Wolff-Parkinson-white syndrome: a genetic disease?
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AMP-Activated Protein Kinases↗
Biomedical subjects
H J Wellens
Publications and source records attributed to H J Wellens.
Chronic amiodarone evokes no torsade de pointes arrhythmias despite QT lengthening in an animal model of acquired long-QT syndrome.
BACKGROUND: Amiodarone is an effective antiarrhythmic drug rarely associated with torsade de pointes arrhythmias (TdP). The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired long-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment. METHODS AND RESULTS: Amiodarone (n=7, 40 mg. kg(-1). d(-1)) and dronedarone (n=8, 20 mg/kg BID) were started at 6 weeks of CAVB (baseline). Six dogs served as controls. Surface ECGs and endocardially placed monophasic action potential catheters in the left (LV) and right (RV) ventricles were recorded to assess QTc time, action potential duration (APD), interventricular dispersion (DeltaAPD=LV APD minus RV APD), early afterdepolarizations (EADs), ectopic beats, and TdP. Both amiodarone (+21%) and dronedarone (+31%) increased QTc time. Amiodarone showed no increase in DeltaAPD in 4 of 7 dogs, whereas dronedarone augmented DeltaAPD in 7 of 8 animals. After dronedarone, TdP occurred in 4 of 8 dogs with the highest DeltaAPD (105+/-20 ms). TdP was never seen with amiodarone, not even in the dogs that had DeltaAPD values comparable to those with dronedarone. Furthermore, a difference existed in EADs and ectopic activity incidence (dronedarone 3 of 8; amiodarone 0 of 7), which was also seen during an epinephrine challenge. CONCLUSIONS: In the CAVB dog model, both amiodarone and dronedarone prolong QT time (class III effect). The absence of TdP with amiodarone seems to be related to homogeneous APD lengthening in the majority of dogs and the lack of EADs and/or ventricular ectopic beats in all.
Action Potentials↗
Biatrial activation in isthmus-dependent atrial flutter.
BACKGROUND: The aim of this study was to determine the biatrial activation pattern in isthmus-dependent atrial flutter (AFL) to understand the functional interatrial connections and the activation pattern of the left atrium (LA). METHODS AND RESULTS: Biatrial activation was performed, using an electroanatomic mapping system, in 10 patients undergoing right atrial isthmus ablation for counterclockwise (n=7) or clockwise (n=3) AFL. The AFL circuit was peritricuspid and propagated slowly (0.5+/-0.2 m/s) through the isthmus. LA was activated by two wave fronts, with discrete breakthroughs in the superior, mid, or inferior atrial septum. The activation of LA overlapped 50+/-16% of the AFL cycle length. In counterclockwise AFL, at least one breakthrough was located in the inferior atrial septum. LA activation began immediately after the exit of the flutter wave from the isthmus and was directed inferosuperiorly in all patients, being synchronous with the atrial septal activation. The septal breakthroughs in patients with clockwise AFL were variably located. The direction of LA activation was superoinferior in 2 and inferosuperior in 1 patient. CONCLUSIONS: The circuit of isthmus-dependent AFL was entirely in the right atrium. LA activation was a bystander and followed trans-septal conduction across the inferior coronary sinus-LA connection, Bachmann's bundle, and/or fossa ovalis.
Atrial Flutter↗
Lead aVR, a mostly ignored but very valuable lead in clinical electrocardiography.
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Angina, Unstable↗
17beta-estradiol attenuates the development of pressure-overload hypertrophy.
BACKGROUND: Cardiac hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in men and in women. Epidemiological studies indicate that estrogen replacement therapy is cardioprotective; the mechanisms involved in this process, however, are poorly understood. We therefore studied the effect of 17beta-estradiol (E(2)) on the development of pressure-overload hypertrophy. METHODS AND RESULTS: Ovariectomized mice receiving E(2) or placebo underwent transverse aortic constriction (TAC) or sham operation. TAC led to a significant increase in ventricular mass compared with sham operation. E(2) treatment reduced cardiac hypertrophy by 31% and 26% compared with placebo 4 and 8 weeks after TAC, whereas it had no effect on the degree of pressure overload, as determined by hemodynamic measurements. Furthermore, E(2) blocked the increased phosphorylation of p38-mitogen-activated protein kinase (MAPK) observed in the placebo-treated animals with TAC. No differences were observed in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 between the groups. E(2) had no effect on the expression of angiotensin-converting enzyme (ACE) or the angiotensin II type 1 receptor. Ventricular atrial natriuretic peptide (ANP) expression was detected only in the animals with TAC. Compared with placebo, E(2) treatment led to an increased expression of ANP in animals with pressure overload. CONCLUSIONS: Here, we show that E(2) attenuates the hypertrophic response to pressure overload in mice. This observation demonstrates that hormone replacement therapy with E(2) has direct effects on the heart and may be beneficial in the treatment of postmenopausal women to reduce cardiac hypertrophy.
Animals↗
Usefulness of sinus tachycardia and ST-segment elevation in V(5) to identify impending left ventricular free wall rupture in inferior wall myocardial infarction.
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Aged↗
Azimilide and dofetilide produce similar electrophysiological and proarrhythmic effects in a canine model of Torsade de Pointes arrhythmias.
Torsade de Pointes arrhythmias are a feared proarrhythmic effect of (antiarrhythmic) drugs. In dogs with chronic complete AV-block bradycardia-induced volume overload leads to electrical remodeling, which includes increased susceptibility to drug-induced Torsade de Pointes arrhythmias. The IKr channel blocker, dofetilide (Tikosyn, 0.025 mg/kg/5 min), and the less specific ion channel blocker, azimilide (5 mg/kg/5 min), were compared in nine anesthetized dogs at 4 and 6 weeks of AV-block in a randomized cross-over design. Dosages were based on our own dose-dependence studies and on anti-arrhythmic dosages reported in the literature. Monophasic action potential catheters were placed endocardially in both the left and right ventricle to measure action potential duration, visualize early afterdepolarizations, and to assess interventricular dispersion of repolarization (i.e. left ventricular monophasic action potential duration (at 100%) minus right ventricular monophasic action potential duration (at 100%). Cycle length of idioventricular rhythm, QT-time and the occurrence of drug-induced Torsade de Pointes arrhythmias were determined using the surface electrocardiogram (ECG). Before drug administration, the electrophysiological parameters were identical at 4 and 6 weeks. Both azimilide and dofetilide increased monophasic action potential duration, cycle length of idioventricular rhythm, and QT-time. Dissimilar lengthening of left ventricular and right ventricular monophasic action potential duration increased the interventricular dispersion significantly from 55 to 110 ms for both drugs. All dogs had early afterdepolarizations, while, in the majority, ectopic ventricular beats developed (dofetilide 8/9 and azimilide 7/9). Torsade de Pointes arrhythmias incidence was comparable for dofetilide (6/9) and azimilide (5/9). In conclusion, azimilide and dofetilide show similar electrophysiological and proarrhythmic effects in our canine model with a high incidence of Torsade de Pointes arrhythmias.
Action Potentials↗
Electrophysiological parameters indicative of sudden cardiac death in the dog with chronic complete AV-block.
BACKGROUND: The dog model of chronic complete AV-block (CAVB) demonstrates a considerable incidence of (witnessed) sudden death (16/117 dogs). In this study we tried to: (1) elucidate the mechanisms of sudden death using an ECG telemetry device and (2) identify retrospectively the risk parameters indicative of this arrhythmogenic death. METHODS: Between 1994 and 1998, 78 anesthetized dogs underwent an extensive electrophysiological study including: (1) left- (LV) and right ventricular (RV) monophasic action potential (MAP) recordings to assess Delta MAPD (LV APD minus RV APD) and (2) pacing protocols (PES) to induce torsade de pointes arrhythmias (TdP) at 4--6 weeks CAVB. Eight animals experienced sudden cardiac death (SCD) during the follow-up period (mean 7+/-3 weeks CAVB). Since the response of the CAVB dog to class III drugs is not uniform we also made comparisons among the SCD group, TdP drug responders and non-responders. For this purpose we selected all animals which (1) received almokalant (n=15, 0.12 mg/kg/5 min) or ibutilide (n=9, 0.025 mg/kg/5 min) as an additional challenge to induce TdP and (2) had a follow-up period of at least 4 weeks. RESULTS: Six out of eight SCD dogs showed inducible TdP at baseline. Two of eight dogs had telemetric ECG surveillance and both revealed polymorphic VT as the cause of SCD. Baseline Delta MAPD of the SCD (90+/-15 ms) was significantly higher than the non-SCD group (n=70, 60+/-30 ms). Of the 24 dogs which received class III drugs, 12 belonged to the TdP responder group. Delta MAPD of the TdP responder group (80+/-15 ms) was similar to the SCD group and significantly higher compared to the non-responder group (n=12, 40+/-25 ms). QT-time and cycle length of idioventricular rhythm were not different. CONCLUSION: In the CAVB dog model, SCD is (1) most probably related to TdP while (2) inducible TdP and the measure of Delta MAPD at baseline indicate susceptibility to SCD.
Animals↗
The radiofrequency modified maze procedure. A less invasive surgical approach to atrial fibrillation during open-heart surgery.
OBJECTIVE: Patients with mitral valve disease and suffering of atrial fibrillation of more than 1 year's duration have a low probability of remaining in sinus rhythm after valve surgery alone. Intraoperative radiofrequency ablation was used as an alternative to simplify the surgical maze procedure. METHODS: Seventy-two patients with mitral valve disease, aged 63+/-11 years ranging from 31 to 80 years, underwent valve surgery and radiofrequency energy applied endocardially, based on the maze III procedure to eliminate the arrhythmia. The right-sided maze was performed on the beating heart and the left-sided maze during aorta cross-clamping. RESULTS: Surgical procedures included mitral valve repair (n=38) or replacement (n=34) and in addition tricuspid valve repair (n=42), closure of an atrial septal defect (n=2) and correction of cor triatriatum (n=1). The left-sided maze needed 14+/-3 min extra ischemic time. There were two in-hospital deaths (2.7%) and three patients (4.2%) died during follow-up of 20+/-15 months. Among 67 surviving patients, 51 patients (76%) were in sinus rhythm, two patients (3%) had an atrial rhythm and eight patients (12%) had persistent atrial fibrillation or atrial flutter. Four patients had a pacemaker implanted, in one patient because of sinus node dysfunction. Doppler echocardiography in 64 patients demonstrated right atrial contractility in 89% and left atrial transport in 91% of patients. CONCLUSIONS: Intraoperative radiofrequency ablation of atrial fibrillation is an effective and less invasive alternative for the original maze procedure to eliminate atrial fibrillation.
Adult↗
Interactions between pacing and arrhythmia detection algorithms in the dual chamber implantable cardioverter defibrillator.
Dual chamber implantable cardioverter defibrillator (ICD) combines the possibility to detect and treat ventricular and atrial arrhythmias with the possibility of modern heart stimulation techniques. Advanced pacing algorithms together with extended arrhythmia detection capabilities can give rise to new types of device-device interactions. Some of the possible interactions are illustrated by four cases documented in four models of dual chamber ICDs. Functioning of new features in dual chamber devices is influenced by the fact that the pacemaker is not a separate device but a part of the ICD system and that both are being used in a patient with arrhythmia. Programming measures are suggested to optimize use of new pacing algorithms while maintaining correct arrhythmia detection.
Adult↗
Merits and limitations of the mode switching rate stabilization pacing algorithms in the implantable cardioverter defibrillator.
BACKGROUND: The 7250 Jewel AF Medtronic model of ICD is the first implantable device in which both therapies for atrial arrhythmias and pacing algorithms for atrial arrhythmia prevention are available. Feasibility of that extensive atrial arrhythmia management requires correct and synergic functioning of different algorithms to control arrhythmias. METHODS AND RESULTS: The ability of the new pacing algorithms to stabilize the atrial rate following termination of treated atrial arrhythmias was evaluated in the marker channel registration of 600 spontaneously occurring episodes in 15 patients with the Jewel AF. All patients (55+/-15 years) had structural heart disease and documented atrial and ventricular arrhythmias. Dual chamber rate stabilization pacing was present in 245 (41 %) of episodes following arrhythmia termination and was a part of the mode switching operation during which pacing was provided in the dynamic DDI mode. This algorithm could function as the atrial rate stabilization pacing only when there was a slow spontaneous atrial rhythm or in presence of atrial premature beats conducted to the ventricles with a normal AV time. In case of atrial premature beats with delayed or absent conduction to the ventricles and in case of ventricular premature beats, the algorithm stabilized the ventricular rate. The rate stabilization pacing in DDI mode during sinus rhythm following atrial arrhythmia termination was often extended in time due to the device-based definition of arrhythmia termination. This was also the case in patients, in whom the DDD mode with true atrial rate stabilization algorithm was programmed. CONCLUSIONS: The rate stabilization algorithms in the Jewel AF applied after atrial arrhythmia termination provide pacing that is not based on the timing of atrial events. Only under certain circumstances the algorithm can function as atrial rate stabilization pacing. Adjustments in availability and functioning of the rate stabilization algorithms might be of benefit for the clinical performance of pacing as part of device therapy for atrial arrhythmias.
Adult↗
Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart.
We report a novel real-time imaging model to visualize apoptotic membrane changes of single cardiomyocytes in the injured heart of the living mouse, using fluorescent labeled annexin-V. Annexin-V binds to externalized phosphatidylserine (PS) of cells undergoing programmed cell death. With high-magnification (x100-160) real-time imaging, we visualized the binding of annexin-V to single cardiomyocytes. Kinetic studies at the single-cell level revealed that cardiomyocytes started to bind annexin-V within minutes after reperfusion, following an ischemic period of 30 minutes. The amount of bound annexin-V increased rapidly and reached a maximum within 20-25 minutes. Caspase inhibitors decreased the number of annexin-V-positive cardiomyocytes and slowed down the rate of PS exposure of cardiomyocytes that still bound annexin-V. This technology to study cell biology in the natural environment will enhance knowledge of intracellular signaling pathways relevant for cell-death regulation and strategies to manipulate these pathways for therapeutic effect.
Animals↗
Use of a saline-irrigated tip catheter for ablation of ventricular tachycardia resistant to conventional radiofrequency ablation: early experience.
INTRODUCTION: Radiofrequency (RF) catheter ablation of ventricular tachycardia (VT) may fail if the critical isthmus is located intramyocardially or epicardially. The design of a saline-irrigated tip (SIT) catheter (Thermo-Cool, Cordis-Webster) involves active cooling of the tip electrode, which allows creation of larger ablation lesions. METHODS AND RESULTS: Eight patients (6 men, age 59 +/- 12 years) in whom the clinical target VT (cycle length 430 +/- 97 msec) could not be ablated using a conventional 4-mm tip RF ablation catheter underwent additional attempts to ablate this VT using a SIT catheter. Six patients had an old myocardial infarction, 1 patient had a dilated cardiomyopathy, and 1 patient had a structurally normal heart. Ablation of the clinical target VT using a SIT catheter was attempted from the left ventricle in 6 (septal, posterobasal, and inferior: 2 each) and from the right ventricle in 2 patients (both septal), by entrainment (n = 6), activation (n = 1), or pace mapping (n = 1). A mean of 6 +/- 5 (range 2 to 15) pulses were delivered. Target VT ablation was successful in 5 patients (63%). After successful ablation, at a mean follow-up of 6.5 +/- 4 months and while taking antiarrhythmic drugs, all 5 patients were free of VT recurrences. CONCLUSION: The clinical target VT could be ablated using a SIT catheter in 5 (63%) of the 8 patients in whom ablation using a conventional RF catheter was unsuccessful. In the 2 patients with septal VT, a biventricular approach to mapping and ablation was required.
Adult↗
Task Force on Sudden Cardiac Death of the European Society of Cardiology.
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Algorithms↗
Radiofrequency modified maze in patients with atrial fibrillation undergoing concomitant cardiac surgery.
OBJECTIVE: In the majority of patients with chronic atrial fibrillation the arrhythmia will persist after correction of the underlying structural abnormality. The maze procedure is an effective surgical method to eliminate atrial fibrillation and to restore atrial contractility. METHODS: In this study we used radiofrequency energy to create lines of conduction block in both atria during cardiac surgery as a modification of the maze III procedure. One hundred twenty-two patients with atrial fibrillation for at least 1 year and structural heart disease underwent open heart operation and a radiofrequency modified maze procedure. RESULTS: In 108 (89%) of 122 patients mitral valve surgery was performed, and in this group 86 patients (80%) underwent 121 concomitant procedures. Fourteen patients (11%) underwent cardiac surgery not involving the mitral valve. The additional crossclamp time required for the left atrial part of the radiofrequency modified maze procedure was 14 +/- 3 minutes. The in-hospital mortality rate was 4.1%. The overall 39-month survival was 90%, and freedom of atrial flutter or atrial fibrillation was 78.5% +/- 5.1%. Eighty-nine survivors with sinus, atrial rhythm, or atrioventricular sequential pacemaker had Doppler echocardiography, and right atrial transport function was documented in 83% and left atrial transport function in 77% of patients. CONCLUSION: We concluded that the radiofrequency modified maze procedure as an adjunctive procedure is safe, time-sparing, and effective in eliminating atrial fibrillation and restoring atrial transport function.
Aged↗
Class IC antiarrhythmic drug induced atrial flutter: electrocardiographic and electrophysiological findings and their importance for long term outcome after right atrial isthmus ablation.
OBJECTIVE: To describe the electrocardiographic and electrophysiological findings of new atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation, and to report the long term results of right atrial isthmus ablation in relation to the ECG pattern of spontaneous atrial flutter. DESIGN: Retrospective analysis. SETTING: Tertiary care academic hospital. PATIENTS: 24 consecutive patients with atrial fibrillation (age 54 (12) years; 5 female, 19 male) developing atrial flutter while taking propafenone (n = 12) or flecainide (n = 12). RESULTS: The ECG was classified as typical (n = 13; 54%) or atypical atrial flutter (n = 8) or coarse atrial fibrillation (n = 3). Counterclockwise atrial flutter was the predominant arrhythmia. Acute success after isthmus ablation was similar in patients with typical (12/13) and atypical (8/8) atrial flutter. After long term follow up (13 (6) months, range 6-26 months), continuation of antiarrhythmic drug treatment appeared to result in better control of recurrences of atrial fibrillation in patients with typical atrial flutter (11/13) than in those with atypical atrial flutter (4/8), but the difference was not significant. Ablation for coarse atrial fibrillation was unsuccessful. CONCLUSIONS: New atrial flutter developing in patients taking class IC antiarrhythmic drugs for recurrent atrial fibrillation has either typical or atypical flutter wave morphology on ECG. The endocardial activation pattern and the acute results of ablation suggest that the flutter circuit was located in the right atrium and that the isthmus was involved in the re-entry mechanism. There appeared to be better long term control of recurrent atrial fibrillation in patients with typical (85%) as compared with atypical atrial flutter (50%). Patients developing coarse atrial fibrillation may not be candidates for this strategy.
Adult↗
Electrophysiology: Ventricular tachycardia: diagnosis of broad QRS complex tachycardia.
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Diagnosis, Differential↗
Time course of structural adaptations in chronic AV block dogs: evidence for differential ventricular remodeling.
To determine the nature and time course of biventricular hypertrophy and concomitant electrical and mechanical changes after creation of complete atrioventricular block (CAVB), six adult dogs (22-30 kg) were subjected to serial magnetic resonance imaging (MRI) and electrocardiography. After 6 days of CAVB, left ventricular (LV) mass, ejection fraction (EF), and Q-T time at a paced rhythm of 60 beats/min were already significantly increased. Maximal values were reached within 14-21 days of CAVB: LV mass, from 116 +/- 11 to 143 +/- 12 g; right ventricular (RV) mass, from 40 +/- 3 to 55 +/- 6 g; EF, from 68 +/- 6% to 86 +/- 5%; and Q-T time, from 285 +/- 25 to 330 +/- 35 ms, all P < 0.05. Cardiac output returned to baseline at day 14. End-diastolic wall thickness increased only in the RV, in which angiotensin type 1 (AT1) receptor mRNA expression was significantly greater. The autopsy correlated well with the MRI results (r = 0.98, P< or = 0.01). In conclusion, electrophysiological, mechanical, and structural adaptation processes after bradycardia-induced volume overload develop rapidly and are completed within 3 wk. The degree of hypertrophy was greater in the RV, which was associated with an increase in AT1 receptor mRNA.
Animals↗