Tenth International Symposium HEART FAILURE & Co. CARDIOLOGY SCIENCE UPDATE

1. Tenth International Symposium HEART FAILURE & Co. CARDIOLOGY SCIENCE UPDATE FEMALE DOCTORS SPEAKING ON FEMALE DISEASES Milano 9 - 10 aprile 2010 CRT: vi è un vantaggio maggiore nelle donne? M.Cristina Porciani FIRENZE

2. Heart Failure affects 5.3 millions Americans Nearly 50% of these are women Heart failure contributes 35% of the total female cardiovascular disease mortality Despite this fact, HF in women remains a poorly recognized syndrome and has not received the same public awareness as coronary artery disease

3. Where Are All the Women With Heart Failure? Lindenfeld J JACC 1997

4. Prevalence rates of congestive heart failure (CHF) among Framingham Heart Study subjects, by gender and age

5. Prevalence and Mortality from Congestive Herat Failure During years 2004 and 2005 based on Medicare Database Alaeddini J PACE 2008

6. Patients who were admitted with diagnosis of congestive heart failure for the years 2002 to 2004 based on Medicare Database Alaeddini J PACE 2008

7. CRT CRT has become a significant part of the management of patients with HF Several large-scale studies demonstrated significant improvement in multiple endpoints, including quality of life , hospitalization rate and survival in patients with advanced HF

8. Gender Disparity in the Use of CRT in the United States Females underwent CRT-PM or CRT-D implantation 2002 2003 2004 25% 26% 27% Alaeddini J. PACE 2008

9. What is the response to CRT in women ? ► Analysis of previous large CRT Trials ► Few studies addressing this issue

10. MIRACLE study The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) was a prospective, randomized, double-blinded study A total of 453 pts ( 32%women) randomized to either CRT or a control group.

11. MIRACLE study EFFECT OF CRT ON EFFICACY END POINTS Abraham WT NEJM 2002

12. CRT reverses LV remodeling t Sutton MG Circulation 2003

13. Woo G W et al Journal Int Card Electroph 2005

14. Analysis of the MIRACLE Study Women Men Time to first HF hospitalization Woo G W et al J Int Card Electroph 2005

15. Analysis of the MIRACLE Study Women Men Time to first HF hospitalization or death Woo G W et al Journal Int Card Electroph 2005

16. CARE-HF Study 813 pts (26%women)

17. CARE-HF Study Cleland JGF NEJM 2005

18. MADIT CRT 1820 pts 24% women NYHA class I or II

19. MADIT CRT Risk of Death or Heart Failure, According to Selected Clinical Characteristics Moss AJ NEJM 2009

20. 610 pts NYHA class I or II Linde C JACC 2008

21. REVERSE Study Effect of CRT on LVESVI 610 pts NYHA class I or II Linde C JACC 2008

22. 141 pts Yu CM Circulation 2005

23. Few observational studies have shown that ………….

24. Does a Gender Difference in Response to C RT Exist? Bleeker GB PACE 2005

25. Does a Gender Difference in Response to C RT Exist? Bleeker GB PACE 2005

26. Does a Gender Difference in Response to C RT Exist? Response based on improvement in NYHA class Bleeker GB PACE 2005

27. The Impact of Age and Gender on Cardiac Resynchronization Therapy Outcome Baseline Characteristics of Patients Stratified by Gender Zardkoohi O et al PACE 2007

28. The Impact of Age and Gender on Cardiac Resynchronization Therapy Outcome Hospitalization for heart failure and/or death free survival curve Zardkoohi O et al PACE 2007

29. The Impact of Age and Gender on Cardiac Resynchronization Therapy Outcome When stratified by the etiology of the underlying cardiomyopathy, ischemic women appear to have a worse long-term outcome than all other groups Zardkoohi O et al PACE 2007

30. CRT: Gender Related Differences in Left Ventricular Reverse Remodeling Lilli A PACE 2007 195pts (23%women)

31. CRT: Gender Related Differences in Left Ventricular Reverse Remodeling ◄ ◄ Lilli A PACE 2007

32. CRT: Gender Related Differences in Left Ventricular Reverse Remodeling Lilli A PACE 2007

33. CRT: Gender Related Differences in Left Ventricular Reverse Remodeling Lilli A PACE 2007

34. CRT Trials and observational studies show discordant results However a gender related difference in response to CRT seems to occur It is not surprising since there are many reasons why male and female hearts are not the same

36. Gender Differences in Advanced HF: Insights From the BEST Study Baseline Clinical Characteristics by Gender 2708 pts(28%omen Randomized to Bucindolo or Placebo Ghali JK JACC 2003

37. Heart Failure in Women :A Need for Prospective Data Left ventricular Ejection Fractionin Women and Men with Congestive Heart Failure Hsich EM JACC 2009

38. Sex-Related Differences in Myocardial Remodeling Myocardial Response to Pressure Overload Women Men Piro M et al JACC 2010

39. Left ventricular geometry and function in patients with aortic stenosis: gender differences Echocardiographic characteristics of patients with aortic stenosis Kostkiewicz M Int J Cardiol 1999

40. Placebo E2 TAC Transverse Aortic Constriction van Eickels M Circulation 2001

41. Myocyte Death in the Failing Human Heart Is Gender Dependent Guerra S Circulation Research 1999

42. Gender-related survival rates and how they might be influenced by different pathophysiologic mechanisms in men and women. LVH,left ventricular hypertrophy; RAS, renin-angiotensin system; SNS, sympathetic nervous system. Jessup, M. JThorac Cardiovasc Surg2004

43. Conclusioni CRT: vi è un vantaggio maggiore nelle donne? Al momento attuale la scarsa rappresentazione delle donne negli studi sulla terapia cardiaca resincronizzante fa si che ancora non vi siano chiare evidenze su un loro maggior beneficio tuttavia Le particolari caratteristiche dello scompenso cardiaco ed in particolare i diversi meccanismi che modulano il rimodellamento ventricolare nelle done rappresentano importanti presupposti per una loro migliore risposta