1. Atrial Fibrillation in Women: Epidemiology and Management
Susan O’Donoghue, M.D.
Associate Director, Cardiac Arrhythmia Center
Director, Electrophysiology Fellowship

2. I/we have no real or apparent conflicts of interest to report.
Susan O’Donoghue, M.D.
I/we have no real or apparent conflicts of interest to report.

3. Atrial Fibrillation background
The most common pathologic arrhythmia
Affects 0.6% of U.S. population (~2.5 million Americans) today, ~16 million by 2050
Occurs in <1% of population ≤ age 60 but ~10% ≥ age 80
Incidence of AF increases with severity of CHF, valvular heart disease, hypertension

4. Atrial Fibrillation morbidity & mortality
Without anticoagulation, ischemic stroke rate: ~5% - 10% per year
~15% of all strokes occur in patients with AF (75,000 per year)
Total mortality rate is doubled in patients with AF vs. normal sinus rhythm

5. Atrial Fibrillation non-acute arrhythmia progression
Paroxysmal
Persistent
Stroke risk similar in all three categories
Hart et al. J Am Coll Cardiol 2000; 25:
Longstanding
Persistent AF

6. Management of AF in 2013
Thrombosis control
Rate control
Rhythm control

7. Atrial Fibrillation Issues in Women
Incidence of atrial fibrillation lower in women, but risk of stroke is higher
QT interval and risk of torsades higher in women
Special considerations for management of atrial fibrillation in pregnancy

8. Prevalence of Stroke by Age and Sex (NHANES: 2005–2008)
Population (%)
Prevalence of stroke jumps markedly at about age 60 and again at 80.
You saw this slide yesterday, but let’s put it in context for the elderly.
There is an increasing stroke risk in patients with AF with advancing age that is also multifactorial:
left atrial enlargement
reduced left atrial appendage (LAA) blood flow velocity
and evidence of blood stasis or “stagnation”
all of which predispose to thrombus formation.
Aging is a risk factor for atherosclerosis, and plaques in the aortic arch are associated with stroke independent of AF.
In the Stroke Prevention in Atrial Fibrillation (SPAF) studies, age was a more potent risk factor when combined with other risk factors such as hypertension or female gender, placing women over age 75 years with AF at particular risk for cardioembolic strokes.
Fuster V, et al ACCF/AHA/HRS Focused Updates Incorporated Into the ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation. J Am Coll Cardiol 2011;57:e
Age
Roger VL et al. Circulation 2010;123:e18-e209.

9. Stroke Risk by CHADS2 Score

10. CHADSVASc Stroke Risk Score
RISK FACTOR SCORE
CHF/LV dysfunction
Hypertension
Age 75 or above
Diabetes mellitus
Stroke/TIA/thromboembolus
Vascular Disease
Age
Female

11. CHADS VASc Stroke Rate
Score Stroke Rate % 2 2.2% 3 3.2% 4 4.0% 5 6.7% 6 9.8% 7 9.6% 8 6.7% %

12. Selection of Appropriate Anticoagulation

13. Newer Anticoagulants

14. Newer Anticoagulants
Advantages Immediate onset of action No blood testing Equal or superior efficacy to warfarin Disadvantages No antidote

15. QT Interval
Men – normal < 440 msec
Women – normal <460 msec

16. Overlap Between Normal and Pathologic QT Interval
Several factors may affect the baseline QT interval, including1:
- Genetics
Age and gender
- CNS disorders
- Electrolyte alterations
Certain medications
~33% of mutation- positive LQTS patients have a QT interval (≤ 480 msec) that overlaps normal, healthy individuals.2
Adapted from: Taggart NW, et al. Diagnostic miscues in congenital long-QT syndrome. Circulation. 2007;115: Cell. 2001;104:
References: 1. Maron BJ, Moller JH, Seidman CE, et al. Impact of laboratory molecular diagnosis on contemporary diagnostic criteria for genetically transmitted cardiovascular diseases: hypertrophic cardiomyopathy, long-QT syndrome, and marfan syndrome. Circulation. 1998;98: Taggart NW, Haglund CM, Tester DJ, Ackerman MJ. Diagnostic miscues in congenital long-QT syndrome. Circulation. 2007;115:

17. Drugs Associated With QT Prolongation
Quinidine
Procainamide
Disopyramide
Sotalol
Dofetilide
Amiodarone

18. The One-Two Punch of Pregnancy
Normal physiological changes actually increase risk of arrhythmias during pregnancy
Risk of thrombosis (blood clots) also increases with pregnancy
Managing anticoagulation presents challenges in the best of circumstances, but difficulties increase dramatically in pregnant women
As we have seen, normal physiological changes of pregnancy increase the risk of arrhythmias during pregnancy.
Formation of blood clots – or thrombosis – has long been recognized as a risk of pregnancy.
So, pregnancy packs a one-two punch: it increases the risk of arrhythmias while at the same time making clotting and embolic events a bigger risk.
Managing anticoagulation presents challenges in the best of circumstances, but the difficulties increase dramatically in pregnant women.

19. Pregnancy Safety Ratings for CV Drugs
What it Means
Drug
Class A
Safety established
(human studies)
None
Class B
Presumed safe (animal studies)
Beta-blocking agents (acebutolol, sotolol)
Class C
Uncertain safety
Digoxin, disopyridamide, flecanide, mexilitene, procainamide, propafenone, quinidine, beta-blocking agents (atenolol, labetolol, metoprolol, propranolol, diltiazem, verapamil
Class D
Unsafe
Amiodarone
The FDA has specifically listed a drug classification of typical cardiac medications used during pregnancy. Because most have uncertain safety – after all, there have been few randomized drug trials of pregnant women – the emphasis is on using only those drugs that are necessary and only at the lowest possible effective doses.
Admittedly, that is easier said than done since – as we mentioned – drug doses may need to be modified during pregnancy because pregnancy can alter the absorption, excretion and plasma concentration of antiarrhythmic drugs.

20. When AF Occurs During Pregnancy
Diagnosis and treatment of underlying condition causing the arrhythmia first priority
Hyperthyroidism
Metabolite imbalances
For rate control, recommendations include digoxin, a beta-blocker, or a nondihydropyridine calcium channel blocker
In a pregnant woman who develops AF, diagnosis and treatment of the underlying condition causing the arrhythmia are the first priorities.
For example, hyperthyroidism – often referred to as an "overactive thyroid“ – is a condition in which the thyroid gland makes too much thyroid hormone and is treatable.
Metabolite imbalances can cause an episode of AF and can be managed by treating the imbalance.
The heart rate should be controlled with digoxin, a beta-blocker, or a nondihydropyridine calcium channel blocker.

21. ACC-AHA Guidelines for Managing AF
All currently available AADs could potentially cross the placenta and enter breast milk; avoid if possible
Quinidine, sotalol, flecainide, and amiodarone successfully used during pregnancy in small number of cases
Quinidine has longest record of safety in pregnant women and remains the agent of choice for pharmacological cardioversion of AF in pregnancy
That was rate control, what about rhythm control?
Because all currently available antiarrhythmic agents have the potential to cross the placenta and later enter the breast milk, the guidelines indicate these drugs should be avoided if possible.
There are some drugs that have been used successfully during pregnancy but most of the data are from relatively small numbers of cases.
Quinidine, an antiarrhythmic first described in the 18th century, has the longest record of safety in pregnant women.

22. Anticoagulation in Pregnancy
Warfarin: contraindicated in pregnancy
Heparin: usually considered safer for the fetus (not necessarily safer for the mother)
Unfractionated heparin or low-molecular-weight heparin: efficacy for preventing stroke during pregnancy is not established
Because pregnancy is a pro-thrombotic state, using some sort of anticoagulation prophylaxis is recommended in women with AF.
Use of warfarin, the most common vitamin K antagonist used in the United States, is usually contraindicated during pregnancy because it crosses the placenta and has been associated with spontaneous abortion, embryopathy, and prematurity.
As warfarin crosses the placenta, the fetus is exposed to a higher dose than the mother because it has not yet developed a full complement of liver enzymes to process the drug; plus, particularly during the first trimester, the fetus has much lower levels of vitamin-K-dependent clotting factors.
Consequently, anticoagulation with warfarin is contraindicated in pregnancy.
Because heparin does not cross the placenta, it is often considered safer for the fetus than warfarin during pregnancy, but its long-term use in this setting increases hemorrhagic and thromboembolic risks to the mother.
The safety and efficacy of subcutaneous unfractionated heparin or low-molecular-weight heparin in preventing ischemic stroke in patients with AF during pregnancy have not been proved.

23. Guidelines: Anticoagulation in Pregnancy
Heparin may be considered during the first trimester and last month of pregnancy for patients with AF and risk factors for thromboembolism
Despite the limited data available, subcutaneous administration of low-molecular-weight heparin may be considered during first trimester and last month of pregnancy for patients with AF and risk factors for thromboembolism
Administration of an oral anticoagulant may be considered during second trimester for pregnant patients with AF at high thromboembolic risk
We’re not going to go through these recommendations from the 2011 updated AF guidelines, except to say that management varies during the pregnancy in order to balance risk and benefit to the mother and to the developing fetus.
Vitale N, De Feo M, De Santo LS, et al. Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol. 1999;33:
Hanania G. Management of anticoagulants during pregnancy. Heart. 2001;86:125-6.
Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000;160:191-6.
Fuster V, Rydén LE, Cannom DS, et al ACCF/AHA/HRS focused updates incorporated into the ACC/AHA/ESC 2006 Guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in partnership with the European Society of Cardiology and in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. J Am Coll Cardiol 2011;57:e

24. Catheter Ablation

25. Atrial Flutter

26. PV isolation

27. Left atrial catheter ablation
Isolate both pairs of veins plus mitral isthmus and posterior atrial ablation

28. Summary – Atrial Fibrillation in Womem
Women have a lower incidence of atrial fibrillation, but a higher incidence of stroke
Anticoagulation recommendations may be different for women (CHADS2VASC)
African American women are under-represented in Afib trials, thus risk:benefit uncertain
Women are at a higher risk of proarrhythmia related to QT prolongation
Afib in pregnancy presents unique challenges