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Biomedical subjects

Günter Breithardt

Publications and source records attributed to Günter Breithardt.

At least 19 recordsLinked to original sources
PubMed2003

Dynamic regulation of MEK/Erks and Akt/GSK-3beta in human end-stage heart failure after left ventricular mechanical support: myocardial mechanotransduction-sensitivity as a possible molecular mechanism.

OBJECTIVE: Left ventricular assist devices (LVAD) are used to 'bridge' patients with end-stage heart failure to transplantation. After long-term LVAD support, ventricular function may partially recover, a process called 'reverse remodeling'. As several kinase-mediated signal transduction pathways have been implicated in the development of cardiac hypertrophy and failure, we examined the activities of the Erks, MEKs, Akt, GSK-3 beta, p70S6K, JNKs and p38 under LVAD support as well as during single myocyte strain and whole heart stretch. METHODS: Western blotting and immunohistochemistry were performed using phospho-specific antibodies in matched samples from ten patients with end-stage heart failure before and after LVAD. Cyclic strain was performed in rat neonatal cardiac myocytes, and tensile stretch applied to Langendorff-perfused mouse hearts via a left ventricular balloon. RESULTS: The activity of Erks and Akt in failing hearts dramatically decreased after LVAD support, while that of GSK-3 beta increased. There was an endo/epicardial gradient for Erk activity which persisted after LVAD despite the reduction of total Erk activity. TUNEL-positivity and myocyte size decreased after LVAD, but independently of changes in kinase activity. In cardiomyocytes and Langendorff-perfused mouse hearts both strain/stretch and its relief regulated the activities of Erks, Akt, and GSK-3 beta. CONCLUSION: Erks and Akt/GSK-3 beta are highly responsive to myocyte stretch in vitro and in vivo, and may be sensitive molecular parameters of 'reverse remodeling' under LVAD support.

Adolescent↗
PubMed2003

Reentrant circuits in the canine atrioventricular node during atrial and ventricular echoes: electrophysiological and histological correlation.

BACKGROUND: The anatomic-electrophysiological correlation of AV nodal reentry is unclear. To localize reentrant circuits during atrial and ventricular echoes and to characterize sites of slow conduction and block, we correlated histology with electrophysiology of the AV node. METHODS AND RESULTS: In 10 isolated dog hearts, extracellular electrical activity was recorded in Koch's triangle at 208 or 247 sites (interelectrode distance, 0.5 and 0.3 mm) after removal of 0.7 to 1.5 mm of overlying atrial tissue. Resection did not affect refractory periods. Five hearts were subjected to histology. Complete atrial echoes were induced in 1 heart, incomplete atrial echoes in 5 hearts. Unidirectional conduction block occurred at the atrial-transitional cell junction in the superior area. Zones of slow conduction arose at the atrial-transitional or the transitional-compact node junction in the inferior area. Complete reentrant circuits of ventricular echoes were obtained in 5 hearts. Unidirectional conduction block occurred at the compact node-transitional cell junction in the superior area. Localized zones of slow conduction arose at the junctions between the different types of tissue in the inferior area. CONCLUSIONS: In the dog heart, tissue architecture and functional dissociation between the inferior and the superior region of the AV node enable dual physiology and reentry. Slow conduction and functional conduction block occur at the junctions between the different types of tissue in the AV nodal area. Atrial echoes were enabled by conduction block at the atrial-transitional cell junction, whereas during ventricular echoes conduction block occurred at the compact node-transitional cell junction.

Animals↗
PubMed2003

Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in DeltaKPQ SCN5A (long QT3) mice.

OBJECTIVE: It has been suggested that both pacing and treatment with mexiletine may reduce torsade de pointes (TdP) arrhythmias in patients with long QT syndrome 3 (LQT3), but it is not fully understood how these interventions could prevent TdP. We therefore studied the effects of pacing and mexiletine in mice with a heterozygous knock-in DeltaKPQ SCN5A(Delta/+) deletion (SCN5A-Tg), a murine LQT3 model. METHODS: Three right and left ventricular monophasic action potentials (MAPs) were simultaneously recorded in Langendorff-perfused hearts of SCN5A-Tg and wild type (WT) littermates. AV block was induced, and pacing was performed at baseline and during mexiletine infusion (4 microg/ml). MAP recordings were analysed for action potential duration (APD), APD dispersion, and early afterdepolarisations (EADs) and related to spontaneous arrhythmias. RESULTS: After inducing AV block, SCN5A-Tg hearts were bradycardic [SCN5A-Tg 532+/-60 vs. WT 284+/-48 ms cycle length (CL, mean+/-S.E.M., P<0.05(*))]. EADs occurred in 16/18, and polymorphic ventricular tachycardia (pVT) in 11/18 SCN5A-Tg but not in 19 WT. SCN5A-Tg had longer APD than WT hearts*. At CL of 200 ms and longer, APD dispersion was higher in SCN5A-Tg [dispersion (APD70): 12+/-3 ms vs. 5+/-2 ms at CL=200 ms*], and increased to 35+/-4 ms* directly prior to pVT episodes. Sudden rate accelerations initially increased APD dispersion due to EADs and APD alternans in SCN5A-Tg, but pacing then reduced APD dispersion. Pacing suppressed (n=9/9) and prevented (n=49/50) pVT. Mexiletine shortened APD at long CL*, and suppressed pVT (n=4/5*), but did not prevent pVT during normal rhythm. CONCLUSIONS: Bradycardia, increased dispersion of APD and EADs provoke ventricular ectopy and pVT in SCN5A-Tg hearts. Ventricular pacing reduces APD dispersion, suppresses EADs and prevents pVT in SCN5A-Tg hearts. These effects provide a pathophysiological rationale for pacing in LQT3.

Action Potentials↗
PubMed2003

Prolonged action potential durations, increased dispersion of repolarization, and polymorphic ventricular tachycardia in a mouse model of proarrhythmia.

INTRODUCTION: In the congenital long QT syndrome, inhomogeneously prolonged action potentials, bradycardia, and hypokalemia can cause afterdepolarizations and torsade de pointes. Other genetic factors may contribute to similar forms of ventricular tachycardias in hypertrophied or failing hearts, especially if the outward current I(Kr) is blocked pharmacologically. We sought to develop a mouse heart model for such arrhythmias in order to identify the proarrhythmic potential in transgenic animals. METHODS AND RESULTS: Hearts of adult wild-type (CD1) mice were isolated and the aorta was retrogradely perfused. Three monophasic action potentials and a volume-conducted ECG were simultaneously recorded. Sotalol (10(-5)M and 2 x 10(-5)M) prolonged action potential duration (APD) in a concentration-dependent and reverse frequency-dependent fashion (from 34 +/- 1 to 48 +/- 2 ms at 100 ms basic cycle length (BCL), from 38 +/- 2 to 54 +/- 3 ms at 180 ms BCL for APD90, p < 0.05). Sotalol did not alter the relation between refractoriness and APD (ERP/APD ratio = 0.76 - 0.93). AV nodal block caused ventricular bradycardia and doubled dispersion of APD (APD70max-min: 11 +/- 1 vs. 4 +/- 1 ms, APD90max-min: 12 +/- 1 vs. 5 +/- 1 ms, p < 0.05). If combined with hypokalemia, afterdepolarizations induced polymorphic ventricular tachycardias in 1 of 8 hearts at K(+) =3.0 mM and in 10 of 12 hearts at K(+) = 2.0 mM. Prior to polymorphic ventricular tachycardia, dispersion of APD further increased (APD70max-min: 17 +/- 3 ms; APD90max-min: 25 +/- 3 ms; p < 0.05). CONCLUSIONS: This isolated beating mouse heart model can be used to study drug-induced action potential prolongation and repolarization-related ventricular arrhythmias provoked by bradycardia and hypokalemia. It may be suitable to identify a genetic predisposition to ventricular arrhythmias that may only become apparent under such proarrhythmic conditions.

Action Potentials↗
PubMed2003

The ajmaline challenge in Brugada syndrome: diagnostic impact, safety, and recommended protocol.

AIMS: The diagnostic ECG pattern in Brugada syndrome (BS) can transiently normalize and may be unmasked by sodium channel blockers such as ajmaline. Proarrhythmic effects of the drug have been well documented in the literature. A detailed protocol for the ajmaline challenge in Brugada syndrome has not yet been described. Therefore, we prospectively studied the risks of a standardized ajmaline test. METHODS AND RESULTS: During a period of 60 months, 158 patients underwent the ajmaline test in our institution. Ajmaline was given intravenously in fractions (10mg every two minutes) up to a target dose of 1mg/kg. In 37 patients (23%) the typical coved-type ECG pattern of BS was unmasked. During the test, symptomatic VT appeared in 2 patients (1.3%). In all other patients, the drug challenge did not induce VT if the target dose, QRS prolongation >30%, presence/appearance of the typical ECG, or the occurrence of premature ventricular ectopy were considered as end points of the test. A positive response to ajmaline was induced in 2 of 94 patients (2%) with a normal baseline ECG, who underwent evaluation solely for syncope of unknown origin. CONCLUSION: The ajmaline challenge using a protocol with fractionated drug administration is a safe method to diagnose BS. Because of the potential induction of VT, it should be performed under continuous medical surveillance with advanced life-support facilities. Due to the prognostic importance all patients with aborted sudden death or unexplained syncope without demonstrable structural heart disease and family members of affected individuals should presently undergo drug testing for unmasking BS.

Adolescent↗
PubMed2003

In vivo recording of monophasic action potentials in awake dogs.

Assessment of cardiac repolarization in dogs in vivo is of interest in numerous experimental canine models. Previous studies have used monophasic action potentials (MAPs) to investigate repolarization in vitro and in vivo in anesthetized animal models. Therefore, an approach for recording MAPs in awake dogs without the interference of anesthesia is desirable. We describe an experimental technique to record MAPs in conscious dogs by means of conventional rubber introducers which are implanted into the internal jugular vein. Atrial as well as ventricular MAPs can be simultaneously measured without complications. Pacing thresholds are low and stable over time. Continuous MAP recordings of stable amplitude can be achieved from the same endocardial site for periods up to 1h. Antegrade and retrograde atrioventricular nodal conduction properties can be assessed. Programmed stimulation can be performed to simultaneously determine local refractory periods and MAP duration at cycle lengths from 500 to 200ms. In awake, unsedated dogs measuring MAPs via rubber introducers permits safe, long-term recording of MAPs. Such recordings may be useful for safety pharmacologic studies in evaluating cardiovascular and noncardiovascular drugs with respect to their effects on repolarization. In various canine in vivo models including in vivo models of long QT syndrome, heart failures or sudden cardiac death, the present technique permits electrophysiologic measurements without the interference of anesthesia.

Action Potentials↗
PubMed2003

ICD leads: design and chronic dysfunctions.

The treatment of ventricular tachyarrhythmias has changed over the last 10 years. Implantable cardioverter defibrillators (ICDs), once used only as a last resort therapy, have now become the treatment of choice. This change occurred before the first results of randomized studies on ICD therapy in patients with life-threatening ventricular tachyarrhythmias were published by the end of 1997. Technological advances of ICD therapy, in particular the development of transvenous leads, were to a large extent responsible for this change. Modern leads are characterized by their multilumen design that incorporates straight wires and coiled conductors into a single electrode body. Conductors and insulation are sheathed with additional insulation layers. The most frequently used insulating materials are silicone, polyurethane, and fluoropolymers. Lead failures are an important complication of ICD therapy. Fractured conductors, compression, creeping, or insulation defects from abrasion can cause such lead dysfunctions. Chronically implanted leads will inevitably have an increased risk of failure due to defects despite all technological advances. In the light of improving survival figures in patients with ventricular tachyarrhythmias and increasing numbers of ICD implantations, lead failures are becoming a clinical problem of ever increasing importance. Therefore, the question of which lead types necessitate extraction when a certain failure occurs and which leads can be left in place. Despite continuous improvements in lead extraction systems and growing experience in their use, the extraction of any pacemaker or ICD lead is associated with some risk of complications.

Defibrillators, Implantable↗
PubMed2003

Mortality, morbidity, and complications in 3344 patients with implantable cardioverter defibrillators: results fron the German ICD Registry EURID.

ICDs are the therapy of choice in patients with life-threatening ventricular arrhythmias. Mortality, morbidity, and complication rates including appropriate and inappropriate therapies are unknown when ICDs are used in routine medical care and not in well-defined patients included in multicenter trials. Therefore, the data of 3,344 patients (61.1 +/- 12.1 years; 80.2% men; CAD 64.6%, dilated cardiomyopathy 18.9%; NYHA Class I-III: 19.1%, 54.3%, 20.1%, respectively; LVEF > 0.50: 0.234, LVEF 0.30-0.50: 0.472, LVEF < 0.30: 0.293, respectively) implanted in 62 German hospitals between January 1998 and October 2000 were prospectively collected and analyzed as a part of the European Registry of Implantable Defibrillators (EURID Germany). The 1-year survival rate was 93.5%. Patients in NYHA Class III and aLVEF < 0.30 had a lower survival rate than patients in NYHA Class I and a preserved LVEF (0.852 vs 0.975,P = 0.0001). Including the 1-year follow-up, 49.5% of patients had an intervention by the ICD, 39.8% had appropriate ICD therapies, 16.2% had inappropriate therapies. Overall, 1,691 hospital readmissions were recorded. The main causes for hospital readmissions were ventricular arrhythmias (61.3%) and congestive heart failure symptoms (12.9%). Thus, demographic data and mortality of patients treated with an ICD in conditions of standard medical care seems to be comparable and based on, or congruent with, the large secondary preventions trials. When ICDs are used in standard medical care, the 1-year survival rate is high, especially in patients with NYHA Class I and preserved LVEF. However, nearly half of all patients suffer from ICD intervention.

Defibrillators, Implantable↗
PubMed2003

Grade of chronic renal failure, and acute and long-term outcome after percutaneous coronary interventions.

BACKGROUND: Patients with moderate chronic renal failure have recently been identified to suffer from a markedly higher mortality after percutaneous coronary intervention (PCI). We focused on the outcome of PCI patients with just mildly elevated creatinine levels of 1.1 to 1.5 mg/dL. METHODS: Data of all PCI patients of the years 1998 to 1999 were analyzed. Follow-up was performed by a questionnaire sent to all patients. RESULTS: During this period, PCI was performed in 1049 patients. Long-term follow-up (1184 +/- 10 days) was 99.6% complete. Total mortality increased continuously by each creatinine increment of 0.1 mg/dL above 1.0 mg/dL, with a significant difference at 1.3 mg/dL compared to patients with <or=1.0 mg/dL (12.4 vs. 5.5%, P < 0.05). In a Kaplan-Meier model, patients with a creatinine of 1.3 to 1.4 mg/dL had a significantly lower cumulative survival after three years (87%) than controls (96%, P = 0.0108, log rank test). Higher serum creatinine levels were found to be significantly associated with death in univariate analysis (1.1 +/- 0.4 vs. 1.5 +/- 1.0 mg/dL, P < 0.00001), and in multivariate analysis by stepwise logistic regression (OR 2.122, 95% CI 1.585 to 2.841). CONCLUSIONS: In this retrospective cross-sectional study, even patients with slightly elevated serum creatinine levels of 1.3 to 1.4 mg/dL had a significantly reduced long-term outcome after PCI. Thus, even mild chronic renal failure appears to be associated with markedly increased risk after a PCI, with implications to the high number of patients concerned.

Aged↗
PubMed2003

Endocardial mapping of right ventricular outflow tract tachycardia using noncontact activation mapping.

INTRODUCTION: Activation mapping and pace mapping identify successful ablation sites for catheter ablation of right ventricular outflow tract (RVOT) tachycardia. These methods are limited in patients with nonsustained tachycardia or isolated ventricular ectopic beats. We investigated the feasibility of using noncontact mapping to guide the ablation of RVOT arrhythmias. METHODS AND RESULTS: Nine patients with RVOT tachycardia and three patients with ectopic beats were studied using noncontact mapping. A multielectrode array catheter was introduced into the RVOT and tachycardia was analyzed using a virtual geometry. The earliest endocardial activation estimated by virtual electrograms was displayed on an isopotential color map and measured 33 +/- 13 msec before onset of QRS. Virtual unipolar electrograms at this site demonstrated QS morphology. Guided by a locator signal, ablation was performed with a mean of 6.9 +/- 2.2 radiofrequency deliveries. Acute success was achieved in all patients. During follow-up, one patient had a recurrence of RVOT tachycardia. Compared with patients (n = 21) who underwent catheter ablation using a conventional approach, a higher success rate was achieved by noncontact mapping. Procedure time was significantly longer in the noncontact mapping group. Fluoroscopy time was not significantly different in the two groups. CONCLUSION: Noncontact mapping can be used as a reliable tool to identify the site of earliest endocardial activation and to guide the ablation procedure in patients with RVOT tachycardia and in patients with ectopic beats originating from the RVOT.

Adult↗
PubMed2003

Effect of sotalol and acute ventricular dilatation on action potential duration and dispersion of repolarization after defibrillation shocks.

Ventricular dilatation shortens action potential duration and increases the defibrillation threshold, whereas sotalol prolongs action potential duration and may decrease the defibrillation threshold. Whether these action potential changes remain after defibrillation shocks, and how they relate to defibrillation success, is not known. In this study, eight monophasic action potentials were recorded simultaneously during electrical defibrillation (shock strength: 20%-200% of the defibrillation threshold) in 16 normal and acutely dilated isolated rabbit hearts at baseline and after addition of sotalol (2 x 10-5 M). Post-shock action potential duration (PS-APD) and dispersion of PS-APD [Disp(PS-APD)] of monophasic action potentials were analyzed after 322 defibrillation shocks at different repolarization levels and related to defibrillation success. Acute ventricular dilatation shortened PS-APD, whereas sotalol prolonged PS-APD. Successful defibrillation was associated with lower Disp(PS-APD) at all repolarization levels in the normal and dilated heart at baseline and with sotalol (mean difference: 33%-46%, all P < 0.005). Minimal PS-APD was longer (mean difference: 5%-11%), while maximal PS-APD was shorter (mean difference: 2%-16%) after successful defibrillation shocks than after failing defibrillation shocks. Therefore, sotalol prolongs action potential duration after defibrillation shocks. Synchronization of repolarization, caused by both prolongation of short PS-APD and shortening of long PS-APD, is associated with successful defibrillation in the normal, acutely dilated, and sotalol-treated heart.

Action Potentials↗
PubMed2003

Amiodarone-induced postrepolarization refractoriness suppresses induction of ventricular fibrillation.

It is still incompletely understood why amiodarone is such a potent antiarrhythmic drug. We hypothesized that chronic amiodarone treatment produces postrepolarization refractoriness (PRR) without conduction slowing and that PRR modifies the induction of ventricular arrhythmias. In this study, the hearts of 15 amiodarone-pretreated (50 mg/kg p.o. for 6 weeks) rabbits and 13 controls were isolated and eight monophasic action potentials were simultaneously recorded from the epicardium and endocardium of both ventricles. Steady-state action potential duration (APD), conduction times, refractory periods, and dispersion of action potential durations were determined during programmed stimulation and during 50-Hz burst stimuli, and related to arrhythmia inducibility. Amiodarone prolonged APD by 12 to 15 ms at pacing cycle lengths of 300 to 600 ms (p < 0.05) but did not significantly increase conduction times or dispersion of APD. Amiodarone prolonged refractoriness more than action potential duration, resulting in PRR (refractory period - APD at 90% repolarization, 14 +/- 10 ms, p < 0.05 versus controls). PRR curtailed the initial sloped part of the APD restitution curve by 20%. During burst stimulation, pronounced amiodarone-induced PRR (40 +/- 15 ms, p < 0.05 versus controls) reduced the inducibility of ventricular arrhythmias (p < 0.05 versus controls). Furthermore, in 35% of bursts only monomorphic ventricular tachycardias and no longer ventricular fibrillation were inducible in amiodarone-treated hearts (p < 0.05 versus controls). Chronic amiodarone treatment prevents ventricular tachycardias by inducing PRR without much conduction slowing, thereby curtailing the initial part of APD restitution. PRR without conduction slowing is a desirable feature of drugs designed to prevent ventricular arrhythmias.

Action Potentials↗
PubMed2003

Molecular site of action of the antiarrhythmic drug propafenone at the voltage-operated potassium channel Kv2.1.

The effects of the antiarrhythmic drug propafenone at Kv2.1 channels were studied with wild-type and mutated channels expressed in Xenopus laevis oocytes. Propafenone decreased the Kv2.1 currents in a time- and voltage-dependent manner (decrease of the time constants of current rise, increase of block with the duration of voltage steps starting from a block of less than 19%, increase of block with the amplitude of depolarization yielding a fractional electrical distance delta of 0.11 to 0.16). Block of Kv2.1 appeared with application to the intracellular, but not the extracellular, side of membrane patches. In mutagenesis experiments, all parts of the Kv2.1 channel were successively exchanged with those of the Kv1.2 channel, which is much more sensitive to propafenone. The intracellular amino and carboxyl terminus and the intracellular linker S4-S5 reduced the blocking effect of propafenone, whereas the linker S5-S6, as well as the segment S6 of the Kv1.2 channel, abolished it to the value of the Kv1.2 channel. In the linker S5-S6, this effect could be narrowed down to two groups of amino acids (groups 372 to 374 and 383 to 384), which also affected the sensitivity to tetraethylammonium. In segment S6, several amino acids in the intracellularly directed part of the helix significantly reduced propafenone sensitivity. The results suggest that propafenone blocks the Kv2.1 channel in the open state from the intracellular side by entering the inner vestibule of the channel. These results are consistent with a direct interaction of propafenone with the lower part of the pore helix and/or residues of segment S6.

Amino Acid Sequence↗
PubMed2003

Vascular ligation response is independent of p107: stressing the role of the related p130.

Recent studies have revealed the role of the pRb family members pRb and p130 in the response to vascular injury. We evaluated the arterial injury response in the absence of p107, a protein that shares a high degree of homology with the injury-controlling p130. Carotid artery ligation and perivascular electric injury of the femoral artery were applied to p107 knockout (p107 -/-) mice, and morphometric analysis was performed 3 wk after ligation and electric injury. Arterial vessels of p107 -/- mice were indistinguishable from controls under basal conditions. After carotid artery ligation the p107 -/- mice (n = 7) did not display an enhanced ligation response compared with controls (n = 9), which was studied over a distance of approximately 450 microm proximal and approximately 200 microm distal from the ligation site, with regard to vessel wall area, neointima area, and lumen area. Corresponding with this, morphometric data obtained from the perivascular electric injury of the femoral artery confirmed the lack of enhanced ligation and injury response in the absence of p107. We conclude that the pRb family member p107 is not a key regulator in vascular injury response. These data, in conjunction with previously reported results, indicate that the control of vascular injury response is not a redundant feature of pRb proteins but primarily specific for p130. Further studies on functional domains of p130 and p107 will help to resolve the pathways in vascular injury response.

Animals↗
PubMed2003

Pacemaker channel dysfunction in a patient with sinus node disease.

The cardiac pacemaker current I(f) is a major determinant of diastolic depolarization in sinus nodal cells and has a key role in heartbeat generation. Therefore, we hypothesized that some forms of "idiopathic" sinus node dysfunction (SND) are related to inherited dysfunctions of cardiac pacemaker ion channels. In a candidate gene approach, a heterozygous 1-bp deletion (1631delC) in exon 5 of the human HCN4 gene was detected in a patient with idiopathic SND. The mutant HCN4 protein (HCN4-573X) had a truncated C-terminus and lacked the cyclic nucleotide-binding domain. COS-7 cells transiently transfected with HCN4-573X cDNA indicated normal intracellular trafficking and membrane integration of HCN4-573X subunits. Patch-clamp experiments showed that HCN4-573X channels mediated I(f)-like currents that were insensitive to increased cellular cAMP levels. Coexpression experiments showed a dominant-negative effect of HCN4-573X subunits on wild-type subunits. These data indicate that the cardiac I(f) channels are functionally expressed but with altered biophysical properties. Taken together, the clinical, genetic, and in vitro data provide a likely explanation for the patient's sinus bradycardia and the chronotropic incompetence.

Aged↗
PubMed2003

The long QT syndrome: considerations in the athletic population.

In athletes, ventricular arrhythmias and sudden cardiac death are rare and unpredictable events. Often, an underlying heart disease is present, but pre-existing clinical signs or symptoms may not be recognized. Primary electrical disorders (such as the long QT syndrome) are rarely present in athletes but, so far, are a considerable reason for disqualification from sport activity. These disorders are mostly inherited, and patients should be referred to a cardiologist with special experience. Through the efforts of molecular genetics and cellular electrophysiology, an increasing understanding of the underlying mechanisms of arrhythmogenesis is being gathered. During the past decade, evidence has grown that establishing accurate genetic diagnoses and dissection of molecular disease mechanisms can have an impact on prognosis, and help direct therapy in a range of cardiovascular diseases. Further achievements in the areas of clinical and molecular research, improvement of medical education, and expansion of genotyping facilities will facilitate the correct and immediate identification of affected patients.

Adolescent↗
PubMed2002

Anterior-posterior versus anterior-lateral electrode positions for external cardioversion of atrial fibrillation: a randomised trial.

BACKGROUND: External cardioversion is a readily available treatment for persistent atrial fibrillation. Although anatomical and electrophysiological considerations suggest that an anterior-posterior electrode position should create a more homogeneous shock-field gradient throughout the atria than an anterior-lateral position, both electrode positions are equally recommended for external cardioversion in current guidelines. We undertook a randomised trial comparing the two positions with the endpoint of successful cardioversion. METHODS: 108 consecutive patients (mean age 60 years [SD 16]) with persistent atrial fibrillation (median duration 5 months, range 0.1-120) underwent elective external cardioversion by a standardised step-up protocol with increasing shock strengths (50-360 J). Electrode positions were randomly assigned as anterior-lateral or anterior-posterior. If sinus rhythm was not achieved with 360 J energy, a single cross-over shock (360 J) was applied with the other electrode configuration. A planned interim analysis was done after these patients had been recruited; it was by intention to treat. FINDINGS: Cardioversion was successful in a higher proportion of the anterior-posterior than the anterior-lateral group (50 of 52 [96%] vs 44 of 56 [78%], difference 23.7% (95% CI 9.1-37.8, p=0.009). Cross-over from the anterior-lateral to the anterior-posterior electrode position was successful in eight of 12 patients, whereas cross-over in the other direction was not successful (two patients). After cross-over, cardioversion was successful in 102 of 108 randomised patients (94%). INTERPRETATION: An anterior-posterior electrode position is more effective than the anterior-lateral position for external cardioversion of persistent atrial fibrillation. These results should be considered in clinical practice, for the design of defibrillation electrode pads, and when guidelines for cardioversion of atrial fibrillation are updated.

Adolescent↗