Drs. Brian Go and Dr. Vernon Anderson are cardiologists at the Hermann Heart Center in Houston. Dr. Anderson, an Associate Professor, University of Texas Medical School, is a world renowned expert on unstable angina and interventional cardiology.
When the heart muscle is deprived of sufficient blood flow or oxygen, intense chest pain, called angina, occurs. In unstable angina (UA), the angina happens more often and with increasing severity, sometimes even at rest. UA is one of the most frequently cited diagnoses for hospital admissions in the United States and is, unfortunately, associated with significant short-term disability and death. Until recently, the condition was easily missed because the electrocardiogram, the doctor's standard technique for detecting heart problems, is, usually, completely normal in the presence of UA. Today, however, equipped with new blood tests measuring levels of specific enzymes (CK-MB, troponin-T, troponin-I, CK-MB isoforms and myoglobin) that rise with heart tissue damage, doctors are able to identify unstable angina earlier.
What Causes the Symptoms?
In certain people, who have high levels of circulating fats (lipids), extra patches (called plaques) of lipid and cells build out from the walls of their arteries. If a plaque erodes or tears, platelets and other elements of the blood clotting system are activated and, eventually, a clot (thrombus) forms. More platelets continue to enter the area and the thrombus continues to grow until blood flow past the plaque is reduced. The artery wall, damaged by years of contact with the fat-laden plaques, can't expand wide enough to allow more blood flow. Tissues dependent on the oxygen-rich blood are deprived of oxygen. Oxygen deprivation of the heart muscle produces the pain of angina. Increasing evidence suggests that inflammation from an infectious agent may play a key role in UA and it is possible that, one day, angina patients may benefit from treatment with an antibiotic which should help prevent the initial deposit of fat into the arterial walls.
With our current diagnostic tools, we do not know which blockage will cause unstable, as opposed to stable and more easily treatable, angina. The degree of artery obstruction does not differ between stable and unstable angina. In fact, how much blockage there is in a coronary artery does not even predict whether medical therapy will be beneficial. X-ray pictures, taken with special contrast, that demonstrate the blood-containing lining of the artery suggests that the type of coronary lesion might determine the clinical course.18 Patients with UA often have plaques that have hazy and irregular borders (which suggests that the artery lining may have a blood clot sticking to a broken plaque). Because unstable plaques seem to possess elevated temperatures, doctors may, one day, be able to identify them with a thermal sensor.
Is Unstable Angina Serious?
Unless there is evidence of a heart attack, patients are treated with observation, monitoring and an intensive medical regimen, including blood thinners, artery dilator drugs to lower the heart rate and blood pressure, and platelet inhibitors. Although more than 80% of patients with UA stabilize comfortably on intensive medical therapy, there is no standard way to predict which of these patients are at increased risk for a heart attack or cardiac death. The electrocardiogram (ECG), a snapshot in time, isn't of much help in following this dynamic, ever changing condition. As a result, continuous ECG monitoring has been proposed as a better way to identify patients at increased risk for heart problems.
New Markers for Heart Damage
There are, however, several indicators of heart tissue damage. Within the first 24 hours following an attack of unstable angina, blood levels of specific enzymes, CK-MB, the troponins (troponin-T and troponin-I), rise and may remain elevated for up to 11 days. These enzyme markers are very sensitive and can detect even minor heart tissue damage. Elevation in troponin levels in UA patients carries a worse prognosis.
If You Have UA, What Can Be Done?
The twin goals of therapy are to improve blood flow to the heart tissue and to stabilize the plaque so that it doesn't continue to promote clot build-up. Many drugs are now available.
Aspirin is useful because it slows down platelet clumping and deposition on the plaque inside the artery and greatly decreases the incidence of heart attack and death. Intravenous heparin inhibits further blood clot formation and, in combination with aspirin, is especially effective. Nitroglycerin dilates coronary arteries and improves blood flow. It is given IV to high-risk patients and to those with recurrent chest pain. Patients can be changed to an oral or topical form, once chest pain episodes subside and stabilization is achieved. Beta-blockers lower the heart rate and blood pressure which decreases the workload of the heart and have been found to help prevent progression of UA to heart attack and death. For patients in whom beta-blockers are not a good idea, calcium antagonists have helped prevent the UA to heart attack progression.
New Drugs
Antiplatelet Agents
An emerging new class of drugs, IIb/IIIa receptor inhibitors, prevent clot formation by blocking receptors on platelets. These drugs are all given intravenously and include eptifibatide (Integrilin®), tirofiban (Aggrastat®), and abciximab (ReoPro®). Taken together with heparin, they greatly reduce the occurrence of heart attacks among UA patients. One note of caution — because heparin can also cause bleeding, the doctor must carefully adjust the dosage to the patient's weight. An oral form of these receptor inhibitors is now being evaluated and may offer the possibility of long-term administration and extended effects.
Two other new drugs, ticlopidine (Ticlid®) and clopidogrel (Plavix®), both taken orally, also inhibit the activity of platelets, but by a different pathway. Like the receptor-inhibitors, they have been shown to decrease the incidence of heart attack and death in patients with UA. Unlike aspirin, however, beneficial effects of ticlopidine may not be apparent for at least a week because it takes a while for it to build up in the body. Both clopidogrel and ticlopidine can be used in patients who have an intolerance to aspirin. Combination therapy that includes aspirin and either ticlopidine or clopidogrel has not been fully evaluated but, theoretically, may offer significant advantages.
Antithrombins (Low-Molecular-Weight Heparin)
Low-molecular-weight heparin (LMWH) offers benefits over standard heparin. It can be especially effective when added to aspirin and will not, unlike standard heparin, cause an increase in major bleeding. Existing LMWHs include dalteparin (Fragmin®), nadroparin (Fraxiparin®) and enoxaparin (Lovenox®).
Surgical Treatments
For UA patients, the central therapeutic question is when to perform coronary angiography(X-ray pictures with special contrast that demonstrate the blood containing lining of the artery), coronary angioplasty ("balloon surgery" to stretch open the partially blocked artery) or bypass surgery (surgical insertion of a segment of vein between the main artery or aorta and the coronary or heart artery which routes the blood flow around the blockage). UA management ultimately centers on individualization of therapy and the concept of plaque stabilization. If sufficient blood flow through the coronary arteries cannot be guaranteed with medical therapy, then coronary angiography with an eye to proceeding with coronary angioplasty or bypass surgery is warranted.
