Publications by authors named "Luc Mertens"

275 Publications

Multicentre prospective observational study exploring the predictive value of functional echocardiographic indices for early identification of preterm neonates at risk of developing chronic pulmonary hypertension secondary to chronic neonatal lung disease.

BMJ Open 2021 Mar 31;11(3):e044924. Epub 2021 Mar 31.

Paediatrics, Sinai Health System, Toronto, Ontario, Canada

Introduction: Although chronic pulmonary hypertension (cPH) secondary to chronic neonatal lung disease is associated with increased mortality and respiratory and neurodevelopmental morbidities, late diagnosis (typically ≥36 weeks postmenstrual age, PMA) and the use of qualitative echocardiographic diagnostic criterion (flat interventricular septum in systole) remain significant limitations in clinical care. Our objective in this study is to evaluate the utility of relevant quantitative echocardiographic indices to identify cPH in preterm neonates, early in postnatal course and to develop a diagnostic test based on the best combination of markers.

Methods And Analysis: In this ongoing international prospective multicentre observational diagnostic accuracy study, we aim to recruit 350 neonates born <27 weeks PMA and/or birth weight <1000 g and perform echocardiograms in the third week of age and at 32 weeks PMA (early diagnostic assessments, EDA) in addition to the standard diagnostic assessment (SDA) for cPH at 36 weeks PMA. Predefined echocardiographic markers under investigation will be measured at each EDA and examined to create a scoring system to identify neonates who subsequently meet the primary outcome of cPH/death at SDA. Diagnostic test characteristics will be defined for each EDA. Pulmonary artery acceleration time and tricuspid annular plane systolic excursion are the primary markers of interest.

Ethics And Dissemination: Ethics approval has been received by the Mount Sinai Hospital Research Ethics Board (REB) (#16-0111-E), Sunnybrook Health Sciences Centre REB (#228-2016), NHS Health Research Authority (IRAS 266498), University of Iowa Human Subjects Office/Institutional Review Board (201903736), Rotunda Hospital Research and Ethics Committee (REC-2019-008), and UBC Children's and Women's REB (H19-02738), and is under review at Boston Children's Hospital Institutional Review Board. Study results will be disseminated to participating families in lay format, presented to the scientific community at paediatric and critical care conferences and published in relevant peer-reviewed journals.

Trail Registration Number: NCT04402645.
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http://dx.doi.org/10.1136/bmjopen-2020-044924DOI Listing
March 2021

Comparison of Clinical and Social Characteristics of Canadian Youth Living With Type 1 and Type 2 Diabetes.

Can J Diabetes 2021 Jan 22. Epub 2021 Jan 22.

Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada; Department of Pediatrics and Child Health, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Can-SOLVE CKD SPOR Network, Canada. Electronic address:

Objectives: Our aim in this study was to describe the clinical and social characteristics of 2 Canadian cohorts of adolescents with diabetes.

Methods: Participants from the Improving renal Complications in Adolescents with type 2 diabetes through REsearch (iCARE) study (n=322) and the Early Determinants of Cardio-Renal Disease in Youth With Type 1 Diabetes (n=199) study were compared.

Results: Adolescents were 10 to 18 years of age (mean ± standard deviation: 14.8±2.4 years). The T2DM cohort had a shorter duration of diabetes. Both groups had glycated hemoglobin levels above target. The type 2 diabetes (T2D) cohort was comprised of predominantly Indigenous youth. The type 1 diabetes (T1D) cohort was 58.3% European/Caucasian, with a high proportion (41.7%) of visible minority groups (Afro-Caribbean, Asian/Pacific Islander, Hispanic). The prevalence of obesity, hypertension, left ventricular hypertrophy, albuminuria and hyperfiltration was higher in the T2D cohort. The T1D cohort was more socially and economically advantaged in all 4 dimensions of health inequality.

Conclusions: There are significant differences in clinical and social characteristics of adolescents with T2D and T1D in Canada. Both have inadequate glycemic control with evidence of onset and progression of diabetes-related complications.
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http://dx.doi.org/10.1016/j.jcjd.2021.01.008DOI Listing
January 2021

Right Ventricular Flow Dynamics in Dilated Right Ventricles: Energy Loss Estimation Based on Blood Speckle Tracking Echocardiography-A Pilot Study in Children.

Ultrasound Med Biol 2021 Jun 6;47(6):1514-1527. Epub 2021 Mar 6.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Children's Clinic, St. Olav's University Hospital, Trondheim, Norway.

Using blood speckle tracking (BST) based on high-frame-rate echocardiography (HFRE), we compared right ventricle (RV) flow dynamics in children with atrial septal defects (ASDs) and repaired tetralogy of Fallot (rTOF). Fifty-seven children with rTOF with severe pulmonary insufficiency (PI) (n = 21), large ASDs (n = 11) and healthy controls (CTL, n = 25) were included. Using a flow phantom, we studied the effects of imaging plane and smoothing parameters on 2-D energy loss (EL). RV diastolic EL was similar in ASD and rTOF, but both were greater than in CTL. Locations of high EL were similar in all groups in systole, occurring in the RV outflow tract and around the tricuspid valve leaflets in early diastole. An additional apical early diastolic area of EL was noted in rTOF, corresponding to colliding tricuspid inflow and PI. The flow phantom revealed that EL varied with imaging plane and smoothing settings but that the EL trend was preserved if kept consistent.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.02.004DOI Listing
June 2021

Longitudinal prediction of transplant-free survival by echocardiography in pediatric dilated cardiomyopathy.

Can J Cardiol 2020 Dec 18. Epub 2020 Dec 18.

The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: The prognostic significance of serial echocardiography and its rate of change in children with dilated cardiomyopathy (DCM) is incompletely defined.

Methods: We retrospectively analyzed up to 4 serial echocardiograms. Associations between mortality/transplant and echo parameters over time and between outcomes and the rate of change of echo parameters were analyzed; estimating patient-specific intercepts and slopes using linear regression models.

Results: Fifty-seven DCM children were studied (50% male; median-age 0.6 years; average follow-up 2.1±2.4 years). The median time to transplant or death was 2.0 years. Increased left ventricular (LV) diastolic (LVEDD) and systolic (LVESD) dimensions and myocardial performance index (MPI) were associated with increased mortality and transplant risk. Increased LV ejection fraction, mitral E-deceleration time, RV fractional area change, and tricuspid annular plane systolic excursion were associated with reduced mortality and transplant risk. Transplant/mortality likelihood increased by 41.6% and 19.8% for each unit increase in LVEDD and LVESD z-scores, respectively (LVEDD: HR [95% CI] = 1.416 [1.285, 1.560], p<0.001; LVESD: HR [95% CI]=1.198 [1.147, 1.251], p<0.001). A higher monthly change in LVESD z-score increased transplant/mortality likelihood by 85.6% (HR 1.856 [1.572, 2.191], p=0.015). Greater change in mitral E/e` (HR 0.707 [0.636, 0.786], p<0.001) and RV MPI (HR 0.412 [0.277, 0.613], p<0.001) were associated with reduced mortality and transplant risk.

Conclusions: LV and RV systolic and diastolic dimensions and function over time and their rate of change are associated with risk for transplant and mortality in childhood DCM. Serial changes in these parameters may be useful to predict clinical outcomes.
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http://dx.doi.org/10.1016/j.cjca.2020.12.010DOI Listing
December 2020

Imaging the adult with simple shunt lesions: position paper from the EACVI and the ESC WG on ACHD. Endorsed by AEPC (Association for European Paediatric and Congenital Cardiology).

Eur Heart J Cardiovasc Imaging 2020 Dec 18. Epub 2020 Dec 18.

Department of Adult Congenital Heart Disease, National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London, UK.

In 2018, the position paper 'Imaging the adult with congenital heart disease: a multimodality imaging approach' was published. The paper highlights, in the first part, the different imaging modalities applied in adult congenital heart disease patients. In the second part, these modalities are discussed more detailed for moderate to complex anatomical defects. Because of the length of the paper, simple lesions were not touched on. However, imaging modalities to use for simple shunt lesions are still poorly known. One is looking for structured recommendations on which they can rely when dealing with an (undiscovered) shunt lesion. This information is lacking for the initial diagnostic process, during repair and at follow-up. Therefore, this paper will focus on atrial septal defect, ventricular septal defect, and persistent arterial duct. Pre-, intra-, and post-procedural imaging techniques will be systematically discussed. This position paper will offer algorithms that might help at a glance. The document is prepared for general cardiologists, trainees, medical students, imagers/technicians to select the most appropriate imaging modality and to detect the requested information for each specific lesion. It might serve as reference to which researchers could refer when setting up a (imaging) study.
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http://dx.doi.org/10.1093/ehjci/jeaa314DOI Listing
December 2020

Native Anatomy and Genetic Diagnoses Have a Significant Impact on Long-term Outcomes for Patients With Tetralogy of Fallot.

Can J Cardiol 2020 Dec 9. Epub 2020 Dec 9.

Division of Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.cjca.2020.12.003DOI Listing
December 2020

Anatomic Concordance of Neonatologist-Performed Echocardiography as Part of Hemodynamics Consultation and Pediatric Cardiology.

J Am Soc Echocardiogr 2021 Mar 18;34(3):301-307. Epub 2020 Nov 18.

Department of Pediatrics, University of Iowa, Iowa City, Iowa; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada; Department of Internal Medicine, University of Iowa, Iowa City, Iowa. Electronic address:

Background: Targeted neonatal echocardiography (TnECHO) performed by neonatologists as part of a hemodynamics consultation is increasingly being used in neonatal intensive care units. To minimize delays in obtaining physiologic data, first echocardiograms may be obtained by the neonatal hemodynamics team and reviewed afterward by a pediatric cardiologist. This practice has not been systematically evaluated. The aim of this study was to compare concordance between anatomic findings on TnECHO and pediatric cardiology reports.

Methods: This was a retrospective evaluation of 339 infants at low risk for congenital heart disease (CHD) admitted to two large referral centers with established neonatal hemodynamics programs who underwent comprehensive TnECHO as their first postnatal echocardiographic examinations. The protocol included comprehensive imaging of intracardiac anatomy, outflow tract concordance and integrity, aortic arch anatomy, pulmonary vein location and flow, and transitional shunts. The hemodynamics consultation note was compared with the cardiology report to determine anatomic concordance or major or minor discrepancies in all first studies.

Results: Anatomic concordance occurred in 97.9% (κ = 0.862; 95% CI, 0.762-0.962; P < .001). There were seven minor discrepancies (small muscular ventricular septal defects and coronary fistulas). The index population included 23 infants (6.7%) with CHD, of whom only one (0.3%) had a ductal-dependent lesion (coarctation of the aorta) which was correctly identified by both teams.

Conclusions: The rate of major CHD in patients considered eligible for hemodynamics consultation was low, and there was high diagnostic concordance between trained neonatal hemodynamics specialists and pediatric cardiology. First echocardiograms obtained by subspecialty neonatologists may provide imaging of sufficient quality to evaluate a critically unwell neonate with low suspicion for critical CHD lesions. These results should not be extrapolated to infants in whom CHD is suspected. This study highlights the importance of formalized, rigorous, and standardized training for neonatologists with hemodynamics expertise who perform timely assessments using TnECHO.
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http://dx.doi.org/10.1016/j.echo.2020.11.005DOI Listing
March 2021

Vascular ring anomaly in a patient with phosphomannomutase 2 deficiency: A case report and review of the literature.

JIMD Rep 2020 Nov 19;56(1):27-33. Epub 2020 Aug 19.

Department of Clinical Genomics Mayo Clinic Rochester Minnesota USA.

Background: Congenital disorders of glycosylation (CDG) are a group of metabolic disorders well known to be associated with developmental delay and central nervous system anomalies. The most common CDG is caused by pathogenic variants in the phosphomannomutase 2 gene (), which impairs one of the first steps of N-glycosylation and affects multiple organ systems. Cardiac involvement can include pericardial effusion, cardiomyopathy, and arrhythmia, while an association with cardiovascular congenital anomalies is not well studied.

Case Summary: We report a 6-year-old individual who initially presented with inverted nipples, developmental delay, and failure to thrive at 3 months of age. At 4 months, due to feeding problems, swallowing exam and echocardiography were performed which revealed a vascular ring anomaly based on a right aortic arch and aberrant left subclavian artery. Subsequent whole exome gene sequencing revealed two pathogenic PMM2-CDG variants (E139K/R141H) and no known pathogenic mutations related to congenital heart defect (CHD).

Discussion: This is the first report of vascular ring anomaly in a patient with PMM2-CDG. We conducted a literature review of PMM2-CDG patients with reported CHD. Of the 14 patients with PMM2-CDG and cardiac malformation, the most common CHD's were tetralogy of Fallot, patent ductus arteriosus, and truncus arteriosus. The potential important link between CDG and CHD is stressed and discussed. Furthermore, the importance of multidisciplinary care for CDG patients including early referral to pediatric cardiologists is highlighted.
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http://dx.doi.org/10.1002/jmd2.12160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653259PMC
November 2020

Calibration of an Electrical Analog Model of Liver Hemodynamics in Fontan Patients.

J Biomech Eng 2020 Nov 10. Epub 2020 Nov 10.

Department of Mechanical and Industrial Engineering, Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; 5 King's College Road, Toronto, ON M5S 3G8.

Fontan associated liver disease is a common complication in patients with Fontan circulation, who were born with a single functioning heart ventricle. The hepatic venous pressure gradient (HVPG) is used to assess liver health and is a surrogate measure of the pressure gradient across the entire liver (portal pressure gradient). However, it is thought to be inaccurate in Fontan patients. The main objectives of this study were (1) to apply an existing detailed lumped parameter model of the liver to Fontan patients using patient-specific clinical data and (2) to determine whether HVPG is a suitable measurement of portal pressure gradients in these patients. An existing lumped parameter model of the liver blood circulation was applied and tuned to simulate patient-specific liver hemodynamics. Geometries were collected from seven adult Fontan patients and used to evaluate model parameters. The model was solved and tuned using waveform measurements of flows, inlet and outlet pressures. The predicted ratio of portal to hepatic venous pressures is comparable to in vivo measurements. The results confirmed that HVPG is not suitable for Fontan patients, as it would underestimate the portal pressures gradient by a factor of 3 to 4. Our patient-specific liver model provides an estimate of the pressure drop across the liver, which differs from the clinically used metric HVPG. This work represents a first step towards models suitable to assess liver health in Fontan patients and improve its long-term management.
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http://dx.doi.org/10.1115/1.4049075DOI Listing
November 2020

Blood Flow Imaging with Ultrafast Doppler.

J Vis Exp 2020 10 14(164). Epub 2020 Oct 14.

Translational Medicine Department, The Hospital for Sick Children, PGCRL Research Institute; The Labatt Family Heart Centre, Department of Pediatric, The Hospital for Sick Children, University of Toronto; Medical Biophysics Department, University of Toronto;

The pulsed-Doppler effect is the main technique used in clinical echography to assess blood flow. Applied with conventional focused ultrasound Doppler modes, it has several limits. Firstly, a finely tuned signal filtering operation is needed to distinguish blood flows from surrounding moving tissues. Secondly, the operator must choose between localizing the blood flows or quantifying them. In the last two decades, ultrasound imaging has undergone a paradigm shift with the emergence of ultrafast ultrasound using unfocused waves. In addition to a hundredfold increase in framerate (up to 10000 Hz), this new technique also breaks the conventional quantification/localization trade-off, offering a complete blood flow mapping of the field of view and a simultaneous access to fine velocities measurements at the single-pixel level (down to 50 µm). This data continuity in both spatial and temporal dimensions strongly improves the tissue/blood filtering process, which results in an increase sensitivity to small blood flow velocities (down to 1 mm/s). In this method paper, we aim to introduce the concept of ultrafast Doppler as well as its main parameters. Firstly, we summarize the physical principles of unfocused wave imaging. Then, we present the Doppler signal processing main steps. Particularly, we explain the practical implementation of the critical tissue/blood flow separation algorithms and on the extraction of velocities from these filtered data. This theoretical description is supplemented by in vitro experiences. A tissue phantom embedding a canal with flowing blood-mimicking fluid is imaged with a research programmable ultrasound system. A blood flow image is obtained and the flow characteristics are displayed for several pixels in the canal. Finally, a review of in vivo applications is proposed, showing examples in several organs such as carotids, kidney, thyroid, brain and heart.
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http://dx.doi.org/10.3791/61838DOI Listing
October 2020

Cardiac Function and Ventricular Interactions in Persistent Pulmonary Hypertension of the Newborn.

Pediatr Crit Care Med 2021 Feb;22(2):e145-e157

Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Objectives: The aim of this study was to use a comprehensive imaging protocol to identify echocardiographic correlations of right and left ventricular size, function, and hemodynamics in neonates with persistent pulmonary hypertension of newborn and describe their relationship with key clinical variables.

Design: Retrospective case-control echocardiography-based study of persistent pulmonary hypertension of newborn.

Setting: A tertiary neonatal ICU in Canada.

Patients: Forty-nine neonates (gestational age ≥ 35 wk old) diagnosed with persistent pulmonary hypertension of newborn within first 3 days after birth and 50 age-matched controls.

Interventions: None.

Measurements And Main Results: The echocardiographic measurements comprised of right ventricular and left ventricular functional markers, including tricuspid annular plane systolic excursion, fractional area change, tissue Doppler imaging, and deformation imaging. Sample size was based on detecting an intergroup difference of 10% in tricuspid annular plane systolic excursion, which was considered the primary outcome. Linear correlations between the right and left ventricular indices, as well as their association with the outcome of death or extracorporeal membrane oxygenation were evaluated. Persistent pulmonary hypertension of newborn was associated with lower tricuspid annular plane systolic excursion (6.81 ± 1.92 vs 9.25 ± 1.30 mm), right-ventricular global longitudinal strain (16.9% ± 5.4% vs -21.6% ± 4.6%); left ventricular ejection fraction (49% ± 7% vs 55% ± 6%), left ventricular global longitudinal strain (-16.7% ± 3.3% vs -21.4% ± 2.0%) (all p < 0.01). Right and left ventricular diastolic and global function was also lower in persistent pulmonary hypertension of newborn, with more pronounced changes seen for the right ventricle. Moderate-to-strong linear correlations were observed between the right and left ventricular functional markers, with right ventricular global longitudinal strain and left ventricular global longitudinal strain being the strongest (r = 0.8). Within persistent pulmonary hypertension of newborn group, hypoxic ischemic encephalopathy was associated with lower right and left ventricular systolic and right ventricular diastolic performance. Tricuspid annular plane systolic excursion (p =0.08) and left ventricular systolic velocity (p = 0.09) tended to be lower in patients who subsequently died/needed extracorporeal membrane oxygenation.

Conclusions: Persistent pulmonary hypertension of newborn is characterized by global cardiac dysfunction, involving both the right and left ventricles, with significant interventricular functional correlation. Cardiac dysfunction early in disease course may identify patients at highest risk of adverse outcome.
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http://dx.doi.org/10.1097/PCC.0000000000002579DOI Listing
February 2021

Non-invasive imaging techniques to assess myocardial perfusion.

Expert Rev Med Devices 2020 Nov 22;17(11):1133-1144. Epub 2020 Oct 22.

Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto , Toronto, ON, Canada.

Introduction: Coronary artery disease affecting myocardial perfusion continues to be the leading cause of cardiovascular morbidity and mortality worldwide. While invasive evaluation based on coronary angiography and flow measurements still is considered the reference technique for assessing myocardial perfusion, technological evolutions in noninvasive imaging techniques resulted in them playing a more important role in assessing myocardial perfusion influencing therapeutic decision-making and prognostication.

Areas Covered: Different imaging modalities are used to evaluate coronary perfusion, including echocardiography, coronary computerized tomography scan, magnetic resonance imaging, and nuclear myocardial perfusion imaging. Through a combination of different techniques, it is possible to describe coronary artery anatomy and the diameter of the epicardial vessels but more recently also of the coronary microcirculation. Quantification of myocardial perfusion is feasible both at baseline and during pharmacological or physiological stress.

Expert Opinion: The objective of this state-of-the-art paper is to review the recent evolutions in imaging methods to estimate myocardial perfusion and to discuss the diagnostic strengths and limitations of the different techniques. The new ultrasound technologies and the hybrid approaches seem to be the future is these fields.
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http://dx.doi.org/10.1080/17434440.2020.1834844DOI Listing
November 2020

Right Ventricular Remodeling in Hypoplastic Left Heart Syndrome is Minimally Impacted by Cardiopulmonary Bypass: A Comparison of Norwood vs. Hybrid.

Pediatr Cardiol 2021 Feb 10;42(2):294-301. Epub 2020 Oct 10.

Division of Pediatric Cardiology, Stollery Children's Hospital, 8440 112 St NW, unit 4C2.36, Edmonton, AB, T6G2B7, Canada.

Right ventricular (RV) remodeling in hypoplastic left heart syndrome (HLHS) begins prenatally and continues through staged palliations. However, it is unclear if the most marked observed remodeling post-Norwood is secondary to cardiopulmonary bypass (CPB) exposure or if it is an adaptation intrinsic to the systemic RV. This study aims to determine the impact of CPB on RV remodeling in HLHS. Echocardiograms of HLHS survivors undergoing stage 1 Norwood (n = 26) or Hybrid (n = 20) were analyzed at pre- and post-stage 1, pre- and post-bidirectional cavo-pulmonary anastomosis (BCPA), and pre-Fontan. RV fractional area change (FAC), vector velocity imaging for longitudinal & derived circumferential deformation (global radial shortening (GRS) = peak radial displacement/end-diastolic diameter), and deformation ratio (longitudinal/ circumferential) were assessed. Both groups had similar age, clinical status and functional parameters pre-stage 1. No difference in RV size and sphericity at any stage between groups. RVFAC was normal (> 35%) throughout for both groups. Both Norwood and Hybrid patients had increased GRS (p = 0.0001) post-stage 1 and corresponding unchanged longitudinal strain, resulting in decreased deformation ratio (greater relative RV circumferential contraction), p = 0.0001. Deformation ratio remained decreased in both groups in subsequent stages. Irrespective of timing of the first CPB exposure, both Norwood and Hybrid patients underwent similar RV remodeling, with relative increase in circumferential to longitudinal contraction soon after stage 1 palliation. The observed RV remodeling in HLHS survivors were minimally impacted by CPB.
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http://dx.doi.org/10.1007/s00246-020-02482-0DOI Listing
February 2021

Remote ischemic conditioning counteracts the intestinal damage of necrotizing enterocolitis by improving intestinal microcirculation.

Nat Commun 2020 10 2;11(1):4950. Epub 2020 Oct 2.

Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, Canada.

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants with high mortality rate, indicating the need for precision treatment. NEC is characterized by intestinal inflammation and ischemia, as well derangements in intestinal microcirculation. Remote ischemic conditioning (RIC) has emerged as a promising tool in protecting distant organs against ischemia-induced damage. However, the effectiveness of RIC against NEC is unknown. To address this gap, we aimed to determine the efficacy and mechanism of action of RIC in experimental NEC. NEC was induced in mouse pups between postnatal day (P) 5 and 9. RIC was applied through intermittent occlusion of hind limb blood flow. RIC, when administered in the early stages of disease progression, decreases intestinal injury and prolongs survival. The mechanism of action of RIC involves increasing intestinal perfusion through vasodilation mediated by nitric oxide and hydrogen sulfide. RIC is a viable and non-invasive treatment strategy for NEC.
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http://dx.doi.org/10.1038/s41467-020-18750-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532542PMC
October 2020

Data describing child development at 6 years after maternal cancer diagnosis and treatment during pregnancy.

Data Brief 2020 Oct 21;32:106209. Epub 2020 Aug 21.

Center for Gynecologic Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.

This manuscript is an accompanying resource of the original research article entitled "Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy" and present data that compare the outcome of 6-year-old-children born to women diagnosed with cancer during pregnancy (with or without treatment during pregnancy) (study group) with children born after an uncomplicated pregnancy (control group). Oncological, obstetrical and neonatal data were collected. Neurodevelopment was examined by clinical evaluation and neuropsychological testing (including intelligence, attention and memory tests) and by general health and behavior questionnaires. Cardiac evaluation included electro- and echocardiography. Univariate analyses of covariance were used to investigate between-group differences. A subgroup analysis was performed in chemotherapy-exposed children versus controls and anthracycline-exposed versus controls. Additionally, the incidence of behaviour problems was compared to matched controls for children whose mothers died and for those with surviving mothers.
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http://dx.doi.org/10.1016/j.dib.2020.106209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479323PMC
October 2020

Does Surgical Treatment of Coarctation in Adults Result in Better Outcomes Compared With the Transcatheter Approach?

Authors:
Luc Mertens

JACC Cardiovasc Imaging 2020 09;13(9):1873-1874

Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jcmg.2020.05.020DOI Listing
September 2020

Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy.

Eur J Cancer 2020 10 25;138:57-67. Epub 2020 Aug 25.

Department of Oncology, KU Leuven, Leuven, Belgium; Center for Gynecologic Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Department of Obstetrics and Gynecology, Amsterdam UMC, Location Amsterdam Medical Center and University of Amsterdam, the Netherlands. Electronic address:

Background: Data on the long-term effects of prenatal exposure to maternal cancer and its treatment on child development are scarce.

Methods: In a multicenter cohort study, the neurologic and cardiac outcomes of 6-year-old children born to women diagnosed with cancer during pregnancy were compared with the outcome of children born after an uncomplicated pregnancy. Assessment included clinical evaluation, comprehensive neuropsychological testing, electrocardiography and echocardiography.

Results: In total, 132 study children and 132 controls were included. In the study group, 97 children (73.5%) were prenatally exposed to chemotherapy (alone or in combination with other treatments), 14 (10.6%) to radiotherapy (alone or in combination), 1 (0.8%) to trastuzumab, 12 (9.1%) to surgery alone and 16 (12.1%) to no treatment. Although within normal ranges, statistically significant differences were found in mean verbal IQ and visuospatial long-term memory, with lower scores in the study versus control group (98.1, 95% confidence interval [CI]: 94.5-101.8, versus 104.4, 95% CI: 100.4-108.4, P = 0.001, Q < 0.001 [Q refers to the false discovery rate adjusted P value], and 3.9, 95% CI: 3.6-4.3, versus 4.5, 95% CI: 4.1-4.9, P = 0.005, Q = 0.045, respectively). A significant difference in diastolic blood pressure was found, with higher values in chemotherapy-exposed (61.1, 95% CI: 59.0 to 63.2) versus control children (56.0, 95% CI 54.1 to 57.8) (P < 0.001, Q < 0.001) and in a subgroup of 59 anthracycline-exposed (61.8, 95% CI: 59.3 to 64.4) versus control children (55.9, 95% CI: 53.6 to 58.1) (P < 0.001, Q = 0.02).

Conclusions: Children prenatally exposed to maternal cancer and its treatment are at risk for lower verbal IQ and visuospatial long-term memory scores and for higher diastolic blood pressure, but other cognitive functions and cardiac outcomes were normal at the age of 6 years.

Clinical Trial Registration: The study is registered at ClinicalTrials.gov, NCT00330447.
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http://dx.doi.org/10.1016/j.ejca.2020.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532701PMC
October 2020

Outcomes after anomalous aortic origin of a coronary artery repair: A Congenital Heart Surgeons' Society Study.

J Thorac Cardiovasc Surg 2020 Sep 13;160(3):757-771.e5. Epub 2020 Apr 13.

Division of Cardiology, Department of Paediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada.

Objectives: It remains unclear when sudden cardiac event risk outweighs surgical risk for patients with anomalous aortic origin of a coronary artery. The Congenital Heart Surgeons' Society sought to characterize the surgical risks by determining the techniques, complications, and outcomes of repair.

Methods: Between January 2000 and September 2018, 682 patients with anomalous aortic origin of a coronary artery aged 30 years or less were enrolled. Demographic, morphologic, operative, imaging, and ischemia-related data were analyzed.

Results: There were 395 of 682 (57%) surgical patients (45 centers, median follow-up 2.8 years). In addition to primary repair (87% unroofing, 26% commissural manipulation), 13 patients had 15 coronary-related reoperations. Of 358 patients with pre/postoperative aortic insufficiency assessment, 27 (8%) developed new mild or greater aortic insufficiency postoperatively, and 7 (2%) developed new moderate or greater aortic insufficiency. Freedom from mild aortic insufficiency differed in those with versus without commissural manipulation (85%/91% at 6 months, 83%/90% at 1 year, and 77%/88% at 3 years, respectively) (P = .05). Of 347 patients with preoperative/postoperative ejection fraction, 6 (2%) developed new abnormal ejection fraction (<50%) within 30 days of surgery which persisted. Although 64 of 395 patients (16%) had preoperative ischemia, after surgery 51 of 64 patients (80%) no longer had ischemia (13 = new postoperative ischemia, P < .0001). Four patients died postoperatively (preoperatively 2 asymptomatic, 1 symptomatic, 1 in extremis). Composite surgical adverse event rates were 7% to 13% in the entire cohort (increasing/decreasing by presentation/anatomy/repair strategy).

Conclusions: Anomalous aortic origin of a coronary artery surgery may relieve ischemia with low mortality; however, it can result in a variety of important morbidities, varying by the group evaluated. Strategies avoiding commissural manipulation may decrease the risk of developing aortic insufficiency. Understanding these risks should inform surgical decision-making and support the need for standardized assessment and management.
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http://dx.doi.org/10.1016/j.jtcvs.2020.01.114DOI Listing
September 2020

Augmentation of pulmonary blood flow and cardiac output by non-invasive external ventilation late after Fontan palliation.

Heart 2021 Jan 6;107(2):142-149. Epub 2020 Jul 6.

Toronto Congenital Cardiac Center for Adults, Peter Munk Cardiac Center, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada

Objectives: Although a life-preserving surgery for children with single ventricle physiology, the Fontan palliation is associated with striking morbidity and mortality with advancing age. Our primary objective was to evaluate the impact of non-invasive, external, thoraco-abdominal ventilation on pulmonary blood flow (PBF) and cardiac output (CO) as measured by cardiovascular magnetic resonance (CMR) imaging in adult Fontan subjects.

Methods: Adults with a dominant left ventricle post-Fontan palliation (lateral tunnel or extracardiac connections) and healthy controls matched by sex and age were studied. We evaluated vascular flows using phase-contrast CMR imaging during unassisted breathing, negative pressure ventilation (NPV) and biphasic ventilation (BPV). Measurements were made within target vessels (aorta, pulmonary arteries, vena cavae and Fontan circuit) at baseline and during each ventilation mode.

Results: Ten Fontan subjects (50% male, 24.5 years (IQR 20.8-34.0)) and 10 matched controls were studied. Changes in PBF and CO, respectively, were greater following BPV as compared with NPV. In subjects during NPV, PBF increased by 8% (Δ0.20 L/min/m (0.10-0.53), p=0.011) while CO did not change significantly (Δ0.17 L/min/m (-0.11-0.23), p=0.432); during BPV, PBF increased by 25% (Δ0.61 L/min/m (0.20-0.84), p=0.002) and CO increased by 16% (Δ0.47 L/min/m (0.21-0.71), p=0.010). Following BPV, change in PBF and CO were both significantly higher in subjects versus controls (0.61 L/min/m (0.2-0.84) vs -0.27 L/min/m (-0.55-0.13), p=0.001; and 0.47 L/min/m (0.21-0.71) vs 0.07 L/min/m (-0.47-0.33), p=0.034, respectively).

Conclusion: External ventilation acutely augments PBF and CO in adult Fontan subjects. Confirmation of these findings in larger populations with longer duration of ventilation and extended follow-up will be required to determine sustainability of haemodynamic effects.
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http://dx.doi.org/10.1136/heartjnl-2020-316613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788264PMC
January 2021

Effect of anthracycline therapy on myocardial function and markers of fibrotic remodelling in childhood cancer survivors.

Eur Heart J Cardiovasc Imaging 2021 Mar;22(4):435-442

Department of Paediatrics, The Hospital for Sick Children, University of Toronto, 555 University Ave., Toronto, M5G 1X8, ON, Canada.

Aims: Anthracyclines are a cornerstone of paediatric cancer treatment. We aimed to quantify myocardial cardiac magnetic resonance (CMR) native T1 (NT1) and extracellular volume fraction (ECV) as markers of fibrosis in a cohort of childhood cancer survivors (CCS).

Methods And Results: A cohort of CCS in remission underwent CMR T1 mapping. Diastolic function was assessed by echocardiography. Results were compared to a cohort of normal controls of similar age and gender. Fifty-five CCS and 46 controls were included. Both groups had similar mean left ventricular (LV) NT1 values (999 ± 36 vs. 1007 ± 32 ms, P = 0.27); ECV was higher (25.6 ± 6.9 vs. 20.7 ± 2.4%, P = 0.003) and intracellular mass was lower (37.5 ± 8.4 vs. 43.3 ± 9.9g/m2, P = 0.02) in CCS. The CCS group had lower LV ejection fraction (EF) and LV mass index with otherwise normal diastolic function in all but one patient. The proportion of subjects with elevated ECV compared to controls did not differ between subgroups with normal or reduced LV EF (22% vs. 28%; P = 0.13) and no correlations were found between LVEF and ECV. While average values remained within normal range, mitral E/E' (6.6 ± 1.6 vs. 5.9 ± 0.9, P = 0.02) was higher in CCS. Neither NT1 nor ECV correlated with diastolic function indices or cumulative anthracycline dose.

Conclusions: There is evidence for mild diffuse extracellular volume expansion in some asymptomatic CCS; myocyte loss could be part of the mechanism, accompanied by subtle changes in systolic and diastolic function. These findings suggest mild myocardial damage and remodelling after anthracycline treatment in some CCS which requires continued monitoring.
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http://dx.doi.org/10.1093/ehjci/jeaa093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984732PMC
March 2021

Cardiovascular and abdominal flow alterations in adults with morphologic evidence of liver disease post Fontan palliation.

Int J Cardiol 2020 Oct 27;317:63-69. Epub 2020 May 27.

Joint Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada; Division of Cardiology, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Canada; Division of Pediatric Cardiology, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address:

Background: Although morphologic abnormalities in the liver are commonly encountered post Fontan palliation, the relationships between hepatic morphology, vascular flows, and clinical status remain incompletely understood. We therefore aimed to explore flow characteristics in hepatic and intestinal vessels and to examine cardiovascular associations with liver disease.

Methods: This was a retrospective study of adults post Fontan palliation undergoing clinically indicated cardiovascular magnetic resonance imaging (MRI). Patients were included if MRI flow quantification was available for cardiac, hepatic and intestinal vessels; patients were excluded if phase-contrast flow imaging was insufficient for analysis.

Results: Thirty patients were studied (median age at MRI 28.5 years [range 19-47]). Eighteen subjects (60%) were classified as having morphologic liver disease according to validated criteria based on available MRI imaging. Abdominal and cardiovascular flows were quantified. Patients with morphologic liver disease had a 41% reduction in superior mesenteric artery (211 ± 124 versus 358 ± 181 mL/min/m, p = .004), a 36% reduction in hepatic vein (496 ± 247 versus 778 ± 220 mL/min/m, p = .01), a 31% reduction in portal vein (399 ± 133 versus 580 ± 159 mL/min/m, p = .004), and an 18% reduction in Fontan pathway flows (1358 ± 429 versus 1651 ± 270 mL/min/m, p = .04) compared with the remaining population. Adverse cardiovascular events were not associated with morphologic liver disease.

Conclusion: Morphologic liver disease appears to be associated with flow alterations within the heart, liver and intestine post Fontan palliation. These novel observations suggest that a potential relationship exists between morphologic disease and vascular flows thereby providing further insights into the pathophysiology of liver disease in this high-risk population.
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http://dx.doi.org/10.1016/j.ijcard.2020.05.064DOI Listing
October 2020

New Comprehensive Reference Values for Arterial Vascular Parameters in Children.

J Am Soc Echocardiogr 2020 08 19;33(8):1014-1022.e4. Epub 2020 May 19.

Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; SickKids Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Background: Noninvasive measurements of vascular parameters can be used for the detection and risk stratification of cardiovascular diseases. Most vascular parameters are influenced by age and body size, but pediatric reference values are scarce and limited to a few parameters. The aim of this study was to develop pediatric reference values and Z score equations for a comprehensive set of vascular parameters.

Methods: A total of 292 healthy subjects aged 0 to 18 years were prospectively recruited. Stiffness index β, pressure-strain elastic modulus, common carotid intima-media thickness, brachial flow-mediated dilation, radial augmentation index, central and right arm peripheral artery pulse-wave velocities, and pulse-wave velocity ratio were assessed. Normalization for age and anthropometric variables was performed using parametric multivariate regression modeling. Z scores were assessed for heteroscedasticity, residual association with age and body size, and distribution.

Results: Multivariate regression models with various combinations of height, weight, and age were used to obtain Z scores that were independent of age and body size. There was no residual association between Z scores and body size, age, or body mass index. There was no significant departure from the normal distribution.

Conclusions: The authors present reference values and Z score equations for a comprehensive set of vascular parameters during childhood. Further studies are necessary to assess their usefulness in detecting the vascular signs of subclinical atherosclerosis and chronic diseases, including congenital heart disease.
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http://dx.doi.org/10.1016/j.echo.2020.03.001DOI Listing
August 2020

The right ventricular myocardial systolic-to-diastolic duration ratio in children after surgical repair of Tetralogy of Fallot.

J Appl Physiol (1985) 2020 06 21;128(6):1677-1683. Epub 2020 May 21.

Division of Cardiology, The Labatt Family Heart Centre, The Hospital for Sick Children and University of Toronto, Canada.

Right ventricular (RV) function impacts clinical outcomes after surgical repair of Tetralogy of Fallot (rTOF). However, assessment of RV function remains difficult. We investigated the RV myocardial systolic-to-diastolic (S/D) duration ratio derived from strain imaging time intervals to characterize RV myocardial performance, exploring its relation with peak oxygen consumption during exercise (V̇o) and cardiac magnetic resonance-derived RV dilation and function in rTOF. We retrospectively analyzed 76 children with rTOF and 42 normal controls. The RV myocardial S/D duration ratio was measured from RV global and regional 2D speckle tracking longitudinal strain. Time from QRS onset to peak systolic strain was defined as the systolic duration. The S/D duration ratio was calculated and corrected for heart rate (HR). Postsystolic shortening (PSS) duration was defined as shortening time after cessation of pulmonary systolic antegrade flow. The RV myocardial S/D duration ratio, corrected or uncorrected for HR, was significantly higher in rTOF vs. controls (1 ± 0.3 vs. 0.8 ± 0.2, = 0.004) in relation to prolonged PSS. The HR-corrected myocardial S/D duration ratio correlated weakly with RV ejection fraction (EF,  = -0.37, = 0.001) and V̇o ( = -0.32, = 0.042). In multiregression analysis, RV EF was independently associated with the myocardial S/D duration ratio. The RV myocardial S/D duration ratio is a parameter of RV myocardial performance and efficiency, incorporating elements of systolic and diastolic performance, mechanical dyssynchrony, and PSS. The S/D duration ratio is associated with exercise capacity and RV dysfunction in rTOF. This is the first study to assess right ventricular myocardial performance using the systolic-to-diastolic duration ratio derived from 2D strain. Seventy-six children with repaired Tetralogy of Fallot were evaluated. Echocardiographic data were correlated with cardiac magnetic resonance and peak oxygen consumption during exercise. The results show the right ventricular myocardial systolic-to-diastolic duration ratio incorporates systolic and diastolic performance, electromechanical dyssynchrony, and postsystolic shortening and is associated with exercise capacity in repaired Tetralogy of Fallot.
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http://dx.doi.org/10.1152/japplphysiol.00775.2019DOI Listing
June 2020

Relationship Between Left Ventricular Geometry and Invasive Hemodynamics in Pediatric Pulmonary Hypertension.

Circ Cardiovasc Imaging 2020 05 15;13(5):e009825. Epub 2020 May 15.

Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado, Aurora (D.A.B., S.S.P., D.D.I).

Background Ventricular septal flattening, frequently present in pulmonary hypertension (PH), can be quantified using eccentricity index (EI). EI has not been evaluated by concurrent echocardiography and cardiac catheterization and traditionally does not account for postsystolic septal flattening, often seen in PH. We evaluated left ventricular shape, including a novel measure of maximal EI to account for postsystolic septal flattening, to establish the relationship with concurrent invasive hemodynamics. Methods Echocardiography was performed at 2 institutions in 78 pediatric PH patients during cardiac catheterization and in 78 matched controls. From midpapillary parasternal short-axis views, EI and right-to-left ventricular diameter ratio were assessed. Results EI and right-to-left ventricular measures were significantly increased in PH compared with controls. Shape measures correlated with invasive hemodynamics and PH outcome measures (PH-related hospitalization, functional class, medical therapy escalation, and BNP [brain natriuretic peptide]). End-systolic EI of 1.16 best identified the presence of PH, whereas a maximal EI of 1.42 and 1.94 best identified half-systemic and systemic PH, respectively. A maximal EI of 1.27 was associated with an odds ratio of 16.16 (95% CI, 6.62-39.46) for PH-related hospitalization or escalation of therapy. Conclusions Using simultaneous echocardiography and catheterization in the largest study population to date, we demonstrate that EI and right-to-left ventricular ratio correlate with invasive hemodynamics and outcomes measures, and EI can accurately define those with clinically important PH. These measures strengthen the ability of echocardiography to identify and follow pediatric PH patients, especially in the absence of methods to quantify right ventricular systolic pressures.
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http://dx.doi.org/10.1161/CIRCIMAGING.119.009825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236425PMC
May 2020

Clinical validity of systemic arterial steal among extremely preterm infants with persistent patent ductus arteriosus.

J Perinatol 2021 Jan 11;41(1):84-92. Epub 2020 May 11.

Department of Paediatrics, Mount Sinai Hospital, Toronto, ON, Canada.

Objective: Investigate relevance of diastolic flow abnormalities in celiac trunk (aCT) and middle cerebral artery (aMCA) among preterms with persistent hemodynamically significant patent ductus arteriosus (phsPDA, diameter ≥ 1.5 mm, and age ≥ 7 days).

Study Design: Five hundred fifteen echocardiograms from 156 neonates born <28 weeks gestation age (GA) were analyzed retrospectively. Infants with aCT or aMCA at any time were compared with the rest. Separate comparisons were performed for aCT and aMCA. Primary outcome was composite of death, chronic lung disease (CLD), or necrotizing enterocolitis ≥ stage 2. Logistic regression was used to adjust for confounders.

Result: Mean (SD) weight and GA were 820(214) g and 25.2(1.3) weeks. aMCA, but not aCT, was associated with primary outcome [adjusted odds ratio 2.17, 95% CI: 1.01-4.67] and CLD [2.20 (0.99-4.87)].

Conclusion: aMCA may be a valid marker for defining the clinical significance of phsPDA in preterm neonates. aCeT may be of limited value in selecting patients for treatment.
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http://dx.doi.org/10.1038/s41372-020-0663-8DOI Listing
January 2021

Predictors of Bicuspid Aortic Valve-Associated Aortopathy in Childhood: A Report From the MIBAVA Consortium.

Circ Cardiovasc Imaging 2020 03 17;13(3):e009717. Epub 2020 Mar 17.

Division of Cardiology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Canada (M.G., R.R., C.M., S.M., Ch.-P.S.F., C.M., L.M.).

Background: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients.

Methods: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity of AS and AI, history of coarctation, and aortic dimensions. Associations were determined using multivariable regression analysis. A subset of patients undergoing aortic interventions (balloon dilation or Ross) were assessed longitudinally.

Results: Data were obtained from 2122 patients (68% male; median age 10.2 years). Fifty percent of patients had ascending aorta dilatation. Right and noncoronary cusp fusion, increasing AS and AI, and older age were independently associated with ascending aorta dilatation. A history of coarctation was associated with less ascending aorta dilatation. In patients with neither AS nor AI, 37% had ascending aorta dilatation (4% severe). No complications related to aortic dilatation occurred in this cohort. Aortic scores were determined, and a -score calculator was created for this population.

Conclusions: In this large pediatric cohort of patients with BAV, valve morphology, AS, and AI are independently associated with ascending aorta dilatation, suggesting that hemodynamic factors influence aortopathy. However, even in BAVs with no AS or AI, there is significant ascending aorta dilatation independent of valve morphology. Interventions that led to changes in degree of AI and AS did not seem to influence change in aortic dimensions. The current BAV cohort can be used as a reference group for expected changes in aortic dimensions during childhood.
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http://dx.doi.org/10.1161/CIRCIMAGING.119.009717DOI Listing
March 2020

The Cardiac Genome Clinic: implementing genome sequencing in pediatric heart disease.

Genet Med 2020 06 10;22(6):1015-1024. Epub 2020 Feb 10.

Ted Rogers Centre for Heart Research, Cardiac Genome Clinic, The Hospital for Sick Children, Toronto, ON, Canada.

Purpose: This study investigated the diagnostic utility of nontargeted genomic testing in patients with pediatric heart disease.

Methods: We analyzed genome sequencing data of 111 families with cardiac lesions for rare, disease-associated variation.

Results: In 14 families (12.6%), we identified causative variants: seven were de novo (ANKRD11, KMT2D, NR2F2, POGZ, PTPN11, PURA, SALL1) and six were inherited from parents with no or subclinical heart phenotypes (FLT4, DNAH9, MYH11, NEXMIF, NIPBL, PTPN11). Outcome of the testing was associated with the presence of extracardiac features (p = 0.02), but not a positive family history for cardiac lesions (p = 0.67). We also report novel plausible gene-disease associations for tetralogy of Fallot/pulmonary stenosis (CDC42BPA, FGD5), hypoplastic left or right heart (SMARCC1, TLN2, TRPM4, VASP), congenitally corrected transposition of the great arteries (UBXN10), and early-onset cardiomyopathy (TPCN1). The identified candidate genes have critical functions in heart development, such as angiogenesis, mechanotransduction, regulation of heart size, chromatin remodeling, or ciliogenesis.

Conclusion: This data set demonstrates the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test. The genetic heterogeneity will necessitate large-scale genomic initiatives for delineating novel gene-disease associations.
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http://dx.doi.org/10.1038/s41436-020-0757-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272322PMC
June 2020

Intraoperative echocardiographic coronary artery imaging in congenital and acquired heart disease.

Cardiol Young 2020 Feb;30(2):153-161

Division of Paediatric Cardiology, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Canada.

Transoesophageal and epicardial echocardiography are indispensible intraoperative imaging modalities to guide paediatric heart disease surgeries and influence surgical decision-making. A less well-described role of intraoperative imaging is its utility in evaluating coronary artery patency and flow. Focused two-dimensional, colour, and spectral Doppler imaging of the coronary arteries should be performed during surgeries involving coronary manipulation or re-implantation, or in cases where there is unexpected ventricular dysfunction or electrographic signs concerning for ischaemia. Intraoperative imaging allows for any anatomical issues to be detected and addressed promptly in the operating room. Imaging of the coronary arteries should identify unobstructed coronary ostia and proximal course without kinking, angulation, narrowing, or significant calibre change to suggest stenosis or extrinsic compression from neighbouring structures. The aim of this review is to highlight the usefulness of transoesophageal and epicardial echocardiography in evaluating coronary artery patency and flow, provide a how-to guide for optimal imaging, and to introduce a practical guideline to achieve best clinical practice.
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http://dx.doi.org/10.1017/S1047951120000116DOI Listing
February 2020

Blood Speckle-Tracking Based on High-Frame Rate Ultrasound Imaging in Pediatric Cardiology.

J Am Soc Echocardiogr 2020 04 24;33(4):493-503.e5. Epub 2020 Jan 24.

Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

Background: Flow properties play an important role in cardiac function, remodeling, and morphogenesis but cannot be displayed in detail with today's echocardiographic techniques. The authors hypothesized that blood speckle-tracking (BST) could visualize and quantify flow patterns. The aim of this study was to determine the feasibility, accuracy, and potential clinical applications of BST in pediatric cardiology.

Methods: BST is based on high-frame rate ultrasound, using a combination of plane-wave imaging and parallel receive beamforming. Pattern-matching techniques are used to quantify blood speckle motion. Accuracy of BST velocity measurements was validated using a rotating phantom and by comparing BST-derived inflow velocities with pulsed-wave Doppler obtained in the left ventricles of healthy control subjects. To test clinical feasibility, 102 subjects (21 weeks to 11.5 years of age) were prospectively enrolled, including healthy fetuses (n = 4), healthy control subjects (n = 51), and patients with different cardiac diseases (n = 47).

Results: The phantom data showed a good correlation (r = 0.95, with a tracking quality threshold of 0.4) between estimated BST velocities and reference velocities down to a depth of 8 cm. There was a good correlation (r = 0.76) between left ventricular inflow velocity measured using BST and pulsed-wave Doppler. BST displayed lower velocities (mean ± SD, 0.59 ± 0.14 vs 0.82 ± 0.21 m/sec for pulsed-wave Doppler). However, the velocity amplitude in BST increases with reduced smoothing. The clinical feasibility of BST was high, as flow patterns in the area of interest could be visualized in all but one case (>99%).

Conclusions: BST is highly feasible in fetal and pediatric echocardiography and provides a novel approach for visualizing blood flow patterns. BST provides accurate velocity measurements down to 8 cm, but compared with pulsed-wave Doppler, BST displays lower velocities. Studying blood flow properties may provide novel insights into the pathophysiology of pediatric heart disease and could become an important diagnostic tool.
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http://dx.doi.org/10.1016/j.echo.2019.11.003DOI Listing
April 2020

Parameters of Right Ventricular Function Reveal Ventricular-Vascular Mismatch as Determined by Right Ventricular Stroke Work versus Pulmonary Vascular Resistance in Children with Pulmonary Hypertension.

J Am Soc Echocardiogr 2020 02 10;33(2):218-225. Epub 2019 Dec 10.

Division of Cardiology, The Labatt Family Heart Center, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.

Background: Right ventricular (RV) failure, a determinant of outcomes in pulmonary hypertension (PH), occurs when the right ventricle cannot compensate for increased afterload. The authors showed that RV stroke work (RVSW) can be estimated in children with PH as the product of stroke volume and RV pressure and is related to adverse outcomes. The aim of this study was to test the hypothesis that ventricular-vascular (VV) mismatch (high afterload and low RVSW) is associated with echocardiographic measures of RV performance and adverse outcomes.

Methods: Invasive hemodynamic data and concurrent echocardiograms were reviewed. Fifty subjects with PH were included. Four groups were created by dividing the patients using median RVSW and median pulmonary vascular resistance. For each group, tricuspid annular plane systolic excursion, fractional area change, myocardial performance index, and anterior RV wall thickness were determined. Both major (i.e., death) and minor (i.e., worsening World Health Organization class) clinical outcomes were tabulated. Groups were compared using the Kruskal-Wallis or Fisher exact test.

Results: Patients in the high pulmonary vascular resistance/low RVSW cohort (VV mismatch) had the worst RV dysfunction: median tricuspid annular plane systolic excursion, 0.8 cm (interquartile range, 0.7-0.8 cm; P = .0002); median fractional area change, 0.29% (interquartile range, 0.27%-0.30%; P = .004); median myocardial performance index, 0.622 (interquartile range, 0.548-0.789; P = .0004). This group had the highest incidence of adverse outcomes: major events in 40%, minor events in 80%, and syncope in 60%.

Conclusion: VV mismatch in pediatric PH can be assessed using RVSW and pulmonary vascular resistance and is associated with RV performance and adverse events. RVSW increases in compensated high-afterload states and falls as the right ventricle fails to meet increased load; thus, VV matching status may be a sensitive predictor of outcomes in pediatric PH.
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http://dx.doi.org/10.1016/j.echo.2019.09.013DOI Listing
February 2020