heart failure: evaluation and treatment anecita fadol, phd, rn,fnp-bc nurse practitioner

Heart Failure: Evaluation and Treatment

Anecita Fadol, PhD, RN,FNP-BCAnecita Fadol, PhD, RN,FNP-BCNurse PractitionerNurse Practitioner

Department of CardiologyDepartment of CardiologyUT MD Anderson Cancer CenterUT MD Anderson Cancer Center

ObjectivesObjectives

• Identify the different types of cardiomyopathyIdentify the different types of cardiomyopathy

• Describe the pathophysiologic mechanism of Describe the pathophysiologic mechanism of cardiomyopathy/heart failurecardiomyopathy/heart failure

• Discuss diagnostic testing/procedures for heart Discuss diagnostic testing/procedures for heart failure diagnosisfailure diagnosis

• Discuss the clinical guidelines for the management Discuss the clinical guidelines for the management of heart failure.of heart failure.

Case ExamplesCase Examples

• A 16 year old male with a history of pneumonia. He A 16 year old male with a history of pneumonia. He was brought to the clinic by his mother because he was brought to the clinic by his mother because he did not seem to get better after 8 weeks since the did not seem to get better after 8 weeks since the initial flu like symptoms. Last night he had severe initial flu like symptoms. Last night he had severe fatigue and shortness of breath while brushing his fatigue and shortness of breath while brushing his teeth.teeth.

• A 63 year old female with a known history of A 63 year old female with a known history of breast cancer, treated with anthracycline-based breast cancer, treated with anthracycline-based chemotherapy 30 years ago. Recently, she noted chemotherapy 30 years ago. Recently, she noted progressively increasing shortness of breath with progressively increasing shortness of breath with exertion, PND and lower extremity swelling.exertion, PND and lower extremity swelling.

Cardiomyopathy and Heart FailureCardiomyopathy and Heart Failure

• Cardiomyopathy is a Cardiomyopathy is a weakening or deformity of weakening or deformity of the heart muscle that the heart muscle that causes decreased pumping causes decreased pumping force.force.

AHA, 2008a; DeMartinis et al, 2003; Hunt et al, 2005; Yahalom et al, 2005

Risk Factors for Cardiomyopathy/HFRisk Factors for Cardiomyopathy/HF• Major causes of CMP/HFMajor causes of CMP/HF

– Ischemic heart disease (e.g., coronary artery disease)Ischemic heart disease (e.g., coronary artery disease)– Nonischemic underlying diseases (e.g., hypertension, valvular heart Nonischemic underlying diseases (e.g., hypertension, valvular heart

disease)disease)• Risk factors for cardiomyopathy/HFRisk factors for cardiomyopathy/HF

– History of or active coronary artery diseaseHistory of or active coronary artery disease– Hypertension (75% of patients)Hypertension (75% of patients)– Genetic predisposition, congenital heart defectsGenetic predisposition, congenital heart defects– DiabetesDiabetes– Valvular heart diseaseValvular heart disease– Thyroid diseaseThyroid disease– HyperlipidemiaHyperlipidemia– Sleep apneaSleep apnea– Overweight (elevated body mass index [BMI])Overweight (elevated body mass index [BMI])– Sedentary lifestyleSedentary lifestyle– Advanced ageAdvanced age– ViralViral– Others (e.g., smoking, alcohol, illicit or therapeutic cardiotoxic drugs)Others (e.g., smoking, alcohol, illicit or therapeutic cardiotoxic drugs)

Chang, 2007; DeMartinis et al, 2003; Hunt et al, 2005

Non – ischemic CardiomyopathyNon – ischemic Cardiomyopathy

Heart Failure (HF) DefinitionHeart Failure (HF) Definition

A complex clinical syndrome in which the heart is A complex clinical syndrome in which the heart is incapable of maintaining a cardiac output adequate incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the to accommodate metabolic requirements and the venous return.venous return.

The Donkey Analogy The Donkey Analogy

Ventricular dysfunction limits a patient's ability to perform the Ventricular dysfunction limits a patient's ability to perform the routine activities of daily living…routine activities of daily living…

Epidemiology of HF in the USEpidemiology of HF in the US

• 5 million symptomatic patients in 5 million symptomatic patients in 2001; estimated 10 million in 2001; estimated 10 million in 203720371,21,2

• Incidence: about 550,000 new Incidence: about 550,000 new cases/yearcases/year22

• Prevalence is 1% between the Prevalence is 1% between the ages of 50 and 59 yearsages of 50 and 59 years33; ; progressively increasing to 10% progressively increasing to 10% over age 80over age 8044

1Adapted from Gilbert E. Rev Cardiovasc Med. 2002;3:S42-S47. 2American Heart Association. 2004 Heart and Stroke Statistical Update. 2003. 3Ho KKL et al. J Am Coll Cardiol. 1993;22:6A-13A. 4Rich M. J Am Geriatric Soc. 1997;45:968-974.

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Part I: Part I: Pathophysiology of Heart FailurePathophysiology of Heart Failure

1 Adapted from Cohn JN. N Engl J Med. 1996;335:490–498.2 He J, Ogden LG, Bazzano LA, et al. Risk Factors for Congestive Heart Failure in US Men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 2001, 161: 996-1002.

Pathologicremodeling

Low ejectionfraction Death

Symptoms:DyspneaFatigueEdema

Chronicheartfailure

• Neurohormonalstimulation

• Endothelial dysfunction

• Myocardial toxicity• Vasoconstriction• Renal sodium retention

Arrhythmia

Pump failure

Left ventricularinjury

Pathological Progression of CV Disease Pathological Progression of CV Disease 11

CAD

CM

HTN

Valvular Dz

Endothelial Dysfunction

Chemo

30%30%

70%70%

Diastolic DysfunctionDiastolic DysfunctionSystolic DysfunctionSystolic Dysfunction

(EF < 40%)(EF < 40%)(EF > 40 %)(EF > 40 %)

Left Ventricular DysfunctionLeft Ventricular Dysfunction• Systolic:Systolic: Impaired contractility/ejection Impaired contractility/ejection

– Approximately two-thirds of heart failure patients have systolic Approximately two-thirds of heart failure patients have systolic dysfunctiondysfunction11

• Diastolic:Diastolic: Impaired filling/relaxation Impaired filling/relaxation

1 Lilly, L. 1 Lilly, L. Pathophysiology of Heart DiseasePathophysiology of Heart Disease. Second Edition p 200. Second Edition p 200

Classification of HF: Comparison Between Classification of HF: Comparison Between ACC/AHA HF Stage and NYHA Functional ClassACC/AHA HF Stage and NYHA Functional Class

1Hunt SA et al. J Am Coll Cardiol. 2005;38:2101-2113. 2New York Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al. JAMA. 2002;287:890-897.

ACC/AHA HF Stage1

NYHA Functional Class2

A At high risk for HF but withoutstructural heart disease or symptomsof HF (eg, patients with HTN or CAD)

B Structural heart disease but withoutsymptoms of HF

C Structural heart disease with prior orcurrent symptoms of HF

D Refractory HF requiringspecialized interventions

I Asymptomatic

II Symptomatic with moderate exertion

IV Symptomatic at rest

III Symptomatic with minimal exertion

Asymptomatic

Symptomatic

Part II:Part II:Assessing Heart FailureAssessing Heart Failure

Cardiac AssessmentCardiac Assessment

• A comprehensive A comprehensive cardiac assessment cardiac assessment includes the following:includes the following:

– Patient historyPatient history

– Physical assessmentPhysical assessment

– Diagnostic testingDiagnostic testing

Cardiac Assessment: Diagnostic TestingCardiac Assessment: Diagnostic Testing

DeMartinis et al, 2003; Chang, 2007; Fadol, 2006; Hunt et al, 2005

• Follow-up: Assess signs and symptoms, functional capacity, body weight, understanding of treatment, compliance, exacerbating factors for HF

Initial diagnostic evaluation for HF patient

Echocardiogram (ECHO) Measures heart size, wall thickness/mobility, flow gradients, valvular function, LVEF

Electrocardiogram Assesses cardiac rhythm, conduction; can detect myocardial infarction, arrhythmias

Chest x-ray Detects heart enlargement, fluid around heart or lungs

Standard laboratory tests•Blood chemistry, urinalysis•Complete blood count (CBC) •Renal, liver, thyroid tests

•Blood urea nitrogen (BUN), creatinine, albumin (liver function), glucose (diabetes)

•CBC detects anemia, infection•Organ function as a contributing factor or resulting from HF

Cardiac enzymesCardiac markers

Creatinine kinase (CK, CK-MB), cardiac troponins I and T Brain natriuretic peptide (BNP)

Part III: Part III: Current Treatment Current Treatment

of Heart Failureof Heart Failure

The Vicious Cycle of The Vicious Cycle of Heart Failure ManagementHeart Failure Management

Chronic HFChronic HF

MD’s OfficeMD’s Office

Emergency Emergency RoomRoom

HospitalizationHospitalization

SOBSOB

WeightWeight

PO LasixPO LasixIV Lasix IV Lasix or Admitor Admit

Diurese & Diurese & HomeHome

Goals of Heart Failure TherapyGoals of Heart Failure Therapy

• Relieve heart failure symptomsRelieve heart failure symptoms– Improve overall clinical statusImprove overall clinical status– Stabilize acute episodes of decompensationStabilize acute episodes of decompensation

• Decrease morbidity and mortalityDecrease morbidity and mortality– Slow and/or reverse disease progressionSlow and/or reverse disease progression– Identify and treat reversible causes of LV Identify and treat reversible causes of LV

dysfunctiondysfunction

General Approach to TreatmentGeneral Approach to Treatment

• Determine etiology and/or precipitating factorsDetermine etiology and/or precipitating factors– Avoid drugs which may aggravate HFAvoid drugs which may aggravate HF

• Treat underlying disordersTreat underlying disorders– Anemia, hypo/hyperthyroidism, valvular diseaseAnemia, hypo/hyperthyroidism, valvular disease

– Revascularization or anti-ischemic therapy in patients with CAD Revascularization or anti-ischemic therapy in patients with CAD may reduce symptoms of HFmay reduce symptoms of HF

• Physical activity (low-intensity) if stablePhysical activity (low-intensity) if stable

• Restrict fluid (~2 L/day) and sodium intake (<1.5-2 g/day)Restrict fluid (~2 L/day) and sodium intake (<1.5-2 g/day)

Established Therapy:Established Therapy:Drugs with a mortalityDrugs with a mortality benefit in HFbenefit in HF

• Beta-blockersBeta-blockers• Angiotensin converting enzyme (ACE) inhibitors Angiotensin converting enzyme (ACE) inhibitors

– Angiotensin Receptor Blocker (Candesartan)Angiotensin Receptor Blocker (Candesartan)• Spironolactone or EplerenoneSpironolactone or Eplerenone• Isordil/HydralazineIsordil/Hydralazine

DigoxinDigoxin

• Mechanism of action:Mechanism of action: contractilitycontractility

• Inhibition of sodium/potassium ATPase pump which acts to Inhibition of sodium/potassium ATPase pump which acts to increase intracellular sodium-calcium exchange to increase increase intracellular sodium-calcium exchange to increase intracellular calcium leading to increased contractilityintracellular calcium leading to increased contractility

– NeurohormonalNeurohormonal• Blunt SNS activationBlunt SNS activation

• Increase vagal toneIncrease vagal tone– Slow conduction, prolong AV refractoriness, slowing Slow conduction, prolong AV refractoriness, slowing

ventricular response in atrial fibrillationventricular response in atrial fibrillation

Pharmacologic ManagementPharmacologic Management

DigoxinDigoxin

• Enhances inotropy of cardiac muscleEnhances inotropy of cardiac muscle

• Reduces activation of SNS and RAASReduces activation of SNS and RAAS

• Controlled trials have shown long-term digoxin therapy:Controlled trials have shown long-term digoxin therapy:– Reduces symptomsReduces symptoms– Increases exercise toleranceIncreases exercise tolerance– Improves hemodynamicsImproves hemodynamics– Decreases risk of HF progressionDecreases risk of HF progression– Reduces hospitalization rates for decompensated HFReduces hospitalization rates for decompensated HF– Does not improve survivalDoes not improve survival

DigoxinDigoxin

• Warnings/PrecautionsWarnings/Precautions– Acute myocardial infarction Acute myocardial infarction

– Acute myocarditis or amyloid cardiomyopathyAcute myocarditis or amyloid cardiomyopathy

– Correct electrolyte imbalances Correct electrolyte imbalances – Adjust dose in renal disease Adjust dose in renal disease

– Bradycardia Bradycardia

– Withdrawal in CHF patients may lead to recurrent CHF symptomsWithdrawal in CHF patients may lead to recurrent CHF symptoms

– Drug interactionsDrug interactions

– Digoxin toxicityDigoxin toxicity

Digitalis CompoundsDigitalis Compounds

Like the carrot placed in front of the donkeyLike the carrot placed in front of the donkey


DiureticsDiuretics

• Used to relieve fluid retentionUsed to relieve fluid retention

• Improve exercise toleranceImprove exercise tolerance

• Facilitate the use of other drugs indicated for heart failure Facilitate the use of other drugs indicated for heart failure

• Patients can be taught to adjust their diuretic dose based on Patients can be taught to adjust their diuretic dose based on changes in body weightchanges in body weight

• Electrolyte depletion a frequent complicationElectrolyte depletion a frequent complication

• Should never be used alone to treat heart failureShould never be used alone to treat heart failure

• Higher doses of diuretics are associated with increased Higher doses of diuretics are associated with increased mortalitymortality

DiureticsDiuretics• Diuretics and salt restriction are indicated in Diuretics and salt restriction are indicated in

patients with current or prior symptoms of HF and patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention reduced LVEF who have evidence of fluid retention (Class I; LOE C)(Class I; LOE C)– Use until euvolemic stage is achievedUse until euvolemic stage is achieved

– Continue to prevent recurrence of fluid retentionContinue to prevent recurrence of fluid retention

• Increase urinary sodium excretionIncrease urinary sodium excretion• Improve pulmonary and peripheral congestionImprove pulmonary and peripheral congestion

– Decrease preloadDecrease preload

• No long-term studies No long-term studies – Effects on morbidity and mortality are unknownEffects on morbidity and mortality are unknown

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult

http://www.acc.org/clinical/guidelines/failure/hf_index.htm

Dosing Oral DiureticsDosing Oral Diuretics



Dosing IV DiureticsDosing IV Diuretics



ACE inhibitorsACE inhibitors

• Mechanism of action:Mechanism of action: preload and afterloadpreload and afterload– Arterial and venous dilatationArterial and venous dilatation

• Reduces formation of Angiotension II (vasoconstrictor)Reduces formation of Angiotension II (vasoconstrictor)• Reduces breakdown of bradykinin (vasodilator)Reduces breakdown of bradykinin (vasodilator)

• Clinical Effects:Clinical Effects:– Improve symptomsImprove symptoms– Reduce remodeling / progressionReduce remodeling / progression– Reduce hospitalizationReduce hospitalization– Improve survivalImprove survival

Ace InhibitorsAce Inhibitors

• RecommendationsRecommendations– ACEIs are recommended for ACEIs are recommended for allall patients with current or prior patients with current or prior

symptoms of HF and symptoms of HF and reduced LVEFreduced LVEF , unless contraindicated , unless contraindicated (Class I; LOE A)(Class I; LOE A)

– ACEIs should be used in ACEIs should be used in allall patients with reduced LVEF and no patients with reduced LVEF and no symptoms of HF, even symptoms of HF, even if they have notif they have not experienced MI experienced MI (Class I; (Class I; LOE A)LOE A)

– ACEIs or ARBs can be beneficial in patients with HTN and LVH ACEIs or ARBs can be beneficial in patients with HTN and LVH and no symptoms of HF and no symptoms of HF (Class IIa; LOE B)(Class IIa; LOE B)



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Effect of ACE Inhibitors on SurvivalEffect of ACE Inhibitors on Survivalin Heart Failurein Heart Failure

SOLVD-P SOLVD-T CONSENSUS

NYHA Class Class I-II (N=4228) Class II-III (N=2569) Class IV (N=253)Treatment Enalapril Enalapril EnalaprilResults 8% 16% 27%(% reduction in all-cause mortality)

1The SOLVD Investigators. N Engl J Med. 1991;325:293-302. 2Cohn J et al. N Engl J Med. 1991;325:303-310. 3The CONSENSUS Trial Study Group. N Engl J Med. 1987;316;1429-1435.

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Enalapril

Hydralazine Isosorbide Dinitrate

Enalapril

Placebo

P<0.0036 P<0.003


ACEIACEI Initial DoseInitial Dose Maximum DoseMaximum Dose

Captopril Captopril 6.25 mg tid6.25 mg tid 50 mg tid50 mg tidEnalaprilEnalapril 2.5 mg bid2.5 mg bid 10-20 mg bid10-20 mg bidFosinoprilFosinopril 5-10 mg daily5-10 mg daily 40 mg daily40 mg dailyLisinoprilLisinopril 2.5-5 mg daily2.5-5 mg daily 20-40 mg daily20-40 mg dailyQuinaprilQuinapril 5 mg bid5 mg bid 20 mg bid20 mg bidRamiprilRamipril 1.25-2.5 mg daily1.25-2.5 mg daily 10 mg daily10 mg daily

TrandolaprilTrandolapril 1 mg daily1 mg daily 4 mg daily4 mg daily



Ace InhibitorsAce Inhibitors

• Contraindications:Contraindications:– HypersensitivityHypersensitivity

– Angioedema related to Angioedema related to previous treatment with previous treatment with ACEIACEI

– Hereditary angioedemaHereditary angioedema

– Bilateral renal artery Bilateral renal artery stenosisstenosis

– Pregnancy (2nd and 3rd Pregnancy (2nd and 3rd trimester)trimester)

• Warnings/Precautions: Warnings/Precautions: – Anaphylactic reactions can Anaphylactic reactions can

occuroccur

– Angioedema can occur at any Angioedema can occur at any time during treatment, especially time during treatment, especially after 1st doseafter 1st dose

– Careful BP monitoring with 1st Careful BP monitoring with 1st dose (hypotension)dose (hypotension)

• Captopril>Lisinopril>EnalaprilCaptopril>Lisinopril>Enalapril

– May cause hyperkalemia, rise in May cause hyperkalemia, rise in ScrScr

Principles of ACEI therapyPrinciples of ACEI therapy• Occurrence of ARF should prompt a search for:Occurrence of ARF should prompt a search for:

– Hypotension (MAP <65 mmHg), volume depletion, or nephrotoxin Hypotension (MAP <65 mmHg), volume depletion, or nephrotoxin administrationadministration

• Correct or remove these factorsCorrect or remove these factors• Consider bilateral renal artery stenosisConsider bilateral renal artery stenosis

• ACEIs should be discontinued temporarily while precipitating ACEIs should be discontinued temporarily while precipitating factors for ARF are correctedfactors for ARF are corrected

– ARBs are ARBs are notnot an appropriate substitute under these conditions!!! an appropriate substitute under these conditions!!!– ACEI therapy can be reinstituted once these factors are correctedACEI therapy can be reinstituted once these factors are corrected

• Hyperkalemia is a potential complication, particularly in patients with Hyperkalemia is a potential complication, particularly in patients with DM or CRFDM or CRF

– Monitor K+ early after initiation of therapy, reduce dietary K+, avoid agents Monitor K+ early after initiation of therapy, reduce dietary K+, avoid agents that aggravate hyperkalemia that aggravate hyperkalemia


• Start with a low doseStart with a low dose

• Increase dose if well tolerated (hold parameters for Increase dose if well tolerated (hold parameters for BP and HR)BP and HR)

• Dose NOT determined by symptoms, titrate to target Dose NOT determined by symptoms, titrate to target dosedose

• Monitor renal function & serum KMonitor renal function & serum K++ • Avoid initiating while volume depletedAvoid initiating while volume depleted

Diuretics, ACE InhibitorsDiuretics, ACE Inhibitors

Reduce the number of sacks on the wagonReduce the number of sacks on the wagon

ARBsARBs

• RecommendationsRecommendations– ARBs approved for the treatment of HFARBs approved for the treatment of HF are recommended are recommended

in patients with current or prior symptoms of HF and in patients with current or prior symptoms of HF and reduced LVEF who are ACEI intolerantreduced LVEF who are ACEI intolerant (Class I; LOE A)(Class I; LOE A)

– ARBs are reasonable to use as ARBs are reasonable to use as alternatives to ACEIsalternatives to ACEIs as 1 as 1stst line therapy for patients with mild to moderate H F and line therapy for patients with mild to moderate H F and reduced LVEF, especially for patients reduced LVEF, especially for patients alreadyalready taking ARBs taking ARBs for other indications for other indications (Class IIa; LOE A)(Class IIa; LOE A)

– The The addition of an ARBaddition of an ARB may be considered in persistently may be considered in persistently symptomatic patients with reduced LVEF who have already symptomatic patients with reduced LVEF who have already been treated with conventional therapy been treated with conventional therapy (Class IIb; LOE B)(Class IIb; LOE B)



ARBsARBs

ARBARB Initial DoseInitial Dose Maximum DoseMaximum Dose

CandesartanCandesartan 4-8 mg daily4-8 mg daily 32 mg daily32 mg dailyLosartanLosartan

Not FDA approvedNot FDA approved

25-50 mg day25-50 mg day 50-100 mg day50-100 mg day

ValsartanValsartan 20-40 mg bid20-40 mg bid 160 mg bid160 mg bid



Beta-blockersBeta-blockers

• RecommendationsRecommendations– Beta-blockers Beta-blockers and ACEIsand ACEIs should be used in should be used in all all patients with patients with

recent or remote history of MI recent or remote history of MI regardless of EFregardless of EF or presence or presence of HF of HF (Class I: LOE A)(Class I: LOE A)

– Beta-blockers are indicated in Beta-blockers are indicated in allall patients patients withoutwithout a history a history of MI who have of MI who have reduced LVEF with no HF reduced LVEF with no HF symptomssymptoms(Class I: LOE C)(Class I: LOE C)




Beta-BlockersBeta-Blockers

• Cardioprotective effects due to blockade of excessive SNS Cardioprotective effects due to blockade of excessive SNS stimulation stimulation

• In the short-term, beta blocker decreases myocardial In the short-term, beta blocker decreases myocardial contractility; increase in EF after 1-3 months of usecontractility; increase in EF after 1-3 months of use

• Long-term, placebo-controlled trials have shown symptomatic Long-term, placebo-controlled trials have shown symptomatic improvement in patients treated with certain beta-blockersimprovement in patients treated with certain beta-blockers11

• When combined with conventional HF therapy, beta-blockers When combined with conventional HF therapy, beta-blockers reduce the combined risk of morbidity and mortality, or reduce the combined risk of morbidity and mortality, or disease progressiondisease progression11

1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management 1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 p. 20.of Chronic Heart Failure in the Adult, 2001 p. 20.


• Mechanism of action:Mechanism of action: Density of ßDensity of ß1 1 receptors receptors NeurohormonalNeurohormonal activationactivation

• Slow/reverse ventricular remodeling Slow/reverse ventricular remodeling • Decreased myocyte death from catecholamine- induced necrosis or Decreased myocyte death from catecholamine- induced necrosis or

apoptosisapoptosis HRHR

• Symptomatic worsening of HF Symptomatic worsening of HF • Low doses, slow upward titrationLow doses, slow upward titration

• AntiischemicAntiischemic

• AntihypertensiveAntihypertensive• AntiarrhythmicAntiarrhythmic• Antioxidant, AntiproliferatievAntioxidant, Antiproliferatiev


• Increase EFIncrease EF• Decrease ventricular massDecrease ventricular mass

• Reduce systolic and diastolic volumesReduce systolic and diastolic volumes• Decrease hospitalization and mortalityDecrease hospitalization and mortality

– Greater benefit seen at higher dosesGreater benefit seen at higher doses

Patients receiving diuretics, ACE inhibitors, ± digoxin; follow-up 6 months; placebo (n=84), carvedilol (n=261).*Results from the Multicenter Oral Carvedilol Heart Failure Assessment (MOCHA) trial (n=345).†P.005 vs placebo.‡P.0001 vs placebo.Adapted from Bristow MR et al. Circulation. 1996;94:2807–2816.

Carvedilol

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Even low doses of B-blockade can have a Even low doses of B-blockade can have a dramatic effectdramatic effect

COPERNICUSCIBIS II MERIT-HF

NYHA Class III-IV (N=2647) II - IV (N=3391) IV (N=2289) Entry criteria LVEF 35% LVEF 40% LVEF 25%Treatment Bisoprolol Metoprolol CR/XL CarvedilolResults 34% 34% 35% (% reduction in death)

Time (years)

Effects of Beta-Blockers on MortalityEffects of Beta-Blockers on Mortality

1. CIBIS II Investigators and Committees. Lancet. 1999;353:9-13. 2. MERIT-HF Study Group. Lancet. 1999;353:2001-2007. 3. Packer M et al. N Engl J Med. 2001;344:1651-1658.

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-blocker

Placebo

-blocker

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-blocker

Placebo

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Beta-blockersBeta-blockers• RecommendationsRecommendations

– Beta-blockers Beta-blockers and ACEIsand ACEIs should be used in should be used in all all patients with recent or remote history of MI patients with recent or remote history of MI regardless of EFregardless of EF or presence of HF or presence of HF (Class I: (Class I: LOE A)LOE A)

– Beta-blockers are indicated in Beta-blockers are indicated in allall patients patients withoutwithout a history of MI who have a history of MI who have reduced reduced LVEF with no HF symptomsLVEF with no HF symptoms(Class I: LOE C)(Class I: LOE C)



Beta-blockersBeta-blockersMedicationMedication Mechanism Mechanism

of actionof actionNYHA NYHA ClassClass

Initial doseInitial dose Target DoseTarget Dose

Bisoprolol Bisoprolol (Zebeta®)(Zebeta®)

not FDA-approvednot FDA-approved

1-selective1-selective III-IVIII-IV 1.25 mg/day1.25 mg/day 10 mg/day10 mg/day

Carvedilol Carvedilol (Coreg®)(Coreg®)

Coreg CRCoreg CR

Non-selective Non-selective -blocker, -blocker, 1-blocker1-blocker

II-IVII-IV 3.125 mg bid3.125 mg bid

10 mg/day10 mg/day

25 mg bid (< 85 kg)25 mg bid (< 85 kg)

50 mg bid (> 85 kg)50 mg bid (> 85 kg)

80 mg/day80 mg/dayMetoprolol Metoprolol succinate succinate (Toprol (Toprol XL®)XL®)

1-selective1-selective II-IIIII-III 12.5-25 mg 12.5-25 mg dayday

200 mg/day200 mg/day

ß-Blockersß-Blockers

Limit the donkey’s speed, thus saving energyLimit the donkey’s speed, thus saving energy


Contraindications: Contraindications: – Cardiogenic shock, symptomatic hypotensionCardiogenic shock, symptomatic hypotension

– HypersensitivityHypersensitivity

– Bradycardia HR<45Bradycardia HR<45

– 22ndnd and 3 and 3rdrd degree heart block; (P-R interval greater degree heart block; (P-R interval greater than or equal to 0.24 sec) than or equal to 0.24 sec) –– unless pacemaker places unless pacemaker places


Warnings/Precautions:Warnings/Precautions:– Anesthesia/surgery (myocardial depression) Anesthesia/surgery (myocardial depression)

– Bronchospastic disease (less with cardioselective agents)Bronchospastic disease (less with cardioselective agents)

– Decompensated HFDecompensated HF– May mask s/sx hypoglycemiaMay mask s/sx hypoglycemia

– May mask signs of hyperthyroidism/thyrotoxicosis May mask signs of hyperthyroidism/thyrotoxicosis

– PVD PVD –– use with caution since may aggravate arterial insufficiency use with caution since may aggravate arterial insufficiency

– Avoid abrupt withdrawal (may result in hypertension, tachycardia, Avoid abrupt withdrawal (may result in hypertension, tachycardia, ischemia, angina, MI, and sudden death) ischemia, angina, MI, and sudden death) –– discontinue over 1-2 discontinue over 1-2 weeksweeks


Aldosterone AntagonistsAldosterone Antagonists

• Generally well-toleratedGenerally well-tolerated

• Shown to reduce heart failure-related morbidity and Shown to reduce heart failure-related morbidity and mortality mortality

• Generally reserved for patients with NYHA Class III-IV HFGenerally reserved for patients with NYHA Class III-IV HF

• Side effects include hyperkalemia and gynecomastia. Side effects include hyperkalemia and gynecomastia. Potassium and creatinine levels should be closely Potassium and creatinine levels should be closely monitoredmonitored


• Randomized Aldactone Evaluation Study Randomized Aldactone Evaluation Study (RALES)(RALES)– 30% relative risk reduction in all-cause mortality and 35% 30% relative risk reduction in all-cause mortality and 35%

reduction in hospitalizations reduction in hospitalizations

• The Eplerenone Post-Acute Myocardial Infarction Heart The Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Failure Efficacy and Survival (EPHESUS)(EPHESUS) Trial Trial– 15% relative risk reduction in all-cause mortality and 15% relative risk reduction in all-cause mortality and

hospitalizations for HFhospitalizations for HF

N Engl J Med. 1999;341(10):709-17.N Engl J Med. 2003;348(14):1309-21.

Study Design NYHA Class III-IV (N= 1663)

EF 35% Frequent monitoring of

potassium Result: 30% reduction in death

Effect of Spironolactone on SurvivalEffect of Spironolactone on Survival(Aldosterone blockade)(Aldosterone blockade)

Pitt B et al. N Engl J Med. 1999;341:709-717.

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0.90

0.80

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Spironolactone

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Effect of Eplerenone on Sudden Cardiac Death

Pitt,NEJM 2003,348,p.1309


• RecommendationsRecommendations– Addition of an aldosterone antagonist is reasonable in Addition of an aldosterone antagonist is reasonable in

selected patients with moderately severe to severe selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal monitored for preserved renal function and normal potassium concentration. potassium concentration.

• Creatinine should be Creatinine should be 2.5 mg/dL in men or 2.5 mg/dL in men or 2.0 mg/dL in 2.0 mg/dL in women and potassium should be women and potassium should be 5.0 mEq/L 5.0 mEq/L (Class I; LOE B)(Class I; LOE B)




ARBARB Initial DoseInitial Dose Maximum DoseMaximum Dose

SpironolactoneSpironolactone 12.5-25 mg daily12.5-25 mg daily 25 mg daily or bid25 mg daily or bidEplerenoneEplerenone 25 mg daily25 mg daily 50 mg daily50 mg daily



VasodilatorsVasodilators

• Hydralazine + NitratesHydralazine + Nitrates– NitratesNitrates

• Activate guanylate cyclase to Activate guanylate cyclase to cGMP in vascular smooth cGMP in vascular smooth muscle muscle venodilation venodilation preload preload

• Inhibit ventricular remodeling processInhibit ventricular remodeling process

– HydralazineHydralazine• Direct-acting vasodilator on predominantly arterial smooth Direct-acting vasodilator on predominantly arterial smooth

muscle muscle SVR (afterload) SVR (afterload) • Prevent nitrate tolerance, antioxidant effectsPrevent nitrate tolerance, antioxidant effects

Vasodilators: Clinical DataVasodilators: Clinical Data

• Veteran Affairs Cooperative Studies Veteran Affairs Cooperative Studies • V-HeFT-IV-HeFT-I

– Hydralazine 75 mg po qid + ISDN 40 mg qid vs prazosin 5 Hydralazine 75 mg po qid + ISDN 40 mg qid vs prazosin 5 mg qd in addition to std therapymg qd in addition to std therapy

• Hydralzine + nitrates Hydralzine + nitrates mortality by 38% , 25%, and 23% at mortality by 38% , 25%, and 23% at 1, 2, and 3 years1, 2, and 3 years

• V-HeFT-IIV-HeFT-II– Hydralazine 75 mg po qid + ISDN 40 mg qid vs. enalapril Hydralazine 75 mg po qid + ISDN 40 mg qid vs. enalapril

and enalapril was superiorand enalapril was superior


• A-HeFTA-HeFT– Randomized, placebo-controlled, double-blind clinical trialRandomized, placebo-controlled, double-blind clinical trial22

– 1,050 pts, self-identified as black1,050 pts, self-identified as black22 with stable symptomatic HF with stable symptomatic HF

– LVEF LVEF <<35% or left ventricular internal diastolic dimension >2.9 35% or left ventricular internal diastolic dimension >2.9 cm/mcm/m22 plus LVEF <45% plus LVEF <45%22

• 1% NYHA class II, 95% NYHA class III , 4% NYHA class IV 1% NYHA class II, 95% NYHA class III , 4% NYHA class IV • Mean age upon entry: 57Mean age upon entry: 5711

• 60% men, 40% women 60% men, 40% women

– Patients randomized to receive either their current standard Patients randomized to receive either their current standard therapies + BiDil (n=518) or their current standard therapies + therapies + BiDil (n=518) or their current standard therapies + placeboplacebo11 (n=532) (n=532)

– BiDil® tablet = Hydralazine 37.5 mg/ISDN 20 mgBiDil® tablet = Hydralazine 37.5 mg/ISDN 20 mg

• 2 tablets po tid2 tablets po tid


• A-HeFT ResultsA-HeFT Results– Additional 43% reduction in mortality beyond current standard Additional 43% reduction in mortality beyond current standard

therapies (therapies (PP=0.012)=0.012)11 – Additional 39% risk reduction in first hospitalization for heart Additional 39% risk reduction in first hospitalization for heart

failure beyond current standard therapies (failure beyond current standard therapies (PP<0.001)<0.001)– Significant additional improvement in symptoms of heart failureSignificant additional improvement in symptoms of heart failure11

VasodilatorsVasodilators

• RecommendationsRecommendations– The addition of a combination of hydralazine and a nitrate is The addition of a combination of hydralazine and a nitrate is

reasonable for patients with reduced LVEF who are reasonable for patients with reduced LVEF who are already already taking an ACEItaking an ACEI and beta-blocker for symptomatic HF and who and beta-blocker for symptomatic HF and who have persistent symptoms have persistent symptoms (Class IIa; LOE A)(Class IIa; LOE A)

– A combination of hydralazine and a nitrate might be reasonable in A combination of hydralazine and a nitrate might be reasonable in patients with current or prior symptoms of HF and reduced LVEF patients with current or prior symptoms of HF and reduced LVEF who are who are who cannot be given a ACEI or ARB because of drug who cannot be given a ACEI or ARB because of drug intolerance, hypotension, or renal insufficiency intolerance, hypotension, or renal insufficiency (Class IIb; LOE (Class IIb; LOE C)C)



Vasodilators: PrecautionsVasodilators: Precautions

• HydralazineHydralazine– Systemic lupus erythematosus Systemic lupus erythematosus

– HypotensionHypotension– TachycardiaTachycardia– Peripheral neuritis, evidenced Peripheral neuritis, evidenced

by paresthesia, numbness, and by paresthesia, numbness, and tingling, which may be related tingling, which may be related to an antipyridoxine effect.to an antipyridoxine effect.

• Pyridoxine should be added to Pyridoxine should be added to therapy if such symptoms therapy if such symptoms develop. develop.

• NitratesNitrates– HypotensionHypotension

– HeadachesHeadaches

– Tolerance – separate Tolerance – separate dosing by 10-12 hoursdosing by 10-12 hours

• Example: Dose at 9am, Example: Dose at 9am, 3pm, 9 pm3pm, 9 pm

– Drug interactions with Drug interactions with Viagra®- like drugsViagra®- like drugs

Treatment Approach for the Patient Treatment Approach for the Patient with Heart Failurewith Heart Failure

Stage AStage A

At high risk, no At high risk, no structural diseasestructural disease

Stage BStage B

Structural heart Structural heart disease, disease,

asymptomaticasymptomatic

Stage DStage D

Refractory HF Refractory HF requiring requiring

specialized specialized interventionsinterventions

TherapyTherapy

• Treat HypertensionTreat Hypertension

• Treat lipid Treat lipid disordersdisorders

• Encourage regular Encourage regular exerciseexercise

• Discourage alcohol Discourage alcohol intakeintake

• ACE inhibitionACE inhibition

TherapyTherapy

• All measures All measures under stage Aunder stage A

• ACE inhibitors in ACE inhibitors in appropriate appropriate patientspatients

• Beta-blockers in Beta-blockers in appropriate appropriate patientspatients

TherapyTherapy

• All measures All measures under stage Aunder stage A

Drugs:Drugs:

• DiureticsDiuretics

• ACE inhibitorsACE inhibitors

• Beta-blockersBeta-blockers

• DigitalisDigitalis

• Dietary salt Dietary salt restrictionrestriction

TherapyTherapy

• All measures All measures under stages A,B, under stages A,B, and Cand C

• Mechanical assist Mechanical assist devicesdevices

• Heart Heart transplantationtransplantation

• Continuous (not Continuous (not intermittent) IV intermittent) IV inotropic infusions inotropic infusions for palliationfor palliation

• Hospice careHospice care

Stage CStage C

Structural heart Structural heart disease with disease with prior/current prior/current

symptoms of HFsymptoms of HF

Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2005Chronic Heart Failure in the Adult, 2005

Current Treatment OptionsCurrent Treatment Options

Cardiac Resynchronization Therapy (CRT)

• Symptomatic heart failure despite OPT

• Wide QRS complex

• LV dysfunction EF < 35%

• NYHA Class III/IV

Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

Increase the donkeyIncrease the donkey’s’s (heart) efficiency (heart) efficiency

Reverse Remodeling in HFReverse Remodeling in HF

10/10/03 8/13/07

Implanted Cardioverter Defibrillator (ICD)Implanted Cardioverter Defibrillator (ICD)

ICD prevents SCDICD prevents SCD

CRT improves Quality of CRT improves Quality of Life and NYHALife and NYHA

Heart Failure patients Heart Failure patients should be managed on should be managed on optimal background therapyoptimal background therapy

Assist Devices: Bridge to TransplantAssist Devices: Bridge to Transplant

Other New ModalitiesOther New Modalities – Research Stage – Research Stage• Cell and Gene TherapyCell and Gene Therapy

* Utility in treating acute myocardial infarction* Utility in treating acute myocardial infarction -we cannot limit infarct size -we cannot limit infarct size

-we can rebuild infarcted muscle-we can rebuild infarcted muscle• Potential Cells to use:Potential Cells to use:

* cardiac myocytes* cardiac myocytes * skeletal muscle cells* skeletal muscle cells * endothelial cells* endothelial cells * progenitor cells* progenitor cells

* pluripotent cells* pluripotent cells

“Knowing is not enough; we must apply.Willing is not enough; we must do.”

- Goethe

heart failure: evaluation and treatment anecita fadol, phd, rn,fnp-bc nurse practitioner

Documents

heart muscle

heart failurecardiomyopathy

heart failure diagnosisdiscuss

management of heart

congestive heart failure

cmphfischemic heart

american heart association

demartinis et