Michelle Zikusoka, MD, FACC, Austin Heart Cardiologist, presents the latest on Women & Heart Disease.
today, my topic is a pregnancy and cardiovascular considerations. My goals are thio Recognize physiological changes that occur during pregnancy to identify risk factors for adverse maternal and fetal outcomes, to manage cardiac conditions during pregnancy and to review medication safety in pregnancy. I have no disclosures, So cardiovascular disease is the primary cause of pregnancy mortality in the United States. Advancing maternal age as well as pre existing co morbid conditions have contributed to the increased rates of maternal mortality. Right. A study by the World Health Organization noted that the United States lags behind other well resourced nations on maternal mortality. You can see here in this graph that the United States has ah mortality rate of about 14 maternal deaths per 100,000 live deaths, a ZA compared to our neighbors above. In Canada, we have twice the maternal mortality rate. Unfortunately, the United States is one of only a few countries with an increase in mortality rate since 1990. The question maybe, why considering all the resource is, But a number of these signals point towards racial disparities. Socio economic disparities are morbid obesity pandemic and the existence of metabolic syndrome presenting earlier and in women of childbearing age, to name a few. Furthermore, there are more women who are born with congenital heart disease that air surviving to childbearing age. So the conditions I would like to cover I'll cover most of these include hypertensive disorders, dislike, anemia, myocardial infarction, cardiomyopathy, arrhythmia, trombone, bolic disease, congenital heart disease, valuer disease, aortic disease and cerebral vascular disease. Given the time limitations, I think it would only do justice to congenital heart disease and valvular disease to present that as a separate talk. So I hope to return with a part two to expand on those very highly specialized cardiac conditions and pregnancy. So importantly is pre pregnancy counseling. Of course, cardiovascular disease does not preclude pregnancy, but it does, of course, impose an increased risk to mother and beat us. Women with cardiovascular disease should most certainly be counseled on both the maternal and fetal risks before conceiving. Unfortunately, we may not always reach patients preconception, but if there is that opportunity, um, it should be pursued. Preconception counseling is critical, and part of that is a detailed past medical history and, of course, a very detailed obstetrics history, including, um, any preterm labor and any complications of labor, including pre eclampsia. Furthermore, the preconception counseling is an opportunity to review medications. There are certain medications that are contraindicated in pregnancy, and it would be prudent to review those medications and change as appropriately in the preconception stage. So some good medical conditions are certainly high risk and completely prohibitive with regards to pursuing pregnancy. Those include pulmonary arterial hypertension, ventricular dysfunction with a left ventricular ejection fraction of less than 40%. Perry partum cardiomyopathy in the past, any degree of left sided heart obstruction that includes mitral and aortic stenosis, as well as hypertrophic obstructive cardiomyopathy. Many native severe co optation. Furthermore, aortic disease, including aortic dilation of greater than 50 mL. Sorry millimeters in aortic disease associated with a bicuspid aortic valve. Also in Marfan syndrome. With New York dilated greater than 45 millimeters, these patients should most certainly avoid pregnancy, given the risk. So the pre pregnancy counseling can offer an opportunity to create a cardio obstetrics team. Of course, that UPS includes a specialist in obstetrics, gynecology and refer maternal fetal medicine, but it also offers an opportunity for anesthesiology to weigh in genetics and if applicable, and of course, cardiology. Should there be any cardiovascular concerns? This is an opportunity for shared decision making. That way, the mother can make an informed decision with regards to their potential risk and outcomes at every stage of the pregnancy and postpartum process. This may also help inform timing and motive delivery. So again the list of cardiac conditions and pregnancy. I'd like to first start off with hypertensive disorders. I apologize. I'm going to start off with doing some basic review of cardiovascular physiology and pregnancy during the time of pregnancy. There are multiple adaptations to meet the increased metabolic demands off the mother and fetus to ensure adequate euro placental circulation for optimal fetal growth and development. Here is a graph noting the multiple human dynamic changes that occur in pregnancy. On the X axis, we have the timeline of pregnancy from preconception too early postpartum on the y axis, there's a percent angina given him a dynamic parameter. Firstly, with regards to blood pressure, there is generally a decrease within the first 6 to 8 weeks of gestation and meet our Children. Pressures tend to increase during the third trimester on return thio preconception levels postpartum. Secondly, there is an increase in heart rate. Generally, there is a 25% increase in from baseline preconception heart rate. Yeah. Also noted, there is as a change in systemic vascular resistance and this decrease in systemic vascular resistance can occur as early as five weeks. And if you look at the curve, the systemic vascular resistance will get quite low with a nature at about the early third trimester and slowly increase as we go towards late third trimester and towards early postpartum. The plasma volume also increases in pregnancy. Um, this is related to increased levels of vasopressin, um, and fluid retention. Um, this will cause a physiological media Thebes benefit of having this physiologic anemia is that there is a reduced reduction in resistance to flow, and it facilitates adequate potential profusion. Yeah. Lastly, the cardiac output will have changes during pregnancy. The sharpest rise in cardiac output is in the beginning of the first trimester. Then there's a continued increase over the course of the second trimester by 24 weeks. Increasing cardiac output can be as high as 45% above baseline from the non pregnant cardiac output, and when it comes to twin pregnancies, there is at least a further 20% increase in cardiac output. Studies measuring cardiac output have noted that the highest measurements are when the patient is in the left lateral decugis and the lowest measurements of cardiac output are expectedly when the patient is supine when the patient is supine. This is when there is compression of the I V C and therefore less pre load to contribute to the cardiac output. Yeah, yeah. So the challenges with pregnancy is that many of the symptoms of pregnancy overlap some of the symptoms of cardiovascular disease. Um, those symptoms include Disney on exertion, increased fatigue, palpitations as well as gestational oedema. In fact, gestational oedema is found in up to 80% of healthy pregnant women. Again, many of these symptoms air perfectly normal. But if there is presence of angina, resting, dystopia, paroxysmal, nocturnal dysthymia or any sustained arrhythmias, they most certainly warrant further diagnostic work up. So importantly is the cardiovascular examination and pregnancy. So normal findings include brisk created up strokes. Ah, mildly elevated jugular venous pressure. Ah, systolic murmur. At the left sternal border, you may hear a s three gallup related to the increase in pre load conditions. Peter Ledezma, as I mentioned earlier, as well as varicose veins focusing on that systolic murmur. Almost all pregnant women will develop physiologic murmurs. This is typically a soft mid systolic murmur heard along the left sternal border, and again it's detected in up to 90% of pregnancies. And the presence of this murmur and pregnancy is due to increased flow through the right and left ventricular outflow tract again related to the increase in cardiac output and circulatory volume and pregnancy. These murmurs tend to be one out of 6 to 2 out of six and intensity and they're not. They're they're also non radiating. Thes murmurs can be picked up as early as 10 to 12 weeks of gestation. So what is not normal on a cardiovascular examination of a pregnant woman are Rawls on lung examination, a diastolic murmur which may possibly be in indicative of aortic insufficiency. The whole assed olic murmur, which may point to either try custody or mitral valve challenges. Continuous murmur, a fixed split as to which may be telling of pulmonary arterial pressures as well as an s for suggestive of a decrease in compliance in the pregnant heart. Yeah, so as we go through the cardiac conditions, I'll first discuss hypertensive disorders of pregnancy. They're quite common and 912 per 10,000 delivery hospitalizations are related to hypertensive disorders of pregnancy. Oh, so here is a graphic Thio note before main categories of hypertensive disorders of pregnancy. Pre eclampsia, coupled with eclampsia, is new onset of hypertension with a value of 140 40/90 systolic Lee. This is diagnosed after the 20th week of gestation. It is also associated with significant protein, urea or other end organ damage. Pretoria being defined as a you're in a spot urine protein to Kratie ratio greater than 0.3 Other signs of end organ damage can include uh, elevated liver function. Testing could be signs of pulmonary oedema, also low platelets and hemolytic anemia. 1 may recall the health syndrome that's on the spectrum of this eclampsia preeclampsia, and the difference between preeclampsia and eclampsia is the presence of a seizure. The next disorder is gestational hypertension. This is diagnosed after 20 weeks of gestation. Three important point is that there is no evidence of protein area or other end organ signs again. The threshold is a new onset of hypertension, of a systolic value of greater than 1 40 diastolic greater than 90. Also, of course, there can be the presence of chronic hypertension and the presence of chronic hypertension. Again, the line of demarcation is whether or not it occurs, or it's noted. Ah, prior to 20 weeks gestation again, 1 40/90. Uh, lastly, there is chronic hypertension with superimposed pre eclampsia, and this can certainly occur in our chronic hypertensive patients. And again, this is where pre pregnancy counseling and early intervention and surveillance during the early trimesters come into play. Having a diagnosis of chronic hypertension will certainly predisposes. You will put you put you one at a far increased risk off pre eclampsia. So with regards to management, of course, the goals are to reduce maternal heart failure, myocardial ischemia, stroke or renal disease. The challenge is that there is no clear consensus on the optimal blood pressure threshold for initiation of antihypertensive treatment or to the target blood pressure for women who do not have significantly elevated blood pressure. Uh, there have been multiple studies that have been basically equivocal with regards to what that threshold is. We do at least know that we define pregnancy of hypertension 1 40/90 and then severe pregnancy of hypertension 1 60 with the diastolic over 110. And that would, um, that that threshold would lead Thio more aggressive interventions with regards. Teoh Medical management. So in our arsenal of medications include beta blockers. Libido well tends to be favored calcium channel blockers. My feta Penis favored. There is hydrology scene and with some use. There's also metal dopa, just like in hypertension. In nonpregnant individuals, lifestyle behavior modifications are always emphasized. They include diet, exercise and smoking. Cessation on studies have, in fact shown that exercise during pregnancy can improve vascular function and actually prevent create Plame's CIA. So this is a graphic of specifics of management of hypertensive disorders focusing first on the threshold. Again, it's greater than 1 60 over 110 millimeters of mercury. If the patient is below that threshold, standard oral therapy again will battle on my feet, a peen achieving a range of 1 40 to 1 50 over 90 to 100. That's a typo Sorry through the concern with decreasing it to more normal levels is possibility of challenges with perfusion of the placenta. Hence the controversy with regards to what the true treatment goal is with hypertension in pregnancy. So if the blood pressure is not controlled on those medications, hydropower thigh aside, is a great second line agent and, of course, theme. Mother and child should most certainly have frequent assessments. If you were on the spectrum of severe hypertension that patients should be admitted to the hospital for maternal fetal monitoring, the first line is ideal. A beta law, also ivy hydraulic seen if there's no I V access. A short acting on nifedipine is also a futility. Intravenous magnesium is also administered to prevent seizures and preeclampsia with severe features. Another drug is also intravenous nitroglycerin. This is particularly used when pulmonary oedema is present in the setting of preeclampsia. The nitro glycerin is an excellent medication to reduce pre load and therefore help with efforts of decreasing that pulmonary oedema. So postpartum follow up is very critical patient surveillance over the first 1 to 2 weeks. Um, it's noted that severe hypertension, our superimposed preeclampsia can still occur in the post partum period up to six weeks. Postpartum pull. So. Medication, of course, should be adjusted for a reasonable blood pressure goals and for women who continue tohave persistent hypertension for anywhere between 6 to 3 months postpartum, they should continue on with treatment of hypertension for the American College of Cardiology and A J guidelines moving on to hypercholesterolemia and pregnancy so physiologically and pregnancy the total cholesterol, triglycerides and HDL will steadily rise. Um, postpartum. These levels will decline over the next three months postpartum to pre pregnancy levels. Ideally, one is already screened for dislike Kadhimiyah. The screening should usually happen at least by the age of 20. Um, Thio identify any degree of disability. Mick challenges. And so here is a graphic noting how the pre hyper the pre pregnancy levels of of the lipids rise over the course of the pregnancy and then quickly fall down to pre pregnancy levels without intervention. Oh, it's important to note that statins or contra indicated and pregnancy they are to Radha genic. Um, this is again emphasizing the importance of pre pregnancy counseling. If your patient is on a statin and considering pregnancy, they should be counseled to stop the Staten at least 1 to 2 months prior to conception. So special considerations, of course, include familial hypercholesterolemia. There's an increased risk of pre eclampsia and gestational diabetes in those with Turkish ride levels greater than 250 mg per deciliter. If these levels are greater than 500 there's an increased risk of pancreatitis. These patients would benefit from the use of omega three fatty acids, with or without a vibrate, but those should be started after the second trimester. Sorry after the first trimester during the second. Yeah, those with familial hypercholesterolemia again. Those should not be on statins there. Terata genic bios Equestrians are an option. Those air medications that do not have any systemic circulation and can be used to control lipids during pregnancy. Next moving on to escape Mick Heart disease and pregnancy, a rare but potentially fatal condition and the risk of acute myocardial infarction is actually 3 to 4 times higher in pregnant women compared to their non pregnant counterparts. Although there is the possibility of the presence of atherosclerosis being the mechanism of disease, there are pregnancy related challenges such a spontaneous coronary artery dissection or myocardial infarction without constructive coronary disease. The third trimester and postpartum are the highest risk periods. Here is a graphic of the three main mechanisms of ischemic disease in pregnancy. Again spontaneous coronary artery dissection, athletic erotic disease, and Monica, the myocardial infarction with non obstructive coronary artery disease. That phenomenon is typically related to visa spasm, microvascular dysfunction and the creation of a supply demand mismatch. Given the hyper qua global state of pregnancy, there also is possibility the possibility of thrombosis within a normal coronary artery. But one thing to not forget in pregnancy is the possibility of Takasu bow or stress cardiomyopathy as a contributor to ischemic heart disease. So with acute coronary arteries disease um sorry coronary artery syndrome, it's important to recognize that the risk does not decrease after birth that actually carries on for about six weeks. Postpartum, of course, with stem e Standard of care is coronary angiography with timely profusion utilizing protocols to minimize fetal radiation exposure with lead shielding. Um, if coronary angiography is not available from politics were used but noting the increased risk of maternal hemorrhage in the setting of a non S T segment elevation myocardial infarction, all unstable patients should be referred to coronary angiography. Those who are low risk may be considered for conservative management as a part of the acute coronary syndrome management theme. The cornerstone is the use of anti coagulation, both in fractionated happen and low molecular weight. Heparin are safe in pregnancy. Um, with regards to intervention with per Catania's coronary intervention. Um, pregnant women were generally excluded from trials, so they're scarce evidence in this population. But low dose aspirin post intervention is considered safe throughout pregnancy, and clopidogrel can be used with the short, the shortest duration possible. Other agents, such as taika Galore and Cross the Girl, have not been studied, so they should therefore be avoided. Spontaneous coronary artery dissection generally involves conservative management. It's diagnosed to be a cardiac catheterization. Typically, um, perky titties. Intervention with something is typically not pursued. Uh, this is because of the nature of spontaneous dissection. Their radio forces related to balloon inflation with an area of obstruction and as well as extend expansion, can actually brought in that dissection worsen conditions. So PC I should only be performed in patients with left main coronary dissection. He would dynamic instability, recurrent chest pain or ongoing ischemia. So in women who have had a scheme IQ, heart disease and pregnancy. Um, those with pre I'm sorry. Those with pre pre pregnancy coronary disease should know that their increased risk of coronary ischemic complications is about 10%. Um, any of those with prior history of dissection left ventricular dysfunction or residual de schema are often are sorry, also at increased risk. And those patients should generally be heavily counseled with regards to any future pregnancies in their cardiovascular risk. Moving on to cardio myopathy and pregnancy. Um, this diagnosis is challenging with a focus on dilated cardiomyopathy as well as Perry. Pardon cardiomyopathy. They may present with the same spectrum of path of physiology, but the key input is the timing of that diagnosis. So with Perry partum cardiomyopathy, it's in about 1 to 15,000 live births. Important to note that new onset cardiomyopathy to define it as Perry partum cardiomyopathy is within one month of delivery or up to five months postpartum. Outside of those bounds, it is not Perry pardon cardiomyopathy, but up other ideology. So it is important if one is diagnosed with Perry, pardon cardiomyopathy within those bounds of one month pre delivery or five months post. One must exclude any other identifiable ideologies, including thyroid disease, HIV, extensive alcohol or drug abuse and possibly Jinan um, genetics, if possible. So it's generally defined as left ventricular ejection fraction less than 45%. And it is most certainly a significant cause of maternal morbidity and mortality. Yeah, this is a graphic of the variable risk factors that can contribute to Harry. Pardon cardiomyopathy. Um, smoking, hypertension, malnutrition, cocaine abuse, African and ancestry. Socioeconomic status has also been contributory to risk of Perry, part of cardiomyopathy, obesity, genetics, the presence of preeclampsia, prolonged total Isis, Extreme ages of reproduction, high parody and high gravity as well as twin pregnancy, are risk factors where the presence of Perry partum cardiomyopathy. So when it comes to Perry, part of cardiomyopathy prognosis is strongly linked to the ejection fraction of the left ventricle. At presentation, um, extremes of management of Perry Partum cardiomyopathy include heart transplantation, left ventricular assist device, Andi Association with death. Those generally occur in women whose ejection fraction is less than 30%. The treatment of patients with Perry Pardon cardiomyopathy follows the American College of Cardiology and American Heart Association Standard guidelines for management, which include volume reduction afterward. Reduction, arrhythmia control and anti coagulation as necessary. It is important to note that medications such as a Sinha, bitters and a ARBs as well a spironolactone are contraindicated in pregnancy as traditions cold. With regards to this Perry pardon cardiomyopathy, a studies have noted that the recovery of the left ejection fraction occurs almost exclusively within the first six months. Postpartum Thereafter. It is not likely that there will be much recovery of the ejection fraction. Oh so possible ideologies. There are some theories. Three. Challenge with Perry partum cardiomyopathy. The incidents is incredibly rare, and it's quite challenging to study. But animal models have suggested that prolactin production and excess can lead to Perry partum cardiomyopathy specifically to counter Act that there is a drug called Roma Christine. It can suppress prolactin production and has been associated with improvement in left ventricular systolic function in models with Perry Pardon cardiomyopathy. We in the United States do not utilize Programa Christine, but the and Europe they do use this as an adjunct therapy, uh, along with the standard cardiomyopathy medications in women with Perry, Pardon cardiomyopathy, right. Another theory for the development of Perry, part of cardiomyopathy is autoimmune disorder. Um, this was noted. It was noted that there were high tigers of anti excuse me auto antibodies against cardiac tissue in the serum of patients with Perry partum cardiomyopathy, as opposed to those without. Nevertheless, counseling is critical in patients with Perry partum cardiomyopathy, significant increased risk of morbidity and mortality with future pregnancies and ideally, um, pregnancy. It should be completely discouraged in this population. Yeah, briefly discussing arrhythmia and pregnancy, super ventricular or particular, and ideology very commonly in modern women, we may see ectopic beats, premature Rachel contractions or premature ventricular contractions a swell as non sustained women. There was a study that noted that this may be prevalent and is in as many as 50% of pregnant women. Sustained arrhythmias, though, occur in 0.2 to 0.3% of pregnancies, and their most typically, um, increasing an incidents in the third trimester. Super ventricular tachycardia is the more prevalent sustained technique Arctic a tech cardiac arrhythmia as opposed to ventricular tachycardia, and the management is the same as the nonpregnant population. First line is carotid massage and Val Salva maneuvers thief. First line pharmacological therapy is Dennis ing the next choices rapid mill. But that is on Lee after the second sorry only after the first trimester of pregnancy, and only in acute circumstances. Thereafter, patients are typically managed with low dose beta blockers. Those were effective for both premature atrial and ventricular contractions or any form of tacky arrhythmias in pregnancy. Cardioversion is, uh, is, uh, of course, utilized in pregnancy. It is actually safe in pregnancy, but important precautions should take place. Um, one should note that the hyper remick uterine muscle, as well as the amniotic fluid, are very excellent conductors of electricity. Therefore, pad placement is critical. The anterior posterior positioning is recommended avoiding the interior and a pickle positioning of pads. The reason for this is because of the proximity, of course, the large gravity uterus and knowing that the uterine muscle and the amniotic fluid are high conductors of electricity. The goal is to minimize fetal risk, so therefore, positioning your pads, interior and posterior would minimize any degree of risk to the fetus, and they'll receive a minimum amount of current. Next topic is deep venous thrombosis and pulmonary embolism and pregnancy. This is 4 to 5 times more common during pregnancy. The absolute risk remains low, though, at 0.3% for Trumble embolism and 1.2% for DVT. And the majority of thes throng biotic events occur in the post partum period. So when it comes to DVT, it's typically proximal in the Iliac Aurilia ephemeral distribution. Um, if there is a high index of suspicion and the ultrasound is initially negative, serial ultra sonography should be pursued in about 3 to 7 days or consideration of Magnetic resident with regards to the diagnosis of pulmonary embolism. It's certainly a challenge because of some of the normal physiological changes of pregnancy and typical complaints of shortness of breath that may occur as pregnancy progresses. Di dimmer, um, can be tested, but it typically increases with each trimester, so therefore, it has a very low specificity. The next option is imaging V. Q scan versus contrast CT. There may be some degree of trepidation with pursuing contrast CT, but that actually offers less radiation exposure to mother and fetus and B Q scan. Yeah, it's important to remember that pregnancy is a hyper choir global state. Just by nature. There's an increased risk of traumatic events. 20% of which are arterial and 80% Venus during pregnancy. Physiologically, we have increased in bond villain brand factor factor eight plasminogen activator one and two. There's also a reduction in protein s, and there's also an increase in platelet aggregation caused by hyper proact anemia. Furthermore, increased hyper Koegel ability can occur in the setting of compressive, and he would dynamic venous Stasis. Recall. I mentioned that there is some degree of Stasis, especially with compression off the I V C by the gravity uterus, with the mother in a supine position. The left lateral to Cuba's position is the most ideal positioning, particularly for sleep. Yeah, right on, of course, just by nature of delivery. There's endothelial trauma, so that in turn off further increases the hyper questionable state of pregnancy. So management generally is with, um, fractionated Hepburn. Again, it is safe and pregnancy. It's recommended for acute P E or DVT. In stable patients, you can use low molecular weight heparin. It's actually preferred over an fractionated Hepburn. Unfortunately, 4% of pregnant patients where the Venus rumble embolism have can experience a cardiac arrest. In these cases, through Humble Isis is recommended, but of course, noting the risks increased risk of maternal hemorrhage. Obviously, filters, although rarely used, can be used if anticoagulants shin is completely contraindicated or if it has failed. So here is an adapted graphic from the A. J Guidelines for the care of the Pregnant Patient. Um, there are multiple options over the course of pregnancy for anti coagulation. Um, when it comes to warfarin, it is to allergenic. It does cross the placenta. It's probably okay in breastfeeding with regards to initiation, initiation is usually no sooner than the first trimester. No sort of in the second trimester of pregnancy. Um, that between time, though, the patient can be bridged with low molecular weight. Happen? Um, indications may include P e D V T, of course, valvular disease and the therapeutic doses of therapeutic dose ing for I and R should be, according to the initial diagnosis, be it D V T P E or mechanical valve. Um, it is important to note that the patient should have no more than 5 mg per day of warfarin, increasing doses of warfarin, increased strategy, ethnicity. If you do have a patient that cannot maintain therapeutic, I in our with less than 5 mg a day of warfarin. They will likely need to use low molecular weight heparin over the duration of their pregnancy to minimize risk to the fetus. Next, our direct thrombin inhibitors. This includes the bigger Tran Um, there is limited data insufficient data As far as to indigenous city, it has been noted Thio cross the placenta. It should be avoided in breastfeeding should be avoided during pregnancy. One can take it during postpartum as long as you're not black. Breast feeding on the dozing is the standard of 150 mg the i d. With regards thio Anti factor 10 A inhibitors. Those include, um el acquis. Um, there is not enough data with regards to try indigenous ity, but it is known to cross the placenta. It should be avoided in pregnancy. It should be avoided in breastfeeding, but it can be used postpartum as long as the mother is not breastfeeding with slightly higher doses and standard with eloquence of 10 mg and river rocks. Even a 15 mg b i d. Our other um interventions include on fractionated happen. This is known to not be throughout hygienic. It does not cross the placenta. It is likely okay in breastfeeding, and this can be used for DVT t e mechanical valve bridging when one is anticipating delivery and, of course, atrial fibrillation or flatter um, it can also be used postpartum and standard therapeutic doses. Lastly, low, low molecular weight heparin not to write a genic does not cross the placenta. Probably okay with breastfeeding. Um, typical anti part of indications, including P E D. V T. A fib, a flatter and, of course, post postpartum. It can be used on DTIC pickle therapeutic dose ing of 1 mg per kilogram to 12 oh so Segway into cardiovascular medications in pregnancy, there are those that are safe, and those that are absolutely contraindicated safe ones include hydrology, method dopa, beta blockers, calcium channel blockers, D Jackson, a dentist see Burkina mydd, light, a cane, furosemide and aspirin. Absolutely. Contraindicated medications in pregnancy include amiodarone. The concerns, due to the long half life as well as potential uh, abnormalities of thyroid for the fetus and feet, fetal bradycardia, ace inhibitors and a ARBs has mentioned earlier are too ratty genic. They can lead to neonatal renal failure. Olive hydra MEOWS, hypertension, respiratory distress, limb defects. Patent doctor sartorius, ISS and also feel death. Nitra Press side also is contra indicated there are concerns for elevated cyanide levels in the fetus, from a lack tone as a never toxic agent for the fetus and against statins as a threat. Hygienic agent. Aspirin is a medication that's Austin question. With regards to its utility and pregnancy, studies have shown that aspirin should be considered in those patients again reemphasizing the importance of pre pre pregnancy counseling. But in those patients with chronic hypertension, those with pre term eclampsia in the past preterm birth at less than 34 weeks gestation, diabetes or a known P fo thes congenitally be started in the late first trimester, and they are safe and non trata genic Um, a great tool. Um, that could be used to kind of assess cardiovascular medications is, uh, the infant risk app. Um, I highly recommend downloading it onto your smartphones. I mention this because, um, it's not very often that one encounters cardiovascular challenges with pregnancy, and, um, this could be a great resource to kind of have your right at your fingertips. If you have a question about drugs, whether or not drugs could be should be discontinued whether or not they're safe, in which trimester it also notes safety and breastfeeding and thereafter postpartum. So this is a great tool to use. Have it right at your fingertips. Given the frequency that we encounter patients with cardiovascular complications of pregnancy, we often have thio quickly. Reach for resource is and this is obviously a quick and accessible resource for this. Oh, so we've gone through a number of different cardiovascular conditions and pregnancy. I did omit congenital heart disease, valvular heart disease, the order disease and cerebral vascular disease, particularly just due to time constraints. I feel that congenital heart disease and valvular disease really truly deserve a talk all their own, given the complexities of pathology and anatomy and different considerations during labor, um, anesthetics and the pre and postpartum course. So I hope to return for a part two at one point in time. Eso there go my references and I'd like to open the discussion up for any questions. Hey, this is a stand Wang great presentation. I really enjoyed that. Thank you. Have a quick question for you. I have a lady with Mark fans and an aortic diameter of 4.7 centimeters. She against kind of all of our recommendations, went ahead and got pregnant and had a child successfully. No complications. Okay. Do not want to have a second child. How would you counsel her? I would firmly counsel them again with regards to the risks. I mean, depending on the timing of this next child. Certainly Shell require serial scans for her aorta anyway, at Baseline, given her condition. But she firmly needs counseling with regards to how much she's putting herself and her child at risk for any future pregnancies. Um, and to some degree, um, it, of course, the onus is on the mother with regards to making an informed decision. But I would heavily council against any further pregnancies. And she's very fortunate to have survived. Such despite her parameters being beyond goal. Yeah, that's similar to what I told her, but she's emboldened by her successful pregnancy. And I told me that wasn't necessarily make you're more likely to succeed in this one. Yeah, that's a really tough one. I mean, you did your best as faras give making her She had her an informed decision and the truth is she's an adult, and unfortunately, she does have those complications. She'll have to cross those bridges if and when we get there. But as long as we as clinicians stand firm with regards to our counseling at risk and, of course, always documenting such so that there are any complications in the future should there be any clinical challenges Um, that's honestly, unfortunately, the best Weaken Dio. Thanks. Well, I thank you all for joining me so early this morning. And I hope you all have a great day. And I hope to return at a later point in time for part two to focus on congenital heart disease and bowels. Thank you very much. Justus Faras contact information. I've left my office number as well as my personal cell phone number. Happy to have conversations, a received text, anything like that to engage in conversations on a cardio theatrics and trying to optimize the care for this very, very special patient population. Thank you very much and have a great day like