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1.
J Cardiovasc Pharmacol ; 50(1): 35-40, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17666913

ABSTRACT

OBJECTIVES: To determine the acute effects of vernakalant (RSD1235) on electrophysiologic (EP) properties in humans. BACKGROUND: Vernakalant is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more "atrial-selective" than available agents. METHODS: Patients (N=19; 53% male; age, 48+/-11 years) underwent EP study before and after 25 minutes of intravenous vernakalant administration: 2 mg/kg over 10 min+0.5 mg/kg/hr for 35 min or 4 mg/kg over 10 min+1 mg/kg/hr for 35 min. EP measurements, including atrial refractory period (AERP) and ventricular refractory period (VERP), were obtained. RESULTS: The lower dose prolonged AERP at 600, but not at 400 or 300 msec paced cycle length. The higher dose significantly prolonged AERP from 203+/-31 msec to 228+/-24 msec at 600 msec, 182+/-30 msec to 207+/-27 msec at 400 msec, and 172 msec+/-24 to 193+/-21 msec at 300 msec. There was no significant prolongation of VERP at either dose or at any cycle length. There was a small but significant prolongation of AV nodal refractoriness; Wenckebach cycle length prolonged by 18+/-12 msec (from baseline 343+/-54 msec) at the higher dose (P<0.05). Sinus node recovery time also increased by 123+/-158 msec (from baseline 928+/-237 msec) at the higher dose (P<0.05). There was a slight prolongation of QRS duration at the higher dose, during ventricular pacing at CL=400 msec (15+/-15 msec, P=0.0547). QT and HV intervals were unchanged. CONCLUSIONS: At doses similar to those tested clinically, vernakalant dose-dependently prolonged atrial refractoriness, prolonged AV nodal conduction and refractoriness, and slightly prolonged QRS duration, but it had no effect on ventricular refractoriness.


Subject(s)
Anisoles/pharmacology , Anti-Arrhythmia Agents/pharmacology , Atrial Function/drug effects , Pyrrolidines/pharmacology , Refractory Period, Electrophysiological , Adult , Anisoles/administration & dosage , Anisoles/adverse effects , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/adverse effects , Atrioventricular Node/drug effects , Dose-Response Relationship, Drug , Electrocardiography , Electrophysiology , Female , Heart Rate/drug effects , Humans , Infusions, Intravenous , Male , Middle Aged , Pyrrolidines/administration & dosage , Pyrrolidines/adverse effects , Sinoatrial Node/drug effects , Ventricular Function/drug effects
2.
Can J Cardiol ; 22(5): 383-6, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16639472

ABSTRACT

BACKGROUND: The severity of symptoms caused by atrial fibrillation (AF) is extremely variable. Quantifying the effect of AF on patient well-being is important but there is no simple, commonly accepted measure of the effect of AF on quality of life (QoL). Current QoL measures are cumbersome and impractical for clinical use. OBJECTIVE: To create a simple, concise and readily usable AF severity score to facilitate treatment decisions and physician communication. METHODS: The Canadian Cardiovascular Society (CCS) Severity of Atrial Fibrillation (SAF) Scale is analogous to the CCS Angina Functional Class. The CCS-SAF score is determined using three steps: documentation of possible AF-related symptoms (palpitations, dyspnea, dizziness/syncope, chest pain, weakness/fatigue); determination of symptom-rhythm correlation; and assessment of the effect of these symptoms on patient daily function and QoL. CCS-SAF scores range from 0 (asymptomatic) to 4 (severe impact of symptoms on QoL and activities of daily living). Patients are also categorized by type of AF (paroxysmal versus persistent/permanent). The CCS-SAF Scale will be validated using accepted measures of patient-perceived severity of symptoms and impairment of QoL and will require 'field testing' to ensure its applicability and reproducibility in the clinical setting. CONCLUSIONS: This type of symptom severity scale, like the New York Heart Association Functional Class for heart failure symptoms and the CCS Functional Class for angina symptoms, trades precision and comprehensiveness for simplicity and ease of use at the bedside. A common language to quantify AF severity may help to improve patient care.


Subject(s)
Atrial Fibrillation/classification , Atrial Fibrillation/diagnosis , Cardiology/instrumentation , Point-of-Care Systems , Severity of Illness Index , Atrial Fibrillation/complications , Canada , Chest Pain/etiology , Dizziness/etiology , Dyspnea/etiology , Fatigue/etiology , Humans , Quality of Life , Societies, Medical
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