Management of Chronic Heart Failure

1
Management of Chronic Heart Failure

• DR.SAMEER AMBAR
• DEPT OF CARDIOLOGY
• JNMC BELGAUM, INDIA
• drsameerambar_at_rediffmail.com

2
(No Transcript)
3
(No Transcript)
4

• Asses the functional class
• BP lt130/80 mm of Hg
• Good glycaemic control
• LIPIDS LDL lt 100 (IHD) lt70 (DM)
• Avoid smoking, alcohol
• Sodium restriction lt2gms /day
• Fluid restriction ,2 Litres/day

5
(No Transcript)
6
(No Transcript)
7
ACEI MECHANISM OF ACTION
VASOCONSTRICTION
VASODILATATION
ALDOSTERONE
PROSTAGLANDINS
VASOPRESSIN
tPA
Kininogen
SYMPATHETIC
Kallikrein
Angiotensinogen
RENIN
BRADYKININ
Angiotensin I
Kininase II
A.C.E.
Inhibitor
ANGIOTENSIN II
Inactive Fragments
8
(No Transcript)
9
(No Transcript)
10
ACEI IN POST MI HF

• SAVE (NEJM 1992 327669-677)
• 2231 pts EFlt40, 3-16d post MI, without sx of
  heart failure,
• Up to 50 mg Captopril tid for 42 mo
• AIRE (Lancet 1993342821)
• 2006 patients 3-10 days post MI with any evidence
  of post infarct clinical HF,
• Up to 5 mg Ramipril bid for 15 mos
• TRACE (NEJM 1995 333 1670-1676)
• 1749 pts 3-7 days post MI with EFlt35, with or
  without symptomatic HF
• trandolapril for 24-50 mos

11

• Mortality
• SAVE 25 (placebo) vs 20 (captopril) - 19 RRR
• AIRE 23 (placebo) vs 17 (ramipril) - 27 RRR
• TRACE 42.3 (placebo) vs 34.7 (trandolapril)-
  24 RRR

12
(No Transcript)
13
(No Transcript)
14
ARBs Clinical Study

• 1.Elite-II. Study
• Enrolled Target CHF Pt
• Drug losartan v.s. captopril
• Primary EndpointCHF Improvement
• Result losartan is not better than captopril
• 2.Va-HeFT Study
• Enrolled Target CHF Pt
• Drug valsartan Usual Group v.s. Usual
  Group
• Primary Endpoint CHF Event-Free Probability
• Result Reduce M/M by 13.3

15
CHARM-Alternative
Primary outcome of CV death or CHF hospitalization
50
406 (40.0)
Placebo
40
334 (33.0)
30
Proportion With CV Death or CHF Hospitalization
()
Candesartan
20
10
HR 0.77 (95 CI 0.67-0.89), P.0004Adjusted HR
0.70, Plt.0001
0
0
1
2
3
3.5
Years
Number at risk Candesartan 1,013 929 831 434 122
Placebo 1,015 887 798 427 126
Granger CB, et al. Lancet. 2003362772-776.
16
55 on BB
17
(No Transcript)
18
When to use Angiotensin receptor blockers

• 1. There has been no definite mortality or
  morbility advantage of ARBs over ACE inhibitors
  demonstrated
• 2. Consider ARB in patient who is ACE inhibitor
  eligible if the patient is intolerant of ACE
  inhibitors because of cough, renal insufficiency,
  or hyperkalemia

19
When to use Angiotensin receptor blockers

• 3. In the patient who is apparently ACE inhibitor
  intolerant, rule out other causes of presumed
  side effect
• a. Cough-evaluate for pulmonary edema
• b. Hyperkalemia-concurrent potassium
  supplementation, potassium-sparing diuretic use
• c. renal insufficiency-evaluate for prerenal
  azotemia, NSAID use
• 4. The incidence of cough and hyperkalemia is
  lower with ARBs versus ACE inhibitors
• There does not appear to be a significant
  difference in incidence of renal insufficiency

20
(No Transcript)
21
Beta blockade in Heart failure

• Beta receptor levels in heart failure
• Normal Heart B1 80 B2 20
• Severe Heart Failure B1 60 B2 40
• B1 receptors to selectively down-regulate
  secondary to high levels of catecholamine
• B2 agonists retain full inotropic activity
  mediated through a B2 population that is not
  significantly decreased

22
(No Transcript)
23
Effect of Sympathetic Activation in Heart Failure

• CNS Sympathetic Outflow

• Sympathetic activity to
• kidneys blood vessels

• Cardiac sympathetic Activity

• 1
• Receptors

• 1
• Receptors

• 2
• Receptors

Activation of RAS
Myocyte death Increased arrhythmias
Vasoconstriction Sodium retention
Disease Progression
24
(No Transcript)
25
Benefit Of Beta Blockers

• Improve symptoms and clinical status
• Increase LV ejection fraction
• Little effect on exercise tolerance
• Reduce frequency of hospitalizations for heart
  failure
• Decrease mortality

26
Action

• Time dependant improvement in LV remodelling
• Reduce cetecholamine myocyte toxicity
• Improved B1 signaling
• Antiapoptosis
• antiarrthymic
• RAAS inhibition

27
Sympathetic Activation
B2 Receptors
A1 Receptors
B1 Receptors
Metoprolol
Propranolol
Carvedilol
Cardiotoxicity
28
(No Transcript)
29
(No Transcript)
30
(No Transcript)
31
(No Transcript)
32
Clinical Trials

• Prospective Randomized Evaluation of Carvedilol
  on Symptoms and Exercise (PRECISE)
• 278 patients with chronic stable symptomatic
  heart failure EFlt35 despite diuretics and ACE
• Carvedilol group was associated with greater
  improvement in NYHA Class
• 39 reduction in combined risk of
  death/hospitalization for any reason
• 46 reduction in risk of hospitalization for
  cardiovascular reason

Circulation 1996942793-2799
33
Clinical Trials

• Merit-HF Trial( metaprolol randomised
  interventional trial in CHF)
• 3991 patients with an ischemic or nonischemic
  cardiomyopathy (NYHA Class II or III) randomized
  to either Metoprolol XL up to 200mg/day or
  placebo.
• Metoprolol XL was associated with a 35 reduction
  in mortality

Amer J Cardiol 19978054J-58J
34
MERIT-HFMETOPROL-XL Mortality and Morbidity
MERIT-HF Study Group. Lancet. 19993532001-2007
35
MERIT-HF
Post-MI Patients with Severe Heart Failure (n
384)

• NYHA III/IV
• EF lt0.25

Jánosi A et al, Am Heart J 2003146721-8
36
MERIT-HF
Post-MI Patients
Total Mortality
20
Placebo
15
p 0.0004
Metoprolol CR/XL
10
Per cent
Risk reduction 40
5
0
0
3
6
9
12
15
18
Months of follow-up
Jánosi A et al, Am Heart J 2003146721-8
37
MERIT-HF
Post-MI Patients
Sudden Death
12
Placebo
9
p 0.0004
Metoprolol CR/XL
6
Per cent
Risk reduction 50
3
0
0
3
6
9
12
15
18
Months of follow-up
Jánosi A et al, Am Heart J 2003146721-8
38
MERIT-HF
Post-MI Patients
Death from Worsening Heart Failure
5
Placebo
4
p 0.021
3
Metoprolol CR/XL
Per cent
2
Risk reduction 49
1
0
0
3
6
9
12
15
18
Months of follow-up
Jánosi A et al, Am Heart J 2003146721-8
39
MERIT-HF
Post-MI Patients
Total Number of Hospitalizations
Heart failure
All-cause
CV cause
-32
-8
-17
p0.006
ns
p0.037
Jánosi A et al, Am Heart J 2003146721-8
40
MERIT-HF
Post-MI Patients
Risk reduction
Events Plac/Beta
Total mortality
122/74 44/24 37/26
40
All Post-MI patients
Post-MI severe CHF
History of revasc. (PTCA or CABG)
Cardiac death/nonfatal MI
132/74 46/22 42/27
45
All Post-MI patients
Post-MI severe CHF
History of revasc. (PTCA or CABG)
0.0
1.0
Relative risk and 95 CI
Jánosi A et al, Am Heart J 2003146721-8
41
MERIT-HF
Effect of metoprolol and placebo treatment on
survival and hospitalization risk in class III
and IV HF

Endpoint Metoprolol (N) Placebo (N) Risk reduction () p value
Total mortality 45 72 39 0.0086
CV mortality 40 70 44 0.0028
Sudden death 22 39 45 0.024
Death from worsening HF 13 28 55 0.015
Total hospitalizations 273 363 27 0.0037
Total hospitalizations due to worsening HF 105 187 45 lt0.0001
Goldstein S et al. J Am Coll Cardiol 2001
38(4)932-8
42
MERIT-HF
Comparison of findings in subanalysis and entire
MERIT-HF cohort
Endpoint Reductions in entire MERIT-HF cohort Reductions in class III and IV MERIT-HF subset
Total mortality -34 -39
Sudden death -41 -45
Death due to worsening HF -49 -55
Goldstein S et al. J Am Coll Cardiol 2001
38(4)932-8
43
MERIT-HF
Post-MI Patients
Summary
Mortality/Hospitalizations

• 40 reduction in Total Mortality
• 50 reduction in Sudden Death
• 32 reduction in number of hospitalizations for
  Worsening Heart Failure

Jánosi A et al, Am Heart J 2003146721-8
44
(No Transcript)
45
Carvedilol Prospective Randomized Cumulative
Survival Trial (COPERNICUS)

• Enrolled 2289 patients with severe HF (LVEF
  lt25)
• Randomized to carvedilol in a target dose of 25
  mg bid for up to
• 29 months

35 reduction in the risk of all-cause mortality
among patients with severe congestive heart
failure (CHF) treated with carvedilol compared to
placebo
46
COPERNICUS and CAPRICORN
COPERNICUS Effect of carvedilol on the combined
risk of morbidity and mortality
Odds ratio
p value
Endpoint
Relative risk reduction
0.76
0.00004
Death or hospitalization for any reason
24
Death or hospitalization for a CV reason
27
0.73
0.00002
0.69
Death or hospitalization for HF
0.000004
31
47
Beta BlockersPost MI LV dysfunction

• CAPRICORN( carvedilol post infarct survival
  control in LVD)
• 1959 pts post MI LVEFlt40
• Randomized to carvedilol or placebo
• Results
• Lower all cause mortality (12 vs. 15)
• Lower non-fatal MI

Lancet 2001 357 138590
48
CAPRICORN All-Cause Mortality
Carvedilol Post-Infarct Survival Control in LV
Dysfunction
1.00
Carvedilol n975
0.90
0.80
Proportion Event-free
Placebo n984
Risk reduction
0.70

• 23
• (2, 40)

0.60
Mortality Rates Placebo 15 Carvedilol 12
0
0
0.5
1
1.5
2
2.5
Years
The CAPRICORN Investigators. Lancet.
20013571385-1390.
49
Clinical Use Of Beta Blockers

• Recommended for patients with NYHA class II-IV
• General contraindications
• Decompensated heart failure
• Severe claudication
• Bronchospasm
• Advanced heart block
• Use with caution if patient requires inotropes
  for support of circulatory function

50
Beta-Blockade

• Cardiac Output

• Renal
• Blood Flow

Worsening Heart Failure
Sodium Retention
51
Considerations in selecting a beta-blocker

1. Patients should be clinically stable and
   euvolemic before initiating beta-blocker therapy
2. Start at low doses and titrate upward gradually
   (doubling every 2-4 weeks)
3. Patients may experience an initial exacerbation
   of heart failure symptoms because of transient
   worsening of cardiac output

52
Clinical Use Cont . . .

• Clinical response may not be seen until 2 to 3
  months after initiation of therapy
• Abrupt withdrawal can lead to dramatic
  deterioration
• Patient education paramount

53
Outcome in Post-MI Patients with Heart Failure
CAPRICORN and MERIT-HF
p- value
Risk reduction
Plac/Beta
All-cause mortality
151/116 122/74
CAPRICORN
23
p0.03
Carvedilol ?1 ?2 (?1)
MERIT-HF
40
p0.0004
Metoprolol CR/XL ?1
All-cause mortality/CV hosp.1
367/340 326/258
8
CAPRICORN
ns
Carvedilol ?1 ?2 (?1)
MERIT-HF
p0.002
22
Metoprolol CR/XL ?1
0.0
1.0
Relative risk and 95 CI
1Time to first event
The CAPRICORN Investigators, Lancet
20013571385-90 Jánosi A et al, Am Heart J
2003146721-8
54
LVEF Change From BaselineWithin Treatment-arm
Comparison
P lt 0.05 P lt 0.01 P lt 0.001
55
Diuretics
56
(No Transcript)
57
Diuretics
58
(No Transcript)
59
RALES(randomised aldactone evaluation study)

• issues
• only 10 of patients on beta blockers

• 1663 patients Class 3-4 CHF, LVEFlt35 on
  ACE-inhibitor/diuretic/dig
• randomized to 25 mg spironolactone vs. placebo

NEJM 1999341709-17
60
RALES

• Results 46 mortality placebo vs 35
  spironolactone (30 RRR)
• adverse effects
• 10 of pts in spironolactone group developed
  gynecomastia.
• -serious hyperkalemia (Kgt6) 14 vs 10 (not
  statist sig)

61
EPHESUS(eplerenone post AMI HF efficacy and
survival study)

• 6642 patients
• a) 3-14 days post MI,
• b) EFlt40,
• c) CHF (rales, pulm venous congestion seen on
  CXR, 3rd heart sound) OR Diabetes
• randomized to 25 mg eplerenone titrated up to 50
  mg po qd

NEJM 20033481309-21
62
EPHESUS

• Results
• One year mortality 15 risk reduction (11.8 vs
  13.6)
• CV death or cardiovascular hospitalizations (26
  vs 30.0)
• (75 of patients on beta blockers)
• adverse effects
• serious hyperkalemia (Kgt6) Epler- 5.5 vs plac-
  3.9 (p.002)
• serious hypokalemia (Klt3.5) Epler- 8.4 plac-
  13.1 (plt.001)
• gynecomastia- 0.5 vs 0.6

63
Criteria for treatment with spironolactone

• New York heart Association class 3-4
• Left ventricular ejection fraction lt35
• Serum creatinine lt2.5 mg/dL
• Serum potassium lt5 mmol/L
• Baseline treatment with ACE inhibitor (or other
  vasodilator if ACE inhibitor intolerance), loop
  diuretic, and digoxin as indicated

64
Digoxin

• Digoxin has a significant role in improving
  symptoms and rehospitalization rate
• No impact on the total and cardiovascular
  mortality
• Usually used only in severe CHF or in patients
  who remain symptomatic with optimal treatment
• Digoxin is useful in CHF with atrial fibrillation

65
Digoxin

• DIG trial
• 6800 pts EF lt45
• 0.25 mg/day
• 22 reduction in hospitalisation
• No mortlity benefit
• 28 RRR of death in post hoc analysis

66
(No Transcript)
67
Nesiritide

• Identical to human BNP
• Causing vasodilation and decrease LV filling
  pressure
• Decrease pulmonary capillary wedge pressure
• Improves patients symptoms
• Improvement in hemodynamics VMAC trial 5.8 mm of
  hg decrease on PCW

68
Nesiritide

• 2 mcg/kg bolus infusion 0.01-0.03 mcg/kg/min for
  3 hrs
• Improved safety profile compared with dobutamine
  with fewer arrhythmias and better outcomes
• It should not be used in patients who are
  overdiuresed, hypotensive, or present with other
  signs of inadequate perfusion -Worsening of renal
  failure (45)

69
(No Transcript)
70
Inotropes

• Inotropes direct adrenergic agonists,
  phosphodiesterase inhibitors, and dopaminergic
  agonists
• Inotropes improve short term hemodynamics, they
  do not improve and in several cases may worsen
  long-term survival
• Oral inotropic agents have resulted in excess
  mortality in patients with HF

71
Amiodarone

• Antiarrhythmic effect
• Low dose amiodarone was safe and significantly
  reduced 2-year mortality (33.5 vs 41.4, p0.02)
• in patients with moderate to severe HF (GESICA
  trial)
• Another trial did not demonstrate mortality
  benefit, either all-cause or sudden death

72
Anticoagulation

• LVEF lt 30
• LV thrombus
• Atrial fibrillation
• INR 2-3

73
(No Transcript)
74
Thank you