Aortopathy



Fig. 12.1
Aortic anatomy



Anatomically, the aorta is subdivided into four major segments: the ascending aorta – comprising the aortic root (including the annulus, sinuses of Valsalva, and sinotubular junction) – and the tubular ascending aorta, the aortic arch (segment of the aorta between the brachiocephalic artery and left subclavian artery), the descending thoracic aorta (extending from the isthmus between the origin of the left subclavian artery and ligamentum arteriosum to the diaphragm), and the descending abdominal aorta (extending from the diaphragm to the iliac bifurcation) [2] (Fig. 12.1).

Normal diameters of the aorta vary according to the location (tapering down going from the ascending to the descending part) and according to the individual’s gender and body surface area (BSA). Irrespective of BSA, women tend to have smaller aortas than men [3, 4]. With age, the aortic diameter increases at all segments with an average increase of 1 mm per decade for the ascending and descending thoracic aorta [5].

The aortic wall is histologically composed of three layers: a thin inner tunica intima lined by the endothelium; a thick tunica media characterized by smooth muscle cells embedded in an extracellular matrix and concentric sheets of elastic and collagen fibers, bordered by a lamina elastica interna and externa; and the outer tunica adventitia containing mainlyfibroblasts, collagen, vasa vasorum, and lymphatics [6].

The composition of the vessel wall varies according to the location: the abdominal aortic wall consists of fewer elastic lamellae, contains less structural proteins and has a lower elastin to collagen ratio when compared to the thoracic aorta [7].



12.1.2 The Diseased Aorta


Although more diseases are recognized, the two main conditions that we will consider in the scope of this chapter include aortic aneurysm and aortic dissection/rupture – the latter being consequences of preceding aortic aneurysm in many cases. Aortic aneurysm is defined as a permanent localized or diffuse dilatation of the aorta to at least 1.5 times its normal caliber and may affect the aortic root, tubular ascending aorta, aortic arch, and descending thoracic or abdominal aorta [2, 8]. Since pregnancy-related aortopathy is most commonly located in the thoracic aortic segments [9], we will further focus on thoracic aortic aneurysms and dissections (TAAD).

Aortic aneurysms will only occasionally lead to symptoms, related to local pressure, such as coughing, hoarseness, or swallowing difficulties. In most cases, however, thoracic aortic aneurysms (TAAs) will have an asymptomatic course and – if left undiagnosed or untreated – they can lead to dissection, an acute life-threatening event that is still associated with high mortality and morbidity rates. In thoracic aortic dissection (TAD), blood is diverted from its usual location within the lumen of the aorta into a false lumen within the media through a tear in the intima. The dissection can subsequently propagate both proximal and distal to the tear, hence affecting vital branching arteries and leading to coronary, cerebral, spinal, and/or visceral ischemia. Several classification systems for TAD exist, of which the Stanford classification is the most widely used. In Stanford type A dissection, the ascending aorta is involved, whereas type B dissection is typically located distally from the left subclavian artery. The distinction between both subtypes is relevant in view of important differences in prognosis and management. In aortic rupture, the tear in the aortic wall extends through all vessel layers, leading to life-threatening intrathoracic hemorrhage.

Due to its asymptomatic course, the exact incidence of thoracic aortic aneurysms is largely unknown. A recent contemporary, prospective cohort study of middle-aged individuals in Sweden reported an incidence rate of 9 per 100,000 patient-years (95 % CI 6.8–12.6) [10]. Estimating the incidence of acute aortic dissection is somewhat easier and has been studied more widely, but one has to bear in mind that a substantial proportion of aortic dissections may be left undiagnosed due to the high acute mortality rate of the disease. The incidence in the general population ranges from 2.6 to 4.7 per 100,000 person-years [11, 12]. The mortality rate associated with TAD reported a decade ago from the large International Registry of Aortic Dissections (IRAD) indicated that without urgent surgical intervention, type A dissection is associated with mortality rates as high as 20 % by 24 h and 40 % by day 7 [13]. Type B aortic dissections generally have a better outcome with a 30-day mortality rate of 10 %. Uncomplicated type B dissections are conventionally treated medically, whereas complicated type B dissections are treated using endovascular techniques or open surgery – results being comparable according to recent studies [14]. Despite advances in medical and surgical treatment options, mortality rates remain high, as demonstrated in a more recent prospective cohort study where the acute and in-hospital mortality was 39 % for aortic dissection and 41 % for ruptured TAD [10]. Women with aortic dissection typically present at an older age compared to men and display a higher hospital mortality and worse surgical outcome [15]. Etiological factors underlying TAAD include conventional cardiovascular risk factors although the lack of any significant association of TAA or AD with trends in smoking prevalence in a recent epidemiological study may suggest a difference in etiology compared with abdominal aortic aneurysms [8]. Differences in the pathogenesis of thoracic and abdominal aortic aneurysms may result from differences in aortic structures, biochemical properties, and origin of the vascular smooth muscle cells (VSMC) [16].

The underlying pathophysiology of TAAD has been widely studied, and many new insights have emerged from the study of monogenetic aortic diseases. These disease entities will be discussed in more detail below. Through human and mouse studies of monogenetic aortic diseases, it is now increasingly clear that aneurysms and dissections may result from alterations in structural, functional, and signal transduction properties in the wall of the aorta. The ensemble of these processes is referred to as altered mechanobiology and is illustrated in Fig. 12.2 and nicely reviewed by Humphrey and colleagues [46]. Based on these concepts, it is easy to conceive that dissections can be triggered by abnormalities in any of these processes: altered mechanical factors (hypertension, increased cardiac output, increased wall shear stress), alterations in structural components of the aortic wall (genetic defects in components of the elastic fibers), alterations in the signaling pathway (genetic defects in any component such as the TGFβ pathway), or altered signal transduction (genetic defects in extracellular matrix components, intracellular receptors, modulators).

A338684_1_En_12_Fig2_HTML.gif


Fig. 12.2
Concept of mechanobiology underlying homeostasis in the thoracic aorta and the possible effects of pregnancy. Mechanical force is sensed in the aortic wall and transmitted through the extracellular matrix to the intracellular molecular level. The signal is sensed by the smooth muscle cell contractile apparatus as well as by components of the TGFβ signaling pathway. Pregnancy affects the mechanical stimulus on the one hand and the elastic fibers in the extracellular matrix on the other hand. Alterations, either due to higher imposed forces (hypertension) or due to (genetic) alterations in the various components required for proper sensing and/or transduction of the signal, may lead to aneurysms/dissections. Genes involved in these pathways are listed at the bottom of the figure and are reported in Table 12.1 with their respective disorders



12.2 Pregnancy Outcomes


Since the first report on pregnancy-related aortic dissection in 1944 [47], over 80 additional reports have been published, most of them being case reports. A limited number of population-based studies and surgical series on the occurrence of aortic dissection have also been published, but caution is warranted when interpreting these results because of their heterogeneity with regard to design, study population, and diseases under study (type A vs. type B dissection).

Although the estimated incidence of aortic dissection during pregnancy is relatively low (0.05–1.39 per 100,000 person-years [48, 49] or 0.6 % per pregnancy [15]), the high maternal mortality rates (between 21 and 53 %) account for the high ranking in the list of maternal death causes [48, 5052]. The reported figures show some variation according to the country they are issued from. Aortic dissection ranks first on the list of mortality causes in the UK and the Netherlands, but is only the third cause of cardiovascular death in the French registry where three fatal dissections are reported during the period of 2007–2009, two out of these three being in women with Turner syndrome [53].

In women younger than 40 years of age, pregnancy has reportedly been associated with a significant increase in the risk for acute aortic dissection (with odds ratios for pregnancy up to 23 in one study [49]. Other studies however could not demonstrate a direct link between dissection and pregnancy [48]. A selective reporting bias may be invoked as a possible explanation for these discrepancies [54]. These data should be interpreted carefully, especially in women with underlying conditions, until large prospective studies assessing all aspects of a direct link are published. Data on aortic disease extracted from the large international registry on the outcome of pregnancy in patients with congenital heart disease are expected to be very valuable (the ROPAC study, see for more information at ​www.​escardio.​org/​Guidelines-&​-Education/​Trials-and-Registries/​Observational-registries-programme/​Registry-Of-Pregnancy-And-Cardiac-disease-ROPAC).

The risk for aortic dissection during pregnancy increases with gestational age, with most of the events occurring during the third trimester (55–78 %) [51, 55]. The majority of reported aortic dissections occurring during pregnancy (70 %) are type A aortic dissections [9], although type B aortic dissections seem to be more commonly reported in women with Marfan syndrome (see below).

In addition to the hemodynamic and hormonal changes occurring during pregnancy, the process of labor imposes substantial stress on the aorta and, hence, increases the risk for dissection. Uterine contractions, pain, stress, exertion, and bleeding, all impose an extra demand on the cardiovascular system [56]. The correct management of women at increased risk for dissection during labor in an experienced fetomaternal unit is, therefore, mandatory [57]. Follow-up of the aortic diameter and awareness of a possibly higher risk of aortic dissection should be considered until 6 months postpartum [51].


12.2.1 Predisposing Conditions


Several diseases are associated with increased aortic vulnerability, and affected women will therefore require special multidisciplinary care starting before pregnancy and extending well after delivery.


12.2.2 Heritable Thoracic Aortic Disorders: H-TAD


H-TAD is a heterogeneous group of disorders characterized by the common denominator of thoracic aortic disease (TAD) [58]. The presentation of aortic involvement varies widely from an incidental finding on an imaging study to fatal aortic dissection. The term “heritable” does not necessarily imply that all these disorders have a known genetic cause – despite significant advances in the genetic background of TAD, many patients and families do not harbor mutations in the genes identified so far. Based on the presence of additional clinical features in other organ systems, H-TAD can be further subdivided into syndromic and nonsyndromic forms. The spectrum of genes identified in these various clinical entities is highly variable. Genes can be grouped in those encoding components of the extracellular matrix, genes encoding components of the TGFβ signaling pathway, and genes encoding components of theVSMC contractile apparatus. An overview of the clinical conditions according to the currently known genetic defects with their respective typical clinical characteristics is provided in Table 12.1. Nearly all genes listed in this table can also be identified in patients with nonsyndromic forms of H-TAD.


Table 12.1
Overview of the syndromic forms of H-TAD with their respective genes and main clinical features. Genes are grouped according to the categories presented in Fig. 12.1





























































































 
Disorder

Gene(s)

Main cardiovascular features

Additional clinical features

ECM associated

Marfan [1720]

FBN1

Aortic root aneurysm, aortic dissection, mitral valve prolapse, main pulmonary artery dilatation, ventricular dysfunction, arrhythmia

Lens luxation, skeletal features (arachnodactylia, pectus deformity, scoliosis, flat feet, increased arm span, dolichocephalia)

Vascular Ehlers–Danlos [21]

COL3A1

Arterial dissections, middle-sized artery aneurysm

Translucent skin, dystrophic scars, facial characteristics

MFAP5 [22]

MFAP5

Aortic root dilatation, atrial fibrillation, mitral valve prolapse

Pectus deformities

Cutis laxa syndromes [23, 24]

FBLN4, ELN

Arterial aneurysms and dissections, arterial tortuosity, arterial stenoses, BAV

Hyperlax skin and joints, lung emphysema, craniofacial anomalies, bone fragility

TGFβ associated

Loeys–Dietz [25, 26]

TGFBR1/TGFBR2

Aneurysms and dissections of the aorta and middle-sized arteries, arterial tortuosity, mitral valve prolapse, congenital cardiac malformations

Bifid uvula/cleft palate, hypertelorism, marfanoid skeletal features

Aneurysm–osteoarthritis syndrome [2730]

SMAD3

Aneurysms and dissections of the aorta and middle-sized arteries, intracranial aneurysms, visceral and iliac artery aneurysms, arterial tortuosity, mitral valve prolapse, congenital cardiac malformations

Osteoarthritis, hypertelorism, marfanoid skeletal features

TGFB2 [3133]

TGFB2

Aortic root aneurysms and dissections, mitral valve prolapse, cerebrovascular disease

Marfanoid skeletal features

TGFB3 [3436]

TGFB3

Aortic root aneurysms

Marfanoid skeletal features, hypertelorism, muscle hypotonia, and congenital joint contractures

Shprintzen–Goldberg [37, 38]

SKI

Mild aortic root dilatation, mitral valve prolapse

Craniosynostosis, distinct craniofacial features, marfanoid skeletal features, mild-to-moderate intellectual disability

Juvenile polyposis [39]

SMAD4

Aortic root aneurysms, mitral valve prolapse, hereditary hemorrhagic telangiectasia

Juvenile polyposis, periventricular nodular heterotopia with seizures and joint hypermobility

Contractile unit associated

EDS-PH [40]

FLNA

Aneurysms of the aorta, pulmonary artery, and middle-sized arteries

Periventricular nodular heterotopia with seizures, joint hypermobility

ACTA2 [41, 42]

ACTA2

Thoracic aortic aneurysms and dissection, BAV, PDA, cerebrovascular disease, coronary artery disease

Livedo reticularis, iris flocculi

PRKG1 [43]

PRKG1

Aneurysms and dissection of the aorta and middle-sized arteries, arterial tortuosity
 

MYH11 [41, 44]

MYH11

PDA
 

MYLK [45]

MYLK

Thoracic aortic aneurysms and dissection

Gastrointestinal tract involvement


BAV bicuspid aortic valve, PDA patent ductus arteriosus


12.2.3 Marfan Syndrome


Marfan syndrome (MFS) is the prototype of syndromic H-TAD. MFS is caused by mutations in the fibrillin 1 gene (FBN1) and typically affects a myriad of organ systems including the ocular, the skeletal, and the cardiovascular systems. The clinical presentation is highly variable, both within and between families [1719, 59]. When considering the cardiovascular system, aortic aneurysms and dissections are the most common and life-threatening problems related to MFS. The risk for aortic dissection in MFS is significantly increased to 170 per 100,000 individuals per year (compared to 6 per 100,00 per year in the general population) [60]. Other cardiovascular manifestations related to MFS include mitral valve prolapse, subclinical cardiomyopathy, and arrhythmias [20, 6165].

The intrinsic aortic wall fragility associated with MFS along with the hemodynamic and hormonal changes occurring during pregnancy, as described above, gives rise to a higher risk for (fatal) dissection and aortic rupture in pregnant MFS women. Early publications, mostly case reports, on pregnancy in MFS showed a grim outcome with more than half of the cases ending with (fatal) aortic dissection. Most of the women in these earlier publications had preexistent severe cardiovascular disease, but based on these reports, patients were generally counseled against pregnancy [66]. A systematic assessment of pregnancy in MFS women was undertaken for the first time in 1981. Pyeritz and colleagues reviewed pregnancy-related cardiovascular risks in 26 patients with MFS and compared these to non-MFS women. Cardiovascular complications were not significantly different between both groups, but MFS women showed a higher rate of spontaneous abortion. Although no aortic diameters are reported in this study, the authors proposed an aortic root diameter of 40 mm before pregnancy as a threshold for stratifying women as having low risk (1 %) or increased risk (10 %) for dissection. Since then this stratification has been widely applied and debated in the literature [9, 6771], but remains a reference value in the current European guidelines for the management of cardiovascular diseases during pregnancy [55]. In these guidelines the modified WHO classification is applied to determine maternal risk, where MFS patients may fall under class II to IV: women with no aortic dilation are classified as WHO II, women with an aortic dilation between 40 and 45 mm are classified as WHO III, and women with an aortic diameter above 45 mm are classified as WHO IV.

The risk of aortic complications in MFS is not only present during pregnancy and delivery but also during the puerperium and even beyond pregnancy. Indeed the concerns about the long-term effect of pregnancy on aortic root growth, the incidence of dissection, and the need for elective aortic root replacement have been raised and need further assessment [72, 73].

Between 1995 and 2013, four prospective trials addressing pregnancy-related cardiovascular complications in MFS patients have been conducted – the main findings on pregnancy outcome in these women are illustrated in Fig. 12.3. A total of 97 women undergoing 149 pregnancies have been followed prospectively. Forty-two women in this combined cohort had an aortic root exceeding 40 mm prior to pregnancy, and five had undergone aortic root surgery prior to pregnancy [72, 7476].

A338684_1_En_12_Fig3_HTML.gif


Fig. 12.3
Cardiovascular outcome in MFS women during pregnancy (Data pooled from [72, 7476]). 1Two women with valve sparing surgery, three women with Bentall of which two after acute type A dissection, and 2two women with previous type A dissection 3needing AoR replacement 6 months after pregnancy

Three out of these four studies not only assessed the immediate effect of pregnancy but also looked at cardiovascular effects on the longer term [72, 74, 75]. A significant aortic root growth associated with pregnancy was observed in only one study (3 mm per pregnancy – interquartile range 0–7 mm). Aortic dissection was reported in a small subset of five women (Fig. 12.3). Type B aortic dissection was seen in four out of five cases. Although the latter observation warrants caution when advising patients to undergo elective surgery prior to pregnancy, large-scale studies are needed to confirm these findings. Also of note when interpreting these data is that in older cohorts (two out of these four studies [74, 75]), patients with other, more aggressive aortic disorders may have been included.

On the long-term adverse aortic outcome, defined as increased aortic root growth, the need for aortic surgery and aortic dissection was observed in two studies [72, 74]. Increased aortic root growth seemed more pronounced when the initial aortic root diameter equaled or exceeded 40 mm. Additionally, the study by Donnelly and colleagues showed increased adverse aortic outcome (defined as a composite of death, aortic dissection, the need for acute aortic surgery, and a severe symptomatic aortic regurgitation) in the parous versus nulliparous group. In multivariate analysis the initial aortic root diameter and the rate of aortic root growth during pregnancy were the principal predictors of long-term adverse outcome [72].

Some aspects in the interpretation of these data need consideration:


  1. 1.


    Some women included in these studies may actually have a genetically different diagnosis from MFS, as reflected by some unusual clinical features (carotid artery dissection is an uncommon feature in MFS, and type B aortic dissection occurs more frequently in other H-TAD entities).

     

  2. 2.


    The “comparison” group cannot be strictly considered a “control” group, because of occult biases in why those patients may have elected not to have any pregnancy.

     

Reports on pregnancy-related complications in MFS have obviously mainly focused on the aorta, but other notable risks include cardiac arrhythmias and venous thromboembolism (with respective OR of 10.64 and 5.25)and as reported in a retrospective analysis in 339 deliveries to women with MFS [77].

Overall, these studies indicate that in women known with a diagnosis of MFS and undergoing appropriate multidisciplinary care before, during, and after pregnancy, outcome of pregnancy on the short term is acceptable. Women contemplating pregnancy should be properly counseled about the associated risks before pregnancy.


12.2.4 Loeys–Dietz Syndrome


Loeys–Dietz syndrome (LDS) is caused by mutations in the genes encoding receptors for TGFβ (TGFBR1 and TGFBR2) and is clinically characterized by more generalized aortic aneurysms and involvement of branching vessels in association with some distinctive dysmorphic features (hypertelorism, bifid uvula) along with some systemic features that show overlap with MFS (pectus deformities, scoliosis)[25]. The first retrospective study of 21 pregnancies reported four aortic dissections and two uterine ruptures in patients with LDS. These women were not diagnosed with LDS prior to pregnancy and, hence, did not receive proper management [26]. A subsequent report by Attias and colleagues comparing patients with TGFBR2 mutations to patients with FBN1 mutations did not find significant differences between the two cohorts. Of the 39 pregnancies occurring among 17 women in the TGFBR2 cohort, one patient experienced sudden death in the immediate postpartum period (no diagnosis was made at that time). No aortic complications were reported during pregnancy or postpartum in the others. Among 87 women in the FBN1 cohort, 217 pregnancies occurred. Four of these patients presented with aortic dissection or death during pregnancy (p = 1) [78].

Prospective studies are currently ongoing, one of which is the data collection by the Montalcino Aortic Consortium (MAC) – data on 316 pregnancies in 122 women indicate that the risk for aortic dissection is low (five dissections reported) and mainly occurred in women who were unaware of the diagnosis and hence did not receive proper care at the time of their pregnancy. Women with more pronounced systemic features seem to be at an increased risk (G. Jondeau et al. 2016 unpublished data).


12.2.5 Aneurysm Osteoarthritis Syndrome


So far, no data on pregnancy-related complications in patients harboring mutations in the SMAD3 gene have been reported. In 1 retrospective series of 23 pregnancies in 13 women harboring a mutation in the SMAD3 gene, no vascular complications or uterine ruptures were reported. One patient suffered a postpartum hemorrhage [29]. As is the case with LDS, prospective data collection is ongoing and results are awaited.


12.2.6 Vascular Ehlers–Danlos Syndrome


Patients with vascular Ehlers–Danlos syndrome (vEDS) are characterized by extensive vascular fragility and may present arterial dissection without preceding dilatation. Management is challenging since imaging studies may not predict events. Results from a randomized trial with celiprolol showed a significant reduction in vascular events in the treated group [79]. vEDS is caused by mutations in the COL3A1 gene. Although the disease primarily affects major branching vessels of the aorta, the aorta itself may also be involved. In addition to these vascular complications, vEDS patients are also at risk for developing uterine rupture during pregnancy. Initial reports mentioned increased maternal mortality per pregnancy, ranging from 4.3 % to 25 % [21, 80, 81]. A more recent study, however, indicated that women with previous pregnancies did not have increased long-term mortality when compared to nulliparous women with vEDS [82]. The pregnancy-related death rate observed in this study covering 256 pregnancies in vEDS was 5.3 %. Based on these recent observations, counseling policies in women with vEDS have shifted from strongly discouraging pregnancy to a more nuanced vision with careful prepregnancy counseling of the couple addressing the risks as well as long-term prognosis in vEDS. In case of an affected child, there is an increased risk for premature rupture of the membranes due to their intrinsic fragility [83].


12.2.7 Other H-TADs


The outcome of pregnancy in women harboring mutations in the ACTA2 gene has been reported in one study [84]. Fifty-three women having a total of 137 pregnancies were included. Of these, eight had aortic dissections in the third trimester or the postpartum period (6 % of pregnancies). Notably, one woman also had a myocardial infarct during pregnancy that was independent of her aortic dissection, indicating that patients with ACTA2 mutations are also prone to cardiovascular disease outside the aorta. Assuming a population-based frequency of peripartum aortic dissections of 0.6 %, the rate of peripartum aortic dissections in women with ACTA2 mutations is significantly increased (8 out of 39; 20 %). Six of these reported dissections were Stanford type A dissections; three were fatal. Three women had ascending aortic dissections at diameters less that 5.0 cm (range 3.8–4.7 cm). Importantly, five out of the six women presenting with aortic dissection had hypertension, either during or before their pregnancy, indicating the importance of proper treatment.

In most of the other syndromic as well as in the vast majority of nonsyndromic H-TAD entities, very little or no data specifically related to pregnancy are available, and therefore, the recommendations are largely based on the knowledge obtained in MFS.


12.2.8 Turner Syndrome


Turner syndrome (TS) is a genetic sex chromosome disorder affecting approximately 1 in 2,000 live-born females, resulting from complete or partial absence of the X chromosome. The phenotype is highly variable and includes short stature, dysmorphic features, cardiovascular malformations, premature ovarian failure, and predisposition to autoimmune diseases. Different karyotype anomalies may lead to development of the syndrome, with or without cell line mosaicism, explaining part of the heterogeneity of clinical features. Monosomy X (45,X) has been associated with an increased risk of cardiac congenital anomalies [85].

Congenital cardiovascular anomalies can be divided into two main categories: aortic valve (mainly BAV) and thoracic vascular abnormalities (aortic coarctation and other arch anomalies) [85, 86].

With increasing age, the importance and impact of acquired cardiovascular disease on morbidity and mortality in Turner patients increase exponentially. A significant proportion will develop aortic dilation, ranging from 13 to 37 % in MRI studies, depending on the age group and measurement level along the aorta [85, 87]. Due to the short stature of Turner women, aortic diameters should be interpreted after correction for BSA. The BSA-normalized aortic diameter is termed aortic size index (ASI). An ASI above 20 mm/m2 is considered abnormal [88]. Excess cardiovascular mortality in TS is mainly due to ischemic heart disease, cerebrovascular disease, and aortic disease [85]. Aortic dissection is an important cause of early mortality, affecting Turner women mostly during the third and fourth decade of life (median age 35). The incidence is up to 100-fold increased compared to the general population, with a lifelong risk estimated at 1.4 % [88, 89]. Stanford type A aortic dissection is seen in about two-third of cases, compared to one-third of type B. Risk factors for aortic dissection in Turner patients are not well defined. The current acknowledged risk markers are mainly based on case reports and a registry-based surveys: aortic dilation, bicuspid aortic valve, aortic coarctation, karyotype 45,X, and hypertension [85, 90]. One prospective MRI-based study confirmed the predictive value of aortic dilation, with a high dissection rate in those with an ASI above 25 mm/m2 [88].

More recently, pregnancy has been recognized as a predisposing condition for aortic dissection in TS women, especially in the context of assisted reproductive technologies (ART) [91]. This aspect is important given the low rate of spontaneous pregnancy in TS women (2–7 %), mainly occurring in women with a mosaic karyotype [92, 93]. Most of the other pregnancies in TS are achieved through oocyte donation. Pregnancy-associated hypertensive disorders, including preeclampsia and gestational hypertension, are a major concern after oocyte donation in the general population (general incidence 16–40 %). This figure may rise up to 35–38 % in TS women [94, 95].

Since the late 1990s, several worrying case reports have been published on unexpected acute aortic dissection in pregnant TS women with a high maternal mortality rate (75 %) [94]. Aortic dissections occurred mainly during the third trimester and the early postpartum period, probably associated with the higher hemodynamic impact of pregnancy. Underlying congenital and acquired cardiovascular anomalies including BAV, coarctation of the aorta, or aortic dilation were present in the majority of published cases. However, aortic dissection may also occur in the absence of any of these. Half of the affected patients were known to have hypertension. Following these reports several national and international multicenter retrospective surveys were conducted in ART centers to determine the pregnancy outcome after oocyte donation in Turner patients, revealing an increased maternal mortality rate around 2 % related to acute aortic syndromes [9496]. Strikingly, less than half of Turner patients underwent cardiovascular screening before entering the OD program and only a quarter of them received echocardiographic follow-up during pregnancy.


12.3 Management


Management of women at risk for aortic complications during pregnancy requires a multidisciplinary approach at a tertiary center involving cardiologists, obstetricians, anesthesiologists, and medical geneticists.

Management of patients known to have aortic disease mainly consists of strict follow-up with aortic imaging, medical treatment aimed at reducing aortic wall stress, and prophylactic aortic surgery when indicated. Essentially, these strategies do not change in case of pregnancy, with the exception of the frequency of imaging and adjustment of the medical treatment in some cases.

Adequate and timely diagnosis of predisposing conditions, as well as prepregnancy counseling, and appropriate follow-up of patients at risk for an aortic event are essential to prevent fatal maternal and fetal outcome. In this section, we will discuss the different aspects of prevention of aortic dissection and rupture during pregnancy.

Strict and frequent follow-up of women with aortic aneurysms during pregnancy is the cornerstone of prevention of aortic dissection. Women with known aortopathy should be referred to a tertiary center for follow-up during pregnancy and management of delivery [97]. Regular echocardiographic follow-up should be scheduled every 4–8 weeks during pregnancy and up to 6 months’ postpartum. For those women with a dilated distal ascending aorta, aortic arch, or descending aorta, follow-up with MRI without gadolinium is recommended during pregnancy [55]. Careful blood pressure monitoring and treatment of hypertension is mandatory in all of these women.

Only gold members can continue reading. Log In or Register to continue

Aug 12, 2017 | Posted by in CARDIOLOGY | Comments Off on Aortopathy
Premium Wordpress Themes by UFO Themes