Those curious cardiac enzymes

15 May

by Carolyn Thomas

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 (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 presenting with cardiac symptoms were seven times more likely to be misdiagnosed and sent home from Emergency compared to their male counterparts.*

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 troponinparticularly 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.

Many patients who have had a heart attack have increased troponin levels within six hours following the onset of symptoms. According to a 2006 report* 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** 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”.

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* 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.

♥  See also:

k

* 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.

** 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

11 Responses to “Those curious cardiac enzymes”

  1. Delana Rangitsch July 31, 2012 at 4:28 am #

    Blood tests can reveal the overall health of your body, therefore, it is necessary to get a blood test at least once a year. ..*;.

    Warm regards

    Like

  2. Mary May 16, 2012 at 8:52 am #

    Carolyn,

    A physician told me that hospital protocols can vary. At her hospital, troponins are drawn 3 times, every 8 hours. At the minimum, troponins should be done twice from 6 to 8 hours apart. This gives an opportunity to see if there are rising values. Now that I know this, I would insist on the 2 or 3 times protocol.

    ERs have a “person can only be in the ER 23 hours” by insurance. Anything more requires hospital admission. This may drive the “get em out” quickly if the person looks like they don’t fit the profile.

    I will add as well, that patients are also eager to leave, as lying in an ER for 23 hours is tedious, hard to sleep and certainly no TV to while away the hours. It’s an ordeal. That may drive the patients to choose to leave prematurely, particularly if they are being told they “probably” don’t have an MI problem, and instead it’s GI or anxiety. This also makes it hard for the patient to return (emotionally speaking) and worried about being perceived as imagining things.

    All in all, it’s a complicated decision – but it shouldn’t be.

    Best,
    Mary

    Like

    • Carolyn Thomas May 16, 2012 at 1:58 pm #

      Hi Mary – all excellent points. That’s quite the variation in E.R. protocol, isn’t it? A common practice, I’ve been told, is to do cardiac enzyme blood tests at 4 and 6 hours after admission. Or 3x q8h. Or 2x 6 and 8 hours after admission. Good grief….

      Like

  3. Deborah Walker May 15, 2012 at 8:25 am #

    How do you pronounce “troponin”? I’m not kidding – I want to know! If I’m going to meet up with the “pat on the head and send home” syndrome, I’ll need to be able to demand the right thing.

    Thanks again for all you do, Carolyn.

    Like

    • Carolyn Thomas May 15, 2012 at 10:11 am #

      Hi Deborah – it’s trōp’-ə-nin or sometimes trō-pō’-nin.
      cheers,
      C.

      Like

  4. Dina May 15, 2012 at 7:42 am #

    There’s a confusing message in that time is heart muscle and that clarity of diagnosis takes time when the EKG and other earlier signs are within normal. Once again the importance of advocating for oneself to know that there needs to be follow up testing/observation for women as well as men.

    Thanks for providing the rationale for those with concerns to insist on necessary observation. You are an advocate through cyberspace who provides us with ways to advocate for ourselves.

    Like

    • Carolyn Thomas May 15, 2012 at 7:50 am #

      Thank you for your comment, Dina. You raise an important point. For example, had I known more about these blood tests at the time, I could have requested a follow-up test later that day. Staff could have actually discharged me and just had me return later – no need to even take up a bed in the E.R all day! Anything would have been better than sending a patient presenting with textbook heart attack symptoms home with a GERD misdiagnosis.

      Like

  5. holly May 15, 2012 at 7:36 am #

    Thanks for the easy to understand explanation of cardiac enzymes!

    Like

    • Carolyn Thomas May 15, 2012 at 7:40 am #

      You’re welcome, Holly.

      Like

  6. RehabilitateYourHeart May 15, 2012 at 5:26 am #

    Great article!

    Like

    • Carolyn Thomas May 15, 2012 at 5:53 am #

      Glad you liked it. :-)

      Like

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