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Results: Out of 664159 women there were 22938 patients with hyperlipidaemia (3.5%) and 9312 patients with breast cancer. Out of the hyperlipidaemia patients, 530 patients developed breast cancer (2.3%) compared with 8782 patients developing breast cancer without hyperlipidaemia (1.4%). A logistic regression model accounting for time from first presentation to development of breast cancer showed that the presence of hyperlipidaemia increases the outcome of breast cancer by 1.64 times (95% C.I. 1.50-1.79). Conclusions: Whilst we appreciate numerous limitations of our methods, coupled with the main findings of the recent basic science research, our analysis further augments the case for the role of cholesterol in the development of breast cancer. Our data from a large clinical relevant sample further strengthens the argument to prospectively trial statins in the management of breast cancer.

Torsade de pointes (TDP) is a polymorphic ventricular tachycardia with a particular electrocardiographic pattern of continuously changing ("twisting") morphology of the QRS complex occurring in the setting of delayed myocardial repolarization (i.e., prolongation of the QT interval). TDP may develop in the setting of an idiopathic disorder (Jervell/Lange-Nielsen syndrome, Romano-Ward syndrome, sporadic long QT syndrome) or may be induced by pharmacologic agents which prolong the QT interval, as well as by other clinical circumstances under which repolarization is delayed (e.g., hypokalemia, hypomagnesemia, bradycardia) (acquired long QT syndrome). Since the treatment of TDP strongly differs from that of conventional ventricular tachycardia, correct diagnosis is critical as it guides the treating physician in selecting the appropriate mode of therapy. In this paper mainly the electrocardiographic criteria presently used for the correct identification of this unusual form of ventricular arrhythmia are presented. Additionally, the potential mechanisms and therapeutic modalities of TDP are discussed.

Radiofrequency (RF) catheter ablation has developed into a new non-pharmacological therapy for the definitive treatment of patients with cardiac arrhythmias. Although an increasing number of recent reports have indicated the widespread use of the procedure, no data are available to estimate the number of procedures performed in Europe. Furthermore, currently no data on a large series of patients are available that provide information on the risk of procedure-related complications. This report presents the results of the Multicentre European Radiofrequency Survey (MERFS) that was conducted by the Working Group on Arrhythmias of the European Society of Cardiology. The objectives of this voluntary retrospective survey were to assess the number of radiofrequency catheter ablation procedures performed in 86 European institutions from January 1987 until March 1992 and the incidence of procedure-related complications with respect to the different types of ablative procedures. A total of 4398 patients were reported on from 68 out of 86 institutions (79%) from 15 European countries that agreed to participate in MERFS. From 1987 to 1991, the number of patients who underwent RF ablation per year increased from 45 to 2000. In the first 3 months of 1992, a total of 1640 patients were reported on. The number of patients reported on in relation to the different types of ablative procedures were: ablation of atrial tachycardialatrial flutter: n = 141 (3.2%); ablation of the atrioventricular junction: n = 900 (20.5%); modification of the atrioventricular junction in atrioventricular nodal reentrant tachycardia: n = 815 (18.5%); ablation of accessory pathway: n = 2222 (50.5%); ablation of ventricular tachycardia: n = 320 (7.3%). Procedure-related complications occurred in 223 patients (5.1%). The incidence of complications in relation to the ablative procedure was: ablation of atrial tachycardia/atrial flutter: 5.0%; ablation of the atrioventricular junction: 3.2%; modification of the atrioventricular junction in atrioventricular nodal reentrant tachycardia: 8.0%; ablation of accessory pathway: 4.4%; ablation of ventricular tachycardia: 7.5%. Complications occurred significantly more often in patients who underwent modification of the atrioventricular junction in atrioventricular nodal reentrant tachycardia, when compared to ablation of the atrioventricular junction (P0.001) or ablation of accessory pathway (P0.001), and in patients who underwent ablation of ventricular tachycardia, when compared to ablation of the atrioventricular junction (P0.002) or ablation of accessory pathway (P0.02). The highest incidence of complications was reported after modification of the atrioventricular junction in atrioventricular nodal reentrant tachycardia.(ABSTRACT TRUNCATED AT 400 WORDS)

Summary: Patients with atrioventricular nodal reentry tachycardia (AVNRT) occa..ionally may demonstrate a 2: 1 infra-His block during tachycardia. However, the electrophysiologic background of this phenomenon has not been established so far. In the present study we compared the electrophysiologic parameters of 10 consecutive patients with a transient 2: l infraHis block during AVNRT of the common type (Group A) with those of 17 consecutive patients without this phenomenon during tachycardia (Group B). Transient 2: 1 infra-His block cccurred without termination of the tachycardia in all 10 patients of Group A. The tachycardia sustained despite intermittent or permanent conduction disturbance of the infrahisian tissue in 8 of these 10 patients. In comparison, the electrophysiologic parameters of 17 patients without 2: l block during AVNRT of the common type (Group B) were analyzed. A significantly longer antegrade (3 18 f 58 ms vs. 259 k 50 ms) and retrograde (308 f 59 ms vs. 239 f 20 ms) AV conduction capacity could be demonstrated in these patients. The tachycardia cycle length did not differ significantly between the two groups, although the mean tachycardia cycle length was 48 ms longer in patients of Group B. These observations demonstrate an advanced conduction capacity in patients with a transient infra-His block during AVRNT of the common type. This study underlines that the reentry circuit in AVNRT is not necessarily dependent on infrahisian tissue.

Oral anticoagulation in patients with rheumatic heart disease for prevention of systemic thromboembolism is accepted clinical practice. The incidence of stroke in patients with nonrheumatic atrial fibrillation is about five times the rate of patients in sinus rhythm. However, contradictory findings in several small retrospective studies have precluded determination of a gold standard for patients with nonrheumatic atrial fibrillation so far. Recently, the results of five prospective, placebo-controlled studies in patients with nonrheumatic atrial fibrillation treated with anticoagulation have been published. A consistent risk reduction of thromboembolism ranging from 37 to 87% in patients treated with warfarin was reported. This risk reduction occurred in excess of a relatively low incidence of intracerebral and/or fatal bleeding complications. The efficacy of prevention of thromboembolism was comparable for high intensity anticoagulation (International Normalized Ratio (INR) 2.8-4.2) and low dose anticoagulation (INR 1.5-2.7). However, fatal and/or intracerebral bleedings only occurred with INRor = 2.6. In subgroup analysis, recent congestive heart failure, arterial hypertension, and previous apoplex or arterial thromboembolism were independent clinical predictors of increased risk for thromboembolism, whereas results in patients with chronic and intermittent atrial fibrillation were comparable. In 69 patients with lone atrial fibrillation, no single event occurred in the follow-up period. Thus, lone atrial fibrillation does not seem to carry an increased risk for stroke when strict criteria for diagnosis of lone atrial fibrillation are applied. In two of the five studies, aspirin was additionally randomized. Since contradictory findings resulted, the role of aspirin for prophylaxis of stroke still needs to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

INTRODUCTION The basis for anterograde or retrograde unidirectional block of accessory pathways still remains a controversial issue. METHODS AND RESULTS Four of 19 consecutive patients (1 male, 3 female; ages 27 to 34 years) who underwent transcatheter ablation of concealed accessory pathways developed manifest preexcitation after the ablation. The location of the concealed accessory pathways in these four patients were right lateral, left posteroseptal, left posterolateral, and left lateral. Radiofrequency current was used in three of the four patients and high energy direct current in one patient. After ablation, manifest preexcitation was observed in these four patients for the first time. Manifest preexcitation developed immediately after ablation in two of the four patients and after 4 and 14 days in the other two. Detailed endocardial mapping revealed that the manifest preexcitation originated from the same location as the concealed pathways. Subsequently, catheter ablation was successfully performed in three of the four patients using radiofrequency current. One patient underwent successful surgical ablation. No recurrence of preexcitation was observed during a follow-up period of 9 to 38 months. All patients remained free of arrhythmias. CONCLUSION The basis for this unexpected emergence of preexcitation in these patients with only retrograde conducting accessory pathways deserves further investigation. Although not compared in the present study, this phenomenon has not been reported in patients who underwent surgical interruption of accessory pathways. We postulate that a lesion at the site of insertion of the accessory pathway had modified the anterograde conduction capacity.

The case of a 36-year-old woman with suspected idiopathic long QT syndrome is reported. Diagnosis was made late after syncopal attacks and several episodes of resuscitation had occurred. Although therapy with a beta-blocking agent was initiated and a cardioverter/defibrillator was implanted, the patient died, due to a hydrocephalus internus resulting in cerebral damage. Diagnostic and therapeutic problems in idiopathic long QT syndrome are discussed.

Arrhythmogenic right ventricular disease (ARVD) is a disease of unknown origin that primarily affects the right ventricle and is characterized by ventricular tachyarrhythmias which may lead to syncope and even, though rarely, sudden cardiac death. In 25 patients with ARVD, sympathetic innervation of the left ventricle was assessed by iodine-123 metaiodobenzylguanidine single photon emission tomography (123I-MIBG SPET). In addition, thallium-201 SPET was performed. The diagnosis of ARVD was made by an electrophysiological study and right and left heart catheterization including right ventricular endomyocardial biopsy. Ischaemic heart disease was excluded by coronary angiography. A group of seven patients without any evidence of heart disease served as a control group. Twenty-two of the 25 patients showed reduced uptake of 123I-MIBG. The abnormal areas were located predominantly in posterior and posteroseptal segments of the heart. No focus of increased 123I-MIBG activity could be demonstrated. No patient had signs of left ventricular involvement on left ventricular angiography. In contrast to the results of the 123I-MIBG SPET, those of 201T1 SPET were normal in 16 patients. The remaining nine patients showed areas of slight hypoperfusion not correlated with the reduced 123I-MIBG uptake. 123I-MIBG scintigraphy allows detection of left ventricular adrenergic dysinnervation in ARVD patients without morphological or functional abnormalities of the left ventricle.

Catheter ablation using radiofrequency or direct current energy was performed in 19 consecutive patients with concealed accessory pathways. Four patients developed manifest preexcitation for the first time following ablation. The concealed accessory pathways of these four patients were localized at right lateral, left posteroseptal, left posterolateral, and left lateral sites, respectively. In two patients, manifest preexcitation developed immediately after attempted ablation. In the other two patients, preexcitation occurred after 4 and 14 days. Electrophysiologic testing revealed in all four patients that the origin of manifest preexcitation corresponded to the site of the concealed pathway. Successful catheter ablation using radiofrequency current was performed in three patients. One patient preferred surgical interruption of the accessory pathway. The reason for this sudden emergence of preexcitation of these patients with only retrograde conducting pathways remains to be investigated. The anterograde conduction capacity might have been modified by damaging the site of the accessory pathway insertion.

Catheter ablation techniques have evolved as an alternative to map-guided surgery and proven effective in a variety of supraventricular tachyarrhythmias. Direct current catheter ablation has been shown to be effective in about 50 to 70% of cases. Approximately, 60% of patients with structural heart disease and monomorphic ventricular tachycardia were successfully treated using direct current ablation techniques. This overall success rate and possible risks associated with the use of direct current have stimulated the search for other energy sources appropriate for catheter ablation. Presently, only a few preliminary reports on the clinical efficacy of radiofrequency energy for the treatment of ventricular tachyarrhythmias in man exist. 23 patients with identifiable heart disease at a mean age of 52 +/- 17 years underwent radiofrequency catheter ablation. 16 patients had coronary artery disease, one patient dilative cardiomyopathy and six patients had arrhythmogenic right ventricular disease. All patients presented with chronic current sustained ventricular tachycardia. After detailed endocardial catheter mapping radiofrequency energy was applied at the site of earliest ventricular activation during ventricular tachycardia which could be entrained during fixed rate ventricular pacing at the site of origin of ventricular tachycardia. At all ablation sites a long latency between the stimulus and QRS complex was noted. Of 23 patients 18 were treated with radiofrequency alone whereas in five patients a second ablation procedure using direct current was performed. Following the ablation procedures, 14 patients (61%) remained free of ventricular tachycardia. One patient died due to congestive heart failure 21 months following ablation.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheter ablation of ventricular tachycardias was performed in a total of 80 patients whose tachycardias were considered as drug refractory and who were not considered to be candidates for antitachycardic surgery or implantation of an automatic cardioverter defibrillator. After careful endocardial catheter mapping including pacing interventions, either direct-current (DC) (n = 61) or radiofrequency current (RF) (n = 13) or both (n = 6) were applied of the "site of origin" of ventricular tachycardia or the "zone of slow conduction". 42 of 51 patients with coronary heart disease were discharged; ventricular tachycardia recurred in 8 cases, and 2 patients died suddenly. In the remaining 32 patients, there were no recurrences of ventricular tachycardia during a mean follow-up period of 12 month. Three patients died perioperatively. In 21 of 29 patients without coronary artery disease, no recurrences of ventricular tachycardia were observed (mean duration of follow-up 17 months) whereas 8 cases had a recurrence of ventricular tachycardia.

The feasibility and efficacy of pulsed radiofrequency (RF) current delivery was assessed and compared to results obtained by continuous energy delivery. Energy was delivered to ventricular preparations of isolated porcine hearts (HAT 100, 500 kHz, Osypka, FRG). In the pulsed mode, impulse duration and pause duration were varied between 50 and 500 ms. Total duration of coagulation was 30 s in all cases. The depth of induced lesions was significantly enhanced by a short impulse- and pause duration (50-70 ms) compared to continuous RF energy delivery. At long pause durations (200-500 ms) and short impulse duration, depth and diameter of lesions significantly decreased. The incidence of sudden increases in impedance was markedly attenuated when energy was delivered discontinuously. Thus, pulsed RF energy delivery can be used to enhance the depth of RF lesions. The decreased incidence of sudden rises in impedance during pulsed energy delivery further enhances the feasibility of RF coagulation. An improvement in heat transfer to deeper tissue layers can be considered as the mechanism responsible for these effects.

To determine the effects and the underlying mechanisms of sudden rise of impedance during radiofrequency (RF) catheter ablation, 60 RF applications were delivered to isolated preparations of ventricular myocardium at three different power levels (mean: 3.7, 11.3, 19.3 watts). Pulse duration was 30 s, current voltage and catheter tip temperature were continuously monitored. Impedance rise occurred during 34 of 60 applications; the incidence of impedance rise increased at higher power levels. Impedance rise was significantly more often observed when the preparations were superfused with heparinized blood compared to saline solution (p less than 0.05). Catheter-tip temperature during radiofrequency application without impedance rise was significantly lower compared to applications with impedance rise (mean = 108 degrees C vs. 121 degrees C, p less than 0.01). The increase of catheter-tip temperature and maximal-tip temperature following impedance rise was significantly higher in blood when compared to saline solution (mean = +48 degrees C vs. +13 degrees C (p less than 0.001), Tmax: 121 degrees C vs. 245 degrees C). Following impedance rise, insulation defects of the electrode catheter and vaporized crater formation of the myocardium was often observed.During radiofrequency catheter ablation impedance rise occurs following overheating of the catheter electrode (greater than 110 degrees C). After impedance rise, catheter-tip temperature markedly increases. Insulation defects of the catheter and vaporized craters in the myocardium frequently occur after impedance rise. The results have important implications for the clinical use of RF-currents for catheter ablation; energy application should be immediately stopped after the occurrence of impedance rise.

Laser-photocoagulation (LPC) of arrhythmogenic myocardium has been reported to successfully ablate ventricular tachycardia. The purpose of this study was to investigate the acute hemodynamic and electrophysiological effect of continuous laser energy (Nd:YAG, 1060 nm) applied via a 0.4-mm quartz fiberoptic on the epicardial surface of the heart in nine dogs. A total of 51 +/- 2.3 pulses was delivered in each animal to induce homogeneous tissue necrosis. Applied energy was 12.3 +/- 2.7 J/mm2, irradiated surface measured 12.6 +/- 3.0 cm2, lesion depth was 6.3 +/- 1.2 mm (range: 5.0-8.1 mm), lesion volume was 8.1 +/- 2.8 cm3 (6.8% of left ventricular [LV] mass). After LPC, epicardial stimulation threshold significantly rose from 1.0 +/- 0.3 to 10.2 +/- 4.9 mA in the border zone to nontreated tissue and from 0.9 +/- 0.4 to 32 +/- 15.7 mA in the center of the lesions. Loss of epicardial activation in the irradiated areas could be demonstrated by epicardial mapping. Ventricular extrasystoles during LPC were seen in all dogs, ventricular tachycardia in seven, and ventricular fibrillation in two dogs. After LPC, cardiac output and LV dP/dtmax significantly decreased by 14.2% and 11.2%. LPC induced predictable homogeneous tissue edema, eosinophilic staining, contraction band necrosis, and sharp demarcated hemorrhagic border zones with a sharp electrical border zone to nontreated tissue and loss of epicardial activation. During LPC, various arrhythmogenic effects could be observed. However, no persistent arrhythmic activity developed after LPC. The results confirm the feasibility of epicardial LPC of the myocardium. Although not rested in this study, LPC of arrhythmogenic tissue may also be feasible as a treatment modality of ventricular tachycardia.

In past decades, numerous experimental and clinical studies have improved our knowledge of the electrophysiological effects of sodium channel blockers, as well as of the mechanisms of arrhythmogenesis. However, the mechanisms of antiarrhythmic as well as potentially proarrhythmic drug action have been less well clarified. Sodium channel blocker agents have different effects on the normal, ischaemic, and failing heart since their antiarrhythmic actions depend on the substrate and the mechanisms of arrhythmogenesis, as well as other mostly interrelated cardiac and non-cardiac factors. Strict criteria of efficacy and safety have to be applied when sodium channel blockers are used for the treatment of ventricular arrhythmias.

The cardiopulmonary effects of constant-flow ventilation were investigated in dogs with normal heart function (control-phase, n = 14) and after development of acute myocardial ischaemia (ischaemia phase, n = 14). Heated, humidified and oxygen-enriched air was continuously delivered with an inspiratory flow rate of 1.21.kg-1.min-1 via two catheters positioned within each mainstem bronchus. Continuous positive pressure ventilation with a positive end-expiratory pressure of 0.5 kPa (5 cmH2O) was used as a reference. During control, neither continuous positive pressure ventilation nor constant-flow ventilation showed impairment of cardiopulmonary performance. Oxygenation and CO2 removal were more efficiently achieved by continuous positive pressure ventilation (P less than or equal to 0.05). Acute myocardial ischaemia was induced by occlusion of the left anterior descending (LAD) coronary artery; measurements during the ischaemia phase were performed 60 min following LAD occlusion. Myocardial ischaemia resulted in moderate changes of cardiac output, left ventricular end-diastolic pressure and dP/dtmax. Both modes of ventilation were well tolerated in the ischaemia phase, and cardiovascular performance revealed no significant differences between continuous positive pressure ventilation and constant-flow ventilation. Haemodynamic parameters could be more precisely assessed during constant-flow ventilation. Oxygenation deteriorated, but hypoxaemia did not occur in any animal and CO2 elimination remained unchanged. It is concluded that 'non-conventional' ventilation by continuous intrabronchial gas flow maintains adequate gas exchange with no adverse effects on haemodynamics in dogs with acute myocardial ischaemia. Constant-flow ventilation may be advantageous in the experimental setting to study cardiac function without cyclic heart-lung interaction due to airway pressure alterations.

The in vitro and in vivo effects of endocardial laser ablation were assessed. Energy was supplied by a Nd-YAG laser (wavelength approximately 1064 nm) and transmitted via a quartz core fiber (phi: 0.4 mm) housed within a specially designed 7 F catheter. In vitro, the effects of increasing output power (5, 10, 20, 40 watt) and impulse duration (1, 2, 4, 8 s) on lesion size were assessed in myocardial preparations of canine hearts. Preparations were superfused with saline or blood, respectively; the distance of the optical fiber to the endocardium was 5 mm. Lesion size increased in diameter (range: 0-4.0 mm) and depth (range: 0-5.2 mm) in a power- and time-dependent manner. Superfusion with blood significantly enhanced the diameter of the lesions, whereas depth of the lesions significantly decreased. In 16 anesthetized mongrel dogs, a total of 52 laser impulses (output power: 10, 20, 40 w; impulse duration: 1, 2, 4 s; energy: 10-160 J) were delivered to apical and apico-inferior sites of the left ventricle. Postmortem, 40 lesions with a diameter of 2.6-19.4 mm and a depth of 3.7-16.2 mm were found. 19 lesions revealed central vaporized craters with a depth up to 11.2 mm. Perforation of the left ventricle occurred in two cases following 80 and 160 J, respectively. In vitro and in the intact animal (in apical and apico-inferior sites of the left ventricle) endocardial laser ablation is feasible to induce distinct myocardial lesions in a power- and time-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Trans-catheteral ablation is an important therapeutic method for nonpharmacological management of various types of cardiac arrhythmias. Since its introduction into clinical practice in 1982, it has proved its efficacy in disturbance or change of the type of atrioventricular conduction and conduction along accessory abnormal atrioventricular conduction pathways. Positive results have also been attained in the treatment of some patients with ventricular tachycardia. The energy sources used for ablation include direct current pulses possessing large energy, high-frequency currents, and laser energy. Ablation with direct current and high-frequency current is already used successfully in patients, while the use of laser energy for ablation of myocardial arrhythmogenic tissue is limited mainly to operations on the open heart. The use of alternating high-frequency current has attracted particular attention in the last years. Trans-coronary chemical ablation is another recently introduced method which is not connected with the use of electric current. Only experimental and a small clinical experience with this new method has been gained to date. This survey systemasizes the current knowledge of the biophysical bases of the various method of ablation from the standpoint of the mechanisms of treatment, the methodology and the main types of tissue response. Clinical experience with trans-catheteral treatment of cardiac arrhythmias is analysed.

Myocardial ischemia and infarction are the most common substrates for life-threatening ventricular tachyarrhythmias. Experimental and clinical evidence suggests that enhanced activity of the sympathetic nervous system plays an important role in the genesis of ischemia-related arrhythmias. In animal experiments, β-blockers display significant antifibrillatory effects during the acute phase of myocardial ischemia. Preconditions for their antifibrillatory effects are high serum- and tissue-concentrations, and absence of a significant partial agonist activity. During the delayed phase of ischemic arrhythmias which starts 6–8 h after coronary occlusion, β-blockers gain significance as antiarrhythmic and potentially antifibrillatory drugs, if sympathetic activity is enhanced.

Recently, transvenous catheter ablation using radiofrequency impulses has been applied in experimental animals as well as in humans. This review describes the biophysics, mechanisms, and tissue effects of radiofrequency alternating current. Ablation of the AV-junction has been performed in experimental studies as well as in a growing number of patients. Complete AV-block or modification of the AV conduction by RF-current application can be achieved in about 45-65% of patients. Presently about 50% of patients with rightsided accessory pathways can be successfully managed using radiofrequency impulses. Certain limitations exist using a biopolar "epi-endocardial" electrode configuration for leftsided accessory pathways. Only few studies are available concerning the use of RF ablation of ventricular tachycardia foci. As most experimental investigations were carried out in structurally nondiseased myocardium, the use of this new technique in fibrotic or scarred tissue warrants further studies. Radiofrequency catheter ablation seems to be feasible and relatively safe for the treatment of otherwise drug-refractory supraventricular arrhythmias; further studies are needed to assess the safety and efficacy in patients with drug-refractory ventricular tachyarrhythmias.

Beta-blockers are effective antiarryhthmic agents for certain types of supraventricular and ventricular arrhythmias. They are able to prevent arrhythmias associated with sympathetic hyperactivity, suppress automaticity, and slow conduction in myocardial tissue with predominant slow-response activity. In animal experiments, beta-blockers have been shown to exert pronounced antifibrillatory effects following occlusion of a main coronary artery. This effectiveness may be the basis for the improved survival of patients with chronic coronary artery disease under long-term beta-blockade. Side effects are often dose-related; the optimal and minimal effective doses of the beta-blocker are critical in limiting adverse effects. As conventional antiarrhythmic agents have not been shown to reduce the risk of mortality in postmyocardial infarction patients, a broader application of beta-blockers as antiarrhythmic agents within the future, possibly in combination with class I or III drugs, seems conceivable.

Myocardial ischemia and infarction are the most common substrates for life-threatening ventricular tachyarrhythmias. Experimental and clinical evidence suggests that enhanced activity of the sympathetic nervous system plays an important role in the genesis of ischemia-related arrhythmias. In animal experiments, beta-blockers display significant antifibrillatory effects during the acute phase of myocardial ischemia. Preconditions for their antifibrillatory effects are high serum- and tissue-concentrations, and absence of a significant partial agonist activity. During the delayed phase of ischemic arrhythmias which starts 6-8 h after coronary occlusion, beta-blockers gain significance as antiarrhythmic and potentially antifibrillatory drugs, if sympathetic activity is enhanced. The presently available evidence suggests that the potentially antifibrillatory effects of beta-blockers are at least one of the major mechanisms by which these drugs may decrease mortality when given prophylactically in patients after myocardial infarction. However, it remains to be explained why beta-blockers, in a great number of prospective randomized trials, have reduced the incidence of sudden death only by an average of about 30%. This may be the result of their "specific" mechanisms acting in the setting of acute myocardial ischemia with enhanced adrenergic tone, whereas in the remaining patients other mechanisms such as a chronic arrhythmogenic substrate may be operative. A clearer separation of these various mechanisms seems mandatory in order to allow a more specific "targeted" administration of beta-blockers. This is the more important since none of the available prospective studies that used antiarrhythmic agents has shown an improvement of prognosis, but, instead showed a worsening of the mortality rate.

Diprafenon, ein Strukturanalogon des Propafenons ist ein neues Antiarrhythmikum der Klasse Ic, welches neben einer lokalanasthetischen Hauptwirkungskomponente uber zusatzliche β-sympathikolytische Effekte verfugt. Nach den bisher vorliegenden Befunden ist dabei dosisbezogen von einer zirka zwei- bis vierfachen lokalanasthetischen und β-sympathikolytischen Wirksamkeit im Vergleich zu Propafenon auszugehen (8, 9). Gesicherte Indikationen fur den Einsatz von Diprafenon als Antiarrhythmikum sind die AV-Knoten-Reentry-Tachykardie (5), supraventrikulare Tachyarrhythmien bei ventrikularer Praexzitation (5) sowie ventrikulare Rhythmusstorungen (3–5). Moglicherweise kommt der Einsatz der neuen Substanz auch fur die Therapie des paroxysmalen Vorhofflimmerns bzw. fur die Rhythmisierungsbehandlung bei chronischem Vorhofflimmern in Betracht (5).

Background Due to the investigative nature of AF catheter ablation, currently only highly symptomatic patients are treated. Remarkable success rates have been reported repeatedly. However, the follow up strategies measuring that outcome are largely based on symptomaticity. Therefore the present study aimed on analyzing the perception of AF in 114 pts. before and after a left atrial catheter ablation using the CARTO System. Methods A digital 7-d-ECG was recorded prior to ablation, right after ablation, after 3 months, after 6 months and after 12 months. During the 7-d-ECG the pts. hourly registered quality and duration of any symptoms in a certain patient's log. Palpitation, dyspnoea, dizziness and chest pain were taken as surrogates of AF. Subsequently the amount of time with symptomatic AF, asymptomatic (ASYM) AF, symptomatic SR and ASYM SR was measured. Additionally the individual AF episode was classified as either symptomatic or ASYM. Results For more than 75000 hours of ECG recording symptoms and rhythm were correlated. Prior ablation 54% of the time in AF and 22% of the AF episodes were ASYM. After ablation the proportion of ASYM AF episodes increased from 22% to 53% of all AF episodes. Watching the individual patient ASYM AF was common in 65% of all pts. with AF before and after catheter ablation. Nevertheless, the percentage of pts. with only ASYM AF during the 7-d-ECG increased from 10% prior ablation to 36% 6 months after ablation. Conclusions Pts. with highly symptomatic AF also exhibit a substantial amount of ASYM arrhythmia (54% of AF time, 22% of AF episodes). After ablation the amount of ASYM AF increased, with half of the episodes being ASYM. Furthermore, 36% of the pts. with AF recurrences at the 6 months follow up were completely ASYM during that 7-d-ECG. Our data show, that a judgement on the efficacy of percutaneus AF ablation based on patient's symptoms substantially overestimates the success rate. Objective follow up strategies, applied in a close manner, are needed for a through measurement of the real outcome.

Purpose: Recognition of the phrenic nerve (PhN) course is helpful for avoiding complications during ablation. We evaluated the PhN route along the heart using electro-anatomical mapping (EAM). Methods: In 18 patients with atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation, EAM of superior vena cava (SVC), right and left atria, and right pulmonary veins (PVs) was reconstructed using a CARTO system during sinus rhythm. The location of the PhN adjacent to the heart was defined as the site twitching of the diaphragm with pacing (5-10 voks) occurred, and that site was tagged on the EAM. Results: The PhN began at the upper limit and anterior aspect of the SVC and twisted down to the posterior aspect of the right atrium near the sinus node in 14 patients (78%), or it was located at the postero-lateral aspect of whole SVC in 4 patients (22%). In most cases (89%), the PhN could be captured at the anterior aspect of the right superior PV (RSPV) which was 8.14-3 mm inside RSPV ostium, whereas it could not be captured from the right inferior PV in any patients or from the lower right atrium in 11 patients (61%).

The case of a 30-year-old woman with polycystic disease of the kidneys and a large cyst in the interventricular septum is presented. The hypothesis of an echinococcal disease or of a cardiac manifestation of a polycystic disease was raised. The patient's history, serologic data, and the morphological aspect of the cyst did not give evidence for echinococcal disease before surgery. However, the postoperative pathological evaluation confirmed the diagnosis of a single echinococcal cyst. The presented case shows that even in cases without proven diagnosis of echinococcal disease and preexisting hereditary cysts in other organ systems, care should be taken during surgery to avoid anaphylaxis and preoperative spread of the parasite throughout the body.

Objectives. The purpose of this study was to analyze and compare the local electrograms recorded at successful and unsuccessful sites of ablation to identify the criteria that may predict successful sites and minimize unnecessary radiofrequency delivery.Background. Transcatheter ablation of accessory pathways using radiofrequency energy requires extremely precise localization of an accessory pathway.Methods. Local electrograms from 50 consecutive patients with left-sided accessory pathways who underwent transcatheter radiofrequency ablation were analyzed. During catheter ablation, localization of accessory pathways was performed in 39 pathways during pre-excited sinus rhythm and in 14 pathways during orthodromic tachycardia. A total of 429 local electrograms at target sites obtained before delivery of radiofrequency current was analyzed. A prospective study was performed in another 20 patients using the criteria derived from the retrospective study.Results. Accessory pathway conduction block was achieved in 36 (92%) of 39 pathways in which mapping was performed during pre-excited sinus rhythm and in 9 (64%) of 14 pathways in which mapping was performed during orthodromic tachycardia (p < 0.05). When mapping was performed during pre-excited sinus rhythm, a combination of four variables (that is, an accessory pathway potential, stability of local electrograms, atrial activation > 1 mV and ventricular activation preceding the onset of the delta wave) showed a 62% probability of success. In contrast, excluding these variables resulted in a 95% probability of failure (noneffective or transiently effective). The prospective study shows that the use of these criteria can significantly reduce the number of current applications. When mapping was performed during orthodromic tachycardia, recording the earliest atrial activation was the most powerful predictor of success. A stable local electrogram with a small notch on the ventricular potential, presumed to be an accessory pathway potential, may add predictive value.Conclusions. Transcatheter radiofrequency ablation is highly effective in the treatment of patients with left-sided accessory pathways. Specific characteristics of local electrograms can be important predictors of success or failure. Mapping during preexcited rhythm renders ablation more effective than does mapping during orthodromic tachycardia.

Der akute einzeitige Verschlus eines koronaren Hauptstammes fuhrt im Tierexperiment und ebenso haufig beim Menschen innerhalb der ersten 20–30 Minuten zu charakteristischen zeitlichen Anderungen der ventrikularen Vulnerabilitat mit einer zweigipfligen Haufigkeitsverteilung der Arrhythmien, insbesondere von Kammerflimmern (33).

Maligne ventrikulare Arrhythmien, speziell Kammerflimmern, die vielfach bereits innerhalb weniger Minuten nach Verschlus eines Herzkranzgefases auftreten, stellen die haufigste Ursache des plotzlichen Herztodes dar (1–3). Die im Tierexperiment nach einzeitigem abgangsnahen Koronarverschlus von 20–30 Minuten Dauer auftretenden ventrikularen Arrhythmien zeigen eine phasische Haufigkeitsverteilung (4, 5). Die Herzrhythmusstorungen treten gehauft zwischen der 2.–10. Minute (Phase Ia) und der 15.–20. Minute (Phase Ib) auf. Im Intervall zwischen beiden Phasen ist eine deutliche Abnahme der Arrhythmienintensitat zu beobachten.

Acute thrombosis of highly stenosed coronary arteries often results in acute myocardial infarction. The rationale for thrombolytic therapy is to restore blood flow before irreversible myocardial cell damage develops. In this review the results of more than 60 interventional studies in which reperfusion or "patency" rates, left ventricular function, infarct size, as well as intrahospital and long-term mortality following thrombolytic therapy were assessed, are reported and analyzed with respect to the patterns of applying thrombolytic therapy (different thrombotic agents and percutaneous transluminal coronary angioplasty). The results show that a significant reduction in infarct size, improvement in left ventricular function, and decrease in early- as well as late-mortality can be achieved when successful recanalization is established within four hours after onset of symptoms. Thrombolytic efficacy with respect to patency rates is highest after intravenous application of so-called fibrin-selective thrombolytic agents (rt-PA) and APSAC (71% and 73%), intracoronary application of streptokinase (69%), and primary percutaneous transluminal coronary angioplasty (88%). By contrast, intravenous infusion of streptokinase results in recanalization of only 56% of occluded vessels. However, the improved reperfusion rates after treatment with rt-PA or intracoronary application of streptokinase are associated with a relatively high incidence of reocclusion (up to 20%). Patients' prognosis after successful initial thrombolysis is essentially influenced by additional interventions, e.g., percutaneous transluminal coronary angioplasty and surgical revascularisation. At present, several questions about the ideal thrombolytic agents or the optimal timing of additional interventions need to be clarified. Further studies are necessary to answer these questions.

1. Among the dysionemias hyper- and hypokalemia are particularly important for clinical arrhythmogenesis. Disorders in sodium- and calcium concentrations, however, are relevant only in single cases. The impact of magnesium concentration disorders on cardiac rhythm is not yet totally elucidated. 2. In hypokalemia tachycardic arrhythmias are most important, while bradycardic and tachycardic arrhythmia can be caused by hyperkalemia. An important factor in arrhythmogenesis is the rate of development of hypo- or hyperkalemia. Hypokalemically-induced arrhythmia can be suppressed by potassium substitution. 3. Although the importance of a magnesium dysionemia for arrhythmogenesis has not been confirmed, magnesium can be used for the treatment of arrhythmias with good results. Besides an antiarrhythmic efficacy, an antifibrillatory activity is suggested in acute myocardial ischemia.

Incidence and severity of ventricular arrhythmias (VA) following transvenous catheter ablation have so far not been fully elucidated. In the present study we evaluated the comparative incidence of postablation ventricular arrhythmias following high voltage-direct current electrical ablation (DCA), radiofrequency-ablation (RFA), and laser-photoablation (LPA). Experiments were performed on a total of 26 anesthetized mongrel dogs (BW: 20-30 kg). DCA (n = 14; 150-200 J) and RFA (n = 7; 38.5-72.5 J) were performed unipolarly via a 6F USCI catheter, LPA (n = 5; 40-80 J) was delivered through a quarz core fiber (diameter 0.4 mm) housed within a special designed catheter. Energies were delivered to various sites of free wall and apical endocardium of the left ventricle. Immediately after DCA fast runs of ventricular tachycardia (VT) developed in 13 out of 14 dogs degenerating into ventricular fibrillation in two animals. Mean cycle length of induced VT was 298 +/- 86 ms. Persistent VA, morphologically mainly characterized by an accelerated idioventricular rhythm interrupted by runs of ventricular salvoes, occurred in 12 animals (mean rate: 78 +/- 13 VPB/min 3 h after ablation). During VT early endocardial activations were recorded from the ablation site. No significant correlation between total applied energy (150-550 J) and incidence of arrhythmogenic effects was observed. RFA and LPA induced ventricular salvoes and runs of non-sustained ventricular tachycardia, in one animal ventricular fibrillation occurred during RFA; however, no persistent arrhythmic activity developed after RFA and LPA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The pathophysiological basis of sudden cardiac death due to ventricular arrhythmias in acute myocardial infarction has been extensively investigated in experimental as well as in some clinical studies. Numerous clinical studies have been performed with the aim to establish the feasibility of antifibrillatory prophylaxis of sudden cardiac death by pretreatment with antiarrhythmic drugs. Using class I-antiarrhythmic drugs the reported findings were contradictory. While the antiarrhythmic efficacy of Lidocaine and other, newer class I-antiarrhythmic drugs is well established, the antifibrillatory effects of these drugs in the early phase of acute myocardial infarction remain uncertain. In clinical studies with the endpoint of mortality in patients at risk, longterm administration of orally effective class I-antiarrhythmic drugs did not prove to be superior to placebo. However, beta-sympatholytic agents have been shown to reduce mortality in patients at risk in several large clinical studies. The basic mechanism seems to be primarily a reduction in sudden cardiac death which is caused predominantly by ventricular fibrillation. The antifibrillatory properties of beta-blockers was demonstrated as well by a reduction in the number of episodes of ventricular fibrillation. The recognition of patients at risk who profit most from chronic beta-blocker therapy remains the main problem when treatment of numerous low-risk patients is avoided. In the ISIS I-study with Atenolol intravenous administration of a beta-blocker in the early phase of acute myocardial infarction has been shown to be beneficial if hemodynamic monitoring, for example using flow-directed heart catherization is performed. In general this does not apply to the treatment with calciumantagonists, especially with Verapamil and Nifedipine. These drugs do not improve prognosis of acute myocardial ischemia, obviously because of hemodynamic side effects. The antifibrillatory efficacy of Verapamil-type calciumantagonists, shown in the experimental model, could not be demonstrated in the clinical setting. Nevertheless, further clinical studies performing longterm prophylactic treatment of patients at risk before the onset of myocardial ischemia seem to be worthwhile. Concerning class III-antiarrhythmic agents, clinical experience in the setting of acute myocardial infarction is limited; hence a final conclusion about their antifibrillatory efficacy under clinical conditions at present is impossible.

Malignant ventricular arrhythmias, especially ventricular fibrillation, which often occur within minutes after occlusion of a coronary vessel, are the commonest cause of sudden cardiac death (1–3). The ventricular arrhythmias which occur in animals after coronary occlusion performed once for 20–30 minutes close to the origin of the vessel show a phasic frequency distribution (4, 5). There is a build-up of the arrhythmias between the 2nd and 10th minute (phase Ia) and between the 15th and 20th minute (phase Ib). They are distinctly less severe in the interval between the two phases.

Die Bedeutung ventrikularer Reperfusionsarrhythmien als Ursache des plotzlichen Herztodes des Menschen ist bislang ungeklart. Lediglich bei 30% der Patienten mit plotzlichem Herztod sind postmortal frische Myokardnekrosen bzw. akute Koronarthrombosen nachweisbar (12, 33). In den ubrigen Fallen konnten Spasmen normaler oder stenosierter Koronararterien bzw. eine spontane Lyse von Koronarthromben an der Auslosung der lebenbedrohlichen Arrhythmien beteiligt sein. Im Tierexperiment fuhrt eine abrupte Wiederfreigabe der Durchblutung passager okkludierter Koronargefase in Abhangigkeit von der Verschlusdauer (4; Tabelle 1) sowie von der Gefase des ischamiegefahrdeten Myokardareals (1, 45) zu morphologisch, pathogenetisch und prognostisch differenten Formen ventrikularer Rhythmusstorungen. Innerhalb der ersten 30 Minuten nach Koronarverschlus nimmt die Haufigkeit von initialem Kammerflimmern nach Reperfusion (Abb. 1) mit der Dauer der Ischamie signifikant zu (siehe Tabelle 1). Bei langeren Verschluszeiten ist sie anschliesend parallel zur Entwicklung irreversibler Zellschadigungen mit Abnahme der Erregbarkeit (12, 29) deutlich rucklaufig.

Barucainide is a new class Ib-antiarrhythmic compound which causes a reduction of the upstroke velocity and shortens the duration of the action potential in a dose-dependent fashion. The electrophysiological, hemodynamic and antiarrhythmic effects of the new drug were analyzed in experimental and clinical investigations. The results show that barucainide, in a dose range varying between 0.125-4.0 mg/kg i.v. fails to exert any significant effect on cardiac conduction and refractory times, heart rate, arterial blood pressure, cardiac output and left ventricular contractility. In a standardized animal model of ventricular arrhythmia, barucainide proved to be superior to lidocaine with respect to its antiarrhythmic potency. In a group of patients displaying chronic, otherwise therapy-resistant ventricular arrhythmias, the drug was effective in the majority of cases. Tolerance was excellent over a maximum observation period of 18 months. According to our first experimental and clinical observations, further testing of barucainide appears promising. The drug may be of particular value for treatment of ventricular arrhythmias in cases with left ventricular dysfunction, heart failure and severe conduction disturbances.