Progressnotes - October/November 2012
- About MUSC Health
A simple blood test developed by scientists at the Medical University of South Carolina’s Heart and Vascular Center may revolutionize the treatment of atrial fibrillation (AF), which is the most common heart rhythm disorder, striking 2.2 million Americans. Up to 5 percent of people 65 and older have AF. With our rapidly aging population, AF is well on its way to becoming a momentous public health concern. Treating it racks up $26 billion annually in health care costs. The disorder also is considered to be the leading cause of strokes in the United States. The total cost of treating stroke in this country is estimated to be $43 billion.
“Treatment of AF has been hampered by ineffectiveness of drugs. Additionally, attempts to terminate AF with cardioversion work for only about half of patients in the first six to 12 months,” said Michael R. Gold, M.D., Ph.D., MUSC’s chief of cardiology. “Consequently, a simple means to identify patients in whom cardioversion would effectively terminate AF would be beneficial in terms of saving both time and money,” Gold said.
Gold and his colleague, Rupak Mukherjee, Ph.D., developed the blood test, which measures protein signatures unique to patients with AF. The test has not yet been approved by the Food and Drug Administration.
“We are looking at proteomics, rather than at biomarkers, which looks at the proteins in blood or urine. It is simpler than genetic testing,” Gold and Mukherjee said.
Gold is the Michael E. Assey Professor of Medicine. He is a leading authority on electrophysiology, adult cardiology and arrhythmias and is a pioneer in the development of new defibrillation techniques and pacing for congestive heart failure.
Mukherjee is an associate professor of surgery whose research interests include mechanisms of structural remodeling of the heart related to alterations in mechanical stress and arrhythmias. He is a member of the MUSC laboratory group that made important discoveries concerning a unique enzyme system in the human myocardium that contributes to changes in size and shape – or remodeling – of the heart.
In developing the test, Gold and Mukherjee studied a family of these enzymes, the matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs (TIMPs), to assess their role in matrix remodeling in AF. The cardiac extracellular matrix structure is controlled by the MMPs, whose activity maintains a balance between connective tissue synthesis and degradation. MMP gene polymorphisms, by modifying the level of gene expression, seem to affect atrial structural remodeling and AF recurrence rate.
Gold and Mukherjee’s experiments subsequently verified that changes in the MMP/TIMP balance play an important role in the structural, functional and clinical manifestations of AF. These findings formed the basis of a new blood test, now patented, in which plasma MMP/TIMP levels could be used as diagnostic/prognostic biomarkers and to direct clinical treatment of AF patients. Such treatments may include early initiation of antiarrhythmic drugs or ablation techniques to eliminate the triggers of AF. Under the leadership of Dr J. Marcus Wharton, the Frank Tourville Professor of Medicine and Chief of Cardiac Electrophysiology, and Dr. Gold, MUSC has become the leading center for the treatment of AF in the region.
An American Heart Association study reported that AF patients are hospitalized twice as often and have three times the rate of multiple hospitalizations and four times as many cardiovascular admissions as patients without the disorder.
A patient may spontaneously alternate between AF and a normal rhythm (paroxysmal atrial fibrillation) or may continue with AF as the dominant cardiac rhythm without reversion to the normal rhythm without electrical shocks or antiarrhythmic drugs (persistent AF). Atrial fibrillation is often asymptomatic but may result in symptoms of palpitations, fainting, chest pain or even heart failure. These symptoms are especially common when AF results in a heart rate that is either too fast or too slow. In addition, the erratic motion of the atria leads to blood stagnation (stasis), which increases the risk of blood clots that may travel from the heart to the brain and other areas. Thus, AF is an important risk factor for stroke, the most feared complication of AF.
AF is usually accompanied by symptoms related to either rapid heart rate or embolization. Rapid and irregular heart rates may be perceived as palpitations, lead to exercise intolerance and occasionally produce angina and congestive symptoms of shortness of breath or edema. Sometimes the arrhythmia will be identified with the onset of a stroke or a transient ischemic attack. It is not uncommon to identify AF on a routine physical examination or electrocardiography (characteristic findings include absence of P waves, unorganized electrical activity in their place, and irregularity of R-R interval due to irregular conduction of impulses to the ventricles) as it may be asymptomatic in some cases.
For more information, call MEDULINE at 1-800-922-5250 or 843-792-2200 or visit the MUSC Physician Portal.
This article originally appeared in the October 2011 issue of Progressnotes.