Sex hormones and arrhythmia in myocardial ischemia.

The mechanisms by which gender affects cardiac electrophysiological parameters and alters the predisposition to certain arrhythmias are not well understood, although differences in the expression and function of ion channels and in the activation of the autonomic nervous system may contribute. In their study Philp and coworkers address the issue of the effect of 17beta-estradiol on ventricular vulnerability in a rat model of ischemia. Their data show that there is a dose-dependent antiarrhythmic activity of 17beta-estradiol administration with suppression ventricular premature beats, ventricular tachycardia and ventricular fibrillation during ischemia. Furthermore they show a dose-dependent blockage of I(CaL) by 17beta-estradiol which is again stronger in female than in male mice. They postulate that the shown gender-selective, concentration-dependent inhibition of I(CaL) is sufficient to account for the reduction in ischaemia-induced arrhythmia. With this data they have added important information on the influence of sex hormones on cardiac electrophysiology under pathophysiological conditions.

IEGM-online based evaluation of implantable cardioverter defibrillator therapy appropriateness.

Appropriate and inappropriate therapies of implantable cardioverter defibrillators have a major impact on morbidity and quality of life in ICD recipients. Intracardiac electrograms (IEGMs) stored in the ICD have been shown to be essential for differentiating appropriate and inappropriate ICD therapies. The recently introduced third generation of ICD Home Monitoring offers remotely transmitted IEGMs (IEGM-online). Hence, the appropriateness of ICD therapies might be remotely assessed. Validation of these electrograms is currently being performed in the RIONI study. A total of 210 episodes will be collected by about 40 European clinical centers. The study primarily investigates whether the IEGM-online based evaluation of the appropriateness of the ICD's therapeutic decision following a tachyarrhythmia episode detection is equivalent to the evaluation based on the complete ICD episode holter. The evaluation is independently performed by an expert board of three experienced ICD investigators. The equivalence of the two methods is accepted if the conclusions deviate for less than 10% of all evaluated IEGMs. Secondary endpoints investigate the IEGM-online usefulness in more detail. The conclusion of the study is expected by mid of 2007. RIONI has successfully been started for proving the reliability of IEGM-online. The expected results will significantly influence the efficacy of Home Monitoring based patient management.

The RIONI study rationale and design: validation of the first stored electrograms transmitted via home monitoring in patients with implantable defibrillators.

Appropriate and inappropriate therapies of implantable cardioverter defibrillators (ICDs) have a major impact on morbidity and quality of life in ICD recipients. The recently introduced home monitoring of ICD devices is a promising new technique which remotely offers information about the status of the system. Stored intracardiac electrograms (IEGMs), which are essential for correct classification of appropriate and inappropriate ICD discharges, have until now not been available with ICD home monitoring on a day-by-day basis because of limitations of transferable data. We demonstrate the first compressed IEGMs daily transferable via home monitoring (IEGM-online). Validation of these electrograms will be performed in the Reliability of IEGM-Online Interpretation (RIONI) study. A total of 210 episodes of stored IEGMs will be collected by at least 12 European centres. The primary endpoint of this study is to investigate whether the IEGM-online based evaluation of the appropriateness of the ICDs therapeutic decision following episode detection is equivalent to the evaluation based on the complete ICD episode Holter extracted from the IEGM stored. The evaluation is independently done by an expert board of three experienced ICD investigators. The equivalence of the two methods is accepted if the evaluations yield a different conclusion for <10% of all evaluated IEGMs. The conclusion of the study is expected at the beginning of 2007. If RIONI successfully validates IEGMs transmitted via home monitoring, a strong basis for the use of this promising technique will be established.

[Therapy of atrial fibrillation]. / Therapie des Vorhofflimmerns.

Atrial fibrillation is the most common cardiac arrhythmia in adults. Paroxysmal atrial fibrillation terminates spontaneously, whereas the persistent form terminates only after medical or electrical cardioversion. Permanent atrial fibrillation cannot be cardioverted. Restoration of sinus rhythm can be achieved by antiarrhythmic drugs or electrical cardioversion, both performed under continuous electrocardiographic monitoring. If atrial fibrillation has lasted longer than 48 hours or the precise time of onset cannot be determined, there are two alternative approaches: systemic anticoagulation to achieve an international normalised ratio (INR) of 2.0 to 3.0 for at least three weeks, followed by cardioversion; or cardioversion guided by transesophageal echocadiography indicating the absence of thrombus. Several drugs have been shown to be effective for the maintenance of sinus rhythm. Anticoagulant therapy is mandatory for a minimum of three weeks after cardioversion. In case of drug refractory, highly symptomatic atrial fibrillation the indication for radiofrequency catheter ablation should be discussed, although the value of this new method is still under evaluation.

[Arrhythmogenic right ventricular dysplasia/cardiomyopathy - diagnosis in childhood]. / Arrhythmogene rechtsventrikuläre Dysplasie/Cardiomyopathie. Diagnostik im Kindesalter.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare, but important cause for sudden death in adolescents and young adults. Part of the patients affected show the pattern of autosomal-dominant inheritance. Two pediatric patients with ARVD/C are presented who may reflect the spectrum of clinical presentation of ARVD/C in childhood resulting in difficulties or even delay to establish the correct diagnosis. One patient with a sporadic form of ARVD/C presented with a syncope and spontaneous as well as inducible ventricular tachycardia. On the ECG, an epsilon wave could be identified. An automatic cardioverter defibrillator was implanted. The second patient had a familiar form of ARVD/C with no symptoms. There was a history of frequent sudden deaths in this family. Biopsies of the right ventricular myocardium showed fibrosis with deposition of fatty tissue. There was clear evidence of ARVD/C in the necropsy of the patient's aunt. Therapy with propanolol was started in this patient.

Different Yersinia enterocolitica 4:O3 genotypes found in pig tonsils in Southern Germany and Finland.

The distribution of different genotypes of Y. enterocolitica 4:O3 strains recovered from pig tonsils in Southern Germany and Finland in 1999-2000 was investigated. A total of 96 and 207 Y. enterococolitica 4:O3 isolates recovered from 47 and 66 tonsils of finishing pigs in Germany and Finland, respectively, were characterised with PFGE using NotI enzyme. In all, 39 different NotI profiles were obtained, only one of which, NB1, was found in both Germany and Finland. All strains were further characterised with ApaI and XhoI enzymes. When the 54 German and 74 Finnish strains were characterised with all three enzymes, 51 genotypes were obtained. The 23 genotypes found in German strains differed from the 28 found in Finnish strains. These results indicate that Y. enterocolitica 4:O3 genotypes have a differential geographical distribution and thus can be used in epidemiological studies.

Efficacy of antitachycardia pacing confirmed by stored electrograms. A retrospective analysis of 613 stored electrograms in implantable defibrillators.

The implantable defibrillator (ICD) is an established therapy in the prevention of sudden cardiac death by defibrillation of ventricular fibrillation. Another specific feature of the ICDs is antitachycardia pacing (ATP) of ventricular tachycardia. Several studies report success rates of ATP in 83 to 98% of cases. In clinical practice the success of terminating ventricular tachycardia is estimated only by automatic device analysis. Therefore the objective of this study was to confirm the efficacy of ATP based on the evaluation of stored electrograms. From the German Ventritex MD-register stored electrograms of 613 monomorphic ventricular tachycardias in 44 patients were analyzed retrospectively. The cycle length of the ventricular tachycardias was between 265 and 560 ms. The success rate of ATP-induced termination of the episodes reached 89.3%; another 2.3% of the ventricular tachycardias were accelerated by antitachycardia pacing into ventricular fibrillation. Left ventricular function did not influence the success rate, but the success rate was lower for fast ventricular tachycardias > 200/min (63.9%). For ventricular tachycardias < 150 bpm there was no restriction of ATP effectiveness. Of the episodes 72.9% were terminated by the first ATP burst. In these cases the duration of tachycardia was very short (11.9 +/- 2.8 s). Fifty-eight ventricular tachycardias (9.5%) had to be terminated by means of a shock, and only one case required 2 shocks. In patients with more than 10 episodes an individual therapy success > 90% was recorded for 80% of them. The very high success rate of the first ATP attempt in ICD therapy can be achieved with uniform programming, and is confirmed for ventricular tachycardias analyzed on the basis of stored electrograms.

Multicenter experiences with a single lead electrode for dual chamber ICD systems.

Monitoring of atrial signals improves the accuracy in identifying supraventricular tachyarrhythmias to prevent inappropriate therapies in patients with implantable ICDs. Since difficulties due to the additional atrial lead were found in dual chamber ICD systems with two leads, the authors designed a single pass VDD lead for use with dual chamber ICDs. After a successful animal study, the prototype VDD lead (single coil defibrillation lead with two additional fractally coated rings for bipolar sensing in the atrium) was temporarily used in 30 patients during a German multicenter study. Atrial and ventricular signals were recorded during sinus rhythm (SR), atrial flutter, AF, and VT or VF. The implantation of the lead was successful in 27 of 30 patients. Mean atrial pacing threshold was 2.5 +/- 0.9 V/0.5 ms, mean atrial impedance was 213 +/- 31 ohms. Atrial amplitudes were greater during SR (2.7 +/- 1.6 mV) than during atrial flutter (1.46 +/- 0.3 mV, P < 0.05) or AF (0.93 +/- 0.37 mV, P < 0.01). During VF atrial "sinus" signals had significantly (P < 0.01) lower amplitudes (1.4 +/- 0.52 mV) than during SR. The mean ventricular sensing was 13.3 +/- 7.9 mV and mean ventricular impedance was 577 +/- 64 ohms. Defibrillation was successful with a 20-J shock in all patients. In addition, 99.6% of P waves could be detected in SR and 84.4% of flutter waves during atrial flutter. During AF, 56.6% of atrial signals could be detected without modification of the signal amplifier. In conclusion, a new designed VDD dual chamber lead provides stable detection of atrial and ventricular signals during SR and atrial flutter. Reliable detection of atrial signals is possible without modification of the ICD amplifier.

Morphology discrimination: a beat-to-beat algorithm for the discrimination of ventricular from supraventricular tachycardia by implantable cardioverter defibrillators.

Inappropriate therapy of SVTs by ICDs remains a major clinical problem despite enhanced detection criteria like "sudden onset" and "rate stability" in third-generation devices. Electrogram morphology discrimination offers an additional approach to improve discrimination of supraventricular tachycardia (SVT) from ventricular tachycardia (VT). In a prospective, multicenter study, patients received an ICD with a beat-to-beat algorithm for morphological analysis of the intracardiac electrogram (Morphology Discrimination, MD). A nominal programmingfor standard enhancement criteria and morphology discrimination was required at implant. Electrogram storage of tachycardia episodes irrespective of delivery of therapy was used to assess sensitivity and specificity of the morphology algorithm alone and in combination with established detection criteria. During a 126 6-month follow-up, 886 episodes of device stored electrograms from 82 of 256patients were evaluated. Atnominal settings, the MD algorithm correctly identified 423 of 551 episodes as VT resulting in sensitivity of 77%. The classification of SVT was met in 239 of 335 episodes resulting in specificity of 71%. In combination with sudden onset, sensitivityincreased to 99.5% at the expense of specificity (48%). In conclusion, SVT-VT discrimination based on morphological analysis alone results in limited sensitivity and specificity. Programming the monitor mode allows individual assessment of the performance of this detection enhancement feature during clinical follow-up without compromising device safety. Only in patients with documented efficacy of morphology discrimination should this feature be subsequently activated.

Role of the Glu residues of the influenza hemagglutinin fusion peptide in the pH dependence of fusion activity.

To elucidate the role of the fusion peptide in influenza hemagglutinin (HA)-mediated fusion, we compared pH-dependent conformational changes and fusion mediated by wild-type and a mutant HA in which Glu residues at positions 11 and 15 of the fusion peptide are substituted for valine. The pH dependence of conformational changes and kinetics of fusion with erythrocytes was the same for both forms of HA. The time for commitment and the temperature dependence of HA-mediated fusion were also the same. However, striking differences were observed between wild-type and mutant fusion peptides in their interactions with lipid membranes at neutral and acidic pH. Since elimination of the negatively charged residues allows the exposed fusion peptide to penetrate the bilayer at pH values closer to neutral, but does not affect conformational changes and fusion activity in intact HA, we conclude that conformational changes are tightly coupled to fusion peptide insertion in the overall HA-mediated fusion cascade.

Correspondence of genotypes of sporadic Yersinia enterocolitica bioserotype 4/O:3 strains from human and porcine sources.

The sources and transmission routes of sporadic Yersinia enterocolitica bioserotype 4/O:3 infections in Finland were studied. A total of 212 human strains were compared with 334 non-human strains, including 163 strains from pig slaughterhouses, 164 strains from retail outlets and 7 strains from pet animals. All strains were characterized using pulsed-field gel electrophoresis (PFGE) with NotI enzyme. When the 194 human and 287 non-human strains of 22 identical NotI profiles were further characterized with ApaI and XhoI enzymes, 126 genotypes (DI = 094) were distinguished. Of all 212 human strains, 80% were genetically indistinguishable from the strains found in samples of pig origin when characterized with the three enzymes. A major contamination source of sporadic Y. enterocolitica 4/O:3 infections was revealed to be edible pig offal: 71% of the human strains were indistinguishable from the strains isolated from tongues, livers, kidneys and hearts of pigs. These results reveal that in Finland contaminated pig offal is an important vehiclein the transmission of Y. enterocolitica bioserotype 4/O:3 from slaughterhouses to humans.

Prospective evaluation of catheter ablation in patients with implantable cardioverter defibrillators and multiple inappropriate ICD therapies due to atrial fibrillation and type I atrial flutter.

The high incidence of inappropriate therapies due to drug refractory supraventricular tachycardia remains a major unsolved problem of the ICD. Most of the inappropriate therapies for supraventricular tachycardia are caused by AF and type I atrial flutter with rapid ventricular response. The purpose of this prospective study was to determine the usefulness of AVN modulation or ablation for rapid AF and ablation of the tricuspid annulus-inferior vena cava (TA-IVC) isthmus for type I atrial flutter in ICD patients with frequent inappropriate ICD interventions. Eighteen consecutive patients were enrolled in this study. Twelve patients received a mean of 34 +/- 36 antitachycardia pacing (ATP) and 41 +/- 32 shock therapies for rapid AF during 49 +/- 39 months, and 6 patients a mean of 111 +/- 200 ATP and 11 +/- 8 shock therapies for type I atrial flutter during 52 +/- 37 months preceding ablation procedure. Modification of the AVN was successful in 10 (83%) of 12 AF patients, in 2 (17%) patients ablation of the AVN was performed. A complete TA-IVC isthmus block was achieved in 5 (83%) of 6 atrial flutter patients. Three (25%) AF patients had 11 +/- 24 recurrences of ATP and 0.4 +/- 1.1 shock therapies for rapid AF during 15 +/- 7 months. None of the atrial flutter patients had recurrences of inappropriate therapies for type I atrial flutter during 14 +/- 8 months, but two (33%) patients had inappropriate ICD therapies for type II atrial flutter or rapid AF. There was an overall mean incidence of 18 +/- 22 inappropriate ICD therapies per 6 months before and 4 +/- 9 per 6 months after the ablation procedure (P < 0.05). In conclusion, radiofrequency catheter modification or ablation of the AVN for rapid AF and ablation for atrial flutter type I are demonstrated to be highly effective in the majority of ICD patients with drug refractory multiple inappropriate ICD therapies.

Transmission of Yersinia enterocolitica 4/O:3 to pets via contaminated pork.

AIMS: This study was conducted to investigate sources of Yersinia enterocolitica 4/O:3 infections in dogs and cats. METHODS AND RESULTS: Transmission of Y. enterocolitica 4/O:3 to pets via contaminated pork was studied using PFGE with NotI, ApaI and XhoI enzymes. A total of 132 isolates, of which 16 were from cat and dog faeces and 116 from raw pork samples, were recovered in Finland during 1998-99. Cat 1, whose diet consisted mostly of raw pig hearts and kidneys, excreted Y. enterocolitica 4/O:3 of genotype G4. This predominant genotype was also found in isolates recovered from the pig heart, liver, kidney, tongue and ear, and minced pork samples. Dog 2, which was fed raw minced pork, excreted Y. enterocolitica of genotype G13. This genotype was also identified in isolates recovered from the pig heart, kidney and tongue, and minced pork samples. CONCLUSION: These results show that raw pork can be an important source of Yersinia enterocolitica 4/O:3 infections in dogs and cats. SIGNIFICANCE AND IMPACT OF THE STUDY: Raw pork should not be given to pets.

Atrial reentrant tachycardia after surgery for congenital heart disease: endocardial mapping and radiofrequency catheter ablation using a novel, noncontact mapping system.

BACKGROUND: The 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 RESULTS: In 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 degrees 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). CONCLUSIONS: In 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.

[Usefulness of a VDD defibrillation electrode in recording atrial electrograms during atrial flutter and atrial fibrillation]. / Nutzen einer VDD-Defibrillationselektrode zur Aufzeichnung von atrialen Elektrogrammen bei Vorhofflimmern/-flattern.

BACKGROUND: Monitoring of atrial signals improves the accuracy in identifying supraventricular tachyarrhythmias to prevent inappropriate therapies in patients with implantable cardioverter-defibrillators (ICD). Since complications due to the additional atrial lead were found in dual chamber ICD systems with 2 leads, we designed a single-pass VDD-lead for use with dual chamber ICDs. PATIENTS AND METHODS: After promising animal experiments in a German multicenter study a prototype VDD lead (single-coil defibrillation electrode with 2 additional fractally coated rings for bipolar sensing in the atrium) was temporarily used in 20 patients. Atrial and ventricular signals were recorded during sinus rhythm, atrial flutter, atrial fibrillation and ventricular tachycardia or ventricular fibrillation. Terminations of ventricular arrhythmias were performed by internal DC shock. RESULTS: The implantation of the electrode was successful in 18 of 20 patients. Mean atrial pacing threshold was 2.45 +/- 0.9 V/0.5 ms, mean atrial impedance was 215 +/- 31 Ohm. Atrial amplitudes were greater during sinus rhythm (2.7 +/- 1.6 mV) than during atrial flutter (1.36 +/- 0.28 mV, p < 0.05) or atrial fibrillation (0.92 +/- 0.29 mV, p < 0.01). During ventricular fibrillation atrial "sinus"-signals had significantly (p < 0.01) lower amplitudes than during sinus rhythm. Mean ventricular sensing was 13.3 +/- 7.9 mV, mean ventricular impedance was 577 +/- 64 Ohm. Defibrillation was successful with 20 J shock. 99.6% of P waves could be detected in sinus rhythm and 85 +/- 9.9% of flutter waves during atrial flutter. During atrial fibrillation 55% of atrial signals could be detected without modification of the signal amplifier. CONCLUSIONS: A new designed VDD dual chamber electrode provides stable detection of atrial and ventricular signals during sinus rhythm and atrial flutter. For reliable detection of atrial fibrillation modifications of the signal amplifier are necessary.

[Implantable cardioverter/defibrillator: long-term stability of the defibrillation threshold with a unipolar electrode configuration (active-can")]. / Implantierbarer Kardioverter-/Defibrillator: Langzeitstabilität der Defibrillationsschwelle mit einer unipolaren Elektrodenkonfiguration ("Active-Can").

The majority of cardioverter/defibrillator (ICD) implantations are currently performed with a non-thoracotomy approach. From November 1993 to January 1995, 46 patients underwent implantation of a PCD 7219C with an "active-can" lead configuration at our institution. While the chronic stability of the defibrillation threshold (DFT) for an epicardial lead system is well established, the results are still inconsistent for non-thoracotomy lead systems. Accordingly, the aim of the present study was to compare the acute and chronic defibrillation thresholds of the ICDs implanted with an "active-can" lead system in order to assess the chronic stability of these systems. The defibrillation energy requirements were measured at implant, prior to hospital discharge, three, six and twelve months after implantation of the defibrillator. The patient group consisted of 8 females and 38 males with a mean age of 57.2 years. The mean left ventricular ejection fraction was 43.8%. The most frequent underlying heart disease was coronary artery disease in 31 of 46 patients. Eight patients had idiopathic dilated cardiomyopathy. In 39 of 46 patients, the defibrillation threshold could be successfully determined at all 4 time points after implantation. The mean defibrillation energy requirement at the time of implantation was 9.2 +/- 5.9 Joules (J). The subsequent mean energy requirements were 7.6 +/- 4.8 J at pre-hospital discharge, 8.6 +/- 5.7 J at the 3 month, 8.1 +/- 6.0 J at the 6 month and 8.6 +/- 5.8 J at the 12 month follow-up visits. The mean defibrillation threshold was lowest at the time of prehospital discharge, significantly lower than at the time of initial implantation (p = 0.021). However, at all later time points up to one year, there was no significant difference in the DFT as compared with the time of initial implantation. Comparing the DFT at the time of implantation and the DFT at all other time points, there were no significant differences (9.23 vs. 8.56 J, p = 0.291). Although there was an initial decrease in the DFT at seven to ten days, the long-term stability of the DFT up to one year remained stable in the devices with the "active-can" lead system.