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  • 9/21/15


    Congestive Heart Failure 2015

    JP Mehegan/ Mercy Cardiology


    n Cardiac failure; Congestive heart failure; Chronic heart failure (synonyms)

    n When the heart is unable to pump sufficiently and at the appropriate pressure to meet the bodies needs

    n Symptoms; dyspnea, edema, fatigue; activity intolerance


    Types of Heart Failure

    n Systolic ; heart failure with abnormal LV function; ejection fraction < 40%

    n Diastolic; heart failure with normal LV systolic function and abnormal cardiac relaxation (diastolic function); 50%

    n Other; valvular, ischemia, MI, constriction/pericardial disease

    The Problem (USA) 5,000,000 patients 6,500,000 hospital days / year 300,000 deaths / year More than half of those diagnosed will be

    dead in 5 years 6% of health care budget (38 billion) Incidence doubling in last ten years

    Heart Failure Costs

    60% Inpatient care $23.1 billion

    39% Outpatient care

    $14.7 billion

    1% Transplants $270 million Total = $38.1 billion

    (5.4% of total healthcare costs)

    OConnell JB et al. J Heart Lung Transplant. 1994;13:S107-S112

    Stages in the evolutionof Heart Failure

    n A. HF risk factors; no documented heart disease or symptoms

    n B. Heart disease; no symptoms. Asymptomatic LV dysfunction

    n C. Prior or current symptomatic CHFn D. Refractory HF symptoms

    AHA / ACC HF guidelines 2005

  • 9/21/15


    Stages in Prevention and Treatment of Heart Failure

    n A. Treat risk factors, avoid toxins. ACE-In B. ACE-I, Beta blockersn C. ACE-I, Beta blockers, dig, diuretics,

    aldosterone antagonists, ARB, resynchronization (Bi-V pacing), new therapies

    n D. Ultrafiltration, inotrope therapy, VADs and transplant

    Classification of Functional Status; NYHA

    n 1. No physical limitationsn 2. Symptoms with moderate activity,

    exercise.n 3. Symptoms with mild activity; activities

    of daily livingn 4. Symptoms at rest

    Initial / Ongoing Evaluation

    n H&Pn Assess functional capacity (NYHA, 6 min

    walk)n Assess volume status: (edema, rales, jugular,

    hepatomegaly, body weight)n Lab assessment: routine: electrolytes, renal

    function, ECHO, X ray ,TSH, EKGn BNP

    Causes of Cardiomyopathy/ CHF

    n 135 Causes of cardiomyopathyn CAD; prior MI, diffuse ischemia (70%)n Hypertensionn Endocrine; diabetes, thyroidn Drugs/ Toxins; ETOH, cocaine, chemon Afib/ flutter; rate relatedn Infection, familial, nutritional, idiopathic

    B type natriuretic peptideBNP

    n Role in the emergency room70 yo with PND, orthopnea, edema and vascular congestion on CXR70 yo with COPD, wheezing, rales and edema, clear CXR

    n Role in the clinic

    Treatment Objectives

    n Increase Survivaln Improve LV functionn Improve symptoms/ Quality of Lifen Improve exercise capacityn Block neurohormonal changes and

    prevent progressive HFn CHF Trials App ($2.99)

  • 9/21/15


    Beta blocker

    Mineralocorticoid receptor


    Drugs That Reduce Mortality in Heart Failure With Reduced Ejection Fraction

    ACE inhibitor

    Angiotensin receptor blocker

    Drugs that inhibit the renin-angiotensin system have modest effects on


    Based on results of SOLVD-Treatment, CHARM-Alternative, COPERNICUS, MERIT-HF, CIBIS II, RALES and EMPHASIS-HF






    % D



    in M



    TreatmentPharmacologic Therapy

    nACE inhibitors/ARBs/Vasodilators

    nBeta BlockersnDiureticsn Digitalisn Spironolactone/ Eplerenome

    ACE-I. Clinical Effects

    n Improve symptomsnReduce remodeling / progressionnReduce hospitalizationn Improve survival

    ACE-i Practical Usen Start with low dosen Increase dose as toleratedn Renal function & serum K+ after 1-2

    weeksn Dose NOT determined by symptoms n Target randomized trial doses n Reduce diuretics if possible

    Mortality Reduction with ACE-i

    Study ACE-i Clinical SettingCONSENSUS (1987) Enalapril CHFSOLVD treatment Enalapril CHFAIRE Ramipril CHFVheft-II Enalapril CHFTRACE Trandolapril CHF SAVE Captopril LVD/MISMILE Zofenopril High risk HOPE (2000) Ramipril High risk

    ACE-i Dose (mg)

    Initial MaximumCaptopril 6.25 / 8h 50 / 8hEnalapril 2.5 / 12 h 10 to 20 / 12hFosinopril 5 to 10 / day 40 / dayLisinopril 2.5 to 5.0 / day 20 to 40 / dayQuinapril 10 / 12 h 40 / 12 hRamipril 1.25 to 2.5 / day 10 / day

    AHA / ACC HF guidelines 2005

  • 9/21/15


    ACE-i Adverse Effects

    nHypotensionnWorsening renal functionnHyperkalemianCough 5-10%(iron pill may prevent)nAngioedema (1/1000)nRash, ageusia, neutropenia (1-2%)nACE intolerant use ARB

    Angiotensin Receptor BlockersARBs

    n As added therapyn As alternative therapy (ACEi intolerant)n FDA approved; Valsartan 40 mg BID

    start, 160 mg BID targetn Candesartan; 4 mg QD start, 32 mg QD

    targetn Most commonly used ( not approved and

    underdosed), Losartan, target 150 mg QD

    Val-HeFT5010 patients

    18 years; EF 2.9 cm/m2

    ACE inhibitors, diuretics,digoxin, -blockers

    Valsartan40 mg bid titrated to

    160 mg bid

    Randomized to

    Receiving background therapy


    Cohn JN et al. Eur J Heart Fail. 2000;2:439-446.

    Effect of Valsartan on Combined Morbidity/Mortality Endpoint*

    Months3 6 9 12 15 18 21 24 270



    Probability of Event-

    Free Survival


    *All-cause mortality, sudden death with resuscitation, hospitalization for worsening heart failure, or therapy with IV inotropes or vasodilators. Cohn JN et al. N Engl J Med. 2001;345:1667-1675.



    P = 0.00913.2% Risk Reduction

    Reduction in Combined Morbidity/Mortality Endpoint* with Valsartan (No ACE-I Subgroup)

    Hazard ratio (Cox model) : 0.560*First morbid event, including death or hospitalization

    Time Since Randomization (months)





    0 3 6 9 12 15 18 21 24 27 30

    P < 0.00144.0% Risk reduction

    Valsartan, n=185

    Placebo, n=181

    Probability of Event-

    Free probability

    Maggioni et al. J Am Coll Cardiol 2002;40:1414-21


    7,601 patients with heart failure 3 Individual component randomized trials with the ARB candesartan (4

    or 8 mg/day, titrated to target dose of 32 mg) or placebo

    CHARM Added Patients with LVEF

  • 9/21/15



    At risk, n Placebo 1272 1017 852 736 338 Candesartan 1276 1074 914 793 395

    Primary Outcome CV Death or CHF Hospitalization

    CHARM Added

    1 2 3 Time, yr






    50 Placebo

    Candesartan %


    HR 0.85 (95% CI: 0.75, 0.96), p = 0.011 Adjusted HR = 0.85, p = 0.010

    483 (37.9%) 538 (42.3%)

    15% risk reduction


    NNT = 23

    -Adrenergic Blockers Mechanism of action

    n Increase Density of 1 receptorsn Inhibit cardiotoxicity of catecholaminesn Block Neurohormonal activationn HRn Antiischemicn Antihypertensive Antiarrhythmic Antioxidant, Antiproliferative

    -Adrenergic Blockers Clinical Effects

    n Improve symptoms (only long term)n Reduce remodeling / progressionn Improve LV systolic functionn Reduce hospitalizationn Reduce sudden deathn Improve survival

    -Adrenergic Blockers When to start

    n Patient stablen Not volume overloadedn No need for i.v. inotropic drugsn Stable dose of ACEi /Diuretic/ Dig

    -Adrenergic Blockers Contraindications

    n Asthma (not COPD)n AV blockn Symptomatic hypotension /

    Bradycardia n PVD and Diabetes are NOT


    -Adrenergic Blocker Adverse Effects

    n Hypotensionn Fluid retention / worsening heart failuren Fatiguen Bradycardia / heart block

    n Reduce dosen Consider cardiac pacingn DONT GIVE UP

  • 9/21/15


    -Adrenergic Blockers Dose (mg)

    Initial TargetBisoprolol 1.25 / 24h 10 / 24hCarvedilol 3.125 / 12h 25 / 12h

    Carvedilol XL 10/ 24h 80/24hMetoprolol succinnate 12.5-25 / 24h 200 / 24h

    Start Low, Increase SlowlyIncrease the dose every 2 - 4 weeks

    35% ReductionIn death

    Carvedilol Effect on Survival

    What is Target Dose?

    What is Target Dose

    Which Agent Should We Use?n Substantial differences in BetaBlocking Agents

    n Beta-1 Selectivityn Alpha-1 blockaden Ancillary Properties

    nAntioxidant nEndothelin regulation

    COMETCarvedilol vs Metoprolol Tartrate

    n 5.7%mortalityn reduction

  • 9/21/15


    Digitalis. Clinical Effects

    n Improve symptoms and measured exercise

    n Reduction in hospitalization for CHFn Does not improve survival

    DIG trial



    N Engl J Med 1997;336:525

    Digitalis. Indications

    In combination with ACE-i + diuretics if persisting symptoms

    AF, to slow AV conduction

    Dose 0.125 to 0.250 mg / day

    AHA / ACC Guidelines 2005

    Diuretics. Indications

    1.Symptomatic HF, with fluid retention Edema Dyspnea Lung Rales Jugular distension Hepatomegaly Pulmonary edema (Xray)

    Loop Diuretics / Thiazides. Practical Use