Changes In High-sensitivity Troponin Research Articles

Diagnostic potential of relative changes in high-sensitivity troponin levels during intracoronary acetylcholine provocation testing

Abstract Background Intracoronary acetylcholine (ACh) provocation testing is useful for the diagnosis of vasospastic angina (VSA). However, the positive or negative diagnosis of ACh testing is often challenging when lacking typical anginal symptoms and electrocardiographic changes during provocation tests. We hypothesized that relative changes in cardiac troponin levels during ACh provocation testing may be suggestive of myocardial ischemia and would be helpful for the VSA diagnosis. Purpose To evaluate the diagnostic potential of relative changes in high sensitivity troponin I (hs-TnI) levels during intracoronary ACh provocation test. Methods This preliminary study included a total of 29 patients undergoing invasive coronary angiography with or without ACh provocation tests. Patients were divided into three groups; no ACh provocation tests (i.e. angiography alone), negative ACh tests, and positive ACh tests. Blood samples were obtained twice, before and after angiography, through the arterial sheath to evaluate hs-TnI. The primary measure was relative changes in hs-TnI (i.e. Δhs-TnI). Positive ACh provocation test was defined as total or subtotal coronary occlusion accompanied by chest pain and/or ischemic electrocardiographic changes. Results Of the 29 patients, 10 (34.5%) underwent coronary angiography alone, while ACh provocation testing was performed in 19 (65.5%) patients, of whom 7 (36.8%) and 12 (63.2%) had negative and positive ACh test results. Overall, the mean time interval between the blood sample collections was 76 minutes. Levels of hs-TnI before angiography did not differ significantly in the no, negative, and positive ACh test groups (5.3 [2.8, 8.6] vs. 2.9 [1.3, 8.8] vs. 3.3 [1.6, 8.5] pg/ml, p=0.76), while Δhs-TnI was highest in the positive ACh test group, followed by the negative and no ACh test groups (4.2 [0.5, 8.1] vs. 0.8 [0.4, 4.6] vs. −0.3 [−0.6, 0.3], p=0.002) (Figure). Conclusions In patients undergoing intracoronary ACh testing for the VSA diagnosis, a relative increase in Δhs-TnI during angiography was observed than in those who did not undergo the provocation tests, particularly when the ACh test diagnosis was positive. Our findings suggest that Δhs-TnI has the potential to aid in the positive or negative diagnosis of ACh provocation testing.

External validation of a stepwise 0/1/3h algorithm to triage patients with suspected myocardial infarction

Abstract Background In patients with suspected myocardial infarction (MI), application of 0/1h-algorithms is recommended by guidelines of the European Society of Cardiology. Depending on assay-specific changes of high-sensitivity troponin (hs-Tn), these algorithms allow for rule-in or rule-out of MI at presentation or after 1 hour (h). Yet, a relevant proportion of patients remain in the observe group at 1h in need for further diagnostic. Recently, specific cutoffs at 3h were suggested for hs-TnT, enabling an additional 3h triage option in conjunction with the 0/1h algorithm to further reduce the proportion of patients in the observe zone. Objective We aimed to externally validate the diagnostic performance of the 0/1/3h algorithm in patients with suspected MI. Methods We consecutively enrolled patients with symptoms suggestive of MI in the emergency department of a tertiary hospital in Germany. Patients with STEMI were excluded. Concentrations of hs-TnT were measured at presentation, after 1h and 3h. Final diagnoses were adjudicated by two cardiologists according to the 4th Universal Definition of MI. Applying the 0/1/3h algorithm, patients were triaged into rule-in, rule-out- and observe-group. We assessed the diagnostic performance parameters in the overall sample as well as for predefined subgroups including sex, age ≥65 vs. <65 years, glomerular filtration rate (GFR) ≥60ml/min/m² vs. <60ml/min/m², and symptom onset time <1h vs. 1-3h vs. >3h). Results In 2,514 patients (median age 64 years, 36.4% female), prevalence of NSTEMI was 14.4%. Application of the 0/1/3h algorithm ruled-out 1511 (60.1%) and ruled-in 587 (23.3%) patients. Only 416 (16.6%) remained in the observe group at 3h. Safety of rule-out was high with a sensitivity of 98.6% (95%CI 96.8%, 99.4%) and a corresponding negative predictive value of 99.7% (95%CI 99.2%, 99.9%). Rule-in performance was acceptable with a specificity of 89.3% (95%CI 87.9%, 90.5%) and positive predictive value (PPV) of 60.8% (95%CI 56.8, 64.7, Figure 1). Regarding subgroup analyses, sensitivity and NPV were marginally but statistically lower in patients with normal as compared with impaired renal function (p both <0.001). Further, specificity was substantially lower in older patients (84.8% vs. 93.3%, p<0.001), patients with GFR<60ml/min/m² (78.3% vs. 93.0%, p<0.001) as well as in male patients (88.1% vs. 91.2%, p=0.028) (Figure 2). A relevantly larger proportion of patients remained in the observe group after 3h in patients with impaired renal function (32.3% vs. 10.9%), as well as in patients aged ≥ 65 years (26.8% vs. 6.8%). Conclusion Application of the 0/1/3h algorithm in patients with suspected MI resulted in good diagnostic performance with excellent rule-out safety and moderate rule-in capacity. In patients with impaired renal function as well as elderly patients, specificity was significantly lower while observing a larger proportion of patients remaining in the observe zone at three hours.Figure 1:Diagnostic flowFigure 2:Forest Plots

Non-Invasive Ultrasound Therapy for Severe Aortic Stenosis: Early Effects on the Valve, Ventricle, and Cardiac Biomarkers (A Case Series).

Background: Transcatheter aortic valve replacement (TAVR) was developed for inoperable patients with severe aortic stenosis. However, despite TAVR advancements, some patients remain untreated due to complex comorbidities, necessitating less-invasive approaches. Non-invasive ultrasound therapy (NIUT), a new treatment modality, has the potential to address this treatment gap, delivering short ultrasound pulses that create cavitation bubble clouds, aimed at softening embedded calcification in stiffened valve tissue. Methods: In the prospective Valvosoft® Serbian first-in-human study, we assessed the safety and efficacy of NIUT and its impact on aortic valve hemodynamics, on the left ventricle, and on systemic inflammation in patients with severe symptomatic aortic stenosis not eligible for TAVR or surgery. Results: Ten patients were included. Significant improvements were observed in hemodynamic parameters from baseline to one month, including a 39% increase in the aortic valve area (from 0.5 cm2 to 0.7 cm2, p = 0.001) and a 23% decrease in the mean transvalvular gradient (from 54 mmHg to 38 mmHg, p = 0.01). Additionally, left ventricular global longitudinal strain significantly rose, while global wasted work significantly declined at one month. A dose-response relationship was observed between treatment parameters (peak acoustic power, intensity spatial-peak pulse-average, and mean acoustic energy) and hemodynamic outcomes. NIUT was safely applied, with no clinically relevant changes in high-sensitivity troponin T or C-reactive protein and with a numerical, but not statistically significant, reduction in brain natriuretic peptide (from 471 pg/mL at baseline to 251 pg/mL at one month). Conclusions: This first-in-human study demonstrates that NIUT is safe and confers statistically significant hemodynamic benefits both on the valve and ventricle.

Supervised exercise training in patients with cancer during anthracycline-based chemotherapy to mitigate cardiotoxicity: a randomized-controlled-trial.

Exercise training (ET) has been shown to mitigate cardiotoxicity of anthracycline-based chemotherapies (AC) in animal models. Data from randomized controlled trials in patients with cancer are sparse. Patients with breast cancer or lymphoma receiving AC were recruited from four cancer centres and randomly assigned to 3 months supervised ET. Primary outcome was change in left ventricular global longitudinal strain (GLS) from baseline (before AC) to post AC (AC-end) compared between the EXduringAC group, who participated in an exercise intervention during AC including the provision of an activity tracker, and the control group EXpostAC, who received an activity tracker only. Secondary outcome parameters were changes in high sensitivity Troponin T (hsTnT), NT-pro-brain natriuretic peptide (NT-proBNP), peak oxygen consumption (peak VO2) and objectively measured physical activity (PA) during this same time-period. All assessments were repeated at a 12-week follow-up from AC-end, when also the EXpostAC group had completed the ET, that started after AC. In exploratory analyses, robust linear models were performed to assess the association of PA with changes in echocardiographic parameters and biomarkers of LV function. Fifty-seven patients (median age 47 years; 95% women) were randomized to EXduringAC (n = 28) and EXpostAC (n = 29) group. At AC-end, GLS deteriorated in both study groups (albeit insignificantly) with 7.4% and 1.0% in EXduringAC (n = 18) and EXpostAC (n = 18), respectively, and hsTnT and NT-proBNP significantly increased in both groups, without difference between groups for any parameter. Change in peak VO2 (-1.0 and -1.1 ml/kg/min) at AC-end was also similar between groups as was duration of moderate-to-vigorous PA (MVPA) with a median of 33 [26, 47] min/day and 32 [21, 59] min/day in the EXduringAC and EXpostAC group, respectively. In the robust linear model including the pooled patient population, MVPA was significantly associated with a more negative GLS and lesser increase in hsTnT at AC-end. In this small scale RCT, supervised ET during AC was not superior to wearing a PA tracker to mitigate cardiotoxicity. The dose-response relationship between PA and cardioprotective effects during AC found in our and previous data supports the notion that PA should be recommended to patients undergoing AC. ClinicalTrials.gov, identifier NCT03850171.

Abstract 18587: Factors Associated With Changes in High Sensitivity Troponin and NT-proBNP in Response to Intensive Blood Pressure Lowering in SPRINT

Background We have recently shown that intensive SBP lowering was associated with a modest increase in hscTnT and a decrease in NT-proBNP. In the present study, we sought to compare the independent determinants of changes in biomarkers in intensive vs. standard SBP lowering in SPRINT. Methods: Hs-cTnT and NT- proBNP were measured at baseline, 1-year, and 2-year from stored specimens. Biomarker changes were analyzed according to categories (≥50% increase, ≥50% decrease, and <50% change). The impact of intensive SBP lowering on changes in biomarkers levels was assessed using multivariable-adjusted multinomial logistic regression models in standard and intensive SBP lowering separately. Results: Of 9,361 SPRINT participants, we measured cTnT and NT-proBNP in 8,828 (baseline), 7,887 (year 1), and 7,463 (year 2) free of CVD events. Among individuals with detectable hscTnT at baseline (≥6 ng/L), a 50% increase in hscTnT was observed in 4.5% (year 1) and 6.7% (year 2). Among individuals with baseline NT-proBNP ≥125 pg/mL, a 50% increase in NT-proBNP was observed in 16.7% (year 1) and 21.1% (year 2). Overall, a similar pattern of associations was observed with both biomarkers across treatment groups (see Figure). Several exceptions were noted. Prevalent CVD was associated with an increase in both NT-proBNP and hscTnT in the standard SBP lowering arm but not in the intensive SBP lowering arm. Higher baseline hscTnT was associated with an increase in hscTnT only in the standard arm. Furthermore, we observed biomarker-specific differences. For example, white race, female sex, and blood pressure were consistently associated with an increase in NT-proBNP. In contrast, declining renal function and male sex were associated with increasing hscTnT. Conclusion Factors associated with changes in biomarkers varied by treatment assignment and between biomarkers. These findings highlight the role of noncardiac factors on biomarker changes in the context of intensive SBP lowering.

Release of neuronal injury markers differs according to the technique of pulmonary vein isolation

Abstract Funding Acknowledgements Type of funding sources: None. Background Previous studies showed a release of neuronal injury markers during catheter ablation of atrial fibrillation using thermal energies such as radiofrequency or cryothermy. Pulsed field ablation (PFA), that is characterized by its tissue specificity, serves as an innovative technique for pulmonary vein isolation (PVI). Purpose To investigate the amount of neuronal injury marker release in patients undergoing first PVI using different ablation modalities. Methods We included 65 consecutive patients (age 69 ± 11 years, 52% females) that underwent PVI for the first time with either radiofrequency using standard ablation settings (RF; n = 11), radiofrequency with high-power short-duration (HPSD; n = 32) or PFA (PFA; n = 17) for atrial fibrillation. Protein S100B levels and Neuron-specific enolase (NSE) in coronary sinus blood were detected before and after PVI. The release of neuronal injury markers was assessed according to the ablation technique used. Results The change in high-sensitivity troponin (hsTnT) levels was similar in all groups (RF: Δ175.6±181.9 ng/l; HPSD: Δ153.1±233.5 ng/l; PFA: Δ181.1±257.6 ng/l; p=0.632). NSE was significantly released only in patients treated with PFA-PVI (25.2±13.4 to 45.2±24.9 ng/ml; p<0.001), but not in patients treated with RF-PVI or HPSD-PVI (both p>0.05). S100B was released in patients treated with RF-PVI (79.7±32.2 to 118.6±46.4 pg/ml; p=0.006) and PVI-PFA (80.6±38.1 to 138.1±82.7 pg/ml; p=0.002) after the procedure, while there was only a numerically increase in patients treated with PVI-HPSD (88.6±38.7 to 109.1±54.2 pg/ml; p=0.172). We detected no correlation between the release of neuronal biomarkers (Δ NSE and Δ S100B) and cardiac damage (Δ hsTnT) (all p>0.05). The ΔNSE/ΔhsTnT ratio (p<0.001), and the ΔS100B/ΔhsTnT ratio (p=0.002) was higher in patients undergoing PFA-PVI (ΔNSE/ΔhsTnT 0.19±0.20; ΔS100B/ΔhsTnT 0.75±1.35), than in patients undergoing RF-PVI (ΔNSE/ΔhsTnT 0.0±0.06; ΔS100B/ΔhsTnT 0.35±0.32) and HPSD-PVI (ΔNSE/ΔhsTnT 0.04±0.11; ΔS100B/ΔhsTnT 0.13±1.55). Conclusion The release of neuronal injury markers differs according to the technique used for PVI. Patients treated with PFA showed a higher release of neuronal injury markers compared to radiofrequency ablation, that was not explained by more myocardial damage. Future research needs to investigate the prognostic relevance in terms of atrial fibrillation recurrence of the neural injury induced by PFA compared to radiofrequency PVI.

The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer; however, at the potential cost of serious adverse events including cardiac injury. To assess the baseline and longitudinal changes in high sensitivity-Troponin (hs-Tn) in patients treated with pembrolizumab as a potential predictor for the development of major adverse cardiac events (MACE) and survival. We performed a retrospective analysis of cancer patients treated with pembrolizumab at our center. All participants had baseline measurements of hs-TnI prior to initiation of pembrolizumab (T1), with half of the patients performing follow-up measurements at their second encounter for therapy introduction (T2). We first evaluated the prevalence of abnormally elevated serum hs-TnI (> 50nanogram per liter) at T1 and T2. We then evaluated the predictive value of abnormal levels at T1 or T2 in relation to the development of MACE (composite outcomes of myocarditis, acute coronary syndrome, heart failure, venous thromboembolism, cardiovascular hospitalization and cardiovascular mortality) and all-cause mortality. Among 135 patients, the mean age was 72years, predominantly male (61%). Abnormally elevated hs-TnI at T1 was observed in 7 (5%) patients and emerged as a significant independent predictor for MACE (HR 8.1, 95% CI 1.67-37.4, p = 0.009) and all-cause mortality (HR 5.37, 95% CI 2.1-13.57, p < 0.001). Abnormally elevated hs-TnI at T2 was observed in 8 (11%) patients and emerged as a significant independent predictor for MACE (HR 10.49, 95% CI 1.68-65.5, p = 0.009), but not for mortality (p = 0.200). Abnormally elevated baseline and follow-up hs-TnI served as significant independent predictors for MACE, with an increased risk of development being 8-tenfold. Furthermore, elevated baseline hs-TnI showed a predictive value for all-cause mortality. Central illustration: Novel immune checkpoint inhibitor (ICIs) therapy has been found to revolutionize cancer therapy through increased activation of host immune systems to target and reduce tumor burden, but may come at the cost of serious adverse cardiac events. Identification of early biomarkers for the prediction and detection of these events is necessary.

Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome

Studies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population. To evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS). This is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022. The outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses. Of 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change. Among stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population. ClinicalTrials.gov Identifier: NCT00202878.

Changes in high-sensitivity troponin according to optical characteristics of neointima and treatment modality of in-stent restenosis

Abstract Background Intravascular imaging studies of native vessel percutaneous coronary intervention (PCI) have shown a relationship between presence of lipid-rich plaques or large necrotic cores and occurrence of periprocedural myocardial injury (PMI). However, limited evidence exists on the relationship between neointimal tissue characteristics, and PMI following PCI of in-stent restenosis (ISR) lesions. Beside neointimal tissue characteristics, treatment modality may represent an additional mechanism influencing PMI in the setting of ISR-PCI. Current ESC guidelines recommend either drug-coated balloon (DCB) or drug-eluting stent (DES) as treatment options for ISR. Purpose To investigate the impact of increasing neointimal inhomogeneity and neoatherosclerotic changes of the neointima, as well as of ISR treatment modality on the occurrence of PMI. Methods Patients with normal or stable/falling increased baseline high-sensitivity troponin T (hs-cTnT) undergoing intravascular optical coherence tomography (OCT) and subsequent DCB or DES treatment of ISR lesions were included. PMI was classified as “minor” or “major” according to the definitions of a recent ESC/EAPCI consensus document. Quadrant-based neointimal characterization was performed at the frame displaying the maximal % area stenosis and the 5 preceding and following analyzed frames. Neointimal tissue was categorized as homogeneous or inhomogeneous, the latter including heterogeneous, layered or neoatherosclerosis quadrants. Hs-cTnT was measured at the time of admission, 3–6 h after PCI, at 6 h intervals in case of rising values, and on a daily basis thereafter. Results Overall, 128 patients were subdivided into low (n=64) and high (n=64) neointimal inhomogeneity groups, based on the median of distribution of non-homogeneous quadrants. No significant between-group differences were detected in terms of hs-cTnT changes (28.0 [12.0–65.8] vs. 25.5 [9.8–65.0] ng/L; p=0.355), or major PMI occurrence (31.2% vs. 31.2%; p=1.000). Similarly, no differences were observed between DCB and DES treated groups in terms of hs-cTnT changes (27.0 [10.0–64.0] vs. 28.0 [11.0–73.0] ng/L; p=0.795), or occurrence of major PMI (28.9% vs. 35.6%; p=0.566). Of note, no significant interaction was observed between optical neointimal characteristics and treatment modality in terms of changes in hs-cTnT (p int = 0.432). There were no significant differences in PMI occurrence between low and high neoatherosclerosis subgroups. Conclusion The present study, which combined a detailed, quadrant-based multi-frame neointimal characterization coupled to systematic pre- and post-procedural hs-cTnT measurements in patients undergoing PCI for ISR, showed no association between increasing neointimal inhomogeneity, or increasing expression of neoatherosclerosis, and occurrence of PMI. PMI occurrence was not influenced by the ISR treatment modality (DCB vs. DES), a finding that supports the safety of DCB treatment for ISR. Funding Acknowledgement Type of funding sources: None.

376 Dynamic Changes in High Sensitivity Troponin T Are Associated With Increased Sepsis Mortality

Elevated serum cardiac troponin is a marker of myocardial injury associated with increased mortality in sepsis. Increasing use of high sensitivity troponin T (hsTrop) in the emergency department (ED) has allowed earlier and more sensitive detection of myocardial injury in acute coronary syndromes but has yet to be studied in relation to sepsis. The objective of this study was to determine the association between hsTrop changes and mortality in sepsis. This was a retrospective cohort study performed at a single, tertiary academic center. A concurrent multicenter sepsis trial was being conducted during the study period (June 1st, 2018 and March 20th, 2020) and the cohort for this study was derived from the screening log of this unrelated study. Adult patients with a suspected infection and hypotension after 1 liter of crystalloid fluids were included. All data were collected via direct database query to the electronic health record. hsTrop was measured in the ED and again approximately 2 hours later. The difference (delta) between the second and first measurements was the primary exposure and treated as a 4- level categorical variable (delta >6 ng/L, - 6 > delta > 6, delta <- 6 and no delta obtained). The primary outcome was 28- day mortality and secondary outcomes included mechanical ventilation, use of vasopressors, and crystalloid fluid received. Inverse probability weighting (IPW) was used to weight covariates for the probability of obtaining a hsTrop delta measurement in the ED. Using IPW derived weights, a multivariable logistic regression model was used to determine the association between hsTrop delta and 28- day mortality. Descriptive statistics and univariate analyses were also performed. After exclusion of clinician suspected baseline hypotension or hypotension not due to sepsis cause, as well as non- sepsis causes of hsTrop delta, 763 patients met the inclusion and exclusion criteria. 48 had a delta > 6 ng/L, 54 had a delta < - 6 ng/L, 175 had a delta between - 6 and 6, and 486 had no hsTrop delta obtained in the ED. Patients who had a hsTrop testing skewed male, older and with history of renal, heart disease or with chief complaints of chest pain or shortness of breath. In the weighted multivariable analysis and after adjustment for sex, age, and Charlson comorbidity index, both an hsTrop delta > 6 (OR 3.4 [95% CI 1.7 - 7.2]) and delta < - 6 (OR 2.2 [95% CI 1.1 - 4.4]) were associated with increased mortality at 28 days. The hsTrop delta >6 group was also associated with an increased risk for early mechanical ventilation (HR 3.0 [95% CI 1.8 - 4.9]), use of vasopressors (OR 3.7 [95% CI 2.0 - 7.0]), and increased crystalloid fluids administered during the first 24 hours (mean 4060 mL vs. ∼ 3000 mL for all other groups, p = 0.01). Dynamic changes in hsTrop obtained at ED presentation are associated with increased mortality in sepsis. Both an increasing and decreasing hsTrop delta are associated with a higher risk for 28- day mortality. This study was limited by its retrospective and single site design. Future studies are required to determine how hsTrop can be used to modify treatment.

Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications.

Cardiac troponin T determination plays a dominant role in diagnosis of myocardial pathologies. Despite generally accepted use of high-sensitive cardiac troponin T assays (hscTnT) and clearly defined cut-off limit in adults, the uncertainty persists in infants. The aim of this study was to assess plasmatic concentrations of hscTnT and describe sequential age-related dynamic changes of hscTnT in healthy infants and toddlers. Seventy-eight children (52 males/26 females) from Czech Republic aged 44 to 872 days (median, interquartile range 271; 126 to 486 days) were consecutively enrolled in the single-center, prospective observational study. Plasma concentrations of hscTnT were analyzed by the electrochemiluminescent method, age-related reference intervals were calculated using the polynominal regression model. Amongst the study population (n=78), the upper limit of hscTnT concentration defined as the 99th percentile was calculated. The 99th percentile with 95 % confidence interval at the end of 2nd, 3rd, 4th, 5th, 6th and 7th month of postnatal life were: 81 (40.6 to 63.6), 61 (36.0 to 55.3), 47 (31.9 to 48.3), 37 (28.1 to 42.3), 30 (24.7 to 37.2) and 25 (21.5 to 32.7) ng/l, respectively. Concentration of adults 99th percentile (14 ng/l) was achieved approximately at 1 year of postnatal life. Statistically significant negative correlation of hscTnT concentration with age (r=-0.81, p<0.001) was found. Significant gender differences were not found (p>0.07). The study revealed substantially increased reference intervals of hscTnT levels in infants when compared with adult population. Based on our preliminary results, the age-related interpretation of hscTnT plasmatic concentration is recommended.

Change in high-sensitivity troponin t levels and 1-year outcomes in patients with acute heart failure: China PEACE prospective heart failure study

Abstract Background High-sensitivity cardiac troponin T (hs-cTnT) is an important prognostic marker in heart failure (HF). However, it is unclear whether the change of hs-cTnT levels can predict long-term clinical outcomes in patients with acute HF. Purpose To examine the association between change in hs-cTnT from hospital admission to 1-month after discharge and subsequent 1-year cardiovascular death or HF hospitalization in patients with acute HF. Methods We included patients hospitalized primarily for HF from 52 hospitals in China, who had central analysis of hs-cTnT at both admission and 1-month after discharge. Change in hs-cTnT was calculated as hs-cTnT level at 1-month minors that at admission. The composite outcome measure was cardiovascular death or HF hospitalization within 1 year after discharge. We tested the linearity assumption between change in hs-cTnT level and the composite events using restricted cubic splines. To further explore the quantitative association between change in hs-cTNT and the events, we also applied a Cox proportional hazards model using change in hs-cTNT as a continuous variable, adjusting for hs-cTnT level at admission (log transformed) and known prognostic variables. Results We included 2355 patients hospitalized primarily for HF. Median change in hs-cTnT from baseline was −2.7ng/L (IQR −9 to 0.7). 614 (26.1%) patients experienced the events of cardiovascular death or HF hospitalization within 1 year. Among patients with hs-cTnT &amp;lt;14ng/L (the upper limit of the reference value) at admission, patients had low risk of the events regardless whether hs-cTNT ≥14ng/L at 1-month or not (20.2% vs. 14.1%, p=0.11). Among patients with hs-cTnT ≥14ng/L at admission, patients with hs-cTNT ≥14ng/L at 1-month had higher risk of the events than those with hs-cTnT &amp;lt;14ng/L (36.4% vs. 18.6%, p&amp;lt;0.0001). The association between change in hs-cTnT and the events was non-linear. When change in hs-cTnT was &amp;lt;4ng/L and &amp;gt;−4ng/L, per 1 ng/L decrease was associated with a 7% reduction in risk of the events [hazard ratio (HR) 0.93, 95% CI 0.88–0.99]. When change in hs-cTnT was &amp;lt;−4ng/L, there was a levelling off in the reduced risk (HR: 0.99, 95% CI 0.99–1.00). While change in hs-cTnT was &amp;gt;4ng/L, it was not significantly associated with the events any longer (Figure 1). Conclusion Among patients hospitalized for HF, changes in hs-cTnT from admission to 1 month can predict the risk of cardiovascular death and HF hospitalization. Funding Acknowledgement Type of funding source: Other. Main funding source(s): The National Key Research and Development Program from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science; the 111 Project from the Ministry of Education of China

Serial changes in high-sensitivity troponin I levels indicate poorer prognosis in patients with suspected acute coronary syndrome who fail to reach a level greater than the 99th percentile

Abstract Background According to the fourth universal definition of myocardial infarction (MI) consensus paper, patients with changing troponins who do not reach a concentration greater than the 99th percentile may still be at high risk and should be followed closely. Purpose To determine long-term prognostic implications of high-sensitivity troponin I (hs-TnI) levels and their relative change (Δ) from baseline in subjects with suspected acute coronary syndrome (ACS). Methods We conducted a retrospective cohort study through individual participant-level linkage between Danish national registries. Subjects with a final discharge diagnosis of acute MI, unstable angina, suspected MI, or chest pain from October 2013 through December 2016 who had a record of at least two serial hs-TnI (Dimension Vista®, Siemens Healthineers, Erlangen, Germany; 99th percentile: 45 ng/l) measurements during hospitalization comprised the study population. Kaplan-Meier analysis and multivariable Cox regression, incorporating the competing risk of death, were used to examine the prognostic implications of serial hs-TnI. Subjects were categorized according to whether their first and second hs-TnI were normal/elevated as well as Δhs-TnI and its direction, the latter using cut-offs for Δhs-TnI rises and/or falls of 20% and 50%, extrapolated from the recommendations for troponin T. The primary outcome was a composite of death from cardiovascular causes, recurrent MI, or repeat revascularization (i.e. not including the index event unless the patient died) at 12 months. Results A total of 14,514 individuals (mean age 62.2 years, 46.6% women) were included of whom 3407 (23.5%) had a final diagnosis of MI, 667 (4.6%) of unstable angina, and 10,440 (71.9%) of either suspected MI or chest pain. Median baseline hs-TnI was 15 ng/l (25.3% elevated), second hs-TnI 15 ng/l (29.4% elevated), Δhs-TnI 0%, and time between samples 6.2 hours. At 12 months, 909 (6.3%) first primary events had occurred. Baseline hs-TnI and Δhs-TnI both displayed a significant, non-linear association with the primary outcome (P&amp;lt;0.001). The Figure shows the prognostic implications of serial hs-TnI. Overall, subjects with two consecutively elevated hs-TnI had the highest 12-month event risk (15.7%), followed by those who went from a normal to an elevated hs-TnI (9.9%), those who went from an elevated to a normal hs-TnI (4.2%), and those with two normal hs-TnI (2.7%). Most either had no significant Δhs-TnI (−20% to 20%: 74.9%) or a large positive Δhs-TnI (&amp;gt;50%: 17.5%). Individuals with any Δhs-TnI (&amp;gt;20% in either direction) had a worse prognosis than those without. This was also true for the group of individuals with two normal hs-TnI (event risk 7.8% in those with a Δhs-TnI &amp;gt;20% versus 2.3% in those without, P&amp;lt;0.001). Conclusions Δhs-TnI was an important determinant of poorer prognosis in subjects with suspected ACS, even among individuals who did not reach a concentration greater than the 99th percentile. Figure 1 Funding Acknowledgement Type of funding source: None

CHANGES IN HIGH-SENSITIVITY TROPONIN AND THE RISK OF INCIDENT CARDIOVASCULAR EVENTS: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)

Few studies have examined the association between changes in high sensitivity troponin (hsTnT) and cardiovascular events in a multi-ethnic population. Participants from MESA who had hsTnT measured at Exams 1 (2000–02) and 3 (2004–05) were included and categorized as sustained undetectable (

Association of Longitudinal Change in High-Sensitivity Troponin with All-Cause Mortality in Coronary Artery Disease: The Heart and Soul Study

Background: Serial increases in high-sensitivity cardiac troponin (hs-cTnT) have been associated with death in community-dwelling adults, but the association remains uninvestigated in those with coronary artery disease (CAD). Methods: We measured hs-cTnT at baseline and after 5 years in 635 ambulatory Heart and Soul Study patients with CAD. We also performed echocardiography at rest and after treadmill exercise at baseline and after 5 years. Participants were subsequently followed for the outcome of death. We used a multivariable-adjusted Cox proportional hazards model to evaluate the association between 5-year change in hs-cTnT and subsequent all-cause mortality. Results: Of the 635 subjects, there were 386 participants (61%) who had an increase in hs-cTnT levels between baseline and year 5 measurements (median increase 5.6 pg/mL, IQR 3.2–9.9 pg/mL). There were 182 deaths after a mean 4.2-year follow-up after the year 5 visit. After adjusting for clinical variables, a >50% increase in hs-cTnT between baseline and year 5 was associated with a nearly 2-fold increased risk of death from any cause (hazard ratio 1.7, 95% confidence interval 1.1–2.7). When addition of year 5 hs-cTnT was compared to a model including clinical variables and baseline hs-cTnT, there was a modest but statistically significant increase in C-statistic from 0.82 to 0.83 (p = 0.04). Conclusion: In ambulatory patients with CAD, serial increases in hs-cTnT over time are associated with an increased risk of death.

P1733Dynamic changes of high-sensitivity troponin I after non-invasive stress-testing

Abstract Objective In patients with suspected coronary artery disease (CAD) and intermediate pretest probability non-invasive stress-testing is recommended in current guidelines. However, sensitivity and specificity of these tests are limited. We aimed to investigate the additional diagnostic value of high-sensitivity troponin I concentrations measured before and after stress-testing. Methods We included patients undergoing non-invasive stress-testing in a prospective cohort study. All patients provided written informed consent, were at least 18 years old and underwent either stress-echocardiography, stress-MRI or myocardial perfusion scintigraphy. Baseline parameters were collected by questionnaire and chart review. Blood samples were collected before, and one hour after the stress-test. Troponin was measured using the Abbott Architect high-sensitivity troponin I (hs-TnI) assay. The diagnostic performance to predict a pathological stress-test was evaluated by calculation of the area under the ROC curve (AUC) using baseline hs-TnI concentrations and the absolute change after one hour. An optimal cutoff was determined by maximization of the Youden Index. Univariate odds ratios (OR) were calculated to identify predictors for a pathological stress-test. Additionally ORs for the optimal hs-TnI cutoff were calculated in a multivarite regression with adjustment for baseline variables. Results In total 391 patients with a median age of 70 years were included. 66.8% were males, 83.4% had prevalent hypertension, 55.9% had dyslipidemia and 55.4% had a prior history of CAD. A pathological stress-test was reported in 21.5% and these patients had a higher cardiovascular risk profile, compared to patients with a non-pathological stress-test. The baseline hs-TnI concentrations were 4.7 ng/L in the overall population, 4.2 ng/L in patients with a non-pathological stress-test and 8.4 ng/L (p&lt;0.001) in patients with a pathological stress-test. There was no significant hs-TnI changes one hour after stress-testing. The AUC for the baseline hs-TnI was 0.65 and the optimal cutoff was determined at 7.7 ng/L. Most cardiovascular risk factors were predictors for a pathological stress-test. The OR for an elevated hs-TnI above the optimized cutoff was 3.34 (95% CI 2.03, 5.52). In a multivariate model a baseline hs-TnI above 7.7 ng/L showed an OR of 2.07 (95% CI 1.04, 4.12; p-value 0.039) Conclusion In patients undergoing non-invasive stress-testing, hs-TnI concentrations did not significantly change one hour after exercise. However, an elevated troponin concentration is an independent predictor for a pathological stress-test.

Chest pain with less than 20% change in high sensitivity troponin T - a low risk cohort?

Background: Patients with chest pain are risk-stratified using serial high-sensitivity troponin (T) assays (hsTnT). Those with change in (Δ)hsTnT <20% are often categorised as low-risk and are less likely to be managed as acute coronary syndromes (ACS). We sought to characterise such a population of ‘low-risk’ chest pain presenters.Methods: We performed a retrospective cohort analysis of sequential patients admitted to our centre over a 1-year period with chest pain, absence of ST-elevation, with elevated hsTnT concentrations, and compared demographic, clinical and outcome data according to ΔhsTnT.Results: Three hundred and eleven patients were subdivided by ΔhsTnT [<20% (n = 80), 20–100% (n = 78), >100% (n = 153)]. Baseline demographic data were well-matched across the three subgroups; atrial fibrillation was more common in the two lower magnitude ΔhsTnT groups. Obstructive coronary artery disease (CAD) – while less common in those with ΔhsTnT <20% (66.2%) compared to the 20–100% (73.1%) and >100% (75.9%) groups (p = 0.03) – remained high in this lower risk group, and indeed revascularisation occurred in >60% of patients, equally frequently in all three groups. Using absolute ΔhsTnT ≥9ng/L within the ΔhsTnT <20% group provided incremental value in ruling in ACS, with a positive predictive value of 74.1%. ΔhsTnT was a univariate but not a multivariate predictor of obstructive CAD.Conclusions: Obstructive CAD and need for revascularisation are frequent in chest pain presenters with ΔhsTnT <20%. The increasing focus on hsTnT algorithms to exclude ACS and promote early discharge without adequate clinical risk stratification modelling risks misdiagnosis of patients presenting with acute myocardial ischaemia with a low-level hsTnT rise.

Progressive myocardial injury is associated with mortality in the acute respiratory distress syndrome

PurposeMyocardial injury connotes worse prognosis in the Acute Respiratory Distress Syndrome (ARDS), however the prognostic connotation of changes in cardiac troponin (cTn) levels in ARDS patients is not known. MethodsWe performed a study of 908 ARDS patients enrolled in two previously completed ARDS Network trials. We obtained plasma samples via the NIH BIOLINCC repository and measured cTn using the ARCHITECT STAT high sensitivity troponin-I assay (Abbott Laboratories) at trial day 0 and 3. We constructed Cox proportional hazard models to determine the association between 60-day mortality and quintiles of percentage change in high-sensitivity troponin (ΔhsTnI). ResultsThe median percent change in hsTnI (%ΔhsTnI) from day 0 to day 3 was −58.2% (IQR -79.0 to 0%). After multivariable adjustment, participants with a 32.1% or greater increase in hsTnI between day 0 and day 3 (highest quintile) had a 2.27 fold increased risk for mortality (95% CI 1.29 – 3.99, p = 0.002) as well as fewer ventilator-free and ICU-free days compared to the lowest quintile. ConclusionProgressive myocardial injury in ARDS patients is associated with worse outcome, independent of severity of critical illness. Investigation of the mechanisms underlying this relationship is warranted to guide possible strategies to mitigate myocardial injury in ARDS.

Increased Rho kinase activity in patients with heart ischemia/reperfusion.

Rho kinase is a downstream effector of Rho GTPase that is known to regulate various pathological processes. The aim of this study was to evaluate the regulation of Rho kinase activity in leukocytes in patients with ischemia/reperfusion (I/R) injury. We investigated 38 patients with acute ST-segment elevation myocardial infarction (STEMI), 26 patients with atherosclerosis (AS) and 22 normal subjects. All patients underwent coronary angiography (CAG) and all STEMI patients received primary percutaneous coronary intervention (PPCI) of the left anterior descending artery (LAD) within 12 h after chest pain on-set. Blood samples for leukocyte Rho kinase activity were obtained before CAG and 3 and 24 hours after CAG/PCI. Rho kinase activity increased in the I/R and AS groups. Compared with the AS group, Rho kinase activity was significantly higher in peripheral blood leukocytes in STEMI/PPCI. Furthermore, there was no correlation between changes in Rho kinase activity and changes in high-sensitivity troponin I (hs-TnI) and C-reactive protein (CRP). There was a negative correlation between Rho kinase activity and IL-6. Rho kinase is involved in the pathogenesis of heart I/R injury in patients. Inhibition of Rho kinase may be an additional therapeutic intervention for the treatment of I/R.

Changes in high-sensitivity troponin after drug-coated balloon angioplasty for drug-eluting stent restenosis.

The success of drug-coated balloon therapy might be compromised by intraprocedural particulate embolisation of matrix coating, which may cause downstream microvascular obstruction. We aimed to investigate whether drug-coated balloon therapy was associated with an increase in markers of myocardial necrosis compared with drug-eluting stents or plain balloon angioplasty. In the ISAR-DESIRE-3 trial, patients with limus-eluting stent restenosis were randomised to treatment with a paclitaxel-coated balloon (PCB), paclitaxel-eluting stent (PES) or balloon angioplasty. We included enrolled patients who had pre- and post-intervention high-sensitivity troponin (hs-TnT) levels available. The delta (peak post-procedure minus baseline) troponin was compared between treatment arms. The association between delta troponin tertiles and three-year mortality was also evaluated. Three hundred and forty-three (343) patients were included, comprising patients treated with PCB (n=115), PES (n=112) and balloon angioplasty (n=116). Groups were well matched in terms of baseline characteristics. There was no difference in delta troponin in patients treated with PCB, PES and balloon angioplasty (36±65, 70±183, and 51±124 ng/L, respectively, p=0.16). Three-year mortality was 7.7%, 8.8% and 14.3% for the 1st, 2nd and 3rd tertiles of delta troponin, respectively, p=0.23. In patients with drug-eluting stent restenosis, there was no difference in subclinical myocardial necrosis among patients treated with PCB, PES, and balloon angioplasty.