Troponin leaks due to neurogenic causes
Other causes of myocardial injury with the presence of detectable troponin in the bloodstream of note are neurogenic in nature. A stroke or any type of brain hemorrhage compromises the body’s neurologic system to regulate normal autonomic function.11,12 The heart rate and the cardiac conduction system are primarily regulated by the autonomic system; thus, changes in brain function affect cardiac function, leading to dysfunctional rates or rhythms.12 These effects may lead to myocardial injury, causing detectable cardiac troponin levels. While a syncopal episode can be due to a brain injury or a direct cardiac injury, both however, can lead to troponin leak and need to be differentiated with further diagnostic testing.
Chronic elevation of troponins
In patients with chronic renal failure, cardiac troponin, specifically troponin T, is elevated at baseline and directly correlates with the severity of renal disease. The exact cause of this chronic elevation is not entirely understood.13 Some explanations include a subclinical myocardial injury, an inflammatory response in renal failure, or a chronic volume overload. Chronic renal insufficiency may possibly cause microinfarcts in the myocardium, leading to low levels of troponin leaks.14,15 Moreover, troponin T is considered to be elevated due to poor renal clearance in chronic renal insufficiency.16 A few studies have shown that the baseline level of cardiac troponin in renal failure may be used to determine prognosis of disease progression and mortality.17,18 Thus, when presented with an elevated troponin in a patient with renal failure, it is helpful to obtain serial troponin levels when a concern for ACS is raised. It is important to follow the trends of troponin to determine whether elevated troponin levels are in line with a chronically elevated baseline, or whether such an elevation is caused by an insult or mechanism, such as ACS, where a typical rise and fall of the troponin in the bloodstream will be seen.
Sepsis and the ICU setting
Septic shock leads to systemic inflammation, which causes changes in the myocyte membrane permeability and may lead to a leak of cardiac troponin markers into the bloodstream.19 Systemic inflammation and metabolic processes by itself may cause right and left ventricular dysfunction, which may lead to further myocyte injury.20 This process is, however, reversible with resolution of sepsis. Thus, management includes maintaining systemic pressure and organ perfusion until sepsis resolves.21
Other conditions causing troponin elevations
Transient hypotension and limited ventricular reserve, as in cases of decompensated heart failure, lead to strain on the diseased myocardial cells and can result in troponin elevation.22,23 As myocardial cells are already in a diseased state secondary to a chronic decrease in blood supply, they may have greater difficulty in maintaining the integrity of the cell membrane.
GUIDELINES FOR DIAGNOSING ACS
Troponin elevation is truly a marker for myocardial injury but not necessarily for diagnosing an episode of ACS or an acute MI. Guidelines on diagnosing an acute MI need to be followed and considered in all cases where there is a troponin rise and clinical evidence suggesting ACS.
In 2000, the European Society of Cardiology and American College of Cardiology published a consensus statement on the diagnosis of MI.24These criteria include a typical rise and gradual fall in troponin levels or a rapid rise and fall in creatinine kinasemuscle brain biomarkers with at least 1 of the following:
• Ischemic symptoms
• Development of pathologic Q waves on ECG
• ST segment changes on ECG
• Imaging evidence of new loss of myocardium or new wall motion abnormality
In 2007, the Joint Task Force of the European Society of Cardiology, the American College of Cardiology Foundation, the American Heart Association, and the World Health Organization again revised the criteria for an acute MI. In this update, an acute MI is defined as the death of cardiac myocytes secondary to ischemia.1 Since cardiac troponin levels are sensitive enough to detect even minute injury to the myocardial tissue, the criteria for ACS and of MI take into account the amount of myocardial cell loss, circumstances leading up to the infarction, and the timing of observing the infarction leading to a differential classification.24 The most up-to-date classification system for the causes of MI is described by Thygesen and colleagues in their article “Universal Definition of Myocardial Infarction,” in the journal Circulation in 2007.3
Hence, a purist may classify cases of myocardial injury that occur from decreased supply of oxygen and nutrients to the cells, or increased demand from the cells itself, as type 2 MI. Thus, many of the non-ACS causes of troponin leak can be classified under a type 2 MI, whereas true ACS would be a type 1 MI. This classification system is now standardized and provides a better classification for MI than the previous traditional classification of STEMI vs NSTEMI. The underlying etiology of these type 2 infarctions needs to be treated, as some of these troponin leaks are due to increased demand or changes in cell permeability. Not treating the underlying conditions may lead to misdiagnosis and failure to treat the patient.
Patients with underlying chronic conditions (eg, CHF, COPD, and HTN) are prone to frequent troponin leaks with a slight rise in BP, heart rate, or blood volume. Such patients must be evaluated clinically and treated for their underlying conditions as well as CAD, if present. Troponin biomarkers are thus a sensitive marker for myocardial strain and damage and need to be used to rule out any myocardial damage, not ACS. Due to its high sensitivity, cardiac troponin levels are now used more as a test to rule out ACS than to rule it in.