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IMPORTANCE Percutaneous coronary intervention (PCI) of nonculprit vessels among patients with ST-segment elevation myocardial infarction (STEMI) is associated with improved clinical outcome compared with culprit vessel-only PCI. Fractional flow reserve (FFR) and coronary flow reserve are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio was introduced as a nonhyperemic alternative to FFR. Whether these indices can be used in the acute setting of STEMI continues to be investigated. OBJECTIVE To assess the value of hemodynamic indices in nonculprit vessels of patients with STEMI from the index event to 1-month follow-up. DESIGN, SETTING, AND PARTICIPANTS This substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) randomized clinical trial enrolled 98 patients with STEMI who had an angiographic intermediate stenosis in at least 1 nonculprit vessel. Patient enrollment was between May 1, 2015, and September 19, 2017.After successful primary PCI, nonculprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed from 2 to 7 days and 1 month after primary PCI. MAIN OUTCOMES AND MEASURESThe value of nonculprit instantaneous wave-free ratio, FFR, coronary flow reserve, hyperemic index of microcirculatory resistance, and resting microcirculatory resistance from the index event to 1-month follow-up. RESULTSOf 73 patients with STEMI included in the final analysis, 59 (80.8%) were male, with a mean (SD) age of 60.8 (9.9) years. Instantaneous wave-free ratio (SD) did not change significantly (0.93 [0.07] vs 0.94 [0.06]; P = .12) and there was no change in resting distal pressure/aortic pressure (mean [SD], 0.94 [0.06] vs 0.95 [0.06]; P = .25) from the acute moment to 1-month follow-up. The FFR decreased (mean [SD], 0.88 [0.07] vs 0.86 [0.09]; P = .001) whereas coronary flow reserve increased (mean [SD], 2.9 [1.4] vs 4.1 [2.2]; P < .001). Hyperemic index of microcirculatory resistance decreased and resting microcirculatory resistance increased from the acute moment to follow-up. The decrease in distal pressure from rest to hyperemia was smaller at the acute moment vs follow-up (mean [SD], 10.6 [11.2] mm Hg vs 14.1 [14.2] mm Hg; P = .05). This blunted acute hyperemic response correlated with final infarct size (ρ, -0.29; P = .02). The resistive reserve ratio was lower at the acute moment vs follow-up (mean [SD], 3.4 [1.7] vs 5.0 [2.7]; P < .001). CONCLUSIONS AND RELEVANCEIn the acute setting of STEMI, nonculprit coronary flow reserve was reduced and FFR was augmented, whereas instantaneous wave-free ratio was not altered. These results may be explained by an increased hyperemic microvascular resistance and a blunted adenosine responsiveness at the acute moment that was associated with infarct size.

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Aims To evaluate the prognostic value of global and regional quantitative [15O]H2O positron emission tomography (PET) perfusion. Methods and results In this retrospective study, 648 patients with suspected or known coronary artery disease (CAD) who underwent [15O]H2O PET were followed for the occurrence of death and myocardial infarction (MI). Global and regional hyperaemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) were obtained from [15O]H2O PET. During median follow-up of 6.9 (5.0–7.9) years, 64 (9.9%) patients experienced the composite of death (36–5.6%) and MI (28–4.3%). Impaired global hMBF (&lt;2.65 mL/min/g) and CFR (&lt;2.88) were both significant prognostic factors for death/MI after adjusting for clinical characteristics (both P &lt; 0.001). However, after adjusting for clinical parameters and the combined use of hMBF and CFR, only hMBF remained an independent prognostic factor (P = 0.04). For regional perfusion, both impaired hMBF (&lt;2.10 mL/min/g) and CFR (&lt;2.07) demonstrated prognostic value for events (both P &lt; 0.001). Similarly, after adjusting for clinical characteristics and combined use of hMBF and CFR, only hMBF had independent prognostic value (P = 0.04). The combination of global and regional perfusion did not improve prognostic performance over either global (P = 0.55) or regional perfusion (P = 0.37) alone. Conclusion Global and regional hMBF and CFR were all prognostic factors for death and MI. However, for both global and regional perfusion, hMBF remained the only independent prognostic factor after adjusting for the combined use of hMBF and CFR. Additionally, integrating global and regional perfusion did not increase prognostic performance compared to either regional or global perfusion alone.

Aims Continuous thermodilution is a novel technique to quantify absolute coronary flow and microvascular resistance (MVR). Notably, intracoronary infusion of saline elicits maximal hyperaemia, obviating the need for adenosine. The primary aim of this study was to validate continuous thermodilution in humans by comparing invasive measurements to [15O]H2O positron emission tomography (PET). As a secondary goal, absolute flow and MVR were compared between invasive measurements obtained with and without adenosine. Methods and results Twenty-five patients underwent coronary computed tomography angiography (CCTA), [15O]H2O PET, and invasive assessment. Absolute coronary flow and MVR were measured in the left anterior descending and left circumflex artery using a dedicated infusion catheter and a temperature/pressure sensor-tipped guidewire. Invasive measurements were performed with and without adenosine. In order to compare invasive flow measurements with PET perfusion, subtending myocardial mass of the investigated vessels was derived from CCTA using the Voronoi algorithm. Invasive and non-invasive measurements of adenosine-induced hyperaemic flow and MVR showed strong correlation (r = 0.91; P < 0.001 for flow and r = 0.85; P < 0.001 for MVR) and good agreement [intraclass correlation coefficient (ICC) = 0.90; P < 0.001 for flow and ICC = 0.79; P < 0.001 for MVR]. Absolute flow and MVR also correlated well between measurements with and without adenosine (r = 0.97; P < 0.001 for flow and r = 0.98; P < 0.001 for MVR) and showed good agreement (ICC = 0.96; P < 0.001 for flow and ICC = 0.98; P < 0.001 for MVR). Conclusions Continuous thermodilution is an accurate method to measure absolute coronary flow and MVR, which is evidenced by strong agreement with [15O]H2O PET derived flow and resistance. Absolute flow and MVR correlate highly between invasive measurements obtained with and without adenosine, which confirms that intracoronary infusion of room temperature saline elicits steady-state maximal hyperaemia.

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Background: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention (pPCI), coronary microvascular injury (MVI) occurs in a large proportion of STEMI patients, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated if ticagrelor maintenance therapy after revascularized STEMI is associated with less MVI compared to prasugrel maintenance therapy. Methods: A total of 110 STEMI patients received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after pPCI. The primary outcome was MVI at 1 month, as determined with the index of microcirculatory resistance (IMR) in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at one month. Results: The primary outcome of IMR was not superior in ticagrelor or prasugrel treated patients (ticagrelor 21 [15-39] U, prasugrel 18 [11-29] U, p=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor-13.9 U vs. prasugrel-13.5 U, p=0.54). Intramyocardial hemorrhage was observed less frequently in patients with ticagrelor (23% vs. 43%, p=0.04). At one month no difference in infarct size was observed (ticagrelor 7.6 [IQR 3.7-14.4] g, prasugrel 9.9 [IQR 5.7-16.6] g, p=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%, p=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. Conclusions: In patients with STEMI, ticagrelor maintenance therapy was not superior to prasugrel in preventing MVI in the infarct-related territory as assessed by IMR and this resulted in a comparable infarct size at one month.

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