 Hello everyone, my name is Heather Pemberton and I'm one of the Chief Cardiology Fellows here at Texas Heart Institute and I'll be talking to you today about pregnancy and cardiovascular disease. And I just want to preface this talk by letting everyone know that pregnancy is generally very well tolerated and women soar throughout pregnancy and the hard part starts after the baby is actually born. But for those patients with pre-existing cardiac or aortic disease, we just want you to know a little bit about your risk, ensure that you have appropriate follow-up and know that you have a team behind you throughout your entire pregnancy. So let's get started. So just some background information about cardiovascular disease and pregnancy. So it is increasing in the western world affecting about one to four percent of pregnancies in the U.S. And this is mainly due to two main causes. So one, we're having babies later in life so we have to advance in maternal age. This gives us time to accumulate some of those risk factors like diabetes, hypertension and obesity. And two, many women of childbearing age have congenital heart disease and this actually accounts for about 80 percent of all pregnancies in women with known heart condition. So these patients have received operative care earlier in life and they're making it to childbearing ages and so they have some complications with pregnancy later in life. And in developed nations, maternal heart disease is the leading cause of death during pregnancy. So if you look to the graphs to your right, this looks at the deaths during pregnancy in mothers. And you can see here the red arrow highlights that cardiovascular disease is the leading cause of maternal death in the western world. So in order to understand what can go wrong in pregnancy, we kind of have to understand the physiologic adaptation to the pregnant state. So there are several hemodynamic changes in pregnancy. So pregnancy is a high output cardiovascular state that is associated with many changes including decreased systemic vascular resistance or how much your blood vessels dilate. Your blood pressure stays relatively the same although some patients with high blood pressure prior to pregnancy actually experience normal pressures during pregnancies because those blood vessels dilate. We also have expanded blood volume, increased heart rate, significant increase in your cardiac output or how much blood the heart is pumping per minute. And these changes all allow for optimal growth and development of the fetus and protect the mother from risk of delivery. There are also some major changes in the blood volume and the coagulation cascade or your clotting cascade. So there is expansion of the plasma volume and an increase in red cell mass that begins around the fourth week of gestation and peaks around 28 weeks or 34 weeks. The plasma volume or the amount of fluid in those blood in the blood vessels increases more than your red cell mass and this leads to a relative anemia of pregnancy. So it is actually normal to be anemic during pregnancy. The total intravascular volume actually increases by about 50% above non-pregnant values. There are also many changes in the coagulation cascade in pregnancy and I put this here just for your reference but the big picture is that the clotting factors or the things that promote clotting increase and the things that block clot from forming actually decrease and this leads to a pro clotting or a hyper coagulable state. So how do we risk do risk estimation for pregnancy and what is the importance of counseling? So all women with known cardiac or aortic disease who wish to become pregnant require timely pre-pregnancy counseling. This is a multi-disciplinary management plan that should be constructed and discussed with you the patient. Unhealthy habits such as smoking, alcohol intake, diet and exercise should be addressed as these directly impact maternal and fetal outcomes. So the risk of maternal cardiovascular complications depends on many things and this is a very busy slide but I'll break it down for you. So it really depends on the type of cardiovascular disease present, how the ventricle looks, how the valves look, how symptomatic the patient is if there's a presence of cyanosis or low oxygen saturation. Is there high blood pressure in those pulmonary arteries and then other comorbid conditions such as hypertension or diabetes? There's several risk calculators that we use to help determine what your risk is during pregnancy. Probably the most common ones that are used are CarPreg2, Zahara and the gold standard modified World Health Organization classification and that's the one that's probably most comprehensive and the one that we utilize the very most. So just a background about CarPreg2, so this was a study that prospectively enrolled 1,900 pregnancies with known heart disease and determined their outcomes during pregnancy. A multivariate analysis was performed to identify predictors of cardiac complications and these were incorporated into a risk index. There were 10 predictors in this study that they found predicted maternal cardiac complications. Five general predictors, which I have listed here. Four lesion specific predictors such as mechanical valves, aortic disease, pulmonary hypertension, the presence of coronary artery disease or blockages in the arteries prior to pregnancy and then one delivery of care predictor, which essentially was did we detect them early in pregnancy or later in pregnancy and later was worse. And then you added up this score and then you can calculate your risk of having a maternal cardiac event. Zahara was very similar to the CarPreg2 score. It just looked at patients with congenital heart disease and then again developed a risk classification and stratified the patients based on their risk score. The Modified World Health Organization classification is the one that we utilize most often and it's probably the most comprehensive. So I'm going to go through this for you kind of ad nauseam but it provides you a lot of information and I think it's very useful. So the Modified WHO Group 1 or your low risk group, these are the disease states that are associated with it but it's really just simple congenital lesions that have been repaired or mitral valve prolapse. These patients have no increased risk of maternal morbidity or mortality. The maternal cardiac event rate is only about two to five percent, requires infrequent follow-ups about one to two times during pregnancy and these patients can deliver at the local hospital. And when I talk about maternal cardiac event rates, this is what I'm talking about. So it's either death due to heart disease, clinically significant heart failure, vascular events such as a stroke or a heart attack, the need for an urgent or invasive cardiovascular intervention during pregnancy, symptomatic arrhythmia, requiring treatment, thromboembolic events such as a clot, systemic embolism, valve thrombosis, infection of your heart valves, or worsening of your symptoms. So that's what I'm referring to when I'm talking about maternal cardiac events. So let's move on to your WHO class 2 or your low to moderate risk patients. So the disease states and these are several but they include unoperated atrial ventricular septal defects, super ventricular arrhythmias, among others. There's a small increase in maternal mortality and a moderate increased risk of morbidity. Maternal cardiac event rate is about five to ten percent. This requires a little bit more frequent follow-up about one times per trimester. But these patients can still safely deliver at a local hospital. Now we're moving on to your moderate risk patients. So again, there's many disease states associated with this and I just left that there for your reference. But these patients have an intermediate increased risk of maternal mortality and a moderate to severe increased risk and morbidity. The maternal cardiac event rate for these patients is about 10 to 20%. These patients need frequent follow-up and many require hospitalization at specialized centered for delivery. Now we're moving on to your high risk patients. So again, several disease states but I'll point out a couple. So mechanical valves fall in this category. Moderate mitral stenosis falls in this category. Severe asymptomatic aortic stenosis and your peripartum cardiomyopathies or heart failure that develops during pregnancy without any residual impairment falls into this category. There's significantly increased risk of maternal mortality and severe increased risk of morbidity. These patients have a high cardiac event rate of 19 to 27%. They need very frequent follow-up and again, they need delivery at a specialized center for pregnancy and cardiac disease. And lastly, your extremely high risk patients. Again, many disease states, I'll point out a couple. Severe mitral stenosis, your severe symptomatic aortic stenosis. These are your pulmonary arterial hypertension patients and then anyone with really bad heart failure fall into this class. These patients are at extremely high risk of maternal mortality and severe morbidity during pregnancy. The cardiac event rate is 40 to 100%. Unfortunately, in these group of patients, pregnancy is contraindicated. And if pregnancy occurs, termination should be discussed. They require, if they choose to become pregnant, they require very, very, very close follow-up. And delivery must occur at an expert center for pregnancy and cardiovascular disease. Now that we've kind of gone over the WHO criteria, I'm gonna go over some of the more common complications that we see during pregnancy and far and away, the most common one is hypertensive disorders. So this affects about 5 to 10% of pregnancies worldwide. It's a major cause of maternal fetal and neonatal morbidity and mortality, with several maternal risks, including placental abruption, stroke, and multi-organ failure. Fetal risks include intrauterine growth retardation, prematurity, and intrauterine death. So we need to pay attention to our blood pressure during pregnancy. Hypertensive disorders comprises of many different things. So pre-existing hypertension or hypertension that exists prior to pregnancy, occurs throughout pregnancy and then continues after pregnancy. Gestational hypertension, which is just hypertension or high blood pressure that occurs during pregnancy and stops once the baby is born. Pre-eclampsia, which I will go in further, and then a combination of multiple. So pre-eclampsia is gestational hypertension or high blood pressure with significant protein in your urine or hypertension with evidence of end organ dysfunction plus or minus protein in your urine. So end organ dysfunction, I mean they could have renal dysfunction or kidney dysfunction or liver dysfunction. Pre-eclampsia is usually secondary to fetal maternal vascular dysfunction. It's often associated with fetal growth restriction due to placental insufficiency, and it's a common cause of prematurity. There are several risk factors. So there are high risk features and there are moderate risk features. Some of the high risk features include hypertensive disease during or prior to pregnancy, kidney disease, autoimmune conditions, diabetes, chronic hypertension, and then I've listed some of your moderate risk features as well. The reason why we care is some high and moderate risk patients may benefit from low dose aspirin during their pregnancy. Unfortunately, the only cure for pre-eclampsia is delivery. And this is indicated when you have visual disturbances or chemostatic disorders or if you're asymptomatic and the baby is ready to be born then you would deliver at 36 weeks gestation. So how do we manage hypertension and pregnancy? Well drug therapy is indicated when the systolic blood pressure or the top number is greater than 140 and the diastolic blood pressure or the bottom number is greater than 90. The first line agents include beta blockers except the tenolil and calcium channel blockers. If the patient has severe hypertension or if that top number is greater than 160 to 180 and that bottom number is greater than 110, you need to be hospitalized and start on IV medication to bring that blood pressure down. If you have pre-eclampsia with evidence of fluid in your lung, then the first line agent is IV nitroglycerin. Now we're gonna move on to clotting disorders. So, fiendish thromboembolism is just a fancy way of saying clotting in pregnancy is actually very common. So the risk of developing a clot in pregnancy is about 40 to 50 times greater than the non-pregnant female population with a prevalence of about one in 1600 births. In fact, pulmonary embolism or a clot in the lungs is the leading cause of maternal death in the United Kingdom and is the fifth leading cause of maternal death overall. Most cases occur in the postpartum so after the baby is born. This is actually two to five times greater than the anti-partum period. So this during the pregnant period. There are multiple risk factors associated with it, including varicose veins, diabetes, obesity, advanced maternal age, hypertension, smoking, pre-eclampsia, if you need an emergency section, or if you have an inherited clotting disorder. So why does this occur? Well, pregnancy is a state where you have venous stasis and static blood means clotting blood. Endothelial injury, this is why it's very high in the postpartum period because you damage those cells when you have the baby and endothelial injury encourages clotting. And then you have changes in the body that actually promote clotting. So these three things combined make it so that your risk of developing a clot in pregnancy is much greater. So how do we treat these patients? Low molecular weight heparin is the treatment of choice. This is preferred in stable patients because it's easy to use, effective, and has a favorable safety profile, especially for the baby. You avoid these in patients with underlying kidney disease and you stop at it at least 24 hours prior to delivery to prevent further bleeding. Unfractionated heparin is a form of IV blood thinner. We use these typically in patients who are unstable or have changes in their blood pressure that we're worried they may decompensate very quickly, or in those who are at increased risk of hemorrhage. This is because it has a shorter half life and we have a medication that can reverse it if needed. This medication, because it washes out of your system is much quicker, only needs to be stopped four to six hours prior to delivery. We avoid some of those direct oral anti-coagulants such as apixaban and rivaroxaban in pregnancy and we avoid fondoparanox. Warfarin is generally avoided in this condition during the first trimester because it can have adverse effects for the baby. Systemic or catheter-directed clot buster or thrombolysis is usually not used unless the patient is very, very unstable and we're afraid that if we do not intervene immediately that the patient may pass. Real quickly about valvular disease. So in general, stenotic or narrow lesions are not as well tolerated as leaky or regurgitant lesions during pregnancy. The highest risk lesions include moderate to severe narrowing of the mitral valve, severe aortic valve narrowing, mechanical valves which I'll go into a little bit further, or if you have a bicuspid aortic valve with associated dilation of your aorta, that's another high-risk lesion. Just a quick word about prosthetic valves. So bioprosthetic valves are preferred over mechanical valves and young women who wish to become pregnant in the future. Maternal risk with a well-functioning bioprosthetic valve or a tissue valve is very low and they tolerate pregnancy very well. This is in contrast to mechanical valves. So mechanical valves are very high risk during pregnancy and this is mainly driven by the need for anti-coagulation. In fact, the chance of an event free pregnancy is only about 58% compared to 78% with a bioprosthetic valve. So mechanical valves pose a very high risk during pregnancy. So why does this happen? So again, pregnancy is a hypercoagulable state that results in increased risk of clotting off that valve or what we call valve thrombosis. There's a lower risk of valve thrombosis or clotting off that valve among patients who are on warfarin. And it's higher among those on low molecular weight heparin. Low molecular weight heparin is something that needs to be diligently monitored during pregnancy because the amount you need changes as your body changes with pregnancy. So if someone is on low molecular weight heparin, they need very, very close monitoring of their levels. No matter what, all anti-coagulation carries an increased risk of hemorrhagic complications and miscarriages. This is higher risk among warfarin. So warfarin is actually better for the valve but worse for the baby. And low molecular weight heparin is worse for the valve but better for the baby. So higher risk of miscarriage on warfarin is really dose related. So low dose or less than five milligrams is associated with a 13 to 19% risk of miscarriage versus high doses which is over a 30% risk of miscarriage. Lower risk of miscarriage occurs with low molecular weight heparin ranging from about 9 to 12%. The real risk with warfarin during the first trimester is it is associated with embryopathies or birth defects and or fetopathies or fetal death in a dose dependent manner. So low dose is actually pretty low risk. So your low dose is associated with a 0.45 or 0.9 risk of birth defects and about 0.7 to 2% risk of photopathy. Higher doses have a prohibitive risk of greater than 10% of both of these conditions. Low molecular weight heparin and heparin actually do not cross the placenta and are not associated with embryopathies. There's rare photopathies or loss of baby reported with heparin but not with low molecular weight heparin. So this is the schema that we use to determine how do we manage anticoagulation for these mechanical valves in pregnancy and it boils down to if during the first trimester you're on low dose heparin meaning less than five milligrams or five milligrams daily then you stay on that warfarin throughout pregnancy until right before delivery when you switch over to unfractionated heparin. If however you're one of those patients who are on higher dose of warfarin so over five milligrams then the goal is to switch over to low molecular weight heparin during the first trimester and then switch back to warfarin during the second and third trimesters. Warfarin is safer during the second and third trimesters because organogenesis or the development of the baby's organs is already complete so it's much lower risk to the baby at that time. Anytime you're switching between anticoagulation regimens it needs to be done in the hospital so we can make sure you're therapeutic before you leave. Now I know I covered a lot so let's just go over some major take home points. So maternal cardiovascular disease is the leading cause of death during pregnancy in the western world and women with known cardiovascular disease preconception counseling and close follow-up during pregnancy is needed. The hemodynamic changes that occur with gestation increase the risk of clotting and make certain valvular conditions worse so like your mitral stenosis and your aortic stenosis. Proper blood pressure control is very important for both the health of the mother and the fetus. Warfarin needs to be carefully monitored and therapy must be tailored to the individual and their underlying condition. Thank you so much.