Optimizing Heart
Failure Management
2005
Bridging the CARE GAP
CME Needs of Family
Physicians re CHF
•
•
•
•
Early detection
Etiology
Prognosis
Diagnosis
– Physical exam
– Asymptomatic LV
dysfunction
• How to use beta blockers
– Which beta blocker
– Better standardization of
therapy
• Rx titration
– Diuretics
– Beta blockers
• Post hospital
interventions
– Lifestyle
– Patient education
• Diet
• Rx
• Exercise Rx
• Compliance
• Multi-system disease
– Renal disease
Measuring the Impact of HF
•
•
•
•
•
Currently, there are over 500,000 Canadians
with HF
Incidence 50,000 cases/year
One year mortality after diagnosis ranges
between 25-40% (ICES Atlas)
1% of Canadians over age 65 and 4% of
Canadians over 70 have CHF
The age-adjusted mortality for CHF is
106/100,000
Measuring the Impact of HF
• Median survival currently 1.7 years for males, 3.2
yrs for females
• 5-year age adjusted mortality rate of 45% based on
the time period 1990-1999
• Commonest diagnosis that brings a patient to
hospital for medical admission.
• Re-admission rates are 46% within 3 months of
discharge and 54% within 6 months.
Heart Failure Epidemiology
• Heart failure associated with high morbidity and
mortality
• Contemporary Canadian data to quantify the
burden of CHF is limited
• In 2000/01:
–
–
–
–
–
Total of 106,130 discharges for 85,679 CHF patients
32.7% of discharges were readmissions
19.9% of patients were re-hospitalized once or more during 2000
Total in-hospital mortality was 15.8%.
CHF is associated with the second highest total number of hospital
days and third highest number of patients affected.
Can J Cardiol. 2003 Mar 31;19(4):436-8.
Contemporary burden of illness of congestive heart failure in Canada.
Tsuyuki RT, Shibata MC, Nilsson C, Hervas-Malo M.
Contemporary burden of illness of congestive heart
failure in Canada.
Tsuyuki RT, Shibata MC, Nilsson C, Hervas-Malo M.
“These figures should signal a call to
action for researchers,
administrators and health care
providers regarding the need for
more efficacious therapies, better
application of already-proven
therapies and patient education.”
Can J Cardiol. 2003 Mar 31;19(4):436-8.
Heart Failure is the Quintessential
Disorder of Cardiovascular Aging
• Convergence of
– Age related changes in cardiovascular
structure and function
• Rising prevalence of
– Hypertension
– Coronary heart disease
– Valvular heart disease
Chronic Congestive Heart Failure
Evolution of Clinical Stages
NORMAL
Asymptomatic
LV Dysfunction
No symptoms
Compensated
Normal exercise
CHF
Abnormal LV fxn
No symptoms
Decompensated
Exercise
CHF
Abnormal LV fxn
Symptoms
Refractory
Exercise
CHF
Abnormal LV fxn
No symptoms
Normal exercise
Normal LV fxn
Symptoms not controlled
with treatment
Ventricular Remodeling in CHF
Jessup, NEJM 2003
Symptoms of HF
•
•
•
•
•
Fatigue
Activity decrease
Cough (especially supine)
Edema
Shortness of breath
DIET Approach to the Patient
With Heart Failure
• Diagnose
– Etiology
– Severity (LV
dysfunction)
• Initiate
–
–
–
–
Diuretic/ACE inhibitor
-blocker
Spirololactone
Digoxin
• Educate
–
–
–
–
Diet
Exercise
Lifestyle
CV Risk
• Titrate
– Optimize ACE
inhibitor
– Optimize -blocker
Therapy of CHF
Clinical Approach to CHF:
Consider etiology
Identify triggers
Exclude ischaemia
General measures
Symptomatic therapy
Prognostic therapy
See Guide for HF Management Check-list
Guide for HF Management

Approach
Recommendations
Symptoms &
Signs of HF:
Fatigue (low cardiac output), SOB, JVP, rales, S3, edema, radiologic congestion,
cardiomegaly. Elevated BNP. CXR to r/o infection, interstitial lung disease & PPH
Ejection fraction
(obtain echo or
LV gated study)
 40% = systolic dysfunction
40-55% = mixed systolic and diastolic dysfunction
 55% = diastolic dysfunction - treat underlying disorder (HPT/ischaemia/pericardial
constriction/restrictive CM (cardiomyopathy)/infiltrative disorders)
 Ischemic-CM HPT-CM  Valvular HD-CM (AS/AR/MR)  Metabolic:
hyper/hypo thyroidism / hemochromatosis/pheochromocytoma  Toxins: Alcohol/
anthracyclines/cocaine/amphetamines Viral CM Idiopathic Dilated CM  Other:
Consider etiology
Identify triggers
Acute-sudden onset
Chronic-gradual onset
Treatment:
General measures
Symptomatic therapy
Therapy to
improve prognosis
Consider ACE-I/ARB
combination in ACE-I
and /or -blocked
patients with worsening
HF or hospitalization
Caution:diabetics/renal
disease/elderly/ NSAIDs
& COX-2 inhibitors
Anti-coagulant
anti-platelet Rx
Ischaemia, arrhythmia, infection, pulmonary embolism, acute valvular pathology
Anemia, thyrotoxicosis, non-compliance, diet, Rx e.g. NSAID’s
Correct triggers and precipitants of acute and chronic Heart Failure
 Low sodium diet
 D/C smoking
 Regular exercise/activity
 Treat lipid abnormalities
 Treat ischemia
 Treat and control diabetes
 Control hypertension
 Identify & Rx depression
Diuretics-titrate to euvolemic state
 Maintain Ideal Body Weight (dry weight = JVP normal / trace pedal edema)
 Furosemide 20 - 80 mg OD-BID
 HCT/Zaroxolyn for refractory congestion
Digoxin-for persisting symptoms in NSR (systolic dysfunction) or symptoms and rate
control in Afib. Dose: 0.125 mg – 0.25 mg (Lower dose in elderly: 0.0625 mg)
ACE Inhibitors-General Guideline:
 Trandolapril 1  4 mg mg OD‡
Start low and titrate to the target dose
 *Quinapril 10 mg  40 mg OD
used in the clinical trials or the
 *Cilazapril 0.5 mg  10 mg OD
MAXIMUM TOLERATED DOSE:
 *Fosinopril 5 mg  40 mg OD
 Captopril 6.25-12.5 mg 
 *Perindopril 4 mg  8 mg OD
50 mg BID-TID
*No large scale outcome trials
 Enalapril 2.5mg 10mg BID†
† SoLVD/X-SoLVD § AIRE /AIREX‡TRACE
 Ramipril 2.5 mg  5mg BID §
Consider ISDN 5-40mg QID+Hydralazine 10 Lisinopril 2.5 mg 30-40 mg OD 75mg QID for ACE-I/ARB intolerance VHeFT
Angiotensin II receptor antagonists (ARB’s)
 ACE-Inhibitors remain first line therapy
 ARB’s indicated in ACE-I intolerant patients
 (CHARM candesartan 16-32 mg OD) (Val-HeFT /VALIANT valsartan 160 mg BID)
Beta-blockers-Add Beta-blocker* to ACE-inhibitor/diuretic/+/- digoxin in stable Class
II-IV CHF/LVEF  40% (*No outcome data for other beta-blockers)
 Bisoprolol* 1.25  10 mg OD (CIBIS II Trial)
 Carvedilol* 3.125 mg BID  25 mg BID (50 mg BID if weight > 85 kg)
 Metoprolol* 12.5 mg BID  75 mg BID (MERIT Trial)
Aldosterone antagonist (follow K/Cr in 3-7 days/ furosemide to avoid azotemia)
 Spironolactone 12.5-25 mg OD added to ACE-inhibitor/diuretic/+/- digoxin in stable
Class III-IV CHF/LVEF  35%/CR<220/K<5.0 (RALES Trial)
ASA if CAD ( dose to  ACE inhibitor interaction)
Coumadin for Afib, LV thrombus,  LVEF  20%, DVT or pulmonary embolism
Duration of A/C therapy: Indefinite for Afib/recurring systemic TE or DVT/PE
Consider Internal Medicine/Cardiology or Heart Failure Clinic referral for initiation/titration of - blocker. Consider EPS
referral for symptomatic sustained or non-sustained ventricular arrhythmia (LVEF 30-40%) or AICD: Prior MI/CAD (LVEF 
30% with IVCD  0.12 sec: MADIT II) CHF: (NYHA II-III & LVEF <35% SCD-HeFT) Cardiac Resynchronization
Therapy(CRT):(NYHA Class III-IV with reduced ejection fractions; LVEF < 35%; QRS duration  0.13 with IVCD or LBBB:
MIRACLE / MUSTIC) or both CRT/AICD: (NYHA III-IV;QRS  0.12:COMPANION). EECP/Transplant for refractory CHF.
Symptoms & Signs of HF:
•
•
•
•
•
•
•
•
Fatigue (low cardiac out-put)
SOB
 JVP
Rales
S3
Edema
Radiologic congestion
Cardiomegaly
Obtain CXR to r/o non-cardiac causes e.g. interstitial lung
disease & PPH
BNP in the Diagnosis of HF
The role of natriuretic peptides
• ANP-atrial natriuretic peptide
– Produced in atria in response to wall stress
• BNP-brain natriuretic peptides
– Produced in ventricles in response to volume and pressure
overload
• CNP-central nervous system and endothelium
– Produced in response to endothelial stress
• Produced as prohormones and cleaved to active molecule
(ANP/BNP)and inactive NT forms
BNP in the Diagnosis of HF
ANP/BNP elevated in
•
•
•
•
•
•
•
•
Heart failure
Systemic and pulmonary hypertension
Hypertrophic and restrictive cardiomyopathy
Pulmonary embolism
COPD
Cor pulmonale
AMI Cirrhosis
Renal Failure
BNP in the Diagnosis of HF
Higher levels of BNP correlate with
• higher PCW pressures
– in compensated and decompensated patients
• larger LV volumes
• lower ejection fractions
– in symptomatic HF patients
• BNP study (Circ 2002;106: 416-422)
– BNP sensitivity 90% and specificity 73% for HF
BNP Diagnostic Cut Points for CHF
JACC 2001;37(2):379-85.
BNP > 400 pg/L – acute CHF present
BNP 100 pg/L – 400 pg/L
• Diagnostic of CHF with
–
–
–
–
Sensitivity 90%
Specificity 76%
Predictive accuracy 83%
R/O pulmonary embolism, LV dysfunction without
acute CHF or cor pulmonale
BNP < 100 pg/L – 98% negative predictive accuracy
Identify triggers
Acute-sudden onset
• Ischaemia
• Arrhythmia
• Infection
• Pulmonary
embolism
• Acute valvular
pathology
Chronic-gradual onset
• Anemia
• Thyrotoxicosis
• Non-compliance
• Diet
• Rx e.g. NSAID’s
Non-Invasive Evaluation of the Heart Failure
Patient-Implications of LV Ejection Fraction
• To know where you
are going you must
know where you are
coming from
• Evaluate LV function
 clinical
 echo
 gated study
Ejection fraction
(obtain echo or LV gated study)
• LVEF  40% = systolic dysfunction
• LVEF 40-55% = mixed systolic and
diastolic dysfunction
• LVEF  55% = diastolic dysfunction
 identify triggers
– treat underlying disorder
(HPT/ischaemia/pericardial
constriction/restrictive CM/infiltrative
disorders)
Echocardiographic Evaluation
of CHF
• LV function (EF),chamber
size,wall motion
• Segmental dysfunctioncoronary disease
• MS-severity, valve area
• AS- valve gradient, valve
area
• AR/MR severity
• TR- RV systolic pressure
= PA pressure
•
•
•
•
RV function
R/O IHSS, HCM
R/O Pericardial Disease
R/O rare causes e.g.
myxoma, infiltrative
disorders- restrictive
cardiomyopathy
• Diastolic function
• Hyperdynamic states
Diastolic Dysfunction
• 30-50% of elderly HF patients have
reserved LV systolic function
• Diastolic dysfunction may induce dyspnea
on exertion
• Frank congestion usually has identifiable
precipitant
Clinical Implications of LV
Dysfunction in Heart Failure
• Calculated EF by echo
unreliable in remodeled
LV
• Visual estimate of EF
semi-quantitative
• (CCN LV function scale)
–
–
–
–
Grade I LV EF ≥50%
Grade 2 LVEF 35-49%
Grade 3 LVEF 20-34%
Grade 4 LVEF< 20%
LVEF Entry Criteria in ACE
inhibitor and
-blocker Trials
– SOLVD treatment an
prevention  35%
– SAVE (post MI)  40%
– U.S. Carvedilol HF Trials
Program LVEF  35%
– Merit-HF LVEF  40%
– CIBIS II LVEF  40%
Consider etiology
•
•
•
•
Ischemic- Cardiomyopathy (CM)
HPT-CM
Valvular HD-CM (AS/AR/MR)
Metabolic:
 / thyroid/hemochromatosis/
pheochromocytoma
• Toxins:
 Anthracyclines/Etoh/cocaine/amphetamines
• Viral CM
• Idiopathic Dilated CM
• Other:
Treatment
General Measures
General measures:
• Correct triggers and
precipitants of acute
and chronic HF
• Low sodium diet
• Fluid restriction
• Regular exercise/
• Activity HR Rx
•
•
•
•
Treat ischemia
Control hypertension
D/C Smoking
Treat lipid
abnormalities
• Treat and control
diabetes
• Identify & Rx
depression
HF Management Algorithm
Is it Heart Failure?
Symptoms & Signs
YES
Diagnostic Tests:
CXR/ECG/±BNP
Additional Tests
±Specific Tx
•Cath
•CABG
•Valve Sx
YES
Echo/RNA/MRI:
Etiology/Severity
Systolic HF:
Medical±Sx/Device
Life Style +
Patient Education
± HF Clinics F/U
Diastolic HF:
Rx cause±Referral
Primary Targets of Treatments
in CHF
Jessup, NEJM 2003
Symptoms
Prognosis & Symptoms
Assess LV Function (echo, gated RNA)
•EF < 40%-systolic dysfunction
•EF 40-55%-systolic/diastolic dysfunction
•EF >55%-diastolic dysfunction
Assess Volume Status
Signs and Symptoms of
Fluid Retention
Loop Diuretic
+/- Thiazide
(titrate to euvolemic state)
Add Digoxin for
symptom control
No Signs and Symptoms
of Fluid Retention
ACE inhibitor/ARB if ACE intolerant
Combination Rx if  HF, hospitalization or -blocker intolerant
-blocker (NYHA II-IV)
Spironolactone
(NYHA Class III-IV CHF/EF<35%/Cr<200/K<5)
Heart Failure Therapeutic Goal
• Mild-Moderate Heart Failure
– Primary goal = Reduce mortality
– -blockers + ACE inhibitors
– Prevent progression to symptoms
– Prevent progressive LV dysfunction
Heart Failure Therapeutic Goal
• Moderate-Severe Heart Failure
– Primary goal = Reduce symptoms
– Improve quality of life (QOL)
– Reduce hospitalizations
– Prevent sudden death
General Rx Strategies in HF
Asymptomatic
Mild/Mod
Severe
Refractory
Inotropes, mitral repair, VAD, Tx
Correct Cause:
Arrhythmias
Ischemia
Pressure Load
Tailored Rx
Digoxin
Diuretics (Spironolactone)
Carvedilol/ -Blockers
Angiotensin Converting Enzyme Inhibitors
No Added Salt
Activity as Tolerated
Modified from Warner-Stevenson, ACC HF Summit
2 gm Na
Customized Ex Training
Symptomatic therapy
Diuretics (see How to Adjust Your Diuretic)
• Titrate to euvolemic state
• Maintain Ideal Body Weight
– (dry weight = JVP normal / trace pedal edema)
• Furosemide 20 mg. – 80 mg OD-BID
• HCT/Zaroxolyn for refractory congestion
Digoxin
• For persisting symptoms in NSR (systolic
dysfunction)
• or symptoms and rate control in Afib.
 Dose: 0.125 mg – 0.25 mg
 (Lower dose in elderly: 0.0625 mg)
The Effect of Digoxin on Mortality and
Morbidity in Patients with Heart Failure
1
Digitalis
Investigation
Group (DIG Trial)
- a large simple, long-term trial
Sponsored by the National Heart, Lung, and Blood Institute
and Department of Veterans Affairs
Cooperative Studies Program
NEJM Volume 336:525-533 February 20, 1997 Number 8
DIG Trial
13
DIG: All Cause Deaths
50
50
40
40
Percent Event
Percent Mortality
15
DIG: CHF Mortality or
Related Hospitalizations
30
20
Placebo
p = 0.80
10
Digoxin
30
Placebo
20
10
Digoxin
0
0
4
8
12
16
20
24
28
Months
32
36
40
44
48
p = 0.0001
52
0
0
4
8
12
16
20
24
28
Months
32
36
40
44
48
52
DIG Trial
16
DIG: CHF Mortality or Related Hospitalizations
Harm
Benefit
EF
Prev Dig Use
CT Ratio
< 0.55
> 0.55
NYHA Class
• Reduced worsening heart
failure deaths
Yes
No
IHD
Non-IHD
• Reduced worsening heart
failure hospitalizations
I/II
III/IV
Overall
0.25
DIG: Conclusions
• No effect on overall survival
25 -45
< 25
Etiology
20
0.5
0.75
(Risk Ratio: Active/Control)
1
1.25
• Small absolute excess in
digoxin toxicity
ACE Inhibitors are the Cornerstone
of Rx in CHF
CCS 2003 Consensus HF Update (draft)
• ACE I Rx ASAP post MI
– Continue indefinitely if EF < 40% or clinical
HF
– Rx for all asymptomatic patients with LVEF 
35%
– Rx for all symptomatic patients with LVEF 
35%
– Target dose use in clinical trials or max
tolerated dose
ACE Inhibitors in CHF
Study
No.
Males
Age
EF%
Class
Drug
F/U
V-HeFT
642
100%
58
30
II.III
CONCENSUS
253
70%
70
NA
IV
HDZN/
ISDN
Enalapril
V-HeFT II
804
100%
61
29
II,III
Enalapril
SOLVD
Treatment
SOLVD
Prevention
2569
80%
61
25
II,III
Enalapril
4228
89%
59
28
I,II
Enalapril
2.3
yrs.
188
Days
2.5
yrs.
41.4
mo.
37.4
mo.
Mortality
Reduction
%
11
27
14
16
8
ACE Inhibitors Post MI
Trial
No.
SAVE
CONCENSUS II
AIRE
GISSI 3
ISIS 4
TRACE
Chinese study
SMILE
2231
6090
2006
20,000
60,000
1749
10,000
1556
Entry
Criteria
EF<40%
ALL
CHF
All
All
LVD
All
AWMI
Drug
Captopril
Enalapril
Ramipril
Lisinopril
Captopril
Trandolapril
Captopril
Zofenopril
Initiation
Period
3-16 days
<24 hours
3-10 days
< 24 hours
24 hours
3-7 days
< 36 hours
< 24 hours
F/U Period
2-5 years
1.5-6 months
6-30 months
6 weeks
5 weeks
2-4 years
5 weeks
5 weeks
Effect on
Mortality
+
+
+
+
+
+
+
Overview of Long Term ACE Inhibitor
Trials Showing Mortality Benefit
Study
SOLVD
Number Criteria RRR % ARR %
NNT
Lives
saved/1000
2569
LVEF
 35%
16
4.5
22
50
SAVE
2231
19
4.2
24
45
AIRE
2006
LVEF
 40%
Clinical
CHF
27
5.7
18
60
TRACE
1749
LVEF
35%
22
7.6
13
90
Treatment
What’s New in Ace inhibition in HF
Long Term Follow-up
X-SOLVD
Effect of Enalapril on 12-Year Survival
and Life Expectancy in Patients with
Left Ventricular Systolic Dysfunction
X-SOLVD Investigators
Philip Jong,* Salim Yusuf,* Michel F. Rousseau,**
Sylvie A. Ahn,** Shrikant I. Bangdiwala***
*Population Health Research Institute, McMaster University - Hamilton, Canada
**Division of Cardiology, University of Louvain - Brussels, Belgium
***Collaborative Studies Coordinating Center, University of North Carolina - Chapel Hill, USA
SOLVD
D
LV
Mortality
SO
X
SOLVD Prevention
SOLVD Treatment
0.5
2P=0.0072 at 4 years
30
HF Development
0.3
0.3
0.2
0.2
0.1
0.1
Relative Risk 0.63
(95% CI 0.56-0.72)
p<0.001 at 4 years
35
0.4
Mortality
0.4
Development in Prevention Trial
40
0.5
2P=0.30 at 4 years
Mortality
D
LV
HF
SO
X
in SOLVD Trials
25
20
15
10
Enalapril (n=399)
Placebo (n=436)
0.0
Enalapril (n=299)
Placebo (n=333)
0.0
0
1
2
3
4
Years after Randomization
0
1
2
3
4
Years after Randomization
Adapted from: The SOLVD Investigators. N Engl J Med 1992;327:685-691 &
N Engl J Med 1991;325:293-302.
Enalapril (n=438)
Placebo (n=640)
5
0
0
6
12
18
24
30
36
Months after Randomization
Adapted from: The SOLVD Investigators. N Engl J Med 1992;327:685-691.
42
48
X-SOLVD
D
LV Cumulative 12-Year
SO
X
in Prevention Trial
Trial Termination
0.86
0.9
Enalapril
Placebo
5-year
0.77
0.8
0.84
0.7
0.73
0.6
In-Trial
Period
0.5
0.47 (n=319)
0.4
0.41 (n=297)
0.3
0.2
Enalapril
Placebo
0.9
0.8
0.7
0.64
5-year
0.53
0.6
In-Trial
Period
0.5
p=0.01
at 12 years
0.60
0.4
0.49
0.21 (n=153)
0.3
0.2
p=0.001
at 12 years
0.1
Survival
Trial Termination
1.0
Proportion of Survivors
1.0
Proportion of Survivors
D
LV Cumulative 12-Year
SO
X
in Treatment Trial
Survival
0.20 (n=151)
0.1
0.0
0.0
0
1
2
3
4
5
6
7
8
9
10
11
12
Years after Randomization
Number at Risk
Enalapril 2111
Placebo
2117
1917
1901
1736
1664
1533
1457
Adapted from Jong et al. Lancet 2003;361:1843-1848.
1348
1252
0
1
2
3
4
5
6
7
8
9 10
Years after Randomization
11
12
Number at Risk
1010
935
319
297
Enalapril
Placebo
1285
1284
1009
940
785
719
Adapted from Jong et al. Lancet 2003;361:1843-1848.
612
562
454
425
346
328
153
151
Optimal Dosing of
ACE Inhibitors
• General Guideline:
• Start low and titrate to
the target dose used in
the clinical trials or the
MAXIMUM
TOLERATED DOSE
(ATLAS trial)
• Captopril 6.25-12.5 mg
50 mg BID-TID
(SAVE)
• Enalapril 2.5 mg BID
20 mg BID (SOLVD/X)
• Ramipril 2.5 mg BID 
5 mg BID (AIRE/EX)
• Lisinopril 10 mg OD 
30-40 mg OD (GISSI 3)
• Trandolapril 1mg  4 mg
(TRACE)
Summary – ARBs in CHF
# pts.
ELITE II
Val-HeFT
VALIANT
CHARM
ARB vs ACEI
ARB vs
placebo
( ACEI BB)
Captopril,
Valsartan or
Combination
ARB vs placebo ( ACEI)
3,152
5,010
4909/4909/4885
7,601
Symptomatic HF Class II-III/ 
clinical or radiologic LV function/preserved LVF
(added+alternative/preserved)
HF
Population
Heart failure
Heart failure
Post MI with
Endpoints
1o All-cause
mortality,
sudden death
or resuscitated
cardiac arrest:
NS
1o All-cause
mortality: NS
1o All-cause
mortality: NS
2o CV Death, MI, or
HF:NS
1o All-cause mortality: NS
Valsartan noninferior to Captopril
–ACEI+ARB = -15%
1o Combined
M/M:
ACEI+ARB = 13.2%
ACE intolerant:
-33% all cause
mortality
2o CV death or HF
hospitalization:
•CHARM Added:
•CHARM Alternative:
–ARB = -30%
•CHARM Preserved: NS
Combined Morbidity/Mortality in
Subgroups: Val-HeFT
All
Demographics
< 65
65
Male
Female
Favors valsartan
No. patients
5010
Favors placebo
2660
2350
4007
1003
Etiology/Co-morbidity
IHD (yes)
2865
IHD (no)
2145
Diabetes (yes)
1276
Diabetes (no)
3734
Disease Severity
NYHA II
NYHA III/IV
EF  27
EF < 27
LVIDD < 3.57
LVIDD  3.57
3095
1910
2623
2385
2505
2505
0.4
Cohn JN, et al: Val-HeFT NEJM December 2001
0.6
0.8
1.0
1.2
1.4
Mortality in SAVE,
TRACE, AIRE, and VALIANT
Hazard Ratio for Mortality
SAVE
TRACE
Valsartan preserves
99.6% of mortality
benefit of captopril,
representing a 25% RR
AIRE
Combined
VALIANT
(imputed placebo)
0.5
Favors
Active Drug
Pfeffer M et al. N Engl J Med 2003;349:1893-906
1
Favors
Placebo
2
CHARM Programme
Mortality and morbidity
All Cause Mortality
0.77
Alternative
p=0.0004
0.85
Added
p=0.011
0.89
Preserved
Overall
CV Death or
CHF Hospitalisation
p=0.118
0.91
p=0.055
0.7 0.8 0.9 1.0 1.1 1.2
Hazard ratio
p heterogeneity=0.37
0.84
p<0.0001
0.6 0.7 0.8 0.9 1.0 1.1 1.2
Hazard ratio
p heterogeneity=0.43
Evidence for Various ARBs
Diovan
(valsartan)
Avapro
(irbesartan)
Cozaar
(losartan)
Atacand
(candesartan
cilexetil)
Micardis
(telmisartan)
Teveten
(eprosartan)
-45%
-6%
-35%
-30%
N/a
N/a
Heart failure
hospitalizations
-27.5%
(ValHeFT)
N/a
-8.1%
(ELITE II)
-17%
(CHARM)
N/a
N/a
CV outcome in
CHF-treated
patients
-13.3%
(ValHeFT)
N/a
+7%
(ELITE II)
-15%
(CHARM)
N/a
N/a
Positive CV
outcomes in
CHF
Yes
N/a
No
Yes
N/a
N/a
Equivalent
Efficacy to ACEi
post MI
Yes
N/a
No
N/a
N/a
N/a
Reduction in
microalbuminuria with
starting dose
-Blocker Saves Lives
in Heart Failure?
–blocker is the most important progress in
Heart Failure Rx in the last 5 years
HF Trials Modulating  receptors
Trial
US
US Carvedilol
Carvedilol
Aus-NZ
CIBIS II
MERIT
COPERNICUS
COPERNICUS
HF Pts
II-III
II
EF<35%
EF<40%
EF<25%
N
Rx
RR
1,094 Carvedilol 0.35
415 Carvedilol 0.74
2,647 Bisoprolol 0.66
3,991 Metopr-CR 0.66
2,289 Carvedilol 0.65
Background Rx = ACEi + Diuretics +/- Digoxin
Number Need to Rx in HF
TRIAL
Therapy
Enalapril
vs. Plac
Metoprolol
MERIT
vs. Plac
Bisoprolol
CIBIS-2
vs. Plac
COPERN Carvedilol
ICUS
vs. Plac
Spiro vs.
RALES
Placebo
SOLVD
Lee, Liu, Packer
Annual
Annual
Absolute NNRx/year
Mortality- Mortality- Risk
to Save
Placebo Treatment Reduc’n One Life
12.5%
11.2%
1.3%
77
11.0%
7.2%
3.8%
26
13.2%
8.8%
4.4%
23
18.5%
11.4%
7.1%
14
22.5%
15.8%
6.7%
15
-adrenergic Blocking Agents
• Titrate to target dose
– Bisoprolol 1.25 -10 mg OD
– Carvedilol 3.125 - 25 mg BID
– Metoprolol 12.5 - 50 to75 mg /BID
• If unable to tolerate high dose -blocker
maintain highest tolerated dose
• Continue indefinitely
Patient Selection for Successful
 - Blocker Initiation
•
•
•
•
Stable symptoms
Stable background heart failure medications
No recent CV hospitalization
Stable CV status (no hypotension or
bradycardia)
• Euvolemic status
• Start low and titrate slowly
Patients With Heart Failure Who
Should Not Be Started on -blockers
• General Contraindications
– Bronchospastic pulmonary disease
– Severe bradycardia, high degree AV block,
sick sinus syndrome
• Heart Failure Considerations
– Congestive symptoms at rest (NYHA Class IV)
– Patients who require intravenous therapy for HF
– Unstable symptoms or recent changes in
background medications
– Hospitalized patients (especially for worsening HF)
RALES Trial
• Spironolactone 12.5-25 mg OD added to
ACE-inhibitor/diuretic/+/- digoxin in stable
Class III-IV CHF/LVEF 
35%/CR<220/K<5.0
• 30% RRR in death from progressive HF and
sudden cardiac death
• 35% reduction in hospitalization for
worsening HF
•
NEJM Volume 341:709-717 Number 10
RALES Caveats
• With aldosterone antagonist follow K/Cr in 3-7 days
–  furosemide to avoid azotemia
• Inadequate follow-up can lead to increased rates of
hospitalization for hyperkalemia and associated mortality
– NEJM Volume 351:543-551 Number 6
• Caution:
–
–
–
–
–
Diabetics
Renal disease
Elderly
NSAIDS
COX-2 inhibitors
Severity of Heart Failure
Modes of Death
NYHA II
12%
24%
64%
NYHA III
CHF
CHF
Other
26%
Sudden
Death
59%
15%
n = 103
Other
Sudden
Death
n = 103
NYHA IV
CHF
33%
11%
Other
56%
Sudden
Death
n = 27
MERIT-HF Study Group. LANCET
1999;353:2001-07.
Therapies Provided by Today’s
Dual-Chamber ICDs
Atrium
 AT/AF tachyarrhythmia detection
 Antitachycardia pacing
 Cardioversion
Ventricle
Atrium &
Ventricle
 VT/ VF detection
 Bradycardia sensing
 Antitachycardia pacing
 Bradycardia pacing
 Cardioversion
 Defibrillation
Evaluate for Implantable Devices
Consider EPS Referral
VT:
• Symptomatic sustained or non-sustained ventricular
arrhythmia (LVEF 30-40%)
AICD:
• Prior MI/CAD (LVEF  30% with IVCD  0.12 sec:
MADIT II) or both CRT/AICD(NYHA III-IV;QRS 
0.12:COMPANION).
• CHF: (NYHA II-III & LVEF < 35% SCD-HeFT)
Cardiac Resynchronization Therapy (CRT):
• (NYHA Class III-IV with reduced ejection fractions; LVEF
< 35%
• QRS duration  0.13 with IVCD or LBBB: MIRACLE /
MUSTIC)
Sudden Cardiac Death-Heart Failure
SCD-HeFT
Hypothesis and Primary Endpoint
• To determine, by intention-to-treat analysis, if
amiodarone or a conservatively programmed
shock-only single lead ICD reduces all-cause
mortality compared to placebo* in patients with
either ischemic or non-ischemic NYHA Class II
and III CHF and EF < 35%.
• Good background Therapy
– ACE or ARB 87%
– -blocker 78%
Bardy G et al.
NEJM 2005; 352:3
Sudden Cardiac Death
SCD-HeFT
Heart Failure
Trial
*Double-blind for drug therapy
Enrollment Scheme
DCM + CAD and CHF
EF < 35%
NYHA Class II or III
6 minute walk, Holter
R
Bardy G et al.
NEJM 2005; 352:3
Sudden Cardiac Death
SCD-HeFT
Heart Failure
Trial
Placebo Amiodarone
ICD
Kaplan-Meier Estimates of Death
from Any Cause
Sudden Cardiac Death
SCD-HeFT
Heart Failure
Trial
Bardy G et al.
NEJM 2005; 352:3
Kaplan-Meier Estimates of Death
from Any Cause:
Ischemic CHF
Sudden Cardiac Death
SCD-HeFT
Heart Failure
Trial
Non-Ischemic CHF
Bardy G et al.
NEJM 2005; 352:3
Hazard Ratios for the Comparison of
Amiodarone and ICD Therapy with Placebo
Sudden Cardiac Death
SCD-HeFT
Heart Failure
Trial
Bardy G et al. NEJM 2005; 352:3
SCD-HeFT: Primary Conclusions
1. In class II or III CHF patients with EF < 35% on
good background drug therapy, the mortality rate
for placebo-controlled patients is 7.2% per year over
5 years
2. Simple, single lead, shock-only ICDs decrease
mortality by 23%
3. Amiodarone, when used as a primary preventative
agent, does not improve survival
Sudden Cardiac Death
SCD-HeFT
Heart Failure
Trial
Bardy G et al.
NEJM 2005; 352:3
Cardiac Resynchronization
Therapy (CRT)
• Atrial-biventricular
stimulation
• Electrical
synchronization 
narrower QRS
• Mechanical
synchronization 
reverse remodeling
Resynchronization/Defibrillation for
Advanced Heart Failure Trial
RAFT
Hypothesis:
In patients with LV Dysfunction (EF  30%)
and QRS duration  120 ms with moderate to
severe CHF symptoms, the addition of Cardiac
Resynchronization Therapy (CRT) to
Implantable Cardioverter Defibrillator (ICD)
and optimal medical therapy reduces the
combined end point of mortality and CHF
hospitalization.
RAFT - Design
• Randomized Controlled Trial:
– ICD vs CRT/ICD
• Blinding
– Patient, HF Care (Blinded)
– Device care (Un-blinded)
• Patients randomized to a 1:1 proportion to:
– ICD (Single or Dual) or
– CRT/ICD
• Stratified for: Center & AF & Single/Dual ICD
indication
RAFT Inclusion Criteria
• NYHA Class II or III
• QRS duration  120 ms or Paced QRS  200 ms
• LVEF  30% by MUGA or LVEF  30% and LVEDD > 60mm by
echocardiogram within 6 months of randomization
• ICD indication: 1° or 2° prevention
• Optimal Heart Failure Pharmacotherapy
• Normal sinus rhythm or
Chronic persistent atrial tachyarrhythmia with resting ventricular Heart
Rate of ≤ 60 bpm and ventricular rate ≤ 90 bpm during a 6 minute hall
walk or
Chronic persistent atrial tachyarrhythmia with resting ventricular Heart
Rate of >60 bpm and ventricular rate > 90 bpm during a 6 minute hall
walk and booked for an AV junction ablation
*NYHA Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue or
dyspnea
** NYHA Class III: Marked limitation of physcial activity. Comfortable at rest, but less than ordinary activity causes fatigue or
dyspnea.
RAFT Exclusion Criteria
• In-hospital patients who have an acute cardiac or noncardiac
illness that requires intensive care
• Intra-venous inotropic agent 4 days prior to randomization
• Expected to undergo cardiac transplantation within one year
(status I)
• Coronary revascularization (CABG or PCI) < 1month
• Acute coronary syndrome(including MI) < 4 weeks
• Patients with an existing ICD (Patients with an existing
pacemaker may be included if the patient satisfies all other
inclusion/exclusion criteria)
• Uncorrected or uncorrectable primary valvular disease
• Restrictive, hypertrophic or reversible form of cardiomyopathy
RAFT Exclusion criteria cont’d
• Patients with a life expectancy of less than one year from noncardiac cause.
• Patients included in other clinical trial that will affect the
objectives of this study
• Unable or unwilling to provide informed consent
• History of noncompliance of medical therapy
• Severe primary pulmonary disease such as cor pulmonale
• Tricuspid prosthetic valve
Heart Failure Management Issues
•
•
•
•
•
•
•
High Mortality
High re-admission rates
Poor understanding of disease
Poor Rx adherence
On-going symptoms
Reduced Quality of Life
Dose Adjustments in the Elderly
Adherence Gap
•
•
•
•
•
•
•
Cost of medications
Complacency-patient and physician
Side effects
Lack of understanding
Infrequent monitoring intervals
Lack of reinforcement
Lack of feedback
Adherence Strategies
•
•
•
•
•
•
Patient education materials
Medication monitoring strategies
Pharmacy patient surveillance
Follow-up protocols
Role of Public Health nurses
Patient Awareness Initiatives
– Out-patient Heart Failure Education Programs
CHF Implementation Targets
• Heart Failure Specialists
• General Cardiologists
– Academic/Community
• Internists
– Academic/Community
•
•
•
•
•
Family Physicians
Hospital Nursing staff
Public Health Nurse
Residents & Housestaff
General Public
How can we amplify the impact
of HF therapy?
Inotropes,Devices
Transplant
4º
Specialist/Cardiologist
HF Clinic
2º & 3º
Dosing Optimization- Family
MD & Specialist
1º & 2º
Recognition-Initial TherapyFamily MD
Primary Care Physician
Community Based
Awareness/Understanding
HF Awareness Program/PHN
Heart Failure Network
•
•
•
•
•
•
•
Apically connected tertiary centres
Vertically integrated local networks
Laterally integrated at all levels
Regional centres linked to local specialist
Hubs of resources dissemination
Shared resources/minimize duplication
Common denominator is primary care
physician/patient base
Heart Failure Networks
Lateral Integration
Role of Heart Failure Clinics
• 4º and 3º Heart Failure Clinics
–
–
–
–
–
–
Pre-transplant work-up
Out-patient parenteral inotropic therapy
Patient education
High risk rehabilitation programs
Regional hubs- national Heart Failure Network
Co-ordinating centre-Heart Failure Network
data-base
Role of Heart Failure Clinics
• 2º hospital based and community based Heart
Failure Clinics/Disease Management Programs
–
–
–
–
–
–
Patient identification and risk assessment
Patient education
Rx titration and fluid status monitoring
Low risk and intermediate risk exercise programs
Primary care liaison, education
Long term follow-up
Role of Primary Care Physician
•
•
•
•
Patient identification
Assess etiology
Assess LV Function
Initial stabilization of
acute HF
– Rx initiation and
titration
(diuretics/ACEinhibitor/digoxin)
• Optimize ACE
inhibitors
• Rx -blocker if
comfortable with Rx
• Patient education
• Treatment integration
• Long term follow-up
Role of Public Health Nurse
•
•
•
•
Patient education
Patient monitoring
Adherence
Follow-up
Role of the Public
•
•
•
•
•
Awareness
Initiate contact
Understanding
Lifestyle & diet modification
Compliance
Goals & Outcomes
• Improve symptoms
• Improve quality of life
• Prevent progression of
LV dysfunction
• Reduce hospitalization
and morbidity
• Reduce mortality
– Progression of HF
– Sudden death