Using Cardiac Biomarkers in Clinical Practice

Darcy Adin, DVM, DACVIM | UF College of Veterinary Medicine | Published: Issue 2 2024

Tags:

Editor's Pick

Cardiac biomarkers are increasingly being used to screen dogs and cats for heart disease and can add information regarding severity, prognosis, and response to treatment.  

Cardiac biomarkers are substances that can be measured as indicators of normal biological processes, pathogenic processes, or a response to therapeutic intervention. The most studied cardiac biomarkers in veterinary cardiology are cardiac troponin I (cTnI) and NT-proBNP. These biomarkers can supplement current diagnostic testing for cardiac disease or can be useful in some clinical situations, such as screening tests. It is important to recognize that these are not stand-alone tests, and when abnormal, they should prompt further investigation into the possibility of heart disease. 

B-type natriuretic peptide (BNP)

B-type natriuretic peptide (BNP) is released from the ventricles in response to stretch or stress. With cardiac disease, the proportion of BNP released from the ventricles increases and the amount released is proportional to disease severity. It is released as a prohormone that is cleaved to an active component C-BNP and an inactive component NT-proBNP. The active C-BNP mediates vasodilation and diuresis but has a very short half-life, making it a poor target for assay detection. The inactive portion NT-proBNP has a longer half-life and is the target for current diagnostic testing.

Studies evaluating NT-proBNP have generated values that are useful in specific clinical situations, and it is important to interpret any given NT-proBNP concentration in light of the signalment and clinical question to be answered. Based on studies in small breed dogs with heart murmurs, an NT-proBNP concentration of >900 pmol/L (Idexx) is suggestive of heart disease and echocardiography is recommended. In dogs with established mitral valve disease, a value >1500 pmol/L (Idexx) is suggestive of impending congestive heart failure in the next six to 12 months and warrants close monitoring of the patient.  

Various studies in Dobermans have suggested a lower cutoff value for the detection and prediction of DCM in Dobermans (Idexx cutoff is >735 pmol/L). NT-proBNP is most accurate for this purpose when combined with Holter monitoring.  NT-proBNP has also been evaluated for its ability to differentiate cardiac from respiratory causes of dyspnea. A value <900 pmol/L in a dyspneic dog suggests CHF is unlikely while a value >1800 pmol/L suggests CHF is likely. 

Furthermore, a value < 270 pmol/L in a dyspneic cat suggests CHF is unlikely, while a value >270 pmol/L is supportive of CHF as the cause of dyspnea. NT-proBNP has also been evaluated in asymptomatic cats at risk for heart disease (e.g. murmur present) and various studies support a cutoff of 100 pmol/L for the detection of heart disease in this population.  A snap NT-proBNP test is available from IDEXX. For this test, a snap negative correlates with a value <100pmol/L, and a snap positive correlates with >270 pmol/L. 

Because there is a “grey zone” with this test, it can be viewed as useful for ruling out moderate to severe heart disease (if the snap is negative) and for detecting moderate to severe heart disease (if the snap is positive); however, it may miss cats with mild heart disease (false snap negative). It is critical that the clinician interpret the NT-proBNP results considering the clinical question to be answered as well as other diagnostic testing. 

Indiscriminate testing of animals not at risk for heart disease would be expected to result in a higher false positive rate than has been reported in studies that targeted animals at risk for heart disease. In most situations, a positive test result should prompt an echocardiogram and sometimes thoracic radiographs, blood pressure, and bloodwork as part of further evaluation. Future studies will likely be aimed at determining how NT-proBNP can help guide therapy initiation and monitor response to therapy.  

Cardiac Troponin I (cTnI)

Cardiac troponin I (cTnI) is an intramyocardial protein that, when detectable in the bloodstream, indicates myocardial cell injury or death. As such, it is a nonspecific finding that can be associated with many causes of myocardial cell injury including myocardial infarction, myocarditis, cardiomyopathy, congenital heart disease, chronic valve disease, and systemic diseases affecting the heart (e.g. hyperthyroidism, GDV, anemia, toxicities, infections, brachycephalic syndrome, trauma, hypoxia, and renal failure). 

The degree of cTnI elevation parallels the extent of myocardial injury and so it can be useful for prognostication. After a single insult, troponin is released within hours, peaks around 24 hours and returns to baseline by two weeks through renal clearance. Serial evaluation, therefore, helps to separate acute from ongoing injury.  

Several studies have evaluated cardiac troponin I in dogs and cats with various heart diseases. Low-level elevations (up to approximately 2 ng/ml) are common with congenital and acquired heart disease while massive elevations seem to be most consistent with myocardial infarction or myocarditis. Troponin analysis may have prognostic benefits in some conditions. Troponin was found to be elevated in the majority of dogs with GDV and the value was related to both severity of ECG changes and survival.

Another study found elevated troponin in about half of dogs with motor vehicular trauma and ECG abnormalities in about one-third of these dogs. Cardiac troponin I has also been found to be elevated in dogs before and after cardiac pacing, with a possible myocarditis association. In critically ill ICU patients with no detectable heart disease, troponin elevations were predictive of short-term death. 

These studies, among others, highlight that cardiac injury occurs with both cardiac and extracardiac disease and that it can be an important contributor to prognosis.  We currently consider cardiac troponin I testing for patients with arrhythmias, especially when the patient is not from a breed known to have a genetically based cardiomyopathy (i.e. a myocarditis screen) and when acute ST segment changes are noted on the ECG. We also use troponin evaluation as part of screening tests for dilated cardiomyopathy and hypertrophic cardiomyopathy with other tests including echocardiography.  

We encourage other services within our hospital to consider troponin testing in critically ill patients with GDV, motor vehicular trauma, or other systemic diseases with potential for cardiac involvement. Analyzers capable of detecting lower troponin values (high sensitivity cTnI analyzers) are also available and results suggest prognostic information can be gained in dogs with degenerative mitral valve disease and other conditions. This has also been demonstrated in human medicine and will likely be an area of further study. An elevated troponin concentration should prompt the clinician to pursue further diagnostics including echocardiography, ECG or Holter monitoring, blood pressure, bloodwork, thyroid evaluation and sometimes infectious disease testing. 

 

About the Author

Darcy Adin, DVM, DACVIM

Dr. Darcy Adin is a Clinical Professor of Cardiology at the University of Florida, College of Veterinary Medicine.  She received her DVM from Cornell University in 1996.  She completed a rotating internship at VCA South Shore Animal Hospital in 1997 and a cardiology residency at the University of California, Davis in 1999, with ACVIM board certification in Cardiology in 2000.  Dr. Adin has held positions in both academic and private specialty practice.   Her clinical research focuses on the investigation of diuretic treatments and neurohormonal modulation of congestive heart failure.   

Images courtesy of Shutterstock

Become a member to receive articles in our quarterly publication!