Amyloidosis as a cause of ischemic heart disease of small vessel origin.

In most patients, angina pectoris, acute myocardial infarction, and other manifestations of ischemic heart disease are related to atherosclerosis of the major, extramural coronary arteries (1). Clinical manifestations generally arise in the setting of significant stenosis (75% or more luminal narrowing) by atherosclerotic plaque and frequently with thrombotic occlusion, which is typically associated with plaque ulceration or rupture (1). However, clinically significant myocardial ischemia and infarction can result from several conditions in the absence of coronary atherosclerosis (2), including intramural small vessel disease, which can develop from hypertension, diabetes mellitus, or amyloidosis, and hematologic conditions (such as sickle cell disease or thrombotic thrombocytopenic purpura), or on an idiopathic basis (3). Nevertheless, symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis is not a well-documented or recognized entity. In this context, Mueller et al (4) have published convincing evidence in this issue of The Green Journal that obstructive intramural coronary amyloidosis can lead to symptomatic ischemic heart disease in the absence of significant extramural coronary amyloidosis, based on a review of 11 patients seen at the Mayo Clinic and an additional 11 patients reported in the literature. In the 11 cases studied by the authors, the diagnosis was made at autopsy or after examination of the explanted heart in those undergoing cardiac transplantation. All 11 patients in the current series, as well as the 11 previously reported patients, had angina pectoris. Other clinical manifestations included unstable coronary syndromes, heart failure, and electrocardiographic changes. Mueller et al (4) found that significant intramural coronary amyloidosis was a complication of primary systemic amyloidosis rather than senile cardiac amyloidosis. All of the patients in the series of Mueller et al had abnormal serum or urine protein electrophoresis with abnormal expression of a kappa or lambda light chain; in 9 of the 11 patients, an antemortem tissue diagnosis of systemic disease was made from biopsy specimens. Cardiac involvement in these patients had several features that distinguish it from clinically significant cardiac amyloidosis, which typically has extensive interstitial infiltration, with vascular involvement of variable extent and severity (5,6). The patients discussed in this issue of the Journal had extensive, intramural vascular involvement with a variable, less prominent interstitial component. This pattern may explain the surprising observation of low voltage in only 2 of the 11 patients. Low voltage in the standard limb leads is present in most cases of extensive cardiac involvement and is an important diagnostic feature of cardiac amyloidosis (5,6). Because of sampling problems and small amounts of tissue available for study, it is not surprising that endomyocardial biopsy was of marginal help in these patients. Endomyocardial biopsy was performed on 4 patients, and although amyloid was found in 3, none had biopsy evidence of intramural coronary amyloidosis. Mueller et al (4) document clinical correlates of the distinctive pattern of predominant intravascular cardiac amyloidosis. Cardiac involvement commonly develops in patients with primary systemic amyloidosis and often is fatal. The usual manifestations are heart failure, orthostatic hypotension, conduction system disease, and valvular heart disease. Mueller et al document that cardiac amyloidosis may also present as an ischemic syndrome with angina pectoris or myocardial infarction. The diagnosis of obstructive intramural coronary amyloidosis should be considered when obstructive epicardial coronary atherosclerosis is excluded and biopsy or laboratory evidence of systemic amyloidosis is obtained. Appropriate treatment of the cardiac ischemic syndrome should be considered within the context of management of the underlying systemic amyloidosis.