C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) may persist due to structural changes in the atria that are promoted by inflammation. C-reactive protein (CRP), a marker of systemic inflammation, predicts cardiovascular events and stroke, a common sequela of AF. We hypothesized that CRP is elevated in patients with atrial arrhythmias. METHODS AND RESULTS: Using a case-control study design, CRP in 131 patients with atrial arrhythmias was compared with CRP in 71 control patients. Among arrhythmia patients, 6 had frequent atrial ectopy or tachycardia, 86 had paroxysmal AF, 39 had persistent AF lasting >30 days, and 70 had lone arrhythmias. CRP was higher in arrhythmia than in control patients (median, 0.21 versus 0.096 mg/dL; P<0.001). Arrhythmia patients in AF within 24 hours before sampling had higher CRP than those in sinus rhythm (0.30 versus 0.15 mg/dL; P<0.001). CRP in controls was not different than in patients with atrial ectopy or tachycardia. Lone arrhythmia patients had a CRP of 0.21 mg/dL, which was not significantly lower than arrhythmia patients with structural heart disease (CRP, 0.23 mg/dL) but higher than controls (P=0.002). Persistent AF patients had a higher CRP (0.34 mg/dL) than paroxysmal AF patients (0.18 mg/dL; P=0.008); both groups had higher CRP levels than controls (P

Reasons for prolonged or failed attempts at radiofrequency catheter ablation of accessory pathways.

OBJECTIVES: The purpose of this study was to categorize the reasons for a prolonged or failed procedure in a series of patients undergoing catheter ablation of an accessory pathway. BACKGROUND: Radiofrequency ablation of accessory pathways at times requires a lengthy procedure or a second ablation session, or both, and not prior studies have systematically investigated the reasons for this. METHODS: In a consecutive series of 619 patients undergoing catheter ablation of an accessory pathway, the mean ablation time +/- SD was 68 +/- 64 min. The subjects of this study were 14 patients who had an ablation time >2 SD greater than the mean (>196 min) and 51 patients who required a second ablation session for a successful outcome. The accessory pathway in the 65 patients in this study was located in the right free wall in 19 patients (29%), septum in 14 (22%) and left free wall in 32 (49%). RESULTS: The primary reasons for a lengthy or failed ablation attempt were 1) inability to position the ablation catheter at the effective target site (16 patients, 25%); 2) instability of the ablation catheter or inadequate tissue contact at the target site, or both (15 patients, 23%); 3) mapping error due to an oblique course of the accessory pathway (7 patients, 11%); 4) failure to recognize a posteroseptal accessory pathway as being left-sided instead of right-sided (4 patients, 6%); 5) other errors in accessory pathway localization (6 patients, 9%); 6) epicardial location of the accessory pathway (5 patients, 8%); 7) recurrent atrial fibrillation (2 patients, 3%); 8) occurrence of a complication (2 patients, 3%); 9) unusual right-sided accessory pathway that inserted in the anterior right ventricle, 2 cm away from the lateral tricuspid annulus (1 patient, 1.5%); and 10) unexplained factors (7 patients, 11%). The most common effective strategies employed to achieve a successful outcome in these patients were 1) substitution of a more experienced operator; 2) use of ablation catheters of varying configurations; 3) switching from a retrograde aortic to a trans-septal approach; 4) switching from an inferior to a superior vena caval approach; 5) use of a 60-cm guiding sheath; 6) detailed mapping of the atrial or ventricular insertion of the accessory pathway; and 7) searching within the coronary sinus for a presumed accessory pathway potential. CONCLUSIONS: A lengthy or failed attempt at catheter ablation of an accessory pathway may be due to a variety of reasons, the most common of which are problems related to some aspect of catheter manipulation and errors in accessory pathway localization. Knowledge of the most common reasons for a lengthy or ineffective procedure may facilitate successful outcome of accessory pathway ablation.

Effect of shock polarity on ventricular defibrillation threshold using a transvenous lead system.

OBJECTIVES: The purpose of this study was to determine whether the polarity of a monophasic shock used with a transvenous lead system affects the defibrillation threshold. BACKGROUND: The ability to implant an automatic defibrillator depends on achieving an adequate defibrillation threshold. METHODS: A transvenous defibrillation lead with distal and proximal shocking electrodes was used in this study. In 29 consecutive patients, the defibrillation threshold, using a stepdown protocol was determined twice in random order: 1) with the distal coil as the anode, and 2) with the polarity reversed. Only the 20 patients in whom an adequate defibrillation threshold could be obtained with the transvenous lead alone were included in this study. These patients were 61 +/- 14 years old (mean +/- SD) and had a mean ejection fraction of 28 +/- 12%. RESULTS: The mean defibrillation threshold was 11.5 +/- 5.0 J with the distal coil as the anode versus 16.9 +/- 7.7 J with the distal coil as the cathode (p = 0.04). The defibrillation threshold was lower by a mean of 9 +/- 7 J with the former configuration in 14 patients and was lower by a mean of 7 +/- 6 J with the latter configuration in 3 patients; in 3 patients it was the same with both configurations. Use of a subcutaneous patch was avoided in five patients by utilizing the distal electrode as the anode. CONCLUSIONS: Defibrillation thresholds with monophasic shocks are approximately 30% lower with the distal electrode as the anode. The use of anodal shocks may obviate the need for a subcutaneous patch and allow more frequent implantation of a transvenous lead system.

Effect of first-phase polarity of biphasic shocks on defibrillation threshold with a single transvenous lead system.

OBJECTIVES: The purpose of this study was to determine whether the polarity of the first phase of a biphasic shock affects the defibrillation threshold. BACKGROUND: The polarity of a monophasic shock has been shown to affect the defibrillation threshold. METHODS: A transvenous defibrillation lead with distal and proximal shocking electrodes was used in this study. In 15 consecutive patients, the defibrillation threshold was determined twice using a step-down protocol, in random order: with the distal coil as the anode for the initial phase (anodal biphasic shock) and with the polarity reversed (cathodal biphasic shock). The power to detect a 5.0-J difference in this study is 0.96. These patients were 61 +/- 11 years old (mean +/- SD), and the mean left ventricular ejection fraction was 0.32 +/- 0.10. RESULTS: Mean defibrillation threshold using anodal biphasic shocks was 9.9 +/- 4.8 J, compared with 9.5 +/- 4.2 J using cathodal biphasic shocks (p = 0.8). In three patients the defibrillation threshold was lower by a mean of 6.3 +/- 2.9 J with the former configuration; in three patients the defibrillation threshold was lower by a mean of 6.7 +/- 2.5 J with the latter configuration; and in nine patients it was the same. Using the standard cathodal configuration, a defibrillation threshold < or = 10 J was obtained in approximately 70% of patients, and a subcutaneous patch was not required in any patient. CONCLUSIONS: The polarity of the first phase of a biphasic shock used with a single transvenous lead does not affect the defibrillation threshold.

Is hospital admission for initiation of antiarrhythmic therapy with sotalol for atrial arrhythmias required? Yield of in-hospital monitoring and prediction of risk for significant arrhythmia complications.

OBJECTIVES: We sought to determine the yield of in-hospital monitoring for detection of significant arrhythmia complications in patients starting sotalol therapy for atrial arrhythmias and to identify factors that might predict safe outpatient initiation. BACKGROUND: The need for hospital admission during initiation of antiarrhythmic therapy has been questioned, particularly for sotalol, with which proarrhythmia may be dose related. METHODS: The records of 120 patients admitted to the hospital for initiation of sotalol therapy were retrospectively reviewed to determine the incidence of significant arrhythmia complications, defined as new or increased ventricular arrhythmias, significant bradycardia or excessive corrected QT (QTc) interval prolongation. RESULTS: Twenty-five patients (20.8%) experienced 35 complications, triggering therapy changes during the hospital period in 21 (17.5%). New or increased ventricular arrhythmias developed in 7 patients (5.8%) (torsade de pointes in 2), significant bradycardia in 20 (16.7%) (rate <40 beats/min in 13, pause >3.0 s in 4, third-degree atrioventricular block in 1, permanent pacemaker implantation in 3) and excessively prolonged QTc intervals in 8 (6.7%) (dosage reduced or discontinued in 6). Time to the earliest detection of complications was 2.1 +/- 2.5 (mean +/- SD) days after initiation of sotalol, with 22 of 25 patients meeting criteria for complications within 3 days of monitoring. Baseline electrocardiographic intervals or absence of heart disease failed to distinguish a low risk group. Multivariate analysis identified absence of a pacemaker as the only significant predictor of arrhythmia complications (p = 0.022). CONCLUSIONS: Because clinically significant complications can be detected with in-hospital monitoring in one of five patients starting sotalol therapy, hospital admission is warranted for initiation of sotalol. Patients without pacemakers are at higher risk for these complications.

Higher energy synchronized external direct current cardioversion for refractory atrial fibrillation.

OBJECTIVES: We sought to evaluate the safety and efficacy of higher energy synchronized cardioversion in patients with atrial fibrillation refractory to standard energy direct current (DC) cardioversion. BACKGROUND: Standard external electrical cardioversion fails to restore sinus rhythm in 5% to 30% of patients with atrial fibrillation. METHODS: Patients with atrial fibrillation who failed to achieve sinus rhythm after at least two attempts at standard external cardioversion with 360 J were included in the study. Two external defibrillators, each connected to its own pair of R-2 patches in the anteroposterior position, were used to deliver a synchronized total of 720 J. RESULTS: Fifty-five patients underwent cardioversion with 720 J. Mean weight was 117 +/- 23 kg (body mass index 48.3 +/- 4.1 kg/m2). Structural heart disease was present in 76% of patients. Mean left ventricular ejection fraction was 45 +/- 12%. Atrial fibrillation was present for over three months in 55% of the patients. Sinus rhythm was achieved in 46 (84%) of the 55 patients. No major complications were observed. No patient developed hemodynamic compromise and no documented cerebrovascular accident occurred within one month after cardioversion. Of the 46 successful cardioversions, 18 patients (39%) remained in sinus rhythm over a mean follow-up of 2.1 months. CONCLUSIONS: External higher energy cardioversion is effective in restoring sinus rhythm in patients with atrial fibrillation refractory to standard energy DC cardioversion. This method is safe and does not result in clinical evidence of myocardial impairment. It may be a useful alternative to internal cardioversion because it could be done within the same setting of the failed standard cardioversion and obviates the need to withhold protective anticoagulation for internal cardioversion.

Neuroprotective effects of early vs. late administration of dantrolene in experimental status epilepticus.

We examined the effects of dantrolene, an inhibitor of intracellular calcium release, on hippocampal neuronal damage associated with 140 min of limbic status epilepticus in the rat. Dantrolene (10 mg/kg i.p.) was administered after either 30 min or 140 min of status epilepticus. Early administration was associated with a significant reduction in the amount of neuronal injury in all hippocampal subregions, while late administration was associated with less neuronal injury in area CA3 only. These findings suggest that a substantial portion of seizure-induced hippocampal injury is associated with release of calcium from intracellular stores, and that early administration of dantrolene may be a useful adjunct to anticonvulsant treatment of status epilepticus.

Comparison of implantation of nonthoracotomy defibrillators in the operating room versus the electrophysiology laboratory.

Implantable cardioverter-defibrillators (ICDs) with nonthoracotomy lead systems are widely available, and are implanted either in the electrophysiology laboratory or the operating room. The purpose of this study was to prospectively evaluate the safety and efficacy of nonthoracotomy ICD implantation in an electrophysiology laboratory versus an operating room. During a 7-month period, 62 consecutive ICDs with nonthoracotomy lead systems were implanted in patients in an electrophysiology laboratory. During the next 10 months, 110 consecutive ICDs were implanted in patients in a surgical operating room. All ICD implantations were performed under general anesthesia by electrophysiologists. There were no differences in age (58 +/- 14 vs 62 +/- 12 years, p = 0.06), gender distribution (p = 0.3), frequency of structural heart disease (97% vs 97%, p = 0.9), ejection fraction (0.31 +/- 0.15 vs 0.29 +/- 0.13, p = 0.3), or presentation with cardiac arrest (65% vs 53%, p = 0.2) between patients undergoing ICD implantation in the electrophysiology laboratory and operating room, respectively. The rate of successful implantation and of complications for systems implanted in the electrophysiology laboratory (95% and 13%, respectively) and in the operating room (98% and 14%, respectively) were similar (p = 0.4 and p = 0.8, respectively). Specifically, the rate of infection (0% vs 4%, p = 0.3) and hematoma formation (2% vs 4%, p = 0.8) were not statistically significantly different. Three patients who had undergone ICD implantation in an operating room died within 30 days. ICDs with nonthoracotomy lead systems can be implanted with a similarly high rate of success and acceptable complication rate in the electrophysiology laboratory and in the operating room.

Electrophysiologic effects of sotalol and amiodarone in patients with sustained monomorphic ventricular tachycardia.

No prospective studies have compared sotalol and amiodarone during electropharmacologic testing. The purpose of this prospective, randomized study was to compare the electrophysiologic effects of sotalol and amiodarone in patients with coronary artery disease and sustained monomorphic ventricular tachycardia (VT). Patients with coronary artery disease and sustained monomorphic VT inducible by programmed stimulation were randomly assigned to receive either sotalol (n = 17) or amiodarone (n = 17). The sotalol dose was titrated to 240 mg twice daily over 7 days. Amiodarone dosing consisted of 600 mg 3 times daily for 10 days. An electrophysiologic test was performed in the baseline state and at the end of the loading regimen. An adequate response was defined as the inability to induce VT or the ability to induce only relatively slow hemodynamically stable VT. During the follow-up electrophysiologic test, 24% of patients taking sotalol and 41% of those taking amiodarone had an adequate response to therapy (p = 0.30). Amiodarone lengthened the mean VT cycle length to a greater degree than sotalol (28% vs 12%, p < 0.01). There were no significant differences in the effects of sotalol and amiodarone on the ventricular effective refractory period. In patients with coronary artery disease, amiodarone and sotalol are similar in efficacy in the treatment of VT as assessed by electropharmacologic testing. The effects of the 2 drugs on ventricular refractoriness are similar, but amiodarone slows VT to a greater extent than sotalol.

QT dispersion in nonsustained ventricular tachycardia and coronary artery disease.

This study examines the relation between QT dispersion and the inducibility of ventricular tachycardia (VT) in 35 consecutive patients with coronary artery disease who underwent electrophysiologic testing for evaluation of nonsustained VT. The mean age of the patients was 66 +/- 9 years (+/- SD) and the mean left ventricular ejection fraction was 0.36 +/- 0.14. In 6 patients in whom sustained, monomorphic VT was inducible by programmed ventricular stimulation, QT dispersion was significantly greater than in the 29 patients in whom VT was not inducible (126 +/- 35 vs 67 +/- 25 ms, p < 0.001). All patients who had a QT dispersion > 120 ms had inducible sustained monomorphic VT, and no patient who had a QT dispersion < 90 ms had inducible VT. The patients who had inducible VT dis not differ significantly from those who did not with regard to age, gender, ejection fraction, RR interval, or mean QT. In conclusion, in patients with coronary artery disease who have nonsustained VT, inducibility of monomorphic VT is associated with an increase in QT dispersion. QT dispersion may be helpful in predicting which patients with nonsustained VT are and are not likely to have inducible VT by programmed stimulation.

Topiramate reduces neuronal injury after experimental status epilepticus.

Prolonged seizures are associated with injury to vulnerable neurons, particularly in the hippocampus. Identification of compounds that attenuate injury after prolonged seizures could be of value in the management of refractory status epilepticus. We hypothesized that topiramate, an anticonvulsant with multiple mechanisms of action, would attenuate hippocampal neuronal injury when given after experimental status epilepticus. Limbic status epilepticus was induced in adult male Wistar rats for 140 min by unilateral hippocampal electrical stimulation. Rats then received intraperitoneal injections of either vehicle (n=6) or topiramate at 20 mg/kg (n=6), 40 mg/kg (n=7) or 80 mg/kg (n=7). Three days later, hippocampal sections were processed for neuronal degeneration using a silver impregnation stain. Seizure-induced damage was assessed by measuring the density of silver staining in hippocampal regions CA1, CA3 and dentate hilus. Administration of topiramate at each dose was associated with a significant reduction in staining density bilaterally in area CA1 and the dentate hilus. Reduction in staining density in area CA3 was seen contralateral to the side of stimulation at the two higher topiramate doses only. The results indicate that administration of topiramate after experimental status epilepticus can attenuate seizure-induced hippocampal neuronal injury.

Management of atrial flutter.

Atrial flutter is a macroreentrant arrhythmia that is associated with cardiovascular and pulmonary disease. In the United States, 200,000 new cases of atrial flutter can be expected to develop every year with a male to female ratio of over 2:1. This arrhythmia is associated with atrial fibrillation in over half the cases. It is also associated with an increased risk of thromboembolic complications, but less than that is seen with atrial fibrillation. The most common form of atrial flutter involves a large reentrant circuit within the right atrium, encircling the tricuspid annulus. Other, less common forms of atrial flutter may involve other anatomic barriers, atriotomy scars, and infarcted areas of the atria. Treatment of atrial flutter often involves electrical cardioversion and/or antiarrhythmic medications. Type I and Type III antiarrhythmic drugs are often used to terminate or prevent recurrent episodes and Type II (beta-blockers) and Type IV (calcium channel blockers) can be used to control the ventricular rate during atrial flutter. However, antiarrhythmic drugs alone control atrial flutter in only 50% to 60% of patients. Since the early 1990s, radiofrequency catheter ablation has been used to interrupt the reentrant circuit and prevent recurrences of atrial flutter. Radiofrequency ablation is acutely successful in over 90% of cases and avoids the long-term toxicity seen with antiarrhythmic drugs. Advanced mapping techniques and newer methods of delivering the radiofrequency lesions are being used to delineate unusual forms of atrial flutter and to minimize fluoroscopic exposure during the procedure.

Static and dynamic responses of carotid sinus baroreceptors in dogs with chronic volume overload.

In this study we determined if there are any alterations in carotid sinus baroreceptor discharge in a model of heart failure in the dog. The left carotid sinus was isolated and perfused at 100 mmHg with a modified Krebs-Henseleit solution. Two groups of dogs were used: a normal group and a group with a chronic aorto-caval fistula (a.v.f.) of up to 20 weeks duration. The a.v.f. group had a significantly elevated heart rate and left ventricular end diastolic pressure as well as an increased arterial pulse pressure compared to normals. However, mean arterial pressure measured in the aortic arch was not significantly different. Carotid sinus pressure-discharge curves were constructed during increases in carotid sinus pressure by steps and by ramps of pressure change up to 200 mmHg/s. Carotid sinus diameter was also measured using sonomicrometer crystals. In six dogs from each group the sodium, potassium and water content of the right carotid sinus was measured. Several parameters of second order polynomial curves that were fitted to the data were compared between the two groups for step and ramp increases in pressure. These included maximum baroreceptor gain, threshold pressure and plateau pressure. Baroreceptor gain was significantly lower in the a.v.f. group for the step and lowest ramp rate pressure changes. Threshold pressure was significantly higher for the a.v.f. group for steps and the three slowest ramp rates. Plateau pressures were significantly higher for the steps and lowest ramp rate. The carotid sinus strain that was produced at any given carotid sinus pressure was not significantly different between the two groups. In addition, there was no difference in the sodium, potassium or water content of the carotid sinus between the two groups. It was concluded that there is a depression of the static discharge characteristics in this model of heart failure which is not due to an alteration in electrolyte or water content or to the compliance of the carotid sinus.

Polymorphic ventricular tachycardia in a woman taking cesium chloride.

A 47-year-old patient presented with syncope and recurrent episodes of polymorphic ventricular tachycardia. She had evidence of prolonged QT interval by ECG and had been taking cesium as a dietary supplement. Correction of the hypokalemia and discontinuation of the cesium resulted in normalization of the QT interval during follow-up with no further recurrence of ventricular arrhythmias. The use of this drug is potentially hazardous as it may induce fatal ventricular arrhythmias.

Improved oxygen delivery during cardiopulmonary resuscitation with interposed abdominal compressions.

The ability of a new modification of cardiopulmonary resuscitation (CPR) to deliver oxygen to tissues was evaluated. The method utilizes standard CPR techniques with the addition of manual abdominal compressions (congruent to 100 mm Hg) interposed between chest compressions, and is termed interposed abdominal compression-CPR (IAC-CPR). Oxygen delivery was measured by a spirometer in a closed circuit designed to permit positive-pressure ventilation synchronized with mechanical chest compression. Ventricular fibrillation was induced electrically in 10 anesthetized dogs. In each dog, trials of IAC-CPR and standard CPR were alternated every five minutes during a 30-minute period. Arterial and central venous blood pressures, oxygen consumption, and Fick cardiac output were monitored. The addition of interposed abdominal compression significantly (P less than .01) increased each of these hemodynamic indicators. Oxygen delivery increased from 4.12 +/- 0.39 ml O2/kg/min during standard CPR to 6.37 +/- 0.35 ml O2/kg/min during IAC-CPR. Arterial systolic blood pressure increased from 67 +/- 5 mm Hg to 90 +/- 5 mm Hg, while diastolic arterial blood pressure rose from 15 +/- 2 mm Hg to 33 +/- 3 mm Hg. Cardiac output increased from 19.9 +/- 2.6 ml/min/kg to 37.5 +/- 2.7 ml/min/kg.

Cardiopulmonary resuscitation with interposed abdominal compression in dogs.

This study was conducted to evaluate the hemodynamic effectiveness of a new modification of cardiopulmonary resuscitation (CPR), termed interposed abdominal compression-CPR (IAC-CPR). IAC-CPR utilizes all the steps of standard CPR with the addition of abdominal compressions interposed during the release phase of chest compression. Ventricular fibrillation was induced electrically in 10 anesthetized dogs, and either IAC-CPR or standard CPR was initiated while arterial and venous blood pressures and cardiac output were monitored. The two CPR methods were alternated every 3 minutes over a period of 30 minutes. The addition of interposed abdominal compressions to standard CPR improved arterial pressures and perfusion in 10 of 10 dogs. Brachial arterial blood pressure averaged 87/32 mm Hg during IAC-CPR vs 58/16 mm Hg during standard CPR. Cardiac output (+/- SE) averaged 24.2 +/- 5.7 ml/min/kg during IAC-CPR vs 13.8 +/- 2.6 ml/min/kg during standard CPR. IAC-SPR requires no extra mechanical equipment, and, if proven effective in human trials, may improve resuscitation success in the field and in the hospital.