Imaging test may detect gene for genetic cardiac disease

Monday, June 3, 2002 - Boston

Researchers at Brigham and Women’s Hospital (BWH) have found that a simple imaging test may identify individuals who carry a specific gene that may put them at risk for developing hypertrophic cardiomyopathy (HCM), a disease that causes thickening of the heart and early sudden death. The findings from this study are published in the June 3^rd issue of Circulation: Journal of the American Heart Association.

"Many individuals with the most common genetic mutation do not manifest hypertrophy until later in life. Therefore, it is very challenging to identify the disease in time to help people," said lead author Scott Solomon, M.D., director of noninvasive cardiology at BWH. "Thickened hearts indicate HCM, but not all individuals will develop this thickening. We wanted to find a way to diagnose the disorder earlier in the disease process."

HCM is the most common cause of cardiac death among young people and affects one in every 500 individuals, including professional athletes. It is characterized by an enlargement of the left ventricle, the heart’s main pumping chamber. This enlargement results in a thickening of the walls of the heart, which then prevents the heart from functioning properly.

Most patients develop HCM by inheriting a gene that predisposes them to the disease and only one parent needs to be a carrier of the gene in order to transfer it to the child. More than 140 disease-causing mutations for HCM have been identified in up to 10 genes. The most common is a mutation in the gene for the beta-myosin heavy chain – a major component in heart muscle. Myosin is one of the proteins responsible for contraction of heart muscle.

The study examined three groups of individuals, ranging in age from 24 to 36, including 18 patients with left ventricular hypertrophy and a genetic defect in the beta-myosin gene for cardiomyopathy, 18 patients with the genetic defect but did not have hypertrophy, and 36 healthy individuals.

Researchers used a relatively new imaging technique called Doppler tissue imaging (DTI), a real-time noninvasive ultrasound procedure that shows how fast the heart muscle moves during contraction and relaxation. They found that individuals who had HCM tended to have lower velocities during the relaxation phase of the cardiac cycle.

Researchers also discovered that the left ventricular ejection fraction was significantly higher and early diastolic velocities were significantly lower in those with the beta-myosin gene mutation, regardless of whether they had left ventricular hypertrophy.

A cut-off velocity of 13.5 centimeters per second (cm/sec) was determined by researchers as being about 86 percent accurate in identifying individuals with the genetic defect. The combination of ejection fraction of greater than 68 percent and early diastolic myocardial velocity of less than 15 cm/sec was 100 percent specific and 44 percent sensitive in predicting affected genotype.

"Although velocity alone was not sufficiently sensitive as a sole diagnostic criterion, the combination of early diastolic myocardial velocity and ejection fraction was highly predictive of the gene mutation in individuals without overt manifestations of the disease," said Dr. Solomon.

Brigham and Women’s Hospital is a 719-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare System, an integrated health care delivery network. Internationally recognized as a leading academic health care institution, Brigham and Women’s Hospital is committed to excellence in patient care, medical research, and the training and education of health care professionals. The hospital’s preeminence in all aspects of clinical care is coupled with its strength in medical research. A leading recipient of research grants from the National Institutes of Health, Brigham and Women’s Hospital conducts internationally acclaimed clinical, basic and epidemiological studies.

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