Single Ventricle BUT Multiple PH treatment in Single Ventricule - PowerPoint PPT Presentation

3/9/2019 « Single » Ventricle BUT Multiple… PH treatment in Single Ventricule • Ventricular function: LV? RV? • Atrial pressure : AV valve ? • Pulmonary circulation ? Marilyne Lévy, Necker- Paris - France UCSF from 2016 to 2019 Fontan circulation From 10 to 1 restriction • 1971 : Tricuspid Atresia • Limited indications • 10 restrictions NO RIGHT V – Age > 4 years – mPAP < 15mmHg – PVR < 3 WU – No PA dystorsion Technical improvement – Normal venous return TCPC – No arythmia Extracardiac tube – No right atrial enlargement Fenestration – No AV regurgitation – No ventricular dysfunction pulmonary circulation – No previous surgical complications precapillary PH or post-capillary PH ( Fontan’s Decalogue ) Thorax. 1971 May;26:240–248 1

3/9/2019 The objective Early and Late outcome in 124 pts • To maintain low PVR PREOPERATIVE MEAN PA PRESSURE : END DIASTOLIC 18 mmHg>>>15mmHg – Banding we never now : Too high or too low VENTRICULAR PRESSURE : 12 mmHg – Blalock shunt : pulmonary artery distorsion – Natural pulmonary stenosis ≤ 18 mmHg Sa02 > 19 mmHg SaO 2 > 85% QP/QS > 2 90 85 Overload 10 yrs QP/QS 2 3 Mario Cazzaniga Rev Esp Cardiol. 2002;55:391-421 Risk : Normal PAP and PV Reactivity Targeted treatments on PVR PAP < 15mmHg PDE5 inhibitors 50% distal lesions NO iloprost eNOS ERA Levy et al. J Thorac Cardiovasc Surg. 2003;125:1083-90 2

3/9/2019 PH drugs and SV Targeted treatments on PVR PDE5 inhibitors NO • Sildenafil et Fontan : 41 articles (entre 2006 et 2019) Many studies but difficult to analyze • Bosentan et Fontan : 18 articles (entre 2005 et 2019) iloprost ERA • Prostanoïdes et Fontan : 6 articles (entre 2003 et 2019) Essentially VO2 Spain Registry . Maria Jesus Del Cerro Results ? Inclusion of patients 2009-2018 PH biventricular Univentricular P Médic N etude FU Resultat Hebert 2014 Bosentan 45 Pic VO2 14 sem + 2ml/kg/min 600 Schuuting 2013 Bosentan 42 Exercice 6 mois 0 500 Ovaert 2009 Bosentan 10 CF, Sa02 16 sem + SaO2 Kouatli 1997 Enalapril 20 Exercice 20 sem 0 400 Goldberg 2012 Sildenafil 28 Fonction VU 6 sem ≠ 0 300 Giardini 2008 Sildenafil 27 Exercice 1 jour Augm VO2 200 Van de Bruaene 2014 Sildenafil 10 KT exercice 1 jour Augm IC Hager 2014 Sildenafil 36 Exercice 1 jour Augm VO2 100 Rhodes 2013 Iloprost 18° Exercice 2 jours Augm VO2 0 ° 10/18 effets secondaires (bronchospasme) 2010 2011 2012 2013 2014 2015 2016 2017 2018 Oldenburger et al. Cardiology in the Young 2016;26:842-50 3

3/9/2019 When do we need to treat? What for ? • Before surgery ? • Decrease PAP ? • During surgery ? • Improve FC ? • Long term ? • Improve exercise capacity ? • Failing Fontan? • Decrease mortality ? Before surgery Before surgery • Testing PVR before Fontan circulation • Testing PVR before Fontan circulation YES • In patients with « limit » PAP in order to YES operate patient with contrindication? – Mori H et al. Int J Cardiol 2016;221:122-7 • Preop Sildenafil reduced PVR ? – Tran S et al. Pediatr Cardiol 2018;39:1572-80 • mPAP > 16 Need of preoparative use of sildenafil was associated with higher morbidity - NO 4

3/9/2019 During surgery Sildenafil postop after Fontan • In order to facilitate the post-operative course • Most team use vasodilators in ICU • Very few published studies Tunks RD et al. Pediatr Crt Care Med 2014;15:28-34 Sildenafil postop after Fontan After surgery • 16 pts Sildenafil + NO • 32 patients without Mendoza A et al. Cardiol Young 2015;25:1136-40 • 19 pts Sildenafil IV • 84 patients without • To improve PVR? • To improve FC and excercise capacity? Collins JLG et al. Pediatr Cardiol 2017;38:1703-8 Pleural effusion NS • Only in Failing Fontan? Ventilation time NS Lenght ICU NS Lenght hospital stay NS 5

3/9/2019 After surgery After surgery Sudye Year TT Npts FU Conclusion • 24 Fontan patients : PRV > 2 UW/m 2 Hebert 2014 Bosentan 75 3 months FC; VO2 • 8 children, 8 adolescents, 8 adults evaluated Schuuring 2013 Bosentan 42 6-9 months NS before and 6 months after treatment with ERA Ovaert 2009 Bosentan 10 4 months NS Kouatli 1997 Enalapril 21 3 months NS Goldberg 2012 Sildenafil 28 6 weeks SV function PVRi Cardiac Index VO2 max Hager 2014 Sildenafil 36 1 day VO2 Before After Before After Before After Rhodes 2013 Iloprost inh 18 2 days VO2 Children 2.3 1.9 Adol 2.3 1.7 2.6 3.6 25 28 Meta-analysis Adults 2.8 2.1 2.1 2.8 Oldenburger NJ et al. Cardiol Young 2016;26:842-50 CONCLUSION : Bosentan, Sildenafi and iloprost may improve exercise capacity Agnoletti G et al. J Thorac Cardiovasc Surg 2017;153:1468-75 at the short term in Fontan patients BUT RESLUS NEED TO BE INTERPRETED CAREFULLY Sildenafil improves After surgery exercise hemodynamics in Fontan patients. N = 10 Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation PAP The TEMPO (Treatment With Endothelin Receptor Antagonist in Fontan Patients, a Randomized, Placebo-Controlled, Double-Blind Study Measuring Peak Oxygen Consumption) Study Fontan at 4 years. Mean age 20 y – Bosentan 3 months 28.7 to 30.7 PVRi Van De Bruaene A1, La Gerche A, Claessen G, De Meester P, Devroe S, Gillijns H, Bogaert J, Claus P, Heidbuchel H, Gewillig M, Budts W Circ Cardiovasc Imaging. 2014;7:265- 73. Hebert A et al. Circulation 2014;130:2021-30 6

3/9/2019 Failing Fontan Failing Fontan • 13 failing Fontan – 3 protein-losing enteropathy – 4 bronchial cast – 2 severe cyanosis after fenestration – 2 prolonged chylous effusion – 1 take down – 1 arythmia and end stage cardiac failure • 2 years Sidenafil • All improved BUT 5 patients had concomittent fenestration Reinhardt et al. Cardiol Young 2010;20:522-5 Morchi GS et al. Congenit Heart Dis 2019;4:107-111 Decreased aerobic capacity in Fontan What about Long Term Fontan? patients 52 patients At late follow up (median 10 years, range 1 to 26 years) • Few publications on VO 2 • Long term results are very poor Fredriksen P et al. Heart Heart. 2001 Mar; 85(3): 295–299 7

3/9/2019 Late Fontan PDE5 in adolescent after Fontan Palliation and Quality of life Phase I/II Muticenter Investigation. Goldberg JG et al. Am Heart J 2017;188:42-52 • 30% free of events à 20 ans Rychik J, Goldberg DJ.Circulation 2014;130:1525-8 d’Udekem Y et al. Circulation 2014;130:32-8 Rychic et al.Pediatr Cardiol. 2012; 33:1001–1012 Kiesewetter et al. Heart 2007;93: 579–584 Paris 1990-2018 – Poor results Patients > 30 years old • 344 TCPC – 160 FU 10-35yrs (med 20) • 49 patients – 57 lost : Alive? Dead? • 5 deaths • 110 adults FU more than 20 years FU • 5 tranplantations 35% Severe events • 4 Tx list* – Death 6* – Tx 5 • 3 Strokes 72% 36% 53% – Tx list 5** • 9 FC 2 18% – NYHA 3 24 – 3 non operated patients – Severe arythmia 13 32% in FC 2or3 – Neurologic cpcs 5 – 1 IVC valuvulation – Treated arythmia 21 • 7 FC 2-3 (fistulae; arythmia) ** liver cancer * Cirrhosis at autopsy * hepatocarcinoma 8

3/9/2019 Long term Fontan Long term Fontan • Loss of pulsatile pulmonary blood flow after the Fontan procedure has been suggested to • Loss of pulsatile pulmonary blood flow after increase PVR through vascular remodeling the Fontan procedure has been suggested to Zongtao Y et al. J Thorac Cardiovasc Surg. 2010;58:468–472 Protection of increase PVR through vascular remodeling Henaine R et al. J Thorac Cardiovasc Surg. 2013;146:522-9 • Severe intimal damage at autopsy that Zongtao Y et al. J Thorac Cardiovasc Surg. 2010;58:468–472 pulmonary Henaine R et al. J Thorac Cardiovasc Surg. 2013;146:522-9 correlate with age at death and duration of • Severe intimal damage at autopsy that endothelial function Fontan circulation correlate with age at death and duration of Ridderbos FJ et al. Heart Lung Transplant 2015;34:404-13 from birth Fontan circulation Ridderbos FJ et al. Heart Lung Transplant 2015;34:404-13 Our attitude in Paris Our attitude in Paris • 344 Fontan patients • Treatment in the perioperative course • Since 2002 almost all the patients have • No preventive treatment fenestrated fontan (extracardiac tube) • In case of complications : sildenafil occluded 6 months later if possible • Except aorto-pulmonary collaterals, all receive • According to my talk, illogical…. sildenafil in the post-operative course • We need to improve the management of this • Sildenafil is not continued population according to the long-term results 9

3/9/2019 Conclusion What Future ? • even with the technical adapations and use of • PVR are crucial before TCPC PH treatments • PVR are crucial after TCPC • Fontan circulation is not a good option (arythmia, liver, brain, kidney..) • No real effect of PH treatments ? • Less than 20% in FC 2 at the age of 30!!! • What about lack of pulsatility ? • Other options? What Future ? Next generation PH training • Less than 20% in FC 2 at the age of 30!!! • Other options? To « create » the physiological circulation Pneumologist Neonatologist 1h/week ? genticien Cardiologist 10

3/9/2019 Next generation Cardiologist Neonatologist Pneumologist Thank you for your attention Fontan et dysfonction endothéliale NO caused a significant drop of mean PVRI late after Fontan (* P =0.016). Thank you for your attention Khambadkone S et al. Circulation. 2003;107:3204-8 Perte de pulsatilité et altération de la réponse endothéliale Kurotobi S et al. J Thorac Cardiovasc Surg. 2001;121:1161-8 11