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.

Waitlist and post-transplant outcomes for children with myocarditis listed for heart transplantation over 3 decades.

BACKGROUND: There is limited and conflicting information on waitlist and transplant outcomes for children with myocarditis. METHODS: Retrospective review included children with myocarditis and dilated cardiomyopathy (DCM) listed for HT from January 01, 1993 to December 31, 2019 in the Pediatric Heart Transplant Society database. Clinical characteristics, waitlist and post-HT outcomes (graft loss, rejection, cardiac allograft vasculopathy, infection and malignancy) for children listed from early (1993-2008) and current era (2009-2019) with myocarditis were evaluated and compared to those with DCM. RESULTS: Of 9755 children listed, 322 (3.3%) had myocarditis and 3178 (32.6%) DCM. Compared to DCM, children with myocarditis in the early and the current era were significantly more likely to be listed at higher urgency; be in intensive care unit; on mechanical ventilation; extracorporeal membrane oxygenation and ventricular assist device (p < 0.05 for all). While unadjusted analysis revealed lower transplant rates and higher waitlist mortality for children with myocarditis, in multivariable analysis, myocarditis was not a risk factor for waitlist mortality. Myocarditis, however, was a significant risk factor for early phase post-HT graft loss (HR 2.46; p = 0.003). Waitlist and post-HT survival for children with myocarditis were similar for those listed and transplanted in the early era to those listed and transplanted in the current era (p > 0.05 for both). CONCLUSIONS: Children with myocarditis have a higher acuity of illness at listing and at HT and have inferior post-HT survival compared to children with DCM. Outcomes for children with myocarditis have not improved over the 3 decades and efforts are needed to improve outcomes for this cohort.

Systemic ventricular assist device support of the Fontan circulation yields promising outcomes: An analysis of The Society of Thoracic Surgeons Pedimacs and Intermacs Databases.

BACKGROUND: Outcomes of ventricular assist device (VAD) support in patients with Fontan circulatory failure (or failing Fontan physiology) are largely unknown. METHODS: We conducted a retrospective analysis of patients with a Fontan circulation who underwent VAD implant in the Society of Thoracic Surgeons Pedimacs and Intermacs Databases from September 19, 2012, to December 31, 2019. RESULTS: We identified 55 Fontan patients who had undergone VAD implant with a median age at implantation of 10.2 years (interquartile range, 6.4-16.9 years) and weight, 26.8 kg (interquartile range, 17.7-53.8 years). More VADs were implanted in 2018-2019 than in 2012-2017 (28 vs 27; P = .01). The later era had higher pre-VAD glomerular filtration rate (101.1 ± 48.5 vs 71.2 ± 34.9; P = .02); there was no difference in Interagency Registry for Mechanically Assisted Circulatory Support profile (P = .69). Kaplan-Meier survival on device was 76% at 6 months with no difference by era. Competing outcomes demonstrated a positive outcome of 81% (alive on VAD, transplanted, or recovered) at 6 months, with 58% of mortality occurring during month 1. Median length of support was 3.8 months (interquartile range, 0.6-6.9 months). Five patients were supported for >1 year with no added mortality; the longest support time was 4 years, 7 months. Adverse event rates included pump thrombosis incidence of 4% (3.3 out of 100 patient-months), stroke 5.5% (1.4 out of 100 patient-months), gastrointestinal bleeding of 7% (2.6 out of 100 patient-months), and nongastrointestinal bleeding of 9% (2.3 out of 100 patient-months). CONCLUSIONS: This is the largest reported analysis of systemic VAD support of Fontan patients. VAD support of the Fontan circulation is becoming more frequent. This analysis demonstrates that VAD use in this growing population can yield promising outcomes.

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.

Infant Ross-Konno, Endocardial Fibroelastosis Resection and Mitral Valve Repair.

Optimal management of critical aortic stenosis (AS) in infants depends on the left ventricle's (LV's) ability to maintain adequate output. Determining feasibility of biventricular repair may be difficult, particularly in those with mitral disease, endocardial fibroelastosis (EFE), multi-level obstruction, and uncertain physiologic capacity. We report a case of a three-month-old with critical AS, severely reduced LV function, EFE, and moderate mitral regurgitation (MR), who underwent a Ross-Konno procedure with concomitant EFE resection and mitral valve repair. Although the technical sequence is challenging, definitive surgery completely relieved multi-level obstruction and MR with markedly improved LV function.

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.

Waitlist and Post-Heart Transplant Outcomes for Children With Nondilated Cardiomyopathy.

BACKGROUND: Although outcomes for pediatric cardiomyopathy (CMP) patients have improved, an understanding of outcomes by CMP phenotype is essential. This study assessed changes in waitlist and post-transplant survival in nondilated cardiomyopathy (DCM) patients over 2 decades, explored ventricular assist device (VAD) utilization in this cohort, and identified risk factors for waitlist and posttransplant mortality in the current era. METHODS: Pediatric patients with a diagnosis of CMP listed for heart transplantation during three eras: Era 1: March 5, 1999 to December 31, 2004; Era 2: January 1, 2005 to December 15, 2011; and Era 3 (current era): December 16, 2011 to February 28, 2018 were included. Multivariable Cox proportional hazards regression was performed to assess waitlist and posttransplant survival. RESULTS: Compared with patients with DCM, those with hypertrophic and restrictive cardiomyopathy in the current era are less likely to be on VAD (23.4% vs 2.7% vs 4.5%); listed United Network for Organ Sharing Status 1A (75.6% vs 39.8% vs 34.8%), and more likely to have longer waitlist times (P < .01 for all). Only 3.3% hypertrophic and 2.4% restrictive cardiomyopathy patients had VAD implantation, although VAD use did not adversely impact waitlist survival in weighted non-DCM patients. Significant improvements have occurred in waitlist survival of hypertrophic and posttransplant survival of both types of non-DCM patients. CONCLUSIONS: Currently, waitlist and posttransplant survival is similar for all CMP phenotypes. VAD use is low in patients with non-DCM, although this did not increase waitlist mortality in adjusted analysis. Further studies in patients with non-DCM are needed to determine optimal timing and anatomic characteristics most likely to benefit from VAD implantation during the waitlist period.

Strategies to prevent anthracycline-induced cardiotoxicity in cancer survivors.

Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional and newer anti-neoplastic therapies can cause short- and long-term cardiotoxicity. The clinical implications of this cardiotoxicity become more important with the increasing use of cardiotoxic drugs. The implications are especially serious among patients predisposed to adverse cardiac effects, such as youth, the elderly, those with cardiovascular comorbidities, and those receiving additional chemotherapies or thoracic radiation. However, the optimal strategy for preventing and managing chemotherapy-induced cardiotoxicity remains unknown. The routine use of neurohormonal antagonists for cardioprotection is not currently justified, given the marginal benefits and associated adverse events, particularly with long-term use. The only United States Food and Drug Administration and European Medicines Agency approved treatment for preventing anthracycline-related cardiomyopathy is dexrazoxane. We advocate administering dexrazoxane during cancer treatment to limit the cardiotoxic effects of anthracycline chemotherapy.

Reducing radiation exposure by lowering frame rate in children undergoing cardiac catheterization: A quality improvement study.

INTRODUCTION: Reduction of radiation dosage in the pediatric cardiac catheterization laboratory (PCL) is important to reduce the risk of its stochastic effect in children with congenital heart disease. Lowering the frame rate would reduce radiation dosage possibly at the expense of image quality, potentially resulting in higher fluoroscopic time and procedural complication rate. METHODS: The data were retrospectively analyzed in three eras: era 1 (n = 234), cineangiography 30 frames/sec (f/s) and fluoroscopy 15 pulse/sec (p/s); era 2 (n = 381), cineangiography 30 f/s and fluoroscopy 6 p/s; and era 3 (n = 328), cineangiography 15 f/s and fluoroscopy 6 p/s. Also, three operators blinded to the frame rate setting evaluated cineangiography image quality. In this study, the impact of lowering the default frame rates on radiation dosage, fluoroscopic time, contrast volume, diagnostic image quality, and complication rates in the PCL was assessed. RESULTS: Overall radiation dosage progressively declined during these eras (70.0 vs 64.1 vs 36.6 µGym2 /kg, P < .001) without a difference in significant adverse event rates. There was no significant increase in either fluoroscopy time or contrast volume. There was no difference in the diagnostic image quality between cineangiography 30 and 15 f/s. Lowering the default frame/pulse rates of both fluoroscopy and cineangiography significantly decreased the overall radiation dosage in the PCL. Importantly, fluoroscopy time, contrast volume, and complication rates did not increase while maintaining diagnostic image quality. CONCLUSION: This quality improvement project proved successful in lowering radiation dosage without compromising the efficacy and safety of catheterizations.

Cardiovascular disease in survivors of childhood cancer.

PURPOSE OF REVIEW: We review the cardiotoxic chemotherapeutic agents, the clinical and subclinical presentations and progression of their cardiotoxicity, and the management of the subsequent cardiovascular disease in survivors of childhood cancer. We discuss various preventive measures, especially the cardioprotectant, dexrazoxane, whose use with anthracycline chemotherapy, including doxorubicin, is based on strong evidence. Most treatment recommendations for this unique population are based on expert opinion, not on empirical evidence. RECENT FINDINGS: As patients with childhood cancers live longer, morbidity from the cardiac side effects of chemotherapy is increasing. Treatment-related cardiac damage is irreversible and often progressive. It is imperative that such damage be prevented with strategies such as limiting the cumulative anthracycline dose, the use of anthracycline structural analogues and the use of cardioprotective agents. SUMMARY: A deeper understanding of the mechanisms of their cardiotoxicity reveals that there is no 'safe' dose of anthracyclines. However, certain risk factors, such as higher lifetime anthracycline cumulative doses, higher anthracycline dose rates, female sex, longer follow-up, younger age at anthracycline treatment and cardiac irradiation, are associated with more severe cardiotoxicity. We advocate the use of dexrazoxane to limit the cardiotoxic effects of anthracycline chemotherapy.

NT-pro BNP-A marker for worsening respiratory status and mortality in infants and young children with pulmonary hypertension.

AIM: To evaluate predictors of morbidity and mortality in pediatric patients with pulmonary hypertension (PH), laboratory and echocardiographic measures of PH were analyzed. METHODS: A retrospective review of all infants and children < 2 years of age with PH from January 2011 to August 2016 was conducted. Correlations were determined using Spearman's rank correlation coefficients. Differences in characteristics between survivors and nonsurvivors were analyzed and Kaplan-Meier survival curves were generated. RESULTS: Of 56 patients, the majority were extremely premature; of African American ethnicity; and had bronchopulmonary dysplasia. Patients who died were more likely to have underlying congenital heart disease; have a higher increase in the concentration of carbon dioxide in the blood (pCO2 ) with a corresponding greater mean percentage decrease in pH and percentage rise in NT-pro BNP during PH exacerbations; more likely to have been on medications for pulmonary hypertension; and have a higher RVSP/SBP (%) ratio and S/D ratio. There were positive correlations between percentage rise in NT-pro BNP and pCO2 ; NT-pro BNP and RVSP/SBP (%) ratio; and RVSP/SBP (%) ratio and S/D ratio. CONCLUSIONS: Infants and young children with pulmonary hypertension have increased morbidity and mortality. NT-pro BNP is a useful biomarker for both respiratory exacerbations and mortality, and RVSP/SBP (%) ratio and S/D ratio are echocardiographic identifiers for increased mortality.

Chemotherapy-induced cardiotoxicity in children.

INTRODUCTION: With advances in clinical oncology, the burden of morbidity and mortality for cancer survivors due to the cardiac side effects of the chemotherapy is steadily increasing. Treatment-related cardiac damage is progressive and often irreversible. Primary prevention of cardiotoxicity during treatment is possible with strategies like limiting the cumulative anthracycline dose, the use of anthracycline structural analogs, and especially cardioprotective agents. Areas covered: This review covers the various cardiotoxic chemotherapeutic agents, the pathophysiology of cardiotoxicity due to anthracyclines, and the clinical and subclinical presentations and progression of childhood anthracycline cardiotoxicity. We also discuss preventive measures and strategies, especially the cardioprotectant agent dexrazoxane where there is strong evidence-based support for its use with anthracycline chemotherapy. However, there is a paucity of evidence-based recommendations for diagnosing and treating cancer therapy-induced cardiovascular complications. Finally, we discuss the potential of cardio-oncology. Expert opinion: There is no 'safe' anthracycline dose if the goal is normal long-term cardiovascular status but higher lifetime cumulative doses of anthracyclines, higher dose rates, female sex, longer follow-up, younger age at anthracycline treatment, pre-existing cardiovascular disease, and cardiac irradiation are associated with more severe cardiotoxicity. With deeper understanding of the mechanisms of the adverse cardiac effects and identification of driver mutations causing these effects, personalized cancer therapy to limit cardiotoxic effects can be achieved, such as with the cardioprotectant dexrazoxane.