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Introduction: Little is known about very early atrial fibrillation (AF) ablation after first AF detection., Methods: We evaluated patients with AF ablation <4 months from newly diagnosed paroxysmal AF (NEWPaAF) and newly diagnosed persistent AF (NEWPeAF). We compared the two patient populations and compared ablation outcomes to those undergoing later ablation., Results: Ablation was done <4 months from AF diagnosis in 353 patients (135 = paroxysmal, 218 = persistent). Early ablation outcome was best for NEWPaAF versus NEWPeAF for initial (p = 0.030) but not final (p = 0.102) ablation. Despite recent AF diagnosis in both groups, they were clinically quite different. NEWPaAF patients were younger (64.3 ± 13.0 vs. 67.3 ± 10.9, p = 0.0020), failed fewer drugs (0.39 vs. 0.60, p = 0.007), had smaller LA size (4.12 ± 0.58 vs. 4.48 ± 0.59 cm, p < 0.0001), lower BMI (28.8 ± 5.0 vs. 30.3 ± 6.0, p = 0.016), and less CAD (3.7% vs. 11.5%, p = 0.007), cardiomyopathies (2.2% vs. 22.9%, p = 0.0001), hypertension (46.7% vs. 67.4%, p < 0.0001), diabetes (8.1% vs. 17.4%, p = 0.011) and sleep apnea (20.0% vs. 30.3%, p = 0.031). For NEWPaAF, early ablation AF-free outcome was no better than later ablation (p = 0.314). For NEWPeAF, AF-free outcomes were better for early ablation than later ablation (p < 0.0001). Delaying ablation allowed more strokes/TIAs in both AF types (paroxysmal p = 0.014, persistent p < 0.0001)., Conclusions: Patients presenting for early ablation after newly diagnosed persistent AF have more pre-existing comorbidities and worse initial ablation outcomes than patients with NEWPaAF. For NEWPaAF, there was no advantage to early ablation, as long as the AF remained paroxysmal. For NEWPeAF, early ablation gave better outcomes than later ablation and they should undergo early ablation. For both AF types, waiting was associated with more neurologic events, suggesting all patients should consider earlier ablation., (© 2024 Wiley Periodicals LLC.)

Background: Little is known about the very long term durability of atrial fibrillation (AF) ablation., Objective: The purpose of this study was to evaluate very long term AF ablation outcomes., Methods: We followed 5200 patients undergoing 7145 ablation procedures. We evaluated outcomes after single and multiple ablation procedures for paroxysmal (PAF; 33.6%), persistent (PeAF; 56.4%), and long-standing (LsAF; 9.9%) AF. We compared 3 ablation eras by initial ablation catheter: early (101 patients) using solid big tip (SBT) catheters (October 2003 to December 2005), intermediate (2143 patients) using open irrigated tip (OIT) catheters (December 2005 to August 2016), and contemporary (2956 patients) using contact force (CF) catheters (March 2014 to December 2021)., Results: AF freedom at 5, 10, and 15 years was as follows: initial ablation: PAF 67.8%, 56.3%, 47.6%; PeAF 46.6%, 35.6%, 26.5%; and LsAF 30.4%, 18.0%, 3.4%; final ablation: PAF 80.3%, 72.6%, 62.5%; PeAF 60.1%, 50.2%, 42.5%; and LsAF 43.4%, 32.0%, 20.6%. For PAF and PeAF, CF ablation procedures were better than OIT ablation procedures (P < .0001) and both were better than SBT ablation procedures (P < .001). LsAF had no outcome improvement over the eras. The 8-year success rate after final ablation for CF, OIT, and SBT catheter eras was as follows: PAF 79.1%, 71.8%, 60.0%; PeAF 55.9%, 50.7%, 38.0%; and LsAF 42.7%, 36.2%, 31.8%. Highest AF recurrence was in the first 2 years, with a 2- to 15-year recurrence of 2%/yr. Success predictors after initial and final ablation procedures were younger age, smaller left atrium, shorter AF duration, male sex, less persistent AF, lower CHA 2 DS 2 -VASc score, fewer drugs failed, and more recent catheter era., Conclusion: After year 2, there is 2%/yr recurrence rate for all AF types. Ablation success is best in the CF catheter era, intermediate in the OIT era, and worst in the SBT era. Over the ablation eras, outcomes improved for PAF and PeAF but not for LsAF. We should follow patients indefinitely after ablation. We need an understanding of how to better ablate more persistent AF., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Twenty-one patients with heart failure (New York Heart Association [NYHA] class II to IV) received a 24-hour infusion of enoximone followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I to III received an 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0, or 10.0 micrograms/kg/min. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/min without a loading dose. Serial assessment of hemodynamics, plasma levels of enoximone and enoximone sulfoxide, and ventricular ectopy were performed. Enoximone produced a clinically significant increase in cardiac index, and a decrease in mean pulmonary artery wedge pressure and systemic vascular resistance in all groups. Enoximone mildly increased heart rate, and had a minimal effect on mean arterial pressure. There was no statistically significant change in ventricular ectopy during the infusion. Significant hemodynamic improvement was noted at even the lowest infusion rate, and did not increase in linear fashion at higher infusion rates. In patients who did not receive an initial loading bolus of 0.5 mg/kg, the increase in cardiac index was delayed by approximately 1 hour. Plasma concentrations of both enoximone and its major metabolite continued to rise throughout the 24-hour infusion in group III (10.0 micrograms/kg/min), rather than reaching steady state as predicted by the terminal exponential half-lives of these compounds. This is suggestive of nonlinear pharmacokinetics and indicates a potential for excessive accumulation of enoximone and its metabolite during prolonged infusion. These findings may have important implications in guiding the intravenous administration of enoximone.(ABSTRACT TRUNCATED AT 250 WORDS)

Enoximone is a phosphodiesterase inhibitor, which has been studied extensively for use in the management of patients with moderate-to-severe heart failure. The authors have studied the absorption and disposition kinetics of enoximone and its primary metabolite, enoximone sulfoxide, after both single oral doses of enoximone and at steady-state after short-term chronic oral therapy. A total of ten patients (two female, eight male) with moderate-to-severe heart failure (NYHA class II-IV) were enrolled into the study after giving written informed consent. The plasma levels of enoximone sulfoxide were greater than those of enoximone at all sampling times. The peak enoximone sulfoxide plasma concentrations ranged from 3.5 to 17.3 times the peak enoximone plasma levels for individual patients. The average steady-state plasma concentrations for enoximone were 115 +/- 40 ng/mL and 190 +/- 78 ng/mL for 50 mg every 8 hours and 100 mg every 8 hours dosage regimens, respectively. The absorption and disposition kinetics of enoximone were found to be significantly variable between patients. The authors also evaluated the relationship between dose administered and steady-state plasma levels as well as the relationship between the observed and predicted steady-state plasma levels. The authors found a linear relationship between the dose that was administered and the accrued plasma levels, as well as a good correlation between the predicted and observed steady-state levels. Although these data confirm previous reports that the sulfide metabolite of enoximone accumulates extensively in the plasma during oral therapy, reaching levels much higher than those of enoximone, these data do not support previous suggestions that the disposition of enoximone is nonlinear.

"Purple toes" syndrome and a generalized skin eruption developed in a 73-year-old woman who was taking warfarin sodium (Coumadin) as well as antiarrhythmic agents after a stroke. Both the rash and the discoloration of her feet were apparently related to use of warfarin and gradually resolved after discontinuation of the drug.

Propafenone disposition kinetics were studied after intravenous and oral doses in patients with ventricular arrhythmias. Plasma concentration-time data were fit to a two-compartment model for all but one patient, whose data required fitting to a three-compartment model. The model-independent calculated values of clearance, steady-state volume of distribution, and terminal t1/2 were 11.2 +/- 4.8 ml/min/kg, 3.6 +/- 2.1 l/kg, and 5.0 +/- 3.6 hr. After 5 days on oral propafenone, elimination t1/2 was 6.2 +/- 3.3 hr. The longer t1/2s and the estimates of steady-state bioavailability above 100% suggests that clearance decreases during chronic oral dosing. Considerable intersubject variability was noted in all disposition parameters.

Sixteen patients with ventricular tachycardia (VT) or nonfatal cardiac arrest were treated with propafenone (P), 900 mg/day. Electrophysiologic studies were performed before and during therapy with P. All patients had inducible sustained VT at the baseline study. During P therapy, VT was not inducible in 1 patient, was unsustained in 1 and was harder to induce in 2 patients. P increased the cycle length of VT from 307 +/- 67 to 382 +/- 107 ms. Five patients began outpatient therapy with P, including 2 in whom VT was slowed to less than 125 beats/min. Two are arrhythmia-free during follow-up of 2 and 8 months. P significantly increased intraatrial conduction time (from 44 +/- 12 to 72 +/- 22 ms), AH interval (from 115 +/- 36 to 152 +/- 45 ms), HV interval (from 55 +/- 18 to 92 +/- 42 ms), QRS duration (from 140 +/- 36 to 180 +/- 48 ms) and QT interval (from 402 +/- 30 to 459 +/- 60 ms). P increased atrial (from 247 +/- 36 to 288 +/- 38 ms) and ventricular (from 249 +/- 20 to 277 +/- 32 ms) effective refractory periods, Sinus cycle length did not change, but the corrected sinus node recovery time increased (from 162 +/- 85 to 821 +/- 1,607 ms). P aggravated arrhythmias in 4 patients. The plasma P concentration, measured either at the time of electrophysiologic studies of when therapy was discontinued, was 753 +/- 428 ng/ml. P suppressed ventricular ectopic beats in 33% and increased them in 1 patient. P has antiarrhythmic activity against VT similar to that of other antiarrhythmic drugs and has potential for serious adverse effects in some patients.

Sixty-five patients with symptomatic, drug-refractory, sustained ventricular tachycardia or fibrillation were treated with oral sotalol (80 to 480 mg twice daily). Sotalol was withdrawn in 11 patients because of continued inducibility of ventricular tachycardia at the time of follow-up electrophysiologic study. Therefore, the clinical effectiveness of sotalol could be evaluated in 54 patients followed up for 11.5 +/- 6 months (range 0.2 to 25). The actuarial incidence of successful sotalol therapy was 54 +/- 13% at 6 months and 47 +/- 13% at 12 months. In 39 patients who underwent electrophysiologic testing while receiving oral sotalol, the drug prevented the reinduction of ventricular tachycardia/fibrillation in 8 (20%). During follow-up study, arrhythmia recurred in 1 (17%) of 6 patients whose ventricular tachycardia was noninducible with oral sotalol and in 8 (44%) of 18 with inducible tachycardia but who were continued on oral sotalol therapy. Adverse effects were noted in 28 patients (42%), requiring drug withdrawal in 13 (22%) and dose reduction after hospital discharge in 10 (15%). Exacerbation of ventricular arrhythmia occurred in six patients (9%), one of whom had associated hypokalemia. Sotalol is frequently useful in the control of intractable, life-threatening ventricular arrhythmias, and its efficacy appears to be predicted by programmed stimulation. However, there is a high rate of limiting side effects, which precludes its use in a large number of patients, and a substantial risk of arrhythmia exacerbation.

The chemical and pharmacologic properties, pharmacokinetics, drug interactions, clinical efficacy, adverse effects, and dosage of propafenone are reviewed. Propafenone is a class IC antiarrhythmic agent that is structurally similar to the beta blockers but that has only weak beta-blocking and calcium-channel-blocking activity. It is well absorbed after oral administration, but systemic bioavailability is only 12% after a 300-mg dose. Among extensive metabolizers (greater than 90% of the United States population), bioavailability seems to vary nonlinearly with dose and increases substantially with food; these effects are not seen in poor metabolizers. Elimination is primarily hepatic, with a mean elimination half-life after oral administration of 5.5 hours in extensive metabolizers and 17.2 hours in poor metabolizers. The relationship between plasma propafenone concentration and clinical response varies considerably among individual patients; therefore, plasma concentrations have limited usefulness in predicting efficacy or electrophysiologic effects. Propafenone is effective in treating ventricular tachycardia and in suppressing premature ventricular complexes (PVCs). It is less effective in the treatment of refractory ventricular tachycardia. Concurrent administration of digoxin, warfarin, or metoprolol with propafenone has been shown to increase the serum concentrations of those three drugs, while cimetidine slightly increases the propafenone concentrations. Additive pharmacologic effect can occur when lidocaine, procainamide, and quinidine are combined with propafenone. Overall, 21% to 32% of patients experience adverse effects, with 3% to 7% of these serious enough to warrant discontinuing therapy. The most common adverse effects are dizziness or lightheadedness, metallic taste, and nausea and vomiting; the most serious adverse effects are proarrhythmic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirteen patients with drug-resistant, life-threatening ventricular arrhythmias and inducible sustained ventricular tachycardia (VT) at electrophysiologic study received moricizine HC1 (ethmozine), 10 mg/kg/day orally. Eight patients underwent electrophysiologic study before and after drug administration; the arrhythmia became noninducible in one. In five other patients, spontaneous sustained VT occurred after 1 to 5 days of drug therapy, and one patient had a worsening of arrhythmias on ethmozine. Ethmozine prolonged infranodal conduction time (HV interval) (51.4 +/- 13.8 msec to 69.3 +/- 17.7 msec [mean +/- SD]), PR interval (201 +/- 28.1 msec to 244 +/- 62.2 msec), and QRS interval (123 +/- 27 msec to 147 +/- 32 msec). Ventricular refractory periods were not consistently affected, and only the one patient who became noninducible had an increase in effective ventricular refractory period (280 to 310 msec). The drug had no significant effect on sinus cycle length or sinus node recovery time, atrial conduction or refractoriness, or atrioventricular nodal refractoriness. Ethmozine had no effect on radionuclide ejection fraction (25.5 +/- 12.7% to 28.2 +/- 13.8%) or cardiac index (2.4 +/- 0.7 to 3.0 +/- 0.6 ml/min/m2) and caused no significant changes in mean aortic, right atrial, pulmonary arterial, or pulmonary capillary wedge pressures. Although the drug is well tolerated and produces no untoward hemodynamic effects, ethmozine is relatively ineffective in patients with sustained VT refractory to conventional antiarrhythmic agents.