Download Treatment of Heart Failure - familypracticeresidency.org

David W Kabel MD FACC
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NH activation is an acute adaptation that
initially allows BP and cardiac output to be
maintained
NH activation rapidly becomes detrimental
Vasoconstriction is a hallmark of untreated LV
dysfunction
Starts a self perpetuating cycle of cell death and
remodelling with further NH activation
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Pump failure is sensed as hypovolemia
RAS activation leads to increases levels of
angiotensin II
ANS activation leads to increased circulating
catecholamines
Hyperaldosteronism
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Myocyte dysfunction and cell death
Remodeling occurs
LV dilatation
 Increased wall stress
 Ischemia
 Energy depletion
 Interstitial fibrosis
 More NH activation
 Mitral regurgitation
 Change from ellipsoid to spherical shape
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Relieve Symptoms
Improve LV function-both systolic & diastolic
Reduce hospitalizations
Improve prognosis
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Increased ejection fraction is associated with improved
prognosis
Diastolic function can also improve
Manage expectations
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Pharmacologic
Diuretics
 Neurohormonal inhibitors
 Antiarrhythmic drugs
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Device therapies
AICD
 Resynchronization therapy
 LV assist devices
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Adjunctive measures
Diet
 Fluid restriction
 Home monitoring
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Treat co-morbidities according to guidelines
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Hypertension!-Systolic BP<120
Diabetes-some hypoglycemic drugs may worsen HF
Lipid abnormalities
Sleep apnea!
Atrial fibrillation
Avoid drugs which may exacerbate HF
Anti-arrhythmic drugs other than amiodarone and dofetilide
 Calcium blockers-verapamil, diltiazem
 NSAIDS
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 Sodium retention
 Inhibit effects of diuretics, ACEIs and ARBs
 Renal toxicity
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Monitor
Weight
 Blood pressure
 Renal function
 Home health monitoring can reduce hospital
admissions
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Regular low to moderate physical activity
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Medicare now pays for Cardiac Rehab for CHF
Avoid dietary indiscretion
Stop smoking
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First goal is to achieve euvolemia
Initiate therapy to block neurohormonal
activation
Treat comorbidities
Most patients can be treated effectively with
inexpensive generics
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Relieve symptoms faster than any other drugs
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Relieve dyspnea
Reduce edema
Improve exercise tolerance
Only drugs that control fluid retention
Should not be used alone in symptomatic
patients
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Increase sodium excretion by 20-25%
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Enhance free water clearance
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Maintain efficacy in reduced GFR
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Increase sodium excretion 5-10%
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Reduce free water clearance
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Lose effectiveness with decreased GFR
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Better antihypertensive drugs than loop
diuretics
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Longer duration of action
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Too little
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Too much
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Fluid retention
Reduced effectiveness of other therapies
Volume contraction
Hypotension
Hyponatremia
Renal insufficiency
Right dose may be difficult to determine
Dosage requirements change with change in
clinical status
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Initiate with loop diuretics
Furosemide most common
Torsemide or butenamide may work better in a
few patients, especially with deteriorating renal
function
Start low dose once a day
Titrate up and go to BID dosage as needed
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I like AM and noon schedule
Reduces nocturia
Restrict dietary sodium
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Maintenance therapy may require lower doses
than at initiation
Monitor electrolytes frequently
Some class I and II patients may not need any
diuretics for a time
Consider lower dose while up-titrating other
drugs, especially if BP is low
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Fluid retention may result in poor absorption
from GI tract
Reduced GFR requires increased dose of loop
diuretics
Intermittent IV loop diuretics
Combination therapy
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Add metolazone
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Electrolyte imbalance-sodium, potassium, and
magnesium
Volume contraction
Hypotension
Azotemia
Hearing loss
Hypotension, fluid retention, and azotemia
together have a poor prognosis
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Block effects of circulating catecholamines
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Sympathetic activation initially beneficial to increase
cardiac output
Long term ANS activation is deleterious
 Increased LV volume and pressure overload
 Vasoconstriction
 Impaired renal sodium excretion
 LV hypertrophy and dilatation
 Myocardial fibrosis
 Arrhythmias
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Benefits outweigh negative inotropic effects
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Three drugs are approved for use in HF
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Carvedilol
Metoprolol succinate
Bucindolol
All patients with reduced EF should receive
beta blockers unless contraindicated
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Reduced mortality
Increased EF
Symptomatic relief
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Do not start until vascular congestion is
relieved
Start at same time as ACEI or ARB
Effects are additive
 Small doses of both are more effective than higher
dose of a single drug
 Even a small dose is better than none
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Use with caution with COPD or bradycardia
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Initiate at small doses
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Titrate up every 2-4 weeks as tolerated
Monitor fluid balance
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Unless replacing another beta blocker
Daily weights
Continue even if clinical improvement is not
evident
Avoid abrupt withdrawal
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Worsening CHF and fluid retention
Increase diuretics
 Can usually continue beta blockers
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Fatigue
Often resolves in a few days or weeks
 Reduce dose or change to a different drug
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Hypotension
Often occurs for 1st 24-48 hours
 Decrease diuretic dose
 Give beta blocker and ACEI at different times of day
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Bradycardia and heart block
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May require pacemaker
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Best studied of RAS inhibitors
First class of drugs shown to improve EF and
prognosis
Prevent conversion of Angiotensin I to
Angiotensin II
Modifies LV remodelling possibly more than
ARBs
All ACEIs equivalent
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Tissue ACEI?
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Improve symptoms and clinical class
Reduce SCD
Reduce combined risk of hospitalization and
death
Improve outcomes in presence or absence of
CAD
Improvement occurs in all NYHA classes
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Prevent Angiotensin II from attaching to vascular
receptors-Prevents vasoconstriction
Modify LV remodelling perhaps less than ACEIs
Less data than ACEIs but clinical effects are similar
Fewer hospitalizations and deaths
 Seen in all NYHA classes
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May be better than ACEIs in preventing atrial
fibrillation
Most commonly used for patients who develop
cough while taking ACEIs
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Use in all patients with reduced EF unless
contraindicated
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Even Class I
Use with beta blockers
Use with diuretics if fluid retention
Start at low doses and titrate up unless
hypertensive
Check BMP at 1-2 weeks and q3-6 months after
that
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Tolerated by 85-90% of patients
Try to achieve maximum dose
Symptomatic relief may come in a few days or
several months
Continue treatment even in absence of
symptomatic improvement
Don’t delay beta blockers while titrating up
Avoid NSAIDs
No data supporting ACEIs and ARBs in same
patient-some data against it
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Avoid in:
Hx of angioneurotic edema-high incidence of crossreactivity between ACEIs and ARBs
 Oliguric renal failure
 Pregnancy
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Use with caution in:
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Hypotension
Creatinine>2.0
Bilateral renal artery stenosis
Serum potassium >5.0
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Spironolactone and Elperenone (Inspra)
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Main advantage of Inspra is decrease in side effectsbreast pain, GI, but much more costly
Block effects of aldosterone in renal tubule
Enhance effects of loop diuretics
Increased sodium excretion
Potassium retention
Most difficult drugs to use in HF
Under-utilized even by experts who advocate
increased usage
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Added after beta blockers and ACEIs, ARBs
Should be used with caution in absence of loop
diuretic or thiazide
Monitoring aldosterone antagonists-AHA
recommendations for K+ and renal monitoring
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3 days
7days
Monthly for 3 months
3-6 months after that
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Both venous (nitrate) and arterial (hydralazine)
vasodilatation
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Both preload and afterload reduction
Reduce mortality but not hospitalizations
Inferior to ACEIs, ARBs
Frequent side effects
Headache
 GI symptoms
 Lupus like syndrome
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Most effective in African-American patients when
added to standard therapy
Suitable alternative for patients intolerant to ACEIs
and ARBs
Angioneurotic edema
 Azotemia
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May be added to standard therapy if patient
remains hypertensive
Compliance may be an issue
Large number of pills
 TID dosage
 Nitrate tolerance
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Only indication is for rate control in atrial
fibrillation
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If beta blockers are ineffective
Should consider pacemaker & AV node ablation
instead
Has mild positive inotropic effects
Dosage-Never exceed 0.125 mg daily-less if
decreased GFR
Followup to AFFIRM trial showed 40%
increased all cause mortality for AF patients on
digoxin
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Look for reasons to DC the drug
Avoid in patients with recent MI or ischemia
Toxicity enhanced by hypokalemia, hypoxia,
thyroid disease
Side effects
Bradycardia and heart block
 Re-entrant tachycardias
 Anorexia, weight loss, nausea
 Visual disturbances-yellow vision, hoarfrost
 Mental status change
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Achieve euvolemia
Start beta blockers and ACEIs, ARBs at low doses
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Push beta blockers faster-more effect on prognosis
May increase both at once depending on BP
Titrate up q2-4 weeks
BMP on each visit
 May have to go slowly in elderly
 Maximum dose determined by BP, renal function
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Inform patient of possible side effects
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Fatigue
 May disappear after several days
 Ask patient to stick with therapy
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Lightheadedness
 Hypotension may require dose reduction
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Drug specific side effects
Increase meds to maximum tolerated dosage
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Check LV function after 3-4 months of
maintenance therapy
Add spironolactone
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Add hydralazine-nitrates
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If little or no improvement in EF
If loop diuretics and metolazone ineffective
In African-American patients
If response to standard Rx inadequate
Add additional antihypertensives to achieve
systolic BP of <120
If BP not controlled with standard Rx
Hydralazine
Amlodipine-Only calcium blocker to use in LV
dysfunction
 Clonidine
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30% of patients with low EF and Class III-IV
symptoms have QRS>120 msec
Mechanical consequences of dysynchrony
Suboptimal LV filling
 Reduced rate of rise of LV contractility
 Prolonged duration of mitral regurgitation
 Paradoxical septal motion
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Dysynchrony increases mortality
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Pacemaker therapy-Biventricular
Three leads
Right atrium if in sinus rhythm
 Right ventricular apex
 Coronary sinus for left ventricular pacing
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LV and RV are paced in synchronous fashion
Septum contracts with rest of LV
 May require echo guided adjustments
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Novel agent designed to slow HR in systolic HF
and EF<40% already on beta blockers.
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Sinus rhythm
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Target HR 50-60 bpm
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Demostrated that lower resting HR correlated with
improved prognosis
Does not lower BP
Systolic Heart failure treatment with
the If inhibitor ivabradine Trial
Heart rate at baseline influences the effect of
ivabradine on cardiovascular outcomes in
chronic heart failure:
analysis from the SHIFT study
Effect of ivabradine on outcomes in patients with chronic heart failure and HR 75
bpm
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
To assess the effect of ivabradine on outcomes
in heart failure patients on recommended
background therapies with heart rates ≥75 bpm
in the SHIFT trial
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Ivabradine
Placebo
n=2052
n=2098
Mean age, years
60
60
Male, %
77
77
BMI, kg/m2
28
28
Mean HF duration, years
3.4
3.4
HF ischemic cause, %
66
65
NYHA class III, %
50
51
NYHA class IV, %
2
2
Mean LVEF, %
28.7
28.5
Mean HR, bpm
84.3
84.6
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Ivabradine
Placebo
n=2052
n=2098
87
88
At least half target dose
55
56
At target dose
26
26
ACE inhibitors/ARBs, %
90
90
Diuretics (excludes AAs), %
85
83
Aldosterone antagonists, %
63
61
β-Blockers, %
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on primary outcome
CV death or hospitalization for HF
Patients with primary composite end point (%)
Hazard ratio=0.76
P<0.0001
40
Placebo
30
Ivabradine
20
10
0
0
6
12
18
24
30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine
on cardiovascular death
Hazard ratio=0.83
Patients with cardiovascular death (%)
30
P=0.0166
Placebo
20
Ivabradine
10
0
0
6
12
18
24
30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on hospital admission
for worsening heart failure
Hazard ratio=0.70
Patients with cardiovascular death (%)
30
Placebo
P<0.0001
20
Ivabradine
10
0
0
6
12
18
24
30
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on major
outcomes
Hazard
ratio
P
95% CI
Primary composite end point
0.76
0.68-0.85
Cardiovascular mortality
0.83
0.71-0.97
0.70
0.61-0.80
0.61
0.46-0.81
<0.000
1
0.83
0.72-0.96
0.0006
0.82
0.75-0.90
0.0109
0.79
0.71-0.88
<0.000
1
Hospitalization for worsening HF
Death from HF
All-cause mortality
All-cause hospitalization
Any cardiovascular hospitalization
0.20
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
0.40
0.60
Favors ivabradine
<0.000
1
0.0166
0.80
1.00
1.20
Favors placebo
<0.000
1
www.shift-study.com
Effect of ivabradine on outcomes
according to HR achieved at 28 days
Patients with primary composite end point (%)
40
 75 bpm
30
70 to <75 bpm
65 to <70 bpm
60 to <65 bpm
20
<60 bpm
10
0
0 Day 28
6
12
18
24
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Effect of ivabradine on outcomes
according to magnitude of HR reduction
Patients with primary composite end point (%)
40
 0 bpm
-10 to <0 bpm
30
< -10 bpm
20
10
0
0 Day 28
6
12
18
24
Time (months)
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
Conclusions
 In HF in sinus rhythm with HR ≥75 bpm heart rate
reduction with ivabradine improves outcomes, including
all-cause death and cardiovascular death reduces
§ Ivabradine-associated risk reductions are related to both
HR achieved and magnitude of HR reduction
§ Patients achieving <60 bpm or with >10 bpm reduction
have the best prognosis
Böhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22
www.shift-study.com
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Younger than normal patient population
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Less that optimal doses of beta blockers
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Ivabradine can cause atrial fibrillation
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Useful in limited number of patients
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Cost
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Neprilysin degrades several vasoactive
peptides
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BNP,bradykinin, adrenomedullin
Neprilysin inhibition increases levels of
natiuretic peptides, thus counteracting RAS
activation
LCZ696 compared to enalapril
Combination of valsartan with neprilysin
inhibitor sacubitril
Would LCZ696 improve outcomes over
enalapril?
Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Kaplan–Meier Curves for Key Study Outcomes, According to Study Group.
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Adverse Events during Randomized Treatment.
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Primary and Secondary Outcomes.
McMurray JJV et al. N Engl J Med 2014;371:993-1004
Conclusions
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Neprilysin inhibition is similar to other effective
therapies
Beta blockers
 ACEI, ARB
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Blocks neurohormonal activation
Appropriate for most patients with HF
Elderly
 Atrial fibrillation
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Will probably become part of standard CHF
regimen
Cost will be a factor
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EF less than 35%
LBBB with QRS >150 msec
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HFSA recommends for QRS >120
RV pacing with EF <35% should be upgraded
to CRT
MADIT II trial showed benefit for Class I-II
patients
Usually combined with AICD
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Depends on patient preferences and prognosis
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Improves LV contraction
Increases EF by 5-10% (or more)
Reduces mitral regurgitation
Improves hemodynamics
Clinical improvement
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Symptoms may improve by 1-2 classes
QOL improvement
Improved exercise tolerance and O2 comsumption
Reduced hospitalizations
Improved survival
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New generation of ICDs can monitor volume
status by measuring thoracic impedance
Can be measured in office with a programmer
Optivol by Medtronic
Detects fluid retention before clinical signs and
symptoms
Can help to determine if symptoms are due to
fluid retention
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Allows early intervention
Prevents hospitalizations
Outpatient IV diuretics
Enhances standard therapy
Devices have alarms but FDA requires them to
be turned off
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Strict criteria for implantation-Eligibility
limited
Indications
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EF< 35% with Class IV symptoms refractory to
standard therapy
Refractory VT and VF
LVAD used to be considered bridge to
transplant
LVAD now may be destination therapy for
some patients
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Often the most difficult aspect of therapy
Disease is progressive
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Therapy tends to become less effective over time
Most patients with HF will die of it
Need to be honest with patient and family
Get 2nd opinion if necessary
May benefit from Hospice or Palliative Care
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Timing is difficult
Prognosis less certain than with cancers and
neurologic diseases
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World Health Organization reports worldwide
mortality rate holding steady at 100%The Onion
We physicians don’t prevent anything, we
merely postpone-Anonymous