Effect of oxprenolol on ventricular arrhythmias: the European Infarction Study experience.

In 736 patients, 24 hour electrocardiographic recordings were performed 14 to 36 days after acute myocardial infarction before the start of randomized treatment with 320 mg of slow release oxprenolol (n = 358) or placebo (n = 378). Follow-up 24 hour electrocardiographic recordings were obtained 5 to 12 days (median 10) and 3, 6 and 12 months after the first administration of the study medication. Oxprenolol-treated patients had a significantly lower daytime heart rate as compared with the placebo group, whereas no difference was found at night. At baseline, 22.1% of the patients allocated to oxprenolol treatment and 29.6% of the placebo group had more than 30 ventricular extrasystoles in 1 hour at least once during 24 hour monitoring; multiform ventricular extrasystoles were present in 58.4 and 62.7%, ventricular couplets in 29.6 and 33.9% and ventricular tachycardia (3 or more consecutive ventricular extrasystoles) in 21.5 and 20.9% of the oxprenolol-treated and placebo-treated patients, respectively. During the 1 year follow-up period, the prevalence of these arrhythmias did not change significantly in either treatment group. There was a trend toward a reduction in the daytime frequency of ventricular couplets in the oxprenolol group. After 3 and 6 months, only multiform ventricular extrasystoles were significantly less frequent in the oxprenolol group than in the placebo group (47.4 and 42.7% versus 59.7 and 57.9%, respectively). Twelve months after the acute event, however, multiform ventricular extrasystole frequency was the same in both groups of patients (52.1 versus 51.0%, respectively). Thus, oxprenolol had a weak suppressant effect on ventricular tachyarrhythmias in survivors of myocardial infarction.

Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy.

The incidence and prognostic significance of ventricular arrhythmias identified by 24-hour ambulatory electrocardiography (Holter) was prospectively assessed in 74 patients with idiopathic dilated cardiomyopathy (IDC). The criteria for diagnosis of IDC were based on clinical and cardiac catheterization findings. Holter monitoring was performed at the time of entry into the study. Patients were followed for 2 to 21 months (mean 11 +/- 3). Frequent ventricular premature complexes (VPCs) (greater than 1,000/24 hours) were seen in 35%, and complex VPCs (Lown grade III and IV) in 87% of the patients. Forty-nine percent of the patients had nonsustained ventricular tachycardia (VT) consisting of 3 to 32 beats with rates from 110 to 230 beats/min, and 20% had ventricular pairs. No correlation was found between clinical symptoms or the degree of left ventricular (LV) impairment and the number of ventricular pairs or episodes of VT. During follow-up, 19 patients died, 7 from congestive heart failure (CHF) and 12 suddenly. Patients who died suddenly had significantly more episodes of VT, ventricular pairs or total VPCs (p less than 0.01 each) compared with survivors and those who died from CHF. No significant differences were found between patients who died from CHF or suddenly with respect to LV end-diastolic pressure, LV end-diastolic volume index, LV ejection fraction (EF) and cardiac index. A linear stepwise discriminant function analysis using hemodynamic (LVEF and cardiac index) and arrhythmic (number of VT episodes and ventricular pairs) variables resulted in a meaningful separation between survivors and patients who died from CHF or suddenly.(ABSTRACT TRUNCATED AT 250 WORDS)

HBW 023 (recombinant hirudin) for the acceleration of thrombolysis and prevention of coronary reocclusion in acute myocardial infarction: results of a dose-finding study (HIT-II) by the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte.

OBJECTIVE: To define an optimal dose of hirudin that would improve early coronary artery Thrombolysis in Myocardial Infarction grade 3 (TIMI 3) patency and prevent reocclusions in patients with acute myocardial infarction treated with front-loaded recombinant tissue-type plasminogen activator (rt-PA). METHODS: Recombinant hirudin (HBW 023) was tested in a sequential dose-escalating study as adjunct to front-loaded rt-PA in 143 patients with acute myocardial infarction. The sequential model was assigned two 'decision boundaries': it triggered an increase in dosage if the 60-min TIMI 3 flow rate in a dosage group was statistically not consistent with a target patency rate of 75%, or if the deterioration in coronary blood flow (of at least one TIMI grade, from TIMI 2 or 3, from one angiography to the next) exceeded 5%. RESULTS: The decision boundary for TIMI 3 flow grade at 60 min was crossed when 18 patients were treated with 0.1/0.06 mg/kg (bolus/infusion per hour over 48 h) r-hirudin (dosage group I), 42 patients treated with 0.2/0.1 mg/kg (dosage group II), and 83 patients with 0.4/0.15 mg/kg (dosage group III). TIMI 3 flow at 60 min was 50%, 58%, and 63% in dosage groups I-III, respectively (P = 0.15). Early, complete, and sustained patency (TIMI 3 flow at 60 min, 90 min and 48 h) were 44%, 55% and 64% (P = 0.07). Reocclusion between 90-min and 48-h angiograms or reinfarction occurred in 0 to 15, two of 36, and one of 72 patients, respectively (P = 0.5). Four patients (2.8%) died in hospital and 14 patients suffered a major bleeding event, but no intracranial bleeding was encountered. CONCLUSIONS: With increasing doses of hirudin, there was a trend towards greater early and complete patency, but no clear dose--response relationship was observed. A borderline significant effect was observed with respect to early, complete, and sustained patencies. In all groups, reocclusions or reinfarctions were rare. Neither clinical nor laboratory data predicted the imbalance in haemorrhagic events observed in a subsequent, prematurely terminated, phase III trial with hirudin and rt-PA.

Carotid artery stenting in clinical practice results from the Carotid Artery Stenting (CAS)-registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).

BACKGROUND: Carotid artery stenting (CAS) for symptomatic and asymptomatic carotid stenosis seems to be on the doorstep of more widespread use. However, its feasibility and safety in clinical practice at a broad spectrum of hospitals needs to be determined. METHODS: We analyzed data of the prospective multi-centre Carotid Artery Stenting (CAS) Registry of the German Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK). RESULTS: From 7/1996 to 5/2004 1888 patients from 28 hospitals were included in the CAS Registry. The median hospital stay from CAS until hospital discharge was 3 days (quartiles: 2-6 days). Median patients age was 70 years (quartiles: 64-76 years) with 72.1% males. CAS for symptomatic stenosis was performed in 55% of cases. Patients treated with CAS suffered from coronary artery disease in 66.5%, had arterial hypertension in 91.7%, hyperlipidemia in 86.3% and 34.2% were diabetics. The intended CAS procedure was completed in 98.1% of cases. A stent was implanted in 97.3% of completed cases. The median intervention time was 43 min (quartiles: 30-60 min). During the hospital stay death rate was 0.3% (5/1888) and the rate of ipsilateral stroke 3.2% (58/1840). A contralateral ischemic event occurred in 1.4% (26/ 1840) of patients. The combined rate of all death or strokes was 3.8% (70/1841). Between 1996 and 2004 there was a steady increase in the use of protection devices during CAS (0% in 1996 and 97.9% in 2004; p for trend <0.0001). There was also an increase in the proportion of patients treated for asymptomatic stenoses (p for trend <0.0001). We observed a decrease of the combined endpoint of death or stroke from 6.3% in 1996 to 1.9% in 2004 (p for trend=0.021). CONCLUSION: The multi-centre ALKK CAS Registry data confirm the feasibility and shot-term safety of CAS even in daily clinical practice. There was a rapid penetration of the use of embolic protection devices, an increase in treatment of asymptomatic carotid stenoses and a decrease in acute complication rates from 1996 to 2004.

[Prognostic significance of noninvasively detected ventricular late potentials]. / Prognostische Bedeutung nichtinvasiv registrierter ventrikulärer Spätpotentiale.

The amplitude of delayed ventricular depolarizations, if detected from the body surface, is in the microV range. High amplification and signal averaging technique for improvement of the signal-to-noise ratio are necessary prerequisites to allow the registration of these signals. Delayed depolarizations are rather frequent findings in patients with coronary heart disease and marked left ventricular wall motion abnormalities. Additional spontaneous occurrence of ventricular tachyarrhythmias in these patients further increases the incidence of delayed depolarizations. They have also frequently been described in patients who suffer from malignant ventricular tachyarrhythmias or in whom programmed ventricular stimulation can provoke a repetitive response. Ongoing follow-up observation of altogether 1200 patients with coronary heart disease, who are involved in three prospective studies, suggest that delayed depolarizations have some prognostic significance to predict mortality from all cardiac causes and sudden death. But the predictive value of these potentials seems to be too low to draw definite conclusions or to indicate the need for specific therapy in the individual patient. The data published so far do not answer the question whether the results obtained from studies involving patients with coronary heart disease will have significance also for patients free from heart disease or for those with other than coronary heart disease.

Clinical electrophysiological properties of penbutolol: a non-selective beta-blocking agent.

The electrophysiological effects of the beta-adrenergic blocking agent penbutolol (4 mg i.v.) were studied in 15 patients by means of intracardiac recording using the extra-stimulus technique and rapid atrial pacing. The following effects were observed. (1) Significant prolongation of the sinus cycle length (16%). (2) Significant prolongation of the AV-nodal conduction time during sinus rhythm (12%). (3) Significant prolongation of the AV-nodal conduction time with increasing atrial pacing rate (16--29%). At 150/min, 4 of 7 patients with intact AV-conduction under baseline conditions developed second degree AV-block 15 to 30 min after penbutolol administration. (4) Significant prolongation of the effective refractory period of the AV-node (19%). Penbutolol had no effect on the intraventricular conduction, on intraatrial conduction or on the corrected sinus node recovery time.

[Late cardiac manifestations of Reiter's disease (author's transl)]. / Kardiale Spätmanifestationen des Morbus Reiter.

Serious cardiac late manifestations were observed in two patients with Reiter's disease 15 and 26 years after the onset of the disease. There is a striking similarity with cardiac involvement in Bechterew's disease. Including cases reported in the literature there is an interval of 4-21 years, average 15 years, between the first conclusive symptoms of Reiter's disease and cardiac late manifestations. These present as isolated aortic valve insufficiency. Valves are not affected due to inflammatory changes but due to dilatation of the valve ring and of the left ventricular outflow channel. In addition, severe disturbances of the atrioventricular conduction are seen localised both in the AV node area and in the distal His-Purkinje fibres. In both observed cases surgical aortic valve replacement became necessary 20-31 years after disease onset. One patient had to have a permanent cardiac pacemaker.

[Are anti-arrhythmia agents superior to a beta blocker in treating life-threatening ventricular arrhythmias? Preliminary results of a controlled study]. / Sind Antiarrhythmika einem Betablocker überlegen in der Behandlung lebensbedrohlicher ventrikulärer Rhythmusstörungen? Vorläufige Ergebnisse einer kontrollierten Studie.

UNLABELLED: The results of serial electrophysiologic testing in patients with sustained ventricular tachycardia or ventricular fibrillation indicate that if the arrhythmia is suppressible with antiarrhythmic drugs, the prognosis is better than when arrhythmias continue to be inducible despite antiarrhythmic drug treatment. Whether electrophysiologically guided antiarrhythmic drug therapy improves outcome or merely selects groups of patients with good and bad prognosis, is not known. To answer this question, a prospective randomized trial was conducted with 166 patients (sustained ventricular tachycardia n = 84; primary ventricular fibrillation n = 46; syncope n = 36). When the arrhythmia was inducible by programmed stimulation during control, patients were allocated to receive either electrophysiologically guided antiarrhythmic drug therapy (group I), or metoprolol (daily dose up to 200 mg) without invasive testing (group II). Patients with non-inducible arrhythmias were also treated with metoprolol (group III). RESULTS: During a follow-up of 10 +/- 8 (SD) months, there were arrhythmia recurrences in 30 patients, and sudden cardiac death in 17. Follow-up did not differ between group I (n = 59) and group II (n = 53). There was a tendency for the outcome to be better in patients of group III (n = 54) than in those of group II (Log-rank test p = 0.057). In group I, patients whose arrhythmias became suppressed did much better during follow-up than those with still inducible arrhythmias (p less than 0.0001). Thus, while invasive testing is a good predictor of outcome, electrophysiologically guided antiarrhythmic drug therapy is not better than a beta blocker in patients with sustained ventricular tachyarrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

[Computer compatible long-term ECG analysing system for quantitative detection of low grade and complex dysrhythmias--Methods and evaluation of the analysing accuracy (author's transl)]. / Rechnerkompatibles Langzeit-Ekg-Analysegerät zur quantitativen Erfassung einfacher und komplexer Rhythmusstörungen; Systembeschreibung und Untersuchung der Analysegenauigkeit.

On the basis of a commercially available analyser2) a long-term ECG analysing system for quantitative detection of the following events was developed: all QRS complexes, ventricular premature beats (VPB), VPB with different coupling intervals (including the R/T phenomenon), paired VPB, salvos of VPB, ventricular tachycardias, ventricular bigeminy, supraventricular premature beats, supraventricular tachycardias, and asystoles. These dysrhythmias are detected simultaneously at 60-fold speed and counted within predeterminable time intervals, the results being printed out and at the same time stored on punch tape, thus allowing off-line computer processing of the data. The accuracy of the analysing system working in a fully automatic mode was evaluated by comparison to the results obtained by two cardiologists. The predictive value of the analyser was 99.9% for all QRS complexes and 97.2% for aberrantly shaped QRS complexes. The corresponding values of the sensitivity were 99.7% and 95.3%. For paired VPB or salvos of VPB and ventricular bigeminy the predictive value was 91.8% and 95.1%, respectively, the sensitivity being 93.4% and 87.9%, respectively. For the detection of asystoles, in spite of a 100% sensitivity a predictive value of only 45.6% was found. Therefore these events may well be detected automatically, but the false positive counts will have to be sorted out by visual inspection on the oscilloscope or ECG write-out.

[Intravenous streptokinase infusions in acute myocardial infarction. Restoring patency of occluded thrombotic coronary vessels (author's transl)]. / Intravenöse Streptokinase-Infusion bei akutem Myokardinfarkt. Wiederöffnung thrombotisch verschlossener Herzkranzgefässe.

Intravenous treatment over 30 minutes with 500 000 U streptokinase was given to 21 patients with acute myocardial infarction. Serial measurements of serum CK-MB activity made recanalisation of the infarcted artery likely in 3 patients. Selective coronarography was performed in 18 patients during the acute infarction phase. Angiographic follow-up investigations were done 24 hours and after 3 weeks. In 3 cases only subtotal occlusion of the infarcted coronary artery was seen during the acute phase. A thrombus demonstrated in two patients could be lysed. In 8 out of 15 patients with complete coronary artery occlusion the infarcted vessel was reopened 20-60 minutes after onset of intravenous streptokinase infusion. In a further 4 patients recanalisation was observed 60-140 minutes after passing a guide wire or during an additional intracoronary infusion of streptokinase. The infarcted vessel remained occluded in 3 patients, one of whom died following myocardial rupture. In 12 patients with recanalisation of the infarcted artery during the acute phase a premature maximum of serial CK-MB serum activity was seen after 13.5 +/- 2.9 hours in comparison with 20.9 +/- 5.3 hours in 122 patients treated conventionally. Serial enzyme determinations allow indirect conclusions as to a rapid recanalisation of an infarcted blood vessel.

[Demonstration of complex ventricular tachy-arrhythmias by long-term ECG monitoring: relationship to duration of monitoring]. / Nachweis komplexer tachykarder ventrikulärer Rhythmusstörungen im Langzeit-EKG.

Continuous long-term ECG monitoring over three 24-hour periods was undertaken in 42 patients with complex ventricular tachy-arrhythmias. The arrhythmias were divided by degree of severity. The lowest degree was assigned to frequent ventricular extrasystoles (more than 20 per hour). The next degree was assigned to ventricular bigeminal rhythm, while runs of extrasystoles were assigned the highest degree. In 30 patients the highest arrhythmia level was reached within the first 24-hours, in nine after a further 24 hours, in three during the third 24-hour period. Comparing the three periods of registration there were differences between the various arrhythmias, not of kind but of frequency of the arrhythmia. Simple VES and the complex forms differed in their occurrence: although of 33 patients with frequent VES (more than 20/h) 30 also had runs of VES, in six patients with runs of VES the frequency of extrasystoles was low (less than 20/h). In 70% of cases 24-hour monitoring was sufficient to record the highest level of ventricular tachy-arrhythmia. If, however, no severe arrhythmias have been recorded during this period, increasing the duration of monitoring to 48-hours can be useful. A third period or more is of little further value.

[Standardized psychological stress test for the provocation of tachycardial ventricular arrhythmias. Comparison with long-term ECG and stress ECG]. / Standardisierter psychischer Belastungstest zur Provokation tachykarder ventrikulärer Rhythmusstörungen. Vergleich mit Langzeit-EKG und Belastungs-EKG.

The effect of a standardized psychological stress test on frequency and severity of ventricular extrasystoles was compared in 42 patients with the results of 24-hour ECG monitoring and of an exercise ECG test. Frequent ventricular extrasystoles (greater than 1/min) occurred in the 24-hour-ECG in 22, in the psychological stress test in 24 and on physical exercise in 22 patients. 24-hour monitoring gave the only positive finding in ten, the psychological stress test in six, the exercise test in four. Complex arrhythmias (coupled or runs of ventricular extrasystoles) occurred in the 24-hour ECG in 30, with the psychological stress test in 16 and the exercise test in 12 patients. The 24-hour ECG was alone positive in 16, the psychological test in two, the exercise test in one. Thus in an individual patient the psychological stress test may provoke additional arrhythmias which are not recorded in either the 24-hour ECG or after exercise. The findings point to an independent significance of the psychological stress test in the diagnosis of simple and complex ventricular arrhythmias.

[A new method for the evaluation of the success of anti-arrhythmic drug therapy and a paradoxical drug-induced arrhythmogenic effect in individual patients]. / Neue Methode zur Beurteilung eines antiarrhythmischen Therapieerfolges und eines paradoxen arrhythmogenen Medikamenteneffektes beim Einzelpatienten.

The aim of this study was to develop standards to define both antiarrhythmic drug efficacy and a drug-induced arrhytmogenic effect. In 45 patients with frequent and complex ventricular tachyarrhythmias 3 continuous 24-hour Holter recordings were performed. The spontaneous variability of ventricular premature beats and ventricular pairs was calculated using a new statistical method (transformation model). If two 24-hour Holter monitoring periods, one period before and the other with antiarrhythmic therapy, are compared, at least 75% reduction of ventricular premature beats and 90% reduction of ventricular pairs is necessary to be reasonably certain that one is measuring a drug response rather than spontaneous arrhythmia reduction (p less than or equal to 0.05). On the other hand, drug-induced aggravation can be assumed if ventricular premature beats and ventricular pairs have increased by more than 144% and 227%, respectively (p less than or equal to 0.05).

[Noninvasive registration of spontaneous ventricular potentials in patients with healthy hearts and in patients with intraventricular impulsive conduction disorders. Method and results of the signal averaging technic]. / Nichtinvasive Registrierung ventrikulärer Spätpotentiale bei Herzgesunden und bei Patienten mit intraventrikulären Reizleitungsstörungen. Methode und Ergebnisse der Signalmittelungstechnik.

For registration of delayed depolarizations 50 healthy persons (age: 49.4 +/- 6.2 years) and 43 patients with bundle-branch block (age: 65.1 +/- 11.8 years; 23 of them with right and 20 with left bundle-branch block) underwent high-resolution electrocardiography at the body surface using signal-averaging technique. The findings were compared with results obtained in the 24-hour long-term ECG. In 2 normal persons (4%), delayed depolarizations were recorded whose configuration, however, differed from that of pathological findings in patients with coronary heart disease. 2 other subjects evidenced repetitive ventricular arrhythmias. Detection of delayed depolarizations in patients with coronary heart disease is indicative of an increased risk of malignant or even fatal arrhythmias. The low prevalence in healthy subjects underlines the specificity of this finding and represents the prerequisite for identifying patients with an increased risk. Delayed depolarizations were found also in 3 patients with right and 4 patients with left bundle-branch block (16.3% in all). 8 patients had repetitive ventricular arrhythmias, and one of them with a left bundle-branch block also revealed delayed depolarizations. Thus delayed depolarizations can be registered in some patients with intraventricular conduction defects. The incidence rate corresponds to that found in patients with coronary heart disease, so that detection of delayed depolarizations in this patient group is not helpful in the assessment of prognosis.

[Comparative study of the anti-arrhythmia effect of flecainide acetate and prajmalium bitartrate in patients with tachycardiac ventricular rhythm disorders]. / Vergleichende Untersuchung über den antiarrhythmischen Effekt von Flecainidacetat und Prajmaliumbitartrat bei Patienten mit tachykarden ventrikulären Rhythmusstörungen.

In an open randomized therapeutic study, 20 patients known to have frequent ventricular premature beats (VPB) and/or ventricular pairs (VP) were treated with both 2 X 200 mg flecainide (F) and 4 X 20 mg prajmalium-bitartrate (P) for 3 months each. There was a drug-free interval of one week between the two therapy phases. 24-hour long-term ECG-registrations were carried out before the start of the therapy phases as well as 1 week, 1 month, 2 months and 3 months after the initiation of antiarrhythmic therapy. After one week, the group as a whole evidenced a VPB reduction of 94% under F and only 57% under P (p less than or equal to 0.05). The percentage of individual patients in whom there was a statistically significant VPB reduction was also higher under F than under P (65% vs. 40%). In the group as a whole, there was a VP reduction of 99% under F and 88% under P (p less than or equal to 0.05) after one week. Of the 13 individuals with frequent VP (over 16 VP/24 h), a significant reduction was seen in 77% under F and only 38% under P. The difference between the two antiarrhythmic agents registered after one week was also observed in the further course of therapy but could no longer be statistically confirmed for the ventricular pairs. An aggravation of ventricular arrhythmias was observed in 2 patients under F and in 3 under P.(ABSTRACT TRUNCATED AT 250 WORDS)