patients (9%) presenting within 3 hours, 46 (60%) presenting within 3 to 6 hours, and 24 patients (31%) presenting from 6 to 9 hours. Reperfusion was initially successful in 57% of those who presented early (0 to 3 hours), in 37% of those presenting from 3 to 6 hours and in 54% of those presenting from 6 to 9 hours. Thus, time to presentation and interventional study did not appear to be a critical factor in determining success of reperfusion. However, because we could only study 9 patients within 3 hours of onset of infarction, conclusions regarding the influence of time to reperfusion during the early hours of infarction cannot be definitely made. Similarly, the change in EF after successful reperfusion did not at all correlate with time from onset of symptoms to time of intervention. Similar findings have been reported by Smalling et al, 26 who found significant improvement in LV function with reperfusion up to 18 hours after the clinical onset of infarction. Global v e n t r i c u l a r f u n c t i o n a f t e r a c u t e i n f a r c tion: The patients in our study showed no significant improvement in global LVEF regardless of the success or failure of reperfusion. The likely reasons for this finding include the heterogeneity of ventricular function after acute infarction and the role of segmental hyperfunction of the noninfarcting ventricular wall. Regional hyperfunction of the noninfarcting myocardial segment may be present initially but not in follow-up studies, 1° falsely elevating the initial overall assessment of global

October 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 54

LVEF. The natural history of ventricular function after AMI in humans is known to be variable. Apparent spontaneous variability in LVEF occurs in up to 56% of patients evaluated serially within the first 24 hours of AMI in the absence of any specific intervention. 31 The factors in this variability remain uncertain. Therefore, the assessment of LV function by measurements of L V E F is probably a poor predictor of myocardial salvage after AMI. Acknowledgment: We thank Jill Christy for help in preparation of the manuscript and Tom O'Gorman for assistance in statistical analysis. We also express our sincere appreciation to the attending and housestaff physicians at the University of Iowa and to the local referring physicians for allowing us to study patients under their care.

13. 14.

15.

16.

17. 18.

19.

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