Troponin elevation is not always acute coronary syndrome

Dr.

Ayman Ahmed Abdelaziz

Professor of Cardiology-Egypt

•Schematic representation of the cardiac myofibrillar thin filament. Cardiac troponins

exist in a structural (bound) form and in a free

•cytosolic pool. Cardiac troponins are released from myocytes as complexes or as free protein

Cardiac troponins exist in a structural (bound) form and in a free cytosolic pool. They are released from myocytes as complexes or as free protein

Cardiac troponins

Regulatory proteins that form the cornerstone of muscle contraction.

1. Troponin C: binds with calcium.2. Troponin T: binds with tropomyosin.3. Troponin I: inhibites contraction.

Troponin C is not cardiac specific, and thus is not used for the diagnosis of cardiac injury.

CTnT and I are specific markers of myocardial injury ACS

Cardiac troponins (T & I)

Require myocardial necrosis for release.

Early rise (3-4 hours after symptom).

Peak 12-24 hours.

Continuous release up to 10-14 days.

Definition of MI

Detection of rise and/or fall of cardiac biomarkers (preferably troponin) above the 99th percentile of

the upper reference limit + with evidence of

ischaemia with at least one of the following:

Ischaemic symptoms

ECG changes of new ischaemia, development of pathologic Q-waves in the ECG or

Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality.

Peri-procedural myocardial infarction

Post PCI MI: three-fold increase from the normal baseline value.

Post CABG: a five-fold increase from the baseline during 1st 72 hours, along with associated findings, such as new Q waves.

After non-cardiac surgery: The same cut-off levels used to diagnose an acute MI should be used to detect perioperative injury.

Post PCI

MI occurring after PCI (subtype 4a) , as an increase cardiac troponins >3 × the upper reference limit (URL)

5% to 40% of cases, even when the procedure seems successful and uncomplicated

How do troponin compare with

ECG in ACS?

Troponin and EKG changes complementary.

Differentiating the diagnosis of unstable angina and non-ST elevation myocardial infarction

Negative troponin + normal EKG: mortality 1%.

Negative troponin + ischemic EKG: mortality 4% at 1 month.

TIMI score

1. Age 65 years.

2. 3 risk factors for CAD.

3. Coronary stenosis 50%.

4. ASA use in past 7 days.

5. Severe angina 24 hours

6. + cardiac markers.

7. ST deviation 0.5 mm.

Intermediate:3-4 (14-days events:13-20%).

High: 6-7 (14-days events: 40%).

System Causes of Troponin Elevation

Cardiovascular Acute aortic dissection

Arrhythmia

Medical ICU patients

Hypotension

Heart failure

Apical ballooning syndrome

Cardiac inflammation

• Endocarditis, myocarditis, pericarditis

Hypertension

Infiltrative disease

• Amyloidosis, sarcoidosis, hemochromatosis,

Sclerodermia

Left ventricular hypertrophy

Myocardial Injury

Blunt chest trauma

Cardiac surgeries

Cardiac procedures

• Ablation, cardioversion, percutaneous intervention

Chemotherapy

Hypersensitivity drug reactions

RespiratoryAcute PE

ARDS

Infectious/Immune

Sepsis

Viral illness

Thrombotic thrombocytopenic purpura

Gastrointestinal Severe GI bleeding

Nervous system

Acute stroke

• Ischemic stroke

• Hemorrhagic stroke

Head trauma

Renal Chronic kidney disease

EndocrineDiabetes

Hypothyroidism

Musculoskeletal Rhabdomyolysis

Integumentary Extensive skin burns

Troponins and heart failure

May have chronic elevation of both TnT and TnI.

Diagnosis of ACS require serial measurement.

As low as TnT<0.05 predicts increased risk.

Tn in stable ambulatory HF patients

136 stable HF patients, LVEF <35%, NYHA II-IV

TnT was elevated at baseline in 24%

Causes of Tn release in HF

Type I myocardial infarction

Reduced oxygen supply ( anemia, hypotension)

Increased oxygen demand

Coronary ischemia

Elevation of Tn in a patient with HF should always be interpreted in

the context of Type I MI, especially in the setting of significant rise or

fall of the marker

Type II myocardial infarction

Increased transmural wall stress

Elevated filling pressures

Dilated LV chamber size

Lower tissue perfusion

Stiffer myocardium

Januzzi, et al. Eur Heart J 2012; 33: 2265-71

Cardiac-specific causes of Tn release in HF

Mechanisms other than Type I or II MI

Direct toxicity of circulating neurohormones

Infiltrative processes (amyloidosis etc.)

Toxic exposures (e.g. Alcohol or chemotherapy agents)

Inflammation (myocarditis)

Cardiomyocyte apoptosis or autophagy (wall stretch)

Normal (or abnormal) cardiomyocyte turnover

Stress cardiomyopathy

Tachycardia-induced cardiomyopathy

Pericarditis and myocarditis

32–49% of cases of acute pericarditisReflect myocardial lesion (myopericarditis)Myopericarditis: young, recent fever + GIT symptoms

and/or skeletal muscle myalgia + ST-segment elevation at presentation.

Troponin increase: Extent of myocardial inflammation, but unlike ACS it does not seem to carry an adverse prognosis.

Magnetic resonance imaging (MRI) : diagnostic (delayed enhancement usually involves the subendocardial layer in MI, while it spares the subendocardial layer in myocarditis)

Tako-tsubo (Stress-induced cardiomyopathy)

Older woman with an acute emotional or physiologic stress.

Involvement of apical and/or mid LV with sparing of basal segments.

Modest rise in cTn that peaks within 24 h.

The magnitude of increase in the biomarkers is less than that observed with a STEMI and disproportionately low for the extensive acute regional wall motion abnormalities

Acute pulmonary embolism

High risk PE (PE and shock/ hypotension)

Thrombolytic therapy or embolectomy

Intermediate-risk PE are characterized as patients with a stable circulation but with RV dysfunction or elevated Troponins

Increased cTn values were associated with a higher mortality in the haemodynamically stable patients

Normal echocardiogram + negative cTnI level was most useful to identify patients at lowest risk for early death

Pulmonary embolism

Positive cTnI: correlated with having more segmental defects on ventilation–perfusion scintigraphy.

Causes of elevated troponin in PE : Acute right ventricular strainsHypoxaemia due to perfusion–ventilation

mismatchhypoperfusion as a consequence of low output

and reduced coronary blood flowParadoxical embolism from systemic veins to the

coronary arteries, usually via a PFO.

Troponin in aortic dissection

• CTn is elevated in up to 18% of pts with AAD, indicative of the high acuity of illness than specific to aortic dissection itself.

• Misdiagnosis of AAD may result in incorrect administration of anticoagulation therapy.

Tachycardias

Prolonged episodes of supraventricular tacharrhythmias (SVT)

Shortening of diastole with subsequent subendocardial Ischaemia

Troponin T and renal failure

Chronic elevation.

Not related with frequency and efficacy of dialysis or creatinine level.

Specificity of cTn for ACS is lower compared with pts without renal disease.

CKD patients who present with signs and symptoms suspicious for AMI, a change in troponin concentration (ie, rise or fall over three to six hours after presentation) should be used to define AMI, rather than a single value on presentation.

20 % change in serially measured troponins

Acute illness

Coronary ischemia in the absence of plaque rupture or coronary thrombosis : supply-demand mismatch ( Type II MI).

Severe disease : microvascular dysfunction and myocytotoxiceffects of endotoxin, cytokines, reactive oxygen radicals.

50% of patients with severe sepsis and septic shock may develop impairment of ventricular performance. Elevations in cTncorrelate with the presence of LV systolic dysfunction.

Elevated cTn predicts mortality

Snake or scorpion bitesmyocardial injury by biologic toxins, vasospasm and coagulation abnormalities.

Other Causes

Troponin increases can reach levels typically diagnostic for acute MI.

Less marathon experience and younger age. Muscular fatigue Transiently decreased systolic and diastolic

function (cardiac fatigue) Right ventricular injury Degradation of ‘cytosolic’ troponin or increased

permeability of the cell membranes of myocytes under stress.

Cardiac troponin increases among runners in the Marathon

Cardiac contusion

• Thoracic trauma

• Patient with chest trauma and an absence of other injuries or haemodynamic instability, with normal ECG and cTn can be discharged

• Increased cTn may serve to identify patients at increased risk of mortality

False Positive

• Rarely, elevated troponin concentrations cannot be explained despite thorough clinical examination.

• Related to: heterophilic antibodies, and analyzer malfunction

Relation between troponin level and possible causes

Conclusion

Cardiac troponins (cTn) are the most sensitive and specific biochemical markers of myocardial injury and with the new high-sensitivity troponin methods very minor damages on the heart muscle can be detected.

Elevated cTn levels indicate cardiac injury, but do not define the cause of the injury.

Cardiac troponin elevations are common in many disease states and do not necessarily indicate the presence ACS.

Stable cTn values without significant dynamic changes are likely markers of chronic structural heart disease.

Elevated troponins have a strong correlation with adverse cardiovascular outcome whether CAD is present or not.