Recommendations for Centers Performing Pediatric Heart Surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Recommendations for centers performing pediatric heart surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Recommendations for Centers Performing Pediatric Heart Surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Development of the Residual Lesion Score for congenital heart surgery: the RAND Delphi methodology.

BACKGROUND AND OBJECTIVE: The Residual Lesion Score is a novel tool for assessing the achievement of surgical objectives in congenital heart surgery based on widely available clinical and echocardiographic characteristics. This article describes the methodology used to develop the Residual Lesion Score from the previously developed Technical Performance Score for five common congenital cardiac procedures using the RAND Delphi methodology. METHODS: A panel of 11 experts from the field of paediatric and congenital cardiology and cardiac surgery, 2 co-chairs, and a consultant were assembled to review and comment on validity and feasibility of measuring the sub-components of intraoperative and discharge Residual Lesion Score for five congenital cardiac procedures. In the first email round, the panel reviewed and commented on the Residual Lesion Score and provided validity and feasibility scores for sub-components of each of the five procedures. In the second in-person round, email comments and scores were reviewed and the Residual Lesion Score revised. The modified Residual Lesion Score was scored independently by each panellist for validity and feasibility and used to develop the "final" Residual Lesion Score. RESULTS: The Residual Lesion Score sub-components with a median validity score of ≥7 and median feasibility score of ≥4 that were scored without disagreement and with low absolute deviation from the median were included in the "final" Residual Lesion Score. CONCLUSION: Using the RAND Delphi methodology, we were able to develop Residual Lesion Score modules for five important congenital cardiac procedures for the Pediatric Heart Network's Residual Lesion Score study.

T Cell Response to Influenza Vaccination Remains Intact in Adults with Congenital Heart Disease Who Underwent Early Thymectomy.

Introduction: T cells developed in the thymus play a key role in vaccine immunity. Thymectomy occurs during infant congenital heart surgery and results in an altered T cell distribution. We investigated if adults with congenital heart disease (ACHD) who underwent early thymectomy have a diminished response to influenza vaccination. Methods: Blood samples from ACHD with early thymectomy ≤ 1 year of age (ACHD-ET; n = 12), no thymectomy (ACHD-NT; n = 8), and healthy controls (HC; n = 14) were collected prior to and 4 weeks after influenza vaccination. Flow cytometric analysis of T cell subsets and vaccine-specific cytokine expressing CD4+ T cells as well as hemagglutination inhibition (HI) assays were completed. Results: The mean age of the cohort was 34 ± 10.6 years and similar in all groups. The mean frequencies of naïve CD4+ and CD8+ T cells were lower in ACHD-ET than in HC (32.7% vs. 46.5%, p = 0.027 and 37.2% vs. 57.4%, p = 0.032, respectively). There was a rise in the frequency of memory CD4+ and CD8+ T cells in the ACHD-ET group. The ACHD-NT had no statistical difference from either group. The frequencies of influenza-specific memory CD4+ T cells expressing IFN-γ and TNF-α were increased after vaccination across all groups (p < 0.05). Conclusions: ACHD-ET have fewer naïve T cells, suggesting immunosenescence. Despite this, they show an adequate T Cell response to vaccination in young adulthood. Our findings support routine vaccination is effective in this population, but research into older ACHD is necessary.

Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease.

Importance: Patients with congenital heart disease (CHD), the most common birth defect, have increased risks for cancer. Identification of the variables that contribute to cancer risk is essential for recognizing patients with CHD who warrant longitudinal surveillance and early interventions. Objective: To compare the frequency of damaging variants in cancer risk genes among patients with CHD and control participants and identify associated clinical variables in patients with CHD who have cancer risk variants. Design, Setting, and Participants: This multicenter case-control study included participants with CHD who had previously been recruited to the Pediatric Cardiac Genomics Consortium based on presence of structural cardiac anomaly without genetic diagnosis at the time of enrollment. Permission to use published sequencing data from unaffected adult participants was obtained from 2 parent studies. Data were collected for this study from December 2010 to April 2019. Exposures: Presence of rare (allele frequency, <1 × 10-5) loss-of-function (LoF) variants in cancer risk genes. Main Outcomes and Measures: Frequency of LoF variants in cancer risk genes (defined in the Catalogue of Somatic Mutations in Cancer-Cancer Gene Consensus database), were statistically assessed by binomial tests in patients with CHD and control participants. Results: A total of 4443 individuals with CHD (mean [range] age, 13.0 [0-84] years; 2225 of 3771 with reported sex [59.0%] male) and 9808 control participants (mean [range] age, 52.1 [1-92] years; 4967 of 9808 [50.6%] male) were included. The frequency of LoF variants in regulatory cancer risk genes was significantly higher in patients with CHD than control participants (143 of 4443 [3.2%] vs 166 of 9808 [1.7%]; odds ratio [OR], 1.93 [95% CI, 1.54-2.42]; P = 1.38 × 10-12), and among CHD genes previously associated with cancer risk (58 of 4443 [1.3%] vs 18 of 9808 [0.18%]; OR, 7.2 [95% CI, 4.2-12.2]; P < 2.2 × 10-16). The LoF variants were also nominally increased in 14 constrained cancer risk genes with high expression in the developing heart. Seven of these genes (ARHGEF12, CTNNB1, LPP, MLLT4, PTEN, TCF12, and TFRC) harbored LoF variants in multiple patients with unexplained CHD. The highest rates for LoF variants in cancer risk genes occurred in patients with CHD and extracardiac anomalies (248 of 1482 individuals [16.7%]; control: 1099 of 9808 individuals [11.2%]; OR, 1.59 [95% CI, 1.37-1.85]; P = 1.3 × 10-10) and/or neurodevelopmental delay (209 of 1393 individuals [15.0%]; control: 1099 of 9808 individuals [11.2%]; OR, 1.40 [95% CI, 1.19-1.64]; P = 9.6 × 10-6). Conclusions and Relevance: Genotypes of CHD may account for increased cancer risks. In this cohort, damaging variants were prominent in the 216 genes that predominantly encode regulatory proteins. Consistent with their fundamental developmental functions, patients with CHD and damaging variants in these genes often had extracardiac manifestations. These data may also implicate cancer risk genes that are repeatedly varied in patients with unexplained CHD as CHD genes.

Adult Congenital Heart Disease-Preparing for the Changing Work Force Demand.

This volume is dedicated to advances in the care of adults with congenital heart disease (CHD). In this chapter the authors review the data cornerstone to the growing workforce needs.This first chapter serves as a backdrop to the second chapter that applies these observations to the planning of health care services delivery in the United States accounting for the definition and organization of multisystem expertise and centers for adults with CHD at a health systems level.

Cancer Risk in Congenital Heart Disease-What Is the Evidence?

As life expectancy in patients with congenital heart disease (CHD) has improved, the risk for developing noncardiac morbidities is increasing in adult patients with CHD (ACHD). Among these noncardiac complications, malignancies significantly contribute to the disease burden of ACHD patients. Epidemiologic studies of cancer risk in CHD patients are challenging because they require large numbers of patients, extended follow-up, detailed and validated clinical data, and appropriate reference populations. However, several observational studies suggest that cancer risks are significantly elevated in patients with CHD compared with the general population. CHD and cancer share genetic and environmental risk factors. An association with exposure to low-dose ionizing radiation secondary to medical therapeutic or diagnostic procedures has been reported. Patients with Down syndrome, as well as, to a lesser extent, deletion of 22q11.2 and renin-angiotensin system pathologies, may manifest both CHD and a predisposition to cancer. Such observations suggest that carcinogenesis and CHD may share a common basis in some cases. Finally, specific conditions, such as Fontan circulation and cyanotic CHD, may lead to multisystem consequences and subsequently to cancer. Nonetheless, there is currently no clear consensus regarding appropriate screening for cancer and surveillance modalities in CHD patients. Physicians caring for patients with CHD should be aware of this potential predisposition and meet screening recommendations for the general population fastidiously. An interdisciplinary and global approach is required to bridge the knowledge gap in this field.

A Pilot Study of Inspiratory Muscle Training to Improve Exercise Capacity in Patients with Fontan Physiology.

While the Fontan procedure has improved life expectancy, patients with single ventricle physiology have impaired exercise capacity due to limited increase in pulmonary blood flow during activity. Enhancing the "thoracic pump" using inspiratory muscle training (IMT) may ameliorate this impairment. Adult nonsmokers with Fontan physiology were recruited through Boston Children's Hospital's outpatient clinic. Participants underwent cardiopulmonary exercise testing and pulmonary function testing, followed by 12 weeks of IMT and then repeat testing. The primary endpoint was change in % predicted peak oxygen consumption (VO2). Secondary endpoints were changes in other exercise metrics. Eleven patients (6 male) were enrolled. Median ages at time of enrollment and Fontan completion were 28.8 years (25.7, 45.5) and 7.8 years (3.9, 16.5), respectively. Average baseline maximal inspiratory pressure (MIP) was normal; only 2 patients had MIP <70% predicted. Peak work rate improved significantly from baseline after 12 weeks of IMT (116.5 ± 45.0 to 126.8 ± 47.0 W, P = 0.019). Peak VO2 tended to improve (baseline 68.1 ± 14.3, change + 5.3 ± 9.6% predicted, P = 0.12), as did VE/VCO2 slope (34.1 ± 6.7 to 31.4 ± 3.6, P = 0.12). There was no change in peak tidal volume or MIP. In a small cohort of Fontan patients with mostly normal MIP, IMT was associated with significant improvement in peak work rate and a trend toward higher peak VO2 and improved ventilatory efficiency. Larger studies are needed to determine if this reflects true lack of effect or whether this pilot study was underpowered for effect size, and whether IMT is more narrowly useful for patients with impaired MIP.

Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures and Malignancy Risk in Adults With Congenital Heart Disease.

BACKGROUND: Adults with congenital heart disease (CHD) are exposed to increasing amounts of low-dose ionizing radiation (LDIR) from cardiac procedures. Cancer prevalence in this population is higher than in the general population. This study estimates the association between LDIR exposure from cardiac procedures and incident cancer in adult patients with CHD. METHODS: The study population derived from the Quebec Congenital Heart Disease Database. We measured cumulative numbers of LDIR-related cardiac procedures for each patient until 1 year before the time of cancer diagnosis or administrative censoring. To assess the association between LDIR exposure and cancer risk, we conducted a nested case-control study and matched cancer cases with controls on sex, CHD severity, birth year, and age. RESULTS: The study included 24 833 adult patients with CHD aged 18 to 64 years from 1995 to 2009. In >250 791 person-years of follow-up, 602 cancer cases were observed (median age, 55.4 years). The cumulative incidence of cancer estimated up to 64 years of age was 15.3% (95% confidence interval [CI], 14.2-16.5). Cases had more LDIR-related cardiac procedures than controls (1410 versus 921 per 1000 adult patients with CHD, P<0.0001). Cumulative LDIR exposure was independently associated with cancer (odds ratio [OR], 1.08 per procedure; 95% CI, 1.04-1.13). Similar results were obtained by using dose estimates for LDIR exposure (OR, 1.10 per 10 mSv; 95% CI, 1.05-1.15) with a possible dose-related response. The effect measure was in the same direction, and the association was persistent for exposure from ≥6 procedures in all sensitivity analyses: after excluding most smoking-related cancer cases (OR, 1.10 per procedure; 95% CI, 1.05-1.16 and OR when exposure from ≥6 procedures, 3.08; 95% CI, 1.77-5.37), and after applying a 3-year lag period (OR, 1.09 per procedure; 95% CI, 1.03-1.14 and OR when exposure from ≥6 procedures: 2.58; 95% CI, 1.43-4.69). CONCLUSIONS: To our knowledge, this is the first large population-based study to analyze and document the association between LDIR-related cardiac procedures and incident cancer in the population of adults with CHD. Confirmations of these findings by prospective studies are needed to reinforce policy recommendations for radiation surveillance in patients with CHD where no regulation currently exists. Physicians ordering and performing cardiac imaging should ensure that exposure is as low as reasonably achievable without sacrificing quality of care.

Fontan-Associated Liver Disease: Proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2015, Washington DC.

Over the past decade, as the majority of patients with single ventricle anatomy who have undergone the Fontan operation reach adulthood, a newly recognized disease process, Fontan-associated liver disease (FALD), has emerged. FALD is an extracardiac complication that may lead to substantial comorbid disease and premature mortality. The risk factors, pathophysiology, longitudinal consequences, and therapeutic options related to FALD remain poorly defined. Although we recognize that Fontan circulatory properties are associated with extracardiac organ dysfunction, numerous gaps in our understanding of the nature of this relationship exist. Such extracardiac manifestations, in addition to other late complications of the circulation, can significantly affect quality of life and healthcare use. Therefore, to initiate a formal evaluation of FALD, the American College of Cardiology (ACC) sponsored a stakeholders meeting on October 1 to 2, 2015, in Washington, DC. The goal of the meeting was to bring together subspecialty experts in the fields of adult and pediatric hepatology, congenital cardiology (adult congenital and pediatric cardiology), heart failure/transplant, epidemiology, and cardiothoracic surgery, as well as patient advocates, patients, parents of children and young adults who have had the Fontan procedure, and research organizations and societies to discuss the current state of FALD. Topics included gaps in knowledge, optimal care, research opportunities and barriers, and sound practices to guide providers, patients, and families. This report summarizes findings from the stakeholders meeting and seeks to establish a platform for understanding and addressing FALD.

Prevalence of Cancer in Adults With Congenital Heart Disease Compared With the General Population.

The prevalence rate of cancer among adult patients with congenital heart disease (CHD) in North America has not been previously described. The Quebec adult CHD database was used to determine the prevalence rate of cancer among adult patients with CHD measured as the number of adults with CHD and cancer alive in 2005 per 1,000 adults with CHD. This prevalence rate was compared with the prevalence rate of cancer in the general population of adults in Canada. Types of cancer among the CHD group were described by gender and age. Adult patients with CHD had a 1.6 to 2 times higher prevalence of cancer at 2, 5, and 10 years for both men and women. Overall, men had a greater prevalence of total cancers in all-time durations than did women. Breast, colon, and prostate cancer were the most common cancers reported in adults with CHD. In conclusion, we observed an increased prevalence of cancer among the adult CHD population of Quebec compared with the general Canadian population.

Exposure to Low-Dose Ionizing Radiation From Cardiac Procedures in Patients With Congenital Heart Disease: 15-Year Data From a Population-Based Longitudinal Cohort.

BACKGROUND: The burden of low-dose ionizing radiation (LDIR) exposure from medical procedures among individuals with congenital heart disease (CHD) is unknown. In this longitudinal population-based study, we sought to determine exposure to LDIR-related cardiac imaging and therapeutic procedures in children and adults with CHD. METHODS AND RESULTS: In an analysis of the Quebec CHD database, exposure to the following LDIR-related cardiac procedures was recorded: catheter-based diagnostic procedures, structural heart interventions, coronary interventions, computed tomography scans of the chest, nuclear procedures, and pacemaker/implantable cardioverter-defibrillator insertion and repair. From 1990 to 2005, there were 16 253 LDIR-exposed patients with CHD with 317 988 patient-years of available follow-up. The total number of LDIR-related procedures increased from 18.5 to 51.9 per 1000 CHD patients per year (P<0.0001). This increase was attributable to increases in rates per 1000 CHD patients in diagnostic cardiac catheterizations (11.7 to 13.7 per 1000), structural heart interventions (1.0 to 5.2 per 1000), coronary interventions (1.0 to 2.4 per 1000), pacemaker/implantable cardioverter-defibrillator insertions (1.6 to 4.4 per 1000), nuclear procedures (4.2 to 13.8 per 1000), and computed tomography scans of the chest (2.5 to 12.3 per 1000). Over time, among children with CHD, the median age at first LDIR procedure decreased from 5.0 years to 9.6 months. Severity of CHD significantly predicted extent of exposure. CONCLUSIONS: From 1990 to 2005, patients with CHD were exposed to increasing numbers of LDIR-emitting cardiac procedures. This exposure occurred at progressively younger ages. These findings provide an important perspective on longitudinal LDIR exposure in this at-risk population.

Hybrid Approach for Off-Pump Pulmonary Valve Replacement in Patients With a Dilated Right Ventricular Outflow Tract.

We describe a hybrid method for minimally invasive pulmonary valve replacement without the use of cardiopulmonary bypass in 3 patients with high surgical risk and dilated right ventricular outflow tracts incompatible with currently available transcatheter devices. This procedure entails surgical creation of a landing zone in the main pulmonary artery through an anterior thoracotomy, followed by transcatheter Melody valve pulmonary valve replacement. Particularly in high-risk patients, this approach may limit morbidity and mortality associated with traditional surgical pulmonary valve replacement.

Hospitalizations and mortality in the United States for adults with Down syndrome and congenital heart disease.

Congenital heart disease (CHD) is common in patients with Down syndrome (DS), and these patients are living longer lives. The aim of this study was to describe the epidemiology of hospitalizations in adults with DS and CHD in the United States. Hospitalizations from 1998 to 2009 for adults aged 18 to 64 years with and without DS with CHD diagnoses associated with DS (atrioventricular canal defect, ventricular septal defect, tetralogy of Fallot, and patent ductus arteriosus) were analyzed using the Nationwide Inpatient Sample. Outcomes of interest were (1) in-hospital mortality, (2) common co-morbidities, (3) cardiac procedures, (4) hospital charges, and (5) length of stay. Multivariate modeling adjusted for age, gender, CHD diagnosis, and co-morbidities. There were 78,793 ± 2,653 CHD admissions, 9,088 ± 351 (11.5%) of which were associated with diagnoses of DS. The proportion of admissions associated with DS (DS/CHD) decreased from 15.2 ± 1.3% to 8.5 ± 0.9%. DS was associated with higher in-hospital mortality (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.4 to 2.4), especially in women (OR 2.4, 95% CI 1.7 to 3.4). DS/CHD admissions were more commonly associated with hypothyroidism (OR 7.7, 95% CI 6.6 to 9.0), dementia (OR 82.0, 95% CI 32 to 213), heart failure (OR 2.2, 95% CI 1.9 to 2.5), pulmonary hypertension (OR 2.5, 95% CI 2.2 to 2.9), and cyanosis or secondary polycythemia (OR 4.6, 95% CI 3.8 to 5.6). Conversely, DS/CHD hospitalizations were less likely to include cardiac procedures or surgery (OR 0.3, 95% CI 0.2 to 0.4) and were associated with lower charges ($23,789 ± $1,177 vs $39,464 ± $1,371, p <0.0001) compared to non-DS/CHD admissions. In conclusion, DS/CHD hospitalizations represent a decreasing proportion of admissions for adults with CHD typical of DS; patients with DS/CHD are more likely to die during hospitalization but less likely to undergo a cardiac procedure.