HFPEF

1. Heart Failure with
Preserved Ejection Fraction
Birju Patel, MD MPH

2. Key points
• Relatively recent term, HFPEF = clinical dx of CHF +
preserved EF
• Half of all CHF, just as lethal
• Characterized by abnormal stiffness (up+left shift of
LV end diastolic pressure-volume relationship –
EDPVR)
• Especially fragile exercise capacity, fatigue, DOE
• Unclear how it happens, comorbidities likely key
• No tx strategy for HFREF has worked in HFPEF

3. Terminology
Energy
CAD
Structure /
function
Cardiomyopathy
Usually reserved for genetic
pathologies, excluding ischemic,
valvular, hypertensive etiologies
Dilated (eccentric), hypertrophic
(concentric), or restrictive
Congestive heart
failure
syndrome
HFREF
Systolic +/- diastolic
dysfunction
HFPEF
Diastolic but no systolic
dysfunction
Electrical
Arrhythmia
 ~2005
 ICD 9 – 1975
ICD 10 – 1990
pathology
clinical
physiology
clinical

4. Terminology
Energy
CAD
Structure /
function
Cardiomyopathy
Usually reserved for genetic
pathologies, excluding ischemic,
valvular, hypertensive etiologies
Dilated (eccentric), hypertrophic
(concentric), or restrictive
Congestive heart
failure
syndrome
HFREF
Systolic +/- diastolic
dysfunction
HFPEF
Diastolic but no systolic
dysfunction
Electrical
Arrhythmia
 ~2005
 ICD 9 – 1975
ICD 10 – 1990
pathology
clinical
physiology
clinical
Key point 1A
The term HFPEF is
relatively new

5. Working definition
• Clinical diagnosis of congestive heart failure
Framingham criteria – 2 major or 1 major + 2 minor
• Ejection fraction normal (>50%)
• No consensus here in US on need for DD or hypertrophy
Major Minor
PND or orthopnea DOE
Rales Nocturnal cough
HJR Tachycardia
S3 Ankle edema
JVD (or elevated CVP) Hepatomegaly
CXR pulmonary edema CXR engorged pulm vessels
Cardiomegaly Pleural effusion
10lb weight loss with diuretics Decreased vital capacity
HPI
PE
Imaging
Empiric!

6. HPI
Working definition
• Clinical diagnosis of congestive heart failure
Framingham criteria – 2 major or 1 major + 2 minor
• Ejection fraction normal (>50%)
• No consensus here in US on need for DD or hypertrophy
Major Minor
PND or orthopnea DOE
Rales Nocturnal cough
HJR Tachycardia
S3 Ankle edema
JVD (or elevated CVP) Hepatomegaly
CXR pulmonary edema CXR engorged pulm vessels
Cardiomegaly Pleural effusion
10lb weight loss with diuretics Decreased vital capacity
PE
Imaging
Empiric!
Key point 1B
HFPEF = CHF + EF>50

7. Epidemiology
Prevalence, hospitalizations, mortality

8. Increasing proportion of HFPEF
Owan TE et al. N Engl J Med 2006;355:251-259.

9. Increasing proportion of HFPEF
Key point 2A
Half of all CHF is HFPEF
Owan TE et al. N Engl J Med 2006;355:251-259.

10. Admissions for HFPEF vs HFREF
¼ of CHF discharges
are readmitted
within 30d
Mortality is high
post-discharge
Owan TE et al. N Engl J Med 2006;355:251-259.

11. Significant mortality in HFPEF
Mean age 74, significant comorbidities including CAD, DM, HTN
Owan TE et al. N Engl J Med 2006;355:251-259.

12. Significant mortality in HFPEF
Key point 2B
Significant mortality!
Owan TE et al. N Engl J Med 2006;355:251-259.
Mean age 74, significant comorbidities including CAD, DM, HTN

13. Pathophysiology and
management

14. Physiologic definition
• Elevated LVEDP (filling pressure)
• Especially during exacerbation or exertion
• Increased stiffness (LV EDPVR)
Systolic dysfunction
Impaired contractility
Diastolic dysfunction
Impaired relaxation
Higher LVEDP
Burkhoff. Heart Failure With a Normal Ejection Fraction: Is It Really a Disorder of Diastolic Function? Circulation. 2003; 107:656-658

15. Physiologic definition
• Elevated LVEDP (filling pressure)
• Especially during exacerbation or exertion
• Increased stiffness (LV EDPVR)
Systolic dysfunction
Impaired contractility
Burkhoff. Heart Failure With a Normal Ejection Fraction: Is It Really a Disorder of Diastolic Function? Circulation. 2003; 107:656-658
Key point 3
Abnormal stiffness =
up+left shift LV EDPVR

16. TTE grades of diastolic dysfunction
E – Transmitral doppler of Early passive filling
A – Transmitral doppler of Atrial contraction
e’ – Tissue Doppler of early MV ring
=
Though paradoxically flips with severe DD
E/A
When extreme (>15), may correlate with LVEDP
=E/e’
Normal G1DD G2DD G3/4DD
Nagueh. Recommendations for the Evaluation of Left Ventricular Diastolic Function by Echocardiography. J Echocardiography. 2008.

17. Poor exercise tolerance – fatigue
and DOE
• Why does exercise make anyone tired?
• VO2max ~ CO x O2 extraction
• Ventilation/lactate threshold
• Normally CO increases with HR, SV, contractility while
simultaneously decreasing stiffness to improve filling
to match needs
• In HFPEF, HR limits diastolic filling time, stiffness
(EDPVR) paradoxically worsens
Larger LVEDP
necessary,
causes DOE
Limited HR and limited LVEDV
results in non-optimal use of
Frank-Starling curve, reduces
CO (and thus VO2max) and
causes fatigue
Abudiab. Cardiac Output Response to Exercise in Relation to Metabolic Demand in heart Failure with Preserved Ejection Fraction. Eur J Heart Fail. 2013; (15):776-785

18. Poor exercise tolerance – fatigue
and DOE
• Why does exercise make anyone tired?
• VO2max ~ CO x O2 extraction
• Ventilation/lactate threshold
• Normally CO increases with HR, SV, contractility while
simultaneously decreasing stiffness to improve filling
to match needs
• In HFPEF, HR limits diastolic filling time, stiffness
(EDPVR) paradoxically worsens
Larger LVEDP
necessary,
causes DOE
Limited HR and limited LVEDV
results in non-optimal use of
Frank-Starling curve, reduces
CO (and thus VO2max) and
causes fatigue
Abudiab. Cardiac Output Response to Exercise in Relation to Metabolic Demand in heart Failure with Preserved Ejection Fraction. Eur J Heart Fail. 2013; (15):776-785
Key point 4
People with HFPEF
have poor exercise
tolerance

19. Pathogenesis
What mediates stiffening / fibrosis? No theory is
definitive, but many acknowledge high burden of
comorbidities
One way to review is to use an anatomic approach to
disease:
• Cardiac
• Interstitial
• Cardiomyocyte
• Non-cardiac
• Vasculature
• Skeletal muscle

20. Microvascular inflammation
endothelium
cardiomyocyte
interstitial fibrosis
cardiomyocyte stiffening
Paulus. A Novel Paradigm for Heart Failure with Preserved Ejection Fraction. 2013; 62(4)

21. Inside the cardiomyocyte
Kavita Sharma, and David A. Kass Circulation Research. 2014;115:79-96

22. Non-cardiac mechanisms
Kavita Sharma, and David A. Kass Circulation Research. 2014;115:79-96

23. Non-cardiac mechanisms
Key point 5
No definitive
pathogenesis.
Comorbidities likely
key

24. Does treatment modify outcomes?
Beta blocker
ACEi/ARB
Aldosterone Ant
Digoxin
ISDN/hydralazine
Statin
.5 .75 1 1.5
ORFavors tx Favors control
HFREF
OR
.5 .75 1 1.5
Favors tx
HFPEF
Favors control
Copernicus
Comet
Merit-HF
SOLVD
CHARM Added
CHARM Alt
Val-HEFT
EMPHASIS
EPHESUS
RALES
DIG
A-HeFT
CORONA
GISSI-HF
SENIORS
OPTIMIZE
OPTIMIZE
PEP-CHF
I-PRESERVED
CHARM Preserved
OPTIMIZE
TOPCAT
DIG Ancillary
GISSI-HF
Also, phase 3 for neprilysin
inhibitor pending

25. Does treatment modify outcomes?
Beta blocker
ACEi/ARB
Aldosterone Ant
Digoxin
ISDN/hydralazine
Statin
.5 .75 1 1.5
ORFavors tx Favors control
HFREF
OR
.5 .75 1 1.5
Favors tx
HFPEF
Favors control
Copernicus
Comet
Merit-HF
SOLVD
CHARM Added
CHARM Alt
Val-HEFT
EMPHASIS
EPHESUS
RALES
DIG
A-HeFT
CORONA
GISSI-HF
SENIORS
OPTIMIZE
OPTIMIZE
PEP-CHF
I-PRESERVED
CHARM Preserved
OPTIMIZE
TOPCAT
DIG Ancillary
GISSI-HF
Key point 6
No treatment
significantly alters
cardiac events in
HFPEF

26. Key points
• Relatively recent term, HFPEF = clinical dx of CHF +
preserved EF
• Half of all CHF, just as lethal
• Characterized by abnormal stiffness (up+left shift of
LV end diastolic pressure-volume relationship – LV
EDPVR)
• Especially fragile exercise capacity, fatigue, DOE
• Unclear how it happens, comorbidities likely key
• No tx strategy for HFREF has worked in HFPEF