Heart Failure with preserved EF

Heart FailureHeart Failure
withwith
Preserved Ejection Fraction (HFpEF):Preserved Ejection Fraction (HFpEF):
How to diagnose, What to do about it?How to diagnose, What to do about it?
Dr.Vinod SharmaDr.Vinod Sharma
11
National Heart InstituteNational Heart Institute

Heart Failure with PreservedHeart Failure with Preserved
Ejection Fraction (HFpEF)Ejection Fraction (HFpEF)
A leading cause of morbidity & mortality.A leading cause of morbidity & mortality.
Represents 50% of HF cases.Represents 50% of HF cases.
Prevalence of HFpEF relative to HFrEF isPrevalence of HFpEF relative to HFrEF is
increasing at rate of 1% per year.increasing at rate of 1% per year.
22

Similar functional decline, hospitalSimilar functional decline, hospital
readmission rates, economic costs asreadmission rates, economic costs as
HFrEFHFrEF
Key Lesson # 1Key Lesson # 1
HFpEF is not “benign”HFpEF is not “benign”

HFpEF, are as functionally limited as their counterpart with
HFrEF
Survival is poor & similar to HFrEFSurvival is poor & similar to HFrEF
55
Heart Failure with Preserved EjectionHeart Failure with Preserved Ejection
Fraction (HFpEF) -Fraction (HFpEF) - PrognosisPrognosis
Observational study – dismal 5 year survival of only 35 – 40%Observational study – dismal 5 year survival of only 35 – 40%
post hospitalization for HFpost hospitalization for HF
EJM 2006: 355: 251-9EJM 2006: 355: 251-9
““a survival rate similar to advanced, stage 3B, non small cella survival rate similar to advanced, stage 3B, non small cell
lung cancer”lung cancer”
Key reason of high morbidity & mortality of HFpEF is lack ofKey reason of high morbidity & mortality of HFpEF is lack of
evidence based treatment.evidence based treatment.

Key Lesson # 3Key Lesson # 3
99
Know the difference between Diastolic
dysfunction, Diastolic Heart Failure &
HFpEF

Diastolic dysfunction is not unique to DHF.Diastolic dysfunction is not unique to DHF.
Echo evidence of DD is nearly universal inEcho evidence of DD is nearly universal in
HFrEF (systolic HF).HFrEF (systolic HF).
Isolated or pure DHF is rare.Isolated or pure DHF is rare.
Only 2% of patient met criteria for DHFOnly 2% of patient met criteria for DHF
Prasad et al: Circ Heart Fail 2010Prasad et al: Circ Heart Fail 2010
1010

Complementary pathophysiological mechanismComplementary pathophysiological mechanism:-:-
-- Longitudinal LV systolic dysfunction (despite aLongitudinal LV systolic dysfunction (despite a
normal EF)normal EF)
-- Abnormal ventricular – arterial couplingAbnormal ventricular – arterial coupling
-- Abnormal exercise induced vasodilatationAbnormal exercise induced vasodilatation
-- Pulmonary hypertensionPulmonary hypertension
-- Chronotropic IncompetenceChronotropic Incompetence
-- Extracardiac volume overload.Extracardiac volume overload.
1111
HFpEF : Diagnosis & ManagementHFpEF : Diagnosis & Management
What to do?What to do? (contd)(contd)

Diagnosing HFpEF requiresDiagnosing HFpEF requires
diligence & hypervigilancediligence & hypervigilance
1212
Key Lesson # 4

 Symptoms are nonspecific and can be explained bySymptoms are nonspecific and can be explained by
several alternative non-cardiac conditions viz COPD,several alternative non-cardiac conditions viz COPD,
CKD, anemiaCKD, anemia
 Many patients are morbid obese:Many patients are morbid obese:
-- Difficulty estimating JVPDifficulty estimating JVP
-- Estimation of RA pressure by assessment of sizeEstimation of RA pressure by assessment of size
and collapsibility of IVC challengingand collapsibility of IVC challenging
 No simple Index (viz. Low EF) to rule in the diagnosisNo simple Index (viz. Low EF) to rule in the diagnosis
of HFpEFof HFpEF
1414

Simultaneous & obligatory presence of:Simultaneous & obligatory presence of:
-- Signs and / or symptoms of HFSigns and / or symptoms of HF
-- Evidence of normal EF (EFEvidence of normal EF (EF >> 50%) & LV end diasotlic volume50%) & LV end diasotlic volume
Index < 97 ml / mIndex < 97 ml / m22
-- Evidence of diastolic dysfunctionEvidence of diastolic dysfunction
Emphasis on DD in these guidelines not necessarily implies thatEmphasis on DD in these guidelines not necessarily implies that
DD is the only underlying mechanism of HFpEFDD is the only underlying mechanism of HFpEF
1515
Diagnosis of HFpEFDiagnosis of HFpEF
Presence of DD (grade 2+), along with LA enlargement, anPresence of DD (grade 2+), along with LA enlargement, an
objective way of assessing presence of increased LV fillingobjective way of assessing presence of increased LV filling
pressurepressure Eur Heart J 2012: 33: 1750-7Eur Heart J 2012: 33: 1750-7
Eur Heart J 2007: 28: 2539-50Eur Heart J 2007: 28: 2539-50
Circulation 200: 101: 2118-21Circulation 200: 101: 2118-21

A Normal B-Type Natriuretic
Peptide Does not Exclude the
diagnosis of HFpEF
1616
Key Lesson # 5

 Elevated levels of BNP & NT-Pro BNP are potentElevated levels of BNP & NT-Pro BNP are potent
predictors of adverse outcome in HF regardless ofpredictors of adverse outcome in HF regardless of
underlying EF.underlying EF.
 BNP is less sensitive for diagnosis of HFpEFBNP is less sensitive for diagnosis of HFpEF
compared to HFrEFcompared to HFrEF
Maisel A et al: JACC: 2003: 41:2010-17Maisel A et al: JACC: 2003: 41:2010-17
 BNP levels more accuratelyBNP levels more accurately reflects wall stressreflects wall stress
compared to LV filling pressure. LV wall stress iscompared to LV filling pressure. LV wall stress is
known to be lower in HFpEF than HFrEFknown to be lower in HFpEF than HFrEF..
Iwanaga Y JACC: 2006: 47: 742-8Iwanaga Y JACC: 2006: 47: 742-8
1717

 Up to 30% of patients with HFpEF have BNP levels <Up to 30% of patients with HFpEF have BNP levels <
100 pg/ml despite HF signs & symptoms and invasive100 pg/ml despite HF signs & symptoms and invasive
hemodynamic evidence of elevated LV filling pressurehemodynamic evidence of elevated LV filling pressure
 Obesity, very common with HFpEF, associated withObesity, very common with HFpEF, associated with
low BNP levels.low BNP levels.
 While BNP levels are powerful & independentWhile BNP levels are powerful & independent
predictors of future events in patients with HFpEFpredictors of future events in patients with HFpEF,, aa
normal BNP level cannot exclude the diagnosis ofnormal BNP level cannot exclude the diagnosis of
HFpEF in patients, who have sign & symptoms of HFHFpEF in patients, who have sign & symptoms of HF..
1818
HFpEF :HFpEF : Diagnosis & ManagementDiagnosis & Management
(contd…)(contd…)

Elevated Pulmonary Artery Systolic
Pressure on Echocardiography with a
normal LVEF?
Consider HFpEF
1919
Key Lesson # 6

““Frequency of elevated Pulmonary arteryFrequency of elevated Pulmonary artery
systolic pressure (PASP) among patients withsystolic pressure (PASP) among patients with
HFpEF is 83%”HFpEF is 83%”
LAM et al: JACC: 2009: 53: 1119-26LAM et al: JACC: 2009: 53: 1119-26
 PASP by Doppler Echocardiography a betterPASP by Doppler Echocardiography a better
predictor of HFpEF compared to other echopredictor of HFpEF compared to other echo
parameters associated with DDparameters associated with DD
-- E/e’ ratioE/e’ ratio
-- LA VolumeLA Volume
-- LV wall thicknessLV wall thickness
 If patients with normal EF,If patients with normal EF, elevated PASP iselevated PASP is
suggestive of HFpEF until proved otherwisesuggestive of HFpEF until proved otherwise.. 2020

Use Dynamic Testing to EvaluateUse Dynamic Testing to Evaluate
unexplained Dyspnea or Exerciseunexplained Dyspnea or Exercise
Intolerance when consideringIntolerance when considering
Diagnosis of HFpEFDiagnosis of HFpEF
2121
Key Lesson # 7

HFpEF: Diagnosis & ManagementHFpEF: Diagnosis & Management
A)A) Diastolic Stress TestingDiastolic Stress Testing
Non invasive echocardiographicNon invasive echocardiographic
estimates of LV filling pressures (E/e’)estimates of LV filling pressures (E/e’)
during rest & peak exercise.during rest & peak exercise.
2323

Diastolic Stress TestingDiastolic Stress Testing
Unexplained Dyspnea or Exercise IntoleranceUnexplained Dyspnea or Exercise Intolerance
? HFpEF? HFpEF
Exercise Echocardiography (Measurement ofExercise Echocardiography (Measurement of
E/e’ ratio, PASP at peak stress) &E/e’ ratio, PASP at peak stress) &
Cardiopulmonary exercise testingCardiopulmonary exercise testing
EquivocalEquivocal
Exercise Cardiac CatheterizationExercise Cardiac Catheterization
2424
HFpEF: Diagnosis & ManagementHFpEF: Diagnosis & ManagementHFpEF: Diagnosis & ManagementHFpEF: Diagnosis & Management

Diagnosing HFpEF is ChallengingDiagnosing HFpEF is Challenging
so be thorough and considerso be thorough and consider
invasive hemodynamic testing toinvasive hemodynamic testing to
Confirm the DiagnosisConfirm the Diagnosis
2626
Key Lesson # 8

How to diagnose HFpEF. We propose ‘elevatedHow to diagnose HFpEF. We propose ‘elevated
PCWP during exercise’ as a new criterion forPCWP during exercise’ as a new criterion for
(early) HFpEF(early) HFpEF
2727

Look for CAD in All PatientsLook for CAD in All Patients
with HFpEFwith HFpEF
2828
Key Lesson # 9

 CAD is less prevalent in HFpEF compared to thoseCAD is less prevalent in HFpEF compared to those
with HFrEFwith HFrEF
Yancy CW: JACC: 2006: 47:76-84Yancy CW: JACC: 2006: 47:76-84
 Prevalence of CAD in HFpEF approx 56%Prevalence of CAD in HFpEF approx 56%
Steinberg et al: Circulation 2012:126:65-75Steinberg et al: Circulation 2012:126:65-75
 Presence of CAD is associated with increased risk ofPresence of CAD is associated with increased risk of
developing HFpEF and increased mortality in patientsdeveloping HFpEF and increased mortality in patients
with HFpEFwith HFpEF
Judge K W et al: JACC: 1991: 10: 377-82Judge K W et al: JACC: 1991: 10: 377-82
2929

Conceptual model of pathophysiology linking coronary microvascularConceptual model of pathophysiology linking coronary microvascular
ischemia, low-level cardiomyocyte injury and myocardial stiffness toischemia, low-level cardiomyocyte injury and myocardial stiffness to
major adverse cardiovascular outcomes (MACE), especially heart failuremajor adverse cardiovascular outcomes (MACE), especially heart failure
with preserved ejection fraction. This process may occur even in thewith preserved ejection fraction. This process may occur even in the
absence of obstructive coronary artery or overt structural heart disease.absence of obstructive coronary artery or overt structural heart disease.

 CAD, a treatable condition, symptoms can mimic HF.CAD, a treatable condition, symptoms can mimic HF.
 Systemic evaluation is importantSystemic evaluation is important
 High pretest probability of CAD in HFpEF, negativeHigh pretest probability of CAD in HFpEF, negative
stress test for CAD may not reliably exclude CADstress test for CAD may not reliably exclude CAD
-- Proceed with CAG in all patients with HFpEFProceed with CAG in all patients with HFpEF
unless contraindicatedunless contraindicated
Shah S J et al: Curr Treat options Cardiovasc Med 2010: 12: 58 - 75Shah S J et al: Curr Treat options Cardiovasc Med 2010: 12: 58 - 75
3131
(contd….)(contd….)

Understand the importanceUnderstand the importance
of Heart Rate in HFpEFof Heart Rate in HFpEF
3232
Key Lesson # 10

HR and pathophysiology of HFpEF, a complexHR and pathophysiology of HFpEF, a complex
relationship:-relationship:-
-- Elevated HR is known to be associatedElevated HR is known to be associated
withwith increased mortality andincreased mortality and
hospitalization in HFpEF.hospitalization in HFpEF.
-- Chronotropic incompetence is prevalent inChronotropic incompetence is prevalent in
heart failure & plays important role inheart failure & plays important role in
pathogenesis of HFpEFpathogenesis of HFpEF
3333

-- HR lowering agents suggested to beHR lowering agents suggested to be
beneficial for LV filling bybeneficial for LV filling by increasingincreasing
diastolic filling period. However,diastolic filling period. However,
-- HR response to exercise should beHR response to exercise should be
determined with exercisedetermined with exercise testing intesting in
HFpEFHFpEF
-- If chronotropic incompetenceIf chronotropic incompetence present ratepresent rate
– adaptive pacemaker implantation– adaptive pacemaker implantation should beshould be
considered to improve exerciseconsidered to improve exercise tolerancetolerance
3434
(contd….)(contd….)

Remember the “ZEBRAS”Remember the “ZEBRAS”
when evaluating patients withwhen evaluating patients with
HFpEFHFpEF
3535
Key Lesson # 11

Categorize HFpEF patients into clinicalCategorize HFpEF patients into clinical
phenotypes to help determine the bestphenotypes to help determine the best
management strategy in individualmanagement strategy in individual
patientpatient
3939
Key Lesson # 12

4040
Management of HFpEF by PhenotypeManagement of HFpEF by Phenotype
classificationclassification

It is possible to treat HFpEF –It is possible to treat HFpEF –
Treat by treating underlying co-Treat by treating underlying co-
morbiditiesmorbidities
4141
Key Lesson # 13

Selected Recent or Pending HFpEFSelected Recent or Pending HFpEF
Randomized Controlled TrialsRandomized Controlled Trials
4242

Over the decades the prognosis of HFrEF hasOver the decades the prognosis of HFrEF has
improved significantly but despite the use ofimproved significantly but despite the use of
similar pharmacological agents, prognosis ofsimilar pharmacological agents, prognosis of
HFpEF remains unchanged.HFpEF remains unchanged.
All class of drugs (ACEI, ARB’s, BB, DIG) haveAll class of drugs (ACEI, ARB’s, BB, DIG) have
failed to show significant benefit in Rx offailed to show significant benefit in Rx of
HFpEFHFpEF
4343

““Drug treatment effects onDrug treatment effects on
outcomes in heart failure withoutcomes in heart failure with
preserved ejection fraction: apreserved ejection fraction: a
systematic review and meta-systematic review and meta-
analysis”.analysis”.
Sean Lee Zheng, Fiona T Chan, Adam A Nabeebaccus Ajay MSean Lee Zheng, Fiona T Chan, Adam A Nabeebaccus Ajay M
Shah, Theresa McDonagh, Darlington O Okonko, Salma AyisShah, Theresa McDonagh, Darlington O Okonko, Salma Ayis
Heart 2017; 0; 1-9 doi: 10.1136/heartjnlHeart 2017; 0; 1-9 doi: 10.1136/heartjnl
4444

4545
RCT of pharmacotherapy in HFpEF ofRCT of pharmacotherapy in HFpEF of >> 40% have40% have
been disappointing with no convincingbeen disappointing with no convincing
demonstration of mortality or morbidity reduction.demonstration of mortality or morbidity reduction.
Result of meta-analysis shows significant reductionResult of meta-analysis shows significant reduction
in all cause and CV mortality in RCT usingin all cause and CV mortality in RCT using
betablockers, while RAAS blockade (ACEI, ARB, &betablockers, while RAAS blockade (ACEI, ARB, &
MRA individually) demonstrated no effect onMRA individually) demonstrated no effect on
mortality.mortality.
Improvement in functional outcomes & quality of lifeImprovement in functional outcomes & quality of life
were not significant and consistently demonstrated.were not significant and consistently demonstrated.

HFpEF is a syndrome and not a specific diseaseHFpEF is a syndrome and not a specific disease
process.process.
Overwhelming majority of patients with HFpEF haveOverwhelming majority of patients with HFpEF have
elevated LV filling pressure at rest & / or withelevated LV filling pressure at rest & / or with
exertion.exertion.
Severity of left atrial pressure elevation, volumeSeverity of left atrial pressure elevation, volume
retention and consequent pulmonary hypertensionretention and consequent pulmonary hypertension
with RV dysfunction is variable, as are the aetiologicwith RV dysfunction is variable, as are the aetiologic
& pathophysiologic path by which invididual develop& pathophysiologic path by which invididual develop
HFpEFHFpEF
4646
Key Lesson # 13
“One Size fits all” treatment strategy
is unlikely to work for HFpEF

Theoretical Schema of Heart Failure with PreservedTheoretical Schema of Heart Failure with Preserved
Ejection Fraction patient types, Risk Profiles, and MatchedEjection Fraction patient types, Risk Profiles, and Matched
TherapiesTherapies
4747

““Matchmaking” for optimizingMatchmaking” for optimizing
HFpEF No Laughing MatterHFpEF No Laughing Matter
4848

Sensors, Scissors, Grasper,Sensors, Scissors, Grasper,
Slitter, Cutter & Driller areSlitter, Cutter & Driller are
entering into the managemententering into the management
of HFpEF.of HFpEF.
4949
Key Lesson # 14

CardioMEMS HF System for Pulmonary PressureCardioMEMS HF System for Pulmonary Pressure
Monitoring in Heart Failure Patients Approved by FDAMonitoring in Heart Failure Patients Approved by FDA
5050

LA Strain When EjectionLA Strain When Ejection
Fraction is PreservedFraction is Preserved
5151

Reduce LAP – HF TrialReduce LAP – HF Trial
To evaluate the safety & performance ofTo evaluate the safety & performance of
the Interatrial septal defect system in thethe Interatrial septal defect system in the
treatment of HF patients with elevated LAtreatment of HF patients with elevated LA
pressure despite appropriate medicalpressure despite appropriate medical
treatment.treatment.
Feldman et al; Circulation AHAFeldman et al; Circulation AHA
Nov 2017Nov 2017
5454

““Huffing & Puffing” (dyspnoea & exercise intolerance)Huffing & Puffing” (dyspnoea & exercise intolerance)
are most common symptom.are most common symptom.
““Huff – Puff”Huff – Puff”
““To complain noisily about something but not be ableTo complain noisily about something but not be able
to do anything about it”.to do anything about it”.
Clinician may approach HFpEF with diagnostic &Clinician may approach HFpEF with diagnostic &
therapeutic nihilism & consider there patient astherapeutic nihilism & consider there patient as
untreatable and difficult to manage because of lack ofuntreatable and difficult to manage because of lack of
guidelines & treatment options.guidelines & treatment options.
Diagnosis & treatment of HFpEF requires diligence &Diagnosis & treatment of HFpEF requires diligence &
hypervigilance.hypervigilance. 5959
HFpEF: “Huff Puff”HFpEF: “Huff Puff”

Heart Failure with preserved EF

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