128. Cardio-Obstetrics: Hypertensive Disorders of Pregnancy with Dr. Jennifer Lewey

CardioNerds (Amit Goyal and Daniel Ambinder), Cardio-OB series co-chair and University of Texas Southwestern Cardiology Fellow, Dr. Sonia Shah, and episode lead and Columbia University Cardiology Fellow Dr. Ersilia DeFilippis discuss hypertensive disorders of pregnancy (HDP) with Dr. Jennifer Lewey from the University of Pennsylvania.

In this episode, we cover chronic hypertension, gestational hypertension, and pre-eclampsia—all of which encompass HDP and complicate approximately 5-10% of all pregnancies. We also review risk factors for HDP, diagnostic criteria, peripartum and postpartum management, and much more! Be sure to tune in to hear Dr. Lewey discuss the future impact of HDP on cardiovascular disease for women later in life and strategies that can help improve care.

Finally Dr. DeFilippis shares her perspectives from her ACC.org FIT Section article titled “Shattering the Glass” including strategies to shattering the glass and tackling imposter syndrome in improving the representation of women in medicine.

Audio editing by CardioNerds Academy InternLeticia Helms.

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Pearls

  1. To make a diagnosis of HDP, blood pressure should be measured on at least 2 occasions at least 4 hours apart.
  2. Hypertension diagnosed before 20 weeks gestation is considered chronic hypertension whereas hypertension after 20 weeks is categorized as gestational hypertension.
  3. Always check for warning signs for pre-eclampsia!
  4. One of the key treatments for pre-eclampsia is delivery but pre-eclampsia can occur still in the postpartum period.
  5. Aspirin use in pregnancy during second and third trimesters can reduce the risk of pre-eclampsia among women at risk.

Quotables

“Ideally a lot of these conditions come down to prevention and addressing potential cardio-obstetrics issues before they reach the cardio-obstetrics specialist.”

“Blood pressure can continue to be elevated even after delivery.”

“Pregnancy complications not only increase cardiovascular risk in the middle age population but also in the postmenopausal population.”

“Women feel so relieved when they know that their care team is dedicated to taking care of women with cardiovascular disease when they are pregnant.”

Show notes

  1. Why should CardionNrds learn and know about hypertensive disorders of pregnancy?

Hypertensive disorders of pregnancy (HDP) complicate about 5-10% of all pregnancies. HDP is a term that encompasses chronic hypertension, gestational hypertension, pre-eclampsia, and pre-eclampsia superimposed on chronic hypertension. Women with history of HDP are at increased risk for stroke, ischemic heart disease, and cardiovascular death later in life. It is important to include obstetric history as part of our assessment of cardiovascular risk.

This obstetric history should include the number of pregnancies, history of gestational diabetes, gestational hypertension, history of pre-eclampsia as well as history of pre-term birth.

Following delivery, these women need close monitoring for development of chronic hypertension as well as primary prevention of cardiovascular disease.

2. How is gestational hypertension distinguished from chronic hypertension?

The key factor in distinguishing gestational hypertension from chronic hypertension is the timing of diagnosis. Before 20 weeks gestation, elevated blood pressure (defined as a reading > 140/90 on two occasions at least 4 hours apart) is considered chronic hypertension. After 20 weeks gestation, elevated blood pressures signify a pregnancy-induced process, namely gestational hypertension or pre-eclampsia if blood pressure elevation is severe enough or there is evidence of end-organ damage.

Blood pressure is often lower in the 1st and 2nd trimesters due to lower systemic vascular resistance. We think the process of gestational hypertension and pre-eclampsia result from how spiral arteries implant in the uterus. There are a whole host of local factors that lead to an increase in blood pressure later on in pregnancy.

3. What are warning signs of pre-eclampsia?

Pre-eclampsia is diagnosed in the setting of high blood pressure, usually after 20 weeks, in the setting of proteinuria or end-organ dysfunction. End-organ dysfunction most commonly includes thrombocytopenia, transaminitis, right upper quadrant pain, headaches, pulmonary edema, and symptoms and signs that are not explained by other causes. Notably, blood pressure readings greater than > 160/110 mm Hg are sufficient for the diagnosis in the absence of other findings.

4. What are risk factors for pre-eclampsia or pre-eclampsia superimposed on chronic hypertension?

Risk factors for pre-eclampsia include a personal or family history of pre-eclampsia in prior pregnancies, chronic hypertension, older age, multiple gestation, obesity, and Black race.

5. When do we start treatment for hypertension during pregnancy?

For women who are newly diagnosed with hypertension during pregnancy, the threshold to begin treatment is 160 mm systolic and 110 mm diastolic. The caveat to this is for women with known cardiovascular disease or other comorbidities, a lower blood pressure goal should be targeted closer to 120-130 mm Hg systolic over 80 mm diastolic. Typically, a higher blood pressure is tolerated in order to avoid uteroplacental hypoperfusion which can impact the growth of the baby.

The CHIPS randomized trial was published in the NEJM in 2015 and compared less tight control (targeting diastolic blood pressure of 100 mm Hg) or tight control (targeting diastolic blood pressure of 85 mm Hg). Although tight control decreased the rate of severe maternal HTN, there was no significant difference in the risk of pregnancy loss or overall maternal complications.

  1. How can we modify risk in women with hypertension during pregnancy?

Low dose aspirin use (81 mg daily) in pregnancy during second and third trimesters can reduce the risk of pre-eclampsia among women at risk. The USPTF recommends the use of aspirin as preventative medication after 12 weeks of gestation in women at high risk for pre-eclampsia (Grade B). Risk factors that qualify someone as high risk include history of pre-eclampsia, multifetal gestation, chronic hypertension, type 1 or 2 diabetes, renal disease, and/or autoimmune disease. ACOG also recommends aspirin prophylaxis initiated between 12 and 28 weeks of gestation, optimally before 16 weeks and continued daily until delivery.

7. What is the best approach to anti-hypertensive medication use in pregnancy?

First line agents used during pregnancy for treatment of hypertension include labetalol and nifedipine. Hydralazine is a second-line agent that may be used. Although methyldopa classically appears on board exams, it is less effective and has side effects including depression and fatigue.

For women with a history of hypertension prior to pregnancy that is well-controlled on agents such as amlodipine or hydrochlorothiazide, these can be continued since limited evidence suggests they are safe although there is just less available evidence.

For women on angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or mineralocorticoid antagonists, these must be stopped given their teratogenic effects.

This table from a recent JACC review by Halpern et al summarizes nicely safety of antihypertensive medications in pregnancy and during breastfeeding.

8. How do we treat pre-eclampsia?

Treatment of pre-eclampsia depends on severity and gestational age. Management is primarily two-fold: 1) using intravenous medications such as labetalol and hydralazine to lower the blood pressure; 2) magnesium sulfate for seizure prophlaxis. Delivery may help resolve the symptoms of pre-eclampsia and may be considered following 37 weeks gestational age.

References

Halpern et al. Use of Medication for Cardiovascular Disease During Pregnancy: JACC State-of-the-Art Review. JACC 2019;73(4):457-476.

ACOG Committee Opinion. Low Dose Aspirin-Use During Pregnancy. July 2018.

Magee et al. Less-Tight versus Tight Control of Hypertension in Pregnancy. NEJM 2015;372:407-417.

Wang Y-X, Arvizu M, Rich-Edwards JW, et al. Hypertensive disorders of pregnancy and subsequent risk of premature mortality. J Am Coll Cardiol. 2021;77(10):1302-1312. doi.org/10.1016/j.jacc.2021.01.018.

Guest Profiles

Dr. Jennifer Lewey
Dr. Jennifer Lewey

Dr. Jennifer Lewey is an Assistant Professor at the  University of Pennsylvania, Director of Penn Women’s Cardiovascular Health Program, and Co-Director of the Pregnancy and Heart Disease Program.

Dr. Silia DeFilippis
Dr. Silia DeFilippis

Ersilia DeFilippis is a third-year general cardiology fellow at Columbia University Irving Medical Center in New York City. She will be beginning her fellowship in advanced heart failure and transplant cardiology next academic year at Columbia. Her research and clinical interest are in sex differences in advanced heart failure management and outcomes, racial disparities in heart failure outcomes, and cardio-obstetrics.

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126. Cardio-Obstetrics: Pregnancy and Aortic Disorders with Dr. Nupoor Narula

CardioNerd Amit Goyal, Cardio-OB series co-chair and University of Texas Southwestern Cardiology Fellow, Dr. Sonia Shah, and episode lead and Johns Hopkins University Cardiology Fellow, Dr. Anum Minhas, discuss pregnancy and aortic disorders with Dr. Nupoor Narula of Weill Cornell Medical College. Special introduction by Sukrit Narula.

In this episode we discuss the presentation and management of aortopathies during pregnancy. We begin by examining the pathophysiology of aortic disease during pregnancy, followed by a review of the heritable aortopathies and their risk of dissection. We then discuss preconception evaluation and antepartum care of women with aortopathies. We end with addressing management at the time of labor and delivery.

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Episode Abstract – Pregnancy and Aortic Disorders

In this episode we discuss the presentation and management of aortopathies during pregnancy. We begin by examining the pathophysiology of aortic disease during pregnancy, followed by a review of the heritable aortopathies and their risk of dissection. We then discuss preconception evaluation and antepartum care of women with aortopathies. We end with addressing management at the time of labor and delivery.

Pearls – Pregnancy and Aortic Disorders

1. Assessment of aortic root and ascending aortic measurements should be performed prior to conception in women with known aortopathies, connective tissue diseases with high risk for aortopathies, bicuspid aortic valve or familial thoracic aortic syndromes. Dimensions should always be verified with multi-modality imaging prior to decision-making.

2. It is important to recognize that the immediate postpartum period is a high risk period for aortic dissection in women with aortopathies.

3. Goal systolic blood pressure is < 120 mmHg and diastolic blood pressure is < 80 mmHg in women with aortopathies. This goal should be discussed with the patient’s obstetric provider during pregnancy, however, to ensure a blood pressure target is chosen that is appropriate for optimal maternal and fetal outcomes. Beta-blockers followed by calcium channel blockers should be used for these targets. Aldosterone receptor antagonists are contraindicated during pregnancy.

4. Per the 2018 ESC guidelines, during pregnancy, women with aortic pathology should have an echocardiogram performed every 12 weeks if low risk, and every month (4 weeks) if high risk.

5. Women with type A dissection during pregnancy should be evaluated for urgent Caesarean section and aortic surgery if the fetus is viable. Women with a stable type B dissection may be managed medically if stable. All decisions should be made in a multidisciplinary fashion with consultation with Maternal Fetal Medicine and Cardiothoracic Surgery.

Quotables – Pregnancy and Aortic Disorders

1. “First and foremost, we must verify our dimensions. I’ll say that again. We must verify our dimensions because nothing could have greater impact.”

2. “You know, our most important role is to provide transparency in pre-pregnancy risk counseling. We have to present the data that are available. We need to present the gaps in literature.  We need to present the possibility that in the right individual, we can proceed through pregnancy safely with close clinical and imaging monitoring and follow up in a multidisciplinary construct.

Show notes – Pregnancy and Aortic Disorders

  1. What is the risk of aortic dissection during pregnancy in Marfan syndrome?
    • Women who undergo pregnancy with prepartum counseling and close clinical and imaging follow-up usually maintain stability of aortic dimensions over time and risk of type A dissection appears low.
    • Type B dissection remains unpredictable.
    • Overall, the risk of aortic complications surrounding pregnancy remains eight-fold higher than in the non-pregnant state. The risk for dissection is higher with greater aortic root size, but there still remains a risk for dissection at diameters less than 40 mm.
    • Note, in the GenTAC registry (which included 184 women with Marfan’s Syndrome in whom pregnancy information was available), lack of knowledge of the underlying diagnosis of Marfan’s was not uncommon.
  1. What is the underlying pathophysiology behind increased risk for aortic dissection during pregnancy?
    • Pregnancy is associated with both hemodynamic changes and alterations in tissue architecture which may both increase the risk of exacerbating an underlying aortopathy syndrome.
    • Physiologic changes during pregnancy include increased stroke volume and heart rate, resulting in increased cardiac output, with concomitant decrease in the peripheral resistance, particularly in the second and third trimesters and immediate postpartum period (Review our Initial Episode in the Cardio-Ob Series for more details).
    • Pregnancy-associated morphologic and histochemical changes of the aortic wall also occur.
    • In women with Marfan syndrome, at baseline aortic tissue tends to be weaker and more prone to dilatation and dissection.
    • Animal studies also implicate oxytocin in increasing dissection risk, with a suggestion that withholding lactation or administration of an oxytocin receptor antagonist may reduce dissection risk.
  1. For patients with suspected or confirmed aortopathy or familial aortopathy syndromes, what evaluation is recommended prior to and during pregnancy?
    • Complete physical exam, including cardiac and vascular exams, should be performed, as well as review of personal and family medical/surgical history.
    • Echocardiogram should be performed to inform the safety of pregnancy.  Echocardiogram can be used to obtain aortic dimensions and identify any co-existing disease prior to conception.
    • Per the 2018 ESC guidelines, during pregnancy, women with aortic pathology should have echocardiogram performed every 12 weeks if low risk, and every month (4 weeks) if high risk.
    • Beta-blockers throughout pregnancy should be considered, along with fetal growth monitoring. 
    • While aldosterone receptor antagonists may normally be advised, these are contraindicated during pregnancy due to their teratogenic effects and should be withheld.
    • Collaboration with colleagues in Maternal Fetal Medicine for management decisions is critical.
  1. What are some specific syndromes related to aortic pathology and the risks of each of these conditions?
    • Marfan syndrome
      • AHA/ACC guidelines recommend consideration of elective aortic surgery prior to pregnancy if aortic root is > 4.0 cm.
      • The 2018 ESC guidelines advise against pregnancy for aortic root diameter > 4.5 cm.
      • The decision to intervene prophylactically during pregnancy is highly individualized and complex, and we must weight patient factors including gestational age and rapidity of growth while balancing risk/benefits to the fetus and mother. 
    • Ehlers-Danlos syndrome (EDS)
      • Vascular EDS patients are at high risk of arterial and uterine rupture, and the 2018 ESC Guidelines recommend against pregnancy. If after shared-decision making a patient decides to proceed with pregnancy, the patient should be cared for in a specialized center with a multi-disciplinary Cardio-Ob team.
    • Loeys-Dietz syndrome
      • There is limited data is available, and it is insufficient to make any clear recommendations regarding pregnancy. Most centers will generally approach prophylactic aortic root surgery in Loeys-Dietz syndrome similar to Marfan disease and consider elective repair at 4.0 to 4.5 cm.
      • More frequent intrapartum echocardiograms may be considered given some suggestion of increased risk of dilatation during pregnancy.
    • Turner Syndrome
      • There is a strong association with bicuspid aortic valve (present in 15-30% of patients). Generally, we consider elective surgery in patients with an aortic size index (ASI) (ascending aortic root size indexed to body surface area) of > 2.5 cm/m2 and that pregnancy should be avoided at this ASI cutoff. During pregnancy, prophylactic aortic surgery can be considered with a dilated aorta (> 2.5 cm/m2 or rapid enlargement > 3mm)
      • Many women with Turner syndrome require assisted reproductive therapy (ART) and assisted reproductive therapy may increase the risk of cardiovascular complications.
      • Imaging of the thoracic aorta and heart are recommended within two years prior to pregnancy or assisted reproductive therapy.
      • Imaging should be performed at least once per 20 weeks if there is no increased ASI or other cardiovascular risk factors (e.g., family history of dissection or sudden death, bicuspid aortic valve, coarctation, elongation of the transverse arch).
      • Imaging should be performed every 4-8 weeks for those with ASI > 2.0 cm/m2 or additional risk factors during pregnancy, and once during the first month after delivery. Subsequent imaging intervals depend on the severity of the aortic enlargement.
    • Bicuspid aortic valve (BAV)
      • Up to 50% of patients with BAV also have ascending aortic dilatation
      • ESC guidelines recommend elective aortic surgery if the ascending aorta is > 5.0 cm prior to pregnancy.
    • Familial Thoracic aortic aneurysms
      • Family history is present in 20% of patients.
      • A series in 53 women with ACTA2 mutations and total of 137 pregnancies showed 8 pregnancy-associated dissections (6 were type A) .
      • Evidence is limited, however, and no clear recommendations for pregnancy are available.
  1. What are some delivery considerations for women with aortopathies?
    • The overall goal is to decrease the cardiovascular stress of the delivery process, and risk for both the mother and baby need to be considered jointly with the Maternal Fetal Medicine team.
    • For Marfan Syndrome and aortic root between 4-4.5 cm, vaginal delivery with an expedited second stage and regional anesthesia is typically the preferred mode of delivery to avoid spikes in blood pressure.
    • For patients with vascular EDS, consider C-section at 35-37 weeks’ gestation. There is a similar recommendation for patients with Marfan syndrome and aortic root > 4.5 cm and Turner syndrome patients with ASI > 2.5 cm/m2.
    • For those with a type A dissection during pregnancy the approach depends on fetal viability. If viable, then urgent C-section and surgical aortic repair should be performed. If the fetus is currently non-viable, aortic repair is performed without delivery, acknowledging the high fetal risk in this context.
    • The approach to unstable type B dissection is as for type A dissections as above with C-section and aortic surgery if the fetus is viable or aortic surgery without deliver if the fetus is not viable at the time.  For stable type B dissection, medical therapy can be pursued.

References

Regitz-Zagrosek V et al. 2018 ESC Guidelines for the Management of Cardiovascular Diseases during Pregnancy: The Task Force for the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology. European Heart Journal. 2018;39(34):3165-3241. https://academic.oup.com/eurheartj/article/39/34/3165/5078465#186438440

Mehta et al. Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement from the American Heart Association. Circulation. 2020;141:e884–e903. https://www.ahajournals.org/doi/suppl/10.1161/CIR.0000000000000772

Guest Profiles

Dr. Nupoor Narula
Dr. Nupoor Narula

Dr. Nupoor Narula. Dr. Narula earned her medical degree from the Icahn School of Medicine at Mount Sinai, and graduated with Distinction in Research. She then went to the esteemed Mayo Clinic for Internal Medicine residency, followed by a Vascular Medicine fellowship at Mount Sinai Hospital and Cardiology Fellowship at New York Presbyterian Hospital – Weill Cornell Medical College. She has pursued basic and clinical research training in cardiovascular genetics and is currently completing her Masters in Clinical Epidemiology. Dr. Narula is also a superstar researcher and received grant funding for her research during her Fellowship by the Michael Wolk Heart Foundation and is currently a Fund for the Future Grant Kellen Scholar at Weill Cornell Medicine. She is studying aortopathies, such as Marfan syndrome, with special emphasis on pregnancy and dissection risk.

Dr. Anum Minhas
Dr. Anum Minhas

Dr. Anum Minhas went to medical school at Duke University. She had an interest in imaging and spent a year studying radiation dose estimation and radiation safety. She also developed a passion for clinical cardiology and subsequently went to the University of Michigan for internal medicine residency. Here she studied CT reconstruction for transcatheter aortic valve replacement, as well as the incidence of Takotsubo cardiomyopathy. Anum is a fourth year cardiology fellow at Johns Hopkins interested in cardio-OB. In fact, she has designed and is the inaugural Cardio-Obstetrics fellow at Hopkins. In her free time she enjoys drawing, reading, traveling, and spending time with friends and family.

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114. Cardio-Obstetrics: Pregnancy and Coronary Disease with Dr. Malissa Wood

CardioNerds Amit Goya and Daniel Ambinder, cardioobstetrics series co-chair Dr. Natalie Stokes, and episode lead Dr. Priya Kothapalli (University of Texas at Austin, Dell Medical School) discuss pregnancy and coronary artery disease with Dr. Malissa Wood, co-founder and co-director of the Corrigan Woman’s Heart Health center at Massachusetts General Hospital. They discuss the differential diagnosis of chest pain in the pregnant patient, the diagnostic approach and management of acute coronary syndromes in the patient population, and manifestations and management of SCAD in pregnancy. Episode introduction by Dr. Julie Power.

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Guest Profiles – Episode 114. Pregnancy Coronary Disease

Dr. Malissa Wood
Dr. Malissa Wood

Dr. Malissa Wood is a cardiologist at MGH, where she is one of the founders and co-director of the Corrigan Woman’s Heart Health center at MGH. She has authored two books “Smart at Heart” and “Thinfluence” and she’s made substantial contributions globally in promoting awareness of gender disparities in cardiovascular disease. She is the incoming chair elect for the ACC board of governors and current Governor of the Massachusetts ACC chapter, and is one of the leading experts in the world of Spontaneous Coronary Artery Dissection, or SCAD.

Dr. Priya Kothapalli
Dr. Priya Kothapalli

Dr. Priya Kothapalli is a second-year cardiology fellow at The University of Texas at Austin, Dell Medical School. Her clinical interests include endothelial dysfunction and vulnerable plaque. She looks forward to advanced training in interventional cardiology.

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