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Biomedical subjects

Johannes Mair

Publications and source records attributed to Johannes Mair.

At least 19 recordsLinked to original sources

Utility of N-terminal pro-B-type natriuretic peptide to differentiate cardiac diseases from noncardiac diseases in young pediatric patients.

BACKGROUND: Previous studies comparing children with cardiac disease with children with lung disease or healthy children indicated that natriuretic peptides are promising markers in pediatric patients. The aim of this study was to further clarify the diagnostic usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements in a less preselected population of children younger than 3 years, a population in which clinical symptoms are frequently unspecific. METHODS: NT-proBNP concentrations (Roche Diagnostics) were measured in sera of 142 pediatric patients (age range, 33-1070 days) presenting at the Gynaecologic and Pediatric Hospital (Linz, Austria) between January 2003 and January 2004. ROC curve analysis for the diagnostic performance of NT-proBNP, the Mann-Whitney U-test for group comparison, and linear regression analysis for influencing factors were performed. RESULTS: NT-proBNP concentrations were significantly increased in infants with cardiac diseases [median (25th-75th percentile), 3681 (1045-13557) ng/L; n = 23] compared with infants with other diseases [241 (116-542) ng/L; n = 119], and ROC analysis revealed good performance for NT-proBNP in differentiating between infants with and without cardiac diseases [mean area under the curve (AUC) with 95% confidence interval (CI), 0.87 (0.76-0.94)]. A subgroup analysis of exactly age- and sex-matched infants was performed, which revealed results comparable to those for the whole study population [mean (95% CI) AUC, 0.84 (0.68-0.93)]. CONCLUSION: In a heterogeneous group of pediatric patients < 3 years of age, NT-proBNP showed good diagnostic performance to distinguish between cardiac diseases and various noncardiac diseases.

Brain Diseases↗

Short-term improvement in submaximal exercise capacity by optimized therapy with ACE inhibitors and beta blockers in heart failure patients is associated with restoration of peripheral endothelial function.

BACKGROUND: Improved exercise capacity in chronic heart failure (CHF) has been attributed to restoration of endothelial function. ACE inhibitors as well as beta blockers have previously been shown to enhance endothelial function and exercise capacity. The aim of this study was to determine whether short-term improvement in submaximal exercise capacity induced by optimized therapy with ACE inhibitors in combination with beta blockers is associated with restoration of endothelial function in CHF patients. METHODS: Thirty-three patients with CHF were evaluated: six-minute walk test, NYHA class, brain natriuretic peptide (BNP), big Endothelin-1 (bigET-1) and flow-mediated vasodilation (FMD) of the brachial artery were assessed at baseline and after a 3-month period of optimized neurohormonal therapy. Two groups were formed retrospectively based on the changes in submaximal exercise capacity (responders and non-responders). RESULTS: Optimization of neurohormonal therapy was comparable between groups. Responders (n=17) revealed a significant increase in walking distance (304+/-109 to 441+/-75 m; p<0.01), which was paralleled by a decrease in NYHA class (2.7+/-0.6 to 2.0+/-0.4; p<0.01), BNP (484+/-454 to 243+/-197 pg/ml; p<0.01), and bigET-1 (2.0+/-0.9 vs. 1.5+/-0.6 fmol/ml; p=0.04). By contrast, the latter variables did not change in non-responders. Improvement in functional capacity in responders was associated with an increase in FMD (8.2+/-3.9% to 11.0+/-5.6%; p<0.05). Increments in FMD were directly correlated with increases in walking distance (r=0.34; p<0.05). CONCLUSION: Short-term improvement of submaximal exercise capacity in CHF patients following optimized therapy with ACE inhibitors and beta blockers is associated with restoration of endothelial function in conduit arteries.

Adrenergic beta-Antagonists↗

Direct comparison of relaxation and cGMP production in human coronary by-pass grafts in response to stimulation with natriuretic peptides and a nitric oxide donor.

In the present study, we investigated the vasodilator properties of A-type, B-type and C-type natriuretic peptides (ANP, BNP and CNP respectively) and the NO (nitric oxide) donor sin-1 (3-morpholino-sydnonimine) in human by-pass grafts. In contrast with previous studies, the same vessel was used to demonstrate a direct link between cGMP production and functional relaxation. Remnants of the IMA (internal mammary artery) and SV (saphenous vein) were obtained from 82 patients undergoing coronary artery by-pass grafting. The responses to cumulative concentrations of ANP, BNP, CNP and sin-1 in vessel rings pre-contracted with a thromboxane A2 agonist (U46619) were measured in an organ bath. Additionally, intracellular cGMP production after single submaximal dose application of these drugs to vessel rings was determined by a RIA. ANP (P=0.001) and sin-1 (P<0.001) caused significant concentration-dependent relaxation of the IMA. In the SV, only sin-1 (P<0.001) induced marked concentration-dependent relaxation. At a single submaximal concentration, significant relaxation as well as intracellular cGMP production were found in response to ANP, BNP and sin-1 in the IMA. In contrast, in the SV, only sin-1 significantly induced cGMP production and relaxation. There was a moderate, but significant, correlation between intracellular cGMP net production and net relaxation in the IMA. In conclusion, ANP, as the most powerful relaxant of all the natriuretic peptides tested on the IMA, may be a possible alternative vasorelaxant to overcome peri-operative vasospasm in this artery. In contrast with sin-1, ANP and BNP were not effective vasorelaxants of the SV. Net relaxation in response to natriuretic peptides correlated with cGMP net concentrations in the IMA.

Adult↗

Thermal preconditioning protects the human internal mammary artery from hypoxia/re-oxygenation-induced damage.

1. Preconditioning has been demonstrated to ameliorate ischaemia/reperfusion injury in several cells and tissues. Therefore, in the present study we investigated whether preconditioning of human bypass grafts, internal mammary artery (IMA) and saphenous vein (SV) induces heat shock protein (Hsp) expression and reduces apoptosis in response to subsequent hypoxia/re-oxygenation damage in both vessels. 2. Internal mammary artery and SV rings, obtained from 30 patients (median age 66.5 years) undergoing coronary artery bypass grafting, were either incubated for 30 min at 42 degrees C (preconditioned) or kept in a standard incubator at 37 degrees C (not preconditioned). Six hours later, graft segments were exposed to 90 min hypoxia followed by a 30 min re-oxygenation period. Western blot, real-time quantative polymerase chain reaction analysis and apoptosis detection by the Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling method were performed. 3. Heat-preconditioned IMA showed significantly increased protein expression of Hsp72 after hypoxia/re-oxygenation treatment compared with controls (median 9.1 vs 5.0 microg/mg total protein; P = 0.048). Expression of Hsp73 was weak and Hsp60 was not detectable in the IMA. 4. In the SV, neither protein nor mRNA expression of Hsp were significantly different between preconditioned and not preconditioned veins. 5. There were significantly fewer apoptotic cells in the intima of the preconditioned compared with not preconditioned IMA (P = 0.041) after hypoxia/re-oxygenation injury, whereas in the SV apoptosis was not significantly prevented by preconditioning. 6. Mild heat preconditioning before hypoxia/re-oxygenation injury is a stimulus for Hsp72 protein expression and a reduction in apoptosis in the human IMA.

Aged↗

Transient impairment of flow-mediated vasodilation in patients with metabolic syndrome at moderate altitude (1,700 m).

BACKGROUND: The influence of moderate altitude on the cardiovascular system in patients with metabolic syndrome has not been investigated sufficiently, yet. The aim of this study was to assess the effect of acute and mid-term exposure to moderate altitude (1,700 m) on endothelial function in patients with metabolic syndrome. METHODS: Flow-mediated (FMD) and nitroglycerin-mediated vasodilation (NMD) were assessed in 18 patients with coronary risk factors on 5 occasions: (1) at location A (576 m), (2) on the first day at moderate altitude (location B, 1,700 m), (3) after 3 weeks at moderate altitude, (4) and (5) again at location A (6 and 16 weeks after the stay at moderate altitude, respectively). In addition, markers of lipid metabolism, serum erythropoietin and endothelin were measured. RESULTS: FMD on the first day at moderate altitude was similar compared to baseline FMD at location A (7.0 +/- 3.3 vs. 7.4 +/- 4.6%; NS). A 3-week stay at moderate altitude was associated with a significant reduction in FMD (7.4 +/- 4.6 vs. 3.8 +/- 2.5%; p < 0.05) despite a decrease in baseline diameter (4.5 +/- 0.3 vs. 4.3 +/- 0.4 mm; p < 0.05). Six weeks after returning to location A, FMD was still reduced compared to baseline (4.3 +/- 2.8%; p < 0.05) and after further 16 weeks, FMD returned to baseline values (5.5 +/- 3.5%). However, metabolic parameters improved significantly. In contrast, NMD and endothelin levels remained unchanged. CONCLUSION: In patients with metabolic syndrome, a sojourn of 3 weeks at moderate altitude leads to a prolonged, but reversible impairment of FMD. The discrepancy to improvement of other cardiovascular and metabolic parameters requires further investigation.

Adult↗

Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.

Acute Disease↗

Chronic heart failure is associated with vascular remodeling of the brachial artery.

AIMS: Endothelial dysfunction has been shown to correlate with severity of congestive heart failure (CHF) and recent data suggest morphological changes of peripheral vasculature to be associated with the syndrome. We therefore investigated the hypothesis that vascular remodeling is associated with functional changes in peripheral conduit arteries and with systemic overexpression of ET-1 in patients suffering from CHF. METHODS AND RESULTS: 57 consecutive patients referred to the Innsbruck Heart Failure and Transplantation Program (EF=23+/-7%) and 16 matched controls (EF=60+/-5%) were studied. Flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), wall thickness (WT), and incremental elastic modulus (Einc) were assessed by high-resolution ultrasound of the brachial artery. FMD (P=0.004) and NMD (P=0.02) were significantly higher in controls as compared to moderate and severe CHF patients. In contrast, brachial artery-wall thickness (BA-WT) was increased in severe CHF patients (P=0.038). BA-WT was significantly correlated with both FMD (r=-0.28; P=0.049) and NMD (r=-0.38; P=0.003), and with the Einc (r=0.45, P=0.001). Lumen diameter was not different among groups. In patients with BA-WT>0.31 mm, bigET-1 was higher compared to BA-WT<0.31 mm (P<0.05). CONCLUSION: CHF is associated with remodeling of the brachial artery, which is characterized by morphological, mechanical and functional changes of the vessel wall. Endothelin-1 may play a role in the vascular remodeling process.

Adult↗

B-type natriuretic peptide as a marker of allograft rejection after heart transplantation.

B-type natriuretic peptide (BNP) concentrations, a cardiac hormone released upon cardiac stress, was monitored in patients after heart transplantation. Rejection was assessed by the International Society for Heart and Lung Transplantation (ISHLT) criteria. BNP was assessed by a cross-sectional approach. We found significantly (p = 0.024) increased concentrations during rejection episodes of ISHLT grade 2 and higher. BNP yielded only a moderate diagnostic accuracy (area under the receiving characteristic curve: mean = 0.76, 95% confidence interval 0.53-0.92) to detect clinically significant episodes of rejection, which was too low to replace endomyocardial biopsies. Acute rejection episodes were associated with marked BNP increases and a significant decrease in case of successful treatment in the individual long-term monitoring in the majority of patients. BNP monitoring seems to be a useful addition in the individual follow-up of heart transplant recipients to rule out significant rejection.

Adult↗

Monitoring of patients with heart failure.

The recent guidelines of the European Society of Cardiology, recommends laboratory testing as an essential part of the evaluation of the patient presenting with acute or chronic heart failure. The decrease in BNP has been included as a treatment goal for the management of acute heart failure. As for other properties it is important to define what difference can be considered as a real change of the marker in serial measurements. Therefore, knowledge of pathophysiological influences and pre-analytical issues as well as the intraindividual variability of BNP and N-terminal proBNP (NT-proBNP) due to analytical imprecision and biological variation is crucial. Erroneous test results with BNP or NT-proBNP assays are rare but may occasionally occur analytical interferences and should be suspected if the results do not suit the clinical picture or the serial kinetics. Although BNP assays correlate closely, due to lack of standardization no two BNP assays are analytically equivalent, and the same assay must be used for serial measurement. The in-vitro stabilities of BNP and NT-proBNP are sufficient for routine use, and blood sampling for BNP or NT-proBNP directly after arrival without a standardized period of rest is feasible, however, heavy physical exercise should be avoided before blood sampling. To be on the safe side a period of 10 minutes rest before blood sampling is recommended. BNP and NT-proBNP are suitable for heart failure monitoring, and BNP and NT-proBNP changes >50% from baseline correlated well with clinical course and a reduction of mortality in heart failure patients.

Heart Failure↗

Quality specifications for B-type natriuretic peptide assays.

BACKGROUND: The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. METHODS: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. RESULTS: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. CONCLUSIONS: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

Biomarkers↗

Markers for perioperative myocardial ischemia: what both interventional cardiologists and cardiac surgeons need to know.

All novel markers of myocardial ischemia (ischemia-modified albumin, choline, unbound free fatty acids) lack cardiac specificity. Therefore, for the specific detection of myocardial ischemia selective blood sampling from an inserted coronary sinus catheter is needed, which limits the applicability of these markers in most clinical routine settings. In addition, the superiority of these novel markers over the calculation of myocardial lactate production, the current criterion standard for the laboratory diagnosis of myocardial ischemia, has not been demonstrated so far, and even comparative data is frequently lacking. Further the superiority of these new candidate markers over lactate determination for the diagnosis of myocardial ischemia in peripherally drawn blood samples has not been demonstrated either, and these novel parameters appear not to be a breakthrough for laboratory diagnosis of myocardial ischemia during or after percutaneous coronary interventions or coronary artery bypass grafting. The determination of cardiac troponin I or troponin T is the current criterion standard for the laboratory diagnosis of myocardial damage due to their higher sensitivities and specificities compared to creatine kinase isoenzyme MB. According to current knowledge, troponin increases in peripherally drawn blood samples must be regarded as an indicator of myocardial necrosis which, however, may be limited, only detectable by troponin and may be missed by creatine kinase isoenzyme MB determination. After on-pump coronary artery bypass grafting the generally applied troponin discriminator limits are not valid as there is limited, inevitable cardiac tissue damage occurring during the surgical procedure. Therefore, troponins are significantly increased after reperfusion of the arrested heart over values seen before bypass and also in patients without complications. Perioperative myocardial infarctions can be reliably identified by their characteristic troponin time courses, and both peak concentrations and time of peak values are diagnostic criteria. Troponin release is lower in off-pump compared to on-pump bypass surgery. Despite the controversy over the significance of troponin elevations after clinically uncomplicated and successful procedures, it is tempting to postulate that less myocardial damage as detected by troponin release is beneficial for the patient. After elective percutaneous coronary interventions, only troponin increases >8-fold the upper reference limit were associated with increased mortality in long-term follow-up.

Angioplasty, Balloon, Coronary↗

Natriuretic peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnostic performance of markers.

BACKGROUND: We compared the performance of different natriuretic peptides to diagnose mild forms of left ventricular dysfunction (LVD) and investigated the influence of measuring B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) with different assays on the diagnostic performance of these markers. METHODS: We measured BNP (Triage BNP), NT-proBNP (Biomedica), and N-terminal pro-A-type natriuretic peptide (NT-proANP; Biomedica) in 130 consecutive patients (age range, 28-83 years) with clinically suspected mild LVD. In patients with sufficient sample volume, we measured BNP and NT-proBNP with additional assays (Shionoria and Roche, respectively). RESULTS: For identifying patients with mild systolic LVD, BNP and NT-proBNP were the best markers, with mean (95% confidence interval) areas under the curves (AUC) of 0.78 (0.63-0.89) and 0.75 (0.58-0.87), respectively. However, the diagnostic performance of NT-proANP [AUC, 0.64 (0.48-0.77)] was significantly worse than that of BNP (P = 0.014). Both BNP assays (Triage and Shionoria) and both NT-proBNP assays (Biomedica and Roche) performed equally well for the diagnosis of systolic LVD despite the poor agreement between NT-proBNP assays. In patients with isolated diastolic LVD, the diagnostic performance of the Triage BNP [AUC, 0.70 (0.56-0.81)] was significantly better (P = 0.006) than that of Biomedica NT-proBNP [0.49 (0.34-0.65)]. Furthermore, the performance of the Biomedica NT-proBNP assay was significantly worse (P = 0.03) than that of the Roche NT-proBNP assay for diagnosis of isolated diastolic LVD. CONCLUSIONS: The performance of BNP for the diagnosis of systolic or diastolic LVD is not affected by the assay used, whereas the performance of NT-proBNP for the diagnosis of isolated diastolic LVD is assay dependent.

Adult↗

Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study.

BACKGROUND: B-Type natriuretic peptide (BNP) is released from the left ventricle of the heart into the circulation in response to ventricular stretching and volume overload. Increased BNP concentrations are associated with heart failure (HF). METHODS: We evaluated the analytical and clinical performance of the Bayer ADVIA Centaur BNP assay. Studies included precision, analytical correlation (against the Shionogi ShionoRIA and Biosite Triage BNP assays), BNP results for blood collected in plastic tubes containing EDTA vs other collection tubes, high-dose hook effect, detection limits, and interferences. The clinical performance was tested on 2243 blood samples collected from 983 apparently healthy individuals, 538 patients with chronic disease but without HF (renal insufficiency, chronic obstructive pulmonary disease, diabetes, and hypertension), and 722 patients with HF (New York Heart Association classes I-IV). RESULTS: The ADVIA Centaur assay had total imprecision (CV) of 3.4%, 2.9%, and 2.4% at BNP concentrations of 48, 461, and 1768 ng/L, respectively. The Passing-Bablok correlations to the ShionoRIA and Triage were as follows: ADVIA Centaur = 1.11(ShionoRIA) - 1.19 ng/L (r = 0.98); ADVIA Centaur = 0.78(Triage) + 5.89 ng/L (r = 0.92), respectively. Of the different blood collection tubes, only EDTA plastic tubes (with and without the barrier gel) were acceptable. The lower detection limit was 0.5 ng/L, and there were no interferences from common analytes, other neuropeptides, or unusual antibodies. BNP exhibited different reference intervals according to age and gender. BNP concentrations increased progressively as the severity of HF increased. CONCLUSIONS: The ADVIA Centaur is the first commercially available BNP assay for use on an automated immunochemistry platform. This assay has good analytical and clinical performance characteristics for diagnosing HF.

Adult↗