Showing papers by "Paulus Kirchhof published in 2001"

Brugada syndrome and supraventricular tachyarrhythmias: a novel association?

Abstract: Brugada Syndrome and Supraventricular Tachyarrhythmias.Introduction: The Brugada syndrome is a distinct form of idiopathic ventricular fibrillation characterized by a unique ECG pattern consisting of a right bundle branch block-like aspect and ST segment elevation in leads V1 to V3. As a high induction rate of ventricular tachyarrhythmias has been reported in Brugada syndrome, we hypothesized that this also may be true for supraventricular tachycardias in these patients. Methods and Results: Between January 1995 and December 2000, we identified 35 consecutive patients with Brugada syndrome; 26 had a history of cardiac arrest or syncope and 9 were asymptomatic. All patients underwent electrophysiologic study, including an atrial and ventricular stimulation protocol. Ten patients (29%) were found to have supraventricular tachyarrhythmias (SVT) in addition to the Brugada syndrome. These 10 patients presented with aborted sudden cardiac death (n = 3) and/or a family history of sudden cardiac death (n = 4), syncope (n = 4), or primarily with a Brugada typical ECG, a positive family history, and palpitations (n = 2). Eight of them underwent genetic testing, but only 1 had a mutation in the SCN5A gene. In 6 patients, an AV nodal reentrant tachycardia was easily and reproducibly inducible. Two patients had clinical documented and inducible episodes of an atrial tachycardia (1 in addition to an AV nodal reentrant tachycardia). One patient had paroxysmal atrial fibrillation alternating with sinus rhythm, and 2 patients with accessory pathways were identified. Conclusion: This is the first description of an association of the Brugada syndrome with SVT. Thus, the arrhythmogenic substrate in Brugada syndrome may not be restricted to the ventricular level. Palpitations in this syndrome should raise the possibility of SVT. Conversely, in patients with SVT and aborted sudden cardiac death or syncope not related to SVT, the Brugada syndrome should be considered a possible additional electrophysiologic abnormality.

Wolff-Parkinson-White syndrome associated with Brugada syndrome.

Abstract: A 30-year-old male soccer player suddenly collapsed during the break of a football match. He was found to have ventricular fibrillation and was successfully resuscitated. There was no history of prior syncope or palpitations nor a family history of sudden cardiac death. The resting electrocardiograph (ECG) demonstrated normal sinus rhythm with a short PR interval and delta waves that were positive in leads I, II, aVL, and V2 through V6, and isoelectric or negative in III, aVR, aVF, and V1, consistent with a right septal accessory pathway (AP) (Fig. 1). During electrophysiological study, there was antegrade block in the AP at a cycle length of 590 ms (Fig. 2). In addition, intermittent antegrade block in the AP was observed. After administration of orciprenaline, a supraventricular tachycardia with a cycle length of 290 ms was inducible. During this tachycardia, the earliest atrial activation was recorded near the His position; the ventriculoatrial (VA) interval was 90 ms. In the presence of orciprenaline, antegrade conduction block in the AP already occurred at a cycle length of 320 ms, which did not explain the occurrence of ventricular fibrillation. During electrophysiological study, there was intermittent occurrence of a right bundle branch block-like pattern with ST-segment elevation in the right precordial leads (Fig. 3). This ECG pattern could be unmasked by intravenous (IV) ajmaline (1mg/kg). Ventricular fibrillation was reproducibly inducible with three extrastimuli from the right ventricular outflow tract (basic pacing cycle length of 500 ms, coupling intervals: 220/200/200 ms). Discussion Patients with Wolff-Parkinson-White (WPW) syndrome, who have been resuscitated from ventricular fibrillation as a consequence of a WPW related tachyarrhythmia, are invariably found to have atrial fibrillation with rapid ventricular response (minimum preexcited RR interval , 250 ms) at baseline electrophysiological study. Therefore, the finding of a minimum preexcited RR interval of # 250 ms has been proposed as a sensitive marker for identification of patients at risk of sudden cardiac death. In the present patient, intermittent antegrade conduction was observed during sinus rhythm and early antegrade block during atrial stimulation at a cycle length of 590 ms. In addition, after challenge with orciprenaline, antegrade block was noted at 320 ms. Therefore, atrial fibrillation with rapid ventricular response leading to ventricular fibrillation is very unlikely. However, it can not be excluded that an orthodromic atrioventricular reentrant tachycarWolff-Parkinson-White Syndrome Associated with Brugada Syndrome

Effects of Thoracic Epidural Anesthesia with and without Autonomic Nervous System Blockade on Cardiac Monophasic Action Potentials and Effective Refractoriness in Awake Dogs

Abstract: Background The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia itself may have modified the effects of TEA. This study investigates right atrial and ventricular repolarization by recording monophasic action potentials after TEA in awake dogs. The authors hypothesized that an antiarrhythmic role of TEA exists, which may be related to a direct effect of TEA on myocardial repolarization. Methods The hypothesis was tested in an in vivo canine model, in which atrial and ventricular myocardial action potential duration and refractoriness are recorded by means of monophasic action potential catheters. Results Thoracic epidural anesthesia significantly increased ventricular monophasic action potential duration for cycle lengths shorter than 350 ms. Changes in monophasic action potential duration were paralleled by a concomitant prolongation of effective refractory period (ERP) at higher rates so that the ratio of ERP to action potential duration was unaffected. Conclusions This model helps to study the role of TEA on ventricular repolarization and arrhythmogenicity. Because lengthening of repolarization and prolongation of refractoriness may, in some circumstances, be antiarrhythmic, TEA may be protective against generation of ventricular arrhythmias mediated, e.g., by increased sympathetic tone. The results also imply that the beneficial role of TEA might be stronger at the ventricular site as compared with the atrium. At atrial sites there was only a trend toward prolongation of repolarization even at short cycle lengths.

Load-induced changes in repolarization: evidence from experimental and clinical data

Abstract: The high incidence of arrhythmias in patients with heart failure, hypertension, valvular heart disease, or mitral walve prolapse suggests a strong link between wall motion abnormalities and arrhythmias. A potential common mechanism underlying these observations may be that overload leads to electrophysiologic changes and facilitates arrhythmias. This article summarizes the interaction between changes in atrial and ventricular loading conditions and repolarization. Most experimental and clinical studies demonstrated 1) a reduction of action potential duration and refractoriness, 2) development of early afterdepolarizations, and 3) ectopic beats originating from these afterdepolarizations. Discrepancies between studies are related to different study designs, i.e., varying magnitude, velocity, and timing of increased load, the level of repolarization at which action potential duration is measured as well as different animal species. Direct effects of increased load on repolarization are most likely caused by activation of stretch-activated nonselective cation ion channels and changes in calcium handling. Current antiarrhythmic drug therapy is aimed at electrical disorders as the primary cause of arrhythmias. If mechanical disorders play a central role in the genesis of cardiac arrhythmias, future treatment should be directed at restoring a more normal mechanical function of the heart. Additional studies will further clarify the nature and clinical significance of load-related changes in repolarization and arrhythmogenesis.

Clinical aspects of ventricular arrhythmias associated with QT prolongation

Abstract: QT interval prolongation is a risk factor in a number of cardiovascular as well as non-cardiovascular diseases. Apart from this, abnormal, i.e. excessive, QT prolongation is typical for patients with acquired as well as congenital long QT syndrome. In these syndromes, prolongation of repolarization is often associated with severe, potentially life-threatening, ventricular tachyarrhythmias of the type torsade de pointes (TdP). While the congenital long QT syndrome has recently been identified as an ion channelopathy, the mechanisms underlying acquired long QT syndrome, which is most often induced by drugs prolonging myocardial repolarization, are far from understood. Recent studies have yielded only a small number of individual cases in whom the clinical setting has suggested an acquired form of the syndrome and genetic analysis revealed a familial form. In order to prevent an unwanted exposure to risk, physicians prescribing agents that may prolong repolarization need to be aware of their potential to cause excessive QT prolongation and TdP. A clearer delineation of the factors predisposing to abnormal prolongation of repolarization and TdP, and a more precise quantification of the torsadogenic potency of individual drugs appear mandatory in order to prevent, or at least minimize, the incidence of this potentially fatal adverse effect of certain drugs.

Clinical value of electrocardiographic parameters in genotyped individuals with familial long QT syndrome.

Abstract: MOENNIG, G., et al.: Clinical Value of Electrocardiographic Parameters in Genotyped Individuals with Familial Long QT Syndrome. Rate corrected QT interval (QTc) and QT dispersion (QTd) have been suggested as markers of an increased propensity to arrhythmic events and efficacy of therapy in patients with long QT syndrome (LQTS). To evaluate whether QTc and QTd correlate to genetic status and clinical symptoms in LQTS patients and their relatives, ECGs of 116 genotyped individuals were analyzed. JTc and QTc were longest in symptomatic patients (n = 28). Both QTd and JTd were significantly higher in symptomatic patients than in asymptomatic (n = 29) or unaffected family members (n = 59). The product of QTd/JTd and QTc/JTc was significantly different among all three groups. Both dispersion and product put additional and independent power on identification of mutation carriers when adjusted for sex and age in a logistic regression analysis. Thus, symptomatic patients with LQTS show marked inhomogenity of repolarization in the surface ECG. QT dispersion and QT product might be helpful in finding LQTS mutation carriers and might serve as additional ECG tools to identify asymptomatic LQTS patients.

Prolonged QRS duration increases QT dispersion but does not relate to arrhythmias in survivors of acute myocardial infarction.

Abstract: QT dispersion has been suggested and disputed as a risk marker for ventricular arrhythmias after myocardial infarction. Delayed ventricular activation after myocardial infarction may affect arrhythmic risk and QT intervals. This study determined if delayed activation as assessed by (1) QRS duration in the 12-lead ECG and by (2) late potentials in the signal-averaged ECG affects QT dispersion and its ability to assess arrhythmic risk after myocardial infarction. QT duration, JT duration, QT dispersion, and JT dispersion were compared to QRS duration in the 12-lead ECG and to late potentials in the signal-averaged ECG recorded in 724 patients 2-3 weeks after myocardial infarction. Prolonged QRS duration (> 110 ms) and high QRS dispersion increased QT and JT dispersion by 12%-15% (P 0.2). In conclusion, prolonged QRS duration increases QT dispersion irrespective of arrhythmic events in survivors of myocardial infarction. Presence of late potentials, in contrast, relates to arrhythmic events but does not affect QT dispersion. Therefore, QT dispersion may not be an adequate parameter to assess arrhythmic risk in survivors of myocardial infarction.

Torsade de pointes induced by ajmaline.

Abstract: Ajmaline, a reserpine derivative, is an effective class I antiarrhythmic agent. Herein we report two cases of ajmaline-induced abnormal QT prolongation accompanied by polymorphic ventricular tachycardia of the torsade de pointes type. Since ajmaline is increasingly used for the acute termination of wide complex tachycardia and as a diagnostic tool after syncope and in patients with idiopathic ventricular tachyarrhythmias, our observations suggest that caution should be exercised with regard to the effects of the drug on the QT interval and its potency to induce proarrhythmia of the torsade de pointes type.

Genetic aspects in acquired long QT syndrome — a piece in the puzzle

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

In vivo recording of monophasic action potentials in awake dogs--new applications for experimental electrophysiology.

Abstract: Introduction Despite enormous developments in the field of clinical and experimental electrophysiology there is still a gap in evaluating repolarization in the awake animal. Numerous previous studies have used monophasic action potentials (MAP) to assess repolarization in vitro and in vivo in anesthetized animal models. However, an approach for recording MAP in awake dogs without interference of anesthesia has not yet been developed. Methods and results We developed an experimental technique to record MAP in conscious dogs by means of conventional rubber introducers which were implanted into the internal jugular vein. In seven awake dogs, atrial as well as ventricular MAP were simultaneously measured without complications. Pacing thresholds were low and stable over time ranging from 0.2 to 4.0 mA. The MAP amplitudes ranged from 10 to 30 mV for ventricular and from 5 to 15 mV for artial MAP. Contrinuous MAP recordings of stable amplitude could be made from the same endicardial site for periods of up to one hour. Antegrade and retrograde AV-nodal conduction properties could be assessed. Programmed stimulation was performed to simultaneously determine local refractory periods and MAP duration at cycle length from 500 to 200 ms. Conclusion In awake, unsedated dogs the measurement of MAP via rubber introducers permits safe, long-term recording of MAP. Such recordings may be useful for safety pharmacological studies in evaluating cardiovascular and non-cardiovascular drugs with regard to their effects on repolarization. In various canine in vivo models including in vivo models of long QT syndrome, heart failure or sudden cardiac death, the present technique permits electrophysiological measurements without interference of anesthesia.

Intracardiac tuberculoma causing "idiopathic" ventricular tachycardia in a patient without detectable heart disease.

Abstract: A 37-year-old man presented with frequent monomorphic ventricular tachycardia (VT; cycle length 340 msec, right bundle branch block morphology, superior axis, R-S interval . 80 msec) (panel A), with a second VT morphology inducible during electrophysiologic study (panel B). There was no clinical sign of infection or chronic disease. Results of echocardiography, right and left heart angiography, routine laboratory tests, and chest X-ray were normal. Antiarrhythmic drugs (beta blocker, sotalol 640 mg/day, and  ecainide alone or in combination) did not suppress VT inducibility or recurrence. Although extensive right and left ventricular endocardial mapping was performed, presystolic activity was not detected during VT. Earliest endocardial activation (5 msec before onset of QRS) was mapped to the left mid-lateral wall. Radiofrequency catheter ablation at this site was not successful, suggesting a nonendocardial VT origin. During open chest mapping, we identiŽ ed a left mid-lateral epicardial area with presystolic activation during VT (30 msec before onset of QRS) and fractionated electrograms during sinus rhythm. Applying pressure in this region terminated the VT. Palpation revealed a single nodular mass (1.3-cm diameter) in this area. Excising this mass suppressed VT inducibility. Histopathologic examination showed a nodule with granulomatous in ammation containing giant cells (panel C, arrows indicate granulomatous in ammation); polymerase chain reaction conŽ rmed presence of Mycobacterium tuberculosis. The patient died 4 days postoperatively, most likely due to tuberculous sepsis. “Idiopathic” VT may be the Ž rst clinical manifestation of tuberculosis. J Cardiovasc Electrophysiol, Vol. 12, p. 118, January 2001.

Simultaneous in utero assessment of AV nodal and ventricular electrophysiologic parameters in the fetal sheep heart.

Abstract: Background Fetal tachyarrhythmias are usually of supraventricular origin. To investigate whether specific electrophysiologic properties of the fetal heart contribute to this preponderance by either favoring supraventricular tachycardias or by rendering ventricular tachycardias unlikely, we measured fetal electrophysiologic parameters in utero using transuterine fetal transesophageal electrocardiograms in fetal sheep. Since overdrive pacing may help to establish the mechanism of an arrhythmia and may be used to treat fetal tachycardias, different modes of transesophageal pacing in utero were also assessed. Methods and results Decapolar electrophysiology catheters were fetoscopically inserted into the esophagus of 9 fetal sheep (pregnancy duration 94 – 105 days, term = 145 days). Electrocardiograms were recorded simultaneously from all adjacent bipoles and from two pacing wires sutured onto the fetal shoulders. Pacing was attempted either via two adjacent electrodes of the intraesophageal catheter or via the most distal and most proximal electrode.