hs-troponins | Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Chest pain patients are often evaluated for acute myocardial infarction through troponin testing, which may prompt downstream services (cascades) of uncertain value.

Objective

Determine the association of high-sensitivity cardiac troponin (hs-cTn) assay implementation with cascade events.

Methods

Using electronic health record and billing data, we examined patient-visits to five emergency departments, April 1, 2017 – April 1, 2019. Difference-in-differences analysis compared patient-visits for chest pain (n=7,564) to patient-visits for other symptoms (n=100,415) (irrespective of troponin testing) before and after hs-cTn assay implementation. Outcomes included presence of any cascade event potentially associated with an initial hs-cTn test (primary), individual cascade events, length of stay, and spending on cardiac services.

Results

Following hs-cTn implementation, patients with chest pain had a 2.8% (95%CI 0.72, 4.9) net increase in experiencing any cascade event. They were more likely to have multiple troponin tests (10.5%, 95%CI 9.0, 12.0) and electrocardiograms (7.1 per 100 patient-visits, 95%CI 1.8, 12.4). However, they received net fewer computed tomography scans (-1.5 per 100 patient-visits, 95%CI -1.8, -1.1), stress tests (-5.9 per 100 patient-visits, 95%CI -6.5, -5.3), and cardiac catheterizations (-0.65 per 100 patient-visits, 95%CI -1.01, -0.30) and were less likely to receive cardiac medications, undergo cardiology evaluation (-3.5%, 95%CI -4.5, 2.6), or be hospitalized (-5.8%, 95%CI -7.7, -3.8). Chest pain patients had lower net mean length of stay (-0.24 days, 95%CI -0.32, -0.16) but no net change in spending.

Conclusions

Hs-cTn assay implementation was associated with more net upfront tests yet fewer net stress tests, catheterizations, cardiology evaluations, and hospital admissions in chest pain patients relative to patients with other symptoms.

Keywords

SOURCE

https://www.jacc.org/doi/10.1016/j.jacc.2021.04.049

UPDATED on 3/18/2020

Interference in Troponin Assays: What’s Going On?

— Heterophile antibodies, biotin, and more with Robert Christenson, PhD

by Andrew Perry, MD March 13, 2020

https://www.medpagetoday.com/blogs/ap-cardiology/85409

UPDATED on 5/1/2019

High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study

, and

Christie M. Ballantyne

Originally publishedhttps://doi.org/10.1161/CIRCULATIONAHA.118.038772Circulation. ;0

Abstract

Background: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD.

Methods: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation.

Results: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64-2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01-4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86-3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28-5.37), global CVD (HR, 3.01; 95% CI, 2.50-3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56-2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated (r=0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hsTnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD.

Conclusions: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.

Footnotes

* Corresponding Author; email: cmb@bcm.edu

SOURCE

https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.118.038772?utm_campaign=sciencenews18-19&utm_source=weekly-sn&utm_medium=email&utm_content=phd05-01-19&

UPDATED on 8/14/2018

Siemens Launches High-sensitivity Troponin Test for Faster Diagnosis of Heart Attacks

The new troponin I assays can detect lower levels of troponin compared to conventional testing

July 25, 2018 — The U.S. Food and Drug Administration (FDA) cleared Siemens Healthineers high-sensitivity troponin I assays (TnIH) for the Atellica IM and ADVIA Centaur XP/XPT in vitro diagnostic analyzers from Siemens Healthineers to aid in the early diagnosis of myocardial infarctions.

The new tests can shorten the time doctors need to diagnose a life-threatening heart attacks. The time to first results is 10 minutes. When a patient experiencing chest pain enters the emergency department, a physician orders a blood test to determine whether troponin is present. As blood flow to the heart is blocked, the heart muscle begins to die in as few as 30 to 60 minutes and releases troponin into the bloodstream.

The company said its high-sensitivity performance of the two new Siemens TnIH assays offers the ability to detect lower levels of troponin at significantly improved precision at the 99th percentile, and detect smaller changes in a patient’s troponin level as repeat testing occurs. This design affords clinicians greater confidence in the results with precision that provides the ability to measure slight, yet critical, changes to begin treatment.[1,2]

Chest pain is the cause of more than 8 million visits annually nationwide to emergency departments, but only 5.5 percent of those visits lead to serious diagnoses such as heart attacks.[3] Armed with data to properly triage patients sooner or to exclude myocardial infarctions, the Siemens Healthineers TnIH assays can help support testing initiatives tied to improving patient experience.

“Our emergency department is overcrowded with patients. If we can do a more efficient job at triaging patients to receive the proper level of care and to discharge the patients who do not need to stay in the emergency department, this will have a tremendous economic advantage for our healthcare system,” said Alan Wu, M.D., chief of clinical chemistry and toxicology at Zuckerberg San Francisco General Hospital and Trauma Center.

Siemens is launching the product at the 70th AACC Annual Scientific Meeting and Clinical Lab Expo taking place July 31 to Aug. 2 in Chicago.

For more information: http://www.siemens-healthineers.com

Watch the related VIDEO: Use of High Sensitivity Troponin Testing in the Emergency Department — Interview with James Januzzi, M.D., Massachusetts General Hospital

SOURCE

https://www.dicardiology.com/product/siemens-launches-high-sensitivity-troponin-test-faster-diagnosis-heart-attacks?eid=333021707&bid=2192216

References:

1. Eggers K, Jernberg T, Ljung L, Lindahl B. High-Sensitivity Cardiac Troponin-Based Strategies for the Assessment of Chest Pain Patients—A Review of Validation and Clinical Implementation Studies. Clin Chem. 2018;64(7). DOI: 10.1373/clinchem.2018.287342

2. Collinson P. High-sensitivity troponin measurements: challenges and opportunities for the laboratory and the clinician. Annals of Clinical Biochemistry. 2016;53(2) 191–195. DOI: 10.1177/0004563215619946

3. Hsia RY, Hale Z, Tabas JA. A National Study of the Prevalence of Life-Threatening Diagnoses in Patients With Chest Pain. JAMA Intern Med. 2016;176(7):1029–1032. DOI:10.1001/jamainternmed.2016.2498

Troponin Rise Predicts CHD, HF, Mortality in Healthy People: ARIC Analysis

Veronica Hackethal, MD

Increases in levels of cardiac troponin T by high-sensitivity assay (hs-cTnT) over time are associated with later risk of death, coronary heart disease (CHD), and especially heart failure in apparently healthy middle-aged people, according to a report published June 8, 2016 in JAMA Cardiology^[1].

The novel findings, based on a cohort of >8000 participants from the Atherosclerosis Risk in Communities (ARIC) study followed up to 16 years, are the first to show “an association between temporal hs-cTnT change and incident CHD events” in asymptomatic middle-aged adults,” write the authors, led by Dr John W McEvoy (Johns Hopkins University School of Medicine, Baltimore, MD).

Individuals with the greatest troponin increases over time had the highest risk for poor cardiac outcomes. The strongest association was for risk of heart failure, which reached almost 800% for those with the sharpest hs-cTnT rises.

Intriguingly, those in whom troponin levels fell at least 50% had a reduced mortality risk and may have had a slightly decreased risk of later HF or CHD.

“Serial testing over time with high-sensitivity cardiac troponins provided additional prognostic information over and above the usual clinical risk factors, [natriuretic peptide] levels, and a single troponin measurement. Two measurements appear better than one when it comes to informing risk for future coronary heart disease, heart failure, and death,” McEvoy told heartwire from Medscape.

He cautioned, though, that the conclusion is based on observational data and would need to be confirmed in clinical trials. Moreover, high-sensitivity cardiac troponin assays are widely used in Europe but are not approved in the US.

An important next step after this study, according to an accompanying editorial from Dr James Januzzi (Massachusetts General Hospital, Boston, MA), would be to evaluate whether the combination of hs-troponin and natriuretic peptides improves predictive value in this population^[2].

“To the extent prevention is ultimately the holy grail for defeating the global pandemic of CHD, stroke, and HF, the main reason to do a biomarker study such as this would be to set the stage for a biomarker-guided strategy to improve the medical care for those patients at highest risk, as has been recently done with [natriuretic peptides],” he wrote.

The ARIC prospective cohort study entered and followed 8838 participants (mean age 56, 59% female, 21.4% black) in North Carolina, Mississippi, Minneapolis, and Maryland from January 1990 to December 2011. At baseline, participants had no clinical signs of CHD or heart failure.

Levels of hs-cTnT, obtained 6 years apart, were categorized as undetectable (<0.005 ng/mL), detectable (≥0.005 ng/mL to <0.014 ng/mL), and elevated (>0.014 ng/mL).

Troponin increases from <0.005 ng/mL to 0.005 ng/mL or higher independently predicted development of CHD (HR 1.41; 95% CI 1.16–1.63), HF (HR 1.96; 95% CI 1.62–2.37), and death (HR 1.50; 95% CI 1.31–1.72), compared with undetectable levels at both measurements.

Hazard ratios were adjusted for age, sex, race, body-mass index, C-reactive protein, smoking status, alcohol-intake history, systolic blood pressure, current antihypertensive therapy, diabetes, serum lipid and cholesterol levels, lipid-modifying therapy, estimated glomerular filtration rate, and left ventricular hypertrophy.

Subjects with >50% increase in hs-cTnT had a significantly increased risk of CHD (HR 1.28; 95% CI 1.09–1.52), HF (HR 1.60; 95% CI 1.35–1.91), and death (HR 1.39; 95% CI 1.22–1.59).

Risks for those end points fell somewhat for those with a >50% decrease in hs-cTnT (CHD: HR 0.47; 95% CI 0.22–1.03; HF: HR 0.49 95% CI 0.23–1.01; death: HR 0.57 95% CI 0.33–0.99).

Among participants with an adjudicated HF hospitalization, the group writes, associations of hs-cTnT changes with outcomes were of similar magnitude for those with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).

Few biomarkers have been linked to increased risk for HFpEF, and few effective therapies exist for it. That may be due to problems identifying and enrolling patients with HFpEF in clinical trials, Dr McEvoy pointed out.

“We think the increased troponin over time reflects progressive myocardial injury or progressive myocardial damage,” Dr McEvoy said. “This is a window into future risk, particularly with respect to heart failure but other outcomes as well. It may suggest high-sensitivity troponins as a marker of myocardial health and help guide interventions targeting the myocardium.”

Moreover, he said, “We think that high-sensitivity troponin may also be a useful biomarker along with [natriuretic peptides] for emerging trials of HFpEF therapy.”

But whether hs-troponin has the potential for use as a screening tool is a question for future studies, according to McEvoy.

In his editorial, Januzzi pointed out several implications of the study, including the possibility for lowering cardiac risk in those with measurable hs-troponin, and that HF may be the most obvious outcome to target. Also, optimizing treatment and using cardioprotective therapies may reduce risk linked to increases in hs-troponin. Finally, long-term, large clinical trials on this issue will require a multidisciplinary team effort from various sectors.

“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 from studies such as the report by McEvoy et al to improve public health,” he concluded.

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Diagnostic Value of Cardiac Biomarkers

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Diagnostic Value of Cardiac Biomarkers

Author and Curator: Larry H Bernstein, MD, FCAP

These presentations covered several views of the utilization of cardiac markers that have evolved for over 60 years. The first stage was the introduction of enzymatic assays and isoenzyme measurements to distinguish acute hepatitis and acute myocardial infarction, which included lactate dehydrogenase (LD isoenzymes 1, 2) at a time that late presentation of the patient in the emergency rooms were not uncommon, with the creatine kinase isoenzyme MB declining or disappeared from the circulation. The world health organization (WHO) standard definition then was the presence of two of three:

1. Typical or atypical precordial pressure in the chest, usually with radiation to the left arm

2. Electrocardiographic changes of Q-wave, not previously seen, definitive; ST- elevation of acute myocardial injury with repolarization;
T-wave inversion.

3. The release into the circulation of myocardial derived enzymes –
creatine kinase – MB (which was adapted to measure infarct size), LD-1,
both of which were replaced with troponins T and I, which are part of the actomyosin contractile apparatus.

The research on infarct size elicited a major research goal for early diagnosis and reduction of infarct size, first with fibrinolysis of a ruptured plaque, and this proceeded into the full development of a rapidly evolving interventional cardiology as well as cardiothoracic surgery, in both cases, aimed at removal of plaque or replacement of vessel. Surgery became more imperative for multivessel disease, even if only one vessel was severely affected.

So we have clinical history, physical examination, and emerging biomarkers playing a large role for more than half a century. However, the role of biomarkers broadened. Patients were treated with antiplatelet agents, and a hypercoagulable state coexisted with myocardial ischemic injury. This made the management of the patient reliant on long term followup for Warfarin with the international normalized ratio (INR) for a standardized prothrombin time (PT), and reversal of the PT required transfusion with thawed fresh frozen plasma (FFP). The partial thromboplastin test (PPT) was necessary in hospitalization to monitor the heparin effect.

Thus, we have identified the use of traditional cardiac biomarkers for:

1. Diagnosis
2. Therapeutic monitoring

The story is only the beginning. Many patients who were atypical in presentation, or had cardiovascular ischemia without plaque rupture were problematic. This led to a concerted effort to redesign the troponin assays for high sensitivity with the concern that the circulation should normally be free of a leaked structural marker of myocardial damage. But of course, there can be a slow leak or a decreased rate of removal of such protein from the circulation, and the best example of this would be the patient with significant renal insufficiency, as TnT is clear only through the kidney, and TNI is clear both by the kidney and by vascular endothelium. The introduction of the high sensitivity assay has been met with considerable confusion, and highlights the complexity of diagnosis in heart disease. Another test that is used for the diagnosis of heart failure is in the class of natriuretic peptides (BNP, pro NT-BNP, and ANP), the last of which has been under development.

While there is an exponential increase in the improvement of cardiac devices and discovery of pharmaceutical targets, the laboratory support for clinical management is not mature. There are miRNAs that may prove valuable, matrix metalloprotein(s), and potential endothelial and blood cell surface markers, they require

1. codevelopment with new medications
2. standardization across the IVD industry
3. proficiency testing applied to all laboratories that provide testing
4. the measurement on multitest automated analyzers with high capability in proteomic measurement (MS, time of flight, MS-MS)