Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: An important determinant of survival

Abstract

Thrombolytic therapy for acute myocardial infarction reduces early mortality, but full recovery of left ventricular function after reperfusion is delayed. Therefore, the relations among reperfusion, survival and the time course of left ventricular functional recovery were examined in 226 patients treated with intracoronary streptokinase; 77% (134 patients) had sustained reperfusion and 31 patients had no reperfusion or had reocclusion by day 3. Wall motion was measured from contrast ventriculograms performed in the acute period and 3 days later in the central and peripheral infarct regions and the noninfarct region by the centerline method in 165 patients. Patients with reperfusion had better survival (p less than 0.05, mean follow-up 4.5 years) and a higher ejection fraction at 3 days (52 +/- 12 versus 46 +/- 10%, p less than 0.02) attributable to a significantly different change in peripheral infarct region function between the acute and 3 day studies (0.1 +/- 1.0 versus -0.3 +/- 0.9 SD, p less than 0.05). These early functional changes were significant in patients with anterior myocardial infarction and showed similar trends in those with inferior myocardial infarction. On Cox regression analysis, function measured at 3 days was more predictive of survival than was function measured acutely (chi square for acute ejection fraction = 11.48 versus 24.59 at 3 days). Although, as previously reported, greater than 45% of total recovery of left ventricular function occurs later, the ejection fraction achieved by day 3 is already predictive of survival. Thus, the mechanism by which successful thrombolytic therapy enhances survival is improvement of regional and global left ventricular function early after acute myocardial infarction.

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

“…Improvement in ventricular function occurred gradually over the course of a few weeks. [81][82][83][84] One report 85 suggested that stunned myocardium could be recruited after thrombolytic therapy with small boluses of inotropes. These studies suggest that the ultimate return of cardiac function cannot be determined immediately after reperfusion.…”

Potential benefits of late reperfusion of infarcted myocardium. The open artery hypothesis.

“…Early in the thrombolytic era, it became clear that, as had been observed in the case of myocardial salvage in the canine model, benefit was greatest when such therapy was initiated within 1 hour of symptom onset. 8,10,13,15 As originally conceived, thrombolytic therapy was intended to interrupt the progression from myocardial ischemia to necrosis that resulted from occlusion of the infarct-related artery (IRA) (Fig 1) [19][20][21] This modest improvement in LVEF induced by reperfusion is due to the preservation of regional myocardial function in the distribution of the IRA. 21 Like patient survival, the extent to which thrombolysis preserves left ventricular function depends on the time interval between the onset of symptoms and commencement of treatment.…”

“…8,10,13,15 As originally conceived, thrombolytic therapy was intended to interrupt the progression from myocardial ischemia to necrosis that resulted from occlusion of the infarct-related artery (IRA) (Fig 1) [19][20][21] This modest improvement in LVEF induced by reperfusion is due to the preservation of regional myocardial function in the distribution of the IRA. 21 Like patient survival, the extent to which thrombolysis preserves left ventricular function depends on the time interval between the onset of symptoms and commencement of treatment. [19][20][21][22][23][24][25] The sequence described above, ie, early reperfusion of an occluded IRA -* myocardial salvage --preservation of regional function --preservation of global left ventricular function -> improved patient survival, is supported by many experimental and clinical studies and has become so widely accepted that it could be called a "paradigm."…”

“…21 Like patient survival, the extent to which thrombolysis preserves left ventricular function depends on the time interval between the onset of symptoms and commencement of treatment. [19][20][21][22][23][24][25] The sequence described above, ie, early reperfusion of an occluded IRA -* myocardial salvage --preservation of regional function --preservation of global left ventricular function -> improved patient survival, is supported by many experimental and clinical studies and has become so widely accepted that it could be called a "paradigm." A key aspect of this paradigm is that the time of opening of the IRA is of central importance to the benefit achieved.…”

Prognostic implications and predictors of enhanced regional wall motion of the noninfarct zone after thrombolysis and angioplasty therapy of acute myocardial infarction. The TAMI Study Groups.

“…Early assessment of regional function within the infarct zone appears to be of limited clinical value10U11; however, function of the noninfarct zone may be predictive of hemodynamic status12 and survival. 10,13 Likewise, the presence of multivessel coronary disease has been associated with a high mortality after acute myocardial infarction.14 Whether this increased mortality is due to large infarction size, suppression of compensatory hyperkinesis in the noninfarct zone, or a combination of these factors has not been investigated. A better understanding of the pathophysiology of myocardial function remote from the infarct zone could lead to strategies enabling maximization of global ventricular function.…”