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Leone DM, Ittleman B, Virk K, Albright C, Arya B, Deen J. Screening for Structural Heart Defects: A Single-Center Retrospective Cost Analysis for Fetal Echocardiography in Adults with Congenital Heart Disease. Pediatr Cardiol 2025:10.1007/s00246-024-03765-6. [PMID: 39812797 DOI: 10.1007/s00246-024-03765-6] [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] [Received: 09/17/2024] [Accepted: 12/29/2024] [Indexed: 01/16/2025]
Abstract
Fetal echocardiography (FE) is recommended for parents with congenital heart disease (pCHD) due to a 3-6% recurrence risk of congenital heart disease (CHD). This study aimed to evaluate the cost of FE for detecting neonatal CHD in pCHD. FE data were collected between 12/2015 and 12/2022. Parents were stratified by CHD complexity: "simple" (class I) and "complex" (class II/III). Cost analysis compared universal FE with selective FE following a positive level II screening anatomical ultrasound (SAU). Primary outcomes included the cost and number needed to screen (NNT) to detect one case of neonatal CHD. Of 419 pCHD cases, 48 were analyzed separately due to additional FE indications. Among the remaining 371 cases (73% maternal, 27% paternal; mean maternal age: 31 years), 14 postnatal CHD cases were detected (3.8%). Recurrence rates were 1.9% for simple pCHD (n = 156) and 5.1% for complex pCHD (n = 215). Universal FE increased the cost of detecting neonatal CHD. The cost per detected case was $267,157 for simple CHD (NNT = 560) and $135,125 for complex CHD (NNT = 288). The lower sensitivity of SAU reduced the cost of universal FE. In this single-center cohort, the recurrence risk of CHD in pCHD is higher than in the general population, particularly in complex cases. Universal screening in simple pCHD is costlier with high-sensitivity SAU. Targeted screening in complex pCHD may offer a better cost-to-risk ratio, highlighting the need for early detection to improve outcomes. The cost effectiveness is dependent on local SAU sensitivity rates.
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Affiliation(s)
- David M Leone
- Heart Institute, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH, USA.
- Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2003, Cincinnati, OH, 45229-3026, USA.
| | | | - Kathryn Virk
- Department of Pediatric Cardiology, Seattle Children's Hospital, Seattle, WA, USA
| | - Catherine Albright
- Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA
| | - Bhawna Arya
- Department of Pediatric Cardiology, Seattle Children's Hospital, Seattle, WA, USA
| | - Jason Deen
- Department of Pediatric Cardiology, Seattle Children's Hospital, Seattle, WA, USA
- Department of Cardiology, University of Washington, Seattle, WA, USA
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2
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Rafique S, Fernandez S, Saleem S, Akram S. Recurrent Systemic Embolization From Bicuspid Aortic Valve Endocarditis in the Setting of Anti-coagulation Use. Cureus 2024; 16:e73187. [PMID: 39651010 PMCID: PMC11624488 DOI: 10.7759/cureus.73187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2024] [Indexed: 12/11/2024] Open
Abstract
Infective endocarditis (IE) is a systemic disease with a high mortality rate even with intravenous antibiotic therapy. Abnormal valves, including bicuspid aortic valves (BAV), are particularly prone to it compared to normal valves. We present a 22-year-old female who was initially admitted for the management of acute splenic infarction when she was diagnosed with a bicuspid aortic valve. With no evidence of a cardiac source of the embolus, she was discharged on anti-coagulation. However, she returned with acute toe ischemia in a few days. She was found to have Streptococcus mitis bacteremia, multiple sub-centimeter aortic valve vegetations on trans-esophageal echocardiogram (TEE), and was subsequently diagnosed with IE. After 3 weeks of IV antibiotics, she presented with thalamic stroke. Our case underscores the challenges in managing IE, particularly in young patients with BAV. Early recognition and aggressive treatment, regardless of vegetation size, and avoidance of anti-coagulation are crucial to mitigate embolic complications.
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Affiliation(s)
- Soomal Rafique
- Internal Medicine, Southern Illinois University School of Medicine, Springfield, USA
| | - Salvador Fernandez
- Infectious Diseases, Southern Illinois University School of Medicine, Springfield, USA
| | - Saliha Saleem
- Infectious Diseases, Southern Illinois University School of Medicine, Springfield, USA
| | - Sami Akram
- Infectious Diseases, Southern Illinois University School of Medicine, Springfield, USA
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3
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Miller D, Martin LJ, Tretter JT, Cnota J, Weaver N, Miller E, Shikany A. Uptake of Screening and Recurrence of Bicuspid Aortic Valve and Thoracic Aortic Aneurysm Among At-Risk Siblings of Pediatric Probands. J Pediatr 2021; 239:219-224. [PMID: 34400210 DOI: 10.1016/j.jpeds.2021.08.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 08/03/2021] [Accepted: 08/09/2021] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To determine uptake of cardiac screening and recurrence of bicuspid aortic valve (BAV) and thoracic aortic aneurysm (TAA) in a population of at-risk siblings of pediatric probands. STUDY DESIGN A retrospective chart review of pediatric patients with known BAV and/or TAA was performed. Echocardiogram data from identified siblings were collected to determine screening uptake and recurrence of BAV and TAA. Statistical analyses were performed using Wilcoxon signed-rank test and chi-square. RESULTS The cohort included 251 probands and 388 at-risk siblings. Among the siblings, 150 had at least 1 echocardiogram, giving an overall screening uptake of 38.7%. The only factor found to be associated with increased uptake was documented recommendation for screening of first-degree relatives in the proband's initial cardiology note (P = .03). A total of 11 screened siblings (7.3%) had BAV and 19 had TAA (12.7%), with an overall combined recurrence of 15.3%. Siblings of probands who had both BAV and TAA had increased recurrence of TAA compared with siblings of probands with isolated BAV (16.1% vs 3.9%, respectively). CONCLUSIONS Given low uptake in at-risk siblings, the opportunity exists to assess barriers for families in pursuing the recommended screening. Furthermore, the relatively high recurrence of BAV and TAA in at-risk siblings highlights the potential for improved health outcomes through increased screening and early detection. Developing standardized guidelines and promoting early cardiac screening in at-risk siblings while counseling families about hereditary risk for BAV and TAA may help improve uptake and optimize clinical management in at-risk pediatric patients.
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Affiliation(s)
- Daniel Miller
- Genetic Counseling Graduate Program, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, OH
| | - Lisa J Martin
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Justin T Tretter
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - James Cnota
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Nicole Weaver
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Erin Miller
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH
| | - Amy Shikany
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
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4
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Marwick TH. Screening of first-degree relatives of patients with bicuspid aortic valve: a counsel of perfection? EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2021; 7:529-531. [PMID: 34477835 DOI: 10.1093/ehjqcco/qcab063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 09/01/2021] [Indexed: 11/13/2022]
Affiliation(s)
- Thomas H Marwick
- Department of Imaging Research, Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, Viv 3004, Australia
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5
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Ison HE, Griffin EL, Parrott A, Shikany AR, Meyers L, Thomas MJ, Syverson E, Demo EM, Fitzgerald KK, Fitzgerald-Butt S, Ziegler KL, Schartman AF, Stone KM, Helm BM. Genetic counseling for congenital heart disease - Practice resource of the national society of genetic counselors. J Genet Couns 2021; 31:9-33. [PMID: 34510635 DOI: 10.1002/jgc4.1498] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 08/02/2021] [Accepted: 08/02/2021] [Indexed: 12/11/2022]
Abstract
Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre- and postnatally.
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Affiliation(s)
- Hannah E Ison
- Stanford Center for Inherited Cardiovascular Disease, Stanford Health Care, Stanford, California, USA
| | - Emily L Griffin
- Department of Pediatrics, Columbia University Medical Center, New York, New York, USA
| | | | - Amy R Shikany
- Cincinnati Children's Hospital Medical Center, The Heart Institute, Cincinnati, Ohio, USA
| | | | - Matthew J Thomas
- Department of Pediatrics, Division of Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA
| | - Erin Syverson
- Department of Pediatrics, Division of Genetics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Erin M Demo
- Sibley Heart Center Cardiology at Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Kristi K Fitzgerald
- Nemours Cardiac Center, Alfred I. DuPont Hospital for Children, Wilmington, Delaware, USA
| | - Sara Fitzgerald-Butt
- Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | - Allison F Schartman
- Department of Obstetrics & Gynecology, Division of Maternal Fetal Medicine, Indiana University Health, Indianapolis, Indiana, USA
| | - Kristyne M Stone
- Department of Obstetrics & Gynecology, Division of Maternal Fetal Medicine, Indiana University Health, Indianapolis, Indiana, USA
| | - Benjamin M Helm
- Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.,Department of Epidemiology, Indiana University Fairbanks School of Public Health, Indianapolis, Indiana, USA
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6
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Abstract
Bicuspid aortic valve (BAV) is the most common valvular congenital heart disease, with a prevalence of 0.5 to 2% in the general population. Patients with BAV are at risk for developing cardiovascular complications, some of which are life-threatening. BAV has a wide spectrum of clinical presentations, ranging from silent malformation to severe and even fatal cardiac events. Despite the significant burden on both the patients and the health systems, data are limited regarding pathophysiology, risk factors, and genetics. Family studies indicate that BAV is highly heritable, with autosomal dominant inheritance, incomplete penetrance, variable expressivity, and male predominance. Owing to its complex genetic model, including high genetic heterogenicity, only a few genes were identified in association with BAV, while the majority of BAV genetics remains obscure. Here, we review the different forms of BAV and the current data regarding its genetics. Given the clear heritably of BAV with the potential high impact on clinical outcome, the clinical value and cost effectiveness of cascade screening are discussed.
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7
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Tessler I, Leshno M, Shmueli A, Shpitzen S, Ronen D, Gilon D. Cost-effectiveness analysis of screening for first-degree relatives of patients with bicuspid aortic valve. EUROPEAN HEART JOURNAL. QUALITY OF CARE & CLINICAL OUTCOMES 2021; 7:447-457. [PMID: 34227670 DOI: 10.1093/ehjqcco/qcab047] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/29/2021] [Accepted: 07/04/2021] [Indexed: 12/25/2022]
Abstract
AIMS Bicuspid aortic valve (BAV) is the commonest congenital heart valve malformation, and is associated with life-threatening complications. Given the high heritability index of BAV, many experts recommend echocardiography screening for first-degree relatives (FDRs) of an index case. Here we aim to evaluate the cost-effectiveness of such cascade screening for BAV. METHODS Using a decision-analytic model, we performed a cost-effectiveness analysis of echocardiographic screening for FDRs of BAV index case. Data on BAV probabilities and complications among FDRs were derived from our institution's BAV familial cohort and from the literature on population-based BAV cohorts with long-term follow-up. Health gain was measured as quality-adjusted life years (QALYs). Cost inputs were based on list prices and literature data. One-way and probabilistic sensitivity analyses were performed to account for uncertainty in the model's variables. RESULTS Screening of FDRs was found to be the dominant strategy, being more effective and less costly than no screening, with savings of €644 and gains of 0.3 QALYs. Results were sensitive throughout the rang of the model's variables, including the full range of reported BAV rates among FDRs across the literature. A gradual decrease of the incremental effect was found with the increase in screening age. CONCLUSIONS This economic evaluation model found that echocardiographic screening of FDRs of BAV index case is not only clinically important but also cost-effective and cost-saving. Sensitivity analysis supported the model's robustness, suggesting its generalization.
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Affiliation(s)
- Idit Tessler
- Braun School of Public Health and Community Medicine, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.,Heart institute, Hadassah Medical Center, Jerusalem, Israel
| | - Moshe Leshno
- Faculty of Management and School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amir Shmueli
- Braun School of Public Health and Community Medicine, Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Shoshana Shpitzen
- Heart institute, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Durst Ronen
- Heart institute, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Dan Gilon
- Heart institute, Hadassah Medical Center, Jerusalem, Israel.,Faculty of Medicine, The Hebrew University, Jerusalem, Israel
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8
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Abstract
Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left‐sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease‐causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL‐associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.
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Affiliation(s)
- Lauren E Parker
- Division of Cardiology Department of Pediatrics Duke University School of Medicine Durham NC
| | - Andrew P Landstrom
- Division of Cardiology Department of Pediatrics Duke University School of Medicine Durham NC.,Department of Cell Biology Duke University School of Medicine Durham NC
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9
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The importance of genetics and genetic counselors in the evaluation of patients with bicuspid aortic valve and aortopathy. Curr Opin Cardiol 2020; 34:73-78. [PMID: 30394908 DOI: 10.1097/hco.0000000000000586] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Bicuspid aortic valve (BAV) is a common congenital heart defect, with an estimated frequency of 1-2% in the general population. BAV may occur as an isolated finding or as a feature of certain syndromes. This article discusses potential genetic causes of BAV, includes a list of current known and candidate genes associated with BAV, provides a hypothetical case demonstrating the importance of genetic testing and cascade screening, and highlights the value of genetic counselors specializing in cardiovascular genetics. RECENT FINDINGS Individuals with BAV are at significantly increased risk of progressive aortic valve disease and aortic root aneurysms. There is high heritability associated with BAV, and several specific genes have recently been associated with BAV. There is wide phenotypic variability among BAV malformations, including which cusps are involved and the degree of aortic root involvement. Genotype-phenotype correlations exist that impact treatment recommendations. Genetic testing can reduce morbidity and mortality by guiding management strategies and identifying asymptomatic relatives before significant complications occur. SUMMARY Identifying cases of BAV with an identifiable genetic cause can significantly impact patients and family members. The list of associated genes is constantly growing. Genetic counselors have an important role in the evaluation of families at risk of BAV.
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10
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Balderston JR, Gertz ZM, Brooks S, Joyce JM, Evans DP. Diagnostic Yield and Accuracy of Bedside Echocardiography in the Emergency Department in Hemodynamically Stable Patients. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:2845-2851. [PMID: 30882920 DOI: 10.1002/jum.14985] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/31/2019] [Accepted: 02/14/2019] [Indexed: 06/09/2023]
Abstract
OBJECTIVES The goal of this study was to determine the diagnostic yield of focused cardiac ultrasound (FOCUS) in hemodynamically stable patients in the emergency department and secondarily to confirm the accuracy of these studies when compared to formal echocardiography. METHODS All hemodynamically stable adult patients who had an emergency physician-performed FOCUS examination completed over a 1-year period were identified using our electronic ultrasound database. Hemodynamic stability was defined as presenting systolic blood pressure higher than 90 mm Hg and not requiring any form of positive pressure ventilation. RESULTS There were 1198 FOCUS examinations performed: 976 in hemodynamically stable patients who were included in our analysis. Twenty-seven percent of patients had new findings, including 154 (16%) new diagnoses of reduced left ventricular function, 105 (11%) new pericardial effusions, and 44 (5%) new diagnoses of RV dilatation. Dyspnea as an indication for the FOCUS examination was the strongest predictor of a positive study. Of patients included, 28% underwent formal echocardiography within 2 days and were analyzed for concordance with regard to left ventricular function and the presence of pericardial effusion. Of 270 studies, 208 were accurate, and 62 were inaccurate, for raw agreement of 77% (κ = 0.53). When stratified by sonographer experience, there was no impact on accuracy. CONCLUSIONS Focused cardiac ultrasound in the emergency department for hemodynamically stable patients revealed new findings in 27% of studies, with a modest correlation with formal echocardiography. In stable patients, FOCUS has the potential for rapid diagnosis of cardiac disease, particularly in patients with dyspnea.
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Affiliation(s)
- Jessica R Balderston
- Department of Emergency Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Zachary M Gertz
- Division of Cardiology, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Sean Brooks
- Department of Emergency Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - J Michael Joyce
- Department of Emergency Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
| | - David P Evans
- Department of Emergency Medicine, Virginia Commonwealth University, Richmond, Virginia, USA
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11
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Borger MA, Fedak PWM, Stephens EH, Gleason TG, Girdauskas E, Ikonomidis JS, Khoynezhad A, Siu SC, Verma S, Hope MD, Cameron DE, Hammer DF, Coselli JS, Moon MR, Sundt TM, Barker AJ, Markl M, Della Corte A, Michelena HI, Elefteriades JA. The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve-related aortopathy: Full online-only version. J Thorac Cardiovasc Surg 2019; 156:e41-e74. [PMID: 30011777 DOI: 10.1016/j.jtcvs.2018.02.115] [Citation(s) in RCA: 179] [Impact Index Per Article: 29.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 01/17/2018] [Accepted: 02/12/2018] [Indexed: 12/11/2022]
Abstract
Bicuspid aortic valve disease is the most common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve-associated aortopathy, but none focused entirely on this disease process. The current guidelines cover all major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research. It is intended to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients.
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Affiliation(s)
- Michael A Borger
- Leipzig Heart Center, Cardiac Surgery, University of Leipzig, Leipzig, Germany.
| | - Paul W M Fedak
- Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | | | - Thomas G Gleason
- Division of Cardiac Surgery, Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pa
| | - Evaldas Girdauskas
- Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany
| | - John S Ikonomidis
- Division of Cardiothoracic Surgery, University of North Carolina, Chapel Hill, NC
| | - Ali Khoynezhad
- Memorial Care Heart and Vascular Institute, Memorial Care Long Beach Medical Center, Long Beach, Calif
| | - Samuel C Siu
- Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Subodh Verma
- Department of Cardiac Surgery, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Michael D Hope
- San Francisco (UCSF) Department of Radiology & Biomedical Imaging, University of California, San Francisco, Calif
| | - Duke E Cameron
- Department of Cardiac Surgery, Massachusetts General Hospital, Boston, Mass
| | - Donald F Hammer
- Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
| | - Joseph S Coselli
- Division of Cardiothoracic Surgery, Texas Heart Institute, Baylor College of Medicine, Houston, Tex
| | - Marc R Moon
- Section of Cardiac Surgery, Washington University School of Medicine, St Louis, Mo
| | - Thoralf M Sundt
- Division of Cardiac Surgery, Massachusetts General Hospital, Boston, Mass
| | - Alex J Barker
- Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Michael Markl
- Departments of Radiology and Biomedical Engineering, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | | | | | - John A Elefteriades
- Department of Cardiothoracic Surgery, Yale University School of Medicine, New Haven, Conn
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12
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The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve-related aortopathy: Executive summary. J Thorac Cardiovasc Surg 2019; 156:473-480. [PMID: 30011756 DOI: 10.1016/j.jtcvs.2017.10.161] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 09/19/2017] [Accepted: 10/16/2017] [Indexed: 12/20/2022]
Abstract
Bicuspid aortic valve disease is a common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve-associated aortopathy, but none focused entirely on this disease process. The current document is an executive summary of "The American Association for Thoracic Surgery Guidelines on Bicuspid Aortic Valve-Related Aortopathy." All major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research are contained within these guidelines. The current executive summary serves as a condensed version of the guidelines to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients.
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13
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Howard C, Picca L, Smith T, Sharif M, Bashir M, Harky A. The bicuspid aortic valve: Is it an immunological disease process? J Card Surg 2019; 34:482-494. [PMID: 31012137 DOI: 10.1111/jocs.14050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 03/26/2019] [Accepted: 04/01/2019] [Indexed: 01/03/2023]
Abstract
Bicuspid aortic valves (BAVs) are the most common congenital cardiac condition and are characterized by a structural abnormality whereby the aortic valve is composed of two leaflets instead of being trileaflet. It is linked to an increased risk for a variety of complications of the aorta, many with an immunological pathogenesis. The aim of this study is to review and analyze the literature regarding immunological processes involving BAVs, associated common pathologies, and their incidence in the population. This study will also examine current trends in surgical and therapeutic approaches to treatment and discuss the future direction of BAV treatment.
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Affiliation(s)
- Callum Howard
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Leonardo Picca
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Tristan Smith
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Monira Sharif
- Department of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital, Dundee, UK
| | - Mohamad Bashir
- Department of Emergency Medicine and Surgery, Macclesfield General Hospital, Macclesfield, UK
| | - Amer Harky
- Department of Cardiothoracic Surgery, Liverpool Heart and Chest, Liverpool, UK
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14
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Shikany AR, Parrott A, James J, Madueme P, Nicole Weaver K, Cassidy C, Khoury PR, Miller EM. Left ventricular outflow tract obstruction: Uptake of familial cardiac screening and parental knowledge from a single tertiary care center. J Genet Couns 2019; 28:779-789. [PMID: 30907979 DOI: 10.1002/jgc4.1117] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 02/20/2019] [Accepted: 02/21/2019] [Indexed: 11/06/2022]
Abstract
Left ventricular outflow tract obstruction (LVOTO) malformations exhibit higher heritability than other cardiac lesions and cardiac screening is encouraged for first-degree relatives. This study sought to determine the uptake of familial cardiac screening in families with an infant with an LVOTO and assess parental knowledge regarding genetics and heritability of LVOTO. A chart review of the period 2010-2015 identified 69 families who received genetic counseling regarding a diagnosis of LVOTO in an infant. Surveys assessing familial cardiac screening and parental knowledge were completed by a parent in 24 families (completion rate of 35%). Forty percent (36/89) of all at-risk first-degree family members completed cardiac screening. The presence of additional congenital malformations in the affected infant was the only significant factor reducing the uptake of familial cardiac screening (p = 0.003). The reported uptake of screening for subsequent at-risk pregnancies was 11/12 (92%) compared to 25/77 (32%) of living at-risk relatives. Survey respondents answered seven knowledge questions with an average score of 5.2 and all correctly identified that LVOTO can run in families. Uptake of familial cardiac screening is occurring in less than half of at-risk individuals, despite parents demonstrating basic knowledge and receiving genetic counseling. Follow-up counseling in the outpatient setting to review familial screening recommendations should be considered to increase uptake and optimize outcomes.
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Affiliation(s)
- Amy R Shikany
- Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Ashley Parrott
- Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Jeanne James
- Division of Cardiology, Children's Hospital of Wisconsin, Milwaukee, Wisconsin
| | - Peace Madueme
- Nemours Cardiac Center, Nemours Children's Hospital, Orlando, Florida
| | - Kathryn Nicole Weaver
- Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Christine Cassidy
- Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Philip R Khoury
- Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Erin M Miller
- Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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15
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Abstract
A bicuspid aortic valve is not only a common congenital heart defect but also an enigmatic condition that can cause a large spectrum of diseases, such as aortic valve stenosis and severe heart failure in newborns whereas aortic dissection in adults. On the contrary, a bicuspid aortic valve can also occur with normal function throughout life and never need treatment. Numerous genetic mechanisms are involved in the abnormal cellular functions that may cause abnormal development of the aortic valve during early foetal life. As several chromosomal disorders are also associated with a bicuspid valve, there does not appear to be an apparent common trigger to the abnormal development of the aortic valve. The clinical care of the bicuspid aortic valve patient has been changed by a significant body of evidence that has improved the understanding of the natural history of the disease, including when to best intervene with valve replacement and when to provide prophylactic aortic root surgery. Moreover, as bicuspid valve disease is also part of various syndromes, we can identify high-risk patients in whom a bicuspid valve is much more unfavourable than in the normal population. This review provides an overview of all aspects of the bicuspid aortic valve condition and gives an updated perspective on issues from pathophysiology to clinical care of bicuspid aortic valve disease and associated aortic disease in asymptomatic, symptomatic, and pregnant patients, as well as our viewpoint on population screening.
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Familial Screening for Left-Sided Congenital Heart Disease: What Is the Evidence? What Is the Cost? Diseases 2017; 5:diseases5040029. [PMID: 29292713 PMCID: PMC5750540 DOI: 10.3390/diseases5040029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 12/03/2017] [Accepted: 12/05/2017] [Indexed: 11/21/2022] Open
Abstract
Since the American Heart Association’s recommendation for familial screening of adults with congenital heart disease for bicuspid aortic valve, similar recommendations for other left-sided heart defects, such as hypoplastic left heart syndrome (HLHS), have been proposed. However, defining at-risk populations for these heart defects based on genetics is less straightforward due to the wide variability of inheritance patterns and non-genetic influences such as environmental and lifestyle factors. We discuss whether there is sufficient evidence to standardize echocardiographic screening for first-degree relatives of children diagnosed with HLHS. Due to variations in the inclusion of cardiac anomalies linked to HLHS and the identification of asymptomatic individuals with cardiac malformations, published studies are open to interpretation. We conclude that familial aggregation of obstructive left-sided congenital heart lesions in families with history of HLHS is not supported and recommend that additional screening should adopt a more conservative definition of what truly constitutes this heart defect. More thorough consideration is needed before embracing familial screening recommendations of families of patients with HLHS, since this could inflict serious costs on healthcare infrastructure and further burden affected families both emotionally and financially.
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Abnormal Longitudinal Growth of the Aorta in Children with Familial Bicuspid Aortic Valve. Pediatr Cardiol 2017; 38:1709-1715. [PMID: 28948327 PMCID: PMC5798863 DOI: 10.1007/s00246-017-1740-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Accepted: 09/15/2017] [Indexed: 12/31/2022]
Abstract
Bicuspid aortic valve (BAV) is the most common type of congenital heart defect (CHD) and is associated with clinically significant cardiovascular complications including valve calcification and ascending aortopathy (AscAo), predominantly occurring in adulthood. While a limited number of genetic etiologies for BAV have been defined, family members of affected individuals display BAV along with other left-sided CHD. This has led to guidelines from the American Heart Association and American College of Cardiology that recommend echocardiographic screening of first-degree relatives of affected adults. While potentially beneficial in adults, the yield of such screening in children is unknown. The purpose of this study was to investigate a cohort of children with familial BAV to determine the frequency of development of AscAo, and to identify risk factors that contribute to abnormal aortic growth. Echocardiograms over a 10-year follow-up period were reviewed on 26 patients with familial BAV [22 male, 4 female; 22 with isolated BAV, 6 with BAV and aortic coarctation (CoA)]. All had a family history of CHD and were recruited from 2005 to 2010 as part of a genetics research study. Four aortic segments (annulus, root, sinotubular junction, ascending aorta) on parasternal long-axis echocardiographic images were measured by a single observer. The mean age at first echocardiogram was 7.1 ± 5.5 and that was 13.8 ± 6.2 years at the last echocardiogram. Only patients with > 2 echocardiograms in the 10-year period were included. Z score measurements of the aorta were plotted over time and based on these the cohort was divided into two groups: Group 1 (abnormal)-Z score for any segment > 2 or a change in Z score > 2 over follow-up; Group 2 (normal)-Z score < 2 throughout follow-up and change in Z score < 2. Nineteen out of 26 children displayed abnormal aortic growth or dilation of the aorta. BAV with right/left cusp fusion was more frequent in Group 1 (15/18) versus Group 2 (3/7) (p < 0.05). There were no significant differences in gender, aortic valve dysfunction, presence of CoA, family history, cardiac function, presence of left ventricular hypertrophy, or medication use between the 2 groups. In our longitudinal study of children with familial BAV, the majority display evidence of abnormal growth of the ascending aorta during the follow-up period consistent with AscAo and support the extension of current adult guidelines to the pediatric population. While we find that right/left cusp fusion is a risk factor for abnormal aortic growth, additional studies are needed to identify other factors to better select children who require serial screening.
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19
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Freeze SL, Landis BJ, Ware SM, Helm BM. Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling. J Genet Couns 2016; 25:1171-1178. [PMID: 27550231 DOI: 10.1007/s10897-016-0002-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 07/31/2016] [Indexed: 12/16/2022]
Abstract
Bicuspid aortic valve (BAV) is the most common congenital heart defect and falls in the spectrum of left-sided heart defects, also known as left ventricular outflow tract obstructive (LVOTO) defects. BAV is often identified in otherwise healthy, asymptomatic individuals, but it is associated with serious long term health risks including progressive aortic valve disease (stenosis or regurgitation) and thoracic aortic aneurysm and dissection. BAV and other LVOTO defects have high heritability. Although recommendations for cardiac screening of BAV in at-risk relatives exist, there are no standard guidelines for providing genetic counseling to patients and families with BAV. This review describes current knowledge of BAV and associated aortopathy and provides guidance to genetic counselors involved in the care of patients and families with these malformations. The heritability of BAV and recommendations for screening are highlighted. While this review focuses specifically on BAV, the principles are applicable to counseling needs for other LVOTO defects.
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Affiliation(s)
- Samantha L Freeze
- Department of Pediatrics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Benjamin J Landis
- Department of Pediatrics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Medical & Molecular Genetics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, 975 West Walnut Street, IB-130, Indianapolis, IN, 46202, USA
| | - Stephanie M Ware
- Department of Pediatrics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA
- Department of Medical & Molecular Genetics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, 975 West Walnut Street, IB-130, Indianapolis, IN, 46202, USA
| | - Benjamin M Helm
- Department of Medical & Molecular Genetics, Riley Hospital for Children at IU Health, Indiana University School of Medicine, 975 West Walnut Street, IB-130, Indianapolis, IN, 46202, USA.
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Chaix MA, Andelfinger G, Khairy P. Genetic testing in congenital heart disease: A clinical approach. World J Cardiol 2016; 8:180-191. [PMID: 26981213 PMCID: PMC4766268 DOI: 10.4330/wjc.v8.i2.180] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 10/16/2015] [Accepted: 12/11/2015] [Indexed: 02/06/2023] Open
Abstract
Congenital heart disease (CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient follow-up. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.
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Kelle AM, Qureshi MY, Olson TM, Eidem BW, O'Leary PW. Familial Incidence of Cardiovascular Malformations in Hypoplastic Left Heart Syndrome. Am J Cardiol 2015; 116:1762-6. [PMID: 26433269 DOI: 10.1016/j.amjcard.2015.08.045] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Revised: 08/29/2015] [Accepted: 08/29/2015] [Indexed: 10/23/2022]
Abstract
Obstructive left-sided congenital heart lesions exhibit familial clustering, and familial echocardiographic screening for bicuspid aortic valve has become standard practice. Hypoplastic left heart syndrome (HLHS) is a severe left-sided obstructive lesion; however, familial screening is not universally recommended. The purpose of this study was to define the incidence of cardiovascular malformations (CVMs) in first-degree relatives of HLHS probands. First-degree relatives were screened for CVM by transthoracic echocardiography. Screening was completed in 152 family members (97 parents and 55 siblings) of 52 probands. Of these, 17 of 152 (11%) had CVM. Anomalies detected included: bicuspid aortic valve in 5 (3%), isolated dilated ascending aorta in 4 (3%), coarctation of the aorta in 1, partial anomalous pulmonary venous connection in 1, anomalous, intramural coronary artery in 1, bicuspid pulmonary valve in 1, and other anomalies in 4. Most were previously undiagnosed (11 of 17, 65%). Fourteen of 52 families (27%) had ≥1 relative with CVM. Overall, 7 of 55 siblings (13%), 5 of 46 fathers (11%) and 5 of 51 mothers (10%) had CVM. Although the incidence of CVM in first-degree relatives of HLHS probands was lower in this cohort than previously reported, it remained substantial, with at least one additional member having CVM in 27% of families. The frequent occurrence of undiagnosed CVM highlights the importance of routine familial screening in HLHS. In fact, even if screening was done in childhood, it may be appropriate to screen again in the third or fourth decade to exclude isolated enlargement of the ascending aorta.
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Andelfinger G, Loeys B, Dietz H. A Decade of Discovery in the Genetic Understanding of Thoracic Aortic Disease. Can J Cardiol 2015; 32:13-25. [PMID: 26724507 DOI: 10.1016/j.cjca.2015.10.017] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 10/14/2015] [Accepted: 10/18/2015] [Indexed: 12/23/2022] Open
Abstract
Aortic aneurysms are responsible for a significant number of all deaths in Western countries. In this review we provide a perspective on the important progress made over the past decade in the understanding of the genetics of this condition, with an emphasis on the more frequent forms of vascular smooth muscle and transforming growth factor β (TGF-β) signalling alterations. For several nonsyndromic and syndromic forms of thoracic aortic disease, a genetic basis has now been identified, with 3 main pathomechanisms that have emerged: perturbation of the TGF-β signalling pathway, disruption of the vascular smooth muscle cell (VSMC) contractile apparatus, and impairment of extracellular matrix synthesis. Because smooth muscle cells and proteins of the extracellular matrix directly regulate TGF-β signalling, this latter pathway emerges as a key component of thoracic aortic disease initiation and progression. These discoveries have revolutionized our understanding of thoracic aortic disease and provided inroads toward gene-specific stratification of treatment. Last, we outline how these genetic findings are translated into novel pharmaceutical approaches for thoracic aortic disease.
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Affiliation(s)
- Gregor Andelfinger
- Cardiovascular Genetics, Department of Pediatrics, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
| | - Bart Loeys
- Centre for Medical Genetics, University Hospital of Antwerp/University of Antwerp, Antwerp, Belgium; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Hal Dietz
- Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Division of Pediatric Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Kim HS, Jeong K, Cho HJ, Choi WY, Choi YE, Ma JS, Cho YK. Total anomalous pulmonary venous return in siblings. J Cardiovasc Ultrasound 2014; 22:213-9. [PMID: 25580197 PMCID: PMC4286644 DOI: 10.4250/jcu.2014.22.4.213] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2014] [Revised: 08/12/2014] [Accepted: 11/27/2014] [Indexed: 12/03/2022] Open
Abstract
Total anomalous pulmonary venous return (TAPVR) is a rare and critical congenital vascular anomaly that requires an early operation. However, initial symptoms of TAPVR may be non-specific, and cardiovascular findings may be minimal. The heart may not be enlarged and there is often no cardiac murmur. Without cardiac murmur, these symptoms are similar to those of respiratory distress syndrome in newborns. Therefore, a high degree of suspicion and an early diagnosis of TAPVR are important. This condition generally occurs without a family history and has a low recurrence rate, but several familial cases, including siblings, have been reported worldwide. Additionally, several chromosomal or gene abnormalities associated with TAPVR have been reported. In the case presented here, two brothers with a 6-year age gap were diagnosed with TAPVR. Surgery was performed without cardiac or neurological complications. This is the first report on TAPVR in siblings in Korea.
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Affiliation(s)
- Ho-Sung Kim
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Kumi Jeong
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Hwa-Jin Cho
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Woo-Yeon Choi
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Young Earl Choi
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Jae Sook Ma
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
| | - Young Kuk Cho
- Department of Pediatrics, Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea
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