Abstract
Background
Coronary vasomotion disorders, although prevalent among patients with ischemia, remain poorly understood given limited use of invasive functional testing.
Case Summary
Presented here is a case of isolated severe right-coronary-artery vasospasm with acetylcholine reactivity testing resulting in ventricular arrhythmias.
Discussion
Determining the type of coronary vasomotion disorder is important for providing the appropriate treatment; therefore, performing invasive functional testing is critical. Although isolated right-coronary-artery vasospasm is rare, if vasospastic angina is of high suspicion, evaluating the right coronary artery is necessary.
Take-Home Messages
Vasospastic angina can occur in any phase of coronary atherosclerotic disease and result in myocardial infarction or sudden cardiac death. Vasomotor disorders can involve variable regions and combinations of microvascular and epicardial coronary arteries. A comprehensive diagnosis of vasomotor disorders is only possible with reactivity testing, with isolation of both right and left coronary arteries when indicated.
Key words: acetylcholine, microvascular, nonobstructive coronary artery disease, Prinzmetal, vasospasm, vasospastic
Visual Summary
Visual Summary.
Summary of the Patient's Hospitalization
History of Presentation
A 67-year-old male with known mild coronary artery disease (CAD) was instructed to present to the emergency department following ventricular tachycardia (VT) identified on his cardiac event monitor. The patient reported an episode while exiting his work truck the prior evening, endorsing substernal chest pressure with radiation to his neck and left arm, shortness of breath, and minimal palpitations. He self-administered sublingual nitroglycerin at the onset of his symptoms, with slow improvement, and returned to baseline in <5 minutes. Although completely asymptomatic on presentation, further review of the remote event monitor revealed sustained VT, precipitated by clear ST-segment elevations, as shown in Figure 1. Previous similar events have prompted visits to the emergency department, with his most recent visit being 1 month prior while drinking coffee with friends and discussing politics. The patient first became aware of these events approximately 5 years prior, with increasing frequency over the past 2 years. More recently, the episodes occurred monthly, all lasting minutes and nonexertional. However, he stated they are possibly related to psychological stress involving the recent passing of his brother.
Take-Home Messages
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•
Vasospastic angina can occur in any phase of coronary atherosclerotic disease and result in myocardial infarction or sudden cardiac death.
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Vasomotor disorders can involve variable regions and combinations of microvascular and epicardial coronary arteries.
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Comprehensive diagnosis of vasomotor disorders is only possible with reactivity testing, with isolation of both right and left coronary arteries when indicated.
Figure 1.
Cardiac Event Monitor
Rhythm strip from an ambulatory event monitor demonstrates ST-segment elevations that precipitate a sustained polymorphic ventricular tachycardia.
A recent transthoracic echocardiogram showed left ventricular ejection fraction of 68% with grade I diastolic dysfunction. The outpatient stress echocardiogram was normal after exercising 9 minutes and achieving 10.1 METs. Subsequent coronary computed tomography angiogram revealed only mild CAD and a mid-ascending aortic aneurysm measuring up to 4.9 cm. The patient had no known peripheral artery disease. The patient was diagnosed with nonobstructive CAD and treated with a statin, angiotensin II receptor inhibitor, beta-blocker, and sublingual nitroglycerin as needed. However, given recurrent symptoms, a cardiac monitor was placed only 3 days before this presentation.
Past Medical History
The patient had a non-ST-elevation myocardial infarction 15 years prior for which he underwent cardiac catheterization that demonstrated nonobstructive CAD and did not require an intervention.
Differential Diagnosis
Despite multiple outpatient studies negative for obstructive CAD, acute coronary syndrome, including unstable angina resulting from plaque disruption, was initially considered and ruled out. Nonischemic arrhythmia and related symptoms were ruled out on both outpatient remote monitoring and inpatient telemetry. In addition, it did not explain ischemic changes on electrocardiogram (ECG). In the setting of angina and ECG changes seen in Figure 1, the leading diagnosis was ischemia with no obstructive CAD (INOCA), which includes vasomotion disorders affecting epicardial and/or microvascular coronary arteries.
Investigations
Results of the medical examination performed in the emergency department are as follows: afebrile (36.5 °C), with blood pressure 136/70 mm Hg, pulse rate 87 beats/min, oxygen saturation 96% on room air, and high-sensitivity troponin 22 ng/dL and remained negative upon trending inpatient. His ECG revealed normal sinus rhythm without significant ST-segment changes as displayed in Figure 2.
Figure 2.
Baseline Electrocardiogram
The electrocardiogram on arrival revealed normal sinus rhythm without significant ST-segment changes.
Coronary angiogram demonstrated only mild CAD, as well as slow flow (>3 beats for complete opacification of the epicardial vessels), indicating potential microvascular disease. A quantitative assessment for microvascular disease was not performed as the technology was not accessible at the time. There were no definitive angiographic signs of plaque disruption although no intracoronary imaging was performed. Given the severity of the patient's anginal symptoms and ischemic findings, invasive coronary reactivity testing with acetylcholine challenge immediately followed as decided preprocedurally. The left main coronary artery was engaged with a Judkin Left 3.5-F guide catheter (Video 1). Infusion of acetylcholine was initiated at 0.082 μg/L and continued for 30 seconds, with a negative response. Acetylcholine concentration was increased to 0.82 μg/L, then to 8.2 μg/L, each for 30 seconds; however, a positive response involving anginal symptoms, visual coronary vasospasm, or flow reduction was not elicited (Video 2, Video 3, Video 4). Given high clinical suspicion and normal left coronary artery results, the decision was made to test the right coronary artery (RCA).
Following RCA engagement with a Judkin Right 4-F guide catheter (Video 5), acetylcholine infusion was initiated at the lowest concentration of 0.082 μg/L. The patient almost immediately reported symptoms of angina, stating, “Here it comes…I’m having an episode now,” at which point the acetylcholine was stopped. A repeat right coronary angiogram revealed diffuse vasospasm (Figure 3, Video 6). Therefore, a nitroglycerine intracoronary bolus of 200 mcg was administered, followed by an intravenous infusion of 100 mcg/mL/min. Telemetry displayed inferior ST-segment depressions, followed by brief pauses, and then sustained ventricular fibrillation (Figure 4), for which the patient required defibrillation twice before returning to sinus rhythm. Following approximately 5 minutes of nitroglycerine infusion, the patient remained hemodynamically stable, and a repeat RCA angiogram showed complete resolution of vasospasm; therefore, nitroglycerine infusion was discontinued (Video 7).
Figure 3.
Right Coronary Angiogram With Acetylcholine Reactivity Testing
(A) Invasive coronary angiography was performed in the left anterior oblique (LAO) view of the right coronary artery (RCA) prior to administration of acetylcholine demonstrating no significant stenosis. (B) After starting 0.082 μg/L of acetylcholine infusion, repeat coronary angiography in the LAO view demonstrates multifocal coronary vasospasm throughout the RCA. (C) An intracoronary bolus of 200-mcg nitroglycerin was administered, and the coronary vasospasm completely resolved.
Figure 4.
Intraprocedural Telemetry
(A) Telemetry during acetylcholine infusion demonstrated ST-segment depressions followed by brief pauses that precipitated sustained ventricular fibrillation, (B) requiring defibrillation.
Management
With a predominant diagnosis of vasospastic angina (VSA) affecting the RCA, long-acting nitrate was initiated, and the patient's beta blocker was discontinued and substituted with a calcium channel blocker. Given sustained VT on the remote monitor and intraprocedural sustained ventricular fibrillation requiring defibrillation, electrophysiology was consulted, and intracardiac defibrillator implantation was performed prior to discharge.
Outcome and Follow-Up
The patient remained asymptomatic on postdischarge follow-up. Cardiac rehabilitation was initiated for lifestyle modifications, including identifying and avoiding factors implicated in this condition.
Discussion
Coronary vasomotor disorders have been estimated as high as 4 in 5 patients diagnosed with INOCA.1,2 This disease has been shown in large retrospective studies to be more common in women and carries a worse prognosis when compared to both symptomatic and asymptomatic patients with normal coronary arteries.3,4 Symptoms are typically chronic, with VSA resulting from disease affecting epicardial coronary arteries, historically known as Prinzmetal angina. Whereas microvascular angina (MVA), previously known as Syndrome X, results primarily from prearterioles and arterioles.2 Diagnosis is made by defining coronary anatomy as normal or nonobstructive through computed tomography or invasive coronary angiogram. Myocardial ischemia, often transient, can then be identified with noninvasive imaging or ECG. However, distinguishing between VSA and MVA is accomplished only by invasive measurements.
Acetylcholine reactivity testing is used to visually identify epicardial disease and VSA, whereas Doppler flow measures during hyperemia with adenosine are used to calculate coronary flow reserve and identify microvascular disease and MVA. Practice guidelines recommend (Class IIa) both invasive measures for patients with nonobstructive angiograms and normal physiology but high suspicion.5,6 Standard protocols for the limited number of experienced centers focus on the left anterior artery alone, unless technically prohibitive, leaving a strong possibility for false negatives owing to the lack of RCA assessment. Peter Ong et al7 presented the largest series of acetylcholine reactivity testing on 847 consecutive INOCA patients. They found epicardial spasms in 283 (33.4%) patients, 43 of which occurred in the right and left coronary arteries, whereas only a single patient (0.11%) had isolated RCA spasms. Microvascular spasms occurred in 205 (24.2%), with no isolated RCA microvascular spasms occurring.7 In addition, studies have shown coronary spasm location to change over time with repeat testing.8 Despite the variability, this invasive procedure provides the only method for accurately distinguishing between MVA and VSA, which benefit from separate distinct treatments.
Conclusions
Coronary vasomotor disorders can be variable in regionality and severity. Therefore, diagnosis may require cautious yet thorough invasive measures of flow-limiting disease.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Acknowledgments
The authors thank the following personnel from Aurora Cardiovascular and Thoracic Services: Sarah Kennedy and Jennifer Pfaff for editorial preparation of the manuscript and Brian Schurrer for assistance with the figures.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
Pretreatment Left Coronary Angiogram
Right anterior oblique caudal view of the left coronary system prior to acetylcholine infusion.
Left Coronary Angiogram Low-Dose Acetylcholine
Right anterior oblique cranial view of the left coronary system after 0.082-μg/L acetylcholine infusion.
Left Coronary Angiogram Medium-Dose Acetylcholine
Right anterior oblique cranial view of the left coronary system after 0.82-μg/L acetylcholine infusion.
Left Coronary Angiogram High-Dose Acetylcholine
Right anterior oblique cranial view of the left coronary system after 8.2-μg/L acetylcholine infusion.
Right-Coronary-Artery Angiogram
Coronary angiogram in the left anterior oblique view of the right coronary artery prior to administration of acetylcholine.
Right-Coronary-Artery Vasospasm
Coronary angiogram in the left anterior oblique view of the right coronary artery (RCA) after starting 0.082 μg/L of acetylcholine infusion demonstrated multifocal coronary vasospasm throughout the RCA.
Post Treatment of Right Coronary Artery Vasospasm
Coronary angiogram in the left anterior oblique view of the right coronary artery after intracoronary bolus of 200-mcg nitroglycerin was administered, and the coronary vasospasm completely resolved.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Pretreatment Left Coronary Angiogram
Right anterior oblique caudal view of the left coronary system prior to acetylcholine infusion.
Left Coronary Angiogram Low-Dose Acetylcholine
Right anterior oblique cranial view of the left coronary system after 0.082-μg/L acetylcholine infusion.
Left Coronary Angiogram Medium-Dose Acetylcholine
Right anterior oblique cranial view of the left coronary system after 0.82-μg/L acetylcholine infusion.
Left Coronary Angiogram High-Dose Acetylcholine
Right anterior oblique cranial view of the left coronary system after 8.2-μg/L acetylcholine infusion.
Right-Coronary-Artery Angiogram
Coronary angiogram in the left anterior oblique view of the right coronary artery prior to administration of acetylcholine.
Right-Coronary-Artery Vasospasm
Coronary angiogram in the left anterior oblique view of the right coronary artery (RCA) after starting 0.082 μg/L of acetylcholine infusion demonstrated multifocal coronary vasospasm throughout the RCA.
Post Treatment of Right Coronary Artery Vasospasm
Coronary angiogram in the left anterior oblique view of the right coronary artery after intracoronary bolus of 200-mcg nitroglycerin was administered, and the coronary vasospasm completely resolved.