Heart failure update 2012

Heart Failure
Update 2012
John Hakim, MD, FACC
Southern Maryland
Hospital
Food for thought

Outlineof CHF Talk.
 Definition
 Pathophysiology
 Medical Treatment
 Mechanical Treatment
 Device Treatment
 Transplantation Option
 Future Hopes and Dreams

Definition of Heart Failure
• HF 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.
 In systolic heart failure the dominant feature is a
reduction in cardiac output
 In diastolic heart failure the dominant feature is
impaired filling of the left ventricle.

Heart Failure is a Major and Growing
Public Health Problem in the U.S.
Approximately 5 million patients in this
country have HF
Over 550,000 patients are diagnosed with HF
for the first time each year
Primary reason for 12 to 15 million office
visits and 6.5 million hospital days each year
In 2001, nearly 53,000 patients died of HF as
a primary cause

Heart failure is a major cause of
Hospitalization

Heart Failure is Primarily a
Condition of the Elderly
The incidence of HF approaches 10 per
1000 population after age 65
HF is the most common Medicare
diagnosis-related group
More dollars are spent for the diagnosis
and treatment of HF than any other
diagnosis by Medicare

New York Heart Association
Classification.
 Class I Physical activity is not limited and does
not cause significant fatigue, heart
palpitations, trouble breathing, or chest pain.
 Class II Physical activity is somewhat limited.
You are comfortable at rest, but ordinary activity
causes fatigue, heart palpitations, trouble
breathing, or chest pain.
 Class III Physical activity is markedly limited.
You are comfortable at rest, but less-than-
ordinary activities cause fatigue, heart
palpitations, trouble breathing, or chest pain.
 Class IV All physical activity causes discomfort.
Symptoms also are present at rest. Minor
physical activity always makes symptoms worse.

Prognosis
 Class IV has 30 to 70% annual
mortality
 Class III has 10 to 20% annual
mortality
 Class II has 5 to 10% annual
mortality

Character of Heart failure
Signs and symptoms of intravascular
and interstitial volume
overload, including shortness of
breath, rales, and edema
Manifestations of inadequate tissue
perfusion, such as impaired exercise
tolerance, fatigue, and renal
dysfunction.

Right Sided Heart failure
 Fluid retention without dyspnea or
rales.
 Often associated with weight
gain, dilation of the right ventricle.
 The focus of this talk is Chronic Left
Sided Heart failure.

Types of Left sided Heart failure
 Systolic dysfunction- reduced LV ejection
fraction.
 Diastolic dysfunction- increased
ventricular stiffness or impaired
myocardial relaxation. Often with
preserved LV ejection fraction.
 Physiologic states where the heart cannot
compensate for increased circulation or
metabolic requirements. (Regurgitatant
valvular disease, intra cardiac
shunts, disorders of heart rate or rhythm.)

Causes of CHF
Structural abnormalities (congenital or acquired)
that affect the peripheral and coronary arterial
circulation, pericardium, myocardium, or cardiac
valves, thus leading to the increased
hemodynamic burden or myocardial or coronary
insufficiency responsible for heart failure;
Fundamental causes, comprising the biochemical
and physiological mechanisms, through which
either an increased hemodynamic burden or a
reduction in oxygen delivery to the myocardium
results in impairment of myocardial contraction;
and

Etiology of Heart failure
 Any condition that causes myocardial
necrosis or chronic pressure or
volume overload can cause CHF.
 Hypertension is a factor in 75% of
patients.

Classical Symptoms of Heart Failure
 Fatigue or inability to exercise well; having less energy, feeling more
tired than usual;
 Dyspnea at rest or exertion.
 Paroxysmal nocturnal dyspnea shortness of breath while sleeping or
that wakes you at night
 Orthopnea-Shortness of breath while lying down, gets worse when you lie flat
 Cough – can be wet or dry, with crackles, and usually worse with lying
down.
 Weight gain
• Swelling in the feet or ankles, usually worse at the end of the day or
after standing for long periods; shoes may no longer fit.
• Sometimes edma is painful but usually pressure indents the skin
• Abdominal swelling with decreased appetite and decreased muscle
strenght (Cardiac Chachectia)
• Abdominal distention (Ascites) usually a sign of right heart failure.
 Urination
• frequent urination, usually at night. Increased urination (Due to high
BNP)

Signs of heart failure
 Exertional dyspnea
 Orthopnea
 Gallup sounds
 Lung Crepitations
 Pulmonary edema
 Edema

Acute Heart Failure Symptoms
 Caused by rapid fluid buildup in the
lungs (congestion, pulmonary
edema). Symptoms develop
suddenly and may include:
 Severe shortness of breath.
 An irregular or rapid heartbeat.
 Coughing up foamy, pink mucus.

COMMON CAUSES OF
SYSTOLIC FAILURE
 Ischemic Heart disease and Prior MI account for
2/3 of systolic heart failure
 Essential Hypertension is a major cause of
ischemic and non ischemic systolic heart failure
 Hypertension increases afterload and accelerates
the progression of heart failure. HTN causes
chronic pressure overload.
 Other causes of Non ischemic heart failure are
genetic diseases, Toxic/drug induced, Immune
mediated, infiltrative process, Metabolic disorders

All-cause Mortality vs LVEF (Median 29%)
Survival
Probability
Time (days)
LVEF<30%
LVEF≥30%*
*p=0.005 vs
LVEF<30%

Cause of Systolic Heart failure
Acquired vs Genetic Causes
• Acquired Causes
• Hypertension
• Diabetes
• Dyslipidemia
• Valvular heart disease
• Coronary or peripheral vascular
disease
• Myopathy
• Rheumatic fever
• Mediastinal irradiation
• Sleep Apnea
• Exposure to cardiotoxic agents
(Adrianomycin, Danaurubicin, Em
brel)
• Current and past alcohol
consumption
• Smoking
• Collagen vascular disease
• Exposure to sexually transmitted
diseases
• Thyroid disorder
• Pheochromocytoma
• Obesity
 Genetic Causes
 Predisposition to
atherosclerotic disease or
Valvular disease
 (Hx of MIs, strokes, PAD)
 Sudden cardiac death
 Myopathy
 Conduction system disease
(need for pacemaker)
 Tachyarrhythmia
 Cardiomyopathy
(unexplained HF)
 Skeletal Myopathy

Complications of Chronic Heart
failure
 An irregular heartbeat leading to
death (VT)
 A stroke leading to death
 A heart attack leading to death
 Deep vein thrombosis
 Pulmonary embolism
 Anemia
 Cognitive impairment
 Mitral valve regurgitation

Common test ordered in CHF
medical history and a physical exam.
Lab tests
Electrocardiogram
Chest X-ray.
Echocardiogram
Brain natriuretic peptide (BNP)/ TSH/
 Nuclear stress test/MUGA
 Cardiac catheterization.

DIASTOLIC HEART FAILURE
 Patients with symptoms and signs of Heart
Failure with normal systolic function and
diastolic dysfunction.
• 30 to 50% of patients with Heart failure
symptoms have normal LV systolic function.
• Abnormal LV filling and elevated filling
pressures.
• Usually due to Impaired relaxation of the LV
and increased stiffness of the cardiac muscle.
 Most prevalent in patients over 75 years
old.

Copyright ©2000 BMJ Publishing Group Ltd.
Jackson, G et al. BMJ 2000;320:167-170
Hypertrophic Cardiomyopathy

Pathogenesis of Diastolic Heart
Failure
 Pathologic Myocardial hypertrophy
• HTN, Hypertrophic Cardiomyopathy
 Aging
 Ischemic fibrosis
 Restrictive Cardiomyopathy
• Infiltrative disorders (Amyloid, Sarcoid)
• Storage Diseases (Hemochromatosis)
 Endomyocardial disorders
 Valvular heart disease
• (obstructive or regurgitation)

DIASTOLIC HEART FAILURE
usually due to Hemodynamic stress
 Patients with diastolic heart failure do not
tolerate hemodynamic stress well
 Atrial fibrillation causes loss of atrial contraction
and often leads to Diastolic CHF
 Tachycardia shortens diastole and leads to CHF
 Elevation in BP worsens myocardial relaxation
 Ischemia worsens diastolic function raising
LA and PA pressures. (This is why ischemia
causes SOB)
 Aortic Stenosis causes worsening diastolic
function.

Diastolic CHF
All treatments are empiric(No trial data)
 2005 ACC/AHA guidelines supports 4
treatments of diastolic CHF
• Control of systolic and diastolic HTN
• Control of atrial rate in patients with A
fib
• Control of pulmonary congestion and
edema with diuretics
• Coronary revascularization of patients
with CAD, where ischemia causes worse
diastolic function.

Diastolic Heart Failure often presents with
Acute Pulmonary Edema
 Treatment
• Loop diuretics (furosemide)
 Both immediate action to dilate pulmonary
arteries and longer action to diurese
• Afterload Reduction
 Nitrates
 Morphine
 Ace inhibitors (Captopril, enalapril, etc)

Systolic Heart Failure
The ballooning of the Heart

Heart Failure Pathophysiology (the whole body participates)

Neurohormonal activation
Decreased cardiac output activates
many neuro-hormonal compensatory
systems that in the short term act to
preserve circulatory hemostasis and
maintain arterial pressure.
When in excess these systems play a
role in worsening of CHF

Medical Treatment of Systolic Heart Failure
What Improves Survival
 ACE inhibitors
 Beta Blockers
 Spironolactone (Aldactone)
/Eplenrone (Inspira)
 -Hydralazine and Nitrates (V-Heft)
 Angiotensin Receptor Blockers (ARB)
 Device Therapy (AICD)

DIURETICS
Sodium and Water retention are the
hallmark of CHF and diuretics are
mandatory treatment for patients with
pulmonary or Peripheral edema.
Patients with CHF should be encouraged to
weigh themselves daily and seek advice if
a weigh gain of more than 1.5kg in 24 hrs

Why give ACE inhibitors?
Directics activate the Renin Angiotensis
system and should be given in
combination with and ACE inhibitor.
Correction of fluid overload with diuretics
should be undertaken before starting an
ACE inhibitor.
Adding an ACE inhibitor to a patient on high
dose diuretic may result in significant first
dose hypotension.

ACE-INHIBITORS
ACE inhibitors relieve symptoms, reduce
hospitalizations and improve survival in
patients with systolic and diastolic heart
failure and should be used regardless of
the severity of CHF.
Patients with the lowest EF derive the
greatest benefits from ACE inhibitors.
The evidence that ACE inhibitors improve
survival and symptomatic wellbeing is
incontrovertible.

Beta Blocker- Why do they work
In heart failure, the nervous system is over
stimulated. Norepinephrine levels rise.
Increased levels of circulating
norepinephrine cause heart remodeling
and arrhythmias.
High levels of norepinephrine are directly
toxic to heart cells and increase risk of
death.
Beta Blockers – block the toxic effect of
nervous system over stimulation and
norepinephrine.

Normal
The Normal Heart is a 1-Organ That
Functions in a 1 -Environment
1
1
1 2
1
1
2
1
1
1
1 11

Normal Heart failure
Heart Failure Converts the Circulation
From a 1- to a 1/ 2 / 1- Environment
1
1
1 2
1
1
2
1
1
1
1 11
2
1
1 1
2
1
1
1
2
2
1 21 2
1
1

NE NE
NE
Cardiac cell toxicity
Carvedilol
1 2 1
Metoprolol
Cofactors

[123I]mIBG Planar Imaging for Cardiac Assessment
Normal innervation NHYA Class II NYHA Class IV
Quantitation of cardiac uptake of [123I]mIBG expressed in terms
of the ratio of counts/pixel between regions of interest (ROIs)
drawn around the heart (H) and in the upper mediastinum (M),
the H/M ratio.
H/M ratio: 2.2 1.7

Results of Direct Comparison Trials with
Metoprolol and Carvedilol in CHF Patients
LV Ejection
Fraction (%)
0
+2
+4
+6
+8
+10
+12
Metoprolol
(n=123)
Carvedilol
(n=125)
Packer M et al. Am Heart J 2001;141(6):899-907
P = 0.009

BETA-BLOCKERS
 BETA-BLOCKERS inhibit the adverse
effects of chronic activation of the
sympathetic nervous system acting
on the myocardium
 Patients with minimal symptoms
(NYHA 2) derive little symptomatic
benefit from beta blockers.

BETA-BLOCKERS
Beta-BLOCKERS approved for the
management of CHF are:
Carvedilol, Metoprolol and bisoprolol.
 All three drugs have been shown to
prolong survival but they are not the
same.

Primary Argument Supporting the Belief
That Only 1 -Blockade is Important
Mortality results in earlier large-scale trials
MERIT-HF (metoprolol) 34% in risk
CIBIS-2 (bisoprolol) 34% in risk
COPERNICUS (carvedilol) 35% in risk

0.60 0.80 1.00
-blocker
better
-blocker
worse
- only
32 Post-Infarction
Trials (n=26,580)
Usual
antisympathetic blockade

0.60 0.80 1.00
-blocker
better
-blocker
worse
- only
-blockers
with ISA
32 Post-Infarction
Trials (n=26,580)
Less than usual
Usual

-1 + -2
and/or -1
0.60 0.80 1.00
-blocker
better
-blocker
worse
- only
-blockers
with ISA
32 Post-Infarction
Trials (n=26,580)
More than usual
Less than usual
Usual

-1 + -2
and/or -1
0.60 0.80 1.00
-blocker
better
-blocker
worse
- only
-blockers
with ISA
= 13%
32 Post-Infarction
Trials (n=26,580)

-1 + -2
and/or -1
0.60 0.80 1.00
-blocker
better
-blocker
worse
0.50 0.75 1.00
-blocker
better
-blocker
worse
- only
-blockers
with ISA
= 13%
32 Post-Infarction
Trials (n=26,580)
27 Heart Failure
Trials (n=15,851)
1.25

-1 + -2
and/or -1
0.60 0.80 1.00
-blocker
better
-blocker
worse
0.50 0.75 1.00
-blocker
better
-blocker
worse
- only
-blockers
with ISA
= 13% = 13%
32 Post-Infarction
Trials (n=26,580)
27 Heart Failure
Trials (n=15,851)
1.25

Metoprolol
(selective blockade)
Carvedilol
(comprehensive
blockade)
Baseline
1020 deaths
COMET Study Design
3029 pts
class II-III CHF
LVEF < 35%

Metoprolol
tartrate
Carvedilol
3.125 mg BID
Baseline
6.25 mg BID
12.5 mg BID
1020 deaths
COMET Study Design
5 mg BID
12.5 mg BID
25 mg BID
3029 pts
class II-III CHF
LVEF < 35%
25 mg BID
50 mg BID

Packer M et al. Am Heart J. 2001;141:884–888.
+ 12
+ 6
0
– 6
– 12
– 18
– 24
P=.009 P=.072
LV Ejection
Fraction (%)
LV End-Diastolic
Volume (mL/m2)
+ 12
+ 10
+ 8
+ 6
+ 4
+ 2
0
Metoprolol (n=123)
Carvedilol (n=125)
Mean duration 8.75 mos
Comparison of Carvedilol With
Metoprolol on LV Function

COMET
(Carvedilol or Metoprolol European Trial)
 Compares comprehensive 1-, 2-, 1-blockade
with carvedilol to 1-selective blockade with
metoprolol tartrate
 Prespecified end points: all-cause
mortality, combined risk of all-cause mortality
and hospitalization
 More than 3000 patients with class II–IV heart
failure due to ischemic or nonischemic
Cardiomyopathy
• With over 1020 events, COMET is the largest
trial ever conducted in heart failure
 Intended follow-up was at least 3.5 years
• 10,000 patient-years makes COMET the longest trial
ever conducted in heart failure
Poole-Wilson PA et al. Eur J Heart Fail. 2002;4:321–329.

Randomized
(No run-in phase)
3029 patients with stable heart failure, New York Heart Association
Class II–IV, receiving standard treatment including ACE inhibitors
Time to 1020 deaths
Estimated to be 4 to 6 years
Screening Titration to
maximum
tolerated
or target dose
(Start: carvedilol 3.125 mg bid, metoprolol tartrate 5 mg bid)
Assessments every 4 months
during maintenance phase
(n 1500) Metoprolol 50 mg bid
(n 1500) Carvedilol 25 mg bid
Poole-Wilson PA et al. Eur J Heart Fail. 2002;4:321–329. Poole-Wilson PA et al. Lancet. 2003;362:7–13.
COMET Study Design

Time (years)
PercentageMortality(%)
0
10
20
30
40
0 1 2 3 4 5
Relative
risk
95% CI P value
Carvedilol vs
Metoprolol
0.83 0.74–0.93 .0017
Metoprolol
Carvedilol
Effect of Carvedilol vs
Metoprolol on Mortality
Poole-Wilson PA et al. Lancet. 2003;362:7–13.
17%
Risk reduction

COMET: Median Survival
Carvedilol 8.0 years
Metoprolol 6.6 years
Carvedilol prolonged median survival by 1.4
years beyond that achieved with metoprolol
Assuming constant hazard
Poole-Wilson PA et al. Lancet. 2003;362:7–13.

Spironolactone and Epelnerone
ALDOSTERONE RECEPTORS WITHIN
THE HEART MEDIATE
FIBROSIS, HYPERTROPHY AND
ARRHYTHMOGENESIS
 REDUCTION IN ALL CAUSE
MORTALITY AND SYMPTOMATIC
RELIEF IN PATIENTS WITH
ADVANCED CHF AT DOSES
25MGM/DAY

Spironolactone and Epelnerone
 HYPERKALAEMIA,PARTICULARLY WHEN
USED WITH ACE-INHIBITORS/ATRAs
 IN PATIENTS WITH IMPAIRED RENAL
FUNCTION.MONITORING OF POTASSIUM
LEVELS ESSENTIAL
 USED IN COMBINATION WITH
ACEINHIBITOR,LOOP DIURETIC +/-
DIGOXIN

Digoxin
 BLOCKAGE OF THE SODIUMPOTASSIUM
ATPase PUMP RESULTS IN INCREASED
INOTROPIC RESPONSIVENESS
 THE DATA SUGGESTS THAT DIGOXIN HAS
NO INFLUENCE ON SURVIVAL BUT
REDUCES HOSPITALISATION AND
IMPROVED THE QUALITY OF LIFE OF
MANY PATIENTS

Heart Failure-Medical Treatment
 Digoxin improves Symptoms and
prevents hospitalizations in men but
not women.
 Niseritide (Natracor) induces diuresis
and improves symptoms but does
not improve longevity
 Amiodarone helps prevent arrythmic
events

Heart Failure Device Treatment
 Bi-Ventricular pacemaker helps
improve cardiac output and improves
symptoms sometimes.
 Automatic Implantable Defibrillator
improves survival in patients with EF
less than 35%. (Better than drug
therapy alone)

COMPANION: Secondary End
Point of All-cause Mortality
Bristow MR et al. Paper presented at American College of Cardiology. March 31, 2003; Chicago, Ill.
12-month
OPT Event Rate
(1-y) = 19.0%
P=.12, CRT vs OPT
P=.002, CRT-D vs OPT
12-month event rate reductions:
CRT = by 23.9%
CRT-D = by 43.4%
Any Death
%PatientsEvent-Free
Days from Randomization
0 120 240 360 480 600 720 840 960 1080
60
50
70
80
90
100
CRT = cardiac resynchronization therapy. CRT-D = cardiac resynchronization therapy plus implantable
cardioverter defibrillator. OPT = optimal drug therapy.
CRT-D
OPT
CRT

REMATCH-LVADs in Extremely Severe Heart
Failure
100
80
60
40
20
0
0000 6 12 18 24 30
No. at Risk
LV assist device
Medical therapy
68 18 22 11 5 1
61 27 11 4 3 0
Months
Survival(%)
Medical therapy
LV assist device
Rose EA. N Engl J Med. 2001;345:1435–1443.

People Don’t want and LVAD,
they want a Heart

Heart Transplant Waiting List
January 9th 2012
73 people Washington
DC metropolitan area
waiting for heart
transplant
3155 people In USA
waiting for heart
Transplant
2011, 1,760 patients on the heart
wait list received heart
transplants. That figure
represents a decrease from the
2,333 hearts transplanted in 2010
and the 2,211 in 2009.

Heart Transplantation
 There were 2,125 heart transplants performed in
the United States in 2005 and 2,016 in 2004.
 Each year thousands more adults would benefit
from a heart transplant if more donated hearts
were available.
 In the United States, 72.4 percent of heart
transplant patients are male; 70.0 percent are
white; 19.1 percent are ages 35-49 and 45.0
percent are ages 50-64.
 As of Aug. 11, 2006,the one-year survival rate
was 86.1 percent for males and 83.9 percent for
females; the three-year survival rate was
about 78.3 percent for males and 74.9 percent
for females. The five-year survival rate was 71.2
percent for males and 66.9 percent for females.

Markers of Heart Failure
 Identify Markers and we can better
treat the disease
 Albumin
 BNP
 Chest to HEART MIBG ratio- a marker for denervation of
the heart and loss of sympathic tone- assessment of
myocardial sympathetic innervation, as determined by the heart to
mediastinum (H/M) ratio on planar 123I-mIBG imaging as either
normal (>1.6) or abnormal (<1.6), for identifying HF subjects at
higher risk of experiencing an adverse cardiac event.

UACR= urinary albumin to creatinine ratio. Macroalbuminuria=UACR >25 mg/mmol.
Microalbuminuria=UACR 2.5–25.0 mg/mmol (men) or 3.5–25.0 mg/mmol (women).
*compared with normoalbuminuria (UACR<2.5 mg/mmol), n=1349
End point Microalbuminuria,
n=704*
Macroalbuminuria,
n=257*
Per 100-
mg/mmol
UACR
increment
CV death or HF
hospitalization
1.43 (1.21–1.69) 1.75 (1.39–2.20) 1.07
(1.00–1.14)
All-cause
mortality
1.62 (1.32–1.99) 1.76 (1.32–2·35) 1.08
(1.00–1.17)
HF
hospitalization
1.31 (1.07–1.59) 1.67 (1.28–2·17) 1.07
0.99–1.15)
Albumin excretion is prognostic marker in heart failure
(Analysis from CHARM Study)
Adjusted hazard ratios (95% CI) for clinical outcomes by degree of albuminuria (defined
by UACR with cut points and as continuous variable) in CHARM
Jackson CE et al. Lancet 2009; 374:543–550.

All-cause Mortality vs BNP (Median 140)
Survival
Probability
Time (days)
<Media
n*
Less
than
140
BNP
>Median
Greater
Than 140
BNP
*p<0.00001

H/M=0.96
Died at 8 mo
HF Progression
H/M=1.38
Died at 8 mo, SCD
(No ICD)
H/M=1.67
No event
1 2
Three Patients with NYHA Class II HF and LVEF
between 20 and 25%. Patient 1 has highly
elevated BNP (>1000). BNP in patients 2 and 3 is
normal (<100).
Based upon the results of ADMIRE-HF, 2-year cardiac
mortality risk for patient 1 is 10 times that of patient 3.
(IF your Chest to HEART MIBG ratio is greater than 1.6 you don’t die)

All-cause Mortality vs BNP (Median 140) & H/M
Time (days)
BNP>140
& H/M ≥1.60
BNP>140
& H/M<1.60*
BNP<140
& H/M<1.60
BNP<140
& H/M ≥1.60
Survival
Probability
*p=0.024 vs BNP>140 & H/M
≥1.60

Current and Future Therapies
 Drugs
 CHF disease
management
programs
 Resynchronizatin
therapy + ICD
 Renal
Denervation
 ultrafiltration does not
work if diuretic
resistant
 LVADs
• Total artificial heart
 Cardiac transplant
• (batista,cardiomyoplast
y & ―acorn‖ does not
work)
Early-stage Treatment Late-stage Treatment
Resynchronization therapy is an effective
early-stage therapy

Curing Heart failure by curing
hypertension- Denervating the
Kidney

Stem Cells trial Shows Promise
for Ischemic heart failure.
 -11/6/2012 AHA Encouraging two-year follow-up from the Stem
Cell Infusion in Patients with Ischemic
Cardiomyopathy (SCIPIO) trial
 -c-KIT-positive Ccardiac stem Cells in patients with left ventricular
dysfunction (LVEF <40%) following an MI. In the trial, the cells
were harvested from the patient's right atrial appendage, isolated
and expanded, and then infused to repair an infarction during
coronary bypass surgery.
 -Echocardiography showed the average LVEF in the 18 patients
treated with the CSC infusion increased from 29.0% before
infusion to 36.0% (p <0.001) four months after the procedure.
During that period, LVEF improved only from 29.2% to 29.4% in
13 control patients.

Balloon Pump to augment
Coronary Perfusion

EECP
 Reduced frequency or complete elimination
of angina symptoms.
 Better ability to exercise free from chest pain and
breathlessness.
 Decrease in need for anti-angina nitrate
medication
 Clinical tests show:
 Decreased exercise-induced signs of angina on
ECG (prolonged time to ST depression on exercise
stress testing)
 Increased blood supply to heart muscle ,
demonstrated by myocardial perfusion scan
techniques before and after EECP (Technetium
scan, Cardiovascular MRI, stress ECHO)
 Improvement of EF in some Patients.

Future Horizons and Pipe Dreams
 Heart Transplantation- A viable
option for a select few patients.
 Left Ventricular Assist devices and
the Artificial heart, are available
options and used mainly as a bridge
to transplant and not destination
therapy.
 Stem cell transplantation and
myocaridal cell imlantation have not
yet proven viable.

Worldwide REGISTRY DATABASE:
Number of Transplants Reported
ORGAN
Transplants Reported
from 7/1/2006 through
6/30/2007
Total Transplants
Reported through
6/30/2007
Heart 3,114 80,106
Heart-Lung 63 3,341
Lung 2,099 25,950
ISHLT 2008
J Heart Lung Transplant 2008;27: 937-983

The HeartMateII is a continuous flow cardiac assist device. Heart surgeon
"Bud" Frazier and his team are working with two such devices to develop
a continuous flow artificial heart. (Courtesy: Texas Heart® Institute)
Artificial Heart

Evidence-Based Treatment Across the
Continuum of Systolic LVD and HF
Control Volume Improve Clinical Outcomes
Diuretics
Renal Replacement
Therapy*
Digoxin
-BlockerACEI
or ARB
Aldosterone
Antagonist
or ARB
Treat Residual Symptoms
CRT
an ICD*
HDZN/ISDN*
*In selected patients

Drugs to avoid in heart failure
 NSAID – I buprophen( Advil, Motrin),
Naproxen ( Alieve, Naprosyn). Cox-2
inhibitors (Celebrex)
 The NSAID can cause kidney to
retain salt and water, and Interfere
with ACE/ARB class
 Use Acetemenphen Or Narcotics
instead for pain and aches.

Drugs to Avoid in CHF
 Anti-Arrhythmics in Class 1 ( Sodium
Blockers and Class 3 ( Potassium
Channel blockers)
 The only heart rhythm drugs safe in
Systolic dysfuction are Amiodarone
and Dofeditilide (Tikosyn)

Drugs to Avoid in CHF
 Avoid Non Dihydropyridine Calcium
Channel blockers.
 Non- dihydropridine Calcium Channel
blockers (Verapamil & Diltiazem)
decrease the strength of myocardial
contractility and decrease heart rate.
 Verapamil and Diltiazem can worsen
Heart failure and do not improve
survival.

1,5 Dihydropiridines are neutral in
Heart failure as Anti-hypertensives
 Amlodipine and Felodipine have not
been shown to decrease survival in
heart failure.

Kaplan–Meier Plots of the Time to the First Primary Event (Death or
Cardiovascular Morbidity) among 571 Patients with Chronic Heart Failure
Receiving Amlodipine and 582 Receiving Placebo.
Packer M et al. N Engl J Med 1996;335:1107-1114.

Drugs to Avoid In CHF
 Antacids that contain sodium (salt): To relieve heartburn or
indigestion.
 Why: Just like eating salty foods, sodium from medications can
cause your body to retain fluid, making swelling and shortness of
breath worse and raising blood pressure.
 Alternatives: Some companies produce low-sodium antacids.
Look at the ingredients list and warning statements to see if
sodium is listed (companies are required to put it on the label if
there are 5 mg or more of sodium per dose). If you are not sure,
ask your doctor or pharmacist.
 Other Drugs to Avoid
 Decongestants containing pseudoephedrine (such as Sudafed),
which can raise blood pressure and force the heart to work harder
 Alcohol and illicit drugs; they are a common cause of
hospitalization for heart failure
 Some nutritional supplements and growth hormone therapies (talk
to your doctor about any you are considering taking)

Other drugs to Avoid in Heart
failure
 Pain relievers called NSAIDs
 Ibuprofen, such as Advil and Motrin
 Naproxen, such as Aleve
 Aspirin, such as Bayer
• If your doctor has told you to take a low-dose aspirin every day for your heart
problems, it's probably okay to take it. Low-dose aspirin can help prevent blood clots
and may prevent a stroke or a heart attack.
• Higher doses of aspirin may make your heart failure worse. Do not take aspirin for
pain, such as from headaches or arthritis. Use acetaminophen, such as Tylenol,
instead.
 Pain relievers
 Celecoxib
 Etodolac
 Indomethacin
 Ibuprofen
 Ketoprofen
 Nabumetone
 Naproxen
 Piroxicam
 Sulindac

Drugs to Avoid in heart failure
 Cold, cough, flu, or sinus medicines
 Be sure to check the label. Do not take medicines that contain
pseudoephedrine, ephedrine, phenylephrine, or oxymetazoline, such as:
• Sudafed.
• Nose sprays (decongestants), such as Afrin and Dristan.
• Herbal remedies, such as ma huang and Herbalife.
 Make sure your cough and cold medicines don't contain aspirin or ibuprofen.
 Antiarrhythmics
 These are drugs used to treat a fast or uneven heart rhythm. You may need to
avoid the following:
• Disopyramide
• Dofetilide
• Flecainide
• Procainamide
• Propafenone
• Quinidine
• Sotalol

Drugs not to take with Heart
failure
 Antacids or laxatives that contain sodium
 Check the label for sodium or saline. Examples include:
• Antacids, such as Alka-Seltzer.
• Laxatives, such as Fleet Phospho-Soda.
 Calcium channel blockers
 People with a certain kind of heart failure may need to avoid the
following medicines:
• Diltiazem
• Verapamil
 If you need to take a calcium channel blocker for another health
problem, such as high blood pressure, your doctor will watch your
health carefully.
 Certain diabetes medicines
 Most diabetes drugs are safe to take, but you may need to avoid
the following:
• Metformin
• Rosiglitazone and pioglitazone1 ( Avandaia and ACTOS)

Biggest Myth: Vitamins prevent
CVD risk or heart failure risk.
 The largest, randomized, double-blind trial to date has confirmed
what smaller studies have suggested and what many physicians
have long believed: a daily multivitamin does not reduce the risk
of CVD
 Physcians Health Study II results presented at AHA Nov 2012
 PHS II launched in 1997, with a total of 14 641 US male
physicians, age 50 or older at the outset, randomized to different
vitamin arms or placebo. The other three arms of the study—
looking at beta-carotene, vitamin E, or vitamin C
 Over a median follow-up of 11.2 years, 1732 CV events occurred,
but the rate of events was no higher among men taking placebo
than those taking a daily multivitamin

Ultrafiltration- doesn’t work
 11/4/2012 AHA meeting- Ultrafiltration was associated with
worsening renal function and more severe adverse events
compared with optimum drug therapy in patients with acute
decompensated heart failure in the CARRESS-HF trial
 CARRESS-HF trial involved 188 patients with acute
decompensated heart failure with worsening renal failure who
were randomized to stepped pharmacological care or
ultrafiltration. The primary end point was change in serum
creatinine and change in weight (reflecting fluid offload) at 96
hours
 -similar weight loss occurred in both groups (average about
12 pounds), but while there was little change in creatinine
levels in the drug-treated group, there was a significant
increase in creatinine in the ultrafiltration group. There was no
difference between the two groups in death or hospitalization
for heart failure, but there were more severe adverse events
in the ultrafiltration group (72% vs 57%), mainly due to
kidney failure, Bleeding and and IV-catheter-related
complications.

What doesn’t Help
Aliskarin for dual ARB-Renin Blocade
 November 3, 2012 in the New England Journal of Medicine.
 Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal
Endpoints (ALTITUDE) trial, testing Aliskiren (Tekturna, Novartis
Pharmaceuticals) as an adjunct to renin-angiotensin-aldosterone
system (RAAS) blockade.
 The drug not only failed to provide benefit to patients with type 2
diabetes at high risk of CV and renal events but may actually have
been harmful .
 In ALTITUDE, 8561 patients were randomly assigned to aliskiren
(n=4274) or placebo (n=4287) on a background of an ACE inhibitor
or ARB for approximately four years.
 The primary end point was a composite of CV death, resuscitation
from sudden death, nonfatal MI or stroke, unplanned hospitalization
for heart failure, ESRD or renal death, or a doubling of serum
creatinine for at least one month.
 There was no statistical difference in the primary end point between
the treatment groups, but the aliskiren group experienced more
adverse events, especially hyperkalemia and hypertension.

Neseritide- Doesn’t make a
difference
 ACC- 2010 - Acute Study of
Clinical Effectiveness of
Nesiritide in Decompensated
Heart Failure(ASCEND-HF), there
was "no evidence for a major
benefit" from nesiritide vs placebo
on top of standard care.

Primary results and renal-function safety end point in
ASCEND-HF, IV nesiritide in ADHF
ASCEND-HF-
End points Placebo (%), n=3511 Nesiritide (%), n=3496 p
30-d death/HF hospitalization* 10.1 9.4 0.31
•30-d death 4.0 3.6
•30-d HF rehospitalization 6.1 6.0
Dyspnea at 6 h* 42.1 44.5 0.030
•Moderately better 28.7 29.5
•Markedly better 13.4 15.0
Dyspnea at 24 h* 66.1 68.2 0.007
•Moderately better 38.6 37.8
•Markedly better 27.5 30.4
>25% decrease eGFR 29.5 31.4 0.11
a. *Co–primary end points
eGFR=estimated glomerular filtration
rate
Acute Study of Clinical Effectiveness of
Nesiritide in Decompensated Heart
Failure 11/4/2010 American Heart
Association

HFSA 2010 Practice Guideline (3.2)
HF Risk Factor Treatment
Goals
Risk Factor Goal
Hypertension Generally < 130/80
Diabetes See ADA guidelines1
Hyperlipidemia See NCEP guidelines2
Inactivity 20-30 min. aerobic 3-5 x wk.
Obesity Weight reduction < 30 BMI
Alcohol Men ≤ 2 drinks/day, women ≤ 1
Smoking Cessation
Dietary Sodium Maximum 2-3 g/day
1Diabetes Care 2006; 29: S4-S42
2JAMA 2001; 285:2486-97
Adapted from:

Common precursors of chronic
heart failure
 •Coronary artery disease (for example, consequent
 upon acute myocardial infarction)
 •Chronic hypertension
 •Cardiomyopathy (for example, dilated,
 hypertrophic, alcoholic, and idiopathic)
 •Valve dysfunction (for example, diseases of the
 aortic and mitral valve)
 •Cardiac arrhythmias/conduction disturbance (for
 example, heart block and atrial fibrillation)
 •Pericardial disease (for example, constrictive
 pericarditis)
 •Infection (for example, rheumatic fever, Chagas
 disease, viral myocarditis, and HIV

History of Beta Blockade for CHF
 1993, The Metoprolol in Dilated
Cardiomyopathy Trial studied 383 patients
with class 2-3 CHF for 18 months. The
target dose of immediate-release
metoprolol was 100 to 150mg per day.
The metoprolol group showed reduced all-
cause mortality compared to the placebo
group, but the difference was small.
 The major benefit was in need for heart
transplant. Two metoprolol patients
needed a heart transplant but 19 in the
placebo group did. Metoprolol improved
EF, quality of life, and exercise capacity
compared to placebo

USING BETA BLOCKERS IN PATIENTS
WITH COMORBIDITIES
 􀂄 AFTER MI-USE IN ALL PATIENTS WITHOUT A
 CONTRAINDICATION
 􀂄 COPD IS NOT A CONTRAINDICATION
 UNLESS THERE IS SEVERE REACTIVE
 AIRWAYS DISEASE
 􀂄 PERIPHERAL VASCULAR DISEASE-USE
 LOWER DOSES OF METOPROLOL OR
 BISOPROLOL
 􀂄 DIABETIC PATIENTS DERIVE SIGNIFICANT
 BENEFIT-CARVEDILOL MAY BE PREFERRED

Digoxin
 􀂄 BLOOD LEVEL MONITORING REQUIRED
 􀂄 LEVELS FOR HEART FAILURE ARE USUALLY
 0.5-0.8NG/Ml FOR HEART FAILURE AND UP
 TO 2NG/ML FOR ATRIAL FIBRILLATION
 􀂄 DOSE DEPENDS ON DEGREE OF RENAL
 FUNCTION.
 􀂄 LOADING DOSES REQUIRED FOR MORE
 RAPID RESPONSE
 􀂄 MONITOR FOR NAUSEA AND VOMITING
 WHICH ARE OFTEN EARLY SIGNS OF
 TOXICITY

Treatment of Diastolic CHF
 APART FROM A FEW EXCEPTIONS
DATA FROM LONG TERM
INVESTIGATIONS OF ANY AGENT
COMPARED TO PLACEBO IN
PATIENTS WITH DIASTOLIC FAILURE
ARE LACKING

Diastolic CHF
 REDUCTION IN LFT VENTRICULAR FILLING
PRESSURES WITH THE USE OF DIURETICS
AND/OR NITRATES
 SLOWING OF THE HEART RATE WITH
BETABLOCKERS AND /OR RATE LIMITING
CALCIUM CHANNEL BLOCKERS SUCH AS
VERAPAMIL (WHICH IS GENERALLY
CONTRAINDICATED IN SYSTOLIC
FAILURE)

Diastolic CHF
 RECENT STUDY WITH CANDERSARTAN
IN PATIENTS WITH LVEF>40%
DEMONSTRATED A SIGNIFICANT
REDUCTION IN HOSPITALISATIONS
FOR HEART FAILURE. THERE WAS NO
SIGNIFIACNT DIFFERENCE IN THE RISK
OF STROKES OR MYOCARDIAL
INFARCTION

Predictors of Mortality Based on
Analysis of ADHERE Database
 Classification and Regression Tree (CART) analysis of
ADHERE data shows:
 Three variables are the strongest predictors of
mortality in hospitalized ADHF patients:
BUN > 43 mg/dL
Systolic blood pressure < 115 mmHg
Serum creatinine > 2.75 mg/dL
Fonarow GC et al. JAMA 2005;293:572-80

Heart failure update 2012

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Heart failure update 2012