Evidence Based Management of Heart Failure with Normal/Preserved Ejection

Fraction

Moises Auron, MD FAAP FACPMoises Auron, MD FAAP FACP

Hospital MedicineHospital Medicine

October 2009October 2009

Diagnostic Criteria

• Symptoms and signs compatible with heart failure

• Left ventricular ejection fraction >50%

• Exclusion of severe valvular disease and pericardial disease

Hunt SA et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult. Circulation 112: e154–e235

Epidemiology

• 20% to 60% of patients with HF

• Increasing prevalence

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Owan T, et al. NEJM. 2006;355:251-9

Pathophysiology

• Reduced ventricular compliance (myocardial stiffness) and fluid retention

• Abnormal renal sodium handling and arterial stiffness, in addition to myocardial stiffness

• The majority of patients have a history of hypertension

• Most of the patients have evidence of LVH on echocardiography.

• More frequent in elderly women

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Pathophysiology

Aurigemma GP. NEJM. 2004;351:1097-105.

Pathophysiology

Cliger C, et al. AJGC. 2006;15:50–57

Aurigemma GP, et al. Circulation 2006; 113: 296–304

Systolic HF

Normal heart

Diastolic HF

Pathophysiology

Single syndrome hypothesis

Ouzounian M. Nature Clin Pract Cardiovasc Med. 2008; 5(7): 375-86

Aging and HF with preserved EF

• Decrease in the elastic properties of the heart and great vessels• Subsequent increase in SBP an increase in myocardial stiffness. • Decrease in ventricular filling due to:

– structural changes in the heart (fibrosis)– decline in relaxation and compliance. – decrease in beta-adrenergic receptor density – decline in peripheral vasodilator capacity

• Elderly patients associated disorders – CAD– DM– aortic stenosis– Atrial fibrillation– Obesity), – Sex-specific women are more susceptible.

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Ouzounian M. Nature Clin Pract Cardiovasc Med. 2008; 5(7): 375-86

Myocardial disorders associated with HF and normal LVEF

• Restrictive cardiomyopathy

• Obstructive hypertrophic cardiomyopathy

• Nonobstructive hypertrophic cardiomyopathy

• Infiltrative cardiomyopathies

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Diastolic CHF?

Understanding nondiastolic mechanisms of Heart Failure with Normal Ejection Fraction may provide further answers and, more importantly, lead to more therapeutic advances.

Myocardial systolicVentricular

Vascular

Renal

Neurohumoral

Non-CV

Normal EF Heart Failure

Bench T, et al. Current Heart Failure Reports 2009, 6:57–64

Non-diastolic mechanisms

• Volume overload

• Venoconstriction/volume redistribution

• Ventricular vascular coupling abnormalities

• Chronotropic incompetence

• Endothelial dysfunction

Bench T, et al. Current Heart Failure Reports 2009, 6:57–64

Volume overload

Maurer MS. J. Am. Coll. Cardiol. 2007;49;972-981

Hypertension and heart failure in the setting of normal EF

Cliger C, et al. AJGC. 2006;15:50–57

Prolonged QRS and mortality

Hummel SL, et al. J Cardiac Fail 2009;15:553-60.

N=872

Prolonged QRS and mortality

Hummel SL, et al. J Cardiac Fail 2009;15:553-60.

N=872

Diagnosis

• Slow rate of ventricular relaxation is slowed• Elevated LV filling pressure in a patient with

normal LV volumes and contractility.• Clinical diagnosis based on the finding of typical

symptoms and signs of HF in a patient who is shown to have a normal LVEF and no valvular abnormalities (aortic stenosis or mitral regurgitation, for example) on echocardiography.

• Doppler echocardiography (TTE) • BNP levels in addition to TTE improve diagnostic

accuracy.

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Echocardiography

Aurigemma GP. NEJM. 2004;351:1097-105.

E = early filling

A = atrial contraction

Echocardiography

Bursi F, et al. JAMA 2006;296:2209-2216.

Echocardiography

Sm = peak systolic velocity

septal side of the mitral valve annulus or base.

Em = peak early diastolic velocityAm = peak atrial contraction velocity

Sanderson JE. Prog Cardiov Dis. 2006;49(3): 196-206

Systolic dysfunction with normal EF

• New doppler echocardiography techniques reveals abnormal ventricular function particularly in the long axis.

• Ejection is relatively preserved because of increased radial function.

Sanderson JE. Prog Cardiov Dis. 2006;49(3): 196-206

Myocardial strain and torsion: Speckle-tracking echocardiography

Circumferential strain from the apical LV level in a healthy individual. Homogenous circumferential distribution of normal systolic strain.

Circumferential strain at the LV apical level in a patient with a LAD-related MI. Reduced systolic shortening (strain) in the anterior, septal, andinferior segments, with marked postsystolic contraction (white arrows). Early septal systolic stretching indicating dyskinesis (red arrow). Normal contraction is seen in the lateral segments.

Edvardsen T. Prog Cardiov Dis. 2006;49(3): 207-14.

Doppler tissue imaging – validated with MRI

“The present study has shown that DTI can quantify LV torsional deformation over time. This novel method may facilitate noninvasive quantification of LV torsion in clinical and research settings.”

Notomi Y. Circulation. 2005;111:1141-1147.)

Cardiac MRI vs. Echocardiography

Rademakers FE. Prog Cardiov Dis. 2006;49(3): 215-27.

Prognosis

HR 1.13; 95%CI 0.94-1.36; P=0.18

Owan TE. NEJM. 2006;355:251-9.

Bhatia RS. NEJM. 2006;355:260-9.

Prognosis

Somaratne JB. Eur J Heart Fail. 2009;11:855-62

Treatment

• Limited evidence. • Use of same drugs as for systolic CHF

justified due to co-morbid conditions – Atrial fibrillation, hypertension, diabetes

mellitus, and coronary artery disease

• The management of these patients is based on the control of physiological factors (blood pressure, heart rate, blood volume, and myocardial ischemia)

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Completed trials for HF with preserved EF

Lam CSP. Ann Acad Med. 2009;38(8): 663-666.

Hong Kong trial• ACE vs. ARB vs. diuretics

Yip GWK, et al. Heart 2008;94;573-580.

VALIDD Trial: supporting antihypertensive TxValsartan In Diastolic Dysfunction

Lowering blood pressure improves diastolic function irrespective of the type of antihypertensiveagent used.

Solomon SD. Lancet 2007; 369: 2079–87

OPTIMIZE – HF: Betablockers

Hernandez, et al. JACC. 2009 Jan 13;53(2):184-92

Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure

OPTIMIZE – HF: Betablockers

Hernandez, et al. JACC. 2009 Jan 13;53(2):184-92

SENIORS: NevibololStudy of the Effects of Nebivolol Intervention on Outcomes and Hospitalisation in Seniors with Heart Failure)

Ghio S, et al. Eur Heart J. 2006;27: 562–568

SWEDIC: Carvedilol

Bergstrom A. Eur J Heart Fail. 2004;6:453-61.

Swedish Doppler-echocardiographic study

Statins in diastolic HF

Fukuta H. Circulation. 2005;112:357-363

RR death [95% CI] 0.20 [0.06 to 0.62]; P=0.005

Ongoing trials

• Trial of Aldosterone Antagonist Therapy in Adults With Preserved Ejection Fraction Congestive Heart Failure (TOPCAT)

• Start Date: August 2006

• Estimated Completion Date: July 2013

• Spironolactone vs. placebo

• N = 4500

ClinicalTrials.gov: NCT00094302

Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.