HEART FAILURE

CONGESTIVE HEART FAILURE

• Inability of the heart to pump sufficiently to

meet metabolic needs, leading to decreased
tissue perfusion as a result of decreased
cardiac output
• Acute or chronic
• Systolic or diastolic
 Heart failure mortality statistics
Mortality rates in heart failure are high even for patients compliant with the
best available treatments1

~50 %
DIE WITHIN
5 YEARS OF DIAGNOSIS

The impact of heart failure on individuals is significant, and the worldwide

prevalence is high

1. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008. 2. Gerber et al. JAMA Intern Med
2015;175:996-1004 and Zarrinkoub et al. European Journal of Heart Failure 2013;15: 995–1002
 Heart failure mortality statistics

Sudden death is the most frequent cause of cardiovascular (CV) mortality

among systolic heart failure patients1*

~45 %
OF CARDIOVASCULAR DEATHS
ARE DUE TO SUDDEN DEATH*

1. Desai A.S. et al, Effect of angiotensin-receptor-neprilysin inhibitor LCZ696 compared with Enalapril on mode of death in heart failure patients, European Heart Journal, 2015;
2. Mozaffarian D, Benjamin EJ, Go AS, et al; for American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2015
update: a report from the American Heart Association. Circulation. 2015;131(4):e29-e322.
 Heart failure mortality statistics

Despite improvements in care, 1-year mortality rates for heart failure

patients remain high

1 4 IN OF HEART FAILURE PATIENTS

DIE WITHIN 1 YEAR
OF DIAGNOSIS

1. Gerber et al. JAMA Intern Med 2015;175:996-1004. 2. Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-
Hill; 2008. 3. Mann DL, Zipes DP, Libby P, Bonow RO, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 10th ed. Philadelphia: Saunders; 2015.
 Heart failure mortality statistics

All heart failure patients, even those who are considered asymptomatic
(NYHA class I) or mildly symptomatic (NYHA class II), are at high risk of dying1

IN A CLINICAL TRIAL WITH MEDIAN FOLLOW-UP OF ~3YEARS

34 %
42 %

OF NYHA CLASS I AND II OF NYHA CLASS III AND IV

PATIENTS DIED PATIENTS DIED

1. Ahmed A. A propensity matched study of New York Heart Association class and natural history end points in heart failure. Am J Cardiol. 2007;99(4):549-553. 2. Fauci AS,
Braunwald E, Kasper DL, et al, eds. Harrison's Principles of Internal Medicine. 17th ed. New York: McGraw-Hill; 2008. 3. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA
guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation. 2013;128(16):e240-e327.
 CLASSIFICATION OF HEART FAILURE

• Acute HF (Acute decompensated HF) :

o Warm and dry (well-compensated HF)
o Warm and wet (congested without evidence of low cardiac output)
o Cold and dry (low output without congestion)
o Cold and wet (low output with congestion, highest risk population)
• Acute HF :
o Left HF (dyspnea, orthopnea, pulmonary edema),
o Right HF (venous distention, ascites, edema), or
o Combination of both.
• LV failure can be subdivided based on the presence of either systolic
or diastolic dysfunction (LV ejection fraction [LVEF] <40% = HFrEF)
versus diastolic dysfunction (LVEF ≥50% = HFpEF). ).
Another classification is HFmrEF (EF >40-49%)
• Chronic HF is categorized based on the NYHA functional class and
American Heart Association (AHA) disease stage
Relationship between end-diastolic volume and
stroke volume in normal and failing myocardium
 BNP = 600
BNP = 100-400

BNP = 400-1000 BNP = >1000

EF = SV / EDV X 100 %
 From myocardial infarction (MI) to HF:
Ventricular Remodeling after MI
Fibrous scar Myocyte hypertrophy

Acute
infarction
Increased
interstitial
collagen

Infarct zone thinning Spherical ventricular

and elongation dilation

Konstam MA, et al. J Am Coll Cardiol Img 2011;4:98–108

 Different co-morbidities and pathophysiological
processes can lead to different types of heart failure
A range of risk factors and co-morbidities contribute to the
development of HF1
Age
Smoking MI
Systolic
Obesity
dysfunction
Hypertension HFrEF
Coronary artery HFpEF
Diastolic
disease
LV dysfunction
Diabetes
Dyslipidemia hypertrophy

Normal LV structure Subclinical

and function LV remodeling LV dysfunction Clinical HF

Years Years/months

‡ Patients with an LV ejection fraction of 35–50% represent a ‘gray area’ and may have primarily mild systolic dysfunction2
HF=heart failure; LV=left ventricular; LVEF=left ventricular ejection fraction;MI=myocardial infarction
1. Krum, Gilbert. Lancet 2003;362:14758;
Figure reproduced with permission from Krum, Gilbert. Lancet 2003;362:147–58 Copyright © 2003 Elsevier
 Definition of heart failure with preserved (HFpEF), mid-
range (HFmrEF) and reduced ejection fraction (HFrEF)
Type of HF HFrEF HFmrEF HFpEF

1 Symptoms ± Symptoms ± Signs Symptoms ± Signs

Signs
2 LVEF <40% LVEF 40-49% LVEF ≥50%

C 3 -- 1. Elevated levels 1. Elevated levels

R of natriuretic of natriuretic
I
T
peptides peptides
E 2. At least one 2. At least one
R additional criterion: additional criterion :
I
A a. relevant structural a. relevant structural
heart disease heart disease
(LVH and/or LAE) (LVH and/or LAE)
b. diastolic b. diastolic
dysfunction dysfunction
 Patterns of ventricular remodeling are
different for HFrEF and HFpEF

Left ventricle
normal

HFrEF HFpEF
Volume Pressure
HFrEF – a condition of HFpEF – a condition of
overload overload
volume overload pressure overload
• characterized by Increased Increased • characterized by
diastolic pressure systolic pressure
eccentric hypertrophy concentric hypertrophic
growth
• results in thinning of the Increased Increased
LV walls, decreased diastolic wall stress systolic wall stress • results in normal sized
systolic function and − LV cavity with thickened
Series addition of new Parallel addition
enlarged LV volume sarcomeres of new myofibrils − walls and preserved
systolic function
Chamber Wall
enlargement thickening

Eccentric Concentric
hypertrophy hypertrophy
Left ventricle Left ventricle
volume pressure
overload overload

LV=left ventricular; HFpEF=heart failure with preserved ejection fraction; HFrEF=heart failure with reduced ejection fraction
Adapted from Colucci (Ed.). Atlas of Heart Failure, 5th ed. Springer 2008;
Figure reproduced with permission from Grossman W, et al. In: Perspectives in Cardiovascular Research; Myocardial Hypertrophy
and Failure. Vol 7. Edited by Alpert NR. New York: Raven Press; 1993:1–15. Copyright © 1993 Wolters Kluwer Health
 DIASTOLIC HEART FAILURE (HFpEF)
• A major contributor to the rise in HF hospitalizations has been HF
with preserved left ventricular systolic function (HF-PSF), known as
diastolic HF.

• Definition: Signs and symptoms of HF despite normal or near-

normal ejection fraction, and evidence of diastolic dysfunction.
• Abnormal left ventricular (LV) filling and elevated filling pressures
are the hallmark of this disease process. Patients with HF-PSF are
more likely to be elderly and/or female, and have hypertension or
diabetes.
• Patients with PSF were less likely to have a prior MI, and less likely
to be on ACE-Inhibitor or ARB therapy.

• Compared with patients with HF-RSF (HFrEF), patients with HF-

PSF (HFpEF) have nearly the same length of hospital stay, but a
slightly lower hospital mortality (3% vs. 4%).
 ETIOLOGY DIASTOLIC HF (HF-PSF , HFpEF)

• Hypertension: Over time, left ventricular hypertrophy (LVH) can

develop and cause increased wall thickness and abnormal relaxation.
• Coronary artery disease (CAD): Akinetic myocardium causes
decreased compliance during LV chamber filling. It also alters
metabolic pathways necessary for myocyte relaxation.
• Diabetes mellitus: Causes microvascular disease ─> LV
noncompliance during filling, and myocyte apoptosis and interstitial
fibrosis.
• Restrictive/infiltrative cardiomyopathy
• Hypertrophic cardiomyopathy
• Pericardial disease: including tamponade and constriction
• Right HF due to pulmonary hypertension
• Congenital heart disease
• Valvular disease such as severe stenosis or regurgitation
 PATHOPHYSIOLOGY DIASTOLIC HF IN CAD
• Coronary artery disease (CAD): Akinetic myocardium
causes decreased compliance, stiffness increased
from increased fibrosis/collagen deposition (from previous MI),
infiltrative processes, LVH, and chamber dilation during LV chamber
filling.
• It also alters metabolic pathways necessary for myocyte relaxation.
• Loss of normal relaxation patterns due to structural or functional
abnormalities, ─> increased filling pressures starting in the LV and
leading back to the left atrium (LA) and pulmonary vasculature.

• Abnormalities in myocyte relaxation, including calcium modulation,

decreased availability of ATP, and increased intracellular glycolysis.
• Upregulation of neurohormonal stimuli, including the RAAS and SNS.
• Relaxation is delayed or incomplete due to LVH or LV dysynchrony,
─> early diastolic filling.
• LV chamber dilation and restrictive filling ─> late diastolic filling.
Pathophysiology of Heart Failure (Systolic heart failure)
 DIAGNOSTIC CRITERIA

• HF is a clinical diagnosis based on history, physical exam, CXR.

• Although there are no universally agreed upon diagnostic criteria for
HF, the Framingham criteria require two major or one major and two
minor criteria:
o Major criteria: paroxysmal nocturnal dyspnea (PND), jugular
venous distention (JVD), crackles, cardiomegaly, pulmonary
edema, S3, hepatojugular reflux (HJR), and weight loss with
diuresis (>4.5 lb).
o Minor criteria: lower extremity edema, nocturnal cough, dyspnea
on exertion (DOE), hepatomegaly, pleural effusions,
tachycardia, and decrease in vital capacity.

• The diagnosis of HF is further supported by laboratory values:

o elevated brain natriuretic factor [BNP]) and
o imaging studies (cardiac dysfunction on echocardiogram)
 laboratories

• BNP is usually elevated in HF with PSF, though not to the

same degree as in systolic HF.
• Can help distinguish from non-HF causes of symptoms.
• BNP can falsely low in obese patients.
• Other laboratory testing:
o Blood glucose testing/HgbA1c for DM evaluation
o Iron studies: hemochromatosis, excessive transfusions.
o Genetic testing: such as storage disorders.
o Serum/urine protein electrophoresis: to evaluate for a protein gap
(overproduction and deposition) process such as amyloidosis.
o 5-Hydroxyindoleacetic acid (5-HIAA) testing if other features of
carcinoid syndrome and tricuspid disease are present.
 Brain Natriuretic Peptides
• High ventricular filling pressures stimulate the release of
ANP and BNP.

• Both peptides have diuretic, natriuretic, and

antihypertensive effects, which they exert by inhibiting the
renin-angiotensin-aldosterone system.

• They also have systemic and renal sympathetic activity.

• In addition, BNP may provide a protective effect against the

detrimental fibrosis and remodeling that occurs in
progressive heart failure.
 ECG and Imaging

The ECG :
• chamber enlargement and hypertrophy.
• It may provide evidence of ischemia and/or prior MI.
• Low voltage could indicate a restrictive process.

Echocardiography:
• Assessment of systolic function, chamber sizes, and hypertrophy.
• Also, valvular dysfunction such as mitral regurgitation or aortic
stenosis can lead to HF with PSF.
• Regional wall motion abnormalities indicating
ischemia and/or prior infarction can be identified.
• LVH indicates hypertrophic cardiomyopathy.
• Infiltrative/restrictive processes can also be identified.
• Diastolic function is evaluated by using LV filling
patterns.
 SYMPTOMS AND SIGNS TYPICAL OF HF
SYMPTOMS
TYPICAL
Breathlessness, Orthopnea, PND,
Reduce exercise tolerance, Fatigue,
tiredness, increasing time to recover
after exercise, Ankle swelling.
LESS TYPICAL
Nocturnal cough, Wheexing, Bloated
feeling, Loss of appetite, Confusion,
(especially in the elderly). Depression,
Palpitation, Dizzziness, Syncope,
Bendopnea.
SIGNS
MORE SPECIFIC
Elevated JVP, Hepatojugular reflux, S3
(gallop rhythm), Laterally displaced
apical impulse.
LESS SPECIFIC
Weight gain (2 kg/week), Weight loss
(in advanced HF), Tissue wasting
(cachexia), Cardiac murmur,
Peripheral edema, Pulmonary
crepitation, Pleural effusion,
Tachycardia, Irregular pulse,
Tachypnea, Cheyne Stokes
respiration, Hepatomegaly, Ascites,
Cold extremitas, Oliguria, Narrow
pulse pressure.
 NYHA Functional Classification of HF
Severity based on symptoms and physical activity

Class I No limitation of physical activity. Ordinary physical

activity does not cause undue fatigue, palpitation or
dyspnea.
Class II Slight limitation of physical activity. Comfortable at
rest, but ordinary physical activity results in fatigue,
palpitation, or dyspnea.
Class III Marked limitation of physical activity. Comfortable at
rest, but less than ordinary activity results in fatigue,
palpitation or dyspnea.
Class IV Unable to carry on any physical activity without
discomfort. Symptoms at rest. If any physical activity
is undertaken, discomfort is increased.
 ACC/AHA Stages of HF
Based on structure and damage to heart muscle

Stage A At high risk for developing HF. No identified

structural or functional abnormality; No signs or
symptoms.
Stage B Developed structural heart disease that is
strongly associated with the development of HF,
but without signs or symptoms.
Stage C Symptomatic HF associated with underlying
structural heart disease.

Stage D Advanced structural heart disease and marked

symptoms of HF at rest despite maximal medical
therapy.
 ACC / AHA Classification of CHF 2001

STAGE DESCRIPTION
A
High Risk For Hypertension, Diabetes Mellitus, CAD,
Developing Heart Family History of Cardiomyopathy
Failure

B Previous MI, LV Dysfunction,

Asymptomatic
Valvular Heart Disease
Heart Failure

C Structural Heart Disease, Dyspnea and

Symptomatic Fatigue, Impaired Exercise Tolerance
Heart Failure

D Marked Symptoms at Rest Despite

Refractory End-stage Maximal Medical Therapy
Heart Failure
 Patterns of ventricular remodeling are
different for HFrEF and HFpEF

LV
normal
HFrEF HFpEF
Volume Pressure
HFrEF – a condition of HFpEF – a condition of
overload overload
volume overload pressure overload
• characterized by Increased Increased • characterized by
diastolic pressure systolic pressure
eccentric hypertrophy concentric
hypertrophic growth
• results in thinning of Increased Increased
the LV walls, diastolic wall stress systolic wall stress • results in normal sized
decreased systolic − LV cavity with
Series addition of new Parallel addition
function and enlarged sarcomeres of new myofibrils − thickened walls and
LV volume preserved systolic
Chamber Wall function
enlargement thickening

Eccentric Concentric
hypertrophy hypertrophy
Left ventricle Left ventricle
volume pressure
overload overload
 Precipitating factors in patients
admitted with worsening heart failure

 Myocardial ischemia or infarct

 Excessive salt intake
 Noncompliance with medication
 Iatrogenic volume overload,  blood transfusion
 Lack of patient knowledge about their HF
 Arrhythmias,  atrial fibrillation (AF)
 Comorbidities -> pneumonia, influenza, uncontrolled DM
 Adverse drug effects  NSAIDs, alcohol, digoxin
 TREATMENT
• Unlike HF with RSF (Systolic HF), there are very few clinical
trials to direct optimal medical therapy in patients with HF
with PSF (Diastolic HF).

• No specific medications have been found to decrease

morbidity and mortality from HF with PSF (Diastolic HF).

• Therapy is directed at symptom control, BP and dietary

monitoring, and any possible underlying etiologies such as
ischemia or restrictive/infiltrative processes.

• BP goal of <130/80 mmHg may be warranted.

 MEDICATION
• Loop diuretics : for volume control and maintenance of
euvolemia.
• Thiazide diuretics can help with volume, but is generally
reserved more for treating hypertension.
• ACE inhibitors and ARBs are recommended in patients with
history of CAD or those with coronary risk factors including DM.
• The HOPE study : Multiple coronary risk factors, ramipril
reduced the annual risk of developing HF by 23% and by 33% in
those with systolic blood pressure (SBP) >139 mmHg.
• CHARM-Preserved trial : Candesartan therapy in patients with
New York Heart Association (NYHA) class II to IV HF with LVEF
>40% ─> reduced hospitalizations and cardiovascular death
• The I-PRESERVE : Irbesartan in NYHA II-IV and EF >45%
• β-Blockers :
 Medication :
• β-Blockers : in those with prior MI or atrial fibrillation.
• A small prospective cohort suggests a possible reduction in
number of hospitalizations of patients with diastolic
dysfunction and stable CAD who were using β-blockers.

• Calcium channel blockers : in those with symptom-limiting

angina or AF requiring rate control and have intolerance to
β-blockers.

• In addition to decreasing heart rate, can facilitate calcium

signaling to decrease wall tension (“lusitropic effect”).
 OTHER NONPHARMACOLOGIC THERAPY
• Restoration of sinus rhythm is of potential benefit.
• When loss of atrial contribution occurs, LV filling in an already
noncompliant heart becomes even worse.
• Combined with the predisposition to tachycardia, sinus rhythm is
theorized to be of benefit.
• Consider in patients who are still symptomatic despite adequate
rate control.

• Amiodarone and dofetilide have been shown to increase

conversion to and maintenance of sinus rhythm in HF patients.

• Early experience with catheter ablation also suggests

improvement in symptoms for HF patients.
 Differences between pharmacologic treatment of
systolic and diastolic heart failure
• β-Blockers are now recommended for treatment of both systolic
and diastolic HF.
• In diastolic HF : β-Blockers  decrease HR, increase the duration
of diastole, modify the hemodynamic response to exercise.
• In systolic HF : β-Blockers are used chronically to increase
inotropic state and modify LV remodelling.
• In systolic HF : β-Blockers must be titrated slowly and carefully.
This is not necessary in diastolic HF.
• Diuretics are used in systolic HF and diastolic HF.
But the doses in diastolic HF smaller then in systolic HF.
• CCB : such diltiazem, nifedipine, verapamil have no place in the
treatment of systolic HF. By contrast, these drugs useful in the
treatment of diastolic HF.
 European Society of Cardilogy Congress
ROMA 2016

Pharmacological treatments recommended in patients

with symptomatic (NYHA class II-IV) HFrEF (Systolic HF)

 ACE-inhibitors, in addition to beta-blocker for symptomatic HFrEF

to reduce the risk of HF hospitalization and death.

 Beta-blocker, in addition to ACE-inhibitors for patient with stable,

symptomatic HFrEF to reduce the risk of HF hospitalization and
death.

 An MRA for patients with HFrEF who remain symptomatic despite

treatment with ACE-I and BB to reduce the risk of HF hospitalization
and death
 \Other pharmacological treatments recommended in selected
patients with symptomatic (NYHA II-IV) HFrEF (Systolic HF)

 Diuretics are recommended in order to improve symptoms and exercise

capacity in patients with signs and/or symptoms of congestion. to
reduce the risk of HF hospitalization.
 Angiotensin receptor neprilysin inhibitor : Sacubitril/valsartan is
recommended as a replacement for an ACE-I to further reduce the risk of
HF hospitalization and death despite optimal treatment with an ACE-I (or
ARB), BB, and MRA.
 If channel-inhibitors : Ivabradine should be considered to reduce the risk
of HF hospitalization with EF ≤ 35 %, in sinus rhythm and HR ≥ 70 bpm
despite treatment with BB, ACE-I(ARB) and MRA.
 Hydralazine and ISDN : should be considered in black patient with EF
<35%-45% combined with a dilated LV with dilated LV NYHA III-IV to
reduced the risk of death.
 Digoxin may be considered in symptomatic patients in sinus rhythm
despite treatment with ACE-I (ARB), BB, MRA to reduce the risk of
hospitalization
 Treatment of HFpEF (Diastolic HF)

 No treatment has been shown, convincingly, to reduce

morbidity or mortality in patients with HFpEF or HFmrEF.
 Diuretics will usually improve congestion for HFpEF and
HFmrEF.
 Evidence that BB and MRA improve symptoms is lacking.
 ARB (only candesartan) and ACE-I improve NYHA class.
 For patients in sinus rhythm, there is some evidence that
nevibolol, digoxin, spironolactone and candesartan might
reduce HF hospitalizations.
 For patients in AF, BB do not appear to be effective and
digoxin has not been studied.
INI SAJA DULU