Serum IL-6 levels are independently associated with RV function and RV-PA coupling in PAH. Patients with higher IL-6 levels have more severe RV dysfunction and diminished RV-PA coupling despite a comparable severity of pulmonary vascular disease.
Background
Patients with pulmonary hypertension caused by chronic lung disease (Group 3
PH
) have disproportionate right ventricle (
RV
) dysfunction, but the correlates and clinical implications of
RV
dysfunction in Group 3
PH
are not well defined.
Methods and Results
We performed a cohort study of 147 Group 3
PH
patients evaluated at the University of Minnesota.
RV
systolic function was quantified using right ventricular fractional area change (
RVFAC
) and
+
dP
/dt
max
/instantaneous pressure. Tau and
RV
diastolic stiffness characterized
RV
diastolic function. Multivariate linear regression was used to define correlates of
RVFAC
. Kaplan‐Meier and Cox proportional hazards analyses were used to examine freedom from heart failure hospitalization and death. Positive correlates of
RVFAC
on univariate analysis were pulmonary arterial compliance, cardiac index, and left ventricular diastolic dimension. Conversely, male sex, N‐terminal pro‐brain natriuretic peptide, heart rate, right atrial enlargement, mean pulmonary arterial pressure, and pulmonary vascular resistance were negative correlates. Male sex was the strongest predictor of lower
RVFAC
, after adjusting for pulmonary vascular resistance and pulmonary arterial compliance. When comparing sexes, males had lower
RVFAC
(26% versus 31%,
P
=0.03) both overall and for any given mean pulmonary arterial pressure and pulmonary vascular resistance value. Males exhibited a reduction in
+
dP
/dt
max
/instantaneous pressure as pulmonary vascular resistance increased, whereas females did not. There were no sex differences in
RV
diastolic function.
RV
dysfunction (
RVFAC
<28%) was associated with increased risk of heart failure hospitalization or death (hazard ratio: 1.84, 95%
CI
: 1.04–3.10,
P
=0.035).
Conclusions
Male sex is associated with
RV
dysfunction in Group 3
PH
, even after adjusting for
RV
afterload.
RV
dysfunction (
RVFAC
<28%) identifies Group 3
PH
patients at risk for poor outcomes.
Parental prostacyclin is the only therapy with a proven survival benefit in pulmonary arterial hypertension (PAH). However, some patients are unable to tolerate continuous prostacyclin infusion because of central line infection, side effects, or sociocultural factors. Selexipag is a recently approved prostacyclin receptor agonist that is able to blunt PAH disease progression. Although in the same molecular pathway, the interchangeability of selexipag with prostacyclin infusions is relatively unexplored. Here, we present a case series of five stable PAH patients who were functional class (FC) I or II that were transitioned from prostacyclin infusion to selexipag using a standardized protocol in the inpatient setting. We show that the transition to selexipag in five highly selected patients was tolerated with no significant changes in FC, minimal changes in pulmonary vascular disease severity, and no significant PAH-related complications. However, there was a trend for a reduction in cardiac index after transition to selexipag. These data suggest that a transition from prostacyclin infusion to selexipag can be achieved in clinically stable PAH patients who are unable to tolerate continuous prostacyclin infusion. However, this approach should only be selectively implemented at specialized centers with close follow-up due to the trend for a reduction in cardiac index after transition to selexipag.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.