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1. Percentage Predicted Peak Oxygen Consumption in People With Fontan Circulation: A Rapid Systematic Scoping Review and Validation Study

Author: Curtis A. Wadey, Owen W. Tomlinson, Alan R. Barker, A. Graham Stuart, Derek L. Tran, Karina Laohachai, Julian Ayer, Robert G. Weintraub, Rachael Cordina, and Craig A. Williams
Subjects: cardiorespiratory fitness, congenital heart disease, CPET, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background Peak oxygen consumption (peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$) is routinely measured in people who have congenital heart disease and is reported as a percentage of predicted value, based upon age‐ and sex‐matched normative reference values (NRVs). This study aimed to identify which NRVs are being used, assess whether NRVs are being applied appropriately, and evaluate if recommended NRVs are valid when applied to people with congenital heart disease. Methods and Results A systematic scoping review identified studies that reported peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ percentage of predicted value in people with congenital heart disease. A modified risk of bias tool evaluated the included studies. Forty‐five studies reported peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ percentage of predicted value, and only 21 (47%) studies described or provided a reference on how their percentage of predicted value was calculated. The most cited NRVs were from Wasserman (n=12) and Cooper and Weiler‐Ravell (n=7). Risk of bias analysis judged 63% of studies as having some concerns. The NRVs recommended by the American Heart Association were applied to participants with a Fontan circulation (n=70; aged 26.5±6.4 years; 59% women) to examine validity. Predicted peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ values from the Wasserman NRV was not significantly associated to measured peak V̇O2$$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ values (men: b=0.31, R2≤0.01; women: b=0.07, R2=0.02). Conclusions Numerous NRVs have been applied to individuals with congenital heart disease and are often poorly reported and inappropriately matched to participants. The Wasserman NRV was the most cited but showed poor validity when applied to a Fontan cohort.
Published: 2024
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2. The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death

Author: Emma S. Singer, Joshua Crowe, Mira Holliday, Julia C. Isbister, Sean Lal, Natalie Nowak, Laura Yeates, Charlotte Burns, Sulekha Rajagopalan, Ivan Macciocca, Ingrid King, Julie Wacker, Jodie Ingles, Robert G. Weintraub, Christopher Semsarian, and Richard D. Bagnall
Subjects: Medicine, Genetics, QH426-470
Abstract: Abstract There is an incomplete understanding of the burden of splice-disrupting variants in definitively associated inherited heart disease genes and whether these genes can amplify from blood RNA to support functional confirmation of splicing outcomes. We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue. Variants were functionally assessed and classified for pathogenicity. We found 88 in silico-predicted splice-disrupting variants in 128 out of 1242 (10.3%) unrelated participants. There was an excess burden of splice-disrupting variants in PKP2 (5.9%), FLNC (2.7%), TTN (2.8%), MYBPC3 (8.2%) and MYH7 (1.3%), in distinct cardiomyopathy subtypes, and KCNQ1 (3.6%) in long QT syndrome. Blood RNA supported the amplification of 21 out of 31 definitive disease-associated inherited heart disease genes. Our functional studies confirmed altered splicing in six variants. Eleven variants of uncertain significance were reclassified as likely pathogenic based on functional studies and six were used for cascade genetic testing in 12 family members. Our study highlights that splice-disrupting variants are a significant cause of inherited heart disease, and that analysis of blood RNA confirms splicing outcomes and supports variant pathogenicity classification.
Published: 2023
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3. A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship

Author: Rachel Austin, Jaye S. Brown, Sarah Casauria, Evanthia O. Madelli, Tessa Mattiske, Tiffany Boughtwood, Alejandro Metke, Andrew Davis, Ari E. Horton, David Winlaw, Debjani Das, Magdalena Soka, Eleni Giannoulatou, Emma M. Rath, Eric Haan, Gillian M. Blue, Jitendra Vohra, John J. Atherton, Karin van Spaendonck-Zwarts, Kathy Cox, Leslie Burnett, Mathew Wallis, Matilda Haas, Michael C.J. Quinn, Nicholas Pachter, Nicola K. Poplawski, Zornitza Stark, Richard D. Bagnall, Robert G. Weintraub, Sarah-Jane Pantaleo, Sebastian Lunke, Paul De Fazio, Tina Thompson, Paul James, Yuchen Chang, Diane Fatkin, Ivan Macciocca, Jodie Ingles, Sally L. Dunwoodie, Chris Semsarian, Julie McGaughran, Lesley Ades, Annabel Enriquez, Alison McLean, Renee Smyth, Dimithu Alankarage, James McNamara, Morgan almog, Vanessa Fear, Caroline Medi, Mohammad Al-Shinnag, Miriam Fine, Raymond Sy, Keri Finlay, Di Milnes, Dotti Tang, Denisse Garza, Michael Milward, Jessica Taylor, Ansley Morrish, Shelby Taylor, Chris Barnett, Laura Gongolidis, Jim Morwood, Michel Tchan, Belinda Gray, Helen Mountain, Simon Bodek, Cassie Greer, David Mowat, Jordan Thorpe, Kirsten Boggs, Chai-Ann Ng, Alison Trainer, Michael Bogwitz, Mathilda Haas, Natalie Nowak, Gunjan Trivedi, Bernadette Hanna, Noelia Nunez Martinez, Giulia Valente, Alessandra Bray, Richard Harvey, Monique Ohanian, Marie-Jo Brion, Janette Hayward, Sinead O’Sullivan, Jamie Vandenberg, Jaye Brown, Carmen Herrera, Angela Overkov, Kunal Verma, Rob Bryson Richardson, Adam Hill, Miranda Vidgen, Georgie Hollingsworth, Chirag Patel, Charlotte Burns, Georgina Hollway, Mark Perrin, Kathryn Waddel-Smith, Michelle Cao, Matthew Perry, Will Carr, Denise Howting, Andreas Pflaumer, Peta Phillips, Meredith Wilson, Heather Chalinor, Joanne Isbister, Thuan Phuong, Matilda Jackson, Rachel Pope-Couston, Lisa Worgan, Gavin Chapman, Linda Wornham, Theosodia Charitou, Sarah Jane-Pantaleo, Preeti Punni, Kathy Wu, Belinda Chong, Renee Johnson, Laura Yeates, Felicity Collins, Andrew Kelly, Michael Quinn, Dominica Zentner, Gemma Correnti, Sarah King-Smith, Sulekha Rajagopalan, Edwin Kirk, Hariharan Raju, Fiona Cunningham, Sarah Kummerfeld, Timo Lassman, Matthew Regan, Jason Davis, Jonathon Lipton, Jonathan Rogers, Mark Ryan, Sarah Sandaradura, Michelle de Silva, Paul MacIntyre, Nicole Schonrock, Nicola Den Elzen, Paul Scuffham, Sophie Devery, Amali Mallawaarachchi, Julia Dobbins, Julia Mansour, Isabella Sherburn, Ellenore Martin, Mary-Clare Sherlock, Nathan Dwyer, Jacob Mathew, Emma Singer, Stefanie Elbracht-Leong, Carla Smerdon, David Elliott, and Janine Smith
Subjects: Australian Genomics, Cardiovascular genetic disorders, Genome sequencing, Specialized multidisciplinary care, Genetics, QH426-470, Medicine
Abstract: Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD). Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS. The Flagship adopted a tiered approach to GS analysis. Tier 1 analysis assessed genes with established clinical validity for each cardiovascular condition. Tier 2 analysis assessed lesser-evidenced research-based genes. Tier 3 analysis assessed the functional impact of VUS that remained after tier 1 and tier 2 analysis. Results: Overall, a pathogenic or likely pathogenic variant was identified in 41% of participants with a cardiomyopathy, 40% with an arrhythmia syndrome, and 15% with a familial CHD/CHD+Extra Cardiac Anomalies. A VUS outcome ranged from 13% for arrhythmias to 34% for CHD/CHD+Extra Cardiac Anomalies participants. Tier 2 research analysis identified a likely pathogenic/pathogenic variant for a further 15 participants and a VUS for an additional 15 participants. Conclusion: The Flagship successfully facilitated a model of care that harnesses clinical GS and functional genomics for the resolution of VUS in the clinical setting. This valuable data set can be used to inform clinical practice and facilitate research into the future.
Published: 2024
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4. Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy

Author: Robert Lesurf, Abdelrahman Said, Oyediran Akinrinade, Jeroen Breckpot, Kathleen Delfosse, Ting Liu, Roderick Yao, Gabrielle Persad, Fintan McKenna, Ramil R. Noche, Winona Oliveros, Kaia Mattioli, Shreya Shah, Anastasia Miron, Qian Yang, Guoliang Meng, Michelle Chan Seng Yue, Wilson W. L. Sung, Bhooma Thiruvahindrapuram, Jane Lougheed, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John Smythe, Shashank Jayappa, Vinay J. Rao, Jayaprakash Shenthar, Perundurai S. Dhandapany, Christopher Semsarian, Robert G. Weintraub, Richard D. Bagnall, Jodie Ingles, Genomics England Research Consortium, Marta Melé, Philipp G. Maass, James Ellis, Stephen W. Scherer, and Seema Mital
Subjects: Medicine, Genetics, QH426-470
Abstract: Abstract Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10−7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP.
Published: 2022
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5. Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy

Author: Aine Lynch, Mark Tatangelo, Sachin Ahuja, Chun-Po Steve Fan, Sandar Min, Myriam Lafreniere-Roula, Tanya Papaz, Vivian Zhou, Kathryn Armstrong, Peter F. Aziz, Lee N. Benson, Ryan Butts, Andreea Dragulescu, Letizia Gardin, Justin Godown, Aamir Jeewa, Paul F. Kantor, Beth D. Kaufman, Ashwin K. Lal, John J. Parent, Marc Richmond, Mark W. Russell, Seshadri Balaji, Elizabeth A. Stephenson, Chet Villa, John L. Jefferies, Robert Whitehill, Jennifer Conway, Taylor S. Howard, Stephanie J. Nakano, Joseph Rossano, Robert G. Weintraub, and Seema Mital
Subjects: Cardiology and Cardiovascular Medicine
Published: 2023

6. Long-term Outcomes of Staged Complete Repair of Pulmonary Atresia With Ventricular Septal Defect

Author: Samuel J. Macalister, Edward Buratto, Phillip S. Naimo, Xin Tao Ye, Nicholas Fulkoski, Robert G. Weintraub, Christian P. Brizard, and Igor E. Konstantinov
Subjects: Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract: The optimal strategy for pulmonary atresia with ventricular septal defect (PA/VSD) without major aortopulmonary collateral arteries (MAPCAs) is yet to be defined. It remains unclear how primary complete repair compares with staged repair.We reviewed the records of 107 patients with PA/VSD managed with systemic-to-pulmonary shunts from February 1989 to November 2019. Tables presenting summary statistics of patient and surgical data and Kaplan-Meier curves presenting repair, mortality and reoperation were created. Logistic regression analysis was performed to identify risk factors for repair, morbidity and mortality.Ninety-one (85%) patients achieved complete repair at a median age of 1 year (interquartile range [IQR] 8-20 months). Survival was 97 (90%) patients at 6 months, 91 (85%) at 20 months and 87 (81%) at 10 years. Shunt diameter of 3.5 mm or less (p = 0.006) and shunt after 2009 (p0.001) were associated with earlier progression to complete repair. Shunt diameter of 3.5 mm or less was an independent risk factor for interstage morbidity (hazard ratio 4.5 [IQR 1.1-18.5], p = 0.039), but was not associated with complete repair (p = 0.75) or mortality (p = 0.62). The median follow-up period was 10.5 years (IQR 3.6-18.8 years) from birth.The complete repair and long-term survival rates of staged PA/VSD repair are high. The use of smaller shunts has resulted in earlier complete repair and is associated with increased risk of morbidity but not mortality.
Published: 2023

7. Outcomes of the arterial switch operation in patients with inverted coronary artery anatomy

Author: Tyson A, Fricke, Edward, Buratto, Kaushik, Thungathurthi, Antonia, Schulz, Robert G, Weintraub, Christian P, Brizard, and Igor E, Konstantinov
Subjects: Arterial Switch Operation, Pulmonary and Respiratory Medicine, Treatment Outcome, Transposition of Great Vessels, Coronary Vessel Anomalies, Humans, Surgery, Cardiology and Cardiovascular Medicine, Coronary Vessels, Retrospective Studies
Abstract: Patients undergoing the arterial switch operation (ASO) with inverted coronary anatomy represent a technical challenge. We sought to determine the long-term outcomes of patients with inverted coronary anatomy who underwent an ASO.A retrospective analysis of patients who underwent an ASO with inverted coronary anatomy at a single institution was performed and comparison was made between patients with inverted and normal coronary anatomy.There were 43 (5.1% [43 out of 844]) patients with inverted coronary anatomy. Twenty patients (46.5% [20 out of 43]) had a right coronary artery that arises from sinus 1 and the left anterior descending and circumflex coronaries arise from sinus 2 anatomy and 23 (53.5% [23 out of 43]) patients with right coronary artery that arises from sinus 1 and gives rise to the left anterior descending with the circumflex coronaries arising from sinus 2. Median follow-up was 17 years (interquartile range, 12-21 years). Overall early mortality was 7.0% (3 out of 43) compared with 3.1% (17 out of 556) in patients with normal coronary anatomy undergoing operation over the same time period (P = .17). There were 2 (10% [2 out of 20]) early deaths in the right coronary artery that arises from sinus 1 and gives rise to the left anterior descending with the circumflex coronaries arising from sinus 2 group and 1 (4.3% [1 out of 23]) early death in the right coronary artery that arises from sinus 1 and the left anterior descending and circumflex coronaries arise from sinus 2 group. There was 1 late death occurring at 40 days after ASO. Nine (23% [9 out of 39]) patients had 15 reinterventions occurring at median 3.6 years (interquartile range, 1.1-8.2 years). The most common cause of reintervention was main or branch pulmonary artery stenosis (15% [6 out of 39]). Freedom from reintervention was 78% (95% CI, 68%-93%) and 75% (95% CI, 56%-86%) at 10 and 15 years, respectively. At final follow-up, all surviving local patients except 1 was in New York Heart Association functional class I.Patients with inverted coronary anatomy who underwent an ASO had a higher mortality but this was not statistically significant. However, there were no coronary reinterventions in survivors.
Published: 2022

8. Long-term outcomes of the arterial switch operation

Author: Yves d'Udekem, Igor E. Konstantinov, Edward Buratto, Christian P. Brizard, Andrew Bullock, Robert G. Weintraub, Leeanne Grigg, Tyson A. Fricke, Patrick Disney, and Gavin R. Wheaton
Subjects: Adult, Heart Septal Defects, Ventricular, Male, Reoperation, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Transposition of Great Vessels, Aortic Valve Insufficiency, Long Term Adverse Effects, Ventricular Function, Left, Postoperative Complications, Older patients, Interquartile range, Internal medicine, medicine.artery, Outcome Assessment, Health Care, Long term outcomes, Humans, Medicine, Retrospective Studies, business.industry, Hazard ratio, Australia, Infant, Newborn, Neoaortic root, Confidence interval, Arterial Switch Operation, Aortic Valve, Pulmonary artery, Cardiology, Neoaortic valve regurgitation, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Objectives The arterial switch operation (ASO) has excellent early outcomes in the modern era. We sought to determine the long-term outcomes in patients who underwent an ASO at a single institution. Methods Patients who underwent an ASO between 1983 and 2015 were identified from the hospital database and retrospectively reviewed using hospital records. Results From 1983 to 2015, 844 patients with a biventricular circulation underwent an ASO. There were 28 (3.3%, 28/844) early deaths. Follow-up was available for 94% (729/774) of local patients after hospital discharge. Median follow-up was 15 years (interquartile range, 8-20 years). There were 187 (26%, 187/729) patients with more than 20 years of follow-up and 95 (13%, 95/729) patients with more than 25 years of follow-up. Overall survival was 95% (95% confidence interval [CI], 94%-97%) at 10 and 25 years after the ASO. At 25 years after ASO, freedom from overall reintervention was 77% (95% CI, 73%-81%), freedom from reoperation on the neoaortic root or neoaortic valve was 92% (95% CI, 88%-95%), and freedom from coronary reoperation was 99% (95% CI, 98%-99.7%). Left ventricular (LV) systolic function was normal in 595 of 609 (98%) of patients who had LV function quantified at latest follow-up. Of the 95 patients with more than 25 years of follow-up after ASO, 6 (6.3%) had at least moderate neoaortic valve regurgitation (AR) and 8 (8.4%) had undergone replacement of the neoaortic valve. Conclusions Overall, survivors of ASO have excellent late survival and normal LV systolic function into adult life. However, AR and reoperation on the neoaortic valve remains an issue for older patients.
Published: 2022

9. Genetic Basis of Childhood Cardiomyopathy

Author: Richard D. Bagnall, Emma S. Singer, Julie Wacker, Natalie Nowak, Jodie Ingles, Ingrid King, Ivan Macciocca, Joshua Crowe, Anne Ronan, Robert G. Weintraub, and Christopher Semsarian
Subjects: Adult, Cardiomyopathy, Dilated, Pulmonary and Respiratory Medicine, Heart Diseases, Humans, Genetic Testing, General Medicine, Cardiomyopathy, Hypertrophic, Child, Cardiomyopathies, Cardiology and Cardiovascular Medicine
Abstract: Background: The causes of cardiomyopathy in children are less well described than in adults. We evaluated the clinical diagnoses and genetic causes of childhood cardiomyopathy and outcomes of cascade genetic testing in family members. Methods: We recruited children from a pediatric cardiology service or genetic heart diseases clinic. We performed Sanger, gene panel, exome or genome sequencing and classified variants for pathogenicity using American College of Molecular Genetics and Genomics guidelines. Results: Cardiomyopathy was diagnosed in 221 unrelated children aged ≤18 years. Children mostly had hypertrophic cardiomyopathy (n=98, 44%) or dilated cardiomyopathy (n=89, 40%). The highest genetic testing diagnostic yields were in restrictive cardiomyopathy (n=16, 80%) and hypertrophic cardiomyopathy (n=65, 66%), and lowest in dilated cardiomyopathy (n=26, 29%) and left ventricular noncompaction (n=3, 25%). Pathogenic variants were primarily found in genes encoding sarcomere proteins, with TNNT2 and TNNI3 variants associated with more severe clinical outcomes. Ten children (4.5%) had multiple pathogenic variants. Genetic test results prompted review of clinical diagnosis in 14 families with syndromic, mitochondrial or metabolic gene variants. Cascade genetic testing in 127 families confirmed 24 de novo variants, recessive inheritance in 8 families, and supported reclassification of 12 variants. Conclusions: Genetic testing of children with cardiomyopathy supports a precise clinical diagnosis, which may inform prognosis.
Published: 2022

10. Defining the Fetal Gene Program at Single-Cell Resolution in Pediatric Dilated Cardiomyopathy

Author: Neda R. Mehdiabadi, Choon Boon Sim, Belinda Phipson, Ravi K.R. Kalathur, Yuliangzi Sun, Celine J. Vivien, Menno ter Huurne, Adam T. Piers, James E. Hudson, Alicia Oshlack, Robert G. Weintraub, Igor E. Konstantinov, Nathan J. Palpant, David A. Elliott, and Enzo R. Porrello
Subjects: Cardiomyopathy, Dilated, Fetus, Physiology (medical), Humans, Cardiology and Cardiovascular Medicine, Child
Published: 2022

11. Characterization of clinically relevant copy-number variants from exomes of patients with inherited heart disease and unexplained sudden cardiac death

Author: J. Skinner, Robert G. Weintraub, Emma S. Singer, Samantha Barratt Ross, Christopher Semsarian, Richard D. Bagnall, and Jodie Ingles
Subjects: Genetics, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, medicine.diagnostic_test, Breakpoint, Non-allelic homologous recombination, Biology, Human genetics, mental disorders, medicine, Medical genetics, Copy-number variation, Exome, Genetics (clinical), Exome sequencing, Genetic testing
Abstract: Copy-number variant (CNV) analysis is increasingly performed in genetic diagnostics. We leveraged recent gene curation efforts and technical standards for interpretation and reporting of CNVs to characterize clinically relevant CNVs in patients with inherited heart disease and sudden cardiac death. Exome sequencing data were analyzed for CNVs using eXome-Hidden Markov Model tool in 48 established disease genes. CNV breakpoint junctions were characterized. CNVs were classified using the American College of Medical Genetics and Genomics technical standards. We identified eight CNVs in 690 unrelated probands (1.2%). Characterization of breakpoint junctions revealed nonhomologous end joining was responsible for four deletions, whereas one duplication was caused by nonallelic homologous recombination between duplicated sequences in MYH6 and MYH7. Identifying the precise breakpoint junctions determined the genomic involvement and proved useful for interpreting the clinical relevance of CNVs. Three large deletions involving TTN, MYBPC3, and KCNH2 were classified as pathogenic in three patients. Haplotype analysis of a deletion in ACTN2, found in two families, suggests the deletion was caused by an ancestral event. CNVs infrequently cause inherited heart diseases and should be investigated when standard genetic testing does not reveal a genetic diagnosis.
Published: 2021

12. Long-term Outcomes of Transatrial-Transpulmonary Repair of Tetralogy of Fallot With Anomalous Coronary Arteries

Author: Xin Tao Ye, Edward Buratto, Shuta Ishigami, Robert G. Weintraub, Christian P. Brizard, and Igor E. Konstantinov
Subjects: Pulmonary and Respiratory Medicine, Surgery, General Medicine, Cardiology and Cardiovascular Medicine
Abstract: Repair of tetralogy of Fallot (TOF) can be complicated by the presence of an anomalous coronary artery (ACA) crossing the right ventricular outflow tract (RVOT). This study sought to evaluate the late outcomes of a policy of transatrial-transpulmonary repair for this condition. The transatrial-transpulmonary approach was used in 864 consecutive TOF repairs between 1993 and 2018 at a single institution, of which 55 (6%) patients had an ACA. Nineteen (35%,19/55) patients underwent prior palliation. Late survival and freedom from reoperations were compared with the general cohort of 809 patients who underwent complete repair during the same period. Early mortality was 2% (1/55). Median follow-up was 15.6 years. Late mortality was 6% (3/54). Absence of a preoperative diagnosis of ACA was not a risk factor for worse outcomes in terms of late re-interventions, acute coronary syndrome, residual RVOT gradient, and late mortality. Survival was 91% (95% confidence interval [CI]: 77-96%) at 20 years and was comparable to the general TOF cohort (95%, 95% CI: 90-98%, P = 0.12). Actuarial freedom from any re-intervention was 46% (95% CI: 27-62%) at 20 years, which was also comparable to the general cohort (31%, 95% CI: 20-42%, P = 0.19). The presence of an ACA does not appear to affect late survival or re-intervention rates in patients undergoing transatrial-transpulmonary repair of TOF.
Published: 2022

13. Whole genome sequencing delineates regulatory, copy number, and cryptic splice variants in early onset cardiomyopathy

Author: Robert, Lesurf, Abdelrahman, Said, Oyediran, Akinrinade, Jeroen, Breckpot, Kathleen, Delfosse, Ting, Liu, Roderick, Yao, Gabrielle, Persad, Fintan, McKenna, Ramil R, Noche, Winona, Oliveros, Kaia, Mattioli, Shreya, Shah, Anastasia, Miron, Qian, Yang, Guoliang, Meng, Michelle Chan Seng, Yue, Wilson W L, Sung, Bhooma, Thiruvahindrapuram, Jane, Lougheed, Erwin, Oechslin, Tapas, Mondal, Lynn, Bergin, John, Smythe, Shashank, Jayappa, Vinay J, Rao, Jayaprakash, Shenthar, Perundurai S, Dhandapany, Christopher, Semsarian, Robert G, Weintraub, Richard D, Bagnall, Jodie, Ingles, Marta, Melé, Philipp G, Maass, James, Ellis, Stephen W, Scherer, M, Zarowiecki, and Barcelona Supercomputing Center
Subjects: Genetics & Heredity, RISK, Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Science & Technology, Genetic testing, Cardiomyopathy, FUKUTIN GENE, MEDICAL GENETICS, ASSOCIATION, AMERICAN-COLLEGE, DILATED CARDIOMYOPATHY, Paediatric research, CLASSIFICATION, Gene regulation, carbohydrates (lipids), JOINT CONSENSUS RECOMMENDATION, Genòmica, RESOURCE, Genetics, TRANSCRIPTION FACTOR, Gene expression, Life Sciences & Biomedicine, Molecular Biology, Genetics (clinical), Genetic diseases
Abstract: Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution of variants in non-coding DNA elements that result in cryptic splicing and regulate gene expression has not been explored. We analyzed whole-genome sequencing (WGS) data in a discovery cohort of 209 pediatric CMP patients and 1953 independent replication genomes and exomes. We searched for protein-coding variants, and non-coding variants predicted to affect the function or expression of genes. Thirty-nine percent of cases harbored pathogenic coding variants in known CMP genes, and 5% harbored high-risk loss-of-function (LoF) variants in additional candidate CMP genes. Fifteen percent harbored high-risk regulatory variants in promoters and enhancers of CMP genes (odds ratio 2.25, p = 6.70 × 10−7 versus controls). Genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) were most highly enriched for regulatory variants (odds ratio 6.7–58.1). Functional effects were confirmed in patient myocardium and reporter assays in human cardiomyocytes, and in zebrafish CRISPR knockouts. We provide strong evidence for the genomic contribution of functionally active variants in new genes and in regulatory elements of known CMP genes to early onset CMP. This project was supported by the Ted Rogers Centre for Heart Research (SM, JE), the Canadian Institutes of Health Research (PJT 175034) (SM, JE) and by the Canadian Institutes of Health Research (ENP 161429), under the frame of ERA PerMed (SM). SM holds the Heart and Stroke Foundation of Canada & Robert M Freedom Chair in Cardiovascular Science. SWS holds the GlaxoSmithKline Endowed Chair in Genome Sciences at the Hospital for Sick Children and the University of Toronto. PGM holds a Canada Research Chair Tier 2 in Non-coding Disease Mechanisms. PGM acknowledges the support of the Government of Canada’s New Frontiers in Research Fund (NFRF), [NFRFE-2018-01305]. EO holds the Bitove Family Professorship of Adult Congenital Heart Disease. MM holds a Ramon y Cajal grant from the Spanish Ministry of Science and Innovation (RYC-2017-22249). WO is supported by funding from Fundació La Marató (321/C/2019). JB is funded by a Frans Van de Werf fellowship for clinical cardiovascular research, and by a senior clinical investigator fellowship of the FWO Flanders. KM was a National Science Foundation Graduate Research Fellow under grant no. DGE1144152 during the majority of the project. CS is the recipient of a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (1154992). JI is the recipient of an NHMRC Career Development Fellowship (1162929). RDB is the recipient of a New South Wales Health Cardiovascular Disease Senior Scientist Grant. PSD is supported by the DBT/Wellcome Trust- Indian Alliance. We acknowledge the Labatt Family Heart Centre Biobank at the Hospital for Sick Children for access to DNA samples, and The Centre for Applied Genomics at the Hospital for Sick Children for performing WGS. We thank Xiucheng Cui and Emanuela Pannia for performing the zebrafish experiments at the SickKids Zebrafish Genetics and Disease Models Core (CRISPR-Cas9 and gRNA syntheses, zebrafish embryo microinjections, gRNA PCR validation, qRT-PCR, cardiac imaging). This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. We thank members of the ICGC/PCAWG working groups for generating the variant calls used in our case-control burden analyses. Peer Reviewed "Article signat per 38 autors/es: Robert Lesurf, Abdelrahman Said, Oyediran Akinrinade, Jeroen Breckpot, Kathleen Delfosse, Ting Liu, Roderick Yao, Gabrielle Persad, Fintan McKenna, Ramil R. Noche, Winona Oliveros, Kaia Mattioli, Shreya Shah, Anastasia Miron, Qian Yang, Guoliang Meng, Michelle Chan Seng Yue, Wilson W. L. Sung, Bhooma Thiruvahindrapuram, Jane Lougheed, Erwin Oechslin, Tapas Mondal, Lynn Bergin, John Smythe, Shashank Jayappa, Vinay J. Rao, Jayaprakash Shenthar, Perundurai S. Dhandapany, Christopher Semsarian, Robert G. Weintraub, Richard D. Bagnall, Jodie Ingles, Genomics England Research Consortium, Marta Melé, Philipp G. Maass, James Ellis, Stephen W. Scherer & Seema Mital"
Published: 2022

14. Pharmacological Treatment of Pulmonary Arterial Hypertension in Australia: Current Trends and Challenges

Author: Dominic Keating, P. Steele, Nathan Dwyer, Trevor Williams, Melanie Lavender, David S. Celermajer, John Feenstra, Susanna Proudman, Benjamin Ng, Mark Horrigan, Robert G. Weintraub, Vivek Thakkar, Eugene Kotlyar, Geoff Strange, James Anderson, Nicholas Collins, Jeremy P. Wrobel, Helen Whitford, Anne Keogh, and Edmund M.T. Lau
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Combination therapy, 030204 cardiovascular system & hematology, Pharmacological treatment, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Registries, 030212 general & internal medicine, Disease management (health), Antihypertensive Agents, Aged, Pulmonary Arterial Hypertension, Dose-Response Relationship, Drug, Link function, business.industry, Australia, Middle Aged, medicine.disease, Pulmonary hypertension, Confidence interval, Drug access, Cross-Sectional Studies, Relative risk, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business
Abstract: Combination drug therapy for pulmonary arterial hypertension (PAH) is the international standard of care for most patients, however in Australia there are barriers to drug access. This study evaluates current treatment of PAH patients in Australia and the consistency of therapy with international guidelines.Cross-sectional analysis of patients with Group 1 PAH enrolled in the Pulmonary Hypertension Society of Australia and New Zealand Registry (PHSANZ) at 31 December 2017. Drug treatment was classified as monotherapy or combination therapy and adequacy of treatment was determined by risk status assessment using the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk calculator. Predictors of monotherapy were assessed using a generalised linear model with Poisson distribution and logarithmic link function.1,046 patients met the criteria for analysis. Treatment was classified as monotherapy in 536 (51%) and combination therapy in 510 (49%) cases. Based on REVEAL 2.0, 184 (34%) patients on monotherapy failed to meet low-risk criteria and should be considered inadequately treated. Independent predictors of monotherapy included age greater than 60 years (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.09-1.38; p=0.001), prevalent enrolment in the registry (RR 1.21 [95%CI 1.08-1.36]; p=0.001) and comorbid systemic hypertension (RR 1.17 [95%CI 1.03-1.32]; p=0.014), while idiopathic/heritable/drug-induced PAH subtype (RR 0.85 [95%CI 0.76-0.96]; p=0.006), functional class IV (RR 0.50 [95%CI 0.29-0.86]; p=0.012), increased right ventricular systolic pressure (RR 0.99 [95%CI 0.99-1.00]; p0.001) and increased pulmonary vascular resistance (RR 0.96 [95%CI 0.95-0.98]; p0.001) were less likely to be associated with monotherapy.Most Australian PAH patients are treated with monotherapy and a significant proportion remain at risk of poor outcomes. This is below the standard of care recommended by international guidelines and at risk patients should be escalated to combination therapy.
Published: 2020

15. ISHLT consensus statement on donor organ acceptability and management in pediatric heart transplantation

Author: Renata Shih, Karen Lord, Manuela Camino, Jonathan Smith, Angie Scales, Josef Thul, Dimpna C. Albert, Sanjeev Kumar Khulbey, László Ablonczy, Anna Joong, Sharon Chen, Jacqueline M. Smits, Steven J. Kindel, Oliver Miera, Zdenka Reinhardt, Jens Böhmer, Robert G. Weintraub, Matthew Fenton, Jennifer Conway, Anne I. Dipchand, Michael A. McCulloch, Mariska Kemna, Kenneth R. Knecht, Ryan R. Davies, Javier Castro, Richard Kirk, Melanie D. Everitt, Claire Irving, Jonathan N. Johnson, Deipanjan Nandi, Lara Danziger-Isakov, Peta M. A. Alexander, Maryanne R.K. Chrisant, Dipankar Gupta, Luis Garcia-Guereta, Ashwin K. Lal, Gary Beasley, Gretchen B. Chapman, Janet Scheel, Justin Godown, Steve Zangwill, Susan W. Denfield, Antonio Amodeo, Warren A. Zuckerman, Shahnawaz Amdani, Jeffrey G. Gossett, Estela Azeka, Brian Feingold, David N. Rosenthal, Urs Christen, Iki Adachi, Oliver Niesse, Thomas Möller, Jean A Ballweg, Alicia Pérez-Blanco, Martin Schweiger, Ann Punnoose, Bibhuti B. Das, David M. Peng, Daniel Zimpfer, Alison Butler, and Kimberly Y. Lin
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Consensus, Tissue and Organ Procurement, Scoring system, Waiting Lists, Statement (logic), medicine.medical_treatment, 030204 cardiovascular system & hematology, 030230 surgery, Risk Assessment, Donor Selection, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cardiopulmonary resuscitation, Primary graft failure, Child, Intensive care medicine, Transplantation, business.industry, Graft Survival, Tissue Donors, Donor heart, Heart Transplantation, Surgery, Pediatric heart transplantation, Waitlist mortality, Cardiology and Cardiovascular Medicine, business
Abstract: The number of potential pediatric heart transplant recipients continues to exceed the number of donors, and consequently the waitlist mortality remains significant. Despite this, around 40% of all donated organs are not used and are discarded. This document (62 authors from 53 institutions in 17 countries) evaluates factors responsible for discarding donor hearts and makes recommendations regarding donor heart acceptance. The aim of this statement is to ensure that no usable donor heart is discarded, waitlist mortality is reduced, and post-transplant survival is not adversely impacted.
Published: 2020

16. Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry

Author: Anne Keogh, Carolyn Corrigan, Eugene Kotlyar, James Anderson, Jeremy P. Wrobel, Trevor Williams, Nicholas Collins, Nathan Dwyer, Dominic Keating, Robert G. Weintraub, Helen Whitford, David S. Celermajer, P. Steele, Victor Khou, John Feenstra, Ken Whyte, Melanie Lavender, Tanya McWilliams, Mark Horrigan, Edmund M.T. Lau, and Geoff Strange
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Delayed Diagnosis, Kaplan-Meier Estimate, Disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Epidemiology, Humans, Medicine, Registries, 030212 general & internal medicine, Survival analysis, Pulmonary Arterial Hypertension, business.industry, Vascular disease, Proportional hazards model, Mortality rate, Australia, Hemodynamics, Middle Aged, medicine.disease, Pulmonary hypertension, Logistic Models, 030228 respiratory system, Female, business, New Zealand, Cohort study
Abstract: Background and objective Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. Methods A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. Results A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. Conclusion PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.
Published: 2020

17. A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy

Author: Andreea Dragulescu, Cedric Manlhiot, Chet R. Villa, Tanya Papaz, Carolyn Y. Ho, Iacopo Olivotto, John J. Parent, Robert G. Weintraub, Alexandre C. Pereira, Seema Mital, Lee N. Benson, Pete F. Aziz, John L. Jefferies, Michelle Michels, Taylor S. Howard, Stephanie J. Nakano, Virginie Beauséjour Ladouceur, Samuel G. Wittekind, Joseph W. Rossano, Letizia Gardin, Elizabeth A. Stephenson, Katey R. Armstrong, Myriam Lafreniere-Roula, Steven D. Colan, Chun-Po Steve Fan, Paul F. Kantor, Seshadri Balaji, Mark W. Russell, Jacob Mathew, Marc E. Richmond, Robert Whitehill, Emilie Jean-St-Michel, Ashwin K. Lal, Beth D. Kaufman, Christopher Semsarian, Jodie Ingles, Jennifer Conway, Heather T. Henderson, Justin Godown, Aamir Jeewa, Anastasia Miron, Ryan J. Butts, and Cardiology
Subjects: cardiomyopathies, Male, medicine.medical_specialty, pediatrics, Adolescent, Cardiomyopathy, Risk Assessment, Sudden cardiac death, Risk Factors, Original Research Articles, Physiology (medical), Primary prevention, Internal medicine, medicine, Humans, Public Health Surveillance, Young adult, Child, Retrospective Studies, hypertrophic cardiomyopathy, Models, Statistical, business.industry, Age Factors, Hypertrophic cardiomyopathy, Reproducibility of Results, Cardiomyopathy, Hypertrophic, medicine.disease, death, sudden, heart, defibrillators, implantable, Death, Sudden, Cardiac, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, Female, hypertrophy, Cardiology and Cardiovascular Medicine, business, Algorithms
Abstract: Supplemental Digital Content is available in the text., Background: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. Methods: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy 70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.
Published: 2020

18. Long-term outcomes of staged repair of tetralogy of Fallot

Author: Xin Tao Ye, Edward Buratto, Antonia Schulz, Samuel J. Macalister, Robert G. Weintraub, Christian P. Brizard, and Igor E. Konstantinov
Subjects: Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract: The optimal management strategy for symptomatic young infants with tetralogy of Fallot (TOF) is yet to be determined. We aimed to evaluate the long-term outcomes of a staged approach with initial shunt palliation followed by complete repair.Between January 1993 and July 2021, 160 children with TOF underwent a systemic-to-pulmonary shunt at our institution, including 65 neonates (41%). The mean duration of follow-up was 12.3 ± 8.1 years.Hospital mortality was 3% (4 of 160), all occurring in patients with a shunt size-to-weight ratio ≥1.2 mm/kg. Composite morbidity-defined as cardiac arrest, postoperative mechanical circulatory support, or unplanned reoperation-occurred in 21% (33 of 160). On multivariable analysis, a shunt size-to-weight ratio ≥1.2 mm/kg and prematurity were independent predictors of composite morbidity. Interstage mortality was 3% (4 of 156). A limited transannular patch was used in 75% (113 of 150) of TOF repairs. Actuarial survival at 20 years after shunt was 90% (95% confidence interval [CI], 79%-95%). Actuarial freedom from reinterventions at 20 years after TOF repair was 40% (95% CI, 28%-52%). Neonates had comparable composite morbidity, mortality, and late risk of reinterventions to older children.Staged repair of TOF in symptomatic young infants results in low mortality but high rates of reinterventions at long-term follow-up. A shunt size-to-weight ratio ≥1.2 mm/kg is a significant risk factor for mortality and morbidity prior to complete repair. Neonates undergoing shunt insertion have comparable outcomes to older children.
Published: 2021

19. PPA2-associated sudden cardiac death

Author: Charlotte V. Y. Knowles, Anil Kanthi, Carolyn Tysoe, Georgia Spentzou, Claire L. S. Turner, Jan A Till, Liza K. Phillips, Anne Moreau de Bellaing, Diptendu Chatterjee, Alexandre Janin, Paul French, Tamara T. Koopmann, Anju Shukla, Melanie T. Achleitner, Loïc de Pontual, Matthew S. Edwards, Deborah J. Morris-Rosendahl, Noha Elserafy, Kirti Mittal, Jessie Cameron, Wendy K. Chung, Saskia B. Wortmann, Sajel L Kana, Kit Doudney, Robert G. Weintraub, Peter M George, Priyanka Ahimaz, Kyla Dunn, Ona Faye-Petersen, Katta M. Girisha, Hannah L. Kennedy, Kate S Lichkus, Alexa Kidd, Sumith Parikh, Jason D. Merker, Megan E. Grove, Ruth McGowan, Laura Brett, Anna C.E. Hurst, Jeanne Amiel, Bindu Parayil Sankaran, Dianna G. Fisk, Clémantine Dimartino, Charlotte L. Alston, Michelle L. Thompson, Johannes A. Mayr, Tessa Homfray, Alan Ma, Robert McFarland, Muhammad A Rafiq, Anne Guimier, Robert M Hamilton, Christian Turner, Karen McLeod, Christopher T. Gordon, Robert W. Taylor, David R. Thorburn, Florence van den Broek, Carolyn Ellaway, and Fanny Bajolle
Subjects: Neurological signs, medicine.medical_specialty, Adolescent, Cardiomyopathy, Disease, Article, Sudden cardiac death, Mitochondrial Proteins, Internal medicine, Humans, Medicine, Allele, Alleles, Genetics (clinical), Genetics & Heredity, 0604 Genetics, Science & Technology, business.industry, Sudden cardiac arrest, 1103 Clinical Sciences, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], medicine.disease, DEFICIENCY, Inorganic Pyrophosphatase, Death, Sudden, Cardiac, Child, Preschool, Heart failure, Mutation, Alcohol intake, medicine.symptom, Cardiomyopathies, business, Life Sciences & Biomedicine
Abstract: Purpose Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. Methods Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. Results Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. Conclusion We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.
Published: 2021

20. 1 The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy

Author: Satish Adwani, Ana Usano, Orhan Uzun, Elena Cervi, Toru Kubo, Sergi Cesar, Juan R. Gimeno, Ferran Gran Ipina, Robert G. Weintraub, Jens Mogensen, Anwar Baban, Lidia Ziółkowska, Lucaa Ragni, Sophie Duignan, Adrián Fernández, Ella Fiend, Zdenka Reinhardt, H Walsh, Torsten Bloch Rasmussen, Sian Chivers, Perry M. Elliott, Ingrid King, G Norrish, Georgia Sarquella-Brugada, Caroline Jones, Chiara Marrone, Ana Siles, Tara Bharucha, Terence Prendiville, Piers E.F. Daubeney, Fernando Rueda, Elena Biagini, Vasiliki Vlagkouli, Juan Pablo Kaski, Aris Anastasakis, Silvia Favilli, Constancio Medrano, Chen Qu, Alvarez Garcia-Roves Reyes, Maria Ilina, Peter Kubuš, Rumana Z Omar, Constantin-Cristian Topriceanu, Karen McLeod, FJ Castro Garcia, Drago Drago, Iacopo Olivotto, Jonathan Searle, Regina Bökenkamp, Roberto Barriales-Villa, and Silvia Passantino
Subjects: medicine.medical_specialty, Framingham Risk Score, business.industry, medicine.medical_treatment, Hypertrophic cardiomyopathy, Retrospective cohort study, Implantable cardioverter-defibrillator, medicine.disease, Left ventricular hypertrophy, QT interval, Sudden cardiac death, Internal medicine, medicine, Cardiology, cardiovascular diseases, business, Mace
Abstract: Introduction Sudden cardiac death is the most common cause of mortality in childhood onset hypertrophic cardiomyopathy. Identifying individuals at highest risk is therefore an essential part of clinical care but remains challenging. The 12 lead electrocardiogram (ECG) has been proposed as a useful tool for risk stratification and an ECG risk score has been proposed. However, this has not been independently validated and the ECG phenotype of childhood HCM has not been previously described. The aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods Participants with an available baseline resting 12-lead ECG were identified from a large, international, multi-centre, retrospective cohort of patients aged less than 16 years fulfilling the diagnostic criteria for HCM (n=1029). Resting baseline ECG was evaluated and ECG variables were extracted. In addition, the ECG risk score based on 8 parameters (deviation in QRS axis, pathological T-wave inversion in limb or precordial leads, ST-segment depression, dominant S-wave in V4, limb-lead amplitude sum, 12-lead amplitude duration product and QTc) was calculated as previously described. The primary study endpoint was a composite outcome of major cardiac events (MACE) defined as SCD, resuscitated cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia (VT) with haemodynamic compromise. The discriminatory performance of using an ECG risk score >5 to identify patients at increased risk of MACE at 5 years was determined using Harrell’s C-index. Results Of 356 patients with childhood HCM (68.9% male, mean age at presentation 10.1 ± 4.5 years), 347 (97.5%) had baseline ECG abnormalities such as: repolarization abnormalities (n=277, 77.8%), left ventricular hypertrophy (n=240. 67.6%), abnormal QRS axis (n=126, 35.4%) or QT prolongation (n=131, 36.8%). Over a median follow up of 3.9 years (IQR 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year MACE on univariable or multivariable Cox regression analysis. Of the 164 participants with an ECG score >5, 153 (93.3%) did not have a MACE within 5 years. Harrell’s C-index (the probability of correctly distinguishing between high and low risk patients using an ECG risk score threshold of >5) was 0.60 (95% CI 0.484-0.715) at 5 years. The corresponding positive and negative predictive values were 6.7% (95% CI 4.7 – 9.4%) and 96.9% (95% CI 94.2 – 98.4%). Conclusions In a large, international, multi-centre cohort of children with HCM, ECG abnormalities are common. No ECG characteristic, either in isolation or combined in the ECG risk score, was associated with 5-year MACE risk. This suggests that the role of the baseline ECG phenotype in improving risk stratification in childhood HCM is limited. Conflict of Interest None
Published: 2021

21. Creatinine‐based estimation of glomerular filtration rate in patients with a Fontan circulation

Author: David S. Winlaw, Kathryn Rice, Leeanne Grigg, Thomas G. Wilson, Ajay J. Iyengar, Robert G. Weintraub, Julian Ayer, Michael Cheung, Charlotte E Verrall, Timothy M. Cain, Yves d'Udekem, Karin du Plessis, Rachael Cordina, Thomas L. Gentles, and Padma Rao
Subjects: Male, Cross-sectional study, medicine.medical_treatment, 030204 cardiovascular system & hematology, Fontan Procedure, Kidney, urologic and male genital diseases, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Registries, Child, education.field_of_study, biology, Age Factors, General Medicine, female genital diseases and pregnancy complications, Treatment Outcome, Creatinine, Predictive value of tests, Technetium Tc 99m Pentetate, Female, Kidney Diseases, Cardiology and Cardiovascular Medicine, Glomerular Filtration Rate, Adult, Heart Defects, Congenital, medicine.medical_specialty, Adolescent, Population, Urology, Renal function, Models, Biological, Fontan procedure, Young Adult, 03 medical and health sciences, Predictive Value of Tests, 030225 pediatrics, medicine, Humans, Radiology, Nuclear Medicine and imaging, education, business.industry, Australia, Reproducibility of Results, medicine.disease, Cross-Sectional Studies, chemistry, Cystatin C, Pediatrics, Perinatology and Child Health, biology.protein, Surgery, Radiopharmaceuticals, business, Biomarkers, New Zealand, Kidney disease
Abstract: BACKGROUND: Patients with a Fontan circulation are at risk of renal dysfunction. We analyzed cross-sectional data in pediatric and adult Fontan patients in order to assess the accuracy of commonly used serum creatinine-based methods in estimating glomerular filtration rate (GFR). METHODS: A total of 124 Fontan patients (58 children, 66 adults) were enrolled across three study centers. Measurement of GFR (mGFR) using in vivo 99m Tc-DTPA clearance was performed. Various serum creatinine-based equations were used to calculate estimated GFR (eGFR). RESULTS: Mean mGFR was 108 ± 28 mL/min/1.73 m2 in children and 92 ± 20 mL/min/1.73 m2 in adults. Fourteen children (25%) and 28 adults (45%) had an mGFR
Published: 2019

22. Outcomes of aortic valve repair in children resulting in bicuspid anatomy: Is there a need for tricuspidization?

Author: Antonia Schulz, Edward Buratto, Fraser R.O. Wallace, Nicholas Fulkoski, Robert G. Weintraub, Christian P. Brizard, and Igor E. Konstantinov
Subjects: Reoperation, Pulmonary and Respiratory Medicine, Aortic Valve Insufficiency, Infant, Newborn, Infant, Treatment Outcome, Bicuspid Aortic Valve Disease, Aortic Valve, Humans, Surgery, Cardiac Surgical Procedures, Child, Cardiology and Cardiovascular Medicine, Retrospective Studies
Abstract: We aimed to assess outcomes after aortic valve repair leading to bicuspid valve anatomy in children.This is a retrospective study of patients who underwent aortic valve repair with creation/preservation of bicuspid aortic valve anatomy or tricuspidization of bicuspid valves between 1980 and 2016.Overall, 127 patients underwent bicuspid repair. Median age was 0.73 years (interquartile range, 0.1-8.9), and median weight was 8.15 kg (interquartile range, 3.9-31.7). The cohort included 22.8% neonates (n = 29), 28.3% infants (n = 36), and 48.8% children (n = 62). Repair was performed without a patch in 54.3% (n = 69). Survival at 10 years was 94.8% (95% confidence interval, 87.5-97.85). Freedom from aortic valve reoperation at 5 and 10 years was 79.9% (95% confidence interval, 71.2-86.2) and 65.6% (95% confidence interval, 53.4-75.3), respectively. Re-repair was undertaken in 53.7% (22/41). Freedom from aortic valve replacement at 5 and 10 years was 90.3% (95% confidence interval, 83.1-94.5) and 75.8% (95% confidence interval, 63-84.7), respectively. Risk factors for reoperation were age less than 1 year, unicuspid valve, and the presence of Shone complex and concomitant aortic arch repair. There were 107 patients (107/127, 84.25%) with preoperative bicuspid aortic valve morphology that was preserved. They were compared with a separate cohort of 44 patients who underwent tricuspidization of bicuspid aortic valve during the same period. There was no difference in survival or freedom from aortic valve reoperation. However, freedom from aortic valve replacement was lower after tricuspidization with 49.7% (95% confidence interval, 26.3-69.3) versus 75.8% (95% confidence interval, 62.1-85.1) after 10 years (P = .0118).Aortic valve repair leading to bicuspid valve anatomy in children has satisfactory long-term results. Reoperation remains common, but the need for early valve replacement can be effectively delayed.
Published: 2022

23. Hepatic and renal end-organ damage in the Fontan circulation: A report from the Australian and New Zealand Fontan Registry

Author: Stephen I. Alexander, Winita Hardikar, Robert N. Justo, Julian Ayer, Robert G. Weintraub, Charlotte E Verrall, David S. Celermajer, Michael Cheung, Ajay J. Iyengar, Thomas L. Gentles, Thomas G. Wilson, Gavin R. Wheaton, Padma Rao, Diana Zannino, Andrew Bullock, Dorothy J. Radford, Timothy M. Cain, Judith Barry, Yves d'Udekem, Kathryn Rice, Leeanne Grigg, Rachael Cordina, Karin du Plessis, Janina Chapman, and David S. Winlaw
Subjects: Adult, Male, Research Report, medicine.medical_specialty, Cirrhosis, Adolescent, medicine.medical_treatment, Population, Urology, 030204 cardiovascular system & hematology, Fontan Procedure, Kidney, Inferior vena cava, Fontan procedure, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Registries, education, education.field_of_study, FibroTest, business.industry, Australia, medicine.disease, Cross-Sectional Studies, Liver, medicine.vein, Echocardiography, Female, 030211 gastroenterology & hepatology, Microalbuminuria, Cardiology and Cardiovascular Medicine, Hepatic fibrosis, Transient elastography, business, Glomerular Filtration Rate, New Zealand
Abstract: Background Hepatic and renal dysfunction have been observed in survivors of the Fontan procedure, however their incidence and associated factors remain poorly defined. Methods A total of 152 participants from a Registry of 1528 patients underwent abdominal ultrasound, transient elastography (FibroScan), serum fibrosis score (FibroTest), in vivo Tc-99m DTPA measurement of glomerular filtration rate (mGFR), and urine albumin-creatinine ratio (ACR). Results Mean age and time since Fontan were 19.8 ± 9.3 and 14.1 ± 7.6 years, respectively. Features suggestive of hepatic fibrosis were observed on ultrasound in 87/143 (61%) and no patient was diagnosed with hepatocellular carcinoma. FibroScan median kPa was ≥10 in 117/133 (88%), ≥15 in 75/133 (56%), and ≥20 in 41/133 (31%). Fifty-four patients (54/118, 46%) had a FibroTest score ≥0.49 (equivalent to ≥F2 fibrosis). FibroTest score correlated with FibroScan value (r = 0.24, p = 0.015) and ACR (r = 0.29, p = 0.002), and patients with ultrasound features of hepatic fibrosis had a higher FibroScan median kPa (19.5 vs 15.4, p = 0.002). Renal impairment was mild (mGFR 60–89 ml/min/1.73 m2) in 46/131 (35%) and moderate (mGFR 30–59 ml/min/1.73 m2) in 3/131 (2%). Microalbuminuria was detected in 52/139 participants (37%). By multivariable analysis, time since Fontan was associated with increased FibroScan median kPa (β = 0.89, 95% CI 0.54–1.25, p = 0.002) and decreased mGFR (β = −0.77, 95% CI −1.29–0.24, p = 0.005). Conclusions In the second decade after Fontan hepatic and renal structure and function are abnormal in a significant number of patients: close to 60% have ultrasonographic evidence of structural hepatic abnormalities, 46% have elevated serum hepatic fibrosis scores, and 57% have either reduced glomerular filtration rate or microalbuminuria. Hepatic and renal function should be monitored for potential impacts on outcomes after Fontan completion.
Published: 2018

24. Long-term outcomes of primary aortic valve repair for isolated congenital aortic stenosis in children

Author: Fraser Wallace, Edward Buratto, Antonia Schulz, Yves d’Udekem, Robert G. Weintraub, Christian P. Brizard, and Igor E. Konstantinov
Subjects: Pulmonary and Respiratory Medicine, Heart Defects, Congenital, Reoperation, Aortic Valve Insufficiency, Infant, Newborn, Aortic Valve Stenosis, Treatment Outcome, Aortic Valve, Humans, Surgery, Cardiac Surgical Procedures, Cardiology and Cardiovascular Medicine, Child, Follow-Up Studies, Retrospective Studies
Abstract: We aimed to assess the long-term outcomes of children with isolated congenital aortic stenosis who underwent primary aortic valve repair.Records of all children (n = 111) with isolated congenital aortic stenosis who underwent primary aortic valve repair between 1980 and 2016 were reviewed. An optimal operative outcome consisted of a residual left ventricular outflow tract peak systolic gradient35 mm Hg and trivial or less aortic insufficiency.Median age at surgery was 0.4 years (interquartile range, 1 month-7.9 years) and median weight at surgery was 7.0 kg (interquartile range, 3.7-25.0 kg). Fifty-two patients (46.8%; 52/111) underwent aortic valve repair with the use of patch material. Early mortality was 0.9% (1/111). Late mortality was 0.9% (1/110). Freedom from aortic valve reoperation was 52.1% (95% CI, 38.7-63.8) at 10 years. Freedom from aortic valve replacement was 67.9% (95% CI, 55.4-77.5) at 10 years. An optimal outcome was achieved in 48 patients (43.2%; 48/111). At 10 years, freedom from aortic valve reoperation was 78.2% (95% CI, 63.1-87.8) in patients with an optimal outcome, compared with 39.4% (95% CI, 22.8-55.6) in those with a suboptimal outcome (P = .03). Tricuspid aortic valve was associated with a suboptimal outcome (P = .01).Aortic valve repair achieves relief of congenital aortic stenosis with very low early mortality and excellent long-term survival, even in neonates. Although nearly half of the patients required aortic valve reoperation by 10 years, two-thirds of the patients remain free from aortic valve replacement. An optimal outcome was more commonly achieved with bicuspid aortic valves compared with tricuspid aortic valves.
Published: 2021

25. Response by Mital et al to Letter Regarding Article, 'A Validated Model for Sudden Cardiac Death Risk Prediction in Pediatric Hypertrophic Cardiomyopathy'

Author: Letizia Gardin, Joseph W. Rossano, Jennifer Conway, Anastasia Miron, Steve Fan, Robert G. Weintraub, Myriam Lafreniere-Roula, PRIMaCY Investigators, Ryan J. Butts, Katey R. Armstrong, Seema Mital, Chet R. Villa, Mark W. Russell, Marc E. Richmond, Beth D. Kaufman, and Paul F. Kantor
Subjects: medicine.medical_specialty, business.industry, Physiology (medical), Internal medicine, Cardiology, medicine, MEDLINE, Hypertrophic cardiomyopathy, Cardiology and Cardiovascular Medicine, business, medicine.disease, Sudden cardiac death
Published: 2021

26. The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy

Author: Orhan Uzun, Tara Bharucha, Silvia Passantino, Fernando Rueda, Robert G. Weintraub, Piers E.F. Daubeney, H Walsh, Aris Anastasakis, Terrence Prendiville, Constancio Medrano, Chen Qu, Elena Biagini, Ferran Gran, Toru Kubo, Jonathan Searle, Reyes Alvarez Garcia-Roves, Jens Mogensen, Maria Ilina, Sian Chivers, Peter Kubuš, Adrián Fernández, Satish Adwani, Zdenka Reinhardt, Perry M. Elliott, Fabrizio Drago, Anwar Baban, Gabrielle Norrish, Luca Ragni, Ingrid King, Vasiliki Vlagkouli, Fernandez J Castro, Cristian C. Topriceanu, Georgia Sarquella-Brugada, Caroline Jones, Karen McLeod, Sergi Cesar, Roberto Barriales-Villa, Sophie Duignan, Rumana Z Omar, Silvia Favilli, Juan R. Gimeno, Juan Pablo Kaski, Chiara Marrone, Ana Usano, Elena Cervi, Iacopo Olivotto, Lidia Ziółkowska, Ana Siles, Torsten Bloch Rasmussen, Ella Field, and Regina Bökenkamp
Subjects: medicine.medical_specialty, Electrocardiography/methods, Epidemiology, Cardiomyopathy, Cardiomyopathy, Hypertrophic/complications, QT interval, Sudden death, Risk Assessment, Sudden cardiac death, Electrocardiography, Interquartile range, Risk Factors, Internal medicine, medicine, Humans, cardiovascular diseases, Children, Death, Sudden, Cardiac/epidemiology, Retrospective Studies, Framingham Risk Score, business.industry, Hypertrophic cardiomyopathy, Cardiomyopathy, Hypertrophic, medicine.disease, Electrocardiogram, Death, Sudden, Cardiac, Phenotype, Hypertrophic, Cohort, Cardiology, Cardiology and Cardiovascular Medicine, business
Abstract: Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.
Published: 2021

27. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study

Author: Gregory A. Roth, George A. Mensah, Catherine O. Johnson, Giovanni Addolorato, Enrico Ammirati, Larry M. Baddour, Noël C. Barengo, Andrea Z. Beaton, Emelia J. Benjamin, Catherine P. Benziger, Aimé Bonny, Michael Brauer, Marianne Brodmann, Thomas J. Cahill, Jonathan Carapetis, Alberico L. Catapano, Sumeet S. Chugh, Leslie T. Cooper, Josef Coresh, Michael Criqui, Nicole DeCleene, Kim A. Eagle, Sophia Emmons-Bell, Valery L. Feigin, Joaquim Fernández-Solà, Gerry Fowkes, Emmanuela Gakidou, Scott M. Grundy, Feng J. He, George Howard, Frank Hu, Lesley Inker, Ganesan Karthikeyan, Nicholas Kassebaum, Walter Koroshetz, Carl Lavie, Donald Lloyd-Jones, Hong S. Lu, Antonio Mirijello, Awoke Misganaw Temesgen, Ali Mokdad, Andrew E. Moran, Paul Muntner, Jagat Narula, Bruce Neal, Mpiko Ntsekhe, Glaucia Moraes de Oliveira, Catherine Otto, Mayowa Owolabi, Michael Pratt, Sanjay Rajagopalan, Marissa Reitsma, Antonio Luiz P. Ribeiro, Nancy Rigotti, Anthony Rodgers, Craig Sable, Saate Shakil, Karen Sliwa-Hahnle, Benjamin Stark, Johan Sundström, Patrick Timpel, Imad M. Tleyjeh, Marco Valgimigli, Theo Vos, Paul K. Whelton, Magdi Yacoub, Liesl Zuhlke, Christopher Murray, Valentin Fuster, Noel C. Barengo, Andrea Beaton, Aime Bonny, Jonathan R. Carapetis, Sumeet Chugh, Michael H. Criqui, Nicole K. DeCleene, Joaquim Fernández-Sola, F. Gerry R. Fowkes, Nicholas J. Kassebaum, Walter J. Koroshetz, Awoke T. Misganaw, Ali H. Mokdad, Gláucia M.M. Oliveira, Catherine M. Otto, Mayowa O. Owolabi, Marissa B. Reitsma, Nancy A. Rigotti, Craig A. Sable, Saate S. Shakil, Karen Sliwa, Benjamin A. Stark, Imad I. Tleyjeh, Liesl J. Zuhlke, Mohsen Abbasi-Kangevari, Alireza Abdi, Aidin Abedi, Victor Aboyans, Woldu A. Abrha, Eman Abu-Gharbieh, Abdelrahman I. Abushouk, Dilaram Acharya, Tim Adair, Oladimeji M. Adebayo, Zanfina Ademi, Shailesh M. Advani, Khashayar Afshari, Ashkan Afshin, Gina Agarwal, Pradyumna Agasthi, Sohail Ahmad, Sepideh Ahmadi, Muktar B. Ahmed, Budi Aji, Yonas Akalu, Wuraola Akande-Sholabi, Addis Aklilu, Chisom J. Akunna, Fares Alahdab, Ayman Al-Eyadhy, Khalid F. Alhabib, Sheikh M. Alif, Vahid Alipour, Syed M. Aljunid, François Alla, Amir Almasi-Hashiani, Sami Almustanyir, Rajaa M. Al-Raddadi, Adeladza K. Amegah, Saeed Amini, Arya Aminorroaya, Hubert Amu, Dickson A. Amugsi, Robert Ancuceanu, Deanna Anderlini, Tudorel Andrei, Catalina Liliana Andrei, Alireza Ansari-Moghaddam, Zelalem A. Anteneh, Ippazio Cosimo Antonazzo, Benny Antony, Razique Anwer, Lambert T. Appiah, Jalal Arabloo, Johan Ärnlöv, Kurnia D. Artanti, Zerihun Ataro, Marcel Ausloos, Leticia Avila-Burgos, Asma T. Awan, Mamaru A. Awoke, Henok T. Ayele, Muluken A. Ayza, Samad Azari, Darshan B. B, Nafiseh Baheiraei, Atif A. Baig, Ahad Bakhtiari, Maciej Banach, Palash C. Banik, Emerson A. Baptista, Miguel A. Barboza, Lingkan Barua, Sanjay Basu, Neeraj Bedi, Yannick Béjot, Derrick A. Bennett, Isabela M. Bensenor, Adam E. Berman, Yihienew M. Bezabih, Akshaya S. Bhagavathula, Sonu Bhaskar, Krittika Bhattacharyya, Ali Bijani, Boris Bikbov, Mulugeta M. Birhanu, Archith Boloor, Luisa C. Brant, Hermann Brenner, Nikolay I. Briko, Zahid A. Butt, Florentino Luciano Caetano dos Santos, Leah E. Cahill, Lucero Cahuana-Hurtado, Luis A. Cámera, Ismael R. Campos-Nonato, Carlos Cantu-Brito, Josip Car, Juan J. Carrero, Felix Carvalho, Carlos A. Castañeda-Orjuela, Ferrán Catalá-López, Ester Cerin, Jaykaran Charan, Vijay Kumar Chattu, Simiao Chen, Ken L. Chin, Jee-Young J. Choi, Dinh-Toi Chu, Sheng-Chia Chung, Massimo Cirillo, Sean Coffey, Sara Conti, Vera M. Costa, David K. Cundiff, Omid Dadras, Baye Dagnew, Xiaochen Dai, Albertino A.M. Damasceno, Lalit Dandona, Rakhi Dandona, Kairat Davletov, Vanessa De la Cruz-Góngora, Fernando P. De la Hoz, Jan-Walter De Neve, Edgar Denova-Gutiérrez, Meseret Derbew Molla, Behailu T. Derseh, Rupak Desai, Günther Deuschl, Samath D. Dharmaratne, Meghnath Dhimal, Raja Ram Dhungana, Mostafa Dianatinasab, Daniel Diaz, Shirin Djalalinia, Klara Dokova, Abdel Douiri, Bruce B. Duncan, Andre R. Duraes, Arielle W. Eagan, Sanam Ebtehaj, Aziz Eftekhari, Sahar Eftekharzadeh, Michael Ekholuenetale, Nevine El Nahas, Islam Y. Elgendy, Muhammed Elhadi, Shaimaa I. El-Jaafary, Sadaf Esteghamati, Atkilt E. Etisso, Oghenowede Eyawo, Ibtihal Fadhil, Emerito Jose A. Faraon, Pawan S. Faris, Medhat Farwati, Farshad Farzadfar, Eduarda Fernandes, Carlota Fernandez Prendes, Pietro Ferrara, Irina Filip, Florian Fischer, David Flood, Takeshi Fukumoto, Mohamed M. Gad, Shilpa Gaidhane, Morsaleh Ganji, Jalaj Garg, Abadi K. Gebre, Birhan G. Gebregiorgis, Kidane Z. Gebregzabiher, Gebreamlak G. Gebremeskel, Lemma Getacher, Abera Getachew Obsa, Alireza Ghajar, Ahmad Ghashghaee, Nermin Ghith, Simona Giampaoli, Syed Amir Gilani, Paramjit S. Gill, Richard F. Gillum, Ekaterina V. Glushkova, Elena V. Gnedovskaya, Mahaveer Golechha, Kebebe B. Gonfa, Amir Hossein Goudarzian, Alessandra C. Goulart, Jenny S. Guadamuz, Avirup Guha, Yuming Guo, Rajeev Gupta, Vladimir Hachinski, Nima Hafezi-Nejad, Teklehaimanot G. Haile, Randah R. Hamadeh, Samer Hamidi, Graeme J. Hankey, Arief Hargono, Risky K. Hartono, Maryam Hashemian, Abdiwahab Hashi, Shoaib Hassan, Hamid Y. Hassen, Rasmus J. Havmoeller, Simon I. Hay, Khezar Hayat, Golnaz Heidari, Claudiu Herteliu, Ramesh Holla, Mostafa Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Mowafa Househ, Junjie Huang, Ayesha Humayun, Ivo Iavicoli, Charles U. Ibeneme, Segun E. Ibitoye, Olayinka S. Ilesanmi, Irena M. Ilic, Milena D. Ilic, Usman Iqbal, Seyed Sina N. Irvani, Sheikh Mohammed Shariful Islam, Rakibul M. Islam, Hiroyasu Iso, Masao Iwagami, Vardhmaan Jain, Tahereh Javaheri, Sathish Kumar Jayapal, Shubha Jayaram, Ranil Jayawardena, Panniyammakal Jeemon, Ravi P. Jha, Jost B. Jonas, Jitendra Jonnagaddala, Farahnaz Joukar, Jacek J. Jozwiak, Mikk Jürisson, Ali Kabir, Tanvir Kahlon, Rizwan Kalani, Rohollah Kalhor, Ashwin Kamath, Ibrahim Kamel, Himal Kandel, Amit Kandel, André Karch, Ayele Semachew Kasa, Patrick D.M.C. Katoto, Gbenga A. Kayode, Yousef S. Khader, Mohammad Khammarnia, Muhammad S. Khan, Md Nuruzzaman Khan, Maseer Khan, Ejaz A. Khan, Khaled Khatab, Gulam M.A. Kibria, Yun Jin Kim, Gyu Ri Kim, Ruth W. Kimokoti, Sezer Kisa, Adnan Kisa, Mika Kivimäki, Dhaval Kolte, Ali Koolivand, Vladimir A. Korshunov, Sindhura Lakshmi Koulmane Laxminarayana, Ai Koyanagi, Kewal Krishan, Vijay Krishnamoorthy, Barthelemy Kuate Defo, Burcu Kucuk Bicer, Vaman Kulkarni, G. Anil Kumar, Nithin Kumar, Om P. Kurmi, Dian Kusuma, Gene F. Kwan, Carlo La Vecchia, Ben Lacey, Tea Lallukka, Qing Lan, Savita Lasrado, Zohra S. Lassi, Paolo Lauriola, Wayne R. Lawrence, Avula Laxmaiah, Kate E. LeGrand, Ming-Chieh Li, Bingyu Li, Shanshan Li, Stephen S. Lim, Lee-Ling Lim, Hualiang Lin, Ziqiang Lin, Ro-Ting Lin, Xuefeng Liu, Alan D. Lopez, Stefan Lorkowski, Paulo A. Lotufo, Alessandra Lugo, Nirmal K. M, Fabiana Madotto, Morteza Mahmoudi, Azeem Majeed, Reza Malekzadeh, Ahmad A. Malik, Abdullah A. Mamun, Navid Manafi, Mohammad Ali Mansournia, Lorenzo G. Mantovani, Santi Martini, Manu R. Mathur, Giampiero Mazzaglia, Suresh Mehata, Man Mohan Mehndiratta, Toni Meier, Ritesh G. Menezes, Atte Meretoja, Tomislav Mestrovic, Bartosz Miazgowski, Tomasz Miazgowski, Irmina Maria Michalek, Ted R. Miller, Erkin M. Mirrakhimov, Hamed Mirzaei, Babak Moazen, Masoud Moghadaszadeh, Yousef Mohammad, Dara K. Mohammad, Shafiu Mohammed, Mohammed A. Mohammed, Yaser Mokhayeri, Mariam Molokhia, Ahmed A. Montasir, Ghobad Moradi, Rahmatollah Moradzadeh, Paula Moraga, Lidia Morawska, Ilais Moreno Velásquez, Jakub Morze, Sumaira Mubarik, Walter Muruet, Kamarul Imran Musa, Ahamarshan J. Nagarajan, Mahdi Nalini, Vinay Nangia, Atta Abbas Naqvi, Sreenivas Narasimha Swamy, Bruno R. Nascimento, Vinod C. Nayak, Javad Nazari, Milad Nazarzadeh, Ruxandra I. Negoi, Sandhya Neupane Kandel, Huong L.T. Nguyen, Molly R. Nixon, Bo Norrving, Jean Jacques Noubiap, Brice E. Nouthe, Christoph Nowak, Oluwakemi O. Odukoya, Felix A. Ogbo, Andrew T. Olagunju, Hans Orru, Alberto Ortiz, Samuel M. Ostroff, Jagadish Rao Padubidri, Raffaele Palladino, Adrian Pana, Songhomitra Panda-Jonas, Utsav Parekh, Eun-Cheol Park, Mojtaba Parvizi, Fatemeh Pashazadeh Kan, Urvish K. Patel, Mona Pathak, Rajan Paudel, Veincent Christian F. Pepito, Arokiasamy Perianayagam, Norberto Perico, Hai Q. Pham, Thomas Pilgrim, Michael A. Piradov, Farhad Pishgar, Vivek Podder, Roman V. Polibin, Akram Pourshams, Dimas R.A. Pribadi, Navid Rabiee, Mohammad Rabiee, Amir Radfar, Alireza Rafiei, Fakher Rahim, Vafa Rahimi-Movaghar, Mohammad Hifz Ur Rahman, Muhammad Aziz Rahman, Amir Masoud Rahmani, Ivo Rakovac, Pradhum Ram, Sudha Ramalingam, Juwel Rana, Priyanga Ranasinghe, Sowmya J. Rao, Priya Rathi, Lal Rawal, Wasiq F. Rawasia, Reza Rawassizadeh, Giuseppe Remuzzi, Andre M.N. Renzaho, Aziz Rezapour, Seyed Mohammad Riahi, Ross L. Roberts-Thomson, Leonardo Roever, Peter Rohloff, Michele Romoli, Gholamreza Roshandel, Godfrey M. Rwegerera, Seyedmohammad Saadatagah, Maha M. Saber-Ayad, Siamak Sabour, Simona Sacco, Masoumeh Sadeghi, Sahar Saeedi Moghaddam, Saeed Safari, Amirhossein Sahebkar, Sana Salehi, Hamideh Salimzadeh, Mehrnoosh Samaei, Abdallah M. Samy, Itamar S. Santos, Milena M. Santric-Milicevic, Nizal Sarrafzadegan, Arash Sarveazad, Thirunavukkarasu Sathish, Monika Sawhney, Mete Saylan, Maria I. Schmidt, Aletta E. Schutte, Subramanian Senthilkumaran, Sadaf G. Sepanlou, Feng Sha, Saeed Shahabi, Izza Shahid, Masood A. Shaikh, Mahdi Shamali, Morteza Shamsizadeh, Md Shajedur Rahman Shawon, Aziz Sheikh, Mika Shigematsu, Min-Jeong Shin, Jae Il Shin, Rahman Shiri, Ivy Shiue, Kerem Shuval, Soraya Siabani, Tariq J. Siddiqi, Diego A.S. Silva, Jasvinder A. Singh, Ambrish Singh Mtech, Valentin Y. Skryabin, Anna A. Skryabina, Amin Soheili, Emma E. Spurlock, Leo Stockfelt, Stefan Stortecky, Saverio Stranges, Rizwan Suliankatchi Abdulkader, Hooman Tadbiri, Eyayou G. Tadesse, Degena B. Tadesse, Masih Tajdini, Md Tariqujjaman, Berhane F. Teklehaimanot, Mohamad-Hani Temsah, Ayenew K. Tesema, Bhaskar Thakur, Kavumpurathu R. Thankappan, Rekha Thapar, Amanda G. Thrift, Binod Timalsina, Marcello Tonelli, Mathilde Touvier, Marcos R. Tovani-Palone, Avnish Tripathi, Jaya P. Tripathy, Thomas C. Truelsen, Guesh M. Tsegay, Gebiyaw W. Tsegaye, Nikolaos Tsilimparis, Biruk S. Tusa, Stefanos Tyrovolas, Krishna Kishore Umapathi, Brigid Unim, Bhaskaran Unnikrishnan, Muhammad S. Usman, Muthiah Vaduganathan, Pascual R. Valdez, Tommi J. Vasankari, Diana Z. Velazquez, Narayanaswamy Venketasubramanian, Giang T. Vu, Isidora S. Vujcic, Yasir Waheed, Yanzhong Wang, Fang Wang, Jingkai Wei, Robert G. Weintraub, Abrha H. Weldemariam, Ronny Westerman, Andrea S. Winkler, Charles S. Wiysonge, Charles D.A. Wolfe, Befikadu Legesse Wubishet, Gelin Xu, Ali Yadollahpour, Kazumasa Yamagishi, Lijing L. Yan, Srikanth Yandrapalli, Yuichiro Yano, Hiroshi Yatsuya, Tomas Y. Yeheyis, Yigizie Yeshaw, Christopher S. Yilgwan, Naohiro Yonemoto, Chuanhua Yu, Hasan Yusefzadeh, Geevar Zachariah, Sojib Bin Zaman, Muhammed S. Zaman, Maryam Zamanian, Ramin Zand, Alireza Zandifar, Afshin Zarghi, Mikhail S. Zastrozhin, Anasthasia Zastrozhina, Zhi-Jiang Zhang, Yunquan Zhang, Wangjian Zhang, Chenwen Zhong, Zhiyong Zou, Yves Miel H. Zuniga, and Christopher J.L. Murray
Subjects: BMI, body mass index, GBD, Global Burden of Diseases, Injuries, and Risk Factors Study, IS, ischemic stroke, 030204 cardiovascular system & hematology, MV, mitral valve, SDI, sociodemographic index, Global Health, UI, uncertainty interval, Global Burden of Disease, GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group, 0302 clinical medicine, Cost of Illness, LDL, low-density lipoprotein, Case fatality rate, Global health, 030212 general & internal medicine, IKF, impaired kidney function, 1102 Cardiorespiratory Medicine and Haematology, Incidence (epidemiology), Health Policy, IHD, ischemic heart disease, 1. No poverty, AC, alcoholic cardiomyopathy, 3. Good health, HICs, high-income countries, Cardiovascular Diseases, DALYs, disability-adjusted life years, TMREL, theoretical minimum risk exposure level, Public Health, HHD, hypertensive heart disease, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, AF, atrial fibrillation, Population health, CVD, cardiovascular disease, LMICs, low- and middle-income countries, PM, particulate matter, 1117 Public Health and Health Services, 03 medical and health sciences, JACC State-of-the-Art Review, RHD, rheumatic heart disease, Environmental health, medicine, Humans, LPA, low physical activity, YLLs, years of life lost, Health policy, Disease burden, PAD, peripheral artery disease, business.industry, SBP, systolic blood pressure, Public health, CKD, chronic kidney disease, The Present and Future, AFL, atrial flutter, Correction, HAP, household air pollution, ICD, International Classification of Diseases, CAVD, calcific aortic valve disease, YLDs, years lived with disability, Years of potential life lost, CHA, congenital heart anomalies, Cardiovascular System & Hematology, Heart Disease Risk Factors, business, population health
Abstract: Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases., Central Illustration, Highlights • The burden of CVD, in number of DALYs and deaths, continues to increase globally. • CVD burden attributable to modifiable risk factors continues to increase globally. • Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.
Published: 2020

28. Global burden of 87 risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Soufiane Boufous, Yousef Veisani, Mehran Asadi-Aliabadi, Sharath Burugina Nagaraja, Maziar Moradi-Lakeh, Getachew Mullu Kassa, Edward J Mills, Dimas Ria Angga Pribadi, William James Dangel, Mohamad-Hani Temsah, Catherine O. Johnson, Gregory A. Roth, Giuseppe Gorini, Fariborz Mansour-Ghanaei, Alberto Ortiz, Samad Azari, Assefa Ayalew Ayalew Ayalew Gebreslassie, Salime Goharinezhad, Stephanie R. M. Zimsen, Peng Zheng, Michael Assmus, Elisabetta Pupillo, Bach Xuan Tran, Lal B. Rawal, Narayanaswamy Venketasubramanian, Noushin Mohammadifard, Stephen S Lim, Ata Rafiee, Maria Inês Schmidt, Vincent C. Iannucci, Suzanne Lyn Barker-Collo, Leah E. Cahill, Tauseef Ahmad, Platon D. Lopukhov, Kazumasa Yamagishi, Abdullah Al Mamun, Iqbal R. F. Elyazar, Giovanni Damiani, Mohammad Hossein Bakhshaei, Mehdi Fazlzadeh, Virginia Núñez-Samudio, Alyssa Pennini, Dietrich Plass, Atkilt Esaiyas Etisso, Gebre Teklemariam Demoz, Alexandrea Watson, Arvin Haj-Mirzaian, Paul S Briant, Frank B. Osei, Blair R. Bumgarner, Maciej Banach, Ravensara S. Travillian, Kai-Lan Chang, Shirin Djalalinia, Hasan Yusefzadeh, Silvano Gallus, Seyyed Meysam Mousavi, Bernhard T. Baune, Aaron van Donkelaar, Azeem Majeed, Hans Kromhout, Robert Ancuceanu, Blessing J. Akombi, Pushpendra Singh, Nayu Ikeda, William M. Gardner, Zahid A Butt, Mohammad Abdollahi, Temesgen Yihunie Akalu, Rahman Shiri, Benn Sartorius, Ai-Min Wu, Bing Fang Hwang, Flavia M. Cicuttini, Hiroyasu Iso, Luis Camera, Amin Soheili, Félix Carvalho, Yun Jin Kim, Caleb Mackay Salpeter Irvine, Mehdi Mirzaei-Alavijeh, Iman Halvaei, Saqib Ali, Giulio Castelpietra, Catalina Liliana Andrei, Ali Kazemi Karyani, Parkes J Kendrick, Hamidreza Haririan, Lucas Guimarães Abreu, Mukhammad David Naimzada, Jeff T. Zhao, Samiah Alam, Sorin Hostiuc, Shaun Wen Huey Lee, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Cyrus Alinia, Takahiro Tabuchi, Manu Raj Mathur, Søren Thorgaard Skou, Thomas Khaled Dwayne Classen, Reza Heidari-Soureshjani, Massimo Cirillo, Nikita Otstavnov, Mehdi Bohluli, Ruth W. Kimokoti, Animut Tagele Tamiru, Masoumeh Sadeghi, Mohammad Ali Jahani, Itamar S. Santos, Mekdes Tigistu Yilma, Lars Johansson, Arielle Wilder Eagan, Nevine El Nahas, Silvia Schiavolin, Kevin D. Shield, Dinh-Toi Chu, Shiva Borzouei, Paul S. F. Yip, Beatrix Haddock, Gianfranco Alicandro, Vasily Vlassov, Deanna Anderlini, Giuseppe Remuzzi, Khalid A Altirkawi, Farahnaz Joukar, Aso Mohammad Darwesh, Ratilal Lalloo, Panniyammakal Jeemon, Rohollah Kalhor, Daniel Youngwhan Cho, Weijia Fu, João Pedro Silva, Rodrigo Sarmiento-Suarez, Seth Christopher Yaw Appiah, Mehdi Ahmadi, Jacob Olusegun Olusanya, José Neves, Gaorui Guo, Tomas Y. Yeheyis, John S. Ji, Charles D. H. Parry, Maryam Ghadimi, Seyed-Mohammad Fereshtehnejad, Serge Resnikoff, Anna E. Torre, Vinod C Nayak, Jamileh Shadid, Susanne Breitner, Mohammad Khammarnia, Mathilde Touvier, Ensiyeh Jenabi, Hosna Janjani, Floriane Ausloos, Irmina Maria Michalek, Alexandra S. Boon-Dooley, Jessica A. Cruz, Syed Mohamed Aljunid, Abiodun M. Adeoye, André Faro, Bartosz Miazgowski, Jobert Richie Nansseu, Erin C Mullany, Giannina Ferrara, Martin McKee, Emmanuel Peprah, Oommen John, Reza Saeedi, Yasser Vasseghian, Dragos Virgil Davitoiu, Sarah Wulf Hanson, Yingxi Zhao, Omid Shafaat, Ali Rajabpour-Sanati, Farid Najafi, Ana Maria Mantilla Herrera, Fatemeh Rajati, Tarun Gupta, Łukasz Szumowski, Mohammed Ibrahim Mohialdeen Gubari, Peter Njenga Keiyoro, Dharmesh Kumar Lal, Zhi Jiang Zhang, Osayomwanbo Osarenotor, Tanvir M. Huda, Perminder S. Sachdev, Farhad Ghamari, Era Upadhyay, Vivek Kumar, Guoqing Hu, Vinay Nangia, Vladimir Andreevich Korshunov, Saeed Shahabi, Golnaz Heidari, Ashraf Nabhan, Robert C. 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Mini, Christian Razo, Manuela L. Ferreira, Diego De Leo, Francesco Saverio Violante, Aristidis Tsatsakis, Zahra Sadat Dibaji Forooshani, Tea Lallukka, Dickson A. Amugsi, Anna Poznańska, Graeme J. Hankey, Kewal Krishan, Maryam Zamanian, Eirini Skiadaresi, Jai K Das, Felix Greaves, Tessa M. Pilz, Sameer Vali Gopalani, Mansour Ghafourifard, M. DeLang, Morteza Mahmoudi, Alton Lu, Brian J. Hall, Ravi Prakash Jha, David Edvardsson, Xiu Ju George Zhao, Farshad Farzadfar, Hadi Hassankhani, Samuel M. Ostroff, Gerhard Sulo, Keyghobad Ghadiri, Neeraj Bhala, Stefan Lorkowski, Mohammad Rabiee, Sivan Yegnanarayana Iyer Saraswathy, Amirhossein Sahebkar, Rashid Abdi Guled, Abdallah M. Samy, Roman Topor-Madry, Michal Grivna, Afsaneh Arzani, Ayesha Humayun, Simin Liu, Maryam Khayamzadeh, Davoud Adham, Ahad Bakhtiari, Shafiu Mohammed, Paolo Lauriola, Abbas Mosapour, Sophia Emmons-Bell, Khurshid Alam, Rajat Das Gupta, Matilde Leonardi, Muktar Beshir Ahmed, Jeffrey V. Lazarus, Mohamed M. 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Djalalinia, S, Do, H, Dokova, K, Dorostkar, F, Doshmangir, L, Driscoll, T, Duncan, B, Duraes, A, Eagan, A, Edvardsson, D, El Nahas, N, El Sayed, I, El Tantawi, M, Elbarazi, I, Elgendy, I, El-Jaafary, S, Elyazar, I, Emmons-Bell, S, Erskine, H, Eskandarieh, S, Esmaeilnejad, S, Esteghamati, A, Estep, K, Etemadi, A, Etisso, A, Fanzo, J, Farahmand, M, Fareed, M, Faridnia, R, Farioli, A, Faro, A, Faruque, M, Farzadfar, F, Fattahi, N, Fazlzadeh, M, Feigin, V, Feldman, R, Fereshtehnejad, S, Fernandes, E, Ferrara, G, Ferrari, A, Ferreira, M, Filip, I, Fischer, F, Fisher, J, Flor, L, Foigt, N, Folayan, M, Fomenkov, A, Force, L, Foroutan, M, Franklin, R, Freitas, M, Fu, W, Fukumoto, T, Furtado, J, Gad, M, Gakidou, E, Gallus, S, Garcia-Basteiro, A, Gardner, W, Geberemariyam, B, Ayalew Gebreslassie, A, Geremew, A, Gershberg Hayoon, A, Gething, P, Ghadimi, M, Ghadiri, K, Ghaffarifar, F, Ghafourifard, M, Ghamari, F, Ghashghaee, A, Ghiasvand, H, Ghith, N, Gholamian, A, Ghosh, R, Gill, P, Ginindza, T, Giussani, G, Gnedovskaya, E, Goharinezhad, S, Gopalani, S, Gorini, G, Goudarzi, H, Goulart, A, Greaves, F, Grivna, M, Grosso, G, Gubari, M, Gugnani, H, Guimaraes, R, Guled, R, Guo, G, Guo, Y, Gupta, R, Gupta, T, Haddock, B, Hafezi-Nejad, N, Hafiz, A, Haj-Mirzaian, A, Hall, B, Halvaei, I, Hamadeh, R, Hamidi, S, Hammer, M, Hankey, G, Haririan, H, Haro, J, Hasaballah, A, Hasan, M, Hasanpoor, E, Hashi, A, Hassanipour, S, Hassankhani, H, Havmoeller, R, Hay, S, Hayat, K, Heidari, G, Heidari-Soureshjani, R, Henrikson, H, Herbert, M, Herteliu, C, Heydarpour, F, Hird, T, Hoek, H, Holla, R, Hoogar, P, Hosgood, H, Hossain, N, Hosseini, M, Hosseinzadeh, M, Hostiuc, M, Hostiuc, S, Househ, M, Hsairi, M, Hsieh, V, Hu, G, Hu, K, Huda, T, Humayun, A, Huynh, C, Hwang, B, Iannucci, V, Ibitoye, S, Ikeda, N, Ikuta, K, Ilesanmi, O, Ilic, I, Ilic, M, Inbaraj, L, Ippolito, H, Iqbal, U, Irvani, S, Irvine, C, Islam, M, Islam, S, Iso, H, Ivers, R, Iwu, C, Iyamu, I, Jaafari, J, Jacobsen, K, Jafari, H, Jafarinia, M, Jahani, M, Jakovljevic, M, Jalilian, F, James, S, Janjani, H, Javaheri, T, Javidnia, J, Jeemon, P, Jenabi, E, Jha, R, Jha, V, Ji, J, Johansson, L, John, O, John-Akinola, Y, Johnson, C, Jonas, J, Joukar, F, Jozwiak, J, Jurisson, M, Kabir, A, Kabir, Z, Kalani, H, Kalani, R, Kalankesh, L, Kalhor, R, Kanchan, T, Kapoor, N, Matin, B, Karch, A, Karim, M, Kassa, G, Katikireddi, S, Kayode, G, Kazemi Karyani, A, Keiyoro, P, Keller, C, Kemmer, L, Kendrick, P, Khalid, N, Khammarnia, M, Khan, E, Khan, M, Khatab, K, Khater, M, Khatib, M, Khayamzadeh, M, Khazaei, S, Kieling, C, Kim, Y, Kimokoti, R, Kisa, A, Kisa, S, Kivimaki, M, Knibbs, L, Knudsen, A, Kocarnik, J, Kochhar, S, Kopec, J, Korshunov, V, Koul, P, Koyanagi, A, Kraemer, M, Krishan, K, Krohn, K, Kromhout, H, Kuate Defo, B, Kumar, G, Kumar, V, Kurmi, O, Kusuma, D, La Vecchia, C, Lal, D, Lalloo, R, Lallukka, T, Lami, F, Landires, I, Lang, J, Langan, S, Larsson, A, Lasrado, S, Lauriola, P, Lazarus, J, Lee, P, Lee, S, Legrand, K, Leigh, J, Leonardi, M, Lescinsky, H, Leung, J, Levi, M, Li, S, Lim, L, Linn, S, Liu, S, Liu, Y, Lo, J, Lopez, A, Lopez, J, Lopukhov, P, Lorkowski, S, Lotufo, P, Lu, A, Lugo, A, Maddison, E, Mahasha, P, Mahdavi, M, Mahmoudi, M, Majeed, A, Maleki, A, Maleki, S, Malekzadeh, R, Malta, D, Mamun, A, Manda, A, Manguerra, H, Mansour-Ghanaei, F, Mansouri, B, Mansournia, M, Mantilla Herrera, A, Maravilla, J, Marks, A, Martin, R, Martini, S, Martins-Melo, F, Masaka, A, Masoumi, S, Mathur, M, Matsushita, K, Maulik, P, Mcalinden, C, Mcgrath, J, Mckee, M, Mehndiratta, M, Mehri, F, Mehta, K, Memish, Z, Mendoza, W, Menezes, R, Mengesha, E, Mereke, A, Mereta, S, Meretoja, A, Meretoja, T, Mestrovic, T, Miazgowski, B, Miazgowski, T, Michalek, I, Miller, T, Mills, E, Mini, G, Miri, M, Mirica, A, Mirrakhimov, E, Mirzaei, H, Mirzaei, M, Mirzaei, R, Mirzaei-Alavijeh, M, Misganaw, A, Mithra, P, Moazen, B, Mohammad, D, Mohammad, Y, Mohammad Gholi Mezerji, N, Mohammadian-Hafshejani, A, Mohammadifard, N, Mohammadpourhodki, R, Mohammed, A, Mohammed, H, Mohammed, J, Mohammed, S, Mokdad, A, Molokhia, M, Monasta, L, Mooney, M, Moradi, G, Moradi, M, Moradi-Lakeh, M, Moradzadeh, R, Moraga, P, Morawska, L, Morgado-Da-Costa, J, Morrison, S, Mosapour, A, Mosser, J, Mouodi, S, Mousavi, S, Khaneghah, A, Mueller, U, Mukhopadhyay, S, Mullany, E, Musa, K, Muthupandian, S, Nabhan, A, Naderi, M, Nagarajan, A, Nagel, G, Naghavi, M, Naghshtabrizi, B, Naimzada, M, Najafi, F, Nangia, V, Nansseu, J, Naserbakht, M, Nayak, V, Negoi, I, Ngunjiri, J, Nguyen, C, Nguyen, H, Nguyen, M, Nigatu, Y, Nikbakhsh, R, Nixon, M, Nnaji, C, Nomura, S, Norrving, B, Noubiap, J, Nowak, C, Nunez-Samudio, V, Oancea, B, Odell, C, Ogbo, F, Oh, I, Okunga, E, Oladnabi, M, Olagunju, A, Olusanya, B, Olusanya, J, Omer, M, Ong, K, Onwujekwe, O, Orpana, H, Ortiz, A, Osarenotor, O, Osei, F, Ostroff, S, Otoiu, A, Otstavnov, N, Otstavnov, S, Overland, S, Owolabi, M, Mahesh, P, Padubidri, J, Palladino, R, Panda-Jonas, S, Pandey, A, Parry, C, Pasovic, M, Pasupula, D, Patel, S, Pathak, M, Patten, S, Patton, G, Toroudi, H, Peden, A, Pennini, A, Pepito, V, Peprah, E, Pereira, D, Pesudovs, K, Pham, H, Phillips, M, Piccinelli, C, Pilz, T, Piradov, M, Pirsaheb, M, Plass, D, Polinder, S, Polkinghorne, K, Pond, C, Postma, M, Pourjafar, H, Pourmalek, F, Poznanska, A, Prada, S, Prakash, V, Pribadi, D, Pupillo, E, Syed, Z, Rabiee, M, Rabiee, N, Radfar, A, Rafiee, A, Raggi, A, Rahman, M, Rajabpour-Sanati, A, Rajati, F, Rakovac, I, Ram, P, Ramezanzadeh, K, Ranabhat, C, Rao, P, Rao, S, Rashedi, V, Rathi, P, Rawaf, D, Rawaf, S, Rawal, L, Rawassizadeh, R, Rawat, R, Razo, C, Redford, S, Reiner, R, Reitsma, M, Remuzzi, G, Renjith, V, Renzaho, A, Resnikoff, S, Rezaei, N, Rezapour, A, Rhinehart, P, Riahi, S, Ribeiro, D, Rickard, J, Rivera, J, Roberts, N, Rodriguez-Ramirez, S, Roever, L, Ronfani, L, Room, R, Roshandel, G, Roth, G, Rothenbacher, D, Rubagotti, E, Rwegerera, G, Sabour, S, Sachdev, P, Saddik, B, Sadeghi, E, Sadeghi, M, Saeedi, R, Saeedi Moghaddam, S, Safari, Y, Safi, S, Safiri, S, Sagar, R, Sahebkar, A, Sajadi, S, Salam, N, Salamati, P, Salem, H, Salem, M, Salimzadeh, H, Salman, O, Salomon, J, Samad, Z, Samadi Kafil, H, Sambala, E, Samy, A, Sanabria, J, Sanchez-Pimienta, T, Santomauro, D, Santos, I, Santos, J, Santric-Milicevic, M, Saraswathy, S, Sarmiento-Suarez, R, Sarrafzadegan, N, Sarveazad, A, Sathian, B, Sathish, T, Sattin, D, Saxena, S, Schaeffer, L, Schiavolin, S, Schlaich, M, Schmidt, M, Schutte, A, Schwebel, D, Schwendicke, F, Senbeta, A, Senthilkumaran, S, Sepanlou, S, Serdar, B, Serre, M, Shadid, J, Shafaat, O, Shahabi, S, Shaheen, A, Shaikh, M, Shalash, A, Shams-Beyranvand, M, Shamsizadeh, M, Sharafi, K, Sheikh, A, Sheikhtaheri, A, Shibuya, K, Shield, K, Shigematsu, M, Shin, J, Shin, M, Shiri, R, Shirkoohi, R, Shuval, K, Siabani, S, Sierpinski, R, Sigfusdottir, I, Sigurvinsdottir, R, Silva, J, Simpson, K, Singh, J, Singh, P, Skiadaresi, E, Skou, S, Skryabin, V, Smith, E, Soheili, A, Soltani, S, Soofi, M, Sorensen, R, Soriano, J, Sorrie, M, Soshnikov, S, Soyiri, I, Spencer, C, Spotin, A, Sreeramareddy, C, Srinivasan, V, Stanaway, J, Stein, C, Stein, D, Steiner, C, Stockfelt, L, Stokes, M, Straif, K, Stubbs, J, Sufiyan, M, Suleria, H, Suliankatchi Abdulkader, R, Sulo, G, Sultan, I, Tabares-Seisdedos, R, Tabb, K, Tabuchi, T, Taherkhani, A, Tajdini, M, Takahashi, K, Takala, J, Tamiru, A, Taveira, N, Tehrani-Banihashemi, A, Temsah, M, Tesema, G, Tessema, Z, Thurston, G, Titova, M, Tohidinik, H, Tonelli, M, Topor-Madry, R, Topouzis, F, Torre, A, Touvier, M, Tovani-Palone, M, Tran, B, Travillian, R, Tsatsakis, A, Tudor Car, L, Tyrovolas, S, Uddin, R, Umeokonkwo, C, Unnikrishnan, B, Upadhyay, E, Vacante, M, Valdez, P, van Donkelaar, A, Vasankari, T, Vasseghian, Y, Veisani, Y, Venketasubramanian, N, Violante, F, Vlassov, V, Vollset, S, Vos, T, Vukovic, R, Waheed, Y, Wallin, M, Wang, Y, Watson, A, Wei, J, Wei, M, Weintraub, R, Weiss, J, Werdecker, A, West, J, Westerman, R, Whisnant, J, Whiteford, H, Wiens, K, Wolfe, C, Wozniak, S, Wu, A, Wu, J, Wulf Hanson, S, Xu, G, Xu, R, Yadgir, S, Yahyazadeh Jabbari, S, Yamagishi, K, Yaminfirooz, M, Yano, Y, Yaya, S, Yazdi-Feyzabadi, V, Yeheyis, T, Yilgwan, C, Yilma, M, Yip, P, Yonemoto, N, Younis, M, Younker, T, Yousefi, B, Yousefi, Z, Yousefinezhadi, T, Yousuf, A, Yu, C, Yusefzadeh, H, Moghadam, T, Zamani, M, Zamanian, M, Zandian, H, Zastrozhin, M, Zhang, Y, Zhang, Z, Zhao, J, Zhao, X, Zhao, Y, Zheng, P, Zhou, M, Ziapour, A, Zimsen, S, Lim, S, Murray, C, GBD 2019 Risk Factors Collaborator, Violante FS, Biosciences, Department of Public Health, Clinicum, Department of Neurosciences, HUS Comprehensive Cancer Center, Environmental Sciences, Sub Foundations&PhilosophyofNaturSc begr, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Public Health, Bin Sayeed, M. S. B., Caetano Dos Santos, F. L., Camera, L. A., Elyazar, I. R. F., Ayalew Gebreslassie, A. A. A., Ginindza, T. G., Matin, B. K., Morgado-Da-Costa, J., Khaneghah, A. M., Mahesh, P. A., Toroudi, H. P., Syed, Z. Q., Salem, M. R., Skou, S. T., Tovani-Palone, M. R., Tudor Car, L. T., and Moghadam, T. Z.
Subjects: Male, Nutritional Sciences, Specific risk, Contaminación del Aire Interior, 030204 cardiovascular system & hematology, Socioeconomic Factor, systematic analysis, Global Health, Body Mass Index, Global Burden of Disease, Health Risk Behavior, Health Risk Behaviors, Disease studies, 0302 clinical medicine, Risk Factors, METABOLIC RISKS, 030212 general & internal medicine, 11 Medical and Health Sciences, Factores de Riesgo, 2. Zero hunger, education.field_of_study, Public health, Injuries, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, GBD, risck factors, attributable burden of disease, 3142 Public health care science, environmental and occupational health, 3. Good health, Relative risk, Environmental health, Health, Hypertension, Global Burden of Diseases, Injuries, Risk Factors, A990 Medicine and Dentistry not elsewhere classified, Female, Leading risk factors, Global Health Metrics, Cohort study, Human, medicine.medical_specialty, Substance-Related Disorders, Population, UNITED-STATES, Risk Assessment, DIET, ITC-HYBRID, 03 medical and health sciences, Life Expectancy, MORTALITY, DISABILITY, POLLUTION, CLUSTERS, SDG 3 - Good Health and Well-being, General & Internal Medicine, medicine, Humans, Global Burden of Disease Study, Risk factor, education, Global burden, business.industry, Risk Factor, Malnutrition, Klinisk medicin, Global Burden of Diseases, Environmental Exposure, medicine.disease, Enfermedades, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Years of potential life lost, Socioeconomic Factors, Risk factors, Disease study, Hyperglycemia, ITC-ISI-JOURNAL-ARTICLE, NA, Clinical Medicine, business, RA
Abstract: Background Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk-outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk-outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk-outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10.8 million (95% uncertainty interval [UI] 9.51-12.1) deaths (19.2% [16.9-21.3] of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8.71 million (8.12-9.31) deaths (15.4% [14.6-16.2] of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253-350) DALYs (11.6% [10.3-13.1] of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0-9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10-24 years, alcohol use for those aged 25-49 years, and high systolic blood pressure for those aged 50-74 years and 75 years and older. Interpretation Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
Published: 2020

29. Characterization of clinically relevant copy-number variants from exomes of patients with inherited heart disease and unexplained sudden cardiac death

Author: Emma S, Singer, Samantha B, Ross, Jon R, Skinner, Robert G, Weintraub, Jodie, Ingles, Christopher, Semsarian, and Richard D, Bagnall
Subjects: Death, Sudden, Cardiac, DNA Copy Number Variations, Heart Diseases, Humans, Exome, Genetic Testing
Abstract: Copy-number variant (CNV) analysis is increasingly performed in genetic diagnostics. We leveraged recent gene curation efforts and technical standards for interpretation and reporting of CNVs to characterize clinically relevant CNVs in patients with inherited heart disease and sudden cardiac death.Exome sequencing data were analyzed for CNVs using eXome-Hidden Markov Model tool in 48 established disease genes. CNV breakpoint junctions were characterized. CNVs were classified using the American College of Medical Genetics and Genomics technical standards.We identified eight CNVs in 690 unrelated probands (1.2%). Characterization of breakpoint junctions revealed nonhomologous end joining was responsible for four deletions, whereas one duplication was caused by nonallelic homologous recombination between duplicated sequences in MYH6 and MYH7. Identifying the precise breakpoint junctions determined the genomic involvement and proved useful for interpreting the clinical relevance of CNVs. Three large deletions involving TTN, MYBPC3, and KCNH2 were classified as pathogenic in three patients. Haplotype analysis of a deletion in ACTN2, found in two families, suggests the deletion was caused by an ancestral event.CNVs infrequently cause inherited heart diseases and should be investigated when standard genetic testing does not reveal a genetic diagnosis.
Published: 2020

30. COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ)

Author: Christopher S. Hayward, Gayathri Kumarasinghe, David M. Kaye, Priya Nair, Robert N. Doughty, Jo-Dee L. Lattimore, Sean Lal, Lawrence Dembo, Leonard Kritharides, Paul G. Bannon, Nicole K. Bart, Peter S. Macdonald, Máté Rudas, John Atherton, Clara K Chow, Carmine G. De Pasquale, George Javorsky, Robert G. Weintraub, Craig P. Juergens, Peter Bergin, Richard Totaro, and Marcus Ilton
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, ARDS, Consensus, Circulatory collapse, Myocarditis, Targeted transthoracic echocardiogram, Critical Illness, Pneumonia, Viral, Cardiology, Cardiomyopathy, 030204 cardiovascular system & hematology, Article, Betacoronavirus, 03 medical and health sciences, 0302 clinical medicine, Intensive care, medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Acute cardiomyopathy, Pandemics, 1102 Cardiorespiratory Medicine and Haematology, 1117 Public Health and Health Services, Societies, Medical, Cause of death, Heart Failure, Infection Control, biology, SARS-CoV-2, business.industry, Australia, COVID-19, medicine.disease, Troponin, Patient Care Management, Coronavirus, Screening algorithm, Cardiovascular System & Hematology, Heart failure, biology.protein, Risk Adjustment, High sensitivity troponin, Coronavirus Infections, Cardiology and Cardiovascular Medicine, business, New Zealand
Abstract: Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.
Published: 2020

31. Comparison of Pulmonary Arterial Hypertension Risk Assessment Models Using the Pulmonary Hypertension Society of Australia and New Zealand Registry Cohort

Author: P. Steele, Carolyn Corrigan, David S. Celermajer, Mark Horrigan, Melanie Lavender, Robert G. Weintraub, Ken Whyte, Nathan Dwyer, Vivek Thakkar, James Anderson, Nicholas Collins, J Feenstra, Tanya McWilliams, Jeremy P. Wrobel, Dominic Keating, E Kotylar, Helen Whitford, Anne Keogh, Edmund M.T. Lau, G. Strange, Trevor Williams, and Bronwen Rhodes
Subjects: medicine.medical_specialty, business.industry, Emergency medicine, Cohort, medicine, Respiratory system, medicine.disease, business, Pulmonary hypertension, Hypertension risk
Published: 2020

32. Rare Association of an Intramural Coronary Artery and Truncus Arteriosus

Author: Yves d'Udekem, Igor E. Konstantinov, Robert G. Weintraub, Christian P. Brizard, and Phillip S. Naimo
Subjects: Pulmonary and Respiratory Medicine, Adult, Heart Defects, Congenital, Male, medicine.medical_specialty, Truncus Arteriosus, Fatal outcome, Heart disease, Coronary Vessel Anomalies, Coronary Vessel Anomaly, Persistent truncus arteriosus, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Fatal Outcome, Rare Diseases, Internal medicine, medicine, Humans, 030212 general & internal medicine, Cardiac Surgical Procedures, business.industry, Infant, Newborn, Infant, medicine.disease, Coronary Vessels, medicine.anatomical_structure, Echocardiography, Concomitant, Child, Preschool, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Artery
Abstract: The association of truncus arteriosus (TA) and an intramural coronary artery is rare. Seven (7) patients had TA and an intramural coronary artery at the Royal Children's Hospital, Melbourne between 1996 and 2018. Four (4) patients underwent concomitant unroofing of their intramural coronary artery. One (1) patient who did not undergo concomitant unroofing had a cardiac arrest on postoperative day 1 and subsequently underwent reoperation for coronary unroofing. Given the potential for serious complications, patients with TA and an intramural coronary artery may benefit from coronary unroofing with creation of a generous neo-ostium.
Published: 2020

33. Review of the impact of donor characteristics on pediatric heart transplant outcomes

Author: Matthew Fenton, Jennifer Conway, Richard Kirk, Jean A Ballweg, Maryanne Chrisant, Lara Danziger-Isakov, S.J. Kindel, Robert G. Weintraub, Oliver Meira, Anne I. Dipchand, and Ryan R. Davies
Subjects: medicine.medical_specialty, Adolescent, medicine.medical_treatment, Ischemic time, Organ transplantation, Donor Selection, medicine, Humans, Lung transplantation, In patient, Child, Intensive care medicine, Heart Failure, Heart transplantation, Transplantation, business.industry, Infant, Newborn, Infant, Treatment options, medicine.disease, Tissue Donors, Treatment Outcome, Child, Preschool, Heart failure, Pediatrics, Perinatology and Child Health, Heart Transplantation, business
Abstract: Heart transplantation (HTx) is a treatment option for end-stage heart failure in children. HTx is limited by the availability and acceptability of donor hearts. Refusal of donor hearts has been reported to be common with reasons for refusal including preexisting donor characteristics. This review will focus on the impact of donor characteristics and comorbidities on outcomes following pediatric HTx. A literature review was performed to identify articles on donor characteristics and comorbidities and pediatric HTx outcomes. There are many donor characteristics to consider when accepting a donor heart. Weight-based matching is the most common form of matching in pediatric HTx with a donor-recipient weight ratio between 0.7 and 3 having limited impact on outcomes. From an age perspective, donors
Published: 2020

34. Prospective Evaluation of the Utility of Whole Exome Sequencing in Dilated Cardiomyopathy

Author: Robert G. Weintraub, David L Hare, Mathew Wallis, Dominica Zentner, T. Thompson, Alison H. Trainer, Elly Lynch, Melissa Martyn, Michael Chetrit, Paul A. James, Jay Ramchand, D Phelan, Siobhan Lockwood, Omar Farouque, Belinda Chong, Ivan Macciocca, and Jitendra K. Vohra
Subjects: Adult, Cardiomyopathy, Dilated, Male, medicine.medical_specialty, Adolescent, Cost effectiveness, Cardiomyopathy, Genomics, 030204 cardiovascular system & hematology, Bioinformatics, whole exome sequencing, 03 medical and health sciences, Genetic Heterogeneity, Young Adult, 0302 clinical medicine, Predictive Value of Tests, Exome Sequencing, medicine, Genetics, Humans, Genetic Predisposition to Disease, Genetic Testing, Prospective Studies, clinical exome, Exome sequencing, 030304 developmental biology, Genetic testing, Original Research, next generation sequencing, 0303 health sciences, medicine.diagnostic_test, business.industry, Genetic heterogeneity, Genetic Variation, High-Throughput Nucleotide Sequencing, Dilated cardiomyopathy, Middle Aged, medicine.disease, Phenotype, Medical genetics, Female, Cardiology and Cardiovascular Medicine, business, cardiomyopathy
Abstract: Background Dilated cardiomyopathy may be heritable but shows extensive genetic heterogeneity. The utility of whole exome sequencing as a first‐line genetic test for patients with dilated cardiomyopathy in a contemporary “real‐world” setting has not been specifically established. Using whole exome sequencing with rigorous, evidence‐based variant interpretation, we aimed to identify the prevalence of a molecular diagnosis in patients with dilated cardiomyopathy in a clinical setting. Methods and Results Whole exome sequencing was performed in eligible patients (n=83) with idiopathic or familial dilated cardiomyopathy. Variants were prioritized for curation in up to 247 genes and classified using American College of Medical Genetics and Genomics–based criteria. Ten (12%) had a pathogenic or likely pathogenic variant. Eight (10%) participants had truncating TTN variants classified as variants of uncertain significance. Five (6%) participants had variants of unknown significance according to strict American College of Medical Genetics and Genomics criteria but classified as either pathogenic or likely pathogenic by other clinical laboratories. Pathogenic or likely pathogenic variants were found in 8 genes (all within tier 1 genes), 2 (20%) of which are not included in a standard commercially available dilated cardiomyopathy panel. Using our bioinformatics pipeline, there was an average of 0.74 variants of uncertain significance per case with ≈0.75 person‐hours needed to interpret each of these variants. Conclusions Whole exome sequencing is an effective diagnostic tool for patients with dilated cardiomyopathy. With stringent classification using American College of Medical Genetics and Genomics criteria, the rate of detection of pathogenic variants is lower than previous reports. Efforts to improve adherence to these guidelines will be important to prevent erroneous misclassification of nonpathogenic variants in dilated cardiomyopathy genetic testing and inappropriate cascade screening.
Published: 2020

35. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: Sorin Hostiuc, Shaun Wen Huey Lee, Jorge R. Ledesma, Carsten Flohr, Masoumeh Sadeghi, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Cyrus Alinia, Mehdi Bohluli, Félix Carvalho, Yun Jin Kim, Catalina Liliana Andrei, Seyyed Meysam Mousavi, Bernhard T. Baune, Ehsan Ahmadpour, Dinh-Toi Chu, Beatrix Haddock, Gianfranco Alicandro, Vasily Vlassov, Mohammad Taghi Khodayari, Gianna Gayle Herrera Amul, Arash Tehrani-Banihashemi, Govinda Prasad Dhungana, Fereshteh Ansari, Michael K. Hole, Azeem Majeed, Iman Halvaei, Saqib Ali, Arianna Maever L. Amit, Tomas Y. Yeheyis, John S. Ji, Martin McKee, Jamileh Shadid, Leonardo Roever, Peng Jia, Ettore Beghi, Pablo M. Lavados, Young Eun Kim, Vahid Alipour, Sowmya J. Rao, Ahmad Daryani, Cathleen Keller, Ibrahim Abdollahpour, Nicole K. DeCleene, Ebrahim Babaee, Saman Esmaeilnejad, Boris Bikbov, William M. Gardner, Lydia M. Haile, Luca Ronfani, Azalea M. Thomson, Irena Ilic, Ruth W. Kimokoti, Yingxi Zhao, Guoqing Hu, Mehran Shams-Beyranvand, Ilais Moreno Velásquez, Nathaniel J. Henry, Brijesh Sathian, Daniel Kim, Peter Memiah, Mohammad Hadi Abbasi, Andrea Farioli, Zahra Kamiab, Bolajoko O. Olusanya, Matthew C. Doxey, Tommi Vasankari, Hamideh Salimzadeh, Luisa Sorio Flor, Priya Rathi, Shanshan Li, Tanvir M. Huda, Dillon O Sylte, Rosario Cárdenas, Agegnehu Bante, Helen Ippolito, Alyssa Acebedo, Jeffrey D. Stanaway, Anwar Faraj, João Pedro Silva, Amin Mousavi Khaneghah, Pushpendra Kumar, Sangram Kishor Patel, Josephine W. Ngunjiri, Holly E. Erskine, Eugene Sobngwi, Filippo Ariani, Shane D. Morrison, Mohammad Aghaali, Meghan D. Mooney, Vera Marisa Costa, Palash Chandra Banik, Rupak Desai, Ken Takahashi, Maigeng Zhou, Morteza Oladnabi, Bogdan Oancea, Daniela Ribeiro, Mohammad Farahmand, Irmina Maria Michalek, Yetunde O. John-Akinola, Khem Narayan Pokhrel, Emilie R Maddison, Syed Mohamed Aljunid, Damian G. Hoy, Hosni Salem, V. 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S., Roberts, S., Robinson, S. R., Roever, L., Rolfe, S., Ronfani, L., Roshandel, G., Roth, G. A., Rubagotti, E., Rumisha, S. F., Sabour, S., Sachdev, P. S., Saddik, B., Sadeghi, E., Sadeghi, M., Saeidi, S., Safi, S., Safiri, S., Sagar, R., Sahebkar, A., Sahraian, M. A., Sajadi, S. M., Salahshoor, M. R., Salamati, P., Salehi Zahabi, S., Salem, H., Salem, M. R. R., Salimzadeh, H., Salomon, J. A., Salz, I., Samad, Z., Samy, A. M., Sanabria, J., Santomauro, D. F., Santos, I. S., Santos, J. V., Santric-Milicevic, M. M., Saraswathy, S. Y. I., Sarmiento-Suarez, R., Sarrafzadegan, N., Sartorius, B., Sarveazad, A., Sathian, B., Sathish, T., Sattin, D., Sbarra, A. N., Schaeffer, L. E., Schiavolin, S., Schmidt, M. I., Schutte, A. E., Schwebel, D. C., Schwendicke, F., Senbeta, A. M., Senthilkumaran, S., Sepanlou, S. G., Shackelford, K. A., Shadid, J., Shahabi, S., Shaheen, A. A., Shaikh, M. A., Shalash, A. 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A., Yeheyis, T. Y., Yeshitila, Y. G., Yip, P., Yonemoto, N., Yoon, S. -J., Yoosefi Lebni, J., Younis, M. Z., Younker, T. P., Yousefi, Z., Yousefifard, M., Yousefinezhadi, T., Yousuf, A. Y., Yu, C., Yusefzadeh, H., Zahirian Moghadam, T., Zaki, L., Zaman, S. B., Zamani, M., Zamanian, M., Zandian, H., Zangeneh, A., Zastrozhin, M. S., Zewdie, K. A., Zhang, Y., Zhang, Z. -J., Zhao, J. T., Zhao, Y., Zheng, P., Zhou, M., Ziapour, A., Zimsen, S. R. M., Naghavi, M., Murray, C. J. L., Department of Public Health, Clinicum, Department of Neurosciences, HUS Comprehensive Cancer Center, Environmental Sciences, Public Health, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Value, Affordability and Sustainability (VALUE), Microbes in Health and Disease (MHD), Sálfræðideild (HR), Department of Psychology (RU), Samfélagssvið (HR), School of Social Sciences (RU), Háskólinn í Reykjavík, Reykjavik University, GBD 2019 Diseases and Injuries Collaborator, Violante FS, Department of Earth Observation Science, Faculty of Geo-Information Science and Earth Observation, and UT-I-ITC-ACQUAL
Subjects: Male, Life expectancy, Disability-Adjusted Life Year, Diseases, Disease, communicable disease, systematic analysis, Global Burden of Disease, 0302 clinical medicine, 80 and over, Medicine, 10. No inequality, Child, 11 Medical and Health Sciences, injuries, Aged, 80 and over, education.field_of_study, Sjúkdómar, DEMENTIA, FALLS, General Medicine, Forvarnir, 3. Good health, Child, Preschool, Human, GBD, Population health, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Humans, Global Burden of Disease Study, education, Aged, Spatial Analysis, Global burden, Disability, Prevention, DISABILITY, Infant, Spatial Analysi, Mortality rate, Global Burden of Disease, Diseases, Injuries, Systematic analysis, PREVENTION, Years of potential life lost, Risk factors, Disease study, ITC-ISI-JOURNAL-ARTICLE, RISK-FACTORS, Clinical Medicine, RA, Demography, Fötlun, Dánartíðni, Áhættuþættir, 030204 cardiovascular system & hematology, Risk Factors, Cause of Death, Global health, 030212 general & internal medicine, 1. No poverty, Disability-Adjusted Life Years, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, 3142 Public health care science, environmental and occupational health, Adolescent, Adult, Age Distribution, Female, Infant, Newborn, Young Adult, Lýðheilsa, CLINICAL-TRIALS, Population, Settore MED/01 - Statistica Medica, diseases, ITC-HYBRID, Heilbrigðisvísindi, General & Internal Medicine, Mortality, Preschool, Disease burden, business.industry, Risk Factor, Klinisk medicin, Newborn, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Áverkar, Systematic analysis, NA, business
Abstract: Publisher's version (útgefin grein), Background In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd., Research reported in this publication was supported by the Bill & Melinda Gates Foundation; the University of Melbourne; Queensland Department of Health, Australia; the National Health and Medical Research Council, Australia; Public Health England; the Norwegian Institute of Public Health; St Jude Children's Research Hospital; the Cardiovascular Medical Research and Education Fund; the National Institute on Ageing of the National Institutes of Health (award P30AG047845); and the National Institute of Mental Health of the National Institutes of Health (award R01MH110163). The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The authors alone are responsible for the views expressed in this Article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the National Health Service (NHS), the National Institute for Health Research (NIHR), the UK Department of Health and Social Care, or Public Health England; the United States Agency for International Development (USAID), the US Government, or MEASURE Evaluation; or the European Centre for Disease Prevention and Control (ECDC). This research used data from the Chile National Health Survey 2003, 2009-10, and 2016-17. The authors are grateful to the Ministry of Health, the survey copyright owner, for allowing them to have the database. All results of the study are those of the authors and in no way committed to the Ministry. The Costa Rican Longevity and Healthy Aging Study project is a longitudinal study by the University of Costa Rica's Centro Centroamericano de Poblacion and Instituto de Investigaciones en Salud, in collaboration with the University of California at Berkeley. The original pre-1945 cohort was funded by the Wellcome Trust (grant 072406), and the 1945-55 Retirement Cohort was funded by the US National Institute on Aging (grant R01AG031716). The principal investigators are Luis Rosero-Bixby and William H Dow and co-principal investigators are Xinia Fernandez and Gilbert Brenes. The accuracy of the authors' statistical analysis and the findings they report are not the responsibility of ECDC. ECDC is not responsible for conclusions or opinions drawn from the data provided. ECDC is not responsible for the correctness of the data and for data management, data merging and data collation after provision of the data. ECDC shall not be held liable for improper or incorrect use of the data. The Health Behaviour in School-Aged Children (HBSC) study is an international study carried out in collaboration with WHO/EURO. The international coordinator of the 1997-98, 2001-02, 2005-06, and 2009-10 surveys was Candace Currie and the databank manager for the 1997-98 survey was Bente Wold, whereas for the following surveys Oddrun Samdal was the databank manager. A list of principal investigators in each country can be found on the HBSC website. Data used in this paper come from the 2009-10 Ghana Socioeconomic Panel Study Survey, which is a nationally representative survey of more than 5000 households in Ghana. The survey is a joint effort undertaken by the Institute of Statistical, Social and Economic Research (ISSER) at the University of Ghana and the Economic Growth Centre (EGC) at Yale University. It was funded by EGC. ISSER and the EGC are not responsible for the estimations reported by the analysts. The Palestinian Central Bureau of Statistics granted the researchers access to relevant data in accordance with license number SLN2014-3-170, after subjecting data to processing aiming to preserve the confidentiality of individual data in accordance with the General Statistics Law, 2000. The researchers are solely responsible for the conclusions and inferences drawn upon available data. Data for this research was provided by MEASURE Evaluation, funded by USAID. The authors thank the Russia Longitudinal Monitoring Survey, conducted by the National Research University Higher School of Economics and ZAO Demoscope together with Carolina Population Center, University of North Carolina at Chapel Hill and the Institute of Sociology, Russia Academy of Sciences for making data available. This paper uses data from the Bhutan 2014 STEPS survey, implemented by the Ministry of Health with the support of WHO; the Kuwait 2006 and 2014 STEPS surveys, implemented by the Ministry of Health with the support of WHO; the Libya 2009 STEPS survey, implemented by the Secretariat of Health and Environment with the support of WHO; the Malawi 2009 STEPS survey, implemented by Ministry of Health with the support of WHO; and the Moldova 2013 STEPS survey, implemented by the Ministry of Health, the National Bureau of Statistics, and the National Center of Public Health with the support of WHO. This paper uses data from Survey of Health, Ageing and Retirement in Europe (SHARE) Waves 1 (DOI:10.6103/SHARE. w1.700), 2 (10.6103/SHARE.w2.700), 3 (10.6103/SHARE.w3.700), 4 (10.6103/SHARE.w4.700), 5 (10.6103/SHARE.w5.700), 6 (10.6103/SHARE.w6.700), and 7 (10.6103/SHARE.w7.700); see Borsch-Supan and colleagues (2013) for methodological details. The SHARE data collection has been funded by the European Commission through FP5 (QLK6-CT-2001-00360), FP6 (SHARE-I3: RII-CT-2006-062193, COMPARE: CIT5-CT-2005-028857, SHARELIFE: CIT4-CT-2006-028812), FP7 (SHARE-PREP: GA N degrees 211909, SHARE-LEAP: GA N degrees 227822, SHARE M4: GA N degrees 261982) and Horizon 2020 (SHARE-DEV3: GA N degrees 676536, SERISS: GA N degrees 654221) and by DG Employment, Social Affairs & Inclusion. Additional funding from the German Ministry of Education and Research, the Max Planck Society for the Advancement of Science, the US National Institute on Aging (U01_AG09740-13S2, P01_AG005842, P01_AG08291, P30_AG12815, R21_AG025169, Y1-AG-4553-01, IAG_BSR06-11, OGHA_04-064, HHSN271201300071C), and from various national funding sources is gratefully acknowledged. This study has been realised using the data collected by the Swiss Household Panel, which is based at the Swiss Centre of Expertise in the Social Sciences. The project is financed by the Swiss National Science Foundation. The United States Aging, Demographics, and Memory Study is a supplement to the Health and Retirement Study (HRS), which is sponsored by the National Institute of Aging (grant number NIA U01AG009740). It was conducted jointly by Duke University and the University of Michigan. The HRS is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan. This paper uses data from Add Health, a program project designed by J Richard Udry, Peter S Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website. No direct support was received from grant P01-HD31921 for this analysis. The data reported here have been supplied by the United States Renal Data System. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US Government. Collection of data for the Mozambique National Survey on the Causes of Death 2007-08 was made possible by USAID under the terms of cooperative agreement GPO-A-00-08-000_D3-00. This manuscript is based on data collected and shared by the International Vaccine Institute (IVI) from an original study IVI conducted. L G Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (Brazil; finance code 001) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, a Brazilian funding agency). I N Ackerman was supported by a Victorian Health and Medical Research Fellowship awarded by the Victorian Government. O O Adetokunboh acknowledges the South African Department of Science and Innovation and the National Research Foundation. A Agrawal acknowledges the Wellcome Trust DBT India Alliance Senior Fellowship. S M Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. M Ausloos, C Herteliu, and A Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. A Badawi is supported by the Public Health Agency of Canada. D A Bennett was supported by the NIHR Oxford Biomedical Research Centre. R Bourne acknowledges the Brien Holden Vision Institute, University of Heidelberg, Sightsavers, Fred Hollows Foundation, and Thea Foundation. G B Britton and I Moreno Velasquez were supported by the Sistema Nacional de Investigacion, SNI-SENACYT, Panama. R Buchbinder was supported by an Australian National Health and Medical Research Council (NHMRC) Senior Principal Research Fellowship. J J Carrero was supported by the Swedish Research Council (2019-01059). F Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. A R Chang was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases grant K23 DK106515. V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundacao para a Ciencia e Tecnologia, IP, under the Norma Transitaria DL57/2016/CP1334/CT0006. A Douiri acknowledges support and funding from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South London at King's College Hospital NHS Foundation Trust and the Royal College of Physicians, and support from the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. B B Duncan acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. H E Erskine is the recipient of an Australian NHMRC Early Career Fellowship grant (APP1137969). A J Ferrari was supported by a NHMRC Early Career Fellowship grant (APP1121516). H E Erskine and A J Ferrari are employed by and A M Mantilla-Herrera and D F Santomauro affiliated with the Queensland Centre for Mental Health Research, which receives core funding from the Queensland Department of Health. M L Ferreira holds an NHMRC Research Fellowship. C Flohr was supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust. M Freitas acknowledges financial support from the EU (European Regional Development Fund [FEDER] funds through COMPETE POCI-01-0145-FEDER-029248) and National Funds (Fundacao para a Ciencia e Tecnologia) through project PTDC/NAN-MAT/29248/2017. A L S Guimaraes acknowledges support from CNPq. C Herteliu was partially supported by a grant co-funded by FEDER through Operational Competitiveness Program (project ID P_40_382). P Hoogar acknowledges Centre for Bio Cultural Studies, Directorate of Research, Manipal Academy of Higher Education and Centre for Holistic Development and Research, Kalaghatagi. F N Hugo acknowledges the Visiting Professorship, PRINT Program, CAPES Foundation, Brazil. B-F Hwang was supported by China Medical University (CMU107-Z-04), Taichung, Taiwan. S M S Islam was funded by a National Heart Foundation Senior Research Fellowship and supported by Deakin University. R Q Ivers was supported by a research fellowship from the National Health and Medical Research Council of Australia. M Jakovljevic acknowledges the Serbian part of this GBD-related contribution was co-funded through Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. P Jeemon was supported by a Clinical and Public Health intermediate fellowship (grant number IA/CPHI/14/1/501497) from the Wellcome Trust-Department of Biotechnology, India Alliance (2015-20). O John is a recipient of UIPA scholarship from University of New South Wales, Sydney. S V Katikireddi acknowledges funding from a NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_12017/13, MC_UU_12017/15), and the Scottish Government Chief Scientist Office (SPHSU13, SPHSU15). C Kieling is a CNPq researcher and a UK Academy of Medical Sciences Newton Advanced Fellow. Y J Kim was supported by Research Management Office, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/00010). K Krishan is supported by UGC Centre of Advanced Study awarded to the Department of Anthropology, Panjab University, Chandigarh, India. M Kumar was supported by K43 TW 010716 FIC/NIMH. B Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. J V Lazarus was supported by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III [ISCIII]/ESF, the EU [CP18/00074]). K J Looker thanks the NIHR Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England, for research support. S Lorkowski was funded by the German Federal Ministry of Education and Research (nutriCARD, grant agreement number 01EA1808A). R A Lyons is supported by Health Data Research UK (HDR-9006), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, NIHR (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome Trust. J J McGrath is supported by the Danish National Research Foundation (Niels Bohr Professorship), and the Queensland Health Department (via West Moreton HHS). P T N Memiah acknowledges support from CODESRIA. U O Mueller gratefully acknowledges funding by the German National Cohort Study BMBF grant number 01ER1801D. S Nomura acknowledges the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). A Ortiz was supported by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. S B Patten was supported by the Cuthbertson & Fischer Chair in Pediatric Mental Health at the University of Calgary. G C Patton was supported by an aNHMRC Senior Principal Research Fellowship. M R Phillips was supported in part by the National Natural Science Foundation of China (NSFC, number 81371502 and 81761128031). A Raggi, D Sattin, and S Schiavolin were supported by grants from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4-Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). P Rathi and B Unnikrishnan acknowledge Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. A L P Ribeiro was supported by Brazilian National Research Council, CNPq, and the Minas Gerais State Research Agency, FAPEMIG. D C Ribeiro was supported by The Sir Charles Hercus Health Research Fellowship (#18/111) Health Research Council of New Zealand. D Ribeiro acknowledges financial support from the EU (FEDER funds through the Operational Competitiveness Program; POCI-01-0145-FEDER-029253). P S Sachdev acknowledges funding from the NHMRC of Australia Program Grant. A M Samy was supported by a fellowship from the Egyptian Fulbright Mission Program. M M Santric-Milicevic acknowledges the Ministry of Education, Science and Technological Development of the Republic of Serbia (contract number 175087). R Sarmiento-Suarez received institutional support from Applied and Environmental Sciences University (Bogota, Colombia) and ISCIII (Madrid, Spain). A E Schutte received support from the South African National Research Foundation SARChI Initiative (GUN 86895) and Medical Research Council. S T S Skou is currently funded by a grant from Region Zealand (Exercise First) and a grant from the European Research Council under the EU's Horizon 2020 research and innovation program (grant agreement number 801790). J B Soriano is funded by Centro de Investigacion en Red de Enfermedades Respiratorias, ISCIII. R Tabares-Seisdedos was supported in part by the national grant PI17/00719 from ISCIII-FEDER. N Taveira was partially supported by the European & Developing Countries Clinical Trials Partnership, the EU (LIFE project, reference RIA2016MC-1615). S Tyrovolas was supported by the Foundation for Education and European Culture, the Sara Borrell postdoctoral programme (reference number CD15/00019 from ISCIII-FEDER). S B Zaman received a scholarship from the Australian Government research training programme in support of his academic career., "Peer Reviewed"
Published: 2020

36. Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Author: William M. Gardner, Rawlance Ndejjo, Govinda Prasad Dhungana, Fereshteh Ansari, Kathleen Pillsbury Hopf, João Pedro Silva, M. Mofizul Islam, Cong Zhu, Abdul Hafiz, Irmina Maria Michalek, Syed Mohamed Aljunid, Leonardo Roever, Mustefa Glagn, Davood Anvari, Tessa M. Pilz, Sameer Vali Gopalani, Joel M. Francis, Man Mohan Mehndiratta, Rakhi Dandona, Abbas Sheikhtaheri, Mansour Ghafourifard, Simon Øverland, David Laith Rawaf, Jaykaran Charan, Akram Pourshams, Mostafa Dianatinasab, Morteza Mahmoudi, Alton Lu, Alyssa N. Sbarra, Lorainne Tudor Car, Franz Castro, Hafiz Ansar Rasul Suleria, Luca Ronfani, Marina Pinheiro, Mehran Asadi-Aliabadi, Maziar Moradi-Lakeh, Hoa Thi Do, Whitney L. Teagle, Sofia Androudi, Carl Abelardo T. Antonio, Myron Anthony Godinho, Bhaskaran Unnikrishnan, Oluchi Ezekannagha, Getinet Ayano, Seyyed Shamsadin Athari, Dimas Ria Angga Pribadi, Kyle E. Simpson, Muluken Bekele Sorrie, Vivekanand Jha, Chukwuma David Umeokonkwo, Akshaya Srikanth Bhagavathula, Cuong Tat Nguyen, Amr Hassan, Akine Eshete Abosetugn, Hailay Abrha Gesesew, Anna V. Korotkova, Brijesh Sathian, Marcello Tonelli, Olatunde Aremu, Mohammad Reza Salahshoor, Juan Jesus Carrero, Cameron J. Kneib, Ravi Prakash Jha, David H. Shaw, Hossein Samadi Kafil, Tanuj Kanchan, Khezar Hayat, Hamid Sharifi, Morteza Shamsizadeh, Muktar Omer Omer, Fatemeh Amiri, Hamidreza Pazoki Toroudi, David Edvardsson, Xiu Ju George Zhao, Hannah Han, Leticia Avila-Burgos, Adam E. Berman, Jemal Abdu Mohammed, Thomas Pilgrim, Leila Doshmangir, Mu'awiyyah Babale Sufiyan, David M. Pigott, Hadi Hassankhani, Beatriz Paulina Ayala Quintanilla, Teklemariam Gultie, Arash Ziapour, Seyed Sina Naghibi Irvani, Ilse N. Dippenaar, Jean Jacques Noubiap, Emmanuela Gakidou, Abiyu Mekonnen Gebrehiwot, Maha El Tantawi, Xuefeng Liu, Zulfiqar A. Bhutta, Keyghobad Ghadiri, João Mauricio Castaldelli-Maia, Behzad Karami Matin, Yunquan Zhang, Vera Marisa Costa, Iyad Sultan, Mostafa Hosseini, Abdulaziz Khalid Abu Haimed, Haidong Wang, Kaleab Alemayehu Zewdie, Celine M. Barthelemy, Hosna Janjani, Bartosz Miazgowski, Jobert Richie Nansseu, Arianna Maever L. Amit, John S. Ji, Ata Rafiee, Maria Inês Schmidt, Alireza Rafiei, Somayeh Bohlouli, Joana Morgado-da-Costa, Huong Lan Thi Nguyen, Pradyumna Agasthi, Tiffany K. Gill, Martin McKee, Khaled Khatab, Jae Il Shin, Animut Tagele Tamiru, Giancarlo Logroscino, Hassan Abolhassani, Syed Saoud Zaidi, Sivan Yegnanarayana Iyer Saraswathy, Garumma Tolu Feyissa, Ahmad Daryani, Ziyad Al-Aly, Gebreamlak Gebremedhn Gebremeskel, Michael T. Chung, Amirhossein Sahebkar, Mehedi Hasan, Saeed Shahabi, Diep Ngoc Nguyen, Yohannes Kinfu, Nicholas L S Roberts, Jagadish Rao Padubidri, Mika Shigematsu, Lucero Cahuana-Hurtado, Deepa Jahagirdar, Islam Y. Elgendy, Erkin M. Mirrakhimov, Tanvir M. Huda, Fakher Rahim, Dara K. Mohammad, Yingxi Zhao, Ruxandra Irina Negoi, Vinod C. Nayak, Reinhard Busse, Andrew T. Leever, Muhammad Aziz Rahman, Kathryn Mei Ming Lau, Stefania Mondello, Vivian Chia-Rong Hsieh, Kris J. Krohn, Reza Rawassizadeh, Vishnu Renjith, Jianing Ma, Moses K. Muriithi, Mark G. Shrime, Mayowa O. Owolabi, Nobuyuki Horita, Seyed Hossein Yahyazadeh Jabbari, Daniel Y. Cho, Miloje Savic, Moslem Soofi, Iqbal R. F. Elyazar, Freweini Gebrearegay G. Tela, Jonathan F. Mosser, Palash Chandra Banik, Andre Rodrigues Duraes, Yuan-Pang Wang, Natalie C. Galles, Rashid Abdi Guled, Abdallah M. Samy, Hadi Pourjafar, Roman Topor-Madry, Ayesha Humayun, Leila Zaki, Nuworza Kugbey, Maryam Khayamzadeh, Naznin Hossain, Jiregna Darega Gela, Jordi Alonso, Ruth W Kimokoti, A. A. Fomenkov, Jalal Arabloo, Aletta E. Schutte, Biruk Wogayehu Taddele, Teklehaimanot Gereziher Haile, Diego Augusto Santos Silva, Seyed Mohammad Kazem Aghamir, Maciej Banach, Deanna Anderlini, Moses J. Bockarie, Saleem Muhammad Rana, Randah R. Hamadeh, Farhad Islami, Olalekan A. Uthman, S. Mohammad Sajadi, Francisco Rogerlândio Martins-Melo, Shankar M Bakkannavar, Kairat Davletov, Soraya Seedat, Alan D. Lopez, Masoud Behzadifar, Benjamin B. Massenburg, Santosh Varughese, Ingan Ukur Tarigan, Amin Soheili, Félix Carvalho, Yun Jin Kim, Catalina Liliana Andrei, Caleb Mackay Salpeter Irvine, Mojgan Gitimoghaddam, G Anil Kumar, Rasmus J. Havmoeller, Hiroyasu Iso, Atte Meretoja, Yasir Waheed, João M. Furtado, Christian Razo, Neeti Kapoor, Mowafa Househ, Rajaa Al-Raddadi, Mohammad Khammarnia, Santi Martini, Feng Sha, Marco Vacante, Jacek A. Kopec, Hunduma Amensisa Bojia, Jacob Olusegun Olusanya, Kate E. LeGrand, Nikolay Ivanovich Briko, Robert S. Bernstein, Arun Balachandran, Davoud Adham, Ahad Bakhtiari, Shafiu Mohammed, Leake G. Gebremeskel, Smita Pakhale, Ejaz Ahmad Khan, Daniel Cury Ribeiro, Yousef Mohammad, Bernhard T. 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Morrison, Inga Dora Sigfusdottir, Marcel Ausloos, Mehdi Hosseinzadeh, Marcos Roberto Tovani-Palone, K M Shivakumar, Alireza Ansari-Moghaddam, Archith Boloor, Aidin Abedi, Binyam Minuye Birihane, Mohammad Ali Mansournia, Nihad A. Almasri, Simachew Animen Bante, Carlo Eduardo Medina-Solís, Leeberk Raja Inbaraj, Edgar Denova-Gutiérrez, Antonio Biondi, Valentin Yurievich Skryabin, Srinivasa Vittal Katikireddi, Sarika Chaturvedi, Francesco Saverio Violante, Abhay Gaidhane, George A. Mensah, Naohiro Yonemoto, Ahmad Ghashghaee, Ebrahim Babaee, Saman Esmaeilnejad, Sharath Burugina Nagaraja, Avina Vongpradith, Javad Nazari, Amir Khater, Michael K. 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Subjects: Index (economics), Servicios de Salud, SUSTAINABLE DEVELOPMENT GOALS, 030204 cardiovascular system & hematology, universal health coverage, sustaibale develpment goal, global burden of disease, performance, systematic analysis, Global Burden of Disease, 0302 clinical medicine, Universal Health Insurance, RA0421, 11. Sustainability, Per capita, Medical economics, Disease, 030212 general & internal medicine, 10. No inequality, 11 Medical and Health Sciences, effective coverage of health services, GBD 2019 Universal Health Coverage Collaborators, education.field_of_study, Public health, Medical care, Sjúkdómar, 4. Education, 1. No poverty, Health coverage, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Hälsovetenskaper, 3142 Public health care science, environmental and occupational health, Health services, 3. Good health, Global burden of disease, Health Expenditures, Humans, World Health Organization, Purchasing power parity, Scale (social sciences), Lýðheilsa, universal health coverag, CANCER SURVIVAL, ACCESS, Human, Heilsuhagfræði, medicine.medical_specialty, Health coverage, GBD, GBD, Universal health, GBD 2019, Population, Health expenditures, 3122 Cancers, Population health, 03 medical and health sciences, Health systems, Heilbrigðisvísindi, SDG 3 - Good Health and Well-being, General & Internal Medicine, Development economics, Health Sciences, medicine, Heilbrigðisstefna, Alþjóðaheilbrigðisstofnunin, QUALITY, Global Burden of Disease Study, education, PROGRESS, Disease burden, Health services accessibility, CARE, Heilbrigðisþjónusta, purl.org/pe-repo/ocde/ford#3.02.00 [https], Health Expenditure, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 3121 General medicine, internal medicine and other clinical medicine, Morbility, Administración de los Servicios de Salud, Medical policy, Business, Heilbrigðiskerfi
Abstract: Publisher's version (útgefin grein), Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (>= 65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0-100 based on the 2.5th and 97.5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target-1 billion more people benefiting from UHC by 2023-we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45.8 (95% uncertainty interval 44.2-47.5) in 1990 to 60.3 (58.7-61.9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2.6% [1.9-3.3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010-2019 relative to 1990-2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0.79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388.9 million (358.6-421.3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3.1 billion (3.0-3.2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968.1 million [903.5-1040.3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people-the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close-or how far-all populations are in benefiting from UHC., Lucas Guimaraes Abreu acknowledges support from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (Capes) -Finance Code 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) and Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG). Olatunji O Adetokunboh acknowledges South African Department of Science & Innovation, and National Research Foundation. Anurag Agrawal acknowledges support from the Wellcome Trust DBT India Alliance Senior Fellowship IA/CPHS/14/1/501489. Rufus Olusola Akinyemi acknowledges Grant U01HG010273 from the National Institutes of Health (NIH) as part of the H3Africa Consortium. Rufus Olusola Akinyemi is further supported by the FLAIR fellowship funded by the UK Royal Society and the African Academy of Sciences. Syed Mohamed Aljunid acknowledges the Department of Health Policy and Management, Faculty of Public Health, Kuwait University and International Centre for Casemix and Clinical Coding, Faculty of Medicine, National University of Malaysia for the approval and support to participate in this research project. Marcel Ausloos, Claudiu Herteliu, and Adrian Pana acknowledge partial support by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDSUEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Till Winfried Barnighausen acknowledges support from the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. Juan J Carrero was supported by the Swedish Research Council (2019-01059). Felix Carvalho acknowledges UID/MULTI/04378/2019 and UID/QUI/50006/2019 support with funding from FCT/MCTES through national funds. Vera Marisa Costa acknowledges support from grant (SFRH/BHD/110001/2015), received by Portuguese national funds through Fundacao para a Ciencia e a Tecnologia (FCT), IP, under the Norma TransitA3ria DL57/2016/CP1334/CT0006. Jan-Walter De Neve acknowledges support from the Alexander von Humboldt Foundation. Kebede Deribe acknowledges support by Wellcome Trust grant number 201900/Z/16/Z as part of his International Intermediate Fellowship. Claudiu Herteliu acknowledges partial support by a grant co-funded by European Fund for Regional Development through Operational Program for Competitiveness, Project ID P_40_382. Praveen Hoogar acknowledges the Centre for Bio Cultural Studies (CBiCS), Manipal Academy of Higher Education(MAHE), Manipal and Centre for Holistic Development and Research (CHDR), Kalghatgi. Bing-Fang Hwang acknowledges support from China Medical University (CMU108-MF-95), Taichung, Taiwan. Mihajlo Jakovljevic acknowledges the Serbian part of this GBD contribution was co-funded through the Grant OI175014 of the Ministry of Education Science and Technological Development of the Republic of Serbia. Aruna M Kamath acknowledges funding from the National Institutes of Health T32 grant (T32GM086270). Srinivasa Vittal Katikireddi acknowledges funding from the Medical Research Council (MC_UU_12017/13 & MC_UU_12017/15), Scottish Government Chief Scientist Office (SPHSU13 & SPHSU15) and an NRS Senior Clinical Fellowship (SCAF/15/02). Yun Jin Kim acknowledges support from the Research Management Centre, Xiamen University Malaysia (XMUMRF/2018-C2/ITCM/0001). Kewal Krishan acknowledges support from the DST PURSE grant and UGC Center of Advanced Study (CAS II) awarded to the Department of Anthropology, Panjab University, Chandigarh, India. Manasi Kumar acknowledges support from K43 TW010716 Fogarty International Center/NIMH. Ben Lacey acknowledges support from the NIHR Oxford Biomedical Research Centre and the BHF Centre of Research Excellence, Oxford. Ivan Landires is a member of the Sistema Nacional de InvestigaciA3n (SNI), which is supported by the Secretaria Nacional de Ciencia Tecnologia e Innovacion (SENACYT), Panama. Jeffrey V Lazarus acknowledges support by a Spanish Ministry of Science, Innovation and Universities Miguel Servet grant (Instituto de Salud Carlos III/ESF, European Union [CP18/00074]). Peter T N Memiah acknowledges CODESRIA; HISTP. Subas Neupane acknowledges partial support from the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital. Shuhei Nomura acknowledges support from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (18K10082). Alberto Ortiz acknowledges support by ISCIII PI19/00815, DTS18/00032, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, FRIAT, Comunidad de Madrid B2017/BMD-3686 CIFRA2-CM. These funding sources had no role in the writing of the manuscript or the decision to submit it for publication. George C Patton acknowledges support from a National Health & Medical Research Council Fellowship. Marina Pinheiro acknowledges support from FCT for funding through program DL 57/2016 -Norma transitA3ria. Alberto Raggi, David Sattin, and Silvia Schiavolin acknowledge support by a grant from the Italian Ministry of Health (Ricerca Corrente, Fondazione Istituto Neurologico C Besta, Linea 4 -Outcome Research: dagli Indicatori alle Raccomandazioni Cliniche). Daniel Cury Ribeiro acknowledges support from the Sir Charles Hercus Health Research Fellowship -Health Research Council of New Zealand (18/111). Perminder S Sachdev acknowledges funding from the NHMRC Australia. Abdallah M Samy acknowledges support from a fellowship from the Egyptian Fulbright Mission Program. Milena M Santric-Milicevic acknowledges support from the Ministry of Education, Science and Technological Development of the Republic of Serbia (Contract No. 175087). Rodrigo Sarmiento-Suarez acknowledges institutional support from University of Applied and Environmental Sciences in Bogota, Colombia, and Carlos III Institute of Health in Madrid, Spain. Maria Ines Schmidt acknowledges grants from the Foundation for the Support of Research of the State of Rio Grande do Sul (IATS and PrInt) and the Brazilian Ministry of Health. Sheikh Mohammed Shariful Islam acknowledges a fellowship from the National Heart Foundation of Australia and Deakin University. Aziz Sheikh acknowledges support from Health Data Research UK. Kenji Shibuya acknowledges Japan Ministry of Education, Culture, Sports, Science and Technology. Joan B Soriano acknowledges support by Centro de Investigacion en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Rafael Tabares-Seisdedos acknowledges partial support from grant PI17/00719 from ISCIII-FEDER. Santosh Kumar Tadakamadla acknowledges support from the National Health and Medical Research Council Early Career Fellowship, Australia. Marcello Tonelli acknowledges the David Freeze Chair in Health Services Research at the University of Calgary, AB, Canada., "Peer Reviewed"
Published: 2020

37. Global, regional, and national burden of congenital heart disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Author: Manisha Dubey, Michelle Echko, Mohamad-Hani Temsah, Craig Sable, Jean Jacques Noubiap, Ashish Awasthi, Nicholas J Kassebaum, Lemma Negesa, Molly R Nixon, Cuong Tat Nguyen, Paolo Cortesi, Anita Kar, Gene F. Kwan, Helen E Olsen, Emmanuel Peprah, Ionut Negoi, Trang Huyen Nguyen, Nu Thi Truong, Zoubida Zaidi, Samer Hamidi, Huong Lan Thi Nguyen, Robert G. Weintraub, Simon I. Hay, Christopher Hugo-Hamman, Mohsen Naghavi, Bach Xuan Tran, Lauren B. Wilner, Kathy J. Jenkins, Bistra Zheleva, Tung Thanh Tran, Ali H. Mokdad, Gregory A. Roth, Hagos Tasew Atalay, Shanti Patel, Ibrahim A Khalil, Kidu Gidey Weldegwergs, Son Hoang Nguyen, Marcos Roberto Tovani-Palone, Gerard R. Martin, Liesl Zühlke, Alison Smith, Zulfiqar A Bhutta, Jeffrey A. Towbin, Florian Fischer, Meghan S. Zimmerman, Jackie Lee Anne Boucher, Raman Krishna Kumar, Theo Vos, Long Hoang Nguyen, Chi Linh Hoang, Christopher J L Murray, Robert Reiner, Franz Castro, Kia Vosoughi, Ruxandra Irina Negoi, Desalegn Tadese Mengistu, Zimmerman, M, Smith, A, Sable, C, Echko, M, Wilner, L, Olsen, H, Atalay, H, Awasthi, A, Bhutta, Z, Boucher, J, Castro, F, Cortesi, P, Dubey, M, Fischer, F, Hamidi, S, Hay, S, Hoang, C, Hugo-Hamman, C, Jenkins, K, Kar, A, Khalil, I, Kumar, R, Kwan, G, Mengistu, D, Mokdad, A, Naghavi, M, Negesa, L, Negoi, I, Negoi, R, Nguyen, C, Nguyen, H, Nguyen, L, Nguyen, S, Nguyen, T, Nixon, M, Noubiap, J, Patel, S, Peprah, E, Reiner, R, Roth, G, Temsah, M, Tovani-Palone, M, Towbin, J, Tran, B, Tran, T, Truong, N, Vos, T, Vosoughi, K, Weintraub, R, Weldegwergs, K, Zaidi, Z, Zheleva, B, Zuhlke, L, Murray, C, Martin, G, and Kassebaum, N
Subjects: Heart Defects, Congenital, Pediatrics, medicine.medical_specialty, Adolescent, Heart disease, MED/42 - IGIENE GENERALE E APPLICATA, Psychological intervention, Burden, Global Health, Global Burden of Disease, 03 medical and health sciences, 0302 clinical medicine, Quality of life, 030225 pediatrics, Ductus arteriosus, Prevalence, Developmental and Educational Psychology, medicine, Humans, epidemiology, Disabled Persons, 030212 general & internal medicine, Child, Cause of death, Congenital Heart disease, business.industry, Infant, Newborn, Infant, Articles, medicine.disease, mortality, prevalnce, years lived with disability, medicine.anatomical_structure, Great vessels, Ventricle, Child, Preschool, Pediatrics, Perinatology and Child Health, Life course approach, business, Systematic Reviews as Topic
Abstract: Background: Previous congenital heart disease estimates came from few data sources, were geographically narrow, and did not evaluate congenital heart disease throughout the life course. Completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, this study aimed to provide comprehensive estimates of congenital heart disease mortality, prevalence, and disability by age for 195 countries and territories from 1990 to 2017. Methods: Mortality estimates were generated for aggregate congenital heart disease and non-fatal estimates for five subcategories (single ventricle and single ventricle pathway congenital heart anomalies; severe congenital heart anomalies excluding single ventricle heart defects; critical malformations of great vessels, congenital valvular heart disease, and patent ductus arteriosus; ventricular septal defect and atrial septal defect; and other congenital heart anomalies), for 1990 through to 2017. All available global data were systematically analysed to generate congenital heart disease mortality estimates (using Cause of Death Ensemble modelling) and prevalence estimates (DisMod-MR 2·1). Systematic literature reviews of all types of congenital anomalies to capture information on prevalence, associated mortality, and long-term health outcomes on congenital heart disease informed subsequent disability estimates. Findings: Congenital heart disease caused 261 247 deaths (95% uncertainty interval 216 567–308 159) globally in 2017, a 34·5% decline from 1990, with 180 624 deaths (146 825–214 178) being among infants (aged
Published: 2020

38. Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood

Author: Tibor Schuster, Robert N. Justo, Lynn A. Sleeper, Steven D. Colan, Christopher Semsarian, Alan Nugent, Andrew M. Davis, Gary F. Sholler, Katherine J Lee, Robert G. Weintraub, Piers E.F. Daubeney, Ingrid King, J. Ramsay, Terry Robertson, Peta M. A. Alexander, and Christian Turner
Subjects: Male, Time Factors, Health Status, Cardiomyopathy, 030204 cardiovascular system & hematology, Left ventricular hypertrophy, Pediatric and congenital heart disease, including cardiovascular surgery, 0302 clinical medicine, Risk Factors, Interquartile range, National Australian Childhood Cardiomyopathy Study, Longitudinal Studies, 030212 general & internal medicine, Child, education.field_of_study, Hazard ratio, Age Factors, Hypertrophic cardiomyopathy, Progression-Free Survival, Defibrillators, Implantable, 1117 Public Health And Health Services, Child, Preschool, Disease Progression, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Adrenergic beta-Antagonists, Population, Electric Countershock, 1102 Cardiovascular Medicine And Haematology, 03 medical and health sciences, Physiology (medical), Internal medicine, medicine, Humans, education, Retrospective Studies, business.industry, Myocardial cardiomyopathy disease, Australia, Infant, Newborn, Infant, 1103 Clinical Sciences, Retrospective cohort study, Cardiomyopathy, Hypertrophic, medicine.disease, Transplantation, Death, Sudden, Cardiac, Cardiovascular System & Hematology, Heart Transplantation, business
Abstract: Background: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. Methods: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0–10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. Results: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0–92.0) 1 year after presentation, 80% (95% CI, 69.0–87.0) at 10 years, and 78% (95% CI, 67.0–86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60–11.05; P =0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02–8.08; P =0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22–1.73; P z score (hazard ratio, 0.84; 95% CI, 0.74–0.95; P =0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with β-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. Conclusions: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.
Published: 2018

39. Identifying low-grade cellular rejection after heart transplantation in children by using gene expression profiling

Author: Yifang Hu, Melissa G.Y. Lee, Annie Xin, Slavica Praporski, Paul Monagle, Gordon K. Smyth, Robert G. Weintraub, Igor E. Konstantinov, Vera Ignjatovic, Axel Kallies, Anne Shipp, and William Y. Shi
Subjects: Graft Rejection, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Adolescent, Physiology, medicine.medical_treatment, 030204 cardiovascular system & hematology, Biology, Endomyocardial biopsy, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Child, Heart transplantation, Regulation of gene expression, Graft rejection, Gene Expression Profiling, Infant, Gold standard (test), Gene expression profiling, 030104 developmental biology, Gene Expression Regulation, Child, Preschool, Heart Transplantation, Female
Abstract: Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection after heart transplantation but is costly and invasive. This study aims to distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart transplantation in children by using global gene expression profiling in blood. A total of 106 blood samples with corresponding EMB from 18 children who underwent heart transplantation from 2011 to 2014 were analyzed (18 baseline/pretransplantation samples, 88 EMB samples). Corresponding rejection grades for each blood sample were 0R in 39% (34/88), 1R in 51% (45/88), and 2R in 10% (9/88). mRNA from each sample was sequenced. Differential expression analysis was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied to the most differentially expressed (DE) genes to identify rejection after transplantation. Mean age at transplantation was 10.0 ± 5.4 yr. Expression of B cell and T cell receptor sequences was used to measure the effect of posttransplantation immunosuppression. Follow-up samples had lower levels of immunoglobulin gene families compared with pretransplantation ( P < 3E-5) (lower numbers of activated B cells). T cell receptor alpha and beta gene families had decreased expression in 0R samples compared with pretransplantation ( P < 4E-5) but recovered to near baseline levels in 1R/2R samples. kNN using the most DE gene (MKS1) and k = 9 nearest neighbors correctly identified 83% (73/88) of 1R/2R compared with 0R by leave-one-out cross validation. Using a genomic approach we can distinguish low-grade cellular allograft rejection (1R/2R) from no rejection (0R) after heart transplantation in children despite a wide age range.
Published: 2018

40. Position Statement on the Diagnosis and Management of Familial Dilated Cardiomyopathy

Author: Renee Johnson, Julie McGaughran, Diane Fatkin, John Atherton, and Robert G. Weintraub
Subjects: Adult, Cardiomyopathy, Dilated, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Position statement, medicine.medical_specialty, business.industry, DNA Mutational Analysis, Familial dilated cardiomyopathy, Disease Management, 030204 cardiovascular system & hematology, 03 medical and health sciences, Early Diagnosis, 030104 developmental biology, 0302 clinical medicine, Internal medicine, Mutation, medicine, Cardiology, Humans, Female, Genetic Testing, Cardiology and Cardiovascular Medicine, business
Published: 2017

41. Dilated cardiomyopathy

Author: Robert G, Weintraub, Christopher, Semsarian, and Peter, Macdonald
Subjects: Cardiomyopathy, Dilated, 0303 health sciences, Adrenergic beta-Antagonists, Angiotensin-Converting Enzyme Inhibitors, General Medicine, 030204 cardiovascular system & hematology, Electrocardiography, 03 medical and health sciences, Extracorporeal Membrane Oxygenation, 0302 clinical medicine, Echocardiography, Risk Factors, Heart Transplantation, Humans, Genetic Predisposition to Disease, Genetic Testing, 030304 developmental biology
Abstract: Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction. Genetic mutations involving genes that encode cytoskeletal, sarcomere, and nuclear envelope proteins, among others, account for up to 35% of cases. Acquired causes include myocarditis and exposure to alcohol, drugs and toxins, and metabolic and endocrine disturbances. The most common presenting symptoms relate to congestive heart failure, but can also include circulatory collapse, arrhythmias, and thromboembolic events. Secondary neurohormonal changes contribute to reverse remodelling and ongoing myocyte damage. The prognosis is worst for individuals with the lowest ejection fractions or severe diastolic dysfunction. Treatment of chronic heart failure comprises medications that improve survival and reduce hospital admission-namely, angiotensin converting enzyme inhibitors and β blockers. Other interventions include enrolment in a multidisciplinary heart failure service, and device therapy for arrhythmia management and sudden death prevention. Patients who are refractory to medical therapy might benefit from mechanical circulatory support and heart transplantation. Treatment of preclinical disease and the potential role of stem-cell therapy are being investigated.
Published: 2017

42. Outcomes of the Arterial Switch Operation in Children Less Than 2.5 Kilograms

Author: Robert G. Weintraub, Yves d'Udekem, Igor E. Konstantinov, Anne Eva Bulstra, Benjamin R. Loyer, Christian P. Brizard, and Tyson A. Fricke
Subjects: Reoperation, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Treatment outcome, Hospital mortality, 030204 cardiovascular system & hematology, Body weight, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Hospital Mortality, Single institution, Kilogram, business.industry, Infant, Newborn, Infant, Mean age, Infant, Low Birth Weight, Surgery, Arterial Switch Operation, Low birth weight, Treatment Outcome, 030228 respiratory system, Great arteries, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Abstract: Children with body weight less than 2.5 kg who undergo the arterial switch operation (ASO) represent a challenging group. We sought to determine outcomes of patients with weight less than 2.5 kg at ASO at a single institution.All patients who underwent an ASO with biventricular repair and weighed less than 2.5 kg at time of surgery were identified from the hospital database and reviewed retrospectively.From 1983 to 2014, 870 patients underwent an ASO with biventricular repair at our institution. At the time of ASO, 31 patients (3.6%, 31 of 870) weighed less than 2.5 kg (mean 2.1; median 2.1; range, 1.1 to 2.4). Twenty-nine patients underwent an ASO for d-transposition of the great arteries, and 2 patients had an ASO for Taussig-Bing anomaly. Mean age at operation was 16 days (median 11; range, 3 to 66). There were 6 hospital deaths (19%, 6 of 31) among patients weighing less than 2.5 kg compared with a hospital mortality of 1.9% (16 of 839) among patients weighing more than 2.5 kg (p 0.0001). Mortality for children weighing 2.0 kg or less was 50% (5 of 10) compared with a mortality of 2.8% (1 of 21) for children weighing more than 2.0 kg but less than 2.5 kg. Four patients (13%, 4 of 31) required reoperation during hospital admission. Follow-up was available for 24 survivors (96%, 24 of 25). Mean follow-up was 13.2 years (median 11.9; range, 6 months to 25 years). There were no late deaths. Two patients (8%, 2 of 24) required late reoperation. No patient had more than mild neoaortic valve regurgitation, and all survivors were in New York Heart Association class I at last follow-up.Early mortality for children weighing less than 2.5 kg undergoing the ASO remains high; however, most of the mortality occurred in children weighing 2.0 kg or less. Long-term outcomes for survivors are excellent.
Published: 2017

43. Long-term outcomes of single-ventricle palliation for unbalanced atrioventricular septal defects: Fontan survivors do better than previously thought

Author: Edward Buratto, Yves d'Udekem, Igor E. Konstantinov, Xin Tao Ye, Christian P. Brizard, William Y. Shi, Gregory King, and Robert G. Weintraub
Subjects: Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Palliative care, Adolescent, Heart Ventricles, medicine.medical_treatment, 030204 cardiovascular system & hematology, Fontan Procedure, Risk Assessment, Hypoplastic left heart syndrome, Fontan procedure, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Abnormalities, Multiple, Child, Survival rate, Retrospective Studies, Heart septal defect, business.industry, Heart Septal Defects, Palliative Care, Hazard ratio, Australia, Infant, Retrospective cohort study, medicine.disease, Surgery, Survival Rate, Transplantation, Treatment Outcome, 030228 respiratory system, Echocardiography, Child, Preschool, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, Forecasting
Abstract: Single-ventricle palliation (SVP) for children with unbalanced atrioventricular septal defect (uAVSD) is thought to carry a poor prognosis, but limited data have been reported.We performed a retrospective review of children with uAVSD who underwent SVP at a single institution. Data were obtained from medical records and correspondence with general practitioners and cardiologists.Between 1976 and 2016, a total of 139 patients underwent SVP for uAVSD. A neonatal palliative procedure was performed in 83.5% of these patients (116 of 139), and early mortality occurred in 11.2% (13 of 116). Ninety-four patients underwent stage II palliation, with an early mortality of 6.4% (6 of 94). Eighty patients (57.6%) underwent Fontan completion, with an early mortality of 3.8% (3 of 80). Interstage mortality was 11.7% (12 of 103) between stages I and II and 17.0% (15 of 88) between stage II and Fontan. Long-term survival was 66.5% (95% confidence interval [CI], 57.9%-73.9%) at 5 years, 64.4% (95% CI, 55.5%-72.0%) at 15 years, and 57.8% (95% CI, 47.5%-66.8%) at 25 years. Survival post-Fontan was 94.9% (95% CI, 86.9%-98.0%) at 5 years, 92.0% (95% CI, 80.6%-96.8%) at 15 years, and 82.4% (95% CI, 61.5%-92.6%) at 25 years. Risk factors associated with death or transplantation were aortic atresia (hazard ratio [HR], 5.3; P = .03) and hypoplastic aortic arch (HR, 2.5; P = .02). Atrioventricular valve operations were required in 31.7% of the patients (44 of 139), with 31.8% of them (14 of 44) requiring a further operation.Children undergoing SVP for uAVSD have substantial mortality, with60% survival at 25 years. However, survival of children who achieve Fontan completion is better than has been reported previously.
Published: 2017

44. Outcomes of Subaortic Obstruction Resection in Children

Author: Phillip S. Naimo, Robert G. Weintraub, Malcolm Richardson, Christian P. Brizard, Andrew Bullock, Yves d'Udekem, Igor E. Konstantinov, and Julia S. Donald
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Aortic valve, medicine.medical_specialty, Time Factors, Heart disease, Aortic Valve Insufficiency, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Aortic valve repair, Internal medicine, Discrete Subaortic Stenosis, Humans, Medicine, Ventricular outflow tract, Cardiac Surgical Procedures, Child, Retrospective Studies, business.industry, Age Factors, Stroke Volume, Retrospective cohort study, Stroke volume, medicine.disease, Surgery, medicine.anatomical_structure, 030228 respiratory system, Child, Preschool, Cardiology, Female, Subvalvular Aortic Stenosis, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract: Studies of long-term outcomes of discrete subaortic stenosis are rare. Therefore, we reviewed the long-term outcomes of fibromuscular resection in children with subaortic stenosis over 26 years from a single institution.We conducted a retrospective review of all children (n=72) who underwent resection of subaortic obstruction for discrete subaortic stenosis between 1989 and 2015.Median age at surgery was 5.0 years (2.7-7.6 years). There were no operative deaths but three late deaths (4.2%, 3/72). Overall Kaplan-Meier survival at 10 years was 93.0 ± 3.9% (95% CI: 79.6, 97.7). Peak instantaneous left ventricular outflow tract Doppler gradient decreased from 74.2±36.7mmHg (16.0-242.0mmHg) preoperatively to 12.8±7.4mmHg (2.6-36.0mmHg) postoperatively (p0.001). Mean left ventricular outflow tract Doppler gradient decreased from 42.4±17.2mmHg (12.0-98.0) preoperatively to 7.5±2.7mmHg (1.4-19.3mmHg) postoperatively (p0.001). However, over the mean follow-up period of 7.8±6.1 years (0.1-25.2 years), 29.0% (20/69) of patients had recurrence and 18.8% (13/69) required reoperation at median time of 4.8 years (3.1-9.1 years) after the initial repair. Freedom from reoperation at 10 years was 71.1±7.1% (95% CI: 54.6, 82.3). Risk factors for reoperation were age less than five years at initial repair (p=0.036) and extension of the membrane to the aortic valve (p=0.001). Aortic insufficiency was present in 54.2% (39/72) of patients preoperatively. Progression of aortic insufficiency occurred in 38.9% (28/72). Involvement of the aortic valve at initial repair was associated with need for subsequent aortic valve repair or replacement (p=0.01).Resection of subaortic obstruction is associated with low mortality and morbidity. Recurrence and reoperation rates are high and progression of aortic insufficiency following subaortic resection is common. Therefore, these patients warrant close follow-up into adult life.
Published: 2017

45. Twenty-Five Year Outcomes of the Lateral Tunnel Fontan Procedure

Author: Robert G. Weintraub, Leeanne Grigg, Andrew Bullock, William Y. Shi, Robert N. Justo, Dorothy J. Radford, David S. Winlaw, Ajay J. Iyengar, Gavin R. Wheaton, Tom Wilson, Yves d'Udekem, Thomas L. Gentles, and Rachael Cordina
Subjects: Male, Time Factors, medicine.medical_treatment, 030204 cardiovascular system & hematology, Fontan Procedure, Postoperative Complications, 0302 clinical medicine, Risk Factors, Hospital Mortality, Registries, Treatment Failure, 030212 general & internal medicine, Child, Heart transplantation, education.field_of_study, Hazard ratio, General Medicine, surgical procedures, operative, Child, Preschool, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, Heart Defects, Congenital, Reoperation, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Heart Ventricles, Population, Disease-Free Survival, Fontan procedure, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, education, Survival rate, Retrospective Studies, business.industry, Australia, Retrospective cohort study, medicine.disease, Confidence interval, Surgery, Heart Transplantation, Supraventricular tachycardia, business, New Zealand
Abstract: The objective of this study was to characterize late outcomes of the lateral tunnel (LT) Fontan procedure. The outcomes of all patients who underwent an LT Fontan procedure in Australia and in New Zealand were analyzed. Original files were reviewed and outcomes data were obtained through a binational registry. Between 1980 and 2014, a total of 301 patients underwent an LT Fontan procedure across 6 major centers. There were 13 hospital mortalities, 21 late deaths, 8 Fontan conversions and revisions, 8 Fontan takedowns, and 4 heart transplantations. Overall survival at 15 and 25 years was 90% (95% confidence interval [CI]: 86%-93%) and 80% (95% CI: 69%-91%), respectively. Protein-losing enteropathy or plastic bronchitis was observed in 14 patients (5%). Freedom from late failure at 15 and 25 years was 88% (95% CI: 84%-92%) and 82% (95% CI: 76%-87%), respectively. Independent predictors of late Fontan failure were prolonged pleural effusions post Fontan operations (hazard ratio [HR] 3.06, 1.05-8.95, P = 0.041), age7 years at Fontan (vs 3-5 years, HR 9.7, 2.46-38.21, P = 0.001) and development of supraventricular tachycardia (HR 4.67, 2.07-10.58, P 0.001). Freedom from tachy- or bradyarrhythmias at 10 and 20 years was 87% (95% CI: 83%-91%) and 72% (95% CI: 66%-79%), respectively. Thromboembolic events occurred in 45 patients (16%, 26 strokes), and freedom from symptomatic thromboembolism at 10 and 20 years was 93% (95% CI: 89%-96%) and 80% (95% CI: 74%-86%), respectively. Over a 25-year period, the LT technique has achieved excellent late survival. As this population ages, it is at an increasing risk of failure and adverse events. We are likely to see an increasing proportion requiring heart transplantation and late reintervention.
Published: 2017

46. Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Author: Mohsen Bayati, Arvin Haj-Mirzaian, Mehran Asadi-Aliabadi, Maziar Moradi-Lakeh, Nasir Salam, Mohamad-Hani Temsah, Fatemeh Heydarpour, Davide Rasella, Kavumpurathu Raman Thankappan, Ghulam Mustafa, Sergey Konstantinovitch Vladimirov, Fereshteh Ansari, Dina Nur Anggraini Ningrum, Leonardo Roever, Oghenowede Eyawo, Koustuv Dalal, Ana-Laura Manda, Ritesh G. Menezes, Molly K. Miller-Petrie, Javad Yoosefi Lebni, Gebreamlak Gebremedhn Gebremeskel, Aziz Eftekhari, Oleguer Plana-Ripoll, Jon Wakefield, Sanjay Zodpey, Birhanu Geta, Amaha Kahsay, Edris Hasanpoor, Brijesh Sathian, Kala M. Mehta, Moritz U. G. Kraemer, Saeed Amini, Hesham M. Al-Mekhlafi, Abbas Yadegar, João Pedro Silva, Desmond Kuupiel, Anvar Asadi, Hamid Sharifi, Ebrahim Babaee, Dessalegn Ajema Berbada, Taddese Alemu Zerfu, Ian Davis, Mostafa Qorbani, Fatemeh Rajati, Samer Hamidi, Parvaiz A Koul, Foad Abd-Allah, Mojisola Oluwasanu, Syed Mohamed Aljunid, Elias Merdassa Roro, Mihaela Hostiuc, Robert S. Bernstein, Vahid Yazdi-Feyzabadi, Gebre Teklemariam Demoz, Irina Filip, Mu'awiyyah Babale Sufiyan, Amir Khater, Lidia Morawska, Sangram Kishor Patel, Robert C. Reiner, Joshua O. Akinyemi, Telma Zahirian Moghadam, Ali Akbar Fazaeli, Reza Malekzadeh, Olatunde Aremu, Mohammad Reza Salahshoor, Irfan Ullah, Gabrielle B. Britton, Gelin Xu, Nathaniel J Henry, Thomas R. Hird, Ronny Westerman, Vera Marisa Costa, Reza Assadi, Tiffany K. Gill, Chhabi Lal Ranabhat, Meysam Olfatifar, Sezer Kisa, Grant Rodgers Kemp, Mahmoud Yousefifard, Aleksandra Barac, Simon I. Hay, Walter Mendoza, Mohammad Zamani, Nader Jafari Balalami, Mahdi Safdarian, Manfred S. Green, Mahesh P A, Nahid Neamati, Pallab K. Maulik, Ali H. Mokdad, Joshua Longbottom, Somayeh Bohlouli, Ahmad Daryani, Ibrahim Abdollahpour, Mostafa Hosseini, Deborah Carvalho Malta, Nick Golding, Sheikh Mohammed Shariful Islam, Shirin Nosratnejad, Haidong Wang, Shadi Rahimzadeh, Pushpendra Kumar, Mehdi Noroozi, Andre M. N. Renzaho, Brent Bell, Huong Lan Thi Nguyen, Khaled Khatab, Meghdad Pirsaheb, Yousef Veisani, Katie R Nielsen, Ionut Negoi, Seyyed Meysam Mousavi, Amir Ashraf-Ganjouei, Mohammad Hassan Emamian, Joseph L Ward, Sharath Burugina Nagaraja, Songhomitra Panda-Jonas, Ettore Beghi, Azeem Majeed, Ivy Shiue, Delia Hendrie, Roghiyeh Faridnia, Seyed Mostafa Mir, Moslem Soofi, Ghobad Moradi, Mahsa Ghajarzadeh, Chandrashekhar T Sreeramareddy, Milad Hasankhani, Mohamed I Hegazy, Mika Shigematsu, Bryan L. Sykes, Vahid Alipour, Ruth W Kimokoti, Afshin Maleki, Nafiseh Baheiraei, Noore Alam, Jalal Arabloo, Mariam Molokhia, Kimberly B. Johnson, Amber Sligar, Nicole Davis Weaver, Kerem Shuval, Malede Mequanent Sisay, Paul H. Lee, Reza Ghadimi, Mahbobeh Faramarzi, Natalia V. Bhattacharjee, Ehsan Sadeghi, Brandon V. Pickering, Animika Pandey, Ana Isabel Ribeiro, Felix Greaves, Sameer Vali Gopalani, Joel M. Francis, Alyssa N. Sbarra, Yun Jin Kim, Agus Sudaryanto, Hebat Allah Salah A. Yousof, Hadi Pourjafar, Tomohide Yamada, Alireza Rafiei, Rosario Cárdenas, Mohammad Khazaei, Hasan Yusefzadeh, Rahman Shiri, Girmay Teklay Weldesamuel, Zahra Jorjoran Shushtari, Michael Collison, Stanislav S. Otstavnov, Narayanaswamy Venketasubramanian, Yahya Salimi, Naohiro Yonemoto, Ahmad Ghashghaee, Soewarta Kosen, Al Artaman, Surendra Karki, Tariq Jamal Siddiqi, Lorenzo Monasta, Amit Arora, Christopher S Yilgwan, Ahamarshan Jayaraman Nagarajan, Adnan Kisa, Gholamreza Roshandel, Vahid Rashedi, Daniel Diaz, Amir Vahedian-Azimi, Erkin M. Mirrakhimov, Nuworza Kugbey, Zohreh Arefi, Benjamin B. Massenburg, Robert G. Weintraub, Lauren E. Schaeffer, Alexandre C. Pereira, Mehdi Hosseinzadeh, Milena M Santric Milicevic, Ai Koyanagi, Mehran Shams-Beyranvand, Salman Khazaei, Olalekan A. Uthman, Mohamed Hsairi, Nuno Taveira, Masoud Foroutan, Jayendra Sharma, Hanna Demelash Desyibelew, Max Roser, Keivan Ahmadi, Yousef Khader, Hamideh Salimzadeh, Ali Bijani, Shanshan Li, Mehran Alijanzadeh, Florian Fischer, Aziz Sheikh, Eun-Kee Park, Stefan Listl, Smita Pakhale, Brian J. Hall, Alireza Zangeneh, Ravi Mehrotra, Kidu Gidey Weldegwergs, Mahdi Afshari, Son Hoang Nguyen, Francisco Rogerlândio Martins-Melo, Rupak Desai, Aziz Rezapour, Hassan Magdy Abd El Razek, Gillian I. Hollerich, Reza Saeedi, Iman El Sayed, Olayinka Stephen Ilesanmi, Ben Lacey, Soheil Ebrahimpour, Laura Dwyer-Lindgren, Roya Ebrahimi, Bolajoko O. Olusanya, Tommi Vasankari, Siamak Sabour, Theo Vos, Tuomo J. Meretoja, Job F M van Boven, Nataliya Foigt, Mojtaba Hoseini-Ghahfarokhi, Saleh Salehi Zahabi, Mehdi Fazlzadeh, Neeraj Bedi, Hamed Mirjalali, Payman Salamati, P N Sylaja, Ted R. Miller, George J. Milne, Alaa Badawi, Muhammad Usman, Amir Hasanzadeh, Michelle L. Bell, Giang Thu Vu, Masoud Behzadifar, Manasi Kumar, Mona M. Khater, Josip Car, Nafis Sadat, Mostafa Leili, Mehdi Sharif, Hadi Hassankhani, Mowafa Househ, Joshua A. Salomon, Morteza Mansourian, G Anil Kumar, João C. Fernandes, Tufa Kolola, Arya Haj-Mirzaian, Masood Ali Shaikh, Keyghobad Ghadiri, Andrew T Olagunju, Bahram Armoon, Beatriz Paulina Ayala Quintanilla, Samantha Perkins, Mohsen Mazidi, Stefan Lorkowski, Sagnik Dey, Edward J Mills, Ali Kabir, Maryam Khazaei-Pool, Mohammad Rabiee, Arianna Maever L. Amit, John S. Ji, Sivan Yegnanarayana Iyer Saraswathy, Fares Alahdab, Vafa Rahimi-Movaghar, Martin McKee, Hadi Parsian, Ejaz Ahmad Khan, Amirhossein Sahebkar, Paramjit Gill, Dara K. Mohammad, Naznin Hossain, Karen M. Tabb, Annie J. Browne, Abdallah M. Samy, Elham Ehsani-Chimeh, Nelson G.M. Gomes, Destallem Gebremedhin Gebre, Fakher Rahim, Sheetal D. Lad, Rajat Das Gupta, Yash Jobanputra, Rajesh Sharma, Davoud Adham, Richard Ofori-Asenso, Farah Daoud, Aso Mohammad Darwesh, Meghnath Dhimal, Pranab Chatterjee, Javad Javidnia, Shafiu Mohammed, Amir Abdoli, Josep Maria Haro, Stefanie Watson, Behnam Nabavizadeh, Masoumeh Abbasi, Kefyalew Addis Alene, Marzieh Nojomi, G. K. Mini, Abbas Mosapour, Cyrus Cooper, Yirga Legesse Nirayo, Jagdish Khubchandani, Muhammed Magdy Abd El Razek, Faramarz Shaahmadi, Satar Rezaei, Mahdi Sharif-Alhoseini, Francesco Saverio Violante, Eyal Oren, Erfan Zabeh, Atte Meretoja, Nicholas Graetz, Kris J. Krohn, Anthony Masaka, Oladimeji Adebayo, Mikk Jürisson, Faris Lami, Marcos Roberto Tovani-Palone, Chloe Shields, Yahya Safari, Yasir Waheed, Dilaram Acharya, Seyed Mohammad Riahi, Jan-Walter De Neve, Carlos A Castañeda-Orjuela, Alberto Ortiz, Samad Azari, Shymaa Enany, Maha Ezalarab, Salvatore Rubino, Enayatollah Homaie Rad, Roghayeh Khabiri, Seyed-Mohammad Fereshtehnejad, Yuming Guo, Sonia Saxena, Nicholas J K Breitborde, Takeshi Fukumoto, Hamid Yimam Hassen, Thomas Pilgrim, Yasser Vasseghian, Dragos Virgil Davitoiu, Farid Najafi, Sathish Thirunavukkarasu, Ali Rostami, Efat Mohamadi, Sameh Magdeldin, Hedley Quintana, Cyrus Alinia, Rodrigo Sarmiento-Suarez, Roya Safari-Faramani, Leila Doshmangir, Kewal Krishan, Karen Sliwa, Nazrul Islam, Neal Marquez, Genet Melak Alamene, Andem Effiong, Khanh Bao Tran, Amir Kasaeian, Adeladza Kofi Amegah, Hamidreza Haririan, Maha El Tantawi, Anders Larsson, André Faro, Rushdia Ahmed, Amir Shamshirian, Josephine W. Ngunjiri, Yousef Moradi, Sharareh Eskandarieh, Evanson Z. Sambala, Nelson Alvis-Guzman, Mehdi Moradinazar, Lauren Woyczynski, Parul Puri, Yunquan Zhang, Navid Manafi, Vinay Nangia, Joan B. Soriano, Victor Adekanmbi, Sofia Androudi, Carl Abelardo T. Antonio, Morteza Abdullatif Khafaie, Netsanet Fentahun, Achala Upendra Jayatilleke, David L. Smith, Solomon Sisay, Giuseppe Gorini, Meysam Behzadifar, Charles Shey Wiysonge, Bach Xuan Tran, Lal B. Rawal, Arefeh Babazadeh, Damaris K. Kinyoki, Morteza Shamsizadeh, Ziad El-Khatib, Zohreh Anbari, Abdol Sattar Pagheh, Ranjani Somayaji, Frank B. Osei, Nancy Fullman, Zahid A Butt, Ai-Min Wu, Tahereh Pashaei, Benn Sartorius, Aaron Osgood-Zimmerman, Sachin R Atre, Mehdi Ahmadi, Chalachew Genet Akal, Aubrey J. Levine, Mohammad Fareed, Quique Bassat, Khalid A Altirkawi, Ensiyeh Jenabi, Daem Roshani, Mina Anjomshoa, Jasvinder A. Singh, Yafeng Wang, Samath D Dharmaratne, Enrico Rubagotti, Ruxandra Irina Negoi, Reinhard Busse, Abdullah Al Mamun, Yoshan Moodley, Mohammed Almalki, Peter W. Gething, Alireza Khatony, Usman Iqbal, Soraya Nouraei Motlagh, Roy Burstein, Hamed Zandian, Rakhi Dandona, Mojtaba Bagherzadeh, Majid Pirestani, Jaifred Christian F. Lopez, Chuanhua Yu, Arash Ziapour, Seyed Sina Naghibi Irvani, Bárbara Niegia Garcia Goulart, Pascual R. Valdez, Amir Jalali, Chukwudi A Nnaji, Kelechi Elizabeth Oladimeji, Tomislav Mestrovic, Isidora S. Vujcic, Osayomwanbo Osarenotor, Azin Nahvijou, Chi Linh Hoang, Christopher J L Murray, Mustafa Z. Younis, Veincent Christian Filipino Pepito, Andre Rodrigues Duraes, Yuan-Pang Wang, Felix Akpojene Ogbo, Aniruddha Deshpande, Nicholas J Kassebaum, Jacek Jerzy Jozwiak, Soghra Bagheri, Paul S. F. Yip, Sree Bhushan Raju, Sadaf G. Sepanlou, Kebede Deribe, Junaid Khan, Mohammad Aghaali, Lalit Dandona, Masoud Moradi, Molly R Nixon, Bruno Piassi Sao Jose, Atalay Goshu Muluneh, Mohammad Hasan Imani-Nasab, Naser Mohammad Gholi Mezerji, Abdullah Sulieman Terkawi, Sojib Bin Zaman, Muhammad Shahzeb Khan, Maysaa El Sayed Zaki, Gebrekiros Gebremichael Meles, Suraj Bhattarai, Yared Belete Belay, Ammas Siraj Mohammed, Dawit Zewdu Wondafrash, Abbas Balouchi, Silvano Gallus, Mohammad Abdollahi, Long Hoang Nguyen, Zulfiqar A Bhutta, Jean Jacques Noubiap, Mehdi Naderi, Bernhard T. Baune, Lucas Earl, Doris D. V. Ortega-Altamirano, Michael R.M. Abrigo, Farkhonde Salehi, Hamed Kalani, Mayowa O. Owolabi, Feleke Mekonnen Demeke, Lee Ling Lim, Ulrich O Mueller, Laurie B. Marczak, Peter Njenga Keiyoro, Ehsan Ahmadpour, Navid Rabiee, Dinh-Toi Chu, Vasily Vlassov, Bradford D Gessner, Tsegaye Tewelde Gebrehiwot, Sorin Hostiuc, Bakhtiar Piroozi, Mahdieh Abbasalizad-Farhangi, Takahiro Tabuchi, Philimon Gona, Bahar Ataeinia, Azra Ramezankhani, Duduzile Ndwandwe, Obinna Onwujekwe, Zohreh Rahimi, Seyedmojtaba Seyedmousavi, Wagaye Fentahun Chanie, Neda Kianipour, Rizwan Suliankatchi Abdulkader, Dhirendra N Sinha, Young-Ho Khang, Paula Moraga, Manoochehr Karami, Solomon Olum, Rafael Tabarés-Seisdedos, Zemenu Tadesse Tessema, Amir Radfar, Kiomars Sharafi, Rohollah Kalhor, Benjamin K. Mayala, Mahmood Moosazadeh, David C. Schwebel, Jost B. Jonas, Quyen G. To, Ester Cerin, Martin Amogre Ayanore, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Research Institute for Asthma and COPD (GRIAC), Veritati - Repositório Institucional da Universidade Católica Portuguesa, Department of Earth Observation Science, Faculty of Geo-Information Science and Earth Observation, UT-I-ITC-ACQUAL, GeoHealth, HUS Neurocenter, Department of Neurosciences, Neurologian yksikkö, Clinicum, HUS Comprehensive Cancer Center, Staff Services, Department of Surgery, University of Helsinki, Islam, Nazrul [0000-0003-3982-4325], Apollo - University of Cambridge Repository, Burstein R., Henry N.J., Collison M.L., Marczak L.B., Sligar A., Watson S., Marquez N., Abbasalizad-Farhangi M., Abbasi M., Abd-Allah F., Abdoli A., Abdollahi M., Abdollahpour I., Abdulkader R.S., Abrigo M.R.M., Acharya D., Adebayo O.M., Adekanmbi V., Adham D., Afshari M., Aghaali M., Ahmadi K., Ahmadi M., Ahmadpour E., Ahmed R., Akal C.G., Akinyemi J.O., Alahdab F., Alam N., Alamene G.M., Alene K.A., Alijanzadeh M., Alinia C., Alipour V., Aljunid S.M., Almalki M.J., Al-Mekhlafi H.M., Altirkawi K., Alvis-Guzman N., Amegah A.K., Amini S., Amit A.M.L., Anbari Z., Androudi S., Anjomshoa M., Ansari F., Antonio C.A.T., Arabloo J., Arefi Z., Aremu O., Armoon B., Arora A., Artaman A., Asadi A., Asadi-Aliabadi M., Ashraf-Ganjouei A., Assadi R., Ataeinia B., Atre S.R., Quintanilla B.P.A., Ayanore M.A., Azari S., Babaee E., Babazadeh A., Badawi A., Bagheri S., Bagherzadeh M., Baheiraei N., Balouchi A., Barac A., Bassat Q., Baune B.T., Bayati M., Bedi N., Beghi E., Behzadifar M., Belay Y.B., Bell B., Bell M.L., Berbada D.A., Bernstein R.S., Bhattacharjee N.V., Bhattarai S., Bhutta Z.A., Bijani A., Bohlouli S., Breitborde N.J.K., Britton G., Browne A.J., Nagaraja S.B., Busse R., Butt Z.A., Car J., Cardenas R., Castaneda-Orjuela C.A., Cerin E., Chanie W.F., Chatterjee P., Chu D.-T., Cooper C., Costa V.M., Dalal K., Dandona L., Dandona R., Daoud F., Daryani A., Das Gupta R., Davis I., Davis Weaver N., Davitoiu D.V., De Neve J.-W., Demeke F.M., Demoz G.T., Deribe K., Desai R., Deshpande A., Desyibelew H.D., Dey S., Dharmaratne S.D., Dhimal M., Diaz D., Doshmangir L., Duraes A.R., Dwyer-Lindgren L., Earl L., Ebrahimi R., Ebrahimpour S., Effiong A., Eftekhari A., Ehsani-Chimeh E., El Sayed I., El Sayed Zaki M., El Tantawi M., El-Khatib Z., Emamian M.H., Enany S., Eskandarieh S., Eyawo O., Ezalarab M., Faramarzi M., Fareed M., Faridnia R., Faro A., Fazaeli A.A., Fazlzadeh M., Fentahun N., Fereshtehnejad S.-M., Fernandes J.C., Filip I., Fischer F., Foigt N.A., Foroutan M., Francis J.M., Fukumoto T., Fullman N., Gallus S., Gebre D.G., Gebrehiwot T.T., Gebremeskel G.G., Gessner B.D., Geta B., Gething P.W., Ghadimi R., Ghadiri K., Ghajarzadeh M., Ghashghaee A., Gill P.S., Gill T.K., Golding N., Gomes N.G.M., Gona P.N., Gopalani S.V., Gorini G., Goulart B.N.G., Graetz N., Greaves F., Green 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C.J.L., and Hay S.I.
Subjects: Survival, RJ101, Mortalidad Infantil, HB, UNDER-5 MORTALITY, Global Health, Pediatrics, 0302 clinical medicine, 3123 Gynaecology and paediatrics, Child death, Infant Mortality, Epidemiology, Global health, Middle income country, Nacimiento vivo, 030212 general & internal medicine, 10. No inequality, Child, POPULATION, Developing world, education.field_of_study, Public health, Multidisciplinary, Geography, Mortality rate, wa_900, 1. No poverty, SUCCESS, Pediatrik, A900 Others in Medicine and Dentistry, 3142 Public health care science, environmental and occupational health, 3. Good health, Child Mortality, Death children, VACCINATION, HEALTH, ws_100, INTERVENTIONS, AFRICA, medicine.medical_specialty, United Nations, General Science & Technology, 030231 tropical medicine, Population, Developing country, Article, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], ITC-HYBRID, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Social Justice, Recién nacido, Neonatal deaths, medicine, SYSTEMATIC ANALYSIS, Organizational Objectives, Humans, education, Developing Countries, business.industry, Infant, Newborn, Infant, CIVIL REGISTRATION, Paediatrics, Child survival, Newborn, PREVENTION, Infant mortality, wa_320, ws_200, Child mortality, Socioeconomic Factors, ITC-ISI-JOURNAL-ARTICLE, Human medicine, Paediatrics, Public health, Developing world, business, Demography
Abstract: Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations., A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.
Published: 2019

47. Late Breaking Abstract - Validation of the REVEAL 2.0 Risk Score with the Australian and New Zealand Pulmonary Hypertension Registry Cohort

Author: David S. Celermajer, Nathan Dwyer, Edmund M.T. Lau, Dominic Keating, Mark Horrigan, Geoff Strange, James Anderson, Nicholas Collins, Anne Keogh, Eugene Kotlyar, Tanya McWilliams, Robert G. Weintraub, K. Whyte, Bronwen Rhodes, Raymond L. Benza, John Feenstra, Vivek Thakkar, Jeremy P. Wrobel, Helen Whitford, P. Steele, Melanie Lavender, Trevor Williams, and Carolyn Corrigan
Subjects: Risk category, medicine.medical_specialty, Framingham Risk Score, business.industry, Internal medicine, Cohort, Separation (statistics), Medicine, business, medicine.disease, Risk assessment, Pulmonary hypertension, Prognostic models
Abstract: Background: Objective multi-parametric risk assessment is recommended in pulmonary arterial hypertension (PAH) to identify patients at risk of early morbidity and mortality. The REVEAL 2.0 Risk Score is a new model proposed for the follow-up of PAH patients but it has not been externally validated. Methods: The REVEAL 2.0 Risk Score was applied to a mixed prevalent and incident cohort of PAH patients (n=1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier (KM) survival was estimated for each REVEAL 2.0 Risk Score strata and for a broader three-category (low, intermediate, high-risk) model. Results: The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ registry cohort, with c-statistic 0.74 (both for full 8-tier and three-category models). When applied to incident cases only, c-statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12 and 60-months survival estimates (all risk categories comparisons p Conclusion: The REVEAL 2.0 risk score was validated in a large external cohort from the PHSANZ Registry. The REVEAL 2.0 model can be applied for risk assessment of PAH patients at follow-up. The simplified 3-category model may be preferred for clinical use and for future comparison with other prognostic models.
Published: 2019

48. Management of People With a Fontan Circulation: a Cardiac Society of Australia and New Zealand Position statement

Author: Paul Monagle, Winita Hardikar, Nadine A. Kasparian, Brian Le, Dominica Zentner, Juliet Ward, Kathryn Rice, Sebastian Greenway, Leeanne Grigg, Jenny Hynson, Clare O’Donnell, Gary F. Sholler, Siddharth Sood, David S. Celermajer, Michael Cheung, K. Marshall, Jonathan R. Skinner, Ajay J. Iyengar, Cameron Bridgman, Andrew M. Davis, Bernadette O'Connor, Robert G. Weintraub, William Wilson, Belinda Frank, Tim Hornung, Robert N. Justo, David S. Winlaw, Thomas L. Gentles, Julian Ayer, Gillian M. Blue, K. Eagleson, Karin du Plessis, Andreas Pflaumer, Kirsten Finucane, Evelyn Culnane, Yves d'Udekem, David C. McGiffin, Luke J. Burchill, Paul A. James, Angela Wood, Tom Wilson, Mark A. McGuire, Rachael Cordina, Jonathan M. Kalman, Julie Neilsen, Jacob Mathew, and Ben Moore
Subjects: Pulmonary and Respiratory Medicine, Position statement, Heart Defects, Congenital, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Heart disease, medicine.medical_treatment, Improved survival, 030204 cardiovascular system & hematology, Fontan circulation, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Multidisciplinary approach, Health care, medicine, Humans, 030212 general & internal medicine, Registries, Intensive care medicine, Societies, Medical, business.industry, Australia, medicine.disease, Ventricular assist device, Cardiology and Cardiovascular Medicine, business, New Zealand
Abstract: The Fontan circulation describes the circulatory state resulting from an operation in congenital heart disease where systemic venous return is directed to the lungs without an intervening active pumping chamber. As survival increases, so too does recognition of the potential health challenges. This document aims to allow clinicians, people with a Fontan circulation, and their families to benefit from consensus agreement about management of the person with a Fontan circulation. The document was crafted with input from a multidisciplinary group of health care providers as well as individuals with a Fontan circulation and families. It is hoped that the shared common vision of long-term wellbeing will continue to drive improvements in care and quality of life in this patient population and eventually translate into improved survival. KEYPOINTS.
Published: 2019

49. Retrospective Validation of the REVEAL 2.0 Risk Score With the Australian and New Zealand Pulmonary Hypertension Registry Cohort

Author: David S. Celermajer, Jeremy P. Wrobel, Fiona Kermeen, John Feenstra, P. Steele, Trevor Williams, Edmund M.T. Lau, Helen Whitford, Tanya McWilliams, K. Whyte, Melanie Lavender, Bronwen Rhodes, Anne Keogh, Carolyn Corrigan, Mark Horrigan, Nathan Dwyer, James Anderson, Nicholas Collins, Dominic Keating, Raymond L. Benza, Geoff Strange, Eugene Kotlyar, Robert G. Weintraub, and Vivek Thakkar
Subjects: Pulmonary and Respiratory Medicine, Male, medicine.medical_specialty, Hypertension, Pulmonary, Separation (statistics), Critical Care and Intensive Care Medicine, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Prevalence, Medicine, Humans, 030212 general & internal medicine, Registries, Disease management (health), Statistic, Prognostic models, Retrospective Studies, Framingham Risk Score, business.industry, Incidence, Australia, Disease Management, Middle Aged, medicine.disease, Prognosis, Pulmonary hypertension, Survival Analysis, 030228 respiratory system, Cohort, Female, Cardiology and Cardiovascular Medicine, Risk assessment, business, Algorithms, New Zealand
Abstract: Pulmonary arterial hypertension (PAH) prognosis has improved with targeted therapies; however, the long-term outlook remains poor. Objective multiparametric risk assessment is recommended to identify patients at risk of early morbidity and mortality, and for optimization of treatment. The US Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 risk score is a new model proposed for the follow-up of patients with PAH but has not been externally validated.The REVEAL 2.0 risk score was applied to a mixed prevalent and incident cohort of patients with PAH (n = 1,011) from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) Registry. Kaplan-Meier survival was estimated for each REVEAL 2.0 risk score strata and for a simplified three-category (low, intermediate, and high risk) model. Sensitivity analysis was performed on an incident-only cohort.The REVEAL 2.0 model effectively discriminated risk in the large external PHSANZ Registry cohort, with a C statistic of 0.74 (both for full eight-tier and three-category models). When applied to incident cases only, the C statistic was 0.73. The three-category REVEAL 2.0 model demonstrated robust separation of 12- and 60-month survival estimates (all risk category comparisons P .001). Although the full eight-tier REVEAL 2.0 model separated patients at low, intermediate, and high risk, survival estimates overlapped within some of the intermediate- and high-risk strata.The REVEAL 2.0 risk score was validated in a large external cohort from the PHSANZ Registry. The REVEAL 2.0 model can be applied for risk assessment of patients with PAH at follow-up. The simplified three-category model may be preferred for clinical use and for future comparison with other prognostic models.
Published: 2019

50. Long-term outcomes following repair of truncus arteriosus and interrupted aortic arch

Author: Tyson A. Fricke, Christian P. Brizard, Robert G. Weintraub, Melissa G.Y. Lee, Phillip S. Naimo, Yves d'Udekem, and Igor E. Konstantinov
Subjects: Pulmonary and Respiratory Medicine, Aortic arch, Reoperation, medicine.medical_specialty, Truncus Arteriosus, Aorta, Thoracic, 030204 cardiovascular system & hematology, Anastomosis, Truncus arteriosus, Aortic Coarctation, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, medicine, Humans, Aorta, business.industry, Interrupted aortic arch, Infant, Newborn, General Medicine, medicine.disease, Truncus Arteriosus, Persistent, Surgery, Treatment Outcome, 030228 respiratory system, Truncus, Descending aorta, cardiovascular system, Deep hypothermic circulatory arrest, Cardiology and Cardiovascular Medicine, business
Abstract: OBJECTIVES: We aim to evaluate the long-term outcomes following repair of truncus arteriosus with an interrupted aortic arch. METHODS: We reviewed all children (n = 24) who underwent repair of truncus arteriosus and an interrupted aortic arch between 1979 and 2018 in a single institution. The morphology of the interrupted aortic arch was type A in 5, type B in 18 and type C in 1. RESULTS: The median age at repair was 10 days and the median weight was 3.1 kg. Direct end-to-side anastomosis of the ascending and descending aorta was performed in 16 patients (67%, 16/24), patch augmentation in 5 patients (21%, 5/24) and direct anastomosis with the use of an interposition graft to the descending aorta in 2 patients (8%, 2/24). One patient, the first in the series, underwent interrupted aortic arch repair via subclavian flap aortoplasty prior to truncus repair. A period of deep hypothermic circulatory arrest was used in 16 patients, and isolated cerebral perfusion was used in 8 patients. The early mortality rate was 17% (4 out of 24 patients). There were no late deaths and overall survival was 83 ± 8% [95% confidence interval (CI) 61-93] at 20 years. Freedom from any reoperation was 33 ± 11% (95% CI 14-54) at 5 years and 13 ± 9% (95% CI 2-34) at 10 years. Six patients underwent 10 aortic reoperations. Freedom from aortic arch reoperation was 69 ± 11% (95% CI 42-85) at 10 and 20 years. Follow-up was 95% complete (19/20), with a median follow-up time of 20 years. At last follow-up, no clinically significant aortic arch obstruction was identified in any patient, and all patients were in New York Heart Association Class I/II. CONCLUSIONS: Repair of truncus arteriosus with an interrupted aortic arch with direct end-to-side anastomosis results in good survival beyond hospital discharge. Although the long-term functional state of patients is good, reoperation rates are high.
Published: 2019

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