eart Failure

evelops as a
sult of decreased
ardiac output,
hen the heart
ecomes unable to
rovide adequate
mount of blood to
he organs according
their needs.

Activated Compensatory Mechanisms

to Maintain Adequate CO

First Line Response: sympathetic nervous system activation:

least effective, release epinephrine and norepinephrine
heart rate (HR), myocardial contractility and peripheral
vasoconstriction
Overtime-detrimental- failing myocardiums need for
oxygen and workload

overtime: CO renal blood flow RAAS

Renin + Angiotensinogen
Angiotensin I
Angiotensin II
Peripheral
Vasoconstrictio
n

Aldosterone Secretion

Myocardial
hypertroph
y

Fibrosis

Salt & Water Retention

Plasma Volume

Afterload
Cardiac Output

Kaliuresis

Preload
Cardiac Workload

Heart Failure

Edema

Proinflammatory cytokines (e.g., TNF, ILs) and endothelin1

Released by cardiac myocytes in response to cardiac injury
or stress
Depress cardiac function cardiac hypertrophy,
contractile dysfunction, and myocyte cell death

Counter regulatory processes

Natriuretic peptides: atrial natriuretic peptide (ANP) and btype natriuretic peptide (BNP)- *also test for diagnosis
Released in response to atrial volume and ventricular pressure
Promote venous and arterial vasodilation reduce preload
and afterload
Enhance diuresis
Natriuretic peptides- endothelin and aldosterone antagonists
(block effects of RAAS activation)
Natriuretic peptides- inhibit development of cardiac
hypertrophy and may have anti-inflammatory effects
Prolonged HF > depletion of these factors

Definition-Heart Failure
Key Concepts

CO = SV x HR-becomes insufficient to meet

metabolic needs of body
SV- determined by preload, afterload and
myocardial contractility
Usually reduced ejection fraction (EF) in heart
failure (< 40%)

Preload
Volume of blood in ventricles at end diastole (relaxation)
Depends on venous return
Afterload
Force needed to eject blood into circulation
Depends on peripheral vascular resistence
Valvular disease increases afterload

90/140= 64% EF- 55-65 (75)

Types of Heart Failure

Systolic (or squeezing) heart failure (contractility)

Impaired ability of the heart to contractCO
Weakened muscle, enlarged heart size
Decreased ventricular ejection fraction (EF)
Diastolic (or relaxation) heart failure ( ventricular
filling)
Involves a stiff, thickened heart muscle
Inability of heart to fill
Elevated left or right ventricular end-diastolic pressures
May have normal EF
Mixed

Left-Sided Heart Failure

Left Ventricle is weakened or overloaded

Right-Sided Heart Failure

Right Ventricle is impaired

Results in systemic venous overload

Seen with pulmonary hypertension, large RV

infarctions.

10

Jessup, NEJM 2003

Acute HF (MI, worsening valvular defect)

sudden onset with associated signs and
symptoms
Chronic HF
secondary to slow structural changes occurring
in the stressed myocardium
Acute Decompensated or Refractory HF
sudden exacerbation of symptoms in chronic
heart failure
12

Risk Factors for Heart Failure

Coronary artery disease

Hypertension LVH
Valvular heart disease
Congenital heart defects
Inflammation of Heart muscle (myocarditis, cardiomyopathy)
Abnormal heart rhythms
Diabetes and dyslipidemia
Hyper or hypothyroidism
Others (obesity, age, smoking, anemia, obstructive sleep
apnea, diet, drugs)

Signs & Symptoms

Left Ventricular Failure
Subjective Weakness, fatigue and
dysnea (reduced physical
exertion)
S3 gallop
Shortness of breath (SOB),
wheezing
Orthopnea, paroxysmal
nocturnal dyspnea,
tachypnea and cough
Fluid overload (pulmonary
congestion and peripheral
edema)

Right Ventricular
Failure
Peripheral Edema
Fatigue, weakness,

lethargy
Hepatomegaly (liver
engorgement)
Ascites
Elevated neck veins

Signs & Symptoms

Left Ventricular Failure

Objective

Right Ventricular Failure

LVH, HR, BP, EF(<40%) Wt gain (fluids)

BUN (BUN:creatinine >20) Elevated jugular
venous pressure
May be normal EF

Complications

High risk of fatal dysrrhythmias (e.g. ventricular

tachycardia, sudden cardiac death) with EF <35%

HF lead to severe hepatomegaly, especially with RV

failure
Fibrosis and cirrhosis - develop over time
Renal insufficiency or failure

Diagnosis

Chest X-ray
Blood tests (cardiac enzymes, BNP, electrolyte, renal
function, blood picture)
Electrocardiogram (ECG) IHD, block or conduction
abnormalities in dilated cardiomyopathy
Echocardiogram (Echo) EF, structural, valvular
abnormalities
Coronary arteriography in chest pain or angina
Exercise testing should be part of initial evaluation of
all patients (NYHA HF Classification)

But

Cardiomegaly

Pulmonary Edema due to Heart

Failure

Classification of Heart Failure

ACCF/AHA Stages of HF
A At high risk for HF but
without structural heart
disease or symptoms of HF.

NYHA Functional Classification

None

Structural heart disease but

without signs or symptoms
of HF.

Structural heart disease with I

prior or current symptoms
of HF.
II

D Refractory HF requiring
specialized interventions.

No limitation of physical activity. Ordinary physical

activity does not cause symptoms of HF.
No limitation of physical activity. Ordinary physical
activity does not cause symptoms of HF.
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.

The New York Heart Association (NYHA) classification system is based largely on the assessment of symptoms. 1
The new American College of Cardiology and American Heart Association (ACC/AHA) classification guidelines were designed to
compliment the NYHA classification system. These new guidelines focus more on underlying disease and the need to treat early in
the disease process, even before overt symptoms of heart failure are present. 2

ACC/AHA heart
failure (HF)
staging system

Treatment of Heart Failure

2013 ACC/AHA Guidelines for the Management of Heart

Failure
Diuretic, ACE inhibitor, -blocker & sometimes as
fourth drug digoxin
Aldosterone antagonist in advanced HF

Objectives of Therapy
Treatment of underlying
disorders or precipitating
factors
Control symptoms
Avoid complications
(arrhythmias)
Improvement of quality of life

Non Pharmacological Management

Lifestyle Changes
Physical activity
Weight reduction (daily weight)
Sodium restricted diet
Smoking
Supportive stockings

Physical Activity is essential to improve tissue perfusion

Graded exercise program can help reduce stress and
blood pressure
Weight Reduction is imp as extra weight can put a
strain on the heart
At acute exacerbation of heart failure: bed rest & lower
physical activity is imp to decrease cardiac metabolic
demands

Sodium-Restricted Diet:
1 g Na =2.5 g NaCl, 1 teaspoon=6 g NaCl
A low sodium diet (2-2.5 g daily) is recommended for most
hospitalized HF patients (sodium is bad for high blood
pressure and causes fluid retention)
Restricted salt can aid diuretic action and lower its dose
In patients with recurrent or refractory volume overload,
stricter sodium restriction may be considered.

Fluid restriction (1.5 to 2 L/d) is recommended in patients

with moderate hyponatremia (serum sodium < 130 mEq/L)
In patients with severe (serum sodium < 125 mEq/L) or
worsening hyponatremia, stricter fluid restriction may be
considered.
Should be considered to assist in treatment of fluid overload in
other patients.
*Weight gain of 1.4 kg over 2 days or 2-3 kg gain over a weekindicates fluid overload
Routine administration of supplemental oxygen is
recommended only in the presence of hypoxia or dyspnea.
Smoking cessation is important due to its detrimental effect
on heart and blood vessels

Main Goal of Pharmacological

Therapies

Diuretics
Diuretics inhibit sodium and water retention venous
pressure cardiac preload efficiency of the heart as
a pump cardiac output congestive features of
edema in lungs and periphery

Low-grade: thiazides --- hydrochlorothiazide

Higher-grade : loop diuretics --- furosemide

Diuretics
Diuretics are recommended when clinical evidence exists
for volume overload or fluid retention
As-needed diuretic depends on wt gain changes, neck
vein distention or SOB (If wt gain >0.5-1 kg/day or 2
kg/week wt gain/swollen legs, restart diuretic)
Diuretics can relieve peripheral & pulmonary edema within
hours or days unlike other agents (ACEIs/-blockers) that
require weeks to months

Diuretics
DIURETIC MONOTHERAPY
IS NOT ALLOWED as they offer ineffective maintenance
alone
Diuresis-induced hypovolemia activates RAA & sympathetic
NS aggravates HF progression
Loop diuretics such as furosemide, bumetanide, and
torsemide are preferred first-line diuretics because of
efficacy in patients with and without renal impairment
(effective even at creatinine Clcr is less than 5 mL/min)
Loop diuretics induce a prostaglandin-mediated increase in
renal blood flow that contributes to their natriuretic effect

Diuretics in Hospitalized Patients

If patients are already receiving loop diuretic therapy, the initial
IV dose should equal or exceed their chronic oral daily dose
Diuretic dose should be adjusted accordingly to relieve
symptoms, reduce volume overload and avoid hypotension.
Daily serum electrolytes, urea and creatinine concentrations
should be measured

When diuresis is inadequate to relieve symptoms, it is

reasonable to intensify the diuretic regimen using either:
higher doses of intravenous loop diuretics.
addition of a second (e.g., thiazide) diuretic.
Additional low-dose dopamine infusion may be considered to improve
diuresis, better preserve renal function and renal blood flow.
Refer for hemodialysis, ultrafiltration or other renal replacement
strategies if diuresis is impeded by renal insufficiency

Diuretic Therapy Monitoring

CHF symptoms should be lowered

Wt Loss (ideal loss is 0.5-1 kg/day), disappearance of S3
gallop and decreased peripheral edema (JVP)
Signs of volume depletion: hypotension, dizziness,
weakness, decreased urine output and raised BUN
Check serum K+, Mg2+, uric acid & glucose

Diuretics Adverse Effects

Hypokalemia

Furosemide produces hypokalemia

Initial serum K+ before therapy is considered
Patients on digoxin are more sensitive to hypokalemia (toxicity)
Hypokalemia takes several weeks to go to normal after diuretic
withdrawal
K+ replacement: Only KCl should be used because all
hypokalemic diuretics can cause hypochloremic alkalosis

Angiotensin-converting-enzyme inhibitor (ACEI )

Captopril Enalapril Lisinopril Quinapril
Ramipril Fosinopril Perindopril
ACE inhibition
bradykinin levels
Ag II peripheral resistance afterload cardiac
output
aldosterone Na and water retention preload
aldosterone and AgII remodelling of heart, myocardial
fibrosis, myocyte apoptosis and cardiac hypertrophy
NE release as angiotensin facilitates the release of
norepinephrine from sympathetic nerve endings

ACE inhibitors are administered in lower doses alone or

together with other agents in all stages of CHF, due to systolic
dysfunction.
Continue/start even in mild to moderate renal failure without
hyperkalemia as renal failure will likely resolve with increased
perfusion.

Precautions
Avoid all nonsteroidal anti-inflammatory drugs because
they block the effect of ACE inhibitors and diuretics.
Avoid CCBs (only safe CCB in heart failure is amlodipine)
Cough and angioedema are the most common causes of
ACE inhibitor intolerance. In those patients, use ARBs like
valsartan, irbesartan, candesartan
ARBs are not alternatives in patients with hypotension,
hyperkalemia or renal insufficiency due to ACE inhibitors

Aldosterone antagonists
Spironolactone and eplerenone
block the mineralocorticoid receptor, the target site for
aldosterone action Na and water retention
Both ANGII & aldosterone have direct CV detrimental effects:
vascular & myocardial hypertrophy & fibrosis,
direct vascular & endothelial damage,
increased oxidative stress
In cases of severe heart failure, low-dose spironolactone may
be added to a patient's regimen with symptoms at rest
despite therapy while regularly checking creatinine and
electrolyte (K) levels
Spironolactone addition to maintenance HF therapy,
significantly reduced mortality in severe HF (NYHA III-IV)

 In low doses, spironolactone potentiates the effects of

ACE inhibitors.
Spironolactone is a weak diuretic and has antiarrhythmic
activity.
Spironolactone prevents myocardial fibrosis, caused by
aldosterone, and in this way increases myocardial
contractility.
Similar to spironolactone is another aldosterone
antagonist Eplerenone.

Beta Blockers

Certain Beta blockers (carvedilol, metoprolol, bisoprolol)

can improve disease progression, decrease hospitalizations,
and reduce mortality in patients with HF NYHA class II to III
Mechanism of their beneficial actions
antiarrhythmic effects
renin release RAAS
decreasing heart rate and ventricular wall stress and
thereby reducing myocardial oxygen demand
decreasing myocyte death from catecholamineinduced necrosis or apoptosis

Initiation of beta-blocker therapy is recommended after

optimization of volume status and discontinuation of
intravenous diuretics, vasodilators or inotropic agents.
Beta-blocker therapy should be initiated at low dose and only
in stable patients.
Contraindicated:
Heart rate <60 bpm
Signs of peripheral hypoperfusion
COPD, asthma
PR interval > 0.24 sec, 2 nd or 3rd degree block

Digoxin
Digoxin provides symptomatic benefits and exercise
tolerance in patients with mild to moderate HF but does not
improve survival in patients with HF
Digoxin increases the heart's ability to contract (positive
inotropic effects), however, its benefits in HF are mainly
related to its neurohormonal effects
Mechanism of its positive
inotropicity:
Na K ATPaseNai Na
Ca exchanger Cai
contractility

Digitalis increases the stroke

volume and hence CO
No increase in oxygen consumption
Neurohormonal effects
Digoxin attenuates the excessive sympathetic nervous system
activation in HF by central sympathetic outflow and improving
impaired baroreceptor function.
Digoxin also increases parasympathetic activity in HF patients
heart rate diastolic filling.

 In patients with HF and supraventricular tachyarrhythmias

such as atrial fibrillation, digoxin should be considered
early in therapy to control ventricular response rate.
Digoxin is used together with standard HF therapies (ACE
inhibitors, -blockers and diuretics) in patients with
symptomatic HF to reduce hospitalizations.
Contraindications: bradycardia, AV block, extrasystoles
arrhythmias.

 Hypokalemia and hypercalcemia potentiate the action of digoxin

and increase its toxicity (N, V, arrhythmiascardiac arrest)
Digoxin produces gradual effects over several hours (need
higher loading dose then maintenance dose)
In the absence of supraventricular tachyarrhythmias, a loading
dose is not indicated
Blood samples for measuring plasma digoxin concentrations
should be collected at least 6 hours, and preferably 12 hours or
more, after the last dose.
Specific antidote for digitalis intoxication are Digoxinspecific Fab-antibody (Digoxin Immune Fab) in the form
of intravenous infusion.

Vasodilators

Dilation of veins decreases preload

Dilation of arteries decreases afterload
Decrease work load and oxygen demand of heart
Nitrate esters: ISDN, Sodium nitroprusside (selective vein
dilation)

Hydralazine (selective arterial dilation)

Prazosin - receptor blocker (both arteries and veins)

In the absence of symptomatic hypotension, intravenous

vasodilators (intravenous nitroglycerin or nitroprusside) and
diuretics are recommended therapy for rapid improvement of
congestive symptoms in patients admitted with acute
decompensated heart failure.
These agents should be decreased in dosage or
discontinued if symptomatic hypotension or worsening renal
function develops.

Inotropes
Short-term i.v. inotropic support may be reasonable in
hospitalized patients with severe systolic dysfunction or
cardiogenic shock (BP and CO) to maintain systemic
perfusion and preserve end-organ performance.
+ve inotropism via - adrenergic agonists (e.g.
1
dobutamine) or via inhibition of myocardial
phosphodiesterase III, the enzyme responsible for cAMP
degradation (e.g. Amrinone, and Milrinone)

Long-term, continuous intravenous inotropic support may

be considered for symptom control in decompensated
patients (stage D) who are not eligible for either medical
therapy or cardiac transplantation.
Long-term use of parenteral positive inotropic agents, in the
absence of specific indications, is potentially harmful in the
patient with HF (oxygen demand and causes lifethreatening arrhythmias on chronic use)

Metabolic cardioprotective agents

Trimetazidine increases ATP synthesis and decreases
acidosis in ischemic tissues.
Levocarnitine has antioxidant activity and increases ATP
synthesis. It is indicated in cardiomyopathy caused by
carnitine deficiency.
Preparations containing Coenzyme Q10 stimulate ATP
synthesis and improve myocardial contractility in CHF.
Calcium sensitizers (Levosimendan) increases sensitivity of
troponin in the heart to calcium myocardial contractility
(used as i.v. infusion for short treatment of severe heart
failure)

Arginine Vasopressin Antagonists

Vasopressin antagonists (short term use) improve serum
sodium concentration in patients hospitalized with volume
overload and persistent severe hyponatremia despite water
restriction and maximization of therapy
Its use is CI in patients with pre-existing liver disease
Other drug options include nesiritide preparation of
human BNP that mimics the action of endogenous BNP,
causing diuresis and vasodilation BP cardiac output.

Venous Thromboembolism Prophylaxis

in Hospitalized Patients
Decompensated hospitalized HF patients should be treated
for venous thromboembolism prophylaxis with an
anticoagulant medication.

Surgical Interventions and Devices

Surgeries
Coronary artery bypass grafting ( revascularization)
Percutaneous coronary intervention (Angioplasty)
Valve replacement
Heart transplantation
Devices
Implantable Cardioverter-Defibrillator
Biventricular pacing device
Left ventricular assist device

Implantable Cardioverter-Defibrillators
for HF

Patients with ischemic or nonischemic

cardiomyopathy, NYHA class II to III HF, and
LVEF 35% have a significant survival
benefit from an implantable cardioverterdefibrillator (ICD) for the primary prevention
of sudden cardiac death from ventricular
fibrillation
ICD placement is not recommended in
chronic, severe refractory HF when there is
no reasonable expectation for improvement
or in patients with a life expectancy of less
than 1 year.

Device
Shown:
Combination
Pacemaker
&
Defibrillator

Biventricular Pacing Device

Abnormal ventricular conduction resulting in a mechanical

delay and dysynchronous contraction

57

 Biventricular pacing device may be

considered for patients with
AF with widened QRS interval ( 120 ms)
severe LV systolic dysfunction (LVEF
35%) who have persistent, moderate to
severe HF (NYHA III) despite optimal
medical therapy.

Cardiac Resynchronization
Therapy (CRT)
Standard implanted pacemakers equipped to specific regions of
heart (usually at positions A and C).
Sometimes a third lead (to position
B) that is designed to conduct
signals directly into the left ventricle.
Combination of all three lead
synchronized pumping of
ventricles efficiency of each beat
pumping

Newer Generation Artificial

Hearts

2013 ACCF/AHA Guidelines for Management

of Heart Failure

Recommendations for Treatment of

Stage A HF
Identifying and modifying risk factors to prevent development of
structural heart disease and subsequent HF.
Strategies include smoking cessation and control of hypertension,
diabetes mellitus, and dyslipidemia according to current treatment
guidelines.
ACE inhibitors or ARBs should be strongly considered for
antihypertensive therapy in patients with multiple vascular risk
factors.

Recommendations for Treatment of

Stage B HF
In patients with reduced EF and with or without history of MI
and, ACE inhibitors or ARBs and beta blockers should be used
to prevent HF
In patients with MI, statins should be used to prevent HF
Blood pressure should be controlled to prevent symptomatic HF,
in the absence of history of MI or ACS
An ICD is reasonable in patients with post-MI, have an LVEF 30%,
and on medical therapy
Nondihydropyridine calcium channel blockers may be harmful
in patients with low LVEF

Pharmacological Therapy for Management of

Stage C HFpEF

Diuretics should be used for relief of symptoms due to volume

overload
Use of -blockers, ACE inhibitors or ARBs for hypertension
in HFpEF
Coronary revascularization for patients with CAD where
angina or demonstrable myocardial ischemia is present
despite therapy

Pharmacological Therapy for Management

of Stage C HFrEF
ACE Inhibitors: ACE inhibitors are recommended for all
patients with HFrEF
ARBs: ARBs are recommended in patients with HFrEF
who are ACE inhibitor intolerant
Diuretics: Diuretics are recommended in patients with
HFrEF with fluid retention
Beta Blockers (bisoprolol, carvedilol or metoprolol) is
recommended for all stable patients (proven to reduce
mortality)

Pharmacological Therapy for Management

of Stage C HFrEF
Aldosterone receptor antagonists are recommended in
patients with NYHA class II-IV HF who have LVEF 35%
Aldosterone receptor antagonists are recommended in patients
who have LVEF 40% following acute MI with symptoms of HF
Inappropriate use of aldosterone receptor antagonists may
be harmful
A combination of hydralazine and isosorbide dinitrate can be
useful in patients with HFrEF who cannot be given ACE
inhibitors or ARBs (African-Americans)

Pharmacological Therapy for Management

of Stage C HFrEF

Digoxin can be beneficial in patients with HFrEF (esp with

AF) unless CI
Patients with chronic HF and AF should receive chronic
anticoagulant therapy for cardioembolic stroke prophylaxis
Omega-3 PUFA supplementation is reasonable to use as
adjunctive therapy in HFrEF or HFpEF patients

Pharmacological Therapy CI for

Management of Stage C HFrEF

Drugs known to be potentially harmful and should be avoided or

withdrawn (e.g., most antiarrhythmic drugs, most CCBs
(except amlodipine), NSAIDs, TZDs or metformin)
Long-term infusion of positive inotropic drug is not
recommended and may be harmful except if recommended as
previously discussed

Management of Stage D

Mechanical circulatory support

Continuous intravenous positive inotropic therapy
Cardiac transplantation and hospital care