Reperfusion revisited: Beyond TIMI3 flow

Abstract

Summary: Therapy for acute myocardial infarction has advanced dramatically since the early 1980s with the use of early intravenous fibrinolytic therapy. Combining low-dose fibrinolysis and platelet lysis appears to provide an additional increase in infarct-related artery (IRA) patency, but the largescale mortality reduction trials evaluating this strategy are just getting under way. Recently, considerable attention has shifted away from the epicardial arteries to the microvasculature. Contemporary evidence suggests that epicardial patency does not necessarily translate to actual perfusion at the myocardial level. Techniques to evaluate beyond thrombolysis in myocardial infarction (TIMI) epicardial flow are now available and validated. In addition, there are promising treatments for the prevention or alleviation of certain forms of microvascular obstruction. This review attempts to clarify the confusion surrounding epicardial flow and "myocardial malperfusion" and to provide some insight into the next direction in acute myocardial infarction therapeutics.

Microemboli and Microvascular Obstruction in Acute Coronary Thrombosis and Sudden Coronary Death

“…Importantly, microemboli and MVO may both occur even when the epicardial coronary arteries are widely patent with excellent angiographic flow (7). Cardiac magnetic resonance imaging detects MVO, and has found it associated with slow myocardial flow and the "no-reflow" phenomenon after coronary intervention (8).…”

Admission Troponin T Level Predicts Clinical Outcomes, TIMI Flow, and Myocardial Tissue Perfusion After Primary Percutaneous Intervention for Acute ST-Segment Elevation Myocardial Infarction

“…[2][3][4] In clinical practice, however, assessment of microvascular dysfunction is frequently retrospective, and available techniques are difficult to apply. 5 Thus, the cTnT status on admission may aid in the selection of patients in whom adjunctive therapies that are targeted to improve epicardial and microvascular flow, such as coronary stenting or GP IIb/IIIa antagonists, are warranted. Values given as medians with interquartile range in parentheses unless indicated otherwise.…”

“…5 In our study, microvascular perfusion was assessed by means of ST-segment resolution on serial ECG and by measurement of early marker increases. Analysis of ST segments is established for noninvasive estimation of reperfusion success after thrombolytic therapy 22,23 but is less well documented after PCI.…”

“…Diagnostic tests for identification of microvascular dysfunction, such as coronary Doppler flow wire, myocardial contrast echocardiography, MRI, and 99m Tc sestamibi single photon emission CT, however, are still investigational and not widely available. 5 Recently, several clinical studies found that elevated troponins on admission predicted worse short-and long-term prognosis and higher rates of failed thrombolytic therapy or primary PCI in patients with ST-segment elevation myocardial infarction. 6 -10 The exact reason why a positive troponin on admission may be linked to a worse outcome is unsettled but may involve more extensive tissue damage due to longer periods of preinterventional myocardial ischemia, a lower success rate of reperfusion, and microvascular dysfunction.…”

Myocardial Perfusion Imaging Using Contrast Echocardiography

“…Myocardial malperfusion can be the result of a number of mechanisms operating during the perirecanalization period. Showers of microemboli, formation of microthrombi, microvascular spasm, and reperfusion injury caused by oxygen free radicals, neutrophil plugging of capillaries, and tissue edema could singly or in combination lead to myocardial malperfusion [12]. Serial myocardial contrast echocardiography yields valuable physiologic insights on the integrity and behavior of the microvasculature in the risk area and yields prognostic data.…”