Heart Transplantation for Pediatric and Congenital Cardiac Disease: A Comparison of Two Eras over 23 Years and 188 Transplants at a Single Institution.

BACKGROUND: To assess changes in patterns of practice and outcomes over time, we reviewed all patients who underwent heart transplantation (HTx) at our institution and compared two consecutive eras with significantly different immunosuppressive protocols (cohort 1 [80 HTx, June 1995-June 2006]; cohort 2 [108 HTx, July 2006-September 2018]). METHODS: Retrospective study of 180 patients undergoing 188 HTx (June 1995-September 2018; 176 first time HTx, 10 second HTx, and 2 third HTx). In 2006, we commenced pre-HTx desensitization for highly sensitized patients and started using tacrolimus as our primary postoperative immunosuppressive agent. The primary outcome was mortality. Survival was modeled by the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard models were created to identify prognostic factors for survival. RESULTS: Our 188 HTx included 18 neonates, 85 infants, 83 children, and 2 adults (>18 years). Median age was 260.0 days (range: 5 days-23.8 years). Median weight was 7.5 kg (range: 2.2-113 kg). Patients in cohort 1 were less likely to have been immunosensitized preoperatively (12.5% vs 28.7%, P = .017). Nevertheless, Kaplan-Meier analysis suggested superior survival in cohort 2 (P = .0045). Patients in cohort 2 were more likely to be alive one year, five years, and ten years after HTx. Multivariable analysis identified the earlier era (hazard ratio [HR] [95% confidence interval] for recent era = 0.32 [0.14-0.73]), transplantation after prior Norwood operation (HR = 4.44 [1.46-13.46]), and number of prior cardiac operations (HR = 1.33 [1.03-1.71]) as risk factors for mortality. CONCLUSIONS: Our analysis of 23 years of pediatric and congenital HTx reveals superior survival in the most recent 12-year era, despite the higher proportion of patients with elevated panel reactive antibody in the most recent era. This improvement was temporally associated with changes in our immunosuppressive strategy.

Development and impact of arrhythmias after the Norwood procedure: A report from the Pediatric Heart Network.

OBJECTIVES: The study objective was to determine the predictors of new-onset arrhythmia among infants with single-ventricle anomalies during the post-Norwood hospitalization and the association of those arrhythmias with postoperative outcomes (ventilator time and length of stay) and interstage mortality. METHODS: After excluding patients with preoperative arrhythmias, we used data from the Pediatric Heart Network Single Ventricle Reconstruction Trial to identify risk factors for tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia, junctional ectopic tachycardia, and ventricular tachycardia) and atrioventricular block (second or third degree) among 544 eligible patients. We then determined the association of arrhythmia with outcomes during the post-Norwood hospitalization and interstage period, adjusting for identified risk factors and previously published factors. RESULTS: Tachyarrhythmias were noted in 20% of subjects, and atrioventricular block was noted in 4% of subjects. Potentially significant risk factors for tachyarrhythmia included the presence of modified Blalock-Taussig shunt (P = .08) and age at Norwood (P = .07, with risk decreasing each day at age 8-20 days); the only significant risk factor for atrioventricular block was undergoing a concomitant procedure at the time of the Norwood (P = .001), with the greatest risk being in those undergoing a tricuspid valve procedure. Both tachyarrhythmias and atrioventricular block were associated with longer ventilation time and length of stay (P < .001 for all analyses). Tachyarrhythmias were not associated with interstage mortality; atrioventricular block was associated with mortality among those without a pacemaker in the unadjusted analysis (hazard ratio, 2.3; P = .02), but not after adding covariates. CONCLUSIONS: Tachyarrhythmias are common after the Norwood procedure, but atrioventricular block may portend a greater risk for interstage mortality.

Hospital Charges for Pediatric Heart Failure-Related Hospitalizations from 2000 to 2009.

Scarce data exist regarding costs of pediatric heart failure-related hospitalizations (HFRH) or how costs have changed over time. Pediatric HFRH costs, due to advances in management, will have increased significantly over time. A retrospective analysis of Healthcare Cost and Utilization Project Kids' Inpatient Database was performed on all pediatric HFRH. Inflation-adjusted charges are used as a proxy for cost. There were a total of 33,189 HFRH captured from 2000 to 2009. Median charges per HFRH rose from $35,079 in 2000 to $72,087 in 2009 (p < 0.0001). The greatest median charges were incurred in patients on extracorporeal membrane oxygenation ($442,134 vs $53,998) or ventricular assist devices ($462,647 vs $55,151). Comorbidities, including sepsis ($207,511 vs $48,995), renal failure ($180,624 vs $52,812), stroke ($198,260 vs $54,974) and respiratory failure ($146,200 vs $48,797), were associated with greater charges (p < 0.0001). Comorbidities and use of mechanical support increased over time. After adjusting for these factors, later year remained associated with greater median charges per HFRH (p < 0.0001). From 2000 to 2009, there has been an almost twofold increase in pediatric HFRH charges, after adjustment for inflation. Although comorbidities and use of mechanical support account for some of this increase, later year remained independently associated with greater charges. Further study is needed to understand potential factors driving these higher costs over time and to identify more cost-effective therapies in this population.

Efficacy of digoxin in comparison with propranolol for treatment of infant supraventricular tachycardia: analysis of a large, national database.

INTRODUCTION: Digoxin or propranolol are used as first-line enteral agents for treatment of infant supraventricular tachycardia. We used a large national database to determine whether enteral digoxin or propranolol was more efficacious as first-line infant supraventricular tachycardia therapy. MATERIALS AND METHODS: The Pediatric Health Information System database was queried over 10 years for infants with supraventricular tachycardia initiated on enteral digoxin or propranolol monotherapy. Patients were excluded for Wolff-Parkinson-White, intravenous antiarrhythmics (other than adenosine), or death. Success was considered as discharge on the initiated monotherapy. Risk factors for successful monotherapy and risk factors for readmission for supraventricular tachycardia for patients discharged on monotherapy were determined. RESULTS: A total of 374 patients (59.6% male) met the study criteria. Median length of stay was 7 days (interquartile range of 3-16 days). Patients had CHD (n=199, 53.2%) and underwent cardiac surgery (n=123, 32.9%), ICU admission (n=238, 63.6%), mechanical ventilation (n=146, 39.0%), and extracorporeal membrane oxygenation (n=3, 0.8%). Pharmacotherapy initiation was at median 37 days of life (interquartile range of 12-127 days) and 47.3% were initiated on digoxin. Success was similar between digoxin (73.1%) and propranolol (73.5%). Initial therapy with digoxin was not associated with success (odds ratio 1.01, 95% CI 0.64-1.61, p=0.93). Multivariable analysis demonstrated hospital length of stay (odds ratio 0.98, 95% CI 0.98-1.00) and involvement of a paediatric cardiologist (odds ratio 0.46, 95% CI 0.29-0.75) associated with monotherapy failure, and male gender (odds ratio 1.66, 95% CI 1.03-2.67) associated with monotherapy success. No variables were significant for readmission on multivariable analysis. DISCUSSION: Digoxin or propranolol may be equally efficacious for inpatient treatment of infant supraventricular tachycardia.

Arrhythmias in paediatric valvar disease.

Valvar heart disease can be complicated by hemodynamic derangements, depending on the degree of the abnormality. Stenosis causes pressure overload of the chamber draining through the valve and regurgitation results in volume overload. Many lesions have a component of both, resulting in both pressure and volume overload. Increased wall stress causes myocardial stretching and fibrosis, resulting in scarring; a nidus for arrhythmia development. Arrhythmias can complicate the clinical picture and increase the morbidity and mortality in patients with both congenital and acquired valvar disease. In adults with congenital heart disease, arrhythmias are the most common cause of sudden death, followed by heart failure. Valvar stenosis and insufficiency certainly contribute to this. This article highlights the need for arrhythmia surveillance for high-risk valvar lesions.

Development of paediatric electrophysiology standards for Florida Children's Medical Services.

The Florida Children's Medical Services (CMS) has a long-standing history of ensuring that providers of multiple paediatric subspecialties abide by the highest standards. The cardiac sub-committee has written quality standard documents that participating programmes must meet or exceed. These standards oversee paediatric cardiology services including surgery, catheterisations, and outpatient services. On April, 2012, the cardiac sub-committee decided to develop similar standards in paediatric electrophysiology. A task force was created and began this process. These standards include a catalogue of required and optional equipment, as well as staff and physician credentials. We sought to establish expectations of procedural numbers by practitioner and facility. The task force surveyed the members of the Pediatric and Congenital Electrophysiology Society. Finding no consensus, the task force is committed to generate the data by requiring that the CMS participating programmes enrol and submit data to the Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT™) Initiative. This manuscript details the work of the Florida CMS Paediatric Electrophysiology Task Force.

Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center.

BACKGROUND: Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death. METHODS AND RESULTS: We retrospectively reviewed all children diagnosed with left ventricular noncompaction at Texas Children's Hospital from January 1990 to January 2009. Patients with congenital cardiac lesions were excluded. Two hundred forty-two children were diagnosed with isolated left ventricular noncompaction over the study period. Thirty-one (12.8%) died, and 13 (5.4%) were received a transplant. One hundred fifty (62%) presented with or developed cardiac dysfunction. The presence of cardiac dysfunction was strongly associated with mortality (hazard ratio, 11; P<0.001). ECG abnormalities were present in 87%, with ventricular hypertrophy and repolarization abnormalities occurring most commonly. Repolarization abnormalities were associated with increased mortality (hazard ratio, 2.1; P=0.02). Eighty children (33.1%) had an arrhythmia, and those with arrhythmias had increased mortality (hazard ratio, 2.8; P=0.002). Forty-two (17.4%) had ventricular tachycardia, with 5 presenting with resuscitated sudden cardiac death. In total, there were 15 cases of sudden cardiac death in the cohort (6.2%). Nearly all patients with sudden death (14 of 15) had abnormal cardiac dimensions or cardiac dysfunction. No patient with normal cardiac dimensions and function without preceding arrhythmias died. CONCLUSIONS: Left ventricular noncompaction has a high mortality rate and is strongly associated with arrhythmias in children. Preceding cardiac dysfunction or ventricular arrhythmias are associated with increased mortality. Children with normal cardiac dimensions and normal function are at low risk for sudden death.

Management of arrhythmias in patients with a tetralogy of Fallot.

Although arrhythmias are commonly found in patients with all different types of congenital heart disease, perhaps no patient is at higher risk of late development of arrhythmias that may result in sudden death than in the patient following tetralogy of Fallot repair. Despite major improvement in the surgical repair of this disease, a significant percentage of these patients continue to remain at risk for the late development of arrhythmias, and a small percentage will develop life-threatening arrhythmias and sudden death. Which patients remain at highest risk is still not clearly delineated. Diligent arrhythmia surveillance and aggressive treatment strategies are necessary to minimise this risk. This article highlights important strategies to manage arrhythmia development and prevention in this patient population.

Prevalence, morbidity, and mortality of heart failure-related hospitalizations in children in the United States: a population-based study.

BACKGROUND: Few data exist on prevalence, morbidity, and mortality of pediatric heart failure hospitalizations. We tested the hypotheses that pediatric heart failure-related hospitalizations increased over time but that mortality decreased. Factors associated with mortality and length of stay were also assessed. METHODS AND RESULTS: A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed for pediatric (age ≤18 years) heart failure-related hospitalizations for the years 1997, 2000, 2003, and 2006. Hospitalizations did not significantly increase over time, ranging from 11,153 (95% confidence interval [CI] 8,898-13,409) in 2003 to 13,892 (95% CI 11,528-16,256) in 2006. Hospital length of stay increased from 1997 (mean 13.8 days, 95% CI 12.5-15.2) to 2006 (mean 19.4 days, 95% CI 18.2 to 20.6). Hospital mortality was 7.3% (95% CI 6.9-8.0) and did not vary significantly between years; however, risk-adjusted mortality was less in 2006 (odds ratio 0.70, 95% CI 0.61 to 0.80). The greatest risk of mortality occurred with extracorporeal membrane oxygenation, acute renal failure, and sepsis. CONCLUSIONS: Heart failure-related hospitalizations occur in 11,000-14,000 children annually in the United States, with an overall mortality of 7%. Many comorbid conditions influenced hospital mortality.

Magnetic versus manual catheter navigation for ablation of free wall accessory pathways in children.

BACKGROUND: Transcatheter ablation of accessory pathway (AP)-mediated tachycardia is routinely performed in children. Little data exist regarding the use of magnetic navigation (MN) and its potential benefits for ablation of AP-mediated tachycardia in this population. METHODS AND RESULTS: We performed a retrospective review of prospectively gathered data in children undergoing radiofrequency ablation at our institution since the installation of MN (Stereotaxis Inc, St. Louis, MO) in March 2009. The efficacy and safety between an MN-guided approach and standard manual techniques for mapping and ablation of AP-mediated tachycardia were compared. During the 26-month study period, 145 patients underwent radiofrequency ablation for AP-mediated tachycardia. Seventy-three patients were ablated with MN and 72 with a standard manual approach. There were no significant differences in demographic factors between the 2 groups with a mean cohort age of 13.1±4.0 years. Acute success rates were equivalent with 68 of 73 (93.2%) patients in the MN group being successfully ablated versus 68 of 72 (94.4%) patients in the manual group (P=0.889). During a median follow-up of 21.4 months, there were no recurrences in the MN group and 2 recurrences in the manual group (P=0.388). There were no differences in time to effect, number of lesions delivered, or average ablation power. There was also no difference in total procedure time, but fluoroscopy time was significantly reduced in the MN group at 14.0 (interquartile range, 3.8-23.9) minutes compared with the manual group at 28.1 (interquartile range, 15.3-47.3) minutes (P<0.001). There were no complications in either group. CONCLUSIONS: MN is a safe and effective approach to ablate AP-mediated tachycardia in children.

Hospital charges for pediatric heart transplant hospitalizations in the United States from 1997 to 2006.

BACKGROUND: Heart transplantation remains a resource-intensive therapy for children. However, data regarding change in costs over time are scarce. We tested the hypothesis that hospital charges for pediatric heart transplant hospitalizations would increase from 1997 to 2006 and assessed factors associated with hospital charges. METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Database was performed on admissions surrounding heart transplantation for the years 1997, 2000, 2003, and 2006. The database is a nationwide sampling of pediatric hospital discharges and is weighted to provide national estimates. RESULTS: There were 353 (95% confidence interval, 201-505) pediatric heart transplants in 1997 and 355 (95% confidence interval, 226-485) in 2006. Mean hospital charges increased from $279,399 in 1997 to $451,738 in 2006 (p < 0.001). This increase was similar to that observed for other pediatric surgical diseases. Increases also occurred in morbidities, including pulmonary hypertension (p = 0.04) and sepsis (p = 0.04), and in the use of extracorporeal membrane oxygenation (p = 0.03). On multivariable analysis, greater hospital charges were associated with later calendar year (p = 0.001), stroke (p = 0.03), sepsis (p = 0.001), renal failure (p = 0.008), arrhythmia (p = 0.03), and use of extracorporeal membrane oxygenation (p < 0.001) and ventricular assist device (p < 0.001). CONCLUSIONS: From 1997 to 2006, mean charges for pediatric heart transplant hospitalizations increased by > $170,000 (160%). Although greater morbidities in the later years of the study potentially contributed to increased charges, later calendar year was independently associated with increased charges. The changes in charges for heart transplant are similar to the increases seen in other surgical procedures. Ongoing study of management strategies is needed to determine cost-effective therapies for this complex group of patients.

Arrhythmia management in patients with a common arterial trunk and d-transposition of the great arteries.

Arrhythmias in patients with congenital heart disease present a challenge to the care of these patients and can result in significant morbidity and mortality. Transposition of the great arteries and common arterial trunk are no exceptions. It is important to identify risk factors for arrhythmia development in the peri-operative period. The peri-operative arrhythmia burden may relate to the underlying congenital heart disease, haemodynamic perturbations, operative events, and potential residual lesions. In addition, these patients are at risk for developing arrhythmias later in life, and non-invasive and potentially invasive arrhythmia surveillance should be a routine part of the care of these patients. This article highlights important strategies to manage arrhythmia development and prevention in this patient population.

Ultrasound dilution: an accurate means of determining cardiac output in children.

BACKGROUND: Cardiac output is a useful measure of myocardial performance. Cardiac output monitoring is frequently performed in critically ill adults to guide physicians' treatment strategies. However, standard methods of determining cardiac output in children are not without risk and can be problematic secondary to their invasive nature and other technical problems. The COstatus system (Transonic Systems, NY), which is based on ultrasound dilution technology, works off in situ catheters and uses an innocuous indicator to allow for routine measurements of cardiac output and blood volumes in pediatric patients. The purpose of this study was to validate cardiac output measured by the COstatus system with those obtained by the clinical standard technique of pulmonary artery thermodilution. METHODS: This was a prospective evaluation performed at a single institution. Any child with a structurally normal heart undergoing hemodynamic evaluation in the cardiac catheterization laboratory was included. A prograde right heart catheterization was performed, and cardiac output was first determined by using the pulmonary artery thermodilution technique. Thermodilution results were then compared with cardiac output measurements obtained using the COstatus system. The results were analyzed by standard correlation, Bland-Altman, and Critchley and Critchley analyses. RESULTS: Twenty-eight patients were evaluated with a median age of 8 yrs and a median weight of 31 kg. The mean thermodilution cardiac index = 3.18 L/min (± 1.35 L/min), and the mean COstatus system cardiac index = 3.17 L/min (± 1.31 L/min). Standard Pearson correlation tests revealed an excellent correlation coefficient of 0.95 (p < .0001). Bland-Altman analysis revealed good clinical agreement with a mean difference of -0.004 L/min with a precision of 0.8 L/min at 2 SD. A percentage error of 25.4% was noticed in this study, which is less than the clinically acceptable limit. CONCLUSION: The ultrasound dilution technique of determining cardiac output using the COstatus system provides a less invasive method than the traditional pulmonary artery thermodilution for accurately determining cardiac output in children. This is the first validation of the COstatus system in pediatric patients. Further studies are required to establish its accuracy in pediatric patients with cardiac shunts and other hemodynamically unstable conditions.

Restrictive physiology is associated with poor outcomes in children with hypertrophic cardiomyopathy.

Pediatric patients with hypertrophic cardiomyopathy (HCM) and restrictive physiology (RP) with poor outcomes have been identified, but data on their course are limited. Our goal was to delineate the clinical features and course of children with HCM and RP. An institutional review of 119 patients identified between 1985 and 2010 with the diagnosis of HCM was performed. The diagnosis of RP was based on >1 echocardiogram along with at least one of the following: left atrial enlargement without evidence of left ventricle dilation, E/E' ratio ≥ 10, and E/A ratio ≥ 3. Outcomes analysis was performed using Cox or Poisson regression when appropriate. RP was present in 50 (42%) patients. In patients without RP, 10-year freedom-from-death or aborted sudden cardiac death (aSCD), and death or heart transplant (HT), were 93.6 and 98.5%, respectively. In patients with RP, 10-year freedom-from-death or aSCD, and death or HT, were 59.0 and 71.2%, respectively. RP conferred a 3.5-fold increase in incidence rate of hospitalization (P = 0.01), a 3.8-fold increase in hazard of death or aSCD (P = 0.02), and a 5.7-fold increase in hazard of death or HT (P = 0.04). Assessment for RP is of paramount importance in children with HCM because those without RP have a good prognosis, and those with RP account for the majority of poor outcomes.

Effectiveness of mechanical circulatory support in children with acute fulminant and persistent myocarditis.

BACKGROUND: Acute fulminant myocarditis is a life-threatening disease in children. A limited number of reports suggest that mechanical circulatory support (MCS) may be used to successfully bridge children with acute fulminant myocarditis to recovery or transplantation. We evaluated the effectiveness of MCS in children with myocarditis and identified risk factors associated with adverse outcomes. METHODS AND RESULTS: Between 2001 and 2009, 16 children were treated for myocarditis at our institution; each child received MCS provided by extracorporeal membrane oxygenation, ventricular assist device(s), or both. Of these patients, 75% (12/16) survived: 7 recovered ventricular function, and 5 underwent successful orthotopic heart transplantation. In patients who were bridged to recovery, mean left ventricular ejection fraction significantly improved from initiation to termination of MCS (20 ± 9.3% to 62 ± 5%; P = .0004). Viral pathogens were detected in 11 patients by polymerase chain reaction, and viral presence was associated with death or need for transplantation (P = .011). Upon histologic analysis, absence of viral infection and lack of myocardial inflammation were associated with recovery (P values .011 and .044, respectively). CONCLUSIONS: In children with acute fulminant and persistent myocarditis, MCS is a life-saving treatment strategy, particularly in the absence of viral infection.

Impact of the American Heart Association scientific statement on screening electrocardiograms and stimulant medications.

OBJECTIVE: To evaluate the impact of the American Heart Association (AHA) scientific statement regarding electrocardiograms (ECGs) and stimulant medications on the practice of community pediatricians. DESIGN: Retrospective evaluation and survey analysis. SETTING: Academic tertiary care center. PARTICIPANTS: Patients with ECGs referred to our institution by pediatricians with an indication of stimulant medication screening in the year after the AHA statement. INTERVENTION: We compared the ECG ordering practices of community pediatricians and the outcomes of further evaluation and estimated the associated cost before and after the AHA scientific statement. MAIN OUTCOME MEASURES: Abnormal ECG findings, further workup, and change in clinical practice. RESULTS: In the year after publication of the 2008 AHA scientific statement, 372 ECGs were ordered with an indication of stimulant medication screening. Before publication of this statement, a mean (SD) of 6.9 (3.2) ECGs per month were referred for this indication. Despite continuing controversy, this number increased 4-fold to 31.2 (9.5) ECGs per month in the subsequent year. Twenty-four ECGs (6.4%) had abnormal findings. Eighteen patients were referred for further evaluation, and, at last follow-up, none had been found to have definitive disease. Six of 24 patients with abnormal ECG findings (25.0%) had a perceived significant delay in therapy because of the process. In responding pediatricians, 34.6% reported that the scientific statement had clearly affected their practice. CONCLUSIONS: The clinical practice of community pediatricians in regard to screening ECGs and stimulant medications has been affected by the recent AHA scientific statement. The yield of performing ECGs with an indication of stimulant medication screening is very low.

Electrocardiographic abnormalities and arrhythmias are strongly associated with the development of cardiomyopathy in muscular dystrophy.

BACKGROUND: Dilated cardiomyopathy (DCM) is a well-recognized sequela of muscular dystrophy (MD). Early identification of cardiac involvement with timely therapy can favorably impact outcome. We hypothesize that electrocardiography (ECG) can be a useful adjunct in the identification of DCM in MD. OBJECTIVE: This study sought to assess the utility of electrocardiography in patients with MD. METHODS: A retrospective review of patients with MD was performed. ECGs and Holter monitor results were analyzed to assess for association between abnormalities and the development of DCM. RESULTS: This study identified 150 patients. In 43% of patients (64 of 150) DCM developed. ECG abnormalities were found in 65% of patients and correlated well with the presence of DCM, with 60 of 64 (94%) with DCM having an abnormal ECG vs. 38 of 86 (44%) without DCM (P < .001). Only 4 of 52 (8%) of patients with normal ECGs had DCM. The presence of ECG abnormalities was highly sensitive (95.8%) but not specific (40.1%) to the presence of DCM. ECG abnormalities often preceded the development of DCM by a significant period of time (3.7 ± 2.6 years). Arrhythmias were common, with 17 of 150 (11%) of the cohort being affected. Those with DCM were significantly more likely to have an arrhythmia, with 16 of 64 (25%) of that group being affected (P < .01). The presence of VT was a poor prognostic indicator, with 6 of 11 patients dying within 0.68 ± 0.41 years. CONCLUSION: ECG abnormalities are strongly associated with DCM in patients with MD and frequently precede cardiac dysfunction by several years. Arrhythmias are common, and periodic ECG and Holter evaluations are warranted as they may predict early cardiac involvement.