Pulmonary Hypertension in Congenital Heart Disease

1. Pulmonary Hypertension in Congenital Heart Disease Greg Latham, MD Associate Professor Seattle Children’s Hospital gregory.latham@seattlechildrens.org Updated 4/2017

2. Disclosures No disclosures to report

3. Objectives • Review fetal circulation, simple intracardiac shunts, and causes of pulmonary over-circulation • Define and categorize pulmonary hypertension • Describe congenital heart disease-induced pulmonary hypertension

4. Fetal and Transitional Circulation

5. Children’s Hospital of Wisconsin. http://www.chw.org/display/PPF/DocID/23045/router.asp

6. Fetal Circulation • Course of the oxygenated umbilical vein blood: •  bypasses liver via ductus venosus •  mixes with IVC •  eustachian valve shunts towards PFO  LA •  LA  LV •  aortic valve  head and neck arteries • Therefore, oxygenated blood from the umbilical vein perfuses the brain and coronary arteries by shunting across the liver (via the ductus venosus) and shunting across the right heart (via the foramen ovale) • See diagram on next slide

7. SVC Aorta PA PFO RA EuV LV RV Ductus venosus Liver Umbilical vein IVC Greg Latham, MD

8. Fetal Circulation • Desaturated SVC blood from the fetal brain takes a different course: • SVC RA  tricuspid valve (not to PFO) •  pulmonary valve •  ductus arteriosus •  descending aorta •  back to placenta for oxygenation • See diagram on next slide

9. PDA SVC Aorta PA RA TV LV RV Ductus venosus Liver Umbilical vein IVC Greg Latham, MD

10. Fetal Circulation Yellow arrow – eustachian valve Red arrow – flow of umbilical blood Blue arrow – flow of desaturated blood http://bookdome.com/health/anatomy/Human-Body-Structure/85-The-Heart-In-Mammals.html

11. Transitional Circulation - PFO • Transitional circulation begins when umbilical cord is clamped and lungs are inflated • Cord clamping removes the low resistance placenta from the circulation and raises SVR • Lung inflation and increased PaO2 lowers PVR dramatically, causing increased pulmonary blood flow and increased blood return to the left atrium • pLA > pRA  closes the flap of tissue covering the PFO • Functional closure occurs quickly but anatomic closure usually requires weeks. A PFO that is probe patent persists in approximately 25% of adults

12. Transitional Circulation - PDA • The ductus arteriosus remains patent in utero due to hypoxia, mild acidosis and placental prostaglandins. Removal of these factors after delivery causes functional closure with anatomic closure occurring weeks later • Persistent PDA often occurs in premature infants with lung disease. Indomethacin, via its anti-prostaglandin action can be used to try and close a PDA • Before anatomic closure of the PDA and PFO, pRA > pLA can cause reversion to fetal circulation (R  L shunt and cyanosis) • Hypothermia, hypercarbia, acidosis, hypoxia and sepsis can all cause a reversion to fetal circulation

13. Pulmonary Arterial Hypertension (PAH)

14. PAH Definition

15. PAH Classification • The classification of adult & peds PAH is big • In young children, persistent pulmonary hypertension of the newborn (PPHN) and CHD are the primary causes (>80%) • Idiopathic PAH, although less common, is an important cause in children Simonneau, G., et al. (2013). Updated Clinical Classification of Pulmonary Hypertension. Journal of the American College of Cardiology, 62(25), D34–D41.

16. Why Does PAH Occur in Children? •  pLA • LV systolic/diastolic dysfunction • MV or AV stenosis/regurgitation • Pulmonary vein obstruction •  pulmonary blood flow • Congenital heart disease with L  R shunt •  PVR • Pulmonary parenchymal disease • Thromboembolic disease

17. PAH Associated with Congenital Heart Disease (CHD)

18. CHD-associated PAH • PAH is major acquired complication of CHD with L  R shunts • PAH causes increased morbidity and mortality • PAH may prevent complete repair in those with advanced pulmonary vascular disease • 15%-30% of the CHD population is thought to develop at least transient PAH Kidd L, Driscoll DJ, Gersony WM, et al. Second natural history study of congenital heart defects: results of treatment of patients with ventricular septal defects. Circulation 1993;87 (2, Suppl):I38–I51

19. Cause of CHD-associated PAH • L  R shunt • Increases pulmonary blood flow, leading to pulmonary vascular injury and shear stress, then • Leads to progressive smooth muscle hypertrophy and hyperplasia, intimal proliferation, and pulmonary vasoconstriction Open Access License: Tian X, Vroom C, Ghofrani HA, et al. Phosphodiesterase 10A Upregulation Contributes to Pulmonary Vascular Remodeling. El-Rifai W, ed. PLoS ONE. 2011;6(4):e18136. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073929/)

20. Cause of CHD-associated PAH • Risk factors for PAH in children with CHD: • Type of defect: • High risk: truncus arteriosus, AV canal, TGA with VSD • Almost 100% risk if untreated • Moderate risk: VSD (risk of Eisenmenger’s syndrome if untreated: 3% when <1.5cm; 50% when >1.5cm), PDA • Low risk: ASD, PAPVR • Pressure and flow of LR shunt • Presence of associated noncardiac syndromes (especially Down syndrome)

21. When Does CHD-PAH Develop? • The age at which congenital heart lesions cause irreversible pulmonary vascular disease varies • Endothelial changes occur as early as 2 months after birth in some children with increased pulmonary blood flow • The type of CHD matters; combination of high pressure and high flow causes more rapid and severe remodeling • Clinical onset ranges from as early as 4-6 months in CAVC or truncus arteriosus to never in small ASDs or VSDs • The pulmonary vascular remodeling process is reversible in the early stages of the disease

22. Eisenmenger Syndrome (ES) • The most severe form of CHD-associated PAH • Definition: • “CHD with an initial large systemic-to-pulmonary shunt that induces progressive pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis” • When shunt reversal occurs, symptoms include: • Cyanosis, dyspnea, fatigue, dizziness, syncope, and arrhythmia • Poor exercise tolerance • Life expectancy is markedly reduced Lee J, Kwon HM, Hong BK, et al. Total Occlusion of Left Main Coronary Artery by Dilated Main Pulmonary Artery in a Patient with Severe Pulmonary Hypertension. The Korean Journal of Internal Medicine. 2001;16(4):265-269. 

23. Conclusion • CHD is a frequent and important cause of PAH in children. • Early repair of congenital cardiac lesions with intensive postoperative care is the best strategy to prevent the development of progressive PAH in CHD. • Once PAH develops, aggressive medical treatment ensues in the hopes of reversibility. • Chronic PAH increase morbidity and mortality, and anesthetic management must be carefully considered!

24. References • Kidd L, Driscoll DJ, Gersony WM, et al. Second natural history study of congenital heart defects: results of treatment of patients with ventricular septal defects. Circulation 1993;87 (2, Suppl):I38–I51 • Simonneau, G., et al. (2013). Updated Clinical Classification of Pulmonary Hypertension. Journal of the American College of Cardiology, 62(25), D34–D41. • van Loon, R. L. E., Roofthooft, M. T. R., Hillege, H. L., Harkel, ten, A. D. J., van Osch-Gevers, M., Delhaas, T., et al. (2011). Pediatric pulmonary hypertension in the Netherlands: epidemiology and characterization during the period 1991 to 2005. Circulation, 124(16), 1755–1764. Suggested Reading: • Friesen, R. H., & Williams, G. D. (2008). Anesthetic management of children with pulmonary arterial hypertension. Pediatric Anesthesia, 18(3), 208–216 • Shukla, A. C., & Almodovar, M. C. (2010). Anesthesia considerations for children with pulmonary hypertension. Pediatric Critical Care Medicine, 11(2), S70–S73 • Beghetti, M., & Tissot, C. (2009). Pulmonary Arterial Hypertension in Congenital Heart Diseases. Seminars in Respiratory and Critical Care Medicine, 30(04), 421–428 • Taylor, K., Moulton, D., Zhao, X. Y., & Laussen, P. (2015). The impact of targeted therapies for pulmonary hypertension on pediatric intraoperative morbidity or mortality. Anesthesia & Analgesia, 120(2), 420–426. • Chau, D. F., Gangadharan, M., Hartke, L. P., & Twite, M. D. (2016). The Post-Anesthetic Care of Pediatric Patients With Pulmonary Hypertension. Seminars in Cardiothoracic and Vascular Anesthesia, 20(1), 63–73.