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Early Percutaneous Transluminal Coronary Angioplasty or Coronary Bypass Surgery Following Thrombolytic Treatment of Acute Myocardial Infarction
Early Percutaneous Transluminal Coronary Angioplasty or Coronary Bypass Surgery Following Thrombolytic Treatment of Acute Myocardiallnfarction* Bah I. Salem , M.D. , F.G.G.P. ; Siddhesh Gowda , M .B .; Maged Baikal, M.D . , F.G .G.P.; Ronald Leidenfrost, M .D .; James L. Gox, M .D . , F.G.G.P.t; and Thomas Ferguson , M .D . , F.G.G.P.t
Coronary reocclusion rates following intracoronary streptokinase (IC-SK) infusion remain significantly high despite anticoagulation. Early intervention by coronary angioplasty (PTCA) or coronary bypass surgery (CABG) was advocated to minimize such risk and/or maintain coronary reperfusion, Of 71 consecutive patients (60 men, 11women; mean age, 54.9 years) who underwent IC-SK infusion for acute myocardial infarction (MI) 50 had early CABG, 18 had PTCA, and three had both procedures. Sixty-four of the 71 had successful thrombolysis. Thirty-six patients had either CABG or PTCA within three days, 22 patients within seven days, and 13 patients within two weeks. There was no immediate or in-hospital mortality, and all patients remained alive through the follow-up period of three to 36
N onsurgica J corona ry reperfusion in acute myocar-
dial infarction (MI) has b een achieved b y throm bo lytic age nts suc h as st reptoki nase , urokinase , and tissue pl asminogen activators with variab le degrees of success . 1-8 Recent studies h ave de monstrated the value of suc h reperfusion in certain subsets of patients with re d uction of in-hospital an d on e-year mortality.9,10 Improvement of glob al and regional left ventricul ar fun ction has also b een demon strated with early reperfusion by several studies . 11·16 However, many p atients remain at risk of reoccIusion following recanalizati on , wh ich, according to some series, could be as h igh as 30 p ercent. 17,16 Pati ents with crit ical le sion s are especially at high r isk d esp ite adeq uate anticoagulation. 17 To m inimize this proble m, we b elieve that early ut ilization of percutan eous translu minal coronar y angio plasty (PTCA) or coronary arte r y bypas s grafting (CABG) in suitab le candidate s could play an important role. In this study, we present our exp erien ce in 130 patients who unde rwent intracoronar y streptokinase (IC -SK) administration for acute MI. Seventy-on e patients from this group underwent early CABG and/ or PTCA soon after thrombo lytic treatment. These · From the Departm ent or Cardiology and Cardiovascular Surger y. St. Lukes Hospital, and t Department of'Cardio-Thoracic Surger y, W;lShlngton Universit y School or Medicine. St. Louis. Rcprinl requests: Dr. Salem , 224 SOIlIIl Woods Mill Road. SlIilc 710. St . LOllis 63017
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months. Functional class (FC) 1was achieved in 45 patients, FC 2 in 22 patients, FC 3 in three patients, and FC 4 in one patient. Sixty-seven patients (94 percent) were free of chest pain through the follow-up period. These data suggest that early intervention by CABG and/or PTCA in suitable candidates could be achieved with reduced risk and expected to yield favorable results. This favorable trend could be related to maintenance of myocardial perfusion by these procedures, initially induced by thrombolysis. Long-term, large-scale studies are needed to confirm the role of optimal timing of such procedures, but we believe that such results indicate that early revascularization yields promising results.
patients were followed up over a period of three months to three years. MATERIALS AND METHO DS
Patient Population
From December 1982 through December 1985, a total of 130 consecutive patients underwent emergency coronary ar ter iography and administration ofIC-SK to the infarct-related vessel. Patien ts admitted with prolonged chest pain were considered for entry to this study if they met the following criteria: (1) prolonge d chest pain suggestive of myocardial ischemia and unr elieved by Nitroglycerin (TNG); (2) ECG abnormalities compatible with acute MI (ST-segment elevation greater than 1 mm or the development of new pathologic Q waves); (3) onset of chest pain within six hou rs of arrival at the emergency room. Myocardial infarction was confirmed by serial det ermination of plasma MB creatine kinase (MB CK). Patients were excluded from this study if they were above 75 years of age, survivors of cardiopulmonary arrest, uncontrolled severe hypertension , active bleeding, recent major surgery, or cerebrovascular accident. All patients who entered this study had an informed consent signed prior to any acute intervention. Intravenous medications included 5 mg of diazepam (Valium), 25 to 50 mg of diphenhydramine (Benadryl), as well as 250 mg of hydrocortisone 21-sodium succinate (Solu-Cortef). Prophylactic IV lidocaine at 1- to 3-mglmin drip was used in most patients for 24 to 48 hours . All patie nts underwent left-sided cardiac catheterization with coronary ar teriography by the femoral approach under systemic anticoagulation with 6,000 units of heparin. Number 8 French (U. S.C.I.) sheaths were inserted percutaneously into the right femoral artery and vein at the beginning of the proced ure. The femoral venous line was used for prophylactic pacing Coronary Angioplasty vs Bypass Surgery in Acute Myocardial Infarction (Salem et aI)
or later insertion of a Swan-Ganz catheter, if indicated. Each patient received a mean total dose of 440,000 units of intracoronary streptokinase, with an overall infusion time of 50 minutes. Sixty-five patients had attempted mechanical lysis of the clot by soft guide wire (Bentson .035 inch, 145 em; Cook, Inc). Subsequently, repeated coronary arteriography of the infarct-related vessel was performed. Left ventriculography in the right anterior oblique view was also performed in each case using No 7 F pink pigtail catheter (Cook, Inc). Left ventricular end-diastolic pressure was measured pre- and post-left ventriculography. At the end of the procedure, all patients were transferred to the coronary care unit with femoral sheaths in place for obtaining blood samples. Coagulation studies and MB CK enzyme determinations were obtained every six hours for 48 hours. A serial12-lead ECG was done for at least three consecutive days. Anticoagulation by heparin and/or by coumadin was continued for all patients with successful thrombolysis until further definitive treatment plans were made. Nitrates and/or calcium channel blockers were utilized in the medical treatment of all patients. Angiographic data were reviewed by at least three participants in this study. Coronary angiographic lesions were estimated by visual observation. Coronary bypass surgery was recommended to patients with left main or multivessel disease with 70 percent or more luminal narrowing. Coronary angioplasty was performed in patients with single-vessel disease, ie, for the infarct-related vessel with 70 percent or more residual narrowing. Patients with diffuse coronary artery disease or with an ejection fraction less than 20 percent were treated medically (Fig 1). RESULTS
Clinical Characteristics Among 130 patients who underwent IC-SK, there were 109 men and 21 women, with a mean age of 54. 9 years. Patients were studied within a mean period of 4.1 ± 2. 7 hours from the onset of chest pain (Table 1). Seventy-one of such patients (60 men and 11women) underwent CABG and/or PTCA following IC-SK
Table I-Clinical Profile No. (% Total) Total No. of CABG/PTCA group Mean age, yr Males Females Smoking Hypertension Family history Diabetes mellitus Previous myocardial infarction (MI) Hyperlipidemia Acute anterior or anterolateral MI Acute inferior or inferoposterior MI Strict posterior MI Timing of IC-SK infusion (hr) Mean follow-up period (mo) Range of follow-up period (mo)
71 (100) 54.9 60 (84.5) 11 (75.5) 44 (61.9) 30 (42.2) 24 (33.8) 10 (14.1) 11 (15.4) 9 (12.6) 34 (47.8) 35 (49.3) 2 (2.8) 4.1±2.7 16.4±10.8 3-36
(Scheme). Clinical profile, as well as coronary risk factors and location of MI for this subset of patients were reviewed as shown in Table 1.
Hemodynamic and Angiographic Data Mean left ventricular (LV) end-diastolic pressure was 22±7.1 mm Hg. Their mean LV ejection fraction was 0.52 ± 0.12 as estimated by the regression equation developed by Kennedy et al" using single plain right anterior oblique cineangiogram. Left ventricular wall motion abnormalities were also reviewed from the same view and coincided with the infarct site, except for six patients who had near-normal LVwall motion. Recanalizations of the infarct-related vessel was
ALL IC-St< PATIENTS
MaillS
F8males
(21J
(109)
Not ReC8nlllized Females
Recanalized Males (26)
(If)
FernalllB (17)
"'es 1B3)
ALL CABGIPTCA PATIENTS Males (60)
PTCA
r:b
FIGURE 1. Number of patients in each intervention: intracoronary streptokinase (IC-SK), coronary bypass surgery (CABG), and coronary angioplasty (PTCA). CHEST I 91 I 5 I MAY. 1987
649
Table 2-Timing of Intervention by Coronary Bypass Surgery (CAB G) or Coronary Angiopwsty (PTCA) or Both Timing of Intervention
CABG
PTCA
Both (CABG + PTCA)
Ist 24 hr 2nd-3rd day 4th-7th day 8-14th day Total
6 14 18 12 50
10 3 4 1 18
1 2 0 0 3
Total 17 19 22 13 71
achieved in 77 percent (100/130). In the 71 CABG/ PTCA group of patients, 64 had successful thrombolysis. In this latter subset of patients, 17 percent (12/71) had left main disease, and triple-vessel coronary artery disease was encountered in 51 percent (36/71), two-vessel disease in 32 percent (23/71), and one vessel disease in 20 percent (14/71). All lesions following recanalization showed 70 percent or greater luminal narrowing.
Percutaneous Transluminal Coronary Angioplasty Twenty-one patients who underwent successful thrombolysis underwent PTCA of the infarct-related vessel (Table 2). Ten patients underwent this procedure either at the same setting of IC-SK administration or within 24 hours. Successful results were achieved in 81 perccnt(1'7/21) andwore considered-so ifthc gradient across the stenotic lesion was less than 20 mm Hg with less than 30 percent residual narrowing. In four patients, this procedure was unsuccessful. One patient developed acute reocclusion, one had inadequate dilatation, and another was considered unsuccessful because of inability to cross the lesion. Another patient developed major dissection and reocclusion that required emergency surgery. Three patients underwent CABG following PTCA due to reocclusion and dissection in two and inadequate dilatation in another. All three patients had uneventful postoperative course.
Coronary Artery Bypass Surgery Fifty patients were judged to be candidates for CABG on the basis of early postinfarction angina, or left main and multivessel disease with 70 percent or more luminal narrowing. Forty-three of these patients had successful recanalization, with grade 2 to 3 perfusion as defined by the TIMI trial. 42 Additionally, three other patients had such a procedure after a prior attempt at angioplasty (Scheme). The majority of the patients underwent surgical intervention soon after their acute MI, with an average of 4.1 grafts per patient. There was no immediate or in-hospital mortality in all surgical patients. Excessive postoperative bleeding was encountered in four patients, and two needed reexploration: one for 650
Table 3-Functional Status According to New York Heart Association After Coronary Bypass Surgery or Angiopwsty No. of Patients (% Total)
Functional Class
45 22 3 1 71
1 2 3 4 Thtal
(63.4) (30.9) (4.2) (1.4) (100)
mediastinal bleeding and the other for oozing from the site of a graft. Two of those patients had CABG within the first 24 hours, and the other two patients were operated on after the third and fifth day following ICSK treatment, respectively. One patient required intra-aortic balloon pump for three days and developed nonfatal pulmonary emboli, and one patient had perioperative MI.
Follow-up of Patients with PTCA and/or CABG Data were reviewed on 71 patients who had either PTCA or CABG within two weeks following their MI, and follow-up data were pooled for a period of three to 36 months (16.4 ± 10.8 months). Functional status of these patients was assessed and tabulated according to New York Heart Association (Table 3). The majority of patients (94 percent, 67/71) were free of chest pain and were able to go back to work, and- four patients had excrtional angina thatrequired medical treatment. Patients in FC 1 or 2 composed the majority of these patients (94 percent, 67/71). Three patients were in FC 3, and one patient remained in congestive heart failure (FC 4). Postoperative treadmill exercise data were available on 33 patients. They achieved 81.6 ± 11percent of their predicted maximal heart rate, and none had chest pain during or immediately after exercise. Treadmill test was negative in 61 percent (20/33), equivocal in 4, and positive in nine on the basis of either ST-segment depression or elevation at the site of their prior MI. Of these patients evaluated by exercise testing, 23 had CABG and ten had PTCA. All 71 patients remained alive through the follow-up period. DISCUSSION
This study addresses the results of early intervention by PTCA and/or CABG within two weeks following IC-SK treatment. Furthermore, extended follow-up data over a mean period of 16.4 months (three to 36 months) are presented. Most previously reported series on patients undergoing similar therapeutic interventions were limited in number, and their followup status was not emphasized. 19-40 Several investigators have demonstrated the feasibility of these procedures during or shortly after acute MI with acceptable risks. 19-40 The rationale behind this approach lies in the reportedly high rate of reocclusion Coronary Angioplasty vs Bypass Surgery in Acute Myocardial Infarction (Salem et all
of the reperfused coronary arteries.v"" Reocclusion rates vary but may be as high as 30 percent." In some series the incidence of early and late recurrent ischemic events following IC-SK infusion were noted in II to 29 percent of such patients." Hence, the complementary role of revascularization procedures seems to be crucial, and the overall risk in most series did not seem to have a substantial difference from those done electively. The potential advantage of PTCA along with or shortly after IC-SK treatment has been demonstrated to relieve critical residual lesions. 19-26 In our study, 21 patients underwent PTCA, and ten had this procedure either at the same setting or within 24 hours from ICSK infusion. Successful results were achieved in 81 percent of the patients, which seems to be comparable with results reported from other series.":" There was no difference in the success rate of earlier vs later PTCA procedures in our series. Complications known to occur with PTCA such as coronary dissection, spasm, and subintimal hematoma remain a major concern, particularly when the procedure is performed concomitantly after IC-SK infusion. Combination of IC-SK infusion and PTCA has also been reported with reasonable success rates. 19,21-26 The importance of stand-by cardiovascular surgery backup should be emphasized when this procedure is contemplated. Angioplasty-related mortality in these circumstances has been reported from 0 to 7.7 percent. 19,20.23.25.27 Late restenosis and reocclusion" are among other anticipated problems, and we generally recommend anticoagulation by coumadin for three to six months, followed by long-term use of aspirin and/or dipyridamole. The safe performance ofCABG soon after IC-SK has also been demonstrated.Y" Accepted indications for bypass surgery include: critical left main lesions, postinfarction angina with multivessel disease, or after failed PTCA. Additionally, significant improvement in left ventricular function as a result of thrombolytic therapy has been suggested by others as another indication for early surgery.'?" The inhospital postoperative mortality in some reported series ranged from 0 to 4 percent. 27-37,39,40 However, higher mortality figures may be anticipated in patients with more jeopardized left ventricular function. Walker et aPB reported a 9 percent mortality (4/44 patients) when seven of those patients had cardiogenic shock. Among our series of 53 patients who underwent CABG, there was no in-hospital or late mortality through the followup period. Most of our patients were operated on early during their hospitalization (Table 2). The risk of excessive postoperative bleeding is an important concern when surgery is performed less than 24 hours from IC-SK infusion. 34,36.37 An average of 8.2 units of blood transfusions per patient was needed in a series
reported by Skinner et aP6 when CABG surgery was done immediately following thrombolytic therapy. In our series, two patients required reexploration because of this problem. We try to avoid operating on these patients immediately following thrombolytic therapy to minimize this risk. Previous long-term follow-up data on large numbers of patients remain scanty. Mathey et al' reported earlier on a series of 48 patients who underwent CABG following successful thrombolytic therapy and were followed up over a three- to nine-month period. Fortyone (85 percent) patients were asymptomatic; two patients had postoperative angina, two had reinfarctions, and there were two late deaths. Graft patency was documented in 24 of29 patients studied. Similarly, Sterling et a}2B followed up 41 patients for six to 24 months and reported no reinfarctions and one late cardiac death. Another study by Wilson and associates" followed up 51 patients from six weeks to 18 months, and 45 patients (88 percent) were able to go back to work. Our series included 71 patients who underwent CABG and/or PTCA within two weeks of the onset of their MI and were followed up from three to 36 months. Ninety-four percent of the patients were free of angina and were in either FC 1 or 2 (Table 3). One patient had early nonfatal, nontransmural MI with no early or late postoperative mortality. Additionally, treadmill stress testing in 33 patients from our series showed no evidence of exercise-induced angina, and the majority of these patients had a negative ischemic response. Such encouraging results are comparable to those of earlier series, and our extended follow-up results seem to indicate a favorable outcome for this subset of patients.
Clinical Implications Management of residual coronary lesions following thrombolytic therapy is likely to remain a crucial issue regardless of the type of agent or the method used for such treatment. Our results do indicate that early interventions by CABG and/or PTCA are not merely feasible but seem to be beneficial in the management and outcome of patients with acute MI. It also seems reasonable to attribute those favorable results incurred to the beneficial role of these procedures. While the decision as well as the optimal timing of these interventions may have to be individualized, we believe that early revascularization in suitable candidates with critical coronary lesions should be recommended. However, large-scale studies with extended follow-up will be needed to enable us to confirm such an encouraging trend. ACKNOWLEDGMENT: We wish to thank Yvette Segrass for the preparation of this manuscript and Jim Quirin for his technical assistance. CHEST / 91 / 5 / MAY, 1987
651
REFERENCES 1 Rentrop P, Blanke H, Karsch KR, Kaiser H, Kostering H, Leitz K. Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina. Circulation 1981; 63:307-17 2 Merx W; Dorr R, Rentrop P, Blanke H, Karsch KR, Mathey DG, et al. Evaluation and effectiveness of intracoronary streptokinase infusion in acute myocardial infarction: post-procedure management and hospital course in 204 patients. Am Heart J 1981; 102: 1181-87 3 Ganz W, Buchbinder N, Marcus H, Mondkar A, Maddahi J, Charuzi Y, et al. Intracoronary thrombolysis in evolving myocardial infarction. Am Heart J 1981; 101:4-13 4 Mathey DG, Kuck KH, Tilsner V, Krebber HJ, Bliefield W. Nonsurgical coronary artery recanalization in patients with acute myocardial infarction. Circulation 1981; 63:489-97 5 Van de Wen, Ludbrook PA, Bergmann SR, Tiefenbrunn AJ, Fox KA, DeGeest H, et al. Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction. N Engl J Med 1984; 310:609-13 6 Ganz W, Geft I, Maddahi J, Berman D, Charuzi Y, Shah PK, et al. Non-surgical reperfusion in evolving myocardial infarction. Am Coil Cardiol1983; 1:1247-53 7 Taylor GJ, Mikell FL, Moses HW, Dove JT, Batchhelder JE, Thull A, et al. Intravenous versus intracoronary streptokinase therapy for acute myocardial infarction in community hospitals. Am J Cardiol1984; 54:256-60 8 Van de Werf F, Bergmann SR, Fox KA, DeGeest H, Hoyng CF, Sobel BE, et al. Coronary thrombolysis with intravenously administered human tissue-type plasminogen activator produced by recombinant DNA technology. Circulation 1984; 69:605-10 Y Kennedy jw. Ritchie jL, Davis KH, Fritz jK~Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1983; 309:1477-82 10 Kennedy JW; Ritchie JL, Davis KB, Stadius ML, Maynard C, Fritz JK. The Western Washington Randomized Trial of intracoronary streptokinase in acute myocardial infarction: a 12month follow-up report. N Engl J Med 1985; 312:1073-78 11 Reduto LA, Smalling RW, Freund GC, Gould KL. Intracoronary streptokinase in patients with acute myocardial infarction: effects of reperfusion on left ventricular performance. Am J Cardiol 1981; 48:403-09 12 Sheehan FH, Mathey DG, Schafer J, Krebber HJ, Dodge H. Effect of intervention in salvaging left ventricular function in acute myocardial infarction: a study of intracoronary streptokinase. Am J Cardiol1983; 52:431-38 13 Raizner AE, Tortoledo FA, Verani MS, Van Reet RE, Young JB, Rickman FD, et al. Intracoronary thrombolytic therapy in acute myocardial infarction: a prospective, randomized, controlled trial. Am J Cardiol1985; 55:301-08 14 Smalling RW, Fuentes F, Mathews MW, Freund BS, Hicks CH, Reduto LA, et al. Sustained improvement in left ventricular function and mortality by intracoronary streptokinase administration during evolving myocardial infarction. Circulation 1983; 68:131-38 15 Ferguson DW, White CW, Shiventz JL, Brayden Gp, Kelly KJ, Kioschos M, et al. Influence of baseline ejection fraction and success of thrombolysis on mortality and ventricular function after acute myocardial infarction. Am J Cardiol1984; 54:705-11 16 Sobel BE, Geltman EM, Tiefenbrunn AJ, Jaffe AS, Spadaro JJ, Ter-Pogossian MM, et al. Improvement of regional myocardial metabolism after coronary thrombosis induced by a tissue-type plasminogen activator or streptokinase. Circulation 1984; 69:983-90 17 Harrison DG, Ferguson DW, Collins SM, Skorton DJ, Erickson EE, Kioschos M, et al. Hethrombosis after reperfusion with
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streptokinase: importance of geometry of residual lesions. Circulation 1984; 69:991-99 Gold HK, Leinbach RC, Palacios IF, Yasuda T, Block PC, Buckley MJ, et al. Coronary reocclusion after selective administration of streptokinase. Circulation 1983; 68(suppl):150-54 Meyer J, Merx W, Schmitz H, Erbel R, Kresslich T, Dorr R, et al. Percutaneous transluminal coronary angioplasty immediately after intracoronary streptolysis of transmural myocardial infarction. Circulation 1982; 66:905-13 Papapietro SE, Maclean WAH, Stanley AWH, Hess RG, Corley N, Arciniegas JG, et al. Percutaneous transluminal coronary angioplasty after intracoronary streptokinase in evolving myocardial infarctions. Am J Cardiol1985; 55:48-53 Holmes DR, Smith HC, Vlietstra RE, Nashimura RA, Reeder GS, Bove AA, et al. Percutaneous transluminal coronary angioplasty, alone or in combination with streptokinase therapy, during acute myocardial infarction. Mayo Clin Proc 1985; 60:449-56 Hartzler GO, Rutherford BD, McConahay DR. Percutaneous transluminal coronary angioplasty: application for acute myocardial infarction. Am J Cardiol1984; 53:117C-121C Hartzler GO, Rutherford BD, McConahay DR, Johnson WL. McCallister BD, Gura GM, et al. Percutaneous transluminal coronary angioplasty with and without thrombolytic therapy for treatment of acute myocardial infarction. Am Heart J 1983; 106:965-73 Yasuno M, Saito Y, Ishida M, Suzuki K, Endo S, Takahashi M. Effects of percutaneous transluminal coronary angioplasty: intracoronary thrombolysis with urokinase in acute myocardial infarction. Am J Cardiol1984; 93:1217-20 Gold HK, Cowley MJ, Palacios IF, Vetrovec GW; Akins CW; Block PC, et al. Combined intracoronary streptokinase infusion and coronary angioplasty during acute myocardial inlarction. Am J Cardiol1984; 53:122C-25C Serruys PW, Wijns W, Van Den Banel M, Fioretti P, Simoons ML, Kooijman CJ, et al. Is transluminal coronary angioplasty mandatory after successful thrombolysis? Quantitative coronary angiographic study. Br Heart J 1984; 50:257-65 Lee G, LowRI, Takedap, Joep, DeMariaAN, AmsterdamEA, et al. Importance of follow-up medical and surgical approaches to prevent reinfarction, reocclusion and recurrent angina following intracoronary thrombolysis with streptokinase in acute myocardial infarction. Am Heart J 1982; 104:921-24 Sterling Rp, Walker WE, Weiland Ap, Freund GC, Guentes F, Smalling RW, et al. Early bypass grafting following intracoronary thrombolysis with streptokinase. J Thorac Cardiovasc Surg 1984; 87:487-92 Mathey DG, Rodewald G, Rentrop P, Leitz K, Merx W; Messmer BJ, et al. Intracoronary streptokinase thrombolytic recanalization and subsequent surgical bypass of remaining atherosclerotic effecting reduced infarct size, preventing reinfarction and improving left ventricular function. Am Heart J 1981; 102:1194-1201 Dodge HT, Sheehan FH, Mathey DG, Brown BG, Kennedy JW Usefulness of coronary artery bypass graft surgery of percutaneous transluminal angioplasty after thrombolytic therapy. Circulation 1985; 72(suppl):V39-V45 Urban PL, Cowley M, Goldberg S, Vetrovec G, Hasfillo A, Greenspon AJ, et al. Intracoronary thrombolysis in acute myocardial infarction: clinical course following successful myocardial reperfusion. Am Heart J 1984; 108:873-78 Kay P, Ahmad A, Floten S, Starr A. Emergency coronary artery bypass surgery after intracoronary thrombolysis for evolving myocardial infarction. Br Heart J 1985; 53:260-64 Salem BI, Gowda S, Haikal M, Cox JL. Coronary artery bypass and coronary angioplasty soon after successful intracoronary thrombolysis. Chest 1985; 88:715
CoronaryAngioplasty vs Bypass Surgery in Acute Myocardial Infarction (Salem et al)
34 Richardson RL, Gooch JB, Robbins SG, Garrett HE, Davis JT. Coronary artery bypass grafts: success after selective intracoronary thrombolysis in acute myocardial infarction. Arch Surg 1983; 118:970-72 35 Messmer BJ, Merx W, Meyer J, Bardos P, Minale C, Effert S. New developments in medical-surgical treatment of acute myocardial infarction. Ann Thorac Surg 1983; 35:70-78 36 Skinner JR, Phillips SJ, Zeff RH, Kongtahworn C. Immediate coronary bypass following failed streptokinase infusion in evolving myocardial infarction . J Thorac Cardiovasc Surg 1984; 87:567-70 37 Becher H , Schroder C, Mathey D, Krebber HJ, Tisner V, Bleifeld W. Coronary artery bypass grafting within 24 hours after intracoronary thrombolysis-risk of bleeding. Circulation 1983; 68:suppl III:115 38 Walker WE, Smalling RW, Fuentes F, Gould L, Johnson WF, Reduto LA, et al. Role of coronary artery bypass surgery after
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intracoronary streptokinase infusion for myocardial infarction . Am Heart J 1984; 107:826-29 Wilson JM, Held JS, Wright CB, Abottsmith CW, Callard GM, Mitts DL, et al. Coronary artery bypass surgery following thrombolytic therapy for acute coronary thrombosis . Ann Thorac Surg 1984: 37:212-16 Krebber HJ, Mathey D, Kuck KJ, Kalmar P, Rodewald G, Hill JD. Management of evolving myocardial infarction by intracoronary thrombolysis and subsequent aorto-coronary bypass. Thorac Cardiovasc Surg 1982; 83:186-93 Kennedy JW, 'Irenholrne SE , Kasser IS. Left ventricular volume and mass from single plain cineangiocardiograms: a comparison of anteroposterior and right anterior oblique methods . Am Heart J 1970; 80:343-52 The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med 1985; 312:932-36
ADVANCES IN PULMONARY MEDICINE Dates: June 17-19, 1987 Location: Four Seasons Hotel Vancouver, British Columbia, Canada Co-Sponsors: American College of Chest Physicians University of British Columbia Course Objectives: At the conclusion of the course, the participants will be able to provide answers to some of the key problems facing modern pulmonary medicine. They will be able to solve a number of imaging and pathology interpretation problems. Course Description: This program is designed for those physicians who share an interest in pulmonary disease including intensive care physicians, internists and pulmonary physicians. A nationally recognized faculty comprised of pulmonary and intensive care physicians will lead the conference. This will be a problem-oriented conference and lectures will be directed toward answering specific problems within the fields. Small group sessions will be oriented towards imaging, pulmonary pathology and physiology. Instructional lectures will include lectures and workshops. There will be an evening dinner at the world acclaimed Vancouver Aquarium which will include a Killer Whale show. The timing of this course will allow post -course tours to Alaska, trips throughout the Canadian Rockies and visits to Victoria and Vancouver Island . Tuition: (U.S . Funds ) ACCP members $300.00 ACCP Affiliate members $150.00 Non-members $335.00 Physicians-in-training $170.00 This fee includes all course materials, refreshment breaks and one luncheon. Evening tour and dinner at the Vancouver Aquarium will be available for an additional fee of $35.00 (U.S. Funds) per person. Refunds for cancellations prior to June 1, 1987 will be made, less a $30.00 administrative fee. No refunds will be issued after June 1, 1987. Credit: (Course #ME7209) The Division of Continuing Medical Education, University of British Columbia (UBC) is fully accredited by the Committee on Accreditation of Canadian Medical Schools (CACMS) and the Accreditation Council for Continuing Medical Education (ACC ME) of the United States to sponsor continuing medical education for physicians . As an organization accredited for continuing medical education, the Division of Continuing Medical Education, UBC, designates this continuing medical education activity as meeting the criteria for 25 credit hours in Category 1 of the "Physician Recognition Award of the American Medical Association." For information, contact the Division of Education, American College of Chest Physicians, 911 Busse Highway, Park Ridge, IL 60068 (312:698-2200).
CHEST / 91 / 5 / MAY, 19B7
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Coronary reocclusion rates following intracoronary streptokinase (IC-SK) infusion remain significantly high despite anticoagulation. Early intervention by coronary angioplasty (PTCA) or coronary bypass surgery (CABG) was advocated to minimize such risk and/or maintain coronary reperfusion, Of 71 consecutive patients (60 men, 11women; mean age, 54.9 years) who underwent IC-SK infusion for acute myocardial infarction (MI) 50 had early CABG, 18 had PTCA, and three had both procedures. Sixty-four of the 71 had successful thrombolysis. Thirty-six patients had either CABG or PTCA within three days, 22 patients within seven days, and 13 patients within two weeks. There was no immediate or in-hospital mortality, and all patients remained alive through the follow-up period of three to 36
N onsurgica J corona ry reperfusion in acute myocar-
dial infarction (MI) has b een achieved b y throm bo lytic age nts suc h as st reptoki nase , urokinase , and tissue pl asminogen activators with variab le degrees of success . 1-8 Recent studies h ave de monstrated the value of suc h reperfusion in certain subsets of patients with re d uction of in-hospital an d on e-year mortality.9,10 Improvement of glob al and regional left ventricul ar fun ction has also b een demon strated with early reperfusion by several studies . 11·16 However, many p atients remain at risk of reoccIusion following recanalizati on , wh ich, according to some series, could be as h igh as 30 p ercent. 17,16 Pati ents with crit ical le sion s are especially at high r isk d esp ite adeq uate anticoagulation. 17 To m inimize this proble m, we b elieve that early ut ilization of percutan eous translu minal coronar y angio plasty (PTCA) or coronary arte r y bypas s grafting (CABG) in suitab le candidate s could play an important role. In this study, we present our exp erien ce in 130 patients who unde rwent intracoronar y streptokinase (IC -SK) administration for acute MI. Seventy-on e patients from this group underwent early CABG and/ or PTCA soon after thrombo lytic treatment. These · From the Departm ent or Cardiology and Cardiovascular Surger y. St. Lukes Hospital, and t Department of'Cardio-Thoracic Surger y, W;lShlngton Universit y School or Medicine. St. Louis. Rcprinl requests: Dr. Salem , 224 SOIlIIl Woods Mill Road. SlIilc 710. St . LOllis 63017
648
months. Functional class (FC) 1was achieved in 45 patients, FC 2 in 22 patients, FC 3 in three patients, and FC 4 in one patient. Sixty-seven patients (94 percent) were free of chest pain through the follow-up period. These data suggest that early intervention by CABG and/or PTCA in suitable candidates could be achieved with reduced risk and expected to yield favorable results. This favorable trend could be related to maintenance of myocardial perfusion by these procedures, initially induced by thrombolysis. Long-term, large-scale studies are needed to confirm the role of optimal timing of such procedures, but we believe that such results indicate that early revascularization yields promising results.
patients were followed up over a period of three months to three years. MATERIALS AND METHO DS
Patient Population
From December 1982 through December 1985, a total of 130 consecutive patients underwent emergency coronary ar ter iography and administration ofIC-SK to the infarct-related vessel. Patien ts admitted with prolonged chest pain were considered for entry to this study if they met the following criteria: (1) prolonge d chest pain suggestive of myocardial ischemia and unr elieved by Nitroglycerin (TNG); (2) ECG abnormalities compatible with acute MI (ST-segment elevation greater than 1 mm or the development of new pathologic Q waves); (3) onset of chest pain within six hou rs of arrival at the emergency room. Myocardial infarction was confirmed by serial det ermination of plasma MB creatine kinase (MB CK). Patients were excluded from this study if they were above 75 years of age, survivors of cardiopulmonary arrest, uncontrolled severe hypertension , active bleeding, recent major surgery, or cerebrovascular accident. All patients who entered this study had an informed consent signed prior to any acute intervention. Intravenous medications included 5 mg of diazepam (Valium), 25 to 50 mg of diphenhydramine (Benadryl), as well as 250 mg of hydrocortisone 21-sodium succinate (Solu-Cortef). Prophylactic IV lidocaine at 1- to 3-mglmin drip was used in most patients for 24 to 48 hours . All patie nts underwent left-sided cardiac catheterization with coronary ar teriography by the femoral approach under systemic anticoagulation with 6,000 units of heparin. Number 8 French (U. S.C.I.) sheaths were inserted percutaneously into the right femoral artery and vein at the beginning of the proced ure. The femoral venous line was used for prophylactic pacing Coronary Angioplasty vs Bypass Surgery in Acute Myocardial Infarction (Salem et aI)
or later insertion of a Swan-Ganz catheter, if indicated. Each patient received a mean total dose of 440,000 units of intracoronary streptokinase, with an overall infusion time of 50 minutes. Sixty-five patients had attempted mechanical lysis of the clot by soft guide wire (Bentson .035 inch, 145 em; Cook, Inc). Subsequently, repeated coronary arteriography of the infarct-related vessel was performed. Left ventriculography in the right anterior oblique view was also performed in each case using No 7 F pink pigtail catheter (Cook, Inc). Left ventricular end-diastolic pressure was measured pre- and post-left ventriculography. At the end of the procedure, all patients were transferred to the coronary care unit with femoral sheaths in place for obtaining blood samples. Coagulation studies and MB CK enzyme determinations were obtained every six hours for 48 hours. A serial12-lead ECG was done for at least three consecutive days. Anticoagulation by heparin and/or by coumadin was continued for all patients with successful thrombolysis until further definitive treatment plans were made. Nitrates and/or calcium channel blockers were utilized in the medical treatment of all patients. Angiographic data were reviewed by at least three participants in this study. Coronary angiographic lesions were estimated by visual observation. Coronary bypass surgery was recommended to patients with left main or multivessel disease with 70 percent or more luminal narrowing. Coronary angioplasty was performed in patients with single-vessel disease, ie, for the infarct-related vessel with 70 percent or more residual narrowing. Patients with diffuse coronary artery disease or with an ejection fraction less than 20 percent were treated medically (Fig 1). RESULTS
Clinical Characteristics Among 130 patients who underwent IC-SK, there were 109 men and 21 women, with a mean age of 54. 9 years. Patients were studied within a mean period of 4.1 ± 2. 7 hours from the onset of chest pain (Table 1). Seventy-one of such patients (60 men and 11women) underwent CABG and/or PTCA following IC-SK
Table I-Clinical Profile No. (% Total) Total No. of CABG/PTCA group Mean age, yr Males Females Smoking Hypertension Family history Diabetes mellitus Previous myocardial infarction (MI) Hyperlipidemia Acute anterior or anterolateral MI Acute inferior or inferoposterior MI Strict posterior MI Timing of IC-SK infusion (hr) Mean follow-up period (mo) Range of follow-up period (mo)
71 (100) 54.9 60 (84.5) 11 (75.5) 44 (61.9) 30 (42.2) 24 (33.8) 10 (14.1) 11 (15.4) 9 (12.6) 34 (47.8) 35 (49.3) 2 (2.8) 4.1±2.7 16.4±10.8 3-36
(Scheme). Clinical profile, as well as coronary risk factors and location of MI for this subset of patients were reviewed as shown in Table 1.
Hemodynamic and Angiographic Data Mean left ventricular (LV) end-diastolic pressure was 22±7.1 mm Hg. Their mean LV ejection fraction was 0.52 ± 0.12 as estimated by the regression equation developed by Kennedy et al" using single plain right anterior oblique cineangiogram. Left ventricular wall motion abnormalities were also reviewed from the same view and coincided with the infarct site, except for six patients who had near-normal LVwall motion. Recanalizations of the infarct-related vessel was
ALL IC-St< PATIENTS
MaillS
F8males
(21J
(109)
Not ReC8nlllized Females
Recanalized Males (26)
(If)
FernalllB (17)
"'es 1B3)
ALL CABGIPTCA PATIENTS Males (60)
PTCA
r:b
FIGURE 1. Number of patients in each intervention: intracoronary streptokinase (IC-SK), coronary bypass surgery (CABG), and coronary angioplasty (PTCA). CHEST I 91 I 5 I MAY. 1987
649
Table 2-Timing of Intervention by Coronary Bypass Surgery (CAB G) or Coronary Angiopwsty (PTCA) or Both Timing of Intervention
CABG
PTCA
Both (CABG + PTCA)
Ist 24 hr 2nd-3rd day 4th-7th day 8-14th day Total
6 14 18 12 50
10 3 4 1 18
1 2 0 0 3
Total 17 19 22 13 71
achieved in 77 percent (100/130). In the 71 CABG/ PTCA group of patients, 64 had successful thrombolysis. In this latter subset of patients, 17 percent (12/71) had left main disease, and triple-vessel coronary artery disease was encountered in 51 percent (36/71), two-vessel disease in 32 percent (23/71), and one vessel disease in 20 percent (14/71). All lesions following recanalization showed 70 percent or greater luminal narrowing.
Percutaneous Transluminal Coronary Angioplasty Twenty-one patients who underwent successful thrombolysis underwent PTCA of the infarct-related vessel (Table 2). Ten patients underwent this procedure either at the same setting of IC-SK administration or within 24 hours. Successful results were achieved in 81 perccnt(1'7/21) andwore considered-so ifthc gradient across the stenotic lesion was less than 20 mm Hg with less than 30 percent residual narrowing. In four patients, this procedure was unsuccessful. One patient developed acute reocclusion, one had inadequate dilatation, and another was considered unsuccessful because of inability to cross the lesion. Another patient developed major dissection and reocclusion that required emergency surgery. Three patients underwent CABG following PTCA due to reocclusion and dissection in two and inadequate dilatation in another. All three patients had uneventful postoperative course.
Coronary Artery Bypass Surgery Fifty patients were judged to be candidates for CABG on the basis of early postinfarction angina, or left main and multivessel disease with 70 percent or more luminal narrowing. Forty-three of these patients had successful recanalization, with grade 2 to 3 perfusion as defined by the TIMI trial. 42 Additionally, three other patients had such a procedure after a prior attempt at angioplasty (Scheme). The majority of the patients underwent surgical intervention soon after their acute MI, with an average of 4.1 grafts per patient. There was no immediate or in-hospital mortality in all surgical patients. Excessive postoperative bleeding was encountered in four patients, and two needed reexploration: one for 650
Table 3-Functional Status According to New York Heart Association After Coronary Bypass Surgery or Angiopwsty No. of Patients (% Total)
Functional Class
45 22 3 1 71
1 2 3 4 Thtal
(63.4) (30.9) (4.2) (1.4) (100)
mediastinal bleeding and the other for oozing from the site of a graft. Two of those patients had CABG within the first 24 hours, and the other two patients were operated on after the third and fifth day following ICSK treatment, respectively. One patient required intra-aortic balloon pump for three days and developed nonfatal pulmonary emboli, and one patient had perioperative MI.
Follow-up of Patients with PTCA and/or CABG Data were reviewed on 71 patients who had either PTCA or CABG within two weeks following their MI, and follow-up data were pooled for a period of three to 36 months (16.4 ± 10.8 months). Functional status of these patients was assessed and tabulated according to New York Heart Association (Table 3). The majority of patients (94 percent, 67/71) were free of chest pain and were able to go back to work, and- four patients had excrtional angina thatrequired medical treatment. Patients in FC 1 or 2 composed the majority of these patients (94 percent, 67/71). Three patients were in FC 3, and one patient remained in congestive heart failure (FC 4). Postoperative treadmill exercise data were available on 33 patients. They achieved 81.6 ± 11percent of their predicted maximal heart rate, and none had chest pain during or immediately after exercise. Treadmill test was negative in 61 percent (20/33), equivocal in 4, and positive in nine on the basis of either ST-segment depression or elevation at the site of their prior MI. Of these patients evaluated by exercise testing, 23 had CABG and ten had PTCA. All 71 patients remained alive through the follow-up period. DISCUSSION
This study addresses the results of early intervention by PTCA and/or CABG within two weeks following IC-SK treatment. Furthermore, extended follow-up data over a mean period of 16.4 months (three to 36 months) are presented. Most previously reported series on patients undergoing similar therapeutic interventions were limited in number, and their followup status was not emphasized. 19-40 Several investigators have demonstrated the feasibility of these procedures during or shortly after acute MI with acceptable risks. 19-40 The rationale behind this approach lies in the reportedly high rate of reocclusion Coronary Angioplasty vs Bypass Surgery in Acute Myocardial Infarction (Salem et all
of the reperfused coronary arteries.v"" Reocclusion rates vary but may be as high as 30 percent." In some series the incidence of early and late recurrent ischemic events following IC-SK infusion were noted in II to 29 percent of such patients." Hence, the complementary role of revascularization procedures seems to be crucial, and the overall risk in most series did not seem to have a substantial difference from those done electively. The potential advantage of PTCA along with or shortly after IC-SK treatment has been demonstrated to relieve critical residual lesions. 19-26 In our study, 21 patients underwent PTCA, and ten had this procedure either at the same setting or within 24 hours from ICSK infusion. Successful results were achieved in 81 percent of the patients, which seems to be comparable with results reported from other series.":" There was no difference in the success rate of earlier vs later PTCA procedures in our series. Complications known to occur with PTCA such as coronary dissection, spasm, and subintimal hematoma remain a major concern, particularly when the procedure is performed concomitantly after IC-SK infusion. Combination of IC-SK infusion and PTCA has also been reported with reasonable success rates. 19,21-26 The importance of stand-by cardiovascular surgery backup should be emphasized when this procedure is contemplated. Angioplasty-related mortality in these circumstances has been reported from 0 to 7.7 percent. 19,20.23.25.27 Late restenosis and reocclusion" are among other anticipated problems, and we generally recommend anticoagulation by coumadin for three to six months, followed by long-term use of aspirin and/or dipyridamole. The safe performance ofCABG soon after IC-SK has also been demonstrated.Y" Accepted indications for bypass surgery include: critical left main lesions, postinfarction angina with multivessel disease, or after failed PTCA. Additionally, significant improvement in left ventricular function as a result of thrombolytic therapy has been suggested by others as another indication for early surgery.'?" The inhospital postoperative mortality in some reported series ranged from 0 to 4 percent. 27-37,39,40 However, higher mortality figures may be anticipated in patients with more jeopardized left ventricular function. Walker et aPB reported a 9 percent mortality (4/44 patients) when seven of those patients had cardiogenic shock. Among our series of 53 patients who underwent CABG, there was no in-hospital or late mortality through the followup period. Most of our patients were operated on early during their hospitalization (Table 2). The risk of excessive postoperative bleeding is an important concern when surgery is performed less than 24 hours from IC-SK infusion. 34,36.37 An average of 8.2 units of blood transfusions per patient was needed in a series
reported by Skinner et aP6 when CABG surgery was done immediately following thrombolytic therapy. In our series, two patients required reexploration because of this problem. We try to avoid operating on these patients immediately following thrombolytic therapy to minimize this risk. Previous long-term follow-up data on large numbers of patients remain scanty. Mathey et al' reported earlier on a series of 48 patients who underwent CABG following successful thrombolytic therapy and were followed up over a three- to nine-month period. Fortyone (85 percent) patients were asymptomatic; two patients had postoperative angina, two had reinfarctions, and there were two late deaths. Graft patency was documented in 24 of29 patients studied. Similarly, Sterling et a}2B followed up 41 patients for six to 24 months and reported no reinfarctions and one late cardiac death. Another study by Wilson and associates" followed up 51 patients from six weeks to 18 months, and 45 patients (88 percent) were able to go back to work. Our series included 71 patients who underwent CABG and/or PTCA within two weeks of the onset of their MI and were followed up from three to 36 months. Ninety-four percent of the patients were free of angina and were in either FC 1 or 2 (Table 3). One patient had early nonfatal, nontransmural MI with no early or late postoperative mortality. Additionally, treadmill stress testing in 33 patients from our series showed no evidence of exercise-induced angina, and the majority of these patients had a negative ischemic response. Such encouraging results are comparable to those of earlier series, and our extended follow-up results seem to indicate a favorable outcome for this subset of patients.
Clinical Implications Management of residual coronary lesions following thrombolytic therapy is likely to remain a crucial issue regardless of the type of agent or the method used for such treatment. Our results do indicate that early interventions by CABG and/or PTCA are not merely feasible but seem to be beneficial in the management and outcome of patients with acute MI. It also seems reasonable to attribute those favorable results incurred to the beneficial role of these procedures. While the decision as well as the optimal timing of these interventions may have to be individualized, we believe that early revascularization in suitable candidates with critical coronary lesions should be recommended. However, large-scale studies with extended follow-up will be needed to enable us to confirm such an encouraging trend. ACKNOWLEDGMENT: We wish to thank Yvette Segrass for the preparation of this manuscript and Jim Quirin for his technical assistance. CHEST / 91 / 5 / MAY, 1987
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ADVANCES IN PULMONARY MEDICINE Dates: June 17-19, 1987 Location: Four Seasons Hotel Vancouver, British Columbia, Canada Co-Sponsors: American College of Chest Physicians University of British Columbia Course Objectives: At the conclusion of the course, the participants will be able to provide answers to some of the key problems facing modern pulmonary medicine. They will be able to solve a number of imaging and pathology interpretation problems. Course Description: This program is designed for those physicians who share an interest in pulmonary disease including intensive care physicians, internists and pulmonary physicians. A nationally recognized faculty comprised of pulmonary and intensive care physicians will lead the conference. This will be a problem-oriented conference and lectures will be directed toward answering specific problems within the fields. Small group sessions will be oriented towards imaging, pulmonary pathology and physiology. Instructional lectures will include lectures and workshops. There will be an evening dinner at the world acclaimed Vancouver Aquarium which will include a Killer Whale show. The timing of this course will allow post -course tours to Alaska, trips throughout the Canadian Rockies and visits to Victoria and Vancouver Island . Tuition: (U.S . Funds ) ACCP members $300.00 ACCP Affiliate members $150.00 Non-members $335.00 Physicians-in-training $170.00 This fee includes all course materials, refreshment breaks and one luncheon. Evening tour and dinner at the Vancouver Aquarium will be available for an additional fee of $35.00 (U.S. Funds) per person. Refunds for cancellations prior to June 1, 1987 will be made, less a $30.00 administrative fee. No refunds will be issued after June 1, 1987. Credit: (Course #ME7209) The Division of Continuing Medical Education, University of British Columbia (UBC) is fully accredited by the Committee on Accreditation of Canadian Medical Schools (CACMS) and the Accreditation Council for Continuing Medical Education (ACC ME) of the United States to sponsor continuing medical education for physicians . As an organization accredited for continuing medical education, the Division of Continuing Medical Education, UBC, designates this continuing medical education activity as meeting the criteria for 25 credit hours in Category 1 of the "Physician Recognition Award of the American Medical Association." For information, contact the Division of Education, American College of Chest Physicians, 911 Busse Highway, Park Ridge, IL 60068 (312:698-2200).
CHEST / 91 / 5 / MAY, 19B7
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