Effects of Intracoronary Alteplase on Microvascular Function in Acute Myocardial Infarction

Abstract

Background--Impaired microcirculatory reperfusion worsens prognosis following acute ST-segment-elevation myocardial infarction. In the T-TIME (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI) trial, microvascular obstruction on cardiovascular magnetic resonance imaging did not differ with adjunctive, low-dose, intracoronary alteplase (10 or 20 mg) versus placebo during primary percutaneous coronary intervention. We evaluated the effects of intracoronary alteplase, during primary percutaneous coronary intervention, on the index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio.Methods and Results--A prespecified physiology substudy of the T-TIME trial. From 2016 to 2017, patients with ST-segmentelevation myocardial infarction ≤6 hours from symptom onset were randomized in a double-blind study to receive alteplase 20 mg, alteplase 10 mg, or placebo infused into the culprit artery postreperfusion, but prestenting. Index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were measured after percutaneous coronary intervention. Cardiovascular magnetic resonance was performed at 2 to 7 days and 3 months. Analyses in relation to ischemic time (<2, 2-4, and ≥4 hours) were prespecified. One hundred forty-four patients (mean age, 59AE11 years; 80% male) were prospectively enrolled, representing 33% of the overall population (n=440). Overall, index of microcirculatory resistance (median, 29.5; interquartile range, 17.0-55.0), coronary flow reserve(1.4 [1.1-2.0]), and resistive reserve ratio (1.7 [1.3-2.3]) at the end of percutaneous coronary intervention did not differ between treatment groups. Interactions were observed between ischemic time and alteplase for coronary flow reserve (P=0.013), resistive reserve ratio (P=0.026), and microvascular obstruction (P=0.022), but not index of microcirculatory resistance.Conclusions--In ST-segment-elevation myocardial infarction with ischemic time ≤6 hours, there was overall no difference in microvascular function with alteplase versus placebo.

Long-Term Clinical Outcomes in Patients With an Acute ST-Segment-Elevation Myocardial Infarction Stratified by Angiography-Derived Index of Microcirculatory Resistance

“…As a confirmation of this hypothesis, in our cohort, the median value of RRR—a dedicated index to express the vasodilatory capacity of the coronary microcirculation—was 1.7. This value is suggestive of a depressed coronary microvascular vasodilatory capacity in this cohort of patients with STEMI, a finding consistent with previous reports ( 12 , 13 ). This depressed vasodilatory capacity can explain why, particularly in patients with STEMI, a non-hyperaemic index such as NH IMR angio retains some diagnostic accuracy in identifying microvascular injury ( 14 ).…”

“…It is reported that in most patients with STEMI the vasodilatory capacity of the microvascular coronary bed is blunted and consequently the response of coronary microcirculation to adenosine is often minimal or incomplete. ( 12 , 13 ). In this regard, we have recently described the non-hyperaemic version of IMR angio –NH IMR angio , and shown it retains its diagnostic reliability in most patients with STEMI ( 14 ).…”

Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: A systematic review and meta‐analysis

“…The PRISMA flowchart is shown in Figure 1. After screening 2490 records, we identified 15 articles to include in our meta‐analysis 26–41 . Results for IMR stratified by the presence of MVO were available in eight included studies 15,26,27,30,31,34,36,40,41 .…”

“…32], with the mean difference in IMR of15.1 [9.7−20.6] (2). The diagnostic utility of IMR with traditional cut-off value of 40 to assess MVO was modest (sensitivity 69% and specificity 65%) based on our SROC curve analysis.…”

Machine learning assisted reflectance spectral characterisation of coronary thrombi correlates with microvascular injury in patients with ST-segment elevation acute coronary syndrome

“…Indeed, GpIIb/IIIa was predominantly (72%) used as a bailout strategy after thrombus aspiration. Nonetheless this is unlikely to confound our endpoint as insights from the T-TIME randomised trial show that intracoronary thrombolysis had no effect on microvascular injury indices ( 30 ).…”