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Claus J, Schoof L, Mir TS, Kammal AL, Schön G, Kutsche K, Behrendt CA, Kallenbach K, Kölbel T, Kubisch C, Demal TJ, Petersen J, Brickwedel J, Hübler M, Detter C, Kirchhof P, Debus ES, Rybczynski M, von Kodolitsch Y. Late diagnosis of Marfan syndrome is associated with unplanned aortic surgery and cardiovascular death. J Thorac Cardiovasc Surg 2025; 169:1201-1209.e33. [PMID: 39306029 DOI: 10.1016/j.jtcvs.2024.09.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/27/2024] [Accepted: 09/05/2024] [Indexed: 10/17/2024]
Abstract
BACKGROUND Marfan syndrome (MFS) guidelines recommend optimal pharmacologic therapy (OPT) and replacement of the ascending aorta (RAA) at 5.0 cm in diameter to prevent acute type A aortic dissection (ATAAD) and death. The effect of early MFS diagnosis and initiation of therapy on outcomes is not known. Therefore, we sought to evaluate the effect of age at MFS diagnosis and therapy initiation on delayed RAA and death. METHODS This retrospective observational cohort study with long-term follow-up included consecutive patients with MFS, pathogenic FBN1 variant, and regular visits to a European Reference Network Center. We considered MFS diagnosis at age ≥21 years late and OPT initiation at age <21 years early. Outcomes were delayed RAA with aneurysm diameter >5.0 cm or ATAAD and death from all causes. We used landmark design starting at age 21 years to determine associations with outcomes. RESULTS The study group consisted of 288 patients (45.1% male), including 169 patients with late diagnosis of MFS (58.7%) and 63 with early OPT (21.9%). During mean follow-up of 25 ± 14.7 years, 78 patients had delayed RAA, with 42 operations for ATAAD and 36 for aneurysms ≥5.0 cm. There were 33 deaths, including 11 deaths late after ATAAD. All deaths were cardiovascular. Late diagnosis, but not early OPT, showed univariate association with delayed RAA (P < .001) and death (P = .025). Multivariate Cox regression analysis confirmed late diagnosis as predictor of delayed RAA (hazard ratio, 8.01; 95% confidence interval, 2.52-25.45; P < .001) and death (hazard ratio, 4.68; 95% confidence interval, 1.17-18.80; P = .029). CONCLUSIONS Late diagnosis of MFS is associated with delayed surgery and death.
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Affiliation(s)
- Jason Claus
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany
| | - Lauritz Schoof
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany
| | - Thomas S Mir
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; Division of Cardiology, VASCERN-HTAD Affiliated Partner-Centre, Hamburg, Germany
| | - Anna Lena Kammal
- Department of Legal Medicine, All University Medical Center Eppendorf, Hamburg, Germany
| | - Gerhard Schön
- Division Medical Biometry, Institute of Medical Biometry and Epidemiology, All University Medical Center Eppendorf, Hamburg, Germany
| | - Kerstin Kutsche
- Institute of Human Genetics, All University Medical Center Eppendorf, Hamburg, Germany
| | - Christian-Alexander Behrendt
- Division of Vascular Medicine, Asklepios Clinic Wandsbek, Asklepios Medical School, Hamburg, Germany; Division of Cardiology, VASCERN-HTAD Affiliated Partner-Centre, Hamburg, Germany
| | - Klaus Kallenbach
- Division of Heart Surgery, Centre Hospitalier Luxembourg, Haerz-Zenter Luxemburg, VASCERN-HTAD-Affiliated Partner-Centre, Luxembourg
| | - Tilo Kölbel
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany
| | - Christian Kubisch
- Institute of Human Genetics, All University Medical Center Eppendorf, Hamburg, Germany; Division of Cardiology, VASCERN-HTAD Affiliated Partner-Centre, Hamburg, Germany
| | - Till Joscha Demal
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner-Site Hamburg/&Kiel/Lübeck, Hamburg, Germany
| | - Johannes Petersen
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner-Site Hamburg/&Kiel/Lübeck, Hamburg, Germany
| | - Jens Brickwedel
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany
| | - Michael Hübler
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany
| | - Christian Detter
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany
| | - Paulus Kirchhof
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; German Center for Cardiovascular Research (DZHK), Partner-Site Hamburg/&Kiel/Lübeck, Hamburg, Germany; College of Medical and Dental Sciences, Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Eike Sebastian Debus
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; Division of Cardiology, VASCERN-HTAD Affiliated Partner-Centre, Hamburg, Germany
| | - Meike Rybczynski
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; Division of Cardiology, VASCERN-HTAD Affiliated Partner-Centre, Hamburg, Germany
| | - Yskert von Kodolitsch
- Division of Cardiology, Heart Surgery and Vascular Surgery, University Heart & Vascular Center Hamburg, All University Medical Center Eppendorf, Hamburg, Germany; Division of Cardiology, VASCERN-HTAD Affiliated Partner-Centre, Hamburg, Germany.
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Deng CH, Zhou Y, Chen J, He GF, Fu QS, Li JM, Wang G, Hu XD. Diagnostic and therapeutic considerations for primary penal synovial sarcoma with specific MDM2 gene amplification: A case report. World J Clin Urol 2025; 14. [DOI: 10.5410/wjcu.v14.i1.104791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2025] [Revised: 02/23/2025] [Accepted: 03/08/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND
Primary renal synovial sarcoma (PRSS) is extremely rare in clinical practice, and most cases are associated with SYT-SSX gene fusion. The PRSS with specific MDM2 gene amplification has not been reported so far. Therefore, there is no practical experience regarding the clinical, pathological features and diagnosis and treatment plans for patients of this type. This article reports a case of PRSS with specific MDM2 gene amplification.
CASE SUMMARY
The patient was preoperatively diagnosed with a malignant tumor of the left kidney (with a high probability of clear cell carcinoma). During the operation, a radical left nephrectomy was performed. The postoperative pathological examination report confirmed synovial sarcoma, and the gene test suggested PRSS with specific MDM2 gene amplification. Forty-eight days after the operation, the patient presented with "abdominal distension and diarrhea" and was found to have a huge metastatic tumor in the original left renal area. The patient died clinically 17 hours after admission due to "multiple organ failure".
CONCLUSION
PRSS with MDM2 gene amplification has a poorer prognosis, a higher degree of malignancy, and a faster progression, and clinicians need to be highly vigilant.
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Affiliation(s)
- Chao-Hua Deng
- Department of Urology, The Fourth Affiliated Hospital of Dali University, Chuxiong 675000, Yunnan Province, China
| | - Yuan Zhou
- Department of Urology, The Fourth Affiliated Hospital of Dali University, Chuxiong 675000, Yunnan Province, China
| | - Jing Chen
- Department of Nuclear Magnetic Resonance, The Fourth Affiliated Hospital of Dali University, Chuxiong 675000, Yunnan Province, China
| | - Guo-Fu He
- Department of Computed Tomography, The Fourth Affiliated Hospital of Dali University, Chuxiong 675000, Yunnan Province, China
| | - Qun-Shan Fu
- Department of Pathology, The Fourth Affiliated Hospital of Dali University, Chuxiong 675000, Yunnan Province, China
| | - Jiong-Ming Li
- The Third Ward of Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming 675000, Yunnan Province, China
| | - Guang Wang
- The Third Ward of Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming 675000, Yunnan Province, China
| | - Xiao-Dong Hu
- Department of Urology, The Fourth Affiliated Hospital of Dali University, Chuxiong 675000, Yunnan Province, China
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Korkontzelos I, Kotsia A, Mpourazanis G, Natsios A, Korkontzelou PD, Karanikis P, Pappa E, Papalexis P. Marfan Syndrome Associated With Acute Myocardial Infarction in the First Trimester of Pregnancy. Cureus 2024; 16:e59182. [PMID: 38807841 PMCID: PMC11130601 DOI: 10.7759/cureus.59182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/28/2024] [Indexed: 05/30/2024] Open
Abstract
Marfan syndrome (MFS) is a rare hereditary connective tissue disorder with autosomal dominant inheritance associated with an increased risk of cardiovascular complications due to connective tissue fragility. Acute myocardial infarction during pregnancy is also a rare event associated with poor maternal and fetal outcomes. Herein, we report a case of a 30-year-old pregnant woman with a known history of MFS. The patient had been treated surgically for an ascending aorta aneurysm and mechanical prosthetic aortic valve repair. She presented at 12 weeks of gestation with severe chest pain, which proved to be acute myocardial infarction. This is believed to be the first case of this complex medical condition presented in the first trimester of pregnancy.
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Affiliation(s)
- Ioannis Korkontzelos
- Department of Obstetrics and Gynecology, Ioannina State General Hospital "G. Chatzikosta", Ioannina, GRC
| | - Anna Kotsia
- Department of Cardiology, Ioannina State General Hospital "G. Chatzikosta", Ioannina, GRC
| | - George Mpourazanis
- Department of Obstetrics and Gynecology, Ioannina State General Hospital "G. Chatzikosta", Ioannina, GRC
| | - Angelos Natsios
- Department of Obstetrics and Gynecology, Ioannina State General Hospital "G. Chatzikosta", Ioannina, GRC
| | | | - Pavlos Karanikis
- Department of Cardiology, Ioannina State General Hospital "G. Chatzikosta", Ioannina, GRC
| | - Evgenia Pappa
- Department of Cardiology, Ioannina State General Hospital "G. Chatzikosta", Ioannina, GRC
| | - Petros Papalexis
- Department of Endocrinology, First Department of Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, GRC
- Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, GRC
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Fernandez Campos BA, Silversides CK. Marfan syndrome and pregnancy-related aortic complications: contemporary outcomes from two Spanish Marfan units. REVISTA ESPANOLA DE CARDIOLOGIA (ENGLISH ED.) 2022; 75:542-544. [PMID: 35339410 DOI: 10.1016/j.rec.2022.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 12/21/2021] [Indexed: 06/14/2023]
Affiliation(s)
- Beatriz Aldara Fernandez Campos
- University of Toronto, Division of Cardiology, Toronto Congenital Cardiac Centre for Adults, University Health Network and Mount Sinai Hospital, Toronto, Canada
| | - Candice K Silversides
- University of Toronto, Division of Cardiology, Toronto Congenital Cardiac Centre for Adults, University Health Network and Mount Sinai Hospital, Toronto, Canada.
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Fernandez Campos BA, Silversides CK. Síndrome de Marfan y complicaciones aórticas en el embarazo. Resultados contemporáneos de dos unidades de Marfan españolas. Rev Esp Cardiol 2022. [DOI: 10.1016/j.recesp.2021.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Curtis SL, Swan L. Aortopathy in pregnancy. BRITISH HEART JOURNAL 2022; 108:1851-1857. [PMID: 35144984 DOI: 10.1136/heartjnl-2021-319828] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Accepted: 01/12/2022] [Indexed: 11/04/2022]
Abstract
Aortic dissection is one of the most common causes of death in pregnancy. Most cases are caused by hereditary thoracic aortopathy (HTA), and women are often unaware they are at risk. Awareness, early recognition and involvement of senior clinicians from the expert cardio-obstetric team are essential to facilitate early diagnosis and carefully planned and coordinated antenatal and postnatal care. Frequent imaging antenatally and good blood pressure control are key. Delivery needs particular attention with optimal pain control and techniques to minimise maternal effort. Dissection is most common post partum and a period of close surveillance with meticulous blood pressure control after delivery is crucial, as well as follow-up of the baby in paediatric services. All women with a family history of aortic dissection or sudden death should be investigated. Women with known HTA should be offered specialist individualised pre-pregnancy counselling, including advice about genetics and inheritance, before starting a family. Future research is directed towards more individualised risk assessment, pre-pregnancy advice and pharmacological options to reduce dissection risk.
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Affiliation(s)
| | - Lorna Swan
- Department of Adult Congenital Heart Disease, Golden Jubilee National Hospital West of Scotland Regional Heart and Lung Centre, Glasgow, UK
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Ramage K, Grabowska K, Silversides C, Quan H, Metcalfe A. Maternal, pregnancy, and neonatal outcomes for women with Marfan syndrome. Birth Defects Res 2020; 112:1802-1808. [PMID: 33118709 DOI: 10.1002/bdr2.1829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 09/21/2020] [Accepted: 10/12/2020] [Indexed: 11/09/2022]
Abstract
BACKGROUND Marfan syndrome (MFS) is an autosomal dominant hereditary disorder which affects cardiovascular structure and function. With medical advances, more women with MFS experience pregnancy, which may increase maternal and neonatal risk. Existing research has been limited by small or clinical samples. This study examines the association of MFS and adverse maternal, neonatal, and obstetric outcomes. METHODS We conducted a cross-sectional study using the discharge abstract database, containing all labor and delivery hospitalizations in Canada (excluding Quebec) from fiscal years 2004-2015 where women delivered a live- or stillbirth. We measured maternal and neonatal morbidity, preterm births (<37 weeks), small-for-gestational-age births, perinatal mortality, and adverse maternal cardiovascular events. For each outcome, we calculated the absolute risk for women with and without MFS and used generalized estimating equations with a logit function to calculate odds. RESULTS Overall, 2,682,461 women delivered a live or stillborn infant in Canada during the study period, with 135 birth events to women with MFS. Women with MFS did not have significantly higher odds of severe maternal morbidity during their delivery (aOR:1.3; 95%CI: 0.4-4.0). Similarly, their infants did not have significantly higher odds of neonatal morbidity. However, infants born to women with MFS were significantly more likely to be born preterm (aOR:2.6; 95%CI: 1.6-4.3) and to be small-for-gestational-age (aOR:1.8; 95%CI:1.0-3.1). CONCLUSIONS This population-based study indicates that, although some women with MFS may experience higher odds of maternal and/or neonatal morbidity during labor and delivery, the majority of women with MFS can have healthy births with proper clinical management.
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Affiliation(s)
- Kaylee Ramage
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Kirsten Grabowska
- Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| | | | - Hude Quan
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Amy Metcalfe
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.,Department of Medicine, University of Calgary, Calgary, Alberta, Canada.,Department of Obstetrics & Gynaecology, University of Calgary, Calgary, Alberta, Canada
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Ma WG, Zhu JM, Chen Y, Qiao ZY, Ge YP, Li CN, Zheng J, Liu YM, Sun LZ. Aortic dissection during pregnancy and postpartum in patients with Marfan syndrome: a 21-year clinical experience in 30 patients. Eur J Cardiothorac Surg 2020; 58:294-301. [PMID: 32259204 DOI: 10.1093/ejcts/ezaa048] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 01/14/2020] [Accepted: 01/31/2020] [Indexed: 01/15/2023] Open
Abstract
Abstract
OBJECTIVES
Pregnancy-related aortic dissection (AoD) in Marfan syndrome is a lethal catastrophe. Due to its rarity and limited clinical experience, there is no consensus regarding the optimal management strategy. We seek to present our 21-year experience in such patients , focusing on management strategies and early and late outcomes.
METHODS
Between 1998 and 2019, we managed 30 pregnant women with Marfan syndrome (mean age 30.7 ± 4.3 years) who sustained AoD at a mean of 28.3 ± 8.8 weeks of gestation (GWs). AoD was acute in 21 (70%), type A (TAAD) in 24 (80%) and type B (TBAD) in 6 (20%). Fourteen TAADs (58.3%, 14/24) and 2 TBADs (33.3%, 2/6) occurred in the third trimester or postpartum. The maximal aortic size was < 45 mm in 26.7% (8/30; 3 TAADs, 5 TBADs). Management strategy was based on the types of dissection and GWs (i.e. surgical versus medical treatment, surgery or delivery first).
RESULTS
TAADs were treated medically in 1 and surgically in 23. The timing of delivery and surgery were caesarean first at 35.4 ± 6.1 GWs in 7 (29.2%), followed by surgery after mean 46 days; single-stage C-section and surgery at 32.0 ± 5.0 GWs in 10 (41.7%); and surgery first at 18.0 ± 5.8 GWs in 6 (25%), followed by C-section after 20 days. Maternal and foetal mortality were 28.6% (2/7) and 14.3% (1/7), 10.0% (1/10) and 20.0% (2/10) and 16.7% (1/6) and 83.3% (5/6), respectively. Five TBADs (83.3%) were managed with C-section followed by surgery in 2 and medical treatment in 3. The respective maternal and foetal mortality were 50% (1/2) and 100% (2/2) and 33.3% (1/3) and 33.3% (1/3), respectively. One TBAD was managed surgically first followed by C-section, resulting in maternal survival and foetal death. Follow-up was complete in 95.8% (23/24) at 3.7 ± 2.9 years. Four late deaths occurred and reoperation was performed in 1 patient. Maternal and foetal survival were 64.3% and 54.1% at 6 years, respectively.
CONCLUSIONS
Management of AoD in pregnant women with Marfan syndrome should be based on types of dissection (surgical versus medical) and gestational age (delivery or surgery first), which largely determine maternal and foetal survival. Aortic repair should be considered prior to conception in women with Marfan syndrome even at diameters smaller than recommended by current guidelines.
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Affiliation(s)
- Wei-Guo Ma
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Jun-Ming Zhu
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Yu Chen
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Zhi-Yu Qiao
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Yi-Peng Ge
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Cheng-Nan Li
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Jun Zheng
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Yong-Min Liu
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
| | - Li-Zhong Sun
- Department of Cardiovascular Surgery, Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Diseases, Capital Medical University, Beijing, China
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Minsart AF, Mongeon FP, Laberge AM, Morin F, Dore A, Leduc L. Obstetric and cardiac outcomes in women with Marfan syndrome and an aortic root diameter ≤ 45mm. Eur J Obstet Gynecol Reprod Biol 2018; 230:68-72. [DOI: 10.1016/j.ejogrb.2018.09.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 08/10/2018] [Accepted: 09/10/2018] [Indexed: 01/16/2023]
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