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Management of Management of Chronic Heart Chronic Heart
FailureFailureDR.SAMEER AMBARDR.SAMEER AMBAR
DEPT OF CARDIOLOGYDEPT OF CARDIOLOGY
JNMC BELGAUM, INDIAJNMC BELGAUM, INDIA
[email protected]@rediffmail.comom
Asses the functional classAsses the functional class BP <130/80 mm of HgBP <130/80 mm of Hg Good glycaemic controlGood glycaemic control LIPIDS LDL < 100 (IHD) <70 (DM)LIPIDS LDL < 100 (IHD) <70 (DM) Avoid smoking, alcoholAvoid smoking, alcohol Sodium restriction <2gms /daySodium restriction <2gms /day Fluid restriction ,2 Litres/dayFluid restriction ,2 Litres/day
ACEIACEIMECHANISM OF ACTIONMECHANISM OF ACTION
VASOCONSTRICTIONVASOCONSTRICTION VASODILATATION VASODILATATION
KininogenKininogen
KallikreinKallikrein
Inactive FragmentsInactive Fragments
AngiotensinogenAngiotensinogen
Angiotensin IAngiotensin I
RENINRENIN
Kininase IIKininase IIInhibitorInhibitor
ALDOSTERONEALDOSTERONE
SYMPATHETICSYMPATHETIC
VASOPRESSINVASOPRESSIN
PROSTAGLANDINSPROSTAGLANDINS
tPAtPA
ANGIOTENSIN IIANGIOTENSIN II
BRADYKININBRADYKININ
A.C.E.A.C.E.
SAVE (SAVE (NEJM 1992 327:669-677)NEJM 1992 327:669-677) 2231 pts EF<40%, 3-16d 2231 pts EF<40%, 3-16d post MIpost MI, , without sx of without sx of
heart failureheart failure, , Up to Up to 50 mg Captopril50 mg Captopril tid for 42 mo tid for 42 mo
AIRE AIRE (Lancet 1993:342:821)(Lancet 1993:342:821) 2006 patients 3-10 days 2006 patients 3-10 days post MIpost MI with with any any
evidence of post infarct clinical HF, evidence of post infarct clinical HF, Up to Up to 5 mg Ramipril bid5 mg Ramipril bid for 15 mos for 15 mos
TRACE TRACE (NEJM 1995; 333: 1670-1676)(NEJM 1995; 333: 1670-1676) 1749 pts 3-7 days 1749 pts 3-7 days post MIpost MI with EF<=35%, with EF<=35%, with with
or withoutor without symptomatic HF symptomatic HF trandolapril trandolapril for 24-50 mosfor 24-50 mos
ACEI IN POST MI HF
MortalityMortality SAVE: 25% (placebo) vs 20% (captopril) - 19% RRRSAVE: 25% (placebo) vs 20% (captopril) - 19% RRR AIRE: 23% (placebo) vs 17% (ramipril) - 27% RRRAIRE: 23% (placebo) vs 17% (ramipril) - 27% RRR TRACE: 42.3% (placebo) vs 34.7% (trandolapril)- 24% RRRTRACE: 42.3% (placebo) vs 34.7% (trandolapril)- 24% RRR
HFSA 2006 Practice Guideline (7.10)
Pharmacologic Therapy: Angiotensin Receptor Blockers
ARBs are recommended for routine administration to symptomatic and asymptomatic patients with an LVEF 40% who are intolerant to ACE inhibitors for reasons other than hyperkalemia or renal insufficiency.
Strength of Evidence = A
Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.
ARBs Clinical Study:ARBs Clinical Study:
1.Elite-II. Study:1.Elite-II. Study: Enrolled Target: CHF P’t Enrolled Target: CHF P’t Drug: losartan v.s. captoprilDrug: losartan v.s. captopril Primary Endpoint:CHF Improvement Primary Endpoint:CHF Improvement Result: losartan is not better than captoprilResult: losartan is not better than captopril 2.Va-HeFT Study: 2.Va-HeFT Study: Enrolled Target: CHF P’tEnrolled Target: CHF P’t Drug: valsartan + Usual Group v.s. Usual Drug: valsartan + Usual Group v.s. Usual
Group Group Primary Endpoint: CHF Event-Free Primary Endpoint: CHF Event-Free
Probability Probability Result: Reduce M/M by 13.3%Result: Reduce M/M by 13.3%
Granger CB, et al. Lancet. 2003;362:772-776.
CHARM-AlternativeCHARM-Alternative
Number at risk
Candesartan 1,013 929 831 434 122
Placebo 1,015 887 798 427 126
0 1 2 3
Years
0
10
20
30
40
50
Placebo
Candesartan
HR 0.77 (95% CI 0.67-0.89), P=.0004Adjusted HR 0.70, P<.0001
3.5
406 (40.0%)
334 (33.0%)
Pro
po
rtio
n W
ith
CV
Dea
th
or
CH
F H
osp
ital
izat
ion
(%
)Primary outcome of CV death or CHF hospitalization
www. Clinical trial results.org
CHARM Added Trial CHARM Added Trial CHARM Added Trial
CV Mortality orCHF hospitalization
HR 0.85p=0.011
37.9%
42.3%
0%
10%
20%
30%
40%
50%
Candesartan Placebo
37.9%
42.3%
0%
10%
20%
30%
40%
50%
Candesartan Placebo
23.7%
27.3%
0%
10%
20%
30%
Candesartan Placebo
23.7%
27.3%
0%
10%
20%
30%
Candesartan Placebo
European Society of Cardiology 2003European Society of Cardiology 2003
CV MortalityHR 0.84p=0.02
55% on BB
When to use Angiotensin receptor When to use Angiotensin receptor blockersblockers
1.1. There has been no definite There has been no definite mortality or morbility advantage of mortality or morbility advantage of ARBs over ACE inhibitors ARBs over ACE inhibitors demonstrateddemonstrated
2. Consider ARB in patient who is ACE 2. Consider ARB in patient who is ACE inhibitor eligible if the patient is inhibitor eligible if the patient is intolerant of ACE inhibitors because intolerant of ACE inhibitors because of cough, renal insufficiency, or of cough, renal insufficiency, or hyperkalemiahyperkalemia
When to use Angiotensin receptor When to use Angiotensin receptor blockersblockers
3. In the patient who is apparently ACE 3. In the patient who is apparently ACE inhibitor intolerant, rule out other causes of inhibitor intolerant, rule out other causes of presumed side effect:presumed side effect:
a. Cough-evaluate for pulmonary edemaa. Cough-evaluate for pulmonary edema b. Hyperkalemia-concurrent potassium b. Hyperkalemia-concurrent potassium
supplementation, potassium-sparing supplementation, potassium-sparing diuretic usediuretic use
c. renal insufficiency-evaluate for prerenal c. renal insufficiency-evaluate for prerenal azotemia, NSAID useazotemia, NSAID use
4. The incidence of cough and hyperkalemia 4. The incidence of cough and hyperkalemia is lower with ARBs versus ACE inhibitorsis lower with ARBs versus ACE inhibitors
There does not appear to be a significant There does not appear to be a significant difference in incidence of renal insufficiency difference in incidence of renal insufficiency
Beta blockade in Heart failureBeta blockade in Heart failure
Beta receptor levels in heart Beta receptor levels in heart failurefailure
Normal HeartNormal Heart B1 80 : B2 20B1 80 : B2 20 Severe Heart FailureSevere Heart Failure B1 60 : B2 40B1 60 : B2 40
B1 receptors to selectively down-regulate B1 receptors to selectively down-regulate secondary to high levels of catecholaminesecondary to high levels of catecholamine
B2 agonists retain full inotropic activity B2 agonists retain full inotropic activity mediated through a B2 population that is not mediated through a B2 population that is not significantly decreasedsignificantly decreased
Effect of Sympathetic Effect of Sympathetic Activation in Heart Activation in Heart
FailureFailureCNS Sympathetic Outflow
Sympathetic activity to kidneys & blood vessels
Activation of RAS
VasoconstrictionSodium retention
Disease Progression
Cardiac sympathetic Activity
1 Receptors
2 Receptors
1Receptors
Myocyte deathIncreased arrhythmias
Benefit Of Beta BlockersBenefit Of Beta Blockers
Improve symptoms and clinical Improve symptoms and clinical statusstatus
Increase LV ejection fractionIncrease LV ejection fraction Little effect on exercise toleranceLittle effect on exercise tolerance Reduce frequency of Reduce frequency of
hospitalizations for heart failurehospitalizations for heart failure Decrease mortalityDecrease mortality
ActionAction
Time dependant improvement in LV Time dependant improvement in LV remodellingremodelling
Reduce cetecholamine myocyte Reduce cetecholamine myocyte toxicitytoxicity
Improved B1 signalingImproved B1 signaling AntiapoptosisAntiapoptosis antiarrthymicantiarrthymic RAAS inhibitionRAAS inhibition
Sympathetic ActivationSympathetic Activation
B1 Receptors
B2 Receptors
A1Receptors
CardiotoxicityCarvedilol
Metoprolol
Propranolol
Clinical TrialsClinical Trials
Prospective Randomized Evaluation of Carvedilol on Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise (PRECISE)Symptoms and Exercise (PRECISE) 278 patients with chronic stable symptomatic 278 patients with chronic stable symptomatic
heart failure EF<35% despite diuretics and ACE heart failure EF<35% despite diuretics and ACE Carvedilol group was associated with greater Carvedilol group was associated with greater
improvement in NYHA Classimprovement in NYHA Class 39% reduction in combined risk of 39% reduction in combined risk of
death/hospitalization for any reasondeath/hospitalization for any reason 46% reduction in risk of46% reduction in risk of hospitalization for hospitalization for
cardiovascular reasoncardiovascular reason
Circulation 1996;94:2793-2799
Clinical TrialsClinical Trials
Merit-HF Trial( metaprolol randomised Merit-HF Trial( metaprolol randomised interventional trial in CHF)interventional trial in CHF) 3991 patients with an ischemic or 3991 patients with an ischemic or
nonischemic cardiomyopathy (NYHA nonischemic cardiomyopathy (NYHA Class II or III) randomized to either Class II or III) randomized to either Metoprolol XL up to 200mg/day or Metoprolol XL up to 200mg/day or placebo. placebo.
Metoprolol XL was associated with a Metoprolol XL was associated with a 35% reduction in mortality35% reduction in mortality
Amer J Cardiol 1997;80:54J-58J
MERIT-HFMERIT-HFMETOPROL-XL: Mortality and MorbidityMETOPROL-XL: Mortality and Morbidity
MERIT-HF Study Group. Lancet. 1999;353:2001-2007
NYHA III/IVNYHA III/IV
EF <0.25EF <0.25
Post-MI Patients with Post-MI Patients with Severe Heart Failure (n= 384)Severe Heart Failure (n= 384)
Jánosi A et al, Am Heart J 2003;146:721-8
MERIT-HFMERIT-HF
Total MortalityTotal Mortality
Months of follow-upMonths of follow-up
Pe
r ce
ntP
er
cent
2020
1515
1010
55
00
PlaceboPlacebo
Metoprolol CR/XLMetoprolol CR/XL
p = 0.0004p = 0.0004
Risk reduction = 40%Risk reduction = 40%
00 33 66 99 1212 1515 1818
Jánosi A et al, Am Heart J 2003;146:721-8
MERIT-HFMERIT-HF
Post-MI PatientsPost-MI Patients
Pe
r c e
ntP
er
cen t
1212
99
66
33
00
Risk reduction = 50%Risk reduction = 50%
Sudden Death
PlaceboPlacebo
Metoprolol CR/XLMetoprolol CR/XL
p = 0.0004p = 0.0004
00 33 66 99 1212 1515 1818
Jánosi A et al, Am Heart J 2003;146:721-8
MERIT-HFMERIT-HF
Post-MI PatientsPost-MI Patients
Months of follow-upMonths of follow-up
Pe
r ce
ntP
er
cent
55
44
33
11
00
Risk reduction = 49%Risk reduction = 49%
Death from Worsening Heart FailureDeath from Worsening Heart Failure
PlaceboPlacebo
Metoprolol CR/XLMetoprolol CR/XL
p = 0.021p = 0.021
22
00 33 66 99 1212 1515 1818
Jánosi A et al, Am Heart J 2003;146:721-8
MERIT-HFMERIT-HF
Post-MI PatientsPost-MI Patients
Months of follow-upMonths of follow-up
Total Number of HospitalizationsTotal Number of Hospitalizations
Heart failure
p=0.006
-32%
All-cause
ns-8%
CV cause
p=0.037-17%
MERIT-HFMERIT-HF
Post-MI PatientsPost-MI Patients
Jánosi A et al, Am Heart J 2003;146:721-8
Post-MI severe CHFPost-MI severe CHF
Total mortalityTotal mortality
Cardiac death/nonfatal MICardiac death/nonfatal MI
History of revasc. History of revasc. (PTCA or CABG)(PTCA or CABG)
40%
45%
Risk Risk reductionreduction
EventsEventsPlac/BetaPlac/Beta
122/74
44/2444/24
37/2637/26
132/74
46/2246/22
42/2742/27
All Post-MI patientsAll Post-MI patients
Post-MI severe CHFPost-MI severe CHF
All Post-MI patientsAll Post-MI patients
Relative risk and 95% CIRelative risk and 95% CI0.00.0 1.01.0
History of revasc. History of revasc. (PTCA or CABG)(PTCA or CABG)
Jánosi A et al, Am Heart J 2003;146:721-8
MERIT-HFMERIT-HF
Post-MI PatientsPost-MI Patients
Effect of metoprolol and placebo Effect of metoprolol and placebo treatment on survival and treatment on survival and
hospitalization risk in class III and IV hospitalization risk in class III and IV HFHF
MERIT-HF
Goldstein S et al. J Am Coll Cardiol 2001; 38(4):932-8
Endpoint Endpoint MetoprolMetoprolol (N)ol (N)
PlacebPlacebo (N)o (N)
Risk Risk reductioreductio
n (%)n (%)
p valuep value
Total mortalityTotal mortality 4545 7272 39%39% 0.00860.0086
CV mortalityCV mortality 4040 7070 44%44% 0.0028 0.0028
Sudden deathSudden death 2222 3939 45%45% 0.0240.024
Death from worsening Death from worsening HFHF
1313 2828 55%55% 0.0150.015
Total hospitalizationsTotal hospitalizations 273273 363363 27%27% 0.0037 0.0037
Total hospitalizations Total hospitalizations due to worsening HFdue to worsening HF
105105 187187 45%45% <0.000<0.00011
Comparison of findings in Comparison of findings in subanalysis and entire MERIT-subanalysis and entire MERIT-
HF cohort HF cohort
MERIT-HF
Goldstein S et al. J Am Coll Cardiol 2001; 38(4):932-8
EndpointEndpoint Reductions in Reductions in entire MERIT-entire MERIT-
HF cohortHF cohort
Reductions in Reductions in class III and IV class III and IV
MERIT-HF MERIT-HF subsetsubset
Total mortalityTotal mortality -34% -34% -39%-39%
Sudden deathSudden death -41%-41% -45%-45%
Death due to worsening Death due to worsening HFHF
-49%-49% -55%-55%
40% reduction in Total Mortality40% reduction in Total Mortality
50% reduction in Sudden Death50% reduction in Sudden Death
32% reduction in number of hospitalizations for 32% reduction in number of hospitalizations for Worsening Heart Failure Worsening Heart Failure
Jánosi A et al, Am Heart J 2003;146:721-8
MERIT-HFMERIT-HF
Post-MI PatientsPost-MI Patients
Mortality/HospitalizationsMortality/HospitalizationsSummarySummary
• Enrolled 2289 patients with severe HF (LVEF <25%)• Randomized to carvedilol in a target dose of 25 mg bid for up to 29 months
Carvedilol Prospective Randomized Cumulative Survival Trial
(COPERNICUS)
35% reduction in the risk of all-cause mortality among patients with severe congestive heart failure (CHF) treated
with carvedilol compared to placebo
COPERNICUS: Effect of COPERNICUS: Effect of carvedilol on the combined risk carvedilol on the combined risk
of morbidity and mortalityof morbidity and mortality
Death or Death or hospitalization hospitalization for HFfor HF
0.000000.0000044
p valuep valueEndpointEndpoint
COPERNICUS and CAPRICORN
0.000040.00004
3131%%
Death orDeath or hospitalization hospitalization for a CV for a CV reasonreason
0.760.76
Death or Death or hospitalizatiohospitalization for any n for any reasonreason
Relative risk reduction
24%
0.00002
Odds ratio
27% 0.73
0.69
Beta BlockersBeta BlockersPost MI LV dysfunctionPost MI LV dysfunction
CAPRICORN( carvedilol post CAPRICORN( carvedilol post infarct survival control in LVD)infarct survival control in LVD) 1959 pts post MI LVEF<40%1959 pts post MI LVEF<40% Randomized to carvedilol or placeboRandomized to carvedilol or placebo Results: Results:
Lower all cause mortality (12% vs. 15%)Lower all cause mortality (12% vs. 15%) Lower non-fatal MILower non-fatal MI
Lancet 2001; 357: 1385–90
CAPRICORN All-Cause MortalityCAPRICORN All-Cause Mortality
0 0.5 1 1.5 2 2.5
Carvedilol n=975
Placebo n=984
Years
Pro
po
rtio
n E
ven
t-fr
ee
23%(2%, 40%)
Risk reduction
0
0.90
0.70
0.60
0.80
The CAPRICORN Investigators. Lancet. 2001;357:1385-1390.
Mortality Rates: Placebo 15%; Carvedilol 12%
Carvedilol Post-Infarct Survival Control in LV Dysfunction
1.00
Clinical Use Of Beta Clinical Use Of Beta Blockers Blockers
Recommended for patients with NYHA class Recommended for patients with NYHA class II-IVII-IV
General contraindications:General contraindications: Decompensated heart failureDecompensated heart failure Severe claudicationSevere claudication BronchospasmBronchospasm Advanced heart blockAdvanced heart block Use with caution if patient requires Use with caution if patient requires
inotropes for support of circulatory inotropes for support of circulatory functionfunction
Beta-Blockade
Cardiac Output
RenalBlood Flow
SodiumRetention
Worsening Heart Failure
Considerations in selecting a Considerations in selecting a beta-blockerbeta-blocker
1.1. Patients should be clinically stable Patients should be clinically stable and euvolemic before initiating and euvolemic before initiating beta-blocker therapybeta-blocker therapy
2.2. Start at low doses and titrate Start at low doses and titrate upward gradually upward gradually (doubling every (doubling every 2-4 weeks)2-4 weeks)
3.3. Patients may experience an initial Patients may experience an initial exacerbation of heart failure exacerbation of heart failure symptoms because of transient symptoms because of transient worsening of cardiac outputworsening of cardiac output
Clinical Use Cont . . .Clinical Use Cont . . .
Clinical response may not be seen Clinical response may not be seen until 2 to 3 months after initiation of until 2 to 3 months after initiation of therapytherapy
Abrupt withdrawal can lead to Abrupt withdrawal can lead to dramatic deteriorationdramatic deterioration
Patient education paramountPatient education paramount
Outcome in Post-MI Patients with Heart FailureOutcome in Post-MI Patients with Heart Failure
CAPRICORN and MERIT-HFCAPRICORN and MERIT-HF
11Time to first eventTime to first event
CAPRICORNCAPRICORNAll-cause mortalityAll-cause mortality
All-cause mortality/CV hosp.All-cause mortality/CV hosp.11
MERIT-HF MERIT-HF
23%
8%
Risk Risk reductionreduction
p-p-valuevalue
p=0.03
Plac/BetaPlac/Beta
151/116151/116
122/74122/74 40% p=0.0004
CAPRICORNCAPRICORN
MERIT-HF MERIT-HF
367/340367/340
326/258326/258
ns
22% p=0.002
The CAPRICORN Investigators, Lancet 2001;357:1385-90Jánosi A et al, Am Heart J 2003;146:721-8
Relative risk and 95% CIRelative risk and 95% CI0.00.0 1.01.0
Metoprolol CR/XL 1
Metoprolol CR/XL 1
Carvedilol 1 2 (1)
Carvedilol 1 2 (1)
LVEF: Change From BaselineLVEF: Change From BaselineWithin Treatment-arm Within Treatment-arm
ComparisonComparison
* P < 0.05; ** P < 0.01; *** P < 0.001
EnalaprilCarvedilol &Enalapril
Carvedilol
-1-1
00
11
22
33
44
55
L
VE
F (
%)
****** ****** ******
****** ****** ****
**
M6 M12 M18 M6 M18M12 M6 M12 M18
Diuretics Diuretics
Diuretics Diuretics
HFSA 2006 Practice Guideline (7.14-7.15)
Pharmacologic Therapy:Aldosterone Antagonists
An aldosterone antagonist is recommended for patients on standard therapy, including diuretics, who have:
NYHA class IV HF (or class III, previously class IV) due to LV systolic dysfunction (LVEF 35%)
One should be considered in patients post-MI with clinical HF or diabetes and an LVEF < 40% who are on standard therapy, including an ACE inhibitor or an ARB. Strength of Evidence = A
Adapted from: Adams KF, Lindenfeld J, et al. HFSA 2006 Comprehensive Heart Failure Guideline. J Card Fail 2006;12:e1-e122.
RALES(randomised RALES(randomised aldactone evaluation study)aldactone evaluation study)
1663 patients Class 1663 patients Class 3-4 CHF, LVEF<35% 3-4 CHF, LVEF<35% on on ACE-inhibitor/diuretiACE-inhibitor/diuretic/dig c/dig
randomized to randomized to 25 25 mg spironolactonemg spironolactone vs. placebovs. placebo
issues: issues: only 10% of only 10% of
patients on beta patients on beta blockersblockers
NEJM 1999:341:709-17
RALESRALES Results: 46% mortality Results: 46% mortality
placebo vs 35% placebo vs 35% spironolactone (30% spironolactone (30% RRR)RRR)
adverse effects: adverse effects: 10% of pts in 10% of pts in
spironolactone group spironolactone group developed developed gynecomastia.gynecomastia.
-serious hyperkalemia -serious hyperkalemia (K>6) 14% vs 10% (not (K>6) 14% vs 10% (not statist sig)statist sig)
EPHESUS(eplerenone post EPHESUS(eplerenone post AMI HF efficacy and AMI HF efficacy and
survival study)survival study) 6642 patients:6642 patients: a) 3-14 days a) 3-14 days post MIpost MI, , b) EF<40, b) EF<40, c) CHF (rales, pulm venous congestion c) CHF (rales, pulm venous congestion
seen on CXR, 3rd heart sound) seen on CXR, 3rd heart sound) OROR DiabetesDiabetes
randomized to randomized to 25 mg eplerenone25 mg eplerenone titrated titrated up to 50 mg po qdup to 50 mg po qd
NEJM 2003;348:1309-21
Results:Results: One year mortality: 15% risk reduction (11.8% vs One year mortality: 15% risk reduction (11.8% vs
13.6%)13.6%) CV death or cardiovascular hospitalizations (26% vs CV death or cardiovascular hospitalizations (26% vs
30.0%)30.0%)
(75% of patients on beta blockers)(75% of patients on beta blockers)
adverse effects: adverse effects: serious hyperkalemia (K>6) Epler- 5.5% vs plac- serious hyperkalemia (K>6) Epler- 5.5% vs plac-
3.9% (p=.002)3.9% (p=.002) serious hypokalemia (K<3.5) Epler- 8.4% plac- serious hypokalemia (K<3.5) Epler- 8.4% plac-
13.1% (p<.001)13.1% (p<.001) gynecomastia- 0.5% vs 0.6%gynecomastia- 0.5% vs 0.6%
EPHESUSEPHESUS
Criteria for treatment with Criteria for treatment with spironolactonespironolactone
New York heart Association class 3-4New York heart Association class 3-4 Left ventricular ejection fraction Left ventricular ejection fraction
<35%<35% Serum creatinine <2.5 mg/dLSerum creatinine <2.5 mg/dL Serum potassium <5 mmol/LSerum potassium <5 mmol/L Baseline treatment with ACE inhibitor Baseline treatment with ACE inhibitor
(or other vasodilator if ACE inhibitor (or other vasodilator if ACE inhibitor intolerance), loop diuretic, and intolerance), loop diuretic, and digoxin as indicateddigoxin as indicated
DigoxinDigoxin
Digoxin has a significant role in Digoxin has a significant role in improving symptoms and improving symptoms and rehospitalization raterehospitalization rate
No impact on the total and No impact on the total and cardiovascular mortalitycardiovascular mortality
Usually used only in severe CHF or in Usually used only in severe CHF or in patients who remain symptomatic patients who remain symptomatic with optimal treatmentwith optimal treatment
Digoxin is useful in CHF with atrial Digoxin is useful in CHF with atrial fibrillationfibrillation
DigoxinDigoxin
DIG trial DIG trial 6800 pts EF <45%6800 pts EF <45% 0.25 mg/day0.25 mg/day 22% reduction in hospitalisation22% reduction in hospitalisation No mortlity benefitNo mortlity benefit 28% RRR of death in post hoc 28% RRR of death in post hoc
analysisanalysis
NesiritideNesiritide
Identical to human BNPIdentical to human BNP Causing vasodilation and decrease Causing vasodilation and decrease
LV filling pressureLV filling pressure Decrease pulmonary capillary wedge Decrease pulmonary capillary wedge
pressurepressure Improves patients’ symptomsImproves patients’ symptoms Improvement in hemodynamics Improvement in hemodynamics
VMAC trial 5.8 mm of hg decrease on VMAC trial 5.8 mm of hg decrease on PCWPCW
NesiritideNesiritide
2 mcg/kg bolus infusion 0.01-0.03 2 mcg/kg bolus infusion 0.01-0.03 mcg/kg/min for 3 hrsmcg/kg/min for 3 hrs
Improved safety profile compared Improved safety profile compared with dobutamine with fewer with dobutamine with fewer arrhythmias and better outcomesarrhythmias and better outcomes
It should not be used in patients who It should not be used in patients who are overdiuresed, hypotensive, or are overdiuresed, hypotensive, or present with other signs of present with other signs of inadequate perfusion -inadequate perfusion -Worsening of Worsening of renal failure (45%)renal failure (45%)
InotropesInotropes
Inotropes: direct adrenergic agonists, Inotropes: direct adrenergic agonists, phosphodiesterase inhibitors, and phosphodiesterase inhibitors, and dopaminergic agonistsdopaminergic agonists
Inotropes improve short term Inotropes improve short term hemodynamics, they do not improve hemodynamics, they do not improve and in several cases may worsen long-and in several cases may worsen long-term survival term survival
Oral inotropic agents have resulted in Oral inotropic agents have resulted in excess mortality in patients with HFexcess mortality in patients with HF
AmiodaroneAmiodarone
Antiarrhythmic effectAntiarrhythmic effect Low dose amiodarone was safe and Low dose amiodarone was safe and
significantly reduced 2-year mortality significantly reduced 2-year mortality (33.5% vs 41.4%, p=0.02)(33.5% vs 41.4%, p=0.02)
in patients with moderate to severe HF in patients with moderate to severe HF (GESICA trial)(GESICA trial)
Another trial did not demonstrate Another trial did not demonstrate mortality benefit, either all-cause or mortality benefit, either all-cause or sudden death sudden death
AnticoagulationAnticoagulation
LVEF < 30%LVEF < 30% LV thrombusLV thrombus Atrial fibrillationAtrial fibrillation INR 2-3INR 2-3
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