Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia: The Randomized RAIN-FLOW Study

Abstract

Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.

Keywords: ST‐segment‐elevation myocardial infarction; absolute coronary blood flow; hyperemia; no reflow phenomenon; primary percutaneous coronary intervention.

Figure 1. Study interventions (as per protocol).

ADE indicates adenosine; MMR, minimal microcirculatory resistance; NTP, nitroprusside; PPCI, primary percutaneous coronary intervention; and STEMI, ST‐segment–elevation myocardial infarction.

Figure 2. Study flow chart.

*Successful PPCI was defined as final TIMI 3 flow. ^†Patients with unsuccessful PPCI not suitable for the study were mostly subacute myocardial infarction, end‐stage renal dysfunction, distal thrombus embolization during PPCI, patients resuscitated from out‐of‐hospital cardiac arrest, and cardiogenic shock. Those patients were not registered in the screening failure list. ^‡Other causes of screening failure included urgency to end the procedure for laboratory demand (n=4), technical issues with the infusion pump (n=2), patient refused to participate (n=2), and included in other clinical trial (n=1). ^§One patient of the flow‐mediated hyperemia group presented with coronary dissection during the advance of pressure wire and required a stent implantation. This patient completed the study protocol after treatment of the coronary dissection. PPCI indicates primary percutaneous coronary intervention; STEMI, ST‐segment–elevation myocardial infarction; and TIMI, Thrombolysis in Myocardial Infarction.

Figure 3. Primary end points.

Boxplot of the study end points before and after treatment. Of note, MMR was not assessed before treatment in the pharmacologic group. In this group, MMR was assessed after administration of hyperemic drugs. In the flow‐mediated hyperemia group, MMR values were assessed during saline infusion at 15 (before treatment) and at 135 seconds (after treatment). MMR indicates minimal microcirculatory resistance; and TIMI, Thrombolysis in Myocardial Infarction.

Figure 4. Saline‐induced thermodilution patterns in patients with slow‐flow.

*Start of saline infusion; ^†Saline temperature. Appropriate saline clearance is shown in images (A through F). Acute RCA occlusion (A). Restoration of TIMI 2 flow after thrombus aspiration (B) with no improvement after stent implantation (C). Flow‐mediated hyperemia (D). The thermodilution‐based ACBF and MMR (F) showed similar values at 15 seconds (145 mL/min and 450 Wood units) and at 135 seconds (129 mL/min and 513 Wood units) without variation of the distal temperature (from −0.35 to −0.39°). However, normal TIMI 3 flow restoration was observed after flow‐mediated hyperemia (E). Deficient saline clearance is shown in images (G through L). Acute LAD artery occlusion (G). Restoration of TIMI 3 flow after thrombus aspiration (H) followed by no reflow (TIMI flow 1) after stent implantation (I). Flow‐mediated hyperemia (J). The thermodilution‐based ACBF and MMR (L) showed significant changes from 15 seconds (83 mL/min and 763 Wood units) to 135 seconds (54 mL/min and 1184 Wood units) due to progressive decrease of distal temperature (from −0.96 to −1.47°) during saline infusion (J). TIMI 2 flow was observed posttreatment (K). ACBF indicates absolute coronary blood flow; LAD, left anterior descending; MMR, minimal microcirculatory resistance; RCA, right coronary artery; and TIMI, Thrombolysis in Myocardial Infarction.

Figure 5. Absolute coronary blood flow and minimal microcirculatory resistance changes between baseline and follow‐up procedures.

Fourteen patients underwent thermodilution‐based physiologic assessment at baseline (post intervention) and at follow‐up. Baseline values were estimated at 15 seconds in the pharmacologic (blue) and at 135 seconds in the flow‐mediated hyperemia group (red).