Percutaneous Transluminal Coronary Angibplasty After lntracoronary Streptokinase in Evolving

Acute Myocal’dial Infarction

SILVIO E. PAPAPIETRO, MD, WILLIAM A. H. MacLEAN, filD,

ALFRED W. H. STANLEY, Jr., MD, RANDALL G. HESS, DO,

NAN CORLEY, MD, JOAQUIN G. ARClhilEGAS, MD,

and TERRY B. COOPER, MD

To achieve optimal inyocardial revasculariiation and prevent rethrombosis of the infarct-related coronary artery, percutaneous transluminal coronary angioplasty (PTCA) was attempted in 18 patients with evolvin$ acute myocardial infarction (9 anterior and 9 inferior) after administration of intracoronary streptoklnase. PTCA was attempted 338 $Z 151 minutes after the onset of symptoms. After throm- bolytic therapy, 11 patients had a severe residual stenosis and 7 a persistent total occlusion of the infarct-related coronary artery. PTCA was suc- cessful in 13 of 18 patients: in ? of 11 with coronary stenoses and in 4 of 7 with total coronary oc&lusions. PTCA reduced the severity of the coronary lesion from 91 f 2% to 27 f 7% (p <O.OOl), and the transstenotic pressure gradient from 38 f 5 to 6 f

2 mm Hg (p <O.Ol). One patient in cardiogenic shock died during urgent coyoqary surgery after unsuccessful PTCA. After PTCA, all patients re- ceived heparin arid antiplatelet agents. One patient had reinfarction with reocclusion of the infarct-re- lated artery 5 days after PTCA. The’other 12 patients had an uneveritful hospital course, and carlliac catheterization before hospital discharge (8 to 17 days) revealed reocclusion of the infarct-related coronary artery in 3 and p&sistent patency in 9. Persistent patency of the infarct-related artery was associated with preservation of left ventricular end-diastolic volume (initial 86 k 6 ml/m*, follow-up 9 1 f 6 ml/m*), and improvement in left ventricular ejection fraction in some patients.

(Am J Cardiol 1985;55:48-53)

Thrombolysis with streptokinase (STK) early after the onset of acute myocardial infarction (AMI) frequently results in reestablishment of blood flow in thrombosed coronary arteries. 1-3 After thrombolysis, residual ste- noses usually remain at the site of initial occlusion, and may result in incomplete revascularization and re- thrombosis.2*4,5 Anticoagulant and antiplatelet agents have been used to prevent rethrombosis, with variable success.Z-5 Cdrohary artery bypass surgery and percu- taneous transluminal coronary angioplasty (PTCA) have been used immediately after or several days after thrombolysis to prevent reocclusion and achieve com-

From the Division of Cardiology, Department of Medicine, Carraway Methodist Medical Center, and Norwood Clinic, Birmingham, Alabama. This study was supported by the Kemp-Carraway Heart Institute, Bir- mingham, Alabama. Manuscript received June 18, 1984; revised manuscript received August 29, 1984, accepted August 31, 1984.

Address for reprints: Silvio E. Papapietro, MD, Division of Cardiology, Carraway Methodist Medical Center, 1600 North 26th Street, Bir- mingham, Alabama 35234.

plete revascularization.2-4 In this study, we report our experience with 18 patients with evolving transmural AM1 in whom PTCA was attempted immediately after intracoronary STK treatment.

Methods Patients: From October 1981, through December l&32,83

patients with an eirolving transmural AM1 underweht cardiac catheterization and received intracoroniry STK within 12 hours from onset of symptoms. The diagnosis of AMI was established by a history of chest pain, associated with mbrti than 1.5 mm of ST-segment elevation in 2 or moie electro- cardiographic leads. Patients gave informed consent for car- diac catheterization, thrombolysis and PTCA. Aft& admin- istration of intracoronary STK, 18 patients (Table I) were selected for PTCA. They represent consecutive PTCA at- tempts, and were considered candidates for PTCA because after STK, they had a persistent occlusion or a severe stenosis in the infarct-related artery, jeopardizing a large segment bf myocardium. The coronary lesion was believed suitable for

January 1, 1985 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 55 49

TABLE I Clinical Characteristics of Patients

Time from Onset of

initial Symptoms Age W Previous Location LVEDP Initial Cl to PTCA Extent

Pt & Sex MI of AMI (mm Hg) (I/min/m*) (min) of CAD

1 43M No0 Inf 15 i .a5 350 3 50M 57M No No 0 0 Ant Inf $8 3.29 2.73 185 135 iv”

4 63F No0 Inf 20 2.57 502 K

: 67F 41M No0 No 0 Ant Inf 27 3.63 1.85 304 508 x;

3 54F 54F No0 No0 Ant Inf ;5” 16 3.75 3.12 245 341 %:: 1: 71M 46M No0 No 0 Ant Inf 1: 3.27 2.20 285 755 3v

:: 33M 55M No No 0 0 Ant Inf 46 3.96 3.20 413 427 :::

:: 62M 37M No No 0 0 Ant It-if :s 20 2.18 265 127 :; 1v

15 49M No 0 Ant 15 iii 389 :7” 46M 45M Yes No0 + Ant Inf :: 2.56 3.37 215 210

iv” 2v

18 59M No0 Ant 30 3.39 419 IV

AMI = acute myocardial infarction; Ant = anterior; CAD = coronary artery disease; Cl = cardiac index; Inf = inferior; LVEDP = left ventricular enddiastolic pressure; PTCA = percutaneous transluminal coronary angioplasty; V = vessel; + = present; 0 = absent.

PTCA based.on its proximity to the ostium of the artery, type (discrete, concentric, noncalcified), presence and extent of residual thrombus and experience of the operator.

Cardiac catheterization: After initial evaluation, the 18 patients underwent cardiac catheterization (femoral ap- proach). Cardiac output was determined by thermodilution. Biplane left ventricular angiography (30’ right anterior oblique/l5” cranial-60° left anterior oblique) was performed using 36 ml of diatrizoate meglumine injected over 3 seconds. Coronary angiography was performed in multiple views, and was performed first in the artery suspected not to be respon- sible for the AMI. Complete occlusion of the infarct-related artery was found in 16 patients and severe subtotal occlusion with nonocclusive thrombus was found in 2 (Table II).

Streptokinase: Patients received heparin, 10,000 IU, di- phenhydramine hydrochloride, 50 mg, and methylpredniso- lone, 1.0 g intravenously, and nitroglycerin, 100 to 250 pg into the ostium of the infarct-related artery (left main or right coronary artery). No improvement in flow was observed after nitroglycerin. Subsequently, STK (Streptase,@ Hoechst) 250,000 IU in 250 ml of 0.9 M sodium chloride, was adminis- tered as a 20,000-IU bolus in the infarct-related artery, and followed by an infusion of 4,000 or 3,000 IU/min, until the ‘artery was recanalized or to a maximum of 400,000 IU. Coro- nary arteriograms were performed at regular intervals during STK administration. Recanalization was considered suc- cessful if flow was reestablished in a totally occluded vessel, or improved and the initial stenosis reduced in a subtotally occluded vessel. STK recanalization was successful in 9 pa- tients with total occlusions and in the 2 with subtotal occlu- sions. In 7 patients STK recanalization was unsuccessful.

Angioplasty: Immediately after STK, PTCAs was at- tempted in the 18 patients. Movable guidewire angioplasty systems were not used. The mean time from onset of symp- toms of AM1 to PTCA was 338 & 151 minutes (* standard deviation) (Table I). PTCA was considered successful when it resulted in recanalization and reestablishment of flow in a totally occluded artery, or an increase of more than 30% in the diameter of the lumen in a partially occluded artery. PTCA was attempted only in the infarct-related artery.

Management and follow-up: After PTCA, a No. 9Fr ar- terial sheath was left in the femoral artery for 12 to 16 hours while the patients were monitored in the coronary unit.

Heparin, 1,000 to 1,500 IU/hour, was continuously infused to maintain the partial thromboplastin time 2 to 2l/z times con- trol for 3 to 5 days. All patients received dipyridamole or as- pirin at least until follow-up cardiac catheterization. Oral anticoagulant treatment was not used routinely. Nitrates, calcium and P-blocking agents were used at the discretion of the attending physician. All patients with successful PTCA underwent follow-up cardiac catheterization before hospital discharge. Left ventricular volumes were derived from biplane left ventriculography.7,8

Statistical analysis: Data are reported as percentages and mean f standard error of the mean. The significance of dif- ference was assessed by paired t test (continuous variables) and by analysis of covariance (improvement in ejection frac- tion as dependent variable and collateral vessels time to re- perfusion and late patency of the infarct artery as independent variables).

Results

Success and failure: PTCA was successful in 13 of 18 patients (72%): in 9 of 11 with a residual stenosis after tbrombolytic therapy, and in 4 of 7 with persistent total coronary occlusions.

In the 4 patients with totally occluded arteries in whom PTCA was successful, the dilatation catheter was advanced through the occlusion site and anterograde flow documented by injection of contrast media. The balloon was usually inflated several times at this site until no significant transstenotic pressure gradient (mean less than 15 mm Hg) was present.

In the 13 patients with successful PTCA, the degree of coronary artery obstruction was reduced from 91 f 2% to 27 f 7% (p <O.OOl) and the mean transste- notic pressure gradient from 38 f 5 to 6 f 2 mm Hg (p <O.Ol). Figures 1 and 2 illustrate successful PTCA in 2 patients.

PTCA was unsuccessful in 5 of 18 patients (28%): in 3 patients a total occlusion could not be crossed and in 2 with residual stenoses it was associated with complications.

50 CORONARY ANGIOPLASTY IN MYOCARDIAL INFARCTION

Complications and mortality: Two patients had complications related to PTCA. The first complication developed in a woman with an evolving anterolateral AM1 (patient 5) associated right bundle branch block, recurrent ventricular tachycardia, and shock. After thrombolytic recanalization of the totally occluded left anterior descending artery, and as the dilatation cath- eter was being advanced across a residual 90% stenosis in the midsegment of the artery, ventricular fibrillation developed. Electrical cardioversion restored sinus rhythm and vital signs. Angiograms revealed patency of the artery, with no change in the midsegment stenosis and slow distal flow. The procedure was terminated, and urgent coronary bypass surgery was performed. The patient died in the operating room. She represents the only in-hospital death (1 of 18 patients or [5.5%]). The second complication occurred in a man with an evolving inferior AM1 (patient 6) in whom the right coronary artery was recanalized with STK, leaving a severe 95% proximal stenosis. PTCA resulted in dissection and reocclusion of the right coronary artery. The patient had an otherwise uncomplicated hospital course.

Hospital course and follow-up: Hemorrhagic complications occurred in 5 patients. Two had recurrent bleeding with hematoma formation at the femoral puncture site, 1 had upper gastrointestinal bleeding, 1 had flank pain and hematuria, and 1 had a fall in he- matocrit level during treatment with heparin. In all patients, bleeding resolved without consequences after heparin administration was discontinued.

Patient 3 had anterolateral reinfarction 5 days after successful PTCA of the left anterior descending coro- nary artery. Cardiac catheterization revealed reocclu- sion of the artery, and urgent coronary bypass surgery was performed without complication.

The remaining 12 patients with successful PTCA had a stable and uneventful hospital course and underwent follow-up cardiac catheterization and angiography at a mean of 12 days (range 8 to 17). The infarct-related artery was patent in 9 (75%j. In these 9 patients, the residual stenosis present immediately after PTCA (25 f 8%) was unchanged at follow-up study (31 f 8%, dif- ference not significant [NS]). Left ventricular angiog- raphy revealed no changes in left ventricular end-dia- stolic volume (initial 86 f 6 ml/m2, follow-up 91 f 6 ml/m2, NS), while left ventricular ejection fraction in- creased (>0.04) in 5, decreased (>0.04) in 3 and was unchanged in 1 patient. An increase in ejection fraction was always associated with an improvement in wall motion in the infarct zone. The 4 patients in whom left ventricular ejection fraction did not increase (patients 7,9,12 and 14) were receiving P-blocking agents at the time of follow-up cardiac catheterization. Compared with patients in whom left ventricular ejection fraction did not improve, those in whom it increased more fre- quently had collateral vessels to the distal portion of the occluded infarct-related artery (p = 0.04), a shorter time from onset of symptoms to PTCA (p = 0.15), and a patent infarct-related artery at follow-up angiography (p = 0.04).

In 3 patients (25%) the infarct-related artery had reoccluded. Review of the hospital course in these 3

January 7, 1985 THE AMERICAN JOURNAL i3F CAPSIOLOGY Volume 55 56

patients (nos. 10, 17 and 18) did not reveal a clinical event (chest pain, ST-segment changes during elec- trocardiographic monitoring, frequent or sustained ventricular arrhythmias or paroxysmal dyspnea) that could have been temporally associated to

iscussion In patients with evolving AMI, thrombotic occlusion

of the infarct-related artery is frequently demonstrated if angiographic studies are performed soon after the onset of symptoms9 Intracoronarv STK can recanalize

rethrombosis. the occluded artery in 60 to 90% of patients.24J0J1

FIGURE 1. Right coronary angiograms (caudocranial left anterior oblique projection) in patient 2, in whom an in- ferior acute myocardial infarction was evolving. A, the right coronary artery is totally occluded in the midsegment (arrow). B, after recanalization with streptokinase, a severe residual stenosis (arrow) is present. C, the balloon dilatation catheter has been advanced and is inflated at the site of stenosis. D, after angioplasty, the right coro- nary artery has no residual stenosis.

FIGURE 2. Left coronary angiograms (left lateral pro- jection) in patient 11, in whom an anterior acute myo- cardial infarction was evolving. A, the left anterior descending artery is totally occluded in the proximal segment (arrow), after unsuccessful administration of streptokinase. B, the 2 radiopaque markers (tong arrows) identify the position of the balloon dilatation catheter, which has been advanced through the occlusion site. The distal portion of the left anterior descending artery is faintly visualized (short arrows) with contrast medium injected through the balloon dilatation catheter. C, the balloon dilatation catheter is inflated at the site of oc- clusion. D, after angioplasty, no residual stenosis is present.

52 CORONARY ANGIOPLASTY IN MYOCARDIAL INFARCTION

High-grade stenoses usually remain at the site of the thrombotic occlusion, and may prevent complete re- vascularization, or result in rethrombosis.2,4,5 Reoc- elusion has been reported in 5 to 32% of patients undergoing angiography 7 days to 11 months after thrombolysis.2-4J2 Furthermore, patients frequently have angina and eventually require surgery or PTCA.2-4 Thus, PTCA immediately after thrombolysis may be an attractive option to prevent reocclusion and revas- cularize selected patients with AMI. However, the po- tential benefits of PTCA should outweigh the risks of the procedure in acutely ill patients, who are frequently hemodynamically unstable, and with a lytic state from STK.lr

We attempted PTCA immediately after intracoro- nary STK treatment in a selected group of patients with evolving AMI. PTCA was successful in most patients with residual coronary stenoses, and in some with per- sistent total coronary occlusions. Follow-up cardiac catheterization, performed in all patients with suc- cessful PTCA, revealed persistent patency of the in- farct-related artery in most patients, and this was as- sociated with preservation of the initial left ventricular end-diastolic volume. However, 4 of 13 patients (31%) had early reocclusion of the infarct-related artery, which was silent and not associated with a new clinical event in (23%). Complications occurred infrequently, and were associated with a low mortality rate (1 of 18,5.5%).

In this study, PTCA was successful in 72% of patients, a success rate similar to that of elective PTCA per- formed in patients with more stable coronary disease, not with evolving AMI.r3J4 We dilated 4 totally oc- cluded arteries. The ability of PTCA to recanalize a totally occluded artery has been reported,15 and rep- resents a unique therapeutic option in selected patients with AM1 in whom thrombolysis is contraindicated or has failed to restore blood flow. New movable guidewire PTCA systems may result in higher success and lower complication rates.15

Reocclusion after angioplasty: Four of 13 patients (31%) with successful PTCA of the infarct-related artery had reocclusion of the vessel, demonstrated by angiog- raphy before hospital dicharge. One patient (no. 3) had reinfarction with angiographic confirmation of re- thrombosis. The other 3 (patients 10, 17 and 18) had clinically silent reocclusions. Although our patient population was small, these findings suggest that a successful PTCA may not prevent rethrombosis, and a clinically uneventful hospital course does not exclude reocclusion. The rethrombosis rate probably could have been reduced by more aggressive anticoagulation. However, it was not our purpose to evaluate the benefits of anticoagulation, but rather the ability of PTCA to prevent thrombotic reocclusion of the infarct-related artery. Thus, despite these limitations, the observation that a successful PTCA does not necessarily prevent rethrombosis is important and should have relevant clinical implications when evaluating therapeutic op- tions in patients with AMI. The relatively high rate of reocclusion observed in our patients could be related to compression and molding of thrombi against the arterial

wall, which may propagate and result in reocclusion. Whether additional administration of STK after PTCA, or more aggressive heparin therapy would result in a lower rethrombosis rate is not known.

Left ventricular function after angioplasty: Pa- tients in whom the infarct-related artery remained patent after PTCA had no changes in left ventricular end-diastolic volume. This was associated with a re- duction in end-systolic volume and an increase in ejec- tion fraction in those not receiving ,&blocking drugs at follow-up angiography. After AM1 treated conven- tionally, there is progressive left ventricular dilatation in proportion to the size of the infarction.16rg Thus, the absence of left ventricular dilatation associated with persistent patency of the infarct-related artery probably reflects a reduction of infarct size and preservation of ventricular myocardium.

Hospital mortality: One critically ill patient died during urgent coronary bypass surgery after unsuc- cessful PTCA. Our population was nonrandomized, selected and too small to allow us to draw conclusions concerning hospital mortality from PTCA during AMI. However, several patients had reduced cardiac index, elevated left ventricular filling pressure, and reduced ejection fraction, variables associated with a high mortality rate in AML20s21 Thus, a mortality rate of 5.5% compares favorably with that observed when more conventional modalities of treatment are used.22

Acknowledgment: We gratefully acknowledge the secre- tarial assistance of Kay Stephens.

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