Treatment of refractory congestive heart failure by cardiac resynchronization.

The contributions of long-term cardiac resynchronization as a supplemental treatment of refractory congestive heart failure have recently been reported. Several completed studies support the validity of this new therapy, capable of improving quality of life as well as increasing exercise capacity. These gains hinge on a careful patient selection, on the proper placement of the leads, particularly that responsible for left ventricular stimulation, and on an individualized patient follow-up. The results obtained thus fat fully justify considering cardiac resynchronization as an additional option in the treatment management of patients refractory to conventional measures. Ongoing studies should help to further defining its impact on morbidity and overall mortality, as well as the potential role for back up defribillator.

Chemical cardiac sympathetic denervation hampers defibrillation in the dog.

INTRODUCTION: Cardiac defibrillation is influenced by several physical and nonphysical factors. Previous animal studies have shown that beta-adrenergic stimulation facilitates the process of defibrillation. The purpose of this study was to examine the effects of chemical sympathetic denervation on the ability to defibrillate the canine heart. METHODS AND RESULTS: Twelve chronically instrumented dogs underwent serial measurements of the energy required to defibrillate the heart, ten before and after treatment with 50 mg/kg 6-hydroxydopamine (6-OHDA). Two of the animals received 1% ascorbic acid in 0.9% saline solution (the vehicle) only, and three dogs received the vehicle followed several weeks later by 6-OHDA. Following treatment with 6-OHDA, the energy to defibrillate the heart rose from 11.9 +/- 7.4 J (baseline 1) and 14.3 +/- 8.7 J (baseline 2) to 23.3 +/- 10.8 J (P < 0.01 and < 0.05, respectively). In contrast, following saline administration, no significant change was measured in the energy required to defibrillate the heart. After 6-OHDA, 5 of the 10 animals could not be defibrillated versus none of 5 after saline treatment (Chi square 3.750, P = 0.053). In surviving animals, a return of measurements to, or toward, baseline was measured after active treatment. CONCLUSIONS: In this chronically instrumented, closed chest animal model, chemical sympathetic denervation with 6-OHDA hampered the process of cardiac defibrillation. These results support previous observations of a modulating effect of this process by adrenergic activity.

Radiofrequency delivery through a cooled catheter tip allows the creation of larger endomyocardial lesions in the ovine heart.

INTRODUCTION: The delivery of radiofrequency (RF) energy through conventional catheter electrodes is often associated with coagulation necrosis at the tissue-electrode interface, with resultant impedance rise and limited lesion size. This study was performed to examine the effects of catheter tip cooling during RF delivery, to test the hypothesis that such cooling would decrease the likelihood if impedance rise and allow the creation of larger endomyocardial lesions. METHODS AND RESULTS: The experiments were performed in eight open chest, anesthetized sheep. RF lesions were created within both ventricular chambers of each animal through a catheter tip that could be cooled with a saline perfusate. Assignment of cooled versus noncooled RF delivery to either ventricle was alternated from one animal to the next. In each set of experiments, lesion volumes relative to the mode of RF delivery were compared. The mean power delivered via the cooled electrode (22.04 +/- 4.51 W) was significantly higher than that delivered via the noncooled electrode (6.10 +/- 2.47 W; P < 0.001). The mean duration of RF delivery was 42.7 +/- 11.2 sec for noncooled lesions versus 49.2 +/- 6.8 sec for cooled lesions (P < 0.01). Mean lesion volume was 436.07 +/- 177.00 mm3 for noncooled RF delivery versus 1247.78 +/- 520.51 mm3 for cooled RF delivery (P < 0.001). This significantly larger lesion size with cooled RF delivery was associated with no instance of impedance rise in 27 attempts versus 11 impedance rises in 28 attempts with noncooled RF (P < 0.001). CONCLUSIONS: Delivery of RF energy through a cooled catheter tip allows the creation of larger endomyocardial lesions by limiting the occurrence of impedance rise despite the delivery of greater energy. These observations suggest that, under certain conditions, resistive tissue heating at a distance from the site of current delivery may play an important role in RF ablation therapy.

Sotalol.

Sotalol causes noncardioselective beta-adrenergic antagonism and prolongation of repolarization of cardiac tissues (Class III electrophysiologic action). This dual pharmacologic profile confers unprecedented antiarrhythmic properties to the drug. Sotalol is highly bioavailable when administered orally in the fasting state and is mostly cleared unchanged in the urine with an apparent half-life of elimination of 15 to 17 hours. It has been found effective in the suppression of nearly all cardiac arrhythmias, with the exception of those precipitated by prolongation of ventricular repolarization. Its safety and efficacy relative to other antiarrhythmic drugs need to be examined more fully in randomized controlled trials of unselected patients. The adverse effects potentially associated with the use of sotalol are those commonly observed with beta-adrenergic blockade, as well as those resulting from excessive prolongation of the QT interval. The occurrence of torsade de pointes during treatment with sotalol may be minimized by limiting doses to no more than 640 mg/day and by strictly avoiding the development of hypokalemia.

Termination of ventricular tachycardia by nonpropagated local depolarization: further observations on entrainment of ventricular tachycardia from an area of slow conduction.

A 60-year-old woman with a large left ventricular apical aneurysm underwent preoperative catheter mapping of ventricular tachycardia. A zone of slow conduction with marked decremental conductive properties was identified between the left ventricular aneurysmal pouch and the right ventricular septum. Pacing from the right ventricular septum produced a QRS on the surface electrocardiogram of the same morphology as that of spontaneous ventricular tachycardia, while pacing from the left ventricular aneurysm caused tachycardia entrainment without fusion. Termination of ventricular tachycardia invariably occurred in association with an unpropagated left ventricular capture, followed by a change in ventricular activation to an opposite direction. This case provides a direct demonstration of reentrant ventricular tachycardia termination by orthodromic block in a zone of slow conduction.

Treatment of life-threatening ventricular arrhythmias with nonguided surgery supported by electrophysiologic testing and drug therapy.

Forty-six patients who had coronary artery disease, left ventricular aneurysm and life-threatening ventricular tachyarrhythmia underwent surgical treatment to eliminate or facilitate control of the arrhythmia. Surgery was performed without the assistance of intraoperative mapping techniques. Forty-three patients underwent preoperative or postoperative electrophysiologic testing, or both, and antiarrhythmic therapy was added, when indicated, postoperatively. The patients had a mean age of 63 years, a mean preoperative left ventricular ejection fraction of 27 +/- 9% and a mean preoperative left ventricular end-diastolic pressure of 23 +/- 9 mm Hg. Twenty-one patients (46%) underwent surgical treatment within 2 months of their last myocardial infarction. The overall operative mortality rate was 6.5% (three patients). Eighteen of the 43 operative survivors were discharged from the hospital on no antiarrhythmic therapy, whereas 25 received additional antiarrhythmic treatment. During a mean follow-up period of 36 months (range 2 to 88), there were 13 deaths; eight patients died suddenly, three died of congestive heart failure, one of myocardial reinfarction and one from a noncardiac cause. The overall cumulative cardiac mortality rate at 1, 2 and 3 years was 16, 22 and 35%, respectively, whereas the sudden cardiac death rate was 5, 12 and 20%, respectively. This experience suggests that high risk patients who undergo nonguided surgery for life-threatening ventricular arrhythmia and left ventricular aneurysm have a relatively low surgical mortality and a better long-term survival than previously reported. However, if utilized, such an approach must be systematically supported by perioperative electrophysiologic testing to determine the need for supplemental antiarrhythmic therapy.

Flecainide acetate for treatment of bypass tract mediated reentrant tachycardia.

Flecainide acetate was administered to 19 patients who had inducible sustained orthodromic atrioventricular reentrant tachycardia. Eleven of 18 patients had no inducible tachycardia and 7 patients continued to have inducible tachycardia while receiving flecainide. The effects of flecainide could not be evaluated because of hypotension during intravenous infusion in 1 patient. The main effect of the drug was a selective depression of retrograde conduction over the bypass tract, resulting in abolition of reentry or prolongation of tachycardia cycle length. The electrophysiologic effects of intravenous flecainide were concordant with those of oral flecainide in 5 patients who were studied during both regimens. Fifteen patients were discharged from the hospital on a regimen of flecainide. One patient received concomitant beta-blocking therapy. During an average follow-up of 18.5 months (range 2 to 48), 9 patients remained symptom free. Recurrences were observed in 5 patients, 3 of whom still had inducible tachycardia during electrophysiologic testing. Treatment had to be discontinued in 1 patient because of drug intolerance. Thus, flecainide is likely to be effective and well tolerated in the long-term treatment of at least 50% of patients who present with bypass tract mediated orthodromic reentrant tachycardia.

Treatment of atrial tachyarrhythmias and preexcitation syndrome with flecainide acetate.

Sixteen consecutive patients who had ventricular preexcitation complicated by atrial fibrillation or flutter were treated with intravenous flecainide acetate after treatment with as many as 5 unsuccessful trial regimens with other drugs. In 15 patients who had atrial fibrillation, the shortest RR interval during spontaneous episodes was 210 +/- 39 ms (mean +/- standard deviation), and the average ventricular rate was 208 +/- 37 beats/min. Intravenous flecainide prevented induction of atrial fibrillation in 4 of 9 patients and eliminated anterograde accessory pathway conduction in 9 of the 16 patients. In 5 patients whose atrial fibrillation remained inducible and who continued to have preexcitation, the shortest preexcited RR interval increased from 185 +/- 29 to 281 +/- 46 ms (p less than 0.01). Fourteen patients who had favorable responses to intravenous flecainide were given an oral regimen of the drug. Oral treatment was discontinued early because of proarrhythmic effects in 2 patients, and after 2 1/2 months because of headaches in 1 patient. Eleven patients, 5 receiving concomitant beta-blockade therapy, have continued to receive a regimen of flecainide for a mean of 21 months (range 3 to 48). Seven patients have had no clinical recurrence of arrhythmias. Recurrences in 4 patients have been rare and brief with no changes in therapy required.

Paroxysmal nonreentrant supraventricular tachycardia due to simultaneous fast and slow pathway conduction in dual atrioventricular node pathways.

Electrophysiologic studies were performed on a 49 year old woman who had paroxysmal nonreentrant supraventricular tachycardia due to simultaneous anterograde conduction through dual atrioventricular (AV) node pathways. Slow pathway conduction was inversely related to the preceding sinus cycle length and fast pathway conduction was determined by the Hs-A interval (measured from the His potential due to slow pathway conduction to the onset of the subsequent atrial electrogram). Major determinants of sustained simultaneous anterograde fast and slow pathway conduction during sinus rhythm were 1) a retrograde unidirectional block in both fast and slow pathways, and 2) a critical conduction delay in the slow pathway and a long enough Hs-A interval to allow sequential conduction of impulse from both pathways. Flecainide was successful in preventing recurrences of the tachycardia by eliminating slow pathway conduction during long-term follow-up.

Flecainide in the treatment of nonsustained ventricular tachycardia.

Thirty-two patients received flecainide acetate for nonsustained ventricular tachycardia after having had unsuccessful treatment with a mean of four antiarrhythmic drugs. The mean left ventricular ejection fraction was 41% in 27. Thirty-one patients had organic heart disease, and 22 patients had arrhythmia-related symptoms. Total suppression of ventricular tachycardia occurred in 22 patients. Thirty patients were discharged from the hospital receiving flecainide at a mean (+/- SD) dosage of 315 +/- 76 mg/d and 26 of these patients attained a mean trough plasma drug level of 567 +/- 254 ng/mL. One patient had proarrhythmia and 3 had worsening of heart failure. Twenty-two patients remained in the trial for a mean follow-up of 13 +/- 7 months. Five patients died (1 suddenly) during the follow-up period. Our data indicate that flecainide suppresses refractory nonsustained ventricular tachycardia in 69% of patients who have organic heart disease. Serious adverse effects were minimized by initiation of treatment in the hospital and careful surveillance of electrocardiograms and plasma drug levels.

Treatment of paroxysmal reentrant supraventricular tachycardia with flecainide acetate.

The electrophysiologic effects and therapeutic efficacy of intravenous and oral flecainide were studied in 15 patients with spontaneous and inducible sustained paroxysmal supraventricular tachycardia (SVT). Twelve patients had atrioventricular (AV) reentrance using an accessory pathway for retrograde conduction and 3 had AV nodal reentrance. Fourteen patients received intravenous flecainide (2 mg/kg body weight over 15 minutes) during an initial electrophysiologic study. Nine patients were restudied during oral flecainide administration (200 to 400 mg/day). After intravenous or oral flecainide therapy, reentrant SVT was noninducible in 6 patients with AV reentrance and in the 3 with AV nodal reentrance. In these 9 patients, intravenous flecainide prevented induction of reentrant SVT by depressing conduction over the retrograde limb of the reentry circuits. In the 6 patients with inducible sustained AV reentrant SVT before and after flecainide therapy, the cycle length of tachycardia increased significantly, mainly as the result of an increase in ventriculoatrial conduction time. There was concordance between the intravenous and the oral effects of flecainide on the mechanism of the SVT. Twelve patients continued oral flecainide treatment for a mean of 16 months (range 5 to 28). Tachycardia recurred in 3 of 4 patients whose arrhythmia remained inducible after flecainide therapy and in 1 of 8 patients whose SVT was suppressed. It is concluded that flecainide is an effective and convenient antiarrhythmic agent to treat patients who have AV nodal or AV reentrant SVT.

Flecainide and amiodarone interaction.

Oral amiodarone therapy was given to seven patients already taking oral flecainide regularly. In one additional patient, administration of flecainide was temporarily discontinued when amiodarone therapy was begun, and then resumed. Amiodarone produced a rise in mean dose-adjusted flecainide plasma level (trough plasma level at steady state/daily dose) from 2.3 +/- 0.8 to 3.4 +/- 0.9 (ng/ml)(mg/day) (p less than 0.01). Accordingly, the mean dose of flecainide required to maintain similar plasma levels of the drug was one-third lower during combined treatment than during therapy with flecainide alone. This drug interaction must be accounted for when amiodarone and flecainide are used concomitantly.

Combined bipolar dual chamber pacing and automatic implantable cardioverter/defibrillator.

A 67 year old man with recurrent hypotensive ventricular tachycardia, amiodarone-induced bradyarrhythmias and severe cardiac dysfunction underwent simultaneous implantation of an automatic cardioverter/defibrillator and bipolar atrioventricular (AV) pacemaker. The pacing electrodes were placed epicardially near the right atrial appendage and on the lateral right ventricular wall. The rate detector of the automatic defibrillator was placed epicardially on the posterobasal left ventricular wall. Effective bipolar AV pacing produced no false counting of the heart rate by the automatic cardioverter/defibrillator, and ventricular tachycardia properly inhibited the pacemaker. Long-term follow-up study confirmed the safety of this treatment. With proper precautions, bipolar AV pacing can be safely combined with an automatic cardioverter/defibrillator.

Adrenergically mediated variations in the energy required to defibrillate the heart: observations in closed-chest, nonanesthetized dogs.

The day-to-day variations in epicardial defibrillation threshold (DFT) were examined in closed-chest, unanesthetized dogs. In 11 animals, DFT decreased from 15.8 +/- 2.1 J (mean +/- SE) at the beginning of the study (day 1), to 7.4 +/- 1.7 J on day 2 (p less than .0001). DFT measured daily for 5 consecutive days in seven dogs decreased from 22.1 +/- 3.1 J on day 1 to 9.3 +/- 2.3 J on day 2 (p less than .01) and remained stable from day 2 to day 5. Transcardiac impedance, measured in six dogs, decreased from 112 +/- 6 omega on day 1 to 100 +/- 6 omega on day 2 (p = NS). Propranolol given on day 2 in 14 dogs increased DFT from 12.0 +/- 2.2 to 18.0 +/- 3.1 J (p less than .05). The effects on DFT of sequential administration of isoproterenol and propranolol were examined in 10 dogs. Isoproterenol decreased DFT from 10.0 +/- 1.9 to 5.5 +/- 1.5 J when given before propranolol (p less than .001, n = 10), and from 11.7 +/- 3.0 to 9.7 +/- 3.1 J when given after propranolol (p less than .05, n = 9). Propranolol increased DFT from 10.6 +/- 3.0 to 14.6 +/- 3.9 J when given before isoproterenol (p less than .02, n = 9), and from 10.7 +/- 1.4 to 14.4 +/- 1.5 J when given after isoproterenol (p less than .01, n = 10). These experiments demonstrate a sustained cardiac effect of epicardial defibrillation reflected by a decrease in DFT that is partially reversible by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)