GUIAS PARA EL MANEJO DEL FALLO CARDIACO RAFAEL E. CALDERON,MD. CARDIOLOGIA DE TRANSPLANTE Y FALLO...

GUIAS PARA EL MANEJO DEL GUIAS PARA EL MANEJO DEL FALLO CARDIACOFALLO CARDIACO

RAFAEL E. CALDERON,MD.RAFAEL E. CALDERON,MD.CARDIOLOGIA DE TRANSPLANTE Y CARDIOLOGIA DE TRANSPLANTE Y

FALLO CARDIACOFALLO CARDIACO

OCTUBRE DEL OCTUBRE DEL 20022002

Cost* of Heart Failure to Cost* of Heart Failure to SocietySociety

Home health/Other medical durables

Indirect costs

Healthcare providers

Drugs

Hospital/Nursing home

AHA. 2000 Heart and Stroke Statistical Update

*Direct and indirect costs in billions of $; estimated for year 2000

15.5

2.2

2.2

1.5

1.1

$22.5 billion

Predisposing FactorsPredisposing Factors

HF

Valvular Valvular diseasediseaseEnvironmentEnvironment

alal

CardiomyopathCardiomyopathyy

GeneticGeneticUnknownUnknownInfectionsInfections

MIMI

HTNHTN

HTNHTN

MetabolicMetabolic(Diabetes)(Diabetes)

Toxins/Toxins/drugsdrugs(EtOH)(EtOH)

AgAgee

HFSA. Pharmacotherapy 2000;20:495

Risk Factors, Ischemia, and Heart Failure in the Cardiovascular

Continuum

Adapted with permission from Dzau V, Braunwald E. Am Heart J 1991;121:1244

Risk factors•Hyperlipidemia•HTN•Diabetes•Insulin resistance

AtherosclerosisLVH

CAD

Myocardial ischemia

Coronarythrombosis

MI

Neurohormonalactivation

Loss ofmuscle

Arrhythmia

Suddendeath

Remodeling

Ventricular

dilation

HF

Death

Pathophysiologic Effects of Angiotensin II

Contractility

Activate SNS

Aldosterone

Vasopressin

Endothelin

Ang II

Myocyte

growth

Vascular smooth muscle growth

Collagen

Superoxide

production

Platelet aggregation

PAI-1/ thrombos

is

Remodeling

Abnormal vasoconstriction

Guide for Heart Failure TherapyGuide for Heart Failure Therapy

• Slow progression of underlying disease(s)Slow progression of underlying disease(s)

• Improve hemodynamicsImprove hemodynamics

• Improve neurohormonal profileImprove neurohormonal profile

• Prevent sudden deathPrevent sudden death

• Decrease symptomatic arrhythmiasDecrease symptomatic arrhythmias

• Relieve symptoms and improve exercise toleranceRelieve symptoms and improve exercise tolerance

• Decrease ER visits, hospitalizations, and costsDecrease ER visits, hospitalizations, and costs

HFSA. Pharmacotherapy 2000;20:495

GoalGoal: : Prolong life and improve its Prolong life and improve its qualityquality

Objectives:Objectives:

Why Symptom Relief is Not Why Symptom Relief is Not EnoughEnough

Heart failure is more than a symptomatic diseaseHeart failure is more than a symptomatic disease

Produces symptoms, limits functional capacity, and Produces symptoms, limits functional capacity, and impairs quality of lifeimpairs quality of life

Heart failure is a progressive diseaseHeart failure is a progressive disease

Worsening symptoms and clinical deterioration, Worsening symptoms and clinical deterioration, repeated hospitalization, and deathrepeated hospitalization, and death

Death occurs frequently even in the presence of Death occurs frequently even in the presence of minimal symptoms or the absence of progressive minimal symptoms or the absence of progressive symptomssymptoms

Symptoms do not always correspond with ejection Symptoms do not always correspond with ejection fractionfraction

Evolution of Drug Therapies for Evolution of Drug Therapies for CHFCHF

18th Century

19th Centur

y1960s 1970s-1980s 1980s 1990s

•Digitalis •Weak diuretic

s

•Thiazides and

furosemide

•Vasodilators•IV inotropics

•ACE inhibitors

•Beta-blockers –Potential role for Angiotensin II antagonists–Aldosterone antagonists

Systemic Effects of RAS Activation in CHF

SOLVD-Prevention (Class I–II)4

n=4228trend toward death

60

Schematic Representation of Mortality

in Heart Failure Patients

Mortality rate

(%)

V-HeFT II (Class II–III)2

n=804 trend toward death

6 12 18 24 30 36 42 48 54

0

20

40

60 CONSENSUS I (Class IV)1

n=25327% mortality

P=0.003

SOLVD-Treatment (Class II–III)3

n=256916% mortality

P=0.0036

28% mortalityP=0.016

1CONSENSUS Trial Study Group. N Engl J Med 1987;316:1429; 2Cohn JN et al. N Engl J Med 1991;325:303;3SOLVD Investigators. N Engl J Med 1991;325:293; 4SOLVD Investigators. N Engl J Med 1992;327:685

Months

0

ACE Inhibitors in CHF:ACE Inhibitors in CHF: Summary of Key PointsSummary of Key Points

• Consistent evidence that Consistent evidence that neurohormonal blockade alters natural neurohormonal blockade alters natural history of CHFhistory of CHF

• ACE inhibitors improve survival across ACE inhibitors improve survival across entire heart failure spectrum - mild, entire heart failure spectrum - mild, moderate, severemoderate, severe

• Ace inhibitors delay progression of Ace inhibitors delay progression of asymptomatic LV dysfunction to overt asymptomatic LV dysfunction to overt CHFCHF

The Case for ß-Blockade in Heart The Case for ß-Blockade in Heart FailureFailureNeurohormonal activation underlies disease Neurohormonal activation underlies disease progression and provides basis for treatment progression and provides basis for treatment selectionselection

Weight of data for Weight of data for ß-blockade equals or exceeds that of ACE inhibitors

ß-Blockade is added to ACE inhibitors for more complete neurohormonal blockade

Carvedilol blocks ß1-, ß2-, and 1-receptors and is the only agent with ß-blocking properties approved and formulated for use in heart failure

ß-Blockers in Heart Failure:ß-Blockers in Heart Failure: Key Clinical TrialsKey Clinical Trials

US Carvedilol(n = 1094)

TRIAL

MERIT-HF(N = 3718)

CIBIS II(n = 2647)

Copernicus(n = 2289)

Carvedilol

DRUG

Metropolol

Bisoprolol

Carvedilol

65%(P <0.001)

RISK REDUCTION / TOTAL MORTALITY

34%(P = 0.0062)

33%(P <0.0001)

35%(P = 0.0014)

50-100 mg

TARGET DAILY DOSE

200 mg

10 mg

50 mg

P=0.00003Risk reduction: 38%

Perc

en

t of

pati

en

ts

Months of follow-up0 3 6 9 12 15 18 21

20

15

5

0

10

MERIT-HF MERIT-HF Cardiovascular MortalityCardiovascular Mortality MERIT-HF MERIT-HF Cardiovascular MortalityCardiovascular Mortality

MERIT-HF Study Group. Lancet. 1999;353:2001-2007.

Placebo

TOPROL-XLRisk reduction: 38%P = .00003

MERIT-HFMERIT-HFSudden Sudden DeathDeath

% of patient

s

Months of follow-up3 6 9 12 15 18 21

12

9

3

6

Placebo

TOPROL-XLRisk reduction: 41% P = .0002

MERIT-HF Study Group. Lancet. 1999;353:2001-2007.

DIG Study: Effect of Digoxin vs DIG Study: Effect of Digoxin vs Placebo on Mortality in Patients With Placebo on Mortality in Patients With CHF and LVEF CHF and LVEF 45% 45%

0

10

20

30

40

50

0 4 8 12 16 20 24 28 32 36 40 44 48 52

The Digitalis Investigation Group. N Engl J Med 1997;336:525-533.

Placebo

Digoxin

P=0.80

RADIANCE: Effect of Digoxin Withdrawal in RADIANCE: Effect of Digoxin Withdrawal in Patients Optimally Treated With Patients Optimally Treated With ACEIsACEIs

0

0.05

0.1

0.15

0.2

0.25

0.3

0 20 40 60 80 100Days after randomization

Probability of

worsening heart failure

• Risk of Risk of deterioration deterioration 6-fold 6-fold

Exercise Exercise tolerancetolerance

Ejection Ejection fractionfraction

Quality of Quality of lifelife

Packer M, et al. N Engl J Med 1993;329:1-7.

Placebo (n=93)

Digoxin (n=85)

P<0.01

RALES: Aldosterone Receptor Blockade RALES: Aldosterone Receptor Blockade Improves Outcomes in Severe Heart Improves Outcomes in Severe Heart FailureFailure

0.4

0.5

0.6

0.7

0.8

0.9

1

0 3 6 9 12 15 18 21 24 27 30 33 36

Months

Probability of Survival

(% )

RALES=Randomized Aldactone Evaluation Study Pitt B, et al N Engl J Med 1999;341:709-17

Spironolactone

Placebo

Valsartan in Heart Valsartan in Heart Failure Trial (Val-Heft)Failure Trial (Val-Heft)

• Ace inhibitors are effective treatment for HF, post-MI, Ace inhibitors are effective treatment for HF, post-MI, diabetic nephropathy, and atherosclerosis, but do not diabetic nephropathy, and atherosclerosis, but do not fully suppress RAASfully suppress RAAS

• The RAAS exerts deleterious effects on the The RAAS exerts deleterious effects on the development and progression of HFdevelopment and progression of HF

• Addition of ARBs to usual therapy, including ACE Addition of ARBs to usual therapy, including ACE inhibitors, is rational therapeutic approachinhibitors, is rational therapeutic approach

• ARBs inhibit biologic effects of Ang II more completely ARBs inhibit biologic effects of Ang II more completely than ACE inhibitorsthan ACE inhibitors

• ARBs potentially increase ATARBs potentially increase AT22 receptor stimulation receptor stimulation resulting in increased bradykinin and NO productionresulting in increased bradykinin and NO production

0.730

0.769

0.807

0.846

0.884

0.923

0.961

1.000

0 3 6 9 12 15 18 21 24 27

Heart Failure Heart Failure HospitalizationsHospitalizations

0

65

70

75

80

85

90

95

0

Cohn JN. AHA 2000

3 6 9 12 15 18 21 24 27

Valsartan Placebo

100

Months

Eve

nt-f

ree

Pro

babi

lity

P< 0.00001RR=27.5 %

General Measures for the General Measures for the Management of Heart Management of Heart FailureFailure

Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in heart FailureAm J Cardiol. 1999;83 (Suppl 2A): 1A-39A

Gottipaty et al: Gottipaty et al: Proportional Mortality Increase Proportional Mortality Increase

• VEST study analysisVEST study analysis

• NYHA Class II-IV NYHA Class II-IV patientspatients

• 3,654 ECGs digitally 3,654 ECGs digitally scannedscanned

• Age, creatinine, LVEF, Age, creatinine, LVEF, heart rate, and QRS heart rate, and QRS duration found to be duration found to be independent predictors independent predictors of mortality at 1 yearof mortality at 1 year

• Relative risk of widest Relative risk of widest QRS group 5x greater QRS group 5x greater than narrowestthan narrowest

QRS Variability in QRS Variability in Congestive Heart Failure: Congestive Heart Failure:

Pts with QRS 130

msec

Pts with QRS <

130 msecHFSA Sept 2001HFSA Sept 2001

Should QRS Criteria for Cardiac Should QRS Criteria for Cardiac Resynchronization Therapy Be Resynchronization Therapy Be

Expanded? (n = 31)Expanded? (n = 31)

Aranda, et alAranda, et al

Multicenter InSync Randomized Multicenter InSync Randomized Clinical EvaluationClinical Evaluation

Results of a Randomized, Double-Blind, Results of a Randomized, Double-Blind, Controlled Trial to Assess Cardiac Controlled Trial to Assess Cardiac

ResynchronizationResynchronization Therapy in Heart Failure Patients Therapy in Heart Failure Patients

Presented by William T. Abraham, MD Presented by William T. Abraham, MD For the MIRACLE Investigators at theFor the MIRACLE Investigators at the

Late Breaking Clinical Trials II Session,Late Breaking Clinical Trials II Session,American College of CardiologyAmerican College of CardiologyOrlando, FL; March 20, 2001Orlando, FL; March 20, 2001

Unanswered QuestionsUnanswered Questions

• Which subset of patients can benefit from Which subset of patients can benefit from biventricular pacing?biventricular pacing?

• What are the long-term hemodynamic and What are the long-term hemodynamic and structural consequences of CRT?structural consequences of CRT?

• Is there potential to increase ischemic Is there potential to increase ischemic burden in patients with ischemic burden in patients with ischemic cardiomyopathy?cardiomyopathy?

• Will cardiac resynchronization therapy Will cardiac resynchronization therapy allow for increased use of beta-blocker allow for increased use of beta-blocker therapy in patients with heart failure?therapy in patients with heart failure?

RecommendationsRecommendations

• Class I: There is evidence and/or general agreement Class I: There is evidence and/or general agreement that a given procedure/therapy is useful and that a given procedure/therapy is useful and effective.effective.

• Class II: There is conflicting evidence and/or a Class II: There is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy divergence of opinion about the usefulness/efficacy of performing the procedure/therapyof performing the procedure/therapy– Class IIa: Weight of evidence/opinion is in favor of Class IIa: Weight of evidence/opinion is in favor of

usefulness/efficacy.usefulness/efficacy.– Class IIb: Usefulness/efficacy is less well established by Class IIb: Usefulness/efficacy is less well established by

evidence/opinion.evidence/opinion.• Class III: There is evidence and/or general agreement Class III: There is evidence and/or general agreement

that procedure/therapy is not useful/effective and in that procedure/therapy is not useful/effective and in some cases may be harmfulsome cases may be harmful..

Levels of EvidenceLevels of Evidence

• Level A: Level A: The data was derived from multiple The data was derived from multiple randomized clinical trialsrandomized clinical trials

• Level B: Level B: Data were derived from single Data were derived from single randomized trial or nonrandomized studiesrandomized trial or nonrandomized studies

• Level C: Level C: Consensus of opinionConsensus of opinion

Clinical AssessmentClinical Assessment

• Complete history (Class I Level of evidence C): Complete history (Class I Level of evidence C): comorbid conditions, cardiotoxic agents, comorbid conditions, cardiotoxic agents, STD’s, magnitude and duration of symptoms STD’s, magnitude and duration of symptoms and family historyand family history

• Physical exam (Class I Level of evidence C): Physical exam (Class I Level of evidence C): Jugular venous pressure as ongoing Jugular venous pressure as ongoing assessment of volume status and Sassessment of volume status and S33

• Signs of hypoperfusion narrow pulse pressure, Signs of hypoperfusion narrow pulse pressure, cool extremities, altered mentation, Cheynes-cool extremities, altered mentation, Cheynes-Stokes respiration, resting tachycardia.Stokes respiration, resting tachycardia.


• Laboratory work upLaboratory work up– CBC, U/A, SMA 20, TSH, CXR and 12 lead EKG (Class CBC, U/A, SMA 20, TSH, CXR and 12 lead EKG (Class

I Level of evidence C)I Level of evidence C)– Serial monitoring of electrolytes and renal function Serial monitoring of electrolytes and renal function

(Class I Level of evidence C)(Class I Level of evidence C)– Screening for hemochromatosis, ANA levels, Screening for hemochromatosis, ANA levels,

rheumatoid factor, urinary vanillylmandelic acid and rheumatoid factor, urinary vanillylmandelic acid and metanephrines in selected patients (Class IIa Level metanephrines in selected patients (Class IIa Level of evidence C) of evidence C)

– HIV status HIV status (Class IIb Level of evidence C)(Class IIb Level of evidence C)– Routine measurement of circulating levels of Routine measurement of circulating levels of

norepinephrine or endothelin (Class III Level of norepinephrine or endothelin (Class III Level of evidence C)evidence C)

– Routine Holter monitoring or signal averaged Routine Holter monitoring or signal averaged electrocardiography (Class III Level of evidence C)electrocardiography (Class III Level of evidence C)


• Two-dimensional echocardiogram Two-dimensional echocardiogram with Doppler flow. Single most with Doppler flow. Single most useful diagnostic test. useful diagnostic test. – Evaluation of LV function and other Evaluation of LV function and other

structural heart disease (Class I Level of structural heart disease (Class I Level of evidence C)evidence C)

– Asymptomatic first degree relatives of Asymptomatic first degree relatives of idiopathic DCMP patients (Class IIa Level of idiopathic DCMP patients (Class IIa Level of evidence C)evidence C)

– Repeat measurement of EF in patients with Repeat measurement of EF in patients with change in clinical status (Class IIa Level of change in clinical status (Class IIa Level of evidence C)evidence C)

Clinical AssessmentClinical Assessment• Functional capacity assessment during Functional capacity assessment during

initial and follow up visitsinitial and follow up visits– Ability to perform routine and desired ADL’s (Class I Ability to perform routine and desired ADL’s (Class I

Level of evidence C)Level of evidence C)– Maximal exercise testing with measurement of Maximal exercise testing with measurement of

respiratory gas exchange and/or blood oxygen respiratory gas exchange and/or blood oxygen saturation to help determine whether HF is cause of saturation to help determine whether HF is cause of exercise limitation when the contribution of HF is exercise limitation when the contribution of HF is uncertain (Class IIa Level of evidence C)uncertain (Class IIa Level of evidence C)

– Maximal exercise testing with measurement of Maximal exercise testing with measurement of respiratory gas exchange to identify high risk patients respiratory gas exchange to identify high risk patients who are candidates for cardiac transplantation or other who are candidates for cardiac transplantation or other advanced treatments (Class IIa Level of evidence B)advanced treatments (Class IIa Level of evidence B)

– Maximal exercise testing with measurement of Maximal exercise testing with measurement of respiratory gas exchange to facilitate prescription of respiratory gas exchange to facilitate prescription of exercise program (Class IIb Level of evidence C)exercise program (Class IIb Level of evidence C)


• Noninvasive testingNoninvasive testing– Noninvasive imaging to detect ischemia Noninvasive imaging to detect ischemia

and viability in patients with known CAD and viability in patients with known CAD and no angina who are being and no angina who are being considered for revascularization considered for revascularization (Class (Class IIa Level of evidence C)IIa Level of evidence C)

– Noninvasive imaging to define the Noninvasive imaging to define the likelihood of CAD in patients with LV likelihood of CAD in patients with LV dysfunction dysfunction (Class IIb Level of evidence C)(Class IIb Level of evidence C)


• Cardiac Catheterization with coronary Cardiac Catheterization with coronary arteriographyarteriography– Patients with angina who are candidates for Patients with angina who are candidates for

revascularization revascularization (Class I Level of evidence B)(Class I Level of evidence B)– Patients with chest pain who have not had Patients with chest pain who have not had

evaluation of their coronary anatomy and who evaluation of their coronary anatomy and who have no contraindications to coronary have no contraindications to coronary revascularization revascularization (Class IIb Level of evidence C)(Class IIb Level of evidence C)

– Patients with known or suspected CAD but Patients with known or suspected CAD but without angina who are candidates for without angina who are candidates for revascularization revascularization (Class IIb Level of evidence C)(Class IIb Level of evidence C)

– Repeat study or repeat noninvasive testing for Repeat study or repeat noninvasive testing for ischemia in patients for whom CAD has been ischemia in patients for whom CAD has been previously excluded as cause of LV dysfunction previously excluded as cause of LV dysfunction (Class III Level of evidence C)(Class III Level of evidence C)


• Endomyocardial Biopsy overall Endomyocardial Biopsy overall usefulness is unclearusefulness is unclear– Patients suspected of having inflammatory or Patients suspected of having inflammatory or

infiltrative disorder of the heart (Class IIb Level of infiltrative disorder of the heart (Class IIb Level of evidence C)evidence C)

– Used to confirm disorders that may disqualify a Used to confirm disorders that may disqualify a patient for transplant (amyloidosis) or identify patient for transplant (amyloidosis) or identify giant-cell myocarditis which due to rapid giant-cell myocarditis which due to rapid progression and poor response to therapy progression and poor response to therapy mandates immediate transplantation. mandates immediate transplantation.

– Routine evaluation of patients with HF (Class III Routine evaluation of patients with HF (Class III Level of evidence C)Level of evidence C)

Staging of HFStaging of HF

• A new approach that emphasized both the A new approach that emphasized both the evolution and progression of HFevolution and progression of HF

• It reliably and objectively identifies patients It reliably and objectively identifies patients in the course of their disease in the course of their disease

• Links treatments that are appropriate at Links treatments that are appropriate at each stage of HFeach stage of HF

• It is intended to complement It is intended to complement not not substitute substitute NYHA, which subjectively gauges severity of NYHA, which subjectively gauges severity of symptomssymptoms

Staging of HFStaging of HF

Staging of HF and Staging of HF and TherapyTherapy

Stage A of HF and Stage A of HF and TherapyTherapy

• High risk of developing HF.High risk of developing HF.– Control systolic and diastolic BP Control systolic and diastolic BP (Class I Level of (Class I Level of

evidence A)evidence A)– Adequate control of DM. (not yet shown to reduce Adequate control of DM. (not yet shown to reduce

subsequent HF)subsequent HF)– Treatment of lipid disorders in accordance with Treatment of lipid disorders in accordance with

guidelines as patients with atherosclerotic disease guidelines as patients with atherosclerotic disease are likely to develop HF (Class I Level of evidence B) are likely to develop HF (Class I Level of evidence B)

– Treat Thyroid disease Treat Thyroid disease (Class I Level of evidence C)(Class I Level of evidence C)

– Periodic evaluation for signs and symptoms of Periodic evaluation for signs and symptoms of HF HF (Class I Level of evidence C) (Class I Level of evidence C)

Stage A of HF and Stage A of HF and TherapyTherapy– Avoidance of cardiotoxic agents and behaviors Avoidance of cardiotoxic agents and behaviors

such as smoking, illicit drug use and alcohol such as smoking, illicit drug use and alcohol consumption.consumption.(Class I Level of evidence C)(Class I Level of evidence C)

– Ionizing radiation to mediastinum and Ionizing radiation to mediastinum and chemotherapeutic agents such as anthracyclines, chemotherapeutic agents such as anthracyclines, high dose cyclophosphamide and the monoclonal high dose cyclophosphamide and the monoclonal agent trastuzumab.agent trastuzumab.

– Control ventricular rate of tachyarrhythmias Control ventricular rate of tachyarrhythmias (Class (Class I Level of evidence B)I Level of evidence B)

– ACE inhibition in patients with history of ACE inhibition in patients with history of atherosclerotic vascular disease, DM, HBP and atherosclerotic vascular disease, DM, HBP and associated cardiovascular risk factors associated cardiovascular risk factors (Class I Level (Class I Level of evidence B)of evidence B)

Stage B of HF and Stage B of HF and TherapyTherapy

• LV dysfunction without HF symptoms.LV dysfunction without HF symptoms.– Patients with AMI should receive thrombolytic or Patients with AMI should receive thrombolytic or

undergo PTCA to decrease risk of developing HF. ACEI undergo PTCA to decrease risk of developing HF. ACEI regardless of EF and even if ischemic episode is regardless of EF and even if ischemic episode is remote remote (Class I Level of evidence A)(Class I Level of evidence A) and /or beta- and /or beta-blocker regardless of EF blocker regardless of EF (Class I Level of evidence A)(Class I Level of evidence A) improve survival.improve survival.

– Long term use of ACEI has been shown to delay onset Long term use of ACEI has been shown to delay onset of HF symptoms in patients with low EF of HF symptoms in patients with low EF independently of MI or not independently of MI or not (Class I Level of evidence B)(Class I Level of evidence B)

– Beta blockers independent of whether the patient has Beta blockers independent of whether the patient has had MI should be given in low LVEF had MI should be given in low LVEF (Class I Level of (Class I Level of evidence B)evidence B)

Stage B of HF and Stage B of HF and TherapyTherapy

– Valve replacement or repair for patients Valve replacement or repair for patients with hemodynamically significant stenosis with hemodynamically significant stenosis or regurgitation or regurgitation (Class I Level of evidence B)(Class I Level of evidence B)

– Long term treatment with vasodilators in Long term treatment with vasodilators in severe aortic regurgitation has not been severe aortic regurgitation has not been shown to reduce risk of HF or death shown to reduce risk of HF or death (Class (Class IIb Level of evidence B)IIb Level of evidence B)

– Treatment with digoxin in asymptomatic Treatment with digoxin in asymptomatic patient with LV dysfunction who are in sinus patient with LV dysfunction who are in sinus rhythm is not recommended rhythm is not recommended (Class III Level (Class III Level of evidence C)of evidence C)

Stage C of HF and TherapyStage C of HF and Therapy

• LV dysfunction with current or prior LV dysfunction with current or prior symptoms.symptoms.– Sodium restriction.Sodium restriction.– Daily weight.Daily weight.– Influenza and pneumococcal vaccination.Influenza and pneumococcal vaccination.– Physical activity exercise program. Physical activity exercise program. (Class IIa Level of (Class IIa Level of

evidence A)evidence A)

– Avoidance of NSAIDs (including COX2), calcium channel Avoidance of NSAIDs (including COX2), calcium channel blockers ( except amlodipine) and antiarrhythmic agents blockers ( except amlodipine) and antiarrhythmic agents (except amiodarone). (except amiodarone). (Class I Level of evidence B)(Class I Level of evidence B)

– Monitor potassium (3.8-5.2mmol per L) and magnesium.Monitor potassium (3.8-5.2mmol per L) and magnesium.– Patient education and close supervision.Patient education and close supervision.

Stage C of HF and Stage C of HF and TherapyTherapy

Stage C of HF and Stage C of HF and TherapyTherapy• Diuretics. For fluid retention. (Class I Diuretics. For fluid retention. (Class I

Level of evidence A)Level of evidence A)– Inhibit reabsorption of sodium or chloride at Inhibit reabsorption of sodium or chloride at

specific sites in the renal tubule.specific sites in the renal tubule.– Loop diuretics excrete up to 20-25% Na, enhance Loop diuretics excrete up to 20-25% Na, enhance

free water clearance and remain effective unless free water clearance and remain effective unless severe renal impairment.severe renal impairment.

– No long term studies effects on morbidity and No long term studies effects on morbidity and mortality are not knownmortality are not known

– Produce symptomatic relief more rapidly than Produce symptomatic relief more rapidly than any other drug.any other drug.

– Risk of use is electrolyte depletion, hypotension Risk of use is electrolyte depletion, hypotension and azotemia.and azotemia.


• ACE inhibitors. (Class I Level of evidence ACE inhibitors. (Class I Level of evidence A)A)– Not only interferes with RAS but potentates action of Not only interferes with RAS but potentates action of

kinins and kinin-mediated prostaglandin.kinins and kinin-mediated prostaglandin.– Alleviate symptoms, improve clinical status, reduce Alleviate symptoms, improve clinical status, reduce

risk of death and of hospitalization.risk of death and of hospitalization.– Contraindicated if angioedema or pregnant .Contraindicated if angioedema or pregnant .– Fluid retention can blunt effects and fluid depletion Fluid retention can blunt effects and fluid depletion

can potentate adverse effects (Hypotension, can potentate adverse effects (Hypotension, hyperkalemia, renal failure)hyperkalemia, renal failure)

– Cough. All other causes must be excluded medication Cough. All other causes must be excluded medication withdrawn with improvement after 1-2 weeks and withdrawn with improvement after 1-2 weeks and reappearance after rechallenge with another ACEI.reappearance after rechallenge with another ACEI.

Stage C of HF and Stage C of HF and TherapyTherapy• Beta-blockers principally inhibit effects Beta-blockers principally inhibit effects

of sympathetic nervous system and of sympathetic nervous system and should be given to all patients with should be given to all patients with symptoms (Class I Level of evidence A)symptoms (Class I Level of evidence A)– Alleviate symptoms, improve clinical status, Alleviate symptoms, improve clinical status,

reduce risk of death and of hospitalization.reduce risk of death and of hospitalization.– Diuretics are needed to maintain sodium balance Diuretics are needed to maintain sodium balance

and prevent fluid retention that can accompany and prevent fluid retention that can accompany initiation of beta-blocker.initiation of beta-blocker.

– Should be given only if no or only minimal Should be given only if no or only minimal evidence of fluid retention and no recent use of evidence of fluid retention and no recent use of intravenous positive inotropic agent.intravenous positive inotropic agent.

Stage C of HF and Stage C of HF and TherapyTherapy• Beta-blockersBeta-blockers

– A patient who has been using medication for more A patient who has been using medication for more than 3 months and has acute decompensation should than 3 months and has acute decompensation should not be taken off medication and diuretics should be not be taken off medication and diuretics should be adjusted. If decompensation is cause due to adjusted. If decompensation is cause due to hypoperfusion then medication should be stopped and hypoperfusion then medication should be stopped and positive inotropic agent that doesn’t mediate its positive inotropic agent that doesn’t mediate its effects through beta receptor is preferred.effects through beta receptor is preferred.

– Side effects include fatigue, fluid Side effects include fatigue, fluid retention,bradychardia, heart block, and hypotension.retention,bradychardia, heart block, and hypotension.

– Should not be given to patients with hyperactive Should not be given to patients with hyperactive airway disease yet should be given to COPD patients.airway disease yet should be given to COPD patients.


• Digitalis (Class I Level of evidence A)Digitalis (Class I Level of evidence A)– Inhibits Na-K ATPaseInhibits Na-K ATPase

• In cardiac cells causing increased contractilityIn cardiac cells causing increased contractility• Vagal afferent fibers sensitize carotid baroreceptor Vagal afferent fibers sensitize carotid baroreceptor

which reduces sympathetic out flow of CNSwhich reduces sympathetic out flow of CNS• Kidney reduces renal tubular reabsorption of Na which Kidney reduces renal tubular reabsorption of Na which

leads to suppression of of renin secretionleads to suppression of of renin secretion

– Improves symptoms, exercise tolerance and Improves symptoms, exercise tolerance and quality of life yet little effect on mortalityquality of life yet little effect on mortality

– Dose should be of 0.125-0.25mg QD, without Dose should be of 0.125-0.25mg QD, without loading and lower if patient is over age 70, has loading and lower if patient is over age 70, has renal impairment or low lean body massrenal impairment or low lean body mass

– Serum levels are followed for purpose of toxicity Serum levels are followed for purpose of toxicity and not to guide therapyand not to guide therapy


• Spironolactone (Class IIa Level of Spironolactone (Class IIa Level of evidence B)evidence B)– Low doses reduced risk of mortality in patents Low doses reduced risk of mortality in patents

with current or recent class IV symptoms with current or recent class IV symptoms – Effects were most marked in those taking Effects were most marked in those taking

digitalis and beta blockersdigitalis and beta blockers– Role in mild to moderate HF not clear and use Role in mild to moderate HF not clear and use

cannot be recommendedcannot be recommended– Risk of hyperkalemia and painful Risk of hyperkalemia and painful

gynecomastiagynecomastia


• Angiotensin receptor blockerAngiotensin receptor blocker– Should not be considered superior or Should not be considered superior or

equivalent to ACEI (Class III Level of equivalent to ACEI (Class III Level of evidence B)evidence B)

– Added to therapy before a beta-blocker Added to therapy before a beta-blocker (Class III Level of evidence A)(Class III Level of evidence A)

– Should not be added to therapy if taking an Should not be added to therapy if taking an ACEI and beta-blockerACEI and beta-blocker

– Should be given if ACEI intolerant (Class IIa Should be given if ACEI intolerant (Class IIa Level of evidence A)Level of evidence A)

Stage C of HF and TherapyStage C of HF and Therapy• Hydralazine and nitrate combination should be Hydralazine and nitrate combination should be

given only if ACEI intolerant and patient on given only if ACEI intolerant and patient on beta-blocker, diuretic and digitalis (Class IIa beta-blocker, diuretic and digitalis (Class IIa Level of evidence B) and should no be added if Level of evidence B) and should no be added if ACEI in use (Class IIb Level of evidence B)ACEI in use (Class IIb Level of evidence B)

• Long term intermittent intravenous positive Long term intermittent intravenous positive inotropic therapy has been associated with inotropic therapy has been associated with increased mortality and should not be used increased mortality and should not be used (Class III Level of evidence C). Continuous (Class III Level of evidence C). Continuous infusion for palliation of stage D symptoms is infusion for palliation of stage D symptoms is Class IIb Level of evidence C yet is commonly Class IIb Level of evidence C yet is commonly used in patients awaiting transplant.used in patients awaiting transplant.

Stage D of HF and Stage D of HF and TherapyTherapy

• Refractory End stage HFRefractory End stage HF– Must be considered for specialized treatment Must be considered for specialized treatment

strategies, such as mechanical circulatory support, strategies, such as mechanical circulatory support, continuous inotropic therapy, transplantation (Class I continuous inotropic therapy, transplantation (Class I Level of evidence B), referral to a specialized HF Level of evidence B), referral to a specialized HF program (Class I Level of evidence A)program (Class I Level of evidence A) or hospice care.or hospice care.

– Control of fluid retention with increments of dose or Control of fluid retention with increments of dose or adding second diuretic (metolazonel). Increases in BUN adding second diuretic (metolazonel). Increases in BUN and creatinine are tolerated and should not guide and creatinine are tolerated and should not guide therapy. If refractant to diuretics ultrafiltration may be therapy. If refractant to diuretics ultrafiltration may be needed.Patients should not be discharged until needed.Patients should not be discharged until euvolemia is achieved. (Class I Level of evidence B)euvolemia is achieved. (Class I Level of evidence B)

– All previous stage class I recommendations (Class I All previous stage class I recommendations (Class I Level of evidence A,B and C)Level of evidence A,B and C)

Stage D of HF and Stage D of HF and TherapyTherapy

Patient SubgroupsPatient Subgroups

• Women are the majority of patients in general Women are the majority of patients in general population with HF yet are underrepresented in population with HF yet are underrepresented in most studies which doesn’t allow for treatment most studies which doesn’t allow for treatment conclusions to be made. Have diastolic conclusions to be made. Have diastolic dysfunction most often.dysfunction most often.

• HF is more common among black patients and HF is more common among black patients and progresses more rapidly and may derive less progresses more rapidly and may derive less benefit of ACEI. Almost 50% of Asians can benefit of ACEI. Almost 50% of Asians can develop cough related to ACEI. develop cough related to ACEI.

• HF is a disease of the elderly affecting 6-10% of HF is a disease of the elderly affecting 6-10% of population over age 65. Diastolic dysfunction is population over age 65. Diastolic dysfunction is a major cause. Diminished response to a major cause. Diminished response to diuretics ACEI and inotropic agents.diuretics ACEI and inotropic agents.

Diastolic DysfunctionDiastolic Dysfunction

Therapy of Diastolic Therapy of Diastolic DysfunctionDysfunction• Control systolic and diastolic BP (Class I Level of Control systolic and diastolic BP (Class I Level of

evidence A)evidence A)

• Control ventricular rate in atrial fibrillation (Class I Control ventricular rate in atrial fibrillation (Class I Level of evidence C)Level of evidence C)

• Diuretics to control pulmonary congestion and Diuretics to control pulmonary congestion and peripheral edema (Class I Level of evidence C)peripheral edema (Class I Level of evidence C)

• Coronary revascularization I patients with CAD in Coronary revascularization I patients with CAD in whom ischemia is judged to have effect on whom ischemia is judged to have effect on diastolic dysfunction (Class IIa Level of evidence C)diastolic dysfunction (Class IIa Level of evidence C)

Therapy of Diastolic Therapy of Diastolic DysfunctionDysfunction

• Restoration of sinus rhythm in atrial Restoration of sinus rhythm in atrial fibrillation (Class IIb Level of evidence C)fibrillation (Class IIb Level of evidence C)

• Use of beta blockers, ACEI, ARB, CCB in Use of beta blockers, ACEI, ARB, CCB in patients with controlled hypertension to patients with controlled hypertension to minimize symptoms of HF (Class IIb Level minimize symptoms of HF (Class IIb Level of evidence C)of evidence C)

• Digitalis to minimize symptoms of HF Digitalis to minimize symptoms of HF (Class IIb Level of evidence C)(Class IIb Level of evidence C)

Na H2OVasodilationHypertrophyCO

Treatment of CHF in the Year Treatment of CHF in the Year 20012001

Inactive Inactive Angio 1Angio 1OVERTURE

NEP

ANPBNP

NATRE-COR

Inotropes

DIG TRIALVESTPROMISEOPTIME-CHFPROVED

Bradykinin

NO EDRF

ACE

Brain

Catecholamines ADH

CIBIS IIMERIT-HFBESTCOPERNICUS

Positive EffectNeutral EffectUnknown EffectNegative Effect

Angio 2

SOLVDCONSENSUS IIATLASSAVE

Elite I, IIVal-HeFT

KidneyVascular

AldosteroneEndothelin

RALES

BPNaHypertrophyHR

• EECPEECP

• The CorCap (Acorn)The CorCap (Acorn)

• Resembles a net that is Resembles a net that is placed around and placed around and

attached to the heart.attached to the heart. Cardiology Today,October Cardiology Today,October

20022002

Cardiology today, october Cardiology today, october 2002.2002.

The EndThe End

GUIAS PARA EL MANEJO DEL FALLO CARDIACO RAFAEL E. CALDERON,MD. CARDIOLOGIA DE TRANSPLANTE Y FALLO...

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