Home 5 Clinical Diagnostic Insider 5 Evidence Emerging for More Use Cases for High-Sensitivity Troponin

Evidence Emerging for More Use Cases for High-Sensitivity Troponin

by | Jul 14, 2016 | Clinical Diagnostic Insider, Diagnostic Testing and Emerging Technologies, Testing Trends-dtet

In recent years there has been mounting interest in the clinical use of circulating biomarkers for prediction of risk and diagnosis of cardiovascular diseases. High-sensitivity cardiac troponin (hs-cTn) is one of these biomarkers. To date, the U.S. Food and Drug Administration (FDA) has not approved an hs-cTn assay for use in the United States, but experts predict these tests (currently used in Europe) could be approved in the United States within the next year. Two new studies published in JAMA Cardiology show how new, high-sensitive assays can speed the time to rule in or rule out diagnosis of an acute myocardial infarction (AMI) in patients presenting with chest pain and how the utility of this marker can be extended to evaluate risk of coronary heart disease (CHD) or heart failure (HF). For Diagnosis of Myocardial Infarction Patients with a possible AMI can be triaged within one hour after admission with no additional risk compared to the standard three-hour approach used in Europe, according to a study published online June 1 in JAMA Cardiology. The authors say that using a “low and sensitive” cutoff for hs-cTnI enables an accelerated diagnostic protocol resulting in either a safe discharge or more rapid treatment […]

In recent years there has been mounting interest in the clinical use of circulating biomarkers for prediction of risk and diagnosis of cardiovascular diseases. High-sensitivity cardiac troponin (hs-cTn) is one of these biomarkers. To date, the U.S. Food and Drug Administration (FDA) has not approved an hs-cTn assay for use in the United States, but experts predict these tests (currently used in Europe) could be approved in the United States within the next year.

Two new studies published in JAMA Cardiology show how new, high-sensitive assays can speed the time to rule in or rule out diagnosis of an acute myocardial infarction (AMI) in patients presenting with chest pain and how the utility of this marker can be extended to evaluate risk of coronary heart disease (CHD) or heart failure (HF).

For Diagnosis of Myocardial Infarction
Patients with a possible AMI can be triaged within one hour after admission with no additional risk compared to the standard three-hour approach used in Europe, according to a study published online June 1 in JAMA Cardiology. The authors say that using a “low and sensitive” cutoff for hs-cTnI enables an accelerated diagnostic protocol resulting in either a safe discharge or more rapid treatment initiation.

“Use of hsTn for rapid triage of patients presenting to the emergency department with chest pain is an application likely to be embraced by practitioners,” writes David Morrow, M.D., from Brigham and Women’s Hospital (Boston) in an accompanying editorial. “Despite this low pretest probability, physicians are obligated to exclude myocardial ischemia with a high degree of probability and engage in time-consuming and costly testing strategies to do so. To manage costs and the adverse effects of overcrowding in the emergency department, it is a high priority to rapidly and safely identify patients with a sufficiently low probability for acute coronary syndrome (less than 0.5 to 1.0 percent) so that they can be discharged efficiently and avoid unnecessary testing.”

The German-based researchers tested a one-hour algorithm to diagnose AMI using an hs-cTnI assay (ARCHITECT i2000SR; Abbott Diagnostics). The Biomarkers in Acute Cardiac Care study prospectively applied the assay for the diagnosis of AMI in 1,040 patients (median age, 65 years; 64.7 percent male) presenting to the emergency department at the University Medical Center Hamburg-Eppendorf with acute chest pain from July 19, 2013 to Dec. 31, 2014. A one-hour diagnostic algorithm was compared to the standard three-hour algorithm (currently included in the European Society of Cardiology guidelines) for diagnostic accuracy of the lower cutoff versus the recommended 99th percentile. Follow-up mortality was also evaluated (median follow-up time, 313 days). The one-hour diagnostic algorithm was validated in two additional independent cohorts totaling 4,009 patients.

The researchers found that the best performing cutoff value for the hs-cTnI assay was 6 ng/L. This cutoff was lower than the routinely used 99th percentile. With the application of the lower troponin I cutoff value of 6 ng/L, the rule-out algorithm showed a high negative predictive value of 99.8 percent (95% CI, 98.6%-100.0%) after 1 hour for non–ST-segment elevation MI type 1. The one-hour approach was comparable to a three-hour approach. Similarly, a rule-in algorithm based on troponin I levels provided a high positive predictive value with 82.8 percent. The lower cutoff also resulted in lower follow-up mortality (1.0 percent) versus the use of the 99th percentile (3.7 percent) for this assay.

Long-Term Changes in hs-cTnT Predict Poor Outcomes
Increases in hs-cTnT levels over a six-year timeframe are tied to incident CHD, death, and, HF, according to a study published online June 8 in JAMA Cardiology. Serial measurement of hs-cTnT adds clinically relevant information to baseline testing and may be useful in targeting prevention strategies to high-risk individuals, especially among persons with stage A or B HF, the authors say.

Previous studies established that single measurements of hs-cTnT are independently tied to adverse cardiovascular outcomes in those with disease, but in the present study the researchers assessed changes in hs-cTnT in asymptomatic, middle-aged adults participating in the multi-site Atherosclerosis Risk in Communities Study. Hs-cTnT levels were measured twice (six years apart) in 8,838 participants (mean age, 56 years; 59.0 percent female; 21.4 percent black), who were initially free of CHD and HF between Jan. 1, 1990 to Dec. 31, 2011.

The researchers found that incident, detectable hs-cTnT (baseline, less than 0.005 ng/mL; follow-up, 0.005 ng/mL or greater) was independently associated with subsequent CHD, HF, and death, compared to an hs-cTnT level less than 0.005 ng/mL at both visits. Among individuals with the most marked hs-cTnT increases (baseline, less than 0.005 ng/mL; follow-up, 0.014 ng/mL or greater) hazard ratios were as high as 4 for CHD and death and 8 for HF. On the other hand, risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50 percent from baseline.

“Currently, it seems irrefutable that biomarkers can predict risk in population-based cohorts,” writes James Januzzi Jr., M.D., from Massachusetts General Hospital (Boston) in an accompanying editorial. “What is needed now are efforts toward developing strategies to upwardly bend the survival curves of those with a biomarker signature of risk, leveraging the knowledge gained.”

Takeaway: As evidence mounts for the ability of hs-cTn to more rapidly diagnose AMI and better predict risk of cardiovascular disease and death, experts expect hs-cTn assays to soon be approved in the United States.

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