Comparative Significance of Invasive Measures of Microvascular Injury in Acute Myocardial Infarction

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: heart failure; hospitalization; magnetic resonance imaging; microcirculation; myocardial infarction.

Figure 1.

Flow of subjects through the study. CFR indicates coronary flow reserve; CMR, cardiovascular magnetic resonance; IMR, index of microcirculatory resistance; MVO, microvascular obstruction; PCI, percutaneous coronary intervention; RRR, resistive reserve ratio; and STEMI, ST-segment–elevation myocardial infarction.

Figure 2.

Scatterplots showing correlations between coronary physiology parameters. The following correlations are shown: (A) coronary flow reserve (CFR) and resistive reserve ratio (RRR); (B) index of microcirculatory resistance (IMR) and CFR; and (C) RRR and IMR. Also shown is discordance between dichotomized coronary physiology parameters and presence/absence of microvascular obstruction.

Figure 3.

DeLong comparisons of receiver operating characteristic curves, showing performance of index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). The predictive ability of IMR, CFR and RRR are shown for the following: (A) microvascular obstruction (MVO) presence/absence; (B) myocardial hemorrhage presence/absence; (C) hospitalization for heart failure; and (D) major adverse cardiac events.