Heart Failure with Normal Ejection Fraction (HFNEF): What the hospitalist needs to know

Moises Auron, MD FAAP FACP Hospital Medicine

01/26/10

Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Diagnostic Criteria
• Symptoms and signs compatible with heart failure • Left ventricular ejection fraction >50% • Exclusion of severe valvular disease and pericardial disease • Diastolic dysfunction
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
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Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Epidemiology
• 20% to 60% of patients with HF • Increasing prevalence

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Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479. Owan T, et al. NEJM. 2006;355:251-9

Epidemiology
Increased prevalence with age: Age Prevalence 50 15% 50-70 33% > 70 50%

Zile MR. Circulation. 2002; 105(11): 1387-93.
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Epidemiology
• More frequent in elderly female
– Diastolic HF – 79% – Systolic HF – 49%

• Asymptomatic – more frequent presentation • ADHERE
– Elderly – HTN – ↓ ACEI/ARB
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- Female - ↓ previous MI - ↓ in-hospital mortality
Masoudi FA. JACC. 2003; 41(2): 217-23. Yancy CW, JACC. 2006; 47(1):76-84

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

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

Aging and HF with preserved EF
• Elderly patients associated disorders – CAD – DM – Aortic stenosis – Atrial fibrillation – Obesity – Sex-specific  women

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

Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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

Structural abnormalities
• Chamber remodeling
– Normal EDV – ↑ wall thickening – ↑ ratio myocardial mass/cavity volume – ↑ ratio wall thickness/chamber radius

• ↑ Cardiomyocyte diameter • ↑ Collagen and extracellular matrix
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Aurigemma GP, et al. Circulation 2006; 113: 296–304

Structural abnormalities
Systolic HF

Normal heart

Diastolic HF

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

Myocardial disorders associated with HF and normal LVEF
• • • • Restrictive cardiomyopathy Obstructive hypertrophic cardiomyopathy Nonobstructive hypertrophic cardiomyopathy Infiltrative cardiomyopathies

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

Restrictive Cardiomyopathy

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NEJM. 1997;336(4):267-76.

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

Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Physiologic mechanisms
• Lusitropism – dependent on Ca2+ efflux • Dependent on ATP – impaired in ischemia – ACEI improves diastolic dysfunction in HCM • Na2+ gradient (outward  inward) promotes Ca2+ efflux • Digitalis impairs Na2+ /K+ ATPase • Β-agonists
– Inotropic: Ca2+ influx – Lusitropic: Ca2+ re-uptake

• Titin – recoil/ Ca2+ de-sensitizer

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Zile MR. Circulation. 2002; 105(12):1503-8. Gerull B. Nat Genet. 2002; 30(2):201-4

Physiologic mechanisms
• Diastole – determined by:
– Myocardial relaxation
• • • • Prior to Aortic valve closure Isovolumetric relaxation “Untwisting” of LV  Suction with LA/LV P gradient Promotes rapid early diastolic filling

– LV elasticity and distensibility
• In late diastole  relaxed myocytes • LV: compliant and distensible  minimal resistance

– Atrial contraction - 20-30% of LV filling volume
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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
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Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Pathophysiology

Aurigemma GP. NEJM. 2004;351:1097-105.
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Cliger C, et al. AJGC. 2006;15:50–57

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Little WC. Heart Failure Reviews. 2000;5:301-6. Kitzman DW. JACC. 1991;17(5):1065-72,

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Chattopadhyay S. Circ Heart Fail. 2010;3:35-43.

Pathophysiology

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Ting Tan Y, et al. JACC. 2009;54(1):36–46

Single syndrome hypothesis

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

Diastolic CHF?
Myocardial systolic Ventricular Vascular

Renal

Normal EF Heart Failure Non-CV Neurohumoral

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

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

Volume overload

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

Prolonged QRS and mortality
N=872

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

Prolonged QRS and mortality
N=872

Hummel SL, et al. J Cardiac Fail 2009;15:553-60.
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Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Clinical manifestations
• Most frequent: Asymptomatic • Less severe presentation
– Decreased exercise capacity
• Increased LA/PVP • Poor tolerance to tachycardia and Afib • HTN/LV stress  Flash pulmonary edema

– Neurohumoral activation – Decreased Quality of Life
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Clinical manifestations
• Restrictive CM
– Increased JVP – Kussmaul’s sign – S3
• Abrupt cessation of rapid ventricular filling

– Functional MR/TR

http://www.radrounds.com/photo/cardiac-amyloidosis-cardiac-2

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Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Diagnosis
• ↓ Slow rate of ventricular relaxation • ↑ LV filling pressure in a patient with normal LV volumes and contractility.
– LVEF > 50% – LVEDP < 97 ml/m2

• Clinical diagnosis - HF in a patient who is shown to have a normal LVEF and no valvulopathy • Doppler echocardiography (TTE) • BNP levels in addition to TTE improve diagnostic accuracy.
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Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

Echocardiography

E = early filling A = atrial contraction
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Aurigemma GP. NEJM. 2004;351:1097-105.

E = early filling
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e’ = Early tissue doppled lengthening velocity Bursi F, et al. JAMA 2006;296:2209-2216.

Pulmonary vein flow

S – systolic flow – LA relaxation D – diastolic flow – forward flow from Pulmonary veins into LA AR – atrial systole – retrograde flow into Pulmonary veins
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Redfield MM. JAMA. 2003;289(2):194-202.

Echocardiography
Sm = peak systolic velocity

Em = peak early diastolic velocity Am = peak atrial contraction velocity

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septal side of the mitral valve annulus or base.
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 and midwall fractional shortening .
– 30-50% cases – Motion of basal LV

• Ejection is relatively preserved because of increased radial function.
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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.

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Circumferential strain at the LV apical level in a patient with a LAD-related MI. Reduced systolic shortening (strain) in the anterior, septal, and inferior 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.)

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Cardiac MRI vs. Echocardiography

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

Diagnosis: BNP
• Levels > 62 pg/ml
– 85% sensitivity – 83% specificity

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Lubien E. Circulation. 2002;105(5):595-601

Diagnosis: ESC algorithm

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Maeder M. State of the Art: HFNEF. JACC. 2009:53(11): 905-18

Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Prognosis
N = 6076; 47% EF > 50% N = 2802; 31% EF > 50%

HR 1.13; (95%CI 0.94-1.36; P= 0.18) Adjusted HR for death 0.96; P = 0.01

Owan TE. NEJM. 2006;355:251-9. Bhatia RS. NEJM. 2006;355:260-9.
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Prognosis
N= 24,501

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

Outline
• • • • • • • • Diagnostic Criteria Epidemiology Etiology Physiology and Patophysiology Clinical Manifestations Diagnosis Prognosis Treatment

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Treatment
• Limited evidence. • Similar drugs as for systolic CHF justified by co-morbid conditions:
– Atrial fibrillation, HTN, DM, CAD

• Treatment is based on the control of physiological factors (BP, HR, blood volume, and myocardial ischemia)

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

Completed trials for HF with preserved EF

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

Hong Kong trial
• ACE vs. ARB vs. diuretics

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

VALIDD Trial: supporting antihypertensive Tx
Valsartan In Diastolic Dysfunction

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

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Solomon SD. Lancet 2007; 369: 2079–87

SWEDIC: Carvedilol
Swedish Doppler-echocardiographic study N = 113

No change in: •Deceleration time •Isovolumic relaxation time •Pulmonary vein flow velocity

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

SENIORS: Nevibolol
Study of the Effects of Nebivolol Intervention on Outcomes and Hospitalization in Seniors with Heart Failure) Age > 70 y/o.
N = 1359 N = 752

van Veldhuisen DJ, et al. JACC. 2009;53(23):2150–8
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OPTIMIZE – HF: Betablockers
Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure N = 7154 elderly

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

OPTIMIZE – HF: Betablockers

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

Calcium channel blockers
• Verapamil – Lusitropic effect – Negative chronotropic – Anti-ischemic – Small studies • Increased peak LV diastolic filling in HCM

Bonow, RO. Circulation. 1985; 72(4):853-64.
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Hypertension treatment and LVH

11% 8%

10%

13%

6%

80 trials N = 3767 (treatment) N = 346 (placebo)
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Klingbeil AU. Am J Med. 2003;115:41– 46.

Statins in diastolic HF

RR death [95% CI] 0.20 [0.06 to 0.62]; P=0.005
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Fukuta H. Circulation. 2005;112:357-363

Ongoing trials: Spironolactone
• 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
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ClinicalTrials.gov: NCT00094302

New ventures: Isosorbide/Hydralazine

• Improved HTN, diastolic function and exercise capacity. • Decreased soluble V-CAM1 levels. • No reductions in LVH, cardiac fibrosis, or pulmonary congestion.
Wilson RM. Hypertension. 2009;54:583-590.
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Hunt, et al. 2009 ACCF/AHA Heart Failure Guidelines. (Circulation. 2009;119:e391-e479.

HFNEF: What the hospitalist need to know
• Recognize HFNEF as a cause for AHF
– Elevated filling pressures – Exercise intolerance / Flash pulmonary edema

• Recognize HFNEF subtypes • Distinguish the etiologies of restrictive CM • Optimize treatment of:
– HTN, ischemia, volume overload – HCM
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