DIASTOLIC HEART FAILURE /

Heart Failure with Preserved

Ejection Fraction (HFpEF)
Andreas Arie Setiawan
Fk Universitas Diponegoro

PIT PAPDI SEMARANG 22-24 JULI 2016

cardiac anatomy and physiology

www.wallpaperstone.com
PULMONARY VENOUS PRESSURE

Input

Filling Emptying
ED volume x Stroke
= volume
EFeffective
LV Distensibility Contractility x
Relaxation Afterload
Left atrium Preload Heart
Mitral valve Structure rate
Pericardium
Diastolic function Systolic function

Output

CARDIAC OUTPUT
Block diagram of left ventricular pump performance
(Little, 2001)
 Definition

Heart failure (HF):

A clinical syndrome of inadequate oxygen
delivery to metabolizing tissues resulting from
any cardiac structural or functional impairment
of ventricular filling or ejection of blood

Eur Heart J 2012;33:1787-1847.

Circulation 2013;128:e240-327.
 Types of Heart failure
Classification Ejection
Fraction (EF)
Heart failure with reduced ejection < 40%
fraction (HFrEF)
Formerly referred to as systolic
heart failure
Heart failure with preserved > 50%
ejection fraction (HFpEF)
Formerly referred to as diastolic
heart failure
HFpEF borderline 41-49%
HFpEF improved (patients with a
Circulation 2013;128:e240-327. > 40%
history of HFrEF)
 Clinical presentation
Sign/Symptom HFpEF HFrEF

Dyspnea on 60% 73%

exertion
Nocturnal 55% 50%
dyspnea
Lower extremity 35% 46%
edema
Rales 72% 70%

Circulation 2002;105:1387-93.
J Am Coll Cardiol 2007;50:768-77.
Ann Med 2013;45:37-50.
 Heart failure severity
NYHA Functional
Classification ACCF/AHA HF Staging
Clas Description Stag Description
s e
I No limitation of physical activity. A At high risk for HF but without structural
Ordinary physical activity does not heart disease or symptoms of HF
cause HF symptoms
II Slight limitation of physical activity. B Structural heart disease but without signs
Comfortable at rest, but ordinary or
physical activity results in symptoms of symptoms of HF
HF
III Marked limitation of physical activity. C Structural heart disease with prior or
Comfortable at rest, but less than current
ordinary activity causes symptoms of symptoms of HF
HF
IV Unable to carry on any physical activity D Refractory HF requiring specialized
without symptoms of HF, or symptoms
Circulation 2013;128:e240-327. interventions
of HF at rest
Risk factors for HF

HFpEF HFrEF
Age Coronary artery disease
Gender (females) Family history of heart disease
Hypertension Hypertension
Diabetes Diabetes
Obesity Obesity

J Card Fail 2010;16:475-539.

Ann Med 2013;45:37-50.
HF pathophysiology
Normal HFrEF HFpEF

www.biomerieux-diagnostics.com
 HFpEF pathophysiology

Ventricular hypertrophy

Inflammation Neurohormones
LV

Impaired cardiac relaxation

Ann Med 2013;45:37-50.
Cardiol Res Pract 2013;824135.
PULMONARY VENOUS PRESSURE

Input

Filling Emptying
ED volume x Stroke
= volume
EFeffective
LV Distensibility Contractility x
Relaxation Afterload
Left atrium Preload Heart
Mitral valve Structure rate
Pericardium
Diastolic function Systolic function

Output

CARDIAC OUTPUT
Block diagram of left ventricular pump performance
(Little, 2001)
Treatment for HFpEF
 HFpEF Treatment options

Non-pharmacologic Pharmacologic
Diuretics
Sodium and fluid
ACE inhibitors/ARBs
restriction
Regular exercise Aldosterone
Weight loss antagonists
-blockers
Calcium channel
blockers
Digoxin
Statins
 Diuretics in HFpEF

No mortality benefit of diuretics

Loop diuretics useful in relieving HF symptoms
Thiazide diuretics may reduce the risk of HFpEF
Heart failure guidelines
Management of volume overload symptoms
Therapeutic option for control of hypertension

Eur Heart J 2012;33:1787-1847.

Circulation 2013;128:e240-327.
 ACE inhibitors/ARBs in HFpEF
Improve symptoms but no mortality benefit in HFpEF from
prospective trials (PEP-CHF, CHARM-PRESERVE, I-PRESERVE)
Utility in HFpEF driven by co-morbidities (diabetes, CAD,
CKD)
Heart failure guidelines
First line medication for hypertension management in
HFpEF
ARBs may be considered to decrease hospitalization
Use if compelling co-morbidities
Manage co-morbidities in HFpEF (diabetes, CAD, CKD)
Eur Heart J 2012;33:1787-1847.
Circulation 2013;128:e240-327.
 Aldosterone antagonists in HFpEF

No mortality benefit in HFpEF

Reductions in HF symptoms and hospitalizations
Heart failure guidelines
No specific recommendations on the use of
aldosterone antagonists, but could be adjunctive
treatment for hypertension management

Eur Heart J 2012;33:1787-1847.

Circulation 2013;128:e240-327.
Chronotropic medications

-blockers
Calcium channel blockers
Digoxin
 -Blockers
Proposed benefits in HFpEF
Decrease chronotropy
Decrease myocardial oxygen demand
Increase left ventricular filling time
Efficacy data in HFpEF
Small trials have demonstrated improvement of HF
symptoms and left ventricular function with one
study demonstrating mortality benefit

Am J Cardiol 1997;80(2):207-9.
Eur J Heart Fail 2004;6:453-61.
J Am Coll Cardiol 2009;53:2150-8.
 -Blockers in HFpEF

Mortality benefit?
Useful for patients with atrial fibrillation or a history
of coronary artery disease
Heart failure guidelines
First line medication for hypertension
management in HFpEF
Management of atrial fibrillation

Eur Heart J 2012;33:1787-1847.

Circulation 2013;128:e240-327.
 Calcium channel blockers
Non-DHPs: diltiazem, verapamil
Proposed benefits in HFpEF
Decrease chronotropy
Decrease inotropy
Efficacy data in HFpEF
Two studies showed enhanced ventricular
relaxation and filling

Am J Cardiol 1990;66:981-86.
Int J Clin Pract 2002;56;57-62.
 Calcium channel blockers in HFpEF

Lack of large randomized controlled trials assessing

morbidity and mortality in HFpEF
Useful for rate control in patients with atrial
fibrillation
Heart failure guidelines
No specific recommendations on the use of
calcium channel blockers, but could be adjunctive
treatment for hypertension or atrial fibrillation

Eur Heart J 2012;33:1787-1847.

Circulation 2013;128:e240-327.
 Digoxin
Proposed benefits in HFpEF
Decrease chronotropy
Efficacy data in HFpEF
Conflicting results from post-hoc analyses of DIG
study
Heart failure guidelines
No specific recommendations for digoxin in HFpEF,
but could be used in patients atrial fibrillation
Eur Heart J 2006;27(2):178-86.
Am J Cardiol 2008;102:1681-6.
Eur Heart J 2012;33:1787-1847.
Circulation 2013;128:e240-327.
 HFpEF Targets

-blocker HFpEF
Non-DHP CCB
Digoxin Activation of Cardiac
sympathetic Renin
NS output

Vasoconstricti
Heart rate Angiotensin I
on
ACEI
Cardiac Angiotensin II ARB
filling time
Cardiac
remodeling
Cardiac Aldosterone
filling pressure Na/H2O
retention
Aldosterone antagonist
Diuretic
Adapted from Goodman & Gilman's The Pharmacological Basis of Therapeutics 2011.
 Investigational therapies in HFpEF

Sildena
fil

Ranolazi
ne

Alegabriu
m
Pharmacotherapy 2011;31(3):312-31.
JAMA 2013;309(12):1268-77.
Mortality benefit

HFpEF HFrEF
Aldosterone antagonists

?
ACE inhibitors
ARBs
-blockers

Vasodilators
 treatment recommendations

With limited prospective efficacy data, lack of

consensus treatment recommendations for
patients with HFpEF
Guidelines vague on first line
recommendations
HFpEF treatment selection is driven by
management of symptoms and co-morbid
disease states

Circulation 2013;128:e240-327.
Eur Heart J 2012;33:1787-1847
 Treatment of HFpEF
HFpEF Treatment Recommendations
Characteristic
Volume overload Diuretic
symptoms
Hypertension ACE inhibitor, ARB, -blocker

Atrial fibrillation -blocker, non-DHP CCB, digoxin,

amiodarone
Diabetes/CKD ACE inhibitor, ARB

Coronary artery ACE inhibitor or ARB + -blocker

disease
Circulation 2013;128:e240-327.
Eur Heart J 2012;33:1787-1847
 Summary

Pathophysiology, etiology, and treatment for HFpEF are

distinct
Lack of mortality benefit for medications treating HFpEF
Future studies are necessary to determine optimal
therapies
Due to lack of strong clinical evidence, treatment guidelines
recommend empiric medication selection based on
symptoms and co-morbidities
Thank you