Therapy 1: Heart failure

Done By: Luma Al-Amad

Contents:
✓ Pathophysiology of HF

✓ Stages of HF

✓ Heart failure with Preserved, Mildly reduced, improved EF

✓ Drugs of Unproven Value or That May Worsen HF

✓ Main therapy (GDMT)

✓ Special populations

✓ Add-on therapy

✓ Other drug therapy

✓ Stage D

✓ Acute Decompensated Heart Failure (ADHF)

✓ Cases/questions (last 2 pages)

HF Page 1
Pathophysiology of HF

Problems in HF:
- Ventricle filling: enlargement of heart (hypertrophy) so ventricles are thicker, so its capacity decrease

- ventricle emptying/pumping/ejectionEF
In ejection, 30% of blood remain in heart, because contraction isn't enough. The remained blood could cause edema and cardial
infusion.

➢ Overall problem: CO(decreased)

Physiological mechanisms
that are activated because Activate RAAS system to return water
of this problem from kidney
Which will be our But these mechanisms worsening HF
target(drug target)

Carotid sinus firing:

Increase load on Heart
Because of increase in force of contraction
so O2
Demand increase Lead to MI or ischemia
or other
Cardiac conditions

Increase in ADH cause Edema

Thickening of atrophy
muscle which
lower the space
of ventricle

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Stages of HF

► Stage A: no symptoms or signs, only at risk of HF

Such as: HTN, CVD, Obesity, cardiotoxic agents, family history of cardiomyopathy, and genetic variant

- We recommend them to start with non-pharmacology, but only one group have drug recommendation: diabetic
patient
- How diabetes lead to HF? When serum sugar levels are high, causing activation of stress pathway: increase
cortisol: increase contractility and load on heart. Also sympathetic and vasoconstriction. It is: sodium-glucose-
cotransporter-2 (SGLT2)
However, it's Not used in real life

► Stage B: Pre-HF
Recommendations:
1- LVEF less than 40%: ACEI and BB
2- History MI OR ACS: statins
3- history of MI or ACS and LVEF less than 40%: BB+ACEI+statin
4- 40 days post-MI with LVEF less than 30% + NYHA class 1(no symptoms) + GDMT + expectation of survival for less more
than 1y: ICD
5- Diabetic patients with LVEF less than 50%: thiazolidinediones should not be used
6-LVEF less than 50%: nondihydro CCBs should not be used (negative inotropic effect)

Class1 is combination between A+B, without limitations

If patient have HF and take treatment (not stage A) but the symptoms
and signs are disappeared of HF, that doesn't mean he will be back to
stage B. he is stage C

Class2: slight limitations

Class3: marked limitations, comfortable at risk

Class4: discomfort at any activity

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Preserved, Mildly reduced, improved

Reduced Mildly Reduced Ejection Improved Ejection Preserved

Fraction Fraction Ejection Fraction
Same treatments, lower GDMT should be Beta blocker isn't
recommendations continued recommended
Diuretics(in case of edema), Rest of therapy is
SGLT2i, ACEI, ARB, ARNI, the same
MRA, BB SGLT2i, MRA, ARNi,
ARBs

LVEF ≤ LVEF 41%–49% Previous LVEF ≤40% and a LVEF ≥50%

40% follow-up measurement of
LVEF >40%

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Drugs of Unproven Value or That May
Worsen HF
-Until now (in HTN+HF), we don’t recommend nondihydropyridine CCBs (Diltiazem/Verapamil)
So,

Not recommended:
Exacerbate HF:

Nondihydropyridine (Verapamil + Diltiazem)

NSAIDs (worsen symptoms)

class IC antiarrhythmic medications and dronedarone (may increase the risk of mortality)

thiazolidinediones increase the risk of worsening HF symptoms and hospitalizations.

dipeptidyl peptidase-4 (DPP-4) inhibitors saxagliptin and alogliptin :In patients with type 2 diabetes and high cardiovascular risk

NO benefit drug therapy:

1- Anticoagulant
Not recommended in n patients with chronic HFrEF without a specific indication

2- Dihydropyridine

3- vitamins, nutritional supplements, and hormonal therapy

S16

Factors Precipitating/Exacerbating HF

- Cardiac events are a frequent cause of worsening HF (CAD, Afib, HTN)

– Noncardiac events (Pulmonary infections , PE, DM, CKD, hypothyroidism, and hyperthyroidism)

– Nonadherence with prescribed HF medications or with dietary recommendations (eg, sodium intake and fluid
restriction)

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 medications may be started simultaneously at
Main therapy (GDMT) initial (low) doses recommended for HFrEF.
Or may be started sequentially, with sequence guided by clinical or other
factors, without need to achieve target dosing before
initiating next medication. Medication doses should be
increased to target as tolerated.
Remember 4 main drugs:

1- Drugs work on RAAS system: ARNI or ACEI or ARBs

2- BB
3-MRAs
4-SGLT2i (empagliflozin, dapagliflozin)
5- Diuretic as needed

- All of them are given for stage C, even if symptoms and signs are treated, because they decrease mortality, morbidity
(complications of HF)

-Loop Diuretics preferred for any type of edema/ foot overload in HF (congestive HF)
- in case of nonresponsive loop (refractory edema), we will increase the dose, or IV loop, or add thiazide
- MRAs decrease overload
- Remember: in HTN we start always with thiazide (it have better action in case of HTN)
- In case of HTN+HF patient, we choose: Thiazide

• We start with ARNI, if isn't feasible: ACEI

- Example: patient take ACEI and have angioedema or cough, can we switch it with ARNI? NO
ARB is recommended
- ARNI & ACEI should not be administrated to patients with history of Angioedema
- In case of tolerated ACEI, I can switch with ARNI because level of evidence of reducing mortality and
morbidity for ARNI is higher than ACEI

• HFrEF : BB (Bisoprolol/Carvedilol/Metoprolol (MBC)

- (reduce mortality)
1. MBC not always cardio selective, such as Carvedilol
2. So Carvedilol should not be administrated to patients with Asthma
3. Metoprolol is cardio-selective

• MRAs (mineralocorticoid receptor antagonist)

1. Spironolactone and eplerenone are recommended in NYHA (From 2-4)
- Why not for class1? Because it may be in B not C
- Recommended when eGFR higher than 30 + serum K lower than 5, (( if 5 and higher risk of life-threatening hyperkalemia))
- Monitoring: K, renal function, diuretic dosing to minimize risk of hyperkalemia and renal insufficiency
Discontinued when: potassium can't be maintained at lower than 5.5

• sodium-glucose-cotransporter-2 (SGLT2) Inhibitor

- high evidence in reduction of mortality and morbidity
addition of this class of therapy to the regimens of patients with HFrEF provides improvements in clinical outcomes and in
patient-reported outcome measures.
- Should be used in stage A type 2 diabetes to prevent hospitalization

Important points:

- even in zero symptoms and EF is improved, must continue these drugs because my target to decrease mortality and morbidity

-Initiation of an ARNI/ACEI/ARB is often better tolerated when the patient is still congested (“wet”) (means edema), whereas
beta-blockers are better tolerated when the patient is less congested (“dry”) with an adequate resting heart rate; beta blockers
should not be initiated in patients with decompensated signs or symptoms.

- so if patient have edema and I don’t want to give him BB (because might have bad response) → initiates ARBs or ACEI and Loop
diuretics, after period of time I will start to give him Beta blocker
edema

- After a diagnosis of HF is made, adjustment of therapies should occur every 2 weeks, and some patients may tolerate more rapid
titration of GDMT.

- Reassessment of: BP, kidney function, electrolytes, ventricular function

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Special populations

African American (combination of hydralazine and isosorbide dinitrate)

- In NYHA class 3 or 4 (limited ph. Activity or at rest have symptoms)
Receiving optimal medical therapy, the combination of hydralazine and isosorbide
dinitrate is recommended to improve symptoms and reduce morbidity and mortality.
- we don’t stop ACEI !

- remember: hydralazine(vasodilator) was in HTN crises + HTN pregnancy

- remember: isosorbide dinitrate given in angina, they are vasodilator so we give it here

- because they already have problems in their vessels so they have lower responses than
other population, that’s why I need to add (MRA) to enhance the outcome.

-If patients can't be given 1st line (specifically ACEI/ARBs/ARNi), combination of

hydralazine and isosorbide dinitrate might be considered

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Add on therapy
(additional medical therapies that may be considered for patients with HF)

Before starting with add-on therapy, I must make sure that patient adheres to his drugs

1- Ivabradine → decrease sinus load of heart, which decrease electrical conduction →

improve HF
When to use? Chronic HFrEF less than 35%, class 2-3, receiving GDMT, including
a beta blocker at maximum tolerated dose, HR have to be higher than 70 at rest.

2- Vericiguat (new)
- Added when recurrent hospitalization
HF
- Added when EF less than 45
- Added worsening of symptoms and signs of HF (already on GDMT)

3-Digoxin
- recommended in patients with symptomatic HF even with taking GDMT
- there is no worsening, no recurrent hospitalization, but symptoms aren't improved

All of them can reduce hospitalization

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Other drug treatment

Omega-3 polyunsaturated fatty acid (PUFA) supplementation

- when class 2-4, reduce mortality and cardiovascular hospitalizations. Improve outcomes
- the use is reasonable

potassium binders

(patiromer, sodium zirconium cyclosilicate)

- when patient experience Hyperkalemia (but not with MRAs), only with ACEI, ARNI, ARBs
Because: I can discontinue MRA in case of hyperkalemia, but in case of hyperkalemia with
ACEI, ARNI, ARBs I cant

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Stage D

- Presence of symptoms even at rest

-cannot be discharged from the hospital without special intervention

Specialized therapies in addition to standard treatments outlined in Stages A to C.

A – mechanical circulatory support (MCS)

B – continuous IV positive inotropic support

• positive inotropic (increase force of contraction)
• Such as: Dopamine, Dobutamine
• Chronotropic (increase rate of contraction)
• In stage D recommendation for inotropic because it improve ejection of blood and
reduce side effects that are resulted from decreased oxygenation

C – cardiac transplant

D – hospice care

HF Page 12
 Acute Decompensated HF (ADHF)

Exacerbation of HF

patients with:
new or worsening signs or symptoms of HF (often as a result of volume overload and/or low cardiac output [CO]) requiring medical
intervention such as an emergency department visit or hospitalization

May include:
HFrEF
HFpEF

Cardiac index:
Indicate: CO in the body
✓ If its ↑ that means: vasodilation Warm
✓ If its ↓ that means: low CO, Cold (blood isn't reaching all body and extremes)

Pulmonary capillary wedge pressure (PCWP)

✓ If its ↓ that means: Dry
✓ Increasing in PCWP → edema (wet)
SO,

(1) Dry & Warm (3) Wet & Warm

(2) Dry & Cold (4) Wet & cold

1 Dry & Warm No edema life-threatening, have ↑symptoms Optimized Chronic oral medications S124
No need for new intervention

2 Dry & Cold No edema, but low CO can lead to necrosis
Cool extremities, ↓urine output, ↑serum
urea
Assessment of volume status (PCWP) if less than
15: give IV fluids
PCWP (15-18) but cold, no need for fluids, need
assessment of systolic BP. If higher or equal 90:
give IV vasodilator or positive inotropes

If systolic less than 90, give positive inotropic

without vasodilator (avoiding hypotension)

+- Vasopressin can be given

Last option: mechanical circulatory support

3 Wet & Warm Loop diuretics

- + IV Vasodilator (why? Because of constriction,

to increase blood flow of kidney so fluids can be
released faster)

In case of persistent symptoms: thiazide with

loop, if need further management: PAC

What if symptomatic relief? Back to (1)

(optimize oral therapy)

4 Wet & cold v.high vasoconstriction Assess SBP: if 90 or higher: IV diuretic +

(worst) Fluids around lungs and heart vasodilator

If SBP less than 90: IV inotrope + diuretic but no

vasodilator (because risk of hypotension)
+ - vasopressor and +- PAC

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Cases
Wednesday, December 6, 2023 12:02 AM

57-year-old African American male with a 4-year history of HFrEF continues to have fatigue and dyspnea on exertion. His serum electrolytes, creatinine clearance, and
other lobs ore within normal limits. His LVEF by echo is 30%. His blood pressure is 130/85 mm Hg and heart rate is 60 bpm. His cardiovascular drug regimen is
unchanged over the previous 3 months and includes: Enalapril 10 mg twice daily, Carvedilol 25 mg twice daily, Furosemide 40 mg twice daily, hydralazine/isosorbide
dinitrate, Spironolactone 25 mg daily. Which is the most appropriate change to his therapy?

a. Add amlodipine

b. Add digoxin

c. Change enalapril to sacubitril/valsartan

d. Add ivabradine (can't use it because HR under recommended)

e. Change enalapril to candesartan

Enalapril: ACEI
Carvedilol: BB
Furosemide: Loop diuretic
Spironolactone: MRA
sacubitril/valsartan: ARNI

Not cardio-selective)

Lisinopril: ACEi
Carvedilol: BB
Spironolactone: MRA
Furosemide: Loop diuretic
Candesartan: BB (he already take Carvedilol)
Eplerenone: potassium-sparing diuretic (he already take spironolactone)
Amlodipine: dihydro CCB (not part of the therapy)

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Cases

Cold and hypotensive: can't give vasodilator

Inotropic: dopamine
Enalaprilat: ACEI
Na nitroprusside: Vasodilator

Metolazone: thiazide
Furosemide: Loop

Ibuprofen: NSAID
Amlodipine: CCB Dihydro
Atorvastatin

Digoxin have no benefit on HF (on mortality and morbidity)

Its only given in unimproved symptoms

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