CORONARY angiography is considered to be the clinical gold standard for the characterization of coronary artery atherosclerosis. We describe a case of a patient with a history of angina whose coronary angiogram identified only minimal lesions. Six months later, the patient had a cardiac arrest during induction of anesthesia. Postmortem evaluation revealed severe (70–90%) stenoses of all three major coronary arteries. The failure of the preoperative angiogram to detect the severity of this patient's disease is discussed.

A 47-yr-old, 61-kg man was scheduled to undergo revision of a left femoral to popliteal bypass graft. In addition to his chief complaint of claudication, the patient had chest pain typical of angina. He had several risk factors for coronary artery disease, including hypertension, hyperlipidemia, a 20 pack-year smoking history, and a positive family history. Serial electrocardiograms had shown no specific ischemic changes. Cardiac enzymes, measured during a recent hospital admission for angina, were normal.

An exercise stress echocardiogram was nondiagnostic, secondary to the patient's decreased ability to exercise. His ejection fraction was estimated to be 50%. No other test of functional capacity was performed. In September 2000, he underwent a left heart catheterization and coronary angiography. The angiogram showed diffuse luminal irregularities in both the left and right coronary arteries; however, the maximal lesion was interpreted as a 40% stenosis of the right coronary artery (figs. 1A–C).

Fig. 1. Coronary angiograms showing a 40% stenosis of the right coronary artery (A ), and two views of the left anterior descending coronary artery and the left circumflex coronary artery demonstrating only diffuse luminal irregularities (B  and C ).

Fig. 1. Coronary angiograms showing a 40% stenosis of the right coronary artery (A ), and two views of the left anterior descending coronary artery and the left circumflex coronary artery demonstrating only diffuse luminal irregularities (B  and C ).

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The patient's daily medications included isosorbide (10 mg three times daily), metoprolol (25 mg twice daily), aspirin (325 mg daily), and sublingual nitroglycerin (as needed). He underwent uneventful general anesthesia in October 2000 for a left femoral–popliteal bypass. This attempt at revascularization was unsuccessful, and the patient was scheduled for a revision.

In January 2001, cardiologists again noted that the recent angiogram (obtained in September 2000) had shown noncritical disease of the right coronary artery, with maximal stenosis of 40%. The patient was characterized as being “low risk” for surgery. Vasospasm and esophageal spasm were mentioned as possible etiologies for the stable chest pain. Close perioperative monitoring and treatment with nitroglycerin were recommended. Diltiazem, instead of metoprolol, was prescribed; however, the patient did not implement this change.

The patient presented for surgery in March 2001. Preoperatively, his blood pressure was 166/87 mmHg, with a pulse of 80 beats/min. That morning, he had taken metoprolol, isosorbide, and aspirin. As premedication, he received midazolam (2 mg) intravenously. Routine monitors were applied. After preoxygenation, anesthesia was induced with sodium thiopental (375 mg), lidocaine (60 mg), and fentanyl (100 μg). Succinylcholine (100 mg) was used to facilitate tracheal intubation. The first blood pressure after intubation was 176/105 mmHg, with a pulse of 101 beats/min. Isoflurane (1%) and esmolol (22 mg) were administered. Minutes later, the anesthesiologist was unable to obtain a blood pressure. The patient had no palpable pulse, although the electrocardiogram showed a rate of 95 beats/min. This rhythm quickly deteriorated to a wide-complex tachycardia and then either ventricular fibrillation or asystole. Isoflurane was discontinued, and cardiopulmonary resuscitation was initiated. Defibrillation was attempted three times in rapid succession with 360 J. Ventilation continued with 100% oxygen. Epinephrine, lidocaine, magnesium, hydrocortisone, amiodarone, atropine, glucagon, and calcium chloride were administered. Arterial and central venous cannulation were established during the resuscitation. Initial arterial blood gas measurements were pH, 7.44; arterial carbon dioxide tension (Paco2), 14 mmHg; and arterial oxygen tension (Pao2), 544 mmHg, with a serum potassium of 3.7 mEq/l. Additional attempts at defibrillation were made. A chest radiograph showed no pneumothorax. After approximately 40 min of chest compressions, the electrocardiogram showed a wide-complex rhythm followed by sinus tachycardia, with a systolic blood pressure greater than 200 mmHg. The patient was transported to the intensive care unit on lidocaine, nitroglycerin, and epinephrine infusions.

Later that day, the patient suffered two additional episodes of ventricular fibrillation, which were terminated with electrical defibrillation. Cardiac enzymes, electrocardiography, and echocardiography were all consistent with an anteroseptal myocardial infarction. The next morning, he was awake and able to follow verbal commands. Two days after the initial cardiac arrest, he developed a ventricular tachycardia, which evolved into ventricular fibrillation. Resuscitation was attempted for 30 min without success.

An autopsy showed the left ventricle of the heart to be mildly hypertrophied. The myocardium of the anterior portion of the left ventricle was acutely infarcted. There was also a small, well-healed scar in the anterior left ventricular wall. The coronary arteries had severe concentric atherosclerotic plaques throughout their lengths. There was 90% luminal narrowing of the left anterior descending coronary artery, 80% of the left circumflex artery, and 70% of the right coronary artery at 1.5 cm, 1.8 cm, and 1.5 cm, respectively, from the arterial origins (figs. 2A–C). There was no evidence of hemorrhage, thrombosis, or rupture within the plaques.

Fig. 2. Postmortem histologic images of the left anterior descending coronary artery (A ), the left circumflex artery (B ), and the right coronary artery (C ), all depicting severe concentric atherosclerosis (estimated to be 70– 90%).

Fig. 2. Postmortem histologic images of the left anterior descending coronary artery (A ), the left circumflex artery (B ), and the right coronary artery (C ), all depicting severe concentric atherosclerosis (estimated to be 70– 90%).

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Coronary artery angiography is considered the definitive study in the evaluation of coronary atherosclerosis, impacting medical and surgical management. Our patient had physical symptoms strongly suggestive of myocardial ischemia and multiple risk factors for coronary artery disease. However, an angiogram performed 6 months prior to planned surgery falsely reassured clinicians involved in his perioperative care about the extent of coronary atherosclerosis. The maximal lesion noted by angiography was 40% stenosis in the right coronary artery, with mild irregularity of the left coronary artery. Postmortem examination, surprisingly, revealed severe diffuse three-vessel disease.

The limitations of coronary artery angiography have been discussed in the cardiology literature. 1–3The percentage of stenosis is calculated by comparing the lumen of the stenotic area to that of an adjacent, presumably healthy, arterial segment. Coronary intravascular ultrasound, which depicts cross-sectional tomographic views of the vascular wall and lumen, has shown that only 6.8% of 884 angiographically normal reference segments were actually normal. 4Therefore, in patients with diffuse disease, angiographers often compare severely atherosclerotic areas to less diseased ones. This contributes to underestimation of the actual stenosis. Diffuse, concentric, and symmetric involvement of the vessel may also present the illusion of a smaller artery, without focal constriction, in the two-dimensional angiogram. 1,3 

There are other conditions that may confound the angiographic impression. The Glagov phenomenon is compensatory dilatation of atherosclerotic arterial wall, which is thought to be due to rearrangement of medial smooth muscle cells. 5,6This arterial remodeling increases the cross-sectional area and prevents functional narrowing until 40–50% of the cross-section is occupied by plaque. Despite the presence of mild to moderate disease, the lumen will appear almost normal on angiography. 5,7Further plaque enlargement will decrease the arterial lumen.

Numerous other factors associated with unreliable angiographic data include complexity of lesions (eccentric or slit-like lesions are troublesome), distension of vessels at systemic pressures, dye distension, intraobserver or interobserver variability, overlapping of branches, foreshortening, disease at bifurcations, flush occlusions, inadequate dye filling, vasospasm (overestimates), blurring due to motion during the cardiac cycle, and resolution of angiographic equipment. 1–3,8Lesions in the left main coronary artery are especially difficult to detect. 9Coronary angiography is even less reliable after mechanical intervention associated with angioplasty or stent deployment. 1,2Quantitative computerized angiography has most of the same shortcomings. 1,10The two-dimensional nature of conventional angiography contributes to many of these problems. Physiologic coronary flow reserve, as measured by reactive hyperemia, does not correlate with measurement of percent stenosis on angiography. 11This may be partially explained by underestimated stenosis.

At least 11 studies have described discrepancies between premortem angiographic and postmortem histologic estimations (performed 1 day to 3 yr apart) of the severity of coronary artery disease. 9,12–22Angiography generally underestimates lesion severity. Conversely, postmortem pathology tends to overestimate it. Pathologists assess the percentage of stenosis by dividing luminal area by the total area occupied by plaque. 6,8When arterial remodeling occurs, the cross-sectional area occupied by the plaque may initially increase, without luminal encroachment. This may lead to overestimation of the percentage of arterial stenosis, compared to the actual decrease in the luminal area. Other factors, such as lack of systemic distending pressure, postmortem arterial shrinkage, and changes with fixation, may lead to errors. If there has been a sufficiently long interval of time between the two studies, the lesion could have truly progressed. Generally, however, histologic estimates of stenoses are reliable for lesions over 75% in diameter. 6 

In our patient, diffuse concentric atherosclerotic disease had narrowed the entire length of all three coronary arteries. We believe that the degree of stenosis was angiographically underassessed due to the lack of a normal reference segment. The patient presumably had similar coronary artery lesions during his previous surgery. A review of his records revealed that his heart rate was better controlled during the previous anesthetic induction (a resting pulse of 50–60 beats/min, with no increase during induction and laryngoscopy). When he presented for the surgical procedure discussed in this case report, his pulse was 80 beats/min, and it increased to 101 beats/min following tracheal intubation. There were no other significant differences between the conduct of the two anesthetic inductions. It is possible that given his severe degree of coronary vascular compromise, this patient was unable to tolerate even a mild elevation in heart rate.

Since the patient underwent prolonged cardiopulmonary resuscitation, he was not considered a candidate for thrombolytic therapy. He may have benefited from urgent percutaneous transluminal coronary angioplasty. Although it is difficult to reconstruct the decision-making processes involved, it is our suspicion that the cardiologists reviewed his recent angiogram and concluded that there was no lesion that would be amenable to stent placement or dilatation.

This case is a reminder that it is vital to look at the entire clinical picture: the history, signs and symptoms of the patient, as well as his or her functional status, along with the results of an angiogram, if one has been obtained. This is particularly important before a cardiac cause of chest pain is excluded. In retrospect, the extent of compromise of our patient's coronary vessels probably would have been discovered by further testing of his functional capacity, e.g. , by a dobutamine stress echocardiogram or an adenosine–thallium scan.

In this instance, coronary intravascular ultrasound may have been a superior diagnostic test since it provides images not only of the lumen, but also of the vessel wall, including the plaque. 1,4,23The American College of Cardiology/American Heart Association guidelines for coronary angiography recommend coronary intravascular ultrasound as an alternative imaging modality for the evaluation of patients with characteristic anginal symptoms and positive results of a functional study, with no focal stenosis, or with only mild coronary artery disease on angiography. 24Another advantage of intravascular ultrasound over angiography is that it has the potential to detect soft, eccentric, lipid-rich plaques that may not be causing significant stenoses. 25These lesions may be more likely to be implicated in acute coronary syndromes as a result of acute plaque rupture and vessel occlusion. 8,26However, expense and availability may limit widespread use of this diagnostic tool at present. Furthermore, intravascular ultrasound requires instrumentation of the coronary artery and carries with it the associated risk of arterial damage or spasm. This report emphasizes that although coronary angiography is considered the best clinical tool to detect coronary atherosclerosis, it has limitations and must be used in conjunction with all other pertinent data.

The authors wish to thank Marjorie R. Grafe, M.D., Ph.D. (Professor and Vice-Chair, Department of Pathology, The University of Texas Medical Branch, Galveston, Texas), for her valuable assistance in providing the photomicrographs in this article.

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