Stent Implantation for Diffuse and Multiple Coronary Spasm
in a Patient with Variant Angina Refractory to Optimal Medical
Ther
Variant angina is more frequently seen in East Asia than in the West. It may be associated with acute myocardial infarction, severe cardiac arrhythmia and sudden death. Most patients obtain sufficient relief by vasodilator drug management such as calcium antagonists and/or nitrates. However, it is well known that some patients experience angina refractory to such treatments.1,2 Reportedly, about 5–30% of patients with variant angina do not get relief from anginal attacks with medical management. Previous studies showed that stent placement in spastic segments might be helpful for these patients.3–6 However, these reports are limited to treatment of discrete and proximal fixed obstructive coronary artery lesions. Here, we report a case of multiple and diffuse spasm without coronary stenosis that resolved with full-coverage stent implantation.
Case Report. A 72-year-old male presented with occasional chest pain lasting for about 30 minutes in the early morning since April 2003. Chest pain occurred once or twice a month, but the duration of chest pain became longer and more frequent around December 2005. The patient had a history of high blood pressure and heavy cigarette smoking and was not taking any medication.
He consulted a cardiologist in a local hospital on February 2006. Holter monitoring was performed and during an episode of chest pain, it showed ST-segment elevation in the NASA (V2) lead and reciprocal change in the CC5 (V5) lead (Figure 1). The cardiologist at the hospital diagnosed him with variant angina and prescribed 2 vasodilatory agents. Despite medical management with these drugs, his chest pain was not relieved. Subsequently, the vasodilatory drugs were increased to the maximal dosages allowed by Japanese regulation as follows: nifedipine L 40 mg, diltiazem R 400 mg, nicorandil 15 mg, doxazosin 4 mg, and nitroglycerin TTS 1 pill per day. However, the patient’s variant angina was resistant to the vasodilatory therapy. Furthermore, an adverse skin reaction was observed on March 2006, probably caused by the calcium antagonists. Despite this, the cardiologist considered that treatment with calcium antagonist should continue because of the patient’s frequent chest pain.
The patient was referred to our hospital on June 2006. His heart sounds were normal without murmurs, rubs or gallops. Electrocardiography showed no ST-T-segment changes during the asymptomatic phase. Chest X-ray showed no significant abnormality. Echocardiography demonstrated normal left ventricular contraction without valvular abnormality.
Coronary angiography revealed no significant coronary stenosis. Subsequently, a challenge test was performed with intracoronary acetylcholine injection. In our protocol for challenge tests, acetylcholine injection is infused into a coronary artery in incremental doses of 20, 50, 100 μg (up to 100 μg for the left coronary artery and 50 μg for the right coronary artery [RCA]) and a temporary pacemaker was inserted into the right ventricle to prevent bradycardia which is usually associated with acetylcholine.7 Subtotal occlusions with ST-segment elevation due to multiple and diffuse spasm were provoked at the RCA and the left anterior descending artery (LAD). The left circumflex coronary artery (LCX) was free from spasm. Stent implantation was attempted to mechanically prevent spastic coronary occlusion. Two stents (Duraflex™ 3.5 x 25 mm and 3.5 x 18 mm, Goodman, Japan) were implanted at the proximal-to-mid portion of the RCA and post-implantation ballooning was performed until we confirmed adequate stent expansion by intravascular ultrasound (IVUS). A second challenge test showed no spasm at the stented areas, but spasm was still provoked with ST-segment elevation in the distal portion of the RCA. A 3.0 x 18 mmDuraflex stent was placed in the spastic segment at the distal portion. The third challenge test showed that spasm had not been provoked at the RCA (Figure 2).
Next, we implanted a 3.0 x 18 mm Duraflex stent to the mid portion of the LAD that showed spasm during the challenge test. The second LAD challenge test showed no spasm at the stented area, but spasm was still provoked with ST-segment elevation at the distal LAD. A 2.5 x 20 mm Tsunami™ (Terumo, Japan) was implanted in the distal LAD. Spasm was not provoked by the third challenge test with full-dose of acetylcholine in the patient’s left coronary arteries (Figure 3).
After the interventional therapy, calcium antagonists were discontinued. The patient’s skin reaction also resolved after the discontinuation of calcium antagonist. At 8 months post-stent implantation, the patient was well without symptoms of cardiac ischemia under the administration of nitrates alone.
Discussion. The majority of patients with variant angina can be treated successfully with medication and tend to experience more benign courses than patients with associated severe obstructive lesions.8 Calcium antagonists and nitrates are the first-line drugs used to relieve variant angina. Other than these drugs, alpha adrenoreceptor-blockers relieve refractory variant angina.9 Nicorandil appears to be effective for the treatment of vasospastic angina.10 Troglitazone reduces the frequency of variant angina and improves endothelial function in patients with diabetes mellitus.11 On the other hand, angiotensin-converting enzyme inhibitors are often of therapeutic value in acute myocardial infarction, but are ineffective in variant angina.12 Despite the use of medications that are usually effective, this patient experienced frequent chest pain.
Previous reports showed that percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) might be helpful in patients with variant angina with fixed obstructive lesions.3,4,13 However, PCI and stenting for patients with variant angina have not been recommendeddue to the possibility of spasm at a site different from the initial stenosis.4 Gaspardone et al showed that 33% of variant angina patients who underwent PCI experienced recurrent anginal attacks and spasm was provoked at a different site from the previously stented segment.3 Recurrence of variant angina at another site might be the biggest problem associated with this interventional approach. In our case, we repeated the challenge test several times, and if spasm occurred at a different site, additional stents were implanted at the new spasm-provoked segment. Finally, we confirmed that spasm was not provoked at any site in his coronary arteries. We considered that this strategy prevented the recurrence of variant angina in this case.
One of the limitations in this therapy is in-stent restenosis.5,14 The other limitations of this approach include stent thrombosis. Stent thrombosis is related to undesirable outcomes with higher mortality. Generally, sufficient antiplatelet therapy can reduce the incidence of stent thrombosis to approximately 0.5%.15 In addition, previous studies have shown that adequate stent expansion reduces the incidence of stent thrombosis.16 Balloon inflation was repeated after stent implantation until we confirmed adequate stent expansion by IVUS. From this perspective, selecting baremetal stents for this patient may have had a potential advantage compared with drug-eluting stents.17
There is no consensus about the optimal treatment for variant angina with diffuse and multiple spasm refractory to medical treatment. We don’t believe that this therapy is the primary therapy for variant angina patients, but it could be a strategic option for patients who refractory to maximumdose medical therapy. Some limitations remained in interventional approaches including potential adverse outcomes in association with stent thrombosis, in-stent restenosis and recurrence of vasospasm at a different site from the stented segments. Therefore, the indication for this therapy must be carefully considered based on the characteristics of each patient. Further investigation is necessary before this approach can be generalized.
Conclusion. We reported a case of variant angina with diffuse and multiple spasm refractory to treatment with medication that was successfully resolved by full-coverage bare-metal stenting of the spastic segments. Repeating the challenge tests was helpful for adequate positioning of the stents. Stent implantation could be a strategic option for patients with variant angina refractory to full-dose medical therapy.
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