Genetic testing can identify ischemic and nonischemic heart failure

November 06, 2004

Researchers at Johns Hopkins have shown that genetic testing can be effectively used to distinguish between heart failure patients who suffer from ischemic or nonischemic forms of the disease. Using groupings or clusters of a patient's gene expression to compare to a diseased "test" set that identifies the cause of heart failure, the Hopkins team assembled a 90-gene profile to determine which type of heart failure had most likely developed. Results showed the test profile to be highly accurate, with 90 percent specificity.

The findings could, if affirmed and adapted to a standardized and affordable test format, someday aid physicians in the diagnosis of heart failure and help determine which kind of therapy is best to use for the condition. In ischemic heart disease, the patient's arteries have narrowed and the heart cannot pump normally because blood flow (and thus oxygen) is often restricted to the heart muscle. In nonischemic forms of the disease, the heart cannot pump normally because the heart muscle has often enlarged for other reasons, such as physical deformity or alcohol abuse. Both conditions can lead to cardiac arrest or more gradual heart failure as the muscle weakens over time.

"The gene expression differences between various forms of cardiovascular disease are poorly understood, despite the fact that we know there are major differences in what is happening at the cellular level," said Michelle Kittleson, M.D., cardiology fellow at the Johns Hopkins Heart Institute and lead author of the study to be presented at the American Heart Association's Scientific Sessions 2004 on Nov. 6, as a finalist for the Samuel A. Levine Young Clinical Investigator Award.

"Our study shows that gene expression profiling for heart failure patients is not only possible, but accurate as well. Based on these initial findings, we hope to close the gaps in our understanding of the gene expression patterns underlying heart failure and treatments for the illness. Ultimately, we hope to be able to use genetic profiling to classify patients according to their risk of developing all kinds of heart disease."

To create a gene expression profile, or test, the Hopkins team collected 16 biopsy tissue samples, six from patients with the ischemic form of the disease and 10 from nonischemic cases, all with end-stage heart failure. Most of the test samples came from heart transplant patients at Hopkins in the last 20 years.

Using a biostatistical technique called prediction analysis, the researchers identified the 90 genes that best distinguished the two kinds of heart failure. The large number of genes used also improved accuracy of the test.

This gene profile was later validated by testing it against 38 other tissue samples, including 14 provided from the University of Minnesota. These test samples involved tissue from all stages of heart failure, including end-stage, post-LVAD (a type of heart surgery) and biopsy samples from newly diagnosed patients.

"Now that we know we can genetically profile heart patients according to ischemic and nonischemic heart disease, our next step is to develop a test that can be used in a clinical setting," said senior study author and cardiologist Joshua Hare, M.D., a professor of medicine at the Heart Institute. "Ischemic patients need to be monitored more closely in case they develop drug resistance and require surgery to unblock clogged arteries. Knowing which patients to treat and how closely to monitor them could significantly improve how well physicians manage the disease and, consequently, improve health outcomes."
-end-
This one-year study was funded by the National Institutes of Health. Further assistance with statistical analysis was provided from the Johns Hopkins Bloomberg School of Public Health.

Other investigators in this research, conducted solely at Johns Hopkins, were Shui Ye, M.D., Ph.D.; Rafael Irizarry, Ph.D.; Khalid Minhas, M.D.; Gina Edness, R.N.; John Conte, M.D.; Giovanni Parmigiani, Ph.D.; Leslie Miller, M.D.; Yingjie Chen, M.D., Ph.D.; Jennifer Hall, Ph.D.; and Joe Garcia, M.D.

Johns Hopkins Medicine

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.