(Press-News.org) Sudden cardiac death is always a shocking, tragic event, especially when it occurs at a young age. But, for the first time, scientists are unraveling how genetic defects can help predict the risk of dying suddenly in individuals with one of the leading causes of this unfortunate phenomenon.
This knowledge could guide treatment and potentially lessen the occurrence of sudden cardiac death in patients with Long QT syndrome, a rare, inherited heart rhythm disorder. It could also provide insight into the assessment and treatment of the millions of people who experience cardiac arrhythmias – irregular heart rhythms that cause the heart to beat too fast or too slow and can lead to sudden death if not corrected.
The new study, published recently in the journal Science Translational Medicine, shows that the function of specific genetic mutations – namely, the defects these mutations cause – are strong predictors of risk of sudden death and other cardiac events in patients with Long QT.
The finding is especially relevant for individuals who have the condition but don't have particularly pronounced clinical risk factors, such as a very prolonged QT interval – the time it takes for the heart's electrical system to recharge after each heartbeat and get ready for the next (hence, the name "Long QT" syndrome). When the QT interval is prolonged, the heart is more susceptible to arrhythmias.
These tricky, in-between patients, who make up about 70 percent of the Long QT syndrome population, often fall into a treatment gray area. In the future, lead study author Coeli Lopes, Ph.D., hopes that physicians may be able to use mutation-specific information to better identify high-risk individuals in this group who should be followed more carefully and treated more aggressively.
"To our knowledge, this is the first time anyone's linked the activity of specific mutations to actual risk in patients," said Lopes, assistant professor at the Aab Cardiovascular Research Institute at the University of Rochester Medical Center. "We're literally going from studying mutant proteins in cells in the lab to risk assessment in the clinic, which is an exciting and very promising concept."
Long QT occurs most visibly in teens with otherwise healthy hearts and may go unnoticed until a stressful event, like swimming, jumping into cold water or hearing a particularly loud noise jolts the heart out of rhythm, leading to fainting, cardiac arrest or sudden death.
"Before we had such robust genetic information, we based risk solely on clinical measurements, such as the length of the QT interval and if patients had passed out in the past," said Arthur J. Moss, M.D., professor of Cardiology at the Medical Center and the world's foremost authority on the diagnosis and treatment of Long QT syndrome. "These results mean we can be much more specific in prescribing preventive therapy, which is terrific news for patients and their families."
Current treatment options for patients with Long QT include beta blockers, which relieve stress on the heart by slowing the heart rate, and implantable cardioverter defibrillators or ICDs, which detect irregular and potentially fatal heartbeats and shock the heart back into a normal rhythm. Better knowledge of risk will help physicians decide if patients need treatment with a beta blocker, an ICD or both.
In the study, researchers looked at the most frequent mutations found in patients with Long QT syndrome type 1, one of the most common forms of the disease, and analyzed their influence on ion channels – small pores or holes on the surface of each heart muscle cell. These channels open and close to let electrically charged particles flow into and out of the cell, generating the signal the heart needs to stop contracting and relax after pumping blood throughout the body.
When they compared the results with patient outcomes, they discovered that mutations that cause ion channels to open more slowly than they should were strongly associated with increased risk for cardiac events. Patients with these slow activating channels were twice as likely as patients with other mutations to die before the age of 30 or experience serious symptoms.
Even for patients who lacked telltale clinical symptoms, the presence of mutations linked with slow-to-open ion channels was still associated with an increased risk of cardiac events.
"This study creates a paradigm that we not only have to take into account the presence of mutations, but the potential consequences of mutations as well," noted Wojciech Zareba, M.D., Ph.D., director of the Heart Research Follow-up Program and an expert on Long QT. "Some mutations may be more benign and others less so and more research is needed to understand why this is the case."
The team looked at the function of 17 common mutations found in approximately 390 patients drawn from the International Long QT Registry. In the lab, they recreated the mutant proteins and put them in cells to study their effect on ion channels. They used clinical follow-up data from the registry to relate mutant function to cardiac risk.
While this process of testing mutant function is a starting point, Lopes says that in the future new, emerging stem cell technologies may allow physicians to take cells (such as skin cells) directly from patients and turn them into heart cells to more precisely determine mutant function.
"Similar to genetic testing, a simple, standardized way to test mutation function on a large scale is needed in order for this method to be widely adopted in clinical practice," noted Lopes.
###
The study was funded with a grant to Moss from the National Heart Lung and Blood Institute at the National Institutes of Health. In addition to Lopes, Moss and Zareba, Christian Jons, M.D, Jin O-Uchi, Ph.D, Ilan Goldenberg, M.D., Scott McNitt, M.S., and Jennifer L. Robinson from the Medical Center participated in the research. Matthias Reumann and John J. Rice, Functional Genomics and Systems Biology Group, IBM Thomas J. Watson Research Center; Nynke Hofman, Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam; Jorgen K. Kanters, Danish National Research Foundation Center for Cardiac Arrhythmias; Wataru Shimizu, National Cardiovascular Center, Suita, Japan; and Arthur A. M. Wilde, Heart Failure Research Centre, Academic Medical Centre, University of Amsterdam, also contributed to the study.
Genetic defects hold clues to risk for sudden cardiac death
2011-05-11
ELSE PRESS RELEASES FROM THIS DATE:
Wayne State researchers find new way to examine major depressive disorder in children
2011-05-11
DETROIT — A landmark study by scientists at Wayne State University published in the May 6, 2011, issue of Archives of General Psychiatry, the most prestigious journal in the field, has revealed a new way to distinguish children with major depressive disorder (MDD) from not only normal children, but also from children with obsessive compulsive disorder (OCD).
MDD is a common, debilitating disease prevalent in childhood and adolescence. Examination of cortical thickness in patients with MDD has not been widely studied, and WSU's team of researchers set out to determine ...
Brazil's health care system vastly expands coverage, but universality, equity remain elusive
2011-05-11
Two decades after Brazil's constitution recognized health as a citizen's right and a duty of the state, the country has vastly expanded health care coverage, improved the population's health, and reduced many health inequalities, but universal and equitable coverage remains elusive, experts from four major Brazilian universities and New York University have concluded.
According to their analysis—one of six articles published in the medical journal The Lancet as a special series on health in Brazil—while federal expenditures have nearly quadrupled over the past 10 years, ...
High-tech approach uses lights, action and camera to scrutinize fresh produce
2011-05-11
This release is available in Spanish.
High-tech tactics to carefully examine apples and other fresh produce items as they travel along packinghouse conveyor belts will help ensure the quality and safety of these good-for-you foods.
U.S. Department of Agriculture (USDA) scientists in Beltsville, Md., have developed and patented an experimental, cutting-edge optical scanning system that would use two different kinds of lighting, a sophisticated camera and other pieces of equipment to scrutinize produce-section favorites while they are still at the packinghouse.
The ...
Training to promote health
2011-05-11
This release is available in German.
Marianne has constant pain in her right knee at the moment – she hurt it when she took a tumble skiing in the Swiss Alps. Everything happened so quickly: The searing pain, the helicopter ride to hospital, the operation the following day, and then a week later the return home with crutches to rest in a reclining chair. Her aim now is to mobilize the operated knee and regain full mobility of the joint – something she'll achieve by following a targeted machine-based training plan drawn up by a physiotherapist.
In order to be able ...
Depression associated with poor medication adherence in patients with chronic illnesses
2011-05-11
People who are depressed are less likely to adhere to medications for their chronic health problems than patients who are not depressed, putting them at increased risk of poor health, according to a new RAND Corporation study.
Researchers found that depressed patients across a wide array of chronic illnesses such as diabetes and heart disease had 76 percent greater odds of being non-adherent with their medications compared to patients who were not depressed. The findings were published online by the Journal of General Internal Medicine.
The study is the largest systematic ...
Study: Lowering cost doesn't increase hearing aid purchases
2011-05-11
DETROIT – Lowering the cost of hearing aids isn't enough to motivate adults with mild hearing loss to purchase a device at a younger age or before their hearing worsens, according to researchers at Henry Ford Hospital.
A new study shows that simply lowering the cost of hearing aids – even by as much as 40% – does not improve hearing aid purchase for patients with partial insurance coverage or those who need to cover the entire cost out of pocket.
Only patients with full insurance coverage for hearing aids get them at a younger age and with significantly less hearing ...
Zebrafish models identify high-risk genetic features in leukemia patients
2011-05-11
SALT LAKE CITY—Leukemia is the most common childhood cancer; it also occurs in adults. Now researchers working with zebrafish at Huntsman Cancer Institute (HCI) at the University of Utah have identified previously undiscovered high-risk genetic features in T-cell acute lymphocytic leukemia (T-ALL), according to an article published online May 9, 2011, in the cancer research journal Oncogene. When compared to samples from human patients with T-ALL, these genetic characteristics allowed scientists to predict which patients may have more aggressive forms of the disease that ...
2 new studies describe likely beneficiaries of health care reform in California
2011-05-11
According to two new policy briefs from the UCLA Center for Health Policy Research, the majority of state residents likely to be eligible for federally mandated health insurance coverage initiatives in California in 2014 are also those who may be least likely to excessively use costly health services: men, singles and those of working age.
As a result of last year's passage of the federal Patient Protection and Affordable Care Act (ACA), up to 4.57 million previously uninsured or underinsured Californians may be eligible for coverage, either through an expansion of ...
Less than half of patients with MS continually adhere to drug therapies for treatment: Study
2011-05-11
TORONTO, Ont., May 11, 2011 — Disease-modifying drugs (DMDs) are injected medications used to slow the progression of multiple sclerosis (MS), and have been shown to reduce the frequency and severity of relapses. But according to a new study led by St. Michael's Hospital and the Institute for Clinical Evaluative Sciences (ICES), adherence to all DMDs is low, with less than half of patients, or 44 per cent, continually adherent after two years.
"There are a number of reasons why adherence to therapies of proven value might be low," says Dr. Paul O'Connor, director of the ...
Harnessing the energy of the Sun: New technique improves artificial photosynthesis
2011-05-11
This discovery will make it possible to improve photoelectrochemical cells. In the same way that plants use photosynthesis to transform sunlight into energy, these cells use sunlight to drive chemical reactions that ultimately produce hydrogen from water. The process involves using a light-sensitive semi-conducting material such as cuprous oxide to provide the current needed to fuel the reaction. Although it is not expensive, the oxide is unstable if exposed to light in water. Research by
Adriana Paracchino and Elijah Thimsen, published May 8, 2011 in the journal Nature ...