HEART FAILURE WITH REDUCED EJECTON FRACTION

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AMIT SHRIVASTAV
DEFINITION

Common clinical syndrome in which

Clinical syndrome characterized by
symptoms result from a structural or
signs and symptoms of fluid
functional cardiac disorder that
overload and decreased cardiac
impairs the ability of the ventricle to
output
fill with or eject blood.
 EPIDEMIOLOGY
American Heart Association (AHA) estimated that there were 6.2 million people with HF in the United States
between 2013 and 2016 .There are an estimated 23 million people with HF worldwide
Framingham Heart Study found a prevalence of HF in men and women

8/1000 at age 50 - 8 /1000 at 50-59

59 and 66/1000 at and 79/1000 at age
ages 80 - 89 years 80-89

Ho KK, Pinsky JL et al the epidemiology of heart failure: the Virani SS, Alonso A, Benjamin EJ et al Heart Disease and Stroke Statistics-2020 Update: A
Framingham Study. Report From the American Heart Association .
EJECTION FRACTION(EF)
• Ejection” refers to the amount of blood that is pumped out of the heart’s
main pumping chamber during each heartbeat
• “Fraction” refers to the fact that, even in a healthy heart, some blood
always remains within this chamber after each heartbeat
• An ejection fraction is a percentage of the blood within the chamber that is
pumped out with every heartbeat
• Normal EF = 55 to 70 percent
CLASSIFICATION OF LEFT HEART
FAILURE
• Heart failure with reduced ejection fraction(HFrEF) -LVEF <40%
• Heart failure with preserved ejection fraction (HFpEF) – LVEF > 50%
• Heart failure with mid range ejection fraction(HFmrEF) –LVEF – 40-49%
RISK FACTOR FOR HFrEF (First
National Health and Nutrition
Examination Survey) (NHANES I)
13,643 men and women who were followed for 19 years found that the
risk factors for HF

• Coronary heart disease – relative risk 8.1.

• Cigarette smoking – relative risk 1.6.
• Hypertension – relative risk 1.4
• Diabetes – relative risk 1.9.
• Valvular heart disease – relative risk 1.5,

He J, Ogden LG, Bazzano et al Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.
 Common causes of HFrEF
• Coronary artery disease (CAD)
• Myocarditis
• Valvular heart disease
• Infiltrative processes
• Hypertension. After age 40, the lifetime risk of developing HF was twice as
high in subjects with a blood pressure ≥160/100 mmHg compared with
<140/90 mmHg

Lloyd-Jones DM, Larson MG et al Lifetime risk for developing congestive heart failure: the Framingham Heart Study .
PATHOPHYSIOLOGY

Improve or maintain
stroke volume at
Reduction in cardiac first in long term
output and elevated worsening cardiac
pressures. Hypertrophy function.

The heart dilates in Reduced left

response to an ventricular
increase in preload compliance.
to improve
myocardial
contraction (Frank-
Starling mechanism)
PATHO-PHYSIOLOGY
• Upregulation of the renin-angiotensin-aldosterone system
• Activates Angiotensin II and aldosterone
• Vasoconstriction & sodium resorption.
• Epinephrine, norepinephrine, and vasopressin release.
• Increase in heart rate, contractility, and vascular resistance, and vasopressin causes
additional water retention.
• HF Improve initially ,deleterious later.
• Blood pressure increase in afterload, leading to reduced stroke volume and increased
ventricular preload.
• The increase in volume results in hypertrophy and elongation.
• Elevated levels of neurohormones also cause myocyte injury and adversely promote
remodeling.
CLINICAL SIGN AND SYMPTOMS
• Dyspnea
• Paroxysmal nocturnal dyspnea
• Orthopnea
• peripheral edema
• crackles on pulmonary auscultation
• elevated jugular venous pressure,
• S3.
Hunt SA, Abraham WT et al 2009 Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation ,
DIAGNOSIS
• Electrocardiography to evaluate for ischemia and arrhythmia
• Chest radiography to exclude pulmonary causes of dyspnea
• BNP or NT-proBNP assay to establish the presence and severity of
heart failure.
• BNP can effectively differentiate cardiac from pulmonary causes of
dyspnea
DIAGNOSIS
• complete blood count
• Serum electrolytes
• kidney function tests
• Glucose and lipid levels
• Liver chemistry tests
• Thyroid function test
ECHOCARDIOGRAPHY
• primary diagnostic test in the evaluation of heart failure
• provides information on heart size, systolic and diastolic function,
regional wall motion abnormalities
• Regional wall motion abnormalities suggest CAD
• Changes in the myocardium can suggest conditions such as cardiac
amyloid.
• provide prognostic information, particularly in the setting of severely
depressed ejection fraction.
B-type natriuretic peptide (BNP) / N-terminal
pro-B-type natriuretic peptide (NT-proBNP)
Patients at risk for Small studies have
heart failure (such shown that aggressive
as those with guideline-based
BNP assays are hypertension, medical therapy in
typically used to diabetes, or patients with elevated
establish or exclude vascular disease), BNP or NT-proBNP
heart failure as the but without heart levels can help
cause of dyspnea. failure symptoms or prevent future left
left ventricular ventricular
dysfunction, should dysfunction or new-
be screened onset heart failure
B-type natriuretic peptide (BNP) / N-
terminal pro-B-type natriuretic peptide
(NT-proBNP)
BNP levels are
elevated in
Studies have
patients with
Between 100 shown that an
increased right
pg/mL -400 elevated BNP level
or left BNP < 100 is
pg/mL – nor has a sensitivity for
ventricular filling pulmonary
sensitive nor heart failure of
pressures and cause of
specific to 95% to 97% and a
systolic or dyspnea
exclude heart negative predictive
diastolic heart
failure value of 90% to
failure (typically
97%.
>400 pg/mL [400
ng/L])
MANAGEMENT OF HEART FAILURE
• Dietary restriction of sodium (2–3 g daily) and fluid restriction is commonly
recommended in all patients with symptomatic HF, based on the rationale that
sodium and fluid retention are a central aspect of HF pathophysiology

• The body of evidence on which these recommendations are based is relatively

scant, and the level of evidence for fluid restriction in recent guidelines is based
primarily on expert opinion only

• Fluid restriction (<2 L day) should be considered in hyponatremic patients or for

those patients whose fluid retention is difficult to control despite high doses of
diuretics and sodium restriction.

. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of heart failure: a report of
the American college of cardiology`
 PHYSICAL EXERCISE IN HFrEF
• Regular physical activity or exercise training is recommended for HF patients
(class I, level of evidence A) by the current ACC-AHA guidelines.
• HF-ACTION (A Controlled Trial Investigating Outcomes of Exercise Training) was a
large multicenter randomized controlled study of exercise training that enrolled
patients with an EF of 35% or less and (NYHA) class II to IV symptoms with a all-
cause mortality and all-cause hospitalization. In this study, structured exercise
training demonstrated a modest improvement in all-cause mortality and
hospitalization

O'Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009;301:1439–
TREATMENT OF HEART FAILURE
• ACE Inhibitors and Angiotensin Receptor Blockers
• Angiotensin Receptor–Neprilysin Inhibitor
• β-Blockers
• Diuretics
• Digoxin
• Aldosterone Antagonists
• Isosorbide Dinitrate–Hydralazine
• Calcium Channel Blockers
• Ivabradine
• Statins
• Sodium-Glucose Cotransporter-2 Inhibitors
 DRUGS THAT SHOULD BE AVOIDED IN
HFrEF
• NSAIDs- Inhibit the production prostaglandin- Na/H20 retention
• Glitazones – fluid retention
• DPP-4 inhibitor medication – SITAGLIPTIN
• Calcium channel blockers

Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.
LOOP DIURETICS

Diuretics may be Serum potassium

associated with levels should
Loop diuretics are
multiple other generally be
the mainstay of
some studies have metabolic and maintained
treatment for
shown torsemide electrolyte between 4.0 and
volume overload
to be more disturbances, 5.0 mEq/L by
in patients with
effective, which including increasing the
heart failure furosemide is most
may be hyponatremia, dietary intake of
because of the commonly used
attributable to its hypomagnesemia, KCL, although
increased
increased metabolic most patients on
potency of these
bioavailability and alkalosis, significant doses
agents compared
longer half-life. hyperglycemia, of loop diuretics
with other
hyperlipidemia, will require oral
diuretics
and potassium
hyperuricemia. supplementation

G. Michael Felker, M.D., M.H.S et al Diuretic Strategies in Patients with Acute Decompensated Heart Failure
LOOP DIURETICS

Felker GM, Mentz RJ. Diuretics and ultrafiltration in acute decompensated heart failure. J Am Coll Cardiol.
ACE AND ARB INHIBITOR
ACE /ARB INHIBITORS
The observation that vasodilators worsen the heart failure led to the conclusion that
ACE works by mechanism other than decreasing preload/afterload

POSSIBLE MECAHNISM
Inhibition of the adverse
effects of circulating
angiotensin and/or pathological myocardial Decreased
aldosterone on target remodeling hypertrophy
organs such as heart,
blood vessels, and kidney.
ACE/ARB INHIBITORS
The ATLAS trial examined
the effects of low-dose
versus high-dose ACE
ACE inhibitors reduce inhibitor therapy (lisinopril) On the basis of these
morbidity and mortality in in patients with systolic results, the general
patients with HFrEF and are heart failure and found no consensus is to
the cornerstone of long-term difference in overall uptitrate ACE
therapy for both mortality; however, high- inhibitors to maximal
symptomatic and dose lisinopril was doses or until the
asymptomatic patients. associated with a significant onset of symptomatic
reduction in the composite hypotension.
endpoint of mortality and
hospitalizations from heart
failure and for any cause

Milton PackerPhilip A. Poole-Wilson ET AL Comparative Effects of Low and High Doses of the Angiotensin-Converting Enzyme Inhibitor, Lisinopril
ACE /ARB INHIBITORS
Many physicians
do not
recommend
Although ACE
increasing the Patients with pre- Patients who
inhibitors should
dosage once the existing chronic develop cough or
be considered in
creatinine level kidney may angioedema while
every patient with
rises to 2.5 mg/dL develop taking an ACE
HFrEF, elevations
(221 μmol/L) or Hyperkalemia , so inhibitor are often
in creatinine levels
the estimated dose should be switched to an
may prevent use
glomerular reduced ARB
of maximal doses.
filtration rate falls
below 30
mL/min/1.73 m2
ACE /ARB INHIBITORS

The SOLVD Prevention Study, SAVE study, and

Trandolapril Cardiac Evaluation (TRACE) placebo-
controlled trail has shown that
Asymptomatic patients with LV dysfunction have less
remodeling and a reduced risk of progressing to
symptomatic HF when treated with ACE inhibitors.
It has also demonstrated reduction in mortality and
absolute benefit is more in patient with more severe
heart failure
Angiotensin Receptor–Neprilysin Inhibitor

Neprilysin is a
The angiotensin neutral Inhibition of neprilysin
receptor–neprilysin endopeptidase increases levels of
inhibitor (ARNI) that degrades these substances,
valsartan-sacubitril several vasoactive leading to enhanced
belongs to a relatively peptides, including diuresis, natriuresis,
new drug class that natriuretic and myocardial
combines an ARB with peptides and relaxation
a neprilysin inhibitor. bradykinin

John J.V. McMurray, M.D et al Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
MECHANISM OF ACTION
PHARMACOKINETICS
DOSAGE AND ADMINISTRATION

Reduce the starting dose to

24/26 mg (sacubitril/valsartan)
Double the dose after 2 twice-daily for: pts not
The recommended to 4 weeks to the target currently taking an ACEi or an
starting dose is 49/51 maintenance dose of ARB or previously taking a low
mg (sacubitril/valsartan) 97/103 mg dose of these agents
twice-daily. (sacubitril/valsartan)
twice-daily, as tolerated
by the patient. ARNI should not be
administered
concomitantly with ACE
inhibitors or within 36
hours of the last dose of an
ACE inhibitor
PARADISM HF TRAIL
PARADISM HF TRAIL

The largest
clinical trial A double Stopped 6
ever blind trial Head to month early
conducted in randomized head trial due to
heart failure treatment against compelling
( 8442 and single Enalapril not efficacy risk of
patients over blind in dose placebo CV death was
47 countries) tolerability significantly
reduced
 pro BNP/NT PROBNP

John J.V. McMurray, M.D et al Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
John J.V. McMurray, M.D et al Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure
CLINICAL TRIALS IN PIPELINE FOR
ARNI
• PARAGON Trial – HFpEF
• PIONEER Trial – in hospital
• PARADISE – in MI
• PROVE – MOA
• LIFE – Advance HF
BETA BLOCKERS
β-Blockers should be
initiated in all Only three
patients with HFrEF. agents have a
β-Blockers are
β-Blockers improve mortality These agents have
generally well
remodeling, increase benefit negative inotropic
tolerated, but
ejection fraction, (bisoprolol, properties and
they should be
and reduce carvedilol, may exacerbate
initiated only
hospitalization and and heart failure in
when the patient
mortality when metoprolol patients with
is euvolemic or
added to ACE succinate) volume overload.
nearly euvolemic.
inhibitor and diuretic should be
therapy used.
BETA BLOCKERS

Consequently, β- In patients with

blockers should be reactive airways
initiated at low doses disease or COPD, β-
and slowly uptitrated In general, hospitalized blocker therapy
over weeks (not days) patients should be should not be
until the patient started on β-blocker initiated if the
achieves a heart rate therapy before patient has
of around 60/min or discharge. bronchospasm or
has symptomatic evidence of an
hypotension exacerbation of
pulmonary disease.
 BETA BLOCKERS

Milton Packer, M.D., Michael R. et al The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure
J wikstarnd MERIT-HF--description of the trial
Initiating and Managing ACE Inhibitor and β-Blocker Therapy

β-blocker Recent
should be guidelines
Studies have
initiated recommend
shown that ACE inhibitor
first in treating to a
patients receive should be
patients systolic
additive benefit started first in
with CAD blood
from the patients with
or atrial pressure of
second agent diabetes for the
fibrillation less than
regardless of additional renal
who 130/80 mm
which agent is benefits.
require Hg in
started earlier.
heart rate patients with
control. HFrEF.
Ivabradine
In patients with chronic
Ivabradine is a symptomatic heart failure and
sinoatrial node left ventricular ejection
modulator that Approved in
fraction less than or equal to
selectively usa for
35% who are in sinus rhythm
inhibits the patients
and taking maximally
whose heart
If current in the tolerated doses of a β-blocker,
rate> 70 after
sinoatrial node, ivabradine reduces heart
maximum
causing a failure–associated
tolerated dose
reduction in heart hospitalizations and the
rate. mortality and heart failure
hospitalization.
Aldosterone Antagonists

Aldosterone antagonists
(spironolactone,
eplerenone) reduce Current guidelines
mortality and heart recommend these Generally, the doses of
failure hospitalizations agents as first-line both the ACE inhibitor
in patients with therapy, along with and β-blocker should be
symptomatic heart uptitrated to maximal
ACE inhibitors and β- levels before
failure (NYHA functional blockers, in patients
class II-IV symptoms) spironolactone or
and patients with heart with symptomatic eplerenone is added.
failure after an acute heart failure
myocardial infarction
Aldosterone Antagonists

Despite their proven

efficacy, they are Both drugs require In clinical trials, potassium
underused, probably that patients be supplementation was
because of concerns monitored for routinely discontinued at
of hyperkalemia and hyperkalemia, and the beginning of therapy,
associated death these agents should and electrolyte
raised by be used carefully in measurement was
observational studies patients with kidney repeated within 1 week of
of spironolactone. dysfunction initiation.
Digoxin

The use of digoxin in

patients with heart Digoxin is used in patients
failure has with HFrEF and
concomitant atrial Digoxin reduces the risk for
decreased over the hospitalization in patients
past 20 years, fibrillation for rate control
and in patients who with heart failure, and its
primarily because of discontinuation is
its lack of mortality continue to have symptoms
of heart failure despite associated with worsening
benefit and the heart failure symptom. It
dangerous side optimal therapy with ACE
inhibitor and β-blocker doesn’t improve survival
effects associated
with digoxin toxicity. therapies
Isosorbide Dinitrate–Hydralazine

Isosorbide dinitrate–
hydralazine is
superior to placebo This combination
in reducing should be considered
in patients intolerant Headache is a
hospitalization but common adverse
inferior to ACE of ACE inhibitors and
ARBs, especially those effect
inhibitors for
survival benefit in with chronic kidney
patients with disease.
symptomatic HFrEF.
Calcium Channel Blockers

These two
drugs are safe
but should be Other calcium
Amlodipine and
used only in channel blockers
felodipine have
patients with has detrimental
shown neither
hypertension effects in patients
benefit nor harm in
despite with systolic heart
patients with heart
therapy with failure and should
failure.
other agents not be used
at maximal
dosage.
STATINS

Moderate-
intensity statin In addition, HF
therapy can be management is
Two major
considered in The randomized potentially
randomized trials,
patients with trials that have complicated by
CORONA and
heart failure with provided evidence the observation
GISSI-HF, have
reduced ejection of benefit have that low serum
directly addressed
fraction included only few cholesterol is
this issue in
attributable to patients with associated with
patients with
ischemic heart heart failure worse outcomes
systolic HF.
disease if life
expectancy is at
least 3 to 5 years.
STATINS
A similar relationship
Relationship between
between lower serum
lower serum However, a 2014
cholesterol levels and
cholesterol levels (less meta-analysis of 15
higher mortality was
than 200 mg/dL [5.2 studies of a
also found in a
mmol/L] and higher total showed benefit
multivariable analysis
mortality was also of low cholesterol but
of almost 18,000
found in a CORONA and GISSI-HF
patients presenting
multivariable analysis trials were not
with short-term
of 114 patients with included
(acute) heart failure
chronic HF
exacerbations
Rauchhaus M, Clark AL el al The relationship between cholesterol and survival in patients with chronic heart failure
Horwich TB, Hernandez AF et al Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure.
Sodium-Glucose Cotransporter-2 Inhibitors(SGLT2)

• (SGLT2) inhibitors
Empagliflozin
Canagliflozin
Dapagliflozin
Glucagon-like peptide-1 receptor agonists
Liraglutide,
Semaglutide,
Dulaglutide)
Sodium-Glucose Cotransporter-2 Inhibitors(SGLT2)

The 2020 American Diabetes

Association Standards of Care,
endorsed by the ACC, recommends In patients with type 2 diabetes and
an SGLT2 inhibitor in patients with established heart failure, an SGLT2
type 2 diabetes and established inhibitor may be considered to
ASCVD, multiple ASCVD risk reduce the risk for heart failure
factors, or diabetic kidney disease hospitalization
to reduce the risk for major
cardiovascular events and
hospitalization for heart failure.
Inhibitors(SGLT2)
Sodium-Glucose Cotransporter-2 Inhibitors(SGLT2)

The 25% decrease in the risk of the composite of

cardiovascular death and heart failure hospitalization
observed in EMPEROR-Reduced was identical to that
seen in DAPA-HF. Empagliflozin reduced the total
number of hospitalizations for heart failure and
slowed the rate of progression of renal disease.

Taken together, it can be concluded that the

concordant results of DAPA-HF and EMPEROR-
Reduced should be sufficient to establish SGLT2
inhibitors as a new standard of care for patients with
heart failure and a reduced ejection fraction.
Implantable Cardioverter-Defibrillator(ICDs)

Arrhythmias are a common Current guidelines

cause of death in patients recommend ICD placement
with heart failure, and in patients receiving
implantable cardioverter- guideline-directed medical
defibrillators (ICDs) improve therapy who have an
survival when used for both ejection fraction less than
or equal to 35% and NYHA
primary and secondary functional class II or III
prevention of arrhythmias heart failure symptoms
Cardiac Resynchronization Therapy
(CRT)

NYHA functional
Retrospective analysis of class II to IV heart
CRT has improved many trials has shown failure symptoms
ejection fraction, that patients with LBBB despite
reduced heart are most likely to benefit guideline-
from CRT. Based on these directed medical
failure symptoms, therapy, sinus
findings, CRT is indicated
and reduced in patients with an rhythm, and
mortality ejection fraction less than LBBB with a QRS
or equal to 35% complex of 150
ms or greater
Inpatient Management of Heart Failure
Acute Decompensated Heart Failure

On physical
Orthopnea, examination,
paroxysmal jugular venous Signs and symptoms
Perfusion should also
nocturnal distention is of poor perfusion
be assessed, and
dyspnea, usually present. include cool
patients may be
peripheral Patients may have extremities, a narrow
classified as “warm”
edema, weight crackles (much pulse pressure, poor
(adequate perfusion)
gain, and more likely in mentation, and
or “cold” (inadequate
progressive acute than chronic worsening kidney
perfusion)
exertional heart failure), function.
dyspnea. ascites, or
peripheral edema.
Inpatient Management of Heart Failure
A recent study
evaluated Intravenous
Diuretic therapy is the administration of high- inotropes or other
principal treatment for dose diuretics (2.5 advanced therapies
patients with times the outpatient should be
decompensated heart oral daily dosage) was considered in
failure and fluid associated with patients with signs
overload increased diuresis but of poor perfusion
also transient to help improve
worsening of kidney cardiac function.
function.
Inpatient Management of Heart Failure

If a patient
receiving diuretic
Once euvolemia
In patients with withholding ACE therapy develops
worsening kidney, has been
acute kidney inhibitors and
---withholding achieved,
dysfunction at the aldosterone
diuretics for 1 day creatinine often
time of admission, antagonists may be to allow also increases,
it is still important reasonable until extravascular fluid which may
to treat with kidney function to redistribute into indicate
diuretic therapy. improves. the vascular space
should be decongestion.
considered.
Inpatient Management of Heart Failure

BNP level should be measured

upon admission and before
Standard therapy for HF should discharge for prognostic purposes
be initiated because high levels are linked
with increased mortality and
rehospitalization.
Cardiogenic Shock

• Cardiogenic shock is characterized by signs and symptoms of low

cardiac output and end-organ compromise, with acute worsening of
kidney and liver function
• Patients with cardiogenic shock often require intravenous inotropic
agents
Chronic Heart Failure

• Clinical indicators associated with worse outcomes in the 1 to 2

years after diagnosis include heart failure hospitalization
• Poor exercise tolerance
• ICD firings
• Serum sodium level less than 135 mEq/L
• Worsening kidney function
• Cardiac cachexia, required diuretic doses of more than 1 mg/kg,
• Symptomatic hypotension necessitating reduction in the dosage of heart
failure medications.
• Serial B-Type Natriuretic Peptide Assessment and treatment has shown
reduction in mortality