Vasospasm-induced acute myocardial infarction—Thrombus formation without thrombogenic lesion at the culprit

Abstract

Although plaque rupture is the major cause of acute myocardial infarction, vasospasm is also known as a potential cause of acute myocardial infarction. However, it is very rare and is sometimes difficult to diagnose correctly. A 30-year-old male patient with suspected unstable angina pectoris who received catheterization in 1999 had normal coronary artery but positive result in the provocation test of vasospasm. Although his angina had been suppressed by medications, he suffered ST-elevation acute myocardial infarction after the discontinuation of medication. The initial angiogram showed total occlusion of the proximal left anterior descending coronary artery. Thrombolysis and nitroglycerin achieved recanalization of the culprit lesion with only mild residual stenosis. Angioscopy revealed normal white luminal wall without any thrombogenic lesion. Therefore, the cause of coronary occlusion was diagnosed as vasospasm. However, since the repeated vasospastic occlusion of the culprit lesion regardless of repeated intra-coronary injection of nitroglycerin was observed, a stent was implanted and vasospasm was successfully prevented. It is not easy to judge from the angiogram that the cause of coronary occlusion in the patients with acute myocardial infarction is vasospasm. It is important to think routinely about the possibility of vasospasm as a cause of acute myocardial infarction.

<Learning objective: In a patient with acute myocardial infarction caused by vasospasm, angioscopy revealed normal white luminal vessel wall without any thrombogenic lesion at the culprit, although the initial angiogram suggested the presence of thrombus. It is not easy to judge from the angiogram that the cause of coronary occlusion in the patients with acute myocardial infarction is vasospasm.>

Introduction

Although plaque rupture is the major cause of acute myocardial infarction, vasospasm is also known as a potential cause of acute myocardial infarction [1]. However, it is very rare and is sometimes difficult to diagnose correctly. The third universal definition of myocardial infarction classified spontaneous myocardial infarction due to plaque rupture as type 1 and the myocardial infarction caused by vasospasm as type 2. We would like to present a case in which vasospasm was clinically confirmed as the cause of acute myocardial infarction.

Case report

A 30-year-old male patient with suspected unstable angina pectoris received catheterization in 1999. He had chest pain at rest lasting for about 5–10 min mainly in the morning since a week previously. The 12-lead electrocardiogram and ultrasound cardiogram on admission were normal. He was a current smoker and had untreated hypertension. He did not have diabetes mellitus, dyslipidemia, or chronic kidney disease. The coronary angiography revealed no significant stenosis (Fig. 1). Since there was no significant coronary stenosis consistent as the culprit of unstable angina, acetylcholine provocation test was performed. Intra-coronary administration of 50 μg acetylcholine to the left coronary artery induced chest pain and ST elevation in the anterior leads. The chest pain resembled his natural symptoms. Coronary angiography revealed diffuse spasm both in the left anterior descending coronary artery and in the circumflex coronary artery on the first right anterior oblique-caudal view (Fig. 2A), and severe spasm in the proximal segment of the left anterior descending coronary artery on the next left anterior oblique-cranial view (Fig. 2B), which was relieved after repeated intra-coronary injection of nitroglycerine. Therefore, the patient was diagnosed to have vasospastic angina and was treated with an oral nitrate and calcium channel blocker (40 mg isosorbide dinitrate, 15 mg nicorandil, and 10 mg amlodipine besilate). He quitted smoking thereafter.

Fig. 1.

Coronary angiogram at the time of unstable angina. The catheterization was performed for a 30-year-old male patient with suspected unstable angina pectoris in 1999. However, the coronary angiography revealed no significant stenosis: (A) left coronary artery and (B) right coronary artery.

Fig. 2.

Acetylcholine provocation test. Intra-coronary administration of 50 μg acetylcholine to the left coronary artery induced chest pain and ST elevation in the anterior leads. The chest pain resembled his natural symptoms. Coronary angiography revealed diffuse spasm (yellow arrows) both in the left anterior descending coronary artery and in the circumflex coronary artery on the first right anterior oblique-caudal view (A), and severe spasm (red arrow) in the proximal segment of the left anterior descending coronary artery on the next left anterior oblique-cranial view (B), which was relieved after repeated intra-coronary injection of nitroglycerine. Therefore, the patient was diagnosed to have vasospastic angina. (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)

Since he had no angina attack for about 5 months, he stopped taking medications by himself. As he had severe chest pain at rest that lasted for an hour, he came to the emergency department of our hospital. He had not been taking medications for about one week. ST elevation was detected in the anterior leads of the electrocardiogram (Fig. 3A). Diagnosed as ST-elevation acute myocardial infarction, emergent catheterization was performed. The initial angiogram revealed total occlusion of the proximal segment in the left anterior descending coronary artery (Fig. 3B and C). Since the presence of massive thrombus was suspected from the angiogram, thrombolysis was performed. After thrombolysis with tissue plasminogen activator and intra-coronary nitroglycerin administration, the angiogram showed mild to moderate residual stenosis (Fig. 4A). However, since the culprit lesion occluded again soon (Fig. 4B), balloon dilatation was performed. Repeated balloon inflation was required for the repeated occlusion of the lesion. Therefore, we performed angioscopic examination to clarify the pathophysiology of the disease. Angioscopy identified white smooth vessel wall without any thrombogenic (thrombus-adhering) lesion at the culprit lesion (Fig. 4C). No ruptured plaque, yellow plaque, or thrombus-adhering site suggestive of plaque erosion was detected. Although we administered intra-coronary nitroglycerin repeatedly and performed balloon inflation repeatedly, the occlusion of the culprit lesion was not completely prevented. The vasospastic occlusion occurred repeatedly at the same short culprit segment. Therefore, we implanted a bare metal stent of 3.5 mm × 16 mm and successfully prevented the spastic occlusion of the culprit lesion (Fig. 5A). The patient had no angina attack thereafter with the same anti-angina medications as before and dual anti-platelet therapy (aspirin and ticlopidine). At 6-month follow-up angiography, no significant in-stent restenosis was detected and only mild narrowing was detected at the proximal edge of the stent (Fig. 5B).

Fig. 3.

Initial coronary angiogram at the time of acute myocardial infarction. As the patient had severe chest pain at rest that lasted for an hour, he came to the emergency department of our hospital. Diagnosed with ST-elevation acute myocardial infarction by the electrocardiogram showing ST elevation in V₁ to V₄ and _aV_L leads with ST depression in II, III, _aV_F leads (A), emergent catheterization was performed. The initial angiogram (B) revealed total occlusion (thrombolysis in myocardial infarction grade 1) at the proximal segment of the left anterior descending coronary artery (red arrow). Since the presence of massive thrombus was suspected on the angiogram (C, magnified image of the culprit), thrombolysis was performed. (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4.

The angiogram and angioscopy after thrombolysis. After thrombolysis with tissue plasminogen activator and intra-coronary nitroglycerin administration, the angiogram showed mild to moderate residual stenosis (A). However, since the culprit lesion occluded again soon (B), balloon dilatation was performed. Repeated balloon inflation was required for the repeated occlusion of the lesion. Angioscopy identified white smooth vessel wall without any thrombogenic (thrombus-adhering) lesion at the culprit (C). No ruptured plaque, yellow plaque, or thrombus-adhering site suggestive of plaque erosion was detected. Therefore, in this case, the repeated occlusion of the culprit and thus acute myocardial infarction was supposed to be caused by vasospasm. (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 5.

Stenting at the culprit and 6-month follow-up. Although we administered intra-coronary nitroglycerin repeatedly, the occlusion of the culprit was not completely prevented. Therefore, we implanted a bare metal stent of 3.5 mm × 16 mm (blue line with arrows) and successfully prevented the spastic occlusion of the culprit (A). The patient had no angina attack thereafter with oral medications. By the 6-month follow-up angiography (B), no significant in-stent restenosis was detected and only mild narrowing was detected at the proximal edge of the stent (yellow arrow). (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)

Discussion

This patient had been diagnosed as having vasospastic angina using the acetylcholine provocation test before the onset of myocardial infarction. Acute myocardial infarction occurred after the discontinuation of anti-vasospastic medications; and the culprit lesion was the site where acetylcholine provocation test induced severe vasospasm. Although this case had vasospastic angina, we initially thought plaque rupture with thrombus formation might be the cause of acute myocardial infarction judging from the angiogram. However, although the presence of thrombus was suspected on the initial angiogram, the absence of ruptured yellow plaque and thrombus-adhering lesion was confirmed by angioscopy. According to our previous study with angioscopy [2], thrombus and disrupted yellow plaque is usually detected at the culprit of acute myocardial infarction even after thrombolysis. Therefore, in this case without disrupted yellow plaque or thrombus adhesion, the repeated occlusion of the culprit lesion and thus acute myocardial infarction was supposed to be caused by vasospasm. In young patients with acute myocardial infarction [3], the culprit lesion sometimes looks white but usually has thrombus adhesion (Fig. 6), which is compatible with the pathologically demonstrated culprit lesion of acute myocardial infarction with plaque erosion but without necrotic core. Therefore, lacking thrombus-adhering lesion suggestive of plaque erosion, vasospastic occlusion of coronary artery might be the cause of secondary thrombus formation in this case. There is a limitation that angioscopy cannot always observe the whole vessel wall and may miss some thrombogenic lesion. However, in the present case, angioscopic image was good enough to evaluate the culprit segment.

Fig. 6.

The culprit of acute myocardial infarction in young patients (from Ueda et al. [3]). According to our previous report, the culprit of acute myocardial infarction in young (<50 years old) patients had disrupted yellow plaque in 70% of cases (A) but did not have yellow plaque and looked white in 30% of cases (B), although both types of lesions had thrombus adhesion. This white thrombogenic lesion is compatible with histologically reported plaque erosion that does not have necrotic core. Both of these disrupted yellow plaques (A) and white lesions (B) are thrombogenic and are the causes of thrombotic coronary occlusion, while we did not detect any thrombogenic lesion at the culprit in the present case. (For interpretation of references to color in this figure legend, the reader is referred to the web version of this article.)

Although thrombolysis and balloon angioplasty was performed before stenting in this case, we might have lost the chance to suspect vasospasm as the cause of myocardial infarction if direct stenting was performed. Therefore, some of the cases with acute myocardial infarction we have treated by direct stenting might have been caused by vasospasm. The intravascular ultrasound imaging after thrombus aspiration may give us the suggestion that the case might be caused by vasospasm; however, angioscopy would be required to confirm the absence of thrombogenic lesion. We stented the culprit lesion because the repeated coronary occlusion by vasospasm could not be prevented by medications and balloon inflations in this case; however, in general, we think we can avoid stenting in the majority of cases with acute myocardial infarction caused by vasospasm. In the present case, repeated balloon inflation might have caused vessel injury and increased the vasospastic response of the vessel. According to a review [4], approximately 20% of patients with coronary artery vasospasm remain refractory to medical therapy and require further treatment mainly by stenting, although the treatment by stenting has limitations of in-stent restenosis and coronary spasm recurrence proximal or distal to the stent. Although calcium channel blockers are strong anti-vasospastic medication, their effectiveness to prevent vasospasm may be different among different drugs, e.g. benidipine has been reported to have better beneficial effect than some other calcium channel blockers [5]. It is important to think routinely about the possibility of vasospasm as a cause of acute myocardial infarction and avoid unnecessary stenting. Although unnecessary stenting should be determined by clinical trials, if reperfusion without residual severe stenosis is achieved by thrombus aspiration and vasodilator infusion alone in the cases without thrombogenic lesion at the culprit, we believe stenting would not be required.

Conclusion

It is not easy to judge from the angiogram that the cause of coronary occlusion in patients with acute myocardial infarction is vasospasm.