[Brugada-Brugada syndrome--an ECG diagnosis at a glance!].
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Diagnosis, Differential↗
Biomedical subjects
M Borggrefe
Publications and source records attributed to M Borggrefe.
Potential benefit from implantable cardioverter-defibrillator therapy in patients with and without heart failure.
BACKGROUND: Whether patients with heart failure derive a benefit from therapy with implantable cardioverter-defibrillators (ICDs) has been questioned. The purpose of this study was to investigate whether New York Heart Association (NYHA) functional class had an impact on the potential benefit from ICD therapy as assessed from data stored in the memory of ICDs. METHODS AND RESULTS: Between 1989 and 1996, 603 patients (77% men; 59% with coronary artery disease and 16% with dilated cardiomyopathy; age, 57+/-13 years; ejection fraction, 44+/-18%) were treated with an ICD with extended memory function (storage of electrograms and/or RR intervals from treated episodes) in combination with endocardial lead systems. The stages of heart failure (NYHA functional class I through III) at implantation were correlated with overall mortality and the recurrence of fast ventricular tachyarrhythmias (>240 bpm) during follow-up. The potential benefit of the device was estimated as the difference between overall mortality and the hypothetical death rate had the device not been implanted. The latter was based on the recurrence of fast and, without termination by the devices, presumably fatal ventricular tachyarrhythmias. In the overall group, a significant difference between hypothetical death rate and overall mortality was observed (13.9%, 23.5%, and 26.6% at 1, 3, and 5 years, respectively) that suggested a benefit from ICD implantation. In patients in NYHA class I, the estimated benefit, which increased over time, was 15.2%, 29.2%, and 35.6% after 1, 3, and 5 years, respectively. In patients in NYHA class II or III, the estimated benefit increased until the third year (21.8% and 21.9%, respectively) and then remained constant until the fifth year (22.9% and 23.8%, respectively). Even those patients in NYHA class III with a history of decompensated heart failure benefited from ICD implantation. CONCLUSIONS: Analysis of stored ECG data suggests that in patients with a history of ventricular tachycardia or ventricular fibrillation, ICD therapy may lead to a prolongation of life in NYHA classes I through III. The initial benefit is greatest in patients in NYHA class II and class III, but the estimated benefit might persist longest for patients in NYHA class I.
Adolescent↗
[Arrhythmogenic right ventricular cardiomyopathy. Etiology, diagnosis and therapy].
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by regional atrophy of right ventricular myocardium and subsequent replacement by fatty and fibrous tissue. The disease manifests in young adulthood with a predominance of males. Hallmarks of ARVC are ventricular tachyarrhythmias of left bundle branch block pattern which frequently occur during exercise. However, sudden death may also be the first manifestation of the disease. Characteristic findings are repolarization abnormalities and QRS prolongation in the right precordial leads of the surface ECG and regional abnormalities of right ventricular structure and wall motion. Left ventricular involvement may occur in later stages of the disease but rarely leads to progressive biventricular heart failure. Therapeutic efforts are mainly directed to the treatment of ventricular tachyarrhythmias and the prevention of sudden death. A tailored treatment strategy including antiarrhythmic drug therapy, catheter ablation and implantation of cardioverter-defibrillators may be used to improve the long-term prognosis of patients with ARVC.
Anti-Arrhythmia Agents↗
Genetic basis and molecular mechanism for idiopathic ventricular fibrillation.
Ventricular fibrillation causes more than 300,000 sudden deaths each year in the USA alone. In approximately 5-12% of these cases, there are no demonstrable cardiac or non-cardiac causes to account for the episode, which is therefore classified as idiopathic ventricular fibrillation (IVF). A distinct group of IVF patients has been found to present with a characteristic electrocardiographic pattern. Because of the small size of most pedigrees and the high incidence of sudden death, however, molecular genetic studies of IVF have not yet been done. Because IVF causes cardiac rhythm disturbance, we investigated whether malfunction of ion channels could cause the disorder by studying mutations in the cardiac sodium channel gene SCN5A. We have now identified a missense mutation, a splice-donor mutation, and a frameshift mutation in the coding region of SCN5A in three IVF families. We show that sodium channels with the missense mutation recover from inactivation more rapidly than normal and that the frameshift mutation causes the sodium channel to be non-functional. Our results indicate that mutations in cardiac ion-channel genes contribute to the risk of developing IVF.
Action Potentials↗
Syncope in patients with an implantable cardioverter-defibrillator: incidence, prediction and implications for driving restrictions.
OBJECTIVES: This retrospective study was undertaken to provide information on occurrence, risk prediction and prevention of syncope in patients with an implantable cardioverter-defibrillator (ICD). BACKGROUND: ICDs effectively terminate ventricular tachycardia and fibrillation (VT/VF). Incapacitating symptoms, such as syncope, may still occur. METHODS: We performed a retrospective analysis of data from 421 patients (clinical history, outpatient chart reviews and episode data) with mean (+/-SD) follow-up of 26 +/- 18 months. RESULTS: Of 421 patients, 229 (54.4%) had recurrent VT/VF, and 62 (14.7%) had syncope. The actuarial survival rate free of VT/VF was 58%, 45% and 37% and that for survival free of syncope was 90%, 85% and 81% at 12, 24 and 36 months after implantation, respectively. Once VT/VF had occurred, 76%, 68% and 62% of patients remained free of syncope during the following 12, 24 and 36 months, and 68%, 64% and 56% remained free of second syncope 12, 24 and 36 months after first syncope, respectively. In cases of syncope, the mean cycle length (CL) of VT was 251 +/- 56 ms. A low baseline left ventricular ejection fraction (LVEF), induction of fast VT (CL <300 ms) during programmed ventricular stimulation and chronic atrial fibrillation (AF) were associated with an increased risk of syncope. If the LVEF was >40%, fast VT had not been induced, and patients had no chronic AF; 96%, 92% and 92% of patients remained free of syncope after 12, 24 and 36 months, respectively. Once patients had a VT recurrence, syncope during the first VT and a high VT rate were the strongest risk predictors of future syncope. CONCLUSIONS: Identification of patients with an ICD with a low and high risk of syncope seems to be feasible and might help as a guide to driving restrictions in such patients.
Adolescent↗
Torsade de pointes secondary to d,l-sotalol after catheter ablation of incessant atrioventricular reentrant tachycardia--evidence for a significant contribution of the "cardiac memory".
Radiofrequency catheter ablation of a right septal accessory pathway was performed in a 66-year-old patient with incessant orthodromic atrioventricular reentrant tachycardia. Intravenous administration of flecainide, ajmaline, verapamil, and d,l-sotalol had been ineffective in controlling the tachycardia. After the ablation procedure, precordial T-wave inversion was observed during sinus rhythm. These repolarization abnormalities persisted and were suggested to represent "cardiac memory." Three days later, atrial fibrillation with a fast ventricular response developed and oral d,l-sotalol, which had been well tolerated previously on a long-term basis, was started again. However, at this time, and in the presence of the persisting repolarization abnormalities, the T waves became deeper and broader within a few hours after the introduction of d,l-sotalol. Marked QT prolongation that was paralleled by the occurrence of repeated episodes of torsade de pointes developed. Serum electrolytes were normal. Direct current cardioversion was necessary due to the degeneration of torsade de pointes into ventricular fibrillation. Further sustained arrhythmia episodes were suppressed by temporary endocardial ventricular pacing. The patient recovered without any sequela. This case demonstrates that repolarization abnormalities after catheter ablation, which may be due, at least in part, to the "cardiac memory," are not always benign but may contribute significantly to proarrhythmia.
Administration, Oral↗
[High frequency current catheter ablation of accessory conduction pathways].
Radiofrequency catheter ablation has established as the first line therapy for the curative treatment of patients with accessory pathway. Atrioventricular accessory pathways irrespective of the exact localisation can be successfully ablated in more than 90% of all cases. Severe complications associated with the ablation procedure are rare and occur in approximately 2% of patients treated. The recurrence rate after successful ablation is approximately 8 to 10%. Recurrence of accessory pathway conduction occurs almost exclusively within the first 3 months following successful ablation, late recurrences are rare. Patients with variants of accessory pathways such as atriofascicular pathways or retrogradely conducting accessory pathways with decremental conduction properties can also be cured with a high success rate. Because of its well balanced efficacy-risk profile radiofrequency catheter ablation should be recommended as the first line therapy to all symptomatic patients with accessory pathway.
Atrioventricular Node↗
Clofilium in the isolated perfused rabbit heart: a new model to study proarrhythmia induced by class III antiarrhythmic drugs.
OBJECTIVE: The clinical usefulness of class III antiarrhythmic drugs for the treatment of tachyarrhythmias is limited by their potential proarrhythmic effects, mainly torsades-depointes (TdP). The goal of this experimental study was to develop an isolated whole-heart model exhibiting typical characteristics of class III drug-induced ventricular arrhythmias. METHODS: Isolated rabbit hearts were perfused with a Krebs-Henseleit buffer containing 10 microM clofilium and then exposed to a modified Krebs-Henseleit buffer with 2.0 mM K+ and 0.5 mM Mg2+. Hearts subjected to either clofilium alone or modified buffer alone were used as controls. RESULTS: Under clofilium the QT interval increased from 187 +/- 16 to 282 +/- 33 ms. Within 8 to 25 s after the change of the perfusate, ventricular arrhythmias developed in all hearts associated with a further QT prolongation to 380 +/- 73 ms when the first ventricular extrasystole occurred. Simultaneously, the monophasic action potential durations increased relatively more during late repolarization; from 99 +/- 21 to 110 +/- 25 ms (+11%) at 50% repolarization, from 143 +/- 24 to 178 +/- 40 ms (+24%) at 70%, and from 200 +/- 30 to 275 +/- 53 ms (+38%) at 90%. The predominant rhythm was polymorphic with either two alternating or multiple QRS morphologies exhibiting the characteristic features of torsades-depointes. All control hearts stayed in normal sinus rhythm. CONCLUSION: Under the conditions selected, the isolated perfused rabbit heart represents a useful experimental approach to study the proarrhythmic effects of class III agents. This model provides a convenient way to manipulate the ionic and pharmacologic milieu in a preparation conserving the functional anatomy of the whole organ without interference by cardiovascular reflexes. It might be useful for analyzing the conditions favoring and preventing drug-induced torsades-depointes.
Animals↗
Heart rate variability and electrical stability.
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Arrhythmias, Cardiac↗
Experimental models of torsade de pointes.
Torsade de pointes is a potentially life threatening form of polymorphic ventricular tachycardia typically seen in the setting of congenital and acquired abnormal QT-prolongation. Numerous in vitro studies have investigated basic ionic mechanisms underlying delayed repolarization. The role of different ion channels and the induction of early afterdepolarizations have been studied in various cardiac cells including M cells. In addition, isolated heart models with and without electrical stimulation and/or the use of drugs which prolong repolarization have been developed in recent years. Some of these models have simulated conditions likely to exist in the clinical setting of torsade de pointes, such as bradycardia and hypokalemia. In in vivo canine and rabbit models, torsade-like polymorphic ventricular tachyarrhythmias have been induced by the administration of different agents such as cesium, neurotoxins, e.g., anthopleurin or various class III drugs under conditions designed to mimic the clinical situation. In the context of recent advances in the molecular genetics of long QT syndrome, those models which have used sodium or potassium channel blockers have gained particular interest. Based on all experimental studies it seems probable that the first beats of torsade occur due to early afterdepolarizations and triggered activity. The development of subsequent beats is less clear. Reentry based on inhomogeneity of refractoriness has been suggested as the underlying mechanism.
Animals↗
Is the implantable defibrillator indicated in patients with hypertrophic cardiomyopathy and aborted sudden death?
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Arrhythmias, Cardiac↗
Cardiac sympathetic innervation in patients with idiopathic right ventricular outflow tract tachycardia.
OBJECTIVES: This study investigated the neuronal reuptake of norepinephrine (uptake-1) and the beta-adrenoceptor density in patients with idiopathic right ventricular outflow tract tachycardia (RVO-VT). BACKGROUND: Clinical findings, such as the inducibility of ventricular tachycardia by stress or catecholamine infusion, and the therapeutic efficacy of antiarrhythmic drugs with antiadrenergic properties suggest abnormalities of cardiac sympathetic innervation in patients with idiopathic RVO-VT. METHODS: Eight patients with idiopathic RVO-VT and a total of 29 age-matched control subjects were investigated by positron emission tomography using [11C]hydroxyephedrine (HED) (volume of distribution of [11C]HED) to assess presynaptic norepinephrine reuptake; [11C]CGP 12177 (maximal binding capacity of [11C]CGP 12177) to measure postsynaptic beta-adrenoceptor density; and oxygen-15-labeled water for quantification of myocardial blood flow (MBF). RESULTS: Both myocardial catecholamine reuptake and beta-adrenoceptor density were significantly reduced in patients with idiopathic RVO-VT. The volume of distribution of [11C]HED in patients with RVO-VT was (mean +/- SD) 41.0 +/- 13.5 versus 71.0 +/- 18.8 ml/g in control subjects (p < 0.002). The maximal binding capacity of the beta-adrenoceptor antagonist [11C] CGP 12177 was 6.8 +/- 1.2 pmol/g in patients with RVO-VT versus 10.2 +/- 2.9 pmol/g in control subjects (p < 0.004). There were no significant differences in MBF at rest (0.98 +/- 0.14 vs. 0.97 +/- 0.24 ml/min per g, p = NS) between patients with RVO-VT and control subjects. CONCLUSIONS: The findings of the present study suggest that myocardial beta-adrenoceptor downregulation in patients with RVO-VT occurs subsequently to increased local synaptic catecholamine levels caused by impaired catecholamine reuptake.
Adult↗
Cerebral hemodynamics during induced tachycardia in routine electrophysiologic studies: a transcranial Doppler study.
Supraventricular and ventricular tachyarrhythmia are established causes of syncope. We investigated the mean blood flow velocities (Vmean) of the middle cerebral arteries (MCA) during routine cardiac electrophysiologic studies in patients with supraventricular and ventricular tachyarrhythmias in order to evaluate the changes in cerebral hemodynamics associated with pre-syncopal and syncopal states. Thirty-two patients with a history of supraventricular (n = 14) or ventricular (n = 18) tachyarrhythmias were investigated in the nonsedated, post-absorptive state in supine position. Vmean was assessed in both MCAs by means of transcranial Doppler under resting conditions, during atrial and ventricular pacing at constant rates (n = 28) and during induction of tachyarrhythmia (n = 4). Mean arterial blood pressure (MABP) and heart rate were also recorded. Seven patients suffered pre-syncope at a heart rate of 187 +/- 45 bpm (mean +/- SD) with an average drop of 44% in the Vmean MCA, and statistically insignificant changes in MABP. Five patients suffered syncope during tachyarrhythmia (mean heart rate 283 +/- 42 bpm) with a reduction of 69% in the Vmean MCA. MABP could be assessed in two of those patients and showed a drop of 15 and 43 mmHg, respectively. During tachyarrhythmia pre-syncope and syncope are associated with an average reduction in Vmean MCA by 44% and 69%, respectively. The decrease in MCA blood flow velocity is a more important predictive factor for the development of pre-syncope and syncope than the MABP.
Adult↗
Drug-related torsades de pointes in the isolated rabbit heart: comparison of clofilium, d,l-sotalol, and erythromycin.
Torsades de pointes is a potentially life-threatening form of polymorphic ventricular tachyarrhythmia typically seen in the presence of repolarization-prolonging agents. We investigated this particular form of tachyarrhythmia in the isolated, perfused rabbit heart. The experimental model was designed to reproduce conditions that are clinically known to be associated with an increased propensity to the development of torsades de pointes. The class III agent clofilium (1 microM) and d,l-sotalol (10 microM), as well as the antibiotic erythromycin (30-150 microM) were infused in the presence of either normal (5.88 mM) or low (1.5 mM) potassium concentration in sinus-driven or atrioventricular (AV)-blocked hearts. Ventricular tachyarrhythmias spontaneously emerged in the clofilium-, d,l-sotalol-, and erythromycin-treated AV-blocked hearts. The episodes showed typical features of torsades de pointes found in humans. They developed within 4-12 min after the onset of infusion, were normally nonsustained, and only rarely degenerated into ventricular fibrillation. Electrical stimulation at cycle lengths <600 ms and perfusion with MgSO4 suppressed arrhythmic activity. In the d,l-sotalol- and erythromycin-treated hearts, torsades de pointes occurred only in the presence of hypokalemia and bradycardia, whereas, in the presence of clofilium, bradycardia alone caused torsades de pointes. Monophasic action-potential recordings demonstrated early afterdepolarizations in endocardial and epicardial recordings. Thus the isolated AV-blocked rabbit heart represents a model for studying drug-related torsades de pointes and its mechanism.
Animals↗
Divergent effect of acute ventricular dilatation on the electrophysiologic characteristics of d,l-sotalol and flecainide in the isolated rabbit heart.
INTRODUCTION: The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide. METHODS AND RESULTS: The isolated rabbit heart was used as a model of AVD. The ventricular size and, therefore, the diastolic pressure were modified by sudden volume changes of a fluid-filled balloon placed in the left ventricle. Pacing was performed alternately using epi- and endocardial monophasic action potential (MAP)-pacing catheters at cycle lengths from 1,000 to 300 msec. d,l-Sotalol (10 microM) resulted in a significant (P < 0.05) lengthening of refractoriness (+13.5% +/- 3.1%), MAP duration (+14.9% +/- 3.2%), and QT interval (+15.5% +/- 4.1%) (mean +/- SEM at 1,000 msec). These effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg reduced refractoriness and left ventricular MAP duration. In comparison with the control group with the same extent of AVD, d,l-sotalol still led to a significant prolongation of repolarization for all cycle lengths except 300 msec, so that its effects were not absolutely but relatively preserved. In contrast, flecainide (2 microM) had no significant effects on refractoriness or MAP duration. It led to a significant, rate-dependent increase of pacing thresholds (+47.6% +/- 8.2%), prolongation of QRS (+48.8% +/- 5.6%), and conduction time (+78.6% +/- 8.6%) (mean +/- SEM at 300 msec). In the flecainide group, AVD significantly increased the normal rate-dependent prolongation of QRS (+16.7% +/- 5.5%) and conduction time (+17.1% +/- 4.3%). CONCLUSION: Our data demonstrate that, during AVD, the Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of slowing conduction is exaggerated. This may contribute to flecainide-related proarrhythmia in certain clinical situations.
Action Potentials↗
Philosophy of antiarrhythmic approaches to ventricular tachyarrhythmias close to the 21st century.
The scientific basis and the reasoning underlying the changes in antiarrhythmic approaches to ventricular arrhythmias during recent decades are discussed. The early enthusiasm in the use of antiarrhythmic drugs in patients after myocardial infarction to prevent sudden cardiac death was severely affected by the results of the Cardiac Arrhythmia Suppression Trial (CAST) which show an increased mortality of patients on sodium-channel antagonist antiarrhythmic drugs. A transient euphoria for drugs that prolong repolarization received criticism after premature termination of the Survival With Oral D-sotalol-trial (SWORD). Recently, attention has focused on the use of the implantable cardioverter defibrillator in both secondary and primary prevention of sudden death. In contrast, catheter ablation, although very useful in supraventricular tachycardia, still plays a limited role in the management of ventricular tachyarrhythmias in the presence of organic heart disease.
Anti-Arrhythmia Agents↗
Drugs versus devices in controlling ventricular tachycardia, ventricular fibrillation, and recurrent cardiac arrest.
Patients with symptomatic ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death remain at high risk for arrhythmia recurrence. In recent years, strategies to treat these patients have changed. Concerns about the proarrhythmia risk and uncertain efficacy of class I agents have resulted in a shift in interest to non-class I antiarrhythmic drugs such as sotalol and amiodarone. Both drugs have class III antiarrhythmic properties (i.e., both lengthen repolarization and refractoriness); however, each also has its own additional electrophysiologic effects. Prospectively designed, randomized studies have shown that both sotalol and amiodarone have more potent antiarrhythmic actions than class I agents. However, even as the advantages of sotalol and amiodarone have been recognized, enthusiasm for nonpharmacologic modes of treatment, particularly the implantable cardioverter-defibrillator (ICD), has also markedly increased. The ICD has been shown to decrease dramatically the incidence of sudden death, which may lead to the reduction of total mortality. Whether patients with life-threatening ventricular tachyarrhythmias should be treated first with antiarrhythmic agents or with an ICD is an important question. The results of recent studies suggest that treatment with an ICD is more effective than electrophysiologically guided treatment with class I agents. However, results of prospectively designed randomized studies comparing the efficacy of the ICD with that of sotalol and amiodarone must become available before definitive recommendations can be made concerning the use of the ICD as first-line therapy in patients with ventricular tachycardia/ventricular fibrillation or aborted sudden cardiac death. In addition, there may be a significant role for the use of antiarrhythmic drugs in conjunction with ICDs.
Amiodarone↗
Antiarrhythmic therapy--future trends and forecast for the 21st century.
This article discusses recent changes in antiarrhythmic therapy, with a focus on nonpharmacologic therapy (electrode catheter ablation, implantable cardioverter-defibrillators [ICDs]), and puts them into perspective for the coming years. The treatment of supraventricular tachycardias and tachycardia involving accessory pathways is likely to remain the domain of catheter ablation. With promising new techniques under investigation, the spectrum of arrhythmias that can be cured will probably be expanded. Treatment of life-threatening ventricular arrhythmias is likely to remain the domain of the ICD in the foreseeable future. With the safety net of the ICD in place, new antiarrhythmic drugs or other forms of antiarrhythmic therapy can be developed and tested.
Anti-Arrhythmia Agents↗