American Founded

Journal

in 1925

January

CLINICAL

Heart

1992

Volume

123,

Number

1

INVESTIGATIONS

Myocardial angioplasty

salvage with direct coronary for acute infarction

To assess the changes in myocardial function following direct coronary angioplasty, we evaluated 323 consecutive patients undergoing coronary angioplasty without antecedent thrombolytic therapy for acute myocardial infarction. Left ventricular function was evaluated using contrast ventriculography immediately preangioplasty and at the time of predismissal follow-up angiography (a mean of 7 days after infarction). The global ejection fraction increased from 52.6% to 56.9% (p < 0.0005). Multivariate correlates of improved global left ventricular function included baseline ejection fraction 545%, and a patent infarct vessel at the time of predischarge follow-up anglography. Systolic function in the infarct zone improved by a mean of 30%. Logistic regression analysis identified sustained infarct vessel patency and anterior myocardial infarction as multivariate correlates of improved regional function In the Infarct zone. In patients presenting with baseline ejection fractions 140%, the mean ejection fraction increased from 26% to 42%. Long-term survival was compromised in patients with global ejection fractions of 140% at the time of dismissal. Thus significant improvement in left ventricular function can be expected in the majority of patfents undergoing direct infarct angioplasty. The myocardial salvage appears to be most significant in patients suffering large infarctions, and in those with sustained infarct vessel patency. (AM HEART J lgg2;123:1.)

James H. O’Keefe, Jr., MD, Barry D. Rutherford, MD, David R. McConahay, MD, Warren L. Johnson, Jr., MD, Lee V. Giorgi, MD, Thomas M. Shimshak, MD, Robert W. Ligon, MA, Ben D. McCallister, MD, and Geoffrey 0. Hartzler, MD. Kansas City, MO.

Sudden thrombotic coronary occlusion, the initiating event in acute myocardial infarction, results in myocardial necrosis if timely recanalization does not occur. The amount of myocardial necrosis-i.e., the infarct size-has been firmly documented as the most important determinant of both short- and long-term prognosis after myocardial infarction.lM3 Thrombolytic therapy4-6 and direct infarct angioplasty (without antecedent thrombolysis)7-13 have both been effective in reducing morbidity and mortality with myocardial infarction. Because thrombolytic therapy is logistically simpler and more widely available than direct infarct angioplasty, it has been embraced by From Luke’s Received

Cardiovascular Hospital. for publication

Consultants, May

Inc., 28, 1991;

Mid

America

accepted

July

Heart

10, 1991.

Reprint requests: James H. O’Keefe, Jr., MD, Cardiovascular Inc., Medical Plaza 11-20, 4320 Worm111 Rd., Kansas City, 4/l/33661

Institute,

Consultants, MO 64111.

St.

much of the medical community as the therapy of choice for acute myocardial infarction. However, many centers continue to use direct infarct angioplasty without thrombolytic therapy, and previous studies have reported significant myocardial salvage with this technique. 7l 8pr3 Clinical identification of patients most likely to show recovery of left ventricular function with direct angioplasty might allow for a more judicious application of the technique in those centers where this remains a therapeutic option. Thus the purpose of the current study was to characterize the impact of direct angioplasty on myocardial function and to identify the clinical determinants that were correlated with significant improvement in regional and global left ventricular function. METHODS Study patients. Since November 1980, all patients treated with direct infarct angioplasty have been prospectively entered into a computer data base. For the current

1

January

2

O’Keefe et al.

American

Table

1. Patient Sex

Prior CABG Poor

Systole

LV function

Cardiogenic shock Baseline EF

SEGMENTAL EJECTION FRACTION 50 NORMAL PATIENTS

Ischemic time No. of diseased 1

MI MI

CABG, Coronary artery bypass graft surgery; tion fraction; A41, myocardial infarction.

,

2

3 4 pmlati bunI

5

6

7

diaphragmalii

3

Q 10

11

12

13

14

15 15

17

18

IQ

wea

Fig. 1. Regional wall motion analysis was performed by calculating regional ejection fractions in each of 19 segments in systole and diastole. These calculations were performed in 50 patients with normal left ventricular function and normal coronary arteries. The mean values f 1 standard deviation were calculated by analyzing 50 patients with normal left ventricular function and normal coronary

analysis, all patients with paired preangioplasty and predischarge left ventriculograms were evaluated, This included 323 patients (52%) of the total number of 614 patients who underwent infarct angioplasty between November 1980 and March 1989. Patients were considered for direct infarct angioplasty if the following criteria were met: (1) chest pain consistent with ongoing myocardial ischemia persisting longer than or up to 30 minutes and (2) greater than or equivalent to 1 mm ST segment elevation in two or more contiguous electrocardiographic leads. Patients were excluded from this study for the following reason(s): (1) treatment with a thrombolytic agent for the infarction in progress; (2) acute coronary occlusion after elective angioplasty; and (3) presentation to the emergency room >6 hours after the onset of chest pain without clinical or electrocardiographic evidence of ongoing ischemia. Patients with stuttering ischemia presenting >6 but 40 % . A significant difference in the long-term survival of these two populations was noted (Fig. 7). DISCUSSION

The primary target of interventional (pharmacologic or catheter-based) therapy for acute myocardial infarction is the reestablishment of infarct vessel patency. The most important immediate consequence of prompt restoration of blood flow is the salvage of ischemic, jeopardized myocardium. If the extent of infarction is reduced by reperfusion, this should result in improved short- and long-term morbidity and

Volume Number

123 1

Myocardial

salvage after infarct angioplasty

5

92%

p = ,002

c

30 20

LVEF

>40%

n =

LVEF

~40%

n =

-

+

15

21

29

LVEF

119

175

249

>40%

10 I

0 0

6

I 12

t

I

I

1

18

24

30

38

Months

Fig. 7. Long-term survival as a function of predischargeglobal left ventricular function. Patients with a left ventricular ejection fraction of >40% at the time of dischargehad significantly better long-term survival when compared with those patients with ejection fractions of 140%.

mortality rates. In the current trial of 323 consecutive patients with paired left ventriculograms obtained immediately before infarct angioplasty and prior to hospital dismissal, we have documented a mean increase in global ejection fraction of 6.3 points (from 52.6% to 58.9% 1. Additionally, a 30% improvement in the systolic function in the infarct zone was noted. The patients most likely to demonstrate preservation of left ventricular function with direct infarct angioplasty were those with an extensive amount of jeopardized myocardium and those with sustained infarct vessel patency. The dependency of myocardial salvage on sustained infarct vessel patency was predictable and is consistent with the findings of previous reports.8 The global and regional ejection fractions remained virtually unchanged from preangioplasty to predischarge in those patients with an occluded infarct artery at the time of follow-up. Patients suffering the largest infarcts appeared to benefit most from infarct angioplasty. Thus the very patients most in need of myocardial salvage experienced the most dramatic improvement in left ventricular function. This is perhaps the most important finding of the current study. Ejection fractions in patients with baseline values ~40% improved from 28% to 42 % . Left ventricular function asdetermined by ejection fraction has been consistently found to be the most important determinant in short- or longterm survival after acute infarction.lm3 Improvements of this parameter are almost certainly translated into long-term survival benefits for these patients. The left ventricular function in patients who presented in cardiogenic shock also improved dramati-

tally in this series. Unlike patients presenting without evidence of shock, cardiogenic shock patients demonstrated diffuse recovery of left ventricular function, even in regions not subtended by the infarct artery. This recovery in myocardial function remote from the infarct zone likely occurs as a result of increased coronary perfusion pressure associated with improved hemodynamic parameters. This improvement in myocardial function is probably responsible for the encouraging mortality figures reported with direct angioplasty for cardiogenic shock.14 These findings support the use of direct infarct angioplasty in all patients presenting with cardiogenic shock, large infarctions, or anterior infarctions. The more striking improvement in left ventricular function in patients with anterior rather than inferior infarcts was likely due to the tendency for left anterior descending coronary-related infarctions to involve larger amounts of myocardium than right or left circumflex coronary-related infarctions.16 Infarct vessel reperfusion rates were similar in all three coronary arteries and thus did not account for the greater improvement in systolic function in anterior infarctions. The degree of myocardial salvage afforded patients treated with direct angioplasty in this series is consistent with that found in previous reports.8, l3 These improvements in left ventricular function are similar to the myocardial salvage documented in recent thrombolytic therapy trials,16-l8 although differing patient populations and study designs preclude direct comparisons. Randomized trials comparing direct coronary angioplasty without antecedent throm-

6

O’Keefe et al.

bolysis to thrombolytic therapy with “watchful waiting” are currently in progress and will address the issue of comparitive myocardial salvage. The improvement in left ventricular function was greatest when reperfusion was accomplished within 1 hour of pain onset, and least when over 6 hours elapsed from pain onset to infarct vessel recanalization (Fig. 2). However, the overall correlation between ischemic time and ejection fraction improvement did not achieve statistical significance. Furthermore, significant myocardial salvage was demonstrable even in patients treated between 6 and 24 hours postinfarction. Similar findings have been reported using technetium-99m-sestamibi to assess myocardial salvage. Gibbons et al.rg found the degree of myocardial salvage afforded by acute reperfusion therapy (thrombolysis or direct infarct angioplasty) highly unpredictable and not correlated with ischemic time. Reocclusion of the infarcted vessel remains a serious problem with both infarct angioplasty and intravenous thrombolytic therapy.6, 7In the current series, 11% of patients demonstrated reocclusion of the infarct artery. Any initial myocardial salvage afforded by direct angioplasty was negated by early reocclusion. These findings emphasize the importance of ongoing research to prevent and detect infarct vessel reocclusion after interventional therapy.

7.

8.

9.

10.

11.

12.

13.

14.

15. REFERENCES

1. Multicenter Postinfarction Research Group. Risk stratification and survival after msocardial infarction. N Engl J Med 1983;309:331-6. 2. Sanz G, Castaner A, Betriu A, Magrina J, Roig E, Co11 S, Pare JC. Navarro-Lonez F. Determinants of prognosis in survivors of myocardial infarction: a prospective-clinical angiographic study. N Engl J Med 1982;306:1064-70. 3. DeFeyter PJ, van Eenige MJ, Dighton DH, Visser FC, de Jong J, Roos JP. Prognostic value of exercise testing, coronary angiography and left ventriculography 6-8 weeks after myocardial infarction. Circulation 1982;66:527-36. 4. Kennedy JW, Ritchie JL, Davis KB, Stadius ML, Maynard C, Fritz JK. The Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1985;312:1073-8. 5. Gruppo Italian0 per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397-401. Study of Infarct Survival) Col6. ISIS-2 (Second International laborative Group. Randomised trial of intravenous streptoki-

16.

11.

18.

19.

nase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:34960. G’Keefe JH Jr, Rutherford BD, McConahay DR, Ligon RW, Johnson WL. Giorei LV. Crockett JE. McCallister BD. Conn RD, Gura GM, Giod TH, Steinhaus DM, Bateman TM, Shimshak TM, Hartzler GO. Early and late results of coronary angioplasty without antecedent thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1989;64:1221-30. Rothbaum DA, Linnemeier TJ, Landin RJ, Steinmetz EF, Hillis JS. Hallm CC. Noble RJ. See MR. Emereencv oercutaneous transluminal coronary angioplasty in acute myocardial infarction: a 3-year experience. J Am Co11 Cardiol1987;10:26472. Miller PF, Brodie BR, Weintraub RA, LeBauer EJ, Katz JD, Stuckey TD, Hansen DJ. Emergency coronary angioplasty for acute myocardial infarction. Results from a community hospital. Arch Intern Med 1987;147:1565-70. Stone GW, Rutherford BD, McConahay DR, Johnson WL, Giorgi LV, Ligon RW, Hartzler GO. Direct coronary angioplasty in acute myocardial infarction: outcome in patients with single-vessel disease. J Am Co11 Cardiol 1990;15:534-43. Marco J, et al. Emergency percutaneous transluminal coronary angioplastv without thrombolysis as initial therapy in acute myocardial infarction. Int J dardiol 1987;15:55-6% Ellis SG. G’Neill WW. Bates ER. Walton JA. Nabel EG. Werns SW, Top01 EJ. Implications for patient triage from survival and left ventricular functional recovery: analyses in 500 patients treated with coronary angioplasty for acute myocardial infarction. J Am Co11 Cardiol 1989;13:1251-9. O’Neill W, Timmis GC, Bourdillon PD, Lai P, Ganghadarhan V, Walton J Jr, Ramos R, Laufer NS, Gordon S, Schork MA. A prospective randomized clinical trial of intracoronary streptokinase vs coronary angioplasty for acute myocardial infarction. N Engl J Med 1986;314:812-8. Karalis DG, Parris TM. Coronary angioplasty in cardiogenic shock: a bridge to coronary artery surgery. J Invasive Cardiol 1989;1:231-7. Gregoire J, Theroux P, Gagnon D, Arsenault A. Myocardial salvage assessed by Tc-99m sestamibi SPECT following thombolysis in acute-myocardial infarction: relative importance of the area at risk and infarct location lAbstract.1. Circulation 1990;82:111-203. White HD, Norris RM, Brown MA, Takayama M, Maslowski A. Bass NM. Ormiston JA. Whitlock T. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987; 317:850-5. O’Rourke M, Baron D, Keogh A, Kelly R, Nelson G, Barnes C, Raftos J, Graham K, Hillman K, Newman H, Healey J, Woolridge J, Rivers J, White H, Whitlock R, Norris R. Limitation of mvocardial infarction by early infusion of recombinant tissue-type plasminogen activator. Circulation 1988;77:1311-5. National Heart Foundation of Australia Coronarv Thrombolysis Group. Coronary thrombolysis and myocardial salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet 1988;1:203-7. Gibbons RJ, Christian TF, Edmunds JH, Behrenbeck T. Quantitation of myocardial salvage after acute reperfusion therapy using Tc-99m-sestamibi [Abstract]. Circulation 1990; 82:111-204.