CardioNerds (Amit Goyal & Daniel Ambinder) join University of Pittsburgh Medical Center cardiology fellows (Agnes Koczo, Natalie Stokes, and Kayle Shapero) for a boat cruise down the Allegheny river as we tour all over beautiful Pittsburgh! They discuss an important case of severe pre-eclampsia, and explore some of the exciting dimensions of cardio-obstetrics. Dr. Malamo Eleni Countouris provides the E-CPR and program director Dr. Katie Berlacher provides a message for applicants. Episode notes were developed by Johns Hopkins internal medicine resident Tommy Das with mentorship from University of Maryland cardiology fellow Karan Desai.  

Jump to: Patient summary – Case media – Case teaching – References

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.

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A G12P7 woman in her mid 30s in the third trimester of pregnancy presented with two months of progressive shortness of breath, orthopnea, and abdominal distension. She has a history of chronic HTN, untreated OSA, and obesity. Evaluation revealed a BP of 147/76 and spot urine protein:creatinine ratio elevated to 0.6, which in the context of her presentation was concerning for preeclampsia superimposed on chronic hypertension. TTE showed preserved ejection fraction, flattened interventricular septum during systole consistent with RV pressure overload, and moderate pulmonary HTN. 

She was diuresed with IV furosemide with improvement in symptoms and kept on ASA 81mg. The etiology of her elevated PA pressures was thought to be multifactorial, including untreated OSA for which she was started on CPAP. She was ultimately discharged on oral diuretics, and underwent an uncomplicated spontaneous vaginal delivery at 37 weeks. After delivery, follow-up in a clinic specializing in improving cardiovascular health in women with history of hypertensive disorders of pregnancy was arranged.  

• A
• B
• C

A. ECG: Sinus tachycardia otherwise unremarkable
B. CXR: Within limitations of respiratory motion, no focal airspace consolidation; no pleural effusions
C. TTE: EF 55-60%, flattened IVS c/w RV pressure overload; normal RV size and function; mod TR; moderate pulmonary HTN (PASP 52mmHG); normal diastolic function

1. Cardionerds, we all should be familiar with #CardioObstetrics. What are the hypertensive disorders of pregnancy? 

• There are four major categories for hypertensive disorders in pregnancy: (1) chronic hypertension (2) gestational hypertension; (3) preeclampsia (along with eclampsia and HELLP syndrome); (4) chronic hypertension with superimposed preeclampsia.  
  • Chronic Hypertension: Note, the definition of chronic hypertension was updated in the 2017 ACC/AHA guidelines as SBP ≥ 130 or DBP ≥ 90, but the diagnostic criteria for gestational hypertension, pre-eclampsia and chronic hypertension with super-imposed pre-eclampsia have not changed at this time.  
  • Gestational Hypertension (per ACOG guidelines): defined as SBP ≥  140 mmHg or DBP ≥  90 mmHg at least 4 hours apart diagnosed after 20 weeks of gestation without proteinuria or severe features of pre-eclampsia (e.g., renal insufficiency, elevated liver enzymes, thrombocytopenia, hemolysis, pulmonary edema, or CNS symptoms) 
  • Preeclampsia: diagnosis requires  (1) SBP ≥ 140 mmHg or DBP ≥  90 mmHg at least 4 hours apart after 20 weeks gestation or SBP ≥ 160 mmHg or DBP ≥ 110 mmHg once and (2) end organ damage. This includes proteinuria (≥ 300 mg/24hr urine collection, protein/creatinine ratio of ≥ 3 mg/dL, or dipstick reading of 2+ protein if other methods are not available), thrombocytopenia (<100k), renal insufficiency (doubling of serum Cr in the absence of other renal disease or serum Cr > 1.1 mg/dL), elevated liver enzymes (at least 2x upper limit of normal), pulmonary edema, or neurological symptoms (e.g., new onset headache not responding to medications or visual disturbances not attributable to another diagnosis).  
    • Eclampsia: diagnosed when new-onset, grand mal seizure occurs in patients with pre-eclampsia. 
    • HELLP Syndrome: diagnosed when Hemolysis, Elevated Liver enzymes, and Low Platelets are the predominant features. HELLP is likely a subset of preeclampsia. Note, not all patients will have hypertension.  
  • Chronic hypertension with superimposed preeclampsia: (1) characterized by sudden increase in blood pressure that was previously controlled or recent up-titration of antihypertensives to manage blood pressure and/or (2) new onset proteinuria or increase in pre-existing proteinuria 

2. This case featured a patient with super-imposed pre-eclampsia; what is pathophysiology behind this disorder? 

• The pathophysiology of preeclampsia is complex and includes multi-organ manifestations. The initial insult is thought to be secondary to abnormal trophoblast (the outer cell layer of the blastocyst which eventually gives rise to the embryo) invasion of the endometrium. Normally, as trophoblasts implant in the endometrium, the small myometrial spiral arteries remodel with loss of smooth muscle and elastic lamina from the vessel wall. This allows increased blood flow to the placenta.  
• In preeclampsia, there is incomplete spiral artery remodeling which can lead to placental ischemia. The incomplete arterial transformation is thought to be mediated by a number of factors, including soluble fms-like tyrosine kinase-1 (sFlt-1). sFlt-1, which circulates in the maternal bloodstream, has been implicated as an underlying culprit to the multi-system endothelial dysfunction we see in pre-eclampsia (e.g., CNS, renal dysfunction). There are other factors involved as well that ultimately lead to widespread oxidative stress, abnormal vascular reactivity, microemboli, and the clinical features of preeclampsia.  
• There are additionally immunologic and genetic factors that lead to a preeclampsia phenotype by leading to a pro-inflammatory state and reduced trophoblast invasion.  

3. Clearly, pre-eclampsia can have severe adverse effects on mother and child. Which patients are at increased risk of pre-eclampsia, and what can be done to lower their risk? 

• High risk factors for developing preeclampsia include: diabetes, chronic hypertension, chronic kidney disease, multifetal gestation, autoimmune disorders (particularly systemic lupus erythematosus and antiphospholipid syndrome), and previous pregnancy with preeclampsia. Other risk factor include obesity, maternal age over 35 years, and nulliparity. 
• There is no consensus guideline on what defines moderate to high risk. Following the USPSTF recommendations, any pregnant woman with a high risk factor or several moderate risk factors should be advised to start low-dose aspirin after 12 weeks of gestation to reduce the risk of preeclampsia. A recent Cochrane review that included trial data from nearly 37,000 women found aspirin prophylaxis reduced risk of preeclampsia by 18%.  
• Calcium supplementation may be of benefit to prevent preeclampsia in women with low-baseline calcium intake. The proposed mechanism is that hypocalcemia may stimulate PTH or renin release, increasing intracellular calcium including in vascular smooth muscle. This may result in vasoconstriction and higher blood pressure and calcium supplementation may attenuate this process.  
• There is an ongoing clinical trial to investigate the role of Pravastatin in the prevention of preeclampsia.  

4. What if my patient has chronic HTN or gestational HTN? How do I approach the hypertensive pregnant patient? 

• An ounce of prevention is worth a pound of cure! In hypertensive women who may become pregnant, nifedipine, labetalol, hydralazine, or methyldopa are preferred over teratogens like ACE inhibitors, ARBs, or direct renin inhibitors.  
• Severe HTN (SBP ≥160, DBP ≥110) should always be treated to avoid pulmonary edema, stroke or placental abruption. A more conservative approach can be taken in mild to moderate HTN, as aggressive blood pressure lowering can compromise fetal circulation. However, the optimal blood pressure to initiate treatment below this threshold is less well defined and should be individualized to the patient including factors like underlying cardiovascular disease and baseline blood pressure.  
• The timing of delivery is a critical aspect of managing a patient’s hypertension. For a detailed discussion, review the ACOG practice bulletin.  

5. How does a hypertensive disorder of pregnancy change a patient’s cardiovascular risk? 

• A history of a hypertensive disorder of pregnancy is an important risk factor for future cardiovascular disease. These patients are more likely to experience hypertension, ischemic heart disease, heart failure, chronic kidney disease, diabetes, and stroke.  
• Remember that between 5-10% of pregnancies are complicated by a hypertensive disorder. Given the prevalence and prognostic importance of these disorders, it is crucial to take a detailed obstetrics history when caring for women with cardiovascular disease! 
• Enjoy prior episodes discussing cardiovascular risk in women: 
  • Ep #18 – Women’s CV Health with Dr. Martha Gulati 
  • Ep #41 – Women’s CV Prevention with Dr. Leslie Cho 
  • Ep #52 – Women’s Heart Health & Women in Cardiology with Dr. Nanette Wenger 

References

• Thilaganathan, B., & Kalafat, E. (2019). Cardiovascular System in Preeclampsia and Beyond. Hypertension (Dallas, Tex. : 1979), 73(3), 522–531. 
• ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy. (2018). Obstetrics and gynecology, 132(1), e44–e52.  
• Wenger, N. K., Arnold, A., Bairey Merz, C. N. et al. (2018). Hypertension Across a Woman’s Life Cycle. Journal of the American College of Cardiology, 71(16), 1797–1813.  
• Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/ 
• Brown, M. A., Magee, L. A., Kenny, L. C. et al. (2018). Hypertensive Disorders of Pregnancy: ISSHP Classification, Diagnosis, and Management Recommendations for International Practice. Hypertension (Dallas, Tex. : 1979), 72(1), 24–43.  
• Sanghavi, M., & Rutherford, J. D. (2014). Cardiovascular physiology of pregnancy. Circulation, 130(12), 1003–1008.  
• Seely, E. W., & Ecker, J. (2011). Clinical practice. Chronic hypertension in pregnancy. The New England journal of medicine, 365(5), 439–446.  
• Honigberg, M. C., Zekavat, S. M., Aragam, K. et al. (2019). Long-Term Cardiovascular Risk in Women With Hypertension During Pregnancy. Journal of the American College of Cardiology, 74(22), 2743–2754.  
• Ives, C. W., Sinkey, R., Rajapreyar, I., et al. (2020). Preeclampsia-Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 76(14), 1690–1702.  
• Duley, L., Meher, S., Hunter, K. E., et al. (2019). Antiplatelet agents for preventing pre-eclampsia and its complications. The Cochrane database of systematic reviews, 2019(10), CD004659.  
• Ying, W., Catov, J. M., & Ouyang, P. (2018). Hypertensive Disorders of Pregnancy and Future Maternal Cardiovascular Risk. Journal of the American Heart Association, 7(17), e009382.  

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• Amit Goyal, MD
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