Cardiac Troponin Concentrations Research Articles

Colchicine for the Prevention of Myocardial Injury Following Elective PCI: A Randomized Clinical Trial

Purpose: Considering the potential benefits of colchicine in coronary artery diseases, we aimed to carry out the present study to assess the impact of colchicine in the prevention of myocardial injury following elective percutaneous coronary intervention (PCI). Methods: A randomized, single-blinded, clinical trial was carried out on 102 patients undergoing elective PCI. All patients received the standard treatment prior to performing PCI. Moreover, the intervention group received 1, 0.5, 0.5 mg colchicine 12 to 18 hours before, 30-60 min before, and 12 hours after PCI, respectively. Serum concentrations of cardiac troponin I (cTnI) were measured before, 8, and 24 hours after the procedure to assess myocardial damage during PCI. Results: There were no significant differences in cTnI levels at baseline (P = 0.839), 8 (P = 0.729), and 24 hours (P = 0.398) after PCI between the intervention and the control groups. Likewise, no significant differences were seen regarding the mean differences of cTnI at baseline and 8 hours (P =0.190), at baseline and 24 hours (P = 0.780), and 8 and 24 hours after PCI (P = 0.680) in both groups. Conclusion: The study did not support the potential benefit of colchicine in the prevention of myocardial injury following elective PCI. Conducting well-designed randomized clinical trials with adequate sample size is recommended.

Implementation of an early rule-out pathway for myocardial infarction using a high-sensitivity cardiac troponin T assay

ObjectivesPatients with suspected acute coronary syndrome and high-sensitivity cardiac troponin (hs-cTn) concentrations below the limit of detection at presentation are low risk. We aim to determine whether implementing this approach...

Elevation of Highly Sensitive Cardiac Troponin T Among End-Stage Renal Disease Patients Without Acute Coronary Syndrome.

BackgroundIn end-stage renal disease (ESRD), troponin T concentrations can be elevated even without cardiac ischaemia, which hampers the diagnosis of acute myocardial infarction (AMI). The objectives of our study were to determine the proportion of dialysisdependent ESRD patients without acute coronary syndrome (ACS) but with highly sensitive cardiac troponin T (hs-cTnT) levels above the 99th percentile upper reference limit and to evaluate the range of hs-cTnT among this population.MethodsA cross-sectional study was conducted at the haemodialysis (HD) unit of a tertiary hospital in Malaysia from January 2018 to February 2019. Dialysis-dependent ESRD patients were included and those with a recent history of ACS (within 30 days) were excluded. Pre-dialysed serum hs-cTnT levels were measured using Cobas e411. The upper limit of the 99th percentile value for troponin T was 14 ng/L.ResultsA total of 150 patients were recruited as study participants. The majority were female (62%) and of Malay ethnicity (94%), and the mean (SD) age was 45.19 (16.36) years old. The hs-cTnT range (min, max) was 11.39–738.30 ng/L and the median (interquartile range [IQR]) of hs-cTnT was 59.20 (83.41) ng/L. Elevated hs-cTnT levels were observed in 149/150 (99%) of the study participants (54/55 [98.2%] of the patients were on HD, and 95/95 [100.0%] of the patients were on continuous ambulatory peritoneal dialysis).ConclusionThis study supports prior research showing that even without ACS, most ESRD patients have elevated concentrations of cardiac troponin. Furthermore, our study illustrates the need to revisit the use of absolute troponin values when making a diagnosis of ACS in ESRD patients.

Lifetime obesity trends are associated with subclinical myocardial injury: The Trøndelag health study.

Obesity is associated with subclinical myocardial injury as quantified by concentrations of cardiac troponin T, but whether lifetime excess weight history is associated with increased concentrations of cardiac troponin I (cTnI) and how indices of abdominal adiposity and glycemic dysregulation affect these associations remain unclear. We analyzed cTnI with a high-sensitivity assay in 9739 participants in the Trøndelag Health (HUNT) Study at study visit 4 (2017-2019). BMI was assessed at study Visit 1 (1984-1986), 2 (1995-1997), 3 (2006-2008), and 4. Median age at visit 4 was 68.7 years and 59% were women. Concentrations of cTnI were detectable in 84.1% of study participants, with a median of 2.5 (1.5-4.5 ng/L). We identified three clusters of BMI trajectories from visit 1 to 4, (1) stable normal weight, (2) stable overweight, and (3) stable obesity. Participants in clusters 2 and 3 were at increased risk of elevated concentrations of cTnI at visit 4 (odds ratio 1.27, 95% CI 1.09-1.47, and odds ratio 1.70, 95% CI 1.33-2.17, p for trend <0.001). Participants in cluster 3 had 22.0 (95% CI 14.1-29.9) higher concentrations of cTnI compared to participants in cluster 1 (p for trend <0.001). Dysregulated glucose metabolism and abdominal obesity did not influence our results. Individuals with stable overweight or obesity are at increased risk of subclinical myocardial injury, independently of glycemic dysregulation and abdominal adiposity. Our data support a direct detrimental effect of long-standing obesity on cardiovascular health.

Temporal changes of biomarkers in myocardial infarction patients with non-obstructive compared to obstructive coronary arteries

Abstract Background About 5–10% of all myocardial infarction (MI) patients have non-obstructive coronary arteries (MINOCA). The pathobiology of MINOCA is largely unknown compared to myocardial infarction with obstructive coronaries (MI-CAD). Purpose To investigate whether baseline concentrations and temporal changes of circulating biomarkers may offer insights into the activation of pathophysiological pathways in MINOCA compared to MI-CAD. Methods From the PLATelet inhibition and patient Outcomes (PLATO) trial, we retrospectively identified 114 patients with MINOCA (adjudicated MI, coronary stenoses &amp;lt;50% and excluding patients with previous coronary revascularization) and 2750 patients with MI-CAD (adjucated MI and stenoses ≥50%) with available biomarker data. Concentrations of high sensitivity cardiac troponin T (hs-cTnT), C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were centrally measured by immunoassays in plasma samples obtained at randomization/baseline (median 15 hours from index event) and after one month. Differences in biomarker concentrations and their changes were evaluated by Wilcoxon-Mann-Whitney tests and data at one month were also analysed with adjusted linear regression models. Results In MINOCA patients, median concentrations decreased during one month from 238 to 9 ng/L for hs-cTnT, from 3.5 to 1.6 mg/L for CRP and from 507 to 228 pmol/L for NT-proBNP (Figure 1 and 2). In MI-CAD patients, median concentrations decreased from 198 to 13 ng/L for hs-cTnT, from 3.2 to 2.3 mg/L for CRP and increased from 372 to 566 pmol/L for NT-proBNP. Compared to MI-CAD, the baseline concentrations were higher in MINOCA for NT-proBNP (p=0.011), but similar for hs-cTnT (p=0.555) and CRP (p=0.834). However, patients with MINOCA had statistically larger reductions of concentrations from baseline to one month for hs-cTnT (p=0.002), CRP (p=0.005) and NT-proBNP (p&amp;lt;0.001) as compared to patients with MI-CAD. At one month, concentrations were lower in MINOCA than MI-CAD patients for all three biomarkers, which remained significant after adjustment for the baseline biomarker concentration, clinical characteristics and medications (p&amp;lt;0.001). Conclusions In MINOCA compared to MI-CAD patients, higher concentrations of NT-proBNP and similar concentrations of hs-cTnT and CRP at baseline indicate a higher degree of acute myocardial dysfunction but similar degree of acute myocardial injury and inflammation. Furthermore, concentrations of these biomarkers were lower at one month in MINOCA, suggesting other or less remaining underlying disease processes after MI in MINOCA than MI-CAD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The present study was supported by Swedish Foundation for Strategic Research/Swedish Association of Local Authorities and Regions. The PLATO study and the biomarker analyses were sponsored by AstraZeneca.

Troponin to risk stratify patients with suspected acute coronary syndrome for computed tomography coronary angiography

Abstract Background Patients with suspected acute coronary syndrome in whom myocardial infarction has been ruled-out are at risk of future adverse cardiac events. However, the optimal approach to risk stratify and investigate these patients is uncertain. Methods We performed a prospective cohort study of 250 patients presenting to the Emergency Department with suspected acute coronary syndrome and troponin concentrations below the sex-specific 99th centile (16 ng/L for women and 34 ng/L for men). Patients were recruited in a 2:1 fashion stratified by peak high-sensitivity cardiac troponin I concentration above and below the early rule-out threshold of 5 ng/L (167 patients with intermediate troponin concentrations between 5 ng/L and the sex-specific 99th centile threshold and 83 patients with troponin concentrations &amp;lt;5 ng/L). All patients underwent computed tomography coronary angiography after they were discharged from hospital. Results Overall, 37.6% (94/250) of patients had normal coronary arteries whilst 36.0% (90/250) and 26.4% (66/250) had non-obstructive and obstructive coronary artery disease, respectively. Patients with intermediate troponin concentrations were more likely to have coronary artery disease than those with troponin concentrations &amp;lt;5 ng/L (71.9% [120/167] versus 43.4% [36/83]; odds ratio 3.33 [95% confidence interval 1.92–5.78]). This association persisted irrespective of whether patients had anginal symptoms. Conversely, there was no difference in the prevalence of coronary artery disease between those with and without anginal symptoms (63.2% [67/106] and versus 61.8% [89/144]; odds ratio 0.92 [0.48–1.76]). The majority of patients found to have coronary artery disease did not have a prior diagnosis and were not on optimal preventative medical therapy prior to undergoing computed tomography coronary angiography (50.8% [61/120] and 61.0% [22/36], versus 61.7% [74/120] and 69.4% [25/36] in patients with intermediate versus low troponin concentrations, respectively). Conclusions In patients with suspected acute coronary syndrome who have myocardial infarction ruled out, those with intermediate cardiac troponin concentrations are three-times more likely to have coronary artery disease than those with low troponin concentrations. Conversely anginal symptoms did not discriminate between those with and without coronary artery disease. Further studies are required to determine if targeting computed tomography coronary angiography to those with intermediate cardiac troponin concentrations can improve the use of preventative medical therapies and clinical outcomes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The British Heart Foundation Odds ratio of coronary artery diseaseCumulative proportion with CAD

Coronary artery disease and cardiovascular outcomes in patients with type 2 myocardial infarction

Abstract Purpose To evaluate the role of coronary disease in predicting adverse cardiovascular events in patients with type 2 myocardial infarction. Background Type 2 myocardial infarction occurs due to imbalance in myocardial oxygen supply or demand without atherothrombosis. There is currently no consensus on how patients with type 2 myocardial infarction should be investigated or treated. Although non-cardiovascular mortality is common in this population, the incidence of future cardiovascular events is similar to those with myocardial infarction due to plaque rupture. Observational data suggest patients with type 2 myocardial infarction and underlying coronary artery disease may be at higher risk of cardiovascular events, but to date, most findings have been observed in selected rather than consecutive patient cohorts. Methods We conducted a secondary analysis of a multi-centre randomised controlled trial of 48,282 consecutive patients attending hospital with suspected acute coronary syndrome. In 9,115 patients, high-sensitivity cardiac troponin concentrations were &amp;gt;99th centile, and the diagnosis was adjudicated in line with the Fourth Universal Definition. Patients with type 2 myocardial infarction were stratified by the presence of previous coronary artery disease and evaluated for a primary outcome of cardiovascular death or Type 1 or 4b myocardial infarction at one year. Competing risk cox regression models were used to evaluate predictors of the primary outcome selected a priori on the basis of clinical importance, with adjustment for the competing risk of non-cardiovascular death. Results The diagnosis of type 1 and type 2 myocardial infarction was made in 55% (4,981) and 12% (1,121) of patients, respectively. Compared to patients without a previous diagnosis of coronary artery disease, those with coronary disease were older (78 vs 71) and more likely to be female (54% vs 46%). The incidence of future cardiovascular death or myocardial infarction was highest in patients with type 2 myocardial infarction and previous coronary disease (20%, 91/454), compared to those with type 2 myocardial infarction without known coronary disease (10%, 69/667, P&amp;lt;0.001), and was similar to patients with type 1 myocardial infarction (17%, 863/4981, Figure 1). After adjusting for cardiovascular risk factors, the presence of known coronary disease remained an important predictor for future cardiovascular death or myocardial infarction (adjusted Hazard Ratio 1.45, 95% confidence interval 1.03 to 2.03; Figure 2). Conclusion Coronary artery disease is an independent predictor of cardiovascular outcomes in patients with type 2 myocardial infarction. Further research is required to evaluate whether systematic investigation for coronary artery disease and targeted secondary prevention could improve outcomes in patients with type 2 myocardial infarction. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Figure 1Figure 2

The association between serum high-sensitivity cardiac troponin T and acute myocardial infarction in patients with suspected chronic coronary syndrome is modified by body mass index

BackgroundHigher systemic concentrations of cardiac troponins and biomarkers of inflammation and endothelial dysfunction as well as obesity are associated with increased risk of cardiovascular disease (CVD) and may share pathophysiological pathways. We sought to explore the association between serum high sensitive cardiac troponin T (hs-cTnT) and future acute myocardial infarction (AMI) according to body mass index (BMI) among patients with suspected chronic coronary syndrome (CCS), as well as interactions with C-reactive protein (CRP) and asymmetric dimethylarginine (ADMA). MethodsA total of 3879 patients with baseline hs-cTnT ≤ 30 ng/L who underwent elective coronary angiography due to chronic coronary syndrome (CCS) were followed to subsequent AMI or end of 2009. Risk associations between hs-cTnT and incident AMI were explored with Cox regression according to BMI categories <25 kg/m 2, 25–30kg/m2 and >30kg/m2 and quartiles of serum CRP and plasma ADMA. ResultsMedian (25 th −75 th percentile) age was 62 (54–69) years and 2773 (77.5%) were men. During median 7.5 (25 th −75 th percentile) (6.9–9.2) years of follow-up, 460 (11.9%) patients experienced an AMI. The risk relationship between hs-cTnT and incident AMI was stronger among patients in the higher vs lower BMI categories, HR 1.087 (1.055–1.119), P for interaction 0.043. A similar interaction was not found in categories of CRP or ADMA. ConclusionThe risk relationship of hs-cTnT with incident AMI was stronger in patients with higher BMI. Our results motivate further studies into potential pathophysiological mechanisms connecting hs-cTnT with increased cardiovascular risk.

Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association.

Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.

Prognostic Value of Troponin I with Echocardiography Assessment in Septic Patients

Abstract Background Sepsis is heterogenous with regard to factors such as causal microorganism, patient predisposition, co-morbidity and response to therapy, a key element and unifying feature is the manifestation of cardiovascular dysfunction. Elevated concentrations of cardiac troponin I (cTnI) are frequently observed in patients with severe sepsis and septic shock even in the absence of an acute coronary syndrome (ACS). Objective To evaluate the prognostic value of (cTnI) with echocardiography assessment in septic patients. Patients and Methods This study was conducted at the intensive care units of Ain Shams university hospitals. 20 patients of both sexes with age ranging from 18 to 70 years diagnosed with sepsis admitted to Intensive care unit were included in prospective observational study. Results Baseline cTnI had a significant positive correlation with follow up troponine (p = 0.0016). Baseline EF had a significant negative correlation with follow up troponine (p = 0.036). Using ROC-curve analysis, troponin level at a cutoff point (&amp;gt;1.9) predicted patients with mortality, with good (87%) accuracy, sensitivity= 90% and specificity= 90% (p &amp;lt; 0.01). Conclusion Elevated concentrations of cardiac troponin I (cTnI) are frequently observed in patients with sepsis and septic shock even in the absence of an acute coronary syndrome.

Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan’an district

Objective To detect the concentration of high-sensitivity cardiac troponin T (hs-cTnT) in healthy children aged 0–14 years by electrochemiluminescence immunoassay (ECLIA), so as to explore the differences in different ages and genders. The aim of this study is to establish the reference interval for hs-cTnT in healthy children aged 0–14 years. Methods After screening, 3463 healthy children, including 1924 boys and 1539 girls, were selected from 4617 children aged 0–14 years. They were divided into nine groups: one day (umbilical cord blood; ‘UCB’), one day (venous blood; ‘VB’), 2–28 days, 29 days–<3 months, 3–<6 months, 6 months–<1 year old, 1–< 3 years old, 3–< 6 years old and 6–14 years old. A nonparametric test was used to detect the hs-cTnT concentration. The upper limit of the reference interval is the mean of the 99th percentile after bootstrap sampling. Results Hs-cTnT levels conformed to a non-Gaussian distribution. There was no significant difference in the concentration of hs-cTnT between boys and girls in the general data, but there were differences between boys and girls in the 3–<6 years old and 6–14 years old age groups. Except for UCB and 2–28 days, the concentration of hs-cTnT was significantly different in other age groups. The level of hs-cTnT in neonatal serum (2–28 days) was the highest. In other groups, it decreased gradually with age and dropped to the reference range of adults (0–14ng/L) at one-year old. The upper limit of reference interval of hs-cTnT concentration in each group was, respectively, 60.8, 78.8, 96.6, 58.6, 34.2, 16.2, 11.4, 8.0 (7.8 female), and 7.9 (7.3 female) ng/L. Conclusions Referring to WS/T 402-2012 establishment of reference intervals for clinical laboratory testing projects and CLSI (Clinical and Laboratory Standards Institute) C28-A3 documents and the joint expert consensus of ESC (European Society of Cardiology) and ACC (American College of Cardiology) in 2007, we established the reference interval of hs-cTnT concentration in children aged 0–14 years in Chongqing Nan’an district of China which can provide certain reference value for clinical diagnosis and treatment of myocarditis and myocardial (micro) injury in children.

ОЦЕНКА ВЛИЯНИЯ ОЖИРЕНИЯ НА ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ У СОБАК

Dogs’ obesity in is a common pathology and is associated with genetic factors, feeding, housing conditions, physical inactivity. Many pathogenesis aspects of obesity development of small domestic animals are poorly studied, in particular, the development of dysfunction of the cardiovascular system is an insufficiently explored issue. The aim of this study was to study clinical, electrocardiographic, echocardiographic and biochemical parameters of blood serum of obese dogs. The objects of the study were Dachshund dogs with obesity (n = 12) and clinically healthy animals (n = 16). All animals went through a complex clinical examination, electrocardiographic, echocardiographic and laboratory studies. Parametric and nonparametric methods of statistical analysis were used in the study. It was found that dogs’ obesity is characterized by a significant increase of the respiratory rate at rest and during sleep, pulse rate, systolic, diastolic and mean arterial blood pressure. It was shown that in case of dogs’ obesity, there is a slight increase of the end-diastolic size and thickness of the free wall of the left ventricle, a shortening of the PQ interval, and voltage decrease of P, R, T deflections on electrocardiograms. There were no violations of contractility and systolic function of the left ventricular myocardium of obese dogs. It was found that the activity of alkaline phosphatase, alanine and aspartic aminotransferases, the concentration of cholesterol, triglycerides, total protein, malondialdehyde and ceruloplasmin significantly increased in blood serum of obese dogs. Dogs’ obesity does not form dogs’ syndrome of cytolysis of cardiomyocytes, as evidenced by unchanged serum activity of lactate dehydrogenase, creatine phosphokinase and cardiac troponin concentration.

The Main Causes and Mechanisms of Increase in Cardiac Troponin Concentrations Other Than Acute Myocardial Infarction (Part 1): Physical Exertion, Inflammatory Heart Disease, Pulmonary Embolism, Renal Failure, Sepsis

The causes and mechanisms of increased cardiac troponin T and I (cTnT and cTnI) concentrations are numerous and are not limited to acute myocardial infarction (AMI) (ischemic necrosis of cardiac myocytes). Any type of reversible or irreversible cardiomyocyte injury can result in elevated serum cTnT and cTnI levels. Researchers and practitioners involved in the diagnosis and treatment of cardiovascular disease, including AMI, should know the key causes and mechanisms of elevated serum cTnT and cTnI levels. This will allow to reduce or completely avoid diagnostic errors and help to choose the most correct tactics for further patient management. The purpose of this article is to discuss the main causes and mechanisms of increase in cardiac troponins concentrations in frequently occurring physiological (physical exertion, psycho-emotional stress) and pathological conditions (inflammatory heart disease, pulmonary embolism, chronic renal failure and sepsis (systemic inflammatory response)) not related to myocardial infarction.

Abstract P234: Hypertensive Disorders Of Pregnancy And Increased Levels Of Cardiac Troponin I After Delivery

Background: Cardiovascular functions and hemodynamics dramatically change during pregnancy such as cardiac output, expanded blood volume, reduced systematic vascular resistance, and heart chamber enlargement. Hypertensive disorders of pregnancy (HDP) may affect the cardiac load during pregnancy; however, the data about plasma concentration of cardiac troponin in pregnant women with HDP is very limited. Methods: We prospectively collected data of 751 pregnant women between 2012 and 2013 in Japanese general hospital. We analyzed laboratory data and echocardiographic findings after delivery. The elevated cTnI was defined as &gt;0.015 ng/mL because the normal population have serum cTnI of less than 0.015 ng/mL in this assay. Results: The HDP were observed in 32 patients; the elevated cTnI was observed 40 patients. The age of patients with HDP (33.7 ±4.3 years) was not different from that of those without HDP (33.3 ± 5.0 years). The brain natriuretic peptides levels were not different between those with and without HDP. The proportion of elevated cTnI was higher in those with HDP (21.8%) than those without (3.6%, P&lt;0.0001). After adjusting for confounders, the risk of elevated cTnI in those with HDP relative to those without HDP remained significant (odds ratio 4.52, 95% confidence interval 1.45-14.5). There were no women with reduced left ventricular ejection fraction. Conclusions: HDP was associated with elevated cTni, suggesting myocardial microinjury might occur more frequently in those with HDP.

Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.

Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice. In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction. Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]). Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.

Induction Therapy for AML with 90 Mg/m² Daunorubicin Results in Higher Troponin T Serum Levels in Comparison to Treatment with 60 Mg/m² Daunorubicin

Introduction : Induction therapy for acute myeloid leukemia (AML) based on 7 days of cytarabine and 3 days of anthracycline has been standard treatment for decades. However, the optimal dose level of anthracycline is still in question. This issue is addressed by the ongoing randomized controlled DaunoDouble trial comparing 60 mg/m² versus 90 mg/m² in standard 7+3 induction for patients with newly diagnosed AML (NCT02140242). Since cardiotoxicity is considered the most dangerous side effect of anthracyclines, we compared serum levels of cardiac markers between the two study arms in the course of chemotherapy and afterwards.Methods: Serum concentrations of NT-proBNP and cardiac troponin T were measured prior to induction therapy (day 0), before (day 2) and during daunorubicin administration (days 3, 4, 5) and on day 15. The induction treatment consisted of a 7+3 induction with daunorubicin at a dose of either 60 or 90 mg/m² (Group 60 and 90). By the time of analysis, data on highly sensitive measured troponin T concentrations at day 15 was available for 116 patients.Results: With regard to NT-proBNP concentrations no significant difference between study arms was found, but NT-proBNP levels of Group 90 remained constantly higher during daunorubicin administration. Whereas there was no considerable development concerning troponin T during induction therapy, at day 15 the median troponin T concentration of all patients was 8 ng/l and as such significantly higher compared to 5 ng/l before daunorubicin administration (Wilcoxon test; Z = -3.763; p < 0.001; r = 0.38 (medium effect size)). The proportion of patients with troponin T concentrations higher than 14 ng/l, which is the 99%-percentile of the healthy population, was 9.78 percent [95% CI: 3.60 - 15.97%] before daunorubicin administration and 16.50 percent [95% CI: 9.21 - 23.80%] on day 15. Significant correlations occurred between troponin T concentrations on day 15 and pre-treatment values of troponin T (Spearman's ρ = 0.502; p < 0.001) and NT-proBNP (Spearman's ρ = 0.245; p = 0.02). Prior to daunorubicin application, the median troponin T concentration was 5 ng/l in Group 60 and 6 ng/l in Group 90, respectively. On day 15, Group 90 had significantly higher troponin levels (ctrop, Group 90, median = 10 ng/l) than Group 60 (ctrop, Group 60, median = 7ng/l; Mann-Whitney U test; U = 1332; p = 0.021; r = 0.21 (small effect size)). The proportion of patients with troponin T concentrations higher than 14 ng/l was 14.55 percent [95% CI: 4.93 - 24.16%] in Group 60 and 18.75 percent [95% CI: 7.30 - 30.20%] in Group 90.Conclusion: Prospective cardiac monitoring of a large number of patients with identical disease and treatment shows that the cardiac impairment of daunorubicin administration during AML induction therapy resulted in a significant shift to higher troponin T levels. Patients within Group 90 had significant higher troponin T concentrations on day 15 with an average increase of 3 ng/l compared to Group 60. With respect to the prognostic value of troponin T (cf. ARIC study, CHS study), a higher risk of future cardiac complications could be assumed for Group 90. Long-term follow-up is necessary to draw more precise conclusions on the clinical impact of the cardiac marker kinetics. [Display omitted] DisclosuresStoelzel:medac: Other: Travel support. Mayer:Novartis: Research Funding; Eisai: Research Funding. Hochhaus:Pfizer: Research Funding; Novartis: Research Funding; Incyte: Research Funding; BMS: Research Funding; ARIAD: Research Funding; MSD: Research Funding. Rollig:Janssen: Research Funding; Bayer: Research Funding.

Impact of high-sensitivity cardiac troponin T on survival and rehospitalization after transcatheter aortic valve replacement.

Constant elevations of the serum concentration of cardiac troponin T (TnT) indicate a myocardial injury that may affect the long-term outcome of transcatheter aortic valve replacement (TAVR). We sought to investigate the impact of pre-TAVR TnT on outcomes after TAVR during long-term follow-up. In a retrospective, observational study we compared long term outcomes after TAVR between tertiles of preinterventional high-sensitivity TnT. Systematic follow-up was performed annually for 5 years. The primary endpoint was a composite of all-cause death and any rehospitalization. Between 2010 and 2018, 2,129 patients with severe aortic valve stenosis underwent TAVR at our institution (mean age 82.6 years, 57.2% female, logistic EuroSCORE 20.5± 15.8). Boundaries for TnT tertiles were <21 ng/L and >42 ng/L. The median follow-up was 895 days. Three-year incidences for the primary endpoint were 70.9%, 76.6%, and 81.7% in the low, middle, and high tertile (log rank p< .001). Compared with the first tertile, the corresponding adjusted hazard ratios were 1.23 (95%-CI 1.08-1.40, p< .001) and 1.50 (95%-CI 1.32-1.70, p< .001) for the second and third tertile. We found consistent differences between TnT strata for all-cause death (3-year incidences 23.3%, 33.3%, and 47.1%; adjusted p< .001) and rehospitalization (3-year incidences 64.7%, 68.7% and 72.0%; adjusted p< .001), including significant differences in deaths (p< .001). The association between TnT and outcome was independent of coronary artery disease or low aortic valve gradient. TnT before TAVR is strongly associated with all-cause death and rehospitalization during 3-year follow-up.

Diagnosis, Investigation and Management of Patients with Acute and Chronic Myocardial Injury.

The application of high-sensitivity cardiac troponins in clinical practice has led to an increase in the recognition of elevated concentrations in patients without myocardial ischaemia. The Fourth Universal Definition of Myocardial Infarction encourages clinicians to classify such patients as having an acute or chronic myocardial injury based on the presence or absence of a rise or a fall in cardiac troponin concentrations. Both conditions may be caused by a variety of cardiac and non-cardiac conditions, and evidence suggests that clinical outcomes are worse than patients with myocardial infarction due to atherosclerotic plaque rupture, with as few as one-third of patients alive at 5 years. Major adverse cardiovascular events are comparable between populations, and up to three-fold higher than healthy individuals. Despite this, no evidence-based strategies exist to guide clinicians in the investigation of non-ischaemic myocardial injury. This review explores the aetiology of myocardial injury and proposes a simple framework to guide clinicians in early assessment to identify those who may benefit from further investigation and treatment for those with cardiovascular disease.

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): Extended Follow-Up of a 2×2 Factorial, Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Candesartan and Metoprolol.

Adjuvant breast cancer therapy containing anthracyclines with or without anti-human epidermal growth factor receptor-2 antibodies and radiotherapy is associated with cancer treatment-related cardiac dysfunction. In the PRADA trial (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy), concomitant treatment with the angiotensin receptor blocker candesartan attenuated the reduction in left ventricular ejection fraction (LVEF) in women receiving treatment for breast cancer, whereas the β-blocker metoprolol attenuated the increase in cardiac troponins. This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial injury. In this 2×2 factorial, randomized, placebo-controlled, double-blind, single-center trial, patients with early breast cancer were assigned to concomitant treatment with candesartan cilexetil, metoprolol succinate, or matching placebos. Target doses were 32 and 100 mg, respectively. Study drugs were discontinued after adjuvant therapy. All 120 validly randomized patients were included in the intention-to-treat analysis. The primary outcome measure was change in LVEF assessed by cardiovascular magnetic resonance imaging from baseline to extended follow-up. Secondary outcome measures included changes in left ventricular volumes, echocardiographic peak global longitudinal strain, and circulating cardiac troponin concentrations. A small decline in LVEF but no significant between-group differences were observed from baseline to extended follow-up, at a median of 23 months (interquartile range, 21 to 28 months) after randomization (candesartan, 1.7% [95% CI, 0.5 to 2.8]; no candesartan, 1.8% [95% CI, 0.6 to 3.0]; metoprolol, 1.6% [95% CI, 0.4 to 2.7]; no metoprolol, 1.9% [95% CI, 0.7 to 3.0]). Candesartan treatment during adjuvant therapy was associated with a significant reduction in left ventricular end-diastolic volume compared with the noncandesartan group (P=0.021) and attenuated decline in global longitudinal strain (P=0.046) at 2 years. No between-group differences in change in cardiac troponin I and T concentrations were observed. Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decline in LVEF during extended follow-up. Candesartan during adjuvant therapy did not prevent reduction in LVEF at 2 years, but was associated with modest reduction in left ventricular end-diastolic volume and preserved global longitudinal strain. These results suggest that a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01434134.

The effects of Allopurinol on levels of cardiac troponin Following Non-ST Elevation Myocardial Infarction: A Pilot Randomized Clinical Trial

Purpose: Given the potential anti-ischemic effects of allopurinol, we aimed to assess whether allopurinol administration may reduce myocardial injury following non-ST elevation myocardial infarction (NSTEMI). Methods: A randomized clinical trial (RCT) was conducted on 100 individuals with NSTEMI. The intervention group (n=50) received 600 mg oral allopurinol at the time of diagnosis of NSTEMI, followed by 300 mg every day for two next days and the standard treatment of NSTEMI, while the control group (n=50) received only the standard treatment. Serum concentrations of cardiac troponin I (cTnI) were measured at baseline, and 8, 16, 24, and 32 hours after the treatment. Results: The baseline demographic and clinical data of the patients were not statistically different between the intervention and control groups (all P &gt; 0.05). The comparing estimated marginal mean ± standard error for cardiac troponin I (cTnI) levels revealed no significant difference between the study groups (2.93 ± .27, 2.25 ± .27; P=0.082). The linear mixed model results showed that the interaction of time and group was not statistically different (P=0.751). Moreover, there was a decreasing trend over time for cTnI in both groups (P=0.039). Conclusion: The present pilot RCT did not support the potential cardio-protective benefits of allopurinol administration on decreasing myocardial injury following NSTEMI.