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Management of Heart Failure Topic Discussion Heart failure: heart can’t pump enough blood to meet the metabolic needs of the body Systolic: decreased left ventricular ejection fraction (LVEF) Diastolic: disturbed relaxation Pathophysiology 1. Injury a. Reduction in muslce mass (MI), dilated cardiomyopathies, ventricular hypertrophy (hypertension) 2. Decreased cardiac output a. Cardiac output = stroke volume (SV)* heart rate (HR) 3. Compensatory mechanisms a. Tachycardia and increased contractility b. Increase preload (Sodium (Na) and water (H2O) retention) i. Preload: the degree of stretch at the end of diastole; approximated by LVEF c. Vasoconstriction (increases afterload) i. Afterload: the force the heart must overcome to eject blood 4. Ventricular hypertorophy and remodeling a. Changes the shape, size, structure and function of the ventricle making it harder for the heart to work Neurohormonal model o Renin-angiotension-aldosterone system (RAAS) activation leads to vasoconstriction, catecholamine release, Na and H2O retention, remodeling o Catecholamines: increased heart rate, vasoconstriction, toxic to the myocardium o Endothelin: vasoconstriction o Inflammatory cytokines Presentation Symptoms and signs o Fatigue o Pulmonary congestion results in dyspnea, orthopnea, paroxysmal nocturnal dyspnea, cough, pulmonary edema, pleural effusion, rales, S3 o Systemic congestion results in JVD, peripheral edema, weight gain, cool extremities, nausea/vomiting, hepatogulular reflux, splenomegaly, hepatomegaly Staging (New York Heart Association Classification) o Stage 1: no limitations of activity o Stage 2: slight, mild limitation of activity o Stage 3: marked limitation of activity o Stage 4: severe limitation of activity; symptoms at rest Staging (ACC/AHA)1 o Stage A: patients at high risk of developing heart failure o Stage B: patients with structural heart disease but no signs and symptoms of heart failure o Stage C: patients with structural heart disase and symptoms o Stage D: refractory heart failure Treatment Goals o Short-term: relieve symptoms and improve quality of life o Long-term: slow progression of the disease and prolong survival o Pharmacotherapeutic: disrupt neurohormonal mechanisms, decrease preload, decrease afterload Non-drug o Treat the underlying cause o Restrict Na to <2g/day Management of Heart Failure Topic Discussion o Avoid overexertion o Avoid alcohol o Keep immunizations up to date o Avoid drugs that worsen heart failure Pharmacotherapy o Drugs that improve survival: ACE-I, beta blockers, aldosterone antagonists o Drugs that improve symptoms: diuretics, digoxin o Alternatives: Angiotension receptor blockers (ARBs), Isosorbide dinitrate ( ISDN)/hydralazine General approach to treatment (See Figure 1) Stage D treatment o Patients may need additional diuretics o Patients may be more sensitive to adverse events of Angiotension convertine enzyme inhibitor (ACE-I) and beta blockers o Consider surgical measures Heart Failure with Normal LVEF (diastolic dysfunction) Control underlying disease states (ie, bloodp pressure (BP), rate control with a. fib) Symptom control: diuretics for congestion, beta blockers, ACE-I, ARB, calcium channel blockers might provide some symptom relief Drugs that worsen heart failure Negative inotropes: calcium channel blockers, beta blockers, antiarrhythmics (disopyramide, flecanide, propafenone, sotalol) Exogenous Na: sodium polystyrene sulfonate, antibiotics, antacids, cough syrups Na-retaining: Nonsteroidal anti-inflammatory drugs (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, dofetolide References 1. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009;119:e391–479 Management of Heart Failure Topic Discussion 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 Questions What stage of heart failure does the patient have? What should we do with this patient’s medications today? What dose should we start at? What should we monitor? What is the goal weight loss for this patient? What else do we want to tell the patient? 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? Drugs and doses? What do you want to tell the patient about his symptoms? What might you consider if the patient’s LVEF was low? What might you consider if the patient is having frequent hospitalizations? Management of Heart Failure Topic Discussion Drug Class Appropriate Use Benefit Mechanism of Action Adverse Events Monitoring Patients in stage A with comorbid conditions requiring use. Patients in stages B, C, D Patients intolerant to ACE-I Symptom improvement, decreased hospitalization, decreased risk of death Symptom improvement and decreased mortality Prevent conversion of angiotensin I to angiogensin II Hypotension (don’t use if SBP <80mmHG), angioedema, acute renal failure, cough, hyperkalemia, dysgeusia, rash Hypotension (don’t use if SBP <80mmHG), angioedema, acute renal failure, hyperkalemia, K+ and SCr at 1-2weeks, BP K+ and SCr at 1-2weeks, BP Use caution if angioedema with ACE, renal failure and hyperkalemia are as likely to occur with ARB as ACE-I Patients in stages B, C, D Symptom improvement, decreased hospitalization, decreased risk of death Inhibits the sympathetic nervous system effects and protects against damage to myocardium Fluid retention (adjust diuretic), hypotension, bradycardia, fatigue, depression, erectile dysfunction BP, HR, weight daily Iniate when patient is stable, may cause worsening of symptoms initially Disease state considerations: airway disase, diabetes, PVD Don’t stop abruptly Severe HF with low LVEF Early after MI (Weigh risks) SCr <2.5mg/dl male or <2.0mg/dl female and k+ <5meq/l Patients with symptoms of fluid retention Symtpom improvement, decreased hospitalization, decreased risk of death Competes with aldosterone for binding to receptor Hyperkalemia (d/c or decrease dose when k+ >5.5), gynocomastia (change to eplerenone) BP, SCr K+ at 3 days, 1 week and monthly x 3 months (restart monitoring when dose change, or ACE-I or ARB started) Renally adjusted Rapid symptomatic improvement Inhibit reabsorption of Na in distal tubule Decreased electrolytes (k+, mg2+, ca2+), dehydration, hypotension, azotemia, rash, ototoxicity Weight (goal weight loss is 0.51kg/day), signs and symptoms of fluid overload, BP, electrolytes, SCr, BUN Digoxin Patients in stage C with frequent hospitalizations, rate control for a.fib Reduces symptoms, prevents hospitalization Inhibits Na/K ATPase resulting in increased contractility Arrhythmias, GI upset, neurological complaints, vision changes ISDN/Hydrala zine Alternative for ACEI/ARB, has better efficacy in African American patients Reduce mortality but not hospitilizations Arterial and venous dilation Headache, GI upset, dizziness, weakness HR and rhthm, levels (goal 0.51) at 5-7days and 6-12 hours after dose, electrolytes and renal function (renally eliminated) BP, HR, ANA titer Use higher doses in renal insufficiency, equivalents: 1mgB=20mgT=40mgF Ethacrynic acid does not have sulfa component Predisposing factors for toxicity: hypothyroid, hypomagnesemia, hypokalemia, hypercalcemia, most notable drug interactions: verapamil, quinidine, amiodarone Need nitrate free interval, hard to tolerate and high pill burden ACE-I ARB (candesartan, valsartan) Beta Blockers (carvedilol, bisoprolol, metoprolol succinate) Aldosterone antagonists Loop diuretics Blocks angiotensin receptor Notes Management of Heart Failure Topic Discussion Figure 11 Dosing1