Conversion efficacy and safety of intravenous ibutilide compared with intravenous procainamide in patients with atrial flutter or fibrillation

OBJECTIVES: This multicenter study compared the efficacy and safety of ibutilide versus procainamide for conversion of recent-onset atrial flutter or fibrillation. BACKGROUND: Ibutilide fumarate is an intravenous (IV) class III antiarrhythmic agent that has been shown to be significantly more effective than placebo in the pharmacologic conversion of atrial flutter and fibrillation to sinus rhythm. Procainamide is commonly used for conversion of recent-onset atrial fibrillation to normal sinus rhythm. METHODS: One hundred twenty-seven patients (age range 22 to 92 years) with atrial flutter or fibrillation of 3 h to 90 days' (mean 21 days) duration were randomized to receive either two 10-min IV infusions of 1 mg of ibutilide fumarate, separated by a 10-min infusion of 5% dextrose in sterile water, or three successive 10-min IV infusions of 400 mg of procainamide hydrochloride. RESULTS: Of the 127 patients, 120 were evaluated for efficacy: 35 (58.3%) of 60 in the ibutilide group compared with 11 (18.3%) of 60 in the procainamide group had successful termination within 1.5 h of treatment (p < 0.0001). Seven patients were found to have violated the protocol and were not included in the final evaluation. In the patients with atrial flutter, ibutilide had a significantly higher success rate than procainamide (76% [13 of 17] vs. 14% [3 of 22], p=0.001). Similarly, in the atrial fibrillation group, ibutilide had a significantly higher success rate than procainamide (51% [22 of 43] vs. 21% [8 of 38], p=0.005). One patient who received ibutilide, which was found to be a protocol violation, had sustained polymorphic ventricular tachycardia requiring direct current cardioversion. Seven patients who received procainamide became hypotensive. CONCLUSIONS: This study establishes the superior efficacy of ibutilide over procainamide when administered to patients to convert either atrial fibrillation or atrial flutter to sinus rhythm. Hypotension was the major adverse effect seen with procainamide. A low incidence of serious proarrhythmia was seen with the administration of ibutilide occurring at the end of infusion.     

Atrial electrograms and activation sequences in the transition between atrial fibrillation and atrial flutter

INTRODUCTION: The electrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFL), which was right atrial (RA) arrhythmia, and sought to investigate intra-atrial electrograms and activation sequences in the transition between AF and AFL. METHODS AND RESULTS: Intra-atrial electrograms and activation sequences in the RA free wall and the septum were evaluated in the transition between AF and AFL in seven patients without organic heart disease (all men; mean age 57+/-11 years). In five episodes of the conversion of AFL into AF, the AFL cycle length was shortened (from 211+/-6 msec in stable AFL to 190+/-15 msec before the conversion, P, 0.001). Interruption of the AFL wavefront and an abrupt activation sequential change induced by a premature atrial impulse resulted in fractionation and disorganization of the septal electrograms. During sustained AF, septal electrograms were persistently fractionated with disorganized activation sequences. However, the RA free-wall electrograms were organized, and the activation sequence was predominantly craniocaudal rather than caudocranial throughout AF. In 12 episodes of the conversion of AF into AFL, the AF cycle length measured in the RA free wall increased (from 165+/-26 msec at the onset of AF to 180+/-24 msec before the conversion, P, 0.001). AFL resumed when fractionated septal electrograms were separated and organized to the caudocranial direction, despite the RA free-wall electrograms remaining discrete and sharp with an isoelectric line. CONCLUSION: Changes of the electrogram and activation sequence in the atrial septum played an important role in the transition between AF and AFL.     

Pharmacologic control of heart rate in atrial fibrillation

Atrial fibrillation is associated with a resting heart rate in excess of age-matched subjects in sinus rhythm, and there is an additional steep rise in rate during exertion. This article reviews the factors responsible for this tachycardia, the pharmacologic agents commonly used for heart rate control, and the effects of atrial antiarrhythmic agents on the heart rate during paroxysmal atrial fibrillation.     

Radiofrequency catheter ablation of atrial flutter and atrial fibrillation

The existence of a physiological integration between the immune and endocrine systems has long been recognized. In spite of the abundant literature data on the presence of cells of the immune system in the testis, mast cells and eosinophil leukocytes have received little attention. We have studied the presence, distribution and numbers of mast cells and eosinophils in the testes of 12 mammalian species. Mast cells were frequently found in equine (stallion, ass and mule) and human testis, whereas eosinophils were nearly absent. On the contrary, eosinophils were abundant in the hare testis, while mast cells were lacking. Both cells types were present in high numbers in swine (wild and domestic boar) testis. Otherwise, mast cells and eosinophils were absent from the testicular parenchyma of several species (rat, dog, cat, bull and deer), although they were present, in most cases, around blood vessels in the tunica albuginea. The presence of high numbers of mast cells and/or eosinophil leukocytes in the testicular parenchyma of some species suggest a role for these cells in local regulatory pathways.     

Cardiac troponin T does not increase after electrical cardioversion for atrial fibrillation or atrial flutter

BACKGROUND: Leishmaniasis is an important protozoan disease. In the Americas it is produced by several species of the genus Leishmania, transmitted by sand flies of the genus Lutzomyia. Disease spectrum ranges from cutaneous ulceration to more serious involvement of oronasal mucosa that may progress to destruction of central structures of the face and to the life-threatening visceral forms. Leishmania Viannia braziliensis is the most widespread species in Brazil and is often associated with mucosal involvement. Cutaneous lesions are commonly localised in uncovered areas of the body. Genital lesions are rare. MATERIALS AND METHODS: A patient with an ulcerated lesion of the glans penis, followed subsequently by mucosal lesions of the nasal cavity and palate, is presented. Diagnostic procedures were: leishmanin skin test (Montenegro's test) and biopsy of the ulcer border processed for histopathological examination and culture in NNN medium. RESULTS: Leishmanin skin test was positive. Histopathology showed a granulomatous infiltrate containing some parasites. Culture was positive for Leishmania sp., and was later identified by zymodeme analysis and monoclonal antibodies as L.(V.) braziliensis. The patient was treated with pentavalent antimony at the dose of 10 (mg/kg)/day for 30 days and the lesions healed. COMMENTS AND CONCLUSIONS: In men, especially over 50 years of age, ulceration of the glans penis is highly suggestive of carcinoma. Precise differential diagnosis is imperative. A lesion, such as the one reported, may cause diagnostic difficulties when it presents in countries different from the source, where the condition is very uncommon. This is increasingly frequent in the current era of widespread air travel.     

Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter

The results of nineteen semiconstrained modified Coonrad-Morrey total elbow arthroplasties performed in nineteen patients to treat instability were evaluated at an average of seventy-two months (range, twenty-five to 128 months) postoperatively. Preoperatively, all patients had either a flail elbow or gross instability of the elbow that prevented useful function of the extremity. The instability of sixteen elbows was the result of a traumatic injury or of the treatment of such an injury. The most recent result was satisfactory for sixteen elbows and unsatisfactory for three. The average overall Mayo elbow performance score increased from 44 points preoperatively to 86 points postoperatively. At the most recent follow-up examination, no elbow was unstable. The average arc of flexion was from 25 degrees (range, 0 to 60 degrees) to 128 degrees (range, 30 to 142 degrees), which represented a 58-degree increase from the preoperative average arc. Sixteen patients had little or no pain after the arthroplasty. There were four complications in four patients. Three complications (loosening of the humeral component in one patient and a fracture of the ulnar component in two) occurred postoperatively; all three were treated with a revision procedure. The other complication (a fracture of the olecranon) occurred intraoperatively and was treated with tension-band fixation; the most recent outcome was not affected. Radiographically, one patient had complete (type-V) radiolucency about the humeral component. None of the nine patients for whom true anteroposterior radiographs were available had evidence of wear of the bushings. The bone graft behind the anterior flange of the humeral prosthesis was mature in fourteen elbows, incomplete in two, and resorbed in two. One patient was excluded from this analysis because radiographs were not available. Instability of the elbow resulting in the inability to use the extremity is a challenging clinical situation. However, in patients who are more than sixty years old and in selected patients who are less than sixty years old but who have extensive loss of bone as a result of severe injury, have had multiple operations, or have rheumatoid arthritis, total elbow arthroplasty with a linked, semiconstrained prosthesis reestablishes a mobile, stable joint without premature loosening or failure of the components. In our experience, the use of customized implants, maintenance of the muscular attachments to the epicondyles, and reconstruction of the epicondyles to the implant were unnecessary.     

Fatality due to intravenous diltiazem for acute ventricular rate control

Progressive, sustained bradycardia resulting in asystole and subsequent death is reported in a 70-year-old woman with hyperkalemia and suspected digoxin toxicity following a 0.25 mg/kg intravenous diltiazem dose for treatment of atrial fibrillation with a rapid ventricular response. The possible pharmacodynamic and pharmacokinetic interactions between diltiazem, digoxin, and an elevated plasma potassium concentration are discussed and related to the outcome of the case. The routine practice of concomitant administration of diltiazem for rapid ventricular rate control and digoxin for long-term control may be dangerous in a subset of patients.     

Electrical cardioversion of atrial fibrillation or flutter with conscious sedation in the age of cost containment

OBJECTIVE: To determine if there is a significant difference in the degree of pelvic organ prolapse assigned during examination in the standing position compared with the dorsal lithotomy position with the patient performing maximal Valsalva maneuver. METHODS: Fifty-one women with symptoms of pelvic organ prolapse were examined in both the dorsal lithotomy position, while performing maximal Valsalva, and in the standing position at the same visit by one of two examiners. Nine site-specific measures and summary stages were recorded, as outlined by the International Continence Society's classification system for pelvic organ prolapse. The data were analyzed by Wilcoxon signed-rank test and correlation coefficients. RESULTS: The mean age was 52 +/- 15 years. Excellent correlation was noted between all six points representing the vaginal prolapse. The R values for point Aa were 0.97, Ba 0.96, C 0.98, Ap 0.97, Bp 0.96, and D 0.97. The total vaginal length, perineal body, and genital hiatus measurements were performed in the dorsal lithotomy position with the patient at rest and were not repeated. The stages were identical in 48 of 51 patients. The average stage in the dorsal lithotomy position was 2.3 and in the standing position, 2.3. There was no statistically significant difference between the stage or any of the measured points in the dorsal lithotomy and standing examinations. CONCLUSION: The degree of pelvic organ prolapse can be assessed adequately in the dorsal lithotomy position with the patient performing maximal Valsalva. It is not necessary to routinely repeat the examination in the standing position.     

Spatiotemporal periodicity during atrial fibrillation in the isolated sheep heart

BACKGROUND: The activation patterns that underlie the irregular electrical activity during atrial fibrillation (AF) have traditionally been described as disorganized or random. Recent studies, based predominantly on statistical methods, have provided evidence that AF is spatially organized. The objective of this study was to demonstrate the presence of spatial and temporal periodicity during AF. METHODS AND RESULTS: We used a combination of high-resolution video imaging, ECG recordings, and spectral analysis to identify sequential wave fronts with temporal periodicity and similar spatial patterns of propagation during 20 episodes of AF in 6 Langendorff-perfused sheep hearts. Spectral analysis of AF demonstrated multiple narrow-band peaks with a single dominant peak in all cases (mean, 9.4+/-2.6 Hz; cycle length, 112+/-26 ms). Evidence of spatiotemporal periodicity was found in 12 of 20 optical recordings of the right atrium (RA) and in all (n=19) recordings of the left atrium (LA). The cycle length of spatiotemporal periodic waves correlated with the dominant frequency of their respective optical pseudo-ECGs (LA: R2=0.99, slope=0.94 [95% CI, 0.88 to 0.99]; RA: R2=0.97, slope=0.92 [95% CI, 0.80 to 1.03]). The dominant frequency of the LA pseudo-ECG alone correlated with the global bipolar atrial EG (R2=0.76, slope=0.75 [95% CI, 0.52 to 0.99]). In specific examples, sources of periodic activity were seen as rotors in the epicardial sheet or as periodic breakthroughs that most likely represented transmural pectinate muscle reentry. However, in the majority of cases, periodic waves were seen to enter the mapping area from the edge of the field of view. CONCLUSIONS: Reentry in anatomically or functionally determined circuits forms the basis of spatiotemporal periodic activity during AF. The cycle length of sources in the LA determines the dominant peak in the frequency spectra in this experimental model of AF.     

Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis

Pooled data from 32 studies were reviewed to assess the timing of thrombolic complications after cardioversion of atrial fibrillation or flutter. We found that 98% of embolic episodes occurred within 10 days of cardioversion.     

Altered protein binding of quinidine in patients with atrial fibrillation and flutter

BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine that plays a role in transplant rejection. We tested the hypothesis that IL-6 levels in serum or urine could be of value in predicting acute and chronic allograft rejection. Furthermore, we examined whether or not such levels reflected IL-6 expression in the kidney. METHODS: We measured IL-6 and IL-6 soluble receptor (IL-6sR) in serum and urine of 145 transplant patients and 20 normal controls. In parallel, we studied 108 renal biopsies. IL-6 was measured with a bioassay system using an IL-6 dependent cell line. IL-6sR was measured with enzyme-linked immunosorbent assay. The biopsies were examined for IL-6 and IL-6 receptor (IL-6R) expression with immunohistochemistry. RESULTS: Rejection episodes occurring within 2 months of transplantation were accompanied by elevated IL-6 concentrations in serum (17 +/- 4.8 pg/ml, P < 0.05) and urine (114 +/- 27 pg/ml, P < 0.005), compared to controls. These values returned towards baseline (0-5 pg/ml) after successful rejection treatment. The sensitivity of urine measurements was much higher (93%) than serum (54%). The specificity in serum (70%) and urine (60%) was reduced by infection, acute tubular necrosis, and antithymocyte globulin treatment. Serum and urine IL-6sR values did not correlate with rejection. In biopsy tissue, IL-6 and IL-6R were both elevated during rejection. Especially, mononuclear cells within the interstitial infiltrate stained positive. However, the amount of IL-6 positive cells did not correlate with peripheral IL-6 concentrations. CONCLUSIONS: Urine but not serum IL-6 values are sensitive indicators of rejection; however, they are confounded by infection, acute tubular necrosis, and certain antirejection treatments. These features limit their usefulness.     

Magnesium reversal of digoxin-facilitated ventricular rate during atrial fibrillation in the Wolff-Parkinson-White syndrome

The purpose of this investigation was to determine whether pyrophosphate, the anticalculus component of tartar-control dentifrices, exerts antimicrobial activity against oral bacteria commonly found in supragingival plaque. Minimal inhibitory concentrations of pyrophosphate were determined for Streptococcus sanguis, Streptococcus mutans (serotype c), Actinomyces viscosus and Actinomyces naeslundii. All of the bacteria tested were susceptible to pyrophosphate with identical minimal inhibitory concentrations of 0.67% wt/vol (25 mM). Bactericidal kinetics assays revealed that both S. mutans and A. viscosus were killed by pyrophosphate, with the latter being considerably more susceptible. The mechanism of killing was not due to high ionic strength, as comparable controls showed no loss in numbers of viable cells. Brief exposure (two 5-min incubations) of S. mutans to pyrophosphate and sodium dodecyl sulfate caused pronounced inhibition of growth over the 24-h test period. Under the constraints of the conditions used, these studies indicate that pyrophosphate and sodium dodecyl sulfate can substantially inhibit the growth of oral bacteria. These compounds may affect the oral microflora of patients who routinely use tartar-control dentifrices and mouthrinses.     

Effects of beta-blockade on atrial and atrioventricular nodal refractoriness, and atrial fibrillatory rate during atrial fibrillation in pigs

Despite their widespread use in atrial fibrillation, the effects of beta-adrenoceptor blockers on atrial and atrioventricular (AV) nodal refractoriness, and atrial fibrillatory rate during atrial fibrillation have been incompletely characterised. In particular, it is unknown whether additional sodium channel (class I) blocking effects play a role. Effects of bisoprolol (no class I effect) and metoprolol (mild class I effect) were therefore compared in 12 open-chest pigs. Atrial and AV-nodal effective refractory periods were determined at pacing cycle length 500 ms and 300 ms. Atrial fibrillation was then induced by premature stimulation and topical application of metacholine, and atrial fibrillatory intervals and ventricular intervals were recorded. After resumption of sinus rhythm, bisoprolol 0.1 mg/kg or metoprolol 0.3 mg/kg was administered, and measurements were repeated. Also, effects on plasma catecholamines and signal-averaged QRS duration were determined. Both bisoprolol and metoprolol prolonged atrial and AV-nodal effective refractory periods at both pacing cycle lengths, however, no differences were noted between the two drugs. No significant effects were observed on atrial and ventricular intervals during atrial fibrillation. Plasma catecholamines were low and unaffected by either drug, as was the QRS duration. It is concluded that the mild class I effect of metoprolol does not play a role in atrial fibrillation. Also, the results confirm the clinical notion that beta-blockers exert insignificant effects during atrial fibrillation in the setting of low sympathetic tone.     

Catheter ablation for atrial flutter and fibrillation. An effective alternative to medical therapy

Atrial flutter and atrial fibrillation are common arrhythmias that can be difficult to manage clinically. In many patients, these conditions are refractory to pharmacologic therapy because of drug failure or intolerance. Radiofrequency catheter ablation may be a reasonable alternative in patients with typical atrial flutter. The procedure has a high initial success rate and a low complication rate. However, recurrence after ablation is common, and a second treatment session may be needed. In selected patients with atrial fibrillation, radiofrequency ablation can be useful for rate control. However, its use in curing chronic fibrillation is still experimental. The procedure involves insertion of a pacemaker, anticoagulation therapy is still needed in most patients, and the need for antiarrhythmic medication may not be obviated.