Management of pulmonary vascular disease associated with congenital left-to-right shunts: A single-center experience.

OBJECTIVE: The study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First). METHODS: We performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m2) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed. RESULTS: Of 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m2). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77). CONCLUSIONS: In children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension-targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients.

A single institution anesthetic experience with catheterization of pediatric pulmonary hypertension patients.

Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway. Median age was 3.4 years (interquartile range [IQR] 0.7-9.7); the majority were either Nice Classification Group 1 (48%) or Group 3 (42%). Vasoactive medications and cardiopulmonary resuscitation were required in 14 (3.7%) and eight (2.1%) cases, respectively; there was one death. Characteristics associated with use of an invasive airway included age <1 year, Group 3, congenital heart disease, trisomy 21, prematurity, bronchopulmonary dysplasia, WHO functional class III/IV, no PH therapy at time of case, preoperative respiratory support, and having had an intervention (p < 0.05). A composite predictor of age <1 year, Group 3, prematurity, and any preoperative respiratory support was significantly associated with unplanned airway escalation (26.7% vs. 6.9%, odds ratio: 4.9, confidence interval: 1.4-17.0). This approach appears safe, with serious adverse event rates similar to previous reports despite the predominant use of natural airways. However, research is needed to further investigate the optimal anesthetic regimen and respiratory support for pediatric PH patients undergoing cardiac catheterization.

Differences in Quality of Life in Children Across the Spectrum of Congenital Heart Disease.

OBJECTIVE: To create complexity groups based upon a patient's cardiac medical history and to test for group differences in health-related quality of life (HRQOL). METHODS: Patients 8-18 years with congenital heart disease (CHD) and parent-proxies from the Pediatric Cardiac Quality of Life Inventory (PCQLI) Testing Study were included. Outcome variables included PCQLI Total, Disease Impact, and Psychosocial Impact scores. Using a patient's medical history (cardiac, neurologic, psychological, and cognitive diagnosis), latent class analysis (LCA) was used to create CHD complexity groups. Covariates included demographics and burden of illness (number of: school weeks missed, physician visits in the past year, and daily medications). Generalized estimation equations tested for differences in burden of illness and patient and parent-proxy PCQLI scores. RESULTS: Using 1482 CHD patients (60% male; 84% white; age 12.3 ± 3.0 years), latent class analysis (LCA) estimates showed 4 distinct CHD complexity groups (Mild, Moderate 1, Moderate 2, and Severe). Increasing CHD complexity was associated with increased risk of learning disorders, seizures, mental health problems, and history of stroke. Greater CHD complexity was associated with greater burden of illness (P < .01) and lower patient- and parent-reported PCQLI scores (P < .001). CONCLUSIONS: LCA identified 4 congenital heart disease (CHD) complexity groupings. Increasing CHD complexity was associated with higher burden of illness and worse patient- and parent-reported HRQOL.

Persistence of persistent pulmonary hypertension of the newborn: A case of de novo TBX4 variant.

We present a case of a late preterm infant placed on extracorporeal life support in the first day of life for persistent pulmonary hypertension of the newborn. Developmental arrest, pulmonary vascular hypertensive changes, and pulmonary interstitial glycogenosis were present on lung biopsy at 7 weeks of age. Pulmonary hypertension has persisted through childhood. Genetic testing at 8 years identified a novel mutation in TBX4.

Pulmonary artery acceleration time in young children is determined by heart rate and transpulmonary gradient but not by pulmonary blood flow: A simultaneous echocardiography-cardiac catheterization study.

INTRODUCTION: Pulmonary artery acceleration time (PAAT) is considered useful for the non-invasive evaluation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). PAAT is dependent on PAP, PVR, pulmonary artery compliance, stroke volume, and heart rate. Its relative dependency on these determinants may differ between young and older children, raising uncertainty regarding its utility in young children. We aim to identify the primary determinants of the PAAT in children less than 36 months undergoing cardiac catheterization and its utility for the diagnosis of elevated PVR. METHODS: We prospectively studied 42 children undergoing cardiac catheterization and simultaneous echocardiography. We determined the correlations of PAAT to the above-mentioned determinants and evaluated receiver operator characteristic (ROC) curves for diagnosis of PVR indexed to body surface area (PVRi) ≥3 Wu*m2 . RESULTS: Median age was 11.5 (IQR 5.2, 21.2) months. Moderate correlations were found between PAAT and mean PAP (R = -.66, p < .001), PVRi (R = -.54, p = .004), pulmonary artery compliance (R = .65, p < .001), transpulmonary gradient (R = -.67, p < .001), stroke volume (R = .61, p = .002), and heart rate (R = -.63, p < .001). In multivariate regression modeling, only transpulmonary gradient and heart rate were independent determinants of PAAT. PAAT ≤77 msec had acceptable utility for diagnosing PVRi ≥ 3 Wu*m2 (AUC .8 [.64, .95], n = 36), low sensitivity (59%), and excellent specificity (94%). CONCLUSION: Transpulmonary gradient and heart rate, but not pulmonary blood flow, are important determinants of PAAT in children <36 months undergoing cardiac catheterization. PAAT has low sensitivity for diagnosing elevated PVRi, therefore, should not be solely relied upon in screening for elevated PVRi in young children.

Genetics dictating therapeutic decisions in pediatric pulmonary hypertension? A case report suggesting we are getting closer.

Despite therapeutic advances over the past decades, pulmonary arterial hypertension (PAH) and related pulmonary vascular diseases continue to cause significant morbidity and mortality in neonates, infants, and children. Unfortunately, an adequate understanding of underlying biology is lacking. There has been a growing interest in the role that genetic factors influence pulmonary vascular disease, with the hope that genetic information may aid in identifying disease etiologies, guide therapeutic decisions, and ultimately identify novel therapeutic targets. In fact, current data suggest that genetic factors contribute to ~42% of pediatric-onset PH compared to ~12.5% of adult-onset PAH. We report a case in which the knowledge that biallelic ATP13A3 mutations are associated with malignant progression of PAH in young childhood, led us to alter our traditional treatment plan for a 21-month-old PAH patient. In this case, we elected to perform a historically high-risk Potts shunt before expected rapid deterioration. Short-term follow-up is encouraging, and the patient remains the only known surviving pediatric PAH patient with an associated biallelic ATP13A3 mutation in the literature. We speculate that an increased use of comprehensive genetic testing can aid in identifying the underlying pathobiology and the expected natural history, and guide treatment plans among PAH patients.

Doppler Echocardiographic Features of Pulmonary Vein Stenosis in Ex-Preterm Children.

BACKGROUND: Echocardiography is used to screen for the presence of pulmonary vein stenosis (PVS) in ex-preterm infants and children. However, there are no standard accepted criteria for screening or diagnosis of PVS by echocardiography. The aim of this study was to identify Doppler waveform features and Doppler systolic and diastolic velocity cutoff values associated with a diagnosis of PVS by cardiac catheterization. METHODS: In this retrospective observational study, the echocardiograms of ex-preterm children <3 years old who underwent cardiac catheterization at a single institution were reviewed. PVS on cardiac catheterization was defined by a mean pressure gradient of >3 mm Hg in the pulmonary vein, with angiographic evidence of stenosis. Pulmonary vein Doppler waveforms, from echocardiograms obtained before catheterization, in children with and without PVS were compared. Nonstenosed veins in patients with PVS were excluded. The systolic and diastolic velocities of blood flow, phasic flow, and return of the Doppler waveform to baseline were analyzed. RESULTS: Forty-seven children were analyzed in the study, 18 children with 25 stenosed pulmonary veins and 29 children with 78 nonstenosed pulmonary veins. Stenosed pulmonary veins had higher peak systolic and diastolic velocities and higher peak and mean pressure gradients as measured by spectral Doppler. Peak systolic and diastolic velocities had areas under the receiver operating characteristic curve of 0.89 (95% CI, 0.79-0.99) and 0.93 (95% CI, 0.85-0.99) for PVS, respectively, and a threshold velocity of 0.7 m/sec had sensitivity of 80% and 84% and specificity of 94%. There was no correlation between Doppler-derived pulmonary vein mean gradient and measured pulmonary vein mean gradient during cardiac catheterization in stenosed pulmonary veins. Presence of phasic flow in the pulmonary vein and return of the Doppler waveform to baseline were associated with a nonstenosed pulmonary vein (sensitivity of 94% and 60% and specificity of 52% and 60%, respectively). CONCLUSIONS: Systolic and diastolic Doppler velocities and features of the waveform can discriminate stenosed pulmonary veins confirmed by cardiac catheterization in ex-preterm children. These results suggest the use of lower systolic and diastolic Doppler velocity cutoff values than currently published to screen for PVS in ex-preterm children. These cutoff values require validation in prospective studies.

Clinical Utility of Echocardiography in Former Preterm Infants with Bronchopulmonary Dysplasia.

BACKGROUND: The clinical utility of echocardiography for the diagnosis of pulmonary vascular disease (PVD) in former preterm infants with bronchopulmonary dysplasia (BPD) is not established. Elevated pulmonary vascular resistance (PVR) rather than pulmonary artery pressure (PAP) is the hallmark of PVD. We evaluated the utility of echocardiography in infants with BPD in diagnosing pulmonary hypertension and PVD (PVR >3 Wood units × m2) assessed by cardiac catheterization. METHODS: A retrospective single center study of 29 infants born ≤29 weeks of gestational age with BPD who underwent cardiac catheterization and echocardiography was performed. PVD was considered present by echocardiography if the tricuspid valve regurgitation jet peak velocity was >2.9 m/sec, post-tricuspid valve shunt systolic flow velocity estimated a right ventricular systolic pressure >35 mm Hg, or systolic septal flattening was present. The utility (accuracy, sensitivity, and positive predictive value [PPV]) of echocardiography in the diagnosis of PVD was tested. Subgroup analysis in patients without post-tricuspid valve shunts was performed. Echocardiographic estimations of right ventricular pressure, dimensions, function, and pulmonary flow measurements were evaluated for correlation with PVR. RESULTS: The duration between echocardiography and cardiac catheterization was a median of 1 day (interquartile range, 1-4 days). Accuracy, sensitivity, and PPV of echocardiography in diagnosing PVD were 72%, 90.5%, and 76%, respectively. Accuracy, sensitivity, and PPV increased to 93%, 91.7%, and 100%, respectively, when infants with post-tricuspid valve shunts were excluded. Echocardiography had poor accuracy in estimating the degree of PAP elevation by cardiac catheterization. In infants without post-tricuspid valve shunts, there was moderate to good correlation between indexed PVR and right ventricular myocardial performance index (rho = 0.89, P = .005), systolic to diastolic time index (0.84, P < .001), right to left ventricular diameter ratio at end systole (0.66, P = .003), and pulmonary artery acceleration time (0.48, P = .05). CONCLUSIONS: Echocardiography performs well in screening for PVD in infants with BPD and may be diagnostic in the absence of a post-tricuspid valve shunt. However, cardiac catheterization is needed to assess the degree of PAP elevation and PVR. The diagnostic utility of echocardiographic measurements that correlate with PVR should be evaluated prospectively in this patient population.

Development and Utility of Quality Metrics for Ambulatory Pediatric Cardiology in Kawasaki Disease.

The Adult Congenital and Pediatric Cardiology (ACPC) Section of the American College of Cardiology sought to develop quality indicators/metrics for ambulatory pediatric cardiology practice. The objective of this study was to report the creation of metrics for patients with Kawasaki disease. Over a period of 5 months, 12 pediatric cardiologists developed 24 quality metrics based on the most relevant statements, guidelines, and research studies pertaining to Kawasaki disease. Of the 24 metrics, the 8 metrics deemed the most important, feasible, and valid were sent on to the ACPC for consideration. Seven of the 8 metrics were approved using the RAND method by an expert panel. All 7 metrics approved by the ACPC council were accepted by ACPC membership after an "open comments" process. They have been disseminated to the pediatric cardiology community for implementation by the ACPC Quality Network.

Mortality in infants with bronchopulmonary dysplasia: Data from cardiac catheterization.

RATIONALE: Pulmonary hypertension (PH) is relatively common in infants with severe bronchopulmonary dysplasia (BPD), however, hemodynamic data and factors associated with mortality in this patient group are sparsely described in the literature. OBJECTIVES: To characterize the hemodynamics of former preterm infants with BPD and PH, as measured at cardiac catheterization, and to identify respiratory and cardiovascular predictors of mortality. METHODS: Single-center, retrospective cohort study, including, 30 patients born at less than 32-week gestational age (GA), who had an oxygen requirement at 36 weeks postmenstrual age and underwent cardiac catheterization between July 2014 and December 2017. RESULTS: Median GA at birth was 25 5/7 weeks (interquartile range [IQR], 24 4/7-26 6/7 weeks). Median birth weight was 620 g (IQR, 530-700 g). With a median of 23 months of follow up (IQR, 11-39 months), mortality as of July 2018 was 27% (8 of 30). The alveolar-arterial oxygen gradient as a measure of lung disease did not correlate with mortality (log-rank test P = 0.28). However, indexed pulmonary vascular resistance (PVR) of greater than 3 Woods units × m 2 showed a trend toward increased mortality (log-rank test P = 0.12). Pulmonary vein stenosis was the only predictor significantly associated with mortality (log-rank test P = 0.005). CONCLUSIONS: In this cohort, the severity of lung disease as assessed by impaired oxygenation at cardiac catheterization did not correlate with mortality. The only factor significantly associated with mortality was the presence of pulmonary vein stenosis on cardiac catheterization, although PVR may also be an important factor.

"There's no acknowledgement of what this does to people": A qualitative exploration of mental health among parents of children with critical congenital heart defects.

AIMS AND OBJECTIVES: The purpose of this study was to explore the psychological impact of parenting a child with a critical congenital heart defect and the feasibility and acceptability of integrating psychological services into paediatric cardiology care. BACKGROUND: Children with critical congenital heart defect are at an increased risk for long-term behavioural, social and emotional difficulties. Data suggest that this risk is partially attributable to parental mental health, which is a stronger predictor of long-term behavioural problems in congenital heart defect children than disease-specific and surgical factors. Parental stress and mental health are thus important intervention targets, especially among high-risk families. DESIGN: This article presents data from a qualitative study with 25 congenital heart defect parents (n = 15) and providers (n = 10). METHODS: Using thematic analysis, semi-structured in-depth interviews were transcribed and coded by the first and second author to identify major themes and subthemes. RESULTS: Results of the interviews were organised into four major themes: (i) the psychological impact of parenting a child with critical congenital heart defect, (ii) factors that influence the psychological impact of parenting a child with critical congenital heart defect, (iii) how and when to psychologically support congenital heart defect parents and (iv) feasibility and acceptability of integrating psychological support into congenital heart defect care. Providers and parents endorsed the integration of mental health treatment into routine congenital heart defect care and identified several practical issues related to feasibility (e.g., funding and space) that should be considered prior to implementation. CONCLUSIONS: Parents of children with critical congenital heart defect need access to mental health services, and integrating these services into routine paediatric cardiology care is a novel and practical way for parents to receive the treatment they need. RELEVANCE TO CLINICAL PRACTICE: Suggestions for how the field of paediatric cardiology could begin to integrate mental health services into congenital heart defect treatment are provided.

Pushing the envelope: a treat and repair strategy for patients with advanced pulmonary hypertension associated with congenital heart disease.

Pulmonary arterial hypertension (PAH) is a frequent complication of congenital heart disease as a consequence of altered pulmonary hemodynamics with increased pulmonary blood flow and pressure. The development of pulmonary vascular disease (PVD) in this patient population is an important concern in determining operative strategy. Early, definitive surgical repair, when possible, is the best therapy to prevent and treat PVD. However, this is not possible in some patients because they either presented late, after the development of PVD, or they have complex lesions not amenable to one-step surgical correction, including patients with single ventricle physiology, who have a continuing risk of developing PVD. These patients represent an important, high-risk subgroup and many have been considered inoperable. We present a case series of two patients with complex congenital heart disease and advanced PVD who successfully underwent a treat and repair strategy with aggressive PAH therapies before surgical correction. Both patients had normalization of pulmonary vascular resistance prior to surgical correction. Caution is warranted in applying this strategy broadly and long-term follow-up for these patients is crucial. However, this treat and repair strategy may allow for favorable outcomes among some patients who previously had no therapeutic options.

Mental Health Among Parents of Children With Critical Congenital Heart Defects: A Systematic Review.

BACKGROUND: Parents of children with critical congenital heart defects (PCCHDs) may be at high risk for mental health morbidity; however, the literature is not well characterized. Given that compromised parental mental health can lead to long-term cognitive, health-related, and behavioral problems in children, a systematic review of this literature could provide informed recommendations for continued research and enhance the care of families of children living with critical congenital heart defects. METHODS AND RESULTS: We conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that resulted in 30 studies on the mental health of PCCHDs. The literature revealed that PCCHDs are at an elevated risk for psychological problems, particularly in the immediate weeks and months following cardiac surgery. Up to 30% of PCCHDs have symptoms consistent with a diagnosis of posttraumatic stress disorder, with over 80% presenting with clinically significant symptoms of trauma; 25% to 50% of PCCHDs reported clinically elevated symptoms of depression and/or anxiety, and 30% to 80% reported experiencing severe psychological distress. There was high variability in measurements used to assess study outcomes, methodological quality, and sociocultural composition of the parents included in the studies. CONCLUSIONS: There is an urgent need for additional research on the severity, course, persistence, and moderators of these mental health problems over time, and for the development and testing of screening approaches and interventions that can be feasibly delivered in the context of ongoing pediatric cardiac care.

Development of Quality Metrics in Ambulatory Pediatric Cardiology.

The American College of Cardiology Adult Congenital and Pediatric Cardiology (ACPC) Section had attempted to create quality metrics (QM) for ambulatory pediatric practice, but limited evidence made the process difficult. The ACPC sought to develop QMs for ambulatory pediatric cardiology practice. Five areas of interest were identified, and QMs were developed in a 2-step review process. In the first step, an expert panel, using the modified RAND-UCLA methodology, rated each QM for feasibility and validity. The second step sought input from ACPC Section members; final approval was by a vote of the ACPC Council. Work groups proposed a total of 44 QMs. Thirty-one metrics passed the RAND process and, after the open comment period, the ACPC council approved 18 metrics. The project resulted in successful development of QMs in ambulatory pediatric cardiology for a range of ambulatory domains.

Recognition of Undiagnosed Neonatal Heart Disease.

Heart defects are the most common congenital malformation. Approximately 8000 infants per year in the United States require diagnosis in the newborn period to avoid severe injury or death. It is incumbent on the neonatologist and pediatrician to expeditiously detect the presence of symptomatic heart disease so that infants can be stabilized before cardiovascular decompensation. Evaluating infants and further categorizing them into the particular pathophysiology are necessary to stabilize them in anticipation of more definitive care by the pediatric cardiac team.

Use and performance of premounted stents compared to nonpremounted stents in pediatric and adult congenital cardiac catheterization.

OBJECTIVES: We sought to characterize the use, efficacy, and performance characteristics of premounted stents relative to nonpremounted stents when used during congenital cardiac catheterization. BACKGROUND: Endovascular stent implantation is an effective means of relieving vascular obstruction in patients with congenital heart disease. However, stent implantation is technically challenging and important complications occur. Premounted stents appear to offer many advantages relative to their nonpremounted counterparts, and it has been suggested that the use of premounted stents is associated with fewer complications. However, translation of these potential benefits into procedural or clinical success has been poorly examined and the data are conflicting. METHODS: All stent placements performed between January 1, 1999 and December 31, 2009 were reviewed. Analysis of technical success, hemodynamic success and complications was performed. RESULTS: 416 stents were placed over the 10 year period. 158 (38%) were premounted. There was no apparent trend in the frequency of use of premounted stents over the study period. Implanted premounted stents were smaller in diameter than nonpremounted stents 4.9 mm +/- 1.8 versus 13.9 mm +/- 3.7, and the site of stent placement differed significantly. Unadjusted and adjusted analysis of technical success with respect to the precision of stent placement, hemodynamic success, and complications showed no difference between premounted and non-premounted stents. CONCLUSIONS: We found no difference between premounted and nonpremounted stents with respect to procedural and hemodynamic success or complications. Nevertheless, there remain practical advantages to the use of premounted stents that may justify their expanding role in congenital cardiac catheterization.