Chronic Heart Failure Nicholas England and Dylan Hotham October 16, 2018 Background

Transcription

1 Background - Heart Failure (HF) is a common condition in the US that occurs when the heart is not able to supply sufficient O2-rich blood to the body - Due to the impaired ability of the ventricle to either fill or eject blood - Commonly classified as either ischemic or non-ischemic - Ischemic: Due to decreased blood supply (i.e., MI) - Non-Ischemic (i.e., long-standing uncontrolled HTN) - Pathophysiology - Terms - Cardiac Output (CO): The volume of blood that s pumped by the heart in 1 minute - A function of the HR and SV (the volume of blood ejected from the left ventricle (LV) during one complete heartbeat) - SV is dependent on preload, afterload, and contractility - CO = HR x SV - Cardiac Index (CI) relates the CO to the size of the patient, using the patient s BSA - CI = CO / BSA, or CI = (HR x SV) / BSA - Compensatory Mechanisms - Low CO moments neurohormones are released that increase blood volume, or increases the speed of the contractions - Might temporarily increase CO, but activation of neurohormones cause damage to the myocytes and produce changes in the size, shape, and composition of the heart (Cardiac Remodeling) - 3 main pathways activated in HF (Each pathway potentiates the others) - RAAS - Angiotensin II causes vasoconstriction of blood vessels, and stimulates the release of aldosterone & vasopressin - Aldosterone causes Na+ and H2O retention, and increases K+ excretion - Sympathetic Nervous System - Activation results in release of NE & Epi, which increases HR, contractility, and vasoconstriction - Vasopressin causes vasoconstriction and H2O retention Presentation and Diagnosis - Symptoms are primarily related to fluid overload - dyspnea, edema, cough, fatigue, weakness, exercise intolerance - Left Sided Signs and Symptoms: - Right Sided Signs and Symptoms: - Orthopnea - Peripheral edema - Paroxysmal nocturnal dyspnea - Ascites - Rales - Jugular venous distention - S3 gallop - Hepatojugular reflux - Hypoperfusion (renal impairment, cold extremities) - Hepatomegaly - Labs: BNP (>100 pg/ml) or NT-proBNP (>300 pg/ml) - Patients usually have periods of stability and exacerbation An echocardiogram provides information about the wall thickness and function, chamber size and pressure, valve size and function and the ejection fraction (EF). - EF measures how much blood is pumped out of the left ventricle during contraction 1

2 Classification of Heart Failure ACCF/AHA Stages of HF NYHA Functional Classification A At high risk for HF, but no structural heart disease of symptoms of HF none B Structural heart disease, but no signs or symptoms of HF I No limitation of physical activity. Ordinary physical activity does not cause HF symptoms C Structural heart disease with prior or current symptoms of HF I No limitation of physical activity. Ordinary physical activity does not cause HF symptoms II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in HF symptoms III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activities cause HF symptoms D Refractory HF requiring specialized interventions IV Unable to carry on any physical activity without HF symptoms, or symptoms occur at rest Lifestyle Management - Patients with HF should be instructed to do the following: Monitor & document body weight daily (in the AM after going to the bathroom) Maintain Na+ restriction of <1.5 grams/day in Stages A-B HF Smoking cessation Limit alcohol intake Avoid illicit drug use Consider weight reduction to <30 kg/m^2 to reduce the workload of the heart Notify provider when body weight increases by 2-4lbs in 1 day or 3-5lbs in 1 week, or when symptoms have worsen Maintain fluid restriction to L/day in Stage D HF (particularly for those with hyponatremia) Obtain Vaccines: Annual influenza vaccine, and Pneumococcal vaccines for those > 65 yoa or possess any patient-specific parameters Exercise training is recommended for those patients able to perform these activities Drugs that Worsen Heart Failure DPP-4 Inhibitors (alogliptin, sitagliptin) Antiarrhythmics - Avoid Class I agents (i.e., flecainide, quinidine, procainamide) - Amiodarone & dofetilide: Less risk of worsening HF Oncology Agents (i.e., doxorubicin, daunorubicin) Immunosuppressants (i.e., etanercept, rituximab, Interfurons) TZD s - Increases risk of edema All NSAID s (including celecoxib) Non-DHP CCB s (diltiazem, verapamil) Itraconazole 2

3 - Other medications that can cause or worsen HF: - Systemic steroids - Amphetamines, Stimulants, Illicit drugs - Triptans - Some Tyrosine Kinase Inhibitors (lapatinib, sunitinib) - Agents that cause fluid retention (i.e., trastuzumab, imatinib, docetaxel) - Excessive alcohol use Goals of Therapy: 1. Reduce Symptoms 2. Improve functional capacity 3. Decrease risk of hospitalizations 4. Delay disease progression 5. Prolong survival 6. Enhance quality of life Treatment Overview mortality for all patients: ACE inhibitors, ARBs, ARNI, Beta blockers, aldosterone receptor antagonist mortality for some patients: hydralazine and nitrates (Bidil) No effect on mortality: loop diuretics, digoxin, ivabradine (Corlanor) 3

4 Guideline Recommendations Medications Loop Diuretics (Nick): Used to decrease fluid volume to make it easier for the heart to pump. These agents block Na+ and Clreabsorption in the thick ascending limb of the loop of henle. An increased excretion of Na+, K+, Cl-, Mg2+, Ca2+, and H2O occurs Agents Dosing Warnings Other Notes Furosemide ( Lasix ) mg 1-2x/day - MAX: 600 mg/day Bumetanide ( Bumex ) mg 1-2x/day - MAX: 10 mg/day Torsemide ( Demadex ) mg/day - MAX: 200 mg/day Ethacrynic Acid ( Edecrin ) mg/day, or divided - MAX: 400 mg/day Sulfa allergy Not likely to cross-react - Store injection at room temp - Do not use solutions if not clear in color - Light-sensitive, solution comes in an amber bottle Light-sensitive, solution comes in an amber bottle *Listed Below* - Boxed Warning: Can lead to profound diuresis fluid & electrolyte depletion - Contraindication: Anuria - Side Effects: - Decreased K+/Na+/Mg2+/Cl-/Ca2+ - Increased HCO3/Metabolic Alkalosis - Hyperglycemia - Hyperuricemia - Increased TG s/tc - Photosensitivity - Orthostatic Hypotension - Ototoxicity (More-so with ethacrynic acid than other Loop Diuretics) - Monitoring: Renal function; BP, Electrolytes; I&O; Body weight; S/S of HF - Audiology testing with rapid IV administration or high doses 4

5 - Other Notes: Take early in day to avoid nocturia - Drug Interactions: - Avoid NSAID s in patients with HF Increase Na+ & H2O retention, leading to decreased Loop Diuretic effect, and potentially renal impairment - Combining Loop Diuretics with ACE Inhibitors/ARB s can lead to severe hypotension and worsening renal function - Combination Loop & Thiazide Diuretics can lead to pronounced electrolyte abnormalities - Can increase ototoxic effect of other ototoxic agents (i.e., Aminoglycosides) - Dose Conversions: - PO equivalent dosing: furosemide 40mg bumetanide 1mg torsemide 20mg ethacrynic acid 50mg - Furosemide IV:PO ratio = 1:2 (i.e., 20mg IV = 40mg PO) - IV:PO ratio for all other Loop Diuretics = 1:1 ACE-I and ARBs : RAAS activation preload and afterload; cardiac remodeling, improve LV function and morbidity and mortality. ACE Inhibitors Agents Target Dose in HF Contraindications Warnings Captopril ( Capoten ) Enalapril ( Vasotec ) Fosinopril 50 mg TID mg BID 40 mg daily -history of angioedema -use with aliskiren in patients with DM -use within 36 hours of Entresto -angioedema -hyperkalemia -hypotension -renal impairment -bilateral renal artery stenosis Lisinopril ( Prinivil, Zestril ) Quinapril (Accupril) Ramipril (Altace) mg daily 20 mg BID 10 mg daily Angiotensin Receptor Blockers Candesartan ( Atacand ) 32 mg daily Same as above (except no wash out period with Entresto) Losartan ( Cozaar ) mg daily *not indicated, but clinical trial shows benefit* Same as above except no cough and less incidence of angioedema Valsartan ( Diovan ) 160 mg BID - Recommended in all HF patients (NYHA Class I-IV) without contraindication, regardless of symptoms. - Side Effects: Cough, dizziness, headache, rash - Notes: - Titrate up to target dose, if possible. - Combination of ACE-I and ARB has been shown to decrease hospitalization - but not recommended due to increased side effects and risks Angiotensin Receptor and Neprilysin Inhibitor (ARNI): inhibits degradation of vasodilatory peptides that counteract RAAS activation and produces vasodilation. Agent Target Dose in HF Contraindications Warnings Sacubitril/Valsartan ( Entresto ) 50 mg = 24/26 mg sacubitril/valsartan 100 mg = 49/51 mg sacubitril/valsartan 200 mg = 97/103 mg sacubitril/valsartan Start: mg BID Target: 200 mg BID CrCl <30: 50 mg BID -use with ACE-I or ARBs -history of angioedema - use with aliskiren in DM patients -angioedema - renal impairment - hyperkalemia - hypotension -bilateral renal artery stenosis 5

6 - Indicated for NYHA class II-IV patients - reduces hospitalization, and cardiovascular death - Can be used first line monotherapy in place of ACE-I or ARB in select symptomatic NYHA class II-III patients who tolerate ACE-I or ARBs - Side Effects: cough, dizziness - Notes: Do not use with an ACE-I or another ARB - must have 36 hour wash-out period between stopping an ACE-I and starting Entresto Beta Blockers : Antagonize the effects of catecholamines at the beta-1 & beta-2 adrenergic receptors. These agents decrease vasoconstriction, improve cardiac function, and decrease morbidity & mortality. Beta-Blockers with intrinsic sympathomimetic activity should be avoided (i.e., acebutolol) Agents Dosing Contraindications Warnings Other Notes Beta-1 Selective Blockers Bisoprolol ( Zebeta ) Metoprolol succinate ( Toprol XL ) 1.25 mg/day, titrate q2wks as tolerated Target dose: 10 mg/day mg/day, titrate q2wks as tolerated Target dose: 200 mg/day *Listed Below* *Listed Below* Not FDA approved for HF, but benefit shown in clinical trials - Lopressor is not recommended for HF treatment per guidelines - IV is NOT equivalent to PO (Ratio = 2:5) - Can be cut at the score line - Preferably taken with food Non-Selective Beta & Alpha-1 Blocker Carvedilol ( Coreg, Coreg CR ) IR: 3.125mg BID - Target doses: 25mg BID if < 85kg; 50mg BID is >85kg Controlled Release: 10 mg/day, titrate q2wks as tolerated - Target dose: 80 mg/day Severe hepatic impairment Floppy Iris Syndrome has occurred in patients undergoing cataract surgery who were on an alpha-1 blocker Take with food to decrease rate of absorption and risk of orthostatic hypotension Dosing conversions are NOT 1:1 - Coreg 3.125mg BID = Coreg CR 10 mg/day - *Boxed Warning: Do NOT abruptly d/c (gradually taper over 1-2wks to avoid acute tachycardia, HTN, & ischemia) - *Contraindications: Severe bradycardia; 2nd/3rd degree heart block or SSS; cardiogenic shock - *Warnings: - Can mask hypoglycemic symptoms (except for sweating & hunger) - Can mask hyperthyroidism symptoms - Use caution in patients with Asthma/COPD - May aggravate psychiatric symptoms - *Side Effects: Decreased HR; Hypotension; Fatigue; Dizziness; Decreased libido; Depression; Increased TG s; Decreased HDL; Weight gain; Edema (esp. with carvedilol) - *Monitoring: HR, BP, S/S of HF - *Drug Interactions: - Can enhance hypoglycemic effects of Insulin & Sulfonylureas 6

7 - Can decrease insulin secretion, causing hyperglycemia - Use caution with other agents that decrease HR (i.e., digoxin, Non-DHP CCB s) - CYP2D6 Inhibitors can increase carvedilol levels - Rifampin can increase carvedilol levels - Carvedilol: P-gp Inhibitor can increase levels of P-gp substrates (i.e., digoxin, cyclosporine, dabigatran, ranolazine) Aldosterone Receptor Antagonists : These agents compete with aldosterone at receptor sites in the distal tubule and collecting ducts of the nephron. Agents Dosing Side Effects Other Notes Spironolactone ( Aldactone, CaroSpir ) mg/day Target dose: 25mg 1-2x/day CaroSpir : 20 mg/day if egfr >50 - Gynecomastia - Breast tenderness - Irregular menses - Amenorrhea - Impotence Carospir suspension is not therapeutically equivalent to Aldactone Non-Selective Aldosterone Receptor Antagonist (also blocks androgen) Eplerenone (Inspra) 25 mg/day, titrate based on K+ level Target dose: 50 mg/day Increased TG s Selective Aldosterone Receptor Antagonist (Does NOT exhibit endocrine SE s) - *Contraindications: Anuria; Hyperkalemia; CrCl <30 ml/min - Warnings: Do NOT initiate in HF patients with a K+ >5 meq/l, egfr <30, or SCr >2.0 mg/dl (females) or >2.5 mg/dl (males) - *Side Effects: Increased SCr, Hyperkalemia, Dizziness - *Monitoring: Electrolytes (Check K+ before initiating, and frequently thereafter); Renal function; BP; I&O; Body weight; S/S of HF - Drug Interactions: - Increases risk of hyperkalemia, monitor for additive effects if patient is taking other agents that can increase K+ - Additive antihypertensive effects when used with other agents that decrease BP - Use with NSAID s in patients with impaired renal function can cause severe hyperkalemia - Eplenerone: Major CYP3A4 substrate Use with strong CYP3A4 Inhibitors is C/I Hydralazine and Nitrates: Hydralazine afterload arterial vasodilation. Nitrates availability of nitric oxide vasodilation and preload Agents Dosing Side Effects Contraindications Warnings Hydralazine Start: mg TID-QID Target: 300 mg/day Headache, hypotension, reflex tachycardia, palpitations, fluid retention -Mitral valve rheumatic heart disease -CAD -DILE (dose and titration related) Isosorbide dinitrate *pref d for systolic HF Isosorbide mononitrate ( Imdur, Monoket ) *not in HF guidelines Start: mg TID-QID T Target: 120mg/day Start: IR: 10-20mg BID (at least 7 hours apart) ER: 30 mg QD Hypotension, headache, dizziness, lightheadedness, flushing, tolerance, syncope -Use with PDE-5 inhibitors and riociguat -tolerance, headache, hypotension Isosorbide dinitrate + Start: 1 tab (20/37.5 mg) Same as above - no nitrate tolerance 7

8 hydralazine ( Bidil ) TID Target: 2 tab TID - Hydralazine - can be used in patients who cannot tolerate ACE-I and ARBs due to poor renal function, angioedema or hyperkalemia - Bidil - indicated in self-identified black patients with NYHA class III or IV, who are symptomatic despite optimal treatment with ACE-I and beta blockers. Digoxin : Inhibits the Na+/K+/ATPase pump, which results in a (+) inotropic effect and increases CO. This agent also exerts a parasympathetic effect, which provides a (-) chronotropic effect, causing a decrease in HR Agent Dosing Contraindication Other Notes Digoxin ( Digitek, Digox, Lanoxin ) Typical dose: mg/day Therapeutic range for HF = ng/ml Ventricular Fibrillation Added in patients who remain symptomatic, despite receiving an ACE Inhibitor/ARB with a Beta-Blocker CrCl <50 ml/min: Decrease dose/frequency Improves symptoms, exercise tolerance, & QOL Antidote = DigiFab Does NOT improve survival of HF patients, but does reduce hospitalizations for HF - Warnings: 2nd/3rd degree heart block without a pacemaker, Vesicant, Wolff-Parkinson-White Syndrome with AFib - Side Effects: Mental disturbances; Headache; Dizziness; N/V/D - Monitoring: HR; EKG; BP; Electrolytes; Renal function; Digoxin level (drawn hours after dose) - Drug Interactions: - Monitor for bradycardia when used with other agents that can decrease HR (i.e., Beta-Blockers) - Decreased renal function requires a lower digoxin dose. Avoid in acute renal failure - Digoxin is a P-gp & CYP3A4 substrate - Levels increase when used with amiodarone, verapamil, clarithromycin, itraconazole, etc. - Reduce digoxin dose by 50% when used with amiodarone - Hypomagnesemia, Hypokalemia, and Hypercalcemia increase the risk of digoxin toxicity - Hypothyroidism can increase digoxin levels - Toxicity: - Initial S/S N/V; Bradycardia; Loss of appetite - Severe S/S Yellow/Green vision; Blurriness; Halos; Confusion; Abd Pain; Delirium; Prolonged PR interval; Arrhythmias Ivabradine: A hyperpolorization-activated cyclic nucleotide gated channel blocker that inhibits the funny current (I F ) in the sinus node reduction in sinus rate and heart rate. Reduces risk of hospitalization - no effect on mortality. Agent Dosing Side Effects Contraindications Warnings Ivabradine ( Corlanor ) Starting: 5 mg BID - adjust dose after 2 weeks based on HR Maintenance: mg BID Target: Resting HR between bpm Bradycardia, hypertension, a fib, luminous phenomena Acute decompensated HF, BP <90/50, sick sinus syndrome, sinoatrial block or 3rd degree AV block, resting HR <60 prior to treatment, severe hepatic impairment, pacemaker dependence; use Dec HR and bradycardia, which can increase QTc prolongation and ventricular arrhythmia risk, fetal toxicity, monitor for a fib 8

9 - Can be used as adjunctive therapy in patients: - With stable, symptomatic chronic HF - LVEF 35% - Sinus rhythm and resting HR 70 bpm - On max tolerated doses of BB or have contraindication to BB use - Drug Interactions - Ivabradine is a CYP 3A4 substrate - contraindicated with strong inhibitors - Other medications that decrease HR Potassium Oral Supplementation (Nick) with strong CYP3A4 inhibitor Agents Potassium Chloride ( Klor-Con, Klor-Con M20, Micro-K, Klor-Con 10, Klor-Con M10, Klor-Con M15, K-tab ) Dosing Prevention of Hypokalemia: meq/day in 1-2 divided doses Treatment of Mild Hypokalemia: meq/day in 2-5 divided doses (Adjusting dose according to lab values) - < meq should be given as a single dose to avoid GI discomfort - Contraindications: - Severe renal impairment - Hypokalemia - PO solid dosage forms are C/I in patients with delayed or obstructed passage through the GI tract - Warnings: Caution in patients with mild-moderate renal impairment, patients with disorders that alter K+ (i.e., Addison s disease), and in patients taking agents that can increase K+ - Side Effects: N/V/D; Abd pain; Hyperkalemia; Flatulence - Monitoring: ph; Urine Output; Cl-; Mg2+; K+ - Other Notes: - Take with meals and a full glass of water to minimize GI irritation - Micro-K : Capsules can be open contents can be sprinkled on applesauce/pudding and immediately swallowed - K-Tab, Klor-Con : - Swallow whole - Do NOT crush, chew, cut, or suck on tablets - Klor-Con M : - Swallow whole - Do NOT crush, chew, or suck on tablets - Tablets can be cut in half and swallowed, or can be dissolved in 4oz of water (stir x2 minutes and drink immediately) Long-Term Management of Heart Failure - Rehospitalization is common in patients with heart failure. Many readmissions are due to non-adherence with medications or lifestyle recommendations - Hospitals can be penalized by Medicare for readmission due to heart failure exacerbations 9

10 References 1. Yancy CW, Jessup M, Bozkurt B, et al ACC/AHA/HFSA Focused Update on the 2013 ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2017;136:e137-e Yancy CW, Jessup M, Bozkurt B, et al ACCF/AHA Guideline for the Management of Heart Failure. Circulation. 2013;128:e240-e327 10