Transesophageal echocardiograpic imaging of de novo thrombus formation after successful external electrical cardioversion of atrial fibrillation.
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Biomedical subjects
Publications and source records attributed to W Jung.
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Adenosine provokes atrial fibrillation (AF) in some patients with paroxysmal supraventricular tachycardia (PSVT). Which patients are more susceptible to develop atrial fibrillation after the administration of adenosine to terminate PSVT is unknown. We prospectively measured atrial action potential duration (APD) at incremental doses of 3, 6, and 12 mg of adenosine at paced cycle lengths (CLs) of 600, 500, and 400 ms in 25 patients. Bolus injection of adenosine decreased APD at 90% repolarization in a dose- and rate-dependent manner. During paced CLs of 600, 500, and 400 ms, decreases of 8%, 13%, and 19% (p < 0.05), respectively, were found after bolus administration of 3 mg of adenosine. After 6 mg of adenosine, the APD shortened by 12%, 19%, (p < 0.05), and 27% (p < 0.01), respectively. After 12 mg of adenosine, the APD shortened by 15%, 27% (p < 0.05), and 38% (p < 0.01), respectively. Transient AF occurred in 4 of 25 (16%) patients, all during paced CLs of 400 ms, and after adenosine 6 mg in one patient and 12 mg in three patients. Adenosine shortens atrial action potential duration in a dose- and rate-dependent manner. Whether patients with faster rates during PSVT and those given higher doses of adenosine are more prone to develop atrial fibrillation remains to be determined.
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The case of a patient with recurrent VT and an ICD is reported. After appropriate device discharges, the patient experienced 40 episodes of inappropriate shock therapy due to atrial arrhythmias confirmed as type I atrial flutter. Since programmed stimulation could reliably initiate atrial flutter, catheter ablation was performed. During delivery of RF current, atrial flutter terminated and was no longer inducible. The patient had no further inappropriate device discharges during 12 months of follow-up. In patients with ICDs suffering from recurrences of atrial flutter leading to inappropriate shock therapy, RF catheter ablation is an effective and curative approach.
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.
OBJECTIVE: To determine whether echocardiographic markers thromboembolic risk differ between patients with pure atrial flutter and patients with atrial flutter and intermittent atrial fibrillation. DESIGN: Patients with atrial flutter were followed up prospectively for 12 months to identify intermittent atrial fibrillation. After the follow up period, transthoracic and multiplane transoesophageal echocardiography were performed to assess left atrial chamber and appendage size, peak emptying velocities, and emptying fraction of the left atrial appendage. The presence of spontaneous echo contrast was also determined. SETTING: Tertiary cardiac care centre. PATIENTS: 20 consecutive patients with atrial flutter; 11 healthy subjects in sinus rhythm served as controls. RESULTS: Intermittent atrial fibrillation was documented in 11 patients by Holter monitoring or surface ECG; atrial fibrillation was not found in the other nine patients. Compared with the patients with pure atrial flutter, patients with atrial flutter and intermittent atrial fibrillation had larger left atrial chamber (mean (SD) 4.5 (0.6) v 3.8 (0.5) cm; 95% confidence interval 0.2 to 1.2; P = 0.01) and appendage areas (6.7 (2.2) v 4.8 (4.9) cm; 95% CI 0.4 to 3.5; P = 0.02), lower left atrial appendage emptying fractions (33 (11)% v 52 (11)%; 95% CI 8 to 29; P = 0.008), and also lower left atrial appendage emptying velocities (0.44 (0.21) v 0.79 (0.27) m/s; 95% CI 0.13 to 0.56; P = 0.005). In addition, a higher incidence of spontaneous echo contrast (11% v 36%) was observed in patients with atrial flutter and intermittent atrial fibrillation. CONCLUSIONS: Left atrial appendage function is depressed and spontaneous echo contrast more frequent in patients with atrial flutter and intermittent atrial fibrillation, as opposed to patients with pure atrial flutter. These data support the concept that patients with atrial flutter and intermittent atrial fibrillation have an increased risk of thromboembolic events and should therefore receive adequate anticoagulant treatment.
UNLABELLED: The efficacy of a treatment is primarily based on objective criteria, such as mortality and morbidity. Besides these criteria, the interest in measuring quality of life (QOL) in relation to health care has increased in recent years. Although the concept of patients' QOL is inherently subjective, and definitions vary, it can be assessed on a basis of 3 major components: physical condition, psychological well-being, and social activities. The basic requirements of QOL assessments are: multidimensional construct, reliability, validity, sensitivity, responsiveness, appropriateness to question or use, and practical utility. The instruments to assess QOL can be disease specific or generic, depending on the context. In 1991 a prospective and systematic evaluation of QOL in implantable cardioverter-defibrillator (ICD) recipients was started at the University of Bonn: psychological profile and patient acceptance were assessed in 57 consecutive patients using a specifically designed questionnaire. The results of this pilot study demonstrated that the acceptance of the ICD was remarkably high. Restrictions on driving a vehicle may have a substantial impact on QOL in patients with ICDs. A specifically designed questionnaire was addressed to 47 European national delegates in order to determine their present practices and criteria utilized when advising driving restrictions to patients after ICD implantation. Of the 39 (83%) respondents, 22 (56%) cardiologists advised all patients to abstain from driving--13 (33%) advising permanent abstinence, while 26 (67%) recommended temporary driving abstinence for periods of 3-18 months (mean 9 +/- 4 months). Despite medical advice not to drive, one third of the patients resume driving; half of the patients resumed driving after 6 months, with the vast majority driving within 12 months after ICD surgery. Two patients experienced ICD discharges while driving, but no motor vehicle accident occurred. Another patient had a motor vehicle collision with a fatal outcome, which was not caused by loss of consciousness or ICD discharge. CONCLUSIONS: (1) Fatal accidents or ICD discharges while driving are a rare finding in ICD patients. (2) About half of the physicians always advise their patients to cease driving for a period of 9 +/- 4 months. Despite this medical advice, the majority of the patients resume driving within 6 months of ICD implantation. (3) Criteria used in advising driving abstinence are not uniform among physicians.
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To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross-linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI-MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T-cell deficiency in patients with Hodgkin's disease.
Cure of a single established human Hodgkin's tumor growing subcutaneously in severe combined immunodeficient (SCID) mice can be achieved with a complex protocol using two bispecific monoclonal antibodies (Bi-MoAb) directed against the Hodgkin's associated CD30 antigen and the T-cell triggering molecules CD3 and CD28, respectively, together with human T cells prestimulated in vitro with Bi-MoAbs in the presence of CD30+ cells. To adapt this model to the clinical situation, disseminated tumors were established in SCID mice by intravenous injection of 2 x 10(7) cells of the Hodgkin's derived cell line L540CY. Treatment of SCID mice bearing disseminated CD30+ Hodgkin's tumors with the combination of CD3/CD30 and CD28/CD30 Bi-MoAbs and naive (ie, not in vitro prestimulated) human T cells resulted in the cure of all appropriately treated animals. T lymphocytes obtained from patients with advanced stage untreated Hodgkin's disease were as effective as lymphocytes from healthy controls. Treatment was effective even when delayed until 2 weeks after tumor inoculation, and application of Bi-MoAbs into SCID mice with circulating human T cells was as effective as injecting the Bi-MoAbs before the lymphocytes. Treatment results with isolated CD4+ and CD8+ human T cells suggest that both subsets are necessary for the Bi-MoAb mediated cure of xenografted human tumors in vivo. The efficacy and practicability of this preclinical immunotherapy protocol support and form the basis for the clinical evaluation of this approach in patients with Hodgkin's disease resistant to standard therapy.
AIM OF STUDY: To investigate how medical permission to drive in patients with a cardioverter defibrillator is handled in various European countries. METHODS: A specially developed questionnaire was sent to all 46 delegates of the pacemaker groups of the European Society of Cardiology. They were asked to provide information on the procedures and criteria used in the various countries regarding a driving ban after cardioverter defibrillator implantation (ICD). RESULTS: 39 answers (83%) were received from representatives of 24 countries. 22 (56%) of those replying advised their patients not to drive. A permanent driving ban was recommended by 13 (33%), a temporary one of 3-18 (mean 9 +/- 4) months by 26 (67%). Presyncope was named as a criterion for a ban by 15 (38%), syncope by 13 (33%) and multiple defibrillator shocks by two (5%). Contrary to medical advice not to drive about one third of patients resumed driving, half of them after 6 months. 12 months after implantation most of the patients were again driving. Defibrillator discharges occurred in 2 patients, without consequence. One patient had a fatal car accident, unrelated to loss of consciousness or defibrillator shock. CONCLUSIONS: 1. ICD discharges are an extremely rare cause of driving accidents. 2. About half of the cardiologists recommended a driving ban for a mean of 9 months after ICD. 3. Despite medical ban about half of the patients resumed driving after 6 months. 4. There are as yet no uniform criteria in Europe for judging fitness to drive.
Nonpharmacologic tools to treat atrial fibrillation (AF) are direct current cardioversion, radiofrequency (RF) current catheter ablation, antiarrhythmic surgery, pacing, and atrial defibrillation. In patients with sustained AF, when no cause can be found for AF or when the associated disease is mild, an attempt should be made to restore sinus rhythm. Electrical cardioversion by synchronized direct current shock can be attempted when drugs have failed and is the first choice in acutely ill patients. Virtually all patients should be anticoagulated. Temporary pacing should be available in patients with evidence of previous bradycardia. Although efficacy may be improved in patients pretreated with antiarrhythmic drugs, there is a considerable risk of adverse events. In AF and sinus node dysfunction, both pacing and antiarrhythmic drugs may be necessary. Pacing should be atrial or dual chamber, since ventricular pacing provokes AF. Failure to control the ventricular rate in AF can be treated by RF: atrioventricular (AV) node ablation, ablation of accessory pathways in preexcitation syndrome with AF, modulation of AV node, or ablation of AF. Antiarrhythmic surgery is a major procedure and may be the therapy of last resort in AF: the so-called corridor procedure isolates the fibrillating atria from a strip of tissue connecting the sinus and AV nodes. The maze procedure attempts to abolish AF by channeling the atrial activation between a series of incisions. In patients with chronic AF, internal cardioversion should be attempted if conventional transthoracic electrical cardioversion is ineffective. Several studies demonstrated the feasibility and efficacy of internal atrial defibrillation in selected patients with recent onset, as well as with chronic, AF. An implantable atrial defibrillator--as a stand-alone device or as part of a whole heart cardioverter--might be an option in the future. Nonpharmacologic tools play only a minor role in the management of paroxysmal and chronic AF. If symptoms persist despite pharmacologic therapy and other causes of persisting symptoms are excluded, consideration should be given to cardiac pacing, RF catheter treatment, or surgery. in some cases nonpharmacologic therapy of the AV node must be followed by implantation of a permanent pacemaker (due to complete AV block) and anticoagulation (due to persistence of underlying AF.
We investigated whether captopril is able to potentiate vasodilation and prevent tolerance to a 48-hour infusion of nitroglycerin (NTG). Twenty-six patients were randomly assigned to a 7-day regimen of captopril (50 mg/day) or placebo. The hemodynamic response to a 0.8 mg sublingual NTG dose was assessed by measuring mean arterial pressure (MAP), mean pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), and cardiac output (CO), and calculating systemic (SVR) and pulmonary vascular resistances (PVR). The parameters were obtained serially at baseline and 1 to 10 minutes after the sublingual NTG application (day 1). Then intravenous NTG was started and maintained for 48 hours (1.5 micrograms/kg/min), and the hemodynamic study was repeated (day 3). There was no difference between the captopril and the placebo groups at day 1 (baseline values and response to sublingual NTG). After the 48-hour infusion, there was a complete loss of the NTG effects in the placebo group (day 1 vs day 3: PAP, 20 +/- 5 mm Hg vs 21 +/- 8 mm Hg; MAP, 86 +/- 11 mm Hg vs 90 +/- 9 mm Hg; SVR, 1295 +/- 330 mm Hg vs 1380 +/- 465 dyne.sec.cm-5) whereas there was still evidence of a persistent vasodilation in the captopril group (day 1 vs day 3: PAP, 19 +/- 4 mm Hg vs 13 +/- 4 mm Hg; MAP, 84 +/- 9 mm Hg vs 74 +/- 10 mm Hg; SVR, 1265 +/- 280 mm Hg vs 1140 +/- 425 dyne.sec.cm-5). The response to sublingual NTG on day 3 was markedly attenuated in the placebo group only. We conclude that captopril does not increase the vasodilatory response to nitroglycerin but is able to prevent developing nitrate tolerance in arterial and venous circulation.
Bispecific monoclonal antibodies (Bi-MAbs) with dual specificity for tumor-associated antigens (TAA) and a triggering molecule of an immunologic effector cell, respectively, open the possibility to specifically target to and activate cytotoxic effector cells (macrophages, T-cells, NK cells) at the tumor site. Using appropriately designed Bi-MAbs and unstimulated human NK cells and T-cells, respectively, we were able to cure SCID mice xenografted with human Hodgkin's tumors. This approach was also effective in disseminated tumors and when treatment was delayed until three weeks after the inoculation of the tumor, thus establishing this approach as the most effective model of an immunomodulating therapy of human neoplasms. Early observations with an ongoing phase I/II study with CD16/CD30 Bi-MAb in patients with refractory Hodgkin's disease confirm the expected low toxicity. If these observations can be confirmed in larger clinical studies, effector cell activating Bi-MAbs could become an important weapon in the remaining fight for the conquest of Hodgkin's disease.
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The purpose of this study was to determine the incidence and types of venous branches and anomalies in posteroseptal accessory pathways (APs) and whether these findings are indicative for successful ablation sites. Some posteroseptal APs may be located epicardially, or may be associated with venous anomalies or related to the middle cardiac vein. These APs account for many of the failures encountered during endocardial ablation. Direct coronary sinus (CS) angiography was performed in 43 consecutive patients with left posteroseptal APs (n = 23) and in 20 patients with AV nodal reentrant tachycardia prior to catheter ablation. In 14 (61%) of 23 APs, a venous branch or an anomaly of the CS was found in the posteroseptal region (6 with middle cardiac vein, 2 with other ventricular venous branches, and 6 had a diverticulum). Eleven (48%) of 23 APs were successfully abolished from within that demonstrated venous system, with a median of four radiofrequency impulses. In the remaining 12 (52%) patients, ablation was attempted from the endocardial site of the mitral annulus. Repeat angiography after energy delivery revealed no major complications in any patient. One (5%) patient with AV nodal reentrant tachycardia had evidence of a CS anomaly (P < 0.01). Various types of venous branches and anomalies are associated with the majority of patients with left posteroseptal APs. The APs are directly related to these complex findings, and AP conduction can easily be eliminated from within the venous branches. CS angiography is suggested prior to catheter ablation of left posteroseptal APs to facilitate the ablation procedure.
UNLABELLED: The pectoral approach to implantation of cardioverter/defibrillators has the aim to further simplify the implantation of transvenous defibrillation systems. The PCD 7219 D/C is a device of the fourth generation which makes the pectoral implantation feasible due to a weight of 132 g, a size of 89 x 64 x 18 mm, a volume of 83 cm3 and a surface of 108 cm2. The use of the "active-can"-system (PCD 7219 C) requires the implantation of only one right ventricular lead. The PCD 7219 D/C was implanted in 75 patients with ventricular tachyarrhythmias, the follow-up period was 12 +/- 4 (1-24) months. Subpectoral implantation was feasible in 59 patients (79%), in 55 with a left pectoral, in 4 with a right pectoral approach due to previous left-sided operation or thrombosis of the left subclavian vein. Male sex (p < 0.005), body weight (p < 0.005) and body surface (p < 0.05) were predictors of pectoral implantation. In the 45 patients (60%) with a unipolar defibrillation system ("active can") the defibrillation threshold was significantly lower compared to those with a dual lead system (9.9 +/- 6.5, 2.5-24 Joule vs. 19 +/- 4.5, 6-24 Joule p < 0.0001). In one patient with pectoral and in one patient with abdominal implantation a dislodgement of the right ventricular lead was diagnosed and an operative revision was indicated. CONCLUSION: The down-sized implantable cardioverter/defibrillator PCD 7219 D/C makes the pectoral implantation feasible in the majority of patients. The use of the "active-can"-system requires the implantation of only one right ventricular lead with significantly lower defibrillation thresholds.