Survival of Left-to-Right Shunt Repair in Children with Pulmonary Arterial Hypertension at a Tertiary Hospital in a Low-to-Middle-Income Country

Nadya Arafuri; Indah K. Murni; Nikmah S. Idris; Cuno S. P. M. Uiterwaal; Ary I. Savitri; Sasmito Nugroho; Noormanto Noormanto

doi:10.5334/gh.831

Survival of Left-to-Right Shunt Repair in Children with Pulmonary Arterial Hypertension at a Tertiary Hospital in a Low-to-Middle-Income Country

Volume 16 (2021): Issue 1

By: Nadya Arafuri , Indah K. Murni, Nikmah S. Idris, Cuno S. P. M. Uiterwaal, Ary I. Savitri, Sasmito Nugroho and Noormanto Noormanto

Open Access

|Apr 2021

Abstract

Background: In low-to-middle-income countries, repair of the left-to-right shunts congenital heart disease (CHD) are often done with existing pulmonary arterial hypertension (PAH). Long-term outcomes data of this condition in either low-to-middle or high-income countries are limited. We conducted a study to evaluate the outcomes of children with PAH related to left-to-right shunt CHD who underwent surgical or transcatheter repair.

Methods: All cases of PAH related to left-to-right shunt CHD repairs from 2015–2018 were retrospectively reviewed with additional new patients who underwent repair within our study period (2019–2020). Cases with complex congenital heart disease and incomplete hemodynamic echocardiography or catheterization measurements were excluded. Kaplan-Meier curves, log-rank test, Cox regression with Firth’s correction and restricted mean survival time were used for survival analysis.

Results: Of the 118 patients, 103 patients were enrolled and 15 patients were excluded due to complex congenital heart disease and missing hemodynamic measurements prior to repair. Overall, median age at intervention was 44 months, mPAP mean was 43.17 ± 16.05 mmHg and Pulmonary Vascular Resistance index (PVRi) mean was 2.84 ± 2.09 (WU.m²). Nine patients died after repair. The survival rate for patients with PAH-CHD at 1 day, 30 days and 1400 days (4 years) was 96.1%, 92.1%, and 91.0% respectively. Patients with persisting PAH after correction had –476.1 days (95% confidence interval [CI]: –714.4, –237,8) shorter survival over 4 years of follow up compared to patients with reversed PAH. PVRi was found to be the influencing covariate of the difference of restricted mean survival time between these groups.

Conclusion: In low-to-middle income settings, with accurate PAH reversibility assessment prior to intervention, repair of left-to-right shunt CHD with existing PAH in children has a favourable outcome. Inferior survival is found in patients with persistence of PAH. PVRi at baseline predicts between-group survival difference.

References

Ivy DD, Abman SH, Barst RJ, et al. Pediatric pulmonary hypertension. J Am Coll Cardiol. 2013; 62(25 SUPPL.). DOI: 10.1016/j.jacc.2013.10.028
Open DOI Search in Google Scholar Back to article
Abman SH, Hansmann G, Archer SL, et al. Pediatric pulmonary hypertension. Circulation. 2015; (132): 2037–2099. DOI: 10.1161/CIR.0000000000000329
Open DOI Search in Google Scholar Back to article
Barst RJ, McGoon MD, Elliott CG, Foreman AJ, Miller DP, Ivy DD. Survival in childhood pulmonary arterial hypertension: Insights from the registry to evaluate early and long-term pulmonary arterial hypertension disease management. Circulation. 2012; 125(1): 113–22. DOI: 10.1161/CIRCULATIONAHA.111.026591
Open DOI Search in Google Scholar Back to article
Rosenzweig EB, Abman SH, Adatia I, et al. Paediatric pulmonary arterial hypertension: Updates on definition, classification, diagnostics and management. Eur Respir J [Internet]. 2019; 53(1). DOI: 10.1183/13993003.01916-2018
Open DOI Search in Google Scholar Back to article
Kozlik-Feldmann R, Hansmann G, Bonnet D, Schranz D, Apitz C, Michel-Behnke I. Pulmonary hypertension in children with congenital heart disease (PAH-CHD, PPHVD-CHD). 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. 2016; 102: ii42–8. DOI: 10.1136/heartjnl-2015-308378
Open DOI Search in Google Scholar Back to article
Van Der Feen DE, Bartelds B, De Boer RA, Berger RMF. Assessment of reversibility in pulmonary arterial hypertension and congenital heart disease. Heart. 2019; 105(4): 276–82. DOI: 10.1136/heartjnl-2018-314025
Open DOI Search in Google Scholar Back to article
Mocumbi AO, Lameira E, Yaksh A, Paul L, Ferreira MB, Sidi D. Challenges on the management of congenital heart disease in developing countries. Int J Cardiol [Internet]. 2011; 148(3): 285–8. DOI: 10.1016/j.ijcard.2009.11.006
Open DOI Search in Google Scholar Back to article
Alonso-Gonzalez R, Lopez-Guarch CJ, Subirana-Domenech MT, et al. Pulmonary hypertension and congenital heart disease: An insight from the REHAP national registry. Int J Cardiol [Internet]. 2015; 184(1): 717–23. DOI: 10.1016/j.ijcard.2015.02.031
Open DOI Search in Google Scholar Back to article
Saxena A, Ramakrishnan S, Tandon R, et al. Consensus on timing of intervention for common congenital heart diseases. Indian Pediatr. 2008; 45: 117–26.
Search in Google Scholar Back to article
Talwar S, Keshri VK, Choudhary SK, et al. Surgical strategies for patients with congenital heart disease and severe pulmonary hypertension in low/middle-income countries. Heart Asia. 2015; 7(2): 31–317.
Search in Google Scholar Back to article
Myers PO, Tissot C, Beghetti M. Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease – Do we have the good tools to predict success? Circ J. 2014; 78(1): 4–11. DOI: 10.1253/circj.CJ-13-1263
Open DOI Search in Google Scholar Back to article
Berger RMF, Beghetti M, Humpl T, et al. Clinical features of paediatric pulmonary hypertension: A registry study. Lancet [Internet]. 2012; 379(9815): 537–46. DOI: 10.1016/S0140-6736(11)61621-8
Open DOI Search in Google Scholar Back to article
Zuckerman WA, Krishnan U, Rosenzweig EB. Pulmonary arterial hypertension associated with congenital heart disease. Curr Pediatr Rep. 2013; 1(2): 92–101. DOI: 10.1007/s40124-013-0015-7
Open DOI Search in Google Scholar Back to article
Murni IK, Djer MM, Yanuarso PB, et al. Outcome of pediatric cardiac surgery and predictors of major complication in a developing country. Ann Pediatr Cardiol. 2019; 12(1): 38–44. DOI: 10.4103/apc.APC_146_17
Open DOI Search in Google Scholar Back to article
Vijarnsorn C, Durongpisitkul K, Chungsomprasong P, et al. Contemporary survival of patients with pulmonary arterial hypertension and congenital systemic to pulmonary shunts. PLoS One. 2018; 13(4): 1–18. DOI: 10.1371/journal.pone.0195092
Open DOI Search in Google Scholar Back to article
Kumar RK, Viswanathan S. Hemodynamic assessment of congenital heart defects with left to right shunts and pulmonary hypertension. J Indian Coll Cardiol [Internet]. 2011; 1(1): 28–35. DOI: 10.1016/S1561-8811(11)80015-5
Open DOI Search in Google Scholar Back to article
Bhalgat PS, Pinto R, Dalvi BV. Transcatheter closure of large patent ductus arteriosus with severe pulmonary arterial hypertension: Short- and intermediate-term results. Ann Pediatr Cardiol. 2012; 5(2): 135–40. DOI: 10.4103/0974-2069.99614
Open DOI Search in Google Scholar Back to article
Feng J, Kong X, Sheng Y, Yang R. Patent ductus arteriosus with persistent pulmonary artery hypertension after transcatheter closure. Ther Clin Risk Manag. 2016; 12: 1609–13. DOI: 10.2147/TCRM.S112400
Open DOI Search in Google Scholar Back to article
Charisopoulou D, Bini RM, Riley G, Janagarajan K, Moledina S, Marek J. Repair of isolated atrial septal defect in infants less than 12 months improves symptoms of chronic lung disease or shunt-related pulmonary hypertension. Cardiol Young. 2020. DOI: 10.1017/S1047951120000463
Open DOI Search in Google Scholar Back to article
Van Loon RLE, Roofthooft MTR, Hillege HL, et al. Pediatric pulmonary hypertension in the Netherlands: Epidemiology and characterization during the period 1991 to 2005. Circulation. 2011; 124(16): 1755–64. DOI: 10.1161/CIRCULATIONAHA.110.969584
Open DOI Search in Google Scholar Back to article
Murni IK, Musa NL. The need for specialized pediatric cardiac critical care training program in limited resource settings. Front Pediatr. 2018; 6(March): 1–5. DOI: 10.3389/fped.2018.00059
Open DOI Search in Google Scholar Back to article
Manes A, Palazzini M, Leci E, Bacchi Reggiani ML, Branzi A, Galiè N. Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: A comparison between clinical subgroups. Eur Heart J. 2014; 35(11): 716–24. DOI: 10.1093/eurheartj/eht072
Open DOI Search in Google Scholar Back to article
Xi SB, Wang SS, Qian MY, et al. Predictors of operability in children with severe pulmonary hypertension associated with congenital heart disease. Chin Med J (Engl). 2019; 132(7): 811–8. DOI: 10.1097/CM9.0000000000000145
Open DOI Search in Google Scholar Back to article
Barst RJ, Ivy DD, Foreman AJ, McGoon MD, Rosenzweig EB. Four- and seven-year outcomes of patients with congenital heart disease-associated pulmonary arterial hypertension (from the REVEAL Registry). Am J Cardiol [Internet]. 2014; 113(1): 147–55. DOI: 10.1016/j.amjcard.2013.09.032
Open DOI Search in Google Scholar Back to article
Thomaz AM, Kajita LJ, Aiello VD, et al. Parameters associated with outcome in pediatric patients with congenital heart disease and pulmonary hypertension subjected to combined vasodilator and surgical treatments. Pulm Circ. 2019; 9(3): 1–13. DOI: 10.1177/2045894019837885
Open DOI Search in Google Scholar Back to article
Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013; 62(25 SUPPL.). DOI: 10.1016/j.jacc.2013.10.029
Open DOI Search in Google Scholar Back to article
Ranard LS, Mallah WEl, Awerbach JD, et al. Impact of Pulmonary Hypertension on Survival Following Device Closure of Atrial Septal Defects. Am J Cardiol [Internet]. 2019; 124(9): 1460–4. DOI: 10.1016/j.amjcard.2019.07.042
Open DOI Search in Google Scholar Back to article
Barst RJ, Chung L, Zamanian RT, Turner M, McGoon MD. Functional class improvement and 3-year survival outcomes in patients with pulmonary arterial hypertension in the REVEAL registry. Chest [Internet]. 2013; 144(1): 160–8. DOI: 10.1378/chest.12-2417
Open DOI Search in Google Scholar Back to article
Wang LY, Lee KT, Lin CP, et al. Long-term survival of patients with pulmonary arterial hypertension at a single center in Taiwan. Acta Cardiol Sin. 2017; 33(5): 498–509.
Search in Google Scholar Back to article
Lammers AE, Adatia I, Del Cerro MJ, et al. Functional classification of pulmonary hypertension in children: Report from the PVRI pediatric taskforce, Panama 2011. Pulm Circ. 2011; 1(2): 280–5. DOI: 10.4103/2045-8932.83445
Open DOI Search in Google Scholar Back to article
Ryan JJ, Huston J, Kutty S, et al. Right Ventricular Adaptation and Failure in Pulmonary Arterial Hypertension. Can J Cardiol. 2015; 31(4): 391–406. DOI: 10.1016/j.cjca.2015.01.023
Open DOI Search in Google Scholar Back to article
Lindberg L, Olsson AK, Jögi P, Jonmarker C. How common is severe pulmonary hypertension after pediatric cardiac surgery? J Thorac Cardiovasc Surg. 2002; 123(6): 1155–63. DOI: 10.1067/mtc.2002.121497
Open DOI Search in Google Scholar Back to article
Brunner N, de Jesus Perez VA, Richter A, et al. Perioperative pharmacological management of pulmonary hypertensive crisis during congenital heart surgery. Pulm Circ. 2014; 4(1): 10–24. DOI: 10.1086/674885
Open DOI Search in Google Scholar Back to article
Macrae DJ, Field D, Mercier JC, et al. Inhaled nitric oxide therapy in neonates and children: Reaching a European consensus. Intensive Care Med. 2004; 30(3): 372–80. DOI: 10.1007/s00134-003-2122-3
Open DOI Search in Google Scholar Back to article
Bizzarro M, Gross I, Barbosa FT. Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease. Cochrane Database Syst Rev. 2014; 2014(7). DOI: 10.1002/14651858.CD005055.pub3
Open DOI Search in Google Scholar Back to article
Majure DT, Greco T, Greco M, et al. Meta-analysis of randomized trials of effect of milrinone on mortality in cardiac surgery: An update. J Cardiothorac Vasc Anesth [Internet]. 2013; 27(2): 220–9. DOI: 10.1053/j.jvca.2012.08.005
Open DOI Search in Google Scholar Back to article
Trachte AL, Lobato EB, Urdaneta F, et al. Oral sildenafil reduces pulmonary hypertension after cardiac surgery. Ann Thorac Surg. 2005; 79(1): 194–7. DOI: 10.1016/j.athoracsur.2004.06.086
Open DOI Search in Google Scholar Back to article
Kwan WC, Shavelle DM, Laughrun DR. Pulmonary vascular resistance index: Getting the units right and why it matters. Clin Cardiol. 2019; 42(3): 334–8. DOI: 10.1002/clc.23151
Open DOI Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.5334/gh.831 | Journal eISSN: 2211-8179

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Language: English

Submitted on: May 27, 2020

Accepted on: Mar 24, 2021

Published on: Apr 21, 2021

Published by: Ubiquity Press

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

Keywords:

Congenital heart disease,

pulmonary arterial hypertension,

cardiac surgery,

transcatheter closure,

survival,

children

© 2021 Nadya Arafuri, Indah K. Murni, Nikmah S. Idris, Cuno S. P. M. Uiterwaal, Ary I. Savitri, Sasmito Nugroho, Noormanto Noormanto, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 16 (2021): Issue 1