Johannes Mair

Cross-Reactivity of BNP, NT-proBNP, and proBNP in Commercial BNP and NT-proBNP Assays: Preliminary Observations from the IFCC Committee for Standardization of Markers of Cardiac Damage

B-type natriuretic peptide (BNP) is a 32 amino acid cardiac-synthesized hormone that reduces blood pressure and increases sodium excretion (1). Following proteolytic cleavage of proBNP, a 108-amino acid precursor, an N-terminal fragment (NT-proBNP) and BNP are released (2). Increased concentrations of BNP and NT-proBNP can be used clinically to monitor heart failure, but a lack of alignment between commercial BNP and NT-proBNP assays (3) can lead to confusion when clinicians or laboratorians compare results measured for the same analyte on different instruments. Some of this confusion arises from variable assay specificity regarding what peptides are being measured. We studied whether ( a ) BNP assays demonstrated cross-reactivity with NT-proBNP or proBNP, and ( b ) whether NT-proBNP assays demonstrated cross-reactivity with BNP or proBNP, by using 5 commercial BNP and 3 commercial NT-proBNP assays with 2 BNP, 2 NT-proBNP, and 2 proBNP materials. The NPs studied were: Peptide Institute synthetic BNP (aa 77–108), Scios human recombinant BNP (aa 77–108), HyTest human recombinant NT-proBNP (aa 1–76), Roche modified (amidated for stabilization) synthetic NT-proBNP, HyTest human recombinant proBNP (aa 1–108), and Scios glycosylated human recombinant proBNP. BNP assays evaluated were Abbott Architect, Abbott AxSYM, Bayer …

Predictive value of NT-pro BNP after acute myocardial infarction: Relation with acute and chronic infarct size and myocardial function

AIM OF THE STUDY We sought to assess the relation of N-terminal brain natriuretic peptide (NT-pro BNP) determined on day 3 after onset of acute myocardial infarction (AMI) symptoms with acute and chronic infarct size and functional parameters assessed by cardiac magnetic resonance (CMR) imaging. Furthermore, we wanted to investigate its predictive value for recovery of myocardial function. METHODS CMR was performed in 49 consecutive patients within 6 days and in a subgroup 4 (n = 27) and 12 (n = 22) months after first acute ST-elevation AMI and successful primary angioplasty. NT-pro BNP was measured in the subacute phase at 66 ± 8 h after onset of symptoms. RESULTS Log-transformed NT-pro BNP (lgNT-pro BNP) significantly correlated with infarct size in % of left ventricular myocardial mass (r = 0.59 to 0.64; p < 0.004), with ejection fraction (EF) (r = -0.49 to -0.55; p < 0.004) as well as with segmental wall thickening (SWT, mm) (r = 0.41 to -0.52; p < 0.04) at any time of assessment. Multiple linear regression analysis revealed baseline EF and lgNT-pro BNP to predict global functional recovery. Patients with NT-pro BNP concentrations 1115 pg/ml did not show significant functional recovery (all p = NS). CONCLUSION NT-pro BNP on day 3 after admission correlates with acute and chronic infarct size and myocardial function after AMI. Global and regional myocardial function did not recover in patients with higher NT-pro BNP (>1115 pg/ml) during subacute phase of AMI.

Cardiac troponin: a critical review of the case for point-of-care testing in the ED

The measurement of cardiac troponin concentrations in the blood is a key element in the evaluation of patients with suspected acute coronary syndromes, according to current guidelines, and contributes importantly to the ruling in or ruling out of acute myocardial infarction. The introduction of point-of-care testing for cardiac troponin has the potential to reduce turnaround time for assay results, compared with central laboratory testing, optimizing resource use. Although, in general, many point-of-care cardiac troponin tests are less sensitive than cardiac troponin tests developed for central laboratory-automated analyzers, point-of-care systems have been used successfully within accelerated protocols for the reliable ruling out of acute coronary syndromes, without increasing subsequent readmission rates for this condition. The impact of shortened assay turnaround times with point-of-care technology on length of stay in the emergency department has been limited to date, with most randomized evaluations of this technology having demonstrated little or no reduction in this outcome parameter. Accordingly, the point-of-care approach has not been shown to be cost-effective relative to central laboratory testing. Modeling studies suggest, however, that reengineering overall procedures within the emergency department setting, to take full advantage of reduced therapeutic turnaround time, has the potential to improve the flow of patients through the emergency department, to shorten discharge times, and to reduce cost. To properly evaluate the potential contribution of point-of-care technology in the emergency department, including its cost-effectiveness, future evaluations of point-of-care platforms will need to be embedded completely within a local decision-making structure designed for its use.

Glycogen phosphorylase isoenzyme BB to diagnose ischaemic myocardial damage

Glycogen phosphorylase isoenzyme BB (GPBB) is a key enzyme of glycogenolysis. Its degree of association with the sarcoplasmatic reticulum glycogenolysis complex depends essentially on the metabolic state of the myocardium. With the onset of tissue hypoxia, when glycogen is broken down, GPBB is converted from a structurally bound into a cytoplasmatic form. Considerable amounts of GPBB are only found in human heart and brain. In the first clinical studies GPBB was the most sensitive marker for the diagnosis of acute myocardial infarction within 4 h of chest pain onset. GPBB also increases early in patients with unstable angina and reversible ST-T alterations in the resting electrocardiogram at hospital admission, which could be useful for risk stratification. GPBB is sensitive for the detection of perioperative ischaemic myocardial damage and infarction in patients undergoing coronary artery bypass grafting. The diagnostic specificity of GPBB in non-traumatic chest pain patients was comparable to creatine kinase MB. These results indicate that GPBB is a sensitive marker for ischaemic myocardial damage.

Association of copeptin with myocardial infarct size and myocardial function after ST segment elevation myocardial infarction

Objective To investigate the relationship between circulating plasma copeptin values and infarct size as well as myocardial function at baseline and 4 months after mechanical reperfusion for ST segment elevation myocardial infarction (STEMI). Design Prospective observational cohort study. Setting University Hospital of Innsbruck. Patients 54 patients with acute STEMI. Main outcome measures Correlation of plasma copeptin with infarct size as well as left ventricular ejection fraction (LVEF) and remodelling. Methods Participants underwent contrast enhanced cardiac MRI at baseline and 4 months thereafter. Blood samples were drawn 2 days after the onset of symptoms. Copeptin values were determined by an immunofluorescent assay. Results Copeptin concentrations (median 10.4 pmol/l, IQR 6.0–14.4) were associated with early and chronic infarct size (r=0.388, p=0.004 at baseline; r=0.385, p=0.011 at follow-up) and inversely related to LVEF at both times (r=−0.484, p<0.001 at baseline; r=−0.461, p<0.001 at follow-up). Patients with adverse remodelling showed higher baseline copeptin values compared to patients without remodelling (p=0.02). Receiver operating characteristic analysis indicated a cut-off value of 16.7 pmol/l for copeptin to best identify patients with future adverse remodelling. Conclusions Increased copeptin values 2 days after STEMI are associated with larger acute and chronic infarct sizes. Moreover, elevated copeptin concentrations at baseline were associated with myocardial function and remodelling 4 months post-STEMI. These findings strengthen the role of copeptin as a biomarker of adverse outcome after STEMI.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: A collaborative meta-analysis

BACKGROUND Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Late microvascular obstruction after acute myocardial infarction: Relation with cardiac and inflammatory markers

OBJECTIVES We sought to assess the relation of late microvascular obstruction (l-MVO) size as quantified by cardiac magnetic resonance (CMR) imaging with cardiac and inflammatory marker concentrations after acute myocardial infarction (AMI). METHODS CMR was performed in 118 consecutive patients within 8 days after successful interventional reperfused first acute ST-elevation AMI. Infarct volumes and l-MVO sizes were calculated from late enhancement (LE) sequences and functional parameters were determined from short-axis cine MR sequences. Creatine kinase (CK) and cardiac troponin T (cTnT), high-sensitivity C-reactive protein (hs-CRP) as well as lactate dehydrogenase (LD) concentrations were determined serially from day 1 to day 4 after symptom onset. RESULTS L-MVO was detected in 66/118 patients (55.9%) and comprised 18.2 ± 10% of infarct size and 4.7 ± 3% of left ventricle myocardial mass. Each single-point, peak and cumulative release concentration of cTnT (r=0.44 to 0.73, p<0.0001), CK (r=0.21 to 0.76, p<0.0001), LD (r=0.36 to 0.82, all p<0.0001) as well as hs-CRP single-point values as assessed from day 1 to day 4 and its peak and cumulative release concentrations (r=0.24 to 0.49, p<0.003) significantly correlated with l-MVO size. Receiver operating curve (ROC) analysis indicated a cut-off value of 4.7 μg/l cTnT to best identify the presence of l-MVO (area under the curve (AUC) 0.904; 95% CI: 0.85-0.95; p<0.0001). CONCLUSION L-MVO sizes significantly correlate with cardiac and inflammatory marker concentrations as determined early after AMI. cTnT concentration of >4.7 μg/l could help to identify patients in whom l-MVO is present.

Early release of glycogen phosphorylase in patients with unstable angina and transient ST-T alterations.

OBJECTIVE--To determine whether transient ST-T alterations in patients with unstable angina are associated with an increase in plasma glycogen phosphorylase BB concentrations on admission to hospital. DESIGN--Prospective screening of patients with unstable angina for markers of myocardial cell damage. SETTING--Accident and emergency department of university hospital. PATIENTS--48 consecutive patients admitted for angina pectoris (18 with transient ST-T alterations). None of the patients had acute myocardial infarction according to standard criteria. MAIN OUTCOME MEASURES--Creatine kinase and creatine kinase MB activities, creatine kinase MB mass concentration, and myoglobin, cardiac troponin T, and glycogen phosphorylase BB concentrations on admission. RESULTS--All variables except for creatine kinase and creatine kinase MB activities were significantly higher on admission in patients with unstable angina and transient ST-T alterations than in patients without. However, glycogen phosphorylase BB concentration was the only marker that was significantly (p = 0.0001) increased above its discriminator value in most patients (16). In the 18 patients with transient ST-T alterations creatine kinase MB mass concentration and troponin T and myoglobin concentrations were significantly (p = 0.0001) less commonly increased on admission (in five, three, and two patients, respectively). CONCLUSIONS--The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.

Cardiac troponin T and creatine kinase predict mid‐term infarct size and left ventricular function after acute myocardial infarction: A cardiac MR study

To assess the relation of cardiac troponin T (cTnT) and creatine kinase (CK) release with infarct size and left ventricular function evaluated during the subacute phase as well as four months after acute myocardial infarction (AMI) by contrast‐enhanced MRI (CE‐MRI).

In search for the Holy Grail: Suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction: a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association

In search for the Holy Grail: Suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction : a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association