HCM detection rates doubled when genetic testing and imaging information are combined

Currently that genetic test correctly detects HCM only 40 percent of the time. But coupled with imaging information, the detection power of the test nearly doubles, to 79 percent, says Steve Ommen, M.D., director of Mayo's HCM Clinic and co-lead investigator of the Mayo Clinic research team.

These results suggest the combined approach of an echocardiography-guided genetic test may be more helpful for families undergoing genetic counseling, and more cost-effective to perform, he says.

The Mayo Clinic team's report appears in the current edition of Mayo Clinic Proceedings (http://www.mayoclinicproceedings.com/). Hypertrophic cardiomyopathy is most often a hereditary condition in which the heart muscle thickens and enlarges, and the cells in the tissue become disorganized. As a result, the pumping function of the heart can be altered. HCM affects one in 500 people and is the most common identifiable cause of sudden death in young people, particularly athletes. Genetic screening for mutations that cause HCM gives parents advance knowledge they can use to prepare for treatment, ranging from medication to defibrillator implantation, to surgery and lifelong medical surveillance for worsening symptoms.

Significance of the Mayo Clinic Research
Boosting the sensitivity of the HCM detection rate with the image-gene screen combo can help physicians more accurately identify which families may benefit most from genetic testing for HCM, and then more accurately counsel those families. In such counseling, genetic information from uncles, aunts and grandparents, too -- not just the parents -- can yield insights into hereditary patterns.

Until now, physicians and genetic counselors have been hindered in their ability to give families an accurate picture of the risk of passing along the HCM trait.

"Our finding helps families two ways: short term and in the future," Dr. Ommen says. "In terms of the most immediate application, the echocardiographic shape of the heart can help physicians give families more meaningful and accurate information about the role of genetic testing for that specific family. In terms of the future, it presents a research opportunity to explore how and why this distinct trait of heart anatomy occurs -- which hopefully will give us a better handle on HCM all around and help us design interventions to prevent or correct this defect."

Adds Michael Ackerman, M.D., Ph.D., the study's co-lead investigator and director of Mayo's Sudden Death Genomics Laboratory: "In moving basic research findings from the lab into the clinic where they can help patients, this may be one of the most substantive observations in the past 15 years linking gene mutations to specific symptoms that patients experience."

"Fundamentally, we have discovered that the two most common subtypes of HCM have markedly distinct genetic underpinnings," he says.

The Meaning of Shape
The researchers examined two distinct anatomical heart shapes. One shape is described as sigmoid, and the other is called reverse curvature. In their report, the researchers focus on an unusual feature that is more commonly observed in the hearts of patients diagnosed with HCM after age 50. The hearts of younger people with HCM generally lack this distinctive feature of heart anatomy known as sigmoid ventricular septum. It is a variance in the shape in one wall of the heart, and it has long been associated with a milder form of the disease. By comparison, the other distinctive shape -- reverse curvature of the ventricular septum -- dramatically alters the contours of the chamber. However, until the current era of genomic medicine brought the ability to link structural changes with specific gene activity, it was not clear that this distinctive structural feature was linked to specific mutations that cause HCM.

About the Mayo Clinic Study
The researchers examined 382 unrelated patients in the Mayo Clinic Hypertrophic Cardiomyopathy Clinic over a four-year period, analyzing eight known HCM-susceptibility genes. These eight genes comprise the available clinical genetic test for HCM. Next -- and without prior knowledge of the results of the patients' genetic profiles -- the researchers evaluated traditional medical exam data, including patient medical history, and anatomical and functional findings, such as blood pressure and echocardiography images. Echocardiography is a common noninvasive way to make a moving picture of the heart's structure and function using ultrasound. It transmits sound waves through the heart and records them on an electronic sensor to create a moving picture.

Findings
In the final step, the researchers matched the gene screening results to traditional exam results -- and found a consistent correlation between heart muscle shape and the presence of HCM-associated mutations. Regardless of age, if the heart muscle had the sigmoid shape, the yield of the genetic test was only 8 percent compared to 79 percent when the shape was reverse curvature.