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Sakaguchi K, Nakai H, Tsujimoto T, Kono A, Koda Y, Yamanaka K, Okada K. Two-stage surgery for acute type B aortic dissection and aortic root aneurysm in a patient with Turner syndrome: a case report. GENERAL THORACIC AND CARDIOVASCULAR SURGERY CASES 2025; 4:23. [PMID: 40312389 PMCID: PMC12046644 DOI: 10.1186/s44215-025-00202-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Accepted: 03/19/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND Patients with Turner syndrome are at high risk of aortic dissection and are more likely to present with fatal outcomes. Turner syndrome is classified as a heritable thoracic aortic disease in the latest EACTS/STS guidelines. Herein, we present a case of two-staged surgery for acute type B aortic dissection and aortic root aneurysm in a patient with Turner syndrome. CASE PRESENTATION A 29-year-old female patient with Turner syndrome was admitted to our center due to back pain and was diagnosed with acute type B aortic dissection. Echocardiography revealed a dilated aortic root with bicuspid aortic valve. On the 5 th day after admission, the patient presented with a higher level of back pain. Follow-up computed tomography scan revealed changes from two- to three-channel aortic dissection a further aortic dilation. Therefore, descending aorta and partial aortic arch replacement were initially performed. Then, valve-sparing aortic root replacement and residual arch replacement were performed 3 months after the first surgery. Postoperative echocardiography confirmed the absence of aortic regurgitation. The patient was discharged on the 17th postoperative day without any complications. CONCLUSIONS Two-stage surgery was successfully performed for the thoracic aorta and aortic root aneurysms in a patient with Turner syndrome. The patient recovered for 3 months after the left thoracotomy surgery and underwent a two-stage surgery through a median sternotomy surgery with good surgical results.
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Affiliation(s)
- Kazunori Sakaguchi
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan
| | - Hidekazu Nakai
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan
| | - Takanori Tsujimoto
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan
| | - Atsunori Kono
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan
| | - Yojiro Koda
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan
| | - Katsuhiro Yamanaka
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan
| | - Kenji Okada
- Division of Cardiovascular Surgery, Department of Surgery, Kobe University Graduate School of Medicine, 7 - 5- 2 Kusunoki-cho, Kobe, Japan.
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Maternal cardiovascular morbidity and mortality associated with pregnancy in individuals with Turner syndrome: a committee opinion. Fertil Steril 2024; 122:612-621. [PMID: 38980250 DOI: 10.1016/j.fertnstert.2024.06.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 06/04/2024] [Indexed: 07/10/2024]
Abstract
In individuals with Turner syndrome, the risk of death from aortic dissection or rupture during pregnancy may be as high as 1%, and it is unclear whether this risk persists during the postpartum period owing to pregnancy-related aortic changes. Turner syndrome is a relative contraindication for pregnancy; however, it is an absolute contraindication for pregnancy in a patient with an aortic size index of >2.5 cm/m2 or an aortic size index of ≥2.0 cm/m2 with a documented cardiac anomaly or other risk factors. This document replaces the 2012 document of the same name.
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Ribeiro E, Cardenas DAC, Dias FM, Krieger JE, Gutierrez MA. Explainable artificial intelligence in deep learning-based detection of aortic elongation on chest X-ray images. EUROPEAN HEART JOURNAL. DIGITAL HEALTH 2024; 5:524-534. [PMID: 39318689 PMCID: PMC11417491 DOI: 10.1093/ehjdh/ztae045] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 06/03/2024] [Accepted: 06/16/2024] [Indexed: 09/26/2024]
Abstract
Aims Aortic elongation can result from age-related changes, congenital factors, aneurysms, or conditions affecting blood vessel elasticity. It is associated with cardiovascular diseases and severe complications like aortic aneurysms and dissection. We assess qualitatively and quantitatively explainable methods to understand the decisions of a deep learning model for detecting aortic elongation using chest X-ray (CXR) images. Methods and results In this study, we evaluated the performance of deep learning models (DenseNet and EfficientNet) for detecting aortic elongation using transfer learning and fine-tuning techniques with CXR images as input. EfficientNet achieved higher accuracy (86.7% ± 2.1), precision (82.7% ± 2.7), specificity (89.4% ± 1.7), F1 score (82.5% ± 2.9), and area under the receiver operating characteristic (92.7% ± 0.6) but lower sensitivity (82.3% ± 3.2) compared with DenseNet. To gain insights into the decision-making process of these models, we employed gradient-weighted class activation mapping and local interpretable model-agnostic explanations explainability methods, which enabled us to identify the expected location of aortic elongation in CXR images. Additionally, we used the pixel-flipping method to quantitatively assess the model interpretations, providing valuable insights into model behaviour. Conclusion Our study presents a comprehensive strategy for analysing CXR images by integrating aortic elongation detection models with explainable artificial intelligence techniques. By enhancing the interpretability and understanding of the models' decisions, this approach holds promise for aiding clinicians in timely and accurate diagnosis, potentially improving patient outcomes in clinical practice.
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Affiliation(s)
- Estela Ribeiro
- Heart Institute (InCor), Clinics Hospital University of Sao Paulo Medical School (HCFMUSP), Av. Dr. Enéas Carvalho de Aguiar, 44 - Cerqueira César, São Paulo, SP 05403-900, Brazil
- University of Sao Paulo Medical School (FMUSP), Av. Dr. Arnaldo, 455 - Cerqueira César, Pacaembu, SP 01246-903, Brazil
| | - Diego A C Cardenas
- Heart Institute (InCor), Clinics Hospital University of Sao Paulo Medical School (HCFMUSP), Av. Dr. Enéas Carvalho de Aguiar, 44 - Cerqueira César, São Paulo, SP 05403-900, Brazil
| | - Felipe M Dias
- Heart Institute (InCor), Clinics Hospital University of Sao Paulo Medical School (HCFMUSP), Av. Dr. Enéas Carvalho de Aguiar, 44 - Cerqueira César, São Paulo, SP 05403-900, Brazil
- Polytechnique School, University of Sao Paulo (POLI USP), Av. Prof. Luciano Gualberto, 380 - Butantã, São Paulo, SP 05508-010, Brazil
| | - Jose E Krieger
- Heart Institute (InCor), Clinics Hospital University of Sao Paulo Medical School (HCFMUSP), Av. Dr. Enéas Carvalho de Aguiar, 44 - Cerqueira César, São Paulo, SP 05403-900, Brazil
| | - Marco A Gutierrez
- Heart Institute (InCor), Clinics Hospital University of Sao Paulo Medical School (HCFMUSP), Av. Dr. Enéas Carvalho de Aguiar, 44 - Cerqueira César, São Paulo, SP 05403-900, Brazil
- University of Sao Paulo Medical School (FMUSP), Av. Dr. Arnaldo, 455 - Cerqueira César, Pacaembu, SP 01246-903, Brazil
- Polytechnique School, University of Sao Paulo (POLI USP), Av. Prof. Luciano Gualberto, 380 - Butantã, São Paulo, SP 05508-010, Brazil
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Hu S, Liu J, Tang H, Xie X, Wei Y. Refractory hypertension complicated with Turner syndrome: A case report. Open Life Sci 2024; 19:20220934. [PMID: 39119483 PMCID: PMC11306959 DOI: 10.1515/biol-2022-0934] [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] [Received: 02/26/2024] [Revised: 07/01/2024] [Accepted: 07/09/2024] [Indexed: 08/10/2024] Open
Abstract
Hypertension is commonly classified into essential hypertension and secondary hypertension, although definitive classification can be challenging in some cases. Here, we discussed a patient who admitted for refractory hypertension, exhibiting various clinical manifestations including inadequate estrogen secretion, underdeveloped secondary sexual characteristics, primary amenorrhea, short stature, multiple moles, and somatic abnormalities. The patient was finally diagnosed with Turner syndrome (TS) based on clinical findings and chromosomal analysis. The genetic karyotype identified was 46,X,i(X)(q10).
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Affiliation(s)
- Sisi Hu
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, China
| | - Jichun Liu
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, China
| | - Haixia Tang
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, China
| | - Xiangrong Xie
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, China
| | - Youquan Wei
- Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui, China
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Suntratonpipat S, Pajunen K, Rosolowsky E, Escudero CA, Girgis R, Thompson RB, Pagano JJ, Tham EB. Cardiac MRI evaluation of aortic biophysical properties in paediatric Turner syndrome. Cardiol Young 2024; 34:1764-1770. [PMID: 38606642 DOI: 10.1017/s1047951124000799] [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] [Indexed: 04/13/2024]
Abstract
BACKGROUND Aortopathy in Turner syndrome is associated with aortic dilation, and the risk of dissection is increased when the aortic size index is ≥ 2-2.5 cm/m2. We evaluated the aortic biophysical properties in paediatric Turner syndrome using cardiac MRI to determine their relationship to aortic size index. METHODS Turner syndrome patients underwent cardiac MRI to evaluate ventricular function, aortic dimensions, and biophysical properties (aortic stiffness index, compliance, distensibility, pulse wave velocity, and aortic and left ventricular elastance). Spearman correlation examined correlations between these properties and aortic size index. Data was compared to 10 controls. RESULTS Of 25 Turner syndrome patients, median age 14.7 years (interquartile range: 11.0-16.8), height z score -2.7 (interquartile range: -2.92 - -1.54), 24% had a bicuspid aortic valve. Turner syndrome had increased diastolic blood pressure (p < 0.001) and decreased left ventricular end-diastolic (p < 0.001) and end-systolic (p = 0.002) volumes compared to controls. Median aortic size index was 1.81 cm/m2 (interquartile range: 1.45-2.1) and 7 had an aortic size index > 2 cm/m2. Aortic and left ventricular elastance were greater in Turner syndrome compared to controls (both p < 0.001). Increased aortic size index correlated with increased aortic elastance (r = 0.5, p = 0.01) and left ventricular elastance (r = 0.59, p = 0.002) but not aortic compliance. Higher ascending aortic areas were associated with increased aortic compliance (r = 0.44, p = 0.03) and left ventricular elastance (r = 0.49, p = 0.01). CONCLUSION Paediatric Turner syndrome with similar aortic size index to controls showed MRI evidence of abnormal aortic biophysical properties. These findings point to an underlying aortopathy and provide additional parameters that may aid in determining risk factors for aortic dissection.
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Affiliation(s)
- Somjate Suntratonpipat
- Division of Pediatric Cardiology, Stollery Children's Hospital & Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
| | - Kiera Pajunen
- Division of Pediatric Cardiology, Stollery Children's Hospital & Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
| | - Elizabeth Rosolowsky
- Division of Pediatric Endocrinology, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada
| | - Carolina A Escudero
- Division of Pediatric Cardiology, Stollery Children's Hospital & Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
| | - Rose Girgis
- Division of Pediatric Endocrinology, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada
| | - Richard B Thompson
- Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada
| | - Joseph J Pagano
- Division of Pediatric Cardiology, Stollery Children's Hospital & Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
| | - Edythe B Tham
- Division of Pediatric Cardiology, Stollery Children's Hospital & Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada
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Ceuppens AS, De Meester P, Van De Bruaene A, Voigt JU, Van Calsteren K, Budts W, Troost E. Aorta pathology and pregnancy-related risks in adult congenital cardiac disease: does the aorta dilate during pregnancy? Obstet Med 2024; 17:41-46. [PMID: 38660320 PMCID: PMC11037198 DOI: 10.1177/1753495x231156851] [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: 11/14/2022] [Accepted: 01/20/2023] [Indexed: 04/26/2024] Open
Abstract
Background Aortic dilatation and pregnancy are major concerns in women with aortopathy (AOP). This single-centre retrospective analysis focuses on the evolution of aortic diameters during and after pregnancy in women with Marfan syndrome (MS), Turner syndrome (TS) and bicuspid aortic valve (BAV) aortopathy. Methods and results Thirty-eight women who had one or more single pregnancies were included. The ascending aorta was measured during pregnancy and postpartum. During pregnancy, a significant increase of diameters of the sinus aortae (median 1.4 mm; [-1.3; 3.8]) and ascending aorta (median 2.1 mm; [0.0; 4.0]) was noted. Systemic hypertension gives dilation of the aorta, but it did not influence the overall trajectory during pregnancy. Conclusion Significant aortic dilatation is noted during pregnancy in women with underlying AOP, even persisting in the long term. Pre-existing systemic hypertension is associated with larger aortic diameters prior to pregnancy. More research on a larger study population however is needed.
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Affiliation(s)
| | - Pieter De Meester
- Congenital and Structural Cardiology, University Hospitals Leuven, Belgium
- Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Belgium
| | - Alexander Van De Bruaene
- Congenital and Structural Cardiology, University Hospitals Leuven, Belgium
- Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Belgium
| | - Jens-Uwe Voigt
- Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Belgium
- Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium
| | | | - Werner Budts
- Congenital and Structural Cardiology, University Hospitals Leuven, Belgium
- Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Belgium
- Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium
| | - Els Troost
- Congenital and Structural Cardiology, University Hospitals Leuven, Belgium
- Department of Cardiovascular Sciences, KU Leuven – University of Leuven, Belgium
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McCarrison S, Carr A, Wong SC, Mason A. The prevalence of hypertension in paediatric Turner syndrome: a systematic review and meta-analysis. J Hum Hypertens 2023; 37:675-688. [PMID: 36471031 PMCID: PMC10403354 DOI: 10.1038/s41371-022-00777-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 10/21/2022] [Accepted: 11/08/2022] [Indexed: 12/10/2022]
Abstract
Cardiovascular related deaths account for over 40% of the excess mortality in Turner syndrome (TS). Hypertension, a modifiable risk factor for both aortic dilatation and dissection, is more commonly encountered in TS during childhood and adolescence. Treatment of hypertension is currently recommended beyond the age of 16 years in TS to help reduce the risk of aortic dissection. This study aims to determine the prevalence of hypertension in paediatric patients with TS and explore the associated methodologies of blood pressure evaluation reported in these studies. Three online databases were searched (Medline, Embase and Web of Science) for literature which reported a prevalence, or allowed calculation of prevalence, of hypertension in patients with TS who were 18 years of age or younger. Seventeen studies which met the primary eligibility criteria, with a total of 1948 patients, were included. The estimated pooled prevalence of hypertension in children and adolescents with TS was 16% (95% CI: 8.9-24.6%). There was significant heterogeneity detected between the studies. The prevalence of hypertension in those studies which assessed 24-h Ambulatory Blood Pressure Monitoring (ABPM) was 21.1% (95% CI: 15.2-27.6%) compared those which used another method of blood pressure measurement which was 13.5% (95% CI: 5.2-24.4%). Given the impact of hypertension with long-term health outcomes and the reversibility of these same outcomes by addressing abnormal blood pressure, prompt and early diagnosis of hypertension in young girls with TS should be prioritised. We recommend the use of 24-h ABPM in screening for hypertension in the paediatric TS population.
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Affiliation(s)
- Sarah McCarrison
- Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK
| | - Aoife Carr
- School of Medicine, University of Glasgow, Glasgow, UK
| | - Sze Choong Wong
- Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK
| | - Avril Mason
- Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK.
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Abstract
PURPOSE OF REVIEW Structural genomic variants have emerged as a relevant cause for several disorders, including intellectual disability, neuropsychiatric disorders, cancer and congenital heart disease. In this review, we will discuss the current knowledge about the involvement of structural genomic variants and, in particular, copy number variants in the development of thoracic aortic and aortic valve disease. RECENT FINDINGS There is a growing interest in the identification of structural variants in aortopathy. Copy number variants identified in thoracic aortic aneurysms and dissections, bicuspid aortic valve related aortopathy, Williams-Beuren syndrome and Turner syndrome are discussed in detail. Most recently, the first inversion disrupting FBN1 has been reported as a cause for Marfan syndrome. SUMMARY During the past 15 years, the knowledge on the role of copy number variants as a cause for aortopathy has grown significantly, which is partially due to the development of novel technologies including next-generation sequencing. Although copy number variants are now often investigated on a routine basis in diagnostic laboratories, more complex structural variants such as inversions, which require the use of whole genome sequencing, are still relatively new to the field of thoracic aortic and aortic valve disease.
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Affiliation(s)
- Josephina A.N. Meester
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
| | - Anne Hebert
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
| | - Bart L. Loeys
- Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium
- Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
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Meccanici F, de Bruijn JWC, Dommisse JS, Takkenberg JJM, van den Bosch AE, Roos-Hesselink JW. Prevalence and development of aortic dilation and dissection in women with Turner syndrome: a systematic review and meta-analysis. Expert Rev Cardiovasc Ther 2023; 21:133-144. [PMID: 36688313 DOI: 10.1080/14779072.2023.2172403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
OBJECTIVES Women with Turner syndrome (TS) have an increased risk of aortic disease, reducing life-expectancy. This study aimed to systematically review the prevalence of thoracic aortic dilatation, aortic dimensions and growth, and the incidence of aortic dissection. METHODS A systematic literature search was conducted up to July 2022. Observational studies with an adult TS population were included, and studies including children aged <15 years old or specific TS populations were excluded. RESULTS In total 21 studies were included. The pooled prevalence of ascending aortic dilatation was 23% (95% CI 19-26) at a mean pooled age of 29 years (95% CI 26-32), while the incidence of aortic dissection was 164 per 100.000 patient-years (95% CI 95-284). Three reporting studies showed aortic growth over time to be limited. Risk factors for aortic dilation or dissection were older age, bicuspid aortic valve, aortic coarctation, and hypertension. CONCLUSION In adult TS women, ascending aortic dilatation is common and the hazard of aortic dissection increased compared to the general population, whereas aortic growth is limited. Conventional risk markers do not explain all aortic dissection cases; therefore, new imaging parameters and blood biomarkers are needed to improve prediction, allowing for patient-tailored follow-up and surgical decision-making.
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Affiliation(s)
- F Meccanici
- Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - J W C de Bruijn
- Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - J S Dommisse
- Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - J J M Takkenberg
- Department of Cardiothoracic Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - A E van den Bosch
- Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - J W Roos-Hesselink
- Department of Cardiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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Jones L, Blair J, Hawcutt DB, Lip GYH, Shantsila A. Hypertension in Turner syndrome: a review of proposed mechanisms, management and new directions. J Hypertens 2023; 41:203-211. [PMID: 36583347 DOI: 10.1097/hjh.0000000000003321] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Acquired cardiovascular diseases account for much of the increased risk of premature death in patients with Turner syndrome (TS). Hypertension is a major modifiable cardiovascular risk factor. It has a high prevalence in TS developing at an early age and thus leading to prolonged exposure to high blood pressure. The aetiology for hypertension in TS is largely unknown. It is likely multifactorial, and recent hypotheses include altered sympathetic tone, vasculopathy and endocrine factors. In this review article we aim to provide a comprehensive review of data on mechanisms of hypertension in TS and their implication for diagnostics and optimal choice of antihypertensive treatments. Ultimately this knowledge should help prevent hypertension-related complications, and improve quality of life and life expectancy for patients with TS.
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Affiliation(s)
- Lily Jones
- Department of Women's and Children's Health, University of Liverpool
| | - Joanne Blair
- Department of Endocrinology, Alder Hey Children's NHS Foundation Trust
| | - Daniel B Hawcutt
- Department of Women's and Children's Health, University of Liverpool
- NIHR Alder Hey Clinical Research Facility, Alder Hey Children's NHS Foundation Trust
| | - Gregory Y H Lip
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
| | - Alena Shantsila
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, UK
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11
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Meccanici F, Schotte MH, Snoeren M, Bons LR, van den Hoven AT, Kardys I, Budde RPJ, van den Bosch AE, Duijnhouwer AL, Roos-Hesselink JW. Aortic dilation and growth in women with Turner syndrome. HEART (BRITISH CARDIAC SOCIETY) 2022; 109:102-110. [PMID: 35705330 DOI: 10.1136/heartjnl-2022-320922] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 05/27/2022] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Women with Turner syndrome (TS) are at increased risk of aortic dissection, which is a life-threatening event associated with aortic dilation. Knowledge on the development of aortic dilation over time remains limited. This study aims to describe the prevalence of aortic dilation, to find associated factors and to study aortic growth in women with TS. METHODS In this prospective multicentre cohort study, consecutive adult women with genetically proven TS included between 2014 and 2016 underwent ECG-triggered multiphase CT angiography at baseline and after 3 years. Aortic diameters were measured at seven levels of the thoracic aorta using double oblique reconstruction and indexed for body surface area. Ascending aortic dilation was defined as an aortic size index >20 mm/m2. Aorta-related and cardiovascular events were collected. Statistical analysis included linear and logistic regression and linear mixed effects models. RESULTS The cohort consisted of 89 women with a median age of 34 years (IQR: 24-44). Ascending aortic dilation was found in 38.2% at baseline. At baseline, age (OR: 1.08 (95% CI 1.03 to 1.13), p<0.001), presence of bicuspid aortic valve (BAV) (OR: 7.09 (95% CI 2.22 to 25.9), p=0.002) and systolic blood pressure (OR: 1.06 (95% CI 1.02 to 1.11), p=0.004) were independently associated with ascending aortic dilation. During a median follow-up of 3.0 (2.4-3.6) years (n=77), significant aortic growth was found only at the sinotubular junction (0.20±1.92 mm, p=0.021). No aortic dissection occurred, one patient underwent aortic surgery and one woman died. CONCLUSIONS In women with TS, ascending aortic dilation is common and associated with age, BAV and systolic blood pressure. Aortic diameters were stable during a 3-year follow-up, apart from a significant yet not clinically relevant increase at the sinotubular junction, which may suggest a more benign course of progression than previously reported.
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Affiliation(s)
| | | | - Miranda Snoeren
- Radiology and Nuclear Medicine, Radboudumc, Nijmegen, The Netherlands
| | - Lidia R Bons
- Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | | | - Isabella Kardys
- Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Ricardo P J Budde
- Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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12
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MicroRNA-126-3p/5p and Aortic Stiffness in Patients with Turner Syndrome. CHILDREN (BASEL, SWITZERLAND) 2022; 9:children9081109. [PMID: 35892612 PMCID: PMC9394385 DOI: 10.3390/children9081109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/13/2022] [Accepted: 07/20/2022] [Indexed: 11/28/2022]
Abstract
Background: Turner Syndrome (TS) is a relatively rare X-chromosomal disease with increased cardiovascular morbidity and mortality. This study aimed to identify whether the circulating miR-126-3p/5p are involved in the pathophysiology of vascular dysfunction in TS. Methods: Using the RT-qPCR, the abundance levels of miR-126-3p and miR-126-5p were determined in 33 TS patients and 33 age-matched healthy volunteers (HVs). Vascular screening, including the assessment of blood pressure, pulse wave velocity, augmentation index, aortic deformation, arterial distensibility, and arterial elastance, was conducted in TS patients and HVs. Results: The abundance levels of miR-126-3p and miR-126-5p were significantly higher in TS patients compared to HVs (p < 0.0001). Within the TS cohort, miR-126-3p/5p correlated significantly with aortic deformation (r = 0.47, p = 0.01; r = 0.48, p < 0.01) and arterial distensibility (r = 0.55, p < 0.01; r = 0.48, p < 0.01). In addition, a significant negative correlation was demonstrated between miR-126-3p and arterial elastance (r = −0.48, p = 0.01). The receiver operating characteristic analysis showed that miR-126-3p and miR-126-5p separated the tested groups with high sensitivity and specificity. Conclusions: The abundance levels of miR-126-3p and miR-126-5p were significantly higher in TS patients compared to HVs. Within the TS cohort, a lower abundance level of miR-126-3p and miR-126-5p was linked with a significantly higher aortic stiffness.
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Bačová M, Li P, Arnold L, Dalla-Pozza R, Haas NA, Oberhoffer FS. Cardiovascular Care of Turner Syndrome Women in Germany: Where Do We Stand?—Results from an Online Patient Survey. Healthcare (Basel) 2022; 10:healthcare10030504. [PMID: 35326982 PMCID: PMC8955387 DOI: 10.3390/healthcare10030504] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/02/2022] [Accepted: 03/04/2022] [Indexed: 02/01/2023] Open
Abstract
Background: This study aimed to investigate whether the cardiovascular care of Turner Syndrome (TS) women in Germany is in accordance with the latest clinical practice guidelines established by the 2016 Cincinnati international TS meeting. Methods: An anonymous online questionnaire was created to ask TS subjects about existing cardiovascular conditions and cardiovascular care received. Depending on cardiovascular morbidity and type of medical care received, the fulfillment of the latest clinical practice guidelines for the care of TS women was assessed. Results: 120 TS patients were included in this study. The mean age of TS subjects was 36.79 years. Only 80% of subjects received annual blood pressure measurements within the TS cohort, and only 60% received cardiac imaging according to international clinical practice guidelines. More than 55% of TS women did not feel well informed about TS-specific cardiovascular risk factors by their treating physician. Conclusions: A potential lack of cardiovascular care might be present in TS women in Germany as the results of this online patient survey suggest. The cardiovascular care of TS patients, particularly cardiac imaging and patient education, needs to receive more attention.
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14
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Cauldwell M, Steer PJ, Adamson D, Alexander C, Allen L, Bhagra C, Bolger A, Bonner S, Calanchini M, Carroll A, Casey R, Curtis S, Head C, English K, Hudsmith L, James R, Joy E, Keating N, MacKiliop L, McAuliffe F, Morris RK, Mohan A, Von Klemperer K, Kaler M, Rees DA, Shetty A, Siddiqui F, Simpson L, Stocker L, Timmons P, Vause S, Turner HE. Pregnancies in women with Turner Syndrome: A retrospective multicentre UK study. BJOG 2021; 129:796-803. [PMID: 34800331 DOI: 10.1111/1471-0528.17025] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2021] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To determine the characteristics and outcomes of pregnancy in women with Turner Syndrome DESIGN: Retrospective 20-year cohort study (2000-2020) SETTING: 16 tertiary referral maternity units in the UK POPULATION OR SAMPLE: 81 women with Turner syndrome who became pregnant METHODS: Retrospective chart analysis MAIN OUTCOME MEASURES: Mode of conception, pregnancy outcomes RESULTS: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127 (42.5%)) were by egg donation. Only 9/31 (29%) of pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) with mosaic karyotype 45,X/46,XX (p<0.0001). Women with mosaic 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared to other TS-karyotype groups (p<0.001), and more likely to have a spontaneous menarche (75.8% vs 50% or less, p=0.008). There were 17 miscarriages, 3 terminations of pregnancy, 2 stillbirths and 105 livebirths. Two women had aortic dissection (2.5%); both were 45,X karyotype, with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within six months of delivery. 10/106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) with singleton birthweight/gestational age data weighed <10th centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) of pregnancies was there documentation of cardiovascular imaging within 24 months prior to conceiving. CONCLUSIONS Pregnancy in women with TS is associated with major maternal cardiovascular risks and deserve thorough cardiovascular assessment and counselling prior to assisted or spontaneous pregnancy managed by a specialist team.
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Affiliation(s)
- Matthew Cauldwell
- Department of Obstetrics, Maternal Medicine Service, St George's Hospital, Blackshaw Road, London, SW17 0QT
| | - Philip J Steer
- Academic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, United Kingdom
| | - Dawn Adamson
- Department of Cardiology, University Hospitals Coventry and Warwickshire, United Kingdom
| | | | - Lowri Allen
- Department of Endocrinology, Cardiff, Vale University Health Board
| | - Catriona Bhagra
- Department of Cardiology, Addenbrookes Hospital, Cambridge, United Kingdom
| | - Aidan Bolger
- Department of Adult Congenital Heart Disease, Glenfield Hospital, Leicester, United Kingdom
| | - Samantha Bonner
- Saint Mary's Managed Clinical Service, Manchester University Foundation Trust, Manchester
| | - Matilde Calanchini
- Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust
| | - Aisling Carroll
- Department of Congenital Cardiology, University Hospital Southampton NHS Foundation Trust
| | - Ruth Casey
- Department of Endocrinology, Addenbrookes Hospital, Cambridge
| | - Stephanie Curtis
- Adult Congenital Heart Disease Service, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
| | - Catherine Head
- Cardiology Department, Norwich University Hospital, Norfolk
| | - Kate English
- Department of Adult Congenital Heart Disease, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Lucy Hudsmith
- Department of Adult Congenital Heart Disease, University Hospitals Birmingham
| | - Rachael James
- Department of Cardiology, University Hospitals Sussex, Brighton
| | - Eleanor Joy
- Department of Adult Congenital Heart Disease, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
| | - Niamh Keating
- Department of Obstetrics, UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - Lucy MacKiliop
- Women's Centre, Oxford University Hospitals NHS Foundation Trust, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Fionnuala McAuliffe
- Department of Obstetrics, UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland
| | - R Katie Morris
- Academic Department of Obstetrics, Birmingham Women's and Children's NHS Foundation Trust, University of Birmingham, Edgbaston, Birmingham, B15 2TG, UK
| | - Aarthi Mohan
- Department of Obstetrics, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
| | | | | | - D Aled Rees
- Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, CF24 4HQ, UK
| | - Asha Shetty
- Department of Obstetrics, Aberdeen Royal Infirmary, Scotland
| | - Farah Siddiqui
- Department of Obstetrics, Royal Leicester Infirmary, Leicester, United Kingdom
| | | | | | - Paul Timmons
- Department of Obstetrics, Queen Anne Hospital, Southampton
| | - Sarah Vause
- Department of Adult Congenital Heart Disease, Glenfield Hospital, Leicester, United Kingdom
| | - Helen E Turner
- Saint Mary's Managed Clinical Service, Manchester University Foundation Trust, Manchester
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15
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A Review of Recent Developments in Turner Syndrome Research. J Cardiovasc Dev Dis 2021; 8:jcdd8110138. [PMID: 34821691 PMCID: PMC8623498 DOI: 10.3390/jcdd8110138] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 10/11/2021] [Accepted: 10/14/2021] [Indexed: 12/16/2022] Open
Abstract
Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian failure, congenital heart defects, endocrine disorders, lymphedema, and webbed neck. People with Turner syndrome have significantly increased mortality risk primarily due to cardiovascular abnormalities. The mechanisms that lead to these defects are not completely understood and are obscured by the significant variability of both karyotype and phenotype without consistent correlation between the two. This paper presents a review of the recent literature surrounding the symptoms, mechanisms, diagnosis, and treatment of Turner syndrome with a focus on cardiovascular manifestations. With technological advancements in genetics, the molecular processes of Turner syndrome have begun to be dissected. Certain genes on the X chromosome that typically escape inactivation have been implicated in both specific manifestations and broader risk categories. Recently identified genome-wide epigenetic changes may help explain the variability in presentation. It remains unclear as to how the combination of these factors results in the overall clinical picture, but advances in genomic, genetic, epigenetic, and -omics technology hold promise for providing insights that will improve the medical management of individuals with Turner syndrome.
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16
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Kalashnikova LA, Danilova MS, Gubanova MV, Dreval MV, Dobrynina LA, Chechetkin AO. [Internal carotid artery dissection in patients with Turner's syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova 2021; 121:58-65. [PMID: 34553583 DOI: 10.17116/jnevro202112108258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Cervical artery dissection (CeAD) due to arterial wall weakness (dysplasia) is one of the most common causes of ischemic stroke (IS) at a young age. A rare and little known cause of CeAD is Turner's syndrome (TS)-is an inherited disease caused by completely or partially missing X chromosome. In this paper, we describe 2 female patients, aged 27 and 33 years, with genetically confirmed TS (karyotype 45X0) and internal carotid artery dissection(ICAD).TS frequency among our 304 patients with CeAD was 0.07%. Both patients had short stature, received hormone replacement therapy from the age of 14 and had arterial hypertension. In addition, the first patient suffered from hypothyroidism, osteoporosis and survived a nephrectomy for hydronephrosis. ICAD in first patient manifested by IS. MRI of the neck arteries, MRA and CTA revealed intramural hematoma, hemodynamically significant stenosis, which regressed in 4 months. In the second patient, dissection was manifested by local symptoms (Horner's syndrome, cervicocephalic pain on the dissection side). MRA and CTA revealed a precranial dissected aneurysm of the left ICA (on the side of local symptoms), fusiform expansion of the right ICA, and pathological tortuosity of both ICA. The paper discusses the cause of vasculopathy in TS. It is assumed that connective tissue damage is associated with a deficiency of biglycan - extracellular matrix protein, which interacts with collagen and elastin to strengthen the arterial wall. Biglycan gene is linked to X-chromosome which is completely or partlially missing in TS resulting in a biglycan deficiency. The role of sex hormone deficiency as a cause of arterial wall weakness is unlikely.
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Affiliation(s)
| | | | | | - M V Dreval
- Research Center of Neurology, Moscow, Russia
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17
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Harky A, Sokal PA, Hasan K, Papaleontiou A. The Aortic Pathologies: How Far We Understand It and Its Implications on Thoracic Aortic Surgery. Braz J Cardiovasc Surg 2021; 36:535-549. [PMID: 34617429 PMCID: PMC8522328 DOI: 10.21470/1678-9741-2020-0089] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Thoracic aortic diseases contribute to a major part of cardiac surgeries. The severity of pathologies varies significantly from emergency and life-threatening to conservatively managed conditions. Life-threatening conditions include type A aortic dissection and rupture. Aortic aneurysm is an example of a conservatively managed condition. Pathologies that affect the arterial wall can have a profound impact on the presentation of such cases. Several risk factors have been identified that increase the risk of emergency presentations such as connective tissue disease, hypertension, and vasculitis. The understanding of aortic pathologies is essential to improve management and clinical outcomes.
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Affiliation(s)
- Amer Harky
- Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.,School of Medicine, University of Liverpool, Liverpool, United Kingdom.,Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
| | | | - Khubbaib Hasan
- School of Medicine, University of Liverpool, Liverpool, United Kingdom
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18
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Noordman ID, Fejzic Z, Bos M, Duijnhouwer AL, Weijers G, Kempers M, Merkx R, van der Velden JAEM, Kapusta L. Cardiac abnormalities in girls with Turner syndrome: ECG abnormalities, myocardial strain imaging, and karyotype-phenotype associations. Am J Med Genet A 2021; 185:2399-2408. [PMID: 33969942 PMCID: PMC8359841 DOI: 10.1002/ajmg.a.62259] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/09/2021] [Accepted: 04/24/2021] [Indexed: 12/13/2022]
Abstract
Turner syndrome (TS) is a chromosomal condition which is associated with an increased prevalence of cardiac morbidity and mortality. In this cross‐sectional study, Minnesota‐based electrocardiographic (ECG) abnormalities, aortic dimensions, routine‐ and myocardial strain echocardiographic parameters, and karyotype‐cardiac phenotype associations were assessed in girls with TS. In total, 101 girls with TS (0–18 years) were included. The prevalence of major ECG abnormalities was 2% (T‐wave abnormalities) and 39% had minor ECG abnormalities. Dilatation of the ascending aorta (z‐score > 2) was present in 16%, but the prevalence was much lower when using TS‐specific z‐scores. No left ventricular hypertrophy was detected and the age‐matched global longitudinal strain was reduced in only 6% of the patients. Cardiac abnormalities seemed more common in patients with a non‐mosaic 45,X karyotype compared with other karyotypes, although no statistically significant association was found. Lowering the frequency of echocardiography and ECG screening might be considered in girls with TS without cardiovascular malformations and/or risk factors for aortic dissection. Nevertheless, a large prospective study is needed to confirm our results. The appropriate z‐score for the assessment of aortic dilatation remains an important knowledge gap. The karyotype was not significantly associated with the presence of cardiac abnormalities, therefore cardiac screening should not depend on karyotype alone.
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Affiliation(s)
- Iris D Noordman
- Department of Pediatric Endocrinology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Zina Fejzic
- Department of Pediatric Cardiology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Melanie Bos
- Department of Pediatric Cardiology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | - Gert Weijers
- Medical Imaging, Medical UltraSound Imaging Center, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Marlies Kempers
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Remy Merkx
- Medical Imaging, Medical UltraSound Imaging Center, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Janiëlle A E M van der Velden
- Department of Pediatric Endocrinology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Livia Kapusta
- Department of Pediatric Cardiology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.,Pediatric cardiology unit, Dana-Dwek Children's Hospital, Tel-Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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19
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Sivasubramanian R, Meyers KE. Hypertension in Children and Adolescents with Turner Syndrome (TS), Neurofibromatosis 1 (NF1), and Williams Syndrome (WS). Curr Hypertens Rep 2021; 23:18. [PMID: 33779870 DOI: 10.1007/s11906-021-01136-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/25/2021] [Indexed: 01/15/2023]
Abstract
PURPOSE OF REVIEW Turner syndrome (TS), neurofibromatosis type 1(NF1), and William Syndrome (WS) are 3 genetic conditions that are all associated with a substantial increase in risk of hypertension. In this review, we focus on factors leading to hypertension and on clinical manifestations and management of hypertension in children and adolescents with these genetic conditions RECENT FINDINGS: In most instances, hypertension is secondary. There is a high prevalence of masked hypertension in TS; however, the extent to which control of the BP helps reduce the risk of aortic dissection/aneurysm in TS is not yet fully elucidated. Vasculopathies are the least emphasized but most important manifestation of NF1. Of note, routine screening for pheochromocytoma in NFI is not recommended as it is not cost-effective. Cardiovascular complications are the major cause of death in patients with WBS. ABPM identifies patients without overt aortic or renovascular narrowing. Antihypertensive agents such as ARBs that have direct vascular wall effects and agents that inhibit oxidative stress (minoxidil) should be considered, even in those who do not exhibit overt hypertension. Elevated blood pressure in children and adolescence manifests early with end-organ changes and when left untreated, increases risk for premature onset of cardiovascular disease. Vigilant monitoring of the blood pressure is recommended. Accurate early diagnosis and management of hypertension will delay or prevent target organ damage and ensure a healthier transition to adulthood among children afflicted with these conditions.
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Affiliation(s)
- Ramya Sivasubramanian
- Division of Pediatric Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia, 9th Floor Beurger Building, 3405 Civic Center Boulevard, Philadelphia, PA, 19104, USA
| | - Kevin E Meyers
- Division of Pediatric Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, 9th Floor Beurger Building, 3405 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
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20
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AlSiraj Y, Thatcher SE, Blalock E, Saintilnord WN, Daugherty A, Lu HS, Luo W, Shen YH, LeMaire SA, Arnold AP, Cassis LA. Monosomy X in Female Mice Influences the Regional Formation and Augments the Severity of Angiotensin II-Induced Aortopathies. Arterioscler Thromb Vasc Biol 2021; 41:269-283. [PMID: 33054396 PMCID: PMC8259710 DOI: 10.1161/atvbaha.120.314407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Turner syndrome women (monosomy X) have high risk of aortopathies consistent with a role for sex chromosomes in disease development. We demonstrated that sex chromosomes influence regional development of Ang II (angiotensin II)-induced aortopathies in mice. In this study, we determined if the number of X chromosomes regulates regional development of Ang II-induced aortopathies. Approach and Results: We used females with varying numbers of X chromosomes (XX female mice [XXF] or XO female mice [XOF]) on an C57BL/6J (ascending aortopathies) or low-density lipoprotein receptor deficient (Ldlr-/-) background (descending and abdominal aortopathies) compared with XY males (XYM). To induce aortopathies, mice were infused with Ang II. XOF (C57BL/6J) exhibited larger percent increases in ascending aortic lumen diameters than Ang II-infused XXF or XYM. Ang II-infused XOF (Ldlr-/-) exhibited similar incidences of thoracic (XOF, 50%; XYM, 71%) and abdominal aortopathies (XOF, 83%; XYM, 71%) as XYM, which were greater than XXF (XXF, 0%). Abdominal aortic lumen diameters and maximal external diameters were similar between XOF and XYM but greater than XXF, and these effects persisted with extended Ang II infusions. Larger aortic lumen diameters, abdominal aortopathy incidence (XXF, 20%; XOF, 75%), and maximal aneurysm diameters (XXF, 1.02±0.17; XOF, 1.96±0.32 mm; P=0.027) persisted in ovariectomized Ang II-infused XOF mice. Data from RNA-seq demonstrated that X chromosome genes that escape X-inactivation (histone lysine demethylases Kdm5c and Kdm6a) exhibited lower mRNA abundance in aortas of XOF than XXF (P=0.033 and 0.024, respectively). Conversely, DNA methylation was higher in aortas of XOF than XXF (P=0.038). CONCLUSIONS The absence of a second X chromosome promotes diffuse Ang II-induced aortopathies in females.
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MESH Headings
- Angiotensin II
- Animals
- Aorta, Abdominal/metabolism
- Aorta, Abdominal/pathology
- Aorta, Thoracic/metabolism
- Aorta, Thoracic/pathology
- Aortic Aneurysm, Abdominal/chemically induced
- Aortic Aneurysm, Abdominal/genetics
- Aortic Aneurysm, Abdominal/metabolism
- Aortic Aneurysm, Abdominal/pathology
- Aortic Aneurysm, Thoracic/chemically induced
- Aortic Aneurysm, Thoracic/genetics
- Aortic Aneurysm, Thoracic/metabolism
- Aortic Aneurysm, Thoracic/pathology
- DNA Methylation
- Disease Models, Animal
- Female
- Histone Demethylases/genetics
- Histone Demethylases/metabolism
- Mice, Inbred C57BL
- Mice, Knockout
- Ovariectomy
- Receptors, LDL/deficiency
- Receptors, LDL/genetics
- Severity of Illness Index
- Turner Syndrome/complications
- Turner Syndrome/genetics
- Mice
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Affiliation(s)
- Yasir AlSiraj
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington KY
| | - Sean E. Thatcher
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington KY
| | - Eric Blalock
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington KY
| | - Wesley N. Saintilnord
- Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY
| | - Alan Daugherty
- Department of Physiology, University of Kentucky, Lexington KY
- Saha Cardiovascular Research Center, University of Kentucky, Lexington KY
| | - Hong S. Lu
- Department of Physiology, University of Kentucky, Lexington KY
- Saha Cardiovascular Research Center, University of Kentucky, Lexington KY
| | - Wei Luo
- Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston TX
| | - Ying H. Shen
- Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston TX
| | - Scott A. LeMaire
- Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston TX
| | - Arthur P. Arnold
- Integrative Biology and Physiology, University of California, Los Angeles CA
| | - Lisa A. Cassis
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington KY
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21
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Agasthi P, Pujari SH, Tseng A, Graziano JN, Marcotte F, Majdalany D, Mookadam F, Hagler DJ, Arsanjani R. Management of adults with coarctation of aorta. World J Cardiol 2020; 12:167-191. [PMID: 32547712 PMCID: PMC7284000 DOI: 10.4330/wjc.v12.i5.167] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Revised: 03/21/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Abstract
Coarctation of the aorta (CoA) is a relatively common congenital cardiac defect often causing few symptoms and therefore can be challenging to diagnose. The hallmark finding on physical examination is upper extremity hypertension, and for this reason, CoA should be considered in any young hypertensive patient, justifying measurement of lower extremity blood pressure at least once in these individuals. The presence of a significant pressure gradient between the arms and legs is highly suggestive of the diagnosis. Early diagnosis and treatment are important as long-term data consistently demonstrate that patients with CoA have a reduced life expectancy and increased risk of cardiovascular complications. Surgical repair has traditionally been the mainstay of therapy for correction, although advances in endovascular technology with covered stents or stent grafts permit nonsurgical approaches for the management of older children and adults with native CoA and complications. Persistent hypertension and vascular dysfunction can lead to an increased risk of coronary disease, which, remains the greatest cause of long-term mortality. Thus, blood pressure control and periodic reassessment with transthoracic echocardiography and three-dimensional imaging (computed tomography or cardiac magnetic resonance) for should be performed regularly as cardiovascular complications may occur decades after the intervention.
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Affiliation(s)
- Pradyumna Agasthi
- Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ 85259, United States
| | - Sai Harika Pujari
- Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ 85259, United States
| | - Andrew Tseng
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, United States
| | - Joseph N Graziano
- Division of Cardiology, Phoenix Children's Hospital, Children's Heart Center, Phoenix, AZ 85016, United States
| | - Francois Marcotte
- Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ 85259, United States
| | - David Majdalany
- Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ 85259, United States
| | - Farouk Mookadam
- Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ 85259, United States
| | - Donald J Hagler
- Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, United States
| | - Reza Arsanjani
- Department of Cardiovascular Diseases, Mayo Clinic, Scottsdale, AZ 85259, United States.
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22
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Yang W, Wen D, Chen S, Xue S, Gu J, Dan J, Zheng H. The expression of Nesprin-1 increased in aortic dissection: why? J Thorac Dis 2020; 11:4960-4965. [PMID: 32030211 DOI: 10.21037/jtd.2019.12.32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background To detect the expression of Nesprin-1 in aortic dissection (AD) in patients and to investigate the role of Nesprin-1 in the pathogenesis of AD in a mouse model. Methods Blood and tissue specimens from AD patients were collected. The expression of Nesprin-1 in tissues from AD patients and non-AD patients with heart disease was studied by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the expression and distribution of Nesprin-1 in AD and sham mice were compared in an induced AD mouse model, and detected by immunohistochemistry and qRT-PCR. Results Immunoblotting and qRT-PCR both showed that the expression of Nesprin-1 was significantly higher in AD versus control patients. An animal model of AD was established by continuous injection of Ang II into ApoE-/- mice. The expression of Nesprin-1 in aortic tissue of AD mice was higher than that of sham-operated mice as determined by immunohistochemistry. qRT-PCR showed that Nesprin-1 gene expression in aorta of AD mice was higher than that of sham-operated mice. Conclusions An increased expression of Nesprin-1 was associated with AD, and hence Nesprin-1 may be involved in the pathogenesis of ADs. Preliminary findings suggest that Nesprin-1 may be a therapeutic target for the treatment of AD.
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Affiliation(s)
- Wengang Yang
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Dezhong Wen
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Shaoxi Chen
- Department of Cardiovascular Surgery, Zhe Jiang Hospital, Hangzhou 310030, China
| | - Song Xue
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jianmin Gu
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Jianggui Dan
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Hui Zheng
- Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
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23
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Paulson RJ. Pregnancies in women with Turner Syndrome: how do we counsel our patients? Fertil Steril 2019; 112:219. [DOI: 10.1016/j.fertnstert.2019.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 06/04/2019] [Indexed: 11/25/2022]
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24
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Schäfer M, Browne LP, Truong U, Jaggers JJ, Mitchell MB, Malone L, Morgan G, Chatfield K, McLennan D, Turbendian H, Vargas D, Fonseca B, DiMaria M, Shah A, Ivy MP, Barker AJ, Hunter KS, Wilson N, Ivy DD, Campbell DN. Aortic stiffness in adolescent Turner and Marfan syndrome patients. Eur J Cardiothorac Surg 2019; 54:926-932. [PMID: 29684119 DOI: 10.1093/ejcts/ezy168] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Accepted: 03/25/2018] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES Turner syndrome (TS) and Marfan syndrome (MFS) are partially characterized by aortopathies with a risk of developing severe aortic dilation, stiffness and consequent dissection and aneurysm formation. The incidence of a bicuspid aortic valve (BAV) is also increased in TS. We investigated aortic stiffness in teenage TS and MFS patients and evaluated to what degree stiffness in TS patients is augmented by the presence of a BAV. METHODS Fifty-seven patients with TS (n = 37) and MFS (n = 20), as well as 22 controls with similar age and size distribution underwent evaluation of thoracic aortic stiffness using phase-contrast magnetic resonance imaging. Calculated stiffness indices including pulse wave velocity (PWV), distensibility and relative area change (RAC) were collected to characterize the ascending aorta and descending aorta. PWV was also determined to evaluate global aortic arch stiffness. RESULTS Patients with TS had reduced distensibility (0.43 vs 0.58%/mmHg, P < 0.05) and RAC (21 vs 29%, P < 0.01) in the ascending aorta when compared with normal controls. Similarly, patients with MFS had reduced ascending aortic distensibility (0.39 vs 0.58%/mmHg, P < 0.05) and RAC (22 vs 29%, P < 0.05). There were no differences in measured PWV in the ascending aorta. Patients with TS had significantly elevated PWV measured in the aortic arch when compared with controls (2.7 vs 1.9 m/s, P < 0.05). Patients with MFS had more prominent elevation in aortic arch PWV (4.2 vs 1.9 m/s, P < 0.01). The descending aortas had decreased distensibility (0.36 vs 0.55%/mmHg, P < 0.05) and RAC (18 vs 25%, P < 0.01) only in MFS patients. Additionally, 18 TS patients with a BAV were compared with 19 TS patients with a trileaflet aortic valve, without significant differences observed in any of the considered stiffness indices. CONCLUSIONS TS and MFS teenage patients display evidence of increased aortic stiffness. In TS patients, this is focused in the ascending aorta and is independent of the presence of a BAV. MFS patients display a generalized reduction in compliance of the entire aorta.
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Affiliation(s)
- Michal Schäfer
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Lorna P Browne
- Department of Radiology, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Uyen Truong
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - James J Jaggers
- Division of Congenital Heart Surgery, Department of Surgery, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Max B Mitchell
- Division of Congenital Heart Surgery, Department of Surgery, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Ladonna Malone
- Department of Radiology, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Gareth Morgan
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Kathryn Chatfield
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Daniel McLennan
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Harma Turbendian
- Division of Congenital Heart Surgery, Department of Surgery, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Danial Vargas
- Department of Radiology, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Brian Fonseca
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Michael DiMaria
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Anar Shah
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Margaret P Ivy
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Alex J Barker
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Kendall S Hunter
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Neil Wilson
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - D Dunbar Ivy
- Division of Cardiology, Department of Pediatrics, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - David N Campbell
- Division of Congenital Heart Surgery, Department of Surgery, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
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Krikščiūnienė R, Navickaitė I, Ereminienė E, Lukoševičius S, Žilaitienė B, Verkauskienė R. Relationship between Echocardiographic and Magnetic Resonance-Derived Measurements of the Thoracic Aorta in Turner Syndrome Patients. Int J Endocrinol 2019; 2019:9258726. [PMID: 31531017 PMCID: PMC6721444 DOI: 10.1155/2019/9258726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 07/16/2019] [Indexed: 01/15/2023] Open
Abstract
INTRODUCTION Turner syndrome (TS) is assigned to the rare diseases group. Morbidity and mortality of TS patients are high, particularly due to the cardiovascular disorders, so monitoring for cardiovascular complications must be ensured. The data demonstrate a strong correlation between 2-dimensional echocardiographic (2Decho) evaluation and magnetic resonance imaging (MRI); still, according to recent guidelines, MRI remains a gold standard. In this study, we aimed to compare aortic dimensions on MRI and 2Decho in TS patients. METHODS 50 TS patients (≥18 years) were enrolled into the cross-sectional study. 2Decho and MRI were performed. The measurements of the aorta were assessed in five standard positions on 2Decho and in 9 standard positions on MRI; ASI (aortic size index) of the ascending aorta was calculated since reduced adult height is observed in TS patients. RESULTS ASI on echocardiography strongly correlated with ASI on MRI in all positions of the ascending aorta, but significantly larger medians of ASI were found on 2Decho in all positions of the ascending aorta and arch when compared with MRI measurements. Still, the prevalence of aortic sinus dilation was significantly and more frequently (52% vs. 38%, p < 0.001) observed on MRI when compared with 2Decho. CONCLUSION The relation of aortic size was significant in all positions when comparing the MRI and 2Decho methods; still, the dilatation of the sinus of aorta was more frequently found on MRI compared with echocardiography.
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Affiliation(s)
- Rūta Krikščiūnienė
- Lithuanian University of Health Sciences, Department of Endocrinology, Medical Academy, Kaunas, Lithuania
| | | | - Eglė Ereminienė
- Lithuanian University of Health Sciences, Department of Cardiology, Medical Academy, Kaunas, Lithuania
| | - Saulius Lukoševičius
- Lithuanian University of Health Sciences, Department of Radiology, Medical Academy, Kaunas, Lithuania
| | - Birutė Žilaitienė
- Lithuanian University of Health Sciences, Department of Endocrinology, Medical Academy, Kaunas, Lithuania
| | - Rasa Verkauskienė
- Lithuanian University of Health Sciences, Department of Endocrinology, Medical Academy, Kaunas, Lithuania
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Son SA, Lim KH, Kim GJ. Hybrid Approach of Ruptured Type B Aortic Dissection with an Aberrant Subclavian Artery in a Single Patient with Turner Syndrome: A Case Report. Vasc Specialist Int 2018; 34:121-126. [PMID: 30671422 PMCID: PMC6340697 DOI: 10.5758/vsi.2018.34.4.121] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 11/05/2018] [Accepted: 11/14/2018] [Indexed: 01/15/2023] Open
Abstract
Turner syndrome, also described as 45, X, may present with most serious cardiovascular anomalies including risk of aortic dissection and rupture. In emergency situation, management for aortic dissection with complicated anatomy accompanying vascular anomaly is challenging. Here, we report a rare case of ruptured type B aortic dissection with aberrant subclavian artery and partial anomalous pulmonary venous connection in a Turner syndrome. Through right carotid-subclavian artery bypass and thoracic endovascular aortic repair, successful hybrid endovascular management correlated with a favorable result in this emergency situation.
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Affiliation(s)
- Shin-Ah Son
- Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Kyoung Hoon Lim
- Department of Surgery, Trauma Center, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
| | - Gun-Jik Kim
- Department of Thoracic and Cardiovascular Surgery, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Korea
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Hauck A, Camarda J. Rare Cardiac Emergencies: Aortic Dissection, Pulmonary Hypertensive Crisis, and Pulmonary Embolism. CLINICAL PEDIATRIC EMERGENCY MEDICINE 2018. [DOI: 10.1016/j.cpem.2018.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Aday AW, Kreykes SE, Fanola CL. Vascular Genetics: Presentations, Testing, and Prognostics. CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2018; 20:103. [PMID: 30421267 DOI: 10.1007/s11936-018-0703-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
PURPOSE OF REVIEW Numerous studies have begun to unravel the genetic basis of not only aortic disease but also other forms of commonly encountered vascular diseases. The goal of this review is to provide clinicians a reference to help identify and diagnose different types of vascular disease with a genetic underpinning. RECENT FINDINGS Ongoing studies have identified numerous genes involved in the TGF-β signaling pathway that are also associated with thoracic aortic aneurysm and dissection, and it is possible to test for pathogenic variants in these genes in the clinical setting using commercially available genetic testing panels. Additional studies have begun to identify genetic variants associated with an increased risk of bicuspid aortic valve, abdominal aortic aneurysm, and fibromuscular dysplasia. With increased availability of low-cost genetic testing, clinicians are now able to not only definitively diagnose some vascular syndromes but also provide information on the risk of disease in other family members, as well as provide guidance in terms of family planning. As the cost of genetic testing continues to drop with the benefit of increasing insurance coverage, genetic data will increasingly become part of clinical care for many patients with vascular disease.
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Affiliation(s)
- Aaron W Aday
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, 2525 West End Avenue Suite 300, Nashville, TN, 37203, USA.
| | - Sarah E Kreykes
- Adult Congenital and Cardiovascular Genetics Center, Division of Cardiovascular Medicine, University of Minnesota Medical Center, Minneapolis, MN, USA
| | - Christina L Fanola
- Adult Congenital and Cardiovascular Genetics Center, Division of Cardiovascular Medicine, University of Minnesota Medical Center, Minneapolis, MN, USA
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Joo C, Min JW, Noh G, Seo J. A case report of unexpected sudden cardiac death due to aortic rupture following laparoscopic appendectomy. Medicine (Baltimore) 2018; 97:e12823. [PMID: 30334980 PMCID: PMC6211873 DOI: 10.1097/md.0000000000012823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
INTRODUCTION Aortic dissection is a very rare but life-threatening condition associated with a high mortality. Unexpected sudden cardiac death due to aortic rupture following laparoscopic appendectomy is very rare and may be difficult to diagnose. However, early diagnosis of aortic dissection is essential for the timely treatment and outcome of aortic dissection. CASE PRESENTATION A 50-year-old man underwent a laparoscopic appendectomy. Postoperatively, the patient complained of dyspnea and chest pain. In 25 minutes after arrival in the postanesthesia care unit (PACU), the patient was in asystole. Then, he underwent cardiopulmonary resuscitation (CPR) according to advanced cardiac life support (ACLS) protocol using 1 mg of epinephrine, one 200J DC shock for ventricular fibrillation (V-fib). After that, his noninvasive blood pressure (NIBP) was 80/40 mm Hg, pulse rate (PR) was 140 beats/min, and peripheral oxygen saturation (SpO2) was 84%. His electrocardiogram (ECG) finding was atrial fibrillation (A-fib). After 20 minutes, the patient developed asystole rhythm again and CPR was restarted. He remained severely hypotensive despite vasopressors and died after 5 hours CPR. A forensic autopsy was performed postmoterm and thoracic and abdominal aortic dissection along the root of ascending aorta was present and massive hematoma within right and left thorax was present. CONCLUSION Acute aortic disease can be difficult to recognize; therefore, diagnosis is sometimes delayed or missed. It is important to recognize the atypical symptoms of aortic dissection and maintain a broad differential diagnosis if patients complained of abdominal pain.
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Affiliation(s)
- Chunghee Joo
- Department of Anesthesia and Pain Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon
| | - Joo-Won Min
- Division of Critical Care Medicine, Department of Internal Medicine, Myongji Hospital, Seonam University College of Medicine, Goyang-si
| | - Giyong Noh
- Department of Anesthesia and Pain Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon
| | - Jaeho Seo
- Department of Anesthesia and Pain Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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Donato B, Ferreira MJ. Cardiovascular risk in Turner syndrome. Rev Port Cardiol 2018; 37:607-621. [DOI: 10.1016/j.repc.2017.08.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/12/2017] [Accepted: 08/16/2017] [Indexed: 01/15/2023] Open
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Cardiovascular risk in Turner syndrome. REVISTA PORTUGUESA DE CARDIOLOGIA (ENGLISH EDITION) 2018. [DOI: 10.1016/j.repce.2017.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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Pees C, Heno JA, Häusler G, Ertl DA, Gulesserian T, Michel-Behnke I. Aortic elasticity deterioration proves intrinsic abnormality of the ascending aorta in pediatric Turner syndrome unrelated to the aortic valve morphology. Heart Vessels 2018; 33:1350-1357. [PMID: 29777298 PMCID: PMC6208677 DOI: 10.1007/s00380-018-1187-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 05/11/2018] [Indexed: 01/15/2023]
Abstract
Turner syndrome (TS) is a common genetic disorder in females with high incidence of ascending aortic dilatation and even dissection occurring as early as in the second decade. Known risk factors (RF) are bicuspid aortic valves (BAV), coarctation of the aorta (CoA), and arterial hypertension. Since 10% of dissections occur in patients without RF, an intrinsic aortic wall abnormality has been postulated. This study aimed to investigate the elasticity of the ascending aorta as a surrogate marker of aortic wall texture. Forty-six pediatric patients with genetically proven TS were prospectively examined for the morphology of their aortic valve, and size and elasticity indices of the adjacent aorta. Cohorts of 46 female subjects with tricuspid aortic valves (TAV) and ten non-syndromic females with BAV were investigated as separate control groups. Comparison of healthy controls with TS patients revealed significantly deteriorated elasticity indices in those with TS. Furthermore, normalized aortic dimensions were greater in TS patients, but dilatations of the ascending aorta with z-score levels above two were restricted to those with BAV (14/46). Deteriorated elasticity indices were measured in TS patients, independent of aortic dilatation, BAV, and CoA, and were comparable to those of patients with isolated, non-syndromic BAVs. By measuring elasticity levels as a surrogate for aortic wall texture, we were able to gather evidence that TS presents with an intrinsic abnormality of the ascending aorta even in patients without concomitant BAV, CoA or dilatations as early as in childhood.
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Affiliation(s)
- Christiane Pees
- Pediatric Heart Center Vienna/Division of Pediatric Cardiology, University Children's Hospital Vienna, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
| | - Julian A Heno
- Pediatric Heart Center Vienna/Division of Pediatric Cardiology, University Children's Hospital Vienna, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Gabriele Häusler
- Division of Pediatric Pulmonology, University Children's Hospital Vienna, Vienna, Austria
| | - Diana-Alexandra Ertl
- Division of Pediatric Pulmonology, University Children's Hospital Vienna, Vienna, Austria
| | - Talin Gulesserian
- Pediatric Heart Center Vienna/Division of Pediatric Cardiology, University Children's Hospital Vienna, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Ina Michel-Behnke
- Pediatric Heart Center Vienna/Division of Pediatric Cardiology, University Children's Hospital Vienna, Medical University Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
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Noordman I, Duijnhouwer A, Kapusta L, Kempers M, Roeleveld N, Schokking M, Smeets D, Freriks K, Timmers H, van Alfen-van der Velden J. Phenotype in girls and women with Turner syndrome: Association between dysmorphic features, karyotype and cardio-aortic malformations. Eur J Med Genet 2018; 61:301-306. [PMID: 29339108 DOI: 10.1016/j.ejmg.2018.01.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2017] [Revised: 12/23/2017] [Accepted: 01/01/2018] [Indexed: 01/15/2023]
Abstract
INTRODUCTION Turner syndrome (TS) is a genetic disorder characterized by the (partial) absence or a structural aberration of the second sex chromosome and is associated with a variety of phenotypes with specific physical features and cardio-aortic malformations. The objective of this study was to gain a better insight into the differences in dysmorphic features between girls and women with TS and to explore the association between these features, karyotype and cardio-aortic malformations. METHODS This prospective study investigated 14 dysmorphic features of TS girls and women using a checklist. Three major phenotypic patterns were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype). Patient data including karyotype and cardio-aortic malformations (bicuspid aortic valve (BAV) and aortic coarctation (COA)) were collected. Associations between the prevalence of dysmorphic features, karyotype and cardio-aortic malformations were analysed using chi2-test and odds ratios. RESULTS A total of 202 patients (84 girls and 118 women) were analysed prospectively. Differences in prevalence of dysmorphic features were found between girls and women. A strong association was found between monosomy 45,X and the phenotypic patterns. Furthermore, an association was found between COA and lymphatic phenotype, but no association was found between karyotype and cardio-aortic malformations. CONCLUSION This study uncovered a difference in dysmorphic features between girls and women. Monosomy 45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal phenotype. All patients with TS should be screened for cardio-aortic malformations, because in contrast to previous reports, karyotype and cardio-aortic malformations showed no significant association.
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Affiliation(s)
- Iris Noordman
- Department of Paediatrics, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Anthonie Duijnhouwer
- Department of Cardiology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Livia Kapusta
- Department of Paediatrics, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands; Pediatric Cardiology Unit, Tel-Aviv Sourasky Medical Centre, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Marlies Kempers
- Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Nel Roeleveld
- Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Michiel Schokking
- Department of Paediatrics, Amalia Children's Hospital, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Dominique Smeets
- Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Kim Freriks
- Department of Internal Medicine, Tjongerschans Hospital, Heerenveen, The Netherlands
| | - Henri Timmers
- Department of Internal Medicine, Section of Endocrinology, Radboud University Medical Centre, Nijmegen, The Netherlands
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Obara-Moszynska M, Rajewska-Tabor J, Rozmiarek S, Karmelita-Katulska K, Kociemba A, Rabska-Pietrzak B, Janus M, Siniawski A, Mrozinski B, Graczyk-Szuster A, Niedziela M, Pyda M. The Usefulness of Magnetic Resonance Imaging of the Cardiovascular System in the Diagnostic Work-Up of Patients With Turner Syndrome. Front Endocrinol (Lausanne) 2018; 9:609. [PMID: 30459711 PMCID: PMC6232706 DOI: 10.3389/fendo.2018.00609] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Accepted: 09/25/2018] [Indexed: 01/03/2023] Open
Abstract
Cardiovascular defects occur in 50% of patients with Turner syndrome (TS). The aim of the study was to estimate the usefulness of cardiac magnetic resonance imaging (CMR) and magnetic resonance angiography (angio-MR) as diagnostics in children and adolescents with TS. Forty-one females with TS, aged 13.9 ± 2.2 years, were studied. CMR was performed in 39 patients and angio-MR in 36. Echocardiography was performed in all patients. The most frequent anomalies diagnosed on CMR and angio-MR were as follows: elongation of the ascending aorta (AA) and aortic arch, present in 16 patients (45.7%), a bicuspid aortic valve (BAV), present in 16 patients (41.0%), and partial anomalous pulmonary venous return (PAPVR), present in six patients (17.1%). Aortic dilatation (Z-score > 2) was mostly seen at the sinotubular junction (STJ) (15 patients; 42.8%), the AA (15 patients; 42.8%), the thoracoabdominal aorta at the level of a diaphragm (15 patients; 42.8%), and the transverse segment (14 patients; 40.0%). An aortic size index (ASI) above 2.0 cm/m2 was present in six patients (17.1%) and above 2.5 cm/m2 in three patients (8.6%). The left ventricular end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV) were diminished (Z-score < -2) in 10 (25.6%), 9 (23.1%), and 8 patients (20.5%), respectively. A webbed neck was correlated with the presence of vascular anomalies (p = 0.006). The age and body mass index (BMI) were correlated with the diameter of the aorta. Patients with BAV had a greater aortic diameter at the ascending aorta (AA) segment (p = 0.026) than other patients. ASI was correlated with aortic diameter and descending aortic diameter (AD/DD) ratio (p = 0.002; r = 0.49). There was a significant correlation between the right ventricular (p = 0.002, r = 0.46) and aortic diameters at the STJ segment (p = 0.0047, r = 0.48), as measured by echocardiography and CMR. Magnetic resonance can identify cardiovascular anomalies, dilatation of the aorta, pericardial fluid, and functional impairment of the ventricles not detected by echocardiography. BMI, age, BAV, and elongation of the AA influence aortic dilatation. The ASI and AD/DD ratio are important markers of aortic dilatation. The performed diagnostics did not indicate a negative influence of GH treatment on the cardiovascular system.
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Affiliation(s)
- Monika Obara-Moszynska
- Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland
- *Correspondence: Monika Obara-Moszynska
| | - Justyna Rajewska-Tabor
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Szymon Rozmiarek
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
| | | | - Anna Kociemba
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Barbara Rabska-Pietrzak
- Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Magdalena Janus
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Andrzej Siniawski
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Bartlomiej Mrozinski
- Department of Pediatric Cardiology, Nephrology and Hypertension, Poznan University of Medical Sciences, Poznan, Poland
| | - Agnieszka Graczyk-Szuster
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
| | - Marek Niedziela
- Department of Pediatric Endocrinology and Rheumatology, Poznan University of Medical Sciences, Poznan, Poland
| | - Malgorzata Pyda
- Cardiac Magnetic Resonance Unit, First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland
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Abstract
Genetic aortic syndromes (GAS) include Marfan, Loeys-Dietz, vascular Ehlers-Danlos, and Turner syndrome as well as congenital bicuspid aortic valve. The clinical management of these diseases has certain similarities and differences. We employed medical strategy analysis to test the utility of genetic diagnostics in the management of GAS. We chose the standpoint of the cardiologist for our analysis. In the first step, the medical goals in the management of GAS are specified. In the second step, the accuracy of genetic diagnostics for GAS is examined. Finally, conclusions can be drawn about the utility of genetic diagnostics in managing GAS. We found that genetic diagnostics is necessary to exclude GAS, to diagnose GAS, and to specify disease types. Second, combining phenotype with genotype information maximizes the predictability of the course of disease. Third, with genetic diagnostics it is possible to predict the birth of children with causative mutations for GAS and to initiate drug therapy to prevent the onset of aortic dilatation or to slow down its progression to aortic aneurysm. Finally, genetic diagnostics improves prognostic predictions and thereby contributes to a better timing of elective surgery and to a better choice of procedures. The findings of our medical strategy analysis indicate the high utility of genetic diagnostics for managing GAS.
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36
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Increased aortic stiffness in prepubertal girls with Turner syndrome. J Cardiol 2017; 69:201-207. [DOI: 10.1016/j.jjcc.2016.03.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Revised: 02/24/2016] [Accepted: 03/01/2016] [Indexed: 01/15/2023]
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Eliason JL, Coleman DM, Criado E, Stanley JC. Surgical treatment of abdominal aortic aneurysms in infancy and early childhood. J Vasc Surg 2016; 64:1252-1261. [DOI: 10.1016/j.jvs.2016.04.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 04/14/2016] [Indexed: 10/21/2022]
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Libruder C, Blumenfeld O, Dichtiar R, Laron Z, Zadik Z, Shohat T, Afek A. Mortality and cancer incidence among patients treated with recombinant growth hormone during childhood in Israel. Clin Endocrinol (Oxf) 2016; 85:813-818. [PMID: 27292870 DOI: 10.1111/cen.13131] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Revised: 06/05/2016] [Accepted: 06/08/2016] [Indexed: 01/15/2023]
Abstract
CONTEXT The inconclusive evidence regarding long-term safety of recombinant human growth hormone (rhGH) therapy underlines the need for long-term large-scale cohorts. OBJECTIVE To assess long-term mortality and cancer incidence among patients treated with rhGH during childhood in Israel. DESIGN A population-based cohort study. SETTING Data were retrieved from a national register established in 1988. Mortality data from the national population register were available through 31 December 2014. Data on cancer incidence from the national cancer registry were available through 31 December 2012. PARTICIPANTS All patients ≤19 years approved for rhGH treatment during 1988-2009 were included. Patients were assigned to three risk categories, according to the underlying condition leading to growth disorder. MAIN OUTCOME MEASURES All-cause mortality and cancer incidence rates were calculated, based on person-years at risk. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated, using the Israeli general population as a reference. RESULTS Included were 1687 patients assigned to the low-risk category and 440 patients assigned to the intermediate-risk category. In the low-risk category, all-cause mortality and cancer incidence were not significantly different than expected (SMR 0·81, 95% CI 0·22-2·08 and SIR 0·76, 95% CI 0·09-2·73). In the intermediate-risk category, all-cause mortality and cancer incidence were significantly higher than expected (SMR 4·05, 95% CI 1·62-8·34 and SIR 4·52, 95% CI 1·22-11·57). CONCLUSIONS No increased risk of mortality or cancer incidence was found in low-risk patients treated with rhGH during childhood. Patients with prior risk factors were at higher risk of both mortality and cancer.
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Affiliation(s)
- Carmit Libruder
- Israel Center for Disease Control, Ministry of Health, Petah Tikva, Israel.
| | - Orit Blumenfeld
- Israel Center for Disease Control, Ministry of Health, Petah Tikva, Israel
| | - Rita Dichtiar
- Israel Center for Disease Control, Ministry of Health, Petah Tikva, Israel
| | - Zvi Laron
- Endocrinology and diabetes Research Unit, Schneider Children's Medical Center, Petah Tikva, Israel
| | - Zvi Zadik
- Pediatric Endocrinology Unit, Kaplan Medical Center, Rehovot, Israel
| | - Tamy Shohat
- Israel Center for Disease Control, Ministry of Health, Petah Tikva, Israel
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Arnon Afek
- Israel Ministry of Health, Jerusalem, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Himpel L, Pilarczyk K, Wahbi A, Mourad F, Tsagakis K, Jakob H, Benedik J. Role of regional aortic wall properties in the pathogenesis of thoracic aortic dissection. SCAND CARDIOVASC J 2016; 51:35-39. [DOI: 10.1080/14017431.2016.1210211] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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van den Hoven AT, Duijnhouwer AL, Eicken A, Aboulhosn J, de Bruin C, Backeljauw PF, Demulier L, Chessa M, Uebing A, Veldtman GR, Armstrong AK, van den Bosch AE, Witsenburg M, Roos-Hesselink JW. Adverse outcome of coarctation stenting in patients with Turner syndrome. Catheter Cardiovasc Interv 2016; 89:280-287. [PMID: 27629084 DOI: 10.1002/ccd.26728] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Revised: 07/21/2016] [Accepted: 08/01/2016] [Indexed: 01/15/2023]
Abstract
OBJECTIVES This study examines the outcome and procedural outcomes of percutaneous stent angioplasty for aortic coarctation in patients with Turner syndrome (TS). BACKGROUND TS occurs in 1 in 2,500 live-born females and is associated with aortic coarctation. METHODS In this multicenter, retrospective cohort study, all patients with TS and a coarctation of the aorta, treated with percutaneous stent implantation were included. The procedural strategies were dictated by local protocols. Adverse events at short- and long-term follow-up and qualitative parameters concerning the stent implantation were assessed. RESULTS In the largest study to date of TS patients receiving aortic stents, a total of 19 patients from 10 centers were included. Twelve patients were treated for native and 7 for recurrent coarctation. Age at intervention was 16.9 (7-60) years (median; min-max). The coarctation diameter increased significantly from 8.0 mm (2-12) pre-intervention to 15.0 mm (10-19) post-intervention (P < 0.001). Three (15.8%) adverse events occurred within 30 days of the procedure, including two dissections despite the use of covered stents, one resulting in death. At long-term follow-up (6.5 years, min-max: 1-16), two additional deaths occurred not known to be stent-related. CONCLUSIONS Though percutaneous treatment of aortic coarctation in TS patients is effective, it is associated with serious morbidity and mortality. These risks suggest that alternative treatment options should be carefully weighed against percutaneous stenting strategies. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
| | | | - Andreas Eicken
- Department Pediatric Cardiology and Congenital Heart Disease, German Heart Centre, Munich, Germany
| | - Jamil Aboulhosn
- Ahmanson/UCLA Adult Congenital Heart Disease Center, Ronald Reagan/UCLA Medical Center, Los Angeles, California
| | - Christiaan de Bruin
- Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Philippe F Backeljauw
- Division of Pediatric Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | | | - Massimo Chessa
- Center for Pediatric and Congenital Cardiology, IRCCS Policlinico, San Donato, Italy
| | - Anselm Uebing
- Department Pediatric Cardiology and Congenital Heart Disease, RBHT, London, United Kingdom
| | - Gruschen R Veldtman
- Division of Pediatric Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Aimee K Armstrong
- The Heart Center, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio
| | | | - Maarten Witsenburg
- Department of Congenital Cardiology, Erasmus MC, Rotterdam, The Netherlands
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Elkayam U, Goland S, Pieper PG, Silversides CK. High-Risk Cardiac Disease in Pregnancy. J Am Coll Cardiol 2016; 68:502-516. [DOI: 10.1016/j.jacc.2016.05.050] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Accepted: 05/03/2016] [Indexed: 02/09/2023]
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Somerville S, Rosolowsky E, Suntratonpipat S, Girgis R, Goot BH, Tham EB. Cardiac Magnetic Resonance Imaging in Pediatric Turner Syndrome. J Pediatr 2016; 175:111-115.e1. [PMID: 27233524 DOI: 10.1016/j.jpeds.2016.04.080] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 03/17/2016] [Accepted: 04/22/2016] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To compare the detection of cardiac lesions with the use of cardiac magnetic resonance imaging (CMR) and conventional echocardiography in children with Turner syndrome. STUDY DESIGN Twenty-four girls with Turner syndrome, 8-18 years of age, were recruited through the Pediatric Endocrinology Program. Participants underwent CMR and echocardiography within a 2-year period, and discrepancies between the results of each modality were identified. RESULTS Fifteen of 24 (63%) girls had a cardiac lesion identified on CMR or echocardiography. Both modalities identified the same lesion in 10 of 15 (67%); however, 6 of 15 (40%) participants had a lesion identified on CMR but not echocardiography. Participants with a missed lesion had a trend towards greater body mass index. Aortic dilation and bicuspid aortic valve were the most commonly missed lesions by echocardiography. CONCLUSIONS CMR identifies significant cardiac lesions missed by echocardiography in pediatric patients with Turner syndrome, particularly along the aorta. These findings support the current guidelines that recommend screening CMR in addition to echocardiogram. Early identification of cardiac abnormalities in patients with Turner syndrome will allow for a greater understanding of the natural history in these patients and potentially identify candidates for earlier intervention.
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Affiliation(s)
- Scott Somerville
- Pediatric Endocrinology, University of Alberta, Edmonton, Alberta, Canada
| | | | - Somjate Suntratonpipat
- Pediatric Cardiology, University of Alberta, Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Rose Girgis
- Pediatric Endocrinology, University of Alberta, Edmonton, Alberta, Canada
| | - Benjamin H Goot
- Pediatric Cardiology, University of Alberta, Stollery Children's Hospital, Edmonton, Alberta, Canada
| | - Edythe B Tham
- Pediatric Cardiology, University of Alberta, Stollery Children's Hospital, Edmonton, Alberta, Canada.
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Abstract
Congenital and acquired cardiovascular diseases contribute significantly to the threefold elevated risk of premature death in Turner syndrome. A multitude of cardiovascular anomalies and disorders, many of which deleteriously impact morbidity and mortality, is frequently left undetected and untreated because of poor adherence to screening programmes and complex clinical presentations. Imaging is essential for timely and effective primary and secondary disease prophylaxis that may alleviate the severe impact of cardiovascular disease in Turner syndrome. This review illustrates how cardiovascular disease in Turner syndrome manifests in a complex manner that ranges in severity from incidental findings to potentially fatal anomalies. Recommendations regarding the use of imaging for screening and surveillance of cardiovascular disease in Turner syndrome are made, emphasising the key role of non-invasive and invasive cardiovascular imaging to the management of all patients with Turner syndrome.
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Azamian M, Lalani SR. Cytogenomic Aberrations in Congenital Cardiovascular Malformations. Mol Syndromol 2016; 7:51-61. [PMID: 27385961 DOI: 10.1159/000445788] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Congenital cardiovascular malformations are the most common birth defects, with a complex multifactorial etiology. Genetic factors play an important role, illuminated by numerous cytogenetically visible abnormalities, as well as submicroscopic genomic imbalances affecting critical genomic regions in the affected individuals. Study of rare families with Mendelian forms, as well as emerging next-generation sequencing technologies have uncovered a multitude of genes relevant for human congenital cardiac diseases. It is clear that the complex embryology of human cardiac development, with an orchestrated interplay of transcription factors, chromatin regulators, and signal transduction pathway molecules can be easily perturbed by genomic imbalances affecting dosage-sensitive regions. This review focuses on chromosomal abnormalities contributing to congenital heart diseases and underscores several genomic disorders linked to human cardiac malformations in the last few decades.
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Affiliation(s)
- Mahshid Azamian
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Tex., USA
| | - Seema R Lalani
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Tex., USA
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Affiliation(s)
- Atul Mathur
- Department of Interventional Cardiology, Fortis Escorts Heart Institute, New Delhi, India
| | - Varun Mohan
- Department of Interventional Cardiology, Fortis Escorts Heart Institute, New Delhi, India
| | - Deepak Ameta
- Department of Interventional Cardiology, Fortis Escorts Heart Institute, New Delhi, India
| | - Bhardwaj Gaurav
- Department of Interventional Cardiology, Fortis Escorts Heart Institute, New Delhi, India
| | - Pradeep Haranahalli
- Department of Interventional Cardiology, Fortis Escorts Heart Institute, New Delhi, India
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Di Marco L, Pacini D, Sposito M, Leone A, Pilato E, Loforte A, Lococo V, Di Bartolomeo R. Single-step surgical procedure for total replacement of the thoracic aorta in a case of Turner syndrome. Int J Cardiol 2015; 199:116-8. [PMID: 26188830 DOI: 10.1016/j.ijcard.2015.06.127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 06/26/2015] [Indexed: 12/01/2022]
Affiliation(s)
- Luca Di Marco
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
| | - Davide Pacini
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Mirko Sposito
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Alessandro Leone
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Emanuele Pilato
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Antonino Loforte
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Valeria Lococo
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Roberto Di Bartolomeo
- Department of Cardiac Surgery, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
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Eckhauser A, South ST, Meyers L, Bleyl SB, Botto LD. Turner Syndrome in Girls Presenting with Coarctation of the Aorta. J Pediatr 2015; 167:1062-6. [PMID: 26323199 DOI: 10.1016/j.jpeds.2015.08.002] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 07/06/2015] [Accepted: 08/03/2015] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To evaluate the frequency of Turner syndrome in a population-based, statewide cohort of girls with coarctation of the aorta. STUDY DESIGN The Utah Birth Defects Network was used to ascertain a cohort of girls between 1997 and 2011 with coarctation of the aorta. Livebirths with isolated coarctation of the aorta or transverse arch hypoplasia were included and patients with complex congenital heart disease not usually seen in Turner syndrome were excluded. RESULTS Of 244 girls with coarctation of the aorta, 77 patients were excluded, leaving a cohort of 167 girls; 86 patients (51%) had chromosomal studies and 21 (12.6%) were diagnosed with Turner syndrome. All patients were diagnosed within the first 4 months of life and 5 (24%) were diagnosed prenatally. Fifteen patients (71%) had Turner syndrome-related findings in addition to coarctation of the aorta. Girls with mosaicism were less likely to have Turner syndrome-associated findings (3/6 mosaic girls compared with 12/17 girls with non-mosaic 45,X). Twelve girls (57%) diagnosed with Turner syndrome also had a bicommissural aortic valve. CONCLUSION At least 12.6% of girls born with coarctation of the aorta have karyotype-confirmed Turner syndrome. Such a high frequency, combined with the clinical benefits of an early diagnosis, supports genetic screening for Turner syndrome in girls presenting with coarctation of the aorta.
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Affiliation(s)
- Aaron Eckhauser
- Section of Pediatric Cardiothoracic Surgery, Department of Surgery, University of Utah, Salt Lake City, UT; Heart Center at Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, UT.
| | - Sarah T South
- Department of Pathology, University of Utah, Salt Lake City, UT
| | - Lindsay Meyers
- Heart Center at Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, UT; Division of Pediatric Cardiology, Department of Pediatrics, University of Utah, Salt Lake City, UT
| | - Steven B Bleyl
- Division of Pediatric Cardiology, Department of Pediatrics, University of Utah, Salt Lake City, UT
| | - Lorenzo D Botto
- Division of Medical Genetics, Department of Pediatrics, University of Utah, Salt Lake City, UT
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Attenhofer Jost CH, Greutmann M, Connolly HM, Weber R, Rohrbach M, Oxenius A, Kretschmar O, Luscher TF, Matyas G. Medical treatment of aortic aneurysms in Marfan syndrome and other heritable conditions. Curr Cardiol Rev 2015; 10:161-71. [PMID: 24527681 PMCID: PMC4021286 DOI: 10.2174/1573403x1002140506124902] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2013] [Revised: 12/22/2013] [Accepted: 02/06/2014] [Indexed: 01/15/2023] Open
Abstract
Thoracic aortic
aneurysms can be triggered by genetic disorders such as Marfan syndrome (MFS)
and related aortic diseases as well as by inflammatory disorders such as giant
cell arteritis or atherosclerosis. In all these conditions, cardiovascular risk
factors, such as systemic arterial hypertension, may contribute to faster rate
of aneurysm progression. Optimal medical management to prevent progressive
aortic dilatation and aortic dissection is unknown. β-blockers have been the
mainstay of medical treatment for many years despite limited evidence of
beneficial effects. Recently, losartan, an angiotensin II type I receptor
antagonist (ARB), has shown promising results in a mouse model of MFS and
subsequently in humans with MFS and hence is increasingly used. Several ongoing
trials comparing losartan to β-blockers and/or placebo will better define the
role of ARBs in the near future. In addition, other medications, such as statins
and tetracyclines have demonstrated potential benefit in experimental aortic
aneurysm studies. Given the advances in our understanding of molecular
mechanisms triggering aortic dilatation and dissection, individualized
management tailored to the underlying genetic defect may be on the horizon of
individualized medicine. We anticipate that ongoing research will address the
question whether such genotype/pathogenesis-driven
treatments can replace current phenotype/syndrome-driven strategies and whether
other forms of aortopathies should be treated similarly. In this work, we review
currently used and promising medical treatment options for patients with
heritable aortic aneurysmal disorders.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Gabor Matyas
- Cardiovascular Center Zurich, Klinik Im Park, Seestr. 220, CH-8027 Zurich, Switzerland.
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Abstract
Anatomic aortic anomalies are seen in many medical conditions and are known to cause disturbances in blood flow. Turner syndrome (TS) is a genetic disorder occurring only in females where cardiovascular anomalies, particularly of the aorta, are frequently encountered. In this study, numerical simulations are applied to investigate the flow characteristics in four TS patient- related aortic arches (a normal geometry, dilatation, coarctation and elongation of the transverse aorta). The Quemada viscosity model was applied to account for the non-Newtonian behavior of blood. The blood is treated as a mixture consisting of water and red blood cells (RBC) where the RBCs are modeled as a convected scalar. The results show clear geometry effects where the flow structures and RBC distribution are significantly different between the aortas. Transitional flow is observed as a jet is formed due to a constriction in the descending aorta for the coarctation case. RBC dilution is found to vary between the aortas, influencing the WSS. Moreover, the local variations in RBC volume fraction may induce large viscosity variations, stressing the importance of accounting for the non-Newtonian effects.
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50
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Bills VL, Smithson SF, Tsai-Goodman B, Tometski A, Overton TG. Prenatal diagnosis and postnatal outcome of massive abdominal aortic aneurysms-a case report. Prenat Diagn 2015; 35:923-5. [PMID: 26094847 DOI: 10.1002/pd.4628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Victoria L Bills
- Fetal Medicine Unit, St Michael's Hospital, University Hospitals Bristol NHS Foundation Trust, UK
| | - Sarah F Smithson
- Department of Clinical Genetics, University Hospitals Bristol NHS Foundation Trust, UK
| | - Beverly Tsai-Goodman
- Department of Fetal Cardiology, University Hospitals Bristol NHS Foundation Trust, UK
| | - Andrew Tometski
- Department of Fetal Cardiology, University Hospitals Bristol NHS Foundation Trust, UK
| | - Timothy G Overton
- Fetal Medicine Unit, St Michael's Hospital, University Hospitals Bristol NHS Foundation Trust, UK
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