Women and Heart Disease: The Association Between Females and AF

Podcast Transcript

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Welcome to Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic. This podcast will explore the latest innovations, medical and surgical treatments, diagnostic testing, research, technology and practice improvements.

Mohamed Kanj, MD:

Today, for the next 15 minutes or so, we'll talk about the gender-based differences in atrial fibrillation.

Let's talk about the epidemiology of atrial fibrillation. If you look at atrial fibrillation, you see more women having atrial fibrillation than men. Then you ask yourself why that is. The first reason is simply because women live longer than men. As you very well know, atrial fibrillation is a disease that gets more frequent as we get older.

Because women have longer longevity, we expect to see more atrial fibrillation in women than in men. However, there are certain risks that predispose women to have atrial fibrillation. These could be hormonal, adiposity, fat distribution, as well as structural changes that we see inside the heart. For example, women are more prone to have left ventricular hypertrophy. They are more prone to have epicardial fat. There is a strong association between epicardial fat and atrial fibrillation and the recurrence of atrial fibrillation. We see more atrial fibrosis in the left atrium as well as higher levels of CRP, inflammatory agents that predispose people to atrial fibrillation. Also, women have more risk factors that predispose them to atrial fibrillation hypertension, valvular heart disease, thyroid disease, as well as sensitivity to alcohol.

It also could be an unjustified bias that we think women have more atrial fibrillation. Alcohol and gender have been well studied, and it is clear that alcohol can precipitate atrial fibrillation at a much lower dose in women compared to men by causing more fibrosis, inflammation and all that stuff

Do women have a different presentation when they have atrial fibrillation compared to men?

There's a little bit of difference. One, as we said, women usually present with atrial fibrillation when they’re a little bit older. When they have atrial fibrillation, their heart rate is faster. In the early part of atrial fibrillation, usually their atrial fibrillation is shorter in duration compared to men, but they are more symptomatic. When they have atrial fibrillation, the degree of symptoms is much greater than what we see with men.

If you look at patients who have atrial fibrillation and compare women versus men, you see that the impact of atrial fibrillation on the individual is more pronounced in women than in men, both at the level of mental health and physical health. Then you ask yourself this question: is it gender or is it actually true?

It is actually true. When you compare women who have ablation versus women who don't have active ablation, you also see a very big impact of atrial fibrillation. It looks like it's true that fibrillation has a bigger impact and more symptoms in women than men. That also could be because of the prevalence of diastolic heart failure, left ventricular hypertrophy where patients need their atrial kick.

So in summary, in presentation, women are more symptomatic. They usually present a little bit older and have a later presentation.

What about atrial fibrillation therapy? The four pillars of ablation therapy are prevention, stroke prevention, rate control and rhythm control. What we know is that in both women and men, if you control blood pressure, you decrease the chances of recurrence. You decrease the chances of progression. You decrease the changes of bad outcomes from atrial fibrillation. SGL2 inhibitors have been shown to decrease episodes of atrial fibrillation. Controlling sugar is also very important in women, decreasing recurrence, progression and AFib outcomes. Weight loss has the same effect in women; it decreases the risk of recurrence and progression. Staying away from alcohol, as well as treating sleep apnea.

What about rate control? Guidelines tell us that we have to do rate control, but we don't have to be very aggressive in rate control. The goal is to get the heart rate between 80 to 100, not less than 80, because we get into trouble. We usually use beta blockers, calcium channel blockers and digoxin. Rarely, we go to AV node ablation in the elderly.

However, when we look at how we're doing with rate control by gender. What we see when we tried rate control in women versus men, women become more symptomatic from the side effects of these drugs compared to men. When we gave digoxin, it was associated with higher rates of mortality. That's because women are more predisposed to digoxin-induced arrhythmias. Digoxin could also increase the risk of cancers like breast and uterine cancer.

We’ve seen that the prevalence of using AV node ablation and pacemakers in women is higher in the general population. At the same time, complication rates from pacemakers in women are much higher. We see more complications from rate control medications. We have more complications with pacemakers.

To summarize rate control: women are more likely to get rate control than men. They have higher risks of side effects and higher chances of getting a pacemaker. When they get a pacemaker, they have a much higher rate of complication.

Let’s talk a little about rhythm control. We now know that rhythm control is a better strategy. There are two kinds: antiarrhythmic medication and catheter ablation. From the EAST AFNET study, when we looked at early atrial fibrillation, if we do rhythm control strategy, it’s associated with better mortality, less stroke, less heart failure and less hospitalization.

When we look a meta-analyses of all these clinical trials, what we see is that rhythm control strategy has a much better impact on mortality than rate control. You see a lower risk of mortality by around 15%. When we look at stroke and hospitalization, heart failure and hospitalization, we see the same thing. Rhythm control strategy in women as well as men has a better outcome when it comes to stroke as well as heart failure hospitalization.

What we know is that we need to offer a rhythm control strategy. However, there is a gender difference in the efficacy of rhythm control strategy between women and men. For example, in men, what we see is that you have at least, a year or 13 month where they have persistent atrial fibrillation before the success rate of atrial fibrillation ablation starts getting ahead. Meaning, you have to do a rhythm control strategy, but you have up to a year to offer that rhythm control strategy.

But in women, that inflection point, the chances to have a failed ablation or or failed antiarrhythmic medication, comes much earlier, within the first three months. If you see a woman with atrial fibrillation, you need to offer rhythm control much earlier than you would for a man. Because otherwise you start losing the success rate of rhythm control strategy.

Women are less likely to be offered rhythm control and more likely to receive rate control. This could be due to bias, older age at presentation or more cardiovascular comorbidities. But it is true.9

At the same time, what we know is rhythm control, antiarrhythmic medications are associated with higher risks of complications in women versus men. For example, torsades de pointes (meaning polymorphic ventricular tachycardia) is more common in women compared to men. The risk of bradycardia on amiodarone is much higher with women than men.

If you want to start antiarrhythmic medication, you must begin at a lower dose, especially with drugs like amiodarone. Women are also less likely to be offered DC cardioversion to restore sinus rhythm.

When we look at national data, and we see ask are we having bias in referring patients to catheter ablation? When we look at women versus men, what is clear is that men are more likely to be referred to AFib ablation than women. This is more of a national study. In academic centers, we have not seen that difference between offering a rhythm control strategy with AFib ablation in men versus women. Nationally, however, women are 15–20% less likely to be offered an atrial fibrillation ablation. This could be due to referral bias or women declining invasive procedures. Could be a complex strategy we aren’t sure how to analyze.

What about success rate of this procedure? What’s clear is AFib ablation is more successful in men than in women. We’re still trying to understand why. It could be due to comorbidities or the fact that women are more likely to have atrial fibrosis or atrial myopathy.

So, there could be a lot of reasons why women have lower success rates. It could be that there's a bias and we're offering it only when women are becoming much older. But we clearly see a few like atrial fibrosis. We see shorter atrial refractory periods, more epicardial fat that's been associated with lower chances of success rate. We’ve seen wider dispersion in conduction velocities in the atrium as well as the ventricle. We've seen more complex electrograms telling us that there's more advanced atrial myopathy.

More importantly, electrophysiology studies show more non-pulmonary vein triggers in women, meaning fibrillation comes from all over the atrium and not just localized to the pulmonary vein.

What about complications? Unfortunately, we’ve seen a trend women have a higher risk of complications from invasive procedures. However, even though they have higher risk of complication, even though they are less likely to have a successful procedure, still, it's much better to offer rhythm control strategy in atrial fibrillation that leave them with rate control.

As shown in the AFNET study, arrhythmia control with rhythm strategy has been associated with lower mortality, stroke and heart failure hospitalization.

The last thing we want to talk about is stroke prevention. We have two strategies: warfarin and DOACs. If someone has valvular atrial fibrillation, we give warfarin. If not, we use the CHA₂DS₂-VASc score. DOACs are better than warfarin in non-valvular fibrillation, with lower mortality and intracranial bleeding.

We’ve used the CHA₂DS₂-VASc score for a while. If it’s 0 in men and 1 in women, we do nothing. If it’s 1 in men and 2 in women, we consider anticoagulation. If it’s more than 1 in men or more than 2 in women, we prescribe oral anticoagulation.

Does gender matter? We add gender to increase the CHA₂DS₂-VASc score, but subtract it when making decisions. For example, to recommend anticoagulation, we say more than one in men, more than two in women.

So, what’s the story with this? Is gender a real risk or is it not a real risk? Actually, we think that it's more of a risk modifier and not a real risk for stroke prevention. It does not necessarily cause stroke. It amplifies the risk factors if somebody has AFib.

When comparing men and women with low to moderate CHA₂DS₂-VASc scores, gender doesn’t add significantly to the risk of stroke. Only at high scores does female gender add to stroke risk. In these cases, we recommend anticoagulation anyway.

There are some thoughts of actually dropping gender from the CHA₂DS₂-VASc score and applying the same risk to both of these individuals. But this is a work in progress.

Women are less likely to be prescribed oral anticoagulation after HF ablation. They have higher risk of bleeding when taking warfarin. We see more risk of GI bleeding when they’re taking DOACs. But the more important thing is that women actually are very compliant on these drugs, which is very good.

One thing is very important, we see also underdosing in women. That's more than what we see in men. We have to be worried about that because lower dose of DOACs has been associated with higher rate of mortality and stroke.

What about closure [left atrial appendage occlusion] devices? We see clearly that the risk of doing, for example, for your left atrial appendage closure device has been associated with higher risk of complications in women compared to men and associated with a longer hospital stay. However, if the patient ends up getting it, we did not see any difference in outcome.

So again, for the same thing, procedures and antiarrhythmic medications and rate control strategies, all have been associated with more complications, but they still have benefits. We should not be not offering these lifesaving procedures or lifesaving medications to women versus men.

In summary, when it comes to stroke prevention, we know that women are less likely to get oral anticoagulation. Or if they get it, they get lower doses. There's higher risk of complications with procedures as well as with anticoagulation. But I’m not trying to say that we should not be offering these life-saving medications and life-saving procedures. We just have to be careful about doing these procedures.

A few final words about atrial fibrillation and pregnancy. It looks like infertility and high parity are associated with more atrial fibrillation. The sweet spot seems to be two to three kids. Less than that, more AFib. More than that, more atrial fibrillation.

Usually, the onset of atrial fibrillation occurs at the third trimester or shortly after delivery. Often, there are preexisting condition, whether OB-GYN or cardiac, that predispose patients. Cardioversion is safe during pregnancy. Antiarrhythmic medications are safe during pregnancy. Oral anticoagulations are safe during pregnancy. But, we usually like low molecular weight heparin because it doesn't cross the placenta. It's probably one of the safest strategy.

We still use the CHA₂DS₂-VASc score when recommending oral anticoagulation in pregnant women. However, there is a higher risk of thromboembolism that’s more pronounced than what the CHA₂DS₂-VASc actually reflects. For mechanical valves, we use low molecular weight heparin in the first trimester, then switch to warfarin. Or we give them warfarin if the dose can be kept under five milligrams. But you have to do a shared decision making with the individual to make sure they understand the risks and benefits.

One thing, if you want to give low molecular weight heparin, sometimes we recommend measuring anti-Xa inhibitor levels just to make sure that they're getting the right the right dose. If breastfeeding, there's nothing better and safer than warfarin for that.

In summary, despite high symptomatology and risk factors, rhythm control is less likely to be offered to women. Despite higher stroke risk and the safety of oral anticoagulation, oral anticoagulation or left atrial appendage occlusion are less likely to be prescribed.

I want to emphasize this. Early intervention is key. Use shared decision-making with your patients.

We see more women in the population. The duration of symptoms is more with women. It has a bigger impact on quality of life in women. We have higher risk of stroke in women. You have higher risk of mortality when you do procedures and anticoagulation in women. Risk of arrhythmia with antiarrhythmic medication is higher with women, and risk of complications with procedures is also higher with women.

With that, I’d like to conclude. Thank you very much for the invitation.

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