Hypertrophic cardiomyopathy is an autosomal dominant disorder and the most common cause of sudden cardiac death in the young; it affects 1 in every 500 individuals, including professional athletes. More than 140 causative mutations have been identified in up to 10 genes. The most common mutation is in the gene sequence for the beta-myosin heavy chain.

"However, many individuals with the most common mutation do not manifest hypertrophy until later in life; therefore, it is very challenging to identify the disease in time to help people," says Scott Solomon, M.D., lead author. "Thickened hearts indicate hypertrophic cardiomyopathy, but not all individuals will develop this thickening. We wanted to find a way to diagnose the disorder earlier in the disease process."

Solomon and researchers led by Carolyn Y. Ho, M.D., used a relatively new imaging technique called Doppler tissue imaging, which is a real-time noninvasive ultrasound procedure that shows the speed of myocardial cell activity during contraction and relaxation.

Researchers found that individuals with the genotype for hypertrophic cardiomyopathy tended to have lower velocities during the relaxation phase of the cardiac cycle.

Three groups of individuals ages 24 to 36 years were studied: 18 individuals with left ventricular hypertrophy and a mutation in the beta-myosin gene, 18 people with the mutation but no clinical hypertrophy, and 36 healthy individuals.

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

Researchers determined a cut-off velocity of 13.5 centimeters per second (cm/sec) as roughly 86 percent accurate in identifying individuals with the mutation. 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," Solomon says.

According to Robert Roberts, M.D., who wrote an accompanying editorial: "Familial hypertrophic cardiomyopathy is a most unusual and puzzling disease. The heart is supernormal and thus not infrequently seen in the most elite of athletes. It is treacherous since sudden death is often the first manifestation, yet elegantly clothed in deception since the defect is present from conception."

Roberts notes that there are several barriers to the clinical application of this knowledge.

"Multiple genes make screening individuals formidable in terms of cost and time, thus there is a need to develop a rapid and accurate method. This new technique may be one answer," says Roberts.

Hypertrophy seldom develops prior to puberty. The new tissue Doppler imaging offers some promise for diagnosis in younger individuals, says Roberts. He says it also demonstrates that diastolic abnormalities may be an early sign and potential trigger leading to hypertrophy.

"Advances like this one may make a difference with this disease as well as help us understand and prevent sudden death in our population, particularly in young athletes," says Roberts.