Troponin T

Troponin T (TnT), is a protein (protein) found in muscles. The following subunits can be distinguished:

  • Inhibitory – I
  • Tropomyosin binding – T
  • Calcium binding – C

Subforms I and T can also be detected in myocardial (heart muscle) troponin forms in myocardial infarction (heart attack). Cardiac troponin I (cTnI) represents a subunit of the regulatory protein troponin and is released during cardiac (heart-related) tissue injury. An increase in troponin T can be expected after 3-8 hours after infarct onset. Sensitivity (percentage of diseased patients in whom disease is detected by use of the test, ie, a positive test result occurs) in myocardial infarction (several hours old) is 94%.The maximum is reached at 12-96 hours after infarct onset.Normalization occurs after approximately 2 weeks.

The procedure

Material needed

  • Blood serum

Preparation of the patient

  • If to detect cardiovascular risk (high-sensitivity troponin test (hs-cTnT): 48 hours before the test must avoid intense exercise and stress testing.

Confounding factors

Troponin – normal value/assessment

<0.4 μg/l
  • No evidence of recent myocardial infarction (older than 3-8 hours).
0.4-2.3 μg/l
  • Myocardial infarction not to be excluded with certainty (further increase?).
  • Suspicion of cardiomyopathy (heart muscle disease).
> 2.3 μg/l
  • Suspected myocardial infarction

Troponin T high sensitive (troponin Ths; hs-cTnT) – normal value/assessment

<14 ng/l (0.014 ng/ml/14 pg/ml)
  • Cut-off (test result is to be considered negative.
14-50 ng/l (> 0.014-0.050 ng/ml or > 14 – 50 pg/ml)
  • Gray area
> 50 ng/ml (> 0.050 ng/ml or > 50 pg/ml) are considered clearly positive
  • Positive

For the high-sensitivity troponin test (hs-cTnT), a second measurement should be performed after only 1 hour (“1-hour exclusion protocol”; ESC 0/1h rule-out/in algorithm) in case of initially inconclusive values.The recommendation for the ESC 0/3h algorithm was downgraded from class I to class IIa.

Indications

  • Suspected myocardial infarction (heart attack).
  • Investigation of cardiovascular risk (hs-cTnT measurement).

Interpretation

Interpretation of increased values

  • Amyloidosis – extracellular (“outside the cell”) deposits of amyloids (degradation-resistant proteins) that can lead to cardiomyopathy (heart muscle disease), neuropathy (peripheral nervous system disease), and hepatomegaly (liver enlargement), among other conditions.
  • Aortic dissection (synonym: aneurysm dissecans aortae) – acute splitting (dissection) of the wall layers of the aorta (aorta), with a tear of the inner layer of the vessel wall (intima) and hemorrhage between the intima and the muscle layer of the vessel wall (outer media), in the sense of an aneurysm dissecans (pathological expansion of the artery).
  • Aortic valve disease
  • Apoplexy (stroke)
  • ARDS (acute respiratory distress syndrome) – acute respiratory failure.
  • Arrhythmias (cardiac arrhythmias)
  • Extensive burns involving > 30% of the body surface area.
  • Hemochromatosis (iron storage disease).
  • Heart failure (cardiac insufficiency; in hs-cTnT or in TNT* ).
  • Hypertensive crisis* – blood pressure derailment with values > 200 mmHg.
  • Hyperthyroidism (overactive thyroid gland)
  • Hypothyroidism (hypothyroidism)
  • Unstable angina (chest tightness; heart pain) (evidence of microinfarctions).
  • Cardiomyopathy – heart muscle disease leading to impaired cardiac function.
  • Congestive heart failure, severe acute or chronic.
  • Coronary syndrome, acute – spectrum of cardiovascular disease ranging from unstable angina (UA) to the two major forms of myocardial infarction (heart attack), non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI).
  • Pulmonary embolism – occlusion of one or more pulmonary vessels by a thrombus (blood clot), usually based on thrombosis.
  • Myocardial infarction (heart attack), acute or subacute (smaller infarction, a larger infarction in the early stages)* .
  • Myocarditis* (inflammation of the heart muscle), endocarditis (inflammation of the inner lining of the heart), pericarditis (inflammation of the pericardium).
  • Renal insufficiency, acute and chronic * (due toKidney filters cardiac enzyme).
  • Perioperative myocardial injury after noncardiac surgery (MINS).
  • Pulmonary hypertension (PH; pulmonary hypertension).
  • Rhabdomyolysis – dissolution of skeletal muscle.
  • Sarcoidosis (synonyms: Boeck’s disease; Schaumann-Besnier’s disease) – systemic disease of connective tissue with granuloma formation.
  • Shock*
  • Severe acute heart failure (cardiac insufficiency).
  • Severe chronic heart failure
  • Severe pulmonary hypertension (pulmonary hypertension).
  • Sepsis (blood poisoning)
  • Scleroderma – autoimmune connective tissue disease, which is counted among the collagenoses.
  • Stress cardiomyopathy* (synonyms: Broken heart syndrome), Tako-Tsubo cardiomyopathy (Takotsubo cardiomyopathy), Tako-Tsubo cardiomyopathy (TTC), Tako-Tsubo syndrome (Takotsubo syndrome, TTS), transient left ventricular apical ballooning) – primary cardiomyopathy (myocardial disease) characterized by short-term impairment of myocardial (heart muscle) function in the presence of overall unremarkable coronary arteries; clinical symptoms: Symptoms of acute myocardial infarction (heart attack) with acute chest pain (chest pain), typical ECG changes, and increase in myocardial markers in the blood; in approx. 1-2% of patients with a suspected diagnosis of acute coronary syndrome are found to have TTC on cardiac catheterization instead of a presumed diagnosis of coronary artery disease (CAD); nearly 90% of patients affected by TTC are postmenopausal women; Increased mortality (death rate) in younger patients, especially men, largely due to increased rates of cerebral hemorrhage (brain bleeding) and epileptic seizures; possible triggers include stress, anxiety, heavy physical work, asthma attack, or gastroscopy (gastroscopy); risk factors for sudden cardiac death in TTC include: Male gender, younger age, prolonged QTc interval, apical TTS type, and acute neurological disorders.
  • Subarachnoid hemorrhage (SAB; cerebral hemorrhage).
  • Systolic heart failure (congestive heart failure; decrease in left ventricular pump function (LVEF < 50%), severe acute or chronic
  • Tachy- or bradyarrhythmias (irregular heartbeat associated with tachycardia (> 100 heartbeats per minute) or bradycardia (< 60 heartbeats per minute), respectively) – e.g., tachycardic atrial fibrillation (VHF)
  • Trauma (injury) – e.g. chest compression.
  • Condition after ablation – surgical ablation for special heart diseases such as cardiac arrhythmias, cardiomyopathy.
  • Condition after defibrillation (treatment method against the life-threatening cardiac arrhythmias ventricular fibrillation and ventricular flutter, in which the normal heart activity is to be restored by strong electric shocks).
  • Condition after endomyocardial biopsy – tissue removal from the inner layer of the heart.
  • Condition after cardioversion – electrotherapy to rhythmize the heart rhythm.
  • Condition after percutaneous coronary intervention or percutaneous coronary intervention (abbreviation PCI; synonym: percutaneous transluminal coronary angioplasty, PTCA).
  • Condition after prolonged endurance exercise – extreme sports such as marathons.
  • Burns, if they affect more than 30% of the body surface area.
  • Intoxication (poisoning) with cardiotoxins such as Adriamycin, 5-fluorouracil, Herceptin, snake venoms.

* Common diseases with troponin T levels only slightly above normal.

See COMPASS-MI (risk calculator) below.

Interpretation of lowered values

  • Not relevant to disease

Troponin determination due to suspected myocardial infarction.

  • The above threshold for troponin probably needs to be lowered for women to reduce underdiagnosis of myocardial infarction.
  • For the high-sensitivity troponin test (hs-cTnT), a second measurement should be performed as early as after 3 hours (“3-hour exclusion protocol”) in the case of initially inconclusive values.In the case of suspected NSTEMI, a second hs-troponin determination should be performed as early as after 1 hour (1-hour inclusion and exclusion algorithm).
  • COMPASS MI trial (“Calculation of Myocardial Infarction Risk Probabilities to Manage Patients with Suspicion of Myocardial Infarction”):
    • “low-risk” constellation: for example, troponin I concentration <6 ng/l at baseline and an absolute increase of less than 4 ng/l after 45 to 120 minutes (negative predictive value of second sampling was 99.5%); 0.2% of patients experienced myocardial infarction or death in this constellation in the subsequent 30 days.Compass MI (risk calculator).
  • If myocardial infarction is suspected, the following laboratory parameters should be determined:
    • Myoglobin
    • Troponin T (TnT) or cardiac troponin I (cTnI).
    • CK-MB (creatine kinase myocardial type).
    • CK (creatine kinase)
    • Aspartate aminotransferase (AST, GOT)
    • LDH (lactate dehydrogenase)
    • HBDH (hydroxybutyrate dehydrogenase)

Troponin elevation without suspected myocardial infarction.

  • Unselective use of troponin testing in the emergency department (without suspicion of acute coronary syndrome): 1 in 8 patients had an increase in hs-cTnT (esp. affected: elderly and multimorbid patients); 99.5% had no myocardial infarction.
  • Troponin elevation without myocardial infarction also indicate myocardial damage:
    • In patients with HFrEF (heart failure with reduced ejection fraction) – also called “systolic” heart failure – these are associated with an increased risk of future clinical events.
    • In patients with HFpEF (heart failure with preserved ejection fraction) – also called “diastolic” heart failure – mortality (death rate) during hospitalization (primary endpoint) was more than twice as high in the group with troponin elevation as in the group with normal troponin levels (3.95% vs. 1.84%).
  • Troponin T level is currently the most important risk factor for postoperative mortality (death rate). There are 6 days or more between the rise in the value and death in most patients (time for intervention: acetylsalicylic acid (ASA), statins).
  • Elevated troponin T levels in diabetic patients with stable angina (AP) were associated with an 85% higher cardiovascular event rate (myocardial infarction, apoplexy/stroke). There was also a highly significant difference in all-cause mortality at 5 years. With elevated troponin T, 19.6% died, compared with 7.1% with normal levels (p <0.001).
  • Troponin level has low predictive probability of coronary artery disease (CAD).
  • The high-sensitivity troponin test (hs-cTnT) compared with the calcium score (cardiac computed tomography, cardiac CT) showed in one study that hs-cTnT levels and calcium score were independently associated with increased risk of coronary artery disease (CAD). Thus, the hs-cTnT test is able to detect subclinical atherosclerosis and risks for cardiovascular disease.
  • Data from the WOSCOP study show that baseline troponin levels (hs-cTnT) are independent predictors of the occurrence of myocardial infarction (heart attack) or cardiovascular-related death. Furthermore, statins were found to cause a decrease in troponin independently of LDL cholesterol lowering.
  • Competitive sports:
    • After exhaustive endurance exercise (competitive athletes), exercise-induced troponin elevation may occur without the need for a disease-related cause. Values usually normalize within 24 hours and return to the normal range after 24 to 48 hours (maximum 72 h).
    • In participants of the Nijmegen March (30-55 km march): 9% of participants were found to have an increase in troponin I to >0.04 µg/L after the march; these participants showed a higher cardiovascular event rate than participants without a relevant troponin I increase after a follow-up period of approximately three and a half years (27% vs 7%, HR 2.48 [95% CI, 1.29-4.78]).CONCLUSION: An increase in cardiac necrosis markers after greater exercise is an early marker of increased cardiovascular risk and mortality (death rate).