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Biomedical subjects

H Katus

Publications and source records attributed to H Katus.

At least 19 recordsLinked to original sources

Effect of stress-induced reversible ischemia on serum concentrations of ischemia-modified albumin, natriuretic peptides and placental growth factor.

OBJECTIVE: There is controversy whether new biomarkers are able to identify myocardial ischemia in the absence of myonecrosis. METHOD: We measured NT-pro BNP, NT-pro ANP, ischemia-modified albumin (IMA) and placental growth factor (PlGF) in patients undergoing nuclear stress testing for suspected ischemic heart disease. A thallium scan was used for detection of reversible myocardial ischemia and cardiac troponin T (cTnT) for exclusion of stress-induced myonecrosis. Of 195 patients, 24 with reversible and 62 with no perfusion defect were included in the analysis. Plasma levels were measured before, 18 min and 4 h after stress testing. RESULTS: Of the 86 patients, 52 received an exercise stress and 34 dipyridamol. New myonecrosis indicated by cTnT could be excluded in all patients. Plasma levels of NT-pro BNP and NT-pro ANP before testing were significantly higher in patients who later developed reversible perfusion defects (NT-pro BNP 139.00 (58.25/367.01) pg/mL vs 327.45 (120.50/972.85) pg/mL, p<0.05; NT-pro ANP 732.5 (470.0/1220.0) pg/mL vs 1470.0 (694.0/1910.0) pg/mL, p<0.05). Plasma levels of NT-pro BNP, NT-pro ANP and PIGF did not change significantly after stress testing, IMA levels rose significantly after 4 h in patients with and without reversible perfusion defects. CONCLUSION: The elevation of NTpro BNP and NT-pro ANP at baseline may represent the cumulative effect of repeated bouts of myocardial ischemia. A single brief episode of provoked ischemia does not cause a significant increase of the measured biomarkers beside from IMA after exercise stress test potentially indicating skeletal muscle ischemia.

Aged↗

Plasma catecholamines and N-terminal proBNP in patients with acute myocardial infarction undergoing primary angioplasty. Relation to left ventricular function and clinical outcome.

BACKGROUND: Neither profiles nor prognostic values of neurohormonal markers have been prospectively evaluated in patients with acute myocardial infarction (AMI) undergoing primary angioplasty. METHODS AND RESULTS: In 118 consecutive patients with AMI undergoing successful reperfusion (TIMI 2 and 3) by primary angioplasty, plasma concentrations of norepinephrine, epinephrine and N-terminal proBNP (NT-proBNP) were measured before, 60 min and 10 days after angioplasty. Catecholamine concentrations (mean+/-SEM) rose to a maximum in the first hour after angioplasty (norepinephrine: 602+/-44 ng/L, epinephrine: 213+/-24 ng/L) and returned to normal at day 10. Conversely, NT-proBNP levels maintained a further increase from 799+/-44 pmol/L at baseline to 924+/-54 pmol/L at day 10. A NT-proBNP concentration above median at 60 min post-angioplasty predicted major adverse cardiac events (n=27) during the 18-36 month follow-up with an odds ratio of 5.9 (1.7-20.3) and was superior to catecholamines, to left ventricular ejection fraction and to other established postinfarction risk markers. CONCLUSIONS: In a low-risk cohort of patients with AMI undergoing successful reperfusion therapy, plasma NT-proBNP concentrations are elevated for at least ten days. The prognostic value of early plasma NT-proBNP should be further evaluated concerning its ability to facilitate risk stratification of infarct patients.

Aged↗

Diagnostic and prognostic role of myoglobin in patients with suspected acute coronary syndrome. North-Württemberg Infarction Study (NOWIS) Group.

In patients with suspected acute coronary syndrome, myoglobin is, according to IFCC and NACB guidelines, the marker of choice for early determination of acute infarction, in particular in combination with creatine kinase-MB, 4 hours after admission with a sensitivity of 96%, and correctly excludes Q-wave infarctions. In patients without acute myocardial infarction, a positive troponin T (relative risk 31.5%), but not an elevated myoglobin (relative risk 4.5%), is highly predictive for adverse in-hospital outcome.

Angina, Unstable↗

Dilated cardiomyopathy and sensorineural hearing loss: a heritable syndrome that maps to 6q23-24.

BACKGROUND: Dilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized. METHODS AND RESULTS: Clinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. Polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292, a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified. CONCLUSIONS: A syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart.

Adult↗

Carvedilol for prevention of restenosis after directional coronary atherectomy : final results of the European carvedilol atherectomy restenosis (EUROCARE) trial.

BACKGROUND: In addition to its known properties as a competitive, nonselective beta and alpha-1 receptor blocker, carvedilol directly inhibits vascular myocyte migration and proliferation and exerts antioxidant effects that are considerably greater than those of vitamin E or probucol. This provides the basis for an evaluation of carvedilol for the prevention of coronary restenosis. METHODS AND RESULTS: In a prospective, double-blind, randomized, placebo-controlled trial, 25 mg of carvedilol was given twice daily, starting 24 hours before scheduled directional coronary atherectomy and continuing for 5 months after a successful procedure. The primary end point was the minimal luminal diameter as determined during follow-up angiography 26+/-2 weeks after the procedure. Of 406 randomized patients, 377 underwent attempted atherectomy, and in 324 (88.9%), a </=50% diameter stenosis was achieved without the use of a stent. Evaluable follow-up angiography was available in 292 eligible patients (90%). No differences in minimal luminal diameter (1.99+/-0.73 mm versus 2.00+/-0.74 mm), angiographic restenosis rate (23.4% versus 23.9%), target lesion revascularization (16.2 versus 14.5), or event-free survival (79.2% versus 79.7%) between the placebo and carvedilol groups were observed at 7 months. CONCLUSIONS: The maximum recommended daily dose of the antioxidant and beta-blocker carvedilol failed to reduce restenosis after successful atherectomy. These findings are in contrast to those of the Multivitamins and Probucol Trial, which raises doubts regarding the validity of the interpretation that restenosis reduction by probucol was via antioxidant effects. The relationship between antioxidant agents and restenosis remains to be elucidated.

Adrenergic Antagonists↗

Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins.

Catheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication defective adenovirus within the targeted myocardium. Adenoviral vectors consisted either of luciferase (Ad.rsv-Luc) or beta-galactosidase (Ad.rsv-betaGal) reporter gene under control of an unspecific promotor derived from the Rous sarcoma virus (RSV). In this pig model, selective retrograde gene delivery into the anterior cardiac vein during a brief period of ischemia substantially increased reporter gene expression in the targeted myocardium (LAD region) compared with antegrade delivery as a control. Repeated retrograde delivery during two periods of brief ischemia resulted in a more homogeneous transmural expression predominantly observed in cardiomyocytes (X-gal-staining). In the nontargeted myocardium (CX region) there was no evidence for adenoviral transfection. From our data we infer that selective pressure-regulated retroinfusion is a promising approach for efficient percutaneous transluminal gene delivery to the myocardium. Gene Therapy (2000) 7, 232-240.

Adenoviridae↗

Clinical and Angiographic Results with the Multi-Linkª Coronary Stent System Ñ The West European Stent Trial (WEST).

BACKGROUND: The objectives for the West European Stent Trial (WEST) were to assess the safety and efficacy of the new ACS Multi-Linkª coronary stent system with regards to bleedings and vascular complications and incidence of major adverse cardiac events during 12 months follow-up. METHODS AND RESULTS: The balloon-expandable Multi-Link stent is made from a single hypotube and is composed of 316 L stainless steel. In an open, non-randomized, multicenter registry, 102 patients with angina pectoris to be treated with this stent were recruited from 7 European centers. Following stent implantation, patients were given heparin infusion and oral coumadin treatment was maintained for 3 months. Procedural success was achieved in 100 of the 102 patients (98%). One patient had subacute stent thrombosis and 6 patients had major bleeds during the hospital stay. All patients were alive at 12 months and 85% were free of angina pectoris. Nineteen patients (19%) reached a primary clinical endpoint; four patients underwent bypass surgery (two in connection with the stent procedure), four patients suffered an acute myocardial infarction and 11 had a repeat angioplasty of the target vessel. Quantitative angiography showed that the minimum lumen diameter had decreased from 2.66 +/- 0.34 mm after stent deployment to 2.02 +/- 0.58 mm at 6 months and the percent diameter stenosis had increased from 18 +/- 7% to 33 +/- 16%. The in-stent restenosis rate was 12% and appearance of a stenosis in the target vessel outside the stent occurred in an additional 5%. CONCLUSION: The WEST study has demonstrated a high degree of safety and efficacy of the Multi-Link stent with a low incidence of complications and clinical events during follow-up. The results compare favorably with data from other stents.

Journal Article↗

Clinical and Angiographic Results with the Multi-Linkª Coronary Stent System Ñ The West European Stent Trial (WEST).

BACKGROUND: The objectives for the West European Stent Trial (WEST) were to assess the safety and efficacy of the new ACS Multi-Linkª coronary stent system with regards to bleedings and vascular complications and incidence of major adverse cardiac events during 12 months follow-up. METHODS AND RESULTS: The balloon-expandable Multi-Link stent is made from a single hypotube and is composed of 316 L stainless steel. In an open, non-randomized, multicenter registry, 102 patients with angina pectoris to be treated with this stent were recruited from 7 European centers. Following stent implantation, patients were given heparin infusion and oral coumadin treatment was maintained for 3 months. Procedural success was achieved in 100 of the 102 patients (98%). One patient had subacute stent thrombosis and 6 patients had major bleeds during the hospital stay. All patients were alive at 12 months and 85% were free of angina pectoris. Nineteen patients (19%) reached a primary clinical endpoint; four patients underwent bypass surgery (two in connection with the stent procedure), four patients suffered an acute myocardial infarction and 11 had a repeat angioplasty of the target vessel. Quantitative angiography showed that the minimum lumen diameter had decreased from 2.66 +/- 0.34 mm after stent deployment to 2.02 +/- 0.58 mm at 6 months and the percent diameter stenosis had increased from 18 +/- 7% to 33 +/- 16%. The in-stent restenosis rate was 12% and appearance of a stenosis in the target vessel outside the stent occurred in an additional 5%. CONCLUSION: The WEST study has demonstrated a high degree of safety and efficacy of the Multi-Link stent with a low incidence of complications and clinical events during follow-up. The results compare favorably with data from other stents.

Journal Article↗

Refractory oedema in congestive heart failure: a contributory role of loop diuretics?

We report a patient with congestive heart failure (CHF) who presented with massive oedema resistant to therapy with maximal doses of loop diuretics, despite an adequate renal function. After a diuretic pause and dietary salt restriction, a conventional dose of furosemide in combination with distally active diuretics induced a prompt weight loss exceeding 30 kg with stable renal function. We suggest that the 'refractory' oedema in this patient was due to a combination of CHF and inappropriate (loop) diuretic therapy in conjunction with a high dietary sodium intake. We conclude that in the absence of hyponatremia and renal failure, even severe oedema may not represent a negative prognostic indicator. The recognition of diuretic-associated mechanisms complicating cardiac oedema is essential to avoid the vicious circle of worsening oedema whilst escalating therapy with loop diuretics.

Adult↗

Cardiac troponin I and tension generation of skinned fibres in the developing rat heart.

During development of the myocardium the troponin I (TNI) isoform expression is switched from a cAMP-insensitive, slow skeletal muscle TNI to a cAMP-sensitive, cardiac TNI isoform (cTNI). To study the functional consequence of alterations in cTNI expression in the rat heart we investigated the cAMP-controlled cTNI phosphorylation in comparison with alterations of functional properties of isolated cardiac myofibrils during the first postnatal month. cTNI was identified by Western blot analysis followed by a semiquantitative assessment. From the third to the 28th postnatal day the relative concentrations of the cardiac isoform of TNI increased 2.9 +/- 0.3-fold. In the same period the amount of phosphate incorporated into cTNI in the presence of exogenous cAMP-dependent protein kinase (PKA) and 32P[gamma]-ATP was increased 5.8 +/- 0.2-fold (24.2 +/- 3.5 v 140.2 +/- 7.6 pmolP/mg protein loaded onto the gel) whereas the phosphorylation of C-protein was only increased 1.6 +/- 0.2-fold. Ca(2+)-activated isometric tension generation of skinned heart fibres measured in the range of pCa from 6 to 4.5 was not affected by PKA at day 3. However, isometric tension generation of fibres prepared from 28-day-old rats was suppressed by incubation with PKA which was accompanied by a rightward shift in the force/pCa relation. Under these conditions half-maximal tension development was found at pCa 5.38 v 5.52 (p < 0.05) in the absence of PKA. The Ca2+ sensitivity of the contractile apparatus was not affected by PKA-induced phosphorylation of C-protein. These data give direct evidence for the physiological relevance of the onset of cAMP-induced phosphorylation of cTNI for the Ca(2+)-activated tension generation in cardiac myofibrils during postnatal development.

Animals↗

Release of chemoattractants and neutrophil activation in acute myocardial infarction immediately after successful recanalization of the infarct-related vessel by angioplasty.

The study investigated inflammatory responses in evolving myocardial infarction. Fifteen patients with acute myocardial infarction, who had undergone balloon recanalization of the infarct-related coronary artery within 4 h after onset of symptoms, were examined. Blood samples were obtained through the guiding catheter and from the pulmonary artery before and immediately after successful recanalization. After recanalization, plasma from the pulmonary artery was 47% (quartiles: 19%, 78%; P = 0.001) more chemotactic to neutrophils from normal donors than before recanalization. Furthermore, significant changes in neutrophil function were found in the pulmonary artery. Compared to the values before recanalization, the nitroblue tetrazolium score rose by 31% (quartiles: 4%, 37%; P = 0.003), FMLP-stimulated superoxide anion production by 10% (quartiles: 0%, 39%; P = 0.020), and chemotaxis by 46% (quartiles: 0%, 81%; P = 0.011), while neutrophil filterability decreased by 28% (quartiles: 15%, 47%; P = 0.010). No significant changes in neutrophil parameters were found in the arterial blood. The study indicates that chemoattractants are released in the early reperfusion period of evolving myocardial infarction. These chemoattractants may act as inflammatory mediators causing neutrophil activation.

Aged↗

S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB.

In a multicenter study we compared three tests for ischemic myocardial injury (IMI): a new, automated enzyme immunoassay for S-troponin T (S-TNT; Boehringer Mannheim) and two S-creatine kinase (CK) isoenzyme MB assays (mass and catalytic concentrations). For critical evaluation of clinical sensitivity, we studied 243 cases with an IMI prevalence of 43% and an 18% prevalence of cases with unstable angina. Relative peak values of S-TNT and S-CK-MB (mass) after onset of pain were four- to fivefold higher than S-CK-MB (catalytic) results. Increases of S-TNT and S-CK-MB (mass), even though still within their reference ranges, indicated minor myocardial damage in about one-third of the cases primarily classified as unstable angina. The diagnostic window for S-TNT ranged from hours to weeks after the acute episode. The time courses were frequently biphasic, with the initial S-TNT peak closely paralleling that of the mass concentrations of S-CK-MB. With a biological half-life for S-TNT of 2 h, the prolonged increases in S-TNT indicate a continuous release of S-TNT from necrotizing cells. Clinical specificities of S-TNT and S-CK-MB (mass) were greater than that of S-CK-MB (catalytic), even in the presence of 30% to 40% severe skeletal muscle injuries. The combination of S-TNT and S-CK-MB (mass) is excellent for detection of acute IMI, including minor myocardial damage.

Catalysis↗

[Percutaneous transfemoral valvuloplasty in patients with calcified aortic stenosis and significantly increased surgical risk: clinical course and value of Doppler sonography in assessment of therapeutic success].

Percutaneous transluminal valvuloplasty (PTV) was performed in 24 patients (aged 67-86 years, mean: 76 +/- 5.7 years) with calcific aortic stenosis and high operative risk. The gradient between maximal left ventricular and aortic pressures (peak-to-peak gradient, PPPG) could be reduced by 52% from 73 +/- 21 to 34 +/- 12 mmHg (p less than 0.001). Peak pressure gradient (PPG), as assessed by continuous wave Doppler, could be reduced from 80 +/- 28 to 58 +/- 21 mmHg (p less than 0.001). Aortic valve area (AVA) as determined by Doppler and two dimensional echocardiography increased significantly from 0.39 +/- 0.14 to 0.61 +/- 0.3 cm2 (p less than 0.05). Clinical symptoms were found to be improved in 5 of 8 patients with impaired ejection fraction and in 11 of 16 patients with normal ejection fraction during the first week after PTV. Complications due to the procedure were surgical revision of femoral artery puncture site in one patient and hemodynamic relevant pericardial effusion in another patient. Transmitral early (E) and late (L) diastolic filling integrals were measured by pulsed Doppler: the ratio E/L decreased significantly after PTV from 0.9 +/- 0.5 to 0.63 +/- 0.31 (p less than 0.03) indicating further reduction of left ventricular early diastolic filling. Ejection fraction, stroke volume and cardiac output did not significantly change immediately after PTV.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

sn-1,2-Diacylglycerols and phorbol diesters stimulate thromboxane synthesis by de novo synthesis of prostaglandin H synthase in human promyelocytic leukemia cells.

We studied the regulation of thromboxane (TX) synthesis in promyelocytic leukemia cells during macrophage differentiation. Cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) showed rates of TXB2 synthesis from exogenous arachidonic acid that exceeded that of control cells by a factor of up to 81. Cells treated with sn-1,2-dioctanoylglycerol (diC8) showed similarly high TXB2 synthesis rates when diC8 was added concomitantly with a subthreshold concentration of TPA or when given in multiple doses. These activities depended on de novo synthesis of prostaglandin H (PGH) synthase because: microsomal PGH synthase activity showed large increases in Vmax values, and mass measurements of PGH synthase revealed the presence of PGH synthase in differentiating cells whereas the enzyme was undetectable in control cells. These results indicate that macrophage differentiation is associated with stimulation of TXB2 synthesis that requires both activation of protein kinase C and de novo synthesis of PGH synthase.

Arachidonic Acid↗

Myocardial hypertrophy in rats with renal insufficiency.

Increased defatted dry wt of the heart and increased heart calcium content were observed in subtotally nephrectomized male Sprague-Dawley rats compared with sham-operated pairfed controls. Increased heart wt contrasted with no change of the weight of viscera (liver, spleen) and markedly decreased weight of striated muscle. Heart wt was unchanged after 5 days of renal insufficiency, but significantly increased after 14 or 21 days. Increased heart wt persisted despite effective beta adrenoreceptor blockade (2 X 10 mg metroprolol/kg/day i.p.) or effective alpha-1-adrenoreceptor blockade (2 X 2 mg prazosin/kg/day i.p.). Increased heart wt was also demonstrable despite normalization of basal blood pressure (intraarterial blood pressure measurement in conscious animals): blood pressure was lowered in one series with hydralazine/nadolol in drinking water (calculated to deliver 20 and 2 mg/kg/day, respectively) and in another series with furosemide in drinking water (15 mg/kg/day) combined with metoprolol (2 X 10 mg/kg/day i.p.). Increased heart wt was also noted despite correction of anemia by blood transfusion (Hct greater than 40%) and after parathyroidectomy in animals kept eucalcemic with high dietary calcium. Micromorphometry of left ventricular myocardium in perfusion-fixed tissue showed no significant change of the relative proportion of connective tissue and myocardial fibers. Myocardial isomyosin pattern was changed with an increase of fast-migrating V1 isomyosin in animals with renal insufficiency compared to sham-operated pairfed controls.

Adenosine Triphosphatases↗

Intracoronary thrombolysis in acute myocardial infarction: an attempt to quantitate its effect by comparison of enzymatic estimate of myocardial necrosis with left ventricular ejection fraction.

The quantity of myocardium was estimated that can be salvaged by reperfusion of acute transmural myocardial infarction (MI). Serial analysis of serum creatine kinase (CK) activity was carried out in 41 consecutive patients with acute MI who underwent intracoronary thrombolysis. Enzymatic estimate of MI size was calculated using an average (method A) and an individually determined elimination constant (method B). Left ventricular ejection fraction 4 weeks after successful thrombolysis (cineangiogram) correlated inversely with MI size (method A: r = -0.85, method B: r = -0.76; both p less than 0.001). Patients with recanalization within 4 hours after the onset of symptoms were assembled in group A1 (n = 13, early reperfusion), and patients with successful recanalization after 4 hours in group A2 (n = 16, late reperfusion). Group B consisted of 12 patients without reperfusion. MI size in group A1 was 21 CK-g-Eq (method A) and 23 CK-g-Eq (method B), in group A2 50 CK-g-Eq (method A) and 54 CK-g-Eq (method B), and in group B 73 CK-g-Eq (method A) and 63 CK-g-Eq (method B). Mean values in group A1 were lower than in group A2 and group B (p less than 0.05). It is concluded that MI size was significantly reduced to about one third after early reperfusion as compared with no reperfusion. In contrast, MI size was not significantly reduced after late reperfusion.

Adult↗