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M. Saifur Rohman, MD, PhD
Cardiologist
Medical Faculty, Brawijaya University
MSR, May4 2010
Definition of HF

A syndrome associated with inadequate
performance of the heart.

Leading to neurohormonal and circulatory
abnormalities
Adam KF et al. HFSA 2006 comprehensive heart failure guideline J Card Fail 2006; 12: e1-e122
Epidemiology

Heart failure is a major and growing cause of cardiovascular
morbidity and mortality throughout the world

Approximately 5 million patients in USA have HF, and over
550 000 patients are diagnosed with HF for the first time
each year.

HF is the primary reason for 12 to 15 million office visits
and 6.5 million hospital days each year.
ESC Guideline for Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Causes of HF
• CAD
• Hypertension
• Valve disease (RHD, endocarditis)
• Arrhythmias
• Cardiomyopathy
• Congenital heart disease
• Pericardial Effusion
Systolic vs. Diastolic HF

Heart failure is a major and growing cause of cardiovascular
morbidity and mortality throughout the world

Previously, it had often been assumed that most heart failure
patients have underlying systolic dysfunction, which is
responsible for their clinical presentation

It has become increasingly apparent over the last decade that
many heart failure patients have a normal or nearly normal
ejection fraction described as heart failure with preserved
systolic function or preserved ejection fraction

HF-PEF affects primarily older patients, especially women;
hypertension is the primary underlying condition, with CAD and
prior MI being relatively infrequent
Hogg K, Swedberg K, McMurray J. J Am Coll Cardiol 2004; 43:317-327.
Systolic vs. Diastolic HF

Heart failure 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
Diastolic Heart Failure/
HF-PEF
Systolic Heart Failure
ACC-AHA guidelines 2001
Pathological/Echocardiographic Differences in
LV Thickness with Different Forms of HF
Systolic heart
failure
Normal
Heart failure with
preserved systolic
function
Aurigemma GP et al. Circulation. 2006;113:296-304.
Systolic HF vs HF-PEF: Signs and Symptoms
Parameters
Systolic
HF-PSF
History
• Coronary artery disease
• Hypertension
• Diabetes
• Valvular heart disease
• Paroxysmal dyspnea
+++
++
++
++++
++
++
+ ++
++++ +
++
—
+++
Physical Examination
• Cardiomegaly
• Soft heart sounds
• S3 gallop
• S4 gallop
• Hypertension
• Mitral regurgitation
• Rales
• Edema
• Jugular venous distention
+++
++++
+++
+
++
+++
++
+++
+++
+
+
+
++ +
+ ++
+ ++
++++ +
+
++
+
+
+++
+++
+
+++
Chest Roentgenogram (X-ray)
• Cardiomegaly
• Pulmonary congestion
Givertz MM et al. In: Braunwald E, Zipes DP, Libby P, eds. Heart Disease, A Textbook of Cardiovascular Medicine. 7th edition.
CHF vs. AHF

Current management of acute coronary syndrome
has resulted in an improved survival after acute
myocardial infarction.

This fact has created a rapid growth in the number
of patients currently living with chronic heart
failure.

Decompensation of preexisting chronic heart
failure may cause acute heart failure (AHF).
Eur Heart J 2005;26:384-416
Definition of Acute Heart Failure
• AHF is defined as the rapid onset of
symptoms and signs, secondary to abnormal
cardiac function
• Cardiac dysfunction can be related to
systolic or diastolic, to abnormalities in
cardiac rhythm or to preload and afterload
mismatch
• It is often life threatening and requires
urgent treatment
ESC guideline for Acute Heart Failure, 2005
Cause of Acute Heart Failure

Acute coronary syndrome, hypertensive crisis and
other cardiac or non cardiac also precipitate an AHF.

CAD contributes to 60-70 % in elderly
Cardiomyopathy, CHD, arrhythmia, myocarditis and
valve diseases found in young


AHF therefore has significantly become the single
most costly medical syndrome in emergency.
Eur Heart J 2005;26:384-416
Cause of Acute Heart Failure
Ischemic heart Disease
Acute Coronary Syndromes
Mechanical complication of acute MI
RV infarction
Valvular
Valve stenosis
Valve regurgitation
Endocarditis
Aortic disection
Myopathies
Postpartum cardiomyopathy
Acute myocarditis
Hypertension/arrhythmia
Hypertension
Arrhythmia
Circulatory failure
Septicemia
Thyrotoxicosis
Shunts
Tamponade
Pulmonary embolism
Decompensation
of preexisting CHF
Lack of adherence
Volume overload
Infection; pneumonia
Cerebrovascular insult
Surgery
Renal dysfunction
Asthma, COPD
Drug abuse
Alcohol abuse
ESC Guideline for
Diagnosis and Treatment Acute
and Chronic Heart Failure , 2008
Classification of AHF
• Patient with AHF present with six distinct
clinical conditions :
Worsening decompensated of chronic HF
Pulmonary edema
Cardiogenic shock
Hypertensive HF
Isolated right HF
ACS and HF
ESC Guideline for
Diagnosis and Treatment Acute
and Chronic Heart Failure , 2008
Mortality of AHF



In Hospital mortality ( 60 days) : 9.6%
Rehospitalization and mortality : 32,5%
1 year mortality : 30%.
Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.
Diagnosis of Heart Failure



Symptoms typical of HF
Sign typical of HF
Objective evidence of a structural or functional
abnormality of the heart at rest
ESC Guideline for
Diagnosis and Treatment Acute
and Chronic Heart Failure , 2008
Framingham Heart Failure Study
Criteria
Major
 Acute pulmonary edema
 PND or orthopnea
 Crackles
 S3 gallop
 HJR/Increased JVP
 Cardiomegaly
 Wt loss >4.5 kg 5d into
Rx
Minor
 Night cough
 Tachycardia >120
 Pleural effusion
 Hepatomegaly
 Ankle edema
 Vital capacity decrease
>1/3 from max
*Two major or one major and two minor*
NYHA Functional Heart Class
NYHA I: no symptoms on ordinary activity
NYHA II: symptoms on ordinary exertion
NYHA III: symptoms on less-than ordinary
exertion
NYHA IV: symptoms at rest
At Risk for CHF (ACC/AHA)
Stage A
Stage B
At high risk of HF but without
structural heart disease or HF
symptoms:
Structural Heart Disease but
without signs or symptoms
of HF:
Pts. with HTN, CHD,
diabetes,obesity, metabolic
syndrome
OR
Pts. using cardiotoxins or
family hx. cardiomyopathy
Pts. with previous MI, LV
remodeling including LVH,
and low LVEF
OR
asymptomatic valvular
disease
Heart Failure (ACC/AHA)
Stage C
Stage D
Structural heart disease
with prior or current HF:
Refractory HF requiring
specialized intervention:
Pts. with known structural
heart disease
AND
SOB, fatigue,
reduced exercise tolerance
Pts. with marked symptoms at
rest despite maximal
medical therapy
Recurrent hospitalization
Unsafe hospital discharge
Common Clinical Manifestation of HF
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Common ECG abnormalities in HF
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Common X-ray abnormalities in HF
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Common lab. abnormalities in HF
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Common echo. abnormalities in HF
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Diagnosis of HF
Clinical examination,
ECG,
Xray,
Echocardiography
Natriuretic peptides
BNP<100 pg/ml
NT-proBN P<400 pg/mL
BNP 100-400 pg/ml
NT-proBNP 400-2000 pg/ml
BNP>400 pg/ml
NT-proBNP>2000 pg/ml
Uncertain diagnosis
Chronic HF unlikely
Chronic HF likely
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Assessment of Haemodynamic Profile
Low perfusion at rest
Congestion at rest
No
No
Yes
A
B
Warm & dry
Warm & wet
Cold & dry
Cold & Wet
Yes
L
Sign of congestion:
Orthopnea,elevated JVP,edema,
pulsatile hepatomegaly, ascites,
rales,louder S3,P2 radiation left
ward, abdomino-jugular reflex,
valsava square wave
C
Sign of low perfusion:
Narrow pulse pressure,cool ex
tremities,sleepy, suspect from
ACEI hypotension, low Na, renal
worsening
European Heart Journal of Heart Failure,2005; 7:323-331
Treatment HF





Bed rest
Fluid management
Drug
Device
Stem cell
ERAS OF HEART FAILURE MANAGEMENT
Non-pharmacological
• Bed rest
Pharmacological
• Gene therapies
• Digitalis
• Inactivity
• Fluid restriction
• (Digitalis, diuretics)
pre -1980’s
Cellular/genetic
1980’s
• Diuretics
• Cell implantation/
regeneration
• Neurohormonal interventions
• Xenotransplantation
1990’s
2000’s
2020’s ⇒
Pharmacological
Device
• Digitalis
• CRT
• Diuretics
• ICDs
• Vasodilators
• LVADs
• Inotropes
• Others?
Heart Failure Updates, 2003
THE DONKEY ANALOGY
Ventricular dysfunction limits a patient's ability to perform
the routine activities of daily living…
HEART FAILURE
TREATMENT OPTION FOR HF
INOTROPIC
Like the carrot placed in front of the donkey
ACEI AND DIURETICS
Reduce the number of sacks on the wagon
ß-BLOKERS
Limit the donkey’s speed, thus saving energy
Patient Treatment Selection
Dry
Warm
Wet
A
Diuretic
Vasodilator
B
Inotropic drugs :
Dobutamine
Milrinone
Levosimendan
Cold
L
C
Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7–S12.
Treatment Algorithm in AHF
Acute Heart Failure
Immediate symtomatic treatment
Patient distress or in pain
Yes
Analgesia, sedation
Pulmonary congestion
Yes
Medical therapy
Diuretic/vasodilator
Arterial Oxygen saturation < 95%
Yes
Increase FiO2,
consider CPAP, NIV
Mechanical ventilation
Normal heart rate and rhythm
No
Pacing, antiarrhythmias,
electroversion
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
Treatment Algorithm in AHF
ESC Guideline for
Acute Heart Failure, 2005
Treatment Algorithm in AHF
ESC Guideline for
Acute Heart Failure, 2005
AHF with Systolic Dysfunction
Oxygen/CPAP
Furosemide + vasodilator
Clinical evaluation (leading to mechanistic therapy)
SBP > 100 mmHg
SBP 85-100 mmHg
SBP <85 mmHg
Vasodilator
(NTG, nitroprusside, BNP)
Vasodilator and/or
Inotropic (dobutamin
PDEI or Levosimendan)
Volume loading ?
Inotrope and/or
Dopamin > 5mcg/kg/mnt
And/or norepinephrine
Good response
Oral therapy
Furosemide, ACE-I
No respon :
Reconsider mechanistic
therapy
Inotropic agent
Eur Heart J 2005;26:384-416
Treatment of HF
ESC Guideline for
Diagnosis and Treatment Acute and Chronic Heart Failure , 2008
HF Prevention




Early diagnosis and prompt treatment of
MI = ACS treatment
Treat Hypertension
Treat and prevent DM to prevent
Cardiomyopathy DM
Early diagnosis of Myocarditis to prevent
cardiomyoptahy
From MI to HF


Early diagnosis and vascularization prevent
HF
Delay and inadequate treatment 
iireversible cardiomyocyte loss
Myocardial infarction leads
to heart failure

Obstruction of coronary arteries leads to
myocardial infarction (heart attack) with the
associated death of cardiomyocytes

Regenerative capacity ? Not adequately
compensate

Overloads the surviving myocardium and
eventually leads to heart failure
Segers VF, Lee RT. Nature 2008; 451: 937-942.
Terminal differentiation of
cardiomyocytes

Cardiac myocytes rapidly proliferate during fetal
life but exit the cell cycle soon after birth in
mammals1

The vast majority of adult cardiac myocytes the
predominant form of growth postnatally is an
increase in cell size (hypertrophy)2

This limits the ability to restore function after any
significant injury2
1. Ahuja P, et al. Physiol Rev 2007; 87: 521–544.
2. Segers VF, Lee RT. Nature 2008; 451: 937-942.
Problem with Infarcted Heart

Current medical therapies of heart failure only
delay progression of the disease

The only standard therapy for cardiomyocyte loss
is cardiac transplantation

New discoveries on the regenerative potential of
stem cells have transformed experimental research
and led to an explosion in clinical investigation

Results ?
Segers VF, Lee RT. Nature 2008; 451: 937-942.
HF Prevention




Treat Hypertension
Early diagnosis and prompt treatment of
MI
Treat and prevent DM to prevent
Cardiomyopathy DM
Early diagnosis of Myocarditis to prevent
cardiomyoptahy
The Cardiovascular Continuum
Coronary
thrombosis
Myocardial
infarction
Myocardial
ischaemia
X
Prevention II
Sudden Death
Arrhythmia &
loss of muscle
Remodelling
Ventricular
dilatation
CAD
Atherosclerosis
LVH
X
Prevention I
Risk factors
Hypertension, smoking, cholesterol, diabetes
Dzau V. Braunwald E, Am Heart J. 1991
Congestive
heart failure
Death
Classification of Blood Pressure
ESC-ESH 2007
Optimal
: <120 and < 80
Normal
: 120-129 and/or 80 - 84
High Normal : 130-139 and/or 85-89
Grade 1 : 140-159 and/or 90-99
Grade 2 : 160-179 and/or 100-109
Grade 3 : > 180 and/or > 110
JNC VII committee, JAMA 2003: 289;2560-2572
JNC-VII
Normal
Pre-hypertension
Stage 1
Stage 2
H
Y
P
E
R
T
E
N
S
I
O
N
Epidemiology of Hypertension

90% lifetime risk of developing hypertension in
people normotensive at age 55

People with lower educational and income levels
tend to higher levels of blood pressure
American Heart Association Heart Disease and Stroke statistic 2006 Update, Texas, AHA2006
Prevalence of Hypertension
Prevalence of hypertension in different regions of the
world: Actual figures for 2000 - predicted for 2025
Rate of hypertension
%
50
Men
Women
40
2000
30
20
10
116.2
123.3
40.8
52.5
60.4
57.8
60.0
54.3
35.9
37.9
98.5
83.1
38.4
33.0
38.2
41.6
0
± 2x
± 2x
50
40
number of
people with
HT (millions)
2025
30
20
10
0
147.9
161.8
44.0
59.7
107.3
106.2
102.1
98.5
72.2
80.4
151.7
147.5
67.3
62.1
73.6
77.1
number of
people with
HT (millions)
Kearney et al Lancet 2005
Hypertension is Not Adequately Treated
Off all the USA people with high blood pressure:



11% are not on treatment regimen
25% are not on adequate treatment
34% are on adequate treatment
American Heart Association Heart Disease and Stroke statistic 2006 Update, Texas, AHA2006
Hypertension Prevalence and Treatment
Patients on Therapy
55
50
100
90
45
80
40
%
US
Canada
Italy
Sweden
England
Spain
Finland
Germany
70
35
%
30
60
50
25
40
20
30
15
20
10
10
5
0
0
Country
Wolf-Maier K et al. JAMA. 2003;289:2363-2369.
Country
Controlled Hypertension
< 140/90 mmHg
USA
27
England
Canada
16
< 160/95 mmHg
Finland
Spain
20.5
20
France
Germany
24
22.5
6
Scotland
17.5
Australia
19
India
9
> 65 years
USA: JNC VI. Arch Intern Med 1997
Marques-Vidal P et al. J Hum Hypertens 1997
Canada: Joffres et al. Am J Hypertens 1997
Adapted from G. Mancia / L. Ruilope
England: Colhoun et al. J Hypertens 1998
France: Chamontin et al. Am J Hypertens 1998
Uncontrolled BP in Outpatient Clinic
Three hundred third teen patients were randomly chosen among patients
with or without known hypertension visited to Harapan Kita out patient
HTN
65.8%
Non HTN
34.2%
Hypertensinwas diagnosed in 65.8 % patients visiting to
outpatient clinic Harapan Kita Cardiovascular Center
Saifur Rohman et al. unpublished data, 2008
Controlled
39.3%
Uncontrolled
60.7%
Among hypertensive patients only 39.3% reached blood
pressure target of SBP<140 and DBP<90 mmHg
Blood Pressure Target Achievement in
dr. Saiful Anwar Hospital
,0,0
Control
led
47.1%
uncontr
olled
52.9%
2011
2012
Optimized antihypertensive drug and Education for Compliance
Mifetika Lukitasari et al. ASMIHA abstract book, 2012
Saifur Rohman et al. Asean Heart Journal 2011;19:20-23
Mifetika Lukitasari et al. INASH abstract book, 2013
BP in AMI pts on EDAdmission : Awareness
SBP<140 and DBP<90
Number of Patient
SBP≥140 and DBP≥90
Unaware of HT
Aware of HT
Saifur Rohman et al. unpublished data, 2010
Consequences Structural Changes
in Hypertension
Loss of buffering
Function
Increased blood pressure
Structural changes in
compliance arteries
Transmits
 Systolic pressure
Wave to small arteries
 Compliance
 Shear stress on
Artery wall
Endothelial
dysfunction
 Load on heart
Perpetuation of
Hypertension
Left Ventricular
Hypertrophy
Dzau VJ. Hypertension. 2001;37:1047-1052
Predisposes of
Atherosclerosis
The Progression from Hypertension
to Heart Failure
LVH
Diastolic
dysfunction
CHF
Hypertension
Systolic
dysfunction
MI
LV
Normal LV
Structure & Function remodeling
Subclinical
Overt
LV dysfunction Heart Failure
Time
(decades)
Vasan RS, Levy D. 1996. Arch Intern Med 156 : 1759-1796
Time
(months)
Death
The Importance of HTN in
Development of HF

Hypertension (HTN) is present in 91% of patients
who develop CHF, tripling the risk of normotensive

HTN is a common risk factor of HF, treatable, and
often under-treated

Hypertension remains the major preventable factor
Vasan RS, Levy D. 1996. Arch Intern Med 156 : 1759-1796
Cumulative Incidence of Heart failure in
Normotensive and Hypertensive Patients
20
Stage 2 hypertension
15
CHF
Cumulative
Incidence 10
(%)
Stage 1 hypertension
5
Normal BP
0
5
10
Years From Baseline Exam
Lenfant C, Roccella EJ. J Hypertens Suppl. 1999;17:S3-S7.
Data from Levy D et al. JAMA. 1996;275:1557-1562.
15
Heart failure development:
Population-attributable risk
Prevalence Attributable
(%)
risk (%)
60
39
62
59
10
34
3
13
11
5
9
6
8
6
5
12
4
4
3
5
5
7
8
8
Hypertension
MI
Angina pectoris
Diabetes
LVH
Valvular disease
male
female
1
1.5
3.0 4.5
Hazard Ratio
7.5
Levy et al JAMA 1996
Annual acute management costs of
inadequately treated hypertension
Cost model based on 29 million adults in 5 EU countries
(13% of population) with BP >160/95 mm Hg and a further
46 million (21%) with BP 140/90-160/95 mm Hg
CV event
Acute MI
Heart failure
Stroke
All (95% CI)
Cost associated with
uncontrolled BP
Cost saving if BP target
attained
Events
Costs
Events
Costs
(000s)
(billion Euros)
(000s)
(billion Euros)
442
815
964
2220
2.22
2.99
5.09
10.3 (9.8,10.8)
19
122
141
281
0.09
0.45
0.72
1.26 (0.80,1.90)
Hansson et al Blood Press 2002
HF Prevention





Treat Hypertension
Early diagnosis and prompt treatment of
MI
Adequate treatment of RHD
Treat and prevent DM to prevent
Cardiomyopathy DM
Early diagnosis of Myocarditis to prevent
cardiomyoptahy
Adequate and prevent recurrence
of RHD




Recognition of acute rheumatic fever
Prompt treatment
AB prophylaxis
Refer to cardiologist
HF Prevention





Treat Hypertension
Early diagnosis and prompt treatment of
MI
Adequate treatment of RHD
Early diagnosis and refer congenital heart
disease
Early diagnosis of Myocarditis to prevent
cardiomyoptahy
Prevent development of HF in
congenital heart disease



Early diagnosis
Sent to cardiologist at proper time
AB prophylaxis
HF Prevention





Treat Hypertension
Early diagnosis and prompt treatment of
MI
Adequate treatment of RHD
Treat and prevent DM to prevent
Cardiomyopathy DM
Early diagnosis of Myocarditis to prevent
cardiomyoptahy
Prevent cardiomyopathy



Carditis : Viral, RHD, etc
PPCM, SLE
Prevent by early diagnosis and prompt
treatment
Summary


High mortality and morbidity of HF
Preventable by HF Risk factor intervention,
Early diagnosis and prompt treatment