Table of Contents
Significant Events in the 1980s:
- 1980: John Lennon assassinated
- 1981: Fifty-two U.S. diplomats held hostage in Tehran released
- 1981: The IBM personal computer with Microsoft software is introduced
- 1981: Acquired Immunodeficiency Syndrome Disease (AIDS) appears
- 1981: First woman appointed to the United States Supreme Court
- 1989: The Berlin Wall falls, Germany is reunited
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Demonstration of the 3rd Criterion of Entrainment:
Interruption of a tachycardia (in this case, ventricular tachycardia) during rapid (overdrive) pacing at a constant rate associated with localized conduction block to a site or sites for one beat followed by activation of that site or sites from a different direction and with a shorter conduction time.
…Leads I and V1 recorded simultaneously with the atrial pacing stimulus (S) artifact (Stim), and the unipolar ventricular electrogram (Veg) during atrial pacing at a rate of 165 beats/min (364 ms cycle length). The circled stars denote an abrupt change in configuration of the recorded QRS complexes in both leads and in the unipolar ventricular electrographic complex. In the ventricular electrographic tracing, each arrow points to the resulting ventricular electrogram. Before the change in configuration of the QRS complex and ventricular electrogram, the stimulus to ventricular electrogram interval is 640 ms. Then, after the localized block to the ventricular electrographic recording site, the stimulus to ventricular electrogram interval become 305 ms. Note also that this localized conduction block is associated with a one cycle increase in the beat to beat cycle length localized to the ventricular electrographic recording site (from 364 to 425 and then back to 364 ms). In the lead 1 tracing, the dashed arrows represent the antidromic wavefronts from the 5th and 6th pacing impulses. After the block of both the antidromic and the orthodromic impulsed of the 6th pacing impulse in the reentrant loop of the ventricular tachycardia, the ventricles are activated by the 7th pacing impulse, as expected, during overdrive atrial pacing of a sinus rhythm. All intervals are in milliseconds.
Citation: Waldo Al, Henthorn RW, Plumb VJ, MacLean WAH: Demonstration of the mechanism transient entrainment and interruption of vertricular tachycardia with rapid atrial pacing J Am Coll Cardiol 1984,3:422-430
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Combined Application of AICD and Tachylog in Ventricular Tachyarrhythmias
An important step in the development of electrotherapy for ventricular tachyarrhythmias was the combined application of antitachycardia pacemakers and automatic cardioverter / defibrillators described in 1985 / 86 (1-3). Their use in treating life-threatening VT’s has been well documented. Almost all, modern implantable cardioverter / defibrillator (ICD) systems now combine bradycardia pacing, antitachycardia pacing, and defibrillatory options in one single device.
Figure: Diagram of the automatic implantable cardioverter / defibrillator (AICD) in combination with the antitachycardia pacemaker (Tachylog). Two screw-in leads were positioned near the anterobasal portion of the left ventricle for rate detection of the AICD. For defibrillation of the heart, two flexible patch electrodes were placed over the anterior and inferior aspects of the ventricles. The bipolar electrode of the antitachycardia pacemaker was advanced transvenously to the apex of the right ventricle.
Reference: Luderitz B, Gerckens U, Manz M (1986) Automatic implantable cardioverter / defibrillator (AICD) and antitachycardia pacemaker (Tachylog): Combined use in ventricular tachyarrhythmias, PACE 9 : 1356-1360
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The Chronotropic Assessment Exercise Protocol
The Chronotropic Assessment Exercise Protocol (CAEP) is a progressive treadmill exercise protocol designed to evaluate the appropriateness of heart rate at all levels of exertion. Pacemaker patients spend almost all of their time at exertional levels below 5 METS (metabolic equivalents) as shown in the shaded area, levels not well evaluated by traditional exercise test protocols such as the Bruce Protocol. Evaluation of chronotropic incompetence, before and after rate adaptive pacemaker implantation, permits the calculation of the Metabolic Chronotropic Relation as defined by the equation: HRstage = [(220 - age - HRrest) X (METSstage - 1) / (METSpeak - 1)] + HRrest. HRstage is the heart rate at submaximal levels of exertion that corresponds to the metabolic expenditure (METSstage) at that stage of the exercise evaluation during the CAEP protocol. Heart rate increases linearly between the resting heart rate (HRrest) and the maximal predicted heart rate (220 - age) as a percentage of the maximal exertional level that the patient can achieve METSpeak. Use of the CAEP exercise test and the Metabolic Chronotropic Relation identifies patients with chronotropic incompetence that could benefit from rate adaptive pacemakers and evaluates the adequacy of pacemaker programming after implantation.
Wilkoff BL, Corey J, Blackburn G. A Mathematical Model of the Cardiac Chronotropic Response to Exercise. Journal of Electrophysiology 1989; 3:176-180.
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His Bundle Interruption for Control of Inappropriate Ventricular Responses to Atrial Arrhythmias
e ventricle. These patients were classified as having enhanced conduction through the AV node, based on clinical and electrophysiological studies. Initially, the technique employed for His bundle interruption was, either separate or in combination, blind suture, electrocauterization, and incision of the septal portion of the right atrium. The technique later adopted was sharp division of the atrial septum at its attachment to the right fibrous trigone. Cryothermia was used in 31 patients with four failures. In the sharp division group there were two failures among 11 patients who required a second operation. Following AV node - His bundle interruption, a junctional rhythm resulted and a pacemaker was implanted.
Interruption of atrial to ventricular conduction is a satisfactory operation for disabling or life threatening atrial arrhythmias refractory to medical therapy. Cryothermic ablation is the preferable technique. If this is not successful, then division of the AV node - His bundle junction by interruption of the insertion of the atrial septum into the right fibrous trigone is required.
| Of forty-two patients with life threatening or disabling atrial arrhythmias, fifteen had Kent bundles as the basis for the reentry tachycardia, 27 had arrhythmias that originated in or above the atrioventricular (AV) node. Nineteen of the latter had an AV node that conducted atrial impulses rapidly to th |
| |
 Figure 1.
Operative procedure for sharp division of the junction of the AV node and penetrating His bundle. (A) The extent of the incision is shown by the broken line. (B) The first part of the incision allows entrance to the pyramidal space on the summit of the muscular ventricular septum. The left atrium (LA) and the AV nodal artery can be seen. This approach exposes the posterior portion of the atrial septum. (C) The separation of the atrial septum from the right fibrous trigone (RFT). The anterior extent of the atrial septum is shown with the right and left atrial walls entering. There is a chance that the epicardium in the sulcus between the two atria and the aorta will be divided. Repair is done easily. |
| Sealy WC, et al. Annals of Thoracic Surgery, 1981; 32:429-438. |
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Catheter Ablation of the A-V Junction by DC Energy in Man
Prior to 1982, ablation of the A-V junction to achieve therapeutic A-V block could only be accomplished by direct dissection of the A-V junction during open heart surgery with surgical mortality as high as 10%. Given the ability to record the His bundle by catheter technique, it seemed reasonable to consider the possibility of using catheter electrode to deliver ablative energy to the A-V junction. Our approach was to use the standard catheter electrodes in conjunction with standard D-C cardioversion apparatus. We used the unipolar mode for both recording and ablation, and the initial energy delivery was limited to 200 joules. This strategy allowed successful ablation of A-V conduction to be achieved while preserving subsidiary pacemaker function. In addition, barotraumas was minimized. No adjunctive drug therapy was required in our patients, but all obviously required permanent pacemaker implantation.
Gallagher, JJ, Svenson, RH, Kasell, JH, German, LD, Bardy, GH, Broughton, A: Catheter technique for closed chest ablation of the atrioventricular system in man: A theraputic alternative for the treatment of refractory supraventreicular tachycardia. NEJM 306:194-200, 1982
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Catheter Induced Ablation of the A-V Junction in Man
The schema depicts the equipment used for the first catheter ablation procedure performed in man. It was performed in March, 1981 at Moffitt Hospital and involved delivery of high energy D/C shocks to the region of the AV junction by means of a standard defibrillator. The patient had atrial fibrillation resistant to medical therapy and a series of D/C shocks produced complete AV block. Catheter ablation is currently used as standard technique for cure of multiple cardiac arrhythmias.
Reference: Scheinman MM,Morady F,Hess DS,Gonzalez R. Catheter-induced ablation of the atriovetricular junction to control refractory supraventricular arrhythmias. JAMA 1982; 248:851-855
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Frequency Dependent Effects of Verapamil On Atrioventricular Nodal Conduction in Man
This paper studied the mechanism of action of a commonly used antiarrhythmic drug, Verapamil, using clinical electrophysiology techniques to demonstrate a mechanism of action similar to that shown in vitro. Frequency dependent effects of antiarrhythmic drugs refers to the properties of these drugs to preferentially slow conduction during tachycardia, but have relatively little effect on conduction at normal heart rates. Studies from the basic laboratory lead to the evolution of the modulated receptor hypothesis that states that antiarrhythmic drugs attach to a binding site near the ion channel and that access of the drug to the binding site varies with the state of the channel. This study showed evidence for the presence of use-dependent blockade in humans. Evidence for its presence was inferred from the observation of frequency dependent changes in AH interval during right atrial pacing. Frequency dependent prolongation of AV nodal conduction was demonstrated in each patient, with increasing AH intervals and increasing Δ (AH) intervals. The kinetics of AH interval equilibration were rapid, similar to that observed in vitro. In conclusion, the results of this study demonstrated use-dependent blockade of AV nodal conduction with Verapamil in man, similar to what has been observed in animal models and demonstrating a mechanism for the high efficacy of Verapamil in termination of supraventricular tachycardia.
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Ellenbogen KA, German LD, O'Callaghan WG, Colavita PG, Marchese AC, Gilbert MR, Strauss HC. Frequency-dependent effects of Verapamil on atrioventricular nodal conduction in man. Circulation 1985;72:344-352.
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Head-Up Tilt Test 
The clinical investigation of syncope was advanced in 1986 by the introduction of tilt-table testing. Various types of syncope can now be clearly identified and vasovagal syncope, the most common positive result, can be classified into different collapse patterns with therapeutic implications. Tilt testing is cheap, simple and safe: it can be performed by paramedical personnel. Protocols for conduct of the test have evolved to include passive and drug challenge phases. Tilt-testing is now employed worldwide.
Kenny RA, Bayliss J, Ingram A, Sutton R. Head-up tilt test: A useful test for investigating unexplained syncope. Lancet 1986; 1:1352-4.
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The History of Steroid-Eluting Electrodes 
Mrs. Alma B., who presented with syncope and complete heart block, had a first generation Medtronic steroid-eluting lead, Model 4003 implanted on the 21st of March 1983. The custom-made pulse generator was a Medtronic Model 2443 Spectrax SXTL, which on programming 2.5 volts actually 1.6 volts. This pulse generator was designed for use with low stimulation threshold leads to improve longevity. A very small number of model 4003 leads were implanted prior to March 1983, but this case is believed to be the longest survivor with a steroid – eluting lead. Mrs. B. now 85 years, remains well and active. After thirteen years with the same pulse generator she was electively upgraded to a dual chamber system. With the output programmed to 1.6 volts (Medtronic SXTL) or 1.5 (dual chamber system), the mean auto threshold pulse width remains stable between 0.1 and 0.2 milliseconds.
Reference: Mond H, Stokes K, Helland J, et al: The Porous Titanium Steroid Eluting Electrode: A Double Blind Study Assessing the Stimulation Threshold Effects of Steroid. PACE 1988: 11;214-219
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Sudden Death and Autonomic Mechanisms 
The figure shows a plot of individual values of Baroreflex Sensitivity, grossly a marker of vagal reflexes, expressed in ms/mmHg (phenylephrine method), obtained in 192 conscious dogs one month after an anterior myocardial infarction and a few days before being exposed to a 2-min period of myocardial ischemia during a submaximal exercise test. During this "exercise and ischemia test", approximately 50% of the animals develop ventricular fibrillation (VF) and are thus defined as "susceptible" in contrast to those who survive and are defined as "resistant". Prompt defibrillation allows to test reproducibility of the events, which is above 90% for both groups.
An arbitrary gray area defines areas at different risk for the occurrence of VF: below 9 ms/mmHg the risk of VF is very high (91%) while it is relatively low (20%) above 15 ms/mmHg.
This study enlarged our own preliminary observations, already reported in 1982, and provided the first and conclusive evidence that reflex autonomic responses could be used for prognosis and, specifically, could identify the post-MI animals at high risk for VF during a new ischemic episode.
This led to the clinical evaluation of BRS as a risk stratifier and in the prospective study ATRAMI, based on 1284 post-MI patients, we confirmed our experimental findings which had paved the way for the development of the concept that an autonomic imbalance characterized by reduced vagal activity is predictive of increased risk for cardiac and arrhythmic mortality.
This work represents an example of how tight the relationship can be between experimental and clinical cardiology.
Schwartz PJ, Vanoli E, Stramba-Badiale M, De Ferrari GM, Billman GE, Foreman RD: Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 78:969 979, 1988.
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Biphasic Defibrillation Wave Form 
Perhaps the most significant improvement in implantable cadioverter defibrillator technology during the decade has involved the shift from the uniphasic to the biphasic truncated exponential waveform. Using these highly effective biphasic waveforms, less effective catheter electrode systems could be tolerated without sacrificing overall efficacy. Consequently, nearly every patient could now be adequately managed without the need for patch electrodes. This, thoracotomies for implantation became very rare-even as the weight of devices dropped to about 100 grams. A series of three basic transthoracic studies by our group, published in 1983-84, provided the firm experimental rational for the transition. Shown here is an effective waveform from on of our 1984 papers.
Schuder JC, McDaniel WC, Stoeckle H. Transthoracic defibrillation of 100kg calves with bidirection truncated exponential shocks. Trans AM Soc Artif Intern Organs 1984:30:520-524
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Use Of The Pill Electrode For Transesophageal Atrial Pacing 
Janice M, Jenkins, MacDonald Dick, Steve Collins,* William O'Neill, Robert M, Campbell, and David J, Wilber
Jenkins, J.M et al.: Use of the pill electrode for transesophageal atrial pacing. The pill electrode, which was developed for esophageal electrocardiography, has found application in transesophageal atrial pacing during procedures such as conversion of tachycardia, electrophysiologic measurement, and acceleration of heart rate to produce stress during cardiac imaging studies. Theoretical studies that examine the relationship of interelectrode distance, current level, and pulse duration to achieve successful capture agree with our clinical findings: i.e., current levels of 25 mA are effective to sustain capture; increased pulse duration reduces current requirements; and close bipolar spacing combines efficacy with safety. Results of animal studies performed to assess the extent of esophageal burn injury reveal that current levels in excess of 75 mA are required to produce lesions in short-term (under 30 minutes) pacing, and greater than 60 mA in long-term (4 hours) pacing, These results are based on experiments using a pulse duration of 2 ms, and the current levels that produce injury will be considerably lower if longer pulse durations are used, Typical current levels and pulse durations for successful capture are presented for 46 subjects in several new clinical applications, Termination of tachycardia, basic electrophysiologic measurements, and controlled acceleration of heart rate can be performed noninvasively with this technique.
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The First Rate Responsive Pacemaker Using A Hemodynamic Sensor
By: Raul Chirife MD
The hemodynamic sensor: Intracardiac impedance can be recorded using conventional pacing electrodes and requires no special hardware in the lead. Two or more electrodes can be used. Low-level, constant-current sub-threshold pulses are injected to a pair of intracardiac electrodes and the resulting voltage is detected from the same or from a different pair. The signal so obtained is the proportional to the reciprocal of the ventricular volume during the cardiac cycle, since it is modulated primarily by chamber volume (as volume decreases impedance increases). From this waveform, it is thus possible to measure amplitude changes (stroke volume) and timing parameters, such as the pre-ejection interval (PEI), known to be a marker of cardiac contractility. Such pacemakers, first implanted in humans in 1990, utilized intracardiac impedance to measure PEI and relative stroke volume changes. The device utilized right ventricular pacing leads with an additional ring electrode. The sub-threshold carrier signal was driven between the pacemaker can and the tip electrode and impedance was sensed between the two ring electrodes. Pacing rate was controlled either by PEI, a contractility marker, or by SV changes.
Chirife R. Physiological principles of a new method for rate responsive pacing using the pre-ejection interval. PACE 1988;11:1545-1554
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The Automatic Implantable Defibrillator
M. Mirowski, Morton M. Mower, and Philip R. Reid
The automatic implantable defibrillator is an electronic device programmed to monitor the cardiac rhythm continuously, to recognize ventricular fibrillation and ventricular tachyarrhythmias characterized by sinusoidal waveform, and to deliver corrective difibrillatory (author spelling) discharges when indicated. Three patients suffering from recurrent malignant ventricular arrhythmias refractory to medical therapy underwent permanent implantation of this device. Seven episodes of ventricular tachycardia and flutter-fibrillation were documented during the weeks following the implantations; two were induced at electrophysiologic studies and five occurred spontaneously. All were correctly identified and six were automatically reverted to normal sinus rhythm by the implanted device; one induced episode was cardioverted externally before the unit could recycle. Although many problems remain to be solved and the ultimate value of this therapeutic modality has to be determined, a new approached to prevention of sudden death in patients at high risk of developing lethal ventricular arrhythmias has become available.
American Heart Journal 1980;100:1089-1092
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The Cardiac Arrhythmia Suppression Trial (CAST) and the PVC Hypothesis 
Epidemiologic studies in the 70s and 80s established ventricular ectopic activity as a marker for sudden death risk following myocardial infarction. This finding led to the widespread belief that suppression of ventricular ectopics might reduce the incidence of sudden death. However, antiarrhythmic drugs available at that time produced very frequent side effects, so formal testing of this “PVC hypothesis” could not be accomplished. With the development of drugs like encainide and flecainide, that produce very few non-cardiac toxicities, CAST – which tested the PVC hypothesis – went forward. The major portion of the study was discontinued early in spring 1989 because the drugs increased mortality 2-3-fold in patients convalescing from acute myocardial infarction.
CAST is a landmark study. It changed arrhythmia practice, by focusing therapy away from asymptomatic PVCs. It changed the development of new antiarrhythmic therapies away from sodium channel block, and ensured that future therapies would be tested on “hard” endpoints like mortality. Finally, it emphasized the dangers of using ill-understood “surrogate” endpoints, like PVC suppression, as markers of important clinical effects in the absence of understanding the underlying biology. This lesson has been important not just for antiarrhythmic drugs but for all new drug development.
The CAST Investigators. Preliminary Report: Effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N Engl J Med 1989;321:406-412.
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