Predictors of Operability in Children with Severe Pulmonary Hypertension Associated with Congenital Heart Disease
Pulmonary arterial hypertension (PAH) associated with congenital heart disease (PAH-CHD) is a severe and often fatal condition characterized by progressive pulmonary vascular remodeling, elevated vascular resistance, heart failure, and death if left untreated. PAH-CHD is particularly prevalent in patients with uncorrected congenital heart defects, where abnormal hemodynamics, such as left-to-right shunts, lead to increased pulmonary blood flow and pressure. This condition is the second most common type of PAH in children, accounting for over 40% of cases, and is even more prevalent in developing regions. Despite advances in medical therapy, the management of severe pediatric PAH-CHD remains challenging, and surgical correction of the underlying congenital heart defect is often necessary. However, the decision to operate and the prognosis of surgical intervention are complex and require careful evaluation of predictors of operability.
This study aimed to identify predictors of operability and prognosis in children with severe PAH-CHD who underwent surgical correction. The research was conducted at the Guangdong Provincial People’s Hospital in China, where data from 59 children with severe PAH-CHD who underwent surgical correction between May 2011 and June 2015 were retrospectively analyzed. The study focused on evaluating the role of hemodynamic parameters, particularly pulmonary vascular resistance (PVR) and the PVR/systemic vascular resistance (SVR) ratio, in predicting surgical outcomes. The findings provide valuable insights into the management of severe pediatric PAH-CHD and offer evidence-based recommendations for surgical intervention.
Background and Significance
PAH-CHD is a devastating condition that arises from abnormal hemodynamics caused by congenital heart defects. The persistent left-to-right shunt leads to increased pulmonary blood flow, which, over time, results in pulmonary vascular remodeling, elevated pulmonary vascular resistance, and eventually right heart failure. Surgical correction of the congenital heart defect is the most effective treatment for PAH-CHD, as it eliminates the abnormal shunt and reduces pulmonary pressure. However, the decision to operate is complicated by the risk of persistent or worsening pulmonary hypertension after surgery, which can lead to poor outcomes or even death.
Current guidelines recommend surgical repair for PAH-CHD patients with a pulmonary vascular resistance index (PVRI) less than 6 Wood units (WU)/m² or a PVR/SVR ratio less than 0.3 during an acute vasoreactivity test (AVT). However, there is a “gray area” for patients with PVRI between 6 and 10 WU/m² or a PVR/SVR ratio between 0.3 and 0.5, where the decision to operate is less clear. This study sought to address this gap by identifying specific hemodynamic predictors that could guide surgical decision-making in children with severe PAH-CHD.
Study Design and Methods
The study included 59 children aged 2 to 18 years with severe PAH-CHD (defined as pulmonary artery systolic pressure [PASP] ≥70 mmHg) who underwent surgical correction at the Guangdong Provincial People’s Hospital. The patients were followed for a median observation period of 49±20 months, with data collected retrospectively from medical records. The study protocol was approved by the Institutional Review Board of the hospital, and all procedures were conducted in accordance with the Declaration of Helsinki.
All patients underwent heart catheterization and an acute vasoreactivity test (AVT) using inhaled iloprost, a prostacyclin analog. The AVT was performed to assess the vasodilatory capacity of the pulmonary vasculature. Hemodynamic parameters, including PVR, PVR/SVR ratio, and mean pulmonary artery pressure (mPAP), were measured before and after iloprost inhalation. Surgical correction was performed if the PVRI was less than 6 WU/m² or the PVR/SVR ratio was less than 0.3 during the AVT. For patients with higher PVRI or PVR/SVR ratios, a modified surgical approach with a residual atrial or ventricular septal defect was considered.
Postoperative management included the use of specific PAH-targeting drugs, such as bosentan, sildenafil, and treprostinil, as well as diuretics and digoxin, based on the patient’s condition. The patients were followed up regularly, with assessments of PASP, heart function, and exercise capacity using the 6-minute walk distance (6MWD) test. The outcomes were classified as favorable or unfavorable based on improvements in pulmonary pressure, heart function, and the need for continued PAH-specific therapy.
Results
The study included 56 children (26 males and 30 females) after excluding three patients lost to follow-up. The baseline characteristics of the patients are summarized in Table 1. The most common congenital heart defects were ventricular septal defect (VSD) (n=28), atrial septal defect (ASD) (n=5), and patent ductus arteriosus (PDA) (n=9). The patients were divided into two groups based on their outcomes: favorable (n=42) and unfavorable (n=14).
The results showed significant improvements in pulmonary pressure and heart function after surgical correction. The PASP decreased from a median of 93 mmHg at baseline to 30 mmHg two years after surgery (p<0.01). Heart function, as assessed by the New York Heart Association (NYHA) functional class, also improved significantly (p<0.05). In the favorable group, 42 patients (75%) successfully discontinued PAH-specific therapy, while 12 patients (29%) in the unfavorable group required continued treatment. Two patients (3.5%) died during the follow-up period, and one patient underwent a second thoracotomy to remove a ventricular septal defect patch.
The study identified PVRI and PVR/SVR ratio during the AVT as excellent predictors of surgical outcome. The receiver-operating characteristic (ROC) curve analysis showed that a PVRI less than 6.65 WU/m² or a PVR/SVR ratio less than 0.39 after iloprost inhalation predicted a favorable prognosis with high sensitivity (100%) and specificity (82.1% and 92.9%, respectively). The Kaplan-Meier survival analysis further confirmed that patients with a low PVR/SVR ratio (<0.39) had significantly better survival rates than those with a high ratio (p<0.05).
Discussion
The findings of this study highlight the importance of hemodynamic assessment in predicting the operability and prognosis of children with severe PAH-CHD. The results demonstrate that surgical correction, combined with postoperative PAH-specific therapy, is an effective strategy for managing severe PAH-CHD. The study also provides specific cut-off values for PVRI (6.65 WU/m²) and PVR/SVR ratio (0.39) during AVT, which can guide surgical decision-making in this challenging patient population.
The study’s results are consistent with previous research showing that pulmonary pressure and heart function improve significantly after surgical correction of congenital heart defects. However, the study also highlights the variability in outcomes among patients, with some experiencing persistent or worsening pulmonary hypertension despite surgical intervention. This underscores the need for careful patient selection and individualized treatment plans.
One of the key findings of the study is the limited efficacy of the currently used acute vasoreactivity criteria in pediatric PAH-CHD. The study found that the criteria defined by Ivy et al., Rich et al., and Barst et al. had low positive rates and specificity in predicting surgical outcomes. Instead, the study identified PVRI and PVR/SVR ratio during AVT as more reliable predictors of prognosis. These findings suggest that the current criteria for AVT responders may need to be revised for pediatric PAH-CHD patients.
The study also highlights the challenges of managing severe PAH-CHD in children, particularly in the “gray area” where the decision to operate is less clear. The results suggest that surgical intervention can be considered for patients with a PVRI less than 6.65 WU/m² or a PVR/SVR ratio less than 0.39 during AVT. However, the decision to operate should be made by an experienced medical team based on a thorough clinical evaluation and hemodynamic data.
Limitations
The study has several limitations. First, the retrospective design may introduce bias in data collection and analysis. Second, the sample size was relatively small, which may limit the generalizability of the findings. Third, the study did not investigate other potential factors that could affect surgical outcomes, such as genetic or environmental factors. Despite these limitations, the study provides valuable insights into the management of severe pediatric PAH-CHD and offers evidence-based recommendations for surgical intervention.
Conclusion
This study demonstrates that PVRI and PVR/SVR ratio during AVT are excellent predictors of outcome in children with severe PAH-CHD. Surgical correction, combined with postoperative PAH-specific therapy, is an effective strategy for managing this condition. The study provides specific cut-off values for PVRI (6.65 WU/m²) and PVR/SVR ratio (0.39) during AVT, which can guide surgical decision-making in this challenging patient population. However, the management of severe PAH-CHD remains complex and requires individualized treatment plans based on hemodynamic data and clinical evaluation. Further research is needed to validate these findings and improve the management of pediatric PAH-CHD.
doi.org/10.1097/CM9.0000000000000145
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