CLINICAL STUDY: CARDIOMYOPATHY
Immunohistologic evidence of myocardial disease in apparently healthy relatives of patients with dilated cardiomyopathy
Niall G. Mahon, MD*,*,
Brendan P. Madden, MD*,
Alida L. P. Caforio, MD, PhD ,
Perry M. Elliott, MD*,
Aldwyn J. Haven, BSc*,
Bruce E. Keogh, MD ,
Michael J. Davies, MD, PhD* and
William J. McKenna, MD*
* Department of Cardiological Sciences, St. George’s Hospital Medical School, London, United Kingdom
Division of Cardiology, Department of Experimental and Clinical Medicine, University of Padova, Padova, Italy
Department of Cardiothoracic Surgery, Queen Elizabeth Hospital, Birmingham, United Kingdom
Manuscript received August 10, 2001;
revised manuscript received October 24, 2001,
accepted November 2, 2001.
* Reprint requests and correspondence: Dr. Niall G. Mahon, Department of Cardiology/F25, Section of Heart Failure Transplant Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
mahonn{at}ccf.org
OBJECTIVES: This study investigated whether apparently healthy relatives of patients with idiopathic dilated cardiomyopathy (DCM) who have left ventricular enlargement (LVE) have biopsy evidence of underlying myocardial disease.
BACKGROUND: Left ventricular enlargement with normal systolic function is common among asymptomatic relatives of patients with DCM. Although there is circumstantial evidence to suggest that LVE may be a marker of early DCM, its pathophysiologic significance remains uncertain.
METHODS: Over six years, 767 asymptomatic relatives of 183 consecutive patients with DCM were evaluated: 37 (5%) had DCM and 104 (14%) had LVE (left ventricular end-diastolic dimension >112% predicted) with normal systolic function. Right ventricular biopsy was performed in 32 relatives with LVE, 14 patients with symptomatic DCM and 6 control subjects with normal ventricular function undergoing elective coronary artery bypass graft surgery. Histologic and immunohistochemical analyses, including quantitative double immunofluorescence, were performed for leukocyte markers (CD3 and CD68), intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen class II antigens (DR and DQ).
RESULTS: Histologic findings consistent with DCM were present in 50% of the patients with DCM, 25% of the relatives with LVE and 0% of the control subjects. The median CD3 count was 2.4/mm2 in patients with DCM, 4/mm2 in relatives with LVE and 0 in control subjects (p = 0.04). Using a threshold of >7 cells/mm2, 21% of patients with DCM and 25% of relatives with LVE were CD3-positive (p = 0.01). Quantitative analysis demonstrated DR expression on 55.8 ± 22.8%, 63.5 ± 18.8% and 30.9 ± 15.7% of the endothelial surface in patients with DCM, relatives and control subjects, respectively (p = 0.003). Corresponding values for ICAM expression were 35.6 ± 15.1%, 36.7 ± 14.5% and 17.3 ± 7.9% (p = 0.013). When combining inflammatory and histologic changes, 28 (86%) of LVE, 14 (100%) of DCM and no control biopsies were abnormal (p < 0.001).
CONCLUSIONS: Most asymptomatic relatives of patients with DCM with LVE have histopathologic and immunopathologic findings similar to those of patients with established disease. Clinical identification and follow-up of such individuals are warranted to prevent presentation with advanced DCM and to enable assessment of interventions aimed at attenuating disease progression.
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Abbreviations and Acronyms
| | LVEDD | | BSA | | body surface area | | DCM | | dilated cardiomyopathy | | HLA | | human leukocyte antigen | | ICAM | | intercellular adhesion molecule | | IgG | | immunoglobulin | | LVE | | left ventricular enlargement | | LVEDD | | left ventricular end-diastolic dimension |
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