Cumulative Radiation Exposure and Lifetime Cancer Risk in Patients With Tetralogy of Fallot Requiring Early Intervention.

Background: Neonates with tetralogy of Fallot and symptomatic cyanosis (sTOF) require early intervention, utilizing either a staged repair (SR) or primary repair (PR) approach. They are exposed to several sources of low-dose ionizing radiation, which may contribute to increased cancer risk. Objectives: The purpose of this study was to compare cumulative radiation exposure and associated lifetime attributable risk (LAR) of cancer between treatment strategies in sTOF. Methods: Neonates with sTOF who underwent SR or PR from 2012 to 2017 were retrospectively reviewed from the Congenital Cardiac Research Collaborative. Radiation exposure from all radiologic studies prior to 18 months of age was converted to organ-equivalent doses and projected LAR of cancer incidence using the National Cancer Institute dosimetry tools. Results: There were 242 neonates from 8 centers, including patients with 146 SR and 96 PR. Cumulative total effective dose was significantly higher for SR (median 8.3 mSv, IQR: 3.0-17.4 mSv) than PR (2.1 mSv, IQR: 0.8-8.5 mSv; P < 0.001). Cumulative organ-level doses were significantly higher in SR compared to PR. Regardless of treatment strategy, LARs were higher in females compared to males. Among organs with median exposure >1 mGy in females, the LAR was highest for breast in SR (mean 1.9/1,000 patients). The highest proportion of cancers attributable to radiation exposure was projected for thyroid cancer in females undergoing SR (7.3%). Conclusions: Cumulative radiation exposure and LARs were higher among those undergoing SR compared to PR. This will be an important factor to consider in determining the preferred neonatal treatment strategy and should substantiate efforts to reduce radiation exposure in this vulnerable population.

Meta-analysis: Incidence of cirrhosis and hepatocellular carcinoma in patients with Fontan palliation.

BACKGROUND AND AIMS: The Fontan palliation is the final stage of surgery for many children born with univentricular physiology. Almost all Fontan patients develop liver fibrosis which may eventually lead to cirrhosis and hepatocellular carcinoma (HCC). These are important causes of morbidity and mortality in these patients. We performed a systematic review and meta-analysis to assess the incidence of cirrhosis and HCC in Fontan patients and stratify it based on time since surgery. METHODS: A literature search of seven databases identified 1158 records. Studies reporting the number of cirrhosis and HCC cases in Fontan patients and time since Fontan surgery were included. In the cirrhosis cohort, we included only those studies where all patients underwent liver biopsy. RESULTS: A total of 23 studies were included: 12 and 13 studies in the cirrhosis and HCC cohorts, respectively, with two studies included in both cohorts. The incidence of cirrhosis was 0.97 per 100 patient-years (95% CI 0.57-1.63), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 1.61 per 100 patient-years (95% CI 1.24-2.08) and 32.2% (95% CI 25.8%-39.4%), respectively. The incidence of HCC was 0.12 per 100 patient-years (95% CI 0.07-0.21), with the incidence and cumulative incidence ≥20 years post Fontan surgery being 0.20 per 100 patient-years (95% CI 0.12-0.35) and 3.9% (95% CI 2.2%-6.8%), respectively. Only about 70% of patients with HCC (20/28) had underlying cirrhosis. CONCLUSION: The incidence of cirrhosis and HCC increases over time, especially at ≥20 years post Fontan surgery. Studies are needed to further identify at-risk patients in order to streamline surveillance for these highly morbid conditions.

Cardiac magnetic resonance haemodynamics in paediatric heart transplant patients: fick oximetry versus cardiac magnetic resonance phase contrast.

BACKGROUND: Lifetime radiation exposure for paediatric orthotopic heart transplant (OHT) patients is significant with cardiac catheterisation as the dominant source. Interventional cardiac magnetic resonance is utilised to obtain simultaneous, radiation-free haemodynamics and flow/function measurements. We sought to compare invasive haemodynamic measurements and radiation exposure in traditional cardiac catheterisation, to comprehensive interventional cardiac magnetic resonance. METHODS: Twenty-eight OHT patients who underwent 67 interventional cardiac magnetic resonance procedures at Children's National Hospital were identified. Both invasive oximetry with peripheral oxygen saturation (Fick) and cardiac magnetic resonance phase contrast measurements of pulmonary and systemic blood flow were performed. Systemic and pulmonary blood flow from the two modalities was compared using Bland-Altman, concordance analysis, and inter-reader correlation. A mixed model was implemented to account for confounding variables and repeat encounters. Radiation dosage data were collected for a contemporaneous cohort of orthotopic heart transplant patients undergoing standard, X-ray-guided catheterisation. RESULTS: Simultaneous cardiac magnetic resonance and Fick have poor agreement in our study based on Lin's correlation coefficient of 0.68 and 0.73 for pulmonary and systemic blood flow, respectively. Bland-Altman analysis demonstrated a consistent over estimation of cardiac magnetic resonance cardiac output by Fick. The average indexed dose area product for patients undergoing haemodynamics with endomyocardial biopsy was 0.73 (SD ±0.6) Gy*m2/kg. With coronary angiography added, the indexed dose area product was 14.6 (SD ± 7.8) Gy*m2/kg. CONCLUSIONS: Cardiac magnetic resonancemeasurements of cardiac output/index in paediatric orthotopic heart transplant patients have poor concordance with Fick estimates; however, cardiac magnetic resonance has good internal validity and inter-reader reliability. Radiation doses are small for haemodynamics with biopsy and increase exponentially with angiography, identifying a new target for cardiac magnetic resonance imaging.

Hybrid strategy in neonates with ductal-dependent systemic circulation and multiple risk factors.

OBJECTIVE: The study objective was to analyze outcomes of the hybrid strategy for ductal-dependent systemic circulation consisting of bilateral pulmonary artery banding with or without ductal stenting followed by delayed Norwood-type palliation or comprehensive stage II operation in high-risk neonates. METHODS: A retrospective analysis was performed between December 2017 and March 2021. Thirty high-risk neonates underwent palliation with bilateral pulmonary artery banding: 11 with prostaglandin therapy and 19 with ductal stenting. Median (range) age and body weight of patients at hybrid stage I were 3 days (0-43) and 2.9 kg (1.1-4.2), respectively. Operative and interstage mortality, morbidity, and reintervention rates were assessed. RESULTS: Overall survival was 70% (21/30) at a median follow-up time of 9 months (range, 0-37) from hybrid stage I. Operative survival for hybrid stage I was 90% (27/30), of which 2 patients received palliative care, and there was 1 interstage death (4%, 1/27). After hybrid stage I, 37% of patients had a reintervention, and 3% (n = 1) used extracorporeal membrane oxygenation before the next stage of repair. Five patients are awaiting second-stage operation, and 9 patients are awaiting Fontan completion. CONCLUSIONS: High-risk neonates with hypoplastic left heart syndrome or its variants can be successfully palliated using the hybrid strategy and bridged to a delayed Norwood or comprehensive stage II operation with satisfactory survival. This operative approach is a promising alternative pathway for neonates deemed to be high risk due to multiple preoperative risk factors.

Spontaneous rupture of a coronary artery fistula presenting with post-exertional syncope and haemopericardium.

An 8-year-old with a known diagnosis of an asymptomatic coronary artery fistula (CAF) presented with exertional syncope and haemopericardium due to contained rupture of CAF. A transcatheter closure was attempted, but the fistula ruptured again prompting emergency surgical repair. Spontaneous rupture is a catastrophic complication of CAF and warrants a high index of suspicion, timely diagnosis and team management.

Diagnosis and management of the adult patient with a failing Fontan circulation.

Since the original description, the Fontan operation has been widely used for the palliation of children with single ventricle physiology. Although the Fontan operation revolutionized the survival rates of patients with single ventricle physiology, it carries an inevitable risk for long-term morbidity and mortality that impacts clinical outcomes and quality of life. This review will focus on the evaluation and treatment of the patient with the failing Fontan phenotype, with an emphasis on creating an individualized treatment plan.

Reintervention Burden and Vessel Growth After Surgical Reimplantation of a Pulmonary Artery During Childhood.

Children requiring reimplantation of a branch pulmonary artery (PA) are at risk for postoperative stenosis and impaired growth of the reimplanted PA. Outcomes and risk factors for reintervention and impaired growth are incompletely described. We reviewed data on patients who underwent reimplantation of a branch PA between 1/1/99 and 5/1/15 at a single center. The primary outcome was reintervention to treat postoperative stenosis. The secondary outcome was "catch-up" growth (faster diameter growth of the affected PA compared with the unaffected PA from the preoperative to follow-up measurements.). Twenty-six patients were identified with a total follow-up of 102.2 patient-years (median 2.5 years). Diagnoses included LPA sling (n = 12) and isolated PA of ductal origin with (n = 7) or without (n = 7) tetralogy of Fallot (ToF). All had primary repair of the anomalous PA. Seventeen (65%) had reintervention with median time to first reintervention of 69 (range 1-1005) days and median of 1.5 (range 1-6) reinterventions. 94% of reinterventions were transcatheter (53% balloon and 41% stent angioplasty). Patients with reintervention were younger (hazard ratio 0.75 per log-day, p = 0.02) and lower weight (hazard ratio 0.18 per log-kg, p = 0.02) at initial repair. Of the 18 with PA growth data, 8 (44%) had catch-up growth. There were no identified differences between those who did and did not demonstrate catch-up growth. Despite a practice of primary reimplantation and aggressive postoperative reintervention, these results suggest that changes in strategy are needed or that there are intrinsic patient factors that have more influence on longer-term reimplanted PA growth.

Surgical and Catheter-Based Reinterventions Are Common in Long-Term Survivors of the Fontan Operation.

BACKGROUND: There are limited follow-up studies examining surgical and catheter-based reinterventions in long-term survivors of the Fontan operation. METHODS AND RESULTS: All 773 patients who underwent Fontan at our institution between 1992 and 2009 were retrospectively reviewed. Current information regarding post-Fontan intervention was available for 70%. By 20 years after Fontan, 65% of patients had experienced either surgical or transcatheter intervention. The median time to first reintervention was 9.8 years. Freedom from reoperation was 69% at 15 years and 63% at 20 years. The most common operations were pacemaker placement and Fontan revision. Risk factors for pacemaker placement included systemic left ventricle (hazard ratio [HR], 2.2; P=0.006) and lateral tunnel Fontan (HR, 4.3; P=0.001). Freedom from interventional catheterization was 53% at 15 years and 50% at 20 years. The most common procedures performed were fenestration closure and pulmonary artery intervention. Catheter intervention for anatomic indications was associated with Fontan after 2002 (HR, 2.1; P=0.007), Norwood operation (HR, 2.3; P=0.001), and longer cardiopulmonary bypass time (HR, 1.1 per 10 minutes; P=0.001). Catheter intervention for physiological indications was associated with prolonged post-Fontan pleural drainage (HR, 4.0; P<0.001) and hypoplastic left heart syndrome (HR, 2.0; P=0.01). CONCLUSIONS: In this study of Fontan survivors, two thirds of patients required surgical or catheter-based reintervention by 20 years. Families should be counseled that the Fontan is typically not the final stage of single-ventricle palliation.

Long-term survival after the Fontan operation: Twenty years of experience at a single center.

OBJECTIVE: Existing studies of patients palliated with the Fontan operation are limited by heterogeneous patient populations and incomplete follow-up. This study aimed to describe long-term post-Fontan survival in a modern patient cohort. METHODS: All 773 patients who underwent a first Fontan operation at our institution between 1992 and 2009 were reviewed. The primary outcome was the composite endpoint of Fontan takedown, heart transplantation, or death before 2013. RESULTS: Follow-up rate was 99.2%. Survival with intact Fontan circulation was 94% at 1 year (95% confidence interval [95% CI], 92%-95%), 90% at 10 years (95% CI, 88%-92%), 85% at 15 years (95% CI, 82%-88%), and 74% at 20 years (95% CI, 67%-80%). Distinct risk factors were identified for early (≤1 year) and late composite outcomes. Independent risk factors for early outcome included prolonged pleural drainage (hazard ratio [HR], 4.4; P < .001), intensive care unit stay >1 week (HR, 2.4; P < .001), Fontan before 1997 (HR, 3.3; P < .001), preoperative atrioventricular valve regurgitation (HR, 2.0; P < .001), and longer crossclamp time (HR, 1.3 per 10 minutes; P < .001). Late outcome was predicted by atrioventricular valve regurgitation prior to Fontan (HR, 2.0; P ≤ .001), and post-Fontan ICU stay >1 week (HR, 2.4; P < .001). CONCLUSIONS: Long-term mortality after Fontan operation remains substantial. Risk factors for death or loss of Fontan circulation differ between the early and late postoperative periods. Long-term survival has not improved appreciably over the last decade, suggesting that alternatives to the Fontan are warranted.

Cumulative medical radiation exposure throughout staged palliation of single ventricle congenital heart disease.

Patients with single ventricle heart disease undergoing staged palliation are exposed to ionizing radiation from multiple medical sources. We sought to quantify typical radiation burden in this population and identify risk factors for increased exposure. A retrospective review was performed of single ventricle patients surgically palliated at our institution, in which all studies utilizing ionizing radiation occurring from birth through Fontan completion were compiled. Thirty-eight patients were followed for a median of 33 months. A median of 59 radiation events occurred during follow-up, with a median cumulative effective dose of 25.7 milliSieverts (mSv). On average, cardiac catheterization accounted for 4% of radiation encounters but comprised 78% of total radiation exposure. In a multivariate model, factors associated with increased total radiation exposure included pulmonary artery (PA) stenosis requiring intervention (p = 0.005) and systemic right ventricle (p = 0.02). Risk factors for increased exposure from catheterization included heterotaxy syndrome (p = 0.007), re-coarctation (p = 0.003), and PA stenosis (p = 0.02). At our institution, many single ventricle patients are exposed to substantial radiation throughout staged palliation, most of which derives from cardiac catheterization. PA stenosis was identified as a risk factor for increased total and catheterization-based exposure. As patient survival improves, awareness of this scale of radiation exposure at a vulnerable period is imperative.

Cumulative exposure to medical sources of ionizing radiation in the first year after pediatric heart transplantation.

BACKGROUND: Pediatric heart transplant recipients undergo a variety of radiologic tests with the attendant risk of exposure to ionizing radiation. We sought to quantify and describe the cumulative exposure to all forms of medical radiation during the first year after pediatric heart transplantation and identify factors associated with higher exposure. METHODS: Pediatric patients who received a heart transplant between January 2009 and May 2012 with follow-up at our institution were retrospectively reviewed. Patients were included if they survived through 1 year and the first coronary angiography. All medical testing using ionizing radiation performed during follow-up was compiled, and exposures were converted to effective dose (mSv). RESULTS: Included were 31 patients who underwent heart transplantation at a median age of 13.6 years (range, 0.3-18.3 years). The median number of radiologic tests performed was 38 (range, 18-154), including 8 catheterizations (range, 2-12), and 28 X-ray images (range, 11-135). Median cumulative effective dose was 53.5 mSv (range, 10.6-153.5 mSv), of which 91% (range, 34%-98%) derived from catheterizations, 31% (range, 8%-89%) of the exposure occurred during the transplant admission, 59% (range, 11%-88%) during planned follow-up, and 3% (0%-56%) during unplanned follow-up. Older age at transplant was a risk factor for increased exposure (p = 0.006). When adjusted for age, a trend toward increased exposure was shown for congenital heart disease as the indication for transplant (p = 0.08), pre-sensitization (p = 0.12), and positive crossmatch (p = 0.09). CONCLUSIONS: Pediatric heart transplant patients are exposed to significant amounts of ionizing radiation during the first post-transplant year, most during scheduled catheterization. As survival improves, considering the long-term risks associated with these levels of exposure is important.

Pulmonary histopathology in an experimental model of chronic aspiration is independent of acidity.

Gastroesophageal reflux has become a major health concern in industrialized countries, with drugs aimed at blocking acid production being more frequently prescribed than any other drug. Damage to lung tissue as a result of chronic aspiration of gastric fluid is a primary health risk associated with gastro-esophageal reflux, with such aspiration being suspected in the induction or exacerbation of asthma and other lung diseases. In this study, a rodent model of chronic aspiration was used to characterize the pulmonary histopathology produced by repetitive aspiration events and to investigate the pathologic roles of individual gastric fluid components such as acid and particulate food matter. Rats exposed to chronic aspiration of whole gastric fluid developed a pathology distinct from that of acute lung injury, characterized by granulomatous interstitial pneumonitis with prominent formation of multinucleated giant cells. This pattern of injury could be reproduced with chronic aspiration of particulate food matter and with chronic aspiration of pH-neutralized gastric fluid, but not with chronic aspiration of hydrochloric acid. Thus, since acid-neutralizing therapy is currently the mainstay of treatment for patients with reflux-associated respiratory symptoms, these results strongly suggest that alternative therapeutic approaches aimed at preventing chronic-aspiration induced lung injury may be warranted.