Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial.

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking ß blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. FUNDING: British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

Perioperative kinetics of endocan in patients undergoing cardiac surgery with and without cardiopulmonary bypass.

INTRODUCTION: Endothelial Specific Molecule-1 or endocan is a novel biomarker associated with the development of acute lung injury (ALI) in response to a systemic inflammatory state such as trauma. Acute Respiratory Distress syndrome (ARDS), a severe form of ALI is a devastating complication that can occur following cardiac surgery due to risk factors such as the use of cardiopulmonary bypass (CPB) during surgery. In this study we examine the kinetics of endocan in the perioperative period in cardiac surgical patients. METHODS: After ethics approval, we obtained informed consent from 21 patients undergoing elective cardiac surgery (3 groups with seven patients in each group: coronary artery bypass grafting (CABG) with the use of CPB, off-pump CABG and complex cardiac surgery). Serial blood samples for endocan levels were taken in the perioperative period (T0: baseline prior to induction, T1: at the time of heparin administration, T2: at the time of protamine, T2, T3, T4 and T5 at 1, 2, 4 and 6h following protamine administration respectively). Endocan samples were analysed using the enzyme-linked immunosorbent assay (ELISA) method. Statistical analysis incorporated the use of test for normality. RESULTS: Our results reveal that an initial rise in the levels of serum endocan from baseline in all patients after induction of anaesthesia. Patients undergoing off-pump surgery have lower endocan concentrations in the perioperative period than those undergoing CPB. Endocan levels decrease following separation from CPB, which may be attributed to haemodilution following CPB. Following administration of protamine, endocan concentrations steadily increased in all patients, reaching a steady state between 2 and 6h. The baseline endocan concentrations were elevated in patients with hypertension and severe coronary artery disease. CONCLUSION: Baseline endocan concentrations are higher in hypertensive patients with critical coronary artery stenosis. Endocan concentrations increased after induction of anaesthesia and decreased four hours after separation from CPB. Systemic inflammation may be responsible for the rise in endocan levels following CPB.

The interaction between systemic inflammation and psychosocial stress in the association with cardiac troponin elevation: A new approach to risk assessment and disease prevention.

We have previously shown that there is a complex and dynamic biological interaction between acute mental stress and acute release of inflammatory factors into the blood stream in relation to heart disease. We now hypothesize that the presence of chronic psychosocial stress may modify the weight of single test results for inflammation as a predictor of heart disease. Using a cross-sectional design, 500 participants free from heart disease drawn from the Whitehall II study in UK in 2006-2008 were tested for plasma fibrinogen as an inflammatory factor, financial strain as a marker of chronic psychosocial stress, coronary calcification measured using computed tomography, and for plasma high-sensitivity cardiac troponin T (HS-CTnT) as a marker of cardiac risk. Fibrinogen concentration levels above the average were associated with a 5-fold increase in the odds of HS-CTnT positivity only among individuals with financial strain (N=208, OR=4.73, 95%CI=1.67 to 13.40, P=0.003). Fibrinogen was in fact not associated with HS-CTnT positivity in people without financial strain despite the larger size of that subsample (n=292, OR=0.84, 95%CI=0.42 to 1.67, P=0.622). A test for interaction on the full sample (N=500) showed a P value of 0.010 after adjusting for a range of demographics, health behaviours, traditional cardiovascular risk factors, psychosocial stressors, inflammatory cytokines, and coronary calcification. In conclusion, elevated fibrinogen seems to be cardio-toxic only when is combined with financial strain. Chronic psychosocial stress may modify the meaning that we should give to single test results for inflammation. Further research is needed to confirm our results.

The mediation of coronary calcification in the association between risk scores and cardiac troponin T elevation in healthy adults: Is atherosclerosis a good prognostic precursor of coronary disease?

BACKGROUND: Conventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease. In UK in 2006-2008 (Whitehall II study) we tested the ability of several risk scores to identify individuals with cardiac cell damage and assessed to what extent their estimates were mediated by the presence of atherosclerosis. METHODS: 430 disease-free, low-risk participants were tested for high-sensitivity cardiac troponin-T (HS-CTnT) and for coronary calcification using electron-beam, dual-source, computed tomography (CAC). We analysed the data cross-sectionally using ROC curves and mediation tests. RESULTS: When the risk scores were ranked according to the magnitude of ROC areas for HS-CTnT prediction, a score based only on age and gender came first (ROC area=0.79), followed by Q-Risk2 (0.76), Framingham (0.70), Joint-British-Societies (0.69) and Assign (0.68). However, when the scores were ranked according to the extent of mediation by CAC (proportion of association mediated), their order was essentially reversed (age&gender=6.8%, Q-Risk2=9.7%, Framingham=16.9%, JBS=17.8%, Assign=17.7%). Therefore, the more accurate a score is in predicting detectable HS-CTnT, the less it is mediated by CAC; i.e. the more able a score is in capturing atherosclerosis the less it is able to predict cardiac damage. The P for trend was 0.009. CONCLUSIONS: The dynamics through which cardiac cell damage is caused cannot be explained by 'classic' heart disease risk factors alone. Further research is needed to identify precursors of heart disease other than atherosclerosis.

Investigating the Effect of a Single Infusion of Reconstituted High-Density Lipoprotein in Patients with Symptomatic Carotid Plaques.

BACKGROUND: Elevation of plasma high-density lipoprotein (HDL) cholesterol concentration reduces cardiovascular mortality and morbidity. HDLs have been shown to possess acute anti-inflammatory, antioxidant, and antithrombotic properties. We hypothesize that HDL therapy can acutely alter local and systemic manifestations of plaque instability. METHODS: Forty patients with early symptomatic carotid disease were randomized to either receive reconstituted HDL (rHDL) 40 mg/kg (n = 20) or placebo (n = 20). Carotid endarterectomies were performed 24 hr later. Plaques were obtained intraoperatively and used for measurement of thrombomodulatory genes expression. Plasma samples were collected before the infusion, 24 and 48 hr later to measure changes in systemic markers of plaque instability. RESULTS: No significant differences were noted in thrombomodulatory genes expression between the 2 groups. Systemic levels of tissue factor, matrix metalloproteinase 9 (MMP-9), and monocyte chemotactic factor-1 (MCP-1) were significantly reduced in the rHDL group. However, the effects on MMP-9 and MCP-1 were abolished in the immediate postoperative period. Although rHDL did not affect plasma interleukin-6 levels 24 hr following the infusion, it prevented the significant postoperative elevation seen in the placebo group. CONCLUSIONS: A single infusion of rHDL can acutely alter plasma biomarkers associated with plaque instability and cardiovascular morbidity.

Effects of seated and standing cold water immersion on recovery from repeated sprinting.

This study investigated the effects of two different hydrostatic pressures (seated or standing) during cold water immersion at attenuating the deleterious effects of strenuous exercise on indices of damage and recovery. Twenty four male well-trained games players (age 23 ± 3 years; body mass 81.4 ± 8.7 kg: [Formula: see text]O2max 57.5 ± 4.9 ml∙kg(-1)∙min(-1)) completed the Loughborough Intermittent Shuttle Test (LIST) and were randomly assigned to either a control, seated cold water immersion or a standing cold water immersion (14 min at 14°C). Maximal isometric voluntary contraction, counter-movement jump, creatine kinase, C-reactive protein, interleukin-6 and delayed onset muscle soreness (DOMS) were measured before and up to 72 h following the LIST. All dependent variables showed main effects for time (P < 0.05) following the LIST, indicating physiological stress and muscle damage following the exercise. There were no significant group differences between control and either of the cold water immersion interventions. Seated cold water immersion was associated with lower DOMS than standing cold water immersion (effect size = 1.86; P = 0.001). These data suggest that increasing hydrostatic pressure by standing in cold water does not provide an additional recovery benefit over seated cold water immersion, and that both seated and standing immersions have no benefit in promoting recovery following intermittent sprint exercise.

Analytical evaluation of the automated galectin-3 assay on the Abbott ARCHITECT immunoassay instruments.

BACKGROUND: Galectin-3 is secreted from macrophages and binds and activates fibroblasts forming collagen. Tissue fibrosis is central to the progression of chronic heart failure (CHF). We performed a European multicentered evaluation of the analytical performance of the two-step routine and Short Turn-Around-Time (STAT) galectin-3 immunoassay on the ARCHITECT i1000SR, i2000SR, and i4000SR (Abbott Laboratories). METHODS: We evaluated the assay precision and dilution linearity for both routine and STAT assays and compared serum and plasma, and fresh vs. frozen samples. The reference interval and biological variability were also assessed. Measurable samples were compared between ARCHITECT instruments and between the routine and STAT assays and also to a galectin-3 ELISA (BG Medicine). RESULTS: The total assay coefficient of variation (CV%) was 2.3%-6.2% and 1.7%-7.4% for the routine and STAT assays, respectively. Both assays demonstrated linearity up to 120 ng/mL. Galectin-3 concentrations were higher in plasma samples than in serum samples and correlated well between fresh and frozen samples (R=0.997), between the routine and STAT assays, between the ARCHITECT i1000 and i2000 instruments and with the galectin-3 ELISA. The reference interval on 627 apparently healthy individuals (53% male) yielded upper 95th and 97.5th percentiles of 25.2 and 28.4 ng/mL, respectively. Values were significantly lower in subjects younger than 50 years. CONCLUSIONS: The galectin-3 routine and STAT assays on the Abbott ARCHITECT instruments demonstrated good analytical performance. Further clinical studies are required to demonstrate the diagnostic and prognostic potential of this novel marker in patients with CHF.

Elevation of plasma high-density lipoproteins inhibits development of experimental abdominal aortic aneurysms.

OBJECTIVE: Patients with abdominal aortic aneurysms have lower concentrations of high-density lipoproteins (HDLs), leading us to investigate whether increasing plasma HDLs could influence aneurysm formation. METHODS AND RESULTS: Using the angiotensin II-induced hypercholesterolemic and the CaCl(2)-induced normocholesterolemic mouse model of AAA, we investigated the hypothesis that elevation of HDLs inhibits AAA. HDLs elevated before or at the time of AAA induction reduced AAA formation in both models but had no effect on early ruptures. Analysis of protein lysates from specific aortic segments demonstrated site-specific effects of HDLs on early signal transduction and cellular attrition. We found that HDLs reduced extracellular signal related kinases 1/2 activation in the suprarenal segment, while having no effect on p38 mitogen-associated protein kinase activation in any aortic segment and inhibiting c-Jun N-terminal kinase activation in all aortic segments. In addition, HDL elevation inhibited angiotensin II-induced apoptosis while inducing autophagy in the suprarenal segment of the aorta. Using Illumina gene array profiling we investigated the ability of HDL to modulate basal suprarenal aortic gene expression. CONCLUSIONS: Increasing plasma HDLs inhibit experimental AAA formation, independent of hypercholesterolemia via reduced extracellular signal related kinases 1/2 activation and alteration of the balance of cellular attrition. HDLs modulate genes involved in matrix remodelling, cell migration, and proliferation.

Influence of population selection on the 99th percentile reference value for cardiac troponin assays.

OBJECTIVE: We sought to determine the effect of patient selection on the 99th reference percentile of 2 sensitive and 1 high-sensitivity (hs) cardiac troponin assays in a well-defined reference population. METHODS: Individuals>45 years old were randomly selected from 7 representative local community practices. Detailed information regarding the participants was collected via questionnaires. The healthy reference population was defined as individuals who had no history of vascular disease, hypertension, or heavy alcohol intake; were not receiving cardiac medication; and had blood pressure<140/90 mmHg, fasting blood glucose<110 mg/dL (approximately 6 mmol/L), estimated creatinine clearance>60 mL·min(-1)·(1.73 m2)(-1), and normal cardiac function according to results of echocardiography. Samples were stored at -70 °C until analysis for cardiac troponin I (cTnI) and cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide. RESULTS: Application of progressively more stringent population selection strategies to the initial baseline population of 545 participants until the only individuals who remained were completely healthy according to the study criteria reduced the number of outliers seen and led to a progressive decrease in the 99th-percentile value obtained for the Roche hs-cTnT assay and the sensitive Beckman cTnI assay but not for the sensitive Siemens Ultra cTnI assay. Furthermore, a sex difference found in the baseline population for the hs-cTnT (P=0.0018) and Beckman cTnI assays (P<0.0001) progressively decreased with more stringent population selection criteria. CONCLUSIONS: The reference population selection strategy significantly influenced the 99th percentile reference values determined for troponin assays and the observed sex differences in troponin concentrations.

Obesity, inflammation and brachial artery flow-mediated dilatation: therapeutic targets in patients with microvascular angina (cardiac syndrome X).

BACKGROUND: The pathophysiology of microvascular angina (cardiac syndrome X, CSX), (effort-induced angina, a positive response to exercise stress testing and angiographically normal coronary arteries) has not been fully elucidated. Various pathogenic mechanisms have been proposed, amongst which coronary microvascular dysfunction features prominently. Management of patients with microvascular angina is often challenging as a substantial number of patients does not respond to conventional anti-anginal therapy. In this study, we sought to assess the association between brachial artery FMD, high-sensitive C-reactive protein (hs-CRP) and cardiovascular risk factors including obesity in patients with cardiac syndrome X. METHODS AND RESULTS: Thirty-four consecutive CSX patients (29 female, mean age 60 ± 9 years) were recruited from a specialised CSX clinic. Twelve asymptomatic subjects (10 female, mean age 51 ± 12 years) with comparable cardiovascular risk factor profile served as controls. All participants underwent standardized computer-assisted FMD measurements and assessment of hs-CRP concentrations at study entry. Body mass index (BMI), used as a general measure of obesity was calculated as weight (kilograms) divided by height (meters squared). Compared to controls, CSX patients had significantly higher hs-CRP concentrations (p = 0.003) and impaired FMD (p < 0.01). Moreover, among the CSX patients, a correlation between FMD and hs-CRP (r = -0.66, p < 0.01), FMD and BMI (r = 0.377, p = 0.028), and hs-CRP and BMI (r = -0.372, p = 0.030) was found. CONCLUSION: Impaired brachial artery FMD is significantly associated with elevated hs-CRP concentrations and BMI in patients with CSX. The results support the concept that low-grade inflammation and obesity may promote vascular dysfunction in these patients representing therapeutic targets for future research investigations.

The endurance athletes heart: acute stress and chronic adaptation.

The impact of endurance exercise training on the heart has received significant research and clinical attention for well over a century. Despite this, many issues remain controversial and clinical interpretation can be complex of biomarkers of cardiomyocyte insult. This review assesses the current state of knowledge related to two areas of research where problems with clinical decision making may arise: (1) the impact of chronic endurance exercise training on cardiac structure, function and electrical activity to the point where the athletic heart phenotype may be similar to the expression of some cardiac pathologies (a diagnostic dilemma referred to as the 'grey-zone') and (2) the impact of acute bouts of prolonged exercise on cardiac function and the presentation of biomarkers and cardiomyocyte insult in the circulatory system. The combination of acute endurance exercise stress on the heart and prolonged periods of training are considered together in the final section.

Biological markers of cardiac damage are not related to measures of cardiac systolic and diastolic function using cardiovascular magnetic resonance and echocardiography after an acute bout of prolonged endurance exercise.

OBJECTIVES: Seventeen male participants (mean (SD) (range): age 33.5 (6.5) years (46-26 years), body mass 80 (9.2) kg (100-63 kg), height 1.81 (0.06) m (1.93- 1.70 m)) ran a marathon to investigate the relationship between systolic function (using cardiac magnetic resonance (CMR)) and diastolic function (using echocardiography) against biomarkers of cardiac damage. METHODS: Echocardiographic and cardiac troponin I (cTnI)/N-terminal pro-B-type natriuretic peptide (NTproBNP) data were collected 24 h premarathon, immediately postmarathon and 6 h postmarathon. CMR data were collected 24 h premarathon and at 6 h postmarathon. RESULTS: Body mass was significantly reduced postmarathon (80 (9.2) vs 78.8 (8.6) kg; p<0.001). There was a significant E/A reduction postmarathon (1.11 (0.34) vs 1.72 (0.44); p<0.05) that remained depressed 6 h postmarathon (1.49 (0.43); p<0.05). CMR demonstrated left ventricular end-diastolic and end-systolic volumes were reduced postmarathon, with a preserved stroke volume. Left ventricular ejection fraction 6 h postmarathon significantly increased (64.4% (4.2%) vs 67.4% (5%); p<0.05). There were significant elevations in cTnI (0.00 vs 0.04 (0.03) µg/l; p<0.05) and NTproBNP (37.4 (24.15) ng/l vs 59.34 (43.3) ng/l; p<0.05) immediately postmarathon. Eight runners had cTnI elevations immediately postmarathon above acute myocardial infarction cutoff levels (≥0.03 µg/l). No correlations between cTnI/NTproBNP and measures of diastolic function (E, A, E/A, isovolumic relaxation time, E deceleration time and E/E') or measures of systolic function (stroke volume or ejection fraction) were observed immediately postmarathon or 6 h postmarathon. CONCLUSIONS: Biomarkers of cardiac damage after prolonged exercise are not associated with either systolic or diastolic functional measures.

Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care.

AIMS: The study evaluated the use of age-related decision limits for N-terminal pro-B-type natriuretic peptide (NT-proBNP), for ruling out suspected systolic dysfunction in symptomatic patients in primary care, compared with the present standards. METHODS AND RESULTS: Data were obtained from 5508 patients from 10 studies in the UK, New Zealand, Europe, and USA. All have had NT-proBNP analysis and echocardiography. The median age was 62 years (range 18-100 years) with a prevalence of reduced left ventricular systolic function (left ventricular ejection fraction < or =40%) of 18%. In a receiver operating characteristic curve analysis, overall area under the curve (AUC) was 0.89. When looking at different age groups, AUC was highest (0.95) for <50 years, intermediate (0.90) for 50-75 years, and lowest (0.82) for >75 years. Using optimized decision limits, sensitivity, specificity, and negative predictive values (NPVs) were: <50 years (50 ng/L): 99.2, 57.2, and 99.7%; 50-75 years (75 ng/L): 95.9, 51.0, and 96.8%; and >75 years (250 ng/L): 87.9, 53.7, and 92.4%, respectively. Using only a single decision value (125 ng/L for all ages) gave sensitivities of 89.1, 91.9, and 94.3%; specificities of 84.0, 69.1, and 29.3% and NPVs of 97.7, 97.6, and 93.4%. A decision value of 400 ng/L for all ages gave much lower sensitivities. CONCLUSION: In a large population of patients in primary care, the use of age-stratified NT-proBNP decision limits considerably improves performance over current standards, with an excellent NPV for exclusion of reduced left ventricular systolic function.

Rosiglitazone reduces the development and rupture of experimental aortic aneurysms.

BACKGROUND: Development and rupture of aortic aneurysms involve a combination of complex biological processes. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, has been shown to have a broad spectrum of effects in vivo. The hypothesis that rosiglitazone would reduce aneurysm expansion or rupture was tested in the angiotensin II (Ang II)-induced hypercholesterolemic mouse model. METHODS AND RESULTS: Apolipoprotein E-deficient mice, 12 months of age, were allocated to 4 groups. Three groups were infused with Ang II (1 microg . min(-1) . kg(-1)), and the fourth was infused with saline. Rosiglitazone was given 1 week before infusion and 1 week after infusion. At day 28, aortic size was measured, and tissues were collected for analyses. Both pretreatment and posttreatment with rosiglitazone inhibited the occurrence of fatal rupture (11 of 30 versus 0 of 30 versus 0 of 15; P=0.0013) and reduced maximal dilatation of the aorta (4.6+/-0.13 versus 2.4+/-0.48 versus 2.15+/-0.46 mm2; P<0.0001). Blood glucose, total cholesterol, body weight, and atherosclerosis did not differ between groups. Pretreatment with rosiglitazone inhibited the Ang II-induced expression of angiotensin type 1a Ang II receptor while having no effect on the angiotensin type 2 Ang II receptor, in addition to reducing Ang II-induced expression of E-selectin, tumor necrosis factor-alpha, and interleukin-6. CONCLUSIONS: Pretreatment or posttreatment with RGZ reduced aortic expansion and rupture in this mouse model. Reduction of lesions in animals pretreated with rosiglitazone is concomitant with decreased expression of inflammatory mediators. Further studies are needed to elucidate the precise mechanism.

Clinical utility of cardiac troponin measurement in COVID-19 infection.

The novel coronavirus SARS-CoV-2 causes the disease COVID-19, a severe acute respiratory syndrome. COVID-19 is now a global pandemic and public health emergency due to rapid human-to-human transmission. The impact is far-reaching, with enforced social distancing and isolation, detrimental effects on individual physical activity and mental wellbeing, education in the young and economic impact to business. Whilst most COVID-19 patients demonstrate mild-to-moderate symptoms, those with severe disease progression are at a higher risk of mortality. As more is learnt about this novel disease, it is becoming evident that comorbid cardiovascular disease is associated with a greater severity and increased mortality. Many patients positive for COVID-19 demonstrate increased concentrations of cardiac troponin, creating confusion in clinical interpretation. While myocardial infarction is associated with acute infectious respiratory disease, the majority of COVID-19 patients demonstrate stable cTn rather than the dynamically changing values indicative of an acute coronary syndrome. Although full understanding of the mechanism of cTn release in COVID-19 is currently lacking, this mini-review assesses the limited published literature with a view to offering insight to pathophysiological mechanisms and reported treatment regimens.

False-positive troponin elevation due to an immunoglobulin-G-cardiac troponin T complex: a case report.

BACKGROUND: Troponin is a crucial biomarker for the diagnosis of an acute coronary syndrome (ACS). It rises in response to myocardial injury from significant acute myocardial ischaemia caused by obstructive coronary artery disease ['classical' myocardial infarction (MI)]. However, raised levels have also been noted in conditions not recognized as classical ACS. This may include MI with non-obstructed coronary arteries such as takotsubo cardiomyopathy and other acute or chronic conditions such as pulmonary embolus or chronic kidney disease. This is commonly labelled as a 'falsely elevated' troponin although there is some myocardial strain to explain the rise, such as an increase in cardiac oxygen demand. True 'falsely elevated' troponin, characterized by a persistent elevation in the absence of cardiac injury does occur and thought to be secondary to an immunoglobulin-troponin complex (macrotroponin). CASE SUMMARY: A 53-year-old gentleman with a background of diabetes, hypertension, hypercholesterolaemia, and hepatitis B was admitted with chest pain and persistently elevated cardiac troponin T (cTnT) levels. Investigations revealed unobstructed coronary arteries and a structurally normal, well-functioning heart. Subsequent biochemical analysis found the persistently elevated cTnT secondary to macrotroponin T. DISCUSSION: Macrotroponin, an immunoglobulin-troponin bound complex should be considered as a differential diagnosis when the biochemistry is not reflective of the clinical picture. Early recognition requires effective collaboration with the biochemistry laboratory for accurate diagnosis.

Left ventricular wall segment motion after ultra-endurance exercise in humans assessed by myocardial speckle tracking.

AIMS: Assessment of the left ventricular responses to prolonged exercise has been limited by technology available to assess cardiac tissue movement. Recently developed strain and strain rate imaging provide the unique opportunity to assess tissue deformation in all planes of motion. METHODS AND RESULTS: Nineteen runners (mean+/-SD age; 41+/-9 years) were assessed prior to and within 60 min (34+/-10 min) of race finish (Comrades Marathon, 89 km). Standard echocardiography assessed ejection fraction and the ratio of early to atrial (E/A) peak transmitral blood flow velocities. Myocardial speckle tracking determined segmental strain as well as systolic and diastolic strain rates in radial, circumferential, and longitudinal planes. Cardiac troponin T (cTnT) assessed cardiomyocyte insult. Ejection fraction (71+/-5 to 64+/-6%) and E/A (1.47+/-0.35 to 1.25+/-0.30) were reduced (P<0.05). Peak strain and peak systolic and diastolic strain rates were altered post-race in circumferential (e.g. peak strain reduced from 21.3+/-2.4 to 17.3+/-3.2%, P<0.05) and radial planes. Some individual heterogeneity was observed between segments and planes of motion. A post-race elevation in cTnT (range 0.013-0.272 microg/L) in 5/12 runners did not differentiate changes in LV function. CONCLUSION: Completion of the Comrades Marathon resulted in a depression in ejection fraction, E/A, as well as radial and circumferential strain and strain rates. Group data, however, masked some heterogeneity in cardiac function.

Cold water immersion improves recovery of sprint speed following a simulated tournament.

It is a common requirement in tournament scenarios for athletes to compete multiple times in a relatively short time period, with insufficient recovery time not allowing full restoration of physical performance. This study aimed to develop a greater understanding of the physiological stress experienced by athletes in a tournament scenario, and how a commonly used recovery strategy, cold water immersion (CWI), might influence these markers. Twenty-one trained male games players (age 19 ± 2; body mass 78.0 ± 8.8 kg) were randomised into a CWI group (n = 11) or a control group (n = 10). To simulate a tournament, participants completed the Loughborough Intermittent Shuttle Test (LIST) on three occasions in five days. Recovery was assessed at specific time points using markers of sprint performance, muscle function, muscle soreness and biochemical markers of damage (creatine kinase, CK), inflammation (IL-6 and C-Reactive Protein) and oxidative stress (lipid hydroperoxides and activity of 6 lipid-soluble antioxidants). The simulated tournament was associated with perturbations in some, but not all, markers of physiological stress and recovery. Cold water immersion was associated with improved recovery of sprint speed 24 h after the final LIST (ES = 0.83 ± 0.59; p = .034) and attenuated the efflux of CK pre- and post-LIST 3 (p < .01). The tournament scenario resulted in an escalation of physiological stress that, in the main, cold water immersion was ineffective at managing. These data suggest that CWI is not harmful, and provides limited benefits in attenuating the deleterious effects experienced during tournament scenarios.

Defective endovascular trophoblast invasion in the first trimester is associated with increased maternal serum ischemia-modified albumin.

BACKGROUND: Ischemia-modified albumin (IMA), a protein elevated in cardiac ischemia, is also increased to supra-physiological levels in early normal pregnancy. This finding supports the hypothesis that normal trophoblast development is stimulated by a hypoxic intrauterine environment. The aim of this study was to examine whether first trimester IMA levels are further elevated with defective trophoblast development. METHODS: Prospective study of healthy women with singleton pregnancies undergoing nuchal translucency assessment at 11-14 weeks. First trimester maternal serum IMA concentrations in those subsequently developing pre-term pre-eclampsia (n = 19) were compared to randomly chosen controls with normal pregnancy outcome (n = 69). RESULTS: Median first trimester serum IMA concentrations were significantly higher in women who subsequently developed pre-eclampsia (median 126.5 kU/L, interquartile range (IQR) 114.33-134.36 kU/L) when compared to those with normal pregnancy outcome (median 115.01 kU/L, IQR 102.29-124.81 kU/L, P = 0.02). CONCLUSIONS: Maternal serum IMA levels are elevated in the first trimester in women with pre-eclampsia, a clinical manifestation of defective endovascular trophoblast development. This suggests that abnormally high intrauterine hypoxia and subsequent reperfusion oxidative damage may be associated with defective trophoblast development. First trimester serum IMA may be a potential biomarker for abnormal placental development.