Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs
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Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs. / Ornelas-Loredo, Aylin; Kany, Shinwan; Abraham, Vihas; Alzahrani, Zain; Darbar, Faisal A; Sridhar, Arvind; Ahmed, Maha; Alamar, Ihab; Menon, Ambili; Zhang, Meihang; Chen, Yining; Hong, Liang; Konda, Sreenivas; Darbar, Dawood.
in: JAMA CARDIOL, Jahrgang 5, Nr. 1, 01.01.2020, S. 57-64.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Association Between Obesity-Mediated Atrial Fibrillation and Therapy With Sodium Channel Blocker Antiarrhythmic Drugs
AU - Ornelas-Loredo, Aylin
AU - Kany, Shinwan
AU - Abraham, Vihas
AU - Alzahrani, Zain
AU - Darbar, Faisal A
AU - Sridhar, Arvind
AU - Ahmed, Maha
AU - Alamar, Ihab
AU - Menon, Ambili
AU - Zhang, Meihang
AU - Chen, Yining
AU - Hong, Liang
AU - Konda, Sreenivas
AU - Darbar, Dawood
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Importance: The association between obesity, an established risk factor for atrial fibrillation (AF), and response to antiarrhythmic drugs (AADs) remains unclear.Objective: To test the hypothesis that obesity differentially mediates response to AADs in patients with symptomatic AF and in mice with diet-induced obesity (DIO) and pacing induced AF.Design, Setting, and Participants: An observational cohort study was conducted including 311 patients enrolled in a clinical-genetic registry. Mice fed a high-fat diet for 10 weeks were also evaluated. The study was conducted from January 1, 2018, to June 2, 2019.Main Outcomes and Measures: Symptomatic response was defined as continuation of the same AAD for at least 3 months. Nonresponse was defined as discontinuation of the AAD within 3 months of initiation because of poor symptomatic control of AF necessitating alternative rhythm control therapy. Outcome measures in DIO mice were pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride.Results: A total of 311 patients (mean [SD] age, 65 [12] years; 120 women [38.6%]) met the entry criteria and were treated with a class I or III AAD for symptomatic AF. Nonresponse to class I AADs in patients with obesity was less than in those without obesity (30% [obese] vs 6% [nonobese]; difference, 0.24; 95% CI, 0.11-0.37; P = .001). Both groups had similar symptomatic response to a potassium channel blocker AAD. On multivariate analysis, obesity, AAD class (class I vs III AAD [obese] odds ratio [OR], 4.54; 95% Wald CI, 1.84-11.20; P = .001), female vs male sex (OR, 2.31; 95% Wald CI, 1.07-4.99; P = .03), and hyperthyroidism (OR, 4.95; 95% Wald CI, 1.23-20.00; P = .02) were significant indicators of the probability of failure to respond to AADs. Pacing induced AF in 100% of DIO mice vs 30% (P < .001) in controls. Furthermore, DIO mice showed a greater reduction in AF burden when treated with sotalol compared with flecainide (85% vs 25%; P < .01).Conclusions and Relevance: Results suggest that obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers. These findings may have implications for the management of AF in patients with obesity.
AB - Importance: The association between obesity, an established risk factor for atrial fibrillation (AF), and response to antiarrhythmic drugs (AADs) remains unclear.Objective: To test the hypothesis that obesity differentially mediates response to AADs in patients with symptomatic AF and in mice with diet-induced obesity (DIO) and pacing induced AF.Design, Setting, and Participants: An observational cohort study was conducted including 311 patients enrolled in a clinical-genetic registry. Mice fed a high-fat diet for 10 weeks were also evaluated. The study was conducted from January 1, 2018, to June 2, 2019.Main Outcomes and Measures: Symptomatic response was defined as continuation of the same AAD for at least 3 months. Nonresponse was defined as discontinuation of the AAD within 3 months of initiation because of poor symptomatic control of AF necessitating alternative rhythm control therapy. Outcome measures in DIO mice were pacing-induced AF and suppression of AF after 2 weeks of treatment with flecainide acetate or sotalol hydrochloride.Results: A total of 311 patients (mean [SD] age, 65 [12] years; 120 women [38.6%]) met the entry criteria and were treated with a class I or III AAD for symptomatic AF. Nonresponse to class I AADs in patients with obesity was less than in those without obesity (30% [obese] vs 6% [nonobese]; difference, 0.24; 95% CI, 0.11-0.37; P = .001). Both groups had similar symptomatic response to a potassium channel blocker AAD. On multivariate analysis, obesity, AAD class (class I vs III AAD [obese] odds ratio [OR], 4.54; 95% Wald CI, 1.84-11.20; P = .001), female vs male sex (OR, 2.31; 95% Wald CI, 1.07-4.99; P = .03), and hyperthyroidism (OR, 4.95; 95% Wald CI, 1.23-20.00; P = .02) were significant indicators of the probability of failure to respond to AADs. Pacing induced AF in 100% of DIO mice vs 30% (P < .001) in controls. Furthermore, DIO mice showed a greater reduction in AF burden when treated with sotalol compared with flecainide (85% vs 25%; P < .01).Conclusions and Relevance: Results suggest that obesity differentially mediates response to AADs in patients and in mice with AF, possibly reducing the therapeutic effectiveness of sodium channel blockers. These findings may have implications for the management of AF in patients with obesity.
KW - Aged
KW - Animals
KW - Anti-Arrhythmia Agents/pharmacology
KW - Atrial Fibrillation/complications
KW - Diet, High-Fat
KW - Disease Models, Animal
KW - Female
KW - Flecainide/pharmacology
KW - Heart/drug effects
KW - Humans
KW - Logistic Models
KW - Male
KW - Mice
KW - Middle Aged
KW - Multivariate Analysis
KW - NAV1.5 Voltage-Gated Sodium Channel
KW - Obesity/complications
KW - Sex Factors
KW - Sotalol/pharmacology
KW - Treatment Failure
KW - Treatment Outcome
KW - Voltage-Gated Sodium Channel Blockers/pharmacology
U2 - 10.1001/jamacardio.2019.4513
DO - 10.1001/jamacardio.2019.4513
M3 - SCORING: Journal article
C2 - 31774463
VL - 5
SP - 57
EP - 64
JO - JAMA CARDIOL
JF - JAMA CARDIOL
SN - 2380-6583
IS - 1
ER -