Coronary artery myointimal dysplasia in patients with pheochromocytoma-possible causal relationship: pathophysiology and clinical implication with reference to Takotsubo cardiomyopathy and spontaneous coronary dissection.

Myocardial damage in catecholamine cardiomyopathy, characterized by patchy myocyte necrosis commonly with contraction band appearances, interstitial fibrosis, and varying degrees of inflammatory infiltrates, has been well documented. However, coronary vascular pathology has not been recognized. Autopsy of a 43-year-old housewife who died of acute apical anteroseptal myocardial infarction revealed the incidental finding of a left adrenal pheochromocytoma. The epicardial and intramyocardial median- and small-sized coronary arteries exhibited myointimal dysplasia in the form of fibroblastic proliferation in the intima and media, resulting in thickened dysplastic vessels with marked luminal narrowing, occasionally leading to near-total occlusion. The distal left anterior descending artery showed features of recanalization after prior embolic occlusion. The density and severity of vascular involvement revealed a decreasing gradient from apical to basal region, mainly affecting the left ventricle, but the proximal coronary arteries were minimally affected. Myointimal dysplasia was not seen in control cases of hypertensive heart, and despite its presence in hearts with hypertrophic cardiomyopathy, it lacked the distinctive pattern of distribution and the epicardial vessels are uninvolved. Myointimal dysplasia probably results from reactive fibroplasia in response to the vasoconstrictive effect of circulating or local neurosecretory catecholamine and appears crucial in the pathogenesis of various types of catecholamine cardiomyopathy, including Takotsubo or stress cardiomyopathy. Together with the direct catecholamine cardiotoxicity, they result in diffuse microscopic ischemic necrosis and fibrosis. Depending on the type of catecholamine overproduction and action, together with the characteristic anatomic distribution and density of the various types of adrenergic receptors in the ventricles, different regions of the heart are variously affected so that different patterns of ventricular dysfunction are produced, with the subsequent angiographic appearances ranging from apical through midventricular to basal ballooning. Additional complications from the myointimal dysplasia include spontaneous coronary dissection, acute myocardial infarction, and superimposed thrombus formation in the dysplastic vessels and dyskinetic ventricle, with the risk of further damage from embolic events.