Pulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension

doi:10.1016/j.jpeds.2016.10.003

The Journal of Pediatrics

Volume 180, January 2017, Pages 75-79.e2

https://doi.org/10.1016/j.jpeds.2016.10.003 Get rights and content

Objectives

To evaluate the clinical utility of pulmonary artery capacitance index (PACi) in the assessment of disease severity and prognostic value in children with idiopathic and heritable pulmonary arterial hypertension (PAH).

Study Design

PACi is defined as the ratio of stroke volume index over pulmonary pulse pressure. A retrospective study was performed to compare PACi, brain natriuretic peptide (BNP), 6-minute walk distance, New York Heart association (NYHA) functional class, and adverse outcomes (hospitalization due to heart failure, lung transplantation, and cardiac mortality) in 72 Japanese children (10 ± 3.6 years) with idiopathic and heritable PAH.

Results

PACi had significant correlations with pulmonary vascular resistance index (r =−0.73, P < .0001), BNP levels (r = −0.40, P = .0008), and 6-minute walk distance (r = 0.57, P < .05). Statistically significant differences in PACi were observed between NYHA functional class II vs combined III and IV (median; 1.1 vs 0.6 mL/mm Hg/m², respectively, P < .05). There were 25 of 72 (35%) children who had an adverse event including initiation of hospitalization due to heart failure, lung transplantation, and death. Cumulative event-free survival rate was significantly lower when PACi was <0.85 mL/mm Hg/m² (log-rank test, P < .0001).

Conclusions

PACi correlated with BNP and NYHA functional class and may serve as a strong prognostic marker in children with idiopathic and heritable PAH.

Section snippets

Methods

We retrospectively reviewed hemodynamic data evaluated by cardiac catheterization and clinical data of 72 children diagnosed with idiopathic and heritable PAH. All children (18 years or younger of age at diagnosis) were followed at Toho University Omori Medical Center (Tokyo, Japan) between 1998 and 2015. Patients with associated PAH due to congenital heart disease, secondary to left-sided obstructive lesions (pulmonary venous hypertension), or persistent pulmonary hypertension of the newborn

Results

Table I presents the clinical characteristics of the pediatric patients. Overall, 55 patients with idiopathic PAH and 17 with heritable PAH were enrolled. The age at diagnosis was 9.8 ± 3.7 years, with 38 male and 34 female patients. In all, 50 children (69%) were administrated epoprostenol infusion therapy during follow-up, and the remaining 22 children received oral vasodilators.

Discussion

We found that PACi had a significant correlation with disease severity including hemodynamic variables, BNP levels, 6MWD, and NYHA functional class and predicted adverse outcomes. The capacitance is the distensibility of the pulmonary arterial tree and is an important component of RV workload. Although normal pulmonary vessels have the capacity to dilate, in PAH pulmonary arterial capacitance is diminished or lost, leading to increased pulmonary artery pressure and RV hypertrophy. As RV

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Clinical and Hemodynamic Correlates of Pulmonary Arterial Stiffness in Incident, Untreated Patients With Idiopathic Pulmonary Arterial Hypertension
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Citation Excerpt :
These findings warrant further confirmation in other PH populations. Several previous studies have reported the prognostic importance of C (1/stiffness) in precapillary PH from various etiologies,7-10,33,34 but the relatively limited number of patients included and the lack of independent testing of the contribution of stroke volume per se has been strengthened.19 Our study was a subgroup of a previously published cohort, and the survival results must be viewed as essentially redundant rather than confirmatory.
The role of decreased pulmonary arterial (PA) compliance (C), equivalent to increased PA stiffness (1/C), as a critical determinant of right ventricular dysfunction and prognosis has been emphasized in pulmonary arterial hypertension (PAH).
This study retrospectively reviewed all incident patients diagnosed with idiopathic PAH according to right heart catheterization who were enrolled in the French Pulmonary Arterial Hypertension Network registry between 2006 and 2016 and who had complete baseline data allowing calculation of stiffness (PA pulse pressure/stroke volume index).
In the 719 patients included (median age: 66 years; 53.7% female), PA stiffness was 1.49 mm Hg × m²/mL (interquartile ratio: 1.08-2.04 mm Hg × m²/mL). Stiffness was related to mean pulmonary artery pressure (mPAP) (r² = 0.33) and heart rate (r² = 0.15) but not to age or sex. Higher PA stiffness and higher pulmonary vascular resistance (PVR) were documented in high-risk vs low-risk patients, as defined according to the European Society of Cardiology/European Respiratory Society guidelines. The dispersion of the PVR × C product was as variable as patient age and mPAP, and C could not be estimated on the basis of PVR alone (95% limits of agreement of the bias: –50% to 54%). Although transplant-free survival differed across PA stiffness quartiles (P = .04), stiffness was not an independent predictor of long-term outcome (median follow-up duration: 2.43 years).
In incident idiopathic PAH, PA stiffness was related to mPAP and heart rate, and this finding outperformed the potential influences of age and sex. Baseline PA stiffness did not independently predict outcome. The great dispersion of the PVR × C product implied that PVR and PA stiffness were differently affected by the disease process.
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: Supported by the Jayden DeLuca Foundation, the Leah Bult Foundation, Colorado Clinical Translational Science Institute (UL1 TR001082), National Center for Research Resources, and National Institutes of Health. The University of Colorado contracts with Actelion, Bayer, Lilly, and United Therapeutics. D.I. serves as a member of the Gilead Sciences Research Scholars Program. The other authors declare no conflicts of interest.

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Original ArticlesPulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension

Objectives

Study Design

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am Heart J

Chest

J Am Coll Cardiol

JACC Heart Fail

Am Heart J

Int J Cardiol

J Am Coll Cardiol

J Am Soc Echocardiogr

Am Heart J

Original Articles
Pulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension