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Biomedical subjects

M Borggrefe

Publications and source records attributed to M Borggrefe.

At least 127 records · Page 7Linked to original sources
PubMed1996

Predictive value of wavelet correlation functions of signal-averaged electrocardiogram in patients after anterior versus inferior myocardial infarction.

OBJECTIVES: This study sought to evaluate the prognostic value of wavelet correlation functions of the signal-averaged electrocardiogram (ECG) for arrhythmic events in patients after myocardial infarction. BACKGROUND: Wavelet transform of the signal-averaged ECG has been shown to be a nonstationary analysis technique describing the time evolution of frequency spectra throughout the QRS complex. To quantify the wavelet transform, we introduced the new concept of the wavelet correlation function. METHODS: The relation among wavelet correlation functions, ventricular late potentials and the site of infarction was investigated in 769 men < 66 years old who survived the acute phase of myocardial infarction (351 [46%] anterior, 418 [54%] inferior infarctions). Signal-averaged ECG recordings were obtained 2 to 3 weeks after infarction. During 6 months of follow-up, 33 patients (4.3%) experienced a malignant arrhythmic event. Wavelet correlation functions of the signal-averaged ECG were evaluated in a time-frequency plane ranging from 25 ms before QRS onset to 25 ms after QRS offset in the frequency range between 40 and 100 Hz. RESULTS: Patients with an anterior infarction had lower mean wavelet correlation coefficients (p < 0.001) and a lower incidence of ventricular late potentials than patients with an inferior infarction (32.3% vs. 42.7%, p = 0.003). The combination of wavelet correlation functions and late potentials increased the total predictive accuracy from 52% to 72% for inferior and from 64% to 76% for anterior infarctions. CONCLUSIONS: Spectral changes in the signal-averaged QRS complex are more prominent in anterior than inferior infarctions. Combination of late potential analysis and wavelet correlation functions increases the prognostic value for serious arrhythmic events after myocardial infarction.

Adult↗
PubMed1996

Multiresolution decomposition of the signal-averaged ECG using the mallat approach for prediction of arrhythmic events after myocardial infarction.

The aim of this study was to analyze the ability of the multiresolution decomposition of the signal-averaged electrocardiogram (ECG) to discriminate between patients who develop life-threatening ventricular arrhythmias after myocardial infarction and those who do not and to compare the predictive values of this approach with those obtained from the analysis of ventricular late potentials in the time domain. Signal-averaged ECGs of 769 prospectively included patients were analyzed. A total of 42 arrhythmic events occurred during the follow-up period. For numerical calculations of wavelet analysis, the total and relative energies of the QRS complex were obtained in seven frequency bands. The combination of the relative energy in the frequency bands 7.8-15.6 Hz and 62.5-125 Hz enhanced statistical performance as compared with the time-domain parameters (positive predictive accuracy, 11.3 vs 8.2%). Combining wavelet transform and time-domain parameters enhanced the predictive values even more (positive predictive accuracy, 14.3%) compared with applying each method alone.

Adult↗
PubMed1996

Heart rate variability in time domain after acute myocardial infarction.

These results suggest that analysis of heart rate variability recorded even very early after acute myocardial infarction (1 to 2 days after onset of pain) is feasible in clinical routine and strongly related to subsequent arrhythmic events and cardiac mortality. Decreased HRV is considered not only a marker of impaired vagal activity of the heart but complete autonomic impairment, strongly associated with the degree of myocardial damage. HRV represents the integrated response of the cardiovascular system to a variety of different influences: the plasma level of catecholamines, the baroreflex activation and the direct sympathetic and vagal activity. The HRV profile is dynamic-HRV reduction caused by myocardial damage changes over time presenting a progressive increase up to normality over a 2-month follow-up. The observed early differences between anterior and inferior myocardial infarction disappear later in the healing phase. However, group analysis results of different HRV indices are stabile over time and highly reproducible, but presenting large individual variations. HRV parameters which are adjusted to heart rate (e. g. CV) seemed to be more stabile. The role of HRV analysis in risk stratification of patients after myocardial infarction is strongly related to the actual model of the genesis of ventricular arrhythmias. Multiple experimental and clinical studies described the development of life threatening ventricular arrhythmias as a multifactorial event which can not be described adequately using just one risk parameter for stratification. The arrhythmogenic substrate representing the underlying inhomogeneity of electrical behaviour of adjacent myocardial areas might be detectable by the analysis of ventricular late potentials or frequency disturbances from the signal averaged ECG. The autonomic modulation of this substrate is represented by an altered heart rate variability. Possible trigger factors to initiate arrhythmias in a modulated arrhythmogenic substrate like ventricular premature beats or transient myocardial ischemia can be detected by conventional arrhythmia and ST segment analysis from Holter tapes. The optimized combination of these non-invasive risk predictors together with well known evident clinical risk parameters, like left ventricular ejection fraction, may lead to a valid set of screening parameters for individual risk estimation after myocardial infarction.

Autonomic Nervous System↗
PubMed1996

Temperature-controlled radiofrequency catheter ablation of manifest accessory pathways.

OBJECTIVES: The primary objectives of this study were to assess the feasibility of temperature-controlled radiofrequency catheter ablation of left and right sided manifest accessory pathways in patients with Wolff-Parkinson-White syndrome and to gain more insights into biophysical aspects of temperature-controlled catheter ablation in humans. BACKGROUND: The electrode-tissue interface temperature and other biophysical parameters are among important variables determining the efficacy and safety of radiofrequency ablation of accessory pathways. Experimental studies have shown that radiofrequency-induced tissue necrosis can be accurately predicted by monitoring of catheter tip temperature. METHODS: 38 consecutive patients (14 f, 24 m; aged 42 +/- 12 years) with anterograde conducting accessory pathways (left sided: n = 22; right sided: n = 16) underwent temperature-controlled radiofrequency ablation (HAT 200S, Dr Osypka, Germany). The electrode temperature was monitored via a thermistor embedded into a 4 mm catheter tip. Power output was adjusted automatically during energy delivery in a closed loop system (preselected temp.: 70.1 +/- 5.8 degrees C). RESULTS: Accessory pathway conduction was successfully abolished in all patients after the delivery of 2.3 +/- 2.1 radiofrequency pulses (range: 1-9, median: 2). Interruption of the accessory pathway as evidenced by loss of preexcitation occurred after 5.9 +/- 5.4 s. At the time of the interruption of the accessory pathway the catheter tip temperature measured 54.2 +/- 11.2 degrees C in patients with left and 44.9 +/- 5.0 degrees C in patients with right sided accessory pathways, respectively (P < 0.008). Higher temperature levels during left sided applications did not shorten the time it took for the effect to appear (left sided accessory pathway: 7.5 +/- 6.3 s, right sided accessory pathway: 3.7 +/- 2.9 s; ns). The catheter tip temperature was significantly higher during left compared to right sided applications after 5 (52.1 +/- 3.1 degrees C vs 47.2 +/- 4.3 degrees C) and 10 s (61.5 +/- 6.2 degrees C vs 52.7 +/- 4.2 degrees C) following initiation of the impulse (P < 0.005). Power output and delivered energy did not differ significantly at the time of accessory pathway abolition. Peak values of delivered power (45.1 +/- 10.9 W vs 41.3 +/- 10.6 W; P < 0.05) and total delivered energy (2452 +/- 1335 J vs 1392 +/- 762 J; P < 0.02) were significantly higher in the group of right sided pathways compared to left sided applications. The peak temperature measured 77.1 +/- 13 degrees C during effective and 69.9 +/- 14 degrees C during ineffective energy applications (P < 0.05). The time it took for the effect to appear was significantly longer in transiently effective pulses (10.4 +/- 7.2 s) compared to permanently effective applications (5.9 +/- 5.4 s; P < 0.02). Despite temperature control, an abrupt rise in impedance was observed in 10 of 89 (11%) energy applications. No procedure-related complications occurred. CONCLUSIONS: Temperature-controlled radiofrequency ablation of manifest accessory pathways is highly effective and safe. The temperature response is faster and significantly higher in left-sided energy applications compared to right-sided pulses. Peak temperature levels measured at the electrode tip are significantly higher during effective than ineffective pulses. Sudden rises in impedance are not completely prevented during temperature-controlled radiofrequency ablation of accessory pathway, although no procedure-related complications were noted in this patient cohort.

Adult↗
PubMed1996

Temperature-controlled slow pathway ablation for treatment of atrioventricular nodal reentrant tachycardia using a combined anatomical and electrogram guided strategy.

AIMS: Anatomical and electrogram-guided techniques have been used separately for slow pathway ablation in atrioventricular nodal reentrant tachycardia. The aims of the present study were to analyse electrogram characteristics of target sites and biophysical parameters using a combined anatomical and electrogram-guided technique for temperature-controlled radiofrequency catheter ablation of the slow pathway. METHODS AND RESULTS: Using a temperature-controlled (pre-selected 60 degrees C) catheter system, 53 patients with atrioventricular nodal reentrant tachycardia underwent slow pathway radiofrequency ablation. Mapping was started posteroseptally near the coronary sinus ostium and continued towards the midseptal area if needed. The longest and latest atrial electrograms with an atrioventricular ratio of < or = 0.5 were targeted. After a median of two pulses (mean 2.36 +/- 1.33), atrioventricular nodal reentrant tachycardia was rendered non-inducible in all patients without complications. Successful sites had longer atrial electrograms (78.8 +/- 9.8 vs 67.6 +/- 13.3 ms, P < 0.003) and larger ventricular electrogram amplitudes (92.4 +/- 51.2 vs 63.1 +/- 28.8 mV, P < 0.05) than the failed sites, but had a similar atrioventricular ratio, P-A interval and atrial electrogram amplitude. Overall, an atrial electrogram duration of > or = 70 ms was associated with effective radiofrequency delivery, with 86% sensitivity and 62% specificity. The achieved temperature maximum was 62.3 +/- 9.8 degrees C at successful and 58.8 +/- 9.0 degrees C at unsuccessful sites (ns). There was no significant difference between successful and unsuccessful applications with respect to power output, impedance and total delivery energy. During a pre-discharge study, three patients with inducible atrioventricular nodal reentrant tachycardia underwent a repeat ablation. During 12.3 +/- 2.5 (6-15) months of follow-up, three others had a clinical recurrence of atrioventricular nodal reentrant tachycardia. CONCLUSIONS: The combined approach for slow pathway ablation is highly effective, requiring a low number of radiofrequency pulses. Long atrial activation time seems to be the most powerful predictor of success. Similar catheter tip temperature levels during successful and unsuccessful radiofrequency applications indicate that suboptimal selection of target sites rather than ineffective heating due to poor catheter tissue coupling is responsible for unsuccessful energy delivery.

Adolescent↗
PubMed1996

Biphasic defibrillation using a single capacitor with large capacitance: reduction of peak voltages and ICD device size.

The volume of current implantable cardioverter defibrillators (ICD) is not convenient for pectoral implantation. One way to reduce the size of the pulse generator is to find a more effective defibrillation pulse waveform generated from smaller volume capacitors. In a prospective randomized crossover study we compared the step-down defibrillation threshold (DFT) of a standard biphasic waveform (STD), delivered by two 250-microF capacitors connected in series with an 80% tilt, to an experimental biphasic waveform delivered by a single 450-microF capacitor with a 60% tilt. The experimental waveform delivered the same energy with a lower peak voltage and a longer duration (LVLD). Intraoperatively, in 25 patients receiving endocardial (n = 12) or endocardial-subcutaneous array (n = 13) defibrillation leads, the DFT was determined for both waveforms. Energy requirements did not differ at DFT for the STD and LVLD waveforms with the low impedance (32 +/- 4 omega) endocardial-subcutaneous array defibrillation lead system (6.4 +/- 4.4 J and 5.9 +/- 4.2 J, respectively) or increased slightly (P = 0.06) with the higher impedance (42 +/- 4 omega) endocardial lead system (10.4 +/- 4.6 J and 12.7 +/- 5.7 J, respectively). However, the voltage needed at DFT was one-third lower with the LVLD waveform than with the STD waveform for both lead systems (256 +/- 85 V vs 154 +/- 51 V and 348 +/- 76 V vs 232 +/- 54 V, respectively). Thus, a single capacitor with a large capacitance can generate a defibrillation pulse with a substantial lower peak voltage requirement without significantly increasing the energy requirements. The volume reduction in using a single capacitor can decrease ICD device size.

Adult↗
PubMed1996

Improved sensing signals after endocardial defibrillation with a redesigned integrated sense pace defibrillation lead.

Adequate sensing is a basic requirement for appropriate therapy with ICDs. Integrated sense pace defibrillation leads, which facilitate ICD implantation, show a close proximity of sensing and defibrillation electrodes that might affect the sensing signal amplitude by the high currents of internal defibrillation. In 99 patients, we retrospectively examined two integrated sense pace defibrillation leads, either both with a distance of 6 mm between the tip of the lead (sensing cathode) and the right ventricular defibrillation electrode (sensing anode) or one with a distance of 12 mm. Three seconds after a shock of 20 J, mean sensing signal amplitude during sinus rhythm (SR) decreased from 10.5 +/- 4.3 mV to 5.1 +/- 3.7 mV (P < 0.001) for the 6-mm lead, but showed no significant decrease for the 12-mm lead. The degree of signal reduction was inversely related to the time passed since defibrillation. Significant differences in reduction of sensing signal amplitude concerning monophasic and biphasic shocks could not be observed. Mean sensing signal amplitude of VF after shocks that failed to terminate it decreased in the same order as during SR (from 8.3 +/- 4.1 mV to 4.1 +/- 3.2 mV), but resulted in no failure of redetection during ongoing VF. DFTs did not differ for the 6-mm and the 12-mm lead. In conclusion, close proximity of the right ventricular defibrillation coil to the sensing tip of an integrated sense pace defibrillation lead causes energy and time related reduction in sensing signal amplitude after defibrillation, and might cause undersensing in the postshock period. A new lead design with a more proximal position of the right ventricular defibrillation coil avoids these problems without impairing DFTs.

Defibrillators, Implantable↗
PubMed1996

Variants of preexcitation--specialized atriofascicular pathways, nodofascicular pathways, and fasciculoventricular pathways: electrophysiologic findings and target sites for radiofrequency catheter ablation.

INTRODUCTION: In the present report, the electrophysiologic findings in patients with different types of variants of preexcitation, i.e., atriofascicular, nodofascicular, and fasciculoventricular fibers, and the results of radiofrequency catheter ablation using different target sites are described. METHODS AND RESULTS: Twelve patients (mean age 36 +/- 17 years) with variants of the preexcitation syndromes underwent electrophysiologic study and radiofrequency catheter ablation. The atrial origin of atriofascicular pathways remote from the normal AV node was assessed by application of late atrial extrastimuli that advanced ("reset") the timing of the next QRS complex without anterograde penetration into the AV node. In patients with atriofascicular pathways, ablation of the accessory pathway or the retrograde fast AV node pathway was attempted. Ablation of the atriofascicular pathways was guided by a stimulus-delta wave interval mapping in the first five patients and by recording of atriofascicular pathway activation potentials in the next five patients. A nodofascicular pathway was suggested if VA dissociation occurred during tachycardia and if atrial extrastimuli failed to reset the tachycardia without anterograde penetration into the AV node. A fasciculoventricular connection was suggested if the proximal insertion of the accessory pathway was found to arise from the His bundle or bundle branches. The PR interval was expected within normal limits during sinus rhythm and the QRS complex to be slightly prolonged with a discrete slurring of the R wave, suggesting a small delta wave. Ten of the 12 patients had evidence for atriofascicular pathways and one patient each for a nodofascicular and fasciculoventricular pathway. In six patients, the atriofascicular pathways were successfully ablated, and in two patients, the retrograde fast AV node pathway. In one patient, a concealed right posteroseptal accessory AV pathway served as the retrograde limb and was successfully ablated. The nodofascicular pathway was shown to be a bystander during AV node reentrant tachycardia. After successful fast AV node pathway ablation resulting in marked PR prolongation, no preexcitation was present during sinus rhythm because of the proximal insertion of the nodofascicular pathway distal to the delay producing parts of the AV node. The proximal insertion of the fasciculoventricular pathway was suggested to arise distal to the AV node at the site of the penetrating AV bundle. The earliest ventricular activation at the His-bundle recording site indicated the ventricular insertion of this accessory connection into the ventricular summit. The fasciculoventricular connection gave rise to a fixed ventricular preexcitation and served as a bystander during orthodromic AV reentrant tachycardia incorporating a left-sided accessory AV pathway. CONCLUSION: The majority of patients with variants of the preexcitation syndrome present with specialized atriofascicular pathways that seem to originate from remnants of the specialized AV ring tissue. Nodofascicular and fasciculoventricular pathways exist and may give rise to preexcitation, although their functional role in participation of clinical arrhythmias still needs to be elucidated. In the present study, both a fasciculoventricular pathway and a nodofascicular pathway acted as a bystander.

Adolescent↗
PubMed1996

Catheter ablation of incessant ventricular tachycardia.

Emergency catheter ablation of ventricular tachycardia was performed in 22 patients. All patients had incessant ventricular tachycardia that persisted for > or = 12 h/day and was only transiently terminated by stimulation techniques, anti-arrhythmic drugs or cardioversion. Radiofrequency catheter ablation was carried out using entrainment criteria as well as endocardial activation mapping. Ventricular tachycardia was terminated in 91% of cases, one patient underwent map-guided surgery and the remaining patient was managed by anti-arrhythmic drugs. After the initial ablation procedure 3 of the 20 patients who could be acutely managed died in hospital: one patient in refractory heart failure 24 h following ablation, one patient suddenly 10 days following ablation on the ward and another patient 4 weeks following ablation because of septicemia. Four patients underwent elective implantation of a cardioverter-defibrillator because of inducible ventricular tachycardia, and another patient underwent elective map-guided surgery. Overall, 12 patients were discharged without any additional non-pharmacologic intervention; 5 of them were free of anti-arrhythmic drugs and 7 patients had previously received ineffective medication including continuation of amiodarone in 3 patients. These results indicate that radiofrequency catheter ablation may play a role in the treatment of patients with incessant ventricular tachycardia. Thus, non-pharmacologic management of incessant ventricular tachycardia is associated with a high hospital mortality rate especially in surgically treated patients. Catheter ablation using radiofrequency current is the preferred approach for acute palliation.

Catheter Ablation↗
PubMed1996

[Methods of catheter ablation in ventricular tachycardic arrhythmias].

Catheter ablation has evolved as the therapy of choice in patients with atrioventricular nodal reentrant tachycardia or atrioventricular tachycardia involving accessory pathways. Radiofrequency current catheter ablation is now generally accepted and most frequently used. In patients with ventricular tachycardia and no organic heart disease (idiopathic ventricular tachycardia) the success rates range between 80-90%. In addition, in patients with bundle branch reentrant tachycardia up to 100% success rates are described. The usefulness of radiofrequency ablation in patients with structural heart disease is still controversial. Although in patients with incessant ventricular tachycardia high acute success rates are observed, the results in post-myocardial infarction tachycardia or dilative cardiomyopathy range only between 40 and 75%. Further refinement of localization techniques as well as improvement of ablation technology is mandatory until the routine use of this technique as a curative procedure for ventricular tachycardia is defined.

Atrioventricular Node↗
PubMed1996

[Pharmacologic therapy of ventricular tachyarrhythmias: value of class III anti-arrhythmia drugs].

Treatment strategies in patients with life-threatening ventricular tachyarrhythmias (i.e. sustained ventricular tachycardia, ventricular fibrillation, aborted sudden cardiac death) are changing. Amiodarone and d,l-sotalol, chosen by electrophysiologic study guidance, can be considered as drugs of choice for the pharmacological treatment. Compared to these agents, which both have additional electrophysiologic effects, the new pure class III agents seem to be less effective. With regard to antiarrhythmic efficacy, clinical trials comparing the long-term efficacy of antiarrhythmic agents and the implantable cardioverter/defibrillator are under way. Preliminary results indicate that the implantable cardioverter/defibrillator may provide superior outcome with regard to sudden cardiac death compared to the use of class III agents.

Amiodarone↗
PubMed1995

Radiofrequency catheter ablation of sustained ventricular tachycardia in idiopathic dilated cardiomyopathy.

BACKGROUND: The feasibility of radiofrequency (RF) catheter ablation for the treatment of sustained ventricular tachycardia (VT) in patients with coronary artery disease and remote myocardial infarction has recently been demonstrated. At present, therapeutic options for VT in patients with idiopathic dilated cardiomyopathy (DCM) include antiarrhythmic drugs and implantable cardioverter/defibrillators (ICD). The purpose of the present study was to investigate the feasibility of RF catheter ablation in patients with idiopathic DCM who could not be adequately treated by conventional treatment modalities because of incessant or frequent, recurrent VT. METHODS AND RESULTS: RF current application for ablation of 9 VTs (mean cycle length, 402 +/- 78 ms) was attempted in 8 patients with idiopathic DCM (4 men, 4 women; mean age, 54 +/- 6 years; mean left ventricular ejection fraction, 30 +/- 9%). Inclusion criteria for ablation were incessant VT (n = 4) or frequent, recurrent VT reproducibly inducible with programmed electrical stimulation (n = 5). Three patients had suffered aborted sudden cardiac death, and 2 had experienced syncope. Two patients were artificially ventilated and catecholamine dependent for hemodynamic reasons at the time of attempted ablation. Potential target sites for RF current application were identified by detailed endocardial mapping during sinus rhythm, activation and entrainment mapping during VT, and pace mapping. After 7 +/- 5 RF pulses (range, 2 to 18 pulses; median, 6 pulses) applied with 32 +/- 7 W for 39 +/- 9 seconds, 6 of the 9 target VTs (67%) were rendered noninducible (4 of 4 incessant VTs and 2 of 5 chronic recurrent VTs). In 6 patients, VTs with ECG morphologies other than the target VTs were inducible after RF catheter ablation. Seven patients were on antiarrhythmic drugs during the ablation procedure and during the follow-up period of 8 +/- 5 months (range, 2 to 17 months). One patient received an ICD before RF ablation, 4 patients after RF ablation, and 1 patient after ablation of an incessant VT and before attempted ablation of frequent, recurrent VTs. One patient underwent heart transplantation 5 months after ablation in end-stage heart failure. There were no acute complications during the mapping and ablation procedure. During the follow-up period, 1 patient had been resuscitated from ventricular fibrillation 6 weeks after ablation and finally died of congestive heart failure 2 weeks later. No further episodes of incessant VT occurred in the patients who had undergone RF current application for ablation of incessant VT. A complete prevention of VT could be achieved in 2 of 8 patients, whereas in 5 patients, VT episodes were stored in the ICD devices during follow-up. CONCLUSIONS: The results of the present study indicate that RF current application for ablation of VT in a select group of patients with idiopathic DCM is feasible. The efficacy of RF ablation may be high in patients presenting with incessant VT, whereas the success rate seems to be only moderate in patients with chronic recurrent VT. In all patients, additional treatment options, including antiarrhythmic drugs, ICDs, and/or heart transplantation, were applied after RF ablation, indicating that RF ablation for this indication may be an adjunctive and not a curative treatment option.

Anti-Arrhythmia Agents↗
PubMed1995

Are there gender differences in patients with coronary artery disease presenting with spontaneous sustained ventricular tachycardia and ventricular fibrillation?

The incidence of coronary artery disease (CAD) is greater in men than in women. The aim of the study was to analyze whether any gender-related differences in patients with CAD and documented spontaneous sustained ventricular tachyarrhythmias exist, and which parameters influence the induction of sustained ventricular tachyarrhythmias. The data of 250 patients [43 women (17.2%) and 207 men (82.8%)] with spontaneous sustained ventricular tachycardia [n = 190 (76%)] and fibrillation [n = 60 (24%)] who underwent coronary and left ventricular angiography, electrophysiological study, and signal-averaging electrocardiogram (ECG) form the basis of this analysis. No gender-related differences could be observed in age, number of diseased coronary arteries, history, location and number of myocardial infarctions, presence of left ventricular aneurysm, ejection fraction, type of spontaneous or induced arrhythmias, right ventricular effective refractory period, and signal-averaged ECG parameters. Age, presence of previous myocardial infarction, and ejection fraction were significant predictors (p < 0.001) of inducibility of sustained ventricular tachyarrhythmias. Once CAD has begun, female and male patients present similar clinical and electrophysiologic characteristics. Thus, both genders should benefit similarly from diagnostic and therapeutic approaches if they are referred to the hospital or to invasive interventions at similar intervals in the course of their illness.

Age Factors↗
PubMed1995

Molecular analysis at the Harvey Ras-1 gene in patients with long QT syndrome.

Patients with long QT syndrome (LQTS; MIM 1921500) frequently suffer from syncope and are threatened by sudden cardiac death due to ventricular arrhythmias, typically of the torsade de pointes type. Initial progress in revealing the molecular basis of the disease was made by the observation of genetic linkage of the disease locus to the Harvey Ras-1 gene (HRAS 1) on chromosome 11p15.5. More recently loci on chromosomes 3, 4, and 7 have also been found to be linked to LQTS, thus demonstrating heterogeneity in the causes for this disease. The present study performed sequence analysis on the HRAS 1 gene in patients with congenital and acquired LQTS to determine the frequency of HRAS 1 mutations in patients with this disease. In neither group were no mutations identified in the coding regions or in the splice donor and acceptor sites. Alleles characterized by a T to C transition in exon 1 and an insertion/deletion polymorphism upstream of exon 1 showed no significant difference in their frequencies between LQTS patients and normal controls. No quantitative influence of the such characterized genotypes on the QT duration was observed. These results demonstrate that structural mutations in the HRAS 1 gene are not a frequent cause of LQTS. Also, since there was no association of different alleles at the HRAS 1 locus with changes in QT duration, it appears unlikely that this gene is a major contributor to this disease.

Alleles↗
PubMed1995

Electrophysiologic effects of potassium channel openers.

Potassium-channel openers or activators have been introduced as a new class of antihypertensive and antianginal agents that act by increasing membrane conductance to potassium, mainly through augmentation of the ATP-sensitive potassium current. Recent in vitro studies have shown that K(+)-channel openers exert concentration-dependent effects on cardiac electrophysiology. A shortening of the cardiac action potential by acceleration of repolarization has been reported in multicellular preparations as well as in isolated myocytes. However, drug concentrations that affect the action potential duration of myocardial cells are considerably higher (10- to 100-fold) than those needed for effects on vascular smooth muscle cells. Studies in which mostly high concentrations of K(+)-channel openers were used have demonstrated that these drugs may accelerate automaticity and may promote reentrant activity. Particular interest has focused on the question whether opening of potassium channels may be potentially arrhythmogenic in the setting of acute myocardial ischemia. On the other hand, recent studies have shown that K(+)-channel openers are effective in suppressing polymorphic ventricular tachyarrhythmias induced by early afterdepolarizations and triggered activity in vivo. The clinical relevance of these experimental studies to the clinical situation is still unclear. Some K(+)-channel openers have been shown to produce electrocardiographic T-wave changes in patients in whom their effectiveness as antihypertensives was tested. However, this effect was not associated with adverse effects and has not been demonstrated for all compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Localization and radiofrequency catheter ablation of left-sided accessory pathways during atrial fibrillation. Feasibility and electrogram criteria for identification of appropriate target sites.

OBJECTIVES: The purpose of the present study was to assess the feasibility of and electrophysiologic criteria for successful radiofrequency catheter ablation of left-sided accessory pathways during atrial fibrillation in patients with Wolff-Parkinson-White syndrome. BACKGROUND: The onset of recurrent or sustained atrial fibrillation can complicate or significantly prolong accessory pathway catheter ablation procedures. METHODS: We studied 19 consecutive patients (mean age [+/-SD] 44 +/- 16 years) with Wolff-Parkinson-White syndrome who had ongoing atrial fibrillation with rapid anterograde conduction over the accessory pathway (mean ventricular rate [+/-SD] 173 +/- 26 beats/min, range 130 to 220) at the beginning of the localization procedure during radiofrequency catheter ablation. Localization and ablation of the accessory pathway were performed with a 7F deflectable catheter (4-mm tip) that was placed underneath the mitral valve annulus. The electrophysiologic criteria from unipolar and bipolar local electrograms were compared for successful (n = 18) and unsuccessful (n = 39) sites. RESULTS: The accessory pathways were localized in the left posteroseptal (n = 6), posterior (n = 1), posterolateral (n = 7) and lateral (n = 5) regions and successfully ablated during atrial fibrillation in 18 (95%) of 19 patients with a mean of 3 +/- 2 radiofrequency pulses (range 1 to 8, median 2). Presence of an accessory pathway potential (94% vs. 44%), early activation time of the ventricular electrogram (-3.2 +/- 9.2 vs. -15.3 +/- 12.6 ms) and recording of atrial activation (88% vs. 61%) from the ablation catheter were helpful in identifying successful sites (p < 0.001, p < 0.001 and p < 0.05, respectively, compared with unsuccessful sites). In addition, the ventricular activation time in relation to the intrinsic deflection of the unipolar electrogram was significantly earlier at successful than unsuccessful sites (18.1 +/- 4.8 vs. 24.4 +/- 6.6 ms, p < 0.01). A QS complex on the unipolar electrogram was observed at 96% of successful sites and at 94% of unsuccessful sites (p = 0.74). Multivariate logistic regression analysis revealed that the presence of an accessory pathway potential (p < 0.002) and early ventricular activation time in relation to the onset of the QRS complex (p < 0.001) were independent predictors of ablation success. CONCLUSIONS: Localization and radiofrequency catheter ablation of left-sided accessory pathways is possible in patients with sustained atrial fibrillation and rapid anterograde conduction over the accessory pathway during the ablation procedure. The electrophysiologic criteria described here can be used to reliably identify successful sites for radiofrequency ablation.

Adult↗