Letter by Tsigkas et al Regarding Article, “Coronary Artery Spasm: A 2009 Update”
To the Editor:
We read the interesting article published in your journal about updated pathophysiological mechanisms resulting in coronary arteries spasm (CAS). CAS poses a therapeutic challenge for the physician, considering the wide variety of responsible causal factors.1 We believe that new knowledge about mechanisms resulting in artery spasm has to be reported. Histamine or leukotrienes acting on coronary vascular smooth muscle were suggested by Braunwald2 to be vasospastic angina inducers. Kounis and Zavras,3 when first describing the “syndrome of allergic angina,” associated classic angina pectoris and increased inflammatory mediators with coincidental chest pain and allergic reactions. Kounis syndrome has 2 variants. In type 1, the acute allergic insult induces CAS with normal or abnormal cardiac enzymes and troponin in patients with normal coronary arteries and no predisposing factors. In type 2, the acute allergic episode can induce plaque erosion or rupture manifesting as an acute myocardial infarction in patients with atheromatous disease.
It is known that in anaphylactic degranulation several vasoconstricting and collagen-degrading compounds are released locally and peripherally such as histamine, neutral proteases (tryptase, chymase), platelet-activating factor, and de novo formed mediators (cytokines and chemokines) by the metabolism of arachidonic acid through activation of a phospholipase. The mediators include leukotrienes by the lipoxygenase pathway and prostaglandins such as thromboxane by the cyclooxygenase pathway. These mediators have been incriminated in clinical and experimental studies to induce CAS and/or acute myocardial infarction. Moreover, during experimental anaphylaxis, platelet-activating factor reproduces the mechanical and electric changes observed during allergic reactions such as ischemic ST-segment changes and arrhythmias. Platelet-activating factor acts through the release of leukotrienes and thromboxane or directly by producing vasoconstriction. Furthermore, cardiac mast cell–derived histamine can constrict the coronary arteries and sensitize nerve endings close to adventitial mast cells in atherosclerotic coronary arteries. Apart from being a powerful coronary vasoconstrictor, histamine can activate platelets and potentiate the aggregatory response of other agonists, including adrenaline, 5-hydroxytryptamine, and thrombin. Finally, eosinophils, responding to histamine-changed cell shape, upregulate adhesion molecules and chemotaxis thus associated with CAS. This cascade is the cornerstone of the hypersensitivity coronary syndrome known as Kounis syndrome.
Life-threatening allergic reactions with circulatory compromise occur at an annual rate of 7.9 to 9.1 per 100 000 population, with 10%, 18%, and 59% due to food, drugs, and venoms, respectively. Ischemic heart disease patients with possible hypersensitivity must undergo diagnostic procedures, including skin and antibody testing. Cases of Kounis syndrome are encountered more often in clinical practice than expected, and we believe that many more causative factors will be incriminated in the future.4 Patients with a history of systemic allergic reactions could selectively be evaluated for myocardial injury markers such as cardiac enzymes and troponins, together with histamine and tryptase levels. Although allergic episodes are common in everyday practice, few patients develop chest pain or ECG changes during these episodes. We believe that there is a threshold level of mast cell content activation (histamine, tryptase, chymase, leukotriene, thromboxane, platelet-activating factor, and chemokines) that could provoke CAS and/or plaque erosion or rupture.