CardioNerds (Amit Goyal and Daniel Ambinder), cardioobstetrics series co-chair Dr. Natalie Stokes, Northwestern University CardioNerds Ambassador Dr. Loie Farina, and episode lead fellow, Dr. Agnes Koczo (University of Pittsburgh) join Dr. Julie Damp of Vanderbilt University Associate Director of the VUMC Cardiovascular Disease Fellowship for a discussion about pregnancy, heart failure, and peripartum cardiomyopathy. Episode introduction by Dr. Luis Calderon. Audio editing by Pace Wetstein.
In this episode we discuss the presentation of peripartum cardiomyopathy (PPCM), tips for examining a late antepartum patient, and review management of pregnancy complicated by cardiogenic shock. Weaved throughout the case, we discuss important concepts including the role of prolactin in PPCM which factors into both treatment decisions like prescribing bromocriptine (what!) as well as counseling on breastfeeding. Be sure to tune in to hear Dr. Damp’s review of the latest evidence regarding the diagnosis and management of PPCM, as well as her personal experience counseling patients on heart failure therapies and ICD placement in the context of important factors like breastfeeding status, contraception and future pregnancies.
1) PPCM most typically presents in the early postpartum period and is defined as an LVEF <45% (with or without LV dilatation and RV involvement) and no other explanation for the cardiomyopathy.
2) Patients with PPCM can present with classic heart failure symptoms, which may be challenging to distinguish from the typical symptoms and signs of pregnancy. To help differentiate pathology from normal physiology, consider the constellation of exam findings (e.g., isolated peripheral edema versus peripheral edema, +S3, elevated JVD and rales), the severity of the findings, and comparison of symptoms/findings to prior pregnancies.. There are no specific serum markers for PPCM yet.
3) Prolactin and a vascular etiology have been implicated in the pathogenesis of PPCM. There are ongoing trials to evaluate treatment with bromocriptine, which blocks prolactin (look out for upcoming the REBIRTH RCT examining this!). Importantly, there is no clear evidence that breastfeeding is prohibitive to myocardial recovery and should not be discouraged given benefits to both mom and baby.
4) Many of these patients recover, but those at highest risk are those with severely depressed LV systolic function, dilated LVs, RV involvement, and of African descent.
5) Goal directed medical therapy with beta-blockers in both ante- and postpartum period is a cornerstone of therapy. ACEi/ARB/MRA/ARNI are contraindicated in pregnancy but may be added postpartum and with breastfeeding.
1. “It can be so challenging to distinguish symptoms (in a pregnant patient) from cardiac disease! One thing to keep in mind is severity – the more pronounced a finding or symptoms, the more concerning.” – Dr. Julie Damp
2. ”We often have more options than we think in medical management for heart failure through pregnancy and breastfeeding, but they do need some adjustments from our usual therapies.” -Dr. Julie Damp
3. “Start discussions about prognosis, monitoring, future pregnancies, and contraception early!” -Dr. Julie Damp
1. How do you distinguish findings of normal pregnancy from signs and symptoms of heart failure?
- Pregnant patients may normally have basal rales that typically clear with coughing, laterally shifted PMI, bounding PMI and pulse, JVD, S3, systolic murmur, edema/tense soft tissue, and heart rate elevation.
- Patients may feel short of breath, exertional fatigue, orthopnea, and palpitations. Think about the combination and severity of signs/symptoms to distinguish normal from abnormal (CHF) in your exam. For instance, isolated mild lower extremity edema in a patient who is otherwise relatively asymptomatic with no other concerning findings on exam will be approached differently than a patient with LE edema along with rales, S3 and significant dyspnea.
- Asking patients who have had a prior pregnancy to compare their symptoms with the prior pregnancy can be helpful as well.
- Timing of symptoms is also an important thing to consider. For patients with underlying cardiac disease, they may start to develop symptoms earlier in pregnancy as hemodynamic changes evolve.
2. Given the prolactin hypothesis, should I use bromocriptine for treatment of PPCM and counsel my patients against breastfeeding?
- Various etiologies regarding the pathogenesis of PPCM have been proposed including myocarditis-like process, autoimmune causes, dietary deficiencies of selenium, as well as remodeling from a maladaptive response to hemodynamic changes in pregnancy.
- More recently, a vascular-hormonal hypothesis has been proposed where potent anti-angiogenic hormones are released creating a vasculotoxic environment. Specifically, a 16-kda fragment of prolactin, named vasohibin, has been implicated in the pathogenesis.
- This has led to several RCTs in Germany and Burkina Faso evaluating bromocriptine (a dopamine receptor agonist which inhibits prolactin secretion) for the treatment of PPCM. As more data emerges, the role of bromocriptine will be better defined. For now, patients with more severe PPCM or risk factors that suggest a worse prognosis may benefit from its use. This certainly must be a shared decision as there are risks to bromocriptine including inhibiting lactation and thromboembolism.
- Use of bromocriptine should be paired with anticoagulation.
- In the Investigations in Pregnancy Associated Cardiomyopathy (IPAC) study, 100 women were followed prospectively (15 of whom were breastfeeding at entry). While it was a small study, there was no difference in mean change in LVEF from entry to 12 months. While it is a small study, there was not even a signal towards an adverse effect with breastfeeding on myocardial recovery (graphic abstract below).
3. How should we approach patients with PPCM presenting with cardiogenic shock?
- Note, our usual inotropic agents can still be used in pregnant patients.
- There have been case series of successful use of mechanical support as a bridge to recovery or durable VAD for PPCM patients.
- In one review, pregnant patient on VA-ECMO tended to have better outcomes than other patients who require this form of support. This difference is more pronounced if you look at pregnant patients with cardiac cause for decompensation. Their survival approaches 80% with fetal survival of 65%.
- Complications of cardiogenic shock are similar those in nonpregnant patients. However with shock in a pregnant patient, we also need to factor in timing and mode of delivery as well as anticipated bleeding with delivery. It is important that management is a discussion across a multi-disciplinary Cardio-Ob team caring for the patient.
4. What are the cornerstones of management for PPCM patients?
- GDMT: most heart failure medications are considered safe in breastfeeding patients and beta blockers are a cornerstone of therapy (except atenolol). There is no data on ARNI in breastfeeding women yet.
- ACEi/ARB/MRA/Sacubitril-Valsartan/Ivabradine should not be used during pregnancy.
- You may use hydralazine/nitrates for afterload reduction in pregnancy.
- Anticoagulation should be considered postpartum with LVEF < 35%.
- For patients with PPCM who would typically qualify for an ICD, the general expert consensus experts is to wait longer before placing a device, as there is a high rate of myocardial recovery in the first 6-12 months after diagnosis. An option for these patients is a wearable defibrillator, however, keep in mind that there are logistical challenges with breastfeeding while wearing a defibrillator.
5. What are predictors for recovery and what’s important to remember in follow-up for these patients?
- Low LVEF at diagnosis (particularly LVEF <30%), LV dilatation, and RV involvement are associated with poor prognosis.
- PPCM disproportionately affects African American women in the US who also have lower rates of recovery and higher morbidity and mortality.
- In the IPAC study, 70% of patients achieved myocardial recovery (LVEF >50%) by 1 year following diagnosis. However, none of the patients with both LVEF < 30% and LV > 6 cm at presentation recovered to normal LVEF. For those who do not recover normal cardiac function, studies show nearly 50% will go on to further deterioration with a subsequent pregnancy and are at the highest WHO classification risk for pregnancy.
- Progesterone-releasing subcutaneous implants are first line for contraception, but likely all contraceptive methods have a benefit which outweighs potential risks of a subsequent pregnancy with abnormal baseline cardiac function.
Koczo A, Marino A, Jeyabalan A, Elkayam U, Cooper LT, Fett J, Briller J, Hsich E, Blauwet L, McTiernan C, Morel PA, Hanley-Yanez K, McNamara DM; IPAC Investigators. Breastfeeding, Cellular Immune Activation, and Myocardial Recovery in Peripartum Cardiomyopathy. JACC Basic Transl Sci. 2019 Jun 24;4(3):291-300.
Olson TL, O’Neil ER, Ramanathan K, Lorusso R, MacLaren G, Anders MM. Extracorporeal membrane oxygenation in peripartum cardiomyopathy: A review of the ELSO Registry. Int Cardiol. 2020 Jul 15;311:71-76.
Goland S, Modi K, Bitar F, Janmohamed M, Mirocha JM, Czer LS, Illum S, Hatamizadeh P, Elkayam U. Clinical profile and predictors of complications in peripartum cardiomyopathy. J Card Fail. 2009;15:645–650. doi: 10.1016/j.cardfail.2009.03.008
Dr. Julie Damp is program director of the cardiology fellowship at Vanderbilt University. She was part of the multicenter Peripartum Cardiomyopathy Network for the Investigations in Pregnancy-Associated Cardiomyopathy (IPAC) Study. In addition to her clinical and research work in cardio-obstetrics, her expertise include medical education, critical care cardiology, and noninvasive cardiac imaging.
Dr. Agnes Koczo is a second year cardiology fellow at the University of Pittsburgh Medical Center. She is interested in cardio-obstetrics and adult congenital heart disease. She plans to pursue a T32 postdoctoral research fellowship studying immune dysregulation in patients with cardiac complications in pregnancy.
Dr. Loie Farina @loiefarina is a cardiology fellow at Northwestern University. After venturing down south for undergrad at Duke (go Blue Devils!), she returned home to Chicago and has since completed both medical school and residency at Northwestern. She hopes to pursue a career in advanced heart failure and transplantation and is passionate about medical education and heart disease in women. Outside the hospital, she enjoys running along Chicago’s Lakefront Trail, cooking, and exploring new restaurants.