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

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

7. 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 CRT

8. Alaeddini J. PACE 2008 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%

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

10. 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. MIRACLE study

11. EFFECT OF CRT ON EFFICACY END POINTS MIRACLE study 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 Woo G W et al J Int Card Electroph 2005 Time to first HF hospitalization Women Men

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

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

17. Cleland JGF NEJM 2005

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

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

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

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

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? Bleeker GB PACE 2005 Response based on improvement in NYHA class

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

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

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

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

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 Ghali JK JACC 2003 2708 pts(28%omen Randomized to Bucindolo or Placebo

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

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

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

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

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

42. Jessup, M. J Thorac Cardiovasc Surg 2004 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.

43. 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 Conclusioni