this is a powerpoint describing the latest advances in management of heart failure.

1. DR.C.K. MULWA
Management of heart failure

2. Objectives
 Understand basics of heart failure pathophysiology.
 Understand the pillars of heart failure mx based on guideline directed medical
therapy(GDMT) for the treatment of heart failure.

3. Heart Failure: definition
 A progressive disorder in which the heart is unable to pump sufficient blood to meet the needs
of the body (decreased cardiac output).
 Ejection fraction, A measure of how much blood is pumped out of the ventricles with each
contraction.
 Normal: 55-70%
 Heart failure with reduced ejection fraction-
clinical syndrome typically with signs and symptoms and an EF < 40%
 Heart failure with preserved ejection fraction-
Clinical syndrome with signs and symptoms of heart failure and EF of >40%

4. Pathophysiology: Causes of heart failure
Left ventricular systolic dysfunction
 Coronary artery disease
 Idiopathic dilated cardiomyopathy (DCM)
 Vulvular heart disease
 Hypertension
 Toxin induced cardiomyopathies (e.g., doxorubicin, herceptin, alcohol)
 Congenital heart disease

5. Pathophysiology
↑ neurohormonal
activation
(SNS and RAAS)
↑ fluid retention
↑ vasoconstriction
Diuretics
Digoxin
Vasodilators
RAAS inhibitors
BB
SGLT2i
Imbalance
between
physiologic
demands and
cardiac output
BB, β-blockers; RAAS, renin-angiotensin-aldosterone system; SGLT2i, sodium glucose co-transporter 2 inhibitors; SNS, sympathetic nervous
system.
Parker RB, et al. Chronic heart failure. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed.
McGraw Hill; 2017.

6. Pathophysiology: Counter-regulatory
changes in HF
In LV systolic dysfunction, the body activates several neurohormonal pathways to increase
circulating blood volume.
The sympathetic nervous system
 Increases heart rate and contractility,
 Causes arteriolar vasoconstriction in nonessential vascular beds,
 Stimulates secretion of renin from the juxtaglomerular apparatus of the kidney.
 Unfortunately, catecholamines aggravate ischemia, potentiate arrhythmias and promote
cardiac remodelling

7. Pathophysiology: Counter-regulatory
changes in HF
Stimulation of the renin-angiotensin system:
 Results from increased sympathetic stimulation and decreased renal perfusion
 Results in further arteriolar vasoconstriction and release of aldosterone.
 An increased aldosterone level, in turn, leads to sodium and water retention

8. Pathophysiology: Counter-regulatory
changes in HF
Baroreceptor stimuli
 Lead to vasopressin (antidiuretic hormone, ADH,) release from the
hypothalamus, causing reabsorption of water in the renal collecting duct.
NB: Although these neurohormonal pathways initially are compensatory and
beneficial, eventually they are deleterious.

9. Pathophysiology :Myocardial changes in
heart failure
 In a normal heart, a compensatory increase in performance occurs as the stretched
myocardium responds through increased elastic recoil.
 In the failing heart, this property of cardiac muscle recoiling under stretch is
diminished and therefore the heart dilates abnormally to accommodate the
increased ventricular load.
 Failure of the heart to handle the increasing ventricular load leads to pulmonary and
venous congestion.
 At the same time, the increased tension on the ventricular wall in heart failure
raises the myocardial oxygen requirements thus predisposing the patient to
myocardial ischaemia .

10. Pathophysiology: Myocardial changes in
heart failure
 The failing heart may show cardiac enlargement due to dilation but this is
reversible with treatment.
 An irreversible increase in cardiac muscle mass (cardiac hypertrophy) may
occur with progression of heart failure and is usually a consequence of long
standing hypertension.
 While hypertrophy may initially alleviate heart failure, the increased muscle mass
results in increased workload and oxygen consumption.

11. Pathophysiology: Counter-regulatory
changes in HF
Other effects: natriuretic peptides
 Natriuretic peptides are hormones released by secretory granules in
cardiac myocytes in response to myocardial stretching.
 They have a beneficial influence in heart failure, including systemic and
pulmonary vasodilation, possible enhancement of sodium and water
excretion, and suppression of other neurohormones.

12. The Vicious Cycle of Congestive Heart Failure
Decreased Blood Pressure and
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
LV Dysfunction causes
Decreased cardiac output

13. Homeostatic Responses to Impaired Cardiac Performance
Response Short-Term Effects* Long Term Effects
Salt and water
retention
Augments preload to increase
cardiac output
Pulmonary congestion and
peripheral edema
Vasoconstriction Maintains blood pressure for
perfusion of vital organs
Exacerbates pump
dysfunction (increased
cardiac afterload and
energy expenditure)
Sympathetic
stimulation
Increases heart rate and ejection
(increased output)
Increases energy
expenditure and causes
arrhythmias
Cardiac
hypertrophy
Adaptive: increased sarcomere
number with increased cardiac
output
Maladaptive: accelerated
cell death, arrhythmias

14. Symptoms of Heart Failure
F Fatigu
e
A Activities
limited
C Chest congestion
E Edema or ankle
swelling S Shortness
of breath

15. NYHA Classification of Heart Failure
NYHA
Class
Description
I No symptoms with ordinary physical activity such as walking or
climbing stairs
II Slight limitation with dyspnoea on moderate to severe exertion such as
climbing stairs or walking uphill
III Marked limitation of activity and less than ordinary activity causes
dyspnoea e.g. restricting walking distance and limiting climbing to
one flight of stairs
IV Severe disability, dyspnoea at rest and the patient is unable to carry on
physical activity without discomfort

16. Treatment of Heart Failure
 Correction of systemic factors
 Thyroid dysfunction
 Infections
 Uncontrolled diabetes
 Hypertension
 Lifestyle modifications
 Dietary sodium restriction to 2g/day and fluid intake restriction to 2L/day
 To lessen congestion and decrease the need for diuretics
 Alcohol cessation
 Smoking cessation
 Others: daily weight monitoring, light aerobic exercise.
 Pharmacological management

17. Pharmacological management of HF
 Cardiac performance is determined by:
 Preload,
 Afterload,
 Myocardial contractility
 Heart rate.
 Treatment targets these aspects, often by blocking the counter-regulatory
mechanisms.

18. Pharmacological management of HF
Cardiac
target
Description Effects of drugs
Cardiac preload Cardiac preload is increased by salt and water
retention,
capacitance vessel tone and sympathetic nervous
system activation.
Drugs can reduce blood volume
(diuretics)
and reduce capacitance vessel tone
(vasodilators).
Afterload Afterload is determined by the systemic vascular
resistance
and by aortic stiffness.
Drugs that relax arterial smooth
muscle
reduce cardiac afterload.
Myocardial
contractility
Positive inotropes (i.e. drugs that increase the force of contraction of the heart) can improve
cardiac performance temporarily by increasing contractility, but at the expense of increased
oxygen consumption and risk of dysrhythmia.
Heart rate Cardiac function deteriorates as heart rate increases
beyond
an optimum, due to insufficient time for filling during
diastole.
Heart rate can be slowed by
negative chronotropes(i.e. drugs
that slow the heart).

19. Pharmacological Mx:
 ACE inhibitor e.g. Enalapril
 ARB e.g. Losartan, Valsartan
 Aldosterone antagonists, e.g. Eplenonone, Spirilonolactone
 Angiotensin ii receptor-neprilysin inhibitors ( ARNI)- Sacubitril/Valsartan
 Beta blockers- Bisoprolol, Carvedilol
 Cardiac glycosides- Digoxin
 Direct vasodilators- Hydralazine

20. Pharmacological Mx:
 Loop diuretics e.g. Furosemide, Torsemide
 Thiazide diuretics e.g HCTZ
 Nitrates- e.g. Isosorbide mononitrate
 Vasopresssin antagonists e.g. Tolvaptan
 ‘I’ channel blockers- e.g. Ivabradine
 Sympathomimetics e.g. Noradrenaline, dobutamine
 Phosphodiesterase inhihibitors e.g. Milrinone
 SGLT2i- e.g. Empagliflozin
 CCBs- e.g. Amlodipine

21. Guideline directed medical therapy(GDMT)
for the treatment of heart failure.
 Newest guidelines on mx of HFrEF indicate thar patients should be started on
quadriple therapy with the 4 pillar drugs at once at low doses then doses titrated
up
 There are 4 pillars of GDMT tx of HFrEF.
1. Beta Blockers
2. Mineralocorticoid receptor antagonists
3. Angiotensin 11 receptor neprilysin inhibitors/ ACEis
4. Sodium Glucose cotransporter 2 inhibitors

22. Titrate to target dose based on
patient tolerance and add additional
therapy as needed.
ARNI
or
ACEi/AR
B
Consider
additional
pharmacological
therapies
Diagnosis of HF with
EF
<40%
GDMT
African
American
NYHA III-IV

Hydral/nitrate
s
Beta SGLT2i
MRA
Blocker
Diuretic
s
(PRN)
NYHA I-III EF
≤35% >1
year
expected
survival 
ICD
NYHA II-III (IV
if
ambulatory),
with NSR and
QRS
<150msec
 CRT-D
2022 American Heart Association/American
College of Cardiology HF
Guidelines
Heidenreich PA, et al. Circulation. 2022;145(18):e895-
e1032.

23. Beta blocker therapy
 Moa; Act by combating the sympathetic overactivity which occurs in
response to the failing heart
 They also minimize the abnormal structural and physiological changes
that occur in the cardiac muscle in response to the overactivity.
 Contraindications/cautions
 Heart rate <60 bpm (bradycardia)
 COPD, asthma
 Heart conduction abnormalities: 2nd or 3rd degree block
 Diabetes

24. Beta-Blocker Clinical
Pearls
Possibly
most
beneficial
class
Assess
fluid
status
Avoid non selective BB in asthma
• Reduces all-cause mortality by >30%
• Benefit within 30 days
•Do not start when patient is
“wet”
•Decreases cardiac output (negative
inotrope/chronotrope)
optimize loop diuretics PRN
Avoid abrupt discontinuation
Target
dose /
HR
• Start low and titrate
slow
HR, heart rate.
Greene SJ, et al. J Card Fail. 2022;28(3):370-384; Heidenreich PA, et al. Circulation. 2022;145(18):e895-e1032; Fox K, et al. Lancet.
2008;372(9641):817-821.

25. Dosing and
Details
Carvedil
ol
≤85 kg: 25 mg
twice
a day
>85 kg: 50
mg twice a
day
With food
Metoprolol
succinate
200 mg
daily
Becomes less
selective at
higher doses
Bisoprol
ol
10 mg
daily
Heidenreich PA, et al. Circulation. 2022;145(18):e895-
e1032.
Targe
t
dose
s

26. ACE inhibitors
 MOA: Decrease the afterload on the heart by reducing formation
of angiotensin II which is a potent vasoconstrictor on the arterial
system.
 They also reduce venous congestion and preload by inhibiting the
release of aldosterone from the adrenal cortex.
 Begin therapy low and titrate up as possible:
 Enalapril – 2.5 mg po BID
 Captopril – 6.25 mg po TID
 Lisinopril – 5 mg po QDaily
 If the patient cannot tolerate, switch to ARB

27. Angiotensin Receptor Neprilysin Inhibitor(
ARNI)
Valsartan/ Sacubitril
MOA: combines the action of Valsartan ( ARB) and sacubitril
Valsartan
Angiotensin ii receptor blocker that decreases BP by blocking vasoconstriction and
aldosterone- secreting effects of angiotensin ii reducing salt & water retention
Sacubitril
Prevents degradation of endogenous natriuretic and vasodilator peptides which
results to vasodilation and diuresis
When combined the 2 reduce the strain of the failing heart

28. • NYHA class 2-3 HFrEF
• Contraindicated in history of angioedema/ Cough on ACEi
• ARNI should not be administered within 36 hours of the last dose of an ACEi due to
risk of angioedema
• ARNIs lower BP more than ACEi or ARB
• Patients on ACEi or ARB should be transitioned to ARNI
• Start sacubitril/valsartan 49 mg/51 mg twice a day, double in 2-4 weeks
• Target 97/103 mg
• Target doses reduce Mortality and hospitilization as demonstrated in the paradigm- HF
study
.
Sacubitril/Valsartan Clinical
Pearls

29. Angioedema
Risk
Heidenreich PA, et al. Circulation. 2022;145(18):e895-
e1032.
Inactive
metabolite
s
Inactive
metabolite
s
Bradykini
n
X
A
CE
Ne
X
prilys
in
Sacubitril
ACEi
Need 36-hour washout period from ACEi to prevent
angioedema

30. Potassium-sparing diuretics
Spironolactone, eplerenone
 Antagonize the effects of aldosterone at the late distal tubule and cortical
collecting tubule.
 They induce diuresis
 improve survival in HF
 Dosing for both spironolactone and eplerenone: start at 25 mg daily
and may increase to 50 mg after a month
 Eplerenone, less endocrine abnormlities such as gynacomastacia, bph

31. Contraindications and precautions
 These agents can cause severe, even fatal hyperkalemia in susceptible patients.
 Oral K+ administration should be discontinued if aldosterone antagonists are administered.
 Patients with chronic renal insufficiency are especially vulnerable and should rarely be treated with aldosterone
antagonists.
 Concomitant use of other agents that blunt the renin-angiotensin system ( β-blockers or ACE inhibitors)
increases the likelihood of hyperkalemia.
 Patients with liver disease may have impaired metabolism of triamterene and spironolactone, and dosing must
be carefully adjusted.
 Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole) can markedly increase blood levels of eplerenone.

32. Sodium Glucose Co-Transporter 2 Inhibitor
Empagliflozin or Dapagliflozin
• NYHA class 2-4
• 10 mg initial and target dose
• DAPA-HF and EMPEROR-Reduced trials: cardiovascular (CV)
death ↓
≈25% and HF hospitalization by ≈30%
• Best evidence in mildly reduced, improved, and preserved HF
Docherty KF, et al. JACC Heart Fail. 2020;8(10):800-810; Heidenreich PA, et al. Circulation. 2022;145(18):e895-e1032; Inspra. Prescribing
information. Pfizer; 2008.

33. Inappropriate Medications in HF
Non-dihydropyridine calcium channel blocker (verapamil, diltiazem; negative inotrope)
Stimulants (decongestants, amphetamines; Increase oxygen demand)
Nonsteroidal anti-inflammatory drugs, corticosteroids (fluid retention, increase vascular resistance)
α1 blocker (RAAS stimulation, increase HR)
DPP4 (Dipeptidyl peptidase-4) (mechanism unknown, can increase risk of angioedema with
ACEi/ARNI) Ci
Thiazolidinedione (fluid retention)
El Hadidi S, et al. Eur Heart J Cardiovasc Pharmacother. 2022;8(2):187-210; Heidenreich PA, et al. Circulation.
2022;145(18):e895-e1032.

34. Take home points
• HF is often suboptimally managed and continues to be associated with high
hospitalization rates and mortality
• GDMT for HFrEF is based on the “4 pillars”: ARNI, BBs, MRA, and SGLT2i
• Medications should be initiated and up-titrated with the aim of achieving target
doses in a reasonably short time period
• Look out for drugs that worsen HF

35.  THANK YOU