The potential hazard of drug-eluting stent-induced coronary vasospasm causing subacute stent thrombosis: a case report
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Drug-eluting stent (DES) -induced coronary vasospasm is a well known phenomenon after stent implantation; however, the extent of this risk is still unknown. We report a case in which DES-induced severe coronary vasospasm was clinically suspected as a cause of subacute stent thrombosis (ST).
A 67-year-old man came to our hospital due to chest pain with mild exercise. He was diagnosed with effort angina by coronary angiography and underwent DES implantation in the mid-left ascending artery (LAD) after the administration of dual anti-platelet therapy. The procedure was uneventful, but his symptoms changed from effort angina to rest angina after stenting. Five days after the procedure, subacute ST occurred, requiring aspiration thrombectomy and balloon angioplasty. Thereafter, he continued to report early morning chest discomfort. We performed a spasm provocation test to evaluate the coronary vasomotor response; it revealed severe stent-edge spasm in the left main trunk to the LAD, except for the stented lesion, and total occlusion of the left circumflex artery.
To our knowledge, the present case is the first report describing in-stent thrombosis secondary to stent-edge spasm. This case describes the potential hazard of DES-induced coronary vasospasm. Although there are several overlapping risk factors for ST development, we consider that stent-edge spasm also plays an important role in ST development. Therefore, we should monitor new-onset rest angina after stent implantation and carefully assess DES-induced coronary vasospasm.
KeywordsPercutaneous coronary intervention Effort angina Vasospastic angina Stent-edge spasm In-stent thrombosis
Cytochrome P450 2C19
Dual anti-platelet therapy
Left ascending artery
Left circumflex artery
Left main trunk
Percutaneous coronary intervention
Coronary vasospastic angina
Although drug-eluting stents (DES) reduce restenosis after percutaneous coronary intervention (PCI) more effectively than bare-metal stents (BMS), there are a variety of DES-related complications, such as coronary artery vasospasm. Some reports have suggested that endothelial dysfunction and enhanced vascular smooth muscle contractility with the involvement of the Rho-kinase pathway play an important role in the pathogenesis of DES-induced coronary vasospasm [1, 2]. Coronary vasospasm increases the risk of life-threatening cardiovascular events. An inability to administer adjunctive medical treatment for DES-induced coronary vasospasm after stent implantation promotes the coagulation system and thrombus formation, which may result in acute myocardial infarction [3, 4]. Here, we present a case in which DES-induced severe coronary vasospasm was clinically suspected as a cause of subacute stent thrombosis (ST).
We experienced a case of DES-induced severe coronary vasospasm, which may have contributed to the development of subacute ST. Although single stenting of the LMT showed a comparable clinical outcome compared to two-stent strategy , in this case, the intravascular ultrasound on initial PCI showed no significant stenosis in the LMT and we deployed DES only in the LAD lesion. In addition, ECG changes when stent-edge spasm was provoked after injection of ergonovine showed axis deviation to the left. This might indicate ischemia of the ventricular septum induced by vasospasm occurring in the first major septal branch.
This case is clinically important because it describes the potential hazard of stent-edge spasm after stent implantation. The patient’s clinical course provides the following two important clinical suggestions. First, that DES implantation for effort angina can induce new-onset stent-edge spasm, and second, stent-edge spasm may have an important role in the development of subacute ST.
The first clinical suggestion is that DES implantation for effort angina can induce new-onset stent-edge spasm. A recent study showed that endothelial dysfunction and enhanced vascular smooth muscle contractility with the involvement of the Rho-kinase pathway play an important role in the pathogenesis of DES-induced coronary vasospasm [1, 2]. Coronary vasoconstrictive responses are enhanced at the edges of coronary segments implanted with DES compared with BMS. The incidence of provoked spasm is not different between patients with and without VSA before stenting ; therefore, it is important to be concerned about the occurrence of new stent-edge spasm in patients both with and without VSA. It is possible that repeated, broad, strong, and long stent-edge spasm results in new cardiac events, and death was reported in some patients with severe multivessel, non-intervention-related vascular spasm after DES implantation [7, 8]; adjunctive medical treatment is critical for these patients. Long-term administration of vasodilating drugs, such as calcium channel blockers and nitrates are useful for inhibiting coronary vasospasm. Among four major calcium channel blockers (benidipine, amlodipine, nifedipine, diltiazem) that effectively suppress VSA, benidipine has shown significantly more beneficial prognostic effects .
The second clinical suggestion is that stent-edge spasm may have an important role in the development of subacute ST. There are two possible reasons for this phenomenon. The first is that coronary vasospasm promotes coagulation and may lead to thrombus formation. Some studies focused on the relationship between coronary vasospasm and thrombus formation have observed accelerated platelet and coagulation activities induced by coronary artery spasms [3, 10]. Platelet aggregation in the coronary circulation causes coronary thrombus formation, which may result in acute myocardial infarction . Several cases in which coronary vasospasm led to coronary thrombosis and myocardial infarction have also been reported [11, 12], supporting a potential mechanism underlying the phenomenon of the stent-edge spasm-related subacute ST in this patient. The second possible reason for the phenomenon of subacute ST secondary to stent-edge spasm is that this patient had few subacute ST risk factors except for the CYP2C19 polymorphism and the stent-edge spasm. CYP2C19 polymorphisms have been associated with weaker antiplatelet responses to clopidogrel, and nonresponsiveness to clopidogrel is an independent predictor of ST . However, CYP2C19 polymorphisms are frequent, especially in Japanese individuals, and the incidence is estimated about 20–25% of Japanese population . Therefore, multiple overlapping risk factors are required for the development of ST, even in patients that are poor metabolizers of clopidogrel. Several studies have evaluated the potential predictors of acute and subacute ST. Multiple risk factors related to devices, patients, lesions, and procedure have been suggested in the development of ST [15, 16]. Although this patient had a CYP2C19 polymorphism, he had no other significant risk factors for the development of subacute ST. Device-related factors (e.g., stent material and design) were not a problem. Regarding patient and lesion-related factors, this patient did not have acute coronary syndrome, old age, diabetes, or low left ventricular ejection fraction and the target lesion was non-complex with simple characteristics. Concerning procedure-related factors, the deployed stent had no morphometric (underexpansion or asymmetry) or morphologic (dissection, incomplete apposition, or tissue protrusion) abnormalities. Therefore, another mechanism beyond the above risk factors must have played a role in ST development in this case. It is possible that the patient’s platelet function was not adequately reduced despite the standard post-stent DAPT administration (100 mg/day aspirin and 75 mg/day clopidogrel) before PCI. In addition, the stent-edge spasm likely promoted the coagulation system and thrombus formation to increase the risk of ST.
Unfortunately, we lacked a baseline spasm provocation test before DES implantation and it is unknown whether coronary vasospasm was already present or not. However, the result of the fractional flow reserve evaluation showed myocardial ischemia and the patient’s symptoms also obviously changed from typical exertional chest pain to chest discomfort at rest after stenting. The clinical course indicated that his coronary vasomotor response was not clinically problematic before stenting, even if he already had coronary vasospasm. Therefore, we believe that coronary vasospasm became apparent after DES implantation and that stent-edge spasm should have been treated with antivasoconstrictive drugs to control and prevent the occurrence of subacute ST.
This case is clinically important because it describes the potential hazard of DES-induced coronary vasospasm, which may have caused subacute ST. Although various risk factors overlap to contribute to the development of ST, we believe stent-edge spasm also has an important role in ST development. Therefore, we should monitor new-onset rest angina after stent implantation and carefully assess DES-induced coronary vasospasm.
We would like to thank the staff of the Saiseikai Izuo Hospital. Furthermore, we are indebted to Editage, an editing company, for critical reading of the manuscript.
Availability of data and materials
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
HS collected, analyzed, and interpreted the patient data and drafted the manuscript. YA conceptualized the study and its objective, supervised the conduct of the study and also drafted the manuscript. YM and MY extracted the data and provided the clinical information. MK helped to interpret the data and draft the manuscript. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
Ethics approval and consent to participate
Standards of reporting
We adhered to CARE guidelines/methodology.
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