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Safety and efficacy study of prourokinase injection during primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction.
Jiang, W, Xiong, X, Du, X, Ma, H, Li, W, Cheng, F
Coronary artery disease. 2021;(1):25-30
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Abstract
OBJECTIVES To evaluate the efficacy and safety of intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions in patients with acute ST-segment elevation myocardial infarction. METHODS Acute ST-segment elevation myocardial infarction patients underwent primary percutaneous coronary interventions were randomly divided into two groups: intracoronary prourokinase group (n = 125) and control group (n = 135). During primary percutaneous coronary interventions, prourokinase or saline was injected to the distal end of the culprit lesion via balloon catheter after balloon catheter dilatation. Demographic and clinical characteristics, infarct size, myocardial reperfusion, and cardiac functions were evaluated and compared between two groups. Hemorrhagic complications and major averse cardiovascular events (MACE) occurred in the 6-months follow-up were recorded. RESULTS No significant differences were observed between two groups with respect to baseline demographic, clinical, and thrombolysis in myocardial infarction grade (P > 0.05). In the intracoronary prourokinase group, more patients had ST-segment resolution (>50%) compared with control group (P < 0.05). Patients in the intracoronary prourokinase group showed lower levels of serum CK, creatine kinase-MB fraction, and troponin I than those in control group (P < 0.05). No significant differences in bleeding complications were observed between the two groups (P > 0.05). At 6-months follow-up, there was no statistically different of MACE between the two groups (P > 0.05). CONCLUSIONS Intracoronary administration of prourokinase via balloon catheter during primary percutaneous coronary interventions effectively improved myocardial perfusion and no increased bleeding in ST-segment elevation myocardial infarction patients.
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Effects of Diet and Sodium Reduction on Cardiac Injury, Strain, and Inflammation: The DASH-Sodium Trial.
Juraschek, SP, Kovell, LC, Appel, LJ, Miller, ER, Sacks, FM, Chang, AR, Christenson, RH, Rebuck, H, Mukamal, KJ
Journal of the American College of Cardiology. 2021;(21):2625-2634
Abstract
BACKGROUND The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown. OBJECTIVES The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation. METHODS DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period. RESULTS Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: -27% to -7%) and hs-CRP by 13% (95% CI: -24% to -1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: -24% to -14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: -31% to -7%) and NT-proBNP by 23% (95% CI: -32% to -12%), whereas hs-CRP was not significantly changed (-7%; 95% CI: -22% to 9%) compared with the high sodium-control diet. CONCLUSIONS Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH - Sodium]; NCT00000608).
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A Rapid (Differential) Effect of Rosuvastatin and Atorvastatin on High-Sensitivity Cardiac Troponin-I in Subjects With Stable Cardiovascular Disease.
Bodde, MC, Welsh, P, Bergheanu, SC, Lijfering, WM, Mertens, B, Liem, AH, van der Laarse, A, Sattar, N, Jukema, JW
Clinical pharmacology and therapeutics. 2018;(2):311-316
Abstract
Serum troponin within the normal range is an emerging predictor of cardiovascular mortality. We aimed to determine how rapidly high-sensitivity troponin-I (hs-cTnI) levels are lowered by statin therapy in patients with stable cardiovascular disease. In the RADAR substudy, patients were randomized to atorvastatin 20 mg/day (n = 39) or rosuvastatin 10 mg/day (n = 39) and up-titrated at 6-week intervals to 80 mg of atorvastatin or 40 mg of rosuvastatin. Hs-cTnI concentrations were measured at baseline and at 6 and 18 weeks of follow-up. Statin treatment resulted in a mean change of serum hs-cTnI of -8.2% (P = 0.010) after 6 weeks and -12.3% (P = 0.001) after 18 weeks. After 18 weeks, hs-cTnI levels were lowered by 21.8% with atorvastatin and by 4.1% with rosuvastatin (P = 0.001 and P = 0.133, respectively). During statin therapy, serum hs-cTnI levels decreased rapidly within weeks of treatment, suggesting an effect beyond long-term atherosclerosis regression. Mechanisms that mediate this effect require further study.
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Myocardial inflammation, injury and infarction during on-pump coronary artery bypass graft surgery.
Alam, SR, Stirrat, C, Spath, N, Zamvar, V, Pessotto, R, Dweck, MR, Moore, C, Semple, S, El-Medany, A, Manoharan, D, et al
Journal of cardiothoracic surgery. 2017;(1):115
Abstract
BACKGROUND Myocardial inflammation and injury occur during coronary artery bypass graft (CABG) surgery. We aimed to characterise these processes during routine CABG surgery to inform the diagnosis of type 5 myocardial infarction. METHODS We assessed 87 patients with stable coronary artery disease who underwent elective CABG surgery. Myocardial inflammation, injury and infarction were assessed using plasma inflammatory biomarkers, high-sensitivity cardiac troponin I (hs-cTnI) and cardiac magnetic resonance imaging (CMR) using both late gadolinium enhancement (LGE) and ultrasmall superparamagnetic particles of iron oxide (USPIO). RESULTS Systemic humoral inflammatory biomarkers (myeloperoxidase, interleukin-6, interleukin-8 and c-reactive protein) increased in the post-operative period with C-reactive protein concentrations plateauing by 48 h (median area under the curve (AUC) 7530 [interquartile range (IQR) 6088 to 9027] mg/L/48 h). USPIO-defined cellular myocardial inflammation ranged from normal to those associated with type 1 myocardial infarction (median 80.2 [IQR 67.4 to 104.8] /s). Plasma hs-cTnI concentrations rose by ≥50-fold from baseline and exceeded 10-fold the upper limit of normal in all patients. Two distinct patterns of peak cTnI release were observed at 6 and 24 h. After CABG surgery, new LGE was seen in 20% (n = 18) of patients although clinical peri-operative type 5 myocardial infarction was diagnosed in only 9% (n = 8). LGE was associated with the delayed 24-h peak in hs-cTnI and its magnitude correlated with AUC plasma hs-cTnI concentrations (r = 0.33, p < 0.01) but not systemic inflammation, myocardial inflammation or bypass time. CONCLUSION Patients undergoing CABG surgery invariably have plasma hs-cTnI concentrations >10-fold the 99th centile upper limit of normal that is not attributable to inflammatory or ischemic injury alone. Peri-operative type 5 myocardial infarction is often unrecognised and is associated with a delayed 24-h peak in plasma hs-cTnI concentrations.
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Effects of Canagliflozin on Cardiovascular Biomarkers in Older Adults With Type 2 Diabetes.
Januzzi, JL, Butler, J, Jarolim, P, Sattar, N, Vijapurkar, U, Desai, M, Davies, MJ
Journal of the American College of Cardiology. 2017;(6):704-712
Abstract
BACKGROUND Sodium glucose co-transporter 2 inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM). OBJECTIVES The goal of this study was to examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM. METHODS In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, the study assessed the median percent change in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI), soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks. RESULTS Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients, but they remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were -15.0%, -16.1%, and -26.8% for NT-proBNP, and -8.3%, -11.9%, and -10.0% for hsTnI at weeks 26, 52, and 104, respectively (all p < 0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed. CONCLUSIONS Compared with placebo, treatment with canagliflozin delayed the rise in serum NT-proBNP and hsTnI for over 2 years in older T2DM patients. These cardiac biomarker data provide support for the beneficial cardiovascular effect of sodium glucose co-transporter 2 inhibitors in T2DM. (A Safety and Efficacy Study of Canagliflozin in Older Patients [55 to 80 Years of Age] With Type 2 Diabetes Mellitus; NCT01106651).
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Troponin I levels in permanent atrial fibrillation-impact of rate control and exercise testing.
Horjen, AW, Ulimoen, SR, Enger, S, Norseth, J, Seljeflot, I, Arnesen, H, Tveit, A
BMC cardiovascular disorders. 2016;:79
Abstract
BACKGROUND High-sensitivity troponin I (hs-TnI) and troponin T (hs-TnT) are moderately correlated and independently related to outcome in atrial fibrillation (AF). Rate controlling therapy has been shown to reduce hs-TnT, however the potential impact on hs-TnI levels, and whether this differs from the effects on hs-TnT, has not been investigated previously. METHODS Sixty patients with stable, permanent AF without heart failure or known ischemic heart disease were included in a randomised crossover study (mean age 71 ± 9 years, 18 women). Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered once daily for three weeks, in a randomised sequence. At baseline and on the last day of each treatment period, hs-TnI was measured at rest and after a maximal exercise test and compared to hs-TnT. RESULTS Hs-TnI and hs-TnT correlated moderately at baseline (rs = 0.582, p < 0.001). All drugs reduced both the resting and the peak exercise levels of hs-TnI compared with baseline (p < 0.001 for all). The decline in resting hs-TnI and hs-TnT values relative to baseline levels was similar for all drugs except for verapamil, which reduced hs-TnI more than hs-TnT (p = 0.017). Levels of hs-TnI increased significantly in response to exercise testing at baseline and at all treatment regimens (p < 0.001 for all). The relative exercise-induced increase in hs-TnI was significantly larger compared to hs-TnT at baseline (p < 0.001), on diltiazem (p < 0.001) and on verapamil (p = 0.001). CONCLUSIONS In our population of stable, permanent AF patients, all four rate control drug regimens reduced hs-TnI significantly, both at rest and during exercise. The decline in hs-TnI and hs-TnT levels associated with beta-blocker and calcium channel blocker treatment was similar, except for a larger relative decrease in hs-TnI levels following verapamil treatment. TRIAL REGISTRATION www.clinicaltrials.gov ( NCT00313157 ).
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Cardiac Troponin T and I Release After a 30-km Run.
Klinkenberg, LJ, Luyten, P, van der Linden, N, Urgel, K, Snijders, DP, Knackstedt, C, Dennert, R, Kietselaer, BL, Mingels, AM, Cardinaels, EP, et al
The American journal of cardiology. 2016;(2):281-7
Abstract
Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4 × 5 min 220 mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs-cTnT, hs-cTnI, and s-cTnI levels of 47 ± 27, 69 ± 62, and 82 ± 64 ng/L (mean ± SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time × trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction.
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High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease.
Ford, I, Shah, AS, Zhang, R, McAllister, DA, Strachan, FE, Caslake, M, Newby, DE, Packard, CJ, Mills, NL
Journal of the American College of Cardiology. 2016;(25):2719-2728
Abstract
BACKGROUND Cardiac troponin is an independent predictor of cardiovascular mortality in individuals without symptoms or signs of cardiovascular disease. The mechanisms for this association are uncertain, and a role for troponin testing in the prevention of coronary heart disease has yet to be established. OBJECTIVES This study sought to determine whether troponin concentration could predict coronary events, be modified by statins, and reflect response to therapy in a primary prevention population. METHODS WOSCOPS (West of Scotland Coronary Prevention Study) randomized men with raised low-density lipoprotein cholesterol and no history of myocardial infarction to pravastatin 40 mg once daily or placebo for 5 years. Plasma cardiac troponin I concentration was measured with a high-sensitivity assay at baseline and at 1 year in 3,318 participants. RESULTS Baseline troponin was an independent predictor of myocardial infarction or death from coronary heart disease (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.4 to 3.7) for the highest (≥5.2 ng/l) versus lowest (≤3.1 ng/l) quarter of troponin (p < 0.001). There was a 5-fold greater reduction in coronary events when troponin concentrations decreased by more than a quarter, rather than increased by more than a quarter, for both placebo (HR: 0.29; 95% CI: 0.12 to 0.72 vs. HR: 1.95; 95% CI: 1.09 to 3.49; p < 0.001 for trend) and pravastatin (HR: 0.23; 95% CI: 0.10 to 0.53 vs. HR: 1.08; 95% CI: 0.53 to 2.21; p < 0.001 for trend). Pravastatin reduced troponin concentration by 13% (10% to 15%; placebo adjusted, p < 0.001) and doubled the number of men whose troponin fell more than a quarter (p < 0.001), which identified them as having the lowest risk for future coronary events (1.4% over 5 years). CONCLUSIONS Troponin concentration predicts coronary events, is reduced by statin therapy, and change at 1 year is associated with future coronary risk independent of cholesterol lowering. Serial troponin measurements have major potential to assess cardiovascular risk and monitor the impact of therapeutic interventions.
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Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial).
Daaboul, Y, Korjian, S, Weaver, WD, Kloner, RA, Giugliano, RP, Carr, J, Neal, BJ, Chi, G, Cochet, M, Goodell, L, et al
The American journal of cardiology. 2016;(5):625-31
Abstract
Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size.
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hs-Troponin I Followed by CT Angiography Improves Acute Coronary Syndrome Risk Stratification Accuracy and Work-Up in Acute Chest Pain Patients: Results From ROMICAT II Trial.
Ferencik, M, Liu, T, Mayrhofer, T, Puchner, SB, Lu, MT, Maurovich-Horvat, P, Pope, JH, Truong, QA, Udelson, JE, Peacock, WF, et al
JACC. Cardiovascular imaging. 2015;(11):1272-1281
Abstract
OBJECTIVES This study compared diagnostic accuracy of conventional troponin/traditional coronary artery disease (CAD) assessment and highly sensitive troponin (hsTn) I/advanced CAD assessment for acute coronary syndrome (ACS) during the index hospitalization. BACKGROUND hsTnI and advanced assessment of CAD using coronary computed tomography angiography (CTA) are promising candidates to improve the accuracy of emergency department evaluation of patients with suspected ACS. METHODS We performed an observational cohort study in patients with suspected ACS enrolled in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia using Computer Assisted Tomography) trial and randomized to coronary CTA who also had hsTnI measurement at the time of the emergency department presentation. We assessed coronary CTA for traditional (no CAD, nonobstructive CAD, ≥50% stenosis) and advanced features of CAD (≥50% stenosis, high-risk plaque features: positive remodeling, low <30-Hounsfield units plaque, napkin-ring sign, spotty calcium). RESULTS Of 160 patients (mean age: 53 ± 8 years, 40% women) 10.6% were diagnosed with ACS. The ACS rate in patients with hsTnI below the limit of detection (n = 9, 5.6%), intermediate (n = 139, 86.9%), and above the 99th percentile (n = 12, 7.5%) was 0%, 8.6%, and 58.3%, respectively. Absence of ≥50% stenosis and high-risk plaque ruled out ACS in patients with intermediate hsTnI (n = 87, 54.4%; ACS rate 0%), whereas patients with both ≥50% stenosis and high-risk plaque were at high risk (n = 13, 8.1%; ACS rate 69.2%) and patients with either ≥50% stenosis or high-risk plaque were at intermediate risk for ACS (n = 39, 24.4%; ACS rate 7.7%). hsTnI/advanced coronary CTA assessment significantly improved the diagnostic accuracy for ACS as compared to conventional troponin/traditional coronary CTA (area under the curve 0.84, 95% confidence interval [CI]: 0.80 to .88 vs. 0.74, 95% CI: 0.70 to 0.78; p < 0.001). CONCLUSIONS hsTnI at the time of presentation followed by early advanced coronary CTA assessment improves the risk stratification and diagnostic accuracy for ACS as compared to conventional troponin and traditional coronary CTA assessment. (Multicenter Study to Rule Out Myocardial Infarction/Ischemia by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).