Exacerbating or Precipitating Factors in Heart Failure (HF)® Cardiac Acute ischemia Arrhythmia Endocarditis Myocarditis Pulmonary embolus. Uncontrolled hypertension Valvular disorders Metab« Patient-Related Anemia Dietary/fluid nonadherence Hyperthyroidism/ HF therapy nonadherence thyrotoxicosis Use of cardiotoxins Infection (cocaine, chronic Pregnancy alcohol, amphetamines, Worsening renal —_ sympathomimetics) function Offending medications (NSAIDs, COX-2 inhibitors, steroids, lithium, B-blockers, calcium channel blockers, antiarrhythmics, alcohol, thiazolidinediones)Ww wiee2 ‘Beneficial nd Detrimental compen Response Troms prot hh (Siren Tween ee Cora 0S Senora erp an ets ofthe Compensatory Responses in Heart Fallure™” Bena ees ‘Ops ce olane ws om Sing mech sane apron nthe fpcof duced sae ou Sones compenstln Deviant et of Compensation non and water congston anced omeon| focesced 80, Inceed fern denen ste volume an further acthates iecorceton panes ‘Sronened doe ling ime Bnei dowrnaguton decreas ceptor sesitity Feprmten ovaries Ince mya cl oeth Distt dsuncion Sycie tinction ited a of myocar ei eth Iced a of myocar echema Ince ryt ieTable 6-1 Causes of Heart Failure Systolic Dysfunction (Decreased Contractility) + Reduction in muscle mass (eg, myocardial infarction) * Dilated cardiomyopathies * Ventricular hypertrophy « Pressure overload (eg, systemic or pulmonary hypertension, aortic or pulmonic valve stenosis) + Volume overload (eg, valvular regurgitation, shunts, high- output states) Diastolic Dysfunction (Restriction in Ventricular Filling) + Increased ventricular stiffness * Ventricular hypertrophy (eg, hypertrophic cardiomyopathy, pressure and/or volume overload) + Infiltrative myocardial diseases (eg, amyloidosis, sarcoidosis, endomyocardial fibrosis) + Myocardial ischemia and infarction * Mitral or tricuspid valve stenosis + Pericardial disease (eg, pericarditis, pericardial tamponade) Nonischemic Etiologies + Hypertension + Viral illness « Thyroid disease » Excessive alcohol use ‘Illicit drug use + Pregnancy-related heart disease + Familial congenital disease + Valvular disorders such as mitral or tricuspid valve regurgitation or stenosis From Parker RB, Nappi JM, Cavallari LH. Chronic heart failure. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: Pathophysiologic Approach, 10th ed. New York, NY: McGraw-Hill; 2017:80, with permissionCoe eens ene =P etn mectoemannne eactonsmpamicis | Chey plan Cosmos “ac a = Cate "Dp pda on een +P ena ep era wich sig et Some mae! en + bse 0) + rooworincuna pea + Hepa "eee tone “ene Pee «Gamat om “ptr coenees “tte Lamers +n = bergen ea 299m Memos or poD gc ar amt | aa bat3tpma = + Heocabogran (ECG My be otal ould shove Mri rurerous abnormal including acute S-wave changes = Nase from myocatlaischema, ail illaton bradycardia ond + Bloxing Lhyperwoohy + Ases + Serum cea: May be increased oning to hypoperfusion + Mera satus changes confuson, auction) (eceiin eral dtecionceicxninietobme + Weakness hate += Complete blood count Ueto determine HF due to satay reduced onynen-earying caps. + Insomn + Chest ray Use for detection cf cada enlargement, Signs pulmonay edema, and ples fusions + Pulmonary les + Echocadogame Usd oases LV soe vahe function rey eden gett ef wal mote abormsties ared ton +5, galopTable Drugs That May Precipitate or Exacerbate Heart Failure Negative Inotropic Effect + Antiarrhythmics (eg, disopyramide, flecainide, propafenone) « B-Blockers (eg, propranolol, metoprolol, carvedilol) * Calcium channel blockers (eg, verapamil, diltiazem) + Itraconazole Cardiotoxic + Doxorubicin * Epirubicin = Daunomycin « Cyclophosphamide * Trastuzumab + Bevacizumab * Mitoxantrone * Ifosfamide + Mitomycin + Lapatinib * Sunitinib + Imatinib + Ethanol » Amphetamines (eg, cocaine, methamphetamine) Sodium and Water Retention « NSAIDs + COX-2 inhibitors + Rosiglitazone and pioglitazone * Glucocorticoids * Androgens and estrogens « Salicylates (high dose) * Sodium-containing drugs (eg, carbenicillin disodium, ticarcillin disodium) Uncertain Mechanism + Adalimumab « Etanercept + Infliximab_ ad rug Dosing inthe Pharmacologic Treatmer tof Heart Faliure Usual Range Special Population Dose Comments pug Brand Name Intl Dose Loop Diuretics Hees Laie 20-40 mgance ot ‘we daly umstavide Sumer? 05-LOmgonce ot wae daly Tewsemide Demder? —10-20mgence diy AcE Inhibitors Ae capcte® 625 made tes ‘asiy raat Vsotect 25 mg wie aly Eimepm —_zeaeshinwer 25-50mgonce daly Ging Accupit Smo twcedaty Senet Ataces 128-23 Fesropd — Monapait™ — S-10mponcedtiy Tiandbapnt Mavi? ——-05-1Omgonce daily Pesindoprl Accent 2 mgence daily ‘Ansotensa Receptor Blockers Gyrsstan Agcanch = imgonce daly horan "lovee 20s mg ict daly Koren Caray 25-50 gence daly ‘Angiotensin Receptor Nepisin Inhibitor (ARND See eres aah ma seu! votaran olor ne sly pttocers Brora 125mgoncedaiy Coed asm once gay Canediol Cong eR mance ily shonoate (a Mitcoidal” Topeba* —125.25mgoxe ‘uct iy Aldosterone Receptor Antonis SRonstone Acton GPR SO mL ‘m3 125-25 mg once ay cxc120-50 min {033-083 mL) 1609 Exe ortiice daly crete 20min (033, rus 00mg daly cjet20-s0 mun a3 088mUs 29 {nce twice daly crcl 20min {Dasmust 8-109 aly crcl 20-S0 mun (033-08) 9409 ‘nce dy ciel 20min {35;nU5 200g day 29-160mgonceor rewce daly 10-80 eg once ely somgitvee tes ‘air ozo mace di dozamaonce sl Dnadmg twice daly og wee dy ‘dmg once ely Ama once 8-16 mg once day s2mgonce dy Teoma rece dae Tsomsancedsiy" 97/103 mg subi For patients taking low ‘asatantweeoseetornot ing an ai ‘etinbror or ARBorf CGiRiee 30mm 17a the tring dose ir 24/26 m9 soca taleartos twice aay 10 ma once eae Tonge defor patents ‘rcihing > 2549 (127 ®) 15d tice diy Big ice daly 0mm once day? oo mgonce day 25-50mg.oce die eGFR 30-49 ml/mev173 125 mg once daly o& vey other dy Single doses exceeding those ited are unity to etc. snidtonalespome Single doses exceeding those Tsted are ure tc eb sdstonaresponse Single does exceeding those ited ore unity to esc. tddtonalespomse Undergces bth hepatic are rena iranation Undergoes bath Pepa and Undegor bath bepaticand Discontinue AC initors atlas hours before ition sacabinitaran tester allow 36 ous between dscorsinuina Aes and starting ACE shestor ‘Toke with fond Take with ood The rk of ypeaemia Fheeases serum creatinine eS 16mg/d (at yn). vod bscine posi eS méqi irmort) (ConinveOA (Ir_— SESS Intravenous Diuretics Used to Treat Heart Fllure-Relate Fluid Retention Onset of Action Duration of Action Intermittent Solas Continuous Infusio (minutes) (hours) Relative Poteney Dosing tg) Dosing (balusinfusion) fucsemee 25 6 © 20-2004 m-40725-10, fumetane 23 ra a rio i051 Bocrmesed 515 2 5-1 mag per doseCentral venous (right atrial) Pressure, mean Right ventricular pressure Pulmonary artery pressure Pulmonary artery pressure, mean Pulmonary artery occlusion pressure, mean? Systemic arterial pressure Mean arterial pressure Cardiac output Cardiac index Stroke volume index Systemic vascular resistance Pulmonary vascular resistance Arterial oxygen content Mixed venous oxygen content Arteriovenous oxygen content difference Normal Value <5 mm Hg? (0.7 kPa) 25/0 mm Hg? 25/10 mm Hg? < 18 mm Hg} (24 kPa) < 12 mm Hg} (1.6 kPa) 120/80 mm Hg? 70-110 mm Hg? (9.3-14.6 kPa) 4-6 L/min (0.07-0.10 L/s) 2.8-4.2 L/min/m? (0.047-0.070 /s/m?) 30-65 mL/beat/m® (0.030-0.065 L-beat"m) 900-1400 dynscm-* (90-140 MPasm-) 150-250 dynscm* (15-25 MPasm™) 20 mL/dL¢ (200 mU/L) 15 mL/dL: (150 mU/L) 3-5 mL/dL< (30-50 mU/L) —— >1 mm Hg = 0.133 kPa; 1 mL/beat per square meter = 0.001 Lbeat-m?. ®also referred to as pulmonary artery wedge pressure (PCWP) 1 dyn-s-cm = 0.1 MPas-m-=3; 1 mL/dL = 10 mU/L. From Rodgers JE, Reed BN. Acute decompensated heart failure. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 10th ed. New York, NY: McGraw-Hill; 2017:121, with permission.d “Laue abdicate ‘Subset | (Warm and Dry) + Clagreater than 2.2 Umin/r’ (0.037 Lis/mn’), PCWP less than 18 mm Hg (24 KPa) + Patients considered well compensated and perfused, ‘without evidence of congestion «+ No immediate interventions necessary except optimizing ‘oral medications and monitoring ‘Subset Il (Warm and Wet) + Clagreater than 2.2 L/min/m’ (0.037 L/s/m’), PCWP greater than oF equal to 18 mm Hg (24 KPa) + Patients adequately perfused and display signs and symptoms of congestion ‘+ Main goal is to reduce preload (PCWP) carefully with loop dliureties and vasodilators ‘Subset Ill (Cool and Dry) ‘= Clless than 2.2 L/min/m? (0.037 L/s/mn"), WP less than 121mm Hg (24 KPa) + Patients are inadequately perfused and not congested ‘+ Hypoperfusion leads to increased mortality elevating death rates fourfold compared with thase who are adequately perfused + Treatment focuses on increasing CO with positive inotropic agents and/or replacing intravascular fluids + Fluid replacement must be performed cautiously because patients can rapidly become congested ‘Subset IV (Cool and Wet) «+ Clless han 2.2 Limind/im? (0037 Lis’), POP greater than 18 rm Hig (24 kPa) + Patients are inadequately perfused and congested + Classified as the most complicated clinical presentation of AHF with the worst prognosis ‘+ Most challenging to teat; therapy targets alleviating signs and symptoms of congestion by increasing Cl.as well as reducing POWP while maintaining adequate mean arterial pressure + Treatment involves a delicate balance between diuretics, ‘vasodilators, and inotropic agents + Use of vasopressors is sometimes necessary to maintain BPDoble ‘Drug Dosing in the Pharmacologic Treatment of Hear Failure (Continued) rug Brand Name Intl Dose Usual Range Special Population Dose_Comments EplerenoneInspa® «GFR SOUS mg oncedniy eGFR30-19 m/min’ The of hypetaleals rmivi73 25mg T7sm:25mgeray nesses Seu cresting ‘once diy ater oy 5 tsmg/d (141 pmol) ‘ood foie potasiom ‘SESimEqh (mmol) commer Rydlaine- ett ydalaine 375mg Hytlasine 75 mg Irate in conjunction Veovobide tives times diye" Aves times das ‘ith sandord hea fle Dine howobide deate lororbide detate therapy 0 improve sual 30g tee nes" a0 rmgtnee nes Seduce hexptatntens ‘aly ‘aig ‘strident Avcan- econ pater Dgnkn——Laroxint*_——-0125-025mgonce 0125-025 mg.once Reduce dosein dey Target pasa concentation aay diy fies thon lean range 405-09 ng/mL Eedymoss andpaterss regi: 06-12 pmol) vithimpatedrenal Does not improve sual Iunenon Impaverts with HEP habasine Colne” Smgtwice daly 5-7Smgtwice daily Avo resting haat ate esatedto reset kof ‘60 BP belo hospizaton in pacers ‘eatment ‘tnt bo oe ‘normale yen resting eat te» 708M ‘oleate Blecher doses, Take wh messrug Monitoring Drug Class _ Adverse fect Monitoring Parameters Comments ACE oaloedems cough hyperaiema, BR dacuojes BUN, Conaiadcated in pales ith Bltal eal any lebtos "Iyptersion, eral dytancion and creatinine ‘Senos, history of ansiedema, oe pesnancy. Sess BRBUN. creatinine andelcytesat baseline and 1-2 wes ter tation ov tease in dose Gas get dose fom cncal ras ox highest toed. ‘Angiotensin Hypedaleni hypotension, Recoytes UN, __Convoindate inpatients wth bial vena artery receptor renaldystunton ee erestrane eno or pregnancy. Asses BUN. cet, 3d blockers tetris at Bastin an 1-2 week ater eon (86) bricreasein dove, Usewth caution nates tha Fistor of ACE inhibitor szocstedangaedema Goal Target dove tm cincaltiasor highest tlerated Socubiv” —Aagoedemahypetatemia, ——_-BRekewoltes SUN, Conia in patents ith a ator of anpoeder> vakartan"“ypotersion dzzness eral andeeatane SSsocted with ACE nha ARB heap on Syincion Breqniny Assets BE BUN, creatinine, and ces [rbmling and 1-2 ess after intaten or nereae those tr with sow dove and double the dove exe 20% gcse eerste seed on B erum poem, and ‘ena faction Gos target dose from lial ls or highest tleated Adstrone Gynecomasa/breasttendermes) BR eecvalites SUN, Aes BUN, cretnine and slecuo\tes 3 bassine receptor menus inequarie ‘od creatine (Checkpotasten 3 oy ar | week afterntiston and Snagensts Gptoaclaconehypetalemia, then monthly fr heist sont then every 3 maths worsening renal funtion Change to eperenonefgynecomatia develops with spionalactone Blockers aches, heart block, BRHRECG. sons Sart wih ow doseand trate upward no mare ten Tronchosgasm Pypotension and symgiomsof than every 2 weeks stleated based on BHR and worsening HF “worsening Hr blood symptoms Go toe cove rom ical or ighest diaose {Oletated. Patients may fee! worse before ey feel betes, Digan Gland CNS adverse brady Electohes BUN, Target sum digonnconcentation 05-09 ng/n, ‘sr scythe Creatine ECG tum eghs06-13 ene. ‘digo concentaton abeadine —Gracheaca hypatenien atrial BRR ECE Stat th 5g tie ey andar wea aust ose fin linus phenomena to achieve aesing MR 30-60% Only use patents in (phorphenes vaneanty sinus yh enhonced brightest 9 potion Fhe vl eld Diuretics Hypowalemianygotenson, «BR eecwojtes SUN, Dose should be adjusted based on volume tats onl Fypanaveria hypokalemia, creatine ghucose, function, elecvoyes and BP assess these pavametes Fypamagrosemia ypetutcema, urea changesin Te Weck ter dose changes Goals loves dase that tenaloysunction tht eh M0 rmantans ewer Hydalaine Hypotension headache ash, BR HE arthralgia pus acy Nets Hypotension headache, ee Teohtbeodesnese