Michael Niehaus

High Incidence of Appropriate and Inappropriate ICD Therapies in Children and Adolescents with Implantable Cardioverter Defibrillator

Appropriate and inappropriate therapies of implantable cardioverter defibrillators have a major impact on morbidity and quality of life in ICD recipients, but have not been systematically studied in children and young adults during long‐term follow‐up. ICD implantation was performed in 20 patients at the mean age of 16 ± 6 years, 11 of which had prior surgical repair of a congenital heart defect, 9 patients had other cardiac diseases. Implant indications were aborted sudden cardiac death in six patients, recurrent ventricular tachycardia in 9 patient, and syncope in 5 patients. Epicardial implantation was performed in 6 and transvenous implantation in 14 patients. Incidence, reasons and predictors (age, gender, repaired congenital heart disease, history of supraventricular tachycardia, and epicardial electrode system) of appropriate and inappropriate ICD therapies were analyzed during a mean follow‐up period of 51 ± 31 months range 18‐132 months. There were a total 239 ICD therapies in 17 patients (85%) with a therapy rate of 2.8 per patient‐years of follow‐up. 127 (53%) ICD therapies in 15 (75%) patients were catagorized as appropriate and 112 (47%) therapies in 10 (50%) patients as inappropriate, with a rate of 1.5 appropriate and 1.3 inappropriate ICD therapies per patient‐years of follow‐up. Time to first appropriate therapy was 16 ± 18 months. Appropriate therapies were caused by ventricular fibrillation in 29 and ventricular tachycardia in 98 episodes. Termination was successful by antitachycardia pacing in 4 (3%) and by shock therapy in 123 episodes (97%). Time to first inappropriate therapy was 16 ± 17 months. Inappropriate therapies were caused by supraventricular tachycardia in 77 (69%), T wave oversensing in 19 (17%), and electrode defect in 16 episodes (14%). It caused shocks in 87 (78%) and only antitachycardia pacing in 25 episodes (22%). No clinical variable could be identified as predictor of either appropriate or inappropriate ICD therapies.

Atrial Reentrant Tachycardia After Surgery for Congenital Heart Disease Endocardial Mapping and Radiofrequency Catheter Ablation Using a Novel, Noncontact Mapping System

BackgroundThe purpose of the present study was to determine the role of a novel, noncontact mapping system for assessing a variety of atrial reentrant tachycardias (ART) in patients after the surgical correction of congenital heart disease. Methods and ResultsIn 14 patients, an electrophysiological study using the Ensite 3000 system was performed to assess ARTs resistant to medical treatment. Sixteen different forms of ART were inducible in the 14 patients studied. The reentrant circuit of all ARTs could be characterized and localized with respect to anatomic landmarks such as atriotomy scars, intraatrial patches/baffles, and cardiac structures. In 15 of the 16 ARTs (in 13 of the 14 patients), a target area of the reentrant circuit for radiofrequency current application (ie, an area of conduction between 2 anatomical obstacles such as surgical barriers and cardiac structures of electrical isolation) could be localized within the systemic venous atrium. Nine patients exhibited macroreentry, and 4 showed microreentry. In 12 patients, ART could be terminated by creating linear radiofrequency current lesions (75°C, 180 to 390 s). Completeness of linear lesions after radiofrequency current delivery was proven by analyzing color-coded isopotential maps of atrial activation while applying atrial pacing techniques. The mean duration of the procedures was 286 minutes (range, 130 to 435 minutes); fluoroscopy time ranged from 7 to 33.8 minutes (mean, 17.4 minutes). ConclusionsIn patients with ART after the surgical correction of congenital heart disease, the use of the noncontact mapping system allows for characterization of the tachycardia and guidance for effective radiofrequency current delivery.

Transplanted fetal cardiomyocytes as cardiac pacemaker

BACKGROUND While morphologic integration of transplanted fetal cardiomyocytes into the ventricular myocardium is a well-known fact, no studies have yet shown transplanted cells to coherently contribute to contraction and electrical excitation of the host myocardium. The aim of this study was to prove the hypothesis that by transplanting cardiomyocytes with a higher intrinsic rhythmic rate into the myocardium of the left ventricle, these cells could act as an ectopic pacemaker by functional coupling with host cardiomyocytes. METHODS AND RESULTS Dissociated fetal canine atrial cardiomyocytes including sinus nodal cells were delivered into the free wall of the left ventricle of adult canine X-linked muscular dystrophy dogs (n=2). These dogs fail to express Dystrophin in both cardiac and skeletal muscle. In the control group (n=2) fetal skin fibroblasts were used for grafting. A total of 3-4 weeks after transplantation the dogs underwent catheter ablation of the atrioventricular node (AV-node) and subsequent electrophysiological mapping studies. Transplanted cells were identified by Dystrophin immunoreactivity, indicating survival and morphological integration in the recipient heart. The expression of Connexin 43 between donor and recipient cells suggested formation of gap junctions between injected and host cardiomyocytes. After catheter ablation of the AV-node, a ventricular escape rhythm emerged driving the pace of the heart and originating from the labeled transplantation site. This effect could not be observed in the control group (n=2). CONCLUSIONS The results constitute the first observation of phenomena indicating electrical and mechanical coupling between allogeneic donor cardiomyocytes and recipient myocardium in-vivo. Further experiments are necessary to evaluate the technique as a potential therapy for atrioventricular block.

Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction

Objective: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. Methods: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. Results: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. Conclusions: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

Female Mice Lacking Estrogen Receptor β Display Prolonged Ventricular Repolarization and Reduced Ventricular Automaticity After Myocardial Infarction

Background—Major gender-based differences in the incidence of ventricular tachyarrhythmia after myocardial infarction have been shown in humans. Although the underlying mechanisms are unclear, earlier studies suggest that estrogen receptor–mediated effects play a major role in this process. Methods and Results—We examined the effect of estrogen receptor α (ERα) and estrogen receptor β (ERβ) on the electrophysiological phenotype in female mice with and without chronic anterior myocardial infarction. There was no significant difference in overall mortality, infarct size, and parameters of left ventricular remodeling when we compared infarcted ERα-deficient and ERβ-deficient mice with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks after myocardial infarction, surface ECG parameters did not show significant differences in comparisons of ERα-deficient mice versus wild-type controls, infarcted versus noninfarcted ERα-deficient mice, and infarcted ERα-deficient versus infarcted wild-type mice. However, infarcted ERβ-deficient versus noninfarcted ERβ-deficient mice showed a significant prolongation of the QT (61±6 versus 48±8 ms; P<0.05) and QTc intervals (61±7 versus 51±9 ms; P<0.05) and the JT (42±6 versus 31±4 ms; P<0.05) and JTc intervals (42±7 versus 33±4 ms; P<0.05). Furthermore, infarcted ERβ-deficient versus infarcted wild-type mice showed a significant prolongation of the QT (61±6 versus 53±8 ms; P<0.05) and QTc intervals (61±7 versus 53±7 ms; P<0.05) and the JT (42±6 versus 31±5 ms; P<0.05) and JTc intervals (42±7 versus 31±5 ms; P<0.05), accompanied by a significant decrease of ventricular premature beats (7±21/h versus 71±110/h; P<0.05). Finally, real-time polymerase chain reaction–based quantitative analysis of mRNA levels showed a significantly lower expression of Kv4.3 (coding for Ito) in ERβ-deficient mice (P<0.05). Conclusions—Estrogen receptor β deficiency results in prolonged ventricular repolarization and decreased ventricular automaticity in female mice with chronic myocardial infarction.

High prevalence of asymptomatic bacterial colonization of rhythm management devices

AIMS Recent work has been focused on causes of and risk factors for rhythm management device infections. The aim of this study was to elucidate whether patients may be asymptomatic carriers of bacteria on their rhythm management device, possibly allowing later manifestation of infection. METHODS AND RESULTS A total of 108 devices were changed for battery depletion between April 2005 and February 2006 in asymptomatic patients who were examined for evidence of bacterial DNA on the device and in the surrounding tissue using single strand conformation polymorphism analysis (SSCP). Follow-up was for 23.4 months. In 47.2% of the patients, bacterial DNA was demonstrated on the device, which had been in place for 64.1 months. The sequences identified bacterial strains that are untypical for clinical device infections. Staphylococci were demonstrated in only 3.7% of the patients and they became symptomatic within the observation interval; all others remained asymptomatic. The known risk factors for device infections did not correlate with the demonstration of bacterial DNA in this population. Common cohabitation was identified among the strains found. CONCLUSION A large proportion of patients carry bacteria on their pacemaker or implantable cardioverter defibrillator asymptomatically. The strains found differ from those commonly seen in clinically evident device infections. Common risk factors for device infection did not correlate with the presence of DNA.

Bimodal RR interval distribution in chronic atrial fibrillation: impact of dual atrioventricular nodal physiology on long-term rate control after catheter ablation of the posterior atrionodal input.

Bimodal RR Interval Distribution, Introduction: Radiofrequency (RF) catheter modification of the AV node hi patients with atrial fibrillation (AF) is limited by an unpredictable decrease of the ventricular rate and a wish incidence of permanent AV block, A bimodal RR histogram has been suggested to serve as a predictor for successful outcome but the corresponding AV node properties have never been characterized, We hypothesized that a bimodal histogram indicates dual AV nodal physiology and predicts a better outcome after AV node modification in chronic AF.

Comparison of a Novel, Single-Lead Atrial Sensing System With a Dual-Chamber Implantable Cardioverter-Defibrillator System in Patients Without Antibradycardia Pacing Indications: Results of a Randomized Study

Background—Supraventricular tachyarrhythmias are the main cause for inappropriate therapy by implantable cardioverter-defibrillators (ICDs). For better rhythm discrimination, an atrial electrogram is helpful and usually obtained from an additional atrial lead, even in the absence of sinus node or atrioventricular nodal disease. An A+-ICD system with integrated atrial sensing rings mounted 15 to 18 cm from the tip of an ICD lead may obviate the need to implant a separate atrial lead. The aim of the study was to compare the novel A+-ICD and a conventional dual-chamber (DR)-ICD. Methods and Results—Two hundred forty-nine patients with standard ICD indications but no requirement for antibradycardia pacing were randomized to receive an A+-ICD (n=124) or a DR-ICD (n=125). Implantation details, need for ICD system revision, long-term sensing, documented arrhythmia episodes, and the respective rhythm discrimination during follow-up were analyzed. The implantation time was significantly shorter in the A+-ICD group (67±30 vs 79±30 minutes, P=0.003). Mean P-wave amplitudes were 3.5±0.8 mV (A+-ICD) and 3.2±0.6 mV (DR-ICD) and remained stable during the follow-up period of 12 months. Surgical revision was necessary in 13 patients in the DR-ICD and 10 in the A+-ICD group. All 593 ventricular tachyarrhythmia episodes were correctly discriminated. Sensitivity and specificity of supraventricular tachyarrhythmia discrimination were not different between the study groups. Conclusions—The novel A+-ICD system can be implanted faster and is equivalent to a standard DR-ICD with regard to the detection of ventricular tachyarrhythmias and supraventricular tachyarrhythmias. It represents a useful alternative to obtain atrial sensing. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00324662.

Comparison of a Novel Single Lead Atrial Sensing (A+)-ICD System with a Dual Chamber ICD System in Patients without Antibradycardia Pacing Indications: Results of a Randomized Study

Background—Supraventricular tachyarrhythmias are the main cause for inappropriate therapy by implantable cardioverter-defibrillators (ICDs). For better rhythm discrimination, an atrial electrogram is helpful and usually obtained from an additional atrial lead, even in the absence of sinus node or atrioventricular nodal disease. An A+-ICD system with integrated atrial sensing rings mounted 15 to 18 cm from the tip of an ICD lead may obviate the need to implant a separate atrial lead. The aim of the study was to compare the novel A+-ICD and a conventional dual-chamber (DR)-ICD. Methods and Results—Two hundred forty-nine patients with standard ICD indications but no requirement for antibradycardia pacing were randomized to receive an A+-ICD (n=124) or a DR-ICD (n=125). Implantation details, need for ICD system revision, long-term sensing, documented arrhythmia episodes, and the respective rhythm discrimination during follow-up were analyzed. The implantation time was significantly shorter in the A+-ICD group (67±30 vs 79±30 minutes, P=0.003). Mean P-wave amplitudes were 3.5±0.8 mV (A+-ICD) and 3.2±0.6 mV (DR-ICD) and remained stable during the follow-up period of 12 months. Surgical revision was necessary in 13 patients in the DR-ICD and 10 in the A+-ICD group. All 593 ventricular tachyarrhythmia episodes were correctly discriminated. Sensitivity and specificity of supraventricular tachyarrhythmia discrimination were not different between the study groups. Conclusions—The novel A+-ICD system can be implanted faster and is equivalent to a standard DR-ICD with regard to the detection of ventricular tachyarrhythmias and supraventricular tachyarrhythmias. It represents a useful alternative to obtain atrial sensing. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00324662.

In-Vivo Electrophysiological Study in Mice with Chronic Anterior Myocardial Infarction

AbstractIntroduction: An increasing number of genetically altered mice with specific molecular cardiac defects are being assessed by electrophysiological studies and ECG monitoring. This approach should allow for the identification of critical genes involved in the arrhythmogenesis in myocardial infarction. Therefore it was the aim of this study to establish a standard for the in-vivo electrophysiological characteristics in the mouse model of chronic anterior myocardial infarction. Methods and Results: Using a minimized, invasive, in-vivo electrophysiological study, surface ECG parameters, sinus node function, atrial, atrio-ventricular and ventricular conduction and ventricular repolarization, and enhanced vulnerability to atrial and ventricular arrhythmia were studied in 20 wild-type C57BL/6 mice either under control or 11 weeks after large anterior myocardial infarction induced by ligation of the left anterior descending coronary artery. Telemetric ECG recording was performed in the same animals at baseline unrestrained, conscious condition to study surface ECG parameters, heart rate variability and the prevalence of supraventricular and ventricular arrhythmia. During electrophysiological study, infarcted mice showed an 81% increase of the angle of the QRS axis (p < 0.001) and a prolongation of the P wave by 23% (p = 0.01), the QRS complex by 39% (p = 0.001), the QT interval by 23% (p<0.05), the QTc interval by 30% (p < 0.005) and the JTc interval by 31% (p < 0.05) in comparison to control animals. Furthermore, there was a prolongation of the atrio-ventricular interval by 28% (p < 0.0005) and the atrio-ventricular functional refractory period by 26% in infarcted animals (p < 0.05), and inducibility of ventricular tachycardia in 4 of 6 infarcted versus in none of control animals (0 < 0.01). During telemetric ECG recording, there was a marked increase in ventricular ectopic activity in infarcted mice in comparison to controls (p < 0.05). Heart rate and time- and frequency-domain of heart rate variability were not significantly different in both groups (p > 0.05, respectively). Conclusions: The mouse model of chronic anterior myocardial infarction is associated with significant atrial and ventricular conduction disturbances and vulnerability to ventricular arrhythmia and thus may provide a highly valuable tool to study molecular determinants of arrhythmogenesis in myocardial infarction.