Chronic Management of Heart FailureTopic Discussion

Outline

•Epidemiology•Etiology•Pathophysiology•Presentation

▫Classification•Treatment of chronic heart failure

▫Monitoring

What is Heart Failure

•Heart can’t pump enough blood to meet the metabolic needs of the body▫Clinically = loss of energy

•Systolic▫Reduced left ventricular ejection fraction

(LVEF)•Diastolic

▫Disturbed relaxation

Epidemiology

•Five million Americans •550,000 new cases/year•Most common hospital discharge

diagnosis in adults over 65•Overall 5 year survival after diagnosis -

50%

Etiology

•Reduction in muscle mass▫Myocardial infarction (MI)▫Coronary Artery Disease

•Dilated cardiomyopathies •Ventricular hypertrophy

▫Pressure overload Hypertension

▫Volume overload

Pathophysiology

•Decreased cardiac output•Compensatory mechanisms

▫Tachycardia and increased contractility ▫Increase preload (sodium (Na) and H2O

retention)▫Vasoconstriction

•Ventricular hypertrophy and remodeling

Pathophysiology

•Neurohormonal model▫Angiotensin II

Aldosterone ▫Norepinephrine/catecholamines▫Endothelin▫Inflammatory cytokines

Pathophysiology

•Decreased left ventricular ejection fraction (LVEF)

•Increased preload ▫With minimal changes in stroke volume

•Increased afterload▫Slight change in afterload causes

significant changes in stroke volume

Presentation• Fatigue• Pulmonary congestion–Dyspnea, orthopnea, paroxysmal nocturnal

dyspnea, cough– Pulmonary edema, pleural effusion– Rales, S3

• Systemic congestion– Jugular Venous Distention (JVD)– Peripheral edema/weight gain, cool extremities–Nausea/vomiting–Hepatojugular reflux, splenomegaly,

hepatomegaly

Presentation

•New York Heart Association Classification▫Stage 1

No limitations of activity▫Stage 2

Slight, mild limitation of activity▫Stage 3

Marked limitation of physical activity▫Stage 4

Severe limitation of physical activities; symptoms at rest

Presentation

•ACC/AHA staging▫Stage A

Patients at high risk ▫Stage B

Patients with structural heart disease but no heart failure (HF) signs or symptoms

▫Stage C Patients with structural disease and symptoms

▫Stage D Refractory HF

Treatment of Chronic Heart Failure

Treatment

•Goals▫Short-term

Relieve symptoms and improve quality of life▫Long-term

Slow progression of the disease and prolong survival

▫Pharmacotherapeutic Disrupt neurohormonal mechanisms Decrease preload Decrease afterload

Treatment

•Non-drug ▫Treat the underlying cause▫Restrict sodium (Na)<2g/day▫Avoid overexertion▫Avoid alcohol▫Immunizations▫Avoid drugs that worsen heart failure

Treatment: Drug Therapy• Drugs that improve survival– Angiotension converting enzyme inhibitor (ACE-

I)– Beta blockers– Aldosterone antagonists

• Drugs that improve symptoms– Diuretics– Digoxin

• Alternatives– Angiotension receptor blocker (ARB)–Hydralazine/Isosorbide dinitrate (ISDN)

Treatment: General ApproachStage Treatment Alternative

s

A Risk factor reduction

B (MI or LVEF<40%) ACE-I + Beta Blocker

ARB

C Fluid retention

Frequent hospitalizationsSevere + low LVEF or

early after MI

ACE-I + Beta Blocker+ Diuretic+ Digoxin+ Aldosterone antagonist

ARB, hydralazine/ISDN

Treatment: ACE-I• Patients: stage A with other indications, stages B,C,D• Benefit: alleviate symptoms, reduce risk of death and

hospitalization• MoA: prevents conversion of angiotensin I to

angiotensin II– Reduce preload and afterload, interrupt neurohormonal

cycle• Dosing– Start low and titrate to target

Drug Initial Dose Target Dose

Captopril 6.25mg TID 50 TID

Enalapril 2.5mg BID 10-20 BID

Lisinopril 5mg QD 20-40 QD

Ramipril 1.25-2.5mg QD 10 mg QD

Trandolapril 0.5mg QD 4 mg QD

Treatment: ACE-I • Adverse events

▫ Hypotension Don’t use if systolic blood pressure (SBP) <80mmHg

▫ Angioedema▫ Acute renal failure

Risk increases: hypovolemic, high dose diuretics, renal artery stenosis

▫ Cough▫ Hyperkalemia▫ Others: dysgeusia, rash

• Monitoring▫ Potassium (K+), serum creatinine (Scr), after 1-2

weeks▫ Blood pressure (BP)

Treatment: ARBs•Alternative when patient is ACE-I intolerant•Benefit: non inferior to ACE-I•MoA: block angiotensin receptor•Dosing

Drug Initial Dose Target Dose

Candesartan 4-8mg QD 32mg QD

Valsartan 20-40mg BID 160mg BID

Losartan 25-50mg QD 50-100mg QD

Treatment: ARBs

•Adverse events▫Hypotension

Don’t use if SBP <80mmHg▫Angioedema▫Acute renal failure▫Hyperkalemia

•Monitoring▫K+, Scr, after 1-2 weeks▫BP

Treatment: Beta Blockers• Patients: stages B, C, D• Benefit: reduce risk of death and hospitalization,

improve symptoms• Effects: inhibit effects of the sympathetic

nervous systems• Agents and dosing– Start when patient is stable– Start low and go slow – 2 week intervals– Expect transient discomfort: congestion,

hypotensionDrug Initial Dose Target Dose

Bisoprolol 1.25 mg QD 10mg QD

Carvedilol 3.125mg BID 25mg BID

Carvedilol CR 10mg QD 80mg QD

Metoprolol succinate

12.5-25mg QD 200mg QD

Treatment: Beta Blockers• Monitoring– BP– HR– Weight daily and adjust

diuretic dose• Adverse events– Fluid retention– Hypotension/bradycardia– Fatigue– Depression– Erectile dysfunction

• Disease state considerations▫ Asthma/COPD▫ Diabetes▫ Peripheral Vascular

Disease/Raynauds• Don’t stop abruptly

Treatment: Aldosterone Antagonists• Patients: severe heart failure and low LVEF, or

early after MI• MoA: compete with aldosterone• Benefit: reduced risk of death and

hospitalization, symptom improvement▫ Select patients carefully

SCr <2.5mg/dl or <2.0mg/dl Don’t use in CrCl<30ml/min

K+ < 5.0meq/L• Dosing

Drug Initial Dose Target Dose

Spironolactone 12.5-25mg QD 50mg QD

Eplerenone 25mg QD 50mg QD

Treatment: Aldosterone Antagonists• Monitoring– BP– SCr• Renally adjusted

– K+ at 3 days, 1 week, monthly x 3 months– Start series over if changes made to dose or

changes to ACE-I/ARB regimen–Decrease dose or discontinue when k+ >5.5meq/l

• Adverse events–Hyperkalemia – Gynecomastia • Less with eplerenone

Treatment: Loop Diuretics•Patients: with fluid overload•Benefit: rapid symptom relief•MoA: inhibit Na reabsorption in distal tubule•Effects: diuresis and dilation of veins (IV)•Dosing

▫Use higher doses in renal insufficiency▫Oral loop equivalents

1mg bumetanide=20mg torsemide=40mg furosemide

Treatment: Loop Diuretics• Monitoring

▫Weight Goal weight loss is 0.5-1kg/day

▫Signs and symptoms of fluid overload▫BP▫Electrolytes

• Adverse events▫Electrolyte (K+, Mg2+, Ca2+) and fluid

depletion▫Hypotenstion ▫Azotemia ▫Rash▫Ototoxicity

Weight Gain

•When to call a doctor▫2-3 pounds in a day▫5 pounds in 5 days

Treatment: Digoxin• Patients: frequent hospitalizations, rate

control in atrial fibrillation • Benefit: reduce symptoms, prevent

hospitalization, control rhythm, enhance exercise tolerance

• MoA: inhibit Na/K ATPase which results in increased contractility

• Dosing▫0.125-0.250mg QD▫Plasma concentration

▫ 0.5-1.0ng/mL

Treatment: Digoxin•Monitoring

▫HR and rhythm▫Levels at 5-7 days; 6-12 hours after dose▫Electrolytes and renal function

•Adverse events▫Cardiac arrhythmias

PAT with block▫GI upset▫Neurological complaints▫Vision changes

Treatment: Digoxin

• Drug interactions ▫ Verapamil, quinidine, amiodarone

• Digoxin toxicity▫ Predisposing factors: hypokalemia,

hypomagnesemia, hypothyroid, hypercalcemia

▫ Treatment Digoxin immune fab

Treatment: ISDN/Hydralazine•Alternative for ACE-I/ARB

▫African American•MoA: arterial and venous dilation•Dosing

▫Nitrate-free interval

Drug Initial Dose Target Dose

Hyralazine 10-25mg T-QID

225-300mg/day divided

ISDN 20mg T-QID 160mg/day divided QID

Bidil ® ISDN 20mg + hydrlazine 37.5 mg

1 tablet TID 2 tablets TID

Treatment: ISDN/Hydralazine

•Monitoring▫BP/HR▫ANA titer

•Adverse events▫Headache▫GI upset▫Dizziness▫Weakness

•Hard to tolerate/high pill burden

Treatment: Stage D

•Fluid overload: ▫2 Drug combination (i.e., loop +

metolazone) ▫Fluid restriction 2L/day

•Neurohormonal▫ACE-I’s and beta blockers

Less likely to tolerate•Other

▫Cardiac transplant, left ventricular assist device (LVAD)

Drugs that Worsen Heart Failure• Negative inotropes– Calcium channel blockers– Beta blockers– Antiarrhythmics:

disopyramide, flecainide, propafenone, sotalol

• Exogenous Na– Sodium polystyrene

sulfonate– Antibiotics– Antacids– Cough syrups

• Na-retaining products– NSAIDs– Glucocorticoids– Androgens/estrogens

• Cardiotoxics– Ethanol– Doxorubicin– Trastuzumab– Infliximab

• Others– Glitazones

Drugs that are Safe in Heart Failure•Calcium channel blockers

▫Amlodipine ▫Felodipine

•Antiarrhythmics▫Amiodarone▫Dofetilide

Treatment: Heart Failure with Normal LVEF•Control underlying disease states

▫BP▫Ventricular rate with A.fib

•Symptom control▫Diuretics for congestion▫Beta blockers, ACE-Is, ARBs, calcium

channel blockers might provide some symptom relief

Case

•50 yom presents with a new diagnosis of heart failure

•He takes hydrochlorothiazide 25mg daily for hypertension and uses ibuprofen ~3x/week for headaches.

•His LVEF is 50%•He is currently experiencing peripheral

edema and significant shortness of breath

Case•What stage of heart failure does the

patient have?▫Stage C

•What should we do with this patient’s medications today?▫ACE-I▫Loop diuretic (d/c hydrochlorothiazide)▫Stop ibuprofen

•What dose should we start at?▫Start low

Case

•What should we monitor?▫Weight, symptoms ▫K+, SCr▫BP

•What is the goal weight loss for this patient?▫0.5-1kg/day

•What else do we want to tell the patient?▫Non-drug therapy

Case• The patient returns in a few months and is

stable on lisinopril 30mg daily and furosemide 20mg daily.

• What do you want to do now?▫Add a beta blocker

• Which one?▫Metoprolol XL, bisoprolol, or carvedilol

• What dose?▫Start low and titrate!

• What do you want to tell the patient about his symptoms?▫They might get worse initially

Case

•What might you consider if the patient’s LVEF was low?▫Spironolactone

•What might you consider if the patient is having frequent hospitalizations?▫Digoxin