Pericarditis Management in Pregnancy

 Quick Takes

• Pericarditis affects pregnant women similar to age-matched controls.
• Most cases of pericarditis during pregnancy can be managed medically with careful consideration of the impact of medications on the developing fetus.

Introduction

Pericarditis is an important medical problem that affects women of reproductive age. While the frequency of pericarditis in pregnancy is not known, pregnancy does not appear to impact the epidemiology or etiology of the disease. Based on case series in the literature, pericardial disease, including pericarditis, occurs with similar frequency in pregnant patients as in age-matched controls.^1,2 The evaluation of a pregnant woman with suspected pericarditis should be similar to the non-pregnant patient. Most cases of pericarditis in pregnancy, including recurrent, are idiopathic. The majority of cases can be managed medically. Treating pregnant women with pericarditis involves careful discussion of risks and benefits of different therapeutics to make patient-centered decisions regarding medical therapy. Timing of therapy and dosage of medication should be discussed as indications for therapy and choice of treatment may vary across gestational ages.

Table 1

Safety of medications pre-conception, during pregnancy, and while breastfeeding. Courtesy of Pryor K, Tartar L, Economy K, Weber B.

Management

The current evidence on management is limited, and no formal guidelines exist for the management of pericardial disease in pregnancy. Multiple case reports and several case series inform management of pericarditis in pregnancy. The largest study is a report of 21 pregnancies in 14 women with a history of recurrent idiopathic pericarditis.³ Another recent case series prospectively followed 12 pregnant women (14 pregnancies) with active pericarditis.⁴ Based on the data available from these and larger studies regarding medication use in pregnancy, the following approach is reasonable:

• Women with chronic pericarditis planning pregnancy should be counseled to achieve disease control ideally for 6 months prior to conception.
• Non-steroidal anti-inflammatory drugs (NSAIDs) are a cornerstone of management of pericarditis in pregnant women, in the first and second trimesters, but should be stopped before the third trimester to prevent premature closure of the ductus arteriosus.⁵ There is some controversy regarding periconception NSAID use. While some data say it is acceptable, others suggest it may be associated with impaired ovulation and higher rates of miscarriage.⁶ Patients attempting to conceive on NSAIDs should review their plan with their cardiologist and obstetrician-gynecologist to best assess the risks and benefits. Low dose aspirin may be continued throughout conception and into the postpartum period. NSAIDs are also compatible with breastfeeding. Ibuprofen is preferred due to reduced cross-placental transfer and shorter half-life.⁷ Non-selective NSAIDS are favored over the COX-2 selective agents given limited data in pregnancy and breastfeeding with the latter.^7,8
• Colchicine is an adjunctive therapy that decreases rates of recurrent pericarditis (an off label indication for use in the United States[US]), and may be beneficial given that recurrent pericarditis can be seen intra- and post-partum.³ Colchicine was previously flagged as a potential teratogen given its anti-mitotic properties and higher rates of both miscarriage and malformations in animal studies, albeit with doses substantially higher than those used in humans. However, in recent years, reassuring data have emerged supporting safety in pregnancy, predominantly from studies of Familial Mediterranean Fever, a condition frequently treated with chronic daily colchicine. Its safe use during conception, pregnancy and breastfeeding is supported by the 2020 American College of Rheumatology reproductive health guidelines.^8-10
• Restriction of strenuous physical activity while under treatment for pericarditis is recommended by both consensus groups in the US as well as the European Society of Cardiology. While evidence from studies is limited, activity restriction may decrease the risk of complications including the development of pericardial effusion, recurrent or refractory symptoms, or the progression to myocarditis.¹¹ Return to activity in pregnant patients can follow the same general guidelines applied to non-pregnant patients, which typically includes the gradual introduction of exercise once patients do not have evidence of activity disease (including normalization of inflammatory markers without fevers, and absence of pericardial effusion).^11,12

Management of Incessant/Recurrent/Refractory Pericarditis

• Glucocorticoids: Glucocorticoids are often effective when NSAIDs and colchicine have not adequately controlled symptoms and can be safely used during conception and pregnancy. Glucocorticoids should be nonfluorinated, typically prednisone or prednisolone, as their rapid metabolism limits fetal exposure. Prednisone, or equivalent, dosing should ideally be ≤20mg/day to limit trans-placental passage; this dose is also considered safe in breastfeeding.⁸ Women on high dose steroids may require stress dose steroids in labor.
• IL-1 receptor antagonists: In cases of recurrent/refractory pericarditis, there are insufficient data on the use of IL-1 receptor antagonists (IL-1Ra) during pregnancy to make a recommendation for use. Case reports and cohort studies, predominantly of patients with cryopyrin-associated periodic fever syndromes, are not able to address whether or not adverse outcomes are secondary to IL-1Ra or to pregnancy in the setting of underlying inflammatory disease. Given this ambiguity, these medications should be discontinued at conception and avoided throughout pregnancy.^13,14 While data in breastfeeding are limited, use during breastfeeding is conditionally recommended.^8,15
• Azathioprine, Intravenous Immunoglobulin (IVIG): Although evidence for benefit in pericarditis is limited, both azathioprine and IVIG are safe in pregnancy and breastfeeding.⁸
• Methotrexate, Mycophenolate Mofetil: While only rarely used to treat recurrent or refractory pericarditis outside of pregnancy, both methotrexate and mycophenolate mofetil (MMF) are contraindicated in pregnancy. Patients attempting conception should discontinue methotrexate 1-3 months prior to conception, and MMF at least 6 weeks prior to conception.⁸ Both medications should be avoided during breastfeeding.

Conclusion

Pericarditis can be safely and successfully treated during pregnancy and breastfeeding with a targeted approach. Appropriate care of women pre-conception, antepartum and postpartum is essential in optimizing maternal and fetal outcomes. Collaboration with a maternal fetal medicine specialist and a rheumatologist can be beneficial.

References

Katherine Pryor, MD; Laura Tartar, MD; Katherine Economy, MD; Brittany 

1. Serati L, Carnovale C, Maestroni S, et al. Management of acute and recurrent pericarditis in pregnancy. Panminerva Med 2021;63:276-87.
2. Brucato A, Imazio M, Curri S, Palmieri G, Trinchero R. Medical treatment of pericarditis during pregnancy. Int J Cardiol 2010;144:413-14.
3. Brucato A, Pluymaekers N, Tombetti E, et al. Management of idiopathic recurrent pericarditis during pregnancy. Int J Cardiol 2019;282:60-65.
4. Lotan D, Wasserstrum Y, Itelman E, Nir-Simchen M, Arad M, Kuperstein R. Management and outcome of acute and recurrent pericarditis during pregnancy. Eur Heart J 2020;41;ehaa9452157.
5. Koren G, Florescu A, Moldovan Costei A, Boskovic R, Moretti ME. Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis. Ann Pharmacother 2006;40:824-29.
6. Li DK, Liu L, Odouli R. Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study. BMJ 2003;327:368.
7. Birru Talabi M, Clowse MEB. Antirheumatic medications in pregnancy and breastfeeding. Curr Opin Rheumatol 2020;32:238-46.
8. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 2020;72:529-56.
9. Indraratna PL, Virk S, Gurram D, Day RO. Use of colchicine in pregnancy: a systematic review and meta-analysis. Rheumatology (Oxford) 2018;57:382-87.
10. Ben-Chetrit E, Scherrmann JM, Levy M. Colchicine in breast milk of patients with familial Mediterranean fever. Arthritis Rheum 1996;39:1213-17.
11. Grant JK, Shah NP. The impact of physical activity on pericarditis. Curr Cardiol Rep 2021;23:150.
12. Shah N, Phelan DMJ. Physical Activity Recommendations in Patients With Acute Pericarditis. http://www.acc.org. Feb 09, 2017. Accessed 2/20/2022. https://www.acc.org/latest-in-cardiology/articles/2017/02/09/07/24/physical-activity-recommendations-in-patients-with-acute-pericarditis.
13. Brien ME, Gaudreault V, Hughes K, Hayes DJL, Heazell AEP, Girard S. A systematic review of the safety of blocking the IL-1 system in human pregnancy. J Clin Med 2021;11:225.
14. Youngstein T, Hoffmann P, Gul A, et al. International multi-centre study of pregnancy outcomes with interleukin-1 inhibitors. Rheumatology (Oxford) 2017;56):2102-08.
15. Drugs and Lactation Database (LactMed) [Internet] (https://www.ncbi.nlm.nih.gov/). 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501871/. Accessed 02/20/2022.

The Increasing Role of Rhythm Control in Atrial Fibrillation

The  following are key points to remember about the increasing role of rhythm control in patients with atrial fibrillation (AF):

1. AF management comprises three main domains summarized in the “ABC” scheme of the 2020 European Society of Cardiology AF guidelines; these are “A” for anticoagulation/avoid stroke, “B” for better symptom control using rate and rhythm management, and “C” for therapy of concomitant cardiovascular conditions.
2. PIAF, AFFIRM, RACE, AF-CHF, STAF, and J-RHYTHM are the key trials that have shown few significant differences in important endpoints between rhythm- and rate-control strategies. In AFFIRM and RACE, there was a trend towards a higher mortality for rhythm control compared with rate control. As a result of these trials, treatment currently defaults to initial rate control, with rhythm control being reserved to improve symptoms that persist despite adequate rate control.
3. Antiarrhythmic drugs (AADs) approximately double the likelihood of maintaining sinus rhythm compared with no rhythm-control therapy. AF ablation (pulmonary vein isolation) has been shown to be more effective than AADs in maintaining sinus rhythm, including when used as first-line treatment for rhythm control, and with a good safety record (RAAFT, RAAFT-2, STOP AF, EARLY-AF, and CRYO-First trials). However, ablation should not be seen as a one-off curative treatment for AF.
4. The use of “upstream” therapies (such as mineralocorticoid receptor antagonists, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and sodium-glucose co-transporter-2 inhibitors) has also been shown to be associated with improved maintenance of sinus rhythm.
5. Lifestyle adjustments such as weight loss, increased exercise, and the management of sleep apnea may also lead to reduction in AF burden.
6. Dronedarone is associated with a better safety profile and is thus supported as a first-line treatment option for rhythm management in some patient populations. The ATHENA trial showed that treatment with dronedarone reduced the risk of a primary outcome of hospitalization due to unexpected cardiovascular events or death from any cause compared with placebo.
7. In the CASTLE-AF trial, catheter ablation was associated with a reduced AF burden and an improved left ventricular ejection fraction compared with pharmacological treatment in patients with coexisting AF and heart failure.
8. The EAST-AFNET 4 study in patients with AF diagnosed within 12 months before altering the view on early rhythm control as a general treatment concept. The first primary outcome was a composite of death from cardiovascular causes, stroke (ischemic or hemorrhagic), or hospitalization with worsening heart failure or acute coronary syndrome, which was reduced by 21% in patients assigned to early rhythm control compared with usual care. The primary safety outcome was not different between randomized groups. Compared with those assigned to usual care, the occurrence of stroke was reduced by approximately one-third and total mortality was 16% lower in patients randomized to early rhythm control. These data showed a consistent beneficial effect of early rhythm control versus usual care, independent of whether the patient was symptomatic or asymptomatic. The use of amiodarone and dronedarone as AAD options in EAST-AFNET 4 and the availability of AF ablation in patients who failed AAD therapy may have contributed to this outcome given that they can be safely used in patients with structural heart disease.
9. Results from the ATTEST trial showed that early ablation as part of standard care was superior to AAD therapy alone in delaying progression from recurrent paroxysmal AF to persistent AF, with the effect apparent at 1 year of follow-up and maintained over 3 years.
10. There is an active search for more effective and safer AADs such as small conductance calcium-activated potassium (SK) channel inhibitors, TWIK-related acid-sensitive potassium channel (TASK-1) inhibitors, slow sodium channel inhibition and multichannel inhibitors, and alternative ablation approaches such as pulsed field ablation or electroporation.

ACC.