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Schirm N, Böhm L, Zimmermann T, Meyer N, von Versen-Höynck F. Family planning after transplantation: sex- and organ-related differences in the perception of medical counseling and social challenges. Arch Gynecol Obstet 2025; 311:275-322. [PMID: 39470769 PMCID: PMC11890408 DOI: 10.1007/s00404-024-07703-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Accepted: 08/17/2024] [Indexed: 11/01/2024]
Abstract
PURPOSE Transplant patients are increasingly of childbearing age. Organ-related health as well as pregnancy-related risks require a standardized approach to family planning counseling. The aim of this study was to explore sex- and organ-related counseling differences and expectations in family planning to improve counseling services and reduce risks after transplantation. METHODS The study was designed as a cross-sectional, multi-center cohort study. A total of 251 participants aged between 18 and 45 years with a visceral or thoracic transplant completed a questionnaire on their attitude toward family planning and experience with medical consultation. RESULTS More female than male participants had a desire to have children. Males believed their transplantation-related medication had an influence on their fertility, while women worried it could harm their child. Contraceptive counseling was negated by 43.6% of the women and 73.4% of the men. Medical advice regarding family planning was highly requested by both sexes. Women felt more influenced in their family planning than men. Female thoracic organ recipients worried about a pregnancy more than visceral organ recipients. Women showed great awareness for pregnancy-related risks with the majority wanting to plan a pregnancy beforehand. CONCLUSION The findings revealed a lack of contraceptive counseling and a lack of family planning advice by physicians.
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Affiliation(s)
- Nina Schirm
- Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Lea Böhm
- Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Tanja Zimmermann
- Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Nadia Meyer
- Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany
| | - Frauke von Versen-Höynck
- Department of Obstetrics and Gynecology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
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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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Fernandez-Campos BA, Grewal J, Kiess M, Siu SC, Pfaller B, Sermer M, Mason J, Silversides CK, Haberer K. Adverse fetal/neonatal and obstetric outcomes in pregnancies with both maternal and fetal heart disease. J Perinatol 2024; 44:1424-1431. [PMID: 39043994 PMCID: PMC11442303 DOI: 10.1038/s41372-024-02058-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 06/16/2024] [Accepted: 07/09/2024] [Indexed: 07/25/2024]
Abstract
OBJECTIVE To investigate fetal/neonatal and obstetric events in pregnancies with both maternal and fetal heart disease. STUDY DESIGN From the CARPREG database, singleton pregnancies (>24 weeks) in patients with structural heart disease that underwent fetal/neonatal echocardiograms were selected and separated in two groups: maternal heart disease only (M-HD) and maternal and fetal heart disease (MF-HD). Differences in adverse fetal/neonatal (death, preterm birth, and small for gestational age) and obstetric (preeclampsia/eclampsia) outcomes between groups were analyzed. RESULTS From 1011 pregnancies, 93 had MF-HD. Fetal/neonatal events (38.7% vs 25.3%, p = 0.006) and spontaneous preterm birth (10.8% vs 4.9%, p = 0.021) were more frequent in MF-HD compared to M-HD, with no difference in obstetric events. MF-HD remained as a significant predictor of fetal/neonatal events after adjustment (OR:1.883; 95% CI:1.182-3.000; p = 0.008). CONCLUSIONS Pregnancies with MF-HD are at risk of adverse fetal/neonatal events and spontaneous preterm birth. Larger studies are needed to determine their association with preeclampsia.
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Affiliation(s)
- Beatriz A Fernandez-Campos
- Division of Cardiology, University of Toronto, Pregnancy and Heart Disease Program, Mount Sinai and Toronto General Hospitals, Toronto, ON, Canada
| | - Jasmine Grewal
- Division of Cardiology, St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Marla Kiess
- Division of Cardiology, St Paul's Hospital, University of British Columbia, Vancouver, BC, Canada
| | - Samuel C Siu
- Division of Cardiology, University of Toronto, Pregnancy and Heart Disease Program, Mount Sinai and Toronto General Hospitals, Toronto, ON, Canada
- Division of Cardiology, University of Western Ontario, London, ON, Canada
| | - Birgit Pfaller
- Department of Internal Medicine 1, University Hospital of St. Pölten, Karl Landsteiner University of Health Sciences, Karl Landsteiner Institute for Nephrology, St. Pölten, Austria
| | - Mathew Sermer
- Division of Maternal Fetal Medicine, University of Toronto, Special Pregnancy Program, Mount Sinai Hospital, Toronto, ON, Canada
| | - Jennifer Mason
- Division of Maternal Fetal Medicine, University of Toronto, Special Pregnancy Program, Mount Sinai Hospital, Toronto, ON, Canada
| | - Candice K Silversides
- Division of Cardiology, University of Toronto, Pregnancy and Heart Disease Program, Mount Sinai and Toronto General Hospitals, Toronto, ON, Canada
| | - Kim Haberer
- Division of Pediatric Cardiology, Cohen Children's Medical Center of New York- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA.
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Nawaz K, Alifah N, Hussain T, Hameed H, Ali H, Hamayun S, Mir A, Wahab A, Naeem M, Zakria M, Pakki E, Hasan N. From genes to therapy: A comprehensive exploration of congenital heart disease through the lens of genetics and emerging technologies. Curr Probl Cardiol 2024; 49:102726. [PMID: 38944223 DOI: 10.1016/j.cpcardiol.2024.102726] [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: 06/20/2024] [Accepted: 06/26/2024] [Indexed: 07/01/2024]
Abstract
Congenital heart disease (CHD) affects approximately 1 % of live births worldwide, making it the most common congenital anomaly in newborns. Recent advancements in genetics and genomics have significantly deepened our understanding of the genetics of CHDs. While the majority of CHD etiology remains unclear, evidence consistently indicates that genetics play a significant role in its development. CHD etiology holds promise for enhancing diagnosis and developing novel therapies to improve patient outcomes. In this review, we explore the contributions of both monogenic and polygenic factors of CHDs and highlight the transformative impact of emerging technologies on these fields. We also summarized the state-of-the-art techniques, including targeted next-generation sequencing (NGS), whole genome and whole exome sequencing (WGS, WES), single-cell RNA sequencing (scRNA-seq), human induced pluripotent stem cells (hiPSCs) and others, that have revolutionized our understanding of cardiovascular disease genetics both from diagnosis perspective and from disease mechanism perspective in children and young adults. These molecular diagnostic techniques have identified new genes and chromosomal regions involved in syndromic and non-syndromic CHD, enabling a more defined explanation of the underlying pathogenetic mechanisms. As our knowledge and technologies continue to evolve, they promise to enhance clinical outcomes and reduce the CHD burden worldwide.
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Affiliation(s)
- Khalid Nawaz
- Department of Medical Laboratory Technology, Khyber Medical University, Peshawar, 25100, Khyber Pakhtunkhwa, Pakistan
| | - Nur Alifah
- Faculty of Pharmacy, Universitas Hasanuddin, Jl. Perintis Kemerdekaan Km 10, Makassar, 90245, Republic of Indonesia
| | - Talib Hussain
- Women Dental College, Khyber Medical University, Abbottabad, 22080, Khyber Pakhtunkhwa, Pakistan
| | - Hamza Hameed
- Department of Cardiology, Pakistan Institute of Medical Sciences (PIMS), Islamabad, 04485, Punjab, Pakistan
| | - Haider Ali
- Department of Pharmacy, Kohat University of Science and Technology, Kohat, 26000, Khyber Pakhtunkhwa, Pakistan
| | - Shah Hamayun
- Department of Cardiology, Pakistan Institute of Medical Sciences (PIMS), Islamabad, 04485, Punjab, Pakistan
| | - Awal Mir
- Department of Medical Laboratory Technology, Khyber Medical University, Peshawar, 25100, Khyber Pakhtunkhwa, Pakistan
| | - Abdul Wahab
- Department of Pharmacy, Kohat University of Science and Technology, Kohat, 26000, Khyber Pakhtunkhwa, Pakistan
| | - Muhammad Naeem
- Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Punjab, Pakistan
| | - Mohammad Zakria
- Advanced Center for Genomic Technologies, Khyber Medical University, Peshawar, 25100, Khyber Pakhtunkhwa, Pakistan
| | - Ermina Pakki
- Faculty of Pharmacy, Universitas Hasanuddin, Jl. Perintis Kemerdekaan Km 10, Makassar, 90245, Republic of Indonesia
| | - Nurhasni Hasan
- Faculty of Pharmacy, Universitas Hasanuddin, Jl. Perintis Kemerdekaan Km 10, Makassar, 90245, Republic of Indonesia.
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Rahnama N, Jemâa NB, Colson A, Pasquet A, de Castro LH, Debiève F, Pierard S. Pregnancy in women with congenital heart disease: New insights into neonatal risk prediction. Am Heart J 2024; 273:148-158. [PMID: 38679190 DOI: 10.1016/j.ahj.2024.04.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 04/16/2024] [Accepted: 04/16/2024] [Indexed: 05/01/2024]
Abstract
BACKGROUND Advances in managing adult congenital heart disease (ACHD) have led to an increased number of women with CHD reaching childbearing age. This demographic shift underscores the need for improved understanding and prediction of complications during pregnancy in this specific ACHD population. Despite progress in maternal cardiac risk assessment, the prediction of neonatal outcomes for ACHD pregnancies remains underdeveloped. Therefore, the aims of this study are to assess neonatal outcomes in a CHD women population, to identify their predictive factors and to propose a new risk score for predicting neonatal complications. METHODS This registry study included all women born between 1975 and 1996 diagnosed with ACHD who underwent at least one cardiology consultation for ACHD in Cliniques Universitaires Saint-Luc. A multivariate analysis was performed to identify predictors of neonatal complications and these were incorporated into a new risk index. Its validity was assessed using bootstrap method. This score was then compared with scores adapted from the ZAHARA and CARPREG studies for offspring events prediction. RESULTS Analysis of 491 pregnancies revealed 31.4% of neonatal complications. Four significant predictors of adverse neonatal outcomes were identified: cardiac treatment during pregnancy (OR 14.8, 95%CI [3.4-66]), hypertensive disorders of pregnancy (OR 11.4, 95%CI [3.4-39.0]), smoking during pregnancy (OR 10.6, 95%CI [2.8-40.6]), and pre-pregnancy BMI <18.5 kg/m² (OR 6.5, 95%CI [2.5-16.5]). The risk model demonstrated an AUC of 0.70 (95%CI [0.65-0.75]), which remained stable after bootstrap validation. This model significantly outperformed the scores adapted from ZAHARA and CARPREG data. Based on the regression coefficients, a risk score was subsequently developed comprising five risk categories. CONCLUSIONS One third of ACHD pregnancies are complicated by poor neonatal outcome. These complications are determined by four independent factors relating to the cardiac and non-cardiac status of the patients, which have been incorporated into a risk score. Our study is one of the first to propose a predictive risk score of neonatal outcomes in ACHD pregancies, and paves the way for other validation and confirmation studies.
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Affiliation(s)
- Nour Rahnama
- Cardiovascular Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Nour Ben Jemâa
- Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Arthur Colson
- Obstetrics Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Physiopathologie de la Reproduction (REPR), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Agnès Pasquet
- Cardiovascular Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | | | - Frédéric Debiève
- Obstetrics Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Physiopathologie de la Reproduction (REPR), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium
| | - Sophie Pierard
- Cardiovascular Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium; Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain (UCLouvain), Brussels, Belgium.
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Calcara S, Paeltz A, Richards B, Sisk T, Stiver C, Ogunleye O, Texter K, Mah ML, Cua CL. The Utility of Screening Fetal Echocardiograms Following Normal Level II Ultrasounds in Fetuses with Maternal Congenital Heart Disease. Cardiol Ther 2024; 13:163-171. [PMID: 38261162 PMCID: PMC10899149 DOI: 10.1007/s40119-024-00350-z] [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: 11/15/2023] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
INTRODUCTION Fetal echocardiograms (F-echo) are recommended in all pregnancies when maternal congenital heart disease (CHD) is present, even if there was a prior level II ultrasound (LII-US) that was normal. The goal of this study was to evaluate if any diagnosis of a critical CHD was missed in a fetus with maternal CHD who had a normal LII-US. METHODS A retrospective chart review of all F-echoes where the indication was maternal CHD between 1/1/2015 to 12/31/2022 was performed. Fetuses were included if they had a LII-US that was read as normal and had an F-echo. Critical CHD was defined as CHD requiring catheterization or surgical intervention < 1 month of age. RESULTS A total of 296 F-echoes on fetuses with maternal CHD were evaluated, of which 175 met inclusion criteria. LII-US was performed at 19.8 ± 2.9 weeks gestational age and F-echo was performed at 24.2 ± 2.8 weeks gestational age. No patient with a normal LII-US had a diagnosis of a critical CHD by F-echo (negative predictive value = 100%). Evaluating those patients that had a negative LII-US, ten patients were diagnosed with non-critical CHD postnatally (negative predictive value = 94.3%). F-echo correctly diagnosed two of the ten missed LII-US CHD. CONCLUSIONS Critical CHD was not missed with a normal LII-US in this at risk population. F-echo also missed the majority of CHD when a LII-US was read as normal. A cost-benefit analysis of screening F-echo in fetuses with maternal CHD should be conducted if a normal LII-US has been performed.
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Affiliation(s)
- Sophia Calcara
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Amanda Paeltz
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | | | - Tracey Sisk
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Corey Stiver
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Oluseyi Ogunleye
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Karen Texter
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - May Ling Mah
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA
| | - Clifford L Cua
- Heart Center, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
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van der Zande JA, Tutarel O, Ramlakhan KP, van der Bosch AE, Bordese R, Zengin E, Wagner WE, de Sousa L, Clifford P, Johnson MR, Hall R, Roos-Hesselink JW. Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry of Pregnancy And Cardiac disease (ROPAC). Open Heart 2023; 10:e002406. [PMID: 37550057 PMCID: PMC10407418 DOI: 10.1136/openhrt-2023-002406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 07/22/2023] [Indexed: 08/09/2023] Open
Abstract
OBJECTIVE Ebstein's anomaly is a rare congenital cardiac condition and data regarding pregnancy outcomes in this patient group are scarce. We evaluated the maternal and perinatal risks of pregnancy in 81 women with Ebstein's anomaly. METHODS The Registry of Pregnancy and Cardiac disease is a prospective global registry of pregnancies in women with structural cardiac disease. Pregnancy outcomes in women with Ebstein's anomaly were examined. The primary outcome was the occurrence of a major adverse cardiac event (MACE) defined as maternal mortality, heart failure, arrhythmia, thromboembolic event or endocarditis. Secondary endpoints were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation as well as right atrial and ventricular dimensions. RESULTS In the 81 women with Ebstein's anomaly (mean age 29.7±6.1 years, 46.9% nulliparous), MACE occurred in 8 (9.9%) pregnancies, mostly heart failure (n=6). There were no maternal deaths. Prepregnancy signs of heart failure were predictive for MACE. Almost half of the women were delivered by caesarean section (45.7%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and 4.9% of the infants had congenital heart disease. In the subgroup in which prepregnancy and postpregnancy data were available, there was no difference in tricuspid valve regurgitation grade or right atrial and ventricular dimensions before and after pregnancy. CONCLUSIONS Most women with Ebstein's anomaly tolerate pregnancy well, but women with prepregnancy signs of heart failure are at higher risk for MACE during pregnancy and should be counselled accordingly.
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Affiliation(s)
- Johanna A van der Zande
- Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Obstetrics and Gynecology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Oktay Tutarel
- Department of Congenital Heart Disease and Pediatric Cardiology, German Heart Centre, Munich, Germany
| | | | | | - Roberto Bordese
- Department of Pediatric Cardiology and Congenital Heart Disease, Regina Margherita Children's Hospital, Turin, Italy
| | - Elvin Zengin
- Department of Cardiology, University Medical Center Hamburg-Eppendorf University Heart & Vascular Center, Hamburg, Germany
| | - William E Wagner
- Department of Cardiology, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA
| | - Lidia de Sousa
- Department of Cardiology, Hospital de Santa Marta, Lisboa, Portugal
| | - Piers Clifford
- Department of Cardiology, Imperial College Healthcare NHS Trust, London, UK
| | - Mark R Johnson
- Department of Obstetric Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK
| | - Roger Hall
- Department of Cardiology, University of East Anglia Norwich Medical School, Norwich, UK
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Kittleson MM, DeFilippis EM, Bhagra CJ, Casale JP, Cauldwell M, Coscia LA, D'Souza R, Gaffney N, Gerovasili V, Ging P, Horsley K, Macera F, Mastrobattista JM, Paraskeva MA, Punnoose LR, Rasmusson KD, Reynaud Q, Ross HJ, Thakrar MV, Walsh MN. Reproductive health after thoracic transplantation: An ISHLT expert consensus statement. J Heart Lung Transplant 2023; 42:e1-e42. [PMID: 36528467 DOI: 10.1016/j.healun.2022.10.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations.
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Affiliation(s)
- Michelle M Kittleson
- Department of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
| | - Ersilia M DeFilippis
- Division of Cardiology, New York Presbyterian-Columbia University Irving Medical Center, New York, New York
| | - Catriona J Bhagra
- Department of Cardiology, Cambridge University and Royal Papworth NHS Foundation Trusts, Cambridge, UK
| | - Jillian P Casale
- Department of Pharmacy Services, University of Maryland Medical Center, Baltimore, Maryland
| | - Matthew Cauldwell
- Department of Obstetrics, Maternal Medicine Service, St George's Hospital, London, UK
| | - Lisa A Coscia
- Transplant Pregnancy Registry International, Gift of Life Institute, Philadelphia, Pennsylvania
| | - Rohan D'Souza
- Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
| | - Nicole Gaffney
- Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | | | - Patricia Ging
- Department of Pharmacy, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Kristin Horsley
- Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada
| | - Francesca Macera
- De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, Italy; Dept of Cardiology, Cliniques Universitaires de Bruxelles - Hôpital Erasme, Brussels, Belgium
| | - Joan M Mastrobattista
- Department of Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine Houston, Texas
| | - Miranda A Paraskeva
- Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia
| | - Lynn R Punnoose
- Vanderbilt Heart and Vascular Institute, Vanderbilt University Medical Center, Nashville, Tennessee
| | | | - Quitterie Reynaud
- Cystic Fibrosis Adult Referral Care Centre, Department of Internal Medicine, Hospices civils de Lyon, Pierre Bénite, France
| | - Heather J Ross
- Peter Munk Cardiac Centre of the University Health Network, Toronto, Ontario, Canada; Ted Rogers Centre for Heart Research, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada
| | - Mitesh V Thakrar
- Department of Medicine, Division of Respirology, University of Calgary, Calgary, Alberta, Canada
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Akalın M, Yalçın M, Demirci O, İsmailov H, Sahap Odacilar A, Dizdarogulları GE, Kahramanoğlu Ö, Ocal A, Akalın EE, Dizdaroğulları M. Positive effects of fetal echocardiography on maternal anxiety: a prospective study in a tertiary center in Turkey. J Psychosom Obstet Gynaecol 2022; 43:585-592. [PMID: 36137219 DOI: 10.1080/0167482x.2022.2124911] [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: 10/14/2022] Open
Abstract
Aim: The aim of this study was to determine the anxiety levels of pregnant women who were referred to a tertiary center for fetal echocardiography (FE) and the effect of FE results on maternal anxiety.Methods: This prospective study was conducted between January 2020 and February 2021 and included 118 pregnant women. The anxiety levels of the participants were evaluated with the Spielberger State-Trait Anxiety Inventory, which evaluates state (STAI-I) and trait (STAI-II) anxiety. STAI-I and STAI-II were administered to participants at first admission using a standard interview technique prior to FE. After the FE was completed, a structured interview was performed and the state anxiety index (STAI-I-R) was re-administered to the participants.Results: Severe congenital heart disease (CHD) was detected in 63 (53.4%) fetuses. The participants' mean STAI-I scores were significantly higher than their mean STAI-II scores (44.19 ± 8.56 and 41.98 ± 5.98, respectively, t = 2.59 and p = 0.011). In pregnant women with fetuses with severe CHD, STAI-I-R scores were significantly lower compared to STAI-I scores (43.48 ± 7.97 and 46.28 ± 7.18, respectively, t = 2.13 and p = 0.037).Conclusion: Referral for FE is associated with increased maternal anxiety, and a structured interview may result in reduced anxiety levels even in those with abnormal FE.
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Affiliation(s)
- Münip Akalın
- Department of Perinatology, Marmara University Pendik Training and Research Hospital, Istanbul, Turkey
| | - Murat Yalçın
- Department of Psychiatry, University of Health Sciences Erenköy Mental and Nervous Diseases Training and Research Hospital, Istanbul, Turkey
| | - Oya Demirci
- Department of Perinatology, University of Health Sciences Zeynep Kamil Women's and Children's Disease Training and Research Hospital, Istanbul, Turkey
| | - Hayal İsmailov
- Department of Perinatology, University of Health Sciences Zeynep Kamil Women's and Children's Disease Training and Research Hospital, Istanbul, Turkey
| | - Ali Sahap Odacilar
- Department of Perinatology, University of Health Sciences Zeynep Kamil Women's and Children's Disease Training and Research Hospital, Istanbul, Turkey
| | - Gizem Elif Dizdarogulları
- Department of Perinatology, University of Health Sciences Zeynep Kamil Women's and Children's Disease Training and Research Hospital, Istanbul, Turkey
| | - Özge Kahramanoğlu
- Department of Perinatology, University of Health Sciences Zeynep Kamil Women's and Children's Disease Training and Research Hospital, Istanbul, Turkey
| | - Aydın Ocal
- Department of Perinatology, University of Health Sciences Zeynep Kamil Women's and Children's Disease Training and Research Hospital, Istanbul, Turkey
| | - Emine Eda Akalın
- Department of Obstetrics and Gynaecology, Bahcesehir University School of Medicine, Istanbul, Turkey
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10
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Zhang X, Huangfu Z. Management of pregnant patients with pulmonary arterial hypertension. Front Cardiovasc Med 2022; 9:1029057. [PMID: 36440029 PMCID: PMC9684470 DOI: 10.3389/fcvm.2022.1029057] [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: 08/26/2022] [Accepted: 10/27/2022] [Indexed: 09/19/2023] Open
Abstract
Pregnant individuals with pulmonary arterial hypertension (PAH) have significantly high risks of maternal and perinatal mortality. Profound changes in plasma volume, cardiac output and systemic vascular resistance can all increase the strain being placed on the right ventricle, leading to heart failure and cardiovascular collapse. Given the complex network of opposing physiological changes, strict contraception and reduction of hemodynamic fluctuations during pregnancy are important methods of minimizing the risk of maternal mortality and improving the outcomes following pregnancy. In this review, we discuss the recent research progress into pre-conception management and the various therapeutic strategies for pregnant individuals with PAH.
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Affiliation(s)
- Xiao Zhang
- Department of Gynecology and Obstetrics, Beijing Hospital, National Center of Gerontology, Beijing, China
- Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
- Peking Union Medical College, Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Zhao Huangfu
- Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China
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11
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Rakha S, Mohy-Eldeen R, Al-Haggar M, El-Bayoumi MA. Recurrence pattern of non-syndromic familial congenital heart diseases among a large cohort of families from Egypt. BMC Pediatr 2022; 22:607. [PMID: 36258181 PMCID: PMC9580194 DOI: 10.1186/s12887-022-03640-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 09/09/2022] [Accepted: 09/26/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Congenital heart diseases (CHD) are the commonest congenital anomalies with increased risk in children born from families with affected members. However, various recurrence patterns of CHDs have been reported in different populations. Therefore, this work aimed to assess the recurrence patterns of CHDs in a large sample of Egyptian families. METHODS From January 2020 to October 2021, non-syndromic children with confirmed CHDs were recruited. Data were collected from guardians of the recruited children and hospital records, including the index case's cardiac diagnosis and CHD diagnosis of other affected family members with to determine their recurrence pattern, consanguinity, and multi-gestation status. RESULTS A total of 130 recurrent cases with CHD were documented in 1960 families of children with CHD, including 66,989 members. Most recurrences were detected among first-degree relatives 50/130 (38.46%), especially siblings. Discordant recurrence was the most detected pattern (45.38%), followed by concordant recurrence (42.31%), and the least was group concordance. Recurrence rate was the highest for septal defects with left ventricular outflow tract obstruction (LVOTO) (11.8%) and anomalous venous drainage (11.1%), followed by septal defect with right ventricular outflow tract obstruction (RVOTO) (9.4%), isolated ventricular septal defect (VSD) category (8.2%) and LVOTO (8%). Familial recurrence was significant in consanguineous marriages [p = 0.0001; OR (95%CI) = 4.5 (2.25-9.01)] and in multi-gestations siblings: [p = 0.036; OR (95%CI) = 12.5(1.03-6.04)]. CONCLUSION The recurrence of non-syndromic CHD is evident among first-degree relatives in Egyptian families, with mostly a discordant recurrence pattern. Recurrence was more notable in septal defects with LVOTO, anomalous venous drainage, septal defect with RVOTO, isolated VSD, and isolated LVOTO diagnostic categories. This finding will significantly impact family counseling, emphasizing higher recurrence in consanguineous parents.
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Affiliation(s)
- Shaimaa Rakha
- Pediatric Cardiology Unit, Pediatrics department, Faculty of Medicine, Mansoura University , El Gomhouria Street, 35516, Mansoura, Dakahlia Governorate, Egypt.
| | - Rehab Mohy-Eldeen
- Resident of Pediatrics, Mansoura University Children Hospital, Mansoura University, Mansoura, Egypt
| | - Mohammad Al-Haggar
- Genetics Unit, Pediatrics department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohammed Attia El-Bayoumi
- Intensive care Unit, Pediatrics department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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12
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Intrinsic myocardial defects underlie an Rbfox-deficient zebrafish model of hypoplastic left heart syndrome. Nat Commun 2022; 13:5877. [PMID: 36198703 PMCID: PMC9534849 DOI: 10.1038/s41467-022-32982-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 08/18/2022] [Indexed: 02/03/2023] Open
Abstract
Hypoplastic left heart syndrome (HLHS) is characterized by underdevelopment of left sided structures including the ventricle, valves, and aorta. Prevailing paradigm suggests that HLHS is a multigenic disease of co-occurring phenotypes. Here, we report that zebrafish lacking two orthologs of the RNA binding protein RBFOX2, a gene linked to HLHS in humans, display cardiovascular defects overlapping those in HLHS patients including ventricular, valve, and aortic deficiencies. In contrast to current models, we demonstrate that these structural deficits arise secondary to impaired pump function as these phenotypes are rescued when Rbfox is specifically expressed in the myocardium. Mechanistically, we find diminished expression and alternative splicing of sarcomere and mitochondrial components that compromise sarcomere assembly and mitochondrial respiration, respectively. Injection of human RBFOX2 mRNA restores cardiovascular development in rbfox mutant zebrafish, while HLHS-linked RBFOX2 variants fail to rescue. This work supports an emerging paradigm for HLHS pathogenesis that centers on myocardial intrinsic defects.
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13
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Abstract
The application of next-generation sequencing to study congenital heart disease (CHD) is increasingly providing new insights into the causes and mechanisms of this prevalent birth anomaly. Whole-exome sequencing analysis identifies damaging gene variants altering single or contiguous nucleotides that are assigned pathogenicity based on statistical analyses of families and cohorts with CHD, high expression in the developing heart and depletion of damaging protein-coding variants in the general population. Gene classes fulfilling these criteria are enriched in patients with CHD and extracardiac abnormalities, evidencing shared pathways in organogenesis. Developmental single-cell transcriptomic data demonstrate the expression of CHD-associated genes in particular cell lineages, and emerging insights indicate that genetic variants perturb multicellular interactions that are crucial for cardiogenesis. Whole-genome sequencing analyses extend these observations, identifying non-coding variants that influence the expression of genes associated with CHD and contribute to the estimated ~55% of unexplained cases of CHD. These approaches combined with the assessment of common and mosaic genetic variants have provided a more complete knowledge of the causes and mechanisms of CHD. Such advances provide knowledge to inform the clinical care of patients with CHD or other birth defects and deepen our understanding of the complexity of human development. In this Review, we highlight known and candidate CHD-associated human genes and discuss how the integration of advances in developmental biology research can provide new insights into the genetic contributions to CHD.
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Affiliation(s)
- Sarah U Morton
- Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Boston, MA, USA
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
- Department of Genetics, Harvard Medical School, Boston, MA, USA
| | - Daniel Quiat
- Department of Pediatrics, Harvard Medical School, Boston, MA, USA
- Department of Genetics, Harvard Medical School, Boston, MA, USA
- Department of Cardiology, Boston Children's Hospital, Boston, MA, USA
| | | | - Christine E Seidman
- Department of Genetics, Harvard Medical School, Boston, MA, USA.
- Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
- Howard Hughes Medical Institute, Harvard University, Boston, MA, USA.
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14
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Abstract
PURPOSE OF THE REVIEW The purpose of this review is to discuss the risk stratification and management of pregnancy in women with complex congenital heart disease. RECENT FINDINGS Classifying congenital heart defects (CHD) including both anatomy and physiology is important for maternal risk stratification. Although most women with CHD can tolerate the physiological challenge of pregnancy, some may experience serious risks both to their health and that of their foetus. The WHO maternal risk classification model remains the best-validated risk measure. Ideally, women with CHD should have pre-conception assessment with a CHD cardiologist. General principles of management, such as need for expert centre delivery, a multidisciplinary team, epidural and mode of delivery are based on WHO risk in combination with expert assessment of status. CHD is increasingly prevalent in women of child-bearing age. Assessment by an adult CHD cardiologist, ideally pre-conception, is key in assessing and minimising risk to mother and foetus.
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15
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Grewal J, Windram J, Bottega N, Sermer M, Spears D, Silversides C, Siu SC, Swan L. Canadian Cardiovascular Society: Clinical Practice Update on Cardiovascular Management of the Pregnant Patient. Can J Cardiol 2021; 37:1886-1901. [PMID: 34217807 DOI: 10.1016/j.cjca.2021.06.021] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 06/24/2021] [Accepted: 06/28/2021] [Indexed: 11/29/2022] Open
Abstract
The number of women of childbearing age with cardiovascular disease (CVD) is growing due to increased survival of children with congenital heart disease (CHD). More women are also becoming pregnant at an older age, which is associated with increased co-morbidities including hypertension, diabetes and acquired CVD. Over the last decade the field of cardio-obstetrics has significantly advanced with the development of multidisciplinary cardio-obstetric programs (COPs) to address the increasing burden of CVD in pregnancy. With the introduction of formal COPs, pregnancy outcomes in women with heart disease have improved. COPs provide preconception counseling, antenatal and postpartum cardiac surveillance, labor and delivery planning. Pre-pregnancy counseling by a COP should be offered to women with suspected CVD who are of child bearing age. In those women who present while pregnant, counseling should be performed by a COP as early as possible in pregnancy. The purpose of counseling is to reduce the risk of pregnancy to the mother and fetus whenever possible. This is done through accurate maternal and fetal risk stratification, optimizing cardiac lesions, reviewing safety of medications in pregnancy, and making a detailed plan for the pregnancy, labor and delivery. This Clinical Practice Update highlights the COP approach to pre-pregnancy counseling, risk stratification, and management of commonly encountered cardiac conditions through pregnancy. We highlight "red flags" that should trigger a more timely assessment by a COP. We also describe the approach to some of the cardiac emergencies that the care provider may encounter in a pregnant woman.
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Affiliation(s)
- Jasmine Grewal
- Division of Cardiology, St.Paul's Hospital, University of British Columbia, Vancouver, B.C., Canada.
| | - Jonathan Windram
- Department of Cardiology, Mazankowski Heart Institute, University of Alberta, Edmonton, AB, Canada
| | - Natalie Bottega
- Department of Cardiology, Royal Victoria Hospital-Glen Site, McGill University, Montréal, QC, Canada
| | - Mathew Sermer
- Department of Obstetrics and Gynaecology, Mount Sinai Hospital, University of Toronto, Toronto ON
| | - Danna Spears
- Division of Cardiology, University Health Network, Toronto General Hospital, Toronto, Ontario, Canada
| | - Candice Silversides
- Division of Cardiology, University Health Network, Toronto General Hospital, Toronto, Ontario, Canada; Division of Cardiology Department of Medicine Mount Sinai Hospital and University Health NetworkUniversity of Toronto Canada
| | - Samuel C Siu
- Division of Cardiology Department of Medicine Mount Sinai Hospital and University Health NetworkUniversity of Toronto Canada; Maternal Cardiology Program Division of Cardiology Department of Medicine Schulich School of Medicine and Dentistry London Ontario Canada
| | - Lorna Swan
- Division of Cardiology, University Health Network, Toronto General Hospital, Toronto, Ontario, Canada; Division of Cardiology Department of Medicine Mount Sinai Hospital and University Health NetworkUniversity of Toronto Canada
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16
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Zaban NB, Darragh RK, Parent JJ. Fetal Echocardiography is Useful for Screening Fetuses with a Family History of Cardiomyopathy. Pediatr Cardiol 2020; 41:1766-1772. [PMID: 32844298 DOI: 10.1007/s00246-020-02439-3] [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: 04/14/2020] [Accepted: 08/17/2020] [Indexed: 10/23/2022]
Abstract
We screened all fetal echocardiograms performed at our institution for the past 5 years for the indication of family history of cardiomyopathy. Twenty-six patients were identified who had fetal echocardiograms performed due to a family history of cardiomyopathy. Three out of 26 patients (11.5%) had findings of decreased ventricular function and dilation consistent with cardiomyopathy. All who had cardiomyopathy on fetal echocardiography had parents with genetic mutations (2 maternal, 1 paternal), including one mother who had a cardiac transplant at age 8 for dilated cardiomyopathy. All 3 affected infants had prenatal planning for high level care and were transferred to our facility immediately after birth for cardiology evaluation and management. 2 patients required inotropic support in the newborn period. One patient was transplanted at age 2 months. One patient required ECMO support for one week and initially recovered, but subsequently required mechanical support and listing for heart transplant. We recommend patients with a strong family history of cardiomyopathy in either parent, especially those with known genetic mutations associated with cardiomyopathy, have fetal echocardiograms performed.
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Affiliation(s)
- Nicholas B Zaban
- Division of Pediatric Cardiology, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA.,CentraCare Heart and Vascular Center, 1200 6th Ave N, St. Cloud, MN, 56303, USA
| | - Robert K Darragh
- Division of Pediatric Cardiology, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
| | - John J Parent
- Division of Pediatric Cardiology, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA. .,Division of Pediatric Cardiology, Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, 705 Riley Hospital Drive, Suite RR 127, Indianapolis, IN, 46254, USA.
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17
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Screening and evaluation of newly diagnosed cardiovascular diseases in first-trimester asymptomatic pregnant women in a tertiary antenatal care center in Turkey. Anatol J Cardiol 2020; 23:99-104. [PMID: 32011322 PMCID: PMC7040868 DOI: 10.14744/anatoljcardiol.2019.55267] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
OBJECTIVE Cardiovascular disease (CVD) is the leading cause of death during pregnancy. Therefore, its detection early in pregnancy is of great importance. In this study, we aimed to investigate the rate and spectrum of CVD among healthy women in the first trimester of pregnancy. METHODS A total of 900 women in the first trimester of pregnancy, who attended the antenatal outpatient clinic of a tertiary care center in Ankara, Turkey, for a routine pregnancy examination, were recruited into this prospective study. Patients with a history of chronic systemic diseases, CVD, and/or a family history of an early onset CVD, and multiple pregnancies were excluded. Patients who were included in the study underwent electrocardiography and transthoracic echocardiography by the same cardiologist. RESULTS The rate of newly diagnosed CVD cases among asymptomatic pregnant women without any cardiac or clinical risk factors was 5.2% (n=47). The following CVDs were detected: rheumatic heart disease (n=26; 55.3%), congenital heart disease (n=13; 27.6%), and isolated valve disease (moderate and severe) (n=8; 17%). The mitral valve prolapse was detected in 32 women (3.5%) and atrial septal aneurysm in 51 women (5.67%). Thirty women (3.3%) had arrhythmia. CONCLUSION The CVD rate of 5.2% among healthy women in the first trimester of pregnancy shows that the clinicians must keep in mind that during pregnancy, physiological changes in the cardiovascular system may aggravate an undiagnosed disease, and they should be alert even in case of mild cardiac symptoms that may interfere with pregnancy complaints.
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18
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Affiliation(s)
- Iris M van Hagen
- Cardiology, Erasmus Medical Center, Rotterdam, Zuid-Holland, The Netherlands
- Cardiology, Maasstad Hospital, Rotterdam, Zuid-Holland, The Netherlands
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19
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Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, Crumb SR, Dearani JA, Fuller S, Gurvitz M, Khairy P, Landzberg MJ, Saidi A, Valente AM, Van Hare GF. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2020; 139:e637-e697. [PMID: 30586768 DOI: 10.1161/cir.0000000000000602] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Karen K Stout
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Curt J Daniels
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Jamil A Aboulhosn
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Biykem Bozkurt
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Craig S Broberg
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Jack M Colman
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Stephen R Crumb
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Joseph A Dearani
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Stephanie Fuller
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Michelle Gurvitz
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Paul Khairy
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Michael J Landzberg
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Arwa Saidi
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - Anne Marie Valente
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
| | - George F Van Hare
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative. §§Former Task Force member; current member during the writing effort
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20
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Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, Crumb SR, Dearani JA, Fuller S, Gurvitz M, Khairy P, Landzberg MJ, Saidi A, Valente AM, Van Hare GF. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2020; 139:e698-e800. [PMID: 30586767 DOI: 10.1161/cir.0000000000000603] [Citation(s) in RCA: 277] [Impact Index Per Article: 55.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Karen K Stout
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Curt J Daniels
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Jamil A Aboulhosn
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Biykem Bozkurt
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Craig S Broberg
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Jack M Colman
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Stephen R Crumb
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Joseph A Dearani
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Stephanie Fuller
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Michelle Gurvitz
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Paul Khairy
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Michael J Landzberg
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Arwa Saidi
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - Anne Marie Valente
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
| | - George F Van Hare
- Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for recusal information. †ACC/AHA Representative. ‡International Society for Adult Congenital Heart Disease Representative. §Society for Cardiovascular Angiography and Interventions Representative. ‖ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ¶Society of Thoracic Surgeons Representative. #American Association for Thoracic Surgery Representative. **ACC/AHA Task Force on Performance Measures Liaison. ††American Society of Echocardiography Representative. ‡‡Heart Rhythm Society Representative
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21
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Ellesøe SG, Workman CT, Bouvagnet P, Loffredo CA, McBride KL, Hinton RB, van Engelen K, Gertsen EC, Mulder BJM, Postma AV, Anderson RH, Hjortdal VE, Brunak S, Larsen LA. Familial co-occurrence of congenital heart defects follows distinct patterns. Eur Heart J 2019; 39:1015-1022. [PMID: 29106500 PMCID: PMC6018923 DOI: 10.1093/eurheartj/ehx314] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Accepted: 06/01/2017] [Indexed: 12/16/2022] Open
Abstract
Aims Congenital heart defects (CHD) affect almost 1% of all live born children and the number of adults with CHD is increasing. In families where CHD has occurred previously, estimates of recurrence risk, and the type of recurring malformation are important for counselling and clinical decision-making, but the recurrence patterns in families are poorly understood. We aimed to determine recurrence patterns, by investigating the co-occurrences of CHD in 1163 families with known malformations, comprising 3080 individuals with clinically confirmed diagnosis. Methods and results We calculated rates of concordance and discordance for 41 specific types of malformations, observing a high variability in the rates of concordance and discordance. By calculating odds ratios for each of 1640 pairs of discordant lesions observed between affected family members, we were able to identify 178 pairs of malformations that co-occurred significantly more or less often than expected in families. The data show that distinct groups of cardiac malformations co-occur in families, suggesting influence from underlying developmental mechanisms. Analysis of human and mouse susceptibility genes showed that they were shared in 19% and 20% of pairs of co-occurring discordant malformations, respectively, but none of malformations that rarely co-occur, suggesting that a significant proportion of co-occurring lesions in families is caused by overlapping susceptibility genes. Conclusion Familial CHD follow specific patterns of recurrence, suggesting a strong influence from genetically regulated developmental mechanisms. Co-occurrence of malformations in families is caused by shared susceptibility genes.
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Affiliation(s)
- Sabrina G Ellesøe
- Programme for Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
| | - Christopher T Workman
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
| | - Patrice Bouvagnet
- Laboratoire Cardiogénétique, Hospices Civils de Lyon, Groupe Hospitalier Est, 59 boulevard Pinel, CBPE, 69677, Bron, France
| | - Christopher A Loffredo
- Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Road, Washington, DC 20057-1472, USA
| | - Kim L McBride
- Center for Cardiovascular Research, Nationwide Children's Hospital, and Department of Pediatrics, Ohio State University, 700 Children's Drive Columbus, OH 43205, Columbus, OH, USA
| | - Robert B Hinton
- Division of Cardiology, The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2003, Cincinnati, OH, 45229, USA
| | - Klaartje van Engelen
- Department of Clinical Genetics, Academic Medical Centre, Meibergdreef 15, Amsterdam 1105 AZ, The Netherlands.,Department of Clinical Genetics, VU University, De Boelelaan 1117, NL-1081 HV Amsterdam, The Netherlands
| | - Emma C Gertsen
- Department of Clinical Genetics, Academic Medical Centre, Meibergdreef 15, Amsterdam 1105 AZ, The Netherlands
| | - Barbara J M Mulder
- Department of Cardiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands
| | - Alex V Postma
- Department of Clinical Genetics, Academic Medical Centre, Meibergdreef 15, Amsterdam 1105 AZ, The Netherlands.,Department of Anatomy, Embryology & Physiology, Academic Medical Centre, Meibergdreef 15, Amsterdam 1105 AZ, The Netherlands
| | - Robert H Anderson
- Institute of Genetic Medicine, Newcastle University, Central Pkwy, Newcastle upon Tyne NE1 3BZ, UK
| | - Vibeke E Hjortdal
- Department of Cardiothoracic Surgery, Aarhus University Hospital, Skejby, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark
| | - Søren Brunak
- Programme for Disease Systems Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
| | - Lars A Larsen
- Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark
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22
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Haberer K, Silversides CK. Congenital Heart Disease and Women's Health Across the Life Span: Focus on Reproductive Issues. Can J Cardiol 2019; 35:1652-1663. [PMID: 31813502 DOI: 10.1016/j.cjca.2019.10.009] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 10/01/2019] [Accepted: 10/01/2019] [Indexed: 01/11/2023] Open
Abstract
From adolescence to older age, women with congenital heart disease (CHD) face unique challenges. In this review we explore the ways in which CHD affects women's sexual and reproductive health and, in turn, how their sexual and reproductive history affects the course of their CHD. In adolescence, special attention must be paid to menstrual irregularities and concerns of developing sexuality and self-image. Discussions about sexuality and reproduction are an important part of transition planning and must be done with an awareness of the adolescent's developing understanding and maturity. Pregnancy imposes a hemodynamic load on the heart which may lead to cardiac, obstetric, and fetal/neonatal complications in women with CHD. Prepregnancy counselling must include an assessment of maternal and fetal risk according to several well developed models. Counselling should also include discussions about fertility and alternatives to pregnancy when appropriate. Recommendations for contraception must be made according to the patient's cardiac lesion. In caring for women with CHD during pregnancy, a multidisciplinary cardio-obstetrics team is recommended to optimize care. More research is needed into the long-term impact of pregnancy on the prognosis of patients with CHD. As women with CHD increasingly survive into old age, more attention will need to be directed toward the treatment of menopause and acquired heart disease in this population.
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Affiliation(s)
- Kim Haberer
- Division of Cardiology, University of Toronto Pregnancy and Heart Disease Program, Mount Sinai and Toronto General Hospitals, Toronto, Ontario, Canada
| | - Candice K Silversides
- Division of Cardiology, University of Toronto Pregnancy and Heart Disease Program, Mount Sinai and Toronto General Hospitals, Toronto, Ontario, Canada.
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23
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Risk factors for congenital heart defects in two populations residing in the same geographic area: a long-term population-based study, Southern Israel. Cardiol Young 2019; 29:1040-1044. [PMID: 31287039 DOI: 10.1017/s1047951119001409] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND Congenital Heart Defects (CHD) are the most common structural defects of newborns. Southern Israel's population is comprised of Jews (75%) and Arab-Bedouins (25%). The latter has a high rate of consanguinity and low abortion rate compared with the Jewish population, which led us to suspect a higher CHD prevalence in this population. Our aim was to compare maternal risk factors that are associated with CHD in these populations. METHODS All births during 1991-2011 in Soroka University Medical Center (n = 247, 289) with 6078 newborns having CHD were included. To account for same-woman deliveries, general estimating equation models adjusted for ethnicity, gender and birth number were used. RESULTS The total prevalence of CHD was 24.6/1000 live births, with 21.4 and 30 among Jewish and Bedouin populations, respectively, (p = 0.001). Multi-variant analysis of risk factors for CHD revealed that risk factors common to both populations included conception with fertility medications, sibling CHD, maternal CHD, diabetes mellitus, hypertension and anaemia. Risk factors that were specific for the Bedouin population were - maternal age over 35 years, recurrent pregnancy loss and in vitro fertilisation. However, sibling CHD was more common as a CHD risk factor in the Jewish compared with the Bedouin population (Adjusted OR 10.23 versus 3.19, respectively). CONCLUSIONS The prevalence of CHD is higher in both the Bedouin and Jewish populations than previously reported. Several maternal factors were associated with CHD specifically for a certain population. Risk factors for CHD vary in populations residing in the same geographic area.
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24
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Llurba Olive E, Xiao E, Natale DR, Fisher SA. Oxygen and lack of oxygen in fetal and placental development, feto-placental coupling, and congenital heart defects. Birth Defects Res 2019; 110:1517-1530. [PMID: 30576091 DOI: 10.1002/bdr2.1430] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 11/12/2018] [Indexed: 12/19/2022]
Abstract
Low oxygen concentration (hypoxia) is part of normal embryonic development, yet the situation is complex. Oxygen (O2 ) is a janus gas with low levels signaling through hypoxia-inducible transcription factor (HIF) that are required for development of fetal and placental vasculature and fetal red blood cells. This results in coupling of fetus and mother around midgestation as a functional feto-placental unit (FPU) for O2 transport, which is required for continued growth and development of the fetus. Defects in these processes may leave the developing fetus vulnerable to O2 deprivation or other stressors during this critical midgestational transition when common septal and conotruncal heart defects (CHDs) are likely to arise. Recent human epidemiological and case-control studies support an association between placental dysfunction, manifest as early onset pre-eclampsia (PE) and increased serum bio-markers, and CHD. Animal studies support this association, in particular those using gene inactivation in the mouse. Sophisticated methods for gene inactivation, cell fate mapping, and a quantitative bio-reporter of O2 concentration support the premise that hypoxic stress at critical stages of development leads to CHD. The secondary heart field contributing to the cardiac outlet is a key target, with activation of the un-folded protein response and abrogation of FGF signaling or precocious activation of a cardiomyocyte transcriptional program for differentiation, suggested as mechanisms. These studies provide a strong foundation for further study of feto-placental coupling and hypoxic stress in the genesis of human CHD.
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Affiliation(s)
- Elisa Llurba Olive
- Director of the Obstetrics and Gynecology Department, Sant Pau University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.,Maternal and Child Health and Development Network II (SAMID II) RD16/0022, Institute of Health Carlos III, Madrid, Spain
| | - Emily Xiao
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.,Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland
| | - David R Natale
- Department of Obstetrics and Gynecology and Reproductive Sciences, University of California San Diego, San Diego, California
| | - Steven A Fisher
- Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland.,Department of Physiology and Biophysics, University of Maryland School of Medicine, Baltimore, Maryland
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25
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Rajapreyar IN, Sinkey RG, Joly JM, Pamboukian SV, Lenneman A, Hoopes CW, Kopf S, Hayes A, Moussa H, Acharya D, Aryal S, Weeks P, Cribbs M, Wetta L, Tallaj J. Management of reproductive health after cardiac transplantation. J Matern Fetal Neonatal Med 2019; 34:1469-1478. [PMID: 31238747 DOI: 10.1080/14767058.2019.1636962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Pregnancy after cardiac transplantation poses immense challenges. Maternal risks include hypertensive disorders of pregnancy, rejection, and failure of the cardiac allograft that may lead to death. Fetal risks include potential teratogenic effects of immunosuppression and prematurity. Because of the high-risk nature of pregnancy in a heart transplant patient, management of reproductive health after cardiac transplantation should include preconception counseling to all women in the reproductive age group before and after cardiac transplantation. Reliable contraception is vital as nearly half of the pregnancies in this population are unintended. Despite the associated risks, successful pregnancies after cardiac transplantation have been reported. A multidisciplinary approach proposed in this review is essential for successful outcomes. A checklist for providers to guide management is provided.
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Affiliation(s)
- Indranee N Rajapreyar
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rachel G Sinkey
- Department of Obstetrics and Gynecology, Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Joanna M Joly
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA.,Birmingham VA Medical Center, Birmingham, AL, USA
| | - Salpy V Pamboukian
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Andrew Lenneman
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Charles W Hoopes
- Department of Surgery, Division of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sabrina Kopf
- Department of Transplant Operations, Cardiothoracic Transplant Program, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Allison Hayes
- Department of Transplant Operations, Cardiothoracic Transplant Program, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Hind Moussa
- Department of Obstetrics and Gynecology and Maternal Fetal Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Deepak Acharya
- Department of Medicine, Division of Cardiology, University of Arizona College of Medicine, Tucson, AZ, USA
| | - Sudeep Aryal
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Phillip Weeks
- Department of Pharmacy, Memorial Hermann Texas Medical Center, Houston, TX, USA
| | - Marc Cribbs
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Luisa Wetta
- Department of Obstetrics and Gynecology, Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Jose Tallaj
- Department of Medicine, Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA.,Birmingham VA Medical Center, Birmingham, AL, USA
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26
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Yokouchi-Konishi T, Yoshimatsu J, Sawada M, Shionoiri T, Nakanishi A, Horiuchi C, Tsuritani M, Iwanaga N, Kamiya CA, Neki R, Miyake A, Kurosaki K, Shiraishi I. Recurrent Congenital Heart Diseases Among Neonates Born to Mothers with Congenital Heart Diseases. Pediatr Cardiol 2019; 40:865-870. [PMID: 30830281 DOI: 10.1007/s00246-019-02083-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 02/27/2019] [Indexed: 01/08/2023]
Abstract
The frequency of newborns with congenital heart disease (CHD) is approximately 1% in the general population; however, the recurrence rate of CHD in mothers with CHD differs in ethnicity and reports. We therefore aimed to determine the prevalence of CHD among neonates born to mothers with CHD in our institute in Japan. We reviewed the medical charts of 803 neonates delivered by 529 women with CHD at the National Cerebral and Cardiovascular Center from 1982 to 2016. They included isolated ventricular septal defect (VSD,31.4%), isolated atrial septal defect (ASD, 23.3%), tetralogy of Fallot (TOF,10.6%). We defined CHD in neonates as being diagnosed within 1 month of birth. We estimated that the average rate of the CHD recurrence was 3.1%. The recurrence ratios in each maternal CHD were 8.6%, 7.1%, 6.2%, 4.8%, 3.6%, and 1.5% for PS, CoA, TOF, atrioventricular septal defect, VSD, and ASD, respectively. The rate of CHD in offsprings whose mothers have CHD was 3 times greater than that of mothers with healthy hearts. Almost half of neonates with CHD had the same phenotype as their mother in our series. Especially, PS and CoA were closely related to the type of maternal CHD.
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Affiliation(s)
- Tae Yokouchi-Konishi
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan.
| | - Jun Yoshimatsu
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Masami Sawada
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Tadasu Shionoiri
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Atsushi Nakanishi
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Chinami Horiuchi
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Mitsuhiro Tsuritani
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Naoko Iwanaga
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Chizuko A Kamiya
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Reiko Neki
- Department of Perinatology and Gynecology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, 565-8565, Japan
| | - Akira Miyake
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Kenichi Kurosaki
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Isao Shiraishi
- Department of Pediatric Cardiology, National Cerebral and Cardiovascular Center, Osaka, Japan
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27
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Pasupathy D, Denbow ML, Rutherford MA. The Combined Use of Ultrasound and Fetal Magnetic Resonance Imaging for a Comprehensive Fetal Neurological Assessment in Fetal Congenital Cardiac Defects: Scientific Impact Paper No. 60. BJOG 2019; 126:e142-e151. [PMID: 30916430 DOI: 10.1111/1471-0528.15620] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Heart problems are common in newborn babies, affecting approximately 5-10 in 1000 babies. Some are more serious than others, but most babies born with heart problems do not have other health issues. Of those babies who have a serious heart problem, almost 1 in 4 will have heart surgery in their first year. In the UK, pregnant women are offered a scan at around 20 weeks to try and spot any heart problems. In most cases there is not a clear reason for the problem, but sometimes other issues, such as genetic conditions, are discovered. In recent years the care given to these babies after they are born has improved their chances of surviving. However, it is recognised that babies born with heart problems have a risk of delays in their learning and development. This may be due to their medical condition, or as a result of surgery and complications after birth. In babies with heart problems, there is a need for more research on ultrasound and magnetic resonance imaging (MRI) to understand how the brain develops and why these babies are more likely to have delays in learning and development. This paper discusses the way ultrasound and MRI are used in assessing the baby's brain. Ultrasound is often used to spot any problems, looking at how the baby's brain develops in pregnancy. Advances in ultrasound technologies have made this easier. MRI is well-established and safe in pregnancy, and if problems in the brain have been seen on ultrasound, MRI may be used to look at these problems in more detail. While it is not always clear what unusual MRI findings can mean for the baby in the long term, increased understanding may mean parents can be given more information about possible outcomes for the baby and may help to improve the counselling they are offered before their baby's birth.
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28
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Pierpont ME, Brueckner M, Chung WK, Garg V, Lacro RV, McGuire AL, Mital S, Priest JR, Pu WT, Roberts A, Ware SM, Gelb BD, Russell MW. Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association. Circulation 2018; 138:e653-e711. [PMID: 30571578 PMCID: PMC6555769 DOI: 10.1161/cir.0000000000000606] [Citation(s) in RCA: 392] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This review provides an updated summary of the state of our knowledge of the genetic contributions to the pathogenesis of congenital heart disease. Since 2007, when the initial American Heart Association scientific statement on the genetic basis of congenital heart disease was published, new genomic techniques have become widely available that have dramatically changed our understanding of the causes of congenital heart disease and, clinically, have allowed more accurate definition of the pathogeneses of congenital heart disease in patients of all ages and even prenatally. Information is presented on new molecular testing techniques and their application to congenital heart disease, both isolated and associated with other congenital anomalies or syndromes. Recent advances in the understanding of copy number variants, syndromes, RASopathies, and heterotaxy/ciliopathies are provided. Insights into new research with congenital heart disease models, including genetically manipulated animals such as mice, chicks, and zebrafish, as well as human induced pluripotent stem cell-based approaches are provided to allow an understanding of how future research breakthroughs for congenital heart disease are likely to happen. It is anticipated that this review will provide a large range of health care-related personnel, including pediatric cardiologists, pediatricians, adult cardiologists, thoracic surgeons, obstetricians, geneticists, genetic counselors, and other related clinicians, timely information on the genetic aspects of congenital heart disease. The objective is to provide a comprehensive basis for interdisciplinary care for those with congenital heart disease.
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29
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Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J 2018; 39:3165-3241. [PMID: 30165544 DOI: 10.1093/eurheartj/ehy340] [Citation(s) in RCA: 1292] [Impact Index Per Article: 184.6] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, Crumb SR, Dearani JA, Fuller S, Gurvitz M, Khairy P, Landzberg MJ, Saidi A, Valente AM, Van Hare GF. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018; 73:e81-e192. [PMID: 30121239 DOI: 10.1016/j.jacc.2018.08.1029] [Citation(s) in RCA: 589] [Impact Index Per Article: 84.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018; 73:1494-1563. [PMID: 30121240 DOI: 10.1016/j.jacc.2018.08.1028] [Citation(s) in RCA: 394] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Razmara E, Garshasbi M. Whole-exome sequencing identifies R1279X of MYH6 gene to be associated with congenital heart disease. BMC Cardiovasc Disord 2018; 18:137. [PMID: 29969989 PMCID: PMC6029398 DOI: 10.1186/s12872-018-0867-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 06/20/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Myosin VI, encoded by MYH6, is expressed dominantly in human cardiac atria and plays consequential roles in cardiac muscle contraction and comprising the cardiac muscle thick filament. It has been reported that the mutations in the MYH6 gene associated with sinus venosus atrial septal defect (ASD type III), hypertrophic (HCM) and dilated (DCM) cardiomyopathies. METHODS Two patients in an Iranian family have been identified who affected to Congenital Heart Disease (CHD). The male patient, besides CHD, shows that the thyroglossal sinus, refractive errors of the eye and mitral stenosis. The first symptoms emerged at the birth and diagnosis based on clinical features was made at about 5 years. The family had a history of ASD. For recognizing mutated gene (s), whole exome sequencing (WES) was performed for the male patient and variants were analyzed by autosomal dominant inheritance mode. RESULTS Eventually, by several filtering processes, a mutation in MYH6 gene (NM_002471.3), c.3835C > T; R1279X, was identified as the most likely disease-susceptibility variant and then confirmed by Sanger sequencing in the family. The mutation frequency was checked out in the local databases. This mutation results in the elimination of the 660 amino acids in the C-terminal of Myosin VI protein, including the vital parts of the coiled-coil structure of the tail domain. CONCLUSIONS Our study represents the first case of Sinus venosus defect caused directly by MYH6 stop codon mutation. Our data indicate that by increase haploinsufficiency of myosin VI, c.3835C > T mutation with reduced penetrance could be associated with CHD.
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Affiliation(s)
- Ehsan Razmara
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Masoud Garshasbi
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
- Department of Medical Genetics, DeNA laboratory, Tehran, Iran
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Pavlicek J, Klaskova E, Prochazka M, Dolezalkova E, Matura D, Spacek R, Simetka O, Gruszka T, Polanska S, Kacerovsky M. Congenital heart defects according to the types of the risk factors - a single center experience. J Matern Fetal Neonatal Med 2018; 32:3606-3611. [PMID: 29681196 DOI: 10.1080/14767058.2018.1468883] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Objective: The main aim of this study was to compare the prevalence of congenital heart defects (CHDs) between pregnant women with and those without the risk factors. The secondary aim was to determine the influence of the specific risk factors, divided into subgroups, on the development of the CHD. Methods: The presented results were obtained over the course of a 15-year study between years 2002 and 2016. Fetal echocardiography was performed as a planned screening examination during the second trimester of gravidity. A total of 35,831 singleton pregnancies were examined at our center. Risk factors for the development of CHDs were analyzed and divide into the following groups: (i) maternal age ≥35 years; (ii) mother-related risk factors; (iii) pregnancy- and fetus-related risk factors; (iv) pregnancy after in vitro fertilization (IVF); (v) history of CHDs in the first-degree family member; (vi) history of CHDs in the second-degree family member; and (vii) positive genetic family history. Results: The risk factors were identified in 25% (8990/35,831) of pregnancies. In total, CHDs were detected in 1.1% (394/35,831) of fetuses. The prevalence rate of CHDs was higher in the pregnancies with than in those without the risk factors (2.5% [221/8990] versus 0.6% [173/26,841]; p < .0001). The presence of pregnancy- and fetus-related risk factors (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.3-9.7) and pregnancy after IVF (OR, 2.8; 95% CI, 1.5-5.2) were found to be independent risk factors of CHDs. Conclusions: The presence of specific risk factors is related to the increasing prevalence of CHDs. Pregnancy- and fetus-related risk factors and in vitro fertilization were found to be the independent risk factors of CHD.
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Affiliation(s)
- Jan Pavlicek
- a Department of Pediatrics and Prenatal Cardiology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - Eva Klaskova
- b Department of Pediatrics , University Hospital and Palacky University , Olomouc , Czech Republic
| | - Martin Prochazka
- c Department of Medical Genetics , University Hospital and Palacky University , Olomouc , Czech Republic
| | - Erika Dolezalkova
- d Department of Obstetrics and Gynecology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - David Matura
- d Department of Obstetrics and Gynecology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - Richard Spacek
- d Department of Obstetrics and Gynecology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - Ondrej Simetka
- d Department of Obstetrics and Gynecology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - Tomas Gruszka
- a Department of Pediatrics and Prenatal Cardiology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - Slavka Polanska
- a Department of Pediatrics and Prenatal Cardiology , University Hospital Ostrava, Faculty of Medicine in Ostrava , Ostrava , Czech Republic
| | - Marian Kacerovsky
- e Department of Obstetrics and Gynecology , Charles University, Faculty of Medicine in Hradec Kralove, University Hospital in Hradec Králové , Hradec Králové, Czech Republic.,f Biomedical Research Center , University Hospital Hradec Kralove , Hradec Králové , Czech Republic
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Klena NT, Gibbs BC, Lo CW. Cilia and Ciliopathies in Congenital Heart Disease. Cold Spring Harb Perspect Biol 2017; 9:cshperspect.a028266. [PMID: 28159874 DOI: 10.1101/cshperspect.a028266] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
A central role for cilia in congenital heart disease (CHD) was recently identified in a large-scale mouse mutagenesis screen. Although the screen was phenotype-driven, the majority of genes recovered were cilia-related, suggesting that cilia play a central role in CHD pathogenesis. This partly reflects the role of cilia as a hub for cell signaling pathways regulating cardiovascular development. Consistent with this, many cilia-transduced cell signaling genes were also recovered, and genes regulating vesicular trafficking, a pathway essential for ciliogenesis and cell signaling. Interestingly, among CHD-cilia genes recovered, some regulate left-right patterning, indicating cardiac left-right asymmetry disturbance may play significant roles in CHD pathogenesis. Clinically, CHD patients show a high prevalence of ciliary dysfunction and show enrichment for de novo mutations in cilia-related pathways. Combined with the mouse findings, this would suggest CHD may be a new class of ciliopathy.
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Affiliation(s)
- Nikolai T Klena
- Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201
| | - Brian C Gibbs
- Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201
| | - Cecilia W Lo
- Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201
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The complex genetics of hypoplastic left heart syndrome. Nat Genet 2017; 49:1152-1159. [PMID: 28530678 DOI: 10.1038/ng.3870] [Citation(s) in RCA: 168] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 04/24/2017] [Indexed: 12/11/2022]
Abstract
Congenital heart disease (CHD) affects up to 1% of live births. Although a genetic etiology is indicated by an increased recurrence risk, sporadic occurrence suggests that CHD genetics is complex. Here, we show that hypoplastic left heart syndrome (HLHS), a severe CHD, is multigenic and genetically heterogeneous. Using mouse forward genetics, we report what is, to our knowledge, the first isolation of HLHS mutant mice and identification of genes causing HLHS. Mutations from seven HLHS mouse lines showed multigenic enrichment in ten human chromosome regions linked to HLHS. Mutations in Sap130 and Pcdha9, genes not previously associated with CHD, were validated by CRISPR-Cas9 genome editing in mice as being digenic causes of HLHS. We also identified one subject with HLHS with SAP130 and PCDHA13 mutations. Mouse and zebrafish modeling showed that Sap130 mediates left ventricular hypoplasia, whereas Pcdha9 increases penetrance of aortic valve abnormalities, both signature HLHS defects. These findings show that HLHS can arise genetically in a combinatorial fashion, thus providing a new paradigm for the complex genetics of CHD.
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Brodwall K, Greve G, Leirgul E, Tell GS, Vollset SE, Øyen N. Recurrence of congenital heart defects among siblings-a nationwide study. Am J Med Genet A 2017; 173:1575-1585. [DOI: 10.1002/ajmg.a.38237] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Accepted: 03/06/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Kristoffer Brodwall
- Department of Global Public Health and Primary Care; University of Bergen; Bergen Norway
- Department of Pediatrics; Haukeland University Hospital; Bergen Norway
| | - Gottfried Greve
- Department of Medical Science; University of Bergen; Bergen Norway
- Department of Heart Disease; Haukeland University Hospital; Bergen Norway
| | - Elisabeth Leirgul
- Department of Global Public Health and Primary Care; University of Bergen; Bergen Norway
- Department of Heart Disease; Haukeland University Hospital; Bergen Norway
| | - Grethe S. Tell
- Department of Global Public Health and Primary Care; University of Bergen; Bergen Norway
- Norwegian Institute of Public Health; Bergen Norway
| | - Stein E. Vollset
- Department of Global Public Health and Primary Care; University of Bergen; Bergen Norway
- Norwegian Institute of Public Health; Oslo Norway
| | - Nina Øyen
- Department of Global Public Health and Primary Care; University of Bergen; Bergen Norway
- Center for Medical Genetics and Molecular Medicine; Haukeland University Hospital; Bergen Norway
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Bijanzadeh M. The recurrence risk of genetic complex diseases. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2017; 22:32. [PMID: 28461818 PMCID: PMC5390543 DOI: 10.4103/1735-1995.202143] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 10/30/2016] [Accepted: 12/18/2016] [Indexed: 12/19/2022]
Abstract
Complex inherited diseases affected by an interaction between collective effects of the genotype at one or multiple loci either to increase or to lower susceptibility to disease, combined with a variety of environmental exposures that may trigger, accelerate, exacerbate, or protect against the disease process. The new aspects of genetic techniques have been opened for diagnosis and analysis of inherited disorders. While appropriate Mendelian laws is applied to estimate the recurrence risk of single gene diseases, using empirical recurrence risks are the most important and available method to evaluate pedigree of complex (multifactorial), chromosomal, and unknown etiology disorders. Although, generally, empirical recurrent risks are not accurate, either because of the difference of gene frequencies and environmental factors among populations or heterogeneity of disease; using results of plenty family population studies, computerized estimating programs, genotyping technologies, and Genome-wide association studies (GWASs) of single nucleotide polymorphisms (SNPs), can make it possible nowadays to estimate these risks. The specific family situation and importance recurrence risks of some common complex genetic diseases will be presented in this review and some important multifactorial disorders’ recurrence risks will be summarized to help genetic counselors for supporting families and representing better view of genetic disorders.
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Affiliation(s)
- Mahdi Bijanzadeh
- Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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At the Heart of the Pregnancy: What Prenatal and Cardiovascular Genetic Counselors Need to Know about Maternal Heart Disease. J Genet Couns 2017; 26:669-688. [DOI: 10.1007/s10897-017-0081-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Accepted: 02/14/2017] [Indexed: 01/25/2023]
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Canobbio MM, Warnes CA, Aboulhosn J, Connolly HM, Khanna A, Koos BJ, Mital S, Rose C, Silversides C, Stout K. Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2017; 135:e50-e87. [PMID: 28082385 DOI: 10.1161/cir.0000000000000458] [Citation(s) in RCA: 260] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Today, most female children born with congenital heart disease will reach childbearing age. For many women with complex congenital heart disease, carrying a pregnancy carries a moderate to high risk for both the mother and her fetus. Many such women, however, do not have access to adult congenital heart disease tertiary centers with experienced reproductive programs. Therefore, it is important that all practitioners who will be managing these women have current information not only on preconception counseling and diagnostic evaluation to determine maternal and fetal risk but also on how to manage them once they are pregnant and when to refer them to a regional center with expertise in pregnancy management.
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Sukenik-Halevy R, Sukenik S, Koifman A, Alpert Y, Hershkovitz R, Levi A, Biron-Shental T. Clinical aspects of prenatally detected congenital heart malformations and the yield of chromosomal microarray analysis. Prenat Diagn 2016; 36:1185-1191. [PMID: 27794172 DOI: 10.1002/pd.4954] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 10/25/2016] [Accepted: 10/26/2016] [Indexed: 12/13/2022]
Abstract
OBJECTIVE The yield of chromosomal microarray analysis (CMA) for prenatally detected congenital heart defects (CHD) is 6.6% to 19.2%. We evaluated the yield of CMA in cases of prenatally detected CHD in regard to specific clinical characteristics. METHODS Data from 192 cases of CHD including type, clinical and familial background, workup performed during the pregnancy, and pregnancy outcomes were collected. RESULTS Fetal echocardiography was performed in all cases; 61.4% of CHD were suspected by ultrasound. There was a positive family history (FH) in 15.7%. Abnormal nuchal translucency or umbilical cord anomalies were detected in 1.7% and 5.9%, respectively, and 55.1% were isolated cases. In 11 of 96 cases in which genetic testing was performed, karyotype and CMA were abnormal (11.5%). The detection rate of CMA (performed in 72 cases) was 9.7%. The yield of CMA was similar in simple cases, isolated cases, and cases with a positive FH. CMA was abnormal in 7.3% of ventricular septal defect cases. CONCLUSION Most cases of prenatally detected CHD had no additional extra-cardiac, sonographic findings suggesting increased risk for CHD. The yield of CMA testing was significant in all clinical scenarios including simple heart malformations, isolated cases, and cases with a positive FH. © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Rivka Sukenik-Halevy
- Department of OBGYN, Meir Medical Center, Kfar Saba, Israel.,Genetics Institute, Meir Medical Center, Kfar Saba, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shay Sukenik
- Ben Gurion University of the Negev, Beer Sheva, Israel
| | - Arie Koifman
- Ben Gurion University of the Negev, Beer Sheva, Israel.,Genetics Institute, Soroka Medical Center, Beer Sheva, Israel
| | - Yoav Alpert
- Department of OBGYN, Meir Medical Center, Kfar Saba, Israel
| | - Reli Hershkovitz
- Ben Gurion University of the Negev, Beer Sheva, Israel.,Ultrasound Unit, Soroka Medical Center, Beer Sheva, Israel
| | - Alex Levi
- Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.,Department of Cardiology, Meir Medical Center, Kfar Saba, Israel
| | - Tal Biron-Shental
- Department of OBGYN, Meir Medical Center, Kfar Saba, Israel.,Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Abstract
Congenital heart disease (CHD) is the most common class of major malformations in humans. The historical association with large chromosomal abnormalities foreshadowed the role of submicroscopic rare copy number variations (CNVs) as important genetic causes of CHD. Recent studies have provided robust evidence for these structural variants as genome-wide contributors to all forms of CHD, including CHD that appears isolated without extra-cardiac features. Overall, a CNV-related molecular diagnosis can be made in up to one in eight patients with CHD. These include de novo and inherited variants at established (chromosome 22q11.2), emerging (chromosome 1q21.1), and novel loci across the genome. Variable expression of rare CNVs provides support for the notion of a genetic spectrum of CHD that crosses traditional anatomic classification boundaries. Clinical genetic testing using genome-wide technologies (e.g., chromosomal microarray analysis) is increasingly employed in prenatal, paediatric and adult settings. CNV discoveries in CHD have translated to changes to clinical management, prognostication and genetic counselling. The convergence of findings at individual gene and at pathway levels is shedding light on the mechanisms that govern human cardiac morphogenesis. These clinical and research advances are helping to inform whole-genome sequencing, the next logical step in delineating the genetic architecture of CHD.
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Sifrim A, Hitz MP, Wilsdon A, Breckpot J, Al Turki SH, Thienpont B, McRae J, Fitzgerald TW, Singh T, Swaminathan GJ, Prigmore E, Rajan D, Abdul-Khaliq H, Banka S, Bauer UMM, Bentham J, Berger F, Bhattacharya S, Bu'Lock F, Canham N, Colgiu IG, Cosgrove C, Cox H, Daehnert I, Daly A, Danesh J, Fryer A, Gewillig M, Hobson E, Hoff K, Homfray T, The INTERVAL Study, Kahlert AK, Ketley A, Kramer HH, Lachlan K, Lampe AK, Louw JJ, Manickara AK, Manase D, McCarthy KP, Metcalfe K, Moore C, Newbury-Ecob R, Omer SO, Ouwehand WH, Park SM, Parker MJ, Pickardt T, Pollard MO, Robert L, Roberts DJ, Sambrook J, Setchfield K, Stiller B, Thornborough C, Toka O, Watkins H, Williams D, Wright M, Mital S, Daubeney PEF, Keavney B, Goodship J, The UK10K Consortium, Abu-Sulaiman RM, Klaassen S, Wright CF, Firth HV, Barrett JC, Devriendt K, FitzPatrick DR, Brook JD, The Deciphering Developmental Disorders Study, Hurles M. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat Genet 2016; 48:1060-5. [PMID: 27479907 PMCID: PMC5988037 DOI: 10.1038/ng.3627] [Citation(s) in RCA: 321] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Accepted: 06/24/2016] [Indexed: 02/02/2023]
Abstract
Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.
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Affiliation(s)
| | - Marc-Phillip Hitz
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
- Department of Congenital Heart Disease and Pediatric Cardiology, UKSH Kiel, Germany
- DZHK (German Center for Cardiovascular Research), partner site Berlin/Hamburg/Kiel/Lübeck, Germany
| | - Anna Wilsdon
- School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, United Kingdom
| | - Jeroen Breckpot
- Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium
| | - Saeed H. Al Turki
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
- Department of Pathology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
- Harvard Medical School Genetics Training Program, Boston, United States of America
| | - Bernard Thienpont
- Vesalius Research Center, VIB, Leuven, Belgium
- Department of Oncology, Laboratory for Translational Genetics, KU Leuven, Leuven, Belgium
| | - Jeremy McRae
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
| | | | | | | | - Elena Prigmore
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
| | - Diana Rajan
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
| | - Hashim Abdul-Khaliq
- Department of Paediatric Cardiology, Saarland University, Homburg, Germany
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
| | - Siddharth Banka
- Manchester Centre for Genomic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom
- Manchester Centre for Genomic Medicine, St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Ulrike M. M. Bauer
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
| | - Jamie Bentham
- Department of Paediatric Cardiology, Yorkshire Heart Centre, Leeds, United Kingdom
| | - Felix Berger
- DZHK (German Center for Cardiovascular Research), partner site Berlin/Hamburg/Kiel/Lübeck, Germany
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
- German Heart Institute Berlin, Charité Universitaetsmedizin Berlin, Department of Congenital Heart Disease and Pediatric Cardiology, Berlin, Germany
| | - Shoumo Bhattacharya
- Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - Frances Bu'Lock
- East Midlands Congenital Heart Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Natalie Canham
- North West Thames Regional Genetics Centre, London North West Healthcare NHS Trust, Harrow, United Kingdom
| | | | - Catherine Cosgrove
- Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - Helen Cox
- West Midlands Regional Genetics Service, Birmingham Women’s NHS Foundation Trust, Birmingham Women’s Hospital, Birmingham, United Kingdom
| | - Ingo Daehnert
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
- Department of Pediatric Cardiology, Heart Center, University of Leipzig, Germany
| | - Allan Daly
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
| | - John Danesh
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
- NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- INTERVAL Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Alan Fryer
- Department of Clinical Genetics, Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, United Kingdom
| | - Marc Gewillig
- Department of Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
| | - Emma Hobson
- Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Department of Clinical Genetics, Chapel Allerton Hospital, Leeds, United Kingdom
| | - Kirstin Hoff
- Department of Congenital Heart Disease and Pediatric Cardiology, UKSH Kiel, Germany
- DZHK (German Center for Cardiovascular Research), partner site Berlin/Hamburg/Kiel/Lübeck, Germany
| | - Tessa Homfray
- South West Thames Regional Genetics Centre, St George’s Healthcare NHS Trust, St George’s, University of London, London, United Kingdom
| | | | - Anne-Karin Kahlert
- Department of Congenital Heart Disease and Pediatric Cardiology, UKSH Kiel, Germany
- DZHK (German Center for Cardiovascular Research), partner site Berlin/Hamburg/Kiel/Lübeck, Germany
- Institute for Clinical Genetics, Carl Gustav Carus Faculty of Medicine, Dresden, Germany
| | - Ami Ketley
- School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, United Kingdom
| | - Hans-Heiner Kramer
- Department of Congenital Heart Disease and Pediatric Cardiology, UKSH Kiel, Germany
- DZHK (German Center for Cardiovascular Research), partner site Berlin/Hamburg/Kiel/Lübeck, Germany
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
| | - Katherine Lachlan
- Wessex Clinical Genetics Service, University Hospital Southampton, Princess Anne Hospital, Southampton, United Kingdom
- Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury District Hospital, Salisbury, United Kingdom
- Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Anne Katrin Lampe
- South East of Scotland Clinical Genetic Service, IGMM North, Western General Hospital, Edinburgh, United Kingdom
| | - Jacoba J. Louw
- Department of Pediatric Cardiology, University Hospitals Leuven, Leuven, Belgium
| | | | | | - Karen P. McCarthy
- Cardiac Morphology Unit, Royal Brompton Hospital and the National Heart and Lung Institute, Imperial College, United Kingdom
| | - Kay Metcalfe
- Manchester Centre for Genomic Medicine, St Mary’s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Carmel Moore
- INTERVAL Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
| | - Ruth Newbury-Ecob
- Department of Clinical Genetics, St Michael's Hospital, Bristol, United Kingdom
| | - Seham Osman Omer
- Division of Pediatric Cardiology, King Abdulaziz Cardiac Center, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
| | - Willem H. Ouwehand
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
- NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- Department of Haematology, University of Cambridge, Long Road, Cambridge, United Kingdom
- NHS Blood and Transplant, Long Road, Cambridge, United Kingdom
| | - Soo-Mi Park
- East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom
| | - Michael J. Parker
- Sheffield Children’s Hospital NHS Foundation Trust, Western Bank, Sheffield
| | - Thomas Pickardt
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
| | | | - Leema Robert
- South East Thames Regional Genetics Centre, Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, United Kingdom
| | - David J. Roberts
- NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- NHS Blood and Transplant, John Radcliffe Hospital, Oxford, United Kingdom
- Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
| | - Jennifer Sambrook
- INTERVAL Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
- Department of Haematology, University of Cambridge, Long Road, Cambridge, United Kingdom
| | - Kerry Setchfield
- School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, United Kingdom
| | - Brigitte Stiller
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
- Department of Congenital Heart Defects and Paediatric Cardiology, Heart Centre, University of Freiburg, Germany
| | - Chris Thornborough
- East Midlands Congenital Heart Centre, Glenfield Hospital, Leicester, United Kingdom
| | - Okan Toka
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
- Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Pediatric Cardiology, Erlangen, Germany
| | - Hugh Watkins
- Department of Cardiovascular Medicine, University of Oxford, Oxford, United Kingdom
| | - Denise Williams
- West Midlands Regional Genetics Service, Birmingham Women’s NHS Foundation Trust, Birmingham Women’s Hospital, Birmingham, United Kingdom
| | - Michael Wright
- Northern Genetics Service, Newcastle upon Tyne Hospitals NHS Foundation Trust, Institute of Human Genetics, International Centre for Life, Newcastle upon Tyne, United Kingdom
| | | | - Piers E. F. Daubeney
- Division of Paediatric Cardiology, Royal Brompton Hospital, London, United Kingdom
- Paediatric Cardiology, Imperial College, London, United Kingdom
| | - Bernard Keavney
- Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom
| | - Judith Goodship
- Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom
| | | | - Riyadh Mahdi Abu-Sulaiman
- Division of Pediatric Cardiology, King Abdulaziz Cardiac Center, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
- King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
- King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia
| | - Sabine Klaassen
- DZHK (German Center for Cardiovascular Research), partner site Berlin/Hamburg/Kiel/Lübeck, Germany
- Competence Network for Congenital Heart Defects, National Register for Congenital Heart Defects, DZHK (German Center for Cardiovascular Research), Germany
- Experimental and Clinical Research Center (ECRC), Charité Medical Faculty and Max-Delbruck-Center for Molecular Medicine, Berlin, Germany
- Department of Pediatric Cardiology, Charité University Medicine, Berlin, Germany
| | | | - Helen V. Firth
- East Anglian Medical Genetics, Cambridge University Hospitals NHS Foundation Trust, Biomedical Campus, Cambridge, United Kingdom
| | | | | | - David R. FitzPatrick
- Medical Research Council (MRC) Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine (IGMM), University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
| | - J. David Brook
- School of Life Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, United Kingdom
| | | | - Matthew Hurles
- Wellcome Trust Sanger Institute, Cambridge, United Kingdom
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Landis BJ, Ware SM. The Current Landscape of Genetic Testing in Cardiovascular Malformations: Opportunities and Challenges. Front Cardiovasc Med 2016; 3:22. [PMID: 27504451 PMCID: PMC4959014 DOI: 10.3389/fcvm.2016.00022] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 06/30/2016] [Indexed: 12/21/2022] Open
Abstract
Human cardiovascular malformations (CVMs) frequently have a genetic contribution. Through the application of novel technologies, such as next-generation sequencing, DNA sequence variants associated with CVMs are being identified at a rapid pace. While clinicians are now able to offer testing with NGS gene panels or whole exome sequencing to any patient with a CVM, the interpretation of genetic variation remains problematic. Variable phenotypic expression, reduced penetrance, inconsistent phenotyping methods, and the lack of high-throughput functional testing of variants contribute to these challenges. This article elaborates critical issues that impact the decision to broadly implement clinical molecular genetic testing in CVMs. Major benefits of testing include establishing a genetic diagnosis, facilitating cost-effective screening of family members who may have subclinical disease, predicting recurrence risk in offsprings, enabling early diagnosis and anticipatory management of CV and non-CV disease phenotypes, predicting long-term outcomes, and facilitating the development of novel therapies aimed at disease improvement or prevention. Limitations include financial cost, psychosocial cost, and ambiguity of interpretation of results. Multiplex families and patients with syndromic features are two groups where disease causation could potentially be firmly established. However, these account for the minority of the overall CVM population, and there is increasing recognition that genotypes previously associated with syndromes also exist in patients who lack non-CV findings. In all circumstances, ongoing dialog between cardiologists and clinical geneticists will be needed to accurately interpret genetic testing and improve these patients’ health. This may be most effectively implemented by the creation and support of CV genetics services at centers committed to pursuing testing for patients.
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Affiliation(s)
- Benjamin J Landis
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Stephanie M Ware
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA
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Burnicka-Turek O, Steimle JD, Huang W, Felker L, Kamp A, Kweon J, Peterson M, Reeves RH, Maslen CL, Gruber PJ, Yang XH, Shendure J, Moskowitz IP. Cilia gene mutations cause atrioventricular septal defects by multiple mechanisms. Hum Mol Genet 2016; 25:3011-3028. [PMID: 27340223 DOI: 10.1093/hmg/ddw155] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 05/13/2016] [Accepted: 05/18/2016] [Indexed: 01/13/2023] Open
Abstract
Atrioventricular septal defects (AVSDs) are a common severe form of congenital heart disease (CHD). In this study we identified deleterious non-synonymous mutations in two cilia genes, Dnah11 and Mks1, in independent N-ethyl-N-nitrosourea-induced mouse mutant lines with heritable recessive AVSDs by whole-exome sequencing. Cilia are required for left/right body axis determination and second heart field (SHF) Hedgehog (Hh) signaling, and we find that cilia mutations affect these requirements differentially. Dnah11avc4 did not disrupt SHF Hh signaling and caused AVSDs only concurrently with heterotaxy, a left/right axis abnormality. In contrast, Mks1avc6 disrupted SHF Hh signaling and caused AVSDs without heterotaxy. We performed unbiased whole-genome SHF transcriptional profiling and found that cilia motility genes were not expressed in the SHF whereas cilia structural and signaling genes were highly expressed. SHF cilia gene expression predicted the phenotypic concordance between AVSDs and heterotaxy in mice and humans with cilia gene mutations. A two-step model of cilia action accurately predicted the AVSD/heterotaxyu phenotypic expression pattern caused by cilia gene mutations. We speculate that cilia gene mutations contribute to both syndromic and non-syndromic AVSDs in humans and provide a model that predicts the phenotypic consequences of specific cilia gene mutations.
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Affiliation(s)
- Ozanna Burnicka-Turek
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA,
| | - Jeffrey D Steimle
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA
| | - Wenhui Huang
- Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
| | - Lindsay Felker
- Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
| | - Anna Kamp
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA
| | - Junghun Kweon
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA
| | - Michael Peterson
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA
| | - Roger H Reeves
- Department of Physiology and Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Cheryl L Maslen
- Knight Cardiovascular Institute and Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239, USA and
| | - Peter J Gruber
- Department of Cardiothoracic Surgery, University of Iowa, Iowa City, IA 52245, USA
| | - Xinan H Yang
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA
| | - Jay Shendure
- Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
| | - Ivan P Moskowitz
- Departments of Pediatrics, Pathology, and Human Genetics, The University of Chicago, Chicago, IL 60637, USA,
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Helm BM, Freeze SL. Genetic Evaluation and Use of Chromosome Microarray in Patients with Isolated Heart Defects: Benefits and Challenges of a New Model in Cardiovascular Care. Front Cardiovasc Med 2016; 3:19. [PMID: 27379245 PMCID: PMC4905945 DOI: 10.3389/fcvm.2016.00019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 05/30/2016] [Indexed: 01/26/2023] Open
Abstract
Congenital heart defects (CHDs) are common birth defects and result in significant morbidity and global economic impact. Genetic factors play a role in most CHDs; however, identification of these factors has been historically slow due to technological limitations and incomplete understanding of the impact of human genomic variation on normal and abnormal cardiovascular development. The advent of chromosome microarray (CMA) brought tremendous gains in identifying chromosome abnormalities in a variety of human disorders and is now considered part of a standard evaluation for individuals with multiple congenital anomalies and/or neurodevelopmental disorders. Several studies investigating use of CMA found that this technology can identify pathogenic copy-number variations (CNVs) in up to 15-20% of patients with CHDs with other congenital anomalies. However, there have been fewer studies exploring the use of CMA for patients with isolated CHDs. Recent studies have shown that the diagnostic yield of CMA in individuals with seemingly isolated CHD is lower than in individuals with CHDs and additional anomalies. Nevertheless, positive CMA testing in this group supports chromosome variation as one mechanism underlying the development of isolated, non-syndromic CHD - either as a causative or risk-influencing genetic factor. CMA has also identified novel genomic variation in CHDs, shedding light on candidate genes and pathways involved in cardiac development and malformations. Additional studies are needed to further address this issue. Early genetic diagnosis can enhance the medical management of patients and potentially provide crucial information about recurrence. This information is critical for genetic counseling of patients and family members. In this review, we review CMA for the non-genetics cardiology provider, offer a summary of CNV in isolated CHDs, and advocate for the use of CMA as part of the cardiovascular genetics evaluation of patients with isolated CHDs. We also provide perspective regarding the benefits and challenges that lie ahead for this model in the clinical setting.
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Affiliation(s)
- Benjamin M Helm
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, IU Health , Indianapolis, IN , USA
| | - Samantha L Freeze
- Department of Pediatrics, Indiana University School of Medicine, IU Health , Indianapolis, IN , USA
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47
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Genetics of Hypoplastic Left Heart Syndrome. J Pediatr 2016; 173:25-31. [PMID: 26996724 DOI: 10.1016/j.jpeds.2016.02.052] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 01/25/2016] [Accepted: 02/19/2016] [Indexed: 12/13/2022]
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Hebson C, Saraf A, Book WM. Risk Assessment and Management of the Mother with Cardiovascular Disease. Clin Perinatol 2016; 43:1-22. [PMID: 26876118 DOI: 10.1016/j.clp.2015.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Chronic medical conditions account for most nonobstetrical pregnancy-related maternal complications. Preconception counseling of women with cardiovascular disease can be aided by an understanding of cardiovascular physiology in pregnancy and risk scores to guide management.
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Affiliation(s)
- Camden Hebson
- Department of Medicine, The Sibley Heart Center, Emory University School of Medicine, 1365 Clifton Road Northeast, Clinic A, 2nd Floor, Cardiology, Atlanta, GA 30322, USA; Department of Pediatrics, The Sibley Heart Center, Emory University School of Medicine, 1365 Clifton Road Northeast, Clinic A, 2nd Floor, Cardiology, Atlanta, GA 30322, USA
| | - Anita Saraf
- Division of Cardiology, Department of Medicine, Emory University School of Medicine, 1365 Clifton Road Northeast, Atlanta, GA 30322, USA
| | - Wendy M Book
- Division of Cardiology, Department of Medicine, Emory Adult Congenital Heart Center, Emory University School of Medicine, 1365 Clifton Road Northeast, Clinic A, 2nd Floor, Cardiology, Atlanta, GA 30322, USA.
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49
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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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50
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Kang G, Xiao J, Wang J, Chen J, Li W, Wang Y, Liu Q, Wang Z, Xia J, Huang J, Cheng L, Chen Y, Chen Q, Yang F. Congenital Heart Disease in Local and Migrant Elementary Schoolchildren in Dongguan, China. Am J Cardiol 2016; 117:461-4. [PMID: 26704031 DOI: 10.1016/j.amjcard.2015.10.061] [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: 07/22/2015] [Revised: 10/30/2015] [Accepted: 10/30/2015] [Indexed: 12/18/2022]
Abstract
The aim of this study was to determine the prevalence and treated status of congenital heart disease (CHD) in elementary schoolchildren and facilitate the long-term planning of health care, resource allocation, and development of targeted primary prevention strategies. From November 2011 to November 2012, 540,574 schoolchildren from 449 elementary schools were screened for CHD by trained doctors in Dongguan City. The schoolchildren who were suspected to have CHD were referred to a pediatric cardiologist and/or an echocardiographist for complete evaluation. Of them, 214,634 (39.7%) were local children and 325,940 (60.3%) were migrant children. The total prevalence of CHD was 2.14‰, and there was a significant difference (p <0.05) of the CHD prevalence between local (1.97‰) and migrant children (2.26‰). The treatment rates of CHD in local children and in migrant children were 63.51% and 47.21%, respectively (p <0.01). The commonest CHD was ventricular septal defect (43.13%), followed by atrial septal defect (25.84%) and patent ductus arteriosus (12.79%). With respect to gender, CHD was equally distributed between men and women. In conclusion, social, economic, and environmental risk factors that affect health of migrant children with CHD call for more attention from health policy makers and researchers in contemporary China. Efforts should be made to increase public health investment, establish health care manage system for children from migrant families, and increase the parents' awareness of preventing the CHD.
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Affiliation(s)
- Guanyang Kang
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China; Medical College of Shantou University, Guangdong, China
| | - Jianmin Xiao
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China.
| | - Jieying Wang
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Jiuhao Chen
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Wei Li
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Yitong Wang
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Qingchun Liu
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Zhiming Wang
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Jinxi Xia
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Jianzhong Huang
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Ling Cheng
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Yuqiang Chen
- Medical College of Shantou University, Guangdong, China
| | - Qiaozhu Chen
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
| | - Fan Yang
- Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China
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