Biomedical subjects

S Hohnloser

Publications and source records attributed to S Hohnloser.

At least 37 records · Page 2Linked to original sources

PubMed1991

Short-term variability of ventricular arrhythmia and rapid assessment of drug efficacy.

Statistical criteria for suppression and aggravation of ventricular arrhythmia were defined by means of 50 short-term drug tests performed in 24 patients. Each patient's spontaneous variability (SV) was evaluated by linear regression analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter monitoring. The response to a single oral dose of disopyramide, 300 mg, flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting 4 hours. Lidocaine was administered intravenously in incremental doses of up to 4 mg/min and was evaluated over 3 hours. Threshold values of ventricular arrhythmia corresponding to 95% confidence limits were calculated from baseline recordings and were used to ascertain the likelihood of a true drug effect. The minimum decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while an increase of at least 947% was required for a proarrhythmic effect. When these efficacy criteria were applied, 16 of 50 short-term tests revealed no drug effect. In contrast, when a 70% threshold derived from studies of daily variability was employed, only 7 of 50 trials were negative. Thus individual determination of hourly arrhythmia variability yields more stringent criteria than extrapolation from day-to-day spontaneous variation.

Aged↗

PubMed1991

Efficacy and tolerance of the new class IB antiarrhythmic barucainide: an intravenous dose-finding study.

Barucainide is a new class IB antiarrhythmic agent that was studied for efficacy and safety after intravenous administration in patients with severe ventricular arrhythmias. All patients received 80 mg/hr barucainide intravenously for 7 hours or until ventricular arrhythmias were suppressed by greater than 90%. In responders a maintenance dose was given for 24 hours, aimed to achieve steady-state conditions. At baseline and during the treatment and washout periods 24-hour Holter recordings were performed. In addition, electrocardiogram, blood pressure, and plasma concentration of barucainide were measured. In 9 of 12 patients dose titration was effective (mean dose, 185 mg). In six of nine patients arrhythmia suppression persisted during maintenance therapy (mean dose, 18 mg/hr). Plasma concentrations correlated with given doses, rather than with antiarrhythmic efficacy. During the washout period, five patients required more than 12 hours for recurrence of arrhythmias. Treatment was stopped in one patient because of proarrhythmia; one patient had moderate heat sensations. Thus barucainide is a potent class IB agent, with a favorable side effect profile.

Anti-Arrhythmia Agents↗

PubMed1991

[Arrhythmia and anti-arrhythmia therapy as prognostic risks].

The incidence of sudden death is estimated to be 0.25%/year in the industrialized world. 30 to 40% of patients are known to be at major risk before they succumb sudden death. Etiology is usually coronary heart disease (75%), dilated and hypertensive cardiomyopathy as well as valvular disease. 75% of patients dying suddenly die from ventricular fibrillation. The most common mechanism of sudden cardiac death in heart failure is sustained ventricular tachycardia deteriorating into ventricular fibrillation, the initiating factors being single ventricular beats, ventricular pairs or nonsustained ventricular tachycardia (trigger mechanism). At least 50% of patients dying during Holter monitoring have been on antiarrhythmic treatment during the time of sudden death and this percentage is increased to 70% in patients dying from torsade de pointes ventricular tachycardia. The question that has arisen is whether suppression of such arrhythmias by antiarrhythmic agents will reduce the incidence of sudden cardiac death. Unfortunately, the patient group at highest risk - low ventricular ejection fraction and high incidence of nonsustained ventricular tachycardia episodes during 24 hour-monitoring and thus, the group most in need of arrhythmia suppression - has the lowest responder rate as well as the highest incidence of serious toxicity. Until the suppression of those arrhythmias by antiarrhythmic agents is demonstrated to improve prognosis in this patient group, routine use of antiarrhythmic agents cannot be recommended in this patient population.

Anti-Arrhythmia Agents↗

PubMed1990

Detection of traumatic myocardial injury by means of simultaneous Tl-201/Tc-99m pyrophosphate tomography--report of three cases.

Trauma to the chest can result in cardiac damage, which may be missed by clinical examination because of associated injuries. Routinely performed non-invasive tests may also be non-diagnostic. Tc-99m pyrophosphate (PPi) tomography, in this study combined with Tl-201, is a promising addition to non-invasive evaluation. In three patients with cardiac injury, this technique successfully detected and localized myocardial necrosis.

Adult↗

PubMed1990

Beta-blocking agents vs. antiarrhythmic interventions in heart failure complicated by arrhythmias.

Approximately 40-50% of the patients with end-stage cardiac failure (either ischemic or nonischemic) die suddenly and unexpectedly, most probably from ventricular fibrillation. It is unclear whether the complex ventricular arrhythmias observed in large numbers of these patients were related to the mode of death. Theoretically, it seems quite reasonable to attempt to suppress the development of life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia or ventricular fibrillation) in those patients. If antiarrhythmic drug therapy is ineffective, alternative antiarrhythmic interventions (antiarrhythmic surgery or implantation of an automatic implantable cardioverter defibrillator) should be considered. In patients with so-called potentially malignant ventricular arrhythmias (e.g., nonsustained ventricular tachycardia), antiarrhythmic drug therapy remains controversial as presently there is no definitive proof that this therapy prolongs life or reduces the incidence of sudden cardiac death. In patients with end-stage cardiac failure, beta-blockade can result in a decrease in resting tachycardia, improvement in clinical heart failure symptoms, and increase in work load capacity. It remains controversial whether treatment with these agents can also improve prognosis and prevent sudden cardiac death. Therefore, at this time, only patients in the earlier stages of this clinical syndrome and with clinical signs of markedly increased sympathetic tone can be treated with low doses of beta-blockers.

Adrenergic beta-Antagonists↗

PubMed1990

Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin. Multicenter Ketanserin Research Group.

Efficacy and safety of ketanserin was studied prospectively in a randomized and double-blind trial involving 221 patients treated for hypertension and/or coronary artery disease. Since ketanserin has been suggested to cause QTc prolongation, we investigated the incidence and severity of this effect, as well as its influence on the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in-period, all patients were examined, measuring blood pressure, electrocardiogram (ECG) and 24-hour Holter ECG. Two thirds of the patients (n = 147) were then randomized to ketanserin, 1 week 20 mg b.i.d. followed by 3 weeks 40 mg b.i.d.; one third of the patients (n = 74) received placebo b.i.d. for 4 weeks. After 4 weeks of treatment, blood pressure, ECG and 24-hour Holter ECG were performed. In hypertensive patients, ketanserin resulted in a significant reduction of systolic (mean reduction: -17 +/- 2 mm Hg; p less than 0.0001) and diastolic blood pressure (-12 +/- 1 mm Hg; p less than 0.0001) as compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean value: 400 to 418 ms; p less than 0.01) but not with placebo (399 vs. 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QTc prolongation greater than 30 ms (p less than 0.01). QTc was not prolonged to greater than 500 ms in any patient. During Holter monitoring 128/147 patients (ketanserin group) and 61/74 patients (placebo group) had ventricular premature beats; in 42 (ketanserin group) and 13 patients (placebo group) ventricular pairs and tachycardia were documented. Incidence and severity of the ventricular arrhythmias after 4 weeks of treatment were not different between the ketanserin and placebo groups. No sustained ventricular tachycardia occurred in any patient after ketanserin treatment. Thus, though ketanserin prolonged QTc in one third of the patients, the drug was not arrhythmogenic or antiarrhythmic.

Aged↗

PubMed1990

[Scintigraphy using 111In-labeled antimyosin in Churg-Strauss vasculitis with myocardial involvement].

A case of Churg-Strauss vasculitis in a young woman is reported. Diagnosis was confirmed by muscle biopsy. Affection of lungs, kidneys and skin was evident. In addition, myocarditis was suspected on clinical evidence. A highly positive scintigraphy with 111In-antimyosin enabled diagnosis and assessment of damage to the myocytes. With a heart-to-lung ratio of 3.0 the accumulated activity in the myocardium was higher than usually found in myocarditis. This finding supports the hypothesis of an additional ischemic necrosis.

Adult↗

PubMed1990

[Predictive value of programmed electrostimulation in patients with spontaneous idiopathic ventricular tachycardia].

In contrast to patients with organic heart disease, there are only few data available on the incidence and type of inducible arrhythmias during programmed electrical stimulation (PES) in patients with spontaneous ventricular tachycardia (VT) but without evidence of underlying heart disease. Additionally, no consensus has been achieved in these patients on the most appropriate stimulation protocol required to reproduce the clinical arrhythmia. In a prospective study we analyzed in 40 patients without idiopathic VT, incidence and type of inducible VT, as well as the mode of initiation during a right ventricular PES protocol with 1-2 (part I) and three extrastimuli (part II). Twelve patients had spontaneous sustained monomorphic VT (group A), 28 patients were studied with spontaneous non-sustained VT (group B). During PES, a non-sustained polymorphic VT was induced in 3/12 patients (group A, 25%) and in 10/28 patients (group B, 36%); a non-sustained monomorphic VT was induced in 5/12 patients (group A, 41%) and in 4/28 patients (group B, 14%). In all 7/12 patients (59%) of group A with inducible sustained monomorphic VT, the arrhythmia was initiated with 1-2 extrastimuli. In group B, only 2/28 patients (7%) were induced to a sustained monomorphic VT. When the clinical arrhythmia was exercise-related, 5/6 patients (83%) in group A and 7/13 patients (54%) in group B were induced to a VT, while 2/6 patients (33%) in group A and 1/13 (8%) patients in group B were induced to a sustained monomorphic VT. Isoprenaline was not effective to increase the incidence of sustained monomorphic VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Incidence and clinical relevance of QT prolongation caused by the new selective serotonin antagonist ketanserin.

Efficacy and safety of ketanserin were studied prospectively in a randomized, double-blind trial involving 221 patients treated for hypertension or coronary artery disease, or both. Since ketanserin has been suggested to cause QTc prolongation, the incidence and severity of this effect were investigated, as was the incidence of malignant ventricular arrhythmias during Holter monitoring. After a 1-week run-in period, all patients were examined: blood pressure was measured and electrocardiograms and 24-hour Holter electrocardiograms were obtained. Two thirds of the patients (n = 147) were then randomized to receive ketanserin for 1 week (20 mg twice daily) followed by 3 weeks of 40 mg twice daily; one third of the patients (n = 74) received placebo (twice daily) for 4 weeks. After 4 weeks of treatment, blood pressure, electrocardiograms and 24-hour Holter electrocardiograms were repeated. In hypertensive patients, ketanserin significantly reduced systolic (mean reduction 17 +/- 2 mm Hg, p less than 0.0001) and diastolic blood pressure (12 +/- 1 mm Hg, p less than 0.0001) compared to baseline, and to the placebo group (p less than 0.005 for systolic and diastolic blood pressure). The QTc interval was prolonged with ketanserin (mean 400 to 418 ms, p less than 0.01) but not with placebo (399 vs 402 ms). In the ketanserin group 30% of patients and in the placebo group 8% of patients had QTc prolongation greater than 30 ms (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1989

Antiarrhythmic efficacy and tolerance of oral propafenone in patients with frequent ventricular arrhythmias: experience of a multicentre study.

In a multicentre study efficacy and safety of propafenone 450 mg day-1 and 750 mg day-1 was studied in 97 patients with frequent ventricular premature beats (VPB greater than 30 h-1). 70 patients suffered from organic heart disease, in 27 patients no organic heart disease was present during an initial work-up. After a 1-week washout period, all patients underwent 24 h Holter monitoring. Patients were then treated by propafenone 450 mg day-1 and controlled for 24 h Holter, ECG, blood pressure, blood chemistry and side-effects after 1 week of treatment. At this time, 35 patients were responders (reduction of VPB greater than 84%, of ventricular pairs greater than 90% and of ventricular tachycardia 100%). The mean reduction of VPB in all patients was 60%, of ventricular pairs 88% and of ventricular tachycardia 100%. When treatment was continued for 3 weeks 20/35 patients (56%) were still responders. The mean reduction of VPB was 83%. In 42 non-responders to 450 mg day-1 the dose was increased to 750 mg day-1. Of these patients, 17 (41%) became responders after 3 weeks of treatment; the mean reduction of VPB increased from 17% (first week, 450 mg day-1) to 63% (750 mg day-1). Ventricular pairs were reduced by 80%, ventricular tachycardia by 100%. Side-effects occurred in 11/97 patients and limited therapy in six patients. The most frequent complaints were dryness of the mouth, nausea, tiredness, headache and gastrointestinal upset. In conclusion, propafenone in a dose of 450-750 mg day-1 seems to be an effective and safe antiarrhythmic agent in the majority of patients.

Administration, Oral↗

PubMed1989

[Validation of a discontinuously recording, digital long-term ECG system (Siemens-Sirecust 802/850) using a single beat analysis].

Using beat-to-beat analysis we studied the annotation of 44 data-bases of the Massachusetts Institute of Technology (MIT) in comparison to the classification performed by a new microprocessor of a 24-h-ambulatory electrocardiographic device, which is based on real-time analysis and a solid-state ECG documentation. QRS detection was performed with an accuracy of 99%. Sensitivity and positive predictive accuracy were 70% and 87% for supraventricular ectopy. Using a fixed prematurity index of 80%, ventricular ectopy with a total of 7,845 beats was identified with a sensitivity of 64% and a positive predictive accuracy of 97%. With the additional consideration of late premature ventricular beats (PVB) sensitivity increased to 91% with a positive predictive accuracy of 96%. A sensitivity of more than 80% for singular PVB was achieved in 28/33 databases (85%), a similar positive accuracy was achieved in 27/33 databases (82%). Altogether, ventricular pairs and ventricular tachycardia resulted in a sensitivity of 83% and 76%, respectively, and in a positive predictive accuracy of 87% and 73%, respectively. Sensitivity exceeded 80% for ventricular pairs in 11/15 databases (77%) and for ventricular tachycardia in 10/14 databases (71%); similar results were observed for the positive predictive accuracy with 11/15 (73%) and 9/14 (64%) databases. In 42/44 databases and in all databases for arrhythmias of Lown class IVA and IVB, Lown classification was determined correctly. The Sirecust-Holter-ECG-system, a new device with real-time analysis and solid-state memory results in an accuracy for singular and complex ventricular arrhythmias, comparable to some of the presently available Holter systems.

Arrhythmias, Cardiac↗

PubMed1989

[Ventricular arrhythmia in silent myocardial ischemia--diagnosis and clinical relevance].

Silent myocardial ischemia and ventricular arrhythmias were known to be independent risk factors in patients with coronary artery disease. This has become more important since the technique of Holter monitoring has been improved and has demonstrated a high incidence of silent myocardial ischemia in the majority of patients with coronary artery disease, as well as a close relation to the occurrence of sudden cardiac death. Unfortunately, prospective data on the interaction of both risk factors are missing. We therefore studied patients undergoing exercise-testing, percutaneous transluminal angioplasty and 24-h-Holter-monitoring to assess such an interaction. During exercise testing the total incidence of ventricular arryhthmias in patients with asymptomatic ST segment depression was 42%; 6% of patients had frequent ventricular arrhythmias, 6% had ventricular pairs, and 1% had ventricular tachycardia. The incidence was similar to patients with symptomatic ST depression, but was 3.2-times higher as compared to patients without ST segment depression. During 103 attempts of percutaneous transluminal angioplasty, in 26 patients ventricular arrhythmias occurred, the incidence of ventricular tachycardia was 1-3%. No difference was observed for symptomatic and asymptomatic attempts. In 36 patients with severe coronary stenosis (greater than 90%) 24-h-Holter-monitoring showed 145 episodes of myocardial ischemia with a total duration of 967 min; two-thirds of episodes were asymptomatic. The incidence was similar in patients with symptomatic and asymptomatic episodes of myocardial ischemia, but 30 to 50-times higher as compared to the interval with ischemia. In summary, episodes of myocardial ischemia have a higher risk of ventricular arrhythmias, however, there is no difference between symptomatic and asymptomatic myocardial ischemia.

Arrhythmias, Cardiac↗

PubMed1988

Noninvasive evaluation of indecainide for serious ventricular tachyarrhythmia.

Indecainide, a new class 1C agent, was administered to 16 patients with a history of ventricular fibrillation or ventricular tachycardia. Evaluation of drug effect consisted of acute testing with 125 mg followed by a period of maintenance therapy. Efficacy, as evaluated with both ambulatory monitoring and exercise testing, was defined as total elimination of runs of ventricular tachycardia, greater than 90% reduction in couplets and greater than 50% decrease in ventricular premature complex. During acute drug testing 9 of the 16 patients responded to the drug. Four patients did not receive maintenance therapy with indecainide, because of toxic side effects. Of the remaining 12 patients, 7 responded to indecainide based on monitoring, 5 responded judged by exercise testing and 4 when both monitoring and exercise testing were considered. There was no correlation between dose, blood level of drug and effect on arrhythmia. In this small group acute drug testing did not appear to predict the response to the drug during maintenance therapy. Neurologic side effects were reported by 5 patients. Aggravation of arrhythmia occurred in 5 patients, 3 of whom had this complication during acute drug testing and 2 during maintenance therapy. Left ventricular ejection fraction, measured before and during therapy, decreased from an average of 43% to 35% (p less than 0.005). A reduction was observed irrespective of baseline left ventricular function. Indecainide is an effective antiarrhythmic agent in a small number of highly selected patients with serious ventricular arrhythmia, but potentially serious side effects limit its usefulness.

Adult↗

PubMed1988

Mode of death in idiopathic dilated cardiomyopathy: a multivariate analysis of prognostic determinants.

A total of 110 patients with idiopathic dilated cardiomyopathy were followed prospectively for 53 +/- 8 (range 41 to 69) months to determine prognostic factors identifying patients at risk for sudden death or death from congestive heart failure. During the follow-up period 39 patients died, 14 of congestive heart failure and 25 suddenly. The incidence of cardiac death after 1 year was 18%, after 2 years 35%, and after 4 years 39%. Multivariate logistic regression analysis identified four independent prognostic factors: left ventricular ejection fraction, cardiac index, number of ventricular pairs/24 hours, and atrial rhythm (sinus rhythm or atrial fibrillation). With the final model of logistic regression 77 of 88 patients (88%) could be classified correctly as being at risk for death from chronic heart failure or sudden cardiac death. Patients who were likely to die of congestive heart failure were characterized by a markedly impaired left ventricular function (measured in terms of left ventricular ejection fraction, cardiac index, or both) and a low number of pairs/24 hours. The association between frequent complex ventricular arrhythmias and depressed left ventricular function identifies patients who are at risk for sudden death. The presence of atrial fibrillation significantly increases the risk of sudden death and death from congestive heart failure.

Adult↗

PubMed1988

Prediction of efficacy and tolerance of oral mexiletine by intravenous lidocaine application.

In a controlled crossover trial, 15 patients with frequent ventricular arrhythmias were treated with lidocaine to predict efficacy and safety of oral mexiletine. After an initial control period, patients received intravenous lidocaine (bolus infusion of 200 mg/20 min followed by 3.6 gm/24 hr and for 7 days oral mexiletine (200 mg four times a day). Efficacy was controlled by 24-hour Holter monitoring (responders = suppression of single premature ventricular beats [PVB] greater than 84% and of complex PVB greater than 90%). After lidocaine, 10 of 15 patients (67%) were responders (mean PVB reduction: 97%). After mexiletine, five of 15 patients (33%) were responders (mean PVB reduction: 81%); efficacy was closely related to the plasma concentration. When efficacy of both agents was compared, lidocaine infusion had a positive predictive value of only 50%; however, the negative predictive value was 100%. Thus in nonresponders to lidocaine, mexiletine is very likely to fail in the suppression of ventricular ectopy.

Administration, Oral↗

PubMed1988

[Diprafenone--comparative study of anti-arrhythmia therapy with propafenone].

Diprafenone is a new antiarrhythmic agent with a dominant local anesthetic action and additional beta-sympathicolytic activity. In a randomized study, we analyzed the antiarrhythmic efficacy and tolerance of diprafenone (450-600 mg/day) in comparison to that of propafenone (450-500 mg/day) in ten patients with frequent and complex ventricular premature beats. After an initial control period, all patients received either diprafenone 450 mg/day or propafenone 450 mg/day for 5 days. In the case of a drug response (VPB suppression greater than 84%, suppression of ventricular pairs greater than 90%, suppression of ventricular tachycardia greater than 100%), after a wash-out period of 7 days patients were treated with the second antiarrhythmic medication for 5 days. In the case of nonresponsiveness, the dose of diprafenone and propafenone was increased to 600 mg/day and treatment continued for a second 5-day period. During the control period and at every drug administration, 24-h-Holter monitoring and ECG were performed, and plasma concentration and side effects were checked. After individual dose titration, 7/10 cases were effectively treated with diprafenone (mean dose: 471 mg; mean VPB suppression: 92%) and 5/10 cases with propafenone (mean dose: 540 mg; mean VPB suppression: 80%). Altogether four patients reported side effects, mainly gastrointestinal, which limited therapy in one patient in each group. Compared to propafenone, diprafenone had a strong effect on AV-nodal and ventricular conduction intervals; however, in no patient was therapy limited by these changes. Thus, also in comparison to propafenone, diprafenone is effective in the treatment of ventricular arrhythmias.

Aged↗

PubMed1988

Coronary thrombolysis in man with pro-urokinase: improved efficacy with low dose urokinase.

Single-chain urokinase-type plasminogen activator (scu-PA), was given to 20 patients with acute myocardial infarction first alone (group I; n = 9) and then in combination with an initial bolus injection of 200,000 units of urokinase (group II; n = 11). In group I, scu-PA was administered in a dose of 15 mg up to 60 mg as an infusion over one hour. Complete reperfusion was achieved in 3/9 patients after 50 to 60 min and partial reperfusion in an additional 2 patients. In group II, a bolus injection of urokinase and 48 mg of scu-PA over one hour were given. Reperfusion was achieved in 9/11 patients after a mean of 30 +/- 22 min. Fibrinogen, alpha 2-anti-plasmin and plasminogen levels did not change from baseline in group I. In group II, fibrinogen levels decreased slightly from 272 +/- 84 mg% to 178 +/- 82 mg% (p less than 0.05) after two hours. No bleeding complications were encountered. Reocclusion at 24 hours was evaluated in 18 patients and was not seen. It was concluded that an initial bolus of urokinase improves the efficacy and the rate of thrombolysis by scu-PA.

Adult↗

PubMed1988

[Bepridil--electrophysiologic properties of a new calcium antagonist with an anti-arrhythmia effect].

In 12 patients with recurrent pre-syncope or syncope and suspected sick sinus syndrome, the electrophysiologic properties of bepridil were tested using 1-2 extrastimuli during four basic pacing rates. Bepridil was given in a dose of 5 mg/kg body weight over 10 min. It caused no significant changes in sinus cycle length (+5%) and corrected sinus node recovery time during pacing of 100/min (-6%), 120/min (+8%) and 140/min (+4%). The conduction times PQ- (+10%) and QRS-interval (+6%) increased significantly, AH- (+8%) and HV-interval (+5%) were slightly prolonged. Antegrade Wenckebach point increased from 460 to 508 ms (p less than 0.05). The effective refractory period was prolonged in the atrium (+11%, p less than 0.05), the AV-node (+14%, p less than 0.05) and the right ventricle (6-11% at pacing rates 100-140/min, p less than 0.05 for each cycle length). In relation to the pacing rate, QTc-interval increased highly significantly (p less than 0.01) by 16% (sinus rhythm), 12% (100/min), 20% (120/min) and 19% (140/min). After a mean of 5 min after the start of infusion a doubled T-wave was observed in 11/12 patients, persisting during Holter monitoring for several hours without evidence of increased incidence of spontaneous ventricular arrhythmias. During programmed electrical stimulation with 1-2 extrastimuli, no increase in vulnerability of the right ventricle was obvious in any patient.

Adolescent↗