Unraveling The Mysteries of The Lymphatic (“Forgotten”) Circulation in Patients With Single Ventricle Congenital Heart Disease: More Opportunities For Sedation/Anesthesia
Susan Nicolson MD, James DiNardo MD, Lindsey Loveland BaptistMD , Viviane Nasr MD
Original article
Kristensen R, Kelly B, Kim E, Dori Y, Hjortdal VE. Lymphatic Abnormalities on Magnetic Resonance Imaging In Single-Ventricle Congenital Heart Defects Before Glenn Operation. J Amer Heart Association 2023; 12: e029376 PMID: 37318013
Staged reconstructive surgery has improved survival for children born with single-ventricle cardiac defects. However, these children are at risk for serious long-term complications, some related to the lymphatic system. The lymphatic system consists of a widespread network of lymphatic vessels that drain and transport lymphatic fluid from the interstitial space back into the venous system. The largest lymphatic vessels return lymphatic fluid to the great veins of the neck and thorax. Increased filtration of interstitial fluid, insufficient drainage and/or anatomic lymphatic abnormalities can lead to lymphatic fluid accumulation.
In infants with a superior cavo-pulmonary connection (Glenn Operation) the lymphatics and veins of the neck and thorax drain against a higher pressure. Increased central venous pressure in both the Glenn and Fontan circulation is thought to lead to increased lymphatic production, compromised drainage and likely development or opening of anomalous lymphatic vessels. In some patients these changes lead to chylothorax, plastic bronchitis (PB) and/or protein-losing enteropathy (PLE). 1,2
Lymphangiography and T2-MRI make it possible to identify lymphatic abnormalities. (ref 3). Lymphatic abnormalities have been demonstrated both after Glenn and before Fontan surgery. A classification system was developed to grade these lymphatic changes (Figure).3 Types 1 and 2 were grouped together due to their similarity and anatomic location being supraclavicular only and were considered normal variants. Types 3 and 4 had progressive abnormalities with type 4 having supraclavicular, mediastinal and lung parenchymal T2 signals. When and how these lymphatic changes occur is not known. Lymphatic abnormalities relate to outcomes following Fontan operation. The greater the severity of the lymphatic abnormalities pre-Fontan was associated with poorer clinical outcomes including: higher mortality, longer length of stay, prolonged effusions and a 6-fold increase of developing early complications (structural failure, pump failure, effusions, chylothorax, PB) with type 3 or 4 lymphatic abnormalities.3,4 Lymphatic abnormalities can occur in fetal life in the form of nutmeg lung is some fetuses with single ventricle CHD.5 In today’s PAAD, Kristensen and colleagues6 retrospectively reviewed the T2-weighted MRIs obtained at a single center between June 2012 and October 2022 on 71 infants with single ventricle physiology prior to their Glenn procedure to determine if lymphatic abnormalities exist pre-Glenn and to determine if the severity of the lymphatic abnormality correlates with adverse outcomes including effusions chylothorax and mortality. The pre-Glenn images were categorized as type 1 to type 4 using the same classification system used to describe lymphatic changes post-Glenn and pre-Fontan operations. The authors found 42 (59%) of the patients had normal lymphatic patterns (type 1 and 2), 15 (21%) and 14 (20%) patients had type 3 and type 4 abnormalities respectively.6
Chylothorax at any point was increasingly present with an increasing grading of lymphatic abnormality (12% with type 1 or 2, 53% with type 3 and 71% with type 4). There was an increasing prevalence of death at any time with advancing grade of lymphatic abnormality pre-Glenn.
The cause of these lymphatic abnormalities in single ventricle patients and why some patients develop lymphatic complications (chylous effusion, PB, PLE) and negative overall outcomes (heart replacement, death) is unknown.
This study is the first to identify lymphatic abnormalities prior to Glenn operations in infants with single ventricles. Early identification may lead to better prevention or treatment of later lymphatic complications. New methods for treating lymphatic complications are being described and perfected, including catheter-based percutaneous fluoroscopy-guided embolization of leaking lymphatic vessels, thoracic duct decompression via catheter (discussed by this group – Monday June 12th PAAD) or by innominate vein turn-down and innovative medical management strategies.7-9 The presence of high-grade lymphatic abnormalities may help identify patients with higher post-operative risk and a greater need for close follow- up.
Significant limitations of the current study are selection bias and small sample size. Only patients referred for a pre-Glenn cardiac MRI and only those whose MRI included a lymphatic T2 -MRI protocol, indications not specified, were included. This is likely not representative of the entire population of infants with single ventricle CHD coming for Glenn operation. Sequential lymphatic imaging from in-utero through Fontan completion on all patients will determine frequency and progression of these abnormalities.
A good review article on this topic was published by RochéRodríguez M and DiNardo JA in 2022. 10
References
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2. Menon S, Chennapragada M, Ugaki S, Sholler GF, Ayer J, Winlaw DS. The Lymphatic Circulation in Adaptations to the Fontan Circulation. Pediatr Cardiol. Jun 2017;38(5):886-892. doi:10.1007/s00246-017-1576-y
3. Biko DM, DeWitt AG, Pinto EM, et al. MRI Evaluation of Lymphatic Abnormalities in the Neck and Thorax after Fontan Surgery: Relationship with Outcome. Radiology. Jun 2019;291(3):774-780. doi:10.1148/radiol.2019180877
4. Ghosh RM, Griffis HM, Glatz AC, et al. Prevalence and Cause of Early Fontan Complications: Does the Lymphatic Circulation Play a Role? J Am Heart Assoc. Apr 7 2020;9(7):e015318. doi:10.1161/jaha.119.015318
5. Saul D, Degenhardt K, Iyoob SD, et al. Hypoplastic left heart syndrome and the nutmeg lung pattern in utero: a cause and effect relationship or prognostic indicator? Pediatr Radiol. Apr 2016;46(4):483-9. doi:10.1007/s00247-015-3514-6
6. Kristensen R, Kelly B, Kim E, Dori Y, Hjortdal VE. Lymphatic Abnormalities on Magnetic Resonance Imaging in Single-Ventricle Congenital Heart Defects Before Glenn Operation. J Am Heart Assoc. Jun 20 2023;12(12):e029376. doi:10.1161/jaha.123.029376
7. Dori Y, Keller MS, Rome JJ, et al. Percutaneous Lymphatic Embolization of Abnormal Pulmonary Lymphatic Flow as Treatment of Plastic Bronchitis in Patients With Congenital Heart Disease. Circulation. Mar 22 2016;133(12):1160-70. doi:10.1161/circulationaha.115.019710
8. Smith CL, Dori Y, O'Byrne ML, Glatz AC, Gillespie MJ, Rome JJ. Transcatheter Thoracic Duct Decompression for Multicompartment Lymphatic Failure After Fontan Palliation. Circ Cardiovasc Interv. Jul 2022;15(7):e011733. doi:10.1161/circinterventions.121.011733
9. Hraska V, Hjortdal VE, Dori Y, Kreutzer C. Innominate vein turn-down procedure: Killing two birds with one stone. JTCVS Tech. Jun 2021;7:253-260. doi:10.1016/j.xjtc.2021.01.045
10. RochéRodríguez M, DiNardo JA. The Lymphatic System in the Fontan Patient-Pathophysiology, Imaging, and Interventions: What the Anesthesiologist Should Know. Journal of cardiothoracic and vascular anesthesia. Aug 2022;36(8 Pt A):2669-2678. doi:10.1053/j.jvca.2021.07.049