HF

Question 1

What COMPENSATORY RESPONSES BECOME MALADAPTIVE LONG TERM

Answer 1

• Myocyte dysfunction • Ventricular remodeling • Hypertrophy, fibrosis • Myocyte death

Question 2

HF treatment
Preload, afterload, contractility> SV>CO

Answer 2

^ preload + ^ afterload = decreased SV } decreased
Decreased contractility= decreased SV }. CO

Therefore we want to reduce preload+ afterload
AND INCREASE Contractility

Question 3

HF + tx aims to

Answer 3

Causes breathlessness and distress
Treatment aims to:
 Prolong life
 Relieve symptoms
 Improve quality of life

Question 4

ACEIs/ARBs
(Afterload, preload)

Answer 4

 Reduce cardiac afterload
 Reduce cardiac preload
 Delay progression of the disease
 Prolong life
 ACEIs may be used
as first-line treatment
 ARBs are a reasonable alternative
in case of ACEI intolerance

Question 5

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
Examples

Answer 5

Some patients may be candidates for initial
therapy with an ARNI
—> (sacubitril-valsartan)

Question 6

ARNI MoA

Answer 6

•Neprilysin degrades natriuretic peptides and ATII •Natriuretic peptides (B-type natriuretic peptide-
BNP): hormones released in HF to counteract the
effects of compensation:
-Natriuresis (counteracts NA retention)
-Vasodilation (counteracts Vasoconstriction)
-Inhibition of renin, ATII, aldosterone, ADH release
and action RAAS pathway

Question 7

Eligibility criteria for initial therapy with an ARNI

Answer 7

 Current or prior elevated B-type natriuretic
peptide (BNP) level or N-terminal proBNP
 Hemodynamic stability (BP ≥100 mmHg)
 No history of angioedema
 Access to medication

Question 8

Adverse effects of ARNI

Answer 8

-Hypotension
-hyperkalemia (RAAS pathway)
-cough
-dizziness (from hypotension)

Question 9

β-BLOCKERS IN HF

Answer 9

 Considered first line treatment in combination with ACEIs, ARBs or ARNI
 But NOT in acute, decompensated HF

Question 10

β-BLOCKERS IN HF
Examples

Answer 10

Metoprolol, carvedilol, bisoprolol

Question 11

EFFECTS OF β-BLOCKERS IN HF

Answer 11

 SA node: Decrease heart rate
 Myocardium: Decrease contractility
 Renal: Decrease renin release, decrease RAAS
activation, reverse vasoconstriction, prevent fluid
retention —> Decrease blood pressure
 Save energy and oxygen demand
 Reduce Ca cycling and propensity for arrhythmias  Halt progression of the disease
 Improved survival

Question 12

DIURETICS
Chronic tx and combination + monitor

Answer 12

 Chronic treatment with ACEIs leads to ‘aldosterone escape’’
—Circulating aldosterone concentrations return towards pre-treatment values
 Combining ACEIs/β-blockers with aldosterone antagonists (spironolactone, eplerenone) further reduces mortality in more advanced HF
 Monitor K+ levels with ACEIs/ARBs/ARNI in combination with aldosterone antagonist
 Other diuretics e.g. loop/thiazide diuretics used to treat congestion but do not prolong life

Question 13

ALDOSTERONE ANTAGONISTS MoA

Answer 13

Aldosterone
 ↑Na+ & H2O retention —->↑ Preload & BP
 Myocardial fibrosis
 Endothelial dysfunction
 Promotes arrhythmias

Aldosterone antagonists in HF
Decrease preload
Improve prognosis

Question 14

OTHER DRUGS FOR SECONDARY TREATMENT OF HF

1.Hydralazine plus nitrate (isosorbide nitrate)

Answer 14

• Hydralazine reduces afterload, while nitrates
reduce preload
• Addition to HF regimen, especially in black patients, improves survival

Reduces TPR

Question 15

OTHER DRUGS FOR SECONDARY TREATMENT OF HF

2. Digoxin
3. Ivabradine

Answer 15

2.
• Does not reverse/retard progression of HF
• Reduces hospitalization (in combination with
other HF drugs)

Question 16

OTHER DRUGS FOR SECONDARY TREATMENT OF HF
4. Sodium-Glucose Co-Transporter Inhibitor 2

Answer 16

• Recent guidelines recommend use of a
SGLT2i to reduce hospitalization for HF and
CV mortality, irrespective of presence of T2D

Question 17

DIGOXIN

Answer 17

 Inhibition of Na+/K+ ATPase

 Increases intracellular Ca2+

 Positive inotropic agent

Question 18

DIGOXIN Effects on the heart

Answer 18

 Cardiac slowing and reduced rate of conduction
through the AV node
-Due to increased vagal activity
 Increased force of contraction
 Disturbances of rhythm
-Block of AV conduction, increased ectopic
pacemaker activity

Question 19

Digoxin indications

Answer 19

 Treatment of HF in patients who remain
symptomatic despite optimal use of ACEIs
and diuretics
 Atrial fibrillation: due to AV conduction
slowing

Question 20

Digoxin Adverse effects

Answer 20

Common and severe
 Narrow therapeutic index
-Care in elderly and renal impairment
-Monitoring may be useful
 Disturbs sinus rhythm
-Can progress to AV block
 Anorexia, nausea
 Ectopic beats
 Visual effects (yellow, blurry vision)

Question 21

Digoxin
The effect of extracellular potassium

Answer 21

 Effect of digoxin increased if less K+, thus more
toxicity i.e. arrhythmias
 If more K+, then less effective
 Important: Diuretics-digoxin interaction
 Treatment of digoxin toxicity: normalize K+ levels,
anti-digoxin Fab fragments, anti-arrhythmics,
pacing

Question 22

Acute HF TX

Answer 22

 Loop diuretic-drugs of choice

 IV glyceryl trinitrate (GTN): Predominantly mediates venorelaxation
-Central venous pressure reduction (reduced preload)
 Mild effects on arteries
-Reduced afterload
 Can be combined with diuretics, if symptoms persist, especially with elevated BP

Question 23

ACUTE HF WITH SYSTOLIC DYSFUNCTION: INOTROPES

Answer 23

1. Dobutamine
2. Dopamine
3. PDE3 inhibitors : amrinone, milrinone

Question 24

ACUTE HF WITH SYSTOLIC DYSFUNCTION: INOTROPES
1. Dobutamine

Answer 24

 Selective β1-adrenergic receptor agonist
 Drug of choice in !systolic dysfunction !

Question 25

ACUTE HF WITH SYSTOLIC DYSFUNCTION: INOTROPES 2.Dopamine

Answer 25

 Positive inotrope  May increase renal blood flow

Question 26

ACUTE HF WITH SYSTOLIC DYSFUNCTION: INOTROPES 3. PDE3 inhibitors: amrinone, milrinone

Answer 26

 Increase cAMP in heart muscle & smooth muscle: positive inotropy, decreased TPR  Improve hemodynamic indices  Worsen survival: arrhythmias