The document discusses evidence-based management of heart failure with preserved ejection fraction (HFpEF), detailing diagnostic criteria, pathophysiology, and epidemiology. It highlights the complexity of HFpEF, including comorbid conditions and non-diastolic mechanisms, and emphasizes the importance of proper diagnosis and treatment approaches. Ongoing clinical trials and various treatment strategies, including the use of traditional heart failure medications, are also mentioned.

1. 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

2. 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

3. 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

4. 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.

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

6. Pathophysiology
Cliger C, et al. AJGC. 2006;15:50–57

7. Aurigemma GP, et al. Circulation 2006; 113: 296–304
Systolic HF
Normal heart
Diastolic HF
Pathophysiology

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

9. 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.

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

11. 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.

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

13. 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 systolic
Ventricular
Vascular
Renal
Neurohumoral
Non-CV
Normal EF Heart Failure
Bench T, et al. Current Heart Failure Reports 2009, 6:57–64

14. 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

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

16. Hypertension and heart failure in
the setting of normal EF
Cliger C, et al. AJGC. 2006;15:50–57

17. Prolonged QRS and mortality
Hummel SL, et al. J Cardiac Fail 2009;15:553-60.
N=872

18. Prolonged QRS and mortality
Hummel SL, et al. J Cardiac Fail 2009;15:553-60.
N=872

19. 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.

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

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

22. Echocardiography
Sm = peak systolic
velocity
septal side of the mitral valve annulus or base.
Em = peak early
diastolic velocity
Am = peak atrial
contraction velocity
Sanderson JE. Prog Cardiov Dis. 2006;49(3): 196-206

23. 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

24. 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, 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.

25. 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.)

26. Cardiac MRI vs. Echocardiography
Rademakers FE. Prog Cardiov Dis. 2006;49(3): 215-27.

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.

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

29. 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.

30. Completed trials for HF with preserved EF
Lam CSP. Ann Acad Med. 2009;38(8): 663-666.

31. Hong Kong trial
• ACE vs. ARB vs. diuretics
Yip GWK, et al. Heart 2008;94;573-580.

32. VALIDD Trial: supporting antihypertensive Tx
Valsartan In Diastolic Dysfunction
Lowering blood pressure
improves diastolic function
irrespective of the type of
antihypertensive
agent used.
Solomon SD. Lancet 2007; 369: 2079–87

33. 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

34. OPTIMIZE – HF: Betablockers
Hernandez, et al. JACC. 2009 Jan 13;53(2):184-92

35. SENIORS: Nevibolol
Study 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

36. SWEDIC: Carvedilol
Bergstrom A. Eur J Heart Fail. 2004;6:453-61.
Swedish Doppler-echocardiographic study

37. 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

38. 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

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