hf

1. Heart Failure: Pathophysiology
and Diagnosis
Dr. Priyanka Thakur
DM cardiology Resident

2. Definition
• The current American College of Cardiology
Foundation (ACCF)/American Heart Association
(AHA) guidelines define
• a complex clinical syndrome that results from
structural or functional impairment of
ventricular filling or ejection of blood, which in
turn leads to the cardinal clinical symptoms of
dyspnea and fatigue and signs of HF, namely
edema and rales.

3. Epidemiology
• Burgeoning problem worldwide, with >20 million people being affected.
• Overall prevalence of HF in the adult population in developed countries is
2%.
• HF prevalence follows an exponential pattern, rising with age, and affects
6–10% of people aged >65.
• Relative incidence of HF is lower in women than in men but women
constitute at least one-half the cases of HF because of their longer life
expectancy.
• Overall prevalence of HF is thought to be increasing, in part because
current therapies for cardiac disorders (e.g., myocardial infarction, valvular
heart disease, arrhythmias) are allowing patients to survive longer

4. PROGNOSIS
• Despite recent advances in the management of HF, the
development of symptomatic HF still carries a poor prognosis.
• 30–40% of patients die within 1 year of diagnosis and 60–
70% die within 5 years, mainly from worsening HF or as a
sudden event (probably because of a ventricular arrhythmia).
• Although it is difficult to predict prognosis in an individual,
patients with symptoms at rest (New York Heart Association
[NYHA] class IV) have a 30–70% annual mortality rate,
whereas patients with symptoms with moderate activity
(NYHA class II) have an annual mortality rate of 5–10%.

5. Terminology
• Heart failure with preserved, mid-range and
reduced ejection fraction.
• Related to the symptomatic severity of heart
failure-NYHA functional classification,
ACCF/AHA stages
• Related to location- Left heart, right heart,
combined

7. • Prevalence of HFpEF among patients with a discharge
diagnosis of HF increased from 38% to 54% from 1987–2001
• Increasing prevalence of HFpEF may be a consequence of
growing recognition, population aging and increases in
hypertension and obesity
• HFpEF and HFrEF have similar initial hospitalisation rates
and similar rehospitalisation rates.
• HFpEF and HFrEF have similarly high mortality. While
survival rates in HFpEF have not changed in recent years,
survival rates in HFrEF have improved.

8. Classification of Heart Failure
• The American College of Cardiology and
American Heart Association (ACC/AHA) HF
staging approach emphasizes the importance of
development and progression of disease.
• New York Heart Association (NYHA) functional
classification focuses more on exercise tolerance
in those with established HF.

10. ETIOLOGY
• Any condition that leads to an alteration in LV
structure or function can predispose a patient to
developing HF.
• Although the etiology of HF in patients with a
preserved EF differs from that of patients with
depressed EF, there is considerable overlap
between the etiologies of these two conditions.

13. • In 20–30% of the cases of HF with a depressed
EF, the exact etiologic basis is not known.
• These patients are referred to as having
nonischemic, dilated, or idiopathic
cardiomyopathy if the cause is unknown.

14. Pathogenesis

15. Heart Failure as a Progressive Model

17. Pathogenesis
• Compensatory neurohormonal Mechanisms
• Activation of countervailing vasodilatory
molecules-atrial and brain natriuretic peptides
(ANP and BNP), bradykinin, prostaglandins
(PGE2 and PGI2 ), and nitric oxide (NO)
• LV remodeling

18. Neurohormonal Mechanisms
activation of the adrenergic nervous systemic
system
Activation renin-angiotensin system (RAS)

19. • Responsible for
maintaining cardiac output through increased retention
of salt and water
peripheral arterial vasoconstriction and increased
contractility
and inflammatory mediators that are responsible for
cardiac repair and remodeling.
• Overexpression of these biologically active molecules
contributes to disease progression by virtue of the
deleterious effects these molecules exert on the heart and
circulation.

20. Activation of Sympathetic Nervous
System
• Decrease in cardiac output in HF.
• Accompanied by withdrawal of parasympathetic
tone.

24. •
Raised NE levels in HF
The circulating levels of NE in resting patients are two to three times than
normal persons.
Plasma levels of NE predict mortality in patients with HF.
In HF the coronary sinus NE concentration exceeds the arterial
concentration.

25. • .
Withdrawal of parasympathetic nerve stimulation
Decreased nitric oxide (NO) levels
Increased inflammation
Worsening LV remodeling
Several clinical trials with vagal nerve stimulation did not meet their primary
endpoint but have shown encouraging trends in several secondary endpoints

26. Activation of the Renin-Angiotensin
System
• mechanisms for RAS activation in HF include
renal hypoperfusion
decreased filtered sodium reaching the macula
densa in the distal tubule
increased sympathetic stimulation of the kidney,
leading to increased renin release from
juxtaglomerular apparatus

28. • AT1 receptor-
• vasoconstriction
• cell growth
• aldosterone secretion
• catecholamine release
• AT2 receptor-
• vasodilation
• inhibition of cell growth
• natriuresis
• bradykinin release

29. Aldosterone
• promotes the reabsorption of sodium in exchange
for potassium, in the distal segments of the
nephron.
• provokes endothelial cell dysfunction
• baroreceptor dysfunction
• inhibition of NE uptake

30. Angiotensin III
• stimulates the zona glomerulosa of the adrenal
glands to produce aldosterone
• vasopressin release in the brain
• modulate cardiac nervous sympathetic hyperactivity
• LV remodeling after MI.

31. Neurohormonal Alterations of Renal
Function
• One of the signatures of advancing HF is increased salt and water retention
by the kidneys.
• Concept of decreased effective arterial blood volume, which postulates that
despite blood volume expansion in HF, inadequate cardiac output sensed
by baroreceptors in the vascular tree leads to a series of compensatory
neurohormonal adaptations that resemble the homeostatic response to
acute blood loss
• Traditional theories
• “forward” failure, which attributes sodium retention to inadequate renal
perfusion as a consequence of impaired cardiac output, or
• “backward” failure, which emphasizes the importance of increased
venous pressure in favoring transudation of salt and water from the
intravascular to the extracellular compartment.

32. AVP
• Circulating AVP is elevated in many patients
with HF, even after correction for plasma
osmolality (i.e., nonosmotic release) and may
contribute to the hyponatremia that occurs in
HF.

33. V1a vasoconstriction, platelet aggregation, and
stimulation of myocardial growth factors
V1b adrenocorticotropic hormone (ACTH) secretion
from the anterior pituitary
V2 antidiuretic effects by stimulating adenyl cyclase
to increase the rate of insertion of water
channel−containing vesicles into the apical
membrane.

34. • The “vaptans,” vasopressin receptor antagonists
with V1a (relcovaptan) or V2 (tolvaptan,
lixivaptan) selectivity or nonselective V1a /V2
activity (conivaptan), have been shown to reduce
body weight and reduce hyponatremia in clinical
trials.

35. Counterregulatory neurohormonal
systems
• to offset the deleterious effects of the
vasoconstricting neurohormones.
• vasodilatory prostaglandins- (PGE2 ) and
prostacyclin (PGI 2)
• The natriuretic peptides

36. Natriuretic Peptides
• Atrial natriuretic peptide (ANP) and brain (B-type)
natriuretic peptide (BNP).
released in response to increases in atrial and
myocardial stretch
Increase excretion of sodium and water, while
inhibiting the release of renin and aldosterone
• ANP has a relatively short half-life of approximately
3 minutes, whereas BNP has a plasma half-life of
approximately 20 minutes.

37. • Natriuretic peptides are degraded by two major
mechanisms:
• NPR-C–mediated internalization, followed by
lysosomal degradation
• enzymatic degradation by neutral endopeptidase
(NEP) , (neprilysin)

39. • NEP inhibition of degradation of natriuretic
peptides results in vasorelaxation, natriuresis,
inhibition of hypertrophy, and fibrosis.
• Inhibition of degradation of other vasoactive
peptides, such as angiotensin II, angiotensin 1-7,
and ET, opposes the vasodilatory effects of
natriuretic peptides.

40. • The early use of omapatrilat, a dual vasopeptidase
inhibitor that inhibits both ACE and NEP, was not
shown to be more effective than ACE inhibition
alone in HF patients.
• Use of a combined AT1 receptor antagonist and a
neprilysin inhibitor (valsartan/sacubitril, LCZ696)
was shown to have a favorable impact on HF
outcome, including quality of life, exercise capacity,
and more importantly, HF hospitalization and total
mortality, in the PARADIGM-HF trial

41. Pathophysiologic mechanisms
underlying the development of HFpEF

43. LV remodeling

45. • Biologic stimuli for these changes are-
mechanical stretch of the myocyte
circulating neurohormones (e.g.
norepinephrine, angiotensin II)
inflammatory cytokines (e.g., tumor necrosis
factor [TNF])
growth factors (e.g., endothelin)
reactive oxygen species (e.g., superoxide).

46. Approach to the Patient
with Heart Failure

47. The Medical History and Physical
Examination

48. Medical History
Orthopnea, Paroxysmal nocturnal dyspnea
Edema (of extremities, scrotum, or elsewhere)
Shortness of breath at rest or during exercise
Fatigue
Diminished exercise capacity
Increasing abdominal girth or bloating Abdominal pain (particularly if
confined to right upper quadrant)
Cough, wheezing
Cheyne-Stokes respirations (often reported by family rather than patient)
Weight gain/weight loss
Loss of appetite or early satiety
Somnolence or diminished mental acuity

49. Historical Information Helpful in Determining if Symptoms Are
Caused by HF
A past history of HF
Cardiac disease (e.g., coronary artery disease, valvular or congenital disease,
previous myocardial infarction)
Risk factors for heart failure (e.g., diabetes, hypertension, obesity)
Systemic illnesses that can involve the heart (e.g., amyloidosis, sarcoidosis,
inherited neuromuscular diseases)
Recent viral illness or history of HIV infection or Chagas disease
Environmental and/or medical exposure to cardiotoxic substances , any
Substance abuse
Family history of HF or sudden cardiac death
Noncardiac illnesses that could affect the heart indirectly, including high-output
states (e.g., anemia, hyperthyroidism, arteriovenous fistulas)

50. Physical Examination
Elevated jugular venous pressure , hepatojuglar reflex
Third heart sound (gallop rhythm), Laterally displaced apical impulse
Tachypnea
Cool and/or mottled extremities*
Tachycardia
Extra beats or irregular rhythm
Narrow pulse pressure or thready pulse* Pulses alternans
Dullness and diminished breath sounds at one or both lung bases Rales,
rhonchi, and/or wheezes
Tricuspid or mitral regurgitant murmur
Hepatomegaly (often accompanied by right upper quadrant discomfort)
* Ascites Presacral edema Anasarca* Pedal edema, chronic venous stasis
changes

52. • Assessment for systemic congestion taken
together with evaluation for reduced cardiac
output may be useful to categorize patients into
“dry/warm” (uncongested with normal
perfusion), “wet/warm”

54. Routine Laboratory Assessment
• Chest Radiography
• “butterfly” pattern of interstitial and alveolar opacities bilaterally
fanning out to the periphery of the lungs.
• Kerley B lines (thin horizontal linear opacities extending to the
pleural surface caused by accumulation of fluid in the interstitial
space)
• peribronchial cuffing, and evidence of prominent upper lobe
vasculature (indicating pulmonary venous hypertension) are the
most prominent findings.
• Pleural effusions and fluid in the right minor fissure may also be
seen.

56. ECG
• HF patients the ECG is can be normal.
• Can provide a clue to etiology.

57. Biomarkers

58. Natriuretic Peptides
• useful biomarkers for HF diagnosis, estimation
of HF severity and prognosis, and possibly for
management of HF as well
• B-type natriuretic peptide (BNP) and its amino-
terminal (N-terminal) cleavage propeptide
equivalent, NTproBNP are most commonly
measured.

59. • Because of the differences in their clearance,
BNP and NT-proBNP have considerably
different halflives (BNP: 20 minutes; NT-
proBNP: 90 minutes), and thus they circulate
with very different concentrations

60. • Pivotal data for BNP and NT-proBNP testing to
diagnose acute HF came from the Breathing Not
Properly study and the ProBNP Investigation of
Dyspnea in the Emergency Department (PRIDE)
study, respectively
• the International Collaborative of NT-proBNP
(ICON) investigators subsequently showed that
age stratification improved PPV of NTproBNP in
acutely dyspneic patients

62. Raised Natriuretic Peptides
valvular heart disease
pulmonary hypertension
ischemic heart disease
atrial arrhythmias
constrictive pericarditis
Old age
renal failure
hyperdynamic states, including sepsis
angiotensin receptor neprilysin inhibitors

63. Soluble concentrations of ST2
• strongly linked to progressive HF and death in patients across
the four ACC/AHA stages of HF.
• pivotal role in the formation of fibrosis in the heart
• elevated concentrations are associated with progressive
cardiovascular dysfunction, remodeling, and risk of death.
• concentrations are additive to natriuretic peptides for
prognostication, are useful in both HFrEF and HFpEF
• concentrations are dynamic i.e. changes after HF therapies.

64. • Notably ST2 values predicted future HF, beyond
other biomarkers such as BNP as well as
echocardiographic parameters.
• also indicate vascular remodeling and may
therefore predict future arterial hypertension.

65. Galectin 3
• novel biomarker of tissue fibrosis
• produced by activated macrophages involved in
response to tissue injury and is strongly associated
with increased myocardial collagen formation.
• elevated galectin 3 values not only predict adverse
outcomes in HF patients with both HFrEF and
HFpEF, but also predict onset of HF in apparently
normal patients, similar to ST2.

66. Other Novel Biomarkers
• Midregional fragment of proadrenomedullin
• Growth differentiation factor-15
• The C-terminal fragment of provasopressin (also
known as copeptin)

67. Exercise Testing
• Treadmill or bicycle exercise testing is not
routinely advocated for patients with HF, but
either is useful for assessing the need for cardiac
transplantation in patients with advanced HF
• A peak oxygen uptake (vo2) < 14 ml/kg per min
is associated with a relatively poor prognosis and
have been shown, in general, to have better
survival when transplanted than when treated
medically.

68. Imaging techniques

69. Echocardiography
• can provide a semiquantitative assessment of LV size
and function as well as the presence or absence of
valvular and/or regional wall motion abnormalities
(indicative of a prior MI).
• left atrial dilation and LV hypertrophy, together with
abnormalities of LV diastolic filling provided by pulse-
wave and tissue Doppler, is useful for the assessment of
HF with a preserved EF.
• assessing RV size and pulmonary pressures, which are
critical in the evaluation and management of cor
pulmonale

70. Magnetic resonance imaging (MRI)
• comprehensive analysis of cardiac anatomy and
function and is now the gold standard for
assessing LV mass and volumes.
• assessing LV structure and for determining the
cause of HF (e.g., amyloidosis, ischemic
cardiomyopathy, hemochromatosis).

71. Nuclear Imaging
• SPECT and PET technologies are well suited for
assessing myocardial ischemia and viability and for
evaluating myocardial function.
• Fluorine-18 fluorodeoxyglucose ( 18F-FDG) –a
characteristic heterogeneous uptake pattern in the
myocardium may be seen in patients with cardiac
sarcoidosis, in contrast to diffuse uptake seen in
dilated cardiomyopathy and normal individuals
• Technetium-99m pyrophosphate ( 99mTcPYP)-
transthyretin (TTR) amyloidosis.

72. Genetic testing in heart failure
• Molecular genetic analysis in patients with
cardiomyopathies is recommended when the
prevalence of detectable mutations is sufficiently
high and consistent to justify routine targeted
genetic screening.
• Genetic counselling is recommended in patients
with HCM, idiopathic DCM and ARVC.