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176 Cards in this Set

  • Front
  • Back
CO=
HR x SV
what components control SV?
preload
afterload
contractility
dilating arteries decreases_______.
(preload, afterload, contractility)
afterload
preload
-ventricular wall stress at the end of diastole
-myocardial stretch or fiber length at the end of diastole
-approximated by end diastolic volume of pressure
-as fiber length increases, CO increases
frank stRLING CURVE
afterload
-systolic ventricular wall stress
-resistance ventricles must overcome to empty
-arterial systolic pressure
-increased PVR= increased afterload
frank starling curve: an increase in afterload will _____
(shift curve up, down, no change)
shift curve down (MI also shifts curve down)
contractility
-inotrpoic state
-independent of preload and afterload
-changes shift curve up or down
what does a Beta agonist do to the FS curve?
shift up; curve lies between normal and HF w/o Beta agonist
HF contributoirs
-pressure overload
-volume overload
-loss of fnx myocardial tissue
-decreased contractility
-restricted filling
two types of HF
- reduced LVEF
- preserved LVEF
left sided failure
lung edema
rightr sided failure
peripheral edema
what are the compensatory systems activaed with reduced CO
RAAS and SNS
ANG II
-more aldosterone
-more vasopressin
-more SNS firing
-more endothelin
2 states of HF
-stable chronic HF
-acute decompensation
stable chronic HF
symptoms under control
acute decompensation
something triggers a 'relapse', ie back to hospital time
how does the heart increase ejection fraction?
-increase contractility
-increase preload
-decrease afterload
why do oyou not want to increase preload in HF?
it will increase edema
what does excess neurohumoral activation on the heart cause?
cardiac remodeling:
-hypertrophy
-fibrosis
-apotptosis
-ventricual dilation
-fetal gene expression
** culprits: NE, Ang II, aldosterone
Stage A HF
high rish of deveoping;; no structural disorder
Stage B HF
structural disorder without HF symptoms
Stage C HF
symptoms of HF wiyth underlying heart Dz
Stage D HF
end-stage Dz requiring specialized Tx
NYHA classes of HF
-Class 1 (mild)
no limits on physiucal activity
-Class 2 (mild)
slight limits
-Class 3 (moderate)
marked limitation
-Class 4 (severe)
symptoms at rest
Consequences of Activation of Adrenergic and the Renin- Angiotensin-Aldosterone System in Heart Failure
Ms. Heddy Fail, a 68-year-old female, has a high risk for developing HF (eg atherosclerosis, diabetes mellitus), but does not have a structural disorder (eg no LVH). What will we use to treat her heart failure?
Stage A: ACEi or ARB
ACEis
prils
ACEi action
What effect will ACE
inhibitors have on arteries?
vasodilation due to increased bradykinin and decreased Ang II
what happens to Ang II levels after a while with ACEis?
may normalize. Na and water loss with ACEis is not sufficient to alleviate edema associated with HF...
and after several months aldosterone levels are elevated
Ang II and cardiac remodeling
ACEi benefits in HF
-decrease afterload
-possibly some decrease in preload
-PREVENT REMODELING
ACE Inhibitor: End Result
Prolong exercise tolerance
Increase quality of life
Decrease hospital readmissions for heart failure
Decrease morbidity and mortality
ACE Inhibitor: Clinical Use
Certain patients at risk for HF:
-Stage A
-Hx os atherosclerotic vascular Dz, Db mellitus, or HTN and associated risk factors
Certain patients with asymptomatic LV systolic dysfnx:
-Stage B
-any Hx of MI
-reduced EF
-HTN and LVH
All patients with heart failure to to left ventricular systolic dysfnx should receive a _____ unless contraindicated or not tolerated
ACEi; Stage C and D; NYHA class I-IV
Start at low does and titrate up every 3-7 days to dose achieved in clinical trials
A patient presents in the emergency room complaining of dyspnea and fatigue. They have a history of heart failure that is being treated with a diuretic and digoxin. Physical exam reveals a blood pressure of 80/50 and pulmonary edema. Laboratory tests reveal a serum creatinine of 2.5 mg/dL (normal 0.8-1.2 mg/dL). Would you give them an ACE inhibitor?
Yes, right away
No, not now
No, not now
ACEi AEs: Biggest concerns for heart failure
-Hypotension
-Worsening renal fnx
-Hyperkalemia
**rest: see HTN lectures
Ang II Receptor Antagonists (ARBs)
-sartans
what are the advantages of ARBs over ACEis?
no/less cough and angioedema
what are the disadvantges of ARBs?
-Bradykinin (growth inhibitor and vasodilator) is still broken down
-less clinical experience with ARBs than ACEis
ARB clinical use
-alternative to ACEis for HF
-No differences found between ACEis and ARBs in terms of all-cause mortality, sudden cardiac death, or resuscitated cardiac arrest, or hospitalizations.
Beta blockers
-sustained release Metoprolol
-Bisoprolol
-Carvedilol
Beta 1 selective antagonists
-Metoprolol
-Bisoprolol
Carvedilol
-blocks β1, β2 & α1 Rs
-ratio of bloackade β1:β2:α1= 10:10:1
-antioxidant effects
beta blocker Mechanism of Action in Heart Failure
unknown
--Over stimulation of the SNS in heart failure is thought to contribute to mortality
detrimental effects of excessive SNS activation on the heart
More Detrimental Effects of Excess SNS Activation in HF
-Selective down regulation of b1 receptors
-Increased renin release
-Na and water retention
-Tachycardia and arrhythmias
Beta blockers:
Mechanism of Action in Heart Failure – Some Theories
**Prevent or reverse cardiac hypertrophy and remodeling
-Prevent b1 receptor down regulation
-Correct impaired intracellular Ca2+ handling
-Decrease cardiac workload
Decreased heart rate
Decreased secretion of renin
**Prevent atrial/ventricular arrhythmias
Beta blockers: Results of clinical studies involving more than 20,000 patients
-Increase left ventricular ejection fraction (long term)
-Decrease ventricular volume (pumping more out)
-Lessens symptoms of heart failure
-Decrease hospitalization for worsening HF
-Decrease mortality
Beta blockers: clinical use 1.
-Certain patients with asymptomatic LV systolic dysfunction
--Stage B
--All patients with history of myocardial infarction
--All patients with reduced ejection fraction
Beta blockers: clinical use 2.
-All patients with STABLE heart failure due to left ventricular systolic dysfunction should receive a b blocker unless contraindicated or not tolerated
--Stage C and D
--NYHA Class I-IV
Does this mean you will use a b blocker in all Stage IV patients?
no, not everyone can tolerate them
Beta blockers: clinical use 3.
-stat at ow doses and titrate up every few weeks
--benefit not immediate
--titrated to target doses determined from clinical trials rather than clinical effect
Initial and Target Doses for b-blockers in HF
Beta Blockers: more clinical use :)
-May have particular benefit in diabetics
-Use in conjunction with ACE inhibitors
-Carvedilol and metoprolol – FDA approved for heart failure
A heart failure patient has mild symptoms that are controlled with enalapril and furosemide. Should a b blocker be added to their treatment regimen?
yup... reduce mortality
Beta blockers: AEs
**Fluid retention and worsening heart failure
--Initiation of therapy or after increasing dose
-Fatigue
-Bradycardia and heart block
-Hypotension
**Abrupt withdrawal can cause deterioration of cardiac function
**see antiHTN lectures for rest
Beta blockers: contraindications 1.
-Acutely decompensated heart failure
--Wait until patient is stable before starting a b blocker
-Symptomatic bradycardia or heart block without a pacemaker
is diabetes a contraindication for Beta blockers in HF?
nope
Beta blockers: contraindications 2.
-Reactive airway disease that requires inhaled b agonist therapy
-Fixed airway diseases such as chronic obstructive pulmonary disease is NOT necessarily a contraindication
What do you do when a patient with HF that has been taking b blockers chronically presents in the hospital with decompensation? Keep them on the b blocker or take them off?
keep them on... stop or reduce in patients hospitalized after recent initiation
Ms. Heddy Fail’s heart failure is getting worse because she just had an episode of pulmonary edema. Remember before that she had left ventricular hypertrophy and a reduced ejection fraction. What will you use to treat her heart failure?
Stage C
-ACEi
Beta blocker
Loop D (HF edema)
Diuretic classes
Loop diuretics
Thiazide diuretics
Potassium sparing diuretics
What effect will this have on preload?
decrease
If you reduce preload what happens to pulmonary edema?
decrease
What effect will diuretics have on CO in a patient with heart failure?
increase
decrease
little/no effect
little/no effect: frank starling- shift left but SV no change. curve is already pretty flat cuz it cant squeeze too good
diuretrics: end result
-Reduce pulmonary and peripheral edema without adversely affecting CO
-The decrease in wall stress may also slightly improve systolic function
Which class of diuretics is most useful in the treatment of edema associated with heart failure
loops
Loop and Thiazide Diuretics: clinical use
-Prevent or treat fluid retention from HF
--Stage C and D
-Mainly use loop diuretics
-Add a thiazide diuretic if refractory to the loop diuretic
-These are the only drugs that can adequately control fluid retention
-No known effect on morbidity and mortality
Loop and Thiazide Diuretics: AEs
-Volume depletion
-Hypotension
-Worsening renal function
-Hypokalemia
--Especially important if on Digoxin
**see diuretic lectiures for rest
What is one of the major problems associated with K+ depletion?
can predispose to arrhythmia
How do you prevent the hypokalemia associated with loop or thiazide diuretics?
K+ sparing diuretics btches!
K+ sparing diuretics: clinical use
prevent hypokalemai assoc with loops and thiazides
Spironolactone
Eplerenone
who is the secret enemy of the heart?
aldosterone btches!
Aldosterone and Heart Failure
-Aldosterone levels may be 20X greater in patients with heart failure
-ACE inhibitors may only produce a transient decrease in aldosterone levels
Pathophysiological Effects of Aldosterone…
Theory: Blocking aldosterone receptors on the heart/blood vessels is _______
cardioprotective
Aldosterone and Heart Failure: Randomized Aldosterone Evaluation Study (RALES)
-Added spironolactone to conventional therapy in patients with severe HF (NYHA class III or IV)
--ACE inhibitor, loop diuretic + digoxin
--About 10% were on a b blocker
-Decreased mortality
-Decreased hospitalization for HF
-A very low risk of hyperkalemia
Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS)
Patients post AMI complicated by LV dysfunction and HF
Severity of HF was less than in RALES
75% received b blockers vs 10% in RALES
15% reduction in mortality
15% reduction in hospitalizations for HF
21% fall in sudden cardiac death
Aldosterone Antagonists: clinical use
-Selected patients with moderately severe to severe symptoms of HF and recent decompensation or with LV dysfunction early after an MI
-Stage C, NYHA Class III-IV
-Must monitor renal function and potassium concentrations
-Decreases hospitalizations!
-Decreases mortality!
A patient has Stage C, NYHA Class III HF. If their serum creatinine is > 2.5 mg/dL (normal 0.8-1.2 mg/dL), would you use an aldosterone antagonist?
yes or no
no
A patient has Stage C, NYHA Class III HF. If their serum K is 3.6 mEq/L (normal 3.5 - 5.0 mEq/L), would you use an aldosterone antagonist?
?
What do the guidelines say?
-To minimize the risk of life threatening hyperkalemia
--serum creatinine less than 2.0 (female) to 2.5 (male) mg/dL
--serum K less than 5.0 mEq/L
What happened after RALES?
Prescriptions for spironolactone rose dramatically (5 fold from 30/1000 patients in 1999 to 149/1000 patients in 2001)
Admissions for hyperkalemia increased (about 3-4 fold)
Rate of in-hospital deaths from hyperkalemia increased (about 2-3 fold)
No change in rate of readmission for heart failure
What is the advantage in using spironolactone vs eplerenone?
spironolactone blocks androgen Rs, man boobs bro.
Spironolactone and Eplerenone: AEs
-Fluid depletion
-Renal dysfunction
-Hyperkalemia
**see diuretic lectures for rest
Ms. Heddy Fail complains of being pretty fatigued with short walks. She has had to go into the hospital several times for her heart failure. Remember she has Stage C HF. She is on ramipril, metoprolol, eplerenone, and furosemide. What will you use to treat her heart failure?
stage c
ramipril
metoprolol
eplerenone
digoxin
Digitalis Glycosides
Digoxin (Lanoxin)
Digitoxin (Crystodigin)- rarely used
review of cardiac electrophys: depolarization
L-type Ca2+ channel: voltage gated; opens Ca induced Ca2+ channel (ryanadine Rs)
Review of Cardiac Electrophysiology: depol summary
Opening of Na channels on the membrane causes cardiac myocyte depolarization
This activates voltage gated Ca channels and calcium enters the cell
This ‘trigger’ Ca activates Ca-induced Ca release channels on the SR
Ca is released from the SR causing an increase in the intracellular concentration of Ca and contraction
Review of Cardiac Electrophysiology: repolarization
Review of Cardiac Electrophysiology: repol summary
During repolarization, Na is extruded from the cell via the Na-K ATPase
Ca is taken back up into the SR via the sarcoplasmic/endoplasmic reticulum Ca-ATPase (SERCA)
Ca is also extruded from the cell by the Na-Ca exchanger and a sarcolemmal Ca-ATPase (not shown in figure)
The Na-Ca exchanger is driven by the transmembrane Na gradient
Digoxin: MOA
digoxin: moa
digoxin: interaction with K+
digoxin: moa summary
Inhibition of the Na-K ATPase raises intracellular Na levels
A higher Na concentration causes less Ca to be extruded from the cell by the Na-Ca exchanger
More Ca is taken up by the SR
There is a larger Ca transient during subsequent contraction
Increased force of contraction
digoxin: interaction with K+: what does hyper and hypokalemia do to the action of digoxin?
-hyperkalemia: reduces the action of digoxin

-hypokalemia: increases action/toxicity of digoxin
wat class of drugs can cause HYPOkalemia
loops and thiazides
Digoxin: indirect effects
-increased vagal activity
-baroreceptor sensitization
-decreased SNS activity
**decreased activity of SA and AV node
Digoxin: toxic effects on the heart
-Low dose: sinus bradycardia, AV block (excess vagal tone)
-High dose: Ca2+ overload and increased SNS tone (centrally induced)
Ca overload
Ca overload
In a damaged heart, what can excessive sympathetic tone and Ca overload cause?
arrhythmias
digoxin: PK`
Absorption
40-90%
Plasma protein binding
25%
Half life
36-48 hours
Excreted unchanged by the kidney
**LOW therapeutic index
digoxin: clinical use
Heart Failure:
--Used in conjunction with diuretics, an ACE inhibitor and a beta blocker
--Initiated after the patient is stabilized
--NO EFFECT ON MORTALITY
--Used to treat symptoms – Stage C and D
is digoxin used for acutely decompensated HF?
no
digoxin: clinical use
-A fib/flutter
-increase vagal activity
-slow ventricular rate
digoxin AEs: arrhythmias
--Increased vagal tone: sinus bradycardia & AV block
--Ca2+ overload/central SNS stim: A tach, PVCs, V tach/fib
digoxin AEs: GI tract
-Increased motility: anorexia, diarrhea
-Chemoreceptor trigger zone (CTZ): nausea, vomiting
what is the first sign of dogoxin toxicity?
CTZ
DIgoxin AEs: CNS
Headache
Fatigue
Drowsiness
Disorientation
Confusion
Hallucinations
**other early sign of digoxin toxicity
Digoxin AEs: visual disturbances
Blurred vision
Green and yellow halos around objects
digoxin AEs: estrogen
gynecomastia
what factors enhance digoxin toxicity?
Hypokalemia
Hypercalcemia
Hypomagnesemia
Digoxin Fab (digibind)
-Digoxin ‘antidote’
-Fab fragment of digoxin-specific antibody
**Decreases free dogixin concentration in the blood
what effect will reducing the free digoxin concentration in blood have?
decreases the amount of digoxin that can bind and inhibit the Na-K ATPase on cardiac myocytes
what is digibind used for?
Life threatening cases of digoxin toxicity
A 58-year-old female presents in her primary care physician’s office complaining of progressive fatigue over the last 3 months. Physical exam reveals a BP of 155/90, pulse 75 bpm. Auscultation of the lungs is unremarkable. Abdominal systolic-diastolic bruits are heard over the flank and a doppler ultrasound reveals narrowing of the renal arteries. Urinalysis reveals a BUN of 19 mg/dL (normal 10-20), and serum creatinine of 1.3 mg/dL (normal 0.5-1.2). An echocardiogram reveals a LVEF of 40%. She takes no medication. What would you use to treat this patient?
Beta blocker, ACEi, Digoxin, Diuretic, or ARB
beta blocker
-not ACEi: renal artery stenosis
-not diuretic cuz theres no edema
-not ARB cuz of renal artery stenosis
Vasodilators
Isosorbide dinitrate
Hrydralazine
isosorbide dinitrate MOA
a decrease in preload does what to edema and wall stress?
decrease both
hydralizine effect on HF
decreased aftrerload has what effect on EF and wall stress?
increased EF, decreased wall stress
hydralizine action on HF
-antioxidant effect
-prolong NO
Isosorbide Dinitrate + Hydralazine: clinical use
-African-Americans with moderate to severe symptoms on optimal therapy with diuretic, ACE inhibitor, b blocker
-In patients who cannot use an ACE inhibitor or ARB
--Stage C patients
-Decreases mortality
*Not as good as ACE inhibitors
What is the goal in the pharmacological treatment of acute decompensated HF?
-Increase CO (probably with loop D)
-Relieve pulmonary congestion
How can pulmonary edema be reduced?
decrease preload: loop D
hydralizine action on HF
-antioxidant effect
-prolong NO
How can cardiac output be increased?
diuretic
venous dilation
Isosorbide Dinitrate + Hydralazine: clinical use
-African-Americans with moderate to severe symptoms on optimal therapy with diuretic, ACE inhibitor, b blocker
-In patients who cannot use an ACE inhibitor or ARB
--Stage C patients
-Decreases mortality
*Not as good as ACE inhibitors
What is the goal in the pharmacological treatment of acute decompensated HF?
-Increase CO (probably with loop D)
-Relieve pulmonary congestion
How can pulmonary edema be reduced?
decrease preload: loop D
How can cardiac output be increased?
decrease afterload
increase contractility (stage D pts)
What are 2 ways to reduce preload?
diuretic
venous dilation
How can afterload be reduced?
arterial dilator
IV drugs for acutely decompensated heart failure
Loop Ds
nitroglycerine
nitroprusside
nesiritide
Mechanism of action of IV loop diuretics in pulmonary edema…
What do you have to be concerned about when using loop diuretics for decompensated HF?
HYPOtension
Renal failure
Hypokalemia
What is the best choice for treating congestion or pulmonary edema in a patient with acute decompensated heart failure?
LOOP D!!!!!!!
What is the best choice for treating congestion or pulmonary edema in a patient with acute decompensated heart failure?
diuretic
Loop Ds: clinical use
IV for acutely decompensated heart failure
-For volume overload
Nitroglycerin, Nitroprusside MOA
Nitroglycerin
-Increases NO mainly in veins
Nitroprusside
-Increases NO in both arteries and veins
NO causes vasodilation
What effect will nitroglycerin have on preload? What about afterload?
decrease preload, not much on afteroad
What effect will nitroprusside have on preload?

What about afterload?
decrease, decrease
Nesiritide
Recombinant human B-type natriuretic peptide (BNP
B-type Natriuretic Peptide
Released from the ventricles in response to increased wall stress, hypertrophy, and volume overload
Nesiritide (Natreco) MOA:
Nesiritide (Natrecor): MOA 2
Nitroglycerin, Nitroprusside, Nesiritide: clinical use
IV for acutely decompensated heart failure
-Added to diuretics for patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension
-Relief of angina (nitroglycerin)
-Control of hypertension complicating HF
Nitroglycerin, Nitroprusside AEs
see HTN and ischemia lectures
Nesiritide AEs
Hypotension
-Possibility of dose-related episodes of severe and/or protracted hypotension

Headache
Worsening renal function????
Possibly increased mortality vs other treatments????
ASCEND-HF
Nesiritide does not compromise renal function or increase mortality within a month of its use in acute decompensated HF
Does not seem to have much more of an effect against acute dyspnea than can be achieved with conventional diuretics and vasodilators
A 76-year-old male presents in the emergency room with dyspnea. Physical exam reveals 2+ pitting edema, blood pressure of 110/80 and bibasilar rales. He has a history of heart failure (Stage C, NYHA Class II) and hypertension. His current medications include furosemide, ramipril and carvedilol. Which drug would most likely treat his acute problems?
digoxin, furosemide, isosorbide dinitrate, metoprolol, nitroprusside, prazosin
give more furosemide
what if that didn't work?
nitroglycerine, nitroprusside, nesiritide
How can pulmonary edema be reduced
decrease preload
How can cardiac output be increased?
decreese afterload
what do we want for stage D pts?
increased myocardial contractility
Dobutamine, Dopamine & Phosphodiesterase Inhibitors
(Inamrinone and Milrinone) are ______ inotropic drugs
positive
dobutamine MOA
dobutamine MOA 2
dobutamine action in HF
dobutamine in HF some more
dobutaine in HF some more
incfreased PVR and BP... bad for heart, but need to raise BP in this instance
phosphodiesterase inhibitors
phosphodiesterase inhibitors: chronic use
Intolerable side effects
-Inamrinone – thrombocytopenia
Both – hypotension, arrhythmias
Minimal long term efficacy
Increased mortality with long term use
PDE 3
increased cAMP: Inamrinone, Milrinone
PDE 5
increased cGMP
Dobutamine, Dopamine, Milrinone
IV infusion – severe, refractory heart failure
-Alleviate symptoms
-Stage D
Once stabilized, wean off of IV drugs
Intermittent infusions of positive inotropic drugs should not be used in the long-term treatment of HF, even in its advanced stages.
what FDA inotropic agents have been shown to reduce mortality and increase survival
none... Patients may take these IV positive inotropic drugs for symptomatic relief but not for long-term benefits.