Coronary artery disease (CAD)—as identified by coronary computed tomography angiography (CCTA)—was three times more likely in patients with intermediate concentrations of high-sensitivity cardiac troponin I (hs-cTnI) in whom myocardial infarction had been excluded, compared with those with low hs-cTnI, according to results from the PRECISE-CTCA (Troponin to Risk Stratify Patient with Acute Chest Pain for Computed Tomography Coronary Angiography) study. The findings were published in the Journal of the American College of Cardiology.
Researchers concluded that in these patients, CCTA may help identify those with occult CAD, target preventive treatments, and improve clinical outcomes.
“The majority of patients presenting to the Emergency Room with chest pain have myocardial infarction ruled out, but there have been few studies to help clinicians identify those who might benefit from further investigation or follow up,” senior study author Nicholas L. Mills, MD, British Heart Foundation Chair of Cardiology, BHF Centre for Cardiovascular Science, University of Edinburgh, U.K., told BreakingMED.
“We know that high-sensitivity cardiac troponin is a powerful predictor of events in patients without myocardial infarction with those who have intermediate troponin concentrations at 10-fold higher risk of future myocardial infarction or cardiac death than those with low values, but the mechanisms underpinning this observation are uncertain,” he added.
In this prospective, observational study, Mills and colleagues sought to assess the value or benefits of using hs-cTnI in selecting patients for further assessments after the exclusion of myocardial infarction. They included 250 patients age 30 years and older (mean age: 61.4 years; 31% women) who had presented to the emergency department of the Royal Infirmary of Edinburgh, U.K., with suspected acute coronary syndrome in whom acute MI had been ruled out. All patients had peak hs-cTn concentrations within the normal range.
In all, 62.4% had CAD, 53.2% were previously undiagnosed, and 63.5% were not currently receiving antiplatelet or statin medications before undergoing CCTA.
All patients underwent outpatient CCTA as soon as possible after initial hospital attendance. CCTA was performed with a 128-detector row scanner with iodine-based contrast media, in line with guidelines from the Society of Cardiovascular Computed Tomography. All patients were treated with sublingual glyceryl trinitrate, and in those with heart rates greater than 60 beats/min also received rate-limiting medication. CCTA was used to classify patients according to stenosis; researchers also quantified atherosclerotic plaque burden according to segment involvement and stenosis and CT-adapted Leaman scores.
Mills et al found that patients with intermediate hs-cTnI concentrations—defined as 5 ng/L and the sex-specific 99th percentile—were more likely to have CAD than those with concentrations that were less than 5 ng/L (71.9% vs 43.4%, respectively; OR: 3.33; 95% CI: 1.92-5.78). These patients also had more atherosclerotic plaque burden (median segment involvement score: 20 vs 0.0; segment stenosis score: 3.0 vs 0.0; and CT-Leaman score: 5.2 vs 0.0).
In addition, patients with obstructive and nonobstructive CAD had higher median troponin concentrations compared with those with normal coronary arteries (7.5 and 7.0 ng/L vs 4.5 ng/L, respectively; P=0.001 for both).
In patients with troponin concentrations within the normal reference range, increasing troponin concentrations were correlated with increasing numbers of patients identified with any CAD, from 32.3% in those with concentrations below the limit of detection (1.2 ng/L), to 62.2% in those with concentrations ≥16 ng/L.
“Across this range of troponin concentrations, the cumulative proportion with obstructive CAD increased from 3.2% (1 of 31 patients) to 26.5% (61 of 230 patients),” wrote Mills and colleagues.
They found no associations, however, between CAD and symptoms of angina (63.2% vs 61.8%; OR: 0.92; 95% CI: 0.48-1.76), and similar atherosclerotic plaque burden in those with and without symptoms of angina (median segment involvement score 2.0 vs 2.0, respectively; P=0.787; segment stenosis score 2.0 vs 2.0; P=0.692; and CT-Leaman score 3.2 vs 3.2, P=0.749).
The prevalence of CAD was higher in patients with intermediate troponin concentrations compared with those with low concentrations in those with and without symptoms of angina (72.4% vs 40.0%; OR: 39.3; 95% CI: 1.62-9.54 and 71.4% vs 45.3%; OR: 3.02; 95% CI: 1.49-6.12, respectively).
“I think many clinicians would be surprised by the high prevalence of non-obstructive and obstructive coronary artery disease in this patient population. However, our findings are consistent with those from the recently published SCAPIS cohort in Sweden, which demonstrated that prevalence of coronary artery disease in the general adult population without symptoms is as high as 42%,” noted Mills.
“Current guidelines are unclear how to further evaluate patients without myocardial infarction with intermediate high-sensitivity cardiac troponin concentrations or those who are triaged to the observe zone. Our findings suggest a high proportion have coronary artery disease and patients may benefit from an early outpatient CCTA. We are currently evaluating whether troponin guided CCTA reduces the risk of future myocardial infarction or cardiac death compared to standard care in a large multicenter randomized controlled trial funded by the British Heart Foundation (TARGET-CTCA, Clincialtrial.gov: NCT03952351),” concluded Mills.
In an accompanying editorial, Kavitha Chinnaiyan, MD, of Beaumont Health, Royal Oak, Michigan, and James L. Januzzi, Jr., MD, of Massachusetts General Hospital, Baim Institute for Clinical Research, Boston, commented on these results from Mills and colleagues.
“Although the association between CAD and intermediate hs-cTn levels is not entirely unexpected, these data add to the ACP triage framework in the era of rapid testing and understanding that an hs-cTn threshold for ruling out an acute ischemic episode may be the tip of the iceberg, while information gained from those with ’normal’ hs-cTn might better inform the massive iceberg under the waterline when it comes to the burden of CAD. Combining tests judiciously may allow us to be in the unique position of having our cake and eating it too, where safe triage of ACP with a sensitive biomarker is combined with preventive therapy for CAD detected by a sensitive imaging test,” they wrote.
“As every clinician knows, there is not one perfect test, and the art of medicine requires balancing the most effective combination of investigations. Instead of focusing entirely on the ’rule-out’ threshold of high-sensitivity troponin, perhaps the time has come to consider the actual troponin values in an individual patient to determine the need for additional testing with CTA.,” conclude Chinnaiyan and Januzzi.
Limitations of the study include its observational nature, the evaluation of CAD severity base on coronary artery stenosis rather than plaque phenotyping or CT fractional flow reserve, the low prevalence of CAD, and possible patient selection bias.
In patients in whom MI has been ruled out, those with intermediate troponin concentrations were 3x more likely to have CAD on CCTA than those with low troponin concentrations.
Conversely, symptoms of angina did not discriminate between patients with CAD and those without.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
Mills was supported by a Chair Award, Programme Grant, and Research Excellence Award from the British Heart Foundation.
Chinnaiyan is a member of the Executive Committee and Board of Directors of SCCT; and her institution has received a research grant from HeartFlow, Inc.
Januzzi is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Applied Therapeutics, Innolife, Novartis Pharmaceuticals, and Abbott Diagnostics; has received consulting income from Abbott, Janssen, Novartis, and Roche Diagnostics; and has participated in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, MyoKardia, and Takeda.
Cat ID: 914
Topic ID: 74,914,730,914,192,925,481,96