Heart Failure

Mohammed Hassn Alnazeer - MClinPharm, BCPS

Cardiac output abnormalities
 Heart Failure (HF)

• HF is a complex clinical syndrome caused by any structural or

functional cardiac disorder that impairs the ability of the ventricle to

fill with or eject blood.

• In mild-moderate states, cardiac output is adequate at rest, but

inadequate when metabolic demand increases.

• HF is frequently due to CAD, with HTN as an important factor.

• HF 5-year mortality is 50%.

 Types of Heart Failure (EF-based)

 Systolic HF (HFrEF) (is the most common type of HF.)

• Reduction in the mechanical pumping force with resultant

decrease in the ejection fraction (EF < 40%).

 Diastolic HF (HFpEF):

• Loss of adequate filling of the ventricle (impaired ability to fill)

caused by abnormal ventricular relaxation. (EF > 50%).

 Both systolic and diastolic often coexist particularly in patients

with CAD.
 Types of Heart Failure (severity-based)

 Acute and chronic HF:

 HF may develop suddenly as in MI, or gradually as in

progressive valvular heart disease.

Anas Mustafa-HF
 Signs & Symptoms of HF

 Symptoms of HF are predominantly those of congestion, caused by

elevated ventricular filling pressure and of organ-system
dysfunction related to inadequate cardiac output.

 Fatigue

 Decreased exercise tolerance.

 Shortness of breath or Dyspnea

 Peripheral and pulmonary edema.

 Cardiomegaly.
 Non-pharmacological Management

1. Treatment of underlying causes (angioplasty, bypass surgery).

2. Control of modifiable risk factors (Bp, DM, LDL, TG,)

3. Restricting intake of salt reduces patient need for diuretic therapy

(2-3 g/day). If Sodium level is low, consider restricting fluids
intake.

4. Regular modest exercise (increase peak exercise capacity).

5. Heart transplantation (limited donors).

 Pharmacological Management

 The following classes of drugs have been shown by clinical

trials to be effective in stable (ambulatory) HF:

ACE inhibitors. ARBs Certain β-blockers.

MRAs Diuretics Cardiac glycosides
Hydralazine-Isosorbide dinitrate Ivabradine

Sacubitril/valsartan

SGLT inhibitors (Dapagliflozin & Empagliflozin)

 Pharmacological Management

• Extensive trials have shown that ACE inhibitors, ARBs, certain β

blockers, MRAs, and combined hydralazine-nitrate therapy are the
only agents in current use that actually prolong life in patients with
Systolic heart failure (HFrEF).

• Diuretics and Digoxin are valuable for symptomatic relief (do not
prolong life).
 HF
HFrEF HFpEF
Systolic HF Diastolic HF
SHF DHF

EF less than EF more than

(40)% (50)%
Pharmacological Management of
HFrEF (systolic)
Who should receive diuretics TTT?

 Patients with signs of sodium and water retention (i.e. peripheral

edema, pulmonary edema, or an elevated jugular venous pressure).

 In a previously untreated patient with preserved renal function

furosemide 40 mg orally will usually produce satisfactory effect.

 If an asymptomatic response is not obtained, the dose of diuretic

should be doubled.
 Who should receive diuretics TTT?

 Patients with resistant edema or symptoms should be considered

for combination oral diuretic therapy or i.v diuretic therapy.

 Patients with severely impaired renal function often need very

high doses of loop diuretics.

 Thiazide diuretics can be used to treat HF, but usually reserved

for less severely affected patients (no pulmonary edema, minimal
elevation of jugular venous pressure) with normal renal function.
Who should receive ACEIs/ARBs TTT?

All HF patients without or with congestive symptoms associated

with reduced systolic ejection fraction (LVSD) or ventricular
remodelling should be treated with ACEIs.

ACEIs/ARBs is recommended in addition to β-blockers for all

patients with an ejection fraction ≤40 to reduce risk of
hospitalisation and premature death (ESC).
 Who should receive β-blockers TTT?

 β-blockers are recommended in addition to ACE inhibitors for all

patients with an ejection fraction ≤40 to reduce risk of
hospitalisation and premature death (ESC).

 Patients already treated with diuretics and/or digoxin and an ACEI

who are clinically stable and in NYHA classes I-III, should be
considered for TTT with β-blocker licensed for use in HF.

 Patients who have been clinically unstable or who are severely

symptomatic (NYHA Class IV), should not receive TTT with βBs.
 Who should receive MRA treatment?

 An MRA is recommended for all patients with persisting

symptoms (NYHA class II–IV) and an EF ≤35%, despite treatment
with an ACE inhibitor and a beta-blocker, to reduce the risk of HF
hospitalisation and the risk of premature death (ESC).

 Recommended to reduce morbidity and mortality in patients after

an MI when they have an LVEF < 40% with symptoms of HF or
an LVEF < 40% and diabetes .
 Who should receive H-ISDN TTT?

 Recommended in addition to ACEIs and β-blockers to reduce

morbidity and mortality for patients with NYHA class III or IV
HFrEF.

 May be useful in patients with current or prior symptoms of

HFrEF who are unable to tolerate an ACE inhibitor or an ARB.

 About H-ISDN and Black population who can or can not take
ACEIs/ARBs???
Role of Sacubitril/valsartan combination

Mechanism of action

(a) Sacubitril – Prodrug metabolized to an active metabolite that

inhibits neprilysin, increasing natriuretic peptides , bradykinin,
and substance P, → natriuretic, vasodilatatory, and anti-
proliferative effects

(b) Valsartan – ARB, selectively blocks the angiotensin 1 receptor

and inhibits angiotensin II–dependent aldosterone release
Who should receive Sacubitril/valsartan?

 In pts with chronic symptomatic NYHA class II or III HFrEF

who can tolerate an ACEI or ARB, replacement by sacubitril
/valsartan is recommended to further reduce morbidity and
mortality (class I recom).

 Sacubitril/valsartan is attractive alternative to ACEIs or ARBS

when BNP is elevated.
Who should receive Ivabradine TTT?

For pts with symptomatic HF pts (NYHA class II and III), stable,
chronic HFrEF (LVEF of 35% or less) who are receiving
evidence-based therapies, including a β-blocker at maximum
tolerated dose, and who are in sinus rhythm (SR) with a HR of ≥
70 at rest (class IIa recommendation).
 Who should receive digoxin treatment?
39

• All patients with HF and atrial fibrillation who need control of the
ventricular rate.

• Patients classified as (NYHA Class III or IV) HF who:

• Remain symptomatic despite diuretic and ACE inhibitor.

• Have had more than one hospital admission for HF.

• Have very poor left ventricular systolic function.

• Patients with HF, treated with a diuretic but unable to use an ACE
inhibitor, or ARB. (H-ISDN is alternative).
 Who should receive SGLT2 inhibitors?
39

• Recommended in addition to ACEI/ARB/ß-blocker therapy in pts

with NYHA class II–IV HFrEF with adequate renal function
regardless of DM. Dapagliflozin (if eGFR ≥ 30 ml/min/1.73m2),
Empagliflozin: (if eGFR ≥ 20 ml/min/1.73m2)

• Benefits: Dapagliflozin and empagliflozin have been shown to

reduce the risk of CV death or worsening HF (Clinical trials).

• Mechanism of action: Promote diuresis, reduce arterial pressure,

and may reduce cardiac hypertrophy and fibrosis.
In any order ??
Pharmacological Management of
HFpEF (Diastolic)
C. Pharmacologic therapy of HFpEF (Diastolic Dysfunction):

Clinical evidence for efficacious agents for HFpEF has generally been
disappointing. Therapies for symptoms, comorbidities, and risk factors
that may worsen CV disease are recommended.

1. Class I recommendations

a. SBP and DBP should be well controlled. HTN impairs myocardial

relaxation and promotes cardiac hypertrophy. (SBP Goal < 130)

b. Diuretics should be used for symptom relief (volume overload).

2. Class IIa recommendations

a. Coronary revascularization is reasonable in patients with CHD who

have angina or demonstrable myocardial ischemia that is judged to

be symptomatic despite optimal therapy.

b. Management of AF is reasonable to improve symptomatic HF.

c. The use of β-blockers, ACE inhibitors, and ARBs in patients with

HTN is reasonable to control blood pressure.

3. Class IIb recommendations: Use of ARBs might be considered to

decrease hospitalizations for patients with HFpEF.

4. Other recommendations

a. Control tachycardia.

i. Tachycardia filling time for ventricles & coronary arteries.

ii. Control of heart rate improves symptoms of HF.

iii. Can use β-blockers or non-dihydropyridine CCBs.

iv. DHP-CCB may cz reflex tachycardia, potentiating diastolic

dysfunction

b. Symptoms of breathlessness can be relieved using nitrates plus diuretics.

Avoid nitrates in HFpEF without concomitant symptomatic CHD.

In the EMPEROR-Preserved trial, the (SGLT2) inhibitor empagliflozin

reduced the composite end point of death or hospitalization for HF in pts
with an EF > 40%. This effect was observed regardless of DM status.
Drugs to avoid or use with caution in HF:

a. NSAIDs, including selective cyclooxygenase-2 inhibitors

i. Promote sodium and water retention

ii. Blunt diuretic response

iii. Increase morbidity and mortality

b. Corticosteroids: Promote sodium and water retention

c. Class I and III antiarrhythmic agents except amiodarone & dofetilide

i. Negative inotropic activity

ii. Proarrhythmic effects

iii. Amiodarone & dofetilide have been proven safe in pts with HF.
 iv. Avoid dronedarone. Contraindicated in patients with symptomatic
HF with recent decompensation necessitating hospitalization or
NYHA class IV HF

d. CCBs (except for amlodipine and felodipine)

i. Negative inotropic activity … (non-dihydropyridine CCBs)

ii. Promotes neurohormonal activation … (other dihydropyridine

CCBs)

iii. Amlodipine and felodipine have been proven safe in patients with
HF and can be added when additional blood pressure reduction is
needed.
e. Minoxidil … (arterial vasodilator)

i. Promotes sodium and water retention

ii. Stimulates the renin-angiotensin-aldosterone system

f. Thiazolidinediones: Promote sodium and water retention

g. Metformin: Increased risk of lactic acidosis (black box warning)

h. Amphetamines (e.g., methylphenidate)

i. α- and β-agonist activity

ii. Cause tachycardia

iii. Proarrhythmic effects

i. Cilostazol: Inhibits phosphodiesterase type 3 … (+ve chronotropic)

j. Itraconazole: Negative inotropic activity

k. Pregabalin

i. Inhibits calcium channels

ii. Lower extremity edema, HF exacerbation

1. A 48-y.o woman with cardiomyopathy. LVEF is 20%; Daily activities
are limited by dyspnea and fatigue (NYHA class III). Medications
include lisinopril 20 OD, furosemide 40 BID, and she is stable on
these doses for the past month. Vital signs B.p 112/70 and HR 72.
Her lung is clear. How to maximize TTT of HF?

A. Add carvedilol.

B. Add ivabradine.

C. Add spironolactone.

D. Add digoxin.
2. J.T. is 62-y-o man with CHD (MI 3 years ago), [HTN], and HF
(LVEF of 25%). Medications include: ASA 81, simvastatin 40 OD,
metoprolol succinate 50 OD, furosemide 80 BID. Vital signs: B.p
128/74 and HR 72. lab results: K 4.1, SCr 2.8, and TSH of 2.6. His
HF is stable & considered NYHA class II. Which is best approach to
maximize TTT of his HF?

A. Discontinue metoprolol and begin carvedilol.

B. Add enalapril.

C. Add spironolactone

D. Add digoxin.
6. Which drug that J.T. (from patient case 5) is currently taking would
be best to discontinue because of his HFrEF?

A. Acetaminophen.

B. Sertraline.

C. Cilostazol.

D. Levothyroxine.
Acute HF
Management of acutely decompensated
HF (ADHF)
 Pharmacological Management

 The following classes of drugs have been shown by clinical

trials to be effective in stable (ambulatory) HF:

 Diuretics → (Loop diuretics +/- Thiazides)

 Venodilators → (Nitroglycerin)

 Arterio/venodilators → (Sodium Nitroprusside)

 Inotropes → (Dobutamine Vs. Milrinone) ??

 Inotrope + vasopressor → (Dopamine )

 Optimize TTT Diuretic +/- venodilator

Dopamine Or Inotrope Diuretic + Inotrope

Arteriodilator
Diuretic + Arteriodilator

In subset 3 & 4, Choice of the drug(s) is based on blood pressure.

 If high Bp → Arteriodilator.
 If normal to low Bp → inotropes. If low Bp & low HR → Dopamine.
Cases for Acute HF
• A 72-year-old man is admitted to the hospital for HF
decompensation. The patient has progressively increased dyspnea
when walking and orthopnea (now four pillows, previously two
pillows), increased bilateral lower-extremity swelling (3+), 13 kg of
weight gain in the past 3 weeks, Which regimen is best for treating
his ADHF?
A. Carvedilol 25 mg twice daily.
B. Sodium nitroprusside 0.1 mcg/kg/min IV.
C. Furosemide 120 mg intravenously twice daily.
D. Milrinone 0.5 mcg/kg/minute.
• A 60-year-old woman with heart failure (HF) (heart failure with
reduced ejection fraction [HFrEF]) is admitted to hospital for
increased shortness of breath and dyspnea at rest. Her extremities
appear well perfused, but she has 3+ pitting edema in her lower
extremities. Her vital signs include Bp 125/70 mm Hg, HR 92
beats/minute. After initiating an I.V diuretic, which intravenous
agent is best to rapidly treat this patient’s pulmonary symptoms?
A. Dobutamine.
B. Milrinone.
C. Nitroglycerin.
D. Metoprolol.
• The previous patient initially responds with 2 L of urinary output
overnight, and his weight decreases by 1 kg the next day. However,
by day 5, his urinary output has diminished again, and his SCr has
risen to 4.3 mg/dL. He was drowsy and confused this morning
during rounds. His extremities are cool and cyanotic, blood pressure
is 89/58 mm Hg, and heart rate is 98 beats/minute. It is believed that
he is no longer responding to his current regimen. Which regimen is
most appropriate for his current symptoms?
A. Milrinone 0.2 mcg/kg/minute.
B. Dobutamine 10 mcg/kg/minute.
C. Sodium nitroprusside 0.1 mcg/kg/minute.
D. Phenylephrine 20 mcg/minute.
Thank You