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OVERVIEW OF TREATMENT OF CONGESTIVE HEART FAILURE

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OVERVIEW Background and Historical Perspective Determinants of Cardiac Output and Hemodynamic Intervention Newer Therapeutics

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EVOLUTION IN CONCEPTS Cardio-renal (pre 1970) : Digoxin, diuretics Hemodynamic 1970s and 1980s: + Inotropics, VD Neurohormonal 1990s: RAS, SNS

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DETERMINANTS OF CARDIAC PERFORMANCE HEART RATE CONTRACTILITY PRELOAD VASODILATOR THERAPY AFTERLOAD

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PRELOAD AFTERLOAD CONTRACTILITY RATE LV

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CO = SV x HR EF = CO

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HEART RATE COMPENSATORY RESPONSE ATROPHINE ISUPREL PACER

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CONTRACTILITY Inherent property of the myocardium Allows the heart to increase its extent and force of shortening independent of the Starling mechanism Not directly measurable

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CONTRACTILITY DIGITALIS DOBUTAMINE DOPAMINE ISUPREL EPINEPHRINE CALCIUM GLUCAGON AMIRANOME (Miliron)

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STARLINGS LAW THE MORE A MYOCARDIAL FIBER IS STRETCHED DURING DIASTOLE, THE MORE IT WILL SHORTEN IN SYSTOLE IT WILL ALSO SHORTEN WITH GREATER FORCE

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PRELOAD The length to which a cell is stretched prior. To the next contraction The volume or pressure generated in the ventricles at end-diastole Degree to which a cell is stretched in diastole (preload) force during systole

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AFTERLOAD IMPEDANCE OF BLOOD FROM THE VENTRICLE Determined by: The volume and mass of blood ejected from the ventricle The compliance and total cross-sectional area of the vascular space into which the blood is ejected.

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AFTERLOAD RESISTANCE PROXIMAL IMPEDENCE

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SYSTEMIC VASCULAR RESISTANCE SVR= (MAP-RAP) (80) CO MAP= MEAN ARTERIAL PRESSURE RAP= RIGHT ATRIAL PRESSURE CO= CARDIAC OUTPUT

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BASIC HEMODYNAMIC PARARMETERS Preload=PCWP Afterload=SVR

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LVEDP = LA = PVP = PCWP = PAP

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12 3 4

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12 3 4

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VASODILATOR DRUGS AGENTARTERIAL (Afterload) VENOUS (Preload) Nitropusside +++ Nitrates +++++ Hydralazine +++++ Prazosin ++ Nesiritide (Natrecor) +++++

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Clinical Profile of Nesiritide Vasodilation (venous > arterial) Rapidly improves symptoms of congestion Does not increase heart rate (decreases myocardial oxygen demand) Is not proarrhythimic Neurohormonal suppression (decreases aldosterone, endothelin-1) Mild diuresis/natriuresis

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Clinical Profile Nesiritide (cont.) No evidence of tachyphylaxis Symptomatic hyptension as low as 4% in the VMAC study Dosing convenience (bolus plus standard- dose IV infusion

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PATIENT PRESENTATION P.E.CXREKFBPOUTPUTR.A.P.A.PCWBNP SOBCHFST110/7020cc/hr1545/3030++ SOBCHFST210/12040cc/hr1545/3030++ SOBCHFST80/5020cc/hr1545/3030++ SOBCLEARST80/5020cc/hr1545/306+ LETHARGICCLEARST80/500225/43N SOBHAZYST110/7020cc/hr1545/2012+ UNCONCIOUSCHFVT60/4001545/3030+ ALERTCLEARMSR240/14020cc/hr830/1818+ ALERTCLEARMSR80/5020cc/hr2050/2012++ LETHARGICCLEARST80/5020cc/hr830/88N

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EVOLUTION IN CONCEPTS Cardio-renal (pre 1970): Digoxin, diuretics Hemodynamic 1970s and 1980s: + Inotropics, VD Neurohormonal 1990s: RAS, SNS

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CLINICAL APPROACH Control Volume (Rx Symptoms) Hemodynamic StabilitySlow Progression DiureticInotropic VasodilatorsNeurohormonal

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NEUROHORMONAL FACTORS IN HEART FAILURE PROGRESSION Circulating (RAS, SNS) Abnormality in regional blood flow, renal sodium retention Endothelin (ET-1, ET-2, ET-3) Vasoconstrictors Natriuretic Peptide, (ANP) Vasodilators, suppresses RAS Cytokines (TNF, Interleukin) Depresses contractility, anorexia and cachexia

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Neurohormonal Intervention in Heart Failure Heart Failure Renin- angiotensin system Sympathetic nervous system ACE inhibitionBeta Blockade

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ACE INHIBITORs (ANGIOTENSIN CONVERTING ENZYMES INHIBITORS) ACE INHIBITORs (ANGIOTENSIN CONVERTING ENZYMES INHIBITORS) GENERICBRAND NAME BENAZEPRILLOTENSIN CAPTOPRILCAPOTEN ENALAPRILVASOTEC FOSINOPRILMONOPRIL LISINOPRILZESTRIL, PRINIVIL MOESIPRILUNIVASC PERINDOPRILACEON QUINAPRILACCUPRIL RAMIPRILALTACE TRANDOLAPRILMAVIK ARBs (ANGIOTENSION RECEPTOR BLOCKERS) ARBs (ANGIOTENSION RECEPTOR BLOCKERS) GENERICBRAND NAME CADESARTANATACAND EPROSARTANTEVETEN IRBESARTANAVAPRO LOSARTANCOZAAR OLMESARTANBENICAR TELMISARTANMICARDIS VALSARTANDIOVAN

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BETA BLOCKERs GENERICBRAND NAME ACEBUTOLOLSECTRAL ATENOLOLTENORMIN BETAXOLOLKERLONE BISPROLOLZEBETA CARTEOLOLCARTROL ESMOLOLBREVIBLOC METOPROLOLLOPRESSOR, TOPROL NADOLOLCARGARD PENUTOLOLLEVATOL PINDOLOLVISKEN PROPRANOLOLINDERAL SOTALOLBETAPACE TIMOLOLBLOCADREN ALPHA AND BETA BLOCKERs GENERI9CBRAND CARVEDILOLCOREG LABETALOLNORMADINE, TRANDATE

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Effect of Carvedilol on Left Ventricular Ejection Fraction Patients receiving diuretics, ACE inhibitors, digoxin; follow-up 6 months; placebo (n=84), carvedilol (n=261). Mulitcenter Oral Carvedilol Heart Failure Assessment Adapted from Bristow et al. Circulation. 1996;94:2807-2816. P