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Hugo A Katus

Publications and source records attributed to Hugo A Katus.

At least 91 records · Page 5Linked to original sources
PubMed2005

Complement receptors regulate lipopolysaccharide-induced T-cell stimulation.

Complement receptors type 1 and 2 (CR1 (CD35)/CR2 (CD21)) are known to enhance the adaptive immune response. In mice, CR1/CR2 are expressed on B cells, follicular dendritic cells, and activated granulocytes. Recently, we showed that a subset of CD44high and CD62Llow T cells also expresses CR1 and CR2. We now report that CR1/CR2 are detectable on both CD4+ and CD8+ subsets of T cells. Lipopolysaccharide (LPS) from Gram-negative bacteria causes polyclonal activation of B cells and stimulation of macrophages and other antigen-presenting cells. We further demonstrate that LPS induced marked up-regulation of CD25 and CD69 on T cells from CR1/CR2 sufficient (Cr+/+), but significantly lower up-regulation on T cells from CR1/CR2 deficient (Cr-/-) mice. These findings point to a novel mechanism by which CR1/CR2 modulates the activation of T cells by LPS.

Animals↗
PubMed2005

Determinants of B-type natriuretic peptide plasma levels in the chronic phase after heart transplantation.

Determinants of B-type natriuretic peptide (BNP) plasma levels in the chronic phase after heart transplantation remain unclear. BNP was measured in 105 stable long-term heart transplant recipients with normal left ventricular function by echocardiography and correlated with clinical, demographic and hemodynamic parameters. Multivariate analysis revealed a significant correlation of BNP with female recipient gender (P = 0.006), time post-transplant (P =0.006), donor age (P = 0.007), angiographic signs of transplant vasculopathy (TVP) (P = 0.03), serum creatinine level (P = 0.04), and a strong trend for diastolic dysfunction (P = 0.09). Donor gender, recipient age, cyclosporin A blood levels, rejection history, and pulmonary artery pressure had no independent effect on BNP. BNP after heart transplantation appears to be influenced both by established general determinants (female gender, renal function) and transplant-specific determinants such as time post-transplant, donor age and potentially also TVP. In order to determine the value of BNP as a potential surrogate marker of TVP serial intraindividual measurements appear appropriate.

Aged↗
PubMed2005

Changes in heart rate, heart rate variability, and heart rate turbulence during evolving reperfused myocardial infarction.

Depressed cardiac parasympathetic activity is associated with electrical instability and adverse outcomes after myocardial infarction (MI). Heart rate turbulence (HRT), reflecting reflex vagal activity, and heart rate variability (HRV), reflecting tonic autonomic variations are both reduced in the subacute phase of MI. However, the evolution of these components of cardiac autonomic control between subacute and chronic phase of MI has not been defined. We prospectively studied 100 consecutive patients with a recent first MI with ST-segment elevation, who underwent successful direct percutaneous coronary interventions. Beta-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors were administered according to the state-of-the-art medical practice guidelines. HRT and HRV were measured from 24-hour ambulatory electrocardiographic recordings 10 days and 12 months after the index MI. There was no significant difference in mean RR interval between the subacute and chronic phase of MI (875 +/- 145 versus 859 +/- 122 ms). Indices of HRV increased significantly during the observation period (SDNN: from 88.8 +/- 26.8 to 116.0 +/- 35.7 ms, P < 0.001; SDNNi: from 37.9 +/- 15.9 to 46.0 +/- 16.3 ms, P < 0.001; SDANN: from 79.6 +/- 34.7 to 105.6 +/- 35.4 ms, P < 0.001). In contrast, there were no significant changes in indices of HRT (turbulence onset: from -0.008 +/- 0.022 to -0.012 +/- 0.025%; turbulence slope: from 7.78 +/- 5.9 to 8.06 +/- 6.8 ms/beat). In contrast to reflex autonomic activity, there was a significant recovery of tonic autonomic activity within 12 months after MI. These different patterns of recovery of reflex versus tonic cardiac autonomic control after MI need to be considered when risk stratifying post-MI patients.

Aged↗
PubMed2005

Accelerated idioventricular rhythm in the post-thrombolytic era: incidence, prognostic implications, and modulating mechanisms after direct percutaneous coronary intervention.

BACKGROUND: In the thrombolytic era, the occurrence of accelerated idioventricular rhythm (AIR) has been proposed to be a specific marker for successful reperfusion. The incidence, prognostic implications, and potential modulating mechanisms of AIR after successful restoration of antegrade flow by means of modern reperfusion therapy (i.e., direct percutaneous coronary intervention (PCI)) has thus far not been investigated. METHODS: We prospectively investigated 125 consecutive patients undergoing direct PCI for a first acute myocardial infarction (AMI). The incidence of AIR was determined from 24-hour Holter monitoring, initiated prior to PCI. RESULTS: AIR appeared in 19 patients (15.2%). There were no significant differences between patients with or without AIR regarding baseline clinical characteristics. The incidence of AIR was not different between patients with TIMI 2 and 3 flow (13% vs 16%). There were no differences in the incidence of major cardiac events within 12-month follow-up in patients with and without AIR. Patients with AIR exhibited higher mean R-R intervals (mean 24-hour R-R interval: 871.3 +/- 121 vs 796.4 +/- 100 ms, P < 0.01), higher hourly mean values of heart rate variability (SDNN, 64.7 +/- 26 vs 49.4 +/- 20 ms, P < 0.01; rMSSD, 29.3 +/- 15 vs 22.0 +/- 12 ms, P < 0.01) and lower serum norepinephrine concentrations (60 minute after PCI, 478.9 +/- 357 vs 649.0 +/- 499 pg/ml, P < 0.05). CONCLUSIONS: Our findings indicate that AIR is an nonspecific marker for reperfusion of the infarct-related artery in AMI and thus, predate previous observations of the thrombolytic era. Even though, AIR was associated with higher tonic vagal tone and lower sympathetic activity, the occurrence of AIR had no prognostic impact on the clinical course and was not able to discriminate between complete and incomplete reperfusion.

Angioplasty, Balloon, Coronary↗
PubMed2004

Direct block of hERG potassium channels by the protein kinase C inhibitor bisindolylmaleimide I (GF109203X).

OBJECTIVE: The human ether-a-go-go-related gene (hERG) encodes the rapid component of the cardiac repolarizing delayed rectifier potassium current, I(Kr). The direct interaction of the commonly used protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM I) with hERG, KvLQT1/minK, and I(Kr) currents was investigated in this study. METHODS: hERG and KvLQT1/minK channels were heterologously expressed in Xenopus laevis oocytes, and currents were measured using the two-microelectrode voltage clamp technique. In addition, hERG currents in stably transfected human embryonic kidney (HEK 293) cells, native I(Kr) currents and action potentials in isolated guinea pig ventricular cardiomyocytes were recorded using whole-cell patch clamp electrophysiology. RESULTS: Bisindolylmaleimide I blocked hERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner with IC(50) values of 1.0 and 13.2 muM, respectively. hERG channels were primarily blocked in the open state in a frequency-independent manner. Analysis of the voltage-dependence of block revealed a reduction of inhibition at positive membrane potentials. BIM I caused a shift of -20.3 mV in the voltage-dependence of inactivation. The point mutations tyrosine 652 alanine (Y652A) and phenylalanine 656 alanine (F656A) attenuated hERG current blockade, indicating that BIM I binds to a common drug receptor within the pore region. KvLQT1/minK currents were not significantly altered by BIM I. Finally, 1 muM BIM I reduced native I(Kr) currents by 69.2% and lead to action potential prolongation. CONCLUSION: In summary, PKC-independent effects have to be carefully considered when using BIM I as PKC inhibitor in experimental models involving hERG channels and I(Kr) currents.

Action Potentials↗
PubMed2004

Mice lacking calsarcin-1 are sensitized to calcineurin signaling and show accelerated cardiomyopathy in response to pathological biomechanical stress.

Signaling by the calcium-dependent phosphatase calcineurin profoundly influences the growth and gene expression of cardiac and skeletal muscle. Calcineurin binds to calsarcins, a family of muscle-specific proteins of the sarcomeric Z-disc, a focal point in the pathogenesis of human cardiomyopathies. We show that calsarcin-1 negatively modulates the functions of calcineurin, such that calcineurin signaling was enhanced in striated muscles of mice that do not express calsarcin-1. As a consequence of inappropriate calcineurin activation, mice with a null mutation in calsarcin-1 showed an excess of slow skeletal muscle fibers. The absence of calsarcin-1 also activated a hypertrophic gene program, despite the absence of hypertrophy, and enhanced the cardiac growth response to pressure overload. In contrast, cardiac adaptation to other hypertrophic stimuli, such as chronic catecholamine stimulation or exercise, was not affected. These findings show important roles for calsarcins as modulators of calcineurin signaling and the transmission of a specific subset of stress signals leading to cardiac remodeling in vivo.

Adrenergic beta-Agonists↗
PubMed2004

Class Ia anti-arrhythmic drug ajmaline blocks HERG potassium channels: mode of action.

Ajmaline is a class Ia anti-arrhythmic drug used in several European countries and Japan as first-line treatment for ventricular tachyarrhythmia. Ajmaline has been reported to induce cardiac output (QT) prolongation and to inhibit cardiac potassium currents in guinea pig cardiomyocytes. In order to elucidate the molecular basis of these effects, we examined effects of ajmaline on human ether a-go-go related gene HERG potassium channels. Electrophysiological experiments were performed with human embryonic kidney (HEK) cells (whole-cell patch clamp) and Xenopus oocytes (double-electrode voltage clamp) expressing wild-type and mutant HERG channels. Ajmaline blocked HERG currents with an IC(50) of 1.0 micromol/l in HEK cells and 42.3 micromol/l in Xenopus oocytes. The onset of block was fast and reached steady-state conditions after 180 s. The inhibitory effect was completely reversible upon wash-out. In HERG mutant channels Y652A and F656A lacking aromatic residues in the S6 domain, the inhibitory effect of ajmaline was completely abolished. Ajmaline induced a small shift in HERG current half-maximal activation voltage towards more negative potentials. Ajmaline did not markedly affect HERG inactivation. Inhibitory effects were not voltage-dependent. Ajmaline block exhibited positive frequency dependence. Ajmaline blocked HERG channels in the open, but not in the closed states. Binding of ajmaline to inactivated HERG channels may also be possible. In inactivation-deficient HERG S620T channels, the sensitivity to ajmaline was markedly reduced. The IC(50) of HERG channel blockade in HEK cells lies within the range of unbound therapeutic plasma concentrations of ajmaline. Therefore, inhibitory effects on HERG channels may contribute to both the high anti-arrhythmic efficacy of ajmaline and to its pro-arrhythmic potential.

Action Potentials↗
PubMed2004

Are QT measurements on body surface ECG indicative of ventricular refractory patterns?

OBJECTIVE: Increased dispersion (DISP) of refractoriness (ERP) facilitates the induction of malignant ventricular arrhythmias. Accordingly, QT DISP on surface ECG, supposedly reflecting ERP DISP, has been proposed as a noninvasive marker for risk stratification. However, a comparative analysis of local ERPs and QT measurements is not available so far. METHODS AND RESULTS: In 19 healthy dogs, standard 12 lead surface ECGs were recorded to measure QT and RR intervals. Based on these measurements, corrected QT intervals (QTc, Bazett formula) and DISP (maximum difference) of both QT and QTc intervals (QT-DISP and QTc-DISP, respectively) were calculated. Subsequently, 60 custom-made needle electrodes (12 mm long, 4 bipolar electrodes per needle, interelectrode distance 2.5 mm) were inserted into the left (LV) and right ventricle (RV). At each bipole of 14 randomly selected needle electrodes (8 LV, 6 RV) local ERPs were determined (extrastimulus technique, basic cycle length 1000 ms). Interventricular DISP of ERP (LV-RV-DISP) was defined as the difference between the longest and shortest ERP within both ventricles. Respective values were calculated for each ventricle (LV-DISP; RV-DISP). Scatter plots and correlation analysis did not reveal a significant correlation between QT, QTc, QT-DISP, QTc-DISP and any of the ERP measurements or calculations. Although not statistically significant, the closest correlation was found between QTc and mean ERP and between QTc-DISP and LV-RV-DISP. CONCLUSION: QT measurements on surface ECG are poorly correlated with local ERPs. If anything, QT- or QTc-DISP might provide a rough estimate of interventricular, that is, global DISP of ERP. Local or even intraventricular DISP of ERP is definitely not reflected by these QT measurements.

Animals↗
PubMed2004

Platelet-derived growth factor induces tissue factor expression in vascular smooth muscle cells via activation of Egr-1.

Activation of vascular smooth muscle cells (SMCs) by platelet-derived growth factor (PDGF) is a seminal event in the initiation and progression of the atherosclerotic lesion and may contribute to atherosclerotic plaque instability with plaque rupture and thrombus formation. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play a major role in thrombus formation after plaque rupture. This study examined intracellular signaling pathways leading to TF expression and Egr-1 activation, a key element in tissue factor transcription, by PDGF-BB in rat SMCs. PDGF-BB induced TF mRNA and protein expression in a time-dependent manner. Early growth response factor-1 (Egr-1) binding activity was also induced by PDGF-BB, as well as phosphorylation of extracellular signal-regulated kinase. PDGF-BB-induced Egr-1 activation was suppressed by inhibitors of 2 upstream activators of Egr-1, extracellular signal-regulated kinase (ERK) and Src family kinases, whereas antioxidants, phosphatidylinositol 3-phosphate kinase, and p38 MAPK inhibitors had no effect. PDGF-BB-stimulated expression of the transcriptional co-repressor NAB2 was time-dependent. Furthermore, transient transfections of SMCs with wild-type and mutated TF promoter constructs showed that the Egr-1 binding region is an important transcriptional regulator of PDGF-BB-induced TF expression. Taken together, the results suggest that PDGF-BB induces TF expression and activity in SMC by a Src family kinases/ERK/Egr-1 signaling pathway and may therefore contribute to thrombus formation in advanced atherosclerosis and restenosis.

Animals↗
PubMed2004

Cardiac biomarkers for detection of myocardial infarction: perspectives from past to present.

With great pleasure and anticipation in recognition of Clinical Chemistry's 50th anniversary, I have been able to arm-twist four talented scientists to document their impressive marks on the science of diagnostics in the field of cardiac biomarkers and detection of myocardial infarction. Their exciting discoveries and applications have dramatically influenced the fields of laboratory medicine and cardiology and have greatly influenced the care and management of thousands of patients suffering from coronary artery disease leading to acute myocardial infarction. As a matter of historical record, I owe a great deal of thanks to each one of the coauthors of this special report because each one has personally influenced my scientific career. I met Dr. Rosalki, during my postdoctoral training, at a national AACC meeting, where he kindly answered my numerous queries regarding creatine kinase enzymology and muscle physiology. Dr. Roberts, while serving as Director of the Coronary Care Unit at Washington University in St. Louis, generously allowed this fledgling fellow into his laboratory and shared many of his clinical and experimental findings with me. Dr. Katus, whom I first met at a scientific meeting sponsored by Boehringer Mannheim in 1986 in Bavaria, where I first became fascinated with cardiac troponin T, has remained a friend and colleague. Lastly, Dr. Ladenson, who as mentor, scientific colleague, and close friend remains ultimately responsible for both my professional growth as a clinical chemist (he was my postdoctoral fellowship advisor) and for stimulating and encouraging my goals and aspirations in the field of cardiac biomarkers. With the descriptions of the ground-breaking science described below, I am extremely excited and optimistic that the future of cardiac biomarkers is secure and open to new discoveries by the Rosalkis, Robertses, Katuses, and Ladensons of the future.

Biomarkers↗
PubMed2004

Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

BACKGROUND: The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion. METHODS AND RESULTS: Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP). CONCLUSIONS: NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Adrenergic beta-Antagonists↗
PubMed2004

Activation of cardiac human ether-a-go-go related gene potassium currents is regulated by alpha(1A)-adrenoceptors.

Patients with cardiac disease typically develop life-threatening ventricular arrhythmias during physical or emotional stress, suggesting a link between adrenergic stimulation and regulation of the cardiac action potential. Human ether-a-go-go related gene (hERG) potassium channels conduct the rapid component of the repolarizing delayed rectifier potassium current, I(Kr). Previous studies have revealed that hERG channel activation is modulated by activation of the beta-adrenergic system. In contrast, the influence of the alpha-adrenergic signal transduction cascade on hERG currents is less well understood. The present study examined the regulation of hERG currents by alpha(1A)-adrenoceptors. hERG channels and human alpha(1A)-adrenoceptors were heterologously coexpressed in Xenopus laevis oocytes, and currents were measured using the two-microelectrode voltage clamp technique. Stimulation of alpha(1A)-receptors by applying 20 microM phenylephrine caused hERG current reduction due to a 9.6-mV shift of the activation curve towards more positive potentials. Simultaneous application of the alpha(1)-adrenoceptor antagonist prazosin (20 microM) prevented the activation shift. Inhibition of PKC (3 microM Ro-32-0432) or PKA (2.5 microM KT 5720) abolished the alpha-adrenergic activation shift, suggesting that PKC and PKA are required within the regulatory mechanism. The effect was still present when the PKA- and PKC-dependent phosphorylation sites in hERG were deleted by mutagenesis. In summary, cardiac repolarizing hERG/I(Kr) potassium currents are modulated by alpha(1A)-adrenoceptors via PKC and PKA independently of direct channel phosphorylation. This novel regulatory pathway of alpha1-adrenergic hERG current regulation provides a link between stress and ventricular arrhythmias, in particular in patients with heart disease.

Animals↗
PubMed2004

Human cardiac inwardly rectifying current IKir2.2 is upregulated by activation of protein kinase A.

OBJECTIVE: The cardiac inwardly rectifying potassium current IK1 and its molecular correlates Kir2.1 and Kir2.2 play an important role in cardiac repolarisation and in the pathogenesis of hereditary long-QT syndrome (LQTS-7). Protein kinases A (PKA) and C (PKC) are key enzymes in adrenergic signal transduction, inducing arrhythmias in heart disease. This study investigated the regulation of Kir2.2 (KCNJ12) by PKA. METHODS: Cloned Kir2.2 channels were expressed heterologously in Xenopus oocytes and currents were measured with the double-electrode voltage-clamp technique. RESULTS: After activation of PKA by forskolin (100 micromol/l) or Ro-20-1724 (100 micromol/l), wild type currents at -120 mV were increased by 93.7% and 79.0%, respectively. Coapplication of the PKA inhibitor KT-5720 (2.5 micromol/l) attenuated this effect. No significant changes were apparent after mutation of the single PKA consensus site S430. In addition, removal of all four PKC consensus sites in Kir2.2 induced a phorbolester-mediated current increase which could be suppressed by PKA inhibitors H-89 (50 micromol/l) and KT-5720 (2.5 micromol/l). CONCLUSIONS: This study demonstrates antagonistic effects of PKA and PKC in the regulation of Kir2.2. Phosphorylation by PKC has been shown to cause an inhibition of Kir2.2 currents, whereas activation of PKA leads to current upregulation.

Animals↗
PubMed2004

Primary pulmonary hypertension in children may have a different genetic background than in adults.

Mutations of the bone morphogenetic protein receptor II (BMPR2) gene on chromosome 2q33 can cause familial primary pulmonary hypertension (PPH) and may occur in 26% adult patients with sporadic disease. Other disease-related genes have been localized to chromosomes 2q31 (PPH2) and 12q13 (ALK1). The genetic background in affected children remains unclear. Thirteen children (age at diagnosis, 6 mo to 13 y; mean, 5.6 +/- 3.9 y) with invasively confirmed PPH were screened for BMPR2 mutations using denaturing HPLC and sequence analysis. In addition, all children were scanned for BMPR2 deletions by Southern blot analysis. Pulmonary artery pressure was assessed using echocardiography at rest and during exercise in 57 family members of six infants. The six families were subjected to linkage analysis. None of the 13 children had a BMPR2 mutation or deletion. Linkage to chromosome 2 or 12 could not be confirmed in any of the families investigated. In all assessed families, both parents of the index patient and/or members of both branches revealed an abnormal pulmonary artery systolic pressure (PASP)-response to exercise. PPH in children may have a different genetic background than in adults. We postulate a recessive mode of inheritance in a proportion of infantile cases.

Adolescent↗
PubMed2004

Inhibition of cardiac HERG potassium channels by the atypical antidepressant trazodone.

Trazodone is an atypical antidepressant that is commonly used in the treatment of affective disorders. There have repeatedly been reports of cardiac arrhythmia associated with this drug and concerns have been raised regarding the cardiac safety of trazodone. However, interaction with HERG channels as a main factor of cardiac side effects has not been studied to date. Therefore, we investigated the effect of trazodone on HERG potassium channels expressed in human embryonic kidney (HEK) cells and in Xenopus oocytes. Trazodone inhibited HERG currents in a dose-dependent manner with an IC50 of 2.9 microM in HEK cells and 13.2 microM in Xenopus oocytes. The electrophysiological properties of HERG blockade were analysed in detail. In HERG channel mutants Y652A and F656A lacking aromatic residues in the S6 domain, the affinity of trazodone was reduced profoundly. Trazodone accelerated inactivation of HERG currents without markedly affecting activation. Blockade was voltage dependent with a small reduction of block at positive membrane potentials. Frequency dependence of block was not observed. Trazodone block of HERG channels was state dependent. Channels were affected in the activated and inactivated states, but not in the closed states. In summary, the atypical antidepressant trazodone blocks cardiac HERG channels at concentrations that are probably relevant in vivo, particularly in overdosage.

Animals↗
PubMed2004

Patient alert in implantable cardioverter defibrillators: toy or tool?

OBJECTIVES: The purpose of this study was to analyze the utility of patient-alert features in implantable cardioverter defibrillators (ICDs). BACKGROUND: Various alert features producing acoustic warning signals have been implemented in newer generation ICDs, but their role in early detection of system-related complications has not been systematically evaluated. METHODS: In 240 patients implanted with Medtronic ICD devices, the following alert features were routinely activated: pacing lead impedance <200 or >2,000 Omega, high-voltage lead impedance <10 or >200 Omega, low battery voltage (elective replacement indicator), long charge time (>18 s), >3 shocks delivered per episode, and all therapies in a zone delivered. Alert events occurring during follow-up were assessed in relation to actual findings (hospital charts, chest X-rays, ICD printouts including sensing/pacing/defibrillation threshold tests, episode data) to determine incidence, sensitivity, and specificity of the alert function. RESULTS: During 12.2 +/- 8.9 months, 24 alert events occurred in the 240 patients (pacing lead impedance, n = 4; high-voltage lead impedance, n = 7; low battery voltage, n = 1; >3 shocks, n = 6; all therapies, n = 6). A total of 22 serious complications (necessitating reprogramming or device/lead replacement) were observed, 14 of which were primarily identified through a patient alert (lead fracture, n = 11; connector defect, n = 1; T-wave oversensing, n = 1; battery depletion, n = 1). This reflects a sensitivity of 64% and a specificity of 96% of the alert function for serious complications. With 14 of 24 patient alerts being caused by serious complications, the positive predictive value reached 58%. CONCLUSIONS: Patient-alert features are a useful additional tool facilitating early detection of serious ICD complications, but they do not substitute for regular ICD follow-up, because of their low sensitivity.

Aged↗
PubMed2004

Cardiac troponin T for prediction of short- and long-term morbidity and mortality after elective open heart surgery.

BACKGROUND: Increased cardiac troponins in blood are observed after virtually every open heart surgery, indicating perioperative myocardial cell injury. We sought to determine the optimum time point for blood sampling and the respective cutoff value of cardiac troponin T (cTnT) for risk assessment in patients undergoing cardiac surgery. METHODS: In a series of 204 patients undergoing scheduled open heart surgery, mainly for coronary artery bypass grafting (n = 132) or valve repair (n = 27), cTnT concentrations were measured before and 4 and 8 h after cross-clamping and then daily for 7 days. Individual risk was assessed by use of the Cleveland Clinic Foundation Risk score and intraoperative risk indicators such as duration of cardiopulmonary bypass, cross-clamping, and perioperative release of cardiac markers. Patients were followed for 28 months. RESULTS: Cardiac mortality, all-cause mortality rates, and rates of nonfatal acute myocardial infarction (AMI) at 28 months were 6.9%, 8.8%, and 6.8%, respectively. cTnT was higher in patients with Q-wave AMI or postoperative heart failure requiring inotropic support, and in nonsurvivors. The ROC curve revealed a cTnT > or = 0.46 microg/L at 48 h as the optimum discriminator for long-term cardiac mortality. Stepwise logistic regression identified higher Cleveland Clinic Risk Score [odds ratio (OR) = 2.6 per point], cross-clamp time >65 min (OR = 6.6), and cTnT (OR = 4.9) as significant and independent predictors of long-term cardiac mortality. CONCLUSIONS: A single postoperative cTnT measurement can be used to estimate myocardial cell injury that impacts long-term survival after open heart surgery. It adds independently to established risk indicators.

Aged↗