Syncope May Increase Vasoreactivity Among Pediatric Patients With PAH

Higher rates of vasoreactivity were seen among pediatric patients who had comorbid group 1 pulmonary arterial hypertension (PAH) and syncope—also known as fainting or passing out—indicating the latter condition may be the result of acute pulmonary vasoconstriction in this patient population.

The study findings were published recently online in European Respiratory Journal Open Research, and they encompassed the results of a retrospective chart review of children receiving care for PAH at Columbia University Medical Center between January 1, 2005, and October 31, 2018. Information was collected on symptoms, imaging hemodynamics, baseline and follow-up outcomes, and demographics.

“Risk assessment and treatments for children are often adapted from research on adults with PAH,” the study’s authors wrote. “However, there are inherent differences in the etiology, natural history, and treatment response for children.”

Among the 169 children included in this analysis (n = 47 with syncope; n = 122 without syncope), syncope was seen in 28% during their follow-up and idiopathic PAH was their most common disease subtype (76%); PAH associated with congenital heart disease was the most common subtype in the nonsyncope group (67%).

The children in the syncope group had an older median (IQR) age at diagnosis compared with those who did not have syncope, 7.9 (0.4-19) vs 3.0 years (0-18.4) (P = .002), and they had 64% higher pulmonary vascular resistance at baseline: 14.9 vs 9.1 WU/m² (P = .01). All patients included in the analysis were 18 years or younger.

Rates of chest pain (P = .022) and fatigue (P = .003) were also higher among the children with syncope, and acute vasodilator testing with inhaled nitric oxide led to a vasoresponse among more of them compared with those who did not have syncope: 33% vs 22% (P = .08-NS).

Those who did not have cardiac shunts (n = 109) at diagnosis underwent cardiac catheterization, and a subanalysis of the outcomes for those on vs not on medication and those who did not have syncope, respectively, showed the highest baseline indexed pulmonary vascular resistance among those with syncope on medication: 20.1 (9.2-25.1) vs 13.7 (8.8-22.0) vs 9.05 (5.3-14.5) WU/m² (P = .04).

In addition, acute vasodilator testing with inhaled nitric oxide showed the highest mean (SD) pulmonary arterial pressure, ratio of pulmonary artery/systemic arterial systolic pressure, and indexed pulmonary vascular resistance were seen among those with syncope on medication vs no medication and no syncope, respectively:

• Mean pulmonary arterial pressure: 63 (53-66.5) vs 38 (27-60) vs 37.5 (28-56.5) mm Hg
• Ratio: 0.77 (0.67-1.16) vs 0.60 (0.40-0.92) vs0.65 (0.46-0.89)
• Indexed pulmonary vascular resistance: 15.1 (11.9-19.5) vs 9.3 (5.1-17.3) vs 6.5 (3.7-11.0) WU/m²

Among those still in the study at its final follow-up (n = 42 from the syncope group and 67 from the nonsyncope group), the most common treatment regimens in the syncope group were intravenous/subcutaneous prostanoids (48%), triplet PAH therapy (43%), and doublet PAH therapy (31%). In the nonsyncope group, these were triplet PAH therapy (34%), single PAH therapy (27%), and intravenous/subcutaneous prostanoids (22%).

Overall, patients with syncope had a higher median risk score compared with patients who did not have syncope, 1.8 (1.57-2.00) vs 1.47 (1.28-1.67) and their long-term survival was worse.

“In adults with PAH, syncope is an independent predictor of poos outcomes, as it is nearly always reflective of right heart failure leading to insufficient cardiac output,” the authors wrote nof their findings. “This appears to hold true in children with syncope without vasoresponsiveness or despite appropriate targeted therapy.”

Two suggestions to make inroads in the pediatric population with PAH are to have a risk score system specifically geared for these patients and for larger prospective studies to take place the further investigate “syncope as a marker for a vasoreactive phenotype, with implications for treatment and long-term outcomes.”

Reference

Linder AN, Hsia J, Krishnan SV, Rosenzweig EB, Krishnan US. Vasoreactive phenotype in children with pulmonary arterial hypertension and syncope. ERJ Open Res. Published online October 10, 2022. doi:10.1183/23120541.00223-2022