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Stephen R Shorofsky

Publications and source records attributed to Stephen R Shorofsky.

15 recordsLinked to original sources
PubMed2003

Role of the transverse-axial tubule system in generating calcium sparks and calcium transients in rat atrial myocytes.

Cardiac atrial cells lack a regular system of transverse tubules like that in cardiac ventricular cells. Nevertheless, many atrial cells do possess an irregular internal transverse-axial tubular system (TATS). To investigate the possible role of the TATS in excitation-contraction coupling in atrial myocytes, we visualized the TATS (labelled with the fluorescent indicator, Di-8-ANEPPS) simultaneously with Ca2+ transients and/or Ca2+ sparks (fluo-4). In confocal transverse linescan images of field-stimulated cells, whole-cell Ca2+ transients had two morphologies: 'U-shaped' transients and irregular or 'W-shaped' transients with a varying number of points of origin of the Ca2+ transient. About half (54 %, n =289 cells, 13 animals) of the cells had a TATS. Cells with TATS had a larger mean diameter (13.2 +/- 2.8 microm) than cells without TATS (11.7 +/- 2.0 microm) and were more common in the left atrium (n = 206 cells; left atrium: 76 with TATS, 30 without TATS; right atrium: 42 with TATS, 58 without TATS). Simultaneous measurement of Ca2+ sparks and sarcolemmal structures showed that cells without TATS had U-shaped transients that started at the cell periphery, and cells with TATS had W-shaped transients that began simultaneously at the cell periphery and the TATS. Most (82 out of 102 from 31 cells) 'spontaneous' (non-depolarized) Ca2+ sparks occurred within 1 microm of a sarcolemmal structure (cell periphery or TATS), and 33 % occurred within 1 pixel (0.125 microm). We conclude that the presence of a sarcolemmal membrane either at the cell periphery or in the TATS in close apposition to the sarcoplasmic reticulum is required for the initiation of an evoked Ca2+ transient and for spontaneous Ca2+ sparks.

Animals↗
PubMed2003

An antisense oligonucleotide against H1 inhibits the classical sodium current but not ICa(TTX) in rat ventricular cells.

ICa(TTX) is a sodium current component, functionally distinct from the main body of sodium current, seen in cardiac and other cells. To determine if ICa(TTX) channels are a separate isoform from the classical cardiac sodium channels, we exposed rat ventricular cells in primary culture to an antisense oligonucleotide (AON) directed against rH1 (rNav1.5): 5'-CTCCTCATACCCTCT-3'. The homologous human sequence has been identified (and confirmed by us on HEK 293 cells) as effective against hH1 expressed heterologously. Scrambled sequence (5'-CCCCCCTTATCTACT-3') controls were also included. The AON (10 microM; day 2 of exposure) reduced the classical sodium current by 69.6 % compared to untreated and 60.8 % compared to scrambled sequence (10 microM; day 2 of exposure) controls (mean +/- S.E.M. maximum peak inward current density of -8.23 +/- 0.60 pA pF-1, 18 cells, for untreated; -6.37 +/- 0.79 pA pF-1, 16 cells, for scrambled sequence; and -2.50 +/- 0.31 pA pF-1, 18 cells, for AON-treated cells). The two control groups are not significantly different from each other, but are both significantly different from the AON-treated group (P < 0.001). The inhibition was specific for sodium channels, with no significant AON effect on the L-type calcium current. This confirms that H1 generates the classical cardiac sodium current. This same AON at the same concentration and time of exposure had no significant effect on ICa(TTX) (mean of -4.72 +/- 0.55, 15 cells; -5.47 +/- 0.53, 13 cells; and -5.04 +/- 0.63 pA pF-1, 15 cells, for untreated controls, scrambled controls and AON treated, respectively). Hence, ICa(TTX), which is functionally distinct from the classical cardiac sodium current, is encoded by a distinct gene.

Animals↗
PubMed2003

Effect of shock polarity on defibrillation thresholds with a hybrid patch-coil lead system.

INTRODUCTION: Understanding the factors that affect defibrillation thresholds (DFTs) has important implications both for optimization of defibrillation efficacy and for the design of new lead systems. The objective of this prospective study was to evaluate the effect of shock polarity on defibrillation efficacy at the time of routine pulse generator replacement in patients with a hybrid patch-coil lead system. METHODS: Each patient underwent 4 assessments of DFT: monophasic or biphasic shock with standard or reversed polarity, with the order of testing with respect to polarity randomized. In standard polarity, the right atrial coil is the anode and the left ventricular patch is the cathode. RESULTS: The study population of 30 patients was 80% men with a mean age of 65 +/- 9 years and a mean left ventricular ejection fraction of 33 +/- 12%. There was a significant 21% decrease in the mean monophasic DFT with reversed polarity shocks (13.1 +/- 5.9 J vs. 16.6 +/- 6.5 J, p < 0.01). Reversal of shock polarity did not have a significant effect on the mean biphasic DFT (8.0 +/- 4.8 J vs. 8.5 +/- 4.3 J for reversed and standard polarity respectively, p = NS). However, when an elevated biphasic DFT (>or=15 J) was present in either standard or reversed polarity, a significant decrease in DFT was observed when the opposite polarity was used (16.7 +/- 2.5 J vs. 9.1 +/- 2.7 J, n = 9, p < 0.0001). CONCLUSION: Reversal of shock polarity markedly improves monophasic DFTs with the patch-coil lead configuration. The DFT should be determined with both shock polarities to optimize defibrillation efficacy for patients with high biphasic DFTs (>or=15 J).

Aged↗
PubMed2003

Safety of a single successful conversion of ventricular fibrillation before the implantation of cardioverter defibrillators.

UNLABELLED: Multiple successful conversions of ventricular fibrillation (VF) at 10 J below the maximum output of implantable cardioverter defibrillator (ICD) have been recommended as a minimum device implantation criterion. This recommendation is based on the probabilistic properties of defibrillation that necessitates multiple shocks to establish an adequate safety margin for the conversion of subsequent spontaneous arrhythmias. We hypothesized that a single successful shock at a 14 J may suffice. METHODS AND RESULTS: The Low Energy Safety Study (LESS) enrolled 720 patients undergoing initial ICD implantation with a dual-coil transvenous lead and active pulse generator. At implant, an enhanced defibrillation threshold (DFT++) was determined by a rigorous protocol beginning at 14 J, and requiring at least 4 shocks. Fifty percent of all patients were then randomized to full output shock energy and the conversion rates for spontaneous ventricular tachyarrhythmias at rates > 200 beats/min were measured. There were 318 patients randomized to 31 J, of whom 254 were successfully defibrillated by an initial 14 J shock. During a mean follow-up of 24 +/- 12 months, 112 spontaneous VF episodes occurred in 31 patients. The combined conversion success of the first and second shock (when needed) did not differ between the subgroup of patients who were successfully defibrillated by an initial 14 J shock, regardless of the results of additional testing, and the whole cohort who underwent more systematic testing (97% vs 97%). All spontaneous episodes of VF were successfully treated during long-term follow-up. CONCLUSIONS: A first successful shock of 14 J may be a sufficient endpoint to allow the implantation of ICDs with the Triad lead configuration, when programming all shocks to 31 J.

Aged↗
PubMed2003

Distal right ventricular coil position reduces defibrillation thresholds.

UNLABELLED: Distal RV Coil Position Reduces DFTs. INTRODUCTION: Understanding the factors that affect defibrillation thresholds (DFTs) has important implications both for optimization of defibrillation efficacy and for the design of new transvenous leads. The aim of this prospective study was to test the hypothesis that defibrillation efficacy is improved with the right ventricular (RV) coil in a distal position compared with a more proximal RV coil position. METHODS AND RESULTS: A novel defibrillation lead with three adjacent RV defibrillation coils (distal 0.8 cm, middle 3.7 cm, proximal 0.8 cm) was used for this study to permit comparison of DFTs with the proximal and distal RV coil positions without lead repositioning. In the distal RV configuration, the distal and middle RV coils were connected electrically as the anode for defibrillation. In the proximal RV configuration, the middle and proximal coils were the anode. A superior vena cava (SVC) coil and active can were connected electrically as the cathode (reversed polarity, RV-->Can+SVC). In each patient, the DFT was measured twice using a binary search protocol with the distal RV and proximal RV configurations, with the order of testing randomized. The study cohort consisted of 31 subjects (mean age 65 +/- 12 years, mean left ventricular ejection fraction 30% +/- 16%, 81% male predominance). The mean delivered energy (8.2 +/- 5.3 J vs 11.2 +/- 6.1 J), leading-edge voltage (335 +/- 109 V vs 393 +/- 118 V), and peak current (11.6 +/- 5.2 A vs 14.9 +/- 7.3 A) at DFT all were significantly lower with the distal RV configuration compared to the proximal RV configuration (P < 0.01 for all comparisons). CONCLUSION: DFTs are significantly reduced with the distal RV configuration compared to the proximal RV configuration. Defibrillation leads should be designed with the shortest tip to coil distance that can be achieved without compromising ventricular fibrillation sensing.

Aged↗
PubMed2002

Effects of selective autonomic blockade on T-wave alternans in humans.

BACKGROUND: T-wave alternans (TWA) is an important noninvasive measure of ventricular arrhythmia vulnerability. This study tested the hypothesis that the autonomic nervous system influences TWA measurement in high-risk subjects with coronary artery disease. METHODS AND RESULTS: T-wave alternans was measured in 60 patients with coronary artery disease, left ventricular dysfunction, and inducible sustained ventricular tachycardia during electrophysiological studies. All patients had TWA measured at baseline with atrial pacing at 100 bpm (600 ms), 109 bpm (550 ms), and 120 bpm (500 ms). After a 10-minute recovery period, TWA was measured again after sympathetic blockade (esmolol, n=20), parasympathetic blockade (atropine, n=20), or no intervention (control subjects, n=20). The prevalence of significant TWA was unchanged compared with baseline after atropine infusion and in the control group. In contrast, the amplitude of TWA in the vector magnitude lead was significantly reduced after esmolol infusion (P<0.001), and the number of positive TWA tests was reduced by 50% (70% versus 35%, P<0.05). CONCLUSIONS: Our findings have important implications for the use of TWA to risk-stratify patients for life-threatening ventricular arrhythmias and provide a new potential mechanism for the reduction in sudden cardiac death conferred by beta-blockers among patients with coronary artery disease and congestive heart failure.

Adrenergic beta-Antagonists↗
PubMed2002

Clinical predictors of defibrillation thresholds with an active pectoral pulse generator lead system.

Active pectoral pulse generators are used routinely for initial ICD placement because they reduce DFTs and simplify the implantation procedure. Despite the common use of these systems, little is known regarding the clinical predictors of defibrillation efficacy with active pulse generator lead configurations. Such predictors would be helpful to identify patients likely to require higher output devices or more complicated implantations. This was a prospective evaluation of DFT using a uniform testing protocol in 102 consecutive patients with an active pectoral can and dual coil transvenous lead. For each patient, the DFT was measured with a step-down protocol. In addition, 34 parameters were assessed including standard clinical echocardiographic and radiographic measures. Multivariate stepwise regression analysis was performed to identify independent predictors of the DFT. The mean DFT was 9.3 +/- 4.6 J and 93% (95/102) of patients had a DFT < or = 15 J. The QRS duration, interventricular septum thickness, left ventricular mass, and mass index were significant but weak (R < 0.3) univariate predictors of DFT. The left ventricular mass was the only independent predictor by multivariate analysis, but this parameter accounted for < 5% of the variability of DFT measured (adjusted R2 = 0.047, P = 0.017). The authors concluded that an acceptable DFT (< 15 J) is observed in > 90% of patients with this dual coil and active pectoral can lead system. Clinical factors are of limited use for predicting DFTs and identifying those patients who will have high thresholds.

Aged↗
PubMed2002

Lack of benefit of an active pectoral pulse generator on atrial defibrillation thresholds.

INTRODUCTION: Atrial defibrillation can be achieved with standard implantable cardioverter defibrillator leads, which has led to the development of combined atrial and ventricular devices. For ventricular defibrillation, use of an active pectoral electrode (active can) in the shocking pathway markedly reduces defibrillation thresholds (DFTs). However, the effect of an active pectoral can on atrial defibrillation is unknown. METHODS AND RESULTS: This study was a prospective, randomized, paired comparison of two shock configurations on atrial DFTs in 33 patients. The lead system evaluated was a dual-coil transvenous defibrillation lead with a left pectoral pulse generator emulator. Shocks were delivered either between the right ventricular coil and proximal atrial coil (lead) or between the right ventricular coil and an active can in common with the atrial coil (active can). Delivered energy at DFT was 4.2 +/- 4.1 J in the lead configuration and 5.0 +/- 3.7 J in the active can configuration (P = NS). Peak current was 32% higher with an active can (P < 0.01), whereas shock impedance was 18% lower (P < 0.001). Moreover, a low threshold (< or = 3 J) was observed in 61% of subjects in the lead configuration but in only 36% in the active can configuration (P < 0.05). There were no clinical predictors of the atrial DFT. CONCLUSION: These results indicate that low atrial DFTs can be achieved using a transvenous ventricular defibrillation lead. Because no benefit was observed with the use of an active pectoral electrode for atrial defibrillation, programmable shock vectors may be useful for dual-chamber implantable cardioverter defibrillators.

Atrial Fibrillation↗
PubMed2002

Influence of QRS duration on the prognostic value of T wave alternans.

INTRODUCTION: T wave alternans (TWA) is a promising new noninvasive marker of arrhythmia vulnerability that quantifies beat-to-beat changes in ventricular repolarization. Secondary repolarization abnormalities are common in subjects with wide QRS complexes. However, the relationship between TWA and QRS prolongation has not been evaluated. The goal of this study was to determine if QRS prolongation influences the prevalence or prognostic value of TWA. METHODS AND RESULTS: The study consisted of 108 consecutive patients with coronary artery disease and left ventricular ejection fraction < or = 40% who were referred for electrophysiologic studies. Patients underwent TWA testing using bicycle ergometry in the absence of beta-blockers or antiarrhythmic drugs. The primary endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator therapy. The prognostic value of TWA was assessed in the entire cohort and in two subgroups: QRS < 120 msec (normal, n = 62) and QRS > or = 120 msec (prolonged, n = 46). TWA (hazard ratio 2.2, P = 0.03) and QRS prolongation (hazard ratio 2.2, P = 0.01) were both significant and independent predictors of arrhythmic events. QRS prolongation had no effect on the prevalence of positive TWA tests (QRS < 120 msec: 48%, QRS > or = 120 msec: 50%, P = NS). TWA was a highly significant predictor of events in patients with a normal QRS (hazard ratio 5.8, P = 0.02). In contrast, TWA was not useful for risk stratification in subjects with QRS prolongation (hazard ratio 1.1, P = 0.8). CONCLUSION: TWA is useful only for risk stratification in the absence of QRS prolongation. The presence of QRS prolongation and left ventricular ejection fraction < or = 40% may be sufficient evidence of an adverse prognosis that additional risk stratification is not useful or necessary.

Adult↗
PubMed2002

Exercise is superior to pacing for T wave alternans measurement in subjects with chronic coronary artery disease and left ventricular dysfunction.

INTRODUCTION: T wave alternans (TWA) is a heart rate-dependent marker of vulnerability to ventricular arrhythmias. Atrial pacing and exercise both are used as provocative stimuli to elicit TWA. However, the prognostic value of the two testing methods has not been compared. The aim of this prospective study was to compare the prognostic value of TWA measured during bicycle exercise and atrial pacing in a large cohort of high-risk patients with ischemic heart disease and left ventricular dysfunction. METHODS AND RESULTS: This was a prospective study of 251 patients with coronary artery disease and left ventricular dysfunction who were referred for electrophysiologic studies (EPS) for standard clinical indications. Patients underwent TWA testing using bicycle ergometry (exercise TWA, n = 144) and/or atrial pacing (pacing TWA, n = 178). The primary endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator therapy. The predictive value of exercise and pacing TWA for EPS results and for endpoint events was determined. Exercise and pacing TWA both were significant predictors of EPS results (odds ratios 3.0 and 2.9 respectively, P < 0.02). Kaplan-Meier survival analysis of the primary endpoint revealed that exercise TWA was a significant predictor of events (hazard ratio 2.2, P = 0.03). In contrast, pacing TWA had no prognostic value for endpoint events (hazard ratio 1.1, P = 0.8). CONCLUSION: TWA should be measured during exercise when it is used for clinical risk stratification. EPS results may not be an adequate surrogate for spontaneous events when evaluating new risk stratification tests.

Aged↗
PubMed2002

Advanced rhythm discrimination for implantable cardioverter defibrillators using electrogram vector timing and correlation.

INTRODUCTION: Discrimination of ventricular and supraventricular arrhythmias remains one of the major challenges for appropriate implantable defibrillator (ICD) therapy delivery. The electrogram vector timing and correlation (VTC) algorithm was developed for such rhythm discrimination. The VTC algorithm differentiates normally conducted supraventricular beats from abnormally conducted ventricular beats by comparing the timing and correlation of rate and shock channel electrograms. METHODS AND RESULTS: Rate and shock channel electrograms of sinus rhythm and induced arrhythmias were collected from 93 patients during ICD placement. The algorithm was developed using data from 50 patients and prospectively tested in a software model with the remaining 43 patients. A sinus rhythm reference was formed by averaging complexes of the shock channel signal aligned by the peak amplitude of the rate channel. Eight features measuring the amplitude and timing of shock channel signal characteristics were extracted from the reference for comparison. When a high-rate rhythm was detected, the VTC algorithm computed the correlation of the arrhythmia complex features with the reference. Rhythms with a sufficient number of uncorrelated beats were classified as ventricular tachycardia (VT). In a dual-chamber implementation, the VTC algorithm is integrated with ventricular and atrial rate comparison (V>A) and stability above an atrial fibrillation rate threshold. The test set consisted of 117 arrhythmias. Dual-chamber sensitivity was 100% (81/81 VT) and specificity was 97% (35/36 supraventricular tachycardia). Single-chamber analysis demonstrated 99% sensitivity and 97% specificity. CONCLUSION: The VTC algorithm demonstrated high sensitivity and specificity in discriminating between ventricular and supraventricular arrhythmias.

Aged↗
PubMed2002

Cardiovascular responses to repetitive defibrillation during implantable cardioverter-defibrillator testing.

OBJECTIVE: To study the effects of electrical applications and subsequent postshock hypotension on myocardial performance and vascular tone during implantable cardioverter-defibrillator (ICD) placement. DESIGN: Prospective, blinded, observational investigation. SETTING: Single, university-affiliated institution. PARTICIPANTS: Twenty patients undergoing elective ICD placement and testing under general anesthesia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial measurements were made of hemodynamic variables, left ventricular end-systolic (ESA) and end-diastolic (EDA) areas, fractional-area-of-contraction (FAC), time of hypoperfusion (when mean arterial pressure < or =50 mmHg postshock), and applied conversion energy. Multiple linear regression was performed to determine correlations among collected variables, and repeated measures analysis of variance was used to compare mean values. Minimal changes were detected in mean values of arterial, pulmonary, and central venous pressures; cardiac output; heart rate; and mixed venous saturation during repeated testing. Percentage changes in cardiac index (CI) rose and systemic vascular resistance index (SVRI) fell, however, as the number of shocks increased, reaching significance at the seventh and eighth shocks (v baseline; both p = 0.015). The percentage change in CI was linearly related to hypoperfusion time and accumulated energy (%deltaCI = 1.553 + [0.068 x sigma hypoperfusion time [sec]], r = 0.92, p < 0.001; %deltaCI = 0.326 + [0.125 x sigma Energy [J]], r = 0.94, p < 0.001). The percentage change in SVRI was inversely related to hypoperfusion time and accumulated energy (%deltaSVRI = 2.195 - [0.122 x sigma energy [J]], r = 0.79, p = 0.004; %deltaSVRI = 0.542 - [0.0634 - sigma hypoperfusion time [sec]], r = 0.73, p = 0.01). Echocardiographic EDA, ESA, and FAC were not significantly changed but showed substantial variability. CONCLUSION: Hemodynamic stability was generally well maintained during ICD placement and testing. Increases in CI were associated with concurrent reductions in systemic afterload, rather than enhanced FAC. Increasing postshock hypotension and applied energy were associated with decreases in CI and systemic afterload. Insignificant, but highly variable, changes were noted echocardiographically.

Adult↗
PubMed2002

Effect of shock polarity on the efficacy of transthoracic atrial defibrillation.

BACKGROUND: The energy requirement for internal ventricular defibrillation is reduced by reversal of shock polarity. The influence of shock polarity on the efficacy of transthoracic atrial defibrillation is unknown. METHODS: This prospective, randomized study enrolled 110 consecutive patients who were referred for elective cardioversion of persistent atrial fibrillation (AF). The electrodes were placed in the anteroposterior position. The patients were randomized to receive either standard (anterior pad = cathode) or reversed polarity (anterior pad = anode) shocks with a damped sinusoidal monophasic waveform. A step-up protocol was used to estimate the cardioversion threshold. The initial shock energy was 50 J, with subsequent increments to 100, 200, 300, and 360 J in the event of cardioversion failure. RESULTS: Sixty-four percent of the patient population were men, with a mean age of 66 +/- 13 years and a mean duration of AF of 242 +/- 556 days. The overall success rates of cardioversion were 84% for standard polarity and 78% for reversed polarity (P not significant). Among the patients who were successfully cardioverted, the mean atrial defibrillation threshold was 198 +/- 103 J for standard polarity and 212 +/- 107 J for reversed polarity (P not significant). CONCLUSIONS: Reversal of shock polarity does not improve transthoracic cardioversion efficacy with a standard damped sinusoidal monophasic waveform. Alternate strategies should be considered for patients who fail external cardioversion, such as adjunctive pharmacologic treatment, use of a biphasic shock waveform, or internal cardioversion.

Aged↗