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Stress Cardiac Biomarkers, Cardiovascular and Renal Outcomes, and Response to Canagliflozin.
Vaduganathan, M, Sattar, N, Xu, J, Butler, J, Mahaffey, KW, Neal, B, Shaw, W, Rosenthal, N, Pfeifer, M, Hansen, MK, et al
Journal of the American College of Cardiology. 2022;(5):432-444
Abstract
BACKGROUND Circulating biomarkers reflecting different mechanistic pathways may identify at-risk individuals with diabetes who may benefit from sodium-glucose cotransporter-2 (SGLT2) inhibitors. OBJECTIVES The purpose of this study was to determine if high-sensitivity cardiac troponin T (hs-cTnT), soluble suppression of tumorigenesis-2 (sST2), and insulin-like growth factor binding protein 7 (IGFBP7) levels, either alone or in combination, may modify the treatment benefits of canagliflozin. METHODS In the CANVAS (CANagliflozin cardioVascular Assessment Study) biomarker substudy, we evaluated the prognostic significance of baseline biomarker measurements, the long-term trajectory of each, and response to canagliflozin on key cardiovascular and kidney outcomes. RESULTS Among the 4,330 study participants, baseline hs-cTnT, sST2, and IGFBP7 were available in 3,503 (81%), 3,084 (71%), and 3,577 (83%). In total, 39% had elevated hs-cTnT ≥14 pg/mL, 6% had sST2 >35 ng/mL, and 49% had IGFBP7 >96.5 ng/mL. Canagliflozin significantly slowed increases of hs-cTnT (P = 0.027) and sST2 (P = 0.033) through 6 years. Each biomarker was significantly associated with cardiovascular and kidney outcomes, independent of clinical covariates. Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Patients with hs-cTnT ≥14 ng/L and those with sST2 >35 ng/mL derived greater relative benefit for major adverse cardiovascular events (MACE) (both Pinteraction ≤0.05). A panel of all 3 biomarkers predicted each cardiac and kidney outcome evaluated; participants with an increasing number of abnormal circulating biomarkers appeared to have greater relative reductions in MACE from canagliflozin treatment (Pinteraction trend = 0.005). CONCLUSIONS Canagliflozin delays longitudinal rise in hs-cTnT and sST2 compared with placebo out to 6 years. Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Elevated cardiovascular biomarkers, either alone or in combination, may identify individuals who may derive greater MACE benefit from SGLT2 inhibition. CANVAS (CANagliflozin cardioVascular Assessment Study; NCT01032629).
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Change in cardiac troponin T level after intravitreal anti-vascular endothelial growth factor treatment: Prospective pilot study.
Rebeiz, AG, Mahfoud, Z, Abdul Fattah, M, Saad, A, Safar, A, Bashshur, ZF
European journal of ophthalmology. 2020;(3):563-569
Abstract
BACKGROUND Evaluate subclinical myocardial injury associated with intravitreal anti-vascular endothelial growth factor therapy by measuring serum high-sensitivity cardiac troponin T. METHODS This is a prospective pilot comparative study conducted at American University of Beirut Medical Center, Beirut, Lebanon. In total, 40 consecutive patients were randomized to receive either intravitreal bevacizumab or ranibizumab. Patients received three consecutive monthly injections of the assigned drug, then continued treatment as needed. Systemic concentrations of high-sensitivity cardiac troponin T and vascular endothelial growth factor were obtained at baseline, week 9, and week 24. Primary endpoint measure was change in high-sensitivity cardiac troponin T levels compared to baseline. Secondary endpoint measure was change in systemic vascular endothelial growth factor levels. RESULTS There was no significant difference in high-sensitivity cardiac troponin T levels over time (p = 0.227) within each treatment group and no significant difference between treatments at any time point (p = 0.276). There was a significant decrease in plasma vascular endothelial growth factor levels at week 9 (p = 0.001) and week 24 (p < 0.001) compared to baseline. In the ranibizumab group, vascular endothelial growth factor levels were not significantly different at weeks 9 and 24 compared to baseline (p = 0.708 and p = 0.117, respectively). There was a significant association between the number of bevacizumab injections from weeks 8 to 24 and the decrease in vascular endothelial growth factor levels at week 24 (R = -0.67, p = 0.032). This correlation was not observed in the ranibizumab group (R = -0.341, p = 0.141). CONCLUSION Repeated intravitreal bevacizumab or ranibizumab did not influence serum high-sensitivity cardiac troponin levels. Intravitreal bevacizumab but not ranibizumab lowered free-systemic vascular endothelial growth factor levels, which was observed in this study to be inversely related to the number of bevacizumab injections.
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The impact of high-intensity interval training on the cTnT response to acute exercise in sedentary obese young women.
Nie, J, Zhang, H, He, Y, Cao, W, Liu, Y, Kong, Z, George, K
Scandinavian journal of medicine & science in sports. 2019;(2):160-170
Abstract
AIMS: This study characterized (a) the cardiac troponin T (cTnT) response to three forms of acute high-intensity interval exercise (HIE), and (b) the impact of 12 weeks of HIE training on the cTnT response to acute exercise in sedentary obese young women. METHODS Thirty-six sedentary women were randomized to traditional HIE training (repeated 4-minute cycling at 90% V˙ O2max interspersed with 3-minute rest, 200 kJ/session), work-equivalent sprint interval exercise (SIE) training (repeated 1-minute cycling at 120% V˙ O2max interspersed with 1.5-minute rest) or repeated-sprint exercise (RSE) training (40 × 6-second all-out sprints interspersed with 9-second rest) group. cTnT was assessed using a high-sensitivity assay before and immediately, 3 and 4 hours after the 1st (PRE), 6th (EARLY), 20th (MID), and 44th (END) training session, respectively. RESULTS cTnT was elevated (P < 0.05) after all forms of acute interval exercise at the PRE and EARLY assessment with cTnT response higher (P < 0.05) after HIE (307%) and SIE (318%) than RSE (142%) at the PRE assessment. All forms of acute interval exercise at MID and END had no effect on the cohort cTnT concentration post-exercise (all P > 0.05). CONCLUSION For sedentary obese young women, both HIE and SIE, matched for total work, induced a similar elevation in cTnT after acute exercise with a smaller rise observed after RSE. By the 44th training session, almost no post-exercise cTnT elevation was observed in all three groups. Such information is relevant for clinicians as it could improve medical decisionmaking.
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Predictive Value of High-Sensitivity Troponin T for Systolic Dysfunction and Infarct Size (Six Months) After ST-Elevation Myocardial Infarction.
Mohammad, MA, Koul, S, Smith, JG, Noc, M, Lang, I, Holzer, M, Clemmensen, P, Jensen, U, Engstrøm, T, Arheden, H, et al
The American journal of cardiology. 2018;(5):735-743
Abstract
The association of markers of myocardial injury and dysfunction with infarct size (IS) and ejection fraction (EF) are well documented. However, limited data are available on the newer high-sensitivity troponin assays and comparison with morphologic and functional assessment with cardiac magnetic resonance imaging. We aimed to examine the associations of high-sensitivity cardiac Troponin-T (hs-cTnT), creatine kinase MB iso-enzyme (CKMB), and N-terminal pro B-type Natriuretic Peptide (NT-proBNP) to IS and EF at 6 months. Blood samples from 119 ST-segment elevation myocardial infarction patients from the Rapid Endovascular Catheter Core Cooling Combined With Cold Saline solution as an Adjunct to Percutaneous Coronary Intervention for the Treatment of Acute Myocardial Infarction trial were collected at baseline, 6, 24, and 48 hours after admission. Cardiac magnetic resonance was performed at 4 ± 2 days and 6 months. The association of biomarker levels to IS and EF was tested with Pearson's correlation coefficients and linear regression models with bootstrap resampling. The correlation coefficient of biomarker to IS was (CKMB: r = 0.71); (NT-proBNP: r = 0.55); (hs-cTnT: r = 0.80); and for EF (CKMB: r = 0.57); (NT-proBNP: r = 0.48); and (peak hs-cTnT: r = 0.68). IS and EF at 4 ± 2 days had the strongest correlations with IS and EF at 6 months respectively (IS: r = 0.84) and (EF: r = 0.74). Receiver operating characteristic of peak hs-cTnT for predicting EF ≤40% at 6 months was 0.87 compared with 0.75 for early IS. Early EF was a negative predictor of late EF <40%, 1-area under curve = 0.93. In conclusion, high-sensitivity Troponin T is a rapid, cheap, generally available tool for accurate prediction of systolic dysfunction in patients 6 months after first-time ST-segment elevation myocardial infarction.
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Impact of high-intensity interval training and moderate-intensity continuous training on resting and postexercise cardiac troponin T concentration.
Nie, J, Zhang, H, Kong, Z, George, K, Little, JP, Tong, TK, Li, F, Shi, Q
Experimental physiology. 2018;(3):370-380
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NEW FINDINGS What is the central question of this study? Does exercise training impact resting and postexercise cardiac troponin T (cTnT) concentration? What is the main finding and its importance? This randomized controlled intervention study demonstrated that 12 weeks of either high-intensity interval training or moderate-intensity continuous training largely abolished the exercise-induced elevation in cTnT when exercise was performed at the same absolute intensity. There was no impact of training on resting cTnT or postexercise appearance of cTnT when exercise was performed at the same relative intensity. These findings provide new information that might help clinicians with decision-making in relationship to basal and postexercise values of cTnT in individuals with different training status. ABSTRACT We evaluated the influence of 12 weeks of high-intensity interval training [HIIT; repeated 4 min cycling at 90% of maximal oxygen uptake (V̇O2max) interspersed with 3 min rest, 200-300 kJ per session, 3 or 4 days each week] and work-equivalent moderate-intensity continuous training (MICT; continuous cycling at 60% V̇O2max) on resting cardiac troponin T (cTnT) and the appearance of exercise-induced cTnT. Forty-eight sedentary obese young women were randomly assigned to HIIT, MICT or a control group. The V̇O2max and body composition were measured before and after training. At baseline, cTnT was assessed using a high-sensitivity assay at rest and immediately, 2 and 4 h after 45 min cycling at 60% V̇O2max. After a 12 week training period, cTnT was assessed before and after 45 min cycling at the same relative and absolute intensities as before training. Training led to higher V̇O2max and lower fat mass in both HIIT and MICT groups (all P < 0.05). Before training, cTnT was significantly elevated in all three groups (by 35-118%, all P < 0.05) with acute exercise. After training, both resting and postexercise cTnT concentrations (same relative intensity) were similar to pretraining values. In contrast, postexercise cTnT (same absolute intensity, which represented a smaller exercise stimulus) was not elevated from rest in both HIIT and MICT groups. In conclusion, 12 weeks of either HIIT or MICT largely abolished the postexercise elevation of cTnT concentration when exercise was performed at the same absolute intensity. There was, however, no impact of training on resting cTnT or postexercise appearance of cTnT for exercise performed at the same relative intensity.
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High-Sensitivity Cardiac Troponin T Improves the Diagnosis of Perioperative MI.
Brown, JC, Samaha, E, Rao, S, Helwani, MA, Duma, A, Brown, F, Gage, BF, Miller, JP, Jaffe, AS, Apple, FS, et al
Anesthesia and analgesia. 2017;(5):1455-1462
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BACKGROUND The diagnosis of myocardial infarction (MI) after noncardiac surgery has traditionally relied on using relatively insensitive contemporary cardiac troponin (cTn) assays. We hypothesized that using a recently introduced novel high-sensitivity cTnT (hscTnT) assay would increase the detection rate of perioperative MI. METHODS In this ancillary study of the Vitamins in Nitrous Oxide trial, readjudicated incidence rates of myocardial injury (new isolated cTn elevation) and MI were compared when diagnosed by contemporary cTnI versus hscTnT. We probed various relative (eg, >50%) or absolute (eg, +5 ng/L) hscTnT change metrics. Inclusion criteria for this ancillary study were the presence of a baseline and at least 1 postoperative hscTnT value. RESULTS Among 605 patients, 70 patients (12%) had electrocardiogram changes consistent with myocardial ischemia; 82 patients (14%) had myocardial injury diagnosed by contemporary cTnI, 31 (5.1%) of which had an adjudicated MI. After readjudication, 67 patients (11%) were diagnosed with MI when using hscTnT, a 2-fold increase. Incidence rates of postoperative myocardial injury ranged from 12% (n = 73) to 65% (n = 393) depending on the hscTnT metric used. Incidence rates of MI using various hscTnT change metrics and the presence of ischemic electrocardiogram changes, but without event adjudication, ranged from 3.6% (n = 22) to 12% (n = 74), a >3-fold difference. New postoperative hscTnT elevation, either by absolute or relative hscTnT change metric, was associated with an up to 5-fold increase in 6-month mortality. CONCLUSIONS The use of hscTnT compared to contemporary cTnI increases the detection rate of perioperative MI by a factor of 2. Using different absolute or relative hscTnT change metrics may lead to under- or overdiagnosis of perioperative MI.
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Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP.
Kopec, M, Duma, A, Helwani, MA, Brown, J, Brown, F, Gage, BF, Gibson, DW, Miller, JP, Novak, E, Jaffe, AS, et al
Anesthesia and analgesia. 2017;(2):398-405
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BACKGROUND This study sought to determine whether preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major noncardiac surgery compared with the standard risk indices. METHODS In this ancillary study to the Vitamins in Nitrous Oxide trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n = 572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first 3 postoperative days. hs-cTnT was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated on the basis of receiver operating characteristic statistics. Biomarker risk prediction was compared with Lee's Revised Cardiac Risk Index (RCRI) with the use of standard methods and net reclassification index. RESULTS The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 [5.2%], Area under the receiver operating characteristic curve increased from 0.590 to 0.716 with a 0.66 net reclassification index [95% confidence interval 0.32-0.99], P < .001). The use of 108 ng/L as a cutoff for NT-proBNP improved sensitivity compared with 300 ng/L (0.87 vs 0.53). Sensitivity, specificity, positive, and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09, and 0.97 and for NT-proBNP were 0.53, 0.68, 0.08, and 0.96. CONCLUSIONS The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves the prediction of adverse cardiac events in the immediate postoperative period after major noncardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a "rule-out" test to confirm low risk of postoperative MI.
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Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.
Lindholm, D, Lindbäck, J, Armstrong, PW, Budaj, A, Cannon, CP, Granger, CB, Hagström, E, Held, C, Koenig, W, Östlund, O, et al
Journal of the American College of Cardiology. 2017;(7):813-826
Abstract
BACKGROUND Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). OBJECTIVES This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. METHODS In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. RESULTS During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This "ABC-CHD" model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. CONCLUSIONS This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903).
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Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy.
Bidadkosh, A, Lambooy, SPH, Heerspink, HJ, Pena, MJ, Henning, RH, Buikema, H, Deelman, LE
Diabetes care. 2017;(6):784-792
Abstract
OBJECTIVE Although patients with type 2 diabetes (T2D) with nephropathy are at high risk for renal and cardiovascular complications, relevant biomarkers have been poorly identified. Because renal impairment may increase biomarker levels, this potentially confounds associations between biomarker levels and risk. To investigate the predictive value of a biomarker in such a setting, we examined baseline levels of growth differentiation factor-15 (GDF-15), N-terminal prohormone of B-type natriuretic peptide (NTproBNP), and high-sensitivity troponin T (hs-TnT) in relation to renal and cardiovascular risk in T2D patients with nephropathy. RESEARCH DESIGN AND METHODS Eight hundred sixty-one T2D patients from the sulodexide macroalbuminuria (Sun-MACRO) trial were included in our post hoc analysis. Prospective associations of baseline serum GDF-15, NTproBNP, and hs-TnT with renal and cardiovascular events were determined by Cox multiple regression and C-statistic analysis. Renal base models included albumin-to-creatinine ratio (ACR), serum creatinine, hemoglobin, age, and sex. Cardiovascular base models included diastolic blood pressure, ACR, cholesterol, age, and sex. RESULTS The mean (±SD) estimated glomerular filtration rate was 33 ± 9 mL/min/1.73 m2, and the median serum concentration for GDF-15 was 3,228 pg/mL (interquartile range 2,345-4,310 pg/mL), for NTproBNP was 380 ng/L (155-989 ng/L), and for hs-TnT was 30 ng/L (20-47 ng/L). In multiple regression analysis, GDF-15 (hazard ratio [HR] 1.83, P = 0.04), NTproBNP (HR 2.34, P = 0.004), and hs-TnT (HR 2.09, P = 0.014) were associated with renal events, whereas NTproBNP (HR 3.45, P < 0.001) was associated with cardiovascular events. The C-statistic was improved by adding NTproBNP and hs-TNT to the renal model (0.793 vs. 0.741, P = 0.04). For cardiovascular events, the C-statistic was improved by adding NTproBNP alone (0.722 vs. 0.658, P = 0.018). CONCLUSIONS Biomarkers GDF-15, NTproBNP, and hs-TnT associate independently with renal risk, whereas NTproBNP independently predicts cardiovascular risk.
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Cardiac troponin T and echocardiographic dimensions after repeated sprint vs. moderate intensity continuous exercise in healthy young males.
Weippert, M, Divchev, D, Schmidt, P, Gettel, H, Neugebauer, A, Behrens, K, Wolfarth, B, Braumann, KM, Nienaber, CA
Scientific reports. 2016;:24614
Abstract
Regular physical exercise can positively influence cardiac function; however, investigations have shown an increase of myocardial damage biomarkers after acute prolonged endurance exercises. We investigated the effect of repeated sprint vs. moderate long duration exercise on markers of myocardial necrosis, as well as cardiac dimensions and functions. Thirteen healthy males performed two different running sessions (randomized, single blinded cross-over design): 60 minutes moderate intensity continuous training (MCT, at 70% of peak heart rate (HRpeak)) and two series of 12 × 30-second sprints with set recovery periods in-between (RST, at 90% HRpeak). Venous blood samples for cardiac troponin T (cTnT), creatine kinase (CK) and MB isoenzyme (CK-MB) were taken 1 and 4 hours after exercise sessions. After each session electrocardiographic (ECG) and transthoracic echocardiographic (TTE) data were recorded. Results showed that all variables - average heart rate, serum lactate concentration during RST, subjective exertion and cTnT after RST - were significantly higher compared to MCT. CK and CK-MB significantly increased regardless of exercise protocol, while ECG and TTE indicated normal cardiac function. Our results provide evidence that RST contributes significantly to cTnT and CK release. This biomarker increase seems to reflect a physiological rather than a pathological phenomenon in healthy, exercising subjects.