Ms. M, a 52-year-old nonsmoker with no cardiac history, was diagnosed with Hodgkin lymphoma and was treated with chemotherapy followed by a stem cell transplant. After a period of remission, her lymphoma recurred, and she was readmitted to an oncology unit for a second stem cell transplant. Ms. M's inpatient posttransplant course was largely uneventful until 5 days later when she started to complain of crushing, substernal, nonradiating chest pain and associated shortness of breath. An ECG done at the time showed normal sinus rhythm with unremarkable findings compared with the baseline ECG. Ms. M's chest pain was attributed to gastric acid reflux, and she was given an antacid for symptom relief.

An hour later, Ms. M reported worsening chest pain at rest accompanied by shortness of breath and an episode of transient unresponsiveness witnessed by her husband. The RN activated the hospital rapid response team. Ms. M was responding appropriately and complained of persistent chest pressure rated at 7/10 (on a scale of 0 to 10) upon the team's arrival. A 12-lead ECG was done and showed third-degree atrioventricular (AV) heart block with a rate of 57 beats/minute; her respiratory rate was 22 breaths/minute; BP 85/49; she was afebrile, and her oxygen saturation was 92% on room air. Transcutaneous pacing pads were applied, and Ms. M was maintained on 2 L/minute nasal cannula oxygen (her vital signs improved and no medications were given since none were indicated at the time). Serial ECGs were done, and a cardiology consult was requested.

A subsequent ECG revealed normal sinus rhythm, with a heart rate of 74 and ST-segment depression (approximately 2 mm) in leads I and aVL. A succeeding ECG revealed deepened ST-segment depression in leads I, aVL, and V2 along with ST-segment elevation in the inferior leads. An ST-segment elevation myocardial infarction (STEMI) alert was activated, and Ms. M was given aspirin 325 mg orally, clopidogrel 300 mg orally, morphine 4 mg I.V. for pain, 1 L of I.V. crystalloid (0.9% sodium chloride) infusion was started for hypotension, and a heparin infusion was initiated. Ms. M was transferred to a cardiac catheterization center for cardiac catheterization and further management.

Ms. M's initial troponin level was negative. Her left heart catheterization showed a 20% stenosis of the right coronary artery and a 20% stenosis of the left anterior descending artery. However, during the left ventricular scan, she became hypotensive, and her ECG exhibited a third-degree AV block and inferior wall ischemia.

Ms. M was recatheterized, which showed 80% to 90% occlusion of the right coronary artery. She was given intra-arterial nitroglycerin after which symptoms significantly improved. Ms. M's symptoms, along with ECG and catheterization findings, were consistent with vasospastic angina, previously known as Prinzmetal angina.

Pathophysiology: Prinzmetal angina

Prinzmetal angina was first described in the 1950s and was thought to be a distinct type of angina pectoris because it typically presents during rest and is not associated with exertion.1 Prinzmetal angina is now known as vasospastic angina; previous terminology included variant angina, Prinzmetal's variant angina, angina inversa, and coronary spastic angina.

The cause was attributed to the temporary occlusion of coronary vessels due to increased vascular tone. Subsequent studies confirmed that the mechanism of this disease is due to coronary vasospasms.2 This process is different from the occlusive changes caused by atherosclerotic coronary artery disease. The phenomenon occurs in approximately 2% to 10% of patients in the general population.3

Although the exact pathogenesis of this condition is still being debated, it is believed that endothelial dysfunction, inappropriate nitric oxide release, and calcium channel disorders are potential causes.2 A typical symptom is retro-sternal chest pain that occurs at rest. In addition, there appears to be a circadian pattern, with patients typically experiencing chest pain early in the morning. ECG changes may show transient ST-segment elevations in severe cases.4

Troponin (normal range is less than 0.04 ng/mL) is usually negative, and coronary catheterization often shows nonocclusive coronary arteries with vasospasm.4 Traditionally, patients are treated with nitroglycerin and calcium channel blockers with great success.4 Complications of vasospastic angina can include dysrhythmia, AV block, and even cardiac arrest.5-9

This case was unique in that Ms. M had no smoking history, and her symptoms mimicked an inferior wall myocardial infarction (MI) with a high-degree AV block due to her vasospasm vessel distribution. ST-segment depression (or T-wave inversion in lead aVL) could be early reciprocal changes that precede an inferior wall MI.10 The clinician should obtain serial ECGs when this finding is noted.10

Current best practices

Previously, there were no established guidelines in North America or Europe for vasospastic angina diagnosis and treatment. This is attributed to its decreasing incidence (primarily due to the widespread availability and use of calcium channel blockers in the treatment of hypertension and other cardiovascular conditions).11 However, in 2015, the Coronary Vasomotion Disorders International Study Group published a definitive criteria in diagnosing vasospastic angina.

The criteria indicates that the diagnosis can be made if resting angina is relieved by nitrates, especially if angina occurs in the morning, can be brought on by hyperventilation, or the episode can be reduced via calcium channel blockers; or if over 90% stenosis of the coronary artery is noted during angiography during a vasopastic episode that is either spontaneous or provoked.12

In addition, characteristic ECG changes during angina episodes include transient ST-segment elevation of 0.1 mV or more; an ST-segment depression of 0.1 mV or more; or the new appearance of negative U waves (recorded in at least two contiguous leads on the 12-lead ECG).12 Calcium channel blockers are traditionally used in vasospastic angina due to their effect on L-type calcium channels in coronary vessels. The vessel spasms cause transient mechanical occlusion when calcium channels are stimulated. With a calcium channel blocker, its therapeutic effect relies on its ability to suppress vessel spasms.13

A Japanese meta-analysis examined specific types of calcium channel blockers and the efficacy of each. It was shown that benidipine (not FDA-approved for use in the United States) had higher efficacy in controlling coronary vasospasm than other calcium channel blockers, such as amlodipine, diltiazem, and nifedipine. This phenomenon is attributed to benidipine's higher affinity for coronary smooth muscles along with having a longer half-life regardless of blood concentration.11

Acute management consists of rapid-acting nitrates for chest pain relief and a calcium channel blocker, alone or in combination with a long-acting nitrate, to reduce occurrence. In addition, an HMG-CoA reductase inhibitor, cessation of tobacco use, and other lifestyle changes that can reduce the risk for atherosclerotic disease should be instituted.13

Small studies have shown that coronary stenting may be a viable and safe option that provides symptomatic relief for patients who have severe symptoms and are refractory to medical treatments.14

Implications for practice

Traditionally, vasopastic angina is associated with smoking, magnesium deficiency, a high level of C-reactive protein, cold weather, cocaine use, and stress.2,13 Smoking cessation is key to preventing recurrence of symptoms, as smoking is strongly correlated with vasospastic angina.2 Smoking is a significant risk factor in vasospastic angina and needs to be addressed in the overall management; it warrants special consideration in the prevention and recurrence of vasospastic angina.11-13

The last decade has seen the strongest advocacy for smoking cessation (in the media) regarding public gathering places and in health policy discussions. NPs now have access to an array of pharmacologic products to help smokers quit.

The evidence strongly recommends for all clinicians to routinely ask all patients about smoking scenarios and to advise those who smoke about the importance of smoking cessation.15 NPs play a role in advising patients to quit smoking, and it has been shown to be effective.16 It is hoped that smoking cessation will become an integral conversation in every patient-clinician encounter in every healthcare system.

The case presented here was unique in that Ms. M had no smoking history. Her symptoms mimicked an inferior wall MI with high-degree AV block due to her vasospasm vessel distribution. This case highlights the importance of serial ECGs, and if possible, telemetry monitoring of the patient. The transient nature of vasospastic angina makes it elusive to a one-time, 12-lead ECG. It is important for NPs to hold a degree of suspicion and obtain serial ECGs if the patient remains symptomatic.

NPs should note the timing of angina during the health history interview; an ambulatory electrocardiography device may be ordered to aid in a definitive diagnosis if the patient has symptoms suggestive of vasospastic angina.4 NPs can provide high-quality patient education using the teach-back method for patients undergoing cardiac catheterization. The patient and his or her caregivers should be encouraged to ask questions and be referred to reputable online sources, such as the American Heart Association.17

Patient education related to vasospastic angina includes instructions related to taking calcium channel blockers and nitrates. Patients are reminded not to take calcium channel blockers with grapefruit juice due to latter's potential to reduce presystemic drug clearance and subsequent bioavailability increase, which could lead to hypotension.18

Patients are reminded to remain well hydrated and to get up slowly from recumbent or sitting positions to reduce the risk of orthostatic hypotension. Headache is one of the most common adverse reactions of nitrates, and patients need to collaborate with their providers on how best to manage this potential adverse reaction.

Follow-up and transition

Ms. M stayed in the cardiac care unit briefly for observation and was eventually readmitted to her primary facility where she continued lymphoma treatment. She was eventually discharged home and was prescribed a calcium channel blocker and nitroglycerin along with an outpatient follow-up with a cardiologist.

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