1. Pulmonary Arterial Hypertension in CHD patients : medical approach Milan , October 8th, 2011 Giorgio Serino Department of Internal Medicine IRCCS Policlinico San Donato 2007r2011

4. PAH : istopathological features Intra-acinar pulmonary arteria Intimal thickening Medial Hyperthrohy Adventitial thickening

7. Prevalence CHD in patients of different age groups Marelli AJ. 2007

15. PAH: A Rapidly Evolving Disease I Preclinical/ No Symptoms II Symptomatic / Stable III Progression / Declining Level Time Years Months NYHA I: No limits to physical activity NYHA II Some limitation NYHA IV Severe limitation Symtoms at rest NYHA III Marked limitation JL Vachiery. Dept of Cardiology ULB Erasmus Hospital Brussel Pulm. pressure Cardiac output Therapeutic window RV function

16. Plexiform lesion Focal proliferation of endothelial channels Myofibroblasts SMC Connective matrix Thrombosi in situ

17. Evolution in pulmonary vascular disease in the young Haworth SG (1995) Exp Physiol 80(5) PVR ?

18. … post-operative PAH has worse survival than Eisenmenger’s S. in children . Haworth SG et al.Heart 2009

19. Reversible pulmonary vascular disease 15 mounths after transcatheter closure of ASD in 215 Pts A : reduction doppler-derived PAPs B : normalization of PAPs Yong G et al.2009

20. Eur Respir Rev 2009

21. Eur Respir Rev 2009

22. Survival by diagnosis for adult with Eisenmenger s. and with iPAH Hopkins et al.2002; Am J Cardiol 89(1)

23. Non-transplation survival in patients with E.S., iPAH and other ACHD Trulock EP et al. 2004 J Heart Lung Transplant 23(7)

24. Survival by diagnosis for adult with PAH-CHD and with A -PAH McLaughlin VV et al Circulation 2009

25. TARGETED THERAPY Adapted from National Pulmonary Hyperthension Center of UK and Ireland - Thorax 2008 Management algorithm for Eisenmenger patients

30. Circulation-2011;123

31. Disturbed vascular function in PAH adapted from Humbert M et al.2004

32. NEJM-2005 Int J Cardiol 2008 Circulation 2006 NEJM-2005

33. PAH treatments : a historical overview Adapted from Tapson VF. CHD-PAH Bosentan

34. Targeted Therapy

35. J Heart Lung Transplant.2006

37. Van Loon RL et al.Am Heart J 2007;154(4)

38. Earlier treatment (NYHA class I-II) would allow both improved quality of life and potentially improved mortality. Steven D.N.- Medscape Cardiology 2007

40. Combination Therapy

41. J Heart Lung Transpl 2007; 26 n°5

42. Combination Therapy Haworth SG et al.Heart 2009

51. N=7

52. … .grazie. Ambulatorio Studio e Terapia dell’Ipertensione Polmonare e del Microcircolo [email_address]

53. www.escguideline.org