The Treatment Of Heart Failure

Front 1

The Frank-Starling mechanism, which maintains ___________ in the face of an increase in _____________, no longer works in a patient with heart failure caused by systolic dysfunction.

Back 1

1. stroke volume
2. afterload (DBP)

Front 2

In patients w/ heart failure, as the heart failure gets worse the rate of decline of SV for every unit change in DBP (increases/decreases). Also, stroke volume (increases/decreases) as DBP increases.

Back 2

1. Increases
2. Decreases

Front 3

What is the effect of increased preload, contractility, and afterload on stroke volume in a normal heart? In a failing heart?

Back 3

Normal: Increase, Increase, No change

Failing: Decrease, Increase, Decrease

Front 4

Decreased ability to exercise, fatigue, tachycardia, hypotension are symptoms of (forward/backward) failure while pulmonary edema, dyspnea, right heart failure, and peripheral edema are symptoms of (forward/backward) failure

Back 4

1. Forward
2. Backward

Front 5

What drugs classes in general will allow the failing heart to operate on a "new" Starling curve?

Back 5

1. Balanced vasodilators
2. + Inotropic agents

Front 6

What drug class can decrease backward failure but not have an affect on improving forward failure?

Back 6

Diuretics

Front 7

What are four strategies aimed at improving symptoms of heart failure?

Back 7

1. Decrease preload (diuretics/nitrate vasodilators)
2. Decrease afterload (arteriolar vasodilatior)
3. Decrease preload and afterload via "balanced" vasodilation of arterioles and venules (ACE inhibitor or ARB)
4. Increase contractility via a direct + inotropic action

Front 8

Strategies aimed at reversing cardiac remodeling and increasing longevity include:

Back 8

1. Blocking cardiac AngII receptors
2. Blocking cardiac Aldo receptors
3. Blocking cardiac Adrenergic receptors (B1, B2, alpha1)

Front 9

Drugs which decrease congestive symptoms, but do not increase SV, reverse cardiac remodeling, or increase longevity include:

Back 9

1. Furosemide
2. Isosorbide dinitrate

Front 10

What is the MOA of Furosemide in relieving congestive symptoms in heart failure?

Back 10

Saluresis decreases ECF volume --> preload & LV filling pressure are decreased

Decreased preload alleviates the congestive symptoms of "backward" failure

i.v. Furosemide also stimulates PG synthesis in the Kidney --> PG spills into systemic circulation --> increase in venous capacitance and a decrease in preload

Front 11

What is the dosing interval for the loop diuretics in heart failure?

Back 11

2-3 time per day bc of the short duration of action & the compensatory increase in salt & water reabsorption which occurs after each treatment

Front 12

What drug should you give with Furosemide to prevent hypokalemia?

Back 12

Spironolactone

Front 13

What drug given p.o. selectively dilates the venules and thus decreases cardiac preload?

Back 13

Isosorbide dinitrate

Front 14

What drugs increase EF and SV, decrease congestive symptoms, reverse cardiac remodeling & increase longevity? (the balanced vasodilators)

Back 14

1. Captopril, Enalapril, Lisinopril
2. Losartan, Valsartan
3. Isosorbide dinitrate + hydralazine

Front 15

What drugs are ACE inhibitors?

Back 15

Captopril
Enalapril
Lisinopril

Front 16

Should the dose of ACE inhibitor be larger or smaller than the dose used in the treatment of hypertension?

Back 16

LARGER

Front 17

What are the hemodynamic effects resulting from balanced vasodilation?

Back 17

1. Venodilation decreases preload, LV-EDV & LV-EDP & left atrial pressure decrease

2. Arteriolar dilation decreases afterload; results in an increase in EF & SV; increased SV also contributes to the decreases in LV-EDV, LV-EDP, and left atrial pressure

3. Increased SV & decreased LV-EDV/EDP decrease LV wall stress & pulmonary congestion

4. RBF & GFR are increased; RBF inc more than GFR --> FF decreases --> Diuresis

5. MAP & HR = no change or slight decrease

Front 18

ALL patients with HF should be treated with an ___________ because these drugs?

Back 18

ACE Inhibitor

1. prevent/reverse the cardiac remodeling by AngII

2. improve functional status & quality of life

3. decrease hospitalization & mortality

Front 19

What two things should be monitored in patients on ACE inhibitors, especially if renal function is poor?

Back 19

1. Plasma potassium
2. Serum creatinine

Front 20

Treatment with an ACE inhibitor after MI decreases the incidence of ____________ & __________.

Back 20

1. Systolic HF
2. Death

Front 21

What drugs cause hemodynamic changes that are almost the same as those caused by ACE inhibitors and can be substituted for ACE inhibitors?

Back 21

Angiotensin receptor blockers:
1. Losartan
2. Valsartan

Front 22

Other than ACE inhibitors and ARBs, what drug combination can be used to achieve balanced vasodilation?

Back 22

Isosorbide dinitrate + hydralazine
(venodilator) (arterial vasodil)

Front 23

What does prolonged treatment with Hydralazine frequently cause?

Back 23

SLE-like syndrome; especially in slow acetylators

Front 24

What drugs decrease backward failure, reverse cardiac remodeling, and increase longevity?

Back 24

Aldosterone receptor antagonists:

1. Spironolactone
2. Eplerenone

Front 25

What is the mechanism by which Aldosterone receptor antagonists reverses the cardiac remodeling caused by Aldosterone?

Back 25

Decreases the turnover of collagen in the ECM of the ventricles

Front 26

The incidence of _____________ increases as the dose of Spironolactone & Eplerenone are increased.

Back 26

Hyperkalemia

Front 27

Spironolactone & Eplerenone may cause marked hyperkalemia in patients with _____________ especially if the patient is also taking an ACE inhibitor other than ____________.

Back 27

1. poor renal function
2. Captopril

*Captopril has a half-life of only 2 h whereas the other ACEI's have half-lives of 12+ hours

Front 28

In patients with impaired renal function and HF, what is the the preferred ACE inhibitor?

Back 28

Captopril

*has a half life of 2 h and only prevents the formation of AngII for part of the day

* AngII maintains GFR by preferentially constricting the efferent arteriole

Front 29

Small doses of Spironolactone are effective in blocking Aldosterone receptors and usually do not pose a risk for hyperkalemia as long as serum Cr is below ________

Back 29

2.5 mg/dL

Front 30

True/False

Eplerenone is NOT a partial agonist at androgen, estrogen, and progesterone receptors, and thus does not cause gynecomastia, breast pain, azoospermia, or hirsuitism and menstrual irregularity

Back 30

True

Front 31

What drug is a beta-adrenoceptor antagonist that reverse/prevent cardiac remodeling caused by excessive sympathetic stimulation. Also, leads to an increase in EF, SV, & longevity?

Back 31

Carvedilol

Front 32

Other than preventing cardiac remodeling what other effects does Carvedilol have in patients with HF?

Back 32

1. Decreases sudden death by preventing ventricular dysrhythmias

2. Antianginal effect

Front 33

Carvedilol is approved for use in patients with NYHA class ___ & ___ HF and an EF < than ____.

Back 33

II & III

35%

Front 34

Carvedilol is use to treat HF patients already taking what drugs?

Back 34

1. ACE Inhibitor
2. Diuretic

Front 35

Why should a patient be within 2-3 lbs of "dry" weight (not volume expanded) before starting Carvedilol?

Back 35

Severe pulmonary edema could result

Front 36

How long does it take for EF to increase above pretreatment value in patients taking Carvedilol?

Back 36

Several Months--pt. will feel much better and have increased ability to exercise

*@ 1st beta-adrenoceptor blockade will cause EF to fall & the patient will feel much worse for several months

Front 37

Carvedilol decreases death from LV failure by ______%

Back 37

50+

Front 38

Are the beneficial effects of Carvedilol dose related?

Back 38

Yes, use the largest dose that can be tolerated!

Start w/ a small dose and slowly increase dose

Front 39

What specific cardiac receptors are blocked by Carvedilol?

Back 39

alpha-1, beta-1, beta-2

Front 40

What drug decreases pulmonary congestion by increasing EF & SV & has a marginal effect on longevity, but does NOT reverse cardiac remodeling?

Back 40

Digoxin

Front 41

Digoxin's GENERAL MOA is?

Back 41

positive inotropic effect

Front 42

What are the indirect effects of Digoxin?

Back 42

Acts w/in the CNS to:
1. Enhance the efferent vagal activity:
*slows heart rate
*decreases the # of signals passing through the AV node by decreasing conduction velocity & increasing the ERP

2. reduce efferent sympathetic activity
*decreases automaticity
*increases the ERP in the myocardium

Front 43

When do the adverse direct effects of Digoxin occur?

Back 43

When the plasma concentration falls above the therapeutic window

Front 44

What are the adverse effects of Digoxin?

Back 44

Inhibition of Na/K ATPase:
1. decreases the phase 4 membrane potential difference--cell is closer to threshold
2. produces spontaneous depolarizations in phase 4 leading to premature atrial contractions (PACs) & PVCs; increased intracellular Ca2+ increases the probability of phase 4 automaticity

Increases intracellular Ca2+ also increases the possibility of having delayed after-depolarizations which trigger dysrhythmias

Front 45

What are the therapeutic uses of Digoxin?

Back 45

1. Treatment of HF associated w/ systolic dysfunction when a pt. being treated w/ an ACE inhibitor and diuretic drugs is still symptomatic

2. Treatment of HF in patients with atrial fibrillation because the increase in vagal tone caused by Digoxin controls ventricular heart rate in the presence of a high atrial rate & digoxin enhances ventricular contractility

Front 46

Digoxin:

Therapeutic window?
t1/2 ?
Clearance?
Storage in body?

Back 46

TW: small = 1-2 ng/mL

t1/2: 24-48 h

Clearance: excreted unchanged, proportional to GFR

Storage: stored in skeletal muscle--dose should be based on lean body mass

Front 47

What are the drug-drug interactions of Digoxin?

Back 47

1. Cholestyramine, colestipol, antiacids decrease GI absorption

2. Spironolactone--decreases the renal clearance of digoxin

Front 48

What are the adverse cardiac effects of Digoxin?

Back 48

1. Sinus bradycardia from increased vagal tone
2. AV block via increase vagal tone
3. PACs
4. PVCs & late after-depolarizations

Front 49

What factors precipitate the adverse electrical effects of Digoxin in the heart?

Back 49

1. Hypokalemia--favors the phosphorylated state of ATPase and thus increases the binding of Digoxin to the Na+/K+ ATPase

2. Hypomagnesemia

3. Hypercalcemia

Front 50

Drugs which cause ____________ such as Furosemide, HCTZ potentiate the adverse cardiac effects of digoxin.

Back 50

Hypokalemia

Front 51

What drugs enhance bradycardia and the decrease in AV conduction produced by Digoxin?

Back 51

Calcium channel antagonists:
1. Verapamil
2. Diltiazem

Beta-blockers

Front 52

Why must the left ventricle relax rapidly during systole?

Back 52

To accomodate the normal venous return which loads the ventricle prior to the next systole

Front 53

The early phase of diastole involves (active/passive) relaxation of the LV wall, and the late phase of diastole involves (active/passive) relaxation which depends on ventricular compliance.

Back 53

1. Active
2. Passive

Front 54

How does the heart increase pulmonary perfusion and cardiac output during exercise?

Back 54

Everything in the normal heart speeds up:
-energy-dependent contraction (systole) occurs faster
-energy-dependent relaxation (diastole) occurs faster

Front 55

If the rates of active and passive relaxation of the LV during diastole do not increase during exercise, the heart cannot use the ___________ to increase cardiac output

Back 55

Starling mechanism

Front 56

What are the major diseases which cause diastolic dysfunction?

Back 56

1. Hypertension
2. CAD
3. Aortic stenosis

Front 57

Diastolic dysfunction can be prevented by:

Back 57

1. treating hypertension to prevent or reverse LV hypertrophy

2. treat the ischemia caused by CAD with antilipemic drugs, antianginal drugs, or CABG

3. Valve replacement in aortic stenosis

Front 58

True/False Diastolic dysfunction can't occur in the absence of Systolic dysfunction

Back 58

False

*Diastolic dysfunc. CAN occur in absence of systolic dysfunction

Front 59

True/False Patients with systolic dysfunction always have some diastolic dysfunction

Back 59

True

Front 60

What is the goal of therapy for diastolic dysfunction?

Back 60

Increasing the ability of the LV to relax correctly & fill with blood at a normal filling pressure

Front 61

Systolic and diastolic dysfunction cannot be distinguished on the basis of:

Back 61

History
Physical Exam
ECG
Chest X-ray

Front 62

Diastolic dysfunction is diagnosed based on _____________

Back 62

Doppler echocardiography

*In diastolic dysfunction, the E & A waves representing transmitral inflow velocity are abnormal

Front 63

The clinical hallmarks of heart failure caused by diastolic dysfunction are:

Back 63

1. Pulmonary congestion (dyspnea)
2. Decreased exercise tolerance despite the fact the EF is > 50%

Front 64

The deposition of fibrillar collagen in the ECM of the heart impairs the (active/passive/both active and passive) phases of diastolic relaxation.

Back 64

Both active and passive

Front 65

Decreased LV compliance dictates that a (lower/higher) than normal pressure is required to fill the ventricle with its normal volume during diastole.

Back 65

Higher

Front 66

At the end of diastole, LV pressure is abnormally (high/low) despite the fact that the volume is normal.

Back 66

High

Front 67

Diastolic dysfunction prevents increased cardiac output during exercise via the Startling mechanism because:

Back 67

1. diastolic relaxation does not speed up as heart rate increases

2. ventricular stiffness prevents the increased preload from increasing LV-EDV, so SV cannot increase

Front 68

Treatment of diastolic dysfunction is aimed at:

Back 68

1. relieving symptoms by decreasing pulmonary venous pressure at rest and during exercise

2. reversing LVH: increases ventricular compliance & produces better diastolic filling

3. reversing the remodeling of the ECM of the LV: blockade of cardiac aldo recp increases ventricular compliance and filling

4. decreasing heart rate in order to prolong diastole and this allow better filling of the LV

5. preventing myocardial ischemia; ischemia makes the ventricular wall stiffer
5.

Front 69

Why should diuretic drugs be used with great care to decrease LV diastolic pressure and pulmonary pressure?

Back 69

1. small doses must be used to prevent hypotension and fatigue

2. these patients have high filling pressure or increased blood volume in order to fill the left ventricle normally and this provide a normal preload to maintain CO

3. if LA pressure is decreases too much (nitrates) or if blood volume is decreased too much (diuretic drugs), then inadequate LV filling results in decreases CO which in turn causes hypotension and fatigue

Front 70

Left ventricular hypertrophy can be reversed with an _______ or an ______

Back 70

1. ACE inhibitor
2. Angiotensin receptor antagonist

Front 71

Treatment with ____________ or ___________ inhibits cardiac collagen synthesis & reverses the cardiac fibrosis caused by aldosterone. Decreased fibriosis increases ventricular _____________.

Back 71

1. Spironolactone
2. Eplerenone
3. Compliance

Front 72

For treating diastolic dysfunction use ____________ to decrease basal heart rate prolong diastolic filling

Back 72

Beta-blockers

Front 73

Prolongation of diastole allows more complete relaxation between beats and thus decreases _____________ and an increase in the length of diastole improves endocardial perfuison.

Back 73

LV-EDP

Front 74

Is Digoxin used to treat diastolic heart failure?

Back 74

NO

-significant toxicity
-beta blocker can decrease HR with much less toxicity

Front 75

Cardiogenic shock occurs in about 8% of patients with MI and occurs when _____% or more of the LV muscle is destroyed

Back 75

40

Front 76

Symptoms of cardiogenic shock include:

Back 76

1. Hypotension
2. Tachycardia
3. Tissue hypoperfusion: cold, clammy skin; decreases urine output; altered mental state
4. Pulmonary edema