Case presentation

An active and healthy 66-year-old man with no prior cardiac history developed acute onset of midsternal chest pain radiating to his back and left shoulder, associated with nausea. He presented to the emergency department after experiencing symptoms for 45 minutes and rapidly became pain-free following administration of nitroglycerin. His medical history is notable for hypertension, dyslipidemia, a family history of premature coronary disease, and remote tobacco use. His medications on presentation included metoprolol, amlodipine, hydrochlorothiazide, and atorvastatin. Physical exam found no important abnormalities, and the initial electrocardiogram obtained without pain showed nonspecific ST-T wave changes. Serial troponins peaked at 1.7 ng/dL; the remaining routine laboratory studies were normal.

Cardiac catheterization

Diagnosed with a non-ST segment elevation acute myocardial infarction, he was admitted to a telemetry unit and treated with aspirin, enoxaparin, nitroglycerin, atorvastatin and metoprolol. He remained pain-free and underwent cardiac catheterization the following day. Left ventriculography was normal. Coronary angiography noted nonobstructive luminal irregularities in the right coronary and left circumflex arteries and severe narrowing in the proximal segment of the left anterior descending artery (Figure 20-1). Compared to the circumflex artery, angiographic flow appeared reduced at baseline (Video 20-1). After the intravenous administration of unfractionated heparin and eptifibatide, balloon angioplasty was performed using a 2.5 mm diameter by 20 mm long compliant balloon. Angiography performed after balloon dilatation showed complete occlusion of the left anterior descending artery at the site of the intervention (Video 20-2). The patient developed chest pressure but remained hemodynamically stable. An intracoronary bolus dose of 100 mcg of adenosine delivered through the guide catheter improved flow slightly; however, the entire artery did not fill with contrast (Video 20-3). There did not appear to be a dissection or other luminal problem responsible for the reduced flow, and the activated clotting time (ACT) was 280 seconds. The operator then deployed a tacrolimus-eluting stent (3.0 mm diameter by 28 mm long). Flow remained reduced, and the patient continued to experience chest pain after stenting despite repeated bolus injections of 100 mcg of adenosine (total of 500 mcg) injected through the guide catheter (Figure 20-2 and Video 20-4). At this point, the operator positioned an infusion catheter (Rapid Transit™ Catheter, Cordis Corporation) in the distal left anterior descending artery and injected an additional 100 μg adenosine. Subsequent angiography demonstrated nearly normal flow (Video 20-5) and the patient’s chest discomfort resolved.

FIGURE 20-1 Coronary angiography performed in a right anterior oblique projection with cranial angulation, showing a severe stenosis in the proximal left anterior descending artery (arrow).

FIGURE 20-2 This angiogram of the left coronary artery in a right anterior oblique projection with cranial angulation was obtained after stent placement and shows no flow past the stent. The site of the previous stenosis shows no residual luminal narrowing and there does not appear to be a dissection.

Postprocedural course

Following the procedure, the patient had no further symptoms and was discharged the next morning on aspirin, clopidogrel, atorvastatin, metoprolol, lisinopril, and hydrochlorothiazide. He continued to remain active and reported no symptoms 6 months later.

Discussion

The angiographic appearance of markedly reduced coronary flow in the absence of luminal obstruction is termed the “no-reflow” phenomenon. No reflow implies patency of the epicardial artery but inadequate tissue perfusion. Two distinct clinical entities are associated with the no-reflow phenomenon: 1) following reperfusion therapy for acute myocardial infarction, and 2) as a complication of a coronary intervention.

Although related, the dominant mechanism responsible for no reflow in these two settings differ.^1,2 The no-reflow observed after reperfusion for an acute myocardial infarction is likely a consequence of ischemic microvascular dysfunction, myocardial edema, inflammation, and reperfusion injury; there also may be a component of distal embolization due to thrombus or necrotic plaque. No-reflow observed as a complication of percutaneous coronary intervention is usually due to microvascular obstruction from embolization of plaque components, platelets, and thrombi.

Coronary dissection, vasospasm, and air embolism may masquerade as no–reflow, and these conditions should be carefully excluded. Although the no-reflow phenomenon complicates less than 5% of all coronary interventions, there is a higher frequency of no-reflow following interventions associated with distal embolization, including saphenous vein graft lesions, atheroablative procedures such as rotational atherectomy, and coronary intervention performed in the setting of acute coronary syndromes. In addition, several plaque characteristics are associated with an increased risk of no-reflow (Table 20-1).^1,2

TABLE 20-1 Characteristics Associated with No-Reflow After Coronary Intervention

The case presented here is typical for no-reflow complicating a coronary intervention. The angiographic appearance is classic and is characterized by slow penetration of a widely patent artery with failure to rapidly and completely fill the artery. The patient presented with an acute coronary syndrome and the culprit lesion appeared irregular and long with diminished flow at baseline. Another important feature exemplified by this case is the fact that flow appeared to worsen with each additional coronary manipulation. This behavior is typical and the operator should always be wary of performing ancillary inflations during an intervention complicated by no-reflow. This is true even if flow is restored, since additional manipulations may cause further deteriorations in flow that may not reverse. In the case presented here, the no-reflow was, fortunately, well-tolerated and reversed by the completion of the case, resulting only in prolonged chest pain. Prolonged and sustained no-reflow may lead to serious sequelae such as hemodynamic collapse, arrhythmia, periprocedural myocardial infarction, and death.

Among pharmacologic agents successful at restoring or improving flow, intracoronary administration of nitroprusside (200 mcg), adenosine (24 to 1000 mcg), and verapamil (50 to 900 mcg) are most popular.^3–5 Intracoronary nitroglycerin is not effective, primarily because of its lack of effect on the resistance arterioles. The platelet glycoprotein IIb/IIIa receptor antagonists have a role in preventing this complication in the setting of acute coronary syndrome, and distal protection devices reduce the no-reflow phenomenon in the case of saphenous vein graft interventions.

In the case presented here, intracoronary administration of high doses of adenosine failed to improve flow. This was likely due to the profound flow reduction present and the inability of the drug to reach the target site (the microcirculation vessels) by intracoronary injection. Adenosine became effective only when the drug was delivered directly into the distal arterial bed by injection through the transit catheter.