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

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

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

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

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

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

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

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

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

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

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

CRT reverses LV remodeling t Sutton MG Circulation 2003

Woo G W et al Journal Int Card Electroph 2005

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

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

813 pts (26%women) CARE-HF Study

Cleland JGF NEJM 2005

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

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

Linde C JACC pts NYHA class I or II

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

141 pts Yu CM Circulation 2005

Few observational studies have shown that ………….

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Placebo E2 van Eickels M Circulation 2001 TAC Transverse Aortic Constriction

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

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.

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