Etiologies of Troponin Elevation

Acute Aortic Syndrome

IschemiaHemodynamic stressacute injury

This cause is not itemized in Tables 2 or 3 of the 5th UDMI; the mechanism tags are our own classification.

Epidemiology

In a meta-analysis of four studies and 496 patients with acute aortic dissection (AAD), predominantly type A, elevated Tn measured by conventional assays was present in 26.8% of patients with AAD and ranged between 23% and 33% in individual studies . Meanwhile, in a study that made use of hs-Tn assays, elevated hs-TnT was seen in 61.2% of patients who presented with type A aortic dissection .

Hypothesized Mechanism

The aortic wall contains the calcium-binding protein calponin but not Tn , suggesting that the mechanism of Tn release in AAD is likely multifactorial and may include coronary artery obstruction, acute LV pressure overload, and shock. A study of 398 patients with AAD found that the presence of Tn elevation (both conventional and hs-Tn) during AAD was frequently associated with ACS-like ECG abnormalities, with 13% of patients with abnormal Tn presenting with classic ST elevation . Among 10 patients who underwent transesophageal echocardiograms, 4 had an anatomic obstruction of at least one coronary artery due to coronary dissection or diastolic apposition of the flap to the ostium, illustrating at least one mechanism of myocardial ischemia and likely consequent Tn release .

Prognostic Implications

The association of elevated Tn with mortality in aortic dissection is unclear. In the aforementioned study, the combination of Tn elevation and ACS-like ECG findings was associated with a two-fold increased risk of in-hospital diagnostic delay and a significantly increased risk of the composite endpoint of coronary angiography, antithrombotic therapy, or in-hospital diagnostic delay. Nevertheless, the in-hospital diagnostic delay did not influence mortality . In contrast, a meta-analysis of five studies and 711 patients and a study of 103 patients with type-A AAD showed an association between Tn elevation (conventional or hs-Tn) and short-term mortality .

Sources:

Mechanisms of myocardial injury

Ischemia is only one of the ways troponin rises. These are the mechanisms the 5th UDMI recognizes for acute and chronic injury.

Mechanisms of acute myocardial injury

Mechanism	Conditions
Ischemia	Myocardial infarction
Inflammation	Myocarditis (autoimmune, infectious, toxic) Heart transplant rejection Cytokine-mediated injury in sepsis
Hemodynamic stress	Supply–demand imbalance* Tachy- or bradyarrhythmia Acute heart failure Acute pulmonary embolism Malignant hypertension
Physiological stress	Strenuous exercise
Catecholamine stress	Takotsubo syndrome Subarachnoid hemorrhage Stroke Epileptic seizures Pheochromocytoma
Toxicity	Anthracyclines ErbB-targeted therapies Tyrosine kinase inhibitors Immune checkpoint inhibitors Radiation
Trauma	Electrical cardioversion Percutaneous coronary or structural intervention Catheter ablation or device implantation Cardiac surgery Cardiac contusion

*Any acute condition that causes oxygen imbalance with reduced supply (hypoxia, anemia, hypotension) and/or increased demand (tachycardia, hypertension).

Mechanisms of chronic myocardial injury

Mechanism	Conditions
Ischemia	Chronic coronary syndrome Ischemic cardiomyopathy
Other cardiomyopathies	Hypertrophic Hypertensive Dilated Chronic inflammatory Restrictive Infiltrative Uremic cardiomyopathy in chronic kidney disease
Hemodynamic stress	Chronic heart failure Systemic hypertension Pulmonary hypertension
Structural	Valvular heart disease Congenital heart disease Cardiac tumor

Interference checklist: does this troponin fit?

Not every raised troponin is myocardial injury. Antibody-mediated interference and macrotroponin may account for as many as 1 in 2 elevated troponin I values in asymptomatic populations, so work through these clues when the result does not make sense .

The troponin does not fit the clinical pictureThe 5th UDMI says to suspect interference when an elevated value is not consistent with the clinical findings.
Values go up and down with no coherent pattern on serial testingA real rise and fall follows the kinetics of injury; an erratic pattern makes interference more likely.
Troponin I and T disagree, or two troponin I assays disagreeMeasuring on an alternative immunoassay identifies interference, and discordance is strongly suggestive.
Persistently high for weeks with no cause foundMacrotroponin (troponin bound to immunoglobulin) clears slowly, with a half-life of several weeks, and can keep levels high without acute or chronic injury.
Heterophilic antibodies are possibleThey can cause false-positive results ex vivo, although with most current assays this is an uncommon cause.
Biotin supplementation, or a hemolyzed sampleHemolysis and biotin can reduce the measured troponin, so a low result may be falsely reassuring.
Fibrin micro-clots or a poorly processed sampleFibrin micro-clots can increase the measured troponin.
Point-of-care assay on whole bloodAnalytical performance at the point of care can be more variable in whole blood than on plasma or serum in a central laboratory.

Tick any clue that applies. Nothing ticked yet.

How immunoassay interference works (figure)

Mechanisms of false-positive and false-negative troponin immunoassay results — (A) Standard detection: a capture antibody and a labeled detecting antibody sandwich the troponin. (B) False positives: a heterophilic or auto-antibody bridges the two antibodies with no troponin present (left), or macrotroponin, a troponin-immunoglobulin complex, is measured as troponin (right). (C) False negatives: a heterophilic or auto-antibody blocks the capture antibody (left) or the detecting antibody (right).

Causes of troponin elevation