phm 601 heart failure lecture slides
TRANSCRIPT
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Heart Failure
Nicholas B. Norgard, PharmD, BCPSUniversity at Buffalo SoPPs
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Heart Failure...It is an Epidemic
Estimated that over 6 million Americans have heart failure
Estimated 500,000 new cases per year- Prevalence of HF has grown by 500% over the last 30 years
- 85% of new cases in patients over 65 years
Number one reason for hospital admissions in the US- Over 1 million hospitalizations per year with HF as primary diagnosis
High readmission rate:- 20% within one month
- 50% within six months
- 17% are readmitted two or more times
Significant cause of mortality:- Approximately 20% of HF patients die within one year of diagnosis
- 50% die within five years of diagnosis
1
Centers for Medicare and Medicaid Services. 2000 MedPAR data. DRG 127.2 Fonarow, GC. Rev Cardiovasc Med. 2002;3(suppl 4):S3.3 Krumholz HM et al. Readmission after Hospitalization for Congestive Heart Failure Among Medicare Beneficiaries. Archives of Internal Medicine, 1997 Jan 13; 157(1): 99-1-4.4 Heart Disease and Stroke Statistics 2004 Update. American Heart Association and American Stroke Association, 2004.
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Heart Failure...It is an Epidemic
Estimated that over 6 million Americans have heart failure
Estimated 500,000 new cases per year- Prevalence of HF has grown by 500% over the last 30 years
- 85% of new cases in patients over 65 years
Number one reason for hospital admissions in the US- Over 1 million hospitalizations per year with HF as primary diagnosis
High readmission rate:- 20% within one month
- 50% within six months
- 17% are readmitted two or more times
Significant cause of mortality:- Approximately 20% of HF patients die within one year of diagnosis
- 50% die within five years of diagnosis
1
Centers for Medicare and Medicaid Services. 2000 MedPAR data. DRG 127.2 Fonarow, GC. Rev Cardiovasc Med. 2002;3(suppl 4):S3.3 Krumholz HM et al. Readmission after Hospitalization for Congestive Heart Failure Among Medicare Beneficiaries. Archives of Internal Medicine, 1997 Jan 13; 157(1): 99-1-4.4 Heart Disease and Stroke Statistics 2004 Update. American Heart Association and American Stroke Association, 2004.
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Who will take care of
the heart failure patients? 2007 HF hospital discharges: 990,000
2007 HF office visits: 3,434,000 83% hospitalized once
43% hospitalized at least 4 times
2010 internists, and generalists: 50,070
2010 physicians and surgeons: 293,740
2010 cardiologists: 20,000
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Heart failure is a complex clinical syndromethat can result from any structural or
functional cardiac disorder that impairs theability of the ventricle to fill with or eject blood(i.e. heart failure is a disorder of impairedcardiac output)
Heart Failure:Definition
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HF is defined as a clinical syndrome that is characterized by specificsymptoms (dyspnea and fatigue) in the medical history and signs(edema, rales) on the physical examination.
There is no single diagnostic test for HF because it is largely a clinicaldiagnosis that is based on a careful history and physical examination.
Ways to define HF:
1. Based on ejection fraction
Heart failure with reduced ejection fraction (HFREF)
- HF symptoms and ejection fraction less than 40%
Heart failure with preserved ejection fraction (HFPEF)- HF symptoms and ejection fraction greater than 40%
2. Ischemic or nonischemic origin
CAD is most common cause of HF3. Based on HF etiology
Heart Failure:Definition
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HF is defined as a clinical syndrome that is characterized by specificsymptoms (dyspnea and fatigue) in the medical history and signs(edema, rales) on the physical examination.
There is no single diagnostic test for HF because it is largely a clinicaldiagnosis that is based on a careful history and physical examination.
Ways to define HF:
1. Based on ejection fraction
Heart failure with reduced ejection fraction (HFREF)
- HF symptoms and ejection fraction less than 40%
Heart failure with preserved ejection fraction (HFPEF)- HF symptoms and ejection fraction greater than 40%
2. Ischemic or nonischemic origin
CAD is most common cause of HF3. Based on HF etiology
Heart Failure:Definition
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HF is defined as a clinical syndrome that is characterized by specificsymptoms (dyspnea and fatigue) in the medical history and signs(edema, rales) on the physical examination.
There is no single diagnostic test for HF because it is largely a clinicaldiagnosis that is based on a careful history and physical examination.
Ways to define HF:
1. Based on ejection fraction
Heart failure with reduced ejection fraction (HFREF)
- HF symptoms and ejection fraction less than 40%
Heart failure with preserved ejection fraction (HFPEF)- HF symptoms and ejection fraction greater than 40%
2. Ischemic or nonischemic origin
CAD is most common cause of HF3. Based on HF etiology
Heart Failure:Definition
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Each time the heart beats, a volume of blood is ejected. Thisstroke volume (SV), times the number of beats per minute (heartrate, HR), equals the cardiac output (CO).
- CO = SV HR Ventricular stroke volume is the difference between the
ventricular end-diastolic volume (EDV) and the end-systolicvolume (ESV).
- SV = EDV - ESV The EDV is the filled volume of the ventricle prior to
contraction
The ESV is the residual volume of blood remaining in theventricle after ejection
Heart Failure:Hemodynamics
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CO = (EDV - ESV) HR
Heart Failure:Hemodynamics
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CO = (EDV - ESV) HR
Normal
Heart Failure:Hemodynamics
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CO = (EDV - ESV) HR
Diastolic dysfunction -Impaired ventricular fillingPrimary abnormality inheart failure with preserved
ejection fraction (HFPEF)
Heart Failure:Hemodynamics
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CO = (EDV - ESV) HR
Systolic dysfunction -Impaired ventricular emptyingAbnormality seen in heartfailure with reduced ejection
fraction (HFREF)
Heart Failure:Hemodynamics
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Heart Failure:Hemodynamics
Three determinants ofstroke volume:
1.Afterload2.Preload3.Contractility
CO = (EDV - ESV) HR
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Heart Failure Hemodynamics
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Heart Failure Hemodynamics
Contractility is difficult tomeasure but isreasonably reflected by
the ejection fraction (EF)
Ejection Fraction -percentage of end-diastolic volume ejected
with each contraction
- (stroke volumeend-diastolic volume)
Ejection Fraction cangenerally be adequatelyassessed noninvasively
with echocardiography.
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Heart Failure Hemodynamics
StrokeVolume
Afterload
Systemic Vascular resistance
Severe LVdysfunction
Mild LVdysfunction
Normal LVdysfunction
StrokeVolume
Afterload
Systemic Vascular resistance
Severe LVdysfunction
Mild LVdysfunction
Normal LVdysfunction
Afterload - the forceresisting myocardial fibercontraction at the start ofsystole
It is determined bychamber pressure,volume, and wall thicknessat the time the aortic valveopens
Clinically, systolic BPrepresents peak systolicwall stress andapproximates afterload
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Heart Failure Hemodynamics
Preload
(End-diastolic volume)
StrokeV
olume Normal
Severe LVdysfunction
Mild LVdysfunction
Preload
(End-diastolic volume)
StrokeV
olume Normal
Severe LVdysfunction
Mild LVdysfunction
Frank-Starling Mechanism -describes the relationshipbetween preload and cardiacperformance.
Strength of ventricular contractionis increased, the more theventricle is stretched prior to
contraction
If venous return is increased, theventricular end-diastolic pressureand volume of the ventricle areincreased, which stretches thesarcomeres (increases their
preload).
Increased preload increasesstroke volume (or decreasedpreload decreases stroke volume)which alters the force of cardiacmuscle contraction.
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Heart Failure Hemodynamics
Preload
(End-diastolic volume)
StrokeV
olume Normal
Severe LVdysfunction
Mild LVdysfunction
Preload
(End-diastolic volume)
StrokeV
olume Normal
Severe LVdysfunction
Mild LVdysfunction
Frank-Starling Mechanism -describes the relationshipbetween preload and cardiacperformance.
Strength of ventricular contractionis increased, the more theventricle is stretched prior to
contraction
If venous return is increased, theventricular end-diastolic pressureand volume of the ventricle areincreased, which stretches thesarcomeres (increases theirpreload
).
Increased preload increasesstroke volume (or decreasedpreload decreases stroke volume)which alters the force of cardiacmuscle contraction.
Congestion
*The heart needs a certain amount of preload (fluid from the venous system) to operate at peak efficiency. Too littlefluid and the heart fails, too much fluid and it gets backed up into the pulmonary systems (pulmonary edema).
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Heart Failure Hemodynamics
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Heart Failure...It is a Progressive Disorder
Cardiac dysfunction precipitates
changes in vascular function, blood
volume, and neurohumoral status.
Compensatory mechanisms activate:
- Tachycardia and increasedcontractility
- Frank-Starling mechanism -increase in preload results in an
increase in stroke volume
- Vasoconstriction- Ventricular hypertrophy and
remodeling
These compensatory changes over
months and years can worsen
cardiac function
Sympathetic nervous system (SNS)Renin-Angiotensin-Aldosterone system (RAAS)
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Heart Failure...It is a Progressive Disorder
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AHA HF Classification
HF A d Cl ifi i
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Stage A
Patients with risk factors for thedevelopment of structural heartdisease or overt HF
Stage BPresence of structural heartdisease (e.g. MI, LV dysfunction, or
valvular disease) without HFsymptoms
Stage CPatients with structural heartdisease and current or prior HFsymptoms
Stage DHF refractory to conventionaltreatment requiring ventricularassist device, transplantation, orpalliative care
Class INo symptoms
Class IISymptoms with moderate exertion
Class IIISymptoms with minimal exertion
Class IVSymptoms at rest
AHA Prognostic Classification NYHA Symptomatic Classification
HF Assessment and Classification
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Diagnosis of Heart Failure
Major criteria:
Paroxysmal nocturnaldyspnea
Neck vein distention Rales
Radiographic cardiomegaly(increasing heart size onchest radiography)
Acute pulmonary edema S3 gallop Increased central venous
pressure Hepatojugular reflux Weight loss >4.5 kg in 5 days
in response to treatment
Minor criteria:
Bilateral ankle edema Nocturnal cough Dyspnea on exertion Hepatomegaly
Pleural effusion Decrease in vital capacity byone third from maximumrecorded
Tachycardia (HR>120 bpm)
Minor criteria are acceptable only ifthey can not be attributed toanother medical condition (such aspulmonary hypertension, chroniclung disease, cirrhosis, or ascites).
Diagnosis of HF requires the simultaneous presence of at least 2 major
criteria or 1 major criterion in conjunction with 2 minor criteria
McKee PA, et al. N Engl J Med. 1971;285(26):1441-6
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Brain Natriuretic Peptide (BNP)
Patient presenting with Dyspnea
Physical ExamECG
Chest X-Ray
BNP < 100 pg/mlNT-proBNP < 300 pg/ml
BNP 100-500 pg/mlNT-proBNP 300-1800 pg/ml
BNP > 500 pg/mlNT-proBNP > 1800 pg/ml
Unlikely Heart FailureRule Out:
Pulmonary embolism, renalfailure, or pulmonary HTN
Likely Heart Failure
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Time progression paradigm of
chronic heart failure
T Al i h f H F il i h
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Treatment Algorithm for Heart Failure with
Reduced Ejection Fraction
McMurray J. N Engl J Med 2010;362:228-238
Diuretic + ACE inhibitor (or ARB) + Beta-blocker
Persisting signs and symptoms?
Add aldosterone antagonist;In blacks, add hydralazine-isosorbide dinitrate
Persistingsymptoms?
Considerdigoxin, LVAD,
transplant
Consider implantablecardioverter-defibrillator
No furthertreatment required
QRS >120 msec?
Consider CardiacResynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF
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Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
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Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activationRenin
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Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
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Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Elevated cardiac wall tension
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Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Elevated cardiac wall tension
Sodium and water retention
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Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervoussystem activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
Beta-blockers
Beta-blockers
VasodilatingBeta-blockers
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Effects of sympathetic activation in chronic
heart failure
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Beta Blockers
Cornerstone of pharmacotherapy for patients withheart failure
Beta-blockade is recommended in all patients withsymptomatic HF and an EF 40%
Beta-blockade improves LV function, patient well-being, reduces hospital admission for worsening HF
and increases survival
In hospitalized patients, treatment should be initiatedbefore discharge
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Poole-Wilson PA, et al. Lancet. 2003;362:7-13.
Comparison of carvedilol and metoprolol on clinical outcomes in
patients with chronic heart failure in the Carvedilol Or MetoprololEuropean Trial (COMET)
Beta Blockers
HR 0.83 [95% CI 0.74-0.93],P
= 0.0017
0 1 2 3 4 50
10
20
30
40 Metoprolol TartrateCarvedilol
Time (Years)
Mortality(%
)
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Poole-Wilson PA, et al. Lancet. 2003;362:7-13.
Comparison of carvedilol and metoprolol on clinical outcomes in
patients with chronic heart failure in the Carvedilol Or MetoprololEuropean Trial (COMET)
Beta Blockers
HR 0.83 [95% CI 0.74-0.93],P
= 0.0017
0 1 2 3 4 50
10
20
30
40 Metoprolol TartrateCarvedilol
Time (Years)
Mortality(%
)
Beta-Blockers:
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Initiate as soon as clinically stable Begin with low doses and titrate slowly
- Increase dose by 50-100% every 2 4weeks Can be done more rapidly in hospital settings
- Prior to dose titration monitor heart rate,blood pressure, pulse, fluid status andcongestion
Beta-Blockers:Dose Titration
Drug Initiation Dose Target Dose
Carvedilol 3.125 mg bid 25 mg bid
Metoprolol XL 12.5 mg daily 200 mg daily
Bisoprolol 1.25 mg daily 10 mg daily
Beta-Blockers:
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Patients with mild congestion- Maintain current beta-blocker dose
Patients with moderate to severe congestion- Increase diuretic dose, or- Reduce beta-blocker dose by 50%
In the absence of symptoms continueincreasing to maximum dose
Instruct patients that they may initially feelworse, but this should improve over time
Beta-Blockers:Dose Titration
Drug Initiation Dose Target Dose
Carvedilol 3.125 mg bid 25 mg bid
Metoprolol XL 12.5 mg daily 200 mg dailyBisoprolol 1.25 mg daily 10 mg daily
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Beta-Blockers:
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Patients with mild congestion- Maintain current beta-blocker dose
Patients with moderate to severe congestion- Increase diuretic dose, or- Reduce beta-blocker dose by 50%
In the absence of symptoms continueincreasing to maximum dose
Instruct patients that they may initially feelworse, but this should improve over time
Beta-Blockers:Dose Titration
Drug Initiation Dose Target Dose
Carvedilol 3.125 mg bid 25 mg bid
Metoprolol XL 12.5 mg daily 200 mg dailyBisoprolol 1.25 mg daily 10 mg daily
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
Beta-blockers
ACE inhibitorsBeta-blockers
Vasodilating
Beta-blockers
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Renin-Angiotensin-Aldosterone System Blockade
AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
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Renin-Angiotensin-Aldosterone System Blockade
AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
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Renin-Angiotensin-Aldosterone System Blockade
AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
ACE Inhibitor
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ACE Inhibitors
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ACE Inhibitors Cornerstone of pharmacotherapy for patients with heart failure
An ACE inhibitor is recommended in all patients with symptomatic HFand an EF 40%
Treatment with an ACE inhibitor improves LV function, patient well-being, reduces hospital admission for worsening HF and increases
survival
In hospitalized patients, treatment should be initiated beforedischarge
FIGURE 2. Angiotensin-converting enzyme inhibitor mortality trials:
CONSENUS (enalapril)31
SAVE (captopril)32
SOLVD (enalapril )33
AIRE (ramipril)34
11 0.25 0.5 0.75 1.25 1.5 1.75 2.0
31% P=.001
19% P=.19
16% P=.0014
27% P=.002
Relative risk reductions and 95% condence intervals
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Aim for dose shown to reduce mortality inclinical trials
Monitor SCr and K+ before and 1-2 weeksafter initiation and then every 3-6 months
Symptomatic hypotension and renaldysfunction typically seen in patients who arevolume depleted from diuretics
ACE Inhibitors
Drug Initiation Target Maximum
Enalapril 5 mg BID 10 mg BID 20 mg BID
Lisinopril 5 mg daily 20 mg daily 40 mg daily
Captopril 25 mg TID 50 mg TID 100 mg QID
Quinapril 10 mg BID 20 mg BID 40 mg BID
Benazepril 10 mg daily 40 mg daily 80 mg daily
Ramipril 5 mg daily 10 mg daily 20 mg daily
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
Beta-blockers
ACE inhibitors
ARBARB
Beta-blockers
VasodilatingBeta-blockers
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Renin-Angiotensin-Aldosterone System Blockade
AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
ACE Inhibitor
Non ACE pathways can takeover Angiotensin IIproduction after ACE inhibitor is initiated
Some patients have Angiotensin II levels returnto normal ~ 6months after ACE inhibitor started
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Renin-Angiotensin-Aldosterone System Blockade
AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
Non ACE pathways can takeover Angiotensin IIproduction after ACE inhibitor is initiated
Some patients have Angiotensin II levels returnto normal ~ 6months after ACE inhibitor started
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Generic/ BrandName
Initial Dose Target Dose
Losartan/
Cozaar
12.5 mg/day 50 100 mg/day
Valsartan/Diovan
80 mg/day 160 mg BID
Candasartan/Antacand
4 mg/day 32 mg/day
Angiotensin Receptor Blockers (ARBs)
An ARB is recommended in patients withHF and EF 40% who:- Are intolerant to ACE inhibitors
-Remain symptomatic despite optimal ACE inhibitortherapy (not a strong recommendation)
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Generic/ BrandName
Initial Dose Target Dose
Losartan/
Cozaar
12.5 mg/day 50 100 mg/day
Valsartan/Diovan
80 mg/day 160 mg BID
Candasartan/Antacand
4 mg/day 32 mg/day
Angiotensin Receptor Blockers (ARBs)
An ARB is recommended in patients withHF and EF 40% who:- Are intolerant to ACE inhibitors
-Remain symptomatic despite optimal ACE inhibitortherapy (not a strong recommendation)
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Generic/ BrandName
Initial Dose Target Dose
Losartan/
Cozaar
12.5 mg/day 50 100 mg/day
Valsartan/Diovan
80 mg/day 160 mg BID
Candasartan/Antacand
4 mg/day 32 mg/day
Angiotensin Receptor Blockers (ARBs)
An ARB is recommended in patients withHF and EF 40% who:- Are intolerant to ACE inhibitors
-Remain symptomatic despite optimal ACE inhibitortherapy (not a strong recommendation)
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
Beta-blockers
ACE inhibitors
ARBARB
Beta-blockers
VasodilatingBeta-blockers Diuretics
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Diuretics
Should be prescribed to all HF patients who haveevidence of fluid retention Used to restore and maintain normal volume status
(sodium and water balance)- Enhance urinary sodium excretion
- Few patients can maintain proper sodium balance without diuretics
Reduce End-Diastolic Volume (preload) Diuretics improve symptoms and exercise tolerance in
HF patients
- Produce symptomatic benefits more rapidly than any other drug for HF- Relieve pulmonary and peripheral edema within hours or days- Diuretics alone are unable to maintain the clinical stability of HF
patients for long periods of time
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Diuretics
Should be prescribed to all HF patients who haveevidence of fluid retention Used to restore and maintain normal volume status
(sodium and water balance)- Enhance urinary sodium excretion
- Few patients can maintain proper sodium balance without diuretics
Reduce End-Diastolic Volume (preload) Diuretics improve symptoms and exercise tolerance in
HF patients
- Produce symptomatic benefits more rapidly than any other drug for HF- Relieve pulmonary and peripheral edema within hours or days- Diuretics alone are unable to maintain the clinical stability of HF
patients for long periods of time
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Diuretics
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Diuretics
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Diuretics
Diuretics:
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Optimal use of diuretics is the cornerstone of a successful HF treatmentregimen
Loop diuretics > thiazides- If a patient does not response adequately to a loop, a thiazide can be added on
Initial use:- Start at low dose and titrate to effect- Once a diuretic effect is achieved with loop diuretic, increase frequency to 2-3 times a
day if necessary, rather than increasing a single dose.- Titrate dose and frequency until urine output increases and weight decreases
(generally by 0.5 to 1.0 kg daily)
- Keep output > input until patient reaches dry weight- Then back off dose and frequency to keep output = input- Have patients monitor their weight every day on the same scale
If weight goes up >2 pounds instruct patients to take an extra diuretic dose
Under diuresis can lead to fluid retention, which can increase symptomsand need for hospitalization
Over diuresis can lead to electrolyte abnormalies and volume contraction,
which can increase the risk of hypotension and renal insufficiency with
ACEIs and ARBs
Diuretics:More art than science
Diuretics:
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Optimal use of diuretics is the cornerstone of a successful HF treatmentregimen
Loop diuretics > thiazides- If a patient does not response adequately to a loop, a thiazide can be added on
Initial use:- Start at low dose and titrate to effect- Once a diuretic effect is achieved with loop diuretic, increase frequency to 2-3 times a
day if necessary, rather than increasing a single dose.- Titrate dose and frequency until urine output increases and weight decreases
(generally by 0.5 to 1.0 kg daily)
- Keep output > input until patient reaches dry weight- Then back off dose and frequency to keep output = input- Have patients monitor their weight every day on the same scale
If weight goes up >2 pounds instruct patients to take an extra diuretic dose
Under diuresis can lead to fluid retention, which can increase symptomsand need for hospitalization
Over diuresis can lead to electrolyte abnormalies and volume contraction,
which can increase the risk of hypotension and renal insufficiency with
ACEIs and ARBs
Diuretics:More art than science
Diuretics:
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Optimal use of diuretics is the cornerstone of a successful HF treatmentregimen
Loop diuretics > thiazides- If a patient does not response adequately to a loop, a thiazide can be added on
Initial use:- Start at low dose and titrate to effect- Once a diuretic effect is achieved with loop diuretic, increase frequency to 2-3 times a
day if necessary, rather than increasing a single dose.- Titrate dose and frequency until urine output increases and weight decreases
(generally by 0.5 to 1.0 kg daily)
- Keep output > input until patient reaches dry weight- Then back off dose and frequency to keep output = input- Have patients monitor their weight every day on the same scale
If weight goes up >2 pounds instruct patients to take an extra diuretic dose
Under diuresis can lead to fluid retention, which can increase symptomsand need for hospitalization
Over diuresis can lead to electrolyte abnormalies and volume contraction,
which can increase the risk of hypotension and renal insufficiency with
ACEIs and ARBs
Diuretics:More art than science
Diuretics:
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Diuretics:More art than science
Furosemide Bumetanide Torsemide Ethacrynic Acid
Equivalent intravenous doses 2040 mg 1 mg 20 mg 50 mg
Initial daily dose 2040 mg/day ortwice daily
0.51 mg/day ortwice daily
10 20 mg/day 25 50 mg/day ortwice daily
Maximum daily dosage 600 mg 10 mg 200 mg 200 mg
Duration of action 46 hours 68 hours 1216 hours 6 hours
Half-life ~ 2 hours 11 hours 24 hours 14 hours
Bioavailability 40%70% 80%95% 80%90% 100%
Intravenous-to-oral conversion 1:2 1:1 1:1 1:1
Information from Lindenfeld J, Albert NM, Boehmer JP, et al. Heart Failure Society of America 2010 comprehensive heart failure practiceguidelines. J Card Fail 2010;16:e1-e194.
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Under Diuresis
J.B. is a 54-year-old African-American man with dilated cardiomyopathy (ejectionfraction of 25% on echocardiogram 1 year ago) being seen in the clinic today with a7-day history ofdyspnea on exertion and increased lower extremity andabdominal swelling. J.B. has no other complaints. His weight has increasedfrom baseline (185 pounds) to 197 pounds. On physical examination, J.B.,routinely New York Heart Association (NYHA) class II heart failure, reports
symptoms with minimal exertion over the past week.
Vital signs are as follows blood pressure 142/62 mm Hg and heart rate 85 beats/minute. He has an S3 gallop,jugular venous distention, ascites, and 3+ pittingedema bilaterally. An electrocardiogram showed normal sinus rhythm at 80 beats/minute and QRS is 110 msec. Laboratory values include sodium 142 mmol/L,potassium 5.0 mmol/L, blood urea nitrogen 26 mg/dL, and creatinine 0.9 mg/dL.
J.B.s medical history is significant for uncontrolled hypertension and osteoarthritis.His drugs include lisinopril 20 mg/day and carvedilol 6.25 mg twice daily. J.B.recently began taking naproxen 220 mg 3 times/day for arthritic pain.
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Over Diuresis
B.S. is a 48-year-old woman, with a history of idiopathic dilatedcardiomyopathy. While in the hospital for decompensated HF,she continued her chronic drugs (lisinopril 20 mg/day andcarvedilol 25 mg twice daily) and also received intravenousfurosemide and oral metolazone. She has lost 5.5 kg since her
hospital admission 3 days ago. You notice that herblood ureanitrogen concentration has increased to 61 mg/dL andserum creatinine concentration to 2.5 mg/dL (blood ureanitrogen 23 mg/dL, and creatinine 1.1 mg/dL on admission).B.S.s vital signs are BP 86/60 mm Hg and HR 90 beats/
minute while supine. She has orthostatic BP changes withstanding.
Treatment Algorithm for Heart Failure with
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Treatment Algorithm for Heart Failure with
Reduced Ejection Fraction
McMurray J. N Engl J Med 2010;362:228-238
Diuretic + ACE inhibitor (or ARB) + Beta-blocker
Persisting signs and symptoms?
Add aldosterone antagonist;In blacks, add hydralazine-isosorbide dinitrate
Persistingsymptoms?
Considerdigoxin, LVAD,
transplant
Consider implantablecardioverter-defibrillator
No furthertreatment required
QRS >120 msec?
Consider CardiacResynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
Beta-blockers
ACE inhibitors
Aldosterone Antagonists
ARB
ARB
Beta-blockers
VasodilatingBeta-blockers Diuretics
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AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
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AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
-
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AT1 receptor
Ang I
Biologicaleffects
ACE
Non ACE pathways
Reninenzyme
Aldosterone
Retention ofwater and
salt
Ang = Angiotensin.ACE = Angiotensin converting enzyme.
AT1 = Angiotensin II Type 1.
Adapted from: Mller & Luft. Clin J Am Soc Nephrol. 2006;1:2218.
Excretionof
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
Aldosterone Antagonist
Aldosterone Antagonists:
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Aldosterone Antagonists:Spironolactone and Eplerenone
Add an aldosterone antagonist tobackground ACE inhibitor and beta-blocker therapy in patients withsymptomatic HF (NYHA class II-IV) andan EF 40%
Aldosterone antagonists arecontraindicated in patients with:
- Potassium >5.0 mEq/L- CrCl 2.5 mg/dL)
It is recommended that renal function
and potassium be measured atbaseline, then 1 week, 1 month, andevery 3 months
Zannad F, et al. N Engl J Med2011;364:1121.
Drug Initiation Target
Spironolactone 6.25 or 12.5 mg daily 25 mg daily
Eplerenone 12.5 or 25 mg daily 50 mg daily
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Pathophysiological Mechanism of Heart Failure
Heart Failure
Reduced cardiac output
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
CardiacRemodeling
Elevated cardiac wall tension
Sodium and water retention
Beta-blockers
ACE inhibitors
Aldosterone Antagonists
ARB
ARB
Beta-blockers
Hydralazine/IsosorbideVasodilating
Beta-blockers Diuretics
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Hydralazine/Isosorbide dinitrate
Isosorbide dinitrate- venodilation and reductions in preload- increase in nitric oxide bioavailability secondary to
nitric oxide donation
Hydralazine- arterial dilation to reduce afterload and increasestroke volume and cardiac output
- increase in nitric oxide bioavailability secondary toreduction in oxidative stress
Nitric oxide attenuates myocardial remodeling andmay play a protective role in heart failure.
-
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Hydralazine/Isosorbide dinitrate
Cohn JN, et al. N Engl J Med. 1991;325(5):303310.
ACE inhibitors have a reduction in mortality Hydralazine/isosorbide dinitrate improvesexercise capacity
Hydralazine/isosorbide dinitrate vs ACE inhibitors in treatment of
HF with reduced EF
Hydralazine/Isosorbide dinitrate:
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Hydralazine/Isosorbide dinitrate:A Racist Drug?
White patients:- HF more likely secondary to CAD
and the activation ofneurohormonal mechanisms
Black patients:- HF more likely secondary to
hypertension related to avascular deficiency of nitric oxide
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Hydralazine/Isosorbide dinitrate
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Hydralazine/Isosorbide dinitrate
Recommended for black HF patients whoremain symptomatic despite optimal medicaltherapy
-Not a substitute for ACE inhibitors or ARB
Appropriate as first-line therapy in all HFpatients unable to tolerate either an ACEinhibitor or ARB because of renal
insufficiency, hyperkalemia, or possiblyhypotension
Treatment Algorithm for Heart Failure with
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Treatment Algorithm for Heart Failure with
Reduced Ejection Fraction
McMurray J. N Engl J Med 2010;362:228-238
Diuretic + ACE inhibitor (or ARB) + Beta-blocker
Persisting signs and symptoms?
Add aldosterone antagonist;In blacks, add hydralazine-isosorbide dinitrate
Persistingsymptoms?
Considerdigoxin, LVAD,
transplant
Consider implantablecardioverter-defibrillator
No furthertreatment required
QRS >120 msec?
Consider CardiacResynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF
-
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yModes of Death
MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trialin congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.
12%
24%
64%
CHF
Other
SuddenDeath
n = 103
NYHA II
26%
15%
59%
CHF
Other
SuddenDeath
n = 103
NYHA III
56%
11%
33%
CHF
Other
SuddenDeath
n = 27
NYHA IV
85% of sudden death in HF from ventriculararrhythmias
Implantable Cardioverter-Defibrillator
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(ICD)
Implantable Cardioverter-Defibrillator
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(ICD)
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Treatment Algorithm for Heart Failure with
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g
Reduced Ejection Fraction
McMurray J. N Engl J Med 2010;362:228-238
Diuretic + ACE inhibitor (or ARB) + Beta-blocker
Persisting signs and symptoms?
Add aldosterone antagonist;In blacks, add hydralazine-isosorbide dinitrate
Persistingsymptoms?
Considerdigoxin, LVAD,
transplant
Consider implantablecardioverter-defibrillator
No furthertreatment required
QRS >120 msec?
Consider CardiacResynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF
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(CRT)
Cardiac remodeling can lead toconduction irregularities anddyssynchrony between the rightventricle and left ventricle
- Wide QRS (
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(CRT)
Cardiac remodeling can lead toconduction irregularities anddyssynchrony between the rightventricle and left ventricle
- Wide QRS (
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g
Reduced Ejection Fraction
McMurray J. N Engl J Med 2010;362:228-238
Diuretic + ACE inhibitor (or ARB) + Beta-blocker
Persisting signs and symptoms?
Add aldosterone antagonist;In blacks, add hydralazine-isosorbide dinitrate
Persistingsymptoms?
Considerdigoxin, LVAD,
transplant
Consider implantablecardioverter-defibrillator
No furthertreatment required
QRS >120 msec?
Consider CardiacResynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF
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gSerum concentrations
Digoxin increases parasympathetic activity- Increases cardiac index and decreases preloadwith little effect on blood pressure
Improves symptoms, exercise tolerance, andquality of life in HF patients with reduced ejectionfraction
- No mortality benefit has been shown
Serum digoxin concentrations of 0.50.8 ng/mLare associated with the best outcomes
- Levels over 1.2 ng/mL have been associatedwith an increased morbidity/mortality risk
Digoxin:S t ti
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Serum concentrations
Digoxin increases parasympathetic activity- Increases cardiac index and decreases preloadwith little effect on blood pressure
Improves symptoms, exercise tolerance, andquality of life in HF patients with reduced ejectionfraction
- No mortality benefit has been shown
Serum digoxin concentrations of 0.50.8 ng/mLare associated with the best outcomes
- Levels over 1.2 ng/mL have been associatedwith an increased morbidity/mortality risk
Digoxin
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Digoxin
Bauman JL,et al. Arch Intern Med. 2006;166(22):2539-2545
Treatment Algorithm for Heart Failure with
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Reduced Ejection Fraction
McMurray J. N Engl J Med 2010;362:228-238
Diuretic + ACE inhibitor (or ARB) + Beta-blocker
Persisting signs and symptoms?
Add aldosterone antagonist;In blacks, add hydralazine-isosorbide dinitrate
Persistingsymptoms?
Considerdigoxin, LVAD,
transplant
Consider implantablecardioverter-defibrillator
No furthertreatment required
QRS >120 msec?
Consider CardiacResynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF
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LV Assist Device
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LV Assist Device
LV Assist Device
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LV Assist Device
Heart Transplant
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Heart Transplant
Older age (usual limit 6065 y)
Active infection
Severe diabetes mellitus with other end-organ disease
Pulmonary function < 60%* predicted, or chronicbronchitis
Serum creatinine > 2 mg/dL or clearance < 40 mL/min*
Bilirubin > 2.5 mg/dL, transaminases 2 normal*
PAS > 60 mm Hg, TPG > 15 mm Hg*
High risk of life-threatening noncompliance
Specific contraindications tocardiac transplantation
Heart Transplant
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Heart Transplant
Older age (usual limit 6065 y)
Active infection
Severe diabetes mellitus with other end-organ disease
Pulmonary function < 60%* predicted, or chronicbronchitis
Serum creatinine > 2 mg/dL or clearance < 40 mL/min*
Bilirubin > 2.5 mg/dL, transaminases 2 normal*
PAS > 60 mm Hg, TPG > 15 mm Hg*
High risk of life-threatening noncompliance
Specific contraindications tocardiac transplantation
Heart Transplant
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Heart Transplant
Older age (usual limit 6065 y)
Active infection
Severe diabetes mellitus with other end-organ disease
Pulmonary function < 60%* predicted, or chronicbronchitis
Serum creatinine > 2 mg/dL or clearance < 40 mL/min*
Bilirubin > 2.5 mg/dL, transaminases 2 normal*
PAS > 60 mm Hg, TPG > 15 mm Hg*
High risk of life-threatening noncompliance
Specific contraindications tocardiac transplantation
Heart Transplant
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Heart Transplant
Older age (usual limit 6065 y)
Active infection
Severe diabetes mellitus with other end-organ disease
Pulmonary function < 60%* predicted, or chronicbronchitis
Serum creatinine > 2 mg/dL or clearance < 40 mL/min*
Bilirubin > 2.5 mg/dL, transaminases 2 normal*
PAS > 60 mm Hg, TPG > 15 mm Hg*
High risk of life-threatening noncompliance
Specific contraindications tocardiac transplantation
Drugs to avoid in patients with HF withReduced Ejection Fraction
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Reduced Ejection Fraction
Drugs known to adversely affect the clinical statusof patients with current or prior symptoms of HF andreduced LVEF should be avoided or withdrawnwhenever possible
- NSAIDs- Antiarrhythmics: Class Ia, Class Ic, dronedarone
- Non-dihydropyridine calcium channel blockers
- Thiazolidinediones
Treatment for Heart Failure with
Reduced Ejection Fraction
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Reduced Ejection Fraction
Hormonal therapies other than to repletedeficiencies are not recommended and may beharmful to patients with current or priorsymptoms of HF and reduced LVEF.
Use of nutritional supplements as treatment forHF is not indicated in patients with current or
prior symptoms of HF and reduced LVEF.
Heart Failure with Preserved
Ejection Fraction (HFPEF)
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Ejection Fraction (HFPEF)
Heart Failure with Preserved
Ejection Fraction (HFPEF)
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20 to 50 percent of patients with HF have apreserved ejection fraction
Patients with HFPEF:- Typically older and more likely to be women- Higher prevalence of hypertension, obesity,
renal failure, anemia, and atrial fibrillation
No evidence- based treatment for patients withHFPEF
Ejection Fraction (HFPEF)
Heart Failure with Preserved
Ejection Fraction (HFPEF)
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Ejection Fraction (HFPEF)
Treat hypertension according to publishedguidelines
- Be wary of compelling indications such asdiabetes and left ventricular hypertrophy
Treat CAD according to publishedguidelines Control ventricular rate in patients with
HFPEF and atrial fibrillation Use diuretics to control pulmonary
congestion and peripheral edema
Acute heart failure syndromes (AHFS)
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New-onset, gradual, or rapidly worsening HF signs andsymptoms that require urgent therapy.
Acute heart failure syndromes (AHFS)
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Predictors of Mortality Based on
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Analysis of ADHERE DatabaseThree variables are the strongest predictors of mortality inhospitalized acute decompensated HF patients:
Patients with all three characteristics had an in-hospitalmortality of 21.9 percent compared to 2.1 percent inpatients with none.
BUN > 43 mg/dL
Systolic blood pressure < 115 mmHg
Serum creatinine > 2.75 mg/dL
Fonarow GC et al. JAMA 2005;293:572-80
Acute heart failure syndromes (AHFS)
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Medical management of AHFS is based on
precipitating factors and clinical presentationIdentification of potential precipitating factors for acuteHF is critical to guide therapy:
acute coronary syndromes/coronary ischemia severe hypertension atrial and ventricular arrhythmias infections
pulmonary emboli
renal failure medical or dietary noncompliance
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In patients experiencing a HF exacerbation requiring
hospitalization:
- Treatment with ACE inhibitors or ARBs should be continued inmost patients in the absence of hemodynamic instability
- Continuation of beta blocker therapy is recommended in mostpatients, unless they develop cardiogenic shock, refractoryvolume overload, or symptomatic bradycardia.
Temporary dose reduction may be considered Avoid abrupt discontinuation
Reinstate or gradually increase prior to discharge Titrate dose to previously tolerated dose as soon as possible
In hospitalized HF patients not treated with ACE inhibitors orARBs and beta-blocker therapy, initiation of these therapies isrecommended in stable patients prior to hospital discharge.
Acute heart failure syndromes (AHFS)
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Medical management of AHFS is based on precipitating
factors and clinical presentation
Warm & Dry Warm & Wet
Cold & WetCold & Dry
Congestion at Rest?
Low Perfusionat Rest?
I II
III IV
No
No Yes
Yes
CardiacIndex
2.2l/min/m2
PCWP
18 mmHg
Evidence of low perfusion:
Cool extremities
Narrow pulse pressure Low serum sodium Renal dysfunction Hypotension with ACE inhibitorAltered Mental Status
Signs/symptoms of congestion:
Orthopnea/PND JVDAscites Edema Rales
Congestion
Hypoperfusion
Hemodynamic Monitoring
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Hemodynamic Monitoring Swan-Ganz Catheter Used when congestion and perfusion cannot be
determined from clinical assessment or whensymptoms persist despite empiric adjustment ofstandard therapies
Allows measurement:- Right atrial pressure- Right ventricular pressure- Pulmonary artery capillary pressure ("wedge"
pressure)
- Cardiac index- Systemic vascular resistance
Acute Heart Failure Syndromes (AHFS)
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PCWP18 mmHg
Warm & Dry Warm & Wet
Cold & WetCold & Dry
I II
III IV
CardiacIndex
2.2l/min/m2
Normal
Mild to ModerateLV Dysfunction
SevereLV Dysfunction
Warm and Wet
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Warm and Wet
T.J. is a 65-year-old man who came into the hospital withincreasing dyspnea at rest. A physical examination revealsrales throughout his lung fields. His chest X-Ray showedpulmonary congestion. He was diagnosed with AHFS.Echocardiography revealed an LVEF of 45%. He has a
history of hypertension, hyperlipidemia, and coronary arterydisease with a three-vessel coronary artery bypass graft 2years ago. T.J.s vital signs are BP 182/81 mm Hg and HR 85beats/minute.
Warm and Wet
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Warm and Wet
T.J. is a 65-year-old man who came into the hospital withincreasing dyspnea at rest. A physical examination revealsrales throughout his lung fields. His chest X-Ray showedpulmonary congestion. He was diagnosed with AHFS.Echocardiography revealed an LVEF of 45%. He has a
history of hypertension, hyperlipidemia, and coronary arterydisease with a three-vessel coronary artery bypass graft 2years ago. T.J.s vital signs are BP 182/81 mm Hg and HR 85beats/minute.
A Swan-Ganz catheter reveals a cardiac index of 2.6 L/minute/m2 and pulmonary capillary wedge pressure (PCWP)of 25 mm Hg.
Acute Heart Failure Syndromes (AHFS)Warm & Wet
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PCWP
18 mmHg
Warm & Dry Warm & Wet
Cold & WetCold & Dry
I II
III IV
Cardiac
Index2.2
l/min/m2
Use drugs that reducepreload (PCWP)
Diuretics
Vasodilators
Warm & Wet
Warm & Wet
Acute Heart Failure Syndromes (AHFS)Warm & Wet
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Warm & Wet
Assess voluConsider ca
diuresis vsif hypovol
HF progress
Fluid overload:Orthopnea/PND JVD
RalesDOE/SOBS3 or S4HJR NT-proBNPWeight gainEdemaPulmonary edema
Assess signsand symptoms
Mild volume overload
IV diureticsIV furosemide: On oral furosemide as
outpatient: give 12 xpatient home dose as IVbolus (max = 180 mg)
No oral furosemide asoutpatient: give 20 40mg as IV bolus
Moderate to severevolume overload andSBP > 90 mm Hg
FatiguePre-renal azotemiaPoor response to IV
diuretic Oxygen requirementRequiring CPAP or BiPAP
If uncertain ofhemodynamic status,consider pulmonaryartery catheter
Assess response to initial diureticIf UOP < 250500 mL aer 2 hours:Double previous IV bolus dose
OR
Double previous IV bolus dosefollowed by continuous infusion
OR
Double previous IV bolus dose + POmetolazone or IV chlorothiazide
Reassess UOP as above, and ifineective, consider moderate tosevere volume overload or low CO
IV diuretics +IV vasodilators
IV diuretic: continue diuretic
regimen titrated to UOP goalsIV vasodilatorNitroglycerinNitroprussideNesiritideUltraltration is also an option
for uid removal
IV loop diuretics should begin in the emergencydepartment or outpatient clinic without delay
- Initial IV dose should equal or exceed chronicoral daily dose
Urine output, daily weight, and signs and symptomsof congestion should be serially assessed, and
diuretic dose should be titrated accordingly torelieve symptoms and to reduce fluid excess
When diuresis is inadequate to relieve congestionthe diuretic regimen should be intensified usingeither:
- higher and more frequent doses of loop diuretics;- addition of a second diuretic (metolazone or IV
chlorthiazide); or
- continuous infusion of a loop diuretic.
Acute Heart Failure Syndromes (AHFS)Warm & Wet
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Warm & Wet
Assess voluConsider ca
diuresis vsif hypovol
HF progress
Fluid overload:Orthopnea/PND JVD
RalesDOE/SOBS3 or S4HJR NT-proBNPWeight gainEdemaPulmonary edema
Assess signsand symptoms
Mild volume overload
IV diureticsIV furosemide: On oral furosemide as
outpatient: give 12 xpatient home dose as IVbolus (max = 180 mg)
No oral furosemide asoutpatient: give 20 40mg as IV bolus
Moderate to severevolume overload andSBP > 90 mm Hg
FatiguePre-renal azotemiaPoor response to IV
diuretic Oxygen requirementRequiring CPAP or BiPAP
If uncertain ofhemodynamic status,consider pulmonaryartery catheter
Assess response to initial diureticIf UOP < 250500 mL aer 2 hours:Double previous IV bolus dose
OR
Double previous IV bolus dosefollowed by continuous infusion
OR
Double previous IV bolus dose + POmetolazone or IV chlorothiazide
Reassess UOP as above, and ifineective, consider moderate tosevere volume overload or low CO
IV diuretics +IV vasodilators
IV diuretic: continue diuretic
regimen titrated to UOP goalsIV vasodilatorNitroglycerinNitroprussideNesiritideUltraltration is also an option
for uid removal
In patients with evidence ofseverely symptomatic fluidoverload in the absence ofsystemic hypotension, IV
vasodilators can be beneficialwhen added to diuretics and/orin those who do not respond todiuretics alone:
-Nitroglycerin
- Nitroprusside- Nesiritide?
Acute Heart Failure Syndromes (AHFS)Warm & Wet
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Warm & Wet
Assess voluConsider ca
diuresis vsif hypovol
HF progress
Fluid overload:Orthopnea/PND JVD
RalesDOE/SOBS3 or S4HJR NT-proBNPWeight gainEdemaPulmonary edema
Assess signsand symptoms
Mild volume overload
IV diureticsIV furosemide: On oral furosemide as
outpatient: give 12 xpatient home dose as IVbolus (max = 180 mg)
No oral furosemide asoutpatient: give 20 40mg as IV bolus
Moderate to severevolume overload andSBP > 90 mm Hg
FatiguePre-renal azotemiaPoor response to IV
diuretic Oxygen requirementRequiring CPAP or BiPAP
If uncertain ofhemodynamic status,consider pulmonaryartery catheter
Assess response to initial diureticIf UOP < 250500 mL aer 2 hours:Double previous IV bolus dose
OR
Double previous IV bolus dosefollowed by continuous infusion
OR
Double previous IV bolus dose + POmetolazone or IV chlorothiazide
Reassess UOP as above, and ifineective, consider moderate tosevere volume overload or low CO
IV diuretics +IV vasodilators
IV diuretic: continue diuretic
regimen titrated to UOP goalsIV vasodilatorNitroglycerinNitroprussideNesiritideUltraltration is also an option
for uid removal
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Warm & Wet
Assess voluConsider ca
diuresis vsif hypovol
HF progress
Fluid overload:Orthopnea/PND JVD
RalesDOE/SOBS3 or S4HJR NT-proBNPWeight gainEdemaPulmonary edema
Assess signsand symptoms
Mild volume overload
IV diureticsIV furosemide: On oral furosemide as
outpatient: give 12 xpatient home dose as IVbolus (max = 180 mg)
No oral furosemide asoutpatient: give 20 40mg as IV bolus
Moderate to severevolume overload andSBP > 90 mm Hg
FatiguePre-renal azotemiaPoor response to IV
diuretic Oxygen requirementRequiring CPAP or BiPAP
If uncertain ofhemodynamic status,consider pulmonaryartery catheter
Assess response to initial diureticIf UOP < 250500 mL aer 2 hours:Double previous IV bolus dose
OR
Double previous IV bolus dosefollowed by continuous infusion
OR
Double previous IV bolus dose + POmetolazone or IV chlorothiazide
Reassess UOP as above, and ifineective, consider moderate tosevere volume overload or low CO
IV diuretics +IV vasodilators
IV diuretic: continue diuretic
regimen titrated to UOP goalsIV vasodilatorNitroglycerinNitroprussideNesiritideUltraltration is also an option
for uid removal
In patients with evidence ofseverely symptomatic fluidoverload in the absence ofsystemic hypotension, IV
vasodilators can be beneficialwhen added to diuretics and/orin those who do not respond todiuretics alone:
-Nitroglycerin
- Nitroprusside- Nesiritide?
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Effect of HF treatment should be monitored withcareful measurement of:- fluid intake and output- vital signs
-body weight, determined at the same time each day
- clinical signs (supine and standing) and symptoms of systemicperfusion and congestion
Daily serum electrolytes, blood urea nitrogen, andserum creatinine concentrations should be measured
during the use of IV diuretics or active titration of HFmedications.
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Cold and Wet
K.L., a 58-year-old man with a 3-year history of non-ischemiccardiomyopathy, is admitted to the hospital forsevereshortness of breath and altered mental status. He hasgained 11 kg over the past 2 weeks (now weighs 120 kg) andhas had decreased urine output despite increasing his
diuretic dose. A physical examination reveals ralesthroughout his lung fields. K.L.s blood pressure (BP) is 84/63mm Hg.
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Cold and Wet
K.L., a 58-year-old man with a 3-year history of non-ischemiccardiomyopathy, is admitted to the hospital forsevereshortness of breath and altered mental status. He hasgained 11 kg over the past 2 weeks (now weighs 120 kg) andhas had decreased urine output despite increasing his
diuretic dose. A physical examination reveals ralesthroughout his lung fields. K.L.s blood pressure (BP) is 84/63mm Hg.
A Swan-Ganz catheter reveals a cardiac index of 1.6 L/minute/m2 and pulmonary capillary wedge pressure (PCWP)of 25 mm Hg.
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PCWP
18 mmHg
Warm & Dry Warm & Wet
Cold & WetCold & Dry
I II
III IV
Cardiac
Index2.2
l/min/m2
Use combination of:
Inotropes (I) Diuretics (D)
Vasodilators (V)
I
D
V
I+V
D+V+I
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Intravenous inotropic drugs are reasonablefor patients presenting with (1) severesystolic dysfunction, (2) symptomatichypotension or (3) inability to maintain
systemic perfusion and preserve end-organperformance
- Dobutamine
-Milrinone
- Dopamine
Assess volume statusConsider careful IV
diuresis vs. uid bolusif hypovolemic
vs
HF progression to low CO
Assess blood pressure
NoYes
On -blocker chronically
nsms
SBP > 90 mm Hg SBP < 90 mm Hg
Low CO:Narrow pulse pressurePre-renal azotemia
Altered mental status
UOPPoor response to IVdiureticCool extremitiesPulsus alternans
DobutamineMilrinone
Continued signs/symptoms of low CO
c status,onary
r
Very low COConsider pulmonary artery catheterConsider vasodilators aer known
hemodynamic parametersConsider dopamine if severe
hypotension or cardiogenic shock
e diuretic
UOP goals
an option
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Assess volume statusConsider careful IV
diuresis vs. uid bolusif hypovolemic
vs
HF progression to low CO
Assess blood pressure
NoYes
On -blocker chronically
nsms
SBP > 90 mm Hg SBP < 90 mm Hg
Low CO:Narrow pulse pressurePre-renal azotemia
Altered mental status
UOPPoor response to IVdiureticCool extremitiesPulsus alternans
DobutamineMilrinone
Continued signs/symptoms of low CO
c status,onary
r
Very low COConsider pulmonary artery catheterConsider vasodilators aer known
hemodynamic parametersConsider dopamine if severe
hypotension or cardiogenic shock
e diuretic
UOP goals
an option
Drug Dose 1 1 2 DA
0.5 - 3 mcg/kg/min 0 0 0 +++++
Dopamine 4 - 10 mcg/kg/min ++ ++++ ++ +++++
> 10 mcg/kg/min ++++ ++++ ++ +++++
2.0 - 10 mcg/kg/min + +++++ +++ 0
10 - 20 mcg/kg/min ++ +++++ +++ 0
Milrinone0.375 to 0.75 mcg/kg/min
0 0 0 0
Milrinone is a selective phosphodiesterase-3 inhibitor (PDE3) thatincreases the level of cAMP by inhibiting its breakdown within the cell
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Assess volume statusConsider careful IV
diuresis vs. uid bolusif hypovolemic
vs
HF progression to low CO
Assess blood pressure
NoYes
On -blocker chronically
nsms
SBP > 90 mm Hg SBP < 90 mm Hg
Low CO:Narrow pulse pressurePre-renal azotemia
Altered mental status
UOPPoor response to IVdiureticCool extremitiesPulsus alternans
DobutamineMilrinone
Continued signs/symptoms of low CO
c status,onary
r
Very low COConsider pulmonary artery catheterConsider vasodilators aer known
hemodynamic parametersConsider dopamine if severe
hypotension or cardiogenic shock
e diuretic
UOP goals
an option
Dobutamine and milrinone are preferable over dopaminewhen blood pressure is adequate
-
Dobutamine reduces the systemic vascular resistanceand may not increase oxygen demands as much asdopamine, and is preferable when systolic bloodpressure >80 mmHg
-Milrinone is not dependent upon adrenergic receptoractivity and therefore, is preferable for patients on beta-blockers. Causes greatest reduction preload, thus may
be least likely to increase myocardial oxygen demand
Selection of an inotrope
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Assess volume statusConsider careful IV
diuresis vs. uid bolusif hypovolemic
vs
HF progression to low CO
Assess blood pressure
NoYes
On -blocker chronically
nsms
SBP > 90 mm Hg SBP < 90 mm Hg
Low CO:Narrow pulse pressurePre-renal azotemia
Altered mental status
UOPPoor response to IVdiureticCool extremitiesPulsus alternans
DobutamineMilrinone
Continued signs/symptoms of low CO
c status,onary
r
Very low COConsider pulmonary artery catheterConsider vasodilators aer known
hemodynamic parametersConsider dopamine if severe
hypotension or cardiogenic shock
e diuretic
UOP goals
an option
Dopamine should be initiated first for severehypotension
- Patients may not tolerate the vasodilating effects ofdobutamine or milrinone at low blood pressures
If dopamine at doses of 20 mcg/kg/min does not achievea MAP of 60-65 mm Hg, then norepinephrine can beadded
Selection of an inotrope
Hospital to Home
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p
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Questions?Contact me:
Nicholas B. Norgard, Pharm.D. BCPS
University at Buffalo School of Pharmacy &Pharmaceutical SciencesCenter of Excellence B3-322
Office: 716-645-4779