Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment-Elevation Myocardial Infarction

David Carrick, Caroline Haig, Nadeem Ahmed, Jaclyn Carberry, Vannesa Teng Yue May, Margaret McEntegart, Mark C Petrie, Hany Eteiba, Mitchell Lindsay, Stuart Hood, Stuart Watkins, Andrew Davie, Ahmed Mahrous, Ify Mordi, Ian Ford, Aleksandra Radjenovic, Keith G Oldroyd, Colin Berry, David Carrick, Caroline Haig, Nadeem Ahmed, Jaclyn Carberry, Vannesa Teng Yue May, Margaret McEntegart, Mark C Petrie, Hany Eteiba, Mitchell Lindsay, Stuart Hood, Stuart Watkins, Andrew Davie, Ahmed Mahrous, Ify Mordi, Ian Ford, Aleksandra Radjenovic, Keith G Oldroyd, Colin Berry

Abstract

Background: Primary percutaneous coronary intervention is frequently successful at restoring coronary artery blood flow in patients with acute ST-segment-elevation myocardial infarction; however, failed myocardial reperfusion commonly passes undetected in up to half of these patients. The index of microvascular resistance (IMR) is a novel invasive measure of coronary microvascular function. We aimed to investigate the pathological and prognostic significance of an IMR>40, alone or in combination with a coronary flow reserve (CFR≤2.0), in the culprit artery after emergency percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction.

Methods: Patients with acute ST-segment-elevation myocardial infarction were prospectively enrolled during emergency percutaneous coronary intervention and categorized according to IMR (≤40 or >40) and CFR (≤2.0 or >2.0). Cardiac magnetic resonance imaging was acquired 2 days and 6 months after myocardial infarction. All-cause death or first heart failure hospitalization was a prespecified outcome (median follow-up, 845 days).

Results: IMR and CFR were measured in the culprit artery at the end of percutaneous coronary intervention in 283 patients with ST-segment-elevation myocardial infarction (mean±SD age, 60±12 years; 73% male). The median IMR and CFR were 25 (interquartile range, 15-48) and 1.6 (interquartile range, 1.1-2.1), respectively. An IMR>40 was a multivariable associate of myocardial hemorrhage (odds ratio, 2.10; 95% confidence interval, 1.03-4.27; P=0.042). An IMR>40 was closely associated with microvascular obstruction. Symptom-to-reperfusion time, TIMI (Thrombolysis in Myocardial Infarction) blush grade, and no (≤30%) ST-segment resolution were not associated with these pathologies. An IMR>40 was a multivariable associate of the changes in left ventricular ejection fraction (coefficient, -2.12; 95% confidence interval, -4.02 to -0.23; P=0.028) and left ventricular end-diastolic volume (coefficient, 7.85; 95% confidence interval, 0.41-15.29; P=0.039) at 6 months independently of infarct size. An IMR>40 (odds ratio, 4.36; 95% confidence interval, 2.10-9.06; P<0.001) was a multivariable associate of all-cause death or heart failure. Compared with an IMR>40, the combination of IMR>40 and CFR≤2.0 did not have incremental prognostic value.

Conclusions: An IMR>40 is a multivariable associate of left ventricular and clinical outcomes after ST-segment-elevation myocardial infarction independently of the infarction size. Compared with standard clinical measures of the efficacy of myocardial reperfusion, including the ischemic time, ST-segment elevation, angiographic blush grade, and CFR, IMR has superior clinical value for risk stratification and may be considered a reference test for failed myocardial reperfusion.

Clinical trial registration: URL: https//www.clinicaltrials.gov. Unique identifier: NCT02072850.

Keywords: magnetic resonance imaging; microcirculation; myocardial infarction; prognosis.

© 2016 The Authors.

Figures

Figure 1.
Figure 1.
Four patients with acute ST-segment–elevation myocardial infarctiontreated by primary percutaneous coronary intervention (PCI). Each patient had index of microvascular resistance (IMR) and coronary flow reserve (CFR) measured in the culprit coronary artery at the end of the procedure. The patients reflect the following categories: IMR≤40 and CFR>2.0; IMR≤40 and CFR≤2.0; IMR>40 and CFR>2.0; and IMR>40 and CFR≤2.0. The patients were treated with similar antithrombotic therapy, including aspirin, clopidogrel, heparin, and intravenous glycoprotein IIb/IIIa inhibitor therapy with tirofiban. Each patient had normal TIMI (Thrombolysis in Myocardial Infarction) grade 3 flow at the end of PCI. Cardiac magnetic resonance imaging (MRI) was performed for each patient 2 days later. A, A patient with a normal IMR and a normal CFR. Invasive assessment of microvascular function in the culprit coronary artery at the end of primary PCI indicated that microcirculatory function was preserved. Cardiac magnetic resonance (CMR) subsequently revealed nontransmural late gadolinium enhancement consistent with salvaged myocardium. There was no evidence of myocardial hemorrhage (middle right) or microvascular obstruction (right). B, A patient with a normal IMR and a low CFR. Late gadolinium contrast CMR revealed transmural inferior myocardial infarction with a small central zone of hypointense microvascular obstruction (arrow, right). T2*-CMR excluded myocardial hemorrhage within the infarct core (middle right). C, A patient with a high IMR and a normal CFR. Late gadolinium contrast-enhanced CMR revealed transmural anteroseptal myocardial infarction complicated by microvascular obstruction (arrow, right). T2*-CMR (arrow, middle right) revealed myocardial hemorrhage within the infarct core, and microvascular obstruction spatially corresponded with the myocardial hemorrhage. D, A patient with a high IMR and a low CFR. Invasive guidewire-based physiological testing at the end of primary PCI revealed severe microvascular dysfunction. Transmural myocardial infarction and microvascular obstruction are present, in association with abundant myocardial hemorrhage (arrow, middle right).
Figure 2.
Figure 2.
CONSORT (Consolidated Standards of Reporting Trials) flow diagram of the cohort study. CFR indicates coronary flow reserve; CMR, cardiac magnetic resonance; IMR, index of microvascular resistance; and STEMI, ST-segment–elevation myocardial infarction.

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