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Biomedical subjects

Paul Collinson

Publications and source records attributed to Paul Collinson.

17 recordsLinked to original sources

Accelerated Diagnostic Pathways for Suspected Acute Coronary Syndrome in Practice: A Randomized Trial of 0/1-Hour vs 0/3-Hour Troponin Testing.

BACKGROUND: For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS: This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS: From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS: Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/​1 Versus 0/​3 Hour Troponin Pathway [MACROS2]; NCT05322395).

Acute Coronary Syndrome↗

Novel application of flow propagation velocity and ischaemia-modified albumin in analysis of postexercise cardiac function in man.

The present study employed novel echocardiographic tools and cardiac markers to obtain a greater understanding of the aetiology and time course of altered cardiac function and cardiac damage following prolonged exercise and, in particular, the possible role of transient ischaemia within these phenomena. Fourteen runners in the 2004 London Marathon were assessed pre-, immediately post-, 1 h post- and 24 h postcompletion of the race. Left ventricular function was examined echocardiographically using 2-D, M-mode, tissue Doppler imaging and flow propagation velocity (Vp). Venous blood samples were analysed for N-terminal pro-B-type natriuretic peptide (proBNP), cardiac troponin T (cTnT) and ischaemia-modified albumin (IMA). Left ventricular (LV) diastolic filling was altered on completion of the race, as indicated by significant decreases in mean early to late diastolic myocardial wave (E':A') ratio and Vp (from 1.82 +/- 0.9 to 1.32 +/- 0.32, and from 67.5 +/- 9.3 to 60.2 +/- 8.2 cm s(-1), respectively, P < 0.05), accompanied by an increase in proBNP (from 21.6 +/- 11 to 47.08 +/- 19.5 pg l(-1), P < 0.05). The observed reduction in LV diastolic filling following completion of a marathon, unrelated to changes in heart rate or loading parameters, indicates an intrinsically mediated change in diastolic filling. Exercise-induced elevations in cTnT in nine individuals (range, 0.023-0.37 microg l(-1)) were indicative of minor cardiac damage. A significant reduction in IMA was observed after the marathon (from 63.68 +/- 9.83 to 44.94 +/- 16.13 Um l(-1), P < 0.05), unrelated to the alterations in cardiac function, proBNP or cTnT. The absence of an elevation in IMA suggests that exercise-induced myocardial ischaemia did not occur and therefore could not explain the changes in cardiac function or biomarkers. Future studies in this area should investigate alternative diagnostic tools for the detection of transient ischaemia, and other potential mechanisms, in order to extend the understanding of this phenomenon.

Adult↗

Ischemia-modified albumin concentrations should be interpreted with caution in patients with low serum albumin concentrations.

OBJECTIVE: Ischemia-modified albumin (IMA((R))) is a novel marker for assessing cardiac ischaemia. We assessed the relationship between total albumin concentrations and IMA in serum to investigate whether interpretation of IMA was albumin-dependent. SUBJECTS AND METHODS: 298 serum samples were assayed for total albumin (albumin), using bromcresol purple, and IMA, using an indirect colorimetric assay. Correlations were investigated for the whole data set and for two subgroups, those samples with low albumin (< or =34 g/l) and those with albumin within the reference interval. RESULTS: There was a significant (r = -0.888, p < 0.0001) negative correlation between IMA and albumin both over the entire range of albumin concentrations and in the low albumin concentration subgroup (r = -0.85, p < 0.0001); however, there was less significant correlation in the subgroup with albumin within the reference interval (r = -0.37, p < 0.0001). CONCLUSION: A negative correlation exists between IMA and albumin concentrations; however, there is less significant correlation when albumin is within the reference interval. IMA concentrations determined in patients with albumin concentrations < or =34 g/l should be interpreted with some caution.

Adolescent↗

Plasma DNA concentration as a predictor of mortality and sepsis in critically ill patients.

INTRODUCTION: Risk stratification of severely ill patients remains problematic, resulting in increased interest in potential circulating markers, such as cytokines, procalcitonin and brain natriuretic peptide. Recent reports have indicated the usefulness of plasma DNA as a prognostic marker in various disease states such as trauma, myocardial infarction and stroke. The present study assesses the significance of raised levels of plasma DNA on admission to the intensive care unit (ICU) in terms of its ability to predict disease severity or prognosis. METHODS: Fifty-two consecutive patients were studied in a general ICU. Blood samples were taken on admission and were stored for further analysis. Plasma DNA levels were estimated by a PCR method using primers for the human beta-haemoglobin gene. RESULTS: Sixteen of the 52 patients investigated died within 3 months of sampling. Nineteen of the 52 patients developed either severe sepsis or septic shock. Plasma DNA was higher in ICU patients than in healthy controls and was also higher in patients who developed sepsis (192 (65-362) ng/ml versus 74 (46-156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185-430) ng/ml versus 71 (46-113) ng/ml, P < 0.001) or in hospital (260 (151-380) ng/ml versus 68 (47-103) ng/ml, P < 0.001). Plasma DNA concentrations were found to be significantly higher in patients who died in the ICU. Multiple logistic regression analysis determined plasma DNA to be an independent predictor of mortality (odds ratio, 1.002 (95% confidence interval, 1.0-1.004), P = 0.05). Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration higher than 127 ng/ml was taken as a predictor for death on the ICU. CONCLUSION: Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive care patients.

Adult↗

What is the most cost-effective strategy to screen for left ventricular systolic dysfunction: natriuretic peptides, the electrocardiogram, hand-held echocardiography, traditional echocardiography, or their combination?

AIMS: To assess the screening characteristics and cost-effectiveness of screening for left ventricular systolic dysfunction (LVSD) in community subjects. METHODS AND RESULTS: A total of 1392 members of the general public and 928 higher risk subjects were randomly selected from seven community practices. Attending subjects underwent an ECG, N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels, and traditional echocardiography (TE). A total of 533 consecutive subjects underwent hand-held echocardiography (HE). The screening characteristics and cost-effectiveness (cost per case of LVSD diagnosed) of eight strategies to predict LVSD (LVSD <45% on TE) were compared. A total of 1205 subjects attended. Ninety six per cent of subjects with LVSD in the general population had identifiable risk factors. All screening strategies gave excellent negative predictive value. Screening high-risk subjects was most cost-effective, screening low-risk subjects least cost-effective. TE screening was the least cost-effective strategy. NTproBNP screening gave similar cost savings to ECG screening; HE screening greater cost-savings, and HE screening following NTproBNP or ECG pre-screening the greatest cost-savings, costing approximately 650 Euros per case of LVSD diagnosed in high-risk subjects (63% cost-savings vs.TE). CONCLUSION: Thus several different modalities allow cost-effective community-based screening for LVSD, especially in high-risk subjects. Such programmes would be cost-effective and miss few cases of LVSD in the community.

Adolescent↗

What is the normal range for N-terminal pro-brain natriuretic peptide? How well does this normal range screen for cardiovascular disease?

AIMS: To define the N-terminal pro-brain natriuretic peptide (NTpBNP) normal range, assessing its cardiovascular screening characteristics in general population and higher risk subjects. METHODS AND RESULTS: A total of 2320 subjects (1392 general population and 928 high-risk) > or =45 years old, selected randomly from seven community practices, were invited to undergo clinical assessment and echocardiography and to assess NTpBNP serum levels. Of these, 1205 attended. The NTpBNP normal range was calculated and its cardiovascular screening characteristics were assessed. Age (P<0.0001) and female gender (P<0.0001) independently predicted NTpBNP levels in normal subjects. In the general population, age- and gender-stratified normal NTpBNP levels gave a negative-predictive value (NPV) of 99% in excluding left ventricular systolic dysfunction, atrial fibrillation, and valvular heart disease, and a positive predictive value of 56% in detecting any cardiovascular disease assessed. In high-risk subjects, these values were 98 and 62%, respectively. Ninety-five per cent of subjects with NTpBNP levels over four times the normal had significant cardiovascular disease with the others having renal dysfunction. CONCLUSION: Normal NTpBNP levels should be stratified by age and gender. Normal NTpBNP levels give high NPV in excluding significant cardiovascular disease. Most subjects with raised NTpBNP levels and almost all subjects with NTpBNP levels over four times the normal have significant cardiovascular disease.

Age Distribution↗

Cardiac troponins in intensive care.

The cardiac troponins are integral components of the myofibrillary apparatus and they regulate muscle contraction. The measurement of cardiac troponins has replaced other biomarkers for the specific detection of myocardial necrosis and for the diagnosis of myocardial infarction. The tissue specificity plus sensitivity of the measurement technology has meant that cardiac damage can be detected in circumstances other than conventional acute coronary syndromes. The ability to specifically detect cardiac damage as part of multiple organ failure in intensive care patients has been shown to provide prognostic information, but it is unclear whether this is a dependent or an independent marker of outcome.

Biomarkers↗

Effect of radiofrequency catheter ablation on the biochemical marker ischemia modified albumin.

Ischemia-modified albumin (IMA) levels were measured after radiofrequency (RF) catheter ablation to evaluate the effect of direct myocardial necrosis on IMA formation. IMA levels have been shown to increase in patients after RF catheter ablation compared with those who undergo diagnostic electrophysiologic studies. The results of this study suggest that IMA may be a marker of myocardial injury.

Adult↗

Ischemia Modified Albumin for the assessment of patients presenting to the emergency department with acute chest pain but normal or non-diagnostic 12-lead electrocardiograms and negative cardiac troponin T.

BACKGROUND: The diagnosis of myocardial ischemia in patients with acute chest pain at rest but non-diagnostic electrocardiograms (ECG) is problematic. Ischemia Modified Albumin (IMA) is a new biochemical marker of ischemia, which may be useful to characterise acute coronary syndrome (ACS) patients. METHODS: We studied 131 patients (mean age 58.5 years; 95 male) presenting to the emergency department with symptoms suggestive of ACS but with normal or non-diagnostic ECGs. Cardiac troponin T (cTnT) and IMA were measured within 3 h of last chest pain episode. Based on hospital diagnostic test results, patients were classified as having ACS or non-ischemic chest pain (NICP), by two independent cardiologists unaware of IMA results. RESULTS: Mean IMA levels (U/ml) were higher in patients with ACS (98.3+/-11) compared to patients with NICP (85.5+/-15); p<0.0001. IMA levels >93.5 U/ml demonstrated a sensitivity and specificity of 75% for the diagnosis of ACS; area under the receiver operator characteristic curve 0.78 (95% CI: 0.70-0.85). If we applied the manufacturer cutoff point of 85 U/ml, the sensitivity of IMA increased to 90.6% with a specificity of 49.3% (negative predictive value=84.6%). In combination with cTnT (6-12 h) (>0.05 ng/ml), the sensitivity increased to 92.2%. After multivariate analysis, IMA levels >85 U/ml (odds ratio=14.6 [95% CI 4.4-48.4]; p<0.0001), age and prior myocardial infarction were independent predictors of ACS. CONCLUSION: IMA may be a useful biomarker for the identification of ACS in patients presenting with typical acute chest pain but normal or non-diagnostic ECGs.

Adult↗

Altered cardiac function and minimal cardiac damage during prolonged exercise.

PURPOSE: The purpose of the present study was to examine markers of cardiac function and cardiac damage during a simulated half-ironman triathlon in highly trained athletes. METHODS: Nine highly trained male triathletes volunteered for the study (mean +/- SD; age: 33 +/- 3 yr; height: 1.8 +/- 0.1 m; body mass: 77.7 +/- 3.2 kg). The subjects completed a half-ironman triathlon; 1.9-km swim in an indoor 20-m pool, followed by a laboratory-based 90-km cycle and 21.1-km run. Venous blood samples were drawn and echocardiographic assessment completed before the start of exercise, immediately after each stage, and 24 h postexercise. Serum was analyzed for total creatine kinase activity (CK), creatine kinase isoenzyme MB(mass) (CK-MB(mass)), and cardiac troponin T (cTnT). Left ventricular systolic (stroke volume, and systolic blood pressure/end systolic volume ratio (SBP/ESV)) and diastolic (ratio of early [E] to late [A], ventricular filling E:A) measurements were derived from echocardiographic assessment. RESULTS: The mean completion time of the half-ironman triathlon was 301 +/- 28 min. Left ventricular contractility (SBP/ESV) was significantly reduced after the half-ironman triathlon (P < 0.05). A significant reduction in E:A was observed after the run phase of the half-ironman triathlon (P < 0.05). Significant increases in CK and CK-MB(mass) were observed during and after the half-ironman triathlon (P < 0.05), and cTnT was elevated in four subjects over the course of the half-ironman triathlon. CONCLUSIONS: The physiologic stress imposed by the half-ironman triathlon resulted in a reduced left ventricular contractility and altered diastolic filling, coupled with minimal cardiac damage in a number of highly trained male triathletes. The mechanisms behind such altered cardiac function and cardiac damage after prolonged exercise are yet to be elucidated.

Adult↗

The impact of prolonged exercise in a cold environment upon cardiac function.

PURPOSE: The purpose of the present study was to examine the impact of cold exposure coupled with prolonged exercise upon postexercise left ventricular (LV) function and markers of myocardial damage. METHODS: colon; Eight highly trained male athletes (mean +/- SD; age: 28.2 +/- 8.8 yr; height: 1.78 +/- 0.07 m; body mass: 74.9 +/- 7.6 kg; VO2max: 65.6 +/- 7.0 mL x kg(-1) x min(-1)) performed two 100-mile cycle trials, the first in an ambient temperature of 0 degrees C, the second in an ambient temperature of 19 degrees C. Echocardiographic assessment was completed and blood samples drawn before, immediately postexercise, and 24-h postexercise. Left ventricular systolic (stroke volume [SV], ejection fraction [EF], and systolic blood pressure/end systolic volume ratio [SBP/ESV]) and diastolic (early [E] to late [A] filling ratio [E:A]) parameters were calculated. Serum was analyzed for creatine kinase isoenzyme MB (CK-MBmass) and cardiac troponin T (cTnT). cTnT was analyzed descriptively whereas other variables were assessed using two-way repeated-measures ANOVA. RESULTS: No significant change was observed in systolic function across time or between trials. A significant difference between trials was observed in E:A immediately after exercise (1.4 +/- 0.4 [19 degrees C] vs 1.8 +/- 0.3 [0 degrees C]) (P < 0.05). CK-MBmass was significantly elevated immediately after exercise in both trials (P < 0.05). Positive cTnT concentrations were observed in two subjects immediately after the 19 degrees C trial (0.012 microg x L(-1) and 0.034 microg x L(-1)). CONCLUSIONS: Cycling 100 miles in an ambient temperature of 19 degrees C is associated with an acute change in diastolic filling that is not observed after prolonged exercise at 0 degrees C. Prolonged exercise is associated with minimal cardiac damage in some individuals; it appears that this is a separate phenomenon to the change in diastolic filling.

Adult↗

Postexercise left ventricular function and cTnT in recreational marathon runners.

PURPOSE: To assess the impact of prolonged exercise on left ventricular (LV) function and the appearance of cardiac troponin T (cTnT) in older and recreational athletes. METHODS: Heart rate (HR), blood pressures, and cTnT were recorded in 35 subjects (age range 22-57 yr, finishing time 157-341 min) pre- and postrace. Echocardiograms (N = 26) assessed stroke volume (SV), ejection fraction (EF), sBP/LV end-systolic volume (sBP/ESV), diastolic filling (E:A ratio) as well as preload (LV internal dimension at end-diastole [LVIDd]) and afterload (LV wall stress). HR and core temperature were recorded in-event. Prepost changes in LV function were analyzed by repeated measures t-test. Delta scores for LV function and cTnT data were correlated with each other, age, finishing time, alterations in loading, and in-event data. RESULTS: SV was significantly decreased postrace (109 +/- 31 vs 85 +/- 25 mL, P < 0.05) likely due to a significant decrease in LVIDd (5.3 +/- 0.4 vs 4.9 +/- 0.5 cm, P < 0.05; r = 0.80, P < 0.05). LV wall stress was unchanged postrace (90 +/- 25 vs 89 +/- 27 g x cm(-2), P > 0.05). EF (70 +/- 12 vs.70 +/- 10%, P > 0.05) and sBP/ESV (3.7 +/- 2.9 vs 4.0 +/- 2.0, P > 0.05) did not change prepost race and were not related to age or finishing time (P > 0.05). E:A ratio was significantly reduced postrace (1.73 +/- 0.38 vs 1.41 +/- 0.25, P < 0.05) and could not be explained by an increased HR (56 +/- 9 vs 84 +/- 10, P < 0.05; r = 0.08, P > 0.05), a reduced LVIDd (r = 0.11, P > 0.05), age, finishing time, or in-event data. Postrace 26/33 subjects presented cTnT values in the range 0.024-0.080 microg x L(-1) that were not related to changes in LV function, loading, age, finishing time, or in-event data. CONCLUSION: No evidence of load-independent depression in LV systolic function was reported. Changes in cTnT and E:A were not related, and their etiology is uncertain.

Adult↗

Independent value of tissue harmonic echocardiography for risk stratification in patients with non-ST-segment elevation acute chest pain.

BACKGROUND: Clinical factors, electrocardiography, and cardiac troponins provide a satisfactory, although not ideal, means for risk-stratifying patients with non-ST-segment elevation acute chest pain. Tissue harmonic echocardiography enables improved assessment of wall motion abnormalities compared with fundamental echocardiography and may be a useful adjunct for the detection of myocardial ischemia and infarction. We aimed to determine the value of tissue harmonic echocardiography in relation to electrocardiographic and biochemical factors for risk stratification of these patients. RESULTS: Eighty patients with non-ST-segment elevation chest pain were studied using tissue harmonic echocardiography and troponin-T and -I. Fifty-five (69%) patients had abnormal electrocardiograms and 47 (59%) patients had abnormal echocardiograms. Thirteen patients (17%) had elevated troponin-T levels and 17 (21%) had elevated levels of troponin-I. Twelve patients (15%) had a myocardial infarction as the presenting event and, of the remaining 68 patients, 24 sustained an adverse cardiac event during the follow-up period (3 cardiac deaths, 4 nonfatal myocardial infarctions, 17 revascularization procedures). Troponin-T (98%), troponin-I (97%), and echocardiography (97%) all had similar negative predictive values for myocardial infarction as the presenting event, but troponin-T was the only independent predictor of this endpoint (relative risk 230, 95% CI 22-2427). An abnormal echocardiogram was the only independent predictor of subsequent events. The independent predictors of all events were age, troponin-T, and echocardiography. CONCLUSION: Tissue harmonic echocardiography provides independent information for risk stratification of patients with non-ST-segment elevation acute chest pain.

Aged↗

The cardiospecificity of the third-generation cTnT assay after exercise-induced muscle damage.

PURPOSE: The purpose of the present study was to examine the cardiospecificity of cTnI and the new third-generation cTnT assay, in the presence of exercise-induced muscle damage in highly trained individuals, and to examine the impact of a maximal-ramping treadmill test on cardiac function. METHODS: Eight highly trained male triathletes (mean +/- SD; age: 29 +/- 9 yr; height: 1.79 +/- 0.10 m; body mass: 77 +/- 10 kg; .VO(2max): 67.4 +/- 6.3 mL.kg(-1).min(-1)) completed two bouts of exercise. On the first occasion, subjects completed a maximal-ramping treadmill test. On a separate occasion, the subjects completed 30 min of downhill running (15% gradient) at a speed equivalent to 70% of maximal running velocity attained during the maximal-ramping treadmill test. All subjects were assessed using ECG, echocardiography, and blood analysis. Measurements were taken at rest, immediately after, and 48 h postexercise for each bout of exercise. Echocardiographic analysis was used to determine left ventricular systolic and diastolic function. Blood samples were analyzed for markers of myocyte damage. RESULTS: Echocardiographic results indicated normal left ventricular function before and after both exercise bouts. Total CK and CKMB were significantly elevated 48 h after the downhill run. cTnT and cTnI were not elevated at any stage of the study. CONCLUSIONS: Neither the maximal-ramping treadmill test nor the 30-min downhill run produced cardiac dysfunction or myocardial damage in young, healthy trained subjects. The elevated total CK and CKMB within the downhill study are noncardiac in origin as demonstrated by the lack of cTnT and cTnI. The cTnI and new third-generation cTnT assays may be used to detect cardiac damage in the presence of elevated total CK and CKMB associated with exercise-induced skeletal muscle damage.

Adult↗

Rapid assessment of patients with non-ST-segment elevation acute chest pain: troponins, inflammatory markers, or perfusion imaging?

BACKGROUND: Perfusion imaging during or soon after pain has been shown to provide diagnostic and prognostic information in patients with suspected angina. Measurement of troponin I (TnI) and troponin T (TnT) provides similar information but only several hours after onset of pain. The role of inflammatory markers in this setting is less clear. METHODS AND RESULTS: We prospectively studied 80 nonconsecutive patients using gated technetium 99m sestamibi single photon emission computed tomography (MIBI), TnT, TnI, C-reactive protein, IL-6, and tumor necrosis factor alpha. Of these patients, 50 (63%) had abnormal MIBI, 13 (17%) had elevated TnT, 17 (21%) had elevated TnI, and C-reactive protein, IL-6, and tumor necrosis factor alpha were raised in 46 (58%), 14 (18%), and 29 (37%), respectively. Myocardial infarction was the presenting event in 13 patients (16%), and 23 (34%) of those without index myocardial infarction sustained a cardiovascular event during follow-up. MIBI, TnT, TnI, and electrocardiogram all had similar negative predictive values for index myocardial infarction (97%, 97%, 95%, and 97%, respectively). However, only MIBI had a high negative predictive value for the prediction of subsequent events during follow-up (86%). TnT and MIBI were the only independent predictors of all events. Inflammatory markers provided no useful additional prognostic information. CONCLUSIONS: The combination of TnT and MIBI is the best model for early prediction of cardiac events in patients with acute chest pain.

Acute Disease↗