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CLINICAL STUDIES

Clinical profiles of four large pedigrees with familial dilated cardiomyopathy

Preliminary recommendations for clinical practice

^a Heart Failure Treatment Program, Division of Cardiology, Department of Medicine, Oregon Health Sciences University, Portland, Oregon, USA

Manuscript received July 8, 1998; revised manuscript received March 29, 1999, accepted May 16, 1999.

Reprint requests and correspondence: Dr. Ray E. Hershberger, Cardiology-UHN62, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201 or www.fdc.to
hershber{at}ohsu.edu

OBJECTIVES

This study aimed to characterize the clinical profile of familial dilated cardiomyopathy (FDC) in the families of four index patients initially diagnosed with idiopathic dilated cardiomyopathy (IDC) and to provide clinical practice recommendations for physicians dealing with these diseases.

BACKGROUND

Recent evidence indicates that approximately one-half of patients diagnosed with IDC will have FDC, a genetically transmissible disease, but the clinical profile of families screened for FDC in the U.S. has not been well documented. Additionally, recent ethical guidelines suggest increased responsibilities in caring for patients with newly found genetic cardiovascular disease.

METHODS

After identification of four families with FDC, we undertook clinical screening including medical history, physical examination, electocardiogram and echocardiogram. Diagnostic criteria for FDC-affected status of asymptomatic family members was based on left ventricular enlargement (LVE). Subjects with confounding cardiovascular diagnoses or body mass indices >35 were excluded.

RESULTS

We identified 798 living members from the four FDC pedigrees, and screened 216 adults and 129 children (age <16 years). Twenty percent of family members were found to be affected with FDC; 82.8% of those affected were asymptomatic. All four pedigrees demonstrated autosomal dominant patterns of inheritance. The average left ventricular end-diastolic dimension was 61.4 mm for affected and 48.4 mm for unaffected subjects, with an average age of 38.3 years (±14.6 years) for affected and 32.1 years for unaffected subjects. The age of onset for FDC varied considerably between and within families. Presenting symptoms when present were decompensated heart failure or sudden death.

CONCLUSIONS

We propose that with a new diagnosis of IDC, a thorough family history for FDC should be obtained, followed by echocardiographic-based screening of first-degree relatives for LVE, assuming their voluntary participation. If a diagnosis of FDC is established, we suggest further screening of first-degree relatives, and all subjects with FDC undergo medical treatment following established guidelines. Counseling of family members should emphasize the heritable nature of the disease, the age-dependent penetrance and the unpredictable clinical course.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   BMI = body mass index   ECG = electrocardiogram   FDC = familial dilated cardiomyopathy   HCM = hypertrophic cardiomyopathy   ICD = internal cardiac defibrillator   IDC = idiopathic dilated cardiomyopathy   LVE = left ventricular enlargement   LVEDD = left ventricular end-diastolic dimension   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   OHSU = Oregon Health Sciences University   SOLVD = Studies of Left Ventricular Dysfunction

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