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Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11thInternational Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.

Several prospective randomized clinical trials have reported that atrial-based “physiological” pacing is associated with a lower incidence of paroxysmal and permanent atrial fibrillation than single-chamber ventricular pacing in patients with conventional pacemaker indication. Whether atrial pacing itself is antiarrhythmic remains still uncertain. By contrast, right ventricular pacing is considered to beget atrial fibrillation, even in preserved AV synchrony during dual-chamber pacing. A number of clinical trials investigated the impact of sitespecific atrial pacing and advanced atrial pacing algorithms on the secondary prevention of atrial fibrillation. Multisite pacing (dual-site right atrial or biatrial pacing) was demonstrated to add only minimal benefit for the prevention of atrial fibrillation. By contrast, in some studies septal pacing and specific atrial pacing algorithms were reported to reduce the recurrence of atrial fibrillation in selected patients. At present, however, it remains unclear how to identify these patients. In clinical practice, the effectiveness of specific atrial pacing algorithms and/or septal pacing has to be tested out in the individual case. These therapeutic options should be considered in patients with a conventional indication for antibradycardia pacing and, additionally, symptomatic atrial fibrillation.

Thromboemoblism is the most feared complication of atrial fibrillation. Percutaneous left atrial appendage occlusion is a new interventional procedure for reducing thromboembolic risk in patients with atrial fibrillation. The paper reports of a post mortem analysis of the device demonstrating that one year after implantation the atrial surface of the device is completely covered by neo-endothelium and the device occludes the appendage completely.

Abstract

The history of interventional electrophysiology is long and fascinating. In the beginning, there is not simply the anatomy and physiology of the heart, but also analysis of the pulse, which indicates the activity of the heart. The analysis of the (peripheral) pulse as a mechanical expression of heart activity goes back several millennia. In China, in 280 B.C., Wang Chu Ho wrote ten books about the pulse. The Greeks called the pulse “sphygmos”, and the sphygmology thus deals with a theory of this natural occurrence. In Roman times, Galen interpreted the various types of pulse according to the widespread presumption of the time, that each organ in every disease has its own form of pulse. The basic tool for arrhythmia diagnosis became the electrocardiography introduced by Willem Einthoven who obtained the first human electrogram 1902 in Leiden, The Netherlands. The growing clinical importance of electrical cardiac stimulation has been recognized and renewed as Zoll (1911–1999) in 1952 reported a successful resuscitation in cardiac standstill by external stimulation. Meanwhile all over the world, millions of patients with cardiac arrhythmias have been treated with pacemakers in the last 45 years. The concept of a fully automatic implantable cardioverter-defibrillator system (ICD) for recognition and treatment of ventricular tachyarrhythmias was first suggested in 1970. The first implantation of the device in a human being was performed in February 1980. Further developments concern atrial and atrioventricular defibrillators, radiofrequency ablation, laser therapy and advanced antiarrhythmic surgery, new antiarrhythmic drugs and sophisticated devices for preventive pacing. The advances in the field of diagnostic and therapeutic application of pharmacologic and electrical tools as well as alternative methods will continue as rapidly as before in order to give us further significant aid in taking care of the patient.

Background:Electrical isolation of pulmonary veins (PV's) is crucial to achieve success in catheter ablation for trigger elimination in focal atrial fibrillation (AF). To guide ostial PV radiofrequency (RF) delivery, it is necessary to identify the electrical breakthrough (EBT) between PV and left atrium. For this purpose, coronary sinus (CS) fixed rate pacing is commonly used. This study evaluated, whether CS extrastimulus pacing is superior in identifying the EBT area as compared to fixed rate pacing. Methods:In 9 patients (51 ± 10 years) undergoing a left sided electrophysiological study for AF ablation, 25 PV's (10 right and 15 left-sided PV's) were mapped using a 4 French fixed-wire catheter with eight 6 mm coiled Platinum electrodes in a distal looped configuration (Revelation Helix, Cardima Inc.). For mapping and ablation the electrode loop was positioned in the PV ostium rectangular to the longitudinal PV axis. EBT area was identified as those electrodes indicating the earliest PV signals during CS pacing. We measured number of EBT electrodes and time between EBT and the latest activated bipoles at the electrode loop during fixed rate and extrastimulus pacing. The reduction of two or more EBT electrodes was defined as a significant benefit in EBT identification. Results:In 22 of 25 PV's mapped PV potentials could be observed. Performing fixed rate pacing the EBT area was identified in a mean of 4.2 ± 1 electrodes, whereas using extrastimulus pacing, EBT area could be significantly reduced to 2.3 ± 0.8 electrodes. The time between EBT and latest electrode activated increased from 14 ± 7 ms to 22 ± 10 ms indicating an intrapulmonary conduction delay during extrastimulus pacing. In 13 of 22 PV's mapped (59%), extrastimulus pacing was beneficial in the identification of the EBT, as the primary target for RF delivery. Conclusions:CS extrastimulus pacing induces intra-PV decremental conduction properties allowing one to identify a more localised and smaller EBT area as the primary target for RF delivery. Performing PV ablation to treat focal AF, extrastimulus maneouvers allow to unmask the “true” EBT and thus may help to limit intrapulmonary RF delivery.

The pharmacological and ablative hybrid-therapy can be applied in patients who convert from atrial fibrillation to atrial flutter during drug therapy. This type of hybrid approach consists of catheter ablation of the induced AFl and continuation of the AFl-inducing drug to prevent from atrial fibrillation recurrencies. The purpose of this hybrid therapy is to obtain sinus rhythm or at least to decrease the frequency and severity of AF-episodes. The current study status proves that this form of hybrid therapy is an effective tool in selected patients to suppress atrial fibrillation and to improve quality of life even in those patient who still exhibit atrial fibrillation episodes. Die pharmakologische und ablative Hybridtherapie des Vorhofflimmerns ist bei ausgewählten Patienten möglich, die eine Konversion von Vorhofflimmern in Vorhofflattern unter Antiarrhythmikaeinfluss aufweisen. Im Rahmen dieser Form von Hybridtherapie wird das Antiarrhythmika-induzierte typische Vorhofflattern einer Katheterablation unterzogen und die Vorhofflatter-induzierende Medikation zur Rezidivprophylaxe anschließend fortgeführt. Ziel dieser Behandlung ist es, entweder Vorhofflimmerfreiheit oder aber zumindest eine reduzierte Rezidivrate von Vorhofflimmern zu erzielen. Die bisherigen Studien belegen, dass die ablative und pharmakologische Hybridtherapie auch eine langfristig effektive Therapiemöglichkeit darstellt. Obwohl durch die Anwendung einer Hybridtherapie im Langzeitverlauf oftmals kein völliges Ausbleiben symptomatischer Vorhofflimmerepisoden erzielt werden kann, wird dennoch eine signifikant niedrigere Vorhofflimmerrezidivrate, eine Verbesserung der AF-Symptome sowie eine Steigerung der Lebensqualität beobachtet.

The authors review the history of atrial fibrillation, the most frequent clinically observed cardiac arrhythmia. A French “clinicopathologist”, Jean Baptist de Sénac (1693–1770), was the first who assumed a correlation between “rebellious palpitation” and a stenosis of the mitral valve. From an analysis of simultaneously recorded arterial and venous pressure curves, the Scottish Sir James Mackenzie (1853–1925) demonstrated that a presystolic awave cannot be seen on the jugular phlebogram during “pulsus irregularis perpetuus”. The first human ECG depicting atrial fibrillation was published by Willem Einthoven (1860–1927) in 1906. The proof of a direct connection between absolute arrhythmia and auricular fibrillation was established by two Viennese physicians, Rothberger and Winterberg. The major discoveries relating to the pathomechanism and the clinical features of atrial fibrillation in the 20thcentury stemmed from the scientific activities of Karel Frederik Wenckebach, Sir Thomas Lewis, Gordon Moe, and Maurits Allessie. Der französische klinische Pathologe Jean Baptist de Sénac (1693–1770) war der erste, der eine Korrelation zwischen den „rebellischen Palpitationen” und der Mitralstenose vermutete. Aufgrund der Analysen simultan registrierter arterieller und venöser Druckkurven beim Pferd konnte der berühmte schottische Arzt Sir James Mackenzie (1853–1925) zeigen, dass die präsystolische a-Welle im jugulären Phlebogramm während eines „pulsus irregularis perpetuus” nicht nachweisbar ist. Die erste elektrokardiographische Registrierung von Vorhofflimmern wurde 1906 von Willem Einthoven (1860–1927) veröffentlicht. Der Nachweis einer direkten Beziehung zwischen absoluter Arrhythmie und Vorhofflimmern („aurikuläre Fibrillation”) wurde 1909 von den beiden Wiener Klinikern Rothberger und Winterberg geführt. Die entscheidenden Erkenntnisse des 20. Jahrhunderts über den Pathomechanismus und das klinische Bild des Vorhofflimmerns sind den Wissenschaftlern Karel Frederik Wenckebach, Sir Thomas Lewis, Gordon Moe und Maurits Allessie zu verdanken.

BackgroundAlthough specific antiplatelet drugs are well-established and effective in atherosclerosis prevention, recent clinical trials have also shown that use of angiotensin-converting enzyme (ACE) inhibitors results in a decrease in cardiovascular events. Therefore, in this study, we sought to assess the coagulative activity of patients with cardiovascular disease grouped for treatment with either ACE inhibitors, aspirin, clopidogrel/aspirin, or none of these medications. MethodsBlood samples from 303 patients with cardiovascular disease were analyzed with whole-blood aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the aggregatory agents adenosine diphosphate (ADP) or collagen. ResultsAs the central finding, platelet aggregation was attenuated by ACE inhibitors and by aspirin or clopidogrel/aspirin, which was indicated by a lower impedance increase compared with no medication. With ACE inhibition, platelet aggregation decreased by 33% (P=.042) after ADP induction. No significant antithrombotic effect was seen with aspirin alone (17%, P= 1.0), whereas a decrease in ADP-induced platelet aggregation was extensive with clopidogrel/aspirin (85%, P=.001). After collagen induction, platelet aggregation was reduced by 16% (P=.028) in the presence of ACE inhibitor therapy, whereas inhibition with aspirin and clopidogrel/aspirin was 23% (P=.004) and 35% (P=.026), respectively, compared with participants who were not treated. ConclusionsThese ex vivo data on whole-blood aggregometry provide direct evidence that ACE inhibitors decrease platelet aggregation, whereas aspirin and clopidogrel are confirmed as established antithrombotics. Pleiotropic effects of ACE inhibition on platelet function may contribute to the clinical benefit observed with this drug class on major cardiovascular end points. (Am Heart J 2003;145:343-8.)

Inflammatory mechanisms are central in human atherosclerosis. Although C-reactive protein (CRP) as a serum marker is highly predictive for cardiovascular events, the intimal expression of CRP in clinically relevant coronary lesions is unknown, in particular in acute coronary syndromes (ACS). Shown by reduced CRP serum values, statins have antiinflammatory and plaque-stabilizing effects. In the present study, the presence of CRP in coronary atheromas with ACS versusstable angina (SA) as well as its possible modification by chronic statin medication was assessed. ??Coronary atherectomy probes from 90 primary stenoses were immunohistochemically analyzed with regard to the presence and the localization of CRP. Intimal results of patients with ACS (n=36), categorized according to the Braunwald classification, were compared with those of patients with SA (n=54). ??In 40 of 90 lesions (44%), immunoreaction specific for CRP was observed demonstrating a mean CRP expression of 1.7%. CRP was focally localized in a maximum of 69% of all plaque cells, the most in macrophages/foam cells, infrequently in smooth muscle cells. CRP-positive plaques showed more thrombus than plaques without CRP (63% vs 41%). Intact non-atherosclerotic control tissue revealed no signaling. As a central finding, intimal presence and expression were higher (each p<0.001) with ACS (69% and 3.1%, respectively) compared to SA (28% and 0.8%, respective). Subgroup analysis of target lesions associated with ACS according to the clinical Braunwald classification showed an increase of intimal CRP with classes I–III. In the presence of statin medication, intimal CRP was significantly lower than that without statin therapy (29 and 1.3%, vs 61 and 2.6%, respectively; p<0.01), in particular in the subgroup of ACS patients. ??Intimal CRP is frequently found in coronary primary stenoses, very often with macrophages/foam cells, and shows a highly significant prevalence with ACS. In this subgroup of patients, statin therapy is associated with significantly reduced intimal CRP. Our in situfindings as shown might explain the well-known serum constellations with statin therapy. Inflammationsvorgänge haben zentrale Bedeutung bei humaner Arteriosklerose. C-reaktives Protein (CRP) als Serum-Marker zeigt prädiktiven Wert für kardiovaskuläre Ereignisse, unbekannt ist dagegen die intimale Expression von CRP in klinisch relevanten Koronarläsionen, insbesondere bei akutem Koronarsyndrom (ACS). Ausweislich verminderter CRP-Serumwerte, wirken Statine antiinflammatorisch und plaquestabilisierend. In der vorliegenden Studie wurde die Präsenz von CRP in koronaren Atheromen bei ACS versusstabiler Angina (SA) sowie deren mögliche Modifikation bei bestehender Statinmedikation untersucht. ??Koronare Atherektomieproben aus 90 Primärstenosen wurden immunhistochemisch auf die Präsenz und Lokalisation von CRP analysiert. Intimale Befunde von Patienten mit ACS (n=36), kategorisiert nach der Braunwald-Klassifikation, wurden mit denen von Patienten mit SA (n=54) verglichen. ??In 40 von 90 Zielläsionen (44%) war eine Immunreaktion gegen CRP bei einer durchschnittlichen CRP-Expression von 1,7% nachweisbar. CRP war fokal in maximal 69% aller Plaquezellen, meist in Makrophagen/Schaumzellen, selten in glatten Muskelzellen lokalisiert. CRP-positive Plaques wiesen häufiger Thrombusanteile als Plaques ohne CRP-Nachweis (63 vs. 41%) auf. Intaktes, nicht arteriosklerotisch erkranktes Kontrollgewebe zeigte keine Signale. Als zentrale Befunde waren intimale Präsenz und Expression von CRP höher (jeweils p<0,001) bei ACS (69 bzw. 3,1%) gegenüber SA (28 bzw. 0,8%). Die Subgruppenanalyse der mit ACS assoziierten Zielläsionen nach der Braunwald-Klassifikation ergab eine Zunahme von intimalem CRP mit dem klinischen Schweregrad (Klasse I bis III). Bei Statineinnahme war der intimale CRP-Nachweis deutlich geringer als bei fehlender Therapie (29% bzw. 1,3% vs. 61% bzw. 2,6%; p<0,01), insbesondere in der Subgruppe der Patienten mit ACS. ??Intimales CRP ist häufig in koronaren Primärstenosen, meist mit Makrophagen/Schaumzellen, nachweisbar und zeigt eine hochsignifikante Prävalenz bei akutem Koronarsyndrom. Statintherapie ist hier mit signifikant geringeren intimalen CRP-Werten assoziiert. Die aktuellen in situBefunde könnten bekannte Serumkonstellationen bei Statintherapie erklären.

Background:Atrial fibrillation (AF) can be cured in a subgroup of patients performing catheter ablation and eliminate trigger arrhythmias mainly originating in the pulmonary veins (PV's). Case Report:This case report describes the use of a novel catheter design combining both, circumferential mapping and radiofrequency delivery capabilities to perform pulmonary vein ablation in patients with focal AF. It could be demonstrated that this catheter was able to eliminate pulmonary vein potentials in a single left atrial catheter technique without acute evidence for PV stenosis. In two PV's of a second patient, where the Helix catheter was placed in a very ostial position, it was not possible to completely eliminate the PV signal component of the ostial electrogram. Long-term follow-up with AF recurrence documentation will clarify whether ostial PV signal amplitude reduction may serve as an acceptable procedural endpoint. Conclusion:PV potential elimination is feasible using this novel catheter design; safety and long-term efficacy of this single catheter approach will be evaluated in a multicenter study (BITMAPstudy: Breakthrough and Isolation Trial: Mapping and Ablation of Pulmonary Veins).

Transesophageal echocardiographic (TEE) guidance of cardioversion in patients with atrial fibrillation is an alternative method to conventional anticoagulation. Although TEE is considered the gold standard for excluding left atrial (LA) thrombi, in some patients dense spontaneous echo contrast (SEC) and artifacts may hamper the identification or exclusion of LA thrombi. Often those patients are refused cardioversion. The purpose of this study was to determine whether the application of echo contrast (Optison, Mallinckrodt, San Diego, Calif) facilitates the exclusion of LA appendage thrombi in this patient group and allows for safer cardioversion. Forty-one patients with atrial fibrillation and dense SEC or inconclusive TEE findings were given echo contrast. Fourteen patients with sinus rhythm served as control participants. Echo contrast completely reduced artifacts in 13 of 22 patients. In 12 of 19 patients with SEC, the LA appendage was completely filled after the application of echo contrast and, thus, SEC was completely suppressed. In 13 of 41 patients, it was filled incompletely and in 9 of 41 patients, a new mass resembling a thrombus was detected. In total, of 25 of 41 patients with inconclusive TEE findings an atrial thrombus was definitively excluded. Those patients underwent cardioversion. None of those patients had a cerebral embolic complication as assessed by cranial magnetic resonance imaging. Thus, the application of echo contrast may facilitate the TEE exclusion of LA appendage thrombi and, hence, improve the safety of TEE-guided cardioversion. (J Am Soc Echocardiogr 2002;15:1256-61.)

Die Therapie von Herzrhythmusstörungen hat eine lange und faszinierende Vorgeschichte. Diese reicht – bezogen auf die Pulsbeobachtung – mehrere Jahrtausende zurück und führte über eine höchst wechselvolle Geschichte erst relativ spät zu dem heutigen Kenntnisstand. Die Rhythmologie hat in den 75 Jahren des Bestehens unserer Fachgesellschaft eine überaus dynamische Entwicklung erfahren. Dies gilt gleichermaßen für die Diagnostik wie für die medikamentöse Behandlung und die vielfältigen elektrotherapeutischen Verfahren. Über die Synthetisierung zahlreicher antifibrillatorischer Arzneimittel führte die Entwicklung zu neuen antiarrhythmischen Wirkstoffen, wie Amiodaron, Flecainid, Tocainid sowie dem vielseitigen Betarezeptorenblocker Sotalol und Adenosin (i.v.) als Alternative zu Verapamil bei supraventrikulären Tachykardien. In klinischer Erprobung bzw. vor der Markteinführung stehen innovative Substanzen wie Azimilide, Dofetilide, Dronedarone, Ibutilide, Tediasamil und andere. Neu ist die sogenannte Hybridtherapie, die sich z.B. durch kombinierte medikamentöse und ablative Behandlung supraventrikulärer Tachykardien (Vorhofflimmern/Vorhofflattern) als hilfreich erwiesen hat. Der aktuelle Stand der Schrittmachertechnologie wird durch frequenzadaptive „biologische“ Schrittmacher repräsentiert. Den antibradykarden Systemen stehen Aggregate gegenüber, die bei anderweitig therapieresistenten schnellen Herzrhythmusstörungen eingesetzt werden können; entweder als antitachykarde Schrittmachersysteme (einschließlich präventiver Stimulationsalgorithmen bei Vorhofflimmern) und/oder in Form von automatischen implantierbaren Defibrillatoren. Neben diesen symptomatischen elektrotherapeutischen Maßnahmen bestehen kurative Möglichkeiten in der Ablation bzw. Koagulation erregungsleitender Strukturen bzw. arrhythmogener Bezirke des Herzens durch spezielle Elektrodenkatheter und Mappingverfahren, die in den nächsten Jahren noch zu perfektionieren sind. Große Erwartungen knüpfen sich an die Gen- und Zelltherapie bzw. Stammzelltechnologie mono- oder polygenetisch begründeter rhythmologischer Krankheitsbilder (Long QT-Syndrom, Brugada-Syndrom etc.). The history of cardiac rhythm disorders including antiarrhythmic drugs and electrotherapeutical tools is long and fascinating. In the beginning, there was not simply the anatomy and physiology of the heart, but also analysis of the pulse, which indicates the activity of the heart. Thus, like any other field of medicine, the study of arrhythmias has a distinctive past. Our current level of knowledge is not the result of a straight, linear progression any more than there is a static, established, monolithic body of thought dominating this field. Instead, our knowledge of arrhythmias today is the result of many competitive, sometimes serendipitous, scientific realizations, of which a few proved useful enough to pursue and eventually led to real advancements. Looking at the worldwide development of rhythmology it can be said that considerable contributions came from Germany in the last few centuries. Arrhythmology – past, present and future – includes clearly German investigators as pioneers of the field. The growing clinical importance of electric cardiac stimulation has been recognized and renewed as Zoll in 1952 described a successful resuscitation in cardiac standstill by external stimulation. The concept of a fully automatic implantable cardioverter-defibrillator system for recognition and treatment of ventricular flutter/fibrillation was first suggested in 1970. The first implantation of the device in a human being was performed in February 1980. By early 1997, 17 years after the first human implantation more than 100000 ICD systems had been implanted worldwide. Further developments concern new pharmacological compounds, modern cardioverter-defibrillators, radiofrequency ablation, particularly pulmonary vein ablation in atrial fibrillation, innovative pacemakers including preventive pacing techniques, probably laser therapy and perhaps the automatic implantable pharmacological defibrillator. The advances in the field of therapeutic application of pharmacologic and electrical means as well as alternative methods will continue as rapidly as before in order to give us further significant aid in taking care of the patient.

Restenosis post angioplasty remains the major limitation of several therapeutic interventions including stent implantation. This explains the ongoing interest in its basic pathogenic mechanisms and factors. The aim of the present study was to assess the localization and maximal expression of Bcl-2, a central anti-apoptotic protooncogene, and of heat shock protein 47 (HSP47), a marker of early collagen synthesis, in the context with hyperplastic neointima formation as well as concomitant transmural remodeling processes following angioplasty. 0, 4, 24 and 48 hours, 4, 7 and 14 days post balloon traumatization by use of a rat carotid artery model, specific vascular wall compartments were evaluated concerning area, cell density as well as Bcl-2 and HSP47 expression by immunohistochemistry and morphometry, supplemented by electron microscopy (TEM). Neointimal cell accumulation was detected 4 days post angioplasty, characterized by luminal cells adherent to the internal elastic lamina, associated with maximal Bcl-2 and HSP47 expression amounting to 49% and 41%, respectively. With ongoing neointimal formation, a luminal prevalence of both key determinants and a decreasing expression in basal neointimal areas were found. In the media, a temporally reduced cell density was observed significant at 48 hours post trauma. Constitutive HSP47 expression of the media was constant during the entire observation period, whereas sparse Bcl-2 signalling was induced post angioplasty maximal on day 2 with 3% and on day 14 with 5%. The adventitia demonstrated a transient structural separation between day 4 and 7, exhibiting an inner layer with sparse cellularity and an outer layer with extremely high cell density as well as pronounced neovascularization. In this outer adventitia layer, a high frequency of signals for both Bcl-2 and HSP47 were observed amounting to 29% and 57%, respectively. Complementary TEM analysis gave no evidence of transmural migratory events propagated by adventitial cells and thereby supports early neointimal formation by luminal cell recruitment and marked co-expression of anti-apoptotic Bcl-2 and matrix-generating HSP47 as important survival factors. Clinical implications of these findings may be seen in the integration of proapoptotic substances with temporal efficacy in order to prevent restenosis, e.g., by use of coated stents. Die Restenose bleibt diewesentliche Limitierung verschiedener interventioneller Therapiemassnahmen, auch der Stentimplantation. Dies erklärt das unverändert große Interesse an ihren zugrundeliegenden Pathogenesemechanismen und -faktoren. Ziel der vorliegenden Arbeit war es, Lokalisation und Expressionsmaxima von Bcl-2, einem zentralen anti-apoptotischen Protoonkogen, und von Hitzeschockprotein 47 (HSP47), einem Marker früher Kollagensynthese, im Kontext mit der Formierung hyperplastischer Neointima und parallelen transmuralen Umbauprozessen nach Angioplastie zu untersuchen. 0, 4, 24 und 48 Stunden, 4, 7 und 14 Tage nach Ballontrauma wurden am Modell der A. carotis der Ratte einzelne Gefässwandkompartimente hinsichtlich Fläche, Zelldichte sowie Bcl-2- bzw. HSP47-Expression (immun-)histochemisch und morphometrisch evaluiert, ergänzt durch Elektronenmikroskopie (TEM). Neointimale Zellakkumulation war bereits 4 Tage nach Angioplastie nachweisbar, ausgewiesen durch Adhäsion luminaler Zellen an die Lamina elastica interna, assoziiert mit maximaler Bcl-2- sowie HSP47-Expression von 49% bzw. 41% aller gezählten Zellen. Mit zunehmender Neointima demarkierte sich eine lumennahe Prävalenz beider Zieldeterminanten mit abnehmender Expression zu basalen Arealen. In der Media fand sich eine temporäre, lediglich 48 Stunden nach Trauma signifikant verminderte Zelldichte. Die konstitutive HSP47-Expression der Media war im gesamten Beobachtungszeitraum konstant, während für Bcl-2 nach Angioplastie wenige Signale nachweisbar waren mit Maximalwerten von 3% am Tag 2 und 5% am Tag 14. Die Adventitia wies eine transiente strukturelle Zweiteilung zwischen Tag 4 und 7 auf mit einer inneren, extrem zellarmen Schicht und einer äußeren Schicht bei sehr hoher Zelldichte sowie ausgeprägter Neovaskularisation. In dieser äußeren Adventitia waren hohe Signaldichten von Bcl-2 und HSP47 bis zu 29% bzw. 57% nachweisbar. Komplementäre TEM-Untersuchungen ergaben keine Hinweise auf die transmurale Migration adventitialer Zellen und stützen somit eine frühe Neointimaformierung durch luminale Zellrekrutierung bei hoher Co-Expression des anti-apoptotischen Bcl-2 und des Matrix-generierenden HSP47 als wichtige Überlebensfaktoren. Klinische Implikationen dieser Befunde könnten in der Integration befristet pro-apoptotischer Substanzen zur Restenoseprävention, z.B. in beschichteten Stents, liegen.

Restenosis post angioplasty remains the major limitation of several therapeutic interventions including stent implantation. This explains the ongoing interest in its basic pathogenic mechanisms and factors. The aim of the present study was to assess the localization and maximal expression of Bcl-2, a central anti-apoptotic protooncogene, and of heat shock protein 47 (HSP47), a marker of early collagen synthesis, in the context with hyperplastic neointima formation as well as concomitant transmural remodeling processes following angioplasty. 0, 4, 24 and 48 hours, 4, 7 and 14 days post balloon traumatization by use of a rat carotid artery model, specific vascular wall compartments were evaluated concerning area, cell density as well as Bcl-2 and HSP47 expression by immunohistochemistry and morphometry, supplemented by electron microscopy (TEM). Neointimal cell accumulation was detected 4 days post angioplasty, characterized by luminal cells adherent to the internal elastic lamina, associated with maximal Bcl-2 and HSP47 expression amounting to 49% and 41%, respectively. With ongoing neointimal formation, a luminal prevalence of both key determinants and a decreasing expression in basal neointimal areas were found. In the media, a temporally reduced cell density was observed significant at 48 hours post trauma. Constitutive HSP47 expression of the media was constant during the entire observation period, whereas sparse Bcl-2 signalling was induced post angioplasty maximal on day 2 with 3% and on day 14 with 5%. The adventitia demonstrated a transient structural separation between day 4 and 7, exhibiting an inner layer with sparse cellularity and an outer layer with extremely high cell density as well as pronounced neovascularization. In this outer adventitia layer, a high frequency of signals for both Bcl-2 and HSP47 were observed amounting to 29% and 57%, respectively. Complementary TEM analysis gave no evidence of transmural migratory events propagated by adventitial cells and thereby supports early neointimal formation by luminal cell recruitment and marked co-expression of anti-apoptotic Bcl-2 and matrix-generating HSP47 as important survival factors. Clinical implications of these findings may be seen in the integration of proapoptotic substances with temporal efficacy in order to prevent restenosis, e.g., by use of coated stents. Die Restenose bleibt diewesentliche Limitierung verschiedener interventioneller Therapiemassnahmen, auch der Stentimplantation. Dies erklärt das unverändert große Interesse an ihren zugrundeliegenden Pathogenesemechanismen und -faktoren. Ziel der vorliegenden Arbeit war es, Lokalisation und Expressionsmaxima von Bcl-2, einem zentralen anti-apoptotischen Protoonkogen, und von Hitzeschockprotein 47 (HSP47), einem Marker früher Kollagensynthese, im Kontext mit der Formierung hyperplastischer Neointima und parallelen transmuralen Umbauprozessen nach Angioplastie zu untersuchen. 0, 4, 24 und 48 Stunden, 4, 7 und 14 Tage nach Ballontrauma wurden am Modell der A. carotis der Ratte einzelne Gefässwandkompartimente hinsichtlich Fläche, Zelldichte sowie Bcl-2- bzw. HSP47-Expression (immun-)histochemisch und morphometrisch evaluiert, ergänzt durch Elektronenmikroskopie (TEM). Neointimale Zellakkumulation war bereits 4 Tage nach Angioplastie nachweisbar, ausgewiesen durch Adhäsion luminaler Zellen an die Lamina elastica interna, assoziiert mit maximaler Bcl-2- sowie HSP47-Expression von 49% bzw. 41% aller gezählten Zellen. Mit zunehmender Neointima demarkierte sich eine lumennahe Prävalenz beider Zieldeterminanten mit abnehmender Expression zu basalen Arealen. In der Media fand sich eine temporäre, lediglich 48 Stunden nach Trauma signifikant verminderte Zelldichte. Die konstitutive HSP47-Expression der Media war im gesamten Beobachtungszeitraum konstant, während für Bcl-2 nach Angioplastie wenige Signale nachweisbar waren mit Maximalwerten von 3% am Tag 2 und 5% am Tag 14. Die Adventitia wies eine transiente strukturelle Zweiteilung zwischen Tag 4 und 7 auf mit einer inneren, extrem zellarmen Schicht und einer äußeren Schicht bei sehr hoher Zelldichte sowie ausgeprägter Neovaskularisation. In dieser äußeren Adventitia waren hohe Signaldichten von Bcl-2 und HSP47 bis zu 29% bzw. 57% nachweisbar. Komplementäre TEM-Untersuchungen ergaben keine Hinweise auf die transmurale Migration adventitialer Zellen und stützen somit eine frühe Neointimaformierung durch luminale Zellrekrutierung bei hoher Co-Expression des anti-apoptotischen Bcl-2 und des Matrix-generierenden HSP47 als wichtige Überlebensfaktoren. Klinische Implikationen dieser Befunde könnten in der Integration befristet pro-apoptotischer Substanzen zur Restenoseprävention, z.B. in beschichteten Stents, liegen.

Die Restenose nach Angioplastie stellt weiterhin eine erstrangige Limitierung interventioneller Therapieverfahren dar. Verschiedene Evidenzen zeigen, dass die Expression von Promotoren myofibroblastoider Aktivität von der Neoadventitia zur Neointima wandert. Brachytherapie vermag die Aktivität (Proliferation, Migration) vaskulärer Zellen zu inhibieren, die intimale Rekrutierung dieser Zellen zu vermindern, und beeinflusst das vaskuläre Remodeling positiv, indem die adventitiale Konstriktion im Bereich der Gefäßverletzung verhindert wird. Diese Brachytherapie-Effekte sind dosisabhängig. Klinische und experimentelle Daten demonstrieren, dass die Restenose durch die Balance von arteriellem Remodeling und intimaler Hyperplasie determiniert wird. Offenbar spielt brachytherapieinduziertes positives Remodeling die entscheidende Rolle bei der Vergrößerung des luminalen Durchmessers nach PTCA und, im Falle von Unterdosierung bzw. Dosisabfall, als Ursache negativer Edge-Effekte. Für den klinischen Verlauf wahrscheinlich bedeutungsvoll und bisher eher unterschätzt sind Heilungs-Defekte, endotheliale Dysfunktion und Stent-Gefäßwand-Fehllage, die beitragen könnten zu später Thrombose und verzögerter intimaler Hyperplasie im Langzeitverlauf nach intrakoronarer Brachytherapie. Post-angioplasty restenosis is a major limitation of interventional cardiology. A large body of evidence reveals that expression of myofibroblast activity promoters moves progressively from the neoadventitia to the neointima. Brachytherapy inhibits vascular cell activity (proliferation, migration), mitigates recruitment of intimal cells, and shows a favorable prophylactic effect on late vascular remodeling by preventing adventitial constriction at the injured site. These effects of brachytherapy are dose related. Clinical and experimental data demonstrate that restenosis is determined by the balance between arterial remodeling and intimal hyperplasia. Apparently, brachytherapy-induced positive remodeling plays the principal role in increasing the luminal diameter after PTCA and, in case of a lower dose or dose fall-off, to cause detrimental edge effects. With regard to clinical course, healing defects, endothelial dysfunction and stent-vessel wall malapposition are apparently important and possibly underestimated features of vascular pathology, since they may contribute to late thrombosis and delayed intimal hyperplasia in long-term course after intracoronary brachytherapy.

Die Schrittmachertherapie in Form der frequenzadaptiven ventrikulären Demand-Stimulation stellt bei allen Formen der symptomatischen Bradyarrhythmia absoluta eine etablierte und bewährte Behandlung dar. Bei paroxysmalem oder persistierendem Vorhofflimmern sollte im Falle einer Zwei-Kammer-Stimulation das implantierte Aggregat über einen automatischen Betriebsartwechsel (“Mode Switch”) verfügen, zum einen, um eine schrittmachervermittelte rasche Überleitung von Vorhofflimmern zu verhindern, vor allem aber, um diesen Patienten außerhalb ihrer Paroxysmen alle Vorteile der Zwei-Kammer-Stimulation zukommen zu lassen, wie verbesserte Hämodynamik und Frequenzadaptation, niedrigerer Vorhofflimmerprogress und geringere Thromboembolierate gegenüber der Ein-Kammer-Stimulation im Sinusrhythmus. Zukunftsperspektive:Als neues Einsatzgebiet der Schrittmachertherapie wird die präventive Stimulation erprobt, d. h. die Anwendung von Stimulationsmanövern mit dem Ziel das Auftreten von Vorhofflimmern zu verhindern. Zahlreiche methodische Ansätze, wie Varianten des atrialen Stimulationsortes (septale oder Bachmann-Bündel-nahe Stimulation), das “Multisite Pacing”, präventive Algorithmen mit konventioneller oder varianter Vorhofelektrodenlage sowie Hybrid- und Triplekonzepte sind hier bereits technisch realisiert worden. Da alle diese Interventionen unter Berücksichtigung der großen intra- und interindividuellen Variabilität der Vorhofflimmerinduktion antiarrhythmisch, aber prinzipiell auch proarrhythmisch wirken können, ist die Studienlage zur Beurteilung der Therapieeffizienz von besonderer Bedeutung. Hier erscheint die septale oder Bachmann-Bündel-nahe Stimulation sowie die Anwendung präventiver Stimulationsalgorithmen als aussichtsreichste Interventionsform, zumal erste prospektive Untersuchungen einen signifikant günstigen Einfluss auf die Entwicklung von permanentem Vorhofflimmern wie auch die Vorhofflimmerrezidivneigung ergeben haben. Schlussfolgerungen:Dies sollte Motivation sein, bei Patienten mit konventioneller Schrittmacherindikation und symptomatischem Vorhofflimmern den Einsatz einer z. B. spetalen Eletrodenlage oder präventiver Stimulationsalgorithmen in Erwägung zu ziehen.Die präventive Stimulation stellt aber aufgrund ihrer nur inkompletten Therapieerfolge und des relevanten Anteils an “Nonrespondern” zum jetzigen Zeitpunkt sicher noch keine “frühe” Eskalationsstufe in der Behandlung von Vorhofflimmern bei Patienten ohne stimulationsbedürftige Bradykardie dar. Pacing therapy is well established in all cases of symptomatic bradyarrhythmic atrial fibrillation. In paroxysmal or persistent atrial fibrillation, the implanted dual chamber pacemaker device should incorporate an automatic mode switching algorithm. Mode switch in case of atrial fibrillation detection avoids pacemaker mediated rapid ventricular pacing during an atrial tachyarrhythmia and allows to perform dual chamber pacing during phases of sinus rhythm which is the preferable mode due to improved hemodynamics, rate adaptation, lower progress in atrial fibrillation burden and a lower rate of thromboembolic events as compared to ventricular pacing. Perspektive:The possibility to prevent from atrial fibrillation recurrencies by pacing is currently under investigation. Various methodological approaches, for example multisite or alternate single site pacing, preventive pacing algorithms or hybrid- and even triple-therapy concepts are used for that purpose. Due to the theoretical point of view, that all these pacing interventions may reduce atrial fibrillation but also have the potential to act in a proarrhythmic manner, the data from adequately designed trials is of major importance: Septal pacing and preventive pacing algorithms seem to have a beneficial effect in a limited number of so far available studies, Conclusion:In clinical practice, preventive pacing and/or placement of the atrial lead in a septal position should therefore be available in those patients with a conventional pacing indication in addition to symptomatic recurrent atrial fibrillation. Preventive pacing is so far with a significant and not-predictable amount of non-responders no “early” stage of therapy in patients with recurrent symptomatic atrial fibrillation and no additional conventional pacing indication.

Left ventricular noncompaction is an unclassified cardiomyopathy characterized by an excessively prominent trabecular meshwork due to an arrest in myocardial morphogenesis. We report on a 51-year-old female patient with abnormal myocardial trabeculations associated with a congenital mitral valve stenosis post commissurotomy at the age of 14. In the present case report, clinical manifestation of the disorder included impaired left ventricular systolic function and atrial fibrillation. Noncompaction was diagnosed by echocardiography and levocardiography. In addition, a review of the literature on this rare disorder is presented. Linksventrikuläres Noncompaction ist eine unklassifizierte Kardiomyopathie, die durch ein exzessiv prominentes trabekuläres Netzwerk charakterisiert ist und die auf einen Arrest in der myokardialen Morphogenese zurückgeführt werden kann. Wir berichten über eine 51-jährige Patientin mit abnormaler myokardialer Trabekularisierung, assoziiert mit einer angeborenen Mitralklappenstenose und Z.n. Kommissurotomie im Alter von 14 Jahren. Im vorliegenden Fallbericht manifestierte sich Noncompaction mit einer verminderten linksventrikulären systolischen Funktion und Vorhofflimmern. Die Diagnosefindung erfolgte durch Echokardiographie und Lävokardiographie. Zusätzlich wird eine Literaturübersicht über diese seltene Anomalie gegeben.

Recent evidence suggests a causal relationship between inflammatory as well as infectious pathomechanisms and valvular degeneration. Based on the concept of chronic Chlamydia pneumoniaeand cytomegalovirus (CMV) infections, and of variable stressors working on valvular microecology, the present study sought to assess the presence of the specific chlamydial heat shock protein (cHSP) 60, of CMV, of macrophages and of the human homologue hHSP60. ??Serial sections of high-grade degenerated native (n=16) and prosthetic (n=6) aortic valves were analyzed by immunohistochemistry for the presence of these determinants. Degenerated aortic valves revealed prevalence of Chlamydia pneumoniaein 41% (10 of 22) and CMV in 73% (16 of 22), while immunoreactive hHSP60 was present in 64% (14 of 22) and CD68 in 86% (19 of 22). Chlamydial HSP60, CMV and hHSP60 were predominantly found in valvular fibrosa; CMV showed a second predilection site at the ventricular luminal border. Both microorganisms revealed a strong correlation between each other (r=0.73; p<0.001) as well as with hHSP60 (cHSP60: r=0.74; p<0.001; CMV: r=0.80; p<0.001). Macrophage infiltration correlated with cHSP60 (r=0.78; r<0.001), CMV (r=0.78; r<0.001) and hHSP60 (r=0.56; r=0.007). Of note, the frequency of cHSP60, CMV and CD68 signaling was increased more than 5-fold in prosthetic valves compared to native valves (p=0.017, p=0.002 and p=0.005). ??In summary, valvular infections of Chlamydia pneumoniaeand of cytomegalovirus are frequently seen in degenerated aortic valves, irrespective of native or prosthetic origin. Colocalization of both HSP60 homologues and cytomegalovirus within macrophages in valvular fibrosa points to regional stressor effects that might be at least partly attributable to chronic persistent pathogen burden and molecular mimicry. Aktuelle Evidenzen legen eine kausale Beziehung zwischen inflammatorischen wie auch infektiösen Pathogenesemechanismen und der Degeneration von Herzklappen nahe. Basierend auf dem Konzept von chronischen Chlamydia pneumoniae- und Zytomegalie-Virus (CMV)-Infektionen und zusätzlichen Stressoren, die auf die valvuläre Mikroökologie einwirken, untersucht die vorliegende Studie die Präsenz des Erreger-spezifischen chlamydialen Hitzeschockproteins (cHSP) 60, von CMV, von Makrophagen und des humanen Homologs hHSP60. ??Serielle Schnitte hochgradig degenerativ veränderter nativer Aortenklappen (n=16) und Aortenklappenbioprothesen (n=6) wurden immunhistochemisch auf die Präsenz dieser Determinanten untersucht. Degenerativ veränderte Aortenklappen zeigten in 41% eine Prävalenz von Chlamydia pneumoniaeund in 73% eine von CMV, während immunreaktives hHSP60 in 64% und CD68 in 86% aller Fälle nachweisbar waren. Chlamydiales HSP60, CMV und hHSP60 waren bevorzugt in der valvulären Fibrosa präsent; CMV zeigte zusätzlich eine zweite Prädilektionsstelle am ventrikulären luminalen Rand. Beide Erreger wiesen eine positive Korrelation sowohl untereinander (0,73; p<0,001) als auch mit hHSP60 auf (cHSP60: r=0,74; p<0,001; CMV: r=0,08; p<0,001). Die Makrophagen-Infiltration korrelierte mit cHSP60 (r=0,78; r<0,001), CMV (r=0,72; p<0,001) und hHSP60 (r=0,56; r=0,007). Bemerkenswerterweise war die Frequenz von cHSP60-, CMV- und CD68-Signalen in degenerierten prothetischen Aortenklappen signifikant höher als in nativen Klappen (p=0,017, p=0,002 und p=0,005). ??Zusammenfassend sind valvuläre Infektionen mit Chlamydia pneumoniaeund Zytomegalie-Virus in degenerativen Aortenklappen häufig nachweisbar, unabhängig von nativer oder prothetischer Herkunft der Klappen. Die Kolokalisation mit Makrophagen, die beide HSP60-Homologe und Zytomegalie-Virus in der valvulären Fibrosa ausweisen, legen regionale Stressor-Effekte nahe, die durch eine chronisch persistierende Erregerlast und molekulares Mimikry zumindest partiell bedingt sein könnten.

A 45 year old male suffered from typical exercise-induced dyspnoea and angina. Crohn‘s disease treated with glucocorticoids was present for 18 years. Coronary angiography revealed small left anterior descending and right coronary arteries without reference to coronary artery disease, while the main stem and circumflex artery were severely dilated due to a fistula (diameter 5.5 mm) into the coronary sinus with a left/right shunt amounting to 35%. Haemodynamics, significant risk of endocarditis with chronic inflammatory bowel disease and obligatory glucocorticoid treatment were indications for fistula closure. As an alternative to surgical correction, the coronary fistula was totally occluded by antegrade micro-coil embolization. The present report offers a review on differential therapeutic considerations and specific treatment options including novel interventional modalities for coronary fistulas. Ein 45-jähriger Patient entwickelte typische belastungsinduzierte Dyspnoe und Angina pectoris. Seit 18 Jahren bestand ein M. Crohn mit Glukokortikoid-Medikation. Koronarangiographisch stellten sich Ramus interventricularis anterior und rechte Kranzarterie klein und ohne Hinweis auf eine koronare Herzerkrankung dar, während Hauptstamm und Ramus circumflexus aufgrund einer Fistelbildung (Diameter 5,5 mm) in den Sinus coronarius massiv dilatiert waren mit einem Links/Rechts-Shunt von 35%. Hämodynamik, erhöhtes Endokarditisrisiko bei chronisch-entzündlicher Darmerkrankung und Glukokortikoid-Pflichtigkeit waren Indikation für den Fistelverschluss. Als Alternative zur chirurgischen Korrektur wurde die Koronarfistel mittels antegrader Embolisierung mit Micro-Coils komplett verschlossen. Die vorliegende Arbeit gibt einen Überblick über differentialtherapeutische Abwägungen und spezifische Behandlungsoptionen einschließlich neuer interventioneller Verfahren bei koronaren Fistelbildungen.

Background:Focussing on regional cerebral hypoperfusion during hemodynamically stable, but borderline hypotensive, sustained ventricular tachycardia (VT) experimental studies show (1) a reduction of cerebral blood flow (CBF) during tachyarrhythmias in contrast to the concept of CBF autoregulation, (2) a mediation of hypoperfusion by neuronal and humoral mechanisms, and (3) an involvment of microcirculation due to an ischemic stress response of the cerebral tissue. The clinical relevance of these observations remains still unclear. Case reports:Two patients with coronary artery disease, left ventricular dysfunction and sustained monomorphic VT underwent electrophysiological study. VT was induced and the tracer 99mTc-HMPAO was injected after 3 minutes of ongoing VT. Regional CBF during this life threatening arrhythmia was determined with brain SPECT. A scanning protocol was performed after termination of VT. The measurements were repeated at baseline during normofrequent sinus rhythm (SR) one week later. CBF during SR was significantly reduced in the temporal lobe in comparison to the conditions during stable VT, particularly in the left hippocampus. Conclusion:The reduction of hippocampal CBF due to cerebrovascular vasoconstriction and neuronal reflex mechanism previously observed in experiments during stable, sustained VT can be confirmed in a clinical scenario by high resolution 99mTc-HMPAO brain SPECT. This supports the hypothesis that repetitive stable VT can play a role in the pathophysiology of cerebrovascular insufficiency. Further clinical studies are needed to analyze the impact of tachyarrhythmias on cognitive and mnemic function.

OBJECTIVES

Ecological investigations at four streams in Saxony-Anhalt have shown that there are considerable differences between the self-purification power of upland and lowland streams. This result is reflected in chemistry and in microbiology. The structure of the bottom substrate mainly influences the degree of self-purification in connection with rate of flow and flow velocity. The results and differences are demonstrated using the example of Katzsohlbach in the landscape unit “Mittel- and Unterharz” and the stream Olbe in the landscape unit “Magdeburger Börde”.

xenon, CO using Doppler echocardiography or impedance cardiography. Mean and individual CBF in controls remained unchanged when a CO increase of 28% induced by volume overload was observed. In PM patients a mean CO increase of 38% induced by an increase of basic pacing rate caused different effects on CBF. CBF increased or decreased by about 10% or remained constant. In summary, the data suggest an impairment of cerebrovascular function in those patients with concomittant CBF changes due to CO alterations (15/23?65%). Thus, the analysis of brain perfusion in PM patients with unspecific neurological symptoms is possibly a new diagnostic feature in the future. It can be discussed whether or not indication and optimizing of pacemaker therapy has to be additionally analyzed by determination of endorgan perfusion. Xenon, HZV mittels Dopplerechokardiographie oder Impedanzkardiographie vor und nach einer Veränderung des HZV bestimmt. Bei Kontrollpersonen erfolgte durch Volumenbelastung ein Anstieg des HZV um 28%; CBF blieb im Mittel und individuell unverändert. Bei PM-Patienten lassen sich durch Erhöhung der Basisstimulation bei HZV-Anstiegen um 38% unterschiedliche Auswirkungen auf CBF beobachten. Es werden Zu- und Abnahmen um ca. 10% sowie physiologische Reaktionsmuster dokumentiert. Insgesamt weisen die Befunde auf eine Störung der zerebrovaskulären Funktion bei den Patienten hin, bei denen HZV-Veränderungen zu einer CBF-Änderung führen (15/23?65%). Die Analyse der Hirnperfusion könnte daher bei PM-Patienten mit unspezifischen neurologischen Symptomen in Zukunft eine diagnostische Erweiterung darstellen. Indikationsstellungen und Optimierungen einer Schrittmachertherapie könnten unter Umständen durch Bestimmung der Endorganperfusion erweitert werden.

Objective: To evaluate the feasibility of flow determinations by contrast replenishment using harmonic power Doppler imaging (H‐PDI). Background: The application of indicator dilution principles on contrast echocardiography is limited by numerous methodical problems. Recently, a new method was introduced that relies on ultrasound‐mediated microbubble destruction and evaluation of the contrast replenishment. Methods: Definity, a perfluorocarbon‐derived contrast agent under development, was continuously infused into a steady flow phantom and H‐PDI registrations were performed within a silicone tube (d = 8 mm). Replenishment interval between destruction and imaging frame was varied from 0.04–2 seconds. Nonlinear curve fitting was performed using an exponential mathematical model. Results: Strong linear correlation between contrast dose and maximum signal intensity as well as between flow and the slope variable β of the replenishment curve was found for all settings (r > 0.96). Maximum signal intensity and contrast replenishment rate were found to be a function of emission power and were significantly influenced by depth and focus position. Conclusion: The feasibility of flow assessment using replenishment curves obtained by H‐PDI was demonstrated. However, in experimental conditions, flow analysis was severely influenced by ultrasound system settings and imaging conditions such as emission power, sound field geometry, and investigation depth. For a clinical use of this promising approach, algorithms that take specific system settings and imaging conditions into account have to be found. Imaging modalities that enable a most homogeneous scan field are best suited for the assessment of contrast replenishment.

133: xenon, CO using Doppler echocardiography or impedance cardiography. Mean and individual CBF in controls remained unchanged when a CO increase of 28% induced by volume overload was observed. In PM patients a mean CO increase of 38% induced by an increase of basic pacing rate caused different effects on CBF. CBF increased or decreased by about 10% or remained constant. In summary, the data suggest an impairment of cerebrovascular function in those patients with concomittant CBF changes due to CO alterations (15/23≅65%). Thus, the analysis of brain perfusion in PM patients with unspecific neurological symptoms is possibly a new diagnostic feature in the future. It can be discussed whether or not indication and optimizing of pacemaker therapy has to be additionally analyzed by determination of endorgan perfusion.

Seit der Beobachtung, dass mittels Schrittmacherstimulation das Auftreten von vagalvermitteltem Vorhofflimmern verhindert werden kann, werden variantenreiche Versuche unternommen, die Elektrotherapie in der Vorhofflimmerrezidivprophylaxe zu etablieren. Sowohl die multilokuläre atriale Stimulation, wie z. B. die biatriale oder bifokale rechtsatriale Stimulation als auch die septale Stimulation versuchen primär, das elektrophysiologische Substrat, z. B. eine intra- oder interatriale Leitungsstörung, zu beeinflussen. Präventive Stimulationsalgorithmen dagegen zielen darauf ab, atriale Extrasystolen oder Salven, die bekanntermassen Vorhofflimmern auslösen können, zu unterdrücken. Beispielhaft für die Arbeitsweise präventiver Algorithmen können die vier Stimulationsstrategien der “AFtherapy”-Studie gelten. “Pace-Conditioning”: Dieser Algorithmus stabilisiert die Stimulationsfrequenz variabel oberhalb des intrinsischen Sinusrhythmus. Ziel ist es, in über 95% der atrialen Ereignisse eine Vorhofstimulation durchzuführen. Suppression von Vorhofextrasystolen: Bei Wahrnehmung einer atrialen Extrasystole wird die Stimulationsrequenz um 15 min−1über einen variablen Zeitraum angehoben, um den extrasystolischen Fokus zu unterdrücken. Extrasystolen-Antwort:Die Wahrnehmung einer Extrasystole induziert eine Verkürzung des Auslöseintervalls der anschließenden beiden Zyklen, um die arrhythmogene postextrasystolische Pause zu vermeiden. Frequenzkontrolle in der Nachbelastungsphase:Dieser Algorithmus adaptiert die Stimulationsfrequenz der Erholungsphase an die Dauer und das Ausmaß der Belastung, die der Patient absolviert hat. Es soll damit ein zu rascher Frequenzabfall in der Erholungsphase vermieden werden. Diese wie auch andere präventive Stimulationsalgorithmen befinden sich momentan in der klinische Erprobungsphase, um den Stellenwert der Schrittmachertherapie in der Rezidivprophylaxe des Vorhofflimmerns zu klären. Since the observation that antibradycardia pacing may prevent vagal-mediated parosysmal atrial fibrillation, several approaches have been undertaken to establish pace-prevention of atrial fibrillation as a therapeutic option in such patients. Multisite pacing strategies like biatrial, bifocal right atrial or septal pacing are in first line so-called substrate-modulators of atrial fibrillation that try to compensate for inter- and intraatrial conduction disturbances. Preventive pacing algorithms, which can be used with a conventional atrial lead position, are designed to suppress premature atrial contractions and salvos as a known trigger of atrial fibrillation. Pace conditioning:This algorithm adjusts the rate just above the intrinsic sinus rate with the aim to overdrive and pace the atrium for at least 95% of the time. Premature atrial contraction suppression:When a spontaneous atrial event is classified as a premature atrial contraction, the pacing rate is increased to 15 min-1 above the physiological rate and kept stable for a certain period. Post-premature atrial contraction response:This algorithm is designed to prevent arrhythmogenic pauses after premature atrial contractions by controlling the atrial rate only in the two beats after each premature atrial contraction. Post-exercise response:The post-exercise pacing rate is adjusted to both the level and the duration of exercise in order to prevent too step of a rate drop at the onset of the recovery phase. These four preventive pacing algorithms are currently investigated in the AFtherapystudy. The results of this and other prospective pacing studies will not only clarify the relevance and effectiveness of pacing for prevention of atrial fibrillation but will also enlarge our knowledge about the induction mechanisms of atrial fibrillation in patients.

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 implantion (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. Die Mehrzahl der Neuimplantationen aller Kardioverter-/Defibrillator-Systeme erfolgt heute ohne Thorakotomie mit endovenösen Elektrodensystemen. Für epikardiale Systeme wurde die Langzeitstabilität für die Defibrillationsschwelle (DFT) eingehend untersucht. Für den Verlauf der DFT bei transvenöser Implantationstechnik liegen bisher widerspüchliche Ergebnisse vor. Ziel der vorliegenden Untersuchung war es, die akute und chronische Defibrillationseffektivität bei Patienten mit implantierbarem Defibrillator und „Active-Can“-Elektrodenkonfiguration im Langzeitverlauf über 12 Monate zu vergleichen. Die bei Implantation des Defibrillators mit einem endokardialen Elektrodensystem erreichte Defibrillationseffektivität wurde postoperativ vor Entlassung aus der Klinik, nach 3, 6 und 12 Monaten erneut bestimmt. Das Patientenkollektiv bestand aus 8 Frauen und 38 Männern mit einem mittleren Alter von 57,2±13,2 (22–76) Jahren. Die mittlere linksventrikuläre Ejektionsfraktion betrug 43,8±16,9 (15–82)%. Der überwiegende Anteil der Patienten hatte eine koronare Herzerkrankung (67,4 %); acht Patienten hatten eine dilatative Kardiomyopathie.¶ ??Bei 39 Patienten wurde die DFT zu den geplanten fünf Testzeitpunkten bestimmt. Die mittlere DFT bei Implantation betrug 9,2±5,9 Joule (J), postoperativ vor Entlassung 7,6±4,8 J, bei der 3-Monats-Kontrolle 8,6±5,7 J, nach 6 Monaten 8,1±6,0 J und nach 12 Monaten 8,6±5,8 J. Die DFT vor Entlassung war signifikant niedriger als bei Implantation (7,6 J versus 9,2 J; p=0,021). Zwischen der DFT bei Implantation und der DFT bei der 3-Monats-Kontrolle und im weiteren Verlauf bestand kein signifikanter Unterschied (9,23 versus 8,56; p=0,291). In der Multivarianz-Analyse zeigte sich für die DFT eine zeitliche Abhängigkeit, die durch den signifikanten Abfall der DFT zum Zeitpunkt der Entlassung bedingt ist. Diese Verringerung der DFT hatte keinen Einfluss auf die Stabilität der Defibrillationsschwelle.¶ ??Bei ICDs mit einem „Active-Can“-Elektrodensystem erlaubt somit die intraoperativ bestimmte Defibrillationsschwelle eine gute Vorhersage der chronischen Defibrillationseffektivität.

Atrial fibrillation (AF) is a frequent and costly health care problem representing the most common arrhythmia resulting in hospital admission. Total mortality and cardiovascular mortality are significantly increased in patients with AF compared to controls. In addition to symptoms of palpitations, patients with AF have an increased risk of stroke and may also develop decreased exercise tolerance and left ventricular dysfunction. All of these problems may be reversed with restoration and maintenance of sinus rhythm. External electrical cardioversion has been a remarkably effective and safe method for termination of this arrhythmia. Originally described by Lown et al. in 1963, it has been a well accepted mode of acute therapy. However, this technique requires general anesthesia or heavy sedation. Internal atrial defibrillation has been evaluated as an alternative approach to the external technique for over 2 decades. Recent studies have shown that low-energy internal atrial defibrillation using biphasic shocks is an effective and safe means in restoring sinus rhythm in patients with AF and should be considered especially in patients in whom external cardioversion attempts have failed. Implantable Atrial Defibrillator:Recently, a stand alone IAD, the Metrix™System (models 3000 and 3020), has entered clinical investigation. Atrial defibrillation is accomplished by a shock delivered between electrodes in the right atrium and the coronary sinus. The right atrium lead has an active fixation in the right atrium. The coronary sinus lead has a natural spiral configuration for retention in the coronary sinus, and can be straightened with a stylet. Both leads are 7 French in diameter and the defibrillation coils are each 6 cm in length. The electrodes may be placed using separate leads, or very soon by using a single bipolar lead. A separate bipolar right ventricular lead is used for R wave synchronization and post shock pacing. The Metix™defibrillator can be used to induce AF by using R wave synchronous shocks and can store intracardiac electrograms (EGMs) for up to 2 minutes from the most recent 6 AF episodes. The device can be programmed into one of the following operating modes: fully automatic, patient activated, monitor mode, bradycardia pacing only, and off. As AF is not life-threatening, in the automatic mode the device is only intermittently active in detecting and treating AF, and this “sleep wake-up” cycle interval is programmable. The device employs extensive processing both for detection and R wave synchronization. In April 1996, the phase I Metrix™multicenter clinical trial was started. As of May 1997, a total of 51 Metrix™systems had been implanted as part of the phase I multicenter clinical trial. Preliminary data suggest that both defibrillation thresholds and electrograms are stable over time (implant to 3 months). Detection accuracy has been excellent (100% specificity, 92.3% sensitivity) and there have been no errors of R wave selection for synchronization. No proarrhythmias have resulted from over 3700 shocks delivered. The device is effective in electrically converting 96% of the spontaneous episodes of AF. In 27% of episodes several shocks were required because of early recurrence of AF. In 5 patients, the atrial defibrillator was removed: 2 infections, 1 cardiac tamponade, 1 permanent loss of telemetry, 1 patient required His-Bundle ablation because of frequent episodes of drug refractory AF with rapid ventricular response. Initial clinical experience under controlled conditions with the Metrix™system suggests that the implantable atrial defibrillator 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. Combined Atrioventricular Defibrillator:Recently, a new dual-chamber defibrillator, the 7250 Jewel®AF AMD, has entered clinical evaluation. Concern has been raised whether or not a stand alone implantable atrial defibrillator is safe enough or should provide ventricular backup defibrillation in the rare case of shock induced ventricular proarrhythmia. The availability of a dual-chamber defibrillator has reactivated the discussion about the safety of a stand alone implantable atrial defibrillator. The most important new features of the 7250 Jewel®AF AMD system include dual-chamber pacing, a new dual-chamber detection criterion for rejection of supraventricular tachycardias, detection and treatment modalities of atrial arrhythmias, prevention strategies for atrial arrhythmias. Initial clinical experience with the 7250 Jewel®AF AMD device that combines both detection and treatment in the atrium as well as in the ventricle indicates a significant improvement in the management of patients with both supraventricular and ventricular tachyarrhythmias. Die transthorakale Defibrillation von Vorhofflimmern, die 1963 von Lown et al. beschrieben wurde, ist eine etablierte und effektive Methode zur Akuttherapie. Nachteile der externen Elektroschockapplikation sind die Notwendigkeit einer Kurznarkose und der Bedarf einer vergleichsweise hohen Energie von bis zu 360 J. Als alternative Behandlungsmaßnahme kommt die intraatriale Kardioversion in Betracht. Neuere Untersuchungen haben gezeigt, daß die intraatriale Kardioversion von Vorhofflimmern ein sicheres und wirksames Therapieverfahren darstellt, das insbesondere nach erfolgloser externer Defibrillation erwogen werden sollte. Der niedrigste Energiebedarf ist mit biphasischen Schockformen und einer Elektrodenkonfiguration zu erreichen, bei der eine Elektrode im Sinus coronarius und eine zweite Elektrode im rechten Vorhof plaziert wird. Die guten Ergebnisse der intraatrialen Kardioversion von Vorhofflimmern haben die konsequente Weiterentwicklung eines implantierbaren Elektrosystems zur Therapie von Vorhofflimmern ermöglicht. Ausgewählte Patienten mit symptomatischen, medikamentös therapierefraktären, lang anhaltenden Episoden von Vorhofflimmern, die mit einer Häufigkeit zwischen einmal pro Woche und bis zu einmal alle drei Monate auftreten, stellen mögliche Kandidaten für ein atriales Defibrillator stellen vor allem das potentielle Risiko der Induktion einer ventrikulären Proarrhythmie und die subjektive Mißempfindung bei rezidivierenden Schockentladungen die Grundlage für kontroverse Diskussionen dar. Der kombinierte atrioventrikulare Defibrillator verfügt nicht nur über eine Therapieoption im Ventrikel, sondern auch im Vorhof, so daß dieses elektrotherapeutische Verfahren insbesondere für Patienten mit malignen Herzrhythmusstörungen und zusätzlichen Vorhofrhythmusstörungen in Betracht kommt.

Atrial flutter can be understood as atrial tachycardia due to a single intraatrial macroreentrant circuit that is determined by fixed or functional bounderies. In various types of atrial flutter, radiofrequency ablation became an established curative therapy. During the course of an ablation procedure, initially, the reentrant circuit has to be determined, e.g. by activation and entrainment mapping. Subsequently, the bounderies have to be identified. By connecting two appropriate boundaries with a linear lesion, the intraatrial reentrant circuit can be inhibited. Finally, it should be proven that the linear lesion results in a complete line of conduction block. Doing so, the acute and long-term results of atrial flutter ablation are comparable to those of other supraventricular tachycardias. Bei typischem Vorhofflattern handelt es sich um eine intraatriale Tachykardie mit singulärem Makroreentry um die Trikuspidalklappe. Verantwortlich für den stabilen Reentrykreis sind anatomische Strukturen mit leitungsblockierender Wirkung. Bei der Katheterablation wird durch eine lineare Läsion zweier gegenüberliegender Barrieren der kreisförmige Wiedereintritt unterbunden. Etabliert ist die Ablation zwischen V. cava inferior und Trikuspidalklappe. Aufgrund einer geringeren Myokarddicke und einer relativ kürzeren Wegstrecke wird alternativ die lineare Läsion zwischen Eustachischer Klappe und Trikuspidalklappe empfohlen. Um eine lineare Läsion zu erzeugen, werden zwischen beiden Barrieren konsekutiv Radiofrequenzimpulse abgegeben. Durch Verwendung langer Führungsschleusen, anatomisch angepaßter Ablationskatheter, größerer oder gekühlter Ablationselektroden kann die Produktion der notwendigen transmuralen Läsionen erleichtert werden. Insgesamt wird heute eine akute Erfolgsrate von über 90% erreicht. Für den Langzeiterfolg ist die Dokumentation der Kontinuität der linearen Läsionen notwendig. Dies erfolgt durch den Nachweis von Doppelpotentialen an der Ablationslinie und durch endokardiales Aktivierungsmapping im Bereich der Trikuspidalklappe. Neuere dreidimensionale Mapping-Systeme können bei der Dokumentation eines kompletten Leitungsblockes bzw. zur Lokalisation persistierender Erregungsübertritte hilfreich sein.

Die Radiofrequenzablation ist die Therapie der Wahl in der Behandlung von AV-Knoten-Reentrytachykardien. Elektrophysiologische Untersuchungen bei 623 Patienten zeigte acht Mechanismen der Katheterablation: Die Ablation des schnelle (I.) oder des langsamen (II.), die Modifikation des schnelle (III.) oder des langsamen Leitungsweges (IV.), die Modifikation beider Leitungswege (V.), die Ablation des schnellen mit der Modifikation des langsamen (VI.), die Ablation des langsamen mit der Modifikation des schnelle (VII.) sowie die Ablation beider AV-Knotenleitungsbahnen (VIII.). Diagnostische Kriterien dieser acht Mechanismen einer Katheterablation bei AV-Knoten-Reentrytachykardie werden beschrieben. Im Verlauf zeigte sich eine geringere Rezidivrate bei Patienten mit vollständiger Ablation einer AV-Knotenleitungsbahn (0–2%) im Vergleich zu den Patienten nach Modifikation eines Leitungsweges (8–12%). Die Alteration beider Leitungsbahnen hat ein höheres Risiko eines totalen AV-Blocks, der bei 7 Patienten (1.1%) auftrat. Die genaue Untersuchung des Mechanismus der Katheterablation einer AV-Knoten-Reentrytachykardie wird empfohlen zur Bestimmung des Risikos eines Patienten, ein Rezidiv im Verlauf oder einen totalen AV-Block während eines weiteren ablativen Eingriffs zu erleiden. Radiofrequency catheter ablation is the treatment of choice in atrioventricular nodal reentrant tachycardia. Electrophysiologic investigations in 623 patients revealed eight mechanisms of tachycardia ablation: Ablation of fast (I) or slow(II), modification of fast (III) or slow AV nodal pathways (IV), modification of both pathways (V), ablation of fast and modification of slow (VI), ablation of slow and modification of fast pathways (VII) and ablation of both pathways (VIII). The criteria of diagnosis of these eight mechanisms of tachycardia ablation are described. Follow-up showed fewer relapses in patients with ablation (0–2%) in comparison to patients with modification of a single AV nodal pathway (8–12%). Alteration of both pathways includes an increasing risk of total AV nodal block, which occured in 7 patients (1.1%). Detailed analysis of the mechanism of catheter ablation is recommended in all patients after radiofrequency current delivery for AV nodal reentrant tachycardia to estimate the risk of relapsing during follow-up or development of total AV block in the particular patient in case of a further ablation procedure.

Background: Harmonic power Doppler imaging (H‐PDI) has been introduced into the field of contrast echocardiography as a contrast‐specific imaging modality. However, there has been considerable skepticism as to whether H‐PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H‐PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether micro‐bubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow. Methods and Results: A strong positive correlation was found between the H‐PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r= 0.968, P < 0.001). Time‐intensity curves for H‐PDI of air‐filled microbubbles were compared with time‐concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r> 0.98, P < 0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green. Conclusions: We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H‐PDI technology allows a reliable assessment of time‐concentration curves of air‐filled microbubbles up to the onset of acoustic shadowing. (ECHOCARDIOGRAPHY, Volume 17, January 2000)

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.

In patients with atrial fibrillation (AF), the restoration and maintenance of sinus rhythm is the primary therapeutic goal. Once sinus rhythm is maintained, physiological rate control is restored, and left ventricular ejection fraction, cardiac output, and exercise capacity are increased. This improved cardiovascular performance thereby enhances the patient's ability to perform the functions of normal daily life. The primary intervention for maintaining sinus rhythm after restoration is the use of anti-arrhythmic agents. Although physicians mostly use class 1A anti-arrhythmic drugs, these oral agents only maintain sinus rhythm in a limited number of cases and are accompanied by considerable side effects. Therefore, more effective tools are needed. Effective treatment for AF is based on the above objective criteria, but subjective criteria such as the quality of life are growing in importance. To address these quality-of-life issues, we have initiated a prospective study in which patients are assigned to one of two groups: those with paroxysmal AF who are candidates for permanent implantable atrial defibrillators and those with chronic or paroxysmal AF who are not candidates for atrial defibrillators. Specifically designed questionnaires and various standardized and validated instruments are used to measure quality of life. The questionnaires cover social demographic data, including age, education, occupation level, driving behavior, return to work, and sexual activity. Quality of life is a multidimensional construct, and thus its definition must consider the many factors mentioned above. In the final analysis, therefore, both objective and subjective criteria are necessary to define appropriate treatment of AF.

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® and EnSite®, may further enhance the accuracy of conventional mapping techniques.

Documentation of atrial signals in stored endocardial electrograms of modern implantable cardioverter-defibrillators (ICD) is a useful tool to classify the underlying arrhythmia leading to device therapy. Newest generations of ICD provide near- and far-field electrograms derived between various endocardial electrodes. The aim of this prospective study was to assess the quality and long-term stability of atrial signals in different far-field configurations including the active can housing. Methods and Results: A total of 300 real-time endocardial electrogram recordings in 60 consecutive patients with a modern ICD in subpectoral position were analysed at the time of implant, pre-hospital discharge, 1, 3 and 12 months<%0> follow-up. Four different configurations were evaluated: right ventricular coil to can housing, can housing to pace/ sense ring, right ventricular coil to pace/sense tip, and pace/ sense tip to pace/sense ring. The best visibility of p-waves at an ECG-resolution of 0.5 mV/mm was seen in the can to coil configuration (77% of the patients). In the can to pace/sense ring electrogram p-waves could be observed in 58% of the patients. No p-waves were visible to pace/sense tip to pace/ sense ring. At a resolution of 1.0 mV/mm p-waves were only visible in 10% of all patients exclusively in the can housing to right ventricular coil configuration. The results were stable (100% of the patients) over a follow-up of one year. Conclusions: Endocardial far-field electrograms, derived from the can housing and the right ventricular coil provide a p-wave visibility in 77% of the patients and demonstrate a long-term stability over at least one year, provided that the ECG-resolution is set at 0.5 mV/mm. Since the electrogram resolution of stored electrograms depends on the EGM-range, and the ECG-resolution at an EGM-range of 15 mV would be 1 mV/mm, the EGM-range is recommended to be programmed to 7.5 mV to ensure an ECG-resolution of at least 0,5 mV/mm for stored electrograms.

Background: It has been shown that cardioversion of atrial fibrillation may result in left atrial chamber and appendage dysfunction and cause new thrombi in the left atrium. The aim of this prospective study was to investigate right atrial appendage function and assess the incidence of new right atrial thrombi after electrical cardioversion. Methods: Transthoracic echocardiography was performed in 25 patients 4 h before and at 24 h and 7 days after electrical cardioversion to determine right and left atrial mechanical function (internal atrial defibrillation, n = 16; external electrical cardioversion, n = 9), as assessed by peak A wave velocities derived from the transtricuspid and transmitral velocity profiles. In addition, transesophageal echocardiography was performed 4 h before and 24 h after cardioversion to evaluate postcardioversion thrombus formation in the right and left atrial chambers and to assess right and left atrial appendage function. The degree of spontaneous echo contrast was noted, and peak emptying velocities of the appendages were measured before and after cardioversion.Results: Peak emptying velocities of both the right atrial appendage (mean ± SD, 0.23 ± 0.1 vs 032 ± 0.11 m/sec; P = 0.02) and the left atrial appendage (0.3 ± 0.15 vs 0.4 ± 0.15 m/sec; P = 0.01) were significantly lower 24 h after cardioversion compared with 4 h before cardioversion, respectively. The degree of spontaneous echo contrast increased in the left atrium after cardioversion from 1.0 ± 1.2 to 1.9 ± 2.1 (P = 0.02), and in the right atrium, it increased from 0.8 ± 1.1 io 1.2 ± 1.1 (P = 0.1) after cardioversion. Peak A wave transtricuspid velocity increased from 0.26 ± 0.05 m/sec at 24 h to 0.38 ± 0.06 m/sec (P = 0.001) after 7 days; respective values for transmitral peak A wave velocity were 0.39 ± 0.15 and 0.54 ± 0.16 m/sec (P = 0.009). No thrombi were found in either the right or left atrium before cardioversion. In two patients, new thrombi in the right atrium were detected 24 h after internal atrial defibrillation. Thrombi were located at the superior rim of the fossa ovalis in both patients with patent foramen ovale. Another patient had developed a thrombus in the left atrial appendage.Conclusions: Electrical cardioversion may not only cause left atrial chamber and appendage dysfunction and left atrial thrombi but also lead to depressed right atrial appendage function and the generation of new thrombi in the body of the right atrium.