Elevated cardiac troponin (cTn) without a clear etiology is no benign condition for patients with chest pain, according to researchers who urged that the finding of myocardial injury should be followed by careful work-up in these patients.
One in three of those in the highest cTn tertile above the 99th percentile indicative of myocardial injury but who were discharged without diagnosis of a cardiac event later died, had an MI or stroke, or were admitted for heart failure over a median 4.9 years of follow-up in the SWEDEHEART registry.
This group significantly exceeded the normal troponin group in risk (HR 2.59, 95% CI 2.39-2.80), Kai Eggers, MD, PhD, of Uppsala University in Sweden, and colleagues reported in the January 8/15 issue of Journal of the American College of Cardiology.
Even the “healthiest” patients in that high cTn group — those without cardiovascular comorbidities, renal dysfunction, left ventricular dysfunction, or significant coronary stenosis — showed increased odds of major events (HR 3.57, 95% CI 2.30-5.54).
“Our data are in line with results from studies investigating cTn levels in other populations without acute cardiovascular disease,” the researchers wrote. “A common denominator of these studies is the mediation of the prognostic importance of cTn through its association with cardiac abnormalities. These might possibly still be subclinical at the time point of cTn measurement.”
In the SWEDEHEART registry (n=48,872), one in five people admitted acutely for a suspected ACS had cTn levels exceeding the 99th percentile.
Their risk of major adverse events (all-cause mortality, MI, heart failure readmission, or stroke) climbed in a stepwise fashion when further divided into tertiles by cTn compared with people below the 99th percentile, whose rate of events was 271.5 per 10,000 patient-years:
- Tertile 1 (lower cTn): 419.1 per 10,000 patient-years
- Tertile 2: 562.4 per 10,000 patient-years
- Tertile 3 (highest cTn): 1,046.1 per 10,000 patient-years
“Troponinemia” has been used to describe elevated cTn with no clear reason, but it is “trivializing and should be avoided,” the investigators argued.
The next steps after finding abnormal troponin could include a cTn retest (perhaps using a different assay), referral for echocardiography, and invasive or noninvasive coronary imaging, depending on the person’s pre-test probability of coronary artery disease, Eggers’ group said.
Liberal referral to imaging would be a good idea if not for the cost implications and risks for overtesting, or the fact that there is no evidence that revascularization benefits patients with myocardial injury who have no obvious coronary ischemia, cautioned James Januzzi, Jr., MD, and Cian McCarthy, MB BCh, both of Boston’s Massachusetts General Hospital.
In an accompanying editorial, they emphasized that myocardial injury — defined as nonischemic troponin elevation under the fourth universal definition of MI — is still real injury and “should be referred to as such.”
“When acute myocardial necrosis is detected in patients without other obvious signs or symptoms of MI, it often leads to cognitive dissonance and frustration with the test. With [high-sensitivity] cTn assays, this is inevitably going to increase in frequency,” Januzzi and McCarthy predicted.
The registry study had 99th percentile cutoffs for cTn-I and cTn-T as 30 ng/l and 10 ng/l, respectively. Investigators observed that the higher the cTn classification, the greater the prevalence of cardiovascular risk factors (except smoking).
Eggers and colleagues acknowledged that their dataset was missing some information and may have been subject to errors in data entry.
TOTAL-AMI was funded by the Swedish Foundation of Strategic Research.
Eggers reported a research grant from Abbott Laboratories.
Januzzi disclosed grant support from Roche Diagnostics, Abbott Diagnostics, Singulex, Prevencio, and Cleveland Heart Labs; consulting income from Roche Diagnostics, MyoKardia, Abbott, and Critical Diagnostics; and participation in clinical endpoint committees/data safety monitoring boards for Boehringer Ingelheim, Amgen, AbbVie, Janssen, Abbott, and Siemens Diagnostics.
McCarthy reported no conflicts of interest.