Coronary Artery Spasm Associated with a Moderately Severe Atherosclerotic Stenosis in the Proximal LAD

Coronary artery spasm was first described by Prinzmetal in 19591 as a variant form of angina that occurred predominantly at rest and was usually associated with ST-segment elevation on the electrocardiogram (ECG). The angina and ST-segment elevation are caused by an occlusive or subocclusive epicardial coronary artery that has undergone spasm.2 Coronary artery spasm is localized to a segment of epicardial coronary artery and is thought to occur at the site of an atherosclerotic plaque.3 Treatment of coronary artery spasm can be difficult; significant fractions of patients (up to 25%) continue to have episodes of chest pain despite maximal therapy with calcium antagonists and nitrates.4,5 These episodes can lead to myocardial infarction and even death. The prognosis is worse for patients who have spasm superimposed on an atherosclerotic narrowing and if tachy- or bradyarrhythmias occur during the pain episodes.3 Percutaneous coronary interventions with balloon angioplasty and more recently with coronary artery stenting have been reported in case studies and small case series for the treatment of variant angina that was unresponsive to medical therapy.6–11 Stenting appeared to be superior to percutaneous transluminal coronary angioplasty for these medically unresponsive patients, but it was not successful inhibiting spasm in approximately 30% of treated subjects.8–11 In the unsuccessful patients, spasm was either never relieved because of “migration” distal or proximal to the stent, or it was “cured”, only to return when in-stent restenosis occurred and extended beyond the stent. We report on the case of a female with coronary artery spasm associated with a mild atherosclerotic plaque of the proximal left anterior descending (LAD) coronary artery. Case Report. A 42-year-old female patient with a 3-month history of angina that responded to sublingual nitrates presented to the emergency room with severe, prolonged substernal chest discomfort that had not resolved after 30 minutes and 3 sublingual nitroglycerine tablets. The chest pain resolved in the emergency department with oxygen and additional sublingual nitroglycerine. A 12-lead ECG taken just after the episode of pain was normal. The working diagnosis was acute coronary syndrome or esophageal spasm. The patient was admitted and placed on aspirin, intravenous heparin and glycerol-trinitrate. Her regular therapy with atenolol 50 mg once daily was continued. Subsequent serial ECGs and cardiac enzymes were within normal limits. The patient had 5 further episodes of chest pain in the next 24 hours despite therapeutic heparin (aPTT = 72 seconds) and high-dose intravenous glycerol-trinitrate. Due to prompt pain relief with sublingual nitroglycerine and intravenous morphine, no ECGs were performed while the patient had chest pain. ECGs taken after the episodes of pain were within normal limits. Given the repeated clinical events, she was referred for cardiac catheterization and angiography. Diagnostic 6 French (Fr) coronary angiography revealed a normal left main coronary artery, 90% stenosis in the proximal LAD, 25% stenosis in the proximal circumflex coronary artery (Figure 1A) and a normal right coronary artery. During the initial left-sided injections, the patient developed severe central chest pain and arterial pressure rose to 190/100 mmHg. ST-segment elevation was noted on the ECG rhythm strip in lead I. Intracoronary nitroglycerin (200 µg) was injected into the left main coronary artery. Subsequent contrast injections showed the proximal LAD stenosis had reduced to approximately 30–40% and the patient quickly became pain-free (Figure 1B). The ventriculogram (right anterior oblique view) showed normal left ventricular function with normal wall motion. The LAD lesion was imaged with intravascular ultrasound (IVUS; Boston Scientific Atlantis, Maple Grove, Minnesota) and 5,000 U of intra-arterial heparin were administered. The LAD lesion was crossed with a 0.014´´ guidewire using a 6 Fr Cordis XB 3.5 guide with side-holes (Cordis Corporation, Miami, Florida) (Figure 2). The lesion had a moderate-sized lipid pool with a thick overlying fibrous cap and had mild calcification (Figure 2A). The IVUS minimal luminal diameter (MLD) was 2.7 mm, minimal cross sectional area was 10.7 mm2 and area stenosis was 50%. The proximal circumflex lesion was then imaged with IVUS; it consisted of a small lipid pool with a thin overlying fibrous cap and no apparent calcification. It had an MLD of 2.8 mm, lesion cross-sectional area of 9.3 mm2 and area stenosis of 44%. Given that the IVUS showed that the lesions were non-obstructive and not vulnerable to rupture, no percutaneous coronary intervention was performed and the patient was recommended for medical management. The atenolol therapy was discontinued. She was commenced on diltiazem and isosorbide mononitrate and the doses were titrated up over the following 3 days. Her medications on discharge were slow-release diltiazem 120 mg po bid, isosorbide mononitrate 90 mg po qd, atorvastatin 40 mg po qd and aspirin 325 mg po qd. She had no further episodes of chest pain in the 3 months after the hospital admission. Discussion. Coronary artery spasm can occur in angiographically normal coronary arteries, but usually occurs at the site of an atherosclerotic plaque.3 In patients with no atherosclerotic plaque, or mild to moderate obstructive coronary artery stenoses, the currently accepted therapy is medical management with nitrates and calcium antagonists.11 In patients with coronary artery spasm that is refractory to medical management, coronary artery stenting may be an alternative. Two case series showed stenting to be effective. In the series by Marzilli et al., four patients with reproducible coronary artery spasm that had failed medical management received a Palmaz-Schatz stent or Gianturco-Roubin stent.10 At 1-month follow-up, all patients were asymptomatic. In a larger series by Gaspardone et al., nine consecutive patients with variant angina and recurrent attacks had angiograms that showed coronary artery spasm at the level of a mild to moderate atherosclerotic lesion despite medical therapy.11 All patients had coronary stents successfully implanted to cover the lesion that was associated with spasm. Mean follow-up was 10 ± 4 months (range, 6–14 months). Six patients remained asymptomatic with Holter monitoring negative for episodes of silent ischemia. Three patients had reoccurrence of their symptoms (all at 1–2 months) associated with ST-segment elevation on Holter monitor. An increase in their medical therapy was successful in all 3 cases. All patients had a 6-month follow-up coronary angiogram and in-stent restenosis occurred in 1 patient, who was asymptomatic. The use of IVUS in the present case was useful to better define the proximal LAD stenosis. A nonobstructive lesion was detected, which consisted predominantly of a thick fibrous cap with a moderate-sized lipid pool and no evidence of plaque fissuring or hemorrhage. The decision not to proceed with stent implantation was made on the basis of the following: 1) the patient had not had a trial of appropriate medical therapy for spasm (calcium antagonists and nitrates); 2) atenolol therapy might have promoted spasm; and 3) the lesion was neither vulnerable nor obstructive when spasm-free. Currently, stenting for coronary artery spasm bears the potential for in-stent restenosis and recurrent spasm proximal or distal to the stent.11,13 Coated stents with the capacity to elute antiproliferative agents, such as rapamycin (sirolimus) or paclitaxel (Taxol), have been shown to be effective in almost eliminating restenosis.14 These devices may make the decision to implant a stent at a moderately obstructive atherosclerotic lesion that is associated with coronary spasm safer without the limitation of in-stent restenosis. In conclusion, our patient with coronary artery spasm associated with a non-obstructive atherosclerotic proximal LAD stenosis was successfully treated by maximizing medical therapy consisting of nitrates and calcium antagonists after discontinuation of b-blocker therapy. Coronary artery stenting remains a future option if the patient fails medical management and has either recurrent spasm or more severe atherosclerotic coronary artery disease.

1. Prinzmetal M, Kennamer R, et al. Angina pectoris: A variant form of angina pectoris. Am J Med 1959;27:375–388. 2. Meller J, Pichard A, Dack S. Coronary arterial spasm in Prinzmetal’s angina: A proved hypothesis. Am J Cardiol 1976;37:938–940. 3. Waters DD, Miller DD, Szlachcic J, et al. Factors influencing the long-term prognosis of treated patients with variant angina. Circulation 1983;68:258–265. 4. Nakamura M, Takeshita A, Nose Y. Clinical characteristics associated with myocardial infarction, arrhythmias and sudden death in patients with vasospastic angina. Circulation 1987;75:1110–1116. 5. Freedman SB, Richmond DR, Alwyn M, Kelly DT. Late follow-up (41 to 102 months) of medically treated patients with coronary artery spasm and minor atherosclerotic coronary obstructions. Am J Cardiol 1986;57:1261–1263. 6. David PR, Waters DD, Scholl JM, et al. Percutaneous transluminal coronary angioplasty in patients with variant angina. Circulation 1982;66:695–702. 7. Bertrand ME, LaBlanche JM, Thieuleux FA, et al. Comparative results of percutaneous transluminal coronary angioplasty in patients with dynamic versus fixed coronary stenosis. J Am Coll Cardiol 1986;8:504–508. 8. Lopez JA, Angelini P, Leachman DR, Lufschanowski R. Gianturco-Roubin stent placement for variant angina refractory to medical treatment. Cathet Cardiovasc Diagn 1994;33:161–165. 9. Nakamura T, Furukawa K, Uchiyama H, et al. Stent placement for recurrent vasospastic angina resistant to medical treatment. Cathet Cardiovasc Diagn 1997;42:440–443. 10. Marzilli M, Sabbadini G, Fedele S, et al. Coronary stenting for Prinzmetal’s angina. Circulation 1996;94:I-454. 11. Gaspardone A, Tomai F, Versaci F, et al. Coronary artery stent placement in patients with variant angina refractory to medical treatment. Am J Cardiol 1999;84:96–8, A8. 12. Lefroy D, Crake T, Haider AW, Maseri A. Medical treatment of refractory coronary artery spasm. Cor Art Dis 1992;3:745–752. 13. Rabinowitz A, Dodek A, Carere RG, Webb JG. Stenting for treatment of coronary vasospasm. Cathet Cardiovasc Diagn 1996;39:372–375. 14. Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: A quantitative coronary angiography and three-dimensional intravascular ultrasound study. Circulation 2001;103:192–195.