Position Statement on COVID-19 and Pregnancy in Women with Heart Disease Department of Women Cardiology of the Brazilian Society of Cardiology – 2020

Celi Marques-Santos Walkiria Samuel Avila Regina Coeli Marques de Carvalho Alexandre Jorge Gomes de Lucena Claudia Maria Vilas Freire Elizabeth Regina Giunco Alexandre Felipe Favorette Campanharo Maria Alayde Mendonça R. Rivera Maria Elizabeth Navegantes Caetano Costa Marildes Luiza de Castro About the authors

1. Background

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) on March 11, 2020.11. World Health Organization. (WHO) Coronavirus disease (COVID-19) Pandemic. [Cited in 2020 Apr 23] Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
https://www.who.int/emergencies/diseases...

COVID-19 has a high transmissibility and a variable symptom presentation, ranging from asymptomatic or mild symptoms to critical conditions.22. Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z, et al. Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). Version 2. J Gen Intern Med. 2020 May;35(5):1545-9. Its mild symptoms include dry cough, sore throat, dyspnea, gastrointestinal symptoms, fatigue, anosmia, ageusia, and headache, while serious events include thromboembolism and cardiovascular complications.33. Li L, Huang T, Wang Y, Wang Z, Liang Y, Huang T et al. COVID-19 Patients’ Clinical Characteristics, Discharge Rate, and Fatality Rate of Meta-Analysis. J Med Virol. 2020 Jun; 92(6):577-83. Approximately 10% of the patients may present pneumonia and progress to acute respiratory distress syndrome (ARDS), multiple organ failure, and death.44. Weiss P, Murdoch DR. Clinical course and mortality risk of severe COVID-19. Lancet. 2020 Mar 28; 395(10229):1014-5.

Epidemiological evidence strongly suggested that pregnant women had a higher risk of serious illness and death from viral infections during the previous epidemics of H1N1 influenza55. Meljer WJ, van Noortwijk AG, Bruinse HW, Wensing AM. Influenza virus infection in pregnancy. A review. Acta Obstet Gynecol Scand. 2015 Aug; 94(8):797-819. and two other diseases caused by coronaviruses: SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome).66. Rabaan AA, Al-Ahmed SH, Haque S, Sah R, Tiwari R, Malik YS, et al. SARS-CoV-2, SARS-CoV, and MERS-COV: A Comparative Overview Infez Med. 2020 Jun 1; 28(2):174-84. The WHO thus considered that pregnant women should be considered at risk for COVID-19.

Thereafter, the Brazilian Ministry of Health included pregnant and postpartum women, along with those that had miscarriages, in the high-risk COVID-19 group.77. Brasil. Ministério da Saúde. Secretaria de Atenção Especializada à Saúde. Protocolo de manejo clínico da Covid-19 na Atenção Especializada. [Citado em 2019 dez 12]. Disponível em: https://portalarquivos.saude.gov.br/images/pdf/2020/April/14/Protocolo-de-Manejo-Clínico-para-o-Covid-19.pdf
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The high mortality of COVID-19 when associated with chronic diseases such as heart disease, diabetes mellitus, and arterial hypertension is also worth noting.88. Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q et al. Prevalence of Comorbidities and Its Effects in Patients Infected With SARS-CoV-2: A Systematic Review and Meta-Analysis. Int J Infect Dis. 2020 May; 94: 91-5.,99. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020;323(20):2052-9.

Undoubtedly, a pregnant patient with heart disease who is suspected or confirmed for COVID-19 presents a clinical challenge, since the overlapping of complications could greatly increase maternal mortality.

Therefore, a statement on COVID-19, pregnancy, and heart disease is required at the current moment of this pandemic. The aims of this document are to exhibit aspects of COVID-19 during pregnancy when accompanied by heart diseases and propose recommendations that can contribute to protocols on the care of pregnant women with heart disease during this pandemic.

2. COVID-19 and Pregnancy

2.1. Maternal Outcome

Current evidence indicates that pregnancy is a risk factor for COVID-19.1010. Phoswa W, Khaliq OP. Is Pregnancy a risk fator of Covid-19? Eur J Obstet Gynecol 2020.06.058 Defining an outcome of this infection in pregnant women is difficult due to limitations in case experiences so far. In addition, global differences in public health policies, as well as cultural and socioeconomic conditions, hamper conclusions about the prognosis of pregnant women with SARS-CoV-2.1111. Santos DSS, Menezes MO, Andreucci CB, Nakamura-Pereira et al Disproportionate impact of COVID-19 among pregnant and postpartum Black Women in Brazil through structural racism lens. In press.

The Brazilian Ministry of Health, as of May 2020, had registered a high mortality in a cohort of 288 pregnant women with ARDS caused by COVID-19, most of whom were in their second or third trimesters. Data included 36 (12.5%) maternal deaths, with a high prevalence of heart disease among their co-morbidities (Table 1).1212. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde: Boletim Epidemiológico Especial, COE-COVID 19 - Semana Epidemiológica. (21 fevereiro, 2020) Disponível em: https://saude.gov.br.
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The most frequent signs and symptoms presented by pregnant women with COVID-19 were similar to those found in the general population, and oxygen desaturation was more frequent in patients who died (Figure 1).1212. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde: Boletim Epidemiológico Especial, COE-COVID 19 - Semana Epidemiológica. (21 fevereiro, 2020) Disponível em: https://saude.gov.br.
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Figure 1
Symptoms and outcome (cure or death) of pregnant women with COVID-19 respiratory distress syndrome.1313. Brasil. Ministério da Saúde. Sistema de Informação da Vigilância Epidemiológica da Gripe, SIVEP Gripe. (24 maio, 2020) Disponível em: https://sivepgripe.saude.gov.br/.
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Table 1
Outcome of pregnant women with COVID-19 respiratory distress syndrome according to gestational age and comorbidities1313. Brasil. Ministério da Saúde. Sistema de Informação da Vigilância Epidemiológica da Gripe, SIVEP Gripe. (24 maio, 2020) Disponível em: https://sivepgripe.saude.gov.br/.
https://sivepgripe.saude.gov.br/...

Considering the current COVID-19 pandemic, questions arise in the care of these patients concerning the continuation of pregnancy, choice of ideal delivery route, possibility of vertical viral transmission, isolation of the neonates, and breastfeeding advisement.

2.2. Obstetrical and Fetal Outcomes

No conclusive data currently indicate fetal damage in pregnant woman with SARS-CoV-2 infection.1414. Knight M, Bunch K, Vousden N, Morris E, Simpson N, Gale C, et al. UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Group Characteristics and Outcomes of Pregnant Women Admitted to Hospital With Confirmed SARS-CoV-2 Infection in UK: National Population Based Cohort Study. BMJ. 2020 jun 08;369; doi: 10.1136/bmj.m2107.
https://doi.org/10.1136/bmj.m2107...
In a systematic review including 43 pregnant women with COVID-19, the only reported complications were a higher rate of preeclampsia and perinatal complications such as preterm birth.1515. Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R, Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol MFM. 2020;2(2):100118.

The route of birth depends on obstetric reasons and clinical urgency. Vaginal delivery is not contraindicated, considering that there is no convincing evidence of vertical transmission. A reasonable labor duration and the safest delivery route should be individualized irrespective of SARS-CoV-2 infection. 1616. Poon LC, Yang H, Kapur A, et al. Global interim guidance on coronavirus disease 2019 (COVID- 19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professional. Int J Gynecol Obstet 2020;149(3): 273-86 In critically ill parturients (with hypoxia, cardiovascular or neurological complications, or signs of progressive multiple organ failure), a cesarean section is the most appropriate route of birth.1717. Schnettler WT, Al Ahwel Y, Suhag A. Severe ARDS in COVID-19-infected Pregnancy: Obstetric and Intensive Care Considerations. Am J Obstet Gynecol. 2020 Apr 14;2(3):100120

2.3. Perinatal Transmission

Expression of the ACE2 receptor has been reported in the placenta, particularly in the villous cytotrophoblast and syncytiotrophoblast cells. This means that the mother could be in higher risk of contracting SARS-CoV-2 and that transmission from mother to child could occur.1010. Phoswa W, Khaliq OP. Is Pregnancy a risk fator of Covid-19? Eur J Obstet Gynecol 2020.06.058 However, the perinatal transmission of SARS-CoV-2 is still controversial.1818. Fan C, Lei D, Fang C, Li C, Wang M, Liu Y, et al. Perinatal transmission of COVID_19 associated SARS-Cov2: Should we worry? Clin Infect Dis.2020 Mar 1y.ciaa226. Online. ahead of print.

Out of 75 neonates of mothers with COVID-19, only 1 tested positive for the disease; clinical evolution was satisfactory, with slight changes in liver enzymes. Among babies with COVID-19, studies reported lymphocytopenia, radiological findings of pneumonia, and one case of disseminated intravascular coagulation; all children reached full recovery. From these findings, we cannot exclude neither a sub-clinical response to the mother's infection displayed by the fetus and newborn, nor transplacental vertical transmission.1919. Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl Pediatr. 2020; 9(1):51-60. Therefore, close monitoring of newborns whose mothers are infected with COVID-19 is recommended.

Breast milk is the best nutrition source for newborns and infants, including those whose mothers have a confirmed or suspected coronavirus infection.2020. Fernández-Carrasco FJ, Vázquez-Lara JM, González-Mey U, Gómez-Salgado J, Parrón-Carreño T, Rodríguez-Díaz L. Coronavirus Covid-19 Infection and Breastfeeding: An Exploratory Review. Rev Esp Salud Publica. 2020 May; 94. PMID: 32458823. To date, SARS-CoV-19 has not been detected in breast milk. An analysis of 114 infected mothers and their newborns detected antibodies against SARS-CoV-2 (considered a protective factor against infection) in breast milk and concluded that breastfeeding should not be interrupted. Thus, breastfeeding is recommended, provided that mothers follow appropriate measures of respiratory hygiene and according to WHO recommendations.2121. World Health Organization (WHO). Covid-19 and breastfeeding. Position paper. [Cited in 2020 april 08] Available from: https://www.euro.who.int/__data/assets/pdf_file/0010/437788/breastfeeding-COVID-19.pdf.
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On the other hand, if the mother's health does not allow direct breastfeeding, breast milk must be previously collected and kept unpasteurized. Milk banks could be used in order to ensure feeding of the newborn.

Considering that our experience with SARS-CoV-2 infection during pregnancy is still limited, further studies are necessary to better evaluate maternal and fetal risks and the effects of COVID-19 on pregnant patients.

3. Pregnancy, Heart Disease, and COVID-19

3.1. Physiological Changes of Pregnancy that Induce Cardiovascular Complications by COVID-19

During pregnancy, changes in coagulation and immune, respiratory, and cardiovascular systems are determinant factors that induce complications leading to maternal death from all causes (Table 2). Throughout this period, the immunological system2222. Zenclussen AC. Adaptive immune responses during pregnancy. Am J Reprod Immunol. 2013 Apr; 69(4): 291-303. triggers an attenuation of the immunity mediated by Th1 cells due to a physiological change into a predominantly Th2 environment, which contributes to an increasing maternal susceptibility to intracellular pathogens and virus infections and general maternal morbidity.2323. Liu H, Wang L, Zhao S, Kwak-Kim J, Mor G, Liao A. Why Are Pregnant Women Susceptible to COVID-19? An Immunological Viewpoint. J Reprod Immunol. 2020 Jun;139:103122. The Th1-type cytokines include proinflammatory interleukins (IL-1a, IL-1b, IL-6, IL-12) and interferon-g (IFN-g), while Th2-type cytokines are anti-inflammatory interleukins (IL-4, IL-10, IL-13) and transforming growth factor β (TGF-β). Patients with SARS displayed preferential activation of Th1 immunity, resulting in a marked elevation of proinflammatory cytokines for at least two weeks after disease onset and severe lung damage.2424. Saito S, Nakashima A, Shima T, Ito M. h1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010 Jun; 63(6): 601-10. Even though patients with COVID-19 demonstrated activation of both Th1 and Th2 immunities, culminating with the presence of IFN-g and IL-1b, in addition to IL-4 and IL-10, high levels of IL-6 (a predominantly Th1-type response) are associated with an increased risk of mortality.

Table 2
Impact of physiological changes in the cardiovascular and respiratory systems of pregnant women with cardiac disease and SARS-CoV-2 infection.

The respiratory system undergoes an adjustment during pregnancy due to hormonal influences and the mechanical effects of increasing uterine volume, resulting in a progressive decrease in total lung capacity and chest wall compliance.2525. Hegewald MJ. Respiratory physiology in pregnancy. Clin Chest Med. 2011; 32(1):1-13. For these reasons, COVID-19 pneumonia may have a rapid and progressive evolution, from focal consolidation to diffuse and bilateral destruction of the pulmonary parenchyma and severe respiratory failure. Cases of maternal hypoxia resulting from impaired ventilation and gas exchange could reduce placental perfusion, ultimately resulting in fetal distress and even death.

The activation of the coagulation system is characteristic of a healthy pregnancy and involves the synthesis of coagulation factors II, VII, VIII, IX, and X, as well as fibrinogen, in addition to a reduction in endogenous anticoagulants (especially antithrombin and protein S); these determine the state of hypercoagulability.2626. Cui C, Yang S, Zhang J, Wang G, Huang S, Li A, et al. Trimester-specific coagulation and anticoagulation reference intervals for healthy pregnancy. Thromb Res. 2017;156:82-6. These changes happen progressively after the first trimester with a shortening of prothrombin, partial thromboplastin, and thrombin times that weakens anticoagulant function . When adding to these mechanisms the mechanical compression of the venous plexus on the lower limbs by the gravid uterus, a predisposition to thromboembolism during pregnancy is justified.

The cardiovascular system suffers a hemodynamic overload during pregnancy that may aggravate the functional state of underlying heart diseases. Cardiac output progressively increases in the first trimester, reaching its highest at the beginning of the third trimester. Simultaneously, peripheral vascular resistance (not limited to the uterine plexus) decreases in a greater magnitude than the elevation in cardiac output.2727. Sanghavi M, Rutherford JD. Cardiovascular physiology of pregnancy. Circulation. 2014;130(12):1003-8.

3.2. Pregnancy and Heart Disease Bring a High Risk for COVID-19

Since pregnant women with heart disease are at risk for serious cardiac complications, it is mandatory that health care professionals obtain the required knowledge to reduce mortality in this high-risk cohort of patients.2828. Pfaller B, Sathananthan G, Grewal J, Mason J, D'souza R, Spears D, et al. Preventing Complications in Pregnant Women With Cardiac Disease. J Am Coll Cardiol. 2020 Mar 31;75(12):1443-52.

In Brazil, rheumatic heart disease is the main etiology of heart diseases encountered during pregnancy, followed by congenital heart diseases and cardiomyopathies. Reports of maternal outcomes show that around 25% of pregnant women had cardiovascular complications (including heart failure, thromboembolism, and arrhythmias) as the main causes of hospitalization and maternal mortality.2929. Avila WS, Rossi EG, Ramires JAF, Grinberg M, Bortolotto MRL, Zugaib M et al. Pregnancy in Patients with Heart Disease: Experience with 1,000 Cases. Clin. Cardiol. 2003;26(3):135-42.,3030. Campanharo FF, Cecatti JG, Haddad SM, Parpinelli MA, Born D, Costa ML et al. The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil. Plos One. 2015;10(12):e0144385.

It is worth mentioning that pregnant women with congenital heart disease belong to a special group of patients because of their great diversity in anatomical and functional changes. The anatomical cardiac defects range from mild defects, which do not present additional risk when compared to healthy pregnant women, to complex heart abnormalities that result in very high and even prohibitive risks, especially cyanosis and pulmonary hypertension.

Therefore, a risk stratification of pregnancy in women with heart disease is essential to estimate the prognosis and to plan prevention and treatment strategies for possible complications.3131. Avila WS, Alexandre ERG, Castro ML, Lucena AJG, Marques-Santos C, Freire CMV, et al. Brazilian Cardiology Society Statement for Management of Pregnancy and family Planning in women with Heart Disease-2020- Arq Bras Cardiol. 2020;114(5):849-942. The most accepted risk estimation method proposed for pregnancy is the modified WHO classification, which is divided into four risk categories (Table 3).3232. Balci A, Sollie-Szarynska KM, van der Bijl AG, Ruys TP, Mulder BJ, Roos-Hesselink JW, et al. Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with congenital heart disease. Heart. 2014;100 (17):1373-81.

Table 3
Classification of maternal cardiovascular risk: World Health Organization (mWHO)

4. Overlapping Complications of Covid-19, Pregnancy, and Heart Disease

4.1. Differential Diagnosis

Confirmation of COVID-19 diagnosis is essential. The similarity between its clinical characteristics and those of the pregnant woman with heart disease can delay diagnosis and postpone protective measures against its spread (Table 4).22. Jiang F, Deng L, Zhang L, Cai Y, Cheung CW, Xia Z, et al. Review of the Clinical Characteristics of Coronavirus Disease 2019 (COVID-19). Version 2. J Gen Intern Med. 2020 May;35(5):1545-9.,33. Li L, Huang T, Wang Y, Wang Z, Liang Y, Huang T et al. COVID-19 Patients’ Clinical Characteristics, Discharge Rate, and Fatality Rate of Meta-Analysis. J Med Virol. 2020 Jun; 92(6):577-83.,1212. Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde: Boletim Epidemiológico Especial, COE-COVID 19 - Semana Epidemiológica. (21 fevereiro, 2020) Disponível em: https://saude.gov.br.
https://saude.gov.br...
,3333. Soma-Pillay P, Nelson-Piercy C, Tolppanen H, Mebazaa A. Physiological Changes in Pregnancy. Cardiovasc J Afr. 2016;27 (2):89-94. Therefore, considering the current pandemic, tests for SARS-CoV-2 should be included as good practice in the universal screening of pregnant women with heart disease.

Table 4
The COVID-19/heart disease/pregnancy triad: features and differential diagnosis

4.2. Impact of COVID-19 on the Cardiovascular System of Pregnant Women

The current COVID-19 pandemic has resulted in thousands of deaths due to severe systemic inflammation and multiple organ failure. The cardiovascular system is also affected by this disease, resulting in complications such as myocardial injury, myocarditis, acute myocardial infarction, heart failure, arrhythmias, and thromboembolic events.3434. Atri D, Siddiqi HK, Lang JP, Nauffal V, Morrow DA, Bohula EA. COVID-19 for the Cardiologist. Basic Virology, Epidemiology, Cardiac Manifestations and Potential Therapeutic Strategies. JACC Basic to translation Science. 2020;55(5):518-36.,3535. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and Cardiovascular Disease. Circulation.2020;141(20):1648-55.

Within this topic, an important subject to be considered is the pivotal role of the angiotensin-converting enzyme 2 (ACE2) in COVID-19 cardiovascular complications.3636. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-7. ACE2 is found on the surface of lung alveolar epithelial cells (considered the entry site for SARS-CoV-2) and catalyzes the cleavage of angiotensin II, a proinflammatory factor. This imbalance in immune regulation, in addition to an increased metabolic demand and procoagulant activity, are responsible for the increased risk of adverse outcomes in patients with COVID-19-related cardiovascular disease.3737. Crackower MA, Sarao R, Oudit GY. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417(6891):822-8.

However, recent research has suggested that the virus may also cause direct damage to the heart utilizing ACE2 receptors in the cardiac tissue.3838. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA. 2020 Mar 27;5(7):1-8. The prevalence of cardiovascular disease in COVID-19 patients is still unclear, but preexisting heart disease may be associated with more severe COVID-19 outcomes.

4.2.1. Myocardial Injury, Myocarditis, and Heart Failure

Among the mechanisms of acute myocardial injury caused by the SARS-CoV-2 infection, the following stand out: the expression of ACE2 in the cardiovascular system, a cytokine storm triggered by an unbalanced autoimmune response, and hypoxemia resulting from ARDS. 3434. Atri D, Siddiqi HK, Lang JP, Nauffal V, Morrow DA, Bohula EA. COVID-19 for the Cardiologist. Basic Virology, Epidemiology, Cardiac Manifestations and Potential Therapeutic Strategies. JACC Basic to translation Science. 2020;55(5):518-36.3737. Crackower MA, Sarao R, Oudit GY. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417(6891):822-8.

An extreme inflammatory response to COVID-19 can result in endothelial injury, myocarditis, and ventricular dysfunction, with symptoms of chest pain, dyspnea, and palpitation.3838. Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA. 2020 Mar 27;5(7):1-8. These symptoms overlap with the usual complaints of pregnant women with heart disease, making the diagnosis of heart failure during pregnancy even more difficult.

Peripartum cardiomyopathy should always be considered when cardiac decompensation occurs in the last months of pregnancy or following delivery in previously healthy women.3939. Bauersachs J, Konig T, van der Meer P, Petrie MC, Hilfiker-Kleiner D, Mbakwem A, et al. Pathophysiology, diagnosis and management of peripartum cardiomyopathy: a position statement from Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy. Eur J Heart Fail. 2019; 21(9): 827-43 When symptoms such as exhaustion, chest pain, or fatigue (which usually occur in late pregnancy and postpartum periods) are not given appropriate attention, a delay in the diagnosis of peripartum cardiomyopathy may occur and the patient could have a worse prognosis and less chance of myocardial systolic function recovery. Therefore, prompt diagnosis of this disease is crucial for patient survival4040. Ng AT, Duan L, Win T, Spencer HT, Lee MS. Maternal and fetal outcomes in pregnant women with heart failure. Heart. 2018;104(23):1949-54. and physicians should be aware of the differential diagnosis of pregnancy-related dyspnea, COVID-19, and heart failure from peripartum cardiomyopathy for efficient decision-making.3131. Avila WS, Alexandre ERG, Castro ML, Lucena AJG, Marques-Santos C, Freire CMV, et al. Brazilian Cardiology Society Statement for Management of Pregnancy and family Planning in women with Heart Disease-2020- Arq Bras Cardiol. 2020;114(5):849-942.,4141. Melo MA, Carvalho JS, Feitosa FE, Araujo Júnior E, Peixoto AB, Costa Carvalho FH, et al. Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome. Rev Bras Ginecol Obstet. 2016; 38(6): 308-13. A specific algorithm for managing patients and the establishment of a multidisciplinary team is crucial in these cases.

Pulmonary edema is also seen in healthy women as a consequence of major changes in intravascular volume during labor and after delivery. Similarly, hemodynamic changes during pregnancy increase the gradient through the stenotic mitral valve and cause pulmonary congestion. Patients with congenital cyanotic heart disease, left heart obstructive lesions, or severe systolic ventricular dysfunction are at increased risk. A reduction in systemic vascular resistance worsens hypoxemia in patients with pulmonary hypertension and complex congenital heart disease.2828. Pfaller B, Sathananthan G, Grewal J, Mason J, D'souza R, Spears D, et al. Preventing Complications in Pregnant Women With Cardiac Disease. J Am Coll Cardiol. 2020 Mar 31;75(12):1443-52.3030. Campanharo FF, Cecatti JG, Haddad SM, Parpinelli MA, Born D, Costa ML et al. The Impact of Cardiac Diseases during Pregnancy on Severe Maternal Morbidity and Mortality in Brazil. Plos One. 2015;10(12):e0144385.

4.2.2. Hypercoagulable State and Thrombotic Events

Disorders of the coagulation system are a critical aspect of morbidity and mortality in COVID-19. The disease has been associated with inflammation and a prothrombotic state, with increases in fibrin, fibrin degradation products, fibrinogen, and D-dimer.4242. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 118(4):844-7. In this context, it is assumed that the combination of COVID-19, pregnancy,4343. Makatsariy AD, Slukhanchuk EV, Bitsadze VO, Khizroeva JKH, Tsibizova VI. Thrombotic microangiopathy, DIC-syndrome and COVID-19: link with pregnancy prothrombotic state J Thromb Haemost. 2020 Apr; 18(4): 786–787. and heart conditions such as the use of mechanical valve prostheses or atrial fibrillation in rheumatic mitral valve disease greatly increases the risk of arterial thromboembolism, demanding a rigorous anticoagulation protocol.4444. Tang N, Bai H, Chen X, Bai H, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. Mar 27 2020;18(5):1094-9,4545. Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020 Jun 4;135(23):2033-40.

Notably, D-dimer is a prothrombotic biomarker used as an exclusion criterion of pulmonary thromboembolism, but its usefulness during pregnancy has limitations. Its levels increase progressively and significantly through pregnancy and peak in the third trimester, making it important to consider that D-dimer levels are above the conventional cut-off (500 μg/L) in 99% of healthy pregnant women.4646. García IG, Cañadas PP, Uriarte JM, Izquierdo OG, Pérez MAJ, Romualdo LGG. D-dimer During Pregnancy: Establishing Trimester-Specific Reference Intervals. Scand J Clin Lab Invest. 2018 Oct;78(6):439-42. Doi: 10.1080/00365513.2018.1488177.
https://doi.org/10.1080/00365513.2018.14...

Recently, the pregnancy-adapted YEARS algorithm proposed that the diagnosis of pulmonary embolism during pregnancy could be safely ruled out in the absence of these three parameters: (1) clinical signs of deep vein thrombosis; (2) hemoptysis; and (3) pulmonary embolism as the most likely diagnosis and D-dimer level < 1000 ng/mL. However, the D-dimer cut-off for pregnant women with COVID-19 is still unknown. Hence, the use of noninvasive tools such as venous duplex scans and echocardiographies is encouraged in the search for the correct diagnosis of thromboembolism or cardiac events. These bedside examinations are highly available, present low costs, and can be repeated if needed.4747. van der Pol LM, Ttomeur C, Bistervels IM, Aile FNi; van Bemmel, Berloetti L et al. Pregnancy-Adapted YEARS Algorithm for Diagnosis of Suspected Pulmonary Embolism N Engl J Med.2019;380:1139-49

4.2.3. Proinflammatory Condition and Vascular Damage

The systemic inflammation and coagulopathy exhibited by COVID-19 increase the risk of atherosclerotic plaque rupture and acute myocardial infarction.3434. Atri D, Siddiqi HK, Lang JP, Nauffal V, Morrow DA, Bohula EA. COVID-19 for the Cardiologist. Basic Virology, Epidemiology, Cardiac Manifestations and Potential Therapeutic Strategies. JACC Basic to translation Science. 2020;55(5):518-36.,3535. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and Cardiovascular Disease. Circulation.2020;141(20):1648-55. The release of inflammatory cytokines can cause a reduction in coronary blood flow and oxygen supply, plaque destabilization, and microthrombogenesis. The significant implication of the SARS-CoV-2 infection becomes evident with acute myocardial injury with high results of highly sensitive troponin assays4848. Lippi G, Lavie CJ, Sanchis-Gomar F. Cardiac Troponin I in Patients With Coronavirus Disease 2019 (COVID-19): Evidence From a Meta-Analysis. Prog Cardiovasc Dis. May-Jun 2020;63(3):390-391. and/or new electrocardiogram and echocardiogram abnormalities, complex cardiac arrhythmias, and cardiac arrest. On the other hand, the occurrence of acute coronary syndrome during pregnancy is not common,4949. Tripathi B, Kumar V, Pitiliya A, Arora S, Sharma P, Shah M, et al. Trends in Incidence and Outcomes of Pregnancy-Related Acute Myocardial Infarction (From a Nationwide Inpatient Sample Database). Am J Cardiol. 2019;123(8):1220-7. even though infections (especially in the postpartum period) are among the risk factors for myocardial infarction. It is important to emphasize that the most frequent causes of myocardial infarction during pregnancy are spontaneous coronary artery dissection,5050. Cade J R; Szarf G, Siqueira MEM, Chaves A, Andréa JCM, Figueira H R Pregnancy-associated spontaneous coronary artery dissection: insights from a case series of 13 patients Journal - Cardiovascular Imaging. 2017 Jan;18(1):54-61. followed by atherosclerosis, coronary thrombosis, and angiographically normal arteries with impaired coronary microcirculation. So far, no data has been published on myocardial infarctions in pregnant patients with COVID-19.

4.2.4. Proinflammatory Condition, Hypoxemia, and Myocardial Injury Induce Arrhythmias

Finally, arrhythmias may be present in patients with COVID-19, with multiple simultaneous causes such as inflammation, hypoperfusion, fever, or hypoxia. Still, normal pregnancies present electrical cardiac disturbances that increase the incidence of maternal cardiac arrhythmias, ranging from clinically irrelevant isolated premature beats to debilitating supraventricular and ventricular tachycardias.5151. Vaidya VR, Arora S, Patel N, Badheka AO, Patel N, Agnihotri K; et al. Burden of Arrhythmia in Pregnancy. Circulation. 2017;135(6):619-21. The occurrence of arrhythmias during pregnancy requires investigation with special attention to identifying or excluding structural cardiac lesions, electric cardiac injury, and general infections. This is a fundamental step when determining the treatment and prognosis of arrhythmias, particularly those with iatrogenic causes amid the COVID-19 pandemic. Under these conditions, the impact of COVID-19 therapy on QT prolongation can be verified on the Tisdale Risk Score (https://www.mdcalc.com/tisdale-risk-score-qt-prolongation).5252. Tanindi A, Akgun N, Pabuccu EG, Gursoy AY, Yüce E, Tore HF, et al. Electrocardiographic P-Wave duration, QT interval, T peak to End Interval and Tp-e/QT Ratio in Pregnancy With Respect to Trimesters. Ann Noninvasive Electrocardiol. 2016 Mar;21(2):169-74.

5. Summary and Conclusions

Pregnant women with heart disease are a high-risk group for COVID-19 mortality. The knowledge of overlapping complications between pregnancy and COVID-19 allows the establishment of preventive measures according to cardiac risk stratification. Therefore, early diagnosis of SARS-CoV-2 infection is of crucial importance and the routine use of SARS-CoV-2 testing is fundamental for pregnant women with heart disease . Potential benefits of these good practices include early diagnosis and determination of isolation practices, including guidance on the use of personal protective equipment and neonatal care.

The establishment of a specialized routine provides an important opportunity to protect mothers, babies, and health care professionals during these difficult times. Data on the COVID-19 pandemic are constantly being published and the following recommendations will certainly be reviewed and updated as new scientific information becomes available.

6. Recommendations for Pregnant Women with Heart Disease During the COVID-19 Pandemic (See Algorithm)

  1. Maintain a strict multidisciplinary follow-up at short intervals, according to the WHO risk stratification and maternal and fetal conditions;

  2. Maintain the administration of drugs prescribed for the treatment of heart disease, with necessary dose adjustments throughout the pregnancy;

  3. Reinforce information on forms of transmission, signs and symptoms, and prevention strategies for COVID-19 during prenatal visits;

  4. Avoid contact of all pregnant women over 24 weeks with patients in the COVID-19 area;

  5. Contact the patient in case of absence at a scheduled prenatal appointment;

  6. Advise seeking medical care at a referral service if the patient has any suspected COVID-19 symptoms or worsening of heart disease conditions;

  7. Conduct a standard investigation for COVID-19 in suspected cases, with an immediate indication for hospitalization if there is evidence of hemodynamic impairment and/or severity of the viral infection;

  8. Recommend self-isolation and monitoring for 14 days to patients with mild COVID-19 symptoms and stable cardiac and obstetric conditions;

  9. Hospitalization at initial assessment for suspected COVID-19 if O2 saturation ≤ 95%, regardless of symptom severity;

  10. Carefully judge the clinical deterioration due to COVID-19 and that resulting from cardiac disease;

  11. Perform imaging tests, when indicated, using abdominal protection to reduce exposure to radiation;

  12. Employ specific treatment for COVID-19 according to established protocols for different stages of the disease;

  13. Routinely perform RT-PCR tests for COVID-19 suspected cases and for all patients on admission for miscarriage or 48 hours before scheduled delivery;

  14. Consider B-type brain natriuretic peptide (BNP) and NT-proBNP as validated markers for the diagnosis of heart failure;

  15. Consider the influence of pregnancy on the D-dimer level as a biomarker for the diagnosis of pulmonary thromboembolism;

  16. Consider the Brazilian Cardiology Society Statement for Management of Pregnancy and Family Planning in Women with Heart Disease in the management of cardiovascular complications;

  17. Evaluate possible interactions between COVID-19 therapy and pregnancy using drug databases (www.drugs.com or www.crediblemeds.org);

  18. Advise close monitoring of newborns of mothers with COVID-19, since vertical transmission is still a possibility;

  19. Reinforce breastfeeding for postpartum women with COVID-19, if the health conditions of the mother and newborn allow it, with the following precautions: (1) The mother should practice respiratory hygiene during breastfeeding, which includes wearing a mask that covers the mouth and nose; and (2) Wash hands with soap and water for 20 seconds before and after breastfeeding;

  20. Evaluate possible interactions between COVID-19 therapy and breastfeeding using drug databases (www.drugs.e-lactancia.org);

  21. Suggest future pregnancy planning considering the control of the COVID-19 pandemic.

7. Algorithm


BNP: B-type natriuretic peptide; CRP: C-reactive protein; DVT: deep venous thrombosis; LDH: lactic dehydrogenase; NT-proBNP: N-terminal fragment of proBNP; RT-PCR: reverse transcriptase-polymerase chain reaction; § Table 4; §§ Table 3.

  • Development: Department of Women Cardiology of the Brazilian Society of Cardiology
  • Norms and Guidelines Council (2020-2021): Brivaldo Markman Filho, Antonio Carlos Sobral Sousa, Aurora Felice Castro Issa, Bruno Ramos Nascimento, Harry Correa Filho, Marcelo Luiz Campos Vieira
  • Norms and Guidelines Coordinator (2020-2021): Brivaldo Markman Filho
  • Statement Coordinators: Celi Marques-Santos, Walkiria Samuel Avila, Regina Coeli Marques de Carvalho
  • Writing Committee: Alexandre Jorge Gomes de Lucena, Claudia Maria Vilas Freire, Elizabeth Regina Giunco Alexandre, Felipe Favorette Campanharo, Maria Alayde Mendonça R. Rivera, Maria Elizabeth Navegantes Caetano Costa, Marildes Luiza de Castro
  • Note: These statements are for information purposes and are not to replace the clinical judgment of a physician, who must ultimately determine the appropriate treatment for each patient.

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Publication Dates

  • Publication in this collection
    07 Dec 2020
  • Date of issue
    Nov 2020
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