Exam 2: Heart Failure Flashcards
Do patients with heart failure tend to have high or low blood pressures?
Low BP
-because cardiac output is low
What is the cardinal sign of heart failure?
Edema
What are the 2 most common causes of heart disease?
CAD
Chronic hypertension
What are the survival rates associated with heart failure?
5 years : about 50%
What is Heart Failure?
An abnormality of myocardial function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues
-Not a single disease state, but the final common pathway for CV diseases
What are the 2 most common reasons why people die relating to heart failure?
Arrythmia
Pump Failure
What 2 non-cardiac factors does Entresto work on?
-Endothelial dysfunction
-Neurohormonal activation
What 4 factors contribute to Left Ventricular Dysfunction?
CAD
HTN
Cardiomyopathy
Valvular disease
How does Left Ventricular Dysfunction lead to death?
LV dysfunction -> Remodeling -> Decreased EF -> Death
What is the only effective cure for heart failure?
Heart transplant
What are the 5 types of heart failure?
Asymptomatic reduced EF
HFrEF (HF with reduced ejection fraction)
HFpEF (HF with preserved ejection fraction)
HFmrEF (Heart failure with mildly reduced ejection fraction)
HFimpEF (Heart failure with improved ejection fraction)
What is the definition of HFrEF?
HF symptoms with EF <40%
If a patient has an EF < 40% but is not experiencing symptoms, what do they have?
Asymptomatic reduced EF
What is the definition of HFpEF?
HF symptoms with EF > 50%
What impairment in cardiac function is caused by HFrEF?
Systolic dysfunction: decreased contractility
What impairment in cardiac function is caused by HFpEF?
Diastolic dysfunction: impairment in ventricular relaxation/filling
(inability of heart to fill/relax)
*note: many patients have a combination of systolic and diastolic dysfunction
What is the cause of HFrEF?
Dilated ventricle (dilated cardiomyopathy)
(CAD)*
What is the most common cause of HFpEF?
Hypertension
What is the definition of HFmrEF?
Heart failure with mildly reduced ejection fraction
EF: 41-49%
What is the definition of HFimpEF?
Heart failure with improved ejection fraction
Improved EF > 40%, previously had HFrEF
What are the 3 determinants of Left-Ventricular Performance (Stroke-Volume)?
Preload
Myocardial Contractility
Afterload
What makes up preload?
Venous return
LV end-diastolic volume
What makes up Myocardial Contractility?
Force generated at any given left ventricular end diastolic volume (LVEDV)
What makes up Afterload?
Aortic impedance
Wall stress
True or False:
As preload increases, stroke volume increases
True
(the more volume you put in, the more the sarcomeres stretch causing the force of blood exiting to be stronger)
(think of a balloon)
What factors cause the heart to remodel?
Increased pressure
Extra fluid
(remodels to try and increase efficiency of pumping blood)
True or False:
Some drugs that decrease afterload may increase stroke volume
True
On a Frank-Starling curve, what drug is able to move a patient down and to the left? (decrease stroke volume and LVEDP [preload])?
*decreases preload is why it is good
Diuretics
(reduce fluid)
*gets patient out of pulmonary congestion
How do we estimate afterload?
Blood pressure
In a patient with heart failure, how does increasing afterload affect stroke volume?
Greatly decreases it
(in a normal patient, it would not have an effect unless the afterload was very greatly increased)
Decreased cardiac output leads to decreased blood pressure + organ perfusion which ultimately leads to increases in what 5 things?
SNS *bad
RAAS *bad
Vasopressin *bad
Atrial natriuretic peptides (ANP) *good
Brain natriuretic peptides (BNP) *good
What do increases in the SNS, RAAS, and Vasopressin lead to?
Cell death/fibrosis
Arrythmias
(catecholamines released from the SNS predispose patients to arrythmias)
Reduced cardiac output
Vasoconstriction
What causes increased preload in HF?
Na/Water retention
What is the main reason why patients develop heart failure exacerbations?
Lack of compliance with drugs or diet
What are the negative inotropes that can induce heart failure?
Antiarrhythmics (disopyramide, flecainide)
Beta-Blockers (atenolol, propranolol, metoprolol)
CCBs (verapamil, diltiazem)
Itraconazole
What are the direct cardiac toxins that can induce heart failure?
Doxorubicin, Epirubicin, Daunomycin
CYP
Trastuzumab, Bevacizumab
5-FU
Blue Cohosh
Imatinib, Lapatinib, Sunitinib
Ethanol**, Cocaine, Amphetamines
What are the drugs that cause sodium + water retention that can also cause heart failure?
Glucocorticoids
Androgens, Estrogens
NSAIDs, COX-2 inhibitor
Rosiglitazone, Pioglitazone
Sodium containing drugs (DiNa+ containing)
What are the signs/symptoms of Right Ventricular Failure?
*Systemic venous congestion (fluid backed up in right side of heart)
Signs:
*Peripheral edema
*JVD
HJR
*Hepatomegaly
Ascites
Symptoms:
Abdominal pain
Anorexia
Nausea
Bloating
Constipation
What are the signs and symptoms of Left Ventricular Failure?
*Pulmonary congestion
(fluid in lungs)
Signs:
*Rales
*S3 gallop
*Pulmonary edema
Pleural effusion
Cheyne-stokes respiration
Symptoms:
*DOE
*Orthopnea
*PND
Tachypnea
*Bendopnea
Cough
Hemoptysis
Failure of which ventricle involves pulmonary congestion?
Left ventricular failure
(fluid in lungs)
Failure of which ventricle involves systemic venous congestion?
Right ventricular failure
(fluid backed up in right side of heart/systemic)
What are the 6 major signs of pulmonary congestion (left ventricular failure)?
Exertional dyspnea (SOB w/ exertion)
Orthopnea (SOB when lying down, quantified by pillow number used to sleep)
Paroxysmal nocturnal dyspnea (PND) (SOB at night, feelings of suffocation/ drowning)
Rales (rattling of air through liquid in lungs)
Pulmonary edema (fluid in lungs, wispiness)
Bendopnea (SOB when bent over)
What are the 4 major signs of systemic venous congestion (right ventricle failure)?
-Peripheral edema
-Jugular vein distension (JVD) (estimate of amount of fluid in right venous circulation)
-Hepatojugular reflux (HJR) (fluid from liver goes into jugular vein when pushed)
Hepatomegaly, ascites (tap on side of stomach and see fluid wave)
How does CAD cause HF?
Scar tissue forms and does not move like regular skin (more fibroblasts)
-does not contract anymore
*we do not regenerate heart tissue
-initiates remodeling of ventricle that leads to dysfunction
Why does hypertension cause HF?
Increased pressure causes the heart to remodel itself to try and overcome it
Why should we assess natriuretic peptides with HF?
Can be used to rule out other cardiac causes of dyspnea and point towards a diagnosis of HF
What are the 2 natriuretic peptides that we should assess?
BNP
NT-proBNP
What level of BNP points to heart failure?
> 35 pg/mL
What level of NT-proBNP points to heart failure?
> 125 pg/mL
What is the main laboratory assessment we want to do on patients with HF?
Evaluation of LV function and measurement of ejection fraction (EF)
*LVEF allows us to diagnose what type of HF it is
What are the 4 ways we can measure LV function and EF?
-Echocardiogram
-Nuclear testing
(MUGA: multi-gated acquisition scanning is the gold standard***)
-Cardiac catheterization
-MRI and CT
What patients classify as NYHA Functional Class 1?
Patients with cardiac disease but no limitations of physical activity
What patients classify as NYHA Functional Class 2?
Patients with cardiac disease with slight limitations of physical activity
(slight symptoms)
What patients classify as NYHA Functional Class 3?
Patients with cardiac disease with limitations of physical activity
(symptoms with moderate activity)
What patients classify as NYHA Functional Class 4?
Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort
(symptoms at rest)
What patients classify as AHA Stage A?
*High risk of developing HF
-No identified structural or functional abnormalities
-Have never shown signs or symptoms of HF
(HTN, CAD, DM, etc)
What patients classify as AHA Stage B?
Structural heart disease that is strongly associated with HF but NO SIGNS OR SYMPTOMS of HF
(stage 1 patients)
What patients classify as AHA Stage C?
Current or prior symptoms of HF
-Associated with underlying structural heart disease
What patients classify as AHA Stage D?
Advanced structural heart disease + marked symptoms of HF AT REST
*despite maximal medication therapy and who require specialized interventions
What NYHA classes and AHA stages line up with each other?
A - none (high risk, no HF yet)
B - 1 (asymptomatic)
C - 2, 3 (symptoms w/ mod exertion)
D - 4 (symptoms at rest)
What is the definition of Asymptomatic rEF?
No heart failure symptoms with EF < 40%
*AKA Asymptomatic LV systolic dysfunction
What is the definition of HFrEF?
Heart failure symptoms with EF < 40%
What is the definition of HFimpEF?
Previous symptoms of rEF now improved
What is the definition of HFmrEF?
Heart failure symptoms with EF 41-49%
How should exercise be recommended to HF patients?
-Recommend regular exercise (walking + cycling) for all patients with stable HF
-Dynamic exercises to increase HR to 60-80% of maximum for 20-60 minutes 305 times/week
**use caution during acute symptoms
What 3 dietary changes should be made in HF patients?
Sodium: restrict to 2-3 g/day
Alcohol: In EtOH induced HF need to abstain, otherwise no more than 2 drinks/day for men or 1 for women
Fluid intake: Restrict < 2 L/day in patients with hyponatremia (<130 mEq/L) or fluid volume is difficult to maintain with diuretics
What sodium level indicates hyponatremia?
< 130 mEq/L
What are the general measures that should be taken in HF patients?
-Weight monitoring
-Education of patients + families
*Smoking cessation
-Immunizations
-Replace electrolytes
-Thyroid disease management
-Herbal products (may help)
What are the 4 strategies to target in HF with drugs?
-Reduce intravascular volume
-Increase myocardial contractility
-Decrease ventricular afterload
-Neurohormonal blockade
What drugs reduce intravascular volume?
Diuretics
SGLT2i
What drugs increase myocardial contractility?
Positive inotropes
What drugs decrease ventricular afterload?
ACEi
vasodilators
SGLT2i
What drugs cause a neurohormonal blockade?
ARNIs
Beta blockers
ACEIs
ARBs
MRAs
SGLT2i
What drugs should be used in Stage A HF?
ACEi/ARB
(if atherosclerotic vascular disease is present)
What drugs should be used in Stage B HF?
ACEi/ARB
Beta Blocker
(if previous MI or asymptomatic rEF)
What are the 4/5 initial drugs to initiate for stage C/D HF?
ARNi (II-II)/ ACEi or ARB (II-IV)
Beta blocker
MRA
SGLT2i
Diuretic **prn (loop preferred)
If a stage C patient is started on the big 4 and their LVEF improves to > 40% (HFimpEF) what do you do?
Continue the big 4 with serial reassessment and optimize dosing
-assess adherence and patient education
-address goals of care
If a stage C patient is started on the big 4 but their LVEF stays at or below 40%, what do you do?
Class 3,4 and African American:
Hydralazine/ Isosorbide Dinitrate
Class 1-3, LVEF <or = 35%:
ICD (implantable cardioverter-defibrillator)
Class 2-3, Ambulatory IV, LVEF < or = 35%, NSR and QRS > or = 150 ms with LBB:
CRT-D (cardiac resynchronization therapy)
When is ISDN/Hydralazine used?
Select patients:
-African American patient with continuing symptoms after receiving the big 4
-If ARNI/ACEI/ARB intolerant
When is Digoxin given?
If persistently symptomatic on big 4
Who should receive diuretics?
All HF patients with signs/symptoms of FLUID RETENTION
(SYMPTOMATIC patients)
Do diuretics reduce mortality?
NO, only reduce hospitalizations
What are the 3 benefits that diuretics provide?
-Reduce symptoms of fluid overload
-Improve exercise tolerance
-Improve QOL
What dose of diuretics should patients be put on?
Lowest dose that maintains euvolemia
(LOWEST DOSE POSSIBLE to achieve steady state)
True or False: patients who do not have symptoms of volume overload should not receive diuretics
TRUE
(could imbalance electrolytes)
How do we determine the fluid status of a person?
By weighing them
What is the MOA of diuretics?
-Increase sodium + water excretion by reducing sodium reabsorption in the nephron
**Reduce preload and cardiac filling pressure
Diuretics must be able to get to their site of action to elicit a response, what does this mean/ where is their site of action?
Work in the KIDNEYS!
*Must note that patients with HF often have a hard time perfusing their kidneys
Where/How do loop diuretics work?
Thick ascending loop of henle
*This is responsible for 25% of sodium reabsorption
*Loops block the Na and Cl reabsorption here
*Downstream of this, only 5-15% of sodium is reabsorbed so it is not able to make-up for this blockage
What 3 diuretics are the most potent?
Loop
Thiazides
Thiazide-like diuretics
What is an additional benefit of loop diuretics?
Enhance renal release of prostaglandins
(increases renal blood flow + enhances renal capacitance)
What drug class blocks the action of loop diuretics?
NSAIDs
**do not use in HF because of this
What are the 4 loop diuretics that can be used?
Furosemide
Bumetanide
Torsemide
Ethacrynic acid (***patients with sulfa-allergy)
What is an advantage of Torsemide over Furosemide?
Furosemide has erratic bioavailability
-torsemide may have advantage in some patients
What is the initial oral dose + usual dose range of Furosemide?
In: 20-40 mg QD or BID
Us: 20-160mg QD or BID
What is the initial oral dose+ usual dose range of Bumetanide?
In: 0.5-1mg QD or BID
Us: 1-2 mg QD or BID
What is the initial oral dose + usual dose range of Torsemide?
In: 10-20 mg QD
Us: 10-80 mg QD
What is the initial oral dose of ethacrynic acid?
25-50 mg QD or BID
What are the IV equivalent doses of Furosemide-Bumetanide-Torsemide-Ethacrynic Acid?
F 40mg = B 1mg = T 20mg = E 50mg
*note: these are also all the upper bound amounts for the initial oral dosing of the medications
*KNOW
What is an important thing to consider with Bumetanide dosing?
Has good oral bioavailability, use same IV dose as oral dose
Which one of the following doses would be considered “equivalent” to 1 mg PO bumetanide?
A. Furosemide PO 80 mg
B. Furosemide IV 20 mg
C. Torsemide PO 10 mg
D. Bumetanide IV 0.5 mg
A. Furosemide PO 80 mg
*note: bumetanide bioavailability is the same in both po and IV
*IV F 40mg = IV B 1mg
*Have to multiply F IV dose by 2 for PO dosing
When would we use thiazide and thiazide-like diuretics?
In patients with mild HF and small amounts of fluid retention
As an add-on to loop diuretics when resistant
How are thiazides affected by renal function?
*Lose effectiveness as renal function decreases (like all diuretics)
-Higher doses necessary when GFR is < 30mL/min
True or False: Thiazides are used in combination with loop diuretics in patients who become resistant to single-drug therapy
TRUE
What are the thiazide diuretics used in HF?
HCTZ **common
Metolazone **common
Chlorthalidone
CTZ (IV)
Indapamide
What are initial and max doses of HCTZ?
In: 25 mg/day
Max: 100 mg/day
What are the initial and max doses of Metolazone?
In: 2.5 mg/day
Max: 10 mg/day
What are the initial and max doses of Chlorthalidone?
In: 12.5-25 mg/day
Max: 50 mg/day
What are the adverse effects of Thiazides and Loop diuretics?
-Decrease Mg
-Decrease K
-Decrease Na
-Increase or Decrease Ca (loop decrease)
-Volume depletion, decrease renal function, pre-renal azotemia
*Postural hypotension
-Increase Uric Acid
When dosing loop diuretics, what is the target weight loss per day?
1-2 pounds/day
(1 L of fluid)
What are the 3 indicators of volume depletion?
-Increased SeCr
-Increased BUN/Cr ratio
-Hypotension
What is a normal BUN and Cr?
BUN: 10-20
Cr: 1
**a ratio greater than 20/1 indicates dehydration
How do you dose loop diuretics?
Start at low dose and double based on weight loss and diuresis
When/what should you monitor loop diuretics?
1-2 weeks after initiation or increase
-Fluid intake
-Urinary output
-Body weight
-S/s of congestion or JVD
-BP
-Electrolytes (K and Mg)
-Renal function
When do we replace K during treatment?
If K < 4, replace to > or = 4.0 mEq/L
When do we replace Mg during treatment?
If Mg < 2, replace to > or = 2.0 mEq/L
What stage patients should receive diuretics?
Stage B: No, unless they have hypertension or rEF and use HCTZ already
Stage C: Everybody with symptoms gets lowest dose possible
What are the 3 types of RAS inhibitors?
ARNi
ACEi
ARB
Why do we want to block the RAAS system?
-Enhances hypertrophy of cardiac cells
-Cell death
-Fibrosis
-Arrhythmias
Who should receive ACEi?
ALL HF PATIENTS
-regardless or type or severity of disease
What is the MOA of ACEi?
Block the conversion of Angiotensin I to Angiotensin II
*however, this can still happen by a non-specific pathway but it is substantially lower
Also prevent the degradation of bradykinin
*this is what causes the cough side effect!
(think of ACEi as dual vasodilator, venous and arterial effects)
What are the 3 most commonly used ACEi in HF and what is the TARGET DOSING of each that equal each other?
Enalapril 20mg = Captopril 150mg = Lisinopril 20 mg
What is the initial and target dosing of Enalapril?
In: 2.5-5 mg BID
Targ: 10 mg BID (20)
What is the initial and target dosing of Captopril?
In: 6.25-12.5 mg TID
Targ: 50 mg TID
What is the initial and target dosing of Lisinopril?
In: 2.5-5 mg QD
Targ: 20-40 mg QD
In patients with CrCl<30 OR Serum Creatinine > 3, how do we adjust mortality dosing?
Target dose should be 1/2 of the mortality dose for that drug
How should we titrate ACEi?
Start low and double every 1-4 weeks until target dose is reached
In what patients should we use caution when prescribing ACEi?
Volume depleted
SBP < 80
K > 5
SeCr > 3
What serum creatinine level is considered high (bad)?
> 3
*requires ACEi dose adjustment
What are the contraindications for ACEi?
-Pregnancy
-Angioedema or hypersensitivity
-Bilateral renal artery stenosis (atherosclerosis in both arteries leading to kidneys)
-Well-documented intolerance (symptomatic hypotension, decline in renal function, hyperkalemia, cough)
What should we monitor when starting ACEi?
-Volume status
-Renal function
-Potassium
-SeCr (rise expected, <30% is ok)
-Blood pressure
When should we monitor renal function and K levels with ACEi?
Prior to therapy
1-2 weeks after each dose increase
3-6 month intervals
When other treatments added that may decrease renal function
Patients with history of renal dysfunction
When starting an ACEi, what level of SeCr RISE is acceptable?
<30%
What are the side effects of ACEi?
-Hypotension
-Functional renal insufficiency
-Hyperkalemia
-Skin rash and dysgeusia (captopril)
-Cough
-Angioedema
What is the MOA of ARBs?
Directly antagonize the effects of Angiotensin at the Angiotensin 2 receptor
*no effect on bradykinin but more blockade of angiotensin
What are the 3 main ARBs used in HF?
Losartan (Cozaar)
Valsartan (Diovan)
Candesartan (Atacand)
What is the initial and target dosing of Losartan?
In: 25-50 mg QD
Targ: 150 mg QD
What is the initial and target dosing of Valsartan?
In: 20-40 BID
Targ: 160 BID
What is the initial and target dosing of Candesartan?
In: 4 mg QD
Targ: 32 mg QD
When would we use an ARB?
-Already on it for another reason
-ACEi induced cough
-ACEi induced angioedema (carefully monitor)
What is the MOA of Angiotensin Receptor Neprilysin Inhibitors (ARNi)?
Affect both the NP system and the RAAS system
-blocks the angiotensin receptor
-inhibits BNP degradation
*dual action makes drug more beneficial
What is the only ARNi currently available?
Sacubitril/Valsartan
(Entresto)
What are the available doses of Entresto?
S 24mg, V 26mg
S 49mg, V 51mg
S 97mg, V 103mg
What are the adverse effects of Entresto (Sacubitril/Valsartan)?
-Hypotension
-Elevated SeCr, k
-Angioedema
-Pregnancy contraindicated
What is the cost of Entresto?
about $600/month
What was the trial that tested ARNi vs ACEi?
Paradigm-HF trial
(think that the goal of the trial was to create a paradigm shift in HF treatment)
What are the 3 specific criteria that patients had to meet in the Paradigm-HF trial for use of ARNi?
SBP >100
K <5.2
eGFR >30
For patients currently taking a high-dose ACEi or ARB, what are the starting and max doses of Entresto they can receive?
Start: S 49/V 51 mg BID
Max: S 97/ V 103 mg BID
*High dose ACEi= >10 mg/day enalapril or equivalent
*High dose ARB= > 160 mg/ day valsartan or equivalent
What is considered a high-dose ACEi?
> 10 mg/day enalapril or equivalent
What is considered a high-dose ARB?
> 160 mg/day valsartan or equivalent
What Entresto dose should patients on a low-medium ACEi/ARB dose or who are ACEi/ARB naive receive?
24/26 mg BID
Besides low-medium dose ACEi/ARB patients, who else should receive an initial Entresto dose of 24/26 mg BID?
eGFR < 30
Moderate hepatic impairment
Age > 75
How soon before starting an ARNi should an ACEi be stopped?
36 hours
What are the contraindications for ARNi’s?
Angioedema with an ACEi or ARB
Pregnancy
Lactation
*Starting within 36 hours of being on an ACEi
What RAAS inhibitor should be used as first-line treatment in Stage B patients?
ACEi
(then ARB if intolerant)
What RAAS inhibitor should be used as first-line treatment in Stage C patients?
ARNi preferred!!!!
-Then ACEi, then ARB
True or False: Replacing an ACEi or ARB with an ARNi further reduces mortality
TRUE
What Stages of heart failure should ARNi’s be used in?
Stage C
**not B!!!
What are the 3 beta blockers we use in HF treatment?
Carvedilol
Metoprolol Succinate (XL)
Bisoprolol
One is a proposed benefit of beta blocker usage?
Able to reverse remodeling
What is the MOA of beta blockers in HF?
Increased norepinephrine in the heart has many detrimental effects:
-Beta-adrenergic receptor pathway desensitization leads to impaired exercise tolerance
-Myocyte toxicity leads to myocardial dysfunction
*These both lead to HF
*Want to block the effects of increased cardiac NE with beta blockers
What neurotransmitters are blocked by beta blockers?
Norepinephrine
Epinephrine
Angiotensin II
*all blocked from reaching the myocyte and stimulating beta and AT receptors
By blocking neurotransmitters, what are beta blockers decreasing?
-Arrythmias
-Cardiac hypertrophy and cell death
-Vasoconstriction
-Heart Rate
-Cardiac remodeling
What patients should not receive beta blockers or have them titrated if already on?
Unstable HF patients
Patients who are not euvolemic
*Cautiously consider in patients with bronchospastic disease and asymptomatic bradycardia
*CAN administer to hospitalized patients, but do so later in their stay
Why should beta blockers not be discontinued abruptly?
Rebound hypertension
(because of upregulation in beta receptors while on a beta blocker that can now all be activated)
What is the initial and target dose of bisoprolol (Zebeta)?
Init: 1.25 mg daily
Target: 10 mg daily
What is the initial and target dose of Carvedilol (Both Coreg and Coreg CR)?
Coreg:
Init: 3.125 mg BID
Targ: 25-50 mg BID
Coreg CR:
Init: 10 mg daily
Targ: 80 mg daily
What is the initial and target dose of Metoprolol CR/XL (succinate)?
Init: 12.5-25 mg daily
Targ: 200 mg daily
How do we titrate beta blockers?
Double the dose ever 2 weeks
Aim for target dose in 8-12 weeks
Monitor for symptomatic hypotension and HR
Monitor for edema, fluid retention, fatigue, and weakness
What is the goal heart rate of beta blockers in HF?
NO GOAL
-just want to get to therapeutic dose
-do not push HR below 50 bpm
-avoid symptomatic brdycardia
What stage of heart failure patients should receive beta blockers?
BOTH B and C!
*all patients
What does elevated aldosterone in HF lead to?
-Continued sympathetic activation
-Parasympathetic inhibition
-Cardiac and vascular remodeling
What are the two Aldosterone Receptor Antagonists (MRA)?
Spironolactone (nonselective)
Eplerenone (selective)
What affect do MRA’s have on electrolytes?
Decrease K and Mg losses (increase these)
(protects against arrythmias)
Decrease Na retention
(decreases fluid retention)
What are the adverse effects of spironolactone?
Gynecomastia
Impotence
Menstrual Irregularities
What is the initial and maintenance dosing of eplerenone?
CrCl > = 50:
Init: 25 mg QD
Maint: 50 mg QD
CrCl 30-49:
Init: 25 mg every other day
Maint: 25 mg QD
What is the initial and maintenance dosing of spironolactone?
CrCl > = 50:
Init: 12.5-25 mg QD
Maint: 25 mg QD
CrCl 30-49:
Init: 12.5 mg QD or every other day
Maint: 12.5-25 mg QD
When should MRA’s be avoided?
SeCr > 2.5 mg/dL (men) or >2 mg/dL (women)
CrCl < 30 mL/min
K > 5 mEq/L *
History of severe hyperkalemia
Recent worsening renal symptoms
What drug class should be avoided with MRA’s?
NSAIDs
What should be monitored with MRA’s?
Renal function and K: within 3 days-1 week after a change, then every month for 3 months, then every 3-4 months and with ACEi or ARB change
What Stage heart failure patients should receive MRA’s?
NOT STAGE B
Stage C: Patients with class II-IV and HFrEF
At what K level should MRA’s be DISCONTINUED?
5.5
*if it cannot be maintained be low this level, discontinue
What are the mechanisms by which SGLT2i work?
-Reduce preload
-Reduce afterload
-Cause diuresis
Possible ways they reduce mortality:
-Myocardial energetics and metabolomics (effect mitochondrial use of oxygen)
-Direct effects on myocardium
**Reduced myocardial remodeling
What are the 2 SGLT2i used in HF and how are they dosed?
Dapagliflozin (Farxiga): 10 mg QD
Empagliflozin (Jardiance): 10 mg QD
What levels of renal function are required to use the two SGLT2i?
Dapa: eGFR >= 30
Empa: eGFR >= 20
What are the adverse effects associated with SGLT2i?
-Volume depletion
-Ketoacidosis
-Hypoglycemia
-Infection risk (UTI* empagliflozin*)
Who should receive SGLT2i?
ALL HFrEF patients with symptoms
What are the effects of ISDN/Hydralazine?
Reduces both preload and afterload
(balanced vasodilatory effects)
*First drug combo to reduce mortality
When do we use ISDN/Hydralazine (BiDil)?
ADJUNCT to standard treatment of HF in black patients
What is a problem associated with ISDN/Hydralazine (BiDil) use?
Many adverse effects!
-Headache, nausea, flushing, dizziness, tachycardia, hypotension, high HR, myocardial ischemia, fluid retention
**Lupus-like syndrome
*does not help that we have to use it at high doses
What are the initial and target doses of ISDN/Hydralazine (BiDil)?
Init: I 20/ H 37.5 mg TID
Target: I 40/ H 75 mg TID
What class of HF patients should receive ISDN/Hydralazine (BiDil)?
NOT STAGE B
Stage C:
-black patients who are class 3-4, receiving optimal therapy, and continue to have symptoms
-patients who cannot receive ARNI, ACEi, or ARB
When would we use Ivabradine (Corlanor)?
To reduce the risk of hospitalizations in patients with:
EF <= 35%
HR >= 70 *on max beta blocker
What is the dosing of Ivabradine (Corlanor)?
Initial: 2.5-5 mg BID
Adjust every 2 weeks based on HR:
>60: Increase by 2.5 up to 7.5 mg BID
50-60: Maintain dose
<50: Decrease dose by 2.5 mg BID
What are the adverse effects of Ivabradine?
-Fetal toxicity
-Afib
-Bradycardia and conduction disturbances
*cost is a major downside of this drug (>$6000/year)
what drugs should be avoided with Ivabradine?
Ketoconazole
Diltiazem + Verapamil
*Grape Fruit Juice
*Drug is a CYP3A4 substrate
What is the MOA of Digoxin?
Blocks the Na/K ATPase
*this leads to an increase of intracellular Ca concentrations which INCREASES CONTRACTILITY
*positive inotrope
Stimulates the PSNS which counteracts the SNS to REDUCE HR
(neurohormonal modulation effects)
When do we use Digoxin?
In patients with symptoms despite optimized therapy or who cannot tolerate the guideline directed therapy
*Decreases hospitalizations in these patients but not mortality
What is the typical dosing of Digoxin?
0.125-0.25 mg QD
*Note: narrow therapeutic index drug, have to be careful dosing
What is the goal serum digoxin concentration?
0.5-0.9 ng/mL
Who should receive lower doses of Digoxin?
> 70 yrs old
Impaired renal function
Low weight
What drugs interact with Digoxin?
-Amiodarone
-Quinidine
-Verapamil***
*Itraconazole/Ketoconazole
*Need to decrease digoxin dosing when these are started!
What are the adverse effects associated with Digoxin?
Anorexia, nausea, vomiting, abdominal pain
*Visual disturbances
Fatigue, weakness, dizziness, headache, neuralgias, confusion, delirium, psychosis
Many cardiac symptoms
When should we use Vericiguat?
To reduce CV death and hospitalization
*Consider in select high-risk patients with recent worsening symptoms despite optimized therapy
When is aspirin recommended in HF?
For patients with HF and IHD/CAD/ASCVD
*otherwise not indicated
*use 75-81 mg/day
If we need to manage angina/HTN, what CCBs can be used?
Felodipine or Amlodipine
*DO NOT USE diltiazem, verapamil, or nifedipine
What drug classes should all HFpEF patients be put on?
SGLT2i
-decrease mortality
**no other drugs decrease mortality and should be considered on case-to-case basis to reduce hospitalizations
True or False: We do not use Digoxin in HFpEF
TRUE
-no affect on mortality or hospitalizations
