When I showed up in the Emergency Department with textbook heart attack symptoms – chest pain, nausea, sweating, and pain radiating down my left arm – the hospital staff snapped to work and immediately ordered a flurry of tests. These included an EKG, blood tests, chest x-ray and a treadmill stress test. But all test results came back “normal”. I was then told that I was in the “right demographic” for acid reflux before being sent home – less than five hours after the onset of symptoms.
I left hospital that morning feeling terribly embarrassed for having made such a fuss over just a little case of indigestion. It was only much later – after finally being correctly diagnosed, taken directly from the E.R. to O.R. and admitted to the cardiac care unit for a myocardial infarction (MI or heart attack) caused by a fully occluded Left Anterior Descending coronary artery – when I learned that my “normal” blood tests may have been “normal” that day because I had been sent home too soon.
This is the part of my story where I like to repeat another story – this one told to me by a woman in one of my heart health presentation audiences recently. She described being an E.R. patient herself, and overhearing a conversation between the E.R. physician and the (male) patient lying in the bed next to her, behind the cubicle curtain. She heard the doctor telling the (male) patient:
“Your EKG is fine, and your blood tests are fine, too. But we’re going to keep you for observation just to make sure it isn’t your heart.”
Thus yet another male patient with symptoms but inconclusive cardiac test results is kept in hospital for observation, while I and countless other females with symptoms but inconclusive cardiac test results are misdiagnosed, patted on the head, and sent home from the E.R.
Turns out we’re not alone. A study published in The New England Journal of Medicine found that women in their 50s or younger presenting with cardiac symptoms were seven times more likely to be misdiagnosed and sent home from Emergency compared to their male counterparts.(1)
Here’s why that’s an important issue. The blood tests mentioned look for cardiac enzymes in the bloodstream. This test will usually be ordered when a person like me with a suspected heart attack first comes into the Emergency Department. The blood test is usually repeated two more times over the next 12 hours.
One of these tests is for a specific cardiac biomarker called troponin – particularly one called troponin I. Doctors like testing for cardiac troponin I because it’s very sensitive in detecting heart muscle damage that occurs during a myocardial infarction. The more severe the heart attack, the higher the blood levels of the troponins will be. Carolyn’s NOTE: although some consider the presence of this biomarker to be uniquely heart attack-related, increased blood concentrations of troponin are also sometimes detected in non-cardiac conditions (e.g. sepsis, hypovolemia, pulmonary embolism, or renal failure).
Patients who receive CPR, external defibrillation or shocks from an implantable cardioverter defibrillator may also have elevated troponin levels due to damage to the heart’s ventricular muscle. Medications and chemicals that called “cardiotoxic” may also elevate troponins. Such agents include some chemotherapy drugs and chemicals such as carbon monoxide.
Some marathon runners or other extreme endurance athletes are even known to have temporarily detectable troponin levels in their blood. As Dr. Malissa Wood explained in a Runner’s World interview, this is because their cell membranes may leak troponin, which is what cardiac muscle does when under extreme stress. Dr. Wood (who is the co-director of the Women’s Health Heart Center at Massachusetts General Hospital, teaches at Harvard, and has run many marathons herself), cites studies showing that the healthy heart (unlike the unhealthy heart in the throes of myocardial infarction – heart attack) can quickly repair these cell membranes, stem the troponin leakage, and suffer no permanent damage.
Many patients who experience a heart attack have increased troponin levels within six hours following the onset of symptoms. According to a 2006 report(2) in the journal, Annals of Emergency Medicine:
“If the time of symptom onset is unknown, unreliable, or more consistent with pre-infarctional angina, then time of symptom onset should be referenced to the time of Emergency Department presentation.
“No single serum marker used alone has sufficient sensitivity or specificity to reliably identify or exclude acute myocardial infarction (heart attack) within 6 hours after symptom onset.
“The serial measurements of the cardiac troponins over an 8 to 12 hour period of observation is supported by several studies as a reliable method of identifying and excluding acute myocardial infarction.
“When measured from time of symptom onset, sensitivities of the troponins for acute myocardial infarction improve in an incremental fashion and exceed 90% by 8 hours of symptom onset and approach 100% by 12 hours.”
This means that after 12 hours, almost everyone who has had a heart attack will exhibit raised troponin levels. It also means that under six hours is not long enough in most cases to identify or exclude heart attack.
Troponin I has two notable peaks, initially peaking between 15-24 hours after an MI, and then hitting a lower peak after about 6o-80 hours. Troponin levels may also remain high for up to two weeks after a heart attack strikes.
Cardiac troponin levels are normally so low they cannot be detected with most blood tests, so when they are detected, it’s usually significant in showing that heart muscle damage due to a myocardial infarction has indeed occurred. Test results are considered normal if the results are:
- Troponin I : less than 10 µg/L
- Troponin T : 0–0.1 µg/L
Normal troponin results at 12 hours after the onset of symptoms typically mean that a heart attack is unlikely.
But I was already back home from the Emergency Department within five hours – several hours before that initial 15-24 hour troponin I level would have peaked. No wonder it was “normal”.
Troponin is a complex of three proteins, two of which have particular importance in detecting heart muscle damage: troponin I and troponin T. These proteins are released into the bloodstream when the heart muscle has been damaged, typically during a heart attack. The more damage there is to the heart, the greater the amount of troponin I and T there will be in the blood.
Troponin I is thought to be a far more specific marker of cardiac damage than troponin T. Cardiac troponin T levels rise 2-6 hours after the MI and remain elevated. Both proteins return to the normal range about seven days after a heart attack.
In 2006, the European Society of Cardiology and American College of Cardiology redefined acute myocardial infarction to be predicated on the finding of increased concentrations of cardiac troponin; these and other clinical practice guidelines have led to a steady decline in the use of other cardiac enzyme blood tests like CK-MB and myoglobin as diagnostic tools to identify cardiac markers during heart attack.
Here’s a crash course in other types of blood tests for cardiac enzymes:
CK (Creatine kinase) – This is an enzyme that’s also considered to be a sensitive and specific marker for myocardial infarction, particularly in what’s known as its CK-MB form. Its value changes in 3-4 hours after an MI, peaking in 10–24 hours. The normal value is restored within 72 hours. Because of this short duration, CK testing cannot be used for late diagnosis of acute MI. And CK-MB levels can also rise in conditions like renal failure or skeletal muscle damage such as in muscular dystrophy or a crush injury, so cannot definitively identify heart attack.
Myoglobin – Levels of the biomarker myoglobin start to rise within 2-3 hours of a heart attack or other muscle injury, reach their highest levels within 8-12 hours, and generally fall back to normal within one day. An increase in myoglobin is detectable sooner than troponin, but like CK, it is not as specific for heart damage. Blood levels of myoglobin, for example, can rise very quickly with severe muscle injury or kidney damage.
AST (Aspartate transaminase) – AST appears in the heart, liver, skeletal muscles, kidneys, pancreas, and to a lesser extent in red blood cells. A high correlation exists between MI and elevated AST levels, but this enzyme also has what’s known as low organ specificity. Translated into English, this means that the test doesn’t differentiate between high AST caused by acute MI and the liver congestion caused by strenuous exercise or muscle damage caused by intramuscular injections which can also raise AST. For example, a study(3) reported in the American Journal of Clinical Pathology tested for cardiac enzymes of runners competing in the 2001 Boston Marathon and found “a statistically significant increase in the values for AST” in over 30% of the marathoners tested immediately after the race ended, then four hours later and again after 24 hours post-run. This elevation was blamed on “leakage from skeletal muscle”.
(1) Pope JH, Aufderheide TP, Ruthazer R, et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med. 2000;342:1163-1170.
(2) Fesmire et al. “Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients with Non–ST-Segment Elevation Acute Coronary Syndromes.” Annals of Emergency Medicine. Volume 48, No. 3. September 2006.
(3) AKratz et al. “Effect of Marathon Running on Hematologic and Biochemical Laboratory Parameters, Including Cardiac Markers”. Am J Clin Pathol 2002;118:856-863 © American Society for Clinical Pathology 856 DOI: 10.1092/14TY2TDJ1X0Y1V6V
♥ See also:
- Heart attack Misdiagnosis in Women
- When Your “Significant EKG Changes” are Missed
- Stress Test vs Flipping a Coin: Which is More Accurate?
- Misdiagnosis: the Perils of “Unwarranted Certainty”
- Seven Ways to Misdiagnose a Heart Attack
- The ’18 Second Rule’: Why Your Doctor Missed Your Heart Disease Diagnosis
- How Women Can Have Heart Attacks Without Having Any Blocked Arteries