Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

BACKGROUND: INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. OBJECTIVES: This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. METHODS: Patients self-administered FlecIH over 8 minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. RESULTS: Mean age was 60.5 years, mean body mass index was 27.0 kg/m2, and 34.7% of the patients were women. All patients had ≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for ≤24 hours. The conversion rate was 42.6% (95% CI: 33.0%-52.6%) with a median time to conversion of 14.6 minutes. The conversion rate was 46.9% (95% CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. CONCLUSIONS: The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Comprehensive Intraprocedural Unfractionated Heparin Protocol During Catheter Ablation of Atrial Fibrillation in the Presence of Direct Oral Anticoagulants and Wide Spectrum of Body Mass Index.

INTRODUCTION: Data on optimal dosing of unfractionated heparin (UFH) in the presence of a direct oral anticoagulant (DOAC) to achieve and maintain an activated clotting time (ACT) of ≥300 seconds during catheter ablation of atrial fibrillation (CA-AF) are limited and prevalence of obesity adds to the unpredictable response to UFH. METHODS AND RESULTS: One hundred seventeen consecutive patients undergoing CA-AF were prospectively administered weight-adjusted, weight-based UFH using a pre-specified detailed protocol and retrospectively analyzed. Due to lack of distribution of UFH into muscle or adipose tissue and lower degree of vascularity in the latter compartment, each patient's ideal and actual weights were used to determine the adjusted-weight for use in all UFH doses. A UFH bolus of 200 units/kg was administered intravenously followed by an infusion of 35 units/kg/hour. The mean age was 65 years, and 85 patients (72.6%) were male. The average body mass index (BMI) was 30 (range 18-50) kg/m2. After the initial UFH bolus dose, 99 patients (84.6%) achieved ACT ≥300 sec with a mean (± SD) of 380 ± 79 sec. The mean time to reach an ACT ≥300 in all patients was 14.6 ± 12.4 minutes. Among all measured ACT values, 423 (90.8%) were ≥300 seconds. These results were consistent within all BMI categories. There were no intraprocedural thrombotic or hemorrhagic complications. Two patients (1.7%) sustained groin vascular access site hematoma without subsequent intervention and 7 patients (6%) experienced minor oozing post-procedurally. CONCLUSIONS: Our comprehensive weight-adjusted, weight-based UFH protocol, during CA-AF in presence of a DOAC, rapidly achieved and maintained an effective ACT irrespective of BMI.

Arrhythmias in Severe Trazodone Overdose.

BACKGROUND Trazodone is widely used in the treatment of depression, anxiety, and insomnia. It is thought to have a safe cardiac profile due to the relative lack of anticholinergic effects. Publications about cardiac toxicities of trazodone are scant. CASE REPORT A 55-year-old woman presented with acute disorder of consciousness secondary to an intentional trazodone overdose. She was found to have seizure activity without cerebral edema. The initial electrocardiogram was unremarkable, with a normal QTc interval. She eventually developed QTc prolongation that evolved into ventricular tachycardia, and then into a transient right bundle-branch block, left anterior fascicular block, and variable degrees of atrioventricular nodal blocks at 12-24 h after ingestion. She then developed generalized tonic-clonic seizures, cardiogenic shock, and respiratory arrest. She was intubated and treated with antiepileptics, norepinephrine, and dopamine infusion. QTc interval prolongation gradually resolved and the various forms of heart block did not recur after at 24-36 h. She did not require transcutaneous pacing, and was successfully extubated with intact neurological function. CONCLUSIONS Fatal arrhythmias can occur in trazodone overdose. Close monitoring and supportive care are crucial for patient survival.

Honing in on optimal ventricular pacing sites: an argument for his bundle pacing.

OPINION STATEMENT: Frequent ventricular pacing is often or completely unavoidable in patients with high-grade or complete heart block. Over time, patients with high-burden RV pacing are at risk for developing symptomatic cardiomyopathy due to pacing-induced ventricular dyssynchrony. Growing awareness of this concern has generated interest in alternative pacing sites like the septum and outflow tract, the thinking being that these sites will more closely mimic His-Purkinje-mediated ventricular activation. Numerous studies have met with mixed results likely due to the fact that-to quote Marvin Gaye-there ain't nothing like the real thing. Herein lies the advantage of His bundle pacing (HBP), as it is the only pacing modality capable of physiological ventricular activation. HBP has been demonstrated to be safe and reliable in various forms of AV block with minimal drawbacks, namely modestly higher pacing thresholds when compared with other RV sites. Additionally, HBP is a truly physiologic alternative to biventricular pacing to effect cardiac resynchronization therapy (CRT), a concept supported by small observational and prospective studies. In our view, His bundle pacing should be considered in nearly all patients requiring ventricular pacing.