PATHOPHYSIOLOGY OF HEART

FAILURE

Lab of Cardiology and Vascular

Medicine
Faculty of Medicine
University of Brawijaya
Definition : Heart Failure
“The situation when the heart is incapable of
maintaining a cardiac output adequate to
accommodate metabolic requirements and the
venous return.“ E. Braunwald
“Pathophysiological state in which an
abnormality of cardiac function is responsible
for the failure of the heart to pump blood at a
rate commensurate with the requirements of
the metabolizing tissues.” Euro Heart J; 2001. 22: 1527-1560
DEFINITION OF HEART FAILURE.
Criteria 1 and 2 should be fulfilled in all cases

1. Symptoms of heart failure

(at rest or during exercise)
And
2. Objective evidence of cardiac dysfunction
(at rest)
And
(in cases where the diagnosis is in doubt)
3. Response to treatment directed towards
heart failure
Task Force Report. Guidelines for the diagnosis and treatment of chronic heart failure.
European Society of Cardiology.2001
 EPIDEMIOLOGY
Europe

The prevalence of symptomatic HF range from 0.4-2%.

10 million HF pts in 900 million total population
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1527-1560

USA

nearly 5 million HF pts.

± 500,000 pts are D/ HF for the 1st time each year.
Last 10 years  number of hospitalizations has increased.
Nearly 300,000 patients die of HF each year.
ACC/AHA Guidelines for the
Evaluation and Management of Chronic Heart Failure in the Adult 2001
DESCRIPTIVE TERMS in HEART FAILURE

 Acute vs Chronic Heart Failure

 Systolic vs Diastolic Heart Failure
 Right vs Left Heart Failure
 Mild , Moderate, Severe Heart Failure

Guidelines for the diagnosis and treatment of chronic heart failure

European Heart Journal (2001) 22, 1528
 New York Heart Association (NYHA)
Classification of Heart Failure
Class – I No limitation : ordinary physical exercise
does not cause undue fatigue, dyspnoea or
palpita-tions.

Class – II Slight limitation of physical activity :

comfor-table at rest but ordinary activity
results in fatigue, dyspnoea, or palpitation.

Class - III Marked limitation of physical activity :

comfor-table at rest but less than ordinary
activity results in symptoms.

Class - IV Unable to carry out any physical activity

with-out discomfort : symptoms of heart
failure are present even at rest with
increased discomfort with any physical
activity.
Guidelines for the diagnosis and treatment of chronic heart failure
European Heart Journal (2001) 22, 1531
(Adapted from Williams JF et al., Circulation. 1995; 92 : 2764-2784)
 ACC/AHA – A New Approach To The Classification of HF
Stage Descriptions Examples

A Patient who is at high risk for Hypertension; CAD; DM;

developing HF but has no rheumatic fever; cardiomyopathy.
structural disorder of the heart.

B Patient with a structural disorder LV hypertrophy or fibrosis;

of the heart but who has never LV dilatation; asymptomatic VHD;
developed symptoms of HF. MI.

C Patient with past or current Dyspnea or fatigue ec LV systolic

symptoms of HF associated with dysfunction; asymptomatic
underlying structural heart patients with HF.
disease.

D Patient with end-stage disease Frequently hospitalized pts ; pts

awaiting heart transplantation etc
ACC/AHA Guidelines for the
Evaluation and Management of Chronic Heart Failure in the Adult 2001
Stages in the evolution of HF and recommended therapy by stage

Stage A Stage B Stage C Stage D

Pts with : Pts with : Pts with : Pts who have
• Hypertension • Previous MI • Struct. HD marked symptoms
• CAD Struct. • LV systolic Develop Refract. at rest despite
• DM Heart dysfunction Symp.of • Shortness of Symp.of maximal medical
breath and fatigue, HF at rest therapy.
• Cardiotoxins Disease • Asymptomatic HF
reduce exercise
• FHx CM Valvular disease
tolerance

THERAPY THERAPY THERAPY THERAPY

• Treat Hypertension • All measures under • All measures under • All measures under
• Stop smoking stage A stage A stage A,B and C
• Treat lipid disorders • ACE inhibitor • Drugs for routine use: • Mechanical assist
• Encourage regular • Beta-blockers • diuretic device
exercise • ACE inhibitor • Heart transplantation
• Stop alcohol • Beta-blockers • Continuous IV
& drug use • digitalis inotrphic infusions for
• ACE inhibition palliation

ACC/AHA Guidelines for the

Evaluation and Management of Chronic Heart Failure in the Adult 2001
 EVOLUTION OF
CLINICAL STAGES
NORMAL
No symptoms
Normal exercise
Asymptomatic
Normal LV fxn LV Dysfunction
Compensated
No symptoms
Normal exercise
Abnormal LV fxnCHF
Decompensated
No symptoms
Exercise
CHF
Abnormal LV fxn
Refractory
Symptoms
Exercise
CHF
Abnormal LV fxn
Symptoms not controlled
with treatment
Evolution of the Concept of Heart Failure 1950 to
2000
1950 2000

Aetiology Hypertension CHD

Valvular heart dis Hypertension
Dilated CMP

Natural Course Slowly progressive Slowly

progressive (remodelling)
or
unpredictable and rapid
( coronary
event )
Understanding Hemodynamic model Neurohormonal
model

Common cause Pulmonary infection Sudden death

of death Pump failure

Arrhythmia Atrial Ventricular

Patophysiology of C H F
 g a b c d e f g a

AO
Aortic
Aortic closure
pressure
Ventricular
pressure
Cross- MO
over Atrial
pressure

M1 A2
Heart S4 T1 P2 S
sounds 3

Cardiologic
systole

a c
v

JVP
Opie (2001)

T P
P
ECG
Q S
0 800 msec

The Wiggers cycle

g
f

e iso
a b c d
iso
 PULMONARY VENOUS
PRESSURE

Input

Filling Emptying
Stroke
ED volume x EFeffective = volume
LV Distensibility Contractility x
Relaxation Afterload Heart
Left atrium Preload
Mitral valve rate
Structure
Pericardium
Diastolic function Systolic function

Output
ED: end diastolic
EF: ejection fraction
CARDIAC OUTPUT

Block diagram of left ventricular pump performance

(Little, 2001)
PRESSURE – VOLUME CURVE OF SYSTOLIC AND DIASTOLIC FAILURE

SYSTOLIC FAILURE DIASTOLIC FAILURE

Decreased
Normal diastolic
diastolic chamber
Normal
chamber
Left Ventricular Pressure

Left Ventricular Pressure

distensibility
distensibility

Left Ventricular Volume Left Ventricular Volume

(Zile & Brutsaert 2002)

 Abnormal Pericardial
relaxation restraint

Left ventricular pressure

A B
Increased Chamber
chamber stiffness dilation

C D
Left ventricular volume

Mechanisms that cause diastolic dysfunction. (Zile, 1990)

 DETERMINANTS OF
VENTRICULAR FUNCTION

CONTRACTILITY

PRELOAD AFTERLOAD

STROKE
VOLUME

- Synergistic LV contraction HEART

- LV wall integrity RATE
- Valvular competence

CARDIAC OUTPUT
Frank-Starling Law

Normal
Cardiac O utput Compensated

Normal C.O.

LVEDP: Left
Ventricular
End diastolic
CHF Pressure
CHF:chronic
Heart failure
CO: cardiac
output
LVEDP
 Ventricular Function Curve:
Frank-Starlings

Normal

SV

LVEDV Congestion
LVEDV: Left Ventricular End Diastolic Volume
SV: stroke volume
The Pathophysiology of Heart Failure

Hurst. The Heart. Diagnosis and Management of Heart Failure.10th ed. 688
 Pathophysiological Sequence of
CHF

Heart Failure

Inadequate Cardiac Output

(↓ ) O2 Delivery (rest and/or exercise)

Systemic Vasoconstriction

SAS (NE)) RAAS (A-II)

(↓) Flow to Skin, Gut,
and Renal Circulations
SAS: sympathetic autonomic system
RAAS: renin angiotensin aldosteron system; NE: nor epinephrine
Neurohormonal Activation

Activation of
RAS and ANS

Hurst. The Heart. Diagnosis and Management of Heart Failure.10th ed. 688
Frank-Starling Effect

Ventricular dilatation

W all stress

O2 consum ption Coronary

perfusion
 SNS
Preload Afterload
Renin release

Angiotensin II
Growth ALDO
factors
Vasoconstriction
Hypertrophy Fluid
Apoptosis accumulation
Collagen
deposition
SNS: sympathetic nervous system Myofibril
ALDO: aldosterone
necrosis
 Sympathetic nervous system up-regulation

Increased
Norepinephrine levels

Activation of the Decreased Direct

RAA system Renal blood Myocardial toxicity
flow
Myocyte dysfunction
Increased
Angiotensin II & Increased HR, PVR & Myocyte
Aldosteron arteriolar vasoconstriction necrosis

Increased myocardial Intracellular

Na & water
+
oxygen demand Ca2+ overload/
retention Energy depletion

Vasoconstriction Cardiac remodeling Apoptosis

HR: heart rate; PVR: peripheral Cesario et.al; Reviews in cardiovascular medicine, vol 3, no.1, 2002
vascular resistance
 Causes of Heart Failure

● Myocardial Damage or Disease

● Infarction
(Acute) / Ischemia
● Myocarditis
● Hypertrophic Cardiomyopathy

● Excess Load on Ventricle

● Volume/ Pressure Overload
● Resistance to Flow into Ventricle
● Cardiac Arrhythmias
 Primary Changes in CHF

Site of Backward Forward

Failure Failure Failure

Right Heart (↑) Systemic (↓) ejection

Failure Venous into
Pressure Pulmonary
Artery
Left Heart (↑) Pulmonary (↓) ejection
Failure Venous into aorta
Pressure
 MI-INDUCED HEART FAILURE
Myocardial Damage

Contractility

Pump Performance
( ↑↑) Systolic Work Load ( ↑↑) SAS Drive
Vasoconstriction

RAAS SYSTEM
FLUID RETENTION
MI: myocardial infarction; SAS:
sympathetic autonomic system
Diagnosis of C H F
IDENTIFICATIONS OF HF PATIENTS

 With a Syndrome of Decrease Exercise

Tolerance
 With a Syndrome of Fluid Retention
 With No Symptoms or Symptoms of
Another Cardiac or Non Cardiac
Disorder
(MI, Arrythmias, Pulmonary or
Systemic Thromboembolic Events)
 SYMPTOMS AND SIGN

 Breathlessness, Ankle Swelling, Fatique

→ Characteristic Symptoms

 Peripheral Oedema, JVP ↑, Hepatomegaly

→ Signs of Congestion of Systemic Veins

 S3 ⊕ , Pulmonary Rales ⊕ , Cardiac Murmur ⊕

 ECG
 A low Predictive Value
 LAH (left atrial hypertrophy) and LVH (left ventricular
hypertrophy) May Be Associated wit LV (left ventrcular)
Dysfunction
 Anterior Q-wave and LBBB a good predictors of EF ↓↓
 Detecting Arrhytmias as Causative of HF

CHEST X-RAY

 A Part of Initial Diagnosis of HF

→ Cardiomegaly, Pulmonary Congestion
 Relationship Between Radiological Signs and
Haemodynamic Findings may Depend on the
Duration
and Severity HF
 HAEMATOLOGY & BIOCHEMISTRY
 A Part of Routine Diagnostic
 Hb, Leucocyte, Platelets

 Electrolytes, Creatinine, Glucose, Hepatic Enzyme,

Urinalysis
 TSH (thyroid stimulating hormone), C-RP, Uric Acid

ECHOCARDIOGRAPHY
 The Preferred Methods
 Helpful in Determining the Aetiology
 Follow Up of Patients Heart Failure
 PULMONARY FUNCTIONS
 A Little Value in Diagnosis Heart Failure
 Usefull in Excluding Respiratory Diseases

EXERCISE TESTING

 Focused on Functional, Treatment Assessment

and
Prognostic
 STRESS ECHOCARDIOGRAPHY
 For Detecting Ischaemia
 Viability Study

NUCLEAR CARDIOLOGY

 Not Recommended as a Routine Use

CMR
( CARDIAC MAGNETIC RESONANCE IMAGING)

 Recommenmded if Other Imaging Techniques

not
Provided Diagnostic Answer
 INVASIVE INVESTIGATION

 Elucidating the Cause and Prognostic Informations

 Coronary Angiography :
in CAD’s (coronary artery disease) Patients
 Haemodynamic Monitoring :
To Assess Diagnostic and Treatment of HF
 Endomyocardial Biopsy :
in Patients with Unexplained HF
 NATRIURETIC PEPTIDES

 Cardiac Function ↓↓ (LV Function ↓↓) →

↑↑ Plasma Natriuretic Peptide
Concentration
(Diagnostic Blood Use for HF)
 Natriuretic Peptide ↑↑ :
Greatest Risk of CV Events
Natriuretic Peptide ↓↓ :
Improve Outcome in Patients with
Treatment
 Identify Pts. With Asymptomatic LV
Dysfunction (MI, CAD)
 ALGORITHM FOR THE DIAGNOSIS OF THE HF
(ESC, 2001)
Suspected Heart Failure
Because of symptoms and
signs
If Normal
Assess Presence of Cardiac Disease by ECG, Heart Failure
X-Ray or NatriureticPeptides (Where Unlikely
Available)

Tests Abnormal

Imaging by Echocardiography If Normal

(Nuclear Angiography or MRI Where Heart Failure
Available) Unlikely

Tests Abnormal

Assess Etiology, Degree, Precipitating

Factors and Type of Cardiac
Additional Diagnosis Tests
Dysfunction
Where Appropriate (e.g.
Coronary Angiography)
Choose Therapy
 Management Outline
Establish that the patient has HF.
Ascertain presenting features: pulmonary oedema, exertional breathlessness,
fatigue, peripheral oedema
Assess severity of symptoms
Determine aetiology of heart failure
Identify precipitating and exacerbating factors
Identify concomitant diseases
Estimate prognosis
Anticipate complications
Counsel patient and relatives
Choose appropriate management
Monitor progress and manage accordingly

Guidelines for the diagnosis and treatment of chronic heart failure

European Heart Journal (2001) 22, 1527-1560
 TREATMENT

Correction of aggravating factors

Pregnancy Endocarditis
Arrhythmias (AF) Obesity
Infections Hypertension
Hyperthyroidism Physical activity
Thromboembolism Dietary excess
MEDICATIONS
 Treatment options
Non-pharmacological management
General advice and measures
Exercise and exercise training

Pharmacological therapy
Angiotensin-converting enzyme (ACE) inhibitors
Diuretics
Beta-adrenoceptor antagonists
Aldosterone receptor antagonists
Angiotensin receptor antagonists
Cardiac glycosides
Vasodilator agents (nitrates/hydralazine)
Positive inotropic agents
Anticoagulation
Antiarrhythmic agents
Oxygen

Devices and surgery

Revascularization (catheter interventions and surgery), other forms of surgery
Pacemakers
Implantable cardioverter defibrillators (ICD)
Heart transplantation, ventricular assist devices, artificial heart
Ultrafiltration, haemodialysis
Guidelines for the diagnosis and treatment of chronic heart
failure
 DRUGS
HEMODYNAMIC EFFECTS
Normal
A
I
Stroke A+V
Volume
V
D CHF

Ventricular Filling Pressure

PHARMACOLOGIC THERAPY
Improved Decreased Prevention Neurohumoral
symptoms mortality of CHF Control
DIURETICS yes ? ? NO
DIGOXIN yes = minimal yes

INOTROPES yes mort. ? no

Vasodil.(Nitrates) yes yes ? no

ACEI yes YES yes YES
Other neurohormonal
control drugs
yes +/- ? YES
 TREATMENT

Normal
Asymptomatic
LV dysfunction
EF <40%
Symptomatic CHF
ACEI NYHA II Symptomatic CHF
Diuretics mild NYHA - III
Neurohormonal Symptomatic CHF
inhibitors Loop
NYHA - IV
Digoxin? Diuretics
Inotropes
Specialized therapy
Transplant
Secondary prevention
Modification of physical activity
Pharmacological therapy
Stages in the evolution of HF and recommended therapy by stage

Stage A Stage B Stage C Stage D

Pts with : Pts with : Pts with : Pts who have
• Hypertension • Previous MI • Struct. HD marked symptoms
• CAD Struct. • LV systolic Develop Refract. at rest despite
• DM Heart dysfunction Symp.of • Shortness of Symp.of maximal medical
breath and fatigue, HF at rest therapy.
• Cardiotoxins Disease • Asymptomatic HF
reduce exercise
• FHx CM Valvular disease
tolerance

THERAPY THERAPY THERAPY THERAPY

• Treat Hypertension • All measures under • All measures under • All measures under
• Stop smoking stage A stage A stage A,B and C
• Treat lipid disorders • ACE inhibitor • Drugs for routine use: • Mechanical assist
• Encourage regular • Beta-blockers • diuretic device
exercise • ACE inhibitor • Heart transplantation
• Stop alcohol • Beta-blockers • Continuous IV
& drug use • digitalis inotrphic infusions for
• ACE inhibition palliation

ACC/AHA Guidelines for the

Evaluation and Management of Chronic Heart Failure in the Adult 2001