Modulation of procainamide's effect on conduction by cellular uncoupling in perfused rabbit hearts.

INTRODUCTION: How cell-to-cell electrical coupling influences an antiarrhythmic agent's effect on conduction is largely unknown. To investigate this, we evaluated the effects of procainamide on myocardial conduction at decreasing degrees of cell-to-cell electrical coupling induced by graded doses of heptanol. METHODS AND RESULTS: Electrograms were recorded from 50 ventricular epicardial sites in a 1 cm x 0.5 cm area during pacing to produce conduction longitudinal or transverse to myocardial fiber orientation in Langendorff-perfused rabbit hearts. The effects of procainamide (15 mg/L) on conduction velocity were determined in the presence of increasing doses of heptanol (0.2, 0.5, and 1.0 mM). In addition, using standard microelectrode techniques in isolated superfused rabbit myocardium, intracellular potentials were recorded in the presence of 15 mg/L procainamide and heptanol (1.0 mM). In the absence of heptanol, procainamide slowed conduction velocity. In the presence of increasing doses of heptanol, procainamide's contribution to the depressant effect on conduction velocity was attenuated and reversed at the highest dose. The latter effect was preferentially seen for conduction longitudinal to myocardial fiber orientation. Heptanol had no effect on action potential amplitude or maximum rate of depolarization in the presence of procainamide. CONCLUSIONS: Procainamide's effect on conduction velocity is influenced by the underlying degree of cell-to-cell electrical coupling. The present model should be useful in evaluating the relative ability of other pharmacologic agents to modulate conduction under conditions of changing cell coupling.

Effect of bundle branch block on local electrogram morphologic features: implications for arrhythmia diagnosis by stored electrogram analysis.

Analysis of stored local ventricular electrogram recordings is a useful diagnostic tool in the evaluation of patients with implantable cardioverter defibrillators. Visual analysis of local electrogram morphologic features has been demonstrated to be useful in distinguishing ventricular tachycardia from supraventricular rhythm. The effect of bundle branch block (BBB) aberration during supraventricular tachycardia on local electrogram morphologic features is not entirely clear. Erroneous diagnoses resulting from a change in electrogram morphologic features with BBB may occur. To determine whether the development of BBB can produce a change in local electrogram morphologic features and whether this change is dependent on the site of recording, we retrospectively reviewed local electrogram recordings from 23 patients who had intermittent BBB during electrophysiologic evaluation of documented or suspected supraventricular tachycardia. Local electrogram recordings from catheters placed in the right ventricular apex and coronary sinus during supraventricular tachycardia with BBB aberrancy were compared with recordings during narrow complex supraventricular tachycardia or normal sinus rhythm. Bipolar recordings were made with a 5 mm interelectrode distance with filter settings at 40 to 400 Hz. Three independent blinded observers defined the paired electrograms as the same or distinctly different. During right BBB a change in electrogram morphologic features was demonstrated in 11 (85%) of 13 recordings from the right ventricular apex and in only 1 (8%) of 12 recordings from the coronary sinus. In contrast, during left BBB a change in electrogram morphologic features was seen in 6 (100%) of 6 recordings from the coronary sinus and in only 1 (8%) of 13 recordings from the right ventricular apex. These results demonstrate that when the described recording techniques are used, a change in local ventricular electrogram morphologic features BBB is predominantly manifest in recording sites ipsilateral to the BBB, whereas recording sites contralateral to the BBB are relatively unaffected. This information may have implications regarding interpretation of stored electrograms when an attempt is made to establish a rhythm diagnosis leading to implantable cardioverter defibrillator therapy.

Efficacy of antitachycardia pacing in patients presenting with cardiac arrest.

The efficacy of antitachycardia pacing (ATP) incorporated into implantable cardioverter defibrillators (ICDs) was assessed in 29 consecutive survivors of cardiac arrest, not attributable to acute myocardial infarction, ischemia, or drug and electrolyte effects. The cohort included 25 men and 4 women with a mean age of 65 years and a mean left ventricular ejection fraction of 29%. Seventeen patients had coronary artery disease, 11 had nonischemic dilated cardiomyopathy, and 1 had long QT syndrome. Programmed stimulation yielded monomorphic ventricular tachycardia (VT) in 17 patients, polymorphic VT in 6, and no inducible VT in 6. During a mean follow-up of 22 months, a total of 91 episodes of monomorphic VT occurred, 73 of which were successfully pace terminated (83%). Monomorphic VT amenable to pace termination recurred only in the group that had this arrhythmia inducible. The recurrent arrhythmias in the 12 patients having either no inducible VT or polymorphic VT were all rapid VTs, having a cycle length < 220 ms; and therefore, not amenable to pace termination. These results suggest that ATP incorporated into ICDs is useful in survivors of cardiac arrest and may significantly reduce the number of shocks that these patients would otherwise receive. Programmed stimulation may also help to define those patients who would receive the maximum benefit from ATP.

Characterization of return cycle responses predictive of successful pacing-mediated termination of ventricular tachycardia.

OBJECTIVES: The purpose of this study was to characterize response patterns during overdrive pacing that predict successful termination of ventricular tachycardia. BACKGROUND: Overdrive pacing during ventricular tachycardia typically results in entrainment at slow pacing rates and in termination or acceleration at faster rates. The factors that determine the critical paced cycle length that results in tachycardia termination have not been extensively studied. METHODS: Ventricular tachycardias in 14 patients with coronary artery disease were studied with overdrive pacing at several cycle lengths. Return cycles were measured after each additional paced beat at each paced cycle length. The return cycle responses during pacing trials that resulted in tachycardia termination and those that resulted in entrainment were compared. RESULTS: Three return cycle responses were identified: flat, plateau and increasing. Twenty trials of overdrive pacing resulted in tachycardia termination; all were characterized by an increase in the return cycle with the delivery of each successive beat in the pacing drive until the tachycardia terminated (increasing response). Thirty-four pacing trials resulted in entrainment and not termination; these were characterized either by a constant return cycle (flat response) or an initial increase in return cycle followed by a longer, constant return cycle (plateau response) with the delivery of additional paced beats. The longest paced cycle length that resulted in tachycardia termination correlated with the relative refractory period of the circuit, defined as the tachycardia cycle length minus the fully excitable gap (r2 = 0.764, p = 0.0001). Tachycardia termination was not observed unless the paced cycle length was shorter than the relative refractory period of the circuit. CONCLUSIONS: The critical paced cycle length that causes termination of ventricular tachycardia depends on the relative refractory period of the circuit because this factor determines whether the nth + 1 beat of the pacing drive will encounter partially recovered tissue. These data provide insights into the mechanism of pacing-mediated tachycardia termination and entrainment and are applicable to the development of improved antitachycardia pacing algorithms.

Effectiveness of noninvasive programmed stimulation for initiating ventricular tachyarrhythmias in patients with third-generation implantable cardioverter defibrillators.

Previous generations of implantable cardioverter defibrillators (ICDs) required invasive electrophysiological testing to assess defibrillator function. Newer third-generation ICDs include the capability for performing noninvasive programmed stimulation (NIPS) and may reduce the need for invasive studies to assess tachycardia recognition and antitachycardia therapy algorithms. The effectiveness of ICD-based NIPS for the induction of ventricular arrhythmias has not, however, been formally assessed. Third-generation ICDs were implanted in 79 patients, who underwent a total of 166 postoperative defibrillator tests. NIPS with rapid ventricular pacing was performed in all patients in an attempt to induce ventricular fibrillation. In patients with prior sustained uniform ventricular tachycardia, programmed stimulation with up to three extrastimuli was performed in order to attempt to initiate the clinical ventricular tachcardia. Ventricular fibrillation was induced with NIPS in 146 of 166 studies (88%). Ventricular tachycardia was initiated with NIPS in 104 of 123 studies (85%). The type of defibrillator and the use of endocardial or epicardial rate sensing/pacing leads did not influence the efficacy of NIPS. NIPS with third-generation ICDs is generally effective at inducing ventricular fibrillation and clinically relevant ventricular tachycardias, and reduces the need to perform invasive electrophysiological testing following device implantation. In a minority of patients temporary transvenous pacing catheters must still be used to facilitate arrhythmia induction.

Unique sensing errors in third-generation implantable cardioverter-defibrillators.

OBJECTIVES: Third-generation cardioverter-defibrillators appear to be susceptible to unique sensing errors. This study was performed to determine the incidence and types of sensing errors in combination therapy implantable devices. BACKGROUND: One of the advantages offered by third-generation implantable cardioverter-defibrillators is the combination of bradycardia and antitachycardia pacing and cardioversion-defibrillation capabilities in a single device. The potential for unique sensing errors, those caused by the conflicts presented by combining bradycardia and tachycardia sensing and therapy algorithms in the same device, has not been previously addressed. METHODS: To determine the incidence of important sensing errors, 61 patients with a combination therapy device (Cadence [Ventritex] and PCD [Medtronic]) were studied for a 25-month period. In addition to surface electrocardiographic recordings during implantation and routine device testing, real-time and stored electrograms recorded from the rate-sensing leads (Cadence) and real-time marker channel recordings (PCD) were reviewed to diagnose sensing errors that resulted in symptoms, device inefficacy or delivery of inappropriate therapy. After recognition, specific reprogramming steps were performed in an attempt to avoid recurrent sensing errors. RESULTS: A total of 13 sensing errors were diagnosed in 12 patients (19.7%); the incidence was similar in both devices. Five distinct categories of sensing errors were identified. After device reprogramming, only one recurrent error occurred in 98 patient-months of follow-up. CONCLUSIONS: Important sensing errors occur in approximately 20% of patients with third-generation combination therapy cardioverter-defibrillators. Prompt diagnosis of sensing errors can lead to specific reprogramming steps to avoid recurrent errors.

Effect of rate and coupling interval on endocardial R wave amplitude variability in permanent ventricular sensing lead systems.

OBJECTIVES: We have observed sensing errors in third generation implantable cardioverter-defibrillators that appear to be caused by variation in the R wave amplitude during sinus rhythm, particularly after premature beats. The purpose of this study was to quantify spontaneous R wave variability during sinus rhythm and to determine whether abrupt changes in cycle length further augment R wave amplitude variability. BACKGROUND: Pacemaker sensing algorithms presume a relatively constant R wave signal to establish a sensing threshold. The concept of a fixed sensing threshold is not as applicable in third-generation cardioverter-defibrillators, which depend on automatic gain amplifiers to rapidly detect ventricular fibrillation. These devices may be susceptible to undersensing during sinus rhythm if significant variability in R wave signal characteristics occurs. METHODS: Twelve patients with combination bradycardia pacing cardioverter-defibrillators were studied. The device used (Cadence, Ventritex) allowed recording of real time, telemetered electrograms from the sensing lead system. Measurements were made of the maximal range of the R wave amplitude during sinus rhythm and in response to abrupt changes in heart rate produced by premature atrial and ventricular stimuli. RESULTS: The maximal range in R wave amplitude during sinus rhythm was 1.7 +/- 1.3 mV, or 23.7 +/- 19.2% of the mean R wave amplitude. The R wave amplitude variability increased with abrupt changes in cycle length, with a range of 2.8 +/- 1.5 mV, or 38.8 +/- 18.3% of the mean R wave amplitude (p < 0.05 compared with sinus rhythm). In most patients, R wave amplitude and coupling interval demonstrated an inverse proportional relation. CONCLUSIONS: There is substantial variability in the R wave amplitude during sinus rhythm measured by permanent ventricular sensing lead systems, and this variability is further augmented by abrupt changes in cycle length. This phenomenon may explain the occurrence of undersensing of sinus rhythm in implantable cardioverter-defibrillators with automatic gain sense amplifiers.

Implantable cardioverter-defibrillator therapy in the absence of significant symptoms. Rhythm diagnosis and management aided by stored electrogram analysis.

BACKGROUND: This report describes the value of stored ventricular electrogram analysis in the diagnosis and management of patients experiencing minimal or no symptoms before implantable cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS: The study population included 48 patients who received the Cadence Tiered Therapy Defibrillator System, an investigational third-generation ICD with ventricular electrogram storage capabilities. Criteria for arrhythmia diagnosis were based on analysis of the electrogram rate, RR interval variability, and morphology. Twenty-nine of the 48 patients (60%) experienced at least one episode of antitachycardia pacing or shock (one shock or more in 25 of 29 patients) that was preceded by minimal or no symptoms during a mean follow-up of 15.1 +/- 7.8 months. There were 194 tachycardia episodes registered by the device, including 101 for which ventricular electrograms were stored and available for analysis. Of the 101 stored electrograms, 74 were classified as ventricular tachycardia (VT), 24 as non-VT rhythms (atrial fibrillation, 13; supraventricular tachycardia, six; rate-sensing lead disruption, four; T wave oversensing, one), and only three as indeterminate rhythms. Based on the electrogram analysis, changes in tachycardia detection criteria and/or antiarrhythmic drug regimens were implemented and were associated with a reduction in the number of device responses for non-VT rhythms from 24 during the initial study period to three during 11.0 +/- 7.2 months of additional follow-up. CONCLUSIONS: ICD responses in the absence of symptoms are relatively common in third-generation devices with antitachycardia pacing capabilities. Despite potential limitations such as the effect of bundle branch block on the electrogram morphology during supraventricular tachycardia, the availability of electrogram storage capabilities allowed a presumptive diagnosis of the events precipitating asymptomatic device responses. Device reprogramming based on analysis of stored electrograms was associated with a dramatic reduction in the incidence of ICD responses for non-VT rhythms.

Comparison of resetting and entrainment of uniform sustained ventricular tachycardia. Further insights into the characteristics of the excitable gap.

BACKGROUND: Resetting and entrainment have both been used to characterize the electrophysiological properties of the reentrant circuit in ventricular tachycardia. Several entrainment studies have suggested that the circuit has decremental properties, because the return cycle increases at faster pacing rates. Resetting, however, demonstrates a fully excitable gap in the majority of tachycardias. METHODS AND RESULTS: The response to resetting and overdrive pacing was analyzed in 18 ventricular tachycardias. Resetting demonstrated some duration of a fully excitable gap in 14 of 18 tachycardias. Overdrive pacing was performed at several cycle lengths with an incremental number of stimuli (1-15 beats) such that the first beat that interacted with the tachycardia (the nth beat) could be identified. The return cycles measured during resetting and the nth beat of pacing were identical (r = 0.99). At relatively long paced cycle lengths, paced beats after the nth beat resulted in a constant return cycle in most tachycardias with a fully excitable gap. At rapid paced cycle lengths, an increase in the return cycle from the nth to the nth + 1 beat was associated with progressive prolongation in the return cycle with each incremental paced beat until a longer equilibrium return cycle was reached or the tachycardia terminated in response to pacing. CONCLUSIONS: We propose that the responses to resetting and overdrive pacing with or without entrainment appear to provide conflicting information about the characteristics of the circuit because they in fact measure entirely different electrophysiological parameters. The nth beat of pacing foreshortens the excitable gap to the extent that it arrives prematurely. Subsequent paced beats interact with an altered tachycardia circuit that has had less time to recover excitability. Resetting is the interaction of a single paced beat with the tachycardia and, as such, provides a more accurate assessment of the characteristics of the unaltered tachycardia circuit.

Importance of abortive shock capability with electrogram storage in cardioverter-defibrillator devices.

OBJECTIVES: This study evaluates the ability of a third-generation cardioverter-defibrillator to abort energy delivery and the importance of electrogram storage in analyzing the aborted events. BACKGROUND: In the Cadence Tiered Therapy Defibrillator, when a tachycardia satisfies detection criteria for cardioversion or defibrillation therapy, high voltage capacitors begin charging. The Cadence defibrillator continues monitoring the rhythm during charging and if the rate decreases to below the rate triggering therapy, charging is terminated. This event is registered as an aborted shock. The defibrillator also has the ability to store intracardiac electrogram recordings of the electrical events that precipitate device therapy or aborted shocks. METHODS: During a mean follow-up interval of 10 +/- 7 months, 55 aborted events were registered by the Cadence defibrillator in 18 of the 49 patients who received it. Thirty-two stored ventricular electrograms of events leading to aborted shocks were available for analysis in 15 patients. RESULTS: Intracardiac electrogram recordings demonstrated the probable electrical events leading to these aborted shocks included nonsustained ventricular tachycardia (n = 10), nonsustained rapid polymorphic ventricular tachycardia/ventricular fibrillation (n = 2), atrial fibrillation (n = 5), supraventricular tachycardia (n = 2) and electrical noise (n = 13). Eleven patients had a therapeutic intervention initiated as a consequence of the diagnostic information provided by analysis of intracardiac electrogram recordings. Four of the 15 patients had no changes made. During a follow-up period of 9 +/- 5 months after therapy was altered, no patient had subsequent aborted shocks. Five patients have had seven appropriate shocks for sustained ventricular tachycardias. CONCLUSIONS: The ability of Cadence defibrillator to continue tachycardia sensing during capacitor charging and to abort shock therapy for self-terminating events prevented unnecessary shocks in 18 (37%) of the 49 patients. Intracardiac electrogram recordings were critical for instituting appropriate therapy that may have prevented unnecessary device charging and inappropriate discharges.

Effect of coronary perfusion of heptanol or potassium on conduction and ventricular arrhythmias.

Abnormalities in cellular coupling, modulated in part by intracellular gap junctions, have an important role in the genesis of reentrant arrhythmias in the setting of chronic myocardial infarction. The effects of heptanol, which has a relatively selective action on gap junctional resistance at low concentrations, and potassium, which primarily affects active membrane properties, were assessed using a localized intracoronary infusion system in 11 normal dogs in vivo. Both agents caused a dose-related slowing of conduction. Programmed stimulation during potassium infusion resulted in ventricular fibrillation in two of six animals treated with a low dose (5.0-5.5 meq/l) and five of six animals treated with a high dose (7.0-7.5 meq/l). During the infusion of 1.0 mM heptanol, uniform ventricular tachycardia was induced in four of eight animals. Infusion of heptanol, but not potassium, increased the susceptibility to presumably reentrant ventricular tachycardia in normal myocardium. This suggests that agents that affect cellular coupling may have markedly different arrhythmogenic consequences than agents that primarily alter active membrane properties.

Acute and chronic cycle length dependent increase in ventricular pacing threshold.

Several factors have been shown to influence ventricular pacing threshold in humans, including pacing lead location (endocardial vs epicardial), lead maturation, and antiarrhythmic agents. To determine whether ventricular pacing rate has a significant influence on acute and chronic pacing thresholds, we measured pacing thresholds in 16 patients receiving an implantable antitachycardia pacemaker cardioverter defibrillator (Cadence). Ventricular pacing thresholds were determined using the device programmer at cycle lengths of 600, 400 and 300 msec at the time of implantation; prior to hospital discharge at 3-14 days; and during follow-up outpatient visits at 6-8 weeks, 3 months, and 6 months to 1 year. Eleven patients had an epicardial lead system and five an endocardial lead system. Eleven patients were being treated with antiarrhythmic drug therapy. Device output ranged from 1-10 V and was adjustable in 1-V increments (pulse width was held constant at 1 msec). A cycle length dependent increase in pacing threshold (defined as a > or = 1-V increase in threshold at 400 or 300 msec relative to 600 msec) was observed in 10/16 patients during 12/72 pacing trials at 400 msec, and in 15/16 patients during 31/67 trials at 300 msec. In trials in which an increase in pacing threshold occurred, the magnitude of the increase at 400 msec relative to 600 msec was only 1 V in all 12 trials, but at 300 msec the increase ranged from 4-9 V in 7/31 (23%) trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of high-current stimulation in patients with sustained ventricular tachycardia rendered noninducible by antiarrhythmic drugs.

Successful antiarrhythmic drug therapy for sustained ventricular tachycardia (VT) is presumed to be related to effects on myocardium within the re-entrant circuit. To test the hypothesis that prevention of VT induction may be related to effects on myocardium other than that directly involved in the tachycardia circuit, high-current stimulation was used to achieve shorter coupling intervals in 22 patients with sustained uniform VT that was rendered noninducible by antiarrhythmic agents during stimulation at twice threshold. Sustained uniform VT was induced in 10 patients in response to high-current stimulation (group 1), including 4 tachycardias with the same morphology observed in the baseline study. There were no inducible arrhythmias in 12 patients (group 2). Patients were receiving several different antiarrhythmic regimens, but there was no particular drug associated with the induction of VT using high-current stimulation. There was no statistically significant difference between groups 1 and 2 in baseline VT cycle length (247 +/- 41 vs 253 +/- 44 ms), drug-induced increase in effective refractory period (20 +/- 15 vs 16 +/- 7%), QRS duration (25 +/- 10 vs 20 +/- 17%) or maximal current strength delivered (10.9 +/- 5.3 vs 9.3 +/- 4.0 mA). There was no significant difference in local activation with high-current stimulation between groups 1 and 2. In conclusion, sustained uniform VT was induced in 45% (10 of 22) of patients whose arrhythmias were rendered noninducible by antiarrhythmic agents during programmed stimulation at twice threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of electrophysiological testing and long-term follow-up in patients sustaining cardiac arrest only while receiving type IA antiarrhythmic agents.

UNLABELLED: Therapeutic management of patients sustaining a cardiac arrest while receiving antiarrhythmic agents can be difficult since the role of the drug in possibly facilitating the arrhythmia is often difficult to define. To determine if the response to programmed stimulation could give insight into which patients may have experienced a drug-induced cardiac arrest, we studied 29 patients (61 +/- 9 years) with no prior history of sustained ventricular tachyarrhythmias (VT) who suffered a cardiac arrest only while receiving type Ia antiarrhythmic agents. Patients with documented myocardial infarction, acute ischemia, electrolyte abnormalities, or torsade de pointes were excluded from the study. Twenty-four patients had coronary artery disease with prior myocardial infarction (ejection fraction 28% +/- 9%) and five patients had idiopathic dilated cardiomyopathy (ejection fraction 31% +/- 6%). During baseline electrophysiological testing, 19 patients (66%) had inducible sustained ventricular arrhythmias: uniform VT, n = 14 (group I), polymorphic VT or ventricular fibrillation, n = 5 (group II). Ten patients (group III) had no inducible sustained ventricular arrhythmias. To determine if rechallenge with a type Ia agent could facilitate induction of a sustained ventricular arrhythmia in group III, eight patients underwent ten electrophysiological studies during therapy with either procainamide or quinidine. Only two patients developed sustained VT in response to programmed stimulation. Patients in groups I and II received therapy guided by electrophysiological testing, including antiarrhythmic agents alone (n = 8), subendocardial resection (n = 4), or an implantable cardioverter defibrillator (n = 7). Patients in group III received antiarrhythmic agents empirically (n = 3), or for treatment of atrial tachyarrhythmias (n = 2) or nonsustained VT (n = 1). In addition, four patients in group III received an implantable cardioverter defibrillator. During a mean follow-up of 28 +/- 27 months (range: 1 day-84 months) 13 patients died suddenly or received a defibrillator shock preceded by syncope or presyncope: group I: n = 5; group II: n = 2; group III: n = 6. IN CONCLUSION: (1) most patients sustaining a cardiac arrest only in the presence of type Ia antiarrhythmic agents have inducible sustained VT in the absence of antiarrhythmic agents, and (2) the risk of recurrent VT persists in patients without inducible sustained arrhythmias in the drug-free state, regardless of whether they manifest inducible arrhythmias after rechallenge with a type Ia agent.

The mechanism of propafenone-induced slowing of ventricular tachycardia in man as defined by analysis of resetting response patterns.

The major finding in this study was that all VTs in patients treated with propafenone had a fully excitable gap. As only well tolerated, uniform VT in patients with chronic coronary artery disease was included for study, this result may not apply for ventricular arrhythmias in other patient populations. This is incompatible with the hypothesis that propafenone slows VT by increasing refractoriness within the VT circuit. Instead, the drug-mediated prolongation in VT cycle length is caused by effects on conduction velocity in fully recovered tissue and/or a change in the barriers of the circuit.

Paced beats following single nonsensed complexes in a "codependent" cardioverter defibrillator and bradycardia pacing system: potential for ventricular tachycardia induction.

Patients with implantable defibrillators often require bradycardia pacemakers. Adverse interactions between separate defibrillator and bradycardia pacing units have occurred, including failure to detect ventricular fibrillation due to persistent bradycardia pacing during the arrhythmia. A device with combined bradycardia pacing and antitachycardia therapy capability may obviate adverse device interactions. We describe a previously unrecognized phenomenon that may occur in a combined device when the algorithms for sensing bradycardia and tachycardia are "codependent"; that is, the circuitry for brady- and tachyarrhythmia detection relies on the same automatic gain sense amplifier. Three of 37 patients in whom the device was implanted had ventricular tachycardia initiated when bradycardia pacing stimuli were delivered by the device after probable nonsensed sinus beats. In each case, nonsensed beats appeared to have a markedly diminished amplitude, occurred after ventricular premature depolarizations that produced large amplitude electrograms, and had an electrogram morphology that matched that of sinus rhythm. In each case, the bradycardia pacing interval was at least 1,200 msec (range 1,200 to 1,714 msec). In two of the three patients, large amplitude ventricular premature depolarizations or nonsustained ventricular tachycardia caused an adjustment of the gain control that potentiated the failure to sense the subsequent lower amplitude signal. In all three patients, the induced arrhythmia was rapidly terminated by pacing or cardioversion. Decreasing the bradycardia pacing interval by 110-514 msec has prevented recurrence during short-term follow-up. Our findings suggest that codependent bradycardia and antitachycardia devices may have their own unique potential difficulties in adapting to rapid changes in rate and signal amplitude.

Which cardiac disturbances should be treated with digoxin immune Fab (ovine) antibody?

Digoxin excess can produce characteristic bradyarrhythmias, tachyarrhythmias, and hyperkalemia. The bradyarrhythmias, which consist of disturbances in conduction and block at the level of the atrioventricular and sinus nodes, are mediated by a direct and vagotonic effect. The vagotonic effect of excess digoxin may also result in a marked slowing of the sinus rate in the setting of severe toxicity. Digoxin increases automatic and triggered electrical activity in atrial muscle, His-Purkinje system, and ventricular muscle, which predisposes to tachycardias. Many of the tachyarrhythmias are relatively specific for the toxic effects of digoxin. Atrial tachycardias with variable atrioventricular block, accelerated junctional rhythms (especially in the setting of atrial fibrillation), and fascicular tachycardias are characteristic digoxin toxic rhythms. Digoxin-specific antibody fragments should be considered the treatment of choice for any digoxin toxic arrhythmia associated with hemodynamic compromise or the threat of hemodynamic compromise. Hyperkalemia, when due to acute severe digoxin toxicity, is also an appropriate indication for digoxin-specific Fab fragment therapy. When assessing the risk:benefit ratio for using digoxin-specific Fab fragment therapy, one needs to determine, in addition to the electrocardiographic manifestations and patient's hemodynamic status (1) the severity of toxicity, as indexed by the amount ingested and/or the serum digoxin concentration; (2) the expected time course for reversal of toxicity, which is usually determined by the status of renal function; (3) the need for digoxin to provide ventricular rate control or improved ventricular contractility and therapeutic alternatives to digoxin; (4) the presence of a strong allergy history; (5) the presence of such factors as increased age and severity of heart disease that may predispose to digoxin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of ventricular electrogram recordings in the diagnosis of arrhythmias precipitating electrical device shock therapy.

An antitachycardia pacemaker-cardioverter-defibrillator that is capable of storing ventricular electrograms before and after delivery of device shock therapy was implanted in 16 patients. Three of the patients experienced out-of-hospital device shock therapy preceded by minimal symptoms. Although limitations of electrogram analysis exist and are discussed, careful analysis and registration of electrograms during all supraventricular and ventricular rhythms observed during in-hospital testing served as an important reference for subsequent arrhythmia diagnosis. By analyzing the electrogram rate and RR interval stability and configuration, a definitive diagnosis was established in all three patients (atrial fibrillation, polymorphic ventricular tachycardia and rate-sensing lead disruption, respectively). Thus, the ability to store ventricular electrograms before shock therapy represents a major advance in the management of patients who receive an electrical device to treat ventricular tachyarrhythmia.

Reduction of myocardial infarct size by neutrophil depletion: effect of duration of occlusion.

Experiments were performed in the dog to examine the effects of neutropenia on ultimate infarct size resulting from short (90 minutes) or prolonged (4 hours) circumflex coronary artery occlusion. Sheep antiserum to canine neutrophils was used to produce neutropenia. Control animals received nonimmune serum. Neutrophil infiltration into myocardial infarcts was examined using histopathologic techniques and a semiquantitative scoring system. In 90-minute occlusions with 24-hour reperfusion, neutropenia was associated with the development of significantly smaller infarcts: normopenic group, 43.2% +/- 3.3% (n = 7) vs. neutropenic group, 26.6% +/- 3.7% (n = 10) of the area at risk, means +/- SEM. However, in 4-hour occlusion with 6-hour reperfusion experiments, the tendency of neutrophil depletion to reduce infarct size did not reach statistical significance (46.4% +/- 7.2% vs. 31.5% +/- 6.0% of the area at risk, normopenic vs. neutropenic) despite differences in neutrophil infiltration into the reperfused region. The observed differences in ultimate infarct size could not be attributed to differences in myocardial oxygen consumption. The results suggest that a significant amount of myocardial infarction induced by a limited duration of coronary artery occlusion followed by reperfusion is neutrophil dependent and appears to be less important in determining the fate of myocardium subjected to more prolonged periods of ischemia followed by reperfusion.