Pharmacological Management of Heart Failure Flashcards
1
Q
“Living Long” & Feeling Better
A
- Reducing progression
- Neurohormonal interventions
- Introduce disease modifying therapies that alter disease course
- Preventing complications
- Not directly related to heart failure as a pump
- Stroke & arrhythmias
- Hemodynamic interventions
- Reduce volume overload &/or increase amount of blood pumped by the heart
2
Q
Pathological Progression of CV Disease
A
- Heart failure continues to progress even after the initial insult is over
- Ex. a patient has a large anterior wall MI that she survives, & she never has an MI again
- Initially, she will get better b/c once-stunned (not dead) myocardium recovers
- However, her LV function, LV size, & clinical status will continue to deteriorate due to progressive LV remodeling
3
Q
Heart Failure Pathophysiology
A
- Heart failure is progressive
- There are several pathwayts playing roles in CHF
- Activation of these pathways causes CHF to worsen –> vicious cycle
- This is what you have to interrupt to treat heart failure
4
Q
Classificaiton of HF
- ACC/AHA Stage
- NYHA Functional Class
A
- ACC/AHA Stage (cannot go back a stage)
- A: at high risk for HF w/o structural heart disease or symptoms
- HTN, atherosclerotic disease, diabetes mellitus, CAD, FH, cardiotoxic drugs
- 1 year mortality = 2-3%
- B: structural heart disease (LV dysfunction) w/o HF symtpoms
- LVH, MI, low LVEF, dilation, valvular disease
- 1 year mortality = 5-10%
- C: structural heart disease (LV dysfunction) w/ prior or current HF symptoms
- 1 year mortality = 15-30%
- D: refractory HF requiring specialized interventions (severe CHF)
- Many symptoms, recurrent hospitalizations
- 1 year mortality > 50%
- A: at high risk for HF w/o structural heart disease or symptoms
- NYHA Functional Class (can go back a stage)
- 0: none
- I: asymptomatic
- II: symptomatic w/ moderate exertion
III: symptomatic w/ minimal exertion - IV: symptomatic at rest
5
Q
Neurohormonal Acitvation in HF
- 2 major pathways involved in disease progression
- Disease progression
A
- 2 major pathways involved in disease progression
- Angiotensin II
- Angiontensin pathway:
- Angiontensin II binds to AT1
- Cascade –> increased hypertorphy, vasoconstriction, & NA/water retention in the periphery
- Norepinephrine
- Angiotensin II
- DIsease progression
- Hypertrophy
- Apoptosis
- Ischemia
- Arrhythmias
- Remodeling
- Fibrosis
6
Q
ACE Inhibitors (ACE-Is)
- Effects
- Clinical effects
- ACE-I continuum
- Side effects
A
- Effects
- Block conversion of angiotensin I to angiotensin II
- Decrease afterload
- Lower angiotensin II 9transiently)
- Lower neurohormones
- Decrease fibrosis
- Prevent progressive remodeling
- Clinical effects
- Improve symptoms & quality of life
- Improve exercise tolerance
- Improve ejection fraction
- Reduce hospitalization
- Reduce mortality
- ACE-I continuum
- ACE-Is are indicated across the entire spectrum of CHF
- (1) at risk
- (2) asymptomatic LV dysfunction
- (3) symptomatic LV dysfunction
- (4) severe CHF
- Ex. captopril (short acting) & enalapril (long acting)
- ACE-Is are indicated across the entire spectrum of CHF
- Side effects
- Cough
- Most common reason why ACE-Is are stopped
- Mediated by bradykinin
- Most common cause of cough: CHF itself
- Ensure the patient isn’t volume overloaded & doesn’t have a URI
- Worsening renal function (usually only w/ significant renovascular disease)
- Another mage cause of stopping ACE-Is
- Ensure there’s not another cause of renal failure (ex. dehydration)
- Important cause of worsening renal function: NSAID use
- Hyperkalemia
- Ensure the cause isn’t K supplementation
- Angioedema
- Absolute contraindication
- Overall: there are major benefits of ACE-Is in CHF, so make sure they’re not stopped for the wrong reason
- Cough
7
Q
Angiotensin Receptor Blockers (ARBs)
- Effects of adding candesartan or valsartan
- ARBs vs. ACE-Is
A
- Effects of adding candesartan or valsartan
- Reduce death or hospitalizations
- Possibly reduce deaths
- Can increase risk of nephrotoxicity & hypotension
- ARBs vs. ACE-Is
- ARBs are equivalent (but not superior to & more expensive than ACE-Is
- Primarily used in ACE-I intolerant patients
- Used in patients w/ current or prior CHF symptoms as a result of LV
- Used in patients w/ ACE-I related cough since ARBs don’t upregulate bradykinins
- ARBs also cause renal failure, hyperkalemia & angioedema
- ARBs aren’t indicated when ACE-Is cause renal failure or hyperkalemia
8
Q
Aldosterone Escape
- Aldosterone escape
- Effect of eplerenone immediately after MI
- Effect of spironolactone in moderate & severe CHF
- Aldosterone antagonists
A
- Aldosterone escape
- Aldosterone levels may fall initially in response to ACE inhibition or angiotensin II receptor blockade
- But they return to normal (“escape”) by 12 weeks
- Effect of eplerenone immediately after MI
- Reduces mortality
- Effect of spironolactone in moderate & severe CHF
- Substantial benefit
- Aldosterone antagonists
- Should be part of routine CHF management for anything more than “at risk” patients
9
Q
Aldosterone Blockade
A
- Clearly indicated in class 3 to 4 heart failure
- 12.5 to 25 mg QD spironolactone
- Spironolactone is cheaper & should be the first choice
- Need to watch K closely
- Particularly on ACE-Is or K supplementations
- Generally cut K supplements in half when initiating
- Gynecomastia / mastalgia may occur w/ spironolactone switch to eplerenone
- Consider use when K requiremetns are high
10
Q
Effects of NE in CV Disease
- Sympathetics
- NE vs. mortality in patients w/ CHF
A
- Sympathetics
- Essential in maintaining cardiac output when this drops acutely
- Good b/c the most common cause of an acute drop in CO is traumatic blood loss
- The heart pumps more, blood vessels constrict to divert blood to vital organs, & kidneys retain more fluid & water
- Sympathetic overdrive may keep you going for some time, but over time will lead to bad things
- NE vs. mortality in patients w/ CHF
- More sympathetically “hyper” patient –> worse patient will do w/ high NE levels
- Damage caused by sympathetic activation is persistent: effect increases w/ time
11
Q
Beta Blockers
- Continuum (class effect)
- Clinical effects
- Contraindications
- Effect of ACE-Is & beta blockers on ventricular remodeling
A
- Continuum (class effect)
- Carvedilol: only bet ablocker that benefits severe CHF b/c it’s a non-selective beta blocker that also has some alpha blocking activity
- Use carvedilol in severe CHF or in CHF w/ HTN b/c it’s a better antihypertensive agent than selective beta blockers
- Clinical effects
- Improve symptoms & quality of life
- Improve ejection fraction
- Prevent progressive remodeling
- Reduce hospitalizations
- Prlong survival & reduce sudden death
- May transiently worsen symptoms
- Worsening LV function & cardiac output
- Fatigue (gets better in 1-2 weeks)
- Fluid retention (may require temporary increase in water pills)
- Contraindications
- Active volume overload
- This will get worse, so wait until they’re dry before starting or increasing
- Hypotension
- Bronchospasm
- Asthma & COPD (use iwth caution)
- Bradycardia
- Particularly symptomatic or high degree AV block
- Less of an issue since most patients get ICDs
- Active volume overload
- Effect of ACE-Is & beta blockers on ventricular remodeling
- ACE-Is stop the progressive LV dilation of CHF
- Beta blockers stop & might reverse adverse remodeling
12
Q
Beta Blockade
- Beta blockers paradox
- Beta blockade in patients w/ CHF & post-MI LVD
- Beta blockade can be used safely in the majority of CHF patients who…
A
- Beta blockers paradox
- Initial negative inotropy is balanced by enhanced myocardial recovery
- Blocking sympathetic overdrive w/ beta blockers in subjects w/ CHF could initially reduce cardiac output, but over time, the heart would perform better w/ beta blockers
- Beta blockade in patients w/ CHF & post-MI LVD
- Beta blockers reduce mortality in CHF by mechanisms other than stopping remodeling (ex. reducing deaths from arrhythmias)
- Beta blockade can be used safely in the majority of CHF patients who…
- Are free of volume overload when beta blockade is started
- Have a systolic BP > 90 mmHg & HR > 60
- Don’t have bronchospasm
13
Q
NO Paradigm in HF
- Vasoconstricting & growth promoting systems
- Vasodilating & growth inhibiting systems
A
- Vasoconstricting & growth promoting systems: worsen hemodynamics & progress remodeling
- NE
- Angiotensin II
- Endothelins
- Arginine vasopressin
- Vasodilating & growth inhibiting systems: improve hemodynamics & prevent remodeling
- Natriuretic peptides
- Bradykinin
- NO
14
Q
Consequences of Nitric Oxide & Super Oxide Balance Disruption in Heart Failure Patients
- Effects of NO in CHF
- Effects of free radicals in CHF
- Effects of nitrates + hydralazine in CHF
A
- Effects of NO in CHF: beneficial
- Direct effects on contractility
- Inhibits apoptosis
- Promotes vasodilation
- Effects of free radicals in CHF: detrimental
- Damage DNA
- Effects of nitrates + hydralazine in CHF: beneficial
- Nitrates stimulate the production of NO
- Hydralazine inhibits the oxidase (free radical) pathway
- Can induce lupus via anti-histone antibodies
- Primary use: ACE/ARB intolerant patients w/ renal dysfunction
- Both decrease BP, so use w/ caution
15
Q
Preventing Stroke
A
- Risks
- Patients w/ LV dysfunction (particularly w/ large anterior wall MIs) are at risk for LV thrombus formation
- CHF patients are also at risk for atrial fibrillation
- Anticoagulation
- Consider anticoagulation w/ warfarin in all patients w/ anterior wall MIs or w/ EF < 20% (contraversial)
- Treat afib w/ warfarin unless contraindicated
19
Q
Compensatory Mechanisms: Frank-Starling Law
- X-axis: LVEDP = filling pressure
- Y-axis: cardiac index (cardiac output / body surface area)
- Curved lines: how the cardiac index behaves as filling pressure increases
- This plot classifies the hemodynamic problem in each patient w/ CHF
A
- X-axis: LVEDP = filling pressure
- Normal < 12
- Patients start feeling short of breath as LVEDP increases
- Back pressure in the pulmonary capillaries –> fluid leakage & edema
- This starts happening at different pressures depending on various factors
- Most common factor: how long the patient has had high pressure
- Most common pressure when patient starts feeling it: 18 mmHg
- Y-axis: cardiac index (cardiac output / body surface area)
- Normal > 2.2 lt/min/m2
- Curved lines: how the cardiac index behaves as filling pressure increases
- All of this gets worse with exertion
- Severe cases: patients have high enough pressures to cause pulmonary edema to get close to a normal resting cardiac index
- For the same cardiac output, a patient w/ LV dysfunction has to have a higher filling pressure
- For the same pressure, patients w/ LV dysfunction generate a lower cardiac output
- This plot classifies the hemodynamic problem in each patient w/ CHF
- Class I: normal output & normal pressures
- Class IV: can’t get a normal cardiac index despite high filling pressures
20
Q
Forrester Hemodynamic Subsets
- For each subset:
- I: Warm Dry
- II: Warm Wet
- III: Cold Dry
- IV: Cold Wet
- Characteristics
- LVEDP
- Cardiac index
- BP
- JVP
- Lungs
- Extremities
- Creatinine
- Cardiac output
- Filling pressures
- Therapy
A
- Criteria
- Wet = filling pressures are high from fluid overload
- Cold = cardiac output is reduced & patients look & feel cold
- I :Warm Dry
- LVEDP: low
- Cardiac index: high
- BP: normal
- JVP < 5cm
- Lungs: clear
- Extremities: no/trace edema
- Creatinine: normal
- Cardiac output: normal
- Filling pressures: normal
- Therapy: none
- II: Warm Wet
- LVEDP: high
- Cardiac index: high
- BP: normal
- JVP > 5cm
- Lungs: crackles
- Extremities: ++ edema
- Creatinine: normal
- Cardiac output: normal
- Filling pressures: high
- Therapy: diuretics
- III: Cold Dry
- LVEDP: low
- Cardiac index: low
- BP: low
- JVP ~ 5cm
- Lungs: minimal crackles
- Extremities: no/trace edema
- Creatinine: increased
- Cardiac output: low
- Filling pressures: normal
- Therapy: adjust medical tehrapy
- IV: Cold Wet
- LVEDP: high
- Cardiac index: low
- BP: low
- JVP >> 5cm
- Lungs: ++ crackles
- Extremities: ++ edema
- Creatinine: increased
- Cardiac output: low
- Filling pressures: high
- Therapy: inotropes, IABP, VAD/transplant
21
Q
Diuretics
- Loop diuretics
- Thiazides
- CHF patients are tenuous
A
- Loop diuretics
- Primary agents used in CHF
- Potent agents that can cause profound diuresis
- Thiazides
- Added for synergy when loop diuretics aren’t enough
- Aldosterone antagonists: potassium sparing thiazides
- CHF patients are tenuous
- When a person w/ a normal cardiac function has a lot of volume “room” to play with before becoming dehydrated or volume overloaded, it takes much less for a patient w/ CHF to “get into trouble”
- Frequent monitoring of renal function & electrolytes is essential
22
Q
Digoxin
- General
- General effects
- Parasympathetic effects
- Electrophysiological effects
- Clinical effects & use
- Side effects
- Cardiac
- CNS
- GI
- EKG abnormalities
A
- General
- One of the oldest drugs
- Inhibits of Na/K ATPase
- Increases intracellular Ca2+ to increase contractility
- Blunts Ca2+ extrusion
- Increases Ca2+i
- Enhances sarcomere shortening
- General effects
- Increase cardiac output
- Improve cardiac efficiency
- Decrease heart rate
- Decrease cardiac size
- Restore baroreceptor sensitivity
- Reduce sympathetic activity
- Increase renal perfusion
- Parasympathetic effects
- Decreases conduction velocity in the AV node
- Increases effective refractory period in the AV
- Heart block (toxic concentrations)
- Electrophysiological effects
- Less negative membrane potential –> decreased conduction velocity
- –> increased chance of ectopic beats & other arrhythmias
- Decreased action potential duration –> decreased refractory period in ventricles
- Enhanced automaticity due to steeper phase 4 & after-depolarizations
- Less negative membrane potential –> decreased conduction velocity
- Clinical effects & use
- Improves symptoms only
- Reduces hospitalizations
- Used in CHF & atrial fibrillation
- Narrow therapeutic window (esp in elderly & paitents w/ renal impairment)
- Doesn’t reduce & may increase mortality (esp in elderly)
- Side effects
- Cardiac
- Atrial tachycardias
- AV block
Bradycardia - Ventricular extrasystole
- Arrhythmias
- CNS
- Visual halo
- Yellow vision
- GI
- Nausea
- EKG abnormalities
- T wave inversion
- Decrease RT interval
- Uncoupled P waves (toxic concentrations)
- Bigeminy (toxic concentrations)
- Cardiac
23
Q
Inotropes
- Use
- Effects
- Classes
- Indications
- Signs of severely decreased cardiac output
- Signs of refractory volume overload
- Complications
A
- Use
- Patients must exhibit both cold (decreased cardiac output) & wet (volume overload) symptoms to justify use
- Effects
- Blunt response to increased filling pressure –> increased volume isn’t enough to maintain adequate response
- Inotropes increase contractility to maintain adequate response
- Classes
- Direct beta agonists (vasodilators, stop beta blockers before using)
- Dobutamine
- Epinephrine
- Phosphodiesterase inhibitors (increase intracellular Ca2+)
- Milrinone
- Enoximone
- Direct beta agonists (vasodilators, stop beta blockers before using)
- Indications: palliation
- Signs of severely decreased cardiac output
- Hypotension
- Increasing renal insufficiency
- Mental status changes
- Severe fatigue
- Signs of refractory volume overload
- Lung congestion
- Peripheral edema
- JVP
- Signs of severely decreased cardiac output
- Complications
- Hypotension
- Sinus tachycardia
- Atrial fibrillation
- Ventricular ectopy / tachycardia
- Worsening ischemia (by increasing myocardial work / O2 demand)
- Death (all agents increase mortality)
