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Original Articles

Angina in Fabry Disease Reflects Coronary Small Vessel Disease

Cristina Chimenti, MD, PhD; Emanuela Morgante, PhD; Gaetano Tanzilli, MD; Enrico Mangieri, MD; Giuseppe Critelli, MD; Carlo Gaudio, MD; Matteo A. Russo, MD and Andrea Frustaci, MD

From the Heart and Great Vessels "Attilio Reale" Department (C.C., G.T., E.M., G.C., C.G., A.F.) and Pathology and Experimental Medicine Department (E.M., M.A.R.), La Sapienza University, Rome, Italy; Molecular and Cellular Cardiology Laboratory, National Institute for Infectious Disease "L. Spallanzani" (C.C., A.F.), Rome, Italy; and IRCCS San Raffaele La Pisana (C.C., M.A.R.), Rome, Italy.

Correspondence to Andrea Frustaci, MD, Heart and Great Vessels "Attilio Reale" Department, La Sapienza University, viale del Policlinico 155, 00100 Rome, Italy. E-mail: biocard{at}inmi.it

Received May 5, 2007; accepted July 23, 2008.

Background— Chest pain is frequently reported in Fabry disease (FD). However, its mechanism and clinical relevance are unclear.

Methods and Results— Basal troponin I level, exercise stress test, single-photon emission computed tomography imaging with ^99mTc sestamibi, coronary angiography with thrombolysis in myocardial infarction (TIMI) frame count and left ventricular angiography and endomyocardial biopsy were obtained in 13 patients with FD with angina. Ratio of external to lumen diameter of intramural arteries (E/L ratio), myocyte diameter, and extent of fibrosis were morphometrically evaluated by using tissue sections. Controls for coronary angiography and histology were 25 patients with FD without angina and 20 mitral stenosis patients with normal left ventricular function. Troponin I level was elevated in 6 of the 13 patients. Exercise stress test showed evidence of myocardial ischemia, and single-photon emission computed tomography was positive for stress-induced perfusion defects in all patients with FD with angina. Epicardial coronaries were structurally normal but showed slow flow in all and were associated with aneurisms of posterior left ventricular wall in 3 cases. Histology showed remarkable lumen narrowing of most intramural arteries (mean E/L ratio=3.5±1.2; P<0.001 versus both control groups), because of hypertrophy and proliferation of smooth muscle and endothelial cells, both engulfed by glycosphingolipids. Replacement fibrosis exceeded that of both controls (P<0.001). Small vessel disease correlated with coronary slow flow and extent of fibrosis, but did not with patients’ age, sex, and degree of left ventricular hypertrophy.

Conclusions— patients with FD with angina have perfusion defects, slow coronary flow, and luminal narrowing of intramural arteries. Small vessel disease may contribute to symptomatic limitation and progressive myocardial dysfunction.

Key Words: angina • cardiomyopathy • Fabry disease • ischemia • microcirculation

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