Cardiac Troponin I Elevation in Hospitalized Patients Without Acute Coronary Syndromes

doi:10.1016/j.amjcard.2008.01.011

The American Journal of Cardiology

Volume 101, Issue 10, 15 May 2008, Pages 1384-1388

https://doi.org/10.1016/j.amjcard.2008.01.011 Get rights and content

Increase of cardiac troponins occurs in a variety of clinical situations in the absence of an acute coronary syndrome (ACS). Few data exist regarding the incidence, clinical characteristics, and predictive value of various cardiac diagnostic tests and outcome of patients with a non-ACS–related troponin increase. We studied 883 consecutive hospitalized patients with increased cardiac troponin I levels. The discharge diagnosis was reclassified and troponin increase attributed to ACS or another process. Clinical data and results of cardiac diagnostic tests were collected. Patients were followed for a median of 30 months. Three hundred eleven patients were classified as having a non-ACS–related troponin increase (35.2%). An alternative explanation for troponin increase was found in 99% of these patients. Troponin level had poor accuracy in discriminating patients with and without ACS (area under the receiver operating characteristics curve 0.63). Coronary angiography was frequently unhelpful in excluding a non-ACS–related troponin increase because 77% of patients in the non-ACS group had significant flow-limiting coronary artery disease. Patients with non-ACS–related troponin increase had significantly higher in-hospital (hazard ratio 2.8, 95% confidence interval 2.0 to 3.8) and long-term (hazard ratio 2.0, 95% confidence interval 1.6 to 2.5) mortalities compared with patients with ACS. In conclusion, cardiac troponin level is frequently increased in hospitalized patients in the absence of an ACS and portends poor short- and long-term outcomes. Most of these patients have an alternative explanation for cardiac troponin increase. Cardiac diagnostic procedures are frequently unhelpful in excluding a non-ACS–related troponin increase.

Section snippets

Methods

All adult patients hospitalized at Rambam Medical Center from January to December 2003 with increased cardiac troponin I level were considered for the study. Exclusion criteria were age <18 years, missing medical data, or when duration from beginning of symptoms to blood sampling for troponin analysis was not known.

Rambam Medical center is a 1,000-bed university hospital, serving about 300,000 citizens of the greater Haifa area and functioning as a referral center for northern Israel (1,300,000

Results

During the 11-month study period there were 116,536 visits to the emergency room and 67,022 admissions. Cardiac troponin I was measured in 7,473 patients and was increased in 901 (12%). Eighteen patients (2%) were excluded because their medical files were not available or because the delay from appearance of symptoms to troponin analysis was not known, leaving 883 patients who constituted the study group.

Of the 883 patients, 572 (65%) were diagnosed by us as having an ACS. Four hundred

Discussion

In the present study, 35% of patients with a troponin increase were considered to be unrelated to an ACS. Most patients with a clinical presentation inconsistent with ACS had an alternative diagnosis explaining the finding of increased troponin. The magnitude of troponin increase was not useful in diagnosing ACS, and cardiac diagnostic procedures including echocardiography and coronary angiography were frequently abnormal in patients without ACS. Increased troponin unrelated to ACS defines a

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Cited by (46)

Resource utilization and outcome among patients with selective versus nonselective troponin testing
2018, American Heart Journal
Citation Excerpt :
Further, nearly 70% of non-ACS patients with troponin elevation received a non-cardiac discharge diagnosis, most commonly infection, neurologic disorder, respiratory failure, or gastrointestinal illness. Although troponin elevation is common among patients hospitalized with acute non-cardiac conditions, acute coronary artery obstruction requiring revascularization is quite uncommon.4,12-16,22-29 For example, in a recent study, 14% of 2123 patients with acute ischemic stroke had troponin elevation.29
In patients with suspected acute coronary syndrome (ACS), troponin testing is effective for diagnosis and prognosis. Troponin testing has now expanded to include patients without suspected ACS. This nonselective troponin testing has unknown consequences for resource utilization and outcome. Therefore, we examined selective versus nonselective troponin testing with respect to patient characteristics, resource utilization, and outcome.
This retrospective 1-year study included all patients with troponin testing at a U.S. emergency department. Testing was classified as selective (ACS) or nonselective (non-ACS) based on admission ICD-9 codes. Troponin upper reference limit (URL) was ≥99th percentile.
Among 47,053 patients, troponin was measured in 9109 (19%) of whom 5764 were hospitalized. Admission diagnosis was non-ACS in 4427 (77%) and ACS in 1337 (23%). Non-ACS patients were older, 71± 17 versus 65± 16 years, with longer hospital stay, 77 versus 32 h, and greater 1-year mortality 22% versus 6.7%; P < .001. In patients with troponin ≥URL, revascularization was performed in 64 (4.7%) of non-ACS versus 213 (48%) of ACS; P < .001. In patients with troponin <URL, 1-year mortality was 16% in non-ACS versus 3.5% in ACS; P < .001. In those with troponin ≥URL, 1-year mortality was 35% in non-ACS versus 13% in ACS; P < .001. Death was non-cardiac in >80% of the non-ACS population
Contemporary troponin testing is frequently nonselective. The non-ACS and ACS populations differ significantly regarding clinical characteristics, revascularization rates, and outcomes. Troponin elevation is a powerful predictor of 1-year mortality in non-ACS, this association reveals an opportunity for risk stratification and targeted therapy.
In patients with suspected acute coronary syndrome (ACS), troponin testing is effective for diagnosis and prognosis. However, troponin testing has now expanded to include patients without suspected ACS. This nonselective troponin testing has unknown consequences for hospital resource utilization and patient outcome.
Our findings demonstrate contemporary troponin testing is largely nonselective (77% of testing was performed in patients without acute coronary syndrome). In comparison to patients with acute coronary syndrome, those with non-acute coronary syndrome are older, with longer hospital stay, lower revascularization rates, and greater 1-year mortality. Troponin elevation identifies a high-risk population in both acute coronary syndrome and non-acute coronary syndrome populations, yet effective treatment for the latter is lacking.
Causes of Troponin Elevation and Associated Mortality in Young Patients
2018, American Journal of Medicine
Citation Excerpt :
Among patients who do not have a myocardial infarction, elevated troponin levels, regardless of etiology, have been shown to be associated with worse outcomes, both in the hospital and long term.23-33 Similar to a previous study in an older population, which found that mortality was higher in patients without acute coronary syndrome compared with those with acute coronary syndrome,9 increased troponins due to causes unrelated to myocardial infarction in our younger study population were associated with worse long-term outcomes compared with acute myocardial infarction. The high mortality rate associated with nonmyocardial infarction causes in even a young cohort highlights the importance of identifying appropriate management strategies aimed at treating the underlying causes as well as addressing any modifiable risk factors that could be contributing to the increased mortality observed in these patients.
While increased serum troponin levels are often due to myocardial infarction, increased levels may also be found in a variety of other clinical scenarios. Although these causes of troponin elevation have been characterized in several studies in older adults, they have not been well characterized in younger individuals.
We conducted a retrospective review of patients 50 years of age or younger who presented with elevated serum troponin levels to 2 large tertiary care centers between January 2000 and April 2016. Patients with prior known coronary artery disease were excluded. The cause of troponin elevation was adjudicated via review of electronic medical records. All-cause death was determined using the Social Security Administration's death master file.
Of the 6081 cases meeting inclusion criteria, 3574 (58.8%) patients had a myocardial infarction, while 2507 (41.2%) had another cause of troponin elevation. Over a median follow-up of 8.7 years, all-cause mortality was higher in patients with nonmyocardial infarction causes of troponin elevation compared with those with myocardial infarction (adjusted hazard ratio [HR] 1.30; 95% confidence interval [CI], 1.15-1.46; P < .001). Specifically, mortality was higher in those with central nervous system pathologies (adjusted HR 2.21; 95% CI, 1.85-2.63; P < .001), nonischemic cardiomyopathies (adjusted HR 1.66; 95% CI, 1.37-2.02; P < .001), and end-stage renal disease (adjusted HR 1.36; 95% CI, 1.07-1.73; P = .013). However, mortality was lower in patients with myocarditis compared with those with an acute myocardial infarction (adjusted HR 0.43; 95% CI:, 0.31-0.59; P < .001).
There is a broad differential for troponin elevation in young patients, which differs based on demographic features. Most nonmyocardial infarction causes of troponin elevation are associated with higher all-cause mortality compared with acute myocardial infarction.
Prognostic Impact of Myocardial Injury Related to Various Cardiac and Noncardiac Conditions
2016, American Journal of Medicine
Elevated cardiac troponins in clinical conditions other than myocardial infarction are well known. For such occurrences, the term “myocardial injury” has been proposed. The long-term outcome in patients with myocardial injury related to various cardiac and noncardiac clinical disorders is unknown.
During January 2010 to January 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. Patients with cardiac troponin I values >30 ng/L and no evidence of myocardial ischemia were diagnosed as having myocardial injury. Patients were classified into 5 categories of plausible related conditions: cardiac ischemic, cardiac nonischemic, noncardiac, multifactorial, or indeterminate. Follow-up was a minimum of 3 years, with all-cause mortality as the single end-point.
A total of 3762 patients were considered, of whom 1089 (29%) had myocardial injury. The most common associated conditions were noncardiac (n = 346) or multifactorial (n = 359). Cardiac ischemic (n = 183) and cardiac nonischemic (n = 134) conditions occurred less frequently. After a median of 3.2 years, 645 patients (59%) had died. A multivariate Cox regression analysis showed no difference in mortality between patients with cardiac ischemic and cardiac nonischemic conditions (hazard ratio [HR] 0.75; 95% confidence interval [CI], 0.50-1.13; P = .2). Patients with noncardiac or multifactorial disorders, however, had significantly higher mortality than those with associated cardiac ischemic conditions (HR 1.39; 95% CI, 1.06-1.80; P = .02, and HR 1.94; 95% CI, 1.50-2.51; P <.001), respectively.
In patients with myocardial injury, the most common associated conditions were noncardiac or multifactorial. Of notice, these patients had significantly higher long-term mortality when compared with those with associated cardiac conditions.
Clinical Characteristics and Outcomes of Patients with Myocardial Infarction, Myocardial Injury, and Nonelevated Troponins
2016, American Journal of Medicine
Citation Excerpt :
We found that an acute myocardial infarction could be ruled out in more than two thirds of patients with cardiac troponin I elevations. Prior studies have reported percentages of 35% to 89%,13-18 and the disparity is most likely explained by the use of different upper reference limits rather than the 99th percentile and a coefficient of variation <10% at upper reference limit,14,15,17 and the inclusion of highly selected18 and small populations.13-15,18 With the availability of more sensitive assays, we are able to detect very low cardiac troponin I concentrations19 with an increasing proportion of patients having myocardial necrosis.20
Cardiac troponins have emerged as the preferred biomarkers for detecting myocardial necrosis and diagnosing myocardial infarction. However, current cardiac troponin assays do not discriminate between ischemic and nonischemic causes of myocardial cell death. Thus, when an increased troponin value is encountered in the absence of obvious myocardial ischemia, a careful search for other clinical conditions is crucial.
In 2010 to 2011, we prospectively studied hospitalized patients who had cardiac troponin I measured on clinical indication. An acute myocardial infarction was diagnosed in cases of a cardiac troponin I increase or decrease pattern with at least 1 value >30 ng/L (99th percentile) together with myocardial ischemia. Myocardial injury was defined as cardiac troponin I values >30 ng/L, but without signs or symptoms indicating overt cardiac ischemia. Patients with peak values ≤30 ng/L were classified as nonelevated cardiac troponin I. Follow-up was at least 3 years with all-cause mortality as the sole clinical end point.
A total of 3762 patients were included. Of these, 488 (13%) had acute myocardial infarction, 1089 (29%) had myocardial injury, and 2185 (58%) had nonelevated cardiac troponin I values. Patients with myocardial injury frequently presented with dyspnea, were older, and had more comorbidity than patients in the 2 other groups. During a median follow-up of 3.2 years, 1342 patients died. Mortality differed significantly between groups: 39% in those with myocardial infarction, 59% in those with myocardial injury, and 23% in those with nonelevated cardiac troponin I (log-rank test; P < .0001). No significant difference in mortality between patients with type 2 myocardial infarction and patients with myocardial injury was observed (63% and 59%, respectively).
Patients with myocardial injury are older and have more comorbidity than those with acute myocardial infarction. Both groups exhibit a poorer prognosis than patients with nonelevated cardiac troponin I values. Of note, a very high long-term mortality is observed in patients with type 2 myocardial infarction and patients with myocardial injury.
Troponin Rise in Hospitalized Patients With Nonacute Coronary Syndrome: Retrospective Assessment of Outcomes and Predictors
2015, Canadian Journal of Cardiology
Cardiac troponin is elevated in several clinical settings apart from thrombotic acute coronary syndrome (ACS) and is associated with increased adverse events. It is not clear whether troponin elevation in type II myocardial infarction (MI) is associated with increased cardiovascular events. Our objectives were to identify the cause of mortality in type II MI and to attempt to establish the threshold range of cardiac troponin-I (cTnI) elevation as well as clinical factors associated with adverse outcomes in type II MI.
This retrospective cohort study included 245 patients presenting with a noncardiac primary diagnosis associated with cTnI elevation at a single centre from January 2003 to December 2011. Primary outcome was a composite of cardiovascular and noncardiovascular mortality. Secondary outcomes included subsequent stroke, ACS, and heart failure (HF).
At 1 year, ACS occurred in 13 patients (5.3%), stroke was seen in 10 (4.1%) patients, and HF occurred in 19 (7.8%) patients. Overall 1-year mortality included 102 events (41.6%), with 10 cardiovascular deaths (9.8%), 65 noncardiovascular deaths (63.7%), and 27 (26.5%) deaths from unknown causes. In multivariable analysis, factors independently associated with increased overall 1-year mortality included cTnI elevation ≥ 4.63 μg/L (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.55-7.34; P = 0.002), age ≥ 70 years (OR, 2.44; 95% CI, 1.40-4.29; P = 0.002), and estimated glomerular filtration rate < 30 mL/min/1.73m² (OR, 2.40; 95% CI 1.31-4.40; P = 0.005).
Unlike the published literature, our study includes a variety of both operative and nonoperative clinical settings associated with troponin elevation. We illustrate that although overall mortality is high after type II MI, the majority of mortality is caused by noncardiovascular events.
La troponine cardiaque est élevée dans plusieurs contextes cliniques, mis à part le syndrome coronarien aigu (ACS) thrombotique, et est associée à des évènements défavorables accrus. Il n’est pas évident d’évaluer si l’élévation de la troponine lors d’un infarctus du myocarde (IM) de type II est associée à une augmentation dans le taux d’événements cardiovasculaires. Nos objectifs étaient d'identifier la cause de la mortalité lors d'IM de type II et de tenter d'établir l’intervalle du seuil de l’élévation de la troponine cardiaque I (cTnI) ainsi que les facteurs cliniques associés à des résultats défavorables dans l'IM de type II.
Cette étude de cohorte rétrospective a inclus 245 patients se présentant avec un diagnostic primaire non cardiaque associé à une élévation de la cTnI dans un seul centre de janvier 2003 à décembre 2011. Le point d’aboutissement principal était une combinaison de mortalité cardiovasculaire et non cardiovasculaire. Les points d’aboutissement secondaires incluaient les accident vasculaire cérébral (AVC), le syndrome coronarien aigu (SCA), et l'insuffisance cardiaque (IC).
À un an, des SCA sont apparus chez 13 patients (5,3 %), des AVC ont été observés chez 10 (4,1 %) patients, et des IC ont eu lieu pour 19 (7,8 %) patients. La mortalité globale à 1 an comprend 102 événements (41,6 %), dont 10 décès cardiovasculaires (9,8 %), 65 décès non cardiovasculaires (63,7 %), et 27 (26,5 %) décès de cause inconnue. En analyse multivariée, les facteurs indépendamment associés à l’augmentation de la mortalité globale à 1 an incluent l’élévation de la cTnI ≥ 4,63 μg/l (ratio d'incidence approché [RIA], 3,37; intervalle de confiance [IC] à 95 %, 1,55-7,34; P = 0,002), un âge ≥ 70 ans (RIA, 2,44; IC à 95 %, 1,40-4,29; P = 0,002), et un débit de filtration glomérulaire estimé < 30 ml/min/1,73m² (RIA, 2,40; IC à 95 %, 1,31-4,40; P = 0,005).
Contrairement à la littérature publiée, notre étude comprend une variété de contextes cliniques à la fois opératoires et non opératoires associés à une élévation de la troponine. Nous illustrons que, bien que la mortalité globale soit élevée après un IM de type II, la majorité de la mortalité est causée par des événements non cardiovasculaires.
Epinephrine-induced myocardial infarction in severe anaphylaxis: Is β-blocker a bad actor or bystander?
2013, American Journal of Emergency Medicine

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Coronary artery diseaseCardiac Troponin I Elevation in Hospitalized Patients Without Acute Coronary Syndromes

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

J Diabetes Complications

Chest

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Int J Cardiol

Am J Cardiol

Elevation of troponin I in sepsis and septic shock

Intensive Care Med

Causes of elevated troponin I with a normal coronary angiogram

Intern Med J

Pitfalls and problems of relying on serum troponin

QJM

Impaired renal clearance explains elevated troponin T fragments in hemodialysis patients

Circulation

Relation between troponin T concentration and mortality in patients presenting with an acute stroke: observational study

BMJ

Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded

Ann Intern Med

Coronary artery disease
Cardiac Troponin I Elevation in Hospitalized Patients Without Acute Coronary Syndromes