Arjun Sharma - Academia.edu (original) (raw)

Papers by Arjun Sharma

Research paper thumbnail of Percent right ventricular pacing predicts outcomes in the DAVID trial

Heart Rhythm, 2005

BACKGROUND The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse ... more BACKGROUND The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse outcome in patients with implantable cardioverter-defibrillators (ICDs) programmed to DDDR at 70 bpm compared with patients who had ICDs programmed to VVI backup pacing at 40 bpm. Pacing was more frequent in the DDDR group. OBJECTIVES The purpose of this study was to determine whether right ventricular pacing (RV) is an independent predictor of outcome in the DAVID trial. METHODS We evaluated the relationship of percent RV pacing to the composite endpoint of death or hospitalization for congestive heart failure. Patients who had a 3-month follow-up and who had not yet reached an endpoint were included in the study. Using Cox regression analysis (VVI group N ϭ 195; DDDR group N ϭ 185), we examined multiple factors, including percent RV pacing at 3-month follow-up, that might be associated with adverse outcomes. RESULTS Percent RV pacing as a continuous variable was correlated with the primary endpoint. As a dichotomous variable, the best separation for predicting endpoints occurred with DDDR RV pacing Ͼ40% vs DDDR RV pacing Յ40% (P ϭ .025). Patients with DDDR RV pacing Յ40% had similar or better outcomes to the VVI backup group (P ϭ .07). Correction for baseline variables predictive of the composite outcome in the (nonpaced) VVI group (use of nitrates, increased heart rate, and increased age) did not change the findings for RV pacing (P ϭ .008). In contrast, atrial pacing was not predictive of worse outcomes. CONCLUSION These results suggest, but do not prove, a causal relationship between frequent RV pacing and adverse outcomes in patients with left ventricular ejection fraction Յ40%.

Research paper thumbnail of The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study

Journal of The American College of Cardiology, 2004

We sought to evaluate approaches used to control rate, the effectiveness of rate control, and swi... more We sought to evaluate approaches used to control rate, the effectiveness of rate control, and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. BACKGROUND The AFFIRM study showed that atrial fibrillation (AF) can be treated effectively with rate control and anticoagulation, but drug efficacy to control rate remains uncertain.

Research paper thumbnail of Vagal techniques for termination of paroxysmal supraventricular tachycardia

American Journal of Cardiology, 1980

Maneuvers that reflexly increase vagal tone were deployed to terminate the tachycardia in 68 cons... more Maneuvers that reflexly increase vagal tone were deployed to terminate the tachycardia in 68 consecutive patients with paroxysmal supraventricular tachycardia. The order and success rate of the protocol was as follows: 57 episodes were terminated with carotid sinus pressure alone or after pretreatment with edrophonium, 5 were terminated with the Valsalva maneuvers and 6 were terminated with phenylephrine. Potency testing showed that phenylephrine evoked the greatest increase in vagal tone. All cases demonstrated slowing of tachycardia ranging from 40 to 220 ms +/- standard error of the mean (mean 79.0 +/- 3.8 ms) followed by abrupt termination. Pauses after termination ranged from 900 to 3,300 ms (mean 1,683.8 +/- 66.6) with 54 patients showing pauses of 2,000 ms or less. Termination was highly reproducible showing an overall success of 148 (92 percent) of 160 trials among 22 selected cases. The extent of increased vagal tone needed to terminate paroxysmal supraventricular tachycardia was raised by augmented sympathetic tone (infusion of isoproterenol) and decreased by reduced sympathetic tone (pretreatment with propranolol). Thus, paroxysmal supraventricular tachycardia can be rapidly, safety and consistently terminated by maneuvers that reflexly increase vagal tone.

Research paper thumbnail of Reflex mechanisms responsible for early spontaneous termination of paroxysmal supraventricular tachycardia

American Journal of Cardiology, 1982

The American Journal of CARDIOLOGY°V OLUME 49 NUMBER 2

Research paper thumbnail of Electrophysiologic effects, clinical efficacy and safety of intravenous and oral nadolol in refractory supraventricular tachyarrhythmias

American Journal of Cardiology, 1987

The electrocardiographic and electrophysiologic effects, cllnical efficacy and safety of intraven... more The electrocardiographic and electrophysiologic effects, cllnical efficacy and safety of intravenous and oral nadolol therapy were examined in 34 patients with recurrent supraventricular tachyarrhythmias (SW) undergoing electrophysiologic evaluation. Programmed electrical stimulation was performed in the control (drug-free) state, after infusion of intravenous nadolol (mean dose 0.09 f 0.03 mg/kg) and after chronic oral nadolol therapy in patients who responded to intravenous nadolol (mean dose 83 f 12 mg for 5 days). Intravenous nadolol administration prolonged mean sinus cycle length (p = O.OOS), mean PR interval (p = 0.001) and mean AH Interval (p = O.OOl), with no slgnlficant electrophysiologic effects In the atrium, ventricle or accessory bypass tracts. Oral nadolol had similar electrocardiographic and electrophysiologlc effects, but of lesser magnitude. Intravenous nadolol resulted in complete suppression of induced SVT In 78% of patients with sinus and atrloventricular nodal reentrant tachycardla and 11% of patients with atrioventricular (AV) reentrant tachycardia (p <O.OOl). Partial responses were frequent in intraatrial or AV reentrant tachycardia (37 % ). Oral nadolol suppressed induction of SVT in patients who responded to intravenous nadolol. Adverse reactions to intravenous and oral nadolol were infrequent-8% and 8%) respectively-and usually dii not require drug wlthdrawal. Intravenous nadolol is hiihly effective in sinus and AV nodal reentrant tachycardia, and a successful electrophysiologic response to it predicts efficacy of long-term oral nadolol therapy. It has limited efficacy alone in AV reentrant tachycardia and should be considered in combination with other antiarrhythmic therapy in this type of SW.

Research paper thumbnail of Right ventricular pressure during ventricular arrhythmias in humans: potential implications for implantable antitachycardia devices

Journal of The American College of Cardiology, 1990

Research paper thumbnail of Relation Between clinical presentation and induced arrhythmias in the Wolff-Parkinson-White syndrome

American Journal of Cardiology, 1987

Electrophysiologic testing is warranted in patients with the Wolff-Parkinson-White (WPW) syndrome... more Electrophysiologic testing is warranted in patients with the Wolff-Parkinson-White (WPW) syndrome presenting with rapid atrial fibrillation (AF) or ventricular fibrillation. Indications are less clear in patients presenting only with atrioventricular reentrant tachycardia (ART). A knowledge of propensity of this latter group to show a rapid ventricular response in the event of AF and the ability of electrophysiologic testing to reproduce the type and rate of clinical arrhythmias are relevant to this decision. The records of 126 symptomatic patients with manifest WPW syndrome were reviewed and separated into 4 groups according to presentation: group l-AF; group P-ART; group 3-palpitations suggesting ART; and group 4-AF and ART. All patients except those in group 3 had electrocardiographically documented clinical arrhythmias, and these arrhythmias were compared with those induced during electrophysiologic testing. The shortest RR interval during induced AF and the cycle length of induced ART correlated well with those occurring clinically (r = 0.72, p <O.OOOOl), as did the cycle length of induced ART (r = 0.79, p <O.OOOOl). Patients presenting with AF (65% ) had a higher incidence of atrial vulnerability (46%) and sustained AF at electrophysiologic testing than those presenting with ART (16 % and 5 % ) or undocumented palpitations (27 % and 21% ). Forty-one percent of patients with ART and 51% with undocumented palpitations had potentially lethal rates (shortest RR interval <250 ms) during induced AF. The ability to reproduce clinical arrhythmias and the frequency of rapid rates during AF induced in patients presenting with only ART or undocumented palpitations supports the recommendation for electrophysiologic testing in symptomatic patients with WPW. (Am J Cardiol 1967;60:576-579) T here is general agreement that therapy guided by electrophysiologic testing is indicated in patients with Wolff-Parkinson-White (WPW] syndrome who present with atria1 fibrillation (AF] and a rapid ventricular response over the accessory pathway.1 It is less clear whether electrophysiologic testing is necessary in patients with anterograde preexcitation presenting with well tolerated atrioventricular reentrant tachycardia (ART] or undocumented palpitations suggestive of ART. Knowledge of the propensity of the latter groups to have a rapid ventricular response to AF may be helpful in addressing this issue. We compared the electrophysiologic properties of the accessory pathway in patients presenting with ART or with undocument-

Research paper thumbnail of Closed-Heart Technique for Wolff-Parkinson-White Syndrome: Further Experience and Potential Limitations

Annals of Thoracic Surgery, 1986

We have described a closed-heart technique for division of atrioventricular (AV) pathways in Wolf... more We have described a closed-heart technique for division of atrioventricular (AV) pathways in Wolff-Parkinson-White (WPW) syndrome. The technique involves dissection and mobilization of the AV fat pad with exposure and cryoablation of the AV junction at the site of the AV pathways.

Research paper thumbnail of Nodoventricular” accessory pathway: Evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties

Journal of The American College of Cardiology, 1988

Research paper thumbnail of An Algorithm for the Electrocardiographic Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome

Pace-pacing and Clinical Electrophysiology, 1987

Accessory pathway location in the Wolff-Parkinson-White syndrome influences the success and morbi... more Accessory pathway location in the Wolff-Parkinson-White syndrome influences the success and morbidity of nonpharmacological therapies, so that an estimate of accessory pathway location is relevant to the practicing physician. We derived an algorithm for accessory pathway localization based on the surface electrocardiogram; we tested it in a population of 141 patients with the Wolff-Parkinson-White syndrome in whom accessory pathway localization was made by electrophysiological and/or intraoperative mapping. The goal of the algorithm was to localize the accessory pathway to one of four anatomic regions, namely, left free wall, posteroseptal, anteroseptal or right free wall by using a simple, easy-to-appiy scheme. Each of two observers, blinded to the results of mapping, correctly identified the anatomic location of 91% and 90% of pathways, respectively. We conclude that a simple algorithm utilizing the 12-lead electrocardiogram can provide a valuable first approximation of accessory pathway location in the Wolff-Parkinson-White syndrome.

Research paper thumbnail of Improving SVT Discrimination in Single-Chamber ICDs: A New Electrogram Morphology-Based Algorithm

Journal of Cardiovascular Electrophysiology, 2006

Introduction: Wide-spread adoption of ICD therapy has focused efforts on improving the quality of... more Introduction: Wide-spread adoption of ICD therapy has focused efforts on improving the quality of life for patients by reducing “inappropriate” shock therapies. To this end, distinguishing supraventricular tachycardia from ventricular tachycardia remains a major challenge for ICDs. More sophisticated discrimination algorithms based on ventricular electrogram morphology have been made practicable by the increased computational ability of modern ICDs.Methods and Results: We report results from a large prospective study (1,122 pts) of a new ventricular electrogram morphology tachycardia discrimination algorithm (Wavelet™ Dynamic Discrimination, Medtronic, Minneapolis, MN, USA) operating at minimal algorithm setting (RV coil-can electrogram, match threshold of 70%). This is a nonrandomized cohort study of ICD patients using the morphology discrimination of the Wavelet algorithm to distinguish SVT and VT/VF. The Wavelet criterion was required ON in all patients and all other supraventricular tachycardia discriminators were required to be OFF. Spontaneous episodes (N = 2,235) eligible for ICD therapy were adjudicated for detection algorithm performance. The generalized estimating equations method was used to remove bias introduced when an individual patient contributes multiple episodes. Inappropriate therapies for supraventricular tachycardia were reduced by 78% (90% CI: 72.8–82.9%) for episodes within the range of rates where Wavelet was programmed to discriminate. Sensitivity for sustained ventricular tachycardia was 98.6% (90% CI: 97–99.3%) without the use of high-rate time out.Conclusions: Results from this prospective study of the Wavelet electrogram morphology discrimination algorithm operating as the sole discriminator in the ON mode demonstrate that inappropriate therapy for supraventricular tachycardia in a single-chamber ICD can be dramatically reduced compared to rate detection alone.

Research paper thumbnail of Cryosurgical modification of the atrioventricular node: A closed heart approach in the dog

Journal of The American College of Cardiology, 1987

Intraoperative modification of the atrioventricular (AV) node to prolong refractoriness could be ... more Intraoperative modification of the atrioventricular (AV) node to prolong refractoriness could be an alternative to His bundle ablation in patients with refractory supraventricular arrhythmias. It was postulated that a cryosurgical lesion at the posterior interatrial septum in the closed heart could achieve this. An electrophysiologic study was performed in anesthetized dogs. The AV fat pad was mobilized to expose the posteroseptal region. A cryoprobe cooled to 0 to -lOoe was moved in the exposed region until reversible AV block indicated proximity of the AV node. The probe was then cooled to -70 0 e for 30 seconds.

Research paper thumbnail of Defibrillation Threshold: A Simple and Quantitative Estimate of the Ability to Defibrillate

Pace-pacing and Clinical Electrophysiology, 1987

It has recently been shown that the probability of successful defibrillation as a function of ene... more It has recently been shown that the probability of successful defibrillation as a function of energy has a sigmoidal dose-response relationship. Determination of a defibrillation “dose-response curve” is time consuming and requires multiple defibrillation attempts. On the other hand, determination of a defibrillation threshold is achieved rapidly and would be better suited to study the effect of interventions on the ability to defibrillate patients. We assessed the relationship of defibrillation threshold to the defibrillation “dose-response curve” in twelve open chest, halotbane anesthetized pigs. Ventricular fibrillation was induced electrically, and defibrillation was attempted by passing sequentiai puise shocks through an indwelling catheter and plaque electrodes. Defibrillation threshold was determined by decreasing the stored voltage of the initial shock until it failed to defibrillate the heart. Five different stored voltage levels distributed around defibrillation threshold were then randomly administered, six times for each level. A “dose-response curve” was obtained for each animal. Defibrillation threshold superimposed on the “dose-response curve” at 76 ± 7.2 percent (mean ± SEM) defibrillation success. Energy delivered at 1.5 times average defibrillation threshold was predicted to achieve 100 percent defibrillation success for a single shock in all animals. We conclude that defibrillation threshold provides a simple and quantitative estimate of the ability to defibrillate with a predictable relationship to the “dose-response curve.”

Research paper thumbnail of Longitudinal Electrophysiologic Assessment of Asymptomatic Patients with the Wolff–Parkinson–White Electrocardiographs Pattern

New England Journal of Medicine, 1989

Although most asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern h... more Although most asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern have a good prognosis, some die suddenly. The mechanism of sudden death is usually ventricular fibrillation, which is triggered by atrial fibrillation with a rapid ventricular response rate. Electrophysiologic testing has been proposed to identify asymptomatic patients who may be at risk for sudden death. Meaningful application of such testing requires a knowledge of whether the electrophysiologic measurements are reproducible over time. Consequently, we performed electrophysiologic studies on two occasions at least 36 months apart (mean +/- SD, 54.7 +/- 14) in 29 asymptomatic patients with the pattern. Twenty-seven patients remained asymptomatic, and sustained supraventricular tachycardia developed in two during the follow-up period. Nine patients (31 percent) lost the capacity for preexcitation and anterograde conduction over the accessory pathway, which produces the Wolff-Parkinson-White pattern. The others had little change in measurements of conduction over the accessory pathway. Patients who lost conduction over the accessory pathway tended to be older (mean +/- SD, 50 +/- 18 vs. 39 +/- 11 years; P = 0.06) than patients who retained preexcitation, and they had longer anterograde effective refractory periods at the first assessment (414 +/- 158 vs. 295 +/- 27 msec; P = 0.003). We conclude that a considerable number of asymptomatic patients with the Wolff-Parkinson-White pattern lose their capacity for anterograde conduction over the accessory pathway. This loss of capacity probably contributes to the low mortality among asymptomatic patients.

Research paper thumbnail of Diagnostic Assessment of Recurrent Syncope

Pace-pacing and Clinical Electrophysiology, 1984

The definitive diagnosis of a cardiac arrhythmia as the basis for syncope is made by electrocardi... more The definitive diagnosis of a cardiac arrhythmia as the basis for syncope is made by electrocardiographic monitoring during a syncopal episode. In the absence of this evidence, abnormalities demonstrated by an electrophysiologic study may suggest the etiology of syncope. Cardiac electrophysiologic testing in patients with recurrent syncope should probably be limited to patients with underlying cardiac disease. These patients are at a higher risk for sudden death and have a high incidence of electrophysiologic abnormalities. In particular, ventricular tachycardia may be evoked and specific therapy for this abnormality is associated with remission of syncope. In contrast, electrophysiologic studies in patients with no underlying cardiac disease have a very low yield of abnormal findings in the order of 10–20%, and should be performed only when there are reasons to suspect the presence of arrhythmias. Furthermore, in patients with no underlying cardiovascular disease there is a high spontaneous remission rate of syncope and the late incidence of sudden death is low, and related to the presence of other systemic illnesses. At present, the significance of nonsustained ventricular tachycardia or ventricular fibrillation induced during cardiac electrophysiologic studies in patients with no documented arrhythmias is unknown, and further prospective studies are necessary to define appropriate therapy for these patients. Further investigation is also required to clarify the spontaneous remission rate of syncope, as this information is of vital importance in assessing the success of any therapeutic modality.

Research paper thumbnail of Controlled Cryothermal Injury to the AV Node: Feasibility for AV Nodal Modification

Pace-pacing and Clinical Electrophysiology, 1985

Elective subtotal injury to the AV node-His bundle region may create a negative dromotropic effec... more Elective subtotal injury to the AV node-His bundle region may create a negative dromotropic effect to provide a therapeutic advantage in some patients with supraventricular tachycardia without creating complete AV block. We examined the effects of cryosurgery to the AV nodal region, varying temperature and time using a 15 mm circular cryoprobe applied directly to the canine AV node-His bundle region. Twelve dogs were anesthetized and the heart was exposed through a right thoracotomy. Electrophysiological data obtained included conduction intervals, incremental pacing, and extrastimulus testing. Under inflow occlusion, the cryoprobe was positioned over the AV node-His bundle region using anatomical landmarks and a single freeze was applied (–15°C to –60°C, 15 to 60 seconds). Dogs were allowed to recover for 1 month, after which time electrophysiological testing was repeated under similar conditions; then the animals were sacrificed. With probe temperatures of –60°C for 15 to 60 seconds, five of six dogs experienced complete heart block with dense fibrosis observed in the AV nodal-His bundle region. After freezing with higher temperatures, the remaining seven dogs had return of atrioventricular conduction postoperatively with prolongation of AH time observed in five and marked prolongation of the Wenckebach cycle length in three of the five. We conclude that controlled cryothermal injury to the AV node-His bundle region may be useful to create a desirable negative dromotropic response without creating complete AV block.

Research paper thumbnail of Effects of lidocaine and verapamil on defibrillation in humans

Journal of Electrocardiology, 1991

Patients with automatic dehbrillators frequently require chronic antiarrhythmic drug therapy or r... more Patients with automatic dehbrillators frequently require chronic antiarrhythmic drug therapy or receive acute therapy with the onset of symptoms. The effects on energy requirements for defibrillation of lidocaine hydrochloride and verapamil hydrochloride, two commonly used antiarrhythmic agents, were examined in 20 successive patients undergoing corrective arrhythmia surgery. The minimum energy requirement for ventricular defibrillation before and 5 minutes after the administration of 150 mg of lidocaine intravenously (n = 8), or 10 minutes after 10 mg of verapamil intravenously (n = 12), were determined. Each patient was assigned to receive either verapamil or Iidocaine. Three mesh coil defibrillating electrodes (Medtronic 6891, 6892) were sutured to the epicardium of the right and left ventricles. Ventricular fibrillation was induced using alternating current. After a minimum of 10 seconds of fibrillation, the minimum energy for defibrillation was established using sequential pulse defibrillation. The preselected drug was then infused and the ventricular defibrillation energy was again determined after 5 or 10 minutes circulation time. Lidocaine did not alter the minimum energy for defibrillation (3.0 _' I.4 J vs. 3.0 k 1.8 J, mean k SD), despite plasma levels of lidocaine that averaged 13.2 t I.9 pmol/l. In contrast, verapamil significantly increased (3.9 k 2.2 J vs. 6.5 2 2.9 J) the minimum energy necessary for defibrillation. The difference in defibrillation energy was significantly correlated to the fall in systolic blood pressure induced by verapamil administration (r = 0.72). These data reinforce the necessity for determining efficacy of defibrillation when medication changes are instituted. Verapamil should be used with caution in patients with automatic deiibrillators and marginal defibrillation threshold.

Research paper thumbnail of Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: Importance of atrial fibrillatory cycle length

Journal of The American College of Cardiology, 1990

The effects of intravenous procainamide (n = 30) or prepotentate (n = 25) were evaluated in 55 pa... more The effects of intravenous procainamide (n = 30) or prepotentate (n = 25) were evaluated in 55 patients with acute .trial fibrillation and the Wolff-Pi rkinson-White syndrome. All patients received either procainamide (12 to 15 mg)kg body weight) or propafenone (I to 2 mglkg) during sustained (>10 min) atria) fibrillation or after termination of nonsustatned atria) fibrillation. Termination of atrtut fibrillation was attributed to a drug if it occurred -15 min after infusion . Measurements included mean cycle length of fibritlatory electrograms (mean AA interval) as measured at the high right atrium and shortest RR Interval between pre-excited cycles during atriai fibrillation.

Research paper thumbnail of Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome

Pace-pacing and Clinical Electrophysiology, 1989

SZABO, T.S., et al.: Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome Ope... more SZABO, T.S., et al.: Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome Operative and ablative therapy in the Wolff-Parkinson-White syndrome requires accurate localization of accessory atrioventricular pathways. A reasonable first approximation to pathway location can be obtained by noninvasive techniques, the 12-lead electrocardiogram being the most readily available of these. Accurate characterization of the number and anatomic localization of accessory pathways still requires invasive electrophysiological assessment. The most useful technique for accessory pathway localization remains endocardial atrial mapping of the tricuspid and mitral (via the coronary sinus) ring during atrioventricular reciprocating tachycardia and ventricular pacing. Other techniques provide important confirmatory evidence and may be the only guides to accessory pathway location in selected individuals.

Research paper thumbnail of Results of operative therapy in the permanent form of junctional reciprocating tachycardia

American Journal of Cardiology, 1989

To assess the results of operative therapy for permanent junctional reciprocating tachycardia, a ... more To assess the results of operative therapy for permanent junctional reciprocating tachycardia, a type of incessant tachycardia, the ctintcal and electrophysiologic data of 8 such patients referred for management of tachycardia were reviewed. The duration of incessant tachycardia was 14 f 10 years (range 2 to 30). The heart rate at rest during tachycardia ranged from 120 to 150 beats/min. Pour of S patients had cardiomegaly or depressed ejection fraction (16 f lo%, range 5 to 27) at pre sentation and, of these, 2 had symptoms of congestive heart failure. Exertional dyspnea despite normal left ventricular function Was noted in 1 patient, 2 had chronic palpitations and 3 were asymptomatic. Electrophysiologic data confirmed the presence of a posteroseptal pathway with atrioventricular node-like properties conducting slowly in the retrograde direction only.

Research paper thumbnail of Percent right ventricular pacing predicts outcomes in the DAVID trial

Heart Rhythm, 2005

BACKGROUND The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse ... more BACKGROUND The Dual-Chamber and VVI Implantable Defibrillator (DAVID) trial demonstrated a worse outcome in patients with implantable cardioverter-defibrillators (ICDs) programmed to DDDR at 70 bpm compared with patients who had ICDs programmed to VVI backup pacing at 40 bpm. Pacing was more frequent in the DDDR group. OBJECTIVES The purpose of this study was to determine whether right ventricular pacing (RV) is an independent predictor of outcome in the DAVID trial. METHODS We evaluated the relationship of percent RV pacing to the composite endpoint of death or hospitalization for congestive heart failure. Patients who had a 3-month follow-up and who had not yet reached an endpoint were included in the study. Using Cox regression analysis (VVI group N ϭ 195; DDDR group N ϭ 185), we examined multiple factors, including percent RV pacing at 3-month follow-up, that might be associated with adverse outcomes. RESULTS Percent RV pacing as a continuous variable was correlated with the primary endpoint. As a dichotomous variable, the best separation for predicting endpoints occurred with DDDR RV pacing Ͼ40% vs DDDR RV pacing Յ40% (P ϭ .025). Patients with DDDR RV pacing Յ40% had similar or better outcomes to the VVI backup group (P ϭ .07). Correction for baseline variables predictive of the composite outcome in the (nonpaced) VVI group (use of nitrates, increased heart rate, and increased age) did not change the findings for RV pacing (P ϭ .008). In contrast, atrial pacing was not predictive of worse outcomes. CONCLUSION These results suggest, but do not prove, a causal relationship between frequent RV pacing and adverse outcomes in patients with left ventricular ejection fraction Յ40%.

Research paper thumbnail of The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study

Journal of The American College of Cardiology, 2004

We sought to evaluate approaches used to control rate, the effectiveness of rate control, and swi... more We sought to evaluate approaches used to control rate, the effectiveness of rate control, and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. BACKGROUND The AFFIRM study showed that atrial fibrillation (AF) can be treated effectively with rate control and anticoagulation, but drug efficacy to control rate remains uncertain.

Research paper thumbnail of Vagal techniques for termination of paroxysmal supraventricular tachycardia

American Journal of Cardiology, 1980

Maneuvers that reflexly increase vagal tone were deployed to terminate the tachycardia in 68 cons... more Maneuvers that reflexly increase vagal tone were deployed to terminate the tachycardia in 68 consecutive patients with paroxysmal supraventricular tachycardia. The order and success rate of the protocol was as follows: 57 episodes were terminated with carotid sinus pressure alone or after pretreatment with edrophonium, 5 were terminated with the Valsalva maneuvers and 6 were terminated with phenylephrine. Potency testing showed that phenylephrine evoked the greatest increase in vagal tone. All cases demonstrated slowing of tachycardia ranging from 40 to 220 ms +/- standard error of the mean (mean 79.0 +/- 3.8 ms) followed by abrupt termination. Pauses after termination ranged from 900 to 3,300 ms (mean 1,683.8 +/- 66.6) with 54 patients showing pauses of 2,000 ms or less. Termination was highly reproducible showing an overall success of 148 (92 percent) of 160 trials among 22 selected cases. The extent of increased vagal tone needed to terminate paroxysmal supraventricular tachycardia was raised by augmented sympathetic tone (infusion of isoproterenol) and decreased by reduced sympathetic tone (pretreatment with propranolol). Thus, paroxysmal supraventricular tachycardia can be rapidly, safety and consistently terminated by maneuvers that reflexly increase vagal tone.

Research paper thumbnail of Reflex mechanisms responsible for early spontaneous termination of paroxysmal supraventricular tachycardia

American Journal of Cardiology, 1982

The American Journal of CARDIOLOGY°V OLUME 49 NUMBER 2

Research paper thumbnail of Electrophysiologic effects, clinical efficacy and safety of intravenous and oral nadolol in refractory supraventricular tachyarrhythmias

American Journal of Cardiology, 1987

The electrocardiographic and electrophysiologic effects, cllnical efficacy and safety of intraven... more The electrocardiographic and electrophysiologic effects, cllnical efficacy and safety of intravenous and oral nadolol therapy were examined in 34 patients with recurrent supraventricular tachyarrhythmias (SW) undergoing electrophysiologic evaluation. Programmed electrical stimulation was performed in the control (drug-free) state, after infusion of intravenous nadolol (mean dose 0.09 f 0.03 mg/kg) and after chronic oral nadolol therapy in patients who responded to intravenous nadolol (mean dose 83 f 12 mg for 5 days). Intravenous nadolol administration prolonged mean sinus cycle length (p = O.OOS), mean PR interval (p = 0.001) and mean AH Interval (p = O.OOl), with no slgnlficant electrophysiologic effects In the atrium, ventricle or accessory bypass tracts. Oral nadolol had similar electrocardiographic and electrophysiologlc effects, but of lesser magnitude. Intravenous nadolol resulted in complete suppression of induced SVT In 78% of patients with sinus and atrloventricular nodal reentrant tachycardla and 11% of patients with atrioventricular (AV) reentrant tachycardia (p <O.OOl). Partial responses were frequent in intraatrial or AV reentrant tachycardia (37 % ). Oral nadolol suppressed induction of SVT in patients who responded to intravenous nadolol. Adverse reactions to intravenous and oral nadolol were infrequent-8% and 8%) respectively-and usually dii not require drug wlthdrawal. Intravenous nadolol is hiihly effective in sinus and AV nodal reentrant tachycardia, and a successful electrophysiologic response to it predicts efficacy of long-term oral nadolol therapy. It has limited efficacy alone in AV reentrant tachycardia and should be considered in combination with other antiarrhythmic therapy in this type of SW.

Research paper thumbnail of Right ventricular pressure during ventricular arrhythmias in humans: potential implications for implantable antitachycardia devices

Journal of The American College of Cardiology, 1990

Research paper thumbnail of Relation Between clinical presentation and induced arrhythmias in the Wolff-Parkinson-White syndrome

American Journal of Cardiology, 1987

Electrophysiologic testing is warranted in patients with the Wolff-Parkinson-White (WPW) syndrome... more Electrophysiologic testing is warranted in patients with the Wolff-Parkinson-White (WPW) syndrome presenting with rapid atrial fibrillation (AF) or ventricular fibrillation. Indications are less clear in patients presenting only with atrioventricular reentrant tachycardia (ART). A knowledge of propensity of this latter group to show a rapid ventricular response in the event of AF and the ability of electrophysiologic testing to reproduce the type and rate of clinical arrhythmias are relevant to this decision. The records of 126 symptomatic patients with manifest WPW syndrome were reviewed and separated into 4 groups according to presentation: group l-AF; group P-ART; group 3-palpitations suggesting ART; and group 4-AF and ART. All patients except those in group 3 had electrocardiographically documented clinical arrhythmias, and these arrhythmias were compared with those induced during electrophysiologic testing. The shortest RR interval during induced AF and the cycle length of induced ART correlated well with those occurring clinically (r = 0.72, p <O.OOOOl), as did the cycle length of induced ART (r = 0.79, p <O.OOOOl). Patients presenting with AF (65% ) had a higher incidence of atrial vulnerability (46%) and sustained AF at electrophysiologic testing than those presenting with ART (16 % and 5 % ) or undocumented palpitations (27 % and 21% ). Forty-one percent of patients with ART and 51% with undocumented palpitations had potentially lethal rates (shortest RR interval <250 ms) during induced AF. The ability to reproduce clinical arrhythmias and the frequency of rapid rates during AF induced in patients presenting with only ART or undocumented palpitations supports the recommendation for electrophysiologic testing in symptomatic patients with WPW. (Am J Cardiol 1967;60:576-579) T here is general agreement that therapy guided by electrophysiologic testing is indicated in patients with Wolff-Parkinson-White (WPW] syndrome who present with atria1 fibrillation (AF] and a rapid ventricular response over the accessory pathway.1 It is less clear whether electrophysiologic testing is necessary in patients with anterograde preexcitation presenting with well tolerated atrioventricular reentrant tachycardia (ART] or undocumented palpitations suggestive of ART. Knowledge of the propensity of the latter groups to have a rapid ventricular response to AF may be helpful in addressing this issue. We compared the electrophysiologic properties of the accessory pathway in patients presenting with ART or with undocument-

Research paper thumbnail of Closed-Heart Technique for Wolff-Parkinson-White Syndrome: Further Experience and Potential Limitations

Annals of Thoracic Surgery, 1986

We have described a closed-heart technique for division of atrioventricular (AV) pathways in Wolf... more We have described a closed-heart technique for division of atrioventricular (AV) pathways in Wolff-Parkinson-White (WPW) syndrome. The technique involves dissection and mobilization of the AV fat pad with exposure and cryoablation of the AV junction at the site of the AV pathways.

Research paper thumbnail of Nodoventricular” accessory pathway: Evidence for a distinct accessory atrioventricular pathway with atrioventricular node-like properties

Journal of The American College of Cardiology, 1988

Research paper thumbnail of An Algorithm for the Electrocardiographic Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome

Pace-pacing and Clinical Electrophysiology, 1987

Accessory pathway location in the Wolff-Parkinson-White syndrome influences the success and morbi... more Accessory pathway location in the Wolff-Parkinson-White syndrome influences the success and morbidity of nonpharmacological therapies, so that an estimate of accessory pathway location is relevant to the practicing physician. We derived an algorithm for accessory pathway localization based on the surface electrocardiogram; we tested it in a population of 141 patients with the Wolff-Parkinson-White syndrome in whom accessory pathway localization was made by electrophysiological and/or intraoperative mapping. The goal of the algorithm was to localize the accessory pathway to one of four anatomic regions, namely, left free wall, posteroseptal, anteroseptal or right free wall by using a simple, easy-to-appiy scheme. Each of two observers, blinded to the results of mapping, correctly identified the anatomic location of 91% and 90% of pathways, respectively. We conclude that a simple algorithm utilizing the 12-lead electrocardiogram can provide a valuable first approximation of accessory pathway location in the Wolff-Parkinson-White syndrome.

Research paper thumbnail of Improving SVT Discrimination in Single-Chamber ICDs: A New Electrogram Morphology-Based Algorithm

Journal of Cardiovascular Electrophysiology, 2006

Introduction: Wide-spread adoption of ICD therapy has focused efforts on improving the quality of... more Introduction: Wide-spread adoption of ICD therapy has focused efforts on improving the quality of life for patients by reducing “inappropriate” shock therapies. To this end, distinguishing supraventricular tachycardia from ventricular tachycardia remains a major challenge for ICDs. More sophisticated discrimination algorithms based on ventricular electrogram morphology have been made practicable by the increased computational ability of modern ICDs.Methods and Results: We report results from a large prospective study (1,122 pts) of a new ventricular electrogram morphology tachycardia discrimination algorithm (Wavelet™ Dynamic Discrimination, Medtronic, Minneapolis, MN, USA) operating at minimal algorithm setting (RV coil-can electrogram, match threshold of 70%). This is a nonrandomized cohort study of ICD patients using the morphology discrimination of the Wavelet algorithm to distinguish SVT and VT/VF. The Wavelet criterion was required ON in all patients and all other supraventricular tachycardia discriminators were required to be OFF. Spontaneous episodes (N = 2,235) eligible for ICD therapy were adjudicated for detection algorithm performance. The generalized estimating equations method was used to remove bias introduced when an individual patient contributes multiple episodes. Inappropriate therapies for supraventricular tachycardia were reduced by 78% (90% CI: 72.8–82.9%) for episodes within the range of rates where Wavelet was programmed to discriminate. Sensitivity for sustained ventricular tachycardia was 98.6% (90% CI: 97–99.3%) without the use of high-rate time out.Conclusions: Results from this prospective study of the Wavelet electrogram morphology discrimination algorithm operating as the sole discriminator in the ON mode demonstrate that inappropriate therapy for supraventricular tachycardia in a single-chamber ICD can be dramatically reduced compared to rate detection alone.

Research paper thumbnail of Cryosurgical modification of the atrioventricular node: A closed heart approach in the dog

Journal of The American College of Cardiology, 1987

Intraoperative modification of the atrioventricular (AV) node to prolong refractoriness could be ... more Intraoperative modification of the atrioventricular (AV) node to prolong refractoriness could be an alternative to His bundle ablation in patients with refractory supraventricular arrhythmias. It was postulated that a cryosurgical lesion at the posterior interatrial septum in the closed heart could achieve this. An electrophysiologic study was performed in anesthetized dogs. The AV fat pad was mobilized to expose the posteroseptal region. A cryoprobe cooled to 0 to -lOoe was moved in the exposed region until reversible AV block indicated proximity of the AV node. The probe was then cooled to -70 0 e for 30 seconds.

Research paper thumbnail of Defibrillation Threshold: A Simple and Quantitative Estimate of the Ability to Defibrillate

Pace-pacing and Clinical Electrophysiology, 1987

It has recently been shown that the probability of successful defibrillation as a function of ene... more It has recently been shown that the probability of successful defibrillation as a function of energy has a sigmoidal dose-response relationship. Determination of a defibrillation “dose-response curve” is time consuming and requires multiple defibrillation attempts. On the other hand, determination of a defibrillation threshold is achieved rapidly and would be better suited to study the effect of interventions on the ability to defibrillate patients. We assessed the relationship of defibrillation threshold to the defibrillation “dose-response curve” in twelve open chest, halotbane anesthetized pigs. Ventricular fibrillation was induced electrically, and defibrillation was attempted by passing sequentiai puise shocks through an indwelling catheter and plaque electrodes. Defibrillation threshold was determined by decreasing the stored voltage of the initial shock until it failed to defibrillate the heart. Five different stored voltage levels distributed around defibrillation threshold were then randomly administered, six times for each level. A “dose-response curve” was obtained for each animal. Defibrillation threshold superimposed on the “dose-response curve” at 76 ± 7.2 percent (mean ± SEM) defibrillation success. Energy delivered at 1.5 times average defibrillation threshold was predicted to achieve 100 percent defibrillation success for a single shock in all animals. We conclude that defibrillation threshold provides a simple and quantitative estimate of the ability to defibrillate with a predictable relationship to the “dose-response curve.”

Research paper thumbnail of Longitudinal Electrophysiologic Assessment of Asymptomatic Patients with the Wolff–Parkinson–White Electrocardiographs Pattern

New England Journal of Medicine, 1989

Although most asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern h... more Although most asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern have a good prognosis, some die suddenly. The mechanism of sudden death is usually ventricular fibrillation, which is triggered by atrial fibrillation with a rapid ventricular response rate. Electrophysiologic testing has been proposed to identify asymptomatic patients who may be at risk for sudden death. Meaningful application of such testing requires a knowledge of whether the electrophysiologic measurements are reproducible over time. Consequently, we performed electrophysiologic studies on two occasions at least 36 months apart (mean +/- SD, 54.7 +/- 14) in 29 asymptomatic patients with the pattern. Twenty-seven patients remained asymptomatic, and sustained supraventricular tachycardia developed in two during the follow-up period. Nine patients (31 percent) lost the capacity for preexcitation and anterograde conduction over the accessory pathway, which produces the Wolff-Parkinson-White pattern. The others had little change in measurements of conduction over the accessory pathway. Patients who lost conduction over the accessory pathway tended to be older (mean +/- SD, 50 +/- 18 vs. 39 +/- 11 years; P = 0.06) than patients who retained preexcitation, and they had longer anterograde effective refractory periods at the first assessment (414 +/- 158 vs. 295 +/- 27 msec; P = 0.003). We conclude that a considerable number of asymptomatic patients with the Wolff-Parkinson-White pattern lose their capacity for anterograde conduction over the accessory pathway. This loss of capacity probably contributes to the low mortality among asymptomatic patients.

Research paper thumbnail of Diagnostic Assessment of Recurrent Syncope

Pace-pacing and Clinical Electrophysiology, 1984

The definitive diagnosis of a cardiac arrhythmia as the basis for syncope is made by electrocardi... more The definitive diagnosis of a cardiac arrhythmia as the basis for syncope is made by electrocardiographic monitoring during a syncopal episode. In the absence of this evidence, abnormalities demonstrated by an electrophysiologic study may suggest the etiology of syncope. Cardiac electrophysiologic testing in patients with recurrent syncope should probably be limited to patients with underlying cardiac disease. These patients are at a higher risk for sudden death and have a high incidence of electrophysiologic abnormalities. In particular, ventricular tachycardia may be evoked and specific therapy for this abnormality is associated with remission of syncope. In contrast, electrophysiologic studies in patients with no underlying cardiac disease have a very low yield of abnormal findings in the order of 10–20%, and should be performed only when there are reasons to suspect the presence of arrhythmias. Furthermore, in patients with no underlying cardiovascular disease there is a high spontaneous remission rate of syncope and the late incidence of sudden death is low, and related to the presence of other systemic illnesses. At present, the significance of nonsustained ventricular tachycardia or ventricular fibrillation induced during cardiac electrophysiologic studies in patients with no documented arrhythmias is unknown, and further prospective studies are necessary to define appropriate therapy for these patients. Further investigation is also required to clarify the spontaneous remission rate of syncope, as this information is of vital importance in assessing the success of any therapeutic modality.

Research paper thumbnail of Controlled Cryothermal Injury to the AV Node: Feasibility for AV Nodal Modification

Pace-pacing and Clinical Electrophysiology, 1985

Elective subtotal injury to the AV node-His bundle region may create a negative dromotropic effec... more Elective subtotal injury to the AV node-His bundle region may create a negative dromotropic effect to provide a therapeutic advantage in some patients with supraventricular tachycardia without creating complete AV block. We examined the effects of cryosurgery to the AV nodal region, varying temperature and time using a 15 mm circular cryoprobe applied directly to the canine AV node-His bundle region. Twelve dogs were anesthetized and the heart was exposed through a right thoracotomy. Electrophysiological data obtained included conduction intervals, incremental pacing, and extrastimulus testing. Under inflow occlusion, the cryoprobe was positioned over the AV node-His bundle region using anatomical landmarks and a single freeze was applied (–15°C to –60°C, 15 to 60 seconds). Dogs were allowed to recover for 1 month, after which time electrophysiological testing was repeated under similar conditions; then the animals were sacrificed. With probe temperatures of –60°C for 15 to 60 seconds, five of six dogs experienced complete heart block with dense fibrosis observed in the AV nodal-His bundle region. After freezing with higher temperatures, the remaining seven dogs had return of atrioventricular conduction postoperatively with prolongation of AH time observed in five and marked prolongation of the Wenckebach cycle length in three of the five. We conclude that controlled cryothermal injury to the AV node-His bundle region may be useful to create a desirable negative dromotropic response without creating complete AV block.

Research paper thumbnail of Effects of lidocaine and verapamil on defibrillation in humans

Journal of Electrocardiology, 1991

Patients with automatic dehbrillators frequently require chronic antiarrhythmic drug therapy or r... more Patients with automatic dehbrillators frequently require chronic antiarrhythmic drug therapy or receive acute therapy with the onset of symptoms. The effects on energy requirements for defibrillation of lidocaine hydrochloride and verapamil hydrochloride, two commonly used antiarrhythmic agents, were examined in 20 successive patients undergoing corrective arrhythmia surgery. The minimum energy requirement for ventricular defibrillation before and 5 minutes after the administration of 150 mg of lidocaine intravenously (n = 8), or 10 minutes after 10 mg of verapamil intravenously (n = 12), were determined. Each patient was assigned to receive either verapamil or Iidocaine. Three mesh coil defibrillating electrodes (Medtronic 6891, 6892) were sutured to the epicardium of the right and left ventricles. Ventricular fibrillation was induced using alternating current. After a minimum of 10 seconds of fibrillation, the minimum energy for defibrillation was established using sequential pulse defibrillation. The preselected drug was then infused and the ventricular defibrillation energy was again determined after 5 or 10 minutes circulation time. Lidocaine did not alter the minimum energy for defibrillation (3.0 _' I.4 J vs. 3.0 k 1.8 J, mean k SD), despite plasma levels of lidocaine that averaged 13.2 t I.9 pmol/l. In contrast, verapamil significantly increased (3.9 k 2.2 J vs. 6.5 2 2.9 J) the minimum energy necessary for defibrillation. The difference in defibrillation energy was significantly correlated to the fall in systolic blood pressure induced by verapamil administration (r = 0.72). These data reinforce the necessity for determining efficacy of defibrillation when medication changes are instituted. Verapamil should be used with caution in patients with automatic deiibrillators and marginal defibrillation threshold.

Research paper thumbnail of Termination of acute atrial fibrillation in the Wolff-Parkinson-White syndrome by procainamide and propafenone: Importance of atrial fibrillatory cycle length

Journal of The American College of Cardiology, 1990

The effects of intravenous procainamide (n = 30) or prepotentate (n = 25) were evaluated in 55 pa... more The effects of intravenous procainamide (n = 30) or prepotentate (n = 25) were evaluated in 55 patients with acute .trial fibrillation and the Wolff-Pi rkinson-White syndrome. All patients received either procainamide (12 to 15 mg)kg body weight) or propafenone (I to 2 mglkg) during sustained (>10 min) atria) fibrillation or after termination of nonsustatned atria) fibrillation. Termination of atrtut fibrillation was attributed to a drug if it occurred -15 min after infusion . Measurements included mean cycle length of fibritlatory electrograms (mean AA interval) as measured at the high right atrium and shortest RR Interval between pre-excited cycles during atriai fibrillation.

Research paper thumbnail of Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome

Pace-pacing and Clinical Electrophysiology, 1989

SZABO, T.S., et al.: Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome Ope... more SZABO, T.S., et al.: Localization of Accessory Pathways in the Wolff-Parkinson-White Syndrome Operative and ablative therapy in the Wolff-Parkinson-White syndrome requires accurate localization of accessory atrioventricular pathways. A reasonable first approximation to pathway location can be obtained by noninvasive techniques, the 12-lead electrocardiogram being the most readily available of these. Accurate characterization of the number and anatomic localization of accessory pathways still requires invasive electrophysiological assessment. The most useful technique for accessory pathway localization remains endocardial atrial mapping of the tricuspid and mitral (via the coronary sinus) ring during atrioventricular reciprocating tachycardia and ventricular pacing. Other techniques provide important confirmatory evidence and may be the only guides to accessory pathway location in selected individuals.

Research paper thumbnail of Results of operative therapy in the permanent form of junctional reciprocating tachycardia

American Journal of Cardiology, 1989

To assess the results of operative therapy for permanent junctional reciprocating tachycardia, a ... more To assess the results of operative therapy for permanent junctional reciprocating tachycardia, a type of incessant tachycardia, the ctintcal and electrophysiologic data of 8 such patients referred for management of tachycardia were reviewed. The duration of incessant tachycardia was 14 f 10 years (range 2 to 30). The heart rate at rest during tachycardia ranged from 120 to 150 beats/min. Pour of S patients had cardiomegaly or depressed ejection fraction (16 f lo%, range 5 to 27) at pre sentation and, of these, 2 had symptoms of congestive heart failure. Exertional dyspnea despite normal left ventricular function Was noted in 1 patient, 2 had chronic palpitations and 3 were asymptomatic. Electrophysiologic data confirmed the presence of a posteroseptal pathway with atrioventricular node-like properties conducting slowly in the retrograde direction only.