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Biomedical subjects

G Breithardt

Publications and source records attributed to G Breithardt.

At least 37 records · Page 2Linked to original sources
PubMed2003

QRS duration: a simple marker for predicting cardiac mortality in ICD patients with heart failure.

BACKGROUND: Patients resuscitated from ventricular tachyarrhythmias benefit from implantable cardioverter-defibrillators (ICDs) as opposed to medical treatment. Patients with increased QRS duration receiving an ICD in the presence of heart failure are at greatest risk of cardiac death and benefit most from ICD therapy. OBJECTIVE: To determine whether an increased QRS duration predicts cardiac mortality in ICD recipients. DESIGN: Consecutive patients with heart failure in New York Heart Association functional class III were grouped according to QRS duration (< 150 ms, n = 139, group 1; v > or = 150 ms, n = 26, group 2) and followed up for (mean (SD)) 23 (20) months. PATIENTS: 165 patients were studied (80% men, 20% women); 73% had coronary artery disease and 18% had dilated cardiomyopathy. Their mean age was 62 (10) years and mean ejection fraction (EF) was 33 (14)%. They presented either with ventricular tachycardia (VT) or ventricular fibrillation (VF). MAIN OUTCOME MEASURES: Overall and cardiac mortality; recurrence rates of VT, fast VT, or VF. RESULTS: Mean left ventricular EF did not differ between group 1 (33 (13)%) and group 2 (31 (15)%). Forty patients died (34 cardiac deaths). There was no difference in survival between patients with EF > 35% and < or = 35%. Cardiac mortality was significantly higher in group 2 than in group 1 (31.3% at 12 months and 46.6% at 24 months, v 9.5% at 12 months and 18.2% at 24 months, respectively; p = 0.04). The recurrence rate of VT was similar in both groups. CONCLUSIONS: Within subgroups at highest risk of cardiac death, QRS duration-a simple non-invasive index-predicts outcome in ICD recipients in the presence of heart failure.

Adolescent↗
PubMed2002

Relation of serum levels of sex hormone binding globulin to coronary heart disease in postmenopausal women.

Hyperandrogenemia and low levels of sex hormone binding globulin (SHBG) are frequently found in women with metabolic syndrome, which is characterized by low high-density lipoprotein cholesterol, hypertriglyceridemia, obesity, and hyperinsulinemia. The specific contribution of these various factors to coronary heart disease (CHD) is controversial. The coronary angiograms of 87 consecutive postmenopausal women were evaluated using 2 semiquantitative scoring systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, insulin, leptin, dehydroepiandrosterone sulfate, testosterone, and SHBG. Obesity was assessed by measuring body mass index, waist-to-hip ratio, skinfold thicknesses, and body impedance. After adjusting for age, there were significant differences in 55 women with CHD compared with 32 women without CHD: higher levels of low-density lipoprotein cholesterol (159 +/- 51 vs 132 +/- 39 mg/dl), apolipoprotein B (121 +/- 33 vs 102 +/- 29 mg/dl), triglycerides (115 vs 91 mg/dl), and basal insulin (7.5 vs 4.6 mU/L), as well as lower levels of high-density lipoprotein cholesterol (59.9 +/- 18.0 vs 69.0 +/- 17.1 mg/dl), SHBG (44.6 vs 68.1 nmol/L) and the quantitative insulin sensitivity check index (0.66 +/- 0.41 vs 0.93 +/- 0.73). Multivariate analysis by logistic regression identified age (odds ratio [OR] 1.22, 95% confidence intervals [CI] 1.09 to 1.37), smoking (OR 11.46, 95% CI 2.56 to 51.39), SHBG (OR 0.98, 95% CI 0.96 to 0.99), and apolipoprotein B (OR 1.02, 95% CI 1.01 to 1.04) as independently associated with the presence of CHD. Thus, low plasma levels of SHBG are associated with CHD in women independently of insulin, obesity markers, and dyslipidemia.

Androgens↗
PubMed2002

[Secondary prevention of coronary heart disease. Results from EuroASPIRE I and II in the region of Münster, Germany].

BACKGROUND: EuroASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) is a European multicenter study on secondary prevention in patients with coronary heart disease (CHD). The first cross-sectional survey was undertaken in 1995/96 among 3569 patients from nine countries. A second cross-sectional survey (EuroASPIRE II) was conducted in 1999/2000 among 5556 patients from 15 countries to evaluate among others whether coronary prevention had improved since the first. METHODS: The present study was conducted in the region of Münster, Germany, as part of the EuroASPIRE study. Consecutive patients, men and women up to 70 years of age with established CHD, were identified retrospectively. A total of 392 (EuroASPIRE I) and 402 (EuroASPIRE II) patients participated. Information on cardiovascular risk factors, lifestyle and medication were obtained through medical records, interviews and examinations. RESULTS: Both studies demonstrate a high prevalence of risk factors among CHD patients. At the time of the interview more than 60% of the patients in both surveys had two or more risk factors. The comparison of EuroASPIRE I and II reveals a substantial decrease of 20% in the prevalence of hypercholesterolemia, but an increase in the prevalence of hypertension and obesity. ACE-inhibitors, betablockers and lipid lowering drugs, especially statins, were used more frequently in EuroASPIRE II. CONCLUSIONS: We conclude that secondary prevention of CHD in the region of Münster like in the other European study regions is less than optimal and has not substantially improved between 1996 and 2000. Potential reasons are discussed.

Adult↗
PubMed2002

[Clinical aspects and molecular genetics of the Jervell- and Lange-Nielsen Syndrome].

In contrast to the Romano-Ward (R-W) syndrome, the Jervell and Lange-Nielsen (J-LN) syndrome is an autosomal recessive inherited disease characterized by QT-prolongation in the electrocardiogram (ECG) and recurrent syncopal attacks which are also typical for the R-W syndrome, but also by congenital deafness. Recently, defect alleles in the genes for KCNQ1 and KCNE1 have been identified in patients with the J-LN syndrome. These genes may be causative for the R-W syndrome as well but in J-LN patients, they are only present in the homozygote or compound heterozygote form. In the present paper, we review the clinical and genetic similarities and differences of the J-LN and the R-W syndrome as well as the diagnostic and therapeutic management of these patients and their family members.

DNA Mutational Analysis↗
PubMed2002

Associations of HDL phospholipids and paraoxonase activity with coronary heart disease in postmenopausal women.

A low high-density lipoprotein-cholesterol (HDL-C) is an established indicator for increased risk of coronary heart disease (CHD). Multiple functional relationships between HDL and CHD have been discussed. We tested the clinical relevance of some of these relationships in a cross-sectional coronary angiography (CA) study of 87 post-menopausal women between 48 and 73 years. In addition to established cardiovascular risk factors we measured concentrations of phosphatidylcholine (PC) and sphingomyelin (SPM) in HDL as indirect markers of cholesterol efflux capacity, the serum activity of the paraoxonase (PON) as a measure of the antioxidative capacity and serum concentrations of insulin/C-peptide and C-reactive protein (CRP) as indirect markers of insulin sensitivity and inflammation, respectively. Upon multivariate analysis of data from 55 women with angiographically assessed CHD differed from 32 women with angiographically excluded CHD, HDL-SPM had the strongest association with the presence of CHD among all HDL-related parameters. It was also the only HDL-related parameter which had a significant and independent correlation with the number of coronary stenoses. As HDL-SPM was previously shown to correlate with cholesterol efflux capacity of plasma, we conclude that reduced cholesterol efflux capacity is an important factor accounting for the inverse association between HDL-cholesterol and CHD.

Aged↗
PubMed2002

Electrophysiologic investigation in Brugada syndrome; yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats.

INTRODUCTION: Numerous reports on the inducibility of ventricular tachyarrhythmias (VT) in patients with atypical right bundle branch block and right precordial ST-elevation (Brugada syndrome) are based on multicentre studies that have used different stimulation protocols. Therefore, we prospectively investigated the inducibility of VT in these patients using a uniform protocol. METHODS: In 41 consecutive patients (29 males) showing a pattern of right bundle branch block and ST-elevation, programmed ventricular stimulation was performed in the right ventricular apex with up to three premature stimuli at sinus rhythm and at four different paced cycle lengths (500, 430, 370, and 330 ms) until refractoriness was reached or reproducible induction of a sustained (>30s) VT occurred. If a VT was not reproducibly inducible, the same protocol was repeated in the right ventricular outflow tract. RESULTS: A history of life-threatening events defined as syncope (n=17) or aborted sudden cardiac death (n=13) was present in 30 patients (73%); 11 individuals were asymptomatic. Inducibility (68%) was similar between symptomatic (n=21, 70%) and asymptomatic patients (n=7, 64%). In 16 (39%) patients, VT were reproducibly inducible. If patients were only stimulated in the right ventricular apex, inducibility rate decreased to 39%. If only two premature beats at two sites were used it was as low as 32%. The mean coupling intervals of the second and third premature stimuli inducing sustained VT were short: 189+/-21 ms vs 186+/-22 ms, respectively. Forty-four percent of all patients (i.e. 64% of the inducible patients) had inducible VT only with coupling intervals shorter than 200 ms. CONCLUSIONS: The stimulation protocol markedly influences the extent of inducibility of VT in patients with right bundle branch block and ST-segment elevation. These findings question the significance of previous multicentre studies using different stimulation protocols and should have implications for further studies.

Adult↗
PubMed2002

Programmed ventricular stimulation: influence of early versus late introduction of a third extrastimulus, a randomized, prospective study.

OBJECTIVE: The aim of this prospective study was to analyze the yield of early vs late introduction of a third extra-stimulus during programmed ventricular stimulation. METHODS: Two randomized protocols of programmed ventricular stimulation were used in 94 consecutive patients with coronary artery disease who were studied because of non-sustained ventricular tachycardia (9.6%), sustained monomorphic ventricular tachycardia (46.8%), ventricular fibrillation (18.1) or syncope (25.5%). During protocol A, a third extrastimulus was introduced during a basic drive cycle length of 500 ms after completion of programmed ventricular stimulation with 1 and 2 extrastimuli during sinus rhythm and paced cycle lengths of 500, 430. 370 and 330 ms. During protocol B, the third extrastimulus was introduced early (after 1 and 2 extrastimuli during sinus rhythm and a paced cycle length of 500 ms). Both protocols began at the right ventricular apex. If sustained ventricular tachyarrhythmia had been induced, the same sequence of programmed ventricular stimulation was repeated at the right ventricular outflow tract. RESULTS: The overall incidence of induced arrhythmias did not differ between the two protocols. However, the use of the third extrastimulus (both protocols) increased the yield of ventricular fibrillation induction significantly (P < 0.04) compared with ventricular tachycardia induction. CONCLUSIONS: The introduction of the third extrastimulus should be considered only at the end of stimulation protocols (especially in those patients without previously documented sustained ventricular tachyarrhythmias) in order to prevent induction of polymorphic ventricular tachycardia or fibrillation.

Adult↗
PubMed2002

Task Force on Sudden Cardiac Death, European Society of Cardiology.

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.

Advisory Committees↗
PubMed2001

Molecular diagnosis in a child with sudden infant death syndrome.

Although sudden infant death syndrome (SIDS) has been associated with long QT syndrome-a genetic disorder that causes arrhythmia-a causal link has not been shown. We screened genomic DNA from a child who died of SIDS and identified a de-novo mutation in KVLQT1, the gene most frequently associated with long QT syndrome. This mutation (C350T) had already been identified in an unrelated family that was affected by long QT syndrome. These results confirm the hypothesis that some deaths from SIDS are caused by long QT syndrome and support implementation of neonatal electrocardiographic screening.

Adolescent↗
PubMed2001

De novo mutation in the SCN5A gene associated with early onset of sudden infant death.

BACKGROUND: Congenital long QT syndrome (LQTS), a cardiac ion channel disease, is an important cause of sudden cardiac death. Prolongation of the QT interval has recently been associated with sudden infant death syndrome, which is the leading cause of death among infants between 1 week and 1 year of age. Available data suggest that early onset of congenital LQTS may contribute to premature sudden cardiac death in otherwise healthy infants. METHODS AND RESULTS: In an infant who died suddenly at the age of 9 weeks, we performed mutation screening in all known LQTS genes. In the surface ECG soon after birth, a prolonged QTc interval (600 ms(1/2)) and polymorphic ventricular tachyarrhythmias were documented. Mutational analysis identified a missense mutation (Ala1330Pro) in the cardiac sodium channel gene SCN5A, which was absent in both parents. Subsequent genetic testing confirmed paternity, thus suggesting a de novo origin. Voltage-clamp recordings of recombinant A1330P mutant channel expressed in HEK-293 cells showed a positive shift in voltage dependence of inactivation, a slowing of the time course of inactivation, and a faster recovery from inactivation. CONCLUSIONS: In this study, we report a de novo mutation in the sodium channel gene SCN5A, which is associated with sudden infant death. The altered functional characteristics of the mutant channel was different from previously reported LQTS3 mutants and caused a delay in final repolarization. Even in families without a history of LQTS, de novo mutations in cardiac ion channel genes may lead to sudden cardiac death in very young infants.

Age of Onset↗
PubMed2001

xIAP induces cell-cycle arrest and activates nuclear factor-kappaB : new survival pathways disabled by caspase-mediated cleavage during apoptosis of human endothelial cells.

Survival of human vascular endothelial cells depends on their ability to activate the transcription factor nuclear factor-kappaB (NF-kappaB), a regulator of antiapoptotic genes, such as the X chromosome-linked inhibitor of apoptosis protein (xIAP). In the present study, we demonstrated expression of xIAP in the endothelial lining of normal human arteries and veins and elevated levels in highly malignant human endothelial tumors. Using retroviral infection of human endothelial cells, we identified two novel survival mechanisms mediated by xIAP in endothelial cells. First, xIAP can activate the transcription factor NF-kappaB, a known survival factor for human endothelial cells. This positive feedback loop induced by xIAP is mediated via phosphorylation and sustained degradation of inhibitor (I) kappaBalpha. Second, xIAP can inhibit cell proliferation via downregulation of cyclins A and D1 and induction of the cyclin-dependent kinase inhibitors p21(Cip1/Waf1) and p27(Kip1). Cleavage of xIAP by caspases during endothelial cell apoptosis disables both of these biological functions of xIAP. Thus, caspase-mediated cleavage of xIAP interrupts a positive regulatory cytoprotective loop between NF-kappaB and xIAP and increases the vulnerability of the cell to apoptosis by releasing it from an xIAP-mediated quiescent state.

Apoptosis↗
PubMed2001

Genotype-phenotype correlation in the long-QT syndrome: gene-specific triggers for life-threatening arrhythmias.

BACKGROUND: The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific. METHODS AND RESULTS: We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with ss-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients. CONCLUSIONS: Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches.

Adrenergic beta-Antagonists↗