Regionalization or Access to Care? A Joint Pediatric Heart Care Program That Achieves Both: One Program-Two Sites.

Background: Regionalization of care for children with congenital heart disease has been proposed as a method to improve outcomes. This has raised concerns about limiting access to care. We present the details of a joint pediatric heart care program (JPHCP) which utilized regionalization and actually improved access to care. Methods: In 2017, Kentucky Children's Hospital (KCH) launched the JPHCP with Cincinnati Children's Hospital Medical Center (CCHMC). This unique satellite model was the product of several years of planning, leading to a comprehensive strategy with shared personnel, conferences, and a robust transfer system; "one program-two sites." Results: Between March 2017 and the end of June 2022, 355 operations were performed at KCH under the auspices of the JPHCP. As of the most recent published Society of Thoracic Surgeons (STS) outcome report (through the end of June 2021), for all STAT categories, the JPHCP at KCH outperformed the STS overall in postoperative length of stay, and the mortality rate was lower than expected for the case mix. Of the 355 operations, there were 131 STAT 1, 148 STAT 2, 40 STAT 3, and 36 STAT 4 operations, with two operative mortalities: an adult undergoing surgery for Ebstein anomaly, and a premature infant who died from severe lung disease many months after aortopexy. Conclusions: With a select case mix, and by affiliating with a large volume congenital heart center, the creation of the JPHCP at KCH was able to achieve excellent congenital heart surgery results. Importantly, access to care was improved for those children at the more remote location utilizing this one program-two sites model.

Managing uncertainty in decision-making of common congenital cardiac defects.

Decision-making in congenital cardiac care, although sometimes appearing simple, may prove challenging due to lack of data, uncertainty about outcomes, underlying heuristics, and potential biases in how we reach decisions. We report on the decision-making complexities and uncertainty in management of five commonly encountered congenital cardiac problems: indications for and timing of treatment of subaortic stenosis, closure or observation of small ventricular septal defects, management of new-onset aortic regurgitation in ventricular septal defect, management of anomalous aortic origin of a coronary artery in an asymptomatic patient, and indications for operating on a single anomalously draining pulmonary vein. The strategy underpinning each lesion and the indications for and against intervention are outlined. Areas of uncertainty are clearly delineated. Even in the presence of "simple" congenital cardiac lesions, uncertainty exists in decision-making. Awareness and acceptance of uncertainty is first required to facilitate efforts at mitigation. Strategies to circumvent uncertainty in these scenarios include greater availability of evidence-based medicine, larger datasets, standardised clinical assessment and management protocols, and potentially the incorporation of artificial intelligence into the decision-making process.

Medical education and training within congenital cardiology: current global status and future directions in a post COVID-19 world.

Despite enormous strides in our field with respect to patient care, there has been surprisingly limited dialogue on how to train and educate the next generation of congenital cardiologists. This paper reviews the current status of training and evolving developments in medical education pertinent to congenital cardiology. The adoption of competency-based medical education has been lauded as a robust framework for contemporary medical education over the last two decades. However, inconsistencies in frameworks across different jurisdictions remain, and bridging gaps between competency frameworks and clinical practice has proved challenging. Entrustable professional activities have been proposed as a solution, but integration of such activities into busy clinical cardiology practices will present its own challenges. Consequently, this pivot towards a more structured approach to medical education necessitates the widespread availability of appropriately trained medical educationalists, a development that will better inform curriculum development, instructional design, and assessment. Differentiation between superficial and deep learning, the vital role of rich formative feedback and coaching, should guide our trainees to become self-regulated learners, capable of critical reasoning yet retaining an awareness of uncertainty and ambiguity. Furthermore, disruptive innovations such as "technology enhanced learning" may be leveraged to improve education, especially for trainees from low- and middle-income countries. Each of these initiatives will require resources, widespread advocacy and raised awareness, and publication of supporting data, and so it is especially gratifying that Cardiology in the Young has fostered a progressive approach, agreeing to publish one or two articles in each journal issue in this domain.

Atg5 knockdown induces age-dependent cardiomyopathy which can be rescued by repeated remote ischemic conditioning.

Altered autophagy is implicated in several human cardiovascular diseases. Remote ischemic conditioning (RIC) is cardioprotective in multiple cardiovascular injury models and modifies autophagy signaling, but its effect in cardiomyopathy induced by gene manipulation has not been reported. To investigate the cardiac effects of chronically reduced autophagy as a result of Atg5 knockdown and assess whether RIC can rescue the phenotype. Atg5 knockdown was induced with tamoxifen for 14 days in cardiac-specific conditional Atg5 flox mice. Autophagy proteins and cardiac function were evaluated by Western blot and echocardiography, respectively. RIC was induced by cyclical hindlimb ischemia and reperfusion using a tourniquet. RIC or sham procedure was performed daily during tamoxifen induction and, in separate experiments, chronically 3 times per week for 8 weeks. Cardiac responses were assessed by end of the study. Cardiac-specific knockdown of Atg5 reduced protein levels by 70% and was associated with a significant increase in mTOR, a reduction of LC3-II and increased upstream autophagy proteins including LC3-I, P62, and Beclin. The changes in biochemical markers were associated with development of an age-related cardiomyopathy during the 17-month follow-up indicated by increased heart weight body weight ratio, progressive decline in cardiac function, and premature death. RIC increased cardiac ATG5 and rescued some of the Atg5 knockdown-induced cardiomyopathy phenotype and associated morphological remodeling. We conclude that cardiac-specific Atg5 knockdown leads to the development of age-related cardiomyopathy. RIC reverses the molecular and structural phenotype when administered both acutely and chronically.

Left Atrial Strain in the Repaired Tetralogy of Fallot Population: Comparisons to Biventricular Function, Native T1 Values, Exercise Parameters and Healthy Controls.

BACKGROUND: Non-invasive imaging markers in patients with repaired tetralogy of Fallot (rTOF) are still being investigated to inform clinical decision making. Atrial function is a prognostic indicator in many acquired and congenital heart diseases. We sought to examine the relationship between cardiac MRI (CMR)-derived indices of left atrial (LA) function, native left ventricular (LV) T1 values, biventricular systolic function, and exercise capacity in rTOF. METHODS: Sixty-six patients with rTOF without prior pulmonary valve replacement who underwent CMR (median age 18.5 years) were identified. Twenty-one adult rTOF patients (age range 19-32 years) were compared with 20 age-matched healthy volunteers (age range 19-34 years). LA reservoir, conduit, and pump global longitudinal strain (GLS) and strain rate (SR) were determined by tissue tracking. Native LV T1 values were measured on rTOF patients. Pearson correlations were performed to determine bivariate associations. RESULTS: Adult rTOF patients had higher pump GLS, pump:conduit, and pump:reservoir GLS ratios, and lower conduit:reservoir GLS ratio, LV ejection fraction (EF), and right ventricular EF compared to controls (p < 0.001 for each comparison). LA conduit:reservoir GLS and pump:reservoir GLS had correlations to native LV T1 (ρ = 0.26, p = 0.03 and ρ = - 0.26, p = 0.03, respectively). LA reservoir SR had positive correlation to RV EF (ρ = 0.27, p = 0.03). There were no statistically significant correlations between LA function and exercise capacity. CONCLUSIONS: LA function is altered in adolescent and young adult patients with rTOF indicating worse diastolic function and relates to increasing native LV T1 values. Future studies are indicated to investigate the progression of adverse atrial-ventricular interactions and poor outcomes in this population.

Webinars reduce the environmental footprint of pediatric cardiology conferences.

BACKGROUND: Webinars have recently replaced in-person medical conferences, including paediatric cardiology conferences, given the COVID-19 pandemic. METHODS: With increasing environmental concerns, we analysed the differences between the environmental footprint of a paediatric cardiology webinar with a hypothetical conference. Travel data was collected, with assumptions made on the amount of computer use, internet use and accordingly the overall use of electricity for both forms of conference. Life Cycle Assessment methodology was used (OpenLCA and Ecovinvent v 3.7). RESULTS: We showed that the theoretical environmental impact of a virtual conference is significantly less (4 tons CO2 equivalent) than the traditional international face-to-face conference (192 tons CO2 equivalent). The life cycle assessment methodology showed that resource use for a face-to-face conference lasting 2.5 days for 1374 attendees is equivalent to 400 times what an average person would use in one year, the climate change and photochemical ozone formation approximately 250 times and the eutrophication terrestrial equivalent to 225 times. However, using carbon equivalent emissions to measure environmental harm from flying is an under estimate of the potential damage, when one considers the additional production of airplane contrails. Notwithstanding this, there is a 98% reduction in climate change impact when meetings are held virtually. CONCLUSIONS: While the virtual conference may never completely replace the traditional in-person paediatric cardiology conference, due to networking benefits, the significant theoretical benefits to the environment highlighted in this study, warrants consideration for the virtual conference taking a more common place in sustainable academia.

Non-invasive left ventricular myocardial work indices in healthy adolescents at rest.

Global myocardial work (GMW) provides a metric of left ventricular (LV) function and energy consumption. Its non-invasive assessment by echocardiography correlates with invasive measures and normal values have been reported in healthy adults. We aimed to establish normal values in a healthy adolescent population. Fifty-two healthy adolescents (mean age = 14.5 ± 2.0 years, range 11-19 years, 62% male) with normal echocardiograms were included. Brachial cuff blood pressure was obtained immediately following apical imaging in the supine position. Post-processing of echocardiograms for speckle tracking strain measurement and derivation of global myocardial work indices from LV pressure-strain loops was performed. The mean global work index (GWI) was 1802.0 ± 264.4 mmHg% with mean global work efficiency of 95.5 ± 1.1%. The mean global constructive work (GCW) was 2054.5 ± 297.3 mmHg%, and the mean global wasted work 83.8 ± 28.1 mmHg%. On multivariable analysis, there were significant associations between both GWI and GCW with systolic blood pressure (ß coefficient = 0.57, p < 0.001; ß coefficient = 0.67, p < 0.001 respectively) and LV global longitudinal strain (GLS) (ß coefficient = - 0.56, p < 0.001; ß coefficient = - 0.52, p < 0.001 respectively). There were no associations with any of the work indices with age, sex, body surface area, heart rate or LV ejection fraction. This study provides echocardiographic reference ranges for non-invasive indices of GMW in normal adolescents.

Prevalence of ICU Delirium in Postoperative Pediatric Cardiac Surgery Patients.

OBJECTIVES: The objective of this study was to determine the prevalence of ICU delirium in children less than 18 years old that underwent cardiac surgery within the last 30 days. The secondary aim of the study was to identify risk factors associated with ICU delirium in postoperative pediatric cardiac surgical patients. DESIGN: A 1-day, multicenter point-prevalence study of delirium in pediatric postoperative cardiac surgery patients. SETTING: Twenty-seven pediatric cardiac and general critical care units caring for postoperative pediatric cardiac surgery patients in North America. PATIENTS: All children less than 18 years old hospitalized in the cardiac critical care units at 06:00 on a randomly selected, study day. INTERVENTIONS: Eligible children were screened for delirium using the Cornell Assessment of Pediatric Delirium by the study team in collaboration with the bedside nurse. MEASUREMENT AND MAIN RESULTS: Overall, 181 patients were enrolled and 40% (n = 73) screened positive for delirium. There were no statistically significant differences in patient demographic information, severity of defect or surgical procedure, past medical history, or postoperative day between patients screening positive or negative for delirium. Our bivariate analysis found those patients screening positive had a longer duration of mechanical ventilation (12.8 vs 5.1 d; p = 0.02); required more vasoactive support (55% vs 26%; p = 0.0009); and had a higher number of invasive catheters (4 vs 3 catheters; p = 0.001). Delirium-positive patients received more total opioid exposure (1.80 vs 0.36 mg/kg/d of morphine equivalents; p < 0.001), did not have an ambulation or physical therapy schedule (p = 0.02), had not been out of bed in the previous 24 hours (p < 0.0002), and parents were not at the bedside at time of data collection (p = 0.008). In the mixed-effects logistic regression analysis of modifiable risk factors, the following variables were associated with a positive delirium screen: 1) pain score, per point increase (odds ratio, 1.3; 1.06-1.60); 2) total opioid exposure, per mg/kg/d increase (odds ratio, 1.35; 1.06-1.73); 3) SBS less than 0 (odds ratio, 4.01; 1.21-13.27); 4) pain medication or sedative administered in the previous 4 hours (odds ratio, 3.49; 1.32-9.28); 5) no progressive physical therapy or ambulation schedule in their medical record (odds ratio, 4.40; 1.41-13.68); and 6) parents not at bedside at time of data collection (odds ratio, 2.31; 1.01-5.31). CONCLUSIONS: We found delirium to be a common problem after cardiac surgery with several important modifiable risk factors.

Are e-learning Webinars the future of medical education? An exploratory study of a disruptive innovation in the COVID-19 era.

OBJECTIVE: This study investigated the impact of the Webinar on deep human learning of CHD. MATERIALS AND METHODS: This cross-sectional survey design study used an open and closed-ended questionnaire to assess the impact of the Webinar on deep learning of topical areas within the management of the post-operative tetralogy of Fallot patients. This was a quantitative research methodology using descriptive statistical analyses with a sequential explanatory design. RESULTS: One thousand-three-hundred and seventy-four participants from 100 countries on 6 continents joined the Webinar, 557 (40%) of whom completed the questionnaire. Over 70% of participants reported that they "agreed" or "strongly agreed" that the Webinar format promoted deep learning for each of the topics compared to other standard learning methods (textbook and journal learning). Two-thirds expressed a preference for attending a Webinar rather than an international conference. Over 80% of participants highlighted significant barriers to attending conferences including cost (79%), distance to travel (49%), time commitment (51%), and family commitments (35%). Strengths of the Webinar included expertise, concise high-quality presentations often discussing contentious issues, and the platform quality. The main weakness was a limited time for questions. Just over 53% expressed a concern for the carbon footprint involved in attending conferences and preferred to attend a Webinar. CONCLUSION: E-learning Webinars represent a disruptive innovation, which promotes deep learning, greater multidisciplinary participation, and greater attendee satisfaction with fewer barriers to participation. Although Webinars will never fully replace conferences, a hybrid approach may reduce the need for conferencing, reduce carbon footprint. and promote a "sustainable academia".

Myocardial fibrosis, diastolic dysfunction and elevated liver stiffness in the Fontan circulation.

INTRODUCTION: Single ventricle diastolic dysfunction and hepatic fibrosis are frequently observed in patients with a Fontan circulation. The relationship between adverse haemodynamics and end-organ fibrosis has not been investigated in adolescents and young adults with Fontan circulation. METHODS: Prospective observational study of Fontan patients who had a cardiac catheterisation. Cardiac MRI with T1 mapping was obtained to measure extracellular volume (ECV), a marker of myocardial fibrosis. Hepatic magnetic resonance elastography was performed to assess liver shear stiffness. Serum biomarkers of fibrosis including matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were measured. Very high ECV was defined as >30% and elevated serum biomarkers as >75th percentile for each biomarker. RESULTS: 25 Fontan patients (52% female) with mean age of 16.3±6.8 years were included. Mean ECV was 28%±5%. There was a significant correlation between ECV and systemic ventricular end-diastolic pressure (r=0.42, p=0.03) and between ECV and liver stiffness (r=0.45, p=0.05). Patients with elevated ECV demonstrated elevations in MMPs and TIMPs. Similarly, patients with elevated MMPs and TIMPs had greater liver stiffness compared with patients with normal levels of these biomarkers. CONCLUSIONS: In Fontan patients, cardiac magnetic resonance evidence of myocardial fibrosis is associated with diastolic dysfunction, increased liver stiffness and elevated circulating biomarkers of fibrosis. These findings suggest the presence of a profibrotic milieu, with end-organ implications, in some patients with Fontan circulation.

Modified Ventricular Global Function Index Correlates With Exercise Capacity in Repaired Tetralogy of Fallot.

Background Cardiac MRI (CMR) derived ventricular global function index (GFI), a ratio of stroke volume to the sum of mean ventricular cavity and myocardial volumes, has demonstrated improved prediction of clinical outcomes in adults with atherosclerotic disease over ejection fraction. We sought to assess CMR derived GFI and a novel modification that accounts for unique loading conditions in patients with repaired tetralogy of Fallot (rTOF) and determine its correlation with exercise performance. Methods and Results Seventy-five patients with rTOF who underwent CMR were identified. Clinical variables were recorded and biventricular GFI calculated. A right ventricular (RV) effective GFI (eGFI) was derived by incorporating effective stroke volume. Thirty-five pediatric patients were matched with 29 age-matched healthy controls. Twenty-five patients completed cardiopulmonary exercise tests within 6 months of CMR. Stepwise regression models were used to determine univariate and multivariable predictors of indexed and percent predicted peak VO2. Median age at CMR was 20 years (interquartile range, 13-28). Pediatric rTOF patients had lower RV eGFI (P < 0.001), RV ejection fraction (P=0.002), but higher indexed RV end-diastolic and end-systolic volumes (P < 0.001, P < 0.001) compared with controls. Univariate analysis demonstrated a correlation between indexed peak VO2 with RV eGFI (R2=0.32, P=0.004), but with neither RVGFI, RV ejection fraction, indexed RV volumes nor RV mass. RV eGFI remained significantly associated with indexed peak VO2 during multivariable modeling. Conclusions Reduced RV eGFI was associated with reduced exercise capacity in rTOF patients, while RV GFI, RV ejection fraction, indexed RV volumes and mass were not. Our modification of the GFI, RV eGFI, may be a valuable non-invasive marker of cardiac function in rTOF.

Ablation of miR-144 increases vimentin expression and atherosclerotic plaque formation.

It has been suggested that miR-144 is pro-atherosclerotic via effects on reverse cholesterol transportation targeting the ATP binding cassette protein. This study used proteomic analysis to identify additional cardiovascular targets of miR-144, and subsequently examined the role of a newly identified regulator of atherosclerotic burden in miR-144 knockout mice receiving a high fat diet. To identify affected secretory proteins, miR-144 treated endothelial cell culture medium was subjected to proteomic analysis including two-dimensional gel separation, trypsin digestion, and nanospray liquid chromatography coupled to tandem mass spectrometry. We identified 5 gel spots representing 19 proteins that changed consistently across the biological replicates. One of these spots, was identified as vimentin. Atherosclerosis was induced in miR-144 knockout mice by high fat diet and vascular lesions were quantified by Oil Red-O staining of the serial sectioned aortic root and from en-face views of the aortic tree. Unexpectedly, high fat diet induced extensive atherosclerosis in miR-144 knockout mice and was accompanied by severe fatty liver disease compared with wild type littermates. Vimentin levels were reduced by miR-144 and increased by antagomiR-144 in cultured cardiac endothelial cells. Compared with wild type, ablation of the miR-144/451 cluster increased plasma vimentin, while vimentin levels were decreased in control mice injected with synthetic miR-144. Furthermore, increased vimentin expression was prominent in the commissural regions of the aortic root which are highly susceptible to atherosclerotic plaque formation. We conclude that miR-144 maybe a potential regulator of the development of atherosclerosis via changes in vimentin signaling.

Heart University: a new online educational forum in paediatric and adult congenital cardiac care. The future of virtual learning in a post-pandemic world?

Online learning has become an increasingly expected and popular component for education of the modern-day adult learner, including the medical provider. In light of the recent coronavirus pandemic, there has never been more urgency to establish opportunities for supplemental online learning. Heart University aims to be "the go-to online resource" for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of paedagogical material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practising provider. In this manuscript, we review the aims, development, current offerings and standing, and future goals of Heart University.

Reduced biventricular contractility during exercise in adults with small, unrepaired ventricular septal defects: an echocardiographic study.

OBJECTIVES: Small ventricular septal defects are often considered to be without long-term haemodynamic consequences and so the majority remains unrepaired. However, we recently showed reduced functional capacity and altered right ventricular morphology in adults with small, unrepaired ventricular septal defects. The underlying mechanisms behind these findings remain unclear, and so, biventricular contractility during exercise was evaluated. METHODS: Adults with small, unrepaired ventricular septal defects and healthy controls were examined with echocardiography during supine bicycle exercise with increasing workload. Tissue velocity Doppler was used for evaluating isovolumetric acceleration and systolic velocities during exercise. RESULTS: In total, 34 patients with ventricular septal defects, a median shunt- ratio of 1.2 (26 ± 6 years), and 28 healthy peers (27 ± 5 years) were included. Right ventricular isovolumetric acceleration was lower in patients as compared with controls at rest (97 ± 40 vs 158 ± 43 cm/s2, P = 0.01) and at peak heart rate (222 ± 115 vs 410 ± 120 cm/s2, P < 0.01). Peak systolic velocities were similar at rest, but differed with exercise (13 ± 3 vs 16 ± 3 cm/s, P = 0.02). Left ventricular isovolumetric acceleration was lower in patients as compared with controls throughout the test (P < 0.01). Septal isovolumetric acceleration was similar at rest, but reduced during increasing exercise as compared with controls (220 ± 108 vs 303 ± 119 cm/s2, P = 0.03). Left ventricular isovolumetric acceleration was negatively correlated with the shunt- ratio, and right ventricular and septal peak systolic velocities were positively correlated with lower functional capacity. CONCLUSIONS: Altered biventricular contractility is present during exercise in adults with small, unrepaired ventricular septal defects. These results add to the growing number of studies showing that long-term outcome in unrepaired ventricular septal defects may not be benign.

Repeated Remote Ischemic Conditioning Reduces Doxorubicin-Induced Cardiotoxicity.

OBJECTIVES: This study investigated the cardioprotective effect of repeated remote ischemic preconditioning (rRIC) on doxorubicin-induced cardiotoxicity in mice. BACKGROUND: Doxorubicin is an effective chemotherapeutic agent for a wide range of tumor types but its use and dosing are limited by acute and chronic cardiotoxicity. Remote ischemic conditioning (RIC) is cardioprotective in multiple cardiovascular injury models, but the effectiveness of rRIC in doxorubicin-induced cardiotoxicity has not been fully elucidated. METHODS: rRIC was performed on mice before and after doxorubicin administration. Cardiac function was assessed by echocardiography and myocardial biology was tested by molecular approaches. RESULTS: Doxorubicin administration induced acute cardiotoxicity, as indicated by reduced cardiac function, reduced myocyte cross-section area and increased extracellular collagen deposition, increased circulating cardiac muscle damage markers, and decreased heart weight. Doxorubicin also adversely affected other organs, including the kidney, liver, and spleen, as evaluated by circulating markers or organ weight loss. rRIC not only abrogated doxorubicin-induced cardiotoxicity (left ventricular ejection fraction, doxorubicin 47.5 ± 1.1%, doxorubicin + rRIC 51.6 ± 0.7%, p = 0.017), but also was associated with multiorgan protection. Within the myocardium, rRIC attenuated doxorubicin-induced cardiomyocyte apoptosis, reduced inflammation, and increased autophagy signaling. CONCLUSIONS: rRIC may be a promising approach to reduce doxorubicin-induced cardiotoxicity.