Case presentation

A 37-year-old woman with multiple atherosclerotic risk factors was in her usual state of health until approximately 1:00 pm on the day of admission, when she developed the acute onset of substernal chest pain. She presented to the emergency department approximately 4½ hours later. The initial electrocardiogram revealed anterior ST-segment elevation. She was promptly treated with aspirin, clopidogrel, unfractionated heparin, sublingual nitroglycerin, morphine sulfate, and metoprolol, and was referred promptly to the cardiac catheterization laboratory.

Significant past medical history included lupus nephritis with stage 4 chronic kidney disease and proteinuria, hypertension, obesity, type 2 diabetes mellitus (poorly controlled), and dyslipidemia. She had never smoked, and denied use of alcohol or illicit drugs. Her medications on admission included glipizide, pioglitazone, atenolol, amlodipine, sodium bicarbonate, hydrochlorothiazide, omeprazole, and candesartan. On admission, her blood pressure was 159/91 mmHg, her heart rate was 86 bpm, and the rest of her physical exam was unremarkable. Admission laboratory values were notable for hyperglycemia (glucose 325 mg/dL), and renal insufficiency (serum creatinine 2.2 mg/dL).

Cardiac catheterization

The initial coronary angiogram showed occlusion of the left anterior descending (LAD) coronary artery with the appearance of intraluminal thrombus (Figure 43-1 and Video 43-1). The circumflex and right coronary arteries were without significant obstruction. The operator decided to proceed with immediate PCI of the LAD. The ACT was adjusted with additional boluses of unfractionated heparin to maintain an ACT between 250 and 300 seconds, and eptifibatide was administered as adjunctive therapy (two intravenous boluses, each of 180 mcg/kg, and an infusion of 2.0 mcg/kg per minute continued for 14 hours). The left coronary artery was engaged with a JL4 guide, and the lesion was easily crossed with a 0.014 inch floppy-tipped guidewire. In this case, a thrombus extraction catheter was not used. The operator centered a 2.5 mm diameter by 15 mm long compliant balloon on the lesion and inflated it to 6 atmospheres of pressure (Figure 43-2). Following balloon angioplasty, there was a good angiographic result with resolution of the stenosis and thrombus, but “slow reflow” was noted in the LAD, with significantly slower filling of the distal LAD compared with the circumflex artery (Figure 43-3 and Video 43-2). To treat the slow flow, the operator administered boluses of intracoronary adenosine via the guiding catheter, beginning with boluses of 50 mcg and increasing to 80 mcg as tolerated. Flow improved, although it remained abnormal. At this point, the operator treated the lesion with a 3.0 mm diameter by 18 mm long paclitaxel-eluting stent and further dilated it with 16 atmospheres inflation pressure using a 3.5 mm diameter by 15 mm long noncompliant balloon. Flow worsened after stenting (Figures 43-4, 43-5 and Videos 43-3, 43-4). Again, the operator administered multiple intracoronary boluses of adenosine via the guiding catheter, beginning with boluses of 50 mcg and increasing to 80 mcg as tolerated, until a total of 700 mcg had been administered. At the conclusion of the case, LAD flow was improved, although it had not returned to normal. The patient reported resolution of chest pain and remained hemodynamically stable, although persistent ST elevation was noted on the monitor and on a subsequent 12-lead ECG. The right femoral access sheath was removed with manual compression after 4 hours when the ACT measured less than 180 seconds but while the eptifibatide infusion was continuing.

FIGURE 43-1 This left coronary angiogram in the right anterior oblique cranial view shows acute occlusion of the mid-left anterior descending coronary artery. Intraluminal thrombus is seen as a persistent space-filling defect with contrast surrounding the thrombus on three sides. This is a typical appearance of an acutely occluded coronary artery.

FIGURE 43-2 This left anterior oblique cranial view shows an inflated angioplasty balloon in the midportion of the left anterior descending coronary artery.

FIGURE 43-3 This left anterior oblique cranial view following balloon angioplasty shows patency of the left anterior descending coronary artery. The video images show slow distal coronary blood flow despite multiple doses of intracoronary adenosine.

FIGURE 43-4 This left anterior oblique cranial view following coronary stenting using a long paclitaxel drug-eluting stent shows patency of the left anterior descending coronary artery. The video images show slow distal coronary blood flow despite multiple doses of intracoronary adenosine.

FIGURE 43-5 This right anterior oblique cranial view following coronary stenting using a long paclitaxel drug-eluting stent shows patency of the left anterior descending coronary artery. The video images show slow distal coronary blood flow despite multiple doses of intracoronary adenosine.

Postprocedural course

Following the catheterization, she was admitted to the coronary care unit. A 12-lead ECG demonstrated persistent ST-segment elevation. She remained hemodynamically stable and free of symptoms. Because of her renal insufficiency and exposure to contrast, she was treated with N-acetylcysteine. Over the next 48 hours, her renal function deteriorated, with the serum creatinine peaking at 3.1 mg/dL before returning to baseline in 5 days. An echocardiogram showed anterior hypokinesis and apical akinesis with an ejection fraction of 35% to 40%. She was discharged on aspirin, clopidogrel, atorvastatin, niacin, carvedilol, and candesartan along with her diabetic medications.

She had no further cardiac symptoms during follow-up. Two years later, she developed end-stage renal failure from lupus nephropathy and required long-term dialysis. After the onset of end-stage renal failure, she began to report shortness of breath, and her left ventricular function appeared worse, with an estimated ejection fraction of 25%. Repeat cardiac catheterization showed total occlusion of the LAD at the site of the previous drug-eluting stent and severe left ventricular dysfunction (Figures 43-6, 43-7 and Videos 43-5, 43-6). She was treated with an implantable defibrillator for primary prevention of ventricular arrhythmias and her medications for congestive heart failure were optimized.

FIGURE 43-6 This right anterior oblique cranial left ventriculogram was taken 2 years later when the patient re-presented with congestive heart failure. There is severe anterior and apical akinesis with a filling defect in the left ventricular apex consistent with left ventricular apical thrombus.

FIGURE 43-7 This left coronary angiogram in the right anterior oblique cranial view shows chronic reocclusion of the mid-left anterior descending coronary artery 2 years later at the site of the previous stent.

Discussion

The terms “no-reflow” or “slow-reflow” describe the phenomenon when there is an apparent reduction in coronary blood flow seen by angiography following a percutaneous coronary revascularization procedure, despite the presence of a widely patent lumen and in the absence of a mechanical complication such as a dissection.¹ As seen in this case, no-reflow can initially occur immediately after balloon angioplasty but is often exacerbated by stenting, presumably due at least in part to distal embolization of atherothrombotic material during stent expansion (“cheese-grater effect”). No-reflow can occur in up to 5% of PCI procedures and is more commonly seen with acute coronary syndromes, during rotational atherectomy, and in saphenous vein bypass graft interventions. In the last, distal protection devices can significantly reduce the frequency of no-reflow. No-reflow is more commonly seen during acute PCI for acute ST-elevation MI as in this case.^2,3 Other predictors of the no-reflow phenomenon include the presence of bulky and large plaque burden, intracoronary thrombus, lipid pools (seen on intravascular ultrasound), and total coronary occlusion on the presenting angiogram. In a study comparing coronary aspirates from patients with normal flow to those with no-reflow, the latter contained more atheromatous plaque, more platelets and thrombotic material, more macrophages, and more cholesterol crystals.⁴

In addition to distal embolization, presumed mechanisms of the no-reflow phenomenon include myocardial necrosis, reperfusion injury, macrovascular and microvascular vasoconstriction, local increase in angiotension II receptor density, and neutrophil activation with plugging and endothelial interaction. Diminished microvascular flow can be determined clinically in a qualitative manner by observing slower filling of the infarct artery compared to the opposite artery. Semiquantitative methods include TIMI frame count, TIMI blush score, contrast echocardiography, intracoronary Doppler measurement, and advanced imaging techniques using MRI.

The no-reflow phenomenon is a clinically important finding, as it is associated with significantly worse outcomes. No-reflow is associated with increased mortality, which reaches as high as 27% in some series. It is associated with greater microvascular damage, persistent elevation of the ST segments by ECG, and worse left ventricular function. Patients with no-reflow phenomenon and poor left ventricular function with microvascular damage are at increased risk for late stent closure, as was observed in this case.

Once it develops, no-reflow has been treated in the cardiac catheterization laboratory with mixed success, using intracoronary adenosine, nitroprusside, or verapamil. Other medications have also been reported as effective including abciximab and eptifibatide; however, none of these agents have been well-studied in a randomized, controlled fashion and definitive proof regarding their efficacy is lacking. In addition, none of these agents is specifically approved for this indication. While most operators administer these drugs through the guide catheter, some operators have proposed selective delivery directly into the distal coronary bed using subselective catheters positioned distally in the coronary artery. This approach has, anecdotally, been found effective when injection into the guide showed no improvement in flow.

The initial approach to primary PCI reperfusion for acute ST-elevation myocardial infarction has been an evolving field. Based on recent randomized controlled trials, there is increasingly compelling data to suggest that routine performance of thrombus extraction with a simple aspiration catheter improves clinical outcomes prior to stenting for acute ST-elevation MI.^4,5 The procedure in the case presented here was performed prior to the routine use of these devices and this may have contributed to the no-reflow that complicated her intervention.