124. Cardio-Obstetrics: Pregnancy and Pulmonary Hypertension with Dr. Candice Silversides

CardioNerd (Amit Goyal), cardioobstetrics series co-chair Dr. Sonia Shah (FIT, UT Southwestern) and episode lead Dr. Kayle Shapero (FIT, UPMC) discuss pregnancy in patients with pulmonary hypertension with Dr. Candice Silversides, Associate Professor of Medicine and the Director of the Pregnancy and Heart Disease program and head of the Obstetric Medicine program at the University of Toronto.

Disclosures: None

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AbstractPearlsQuotablesNotesReferencesGuest ProfilesProduction Team


Episode Abstract

In this episode we discuss the important and challenging topic of pulmonary hypertension in pregnancy. We’ll start by discussing the prevalence of pulmonary hypertension in pregnancy, as well as the associated maternal morbidity and mortality associated with each WHO class. We will use a case to help us illustrate the appropriate workup for pulmonary hypertension patients and to help us broach the challenging topic of pregnancy termination. In this case we will further explore advanced management options including pulmonary vasodilators, anti-coagulation, and the use of mechanical support. Don’t miss this opportunity to hear Dr. Silversides’ share her wisdom on the importance of a multidisciplinary care team to plan both the delivery as well as post-partum care to help prevent adverse outcomes for both the mother and baby.

Pearls

  1. Pregnancy in pulmonary hypertension, regardless of the class, is considered high risk. Even women who appear hemodynamically stable at baseline can easily decompensate in pregnancy, and thus the overall mortality and morbidity are very high.
  2. Due to the high risk of maternal morbidity and mortality during pregnancy for women with pulmonary arterial hypertension, the option of termination of pregnancy should be discussed.
  3.  Multidisciplinary care teams are the key to achieving optimal pregnancy outcomes in these patients. It is critical to create a team of experts with experience in pulmonary hypertension and plan for constant communication over the course of pregnancy.
  4. Pulmonary vasodilators including CCBs, phosphodiesterase inhibitors, and prostacyclin analogues should be initiated early to mitigate adverse outcomes.
  5. The majority of the complications in pulmonary hypertension patients occur after delivery, and so having a clear and safe postpartum plan is critical to a positive outcome.

Quotables

  1. “We will someday identify the women who maternal morbidity and mortality is perhaps lower and we’ll be able to give a better, risk assessment. But we’re not quite there yet. And so currently, any woman who has pulmonary hypertension, true pulmonary hypertension in particular, pulmonary arterial hypertension, should be advised to avoid pregnancy.“ – Dr. Silversides
  2. “Women with PH can be falsely reassuring because they can walk in and look pretty good. And they’re young, you know, they’re not like the normal 70-year-old you might see on the ward. And so, you think they’re going to be okay, but they can spiral downward very quickly. So I do think you also have to have a very high, um, uh, level of. Uh, caution in these patients.“- Dr. Silversides on assessing PH patients in pregnancy
  3.  “I would tell you that I still think honesty is the best policy. I think you should offer women as much information as we currently know, so they can make informed decisions that are right for them. I think you also do have to really be sensitive to how you’re delivering this information, because remember (for) some women it will have never occurred to them that they can’t have a pregnancy. They may have been planning on having a kids and family and this information can really derail them. So you do have to use sensitivity, but I think you have to do it to accommodate to the patient that you’re seeing. I don’t think there can be a one size fits all approach.”- Dr. Silversides on the challenging topic of how to approach pregnancy termination conversations
  4. “… continue to optimize your care, the better shape the woman is going into delivery. The better outcomes you’ll have at the time of labor and delivery.”- Dr. Silversides

Show notes

1. How do we define pulmonary hypertension (PH) and why is it such a big deal in pregnancy?

  • According to recent guidelines pulmonary hypertension is a mean pulmonary artery pressure ≥ 20 mmHg.
  • The WHO separates PH into 5 groups:
    • Group 1: Pulmonary arterial hypertension (e.g., idiopathic, heritable [BMPR2], anorexigen associated, drug or toxin-associated, HIV, connective tissue disease associated, schistosomiasis, portal hypertension, congenital heart disease, amongst other causes)
    • Group 2: Pulmonary hypertension due to left sided heart disease (e.g., HFrEF, HFpEF, left-side valvular heart disease)
    • Group 3: Pulmonary hypertension due to lung disease or hypoxia: (e.g.,COPD, ILD, OSA, hypoxia without lung disease such as high altitude, developmental lung disorders)
    • Group 4: PH due to pulmonary artery obstructions most commonly Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
    • Group 5: Multifactorial causes such as hematologic disorders (chronic hemolytic anemia, as with myeloproliferative disorders), metabolic disorders (e.g., Gaucher disease, glycogen storage diseases, CKD), and systemic disorders (e.g., pulmonary Langerhans cell histiocytosis, neurofibromatosis, sarcoidosis)
  • The prevalence of pulmonary hypertension and pregnancy is somewhere between 0.011 and 0.02%2. Although rare, this number has been rising due to the number of congenital patients living to childbearing age, as well as the emergence of effective pulmonary vascular therapy.
  • Complications of PH during pregnancy include:
    • The normal physiologic changes of pregnancy (increased plasma volume, increased stroke volume, increased cardiac output, decreased systemic vascular resistance), are poorly tolerated in PH due to an inability to decrease pulmonary vascular resistance and accommodate this increased plasma volume. This can lead to increased right ventricular overload.
    • Decrease in systemic vascular resistance and associated drop in blood pressure can also lead to decreased RV perfusion, contributing to RV failure and making it increasingly difficult to accommodate the extra afterload demand.
    • Pregnancy is both a prothrombotic and a pro-arrhythmic state, and maternal morbidity and mortality may also be related to complications from DVT/PE/arrhythmias, all of which are poorly tolerated by a failing RV with the increased afterload of PH and possible decreased perfusion from lower SVR.
    • Abnormal maternal hemodynamics in PH also contribute to increased fetal and neonatal complications including preterm birth, fetal and neonatal death.

2. How does the severity of PH or the patient’s WHO group impact maternal outcomes?

  • Mortality
    • Overall mortality for PH patients during pregnancy is quite high: Two major systematic reviews covering a time span of 30 years in nearly 200 pregnancies cited total mortality to range between 25-38%. The majority of patients died within the first month after delivery and major causes of death were heart failure, sudden cardiac death and pulmonary embolism4,5  
  • Morbidity
    • A comprehensive study looking at approximately 1500 pregnant women with PH from the national inpatient sample (spanning from 2003-2012) found that the rate of major adverse cardiovascular events was around 24.8%.6
    • Karen et al assessed outcomes in ~150 pregnancies from the ROPAK study according to PH etiology (idiopathic PAH, PH due to congenital heart disease, PH due to left sided disease). Morbidity and mortality were highest in women with idiopathic PAH, and lowest in women with PH due to left sided heart disease. Complications were also higher in patient with severe PH (RVSP >70mmHg).7
    • Meng et al assessed 49 pregnancies from four large centers and found mortality to vary according to PH subgroup:  23% mortality in Group 1 patients, as compared to a 5% mortality in all other WHO groups. Similarly, patients with severe PH (RVSP >50mmHg) had a higher need for advanced therapies as compared to women with mild PH.1
  • Several variables determine risk during pregnancy related to PH, including the WHO group, etiology of PH, functional class, need for PAH medications at baseline, as well as cardiac size and function. 

3. What is the recommended initial workup to help identify and risk stratify patients with PH?

  • Helpful baseline information includes BNP, prior echocardiograms, as well as hemodynamics from prior right heart catheterizations.
  • For those patients previously treated for PH, it is important to identify which medications were used in the past or are currently being prescribed. This particularly important to identify teratogenic medications like endothelin antagonists.
  • One of the most important factors is to identify the patient’s functional status including assessing six-minute walk tests, including O2 saturation, desaturation, and distance walked.
  • Of note, while a RHC helps define the hemodynamic profile, the entire vascular bed is more fragile during pregnancy than in a non-pregnant state, and there have been reports of pulmonary artery rupture with interventions during pregnancy.8 This must be kept in mind when assessing the need for RHC.

4. How do you approach management of patients with PH during pregnancy?

  • Frequent follow-ups and communication with the entire multidisciplinary team are vital. This team should include cardiology, a PH specialist and/or team, high risk obstetrics, and OB anesthesia.
  • Patients should be monitored serially throughout pregnancy with the use of BNP, echocardiography, and assessment of functional status/symptoms.
  • While every patient situation will be different, it is important to provide the patient with as much information as possible to make an informed decision. Given the high-risk nature of pregnancy in these patients, as well as the increased maternal morbidity and mortality, it is important to discuss the option of termination of pregnancy.

5. What is the role of pulmonary vasodilators, and which medications are considered safe in pregnancy?

  • Pulmonary vasodilators should be implemented early to mitigate risk of adverse outcomes as outlined above.
  • Options include: Calcium channel blockers, phosphodiesterase inhibitors (sildenafil, tadalafil), and prostacyclin analogs (epoprostenol, treprostinil).
  • NOTE: endothelin receptor antagonists (such as bosentan, ambrisentan) are teratogenic(Category X) and are contraindicated during pregnancy and in women of childbearing age who are not using reliable contraception. Pregnancy must be excluded before initiation, serially during treatment, and for a period after treatment has been discontinued.
  • CCB/PDE5 inhibitors have been the most commonly reported medications in the series of PH patients during pregnancy. Prostacyclin analogs are considered safe during pregnancy, but their IV formulation may cause challenges in medication administration given the need for continuous administration.

6. How do you approach anticoagulation in PH patients during pregnancy?

  • Pulmonary embolisms are one of the biggest contributors to morbidity and mortality in pulmonary hypertension patients as PE can acutely raise pulmonary artery, and therefore right sided pressures. Currently there are no clear recommendations for full dose anticoagulation in PH patients without risk factors for DVT/PE.
  • Heparin is a large molecule that does not cross the placenta, and therefore considered safe in pregnancy. Typically, LMWH is used as it is considered superior to unfractionated heparin, especially in pregnancy. Other options such as warfarin are considered teratogenic (especially at does >5mg daily), and the class of DOACs have limited data on their safety in pregnancy and should be avoided.
  • Initiation of anticoagulation should be coordinated in conjunction with obstetric hematologists.

7. What are some of the most important delivery considerations to keep in mind for these patients?

  • Delivery timing and location: Consider delivering most patients by 37-weeks gestation (if not earlier) depending on the stability of the patient and fetus. While some women may follow at obstetric hospitals, delivery should take place in a location with backup of a cardiology, ICU, and advanced heart failure teams.
  • Mode of delivery: IF women are stable, vaginal delivery- with an assisted second stage- is preferred as it is associated with fewer complications.
  • Monitoring: In conjunction with OB, consider the use of arterial lines to assess blood pressure, central access for IV medication administration etc. Fetal monitoring is essential.
  • Anesthesia: An epidural with good pain management is preferred, with avoidance of general anesthesia if possible (as GA is associated with greater complications in patients with PH).
  • ECMO: If concerns for patient destabilization arise, VA-ECMO should be immediately available.
  • Post-partum: The majority of complications occur after delivery, with the first post-partum week posing the highest risk period. Close monitoring must be initiated, preferably in a CCU/ICU for several days post-delivery. Early diuresis is paramount, as fluid mobilization after delivery can lead to fluid overload and right heart failure. 

References

1. Meng ML, Landau R, Viktorsdottir O, et al. Pulmonary hypertension in pregnancy a report of 49 cases at four tertiary north American sites. Obstet Gynecol. Published online 2017. doi:10.1097/AOG.0000000000001896

2. Lima F V., Yang J, Xu J, Stergiopoulos K. National Trends and In-Hospital Outcomes in Pregnant Women With Heart Disease in the United States. Am J Cardiol. Published online 2017. doi:10.1016/j.amjcard.2017.02.003

3. Hemnes AR, Kiely DG, Cockrill BA, et al. Statement on pregnancy in pulmonary hypertension from the pulmonary vascular research institute. Pulm Circ. Published online 2015. doi:10.1086/682230

4. Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J. Published online 2009. doi:10.1093/eurheartj/ehn597

5. Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: A systematic overview from 1978 through 1996. J Am Coll Cardiol. Published online 1998. doi:10.1016/S0735-1097(98)00162-4

6. Thomas E, Yang J, Xu J, Lima F V., Stergiopoulos K. Pulmonary hypertension and pregnancy outcomes: Insights from the national inpatient sample. J Am Heart Assoc. Published online 2017. doi:10.1161/JAHA.117.006144

7. Sliwa K, van Hagen IM, Budts W, et al. Pulmonary hypertension and pregnancy outcomes: data from the Registry Of Pregnancy and Cardiac Disease (ROPAC) of the European Society of Cardiology. Eur J Heart Fail. Published online 2016. doi:10.1002/ejhf.594

8. Barash PG, Nardi D, Hammond G, et al. Catheter-induced pulmonary artery perforation. Mechanisms, management, and modifications. J Thorac Cardiovasc Surg. Published online 1981. doi:10.1016/s0022-5223(19)39380-8

9. Marc Humbert, Olivier Sitbon GS. Hypertension, Treatment of Pulmonary Arterial. N Engl J Med. 2004;351:1425-1436.

Two additional excellent sources regarding Pregnancy in PH Patients:

  1. Stout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease. J Am Coll Cardiol. Published online 2019.
  2. Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy. Eur Heart J. Published online 2011. doi:10.1093/eurheartj/ehr218

Guest Profiles

Dr. Candice Silversides
Dr. Candice Silversides

Dr. Candice Silversides is an Associate Professor of Medicine at the University of Toronto.  She serves as the Director of the Pregnancy and Heart Disease program and head of the Obstetric Medicine program. Along with her >180 publications and numerous book chapters, she has contributed to a number of international practice guidelines and consensus statements, and she also helped develop the CARPREG II cardiovascular risk prediction score.

Dr. Kayle Shapero
Dr. Kayle Shapero

Dr. Kayle Shapero is a first year cardiology fellow at the University of Pittsburgh Medical Center. She began her undergraduate training in chemical engineering and completed a PhD in biomedical engineering. She spent her PhD studying tissue engineered heart valves which ultimately piqued her interest in medicine. She went on to complete her medical degree at Tufts Medical School followed by internal medicine residency at Yale. She is currently in her first year of fellowship at UPMC. She is interested cardio-obstetrics and sports cardiology, and is always looking for ways to combine these two clinical and research interests. Outside of the hospital she attempts to keep in shape by training for triathlons and marathons.

CardioNerds Cardioobstetrics Production Team

111. Cardio-Obstetrics: Normal Pregnancy Physiology with Dr. Garima Sharma

CardioNerd Amit Goyal, cardioobstetrics series co-chair Dr. Natalie Stokes, and episode lead Dr. Daniela Crousillat discuss normal cardiovascular physiology in pregnancy with Dr. Garima Sharma, Director of the Cardio-Obstetrics Program and the Ciccarone Center ‘s Associate Director of Preventive Cardiology Education in the Division of Cardiology. They discuss physiology from conception to post-partum, including the key hemodynamic, hormonal, and structural changes associated with normal pregnancy in the absence of pre-existing cardiovascular disease. Series introduction by Dr. Sharonne N. Hayes.

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AbstractPearlsQuotablesNotesReferencesGuest ProfilesProduction Team


Episode Abstract

Join us for a thrilling ride with our expert as we dive into the normal cardiovascular physiology of women through pregnancy. We discuss physiology from conception to post-partum, including the key hemodynamic, hormonal, and structural changes associated with normal pregnancy in the absence of pre-existing cardiovascular disease. We discuss how these physiologic changes manifest the history, physical exam, and key diagnostic testing (ECG, laboratory markers, and echocardiogram). Armed with these basic principles, we join Dr. Garima Sharma on patient consults to learn about potential signs and symptoms of cardiovascular disease in pregnancy and appropriate ways to risk stratify women with pre-existing or acquired cardiovascular disease in pregnancy. Importantly, we delve deeper into the importance of the growing field of cardio-obstetrics in the context of rising maternal mortality and staggering racial disparities in the care and outcomes of women in pregnancy.

Pearls

  • In normal pregnancy, plasma volume increases by up to 50% resulting in an adaptive decrease in systemic vascular resistance (SVR) by 25% and an increase in cardiac output (CO) by ~50% by the 2nd trimester.
  • Brisk carotid upstrokes, an S3 gallop, soft systolic ejection murmurs, pedal edema, and a mildly elevated jugular venous pressure (JVP) can all be normal physiologic findings in pregnancy in the context of no other signs/symptoms to suggest heart failure.
  • A normal NT-proBNP among pregnant patients with pre-existing cardiovascular disease has a high negative predictive value for predicting adverse maternal cardiac outcomes.
  • Pregnancy risk predictor tools (mWHO, CARPREG II, ZAHARA) are a crucial component of pre-conception counseling to help predict which women with existing cardiovascular disease are at highest risk for adverse maternal outcomes.
  • The U.S. ranks 1st in the world for maternal mortality among developed nations and cardiovascular disease is the leading cause of pregnancy-associated mortality in the U.S. Non-Hispanic Black are 3.5 times more likely to die from pregnancy as compared to White women.

Quotables

  • “You don’t know where you are going until you know where you have been” – Dr. Garima Sharma on the importance of holding on to hope when encountering difficult situations in our training and career pathways.
  • “Do not fear the pregnant patient! The pregnant patient is going through a normal physiologic process in her life, and the more we are familiar with it, the less we fear it” – Dr. Garima Sharma on taking care of pregnant patients.
  • “If you are going to move the needle on maternal mortality and in making a long-term sustainable change in the lives of these women, you have to focus on prevention” – Dr. Garima Sharma on the importance of prevention in reducing maternal mortality.
  • “Be empathetic. For most women, pregnancy is a normal state.  These women need your help!” – Dr. Garima Sharma on the importance of taking care of women in pregnancy.

Show notes

  1. What are the normal hemodynamic changes that occur in pregnancy? Let’s talk physiology!
  • Pregnancy, nature’s most grueling stress test, is a dynamic process associated with significant hemodynamic and physiological adaptations in the cardiovascular system which have evolved to support the needs of a developing fetus.
  • Predictable and expected hemodynamic changes occur during pregnancy for all women. Healthy women can adapt without significant consequences, whereas in women with underlying cardiac conditions, these changes may unmask a previously unknown condition or exacerbate existing abnormal hemodynamics.

Adaptive Physiologic Changes of the Cardiovascular System (1)

Source:  Me Mehta LS, Warnes CA, Bradley E et al. Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association. Circulation 2020;141:e884-e903. Supplemental Table 1: Physiologic Changes Throughout Normal Pregnancy Compared to Pre Pregnancy State (2)
  • Plasma volume
    • Increases by about 50-75% by the 2nd trimester of pregnancy to meet greater circulatory needs of placenta and maternal organs
    • Erythropoietin causes an increase in red cell mass by 20-30% leading to relative dilution and “physiologic” anemia of pregnancy
  • Systemic vascular resistance (SVR)
    • To accommodate the increase in plasma volume, vasodilatation and vascular remodeling occur with a reduction in SVR
    • SVR decreases starting early in the 1st trimester and falls by 25-30% in the 2nd trimester potentiated by progesterone and estrogen-induced vasodilatation
    • Decreased SVR results in activation of the renal angiotensin-aldosterone system (RAAS) to maintain blood pressure and salt/water balance
  • Cardiac output (CO)
    • Increases by ~ 50% during pregnancy (up to 75% for a twin gestation!), starting at 5 weeks of gestation, and peaks at about 18-24 weeks in the 2nd trimester
    • CO (stroke volume (SV) x heart rate (HR)) increases predominantly via an increase in SV, but also an increase in HR by about 10-15 bpm by the 3rd trimester due to activation of the sympathetic system

There are a multitude of other physiological changes that allow our cardiovascular systems to adapt to the normal hemodynamics of pregnancy.

  • Respiratory:  Increase in metabolic rate & O2 consumption, minute ventilation and tidal volume resulting in a mild compensatory respiratory alkalosis.
  • Renal: Systemic vasodilation results in 50% increase in renal plasma flow and glomerular filtration rate (GFR), activation of RAAS to maintain fluid and electrolyte balance.
  • Hematologic: “Physiologic” anemia of pregnancy due to increase in plasma volume > red blood cell mass, increased production of coagulation factors with promotion of a pro-thrombotic state.
  • Endocrine: Increase in total cholesterol, triglycerides, LDL (by 50%) and decrease in HDL; mild insulin resistance.

Labor & Delivery and Post-Partum Period:

Labor: 

  • The maximum CO associated with pregnancy occurs during labor and immediately post-partum.
  • Repeated Valsalva maneuvers with a doubling of CO (up to 10L!) in active labor
  • Each uterine contraction displaces about 300-500 mL of blood back into the maternal systemic circulation

Post-partum:

  • Immediate: Caval decompression from evacuation of gravid uterus leads to marked increase in venous return (“auto transfusion”) back into the maternal systemic circulation
  • Two weeks post-partum: Maternal hemodynamics largely return to the pre-pregnancy state!

2. How are the normal physiological changes of pregnancy reflected in the physical exam and diagnostic cardiac testing? When should we worry?

  • Physical Exam (2)
    • Heart rate: Increases by 10-15 bpm by 3rd trimester, mild sinus tachycardia
    • Blood pressure: Decrease of 10-15 mm Hg in both SBP and DBP, nadiring in 2nd trimester, improving to pre-pregnancy state in 3rd trimester
    • Weight: 25-35 lbs considered normal total gestational weight gain in patients who are normal weight pre-partum
    • Cardiac exam: Mildly elevated jugular venous pressure with more prominent x and y descents, brisk carotid upstrokes, soft, systolic ejection murmur (flow murmur), S3 gallop, mild pedal edema, varicose veins, mammary flow murmur
  • ECG:
    • Mild sinus tachycardia
    • Infrequent premature atrial and ventricular atrial contractions
    • Leftward axis deviation
    • Q waves in inferior (II, III, aVF) and/or lateral (V4-V6) leads due to heart’s spatial shift left, anterior, and in the transverse plane to accommodate the gravid uterus
  • Cardiac Biomarkers
    • NT-proBNP
      • Increase up to two-fold in pregnancy but should remain within normal range
      • Important clinical utility in patients with pre-existing cardiac disease to serially assess changes throughout pregnancy
        • BNP <100 pg/nL among women with cardiovascular disease has a 100% negative predictive value for identifying cardiac events during pregnancy (3)
        • NT pro BNP <128 at 20 weeks has 97% NPV for maternal complications (4)
  • Echocardiography: (5)
    • Increase in LV volumes (but remaining within normal limits) and 50% increase in LV and RV mass as response to increased blood volume and CO
    • “Physiologic” left ventricular hypertrophy
    • Left ventricular ejection fraction remains unchanged
    • Mild increase in aortic root diameter
    • Trivial MR, TR, and PR (not typically AR!)
    • Trace, physiologic pericardial effusion (can be normal in up to 40%)

When should we worry?

  • Diastolic murmurs
  • Signs of congestive heart failure (crackles, elevated JVP/Kussmaul’s sign, marked lower extremity edema or weight gain)
  • Loud P2 or RV heave which could signal elevated pulmonary pressures/pulmonary HTN
  • Elevated NT-proBNP
  • Large pericardial effusion or symptoms of pericarditis

3. What are the available pregnancy risk predictor scores for the risk stratification of women with pre-existing cardiovascular disease who are interested in achieving pregnancy?

Modified World Health Organization (mWHO) Classification (6)

  • Most commonly used risk prediction tool to estimate individual maternal cardiovascular risk in women with pre-existing CVD based on known cardiac pathology
  • Classification ranges from simple lesions in Class I (mitral valve prolapse, repaired ASDs) to Class IV (pulmonary arterial hypertension, severe MS/AS, peripartum cardiomyopathy) in which pregnancy is typically advised against due to high (20-25%) maternal risk of adverse events

CARPREG (CArdiac Disease in PREGnancy Study) II Risk Score (7)

  • Developed from the prospective Canadian Cardiac Disease in Pregnancy Study in women with pre-existing cardiac disease, the score includes 10 predictors of a cardiac event,  including a prior history of cardiac events, baseline NYHA functional class, and late access to prenatal care to better determine overall risk (different than the mWHO classification which is based on just the cardiac lesion)
  • Weight-based point system: 5% risk of complications in lowest risk group (0 to 1 points) versus >40% risk with > 4 points
Source: Silversides CK, Grewal J, Mason J et al. Pregnancy Outcomes in Women With Heart Disease: The CARPREG II Study. J Am Coll Cardiol 2018;71:2419-2430. (7)

ZAHARA Risk Score

  • Weighted scoring system based on retrospective cohort of patients with pre-existing congenital heart disease only
  • Least commonly used risk tool as based on limited patient population (ACHD)

4. What are the most common cardiac complications which can occur in women with pre-existing cardiovascular disease in pregnancy and when do they occur?

  • Arrythmias: Atrial fibrillation is the most common arrythmia in women with underlying structural heart disease. PACs/PVCs can be common in normal pregnancy. If they occur, arrythmias are most common in the 2nd trimester.
  • Heart failure: Worsening/decompensation of left ventricular function, particularly in women with personal or family history of cardiomyopathy and history of peripartum cardiomyopathy. The development of heart failure and pulmonary edema are most common in the 3rd trimester or immediately (<1 week) post-partum. (7)
  • Don’t forget about other adverse pregnancy outcomes (APOs) which are associated with long term cardiovascular complications! (8)
    • Maternal Complications: Hypertensive disorders of pregnancy (i.e. pre-eclampsia), gestational diabetes
    • Obstetrical/Fetal Complications: Preterm birth, small for gestational age infant

5. What is the state of maternal mortality in the U.S. compared to the rest of the world, and what is this rise in maternal mortality attributed to?

  • The United States ranks 1st among developed nations in maternal mortality (9)
  • Cardiovascular disease is the leading cause of pregnancy-associated mortality in the United States and has gradually increased over time (7 to 17 deaths per 100,000 live births from 1989-2017)
  • Maternal mortality is attributed to 1) rising maternal age, 2) comorbid pre-existing conditions (HTN, diabetes, obesity), and 3) the growing number of women with congenital heart disease achieving childbearing age
    • Increase in obesity (41% of U.S. population) and chronic hypertension are two of the most important preventable risk factors!
    • Pre-pregnancy HTN has doubled among women in past decade and disproportionately affects rural communities and racial groups (10)
  • Over 700 women a year die of complications related to pregnancy each year in the United States, and it is thought that about two-thirds of those deaths are preventable.
  • Non-Hispanic Blacks and American Indian/Alaskan Native women are 3-4x more likely to die from a pregnancy-related cause compared to White women (11).
Source: Petersen EE, Davis NL, Goodman D, et al. Racial/ethnic disparities in pregnancy-related deaths — United States, 2007–2016. MMWR Morb Mortal Wkly Rep. 2019;68:762–765. (11

References

  1. Sanghavi M, Rutherford JD. Cardiovascular physiology of pregnancy. Circulation 2014;130:1003-8.
  2. Mehta LS, Warnes CA, Bradley E et al. Cardiovascular Considerations in Caring for Pregnant Patients: A Scientific Statement From the American Heart Association. Circulation 2020;141:e884-e903.
  3. Tanous D, Siu SC, Mason J et al. B-type natriuretic peptide in pregnant women with heart disease. J Am Coll Cardiol 2010;56:1247-53.
  4. Kampman MA, Balci A, van Veldhuisen DJ et al. N-terminal pro-B-type natriuretic peptide predicts cardiovascular complications in pregnant women with congenital heart disease. Eur Heart J 2014;35:708-15.
  5. Liu S, Elkayam U, Naqvi TZ. Echocardiography in Pregnancy: Part 1. Current cardiology reports 2016;18:92.
  6. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Kardiologia polska 2019;77:245-326.
  7. Silversides CK, Grewal J, Mason J et al. Pregnancy Outcomes in Women With Heart Disease: The CARPREG II Study. J Am Coll Cardiol 2018;71:2419-2430.
  8. Søndergaard MM, Hlatky MA, Stefanick ML et al. Association of Adverse Pregnancy Outcomes With Risk of Atherosclerotic Cardiovascular Disease in Postmenopausal Women. JAMA cardiology 2020;5:1390-8.
  9. Pregnancy Mortality Surveillance System.       https://www.cdc.gov/reproductivehealth/maternalinfanthealth/pregnancy-mortality-surveillancesystem.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Freproductivehealth%2Fmaternalinfanthealth%2Fpmss.html. Accessed January 18th, 2021.
  10. Cameron NA, Molsberry R, Pierce JB et al. Pre-Pregnancy Hypertension Among Women in Rural and Urban Areas of the United States. J Am Coll Cardiol 2020;76:2611-2619.
  11. Petersen EE, Davis NL, Goodman D et al. Racial/Ethnic Disparities in Pregnancy-Related Deaths – United States, 2007-2016. MMWR Morbidity and mortality weekly report 2019;68:762-765.

Guest Profiles

Garima Sharma M.B.B.S.
Garima Sharma M.B.B.S.

Dr. Garima Sharma is an Assistant Professor of Medicine in the Division of Cardiology and Department of Medicine at Johns Hopkins University. She serves as Director of the Cardio-Obstetrics Program and the Ciccarone Center ‘s Associate Director of Preventive Cardiology Education in the Division of Cardiology. Her clinical and research interests are in CVD in pregnancy specifically adverse pregnancy outcomes and CV risks, hypertensive disorders of pregnancy, and gender equity.

Daniella Crousillat, MD
Daniella Crousillat, MD

Dr. Daniella Crousillat is an advanced echocardiography fellow at Massachusetts General Hospital in Boston, MA. She is interested in sex differences in valvular heart disease and pregnancy-associated CVD with a special focus on health disparities and the care of vulnerable patient populations.

CardioNerds Cardioobstetrics Production Team

103. Case Report: A Rare Cause of Postpartum Angina and Arrest – University of Maryland

CardioNerds (Amit Goyal & Daniel Ambinder) join University of Maryland cardiology fellows (Manu Mysore, Adam Zviman, and Scott Butler) for some cardiology and an Orioles game in Baltimore! They discuss a rare cause of postpartum angina and cardiac arrest due to coronary vasculitis. Program director Dr. Mukta Srivastava provides the E-CPR expert segment and a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Rick Ferraro with mentorship from University of Maryland cardiology fellow Karan Desai.

This case has been published in JACC Case Reports!

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Ep 103 Coronary Vasculitis University of Maryland
Episode graphic by Dr. Carine Hamo



Patient Summary

A woman in her early 30s with a past medical history of Hashimoto’s thyroiditis and one prior miscarriage at <8 weeks presented with chest pain about 6 weeks postpartum from the birth of her third child. In the ED, she continued to report intermittent sharp chest discomfort and found to have a diastolic decrescendo murmur at the left upper sternal border and labs demonstrating a troponin-I of 0.07 ng/dL. Join the UMD Cardionerds for the incredible course and story of this young patient as we go through the differentia and approach to postpartum chest pain and ultimately arrive in a very rare diagnosis!   For a detailed course, enjoy the JACC case report.


Case Media

Visit the JACC Case Reports to review the case media!


Episode Schematics & Teaching


The CardioNerds 5! – 5 major takeaways from the #CNCR case

1. How Do We Evaluate Chest Pain in Younger Patients 

  • Start with the same things as everyone else!  Think broadly about the big three concerning etiologies of chest pain: Cardiac, Gastric, and Pulmonary (The excellent Clinical Problems Solvers 4+2+2 construct here is always a great resource. Find them at: https://clinicalproblemsolving.com/dx-schema-chest-pain/).   
  • Of course it is important to think about non-life threatening etiologies as well – esophageal spasm, gastric ulcer, rib fracture, skin lesion, among many others – given that high-risk chest pain is less likely in younger adults.  
  • While less common, acute coronary syndrome is not uncommon in young patients, as 23% of patients with MI present at age <55 years.  

2. What About Chest Pain in Women?  

  • As has been discussed on the Cardionerds podcast (Listen to episodes with Dr. Nanette Wenger, Dr Martha Gulati, and Dr. Leslie Cho), women generally present with acute coronary syndrome at a later age, with a higher burden of risk factors than men, and with greater symptom burden but are less likely to be treated with guideline-directed medical therapies, undergo cardiac catheterization and receive timely reperfusion. In one study of young patients with acute MI, women – 19% of cases overall – were less likely to undergo revascularization or receive guideline-directed therapy 
  • The construct of classifying chest pain as “typical” and “atypical” likely leads to misdiagnosis or delayed diagnosis of acute myocardial infarction in women. Rather, it is important to recognize that while symptoms may not be “typical” for angina, coronary disease can manifest in many different ways.  
  • While many women will presents with chest pain suggestive of angina, women are more likely than men to present with dyspnea, indigestion, weakness, nausea/vomiting and/or fatigue. Note, shoulder pain and arm pain are twice as predictive of an acute myocardial infarction diagnosis in women compared with men.  
  • Furthermore, while obstructive epicardial disease remains the primary cause of acute MI in young women, it is also important to keep other causes of chest pain such as MINOCA, SCAD (see the UCLA episode), peripartum cardiomyopathy (see the Penn and MCW episodes), or coronary vasculitis on the differential. While these etiologies are rare, they are disproportionately represented in young women.  

3. How do we think about categorizing vasculitis? 

  • Vasculitis is a broad term encompassing many forms of vessel wall (including arteries, veins or capillaries) inflammation.  This can be secondary to autoimmunity, infection, drug reaction, and malignancy to name a few underlying causes.  
  • Generally vasculitis is divided by large vessel (e.g., Takayasu, Giant Cell), medium vessel (e.g., Polyarteritis Nodosa), and small vessel etiologies (e.g., Granulomatosis with Polyangitis, Eosinophilic Granulomatosis with Polyangiitis, Microscopic Polyangitis, Immune-mediated Vasculitis, amongst others). This characterization follows the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitis.  
  • Other important categories includes variable vessel vasculitis (e.g., Behcet’s Disease, Cogan’s Syndrome) and vasculitis associated with systemic disease (e.g., Lupus vasculitis, Rheumatoid vasculitis, Sarcoid vasculitis).  

4. What Does Vasculitis Look Like in the Heart? 

  • While inflammation can occur throughout the heart – e.g., pericarditis or myocarditis – vasculitis in the heart refers specifically to inflammation of the coronary arteries. This is a relatively rare process, with <10% of vasculitis patients exhibiting cardiac involvement.  
  • Patients with coronary vasculitis rarely present with isolated coronary involvement and typically have systemic manifestations, such as constitutional symptoms in addition to cardiac symptoms (e.g., angina, heart failure, arrhythmia). Examination may reveal asymmetric pulses or BP readings between limbs and arterial bruits, with imaging revealing multi-organ infarcts without a clear embolic origin. Amongst the vasculitides, Takayasu Arteritis (TA) is one of the more frequent etiologies of coronary arteritis.  
  • In Takayasu Arteritis (TA), the affected arteries are typically the aorta and its major branches. In contrast to giant cell arteritis (GCA), TA is quite rare and tends to have onset <40 years age; however, for both diagnoses coronary involvement is rare. TA patients will typically have constitutional symptoms and may have diminished/absent arterial pulses often accompanied by bruits. Weakness of the arterial walls may lead to aneurysms and specifically aortic root aneurysm may result in aortic valve insufficiency. When involving the coronaries, there are three main type of TA lesions: stenosis or occlusion of the ostia/proximal segments (Type 1); diffuse or focal coronary vasculitis involving all the epicardial branches or focal areas (Type 2); coronary aneurysms (Type 3). 

5. What Are the Complications of Coronary Vasculitis?  

  • The consequences of coronary vasculitis are variable and much of the data we have comes from case reports. As in the case presented, severe coronary ischemia and its complications, including arrhythmia and cardiac arrest, are a major concern. However, cardiac arrest is rarely the first presentation of coronary vasculitis, especially if it is detected early. The manifestations of coronary vasculitis are also going to be dependent on the specific etiology of the arteritis.  
  • Amongst the medium vessel vasculitis and specifically polyarteritis nodosa, 15-20% of patients will have cardiac involvement, with major complications including heart failure, myocardial infarction, or arrhythmia.  
  • Amongst the small vessel vasculitis, eosinophilic granulomatosis with polyangiitis is the most common culprit for cardiac involvement, primarily secondary to eosinophilic toxicity. Cardiac involvement is a major cause of mortality and poor prognostic sign in EGPA. 

The CardioNerds Cardiology Case Reports series shines light on the hidden curriculum of medical storytelling. We learn together while discussing fascinating cases in this fun, engaging, and educational format. Each episode ends with an “Expert CardioNerd Perspectives & Review” (E-CPR) for a nuanced teaching from a content expert. We truly believe that hearing about a patient is the singular theme that unifies everyone at every level, from the student to the professor emeritus.

We are teaming up with the ACC FIT Section to use the #CNCR episodes to showcase CV education across the country in the era of virtual recruitment. As part of the recruitment series, each episode features fellows from a given program discussing and teaching about an interesting case as well as sharing what makes their hearts flutter about their fellowship training. The case discussion is followed by both an E-CPR segment and a message from the program director.

Cardionerds Cardiology Podcast Presents CardioNerds Case Report Series

References

  1. Kostner, M. J., & Warrington, K. J. (2019, March 13). Vasculitis of the Coronary Arteries. ACC.org. 
  2. Ward, E. V., Nazari, J., & Edelman, R. R. (2012). Coronary artery vasculitis as a presentation of cardiac sarcoidosis. Circulation125(6), e344-e346. 
  3. Awad, H. H., McManus, D. D., Anderson Jr, F. A., Gore, J. M., & Goldberg, R. J. (2013). Young patients hospitalized with an acute coronary syndrome. Coronary Artery Disease24(1), 54-60. 
  4. Bugiardini, R., Cenko, E. (2020). Sex differences in myocardial infarction deaths. Lancet, 396:72–73 
  5. DeFilippis, E.M., Collins, B.L., Singh A., et. al Women who experience a myocardial infarction at a young age have worse outcomes compared with men: the Mass General Brigham YOUNG-MI registry, European Heart Journal, ehaa662 
  6. Miloslavsky, E., & Unizony, S. (2014). The heart in vasculitis. Rheumatic Disease Clinics40(1), 11-26. 
  7. Mehta LS, Beckie TM, DeVon HA et al; American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology, Council on Epidemiology and Prevention, Council on Cardiovascular and Stroke Nursing, and Council on Quality of Care and Outcomes Research. (2016) Acute Myocardial Infarction in Women: A Scientific Statement From the American Heart Association. Circulation. Mar 1;133(9):916-47. doi: 10.1161/CIR.0000000000000351.  

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