Sowinski Heart Failure Part 3 Flashcards
What does elevated aldosterone lead to in HF?
-Continued sympathetic activation
-Parasympathetic inhibition
-Cardiac and vascular remodeling
Beneficial effects of aldosterone receptor antagonists
-Decrease K and Mg losses: May protect against arrhythmias
-Decrease Na retention: Decrease fluid retention
-Decreases sympathetic stimulation: numerous effects
-Blocks direct fibrotic action on myocardium
Spironolactone mechanism of action
-Non-selective agent, structurally similar to progesterone
-Inhibits the effects of dihydrotestosterone at the receptor site and increases peripheral conversion of testosterone into estradiol
Spironolactone adverse effects
-Gynecomastia
-Impotence
-Menstrual irregularities
Eplerenone mechanism of action
-Selective agent with 100- to 1000-fold lower affinity for androgen, glucocorticoid, and progesterone receptors than spironolactone
-No antiandrogenic effects
-Substrate of CYP3A4
Initial dosing for eplerenone when eCrCl is 50 or more
25 mg once daily
Initial dosing for eplerenone when eCrCl is 30-49
25 mg every other day
Initial dosing for spironolactone when eCrCl is 50 or more
12.5-25 mg once daily
Initial dosing for spironolactone when eCrCl is 30-49
12.5 mg every other day
Maintenance dosing for eplerenone when eCrCl is 50 or more
50 mg once daily
Maintenance dosing for eplerenone when eCrCl is 30-49
25 mg once daily
Maintenance dosing for spironolactone when eCrCl is 50 or more
25 mg once daily
Maintenance dosing for spironolactone when eCrCl is 30-49
12.5-25 mg once daily
When should aldosterone antagonists be avoided?
-SeCr >2.5 for men and >2.0 for women (or CrCl <30)
-SeK >5
-History of severe hyperkalemia or recent worsening renal function
What should be avoided when taking aldosterone antagonists?
-Concomitant use of potassium sparing diuretics or potassium supplements (unless hypokalemic with SeK <4)
-NSAIDS
-Caution when using with high dose ARNI/ARB
Aldosterone antagonist monitoring
-Renal function and potassium within 3 days-1 week after change or addition
-Diseases or acute illnesses that may influence potassium concentrations
-Monitor every month for 3 months then every 3-4 months
-Monitor with increased ACEI or ARB restart
What should patients taking aldosterone antagonists be counseled on?
-Avoidance of salt substitutes
-Close questioning for all other sources of potassium
Stage B recommendations for aldosterone antagonist use
Not recommended
Stage C recommendations for aldosterone antagonist use
-Should be used in all patients with NYHA II-IV and HFrEF, and eGFR >30 and K <5
-Careful monitoring of K, renal function, and diuretic dosing is essential
-Patients taking aldosterone antagonists in which potassium can not be maintained below 5.5 should be discontinued to avoid life threatening hyperkalemia
SGLT2 inhibitors benefits in HFrEF patients
-Unclear benefits in heart failure
-Osmotic diuresis and natriuresis
-Decreased arterial pressure and stiffness
-Preload and afterload reduction and associated reduction in hypertrophy and fibrosis
-Reduced myocardial remodeling
SGLT2I indication
Reduce the risk of CV death or hospitalization for HFrEF patients with NYHA class II-IV
Dapagliflozin dosing
10 mg once daily
Empagliflozin dosing
10 mg once daily
At what eGFR can dapagliflozin be used?
30 or more
At what eGFR can empagliflozin be used?
20 or more
Adverse effects of SGLT2 inhibitors
-Volume depletion
-KTA in DM
-Hypoglycemia
-Infection risk (UTI/PN, NFP, Mycotic)
When are SGLT2 inhibitors recommended?
Patients with symptomatic chronic HFrEF with or without DM to reduce hospitalizations and CV mortality
ISDN/Hydralazine mechanism of action
Combination produces VD effects, causing reductions in both preload and afterload
When is ISDN/Hydralazine indicated?
For the treatment of HF in black patients as an adjunct to standard therapy
Adverse effects of ISDN/Hydralazine
-Headache
-Nausea
-Flushing
-Dizziness
-Tachycardia
-Lupus-like syndrome
-Hypotension
-Increased heart rate
-Myocardial ischemia
-Fluid retention
-AEs are a significant problem and a major limiting factor in clinical trials
Initial hydralazine dose
25 mg TID/QD
Target hydralazine dose
75 mg TID
Maximal hydralazine dose
100 mg TID
Initial ISDN dose
20 mg TID/QD
Target ISDN dose
40 mg TID
Maximal ISDN dose
80 mg TID
Initial ISDN/Hydralazine dose
20/37.5 mg TID
Target/maximal ISDN/Hydralazine dose
40/75 mg TID
Stage B recommendations for ISDN/Hydralazine
No recommendations
Stage C recommendations for ISDN/Hydralazine
-Black patients with NYHA III-IV, receiving optimal medical therapy, to improve symptoms and reduce M/M
-Patients with symptoms, who can not receive ARNI, ACE or ARB might be considered
Ivabradine indication
Reduce the risk of hospitalization for symptomatic HF, EF <35% in NSR with rHR 70 or more in max tolerated beta-blocker or with CI
Maintenance dosing for ivabradine
-2.5-5 mg BID
-Adjust every 2 weeks based on HR
Max dose for ivabradine
7.5 mg BID
How should ivabradine be adjusted when HR is greater than 60?
Increase dose by 2.5 mg (given BID) up to a maximum dose of 7.5 mg BID
How should ivabradine be adjusted when HR is 50-60?
Maintain dose
How should ivabradine be adjusted if HR is less than 50 or signs/symptoms of bradycardia?
Decrease dose by 2.5 mg (given BID); if current dose is 2.5 mg BID, discontinue therapy
Adverse effects of ivabradine
-Fetal toxicity
-Atrial fibrillation
-Bradycardia and conduction disturbances
-Cost: >$6000/year
Ivabradine contraindications
-KTZ CI
-Avoid diltiazem, verapamil, GFJ
Digoxin benefits
-Benefits are due to neurohormonal modulation effects
-Increases parasympathetic activity
-Vagolytic effects at the AV and SA nods]es . . . reduces HR at rest and slows AVN conduction
-Re-sensitization of baroreceptors
-Inhibits the Na+/K+ ATPase altering excitation- contraction-coupling
-Increases intracellular Ca2+, enhancing the force of contraction
-Relatively mild positive inotrope
When to consider digoxin for treatment of HF
Consider in patients with symptomatic HFrEF despite (optimized) GDMT, or who can not tolerate GDMT to decrease hospitalization for HF
Digoxin dosing
-Most of the time digoxin is dosed empirically
-0.125-0.25 mg daily
-0.125 mg used in the majority of patients with 0.5-0.9 ng/mL being the goal serum digoxin concentration
-Lower doses in >70 years, impaired renal function, low weight
Digoxin drug interactions
-Amiodarone (doubles concentration)
-Quinidine
-Verapamil
-Itra/KTZ
Noncardiac adverse effects of digoxin
-Anorexia, nausea, vomiting, abdominal pain
-Visual disturbances: halos, photophobia, altered color perception
-Fatigue, weakness, dizziness, headache, neuralgias, confusion, delirium, psychosis
Cardiac adverse effects of digoxin
-Ventricular: PVCs, bigeminy, trigeminy, VT, VF
-AV block: First, second and third degree
-AV junctional escape rhythms, junctional tachycardia
-Atrial arrhythmias with slowed AV conduction or AV block
-Sinus bradycardia
Vericiguat mechanism of action
Soluble guanylate cyclase stimulator
Vericiguat contraindication
Pregnancy
Vericiguat adverse effects
-Hypotension
-Anemia
When to consider vericiguat in HF treatment
Consider in selected high-risk patients with recent worsening with symptomatic HFrEF despite (optimized) GDMT, to decrease hospitalization for HF and CV death
When are omega-3 polyunsaturated fatty acids recommended in the treatment of HF?
Reasonable as adjunctive therapy
When are antiplatelets recommended in the treatment of HF?
-Long term therapy with aspirin (75-81 mg/day) is recommended in patients with HF and IHD/CAD/ASCVD
-Otherwise aspirin is not recommended for routine use
-If contraindicated/not tolerated, consider alternatives
When are anticoagulants recommended in the treatment of HF?
-Recommended in HF if atrial fib with one additional risk factor
-Reasonable if no additional risk factors
-Patients with other indications such as history of systemic or pulmonary embolism
-Routine anticoagulation is not recommended
When are calcium channel antagonists recommended in the treatment of HF?
-Diltiazem, verapamil and nifedipine should not be routinely used
-Felodipine and amlodipine may be useful in managing angina/HTN if not effectively managed with HF therapies
Non-pharmacologic therapies for HF
-Implantation of ICD
-Cardiac resynchronization therapy
Treatment of HFpEF
-SBP/DBP should be controlled in patients with HFpEF based on current practice
-Diuretics should be used for relief of symptoms due to volume overload in patients with HFpEF, no mortality benefits
-Management of AF according to published clinical practice guidelines in patients with HFpEF can improve symptomatic HF
-SGLT2i may reduce hospitalizations and CV mortality
-The use of ARBs, ARNIs, MRAs, and ACEIs may be considered to decrease hospitalizations for selected patients with HFpEF, especially at the lower end of LVEF
-ACEIs and ARBS have not been shown to reduce mortality (ACEIs improve exercise tolerance and reduce hospitalizations) (ARBs may reduce hospitalizations)
-MRAs may improve diastolic function and reduce remodeling (less convincing than HFrEF)
-Digoxin has no affect on mortality or hospitalizations
-Nitrates should be limited to use in patients with HFpEF who may need treatment for symptomatic CAD
-CCBs may be useful to treat other conditions such as HTN
