Heart

Failure

Heart failure (HF)

A pathological condition in which heart is
unable to pump enough blood to the rest
of the body
-unable to fill with a sufficient volume of
blood
-unable to generate sufficient force to
pump out enough blood

Ejection Fraction refers to the fraction of

blood the heart pumps out with each beat

LUNGS
PV

SVC
IVC
RA

RV
LUNGS

PA

LA

LV
LVH
Aorta

Loss of elasticity
Decline in pumping action

Myocardial
Ischemia

Hypertensio
n

Cardiomyopath
y

Valvular Heart
Disease

Decreased Cardiac
Output
Carotid Baroreceptor Stimulation Decreases
Renal Perfusion Decreases

Activation ofsystems
SNS and are activated in the
Thus, 2 major compensatory
RAAS
body:
1. Sympathetic Nervous System (SNS)
Increaseangiotensin
Heart Rate and aldosterone
Vasoconstriction
Increases afterload
2. Renin
system
(RAAS)
Inotropy
Hemodynamic alterations Increases
Myocardial Toxicity

preload

Negative Remodeling
Worsened LV Function

Symptoms of HF

What are the cardinal symptoms

of HF?

Fatigu
e

Dyspnea

Classification
NYHA Functional Classification

ACCF/AHA Stages of HF
A

At high risk for HF but without

structural heart disease or
symptoms of HF

Structural heart disease but

without signs or symptoms of HF

Structural heart disease with

prior or current symptoms of HF

Refractory HF requiring
specialized interventions

No limitation of physical activity.

Ordinary physical activity does
not cause symptoms of HF.

II

Slight limitation of physical

activity. Comfortable at rest, but
ordinary physical activity results
in symptoms of HF.

III

Marked limitation of physical

activity. Comfortable at rest, but
less than ordinary activity
causes symptoms of HF.

IV

Unable to carry on any physical

activity without symptoms of HF,
or symptoms of HF at rest.

Based on Left Ventricular Ejection Fraction

(LVEF):
1.Systolic HF or Systolic dysfunction
Defect in ventricular contraction

Left ventricle loses ability to generate enough pressure to

eject blood forward into the aorta

Some patients with systolic HF have associated

Decreased LVEF <35 or 40%
diastolic dysfunction therefore, in most cases,
diastolic & systolic HF are not considered as
2. Diastolic HF orseparate
Diastolicentities
dysfunction

Impaired ability of ventricles to fill

Patients have symptoms and/or signs of HF

Preserved or abnormal LVEF >40-50%

Based on Main Site of Congestion:

1. Left-sided HF: Most common
Back up of blood into the left atrium and pulmonary veins

Result: Pulmonary edema/ Pulmonary congestion

Fatigue
Dizziness
Dyspnea
Rales
Coughing

2. Right-sided HF

Unresolved left-sided HF eventually leads to right sided HF

Backward flow of blood into the right atrium and venous

circulation

Result: Systemic edema

Jugular vein distention

Pedal edema
Ascites
Hepatomegaly
Weight gain

Right Heart Failure

Peripheral fluid overload

Left Heart Failure

Pulmonary fluid overload

How to diagnose HF?

o
o
o
o
o
o

History and physical examination

2-Dimenional doppler echocardiography
Chest X-ray
Exercise test
Electrocardiography (ECG or EKG)
Laboratory tests - Complete blood count, Serum
electrolytes (sodium and potassium), Blood
urea nitrogen (BUN), Liver function tests,
Thyroid-stimulating hormone, Biomarkers

Biomarkers
Natriuretic peptides BNP or NT-pro BNP
- Released from cardiomyocytes due to numerous triggers mostly,
myocardial stretch

- Diagnosis or exclusion of HF in the setting of chronic ambulatory HF

- Presence and severity of HF
- Prognosis of HF

Cardiac Troponin T or I
- Abnormal levels due to myocyte injury or necrosis often without presence
of MI or underlying CAD

- Impaired hemodynamics, progressive LV dysfunction and increased

mortality rates

Galectin-3
- Additive to natriuretic peptide levels

How to manage HF?

Relief from signs and symptoms
Sodium restriction (<3 g/d), Diuretics, Digoxin

Improve survival
ACEI/ ARB, Beta-blocker, Aldosterone
antagonist
ICD, CRT + ICD, Hyd/ ISDN
Aspirin, Warfarin, Statin

Diuretics
Inhibits reabsorption of sodium or chloride at specific sites in
renal tubules; improves dyspnea and peripheral edema
Used in conjunction with ACEI, beta-blocker and an
aldosterone antagonist
Therapy is commonly initiated at low doses and dose is
increased until urine output increases and weight decreases
(0.5-1 kg daily)
Hypovolemia, Hyponatremia, Hypokalemia Increase risk of
hypotension and renal dysfunction
Preferred diuretics - Loop diuretics (torsemide, furosemide)
Thiazide diuretics (hydrochlorthiazide, chlorthalidone)
Hypertensive patients with HF and mild fluid retention
Combination can be used in patients with resistant edema

Beta-blockers
Recommended in all stable HF patients with reduced EF
(Class I, LOE A); reduce risk of death and hospitalization
Lessen the symptoms, improve patients clinical status,
and enhance overall well-being
Benefits seen in patients with or without CAD, with or
without diabetes as well as in women and black
Favorable effects in addition to ACEIs
Patients with fluid retention, beta-blockers should not be
taken without diuretics
E.g. carvedilol, metoprolol extended release

Angiotensin converting
enzyme inhibitors (ACEIs)
Reduces risk of death and hospitalization
Benefits seen in patients with mild, moderate or severe
symptoms of HF and in patients with or without CAD
Used in all patients with a reduced LVEF (<35% to 40%)
(Class I, LOE A)
Therapy initiated at low dose followed by gradual dose
increments
Should be used with a -blocker
Most common side effects hypotension, hyperkalemia,
angioedema and cough
E.g. ramipril, enalapril, lisinopril

Angiotensin receptor
blockers (ARBs)
Recommended in patients
- as an alternative who are intolerant to ACEIs (Class I, LOE
A)
- as an alternative to ACEIs as a first-line therapy in
patients already taking ARBs
Can be considered in patients on ACEIs and beta-blockers
but aldosterone antagonist is not indicated or tolerated
ACEI, ARB and aldosterone antagonist should not be
combined
Side effects include hypotension, hyperkalemia
E.g. telmisartan, candesartan, losartan

Aldosterone antagonists
Aldosterone promotes sodium retention, electrolyte
imbalanced, vascular remodeling and myocardial
hypertrophy
Used in patients with LVEF 35% and severe HF to reduce
mortality and morbidity (Class I, LOE A);
Should be added to all patients on ACEIs (or ARBs) or a
beta-blocker
Major side effect hyperkalemia
E.g. spironolactone, eplerenone

Ivabradine
Inhibits If channel in the sinus node
Slows the heart rate in patients in sinus
rhythm (does not slow the heart rate in
AF)

Digoxin

Mild inotropic effect

Improves symptoms, quality of life and exercise

tolerance in mild to moderate HF but not survival

Added in case of persistent symptoms

Not recommended as a first line therapy, used in HF

patients with AF but beta-blockers are usually more
effective

Major side effects include cardiac arrhythmias, GI

symptoms (anorexia, nausea, vomiting) and neurologic
complaints

Hydralazine and
isosorbide nitrate
Hydralazine produces arterial vasodilation and reduction
in systemic vascular resistance
Nitrates produce arterial and venous vasodilation
Considered in patients with EF 45% despite treatment
with a beta-blocker, ACEI (or ARB) and a aldosterone
antagonist
Combination therapy enhances survival and decreases
hospitalization (in blacks)
Side effects - Hypotension and headache

Anticoagulants
Platelet activation and hypercoagulability in HF
Warfarin therapy has shown to reduce risk of stroke
However, available data suggests that the risk of bleeding
overshadows its benefit in HF patients with sinus rhythm
Large trials are needed to establish the role of antithrombotics in HF patients with sinus rhythm

Inotropes
Reserved for patients with HF refractory to other
therapies
Should be considered in systolic dysfunction who have
low cardiac index and evidence of systemic hypoperfusion
and/ or congestion
May increase risk of morality because of increased
myocardial oxygen consumption and increased
tachycardia effect
Lower doses are preferred
E.g. intravenous dopamine, dobutamine, milrinone and
levosimendan

Non-pharmacological
management
o
o
o
o
o
o

Implantable cardioverter defibrillator (ICD)

Cardiac resynchroization therapy (CRT)
Valvular surgery
Coronary revascularization
Left ventricular assist device
Heart transplantation

Implantable cardioverter
defibrillator

Reduces risk of serious rhythm problems in ventricles, the

primary cause of sudden cardiac death (SCD)

Recommended as a primary prevention to reduce mortality

in patients with LV dysfunction, LVEF 35%, NYHA class II
or III, Stage C HFrEF (Class I, LOE A)

Not warranted in stage D or class IV patients

Cardiac resynchronization
therapy (CRT)
Also called as biventricular pacing
It not only functions as a pacemaker but it re co-ordinates
(resynchronizes) the beating of the two ventricles by
pacing both simultaneously and specifically improving the
contraction of left ventricle
Thus, improving symptoms of heart failure and prolongs
survival
Recommended for NYHA class III or IV; Stage C

Coronary
revascularization
CABG and PCI are considered in patients with CAD
These procedures may lead to symptomatic
improvement and potentially increase cardiac
function

Coronary Artery
Bypass Graft

Percutaneous
Coronary

Valvular surgery

Valvular disease may cause or aggravate HF

Surgical aortic valve replacement
Transcatheter aortic valve replacement
Transcatheter mitral valve repair or mitral valve
surgery

Heart transplantation
Indicated for stage D HF patients despite device ad
surgical management (Class I, LOE C)

Artificial Hearts
Typically used to bridge the time toheart transplantation,
or to permanently replace the heart in case
transplantation is impossible
Can dramatically improve symptoms of late-stage HF, and
sometimes even provide long-term treatment

Mechanical circulatory
devices (MCS)
Stage D patients
Ventricular assist devices
Long term strategies bridge to transplantation, bridge to
candidacy and destination therapy
MCS facilitates LV reverse remodelling

LCZ696
Orally active angiotensin receptor neprilysin inhibitor
(ARNI)
Intended as first line treatment for patients with chronic
HF (NYHA stage II-IV) and reduced LVEF; administered 200
mg twice daily
LCZ696 enhances myocardial relaxation & reduced
ventricular hypertrophy

J Am Coll Cardiol HF. 2013;1:120

PARADIGM-HF: Cardiovascular Death or Heart

Failure Hospitalization (Primary Endpoint)

Kaplan-Meier Estimate of
Cumulative Rates (%)

40

Enalapril

32

(n=4212)

914

24

LCZ696
(n=4187)

16

HR = 0.80 (0.73-0.87)
P = 0.0000002
Number needed to treat = 21

8
0

180

360

540

720

900

1080

1260

896
853

249
236

Days After Randomization

Patients at Risk
LCZ696
Enalapril

1117

4187
4212

3922
3883

3663
3579

3018
2922

2257
2123

1544
1488

N Engl J Med 2014; 371:993-1004

PARADIGM-HF: Effect of LCZ696 vs Enalapril on

Other Endpoints
LCZ696
(n=418
7)

Enalapril
(n=4212
)

Hazard
Ratio
(95% CI)

P
Value

Cardiovascular
death

558
(13.3%)

693
(16.5%)

0.80
(0.710.89)

0.00004

Hospitalization
for heart
failure

537
(12.8%)

658
(15.6%)

0.79
(0.710.89)

0.00004

All-cause
mortality

711
(16.9%)

835
(19.8%)

0.84
(0.760.93)

< 0.0001

N Engl J Med 2014; 371:993-1004

Seralaxin
A recombinant form of the human hormone
relaxin
RELAX-AHF trial
May be potentially a attractive option for
patients with acute HF

Cardiac myosin activators

Omecamtiv mecarbil
Increases cardiac output and stroke volume
Suggest a new therapeutic target in HFrEF

Stem cell therapy

Biological cells that can divide and differentiate into

diverse specialized cells

Several trials have shown that

adult stem cell therapy is safe,
effective and equally effective in
treating infarcts. The possible
mechanisms include:
generation of cardiomyocytes
and stimulation of growth of
new blood vessels.

Gene Therapy
Replacing a faulty gene with a
normal one
Viral vectors carrying the
correct gene bind to a receptor
on the cardiac myocytes,
travel to the nucleus where the
gene is incorporated into the
genome & transcription occurs
Can be used along with stem
cell therapy to increase
benefits

J Am Coll Cardiol HF. 2013;1:120