Hemodynamic Evaluation of Children with Persistent or Recurrent Pulmonary Arterial Hypertension Following Complete Repair of Congenital Heart Disease
- 293 Downloads
Persistent or recurrent pulmonary arterial hypertension (PAH) following complete surgical repair of congenital heart disease (CHD) represents one of the largest group of PAH associated with CHD (PAH-CHD) in recent registry studies and seems to have a particularly poor prognosis. However, little is known about this fourth clinical subclass of PAH-CHD, especially in children. The purpose of this study was to assess specific characteristics of invasive hemodynamics of this disease in children, including acute vasodilator testing (AVT) and pulmonary endothelial function (PEF) and to compare to patients with idiopathic PAH (IPAH), who usually present with a similar fatal clinical course. Thirty-two children with PAH were included in the study, twelve of these patients had PAH-CHD subclass 4 (mean age 8.0 ± 3.4 years) and twenty children had IPAH (mean age 8.6 ± 4.4 years). Cardiac catheterization was performed in all children, including AVT and PEF. PEF was assessed by changes in pulmonary blood flow in response to acetylcholine (Ach) using Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. At baseline, the ratio of mean PA pressure to mean systemic arterial pressure (mPAP/mSAP) was comparably high in both groups (0.78 ± 0.32 vs. 0.80 ± 0.22), while the indexed pulmonary vascular resistance (PVRI) was significantly lower in the PAH-CHD group (12.6 ± 6.8 WUxm2) compared to IPAH patients (19.9 ± 10.6 WUxm2) (p = 0.04). Cardiac index was significantly higher in the PAH-CHD group (4.19 ± 1.09 l/min/m2 vs. 3.23 ± 0.76) (p = 0.017). However, AVT revealed a significantly larger maximum response (percentage of fall of PVR/SVR ratio during AVT) in the IPAH group (37 ± 22%) compared to the PAH-CHD group (13 ± 23%) (p = 0.017). PEF showed no significant difference between both patient groups (PFR 1.69 ± 0.71 vs. 1.73 ± 0.68) (p = 0.76). Our study demonstrates significant pulmonary vascular disease in children with persistent or recurrent PAH following complete surgical repair of CHD similar to IPAH patients. Although baseline measures appeared to be more favorable, pulmonary vasoreactivity was markedly impaired in PAH-CHD subclass 4, which may contribute to its negative impact on the long-term outcome of this patient group.
KeywordsIdiopathic pulmonary arterial hypertension Pulmonary arterial hypertension associated with congenital heart disease Endothelial dysfunction Pulmonary flow reserve
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 2.Manes A, Palazzini M, Leci E, Bacchi Reggiani ML, Branzi A, Galie N (2014) Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups. Eur Heart J 35(11):716–724. doi: 10.1093/eurheartj/eht072 CrossRefPubMedGoogle Scholar
- 4.Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L, Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G (2013) Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 369(9):809–818. doi: 10.1056/NEJMoa1213917 CrossRefPubMedGoogle Scholar
- 5.Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galie N, Ghofrani HA, Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV, Investigators G (2015) Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med 373(26):2522–2533. doi: 10.1056/NEJMoa1503184 CrossRefPubMedGoogle Scholar
- 8.Apitz C, Hansmann G, Schranz D (2016) Hemodynamic assessment and acute pulmonary vasoreactivity testing in the evaluation of children with pulmonary vascular disease. Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 102(Suppl 2):ii23–ii29. doi: 10.1136/heartjnl-2014-307340 CrossRefPubMedGoogle Scholar
- 10.Apitz C, Zimmermann R, Kreuder J, Jux C, Latus H, Pons-Kuhnemann J, Kock I, Bride P, Kreymborg KG, Michel-Behnke I, Schranz D (2012) Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension. J Am Coll Cardiol 60(2):157–164. doi: 10.1016/j.jacc.2012.04.010 CrossRefPubMedGoogle Scholar
- 11.Latus H, Werz A, Kock I, Rupp S, Kerst G, Kreuder J, Schranz D, Apitz C (2014) Systemic arterial endothelial function in children and young adults with idiopathic pulmonary arterial hypertension: is there a relation to pulmonary endothelium-dependent relaxation? Pediatr Cardiol 35(5):844–850. doi: 10.1007/s00246-014-0864-z CrossRefPubMedGoogle Scholar
- 13.Douwes JM, Humpl T, Bonnet D, Beghetti M, Ivy DD, Berger RM, Investigators T (2016) Acute vasodilator response in pediatric pulmonary arterial hypertension: current clinical practice from the TOPP REGISTRY. J Am Coll Cardiol 67(11):1312–1323. doi: 10.1016/j.jacc.2016.01.015 CrossRefPubMedGoogle Scholar
- 14.van Loon RL, Roofthooft MT, Hillege HL, ten Harkel AD, van Osch-Gevers M, Delhaas T, Kapusta L, Strengers JL, Rammeloo L, Clur SA, Mulder BJ, Berger RM (2011) Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation 124(16):1755–1764. doi: 10.1161/CIRCULATIONAHA.110.969584 CrossRefPubMedGoogle Scholar
- 15.Douwes JM, van Loon RL, Hoendermis ES, Vonk-Noordegraaf A, Roofthooft MT, Talsma MD, Hillege HL, Berger RM (2011) Acute pulmonary vasodilator response in paediatric and adult pulmonary arterial hypertension: occurrence and prognostic value when comparing three response criteria. Eur Heart J 32(24):3137–3146. doi: 10.1093/eurheartj/ehr282 CrossRefPubMedGoogle Scholar