The document provides information on the pharmacotherapy of heart failure, including: - Heart failure results from the heart's inability to pump sufficient blood due to problems with structure or function. - It discusses the causes, pathophysiology, classification, clinical manifestations, diagnosis, and treatment of heart failure. - Treatment involves managing symptoms, improving cardiac function, and slowing disease progression through medications, lifestyle changes, and procedures. The goal is to improve quality of life and survival.

1. 1
Pharmacotherapy of Heart Failure
BY
Abreham D

2. Outline
• Introduction
• Etiology/ cause
• Pathophysiology
• Manifestations
• Diagnosis
• Treatment
• Out come evaluation
2

3. Terminologies
• Preload
• Afterload
• Dystolic HF
• Systolic HF
• Myocardial infarction
• Stroke Volume
• Cardiac out put
• Ejection Fraction
• End diastolic Volume
• Cardiac remodeling
3

4. Introduction
• Heart failure (HF) is a complex, progressive disorder in which
the heart is unable to pump sufficient blood to meet the needs of
the body.
 Low COP and inadequate oxygen to the rest body
• A progressive clinical syndrome that can result from any
abnormality in cardiac structure or function
Impairs the ability of the ventricle to fill with or eject blood.
4

5. Heart failure
• HF may be caused by an abnormality in:
 Systolic function
 Diastolic function, or both
• Making the distinction is important because the treatment
of HF may be quite different
5

6. Cont..
• HF with reduced systolic function (i.e, reduced LVEF)
is the classic, more familiar form of the disorder
• Current up to 50% of patients with HF have preserved
left ventricular systolic function with presumed
diastolic dysfunction
Termed heart failure with preserved ejection
fraction (HFpEF). EF >50%
Referred to as heart failure with reduced ejection
fraction (HFrEF). <40% EF
6

7. Epidemiology
• World wide prevalence  23 million people affected
• Every year, 870,000 people have a new diagnosis of HF
• Nearly 6 million in Americans with HF
• After age 65, HF incidence approaches 10 per 1,000 person-
years
• A large majority of patients with HF are elderly, with multiple
comorbid conditions that influence morbidity and mortality.
7

8. Classification of HF
Diastolic HF
• ed ventricular filling
• But normal contraction
• Increase Preload
pressure
• Relieved with Vasodilators
Systolic HF
• ed ventricular
contraction
reduced COP
• Reduced ejection Fraction
8

9. Diastolic & systolic HF
9

10. 10

11. Classification
Acute HF
• A  in COP suddenly
• Has no EDEMA
• Hypotension
• May be caused by
sudden MI
Chronic HF
• Progressive/late HF
• Often has EDEMA
• May be caused by
Progressive MI/
cardiomyopathy
11

12. Classification …
Right sided HF
• Problem on right
ventricle
• Leads to back flow of
blood right atrium
 peripheral congestion
Left sided HF
• Leads to back flow of
blood to left atrium 
pulmonary vein Edema
and congestion
• Most common
12

13. 13
Clinical Manifestations
• Tachycardia and irregular
• Dyspnea
• Peripheral and pulmonary
edema
• Cardiomegaly
• Distention of jugular veins
• The primary signs and symptoms:
• Edema in leg and feet
• Cough
• Abdominal swelling (ascites)
• Weight gain
• Decreased exercise tolerance
(fatigue)

14. Cause of HF
• Underlying causes of HF include:
 Arteriosclerotic heart disease
 Myocardial infarction
 Hypertension
 Valvular heart disease
 Dilated cardiomyopathy
MI leads to reduction in muscle mass
due to death of affected myocardial cells.
Coronary artery disease
the most common cause of
HFrEF, ~ 70% of cases
14

15. Causes of SHF & DHF
Systolic dysfunction (decreased contractility)
• Reduction in muscle mass (e.g, myocardial infarction)
• Dilated cardiomyopathies
• Ventricular hypertrophy
 Pressure overload (e.g, systemic or pulmonary hypertension,
aortic or pulmonic valve stenosis)
 Volume overload (e.g, valvular regurgitation, shunts, high-
output states)
15

16. Cause Cont..
Diastolic dysfunction (restriction in ventricular filling)
• Increased ventricular stiffness
 Ventricular hypertrophy (eg, hypertrophic cardiomyopathy)
 Infiltrative myocardial diseases (eg, amyloidosis,
sarcoidosis, endomyocardial fibrosis)
 Myocardial ischemia and infarction
• Mitral or tricuspid valve stenosis
• Pericardial disease (eg, pericarditis, pericardial tamponade)
16

17. Pathophysiology
Cardiac output is determined by
• Preload (the volume and pressure of blood in the ventricles at
the end of diastole),
• Afterload (the volume and pressure of blood in the ventricles
during systole) and
• Myocardial contractility
17
This is the basis of Frank Starling’s Law
ed preload ( adaptive)  stretching of sarcomeres→ ed contractility→ ed CO
Excessive and Continual of the adaptive mechanism
ed preload  excessive stretch→ ed contraction→ ed SV/CO

18. Cont….
• To attempt to maintain cardiac output (CO),
the surviving myocardium undergoes a
compensatory remodeling
– Thus beginning the maladaptive process that
initiates the HF syndrome and leads to further
injury to the heart
18

19. Cntd…..
• Lack of contractile force  ed ventricular function
 ed CO
• As a result a variety of adaptive mechanisms are
activated:
1. Extrinsic (neuro-humoral) compensatory mechanisms
2. Intrinsic (cardiac) compensatory
19

20. 20

21. Cardiac Failure
 sympathetic
activity
 Renal perfusion
Renin  Ang I Ang II
Aldosterone
 Na & water retention
 Capillary
filtration
Edema
 Venous pressure
 Bp
 COP
21

22. 22

23. Factors Precipitating/Exacerbating Heart Failure
Drugs like
• Negative Inotropic Effect– (Beta-blockers, diltiazem)
• Cardiotoxic– Doxorubicin, Cyclophosphamide
• Sodium and Water Retention– NSAIDs,
Glucocorticoids
• Sodium-containing drugs--carbenicillin disodium
23

24. Diagnosis
Framingham criteria for Clinical Dx of HF
Major
• Orthopenea
• Riase JVP
• Rales
• S3 gallob
• CxR cardiomegally
• CXR plueral edema
24
Minor
• Pheripheral edema
• Night cough
• Hepatomegallly
• Plueral effusion
• HR>120 bt/min
Validated HF  2 major OR
 1 major + 2 minor

25. Diagnosis ….
• The patient’s volume status should be documented by assessing
– The body weight, JVD, and Presence or absence of pulmonary congestion and
peripheral edema.
• Laboratory testing may assist in identification of disorders that cause or
worsen HF
• The initial evaluation should include:
 Complete blood count,
 Serum electrolytes (including calcium and magnesium),
 OFT  renal and hepatic function,
 Urinalysis, lipid profile, hemoglobin A1C
 Thyroid function tests
 Chest x-ray, and 12-lead ECG
25

26. Classification of HF severity
• Based on Physical examination + diagnostic tests
 Functional and stage
26

27. NYHA Functional Classification
Class Description of Patients with cardiac disease
Class I Without limitations of physical activity. Ordinary physical activity
does not cause undue fatigue, dyspnea, or palpitation.
Class II Slight limitations of physical activity. Ordinary physical activity
results in fatigue, palpitation, dyspnea, or angina.
Class III Marked limitation of physical activity. Although patients are
comfortable at rest, less than ordinary activity will lead to
symptoms.
Class IV An inability to carry on physical activity without discomfort.
Symptoms of congestive heart failure are present even at rest. With
any physical activity, increased discomfort is experienced. 27
Symptom Vs Activity

28. ACCF/AHA Stage classification of HF
28
Structural Damage

29. Stage and class
29

30. Treatment
Desired Outcomes
• Improve the patient’s quality of life,
• Relieve or reduce symptoms,
• Prevent or minimize hospitalizations,
• Slow progression of the disease, and
• Prolong survival
30

31. General approach
• The 1st step of mgt of CHF is to determine the
etiology or precipitating factors.
– Treatment of underlying disorders (like hyperthyroidism) may
obviate the need for treating HF.
• Treatment of Congestion
• Cardiac function can be improved by
 Increasing contractility
 Optimizing preload or decreasing afterload
31

32. Non-pharmacological
• Cardiac rehabilitation
• Surgical intervention
• Cardiac resynchronization
• Cardioverter-defibrillator
• Restriction of fluid intake (≤ 2 L/day from all
sources) and dietary sodium (<2–3 g of
sodium/day).
32

33. Pharmacological
• Diuretics
• ACEI/ARBs
• BBs
• Digitalis
• Vasodilators
• CCBs
33

34. Order of therapy
• Loop diuretics are introduced 1st to reduce sign & symptoms
• ACE inhibitors, or if not tolerated, angiotensin II receptor blockers (ARBs)
– Drugs are usually started at low doses and then titrated to goals
 Gradually increased at 1-2 week interval
 2.5 mg of enalapril BID, Max of 20 mg BID
 6.25 mg of captopril TID , max 50 mg TID
 5 mg of lisinopril / daily or up to 40 mg/day
 1-2 wks of change/starting in dose asses K+ and renal function
• Beta blockers are initiated after the patient is stable on ACE inhibitors, again
beginning at low doses with titration to trial goals as tolerated.
34

35. 35

36. Treatment of Stage A Heart Failure
• Stage A do not have structural heart disease or HF
symptoms but are at high risk for developing HF
because of the presence of risk factors
• Risk factor identification
Modification to prevent the development of structural
heart disease and subsequent HF is emphasized
36
Focusing on the treatment of those risk
factors can reduce HF progression

37. Commonly encountered risk factors
• HTN
• Dyslipidemia
• Diabetes
• Obesity
• Metabolic syndrome
• Smoking, and
• Coronary artery disease
37
ACE inhibitors or ARBs and
statins are recommended for HF
prevention of vascular risks
Treating the risk factors

38. Treatment of Stage B Heart Failure
• Stage B have structural heart disease, but do not have HF
symptoms
• Treatment is targeted at minimizing additional injury and
preventing or slowing the remodeling process
• ACE inhibitors or ARBs and β-blockers are important
components of therapy + preventing risk factors
38

39. Treatment of Stage C HF
• Patients with structural heart disease and previous or current
symptoms are classified in Stage C and include both HFrEF
and HFpEF.
• ACE inhibitor or ARB and an evidence-based β-
blocker
• Loop diuretics, aldosterone antagonists, digoxin and
hydralazine–isosorbide dinitrate are advantageous
39

40. 40

41. Treatment of Stage D HF
• Often referred to as advanced, refractory, or end-stage HF.
• Stage D HF includes patients receiving maximally tolerated
GDMT that have persistent symptoms
• These patients often:
 Undergo recurrent hospitalizations
 Cannot be discharged from the hospital without special
interventions
 Have a poor quality of life,
 Are at high risk for morbidity and mortality.
41

42. Cont...
• Continuous IV positive inotropic therapy
• Specialized therapies including mechanical circulatory support.
• Cardiac transplantation can be considered in addition to standard
treatments outlined in Stages A to C.
• Management of volume status can be challenging in these patients
• Restriction of sodium and fluid intake may be beneficial.
• High doses of diuretics, combination therapy with a loop and thiazide
diuretic
• Mechanical methods of fluid removal such as ultrafiltration may
be required. 42

43. • Patients in Stage D may be less tolerant to
 ACE inhibitors (hypotension, renal insufficiency) &
 β-blockers (worsening HF) as high levels of
neurohormonal activation maintain circulatory homeostasis.
43
Initiation of therapy with low doses, then
slow upward dose titration, and close monitoring
for signs and symptoms of intolerance

44. 44
Diuretics
• Reduce morbidity by reducing the symptoms
• Goal is to reduce Body Wt by ~ 1kg/day
•  urinary sodium and water excretion  Reduce preload 
improves pulmonary and systemic venous congestion
• Furosemide 40-80mg Iv initiated to maintain Urine out put
and reduce pulmonary congestion  doubling Q 30-60
minute intil responde seen
• Then switch to PO when congestion resolved for chronic
therapy  dose of PO is double of IV

45. Mineralocorticoid receptor antagonists
Spironolactone & eplerenone
• Beneficent in NYHA Class 3 & 4 patients
• Diuretic effects has little benefit in HF patient
• Spare potassium
• Have benefit in severe LV systolic dysfunction
• Improve long term clinical outcome in patients with sever HF or HF with MI
• Inhibit Oxidative stress caused by aldosterone.
• Protect against bone fractures in HF patientscalcification
• Collagen deposition, thereby attenuating cardiac fibrosis and ventricular
remodeling.
45
spironolactone  start with low doses (12.5
mg/day for
Monitor serum
K+ & renal
function

46. ACEI
• Reduce neurohumoral activation in moderate and severe HF 
preventing peripheral vasoconstriction
• Improve morbidity and mortality
• Up titrated up to Max tolerable dose (without hypotension)
•  serum K+
• Withhold diuretics for 24 hours before starting treatment with a small
dose of a long-acting agent at night  to prevent Hypotension
• Renal function and serum K+ must be monitored  check 1–2 weeks
after starting therapy.
46

47. ARBs
• Indicated for ACEI intolerants
• Reduce Mortality and morbidity reduce
hospitalization
47
Drug Initial Daily Dose(s) Maximum Doses(s)
Candesartan 4-8 mg qd 32 mg qd
Losartan 25-50 mg qd 50 to 100 mg qd
Valsartan 20-40 mg BID 160 mg bid

48. • Carvedilol, metoprolol succinate, bisoprolol.
• β-blockers reduce morbidity & mortality in HFrEF patients.
• Recommended to be used in all stable patients with HF and a
reduced left ventricular EF in the absence of contraindications
• β-Blockers are also recommended for asymptomatic (stage B)
 to  progression of HF
• Reversing ventricular remodeling
• Decreasing myocyte death from catecholamine-induced
necrosis or apoptosis
48
-Blockers..

49. -Blockers..
• Improving left ventricular systolic function,
• Decreasing HR and ventricular wall stress thereby reducing myocardial
oxygen demand, and Inhibiting plasma renin release
• β-Blocker doses should be doubled no more often than every 2 weeks, as
tolerated, until the target or maximally tolerated dose is reached
• In HFpEF, β-blockers helps to lower and maintain low pulmonary venous
pressures by decreasing HR and increasing the duration of diastole.
• β-Blockers should be initiated in stable patients who have no or minimal
evidence of fluid overload
49
Drugs Iniatial Max
Carvedilol 3.125 mg bid 50 mg bid
Bisoprolol 1.25 mg qd 10 mg qd
Carvedilol CR 10 mg qd 80 mg qd
Metoprolol succinate
extended release (metoprolol
CR/XL)
12.5 - 25 mg qd 200 mg qd

50. ACE inhibitors or beta blockers first
• ACE inhibitors provide rapid hemodynamic benefit and
will not exacerbate heart failure in the short run
• The hemodynamic benefits of beta blockers are delayed
(and there may be a transient worsening in cardiac
function when therapy is initiated)
• But long-term improvements in left ventricular ejection
fraction (LVEF) and survival are dose-dependent
50

51. Vasodilators
Nitrates and hydralazine
• Originally combined in the treatment of HFrEF because of their
complementary hemodynamic actions and reduce morbidity & mortality
• Nitrates  decreased preload
• Hydralazine is a direct-acting arterial vasodilator  decrease in SVR
and resultant increases in SV and CO reduce after load
• Benefits extend beyond their hemodynamic actions and are likely related
to attenuating the biochemical processes driving HF progression
• Hydralazine/ISDN be useful in patients unable to tolerate either an ACE
inhibitor or ARB
51

52. Calcium channel blockers
• In patients with atrial fibrillation warranting ventricular rate control
who either are intolerant to or have not responded to a β-blocker,
diltiazem or verapamil should be considered.
• A nondihydropyridine or dihydropyridine CCBs can be
considered for symptom limiting angina & for hypertension.
• Calcium channel blockers such as diltiazem, amlodipine, and
verapamil have little utility in the treatment of HFrEF but useful in
the treatment of HFpEF.
52

53. Digoxin
• Provide rate control in patients with HF and atrial
fibrillation
• In NYHA Class III-IV Reduces the likelihood of
hospitalization for HF , but has no effect on long-term
survival (mortality)
• Has an positive interaction with Erythromycin
• Dose 0.125-0.25 mg/d
53
??

54. Treatment of HFpEF
• Tachycardia is poorly tolerated in patients with HFpEF due to 3 reasons
1. Rapid HRs cause an increase in myocardial oxygen demand and a decrease in
coronary perfusion time promote ischemia even in the absence of
epicardial CAD
2. Incomplete relaxation between cardiac cycles may result an increase in
diastolic pressure
3. Rapid rate reduces diastolic filling time and ventricular filling
• Many clinicians use β-blockers (and nondihydropyridine calcium channel
blockers)
 To prevent excessive tachycardia and produce a relative bradycardia in
patients with diastolic dysfunction
54

55. Therapy of HFpEF…..
• Dugs used in HFrEF are the same as those for treatment of HFpEF but with
few exceptions  may not have the same importance
• The pathophysiologic process that is being altered by the drug, and the
dosing regimen may be entirely different
• For example, β-blockers are recommended for the treatment of both HFrEF
and HFpEF.
 In HFpEF, however, β-blockers are used to decrease HR, increase
diastolic duration, and modify the hemodynamic response to exercise.
 In HFrEF, β-blockers are used in the long term to increase the inotropic
state and modify LV remodeling.
55

56. Approach to Treatment of HFpEF
• Decrease pulmonary venous pressure Diuretics, nitrates, salt
restriction
• Decrease myocardial oxygen consumption β-blockers, diltiazem,
verapamil, ACEI/ ARBs
• Maintain atrial contraction  Cardioversion of atrial fibrillation
• Prevent/treat myocardial ischemia β-blockers, diltiazem, verapamil,
nitrates
• Prevent/regress ventricular hypertrophy Antihypertensive therapy
56

57. Acute Decompensated Heart failure
• If the compensatory mechanisms adequately restore cardiac
output, HF is said to be compensated.
• If the compensatory mechanisms fail to maintain cardiac
output, HF is decompensated and the patient develops
worsening HF signs and symptoms.
• Typical HF signs and symptoms include dyspnea on
exertion, orthopnea, paroxysmal nocturnal dyspnea, fatigue,
and peripheral edema.
57

58. Treatment of ADHF
Diuretics
• IV loop diuretics, i.e. furosemide 40 mg
• Bolus diuretic decreases preload by functional venodilation within 5 to
15 minutes and later (>20 min) via sodium and water excretion,
thereby improving pulmonary congestion.
• Diuretic resistance may be overcome by administering larger IV bolus
doses or continuous IV infusions of loop diuretics.
• Combine with metolazone or hydrochlorothiazide)
• IV inotropes or arterial vasodilators may improve diuresis by
improving central hemodynamics
58

59. Cont..
Positive Inotropic Agents
Dobutamine
• β1- and β2-receptor agonist with some α1-agonist
effects usually vasodilation.
• Potent inotropic effect without producing a
significant change in heart rate
• Initial doses of 2.5 to 5 mcg/kg/min can be increased
progressively to 20 mcg/kg/min on
59

60. Cont..
Positive inotropic Agents
• Milrinone - inhibits PDE III  produces +ve inotropic and
arterial and venous vasodilating effects (an inodilator)
• Usual loading dose of milrinone is 50 mcg/kg over 10
minutes
• Rapid hemodynamic changes are unnecessary, eliminate
the loading dose because of the risk of hypotension.
• Has a higher rate of thrombocytopenia.
60

61. Treatment of ADHF
Vasodilators
• helpful in select patients with refractory volume overload.
• Arterial vasodilators reduce afterload and cause a reflex
increase in cardiac output.
• Venodilators reduce preload
– by increasing venous capacitance  improving symptoms of
pulmonary congestion in patients with high cardiac filling
pressures.
61
Nitroprusside, Nitroglycerin,

62. Vasodilators ….
Sodium nitroprusside
• is a mixed arteriovenous vasodilator
• Hypotension is an important dose-limiting adverse effect of
nitroprusside and other vasodilators.
• Nitroprusside is effective in the short-term management of severe HF
in a variety of settings (eg, acute MI, valvular regurgitation, after
coronary bypass surgery, decompensated chronic HF).
• Nitroprusside has a rapid onset and a duration of action less than 10
minutes, which necessitates use of continuous IV infusions.
62

63. Sodium nitroprusside …
• Initiated therapy with a low dose (0.1–0.2 mcg/kg/min)
to avoid excessive hypotension, and increase by small
increments (0.1–0.2 mcg/kg/min) every 5 to 10 minutes
as needed and tolerated.
• Useual effective doses range from 0.5 to 3 mcg/kg/min
• Taper nitroprusside slowly when stopping therapy
because of possible rebound after abrupt withdrawal
63

64. Vasodilators ….
Nitroglycerin
• IV nitroglycerin decreases preload
• Initiate nitroglycerin at 5 to 10 mcg/min (0.1 mcg/kg/min) and
increase every 5 to 10 minutes as necessary and tolerated.
• Maintenance doses usually range from 35 to 200 mcg/min (0.5–3
mcg/kg/min).
• Hypotension and an excessive decrease in PCWP are important dose-
limiting side effects.
• Some tolerance may develop over 12 to 72 hours of continuous
administration.
64

65. Prevention HF
• Education
• Diet
• Alcohol/Smoking cessation
• Exercise
• Vaccination i.e influenza and pneumococcal
65

66. Evaluation of therapeutic outcome
• Close monitoring of VS at initial stage of diuretic use
• Monitor daily Fluid intake and urine out put
• Daily Body wt. change  wt gain consecutively 1.4-2.3 kg in a week
in out pts should consult to HC provider  so increase the diuretic
dose temporarily
• Symptoms of hypervolemia (i.e light headiness)
• RFT  daily BUN, serum Cr prerenal azotemia of over diuresis
• ACEI intolerant  cough
• Serum K+  spironolactone (Q3day ), ACEI & degoxin use
66

67. Thank you !
67

68. References
• Dipiro pharmacotherapy 10th edi
• Clinical pharmacy and therapeutics 6th edi
• Pharmacotherapy principle and practice
• Applied therapeutics –the clinical use of drugs
• Uptodate 2016
• Medscape
68