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Objective: To examine changes in concentration, time-to-peak and the ensuing half-life of cardiac biomarkers in patients with myocardial infarction. Methods: Blood sampling was performed every third hour within 24 h after percutaneous coronary intervention (PCI) on a cohort of patients with ST elevation myocardial infarction. Cardiac troponin (cTn) was measured by the Dimension Vista, Vitros, Atellica, and Alinity high-sensitivity (hs) cTnI assays, and the Elecsys hs-cTnT assay. Further, creatine kinase (CK), myoglobin, creatine kinase MB (CKMB) and other biomarkers were analyzed. Results: A total of 36 patients completed blood sampling (median age 60 years, IQR 56.4–66.5 years; seven women, 19.4%). Hs-cTnI measured by the Vitros assay was the first hs-cTn to peak at 9.1 h (95%-CI 6.2–10.1) after PCI and 11.7 h (95%-CI 10.4–14.8) after symptoms onset. There were no notable differences between hs-cTn assays in regard to time-to-peak. Also, Vitros hs-cTnI reached the highest median ratio of concentration to upper reference level of nearly 2,000. The median half-life from peak concentration ranged from 7.6 h for myoglobin (CI 6.8–8.6) to 17.8 h for CK (CI 6.8–8.6). For hs-cTn assays the median T½ ranged from 12.4 h for the Vista hs-cTnI assay (95%-CI 11.0–14.1 h) to 17.3 h for the Elecsys hs-cTnT (95%-CI 14.9–20.8 h). Conclusions: This study updates knowledge on the kinetics of cardiac biomarkers in current clinical use. There was no notable difference in trajectories, time-to-peak or half-life between hs-cTn assays.

ObjectivesThe analytical sensitivity of high-sensitivity cardiac troponin T (hsTnT) assays has enabled rapid myocardial infarction rule-out algorithms for emergency department (ED) presentations. Few studies have analyzed the real-world impact of hsTnT algorithms on outcomes and operations.MethodsComparison of ED length of stay (LOS) and 30-day outcomes (return to ED, inpatient admission, and mortality) for patients presenting with chest pain during 2 separate 208-day periods using a 0/1-hour hsTnT-enabled algorithm or fourth-generation TnT.ResultsDischarge, 30-day readmission, and 30-day mortality rates were not significantly different with fourth-generation TnT vs hsTnT. Thirty-day return rates were significantly decreased with hsTnT (17.4% vs 14.9%; P < .01). For encounters with TnT measured at least twice and resulting in discharge, median ED LOS decreased by 61 minutes with the use of hsTnT (488 vs 427 minutes; P < .0001). Median time between first and second TnT results decreased by 82 minutes with hsTnT (202 vs 120 minutes; P < .0001), suggesting that the 0/1-hour algorithm was incompletely adopted.ConclusionsImplementation of the hsTnT algorithm was associated with decreased 30-day return rates and decreased ED LOS for a subset of patients, despite incomplete adoption of the 0/1-hour algorithm.

We demonstrate that a novel functionalized interface, where molecularly imprinted polymer nanoparticles (nanoMIPs) are attached to screen-printed graphite electrodes (SPEs), can be utilized for the thermal detection of the cardiac biomarker troponin I (cTnI). The ultrasensitive detection of the unique protein cTnI can be utilized for the early diagnosis of myocardial infraction (i.e. heart attacks), resulting in considerably lower patient mortality and morbidity. Our developed platform presents an innovative route to develop accurate, low-cost, and disposable sensors for the diagnosis of cardiovascular diseases, specifically myocardial infraction. A reproducible and advantageous solid-phase approach was utilized to synthesize high-affinity nanoMIPs (average size = 71 nm) for cTnI, which served as synthetic receptors in a thermal sensing platform. To assess the performance and commercial potential of the sensor platform, various approaches were used to immobilize nanoMIPs onto thermocouples or SPEs: dip coating, drop casting, and a covalent approach relying on electrografting with an organic coupling reaction. Characterization of the nanoMIP-functionalized surfaces was performed with electrochemical impedance spectroscopy, atomic force microscopy, and scanning electron microscopy. Measurements from an in-house designed thermal setup revealed that covalent functionalization of nanoMIPs onto SPEs led to the most reproducible sensing capabilities. The proof of application was provided by measuring buffered solutions spiked with cTnI, which demonstrated that through monitoring changes in heat transfer at the solid-liquid interface, we can measure concentrations as low as 10 pg L-1, resulting in the most sensitive test of this type. Furthermore, preliminary data are presented for a prototype platform, which can detect cTnI with shorter measurement times and smaller sample volumes. The excellent sensor performance, versatility of the nanoMIPs, and reproducible and low-cost, SCOPUS: ar.j, info:eu-repo/semantics/published

New drugs come not only with benefits but also with unexpected toxicities which need to be promptly recognized and managed. Starting from a scholar case of acute heart failure with preserved ejection fraction following the administration of trabectedin (ET-743, Yondelis®) in a patient with a metastatic solitary fibrous tumor, we performed a systematic review of the literature encompassing the results of previous cardiac safety analysis published ten years ago, a review of clinical trials published during the last 10 years as well as single-case descriptions related to trabectedin cardiotoxicity. The estimated incidence of cardiac toxicity was 3,4% among patients receiving trabectedin, with recent data suggesting a higher rate of heart failure than previously recognized. Previous or concomitant anthracyclines exposure may represent a risk factor. Assaying for NT-pro-BNP may be useful for the early detection of individuals with trabectedin-induced heart failure., SCOPUS: re.j, info:eu-repo/semantics/published

Background: It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood.Objectives: We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction.Methods: We included 2961 participants from the population-based Maastricht Study (mean +/- SD age 59.8 +/- 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors.Results: Median [QR] 24-h UNaE and UKE were 3.7 (2.8-4.71 g/24 h and 3.0 12.4-3.61 g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium.Conclusions: Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports r

Cardiovascular diseases represent, to date, the major cause of mortality worldwide. Diagnosis of the most frequent of such disease, acute myocardial infarction (AMI), requires the evaluation of time-series measurement of specific cardiac biomarkers concentration. The aim of this paper is to provide the clinicians with a quantitative tool to analyze such time-series, with the final goal of enhancing the diagnostic and prognostic procedures. The proposed approach is based on a novel dynamical model, which synthetically describes the basic mechanisms underlying cardiac troponin (cTnT) release into the plasma after the onset of AMI. Leveraging tools of system identification and a data set of AMI patients treated at our University Hospital, the model has been assessed as an effective tool to quantify the characteristic release curves observed under different conditions. Furthermore, it has been shown how the devised approach is also suitable in those cases where only partial measurements are available to the clinician to recover important clinical information. Finally, an optimal experimental design analysis has been performed in order to gain insights on how to optimize the experimental data collection phase with potentially relevant implications on both the quality and cost of the diagnosis procedure

Background: It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood.Objectives: We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction.Methods: We included 2961 participants from the population-based Maastricht Study (mean +/- SD age 59.8 +/- 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors.Results: Median [QR] 24-h UNaE and UKE were 3.7 (2.8-4.71 g/24 h and 3.0 12.4-3.61 g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium.Conclusions: Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports r

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

This manuscript describes the production of molecularly imprinted polymer nanoparticles (nanoMIPs) for the cardiac biomarkers heart-fatty acid binding protein (H-FABP) and ST2 by solid-phase synthesis, and their use as synthetic antibodies in a multiplexed sensing platform. Analysis by surface plasmon resonance (SPR) shows that the affinity of the nanoMIPs is similar to that of commercially available antibodies. The particles are coated onto the surface of thermocouples and inserted into 3D-printed flow cells of different multiplexed designs. We demonstrate that it is possible to selectively detect both cardiac biomarkers within the physiologically relevant range. Furthermore, the developed sensor platform is the first example of a multiplex format of this thermal analysis technique which enables simultaneous measurements of two different compounds with minimal cross selectivity. The format where three thermocouples are positioned in parallel exhibits the highest sensitivity, which is explained by modeling the heat flow distribution within the flow cell. This design is used in further experiments and proof-of-application of the sensor platform is provided by measuring spiked fetal bovine serum samples. Because of the high selectivity, short measurement time, and low cost of this array format, it provides an interesting alternative to traditional immunoassays. The use of nanoMIPs enables a multimarker strategy, which has the potential to contribute to sustainable healthcare by improving the reliability of cardiac biomarker testing.

This manuscript describes the production of molecularly imprinted polymer nanoparticles (nanoMIPs) for the cardiac biomarkers heart-fatty acid binding protein (H-FABP) and ST2 by solid-phase synthesis, and their use as synthetic antibodies in a multiplexed sensing platform. Analysis by surface plasmon resonance (SPR) shows that the affinity of the nanoMIPs is similar to that of commercially available antibodies. The particles are coated onto the surface of thermocouples and inserted into 3D-printed flow cells of different multiplexed designs. We demonstrate that it is possible to selectively detect both cardiac biomarkers within the physiologically relevant range. Furthermore, the developed sensor platform is the first example of a multiplex format of this thermal analysis technique which enables simultaneous measurements of two different compounds with minimal cross selectivity. The format where three thermocouples are positioned in parallel exhibits the highest sensitivity, which is explained by modeling the heat flow distribution within the flow cell. This design is used in further experiments and proof-of-application of the sensor platform is provided by measuring spiked fetal bovine serum samples. Because of the high selectivity, short measurement time, and low cost of this array format, it provides an interesting alternative to traditional immunoassays. The use of nanoMIPs enables a multimarker strategy, which has the potential to contribute to sustainable healthcare by improving the reliability of cardiac biomarker testing.

BackgroundRegression of left ventricular hypertrophy (LVH) is feasible with more frequent hemodialysis (HD). We aimed to ascertain pathways associated with regression of left ventricular mass (LVM) in patients enrolled in the Frequent HD Network (FHN) trials.MethodsThis was a post hoc observational cohort study. We hypothesized LVH regression with frequent HD was associated with a different cardiovascular biomarker profile. Regressors were defined as patients who achieved a reduction of more than 10% in LVM at 12 months. Progressors were defined as patients who had a minimum of 10% increase in LVM at 12 months.ResultsAmong 332 randomized patients, 243 had biomarker data available. Of these, 121 patients did not progress or regress, 77 were regressors, and 45 were progressors. Mean LVM change differed between regressors and progressors by -65.6 (-74.0 to -57.2) g, p < 0.001. Regressors had a median (interquartile range) increase in dialysis frequency (from 3.0 [3.0-3.0] to 4.9 [3-5.7] per week, p = 0.001) and reductions in pre-dialysis systolic (from 149.0 [136.0-162.0] to 136.0 [123.0-152.0] mm Hg, p < 0.001) and diastolic (from 83.0 [71.0-91.0] to 76.0 [68.0-84.0] mm Hg, p < 0.001) blood pressures. Klotho levels increased in regressors versus progressors (76.9 [10.5-143.3] pg/mL, p = 0.024). Tissue inhibitors of metalloproteinase (TIMP)-2 levels fell in regressors compared to progressors (-7,853 [-14,653 to -1,052] pg/mL, p = 0.024). TIMP-1 and log (brain natriuretic -peptide [BNP]) levels also tended to fall in regressors. Changes in LVM correlated inversely with changes in klotho (r = -0.24, p = 0.014). -Conclusions: Markers of collagen turnover and changes in klotho levels are potential novel pathways associated with regression of LVH in the dialysis population, which will require further prospective validation.

Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are molecular markers that may allow earlier detection of drug-induced cardiotoxicity. In this analysis we aimed to quantify the kinetics and exposure-response relationships of LVEF, troponin T and NT-proBNP measurements, in patients receiving anthracycline and trastuzumab. Repeated measurements of LVEF, troponin T and NT-proBNP and dosing records of anthracyclines and trastuzumab were available from a previously published clinical trial. This trial included 206 evaluable patients with early breast cancer. Exposure to anthracycline and trastuzumab was simulated based on available dosing records and by using a kinetic-pharmacodynamic (K-PD) and a fixed pharmacokinetic (PK) model from literature, respectively. The change from baseline troponin T was described with a direct effect model, affected by simulated anthracycline concentrations, representing myocyte damage. The relationship between trastuzumab and LVEF was described by an indirect effect compartment model. The EC50 for LVEF decline was significantly affected by the maximum troponin T concentration after anthracycline treatment, explaining 15.1% of inter-individual variability. In this cohort, NT-proBNP changes could not be demonstrated to be related to anthracycline or trastuzumab treatment. Pharmacodynamic models for troponin T and LVEF were successfully developed, identifying maximum troponin T concentration after anthracycline treatment as a significant determinant for trastuzumab-induced LVEF decline. These models can help identify patients at risk of drug-induced cardiotoxicity and optimize cardiac monitoring strategies.

BackgroundAn analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS.MethodsBlood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size.ResultsWe included 89 patients with OSA and 38 patients without OSA with an apnea-hypopnea index of a median of 32 (interquartile range [IQR], 20.8-46.6/h and 4.8 [IQR, 1.6-9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78-40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37-24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA.ConclusionsThe results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.

Background & aims: Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD.Methods: This double-blind, randomized cross-over placebo controlled trial included 20 mild-to moderate COPD patients (66.6 +/- 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 +/- 3 kg/m(2)) but high prevalence of abdominal obesity (833%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (similar to 8 mmoliday) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated.Results: Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure.Conclusion: Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate COPD patients. (C) 2017 Elsevier Ltd and European Society

Background & aims: Many COPD patients have a reduced exercise capacity and mechanical efficiency and are at increased cardiometabolic risk. This study aimed to assess acute and 7-days effects of dietary nitrate on mechanical efficiency, exercise performance and cardiac biomarkers in patients with COPD.Methods: This double-blind, randomized cross-over placebo controlled trial included 20 mild-to moderate COPD patients (66.6 +/- 7.5 years) with moderate exercise impairments and decreased mechanical efficiency, normal BMI (26 +/- 3 kg/m(2)) but high prevalence of abdominal obesity (833%). Subjects were randomly allocated to the treatment order of 7 days sodium nitrate ingestion (similar to 8 mmoliday) and 7 days placebo (NaCl solution) or vice versa, separated by a washout period. Before (Day-1) and after (Day-7) both intervention periods resting metabolic rate and the metabolic response during submaximal cycle ergometry, cycling endurance time, plasma nitrate and nitrite levels, cardiac plasma biomarkers (e.g. cardiac troponin T, Nt-proBNP and creatinine kinase) and blood pressure were measured. Subsequently, gross, net and delta mechanical efficiency were calculated.Results: Plasma nitrate and nitrite concentrations increased at Day-1 and Day-7 after sodium nitrate but not after placebo ingestion. Systolic and diastolic blood pressure did not change following nitrate ingestion. Furthermore, no differences were observed in gross, net, and delta mechanical efficiency during submaximal exercise, cycling endurance time and cardiac biomarkers between nitrate and placebo on Day-1 and Day-7. Meta-analysis of all available studies in COPD also showed no beneficial effect of beetroot juice on systolic and diastolic blood pressure.Conclusion: Acute as well as 7-days sodium nitrate supplementation does not modulate mechanical efficiency, blood pressure or cardiac biomarkers in mild-to-moderate COPD patients. (C) 2017 Elsevier Ltd and European Society

BackgroundAn analysis of cardiac injury markers in patients with OSA who sustain an episode of acute coronary syndrome (ACS) may contribute to a better understanding of the interactions and impact of OSA in subjects with ACS. We compared peak cardiac troponin I (cTnI) levels in patients with OSA and patients without OSA who were admitted for ACS.MethodsBlood samples were collected every 6 hours from the time of admission until two consecutive assays showed a downward trend in the cTnI assay. The highest value obtained defined the peak cTnI value, which provides an estimate of infarct size.ResultsWe included 89 patients with OSA and 38 patients without OSA with an apnea-hypopnea index of a median of 32 (interquartile range [IQR], 20.8-46.6/h and 4.8 [IQR, 1.6-9.6]/h, respectively. The peak cTnI value was significantly higher in patients without OSA than in patients with OSA (median, 10.7 ng/mL [IQR, 1.78-40.1 ng/mL] vs 3.79 ng/mL [IQR, 0.37-24.3 ng/mL]; P = .04). The multivariable linear regression analysis of the relationship between peak cTnI value and patient group, age, sex, and type of ACS showed that the presence or absence of OSA significantly contributed to the peak cTnI level, which was 54% lower in patients with OSA than in those without OSA.ConclusionsThe results of this study suggest that OSA has a protective effect in the context of myocardial infarction and that patients with OSA may experience less severe myocardial injury. The possible role of OSA in cardioprotection should be explored in future studies.

Upotreba kardijalnih biomarkera u prognostičke svrhe široko je ispitivana u opštoj populaciji i populaciji bolesnika na hemodijalizi, ali ne i kod bolesnika u ranijim stadijumima hronične bubrežne slabosti (HBS). Cilj naše studije bio je određivanje prognostičke vrednosti kardijalnih biomarkera [B tipa natriuretskog peptida (BNP-a), njegovog neaktivnog aminoterminalnog fragmenta (NTproBNP-a), troponina T (TnT), troponina I (TnI) i visokosenzitivnog C-reaktivnog proteina (hsCRP-a)] za kardiovaskularni mortalitet kod asimptomatskih predijaliznih bolesnika sa IV i V stadijumom HBS. Istraživanjem je obuhvaćen 61 bubrežni bolesnik (34 M, prosečne starosti 62,6±13,6 godina, GFR 15,8±5,7 ml/min). Svaki ispitanik je podvrgnut kliničkoj proceni, laboratorijskom ispitivanju, ehokardiografskom pregledu i ultrazvučnom pregledu karotidnih arterija. Tokom perioda praćenja bolesnika (medijana: 28 meseci), zabeleženo je 18 smrtnih ishoda, od čega 9 kardiovaskularnog porekla. U multivarijantnoj Cox regresionoj analizi, nezavisnu prediktivnu vrednost za kardiovaskularni mortalitet pokazali su: BNP (p=0,004), aortne kacifikacije (p=0,005), TnT (0,018) i s-urea (p=0,046). Optimalna cut off vrednost BNP-a za predviđanje kardiovaskularnog mortaliteta iznosila je 220,8 pg/ml, sa senzitivnošću 85,7% i specifičnošću 78% (AUC= 0,831; p=0,005), dok se cut off vrednost TnT 0,05 ng/ml pokazala takođe značajnom, sa senzitivnošću 77,8% i specifičnošću 78,8% (AUC=0.798; p=0.005). Stratifikovana analiza Kaplan-Meyer-ovih kriva pokazala je statistički značajnu razliku između bolesnika sa različitim nivoima BNP-a (p=0.024), TnT (p=0.001) i NTproBNP-a (p=0.033) u odnosu na kardiovaskularno preživljavanje. Kao nezavisni prediktori kardiovaskularnog mortaliteta, BNP-a i TnT mogu poslužiti u svrhu stratifikacije KV rizika kod asimptomatskih bolesnika sa uznapredovalom HBS, koji još nisu započeli lečenje dijalizom., The use of cardiac biomarkers in prognostic purposes has been widely studied in the general population and the population of hemodialysis patients but not in patients with early-stage chronic kidney disease (peptide (BNP), N-terminal fragment of BNP (NTproBNP-a), troponin T (TnT), troponin I (TnI) CKD). The aim of this study was to determine the prognostic value of cardiac biomarkers [B-type natriuretic and highly sensitive C-reactive protein (hsCRP -a)] for cardiovascular mortality in asymptomatic predialysis CKD patients, stage IV and V. The study included 61 CKD patients (34 M, average age 62.6 ± 13.6 years, GFR 15.8±5.7 ml/min). All subjects underwent clinical evaluation, laboratory testing, echocardiographic examination and carotid artery ultrasound examination of the carotid arteries. During the period of follow-up (median 28 months), there were 18 deaths of which 9 were cardiovascular in origin. In a multivariate Cox regression analysis, BNP (p = 0.004), aortic calcification (p = 0.005), the TnT (0.018) and serum urea (p = 0.046) showed the independent predictive value for cardiovascular mortality. The optimal cut-off value of BNP for predicting _ cardiovascular mortality rate was 220.8 pg/ml. with a sensitivity of 85.7% and specificity of 78% (AUC = 0.831; p = 0.005) while the TnT cut off value of 0.05 ng / ml was also found to be significant with a sensitivity of 77.8% and a specificity of 78.8% (AUC = 0.798; p = 0.005). In stratified analysis, Kaplan-Meier curves showed _statistically significant differences in cardiovascular survival in patients with different levels of BNP (p = 0.024), TnT (p = 0.001) and NTproBNP (p = 0.033). As independent predictors of cardiovascular mortality, BNP and TnT can be used to stratify CV risk in asymptomatic patients with advanced HBS who have not started dialysis treatments yet.

Background: The Mexican Tarahumara are accustomed to running ultra-distance races. No data exist on the acute physiological changes following ultra-distance running and physiological-biomarker associations in this population. Thus, we aimed to investigate the acute impact (≤ 24 h) on functional and biochemical changes of the cardiac muscle and biochemical changes associated with kidney function following a 63-km ultra-distance race with an altitude difference of 1800 m in Mexican Tarahumara athletes.Methods: Ten Tarahumara male athletes (mean ± SD age = 29.9 ± 6.6 years) volunteered to participate in the study. VO2max was assessed by a sub-maximal step test individually calibrated combining heart rate and accelerometry. Standard transthoracic echocardiography methodology and venipuncture blood tests were carried out at four time points: pre-race, immediately post-race, 6 h, and 24 h post-race.Results: Estimated mean VO2max was 54.5 (± 8.8) mL O2 min−1 kg−1 and average physiological activity intensity was 746 (± 143) J min−1 kg −1 (~ 11.5 METs). When compared to pre-race values, significant changes in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (− 15%, p < 0.001 for both parameters), cardiac output (39%, p < 0.001), and maximal longitudinal velocity (− 13%, p < 0.009) were seen post-race with LVEF also being decreased at < 6 h post-race (− 8%, p < 0.014). Plasma biomarkers mid-regional pro-atrial natriuretic peptide, copeptin-ultra sensitive, and high-sensitivity cardiac troponin T remained significantly elevated at 24 h post-race, and the two latter were inversely associated with LVEF (p < 0.04). Kidney dysfunction was indicated by increased post-race copeptin-ultra sensitive.Conclusions: The athletes participating in this study had acute transient cardiac dysfunction as assessed by echocardiography but elevated cardiac and kidney biomarkers at 24 h following a 63-km race with extreme altitude varia

Background: Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate. Methods and Results: According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes. Conclusions: In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score rem

The majority of patients with end stage renal disease die of cardiovascular causes. Comorbid conditions like diabetes and hypertension are shared by both chronic kidney disease (CKD) and cardiovascular disease. To help physicians to identify high risk CKD patients, there is a need of sensitive biomarker to detect subclinical cardiac abnormalities in the early stages of CKD to permit initiation of necessary therapeutic intervention.CKD results in several alterations in cardiovascular structure and function. We hypothesized that left atrial (LA) volume and LA strain would be sensitive markers of myocardial involvement in early CKD even in the presence of co existent diabetes and hypertension. We also hypothesized that LA metrics would be more sensitive parameters than LV parameters. We further hypothesized that LA metrics may be more sensitive than the measurement of N terminal brain naturetic peptide (NT- ProBNP) to detect myocardial dysfunction in CKD patients.To prove these congruent hypotheses, we recruited three groups of patients; the first group comprised of stage 3 CKD patients (30-59mL/min/1.73m2) with or without hypertension and or diabetes but without any previous cardiac events. Control groups were age and sex matched subjects with hypertension and or diabetes with normal renal function, without any previous cardiac history and the third group comprised of healthy adults. We additionally studied patients with diabetes and hypertension without CKD, to examine the independent effect of these conditions on LA parameters.We found that LA metrics were significantly reduced in both the CKD group and the risk factor matched control group, compared with normal subjects. Importantly, LA metrics were significantly altered in CKD patients compared to risk factor matched subjects indicating these parameters are sensitive markers to detect myocardial involvement despite the presence of coexistent hypertension and diabetes. LA volume and strain also showed incremental v

Background: The Mexican Tarahumara are accustomed to running ultra-distance races. No data exist on the acute physiological changes following ultra-distance running and physiological-biomarker associations in this population. Thus, we aimed to investigate the acute impact (≤ 24 h) on functional and biochemical changes of the cardiac muscle and biochemical changes associated with kidney function following a 63-km ultra-distance race with an altitude difference of 1800 m in Mexican Tarahumara athletes.Methods: Ten Tarahumara male athletes (mean ± SD age = 29.9 ± 6.6 years) volunteered to participate in the study. VO2max was assessed by a sub-maximal step test individually calibrated combining heart rate and accelerometry. Standard transthoracic echocardiography methodology and venipuncture blood tests were carried out at four time points: pre-race, immediately post-race, 6 h, and 24 h post-race.Results: Estimated mean VO2max was 54.5 (± 8.8) mL O2 min−1 kg−1 and average physiological activity intensity was 746 (± 143) J min−1 kg −1 (~ 11.5 METs). When compared to pre-race values, significant changes in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (− 15%, p < 0.001 for both parameters), cardiac output (39%, p < 0.001), and maximal longitudinal velocity (− 13%, p < 0.009) were seen post-race with LVEF also being decreased at < 6 h post-race (− 8%, p < 0.014). Plasma biomarkers mid-regional pro-atrial natriuretic peptide, copeptin-ultra sensitive, and high-sensitivity cardiac troponin T remained significantly elevated at 24 h post-race, and the two latter were inversely associated with LVEF (p < 0.04). Kidney dysfunction was indicated by increased post-race copeptin-ultra sensitive.Conclusions: The athletes participating in this study had acute transient cardiac dysfunction as assessed by echocardiography but elevated cardiac and kidney biomarkers at 24 h following a 63-km race with extreme altitude varia

Introduction: Breast cancer is the most frequent cancer affecting women worldwide. In every setting, the majority of women are treated with an evergrowing arsenal of therapeutic agents that have greatly improved their outcomes. However, these therapies can also be associated with significant adverse events. Areas covered: This review aims to thoroughly describe the current state of the evidence regarding the potential cardiotoxicity of agents commonly used in the treatment of breast cancer. These include chemotherapeutic agents, anti-HER2 therapies and CDK4/6 and mTOR inhibitors. Furthermore, issues related to the risk stratification and monitoring tools are explored. Expert opinion: Anthracycline- and trastuzumab-related cardiac toxicities have been extensively studied. Substantial evidence is now available concerning additional anti-HER2 agents such as pertuzumab, T-DM1 and tyrosine kinase inhibitors; overall, the cardiotoxicity profile is reassuring. Cardiac events due to endocrine therapy are mostly ischemic and, in the context of prolonged therapy, need specific attention. Novel agents implicated in the treatment of hormone receptor-positive disease are potentially arrhythmogenic and the exact risk will need to be further refined. As for today, assessment of baseline risk factors prior to treatment initiation and cardiac imaging before and during treatment remains the optimal way to prevent cardiac dysfunction. Cardioprotective therapy in primary prevention is still a matter of debate., SCOPUS: re.j, info:eu-repo/semantics/published

Aims: The aim of this study was to evaluate the presence, localisation and extent of myocardial injury as determined by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: A total of 37 patients, who underwent successful TAVI with a balloon-expandable valve (transapical [TA], n=11; non-TA, n=26), were included. Cardiac biomarker (CK-MB and cTnT) levels were determined at baseline and following TAVI. CMR was performed within a week before and within 30 days following TAVI. Some increase in cardiac biomarkers was detected in 97% of the patients as determined by a rise in cTnT, and in 49% of the patients as determined by a rise in CK-MB. Following TAVI, no new myocardial necrosis defects were observed with the non-TA approach. Nonetheless, all patients who underwent TAVI through the TA approach had new focal myocardial necrosis in the apex, with a median myocardial extent and necrotic mass of 5% [2.0-7.0] and 3.5 g [2.3-4.5], respectively. Conclusions: Although some increase in cardiac biomarkers of myocardial injury was systematically detected following TAVI, new myocardial necrosis as evaluated by CMR was observed only in patients undergoing the procedure through the TA approach, involving ~5% of the myocardium in the apex.

BACKGROUND : Cardiac biomarker release signifying myocardial injury post-transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of valve and procedural approaches is unknown. OBJECTIVES : This study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR. METHODS : This multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up. RESULTS : Overall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold [interquartile range (IQR): 0.9 to 2.8-fold]). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (p < 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (p < 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 [IQR: 8 to 36] months) overall and cardiovascular mortality (p < 0.001 for all). Any increase in CK-MB levels was associated with poorer clinical outcomes, and there was a stepwise rise in late mortality according to the various degrees of CK-MB increase after TAVR (p < 0.001). CONCLUSIONS : Some degree of myocardial injury was detected in two-thirds of patients post TAVR, especially in those undergoing TA-TAVR or presenting with major procedural complications. A greater rise in CK-MB levels associated with greater acute and late mortality, imparting a negative impact on left ventricula

Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA) and dynophysistoxins (DTXs) are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP). Yessotoxins (YTXs) are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from several countries have regulated the content of DSPs and YTXs in shellfish to protect human health. In mice, OA and YTX have been associated with ultrastructural heart damage in vivo. Therefore, this study explored the potential of OA, DTX-1 and YTX to cause acute heart toxicity. Cardiotoxicity was evaluated in vitro by measuring hERG (human èter-a-go-go gene) channel activity and in vivo using electrocardiogram (ECG) recordings and cardiac damage biomarkers. The results demonstrated that these toxins do not exert acute effects on hERG channel activity. Additionally, in vivo experiments showed that these compounds do not alter cardiac biomarkers and ECG in rats acutely. Despite the ultrastructural damage to the heart reported for these toxins, no acute alterations of heart function have been detected in vivo, suggesting a functional compensation in the short term

BACKGROUND : Cardiac biomarker release signifying myocardial injury post-transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of valve and procedural approaches is unknown. OBJECTIVES : This study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR. METHODS : This multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up. RESULTS : Overall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold [interquartile range (IQR): 0.9 to 2.8-fold]). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (p < 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (p < 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 [IQR: 8 to 36] months) overall and cardiovascular mortality (p < 0.001 for all). Any increase in CK-MB levels was associated with poorer clinical outcomes, and there was a stepwise rise in late mortality according to the various degrees of CK-MB increase after TAVR (p < 0.001). CONCLUSIONS : Some degree of myocardial injury was detected in two-thirds of patients post TAVR, especially in those undergoing TA-TAVR or presenting with major procedural complications. A greater rise in CK-MB levels associated with greater acute and late mortality, imparting a negative impact on left ventricula

Aims: The aim of this study was to evaluate the presence, localisation and extent of myocardial injury as determined by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging in patients undergoing transcatheter aortic valve implantation (TAVI). Methods and results: A total of 37 patients, who underwent successful TAVI with a balloon-expandable valve (transapical [TA], n=11; non-TA, n=26), were included. Cardiac biomarker (CK-MB and cTnT) lev- els were determined at baseline and following TAVI. CMR was performed within a week before and within 30 days following TAVI. Some increase in cardiac biomarkers was detected in 97% of the patients as deter- mined by a rise in cTnT, and in 49% of the patients as determined by a rise in CK-MB. Following TAVI, no new myocardial necrosis defects were observed with the non-TA approach. Nonetheless, all patients who underwent TAVI through the TA approach had new focal myocardial necrosis in the apex, with a median myo-cardial extent and necrotic mass of 5% [2.0-7.0] and 3.5 g [2.3-4.5], respectively. Conclusions: Although some increase in cardiac biomarkers of myocardial injury was systematically detected following TAVI, new myocardial necrosis as evaluated by CMR was observed only in patients undergoing the procedure through the TA approach, involving ~5% of the myocardium in the apex.

Background: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. Objective: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. Methods: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomaiters Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90 mL/min/1.73 m(2). Results: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a CUR of 15 mL/mM/1.73 m(2) varied from 2-fold to 15 fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured CUR and increased more at low CUR compared to hs-cTnI. For hFABP and NT-proBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations) Conclusion: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd,40/).

[Abstract] INTRODUCTION: Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data from longitudinal studies of diastolic dysfunction (DD) in this group of patients are scarce. The objective of the present study was to assess the incidence, evolution, and predictors of DD in patients with breast cancer treated with anthracyclines. METHODS: This analytical, observational cohort study comprised 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) for breast cancer. All patients underwent clinical evaluation, echocardiogram, and measurement of cardiac biomarkers at baseline, end of anthracycline-based CHT, and at 3 months and 9 months after anthracycline-based CHT was completed. Fifteen patients receiving trastuzumab were followed with two additional visits at 6 and 12 months after the last dose of anthracycline-based CHT. A multivariate analysis was performed to find variables related to the development of DD. Fifteen of the 100 patients had baseline DD and were excluded from this analysis. RESULTS: At the end of follow-up (median: 12 months, interquartile range: 11.1-12.8), 49 patients (57.6%) developed DD. DD was persistent in 36 (73%) but reversible in the remaining 13 patients (27%). Four patients developed cardiotoxicity (three patients had left ventricular systolic dysfunction and one suffered a sudden cardiac death). None of the patients with normal diastolic function developed systolic dysfunction during follow-up. In the logistic regression model, body mass index (BMI) and age were independently related to the development of DD, with the following odds ratio values: BMI: 1.19 (95% confidence interval [CI]: 1.04-1.36), and age: 1.12 (95% CI: 1.03-1.19). Neither cardiac biomarkers nor remaining clinical variables were predictors of DD. CONCLUSION: Development of diastolic dysfunction after treatment with anthracycline or anthracycline- plus trastuzumab chemotherapy is common. B

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both car

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both car

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both car

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both car

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both car

Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value. The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months. Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both car

U kliničkoj praksi koristi se nekoliko skorova za procenu rizika od pojaverazličitih oblika kardiovaskularnih bolesti (KVB) koji se zasnivaju na multivarijabilnimregresionim jednačinama izvedenim iz rezultata praćenja različitih kohortnih grupa. Naosnovu prisustva tradicionalnih faktora rizika [hiperholesterolemija, hipertenzija, pol,starost, porodična istorija KVB, dijabetes i pušenje] definisanim algoritmima seizračunava apsolutni 10-godišnji rizik za koronarnu bolest srca (KBS) na osnovuFramingamskog rizik skora (FRS), 10-godišnji rizik od svih oblika KVB – tzv. „globalniKVB rizik“ (globalni FRS), kao i dugoročni (30-godišnji) rizik za KVB.Ateroskleroza je bolest uslovljena brojnim faktorima koju prati hroničnainflamacija niskog intenziteta i dislipidemija. Zahvaljujući velikom broju postojećihdokaza da C-reaktivni protein (CRP) snažno i nezavisno predviđa pojavukardiovaskularnih komplikacija, primena CRP-a u kliničkoj praksi definisana je odstrane nekoliko organizacija. Za proces ateroskleroze karakteristična je hroničnainflamacija gde su koncentracije CRP-a u cirkulaciji niže od granice detekcijekonvencionalnih testova. Određivanje tako niskih nivoa CRP-a zahteva testove savećom analitičkom osetljivošću, koji se označavaju kao visoko osetljivi (highsensitivity,hs), a na ovaj način određena koncentracija CRP-a kao „visoko osetljiviCRP“ (hsCRP). Takođe, postoje podaci i o drugim faktorima koji doprinose održavanjuinflamacije ili odražavaju intenzitet aterosklerotskih procesa i koji bi mogli daidentifikuju doprinos kardiovaskularnom riziku koji ne potiče od tradicionalnih faktorarizika, kao što su mokraćna kiselina, jačina glomerularne filtracije procenjena na osnovukoncentracije kreatinina ili cistatina C (eGFR), amino-terminalni pro-natriuretičkipeptid tipa B (NT-proBNP), srčani troponin (cTn).Cilj rada bio je da se ispita da li postoji povezanost između hsCRP-a,ustanovljenog biomarkera proaterogenog metaboličkog stanja, i drugih biomarkerainflamacije [serumski, Several risk score algorithms for cardiovascular risk assessment based onmultivariable regression equations derived from different cohorts are being used inclinical practice. According to presence of traditional risk factors [hypercholesterolemia,hypertension, gender, age, family history of premature cardiovascular disease (CVD),diabetes and cigarette smoking], absolute 10-year risk for coronary heart disease (CHD)according to Framingham risk score (FRS), 10-year risk for cardiovascular disease ingeneral – „global CVD risk“ using global FRS, and long term (30-year) CVD risk arebeing calculated.Atherosclerosis is a disease conditioned with multiple factors followed bychronic low-grade inflammation and dyslipidemia. Thanks to substantial evidence thatC-reactive protein (CRP) strongly and independently predicts cardiovascularcomplications, the use of CRP in clinical practice is recommended by severalinstitutions. Atherosclerosis process is characterized with chronic inflammation wherecirculating CRP concentrations are lower than limit of detection of conventional assays.For measuring such low CRP levels high-sensitivity (hsCRP) assays have beendeveloped. Also, there are evidence of other factors, contributing to and maintaining theintensity of atherosclerotic processes, which might identify cardiovascular riskcontribution not originated from traditional risk factors. These are uric acid, estimatedglomerular filtration rate (eGFR) based on creatinine or cystatin C, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin (cTn).The aim of this study was to examine whether there is association betweenhsCRP, as the established marker of proaterogenic metabolic state, and other biomarkersof inflammation [serum amyloid A (SAA), fibrinogen, α1-acid glycoprotein (A1AGP),haptoglobin, C3 and C4 complement components), lipid metabolism [total, HDL, non-HDL and LDL cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B(apo B), lipoprotein (a)

U kliničkoj praksi koristi se nekoliko skorova za procenu rizika od pojave različitih oblika kardiovaskularnih bolesti (KVB) koji se zasnivaju na multivarijabilnim regresionim jednačinama izvedenim iz rezultata praćenja različitih kohortnih grupa. Na osnovu prisustva tradicionalnih faktora rizika [hiperholesterolemija, hipertenzija, pol, starost, porodična istorija KVB, dijabetes i pušenje] definisanim algoritmima se izračunava apsolutni 10-godišnji rizik za koronarnu bolest srca (KBS) na osnovu Framingamskog rizik skora (FRS), 10-godišnji rizik od svih oblika KVB – tzv. „globalni KVB rizik“ (globalni FRS), kao i dugoročni (30-godišnji) rizik za KVB. Ateroskleroza je bolest uslovljena brojnim faktorima koju prati hronična inflamacija niskog intenziteta i dislipidemija. Zahvaljujući velikom broju postojećih dokaza da C-reaktivni protein (CRP) snažno i nezavisno predviđa pojavu kardiovaskularnih komplikacija, primena CRP-a u kliničkoj praksi definisana je od strane nekoliko organizacija. Za proces ateroskleroze karakteristična je hronična inflamacija gde su koncentracije CRP-a u cirkulaciji niže od granice detekcije konvencionalnih testova. Određivanje tako niskih nivoa CRP-a zahteva testove sa većom analitičkom osetljivošću, koji se označavaju kao visoko osetljivi (highsensitivity, hs), a na ovaj način određena koncentracija CRP-a kao „visoko osetljivi CRP“ (hsCRP). Takođe, postoje podaci i o drugim faktorima koji doprinose održavanju inflamacije ili odražavaju intenzitet aterosklerotskih procesa i koji bi mogli da identifikuju doprinos kardiovaskularnom riziku koji ne potiče od tradicionalnih faktora rizika, kao što su mokraćna kiselina, jačina glomerularne filtracije procenjena na osnovu koncentracije kreatinina ili cistatina C (eGFR), amino-terminalni pro-natriuretički peptid tipa B (NT-proBNP), srčani troponin (cTn). Cilj rada bio je da se ispita da li postoji povezanost između hsCRP-a, ustanovljenog biomarkera proaterogenog metaboličkog stanja, i drugih biomarke, Several risk score algorithms for cardiovascular risk assessment based on multivariable regression equations derived from different cohorts are being used in clinical practice. According to presence of traditional risk factors [hypercholesterolemia, hypertension, gender, age, family history of premature cardiovascular disease (CVD), diabetes and cigarette smoking], absolute 10-year risk for coronary heart disease (CHD) according to Framingham risk score (FRS), 10-year risk for cardiovascular disease in general – „global CVD risk“ using global FRS, and long term (30-year) CVD risk are being calculated. Atherosclerosis is a disease conditioned with multiple factors followed by chronic low-grade inflammation and dyslipidemia. Thanks to substantial evidence that C-reactive protein (CRP) strongly and independently predicts cardiovascular complications, the use of CRP in clinical practice is recommended by several institutions. Atherosclerosis process is characterized with chronic inflammation where circulating CRP concentrations are lower than limit of detection of conventional assays. For measuring such low CRP levels high-sensitivity (hsCRP) assays have been developed. Also, there are evidence of other factors, contributing to and maintaining the intensity of atherosclerotic processes, which might identify cardiovascular risk contribution not originated from traditional risk factors. These are uric acid, estimated glomerular filtration rate (eGFR) based on creatinine or cystatin C, amino-terminal pro- B-type natriuretic peptide (NT-proBNP), cardiac troponin (cTn). The aim of this study was to examine whether there is association between hsCRP, as the established marker of proaterogenic metabolic state, and other biomarkers of inflammation [serum amyloid A (SAA), fibrinogen, α1-acid glycoprotein (A1AGP), haptoglobin, C3 and C4 complement components), lipid metabolism [total, HDL, non- HDL and LDL cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B

Background—Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Methods and Results—Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS2 and CHA2DS2-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio [HR], 1.99 [95% CI, 1.17–3.39]; P=0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups, (HR, 2.40 [95% CI, 1.41–4.07]; P=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05–6.29]; P<0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73 [3.95–11.49]; P<0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, P<0.0001, for a composite of thromboembolic events. Conclusions—Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables.

The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic veloc, Physiology of Adventure Racing

This thesis examines the relationship between cardiovascular disease and end stage kidney disease (ESKD) and the high cardiovascular risk patients with ESKD endure. To illustrate this risk, we assessed outcomes following coronary artery bypass graft surgery. A forty-fold increase in the mortality rate in the early post-operative period, in addition to an appreciably increased rate of post-operative complications, was observed in patients with significantly impaired pre-operative kidney function (glomerular filtration rate < 30 ml/min/1.73m2), compared to those with normal kidney function. Kidney failure itself, owing to its range of unique, “non-traditional” risk factors, contributes to this heightened cardiovascular risk. Cardiac biomarker and imaging abnormalities have been shown to predict inferior cardiovascular outcomes in ESKD patients; however the precise pathophysiology underlying this cardiovascular disease is poorly understood. We compared the powerful novel cardiac imaging technique, cardiac magnetic resonance imaging (cMRI), with standard cardiac imaging modalities, to assess myocardial ischaemia and LV function and morphology and correlated these results with cardiac biomarkers. The enhanced imaging capabilities of cMRI were mitigated by the emergence of a causative association between the development of Nephrogenic Systemic Fibrosis (NSF) and the administration of gadolinium based contrast agents (GBCA). This development, which occurred in the early stages of the study, instigated a retrospective review to further delineate the risk NSF which resulted in the development of guidelines for the use of GBCAs and a change in this study’s cMRI protocol precluding GBCAs. Notably, in asymptomatic participants, myocardial ischaemia was detected more frequently by cMRI (despite not administering GBCAs) than standard imaging. Left ventricular (LV) diastolic dysfunction was identified in the majority of participants on transthoracic echocardiography (TTE) and was

Background: High-sensitivity cardiac troponin assays are being introduced clinically for earlier diagnosis of acute myocardial infarction (AMI). We evaluated the analytical performance of a high-sensitivity cardiac troponin T assay (hscTnT. Roche Diagnostics) in a multicenter, international trial. Methods: Three US and 5 European sites evaluated hscTnT on the Modular (R) Analytics E170, cobas (R) 6000, Elecsys 2010, and cobas (R) e 411. Precision, accuracy, reportable range, an inter-laboratory comparison trial, and the 99th percentile of a reference population were assessed. Results: Total imprecision (CVs) were 4.6-36.8% between 3.4 and 10.3 ng/L hscTnT. Assay linearity was up to 10,000 ng/L and the limit of blank and detection were 3 and 5 ng/L, respectively. The 99th percentile reference limit was 14.2 ng/L (n = 533). No significant differences between specimen types, assay incubation time, or reagent lots existed. A substantial positive bias (76%) exists between the 4th generation and hscTnT assays at the low end of the measuring range (< 50 ng/L). hscTnT serum pool concentrations were within 2SD limits of the mean of means in the comparison trial, indicating comparable results across multiple platforms and laboratories. Conclusion: The Roche hscTnT assay conforms to guideline precision requirements and will likely identify additional patients with myocardial injury suspicious for AMI.

The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic veloc, Physiology of Adventure Racing

The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic veloc, Physiology of Adventure Racing

The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic veloc, Physiology of Adventure Racing

The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic veloc, Physiology of Adventure Racing

The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply-demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.