- Email: [email protected]
Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient
Accepted Manuscript Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient Joyce Ji, MD, J. Trevor Posenau, MD, Kathryn J. Lindley, MD, Alan C. Braverman, MD PII:
S0002-9343(15)01022-0
DOI:
10.1016/j.amjmed.2015.09.023
Reference:
AJM 13231
To appear in:
The American Journal of Medicine
Received Date: 15 September 2015 Accepted Date: 16 September 2015
Please cite this article as: Ji J, Posenau JT, Lindley KJ, Braverman AC, Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.09.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient Joyce Ji, MD1, J. Trevor Posenau, MD1,2, Kathryn J. Lindley, MD1,2, Alan C. Braverman, MD1,2 Department of Internal Medicine, 2Cardiovascular Division, Washington University School of Medicine, St. Louis, MO
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1
Article type: Diagnostic Dilemma
Key words: pregnancy; aortic dissection; hypertension; aortopathy
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Funding: None. Conflict of interest: None.
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Authorship: All authors had access to the data and were involved in the conception and drafting of this article.
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EP
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Address correspondence to: Joyce Ji, MD, Department of Internal Medicine, Washington University School of Medicine, 4901 Forest Park Ave., Suite 241, St. Louis, MO 63108. Email address: [email protected].
ACCEPTED MANUSCRIPT
Presentation A 27-year-old G4P1021 African American woman presented at 9 weeks gestation with elevated blood pressure. The patient was otherwise asymptomatic, denying
RI PT
headache, vision changes, chest pain, shortness of breath, or neurologic symptoms. Her previous pregnancies were uncomplicated, with no history of hypertensive disorders of
pregnancy. She had a two-year history of chronic hypertension, but had self-discontinued
SC
medications prior to presentation. She had no other chronic medical conditions. Family
M AN U
history was significant only for hypertension in both parents.
Assessment
Initial blood pressure was 192/115, with a heart rate of 95 and respiratory rate of
TE D
18. Height was 5 foot 8 inches. She had a normal uvula and palate, no hypertelorism, and normal sclera. She did not have excessively velvety or soft skin, no elongated fingers or toes, and no pectus deformity. Cardiac examination revealed a short systolic ejection
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murmur with no diastolic murmur, and the pulse exam was normal. She had no features of a syndromic connective tissue disorder. Electrocardiogram revealed normal sinus
AC C
rhythm with nonspecific T-wave abnormalities. Initial laboratory evaluation revealed electrolytes and creatinine to be within
normal limits. Aldosterone:renin ratio was normal. Renal ultrasound showed no evidence of renal artery stenosis. Transthoracic echocardiogram showed normal left ventricular systolic function with mild concentric left ventricular hypertrophy and a trileaflet aortic valve. Suprasternal notch views were suggestive of coarctation of the aorta with
ACCEPTED MANUSCRIPT
continuous wave Doppler peak velocity of ~2.5 m/s and peak pressure gradient of 25 mmHg in the proximal descending aorta, along with a narrow turbulent jet across this area (Figure 1). Subsequent magnetic resonance angiogram and follow-up contrast CT of
RI PT
the aorta did not show evidence of aortic coarctation, but instead demonstrated a type B aortic dissection extending from just distal to the left subclavian artery to below the renal arteries, with aneurysmal enlargement of the proximal descending aorta measuring 5.0 x
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renal artery arising from the false lumen.
SC
5.8 cm (Figure 2). Fenestrations were present in the intimal flap, with the celiac and left
Diagnosis
The patient’s history and imaging were most consistent with chronic type B aortic dissection. On further questioning, the patient reported an episode of acute tearing chest
TE D
and back pain that occurred during an argument two years prior to presentation. The pain was self-limited and was not evaluated at that time. Aortic dissection in pregnancy is a rare but potentially life-threatening disease. In
EP
women of childbearing age, approximately 12-50% of aortic dissections occur in the setting of pregnancy or the post-partum state, representing up to a 25-fold increase in the
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risk of dissection1-5. The physiologic changes of pregnancy may increase risk for aortic dissection due to an increased hemodynamic load and hormonal-induced changes in aortic wall histology. During pregnancy, cardiac output is increased by up to 50%, due to increase in plasma volume and heart rate, thus increasing hemodynamic stress on the walls of the aorta6,7. Elevated estrogen levels during pregnancy may also remodel the vascular media, suppressing the synthesis of collagen and elastin7,8. Aortic dissection is
ACCEPTED MANUSCRIPT
an established pregnancy-related risk for women with inherited or congenital aortopathies such as Marfan syndrome, Loeys-Dietz syndrome, familial thoracic aortic aneurysm, coarctation of the aorta, and bicuspid aortic valve-associated aortopathy9-11. The
RI PT
underlying aortopathies that predispose patients to aortic dissections are often related to mutations in genes associated with familial thoracic aortic aneurysms including FBN1,
TGFBR1, TGFBR2, ACTA2, COL3A1, MYH11, and others12,13. However, this patient did
SC
not have clear evidence of a heritable or syndromic aortopathy by history, physical exam, or imaging. It was recommended that our patient undergo genetic testing, but she
M AN U
declined due to the expense. It has also been recommended that her first-degree family members be screened for thoracic aortic aneurysm.
Management
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There are limited data to guide the management of chronic type B aortic dissections in pregnancy. Strict blood pressure and heart rate control is imperative when managing aortic dissections12,14. Beta-blockers reduce shear stress on vessel walls and
EP
slow the rate of aortic dilation6,7. Our patient was initially started on labetalol for heart
AC C
rate and blood pressure control, with nifedipine and hydralazine added to achieve a goal systolic blood pressure under 120 mmHg. There are no guidelines addressing the safety of pregnancy with chronic aortic
dissection. According to the World Health Organization pregnancy guidelines, pregnancy is generally contraindicated for women with aortic diameter exceeding 4.5 cm in patients with Marfan syndrome or other syndromes with high risk of dissection14,15. Although this patient did not have an identified inherited aortopathy, her dissected and aneurysmal
ACCEPTED MANUSCRIPT
descending thoracic aorta measuring 5.8 cm was felt to put her at significantly increased risk of progressive aortic dilatation and aortic rupture with the hemodynamic stress of pregnancy6-8.
RI PT
Given our patient’s high risk for maternal and fetal complications, the
multidisciplinary cardiovascular and obstetrics teams advised termination of the
pregnancy. Therapeutic abortion via suction dilation and curettage was performed, along
SC
with placement of a subdermal contraceptive implant for provision of long acting
reversible contraception16. The patient was discharged on an anti-hypertensive regimen of
M AN U
labetalol, nifedipine, hydrochlorothiazide, and lisinopril. Two months later, she underwent thoracic endovascular repair with a 32x160 mm Zenith® TX2® endovascular graft covering a portion of the left carotid origin and the entire left subclavian origin. She also required left carotid ostial stenting and left carotid-subclavian bypass using an 8-mm
TE D
Propaten® graft.
On follow-up, the patient’s blood pressure has been well-controlled. Subsequent diagnostic angiogram revealed retrograde flow through the left subclavian artery, and
EP
embolization of the proximal left subclavian artery was then performed. Most recent CT has demonstrated stable aortic diameter and decreased false lumen size (Figure 3).
AC C
Our patient’s unique presentation posed a diagnostic and therapeutic challenge.
Chronic aortic dissection discovered during pregnancy is highly uncommon and should trigger an evaluation for an underlying hereditary thoracic aortic aneurysm syndrome, including a thorough clinical examination and mutation analysis. Furthermore, careful consideration of the potential repercussions for the mother and the fetus is crucial.
ACCEPTED MANUSCRIPT
1. Nasiell J, Lindqvist PG. Aortic dissection in pregnancy: the incidence of a lifethreatening disease. Eur J Obstet Gynecol Reprod Biol 2010;149:120-121. 2. Schnitker MA, Bayer CA. Dissecting aneurysm of the aorta in young individuals,
1944;20:486-511.
RI PT
particularly in association with pregnancy: with a report of a case. Ann Intern Med
pregnancy. N Engl J Med 1954;251:1059-1061.
SC
3. Mandel W, Evans EW, Walford RL. Dissecting aortic aneurysm during
4. Hirst AE, Johns VJ, Kime SW. Dissecting aneurysm of the aorta. A review of 505
M AN U
cases. Medicine 1958;37:217-279.
5. Braverman AC, Harris K, Pyeritz R, et al. Aortic dissection During Pregnancy: Results From the International Registry of Acute Aortic Dissection (IRAD). J Am Coll Cardiol 2012;59:A467.
TE D
6. Van Hagen IM, Roos-Hesselink JW. Aorta pathology and pregnancy. Best Pract Res Clin Obstet Gynaecol 2014;28(4):537-550. 7. Smok, DA. Aortopathy in pregnancy. Seminars in Perinatology 2014;38:295-303.
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8. Westhoff-Bleck M, Podewski E, Hilfker A, et al. Cardiovascular disorders in pregnancy: diagnosis and management. Best Pract Res Clin Obstet Gynaecol
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2013;27:821-834.
9. Rajagopalan S, Nwazota N, Chandrasekhar S. Outcomes in pregnant women with acute aortic dissections: a review of literature from 2003 to 2013. Int J Obstet Anesth 2014;23:348-356.
10. Braverman AC. Acute aortic dissection: clinician update. Circulation 2010;122:184-188.
ACCEPTED MANUSCRIPT
11. Gleason TG. Heritable disorders predisposing to aortic dissection. Semin Thorac Cardiovasc Surg 2005;17:274-281. 12. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010
RI PT
ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the
diagnosis and management of patients with Thoracic Aortic Disease. Circulation 2010;121:e266–e369.
SC
13. Gillis E, Van Laer L, Loeys BL. Genetics of thoracic aortic aneurysm: at the
M AN U
crossroad of transforming growth factor-β signaling and vascular smooth muscle cell contractility. Circ Res 2013;113:327-340.
14. Regitz-Zagrosek V, Lundqvist CB, Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European
TE D
Society of Cardiology (ESC). Eur Heart J 2011;32:3147-3197. 15. Balci A, Sollie-Szarynska K, van der Bijl A, et al. Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with
EP
congenital heart disease. Heart 2014;100:1373-1381.
AC C
16. Thorne S, MacGregor A, Nelson-Piercy C. Risks of contraception and pregnancy in heart disease. Heart 2006;92:1520-1525.
ACCEPTED MANUSCRIPT
Figure 1. Transthoracic echocardiogram demonstrating A) dilated descending aorta. B) Color flow Doppler demonstrating a turbulent jet in proximal descending aorta. C)
gradient (25 mmHg) across the “narrowing.”
RI PT
Continuous wave Doppler demonstrating increased velocity (~2.5 m/s) and peak pressure
Figure 2. Contrast CT demonstrating a type B aortic dissection with an intimal flap
SC
(black arrow) and a 5.8 cm thoracic aortic aneurysm. A) Sagittal view. B) Axial view.
M AN U
Figure 3. CT angiogram 7 months after thoracic endovascular aortic repair. A) Sagittal view demonstrating stent graft in place as well as stent in the left common carotid artery and AmplatzerTM (St. Jude Medical, Inc) plugs in the left subclavian artery. B) Axial view demonstrating progressive thrombosis of the false lumen (white arrow) and decreased
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EP
TE D
aneurysm size.
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EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
TE D
M AN U
SC
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ACCEPTED MANUSCRIPT
S0002-9343(15)01022-0
DOI:
10.1016/j.amjmed.2015.09.023
Reference:
AJM 13231
To appear in:
The American Journal of Medicine
Received Date: 15 September 2015 Accepted Date: 16 September 2015
Please cite this article as: Ji J, Posenau JT, Lindley KJ, Braverman AC, Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient, The American Journal of Medicine (2015), doi: 10.1016/j.amjmed.2015.09.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Dissecting the Dilemma: Uncontrolled Hypertension in a Pregnant Patient Joyce Ji, MD1, J. Trevor Posenau, MD1,2, Kathryn J. Lindley, MD1,2, Alan C. Braverman, MD1,2 Department of Internal Medicine, 2Cardiovascular Division, Washington University School of Medicine, St. Louis, MO
RI PT
1
Article type: Diagnostic Dilemma
Key words: pregnancy; aortic dissection; hypertension; aortopathy
SC
Funding: None. Conflict of interest: None.
M AN U
Authorship: All authors had access to the data and were involved in the conception and drafting of this article.
AC C
EP
TE D
Address correspondence to: Joyce Ji, MD, Department of Internal Medicine, Washington University School of Medicine, 4901 Forest Park Ave., Suite 241, St. Louis, MO 63108. Email address: [email protected].
ACCEPTED MANUSCRIPT
Presentation A 27-year-old G4P1021 African American woman presented at 9 weeks gestation with elevated blood pressure. The patient was otherwise asymptomatic, denying
RI PT
headache, vision changes, chest pain, shortness of breath, or neurologic symptoms. Her previous pregnancies were uncomplicated, with no history of hypertensive disorders of
pregnancy. She had a two-year history of chronic hypertension, but had self-discontinued
SC
medications prior to presentation. She had no other chronic medical conditions. Family
M AN U
history was significant only for hypertension in both parents.
Assessment
Initial blood pressure was 192/115, with a heart rate of 95 and respiratory rate of
TE D
18. Height was 5 foot 8 inches. She had a normal uvula and palate, no hypertelorism, and normal sclera. She did not have excessively velvety or soft skin, no elongated fingers or toes, and no pectus deformity. Cardiac examination revealed a short systolic ejection
EP
murmur with no diastolic murmur, and the pulse exam was normal. She had no features of a syndromic connective tissue disorder. Electrocardiogram revealed normal sinus
AC C
rhythm with nonspecific T-wave abnormalities. Initial laboratory evaluation revealed electrolytes and creatinine to be within
normal limits. Aldosterone:renin ratio was normal. Renal ultrasound showed no evidence of renal artery stenosis. Transthoracic echocardiogram showed normal left ventricular systolic function with mild concentric left ventricular hypertrophy and a trileaflet aortic valve. Suprasternal notch views were suggestive of coarctation of the aorta with
ACCEPTED MANUSCRIPT
continuous wave Doppler peak velocity of ~2.5 m/s and peak pressure gradient of 25 mmHg in the proximal descending aorta, along with a narrow turbulent jet across this area (Figure 1). Subsequent magnetic resonance angiogram and follow-up contrast CT of
RI PT
the aorta did not show evidence of aortic coarctation, but instead demonstrated a type B aortic dissection extending from just distal to the left subclavian artery to below the renal arteries, with aneurysmal enlargement of the proximal descending aorta measuring 5.0 x
M AN U
renal artery arising from the false lumen.
SC
5.8 cm (Figure 2). Fenestrations were present in the intimal flap, with the celiac and left
Diagnosis
The patient’s history and imaging were most consistent with chronic type B aortic dissection. On further questioning, the patient reported an episode of acute tearing chest
TE D
and back pain that occurred during an argument two years prior to presentation. The pain was self-limited and was not evaluated at that time. Aortic dissection in pregnancy is a rare but potentially life-threatening disease. In
EP
women of childbearing age, approximately 12-50% of aortic dissections occur in the setting of pregnancy or the post-partum state, representing up to a 25-fold increase in the
AC C
risk of dissection1-5. The physiologic changes of pregnancy may increase risk for aortic dissection due to an increased hemodynamic load and hormonal-induced changes in aortic wall histology. During pregnancy, cardiac output is increased by up to 50%, due to increase in plasma volume and heart rate, thus increasing hemodynamic stress on the walls of the aorta6,7. Elevated estrogen levels during pregnancy may also remodel the vascular media, suppressing the synthesis of collagen and elastin7,8. Aortic dissection is
ACCEPTED MANUSCRIPT
an established pregnancy-related risk for women with inherited or congenital aortopathies such as Marfan syndrome, Loeys-Dietz syndrome, familial thoracic aortic aneurysm, coarctation of the aorta, and bicuspid aortic valve-associated aortopathy9-11. The
RI PT
underlying aortopathies that predispose patients to aortic dissections are often related to mutations in genes associated with familial thoracic aortic aneurysms including FBN1,
TGFBR1, TGFBR2, ACTA2, COL3A1, MYH11, and others12,13. However, this patient did
SC
not have clear evidence of a heritable or syndromic aortopathy by history, physical exam, or imaging. It was recommended that our patient undergo genetic testing, but she
M AN U
declined due to the expense. It has also been recommended that her first-degree family members be screened for thoracic aortic aneurysm.
Management
TE D
There are limited data to guide the management of chronic type B aortic dissections in pregnancy. Strict blood pressure and heart rate control is imperative when managing aortic dissections12,14. Beta-blockers reduce shear stress on vessel walls and
EP
slow the rate of aortic dilation6,7. Our patient was initially started on labetalol for heart
AC C
rate and blood pressure control, with nifedipine and hydralazine added to achieve a goal systolic blood pressure under 120 mmHg. There are no guidelines addressing the safety of pregnancy with chronic aortic
dissection. According to the World Health Organization pregnancy guidelines, pregnancy is generally contraindicated for women with aortic diameter exceeding 4.5 cm in patients with Marfan syndrome or other syndromes with high risk of dissection14,15. Although this patient did not have an identified inherited aortopathy, her dissected and aneurysmal
ACCEPTED MANUSCRIPT
descending thoracic aorta measuring 5.8 cm was felt to put her at significantly increased risk of progressive aortic dilatation and aortic rupture with the hemodynamic stress of pregnancy6-8.
RI PT
Given our patient’s high risk for maternal and fetal complications, the
multidisciplinary cardiovascular and obstetrics teams advised termination of the
pregnancy. Therapeutic abortion via suction dilation and curettage was performed, along
SC
with placement of a subdermal contraceptive implant for provision of long acting
reversible contraception16. The patient was discharged on an anti-hypertensive regimen of
M AN U
labetalol, nifedipine, hydrochlorothiazide, and lisinopril. Two months later, she underwent thoracic endovascular repair with a 32x160 mm Zenith® TX2® endovascular graft covering a portion of the left carotid origin and the entire left subclavian origin. She also required left carotid ostial stenting and left carotid-subclavian bypass using an 8-mm
TE D
Propaten® graft.
On follow-up, the patient’s blood pressure has been well-controlled. Subsequent diagnostic angiogram revealed retrograde flow through the left subclavian artery, and
EP
embolization of the proximal left subclavian artery was then performed. Most recent CT has demonstrated stable aortic diameter and decreased false lumen size (Figure 3).
AC C
Our patient’s unique presentation posed a diagnostic and therapeutic challenge.
Chronic aortic dissection discovered during pregnancy is highly uncommon and should trigger an evaluation for an underlying hereditary thoracic aortic aneurysm syndrome, including a thorough clinical examination and mutation analysis. Furthermore, careful consideration of the potential repercussions for the mother and the fetus is crucial.
ACCEPTED MANUSCRIPT
1. Nasiell J, Lindqvist PG. Aortic dissection in pregnancy: the incidence of a lifethreatening disease. Eur J Obstet Gynecol Reprod Biol 2010;149:120-121. 2. Schnitker MA, Bayer CA. Dissecting aneurysm of the aorta in young individuals,
1944;20:486-511.
RI PT
particularly in association with pregnancy: with a report of a case. Ann Intern Med
pregnancy. N Engl J Med 1954;251:1059-1061.
SC
3. Mandel W, Evans EW, Walford RL. Dissecting aortic aneurysm during
4. Hirst AE, Johns VJ, Kime SW. Dissecting aneurysm of the aorta. A review of 505
M AN U
cases. Medicine 1958;37:217-279.
5. Braverman AC, Harris K, Pyeritz R, et al. Aortic dissection During Pregnancy: Results From the International Registry of Acute Aortic Dissection (IRAD). J Am Coll Cardiol 2012;59:A467.
TE D
6. Van Hagen IM, Roos-Hesselink JW. Aorta pathology and pregnancy. Best Pract Res Clin Obstet Gynaecol 2014;28(4):537-550. 7. Smok, DA. Aortopathy in pregnancy. Seminars in Perinatology 2014;38:295-303.
EP
8. Westhoff-Bleck M, Podewski E, Hilfker A, et al. Cardiovascular disorders in pregnancy: diagnosis and management. Best Pract Res Clin Obstet Gynaecol
AC C
2013;27:821-834.
9. Rajagopalan S, Nwazota N, Chandrasekhar S. Outcomes in pregnant women with acute aortic dissections: a review of literature from 2003 to 2013. Int J Obstet Anesth 2014;23:348-356.
10. Braverman AC. Acute aortic dissection: clinician update. Circulation 2010;122:184-188.
ACCEPTED MANUSCRIPT
11. Gleason TG. Heritable disorders predisposing to aortic dissection. Semin Thorac Cardiovasc Surg 2005;17:274-281. 12. Hiratzka LF, Bakris GL, Beckman JA, et al. 2010
RI PT
ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the
diagnosis and management of patients with Thoracic Aortic Disease. Circulation 2010;121:e266–e369.
SC
13. Gillis E, Van Laer L, Loeys BL. Genetics of thoracic aortic aneurysm: at the
M AN U
crossroad of transforming growth factor-β signaling and vascular smooth muscle cell contractility. Circ Res 2013;113:327-340.
14. Regitz-Zagrosek V, Lundqvist CB, Borghi C, et al. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European
TE D
Society of Cardiology (ESC). Eur Heart J 2011;32:3147-3197. 15. Balci A, Sollie-Szarynska K, van der Bijl A, et al. Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with
EP
congenital heart disease. Heart 2014;100:1373-1381.
AC C
16. Thorne S, MacGregor A, Nelson-Piercy C. Risks of contraception and pregnancy in heart disease. Heart 2006;92:1520-1525.
ACCEPTED MANUSCRIPT
Figure 1. Transthoracic echocardiogram demonstrating A) dilated descending aorta. B) Color flow Doppler demonstrating a turbulent jet in proximal descending aorta. C)
gradient (25 mmHg) across the “narrowing.”
RI PT
Continuous wave Doppler demonstrating increased velocity (~2.5 m/s) and peak pressure
Figure 2. Contrast CT demonstrating a type B aortic dissection with an intimal flap
SC
(black arrow) and a 5.8 cm thoracic aortic aneurysm. A) Sagittal view. B) Axial view.
M AN U
Figure 3. CT angiogram 7 months after thoracic endovascular aortic repair. A) Sagittal view demonstrating stent graft in place as well as stent in the left common carotid artery and AmplatzerTM (St. Jude Medical, Inc) plugs in the left subclavian artery. B) Axial view demonstrating progressive thrombosis of the false lumen (white arrow) and decreased
AC C
EP
TE D
aneurysm size.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
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EP
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M AN U
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