Distal administration of very high doses of intracoronary adenosine for the treatment of resistant no-reflow

Abstract

No-reflow is a serious condition, and is associated with substantial morbidity and mortality after percutaneous coronary intervention. The most feared complication of no-reflow is a case of no-reflow that is resistant to multiple drug therapy. This condition usually occurs in patients with distal coronary disease or high thrombus burden. In the present case, a patient with resistant no-reflow that could be reversed by distal intracoronary administration of very high doses of adenosine (1 mg) is described. Administration of very high doses of adenosine via a balloon catheter was safe and did not cause any changes in the heart rate or blood pressure. The present case is the first to be reported in the literature.

CASE PRESENTATION

A 69-year-old man presented with sudden, witnessed cardiac arrest. He was found to have inferior myocardial infarction with 5 mm ST elevation in inferior leads. The patient was transferred to the University of Arizona Medical Center, Arizona, USA, for emergent intervention. Cardiac catheterization revealed severe diffuse distal left anterior descending and circumflex coronary artery disease, in addition to a 100% occluded proximal right coronary artery (RCA) (Figure 1). A balanced middle weight wire (Guidant Corporation, USA) was used to cross the lesion without any difficulties. The patient was initially treated with heparin and double-bolus eptifibatide. A 2.5 mm × 18 mm Maverick balloon catheter (Boston Scientific, USA) was initially used for predilation with establishment of distal Thrombolysis in Myocardial Infarction (TIMI) 2 flow (Figure 2). Next, a 3.5 mm × 23 mm Taxus stent (Boston Scientific, USA) was deployed at 16 atm. Poststenting, the patient developed no-reflow in the RCA (Figure 3). Multiple intracoronary doses of 60 μg of adenosine, 100 μg of nitroprusside and 100 μg of nitroglycerin failed to resolve the no-reflow, and the patient still had TIMI 2 flow with reduced myocardial blush. As expected, bradycardia was temporarily present during each adenosine injection. The presence of thrombus in the distal RCA was also noted. Therefore, one-tenth of the bolus dose of eptifibatide mixed with 20 mL of the patient’s blood was given via an intracoronary route, but without success. Because of the presence of distal thrombus (Figure 4), a pacemaker was inserted and Anjiojet rheolytic thrombectomy (Possis Medical, USA) was attempted with no improvement in the flow. Next, an over-the-wire 2.0 mm × 15 mm Maverick balloon was advanced into the distal RCA, and two 1000 μg doses of adenosine were administered through this balloon. The patient tolerated the injections well, with no effect on the blood pressure or heart rate during or after administration of very high doses of adenosine. However, distal flow improved significantly with improved myocardial blush, and there was a marked improvement in the ST-segment elevation in the inferior leads (Figure 5).

Figure 1.

Occluded right coronary artery

Figure 2.

Right coronary artery visualized after balloon angioplasty

Figure 3.

No-reflow after stenting of proximal right coronary artery

Figure 4.

Suspected distal thrombus formation

Figure 5.

Resolution of no-reflow after administration of two very high doses of adenosine (1000 μg) into the distal right coronary artery via a balloon catheter

DISCUSSION

The prevalence of no-reflow occurs in 0.6% to 5% of percutaneous coronary interventions (1,2), with high incidence in patients undergoing percutaneous coronary intervention for acute myocardial infarction, vein graft interventions and rotational atherectomy (3). It can be as high as 50% in coronary arteries with high thrombus burden (4). No-reflow is usually related to platelet aggregation, distal embolization, spasm of microcirculation (1,5), tissue edema (6) or a combination of many factors. The occurrence of no-reflow has been associated with adverse outcomes, which can be as high as 10 times that of a historical control (1,7–10). Patients with reversible no-reflow have been associated with lower 30-day mortality than patients with adequate reflow (11). Therefore, once no-reflow occurs, every attempt must be made for rapid restoration of TIMI 3 flow and myocardial blush. The focus of treatment has been on the use of vasodilators. The three most commonly used vasodilators in this setting are verapamil, nitroprusside and adenosine. Intracoronary administration of verapamil has been shown to improve flow in patients with no-reflow (1,12,13). However, in a small, nonrandomized trial (14), verapamil has failed to reduce the death rate or myocardial infarction. Intracoronary nitroprusside has also been successfully used in this clinical setting (12,15), but it too has failed to show any reduction in mortality (14). Adenosine is a potent vasodilator of distal vessels and has been shown to restore flow in a dose-dependent manner (12,16,17), with reduction in adverse outcome and death in small trials (17).

Despite aggressive treatment with multiple drugs, no-reflow can be resistant to many treatments, resulting in higher adverse outcomes (11). New therapeutic modalities, such as intracoronary adrenaline, intracoronary thrombolysis or combinations of different drugs, have been partially successful in the treatment of resistant no-reflow (18–24).

The distal injection of vasoactive medications has the advantage of allowing a high concentration of the drug near the distal coronary bed, with lower incidence of side effects. Additionally, there may be a theoretical benefit of direct mechanical breakage of thrombus material by rapid bolus injection via a small lumen catheter. Successful treatment of resistant no-reflow has been reported by distal injection of verapamil in high doses directly into the distal coronary vessel through a perfusion catheter (24,25). However, verapamil has a long half-life, and systemic effects could limit the use of this medication in higher doses. However, adenosine has the distinct advantage of a very short half-life compared with other drugs and, therefore, adverse effects are rapidly self-limiting. Refractory no-reflow has been successfully treated using distal injection of multiple doses of adenosine (24). However, administration of very high doses of adenosine in the distal coronary bed has not been reported previously. In the present case report, we documented the safety and efficacy of injecting very high doses of adenosine (up to 1 mg) into the distal RCA, with no effect on the heart rate or blood pressure. We believe that by placing the catheter beyond the branch leading to the atrioventricular node, the risk of bradycardia was greatly reduced. Because of the very short half-life of adenosine, the drug was completely eliminated before the second-pass. Based on our experience, distal injection of very high doses of adenosine (up to 1 mg) appears to be safe and can be attempted in refractory no-reflow cases. In particular, this approach is very attractive in patients with severe hypotension, bradycardia or cardiogenic shock.