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G Breithardt

Publications and source records attributed to G Breithardt.

At least 91 records · Page 5Linked to original sources
PubMed2000

Effects of antiarrhythmic drugs on cloned cardiac voltage-gated potassium channels expressed in Xenopus oocytes.

The effects of 17 commonly used antiarrhythmic drugs on the rapidly activating cardiac voltage-gated potassium channels (Kv1.1, Kv1.2, Kv1.4, Kv1.5, Kv2.1 and Kv4.2) were studied in the expression system of the Xenopus oocyte. A systematic overview on basic properties was obtained using a simple and restricted experimental protocol (command potentials 10 mV and 50 mV positive to the threshold potential; concentration of 100 micromol/l each). The study revealed that 8 of 17 drugs yielded significant effects (changes >10% of control) on at least one type of potassium channel in the oocyte expression system. These drugs were ajmaline, diltiazem, flecainide, phenytoin, propafenone, propranolol, quinidine and verapamil, whereas the effects of adenosine, amiodarone, bretylium, disopyramide, lidocaine, mexiletine, procainamide, sotalol and tocainide were negligible. The drug effects were characterized by reductions of the potassium currents (except for quinidine and ajmaline). A voltage-dependence of drug effect was found for quinidine, verapamil and diltiazem. The different effect of the drugs was not related to the fast or slow current inactivation of the potassium channels (except for verapamil). Profiles of the individual drug effects at the different potassium channel types were identical for propafenone and flecainide and differed for all other substances. The study demonstrates marked differences in sensitivity to antiarrhythmic drugs within the group of voltage-operated cardiac potassium channel types. Taking the restrictions of the oocyte system into consideration, the findings suggest that several antiarrhythmic drugs exert significant effects at rapidly activating cardiac potassium channels.

Animals↗
PubMed2000

Clinical evaluation of no-carrier-added meta-[123I]iodobenzylguanidine for myocardial scintigraphy.

In clinical and research studies, images obtained using carrier-added meta-[123I]iodobenzylguanidine (c.a. [123I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [123I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [123I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [123I]MIBG. Twelve of the 24 patients were studied with c.a. [123I]MIBG (seven females and five males; mean age 42+/-13 years, range 20-60 years), whereas the other 12 were studied with n.c.a. [123I]MIBG (ten females, two males; mean age 41+/-11 years, range 18-60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [123I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3+/-3.2 vs 5.3+/-1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5+/-0.6 vs 1.5+/-0.3, P=0.0002, and 0.8+/-0.2 vs 0.6+/-0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2+/-1.3 vs 3.6+/-1.1, P=0.39, and 13.7+/-5.2 vs 9.6+/-2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [123I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [123I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended.

3-Iodobenzylguanidine↗
PubMed2000

[New knowledge in arrhythmogenesis--role of ion channels and genetic aspects].

Recent advances in molecular biology have had a major impact on our understanding of the mechanisms of human diseases. Electrophysiology is one of the areas which, besides others, has substantially benefited from this development. Our understanding of the structure, function and mechanisms of the regulation of ion channels as well as their contribution to the pathogenesis of cardiac arrhythmias has substantially increased. The results of these studies are not only of special interest from the scientific point of view. It is likely to assume that, in the future, they will increasingly influence the diagnosis and treatment of arrhythmias.

Arrhythmias, Cardiac↗
PubMed2000

Molecular genetics of arrhythmias--a new paradigm.

The molecular genetic background of inherited cardiac arrhythmias has only recently been uncovered. This late development in comparison to other inherited cardiac disorders has partly been due to the high mortality and early disease onset of these arrhythmias resulting in mostly small nucleus families. Thus, traditional genetic linkage studies, which are based on the genetic information obtained from large multi-generation families, were made difficult. Inherited arrhythmogenic disorders can be divided into 'primary electrical disorders' (e.g., long-QT [LQT] syndrome) in which a detectable, organic heart disease is not evident, and into inherited diseases of the myocardial structure (e.g., hypertrophic cardiomyopathies) in which the arrhythmias occur combined with the structural alterations. To date, all inherited arrhythmogenic disorders in which the causative genes have been identified turned out to be channelopathies, since the genes encode channel subunits that regulate important ion currents that tune the cardiac action potential. The discovery of the genetic bases of the LQT syndrome became a new methodologic paradigm; because with the use of 'classical' genetic linkage strategies (named [positional] candidate strategies) not only the causative genes have been found, but moreover, functional components with a previously unknown but fundamental role for a normal repolarization process were discovered. Disease mutations turned out to be not only a family-specific event with a distinct phenotype and the potential of an additional diagnostic tool, but also, when expressed in heterologous expression systems, characterize the defective ion channel in a topological way and lead to a more specific understanding of ion channel function. Most, if not all, primary electrical cardiac disorders show a high genetic diversity. For the LQT syndromes, sixth disease loci and the responsible gene have been recently discovered (so-called locus or genetic heterogeneity). Within all disease genes, the mutations are spread over the entire gene (allelic heterogeneity); in addition, more than one disease mutation may be present. This complexity requires, at least, complete mutation analysis of all LQT genes before medical advice should be given. Meanwhile, genotype-phenotype correlations in large families are being used to evaluate intergene, interfamilial and intrafamilial differences in the clinical phenotype, reflecting gene specific, gene-site specific and individual consequences of a given mutation. A widespread phenotypic heterogeneity even within mutation carriers in the same family raises the importance of modifying factors and genes that are mostly unknown to date. The reduced penetrance and variable expressivity associated with the LQT mutations remain still to be explained. First insights into the complex actions of mutations are being extracted, from expression data; these preliminary results may lead to potential implications for a specific (gene-site directed) therapy. This paper discusses the current data on molecular genetics and genotype-phenotype correlations in LQT syndrome and related disorders and the potential implications for diagnosis and treatment.

Arrhythmias, Cardiac↗
PubMed2000

Emergency coronary artery bypass grafting after failed coronary angioplasty: what has changed in a decade?

BACKGROUND: We assessed the impact of patient and procedural characteristics on the outcome after emergency coronary artery bypass grafting (CABG) for failed percutaneous transluminal coronary angioplasty (PTCA) and temporal changes in these factors. METHODS: Patients who underwent PTCA and subsequent emergency CABG were identified from the databases of the Departments of Cardiology and Cardiothoracic Surgery. RESULTS: Two periods of clinical practice were compared. In 1989 to 1993, 2,880 PTCAs were performed, 64 patients underwent emergency CABG (2.3%), and 7 patients died (10.9%). During 1994 to 1998, 46 patients of 3,801 PTCAs underwent emergency CABG (1.2%, p < 0.01), and 7 patients died (15.2%, NS). The average rate of stenting increased from 0.8% to 24% in 1994 to 1998 as well as the frequency of arterial bypass grafts (0% vs 39%). In the latter period, patients were older, were more often females, had more cardiovascular risk factors, a higher Cleveland score (each p < 0.05), and suffered more often from periprocedural myocardial infarctions (p < 0.001) and nonfatal periprocedural complications (p < 0.01). CONCLUSIONS: Although the frequency of emergency CABG after failed PTCA declined, perioperative mortality tended to increase according to an unfavorable shift in patient risk factors and morbidity.

Adult↗
PubMed2000

Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography.

Coronary events have a close association with a low HDL/hypertriglyceridemia (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipoproteins are associated with a modulation of both HDL cholesterol and triglycerides, we have tested the hypothesis that mutations in the genes encoding lipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the formation of coronary atherosclerosis and, thus, of coronary heart disease (CHD). The entire coding and boundary regions of LPL and HTGL genes were analyzed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD. In the LPL gene six different polymorphisms were identified with same frequencies observed in the general population. In the HTGL gene, besides several polymorphisms, we identified three missense mutations: Asn37His, Val73Met, and Ser267Phe. Population screening using allele specific PCR identified Val73Met as a polymorphism while the two others were absent from 100 control individuals. One of the mutations (Ser267Phe) is known to cause HTGL deficiency and is associated with type III hyperlipoproteinemia. Since this dyslipoproteinemia meets the criteria of LHDL/HTG, it is intriguing to speculate that missense mutations in HTGL may play a role in the pathogenesis of this atherogenic phenotype.

Adult↗
PubMed2000

Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture.

We investigated the influence of lovastatin, simvastatin and pravastatin on proliferation and viability of vascular smooth muscle cells (SMC) in vitro and studied the effects of lovastatin on a mouse SMC line transgenic for a temperature-sensitive mutant of SV40 large T antigen (TAg), known to inhibit the function of p53 and pRb family members. We found that lovastatin and simvastatin inhibited cell proliferation by provoking G0/G1 phase arrest with concomitant depression of the proliferation antigen Ki-67/MIB-1. Lovastatin at high concentrations of 20 micromol/l caused cell death in the presence of serum but not under serum starved conditions, which was verified on the basis of increased DNA strand breaks, decreased DNA content and morphological alterations seen by electron microscopy. Cell death was also found for simvastatin, whereas pravastatin did not exhibit antiproliferative or cytotoxic effects. Mouse SMC transgenic for TAg did not show any impaired sensitivity to the antiproliferative and cell death inducing effect of lovastatin, but both effects could be antagonized by the supplementation of mevalonate. The data indicate that antiproliferative and cytotoxic effects of lovastatin are caused by the using up of products of mevalonate metabolism and do not require the presence of p53 or pRb.

Animals↗
PubMed2000

Clusters of ventricular tachycardias signify impaired survival in patients with idiopathic dilated cardiomyopathy and implantable cardioverter defibrillators.

OBJECTIVES: This retrospective study was undertaken to provide data on occurrence, significance and therapy of ventricular tachyarrhythmia (VT) clusters (VTCs) in patients with dilated cardiomyopathy (DCM) and implantable cardioverter defibrillators (ICDs). BACKGROUND: Data on the clinical significance of VTCs are lacking in patients with DCM and ICDs. METHODS: Baseline characteristics of 106 consecutive patients with DCM and ICDs were prospectively collected, and chart reviews and episode data retrospectively analyzed. A VTC was defined as > or =3 sustained VTs/24 h. RESULTS: During a mean follow-up of 33+/-23 months, 73 patients (68.9%) had recurrent VT or ventricular fibrillation (VF), 43 patients (40.6%) suffered only single VTs and 30 patients (28.3%) experienced 52 clusters of VTs. Actuarial survival free of VT or VF was 44.6%, 33.0% and 26.5%, and survival free of VTC was 77.3%, 72.2% and 67.1% after one, two and three years, respectively. Independent predictors of VT clusters were heart failure before ICD implantation (p = 0.033), presenting monomorphic VT (p = 0.044), EF <0.40 (p = 0.014) and inducible mVT, especially with right bundle branch block and superior axis configuration (p<0.001). Survival free of recurrent VTCs was 50.8%, 38.1% and 19.0% after one, two and three years, respectively. Once a VTC had occurred, only 56.7%, 46.4%, 30.9% and 15.5% of patients survived and were not transplanted after one, two, three and four years, respectively. Survival was even more reduced if a VTC was associated with cardiac decompensation: 65.6% and 21.9% after one and two years, respectively. CONCLUSIONS: Despite antiarrhythmic intervention, clusters of VTs occur and recur frequently in patients with DCM. They signify impaired survival, especially if they are associated with cardiac decompensation, and may be a harbinger of progressive myocardial deterioration rather than a primarily arrhythmic problem. The benefit of ICD therapy may therefore be low in these patients.

Aged↗
PubMed2000

Ventricular tachycardias above the initially programmed tachycardia detection interval in patients with implantable cardioverter-defibrillators: incidence, prediction and significance.

OBJECTIVES: This retrospective study was performed to provide data on ventricular tachycardias (VT) with a cycle length longer than the initially programmed tachycardia detection interval (TDI) in patients with implantable cardioverter defibrillators (ICDs). BACKGROUND: It has been clinical practice to program a safety margin of 30 to 60 ms between the slowest spontaneous or inducible VT and the TDI. METHODS: Baseline characteristics of 659 consecutive patients with ICDs were prospectively; follow-up information was retrospectively collected. RESULTS: During a mean follow-up of 31+/-23 months, 377 patients (57.2%) had at least one recurrent VT or ventricular fibrillation; 47 patients (7.1%) suffered 61 VTs above the TDI. The risk of a VT above the TDI ranged between 2.7% and 3.5% per year during the first four years after ICD implantation. The difference between the cycle length of the slowest VT before ICD implantation, spontaneous or induced, and the first VT above TDI was 108+/-58 ms. Fifty-four VTs (88.5%) above the TDI were associated with significant clinical symptoms (angina or palpitation 63.9%, heart failure 6.6% and syncope 8.2%). Six patients (9.8%) had to be resuscitated. Kaplan-Meyer analysis identified New York Heart Association class II or III (p = 0.021), ejection fraction < 0.40 (p = 0.027), spontaneous (p<0.001) or inducible (p<0.001) monomorphic VTs and the use of class III antiarrhythmic drugs (amiodarone, p<0.001; sotalol, p = 0.004) as risk predictors of VTs above the TDI. The risk of recurrent VTs above TDI was 11.8%, 12.5% and 26.6% during the first, second and third year after first VT above TDI, respectively. CONCLUSIONS: The risk of VTs above the TDI is significantly increased in some patients, and many VTs above TDI cause significant clinical symptoms. A larger safety margin between spontaneous or inducible VTs and the TDI seems to be necessary in selected patients. This is in conflict with an increased risk of inadequate episodes and demands highly specific and sensitive detection algorithms in these patients.

Defibrillators, Implantable↗
PubMed2000

Selection and management of ventricular assist device patients: the Muenster experience.

BACKGROUND: Because of the growing discrepancy between the availability of donor organs and the number of patients with end-stage heart disease who need heart transplantation, a larger proportion of patients waiting for a suitable donor heart require pre-operative mechanical circulatory assistance. The criteria for the selection and management of these patients as applied at Muenster University Hospital are reviewed. METHODS: The study population consists of 631 patients referred to our center for transplantation between January 1, 1990, and December 31, 1996. Two hundred ninety-seven patients were listed for transplantation and 157 were transplanted. Of 41 patients who underwent implantation of a ventricular assist device (n = 34, Novacor; n = 6, TCI HeartMate; n = 1, Medos), 39 received the device as a bridge to transplantation and 2 as permanent support. For the purpose of the analysis, the study population was divided into 3 groups (elective bridging, urgent bridging, emergency bridging) and compared with heart transplant candidates who did not require mechanical circulatory assistance. RESULTS: Patients who underwent elective or urgent assist-device implantation were younger and had greater hemodynamic compromise than the remainder of patients waiting for heart transplantation, as suggested by a higher functional class and lower mean arterial pressure, cardiac index, serum sodium, and pulmonary artery wedge pressure. Survival of patients who electively underwent implantation of an assist device was better than that of patients who were stable on the waiting list and did not undergo heart transplantation during follow-up. CONCLUSIONS: This finding suggests that earlier implantation of assist devices may facilitate resolution of organ dysfunction before heart transplantation.

Adult↗
PubMed2000

Is there a need for routine testing of ICD defibrillation capacity? Results from more than 1000 studies.

AIMS: Benefits and complications of postoperative implantable cardioverter-defibrillator tests are controversial matters. This study sought to assess the necessity of defibrillation function tests after implantation. METHODS AND RESULTS: We retrospectively analysed 1007 implantable cardioverter-defibrillator tests in 587 systems and 556 patients. Nine hundred and thirty implantable cardioverter-defibrillator tests (89.4%) were routinely performed. Seventy-one tests (7%) were performed after a change in the antiarrhythmic drug regimen and six tests (0.60%) because of a suspected dysfunction of the implantable cardioverter-defibrillator. During routine tests, four systems (0.4%) failed to defibrillate the patient. However, in all but one test, abnormalities of the system had been observed before the test. After the addition of antiarrhythmic drugs, two of 71 implantable cardioverter-defibrillator systems (2.8%) failed to defibrillate the patient. One of six systems tested due to a suspected dysfunction failed to defibrillate the patient. During 16 tests (1.6%), complications occurred. CONCLUSIONS: Our experience demonstrates that postoperative tests of the defibrillation function of implantable cardioverter-defibrillators rarely reveal dysfunctions. As testing is unpleasant for the patient and not free of complications, tests might be restricted to those patients in whom a dysfunction is suspected and to those patients in whom class I or class III antiarrhythmic drugs have been added to the antiarrhythmic drug regimen.

Adolescent↗
PubMed2000

Prevalence of coronary artery disease in a general population without suspicion of coronary artery disease: angiographic analysis of subjects aged 40 to 70 years referred for catheter ablation therapy.

BACKGROUND: The prevalence of coronary vessel wall alterations in the general population is not known. Therefore, the aim of our study was to determine the prevalence of coronary artery disease in persons in whom the underlying disease was not related to coronary artery disease and could therefore be regarded as a near normal population. METHODS: We included 331 consecutive patients (173 men, 158 women, aged between 40 and 70 years) who were referred for catheter ablation of an accessory pathway (67.4% ) or atrioventricular-node modification (32.6%) and who underwent coronary angiography as part of their routine baseline evaluation before radiofrequency current application. Most of the patients (79%) of this cohort were free of symptoms of coronary artery disease. Based on visual inspection of coronary angiograms in multiple projections, patients were classified to have one-, two- or three-vessel disease if stenoses greater than 50% of lumen diameter were present. In addition, diffuse vessel wall alterations were assessed using two different score systems. RESULTS: The prevalence of coronary artery disease in this near normal population was 7.3%, with a significant difference in coronary asymptomatic (3.8%) vs symptomatic patients (17.1%). Mean levels of total cholesterol and other risk factors were not significantly different in patients with coronary artery disease compared to those without. But levels of low-density lipoprotein (LDL) cholesterol and lipoprotein(a) were significantly higher and high-density (HDL) cholesterol lower in patients with a stenosis or extent score higher than zero compared to a score of zero. The values of all vessel scores evaluating the extent of critical and diffuse coronary vessel alterations were very low in patients affected with coronary artery disease, indicating a low degree of diffuse alteration of the vessel wall. CONCLUSIONS: The prevalence of coronary artery disease with at least one critical stenosis in subjects aged 40-70 years with an average cholesterol level of 238+/-42 mg. dl(-1)is 7.3%.

Arrhythmias, Cardiac↗
PubMed2000

Fractally coated defibrillation electrodes: is an improvement in defibrillation threshold possible?

AIMS: In patients with implantable cardioverter-defibrillators (ICD), the goals of lowering the defibrillation threshold (DFT) can be achieved by means of higher defibrillation safety margins, more rapid charging of capacitors, improved battery longevity, implying smaller devices. Whether an increase in the electrically active surface of ICD leads by fractal coating results in decreased DFTs is unknown. METHODS AND RESULTS: In this prospective randomized cross-over study the defibrillation efficacy of a novel right ventricular endocardial defibrillation electrode fractally coated with iridium was compared with an uncoated but otherwise identical electrode in 30 patients undergoing ICD implantation. In each patient, DFT testing was performed twice according to a binary search protocol introducing the two different electrodes in a random order. The mean DFT was 8.4 +/- 4.1 J with the fractally coated lead and 9.6 +/- 3.6 J using the uncoated lead. The improvement of 1.2 J was statistically not significant (P = 0.11). No differences were observed between the patients with an improved DFT (n =12) and those with an unchanged or worsened DFT (n = 18) concerning age, underlying cardiac disease, NYHA class, or left ventricular ejection fraction, respectively. CONCLUSION: Increasing the electrical surface of defibrillation leads by fractal coating does not lead to a substantial clinically relevant reduction in defibrillation thresholds. Defibrillation impedance is not influenced by the increased electrical surface of the defibrillation lead.

Adult↗
PubMed2000

Modification of stretch-induced shortening of repolarization by streptomycin in the isolated rabbit heart.

The exact mechanism of mechano-electrical feedback and stretch-induced arrhythmias is unknown, but the role of stretch-activated ion channels and specific calcium channels has been proposed. The aim of the present study was to test the hypothesis that stretch-activated ion channels and not calcium channels contribute to stretch-related alterations of repolarization and that these effects can be neutralized by stretch-activated channel block. We studied the interaction of acute ventricular dilatation and the stretch-activated channel blocker streptomycin and the specific calcium channel blocker verapamil in an isolated retrogradely perfused rabbit heart model in which the left ventricular size is modified by abruptly changing the volume of a fluid-filled balloon placed in the left ventricle. Acute ventricular dilatation led to a rate-dependent decrease in repolarization. The mean effective refractory period (ERP) and monophasic action potential duration (MAP90) for cycle lengths between 300 and 1,000 ms decreased from 174.2+/-9 ms and 178.9+/-7 ms to 161.6+/-11 ms and 169.7+/-5 ms, respectively. Streptomycin (80 microM) inhibited this stretch-related shortening of repolarization (ERP: 175.4+/-8 ms; MAP90: 179.7+/-8 ms, p < 0.05) but had almost no effect on already dilated ventricles. Counteraction of the observed electrophysiologic changes could only be achieved by increasing the streptomycin concentration to 200 microM. Streptomycin nearly completely suppressed stretch-related ectopic ventricular complexes. In contrast, verapamil (1 microM) had no effect on stretch-related changes in repolarization and stretch-induced arrhythmias. The present study indirectly implicates stretch-activated ion channels in the genesis of stretch-related changes in repolarization and arrhythmias. The electrophysiologic changes after ventricular dilatation to a degree that increases left ventricular pressure in a clinically relevant range can be influenced by the stretch-activated channel blocker streptomycin but not by specific calcium channel block. This may have clinically important implications for the development of new antiarrhythmic drugs.

Animals↗