A Novel Strategy for the Mechanical Subpulmonary Support in Failing Fontan Patients

Abstract

Background The number of single ventricle patients undergoing Fontan palliation and surviving to adulthood worldwide has steadily increased in recent years. Nevertheless, the Fontan circulation is destined to fail. Ultimately, heart transplantation (HTx) remains the definitive treatment option. Due a shortage of organs, mechanical circulatory support in the form of ventricular assist devices (VADs) is widely used to bridge heart failure patients to HTx, but these devices have been mainly developed to address the needs of normal anatomies. A novel venous cannula has been developed as part of the EXCOR® VAD to provide subpulmonary support in these patients. Its clinical application is investigated in the “Registry to Assess the Safety and Feasibility of the Subpulmonary Support with the Novel Venous Cannula in Patients with Failing/Absence of the Right Heart” (RegiVe study, NCT04782232).

Methods RegiVe is a multicenter, international, observational, prospective, non-randomized registry aiming to collect the routine clinical data of up to 20 patients. The primary endpoints address device performance and safety, while the secondary endpoints target organ status and overall safety (according to the Interagency Registry for Mechanically Assisted Circulatory Support – INTERMACS – definitions). Data analysis will be performed by means of descriptive statistics.

Results RegiVe has received the favorable opinion of an independent ethics committee and enrollment has recently started.

Conclusion RegiVe is the first study evaluating the use of a medical device specifically developed for subpulmonary support of failing Fontan patients. The study will provide important insight and further information on this cohort and help to improve a dedicated VAD strategy.

Keywords

circulatory assist devices - congenital heart disease - transplantation - heart

Note

The study concept has been presented at the 50th Annual Meeting of the German Society for Thoracic and Cardiovascular Surgery (DGTHG); online; February 26^th to 28^th, 2021 [Menon et al, Thorac Cardiovasc Surg 2021;69(S 01)].

Author's Contribution

O. M., F. D. R., and A. K. M. devised the medical rationale for this novel treatment option. E. D. S., T. S., K.-J. S., and A. K. M. elaborated the conceptual study design. The expert panel “European EXCOR® Pediatric Investigator Group” (EEPIG) contributed with intensive discussion and mutual agreement. E. D. S. prepared the manuscript, and all other authors contributed by thorough manuscript review. The authors thank Mr. Samuel Alberman for editing the manuscript.

Publikationsverlauf

Eingereicht: 02. Juni 2022

Angenommen: 05. September 2022

Artikel online veröffentlicht:
11. November 2022

• References

• 1 Rychik J, Atz AM, Celermajer DS. et al; American Heart Association Council on Cardiovascular Disease in the Young and Council on Cardiovascular and Stroke Nursing. Evaluation and management of the child and adult with Fontan circulation: a scientific statement from the American Heart Association. Circulation 2019;140:CIR0000000000000696
• 2 Clift P, Celermajer D. Managing adult Fontan patients: where do we stand?. Eur Respir Rev 2016; 25 (142) 438-450
• 3 Poh CL, d'Udekem Y. Life after surviving Fontan surgery: a meta-analysis of the incidence and predictors of late death. Heart Lung Circ 2018; 27 (05) 552-559
• 4 Elder RW, Wu FM. Clinical approaches to the patient with a failing Fontan procedure. Curr Cardiol Rep 2016; 18 (05) 44-47
• 5 Kenny LA, DeRita F, Nassar M, Dark J, Coats L, Hasan A. Transplantation in the single ventricle population. Ann Cardiothorac Surg 2018; 7 (01) 152-159
• 6 Riggs KW, Broderick JT, Price N, Chin C, Zafar F, Morales DLS. Transplantation for congenital heart disease: focus on the impact of functionally univentricular versus biventricular circulation. World J Pediatr Congenit Heart Surg 2021; 12 (03) 352-359
• 7 Bryant III R, Morales D. Overview of adult congenital heart transplants. Ann Cardiothorac Surg 2018; 7 (01) 143-151
• 8 Reid CS, Kaiser HA, Heinisch PP, Bruelisauer T, Michel S, Siepe M. Ventricular assist device for Fontan: who, when and why?. Curr Opin Anaesthesiol 2022; 35 (01) 12-17
• 9 Buratto E, Shi WY, Ye XT, Konstantinov IE. Ventricular assist devices for the failing univentricular circulation. Expert Rev Med Devices 2017; 14 (06) 449-459
• 10 Griselli M, Sinha R, Jang S, Perri G, Adachi I. Mechanical circulatory support for single ventricle failure. Front Cardiovasc Med 2018; 5: 115
• 11 Villa CR, Alsaied T, Morales DLS. Ventricular assist device therapy and Fontan: a story of supply and demand. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2020; 23: 62-68
• 12 Prêtre R, Häussler A, Bettex D, Genoni M. Right-sided univentricular cardiac assistance in a failing Fontan circulation. Ann Thorac Surg 2008; 86 (03) 1018-1020
• 13 Moosmann J, Dittrich S, Purbojo A, Cesnjevar R. RVAD implantation in a Fontan patient with protein-losing enteropathy as a bridge to transplant: Prêtre modification. J Card Surg 2020; 35 (07) 1721-1724
• 14 Nathan M, Baird C, Fynn-Thompson F. et al. Successful implantation of a Berlin heart biventricular assist device in a failing single ventricle. J Thorac Cardiovasc Surg 2006; 131 (06) 1407-1408
• 15 Valeske K, Yerebakan C, Mueller M, Akintuerk H. Urgent implantation of the Berlin Heart Excor biventricular assist device as a total artificial heart in a patient with single ventricle circulation. J Thorac Cardiovasc Surg 2014; 147 (05) 1712-1714
• 16 Michel SG, Menon AK, Haas NA, Hörer J. Cavopulmonary support with a modified cannulation technique in a failing Fontan patient. Interact Cardiovasc Thorac Surg 2022; 35 (02) ivac090
• 17 McCormick AD, Schumacher KR. Transplantation of the failing Fontan. Transl Pediatr 2019; 8 (04) 290-301
• 18 Al Balushi A, Mackie AS. Protein-losing enteropathy following Fontan palliation. Can J Cardiol 2019; 35 (12) 1857-1860
• 19 Téllez L, Rodríguez-Santiago E, Albillos A. Fontan-associated liver disease: a review. Ann Hepatol 2018; 17 (02) 192-204
• 20 Daniels CJ, Bradley EA, Landzberg MJ. et al. Fontan-associated liver disease: proceedings from the American College of Cardiology Stakeholders Meeting, October 1 to 2, 2015, Washington DC. J Am Coll Cardiol 2017; 70 (25) 3173-3194
• 21 Ybarra AM, Khanna G, Turmelle YP. et al. Heterogeneous outcomes of liver disease after heart transplantation for a failed Fontan procedure. Pediatr Transplant 2021; 25 (08) e14094
• 22 Assenza GE, Graham DA, Landzberg MJ. et al. MELD-XI score and cardiac mortality or transplantation in patients after Fontan surgery. Heart 2013; 99 (07) 491-496
• 23 Grimm JC, Magruder JT, Do N. et al. Modified Model for End-Stage Liver Disease eXcluding INR (MELD-XI) score predicts early death after pediatric heart transplantation. Ann Thorac Surg 2016; 101 (02) 730-735
• 24 Yang JA, Kato TS, Shulman BP. et al. Liver dysfunction as a predictor of outcomes in patients with advanced heart failure requiring ventricular assist device support: use of the Model of End-stage Liver Disease (MELD) and MELD eXcluding INR (MELD-XI) scoring system. J Heart Lung Transplant 2012; 31 (06) 601-610
• 25 Elder RW, McCabe NM, Hebson C. et al. Features of portal hypertension are associated with major adverse events in Fontan patients: the VAST study. Int J Cardiol 2013; 168 (04) 3764-3769
• 26 Elder RW, McCabe NM, Veledar E. et al. Risk factors for major adverse events late after Fontan palliation. Congenit Heart Dis 2015; 10 (02) 159-168
• 27 Rodriguez DS, Mao C, Mahle WT. et al. Pretransplantation and Post-transplantation liver disease assessment in adolescents undergoing isolated heart transplantation for Fontan failure. J Pediatr 2021; 229: 78-85
• 28 Padalino MA, Chemello L, Cavalletto L, Angelini A, Fedrigo M. Prognostic value of liver and spleen stiffness in patients with Fontan associated liver disease (FALD): a case series with histopathologic comparison. J Cardiovasc Dev Dis 2021; 8 (03) 30
• 29 Murtuza B, Hermuzi A, Crossland DS. et al. Impact of mode of failure and end-organ dysfunction on the survival of adult Fontan patients undergoing cardiac transplantation. Eur J Cardiothorac Surg 2017; 51 (01) 135-141
• 30 Márquez-González H, Hernández-Vásquez JG, Del Valle-Lom M. et al. Failures of the Fontan system in univentricular hearts and mortality risk in heart transplantation: a systematic review and meta-analysis. Life (Basel) 2021; 11 (12) 1363
• 31 Karamlou T, Hirsch J, Welke K. et al. A United Network for Organ Sharing analysis of heart transplantation in adults with congenital heart disease: outcomes and factors associated with mortality and retransplantation. J Thorac Cardiovasc Surg 2010; 140 (01) 161-168