PHM 601 Heart Failure Lecture Slides

Heart Failure
Nicholas B. Norgard, PharmD, BCPS

University at Buffalo SoPPs
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.
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.
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
Heart failure is a complex clinical syndrome
that can result from any structural or
functional cardiac disorder that impairs the
ability of the ventricle to fill with or eject blood
(i.e. heart failure is a disorder of impaired
cardiac output)
Heart Failure:
Denition
HF is defined as a clinical syndrome that is characterized by specific

symptoms (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 clinical

diagnosis 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 HF

3. Based on HF etiology
Heart Failure:
Denition


Ways to define HF:


Heart Failure:
Denition


Ways to define HF:


Heart Failure:
Denition
Each time the heart beats, a volume of blood is ejected. This

stroke volume (SV), times the number of beats per minute (heart
rate, 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-systolic
volume (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 the

ventricle after ejection
Heart Failure:
Hemodynamics
CO = (EDV - ESV) HR
Heart Failure:
Hemodynamics
CO = (EDV - ESV) HR
Normal
Heart Failure:
Hemodynamics
CO = (EDV - ESV) HR
Diastolic dysfunction -
Impaired ventricular filling
Primary abnormality in
heart failure with preserved
ejection fraction (HFPEF)
Heart Failure:
Hemodynamics
CO = (EDV - ESV) HR
Systolic dysfunction -
Impaired ventricular emptying
Abnormality seen in heart

failure with reduced ejection
fraction (HFREF)
Heart Failure:
Hemodynamics
Heart Failure:
Hemodynamics
Three determinants of
stroke volume:
1.Afterload
2.Preload
3.Contractility
CO = (EDV - ESV) HR
Heart Failure Hemodynamics
Contractility is difficult to
measure but is
reasonably reflected by
the ejection fraction (EF)
Ejection Fraction -
percentage of end-
diastolic volume ejected
with each contraction
-
(stroke volumeend-
diastolic volume)
Ejection Fraction can

generally be adequately
assessed noninvasively
with echocardiography.
S
t
r
o
k
e

V
o
l
u
m
e
Afterload
Systemic Vascular resistance
Severe LV
dysfunction
Mild LV
dysfunction
Normal LV
dysfunction
S
t
r
o
k
e

V
o
l
u
m
e
Afterload
Systemic Vascular resistance
Severe LV
dysfunction
Mild LV
dysfunction
Normal LV
dysfunction
Afterload - the force

resisting myocardial fiber
contraction at the start of
systole
It is determined by
chamber pressure,
volume, and wall thickness
at the time the aortic valve
opens
Clinically, systolic BP
represents peak systolic
wall stress and
approximates afterload
Preload
(End-diastolic volume)
S
t
r
o
k
e

V
o
l
u
m
e
Normal
Severe LV
dysfunction
Mild LV
dysfunction
Preload
S
t
r
o
k
e

V
o
l
u
m
e
Normal
Severe LV
dysfunction
Mild LV
dysfunction
Frank-Starling Mechanism -
describes the relationship
between preload and cardiac
performance.
Strength of ventricular contraction

is increased, the more the
ventricle is stretched prior to
contraction
If venous return is increased, the

ventricular end-diastolic pressure
and volume of the ventricle are
increased, which stretches the
sarcomeres (increases their
preload).
Increased preload increases

stroke volume (or decreased
preload decreases stroke volume)
which alters the force of cardiac
muscle contraction.
Preload
S
t
r
o
k
e

V
o
l
u
m
e
Normal
Severe LV
dysfunction
Mild LV
dysfunction
Preload
S
t
r
o
k
e

V
o
l
u
m
e
Normal
Severe LV
dysfunction
Mild LV
dysfunction
Frank-Starling Mechanism -
describes the relationship
between preload and cardiac
performance.
Strength of ventricular contraction

is increased, the more the
ventricle is stretched prior to
contraction
If venous return is increased, the

ventricular end-diastolic pressure
and volume of the ventricle are
increased, which stretches the
sarcomeres (increases their
preload).
Increased preload increases

stroke volume (or decreased
preload decreases stroke volume)
which alters the force of cardiac
muscle contraction.
Congestion
*The heart needs a certain amount of preload (fluid from the venous system) to operate at peak efficiency. Too little
fluid and the heart fails, too much fluid and it gets backed up into the pulmonary systems (pulmonary edema).
Heart Failure...
It is a Progressive Disorder
Cardiac dysfunction precipitates

changes in vascular function, blood
volume, and neurohumoral status.
Compensatory mechanisms activate:

-
Tachycardia and increased
contractility
-
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)
Heart Failure...
It is a Progressive Disorder
AHA HF Classication
Stage A
Patients with risk factors for the
development of structural heart
disease or overt HF
Stage B
Presence of structural heart
disease (e.g. MI, LV dysfunction, or
valvular disease) without HF
symptoms
Stage C
Patients with structural heart
disease and current or prior HF
symptoms
Stage D
HF refractory to conventional
treatment requiring ventricular
assist device, transplantation, or
palliative care
Class I
No symptoms
Class II
Symptoms with moderate exertion
Class III
Symptoms with minimal exertion
Class IV
Symptoms at rest
AHA Prognostic Classification NYHA Symptomatic Classification
HF Assessment and Classication
Stage A
Patients with risk factors for the
development of structural heart
disease or overt HF
Stage B
Presence of structural heart
disease (e.g. MI, LV dysfunction, or
valvular disease) without HF
symptoms
Stage C
Patients with structural heart
disease and current or prior HF
symptoms
Stage D
HF refractory to conventional
treatment requiring ventricular
assist device, transplantation, or
palliative care
Class I
No symptoms
Class II
Symptoms with moderate exertion
Class III
Symptoms with minimal exertion
Class IV
Symptoms at rest
AHA Prognostic Classification NYHA Symptomatic Classification
HF Assessment and Classication
Diagnosis of Heart Failure
Major criteria:
Paroxysmal nocturnal
dyspnea
Neck vein distention
Rales
Radiographic cardiomegaly
(increasing heart size on
chest 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 by

one third from maximum
recorded
Tachycardia (HR>120 bpm)

Minor criteria are acceptable only if
they can not be attributed to
another medical condition (such as
pulmonary hypertension, chronic
lung 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
Brain Natriuretic Peptide (BNP)
Patient presenting with Dyspnea
Physical Exam
ECG
Chest X-Ray
BNP < 100 pg/ml
NT-proBNP < 300 pg/ml
BNP 100-500 pg/ml
NT-proBNP 300-1800 pg/ml
BNP > 500 pg/ml
NT-proBNP > 1800 pg/ml
Unlikely Heart Failure
Rule Out:
Pulmonary embolism, renal
failure, or pulmonary HTN
Likely Heart Failure
Time progression paradigm of
chronic heart failure
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
Persisting
symptoms?
Consider
digoxin, LVAD,
transplant
Consider implantable
cardioverter-
defibrillator
No further
treatment required
QRS >120 msec?
Consider Cardiac
Resynchronization
Therapy Defibrillator
Yes
Yes
Yes No
LVEF <35%
Yes
No
No
No
Pathophysiological Mechanism of Heart Failure
Reduced cardiac output
Sympathetic nervous
system activation
Renin
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Elevated cardiac wall tension
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Sodium and water retention
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Beta-blockers
Beta-blockers
Vasodilating
Beta-blockers
Effects of sympathetic activation in chronic
heart failure
Beta Blockers
Cornerstone of pharmacotherapy for patients with

heart failure
Beta-blockade is recommended in all patients with

symptomatic 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 initiated

before discharge
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 Metoprolol
European Trial (COMET)
Beta Blockers
HR 0.83 [95% CI 0.74-0.93], P= 0.0017
0 1 2 3 4 5
0
10
20
30
40
Metoprolol Tartrate
Carvedilol
Time (Years)
M
o
r
t
a
l
i
t
y

(
%
)
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 Metoprolol
European Trial (COMET)
Beta Blockers
HR 0.83 [95% CI 0.74-0.93], P= 0.0017
0 1 2 3 4 5
0
10
20
30
40
Metoprolol Tartrate
Carvedilol
Time (Years)
M
o
r
t
a
l
i
t
y

(
%
)
Initiate as soon as clinically stable
Begin with low doses and titrate slowly

-
Increase dose by 50-100% every 2 4
weeks
Can be done more rapidly in hospital settings

-
Prior to dose titration monitor heart rate,
blood pressure, pulse, fluid status and
congestion
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
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 continue

increasing to maximum dose
Instruct patients that they may initially feel

worse, but this should improve over time
Beta-Blockers:
Dose Titration

-

-
-


Beta-Blockers:
Dose Titration

-

-
-


Beta-Blockers:
Dose Titration
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Beta-blockers
ACE inhibitors
Beta-blockers
Vasodilating
Beta-blockers
Renin-Angiotensin-Aldosterone System Blockade
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water 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.
Excretion
of
potassium
Ang II
Angiotensinogen
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ACE Inhibitors
ACE Inhibitors
Cornerstone of pharmacotherapy for patients with heart failure
An ACE inhibitor is recommended in all patients with symptomatic HF

and 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 before

discharge
DIAGNOSIS AND MANAGEMENT OF CHRONIC HEART FAILURE
Mayo Clin Proc. February 2010,85(2).180-195 doi.10.4065/mcp.2009.0494 www.mayoclinicproceedings.com 183
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings a .
CLINICAL PEARLS IN SUCCESSFUL
HEART FAILURE THERAPY
BEHAVIORAL AND LIFESTYLE MODIFICATIONS ARE ESSENTIAL TO
ENSURING SUCCESS OF HEART FAILURE PHARMACOTHERAPY
Before initiation of pharmacotherapy, patients must be coun-
seled regarding the importance of dietary discretion, and nu-
tritional consultation should be provided. Strict adherence
should be emphasized, and the importance of daily weight
measurements addressed. Patients should be provided with
instructions regarding diuretic dosing adjustments for sud-
den changes in weight.
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND -BLOCKERS
FORM THE CORNERSTONE OF CHF PHARMACOTHERAPY
Figures 2
31-34
and 3
35-37
summarize the results of the ef-
fects of treatment with angiotensin-converting enzyme in-
hibitors (ACEIs) and -blockers, respectively, on all-cause
mortality. On a cellular level, ACEIs slow the progression
of cardiovascular disease by multiple pleiotropic effects,
including improved endothelial function; antiproliferative
effects on smooth muscle cells, neutrophils, and mono-
cytes; and antithrombotic effects.
38
Meta-analyses suggest
a 23% reduction in mortality and a 35% reduction in the
combination end point of mortality and hospitalizations for
heart failure in patients treated with ACEIs.
39
-Blockers
up-regulate -1 receptor density, blunt norepinephrine and
renin production, and mitigate production of deleterious cy-
tokines, including tumor necrosis factor .
40
Large-scale
clinical trials demonstrated a 35% reduction in mortality in
patients treated with -blockers on top of the benet pro-
vided by ACEIs alone.
35,36
Increased experience with both
agents in a broad range of patients with heart failure has
shown the safety of ACEIs in treating patients with mild
renal insufciency and the tolerability of -blockers in pa-
tients with moderately controlled diabetes, asthma, and ob-
structive lung disease. The benets of -blockers and ACEIs
extend to patients with class IV heart failure.
37
Patients with
advanced disease may not be able to tolerate escalating dos-
es of -blockers, and the need to withdraw or reduce doses
of established medications due to dizziness or hypotension
may be an ominous sign of worsening heart failure.
WHEREAS THE BENEFITS OF ACEIS APPEAR TO BE CLASS
SPECIFIC, -BLOCKER USE SHOULD BE RELEGATED TO
CLINICAL TRIALS
Although there was initial optimism surrounding the use of
tissue ACEIs vs non-tissue ACEIs, there appears to be no
signicant difference in outcomes between agents, and the
benets appear to be a class effect.
41
Conversely, the ben-
ecial effects of -blockers are thought to be limited to
specic drugs. -Blockers with intrinsic sympathomimetic
activity (xamoterol) and other agents, including bucindolol,
have not demonstrated a survival benet.
42,43
On the basis of
these studies, we recommend that -blocker use be restricted
to carvedilol, bisoprolol, and metoprolol succinate, agents
proven to improve survival in clinical trials.
IN PATIENTS WITH NEWLY DIAGNOSED CHF, IT IS SAFE TO USE
EITHER A -BLOCKER OR AN ACEI AS FIRST-LINE THERAPY
The long-established paradigm had typically been to initi-
ate ACEI therapy before -blocker therapy, primarily be-
cause -blocker studies were performed with background
ACEI therapy. Which of these agents was used as initial
TABLE 2. Targets of Medical Therapy in Patients
With Heart Failure
Target of therapy Therapeutic agent Safety Survival
Sympathetic nervous
system -Blockers Y Y
RAAS ACEIs Y Y
RAAS ARBs Y Y
RAAS/cellular turnover Aldosterone antagonists Y Y
Baroreceptor
dysfunction Digoxin Y N
Vasopressin antagonisn Tolvaptan Y N
Altered systemic
vascular resistance Hydralazine and nitrates Y Y
Altered systemic Dihydropyridine calcium Y N
vascular resistance channel blockers
Altered systemic Nondihydropyridine N N
vascular resistance calcium channel
blockers
Congestion and altered
cardiorenal dynamics Diuretic agents Y N
Coagulopathy Warfarin Y N
Inammation Statins Y N
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II
receptor blocker; RAAS = renin-angiotensin-aldosterone system.
FIGURE 2. Angiotensin-converting enzyme inhibitor mortality trials:
all-cause mortality results. AIRE = Acute Infarction Ramipril Efcacy;
CONSENSUS = Cooperative North Scandinavian Enalapril Survival
Study; SAVE = Survival and Ventricular Enlargement; SOLVD = Stud-
ies of Left Ventricular Dysfunction.
CONSENUS (enalapril)
31

SAVE (captopril)
32
SOLVD (enalapril)
33
AIRE (ramipril)
34
1 1 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
Aim for dose shown to reduce mortality in

clinical trials
Monitor SCr and K+ before and 1-2 weeks

after initiation and then every 3-6 months
Symptomatic hypotension and renal

dysfunction typically seen in patients who are
volume 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
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Beta-blockers
ACE inhibitors
ARB
ARB
Beta-blockers
Vasodilating
Beta-blockers
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
ACE Inhibitor
Non ACE pathways can takeover Angiotensin II
production after ACE inhibitor is initiated
Some patients have Angiotensin II levels return
to normal ~ 6months after ACE inhibitor started
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
Non ACE pathways can takeover Angiotensin II
production after ACE inhibitor is initiated
Some patients have Angiotensin II levels return
to normal ~ 6months after ACE inhibitor started
Generic/ Brand
Name
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 with

HF and EF 40% who:
-
Are intolerant to ACE inhibitors
-
Remain symptomatic despite optimal ACE inhibitor
therapy (not a strong recommendation)
Generic/ Brand
Name
Losartan/
Cozaar
Valsartan/
Diovan
Candasartan/
Antacand
4 mg/day 32 mg/day

HF and EF 40% who:
-
-
Generic/ Brand
Name
Losartan/
Cozaar
Valsartan/
Diovan
Candasartan/
Antacand
4 mg/day 32 mg/day

HF and EF 40% who:
-
-
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Beta-blockers
ACE inhibitors
ARB
ARB
Beta-blockers
Vasodilating
Beta-blockers Diuretics
Diuretics
Should be prescribed to all HF patients who have

evidence 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
Diuretics
Should be prescribed to all HF patients who have

evidence 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
Diuretics
Diuretics
Diuretics
Optimal use of diuretics is the cornerstone of a successful HF treatment

regimen
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 symptoms
and 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

regimen

-
Initial use:
-
-
-
-
-
-

ACEIs and ARBs
Diuretics:

regimen

-
Initial use:
-
-
-
-
-
-

ACEIs and ARBs
Diuretics:
Diuretics:
PSAP 2013 Czvn:oiocv/Exnocv:xoiocv 93 Acu+v Dvcomvvxsz+vn Hvzv+ Fz:iuvv
Serum concentrations of AVP are elevated in patients with
HF, likely because of the lauer mechanisms. Two main
types of AVP receptors have cardiovascular and renal
enects. Te V
1a
receptor is located on the smooth mus-
cle of the systemic and coronary vasculature and causes
vasoconstriction.
Activation of this receptor increases anerload, increases
myocyte intracellular calcium concentrations, and con-
tributes to myocyte hypertrophy. In the distal tubules of
the nephron, activated V
2
receptors cause mobilization
of aquaporin-2 free water channels onto the apical mem-
brane of collecting duct cells, resulting in nuid retention.
Excess nuid retention contributes to hypervolemic hypo-
natremia, which, as previously mentioned, is a predictor
of poor cardiovascular outcomes in patients with HF.
Up-titration of loop diuretics not only increases natriure-
sis and diuresis, but also increases AVP release, leading
to continued or worsening hyponatremia. Blockade of
V
1a
and V
2
receptors causes vasodilation and aquaresis,
respectively. Arginine vasopressin receptor antagonists
oner a unique mechanism of nuid removal without dis-
rupting electrolyte concentrations or further activating
the neurohormonal system.
Two AVP receptor antagonists are currently avail-
able-conivaptan and tolvaptan. Conivaptan blocks
both V
1a
and V
2
receptors, whereas tolvaptan is primarily
a selective V
2
receptor antagonist. In studies, conivap-
tan failed to show improved hemodynamic end points,
exercise tolerance, or HF symptoms but was enective in
reversing hyponatremia (De Luca 2005). Tolvaptan has
FDA-approved labeling for the treatment of hypervolemic
or euvolemic hyponatremia (dehned as serum sodium of
less than 125 mEq/L or symptomatic hyponatremia resis-
tant to nuid restriction). Tis agent should be initiated in
the hospital seuing to monitor the rate of sodium correc-
tion. Rapid increases in sodium can cause severe adverse
enects such as osmotic demyelination, which can result in
irreversible neurologic complications or death.
In early studies, tolvaptan proved to be enective at
decreasing body weight, increasing urine output, reversing
edema, and correcting hyponatremia without signihcantly
anecting blood pressure, serum potassium, BUN, or SCr
(Schrier 2006; De Luca 2005). However, in the Acute and
Chronic Terapeutic Impact of a Vasopressin 2 Antagonist
(tolvaptan) in Congestive Heart Failure (ACTIV in CHF)
study, no dinerence was found between the tolvaptan
and placebo groups in the primary outcome of incidence
of worsened HF (dehned as death, hospitalization, or
unscheduled visits for HF) at 60 days. Tere was a trend
toward reduced mortality in tolvaptan-treated patients at
the end of the follow-up period, but the study was not pow-
ered to show such a dinerence (Gheorghiade 2004).
To determine whether initiating tolvaptan during an
ADHF episode anects mortality and HF rehospitalization,
the Emcacy of Vasopressin Antagonism in Heart Failure
Outcome Study with Tolvaptan (EVEREST) was conducted
(Konstam 2007). Tere were 2072 patients in the tolvaptan
group and 2061 patients in the placebo group. All patients
had an LVEF of less than 40% and showed signs of volume
overload with NYHA class III/IV symptoms. In addition
to standard therapy by their treating physician, participants
were randomized to tolvaptan 30 mg once daily or placebo
for at least 60 days. Primary end points included all-cause
mortality and the composite of cardiovascular death or HF
hospitalization. Median follow-up for the study population
was 9.9 months. During this time, 537 patients (25.9%)
and 543 patients (26.3%) died in the tolvaptan and placebo
groups, respectively (hazard ratio [HR] = 0.98; p=0.68);
this was within the predetermined noninferiority margin.
Te other composite primary end point of cardiovascular
death or hospitalization for HF occurred in 871 patients in
the tolvaptan group (42%) and 829 in the placebo group
(40.2%) (HR = 1.04; 95% conhdence interval, 0.951.14;
Table 1-3. Comparison of Loop Diuretics
Furosemide Bumetanide Torsemide Ethacrynic Acid
Equivalent intravenous doses 2040 mg 1 mg 20 mg 50 mg
Initial daily dose 2040 mg/day or
twice daily
0.51 mg/day or
twice daily
1020 mg/day 2550 mg/day or
twice 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 practice
guidelines. J Card Fail 2010;16:e1-e194.
Under Diuresis
J.B. is a 54-year-old African-American man with dilated cardiomyopathy (ejection
fraction of 25% on echocardiogram 1 year ago) being seen in the clinic today with a
7-day history of dyspnea on exertion and increased lower extremity and
abdominal swelling. J.B. has no other complaints. His weight has increased
from 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+ pitting
edema 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.
Over Diuresis
B.S. is a 48-year-old woman, with a history of idiopathic dilated
cardiomyopathy. While in the hospital for decompensated HF,
she continued her chronic drugs (lisinopril 20 mg/day and
carvedilol 25 mg twice daily) and also received intravenous
furosemide and oral metolazone. She has lost 5.5 kg since her
hospital admission 3 days ago. You notice that her blood urea
nitrogen concentration has increased to 61 mg/dL and
serum creatinine concentration to 2.5 mg/dL (blood urea
nitrogen 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 with
standing.
Persisting
symptoms?
Consider
digoxin, LVAD,
transplant
cardioverter-
defibrillator
No further
treatment required
QRS >120 msec?
Consider Cardiac
Resynchronization
Yes
Yes
Yes No
LVEF <35%
Yes
No
No
No
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Beta-blockers
ACE inhibitors
Aldosterone Antagonists
ARB
ARB
Beta-blockers
Vasodilating
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
AT
1
receptor
Ang I
Biological
effects
ACE
Non ACE pathways
Renin
enzyme
Aldosterone
Retention of
water and
salt
Ang = Angiotensin.
Excretion
of
potassium
Ang II
Angiotensinogen
ACE Inhibitor
ARB
Aldosterone Antagonist
Aldosterone Antagonists:
Spironolactone and Eplerenone
Add an aldosterone antagonist to

background ACE inhibitor and beta-
blocker therapy in patients with
symptomatic HF (NYHA class II-IV) and
an EF 40%
Aldosterone antagonists are

contraindicated in patients with:
-
Potassium >5.0 mEq/L
-
CrCl <30 mL/min (or SCr >2.5 mg/dL)
It is recommended that renal function

and potassium be measured at
baseline, then 1 week, 1 month, and
every 3 months
Zannad F, et al. N Engl J Med 2011;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
Heart Failure
Sympathetic nervous
system activation
Vasoconstriction
Renin
Angiotensin I
Angiotensin II
Aldosterone
Cardiac
Remodeling
Beta-blockers
ACE inhibitors
Aldosterone Antagonists
ARB
ARB
Beta-blockers
Hydralazine/Isosorbide
Vasodilating
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 increase
stroke volume and cardiac output
-
increase in nitric oxide bioavailability secondary to
reduction in oxidative stress
Nitric oxide attenuates myocardial remodeling and
may play a protective role in heart failure.
Cohn JN, et al. N Engl J Med. 1991;325(5):303310.
ACE inhibitors have a reduction in mortality Hydralazine/isosorbide dinitrate improves
exercise capacity
Hydralazine/isosorbide dinitrate vs ACE inhibitors in treatment of
HF with reduced EF
Hydralazine/Isosorbide dinitrate:
A Racist Drug?
White patients:
-
HF more likely secondary to CAD
and the activation of
neurohormonal mechanisms
Black patients:
-
HF more likely secondary to
hypertension related to a
vascular deficiency of nitric oxide
Recommended for black HF patients who

remain symptomatic despite optimal medical
therapy
-
Not a substitute for ACE inhibitors or ARB
Appropriate as first-line therapy in all HF

patients unable to tolerate either an ACE
inhibitor or ARB because of renal
insufficiency, hyperkalemia, or possibly
hypotension
Persisting
symptoms?
Consider
digoxin, LVAD,
transplant
cardioverter-
defibrillator
No further
treatment required
QRS >120 msec?
Consider Cardiac
Resynchronization
Yes
Yes
Yes No
LVEF <35%
Yes
No
No
No
Severity of Heart Failure
Modes of Death
MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial
in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.
12%
24%
64%
CHF
Other
Sudden
Death
n = 103
NYHA II
26%
15%
59%
CHF
Other
Sudden
Death
n = 103
NYHA III
56%
11%
33%
CHF
Other
Sudden
Death
n = 27
NYHA IV
85% of sudden death in HF from ventricular
arrhythmias
Implantable Cardioverter-Debrillator
(ICD)
Implantable Cardioverter-Debrillator
(ICD)
Persisting
symptoms?
Consider
digoxin, LVAD,
transplant
cardioverter-
defibrillator
No further
treatment required
QRS >120 msec?
Consider Cardiac
Resynchronization
Yes
Yes
Yes No
LVEF <35%
Yes
No
No
No
Cardiac Resynchronization Therapy
(CRT)
Cardiac remodeling can lead to
conduction irregularities and
dyssynchrony between the right
ventricle and left ventricle
-
Wide QRS (<120 msec)
-
Bundle branch block
Biventricular pacing or cardiac
resynchronization therapy (CRT)
The addition of CRT to an ICD
reduced rates of death and
hospitalization for HF
Indicated in patients who have
symptomatic HF, LVEF <35%, and a
widened QRS complex (>120 msec)
LV lead
RV lead
LV lead
RV lead
Cardiac Resynchronization Therapy
(CRT)
Cardiac remodeling can lead to
conduction irregularities and
dyssynchrony between the right
ventricle and left ventricle
-
Wide QRS (<120 msec)
-
Bundle branch block
Biventricular pacing or cardiac
resynchronization therapy (CRT)
The addition of CRT to an ICD
reduced rates of death and
hospitalization for HF
Indicated in patients who have
symptomatic HF, LVEF <35%, and a
widened QRS complex (>120 msec)
Persisting
symptoms?
Consider
digoxin, LVAD,
transplant
cardioverter-
defibrillator
No further
treatment required
QRS >120 msec?
Consider Cardiac
Resynchronization
Yes
Yes
Yes No
LVEF <35%
Yes
No
No
No
Digoxin:
Serum concentrations
Digoxin increases parasympathetic activity

-
Increases cardiac index and decreases preload
with little effect on blood pressure
Improves symptoms, exercise tolerance, and

quality of life in HF patients with reduced ejection
fraction
-
No mortality benefit has been shown
Serum digoxin concentrations of 0.50.8 ng/mL

are associated with the best outcomes
-
Levels over 1.2 ng/mL have been associated
with an increased morbidity/mortality risk
Digoxin:
Serum concentrations
Digoxin increases parasympathetic activity

-
Increases cardiac index and decreases preload
with little effect on blood pressure
Improves symptoms, exercise tolerance, and

quality of life in HF patients with reduced ejection
fraction
-
No mortality benefit has been shown
Serum digoxin concentrations of 0.50.8 ng/mL

are associated with the best outcomes
-
Levels over 1.2 ng/mL have been associated
with an increased morbidity/mortality risk
Digoxin
Bauman JL,et al. Arch Intern Med. 2006;166(22):2539-2545
Persisting
symptoms?
Consider
digoxin, LVAD,
transplant
cardioverter-
defibrillator
No further
treatment required
QRS >120 msec?
Consider Cardiac
Resynchronization
Yes
Yes
Yes No
LVEF <35%
Yes
No
No
No
LV Assist Device
LV Assist Device
LV Assist Device
Heart Transplant
Older age (usual limit 6065 y)
Active infection
Severe diabetes mellitus with other end-organ disease
Pulmonary function < 60%* predicted, or chronic
bronchitis
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 to
cardiac transplantation
Heart Transplant
Active infection
bronchitis
Heart Transplant
Active infection
bronchitis
Heart Transplant
Active infection
bronchitis
Drugs to avoid in patients with HF with
Drugs known to adversely affect the clinical status

of patients with current or prior symptoms of HF and
reduced LVEF should be avoided or withdrawn
whenever possible
-
NSAIDs
-
Antiarrhythmics: Class Ia, Class Ic, dronedarone
-
Non-dihydropyridine calcium channel blockers
-
Thiazolidinediones
Treatment for Heart Failure with
Hormonal therapies other than to replete

deficiencies are not recommended and may be
harmful to patients with current or prior
symptoms of HF and reduced LVEF.
Use of nutritional supplements as treatment for

HF is not indicated in patients with current or
prior symptoms of HF and reduced LVEF.
Heart Failure with Preserved
Ejection Fraction (HFPEF)
20 to 50 percent of patients with HF have a

preserved 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 with

HFPEF
Treat hypertension according to published

guidelines
-
Be wary of compelling indications such as
diabetes and left ventricular hypertrophy
Treat CAD according to published

guidelines
Control ventricular rate in patients with

HFPEF and atrial fibrillation
Use diuretics to control pulmonary

congestion and peripheral edema
Acute heart failure syndromes (AHFS)
New-onset, gradual, or rapidly worsening HF signs and

symptoms that require urgent therapy.
Predictors of Mortality Based on
Analysis of ADHERE Database
Three variables are the strongest predictors of mortality in
hospitalized acute decompensated HF patients:
Patients with all three characteristics had an in-hospital
mortality of 21.9 percent compared to 2.1 percent in
patients 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
Medical management of AHFS is based on
precipitating factors and clinical presentation
Identification of potential precipitating factors for acute
HF 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

In patients experiencing a HF exacerbation requiring
hospitalization:
-
Treatment with ACE inhibitors or ARBs should be continued in
most patients in the absence of hemodynamic instability
-
Continuation of beta blocker therapy is recommended in most
patients, unless they develop cardiogenic shock, refractory
volume 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 or
ARBs and beta-blocker therapy, initiation of these therapies is
recommended in stable patients prior to hospital discharge.
Medical management of AHFS is based on precipitating
factors and clinical presentation
Warm & Dry Warm & Wet
Cold & Wet Cold & Dry
Congestion at Rest?
Low Perfusion
at Rest?
I II
III IV
No
No Yes
Yes
Cardiac
Index
2.2
l/min/m
2
PCWP
18 mmHg
Evidence of low perfusion:
Cool extremities
Narrow pulse pressure
Low serum sodium
Renal dysfunction
Hypotension with ACE inhibitor
Altered Mental Status
Signs/symptoms of congestion:
Orthopnea/PND
JVD
Ascites
Edema
Rales
Congestion
H
y
p
o
p
e
r
f
u
s
i
o
n
Hemodynamic Monitoring
Swan-Ganz Catheter
Used when congestion and perfusion cannot be

determined from clinical assessment or when
symptoms persist despite empiric adjustment of
standard therapies
Allows measurement:
-
Right atrial pressure
-
Right ventricular pressure
-
Pulmonary artery capillary pressure ("wedge"
pressure)
-
Cardiac index
-
Systemic vascular resistance
PCWP
18 mmHg
Cold & Wet
Cold & Dry
I II
III IV
Cardiac
Index
2.2
l/min/m
2
Normal
Mild to Moderate
LV Dysfunction
Severe
LV Dysfunction
Acute Heart Failure Syndromes (AHFS)
Warm and Wet
T.J. is a 65-year-old man who came into the hospital with

increasing dyspnea at rest. A physical examination reveals
rales throughout his lung fields. His chest X-Ray showed
pulmonary congestion. He was diagnosed with AHFS.
Echocardiography revealed an LVEF of 45%. He has a
history of hypertension, hyperlipidemia, and coronary artery
disease with a three-vessel coronary artery bypass graft 2
years ago. T.J.s vital signs are BP 182/81 mm Hg and HR 85
beats/minute.
Warm and Wet
T.J. is a 65-year-old man who came into the hospital with

increasing dyspnea at rest. A physical examination reveals
rales throughout his lung fields. His chest X-Ray showed
pulmonary congestion. He was diagnosed with AHFS.
Echocardiography revealed an LVEF of 45%. He has a
history of hypertension, hyperlipidemia, and coronary artery
disease with a three-vessel coronary artery bypass graft 2
years ago. T.J.s vital signs are BP 182/81 mm Hg and HR 85
beats/minute.
A Swan-Ganz catheter reveals a cardiac index of 2.6 L/

minute/m
2
and pulmonary capillary wedge pressure (PCWP)
of 25 mm Hg.
PCWP
18 mmHg
Cold & Wet
Cold & Dry
I II
III IV
Cardiac
Index
2.2
l/min/m
2
Use drugs that reduce
preload (PCWP)
Diuretics
Vasodilators
Warm & Wet
Warm & Wet
Warm & Wet
Figure 1-3. Decision tree for the treatment of acute decompensated heart failure.
BiPAP = bilevel positive airway pressure; CO = cardiac output; CPAP = continuous positive airway pressure; DOE = dyspnea on exertion;
HJR = hepatojugular reex; IV = intravenous; JVD = jugular venous distension; NT-proBNP = N-terminal proB-type natriuretic
peptide; PND = paroxysmal nocturnal dyspnea; PO = oral; SBP = systolic blood pressure; SOB = shortness of breath; UOP = urine output.
Assess volume status
Consider careful IV
diuresis vs. uid bolus
if hypovolemic
vs
HF progression to low CO
Assess blood pressure
No Yes
On -blocker chronically
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
Patient with acute decompensated heart failure
Mild volume overload
IV diuretics
IV furosemide:
On oral furosemide as
outpatient: give 12 x
patient home dose as IV
bolus (max = 180 mg)
No oral furosemide as
outpatient: give 2040
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Requiring CPAP or BiPAP
SBP > 90 mm Hg SBP < 90 mm Hg
Low CO:
Pre-renal azotemia
Altered mental status
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
Dobutamine Milrinone
Continued signs/symptoms of low CO
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
Consider pulmonary artery catheter
Consider vasodilators aer known
hemodynamic parameters
Consider dopamine if severe
hypotension or cardiogenic shock
Assess response to initial diuretic
If UOP < 250500 mL aer 2 hours:
Double previous IV bolus dose
OR
followed by continuous infusion
OR
Double previous IV bolus dose + PO
metolazone or IV chlorothiazide
Reassess UOP as above, and if
ineective, consider moderate to
severe volume overload or low CO
IV diuretics +
IV vasodilators
IV diuretic: continue diuretic
regimen titrated to UOP goals
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
Ultraltration is also an option
for uid removal
IV loop diuretics should begin in the emergency

department or outpatient clinic without delay
-
Initial IV dose should equal or exceed chronic
oral daily dose
Urine output, daily weight, and signs and symptoms

of congestion should be serially assessed, and
diuretic dose should be titrated accordingly to
relieve symptoms and to reduce fluid excess
When diuresis is inadequate to relieve congestion

the diuretic regimen should be intensified using
either:
-
higher and more frequent doses of loop diuretics;
-
addition of a second diuretic (metolazone or IV
chlorthiazide); or
-
continuous infusion of a loop diuretic.
Warm & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
In patients with evidence of

severely symptomatic fluid
overload in the absence of
systemic hypotension, IV
vasodilators can be beneficial
when added to diuretics and/or
in those who do not respond to
diuretics alone:
-
Nitroglycerin
-
Nitroprusside
-
Nesiritide?
Warm & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
Warm & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
In patients with evidence of

severely symptomatic fluid
overload in the absence of
systemic hypotension, IV
vasodilators can be beneficial
when added to diuretics and/or
in those who do not respond to
diuretics alone:
-
Nitroglycerin
-
Nitroprusside
-
Nesiritide?
Effect of HF treatment should be monitored with

careful 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 systemic
perfusion and congestion
Daily serum electrolytes, blood urea nitrogen, and

serum creatinine concentrations should be measured
during the use of IV diuretics or active titration of HF
medications.
Cold and Wet
K.L., a 58-year-old man with a 3-year history of non-ischemic

cardiomyopathy, is admitted to the hospital for severe
shortness of breath and altered mental status. He has
gained 11 kg over the past 2 weeks (now weighs 120 kg) and
has had decreased urine output despite increasing his
diuretic dose. A physical examination reveals rales
throughout his lung fields. K.L.s blood pressure (BP) is 84/63
mm Hg.
Cold and Wet
K.L., a 58-year-old man with a 3-year history of non-ischemic

cardiomyopathy, is admitted to the hospital for severe
shortness of breath and altered mental status. He has
gained 11 kg over the past 2 weeks (now weighs 120 kg) and
has had decreased urine output despite increasing his
diuretic dose. A physical examination reveals rales
throughout his lung fields. K.L.s blood pressure (BP) is 84/63
mm Hg.
A Swan-Ganz catheter reveals a cardiac index of 1.6 L/

minute/m
2
and pulmonary capillary wedge pressure (PCWP)
of 25 mm Hg.
PCWP
18 mmHg
Cold & Wet
Cold & Dry
I II
III IV
Cardiac
Index
2.2
l/min/m
2
Use combination of:
Inotropes (I)
Diuretics (D)
Vasodilators (V)
I
D
V
I+V
D+V+I
Cold & Wet
Cold & Wet
Intravenous inotropic drugs are reasonable
for patients presenting with (1) severe
systolic dysfunction, (2) symptomatic
hypotension or (3) inability to maintain
systemic perfusion and preserve end-organ
performance
-
Dobutamine
-
Milrinone
-
Dopamine
Cold & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
Cold & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
Drug Dose 1 1 2 DA
Dopamine
0.5 - 3 mcg/kg/min 0 0 0 +++++
Dopamine 4 - 10 mcg/kg/min ++ ++++ ++ +++++ Dopamine
> 10 mcg/kg/min ++++ ++++ ++ +++++
Dobutamine
2.0 - 10 mcg/kg/min + +++++ +++ 0
Dobutamine
10 - 20 mcg/kg/min ++ +++++ +++ 0
Milrinone
0.375 to 0.75 mcg/
kg/min
0 0 0 0
Milrinone is a selective phosphodiesterase-3 inhibitor (PDE3) that
increases the level of cAMP by inhibiting its breakdown within the cell
Cold & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
Drug
Dose HR MAP PCWP CO SVR
Dopamine
Dobutamine
Milrinone
0.5 - 3 mcg/kg/min 0 0 0 0/+ -
3 - 10 mcg/kg/min + + 0 + 0
> 10 mcg/kg/min + + + + +
2.0 - 20 mcg/kg/min 0/+ 0 - + -
0.375 - 0.75 mcg/
kg/min
0/+ 0/- - + -
Cold & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
Dobutamine and milrinone are preferable over dopamine
when blood pressure is adequate
- Dobutamine reduces the systemic vascular resistance
and may not increase oxygen demands as much as
dopamine, and is preferable when systolic blood
pressure >80 mmHg
- Milrinone is not dependent upon adrenergic receptor
activity 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
Cold & Wet
Consider careful IV
if hypovolemic
vs
No Yes
Fluid overload:
Orthopnea/
PND
JVD
Rales
DOE/SOB
S3 or S4
HJR
NT-proBNP
Weight gain
Edema
Pulmonary edema
Assess signs
and symptoms
IV diuretics
IV furosemide:
mg as IV bolus
Moderate to severe
volume overload and
SBP > 90 mm Hg
Fatigue
Pre-renal azotemia
Poor response to IV
diuretic
Oxygen requirement
Low CO:
Pre-renal azotemia
UOP
Poor response to IV
diuretic
Cool extremities
Pulsus alternans
If uncertain of
hemodynamic status,
consider pulmonary
artery catheter
Very low CO
OR
OR
IV diuretics +
IV vasodilators
IV vasodilator
Nitroglycerin
Nitroprusside
Nesiritide
for uid removal
Dopamine should be initiated first for severe
hypotension
- Patients may not tolerate the vasodilating effects of
dobutamine or milrinone at low blood pressures
If dopamine at doses of 20 mcg/kg/min does not achieve
a MAP of 60-65 mm Hg, then norepinephrine can be
added
Selection of an inotrope
Hospital to Home
Questions?
Contact me:
Nicholas B. Norgard, Pharm.D. BCPS
University at Buffalo School of Pharmacy &
Pharmaceutical Sciences
Center of Excellence B3-322
Ofce: 716-645-4779
nnorgard@buffalo.edu

PHM 601 Heart Failure Lecture Slides

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PHM 601 Heart Failure Lecture Slides

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Heart Failure

Nicholas B. Norgard, PharmD, BCPS

HF is defined as a clinical syndrome that is characterized by specific

There is no single diagnostic test for HF because it is largely a clinical

Ways to define HF:

CAD is most common cause of HF

HF is defined as a clinical syndrome that is characterized by specific

There is no single diagnostic test for HF because it is largely a clinical

Ways to define HF:

CAD is most common cause of HF

HF is defined as a clinical syndrome that is characterized by specific

There is no single diagnostic test for HF because it is largely a clinical

Ways to define HF:

CAD is most common cause of HF

Each time the heart beats, a volume of blood is ejected. This

Ventricular stroke volume is the difference between the

The EDV is the filled volume of the ventricle prior to

The ESV is the residual volume of blood remaining in the

Abnormality seen in heart

Ejection Fraction can

Afterload - the force

Strength of ventricular contraction

If venous return is increased, the

Increased preload increases

Strength of ventricular contraction

If venous return is increased, the

Increased preload increases

Cardiac dysfunction precipitates

Compensatory mechanisms activate:

These compensatory changes over

Neck vein distention

Acute pulmonary edema

Increased central venous

Weight loss >4.5 kg in 5 days

Bilateral ankle edema

Decrease in vital capacity by

Tachycardia (HR>120 bpm)

Cornerstone of pharmacotherapy for patients with

Beta-blockade is recommended in all patients with

Beta-blockade improves LV function, patient well-

In hospitalized patients, treatment should be initiated

Initiate as soon as clinically stable

Begin with low doses and titrate slowly

Can be done more rapidly in hospital settings

Patients with mild congestion

Patients with moderate to severe congestion

In the absence of symptoms continue

Instruct patients that they may initially feel

Patients with mild congestion

Patients with moderate to severe congestion

In the absence of symptoms continue

Instruct patients that they may initially feel

Patients with mild congestion

Patients with moderate to severe congestion

In the absence of symptoms continue

Instruct patients that they may initially feel

Cornerstone of pharmacotherapy for patients with heart failure

An ACE inhibitor is recommended in all patients with symptomatic HF

Treatment with an ACE inhibitor improves LV function, patient well-

In hospitalized patients, treatment should be initiated before

Aim for dose shown to reduce mortality in

Monitor SCr and K+ before and 1-2 weeks

Symptomatic hypotension and renal

An ARB is recommended in patients with