Abstract
The mechanisms responsible for persistent and lethal coronary spasm remain incompletely understood. Our group treated a patient with non-ST-elevation myocardial infarction (MI) caused by a spontaneously persistent spasm associated with high-grade macrophage accumulation. A 48-year-old man was transferred to an emergency room because of persisted chest tightness. The patient’s chest pain subsided without ST elevation when he arrived at the hospital, but he tested positive for fatty acid-binding protein. Emergent coronary angiography revealed a subtotal occlusion in the middle of the right coronary artery. The occluded lesion was released immediately after an injection of isosorbide dinitrate. No disruption, ulceration or erosion was observed at the culprit lesion segment on optical coherence tomography. The only finding was high-grade macrophage accumulation in the segment of the persistent focal coronary spasm. The present case suggests that the early stage of atherosclerosis with high-grade macrophage accumulation was associated with persistent coronary spasm resulting in acute MI.
Keywords: ischaemic heart disease, clinical diagnostic tests
Background
Coronary spasm only occasionally causes acute myocardial infarction (MI).1 The mechanisms responsible for persistent and lethal coronary spasm remain incompletely understood.2 Our team treated a patient with non-ST-elevation MI caused by a spontaneously persistent spasm associated with high-grade macrophage accumulation. To the best of our knowledge, there have been no earlier case reports describing marked accumulation of macrophages which played a role in the pathogenesis of focal coronary spasm. We therefore report the details of the case and discuss the clinical implications.
Case presentation
A 48-year-old man with a history of hypertension and smoking (20 cigarettes per day from 20 years old) was transferred to an emergency room because of chest tightness that persisted for more than 1 hour. The blood pressure was 165/113 mmHg. The patient’s chest pain subsided without ST elevation when he arrived at the hospital. However, the patient tested positive for fatty acid-binding protein. Transthoracic echocardiography showed severe hypokinesis in the inferior wall. Emergent coronary angiography revealed a subtotal occlusion in the middle of the right coronary artery (figure 1A). On angiography, the left coronary artery was normal. The occluded lesion was released immediately (figure 1B) after an injection of 2 mg of isosorbide dinitrate into the right coronary artery. The patient was diagnosed with non-ST-elevation MI caused by a persistent focal coronary spasm in the middle of the right coronary artery. No disruption, ulceration, erosion or significant irregularity was observed at the culprit lesion segment on optical coherence tomography (OCT; figure 2a–c, video 1). The only finding was high-grade macrophage accumulation in the segment of the persistent focal coronary spasm (figure 2B1, B2).
Figure 1.
Emergent coronary angiography revealed a subtotal occlusion in the middle of the right coronary artery (A). The occluded lesion was released immediately after an injection of isosorbide dinitrate (B).
Figure 2.
(a)–(c) Optical coherence tomography showed high-grade macrophage accumulation only in the segment of the persistent focal coronary spasm. No disruption, ulceration, irregularity or erosion was observed at the culprit lesion segment. (B1, B2) Considerable macrophage accumulation (arrows) was observed in the segment of the persistent focal coronary spasm with early-stage coronary atherosclerosis.
Video 1.
Outcome and follow-up
Peak creatine kinase myocardial band (CK-MB) was 10.2 ng/mL and troponin I was 2423 pg/mL. He was discharged without any cardiac events and complications. In the 18 months since the coronary event, the patient has remained stable under medication with a nifedipine (40 mg) and aspirin (100 mg).
Discussion
The prevalence of acute MI with non-obstructive coronary arteries (MINOCA) ranges between 5% and 25% of all MI.3 The prognosis of MINOCA may be worse than that of patients with non-ST-segment elevation MI with obstructive coronary artery disease, as reported in a retrospective analysis from the acute catheterization and urgent intervention triage strategy (ACUITY) trial.4 Coronary spasm is one of the common causes of MINOCA. In particular, in a recent study, provocative tests were positive in 46% of patients with MINOCA.5 Even though coronary spasm is generally diagnosed on angiography with a provocation test, the present case had spontaneous persistent coronary spasm and was diagnosed on emergent angiography. To the best of our knowledge, there are few reports that have assessed the morphology of coronary artery spasm segment with OCT. Shin et al studied 80 spasm sites of 69 consecutive patients who had vasospastic angina and underwent OCT imaging.2 The study showed that the main morphological characteristics of vasospastic angina were erosion and lumen irregularity as seen on OCT; three patients had fibrous cap disruption. The present case, however, did not have such morphological findings. Although our case had mild plaque at the persistent coronary spasm site, the lumen adjacent to the plaque was smooth and there was no thrombus. High-grade macrophage accumulation was the only OCT finding in the segment of the persistent focal coronary spasm. To the best of our knowledge, there are no studies that have investigated the association between macrophage accumulation and coronary spasm.
Macrophages are seen as signal-rich, distinct or confluent punctate regions that exceed the intensity of background speckle noise on OCT (medium evidence level).6 Macrophage accumulation observed in OCT have some possibility of artefact or misdiagnosis such as necrotic core, microcalcifications, cholesterol crystals or internal or external elastic membrane. In the present case, macrophage accumulations appear as confluent punctate highly backscattering focal regions within the artery wall. Those findings completely meet the definition of macrophage accumulation in OCT (figure 2a–c, video 1).6 Furthermore, visualising the images using an inverse grey scale confirmed macrophage accumulations and distinguished from the artefact or the other misdiagnosis (figure 2B2).
Patients with vasospastic angina have a pathophysiological phenomenon of vascular smooth muscle hyper-reactivity leading to spasm. Different pathogenic mechanisms such as endothelial dysfunction, inflammation and altered autonomic nervous system response, and genetic factors have been proposed as the underlying cause.7 The mechanisms responsible for persistent or lethal coronary spasm are not fully understood. The present case had a history of smoking and untreated hypertension. Those factors were probably associated with endothelial dysfunction and early stage of atherosclerosis. Rapid progression of atherosclerosis with high-grade macrophages accumulation might cause local inflammation resulting in persistent coronary spasm. The incidence of coronary spasm might be also modified by genetic factors in patients with early stage of atherosclerosis.
It is challenging to demonstrate the causative relationship between the macrophage accumulation and coronary vasospasm in a single clinical case. However, the present case suggested that the local inflammation with high-grade macrophage accumulation was associated with the incidence of lethal coronary spasm. Further case series and systematic studies are needed to determine the relationship between macrophage accumulation and coronary vasospasm.
In conclusion, the present case is important in that it suggests that the early stage of coronary atherosclerosis with high-grade macrophage accumulation was associated with persistent coronary spasm, resulting in acute MI.
Learning points.
The mechanisms responsible for persistent and lethal coronary spasm remain incompletely understood.
High-grade macrophage accumulation was the only optical coherence tomography finding in the segment of the persistent focal coronary spasm.
The present case suggests that the local inflammation with high-grade macrophage accumulation may be associated with the incidence of lethal coronary spasm.
Further case series and systematic studies are needed to determine the relationship between macrophage accumulation and coronary vasospasm.
Footnotes
Contributors: KW drafted and edited the manuscript. TN, TS and KT edited and reviewed the manuscript.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient consent for publication: Obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
References
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