Now, genomic medicine has helped Mayo Clinic researchers find a renewed use for a test once deemed ineffective in detecting a cardiac condition sometimes cited as the cause of previously unexplained sudden deaths.
"This is a test we use to determine if patients are at risk of long QT syndrome," says Michael J. Ackerman, M.D., Ph.D., director of the Long QT Syndrome Clinic at Mayo Clinic and the principal investigator of a study that appears in the May issue of Mayo Clinic Proceedings. "We feel the best place for patients to have their first episode is under medical care rather than while running down the street."
Mayo Clinic researchers discovered a unique response among certain patients with long QT syndrome when epinephrine was infused into their bodies, while being monitored with a 12-lead electrocardiogram. In the past when the genetic sub-types of long QT were not known, the response to adrenaline was scattered and not definitive.
"Human Genome Project insights have translated into a revival of an old clinical test," says Dr. Ackerman. "It was rediscovered as potentially useful when you understand the response to the test depends on the underlying genetic defect."
The study in Mayo Clinic Proceedings identifies a specific response in people with long QT syndrome 1 (LQT1) compared with other genotypes of long QT syndrome. LQT1 affects about 1 in 20,000 people and can have effects ranging from fainting to sudden death. It is suspected in some unexplained drownings.
Along with Dr. Ackerman, other Mayo Clinic researchers involved in the study were: Anant Khositseth, M.D.; David J. Tester, B.S.; Joseph B. Hejlik, R.N.; Win-Kuang Shen, M.D. and Co-Burn Porter, M.D.
"The present work represents a welcome bridge between the molecular genetics of cardiac ion channelopathies and the application of this knowledge in the diagnosis and management of these patients," writes James C. Perry, M.D., of Children’s Hospital in San Diego, Calif., in an accompanying editorial.
Long QT syndrome is the first genetically defined type of arrhythmia to be understood at the molecular level.
In each beat, the heart has to electrically fire to tell the muscle to squeeze and then it has to reset itself in preparation for the next beat. Long QT syndrome is a genetic condition that affects the heart’s electrical system where the electrical recharging process (measured by the QT interval on the ECG) is longer than normal. Usually, patients have no problem with this condition, but certain triggers like swimming, intense physical exertion or being suddenly startled or frightened can set it off, causing fainting spells, seizures or even death from a fatal heart rhythm called ventricular fibrillation. Long QT syndrome affects approximately 1 in 5,000 people.
Those at risk for long QT syndrome include: those who experience fainting spells due to emotion, exercise or exertion; some relatives of those with long QT syndrome; those with a family history of seizures, Sudden Infant Death Syndrome and sudden death; and those who experience an unexplained near-drowning. These individuals should get an electrocardiogram because the prolonged QT interval is often detected by the test. Patients with long QT syndrome can lead normal lives with some restrictions. Those restrictions include: no swimming without a buddy, no competitive sports and taking medication daily.
The study looked at 37 patients between May 1999 and April 2001 who were genotyped with long QT syndrome in Mayo’s Sudden Death Genomics Laboratory directed by Dr. Ackerman. Their results were contrasted with 27 healthy volunteers. The patients were monitored continuously with a 12-lead ECG during the epinephrine QT stress test.
The test takes about an hour to conduct. The patient is lying on his or her back when the epinephrine is infused into the arm intravenously. It is done under medical supervision and the patient is fitted with defibrillator pads just in case they have a cardiac episode. However, more than 100 of these epinephrine challenges have been conducted to date without any complications, Dr. Ackerman said.
"This report should result in wide application of the epinephrine test to identify patients with the LQT1 genotype," writes Dr. Perry in his editorial.
Dr. Ackerman said further testing is needed to determine if the paradoxical response to adrenaline observed in this initial study is specific only for this particular genetic abnormality of long QT subtype 1.
Mayo Clinic Proceedings is a peer-reviewed and indexed general internal medicine journal, published for 75 years by Mayo Foundation, with a circulation of 130,000 nationally and internationally.
John Murphy
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e-mail: newsbureau@mayo.edu
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