SLIDES PREPARED FOR PG TEACHING PROGRAMME ,HARRISONS AND BRAUNWALD AS SOURCE HOPE IT HELPS OTHERS

1. HEART FAILURE
PRESENTOR
DR SHANKARAGOUDA PATIL
M.D (GEN MED)
JJMMC DAVANGERE

2. Definition
• Heart failure (HF) is a clinical syndrome that occurs in
patients who, because of an inherited or acquired
abnormality of cardiac structure and/or function, develop a
constellation of clinical symptoms (dyspnea and fatigue)
and signs (edema and rales) that lead to frequent
hospitalizations, a poor quality of life, and a shortened life
expectancy.

3. Epidemiology
• more than 20 million people affected
• The overall prevalence of HF in the adult population in
developed countries is 2%
• rising with age, and affects 6–10% of people over age 65
• The overall prevalence of HF is thought to be increasing,
in part because current therapies for cardiac disorders,
such as myocardial infarction (MI), valvular heart disease,
and arrhythmias, are allowing patients to survive longer.

4. TYPES
(1) HF with a depressed EF (commonly referred to as
systolic failure) or
• (2) HF with a preserved EF (commonly referred to as
diastolic failure).

7. Prognosis
• the development of symptomatic HF still carries a poor
prognosis.
• Community-based studies indicate that 30–40% of
patients die within 1 year of diagnosis and 60–70% die
within 5 years
• 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%.

14. Basic Mechanisms of Heart Failure
Systolic Dysfunction
• LV remodeling
• (1) myocyte hypertrophy,
• (2) alterations in the contractile properties of the myocyte,
• (3) progressive loss of myocytes through necrosis,
apoptosis, and autophagic cell death
• (4) adrenergic desensitization
• (5) abnormal myocardial energetics and metabolism
• (6) reorganization of the extracellular matrix with
dissolution of the organized structural collagen weave
surrounding myocytes and subsequent replacement by an
interstitial collagen matrix that does not provide structural
support to the myocytes.

16. Diastolic Dysfunction
• Myocardial relaxation is (ATP)-dependent process that is
regulated by uptake of cytoplasmic calcium into the SR by
SERCA2A -
• reductions in ATP concentration, as occurs in ischemia, may
interfere with these processes and lead to slowed myocardial
relaxation. Alternatively, if LV filling is delayed because LV
compliance is reduced LV filling pressures will similarly remain
elevated at end diastole .
• In addition to impaired myocardial relaxation, increased
myocardial stiffness secondary to cardiac hypertrophy and
increased myocardial collagen content may contribute to
diastolic failure.
• Importantly, diastolic dysfunction can occur alone or in
combination with systolic dysfunction in patients with HF.

17. Left Ventricular Remodeling
• the changes in LV mass, volume, and shape and the
composition of the heart . increase in LV end-diastolic
volume, LV wall thinning occurs as the left ventricle begins to
dilate. The increase in wall thinning, along with the increase in
afterload created by LV dilation, leads to a functional afterload
mismatch
• Moreover, the high end-diastolic wall stress might be expected
to lead to
• (1) hypoperfusion of the subendocardium
• (2) increased oxidative stress
• (3) sustained expression of stretch-activated genes
, hypertrophic signaling pathways.
• Increasing LV dilation also results in tethering of the papillary
muscles with resulting functional mitral regurgitation

20. central sleep apnoea

22. Diagnosis
• Routine Laboratory Testing ; complete blood count, a
panel of electrolytes, blood urea nitrogen, serum
creatinine, hepatic enzymes, and a urinalysis.
• Electrocardiogram (ECG)
• Chest X-Ray
• Biomarkers
• Assessment of Lv Function

23. Biomarkers

24. natriuretic peptide
• Both B-type natriuretic peptide (BNP) and N-terminal pro-
BNP, are relatively sensitive markers for the presence of
HF with depressed EF; they also are elevated in HF
patients with a preserved EF, albeit to a lesser degree.
• However, it is important to recognize that natriuretic
peptide levels increase with age and renal impairment,
are more elevated in women, and can be elevated in right
HF from any cause.
• Levels can be falsely low in obese patients and may
normalize in some patients after appropriate treatment.
• Other biomarkers, such as troponin T and I, C-reactive
protein, TNF receptors, and uric acid, may be elevated in
HF and provide important prognostic information.

25. Assessment of Lv Function

27. Echocardiography
• Transthoracic echocardiography can be performed
without risk to the patient, does not involve radiation
exposure, and can be performed at the bedside if
necessary. It is particularly well suited for evaluating the
structure and function of both the myocardium and heart
valves and providing information about intracardiac
pressures and flows. Echocardiography may be limited in
some patients because available imaging planes and
image quality depend on acoustic windows, which may be
suboptimal as a result of obesity, emphysema, or other
causes

28. Diagnosis and Management of Acute
Heart Failure Syndromes
AHFS can be defined as the new onset or recurrence of
gradually or rapidly developing symptoms and signs of HF
requiring urgent or emergent therapy and resulting in
hospitalization.
• (1) stabilize the hemodynamic derangements that
provoked the symptoms
• (2) identify and treat the reversible factors that
precipitated decompensation, and
• (3) reestablish an effective outpatient medical regimen
that will prevent disease progression and relapse.

36. Vasodilators
• By stimulating guanylyl cyclase within smooth-muscle
cells, nitroglycerin, nitroprusside, and nesiritide exert dilating
effects on arterial resistance and venous capacitance
vessels, results in a lowering of LV filling pressure, a
reduction in mr, and improved forward co without increasing
hr or causing arrhythmias

37. Inotropic Agents
• direct hemodynamic benefits by stimulating cardiac
contractility as well as by producing peripheral
vasodilation. Collectively, these hemodynamic effects
result in an improvement in cardiac output and a fall in LV
filling pressures
• short-term use provides hemodynamic benefits in
cardiogenic shock ,but these agents are more prone to
cause tachyarrhythmias and ischemic events .
• If patients require sustained use of intravenous
inotropes, strong consideration should be given to the use
of an ICD to safeguard against the proarrhythmic effects of
these agents.

38. Dobutamine and Milrinone
• Dobutamine, exerts its effects by stimulating beta 1 and beta 2
receptors, with little effect on alpha1 receptors. Dobutamine is
given as a continuous infusion at an initial infusion rate of 1–2
mic g/kg per min. Higher doses (>5 micr g/kg per min) are
frequently necessary for severe hypoperfusion; however, there
is little added benefit to increasing the dose above 10 micro
g/kg per min.
• Milrinone is a phosphodiesterase III inhibitor that leads to
increases cAMP . Milrinone may act synergistically with -
adrenergic agonists to achieve a greater increase in cardiac
output , If the patient has a low bp, omit the bolus dose.
Because milrinone is a more effective vasodilator than
dobutamine, it produces a greater reduction in LV filling
pressures, with a greater risk of hypotension.

39. Levosimendan
• Levosimendan is a calcium sensitizer and ATP-dependent
potassium channel opener that has positive inotropic and
vasodilatory effect.
• an improvement in patient self-assessment, a decrease in
levels of BNP, and a shorter hospital stay were noted in
patients admitted with HF and reduced ejection fraction
• According to the ESC guidelines, levosimendan should be
considered for patients with low cardiac output states
despite the use of other therapies. Levosimendan should
be started with a bolus dose (3 to 12 mg/kg) during 10
minutes, unless SBP <100 mm Hg, followed by a
continuous infusion (0.05 to 0.2 mg/kg/min for 24 hours

40. Vasoconstrictors

41. Vasopressin Antagonists
• three types of receptors, V1a, V1b, and V2. Selective V1a
antagonists block the vasoconstricting effects of AVP in
peripheral vascular smooth muscle cells, whereas V2
selective receptor antagonists inhibit recruitment of
aquaporin channels in collecting duct
• Combined V1a/V2 antagonists lead to a decrease in
systemic vascular resistance and prevent the dilutional
hyponatremia that occurs in HF patients
• All four AVP antagonists increase urine volume, decrease
urine osmolarity, and have no effect on 24-hour sodium
excretion

42. Vasopressin Antagonists

43. Management of chronic Heart Failure
Patients with Reduced Ejection Fraction

47. TREATMENT
• Activity-routine modest exercise has been shown to be
beneficial in patients with NYHA class I–III HF.
• Diet-Dietary restriction of sodium (2–3 g daily) is
recommended in all patients with HF and preserved or
depressed EF. Further restriction (<2 g daily) may be
considered in moderate to severe HF. Fluid restriction is
generally unnecessary unless the patient develops
hyponatremia (<130 meq/L)
• Caloric supplementation is recommended for patients with
advanced HF and unintentional weight loss or muscle
wasting (cardiac cachexia);

50. Diuretics

52. • Many of the clinical manifestations of moderate to severe
HF result from excessive salt and water retention that
leads to volume expansion and congestive symptoms.
• Diuretics are the only pharmacologic agents that can
adequately control fluid retention in advanced HF and
they should be used to restore and maintain normal
volume status in patients with congestive symptoms or
signs of elevated filling pressures
• Se-electrolyte and volume depletion as well as worsening
azotemia

53. Diuretic Resistance and Management
• resistant to diuretic drugs when moderate doses of a loop
diuretic do not achieve the desired reduction of the extracellular
fluid volume
• braking phenomenon
• the potential delay in their rate of absorption
• postdiuretic NaCl retention
• loss of renal responsiveness to endogenous natriuretic
peptides as HF advances
• diuretics increase solute delivery to distal segments of the
nephron, causing epithelial cells to undergo hypertrophy and
hyperplasia
• treating the diuretic-resistant patient is to administer two
classes of diuretic concurrently
• metolazone because its half-life is longer and remain
effective even when the gfr is low

54. Prevention of disease progression

55. ACE Inhibitors
• used in symptomatic and asymptomatic patients with a reduced
EF <40%
• ACEIs interfere with the RAS by inhibiting the enzyme that is
responsible for the conversion of angiotensin I to angiotensin II
• the upregulation of bradykinin
• ACEIs stabilize LV remodeling, improve patient
symptoms, prevent hospitalization, and prolong life
• Abrupt withdrawal avoided in the absence of life-threatening
complications (e.g., angioedema, hyperkalemia).
• Side eff;-decreases in blood pressure , mild azotemia
, nonproductive cough (10% to 15% of patients) and
angioedema (1% of patients). hyperkalemia
• who cannot tolerate ACEIs because of cough or
angioedema, ARBs are the next recommended

56. Angiotensin Receptor Blockers
• symptomatic and asymptomatic patients with an EF less
than 40% who are ACE-intolerant for reasons other than
hyperkalemia or renal insufficiency
• ARBs block the effects of angiotensin II on the
angiotensin type 1 receptor, the receptor subtype
responsible for almost all the adverse biologic effects
relevant to angiotensin II on cardiac remodeling
• hypotension, azotemia, and hyperkalemia

57. Beta-Adrenergic Receptor Blockers
• interfere with the harmful effects of sustained activation of
the nervous system by competitively antagonizing one or
more adrenergic receptors
• most of the deleterious effects mediated by the beta1
receptor
• When given in concert with ACEIs, beta blockers reverse
the process of LV remodeling, improve patient
symptoms, prevent hospitalization, and prolong life
• beta blocker therapy is well tolerated by the great majority
of HF patients (>85%), including patients with comorbid
conditions such as dm, copd, and pvd

59. Renin Inhibitors
• Aliskiren is an orally active renin inhibitor that appears to
suppress RAS to a similar degree as ACE-inhibitors
• Aliskiren is a nonpeptide inhibitor that binds to the active
site of renin, preventing the conversion of
angiotensinogen to angiotensin I

60. Management of Patients WHO Remain
Symptomatic
• Digoxin is recommended for patients with symptomatic LV
systolic dysfunction with atrial fibrillation, and
• for patients who have signs or symptoms of HF while
receiving standard therapy, including ACE inhibitors and
beta blockers.
• Therapy with digoxin is commonly initiated and
maintained at a dose of 0.125–0.25 mg daily. For the
great majority of patients
• the dose should be 0.125 mg daily, and the serum digoxin
level should be <1 ng/mL

61. Cardiac Glycosides
• Digoxin exerts its effects by inhibiting the Na+,K+-ATPase
pump. leads to an increase in intracellular calcium and
hence increased cardiac contractility
• However, the more likely mechanism of digoxin in HF
patients is to sensitize Na+,K+-ATPase activity in vagal
afferent nerves, that counterbalances the increased
activation of the adrenergic system in advanced HF.
• Digoxin also inhibits Na+,K+-ATPase activity in the kidney
and may therefore blunt renal tubular resorption of
sodium.
•

62. Complications of Digoxin Use
• (1) cardiac arrhythmias, including heart block (especially in
older patients) and ectopic and reentrant cardiac rhythms;
• (2) neurologic complaints such as visual disturbances,
disorientation, and confusion; and
• (3) gastrointestinal symptoms such as anorexia, nausea, and
vomiting
• Oral potassium administration is often useful for atrial, AV
junctional, or ventricular ectopic rhythms, even when the serum
potassium level is in the normal range, unless high-grade AV
block is also present
• Potentially life-threatening digoxin toxicity can be reversed by
antidigoxin immunotherapy using purified Fab fragments

63. Anticoagulation and Antiplatelet Therapy
• Patients with HF have an increased risk for arterial or venous
thromboembolic events.
• In clinical HF trials, the rate of stroke ranges from 1.3 to 2.4%
per year
• Treatment with warfarin [goal (INR) 2–3] is recommended for
patients with HF and chronic or paroxysmal afor with a history
of systemic or pulmonary emboli, including stroke or tia.
• Patients with symptomatic or asymptomatic ischemic
cardiomyopathy and documented recent large anterior MI or
recent MI with documented LV thrombus should be treated with
warfarin (goal INR 2–3) for the initial 3 months after the MI
unless there are contraindications to its use

64. Management of HF with a Preserved
Ejection Fraction (>40–50%)
• no proven therapy
• initial treatment efforts should be focused, wherever
possible, on the underlying disease process (e.g.,
myocardial ischemia, hypertension) .
• Precipitating factors such as tachycardia and af should
be treated . Dyspnea may be treated by reducing total
blood volume (dietary sodium restriction and diuretics),
decreasing central blood volume (nitrates), or blunting
neurohormonal activation with ACE inhibitors, ARBs,
and/or beta blockers.
• Treatment with diuretics and nitrates should be initiated at
low doses to avoid hypotension and fatigue

65. Potential New Therapies
• Soluble Guanylate Cyclase Activators-Cinaciguat
• Chimeric Natriuretic Peptides
• Direct Renin Inhibitor
• Adenosine Antagonists
• Ularitide
• Endothelin Antagonists
• Cardiac Myosin Activators
• Istaroxime
• Stresscopin
• Relaxin

66. Emerging Therapies and Strategies in the
Treatment of Heart Failure
• Stem and Progenitor Cells
• Gene Therapy

67. Gene Therapy

68. Myocardial Stem and Progenitor Cells
Repair and Regeneration

70. Pharmacogenetics
• pharmacogenetics attempts to define common gene
polymorphisms, or sets of polymorphisms, that underlie
variability in drug action.
• Given the tremendous heterogeneity that exists in HF
patients, it is likely that genetic variations play a significant
role in determining drug metabolism, disposition, and
functional activity in HF patients

71. Metabolic Modulation
• The prototype partial inhibitors of fatty acid oxidation
(pFOX), etomoxir, oxfenicine, and perhexiline, act by
inhibiting carnitine palmitoyltransferase I (CPT I), the
gatekeeper of fatty acid entry to the mitochondrion
, These agents shift energy use from free fatty acids to
glucose by decreasing oxidation of free fatty acids.

73. Ranolazine (Ranexa)
• Ranolazine (Ranexa) is a novel anti-ischemic drug that
prolongs the QT interval and is the first pFOX inhibitor
approved by the Food and Drug Administration for the
treatment of angina.
• the antianginal effects of ranolazine may be related to
decreased sodium entry into cells by inhibition of the rapid
component of the delayed rectifier K+ current, IKr
• Ranolazine also increases the activity of pyruvate
decarboxylase, a key regulator of glucose metabolism,
most likely because of loss of inhibition of the end
products of the beta-oxidation (NADH, acetyl-CoA)

74. Device Therapies in Chronic Systolic
Heart Failure
• This includes
• cardiac resynchronization therapy (CRT) devices,
• ICDs, implantable cardiac defibrillators
• LV assist devices (LVADs).

75. Implantable Cardioverter Defibrillators
• ICD as primary prevention of all-cause mortality in well-
treated NYHA Class II and III patients with LVEFs of less
than or equal to 30 percent There is generally a weaker
recommendation for such patients with EFs of 31 to 35
percent.
• unless they have a poor chance of survival related to
some comorbidity or a contraindication to the implantation
or use of this device.
• Implantable cardioverter defibrillators are also strongly
recommended in patients with hemodynamically
destabilizing vt, vf, and resuscitated cardiac arrest, for the
secondary prevention of mortality.

76. Cardiac Resynchronization Therapy
• Biventricular pacing is accomplished through
simultaneous pacing of both the left and right
ventricles, with standard right sided transvenous lead
placement as in dual-chamber and defibrillator lead
implantation
• CRT for patients with LVEFs less than or equal to 35
percent, normal sinus rhythm, and NYHA functional Class
III or ambulatory Class IV symptoms despite
recommended optimal medical therapy, who have
ventricular dyssynchrony, unless contraindicated.
• Currently, guidelines define ventricular dyssynchrony as a
QRS duration of at least 120 msec.

77. Surgeries
• Cardiac Transplantation
• Mitral Valve Procedures
• Ventricular Restoration/Remodeling
• Cardiac Support Devices
• Ventricular Assist Devices

78. Cardiac Transplantation

80. Ventricular Assist Devices

81. INDICATIONS
• 1.Decompansated end stage chronic heart failure
• 2.Acute refractory cardiogenic shock
• Long term devices are preferred for chf
• Short term devices for acute refractory cardiogenic shock
• Other consideration includes need for biventricular
support,cost.device related risks,patient characteristics

82. SUMMARY
• The severity of clinical presentation of AHFS does not always
correlate with long-term outcomes
• LV dysfunction and its progression are the main cause of the
high rehospitalization rates and of the mortality observed in HF
• Hemodynamic improvement should result from amelioration of
myocardial dysfunction rather than from myocardial stimulation
that may result in myocardial injury
• Viable but dysfunctional myocardium, which may potentially be
salvageable, is presumably present in a number of patients
with AHFS and may represent an important target for therapy.
• Myocardial or kidney injury may occur during an episode of
AHF and may contribute to the progression of HF.
•

83. THANK YOU