Search

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.

This study describes the evolving in-hospital management strategies for neonates who are diagnosed with tetralogy of Fallot (ToF).The Pediatric Health Information System (PHIS) database was used to identify admitted patients aged 0 to 1 month old with ToF from 2010 through 2019; era 1, 2010 through 2014; and era 2, 2015 through 2019. International Classification of Diseases codes were used to identify related interventions that occurred during this admission but not necessarily as a neonate: full repair, systemic-to-pulmonary shunt, and percutaneous stent in the right ventricular outflow tract and/or patent ductus arteriosus.Among 6021 neonates diagnosed with ToF, 2030 (34%) underwent an intervention: 60% had total repair, 31% systemic-to-pulmonary shunt, and 9% percutaneous stent. In the no-intervention cohort, in-hospital mortality was 9%. In-hospital mortality between repair (6%), shunt (6%), and stent (3%) patients (P = .446) did not differ. Regarding regional practices, no intervention was most frequently used in the Midwest (69% vs 65% average for all other regions [avg], P = .075) while interventions overall were performed most frequently in the West (36% vs 33.5% avg, P = .075). Among the interventions, full repair was most frequent in the Northeast (76% vs 57% avg, P.001), shunt was most frequent in the Midwest (39% vs 28% avg, P.001), and stent was most frequent in the South (11% vs 7% avg, P = .083). Between eras 1 and 2, the type of intervention changed: full repair (52% vs 69%, P.001) and stent (1% vs 16%, P.001) increased, while shunt decreased (47% vs 15%, P.001).Although most neonates admitted with ToF are discharged with no intervention, more than one-third undergo some intervention with a 3% to 6% mortality. The proportion of these patients who undergo an intervention is unchanged during the past decade, but the types of intervention have changed, and significant regional differences exist.

More than 90% of patients with congenital heart disease (CHD) are nowadays surviving to adulthood and adults account for over two-thirds of the contemporary CHD population in Western countries. Although outcomes are improved, surgery does not cure CHD. Decades of longitudinal observational data are currently motivating a paradigm shift toward a lifespan perspective and proactive approach to CHD care. The aim of this review is to operationalize these emerging concepts by presenting new constructs in CHD research. These concepts include long-term trajectories and a life course epidemiology framework. Focusing on a precision health, we propose to integrate our current knowledge on the genome, phenome, and environome across the CHD lifespan. We also summarize the potential of technology, especially machine learning, to facilitate longitudinal research by embracing big data and multicenter lifelong data collection.

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. 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. 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

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 (β coefficient = 0.57, p

Ventricular septal defects (VSDs) have recently demonstrated poorer functional outcome with disrupted ventricular contractility during exercise in young patients. It is not known whether this will change with age. Therefore, echocardiography was performed in older patients with congenital VSDs, either surgically closed or unrepaired and all without Eisenmenger physiology, to compare functional outcomes with healthy peers. Transthoracic echocardiography was performed at rest and during supine bicycle exercise, with tissue velocity Doppler for assessment of primary end points: isovolumetric acceleration and systolic velocities. In total, 30 surgically closed VSDs (51 ± 8 years) with 30 healthy controls (52 ± 9 years) and 30 unrepaired VSDs (55 ± 12 years) with 30 matched controls (55 ± 10 years) were included. Surgical patients displayed lower right ventricular (RV) systolic and early diastolic-filling velocities compared with controls, p

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.

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.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s00395-021-00888-2.

Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.

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.

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 (β coefficient = 0.57, p 0.001; β coefficient = 0.67, p 0.001 respectively) and LV global longitudinal strain (GLS) (β coefficient = - 0.56, p 0.001; β 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.

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”.

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.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.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.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.

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 VO 2 . 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 VO 2 with RV eGFI ( R 2 =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 VO 2 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.

Common arterial trunk, or truncus arteriosus, is a rare form of congenital heart disease defined by the presence of an arterial trunk which arises from the ventricular mass through a common ventriculo-arterial junction and gives rise to the systemic, pulmonary, and coronary circulations. The anatomical variation and associated cardiac anomalies dictate the clinical presentation and specific surgical repair strategy. This chapter reviews a common presentation of a newborn with common arterial trunk, serving as the basis for discussion of the anatomical variation, physiology, resulting clinical presentation and preoperative management, surgical repair strategy, and outcomes.

Kawasaki disease is the most common acquired heart disease in children in developed countries. Coronary involvement is reported in 30% of patients with no treatment and decreases to 5% with intravenous immunoglobulin treatment. Given the significant risk for coronary involvement, understanding the long-term prognosis is paramount to guide outpatient follow-up and treatment. This chapter presents the case of a 20-month-old child with Kawasaki disease and giant coronary aneurysms. The chapter reviews the diagnostic criteria and coronary imaging aspects, delves into the treatment options and prognosis, including immunoglobulin treatment.

In this nation-wide cohort study we report the first long-term results of the association between having a atrial septal defects (ASD) on psychiatric disorders and use of psychotropic agents. Through population-based registries we included Danish individuals born before 1994 who received an ASD diagnosis between 1959and 2013. We used Cox proportional hazards regression and Fine and Grey competing risk regression to estimate the risk of receiving a psychiatric diagnosis and use of psychotropic medicine compared with a gender and age matched background population cohort. In 2,277 patients with a median follow-up from ASD diagnosis of 23.4 years (range 0.2 to 59.3 years) we found ASD patients to have a higher risk of psychiatric disorders (adjusted hazard ratio [HR]: 3.9; 95% confidence interval [CI] 3.4 to 4.5) compared with the comparison cohort and a cumulative incidence of using psychotropic agents 30 years after the ASD diagnosis of 47.4% (95% CI: 40.3 to 55.1) in the ASD patients and 25.5%, (95% CI: 23.5 to 27.8) in the comparison cohort. Diagnosis of the ASD before the age of 15 years (adjusted HR: 3.4; 95% confidence interval: 2.0 to 4.0) and surgical correction of the defect (HR: 1.5 (95% CI: 1.2 to 1.8), p

BACKGROUND: There are increasing reports of cardiac and exercise dysfunction in adults with small, unrepaired ventricular septal defects (VSDs). The primary aim of this study was to evaluate pulmonary function in adults with unrepaired VSDs, and secondly to assess the effects of 900 μg salbutamol on lung function and exercise capacity.METHODS: Young adult patients with small, unrepaired VSDs and healthy age- and gender-matched controls were included in a double-blinded, randomised, cross-over study. Participants underwent static and dynamic spirometry, impulse oscillometry, multiple breath washout, diffusion capacity for carbon monoxide, and ergometer bicycle cardiopulmonary exercise test.RESULTS: We included 30 patients with VSD (age 27 ± 6 years) and 30 controls (age 27 ± 6 years). Patients tended to have lower FEV1, 104 ± 11% of predicted, compared with healthy controls, 110 ± 14% (p = 0.069). Furthermore, the patient group had lower peak expiratory flow (PEF), 108 ± 20% predicted, compared with the control group, 118 ± 17% (p = 0.039), and showed tendencies towards lower forced vital capacity and increased airway resistance compared with controls. During exercise, the patients had lower oxygen uptake, 35 ± 8 ml/min/kg (vs 47 ± 7 ml/min/kg, p CONCLUSION: At rest, young adults with unrepaired VSDs are no different in pulmonary function from controls. However, when the cardiorespiratory system is stressed, VSD patients demonstrate significantly impaired minute ventilation and peak oxygen uptake, which may be early signs of parenchymal dysfunction and restrictive airway disease. These abnormalities were unaffected by the inhalation of salbutamol.

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., Central Illustration

Background Anthracycline cardiotoxicity can cause significant long-term morbidity in childhood cancer survivors (CCS), but many CCS do not manifest clinical symptoms until adulthood. The aims of this study were to characterize the dynamic myocardial response to exercise of CCS at long-term follow-up by combining semisupine bicycle exercise stress echocardiography with myocardial imaging techniques and to establish whether semisupine bicycle exercise stress echocardiography could identify CCS with abnormal exercise response. Methods This was a single-center prospective cross-sectional study. One hundred CCS and 51 control subjects underwent semisupine bicycle exercise stress echocardiography. Color Doppler tissue imaging peak systolic (s′) and diastolic (e′) velocities, myocardial acceleration during isovolumic contraction, and longitudinal strain were measured at rest and at incremental heart rates in the left ventricular (LV) lateral wall, basal septum, and right ventricle. The relationship with increasing heart rate was evaluated for each parameter by plotting the values against heart rate at each stage of exercise. Kernel density estimate was used to establish the normality of the individual CCS exercise responses. Results At rest, no significant differences were found for LV lateral wall, right ventricular (RV), and basal septal systolic and diastolic velocities between CCS and control subjects. Only septal e′ was lower in CCS. LV longitudinal strain was similar between groups, while RV longitudinal strain was lower in CCS. At peak exercise, LV lateral wall, RV, and septal s′ were not different between groups, while e′ were significantly lower in CCS. LV lateral wall and septal isovolumic acceleration were also reduced in CCS. LV longitudinal strain was different between groups, while RV longitudinal strain was similar. The dynamic response of Doppler tissue imaging velocities, isovolumic acceleration, and strain was similar between CCS and control subjects. Kernel density estimate analysis confirmed that most CCS responses were within the normal range. Conclusions At 10-year follow-up, anthracycline-treated CCS with normal baseline ejection fractions have LV and RV systolic and diastolic myocardial exercise response comparable with that of control subjects. Minor differences were observed between CCS and control subjects at rest and at peak exercise, but the dynamic response is within the normal range.

Objectives The purpose of this study was to describe how pediatric cardiac intensive care clinicians assess and manage delirium in patients following cardiac surgery. Design Descriptive self-report survey. Setting A web-based survey of pediatric cardiac intensive care clinicians who are members of the Pediatric Cardiac Intensive Care Society. Patient or subjects Pediatric cardiac intensive care clinicians (physicians and nurses). Interventions None. Measurement and main results One-hundred seventy-three clinicians practicing in 71 different institutions located in 13 countries completed the survey. Respondents described their clinical impression of the occurrence of delirium to be approximately 25%. Most respondents (75%) reported that their ICU does not routinely screen for delirium. Over half of the respondents (61%) have never attended a lecture on delirium. The majority of respondents (86%) were not satisfied with current delirium screening, diagnosis, and management practices. Promotion of day/night cycle, exposure to natural light, deintensification of care, sleep hygiene, and reorientation to prevent or manage delirium were among nonpharmacologic interventions reported along with the use of anxiolytic, antipsychotic, and medications for insomnia. Conclusions Clinicians responding to the survey reported a range of delirium assessment and management practices in postoperative pediatric cardiac surgery patients. Study results highlight the need for improvement in delirium education for pediatric cardiac intensive care clinicians as well as the need for systematic evaluation of current delirium assessment and management practices.

We sought to evaluate the incidence of Fontan failure or complication and its relation to death in patients having contemporary Fontan strategies over 2 decades.Five hundred patients who underwent Fontan completion (extracardiac, n = 326; lateral tunnel, n = 174) from 1985 to 2012 were reviewed. Patient characteristics, modes of Fontan failure/complication and death, and predictors for Fontan failure/complication and death were analyzed.There were 23 early deaths (4.6%) and 17 late deaths (3.4%), with no early death since 2000. Survival has improved over time (p0.001). Twenty-three of 40 patients who died were identified as Fontan failure before death, including ventricular dysfunction (n = 14), pulmonary vascular dysfunction (n = 4), thromboembolism (n = 2), and arrhythmia (n = 4). Mode of death was circulatory failure (n = 18), multiorgan failure (n = 6), pulmonary failure (n = 3), cerebral/renal (n = 5), and sudden death (n = 4). Modes of failure/complication were directly (65%) or conceivably (10%) related to death in 30 of 40 patients (75%). Forty-eight percent of survivors had late Fontan complication(s). Five-year freedom from late Fontan complication was lower among patients who died compared with patients who survived (29.4% versus 53.3%, p0.001). Ventricular dysfunction (p = 0.001) and higher pulmonary artery pressures (p0.001) after Fontan were predictors for death. Longer cardiopulmonary bypass time (p = 0.032) and reinterventions (p0.001) were predictors for late Fontan complication.Early death in the early era has been overcome. Yet the incidence and causes of late death remain unchanged. There was a strong causative relationship between the mode of Fontan failure/complication and death, indicating the importance of early recognition and treatment of Fontan failure/complication.

Objective Although heart failure (HF) is the leading cause of premature death in adult congenital heart disease (ACHD), little population-specific data exist. This study reports early experience from a dedicated, sub-specialty adult congenital heart disease-heart failure (ACHD-HF) clinic, aiming to identify risk factors for adverse outcome. Methods Between 2012 and 2015, 126 patients (57% male) attended the ACHD-HF clinic. Baseline and follow-up data were analysed and compared across 4 anatomical/physiological subgroups: cyanotic ACHD, Fontan circulation (1V), biventricular circulation with a subaortic right ventricle (2V-RV) and biventricular circulation with a subaortic left ventricle (2V-LV). Predictors of the composite primary outcome: death, transplant or ventricular assist device (VAD) were identified using multivariable Cox proportional hazard models. Results Mean age at first visit was 38±13years. Patients were grouped as follows: cyanotic ACHD 10%, 1V 24%, 2V-RV 29% and 2V-LV 37%. During a median follow-up of 1.7 (IQR 0.8–2.9) years, 38 patients (30%) reached the primary outcome. Event-free survival was 89%, 78% and 63% at 1, 2 and 3years. Forty (31.7%) patients experienced 69 HF hospitalisations. Between-group differences were noted for systolic function, valvular regurgitation, pacing prevalence and invasive hemodynamics. Multivariable analysis revealed 2V-RV subgroup ( p =0.001), NYHA class ( p =0.002) B-type natriuretic peptide >164pg/ml ( p =0.003) and sodium p =0.036) as independently associated with death, transplant or VAD. Conclusions Our young ACHD-HF patients experienced high adverse event rates during a short period of follow-up. The prognostic markers identified will aid clinicians to stratify short-term risk and thereby guide advanced HF management decisions in ACHD.

OBJECTIVES Right ventricular (RV) failure from increased pressure loading is a frequent consequence of acquired and congenital heart diseases. However, the mechanisms involved in their pathophysiology are still unclear, and few data exist on RV pressure-loading models and early versus late effects on RV and left ventricular responses. We characterized a rabbit model of chronic RV pressure overload and early-late effects on biventricular function. METHODS Twenty-one New Zealand white rabbits were randomized into 3 groups: (i) sham, (ii) pulmonary artery (PA) banding (PAB) for 3 weeks (PAB3W) and (iii) PAB for 6 weeks (PAB6W). Progressive RV pressure overload was created by serial band inflation using an adjustable device. Molecular, echocardiographic and haemodynamic studies were performed. RESULTS RV pressure overload was achieved with clinical manifestations of RV failure. Heart and liver weights were significantly higher after PAB. PAB-induced echocardiographic ventricular remodelling increased wall thickness and stress and ventricular dilation. Cardiac output (ml/min) (sham 172.4 ± 42.86 vs PAB3W 103.1 ± 23.14 vs PAB6W 144 ± 60.9, P = 0.0027) and systolic and diastolic functions decreased; with increased RV end-systolic and end-diastolic pressures (mmHg) (sham 1.6 ± 0.66 vs PAB3W 3.9 ± 1.8 vs PAB6W 5.2 ± 2.2, P = 0.0103), despite increased contractility [end-systolic pressure-volume relationship (mmHg/ml), sham 3.76 ± 1.76 vs PAB3W 12.21 ± 3.44 vs PAB6W 19.4 ± 6.88, P

Remote ischemic conditioning (RIC) is at a pivotal point in its evolution, both in terms of its adoption as a therapy and its viability commercially. The most usual way of inducing RIC, with a standard blood pressure cuff and a stopwatch, is time-consuming and potentially inaccurate and unsafe. Development of automated devices have facilitated large-scale randomized trials and will make clinical deployment of the technique more straightforward. Both the medical and commercial future of RIC will depend on the results of upcoming phase 3 pivotal trials.

Background Pulmonary vein stenosis is emerging as an important clinical problem in ex-premature infants. Methods We sought to describe the epidemiology of pulmonary vein stenosis affecting ex-premature infants by a multicenter retrospective cohort study of patients from seven children's hospitals diagnosed between 2000-2014. Results We identified 39 ex-premature patients (26 males, median gestational age 28 weeks range 22-36 weeks, birth weight 1.1 kg range 433-2645–g) with pulmonary vein stenosis. Median age at diagnosis was 6.5 months (1 month-6 years). Presentation with pulmonary hypertension occurred in 26/39 (67%) and 29/39 (74%) had bronchopulmonary dysplasia, 15 (39%) were born of twin pregnancies with unaffected twin siblings. A median of 5 (range 1-25) echocardiograms was performed prior to diagnosis. The diagnosis was made using echocardiography in 22/39 (56%), by multi-detector contrast computed tomography scan (CT) in 8/39 (21%), cardiac catheterization in 6/39 (15%) patients, magnetic resonance imaging in 3/39 (8%). Freedom from death or re-stenosis was 73% at 1-year, 55% at 2, 5, and 10 years. Factors associated with shorter survival or re-stenosis were stenosis of ≥3 pulmonary veins (P

A comprehensive understanding of the normal and abnormal aortic root is paramount if we are to improve not only our assessment of the aortic root and its components but also the surgical approach to reconstructing this complex structure when congenitally malformed. Most anatomic and imaging-based classifications of the normal root recognize and describe the basic components, which include the shape and size of the three aortic sinuses and their three valvar leaflets, as well as the sinutubular junction and proximal ascending aorta. However, the three interposing fibrous interleaflet triangles, which share an intimate relationship with all elements of the root, are often ignored. In consequence, the important role the interleaflet triangles play in determining the function of the normal and congenitally malformed aortic root is underappreciated. Additionally, the subtle asymmetries found in the normal aortic root, such as differences between the sizes of the described components, underlie its hemodynamic efficiency. In this review the authors describe the complex structure of the normal aortic root, contrasting these normal characteristics with those found in the unicuspid and bicuspid variants of congenitally malformed aortic valves. Many of these features are readily recognizable using current imaging modalities and so should become a standard part of the description of aortic valvar disease. The authors believe that this thorough morphologic approach will provide a framework for the re-creation of a more normal aortic root at the time of repair or replacement, thereby improving current outcomes.

Objective: Remote ischemic pre-conditioning (RIPC) is highly cardioprotective in models of ischemia-reperfusion (IR) injury but has not been tested in genetically modified mice. This study was design to test whether RIPC rescues cardiomyopathy induced by knockdown of autophagy-related 5 protein (Atg5). Approach and Results: Atg5 knockdown was induced by feeding tamoxifen diet for two weeks in Atg5 flox/flox Cre +/- (KD) mice which were created by crossing Atg5 flox/flox and heterozygous cardiac-specific Cre recombinase transgenic (Cre +/- ) mice. Atg5 flox/flox Cre -/- mice served as controls (CONT). Cardiac function was evaluated by echocardiography 28 days after tamoxifen induction. Autophagy proteins were determined by Western blot analysis. RIPC was induced by four cycles of five minutes of hind limb ischemia with tourniquet followed by five minutes reperfusion. Tamoxifen feeding knocked down Atg5 to 32% (CONT 0.91 ± 0.09 vs KD 0.29 ± 0.01, p < 0.01, n = 7), leading to 96% decrease of autophagy activity indicated by LC3-II/LC3-I ratio (CONT 0.96 ± 0.07 vs 0.06 ± 0.03, p < 0.01, n = 7). This was associated with significant cardiac dysfunction (LV ejection fraction, CONT 59.78% ± 3.26 vs KD 47.13% ± 2.50, n = 8 and 10, p < 0.01) and increased heart weight to body weight ratio (CONT 0.50 ± 0.02 vs KD 0.57 ± 0.01, n = 8 and 10, p < 0.01). RIPC increased levels of Atg5 in Atg5 KD mice by 183% (Sham 1.00 ± 0.16 vs RIPC 1.83 ± 0.14, p < 0.01, n = 11 and 13), leading to 148% increase of autophagy activity (Sham 0.99 ± 0.13 vs RIPC 1.47 ± 0.18, p < 0.05, n = 6 and 7), and resulted in rescued cardiac function in terms of heart weight (CONT 0.50 ± 0.01 vs KD 0.53 ± 0.10, n = 11 and 13 ) and LV ejection fraction (CONT 55.64% ± 2.45 vs 52.48% ±1.61, n = 11 and 13). RIPC also suppressed mTOR phosphorylation by 62% compared with sham procedure in Atg5 KD mice (Sham 1.00 ± 0.18 vs RIPC 0.45 ± 0.08 p < 0.01 n = 11 and 13) which was increased by 650% in Atg5 KD compared with CONT mice (CONT 1.23 ± 0.14 vs KD 6.35 ± 0.09, p < 0.01, n = 7). Conclusion: We conclude that RIPC rescues Atg5 knockdown-induced cardiomyopathy. Our data adds to the emerging data suggesting benefits of RIPC beyond acute cardioprotection in IR injury.

Objective: It has been suggested that miR-144 is pro-atherosclerotic via effects on reverse cholesterol transportation targeting the ATP binding cassette protein 1 (ABCA1). 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 KO mice receiving a high fat diet (HFD). Approach and Results: To identify affected secretory proteins, miR-144 treated endothelial cell culture medium was subjected to proteomic analysis including two-dimensional gel separation 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 KO mice by HFD 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, HFD induced extensive atherosclerosis in miR-144 KO mice in aortic root (WT 100% ± 22.71 vs miR-144 KO 256.88% ± 58.19, p < 0.05, n = 10) and arch areas (WT 100% ± 29.67 vs miR-144 KO 371.74% ± 73.48, p < 0.01, n = 10), and was accompanied by severe fatty liver disease compared with wild type littermates (WT). Vimentin levels were reduced by miR-144 and increased by antagomiR-144 in cultured cardiac endothelial cells without affecting vimentin mRNA levels. Compared with WT, ablation of the miR-144/451 cluster significantly increased plasma vimentin, while vimentin levels were decreased in control mice injected with synthetic miR-144 as double confirmed with Western blot and ELISA assays. Furthermore, increased vimentin expression was seen in the commissural regions of the aortic root (WT 100% ± 10.02 vs 164.19 ± 13.90, p < 0.01, n = 10) and collocated with other areas of aortic atherosclerosis. In contrast, neither liver ABCA1 nor circulating cholesterol levels were different between WT and miR-144/451 KO mice. Conclusion: We conclude that miR-144 is a potential regulator of the development of atherosclerosis via changes in vimentin signaling and both miR-144 and vimentin are potential therapeutic targets for atherosclerosis.

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 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.

BackgroundIn recent Danish nationwide register-based study, adults with small, unrepaired atrial septal defects (ASD) have increased risk of pneumonia, atrial fibrillation (AF) and stroke. Moreover, they revealed higher mortality than the background population.ObjectiveIn this nationwide study, we evaluate the hidden burden of atrial and ventricular arrhythmias in adult patients with a small, unrepaired ASD without a previous diagnosis of AF.MethodsAll Danish patients, aged 18–65, diagnosed between 1953 and 2011 with an unrepaired ASD and no documented AF were invited for 7 days Holter-recording, echocardiography and 6 min walk test. The first 48 hours Holter-recording was completely analysed, while only AF was screened for throughout all 7 days. Furthermore, the entire patient group were characterised using the unique Danish registries.ResultsA total of 151 patients (mean age 32 years) were included. Approximately 80% of the patients had spontaneous closure of their defect. Despite this, occult arrhythmias were frequent. The most common arrhythmia was supraventricular tachycardia (n=24, 16%) with non-sustained atrial arrhythmias in 21 patients and AF in two patients. A considerable number of patients had non-sustained ventricular tachycardia (n=12, 8%). Patients with ASD and tachyarrhythmias had increased right ventricular to left ventricular diastolic area in echocardiography and higher age when compared with ASD patients without arrhythmias.ConclusionAdult patients with small, unrepaired ASD have a hidden burden of both atrial and ventricular tachyarrhythmias. The mechanism likely relates to the residua of previous right-heart volume overload and incomplete reverse remodelling. Our results support guidelines recommending continued follow-up of patients with small, unrepaired ASD.

Remote ischemic conditioning (RIC) is acutely cardioprotective in ischemia-reperfusion injury. We aimed to evaluate the effect of RIC on septic cardiomyopathy and associated multi-organ failure in a lipopolysaccharide (LPS)-induced sepsis mouse model. Balb/c mice were divided into sham, LPS, and LPS + RIC groups. LPS 10 mg/kg or saline control was injected intraperitoneally. RIC was performed by four cycles of 5 min ischemia and 5 min reperfusion of the left lower limb just before the LPS injection. Cardiac function on echocardiography, circulating mediators, blood biochemistry, and MAPK signalling was assessed. Survival 7 days after LPS injection was evaluated in sham-treated, RIC, and daily repeated RIC groups. An LPS-induced decrease in cardiac output was ameliorated by RIC with preserved left ventricular systolic function. LPS-induced increases in TNF-α, IL-1β, IL-6, and high-mobility group box 1 protein (HMGB1) were significantly suppressed by RIC. RIC also suppressed increases in plasma cardiac troponin I, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine with suppressed ERK and JNK phosphorylation in heart, liver, and kidney tissue. RIC significantly improved survival rate (p = 0.0037). Survival rate in the daily repeated RIC group was 100%, and it was higher than that in the RIC group (p = 0.0088). In summary, RIC reduced circulating and myocardial inflammatory mediators associated with septic cardiomyopathy, and led to improved ventricular function, cardiac output, and survival. Our data also revealed that chronic RIC has additional benefit in terms of mortality in sepsis. While further studies are required, RIC may be a clinically useful tool to ameliorate sepsis-induced cardiomyopathy.

The population of adults with congenital heart disease (CHD) has increased dramatically over the past few decades, with the number of adults with CHD now surpassing the pediatric population. Adult CHD (ACHD) encompasses a broad range of presentations, with some patients diagnosed for the first time in adulthood. The majority of patients however have undergone a palliative repair during childhood and now are dealing with sequela and/or residual disease years to decades later. All of which may be compounded by acquired cardiovascular disease. In this review, we describe the physiologic underpinnings of the interaction between the respiratory and cardiovascular systems and their clinical impact in ACHD. We will review the physiologic underpinnings of cardiopulmonary interactions and the effects of respiration on cardiovascular function, the impact of respiration on cardiovascular function in adult patients with congenital and acquired heart disease, the effects of respiratory disease on cardiovascular function, and the impact of cardiovascular disease on respiratory function.

BACKGROUND: Ventricular septal defects (VSDs) generally have benign long-term prognoses, but recent studies have indicated increased pulmonary vascular resistance. A potential tool for monitoring pulmonary artery pressure is heart rate variability, and therefore, the aim of this study was to assess heart rate variability in adults with a surgically repaired or unrepaired VSD.METHODS: In a long-term, follow-up study, three groups were included; VSD-patients operated in early childhood, patients with an open VSD, and controls. For each patient, 24-hour Holter monitoring was performed and heart rate variability was assessed.RESULTS: In total, 30 participants with a surgically closed VSD, 30 participants with an unrepaired VSD, and 36 controls were included. In the closed VSD group, there was a higher proportion of participants, who had low sNN50 (p = 0.005) and low sNN6% (p = 0.017) than in the other two groups. Similar differences were found when sNN50 was divided into increases and decreases (p = 0.007 and p = 0.005, respectively) as well as sNN6% (p = 0.014 and p = 0.014, respectively). Lastly, there was a higher proportion of patients in the closed VSD group with low rMSSD than in the other two groups (p = 0.005). For the closed VSD group, the proportion of participants with low total sNN50 (p = 0.046) and low total sNN6% (p = 0.046) were higher among participants with a complete right bundle branch block (RBBB) than among participants with no or an incomplete RBBB.CONCLUSIONS: Adults who had surgical VSD closure in early childhood had impaired heart rate variability and, particularly, participants with complete RBBB had lower heart rate variability.

BACKGROUND: Adult patients with small, unrepaired atrial septal defects (ASD) have higher late mortality than the background population. In this nationwide study, we characterize the late natural history of adults with small, unrepaired ASD.METHODS: Using the Danish National Patient Registry, we included all Danish patients, diagnosed between 1953 and 2011 with an unrepaired ASD. Additionally, all patients, aged 18-65, were invited for clinical testing. Patients also completed a general health survey for comparison with the general population.RESULTS: We identified 723 patients with a small unrepaired ASD. Since the time of diagnosis, 182 patients had died, with an average lifespan of 63 years. The most common cause of death was heart failure. Furthermore, ASD patients had a higher burden of chronic disease than the general population (38.2% vs. 26.9%; p = 0.005), particularly lung disease (3.6% vs. 0.9%; p = 0.008). A total of 153 patients (mean age 32 y) underwent additional testing. On echocardiography an open defect was verified in 19.6% (n = 30) of the patients, of which half subsequently underwent intervention. Interestingly, 6-minute walking distance was markedly reduced (p CONCLUSIONS: Patients with small, unrepaired ASD in adult life have reduced lifespan, more chronic diseases, impaired submaximal exercise capacity, and higher levels of stress than the general population. The current guidelines for intervention and follow-up may need to be reconsidered.

We have previously shown that MicroRNA (miR) -144 is a key modulator of the acute cardioprotection associated with remote ischemic preconditioning and post myocardial infarction (MI) remodeling. In this study we examine the biology of the remodeling response after permanent ligation of the left anterior descending coronary artery in male miR-144 KO mice, and wild-type littermates (WT). Collagen content and cross linking were determined by hydroxyproline and pyridinoline assays, MI size and scar thickness were measured post PicoSirius Red staining, and cardiac function was evaluated by echocardiography. miR-144 KO mice developed normally with normal cardiac function, however after MI, infarction size was greater and scar thickness was reduced in miR-144 KO mice compared with WT littermates. miR-144 KO mice had a lower incidence of acute cardiac rupture compared with WT littermates early after MI but there was impaired late remodeling, reflected by increased total cardiac collagen content and collagen cross-linkage associated with changes in Zeb1/LOX1 axis, and decreased left ventricular ejection fraction. We conclude that miR-144 is involved in extracellular matrix remodeling post MI and its loss leads to increased myocardial fibrosis and impaired functional recovery.

Background: miR-144 has potential benefits in protecting against myocardial ischemia and suppression of tumor growth. We have previously shown that a single intravenous injection of miR-144 provides potent cardioprotection, but its kinetics and distribution are not known. Methods: Single stranded mature miR-144 or Cy3-labelled-miR-144 was delivered into C57/B6 mice by tail vein injection. Results: After intravenous injection, the signal of Cy3-labelled-miR-144 in the kidney, brain, heart and liver peaks at 60 minutes, and is predominantly localised to the endothelium at that stage. In the kidney and heart, Cy3-labelled-miR-144 signal is detectable within the parenchymal tissues for at least 3 days, after which it starts to decrease, but brain Cy3-miR-144 signal rapidly decreases after 1 hour, and is lost at day 1, with no parenchymal uptake detected. Cy3-miR-144 signal can be detected until day 28 in the liver. Stem loop RTPCR confirmed the temporal pattern shown by miR-144 in kidney, brain and heart, but in liver there was a continuous rise following the initial injection until day 28 with no signs of decrease, suggesting de-novo synthesis. Conclusion: There is early endothelial uptake of injected miR-144 followed by organ-specific distribution and kinetics. In the liver, there appears to be a positive feedback process that leads to continued accumulation of miR-144 that persists for at least 28 days. These observations should be taken into account when designing experiments utilizing parenteral miR-144 and assessing the biology of its actions.

The purpose of this review is to discuss current outcomes for patients with adult congenital heart disease, assess the level of knowledge regarding the impact of comorbidities, and discuss the various models of care with a view to establish the optimal environment for the care of these patients in the future.MEDLINE and PubMed.There is an increasingly large population of adults with previously operated congenital heart disease. Consequently, there are increasing numbers of adults requiring intensive care support after re-do surgery, or as a consequence of medical complications of their underlying cardiac disease. There is relatively little data specific to this population to guide optimal disposition and care models.