Samir Fareh

Bio: Samir Fareh is an academic researcher from Montreal Heart Institute. The author has contributed to research in topics: Atrial tachycardia & Atrial fibrillation. The author has an hindex of 7, co-authored 7 publications receiving 1988 citations. Previous affiliations of Samir Fareh include McGill University.

Promotion of atrial fibrillation by heart failure in dogs: atrial remodeling of a different sort.

Abstract: Background—Studies of atrial fibrillation (AF) due to atrial tachycardia have provided insights into the remodeling mechanisms by which “AF begets AF” but have not elucidated the substrate that initially supports AF before remodeling occurs. We studied the effects of congestive heart failure (CHF), an entity strongly associated with clinical AF, on atrial electrophysiology in the dog and compared the results with those in dogs subjected to rapid atrial pacing (RAP; 400 bpm) with a controlled ventricular rate (AV block plus ventricular pacemaker at 80 bpm). Methods and Results—CHF induced by 5 weeks of rapid ventricular pacing (220 to 240 bpm) increased the duration of AF induced by burst pacing (from 8±4 seconds in control dogs to 535±82 seconds; P<0.01), similar to the effect of 1 week of RAP (713±300 seconds). In contrast to RAP, CHF did not alter atrial refractory period, refractoriness heterogeneity, or conduction velocity at a cycle length of 360 ms; however, CHF dogs had a substantial increase in th...

Importance of Refractoriness Heterogeneity in the Enhanced Vulnerability to Atrial Fibrillation Induction Caused by Tachycardia-Induced Atrial Electrical Remodeling

Abstract: Background—Rapid atrial activation causes electrical remodeling that promotes the occurrence and the maintenance of atrial fibrillation (AF). Although remodeling has been shown to alter electrophysiological variables, the spatial uniformity of these changes is unknown. Methods and Results—Dogs subjected to rapid atrial pacing (400 bpm) for 24 hours (n=12) were compared with sham-operated dogs (instrumented but not paced, n=12). Epicardial mapping (240 bipolar electrodes) and extrastimulation at a large number of sites (mean±SEM, 66±4 per dog) were used to evaluate atrial activation and the heterogeneity of the effective refractory period (ERP), respectively. Rapid pacing increased both the percentage of sites at which AF could be induced by single premature stimuli (from 2.6±0.9% to 11.8±2.8%, P=0.007) and AF duration (from 39±28 to 146±49 seconds, P=0.03). Atrial tachycardia decreased atrial ERP (from 120±4 to 103±2 ms, P=0.003), increased the coefficient of variation of ERP (from 14.9±0.9% to 20.7±0.9%,...

The T-type Ca(2+) channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs.

Abstract: Background —Ca2+ overload is believed to play a role in tachycardia-induced atrial electrophysiological remodeling. L-type Ca2+ channel blockers attenuate effective refractory period (ERP) changes caused by 24 hours of atrial tachycardia but may not substantially alter atrial fibrillation (AF) inducibility. This study assessed the effects of the T-type Ca2+ channel blocker mibefradil on tachycardia-induced atrial remodeling. Methods and Results —Dogs subjected to rapid atrial pacing (400 bpm) for 7 days were treated with mibefradil (100 mg/d, n=8) or matching placebo (n=10) in blinded fashion. Radiofrequency ablation of atrioventricular conduction and ventricular pacing were used to control ventricular rate. Placebo dogs showed significant decreases in atrial ERP (76±5 ms at a cycle length of 300 ms) and increases in ERP heterogeneity (27.7±2.4%), AF duration (414±232 seconds), and AF inducibility by single extrastimuli (41±10% of sites) compared with 10 unpaced control dogs (ERP 114±3 ms, ERP heterogeneity 13.8±0.9%, AF duration 7±3 seconds, AF inducibility 1.9±1.0% of sites). The changes caused by atrial tachycardia were strongly attenuated in mibefradil dogs, with ERPs averaging 102±7 ms, ERP heterogeneity 18.8±1.4%, AF duration 3±1 seconds, and AF inducibility 9.6±4.0% of sites. Among mibefradil-treated dogs, ERP, AF duration, and inducibility correlated with plasma drug concentration. Acute mibefradil administration did not alter ERP or AF. Conclusions —Mibefradil, a drug with strong T-type Ca2+ channel blocking properties, prevents AF-promoting electrophysiological remodeling by atrial tachycardia. These findings have important potential implications for the mechanisms of tachycardia-induced atrial remodeling and demonstrate the feasibility of preventing electrical remodeling caused by several days of atrial tachycardia.

Differential efficacy of L- and T-type calcium channel blockers in preventing tachycardia-induced atrial remodeling in dogs.

Abstract: Background: Tachycardia-induced remodeling likely plays an important role in atrial fibrillation (AF) maintenance and recurrence after cardioversion, and Ca2+ overload may be an important mediator. This study was designed to evaluate the relative efficacies of selective T-type (mibefradil) and L-type (diltiazem) Ca2+-channel blockers in preventing tachycardia-induced atrial remodeling. Methods: Dogs were given daily doses of mibefradil (100 mg), diltiazem (240 mg) or placebo in a blinded fashion, beginning 4 days before and continuing through a 7-day period of atrial pacing at 400 bpm. An electrophysiological study was then performed to assess changes in refractoriness, refractoriness heterogeneity and AF duration. Results: Mean duration of burst-pacing induced AF was similar in placebo (567±203 s) and diltiazem-treated (963±280 s, P = NS) animals, but was much less in mibefradil-treated dogs (3.6±0.9 s, P <0.002) and non-paced controls (6.6±2.7 s). In contrast to mibefradil, diltiazem did not alter tachycardia-induced refractoriness abbreviation or heterogeneity. To exclude inadequate dosing as an explanation for diltiazem's inefficacy, we studied an additional group of dogs treated with 720 mg/day of diltiazem, and again noted no protective effect. Acute intravenous administration of diltiazem to control dogs failed to alter atrial refractoriness or AF duration, excluding a masking of remodeling suppression by offsetting profibrillatory effects of the drug. Conclusions: Whereas the selective T-type Ca2+-channel blocker mibefradil protects against atrial remodeling caused by 7-day atrial tachycardia, the selective L-type blocker diltiazem is without effect. These findings are potentially important for understanding the mechanisms and prevention of clinically-relevant atrial-tachycardia-induced remodeling.

Dihydropyridine and beta adrenergic receptor binding in dogs with tachycardia-induced atrial fibrillation.

Abstract: Background: We have shown that rapid atrial activation, as occurs during atrial fibrillation (AF), reduces L-type Ca2+ current ( I Ca) and that this is the principal mechanism of the action potential duration and refractoriness changes that characterize tachycardia-induced atrial remodeling. The present study was designed to determine whether atrial tachycardia alters biochemical indices of the number of L-type Ca2+ channels and/or of the number and binding affinity of β-adrenergic receptors. Methods: In canine atrial sarcolemmal preparations, the number and binding affinity of dihydropyridine receptors were determined with the use of 3H-nitrendipine and that of β-adrenergic receptors with 125I-iodocyanopindolol. Results were obtained with preparations from dogs paced at 400/min for 1 (P1, n =20), 7 (P7, n =9), and 42 (P42, n =9) days, and compared with observations in sham-operated controls (P0, n =14). Results: Pacing reduced the B max of dihydropyridine receptors, from 157±18 fmol/mg (P0) to 116±9 fmol/mg (P1, P <0.05), 100±14 fmol/mg (P7, P <0.05) and 94±9 fmol/mg (P42, P <0 .01). The affinity of dihydropyridine receptors was unchanged, with the K d averaging 711±102 pM, 656±74 pM, 633±155 pM and 585±92 pM in P0, P1, P7 and P42 dogs. Neither B max nor K d of β-adrenergic receptors was altered by rapid pacing. Values of B max of dihydropyridine receptors correlated with atrial I Ca current density ( r 2=0.95) and ERP ( r 2=0.99). Conclusions: Rapid atrial activation results in downregulation in the number of dihydropyridine receptors without altering the number or affinity of β-adrenergic receptors. The reductions in I Ca that play an important role in the atrial electrical remodeling by which ‘AF begets AF’ appear to be due at least in part to a decrease in the number of L-type Ca2+ channels in cardiac cell membranes.

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society

Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect Nancy M. Albert, PhD, RN, FAHA Biykem Bozkurt, MD, PhD, FACC, FAHA Ralph G. Brindis, MD, MPH, MACC Mark A. Creager, MD, FACC, FAHA[#][1] Lesley H. Curtis, PhD, FAHA David DeMets, PhD[#][1] Robert A

ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society

Abstract: Sidney C. Smith, Jr, MD, FACC, FAHA, FESC, Chair; Alice K. Jacobs, MD, FACC, FAHA, Vice-Chair; Cynthia D. Adams, MSN, APRN-BC, FAHA; Jeffery L. Anderson, MD, FACC, FAHA; Elliott M. Antman, MD, FACC, FAHA[‡][1]; Jonathan L. Halperin, MD, FACC, FAHA; Sharon Ann Hunt, MD, FACC, FAHA; Rick Nishimura,

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary

Abstract: Preamble 2072 1. Introduction 2074 2. Clinical Characteristics and Evaluation of AF 2076 3. Thromboembolic Risk and Treatment 2077 4. Rate Control: Recommendations 2079 5. Rhythm Control: Recommendations 2080 6. Specific Patient Groups and AF: Recommendations 2086 7. Evidence Gaps and Future Research Directions 2089 References 2090 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) 2095 Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant) 2097 Appendix 3. Initial Clinical Evaluation in Patients With AF 2104 The medical profession should play a central role in evaluating the evidence related to drugs, devices, and procedures for the detection, management, and prevention of disease. When properly applied, expert analysis of available data on the benefits and risks of these therapies and procedures can improve the quality of care, optimize patient outcomes, and favorably affect costs by focusing resources on the most effective strategies. An organized …

Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study.

Abstract: Background— Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality. Methods and Results— We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increase...

ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology

Abstract: Atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, is increasing in prevalence as the population ages. Although it is often associated with heart disease, AF occurs in many patients with no detectable disease. Hemodynamic impairment and thromboembolic events result in significant morbidity, mortality, and cost. Accordingly, the American College of Cardiology (ACC), the American Heart Association (AHA), and the European Society of Cardiology (ESC) created a committee of experts to establish guidelines for management of this arrhythmia. The committee was composed of 8 members representing the ACC and AHA, 4 representing the ESC, 1 from the North American Society of Pacing and Electrophysiology (NASPE), and a representative of the Johns Hopkins University Evidence-Based Practice Center representing the Agency for Healthcare Research and Quality’s report on Atrial Fibrillation in the Elderly. This document was reviewed by 3 official reviewers nominated by the ACC, 3 nominated by the AHA, and 3 nominated by the ESC, as well as by the ACC Clinical Electrophysiology Committee, the AHA ECG and Arrhythmia Committee, NASPE, and 25 reviewers nominated by the writing committee. The document was approved for publication by the governing bodies of the ACC, AHA, and ESC and officially endorsed by NASPE. These guidelines will be reviewed annually by the task force and will be considered current unless the task force revises or withdraws them from distribution. The committee conducted a comprehensive review of the literature from 1980 to June 2000 relevant to AF using the following databases: PubMed/Medline, EMBASE, the Cochrane Library (including the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Registry), and Best Evidence. Searches were limited to English language sources and to human subjects. ### A. Atrial Fibrillation AF is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. On the electrocardiogram (ECG), AF …