[Drug therapy of cardiac arrhythmias].
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Biomedical subjects
Publications and source records attributed to T Lewalter.
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UNLABELLED: The high prevalence of atrial fibrillation (AF) and its clinical complications, the poor efficacy of medical therapy for preventing recurrences, and dissatisfaction with alternative modes of therapy stimulated interest in implantable atrial and combined atrioventricular defibrillators. In a multicenter study, the safety and efficacy of a stand alone implantable atrial defibrillator, the Metrix system, were evaluated. The device was implanted in 51 patients with highly symptomatic episodes of AF refractory to pharmacological treatment. During a follow-up of 9 months, 96% of 227 spontaneous AF episodes were successfully converted to sinus rhythm in 41 patients. In 62 episodes (27%), several shocks and/or additional drug treatment were required to maintain stable sinus rhythm because of early recurrences of AF. A total of 3719 shocks were delivered and no induction of ventricular proarrhythmia or inaccurately synchronized shocks occurred. The AF detection algorithm exhibited a 100% specificity for the recognition of sinus rhythm and a 92.3% sensitivity for the detection of AF. The combined atrioventricular defibrillator, Jewel AF 7250, was evaluated in a multicenter, randomized, cross-over trial. The primary study objectives included: overall safety as determined by complications-free survival at 6 months, efficacy of tiered atrial pacing and defibrillation therapies for termination of spontaneous atrial tachycardias (AT) and AF, and relative sensitivity of a new dual-chamber detection algorithm. The device was implanted in 211 patients with either a history of ventricular tachyarrhythmias (VT/VF) alone or with a history of both AT/AF and VT/VF. During a mean follow-up of 4.5 months, it has been shown that the Jewel AF is safe and effective in treating atrial and ventricular tachyarrhythmias. Pace termination of 85% of AT episodes were achieved with painless delivery of antitachycardia pacing; additional 35% of AT episodes were terminated by high frequency burst pacing. CONCLUSIONS: The stand alone implantable atrial defibrillator may be safe and clinically useful in selected patients for the treatment of highly symptomatic, drug resistant recurrences of AF. The combined atrioventricular defibrillator may be particularly indicated in patients presenting with both a history of atrial and ventricular tachyarrhythmias.
Radiofrequency catheter ablation of typical atrial flutter at the isthmus between the tricuspid annulus and the inferior vena cava is established. However in selected patients, the creation of a continuous linear lesion at the targeted isthmus requires a lengthened procedure or is not feasible at all and atrial flutter recurrences are common. In a retrospective analysis, we found that an intraoperatively determined distance between the tricuspid annulus and the inferior vena cava of <.2.5 cm is an independent predictor of a lengthened or failed ablation procedure. Additional equipment, e.g., long introducer sheaths, adapted ablation catheter design, or irrigated tip ablation, as well as alternative ablation approaches, e.g., linear lesions between the tricuspid annulus and Eustachian ridge, have been invented in order to increase the acute success rate or decrease fluoroscopy and procedure time. In a prospective study on the effects of various conduction properties at the isthmus between tricuspid annulus and inferior vena cava following radiofrequency ablation of atrial flutter, we showed previously that others than a complete bidirectional conduction block predicts a high recurrence rate of atrial flutter. For determination of transisthmal conduction properties following ablation, established mapping approaches are documentation of double potentials at the ablation line and right atrial activation sequence following posteroseptal and low lateral right atrial pacing. Novel threedimensional mapping systems, i.e., Carto(R) and EnSite(R), may further enhance the accuracy of conventional mapping techniques.
AIMS: Although bipolar sensing is recommended and desirable in patients with dual chamber pacemakers (DDD) and intermittent atrial fibrillation (AF) it is a clinical reality that some patients who are given unipolar atrial leads without a prior history of AF may develop intermittent AF during follow-up. It was therefore the purpose of this prospective study to compare the electrogram amplitudes of AF potentials with sinus rhythm P-wave potentials as a relevant factor for appropriate mode switching in dual chamber pacing with unipolar atrial sensing. METHODS AND RESULTS: Forty-two patients with dual chamber pacemakers, unipolar atrial leads and intermittent AF were studied. Aside from measuring the P-wave potential, it was possible in 14 patients (4 women, 10 men; mean age: 61.8 (+/- 13.3) years) additionally to document spontaneous AF electrogram potentials using pacemaker telemetry. A prospective survey study was performed including a 6 month follow-up period with an outpatient clinic visit every 2-3 weeks. The mean P-wave electrogram amplitude was 3.4 (+/- 1.8) mV (range: 1.4-7.4) compared with the mean amplitude during AF of 2.04 (+/- 1.26) mV (range: 0.8-5.2 mV) indicating a significant attenuation of 40% during AF (P < 0.0001). A linear correlation regression analysis revealed that there was a significant correlation between the P-wave and the AF amplitude (P < 0.0001), with a correlation coefficient of r = 0.867. CONCLUSION: Once it is known that a substantial reduction exists in electrogram amplitude, compared with the P wave electrogram potential, an estimate can be made of whether AF potentials will be sensed, if the programming of atrial sensitivity is congruent with the P-wave characteristics and the presence or absence of myopotential triggering.
Internal atrial defibrillation (IAD) is able to restore sinus rhythm in patients with chronic atrial fibrillation (AF) and failed external electrical and/or pharmacologic cardioversion. To assess whether cardiorespiratory and hemodynamic function improve after IAD, 35 patients were prospectively investigated during constant workload exercise by spiroergometry and Doppler echocardiography before IAD, and 1 day and 1 month after IAD. Oxygen uptake kinetics, ventilation, left atrial mechanical function, and pulmonary artery pressure were determined simultaneously at rest and during steady state. During the serial follow-up, 20 patients maintained sinus rhythm. The time interval for achieving the steady state (146 +/- 53 vs 132 +/- 42 seconds; p = 0.5) and the oxygen deficit (645 +/- 190 vs 670 +/- 174 ml; p = 0.7) were not different before and 1 day after IAD, but decreased significantly after 1 month (98 +/- 16 seconds, p = 0.01 and 487 +/- 72 ml, p = 0.02). Exercise pulmonary artery systolic pressures were 38 +/- 13 mm Hg before IAD, increased significantly to 46 +/- 11 mm Hg on day 1 (p = 0.03), and decreased below baseline values at 1 month to 31 +/- 12 mm Hg (p = 0.07). Peak A-wave velocities increased from 0.51 +/- 0.1 m/s after 1 day to 0.67 +/- 0.2 m/s after 1 month (p = 0.03). Restoration of sinus rhythm in patients with AF resistant to external electrical and/or pharmacologic cardioversion improves hemodynamic and cardiorespiratory function at daily activity exercise levels.
In selected patients, atrial fibrillation (AF) converts to atrial flutter (AFI) due to treatment with class IC antiarrhythmic drugs. In this study, we prospectively investigated the effects of AFI ablation and continuation of drug therapy in patients with AF who developed AFI due to long-term administration of class IC antiarrhythmic drugs. The study population consisted of 187 patients from an AF registry with paroxysmal AF who were orally treated with flecainide (n = 96) or propafenone (n = 91). Twenty-four patients (12.8%) developed AFI during the course of treatment. In 20 of these patients (10.7%), electrophysiologic study revealed typical AFI. These patients underwent radiofrequency ablation of AFI. Ablation failed in 1 patient. All patients continued preexisting drug treatment. Recurrence of AF was assessed by ambulatory Holter monitoring and serial questionnaires. During a mean follow-up of 11 +/- 4 months, the incidence of AF episodes was significantly lower in patients with a combined therapy (2.7 +/- 3.6 per year) than in control subjects with a sole drug treatment (7.8 +/- 9.2 per year, p <0.05) and than before therapy (10.2 +/- 5.4 per year, p <0.001). Subgroup analysis revealed that 7 patients (36.8%) remained symptom free with no evidence of atrial tachyarrhythmia. Eight additional patients (42.1%) had ongoing paroxysmal AF, however, with a significantly lower incidence of AF episodes than before therapy (2.3 +/- 1.6 per year vs 11.5 +/- 5.0 per year, p <0.001). In the remaining 4 patients (14.7%), no beneficial effect of AFI ablation was found. It is concluded that in patients with AF who develop typical AFI due to administration of class IC antiarrhythmic agents, a combined therapy with catheter ablation of AFI and continuation of drug treatment is highly effective in reducing occurrence and duration of atrial tachyarrhythmias.
OBJECTIVES: In this study, the transverse conduction capabilities of the crista terminalis (CT) were determined during pacing in sinus rhythm in patients with atrial flutter and atrial fibrillation. BACKGROUND: It has been demonstrated that the CT is a barrier to transverse conduction during typical atrial flutter. Mapping studies in animal models provide evidence that this is functional. The influence of transverse conduction capabilities of the CT on the development of atrial flutter remains unclear. METHODS: The CT was identified by intracardiac echocardiography. The atrial activation at the CT was determined during programmed stimulation with one extrastimulus at five pacing sites anteriorly to the CT in 10 patients with atrial flutter and 10 patients with atrial fibrillation before and after intravenous administration of 2 mg/kg disopyramide. Subsequently, atrial arrhythmias were reinduced. RESULTS: At baseline, pacing with longer coupling intervals resulted in a transverse pulse propagation across the CT. During shorter coupling intervals, split electrograms and a marked alteration of the activation sequence of its second component were found, indicating a functional conduction block. In patients with atrial flutter, the longest coupling interval that resulted in a complete transverse conduction block at the CT was significantly longer than that in patients with atrial fibrillation (285 +/- 49 ms vs. 221 +/- 28 ms; p < 0.05). After disopyramide administration, a transverse conduction block occurred at longer coupling intervals as compared with baseline (287 +/- 68 ms vs. 250 +/- 52 ms; p < 0.05). Subsequently, a sustained atrial arrhythmia was inducible in 15 of 20 patients. This was atrial flutter in three patients with previously documented atrial fibrillation and in eight patients with history of atrial flutter. Mapping revealed a conduction block at the CT in all of these patients. CONCLUSIONS: It was found that the CT provides transverse conduction capabilities and that the conduction block during atrial flutter is functional. Limited transverse conduction capabilities of the CT seem to contribute to the development of atrial flutter.
The oxygen uptake to work rate (VO2/WR) relationship observed throughout peak exercise testing is already being applied for rate adaptive pacemaker programming. However, the detailed curve design of VO2/WR with respect to the anaerobic threshold (AT) has not yet been investigated. It was the purpose of this study to determine the VO2/WR slope below and above the AT in a healthy control group. Seventy-eight healthy control subjects (45.9 +/- 17.4 years; 34 women: 49.9 +/- 18.6 years 44 men: 43.6 +/- 16.6 years) were exercised on a treadmill with "breath-by-breath" gas exchange monitoring using the symptom limited "ramping incremental treadmill exercise" (RITE) protocol. The slope of the VO2/WR relationship from rest to peak exercise (r-p), rest to AT (slope A), and AT to peak exercise (slope B) in mL oxygen uptake per watt of external treadmill work was determined by linear regression analysis. [table: see text] The oxygen uptake to work rate relationship throughout peak exercise in the entire study group generated a significant slope change at the AT (31%, P < 0.0001) with a decreasing slope during higher work load intensities. Female subjects demonstrated a greater percentage of slope change at AT (43%), as compared to men (22%, P < 0.01). When using the oxygen uptake to work rate relationship for the programming of the pacemaker's rate response to exercise, the significant slope change at the AT should be considered to more appropriately pace during higher work intensities supported by anaerobic metabolism. Female pacemaker patients should be programmed to generate a steeper VO2/WR slope below AT with a greater slope change at AT, as compared to men. Abnormally high oxygen uptake to work rate ratios above the AT may be possibly used as an indicator of overpacing.
INTRODUCTION: Creation of linear lesions is an established ablation goal. Verification of complete conduction block at the ablation line is required to determine ablation success. Conventional mapping techniques are sequential endocardial activation mapping and documentation of double potentials. Recently, a noncontact multielectrode array catheter was developed that allows instantaneous three-dimensional mapping by simultaneous reconstruction of > 3,000 electrograms. In this study, we prospectively compared the accuracy of noncontact mapping to identify discontinuities in linear lesions and to verify a conduction block with that of conventional mapping techniques. METHODS AND RESULTS: In 12 patients with atrial flutter, radiofrequency pulses were applied between the tricuspid annulus and either the inferior vena cava or the eustachian ridge. Following each application, pulse propagation at the ablation line was determined during pacing by conventional mapping techniques. The findings were compared to high-density isopotential mapping using the noncontact multielectrode array catheter. It was found that noncontact mapping reliably distinguished conduction delays from a conduction block as defined by contact mapping. In addition, noncontact mapping instantaneously identified the area where a discontinuity in the line of block was present. In these patients, complete conduction block was achieved by radiofrequency pulses guided by the noncontact mapping system. CONCLUSION: Noncontact mapping is highly accurate in distinguishing conduction delays from a complete conduction block. By providing an instantaneous high-density propagation vector at all sites along the ablation line, three-dimensional isopotential mapping is helpful in localizing discontinuities of linear lesions and, thus, may facilitate the creation of a complete conduction block.
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Electrocardiographic and clinical characteristics are currently used as diagnostic criteria for the long QT-syndrome. In borderline electrocardiographic findings associated with unclear syncope, it is often difficult to ensure or exclude long QT-syndrome. Schwartz and coworkers therefore created a point system as a guide in clinical decision making. In recent years genetic diagnostics have entered the arena of long-QT assessment. Aside from new insights into the pathophysiology of the long QT-disorder, it is expected that genetic diagnostics will offer substantial help to ascertain long QT-syndrome in patients with borderline electrocardiographic and clinical findings and improve risk stratification in long-QT family members. Performing linkage analysis, coupling of autosomal-dominant congenital long QT-syndrome (Romano-Ward Syndrome) to chromosomes 11 (LQT1/11p15.5), 3 (LQT3/3p21), 7 (LQT2/7q35), and 4 (LQT4/4q25-27) was demonstrated. More recently, the disease genes in long QT-syndrome 1, 2, and 3 could be identified. Analysis of the base-pair sequence allowed detection of several different mutations in different families illustrating genetic heterogeneity. Aside from diagnostic aspects, molecular genetics may also guide pharmacological therapy by identifying the specific ion-channel disorder leading to QT-prolongation and sudden death.
PURPOSE: Right ventricular dysplasia (RVD) represents an important cause of sudden death and ventricular arrhythmias in young patients. The aim of this study was to describe diagnostic diagnostic criteria and the MR-tomographie aspects of the disease. METHODS: 34 patients with clinically suspected RVD were examined by 0.5-T MRI (cardiac-gated T1-weighted spin echo sequences and cine gradient echo sequences). RVD was confirmed in 16 patients and ruled out in 18 patients. MR images were evaluated for presence of: 1. right myocardial fatty infiltration, 2. dilatation of the right ventricle, 3. dilatation of the right ventricular outflow tract, and 4. localised right ventricular aneurysm. RESULTS: Right myocardial fatty infiltration was detected by MRI in 11 of 16 patients (69%) with RVD. Dilatation of the right ventricle was seen in 5 patients, dilatation of the right outflow tract in one patient, and localised right ventricular aneurysm in two patients with RVD. CONCLUSIONS: MRI is able to demonstrate fatty replacement of right ventricular myocardium in most cases and plays an important role in the diagnosis of RVD.
INTRODUCTION: Bidirectional conduction block at the subeustachian isthmus predicts long-term efficacy of atrial flutter ablation. Limited data are available on the incidence and outcome of minor conduction changes such as unidirectional or incomplete block. This prospective study sought to systematically assess discrete acute and long-term alterations of bidirectional conduction prior to a complete conduction block. METHODS AND RESULTS: In 41 patients with type I atrial flutter, pulse propagation through the subeustachian isthmus during low lateral and proximal coronary sinus pacing was documented and analyzed following each consecutive radiofrequency (RF) application. In cases of altered conduction properties and noninducibility of atrial flutter, patients were followed-up for 12 months. Three sets of results were found. First, following RF application, 23 patients presented a progressive conduction delay prior to a complete conduction block. Second, RF application did not always affect counterclockwise and clockwise conduction simultaneously or to the same extent. In 13 patients, an initial alteration of counterclockwise conduction was present before an alteration of clockwise conduction; in 5 patients, clockwise conduction was primarily affected. Third, the recurrence rate of typical atrial flutter was 9% (2/22) in patients with a complete bidirectional conduction block, 54% (7/13) in patients with unidirectional conduction block, and 100% (6/6) in patients with sole bidirectional conduction delay. CONCLUSION: In 50% of the patients, consecutive RF applications resulted primarily in a progressive conduction delay rather than a sudden conduction block. Since counterclockwise and clockwise conduction were not always affected simultaneously or to the same extent, lateral as well as septal pacing is recommended for improvement of bidirectional conduction block. Normalization of primarily altered conduction and, therefore, recurrence of atrial flutter are high in all patients without bidirectional block.
Atrial flutter can be understood as atrial tachycardia due to a single intra-atrial macroreentrant circuit that is determined by fixed or functional boundaries. In various types of atrial flutter, radiofrequency ablation has become an established curative therapy. During the course of an ablation procedure, five steps can be distinguished: (1) determination of the reentrant circuit; (2) identification of the boundaries; (3) proof of the participation of an isthmus between the boundaries in the reentrant circuit; (4) connection of the barriers by a linear lesion; and (5) proof that the line of block is complete. After establishing these five steps, the acute and long-term results of atrial flutter ablation are comparable to those of other supraventricular tachycardias. In this review, we discuss these principles of atrial flutter ablation with an emphasis on typical atrial flutter.
INTRODUCTION: Internal atrial defibrillation has been evaluated as an alternative approach to the external technique for more than two decades. Previous studies in animals and humans have shown that internal atrial defibrillation is feasible with relatively low energies. The promising results achieved with internal atrial defibrillation have facilitated the development of an implantable atrial defibrillator (IAD). METHODS AND RESULTS: For any new therapy, it is imperative to demonstrate safety, efficacy, tolerability with improvement in quality of life, and cost-effectiveness compared with therapeutic options already available. Maintenance of sinus rhythm or prolonged duration in arrhythmia-free intervals should be demonstrated clearly with an IAD. Initial clinical experience with the Metrix system indicates stable atrial defibrillation thresholds, appropriate R wave synchronization markers, no shock-induced ventricular proarrhythmia, and excellent detection of atrial fibrillation (AF) with a specificity of 100%. Ventricular proarrhythmia has not been reported for correctly R wave synchronized low-energy shocks when closely coupled to RR intervals, and long-short cycles are avoided. CONCLUSION: Preliminary experience with the Metrix system suggests that the IAD may offer a therapeutic alternative for a subgroup of patients with drug-refractory, symptomatic, long-lasting, and infrequent episodes of AF. Further efforts must be undertaken to reduce the patient discomfort associated with internal atrial defibrillation in an attempt to make this new therapy acceptable to a larger patient population with AF.
OBJECTIVE: To establish a normal database for oxygen uptake (VO2) kinetics during low intensity treadmill exercise (LITE) testing, to be used as a guideline for programming rate adaptive pacemakers, and to determine its relation to VO2 at anaerobic threshold and peak exercise. DESIGN: VO2 kinetics during LITE were compared with VO2 at anaerobic threshold and at peak exercise. SETTING: LITE testing is applicable during ambulatory or hospital care and can even be performed by patients with reduced cardiac capacity. PATIENTS: 60 healthy subjects (23 women, 51.6 (SD 20.4) years; 37 men, 42.2 (16.2) years). INTERVENTIONS: Treadmill exercise testing with "breath by breath" gas exchange monitoring using the LITE protocol for steady state, submaximal exercise, and the ramping incremental treadmill exercise (RITE) protocol for peak exercise. MAIN OUTCOME MEASURES: Mean response time of VO2, mean oxygen deficit, and VO2 at anaerobic threshold (VO2-AT) and at peak exercise (VO2-peak) were determined. RESULTS: (1) LITE protocol: mean response time of VO2 = 35.1 (9.9) s; oxygen deficit = 418.3 (47.9) ml; oxygen deficit/VO2 time index = 54.7 (7.4). (2) RITE protocol: VO2-AT = 22.1 (5.7) ml/kg/min; heart rate at anaerobic threshold = 120.1 (3.6) beats/min; VO2-peak = 37.6 (10.7) ml/kg/min; peak heart rate = 167.8 (19.3) beats/min. The mean response time and oxygen deficit/VO2 time index were significantly correlated to VO2-peak and VO2-AT (P < 0.01). CONCLUSIONS: VO2 kinetics calculated in healthy controls may serve as a control database for assessing the rate response programming of pacemakers and its influence on VO2 during LITE. Because aerobic capacity below the anaerobic threshold is more likely to represent activity in daily life and the kinetics of VO2 are significantly related to VO2 at anaerobic threshold and peak exercise, LITE may provide a clinically useful correlate to peak exercise testing.
We investigated the physiologic heart rate (HR) to work rate (WR) relation throughout peak exercise in normal subjects as a guideline for rate-adaptive pacemaker slope programming. The study group consisted of 41 middle-aged subjects (22 men and 19 women) without evidence of cardiopulmonary disease. Peak-exercise stress tests were performed on a calibrated treadmill by using the symptom-limited "ramping incremental treadmill exercise" (RITE) protocol. The HR response, oxygen uptake, and treadmill workload increments were assessed simultaneously. The HR/WR slope, as determined using linear regression analysis, was 0.37 +/- 0.13 beats/min/W for the entire study group, which indicates an upper range increase of 5 beats/10 W increase of external treadmill work performed, using the mean value +/- 1 SD. Men generated an HR/WR slope of 0.32 +/- 0.09 beats/min/W, and women, 0.43 +/- 0.15 beats/min/W, indicating a significant sex-related difference in the HR/WR relation (p < 0.01). Thus, to achieve an appropriate matching of HR with patient effort, rate-adaptive pacemakers should generate an average increase of approximately 5 beats per increase in 10 W of external treadmill work. The HR/WR relation can easily be determined to provide the clinician with a minimal check system to avoid a hyper- or hypochronotropic paced response to exercise.
The objective of rate adaptive pacemakers that measure minute ventilation by transthoracic impedance is to simulate the physiological relationship of the sensed signal to the sinus node response during exercise, thus achieving an appropriate matching of heart rate with patient effort. The purpose of this study was to determine the physiological relationship between heart rate and minute ventilation (HR/VE) during peak exercise testing in order to develop a database for appropriate rate adaptive slope programming of minute ventilation controlled pacemakers. Due to several clinical limitations of peak exercise testing, it was additionally determined whether the 35-watt "low intensity treadmill exercise" (LITE) protocol can be used as a substitute for peak exercise test using the "ramping incremental treadmill exercise" (RITE) protocol in order to assess the correct HR/VE slope below the anaerobic threshold. The stress tests were performed on a treadmill with the collection of breath-by-breath gas exchange. Linear regression analysis was used to determine the HR/VE slope below and above the anaerobic threshold and during the early, dynamic phase of low intensity exercise with the RITE and LITE protocols, respectively. The results of this testing in 41 healthy subjects demonstrated that the HR/VE relationship throughout treadmill exercise using the RITE protocol was not linear but curvilinear in nature, with a steeper HR/VE slope of 1.54 +/- 0.51 below versus 1.15 +/- 0.37 above the anaerobic threshold (P < 0.005). The HR/VE slope determined during the early, dynamic phase of the LITE protocol (1.58 +/- 0.88) did not differ from the HR/VE slope from rest to anaerobic threshold obtained using the peak exercise RITE test (1.54 +/- 0.51; P = 0.79). Rate adaptive pacing should simulate the curvilinear relationship between heart rate and minute ventilation from rest to peak exercise. The HR/VE slope determined during the early, dynamic phase of low intensity exercise represents the HR/VE slope derived from the RITE protocol below the anaerobic threshold. According to the peak exercise database, the slope above anaerobic threshold can easily be calculated as a percentage of the slope below the anaerobic threshold. The LITE protocol can, therefore, be effectively performed as a substitute for peak exercise stress tests to determine the correct pacemaker rate response factor in order to obtain a physiological heart rate to minute ventilation relationship for the appropriate matching of paced heart rate with patient effort.