Heart Failure lecture pt 1

Question 1

1) Define heart failure
2) Pharmacotherapeutic indications and goals of therapy for HF are dependent on what?

Answer 1

1) Structural or functional impairment of ventricular diastole (filling) & / or ventricular systole (contraction)
2) Stage, classification and left ventricular function, & other patient-specific factors
-Stages: A / B / C / D
-Classes: I / II/ III / IV
-HFrEF, HFimpEF, HFmrEF and HFpEF

Question 2

List and describe the 4 main types of HF

Answer 2

1) HFrEF = heart failure with reduced ejection fraction
2) HFimpEF = heart failure with improved ejection fraction
3) HFmrEF = heart failure with mildly reduced ejection fraction
4) HFpEF = heart failure with preserved ejection fraction

Question 3

Epidemiology:
1) Less than ________ million American adults have HF
2) 5-year mortality rate is what?

Answer 3

1) 10 (5.7-6.5)
2) 42% to 50%

Question 4

Etiology of HF:
1) ________________ is the most common cause of HFrEF, accounting for up to 75% of cases.
2) ________ remains an important cause and/or contributor to both HFrEF and HFpEF in many patients

Answer 4

1) Coronary artery disease (CAD)
2) HTN

Question 5

List beneficial and detrimental effects of the following compensatory mechanism: increased preload (through Na+ and retention)

Answer 5

1) Benefit: Optimizes stroke volume via frank-starling mechanism
2) Detriments: Pulmonary and systemic congestion and edema formation
-Increased MVO2

Question 6

List beneficial and detrimental effects of the following compensatory mechanism: vasoconstiction

Answer 6

1) Benefits: Maintains BP in face of reduced CO
-Shunts blood to brain and heart
2) Detriments: Increased MVO2; increased afterload decr. stroke vol. and further activates the compensation

Question 7

List beneficial and detrimental effects of the following compensatory mechanism: tachycardia and increased contractility (due to SNS activation)

Answer 7

1) Beneficial: Helps maintain CO
2) Detrimental: Increased MVO2
-Precipitation of ventricular arrythmias
-Increased risk of myocardial death

Question 8

List beneficial and detrimental effects of the following compensatory mechanism: ventricular hypertrophy and remodeling

Answer 8

1) Beneficial: Helps maintain CO
-Reduces myocardial wall stress
-Decreases MVO2
2) Diastolic + systolic dysfunct.
-Incr. risk of myocardial cell death + ischemia
-Incr. arrhythmia risk fibrosis

Question 9

Increasing afterload causes a ___________ in SV

Answer 9

decrease

Question 10

What is the pathophys behind Heart failure with preserved ejection fraction?

Answer 10

Impaired myocardial relaxation and/or increased diastolic stiffness

Question 11

What is the pathophys behind Heart failure with reduced ejection fraction?

Answer 11

Persistent decline in CO in HF triggers long-term activation of compensatory responses

Question 12

Heart failure with reduced ejection fraction: tachycardia and increased contractility occurs due to what?

Answer 12

Norepinephrine

Question 13

Heart failure with reduced ejection fraction: Fluid retention and increased preload is due to what?

Answer 13

Activation of renin-angiotensin-aldosterone system (RAAS)

Question 14

Heart failure with reduced ejection fraction: Vasoconstriction and increased afterload causes what?

Answer 14

↓ CO

Question 15

Heart failure with reduced ejection fraction:
Ventricular hypertrophy and remodeling leads to what?

Answer 15

Decreases in mechanical performance of the heart, increases regurgitant flow through the mitral valve, and, in turn, fuels the continued progression of remodeling

Question 16

Amyloid cardiomyopathy:
1) What is the most common protein?
2) What is used to treat this condition?

Answer 16

1) Transthyretin (TTR)
2) Tafamidis meglumine (Vyndamax)

Question 17

Aldosterone: What 2 roles does it play in heart failure?

Answer 17

1) Aldosterone-mediated sodium retention leads to volume overload and edema
2) Produces interstitial cardiac fibrosis through increased collagen deposition in

Question 18

Natriuretic peptides: What does BNP do in HF?

Answer 18

Concentrations are elevated in patients with HF functioning to increase natriuresis and diuresis and attenuate activation of the RAAS and SNS

Question 19

Arginine vasopressin (AVP) a.k.a. antidiuretic hormone (ADH):
1) What is it?
2) Name 2 drugs that affect it

Answer 19

1) Peptide hormone that regulates renal water excretion and plasma osmolality
2) Drugs > tolvaptan & conivaptan

Question 20

List 2 factors that precipitate HF

Answer 20

1) MI
2) Uncontrolled hypertension

Question 21

Acute decompensated HF has 4 hemodynamic subsets based on volume status, which are what?

Answer 21

1) Euvolemic or “dry”
2) Volume overloaded or “wet”
3) Adequate CO or “warm”
4) Hypoperfusion or “cold”

Question 22

Describe nonpharmacologic Tx of HF

Answer 22

1) Mild (<3 g/day) to moderate (<2 g/day) sodium restriction
2) Daily measurement of weight

Question 23

Stage A (at risk for HF) has no structural heart disease or HF symptoms but are at high risk for developing HF; describe Tx

Answer 23

Risk factor identification and modification

Question 24

“Cardiac disease (e.g., structural heart disease) but do not have HF symptom” describes what stage of HF?

Answer 24

Stage B HF

Question 25

Define stage C HF

Answer 25

Structural heart disease and previous or current symptoms

Question 26

Stage C w. HFrEF < = 40%: 1) When should you Tx with hydralazine / isosorbide? 2) List 2 other meds that should be used in this stage

Answer 26

1) NYHA III-IV + African American / Black American 2) Mineralocorticoid receptor antagonist (MRA) + Diuretics (PRN)

Question 27

Thiazide diuretics: 1) MOA? 2) Amt of diuresis? 3) Give an example

Answer 27

1) Block sodium reabsorption in the distal convoluted tubule 2) Weaker diuresis compared to loops 3) Hydrochlorothiazide (HCTZ)

Question 28

Loop diuretics 1) Induce a _______________-mediated increase in renal blood flow, which contributes to their natriuretic effect 2) What can decrease efficacy?

Answer 28

1) prostaglandin 2) NSAIDS can block prostaglandin-mediated effect and can diminish diuretic efficacy

Question 29

stopped before slide 58

Question 30

Explain why kidney function may be an issue with ACEi / ARBs for HF

Answer 30

1) ANG II maintains perfusion of efferent arteriole and inhibiting this may cause increases in serum creatinine 2) Either modest elevations of ≤30% (for baseline creatinine values ≤3 mg/dL) or absolute increases <1 mg/dL do not warrant changes

Question 31

Describe the basics of dosing ACEis/ARBs for HF

Answer 31

1) Start low and titrate by doubling the dose every 2 weeks 2) Monitoring: blood pressure, renal function, and serum potassium should be evaluated at baseline and within 1 to 2 weeks after therapy is started [and after each dose increase]

Question 32

ACEis/ ARBS: 1) List the adverse effects 2) What are the contraindications?

Answer 32

1) Angioedema, hyperkalemia, hypotension, renal dysfunction -ACEi: cough 2) Bilateral renal artery stenosis, history of angioedema, or pregnancy (teratogenic) -ARBs can be used cautiously in patients with a Hx of ACEi induced angioedema

Question 33

ANRIs ((Valsartan / sacubitril (Entresto)): 1) When do guidelines recommend replacing an ACEi or ARB with an ARNI? Why? 2) What is there a significant reduction in compared to enalapril?

Answer 33

1) In patients with HFrEF and NYHA class II-III symptoms tolerating an ACE inhibitor or ARB; to further reduce morbidity and mortality 2) Mortality and first hospitalization compared to enalapril (PARADIGM-HF)

Question 34

How do you dose Valsartan / sacubitril (Entresto) (an ANRI)

Answer 34

1) 49/51 mg sacubitril/valsartan twice daily and titrated to the target dose of 97/103 mg sacubitril/valsartan twice daily after 2 to 4 weeks 2) Reduced dose of 24/26 mg sacubitril/valsartan is available for patients taking a low dose of either an ACE inhibitor or an ARB prior to initiation or those with severe renal dysfunction (eGFR <30 mL/min/1.73m2)

Question 35

Valsartan / sacubitril (Entresto) (ANRI): 1) What are the adverse effects? 2) What are the contraindications?

Answer 35

1) Angioedema, hyperkalemia, hypotension, dizziness, renal dysfunction. 2) Hx of angioedema associated with ACE inhibitor or ARB therapy or pregnancy

Question 36

List and describe 3 beta blockers used for HF

Answer 36

1) Metoprolol succinate ER (Toprol XL): Can cut ER tablet in half 2) Carvedilol (Coreg) 3) Bisoprolol (Zebeta): Not approved by the Food and Drug Administration (FDA) for use in HFrEF

Question 37

Describe the basics of dosing Beta blockers for HF

Answer 37

1) Generally start ACEi/ARB first 2) Do not start β-Blockers during acute decompensation 3) β-Blocker doses should be doubled no more often than every 2 weeks

Question 38

List some adverse effects/ contraindications for beta blockers

Answer 38

Bradycardia, heart block, bronchospasm, hypotension, worsening HF

Question 39

Aldosterone antagonists: 1) What is the MOA? 2) Do they help prevent hospitalization or are they just for Sx?

Answer 39

1) Inhibit renal sodium reabsorption 2) Significantly reduce the risk of mortality and hospitalization

Question 40

What are 3 situations in which you should avoid using aldosterone antagonists?

Answer 40

1) Baseline potassium is >5 mEq/L 2) Serum creatinine > 2 mg / dL (women) to > 2.5 mg /dL (men) 3) CrCl < 30 mL /min

Question 41

Aldosterone antagonists: 1) Concomitant NSAIDs may increase the risk of ______________. 2) Concomitant diuretic non-adherence may increase the risk of _________________. 3) Diarrhea may be early sign of ________________.

Answer 41

1) hyperkalemia 2) hyperkalemia 3) hyperkalemia

Question 42

List the adverse effects of aldosterone antagonists

Answer 42

Gynecomastia/breast tenderness/menstrual irregularities (spironolactone), hyperkalemia, worsening renal function

Question 43

Give the MOAs for: 1) Nitrates 2) Hydralazine

Answer 43

1) Nitric oxide donors for venodilation 2) direct-acting arterial vasodilator

Question 44

Hydralazine / isosorbide dinitrate (BiDil) is very effective for what population?

Answer 44

African Americans / Black Americans

Question 45

Ivabradine (Corlanor): 1) What is the MOA? 2) Reduces the risk of hospitalization for worsening HF in patients with ___________ in sinus rhythm

Answer 45

1) Selectively inhibits the cardiac pacemaker current responsible for controlling the depolarization rate of the sinus node 2) HFrEF

Question 46

Ivabradine (Corlanor): 1) What should you do after 2 wks of Tx? 2) If the heart rate is >60 bpm, the dose can be increased to a maximum of ______ mg BID

Answer 46

1) The resting heart rate should be evaluated, and if between 50 and 60 bpm, the dose [5 mg PO BID w/ meals] should be continued 2) 7.5 mg BID

Question 47

Ivabradine (Corlanor): 1) If at any point, the heart rate is <50 bpm or if the patient has symptomatic bradycardia, the dose should be reduced by _____ mg BID. 2) If the patient is receiving only ______ mg BID, then ivabradine should be discontinued

Answer 47

1) 2.5 mg BID 2) 2.5 mg BID

Question 48

Digoxin: 1) What is the MOA? 2) Who does it benefit in trials? 3) Is it a first line agent?

Answer 48

1) Increases parasympathetic activity in HF patients 2) HFrEF = decreased hospitalizations HFpEF = no benefit 3) Digoxin is not considered a first-line agent in HF

Question 49

Serum digoxin concentrations (SDCs) of _______ to ______ ng/mL 1 month after initiation were associated with lower mortality, all-cause hospitalizations, and HF hospitalization

Answer 49

0.5 to 0.9

Question 50

What are the adverse effects of digoxin?

Answer 50

GI and CNS adverse effects, brady- and tachyarrhythmias

Question 51

1) How do you Tx Digoxin toxicity? 2) In patients with life-threatening digoxin toxicity, purified _______________________ antibody fragments should be administered.

Answer 51

1) Usual treatment includes drug withdrawal or dose reduction 2) digoxin-specific Fab

Question 52

Calcium channel blockers, Tafamidis: What is the MOA?

Answer 52

Stabilizes the TTR tetramer and halts the amyloid deposition process

Question 53

HTN + HF: 1) Calcium channel blockers with negative inotropic effects (e.g., verapamil, diltiazem) should be avoided in patients with _________. 2) In patients with _______, both verapamil and diltiazem can be safely used

Answer 53

1) HFrEF 2) HFpEF

Question 54

Angina + HF: 1) What are 2 effective antianginals? 2) Is amlodipine safe?

Answer 54

1) Nitrates and β-blockers 2) Yes

Question 55

Atrial fibrillation + HF: 1) ____________ are more effective than digoxin and have the added benefits of improving morbidity and mortality in patients with HFrEF. 2) Combination therapy with ___________ and a β-blocker may be more effective for rate control than either agent used alone

Answer 55

1) β-Blockers 2) digoxin

Question 56

Atrial fibrillation + HF: 1) Calcium channel blockers with negative inotropic effects such as ___________ or __________ should be avoided in patients with HFrEF but are effective in patients with HFpEF 2) What 2 other drugs appear safe for AFIB and HFrEF?

Answer 56

1) verapamil or diltiazem 2) Amiodarone (Pacerone) and dofetilide (Tikosyn)

Question 57

Diabetes + HF: 1) Because the TZDs (i.e., pioglitazone) are associated with _________________, these medications should not be used in patients with NYHA class II-IV HF. 2) In patients with HFrEF and NYHA class II-IV symptoms, both __________________ and _________________ reduced the risk of worsening heart failure and cardiovascular death

Answer 57

1) fluid retention 2) dapagliflozin (Farxiga) and empagliflozin (Jardiance)

Question 58

Potassium chloride (KCl) (Klor-Con): 1) What are some side effects? 2) What drug groups does it interact with? Why? 3) What may you see pts taking?

Answer 58

1) GI irritation, diarrhea, hyperkalemia 2) Anticholinergics; may decrease gastric motility and increase the transit time of solid oral dosage forms of KCl therefore causing GI mucosal injury 3) You will see patients taking ACEi, spironolactone and potassium

Question 59

Potassium chloride (KCl) (Klor-Con): 1) What are some side effects?

Answer 59

1) GI irritation, diarrhea, hyperkalemia

Question 60

Name a drug that was FDA-approved May 26, 2023?

Answer 60

Inpefa (sotagliflozin)