David Gaze

Role of "Ischemia modified albumin", a new biochemical marker of myocardial ischaemia, in the early diagnosis of acute coronary syndromes.

Background: Diagnosis of cardiac ischaemia in patients attending emergency departments (ED) with symptoms of acute coronary syndromes is often difficult. Cardiac troponin (cTn) is sensitive and specific for the detection of myocardial damage but may not rise during reversible myocardial ischaemia. Ischemia Modified Albumin (IMA) has recently been shown to be a sensitive and early biochemical marker of ischaemia. Methods and Results: This study evaluated IMA in conjunction with ECG and cTn in 208 patients presenting to the ED within three hours of acute chest pain. At presentation, a 12-lead ECG was recorded and blood taken for IMA and cardiac troponin T (cTnT). Patients underwent standardised triage, diagnostic procedures, and treatment. Results of IMA, ECG, and cTnT, alone and in combination, were correlated with final diagnoses of non-ischaemic chest pain, unstable angina, ST segment elevation, and non-ST segment elevation myocardial infarction. In the whole patient group, sensitivity of IMA at presentation for an ischaemic origin of chest pain was 82%, compared with 45% of ECG and 20% of cTnT. IMA used together with cTnT or ECG, had a sensitivity of 90% and 92%, respectively. All three tests combined identified 95% of patients whose chest pain was attributable to ischaemic heart disease. In patients with unstable angina, sensitivity of IMA used alone was equivalent to that of IMA and ECG combined. Conclusions: IMA is highly sensitive for the diagnosis of myocardial ischaemia in patients presenting with symptoms of acute chest pain.

Exercise-Induced Cardiac Troponin Elevation Evidence, Mechanisms, and Implications

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations.

Ischemia Modified Albumin Is a Sensitive Marker of Myocardial Ischemia After Percutaneous Coronary Intervention

Background—Ischemia modified albumin (IMA; Ischemia Technologies, Inc) blood levels rise in patients who develop ischemia during percutaneous coronary intervention (PCI). It is not known whether IMA elevations correlate with increases in other markers of oxidative stress, ie, 8-iso prostaglandin F2-A (iP). Methods and Results—We compared IMA versus iP plasma levels in 19 patients (mean age 62.8±11.9 years) undergoing PCI and 11 patients (mean age 64±13.6 years) undergoing diagnostic angiography (controls). In the PCI patients, blood samples for IMA and iP were taken from the guide catheter before PCI and after balloon inflations, and from the femoral sheath 30 minutes after PCI. IMA was measured by the albumin cobalt binding (ACB) test and plasma iP by enzyme immunoassay. During PCI, all 19 patients had chest pain and 18 had transient ischemic ST segment changes. IMA was elevated from baseline in 18 of the 19 patients after PCI. Median IMA levels were higher after PCI (101.4 U/mL, 95%CI 82 to 116) compared with baseline (72.8 U/mL, CI 55 to 93;P <0.0001). Levels remained elevated at 30 minutes (87.9 U/mL, CI 78 to 99;P <0.0001) and returned to baseline at 12 hours (70.3 U/mL, CI 65 to 87;P =0.65). iP levels were raised after PCI in 9 of the 19 patients. However, median iP levels were not significantly different immediately (P =0.6) or 30 minutes after PCI (P =0.1). In the control group, IMA and iP levels remained unchanged before and after angiography (P =0.2 and 0.16, respectively). Conclusions—IMA is a more consistent marker of ischemia than iP in patients who develop chest pain and ST segment changes during PCI.

State-of-the-Art PaperExercise-Induced Cardiac Troponin Elevation: Evidence, Mechanisms, and Implications

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations.

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.

Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys™ 1010 and 2010 analysers

The Elecsys NT‐proBNP assay is based on two polyclonal antibodies directed at residues 1–21 and 39–50 of the NT‐proBNP molecule. Analytical performance was assessed using NCCLS protocol EP‐5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7–1.6 (1010) and 1.2–1.5 (2010) and between run CV 5.3–6.7 (1010) and 4.4–5.0 (2010). In the multicentre evaluation within run CV was 1.0–2.5% with total imprecision 1.5–2.5% and between labs imprecision 3.8–4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x−0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 °C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT‐proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT‐proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT‐proBNP values increased with age and were higher in women than men.

Cardiac Troponin T Release Is Stimulated by Endurance Exercise in Healthy Humans

To the Editor: Post-exercise release of cardiac troponin (cTn)T and cTnI has been previously reported after prolonged bouts of exercise ([1][1]). However, this release has only been observed in a limited number of subjects ([2][2]). It is unclear whether post-exercise release of cTn represents

Changes in vascular and cardiac function after prolonged strenuous exercise in humans

Prolonged exercise has been shown to result in an acute depression in cardiac function. However, little is known about the effect of this type of exercise on vascular function. Therefore, the purpose of the present study was to investigate the impact of an acute bout of prolonged strenuous exercise on vascular and cardiac function and the appearance of biomarkers of cardiomyocyte damage in 15 male (32 +/- 10 yr) nonelite runners. The subjects were tested on two occasions, the day before and within an hour of finishing the London marathon (229 +/- 38 min). Function of the brachial and femoral arteries was determined using flow-mediated dilatation (FMD). Echocardiographic assessment of cardiac strain, strain rate, tissue velocities, and flow velocities during diastole and systole were also obtained. Venous blood samples were taken for later assessment of cardiac troponin I (cTnI), a biomarker of cardiomyocyte damage. Completion of the marathon resulted in a depression in femoral (P = 0.04), but not brachial (P = 0.96), artery FMD. There was no change, pre- vs. postmarathon, in vascular shear, indicating that the impaired femoral artery function was not related to hemodynamic changes. The ratio of peak early to atrial radial strain rate, a measure of left ventricular diastolic function, was reduced postmarathon (P = 0.006). Postrace cTnI was elevated in 12 of 13 runners, with levels above the recognized clinical threshold for damage in 7 of these. In conclusion, when taken together, these data suggest a transient depression in cardiac and leg vascular function following prolonged intensive exercise.

Mitral annular myocardial velocity assessment of segmental left ventricular diastolic function after prolonged exercise in humans

We assessed segmental and global left ventricular (LV) diastolic function via tissue‐Doppler imaging (TDI) as well as Doppler flow variables before and after a marathon race to extend our knowledge of exercise‐induced changes in cardiac function. Twenty‐nine subjects (age 18–62 year) volunteered to participate and were assessed pre‐ and post‐race. Measurements of longitudinal plane TDI myocardial diastolic velocities at five sites on the mitral annulus included peak early myocardial tissue velocity (E′), peak late (or atrial) myocardial tissue velocity (A′) and the ratio E′/A′. Standard pulsed‐wave Doppler transmitral and pulmonary vein flow indices were also recorded along with measurements of body mass, heart rate, blood pressures and cardiac troponin T (cTnT), a biomarker of myocyte damage. Pre‐ to post‐race changes in LV diastolic function were analysed by repeated measures ANOVA. Delta scores for LV diastolic function were correlated with each other and alterations in indices of LV loading. Diastolic longitudinal segmental and mean TDI data were altered post‐race such that the mean E′/A′ ratio was significantly depressed (1.51 ± 0.34 to 1.16 ± 0.35, P < 0.05). Changes in segmental and global TDI data were not related to an elevated post‐race HR, a decreased post‐race pre‐load or an elevated cTnT. The pulsed wave Doppler ratio of peak early transmitral flow velocity (E)/peak late (or atrial) flow velocity (A) was also significantly reduced post‐race (1.75 ± 0.46 to 1.05 ± 0.30, P < 0.05); however, it was significantly correlated with post‐race changes in heart rate. The lack of change in E/E′ from pre‐ to post‐race (3.4 ± 0.8 and 3.3 ± 0.7, respectively) suggests that the depression in diastolic function is likely to be due to altered relaxation of the left ventricle; however, the exact aetiology of this change remains to be determined.

Impact of marathon running on cardiac structure and function in recreational runners

The present study examined the relationship between LV (left ventricular) function, markers of cardiac-specific damage and markers of oxidative stress in recreational runners following a marathon. Runners (n=52; 43 male and nine female; age, 35+/-10 years; height, 1.74+/-0.08 m; body mass, 75.9+/-8.9 kg) were assessed pre- and immediately post-marathon. LV function was assessed using standard M-mode two-dimensional Doppler echocardiography and TDI (tissue-Doppler imaging) echocardiography. Serum was analysed for cTnT (cardiac troponin-T), TEAC (Trolox equivalent antioxidant capacity; a measure of total antioxidant capacity), MDA (malondealdehyde) and 4-HNE (4-hydroxynonenal). A strong relationship was observed between standard and TDI echocardiography for all functional measures. Diastolic function was altered post-marathon characterized by a reduction in E (peak early diastolic filling: 0.79+/-0.11 compared with 0.64+/-0.16 cm/s; P<0.001), an increase in A (peak late diastolic filling: 0.48+/-0.11 compared with 0.60+/-0.12 cm/s; P<0.001) and a resultant decrease in E/A (ratio of E to A; 1.71+/-0.48 compared with 1.10+/-0.31; P<0.001). Ejection fraction remained unchanged post-marathon. Thirty-two runners presented with cTnT values above the lower limit of detection for the assay (0.01 microg/l), and 20 runners presented post-marathon with cTnT values above the acute myocardial infarction cut-off value (0.05 microg/l). No significant correlations were observed between cTnT and any functional measurements. MDA (2.90+/-1.58 compared with 3.59+/-1.47 micromol/l) and TEAC (1.80+/-0.12 compared with 1.89+/-0.21 mmol/l) were significantly increased post-marathon, but were unrelated to changes in function or cTnT. In conclusion, the present study demonstrated a reduction in diastolic function and widespread evidence of minimal cardiac damage following a marathon in recreational runners. The mechanism(s) underpinning the altered function and appearance of cTnT appear unrelated to reactive oxygen species.