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Update on mechanical intervention in acute myocardial infarction

The role of pharmacologic interventions in acute myocardial infarction (i.e., a combination of intravenous nitroglycerin, intravenous @-blocker, oral aspirin, and intravenous thrombolysis), has become more standardized, whereas the role of mechanical intervention remains to be defined. Mechanical intervention includes percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting. The number of carefully controlled, randomized trials is limited, particularly with surgery. Nevertheless, in optimal circumstances, when performed within the first few hours of myocardial infarction, surgery can be beneficial in reducing mortality, especially with anterior location of infarct. Surgery may not prevent reinfarctlon. However, the results of nonrandomized surgical trials done 10 years ago are difficult to compare with modern-day treatment of myocardial infarction with the availability of new agents and PTCA. Angloplasty can be performed safely in the acute phase of myocardial infarction but may not be the ideal choice for all patients. The results may be more optimal if performed when the patient is stable. Clinical factors associated with favorable and unfavorable outcomes have been identified. Mortality is not significantly affected by early versus late PTCA. Certain selected patients benefit from PTCA, particularly those in cardiogenic shock, in whom PTCA has made a dramatic improvement in outcome. To achieve maximal benefit, intervention should be performed early, within the first hours of symptoms. Further well-designed studies may help clarify the role mechanical techniques will play in future combinations of interventional therapy. (AM HEART J (1990;120:734.)

Stephen C. Vlay, MD. Stony Brook, A? Y.

The number of therapeutic options for the treatment of acute myocardial infarction has increased greatly during the past decade and now includes mechanical and surgical interventions-percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG)-as well as medical treatments. Few cardiologists today would hesitate to initiate individual or combination therapy with intravenous nitroglycerin, aspirin, intravenous meto- prolol, or thrombolysis in the “typical” patient with myocardial infarction meeting the standard criteria and having no contraindications to these treatments. However, the role of coronary angioplasty and bypass surgery is more controversial, as was the role of P-blockers and thrombolysis just a short time ago. The comparative efficacy of surgical and medical treatments continues to be assessed in large-scale studies, the results of which will form the basis for treatment recommendations. Of particular interest is

From the Division of Cardiology, Department of Medicine, State University of New York Health Sciences Center, Stony Brook.

Reprint requests: Stephen C. Vlay, MD, Associate Professor of Medicine and Director, CCU, Health Sciences Center T-17 020, SUNY at Stony Brook, Stony Brook, NY 11794-8171.

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whether the timing of surgical intervention or PTCA (acute or elective) affects the outcome in specific subsets of the myocardial infarction population. This article presents current views on the role of mechanical interventions in the treatment of acute myocardial infarction.

ROLE OF SURGERY (CABG)

Some insights into the comparative efficacy of CABG versus medical management may be gained by reviewing the results of a long-term study conducted in Spokane, Wash. 1, 2 This investigation involved 387 patients with myocardial infarction managed either medically or surgically who were followed for up to 13 years. Baseline variables, such as age, gender, infarct location, number of diseased vessels, and Killip clas- sification, were comparable between the two groups.

Overall mortality. The in-hospital mortality rate was 5.8% in the surgical group and 11.5% in the medical group (p < 0.07). Long-term mortality rates (assessed at 10 to 13 years) were 27 % and 41% , respectively (p < 0.0007). In both instances, the differences between the two groups were highly statistically significant. In addition, the surgical and medical groups had significantly different rates of sudden cardiac

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death-7.4% versus 17.5%) respectively (p < 0.01). The mortality data were also analyzed according to

whether CABG was performed early (within 6 hours of symptom onset) or late (after 6 hours). The results revealed that patients who underwent surgery during the late phase of acute myocardial infarction had a mortality rate similar to that in the medically managed group. On the other hand, the mortality rate was only 2% among patients who underwent CABG within the first 2 hours. These data suggest that outcome can be improved if intervention is accomplished early in the course of myocardial infarction and if the infarct-related artery is successfully opened.

Reinfarction rates. The analysis of reinfarction rates revealed no significant difference between the medical and surgical groups. This confirms the well- established observation that CABG does not prevent myocardial infarction. Among only subjects who experienced recurrent myocardial infarction, the mortality rate was lower in the surgical arm of the study (p = 0.04). One explanation for the latter finding may be that surgery afforded more complete revascular- ization of vessels other than the infarct-related artery and thereby protected a greater area of myocardium.

Anterior versus inferior wall infarction. Analysis by location of infarction showed that mortality was significantly greater among patients with large amounts of jeopardized myocardium who were initially treated medically. The mortality rate was 50% among patients with anterior wall Q wave infarctions compared with 3% among those with inferior wall infarctions.

Anterior wall infarction. In patients with anterior wall infarctions, surgical therapy was associated with a better outcome in both in-hospital mortality and 13-year mortality. In addition, whether surgery was performed early or late made a significant difference. The 13-year mortality rate was 30% for patients receiving early surgical intervention compared with 54% for patients treated medically (p = 0.0006).

Global ejection fraction was higher by 7 % to 10 % in patients receiving surgery than in patients treated medically. The ejection fraction was not significantly different in patients receiving early versus late surgical intervention.

Inferior wall infarction. Overall in-hospital mortality was not significantly different for patients with inferior wall infarctions treated medically or surgically (6.1% vs 4.6%), nor was there a significant difference overall between the medical and surgical treatment groups in 13-year mortality. However, the Xl-year mortality rate was greatly affected by the timing of surgery; it was 19% for patients treated

with early surgery and 47% for late surgery, compared with a 32% mortality rate in the medical treatment group. In-hospital mortality was not as dramatically affected by early or late surgery.

The benefit of early surgery in the patients with inferior wall infarctions was also seen in the ejection fraction, which was 56% for patients treated with early surgery compared with 47 % for those receiving medical treatment (p < 0.01).

Clinical implications. The results of this study suggest that surgical intervention may offer benefit in a specific subset of patients with acute myocardial infarction. One must keep in mind, however, that these data were collected in 1979 before many of the cur- rently available medical therapies (most notably, thrombolysis) had been introduced. Consequently, the results cannot be extrapolated to the present medical armamentarium. A further consideration is the fact that this investigation was nonrandomized and uncontrolled. In light of these limitations, one may conclude that CABG may be performed safely and may substantially improve outcome but only in a carefully selected segment of the myocardial infarction population.

ROLE OF ANGIOPLASTY (PTCA)

Over the past few years, several major studies have attested to the fact that PTCA can be performed safely and successfully during the acute phase of myocardial infarction. Various studies have compared outcomes from immediate and delayed PTCA and have evaluated the use of PTCA in conjunction with thrombolytic therapy and in special patient groups. Study end points include reocclusion and reinfarction as well as mortality.

Efficacy and mortality with PTCA. In a 1988 Duke University study, PTCA resulted in successful reperfusion of the infarct-related artery in 94% of 342 patients.3 The procedure-related mortality rate was low (1.2 % ), and the in-hospital mortality rate (11% ) was similar to that which would be expected with medical management. The l-year survival rate was 87% among the overall study population and was 98% among patients who survived the hospitalization period. In addition, 84 % of patients had a l-year survival free of cardiac events, and 94 % experienced a l-year infarct-free survival.

Information on longer-term outcome emerged from work conducted at the University of Michigan in Ann Arbor. When performed within 4 hours of onset of symptoms, PTCA was associated with an in-hospital mortality rate of 11%.4 Among 293 patients (mean age, 55 years) who survived the hospitalization phase, the mean ejection fraction was 48%) multiple-vessel

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disease was present in 53 % , and half had received thrombolytic therapy in addition to angioplasty. The l-year survival rate in this group was 96 % , and the 2-year survival rate was 94%.

Predictors of successful PTCA. A study reported by Ellis et a1.5 examined the results of PTCA in terms of factors that were associated with a favorable or unfavorable outcome. In this study population of mid- dle-aged men, 6 % of the patients were in cardiogenic shock. The mean ejection fraction was 46 % . The angioplasty procedure was associated with a success rate of 80%) which was slightly lower than in other University of Michigan studies.

Several factors were judged to be predictive of a favorable outcome: ejection fraction >30 % , absence of anatomical features that might complicate the procedure (such as an arterial bend at the PTCA site), fewer than three diseased vessels, absence of total occlusion, and absence of additional stenoses. Angioplasty should be avoided if there is well-main- tained coronary flow and no reason to expect immediate reocclusion.

Features associated with a poor prognosis included the presence of coronary flow classified as less than TIM1 grade 1 or more than two risk factors for PTCA failure (i.e., poor ejection fraction, a bend at the pro- posed dilation site, or triple-vessel disease). When these factors are present, bypass surgery may be considered, if the patient is an otherwise suitable surgical candidate.

Acute versus elective PTCA. In a follow-up of patients in a Duke University study who underwent PTCA on an acute or elective basis,6 the in-hospital reocclusion rate was notably higher when PTCA was performed in the acute phase than when it was done on an elective basis (p < O.OOOl), whereas late restenosis (at 28 to 30 weeks) was slightly more com- mon after the elective procedure (p < 0.0006).

PTCA after thrombolysis. The results of two large studies analyzing the use of PTCA in patients treated with tissue plasminogen activator (tPA) have greatly influenced trends in the management of patients with myocardial infarction. One of these was the Throm- bolysis and Angioplasty in Myocardial Infarction (TAMI) trial.7 Of the 386 patients treated, 288 were successfully reperfused by way of thrombolysis with tPA, 197 of whom were suitable candidates for PTCA. This latter group was randomized to undergo angioplasty either immediately or 7 to 10 days after admission to the hospital.

The reocclusion rates associated with immediate and delayed PTCA were 11% and 13 % , respectively, a difference that was not statistically significant. Neither group experienced a significant improve-

ment in left ventricular ejection fraction. Emergency PTCA was required in 16% of the patients who had been randomized to the elective procedure and in 5 % of those randomized to the immediate procedure. Among those assigned to delayed PTCA, 14% were judged not to require the procedure when they were reassessed at 7 to 10 days, probably because their thrombi had largely resolved. On the basis of these findings, the study team concluded that immediate angioplasty in the acute phase of myocardial infarction offers no clear advantage over delayed angioplasty.

Some observers have criticized this study because of the fact that the 96 patients who failed thrombolysis were not randomized. The investigators nonetheless attempted immediate angioplasty in 86 of these individuals.’ Angioplasty was successful (defined as <50 % residu,al stenosis) in 73 % and failed to open the infarct-related artery in 11% . A high-grade residual stenosis was observed in 16%. These data demonstrated that PTCA is capable of opening the infarct-related artery in most patients who fail thrombolysis. However, the in-hospital reocclusion rate was relatively high, 29%) despite therapy with heparin and aspirin, which indicates that such arteries are severely diseased initially. No significant improvement was seen in either regional or global left ventricular function. In view of these limitations, the investigators concluded that PTCA does not offer important benefit in patients who fail thrombolytic therapy. (Still, there was a considerable difference in mortality, 6 % after successful angioplasty and 44 % after a failed procedure.)

Similar conclusions emerged from the Thrombol- ysis in Myocardial Infarction (TIMI) trial,g which examined the use of immediate versus delayed angioplasty after the administration of tPA. The success rate was 84% with immediate PTCA and 93% with the delayed procedure, but no significant difference was apparent in left ventricular ejection fraction. Immediate PTCA was associated with a greater need for acute surgery as well as a higher risk of bleeding.

The European Cooperative Study GrouplO compared the results of immediate versus no angioplasty in a group of patients with myocardial infarction who received tPA plus aspirin and heparin. The results showed that PTCA reduced the percentage of stenosis but was associated with a high rate of transient as well as sustained reocclusion. Furthermore, a 17% incidence of recurrent ischemia was noted during the first 24 hours. The 14-day mortality rate was 7% in the PTCA group compared with 3 % in a group managed noninvasively. No significant between-group

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differences were apparent with regard to infarct size or left ventricular ejection fraction.

In a 1989 report on a German study, Erbel et al.‘l described findings in patients who received intra- coronary streptokinase either alone or followed by immediate PTCA. The combined approach yielded an overall success rate of 69%; 9% of patients required repeat angioplasty, which was successful in 100% of cases. Among the patients treated with streptokinase alone, 21% required elective PTCA, which was successful in 86%. The incidence of reocclusion and reinfarction and the 3-year mortality rate were similar in the two groups, again suggesting that immediate angioplasty is not warranted in most patients treated with thrombolytic therapy.

In yet another investigation at the University of Michigan, early PTCA was associated with a success rate of 73% in patients who had received thrombolytic therapy; half this group had anterior wall infarctions.12

In summary, the cumulative experience from these many trials has demonstrated several factors that correlate with in-hospital mortality associated with PTCA, specifically, ejection fraction of <30 % , failure to open the artery, and advanced age of the patient. In addition, recurrent ischemia after PTCA, devel- opment of hypotension during catheterization, and the need for emergency surgery were associated with adverse outcomes.

The patients who benefit most from immediate angioplasty are those in cardiogenic shock or having anterior wall infarctions. Many such patients would die if left untreated. One study from the University of Michigan focused specifically on 87 patients who presented with cardiogenic shock.13 Of this group, 59 % received standard medical therapy and 24% underwent PTCA. At 30 days, the overall survival rate was 50% in the PTCA group and 17 % in the group treated medically. However, among patients in whom angioplasty was successful, survival was 77 % . As expected, the survival rate in patients in whom angioplasty failed was comparable with that observed with medical therapy alone. Nonetheless, the 77% survival rate is a tremendous improvement in outcome for such high-risk patients.

Elderly patients have generally not been considered good candidates for thrombolytic therapy, al- though some of the more recent studies have indicated that this population stands to benefit from such intervention. In a group of 35 patients older than 70 years of age, half of whom had received thrombolytic therapy, angioplasty was found to be successful in 74% of cases.14 Failure to open the infarct-related artery resulted in a mortality rate of 73%, whereas

the presence of a patent artery was associated with a mortality rate of 19 %-a difference that was highly statistically significant 0, = 0.003). The reocclusion rate was 15 % .

When these results are compared with those of a population of 200 patients younger than 70 years of age, it becomes apparent that older patients experience a lesser degree of primary success and a higher in-hospital mortality rate after emergency PTCA. In interpreting these results, however, one must keep in mind that elderly patients with myocardial infarction are likely to be at higher risk from the outset.

PTCA as a primary modality. The use of PTCA as a primary treatment modality (in place of P-blockers, nitrates, or thrombolysis) was explored in a study of 139 patients with myocardial infarction.15 When performed within 15 hours of onset of symptoms, angioplasty was successful in 78 % of cases. The in-hospital mortality rate was 5.5 % after successful PTCA and 43% after failed procedures; this difference was highly statistically significant 0, < 0.001). Results such as these demonstrate that the use of immediate angioplasty as a sole intervention is feasible, but they do not indicate that this approach is appropriate for all patients.

CONCLUSIONS

At present, the role of CABG in the management of acute myocardial infarction remains unclear. More studies will be needed to determine whether surgery might improve outcomes in specific subsets of patients, such as those who fail thrombolysis or have contraindications to angioplasty. In all likelihood, however, many patients with acute myocardial infarction who are not candidates for PTCA will like- wise be unsuitable for CABG. Furthermore, surgery must be accomplished within 6 hours of the onset of symptoms if optimal benefits are to be realized.

The data gathered thus far suggest that immediate angioplasty is indicated in patients whose condition is deteriorating because of ongoing ischemia or infarction, which may result in cardiogenic shock and death. Angioplasty may possibly be lifesaving in these patients. Acute angioplasty does not appear to offer any advantage over delayed angioplasty in patients who are relatively stable but continue to experience ischemia. In some patients, intervention is de- sirable, but thrombolysis is contraindicated. Angio- plasty may also be considered in these patients, but one must remember that anticoagulation is usually an adjunct to angioplasty for the first 24 hours.

Acute angioplasty for myocardial infarction is associated with a fairly high rate of early reocclusion, ranging from 13 % to 16 % and up to 25 % in some se-

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ries. The rate is higher in the elderly. The procedure carries a low mortality rate but is associated with some risk of complications, such as hypotension, ventricular fibrillation, bleeding, and the need for urgent surgery.

Patients do benefit from the present standard treatment for acute myocardial infarction, which includes oxygen, morphine, sedation, and drug therapy with nitroglycerin, aspirin, P-blockers, and thrombolytic agents. Mechanical intervention cannot be considered until a patient with hemodynamic com- promise has been stabilized. There is no question that mechanical interventions are of benefit in certain patients. The problem in evaluating the results of the existing studies is that these trials included no control groups, and the therapies were not standardized. Many of the PTCA trials involved carefully selected patients who were evaluated and treated by highly skilled and experienced angiographers. In such hands, angioplasty may be successful even as primary therapy for acute myocardial infarction. Nevertheless, the results of such studies may not be applicable to the entire myocardial infarction population. Nonetheless, it is clear that to be successful, mechanical interventions must be done early, within the first few hours of the onset of symptoms. Further well-designed controlled studies are needed to help clarify the conditions under which these procedures will produce favorable or unfavorable outcomes to gain the maximum possible benefit from their use.

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