Heart  Failure:

pathophysiology
Prof.V.Grabauskienė,  2017  m.
What  kind  of  diseases  
people    afraid  most  
often  ???

but
People  died  most  often  
from  Cardiovascular  
Diseases  ???
 Heart  diseases progression
cascade
Miocardial
Coronary   infarction
thrombosis Arrhythmia   Sudden  death
&  LV  disfunction
Mickardial  
Silent
ishemia     Angina  
Hibernation Remodeling
CHD LV  
Stroke dilatation

Atherosclerosis  
LVH   Chronic  HF

Risk  faktors
(CHOL,  HT,  diabetes,  smoking    
Stress,  obesity,  lack  of  physical  activity,  ….. E.Braunwald
Mainstreams  in  medicine
Past   EVIDENCE  BASED
Imaging
Biomarkers  ….

Now PREDICTIVE
PREVENTIVE
PERSONALIZE
Molecular  biology
Genetics  ….
 Heart  failure  stages
ACC/AHA  
Stages

NYHA
Funct  Class
 HF  ETIOLOGY

Myocardial  12.9% Other:

Heart  rhytm  disorders.

Other  
11.3% Anemia
Renal    disfuncion
Hypertension  7.2% CHD Cardiodepressiv  drug
Alkohol  ……
68.5%
Treatable    factors

80  %  cases – we  can  avoid  HF !!!

 STAGES,  PHENOTYPES  AND  
TREATMENT  OF  HF
At Risk for Heart Failure Heart Failure

STAGE A STAGE B STAGE C

At high risk for HF but Structural heart disease Structural heart disease STAGE D
without structural heart but without signs or with prior or current Refractory HF
disease or symptoms of HF symptoms of HF symptoms of HF

e.g., Patients with:

• HTN
• Atherosclerotic disease
e.g., Patients with: e.g., Patients with:
• DM Refractory
• Previous MI e.g., Patients with:
• Obesity Development of symptoms of HF • Marked HF symptoms at
Structural heart • LV remodeling including • Known structural heart disease and
• Metabolic syndrome disease
symptoms of HF at rest, despite rest
LVH and low EF • HF signs and symptoms
or
• Asymptomatic valvular
GDMT • Recurrent hospitalizations
Patients despite GDMT
disease
• Using cardiotoxins
• With family history of
cardiomyopathy

HFpEF HFrEF

THERAPY THERAPY THERAPY THERAPY THERAPY

Goals Goals Goals Goals Goals
• Control symptoms • Control symptoms
• Heart healthy lifestyle • Prevent HF symptoms • Control symptoms • Patient education • Improve HRQOL
• Prevent vascular, • Prevent further cardiac • Improve HRQOL • Prevent hospitalization • Reduce hospital
coronary disease remodeling • Prevent hospitalization • Prevent mortality readmissions
• Prevent LV structural • Prevent mortality • Establish patient’s end-
abnormalities Drugs Drugs for routine use of-life goals
• ACEI or ARB as • Diuretics for fluid retention
Strategies • ACEI or ARB Options
Drugs appropriate • Identification of comorbidities • Beta blockers • Advanced care
• ACEI or ARB in • Beta blockers as
• Aldosterone antagonists measures
appropriate • Heart transplant
appropriate patients for Treatment
vascular disease or DM • Diuresis to relieve symptoms Drugs for use in selected patients • Chronic inotropes
In selected patients • Hydralazine/isosorbide dinitrate • Temporary or permanent
• Statins as appropriate of congestion
• ICD • ACEI and ARB MCS
• Revascularization or • Follow guideline driven • Digoxin • Experimental surgery or
valvular surgery as indications for comorbidities, drugs
appropriate e.g., HTN, AF, CAD, DM In selected patients • Palliative care and
• Revascularization or valvular • CRT hospice
• ICD • ICD deactivation
surgery as appropriate
• Revascularization or valvular
surgery as appropriate

You    will  use  it  in  clinical  

practice
Epidemiology  Heart  Failure:
The  Problem
 Explanation  of  the  
terms:
• Myocardial failure = abnormalities reside in the myocardium and lead
to inability of myocardium to fulfilling its function

• Circulatory failure = any abnormality of the circulation

responsible for the inadequacy in body tissue
perfusion, e.g. decreased blood volume, changes
of vascular tone, heart functiones disorders

• Congestive heart failure = clinical syndrome which is developed

due to accumulation of the blood in front
of the left or right parts of the heart
Definition  of  Heart  Failure:  CHF  (1)
Inability  of  the  heart  to  meet  the  
peripheral  demands  under  rest  or  
exercise  conditions  caused  by  
– muscular dysfunction (systolic/diastolic)
– mechanical disorder (valve disease)
– combination
Definition  of  Heart  Failure:  CHF  (2)
• Definition  by  activity
– resting  HF
– exercise  HF
•  Definition  by  time  course
– Acute  
– Chronic
Definition  of  Heart  Failure:  CHF  (3)

• New  York  Heart  Association  (NYHA)

– I -­ no  visible  signs  and  symptoms

– II -­ signs  and  symptoms  at  high  level  
exercise  
– III -­ signs  and  symptoms  at  low  level  
exercise
– IV -­ no  physical  exercise  possible,  bed  
rest    necessary  

Most  valid  functional  definition  throughout  the  world!  

Definition  of  Heart  Failure  CHF  (4)
Anatomical  definition

–Left  sided  heart  failure  

•  CHD  (myocardial  infarction)  
•  disease  of  mitral  or  aortic  valve  
•  Cardiomyopathy  of  unknown  origin  (idiopathic)  

– Right  sided  heart  failure  

•  Pulmonary  embolism  
•  Pulmonary  vascular  hypertension  
•  Mitral  stenosis
THE  PULMONARY  AND  SYSTEMIC  
CIRCULATION
Pulmonary   Lungs
circulation
Oxygenated
Deoxygenated

Right
atrium Left
atrium

Systemic  
circulation Right Left
ventricle ventricle

Body
tissue
Heart  Failure:  Haemodynamics  
For  yourself  analysis
 Acute  heart  failure:  etiology
•  Acute HF  (left  sided:  pulmonary  edema)  
– Myocardial  infarction  (w/wo  cardiogenic  
shock)
– Hypertensive  heart  disease  
•  Acute  CHF:  hypertensive  crisis-­pulmonary  edema
– Inflammation  
•  Acute  valvular  disease  (endocarditis)  
•  Acute  (peri-­)myocarditis
•  Combination  (pancarditis)
– Pulmonary  embolism  (right  sided  CHF)
 Cardiogenic  shock:  etiology
•  Special  subset  of  HF:
Cardiogenic  shock  
– sudden  onset  with  underlying  disease  (often  
triggered  by  large  or  multiple  myocardial  
infarction);;  leading  to:  
•  organ  perfusion  deficit  
•  organ  failure  
•  fast  development  of  irrevesibilty  
•  organ  death,  clinical  death,  biological  death
– Despite  therapeutic  improvement  (PCI,  
IABP)  50-­70%  mortality  rate
 Left  heart  failure
•  Acute     •  Low  output  
– Pulmonary  edema                                          – Classical  term:  CHD,
– Cardiogenic  shock                                              HPT,  RHD  etc.  
•  Chronic             •  High  output  
– NYHA  I-­IV                                                             – Fever  states
– Anemia
– Pregnancy  
– Hyperthyreoidism
– AV  fistulas  …  
 Right  heart  failure
•  Acute  
– Pulmonary  embolism
– Right  atrial  masses  (myxoma)

•  Chronic
– Mitral  stenosis  
– Pulmonary  stenosis
– Deep  Vein  Thrombosis  
– Idiopathic  PAH
– Acquired  PAH  
Chronic  left  heart  failure  
Most  common  endpoint  
of  multiple  disorders  of  
the  left  ventricle
 Etiology  of  HF
•  Chronic  HF
– Hypertensive  heart  disease:  progressive  
muscle  damage;;  hypertrophy;;  diastolic  HF
– Coronary  heart  disease:  myocardial  
infarction  
– Valvular  disease after  acute/occult  onset  
of  endocarditis  
– Chronic  myocarditis  -­ „secondary“
cardiomyopathy
– „Primary“ dilatative  cardiomyopathy  
– Venous  disease  (deep  vein  thrombosis)  -­
right   heart  failure
Pathophysiology  of  Heart  Failure

•  Manifestation  types  of  heart  failure

– Systolic  dysfunction
– Diastolic  dysfunction
– Muscular  hypertrophy  
– Dilatation  and  remodeling
 PATHOPHYSIOLOGY-­
STRUCTURAL  CHANGES  WITH  HF

• Dec.  contractility
In the most forms of HF the contractility of myocardium is
decreased (ischemia, hypoxia, acidosis, inflammation, toxins
metabolic disorders... )
• Inc.  preload  (volume)
• Inc.  afterload  (resistance)
• **Ventricular  remodeling  (ACE  inhibitors  can  prevent  this)
• Ventricular  hypertrophy
• Ventricular  dilation
Causes  of  heart  pump  failure
A.  MECHANICALABNORMALITIES
1.  Increased  pressure  load
– central  (aortic  stenosis,  aortic  coarctation...)
– peripheral  (systemic  hypertension)

2.  Increased    volume  load

– valvular regurgitation
– hypervolemia

3.  Obstruction  to  ventricular  filling

– valvular  stenosis
– pericardial  restriction
Causes  of  heart  pump  failure
B.  MYOCARDIAL  DAMAGE
1.  Primary
a)  cardiomyopathy
b)  myocarditis
c)  toxicity (e.g.  alcohol)
d)  metabolic abnormalities  (e.g.  hyperthyreoidism)

2.  Secondary
a)  oxygen deprivation  (e.g.  coronary  heart  disease)
b)  inflammation  (e.g.  increased  metabolic  demands)
c)  chronic obstructive  lung  disease
Causes  of  heart  pump  failure
C.  ALTERED  CARDIAC  RHYTHM

1. ventricular flutter  and  fibrilation

2.  extreme tachycardias
3.  extreme bradycardias
 Myocardial  contractility
Contractility  of  myocardium
Changes in  ability  of  myocardium  to  develop the  force  
by  contraction  that  occur independently  on the
changes  in  myocardial  fibre  length

Mechanisms  involved  in  changes  of  contractility

• ­ amount  of  created  cross-­bridges  in  the    

sarcomere by  ­ of  [Ca  ++]i concentration

-­ catecholamines ® ­[Ca++]i® ­ contractility

-­ inotropic  drugs  ® ­[Ca++]i® ­ contractility
 DEFINITION-­HEART  FAILURE  (HF)
KEY  CONCEPTS
• CO  =  SV  x  HR-­becomes  insufficient  to  meet    
metabolic  needs  of    body
• SV-­ determined  by  preload,  afterload  and  myocardial  
contractility
• EF<  40% (need  to  understand)
• *Classifications  HF
• Systolic  failure-­ dec.  contractility
• Diastolic  failure-­ dec.  filling
• Mixed
90/140= 64% EF- 55-65 (75) normal

A  low  ejection  fraction  could  be  a  sign  

that  the  heart  is  weakened.  
 PATHOPHYSIOLOGY-­
STRUCTURAL  CHANGES  WITH  HF

• Dec.  contractility
• Inc.  preload  (volume)
• Inc.  afterload  (resistance)
• **Ventricular  remodeling  (ACE  
inhibitors  can  prevent  this)
• Ventricular  hypertrophy
• Ventricular  dilation
Pathophysiology  of  Heart  Failure:
function  control  
•  Determinants  of  heart  function
– Normal  conditions  
•  Nervous  (sympathetic)  control  
– Heart  rate
– Contractility  
– Abnormal  conditions  
•  Pressure  volume  control:  Frank-­Starling  
mechanism  (FSM)
– Preload  
– Afterload
 General  pathomechanisms  involved  
in  heart  failure  development
Cardiac  mechanical  dysfunction  can  develop as  
a  consequence  in  preload,  contractility  and  afterload  
disorders
Disorders of preload:
­­ preload ® length  of  sarcomere  is  more  than    optimal  ®
® ¯ strength  of  contraction

¯¯ preload ® length  of  sarcomere  is  well  below  the optimal
® ¯ strength  of  contraction

Important: failing  ventricle  requires  higher  end-­diastolic volume  

to  achieve  the  same  improvement  of  CO  that    normal
ventricle  achieves with  lower  ventricular  volumes
 Preload
Stretching the myocardial fibers during diastole  by  
increasing end-­diastolic volume ® ­force of  contraction
during systole =  Starling´s law

preload =  diastolic  muscle  sarcomere  length  leading  to  

increased  tension  in  muscle    before  its  contraction

- venous  return  to  the  heart  is  important  ® end-­diastolic

volume  is  influenced  
- stretching  of  the  sarcomere  maximises  the  number  
of  actin-­myosin  bridges  responsible  for  development  of  force

-­ optimal  sarcomere  length  ~ 2.2  µm

 Preload    (volume)
BODY  FLUID  VOLUME  HYPOTHESIS

High-­output Low-­output
Cardiac  Failure Cardiac  Failure

¯ Peripheral ¯ Cardiac
Vascular  Resistance Output

Arterial  Underfilling

Non-­Osmotic Sympathetic Renin-­Angiotensin-­

AVP  Release Nervous  System Aldosterone  System

Diminished
Renal  Haemodynamics
and
Renal  Sodium  &  Water
Retention
AVP  =  arginine  vasopressin
IMPORTANCE  OF  PRELOAD  IN  
CHF

• An  adequate  preload  is  necessary  to  

maintain  cardiac  output  (Frank  Starling)
• Preload  is  synonymous  with  end-­
diastolic  volume  or  pressure
• Increases  in  preload  are  associated  with  
increases  in  cardiac  output
• Failing  hearts  are  less  responsive  to  
changes  in  preload
 Afterload
It  is  expressed  as  tension  which  must  be  developed in  the  wall  of  
ventricles  during  systole  to  open  the  semilunar  valves and  eject  
blood  to aorta/pulmunary  artery

Laplace  law:
intraventricular pressure  x  radius  of  ventricle
wall  tension  =  -­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­-­
2  x ventricular  wall  thickness

Disorders  of  afterload due  to:

fluid  retention in  the  body
­ arterial  resistance
valvular heart  diseases  (  stenosis )

¯ afterload -­ ¯ arterial  resistance   ­ afterload -­ ­arterial resistance

due  to:                -­ myocardial  hypertrophy due  to:            -­ myocardial  hypotrophy
-­ ¯ ventricular  size -­­ ventricular  size
 Factors  effecting    heart  pump
(Contractility)    effectiveness  

PRELOAD Afterload
• Volume  of  blood  in   •Force  needed  to  eject  blood  
ventricles  at  end  diastole into  circulation
• Depends  on  venous  return •Arterial  B/P,  pulmonary  artery  
pressure
• Depends  on  compliance •Valvular  disease  increases  
afterload
 PATHOPHYSIOLOGY-­
STRUCTURAL  CHANGES  WITH  HF

• Dec.  contractility
• Inc.  preload  (volume)
• Inc.  afterload  (resistance)

• **Ventricular  remodeling  
(ACE  inhibitors  can  prevent  this)
• Ventricular  hypertrophy
• Ventricular  dilation
Myocardial  remodeling  –
changes  in  ventricular  geometry
 LEFT  VENTRICULAR  
REMODELING
MACROSCOPIC  CHANGES  

• é end  diastolic  volume

• é end  systolic  volume

• changes  of  ventricular  shape  

(ésphericity-­ )  

• é LV  mass
 LEFT  VENTRICULAR  
REMODELING
OTHER  CHANGES:

• Systolic  and  diastolic  dysfunction  

• Changes  in  ultrastructure  level  

• Changes  in  genes  expresion  

• metabolic  dysfunction
 Left  ventricular  remodeling
Changes  in  ultrastructure  level  

• Intersticial    fibrosis
• Hypertrophy  of  myocite  
• Myocite  “slippage”
• Apoptosis
• Infarct  expansion  
Main  causes  and  mechanisms  involved
in  pathological  remodelation  of  the  heart
1.  ­amount  and  size of  myocytes =  hypertrophy
Due  to: -­ ­ volume  and/or    pressure  load  
(excentric,  concentric  hypertrophy)

- hormonal  stimulation  of  cardiomyocytes  by  

norepinephrine,  angiotenzine  II

2.  ­%  of non-­myocytic cells in  myocardium and  their

influence on  structure and  function of  heart
a. endothelial  cells – endothelins : mitogenic ability  ®
® stimulation  growth  of  smooth  muscle  cells  of  vessels,  fibroblasts
Hypertrophy
b. fibroblasts -­ ­ production  of  kolagens -­ Fibrosis
Causes  leading  to  changes  of  number  
and  size  of  cardiomyocytes  

Ischemia Hyperthrophy,  fibrosis

 CHD

LV  remodeling

SVD
AH MVI,
AoS AoVI

Virus
 TYPES  OF  HEART  FAILURE
• Low-­Output  Heart  Failure
• Systolic  Heart  Failure:  
• Decreased  cardiac  output
• Decreased  Left  ventricular  ejection  fraction
• Diastolic  Heart  Failure:  
• Elevated  Left    and  Right  ventricular  end-­diastolic  pressures
• May  have  normal  LVEF

• High-­Output  Heart  Failure

• Seen  with  peripheral  shunting,  low-­systemic  vascular  resistance,  
hyperthryoidism,  carcinoid,  anemia
• Often  have  normal  cardiac  output

• Right-­Ventricular  Failure
• Seen  with  pulmonary  hypertension,    large  RV  infarctions.
 CAUSES  OF  LOW-­OUTPUT  HEART  
FAILURE
• Systolic  Dysfunction
• Coronary  Artery  Disease
• Idiopathic  dilated  cardiomyopathy  (DCM)
• 50%  idiopathic  (at  least  25%  familial)
• 9  %  mycoarditis (viral)
• Secondary  DCM:  Ischemic,  peripartum,  hypertensive,  
connective  tissue  disease,  substance  abuse,  doxorubicin  and  
oyher toxins
• Hypertension
• Valvular Heart  Disease
• Diastolic  Dysfunction
• Hypertension
• Coronary  artery  disease
• Hypertrophic  obstructive  cardiomyopathy  (HCM)
• Restrictive  cardiomyopathy
Pathophysiology  of  Heart  Failure:
Systolic  vs  diastolic
•  Schematic  manifestation  
of  systolic  and  diastolic  
dysfunction:  stiff  or  
enlarged  ventricle
•  Stiffness  caused  by  
either  hypertrophy,  
inflammation  or  storage  
diseases  (amyloid)
•  Enlargement  caused  by  
increase  of  collagen  (scar)  
deposition  and/or  tension  
load
 HEART  FAILURE
ETIOLOGY  AND  
PATHOPHYSIOLOGY
• Systolic  failure-­ most  common  cause          
• Hallmark  finding:  Dec.  in  *left  ventricular  ejection  
fraction  (EF)
• Due  to  

• Impaired  contractile  function    (e.g.,  MI)

• Increased  afterload  (e.g.,  hypertension)
• Cardiomyopathy
• Mechanical  abnormalities  (e.g.,  valve  disease)
 HEART  FAILURE
ETIOLOGY  AND  
PATHOPHYSIOLOGY

• Diastolic  failure
• Impaired  ability  of    ventricles  to  relax  and  fill  during  
diastole  >    dec.  stroke  volume  and  CO
• Diagnosis  based  on    presence  of    pulmonary  
congestion,  pulmonary  hypertension,  ventricular  
hypertrophy
• *normal  ejection  fraction  (EF)-­ Know  why!
Characteristic  features  of  systolic  
dysfunction  (systolic  failure)

•  ventricular  dilatation

•  reducing  ventricular  contractility  (either  generalized

or  localized)

•  diminished  ejection  fraction  (i.e.,  that  fraction  of  end-­diastolic

blood  volume  ejected  from  the  ventricle  during  each  systolic  
contraction  – less  then  45%)

•  in  failing  hearts,  the  LV  end-­diastolic  volume  (or  pressure)

may  increse  as  the  stroke  volume  (or  CO)  decreases
Characteristic  features  of  diastolic  
dysfunctions  (diastolic  failure)
• ventricular  cavity  size  is  normal  or  small

•  myocardial  contractility  is  normal  or  hyperdynamic

•  ejection  fraction  is  normal  (>50%)  or  supranormal

•  ventricle  is  usually  hypertrophied  

•  ventricle  is  filling  slowly  in  early  diastole  (during  the  period  
of  passive  filling)
• end-­diastolic  ventricular  pressure  is  increased
 DIAGNOSTIC  CRITERIA:
HF  WITH  REDUCED  VS.  HF  WITH  
PRESERVED  EF
Clinical evidence of HF:
Clear clinical presentation of HF
or Framingham or Boston criteria
If uncertain:
Plasma BNP
or chest x-ray
or cardiopulmonary exercise testing

LVEF < 50% LVEF ≥ 50%

Supportive evidence:
Supportive evidence: Concentric LVH or remodeling
Eccentric LVH or remodeling Left atrial enlargement in absence of AF
Echo Doppler or catheter evidence of
Exclusions: Non-myocardial disease diastolic dysfunction

Adapted from Yturralde FR. Prog Exclusions: Non-myocardial disease

Cardiovasc Dis 2005;47:314-19
 Etiology  of  HF  with  Reduced  vs.  HF  with  Preserved  LVEF

HF with Reduced EF HF with Preserved EF

Non- Myocardialb Non- Myocardialb

Myocardiala Myocardiala
Hypertension Hypertension

CAD CAD
Valvular
Diabetes Diabetes
Valvular disease
disease Cardiomyopathy AS, AR, Cardiomyopathy
AS, AR, genetic, post-
MR, MS genetic, post-
MR, MS partum, viral, partum, viral,
drug/radiation Pericardial drug/radiation
constraint
High output
Infiltrative
constriction,
Anemia, AV Infiltrative
myopathyc tamponade myopathyc
fistula

a = cause of HF or specific target for therapy High output

b = disease process that may lead to HF Anemia, AV
c = may have stage in which EF is normal, but often declines fistula
 HEART  FAILURE
ETIOLOGY  AND  
PATHOPHYSIOLOGY

• Mixed systolic  and  diastolic  failure

• Seen  in  disease  states  such  as  dilated  cardiomyopathy  
(DCM)
• Poor  EFs  (<35%)
• High  pulmonary  pressures
• Biventricular  failure  (both  ventricles      may  be  dilated  and  
have  poor  filling  and  emptying  capacity)
 CONCEPTS ON  THE  
PATHOGENESIS OF CHF

• 1970s Contractile  performance

• 1980s Haemodynamic  concept

• 1990s Neuroendocrine  model

 THE  CHF  MODELS:
• Haemodynamic  (Pump)

• Cardiorenal  (Oedema)

• Neurohormonal  (SNS,  RAAS)

• Molecular-­cellular  (Cytokines….)

• LV  remodelling
 Essential  functions  of  the  heart  are  secured  
by  integration  of  electrical  and  mechanical
functions  of  the  heart
Cardiac  output  (CO)  =  heart  rate  (HR)  x  stroke  vol.(SV)

- changes  of  the  heart  rate

- changes  of  stroke  volume

• Control  of  HR:

-­ autonomic  nervous  system
- hormonal(humoral)  control

• Control  of  SV: -­ preload

-­ contractility
-­ afterload
 HF: NEUROENDOCRINE    ACTYVATION
AND  MORTALITY

CONSENSUS I data

70

60
P<0.01
50

40 Noradrenaline
Angiotensin II
30
Aldosteron
20

10

0
1 2 3 4

Adaptuota iš Swedberg et al. Circulation, 1990

 PLASMA  NOREPINEPHRINE  AND  
PROGNOSIS  IN  SEVERE  HF

Relationship  of  plasma  norepinephrine  to  probability

of  survival  in  patients  with  severe  CHF
1.0
Probability  of  Survival

0.8

0.6 PNE  <400  pg/ml

0.4 n=106

0.2
PNE  400-­800  pg/ml
PNE  >800  pg/ml
0.0
0 10 20 30 40 50 60
Elapsed  Time  (months)

Adapted  from  Cohn  J  et  al.  N  Engl  J  Med  1984

Pathophysiology  of  chronic  CHF:
peripheral  effects  
• Activation  of  the  neurohumoral  system  
– Activation  of  renal-­adrenal  system  (renin-­
angiotensin-­aldosterone  system  -­RAAS)
– Activation  of  cardiac  RAAS  
– Disregulation  of  number  and  properties  of  
cardiac  ß-­adrenoceptors  (ß-­AR)  
 THE VICIOUS  CYCLE  OF  CONGESTIVE  
HEART  FAILURE

LV Dysfunction  causes Decreased  Blood  Pressure  and

Decreased  cardiac  output Decreased  Renal  perfusion

Stimulates  the  Release  

of  renin,  Which  allows  
conversion  of  
Angiotensin
to  Angiotensin  II.
Angiotensin  II  stimulates
Aldosterone secretion  which  
causes  retention  of  
Na+  and  Water,
increasing  filling  pressure
 CONCEPTUAL  CHF  MODELS:  
CHF  AS  A  NEUROHORMONAL DISORDER

Chronic  neurohormonal  activation Cytokines

Increased  retention Coronary  and  systemic Toxic  effects  of  angiotensin  II Oxidative
of  sodium  and  water vasoconstriction and  catecholamines stress

Increased  myocardial  oxygen  

Pulmonary   demand;;  reduced  myocardial  
Edema
congestion oxygen  supply

Hemodynamic Cardiac  myocyte

abnormalities dysfunction  and  necrosis

Progressive  impairment  of Cardiac  myocyte

cardiac  structure  and  function apoptosis

Disease  progression

Decreased  survival
 Role  of  Adrenergic  system  in  HF    
progression

Norepinefrine

a-adrenoreceptors b-adrenoreceptors

Miocardial remodeling
Myocite hypertrophy
LV contraction disorders
Myocite apoptosis

Myocardial insufficiency
 HAEMODYNAMIC  EFFECTS  OF  
UNOPPOSED  BETA  BLOCKADE

Unopposed  beta  blockade

Vasculature Heart

¯ Heart  rate
¯ Blood  pressure
­ Systemic  vascular  resistance
¯ Peripheral  blood  flow ¯ Myocardial  
¯ Substrate  utilisation oxygen  demand
 HF:  Neurohormonal regulation
Diuresis
Vasodilatation Antimitogenic

Natriuretic
Prostaglandins NO
Peptides

Myocardial  
ROS  – free  radicals  
Dysfunction Cytokines

Growth  
Vasopresin Renin Hormons
Endotelin
Angiotensin  II
Katecholamins
Apoptosis
Aldosteron
hypertrophy
Vasoconstriction  
Na  and  H2O
retension
 EXTRACELLULAR  MATRIX/CARDIAC  
INTERSTITIUM
• vScaffolding  to  support  myocytes  and  blood  vessels
• vLateral  connections  between  cells  and  muscle  bundles:  govern  
architecture  and  coordinate  force  delivery
• vTensile  strength  and  resilience  modulate  diastolic  stiffness,  
resist  deformation,  maintain  shape  and  thickness
MYOCITE “ SLIPPAGE ”

Changes  in  colagen  structure

­ LV  surface  area  (LV  weakness)

Adaptive  mechanisms  of  the  heart  
to  increased  load
• Frank  -­ Starling  mechanism

•  Ventricular  hypertrophy
– increased  mass  of  contractile  elements  ® ­strength
of  contraction  

• Increased  sympathetic  adrenergic  activity

– increased  HR,  increased  contractility

• Incresed  activity  of  R–A–A  system

 HEART FAILURE
ETIOLOGY  AND  
PATHOPHYSIOLOGY
• Compensatory  mechanisms-­ activated  to  maintain  adequate  CO
• Neurohormonal  responses:  Endothelin -­stimulated  by  ADH,  catecholamines,  and  
angiotensin  II  >

• Arterial  vasoconstriction
• Inc.  in  cardiac  contractility
• Hypertrophy  
 HEART  FAILURE
ETIOLOGY  AND  
PATHOPHYSIOLOGY
• Compensatory  mechanisms-­ activated  to  
maintain  adequate  CO
• Neurohormonal  responses: Proinflammatory  cytokines  
(e.g.,  tumor  necrosis  factor)  
• Released  by  cardiac  myocytes  in  response  to  cardiac  injury  
• Depress  cardiac  function  >  cardiac  hypertrophy,  contractile  
dysfunction,  and  myocyte  cell  death
 HEART  FAILURE
ETIOLOGY AND PATHOPHYSIOLOGY

• **Counter  regulatory  processes

• Natriuretic  peptides:  atrial  natriuretic  peptide  (ANP)  and  
b-­type  natriuretic  peptide (BNP)-­ *also  dx  test  for  HF

• Released  in  response  to  inc.  in  atrial  volume  and  ventricular  pressure
• Promote  venous  and  arterial  vasodilation,    reduce  preload  and  afterload  
• Prolonged  HF  >  depletion  of  these  factors
 BNP

• With  chronic  heart  failure,  atrial  mycotes  

secrete  increase  amounts  of  atrial  
natriuretic  peptide  (ANP)  and  brain  
natriuretic  pepetide  (BNP)  in  response  to  
high  atrial  and  ventricular  filling  pressures
• Usually  is  >  400  pg/mL  in  patients  with  
dyspnea  due  to  heart  failure.
 BNP  EFFECTS
VASODILATATION
KIDNEY
HAEMODYNAMIC
NATRIURESIS
Heart  index DIURESIS

Volemia
rhBNP R I SS Preload  
D S

Preload  
M
K
S
G Diuretics  
R
use
L
Afterload   G
F
C
G
R
R
H

C S S K V L
PVR   S P K MV
Q GS
G

Shortness  of  breath

Aldosteron
Endothelin
Norepinephrin
HEART  
No  increase  in  HR     SIMPATHETIC  AND  
No  proarhythmic  effect NEUROHORMONAL   SYSTEMS
 STAGES,  PHENOTYPES  AND  
TREATMENT  OF  HF
At Risk for Heart Failure Heart Failure

STAGE A STAGE B STAGE C

At high risk for HF but Structural heart disease Structural heart disease STAGE D
without structural heart but without signs or with prior or current Refractory HF
disease or symptoms of HF symptoms of HF symptoms of HF

e.g., Patients with:

• HTN
• Atherosclerotic disease
e.g., Patients with: e.g., Patients with:
• DM Refractory
• Previous MI e.g., Patients with:
• Obesity Development of symptoms of HF • Marked HF symptoms at
Structural heart • LV remodeling including • Known structural heart disease and
• Metabolic syndrome disease
symptoms of HF at rest, despite rest
LVH and low EF • HF signs and symptoms
or
• Asymptomatic valvular
GDMT • Recurrent hospitalizations
Patients despite GDMT
disease
• Using cardiotoxins
• With family history of
cardiomyopathy

HFpEF HFrEF

THERAPY THERAPY THERAPY THERAPY THERAPY

Goals Goals Goals Goals Goals
• Control symptoms • Control symptoms
• Heart healthy lifestyle • Prevent HF symptoms • Control symptoms • Patient education • Improve HRQOL
• Prevent vascular, • Prevent further cardiac • Improve HRQOL • Prevent hospitalization • Reduce hospital
coronary disease remodeling • Prevent hospitalization • Prevent mortality readmissions
• Prevent LV structural • Prevent mortality • Establish patient’s end-
abnormalities Drugs Drugs for routine use of-life goals
• ACEI or ARB as • Diuretics for fluid retention
Strategies • ACEI or ARB Options
Drugs appropriate • Identification of comorbidities • Beta blockers • Advanced care
• ACEI or ARB in • Beta blockers as
• Aldosterone antagonists measures
appropriate • Heart transplant
appropriate patients for Treatment
vascular disease or DM • Diuresis to relieve symptoms Drugs for use in selected patients • Chronic inotropes
In selected patients • Hydralazine/isosorbide dinitrate • Temporary or permanent
• Statins as appropriate of congestion
• ICD • ACEI and ARB MCS
• Revascularization or • Follow guideline driven • Digoxin • Experimental surgery or
valvular surgery as indications for comorbidities, drugs
appropriate e.g., HTN, AF, CAD, DM In selected patients • Palliative care and
• Revascularization or valvular • CRT hospice
• ICD • ICD deactivation
surgery as appropriate
• Revascularization or valvular
surgery as appropriate

You will use it in clinical practice