Exercise-Induced Spastic Coronary Artery Occlusion at the Site of a Moderate Stenosis
Neither Prinzmetal's Angina nor Cardiac Syndrome X but “Prinzmetal X”
A 44-year-old man was referred to our hospital to undergo coronary angiography because of suspected coronary artery disease. For approximately 2 weeks, the patient had been experiencing typical symptoms of angina pectoris that occurred exclusively during physical exercise and predominantly in the morning hours when he bicycled to work. His general practitioner had performed a bicycle exercise test. In his written report, the practitioner noted that he suspected hemodynamically significant coronary artery disease because of reproduction of typical angina pectoris in addition to ischemic ECG changes.
On admission, the patient was in good general condition with no symptoms at rest. Coronary angiography revealed an ≈80% stenosis in the small right coronary artery and an ≈50% stenosis in the proximal segment of the left anterior descending artery (LAD), although systolic left ventricular function was normal (Figure 1). Fractional flow measurements (fractional flow reserve) were performed in the right coronary artery and the LAD and revealed a significantly impaired fractional flow reserve only in the right coronary artery (fractional flow reserve 70%) and not in the LAD (fractional flow reserve 85%). Thus, the right coronary artery stenosis was treated with a drug-eluting stent (Figure 1), and the patient was discharged on medical therapy.
Six weeks later, the patient was referred again to our department because of unchanged symptoms of exercise-induced typical angina pectoris. Again, his general practitioner had performed a bicycle exercise test and observed ischemic ECG changes accompanied by typical angina pectoris. Coronary angiography was repeated and revealed only minor lumen irregularities in the right coronary artery and an unchanged ≈50% stenosis in the proximal LAD (Figure 2). Because only stress echocardiography has a satisfactory diagnostic specificity for the detection of significant epicardial coronary artery disease in patients with potential microvascular disease,1 we decided to perform stress echocardiography the next day.
At the beginning of stress echocardiography (with bicycle exercise), the patient was free of any symptoms, and echocardiography demonstrated normal wall motion. At 50-W stress exposure, he began feeling some angina. Concurrently, his ECG demonstrated subtle ST-segment changes, whereas echocardiography revealed hypokinesis in the anteroseptal wall. At 75-W stress exposure, his symptoms and ECG changes increased rapidly and severely, and echocardiography demonstrated akinesis of the anteroseptal wall. Further aggravation of angina and ECG changes at 100 W of stress exposure forced us to stop the test. After stopping exercise, the patient recovered spontaneously and quickly, his ECG changes disappeared, and wall motion in the anteroseptal segments normalized (Figures 3A through 3D; full-motion Movies 1A through 1D in the online-only Data Supplement). Taken together, these findings were suggestive of exercise-induced transmural ischemia in the anteroseptal wall with reciprocal ST-segment depressions in the inferolateral leads. To identify the cause of this unusual presentation, it was decided to take the patient once more to the catheterization laboratory and perform a coronary vasomotion test with intracoronary acetylcholine provocation.
In the first angiogram of the left coronary artery, the proximal LAD stenosis appeared more narrowed (≈75%;Figure 4A) than in the prior angiograms. Even at the smallest dose of 2 μg of acetylcholine infused into the left coronary artery, severe vasoconstriction occurred at the site of the LAD stenosis, with impaired coronary blood flow distal to this stenosis (Figure 4B). Minor ECG changes were observed; however, the patient was still asymptomatic. At the next dose of 20 μg of acetylcholine, the LAD occluded completely at the site of the former stenosis (Figure 4C). At this time, severe ECG changes occurred, and the patient began to experience his usual angina pain. Therefore, 0.4 mg of nitroglycerin was injected into the left coronary artery, and after 2 minutes, the LAD occlusion disappeared, and the LAD stenosis was unmasked with only ≈50% remaining luminal occlusion (Figure 4D).
A coronary computed tomography study revealed a focal atheromatous plaque at the site of the LAD stenosis (Figure 5). Consequently, a diagnosis of exercise-induced spastic LAD occlusion at the site of an atheromatous plaque was made. The implantation of another stent at the site of this moderate LAD stenosis was weighed against an antispastic medical treatment with a calcium antagonist. It was decided to start an antispastic treatment with diltiazem 120 mg twice daily and to continue monitoring the patient as an inpatient.
Two days after medical treatment with diltiazem was started, stress echocardiography was repeated. At this time, workload could be increased stepwise up to 175 W, and the bicycle test only had to be terminated because lower-extremity muscle exhaustion occurred. The patient did not feel any chest discomfort throughout the test, and echocardiography demonstrated normal wall-motion behavior during all levels of stress exposure (Figures 6A through 6D; full-motion Movies 2A through 2D in the online-only Data Supplement). Thus, successful treatment of the exercise-induced spastic LAD occlusion was achieved with medical therapy.
Our results suggest that (1) the coronary wall at the site of an atheromatous plaque is not simply fixed and immobile but may even be hyperdynamic and cause spastic coronary occlusion in response to exercise; (2) assessment of luminal diameters only or performance of fractional flow reserve measurements (without physical exercise) does not allow the detection of dynamic exercise-induced coronary obstructions; and (3) dramatically improved stress test results may be obtained in such patients within a few days as a result of successful medical therapy. Currently used denotations such as Prinzmetal's angina2 or cardiac syndrome X3 do not really cover our observation of a strictly exercise-induced spastic occlusion of the LAD at the site of a moderate stenosis. Because this case resembles some aspects of Prinzmetal's angina and other aspects of cardiac syndrome X, we suggest calling such a pathophysiology “Prinzmetal X.”
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/122/23/e570/DC1.
- © 2010 American Heart Association, Inc.
- Fragasso G,
- Lu C,
- Dabrowski P,
- Pagnotta P,
- Sheiban I,
- Chierchia SL