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BACKGROUND: The hemodialysis procedure may play a role in the elevated risk of sudden cardiac death seen in hemodialysis patients. METHODS: Microvolt T wave alternans, a promising noninvasive electrophysiological test developed to measure sudden cardiac death risk, was used to test the hypotheses that high-risk hemodialysis patients commonly manifest cardiac electrophysiology that is associated with higher sudden death risk in nondialysis patients and that the hemodialysis procedure modifies cardiac electrophysiology in a manner predisposing to malignant ventricular arrhythmias. To test this hypothesis, microvolt T wave alternans tracings were done in 9 patients before and immediately after an early week hemodialysis session. RESULTS: 7 of 9 individuals had non-negative (i.e. higher risk) tracings either before or after hemodialysis. 2 of 4 subjects with tracings initially negative before hemodialysis became non-negative after hemodialysis. CONCLUSION: This pilot study provides the first objective preliminary evidence using microvolt T wave alternans that high-risk hemodialysis patients commonly exhibit abnormal cardiac repolarization and that hemodialysis treatments can acutely alter repolarization in a potentially harmful manner.

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A 70-year-old man with a single-chamber implantable cardioverter defibrillator (ICD) placed for ventricular tachycardia presented with syncope. He was found to have ventricular flutter/fibrillation with capacitor charge time in excess of 1 minute before defibrillation. The excessive charge time was secondary to ICD capacitor malfunction. The generator was explanted and replaced, and the patient recovered uneventfully.

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OBJECTIVE: To assess the out-of-hospital cardiac arrest (OHCA) survival advantage after providing police with automated external defibrillators (AEDs) in rural and suburban Indiana. METHODS: An observational evaluation was conducted in six Indiana counties (population: 464,741) before (retrospective) and after (prospective) training and equipping police with AEDs. The primary outcome evaluated was survival to hospital discharge for all cases of ventricular tachycardia/ventricular fibrillation (VT/VF) OHCA. Other factors evaluated include age, gender, race, arrest location, witnessed arrest, bystander cardiopulmonary resuscitation, response intervals, and survival to discharge for all OHCAs. Results are reported using chi-square, Student's t-test, and logistic regression. RESULTS: Police were equipped with 112 AEDs, increasing total defibrillator capability by 43.2%. During the study period, AED-equipped police responded prior to emergency medical services (EMS) in 26 of 388 cases (6.7%). The time intervals from 911 call-to-scene and 911 call-to-shock were shortened by 1.6 minutes (95% confidence interval [95% CI] = 0.0 to 3.1, p = 0.05) and 4.8 minutes (95% CI = 1.3 to 8.3, p = 0.008), respectively, with police response as compared with EMS response. Survival to hospital discharge for VT/VF OHCA was 15.0% (3/20) in cases in which police responded first and 10.0% (16/160) in cases in which EMS responded first (relative risk [RR] 0.63, 95% CI = 0.17 to 2.39, p = 0.45). Survival to hospital discharge for VT/VF OHCA did not improve from the prestudy period (16/204, 7.8%) to after police AED availability (19/180, 10.6%) (RR 0.72, 95% CI = 0.36 to 1.45, p = 0.38). CONCLUSIONS: Out-of-hospital cardiac arrest survival in suburban and rural Indiana did not improve after police were equipped with AEDs, likely related to poor police response.

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OBJECTIVES: The goal of this study was to compare T-wave alternans (TWA), signal-averaged electrocardiography (SAECG) and programmed ventricular stimulation (EPS) for arrhythmia risk stratification in patients undergoing electrophysiology study. BACKGROUND: Accurate identification of patients at increased risk for sustained ventricular arrhythmias is critical to prevent sudden cardiac death. T-wave alternans is a heart rate dependent measure of repolarization that correlates with arrhythmia vulnerability in animal and human studies. Signal-averaged electrocardiography and EPS are more established tests used for risk stratification. METHODS: This was a prospective, multicenter trial of 313 patients in sinus rhythm who were undergoing electrophysiologic study. T-wave alternans, assessed with bicycle ergometry, and SAECG were measured before EPS. The primary end point was sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation or appropriate implantable defibrillator (ICD) therapy, and the secondary end point was any of these arrhythmias or all-cause mortality. RESULTS: Kaplan-Meier survival analysis of the primary end point showed that TWA predicted events with a relative risk of 10.9, EPS had a relative risk of 7.1 and SAECG had a relative risk of 4.5. The relative risks for the secondary end point were 13.9, 4.7 and 3.3, respectively (p < 0.05). Multivariate analysis of 11 clinical parameters identified only TWA and EPS as independent predictors of events. In the prespecified subgroup with known or suspected ventricular arrhythmias, TWA predicted primary end points with a relative risk of 6.1 and secondary end points with a relative risk of 8.0. CONCLUSIONS: T-wave alternans is a strong independent predictor of spontaneous ventricular arrhythmias or death. It performed as well as programmed stimulation and better than SAECG in risk stratifying patients for life-threatening arrhythmias.

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INTRODUCTION: Testing for the presence of microvolt T wave alternans (TWA) is useful for arrhythmic risk stratification. Whether antiarrhythmic pharmacotherapy affects the presence of TWA is unknown. We tested whether patients with known ventricular tachyarrhythmias who were receiving amiodarone were less likely to manifest TWA as compared with those not receiving amiodarone. METHODS AND RESULTS: Forty-four patients with a history of ventricular tachyarrhythmias and an implantable cardioverter defibrillator (ICD) implanted at least 1 month earlier underwent TWA testing. In this group, 14 patients were receiving amiodarone and 30 were not. Indeterminate test results occurred in 13 patients without a significant difference in those receiving or not receiving amiodarone. In the 31 patients with determinate TWA testing, a positive test was less likely in those receiving amiodarone (1 of 9 [11%]) as compared with those not receiving amiodarone (14 of 22 [64%]; P = 0.04). During a follow-up period averaging 0.9 +/- 0.2 years, the presence of TWA (P = 0.04) and decreased left ventricular ejection fraction (P = 0.05) predicted appropriate ICD therapy for ventricular tachyarrhythmias. CONCLUSION: The prevalence of TWA was decreased in a chronic ventricular tachyarrhythmic population receiving amiodarone as compared with a population not receiving amiodarone.

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BACKGROUND: In patients with implantable cardioverter-defibrillators (ICDs). inappropriate shocks have been reported with exposure to electronic article surveillance systems. The risk to patients with ICDs of walking through or lingering near surveillance systems requires further investigation. METHODS AND RESULTS: We evaluated the response in ICD function in 170 subjects during a 10- to 15-second midgate walk-through of and during extreme (2 minutes within 6 in of the gate) exposure to 3 common article surveillance systems. Complete testing was done in 169 subjects. During a 10- to 15-second (very slow) walk-through of the 3 surveillance systems, no interactions were observed that would negatively affect ICD function. During extreme exposure (169 subjects) and during extreme exposure and pacing via the ICD (126 subjects), interactions between the ICD and the article surveillance systems were observed in 19 subjects. In 7 subjects, this interaction was clinically relevant and would have likely (3 subjects) and possibly (4 subjects) resulted in ICD shocks. In 12 subjects, the interaction was minor. CONCLUSIONS: It is safe for a patient with an ICD to walk through electronic article surveillance systems. Lingering in a surveillance system may result in an inappropriate ICD shock.

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Loss of ventricular output resulting from an unexpected software error in a dual chamber implantable cardioverter defibrillator (ICD) is reported. A 70-year-old man with a dual chamber ICD implanted for a history of cardiac arrest and infra-Hisian block presented with acute onset of dizziness. He was found to have loss of ventricular output due to an internal software problem. The problem was corrected by software reprogramming via the programmer. This malfunction exemplifies the potential ability to correct current-generation ICD software problems noninvasively, thus avoiding the need for replacement.

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Catheter mapping and radiofrequency ablation of postinfarct sustained ventricular tachycardia (VT) remain one of the greatest challenges for the electrophysiologist. Although there were no major breakthroughs during the past year, several refinements and clarifications of existing mapping criteria were published. In addition, initial reports appeared describing new mapping systems and ablation technologies that may significantly impact the way ablation studies are performed as well as the way in which they affect success rates. Uncertainties remain as to how effective catheter ablation will be as a longterm cure for this type of VT. For the foreseeable future, catheter ablation in postinfarct VT will remain adjunctive rather than primary therapy.

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Implantable cardioverter-defibrillators are commonly used in patients who have life-threatening ventricular arrhythmias. With these implanted electronic devices, bradyarrhythmias and tachyarrhythmias can be recognized promptly and treated with electrical pacing, cardioversion or defibrillation. Implantable cardioverter-defibrillators have been shown to substantially reduce the incidence of sudden cardiac death in patients with known life-threatening ventricular arrhythmias. Their role in the primary prevention of sudden cardiac death in patients at high risk for ventricular arrhythmias is being evaluated. Technologic advances have allowed transvenous implantation of cardiac leads, obviating the need for open heart surgery and thereby lowering the risk of perioperative morbidity and mortality. Most electrical therapies are triggered appropriately to treat ventricular tachycardia/fibrillation. Inappropriate discharges may occur secondary to supraventricular causes of tachycardia, environmental interference from electromagnetic devices or malfunction of the cardioverter-defibrillator. All episodes of discharge merit investigation. With recurrent or frequent discharges, prompt evaluation and hospitalization are often necessary.

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INTRODUCTION: Reverse rate-dependence, a lessening in Class III antiarrhythmic agent action potential duration (APD) prolongation as heart rate is increased, has been proposed to be related to an incomplete deactivation of the slow component (IKs) of the delayed rectifier K+ current (IK). The rate-dependent properties of block of IK by azimilide were compared to E-4031, which selectively blocks the rapid component (IKr) of IK, in guinea pig ventricular muscle. METHODS AND RESULTS: Azimilide prolonged APD in isolated papillary muscles in a concentration-dependent manner and to a greater degree than E-4031. Both agents prolonged APD less at fast than slow rates, consistent with a similar reverse rate-dependent effect. Isolation of azimilide block of IKs by subtraction of APD during E-4031 plus azimilide from E-4031 alone revealed rate-independent prolongation of APD. In voltage clamp experiments on single ventricular myocytes, activation of IKs was similar following 30 seconds of conditioning pulses of physiological duration (125 to 200 msec) with either a fast (cycle length 250 msec) or slow (cycle length 2000 msec) rate. The block of IKs by azimilide 3 microM was greater after a fast conditioning pulse train. CONCLUSIONS: Selective block of IKs prolongs APD in a rate-independent manner. In voltage clamped myocytes, no evidence of a rate-dependent accumulation of IKs was observed. These findings support a mechanism of reverse rate-dependent APD prolongation by Class III antiarrhythmic agents that block IKr independent of IKs.

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We surveyed the use of implantable cardioverter-defibrillators in patients with congenital long QT syndrome. The implantable cardioverter-defibrillator was used primarily in high-risk persons and appeared safe and effective over a mean 31-month follow-up.

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OBJECTIVES: The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. METHODS: Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patch clamp procedure during perfusion of normotonic, normotonic with addition of E-4031, and hypotonic plus E-4031 solutions. RESULTS: Cell swelling leading to membrane stretch of myocytes in the whole-cell recording configuration occurred with hypotonic solution perfusion. APD, prolonged by E-4031, was reduced to less than control value with hypotonic-induced stretch. Evaluation of whole-cell currents after hypotonic-induced stretch revealed no significant changes in the L-type Ca2+ current, inward rectifier K+ current or the rapid component of the delayed rectifier K+ current. The slow component of the delayed rectifier K+ current (IKs) was upregulated and a stretch-induced CI- current was activated in hypotonic solutions. The hypotonic-induced modulation of these currents was not effected by protein kinase A or C inhibition. CONCLUSIONS: Hypotonic-induced stretch shortens APD and counteracts the effects of E-4031. This APD shortening is secondary to upregulation of IKs and activation of a stretch-induced Cl- current.

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Phentolamine and related imidazolines inhibit KATP channel activity in the pancreatic beta cell. In the present study, the effects of several imidazoline-based compounds were examined upon KATP channel activity in guinea pig ventricular myocytes. Phentolamine produced a potent inhibition of KATP channel activity when examined in either excised inside-out patches or in the whole-cell configuration. This effect was unrelated to phentolamine's ability to antagonise alpha-adrenoceptors since the nonselective alpha-adrenoceptor antagonists, benextramine and phenoxybenzamine, failed to affect channel activity. Furthermore, the alpha-adrenoceptor agonist clonidine together with several related imidazolines inhibited channel activity. This suggests that imidazoline compounds modulate KATP channel activity in guinea pig ventricular myocytes and this may have clinical implications for the use of such agents as hypoglycemic drugs.

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BACKGROUND: Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic beta-adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant beta-adrenergic blocking effect, before and after isoproterenol infusion. METHODS AND RESULTS: Action potential duration at 90% repolarization (APD90) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10(-4) mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD90 for d-sotalol and dl-sotalol over control were 10.9 +/- 2.5 to 23.7 +/- 4.8 ms and 27.9 +/- 4.0 to 39.0 +/- 5.6 ms, respectively. APD90 shortened to less than control in papillary muscles treated with d-sotalol but not dl-sotalol on addition of isoproterenol 10(-6) mol/L: -31.2 +/- 3.5 to -18.3 +/- 4.8 ms and 10.5 +/- 3.6 to 33.3 +/- 7.8 ms, respectively, P < .003. Single guinea pig ventricular myocytes were studied by the whole-cell patch clamp method. Time-dependent (Iout) and total (Itot) outward current in response to a 300-ms pulse to 20 mV and tail current (Itail) to -35 mV were measured after Ca2+ channel block and Na+ channel inactivation. Iout, Itail, and Itot were reduced in myocytes perfused with d-sotalol and dl-sotalol 10(-4) mol/L: Iout, -36.1 +/- 4.1%, -40.5 +/- 3.3%; Itail, -59.3 +/- 4.6%, -62.2 +/- 11.1%; Itot, -27.3 +/- 4.3%, -50.0 +/- 11.8%. Iout and Itot increased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10(-6) mol/L: Iout, 100.3 +/- 20.6%, 11.3 +/- 7.6%, P = .002; Itot, 86.8 +/- 39.2%, -41.1 +/- 20.9%, P = .01. Itail tended to increase more in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol, but the difference was not significant (-9.1 +/- 13.5%, -28.0 +/- 9.0%). CONCLUSIONS: The beta-adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence.

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Slowly activating, voltage-dependent IsK channels were expressed in Xenopus oocytes after injection of rat IsK protein cRNA and recorded with the two-microelectrode voltage-clamp technique. The IsK currents were inhibited by the new class III antiarrhythmic drugs NE-10064 and NE-10133. These compounds were equally potent in inhibiting a slowly activating potassium current (IKs) in guinea pig ventricular myocytes. No effects of these compounds could be observed on several other cloned delayed rectifier potassium channels, nor did they affect the inward rectifier current, IK1, in guinea pig cardiac myocytes at the concentrations tested. The blockade of IsK channels may contribute to the class III antiarrhythmic efficacy of these novel antiarrhythmics.

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A case of bilateral internal mammary artery-to-pulmonary artery fistulas presenting as recurrent angina late after revascularization is described. Objective evidence of ischemia was documented using stress electrocardiography and thallium-201 scintigraphy. The patient was managed conservatively to date with medical therapy. Fistula formation may complicate internal mammary artery bypass grafting and should be considered as a potential cause of recurrent angina.

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