Troponin elevation is not always acute coronary syndrome

1. Troponin elevation is not always
acute coronary syndrome
Dr.
Ayman Ahmed Abdelaziz
Professor of Cardiology-Egypt

2. •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

3. 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

4. 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.

5. 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.

7. 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.

8. 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

9. 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.

10. 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%).

11. 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

12. Respiratory
Acute 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
Endocrine
Diabetes
Hypothyroidism
Musculoskeletal Rhabdomyolysis
Integumentary Extensive skin burns

13. 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.

14. Tn in stable ambulatory HF patients
136 stable HF patients, LVEF <35%, NYHA II-IV
TnT was elevated at baseline in 24%

15. 

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

16. 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

17. Pericarditis and myocarditis
32–49% of cases of acute pericarditis
Reflect 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)

18. 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

19. 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

20. Pulmonary embolism
Positive cTnI: correlated with having more
segmental defects on ventilation–perfusion
scintigraphy.
Causes of elevated troponin in PE :
Acute right ventricular strains
Hypoxaemia due to perfusion–ventilation
mismatch
hypoperfusion as a consequence of low output
and reduced coronary blood flow
Paradoxical embolism from systemic veins to the
coronary arteries, usually via a PFO.

21. 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.

22. Tachycardias
Prolonged episodes of supraventricular
tacharrhythmias (SVT)
Shortening of diastole with subsequent
subendocardial Ischaemia

23. 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

24. Acute illness
 Coronary ischemia in the absence of plaque rupture or coronary
thrombosis : supply-demand mismatch ( Type II MI).
 Severe disease : microvascular dysfunction and myocytotoxic
effects of endotoxin, cytokines, reactive oxygen radicals.
 50% of patients with severe sepsis and septic shock may develop
impairment of ventricular performance. Elevations in cTn
correlate with the presence of LV systolic dysfunction.
 Elevated cTn predicts mortality

25.  Snake or scorpion bites
myocardial injury by biologic toxins, vasospasm
and coagulation abnormalities.
Other Causes

26.  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

27. 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

28. False Positive
• Rarely, elevated troponin concentrations
cannot be explained despite thorough clinical
examination.
• Related to: heterophilic antibodies, and
analyzer malfunction

29. Relation between troponin level and
possible causes

30. 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.