CHF

Question 1

causes of HF

Answer 1

-usually a consequence of underlying CV disorders
-Myocardial infarction – MC cause of systolic dysfunction
-Other cardiovascular causes
-non cardiac causes:
-1. Severe anemia
-2. Nutritional Deficiencies- K and Ca
-3. Drugs:
-chemotherapy agents (i.e. doxorubicin)
-COX-2 inhibitors
-NSAIDs
-thiazolidinediones (“glitazones”)- DM

Question 2

systolic dysfunction

Answer 2

-decrease contractility
-Reduction in muscle mass (MI)
-Dilated cardiomyopathies
-Ventricular Hypertrophy – pressure overload (systemic and pulmonary HTN, aortic or pulmonic valve stenosis)
-Ventricular Hypertrophy – volume overload (valvular regurgitation, shunts, high-output states)

Question 3

diastolic dysfunction

Answer 3

-restriction in ventricular stiffness
-increased ventricular stiffness
-ventricular hypertrophy
-infiltrative myocardial disease (amyloidosis, sarcoidosis)
-myocardial ischemia and infarction
-mitral and tricuspid valve stenosis
-pericardial disease

Question 4

pathophysiology of HF

Answer 4

-Reduction in stroke volume and CO by measurement of ventricular end-diastolic pressure (preload)
-1. Reduced stroke volume caused by either diastolic or systolic dysfunction

-Left-sided failure:
-LV doesn’t adequately pump blood forward -> increase pulmonary circulation pressure -> fluid forced into lung insterstitium -> congestion and edema -> reduction of diffusion of O2 and CO2 between alveoli and pulmonary capillaries -> hypoxemia (decrease oxygenation in blood) -> tissue hypoxia and organ dysfunction OR dyspnea (exertional, orthopnea, paroxysmal nocturnal)

-right HF- congestion in peripheral veins -> hepatojugular reflex (increase in jugular vein distension when pressure applied over the liver) OR ankle edema (ambulatory pt and sacral edema (bedridden pt))

-compensatory neurohormonal responses- triggered in response to reduction in CO
-reduction in tissue perfusion -> activation of SNS, RAAS, vasopressin, proinflammatory cytokines -> increase vasoconstriction, increase tachycardia, increase Na and H2O retention, increase preload, and SV, ventricular hypertrophy and remodeling -> increase plasma volume and venous pressure OR decrease CO and increase circulatory congestion

Question 5

risk factors to HF

Answer 5

-risk factors- hyperlipidemia, HTN, diabetes, insulin resistance ->
-atherosclerosis LVH ->
-CAD ->
-Myocardial ischemia ->
-coronary thrombosis ->
-MI -> arrhythmia and loss of muscle
-arrhythmia -> sudden death
-loss of muscle -> remodeling -> ventricular dilation -> HF -> death

Question 6

staging of HF: American College of Cardiology/American Heart Association (ACCF/AHA)

Answer 6

-Stage A – At risk for HF w/o structural heart disease or signs & symptoms of HF
-Stage B – Structural heart disease w/o signs & symptoms of HF
-Stage C – Structural heart disease with prior or current symptoms of HF
-Stage D – Refractory HF requiring specialized interventions

Question 7

staging of HF: heart failure society of america (HFSA)

Answer 7

-CLASS I – No limitations of physical activity. Ordinary Physical Activity does not cause undue fatigue, dyspnea or palpitations
-CLASS II – Slight limitations of physical activity. Ordinary physical activity results in fatigue, palpitation, dyspnea or angina
-CLASS III – Marked limitation of physical activity. Although patients are comfortable at rest, less-than-ordinary physical activity will lead to symptoms
-CLASS IV – Symptomatic at rest. Symptoms of CHF are present at rest and the discomfort increases with any physical activity

Question 8

stages, phenotypes and treatment of HF

Answer 8

Question 9

treatment of HF stage C and D

Answer 9

Question 10

classes of drugs used to treat HF: diuretics

Answer 10

-MOA- reduce plasma volume and edema -> relieve symptoms of circulatory congestion
-Thiazide diuretics (HCTZ) – for milder cases
-Loop diuretics (IV/PO)
-aldosterone antagonists (spironolactone)

Question 11

loop diuretics

Answer 11

-IV/PO
-more potent natriuretic activity
-Carefully titrate doses to avoid excessive diuresis, dehydration and electrolyte imbalances
-Examples:
-Furosemide (Lasix)
-Torsemide (Demadex)
-Bumetanide (Bumex)

Question 12

general side effects for loops and thiazides

Answer 12

-hypokalemia
-hypomagnesaemia
-hypocalcemia (loops)
-tachycardia
-Important ions to maintain normal cardiac function are Ca2+, Mg+and K+
-Common to give K+ supps and Mg+ supps in CHF patients
-Refer to HTN handout for full list of ADRs

Question 13

diuretics: aldosterone antagonists

Answer 13

-spironolactone
-reserve for pts with symptoms at rest despite the use of diuretics, digoxin, ACE inhibitors and beta-blockers
-Use low dose and closely monitor potassium.
-HFSA guidelines: Use IV loop diuretics as initial tx for pts w/ ADHF and evidence of fluid overload
-ACC/AHA guidelines:
-Use PO diuretics to maximize standard HF therapies (ACE inhibitors, BBs) in patients w/ Stage C Heart Failure
-Use aldosterone antagonist in selected Stage C HF pts w/ moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal fn and normal K+ concentration

Question 14

vasodilators

Answer 14

-ACE inhibitors- prils
-ARB- sartan- used in pts intolerant to ACE inhibitors
-ARNI- angiotensin receptor neprolysin inhibitor (combination)
-isosorbide dinitrate (ISDN)
-hydralazine (HYD)
-hydralazine/isosorbide combo (BIDIL)
-HCN channel blocker

Question 15

ACE inhibitors

Answer 15

-prils
-reduce formation of Angiotensin II, therefore counteract the activation of the renin-angiotensin aldosterone system, which occurs during compensatory mechanism of heart failure
-results in venous and arterial dilation, reduction in plasma volume, venous pressure and edema as well as increase in CO by reducing arterial pressure and cardiac afterload.
-Several studies demonstrate reduced mortality in pts with heart failure
-SEs - nonproductive cough (20%), rash, abnl taste, hyperkalemia, dizziness, decrease renal function, angioedema.
-ACC/AHA guidelines: ACE inhibitors/ARBs should be used in appropriate patients starting at Stage A HF (i.e. HTN, MI)

Question 16

angiotensin receptor blockers

Answer 16

-sartan
-used in pts intolerant to ACE inhibitors

Question 17

ARNI- angiotensin receptor neprolysin inhibitor (combination)

Answer 17

-Valsartan / Sacubitril
-MOA - Angiotensin Receptor Neprolysin Inhibitor – Valsartan decreases RAAS (dec Na & H20 retention, dec vasoconstriction, dec fibrosis) Sacubitril increases natiuretic peptide system (inc natiuresis, inc diuresis, inc vasodilation, inhibit fibrosis)
-Dec in morbidity & mortallity
-decrease fibrosis!
-SEs – hypotension, hyperkalemia, cough, dizziness, acute renal failure

Question 18

isosorbide dinitrate (ISDN)

Answer 18

-Relaxes venous smooth muscle more than arterial smooth muscle therefore reduces venous volume and pressure and reduces pulmonary congestions
-Often combined w/ hydralazine (arterial vasodilator) in pts who can not tolerate ACE inhibitors

Question 19

hydralazine (HYD)

Answer 19

-Relaxes arterial smooth muscle therefore reduces afterload and increase cardiac output.

Question 19

hydralazine/isosorbide combo (BIDIL)

Answer 19

-Newly approved drug to treat heart failure in African American patients
-First drug to be approved to treat a specific ethnic group

Question 20

HCN channel blocker

Answer 20

-Ivabradine (Corlanor)
-Mixed sodium and potassium channel that carries the If current
-REDUCE RATE
-Indication: indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use!!!!!!!!!!!!!!!!!1
-ADR: bradycardia, HTN, atrial fibrillation, and luminous phenomena (phosphenes) or visual brightness.
-Contraindications: patients with acute decompensated heart failure, blood pressure < 90/50 mmHg, sick sinus syndrome, sinoatrial block, 3rd degree atrioventricular block (unless a functioning demand pacemaker is present), a resting heart rate < 60 bpm prior to treatment, severe hepatic impairment, pacemaker dependence (heart rate maintained exclusively by the pacemaker), and concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors

Question 21

ACC/AHA guidelines for hydralazine/ISDN

Answer 21

-HYD/ISDN is recommended to improve outcomes for Stage C HF pts with moderate-severe symptoms and/or LVEF on optimal therapy w/ ACEIs, BBs and diuretics
-HYD/ISDN is reasonable in Stage C HF pts w/ current of prior symptoms of HF and reduced LVEF who can not tolerate ACEIs or ARBs.
-Class I - The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III–IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated
-Class IIa - A combination of hydralazine and isosorbide dini- trate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated

Question 22

beta blockers

Answer 22

-reduce excessive sympathetic stimulation of the heart and circulation in patients with heart failure
-SNS stimulation causes tachycardia, increase O2 demand, and increase stimulation of renin-angiotensin-aldosterone system
-Beta blockers can counteract all these effects.
-Cardioselective agents preferred (Metoprolol, Bisoprolol)
-Carvedilol (Coreg)
-ADRs for all beta blockers– bradycardia, dizziness, hypotension
-Studies have shown they reduce mortality associated w/ CHF
-ACC/AHA guidelines: BBs should be used in appropriate patients starting at Stage A or B Heart Failure (i.e. HTN, MI)

Question 23

carvedilol

Answer 23

-coreg
-Preferred beta-blocker for CHF
-Combo alpha1 and beta blocker
-Vasodilative
-Antioxidant properties

Question 24

digoxin

Answer 24

-PO, IV -Derived from leaves of digitalis (foxglove) plants and skin secretions of certain toads -Kinetics – long half life (35 hours) -> Renal elimination -Low therapeutic index. -Must monitor levels (nl range = 0.5-2 ng/mL)!!!!!!!!!* -positive inotrope - increase force of contraction by increase intracellular calcium and inhibiting sodium pump (increase intracellular Na+, increase Ca2+ entry, increase contraction). This in turn increase SV and CO. -negative chronotrope (decrease HR) -negative dromotrope (decrease in conduction velocity) -Direct effects on cardiac electrophysiology – afterdepolarizations may occur due to excessive Ca2+ influx leading to tachycardia, usually after higher doses. On ECG – shortens action potential duration, increase PR interval and decrease QT interval. -Indications – CHF, Atrial Fibrillation, Atrial Flutter, and supraventricular tachycardia and cardiogenic shock. NOT used for ventricular arrhythmia -Dosing – Need to give loading dose or digitilizing dose to get pt to steady state levels. IV doses are 20-25% less than PO dose. Reduce dose by 50% in pts with CrCl < 50 ml/min. Usual PO maintenance dose in adults is 0.125 – 0.25 mg/day -Digoxin can be beneficial in Stage C HF pts with current or prior symptoms and reduced LVEF to decrease hospitalizations.” -Digitoxin – not used as often, metabolized in liver, excreted in feces. Side effects same as digoxin

Question 25

digoxin side effects

Answer 25

1. GI effects 2. Confusion & Visual disturbances 3. Cardiac Toxicity -ADRs – Narrow therapeutic index -GI effects: anorexia, nausea and vomiting -Neurologic: confusion, weakness, fatigue, dizziness, headaches, mental disturbances and visual disturbances (blurred or yellow vision). -Cardiac: bradycardia, arrhythmias and AV block – increased risk w/ hypokalemia, hypomagnesaemia and hypercalcemia) -Other: Seizures – rarely. -DDI – CYP3A4 and P-gylcoprotein substrate; beta-blockers, amiodarone, cyclosporine can all increase digoxin effects. Diltiazem, quinidine and verapamil reducedigoxin clearance and increase digoxin levels. Caution w/ diuretics b/c of their effects on electrolytes. Antacids and cholestyramine can decrease digoxin effects.

Question 26

digoxin antidote

Answer 26

-Digibind (digoxin immune binding fragments are specific antibodies – bind w/ molecules of digoxin and excreted renally -Used in cases of severe toxicity -Treat symptomatically (i.e. treat hypokalemia with K+ and arrhythmias with lidocaine)

Question 27

IV inotropes for acute decompensated HF (ADHF)

Answer 27

-adrenergic agonists- dobutamine (IV) -phosphodiesterase (PDE) inhibitors- amrinone and milrinone (IV) -***Heart Failure Society of America (HFSA) Guidelines state: “IV inotropes may be considered in pts with advance HF and low output syndrome to relieve symptoms and improve end organ function. Their use should be severely limited”

Question 27

IV INOTROPES FOR ACUTE DECOMPENSATED HEART FAILURE (ADHF): adrenergic agonists: dobutamine

Answer 27

-Dobutamine (IV infusion) -limited to short term management of ADHF -Selective beta agonists – selectively stimulate cardiac contractility -mild vasodilative effect

Question 27

IV INOTROPES FOR ACUTE DECOMPENSATED HEART FAILURE (ADHF): phosphodiesterase (PDE) inhibitors

Answer 27

-amrinone and *milrinone (IV)* -inhibit type III PDE -> increase cAMP concentration in cardiac tissue and vascular smooth muscle -> increase cardiac contractility and relaxes vascular smooth muscle -Reserved for short-term management of ADHF or for acute exacerbations of chronic heart failure in pts who do not respond to other drugs. -Long-term use may cause thrombocytopenia and ventricular arrhythmias -increase mortality- not reduce

Question 28

IV vasodilators for acute decompensated HF

Answer 28

-nesiritide IV -nitroprussuide IV -nitroglycerin IV -*** Heart Failure Society of America Guidelines state : “IV vasodilators may be considered in addition to diuretics for rapid improvement in congestive symptoms in pts w/ ADHF in the absence of SYMPTOMATIC hypotension”

Question 29

IV VASODILATORS for ACUTE DECOMPENSATED HEART FAILURE: nesiritide IV

Answer 29

-Vasodilator -B-type human natriuretic peptide. Binds to guanylate cyclase receptor on vascular smooth muscle -> increase cyclic GMP -> smooth muscle relaxation -Indications – Tx of acutely decompensated CHF in pts with dyspnea at rest or with minimal activity. -Contraindicated in cardiogenic shock or hypotension (SBP < 90) -SEs – hypotension, increase Cr, headache, dizziness, N,V,D -Dosing – specific dosing and administration guidelines

Question 30

IV VASODILATORS for ACUTE DECOMPENSATED HEART FAILURE: nitroprusside IV

Answer 30

-arterial and venous vasodilator. increase Nitric oxide synthesis. -Indications – Treatment of acutely decompensated congestive heart failure and Hypertensive Crisis -Caution – Cyanide Toxicity

Question 31

IV VASODILATORS for ACUTE DECOMPENSATED HEART FAILURE: nitroglycerin IV

Answer 31

-MOA – Venous vasodilator > arterial vasodilator. increase cyclic GMP -Indications – Tx of acutely decompensated congestive heart failure, Hypertensive Crisis and Acute Coronary Syndromes -Comments: Tolerance can occur. Shortest half-life of three IV VDs for Acute Decompensate Heart Failure

Question 32

investigational tx

Answer 32

1. Vasopeptide inhibitors 2. Cytokine antagonists 3. Endothelin antagonists

Question 33

overall management of HF

Answer 33

-Often 3 drug combination with beta blocker, ace inhibitor and diuretic (BAD) -Other drugs used if patient intolerant to or inadequate response to above drugs. Also, other drugs used for acute heart failure or exacerbations of chronic heart failure

Question 34

summary

Answer 34

-Pathophysiology of Heart Failure involves reduction in SV and CO. Heart failure can be either left-sided or right-sided. Compensatory mechanisms will exacerbate and worsen existing heart failure. -Drug treatment is based on clinical symptoms and staging. There are 2 main staging classifications for heart failure (NYHA or ACC/AHA Criteria) -3 main classes of drugs are used to treat heart failure – BAD -Loop diuretics are most effective for reducing the symptoms associated with CHF exacerbations (fluid overload, edema) -ACE inhibitors – effective vasodilators – reduce preload AND afterload. Reduce mortality. Start therapy at Stage A Heart Failure. -Beta Blockers – reduces excessive SNS stimulation. Use with caution in late stage or decompensated heart failure b/c they reduce contractility. Carvediliol is preferred agent b/c it also blocks alpha 1 receptor. Reduce mortality. Start Therapy at Stage A or B Heart Failure -Digoxin is a positive inotrope – especially useful if added in Stage C Heart Failure to improve symptoms and reduce hospitalizations. Narrow therapeutic index, monitor for digoxin toxicity. -HYD/ISDN and Aldosterone Antagonists can be used as in selected Stage C Heart Failure patients usually who are having symptoms despite optimal therapy w/ ACEIs, BBs and diuretics