Fainting in Children With PAH May Not Signal Poor Outcomes: Study
For pediatric PAH patients, response to vasodilator test appears more important
Children with episodes of fainting due to pulmonary arterial hypertension (PAH) who respond well to a vasodilator given in a challenge test are likely to have better long-term outcomes than those who respond poorly, a long-term records study suggests.
A vasodilator challenge is a test to measure blood pressure in response to vasodilators, medications that widen or dilate blood vessels to ease disease symptoms.
These findings suggest that in some PAH children, fainting episodes — a condition called syncope — may reflect an acute narrowing of blood vessels in response to an adverse stimulus. They are not associated with poor outcomes in these young patients, unlike syncope episodes in adults with PAH, the researchers wrote.
A larger study in children with PAH that includes imaging of heart function may help in better understanding the implications of syncope at young ages, they added.
Fainting with pediatric PAH not as well studied as syncope in PAH adults
The analysis, “Vasoreactive phenotype in children with pulmonary arterial hypertension and syncope,” was published in the journal ERJ Open Research.
In PAH, the narrowing of the pulmonary arteries, which transport blood through the lungs, increases blood pressure and makes the right ventricle of the heart work harder to pump blood.
Fainting or syncope is a common PAH symptom, thought to be caused by right ventricle impairment and an inability to increase the amount of blood pumped by the heart, particularly during greater physical activity. In PAH adults, syncope is associated with poor survival due to advanced pulmonary artery disease and right ventricular failure.
Little is known about the mechanisms of syncope and how it affects disease outcomes in children with PAH, the researchers noted.
Normally, blood vessels widen (vasodilation) or narrow (vasoconstriction) in response to specific stimulation, typically due to blood flow needs.
Researchers at Columbia University Irving Medical Center and Children’s Hospital of Philadelphia wondered whether syncope in children with PAH might be due to a sudden narrowing of blood vessels in response to adverse stimuli among those more acutely responsive to blood vessel stimulation.
Vasodilator challenge, called acute vasodilator testing (AVT), was given to measure responsiveness to stimuli that trigger either vasodilation or vasoconstriction.
AVT is commonly used to identify PAH patients who may respond to calcium channel blockers — medications that widen blood vessels by preventing calcium from entering the cells of the heart and arteries. A positive AVT predicts response to these blockers.
AVT involved inhaling the vasodilator gas nitric oxide while undergoing right heart catheterization, the insertion of a catheter to measure blood pressure. Response to a vasodilator is defined as a drop in blood pressure without a drop in blood flow.
Researchers reviewed the medical records of 169 PAH patients, ages 18 and younger, treated at the New York center between 2005 and 2018. Patients were follow for up to 40 years or until their death, the study noted.
Forty-seven of these children (28%) had syncope and for 38 (81%) of them, syncope was the initial symptom before starting on PAH medications. Syncope patients were older at diagnosis than those without syncope (median of 7.9 vs. 3 years).
Survival better in those who respond to vasodilator challenge
PAH without a known cause, or idiopathic PAH, occurred more often in the syncope group. Three of five patients with heritable PAH had syncope, and all five were unresponsive to AVT.
Pulmonary vascular resistance (PVR), or resistance to blood flow, was higher in patients with syncope at diagnosis, with the highest resistance observed in those with initial syncope while on medications. PVR remained higher in those with syncope on medications during AVT, and none of these children were responsive, their records showed.
Notably, significantly more PAH children diagnosed with syncope were AVT-responsive than those without syncope. Overall, 40% of patients with syncope at diagnosis were responsive to AVT compared with 22% without syncope.
Regarding outcomes, nine of the children with syncope (28%) died during the study period, seven of causes related to PAH, and four underwent a lung transplant. Fourteen children (11%) without syncope died or underwent a lung transplant. Although there was no difference in event-free survival at 10 years, the likelihood of event-free survival was significantly higher in patients without syncope for the entire follow-up period.
The likelihood of survival was 100% for PAH children with syncope and an AVT response, the researchers noted. It was also 100% in children without syncope at diagnosis but an AVT response.
“Vasoresponders with syncope had similar baseline haemodynamics to non-vasoresponders, and survival was excellent in vasoresponders regardless of syncope,” the scientists wrote.
Likewise, while no significant differences in survival were seen between groups at 10 years, a significantly longer survival was evident in those with a response across follow-up. At diagnosis, those with syncope who responded to AVT had significantly better survival over this time.
In contrast, children with syncope who were AVT-unresponsive had significantly poorer long-term survival, “though this became significant only beyond 10 years of follow-up,” the researchers noted. Poorest outcomes were seen in non-responsive patients with syncope on PAH medications than in AVT responders with and without syncope.
Subtype analysis also showed that long-term survival was significantly poorer in non-AVT responsive idiopathic PAH patients with syncope. Those with syncope onset while on medication again had the poorest outcomes.
Syncope at diagnosis but a negative AVT response was associated with 50% survival at 15 years.
Finally, seven of the 34 PAH children with congenital heart disease had syncope. Eight patients with congenital heart disease were AVT responders, one of whom had syncope.
“Patients with syncope had higher rates of AVT response at diagnosis compared to those without syncope and had excellent outcomes with 100% survival over the entire follow-up period,” the researchers wrote.
“This suggests that in some children syncope may reflect acute pulmonary vasoconstriction to an adverse stimulus and is not associated with poor outcomes,” they added. Indeed, “AVT responsiveness may be associated with excellent outcomes even in the presence of syncope.”
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