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Background Oral anticoagulation (OAC) reduces thromboembolic events and mortality in patients with atrial fibrillation (AF). Anticoagulation rates have substantially increased over recent years. Still, a number of patients are not receiving guideline recommended OAC. Purpose To investigate clinical factors and reasoning associated with non-prescription of OAC in a current German registry. Methods The German AFNET 2 registry is a prospective multi-center registry on atrial fibrillation comprising a total of 3491 patients from all levels of medical care (general practitioners, cardiologists, hospitals; enrolment 5/2014 to 3/2016). The registry was conducted in collaboration with the EORP program of the ESC. Here, only patients with non-valvular AF and at least two clinical risk factors for stroke (using CHA2DS2-VASc score) were considered. Results The study population consisted of 2856 patients, 58.4% male, mean age 75.5±7.8 years, mean CHA2DS2-VASc score 4.1±1.5, mean HAS-BLED score 1.8±1.0. Overall, the rate of OAC was 94.3%. 54% of these received Vitamin K antagonists (VKA) and 46% NOAC. 2.3% received antiplatelets only. Patients newly initiated on OAC mostly received a NOAC (82.5% of patients). Anticoagulation rate was lower in elderly patients (age Conclusions Within registries, the guideline recommended use of OAC is very high in Germany indicating high guideline adherence by prescribing physicians. However, use of antiplatelet therapy was associated with non-prescription of OAC. In addition, a high HAS-BLED score appears to be a relevant argument for withholding proven OAC for stroke prevention in patients with AF. Acknowledgement/Funding BMS Germany; DZHK

The HAWAI registry evaluated the role of heart rate variability in predicting the occurrence of ventricular tachycardia and fibrillation (VT/VF) and sinus tachycardia in patients with an implantable cardioverter-defibrillator (45 patients with 155 RR recordings). A significant decrease of the mean value of all RR intervals (MeanNN) was observed in the period starting 20 and 40 min prior to VT/VF and sinus tachycardia, respectively. The standard deviation of RR intervals (SDNN) and the power at low frequency (LF) were the only parameters with significant changes prior to VT/VF. For sinus tachycardia, the root mean square of successive differences of all successive RR intervals (r-MSSD) and the power at low and high frequency (HF) decreased, whereas SDNN and the power at very low frequency increased. Comparison of RR recordings preceding VT/VF and sinus tachycardia revealed significant differences of the MeanNN, SDNN, r-MSSD, LF and HF. Based on a classification and regression tree analysis, MeanNN, SDNN and r-MSSD showed a sensitivity of 94.4% and a specificity of 50.6% as predictors of VT/VF. Our results suggest that the temporal changes in heart rate before an arrhythmic event can be used to predict the occurrence of VT/VF. These parameters may be used to optimize pacing therapies designed to prevent VT/VF recurrences as well as for improving device-based discriminators for VT/VF and sinus tachycardia.

Die damalige Deutsche Gesellschaft fur Kreislaufforschung, heute Deutsche Gesellschaft fur Kardiologie – Herz- und Kreislaufforschung, wurde 1927 von Bruno Kisch und Arthur Weber gegrundet. Lange Zeit dominierten die „Theoretiker“ (Physiologen, Pathologen, Pharmakologen) die Gesellschaft. Zu Beginn der 1970er-Jahre forderten die klinisch tatigen Mitglieder der Gesellschaft fur sich einen groseren Einfluss in der Gesellschaft. Es bestand die Gefahr der Grundung einer eigenen Gesellschaft. In dieser Situation entstand 1971 wahrend der 37. Mitgliederversammlung der Deutschen Gesellschaft aus dem „Ausschuss fur Klinische Kommission“ die Kommission fur Klinische Kardiologie (KKK). Es war die Zeit der Entstehung neuer Herzkathetertechniken und neuer Herzkatheterlabore. Die KKK initiierte und organisierte ab 1974 die klinisch orientierten Herbsttagungen der Gesellschaft, griff Fragen der klinischen Kardiologie auf und verfasste und publizierte Leitlinien, damals zuerst Richtlinien genannt. Die erste erschien 1983 und damit vor den ersten ACC/AHA Clinical Practice Guidelines. Heute werden die Leitlinien durch internationale Leitlinien der European Society of Cardiology, angepasst an deutsche Verhaltnisse, erganzt und seit 1996 auf der Internetseite der Gesellschaft publiziert. Auserdem wurde 1982 der erste von nachfolgend 25 (2010) Berichten uber Struktur und Leistungszahlen der Herzkatheterlabore in der Bundesrepublik Deutschland (heute Herzbericht) publiziert.

Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed in September 2015 to promote discussion and research about AF screening as a strategy to reduce stroke and death and to provide advocacy for implementation of country-specific AF screening programs. During 2016, 60 expert members of AF-SCREEN, including physicians, nurses, allied health professionals, health economists, and patient advocates, were invited to prepare sections of a draft document. In August 2016, 51 members met in Rome to discuss the draft document and consider the key points arising from it using a Delphi process. These key points emphasize that screen-detected AF found at a single timepoint or by intermittent ECG recordings over 2 weeks is not a benign condition and, with additional stroke factors, carries sufficient risk of stroke to justify consideration of anticoagulation. With regard to the methods of mass screening, handheld ECG devices have the advantage of providing a verifiable ECG trace that guidelines require for AF diagnosis and would therefore be preferred as screening tools. Certain patient groups, such as those with recent embolic stroke of uncertain source (ESUS), require more intensive monitoring for AF. Settings for screening include various venues in both the community and the clinic, but they must be linked to a pathway for appropriate diagnosis and management for screening to be effective. It is recognized that health resources vary widely between countries and health systems, so the setting for AF screening should be both country- and health system-specific. Based on current knowledge, this white paper provides a strong case for AF screening now while recognizing that large randomized outcomes studies would be helpful to strengthen the evidence base.

Die Deutsche Gesellschaft fur Kardiologie (DGK) legt hiermit ein Curriculum zur Erlangung einer Zusatzqualifikation „Spezielle Rhythmologie“ vor, um besondere Kenntnisse, Erfahrungen und Fertigkeiten anzuerkennen, das sich an die Anforderungen der European Heart Rhythm Association (EHRA) anlehnt. Neben dem Erwerb der Zusatzqualifikation „Spezielle Rhythmologie“ (24 Monate) konnen auch die Blocke „Invasive Elektrophysiologie“ bzw. „Aktive Herzrhythmusimplantate“ separat erworben werden (jeweils 15 Monate). Die Erteilung des Zertifikats setzt die Anerkennung als „Arzt fur Innere Medizin und Kardiologie“ voraus. Beschrieben werden Ziele und die zugehorigen theoretischen und praktischen Inhalte des Programms. Zusatzlich wurden Kriterien fur die Eignung einer Statte zur Erlangung der Zusatzqualifikation und fur die Qualifikation des Leiters formuliert. Der Ablauf der Zusatzqualifikation wird in einem Logbuch dokumentiert. Die Akkreditierung der Zentren und der Leiter erfolgt durch eine Kommission „Zusatzqualifikationen in der Kardiologie“ der DGK. Fur die Zeitdauer von 2 Jahren gelten Ubergangsregelungen. Dieses strukturierte Programm zur optionalen Erlangung der Zusatzqualifikation soll einer optimalen Patientenversorgung dienen sowie die Attraktivitat der Speziellen Rhythmologie innerhalb der Kardiologie erhohen.

ZusammenfassungDie Diagnostik und Therapie des Vorhofflimmerns ist eine besondere klinische Herausforderung und besitzt große Bedeutung für die Primär- und Sekundärprävention des ischämischen Schlaganfalls. In den vergangenen zwei Jahren wurden relevante klinische Studien veröffentlicht, wobei insbesondere die multizentrischen und randomisierten Phase-III-Studien zu dem oral verfügbaren Thrombininhibitor Dabigatran und den Faktor-Xa-Antagonisten Rivaroxaban und Apixaban als Meilensteine anzusehen sind. Diese neuen Antikoagulanzien sind den verfügbaren Vitamin-K-Antagonisten im Hinblick auf die Prävention von Schlaganfällen ebenbürtig bzw. teilweise überlegen. Noch offene Fragen zu den neuen Antikoagulanzien werden diskutiert und erste Empfehlungen für die tägliche Praxis gegeben. Des Weiteren werden relevante Aspekte zur Schlaganfallprävention bei Vorhofflimmern mittels rhythmuserhaltender bzw. nicht medikamentöser Therapieverfahren dargestellt. Neben Studiendaten zu Dronedaron werden die Relevanz der linksatrialen Katheterablation sowie des interventionellen bzw. operativen Vorhofohrverschlusses diskutiert.

The German Competence Network on Atrial Fibrillation (AFNET) is a national interdisciplinary research network funded by the Federal Ministry of Education and Research (BMBF). AFNET was initiated in 2003 and aims at improving treatment of atrial fibrillation (AF), the most frequent sustained cardiac arrhythmia. AFNET has established a nationwide patient registry on diagnostics, therapy, course and complications of AF in Germany. The data analyzed to date demonstrate that patients with AF are likely to have multiple co-morbidities, such as hypertension, valvular heart disease, coronary artery disease, diabetes mellitus and advanced age. Oral anticoagulation is provided to the majority of patients in accordance with the recommendations given by guidelines. Further areas of research deal with the optimal duration of antiarrhythmic therapy following electrical cardioversion of atrial fibrillation and the value of strategies to prevent arrhythmogenic changes, such as fibrosis in the atria, for prevention of further episodes of atrial fibrillation. Additional registry projects were established for patients with catheter-based interventional therapy of atrial fibrillation and surgical ablation to define success, complications and long term results of these recently developed procedures more clearly. Data and insights gathered from these projects were used to further develop standards of care in two international conferences.

Background Nitric oxide (NO) – a major signalling molecule of the vascular system – is constitutively produced in endothelial cells (EC) by the endothelial NO synthase (eNOS). Since a reduced NO synthesis is an early sign of endothelial dysfunction and NO delivering drugs are used to substitute the impaired endothelial NO production, we addressed the effect of exogenous NO on eNOS in human umbilical venous endothelial cell cultures. Materials and methods The synthetic NO donor DETA/NO (trade name, but in the following we refer to detNO), that releases NO in a strictly first order reaction with a half life of 20 h, was used in our experiments. Results Short-term (20–30 min) detNO treatment of EC increases the Ser 1177 phosphorylation of the constitutively expressed endothelial NOS and the production of endogenous NO generated by eNOS from [ 3 H]arginine. The phosphorylation of eNOS is Akt-dependent and completely reverted by the phosphatidylinositol3 kinase (PI-3K) inhibitor LY294002. A prolonged continuous exposure of EC to detNO 150 μmol L –1 over a period of 24–48 h causes a reversible cell cycle arrest at G1-phase associated with a larger cell volume and increased cell protein content (hypertrophic phenotype of EC). The eNOS protein and mRNA of the hypertrophic cells and the generation of endogenous NO are reduced but eNOS phosphorylation could still be elevated by stimulation with vascular endothelial growth factor. Conclusions Our data explain clinical studies describing a short-term but not a long-term benefit of NO treatment for patients with cardiovascular risk factors. The results could be a rational approach to develop a generation of NO donors accomplishing a retarded release from NO donors that mimic the low continuous pulsatile stressinduced release of endogenous NO.

Drug-induced proarrhythmia is a serious medical problem that causes relevant morbidity and mortality. It is also a relevant problem for the development of novel pharmacological compounds. Therefore, there is a need for sensitive, specific and high-throughput preclinical tests to detect a risk for drug-induced proarrhythmia early in the development of new drugs. The review focuses on the potential role of transgenic models with altered repolarisation but without overt structural heart disease for drug-induced proarrhythmia screening. Today, selected murine models with alterations in K+, Na+ channels and ankyrin are available. In the future, transgenic rabbit and Zebra fish models may also be used.

Atrial fibrillation is a common and in most patients recurrent arrhythmia. Atrial fibrillation can increase mortality and causes at times severe symptoms in affected patients. Timely initiation of sustained oral anticoagulation is indicated in patients with atrial fibrillation at risk for stroke to prevent thromboembolic complications. Patients at risk for stroke can be identified by clinical characteristics using validated score systems, e.g., the CHADS(2) score or the Framingham score. Drugs that slow AV nodal conduction can improve symptoms associated with high ventricular rate. Cardioversion can acutely terminate atrial fibrillation in almost all patients, but many patients suffer from recurrent atrial fibrillation. The prevention of arrhythmia recurrences ("rhythm control therapy") is indicated in patients with severe arrhythmia-related symptoms. Antiarrhythmic drugs can approximately double the maintenance rate of sinus rhythm. Other drugs that were not primarily developed as antiarrhythmic agents, e.g., ACE inhibitors, sartans, and possibly statins, can further improve maintenance of sinus rhythm in selected patient groups. Catheter-based isolation of the pulmonary veins is a recently developed intervention that can cure some forms of atrial fibrillation. It is likely that a multimodal therapeutic approach will in the future allow rhythm control therapy to become more effective.

Background Transforming growth factor (TGF- β 1 ) is postulated to play an important role in maintaining the structure and function of arterial tissue and protection against development of arteriosclerosis. The TGF- β 1 -induced production of a stable extra-cellular matrix-rich plaque phenotype is suggested to be part of the protection against a switch to an unstable rupture-prone arteriosclerotic plaque. Materials and methods This study addresses the question of whether the expression profile and the type of extra-cellular matrix (ECM) generated by TGF- β 1 stimulation have the structural feature of a fibril-rich stable matrix. Seventeen genes codings for ECM components of human coronary smooth muscle cells (SMCs) after a 24-h stimulation by TGF- β 1 have been analyzed. Results Real-time RT-PCR was used to quantify the mRNA of genes under investigation. It was found that after TGF- β 1 stimulation (a) the up-regulation of COL1A1-specific mRNA was associated with increased [ 3 H]proline incorporation into the α -1 and -2 chains of collagen type I, (b) the up-regulation of biglycan- and syndecan-1-specific mRNA corresponded to an increased [ 35 S]sulphate and [4,5- 3 H]leucine incorporation into the biglycan molecule and to an increase of syndecan-1 protein, (c) the up-regulated FGF-2 gene accounted predominantly for the ECM-bound subfraction of FGF-2-protein and (d) fibronectin and thrombospondin exhibited a significantly higher mRNA level. In contrast collagen XIV, a minor collagen type, and the proteoglycan decorin were down-regulated. The down-regulated decorin changed its structure by elongation and reduced GlcA to IdoA epimerization of the dermatan sulphate side-chain as judged by [ 35 S]sulphate metabolic labelling experiments. No significant changes in response to TGF- β 1 were observed for the collagen types III, VI and XVI, for versican, perlecan and the syndecans-2 and -4. Conclusions It was concluded from the data that the TGF- β 1 -induced formation of a highly specific multicomponent extra-cellular matrix on coronary arterial SMCs could provide in vivo mechanical strength to the neointima in arteriosclerotic lesions and to the fibrous cap overlying the lipid core.

The correct diagnosis of a wide complex tachycardia (WCT)—QRS duration > 120 ms—remains a challenge despite numerous established criteria for the differentiation of ventricular from supraventricular tachycardia (SVT) with aberrant conduction. Making the correct diagnosis is important for the acute as well as long term management of patients with WCT. The objective of the present review is to discuss the major causes as well as clinical and electrophysiologic criteria of WCT (table 1) in patients without structural heart disease. View this table: Table 1 Causes of wide complex tachycardias (WCTs) in patients without structural heart disease Broad categories of WCTs include ventricular tachycardia (VT), SVT with abnormal intraventricular conduction, and ventricular paced rhythms. A lack of underlying structural heart disease does neither exclude a VT nor imply a benign prognosis. However, if a patient has had similar episodes during previous years, SVT is more likely than VT. Termination of a tachycardia by the Valsalva manoeuvre or adenosine injection also suggests a supraventricular origin, although some VT can also be terminated by these manoeuvres (for example, fascicular VT). A WCT in a patient who is alert and haemodynamically stable is not necessarily of supraventricular origin. The clinical presentation depends on the haemodynamic consequences it produces. These depend partly on tachycardia rate, the degree of myocardial dysfunction, the circumstances and suddenness of initiation, and autonomic factors. Physical examination in a patient presenting with WCT may indicate haemodynamic distress (low blood pressure, heart failure or cardiogenic shock). When cardiac output and blood pressure are maintained and/or when the tachycardia is short lived, the arrhythmia may present as palpitations, breathlessness or just discomfort. Intraventricular conduction delay can result from heart rate changes, as well as from fixed pathological lesions in the conduction system. In patients with pre-existing or “fixed” (present during the normal baseline rhythm) bundle branch block (BBB), …

The congenital long QT syndrome (LQTS) is characterized by a prolonged QT interval on the surface electrocardiogram and an increased risk of recurrent syncope and sudden cardiac death. Mutations in seven genes have been identified as the molecular basis of LQTS. beta-blockers are the treatment of choice to reduce cardiac symptoms. However, long-term follow-up of genotyped families with LQTS has been rarely reported. We have clinically followed a four-generation family with LQTS being treated with beta-blocker therapy over a period of 23 years. Seven family members were carriers of two amino acid alterations in cis (V254M-V417M) in the cardiac potassium channel gene KCNQ1. Voltage-clamp recordings of mutant KCNQ1 protein in Xenopus oocytes showed that only the V254M mutation reduced the IKs current and that the effect of the V417M variant was negligible. The family exhibited the complete clinical spectrum of the disease, from asymptomatic patients to victims of sudden death before beta-blocker therapy. There was no significant reduction in QTc (556 +/- 40 ms(1/2) before therapy, 494 +/- 20 ms(1/2) during 17 years of treatment; n = 5 individuals). Of nine family members, one female died suddenly before treatment, three females of the second generation were asymptomatic, and four individuals of the third and fourth generation were symptomatic. All mutation carriers were treated with beta-blockers and remained asymptomatic for a follow-up up to 23 years. Long-term follow-up of a LQT1 family with a common mutation (V254M) being on beta-blocker therapy was effective and safe. This study underscores the importance of long-term follow-up in families with specific LQT mutations to provide valuable information for clinicians for an appropriate antiarrhythmic treatment.

Der plotzliche Herztod ist eine haufige Todesursache. Er wird vor allem durch tachykarde Herzrhythmusstorungen verursacht. Angeborene genetische Veranderungen von kardialen Ionenkanalen, Proteinen des kontraktilen Apparats, der intrazellularen Calciumspeicher oder von Zell-Struktur-Proteinen konnen angeborene arrhythmogene Erkrankungen verursachen. Bei der Herzhypertrophie und der Herzinsuffizienz treten adaptative Veranderungen der Genexpression und Proteinfunktion auf, die arrhythmogene Folgen haben. Teilweise finden sich ahnliche molekulare Mechanismen der Arrhythmogenese bei erworbenen adaptativen und angeborenen arrhythmogenen Erkrankungen.

Eine 18-jahrige Patientin mit antiepileptischer Medikation wurde morgens leblos im Bett aufgefunden, vom Notarzt bei dokumentiertem Kammerflimmern reanimiert und auf die Intensivstation verbracht. Dort wurde nach EKG-Kriterien die Diagnose eines Long-QT-Syndroms (LQTS) gestellt. Im weiteren Verlauf verstarb die Patientin am hypoxischen Hirntod. Die erweiterte Anamnese ergab, dass die Patientin zuvor rezidivierende Synkopen erlitten hatte, die als epileptische Anfalle gedeutet wurden. Die 17-jahrige Schwester der Patientin war acht Wochen zuvor aus ungeklarter Ursache am plotzlichen Herztod verstorben, ebenso eine Tante (Zwillingsschwester der Mutter) mit 37 Jahren. Ein EKG-Screening bei der Familie brachte sechs weitere Familienmitglieder mit LQTS zu Tage. Eine molekulargenetische Analyse bei diesen fuhrte zur Identifizierung einer nicht-bekannten Mutation (888 delG insAA) im LQT2-Gen (HERG), die zu einem Aminosaurenabbruch (360X) auf Proteinebene in der Untereinheit des IKr-Kanals fuhrt. Die Kasuistik verdeutlicht einige klassische Aspekte des LQTS (typischer adrenerger Triggermechanismus, klassische Fehldiagnose "Epilepsie") und zeigt neue Erkenntnisse wie die Moglichkeit einer genotypischen Zuordnung aus phanotypischen EKG-Charakteristika. Der Fall reprasentiert ein ungewohnliches Beispiel eines LQTS mit hochmaligner Penetranz, welches aggressive Therapiemasnahmen bei den uberlebenden Familienmitgliedern erforderte.

About three years ago, the German Government initiated a complete change in the reimbursement system for costs of the in-hospital treatment of patients. A commission of representatives from every component of the German health system decided to adapt the Australian refined Diagnosis Related Groups (AR-DRG system). The AR-DRG system was selected as it would fit best to the German system and because of its high flexibility and preciseness reflecting severity of diseases and treatments. In October 2002, the first German Diagnosis Related Groups (G-DRGs) were calculated from the data of about 116 hospitals. These data now allow first analyses in how far a correct and precise grouping of patients in specific hospital settings is indeed performed and corresponds to the actual costs. Thus, we thoroughly calculated all costs for material and personnel during the in-hospital stay for each patient discharged during the first 4 months of 2002 from our cardiological department. After performing the grouping procedure for each patient, we analyzed in how far inhomogeneous patient distribution in the DRGs occurred and which impact this had on costs and potential reimbursements. Several different problems were identified which should be outlined in this work regarding three G-DRGs: costs of patients who received an implantable cardioverter defibrillator (F01Z) were markedly influenced by multimorbidity and additional expensive interventions which were not reflected by this G-DRG. Use of numerous catheters and expensive drugs represented a major factor for costs in patients with coronary angioplasty in acute myocardial infarction (F10Z) but seemed to be not sufficiently included in the cost weight. A specific area of patient management in our department is high frequency ablation of tachyarrhythmias which is included in other percutaneous interventions (F19Z). Complex procedures such as ablation of ventricular tachycardia or new innovative procedures as ablation of atrial fibrillation were associated with high costs leading to inadequate reimbursement. Furthermore, problems in the associated codes for diseases and procedures became apparent. Opportunities for future optimization such as specific new DRGs, splitting of DRGs, or the impact of changes in reimbursement for high-outliers were discussed.

Wir berichten uber den Langzeitverlauf eines kombinierten fusiformen Aneurysmas der Arteria subclavia dexter sowie des Abgangs des Truncus thyreocervicalis (3,2×2,8×2,2cm (Breite×Hohe×Tiefe)) bei einem 33-jahrigen Patienten. Bereits perinatal wurde der klinische Verdacht auf das Vorliegen einer Aortenisthmusstenose geausert, allerdings zum damaligen Zeitpunkt kein Interventionsbedarf gesehen. Die weitere Entwicklung des Kindes verlief zunachst normal, bis im Alter von 11 Jahren der Patient erneut aufgrund nach sportlicher Aktivitat verspurten Schwindelgefuhls kardiologisch vorgestellt wurde. Bei klinisch evidenter Progression wurde eine Herzkatheterdiagnostik durchgefuhrt, die eine juxtaductale Aortenisthmusstenose zeigte. Diese wurde konsekutiv mittels End-zu-End-Anastomose 1981 operativ korrigiert. Daneben zeigte sich bereits eine aneurysmatisch veranderte Arteria subclavia dexter, wobei diesbezuglich ein konservatives Procedere vorgeschlagen wurde. Der Patient stellte sich in regelmasigen Abstanden zu einer Verlaufskontrolle in unserer Ambulanz vor und ist seitdem vollstandig asymptomatisch. Der vorliegende Bericht zeigt den nunmehr uber 20-jahrigen asymptomatischen Verlauf eines fusiformen Aneurysmas der Arteria subclavia dexter unter Einbeziehung des ebenfalls fusiform aneurysmatisch veranderten Abgang des Truncus thyreocervicalis und bietet einen Uberblick der Literatur zu diesem Thema.

A low high-density lipoprotein-cholesterol (HDL-C) is an established indicator for increased risk of coronary heart disease (CHD). Multiple functional relationships between HDL and CHD have been discussed. We tested the clinical relevance of some of these relationships in a cross-sectional coronary angiography (CA) study of 87 post-menopausal women between 48 and 73 years. In addition to established cardiovascular risk factors we measured concentrations of phosphatidylcholine (PC) and sphingomyelin (SPM) in HDL as indirect markers of cholesterol efflux capacity, the serum activity of the paraoxonase (PON) as a measure of the antioxidative capacity and serum concentrations of insulin/C-peptide and C-reactive protein (CRP) as indirect markers of insulin sensitivity and inflammation, respectively. Upon multivariate analysis of data from 55 women with angiographically assessed CHD differed from 32 women with angiographically excluded CHD, HDL-SPM had the strongest association with the presence of CHD among all HDL-related parameters. It was also the only HDL-related parameter which had a significant and independent correlation with the number of coronary stenoses. As HDL-SPM was previously shown to correlate with cholesterol efflux capacity of plasma, we conclude that reduced cholesterol efflux capacity is an important factor accounting for the inverse association between HDL-cholesterol and CHD.

Das Jervell- und Lange-Nielsen-(J-LN)Syndrom ist eine besondere Form des kongenitalen QT-Syndroms. Im Gegensatz zum autosomal-dominant vererbten Romano-Ward (R-W)Syndrom liegt neben der charakteristischerweise mit Synkopen einhergehenden Verlangerung des QT-Intervalls zusatzlich eine Innenohrschwerhorigkeit (sog. surdokardiales Syndrom) und ein autosomal rezessiver Erbmodus vor. In jungster Zeit konnten die zugrundeliegenden genetischen Defekte bei einem Teil der an der Erkrankung leidenden Familien aufgeklart werden. Bei den kurzlich identifizierten Genen KCNQ1 und KCNE1 handelt es sich um die gleichen Gene, die auch bei Patienten mit R-W-Syndrom Mutationen aufweisen. Es ergeben sich allerdings Unterschiede im Vererbungsmodus; eine rezessiv homozygote Vererbung und eine kombinierte Heterozygotie konnen differenziert werden. Die vorliegende Arbeit fasst klinische und genetische Gemeinsamkeiten und Unterschiede des J-LN-Syndroms verglichen mit dem R-W-Syndrom sowie das diagnostische und therapeutische Management der J-LN-Patienten zusammen.

In selected patients, biventricular pacing leads to improvement in left ventricular (LV) performance, especially in the presence of pre-existing marked asynchrony of LV contraction. Improvements are sustained in the great majority of cases, and are accompanied by reduced symptoms, increased walking distance and reduced need for hospitalization. The degree of asynchrony of LV contraction and the amount of myocardial scarring are important parameters that determine the response to cardiac resynchronization therapy (CRT). Improvements in haemodynamics are due not to a positive inotropic effect of pacing but rather to elimination of an unsynchronized energy-wasting contraction pattern. Mortality trials are in progress to assess the effect of CRT on total mortality, arrhythmic mortality and mortality from heart failure.

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001[1]. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.

There is an ongoing debate whether female gender is associated with increased cardiovascular morbidity and mortality, especially after coronary interventions. The impact of gender on the outcome of patients undergoing emergency coronary artery bypass grafting (CABG) for failed PTCA was analyzed. Clinical and procedural data of all patients who underwent PTCA and subsequent emergency CABG at our institution from 1989 to 1998 were assessed. During these 10 years, 6681 PTCA procedures were performed, 1312 in women (19.6%). Subsequently, 110 patients underwent emergency CABG of whom 32 were females (29.1%). Postoperatively, 9 women and 5 men died (mortality 12.7%). Women presented with higher age (61.2 +/- 2.1 vs. 58.3 +/- 1.0 years, n.s.), smaller height (1.61 +/- 0.01 vs. 1.76 +/- 0.01 m, p0.0001), lower weight (67.7 +/- 2.4 vs. 82.1 +/- 1.2 kg, p0.0001), smaller body surface area (1.70 +/- 0.04 vs. 1.98 +/- 0.02 m2, p0.0001), and higher comorbidity as expressed by their Cleveland score (7.9 +/- 0.3 vs. 7.1 +/- 0.2, p = 0.013). The risk for failure of PTCA with subsequent emergency CABG was higher in women than in men (2.4% vs. 1.5%, p = 0.012, odds ratio 1.66) as well as for postoperative death (28.1% vs. 6.4%, p = 0.004, odds ratio 4.39). Women had longer in-hospital stays (19.7 +/- 4.2 vs. 12.9 +/- 1.3 days, p = 0.044). Logistic regression analyses found lower weight (p = 0.003), higher number of diseased coronary vessels (p = 0.024) and higher Cleveland score (p = 0.023) to be independent predictors of operative mortality. A Kaplan-Meier model (follow-up 5.3 +/- 2.5 years) showed an increased in-hospital mortality in women (p = 0.0034, log rang test), but a comparable long-term survival. Women had an increased risk for failure of PTCA and a markedly higher operative mortality after emergency CABG. In multivariate analyses, however, gender was not an independent predictor of postoperative death.

Torsade de pointes (TdP) is a serious complication which is induced by a large variety of cardiovascular and non-cardiovascular drugs. Many clinical conditions and risk factors for the occurrence of TdP during administration of drugs with a proarrhythmic potential have been identified. All such drugs have in common that they reversibly alter myocardial repolarization due to the prolongation of the action potential (acquired QT interval prolongation) which is per se not arrhythmogenic. TdP is initiated (acquired long QT (LQT) syndrome) only when a threshold level is reached leading to early after-depolarizations (EADs) and triggered beats together with a marked dispersion in recovery of excitability. The underlying mechanisms of TdP are not yet satisfactorily elucidated but, in general, alterations in cardiac ion currents which tune the normal action potential play a major role in arrhythmogenesis. Following recent advances in molecular biology and genetics, it has become clear that in some clinical instances (e.g. congestive heart failure or cardiac hypertrophy) ion channel genes become less expressed (down-regulated) and the consequent reduced ion currents (e.g. IKr) are likely to cause prolonged myocardial repolarization. In this setting, the use of drugs with action potential-prolonging properties could possibly be harmful and could not be compensated by the normal cardiac ‘repolarization reserve’. In congenital LQT syndrome some of the same ion channel components were found to be genetically altered, suggesting that either quantitative or qualitative changes of ion currents may be involved in ventricular arrhythmogenesis through similar mechanisms (‘final common pathway’). A variable clinical expressivity and, especially, an incomplete penetrance has been found in patients carrying the same LQT genotype, even when near-relatives, which raises the question on the frequency and importance of ‘silent’ (i.e. minor functional) ion channel gene mutations that may become functionally significant in presence of action potential prolonging drugs and other coexisting factors. The observation of adverse drug reactions in apparently healthy (‘normal heart’) individuals is suggestive of a genetic susceptibility for ‘acquired’ arrhythmias. This report reviews and summarizes the recent knowledge on unapparent ion channel gene mutations and preliminary concepts about ‘acquired’ arrhythmias.

The members of the Task Force on Sudden Death dedicate this paper to the memory of our former friend and colleague, Professor Ronald W. F. Campbell. Ronnie spent his life working in the field of sudden cardiac death; he contributed much and helped many. But his own life fell victim to this very problem, sadly illustrating its unexpected nature. With Ronnie’s memory in mind the Task Force has worked diligently to describe the extent of our expanding knowledge in this field, hoping that our small contribution might help to appease his sad and sudden death.

Mutations in the human minK gene KCNE1 have been linked to autosomal dominant and autosomal recessive long-QT (LQT) syndrome, a cardiac condition predisposing to ventricular arrhythmias. minK and KvLQT1, the LQT1 gene product, form a native cardiac K+ channel that regulates the slowly delayed rectifier potassium current I(Ks). We used single-strand conformation polymorphism and sequencing techniques to identify novel KCNE1 mutations in patients with a congenital LQT syndrome of unknown genetic origin. In 150 unrelated index patients a missense mutation (V109I) was identified that significantly reduced the wild-type I(Ks) current amplitude (by 36%) when coexpressed with KvLQT1 in Xenopus oocytes. Other biophysical properties of the I(Ks) channel were not altered. Since we observed incomplete penetrance (only one of two mutation carriers could be diagnosed by clinical criteria), and the family's history was unremarkable for sudden cardiac death, the 109I allele most likely causes a mild phenotype. This finding may have implications for the occurrence of "acquired" conditions for ventricular arrhythmias and thereby the potential cardiac risk for asymptomatic mutation carriers still remains to be determined.

WEBER, M., et al.: Antitachycardia Pacing for Rapid VT During ICD Charging: A Method to Prevent ICD Shocks. In patients with ICDs, rapid VTs are usually treated with shocks. It is unknown, if antitachycardia pacing (ATP) delivered once for rapid VT during capacitor charging can avoid painful shocks without increasing the risk of syncope. In patients in whom rapid monomorphic VT (cycle length 300–220 ms) could be reproducibly induced during predischarge ICD testing, the success of cardioversion (defibrillation threshold plus 10 J) and a single ATP attempt (burst with 8 or 16 stimuli) was compared using a randomized crossover study design. Consciousness of the patients was checked by the signal from a button constantly pushed by the patient. In 20 patients (ejection fraction 0.50 ± 0.19) rapid VTs (253 ± 26 ms) were reproducibly induced. A single burst successfully terminated 11 (55%) of 20 rapid VTs, 6 episodes could not be terminated with a single burst pacing and 3 VTs accelerated. Rapid VTs not terminated by ATP were significantly faster than those that could be terminated (246 vs 258 ms, P = 0.026). Cardioversion (19 ± 3 J) terminated the VTs in all cases. No patient suffered syncope during rapid VTs. A single ATP may terminate rapid VT with cycle lengths < 300 ms in 55% of patients without increasing the risk of syncope. Therefore, in rapid VTs one attempt of ATP may be suitable as an additional therapy option during ICD capacitor charging to avoid painful shocks without compromise of safety. Thus, future ICDs should implement the option of ATP during charging of capacitors.

Objectives This study is designed to examine the immediate and short-term outcomes of patients who have undergone slow pathway ablation/modification for atrioventricular nodal reentrant tachycardia. Background Targeting the slow pathway has emerged as the superior form of treatment for atrioventricular nodal reentrant tachycardia. This technique has been found effective and is associated with a low complication rate. However, little is known of the long-term outcome of patients undergoing this procedure. Methods Over a 40-month period the slow pathway was targeted in 379 consecutive patients with proven atrioventricular nodal reentrant tachycardia. The case records of all patients were examined. Accurate follow-up data is available in 96% of patients a mean of 20·6 months after the procedure. Results The initial success rate was 97%. The incidence of complete heart block was 0·8% and the mean fluoroscopy duration was 27·3min. The recurrence rate was 6·9%. Age, number of pulses and fluoroscopy time were positively associated with either initial failure or recurrence. A total of 11·3% of patients were still taking antiarryhthmic medication at follow-up. Conclusions Targeting the slow pathway is an effective form of treatment for atrioventricular nodal reentrant tachycardia. The technique has a high initial success rate, a low complication rate and a low recurrence rate at long-term follow-up. Slow pathway modification is associated with similar success rates and recurrence rates as slow pathway ablation and may confer theoretical long-term benefits.

In recent in vivo studies using positron emission tomography (PET) our group demonstrated that the myocardial beta adrenoceptor (betaAR) density is reduced in arrhythmogenic right ventricular cardiomyopathy (ARVC) and idiopathic right ventricular outflow tract tachycardia (RVO-VT) associated with an increased presynaptic catecholamine washout. It was hypothesised that the reduction of myocardial betaAR density is secondary to an increase of local catecholamines in the myocardium resulting from the presynaptic dysfunction since circulating plasma catecholamines were demonstrated to be unchanged in these conditions. To further prove this hypothesis of an organ-limited adrenergic nervous dysfunction of the heart, this study aimed to investigate betaAR density in another thoracic organ, the lung.Pulmonary and myocardial betaAR density was measured in 7 ARVC patients, 8 RVO-VT patients and in a group of healthy controls (n = 13) using the non-selective beta-blocker [11C]-CGP 12177 and PET.Pulmonary betaAR density was similar in controls (12.4 +/- 1.7 pmol/g tissue), ARVC (11.6 +/- 1.7 pmol/g tissue, p = ns) and RVO-VT (12.8 +/- 2.0 pmol/g tissue, p = ns), whereas myocardial betaAR density was significantly reduced in ARVC (6.3 +/- 1.1 pmol/g tissue, p = 0.006) and RVO-VT (6.8 +/- 1.2 pmol/g tissue, p=0.02) as compared to controls (8.8+/-1.5 pmol/g tissue).The unchanged pulmonary betaAR density in the presence of a previously described significant reduction in myocardial betaAR density in the same patient principally supports our pathophysiological hypothesis that the myocardial betaAR density may be reduced in ARVC and RVO-VT because of an increase in local synaptic catecholamine levels due to an organ-limited presynaptic adrenergic dysfunction of the heart. Since in the present study only pulmonary betaAR density was measured, future functional studies excluding pulmonary betaAR desensitisation are required to finally prove the unchanged pulmonary sympathetic innervation in ARVC and RVO-VT.

Patienten, z.B. fur eine Therapie mit Antikoagulanzien, lassen sich hieraus nicht ableiten. Ein neuer moglicher Ansatz fur eine individuell abgestimmte Behandlung besteht in der Detektion zirkulierender Mikroemboli mittels transkranieller Dopplersonographie. Mit dieser Technik lassen sich kleinste gasformige oder solide Partikel im Blutstrom detektieren, die aufgrund der geringen Grose selbst nicht zu einem klinisch fassbaren thromboembolischen Ereignis fuhren. Ihr Auftreten korreliert aber nach den Ergebnissen zahlreicher Studien eng mit einem klinisch relevanten Embolierisiko. Zur Untersuchung wird ein Schallkopf am Kopf des Patienten befestigt, der dopplersonographisch Flusssignale der Arteria cerebri media erfasst. Diese werden akustisch und optisch auf zirkulierende Mikroemboli ausgewertet. In der Neurologie wird diese Methode bereits fur eine individuelle Risikostratifizierung von Patienten eines Hochrisikokollektivs eingesetzt, z.B. bei der Indikationsstellung zu einer Antikoagulanzientherapie oder Karotisendatherektomie. In der Kardiologie wird die Mikroembolus-Detektion bisher nicht routinemasig eingesetzt und wurde nur in geringem Mas durch klinische Studien evaluiert. In diesem Uberblick sollen die grundlegenden Prinzipien, die methodisch-technischen Voraussetzungen sowie Moglichkeiten und Grenzen der Mikroembolus-Detektion dargestellt werden. Weiterhin werden die wesentlichen Studienergebnisse zum Einsatz dieser Technik bei kardiologischen Erkrankungen und kardiovaskularen Interventionen zusammengefasst.

Antiarrhythmic Drug Efficacy in Patients with an ICD. There are a number of novel ways in which implantable cardioverter defibrillator (ICD) endpoints can he used in clinical trials to evaluate antiarrhythmic drugs. The advances in ICD technology (storage, retrieval, and accurate interpretation of ICD electrograms) expand the potential to include the use of an ICD endpoint as a clinical surrogate for sudden death. The ICD also provides the necessary safety net to test new drugs. The frequent need for‘antiarrhythmic drugs in patients already fitted with an ICD (e.g., for atrial fibrillation) necessitates knowledge of the drugs' effect on defibrillator threshold. There are interpretative problems and challenges associated with all types of ICD trials. A particular difficult issue is the degree to which the results of data on antiarrhythmic drug efficacy and safety acquired in the context of an ICD endpoint trial might he extrapolated to patient populations in which the device is not used. These and other challenging issues are discussed, with the goal of enhancing the design and interpretation of clinical trials featuring ICD endpoints.

Objectives The Cholesterol Lowering Atherosclerosis PTCA Trial (CLAPT) is a prospective, randomized trial with blinded angiographic end-points to assess the effect of 2-year's treatment with lovastatin initiated 4 weeks prior to PTCA, compared to usual care on non-dilated coronary segments and on dilated coronary lesions in male patients with total cholesterol between 200 and 300mg.dl−1who underwent elective PTCA. Methods and Results Two hundred and twenty six patients were randomized 4 weeks prior to PTCA to special care (diet plus lovastatin n=112) or usual care (diet; n=114). One hundred and ninety-nine patients underwent PTCA at baseline and were finally included in the study. Quantitative coronary angiographic assessment was performed on blinded cinefilms at baseline (PTCA) and repeated after 4 and 24 months in 91% and 81% of the patients. The primary end-point was a change in the mean segment diameter of non-dilated segments. The mean lovastatin dose was 33mg.day−1. Total- and LDL-cholesterol decreased by 21% and 29% in the special care group and by 7% and 11% in the usual care patients. After 2 years, the mean segment diameter of non-dilated segments decreased by 0·03mm in the usual care group and 0·004mm in the special care group ( P =0·27). The decrease in the mean segment diameter of dilated lesions was 0·17mm (usual care) and 0·06mm (special care) ( P =0·04) after 4 months; 0·16mm (usual care) and 0·002mm (special care) after 24 months, respectively ( P =0·05). In both groups, the mean segment diameter of dilated lesions increased between 4 and 24 months after PTCA compared to a decrease in mean segment diameter of non-dilated segments ( P 50% diameter stenosis at follow-up) occurred in 28·4% of usual care and 22·2% of special care patients ( P =0·17). Conclusions Lovastatin reduced the progression of dilated lesions in men with elective PTCA. Independent of treatment allocation, the dilated lesions regressed and the non-dilated segments progressed during the study follow-up. Four weeks of pre-treatment with lovastatin did not influence the rate of restenosis. Lovastatin had no statistically significant effect on non-dilated segments.