ACTION-ARC Pediatric and Adult Congenital Heart Disease Ventricular Assist Device Adverse Event Definitions-2023.

Adverse events (AEs) experienced by children and adults with congenital heart disease (CHD) on ventricular assist devices (VADs) are sometimes unique to these populations. The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) and the Academic Research Consortium (ARC) aimed to harmonize definitions of pediatric and CHD AEs for use in clinical trials, registries, and regulatory evaluation. Data from the ACTION registry and adjudication committee were used to adapt general mechanical circulatory support ARC definitions. This ACTION-ARC international expert panel of trialists, clinicians, patients, families, statisticians, biomedical engineers, device developers, and regulatory agencies drafted and iterated definitions harmonized to ACTION data and existing literature during sessions conducted between December 2022 and May 2023, followed by dissemination across clinical/research audiences and professional organizations and further revision. Both email-linked, internet-based surveys and in-person discussions were used as a modified Delphi process. Nineteen AE types were identified and defined, including seven new event types and six event types that were deleted and will no longer be collected, achieving consensus. ACTION-ARC paired rigorous development with methodical stakeholder involvement and dissemination to define pediatric VAD AEs to facilitate assimilation of data across future clinical trials and evaluation of devices for VAD-supported children and adults with CHD.

Hydrazone-Linked Covalent Organic Framework Catalyst via Efficient Pd Recovery from Wastewater.

Global consumption and discharge of palladium (Pd) have raised environmental concerns but also present an opportunity for the sustainable recovery and reuse of this precious metal. Adsorption has proven to be an efficient method for the selective recovery of Pd from industrial wastewater. This study investigated a hydrazone-linked covalent organic framework (Tfpa-Od COF) as a potential material for the high-affinity adsorption of Pd2+ ions from wastewater, achieving a Kd value of 3.62 × 106 mL g-1. The electron-rich backbone of the COF contributes to its excellent selective removal efficiency (up to 100%) and adsorption capacity of 372.59 mg g-1. Furthermore, the Pd-adsorbed COF was evaluated as a sustainable catalyst for the Suzuki-Miyaura coupling reaction, demonstrating good catalytic conversion and recyclability. This work attempts to showcase a protocol for reusing waste palladium generated in water to fabricate heterogeneous catalysts and, thereby, promote the circular economy concept.

Prolonged Inotrope Use After Surgery for Congenital Heart Disease: A Common Occurrence with a High Burden of Mortality.

Outcomes in patients requiring prolonged inotropes (PI) following surgery for congenital heart disease (CHD) have not been well studied. We aimed to describe the burden of PI use in the immediate postoperative period after CHD surgery and identify risk factors for in-hospital mortality. We conducted a retrospective cohort study using the Pediatric Health Information System® (PHIS) database. Patients 0-18 years with CHD who underwent cardiovascular surgery from 2010 to 2020 were included. Patients who received inotropic medications for > 7 consecutive days after surgery were in the PI group and all others in the control group. Patients who died before 7 days were excluded. Multivariable mixed-effect logistic regression was used to examine risk factors for in-hospital mortality. There were 110,271 patients from 48 centers included, 10,292 in the PI group and 99,979 in the control group. In-hospital mortality was significantly higher in the PI group (24.9% vs. 4.6%, p < 0.001). Ventricular assist device use was rare (1.6%). After adjustment, odds of in-hospital mortality in the PI group was 3.5 (95% CI 3.3-3.8) times higher than in controls. Independent risk factors for in-hospital mortality were age, non-White race, class of CHD, number of complex chronic conditions, preoperative inotrope, preoperative extracorporeal membrane oxygenation, sepsis, stroke, renal failure, number of inotropes at 7 days, and discharge year (p < 0.01 for all). Postoperative PI use in CHD is common and carries a considerable burden of mortality. Additional work is needed to understand which risk factors are modifiable and which patients may benefit from reintervention or advanced heart failure therapies.

Development and Validation of a Novel Pediatric Mechanical Circulatory Support Risk Stratification Tool: The Advanced Cardiac Therapies Improving Outcomes Network (ACTION) Ventricular Assist Device Score.

We sought to develop and validate a new risk stratification score for mortality for children supported with a ventricular assist device (VAD). This retrospective, multicenter study used data from patients undergoing VAD implantation between April 2018 and February 2023 at 44 participating institutions in the Advanced Cardiac Therapies Improving Outcomes (ACTION) network. Multivariable Cox proportional-hazards modeled mortality after VAD implantation. A total of 1,022 patients were enrolled. The 1 year mortality was 19% (95% confidence interval [CI]: 16-23). The multivariable model was used to build the ACTION VADs risk stratification score with four components: ventilation, advanced organ support (dialysis or ECMO), diagnosis, and size (weight ≤5 kg). One point is added for each risk factor. Based on the sum of the risk factors, patients were classified into four classes: class 0-green (4% mortality at 1 year), class 1-yellow (16% mortality at 1 year), class 2-orange (21% mortality at 1 year), and class 3 or higher-red (42% mortality at 1 year). The score performed well, with area under the curve (AUC) of 0.72 and excellent calibration. The ACTION VADs score for mortality can be calculated easily and offers risk stratification and prognostic information for pediatric VAD candidates. This is the first validated risk assessment tool for pediatric mechanical circulatory support.

Mechanical Circulatory Support in Pediatric Myocarditis: Support Strategies and Outcomes in a Nationally Representative Cohort.

Background: Myocarditis is a common cause of pediatric heart failure which may require mechanical circulatory support (MCS). The purpose of this study is to describe MCS strategies used in a nationwide cohort of pediatric patients with myocarditis, identify trends over time, and compare outcomes between MCS strategies. Methods: This study utilized the Kids' Inpatient Database (KID), a national sample of administrative discharge data. KID admissions from 2003-2016 were queried using ICD-9/10 codes to identify those with a diagnosis of myocarditis. MCS outcomes were compared using logistic regression. Results: Of 5,661 admissions for myocarditis, MCS was used in 424 (7.5%), comprised of extracorporeal membrane oxygenation (ECMO) in 312 (73.6%), including 32 (10.2%) instances of extracorporeal cardiopulmonary resuscitation (ECPR), temporary ventricular assist devices (tVAD) in 28 (6.6%), durable VAD (dVAD) in 42 (9.9%) and combination MCS in 42 (9.9%). MCS use increased over time (p=0.031), but MCS strategies did not significantly change. Mortality was high in the MCS group (28.3%). There was no difference in odds of death in the VAD only or combination MCS group compared to the non-ECPR ECMO group (p=0.07 and p=0.65, respectively). Conclusion: MCS is used in 1 in 13 pediatric myocarditis cases, and MCS use is increasing over time with ECMO remaining the most frequently used modality. Mortality remains high in patients that receive MCS but does not differ between those receiving VAD or combination MCS as compared to non-ECPR ECMO on unadjusted analysis. Further prospective analysis is required to evaluate the relative effectiveness of MCS modalities in this disease.

Hybrid stage 1 palliation with simultaneous off-pump ventricular assist device placement in neonates with high-risk single ventricle anatomy: Initial experience.

Background: Infants with single ventricle heart disease and severe atrioventricular valve regurgitation have poor outcomes following conventional staged palliation. As such, ventricular assist device (VAD) placement along with hybrid stage 1 palliation has been proposed as a bridge to heart transplant. We present a novel surgical technique for VAD implantation concurrent with hybrid stage 1 that avoids cardiopulmonary bypass. Methods: We performed a retrospective review of our institutional experience with this novel surgical technique. Results: Three patients (weight, 2.7-3.5 kg; age, 3 to 5 days) underwent hybrid stage 1 with VAD placement, consisting of bilateral 3.5-mm expandable polytetrafluoroethylene (PTFE) pulmonary artery bands, a ductal stent, a 6-mm Berlin Heart outflow cannula onto the main pulmonary trunk with a 10-mm graft, a 6-mm Berlin Heart outflow cannula onto the right atrium, and a 10-mL Berlin Heart pump. In patients with severe aortic arch hypoplasia or coarctation, a 4-mm PTFE graft was sewn from the VAD outflow graft to the innominate artery to protect coronary and cerebral perfusion. Procedures were performed off bypass with minimal blood product use. Patients were extubated on postoperative days 2, 2, and 5. There were no procedural complications. All patients were transferred out of the intensive care unit and demonstrated appropriate weight gain. Anticoagulation strategy was bivalirudin and antiplatelet therapy. The patients underwent transplantation after 149 days, 157 days, and 288 days of support. Conclusions: Off-pump single ventricle VAD placement is technically feasible and can be done at the time of hybrid stage 1 palliation with minimal operative morbidity as a bridge to transplant.

Survival does not differ by annual center transplant volume-A Pediatric Heart Transplant Society Registry study.

BACKGROUND: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high-risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. METHODS: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan-Meier analysis. RESULTS: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p = .75), in patients with CHD (p = .79) or in patients with cardiomyopathy (p = .23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p = .17, p = .31, and p = .10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p < .0001), though no discernible pattern related to high or low center volume. CONCLUSIONS: Outcomes are similar among transplant centers of all sizes, including for high-risk patient groups with CHD. Future work is needed to understand how patient-specific risk factors may vary among centers of various sizes and whether this influences patient outcomes.

Emergency Department Use and Hospital Mortality Among Heart Transplant Recipients in the United States.

BACKGROUND: Annual heart transplant (HT) volumes have increased, as have post-HT outpatient care needs. Data on HT-related emergency department (ED) visits are limited. METHODS AND RESULTS: A retrospective analysis of 177 450 HT patient ED visits from the 2009 to 2018 Nationwide Emergency Department Sample was conducted. HT recipients, primary diagnoses, and comorbidities associated with ED visits were identified via International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. Multivariable logistic regression was used to predict outcomes of hospital admission and death. HT volumes and HT-related ED visits increased from 2009 to 2018. Infection was the most common primary diagnosis (24%), and cardiac primary diagnoses represented 10% of encounters. Hospital admissions occurred in 48% of visits, but overall mortality was low (1.6%). Length of stay was 3.1 days (interquartile range, 1.6-5.9 days), and comorbidity burden was high: 42% had hypertension, 38% had diabetes, and 31% had ≥2 comorbidities. Those aged ≥65 years had significantly higher odds of admission (odds ratio [OR], 2.14 [95% CI, 1.97-2.33]) and death (OR, 2.06 [95% CI, 1.61-2.62]). Comorbidities increased odds of admission (OR, 1.62 [95% CI, 1.51-1.75]) but not death. Renal primary diagnosis had the highest risk of admission (OR, 4.1 [95% CI, 3.6-4.6]), but cardiac primary diagnosis had the highest odds of death (OR, 11.6 [95% CI, 9.1-14.8]). CONCLUSIONS: HT-related ED visits increased from 2009 to 2018 with high admission rates but low in-hospital mortality, suggesting an opportunity to improve prehospital care. Older patients and those with cardiac primary diagnoses had the highest risk of death. The observed contrast between predictors of admission and mortality signals a need for further study to improve risk stratification and outpatient care strategies.

Date fruit melanin is primarily based on (-)-epicatechin proanthocyanidin oligomers.

Plant-based melanin seems to be abundant, but it did not receive scientific attention despite its importance in plant biology and medicinal applications, e.g. photoprotection, radical scavenging, antimicrobial properties, etc. Date fruit melanin (DM) has complex, graphene-like, polymeric structure that needs characterization to understand its molecular properties and potential applications. This study provides the first investigation of the possible molecular composition of DM. High performance size-exclusion chromatography (HPSEC) suggested that DM contains oligomeric structures (569-3236 Da) and transmission electron microscopy (TEM) showed agglomeration of these structures in granules of low total porosity (10-1000 Å). Nuclear magnetic resonance (NMR) spectroscopy provided evidence for the presence of oligomeric proanthocyanidins and electron paramagnetic resonance (EPR) spectroscopy revealed a g-factor in the range 2.0034-2.005. Density functional theory (DFT) calculations suggested that the EPR signals can be associated with oligomeric proanthocyanidin structures having 4 and above molecular units of (-)-epicatechin. The discovery of edible melanin in date fruits and its characterization are expected to open a new area of research on its significance to nutritional and sensory characteristics of plant-based foods.

Hypertension: An Important But Reversible Cause of Systolic Dysfunction in a Cohort of Pediatric Patients.

Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. We aimed to describe the presentation and outcomes of pediatric CDHTN and identify clinical features associated with resolution of dysfunction. A single-center retrospective cohort study of patients ≤ 21 years with CDHTN from January 2005-September 2020 was performed. Patients with systolic dysfunction without another cause, blood pressure > 95th percentile, and physician judgment that dysfunction was secondary to hypertension were included. Demographics, clinical characteristics, echocardiographic findings, and outcomes were examined using Fisher's exact and Mann-Whitney U tests. Multiple correspondence analysis was used to explore the relationship of resolution of dysfunction to clinical features. Thirty-four patients were analyzed at a median age of 10.9 (IQR 0.3-16.9) years. Patients were divided into groups < 1 year (n = 12) and ≥ 1 year (n = 22). Causes of hypertension were varied by age, with renovascular disease most common in infants (42%) and medical renal disease most common in older patients (77%). Echocardiography demonstrated mild LV dilation (median LV end-diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.4). Most patients (81%) had resolution of dysfunction, particularly infants (92%). One patient died and one patient was listed for heart transplant. None required mechanical circulatory support (MCS). No clinical features were statistically associated with resolution of dysfunction. Hypertension is an important but reversible cause of systolic dysfunction in children. Patients are likely to recover with low mortality and low utilization of MCS or transplantation. Further studies are needed to confirm features associated with resolution of dysfunction.

Outcomes after initial heart failure consultation in Fontan patients.

BACKGROUND: Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care. METHODS: This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as "too late" (death or declined for transplant due to being too sick) and/or "care escalation" (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. "Late referral" was defined as those referred too late and/or had care escalation. RESULTS: Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8-21.5, p=0.004). CONCLUSIONS: Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

Impact of Ventricular Dysfunction and Atrioventricular Valve Regurgitation on Pre-Fontan Attrition.

BACKGROUND: There is a significant incidence of pre-Fontan attrition-defined as failure to undergo Fontan completion-after superior cavopulmonary connection. This study investigated the impact of at least moderate ventricular dysfunction (VD) and atrioventricular valve regurgitation (AVVR) on pre-Fontan attrition. METHODS: This single-center retrospective cohort study included all infants who underwent Norwood palliation from 2008 to 2020 and subsequently underwent superior cavopulmonary connection. Pre-Fontan attrition was defined as death, listing for heart transplantation before Fontan completion, or unsuitability for Fontan completion. The study's secondary outcome was transplant-free survival. RESULTS: Pre-Fontan attrition occurred in 34 of 267 patients (12.7%). Isolated VD was not associated with attrition. However, patients with isolated AVVR had 5 times the odds of attrition (odds ratio, 5.4; 95% CI 1.8-16.2), and patients with both VD and AVVR had 20 times the odds of attrition (odds ratio, 20.1; 95% CI 7.7-52.8) compared with patients without VD or AVVR. Only patients with both VD and AVVR had significantly worse transplant-free survival compared with patients without VD or AVVR (hazard ratio, 7.7; 95% CI 2.8-21.6). CONCLUSIONS: The additive effect of VD and AVVR is a powerful contributor to pre-Fontan attrition. Future research investigating therapies that can mitigate the degree of AVVR may help improve Fontan completion rates and long-term outcomes.

Expanding use of the HeartMate 3 ventricular assist device in pediatric and adult patients within the Advanced Cardiac Therapies Improving Outcomes Network (ACTION).

BACKGROUND: We report current outcomes in patients supported with the HeartMate 3 (HM3) ventricular assist device in a multicenter learning network. METHODS: The Advanced Cardiac Therapies Improving Outcomes Network database was queried for HM3 implants between 12/2017 and 5/2022. Clinical characteristics, postimplant course, and adverse events were collected. Patients were stratified according to body surface area (BSA) (<1.4 m2, 1.4-1.8 m2, and >1.8 m2) at device implantation. RESULTS: During the study period, 170 patients were implanted with the HM3 at participating network centers, with median age 15.3years; 27.1% were female. Median BSA was 1.68 m2; the smallest patient was 0.73 m2 (17.7 kg). Most (71.8%) had a diagnosis of dilated cardiomyopathy. With a median support time of 102.5days, 61.2% underwent transplantation, 22.9% remained supported on device, 7.6% died, and 2.4% underwent device explantation for recovery; the remainder had transferred to another institution or transitioned to a different device type. The most common adverse events included major bleeding (20.8%) and driveline infection (12.9%); ischemic and hemorrhagic stroke were encountered in 6.5% and 1.2% of patients, respectively. Patients with BSA <1.4 m2 had a higher incidence of infection, renal dysfunction, and ischemic stroke. CONCLUSIONS: In this updated cohort of predominantly pediatric patients supported with the HM3 ventricular assist device, outcomes are excellent with <8% mortality on device. Device-related adverse events including stroke, infection, and renal dysfunction were more commonly seen in smaller patients, highlighting opportunities for improvements in care.

Taking ACTION: A Prognostic Tool for Pediatric Ventricular Assist Device Mortality.

We sought to develop a contemporary risk assessment tool for use in pediatric ventricular assist device (VAD) candidates to estimate risk for mortality on the device using readily available preimplantation clinical data. Training and testing datasets were created from Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry data on patients supported with a VAD from 2012 to 2021. Potential risk factors for mortality were assessed and incorporated into a simplified risk prediction model utilizing an open-source, gradient-boosted decision tree machine learning library, known as random forest. Predictive performance was assessed by the area under the receiver operating characteristic curve in the testing dataset. Nine significant risk factors were included in the final predictive model which demonstrated excellent discrimination with an area under the curve of 0.95. In addition to providing a framework for establishing pediatric-specific risk profiles, our model can help inform team expectations, guide optimal patient selection, and ultimately improve patient outcomes.

Reduced incidence of cardiac rejection in multi-organ transplants: A propensity matched study.

BACKGROUND: Rejection remains a primary cause of graft loss after heart transplant (HT). Recognizing the immunomodulation of multi-organ transplant can enhance our understanding of the mechanisms of cardiac rejection. METHODS: This retrospective cohort study identified patients from the UNOS database with isolated heart (H, N = 37 433), heart-kidney (HKi, N = 1516), heart-liver (HLi, N = 286), and heart-lung (HLu, N = 408) transplants from 2004 to 2019. Propensity score matching reduced baseline differences between groups. Outcomes included risk of rejection prior to transplant hospital discharge and within 1 year, and mortality within 1 year of transplant. RESULTS: In the propensity score matched data, the relative risk of being treated for rejection prior to transplant hospital discharge was 61% lower for HKi (RR .39, 95% CI .29, .53) and 87% lower for HLi (RR .13, 95% CI .05, .37) compared to H. Similarly, the probability of being treated for rejection in the first year after transplant remained lower in HKi (RR .45, 95% CI .35, .57) and HLi (RR .13, 95% CI .06, .28) compared to H. The 1-year survival analysis revealed an equivalent risk of death in HKi (HR .84, 95% CI .68, 1.03) and HLi (HR 1.41, 95% CI .83, 2.41) compared to H, while HLu had a higher risk of death in the first year after transplant (HR 1.65, 95% CI 1.17, 2.33). CONCLUSIONS: Recipients of HKi and HLi experience a reduced risk of rejection when compared to H, but an equivalent risk of 1 yr mortality. These findings have important implications for the future of HT medicine.

Impact of Weight on Ventricular Assist Device Outcomes in Dilated Cardiomyopathy Patients in Pediatric Centers: An ACTION Registry Study.

Ventricular assist device (VAD) options vary for children in different weight groups. This study evaluates contemporary device usage and outcomes for children based on weight. Data from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry were examined for patients with dilated cardiomyopathy (DCM) in 4 weight cohorts: <8 kg, 8-20 kg, 21-40 kg, and >40 kg, for devices implanted 3/2013-10/2020. Adverse event rates and ultimate outcome (deceased, alive on device, transplanted, or ventricular recovery) were analyzed. 222 DCM patients were identified with 24% in cohort 1, 23% in cohort 2, 15% in cohort 3, and 38% in cohort 4. Of 272 total implants, paracorporeal pulsatile devices were most common (95%) in cohorts 1 and 2 and intracorporeal continuous devices (81%) in cohorts 3 and 4. Stroke was noted in 17%, 12%, 6%, and 4% of cohorts, respectively (Cohort 1 vs. 4 and 2 vs. 4 - p = 0.01; other comparisons - not significant). Incidences of major bleeding, device malfunction, and infection was not different. All cohorts had >90% positive outcomes. Stroke incidence was higher in smaller cohorts, but other outcomes were similar. Positive outcomes were attained in over 90% across all weight groups, demonstrating excellent outcomes using current VADs in this DCM population.