Prinzmetal’s angina

ECG 1A: Sinus rhythm, normal PR interval; major elevation exceeding 10 mm in inferior leads, beginning at the peak of the R wave, encompassing the T-wave and constituting a monophasic dome-shaped wave; reciprocal depression in leads I, aVL, V3-V5; ventricular extrasystole followed by ventricular couplet;

ECG 1B: Tracing recorded a few minutes after the administration of 2 puffs of sublingual nitroglycerine which led to the resolution of chest pain; the modifications in the ST-segment disappeared; the amplitude of the R wave in the inferior leads is lower on this tracing than in the first tracing (increase of the R wave during the crisis);

Comments: This patient presents a Prinzmetal’s angina with spasm of the right coronary artery. The electrocardiogram and clinical presentation are characteristic: high transient elevation spontaneously ceasing or after administration of sublingual nitroglycerine. Coronary angiography showed a non-significant stenosis of the right coronary artery. Treatment with calcium channel blockers prevented recurrence of chest pain.

In 1959, Myron Prinzmetal described a particular form of angina, occurring preferentially at rest, at night or early in the morning, without the usual triggers of angina (exertion, stress, etc.) with evidence of a ST-segment elevation on ECG. The thoracic pain is typical, recurrent, spontaneously resolved and caused by spasm of one of the coronary arteries usually occurring in the presence of various triggering factors: cocaine use, marijuana or amphetamines, alcoholism (controversy on the subject), smoking, hyperventilation, hypomagnesemia, etc. Vasospastic angina affects relatively young women without cardiovascular risk factors, except for active or passive exposure to tobacco. Asthma, Raynaud’s syndrome or migraines are sometimes also documented. The incidence of coronary spasm nowadays appears to be decreasing because of treatments to reduce recurrences, the use of calcium channel blockers in hypertension and coronary artery disease, and the reduction in tobacco use.

The pathophysiology explaining the hyperactivity of the coronary smooth muscle cells is still poorly defined although many mechanisms are likely involved: genetic factors (increased incidence in Asia, less in Europe), oxidative stress, inflammation, etc. The endothelium participates in the regulation of vascular tone and probably plays a central role in the onset of spasm. Widespread or localized endothelial dysfunction is accompanied by changes in the release of nitric oxide, thus increasing the vasoconstrictive potential within the vessel. Although there is a transient transmural ischemia, the occurrence of an infarction is rare due to local self-regulatory mechanisms resulting in compensatory vasodilation. The risk of myocardial necrosis is nonetheless not zero, with at times massive myocardial infarction. Although mortality is low, Prinzmetal’s angina may also be complicated by syncope or sudden death due to ventricular arrhythmia or conduction disorder.

Since treatment differs significantly from that of an acute coronary syndrome due to thrombosis, the objectification of a spasm is an indispensable step in its management. The demonstration of a transient elevation is evocative of the diagnosis but difficult to obtain, the electrocardiogram usually normalizing within a few minutes.

In a majority of patients, coronary angiography does not reveal any significant lesion even though the presence of <50% stenosis is relatively frequent. During coronary angiography, a pharmacodynamic test with injection of a spasm-promoting agent (acetylcholine or methylergometrine) can be used for diagnosis. The methergin test (methylergometrine, a derivative of rye ergot) is most often used in clinical practice because simple to perform, inexpensive, with good sensitivity and specificity. The test is considered positive if the caliber of an artery is reduced by at least 70%.

Factors contributing to the occurrence of a spasm should be avoided, especially tobacco. Similarly, non-selective beta-blockers may promote vasoconstriction and are contraindicated in this setting. The management of patients with Prinzmetal’s angina has changed dramatically since the introduction of calcium channel blockers which represent the treatment of reference. A long-acting calcium channel blocker is proposed as a first-line solution with an optimized dosage to avoid undesirable side effects while controlling the occurrence of seizures with an overnight intake when symptoms are most frequent. The combination of two calcium channel blockers can be proposed in refractory patients. Other drugs such as long-acting nitrates, nicorandil, certain antioxidants and fluvastatin may also have a favorable effect on the prevention of seizures. Sublingual nitroglycerine helps to relax the spasm when it occurs.

When a patient remains symptomatic in spite of well-monitored maximal medical treatment, angioplasty with stent placement on a non-hemodynamically significant stenosis could reduce the occurrence of seizures even if study results are conflicting.

The risk of sudden death and the indication for an ICD in this setting will be discussed in one of the subsequent tracings.

Take-home message: Chest pain typical of Prinzmetal’s angina is recurrent, self-limiting, preferentially occurring at night or early in the morning and may be favored by a specific triggering factor (tobacco, cocaine use, cold environment, etc). The electrocardiogram during pain (when it can be recorded) shows a transient ST-segment elevation.