heart failure with preserved ejection fraction

1. Heart Failure With
Preserved Ejection Fraction
(HFpEF)
Dr. Izaz Ali Khan
PGR Cardiology
MTI-KTH,Peshawar

2. Heart Failure
• DEFINITION:
Heart failure is a complex clinical syndrome
characterized by impaired myocardial performance
and progressive maladaptive neuro-hormonal
activation of the cardiovascular and renal system
leading to circulatory insufficiency and congestion.

3. • Heart Failure is diagnosed clinically not by
echocardiography
It is a combination of
Congestive Findings:
Orthopnea and paroxysmal nocturnal dyspnea (PND)
Exertional Dyspnea, Crackles/Pulmonary Edema/Pleural
Effusions, Increased JVP>8cmH20,
Peripheral edema/ascites, S3 in patients>40yrs.
Low-output Findings:
Severe fatigue, Narrow Pulse pressure, Cold and clammy
extremities, compensatory tachycardia. Renal failure and
hyponatremia and impaired mentation, drowsiness, central
hypoventalation at advanced stage

5. Types of Heart Failure
• After HF is defined clinically, echocardiography is used to
differentiate the three major types.
1. HF secondary to LV systolic dysfunction where EF is
<40% (HFrEF)
2. HF secondary to LV diastolic dysfunction where EF
is >50% (HFpEF) (HF e EF 40-50% is a form of systolic
dysfunction with predominant diastolic failure generally considered
HFpEF or called HFmrEF)
3. HF due to severe valvular disease in which the ventricular
function is initially normal
Two additional types of HF are High output HF and
Predominant or Isolated Right Heart Failure

6. CLASSIFICATION
• The ACC/AHA classify HF on the basis of evolution of the disease
1. Stage A: Patient at high risk of developing HF without structural
heart disease or symptomatic HF
2. Stage B: Patient with structural heart disease who have not yet
developed symptoms of HF
3. Stage C: Patient with structural heart disease with prior or current
symptoms of HF
4. Stage D: patient with refractory end stage HF who require
specialized advanced treatment

8. The Killips classification grades the severity of acute
decompensated HF

9. Heart Failure with Preserved
Ejection fraction (HFpEF)
• The ACC/AHA guidelines for the management of HF
defines HFpEF as
the clinical syndrome that includes
1. Signs and symptoms of congestive heart failure
2. Left ventricular ejection fraction >50%
3. Evidence of diastolic dysfunction as determined by
Doppler echocardiography, cardiac catheterization and
natriuretic peptide measurement.

11. • In order to make a diagnosis of HFpEF, two
other diagnosis have to be ruled out:
1. Transient, ischemic LV systolic dysfunction.
2. Dynamic ischemic MR in patients with off/on or
persistent inferior wall dysfunction.

12. Pathophysiology
• Most pathophysiological abnormalities in patient with HFpEF
are related to Diastolic dysfunctions
There are two major determinants of diastolic function
LV Relaxation: (LV doesn’t relax well)
it relates to ATP based cellular mechanism involved with actin
myosin cross bridge detachment. Thus, ischemia which
decrease intracellular ATP availability would prolong the time for
relaxation.
LV stiffness: LV is not elastic enough to further distend after
relaxation and accept the diastolic filling . This limited LV filling
results in backward rise of PCWP despite normal functions.

13. • OTHER MECHANISMS:
• Impaired contractility: normal EF doesn’t necessarily
imply normal contractility. EF, being equal to stroke volume
divide by end diastolic volume, EF is affected by
contractility but also by changes in loading conditions
• Increased arterial stiffness which leads to exaggerated
exertional hypertension
• Pulmonary vascular stiffness with rise in PA pressure
disproportionate to LA pressure
• Very small and stiff LV cavity
• Volume overload conditions

14. Causes of HFpEF
• Hypertension with or without LV hypertrophy.
Hypertension leads to diastolic dysfunction and is the most common risk factor of
diastolic HF. LV hypertrophy is common in diastolic HF.
Other risk factors for diastolic dysfunction is Age, Female sex , diabetes, obesity,
renal failure and AF.
• Coronary artery disease:
CAD is less common etiology of HFpEF than HFrEF. But it still considered
the underlying etiology in 25 to 45% cases
it may contribute to diastolic dysfunction. Infact in patient with CAD the
rise in LVEDP is an early hemodynamic manifestation of angina induced by pacing
or exercise
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy
• Constrictive Cardiomyopathy

15. Clinical Presentation
A. Demographics
When compared with patients of HFrEF, those with HFpEF tend to be
older, more likely to be female with associated comorbidities of
Hypertension, diabetes, obesity and chronic kidney disease.
B. Symptoms
The diagnosis of HFpEF is limited to patient with current or prior
symptoms of HF (Stage C and D AHA/ACC).
The symptoms are indistinguishable from those e HFrEF. Some
Patients presents with only exertional fatigue or dyspnea, other
experience overt symptoms of left sided (dyspnea, orthopnea, PND)
and Right sided (edema, abdominal bloating) heart failure.

16. • Signs:
Similar to HFrEF. Patients should be evaluated
for typical signs of right sided ( elevated JVP,
hepatic congestion, ascites and lower extremities
edema) and left sided (pulmonary edema and
pleural effusion) congestion

18. Diagnostic Tests

19. Specific Diagnostic testing
• ECHOCARDIOGRAPHY
It is the primary imaging modality for evaluating a
patient with clinical syndrome of CHF and a modality of
choice evaluating LV diastolic function. The most commonly
used parameter in clinical practice is the Doppler
interrogation of transmitral flow pattern and tissue Doppler
evaluation of annular velocity to determine the E/e` ratio.

20. • Transmitral flow pattern.
In sinus rhythm using pulsed wave Doppler across
the mitral inflow tract generates two waves : the early E
wave, corresponding to rapid ventricular filling as the mitral
valve opens and the A wave which reflects atrial contraction.
E wave deceleration time is time from peak E inflow velocity
to decay to zero.
With age, hypertension or ischemia the viscoelastic
properties of ventricles decreases. The atrial kick is
proportionately greater and E/A reversal may occur.
However multiple other factors can affect E/A ration and
recent guidelines has abandoned this as a sensitive
measure of diastolic dysfunction

21. • Tissue Doppler imaging of the mitral annular velocity.
In the evaluation of diastolic function, TDI is used to
measure the velocity of movement of the septal and lateral aspect
of the mitral annulus.
The myocardial velocities have three components: systolic
wave (S`), early diastolic wave (e`) and late diastolic wave (a`),
In the earliest stage of Diastolic dysfunction the velocities
of annular motion decrease. Septal e`<8cm/s and/or lateral
<10cm/s suggests the presence of diastolic dysfunction
Unlike the tranmitral flow pattern there is no pseudo
normalization pattern and with annular velocity making it easier to
differentiate normal from abnormal diastolic function

22. • E/e` ratio
the ratio of E velocity (obtained from transmitral flow
pattern) and e` (obtained from TDI) can be used to estimate
the filling pressure.
the E/e` ratio >15 roughly correlated with PCWP
>12mmhg suggest diastolic dysfunction
In patients with predominantly exertional symptoms it
is useful to perform exercise echocardiography to evaluate for
the presence of diastolic dysfunction.

23. • Invasive hemodynamic assessment
not routinely performed but is indicated when non
invasive studies cannot adequately asses filling pressure
MRI: it can useful to measure ventricular function, mass and
volumes when echocardiography is not diagnostic.
Endomyocardial biopsy: used in selected circumstances
particularly when there is a high suspicion of a disorder
whose diagnostic will profoundly impact management and
prognosis. Most common indication is restrictive
cardiomyopathy.
Elevated NT-pro BNP and BNP:
NT-pro bnp >220pg/ml or BNP > 200pg/nl suggest
diastolic dysfuntion unless caused by another mechanism.

26. Management

28. Treatment of HFPEF
• Unlike systolic HF no drug has been shown to improve
survival in HFpEF per se and thus no drug is specifically
indicated to improved survival in HFpEF. The only
treatment that improves outcomes is the aggressive
treatment of the underlying disease.
• Hypertension and Congestion management remain the
mainstay treatment.
• Based on the result of CHARM-P and TOPCAT trails,
Candesartan and Spironolactone respectively have been
shown to reduce hospitalization in HFpEF

29. Contd…
• In trail (EMPEROR-preserved) of patients with an
LVEF>40, NYHA class 2 to 4 HF symptoms and elevated
NT-pro BNP had a lower risk of had a lower risk of HF
hospitalization but similar cardiovascular death to
placebo. Increased incidence of UTI was reported

32. THERAPY (mortality benefits)
A. Salt restriction is a reasonable dietary recommendation
in patient e symptomatic HFpEF in order to reduce
congestion
B. Diuretics should be used for symptomatic treatment of
edema and congestion. Chronic use of loop diuretics may
lead to diuretics congestion. In this scenario a thiazide or
potassium sparing diuretics may be used to augment
diuresis.
C. Angiotensin receptor blockers. CHARM-P AND I-
PRESERVE trails evaluated the use of ARBs in HFpEF.
The trail showed no difference in the primary end point of
mortality and Hospitalization

33. D. ACE inhibitors. PEP-CHF trial randomized patient e
LVEF>40 to perindopril versus placebo.no all cause mortality
benefit was met.
E. Beta blocker. SENIORS trail randomized patient e LVEF
>35 to nebivolol verses placebo e 35 % primary end point
mortality benefits and HF mortality in nebivolol group. J-DHF
randomized HF patient e LVEF>40 to carvedilol and placebo.
No difference in CV death and Unplanned hospitalization
between two groups.
F. Digoxin. DIG trail evaluated the use of digoxin in patients e
HF having EF>45%. No significant difference in mortality.
There was non-significant trend toward decreased HF
hosptlization.

34. G. Spironolactone. The TOPCAT trail randomized HF
patients with EF >45, showed that it reduced hospitalization
but no effect on CV death. ALDO-HF trail randomized HF
patients e EF>50% to spironolactone and placebo found no
significant difference in the endpoints of changes in diastolic
function by echo (E/e`) and maximal exercise capacity.
H. Nitrates. NEAT trail randomized HFpEF patients to
isosorbide mononitrate or placebo with subsequent cross
over to the other group . The trail revealed no significant
change in daily activity level, 6 mins walk disease and quality
of life scores.
I. Sildenafil. RELAX trail randomized HFpEF pts to sildanafil
for 24weeks found no significant improvement in VO2 max on
CPET.

35. • TREATMENT (SUMMARY)
To date no class of medications have shown mortality
benefit for the patients with HFpEF.
Hypertension contributes to HFPEF pathophysiology in most
patients, should be treated according to established
guidelines. It is reasonable to use betablockes, ACE
inhibitors, ARBs and MRA for this purpose. Candesartan and
spironolactone have shown reduced HF hospitalization in
trails.
Loop diuretics should be used for symptomatic benefit. Can
be combined with thiazide diuretics to treat diuretic
resistance.
Revascularization should be reserved for the patients in
whom ischemia is thought to play a major adverse role in
cardiac function

36. PROGNOSIS
• Recent meta-analysis has shown that the yearly
mortality of HFpEF is lower than the mortality of systolic
HF (30% lower). Overall, however the mortality of
HFpEF is high and this is partly explained by the old age
and the non cardiac comorbidities of HFpEF.
Furthermore no specific therapy improves survival in
HFpEF.
• In HFpEF, the mode of death is cardiovascular in 60%,
only 15% due to HF, 27% are sudden deaths and 5% MI
• Both types of HF (HFrEF & HFpEF) are associated with
same yearly risk of re-hospitalization for HF.

38. Follow up
• This is relatively understudied. Patients with HF,even if
symptoms are well controlled,require follow-up to ensure
continued optimization of therapy,to detect asymptomatic
progression of HF or its comorbidities and to discuss any new
advances in care.
• Guidelines recommend follow up at intervals no longer than 6
months.
• Ecg should be done annually to detect QRS prolongation.
• Serial Echocardiography is generally not necessary,although
should be repeated if there is deterioration in clinical status..
• Monitoring with biomarkers(particularly BNP and Pro BNP)
• Telemonitoring

40. •THANKS