A Casual versus Causal Relationship in Corona

Coronary anomalies continue to attract the interest of cardiologists, and the most frequent type of publication on this subject is the case report. A peculiar feature of such reports is that they typically imply that these abnormalities are a consistent class of pathogenic entities that cause ischemic consequences. If coronary anomalies were a clear pathogenic entity, being fairly common in the general population, one would expect their clinical manifestations to be easily identifiable and further case reports to be unnecessary. Unfortunately, coronary anomalies comprise many different entities, only a few of which have consistent clinical manifestations. Most reported cases require specific and critical review, because the association of anatomic abnormalities with clinical events might well be casual rather than causal, or indirect rather than direct.¹ In addition, other precipitating factors could be involved.

The case of the coronary anomaly reported by Aydin and colleagues² in this issue is one that requires objective, critical review. The diagnosis of the anatomic entity (anomalous origin of the left circumflex artery from the right coronary sinus with a retroaortic course) is well documented in the figures. Such a coronary anomaly is one of the most frequently observed abnormalities in the catheterization laboratory (seen in about 0.5% to 0.7% of the patients studied) and is often reported in the medical literature. The anomaly is generally considered benign and is not associated with ischemic manifestations. In Aydin's reported case, I believe that the patient's first presentation at age 73 years is unlikely to have been the result of an uncomplicated congenital anomaly, although that is possible. The dominant presenting symptom was dyspnea, which might also have been due to the patient's coexisting pulmonary condition and atrial fibrillation, with mild cardiomyopathy. Nuclear scintigraphy with dobutamine stress testing reportedly showed reversible ischemia of the inferior and basal septum—a territory supplied by the distal anomalous vessel, which had a dominant pattern (posterior descending artery from the circumflex artery). Of note, the anomalous vessel also supplied the territory of the obtuse margin, which appears to have had a normal blood supply on scintigraphy.

If the nuclear test results are correct, they would indicate an obstructive lesion of the distal anomalous circumflex artery but not of the proximal retroaortic portion (and not of the obtuse marginal branch). Reversible myocardial ischemia that occurs during a dobutamine test generally indicates a fixed obstruction of more than 70%. Such stenosis is not known to occur in an uncomplicated anomalous circumflex from the right sinus (even by intravascular imaging, in my experience), nor was it seen on the angiographic study presented here. Nonetheless, the authors propose that the coronary anomaly alone produced ischemia during dobutamine infusion, as a result of expansion of the aorta with compression of the circumflex artery. In my opinion, this is an unlikely mechanism, particularly in a 73-year-old patient with an atherosclerotic and apparently ectatic circumflex artery. In this anomaly, the ectopic vessel is not squeezed between any two hard structures, as is frequently claimed to occur in cases of anomalous origin from the opposite sinus with an anteroaortic course. Expansion of the aorta might cause minor displacement (and then only during systole) but would not obliterate the anomalous vessel.

The reported clinical improvement after the use of β-blockers and nitrates could be considered quite relevant and illuminating, because the patient's symptoms might have been caused by cardiomyopathy and atrial fibrillation, both of which can be improved by β-blocker usage. Unfortunately, the authors did not perform another dobutamine nuclear stress test under the new treatment regimen. The authors state that “because the symptoms completely resolved after β-blocker treatment, we did not need to confirm improvement.” This case report would have been strengthened considerably by the presentation of objective evidence of the patient's improvement.

Coronary anomalies that are generally considered benign may indeed cause ischemia by some unusual mechanism that requires objective study and documentation, possibly in the presence of

• Extreme variation of the anomaly itself (as when it is accompanied by a tangential origin of the ectopic artery, with intussusception, which is usually not present in the reported anomaly);³

• An unusual aortic root–ectopic coronary artery relationship with external compression (which has not yet been documented and cannot be accepted if not proved by intravascular ultrasound);

• A superimposed obstructive, thrombotic, or atherosclerotic lesion. Sometimes it is necessary to use intravascular ultrasound, a pressure wire, or a Doppler wire to reach definite conclusions in this regard.

When an observer can document a pathophysiologic mechanism in a patient with a coronary anomaly, he or she should strive to document ischemia by objective methods. In the exceptional situation in which an intervention of any kind might be carried out in order to eliminate the presenting ischemic manifestations, objective evidence of its effect should still be sought. In the present case, the mechanism might have been confirmed by repeating the study after withholding the clinically effective medication.

Investigators of coronary anomalies are encouraged to maintain a critical attitude in their approach. Our investigative group assesses coronary anomalies with ischemic potential by 1) describing them precisely (in an effort to establish the geometric severity of the stenosis), frequently by the use of newer imaging technologies such as intravascular ultrasound; 2) performing challenge tests, usually pharmacologic, that may have predictive value; 3) establishing a database to enable longitudinal studies of the prognostic implications; and 4) performing close follow-up after pharmacologic treatment or any revascularization procedure, with the intent of confirming the effectiveness of the approach and the clinical implications of the results.^3,4

Multicenter, cooperative, and prospective studies of large series of patients are the ideal way in which to clarify our persistently nebulous knowledge of coronary anomalies, and should be encouraged.