Biomedical subjects
Publications and source records attributed to G V Naccarelli.
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Ibutilide fumarate is a new class III intravenous antiarrhythmic agent indicated for the acute termination of atrial fibrillation and flutter. Ibutilide prolongs repolarization in the atria and ventricle by enhancing the inward depolarizing, slow sodium current, a unique mechanism of action for a class III agent. Atrial refractoriness is prolonged with no evidence of reverse use dependence. Ibutilide may also block the delayed rectifier current, but this does not appear to be clinically relevant. In vitro and at high doses, ibutilide may shorten action potential duration, although this effect has not been noted clinically. Ibutilide can cause torsades de pointes in a rabbit model of proarrhythmia dependent on the formation of early afterdepolarizations. However, it causes less proarrhythmia than sotalol, dofetilide, or sematilide in this model. The pharmacokinetics of ibutilide are linear, its extravascular distribution is rapid and extensive, while its systemic clearance is high (elimination half-life 3-6 hours). Eight metabolites are formed by the liver, only one of which is slightly active. QT prolongation is dose dependent, is maximal at the end of the infusion, and returns to baseline within 2-4 hours following infusion. The pharmacokinetic and electrophysiologic characteristics of ibutilide are complementary in that any risk of proarrhythmia is made manageable by a short half-life. Almost all reported cases of drug-induced torsades de pointes ventricular tachycardia associated with ibutilide have occurred within 40 minutes of starting the infusion. Nevertheless, clinicians using ibutilide can further reduce the chance of torsades de pointes by being very familiar with the criteria for patient selection, and by being prepared to treat it should it occur. When used with full knowledge of its potential risks, ibutilide is a very effective intravenous agent for the acute termination of atrial fibrillation and flutter and is likely to become a significant treatment option for these arrhythmias.
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In order to compare the efficacy and long-term tolerability of flecainide acetate versus quinidine, 239 patients with paroxysmal atrial fibrillation were prospectively treated with flecainide (n = 122) or quinidine (n = 117) in an open-label, randomized trial. All patients were followed for 1 year after initiation of therapy unless their antiarrhythmic drug was discontinued due to an inadequate therapeutic response or intolerable side effects. Although both drugs were equally effective in adequately controlling recurrences of atrial fibrillation (difference, p = 0.282; not significant), fewer flecainide patients had to have their therapy discontinued due to adverse experiences (p = 0.012). Based on both endpoints (efficacy and tolerability), an estimated 70.5% of flecainide versus 55.4% of quinidine patients would remain effectively treated at the end of 1 year on therapy (p < or = 0.007). The findings of this prospective study suggest that in the treatment of paroxysmal atrial fibrillation (1) flecainide and quinidine are equally effective in the acceptable suppression of symptomatic paroxysmal atrial fibrillation; (2) flecainide is better tolerated than quinidine and is less likely to be discontinued due to adverse effects; and (3) given the overall endpoint of efficacy and tolerability, more patients are likely to continue long-term therapy with flecainide than with quinidine.
Reentrant paroxysmal supraventricular tachycardia (PSVT) are frequently encountered in clinical practice. Verapamil and flecainide have both been successfully used as chronic oral therapy to prevent PSVT recurrences. This open-label, randomized, multicenter study was designed to compare the efficacy and adverse effects of verapamil (median dose, 240 mg/day) versus flecainide (median dose, 200 mg/day) in patients with frequent and symptomatic attacks of PSVT (other than atrial fibrillation or flutter). A total of 121 patients receiving flecainide (n = 63) or verapamil (n = 58) were followed for 8.1 +/- 5.1 and 7.5 +/- 5.4 months, respectively. Response was judged clinically as effective or not by the treating physician. By life table analysis, 11% discontinued flecainide and 19% discontinued verapamil for inefficacy at 1 year (difference not significant). Both groups showed a marked reduction in the frequency of attacks of PSVT. Before therapy, 71% of flecainide patients and 73% of verapamil patients had > or = 2 attacks per month. During therapy, 86% of all flecainide patient-months and 73% of all verapamil patient-months occurred with 0 or 1 attack; 19 (30%) patients on flecainide completed the trial ( > 270 days) without symptomatic attacks versus 7 (13%) of the patients on verapamil (p = 0.026). Both drugs were well tolerated; 19% of the flecainide group discontinued primarily because of adverse effects, compared with 24% discontinuing verapamil for this reason (difference not significant). Both flecainide and verapamil are effective and well tolerated for the prevention of recurrences of PSVT. For patients in whom radiofrequency ablation procedures cannot be performed or are not indicated, either therapy is a reasonable choice for long-term prophylaxis.
OBJECTIVES: The effects of propafenone, a predominantly class IC antiarrhythmic drug, on defibrillation and pacing thresholds were evaluated in patients undergoing cardioverter-defibrillator implantation. BACKGROUND: Previous studies have shown that the class IC agents encainide and flecainide may increase the energy requirements for pacing and defibrillation. Animal studies with propafenone have shown inconsistent results regarding its effect on defibrillation energy requirements. This report investigated the effects of propafenone on defibrillation and pacing thresholds in humans. METHODS: After cardioverter-defibrillator implantation, 47 patients were enrolled in a double-blind, three-way parallel, randomized trial of 450 mg/day (Group 1) or 675 mg/day (Group 2) of oral propafenone or placebo (Group 3) for 3 to 7 days. Predischarge defibrillation and pacing thresholds after treatment were compared with baseline thresholds obtained at implantation. RESULTS: There was no statistically significant difference between implantation and predischarge defibrillation thresholds in the three groups (Group 1: [mean +/- SE] 11.0 +/- 1.3 vs. 12.1 +/- 1.5 J; Group 2: 11.5 +/- 1.1 vs. 13.6 +/- 1.3 J; Group 3: 12.5 +/- 1.2 vs. 13.3 +/- 1.6 J), and no significant difference between treatment groups was found with a 0.86 power to detect a 5-J difference between groups. Paired pulse width pacing thresholds at 2.8 V were compared in 14 patients. A small increase of 0.02 ms was noted at predischarge testing in patients treated with propafenone and placebo. CONCLUSIONS: Short-term oral propafenone (450 and 675 mg/day) does not significantly affect defibrillation or pacing thresholds. Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function.
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Radiofrequency catheter ablation has evolved into a front-line curative therapy for patients who have paroxysmal supraventricular tachycardia secondary to Wolff-Parkinson-White syndrome. AV nodal reentrant tachycardia, and atrial tachycardia. In patients with accessory pathways, cure rates exceed 90% in almost all anatomic locations. Equally high success rates are noted in patients with atriofascicular pathways and the permanent form of junctional reciprocating tachycardia. Complications secondary to catheter ablation of accessory pathways occur in 1% to 3% of patients and include cardiac perforation, tamponade, AV block, and stroke. In patients with AV modal reentrant tachycardia, selective slow pathway ablation is curative in over 95% of patients with a very low risk of AV block. Atrial tachycardias originating in both the left and right atria can be successfully ablated in over 80% of patients. Given the overall effectiveness of this procedure, radiofrequency catheter ablation should be considered as front-line therapy in patients with recurrent or drug-refractory paroxysmal supraventricular tachycardia. Although an effective therapy, the risks and benefits of this procedure need to be assessed in all patients who are candidates for this procedure.
NASPE proposes and supports the concept of a two-tracked training system in cardiac pacing. Track I training will properly train physicians for the prescription of pacemakers and the monitoring of pacemaker patients, and track II training will properly prepare physicians for the implantation of pacemakers. Regardless of specialty (cardiologist or surgeon) or training venue (cardiac pacing fellowship, cardiac electrophysiology and pacing fellowship, sabbatical or mentor sponsored training), it is recommended that these minimum standards be required for hospital credentialing. NASPE also supports the voluntary institution by training program directors of core pacing training in cardiovascular disease and cardiac electrophysiology fellowships. This core training does not in itself constitute proper track I or II training for physicians interested in adequately prescribing, monitoring, or implanting cardiac pacemakers.
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Sudden cardiac death usually occurs secondary to a ventricular tachyarrhythmia. Even under ideal circumstances only 20% of patients who have an out-of-hospital cardiac arrest survive to hospital discharge. Therefore, aggressive treatment and screening of high-risk patients are mandatory to improve survival rates. Risk stratification of high-risk patients, such as the post-myocardial infarction (MI) population, has been of limited value. Between 70% and 85% of "high-risk" post-MI patients, as defined by these screening tests, will not have a sustained ventricular tachyarrhythmia over several years of follow-up. The use of beta-blockers and possibly amiodarone may have some benefit in reducing mortality in high-risk patients after an MI. Several ongoing trials are studying the use of serial drug testing, amiodarone, and implantable cardioverter-defibrillators in reducing the incidence of sudden cardiac death in patients with potentially lethal ventricular arrhythmias. Although implantable cardioverter-defibrillators appear to be superior to antiarrhythmic drugs in reducing sudden cardiac death, total mortality may not be altered. In sustained ventricular tachyarrhythmias, sotalol and amiodarone appear to be superior to other drugs in preventing arrhythmia recurrence. Ongoing trials, such as the Antiarrhythmic Drug versus Implantable Device (AVID) trial may define the best strategy in these high-risk patients.
Adenosine has been used to diagnose latent preexcitation in patients with the Wolff-Parkinson-White syndrome. A case is reported in which intermittent preexcitation had been previously observed, however only retrograde accessory pathway conduction was documented at the time of invasive electrophysiological study. Administration of intravenous adenosine during sinus rhythm resulted in provocation of orthodromic atrioventricular reentry tachycardia.
Diltiazem has electrophysiologic effects similar to those of verapamil. Its efficacy and safety in 4 doses for treatment of induced supraventricular tachycardia (SVT) were examined and compared with those of placebo in 87 patients (25 with atrioventricular [AV] nodal reentry tachycardia, 60 with AV reentry associated with an accessory AV connection, and 2 with atrial tachycardia). Conversion to sinus rhythm occurred in 4 of 14 patients (29%) with 0.05 mg/kg of diltiazem, 16 of 19 (84%) with 0.15 mg/kg, 13 of 13 (100%) with 0.25 mg/kg, and 14 of 17 (82%) with 0.45 mg/kg compared with 6 of 24 (25%) treated with placebo. Conversion rates in groups receiving doses of 0.15 to 0.45 mg/kg of diltiazem were superior to that in the placebo group (p less than 0.001). Time to conversion was 3.0 +/- 2.6 minutes in responding diltiazem patients compared with 5.9 +/- 6.1 minutes in responding control patients. Diltiazem administration resulted in significant lengthening of SVT cycle length, AH interval, and AV nodal effective refractory period and block cycle length. The most frequent adverse response to diltiazem was hypotension (7 of 63 patients); however, only 4 patients had symptoms related to hypotension. Thus, intravenous diltiazem in doses of 0.15, 0.25 and 0.45 mg/kg is an effective and safe treatment for the acute management of SVT.
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