Practical practice points
1. Data on the long-term outcomes of women with heart disease following pregnancy are few, and are mostly based on small cohort studies or case reports.
2. Ventricular function and/or aortic valve regurgitation may worsen in some cases with subclinical or mild prior dysfunction.
3. Tissue valve prostheses may degenerate more rapidly during pregnancy.
4. Women with Marfan syndrome or aortic dilatation secondary to bicuspid valve and other aortopathies may experience more rapid dilatation during pregnancy.
Very few data exist with regard to the long-term outcome for women with heart disease, even before the superimposed hemodynamic burden of pregnancy is considered. With the declining incidence of rheumatic heart disease in North America and Western Europe, most maternal cardiac disease is now congenital in origin. Because of the significant advances in surgical intervention, diagnostic imaging, and treatment modalities, there have been dramatic changes in the lives of patients born with congenital heart disease (CHD) since the middle of the last century. Adult survivors, both men and women, represent a population growing at a rate of about 5% per year. Issues of ventricular dysfunction, arrhythmias, and valvar and vascular dysfunction are common and these patients require continuing care for their complex residua and sequelae. Patients with profoundly complex anatomy who would not have survived in the 1980s are now presenting to cardiology clinics after having had innovative and complex surgical repairs. In many cases, the long-term outcomes are unknown, and there are no postoperative historical comparisons with which to compare. Women who had previously been physiologically ill-equipped to bear children or who would not, in all probability, have reached reproductive age, are now presenting for obstetric and cardiac care after earlier and more sophisticated cardiac surgery.
The interplay between the pregnancy-related adjustments in maternal circulatory and respiratory physiology and the growth of the fetus is complex and the factors relating to pregnancy outcomes are many and variable. Most of the published reports regarding pregnancy and maternal cardiac disease of any sort focus on whether the outcome of pregnancy was successful for the fetus and whether the mother experienced any complications during the pregnancy or shortly thereafter. There are few if any data regarding the impact of pregnancy months or even years after delivery.
While normal pregnancy does not appear to have a deleterious effect on cardiac function in either the short or long term in women with normal cardiac anatomy, women with heart disease have less cardiac reserve and are thus more vulnerable. Although they often have a successful delivery and survive without major morbidity, there may be subtle changes in ventricular function or valve regurgitation that do not return to normal after delivery. These, in turn, may cause a gradual deterioration in exercise capacity over the ensuing months and years. When symptoms eventually develop, it is difficult, indeed impossible without proper comparative studies, to attribute the deterioration to the pregnancy rather than to the natural history of the cardiac problem. With the advances of noninvasive imaging since the 1990s, particularly two-dimensional echocardiography, it is now possible to serially follow changes in ventricular size and function, valvar abnormalities, and aortic dimensions. This has facilitated the ability to determine the impact, positive or negative, of a therapeutic intervention, for example, or a hemodynamic burden such as pregnancy.
This chapter will focus on four cardiac problems in which pregnancy has now been recognized as having a possible detrimental effect on maternal well-being and long-term outcome.
Patients who have mild impairment of ventricular function frequently have at least mild atrioventricular (AV) valve regurgitation. The hemodynamic changes that take place during a normal pregnancy include a 40–50% increase in plasma volume, a HR increase of 10–20%, and a fall in systemic and pulmonary vascular resistance.[1–6] The increased cardiac output necessary to sustain a pregnancy results in mild increases in cardiac chamber dimensions that have been documented by echocardiography.[7,8] These may affect the right-sided cardiac chambers slightly more than the left. Chamber enlargement can cause annular dilatation, and minor alterations in the geometry of the ventricles can impair effective coaptation of the AV valves. Once AV regurgitation occurs, this adds to the circulatory burden on the ventricles and tends to beget more AV valve regurgitation. These changes may be irreversible.
When the underlying cardiac anatomy is abnormal, not only are the baseline hemodynamics often impaired, but the changes imposed by pregnancy are likely to be more profound. This has been demonstrated in women whose systemic ventricles have right ventricular morphology, the so-called “systemic right ventricle” (i.e. those with transposition of the great arteries after atrial switch procedures [Mustard or Senning operations]). Guedes et al. reviewed 16 women who had 28 pregnancies and monitored their clinical status and echocardiographic parameters before, during, and after pregnancy. These women were all in New York Heart Association (NYHA) functional class I (n=21) or II (n=7) before pregnancy. The functional class deteriorated in six women (38%) with no return to prepregnancy levels after delivery in two. Two of the 16 women required heart failure therapy during or soon after pregnancy. Echocardiographic parameters in relation to the right (systemic) ventricular dimensions and function and tricuspid regurgitation were reviewed before, during, and after pregnancy. Data on right ventricular dimensions were available for 18 pregnancies: right ventricular dilatation was absent (n=4), mild/moderate (n=12), or severe (n=2), and progressed in five women (31%) with no recovery in any during a follow-up period of 24 months. Data on right ventricular function were available in 21 pregnancies: before pregnancy, dysfunction was absent (n=16), mild/moderate (n=4), or severe (n=1). Systolic dysfunction progressed in four women (25%) with no recovery in three cases. Tricuspid regurgitation was absent (n=8), mild (n=9), or moderate (n=3) before pregnancy and deteriorated in eight women (50%) with no recovery in three women.
This study underscores the progression and deterioration of hemodynamic changes during pregnancy in these women with complex anatomy. While it is possible that they could be attributable to the natural history of the anomaly, the short time frame involved makes that explanation unlikely. This is one of the very few studies to evaluate serial echocardiographic parameters before and during pregnancy and for several months after delivery. It is certainly possible that such changes in ventricular dimensions and function and secondary AV valve regurgitation might be seen in other maternal cardiac disease (for example single ventricle physiology), particularly when ventricular function is borderline or mildly reduced prepregnancy. Whether any form of stress testing prepregnancy might delineate impaired cardiac reserve remains to be determined. This decline in ventricular function was not observed in another small study, however, in which 53 patients with CHD had a clinical and echocardiographic evaluation before and 1.5 years after pregnancy. Both NYHA functional class as well as left ventricular size and function remained unchanged compared with an age-matched control group. Pregnancy was associated with a persistent increase in the size of the right ventricle in patients with repaired tetralogy of Fallot, however, and this was not seen in the control patients, although the numbers were fairly small. This may relate to the somewhat greater increase in size of the subpulmonary (right) ventricle compared with the left ventricle in pregnant women with normal hearts (20% vs 6%); perhaps patients with tetralogy of Fallot who have an already compromised right ventricle at baseline may be more vulnerable to the volume load that pregnancy imposes.
Many women who have had an episode of peripartum cardiomyopathy subsequently normalize their ventricular function, and a common question is whether or not it is advisable for them to have another pregnancy.[11–13] The evidence suggests that a subsequent pregnancy may be associated with recurrent left ventricular dysfunction in approximately 30%; this is sometimes persistent and associated with symptomatic heart failure. Rarely, profound clinical deterioration and even death may occur. It has been suggested that the hemodynamic changes of pregnancy unmask subclinical myocardial dysfunction, or perhaps there is a reactivation of the underlying hemodynamic process responsible for the development of cardiomyopathy in the previous pregnancy. Unfortunately, there is no consensus on appropriate advice regarding the advisability of future pregnancy after a single episode of peripartum cardiomyopathy. However, the evidence that a persistent reduction in ventricular function can occur with a subsequent pregnancy should be shared with the woman and her family at the time of prepregnancy counseling [11,16], and they should be advised to give serious consideration to the option of avoiding further pregnancies.
Marfan syndrome is one of the most common hereditary connective tissue disorders and is associated with an abnormal fibrillin-encoding gene (FBN1) located on chromosome 15.[17–19] Marfan syndrome can be associated with many cardiovascular complications, including aortic, dissection, and rupture. Pregnancy increases the risk of dissection, particularly when there is a family history of aortic dissection, and some women may have significant acceleration of aortic dilatation with or without aortic regurgitation. The exact mechanism is unclear, although the hyperdynamic circulation and increase in volume load associated with pregnancy may be contributory. The published data, however, represent a bias toward reporting the complications of pregnancy, because uncomplicated cases tend not to be reported. Those women with mild aortic root dilatation prepregnancy (<40 mm) sometimes have no increase in the rate of aortic dilatation compared with women with Marfan syndrome who have never been pregnant.[20,21] This is somewhat unpredictable, however, and even women with Marfan syndrome and a normal aortic size can develop dissection or other serious cardiac complications with an incidence of approximately 1%. This means that during pregnancy close surveillance is necessary, even in women with no previous cardiovascular problems. The prophylactic use of beta-adrenergic receptor blockade may be beneficial but this is unproven because there have been no large prospective randomized trials. Some patients with Marfan syndrome also have mitral valve prolapse and varying degrees of mitral regurgitation: this too may progress with the volume load of pregnancy, but long-term data are lacking. Certainly, the possibility of progression of both valvar and aortic complications should be discussed with the prospective mother at the time of preconception counseling.
Structural abnormalities of the great arterial walls in patients with CHD are an increasing focus of attention.[23–26] The association of the bicuspid aortic valve with aortic medial abnormalities has been known for decades, and the loss of smooth muscle cells and degeneration of the elastic medial fibers—the so-called “cystic medial necrosis,” which in some ways resembles the histological appearance of Marfan syndrome—is well described.[25,27,28] The presence of a bicuspid aortic valve is associated with aortic dilatation even in the setting of a functionally normal valve.[29,30] A bicuspid aortic valve increases the propensity to aneurysm formation and increases the risk of dissection at least ninefold.
While bicuspid aortic valves have not been found to be associated with any specific chromosomal abnormality, patients have been shown to have significantly less fibrillin-1 in their aortic media compared with their counterparts with tricuspid aortic valves. Whether pregnancy causes further aortic dilatation in women who already have a dilated aortic root is uncertain, but estrogen has been shown to inhibit collagen and elastin deposition in the aorta, and progestogen has been reported to accelerate deposition of noncollagenous proteins in the aortas of rats. In addition, it has been reported that pregnancy may be accompanied by fragmentation of elastic fibers, a decrease in mucopolysaccharides, and an increase in smooth muscle. Whether these gestational changes are additive to the underlying histological abnormality is uncertain. Aging and the presence of systemic hypertension can produce similar histological abnormalities. Several other heritable disorders affect the thoracic aorta, rendering patients vulnerable to aneurysm formation, dissection, and rupture. These include Ehlers- Danlos syndrome, Turner syndrome, Loeys-Dietz syndrome, and familial forms of aortic dissection.
Because of these concerns, recommendations similar to those for Marfan syndrome are often applied to women with other aortopathies at the time of prepregnancy counseling. Thus, women who have an aortic root dimension of >40 mm should be informed of the potential for further aortic dilatation, aneurysm formation or even dissection, although this is based more on general principles rather than on the evidence of published data. In the presence of a bicuspid aortic valve, however, dissection occurs less frequently than in Marfan syndrome, but when the aortic root is 50 mm or larger, prepregnancy operation should be considered. Other aortopathies such as Ehlers–Danlos type IV, Loeys-Dietz and Turner syndromes have a much higher risk of aortic catastrophe, and prophylactic surgery is recommended when the aorta is 45 mm or greater. While the approach must be individualized, many consider these heritable disorders to be contraindications to pregnancy. Women with coarctation of the aorta (a common association of bicuspid aortic valve) are also known to have an aortopathy,[24,25] and they too may experience further aortic dilatation during pregnancy. However, there have been no reports of sequential imaging studies and long-term outcome data after pregnancy are lacking.