Abstract

The resistive reserve ratio (RRR) expresses the ratio between basal and hyperemic microvascular resistance. RRR measures the vasodilatory capacity of the microcirculation. We compared RRR, index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) for predicting microvascular obstruction (MVO), myocardial hemorrhage, infarct size, and clinical outcomes, after ST-segment-elevation myocardial infarction. In the T-TIME trial (Trial of Low-Dose Adjunctive Alteplase During Primary PCI), 440 patients with acute ST-segment-elevation myocardial infarction from 11 UK hospitals were prospectively enrolled. In a subset of 144 patients, IMR, CFR, and RRR were measured post-primary percutaneous coronary intervention. MVO extent (% left ventricular mass) was determined by cardiovascular magnetic resonance imaging at 2 to 7 days. Infarct size was determined at 3 months. One-year major adverse cardiac events, heart failure hospitalizations, and all-cause death/heart failure hospitalizations were assessed. In these 144 patients (mean age, 59±11 years, 80% male), median IMR was 29.5 (interquartile range: 17.0-55.0), CFR was 1.4 (1.1-2.0), and RRR was 1.7 (1.3-2.3). MVO occurred in 41% of patients. IMR>40 was multivariably associated with more MVO (coefficient, 0.53 [95% CI, 0.05-1.02]; P=0.031), myocardial hemorrhage presence (odds ratio [OR], 3.20 [95% CI, 1.25-8.24]; P=0.016), and infarct size (coefficient, 5.05 [95% CI, 0.84-9.26]; P=0.019), independently of CFR≤2.0, RRR≤1.7, myocardial perfusion grade≤1, and Thrombolysis in Myocardial Infarction frame count. RRR was multivariably associated with MVO extent (coefficient, -0.60 [95% CI, -0.97 to -0.23]; P=0.002), myocardial hemorrhage presence (OR, 0.34 [95% CI, 0.15-0.75]; P=0.008), and infarct size (coefficient, -3.41 [95% CI, -6.76 to -0.06]; P=0.046). IMR>40 was associated with heart failure hospitalization (OR, 5.34 [95% CI, 1.80-15.81] P=0.002), major adverse cardiac events (OR, 4.46 [95% CI, 1.70-11.70] P=0.002), and all-cause death/ heart failure hospitalization (OR, 4.08 [95% CI, 1.55-10.79] P=0.005). RRR was associated with heart failure hospitalization (OR, 0.44 [95% CI, 0.19-0.99] P=0.047). CFR was not associated with infarct characteristics or clinical outcomes. In acute ST-segment-elevationl infarction, IMR and RRR, but not CFR, were associated with MVO, myocardial hemorrhage, infarct size, and clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02257294.

Highlights

  • The resistive reserve ratio (RRR) expresses the ratio between basal and hyperemic microvascular resistance

  • Invasive physiology parameters that predict microvascular obstruction and prognosis may become useful for selection of patients for adjunctive therapies during primary percutaneous coronary intervention

  • Resistive reserve ratio is a measure of the vasodilator capacity of the microcirculation, whereas index of microcirculatory resistance is a measure of the minimum achievable microvascular resistance at peak hyperemia

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Summary

Methods

In the T-TIME trial (Trial of Low-Dose Adjunctive Alteplase During Primary PCI), 440 patients with acute STsegment–elevation myocardial infarction from 11 UK hospitals were prospectively enrolled. In a subset of 144 patients, IMR, CFR, and RRR were measured post-primary percutaneous coronary intervention. The patients were enrolled into the prespecified physiology substudy of the T-TIME trial,[17] which was a double-blind randomized clinical trial of adjunctive intracoronary alteplase (10 or 20 mg) versus placebo delivered post-reperfusion, but pre-stenting, and found no difference in MVO at 2 to 7 days. Eligibility criteria (Data Supplement) included occlusion or reduced flow (Thrombolysis in Myocardial Infarction [TIMI] coronary flow grade ≤2) in the culprit artery, with thrombus evident angiographically. Witnessed verbal assent to participate was obtained in the catheterization laboratory. Written informed consent was subsequently obtained on the ward

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