Heart Failure

Trennette R. Gilbert

University of Southern Nevada

College of Pharmacy

Definition Inability of the heart to circulate blood effectively enough

to meet the body’s needs May result from any abnormality of cardiac structure or function

A state of increased SNS (sympathetic nervous system) and RAAS (renin-angiotensin-aldosterone system) activation that promotes further cardiac deterioration

Forms of heart failure (HF) Chronic vs. acute Diastolic vs. systolic

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Epidemiology

Approximately 5 million Americans have HF Approximately 500,000 newly diagnosed each year

Men > women (until age 65) Affects nearly 10% of individuals ≥ 75 years old

#1 cause of hospitalization among Medicare patients

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Classification of HFACC/AHA Staging

Stage A At high risk of developing HF

Stage B Structural heart disease -

symptoms

Stage C Structural heart disease +

symptoms

Stage D Refractory HF

NYHA Functional Class Class I

No limitations on ordinary physical activity

Class II Ordinary physical activity

causes fatigue, dyspnea, palpitation

Class III Less-than ordinary activity

leads to symptoms

Class IV Symptoms are present at rest

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Chronic vs. Acute

Chronic HF (months – years) An index event causes the heart to undergo adaptive

changes over a long period of time Acute HF (hours – days)

Rapid failure due to a precipitating event Heart does not have time to undergo compensatory

adaptations

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Systolic vs. Diastolic

Systolic dysfunction Ejection fraction (EF) < 40% Ventricular contraction impaired

Etiology 2/3 of cases due to CAD 1/3 due to HTN, hyperthyroidism, cardiotoxins,

idiopathic Prevalence

Most common form

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Systolic vs. Diastolic cont…

Diastolic EF normal Ventricular relaxation/filling impaired

Etiology HTN, age-related decreases in elasticity,

cardiomyopathies Prevalence

Approximately 30% of cases

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Pathophysiology of HF An index event causes LV dysfunction

LV unable to fill with blood or generate enough force to expel blood forward → ↓ cardiac output

Body compensates by activating RAAS and SNS Results in tachycardia and fluid retention Neurohormones also have direct toxic effects Naturietic peptides (ANP, BNP), nitric oxide, and

bradykinin counter effects of RAAS and SNS In HF, these mechanisms become overwhelmed

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Presentation of Chronic HF

Dyspnea Fatigue Edema Exercise intolerance

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Drug Therapy for Chronic HF

Stage Medications

A ACEIs or ARBs in some patients

B ACEIs or ARBs in all patients + β-blocker in some patients

C ACEIs or ARBs + β-blocker in all patients +diuretics, digoxin, or aldosterone antagonists in some patients

D Same as C + chronic inotropes, end-of-life care

Goals of therapy Neurohormonal blockade Prevent/minimize fluid retention Manage symptoms Slow progression Decrease mortality

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Rationale for Medications Used in HFMedication Benefits

ACEIs ↓ morbidity & mortality↓ risk of developing HFPrevents post-MI remodeling

ARBs As or slightly less effective than ACEIs

β-blockers ↓ morbidity & mortality (nebivolol for elderly patients)Slow disease progression↑ ejection fraction

Digoxin ↓ hospitalizations

Diuretics Most effective at improving symptoms

Hydralazine/nitrates Alternative to ACEI or ARB↓ morbidity & mortality

Aldosterone antagonists ↓ morbidity & mortality in moderate – severe HF

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Etiology of Acute HF

Acute exacerbation of chronic HF Infection Acute MI Severe arrhythmia Noncompliance with medications

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Presentation of Acute HF

PCWP (mm Hg)

Warm & dry

Cold & dry

Warm & wet

Cold & wet

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Drug Therapy for Acute HF

Cold & dry Inotropes, vasodilators

Cold & wet Diuretics, inotropes, vasodilators

Warm & wet Diuretics, vasodilators

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Diuretics

IV loop diuretics (furosemide) recommended Most effective, even at low Crcl

Minimal response, consider: Fluid and sodium restriction Increase dose of loop diuretic or IV drip

Furosemide ceiling effect at 160 – 200 mg Continuous infusion 0.1 mg/kg/hr, double q 4-8h [maximum:

0.4 mg/kg/hr] Add a thiazide

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Vasodilators Consider in addition to diuretics if persistent fluid

overload w/o symptomatic hypotension Nesiritide

Recombinant BNP Has natriuretic effects and balances RAAS, SNS

Use in cold & wet or warm & wet patients Dosing: 2 mcg/kg bolus, 0.01 mcg/kg/min Requires no renal or hepatic elimination

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Inotropes Consider if hypoperfusion,end-organ damage, or

fluid overload refractory to diuretics and vasodilators Increase cardiac output

Dobutamine Positive inotropic, chronotropic effects Dosing: 2.5-5 μg/kg/min, titrate to max 20 μg/kg/min

Milrinone Positive inotropic effects Dosing: 50 μg/kg, then 0.375 μg/kg/min titrate to max 0.75

μg/kg/min

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Inotropes cont…

Levosimendan An investigational inotrope Increases contractility by increasing the sensitivity

of contractile proteins to intracellular calcium Also stimulates peripheral vasodilation Does not predispose to arrhythmias Not currently available in the US

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Prognosis of HF

At 5 years post-diagnosis: Less than 50% of patients will be alive

At 10 years post-diagnosis: Less than 25% will be alive

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Drugs to Avoid in HF NSAIDs

Associated with increased risk of exacerbations Thiazolidinediones

Cause fluid retention Metformin

Increased risk of lactic acidosis Antiarrhythmics

Ibutalide, sotalol have – inotropic effects Chemotherapeutic agents

Doxorubicin, trastuzumab, bevacizumab are toxic to heart

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Role of Pharmacists

Ensure heart failure patients are on appropriate medications Most should be on ACEI or ARB Know which medications should be avoided

Stress medication compliance Lack of compliance can lead to acute HF,

hospitalization and ↑ costs

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References

Kusumoto Fred M, "Chapter 10. Cardiovascular Disorders: Heart Disease" (Chapter). McPhee, SJ, Hammer, GD: Pathophysiology of Disease: An Introduction to Clinical Medicine, 6e: http://nv-ezproxy.usn.edu:2062/content.aspx?aID=5367630.

Parker Robert B, Rodgers Jo E, Cavallari Larisa H, "Chapter 16. Heart Failure" (Chapter). Joseph T. DiPiro, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey: Pharmacotherapy: A Pathophysiologic Approach, 7e: http://nv-ezproxy.usn.edu:2062/content.aspx?aID=3189842.

Mann Douglas L, "Chapter 227. Heart Failure and Cor Pulmonale" (Chapter). Dennis L. Kasper, Eugene Braunwald, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, Kurt J. Isselbacher: Harrison's Principles of Internal Medicine, 17e: http://nv-ezproxy.usn.edu:2062/content.aspx?aID=2902061.

Colucci, WS, Gottlied, SS, Yeon, SB. Evaluation and management of asymptomatic left ventricular systolic dysfunction. Up to date online. Feb 2009.

MS Nieminen. Pharmacological options for acute heart failure syndromes: current treatments and unmet needs. Eur Soc Cardiology. Vol 7, Suppl B. pp. B20-B24. 2005.

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