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Biomedical subjects

S R Shorofsky

Publications and source records attributed to S R Shorofsky.

At least 19 recordsLinked to original sources

Sensing lead failure in implantable defibrillators: a comparison of two commonly used leads.

INTRODUCTION: Despite major technological advances, structural problems in implantable cardioverter defibrillator (ICD) endocardial sensing leads remain a significant problem. There are two types of ICD sensing leads: (1) dedicated bipolar leads and (2) integrated lead systems that include defibrillation coils. The long-term performance of these two lead systems has not been directly compared. METHODS AND RESULTS: We prospectively examined the incidence of lead failure manifested by inappropriate arrhythmia detection in 247 consecutive patients undergoing abdominal ICD implant at a single center between 1991 and 1995. A total of 107 patients received BT-10 (dedicated bipolar) leads and 140 patients received Endotak (integrated bipolar) leads. Over a mean follow-up of 860 +/- 442 days, there were 19 (17.8%) lead failures with the BT-10 lead (261 to 1,505 days postimplant) compared with only 6 (4.3%; P < 0.01) with the Endotak lead (410 to 1,211 days postimplant). Lead failure was due to an insulation defect in all cases, with the problem occurring in the proximal lead (within the pulse generator pocket) in all but one case. Lead survival was significantly better with the Endotak lead (P = 0.015, risk ratio = 3.0, 95% confidence intervals 1.2 to 7.6). CONCLUSION: Late lead failure due to insulation defects in BT-10 sensing leads (causing inappropriate ICD activation) is a relatively common and progressive phenomenon, with difficulties becoming apparent as long as 4 years after implant. This problem is a likely cause of inappropriate shocks in patients with BT-10 leads. Implantation of a new sensing lead should be considered at the time of elective pulse generator replacement, even in the absence of demonstrable oversensing.

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Optimization of transvenous coil position for active can defibrillation thresholds.

INTRODUCTION: Lead systems that include an active pectoral pulse generator are now standard for initial defibrillator implantations. However, the optimal transvenous lead system and coil location for such active can configurations are unknown. The purpose of this study was to evaluate the benefit and optimal position of a superior vena cava (SVC) coil on defibrillation thresholds with an active left pectoral pulse generator and right ventricular coil. METHODS AND RESULTS: This prospective, randomized study was performed on 27 patients. Each subject was evaluated with three lead configurations, with the order of testing randomized. Biphasic shocks were delivered between the right ventricular coil and an active can alone (unipolar), or an active can in common with the proximal coil positioned either at the right atrial/SVC junction (low SVC) or in the left subclavian vein (high SVC). Stored energies at defibrillation threshold were higher for the single-coil, unipolar configuration (11.2 +/- 6.6 J) than for the high (8.9 +/- 4.2 J) or low (8.5 +/- 4.2 J) SVC configurations (P < 0.01). Moreover, 96% of subjects had low (< or = 15 J) thresholds with the SVC coil in either position compared with 81% for the single-coil configuration. Shock impedance (P < 0.001) was increased with the unipolar configuration, whereas peak current was reduced (P < 0.001). CONCLUSION: The addition of a proximal transvenous coil to an active can unipolar lead configuration reduces defibrillation energy requirements. The position of this coil has no significant effect on defibrillation thresholds.

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Cellular mechanisms of altered contractility in the hypertrophied heart: big hearts, big sparks.

To investigate the cellular mechanisms for altered Ca2+ homeostasis and contractility in cardiac hypertrophy, we measured whole-cell L-type Ca2+ currents (ICa,L), whole-cell Ca2+ transients ([Ca2+]i), and Ca2+ sparks in ventricular cells from 6-month-old spontaneously hypertensive rats (SHRs) and from age- and sex-matched Wistar-Kyoto and Sprague-Dawley control rats. By echocardiography, SHR hearts had cardiac hypertrophy and enhanced contractility (increased fractional shortening) and no signs of heart failure. SHR cells had a voltage-dependent increase in peak [Ca2+]i amplitude (at 0 mV, 1330+/-62 nmol/L [SHRs] versus 836+/-48 nmol/L [controls], P<0.05) that was not associated with changes in ICa,L density or kinetics, resting [Ca2+]i, or Ca2+ content of the sarcoplasmic reticulum (SR). SHR cells had increased time of relaxation. Ca2+ sparks from SHR cells had larger average amplitudes (173+/-192 nmol/L [SHRs] versus 109+/-64 nmol/L [control]; P<0.05), which was due to redistribution of Ca2+ sparks to a larger amplitude population. This change in Ca2+ spark amplitude distribution was not associated with any change in the density of ryanodine receptors, calsequestrin, junctin, triadin 1, Ca2+-ATPase, or phospholamban. Therefore, SHRs with cardiac hypertrophy have increased contractility, [Ca2+]i amplitude, time to relaxation, and average Ca2+ spark amplitude ("big sparks"). Importantly, big sparks occurred without alteration in the trigger for SR Ca2+ release (ICa,L), SR Ca2+ content, or the expression of several SR Ca2+-cycling proteins. Thus, cardiac hypertrophy in SHRs is linked with an alteration in the coupling of Ca2+ entry through L-type Ca2+ channels and the release of Ca2+ from the SR, leading to big sparks and enhanced contractility. Alterations in the microdomain between L-type Ca2+ channels and SR Ca2+ release channels may underlie the changes in Ca2+ homeostasis observed in cardiac hypertrophy. Modulation of SR Ca2+ release may provide a new therapeutic strategy for cardiac hypertrophy and for its progression to heart failure and sudden death.

Animals

Comparison of bipolar and integrated sensing for redetection of ventricular fibrillation.

BACKGROUND: Implantable cardioverter-defibrillator function is critically dependent on reliable sensing of intracardiac signals. Lead systems that use integrated sensing, in which the distal shocking coil is part of both the sensing and shocking pathways, may be prone to undersensing of ventricular fibrillation, especially during redetection after a failed first shock. To assess the effect of endocardial lead system on redetection, we compared a dedicated rate-sensing lead and 2 generations of integrated sensing defibrillator leads with a uniform testing algorithm and pulse generator. METHODS: The study group consisted of 72 patients after implantable cardioverter-defibrillator implantation. Three transvenous rate-sensing leads were evaluated: a standard pacing lead, incorporating true bipolar sensing without ventricular coils, or an integrated shocking and sensing lead (Endotak C) with either 6-mm (60 series) or 12-mm (70 series) spacing between the sensing tip and shocking coil. Redetection was assessed from a failed first shock just below defibrillation threshold. RESULTS: Compared with the dedicated bipolar lead, redetection was prolonged with the 60 series lead (8.3 +/- 3.6 vs 6.6 +/- 2.3 seconds, P =.04). Moreover, prolonged redetection (>8 seconds) was observed in 41% of patients with 60 series leads compared with only 11% with dedicated bipolar leads (P <.01). No significant effects on redetection were noted with an integrated lead with greater spacing between the tip and coil (70 series). CONCLUSIONS: Delayed redetection is frequently noted with an integrated lead with close spacing between the tip and coil. Detailed evaluation of detection and redetection of these leads should be performed at the time of pulse generator replacement.

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Overdrive atrial pacing for conversion of atrial flutter: comparison of postoperative with nonpostoperative patients.

BACKGROUND: Previous studies have reported varying success rates in overdrive pace termination of atrial flutter. We hypothesized that these discrepancies might be caused by differences in study populations. Accordingly, we prospectively compared the success rate of pacing in patients with atrial flutter that occurred after heart surgery with that of patients with atrial flutter from other causes. METHODS AND RESULTS: The study population consisted of 65 consecutive patients referred for pace termination of typical (type I) atrial flutter. Pacing was performed in 30-second bursts, starting at the flutter cycle length, and repeated in 5-ms decrements until normal sinus rhythm or atrial fibrillation occurred. Normal sinus rhythm was restored in 38 (65%) patients. Of 20 patients whose flutter was precipitated by heart surgery, 19 (95%) were successfully pace terminated. In contrast, pace termination was successful in only 47% of the remainder of the population (P <.001). No other clinical parameters were predictive of outcome. CONCLUSIONS: We conclude that overdrive pacing is an effective means of terminating atrial flutter that has occurred after heart surgery. Alternative methods should be considered as the initial therapeutic approach in patients with atrial flutter from other causes.

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Atrial defibrillation with a transvenous lead: a randomized comparison of active can shocking pathways.

OBJECTIVES: The purpose of this study was to compare transvenous atrial defibrillation thresholds with lead configurations consisting of an active left pectoral electrode and either single or dual transvenous coils. BACKGROUND: Low atrial defibrillation thresholds are achieved using complex lead systems including coils in the coronary sinus. However, the efficacy of more simple ventricular defibrillation leads with active pectoral pulse generators to defibrillate atrial fibrillation (AF) is unknown. METHODS: This study was a prospective, randomized assessment of shock configuration on atrial defibrillation thresholds in 32 patients. The lead system was a dual coil Endotak DSP lead with a left pectoral pulse generator emulator. Shocks were delivered either between the right ventricular coil and an active can in common with the proximal atrial coil (triad) or between the atrial coil and active can (transatrial). RESULTS: Delivered energy at defibrillation threshold was 7.1 +/- 6.0 J in the transatrial configuration and 4.0 +/- 4.2 J in the triad configuration (p < 0.005). Moreover, a low threshold (< or = 3 J) was observed in 69% of subjects in the triad configuration but only 47% in the transatrial configuration. Peak voltage and shock impedance were also lowered significantly in the triad configuration. Left atrial size was the only clinical predictor of the defibrillation threshold (r = 0.57, p < 0.002). CONCLUSIONS: These results indicate that low atrial defibrillation thresholds can be achieved using a single-pass transvenous ventricular defibrillation lead with a conventional ventricular defibrillation pathway. These data support the development of the combined atrial and ventricular defibrillator system.

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The effect of shock configuration and delivered energy on defibrillation impedance.

Shock impedance is an important determinant of defibrillation efficacy. Lead configuration, shock polarity, and delivered energy can affect shock impedance, but these variables have not been studied in active can lead systems. The present study was a prospective evaluation of 25 patients undergoing initial transvenous defibrillator implantation. In all patients, a dual coil lead and pectoral emulator were placed and three lead configurations were tested in random order: Lead (distal to proximal coil), unipolar (distal coil to can), and triad (distal coil to can + proximal coil). Shock energies of 0.1- to 15-J shock were evaluated. Impedance increased a mean of 21% as delivered energy was decreased (P < 0.001), an effect independent of lead configuration. At all delivered energies, impedances in the unipolar configuration were about 40% higher than triad, while the lead configuration was about 20% higher than triad (ps < 0.001). Polarity did not affect impedance. These results indicate that transvenous lead configurations and delivered energy, but not polarity, significantly influence shock impedance. The magnitude of the increase of impedance at low energies is independent of the shocking pathway. This effect has important implications for low energy shocks used to terminate atrial fibrillation or ventricular tachycardia.

Atrial Fibrillation

A new defibrillator discrimination algorithm utilizing electrogram morphology analysis.

Inappropriate therapies delivered by implantable cardioverter defibrillators (ICDs) for supraventricular arrhythmias remain a common problem, particularly in the event of rapidly conducted atrial fibrillation or marked sinus tachycardia. The ability to differentiate between ventricular tachycardia and supraventricular arrhythmias is the major goal of discrimination algorithms. Therefore, we developed a new algorithm, SimDis, utilizing morphological features of the shocking electrograms. This algorithm was developed from electrogram data obtained from 36 patients undergoing ICD implantation. An independent test set was evaluated in 25 patients. Recordings were made in sinus rhythm, sinus tachycardia, and following the induction of ventricular tachycardia and atrial fibrillation. The arrhythmia complex is defined as wide if the duration is at least 30% greater than the template in sinus rhythm. For narrow complexes, four maximum and minimum values were measured to form a 4-element feature vector, which was compared with a representative feature vector during normal sinus rhythm. For each rhythm, any wide complex was classified as ventricular tachycardia. For narrow complexes, the second step of the algorithm compared the electrogram with the template, computing similarity and dissimilarity values. These values were then mapped to determine if they fell within a previously established discrimination boundary. On the independent test set, the SimDis algorithm correctly classified 100% of ventricular tachycardias (27/27), 98% of sinus tachycardias (54/55), and 100% of episodes of atrial fibrillation (37/37). We conclude that the SimDis algorithm yields high sensitivity (100%) and specificity (99%) for arrhythmia discrimination, using the computational capabilities of an ICD system.

Algorithms

Intravenous amiodarone suppression of electrical storm refractory to chronic oral amiodarone.

We report the case of an electrical storm in a cardiac arrest survivor with an ICD, in whom chronic oral amiodarone failed to suppress ventricular arrhythmias, and in whom intravenous amiodarone resulted in stability for 6 weeks prior to successful cardiac transplantation. Intravenous amiodarone can be successful in suppressing life-threatening ventricular arrhythmias, even when chronic oral amiodarone is unsuccessful.

Administration, Oral

The effect of procainamide on T wave alternans.

INTRODUCTION: The measurement of microvolt level T wave alternans (TWA) is a technique for detecting arrhythmia vulnerability. Previous studies demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of antiarrhythmic drugs on TWA are unknown. METHODS AND RESULTS: This was a prospective evaluation of intravenous procainamide on TWA in 24 subjects with inducible sustained ventricular tachycardia (VT). Measurements of TWA were performed at baseline in the drug-free state and after procainamide loading (1,204+/-278 mg). Recordings were made in normal sinus rhythm, and during atrial pacing at 100 beats/min and 120 beats/min. The magnitude of TWA in the vector magnitude lead was decreased by procainamide at all heart rates: 0.6+/-0.8 to 0.3+/-0.4 microV in sinus rhythm, 2.0+/-1.6 to 0.7+/-0.7 microV at 100 beats/min, and 3.0+/-2.0 to 1.7+/-1.8 microV at 120 beats/min (P<0.001 by analysis of variance). The sensitivity of TWA for the induction of VT at baseline was 5% in sinus, 60% at 100 beats/min, and 87% at 120 beats/min, while it decreased with procainamide to 5%, 19%, and 60%, respectively. Decreases in TWA in response to procainamide were independent of the antiarrhythmic effects on VT inducibility. CONCLUSIONS: These results indicate that the magnitude of TWA decreases with acute procainamide loading and this effect decreases the sensitivity of TWA for the induction of sustained VT.

Anti-Arrhythmia Agents

Ca2+ sparks triggered by patch depolarization in rat heart cells.

The goal of this study was to examine the relationship between Ca2+ entry through L-type Ca2+ channels and local [Ca2+]i transients (Ca2+ sparks) in single rat cardiac ventricular cells. L-type Ca2+ channels were activated by depolarization of cell-attached membrane patches, and [Ca2+]i was measured simultaneously as fluo 3 fluorescence using laser scanning confocal microscopy. Patch depolarization with Ca2+ as the charge carrier (10 or 110 mmol.L(-1)) significantly increased the probability of the occurrence of Ca2+ sparks (Ca2+ spark rate) only in the volume of cytoplasm located immediately beneath the membrane patch (basal Ca2+ spark rate, 119 Ca2+ sparks.cell(-1).s(-1); patch depolarization Ca2+ spark rate, 610 Ca2+ sparks.cell(-1).s(-1); P<.005). With Ba2+ in the pipette solution (10 mmol.L(-1)), patch depolarization was not associated with an increased Ca2+ spark rate at the position of the pipette or at any other sites distant from the pipette. Therefore, Ca2+ entry and not voltage per se was a necessary event for the occurrence of Ca2+ sparks. Under identical experimental conditions, patch depolarization experiments opened single L-type Ca2+ channels with a single-channel conductance of 19 pS with Ba2+ as the charge carrier. Although single-channel openings could not be resolved when Ca2+ was the charge carrier, ensemble averages yielded an inward current of up to 0.75 pA. The results suggest that voltage-activated Ca2+ entry through one or a small number of L type Ca2+ channels triggers the release of Ca2+ only from the sarcoplasmic reticulum in direct proximity to those L-type Ca2+ channels. The relatively low probability of triggering Ca2+ sparks may have resulted from some alteration of excitation-contraction coupling associated with the technique of the cell-attached patch clamp.

Animals

Alterations in calcium handling in cardiac hypertrophy and heart failure.

There is conflicting data concerning the effects of cardiac hypertrophy and failure on L-type Ca2+ channel density, the amplitude of the intracellular Ca2+ transients, and the characteristics of Ca2+ sparks. These discrepancies are probably due to multiple factors. First, the effects of cardiac hypertrophy on channel expression and cell adaptation are model dependent. Even within the same species, the mechanisms by which cardiac hypertrophy and heart failure are generated (genetic alteration, pressure overload, volume overload, high rate pacing, etc.) influence the results obtained. Second, with many animal models and diseased human hearts, the disease process is not uniformly distributed throughout the myocardium. Third, the effects on L-type Ca2+ channel behavior and SR function clearly depend on the extent of disease expression. Myocardial contractility increases with cardiac hypertrophy whereas it decreases with heart failure. Thus, it is difficult to compare results from different models of hypertrophy and heart failure at different stages of disease. More consistent data is likely to be obtained from longitudinal studies using a single animal model of disease. The challenge before us is to develop animal models that mimic human disease, which can be studied longitudinally during the progression of the disease process. This approach coupled with continued improvement in Ca2+ imaging and a greater understanding of normal E-C coupling, will enable us to identify precisely the abnormalities in E-C coupling that occur with the development of cardiac hypertrophy and heart failure and define the appropriate treatment modalities.

Calcium

Comparison of single- and dual-coil active pectoral defibrillation lead systems.

OBJECTIVES: The purpose of this study was to compare defibrillation thresholds with lead systems consisting of an active left pectoral electrode and either single or dual transvenous coils. BACKGROUND: Lead systems that include an active pectoral pulse generator reduce defibrillation thresholds and permit transvenous defibrillation in nearly all patients. A further improvement in defibrillation efficacy is desirable to allow for smaller pulse generators with a reduced maximal output. METHODS: This prospective study was performed in 50 consecutive patients. Each patient was evaluated with two lead configurations with the order of testing randomized. Shocks were delivered between the right ventricular coil and either an active can alone (single coil) or an active can with the proximal atrial coil (dual coil). The right ventricular coil was the cathode for the first phase of the biphasic defibrillation waveform. RESULTS: Delivered energy at the defibrillation threshold was 10.1+/-5.0 J for the single-coil configuration and 8.7+/-4.0 J for the dual-coil configuration (p < 0.02). Moreover, 98% of patients had low (<15 J) thresholds with the dual-coil lead system, compared with 88% of patients with the single-coil configuration (p=0.05). Leading edge voltage (p < 0.001) and shock impedance (p < 0.001) were also decreased with the dual-coil configuration, although peak current was increased (p < 0.001). CONCLUSIONS: A dual-coil, active pectoral lead system reduces defibrillation energy requirements compared with a single-coil, unipolar configuration.

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The effect of delivered energy on defibrillation shock impedance.

The impedance of internal defibrillator shocks is an important determinant of defibrillation efficacy. To assess the effect of delivered energy on impedance, we studied 97 patients with 4 different lead systems. The lead systems evaluated were two epicardial patches, a hybrid system of a patch and right atrial coil, a dual coil transvenous lead and a transvenous lead with a subcutaneous patch. Impedances were measured for 6 shock energies between 0.1 and 30 J. Shock impedance increased at low energies for all lead systems (p < 0.001), although the rate of increase varied markedly between systems. The energy factor (FE), which is the ratio of impedances for the 0.1 and 10 J shocks, was least for the platinum transvenous lead (1.2 +/- 0.02) and greatest for the titanium hybrid lead (4.2 +/- 0.2). Reversing the polarity of the hybrid lead markedly attenuated the impedance rise. These findings indicate that there is at least a modest rise (20%) of shock impedance at very low delivered energies. The largest increases noted with titanium lead systems are primarily due to polarization. Titanium transvenous leads should be avoided when low energy shocks are utilized such as for the cardioversion of ventricular tachycardia or atrial fibrillation.

Arrhythmias, Cardiac

A comparison of pectoral and abdominal transvenous defibrillator implantation: analysis of costs and outcomes.

Traditionally cardioverter-defibrillator implantation was performed by surgeons under general anesthesia. However, with advances in lead and pulse generator technology, the surgical implantation technique has been simplified and routine pectoral pulse generator placement without general anesthesia is now possible. To assess the economic benefit of pectoral implantation, we analyzed 43 consecutive initial transvenous defibrillator implantations. The patients were grouped according to whether the implant was abdominal by a surgeon in the operating room (n = 23) or pectoral by an electrophysiologist in a laboratory (n = 20). The duration of hospitalization was significantly longer in the operating room than in the laboratory group (8.1 +/- 3.4 vs 5.8 +/- 2.4 days, p = 0.01), which was due primarily to the postoperative stay which averaged 1.9 days longer. Total costs were $40,274 +/- 6,861 for the operating room cohort and $32,546 +/- 3,634 for the lab group (p < 0.001). This reduction was due to a 32% lowering of professional costs and an 18% lowering of facility costs. We conclude that pectoral defibrillator implantation is cost effective and results in significant reductions of hospital stay.

Abdominal Muscles

Inappropriate shocks from implanted cardioverter defibrillators caused by sensing of diaphragmatic myopotentials.

Inappropriate shocks remain one of the major problems associated with the use of implantable cardioverter defibrillators (ICD). We describe 3 patients who had inappropriate shocks due to oversensing of diaphragmatic myopotentials. In all 3, oversensing could be demonstrated during deep inspiration or Valsalva maneuver. The problem was remedied in one by insertion of a separate rate sensing lead in the right ventricular outflow tract, in the second by decreasing the rate of antibradycardia pacing of the ICD, and in the third by decreasing the sensitivity of the ICD. We conclude that the possibility of sensed diaphragmatic myopotentials should be considered at the time of ICD implant so that appropriate preventive measures can be taken.

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Temporal stability of defibrillation thresholds with an active pectoral lead system.

INTRODUCTION: Monophasic defibrillation thresholds rise over time with a variety of lead systems. These chronic changes are attenuated or eliminated by biphasic waveforms, although the effect appears dependent upon the lead system. With the downsizing of pulse generator size to allow for routine pectoral implantation, active can lead systems have now become standard. However, the temporal stability of such lead systems has not been evaluated previously. METHODS AND RESULTS: This study was a prospective assessment of the changes of active pectoral defibrillation thresholds over time. Thresholds were measured at implant, predischarge, and at a mean follow-up of 50 days in 46 patients with a uniform testing protocol and shock polarity. The lead system was a dual-coil Endotak DSP lead with an active pectoral pulse generator. Defibrillation thresholds were 9.9+/-5.5 J at implantation, 8.5+/-6.0 J predischarge, and 7.6+/-5.5 J at follow-up (ANOVA, P = 0.007). Moreover, only two patients developed an increased threshold > 5 J, and no patient had an inadequate safety margin at follow-up. CONCLUSION: These results indicate that active pectoral defibrillation thresholds are stable over the first 2 months postimplantation and question the need for routine serial defibrillation threshold testing.

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Effect of shock polarity on biphasic defibrillation thresholds using an active pectoral lead system.

INTRODUCTION: The downsizing of implantable defibrillator pulse generators has made pectoral placement routine. A further reduction of defibrillation thresholds (DFTs) may simplify implantation defibrillation testing and allow for smaller, lower output pulse generators while maintaining an adequate defibrillation safety margin. One factor that may affect defibrillation efficacy is shock polarity. METHODS AND RESULTS: Sixty consecutive patients undergoing dual-coil, active left pectoral defibrillator implantation were evaluated. Paired, biphasic DFTs were measured in normal (RV apex = cathode) and reverse (RV apex = anode) polarity with order of testing randomized. Reverse polarity conferred a 15% reduction of mean DFTs (8.5 +/- 5.0 J normal, 7.2 +/- 4.6 J reverse polarity, P = 0.02). The effect of polarity appeared most pronounced among the patients with a high DFT (> or = 15 J) resulting in a 31% reduction with reverse polarity (16.7 +/- 2.5 J normal, 11.5 +/- 5.9 J reverse, P = 0.03). CONCLUSION: Reversing shock polarity results in significantly lower biphasic DFTs with an active pectoral lead system, particularly in the subgroup of patients with a high normal polarity threshold. Reversing polarity in these patients may simplify acute defibrillation testing and allow for lower output devices.

Arrhythmias, Cardiac