Variant angina associated with isolated myocardial bridging: evaluation using intravascular ultrasound and quantitative coronary angiography

Variant angina, first described by Prinzmetal et al¹ in 1959, is hypothesized to be caused by transient coronary vasospasm at the site of an atherosclerotic plaque and leading to repetitive episodes of transmural myocardial ischemia. Myocardial bridging, a congenital coronary abnormality, is defined as a segment of a major epicardial coronary artery running intramurally through the myocardium.² The association of variant angina and isolated myocardial bridging is very uncommon. A review of the literature reveals only one case report indicating a causal relationship between the two diseases.³ We present an additional case who experienced Prinzmetal variant angina related to isolated myocardial bridging of the left anterior descending coronary artery (LAD), which was evaluated with intravascular ultrasound and quantitative coronary angiography.

A 48-year-old woman with a history of hypertension was referred for investigation of repeated chest discomfort for about 1 year. Her symptom was not related to physical effort and the duration of each episode was about several minutes. A resting electrocardiogram (ECG) was normal at the initial presentation. A treadmill exercise test and a 24-hour Holter monitor did not yet disclose any signs of myocardial ischemia. At one early morning during the hospitalization, she complained of severe squeezing retrosternal chest pain. Upon evaluation, the 12-lead ECG revealed 1－3 mm ST-segment elevation in the V2－V6 precordial leads. After intravenous administration of nitroglycerin, the chest pain subsided and the ECG normalized about 15 minutes later. This episode did not result in raised creatine kinase MB and troponin T. And no decreased wall motion was detected by echocardiogram.

Emergency cardiac catheterization was performed and coronary angiography showed almost normal coronary arteries except for a myocardial bridge in the mid-portion of the LAD (Fig. 1). Quantitative angiographic measurement disclosed that the maximal systolic diameter reduction was 51.4% at the level of the myocardial bridge. In addition, there was a persistent diastolic diameter reduction of 38.7% even in late diastole.

Subsequently, an intravascular ultrasound study was performed after intracoronary administration of 200 µg nitroglycerin. An intravascular ultrasonic half moon phenomenon, which is highly specific for the existence of myocardial bridging,⁴ was seen surrounding the bridge segment in the mid-portion of the LAD both in systole and diastole. There was not any atheroma to be visualized throughout the LAD. The cross-sectional area in bridging segment was reduced during systole (4.3 mm²) and this reduction continued into the whole diastole (4.8 mm²). Compared with the adjacent referent segment, the diastolic lumen area of bridging segment could not get back to normal, even smaller than the lumen area of distal reference (8.0 mm², Fig. 2).

After thorough discussion, the patient opted for an optimized medical therapy regimen. She has been symptom free for the last 6 months with no chest pain and fairly good exercise tolerance on diltiazem.

DISCUSSION

Variant angina is characterized by angina secondary to coronary artery vasospasm,⁵ typically at rest, associated with transient ST-segment deviations.¹ Miyao et al⁶ have shown that coronary spasm tends to occur in areas with atherosclerotic lesions. The present case suffered from typical variant angina, but both coronary angiography and intracoronary ultrasound demonstrated that there were not any atherosclerotic lesions except for a myocardial bridge in the mid-LAD. Myocardial bridging has been traditionally considered as a benign condition. The true incidence is not known but has a wide range of up to 16% on angiography and up to 80% at autopsy.⁷ Although some reports^2,7 have shown myocardial bridging occasionally might result in cardiac events, the association of variant angina and isolated myocardial bridging was rarely reported.

In a previous study,⁸ coronary spasm, traditionally hypothesized to be the cause of variant angina, was demonstrated to be more common in patients with myocardial bridging than in those without it, especially in the bridging segments during spasm-provocation tests. And multivariate Logistic regression analysis showed that myocardial bridging was a predictor of coronary spasm. In the case reported by Munakata et al,³ coronary vasospasm was also provoked by acetylcholine at the identical portion of the coronary artery where only myocardial bridging was noted and there was no significant arteriosclerosis. All these findings suggested that coronary spasm might be a possible pathophy- siological mechanism of variant angina associated with myocardial bridging.

The relationship and respective roles of myocardial bridging and coronary vasospasm, however, remain uncertain. Systolic kinking of the vessels by myocardial bridges may cause trauma to the intima and damage to the endothelium, thereby evoking platelet aggregation and vasospasm.^9,10 A series of studies^11-13 have shown that vascular dysfunction at level of the endothelium and/or smooth muscle, which was reportedly involved in the genesis of coronary spasm,^14,15 might occur in bridging segments. Although definite proof of a relationship between myocardial bridging and vasospasm is still lacking, we suggest that vasospasm may play an important role, at least in some patients with myocardial bridging, in inducing and worsening myocardial ischemia.

REFERENCES

1. Prinzmetal M, Kennarmer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med 1959; 27: 375-388. [PubMed]

2. Mohlenkamp S, Hort W, Ge J, Erbel R. Update on myocardial bridging. Circulation 2002; 106: 2616-2622. [PubMed]

3. Munakata K, Sato N, Sasaki Y, Yasutake M, Kusama Y, Takayama M, et al. Two cases of variant form angina pectoris associated with myocardial bridge: a possible relationship among coronary vasospasm, atherosclerosis and myocardial bridge. Jpn Circ J 1992; 56: 1248-1252. [PubMed]

4. Ge J, Jeremias A, Rupp A, Abels M, Baumgart D, Liu F, et al. New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and Doppler. Eur Heart J 1999; 20: 1707-1716. [PubMed]

5. Maseri A, Pesola A, Marzilli M, Severi S, Parodi O, L'Abbate A, et al. Coronary vasospasm in angina pectoris. Lancet 1977; 1: 713-717.

6. Miyao Y, Kugiyama K, Kawano H, Motoyama T, Ogawa H, Yoshimura M, et al. Diffuse intimal thickening of coronary arteries in patients with coronary spastic angina. J Am Coll Cardiol 2000; 36:432-437.[PubMed]

7. Alegria JR, Herrmann J, Holmes DR Jr, Lerman A, Rihal CS. Myocardial bridging. Eur Heart J 2005; 26: 1159-1168. [PubMed]

8. Teragawa H, Fukuda Y, Matsuda K, Hirao H, Higashi Y, Yamagata T, et al. Myocardial bridging increases the risk of coronary spasm. Clin Cardiol 2003; 26:377-383. [PubMed]

9. Ciampricotti R, el Gamal M. Vasospastic coronary occlusion associated with a myocardial bridge. Cathet Cardiovasc Diagn 1988; 14:118-120. [PubMed]

10. Maseri A, Chierchia S. Coronary artery spasm: demonstration, definition, diagnosis, and consequences. Prog Cardiovasc Dis 1982; 25: 169-192. [PubMed]

11. Kuhn FE, Reagan K, Mohler ER III, Satler LF, Lu DY, Rackley CE. Evidence for endothelial dysfunction and enhanced vasoconstriction in myocardial bridges. Am Heart J 1991; 122:1764-1766. [PubMed]

12. Shiode N, Kato M, Teragawa H, Yamada T, Hirao H, Nomura K, et al. Vasomotility and nitric oxide bioactivity of the bridging segments of the left anterior descending coronary artery. Am J Cardiol 1998; 81:341-343.[PubMed]

13. Masuda T, Ishikawa Y, Akasaka Y, Itoh K, Kiguchi H, Ishii T. The effect of myocardial bridging of the coronary artery on vasoactive agents and atherosclerosis localization. J Pathol 2001; 193:408-414. [PubMed]

14. Kugiyama K, Yasue H, Okumura K. Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina. Circulation 1996; 94:266-272.[PubMed]

15. Egashira K, Inou T, Yamada A, Hirooka Y, Takeshita A. Preserved endothelium-dependent vasodilation at the vasospastic site in patients with variant angina. J Clin Invest 1992; 89:1047-1052. [PubMed]