Predicting Stroke for Pediatric Patients Supported With Ventricular Assist Devices: A Pedimacs Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) provides detailed understanding on pediatric patients supported with ventricular assist devices (VADs). We sought to identify important variables affecting the incidence of stroke in pediatric VADs. METHODS: Between 2012 and 2022, 1463 devices in 1219 patients were reported to Pedimacs from 40 centers in patients aged <19 years at their first VAD implantation. Multiphase parametric hazard modeling was used to identify risk factors for stroke among all device types. RESULTS: Of the 1219 patients, the most common devices were implantable continuous (472 [39%]), followed by paracorporeal pulsatile (342 [28%]), and paracorporeal continuous (327 [27%]). Overall freedom from stroke at 6 months was higher in the recent era (2012-2016; 80.2% [95% CI, 77.1%-82.9%] vs 2017-2023; 87.9% [95% CI, 86.2%-89.4%], P = .009). Implantable continuous VADs had the highest freedom from stroke at 3 months (92.7%; 95% CI, 91.1%-93.9%) and 6 months (91.1%; 95% CI, 89.3%-92.6%), followed by paracorporeal pulsatile (87.0% [95% CI, 84.8%-88.9%] and 82.8% [95% CI, 79.8%-85.5%], respectively), and paracorporeal continuous (76.0% [95% CI, 71.8%-79.5%] and 69.5% [95% CI, 63.4%-74.8%], respectively) VADs. Parametric modeling identified risk factors for stoke early after implant and later. Overall, and particularly for paracorporeal pulsatile devices, early stroke risk has decreased in the most recent era (hazard ratio, 5.01). Among implantable continuous devices, cardiogenic shock was the major risk factor. For patients <10 kg, early hazard was only seen in the previous era. For congenital patients, early hazard was seen in nonimplantable device use and use of extracorporeal membrane oxygenation. CONCLUSIONS: The overall stroke rate has decreased from 20% to 15% at 6 months, with particular improvement among paracorporeal pulsatile devices. Risk factor analyses offer insights for identification of higher stroke risk subsets and further management refinements.

Seventh Annual Society of Thoracic Surgeons Pedimacs Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2022, 1463 devices in 1219 patients aged <19 years were reported to the registry from 40 North American hospitals. RESULTS: Cardiomyopathy remains the most common underlying etiology (59%), followed by congenital heart disease (26%) and myocarditis (8%). Implantable continuous devices were most common (39%) type, followed by paracorporeal pulsatile (28%) and paracorporeal continuous (27%) devices. At 6 months after VAD implantation, a favorable outcome (transplant, recovery, or alive on device) was achieved in 85% of patients, which was greatest among those on implantable continuous VADs (92%) and least for paracorporeal continuous VADs (68%), although the patient population supported on these devices is different. CONCLUSIONS: This Seventh Pedimacs Report demonstrates the continued importance of VADs in the treatment of children. With the complexity of cardiac physiologies and sizes of patients, multiple types of devices are used, including paracorporeal continuous, paracorporeal pulsatile, and implantable continuous devices. The preoperative risk factors and differences in patient populations may account for some of the differences in survival observed among these devices. This report, along with other collaborative work, continues to advance the care of this challenging and vulnerable population.

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.

Survival in Pediatric Patients With Ventricular Assist Devices: A Special Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) provides detailed understanding on pediatric patients supported with ventricular assist devices (VADs). We sought to identify important variables affecting mortality in pediatric VADs. METHODS: Patients aged <19 years, from 2012 to 2021, were included. Survival analyses were performed using Kaplan-Meier. Parametric hazard modeling was used to identify risk factors for death. RESULTS: Of the 1109 patients, the most common devices were implantable continuous (IC, 448 [40%]), followed by paracorporeal pulsatile (PP, 306 [28%]), paracorporeal continuous (PC, 293 [26%]), and percutaneous (58 [5%]). Patients with percutaneous device, infants, congenital heart disease, biventricular support, and Interagency Registry for Mechanically Assisted Circulatory Support profile 1 had worse overall survival at 6 months. Positive outcome was 83% at 6 months. Consistent with their cohort composition, device type positive outcomes at 6 months were IC, 92%; PP, 84%; and PC, 69%. Parametric hazard modeling for overall survival showed an early hazard for death with biventricular support, congenital heart disease (CHD), intubation before implantation, PC device, and renal impairment, whereas a constant hazard was associated with ascites. For patients <10 kg, parametric modeling showed an early hazard for CHD, intubation, and renal impairment. Modeling in CHD patients showed an early hazard for biventricular support, renal impairment, and use of PC/PP devices. CONCLUSIONS: This multivariable analysis of the complete Pedimacs database demonstrates that illness at VAD implantation, diagnosis, and strategy of support affect survival and differ by device type. We hope this is the first step in creating a predictive tool to help providers and families have informed expectations.

Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Key Strategies for Optimizing Pediatric Perioperative Nutrition-Insight from a Multidisciplinary Expert Panel.

Adequate nutrition is an essential factor in healing and immune support in pediatric patients undergoing surgery, but its importance in this setting is not consistently recognized. Standardized institutional nutrition protocols are rarely available, and some clinicians may be unaware of the importance of assessing and optimizing nutritional status. Moreover, some clinicians may be unaware of updated recommendations that call for limited perioperative fasting. Enhanced recovery protocols have been used in adult patients undergoing surgery to ensure consistent attention to nutrition and other support strategies in adult patients before and after surgery, and these are now under evaluation for use in pediatric patients as well. To support better adoption of ideal nutrition delivery, a multidisciplinary panel of experts in the fields of pediatric anesthesiology, surgery, gastroenterology, cardiology, nutrition, and research have gathered and reviewed current evidence and best practices to support nutrition goals in this setting.

Sixth Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: The Society Of Thoracic Surgeons Pedimacs Annual Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2021, there were 1355 devices in 1109 patients (<19 years) from 42 North American Hospitals. RESULTS: Cardiomyopathy was the most common underlying cause (59%), followed by congenital heart disease (25%) and myocarditis (9%). Regarding device type, implantable continuous (IC) VADs were most common at 40%, followed by paracorporeal pulsatile (PP; 28%) and paracorporeal continuous (PC; 26%). Baseline demographics differed, with the PC cohort being younger, smaller, more complex (ie, congenital heart disease), and sicker at implantation (P < .0001). At 6 months after VAD implantation, a favorable outcome (transplantation, recovery, or alive on device) was achieved in 84% of patients, which was greatest among those on IC VADs (92%) and least for PC VADs (69%). Adverse events were not uncommon, with nongastrointestinal bleeding (incidence of 14%) and neurologic dysfunction (11% [stroke, 4%]), within 2 weeks after implantation being the most prevalent. Stroke and bleeding had negative impacts on overall survival (P = .002 and P < .001, respectively). CONCLUSIONS: This Sixth Pedimacs Report demonstrates the continued evolution of the pediatric field. The complexity of cardiac physiologies and anatomic constraint mandates the need for multiple types of devices used (PC, PP, IC). Detailed analyses of each device type in this report provide valuable information to further advance the care of this challenging and vulnerable population.

Hepatorenal dysfunction assessment with the Model for End-Stage Liver Disease Excluding INR score predicts worse survival after heart transplant in pediatric Fontan patients.

BACKGROUND: Fontan physiology results in multiorgan dysfunction, most notably affecting the liver and kidney. We evaluated the utility of Model for End-Stage Liver Disease Excluding INR (MELD-XI) score, a score evaluating the function of both liver and kidney to identify Fontan patients at increased risk for morbidity and mortality post-heart transplant. METHODS: The Pediatric Heart Transplant Society database was queried to identify Fontan patients listed for heart transplant between January 2005 and December 2018. MELD-XI scores were calculated at listing and heart transplant. A multivariable analysis was conducted to identify risk factors for post-heart transplant mortality. Demographic, clinical characteristics, and survival differences were evaluated and compared between the high and low MELD-XI score cohorts. The impact of changing MELD-XI scores during the waitlist period on post-heart transplant outcomes was also evaluated. RESULTS: Of 565 Fontan patients who underwent transplantation, 524 (93%) had calculable MELD-XI scores at the time of heart transplant: 421 calculable at listing and 392 calculable at listing and at heart transplant. On multivariable analysis, only MELD-XI score (squared) (hazard ratio, 1.007), history of protein-losing enteropathy (hazard ratio, 2.1), and ventricular assist device use at transplant (hazard ratio, 3.4) were risk factors for early phase post-heart transplant mortality. Patients with high MELD-XI scores at heart transplant had inferior survival post-heart transplant (P = .02); those in the high MELD-XI score cohort at wait listing and heart transplant tend to have the worst post-heart transplant survival; however, this was not significant (P = .42). CONCLUSIONS: The MELD-XI, an easily calculated score, serves as a valuable aid in identifying pediatric Fontan patients at increased risk for post-heart transplant mortality.

Fifth Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report.

BACKGROUND: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) provides detailed information on pediatric patients supported with ventricular assist devices (VADs). METHODS: From September 19, 2012, to December 31, 2020, 1229 devices in 1011 patients were reported to the registry from 47 North American Hospitals in patients aged younger than 19 years. RESULTS: Cardiomyopathy was the most common underlying etiology (58%), followed by congenital heart disease (CHD; 25%) and myocarditis (10%). The most common devices implanted were implantable continuous (IC; 419 [41%]), followed by paracorporeal pulsatile (PP; 269 [27%]), paracorporeal continuous (PC; 263 [26%]), and percutaneous (53 [5%]). Overall, at 6 months after VAD implantation, 83% had a positive outcome (transplant, explant, or alive on device). The freedom from stroke at 3 months was highest in IC VADs (93%), compared with PP VADs (84%) and with PC VADs (75%). There were differences in survival by device type, with patients on IC VADs having the best overall survival and those on PC having the lowest overall survival, though the patient populations being supported by each VAD type differed significantly from each other. CONCLUSIONS: This Fifth Pedimacs Report demonstrates the continued robust growth of VADs in the pediatric community, now with more than 1000 patients reported to the registry. The multiple available device types (PC, PP, IC) serve different populations with different pre-VAD risk profiles, which may account for differences in survival and adverse events between device types.

Heterogeneous outcomes of liver disease after heart transplantation for a failed Fontan procedure.

BACKGROUND: Fontan-associated liver disease (FALD) uniformly affects patients with long-term Fontan physiology. The effect of isolated heart transplant (HT) on the course of FALD post-HT is not well understood. METHODS: We evaluated serial liver imaging pre- and post-HT to assess liver changes over time in a single-center retrospective analysis of Fontan HT recipients who had pre- and ≥1-year post-HT liver imaging. Available patient demographic and clinical data were reviewed, including available liver biopsy results. RESULTS: Serial liver imaging was available in 19 patients with a median age at HT of 12 years (range 3-23), the median age from Fontan to HT of 5.7 years (range 0.8-16), and the median time from imaging to follow up of 27 months (range 12-136 months). Pre-HT liver imaging was classified as follows: normal (n=1), congested (n=9), fibrotic (n=7), and cirrhotic (n=2). The majority of transplanted patients (15/19) had improvement in their post-HT liver imaging, including 13 patients with initially abnormal imaging pre-HT having normal liver imaging at follow-up. One patient had persistent cirrhosis at 26-month follow-up, one patient had unchanged fibrosis at 18-month follow-up, and one patient progressed from fibrosis pre-HT to cirrhosis post-HT at 136 months. No patients had overt isolated liver failure during pre- or post-HT follow-up. Liver biopsy did not consistently correlate with imaging findings. CONCLUSIONS: Post-HT liver imaging evaluation in Fontan patients reveals heterogeneous liver outcomes. These results not only provide evidence for the improvement of FALD post-HT but also show the need for serial liver imaging follow-up post-HT.

Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplantation.

Data are lacking on RSB intensity and outcomes after pediatric heart transplantation. PHTS centers received a survey on RSB practices from 2005 to present. PHTS data were obtained for 2010-2013 and integrated with center-matched survey responses for analysis. Survey response rate was 82.6% (38/46). Centers were classified as low-, moderate-, and high-intensity programs based on RSB frequency (0-more than 8 RSB/y). RSB intensity decreased with increasing time from HT. Age at HT impacted RSB intensity mostly in year 1, with little to no impact in later years. Most centers have not replaced RSB with non-invasive methods, but many added ECHO and biomarker monitoring. Higher RSB intensity was not associated with decreased 4-year mortality (P=.63) or earlier detection of moderate to severe (ISHLT grade 2R/3R) cellular rejection (RSBMSR) in the first year (P=.87). First-year RSBMSR incidence did not differ with intensity or age at HT. Significant variability exists in RSB intensity, but with no impact on timing and incidence of RSBMSR or 4-year mortality. Reduction in RSB frequency may be safe in certain patients after pediatric HT.

Fontan Patient Survival After Pediatric Heart Transplantation Has Improved in the Current Era.

BACKGROUND: Historically, patients with a prior Fontan procedure for complex congenital heart disease (CHD) have been considered at higher risk for death after heart transplant (HT) compared with other HT transplant candidates. With the overall trend of improved survival of pediatric HT recipients, it is unclear of Fontan patient post-HT survival has also improved in the current era. METHODS: Data from the Pediatric Heart Transplant Study database for Fontan patients who underwent HT was compared between the early era (1993 to 2006, n = 150) and late era (2007 to 2014, n = 252). Post-HT survival and pre-HT characteristics were compared among eras and also with non-Fontan CHD patients. RESULTS: At time of HT, Fontan patients in the late era were more likely to require inotropic support, have protein-losing enteropathy, have failure to thrive, and be further from time of Fontan, although less likely to be on ventilator support. Only ventilator support and earlier year of HT were significant risk factors for death in the multivariate analysis. Post-HT Fontan patient survival significantly improved from the early to late era (p = 0.02), particularly in the early phase, with 1-year survival of 77% in the early era and 89% in the late era. Late era non-Fontan CHD patient 1-year post-HT survival was similar to Fontan patients at 92%. CONCLUSIONS: Survival of Fontan patients after HT has significantly improved in the current era. Currently, expected post-HT survival for Fontan patients is on par with other CHD patients. Fontan patients should not be excluded from consideration for HT solely on a history of Fontan.

Impact of age on incidence and prevalence of moderate-to-severe cellular rejection detected by routine surveillance biopsy in pediatric heart transplantation.

BACKGROUND: The effect of age at transplant on rejection detected by routine surveillance biopsy (RSB) in pediatric heart transplant (HT) recipients is unknown. We hypothesized there would be low diagnostic yield and decreased prevalence of rejection detected on RSB in infants (age <1 year) when compared with children (age 1 to 9 years) and adolescents (age 10 to 18 years). METHODS: We utilized Pediatric Heart Transplant Study (PHTS) data from 2010 to 2013 to analyze moderate-to-severe (ISHLT Grade 2R/3R) cellular rejection (MSR) detected only on RSB (RSBMSR). RESULTS: RSB detected 280 of 343 (81.6%) episodes of MSR. RSBMSR was detected in all age groups even >5 years after HT. Infant RSBMSR had a greater proportion (p = 0.0025) occurring >5 years after HT (39.2 vs 18.4 vs 10.8%) and a lower proportion (p = 0.0009) occurring in the first year after HT (25.5 vs 60.6 vs 51.7%) compared with children and adolescents, respectively. Freedom from RSBMSR was 87 ± 7% in infants, 76 ± 6% in children and 73 ± 7% in adolescents 4 years after HT. In 1-year survivors who had RSBMSR in the first year after HT, the risk of RSBMSR occurring in Years 2 to 4 was significantly (p < 0.0001) greater than patients without RSBMSR in the first year (hazard ratio 21.28, 95% confidence interval 10.87 to 41.66), regardless of recipient age. CONCLUSIONS: RSBMSR exists in all age groups after pediatric HT with long-term follow-up. The prevalence in infant recipients is highest >5 years after HT. Those with RSBMSR in the first year after HT are at a high risk for recurrent rejection regardless of age at HT.

Autoimmunity Against the Heart and Cardiac Myosin in Children With Myocarditis.

BACKGROUND: Host autoimmune activity in myocarditis has been proposed to play a role in development of cardiac disease, but evidence of autoimmunity and relationship to outcomes have not been evaluated in pediatric myocarditis. METHODS: We performed a multi-institutional study of children with clinical myocarditis. Newly diagnosed patients were followed for up to 12 months and previously diagnosed patients at a single follow-up for serum levels of autoantibodies to human cardiac myosin, beta-adrenergic receptors 1 and 2, muscarinic-2 receptors, and antibody-mediated protein kinase A (PKA) activation in heart cells in culture. Results were compared with those of healthy control children. RESULTS: Both previously diagnosed patient at follow-up (P = .0061) and newly diagnosed patients at presentation (P = .0127) had elevated cardiac myosin antibodies compared with control subjects. Antibody levels were not associated with recovery status at follow-up in either group. PKA activation was higher at presentation in the newly diagnosed patients who did not recovery normal function (P = .042). CONCLUSIONS: Children with myocarditis have evidence of autoantibodies against human cardiac myosin at diagnosis and follow-up compared with control subjects. Differences in antibody-mediated cell signaling may contribute to differences in patient outcomes, as suggested by elevated antibody-mediated PKA activation in heart cells by the serum from nonrecovered patients.

High Frequency of Detection by PCR of Viral Nucleic Acid in The Blood of Infants Presenting with Clinical Myocarditis.

Specific viruses are associated with pediatric myocarditis, but the prevalence of viral DNAemia detected by blood polymerase chain reaction (PCR) is unknown. We evaluated the prevalence of known cardiotropic viruses (enterovirus, adenovirus, human herpesvirus 6, and parvovirus B19) in children with clinical myocarditis (n = 21). Results were compared to pediatric controls with similar viral PCR testing. The majority of positive PCR (89 %) was noted in children ≤12 months of age at diagnosis compared to older children. Infant myocarditis patients (8/10) had increased the prevalence of PCR positivity compared to infant pediatric controls (4/114) (p < 0.0001). Other than age, patient characteristics at diagnosis were similar between PCR-positive and PCR-negative patients. Both PCR-negative myocarditis infants had clinical recovery at follow-up. Of the PCR-positive myocarditis infants, 4 had clinical recovery, 2 developed chronic cardiomyopathy, 1 underwent heart transplant, and 1 died. Infants with clinical myocarditis have a high rate of blood viral positivity, which is higher compared to older children with myocarditis and healthy infant controls. Age-related differences in PCR positivity may be due to differences in host and/or virus characteristics. Our findings suggest that viral blood PCR may be a useful diagnostic tool and identify patients who would potentially benefit from virus-specific therapy.

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function.

BACKGROUND: Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. METHODS: We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. RESULTS: CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. CONCLUSIONS: Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population.