Disclosures. Objectives. Gender and Electrophysiology. Gender and Electrophysiology. Increasing Prevalence 10/16/2014

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1 Atrial Fibrillation in Postmenopausal Women: Risk Factors, Diagnosis and Management Anita M. Kelsey, MD, FACC, FASE Director, Echocardiography Director, Women s Heart Program Medical Director, School of Cardiac Ultrasound Saint Francis Hospital and Medical Center, Hartford, Connecticut Associate Professor of Medicine, (SFHMC) University of Connecticut NAMS 2014 None Disclosures Objectives Gender and Electrophysiology Background information about gender and atrial fibrillation (AF) Risk factors for AF Diagnosis of AF Management of AF Women have higher resting heart rates shorter sinus node recovery times after overdrive pacing longer corrected QT interval:(qt C ) = QT Interval / (RR interval) Boys and girls begin with similar QTc intervals After puberty the male QTc interval shortens BazettHC. An analysis of the time-relations of electrocardiograms. Heart. 1920: 7; Gender and Electrophysiology Increasing Prevalence During mental stress, women develop shorter refractoriness in the atrial tissue and less shortening of the QTc interval Atrial refractoriness is shortened significantly in both postmenopausal women and in men during simultaneous atrioventricularpacing Not demonstrated in premenopausal women Cha YM, et al Arrhythmias in Women Diagnosis and Management 2014 Approximately 2.3 million US adults currently have atrial fibrillation Estimated to increase to greater than 5.6 million by 2050 >50% of affected individuals will be >80 years old Go AS, et al. Prevalence of Diagnosed Atrial Fibrillation in Adults: National Implications for Rhythm Management and Stroke Prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:

2 Men vs Women Advanced Age Approximately equal numbers of men and women affected Higher prevalence among men Go AS, et al. Prevalence of Diagnosed Atrial Fibrillation in Adults: National Implications for Rhythm Management and Stroke Prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285: % of patients with AF over age 75 are women Go AS, et al. Prevalence of Diagnosed Atrial Fibrillation in Adults: National Implications for Rhythm Management and Stroke Prevention: the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285: Variable Clinical Presentation Stroke in Women vs. Men +/-AF Women at first AF presentation: 5 years older Faster rate Fewer h/o MI More HTN Hazard Ratio of AF on stroke in women vs. men 4.5 (95% CI 2.2 to 9.2) Humphries, KH, et al. New-Onset Atrial Fibrillation: Sex Differences in Presentation, Treatment, and Outcome. Circulation. 2001;103: ) FribergJ, et al. Comparison of the Impact of Atrial Fibrillation on the Risk of Stroke and Cardiovascular Death in Women Versus Men (the Copenhagen City Heart Study). Am J Cardiol2004;94: AF and Mortality RISK FACTORS Hazard Ratio of AF on cardiovascular mortality in women vs. men 2.9 (95% CI 1.7 to 4.8) FribergJ, et al. Comparison of the Impact of Atrial Fibrillation on the Risk of Stroke and Cardiovascular Death in Women Versus Men (the Copenhagen City Heart Study). Am J Cardiol2004;94:

3 Risk Factors for AF Hypertension More prevalent in women than men Often poorly controlled in older women (23% of women, 38% of men >80 years have BP <140/90 JNC 8 Goal < 140/90 Except DM,CKD, < 130/80 Benjamin EJ, Levy D, Vaziri SM, D Agostino RB, Belanger AJ, Wolf PA. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA. 1994;271: Bushnell C, et al. Guidelines for the Prevention of Stroke in Women A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2014: May;45(5): (JNC 8). JAMA. 2014;311(5): Smoking Rotterdam Study Current and former smoking increases risk No difference between men and women Most common underlying disorder in patients with AF in developed countries Less common but frequently underdiagnosed in women AF may be seen during acute MI but rarely in the absence of additional signs or symptoms. Ischemic Heart Disease Heeringa, Kors JA, Hofman A, et al. AHJ 2008: 156(6): , Cigarette smoking and risk of atrial fibrillation: The Rotterdam Study Saint Francis Hospital and Medical Center, Hartford, CT Valvular Heart Disease Heart Failure Echocardiographic image of rheumatic mitral valve stenosis Any stenotic heart valve predisposes a woman to AF Rheumatic heart disease, now uncommon in developed countries still represents significant global risk factor MS, MR, TR in combination is associated with the highest incidence of AF Women with AF are more likely to have HFpEFand less likely to have systolic dysfunction Chronic AF can lead to HF Chronic HF can predispose to AF. 3

4 Hyperthyroidism Must check a TSH (tx if < 0.1 microunit/ml) Also increased risk for AF with subclinical hyperthyroidism especially in patients over 65 years, postmenopausal with low bone mass, tachyarrhythmias or heart disease Obesity Risk of AF in women with BMI was 2.0 x a normal weight woman Risk of AF in women with BMI > 35 was 3.5 x that of a normal weight woman Mechanism is left atrial dilation Sawin CT, Geller A, Wolf PA, et al. Low Serum Thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. NEJM 1994; 331:1249 Wang TJ et al, Obesity and the risk of New Onset Atrial Fibrillation. JAMA. 2004;292: Karasoy D et al, "Obesity is a powerful predictor of atrial fibrillation in women" Eur Heart J 2012; Diabetes Framingham Heart Study: DM was associated with increased risk of development of AF in men and women (OR 1.1 and 1.5) Increased LV mass and increased LV stiffness have been put forth as possible mechanisms Benjamin EJ et al. Independent risk factors for atrial fibrillation in a population-based cohort. The Framingham Heart Study. JAMA 1994:271;60:850 Devereux RB et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000; 101:2271 Menopause Framingham Heart Study: Early menopause was not associated with increased risk of AF WHI: A modest, statistically significant increase in the risk of atrial fibrillation (AF) was evident for women who had previously undergone hysterectomy and were treated with estrogen monotherapy compared with placebo. Magnani JW et al. Age of Natural Menopause and Atrial Fibrillation. Am Heart J. Apr 2012; 163(4): Perez MV, et al.effects of postmenopausal hormone therapy on incident atrial fibrillation: the Women's Health Initiative randomized controlled trials. CircArrhythm Electrophysiol Dec;5(6): Family History Genetic Factors Birth Weight Inflammation and infection Pericardial Fat Autonomic dysfunction Corrected QT interval PAC s HOCM Metabolic Syndrome Chronic Kidney Disease Surgery Other Factors Congenital Heart Disease SVT Low serum Magnesium Caffeine Fish and Fish Oil Supplements Medications Regular physical exercise Air pollution Venous thromboembolic disease OSA Ethnicity ETOH Does optimizing risk factors reduce AF incidence? Risk factors HTN, BMI, DM, smoking and CVD were categorized into optimal, borderline or elevated levels for mean f/u 17.1 years, 14,598 pts As with other forms of cardiovascular disease, more than half of the AF burden is potentially avoidable through the optimization of cardiovascular risk factors levels Huxley RR, et al. Absolute and Attributable Risk Factors of Atrial Fibrillation in Relation to Optimal and Borderline Risk Factors: Atherosclerosis Risk in Communities (ARIC) Study. Circulation April 12, 2011: 123(14):

5 DIAGNOSIS Stroke 2014: May;45(5): Stroke Prevention in Women: A Statement for Healthcare Professionals from the American Heart Association/American Stroke Association Stroke. 2014; 45(5): Guidelines Class I: Considering the increased prevalence of AF with age and the higher risk of stroke in elderly women with AF, active screening (in particular of women >75 years of age) in primary care settings using pulse taking followed by an ECG as appropriate is recommended Level of Evidence B Guidelines for the Prevention of Stroke in Women: A statement from Healthcare Professionals from the American Heart Association/American Stroke Association. Stroke 2014: May;45(5): What is the rhythm? Atrial Fibrillation P waves absent. Atrial activity is totally irregular. Fibrillatory (f) waves of varying amplitude, duration and morphology, cause random oscillation of the baseline. Ventricular rate is bpm (unless controlled by medication) Ventricular rhythm is irregularly irregular 5

6 What is the rhythm? Atrial Flutter Rapid regular atrial undulations (flutter or F waves) at bpm. Typical atrial flutter morphology usually presents in Leads II,III, AVF: Inverted F waves without an isoelectric baseline ( picketfence or sawtooth appearance) AV conduction ratio (of flutter waves to QRS complexes) is fixed, usually 2:1, 4:1. Ventricular rate may be regular. General Evaluation MANAGEMENT History and Physical Chest X Ray ECG Transthoracic Echocardiogram Thyroid function tests Comprehensive metabolic panel In the proper clinical setting, cardiac enzymes Reduce risk of thromboembolism Rate control + Rhythm Control Goals of Treatment Class I: Guidelines In patients with AF, antithrombotic therapy should be individualized based on shared decision making after discussion of the absolute risks and relative risks of stroke and bleeding and the patient s values and preferences. Level of Evidence: C Anderson JL, et al. Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations) Circulation. 2013;127: ) 6

7 Guidelines American College of Cardiology AnticoagEvaluator Warfarin to target INR (2-3 or ) Mechanical heart valve Significant valve disease No therapy Low risk (0) NonvalvularAF Anticoagulation CHA 2 DS 2 VASc ASA CHA 2 DS 2 VASc Score OAC Intermediate risk (1) ASA High risk (>2) OAC ASA = Aspirin OAC = well controlled warfarin (INR 2-3), or (apixaban, rivaroxaban or dabigatran) Mechanism Dabigatran (RE-LY) Rivaroxaban (ROCKET-AF) Direct thrombin inhibitor Direct factor Xa inhibitor Bioavailability, % Time to peak, h Half-life, h Apixaban (ARISTOTLE) Direct factor Xa inhibitor Excretion 80% renal 2/3 liver, 1/3 renal 25% renal, 75% fecal Dose 150 mg BID 20 mg OD 5 mg BID Dose in renal impairment 110 mg BID 15 mg OD (if CrCl30 49 ml/min) 2.5 mg BID # patients 18,113 14,264 18,201 Follow-up period 24 months 40 months 40 months Randomized groups New Oral Anticoagulants Warfarin vs. blinded doses of dabigatran (150 or 110 mg BID) Warfarin vs. rivaroxaban20 mg OD Warfarin vs. apixaban5 mg BID Lip GY, et al. Indirect comparisons of new oralanticoagulant drugs for efficacy and safety when used for stroke prevention in atrial fibrillation. J Am CollCardiol Aug 21;60(8): Guidelines Class I New oral anticoagulants are a useful alternative to warfarinfor the prevention of stroke and systemic thromboembolism in women with paroxysmal or permanent AF and prespecifiedrisk factors (according to the CHADSVASC) who do NOThave a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure(crcl<15 ml/min), lower weight (<50kg) or advanced liver disease(impaired baseline clotting function). Level of Evidence A Bushnell C, et al. Guidelines for the Prevention of Stroke in Women A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2014: May;45(5): Appropriate Tx Underprescribed Men n = 1,319 Women n = 1,094 Sex difference n (%) n (%) p All antithrombotic agents 1,223 (92.7) 978 (89.4) Anticoagulant agents 806 (61.1) 567 (51.8) <0.001 Antiplatelet agents 822 (62.3) 688 (62.9) 0.77 Aspirin 800 (60.7) 672 (61.4) 0.70 WändellP, et al. Effects of prescribed antithrombotics and other cardiovascular pharmacotherapies on all-cause mortality in patients with diabetes and atrial fibrillation a cohort study from Sweden using propensity score analyses. Diabetology & Metabolic Syndrome 2014, 6:2. 7

8 Rate Control RATE VS RHYTHM CONTROL Rate vs Rhythm Control Strategies for Rhythm Control End Points (HF, thromboembolic complications, and adverse effects of antiarrhythmic drugs Rate Control Rhythm control Rienstra M, Van Veldhuisen DJ, Hagens VE et al. Gender-Related Differences in Rhythm Control Treatment in Persistent Atrial Fibrillation: Data of the Rate Control vs Electrical Cardioversion (RACE) Study JACC (7):

9 Transesophageal Echo (TEE) If < 48 hours in AF can cardiovert without TEE If > 48 hours of AF without adequate anticoagulation, must undergo TEE prior to any attempt at rhythm control Conclusions Women with AF have worse prognosis with increased strokes, and increased mortality c/w men Women have an increased risk factor burden New guidelines recommend active screening for AF especially women >75 years of age CHA 2 DS 2 VASc provides improved risk stratification for stroke risk in women Rate control strategy is appropriate in women Call to Action More aggressive and earlier diagnosis and treatment of AF in postmenopausal women Increased Risk Factor modification Treatment with OAC s when appropriate Early referral to Cardiology 9