1. OVERVIEW OF TREATMENT OF CONGESTIVE HEART FAILURE

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

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

4. DETERMINANTS OF CARDIAC PERFORMANCE HEART RATE CONTRACTILITY PRELOAD VASODILATOR THERAPY AFTERLOAD

5. PRELOAD AFTERLOAD CONTRACTILITY RATE LV

6. CO = SV x HR EF = CO

7. HEART RATE COMPENSATORY RESPONSE ATROPHINE ISUPREL PACER

8. 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

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

10. STARLING’S LAW THE MORE A MYOCARDIAL FIBER IS STRETCHED DURING DIASTOLE, THE MORE IT WILL SHORTEN IN SYSTOLE IT WILL ALSO SHORTEN WITH GREATER FORCE

11. 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

14. 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.

15. AFTERLOAD – RESISTANCE PROXIMAL IMPEDENCE

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

17. BASIC HEMODYNAMIC PARARMETERS Preload=PCWP Afterload=SVR

18. LVEDP = LA = PVP = PCWP = PAP 

20. 12 3 4

21. 12 3 4

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

23. 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

24. 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

25. 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

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

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

29. 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 

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

35. 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

36. 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

38. 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<.05 vs placebo.

39. DRYWET WARM COLD CLINICAL ASSESSMENT Warm vs. Cold (Perfusion)- Pulse Pressure Dry vs. Wet (Congestion)- Jugular Venus Pressure

40. Rapid Assessment of Hemodynamic Status Congestion at Rest Low Perfusion At Rest NO YES Signs/symptoms of Congestion: Orthopnea/ PND JV Distension Hepatomegaly Edema Rates (rare in chronic heart failure) Elevated est. PA systolic Valsalva square wave NO A Warm & Dry B Warm & Wet YES (Low Profile) L Cold & Dry (Complex) C Cold & Wet Possible Evidence of Low Perfusion: Narrow pulse pressure Sleepy/obtunded Low Serum sodium Cool extremities Hypotension with ACE inhibitor Renal Dysfunction (one cause)

41. Profiles and Therapies of Advanced Heart Failure Congestion at Rest Low Perfusion At Rest NOYES Vasodilators Nitroprusside Nitroglycerine Nesiritied NO Warm & Dry PCW and CI Normal Warm & Wet PCW elevated CI normal YES Cold and Dry PCW low/normal CI decreased Cold & Wet PCW elevated CI decreased NI SVR High SVR Inotropic Drugs Dobuamine Milrinone Calcium Sensitizers

42. WARM UP THEN DRY OUT DRY WET WARM 1. Diuretics 2. Vasodilators COLD 1. Vasodilators 2. Positive Inotropics 1. Positive Inotropics 2. Vasodilators 3. Diuretics

43. NEWER THERAPEUTICS I. Biventricular Pacing I. EECP I. Measurement of BNP levels