Abstract
The complex interplay between pregnancy and cardiovascular disease is not fully understood. The 1st International Congress on Cardiac Problems in Pregnancy held in Valencia, Spain, gathered experts from multiple disciplines to discuss the complex interactions between pregnancy and the cardiovascular system, from both the maternal and fetal perspective. Important questions were discussed and our gap in knowledge highlighted, with an emphasis on the need for further research in this important area of medicine.
Pregnancy is a wondrous example of the mammalian capacity for biological adaptation. From the point of conception forward, maternal organ systems undergo rapid physiological and functional change in order to meet the challenges of providing for the gestating fetus. Perhaps no other organ system undergoes as much change and adaptation as does the cardiovascular system. Circulating blood volume increases, systemic vascular resistance decreases, and cardiac performance is pushed to its limits as demands incrementally increase. Maternal cardiac output increases by up to 50%, with associated increases in ventricular wall muscle mass, end-diastolic volume and cardiac compliance, resulting in the maintenance of ejection fraction. In some patients, these physiological changes negatively impact the normal heart, with the development of clinical phenomena such as preeclampsia or cardiomyopathy, during or soon after pregnancy. Furthermore, in patients with known heart ailments, such as survivors of congenital or valvular heart disease, the imposition of pregnancy can lead to serious complications and may have deleterious long-term consequences.
In order to improve our understanding of the effects of pregnancy on the cardiovascular system, scientists and clinicians gathered at the 1st International Congress on Cardiac Problems in Pregnancy (CPP) in Valencia, Spain. The event is the culmination of efforts by Uri Elkayam (University of Southern California School of Medicine, CA, USA) and Avraham Shotan (Israel), important thinkers and generators of literature on the medical intersections of pregnancy and cardiovascular disease. The gathering was a remarkable achievement in bringing together a disparate, multidisciplinary group of attendees. Experts from the realms of adult cardiology, obstetrics, maternal–fetal medicine, anesthesiology, congenital heart disease and fetal cardiology were brought together to exchange perspectives and knowledge. Topics covered included cardiac evaluation of the pregnant woman, preconception evaluation, fetal heart disease, drugs in pregnancy and lactation, peripartum cardiomyopathy, thromboembolic complications during pregnancy, management of the pregnant mother with valvular or congenital heart disease, pulmonary hypertension and cardiac anesthesia and surgery during pregnancy.
Before pregnancy: preconception evaluation & counseling
Principles of preconceptual counseling for the patient with heart disease includes timely availability of a broad range of consultants, patient understanding of the nature and severity of the cardiac condition, an estimate of the risk of adverse events, and plans for surveillance and care during and after pregnancy. Samuel Siu (Mount Sinai Hospital, University of Toronto, Canada) developed a method for the characterization and assessment of preconception risk Citation[1,2]. Poor functional status (New York Heart Association [NYHA] class >II) or cyanosis, left ventricular systolic dysfunction, left heart obstruction and history of cardiac events prior to pregnancy (arrhythmia, stroke or pulmonary edema) are predictors of maternal cardiac complications. These are components of a risk index that have been prospectively validated. Pregnancies with zero, one, or more than one predictors correspond to a low, high or intermediate risk level, respectively. Cardiac conditions in which pregnancy should be avoided include pulmonary vascular obstructive disease, Marfan syndrome with aortopathy and peripartum cardiomyopathy with residual left ventricular dysfunction.
What is the nature of these types of counseling encounters? Ruth Brooks et al. (University College London Hospitals, London, UK) reviewed their experience with a preconception counseling service. Of 116 referrals, 49 had inherited heart disease, 51 congenital and 16 acquired heart disease. Of 40 women with moderate or highly complex disease, 15% were advised not to conceive pending further investigations and of these, two were advised to have cardiac interventions (one aortic valve replacement and one mitral valvuloplasty). One woman with an ejection fraction of 15% and pulmonary hypertension was counseled for a very high risk of death, and unfortunately died prior to completing the evaluation process.
Pregnancy & congenital heart disease
Complex congenital heart disease poses risks of pregnancy-related cardiac complications, including arrhythmia, stroke, heart failure and death. Pregnancy worsens maternal cyanosis by reducing afterload, which exacerbates right-to-left shunting. Cyanosis results in increased fetal loss, prematurity and low birthweight. Risk increases with worse maternal hypoxia, with most fetuses lost in the first trimester if oxygen saturation is less than 85%.
I Ananaba (Houston, TX, USA) reported on 27 patients with 32 pregnancies; maternal diagnosis was transposition of the great vessels in 22% and tetralogy of Fallot in 19%. Systemic ventricular function was depressed in 13%. Maternal outcomes were notable for worsening NYHA functional class II or greater in 13% and symptomatic arrhythmia in 16%. D Born (São Paulo, Brazil) reported on 154 pregnancies in women with congenital heart disease. In comparison to patients with acyanotic heart defects, mothers with cyanosis had higher rates of preterm delivery (55 vs 12%; p = 0.002), lower birthweight (64 vs 14%; p < 0.005) and smaller for gestational age infants (36 vs 8%; p = 0.02). For the most complex forms of congenital heart disease, such as single ventricle and hypoplastic left heart syndrome after Fontan operation, pregnancy is possible with careful attention and observation for onset of maternal complications Citation[3]. Raquel Prieto and colleagues (University College London Hospitals, London, UK) reported on the outcome of 25 pregnancies in ten women with single ventricle and Fontan circulation. All were NYHA class II prior to pregnancy. There were 16 miscarriages and nine live births. Of the live births, the mode of delivery was cesarean section in six and vaginal in three; mean gestational age was 35.8 weeks (range: 34–38 weeks). Early delivery was for obstetrical reasons in four and cardiac in two. There were no maternal or fetal deaths. Maternal complications included heart failure in one, supraventricular tachycardia in one and pulmonary embolism in one; obstetric complications consisted of placental abruption in one, and subchorionic hematoma in a patient on low-molecular weight heparin (LMWH).
Can pregnancy result in lingering complications in those with congenital heart disease? Dominica Zentner and colleagues (Royal Melbourne Hospital, Melbourne, Australia) studied 15 pregnant women with a systemic right ventricle postatrial switch for transposition of the great arteries and compared them with age match-controlled women who did not get pregnant and looked at progression of right ventricular dysfunction and tricuspid regurgitation over a period of 10 years. These investigators found moderate or greater right ventricular dysfunction, moderate or greater tricuspid regurgitation, and a larger right ventricle size were more likely in those who were pregnant, suggesting an accelerated deterioration in systemic ventricular performance in this population.
Anticoagulation & pregnancy
One of the most engaging aspects of the CPP Congress was a debate between Carol Warnes and Andra James concerning the optimal strategy for anticoagulation in pregnant women with mechanical prosthetic valves Citation[4]. Warfarin is the preferred agent for anticoagulation from the maternal perspective; however, it crosses the placenta and carries substantial fetal risk. Based on various reports, warfarin is associated with a 15–56% chance of miscarriage, up to 33% chance of congenital birth defects, 58% risk of being small for gestational age and a 14% risk of adverse neurological outcome. LMWH is an alternative, however thromboembolism with well-monitored administration of warfarin during pregnancy occurs in less than 2%, whereas the risk of thromboembolism with LMWH is as high as 10–20%. In addition, bleeding with LMWH is a common complication contributing to morbidity and mortality for both mother and fetus. While monitoring of anti-Factor Xa levels is the traditional laboratory method for evaluating the efficacy of LMWH, serious questions are raised as to the validity and utility of this assay during pregnancy, as wide fluctuations in values are common Citation[5]. P Soma-Pillay and colleagues (Pretoria, South Africa) found a correlation between warfarin dose and maternal/fetal outcomes, and recommend the use of no greater than 5 mg of warfarin daily as the optimal dose. Alternative strategies for anticoagulation include the use of LMWH early in pregnancy and then switching to warfarin after the first trimester, or perhaps even concluding that the risks are too great and encouraging surrogate pregnancies for such patients. Consensus was reached in agreeing that much more study is necessary before clear recommendations can be made for optimal anticoagulation of the pregnant woman with a prosthetic valve.
Cardiovascular disease in the fetus
The ability to assess the fetal cardiovascular system in exquisite detail currently exists. Boris Tutschek (Düsseldorf University, Germany) and Simcha Yagel (Hadassah-Hebrew University Medical Centers, Jerusalem, Israel) discussed the latest technical advances in fetal echocardiography Citation[6]. 3D ultrasound provides additional information and enhances our understanding of complex heart anomalies Citation[7]. Yagel further discussed the importance of evaluating the variability in venous anatomy that exists in the fetus, with particular attention needing to be paid to the fetal portal and hepatic venous systems.
Many abstracts focused on the relationship between congenital heart disease and neurocognitive deficits. Perinatal factors such as altered cerebral blood flow patterns, associated structural abnormalities of the CNS, or perhaps maternal stress-related elevations in cortisol inherent in a prenatal diagnosis of heart disease may contribute to these findings. E Mlczoch (Vienna, Austria) described fetal brain MRI findings in 68 fetuses with congenital heart disease and found 46% to have cerebral abnormalities. A Sarajuuri and colleagues (Helsinki, Finland) reported on the neurodevelopmental follow-up of fetuses with a univentricular heart at 30 months of age and found psychomotor development to be delayed, as well as neurological impairment in 23% patients with hypoplastic left heart syndrome.
Cardiovascular risks were described for monochorionic twin pregnancy, in which twin–twin transfusion syndrome (TTTS) exists Citation[8]. This disorder is considered a placental vasculopathy, whereby abnormal chorionic vascular connections between the twin fetal circulations are present. The donor twin is hypovolemic and secretes vasoconstrictive agents to maintain perfusion, while volume and vasoconstrictive agents cross into the recipient twin resulting in a cardiomyopathic response that includes ventricular dilation, hypertrophy and dysfunction. A cardiovascular score specific to this disorder (TTTS score) has been developed, which includes assessment of domains in the recipient such as:
• Ventricular characteristics
• Vascular assessment of atrioventricular valve inflow, ductus venosus and umbilical vein
• Atrioventricular valve regurgitation
• Great vessel analysis to look for the development of right ventricular outflow tract obstruction, a hallmark of this disease
And in the donor:
• Umbilical arterial flow abnormalities suggesting elevated placental vascular resistance
The TTTS score describes disease severity and is decreased in response to therapeutic maneuvers such as selective laser photocoagulation of placental vascular anastomoses.
Conclusion
The 1st International CPP Congress was exceptionally successful at breaking down conventional disciplinary barriers, which impede comprehensive and broad thinking about how best to manage the pregnant woman with heart disease. Bringing together various disciplines in this manner can stimulate collaborative focus on answering important questions. One quite obvious conclusion from the Congress was the need for generating a greater body of evidence-based knowledge from which to develop practice care models for the pregnant woman with heart disease. The enthusiasm generated by the 1st CPP Congress will motivate the development of new research endeavors, whose findings will continue to be shared at subsequent CPP Congresses in the future.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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