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Biomedical subjects

Stephen R Shorofsky

Publications and source records attributed to Stephen R Shorofsky.

At least 19 recordsLinked to original sources
PubMed2006

Cellular and molecular determinants of altered Ca2+ handling in the failing rabbit heart: primary defects in SR Ca2+ uptake and release mechanisms.

Myocytes from the failing myocardium exhibit depressed and prolonged intracellular Ca(2+) concentration ([Ca(2+)](i)) transients that are, in part, responsible for contractile dysfunction and unstable repolarization. To better understand the molecular basis of the aberrant Ca(2+) handling in heart failure (HF), we studied the rabbit pacing tachycardia HF model. Induction of HF was associated with action potential (AP) duration prolongation that was especially pronounced at low stimulation frequencies. L-type calcium channel current (I(Ca,L)) density (-0.964 +/- 0.172 vs. -0.745 +/- 0.128 pA/pF at +10 mV) and Na(+)/Ca(2+) exchanger (NCX) currents (2.1 +/- 0.8 vs. 2.3 +/- 0.8 pA/pF at +30 mV) were not different in myocytes from control and failing hearts. The amplitude of peak [Ca(2+)](i) was depressed (at +10 mV, 0.72 +/- 0.07 and 0.56 +/- 0.04 microM in normal and failing hearts, respectively; P < 0.05), with slowed rates of decay and reduced Ca(2+) spark amplitudes (P < 0.0001) in myocytes isolated from failing vs. control hearts. Inhibition of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a revealed a greater reliance on NCX to remove cytosolic Ca(2+) in myocytes isolated from failing vs. control hearts (P < 0.05). mRNA levels of the alpha(1C)-subunit, ryanodine receptor (RyR), and NCX were unchanged from controls, while SERCA2a and phospholamban (PLB) were significantly downregulated in failing vs. control hearts (P < 0.05). alpha(1C) protein levels were unchanged, RyR, SERCA2a, and PLB were significantly downregulated (P < 0.05), while NCX protein was significantly upregulated (P < 0.05). These results support a prominent role for the sarcoplasmic reticulum (SR) in the pathogenesis of HF, in which abnormal SR Ca(2+) uptake and release synergistically contribute to the depressed [Ca(2+)](i) and the altered AP profile phenotype.

Abdomen↗
PubMed2006

Coronary sinus electrode does not reduce atrial defibrillation thresholds.

BACKGROUND: Atrial defibrillation can be achieved with a conventional dual-coil, active pectoral implantable cardioverter-defibrillator (ICD) lead system. Shocking vectors that incorporate an additional electrode in the CS have been used, but it is unclear if they improve atrial DFTs. OBJECTIVE: The objective of this prospective, randomized study was to determine if a coronary sinus (CS) electrode reduces atrial defibrillation thresholds (DFTs). METHODS: This was a prospective study of 36 patients undergoing initial ICD implant for standard indications. A defibrillation lead with superior vena cava (SVC) and right ventricular (RV) shocking coils was implanted in the RV. An active can emulator (Can) was placed in a pre-pectoral pocket. A lead with a 4 cm long shocking coil was placed in the CS. Atrial DFTs were determined in the following 3 shocking configurations in each patient, with the order of testing randomized: RV --> SVC + Can (Ventricular Triad), distal CS --> SVC + Can (Distal Atrial Triad), and proximal CS --> SVC + Can (Proximal Atrial Triad). RESULTS: The Proximal and Distal Atrial Triad configurations were both associated with significant reductions in peak current (p < 0.01), but this effect was offset by significant increases in shock impedance (p < 0.01), resulting in no net change in the peak voltage or DFT energy in comparison to the Ventricular Triad configuration (Ventricular Triad: 4.9 +/- 6.6 J, Proximal Atrial Triad: 3.3 +/- 4.1J, Distal Atrial Triad: 4.4 +/- 6.7 J, p > 0.2). CONCLUSION: Shocking vectors that incorporate a CS coil do not significantly improve atrial defibrillation efficacy. Since the Ventricular Triad shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.

Atrial Fibrillation↗
PubMed2006

Management of arrhythmias in the emergency department.

The authors present practical and concise advice on initial diagnosis and management of arrhythmias, on arrhythmia devices, and on syncope. There is discussion of tachyarrhythmias, both wide and narrow, bradyarrhythmias, and management of pacemakers and defibrillators. Common pitfalls and concerns are addressed.

Anti-Arrhythmia Agents↗
PubMed2006

Effect of an active abdominal pulse generator on defibrillation thresholds with a dual-coil, transvenous ICD lead system.

INTRODUCTION: Many patients with implantable cardioverter defibrillators (ICDs) have older lead systems, which are usually not replaced at the time of pulse generator replacement unless a malfunction is noted. Therefore, optimization of defibrillation with these lead systems is clinically important. The objective of this prospective study was to determine if an active abdominal pulse generator (Can) affects chronic defibrillation thresholds (DFTs) with a dual-coil, transvenous ICD lead system. METHODS AND RESULTS: The study population consisted of 39 patients who presented for routine abdominal pulse generator replacement. Each patient underwent two assessments of DFT using a step-down protocol, with the order of testing randomized. The distal right ventricular (RV) coil was the anode for the first phase of the biphasic shocks. The proximal superior vena cava (SVC) coil was the cathode for the Lead Alone configuration (RV --> SVC). For the Active Can configuration, the SVC coil and Can were connected electrically as the cathode (RV --> SVC + Can). The Active Can configuration was associated with a significant decrease in shock impedance (39.5 +/- 5.8 Omega vs. 50.0 +/- 7.6 Omega, P < 0.01) and a significant increase in peak current (8.3 +/- 2.6 A vs. 7.2 +/- 2.4 A, P < 0.01). There was no significant difference in DFT energy (9.0 +/- 4.6 J vs. 9.8 +/- 5.2 J) or leading edge voltage (319 +/- 86 V vs. 315 +/- 83 V). An adequate safety margin for defibrillation (> or =10 J) was present in all patients with both shocking configurations. CONCLUSION: DFTs are similar with the Active Can and Lead Alone configurations when a dual-coil, transvenous lead is used with a left abdominal pulse generator. Since most commercially available ICDs are only available with an active can, our data support the use of an active can device with this lead system for patients who present for routine pulse generator replacement.

Abdominal Muscles↗
PubMed2005

Repositioning of a dislodged and fibrosed ventricular lead.

UNLABELLED: This is a case of a 61 year old African American female with history of end stage renal disease on hemodialysis. She had a dual chamber permanent pacemaker implanted in 2003 for symptomatic bradycardia. Over the past several months the patient had problems with access for dialysis. The right arm AV fistula was occluded. The patient had multiple temporary central catheter placed for dialysis over the past 3 months. The patient was admitted for superior vena-cava syndrome. CT scan of the thorax and neck showed occluded right and left subclavian system. An incidental finding was the right ventricular (RV) lead been dislodged and the tip being in the inferior vena cava. Surgical and non-surgical options were discussed with the patient and she chose to go the less invasive route. The patient underwent a RV lead revision. Using different stylets the RV lead was repositioned in the RV with good pacing and sensing characteristics. CONCLUSIONS: Successful repositioning of an old dislodged RV pacing lead using stylets and eliminating the need for invasive procedure like lead extraction.

Device Removal↗
PubMed2005

Clinical predictors of atrial defibrillation thresholds with a dual-coil, active pectoral lead system.

OBJECTIVES: The purpose of this study was to identify clinical predictors of atrial defibrillation thresholds (DFTs) with standard implantable cardioverter-defibrillator (ICD) leads. BACKGROUND: Atrial defibrillation can be achieved with active pectoral, dual-coil transvenous ICD lead systems. If clinical predictors of atrial defibrillation efficacy with these lead systems were identified, they could be used to predict which patients may require more complex lead systems for atrial defibrillation, such as a coronary sinus electrode. METHODS: This was a prospective study of 135 consecutive patients undergoing initial ICD implant for standard indications. The lead system evaluated was a transvenous defibrillation lead with coils in the superior vena cava (SVC) and right ventricular apex (RV), and a left pectoral pulse generator emulator (CAN). The shocking pathway was RV-->SVC+CAN. Atrial DFT was measured using a step-up protocol. Clinical and echocardiographic parameters were evaluated as predictors of atrial DFT and multiple linear regression was performed. RESULTS: Mean atrial DFT was 4.6 +/- 3.8 J. Atrial DFT was < or =3 J in 70 patients (52%) and < or = 10 J in 97% of patients. The highest atrial DFT was 20 J (one patient). Left atrial size (r = 0.21, P = .01) and left ventricular end-diastolic diameter (r = 0.19, P = .02) were independent predictors of atrial DFT. However, these two predictors accounted for only 6% of the variability in atrial DFT. CONCLUSIONS: Clinical parameters are of limited use in predicting atrial DFT with a dual-coil, active pectoral ICD lead system. Because the RV--> SVC + CAN shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.

Atrial Fibrillation↗
PubMed2005

Improved defibrillation efficacy with an ascending ramp waveform in humans.

OBJECTIVES: The purpose of this study was to compare an ascending ramp waveform (RAMP) with a standard, clinically available biphasic truncated exponential waveform (BTE) for defibrillation in humans. BACKGROUND: In animal studies, RAMP had a lower defibrillation threshold (DFT) than BTE. METHODS: We studied 63 patients at implantable cardioverter-defibrillator placement using a dual-coil lead and left pectoral active can. The subjects were divided into two groups, one with a 12-ms ascending first phase and one with a 7-ms ascending first phase. Phase 2 of RAMP for both groups was a truncated exponential decay with 65% tilt and reversed polarity. The BTE had a 50% tilt in each phase. DFT and upper limit of vulnerability (ULV) were measured for both waveforms using a binary search protocol. RESULTS: The patient population was 77% male, with a mean age of 63 +/- 10 years and ejection fraction of 33 +/- 13%. Delivered energy at DFT was lower with the 7-ms RAMP vs BTE (5.4 +/- 2.6 J vs 6.5 +/- 3.4 J; P < .01) but unchanged with the 12-ms RAMP (7.4 +/- 4.5 J vs 7.1 +/- 4.9 J). Maximal voltage at DFT was significantly lower with either RAMP compared to BTE (P < .01). There was a strong correlation between ULV and DFT for both RAMP and BTE (P < .01). CONCLUSIONS: The 7-ms ascending ramp waveform significantly reduced delivered energy (18%) and voltage (24%) at DFT, whereas the 12-ms RAMP reduced only DFT voltage. This is the first report of a waveform that is superior to a BTE for defibrillation in humans. ULV correlates with DFT for RAMP, supporting the use of ULV testing for implantation of devices.

Algorithms↗
PubMed2004

Efficacy of transthoracic cardioversion of atrial fibrillation using a biphasic, truncated exponential shock waveform at variable initial shock energies.

Biphasic shocks are more effective than damped sine wave monophasic shocks for transthoracic cardioversion (CV) of atrial fibrillation (AF), but the optimal protocol for CV with biphasic shocks has not been defined. We conducted a prospective, randomized study of 120 consecutive patients with persistent AF to delineate the dose-response curve for CV of AF with a biphasic truncated exponential shock waveform and to identify clinical predictors of shock efficacy. Our data suggest that the initial shock energy for CV with this waveform should be 200 J if the patient weighs <90 kg and 360 J if the patient weighs >/=90 kg.

Aged↗
PubMed2004

Enhanced detection of arrhythmia vulnerability using T wave alternans, left ventricular ejection fraction, and programmed ventricular stimulation: a prospective study in subjects with chronic ischemic heart disease.

INTRODUCTION: In previous studies, the prognostic value of T wave alternans (TWA) was similar to that of programmed ventricular stimulation (PVS). However, presently it is unclear if TWA and PVS identify the same patients or provide complementary risk stratification information. In addition, the effects of left ventricular ejection fraction (LVEF) on the prognostic value of TWA are unknown. The aim of this study was to determine if combined assessment of TWA, LVEF, and PVS improves arrhythmia risk stratification. METHODS AND RESULTS: This was a prospective study of 144 patients with coronary artery disease and LVEF < or =40% who were referred for PVS for standard clinical indications. The endpoint was the combined incidence of death, sustained ventricular arrhythmias, and appropriate implantable cardioverter defibrillator (ICD) therapy. TWA (hazard ratio 2.2, P = 0.03) and PVS (hazard ratio 1.9, P = 0.05) both were significant predictors of endpoint events, and TWA was the only independent predictor. LVEF markedly influenced the prognostic value of TWA, which was a potent predictor of events in subjects with LVEF between 30% and 40% (event rates: TWA+ 36%, TWA- 0%, P = 0.001) but did not predict events in subjects with LVEF <30% (hazard ratio 1.1, P > 0.5). PVS successfully identified additional low-risk patients within the cohort with negative or indeterminate TWA results (hazard ratio 4.7, P = 0.015) but did not provide incremental prognostic information for TWA+ patients (hazard ratio 0.9, P > 0.5). CONCLUSION: The combined use of TWA, LVEF, and PVS is a promising new approach to arrhythmia risk stratification that permits identification of high-risk and very-low-risk patients.

Aged↗
PubMed2004

Optimization of atrial defibrillation with a dual-coil, active pectoral lead system.

INTRODUCTION: Atrial defibrillation can be achieved with standard implantable cardioverter defibrillator (ICD) leads, but the optimal shocking configuration is unknown. The objective of this prospective study was to compare atrial defibrillation thresholds (DFTs) with three shocking configurations that are available with standard ICD leads. METHODS AND RESULTS: This study was a prospective, randomized, paired comparison of shocking configurations on atrial DFTs in 58 patients. The lead system evaluated was a transvenous defibrillation lead with coils in the superior vena cava (SVC) and right ventricular apex (RV) and a left pectoral pulse generator emulator (Can). In the first 33 patients, atrial DFT was measured with the ventricular triad (RV --> SVC + Can) and unipolar (RV --> Can) shocking pathways. In the next 25 patients, atrial DFT was measured with the ventricular triad and the proximal triad (SVC --> RV + Can) configurations. Delivered energy at DFT was significantly lower with the ventricular triad compared to the unipolar configuration (4.7 +/- 3.7 J vs 10.1 +/- 9.5 J, P < 0.001). Peak voltage and shock impedance also were significantly reduced (P < 0.001). There was no significant difference in DFT energy when the ventricular triad and proximal triad shocking configurations were compared (3.6 +/- 3.0 J vs 3.4 +/- 2.9 J for ventricular and proximal triad, respectively, P = NS). Although shock impedance was reduced by 13% with the proximal triad (P < 0.001), this effect was offset by an increased current requirement (10%). CONCLUSION: The ventricular triad is equivalent or superior to other possible shocking pathways for atrial defibrillation afforded by a dual-coil, active pectoral lead system. Because the ventricular triad is also the most efficacious shocking pathway for ventricular defibrillation, this pathway should be preferred for combined atrial and ventricular defibrillators.

Aged↗
PubMed2004

Comparison of step-down and binary search algorithms for determination of defibrillation threshold in humans.

Determination of DFT is an integral part of ICD implantation. Two commonly used methods of DFT determination, the step-down method and the binary search method, were compared in 44 patients undergoing ICD testing for standard clinical indications. The step-down protocol used an initial shock of 18 J. The binary search method began with a shock energy of 9 J and successive shock energies were increased or decreased depending on the success of the previous shock. The DFT was defined as the lowest energy that successfully terminated ventricular fibrillation. The binary search method has the advantage of requiring a predetermined number of shocks, but some have questioned its accuracy. The study found that (mean) DFT obtained by the step-down method was 8.2 +/- 5.0, whereas by the binary search method DFT was 8.1 +/- 0.7 J, P = NS. DFT differed by no more than one step between methods in 32 (71%) of patients. The number of shocks required to determine DFT by the step-down method was 4.6 +/- 1.4, whereas by definition, the binary search method always required three shocks. In conclusion, the binary search method is preferable because it is of comparable efficacy and requires fewer shocks.

Aged↗
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↗