Concentrations Of High-sensitivity Cardiac Troponin Research Articles

High-sensitivity cardiac troponin I-guided combination angiotensin receptor blockade and beta blocker therapy to prevent anthracycline cardiotoxicity: the Cardiac CARE RCT

Background Anthracycline-induced cardiotoxicity has a variable incidence, and the development of left ventricular dysfunction is preceded by rises in plasma cardiac troponin concentrations. Beta-adrenergic receptor blocker and renin-angiotensin-system inhibitor therapies have been associated with modest cardioprotective effects in unselected patients receiving anthracycline chemotherapy. Methods In a multicentre prospective randomised open-label blinded end-point trial, patients with breast cancer and non-Hodgkin lymphoma receiving anthracycline chemotherapy underwent plasma high-sensitivity cardiac troponin concentration monitoring and cardiac magnetic resonance imaging before and 6 months after anthracycline treatment. Randomised controlled trial – patients at high risk of cardiotoxicity (plasma cardiac troponin I concentrations in the upper tertile during chemotherapy) were randomised to standard care plus cardioprotection (combination carvedilol and candesartan therapy) or standard care alone. The primary end point was 6-month change in left ventricular ejection fraction. Prognostic cohort study – in low-risk non-randomised patients with plasma cardiac troponin I concentrations in the lower two tertiles, we hypothesised the absence of a 6-month change in left ventricular ejection fraction (± 2%). Results Between October 2017 and June 2021, 175 patients (mean age 53 years; 87% female; 71% breast cancer) were recruited. Patients randomised to cardioprotection (n = 29) or standard care (n = 28) had mean left ventricular ejection fractions of 65.7 ± 6.6% and 64.9 ± 5.9%, respectively, at 6 months. Twenty patients (68.9%) were adherent to cardioprotection therapy at 6 months. Adverse events were more commonly reported in the cardioprotection group, with 71.4% of patients having at least one adverse event compared with 12.7% non-randomised and 10.3% standard care patients. After adjusting for age, pre-treatment left ventricular ejection fraction and planned anthracycline dose, the estimated mean percentage-point difference in 6-month left ventricular ejection fraction between the cardioprotection and standard care groups was –0.4% (95% confidence interval –3.59 to 2.85%; p = 0.82). In low-risk non-randomised patients, baseline and 6-month left ventricular ejection fractions were 69.3 ± 5.7% and 66.4 ± 6.3%, respectively (estimated mean difference 2.9%, 95% confidence interval 1.45 to 4.28%; p = 0.92, not equivalent). The main secondary objective of demonstrating zero percentage-point change with equivalence of ± 2% was not met. Conclusions Combination candesartan and carvedilol therapy had no demonstrable cardioprotective effect in patients receiving anthracycline-based chemotherapy with high-risk on-treatment plasma cardiac troponin I concentrations. Low-risk non-randomised patients had similar modest declines in left ventricular ejection fraction, suggesting that the clinical utility of routine cardiac troponin monitoring remains undefined. The modest short-term declines in left ventricular ejection fraction suggest that early cardioprotection therapy has a limited role in patients receiving anthracycline-based chemotherapy. Limitations Treatment effect might have been influenced by several patients stopping cardioprotection treatment within 2 months of randomisation. Across all groups, reduction in left ventricular ejection fraction was lower than expected and patients with high-risk cardiac troponin I concentrations did not exhibit a greater fall in left ventricular ejection fraction than low-risk patients. These factors, together with the trial being powered to detect a 5-percentage-point change in left ventricular ejection fraction, mean that a small treatment effect was not excluded. Future work Future work should aim to understand the transition from small changes in cardiac function, 6 months after completion of anthracycline chemotherapy, to the late development of heart failure in this population. Trial registration This trial is registered as ISRCTN24439460 and EudraCT 2017-000896-99. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 15/48/20) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 12. See the NIHR Funding and Awards website for further award information.

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1h and after 6-12months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1h algorithm and assessed biological variation at 6-12months using two established methods: reference change value (RCV) and minimal important difference (MID). Median baseline hs-cTnT concentrations were 34.4ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6months (IQR: 6-7). Median concentration change was 1.9ng/L (IQR: 0.7-3.2) and 0.8ng/L (IQR: 0-7.0) at 60min and 6-9months, respectively. Applying the criteria of the ESC 0/1h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT≥52ng/L. Biological variabilities at 6-12months per MID and RCV were 1.2ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Cardiovascular medications, high-sensitivity cardiac troponin T concentrations, and long-term outcome in non-ST segment elevation acute coronary syndrome.

Cardiac troponin plays an essential role in the management of non-ST segment elevation acute coronary syndrome (NSTE-ACS). However, it is not clear whether troponin concentrations provide guidance regarding the initiation of prognostically beneficial cardiovascular medications [i.e. betablockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and statins] in NSTE-ACS. Registry-based study investigating three NSTE-ACS cohorts (n = 43 075, 40 162, and 46 698) with elevated high-sensitivity cardiac troponin concentrations >14 ng/L. Cox proportional regression models with the addition of interaction terms were used to analyse the interrelations of high-sensitivity cardiac troponin T (hs-cTnT) concentrations, new initiated medications with the respective three drug classes, and long-term risk of all-cause mortality and major adverse events (MAE). Betablockers were associated with risk reductions of 8 and 5% regarding all-cause mortality and MAE, respectively. There was no evidence of an interaction with hs-cTnT concentrations. RAAS inhibitors were associated with 13 and 8% risk reductions, respectively, with a weak interaction between hs-cTnT and MAE (Pinteraction = 0.016). However, no increasing prognostic benefit was noted at hs-cTnT concentrations >100 ng/L. Statins were associated with 38 and 32% risk reductions, respectively, with prognostic benefit across the entire range of hs-cTnT concentrations, and with a weak interaction regarding MAE (Pinteraction = 0.011). Cardiovascular medications provide different prognostic benefit in patients with NSTE-ACS with elevated hs-cTnT, and there was some evidence of greater treatment effects regarding MAE along with higher hs-cTnT concentrations. However, hs-cTnT appears only to have limited value overall for customizing such treatments.

Temporal biomarker concentration patterns during the early course of acute coronary syndrome.

Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking. We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns. The study population consisted of 16,944 patients (median age 62 years; 71.3 % males) with 6,853 (40.3 %) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7 %) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex. Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.

Does a high baseline high sensitivity cardiac troponin T allow for the early diagnosis of acute myocardial infarction?

Abstract Background Guidelines suggest that the diagnosis of acute myocardial infarction (MI) is likely when high concentrations of high-sensitivity cardiac troponin (hs-cTn) are present in the initial sample. These concentration thresholds are much higher than the 99th percentile and are said to provide a high positive predictive value (PPV) for acute MI1. Purpose Evaluate the PPV of recommended baseline hs-cTnT thresholds (&amp;gt;52 and &amp;gt;100 ng/L) for the diagnosis of acute MI from our multi-center United States (US) experience. Methods Retrospective, multicenter (n=22), observational biomarker study involving consecutive, adult patients presenting to the emergency department (ED) in whom at least 1 hs-cTnT measurement was obtained within 12 hours of presentation (CV DataMart Biomarker cohort). The primary endpoint was also evaluated in an adjudicated cohort of consecutive patients presenting to the ED with at least 1 hs-cTnT &amp;gt;99th percentile (ACTION cohort). These cases were adjudicated based on the Fourth Universal Definition of MI by trained physicians. The primary efficacy endpoint was the PPV of acute MI (type 1 or 2), type 1 MI and type 2 MI during index hospitalization using baseline hs-cTnT thresholds of &amp;gt;52 ng/L and &amp;gt;100 ng/L. Results The CV DataMart Biomarker cohort consisted of 143,709 patients, amongst whom 3,003 (2.1%) were diagnosed with acute MI using ICD codes. In the CV DataMart Biomarker cohort, baseline hs-cTnT concentrations of &amp;gt;52 ng/L and &amp;gt;100 ng/L resulted in PPVs of 12% (95% CI: 11, 12) and 17% (95% CI: 17, 19) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations &amp;gt;52 ng/L, PPV for acute MI was 17% (95% CI: 15, 18), and in those with hs-cTnT concentrations &amp;gt;100 ng/L, PPV was 22% (95% CI: 19, 25). The adjudicated ACTION cohort consisted of 2,107 patients, amongst whom 155 (7.4%) were diagnosed with acute MI including 64 (41%) with type 1 MI and 91 (59%) with type 2 MI. In the ACTION cohort, baseline hs-cTnT concentrations of &amp;gt;52 ng/L and &amp;gt;100 ng/L resulted in PPVs of 46% (95% CI: 40, 53) and 62% (95% CI: 53, 70) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations &amp;gt;52 ng/L, PPV was 67% (95% CI: 57, 76) for acute MI, 52% (95% CI: 41, 62) for type 1 MI and 15% (95% CI: 8.4, 24) for type 2 MI. In those with chest pain and baseline hs-cTnT concentrations &amp;gt;100 ng/L, PPV was 77% (95% CI: 65, 87) for acute MI, 64% (95% CI: 51, 75) for type 1 MI and 14% (95% CI 6.4, 24) for type 2 MI (Figure). Conclusion Using previously recommended high-risk hs-cTnT thresholds of 52 and 100 ng/L in US patients provides reasonable performance to rule-in acute MI when used in patients with chest pain. When used more broadly across all-comers, the diagnostic performance is poor.

Association Between All-Cause Mortality and High-Sensitivity Cardiac Troponin Concentrations in Patients With Chest Pain.

We assessed the association between troponin levels and all-cause mortality in individuals with chest pain who presented to the Charleston Area Medical Center Emergency Department (CAMC). We identified adult patients with chest pain as defined in the International Classification of Diseases 10 (R07) family group from the CAMC data warehouse between June 6, 2020, and June 6, 2021. These cases required a visit to the emergency room. We created 3 different cohorts to assess the endpoints of all-cause mortality at 30days and 6months. Patients were divided into the following 3 categories: negative troponin level, defined as high sensitivity troponin I (HSTNI) assay ≤15pg/mL for women and ≤20pg/mL for men; weakly positive, 21-88pg/mL for men and 16-88pg/mL for women; and strongly positive, >88pg/mL for men and women. A propensity score matching analysis was also conducted using the negative group as a control; the weakly and strongly positive groups were compared to the control across differing cardiology covariates. This study introduces novel cutoffs for high-sensitivity troponin I (Beckman Coulter assay, Beckman Coulter, Inc., Chaska Campus, 1000 Lake Hazeltine Drive, Chaska, Minnesota 55318).

High-Sensitivity Troponin T and I Among Pregnant Women in the US—The National Health and Nutrition Examination Survey, 1999-2004

This cross-sectional study investigates the expected physiologic concentrations of high-sensitivity cardiac troponin in normal pregnancy.

D-18 | High-Sensitivity Cardiac Troponin Concentrations in Patients with Chest Discomfort

We sought to assess the association with different Troponin levels and mortality in patients with chest pain in the Charleston Area Medical Center Emergency Department. Our study used Beckman Coulter assay and introduce novel cut offs that helps develop chest pain algorithms.

Associations between cardiovascular risk factors, biomarkers, and left ventricular mechanical dispersion: insights from the ACE 1950 Study.

AimsMechanical dispersion measures left ventricular contraction heterogeneity and is associated with the risk of sudden cardiac death. However, the associations between mechanical dispersion and cardiovascular risk factors in early mid-life, and established biomarkers of sub-clinical myocardial injury and dysfunction are not known. We aimed to examine this in the general population.Methods and resultsDuring 2012–15, we included 2527 Norwegian individuals from the general population born in 1950, with measurements of mechanical dispersion by 2D speckle tracking echocardiography and concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) available. Mechanical dispersion was calculated as the standard deviation of the contraction duration of 17 strain segments. We assessed the associations between mechanical dispersion, concentrations of hs-cTnT and NT-proBNP, and cardiovascular risk factors collected at a national health screening survey two decades earlier. At echocardiography baseline, median age was 64 (interquartile range 63.5–64.5) years, 49.8% were women, 59.1% had hypertension, and 5.9% reported established coronary artery disease. Median mechanical dispersion was 38.0 (29.5–47.0) ms, median hs-cTnT concentration 6 (4–8) ng/L, and the median NT-proBNP concentration 54 (34–93) ng/L. Mechanical dispersion was associated with both hs-cTnT and NT-proBNP concentrations in multivariable models adjusted for clinical and echocardiographic variables. High body mass index, serum triglyceride concentrations, and low resting heart rate at Age 40 were independently associated with increased mechanical dispersion two decades later.ConclusionEstablished risk factors at Age 40 are associated with mechanical dispersion two decades later, and mechanical dispersion is cross-sectionally associated with biomarkers of subclinical myocardial injury and dysfunction.

Unstable Angina Pectoris With Myocardial Injury Versus Myocardial Infarction in the Era of High-Sensitivity Cardiac Troponin

It is unknown whether outcomes in patients with unstable angina pectoris (UAP) and myocardial injury are different from outcomes in patients with non-ST-segment myocardial infarction (NSTEMI) with low peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT). This study aimed to compare the prognosis in patients with UAP and evidence of myocardial injury, with prognosis in patients with NSTEMI and different peak hs-cTnT concentrations. All visits to 7 different emergency departments in Sweden from December 9, 2009 to December 31, 2016 were identified (n=5,225,075). We included all hospitalized patients with hs-cTnT >14ng/L and a diagnosis of UAP or NSTEMI, with ≥2hours-cTnT measurements. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for all-cause mortality and cardiovascular events, in patients with NSTEMI categorized according to peak hs-cTnT concentrations, compared with patients with UAP. Altogether, 11,944 patients were included, of whom 1,253 (10%) received a diagnosis of UAP. During a median follow-up of 3.0 years (interquartile [IQR] 1.6 to 4.7), 3,297 patients died. There was no difference comparing patients with NSTEMI with peak hs-cTnT of 15 to 49ng/L to patients with UAP, with regards to long-term cardiovascular mortality (HR 1.15; 95% CI, 0.85 to 1.56), but the risk of recurrent myocardial infarction was higher in patients with NSTEMI (HR, 1.61; 95% CI, 1.29 to 2.00), and the risk of heart failure hospitalization slightly lower (HR 0.80, 95% CI, 0.64 to 0.99). In conclusion, patients with UAP and myocardial injury have a similar risk of death after discharge, but a lower risk of recurrent myocardial infarction and a marginally higher risk of heart failure, compared with patients with NSTEMI with moderately elevated hs-cTnT levels.

Post-marathon Decline in Right Ventricular Radial Motion Component Among Amateur Sportsmen.

Moderate physical activity has a positive impact on health, although extreme forms of sport such as marathon running may trigger exercise-induced cardiac fatigue. The explicit distinction between the right ventricular (RV) physiological response to training and maladaptive remodeling has not yet been determined. In this study, we aimed to analyze the impact of running a marathon on RV mechanics in amateur athletes using three-dimensional (3D) echocardiography (ECHO) and the ReVISION method (RV separate wall motion quantification). A group of 34 men with a mean age of 40 ± 8 years who successfully finished a marathon underwent ECHO three times, i.e., 2 weeks before the marathon (stage I), at the marathon finish line (stage II), and 2 weeks after the marathon (stage III). The ECHO findings were then correlated with the concentrations of biomarkers related to myocardial injury and overload and also obtained at the three stages. On finishing the marathon, the amateur athletes were found to have a significant (p < 0.05) increase in end-diastolic (with a median of 51.4 vs. 57.0 ml/m2) and end-systolic (with a median of 24.9 vs. 31.5 ml/m2) RV volumes indexed to body surface area, reduced RV ejection fraction (RVEF) (with a median of 51.0% vs. 46.0%), and a decrease in RV radial shortening [i.e., radial EF (REF)] (with a mean of 23.0 ± 4.5% vs. 19.3 ± 4.2%), with other RV motion components remaining unchanged. The post-competition decrease in REF was more evident in runners with larger total volume of trainings (R2 = 0.4776, p = 0.0002) and higher concentrations of high-sensitivity cardiac troponin I (r = 0.43, p < 0.05) during the preparation period. The decrease in REF was more prominent in the training of marathoners more than 47 km/week. At stage II, marathoners with a more marked decrease in RVEF and REF had higher galectin-3 (Gal-3) levels (r = −0.48 and r = −0.39, respectively; p < 0.05). Running a marathon significantly altered the RV performance of amateur athletes. Transient impairment in RV systolic function resulted from decreased radial shortening, which appeared in those who trained more extensively. Observed ECHO changes correlated with the concentrations of the profibrotic marker Gal-3.

Adding historical high-sensitivity troponin T results to rule out acute myocardial infarction.

The clinical usefulness of historical concentrations of high-sensitivity cardiac troponin T (hs-cTnT) is unknown. This study investigated the ability to rule out myocardial infarction (MI) with the use of historical hs-cTnT concentrations among patients with chest pain in the emergency department (ED). The derivation cohort consisted of patients presenting with chest pain to nine different EDs (n = 60 071), where we included those with ≥1 hs-cTnT analysed at the index visit and ≥1 hs-cTnT results prior to the visit. We developed an algorithm to rule out MI within 30 days with a pre-specified target negative predictive value (NPV) of ≥99.5%. The performance was then validated in a separate cohort of ED chest pain patients (n = 10 994). A historical hs-cTnT < 12 ng/L and a < 3 ng/L absolute change between the historical and the index visit hs-cTnT had the best performance and ruled out 24 862 (41%) patients in the derivation cohort. In the validation cohort, these criteria identified 4764 (43%) low-risk patients in whom 18 (0.4%) MIs within 30 days occurred, and had an NPV for MI of 99.6% (99.4-99.8), a sensitivity of 96.9% (95.2-.2), and an LR- of 0.11 (0.07-0.14). Combining a historical hs-cTnT with a single new hs-cTnT may safely rule out MI and thereby reduce the need for serial hs-cTnT measurements in ED patients with chest pain.

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

Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data

BackgroundHigher body mass index (BMI) is associated with better outcome compared with normal weight in patients with HF and other chronic diseases. It remains uncertain whether the apparent protective role of obesity relates to the absence of comorbidities. Therefore, we investigated the effect of BMI on outcome in younger patients without co-morbidities as compared to older patients with co-morbidities in a large heart failure (HF) population.MethodsIn an individual patient data analysis from pooled cohorts, 5,819 patients with chronic HF and data available on BMI, co-morbidities and outcome were analysed. Patients were divided into four groups based on BMI (i.e. ≤ 18.5 kg/m2, 18.5–25.0 kg/m2; 25.0–30.0 kg/m2; 30.0 kg/m2). Primary endpoints included all-cause mortality and HF hospitalization-free survival.ResultsMean age was 65 ± 12 years, with a majority of males (78%), ischaemic HF and HF with reduced ejection fraction. Frequency of all-cause mortality or HF hospitalization was significantly worse in the lowest two BMI groups as compared to the other two groups; however, this effect was only seen in patients older than 75 years or having at least one relevant co-morbidity, and not in younger patients with HF only. After including medications and N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin concentrations into the model, the prognostic impact of BMI was largely absent even in the elderly group with co-morbidity.ConclusionsThe present study suggests that obesity is a marker of less advanced disease, but does not have an independent protective effect in patients with chronic HF.Graphic abstractCategories of BMI are only predictive of poor outcome in patients aged > 75 years or with at least one co-morbidity (bottom), but not in those aged < 75 years without co-morbidities (top). The prognostic effect largely disappears in multivariable analyses even for the former group. These findings question the protective effect of obesity in chronic heart failure (HF).

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

BackgroundDetailed insights in temporal evolution of high‐sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post‐ACS kinetics of high‐sensitivity cardiac troponin I (hs‐cTnI) and high‐sensitivity cardiac troponin T (hs‐cTnT), and to determine their intra‐ and interindividual variation in clinically stable patients.Methods and ResultsWe determined hs‐cTnI (Abbott) and hs‐cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1‐year follow‐up. Post‐ACS kinetics were studied by linear mixed‐effect models. Using the samples collected in the 6‐ to 12‐month post‐ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs‐cTnI and average hs‐cTnT concentration, and the intra‐ and interindividual variation for both biomarkers. Compared with hs‐cTnT, hs‐cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P<0.001) and was quicker below the biomarker‐specific upper reference limit (16 versus 19 days; P<0.001). In the post–6‐month samples, hs‐cTnI and hs‐cTnT showed modest correlation (r spearman=0.60), whereas the average hs‐cTnT concentration was 5 times more likely to be above the upper reference limit than hs‐cTnI. The intraindividual variations of hs‐cTnI and hs‐cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%.ConclusionsHs‐cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post–6‐month samples, hs‐cTnI and hs‐cTnT were clearly not interchangeable, and average hs‐cTnT concentrations were much more often above the upper reference limit than hs‐cTnI. For both markers, the within‐patient variation fell largely below beween‐patient variation.RegistrationURL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.

High-sensitivity cardiac troponin concentrations at presentation in patients with ST-segment elevation myocardial infarction

Abstract Background The widespread adoption of high-sensitivity cardiac troponin testing has encouraged the use of pathways to accelerate the rule-out and rule-in myocardial infarction in the Emergency Department. These pathways are not recommended for patients with ST-segment elevation, but there is a risk they may be applied incorrectly given that interpretation of the electrocardiogram is subjective, dependent on experience, and signs may be masked in those with posterior myocardial infarction. Methods Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge cluster randomized controlled trial across ten hospitals in Scotland. The index diagnosis was adjudicated two clinicians independently in all patients with high-sensitivity cardiac troponin I concentrations above the sex-specific 99th centile on serial testing and abnormalities on the electrocardiogram recorded. The proportion of patients with ST-segment elevation myocardial infarction and concentrations below the rule-out threshold (&amp;lt;5 ng/L), 99th centile (&amp;lt;16 ng/L and &amp;lt;34 ng/L for women and men) and rule-in threshold (&amp;lt;52 ng/L) at presentation were determined. Results In total 48,282 patients were recruited between June 2013, and March 2016 of which 22% (10,360/48,282) had peak cardiac troponin concentrations above the 99th centile. The adjudicated diagnosis was type 1 myocardial infarction in 55% (4,981/9,115) of patients and 10% (925/9,115) had ST-segment elevation myocardial infarction (age 65 [14] years, 68% men). The majority presented within 6 hours of symptom onset (67%, 619/925), and 84% (772/925) had cardiac troponin concentrations above the 99th centile at presentation. However, troponin concentrations were below the rule-out threshold in 2% (20/925) and the rule-in threshold in 26% (240/925) of patients with ST-segment elevation myocardial infarction. Discussion In patients with suspected acute coronary syndrome who have a final diagnosis of ST-segment elevation myocardial infarction, high-sensitivity cardiac troponin concentrations are below the rule-out and rule-in threshold at presentation in 1 in 50 and 1 in 4 patients, respectively. Clinicians should not rely on cardiac troponin concentrations to guide initial treatment decisions in patients with possible ST-segment elevation myocardial infarction. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). University hospital. 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). Data were generated in a large single-center diagnostic study using central adjudication. In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.

Causes of death in relation to stable troponin levels including chronic myocardial injury

BackgroundMany patients presenting with chest pain in the emergency department have stable concentrations of high-sensitivity cardiac troponin T (hs-cTnT) without any acute medical condition. Stable hs-cTnT levels are associated with a high risk of death. This study aimed to investigate causes of death in relation to hs-cTnT concentrations. MethodsIn a cohort of 19,460 patients with chest pain and stable hs-cTnT levels measured 2011–2014, of whom 1528 (7.9%) had chronic myocardial injury, we included all patients who died during follow-up (4.0 ± 1.3 years). Rates of cause-specific death were calculated for hs-cTnT concentrations and adjusted odds ratios (OR) estimated for causes of death at hs-cTnT 5–14 ng/l and >14 ng/l (referent hs-cTnT < 5 ng/l). ResultsThe study cohort comprised 1577 patients (8.1%), of whom 684 (43%) had chronic myocardial injury (hs-cTnT > 14 ng/l). Annual cardiovascular and non-cardiovascular death rates increased with increasing hs-cTnT from 0.07% and 0.4% (<5 ng/l) to 17% and 15% (≥50 ng/l), respectively. The ratio of cardiovascular to non-cardiovascular death increased with higher hs-cTnT. Patients with hs-cTnT 5–14 ng/l were 87% more likely to die from cardiovascular causes than those with hs-cTnT < 5 ng/l (adjusted OR: 1.87, 95% CI: 1.24–2.80). The association was similar for patients with chronic myocardial injury. ConclusionsHs-cTnT concentrations of 5–14 ng/l and >14 ng/l are associated with an almost twofold risk of cardiovascular death, whereas cardiovascular death almost never occurs in patients with undetectable troponin. Only with hs-cTnT concentrations ≥ 50 ng/l were cardiovascular diseases the predominant cause of death.

P3598Cardiac Cycle - The effect of exercise on cardiac troponin release

Abstract Introduction International guidelines recommend the use of low concentrations of high-sensitivity cardiac troponin to risk stratify patients with suspected acute coronary syndrome, however, troponin concentration may also rise due to physical exercise. Interpreting cardiac troponin concentration in this context is challenging because the magnitude and duration of troponin elevation following physical exercise is uncertain. Purpose To determine the effect of intensity and duration of physical exercise on cardiac troponin concentration. Methods We invited 10 physically active healthy volunteers (7 male and 3 female; mean age: 34±7) to attend 3 study visits, during which they underwent exercise on a stationary bicycle at prespecified intensities and durations. The first visit involved low intensity cycling (50–60% of the participant's lactate threshold [LT]) for 60 minutes. During the second visit, participants cycled at high intensity (80–90% LT) for 60 minutes and during the third study visit, participants cycled at moderate intensity (60–70% LT) for 4 hours. High-sensitivity cardiac troponin I (hs-cTnI) concentration was measured at the start of exercise and every hour up to 6 hours during each study visit and subsequently at 1, 2 and 7 days after each exercise visit. Results Study participants had a median hs-cTnI concentration of 1.8 ng/L (interquartile range [IQR] 0.8–5.7 ng/L) at baseline. Cardiac troponin concentration was elevated following moderate- and high-intensity exercise (P=0.006 and P&lt;0.001, respectively) but not following low-intensity exercise (P=0.137). Troponin concentrations were significantly higher following the shorter duration of high-intensity exercise (peak hs-cTnI concentration = 13 ng/L [IQR 6.5–27.1 ng/L]) compared to the longer duration moderate-intensity exercise (peak hs-cTnI concentration = 6.9 ng/L [2.9–7.9 ng/L]; P-value &lt;0.001). Following both moderate- and high-intensity exercise, cardiac troponin concentration returned to baseline within 48 hours (Figure 1). Troponin concentrations ng/L / time Conclusions Our study suggests that elevation in cardiac troponin concentration is associated with the intensity rather than duration of physical exercise, and that exercise-induced troponin elevations resolve within 48 hours. These findings have important implications for the interpretation of cardiac troponin in the risk stratification and diagnosis of patients who present with symptoms suggestive of acute coronary syndrome following physical exercise. Acknowledgement/Funding British Heart Foundation

Cardiac and Inflammatory Biomarkers Are Associated with Worsening Renal Outcomes in Patients with Type 2 Diabetes Mellitus: Observations from SAVOR-TIMI 53.

Cardiac and renal diseases commonly occur with bidirectional interactions. We hypothesized that cardiac and inflammatory biomarkers may assist in identification of patients with type 2 diabetes mellitus (T2DM) at high risk of worsening renal function. In this exploratory analysis from SAVOR-TIMI 53, concentrations of high-sensitivity cardiac troponin T (hs-TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP) were measured in baseline serum samples of 12310 patients. The primary end point for this analysis was a ≥40% decrease in estimated glomerular filtration rate (eGFR) at end of treatment (EOT) at a median of 2.1 years. The relationships between biomarkers and the end point were modeled using adjusted logistic and Cox regression. After multivariable adjustment including baseline renal function, each biomarker was independently associated with an increased risk of ≥40% decrease in eGFR at EOT [Quartile (Q) Q4 vs Q1: hs-TnT adjusted odds ratio (OR), 5.63 (3.49-9.10); NT-proBNP adjusted OR, 3.53 (2.29-5.45); hs-CRP adjusted OR, 1.84 (95% CI, 1.27-2.68); all P values ≤0.001]. Furthermore, each biomarker was independently associated with higher risk of worsening of urinary albumin-to-creatinine ratio (UACR) category (all P values ≤0.002). Sensitivity analyses in patients without heart failure and eGFR >60 mL/min provided similar results. In an adjusted multimarker model, hs-TnT and NT-proBNP remained significantly associated with both renal outcomes (all P values <0.01). hs-TnT, NT-proBNP, and hs-CRP were each associated with worsening of renal function [reduction in eGFR (≥40%) and deterioration in UACR class] in high-risk patients with T2DM. Patients with high cardiac or inflammatory biomarkers should be treated not only for their risk of cardiovascular outcomes but also followed for renal deterioration.