DIASTOLIC HEART FAILURE M Mohsen Ibrahim, MD Alexandria,
Proposed Criteria for Diastolic Heart Failure ESC Working Group (EHJ 1998) CHF signs/symptoms EF 45% Hemodynamic or echo evidence of diastolic dysfunction Slow isovolumic LV relaxation Slow early LV filling Reduced LV diastolic distensibility Increased LV chamber stiffness or muscle stiffness
Differences and Similarities Between HF- PSF and Reduced EF Heart Failure Differences Older More women Less CAD and MI More hypertension Smaller, thicker LV Similarities Race Diabetes Smoking Lipids Weight AF
Diastolic Heart Failure Molecular Mechanisms Cellular Calcium hemostasis Fibrosis Extracellular Sarcomeric proteins type
Processes Underlying Diastolic Dysfunction Hypertension Aging Atherosclerosis Diabetes Blood Vessels Hypertrophy Altered elastin & collagen Calcification Endothelial dysfunction Loss of compliance Myocardium Hypertrophy (LVH) Fibrosis Cellular dysfunction Ischemia Increased stiffness Impaired relaxation Diastolic Dysfunction Heart Failure with MMM Preserved Ibrahim - 2006 Systolic Function
Prevalence of Heart Failure with Preserved EF 80 78 Percent of Patients 60 40 20 51 EF 50% 43 EF 50% EF 45% 57 EF 50% 35 EF 50% 0 Framingham (N=73) Olmstead (N=137) CHS Prevalence (N=269) CHS Incidence (N=597) NHF Project (N=6,700)
1-year Outcomes in HF-PSF 50% 40% 30% 20% 10% 0% Deaths HF Rehospitalizations EF <40% EF >40% Dauterman et al: J Cardiac Failure 2001
Management of HF-PSF ESC guidelines 2005 No treatment has official indication to date Therapeutic guidelines of the ESC : «...largely speculative as limited data exist in patients with preserved LV systolic function or diastolic dysfunction (level of evidence C), patients being excluded from nearly all large controlled trials in heart failure..»
DIASTOLIC HEART FAILURE Management Treatment of underlying cause: - Hypertension. - CAD (? revascularization). Control of ventricular rate Restoration of sinus rhythm in AF. Releive pulmonary and systemic congestion. Delay progression and remodeling. New approaches.
DIASTOLIC HEART FAILURE MANAGEMENT Delay Progression and Remodeling RAS Blockade : - Candesartan : CHARM Preserved. - Perindopril : PEP-CHF. - Irbesartan : I- PRESERVE. Aldosterone receptor antagonists : - Eplerenone : TOPCAT ( in progress). Beta-adrenergic blockers: - Carvedilol :.SWEDIC- improved E/A ratio..op Clinic - decreased BNP - improved FC
Rationale for ARBs in HF-PSF AT-1 antagonism has beneficial effects on CV structure and function reversal of LVH improvement in diastolic and systolic function improvement in endothelial function positive effects on vascular compliance Outcome data show that ARBs reduce CV morbidity and mortality
CHARM-Preserved: Primary outcome CV death or CHF hospitalisation 30 25 20 15 10 % Placebo 366 (24.3%) 333 (22.0%) Candesartan 5 0 HR 0.89 (95% CI 0.77-1.03), p=0.118 Adjusted HR 0.86, p=0.051 0 1 2 3 3.5 years S. Yusuf et.al., Lancet, 2003
PEP-CHF ESC meeting. Barcelona-Sept.2006
DIASTOLIC HEART FAILURE Management New Approaches Pharmacologic : Drugs (investigational) Devices ( preclinical) -Passive diastolic assist device Gene Therapy( preclinical)
136 patient with DHF: One- half treated with statin. Hidekatsu Fukuta, MD; David C. Sane, MD; Steffen Brucks, MD; William C.. Little, MD (Circulation 2005. )
Statins Benefit in HF : Possible Mechanisms Slow progression of ASO. Reduce atrial and vent arrhythmias. Improve endothelial function. Reduce aortic stiffness. Reduce inflammation. Reduce oxidative stress. Reduce LV hypertrophy. Prevent LV remodeling. Reduce neurohormonal activation.
DIASTOLIC HEART FAILURE Management New Aproaches Drugs ( Investigational) - Alagebrium ( ALT-711): Breaks AGE cross-links between proteins Arterial stiffness DIAMOND trial : -NYHA class improved -LVM decrease -Improve LV filling -Caldaret (MCC-135) Improve SR calcium uptake
Conclusions HF-PSF is frequent HF-PSF is associated with high CV event rate Treatment remains empirical Preliminary evidence indicates that AT-1 blockade may be beneficial New therapeutic approaches are under investigation