1. The risk of cardiac arrest after a cardiac catheterization in patients with pulmonary hypertension (PH) is much higher in children compared to adults; what do [you] believe is the explanation for this finding?

Our study¹ did not directly compare outcomes following cardiac catheterization between adults and children with pulmonary hypertension (PH). However, the observed rate of catastrophic adverse outcome was higher than that observed in other studies of catheterization in adults with PH.² Explanations could arise from the design of our study, differences in our study population from prior studies, or from intrinsic differences between children and adults with PH.

Firstly, The Pediatric Health Information Systems (PHIS) database includes all inpatient and observation admissions from 43 primary pediatric hospitals in the United States (US), which specifically avoids bias introduced in prospective clinical registries that require consent (which may over-represent patients with less severe disease) and produces a cohort with superior generalizability to practice in the US. The cohort also contains a broader range of patients (in terms of etiology of PH and comorbid conditions) and hospitals (in terms of size and experience with PH).

The study was not designed to identify factors that placed children at greater risk than adults, limiting what we can infer from the data; however, younger age was associated with higher risk even within a pediatric study population, supporting an overall relationship between age and risk. Confounding by indication may be present if younger age at catheterization was also associated with a higher risk of severe disease. Unfortunately, hemodynamic and clinical data are limited in PHIS, so this cannot be assessed directly. Diagnostic right heart catheterization is not technically difficult regardless of patient size, but it may be possible that technical issues influence this association. Procedural recovery from sedation and anesthesia is a period of vulnerability in patients with PH. This risk may be higher in children. Cardiac catheterization in children is most often performed with general anesthesia, in contrast to diagnostic catheterization in adults which is often performed without anesthesia. Additionally, the immature airway and increased need for pharmacotherapy to maintain calm during flat time and procedural recovery, could influence risk of recovery from anesthesia in children with PH. This deserves further study, as optimizing post-procedure recovery is a potentially modifiable risk factor influencing safety of heart catheterization in children with PH.

2. What factors are associated with worse outcomes in children with PH undergoing cardiac catheterization? What factors are associated with better outcomes?

In our study, there were several patient-level factors that were associated with elevated risk. As noted above, younger age and prematurity were associated with increased risk. Idiopathic pulmonary arterial hypertension (IPAH) subjects were at lower risk than patients with PH after heart transplantation, and suggestive but not significant associations with increased risk were seen in with PH and either concomitant congenital heart disease or cardiomyopathy. A cardiac operation during the same admission, receipt of renal replacement therapy, and afterload reducing agents all were associated with increased risk of catastrophic outcome.

Procedural volume by center also influenced risk, with the risk at the lowest two quintiles of procedural volume significantly higher than the top three quintiles. This finding supports the previous observation that increased hospital catheterization volume was protective across the broad range of transcatheter procedures in children.³ Whether this suggests that there are intrinsic benefits to larger volume programs, or whether the benefit of larger volume programs arises from "best practices,' which might be transmissible to programs of all sizes, is a question that deserves continued attention.

Recent published guidelines recommend right heart catheterization and pulmonary vasodilator challenge to guide initiation of therapy in children with PAH.^4-6 As with all procedures, the risk: benefit ratio should be considered when considering right heart catheterization.

3. Is there any correlation between severity of hemodynamic findings and outcomes (i.e. pulmonary vascular resistance, cardiac output, etc.)?

A major limitation of our data source is that it is an administrative database (with data extracted from billing records) without hemodynamic data. Other studies showed elevated pulmonary vascular resistance (PVR) of pulmonary artery pressure as risk factors.^7-9; however, these have not assessed for a dose response in either case. For risk adjustment, a study including both clinical and hemodynamic from a large number of centers would be necessary.

However, to improve outcomes in children with PH, development of a validated prediction rule based on data that is available prior to catheterization (excluding hemodynamics which are not available prior to the procedure) would be an important step forward. This would improve pre-procedural risk stratification and improve decision-making regarding the relative risks and benefits of hemodynamic at the individual patient level. Continued study of the determinants of the risk of hemodynamic evaluation in this population potentially will allow us to identify modifiable and non-modifiable risk factors for catastrophic outcome. These would enable us to consider interventions to improve the care of children with PH.

References

1. O'Byrne ML, Glatz AC, Hanna BD, et al. Predictors of Catastrophic Adverse Outcomes in Children With Pulmonary Hypertension Undergoing Cardiac Catheterization: A Multi-Institutional Analysis From the Pediatric Health Information Systems Database. J Am Coll Cardiol 2015;66:1261–9.
2. Hoeper MM, Lee SH, Voswinckel R, et al. Complications of right heart catheterization procedures in patients with pulmonary hypertension in experienced centers. J Am Coll Cardiol 2006;48:2546–52.
3. O'Byrne ML, Glatz AC, Shinohara RT, et al. Effect of center catheterization volume on risk of catastrophic adverse event after cardiac catheterization in children. Am Heart J 2015;169:823–32.e5.
4. Abman SH, Hansmann G, Archer SL, et al. Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society. Circulation 2015;132:2037–99.
5. Simonneau G, Galiè N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004;43:S5–S12.
6. Galiè N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004;25:2243–78.
7. Bergersen L, Gauvreau K, Foerster SR, et al. Catheterization for Congenital Heart Disease Adjustment for Risk Method (CHARM). JACC Cardiovasc Interv 2011;4:1037–46.
8. Nykanen DG, Forbes TJ, Du W, et al. CRISP: Catheterization RISk score for pediatrics: A Report from the Congenital Cardiac Interventional Study Consortium (CCISC). Cathet Cardiovasc Intervent 2016;87:302-9.
9. Jayaram N, Beekman RH, Benson L, et al. Adjusting for Risk Associated With Pediatric and Congenital Cardiac Catheterization: A Report From the NCDR IMPACT Registry. Circulation 2015;132:1863–70.

Keywords: Anesthesia, General, Cardiac Catheterization, Cardiac Output, Cardiomyopathies, Child, Hypertension, Pulmonary, Heart Arrest, Heart Diseases, Heart Transplantation, Hospitals, Pediatric, Inpatients, Pulmonary Artery, Reducing Agents, Renal Replacement Therapy, Risk Adjustment, Risk Factors, Vascular Resistance, Vasodilator Agents

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