A 34-year-old woman is brought to the emergency department due to chest pain. The patient reports that she went to bed feeling well and woke up in the middle of the night with severe, crushing chest pain that radiated to her left arm. She has had similar episodes over the past year that typically occur in early morning and spontaneously resolve after several minutes. The patient has a history of occasional migraine that responds to acetaminophen. She does not use tobacco, alcohol, or illicit drugs. Blood pressure is 150/100 mm Hg, pulse is 110/min, and respirations are 14/min. On physical examination, the patient appears distressed and is diaphoretic. ECG reveals ST-segment elevations in leads I, aVL, and V4-V6. The patient is given nitroglycerin, which improves her symptoms. Percutaneous coronary angiography is performed, and no obstructive lesions are observed. Which of the following is most likely to be involved in the pathogenesis of this patient's chest pain?
Vasospastic angina | |
Pathogenesis |
|
Clinical presentation |
|
Diagnosis |
|
CAD = coronary artery disease. | |
This patient most likely has vasospastic angina (formerly Prinzmetal angina), which involves intermittent coronary artery vasospasm leading to myocardial ischemia. The condition likely results from hyperreactivity of arterial smooth muscle due to a combination of endothelial dysfunction and autonomic imbalance.
The major underlying defect in vasospastic angina is likely a deficiency of vasodilatory nitric oxide in the coronary artery endothelium, causing acetylcholine released from vagus nerve terminals to trigger vasoconstriction rather than vasodilation. Patients typically experience episodes of recurrent chest discomfort that spontaneously resolve within 15 minutes. The episodes often occur at rest or during sleep, when vagal tone is at a peak. As with typical angina, there may be associated diaphoresis, nausea, and dyspnea, but unlike typical angina, patients are usually young (age <50) and lack most risk factors for atherosclerotic coronary artery disease (CAD) (eg, hypertension, diabetes). However, smoking is a strong risk factor, likely due to its contribution to endothelial dysfunction.
Vasospastic angina is usually diagnosed by ambulatory ECG (Holter monitor) that shows ST elevation during an episode of chest discomfort, followed by coronary angiography to rule out atherosclerotic CAD. Sublingual nitroglycerin is effective in relieving an active episode of vasospastic angina, and calcium channel blockers (eg, diltiazem, amlodipine) are effective in preventing episodes.
(Choices A and D) Endothelin-1 is a potent vasoconstrictor and prostacyclin is a vasodilator. Therefore, decreased expression of endothelin-1 or increased expression of prostacyclin would stimulate coronary vasodilation rather than vasospasm.
(Choice B) Granulomatous inflammation of arterial media occurs in Takayasu arteritis, a large-vessel vasculitis affecting the aorta and its major branches. Young women of Asian descent are most commonly affected and sometimes develop angina due to coronary artery involvement; however, limb claudication (due to subclavian artery involvement) accompanied by constitutional symptoms (eg, fever, fatigue) is a more common presentation.
(Choice E) Ulceration of the thin fibrous cap overlying an atherosclerotic plaque can lead to unstable angina, characterized by intermittent chest discomfort similar to that of vasospastic angina. However, atherosclerotic CAD is unlikely in this young woman without significant CAD risk factors.
Educational objective:
Vasospastic angina involves hyperreactivity of coronary artery smooth muscle. Patients are usually young (age <50) and without significant risk factors for coronary artery disease; they experience recurrent episodes of chest discomfort that typically occur during rest or sleep and resolve within 15 minutes.