title: Microfibrillar cardiomyopathy: An infiltrative heart disease resembling but distinct from cardiac amyloidosis.
abstract: Microfibrils-small, ubiquitous components of the extracellular matrix in many tissues-generally have not been recognized as causing infiltrative heart disease, except in a group of cardiac transplant patients treated with cyclosporin. Microfibrils are often associated with elastic tissue and contain the glycoprotein fibrillin, the P component of amyloid, and bound fibronectin. A genetically determined abnormality of fibrillin caused by point mutations of fibrillin genes recently was reported as the cause of Marfan's syndrome. However, to date, no abnormalities of increased fibrillin tissue deposition have been observed. In the last two years, while examining right ventricular endomyocardial biopsies, in four patients we noted abnormal histology distinct from the usual type of congestive cardiomyopathy but with a strong resemblance to amyloidosis. The patients presented with unexplained ventricular tachycardia (N = 3) and/or congestive heart failure (N = 2). Biopsies revealed subendocardial, interstitial, and perivascular hyaline eosinophilic fibrillar material that did not stain with Congo red. Electron microscopy revealed that this material was organized into bundles of tangled microfibrils composed of twisted and tubular structures measuring up to 17 nm wide, which did not resemble amyloid or cyclosporin-associated microfibrils. Immunoelectron microscopy of the index case, using monoclonal antibody to fibrillin, specifically identified these structures as fibrillin microfibrils; fibronectin also was bound to the interstitial microfibrils. We believe that the subendocardial and interstitial deposition of microfibrils in these four symptomatic patients may represent a new type of infiltrative cardiomyopathy, similar to but distinct from cardiac amyloidosis. We do not know yet if this disorder is genetic or acquired, or if the prognosis is better than that of cardiac amyloidosis. However, atypical cases of primary cardiac amyloidosis should be reevaluated in light of these findings.
authors.affiliation: From the Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA; From the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Factor
authors.affiliation: From the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Menegus
authors.affiliation: From the Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Kress
authors.affiliation: From the Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cho
authors.affiliation: From the Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Fisher
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon, USA; Department of Biochemistry and Molecular Biology, Shriners Hospital for Crippled Children, Portland, Oregon, USA.
authors.forename: L Y
authors.initials: LY
authors.lastname: Sakai
authors.affiliation: From the Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Goldfischer