Stanford Type A Aortic Dissection in Pregnancy: A Diagnostic and Management Challenge

ORIGINAL ARTICLE

Original Article

Stanford Type A Aortic Dissection in Pregnancy: A Diagnostic and Management Challenge Stephanie L. Ch’ng, MBBS a,b,∗ , Andrew D. Cochrane, FRACS a,b , Jacob Goldstein, FRACS a,b and Julian A. Smith, FRACS a,b b

a Department of Cardiothoracic Surgery, Monash Medical Centre, Australia Department of Surgery (Monash Medical Centre), Monash University, Clayton, Victoria 3168, Australia

Background: In women under the age of 40, over 50% of type A aortic dissections occur in the obstetric population. This is a complex situation, with potential catastrophic outcomes for mother and child. Time to diagnosis is often delayed by a low degree of suspicion, atypical presentation and difficulties investigating pregnant women. Management requires early involvement of multiple teams and appreciation of potential complications. We report our experience (the largest series described) and describe our surgical strategy. Methods: A retrospective search of the cardiothoracic surgical database at our centre from 2002 to 2010 identified five pregnant women with type A dissections. Results: Median time to diagnosis was 18.5 h (range 5.5–150 h) and median time from diagnosis to arrival in the operating theatre was 1.5 h (range 0.5–54 h). Four patients underwent concomitant Caesarean section and dissection repair. There was one maternal death and one unrelated foetal death. Conclusion: Occurrence of type A aortic dissection in pregnant women is uncommon but potentially catastrophic. A high index of suspicion and timely investigations are necessary to expedite definitive management. Sound surgical strategies and collaboration with appropriate teams are necessary to optimise outcome. (Heart, Lung and Circulation 2013;22:12–18) © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved. Keywords. Ascending aorta; Dissection; Cardiovascular surgical procedures; Pregnancy; Diagnosis

Introduction

A

ortic dissection is an uncommon but lethal condition. Its occurrence during pregnancy can be devastating. In women under the age of 40, approximately 50% of aortic dissections occur during pregnancy [1]. Additionally, observational studies have attributed 3–10% of maternal mortality [2,3] to the concurrent presence of aortic dissection. This raises multiple complex issues for the clinician Received 26 January 2012; received in revised form 30 July 2012; accepted 6 August 2012; available online 16 October 2012 Abbreviations: BAV, bicuspid aortic valve; CT, computed tomography; CVA, cerebrovascular accident; GP, gravida/parity; IV, intravenous; MAP, mean arterial pressure; MFS, Marfan syndrome; MODS, multi-organ dysfunction syndrome; NVD, normal vaginal delivery; OT, operating theatre; PE, pulmonary embolus; POD, post-operative day; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; VQ scan, ventilation/perfusion scan. ∗ Corresponding author at: Monash Medical Centre, Department of Cardiothoracic Surgery, Clayton, Victoria 3169, Australia. Tel.: +61 4 1999 7880. E-mail addresses: [email protected] (S.L. Ch’ng), [email protected] (A.D. Cochrane), [email protected] (J. Goldstein), [email protected] (J.A. Smith).

from diagnosis to definitive management, with the primary goal being to save both mother and child. Since the first reported case of aortic dissection occurring in pregnancy [4], there have been over 80 cases documented in the literature. These are mainly case reports and small series, with the largest studies containing four patients with type A dissections [5,6]. The majority of cases reported occur in patients with known risk factors for aortic dissections, either known prior to presentation or diagnosed after the fact. Over 50% of reported cases of aortic dissection in pregnancy are associated with MFS [6,7], with the incidence of dissection in pregnancy in Marfan patients being 3% [8]. The risk is closely related to aortic diameter [8], with those at high risk having aortic diameters >40 mm or rapid dilatation of the aortic root or previous (non-pregnancy) dissection of the ascending aorta. Similarly, bicuspid aortic valve (BAV) aortopathy is also a known risk factor for type A dissections, occurring in 1–2% of the population [9] and responsible for 3–7% [10,11] of all aortic dissections. The histopathology, like that of MFS is cystic medial necrosis [12,13] and similarly, there are documented aortic diameter thresholds at which intervention is recommended: 5.0 cm or an increase of 0.5 cm/year [14].

© 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.

1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2012.08.005

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Ch’ng et al. Aortic Dissection in Pregnancy: A Challenge

Table 1. Patient Characteristics and Presentation. 1 Age (year month)

2

3

4

5

30 years 3 months

36 years 6 months

28 years 4 months

36 years 7 months

36 years 8 months

Ht

178 cm

177 cm

183 cm

143.5 cm

178 cm

Wt

90 kg

87 kg

86 kg

44.1 kg

105 kg

BSA

2.08 m2

2.02 m2

2.08 m2

1.32 m2

2.22 m2

Gravida/para

G1P0

G1P0

G3P1

G1P0

G1P0

Risk factors

MFS

Nil

MFS previous pre-eclampsia

Turner syndrome, BAV

BAV

Body habitus

Gestation (weeks)

37

32

37

21 (donor egg)

32

Presenting symptoms

Persistent cough, dyspnoea

Sudden severe sharp chest pain radiating to back

Left homonymous hemianopia, left hand weakness, dyspraxia

Hypertensive, epigastric pain

Right parasternal pleuritic chest pain

Provisional diagnosis

Aortic dissection

PE

Embolic CVA

Indigestion/preeclampsia

Acute pericarditis/PE

BAV, bicuspid aortic valve; MFS, Marfan syndrome; PE, Pulmonary embolus.

The average age was 33 years and 8 months (range from 28 years 4 months to 36 years 8 months), and the average gestation was 32 weeks. Four women were primigravid. Two women had known risk factors for aortic dissection on presentation (MFS and Turner Syndrome) and a further two women were diagnosed as having risk factors (MFS and BAV) during hospitalisation (Table 1). Presenting symptoms varied, ranging from epigastric pain to unilateral blindness. Working diagnoses were equally varied, with only one woman suspected of having an aortic dissection as an initial diagnosis (Table 1). Bedside transthoracic echocardiography (TTE) with confirmatory trans-oesophageal echocardiography (TOE) intra-operatively, was the main method of diagnosis. Only one patient had contrast computed tomography (CT) preoperatively. A TTE on this patient had initially been falsely negative. Median time from initial hospital presentation to diagnosis of aortic dissection was 18.5 h (range 5.5–150 h) and median time from diagnosis to arrival in the operating theatre was 1.5 h (range 0.5–54 h) (Table 2). Operative management was co-ordinated with a cardiac anaesthetist, obstetrician and neonatologist. The strategy for the women in late gestation was concomitant surgery with Caesarean section followed immediately by repair of the aortic dissection (Table 3). Foetal heart monitoring was continued from presentation to definitive management.

Turner syndrome is the commonest cause of aortic dissection in young women [15] and is associated with BAV in 30% of cases [16]. When patients with Turner aortopathy are subject to the vascular stresses of pregnancy, aortic dissection may precipitate. We expect this triad of factors to be encountered with increasing frequency as rates of pregnancy in this population rise, facilitated by assistedfertilisation and oocyte-donation. Other causes include Ehlers–Danlos syndrome and familial-dissection disorders. Eighty percent of aortic dissections occurring in pregnancy are type A dissections and 87.5% of these cases occur pre-partum [17].

Methods To ensure complete patient capture, we performed a retrospective review of three databases at Monash Medical Centre, Australia namely the Monash Medical Centre Cardiothoracic Surgery database, the Australasian Society of Cardiac and Thoracic Surgeons database and the Monash Medical Centre Medical records. Between 2002 and 2010, 223 patients (150 men and 74 women) were admitted to Monash Medical Centre with acute aortic dissection. Of the dissections occurring in women, five occurred in patients diagnosed with both type A dissection and pregnancy. Table 2. Patient Investigations. 1 Initial Ix

TTE

2

3

4

5

VQ scan

TTE (positive for aortic dissection)

TTE

VQ scan

Definitive Ix

TTE

TTE

CT chest contrast

TTE

TTE

Time from ED presentation to diagnosis

15.5 h

5.5 h

150.5 h

18.5 h

20.5 h

Time from diagnosis to arrival in OT

1.5 h

1.5 h

54 h

0.5 h

2h

CT chest contrast, computed tomography of the chest with IV contrast; h, hours; OT, operating theatre; TTE, transthoracic echocardiogram; VQ scan, ventilation/perfusion scan.

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Ch’ng et al. Aortic Dissection in Pregnancy: A Challenge

Heart, Lung and Circulation 2013;22:12–18

Table 3. Foetal Strategy and Outcome. 1

2

3

4

5

Gestation (weeks)

37

32

37

21

32

Delivery

Concomitant Caesarean and aortic repair

Concomitant Caesarean and aortic repair

Urgent Caesarean delivery due to possible need for anticoagulation

Aborted

Concomitant Caesarean and aortic repair

Apgar scores (1 min, 5 min)

5, 8

6, 7

8, 9

N/A

2, 5

Need for endotracheal intubation

No

Yes

No

N/A

Yes

Outcome

Survived

Survived

Survived

Deceased

Survived

We describe here our operative strategy (Table 4). Sternotomy was performed first, to enable urgent cardiopulmonary bypass if haemodynamic instability developed during the Caesarean section. Depending on the patient’s haemodynamic status, the axillary or femoral artery and vein were dissected out. At the same time, Caesarean section was performed by the obstetrician. To minimise intra-abdominal bleeding during the cardiac portion of the operation, syntocinon was used (topically or intravenously at low dose) and the abdomen packed and left open during the aortic repair. A neonatologist was present to receive the baby. Emergency delivery of viable but immature foetuses may result in the need for endotracheal intubation, as seen in two of our babies delivered at 32 weeks gestation. These premature babies also required admission to the neonatal intensive care unit. The appropriate repair of the dissection was then carried out. Decisions regarding femoral or axillary cannulation, use of deep-hypothermic circulatory-arrest, antegrade vs. retrograde cerebral perfusion were determined individually, according to the surgeon, pathology, foetal-age and current surgical techniques. The abdomen was then re-examined and closed. An attempt to continue the pregnancy for patient 4 was made as the foetus was deemed not viable at 21 weeks

gestation and therefore deep-hypothermic circulatoryarrest was not used. However at the conclusion of the cardiac surgery, the patient was found to be in renal failure and after consultation with the obstetrician, a diagnosis of pre-eclamptic anuric renal-failure was made and the pregnancy was terminated.

Results Histopathology of the aortic specimens demonstrated mild to severe myxoid degeneration of the media (Table 5). The median time in the intensive care unit was two days (range one to nine days). Two patients required a return to the operating theatre. Patient 2 had a planned return for washout of the sternal wound, initially left open due to severe coagulopathy, while patient 4 had an emergency return for bleeding. Two patients developed transient renal impairment not requiring haemofiltration or dialysis (Table 5). There was one maternal death from multi-organ failure and one foetal death as described above. All surviving mothers were advised against further pregnancy. Patients 1 and 3 were reviewed by a clinical geneticist confirming the diagnosis of Marfan syndrome. Patient 5 was referred for further genetic review but did not attend. All surviving patients undergo regular investigation and review to monitor for progression of disease.

Table 4. Operative Strategies. 1

2

3

4

5

Anaesthesia

General

General

General

General

General

Operation

Aortic root replacement

Ascending aortic replacement with resuspension of the aortic valve

Ascending aortic and hemi-arch replacement

Supracommissural replacement of the ascending aorta

Aortic root replacement

Bypass/Xclamp time (min)

155/122

286/85

186/116

134/101

182/109

Circulatory arrest (min)

0

30

49

0

19

Cerebral perfusion

Antegrade

Antegrade

Antegrade

Antegrade

Retrograde

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Table 5. Histopathology and Complications. 1

2

3

4

5

Histopathology

Severe myxoid degeneration

Mild myxoid degeneration

Myxoid degeneration

Mild myxoid degeneration

Myxoid degeneration

Complications

Acute renal impairment

MODS return to theatre (planned)

Nil

Return to theatre for – bleeding prolonged ICU stay

Nil

Outcome

Survived

Deceased

Survived

Survived

Survived

Follow up

Genetic clinic; confirmed MFS

Genetic clinic confirmed MFS

MFS, Marfan syndrome; MODS, multi-organ dysfunction syndrome.

Discussion The causal relationship between pregnancy and aortic dissection is disputed by some authors [18,19]. However it is generally accepted that pregnancy is a precipitating factor in patients who are already susceptible to developing aortic dissection. During pregnancy, both haemodynamic and structural changes occur in the aortic wall. The haemodynamic stresses peak at 32 weeks gestation because of a 50% increase in intravascular volume [20]. Furthermore, stroke volume and heart rate also increase, resulting in an increased cardiac output of 40–50% [21]. Histological studies of the human maternal aorta have shown changes, most pronounced in late gestation [22], which include disruption of elastic lamellae, decreased ground-substance and hypertrophy and hyperplasia of vascular smooth muscle cells. Hormones oestrogen and relaxin, which peak in late gestation, have been implicated [23]. Oestrogen enhances the release of matrixmetalloproteinase 2, which has been found to alter lumen diameter and compliance. Relaxin, which ripens the cervix and softens the pubic symphysis in preparation for labour, enhances matrix-metalloproteinase 3 mRNA in oestrogen-primed cells. This enzyme is responsible for digesting various proteins essential in maintaining the structural integrity of the vascular wall [24]. This combination of vascular stress and change of aortic tunica media architecture in an already abnormal aorta predisposes to dissection. Consistent with the literature, 80% of our cases occurred during the third trimester.

Risk Factors Only one of the women, patient 4, had a known risk factor (Turner syndrome) for aortic dissection at the time of admission. However she had not had pre-pregnancy screening echocardiography. A further three women in our series were found to have risk factors for aortic dissection (Table 1) during the admission or subsequently. Patient 1 and 3 were diagnosed with Marfan syndrome and patient 5, with bicuspid aortic valve.

Presentation and Investigations Diagnosing type A dissection can be challenging, particularly during pregnancy. It can masquerade as a

number of entities including acute myocardial infarction, pre-eclampsia, pulmonary embolism and acute pancreatitis [25], depending on which of the aortic branches are compromised. In the obstetric population, the incidence of pulmonary embolism (3–40/1000 [26]) and pre-eclampsia (50/1000 [27]) far exceeds that of aortic dissection (0.0145/1000 [28]). Aortic dissection is therefore often overlooked. As recommended by the European Society of Cardiology (ESC) guidelines for the management of cardiovascular diseases during pregnancy, any pregnant woman presenting with acute chest pain must be considered for aortic dissection, alongside myocardial infarction, pre-eclampsia and pulmonary embolism [29]. In the case series described, three patients underwent V/Q scans prior to investigations for aortic dissection. With mortality increasing by 1–2% hourly for the first 48 h, time from presentation to diagnosis is critical. The recommendation to continue investigations if the initial study reveals ‘no definitive findings’ and suspicion of aortic dissection remains [30] is pertinent to patient 3. Her initial TTE was reported as negative for aortic dissection. This resulted in a delay to diagnosis, which was eventually made six days after admission. Chest roentography is often normal or non-specific [31]. Occasionally it may demonstrate a widened mediastinum. It is often omitted because of concerns regarding foetal radiation. The previous “gold standard” of invasive aortography has been largely superseded by newer technologies such as CT and echocardiography. New generation CT scanners have almost 100% sensitivity and 98–99% specificity for the diagnosis of aortic dissection [32,33]. Furthermore, they are quick, almost universally available, detect subtle changes between acute aortic diseases such as aortic ulceration or intramural haematoma and demonstrate anatomical detail highly valuable in surgical preparation. Furthermore, CT scans do not require the presence of a radiologist or other personnel required for invasive aortography. Although there are risks associated with radiation to the foetus, we believe this is outweighed by the risk of an undiagnosed dissection in a patient in whom a dissection is suspected. Echocardiography has minimal side-effects and can provide functional assessments of the heart. The quality of TTE however is variable, and affected by both proceduralist skill and chest-wall morphology [34]. It has documented

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Ch’ng et al. Aortic Dissection in Pregnancy: A Challenge

sensitivities of 59–83% and specificities of 63–93% [35]. Therefore a negative result may be incorrect and further investigation is warranted if suspicion of aortic dissection remains. It is a practical tool for initial assessment but accessibility and time taken to organise is facilitydependent. In the hands of an experienced technician, TOE has sensitivities and specificities equivalent to CT [34] and is the recommended diagnostic tool for unstable patients with suspected aortic dissection. It can be performed by the bedside or on the operating table and can provide anatomical and functional information for the surgeon. Its limitations are the availability of an experienced echocardiographer, the need to sedate the patient and poor visualisation of the aortic arch and its vessels. Magnetic resonance imaging [MRI] is increasing in popularity as its accessibility improves. It has sensitivities and specificities equivalent to or exceeding that of CT and TEE [34]. MRI can provide information concerning branch artery involvement, aortic valve pathology and left ventricular dysfunction without exposing the patient to ionised-radiation [33]. However MRI safety in pregnancy and its potential side effects to the foetus is not wellestablished. The long time required in the supine position with aortocaval-compression and isolation from immediate medical care are definite concerns. Although available in our centre, MRI was not used to diagnose aortic dissection in our patients. The impact of the low degree of suspicion and investigative challenges can be seen in the delayed time to diagnosis, 18.5 h in our series compared with 4.3 h for all patients, reported by the International Registry of Acute Aortic Dissection [36].

Surgery Aortic dissection surgery in the obstetric population is complex. Communication and planning between multiple teams is essential. Medical personnel involved in operative planning at our centre include the perfusionist, cardiac anaesthetist, cardiologist, obstetrician, neonatologist and cardiac surgeon. The gestations at which it is appropriate to deliver the foetus is unclear. Cardiac surgeons involved in the repair of an acute aortic dissection in pregnancy are typically not at liberty to delay surgery to optimise foetal outcome. We would suggest reassessment of recommendations by Immer that “repair should be carried out without delivery. . .at gestation <30 weeks and for gestation >30 weeks, concomitant surgery with Caesarean section followed immediately by repair” [17]. With ongoing improvements in neonatal care, pre-term infant survival is improving. The Australian New Zealand Neonatal Network reported 94% survival at 28 weeks gestation and 98% survival at 30 weeks gestation [37]. The difference is small and the potential risks of maternal cardiopulmonary bypass on the foetus are large. Therefore we suggest that there is potential to lower the recommendation to 28 weeks gestation. Discussion between the neonatologist,

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obstetrician and cardiac surgeon is essential in each case. For the patient undergoing repair with the undelivered foetus, there are well-described recommendations in the literature. These include intra-operative foetal-heart monitoring [38,39], avoidance of deep hypothermic circulatory arrest [40,41] and maintaining a mean arterial pressure greater than 70 mmHg [42].

Follow up Long term monitoring with excellent blood pressure control and regular imaging is mandatory in order to detect ongoing dilation of the residual aorta [in which case consideration needs to be given to either intravascular stenting or reoperation] and to assess aortic valve function [34]. Genetic testing is reasonable for those without known risk factors for aortic dissection. Counselling regarding further pregnancies, employment and lifestyle restrictions should also be given. The patient should be made aware that her immediate family including the baby may also have an increased risk of aortic dissection.

Limitations Although efforts were made to ensure no patients were omitted from the study, it is possible that some pregnant patients with type A dissections may have died without diagnosis.

Conclusion To our knowledge, this is the largest reported single-centre case series describing type A dissection occurring in pregnancy in the literature. A high degree of suspicion, rapid action to both diagnose and provide definitive management and a team approach are central to a good outcome. It is important that any pregnant woman presenting with acute chest pain be considered to have myocardial infarction, a pulmonary embolus or an aortic dissection until proven otherwise.

Conflicts of Interest Nil for all authors.

Acknowledgements Study conception and design were done by Goldstein, Cochrane, Ch’ng. Data acquisition were carried out by Goldstein and Ch’ng. Data analysis and interpretation were done by Ch’ng, Goldstein, Cochrane and Smith. Drafting of manuscript was done by Ch’ng. Critical revision by Cochrane, Smith, Goldstein. Ch’ng is guarantor.

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