Chronic Heart Failure

Question 1

What is CHF?

Answer 1

•Heart is not able to supply sufficient oxygen-rich blood to the body, due to impaired ability of the ventricle to either fill or eject blood

Question 2

What contributes to CHF?

Answer 2

•Damage from MI (ischemic) or from long lasting HTN (non-ischemic)

Question 3

What are the symptoms of HF?

Answer 3

•Related to fluid overload
^ SOB
^ Edema
Symptoms can occur due to problems with systolic (contraction) or diastolic (relaxation)

Question 4

What is performed when HF is suspected?

Answer 4

•Echocardiography or echo
^ Provides an estimate of LVEF: EF <40% indicates systolic dysfunction or HFrEF

EF <40%: impaired ability to eject blood during systole

Question 5

Clinical diagnosis of HF (category C)

Answer 5

•Structural and/or functional cardiac abnormality with prior or current sx;
I : No limitations of physical activity
II: Ordinary physical activity results in symptoms of HF
III: Minimal exertion causes sx of HF

Question 6

Clinical diagnosis of HF (category D)

Answer 6

•Advanced HF with severe symptoms, sx at rest or recurrent hospitalizations despite maximal treatment;
IV: Unable to carry on any physical activity without symptoms of HF, or sx of HF at rest

Question 7

Clinical diagnosis of HF (category A and B)

Answer 7

A: At risk for development of HF, but no sx, without structural heart disease or elevated biomarkers (HTN, DM, ASCVD)

B: Pre-HF; structural heart disease, abnormal cardiac function or elevated biomarkers, but without signs or sx (LVH, low EF, valvular disease)
^ No limitations of physical activity

Question 8

Labs/Biomarkers of HF

Answer 8

• Increased BNP: normal is <100
• Increased NT-proBNP: normal is <300

BNP and pro-BNP are used to distinguish between cardiac and non-cardiac causes of dyspnea

Question 9

Left-sided signs and symptoms of HF

Answer 9

• Orthopnea: SOB when lying flat

• Paroxysmal nocturnal dyspnea (PND) nocturnal SOB and cough

• Bibasilar rales: crackling lung sounds heard on lung exam

• S3 gallop: abnormal heart sound

• Hypoperfusion (renal impairment, cool extremities)

Question 10

General signs and symptoms of HF

Answer 10

• Dyspnea (SOB at rest or upon exertion)
• Cough
• Fatigue, weakness
• Reduced exercise capacity

Question 11

Right-sided signs and symptoms of HF

Answer 11

• Peripheral edema

• Ascites: abdominal fluid accumulation

• Jugular venous distention (JVD): neck vein distention

• Hepatojugular reflux (HJR): neck vein distention from pressure placed on the abdomen

• Hepatomegaly: enlarged liver due to fluid congestion

Question 12

How is Cardiac output (CO) determined?

Answer 12

• CO = HR (heart rate) X SV (stroke volume)
OR
• The volume of blood ejected from left ventricle during one complete heartbeat

*Cardiac index (CI) relates the CO to the size of tue patient;
^ CI = CO/BSA

Question 13

What are compensatory mechanisms?

Answer 13

•HFrEF is a low cardiac output state. The body compensates by:
^ Activating neurohormonal pathways to increase blood volume or the force or speed of contractions (temporarily increases CO but chronically leads to cardiac remodeling)

• The main pathway is the RAAS, the SNS and vasopressin

Question 14

RAAS and Vasopressin Activation

Answer 14

1) Ang I to Ang II by the enzyme ACE

2) Ang II cause vasoconstriction and stimulates aldosterone from adrenal gland and vasopressin from pituitary gland

3) Aldosterone: Na and water retention

4) Vasopressin: vasoconstriction and water retention

Question 15

Natural products for HF

Answer 15

• Omega-3 fatty acid
• Hawthorne and coenzyme Q10

Question 16

Drugs that cause or worsen HF

Answer 16

Most drugs cause fluid retention, edema, increase BP or have negative inotropic effects

• Dipeptidyl peptidase 4 inhibitors: Alogliptin, saxagliptin

• Immunosuppressants: TNF inhibitors (adalimumab, etanercept) and interferons

•Non-Dihydropyridine CCBs

• Antiarrythmics: class I (quinidine, flecainide) and dronedarone

• Thiazolidinediones: increases risk of edema

• Itraconazole

• Oncology drugs: anthracyclines (doxorubicin, daunorubocin)

•NSAIDs

Question 17

Tx for HF (Initial)

Answer 17

1) ACE inhibitors, ARBs or ARNI
^ decreases mortality in HFrEF
^ ARNI preferred over ACE/ARB to further reduce morbidity and mortality

2) BBs
^ provide benefit in controlling HR and reducing arrhythmia risk: decreases mortality in HFrEF

3) Loop Diuretics
^ reduce blood volume, which decreases edema and congestion; most HF pts need a loop diuretic for sx relief

Question 18

Tx for HF (secondary, add on)

Answer 18

1) ARAs
^ decreases morbidity and mortality in NYHA Class II-IV
^ provide added diuresis; improve sx and EF
^ Must meet eGFR, SCr and K criteria for use

2) SGLT2 Inhibitors
^ decreases morbidity and mortality in NYHA Class II-IV HFrEF with or without DM
^ must meet eGFR criteria for use

3) Hydralazine and nitrates (BiDil)
^ decreases morbidity and mortality in black patients in NYHA III-IV, when added to ACE/ARB and BB or in other pts who cannot tolerate an ACE or ARB

4) Ivabradine (Corlanor)
^ decreases the risk of hospitalization in pts with stable NYHA II-III HF in normal sinus rhythm with a resting HR>=70 BPM on maximally tolerated dose of BB

Question 19

Tx for HF (additional meds)

Answer 19

1) Digoxin
^ provides a small increase in CO, improves sx and decreases cardiac hospitalizations (does not decrease mortality)

2) Vericiguat, (sGC) stimulator
^ decreases the risk of hospitalization and CV death after HF hospitalization or need for IV diuretics

Question 20

Loop Diuretics - MOA

Answer 20

•Block Na and Cl reabsorption in the thick ascending limb of the loop of henle. They increase the excretion of Na, K, Mg, Ca and water.

•Decrease in fluid volume makes heart to pump easier and reduces congestive symptoms. These do not improve survival but required for symptom control

Question 21

Loop Diuretics - drugs

Answer 21

•Furosemide (Lasix)
•Bumetanide (Bumex)
•Torsemide
•Ethacrynic acid (Edecrin)

Question 22

Loop Diuretics - drug effects

Answer 22

•Warnings: sulfa allergy - does not apply to ethacrynic acid

•SEs:
^ decrease electrolytes: K, Mg, Na, Cl, Ca
^ increase electrolytes: HCO3 (metabolic alkalosis), UA, BG, TG, total cholesterol
^ ototoxicity - more with ethacrynic acid or rapid IV administration
^ orthostatic hypotension, photosensitivity

•Monitoring: renal fx, fluid status, BP, electrolytes, audiology testing, s/sx of HF

NOTES:
^ furosemide injection: store at room temperature
^ PO: furosemide 40 mg = torsemide 20 mg = bumetanide 1 mg = ethacrynic acid 50 mg
^ furosemide IV:PO ratio 1:2

Question 23

ACE Inhibitors - MOA and drugs

Answer 23

•Block the conversion of Ang I to Ang II which decreases vasoconstriction and aldosterone secretion

*Enalapril (Vasotec): 10-20 mg BID
*Lisinopril (Zestril, Privinil): 20-40 mg daily
*Quinapril (Accupril): 20 mg BID
*Ramipril (Altace): 10 mg daily
*Captopril (Capoten): TID

Question 24

ACE Inhibitors - drug effects

Answer 24

•Boxed Warnings: teratogenic

•CIs:
^ Do not use with hx of angioedema
^ Do not use within 36hrs of Entresto

•Warnings: angioedema, hyperkalemia, hypotension, renal impairment, bilateral renal artery stenosis

•Monitoring: BP, K, renal fx, s/sx of HF

Question 25

ARBs - MOA, drugs and effects

Answer 25

•Block Ang II from binding to the AT1 which decreases morbidity and mortality

*Losartan (Cozaar): 50-150 mg daily
*Valsartan (Diovan): 160 mg BID

•Less cough, less angioedema, no washout period required

•The other effects same as ACE inhibitors

Question 26

Sacubitril/Valsartan

Answer 26

•Entresto
•Drug effects are same as ACE Inhibitors
•Do not use with ACE inhibitors or ARBs

Question 27

ACE Inhibitors, ARBs and ARNI DDIs

Answer 27

•Decreases lithium clearance and increases the risk of lithium toxicity

Question 28

BBs - MOA

Answer 28

•They antagonize the effects of catecholamines (NE)
•Decreases morbidity and mortality
•Do not use BBs with ISA
•Discontinue acute decompensated HF if hypotension or hypoperfusion is present

Question 29

Beta-1 selective BBs

Answer 29

•Metoprolol succinate ER (Toprol XL)
^ target dose: 200 mg daily

•BW: do not discontinue abruptly
•Warnings:
^ caution in diabetes; can worsen hyperglycemia/hypoglycemia and mask hypoglycemic sx
^ caution with bronchospastic disease
^ caution with Raynaud’s
•SEs: bradycardia, fatigue, hypotension, dizziness, depression, impotence, Raynaud’s
•Monitoring: HR, BP, s/sc of HF

NOTES: Toprol XL can be cut in half; take with or immediately after meals

Question 30

Non-selective BB and Alpha-1 Blocker

Answer 30

•Carvedilol (Coreg, Coreg CR)
^ IR: <= 85 kg: 25 mg BID, >85 kg: 50 mg BID
^ CR: 80 mg daily

** Take with food
** Drug effects are same as Beta- selective BBs

Question 31

ARAs - MOA

Answer 31

•Works on distal convoluted tubule and collecting ducts.
•Spironolactone is non-selective which blocks androgen and exhibits endocrine side effects.
•Eplerenone is selective and does not exhibit endocrine side effects
•They decrease morbidity and mortality

Question 32

ARAs - drug and drug effects

Answer 32

•Spironolactone (Aldactone):
^ 25 mg daily or BID
•Eplerenone (Inspra)

• CIs: hyperkalemia, severe renal impairment, Addison’s disease
• Warnings: do not initiate for HF if K>5 mEq/L
• SEs: hyperkalemia, increased SCr, dizziness
  ^ Spironolactone: gynecomastia, breast tenderness, impotence
• Monitoring: BP, K, renal fx, s/sx of HF

Question 33

ARA DDIs

Answer 33

•Decreases lithium clearance and increases lithium toxicity

Question 34

Hydralazine/Nitrates - MOA

Answer 34

•Hydralazine: direct arterial vasodilator which decreases afterload
•Nitrates: causes venous vasodilation and decreases preload
•The combination improves survival bit to a lesser degree than ACE and ARBs
•Alternative for those who can’t tolerate ACE and ARBs
•BiDil is indicated in black pts with NYHA class III or IV who are symptomatic despite optimal tx

Question 35

Hydralazine/Nitrates - drug effects

Answer 35

Hydralazine/ Isosorbide Dinatrate (BiDil)

•Hydralazine:
^ Warning: DILE
^ SEs: peripheral edema/headache/ flushing/palpitations/reflex tachycardia

•Isosorbide dinitrate:
^ CIs: PDE-5 inhibitors
^ SEs: hypotension, headache, dizziness, lightheadedness, flushing, tachyphylaxis (need 10-12 hr nitrate-free interval), syncope

Question 36

SGLT2 Inhibitors

Answer 36

• Decreases mortality

•Dapagliflozin (Farxiga): eGFR <30; do not initiate
•Empagliflozin (Jardiance): eGFR<20; do not initiate

• Warnings:
  ^ ketoacidosis, hypotension, AKI, mycotic infections
• SEs: weight loss, thirst, urination

Question 37

Digoxin - MOA

Answer 37

•Inhibits the Na-K-ATPase pump, causing positive inotropic effect (increases CO) and negative chronotropy (decrease HR)

•It doesn’t improve survival, but reduce HF related hospitalizations

•It is added to mortality-reducing drugs to improve sx, exercise tolerance and quality of life

•Lowe dose if renal insufficiency, smaller, older or female

Question 38

Digoxin - drug effects

Answer 38

•Digoxin (Digitek, Digox, Lanoxin)
^ typical: 0.125-0.25 mg PO daily
^ CrCl <50: lower dose or frequency

• Lower dose by 20-25% when switching from PO to IV
• Therapeutic range: 0.5-0.9 ng/mL

•Monitoring: electrolytes, renal fx, HR
•Toxicity:
^ initial s/sx: N/V, loss of appetite and bradycardia
^ severe s/sx: blurred/double vision, greenish-yellow halos

Antidote: DigiFab

Question 39

Digoxin - DDIs

Answer 39

•Use caution with other drugs that decreases HR (BBs, non-DHP CCBs, amiodarone)
•Hypokalemia, hypomagnesemia and hypercalcemia increases the risk of digoxin toxicity
•Digoxin is a substrate of P-gp
^ decrease dose by 50% when starting amiodarone

Question 40

Ivabradine (Corlanor)

Answer 40

•Decreases HR, reduced hospitalizations but does not affect mortality
•Used when sinus rhythm with a resting HR >=70 BPM

Target: 50-60 BPM

Warnings: bradycardia, increases the risk of QT prolongation and ventricular arrhythmias

SEs: bradycardia, hypertension, Afib

Question 41

Vericiguat (Verquvo)

Answer 41

•Soluble guanylte cyclase stimulator
•Do not use with riociguat
•SEs: hypotension

Question 42

Potassium oral supplements

Answer 42

•Potassium should be checked with changes in renal fx and after any change in diuretic, ACE, ARB or ARA dose
•Magnesium should be checked and corrected prior to correcting the K level
•PO solution 10% (20 mEq/15 mL)

Question 43

Potassium Chloride

Answer 43

1) ER capsules:
^ Micro-K, Klor-Con sprinkle; can be sprinkled on small amount applesauce or pudding

2) ER tablets:
^ K-tab, Klor-con; swallow whole, do not chew, crush, cut or suck on the tablet
^ Klor- Con M; it can be cut in half or dissolved in water (stir for 2 min and drink immediately). Do not chew, crush or suck

3) Oral packet:
^ dissolve contents in water and drink asap

4) Oral solution:
^ KCl 10% = 20 mEq/15 mL
^ mix each 15 ml with 6 oz of water