Bundle Electrography Research Articles

Historical development of diagnosis of bradyarrhythmias : The early years of clinical electrophysiology in Germany

The introduction of His bundle electrography by Benjamin Scherlag (New York) in 1969, together with programmed stimulation of the heart by Philip Coumel (Paris) in 1967, and Hein Wellens (Amsterdam) in 1972, were decisive turning points on the way to invasive electrophysiology and the development of an independent, now distinctly interventional subspecialty of cardiology. The main topic of the 1970s was bradycardic arrhythmias, promoted by pacemaker therapy, which had been introduced just over 10years earlier. The recording of the potentials of the bundle of His and other recording locations in the atria and ventricles allowed adifferentiated assessment of the excitation process and the refractory periods. High-rate atrial stimulation to determine sinus node recovery time and premature stimulation to determine sinoatrial conduction time were developed to analyze sinoatrial node function. This article describes the introduction of His bundle electrography in agradually increasing number of centers in Germany and their scientific contribution.

History of catheter ablation

After His bundle electrography was established in 1967, the step from invasive electrophysiologic diagnosis of arrhythmias to interventional treatment by catheter ablation was imminent. The time interval of 15 years between the diagnosis and treatment of arrhythmias was even shorter than the 19 years between the first selective coronary angiography in 1958 at the Cleveland Clinic in the USA and the first percutaneous coronary intervention in 1977 in Zurich. During each time period, a great amount of knowledge was gained in cardiac surgery, which proved to be very helpful for the development of the interventional treatment. The history of endovascular treatment is an impressive reminder that the preparation and support of cardiovascular surgeons and their handling of complications played a decisive role in the further development of cardiovascular internal medicine. The history of catheter ablation teaches us that the joint work of cardiologists and cardiovascular surgeons is of great importance for the choice and further development of the best possible treatment as for future development of the techniques of therapy.

The 125th anniversary of the His bundle discovery.

In 1893, Wilhelm His Jr. was the first to describe the AV (atrioventricular) bundle of the vertebrate heart, which now bears his name. Moreover, prior to the turn of the century, W.His Jr. had proved the function of the AV bundle by transection experiments in animals, and had interpreted Adams Stokes disease as heart block due to pathological changes within the bundle. In this way, he was ahead of his time. While clinical interest was limited to the bundle as the location of an AV block in the first half of the 125years, it has gained attractiveness since then as atarget of diagnostic and therapeutic procedures. The introduction of His bundle electrography relaunched the interest in cardiac arrhythmias. Once the AV bundle could be localized clinically, its ablation, and in recent times its permanent stimulation, became options in the therapy of well-defined arrhythmia and conduction problems.

Cardiac asystole during a cluster of right temporo-parietal seizures

Ictal bradycardia and asystole can appear during an epileptic seizure. They must be promptly recognized and treated due to their potential life threatening consequences. Indeed, they have been implicated in the pathogenesis of sudden unexpected death in epilepsy (SUDEP). We report the case of a 33 year-old woman with a right temporo-parietal lobe epilepsy who presented a 19 s asystole during a cluster of seizures. Careful interview revealed appearance of numerous episodes of fall in the previous years. The patient underwent cardiological investigations including echocardiography and His bundle electrography that resulted to be normal. A pacemaker was immediately implanted and, although she continued presenting seizures, no more episodes of falls occurred. In order to better preview ictal asystole several risk factors need to be searched. Attention should be paid to an accurate medical history (ask for episodes of falls) and a simultaneous ECG/EEG recording. The occurrence of bradycardia during a seizure should lead to further cardiological investigations. This could help preventing the occurrence of dramatic consequences such as traumatic falls or SUDEP.

Diagnosis and treatment of catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (VT) was first described by Reid et al 1 Reid D.S. Tynan M. Braidwood L. Fitzgerald G.R. Bidirectional tachycardia in a child A study using His bundle electrography. Br Heart J. 1975; 37: 339-344 Crossref PubMed Scopus (138) Google Scholar in 1975 and by Coumel et al in 1978. The condition was described as a familial cardiac arrhythmia that occurs in patients with structurally normal heart and causes exercise-/emotion-triggered syncope and sudden death with a distinctive pattern of ventricular and supraventricular arrhythmias. Since the first ryanodine receptor mutations were identified in 2001, 2 Priori S.G. Napolitano C. Tiso N. Memmi M. Vignati G. Bloise R. Sorrentino V. Danieli G.A. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation. 2001; 103: 196-200 Crossref PubMed Scopus (1135) Google Scholar it appeared evident that catecholaminergic polymorphic VT was caused by uncontrolled Ca2+ release from the sarcoplasmic reticulum. 3 Jiang D. Xiao B. Yang D. Wang R. Choi P. Zhang L. Cheng H. Chen S.R. RyR2 mutations linked to ventricular tachycardia and sudden death reduce the threshold for store-overload-induced Ca2+ release (SOICR). Proc Natl Acad Sci U S A. 2004; 101: 13062-13067 Crossref PubMed Scopus (350) Google Scholar Subsequent experimental studies demonstrated that such abnormal calcium handling caused arrhythmias mediated by delayed afterdepolarizations and triggered activity. 4 Liu N. Colombi B. Memmi M. Zissimopoulos S. Rizzi N. Negri S. Imbriani M. Napolitano C. Lai F.A. Priori S.G. Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia Insights from a RyR2 R4496C knock-in mouse model. Circ Res. 2006; 99: 292-298 Crossref PubMed Scopus (261) Google Scholar This article reviews the current knowledge of the diagnosis and therapy for catecholaminergic polymorphic VT and outlines the open issues to be addressed in order to reduce the burden of life-threatening cardiac events in patients with this lethal disorder.

Management of Stokes-Adams Syndrome

Stokes-Adams attacks are related to paroxysmal or chronic atrioventricular (AV) block (50-60%), sinoatrial (SA) block (30-40%) or paroxysmal tachycardia or fibrillation (0-5%). In between attacks most patients present with sinus rhythm, a large part with widened QRS complex. A minor proportion of patients present with chronic AV block. ECG is very rarely normal. Diagnosis is based on ECG recording during fainting. In patients with sinus rhythm and bundle-branch block or AV block, ECG monitoring should be performed in hospital, since Stokes-Adams syndrome in these patients is a potentially life-threatening disease. In sick sinus syndrome where the suspected arrhythmia is not life-threatening, ambulatory ECG by Holter monitoring can be performed to establish the diagnosis. In cases where ECG monitoring leaves doubt, an electrophysiologic study including His bundle electrography and sinus node recovery time may support the diagnosis, although normal findings do not preclude the diagnosis. Pacemaker implantation should be performed in Stokes-Adams syndrome, as oral drug treatment is ineffective. The dual-chamber pacemaker presents the advantages of both physiological heart rate and AV synchrony, but has troublesome side effects. Most patients with tachycardia/bradycardia syndromes require supplementary anti-arrhythmic treatment, and in some patients additional long-term anticoagulation should be considered.

Acute electrophysiologic and blood pressure effects of amiodarone and its solvent in the dog.

Amiodarone has repeatedly been shown to have potent class III antiarrhythmic properties. It has, however, been questioned whether the acute and chronic effects of the drug are due to the same mechanism. In order to investigate the acute electrophysiologic and blood pressure effect of the drug, amiodarone (Cordarone) was given intravenously in cumulative doses of 2.5, 5.0 and 10.0 mg/kg to seven pentobarbital (mebumalum NFN) anaesthetized dogs. Corresponding volumes of the solvent, polysorbatum 80 (Tween 80), were given to two dogs. Cardiac electrophysiologic effects were studied by His bundle electrography and programmed electrical stimulation. Amiodarone decreased heart rate and AV nodal conduction velocity and increased atrial, AV nodal and ventricular refractoriness. A pronounced but transient fall in mean aortic blood pressure (MABP) occurred after the first injection of amiodarone. No fall in MABP occurred, however, after the subsequent two doses. Intravenous injection of the solvent exactly reproduced the effects on MABP, but not the electrophysiologic effects. The present study supports the concept that amiodarone also has acute class III antiarrhythmic effect. After the initial injection, a pronounced fall in blood pressure due to the solvent may be seen, but rapid tachyphylaxis occurs.

Cardiac effects of thoracic epidural morphine caused by increased vagal activity in the dog.

This study was carried out in order to investigate possible side-effects of thoracic epidural morphine on cardiac electrophysiology, haemodynamics and metabolism. In pentobarbital-anaesthetized dogs, intracardiac conduction times were determined by His bundle electrography, and refractoriness by programmed electrical stimulation; monophasic action potential recordings were obtained from the right ventricle by the suction electrode technique. Cardiac output, left ventricular and aortic blood pressures were measured, as well as plasma concentrations of morphine, free fatty acids, glycerol, glucose and lactate. Thoracic epidural morphine (0.12 mg X kg-1) reduced spontaneous heart rate, prolonged atrioventricular nodal conduction time and refractoriness, and reduced left ventricular dP/dt max. Bilateral vagotomy reversed these effects. Intra-atrial, His Purkinje and intraventricular conduction times, atrial and ventricular refractoriness and action potential duration, stroke volume and mean aortic blood pressure, as well as the metabolic variables, were not significantly influenced by thoracic epidural morphine with or without vagotomy. Peak plasma morphine levels of 12-25 ng X ml-1 were measured 10 min after morphine injection. In conclusion, this study demonstrates depressive side-effects of epidural morphine on cardiac function, mediated by an increased vagal activity.

Cardiac Electrophysiologic and Hemodynamic Effects Related to Plasma Levels of Bupivacaine in the Dog

To investigate electrophysiologic and hemodynamic responses to various plasma levels of bupivacaine, especially those in the range normally seen during regional anesthesia, bupivacaine was given intravenously as a bolus dose followed by continuous infusion in pentobarbital-anesthetized dogs. Cardiac electrophysiology was studied by His bundle electrography, programmed electrical stimulation, and monophasic action potential recordings. At plasma bupivacaine concentrations below 1000 ng/ml, no significant electrophysiologic or hernodynamic effects mere observed. This indicates that systemic responses to absorbed bupivacaine do not contribute to the cardiac electrophysiologic effects recently demonstrated during thoracic epidural analgesia. At a plasma level of about 2000 ng/ml, a level occasionally achieved during regional anesthesia, bupivacaine prolonged impulse conduction time in all parts of the heart, prolonged atrial and AV nodal refractoriness, decreased left ventricular inotropy, but had no effect on ventricular refractoriness or monophasic action potential duration. These electrophysiologic effects may enhance susceptibility to reentrant arrhythmias.

Correlates of prolonged HV conduction in aortic stenosis

Forty-eight patients with predominant aortic stenosis underwent His bundle electrography (HBE) at the time of diagnostic catheterization. Patients were divided into four groups based upon severity of calcification of the aortic valve fluoroscopically as judged independently by three angiographers. Of 48 patients, three had no calcification, 11 had mild, 18 had moderate, and 16 had severe aortic valve calcification. No correlation was found between HV interval and severity of aortic valve calcification. Significant correlation was found between HV interval prolongation and aortic valve area ( p < 0.02), history of congestive heart failure ( p < 0.02), and increasing left ventricular end-diastolic pressure ( p < 0.05). Left ventricular ejection fraction <45% had greater likelihood of HV interval prolongation ( p < 0.01). No correlation was established between HV interval and age, aortic valve gradient, left ventricular peak systolic pressure, syncope, and coronary artery disease. Aortic valve area was the most significant independent predictor of HV prolongation, with history of congestive heart failure second. We conclude that HV interval prolongation in aortic stenosis with calcified valves is best predicted by evidence of declining left ventricular function rather than severity of aortic valve calcification.

Cardiac Electrophysiologic and Hemodynamic Effects Related to Plasma Levels of Bupivacaine in the Dog

To investigate electrophysiologic and hemodynamic responses to various plasma levels of bupivacaine, especially those in the range normally seen during regional anesthesia, bupivacaine was given intravenously as a bolus dose followed by continuous infusion in pentobarbital-anesthetized dogs. Cardiac electrophysiology was studied by His bundle electrography, programmed electrical stimulation, and monophasic action potential recordings. At plasma bupivacaine concentrations below 1000 ng/ml, no significant electrophysiologic or hemodynamic effects were observed. This indicates that systemic responses to absorbed bupivacaine do not contribute to the cardiac electrophysiologic effects recently demonstrated during thoracic epidural analgesia. At a plasma level of about 2000 ng/ml, a level occasionally achieved during regional anesthesia, bupivacaine prolonged impulse conduction time in all parts of the heart, prolonged atrial and AV nodal refractoriness, decreased left ventricular inotropy, but had no effect on ventricular refractoriness or monophasic action potential duration. These electrophysiologic effects may enhance susceptibility to reentrant arrhythmias.

Cardiac Electrophysiological and Hemodynamic Effects of jS-Adrenoceptor Blockade and Thoracic Epidural Analgesia in the Dog

To investigate whether thoracic epidural analgesia (TEA) has additional cardiac electrophysiological and hemodynamic effects when induced after beta-adrenergic blockade, bupivacaine (0.7-1.2 mg/kg) was injected into the epidural space at T2-3 after intravenous injection of atenolol (1.0 mg/kg) in anesthetized dogs. Cardiac electrophysiology was studied by His bundle electrography, programmed electrical stimulation, and monophasic action potential recordings. Atenolol reduced heart rate, prolonged atrio-ventricular (AV) nodal impulse conduction time and refractoriness, prolonged ventricular refractoriness and action potential duration, and decreased left ventricular (LV) dP/dt max. Addition of TEA further reduced heart rate, prolonged AV nodal conduction time and refractoriness, decreased LV dP/dt max and arterial blood pressure, but had no effect on atrial and ventricular electrophysiology. Induction of TEA during beta-blockade may thus have additive depressive effects on sinoatrial and AV nodal functions, as well as on left ventricular inotropy. The study indicates that the cardiac electrophysiological effects induced by TEA are mainly caused by decreased beta-receptor stimulation, but increased vagal activity may also contribute.

Electrophysiological effects of quinidine alone and of the combination quinidine-verapamil on AV conduction in humans.

The influence of 320 mg quinidine administered intravenously (i.v.), as well as subsequent administration of 5 mg verapamil i.v. on atrioventricular conduction was studied in 8 patients during sinus rhythm and atrial stimulation with the aid of His bundle electrography. Among the electrophysiologic parameters of the atrium the sinus rate increased significantly after quinidine and again increased slightly after subsequent administration of verapamil. During sinus rhythm the PA interval was not influenced by either substance. Conversely, during atrial stimulation the STA interval increased significantly under the effect of quinidine, while verapamil had no further influence. As an indicator of conduction time in the AV node, the AH interval was decreased significantly by quinidine during sinus rhythm and atrial stimulation. This effect was significantly counteracted by the additional administration of verapamil. The HV interval as a measure of the His-Purkinje conduction was not significantly affected. The QRS duration was increased significantly by quinidine and was not further influenced by verapamil. The QTc and QT intervals increased significantly after administration of quinidine and were again slightly, but significantly shortened by verapamil. Our investigations show that the combination of quinidine and verapamil, which has clinically been found to have a higher conversion rate than quinidine alone, is well justified from an electrophysiologic point of view and that undesirable quinidine-related effects, such as rapid AV conduction in cases of atrial fibrillation and flutter, can be avoided by the subsequent administration of verapamil.

Electrophysiological effects of thoracic epidural analgesia in the dog heart in situ.

To investigate cardiac electrophysiological effects of thoracic epidural analgesia, a local anaesthetic solution, 0.5% bupivacaine, was administered into the thoracic epidural space in twelve pentobarbital anaesthetised dogs. Intracardiac conduction times were measured by His bundle electrography and refractoriness was determined by programmed electrical stimulation. Monophasic action potentials were recorded from the right ventricle by a suction electrode technique. Thoracic epidural analgesia increased the ventricular effective and functional refractory period, as well as the duration of the monophasic action potential. The intra-atrial and His-Purkinje conduction times and the QRS-width were not significantly influenced. AV nodal conduction time and AV nodal functional refractory period were markedly prolonged by thoracic epidural analgesia. Thoracic epidural analgesia induced AV block of the second degree in most experiments after a second dose of bupivacaine during pacing at higher frequencies. We conclude that thoracic epidural analgesia has significant cardiac electrophysiological effects which may be both antiarrhythmic and arrhythmogenic. Thoracic epidural analgesia should be used with care in patients with atrioventricular conduction disturbances.

Wenckebach phenomenon (W.P.) at sites other than A-V junctional area.

W.P. occurring at sites other than A-V junctional area are reported. Some of the cases are rather rare. His bundle electrography may be the best method in discovering the site of block, but the using of conventional ECG is also able to detect a correct diagnosis. Clinical significance are discussed, some are innocent, some are related to serious heart disease. Thorough examination is necessary before arriving at any conclusion.

Pentobarbital plasma concentrations and cardiac electrophysiology during prolonged pentobarbital infusion anaesthesia in the dog.

There is need for a prolonged stable level of anaesthesia, and we therefore investigated the cardiac electrophysiological effects of continuous pentobarbital infusion after initial pentobarbital injection to induce anaesthesia in dogs. Plasma concentrations of pentobarbital were measured by gas-liquid chromatography. Heart rate, atrial, atrioventricular (AV) nodal and His-Purkinje conduction times were measured by His bundle electrography, and atrial, AV nodal and ventricular refractoriness by programmed electrical stimulation. Over a 5-h observation period, continuous infusion of pentobarbital 3.5 mg X kg-1 X h-1 after an initial pentobarbital injection of 25 mg X kg-1 intravenously gave stable mean plasma concentrations of 140-135 mumol X 1(-1). The cardiac electrophysiological variables studied did not change significantly during this period. We conclude that a stable experimental model for cardiac electrophysiological studies can be obtained for several hours by continuous pentobarbital infusion.

Noninvasive Recording of His‐Purkinje System (HPS) Activity in Man on Beat‐To‐Beat Basis

Since 1969 His bundle electrography has been used for diagnosis and for the study of cardiac electrophysiology. This method has employed the catheterization technique and has allowed the continuous recording of electrical activity of the specialized cardiac conduction system in every beat. Such investigation, because of its invasive nature, cannot be considered a routine test; it requires expensive instrumentation, it has physiological and technical limitations that include discomfort, a slight morbidity risk and a rather limited recorded area within the heart. In 1973 a method was developed for a noninvasive recording of the electrical activity within the P-R segment of the electrocardiogram measured from the body surface. This method which employs the signal averaging technique delivers even less medical information than intracardiac measurement. The shortcomings of this averaging method include inability to detect beat-to-beat changes in the true signal. Such a method is not useful in transient arrhythmia detection and a "short acting" drug influence examination. The technical approach to the beat-to-beat noninvasive recording of the HPS activation signal as measured from the body surface has been proposed. Using a specially positioned electrode system, a low noise multiple parallel input amplifier and a computer for sampling, processing and plotting of the measured signal, we have obtained an output curve corresponding to the continuous beat-to-beat HPS activity.

Electrophysiological effects of lorcainide in sinoatrial disease and in Wolff-Parkinson-White syndrome.

The influence of lorcainide on sinus node function and intracardiac conduction was studied in 34 patients, including seven patients with sinoatrial disease and 14 patients with Wolff-Parkinson-White syndrome. Programmed cardiac stimulation and His bundle electrography were undertaken. Lorcainide, 2 mg/kg body weight, was given intravenously over a period of 10 min. In normal subjects, a slight increase of sinus rate was observed; lorcainide did not change corrected sinus node recovery time (CSNRT) and sinoatrial conduction time (SACT), calculated by use of the premature stimulus technique. In sinoatrial disease, however, three out of seven patients demon-strated a decrease of heart rate due to sinus node exit block, and CSNRT was markedly prolonged under the influence of the drug. Sinus node entrance block to premature atrial beats was observed in two controls and two patients with sinoatrial disease. Spontaneous sinus node exit block developed in two patients with sinoatrial dysfunction after administration of lorcainide. Refractory periods of the right atrium, right ventricle and conduction through the A V node (AH intervals) were unaffected by lorcainide, while HQ, QRS and QT intervals were prolonged. In Wolff-Parkinson-White syndrome, antegrade conduction via the accessory pathway was blocked in six out of 12 patients. After lorcainide, refractory periods of the accessory pathway increased in both the antegrade and retrograde direction. The ventricular rate during reciprocating tachycardia and during atrial fibril-lation was decreased by lorcainide. The results identify slowing of intraventricular conduction as the main action oflorcainide. In sinoatrial disease, lorcainide may aggravate sinus node dysfunction.

The mode of antiarrhythmic action of melperone.

We studied the mode of antiarrhythmic action of melperone by His bundle electrography combined with programmed electrical stimulation in 21 pentobarbital anaesthetized dogs. Melperone alone (0.5 to 12.5 mg/kg) as well as melperone after sympathetic and parasympathetic blockade caused a dose-dependent increase in the ventricular and, even more, the atrial effective refractory period without affecting atrial and ventricular conduction times. Melperone shortened the atrioventricular nodal conduction time regardless of sympathetic and parasympathetic blockade. We conclude that the antiarrhythmic effect of melperone in most likely primarily due to a direct class III antiarrhythmic action.

Free fatty acids and the electrophysiology of the dog heart in situ: effects of isoprenaline, nicotinic acid and lipid emulsion with heparin

Summary. The study was carried out to examine whether high plasma concentrations of free fatty acids (FFA) alone have cardiac electrophysiological effects, and whether the electrophysiological effects of isoprenaline are dependent on elevated plasma FFA. Experiments were performed in sixteen intact, healthy, pentobarbital anaesthetized dogs. Atrial, atrioventricular nodal and ventricular conduction times and refractoriness, and sinus node function were studied by His bundle electrography combined with programmed electrical stimulation. Elevation of plasma FFA by Intralipid and heparin from a median value of 363 to 1780 u‐moM‐1 did not induce any changes in cardiac electrophysiology. Intravenous infusion of isoprenaline (0.15 μg‐min_1‐kg‐1) increased median plasma FFA from 410 to 2254 μmol‐l‐1. This rise in plasma FFA could be prevented by administration of nicotinic acid. The electrophysiological effects of isoprenaline were similar before and after inhibition of lipolysis. The study indicates that the cardiac electrophysiological effects of isoprenaline in the intact, healthy heart are independent of changes in plasma FFA concentrations.