Medicine II: Heart Failure Lecture

Manuel B. Zacarias, MD

Heart Failure Definition

v It is a complex clinical syndrome that can result from any
structural or functional cardiac disorder that impairs the
ability of the ventricle to fill with or eject blood
v Heart failure is preferred over CHF because not all
patients are volume overload at the time of initial
evaluation
v Clinical syndrome of HF may result from disorder of the
pericardium, myocardium or endocardium, or great
vessels but majority of patients have symptoms due to
impairment of LV function
v Cannot be assessed with precision accurate estimates
of prevalence, incidence, and prognosis are lacking
v Incidence average annual incidence per 1000

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Definition of Terms
v Cardiac output Quantity of blood pumped by the LV into the
aorta each minute (NV = 5L/min)
v Cardiac index CO/m2 (NV = 3.4L/min/m2; range of 2.8-4.2)
v Stroke volume End diastolic volume End systolic
volume
v Ejection fraction (SV/EDV) * 100 (NV = 60-75%)
Regulatory factors of myocardial contraction
v Preload
Load before ventricular contraction
Physiologically, the venous returne
The LVEDP
Wall stress at the end of diastole
v Afterload
The force resisting shortening of the myofibrils
v Contractility
Inotropic state
Accounts for alteration of performance induced by
hormonal and biochemical change
Increased when there is enhanced interaction between
calcium and contractile protein

Age
45-54
55-64
65-74
75-84
85-94

Men
2
4
9
18
39

Women
1
2
6
12
31

NYHA Functional Classification

Asymptomatic during daily usual
No limitation
I
activity
Symptoms during ordinary daily
II Slight limitation
activity
Symptoms noted during minimal
III Moderate
activity
limitation
IV Severe limitation Symptoms persist even at rest

Mechanisms of cardiac reserve

v Increased heart rate
Trained athletes = 200-230/minute
Normal young individuals = 170=180/min
Old, untrained, with heart disease = 120-140/min
v Increased stroke volume
EF = 60-75%
Normal
< 55%
Systolic dysfunction
< 40%
Depressed
< 20%
Severely depressed
v Increased oxygen extraction
v Redistribution of blood flow
Local autoregulation
Integrated response of the CNS
v Anaerobic metabolism 5-30% of energy requirement
v Cardiac dilation
v Cardiac hypertrophy

Cardiovascular Diagnosis
v Etiologic
v Anatomic
v Physiologic
v Functional Capacity (I-IV)
v Objective Assessment
No objective evidence of CVD
Objective evidence of minimal CVD
Objective evidence of moderately severe CVD
Objective evidence of severe CVD
Stages
Stage A
Stage B
Stage C
Stage D

High risk for developing HF but has no structural

disorder of the heart
Structural disorder of the heart but who has never
developed symptoms of HF
Past or current symptoms of HF associated with
underlying structural heart disease (symptomatic)
End-stage disease who requires specialized treatment
strategies (recurrent HF)

Examples
v Stage A
Systemic HPN
CAD
DM
Cardiotoxic drug therapy or alcohol abuse
Personal history of rheumatic fever
Family history of cardiomyopathy
v Stage B
LVH or fibrosis
LV dilatation or hypocontractility
Asymptomatic valvular heart disease
Previous myocardial infarction
v Stage C
Dyspnea or fatigue due to LV systolic dysfunction
Asymptomatic patients who are undergoing
treatment for prior symptoms of HF
v Stage D
End stage disease who requires specialized
treatment strategies such as mechanical circulatory
support, continuous inotropic infusions, cardiac
transplantation, or hospice care

Mechanisms of Cardiac Reserve

v 24% - Splanchnic
v 19% - Renal
v 21% - Skeletal
v 9% - Skin
v 10% - Other
v 13% - Cerebral, Coronary
Laplaces Law
v Wall stress = Pressure x Radius
2 x wall thickness
v As the pressure increases (ie. Due to aortic stenosis),
thickness of the LV increases in order to offset the pressure
overload; and wall stress remains normal)

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Acute MI
v 20-25% LV mass infarcted = LV dysfunction
v >40% LV mass infracted = cardiogenic shock

Examples are patients

Frequently hospitalized for HF or cannot be safely

discharged from the hospital

In the hospital awaiting heart transplantation

At home receiving continuous intravenous

support for symptom relief or being supported
with a mechanical circulatory assist device

In a hospice setting for management of HF

Systolic HF
v Impaired contractility leads to reduction in cardiac output.
This leads to fall in tissue perfusion, the activation of the
rennin-angiotensin and sympathetic nervous systems,
and eventually sodium and water retention

Heart failure
v Acute heart failure acute dyspnea with signs of pulmonary
congestion including pulmonary edema
v Cardiogenic shock low arterial pressure, oliguria, and cool
extremities
v Chronic HF punctuated by exacerbations
v Right HF syndromes presenting predominantly with
congestion of the systemic circulation
v Left HF syndromes presenting predominantly with
congestion of the pulmonary circulation
v Principal hallmark of HF
Systolic dysfunction: depressed LV EF (<40%)
Diastolic dysfunction: normal EF with impairment of one
ore more indices of ventricular filling
v Etiologies
Ischemic
Nonischemic
Unspecified
Specified
Idiopathic
Valvular
Hypertensive
Ethanol
Vital
Postpartum
Amyloidosis
Others

Frank-Starlings Law
v Intrinsic ability of the heart to adapt itself to changing
loads of inflowing blood
v Within physiologic limits, the heart pumps all the blood
that comes to it without allowing excessive damming of
blood in the veins
v Heterometric autoregulation
Cardiovascular continuum
Index Event
Acute MI
Gene mutation
Acute
inflammation
Onset of HPN
Valvular Heart
Disease
Others

Structural remodeling
and progression of
disease
Myocyte hypertrophy
Fibrosis, chamber
dilatation
Collagen shunt
dissolution
Cell drop out
(apoptosis)
Cell necrosis
Neuroendocrine
activation
Cytokine release
Increased wall
stretching
Chamber dysfunction

Clinical syndrome of
HF
Salt and water
retention
Congestion, edema
Low cardiac output
Diastolic dysfunction
Increasing
symptoms

HF as a progressive disorder
v LV dysfunction begins with some injury to the
myocardium and is usually a progressive process, even
in the absence of a new identifiable insult to the
myocardium
v The principal manifestation of such progression is a
process known as remodeling, which occurs in
association with homeostatic attempts to decrease wall
stress through increases in wall thickness, which
ultimately results in a change in the geometry of the LV
such that the chamber dilates, hypertrophies, and
becomes more spherical
v Cardiac remodeling
Generally precedes the development of symptoms,
occasionally by months or even years
Continues after the appearance of symptoms
May contribute importantly to worsening of
symptoms despite treatment
v Factors that contribute to LV remodeling
Neurohormones and cytokines
Increased LV volume and pressure
Myocardial cell elongation
Replacement and reactive collaged deposition (ie.
Increased collagen turnover)
Myocyte slippage secondary to dissolution of
collagen struts
Apoptosis
Necrosis
Myocardial infarct expansion
Dilation and reshaping of the LV

Ischemic cascade
v Coronary artery occlusion
v Diastolic abnormalities
v Systolic abnormalities
v Perfusion defects
v Hemodynamic abnormalities
v ECG changes
v Angina

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Vascular Pathophysiology of HF

Consequences of neurohormonal stimulation in HF

Consequence of Neurohormonal Stimulation

Pathophysiology

Terminal events in HF
v Systemic organ failure
v Pulmonary/ cerebral embolus
v Lethal arrhythmias
Neuroendocrine factors known to be increased in HF
Endothelin
Norepinephrine
Beta-endorphins
Epinephrine
Calcitonin gene-related peptide
Renin activity
Growth hormone
Angiotensin II
Cortisol
Aldosterone
TNF alpha
Arginine vasopressin
Neurokinin A
Neuropeptide Y
Substance P
VIP
Adrenomedullin
Prostaglandins
Brain natriuretic peptide
Atrial natriuretic factor
Assessment of patients with HF
v History and PE
v Diagnostic Studies
Laboratory tests
Electrocardiography
CXR
Exercise testing
ECG
Radionucleotide imaging
Cardiac catheterization
Endomyocardial biopsy

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Cardinal Manifestations/ Symptoms of HF

v Dyspnea
Any abnormally uncomfortable awareness of breathing
Usually exertional
May develop at rest
Relieved by rest, diuretics and digitalis
May be accompanied by wheezing
v Fatigue
Deconditioning inactivity or prolonged bed rest; loss of
capability for effective redistribution of systemic blood
flow
v Weakness
v PND
Onset is 2-5 hours after sleeping
Relief 15-30 minutes after sitting/standing
Accompanied by cough, wheezing, sweating, anxiety
v Orthopnea
Dyspnea on recumbent position, relieved by sitting or
standing
v Dyspnea on exertion
v Decreased exercise tolerance
Mechanisms responsible for exercise intolerance in
patients with chronic HF have not been clearly defined
Very low EF may be asymptomatic
Preserved EF may have severe disability
The cause of this discordance is not well understood
v Unexplained confusion, altered mental status or fatigue in an
elderly patient
v Abdominal symptoms (eg. Nausea, abdominal pain, bloating,
loss of appetite)
PE findings in HF
v Elevated JVP or positive abdominal jugular reflex
v A third heart sound
v The third heart sound
v Murmurs
Displaced AB
v Rales that do not disappear with cough
v Peripheral edema
v Narrow pulse pressure
Right Heart Failure
Cyanosis
Increased JVP
Hepatomegaly
Ascites
Dependent edema
CXR: marked RV dilatation

Left Heart Failure

Dyspnea
Orthopnea
CXR: Pulmonary congestion

Dependent edema
Facial edema
Ascites
Hypoalbuminemia
Proteinuria

Cardiac
Severe
Absent

Hepatic
Moderate
Absent

Absent/
mild
Absent

Severe
Moderate/
Mild
Absent/
trace

Absent/
trace

Severe
Severe

CHF Diagnostic Criteria (Framingham)

Requires 1 Major and 2 Minor Criteria
Major
PND
Neck vein distention
Rales
Cardiomegaly
Acute pulmonary edema
S3 gallop
Venous pressure >16cm H20
(+) Hepatojugular reflux

Minor
Extremity edema
Night cough
Dyspnea on exertion
Hepatomegaly
Pleural effusion
Reduced vital capacity
Tachycardia (>120/min)

Weight loss >4.5 kg over 5 days treatment

Laboratory Tests
Test
recommendation
CBC

Urinalysis

Finding
Anemia

Serum creatinine

Proteinuria
RBCs or cellular
casts
Elevated failure

Serum albumin

Decreased

T4and TSH (only if

atrial fibrillation, with
thyroid disease or
age > 65)
Electrocardiogram

Abnormal T4 or TSH

Acute ST-T wave

changes
Atrial fibrillation,
other
tachyarrhythmia
Bradyarrhythmia
Previous MI (eg. Q
wave) left ventricular
performance
Low voltage
LVH

PE findings
v CAP assessment
Normal: brisk, tapping
Sustained: plateau, dome-shaped, rising movement
v Sustained AB
LV outflow obstruction
Systemic HPN
Depressed systolic function
v Hepatojugular/ abdominojugular refex
Firm, sustained upper abdominal pressure
Patient breathing quietly
Normal transient 1cm JVP increase
HF: sustained elevation of JVP
v Cardiovascular edema
History of HPN/ heart disease
Primarily complaining of SOB
Peripheral

Renal
Mild
Severe/
moderate
Absent/ mild

Suspected
HF due to or
aggravated by
decreased O2carrying capacity
Nephritic syndrome
Glomerulonephritis
Volume overload
due to renal
dysfunction
Increased
extravascular
volume due to
hypoalbuminemia
HF due to or
aggravated by hypo/
hyperthyroidism
Myocardial ischemia
Thyroid disease or
HF due to rapid
ventricular rate
HF due to low heart
rate
HF due to reduced
contractile tissue
Pericardial effusion
Diastolic dysfunction

Chest X-ray
v Cardiomegaly
v Hilar vascular congestion
v Bronchial cuffing
v Cephalization of vessels
v Kinsley lines
Echocardiography
v Advantages
Permits concomitant assessment of valvular
disease, LVH, and LA size
Less expensive than radionucleotide
ventriculography in most areas
Able to detect pericardial effusion and ventricular
thrombus
More generally available

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v Pharmacologic Therapy
Improvement of symptoms

v Disadvantages
Difficult to perform in patients with lung disease
Usually only semiquantitative estimate of ejection
fraction provided
Technically inadequate in up to 18% of patients under
optimal circumstances

Digoxin
Diuretics
Beta blockers
ACEI
ARB

Prolongation of patient survival

Radionucleotide ventriculogram
v Advantages
More precise and reliable measurement of EF
Better assessment of right ventricular function
v Disadvantages
Requires venipuncture and radiation exposure
Limited assessment of valvular heart disease and LVH

Vascular Pathophysiology
v Vasoconstricting systems
Atrial Natriuretic Peptide (ANP)
Released from the atria (sometimes the ventricle) in
response to volume expansion (stretch)
ANP ANP receptor guanylate cyclase cGMP
Inhibit RAS and inhibit sympathetic activity
vasodilator
Promotes sodium excretion natriuresis and
diuresis
Brain Natriuretic Peptide (BNP)
Released from the brain (and ventricle) in response to
volume expansion (stretch)
Diagnosis of HF
Screening for diastolic HF
Predictor of HF
Prognosis of HF
Guide to therapy of HF
Prognosis in ACS
BNP > 100pg/mL = HF
Sensitivity 90%
Specificity - 76%
Predictive accuracy of 83%
General Principles of Treatment
v General Principles of Treatment
Correction of systemic factors
Lifestyle modification
Review drugs that my contribute to HF
Treatment of the cause of HF
Pharmacologic therapy

ACEI
ARB
Beta blockers
Spirinolactone/ eplerenone

Diuretics mainly to relieve symptoms

ACEI given with or after optimization of diuretic
therapy
Beta-blockers initiated after stabilization with ACEI.
Start with low dose
Digoxin to those who continue to have symptoms
despite above regimen, and for rate control of AF
with RVR
ARB added to above regimen for Class II and III,
spirinolactone and eplerenone for Class IV patients
Hydralazine and nitrates may be an alternative to
ARB in black patients
Pharmacologic therapy
v Diuretics
Helps reduce the amount of water in the body
Adverse effects of loop diuretics (similar to
thiazides in may respects)
Hypokalemia, metabolic alkalosis,
hypercholesteronemia, hyperuricemia, hyperglycemia,
hyponatremia
Dehydration and postural hypotension
Hypocalcemia (in contrast to thiazides)
Hypersensitivity
Ototoxicity (if given by rapid IV bolus)

v Deleterious effects of aldosterone

Vascular inflammation and injury
Potassium and magnesium loss
Central hypertensive effects
Endothelial dysfunction
Ventricular arrhythmias
Sodium retention
Catecholamine potentiation
Myocardial fibrosis
Prothrombotic effects

v Potassium sparing diuretics

Eg. Spirinolactone, eplerenone
Compete with aldosterone for the mineralocorticoid
receptor
Prolong survival in selected patients
Eplerenone more specific for mineralocorticoid
receptor than spirinolactone, less side effects
Mild diuretics
To improve survival in patients with recent or
current NYHA class IV symptoms (RALES trial
criteria)
To improve survival in selected patients with LV
dysfunction after an acute MI
To assist management of diuretics induced
hypokalemia (plasma potassium < 3.8 mEq/L) in
patients with mild to moderate HF
The ACC/AHA guidelines recommended the use of
low doses of spirinolactone (25-50 mEq/day) in
patients with recent or current NYHA Class IV HF,
a serum creatinine concentration < 2.5 mg/dL and
a serum potassium < 5 mEq/L
v Vasodilators ACEI, ARB, Sodium nitroprusside
v ACE Inhibitor
All patients with asymptomatic or symptomatic LV
dysfunction should be started on an ACEI

Relief of symptoms
Slow progression
Improve survival

Specialized therapy for refractory HF

v Systemic Factors causing HF
Inappropriate medications
Superimposed infection
Anemia
Uncontrolled diabetes
Thyroid function
Electrolyte disorders
Pregnancy

v Lifestyle modification
Stop smoking
Limit alcohol intake
Decrease salt intake : 2 to 3g sodium/day
Restrict water intake
Daily weight monitoring
Cardiac rehab, program for stable patients

v Treatment of the cause

HPN
Coronary heart disease medications,
revascularization
Valvular heart disease surgery
Cardiomyopathy - specific
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v ARBs

Begin therapy with low doses (eg. 2.5 mg of enalapril

BID or 6.25 mg of captopril TID) then gradually increase
to maintenance dose of 10mg BID of enalapril, 5 mg
TID of captopril, or up to 4mg.day of lisinopril or
quinapril unless side effects occur

ARBs for the treatment of HF appear to be as effective

as, or possibly slightly less effective than ACEIs when
compared directly
They should not be used in preference to ACEIs
v Beta blockers
Carvedilol, metoprolol and bisoprolol improve overall
and event free survival in patient with NYHA class II to
III HF and probably in class IV HF
Beta blocker with intrinsic sympathomimetic activity
(such as pinolol and acebutolol) should be avoided
Relative contraindications for beta blockers in patients
with HF

Summary of Management
v Stage A High risk for developing HF but has no
structural disorder of the heart
Treat HPN
Smoking cessation
Treat dyslipidemia
Discourage alcohol and illicit drug use
ACEI in appropriate patients
v Stage B Structural disorder of the heart but who has
never developed symptoms of HF
All measures under stage A
ACEI in appropriate patients
Beta blockers in appropriate patients
v Stage C Past or current symptoms of HF associated
with underlying structural heart disease
All measures under stage A
Drugs for routine use: diuretics, ACEI, beta
blockers, digitalis
Salt restriction
v Stage D End stage disease who requires specialized
treatment strategies
All measures under stages A, B, C
Mechanical assist device
Heart transplant
Continuous IV inotropic infusion
Hospice care

HR < 60
Systolic arterial pressure <100 mmHg
PR interval > 0.24 sec
Second or third degree AV block
Severe COPD
History of asthma
Severe peripheral vascular disease

Beta blockers may lead to an increase in symptoms for

4 to 10 weeks before any improvement is noted.
Therapy should be begun as very low doses and the
dose doubled at regular intervals (eg. Every 2 to 3
weeks) until the target dose is reached or symptoms
become limiting
v Digoxin
Given to patients with HF and systolic dysfunction to
control symptoms (such as fatigue, dyspnea, and
exercise intolerance) and, in patients with atrial
fibrillation, to control the ventricular rate
v CACB
There is no direct role for these drugs in the
management of HF. However, amlodipine and
felodipine appear to be safe in patients with HF and can
be used if treatment with a CACB is necessary for
another indication, such as angina or HPN
Felodipine does not affect mortality in HF
v Indications for hospitalization

Diagnostic Criteria for Diastolic Heart Failure

v Signs and symptoms of CHF
Exertional dyspnea
Orthopnea
Gallop sounds
Lung crepitations
Pulmonary edema
v AND normal or mildly reduced LV systolic function
v AND evidence of abnormal LV relaxation, filling,
distensibility, and diastolic stiffness

Hypotensive with organ hypoperfusion

Profound fluid retention states
Substantive renal or hepativ insufficiency
Hemodynamic instability requiring IV inotropes
Dysrrhythmias requiring IV antiarrhythmics
Decompensated HF with refractory angina
Complication of post cardiac transplantation
Elevated CPK and CPK-MB and/or ECG with ischemia/ injury
or new necrosis

Treatment of Diastolic Dysfunction

Goals
Reduce preload
Maintain atrial
contraction
Enhance ventricular
emptying
Regression of
hypertrophy
Control heart rate

Specialized Therapy for Refractory HF

v Intravenous Inotropes and vasodilators
IV Inotropes
Norepinephrine
Epinephrine
Isoproterenol
Dopamine
Dobutamine
Amrinone
Milrinone

v
v
v
v

IV vasodilators
Nitroprusside
Nitroglycerine

Prevent and treat

ischemia
Improve myocardial
relaxation

Hemodynamic monitoring
Pacemakers
Hemofiltration
Mechanical circulatory support
Criteria for LV assist device implantation

v Surgery
v Cardiac Transplantation
Treatment of Associated Conditions
v Supraventricular arrhythmias
Rate control
Restoration of sinus rhythm
v Ventricular arrhythmias
v Anticoagulation
v Anemia

Methods
Venodilators, Diuretics, Morphine,
Tourniquet, Salt Restriction
Cardioversion of AF, Atrial antiarrhythmics,
Avoid atrial distension
Anti-HPN therapy
Anti-HPN therapy
Exercise limitation, beta blocker,
cardioversion of AF, rate control of AF
Anti-HPN therapy, Control HR, Beta
blocker, CACB, nitrates, revascularization
CACB? Beta blocker? ACEI?

Prognosis
v Less than 50% of patients will survive for 5 years after
the onset of heart failure
v Sudden cardiac death is responsible for approximately
1/3 of deaths in patients with heart failure

Active heart transplant candidate

On maximal inotropic support, with or without intra
aortic balloon pump
Systolic pressure < 80mmHg with either: cardiac index
<2L/m2 or PCWP < mmHg
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