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Biomedical subjects

S R Shorofsky

Publications and source records attributed to S R Shorofsky.

At least 55 records · Page 3Linked to original sources

Chronic rise in monophasic defibrillation thresholds with a transvenous lead system.

This study was a prospective evaluation of chronic changes of defibrillation thresholds in 31 clinically stable patients with a single transvenous lead, optimal shock polarity, and uniform testing protocol. At a mean follow-up of 273 +/- 146 days, defibrillation thresholds increased 26%, from 13.2 +/- 5.6 J to 17.1 +/- 6:0 J (p < 0.001), and shock impedance increased from 46.2 +/- 7.0 omega to 51.2 +/- 6.2 omega (p < 0.001).

Aged↗

Clinical predictors of transvenous defibrillation energy requirements.

Nonthoracotomy and, more recently, transvenous lead systems have become routine for initial implantable cardioverter-defibrillator (ICD) placement. Previous studies of clinical predictors of nonthoracotomy defibrillation energy requirements evaluated multiple complex lead systems that included subcutaneous patches. However, the predictors of an adequate transvenous defibrillation threshold (DFT) have not been assessed previously. Accordingly, the present study is a prospective evaluation of DFT using a uniform testing protocol in 119 consecutive patients undergoing ICD implantation with a single transvenous lead. For each patient, 38 parameters were assessed including standard clinical, echocardiographic, and radiographic measures. An adequate monophasic DFT (< or =20 J) was achieved in 76% of patients. Multivariable analysis revealed 3 independent factors predictive of a high threshold: preoperative amiodarone use (odds ratio = 5.8, p < or =0.002), echocardiographic measures of left ventricular dilation (odds ratio = 0.47, p < or =0.005) and body size (odds ratio = 0.51, p < or =0.006). Patients receiving amiodarone who also had left ventricular dilation constitute a group at considerable (69%) risk for having a high DFT. In contrast, patients with neither of these risk factors have only an 11% chance of having a high threshold. We conclude that an adequate transvenous DFT can be predicted from simple clinical parameters.

Amiodarone↗

Biphasic waveforms prevent the chronic rise of defibrillation thresholds with a transvenous lead system.

OBJECTIVES: The purpose of this study was to compare chronic changes in monophasic and biphasic defibrillation thresholds using a uniform transvenous lead system and testing protocol. BACKGROUND: Defibrillation thresholds increase over time in patients with nonthoracotomy lead systems. This increase can result in an inadequate chronic defibrillation safety margin and could limit the safety of smaller pulse generators, which have a reduced maximal output. However, previous studies of the temporal changes of defibrillation thresholds evaluated complex lead systems or monophasic shock waveforms, neither of which are used with current technology. METHODS: This study was a prospective, randomized assessment of the effects of shock waveforms on the changes of transvenous defibrillation thresholds over time. Paired monophasic and biphasic thresholds were measured both at implantation and at follow-up (250 +/- 105 days) in 24 consecutive patients who were not receiving antiarrhythmic drugs. The lead system was a dual-coil Endotak C lead, and reverse polarity shocks (distal coil = anode) were delivered. RESULTS: Monophasic defibrillation thresholds increased from (mean +/- SD) 13.7 +/- 6.0 J to 16.8 +/- 6.7 J (p = 0.02), whereas biphasic thresholds were unchanged (10.4 +/- 4.3 J to 10.2 +/- 4.8 J, p = 0.86) in the same patients. Shock impedance chronically increased (47.0 omega to 50.5 omega, p = 0.02) and was unaffected by waveform. CONCLUSIONS: These results indicate that biphasic shocks prevent the chronic increase in defibrillation thresholds with a transvenous lead system.

Atrial Fibrillation↗

Distortion of intracardiac electrograms following defibrillator shocks for atrial tachyarrhythmias.

In three patients with a defibrillator system consisting of a Ventak P2 pulse generator and an Endotak C transvenous lead, we observed distortion of intracardiac electrograms following defibrillator shocks for atrial arrhythmias. There was a transient marked widening of the intracardiac ventricular complexes resembling ventricular tachycardia. This phenomenon should be recognized when evaluating arrhythmic episodes.

Adult↗

Complications associated with pectoral implantation of cardioverter defibrillators. World-Wide Jewel Investigators.

Pectoral placement of ICD pulse generators is now routine after downsizing of these devices. However, the safety of this approach is not well documented. The aim of this study was to evaluate complications in a large cohort of patients undergoing initial pectoral ICD implantation. The subjects for this study were 1,000 consecutive patients receiving a Medtronic Jewel ICD at 93 centers worldwide. Cumulative follow-up for all patients was 634 patient-years, with 64.9% of patients followed for 6 months or longer. The complications evaluated were erosion, pocket hematoma, seroma, wound infection, dehiscence, device migration, lead fracture, and dislodgment. In this series, 1.8% of patients experienced a pocket complication with only 3 (0.3%) erosions and 2 (0.2%) infections. Lead complications were observed in 2.1% of subjects, most commonly early dislodgment of the RV lead. We conclude that pectoral implantation of a downsized ICD system can be performed with a low rate of complications. However, careful attention to anchoring techniques and close early monitoring is important given the 1.7% rate of lead dislodgment that occurred primarily during the first month following implantation.

Cohort Studies↗

Effect of waveform tilt on defibrillation thresholds in humans.

INTRODUCTION: Despite the common use of the implantable cardioverter defibrillator to treat patients with life-threatening ventricular arrhythmias, the mechanism of defibrillation and the optimal waveform for implanted devices are poorly understood. All of the currently available pulse generators deliver exponentially declining pulses that are either automatically or manually truncated to achieve tilts of about 50% to 65%. Although this value was chosen based on experimental animal data, several theoretical models have been developed to describe defibrillation, which raise into question this choice of waveform shape. Accordingly, the present study was designed to test the effect of waveform tilt on defibrillation efficacy in humans. METHODS AND RESULTS: Twenty-three patients undergoing cardioverter defibrillator implantation were studied. Monophasic defibrillation thresholds (DFTs) were measured using a single reversal protocol at 35%, 50%, 65%, and 80% tilts by altering the pulse width of the shock. Mean defibrillation impedance was 41 +/- 6 omega. The DFT, measured by either leading-edge voltage or stored energy, was insensitive to altering the waveform tilt from 50% to 80%, only increasing when the tilt was reduced to 35%. A tilt of 65% yielded the lowest DFT voltage in only 8 of 23 patients. Significantly lower DFTs (> or = 40 V) were obtained using other tilts in seven patients. When the relationship between average current and pulse width was fit with a Weiss-Lapicque model, the data yielded a mean chronaxie of 4.6 +/- 3.0 msec and a rheobase of 4.2 +/- 1.7 A, but considerable patient variability was observed. CONCLUSION: On average, DFTs in humans are insensitive to altering monophasic waveform tilts between 50% and 80%. There is, however, considerable patient variability, raising into question the premise that a single defibrillator waveform tilt is best for all patients.

Aged↗

Complications associated with pectoral cardioverter-defibrillator implantation: comparison of subcutaneous and submuscular approaches. Worldwide Jewel Investigators.

OBJECTIVES: The aim of this study was to compare complications in a large cohort of patients undergoing pectoral cardioverter-defibrillator implantation with a subcutaneous or submuscular approach. BACKGROUND: Pectoral placement of implantable cardioverter-defibrillator (ICD) pulse generators is now routine because of downsizing of these devices. subcutaneous implantation has been advocated by some because it is a simple surgical procedure comparable to pacemaker insertion. Others have favored submuscular insertion to avoid wound complications. These surgical approaches have not been compared previously. METHODS: The subjects for this study were 1,000 consecutive patients receiving a Medtronic Jewel ICD at 93 centers worldwide. Cumulative follow-up for all patients was 633.7 patient-years, with 64.9% of patients followed up for > or = 6 months. The complications evaluated were erosion, pocket hematoma, seroma, wound infection, dehiscence, device migration, lead fracture and dislodgment. RESULTS: Subcutaneous implantation was performed in 604 patients and submuscular implantation in the remaining 396. The median procedural times were shorter for subcutaneous implantation (p = 0.014). In addition, the cumulative percentage of patients free from erosion was greater for subcutaneous implantations (p = 0.03, 100% vs. 99.1% at 6 months). However, lead dislodgment was more common with subcutaneous implantations (p = 0.019, 2.3% vs. 0.5% at 6 months) and occurred primarily during the first month postoperatively. Overall, there were no significant differences in cumulative freedom from complications between groups (4.1% vs. 2.5%, p = 0.1836). CONCLUSIONS: Subcutaneous pectoral implantation of this ICD can be performed safely and has a low complication rate. This approach requires a simple surgical procedure and, compared with the submuscular approach, is associated with shorter procedure times and comparable overall complication rates. However, early follow-up is important in view of the increased lead dislodgment rate.

Aged↗

Effects of an active pectoral-pulse generator shell on defibrillation efficacy with a transvenous lead system.

Transvenous lead systems have become routine for defibrillator implantation. A reduction of pulse generator size has made pectoral placement possible and enabled the pulse generator shell to become an active part of the defibrillation pathway. To directly assess the effect of the addition of an active generator on defibrillation thresholds to a transvenous lead system, we prospectively measured paired, randomized defibrillation thresholds (DFTs) in 21 patients undergoing defibrillator implantation. A dual coil lead (Endotak C, Cardiac Pacemakers, Inc., Guidant Corp., St. Paul, Minnesota) was used with the distal coil as the cathode for all shocks. The DFT was 8.4 +/- 3.2 J with the active shell, compared with 13.1 +/- 6.9 J with the lead alone (p < 0.01). This reduction was greatest in those patients with higher thresholds with the lead-alone configuration and resulted in DFT < or = 15 J with the active shell configuration in all patients. Shock impedance was reduced from 49 +/- 5 to 42 +/- 4 ohms (p < .001), but peak current at defibrillation threshold was unaffected by the addition of the active pectoral shell. We conclude that the addition of an active pectoral shell to a 2-coil transvenous lead system resulted in a marked reduction of defibrillation energy requirements. The uniformly low DFT ( < or = 15 J) observed suggests that an active pulse generator with a 25 J maximum output could be implanted in most patients while maintaining an adequate defibrillation safety margin.

Aged↗

Chronic rise in defibrillation threshold with a hybrid lead system.

Nonthoracotomy leads have become standard for implantable cardioverter-defibrillators (ICD) because of low perioperative morbidity, mortality, and expense. Reported increases in defibrillation thresholds (DFTs) with these lead systems, however, have raised the possibility of an eventual loss of defibrillation efficacy. The mechanism of this increase is unknown. In contrast, defibrillation efficacy of traditional epicardial lead systems has been demonstrated to remain relatively stable. In the present study, we examined the implantation and chronic DFTs in 45 patients with a hybrid system (a high right atrial coil and an extrapericardial patch) that combines elements from both the thoracotomy and nonthoracotomy approach. The mean threshold increased from 11.7 +/- 3.0 to 15.8 +/- 10.0 J (p < 0.001) and mean impedance increased from 37.0 +/- 7.7 to 48.8 +/- 9.0 ohms (p < 0.0001). There was a marked (> or = 10 J) increase in DFT in 11 patients (24%) including 4 who required reoperation to obtain an adequate safety margin. The increase in DFT was unrelated to any of the analyzed variables. We conclude that the presence of an extrapericardial patch does not prevent the increase in DFT reported with nonthoracotomy lead systems. This increase is unpredictable and occurs in almost 25% of patients.

Aged↗

Effects of waveform and polarity on defibrillation thresholds in humans using a transvenous lead system.

Minimizing defibrillation thresholds is important to allow for implantation of downsized pulse generators with reduced outputs while maintaining an adequate defibrillation safety margin. Recent studies have demonstrated a significant reduction in monophasic defibrillation thresholds with a transvenous lead when the polarity was reversed (proximal coil = cathode). However, conflicting data exist concerning the effect of polarity reversal on biphasic defibrillation thresholds. The present study was designed to evaluate prospectively the effect of waveform shape and polarity on defibrillation thresholds in humans. The group studied consisted of 26 patients undergoing cardioverter-defibrillator implantation for standard indications. All data were obtained with a transvenous lead alone configuration. Defibrillation thresholds were determined using a step-down protocol with the initial waveform and polarity randomized. Reversing polarity significantly decreased the delivered energy at defibrillation threshold with monophasic waveforms (14.8 +/- 7.1 vs 20.4 +/- 8.9 J; p < 0.001), but had no effect on the overall efficacy of biphasic waveforms (11.1 +/- 5.5 vs 12.2 +/- 6.5 J). In the subgroup of patients with high biphasic defibrillation thresholds (> or = 15 J), reversing polarity decreased the defibrillation threshold from 18.2 +/- 5.1 to 13.3 +/- 5.8 J (p < 0.001). Similarly, the improvement in defibrillation thresholds with reversing polarity of monophasic waveforms was confined to the subgroup of patients with higher defibrillation thresholds. Therefore, the lack of group effect of polarity on biphasic defibrillation thresholds may be simply due to the overall lowering of defibrillation thresholds by this waveform.

Adult↗

Electrophysiologic effects and predictors of success of combination therapy with class Ia and Ib antiarrhythmic drugs for sustained ventricular arrhythmias.

Antiarrhythmic drugs remain the first line of therapy in patients with sustained ventricular arrhythmias. Although success with class Ia antiarrhythmic medications has been limited, there is evidence that the addition of a class Ib agent may improve results. A total of 110 consecutive patients referred for electrophysiologic evaluation who had inducible sustained ventricular arrhythmias resistant to a class Ia agent underwent repeat electrophysiologic study after the addition of a class Ib drug. Patients with ejection fraction >40% and ventricular fibrillation inducible in the baseline study had an 80% response rate, whereas those with inducible ventricular tachycardia and ejection fraction < or = 40% responded 11% of the time. Responders demonstrated marked prolongation of ventricular refractoriness and slight shortening of the QRS, whereas nonresponders had QRS prolongation and a more modest increase in ventricular refractoriness. Thus, the efficacy of class Ia/Ib combination therapy in patients with inducible sustained ventricular arrhythmias refractory to a class Ia drugs alone can be predicted by baseline variables. Marked prolongation of ventricular refractoriness in the absence of QRS prolongation appears to be a key factor in the success of this combination.

Aged↗

Transvenous defibrillation lead systems.

The use of the implantable cardioverter defibrillator has grown dramatically over the past 10 years. One of the major advances in defibrillation technology is the development of transvenous lead systems. Compared with traditional epicardial lead systems, transvenous defibrillation leads reduce perioperative mortality, hospitalization, and costs. Transvenous lead systems provide reliable sensing of ventricular tachyarrhythmias, although redetection of ventricular fibrillation can be prolonged, especially with integrated lead systems. Both ramp and burst adaptive pacing are equally effective for the termination of ventricular tachycardia and are successful in up to 90% of spontaneous events. Defibrillation thresholds are higher with transvenous leads than with epicardial patches. These thresholds are reduced with the use of multiple transvenous leads, subcutaneous patches, or with reversing shock polarity. However, the development of biphasic waveforms has made the largest impact on the efficacy of these lead systems, allowing dual coil transvenous systems to be effective in about 90% of patients. Defibrillation efficacy is further enhanced and implantation simplified by the incorporation of an active pulse generator located in the left pectoral region. Active pectoral pulse generators with biphasic waveforms will be the primary lead system for new implants.

Defibrillators, Implantable↗

Acute electrophysiologic effects of amiodarone in patients with congestive heart failure.

Patients with severe congestive heart failure (CHF) are at increased risk for atrial and ventricular arrhythmias and sudden cardiac death. Amiodarone is generally well tolerated by this population and has a low proarrhythmic potential. Because of its peculiar kinetics, amiodarone requires a prolonged loading period, necessitating lengthy hospitalizations in a monitored setting. This study was planned prospectively to assess the electrophysiologic effects of an abbreviated high-dose oral load of amiodarone in patients with severe CHF and known or suspected life-threatening ventricular arrhythmias. Fifteen patients with stable CHF and known or suspected life-threatening ventricular arrhythmias underwent baseline electrophysiologic study. The study was repeated after administration of oral amiodarone, 50 mg/kg/day for 2 days in 8 divided doses (mean dose 6.9 +/- 0.4 g). After amiodarone administration, there was prolongation in virtually all conduction times and refractory periods. The prolongation of refractoriness was most pronounced in the atrium. Ventricular effective refractory periods demonstrated reverse frequency dependence. We conclude that a brief high-dose oral load of amiodarone is well tolerated by patients with CHF. It has marked and diffuse electrophysiologic actions suggestive of class I and III effects in addition to antiadrenergic and calcium blocking action. These effects are especially pronounced in the atrium.

Administration, Oral↗

Spurious discharges due to late insulation break in endocardial sensing leads for cardioverter defibrillators.

Despite their similarity to permanent pacemaker leads, endocardial sensing leads for cardioverter defibrillators have a relatively high failure rate. We describe four patients with endocardial rate sensing leads who developed inappropriate discharges 10-30 months after implantation due to small breaks in the lead insulation. This problem may become increasingly common as the number of cardioverter defibrillator implants with transvenous leads continues to grow and should be considered in the differential diagnosis of late sensing failure or inappropriate device discharges.

Aged↗

Overdrive pacing for atrial flutter.

To determine the incidence and predictors of conversion to normal sinus rhythm, a total of 124 procedures using a standard pacing protocol were performed in 101 consecutive inpatients referred for pace termination of atrial flutter. Normal sinus rhythm was achieved in 75 pace termination procedures (60%), including 10 in which atrial fibrillation occurred initially and later converted spontaneously. Sustained atrial fibrillation was provoked in 39 procedures, and atrial flutter persisted in 10. Clinical and laboratory parameters, including use of antiarrhythmic drugs, were not helpful in predicting the outcome of pacing. Of 17 patients undergoing repeat pacing for recurrent flutter, concordant results were obtained in only 4. It is concluded that: (1) overdrive pacing is only a moderately effective means of restoring sinus rhythm in patients with atrial flutter, although some change in rhythm occurs in the vast majority; (2) pacing-induced atrial fibrillation may be unstable and spontaneously converts to sinus rhythm in > 20% of cases; (3) there are no clinically useful predictors of success; (4) antiarrhythmic drugs do not facilitate pacing-induced conversion to sinus rhythm; and (5) failure to convert to sinus rhythm with 1 episode of flutter does not preclude success on subsequent occasions.

Aged↗

High dose oral amiodarone loading exerts important hemodynamic actions in patients with congestive heart failure.

OBJECTIVES: The purpose of this study was to use invasive monitoring to analyze the hemodynamic effects of both a large single dose and a 48-h loading regimen of amiodarone in patients with severe heart failure. BACKGROUND: Amiodarone is frequently used as an antiarrhythmic agent in patients with congestive heart failure, but the impact of this agent on cardiac function remains controversial. Recent successful experience with a rapid oral load of amiodarone makes invasive testing of the hemodynamic effects of oral amiodarone in such patients now feasible. METHODS: After baseline hemodynamic assessment (using balloon-tipped pulmonary artery catheters) and electrocardiographic measurements, 16 patients received 12.5 mg/kg body weight of amiodarone orally. Hemodynamic measurements were obtained hourly for 4 h. Patients then received this dose an additional seven times over the next 2 days. Hemodynamic variables and QRS, QT and PR intervals were measured after 48 h of treatment. RESULTS: Vasodilation was seen between 1 and 3 h after drug administration. Systemic vascular resistance decreased 326 +/- 135 dynes.s.cm-5, cardiac index increased 0.24 +/- 0.08 liters/min per m2 and mean arterial pressure decreased 6 +/- 3 mm Hg (mean +/- SEM, all p < 0.05). After 48 h of amiodarone administration, heart rate decreased 23 +/- 3 beats/min (p < 0.005), stroke volume increased 9 +/- 3 ml (p < 0.005), cardiac index decreased 0.23 +/- 0.09 ml/min per m2 (p < 0.05), pulmonary capillary wedge pressure increased 4 +/- 1 mm Hg (p < 0.01), right atrial pressure increased 3 +/- 1 mm Hg (p < 0.005) and QT and PR intervals were markedly prolonged (p < 0.01). CONCLUSIONS: Although the first dose caused vasodilation, a complete loading regimen of amiodarone produced a decreased heart rate with elevated filling pressures and decreased cardiac index.

Administration, Oral↗

L- and T-type Ca2+ channels in canine cardiac Purkinje cells. Single-channel demonstration of L-type Ca2+ window current.

Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-type Ca2+ "window" current. We used the on-cell, patch-clamp technique to study Ca2+ channels from isolated cardiac Purkinje cells. Patches contained one or more Ca2+ channels 75% of the time. L-type channels were seen in 69% and T-type channels in 73% of these patches. With 110 mM Ba2+ as the charge carrier, the conductances of the L- and T-type Ca2+ channels were 24.2 +/- 0.8 pS (n = 9) and 9.0 +/- 0.5 pS (n = 8), respectively (mean +/- SEM). With 110 mM Ca2+ as the charge carrier, the conductance of the L-type Ca2+ channel decreased to 9.7 +/- 1.2 pS (n = 4), whereas the T-type Ca2+ channel conductance was unchanged. Voltage-dependent inactivation was shown for both L- and T-type Ca2+ channels, although for L-type Ca2+ channel with Ba2+ as the charge carrier, inactivation took at least 30 seconds at a potential of +40 mV. After channel inactivation was complete, L-type Ca2+ channel reopenings were observed following repolarizing steps into the window voltage range. Thus, our data identify both L- and T-type Ca2+ channels in cardiac Purkinje cells and demonstrate, at the single-channel level, L-type channel transitions expected for a window current. Window current may play an important role in shaping the action potential and in arrhythmogenesis.

Animals↗

Voltage-gated chloride currents in cultured canine tracheal epithelial cells.

Chloride ions (Cl-) are concentrated in airway epithelial cells and subsequently secreted into the tracheal lumen by downhill flux through apical Cl- channels. We have studied Cl- currents in cultured canine tracheal cells using the whole-cell voltage-clamp technique. Ultrastructural techniques demonstrated that the cells used in the electrophysiological experiments possessed apical membrane specializations known to be present in the intact, transporting cell type. Cultured cells 2-6 days old were characterized by an input resistance of 3.4 +/- 0.8 G omega (n = 11) and a capacitance of 63.8 +/- 10.8 pF (n = 26). A comparison of 3 and 4 day-old cells with 5 and 6 day-old cells showed that the input resistance decreased almost 50%, and the cell capacitance and the inward and outward currents increased concomitantly approximately 200%. Cultured cells 3-4 days old held at -40 mV produced currents of 196 +/- 22 pA at 50 mV and -246 +/- 27 pA at -90 mV (n = 212) with pipette and bath solutions containing primarily 140 KCl and 140 NaCl, respectively. The chloride channel blocker diphenylamine-2-carboxylate (DPC, 100 microM) suppressed whole-cell currents by 76.8% at 60 mV; however, currents were unaffected by the stilbenes SITS (1 mM) and DNDS (1-30 microM). Replacement of K+ with Cs+ in the pipette solution did not affect the outward current, the current reversal potential, or the input resistance of the cells, indicating that the current was not significantly K+ dependent when the intrapipette solution was buffered to a Ca2+ concentration of 20 nM. The Cl-/Na+ permeability ratio was estimated to be greater than 11 as calculated from reversal potential measurements in the presence of an internal to external NaCl concentration ratio of 1:2. Current equilibrium permeabilities, relative to Cl- were: I- (2.9) much greater than NO3- (1.1) greater than or equal to Br- (1.1) greater than or equal to Cl- (1.0) greater than or equal to F- (0.93) much greater than MeSO4- (0.19) greater than or equal to gluconate (0.18) greater than or equal to aspartate (0.14). Depolarizations to potentials greater than 20 mV elicited a time-dependent component in the outward current in 71% of the cells studied. Currents inactivated with a double exponential time course at the most depolarized voltages. Recovery from inactivation was fast, holding potential-dependent, and followed a double exponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗