Coronary artery vasospasm (CAVS) is a constriction of the coronary arteries that can cause complete or near-complete occlusion of the vessel. In 1959, Dr. Myron Prinzmetal described a different entity of angina than the classic Heberden's angina which was originally described in 1772. This vasospastic disease can cause acute ischemia and present anywhere along the spectrum of angina from stable angina to acute coronary syndrome. CAVS appears to be a heterogeneous disease but does not follow the traditional risk factors in the development of coronary artery disease.
The development of CAVS is multifactorial and can be influenced by the autonomic nervous system, inflammation, oxidative stress, endothelial dysfunction, smooth muscle cell hypercontractility, genetic predisposition, and lifestyle choices. Prinzmetal et al. published their study in 1959, which was conducted on 25 dogs where they noticed the changes that took place by occluding and releasing a large epicardial artery. They found clinical symptoms of pain and angina, electrocardiographic changes consistent with ischemia in the corresponding region, and systolic ballooning of the ischemic region. They postulated this as the course of a vasospastic epicardial coronary artery.
The prevalence of CAVS is highest between the ages of 40 and 70 and tends to decrease after 70 years. The distribution is varied throughout the world, with the highest incidence noted in Japanese population when compared to the western population. Furthermore, the frequency of multiple spasms noted on provocative testing is also higher in the Japanese population (23%) than those in Caucasians (7.5%). A German study found that every fourth patient with suspected obstructive coronary artery disease (CAD) had no culprit lesion, of these tested with acetylcholine, 50% were confirmed to be due to CAVS.
The pathogenesis of CAVS remains to be multifactorial. Originally the autonomic nervous system was thought to play an important role in the development of CAVS. However, later endothelial dysfunction, oxidative stress load, magnesium deficiency, and respiratory alkalosis were also elucidated to contribute to the pathogenesis. Most recently, genetic mutations have also been discovered which may play a role. Nevertheless, coronary vessels smooth muscle hypertonicity and reactivity play a pivotal role in the development of CAVS.
Increased inflammation has been associated with CAVS. Inflammation in CAVS histologically can present with infiltration of inflammatory cells such as mast cells. Mast cells have been reported at the site of CAVS, in the adventitia, and in the plaque of coronary arteries in patients with CAVS.
About 20 % to 30% of those complaining of chest pain who are evaluated for obstructive coronary artery disease with a coronary angiogram have normal coronary arteries. These patients may or may not present with symptoms. If symptoms are present, they may include typical anginal complaints during the episodes of vasospasm. CAVS induced pain can appear at rest and particularly between night and early morning and can be accompanied by low exercise tolerance, especially in the morning. A patient can describe this pain as crushing, substernal chest pain with features such as radiation to the jaw or arm, and pain relieved by sublingual nitroglycerin. The physical examination should consist of a thorough cardiovascular exam, beginning with noting the vitals and ensuring hemodynamic stability and then auscultating for the heart sounds. Physicians should pay attention to the rhythm, rate, murmurs, and extra heart sounds such as S3 or S4, as well as the pulmonary exam particularly paying attention to the development of crackles which could indicate pulmonary edema.
An electrocardiogram (ECG) should be recorded during the episode. Changes that can be seen are ST-elevation corresponding to the occlusion of the culprit lesion with ST depression in the contralateral leads. A diagnosis can be made if the patient is given a fast-acting nitrate during the episode and ECG findings resolve. In some cases, only ST depression can be seen in the contiguous leads. Other findings on ECG may include the development of negative T waves in the culprit lesion territory during recovery from ischemia and development of negative U waves during an active spasm.
Blood can also be checked for the release of cardiac biomarkers including Troponin I or C and creatinine kinase. However, these biomarkers are not always elevated in patients with CAVS induced chest pain.
Medical therapy with risk factor modification is the cornerstone of treatment and management of this patient population. Treatment initially consists of administering nitrates usually in the form of sublingual nitroglycerin. Nitrates cause relaxation of vascular muscle by activating the guanylate cyclase to increase the production of cGMP. CAVS should also be treated with calcium channel blockers that lower the calcium intake into the vascular smooth muscle.
Usually, CAVS can be relieved by vasodilatation. However, there are instances when the vasospastic disease is resistant to drug therapy including long-acting medications. This scenario is met in approximately 20% of the patients with CAVS. In these cases, percutaneous balloon angioplasty has not lead to favorable results. Percutaneous coronary intervention has also been studied with the continuation of medications as long-term. However, some of these patients return to vasospasm in another location. Thus, coronary stenting with long-term medical therapy should only be considered in patients who have significant stenosis from CAVS.
The application of implantable cardioverter defibrillators in patients with CAVS who present with ventricular tachycardia or ventricular fibrillation remains unknown. However, there have been reports of favorable outcomes in implanting the device in patients who survive fatal ventricular arrhythmias due to CAVS.
Due to the heterogeneous presentation of CAVS, it can initially be mistaken for multiple other cardiac pathologies. CAVS may or may not present with chest pain, ECG changes, and elevated cardiac biomarkers. Thus, obstructive atherosclerotic coronary artery disease, pericarditis or myopericarditis, primary arrhythmias, and stress-induced cardiomyopathy, should always be on the differential.
Coronary angiography with provocative testing is the only definite test that can confirm CAVS disease. Provoked CAVS is defined as luminal narrowing of 50%, 70%, 75%, or 90% with accompanying symptoms and/or ECG changes. This is then followed by intracoronary administration of nitroglycerin to dissipate the vasospastic changes on the vessel. Currently, in the United States, methylergonovine (a form of ergonovine) and acetylcholine are used in provocative testing that causes vasoconstriction in coronary arteries that have endothelial dysfunction.
Recurrent episodes of angina are usually seen in 4% to 19% of the patients. Advanced age and impaired left ventricular function have been identified as factors for poor prognosis in patients who present with acute coronary syndrome due to CAVS. In addition, elevated hs-CRP levels predict the higher risk of death, non-fatal myocardial infarction, and recurrent angina requiring repeat coronary angiography. However, the prognosis is usually favorable as long as the patients are maintained on calcium channel blockers and risk factors such as smoking are addressed.
Due to the heterogeneity of symptoms upon presentation, CAVS should be on a differential when a patient is presenting with symptoms. It is important to recognize CAVS when compared to obstructive atherosclerotic coronary artery disease due to different approaches to treatment. Furthermore, patients should be counseled to modify risk factors that can precipitate CAVS such as smoking, and treatment should be targeted in initiating and maintaining maximum tolerated doses of calcium channel blocker. Due to patients having recurrent symptoms resulting from CAVS further research needs to be implemented to understand the pathogenesis and impact treatment options better.