Letter by Morikawa et al Regarding Article, “Coronary Artery Spasm: A 2009 Update”
To the Editor:
Coronary artery spasm (CAS) is a rather common disease in East Asia, particularly Japan. However, it has been underappreciated and given little attention in Western countries. We thus welcome the appearance of the article “Coronary Artery Spasm: A 2009 Update” by Stern and de Luna in this journal.1 We are, however, disappointed to find that this article does not necessarily reflect the current status of this disorder.
Although an ECG showing transient ST elevation is highly specific for CAS, ST depression rather than elevation is more frequently associated with CAS.2,3 The episodes may not occur during ambulatory monitoring, and exercise testing may not be helpful because it is often negative in the daytime.2 Provocation testing with intravenous ergonovine should not be used because simultaneous multivessel spasm may occur, resulting in lethal arrhythmias, shock, or even death. CAS can be diagnosed accurately only by coronary angiography. Most cardiologists in Japan now use intracoronary injection of acetylcholine because this agent is extremely short-acting and most of the spasm disappears spontaneously within 1 to 2 minutes without nitroglycerin, thereby making it possible to examine both the right and left coronary arteries for possible multivessel spasm.2,3
The role of the autonomic nervous system in CAS is not established. CAS may occur after cardiac denervation or after autotransplantation or heterotransplantation.4 Endothelial dysfunction (deficient nitric oxide bioactivity and increased reactive oxygen species) with resulting increased proliferation and Ca sensitivity of smooth muscle cells is critical for the pathogenesis of CAS.2,3 CAS is a systemic disorder; entire coronary arterial trees or multivessels are often involved, although branch points are more susceptible probably because of oscillatory shear stress at these sites.2,3 Systemic risk factors include aging, smoking, chronic low-grade inflammation, and polymorphisms of genes related to nitric oxide and reactive oxygen species.2 Hypercholesterolemia is a negative risk factor for CAS; thus, CAS seems to be a distinct type of arteriosclerosis that is different from lipid-laden atherosclerosis.3
Calcium channel blockers are established therapy for CAS. Long-acting nitrates and nicorandil also are efficient through either the release of nitric oxide or the hyperpolarization of smooth muscle cells.2 These drugs should be given at night because CAS occurs most often from midnight to early morning. CAS recurs often on cessation of the drugs, and long-term control is necessary.2 However, it is not established how long the drugs should be administered. Recently, we have shown that a statin (fluvastatin) suppressed CAS probably through its pleiotropic effects, including improvement of endothelial dysfunction and suppression of calcium sensitivity through inhibition of the Rho-A/ROCK pathway.1 CAS is a medically treatable disorder, and there is no indication for coronary artery bypass graft surgery or percutaneous coronary intervention for relief of CAS itself. Medications should be continued in patients with CAS after percutaneous coronary intervention or coronary artery bypass graft surgery for organic stenosis because CAS may recur often even after these interventions.5 We do not recommend implantable cardioverter-defibrillators for CAS because arrhythmias, even life threatening, disappear with suppression of CAS. Smoking cessation is obligatory. Moderate exercise and relief from mental stress also are recommended.
Sources of Funding
Supported in part by grants from Japan Heart Foundation and Japan Vascular Disease Research Foundation, Japan.