Background Ex-situ heart perfusion (ESHP) improves donor heart preservation via provision of a semi-physiologic, controlled environment. Optimizing preservation capacity through ESHP is of great interest to expand the donor pool and overcome logistical challenges. However, devices are currently untailored to pediatric donor hearts. We sought to evaluate subnormothermic ESHP (sESPH) in comparison to static cold storage (SCS). Methods Juvenile Yorkshire pig hearts (∼20 kg) were procured and subject to 10 hours of sESHP (n = 6) or 6 hours of SCS in modified Del Nido solution (n = 5), then transplanted orthotopically into weight-matched recipients. Following 2 hours of reperfusion, echocardiography was conducted before pigs were euthanized and samples of the ventricles were collected for analysis. Immunofluorescence staining for vascular inflammation markers VCAM-1, ICAM-1, and E-selectin was conducted. Hematoxylin and eosin staining of the ventricles was conducted and reviewed by a pathologist blinded to the experimental groups and scored for contraction bands, edema formation, inflammation, and hemorrhage. Results By echocardiography, hearts from both groups regained acceptable biventricular functionality, with no difference in left ventricular ejection fraction and shortening fraction between groups (p > 0.05). No differences in histological damage scores were found between groups (p > 0.05). Immunofluorescence staining showed qualitatively lessened expression of all markers in the sESPH group. Conclusions sESPH appears to prolong out-of-body time of pediatric donor hearts, with non-inferior tissue and functional preservation compared to SCS. sESHP may lessen inflammatory burden over the course of the preservation period.

BACKGROUND:Cardiac allograft vasculopathy (CAV) is the leading cause of late graft loss in children after pediatric heart transplantation (HTx). Coronary angiography, the reference standard for diagnosis, is invasive and carries a risk of complications. Noninvasive echocardiographic methods to reliably identify CAV in children have not yet been defined. METHODS:This study assessed the utility of functional echocardiography (FE) in the diagnosis of CAV in children. We prospectively assessed all children (< 18 years old) post-HTx during routine clinical surveillance between 2005 and 2020. For this study, we compared patients diagnosed with CAV (angiographic ISHLT criteria) with transplanted children without CAV, with FE at the time of diagnosis (d-CAV) and 6-12 months before diagnosis (pre-CAV), and evaluated clinical risk factors. RESULTS:We identified 10 children with CAV and 11 matched controls (CON). Right ventricular longitudinal strain (RV LS) and strain rate (RV LSR) were reduced at d-CAV (d-CAV RV LS, 12.1% [9.2,16.1] vs. CON RV LS, 21.5% [18.2,25.7]; d-CAV RV LSR, 0.75%/s [0.48, 0.98] vs. CON RV LSR, 1.35%/s [0.95,1.50], p < 0.01 for all) and pre-CAV (pre-CAV RV LS, 17.3% [10.8,20.2] vs. CON RV LS, 21.5% [18.2,25.7]; pre-CAV RV LSR 0.95%/s [0.80,1.10] vs. CON RV LSR, 1.35%/s [0.95,1.50], p ≤ 0.05 for all). Patients with CAV were more likely to have class II donor-specific antibodies (p = 0.01). CONCLUSION:Right ventricle systolic strain parameters were reduced as early as 12 months prior to CAV diagnosis, while the left ventricle functional parameters remained preserved. FE of the right ventricle may be a useful noninvasive tool for early recognition of developing CAV in transplanted children.

Hypertensive heart disease and hypertrophic cardiomyopathy both lead to left ventricular hypertrophy despite differing in aetiology. Elucidating the correct aetiology of the presenting hypertrophy can be a challenge for clinicians, especially in patients with overlapping risk factors. Furthermore, drugs typically used to combat hypertensive heart disease may be contraindicated for the treatment of hypertrophic cardiomyopathy, making the correct diagnosis imperative. In this review, we discuss characteristics of both hypertensive heart disease and hypertrophic cardiomyopathy that may enable clinicians to discriminate the two as causes of left ventricular hypertrophy. We summarise the current literature, which is primarily focused on adult populations, containing discriminative techniques available via diagnostic modalities such as electrocardiography, echocardiography, and cardiac MRI, noting strategies yet to be applied in paediatric populations. Finally, we review pharmacotherapy strategies for each disease with regard to pathophysiology.

BACKGROUND:Echocardiography parameters of right ventricular (RV) dysfunction, fractional area change (RVFAC), and global longitudinal strain during the first interstage have been shown to be associated with death or transplantation in patients with HLHS. However, both parameters lack adequate discriminatory characteristics. This study sought to examine global post-systolic contraction (PSC), a marker of myocardial inefficiency, as a predictor of death or transplantation (Tx) in patients with classic hypoplastic left heart syndrome (HLHS). METHODS:We performed a post-hoc analysis of 62 prospectively recruited patients with HLHS prior to the bidirectional cavopulmonary anastomosis (BCPA) surgery. We measured RV function parameters: RVFAC, global longitudinal strain, strain rate, mechanical dispersion index (MDI), and PSC. For each parameter, the receiver operating characteristic analysis determined the optimal cut-offs for the primary endpoint of death/Tx, followed by a Kaplan-Meier analysis. Parameters interobserver variability testing was performed. RESULTS:Median follow-up from pre-BCPA echocardiogram was 7.4 years. HLHS with outcome of death/Tx (n = 14) had lower RVFAC, longitudinal strain and strain rate, and increased PSC when compared with survivors. PSC of >5% performed the best, with the greatest area under the curve 0.75, sensitivity 64% and specificity 83%, hazard ratio 5.54 (95% CI 1.63-18.66), for the primary endpoint of death/Tx. PSC and strain parameters had excellent reproducibility. CONCLUSION:Increased global post-systolic contraction during the first interstage is associated with an outcome of death or transplantation in the medium term follow up of patients with HLHS. PSC has a greater specificity and reproducibility than global longitudinal strain and RV FAC. Investigation into its use in clinical practice as a predictor of outcome is warranted.

The double-orifice tricuspid valve (DOTV) is a rare lesion. We present a series of three patients encountered at the Stollery Children's Hospital with a diagnosis of DOTV on 2D and/or 3D echocardiography. The patient's medical records are reviewed for presentation history, investigative findings, and clinical course. We discuss the cases in the context of a complete review of all literature documenting cases of DOTV. In the majority of cases, the lesion is relatively benign, with little change in valve function over the short to medium term, and outcomes are determined largely by significant concomitant heart defects.

BACKGROUND:The perinatal transition is characterized by acute changes in cardiac loading. Compared with normal newborn combined cardiac output (CCO), single right ventricular (RV) output of neonates with hypoplastic left heart syndrome (HLHS) is markedly greater. The aim of this study was to examine the mechanisms of cardiac adaptation that facilitate this perinatal transition from late fetal to early neonatal life in HLHS. METHODS:Prospectively recruited pregnancies complicated by fetal HLHS (n = 35) and healthy control subjects (Ctrl; n = 17) underwent serial echocardiography in late gestation (38 ± 1 weeks) and 6, 24, and 48 hours after birth. Cardiac function was assessed using conventional, Doppler tissue, and speckle-tracking echocardiography. RESULTS:Term fetuses with HLHS had RV output comparable with Ctrl CCO via higher stroke volume. Compared with both left ventricular and RV indices of Ctrl, they exhibited globular and dilated right ventricles with reduced relative wall thickness (0.40 ± 0.08 vs 0.49 ± 0.10, P < .01), increased Tei index' (HLHS vs Ctrl left ventricle/Ctrl right ventricle: sphericity index, 0.9 ± 0.25 vs 0.5 ± 0.10/0.6 ± 0.11; RV area index, 28 ± 6 vs 15 ± 3/17 ± 5 cm2/m2; Tei index', 0.65 ± 0.11 vs 0.43 ± 0.07/0.45 ± 0.09; P < .0001 for all). Neonates with HLHS generated elevated RV cardiac output compared with Ctrl CCO via higher heart rate and stroke volume, with further RV dilatation, increased longitudinal systolic strain at 48 hours (-17 ± 4% vs -14 ± 3%/ 14 ± 5%) with reduced circumferential and rotational myocardial deformation and altered diastolic function. Neonates with HLHS also demonstrated right atrial enlargement with increased longitudinal strain: 6 hours (33 ± 12% vs 26 ± 6%), 24 hours (37 ± 15% vs 26 ± 13%), and 48 hours (38 ± 11% vs 24 ± 13%) (P < .0001). CONCLUSIONS:Term fetuses with HLHS exhibit altered RV geometry and RV systolic and diastolic functional parameters. After birth, further alterations in these cardiac parameters likely reflect adaptation to acutely altered RV loading from increasing cardiac output and pulmonary artery flow demands.

BACKGROUND:Children with a Fontan operation represent a unique form of congenital heart disease (CHD) that requires multiple cardiac surgeries and procedures with an uncertain long-term outcome. Given the rarity of the types of CHD that require this procedure, many children with a Fontan do not know any others like them.METHODS:With the cancelation of medically supervised heart camps due to the COVID-19 pandemic, we have organized several physician-led virtual day camps for children with a Fontan operation to connect with others in their province and across Canada. The aim of this study was to describe the implementation and evaluation of these camps via the use of an anonymous online survey immediately after the event and reminders on days 2 and 4 postevent.RESULTS:Fifty-one children have participated in at least 1 of our camps. Registration data showed that 70% of participants did not know anyone else with a Fontan. Postcamp evaluations showed that 86% to 94% learned something new about their heart and 95% to 100% felt more connected to other children like them.CONCLUSION:We have demonstrated the implementation of a virtual heart camp to expand the support network for children with a Fontan. These experiences may help to promote healthy psychosocial adjustments through inclusion and relatedness.

Introduction: Tricuspid valve (TV) regurgitation in Hypoplastic Left Heart Syndrome (HLHS) increases the risk of death/transplantation by 2 to 3 times. Abnormalities in TV annular shape, leaflets expansion and subvalve apparatus position, have been associated in HLHS with subsequent tricuspid regurgitation (TR). As TV morphological variation is increasingly recognized, its role on tricuspid valve function remains unknown. This study aims to describe and examine the relationship between the TV leaflet morphologies in HLHS and its association with TV repair. Methods: Cross sectional study of selected 38 “classic” HLHS patients from a prospective longitudinal 3DE study of HLHS TV. TV leaflet morphology from 3DE datasets were reviewed (S.Z and N.S.K) blinded to TR grade. We adapted a previously proposed nomenclature to describe the TV leaflets (Figure 1). Using the Chi-squared test, we compared the frequencies of TV morphological types of HLHS with mild or less TR (n = 23) vs. HLHS who had TV repair (n = 15) at latest follow up. Results: Incidence of TV morphological type is summarized in Figure 2. Bi-leaflet TV was the second most common, followed by bi-leaflet with a cleft. When comparing HLHS with mild or less TR vs. HLHS with TVR, only 1 of 9 bi-leaflet TV had subsequent TVR, while all bi-leaflet TV with a cleft, underwent TVR (p<0.05). Conclusion: HLHS has considerable TV leaflet variations with bi-leaflet TV being the second most common variation. While bi-leaflet TV is more likely to be found in a competent TV, those with a bi-leaflet TV with a cleft, all required TVR. Bi-leaflet TV with a cleft, warrants further study to assess its relationship and relative role with TVR.

Objective Past studies of fetal tetralogy of fallot (ToF) have reported extra-cardiac anomalies (ECAs) in 17%-45%, genetic syndromes in as low as 20% and poor postnatal outcomes. This study sought to examine these factors in a contemporary cohort. Methods A retrospective review examining 83 fetuses with ToF diagnosed 2012-2019. Referral indication, ToF subtype, additional cardiac, extra-cardiac and genetic diagnoses, pregnancy outcomes and survival were documented. Results The mean gestational age at diagnosis was 23 +/- 4 weeks. Of 94% (78/83) with genetic testing (GT), 30% (23/78, 95%CI 21%-40%) had genetic anomalies (GA), including Trisomy 21 (39%, 9/23), 22q11 deletion (35%, 8/23), Trisomy 13 or 18 (17%, 4/23) and 9% (2/23) others. A further 4% (3/78) had VACTERL association. Forty-one percent (34/83, 95%CI 31%-52%) had >= 1 major ECA of whom 41% (14/34) also had a genetic anomaly. Outcomes: 22% (18/83) pregnancy termination, 5% (4/83) intrauterine death and 72% (60/83) live birth. Of live births, 3% (2/60) experienced neonatal death, 7% late death (4/60) and 90% (54/60) were alive at last follow-up (mean age 3.5 +/- 2.4 years). Conclusion In a cohort of fetuses with ToF and high rates of GT, compared to previous reports, GA were more common and there were similar rates of ECAs.

Background: Up to 15% of patients with partial Atrioventricular Septal Defects ( p AVSD) require re-repair of the Left AtrioVentricular Valve (LAVV), with 30% having significant regurgitation. Previous qualitative studies suggest abnormalities in papillary muscles, shortened chordae and thick chords as features associated with LAVVR. We aim to quantitatively assess the sub valvar apparatus in pAVSD using three-Dimensional Echocardiography (3DE) for its association with LAVVR. Hypothesis: We hypothesize that larger papillary muscle and chordal thickness in patients with p AVSD is associated with post-operative LAVVR. Methods: This is a prospective study between 2006 and 2018, of pAVSD aged 0-18 years. All underwent 3DE under sedation using X7-2 probe on a Philips iE33 ultrasound system. Utilizing offline QLAB multi-planar reconstruction (v.10.8.5) we measured anterolateral (APM) and posteromedial papillary (PPM) muscle length; cross sectional area and circumference; chordal length and thickness in mid systole. We measured post-operative vena contracta and LAVV diameter in Apical 4 chamber using 2D color Doppler. Cohort was divided into patients with significant post-operative LAVVR vs. controls based on LAVV vena contracta/LAVV annulus ratio cut off >0.25 (greatest one-third of cohort), LAVVR (n=22) and Controls (n=44). All variables are indexed to Body Surface Area, expressed as median [interquartile range] or mean (standard deviation). Results: LAVVR group were younger at initial surgery, had larger papillary muscles and thicker chords. Table 1 summarizes the variables for Control and LAVVR. Eighteen patients had LAVV re-repair, 14 (63%) were in LAVVR group and 4 (9%) in Controls. Median follow up was 1.5 years. Median time to re-repair was 1.3 years. Conclusion: p AVSD patients with a greater risk of post-operative LAVVR and subsequently re-repair were younger at first repair and had larger papillary muscles length, circumference and thicker chords.

Background: Tricuspid valve regurgitation (TR) is a risk factor for morbidity and mortality in children with hypoplastic left heart syndrome (HLHS). Surgical tricuspid valve (TV) repair is common, but durable repair remains challenging. The aim of this study was to examine mechanisms of TR requiring surgery, features associated with unsuccessful repair, and TV changes after surgical repair. Methods: Thirty-six patients with HLHS requiring TV repair (TVR) and 36 matched control subjects with HLHS were assessed using two-dimensional and three-dimensional echocardiography. Using three-dimensional echocardiography, TV coordinates from the annulus, leaflet, and ventricle were used to measure annular, leaflet, prolapse, and tethering values and anterior papillary muscle angle. TR grade and ventricular size, function, and shape were assessed using two-dimensional echocardiography. Results: Patients requiring TVR had greater total leaflet prolapse, larger TV annular and leaflet areas, and flatter annuli, with no difference in tethering, coaptation index, or anterior papillary muscle angle. In patients with HLHS, successful TVR at follow-up (58%) was associated with preoperative total leaflet prolapse (especially posterior). Unsuccessful repair was associated with preoperative tethering of the septal leaflet. TVR in patients with HLHS caused a reduction of total annular and leaflet size and reduced prolapse and tethering of the posterior leaflet but did not affect anterior leaflet prolapse or septal leaflet tethering. Conclusions: Features associated with TVR include a flattened and dilated TV annulus with leaflet prolapse. The additional presence of a tethered septal leaflet before TVR is associated with significant postoperative TR. Current surgical techniques, predominantly posterior annuloplasty and commissuroplasty, adequately address annular size and posterior leaflet pathology, but not septal leaflet tethering. Individualized and innovative surgical techniques are vital to improve surgical repair success. (J Am Soc Echocardiogr 2021;34:1199-210.)

BACKGROUND:Fetuses of diabetic mothers develop left ventricular (LV) hypertrophy and are at increased long-term risk of cardiovascular disease. In our previous longitudinal study from midgestation to late infancy we showed persistence of LV hypertrophy and increased aortic stiffness compared with infants of healthy mothers, the latter of which correlated with third trimester maternal hemoglobin A1c. In the present study, we reexamined the same cohort in early childhood to determine if these cardiovascular abnormalities persisted.METHODS:Height, weight, and right arm blood pressure were recorded. A full functional and structural echocardiogram was performed with offline analysis of LV posterior wall and interventricular septal diastolic thickness (IVSd), systolic and diastolic function, and aortic pulse wave velocity. Vascular reactivity was assessed using digital thermal monitoring. Participants also completed a physical activity questionnaire.RESULTS:Twenty-five children of diabetic mothers (CDMs) and 20 children from healthy pregnancies (mean age, 5.6 ± 1.7 and 5.3 ± 1.3 years, respectively; P = not significant) were assessed. Compared with controls, IVSd z score was increased in CDMs (1.2 ± 0.6 vs 0.5 ± 0.3, respectively; P = 0.006), with one-fifth having a z score of more than +2.0. Aortic pulse wave velocity was increased in CDMs (3.2 ± 0.6 m/s vs 2.2 ± 0.4 m/s; P = 0.001), and correlated with IVSd z score (R 2 = 0.81; P = 0.001) and third trimester maternal A1c (R 2 = 0.65; P < 0.0001). Body surface area, height, weight, blood pressure, vascular reactivity, and physical activity scores did not differ between groups. Our longitudinal analysis showed that individuals with greater IVSd, and aortic stiffness in utero, early and late infancy also tended to have greater measures in early childhood (P < 0.001 and P < 0.0001, respectively).CONCLUSIONS:CDMs show persistently increased interventricular septal thickness and aortic stiffness in early childhood.

Introduction: Historically, prenatal detection of tetralogy of Fallot (ToF) was poor and around 60% had major extracardiac (ECA) or genetic anomalies. Recently, prenatal detection of ToF has improved, along with a wider range of genetic testing options. Knowledge of outcomes and risk of associated anomalies is crucial for prenatal counselling. We hypothesize that prenatal ToF now has a different risk profile for ECAs and genetic anomalies than previously reported. Methods: A retrospective study of all fetuses with a diagnosis of ToF in our Fetal Cardiology program from 2012-2019. ToF type double outlet right ventricle was excluded. Pre and postnatal charts and imaging reports were reviewed for ToF subtype, additional cardiac and non-cardiac diagnoses and outcomes. Results: Of 83 cases, 49 had standard ToF, 24 pulmonary atresia (14 with major collateral arteries, 10 without), and 10 absent pulmonary valve. There was ≥1 ECA in 41% (34/83), including 6% (5/83) with 2 and 4% (3/83) with 3. ECA sub-types were: 10 gastrointestinal, 8 neurological, 8 pulmonary, 7 renal, 4 musculoskeletal, and 8 others. Of 76 with genetic testing, 37% (28/76) had genetic anomalies (32% (9/28) Trisomy 21, 29% (8/28) 22q11 deletion, 7% (2/28) Trisomy 18, 7% (2/28) Trisomy 13, and 25% (7/28) other). Additional diagnoses: 4% (3/76) VACTERL spectrum, 1% (1/76) possible teratogenic effect. Right aortic arch was associated with 22q11 deletion (28% (7/25) vs 2% (1/51) p<0.001). ToF with atrioventricular septal defect (AVSD) was strongly associated with Trisomy 21 (100%, 3/3 tested). Those with ≥1 ECA were more likely to have a genetic abnormality (52% (17/33) vs 24% (9/37), p<0.05). Outcomes were: 22% (18/83) termination, 5% (4/83) intrauterine fetal deaths and 72% (60/83) livebirths, with 1 lost to follow-up. Of live births, there were 3% (2/60) neonatal and 7% (4/60) late deaths, and 90% (54/60) were alive at last follow-up (mean age 3.5±2.4 years). Conclusion: ECAs are less common in prenatally diagnosed ToF in the modern era, however the rate of genetic diagnoses is similar to previously published data. ToF with right aortic arch and ToF with AVSD in particular have strong genetic associations. Additionally, genetic diagnoses are more common in those with an ECA.

Heart conditions in which the tricuspid valve (TV) faces either increased volume or pressure stressors are associated with premature valve failure. Mechanistic studies to improve our understanding of the underlying pathophysiology responsible for the development of premature TV failure are lacking. Due to the inability to conduct these studies in humans, an animal model is required. In this manuscript, we describe the protocols for a novel chronic recovery infant piglet heart model for the study of changes in the TV when placed under combined volume and pressure stress. In this model, volume loading of the right ventricle and the TV is achieved through the disruption of the pulmonary valve. Then pressure loading is accomplished through the placement of a pulmonary artery band. The success of this model is assessed at four weeks post intervention surgery through echocardiography, intracardiac pressure measurement, and pathologic examination of the heart specimens.

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.

Heart conditions in which the tricuspid valve (TV) faces either increased volume or pressure stressors are associated with premature valve failure. Mechanistic studies to improve our understanding of the underlying pathophysiology responsible for the development of premature TV failure are lacking. Due to the inability to conduct these studies in humans, an animal model is required. In this manuscript, we describe the protocols for a novel chronic recovery infant piglet heart model for the study of changes in the TV when placed under combined volume and pressure stress. In this model, volume loading of the right ventricle and the TV is achieved through the disruption of the pulmonary valve. Then pressure loading is accomplished through the placement of a pulmonary artery band. The success of this model is assessed at four weeks post intervention surgery through echocardiography, intracardiac pressure measurement, and pathologic examination of the heart specimens.