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Chronic chf

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Chronic chf

  1. 1. CHRONIC CONGESTIVEHEART FAILUREAmerican Heart Associationin collaboration withSociedad Española de Cardiologia June, 1999
  2. 2. Chronic Congestive Heart FailureCommittee on Post Graduate Education,Council on Clinical Cardiology,American Heart AssociationDeveloped in collaboration with theSociedad Española de CardiologiaPrepared by:Ann F. Bolger, MDJosé Lopez Sendón, MDThe content of these slides is current as of June, 1999. (Slide #62 updated 9/00)Future revisions will be posted on theAmerican Heart Association website (www.americanheart.org).
  3. 3. Chronic Congestive Heart Failure DEFINITION“The situation when the heart isincapable of maintaining a cardiacoutput adequate to accommodatemetabolic requirements and thevenous return." E. Braunwald
  4. 4. Chronic Congestive Heart Failure EVOLUTION OF CLINICAL STAGES NORMALNo symptomsNormal exerciseAsymptomaticNormal LV fxn LV Dysfunction No symptoms Compensated Normal exercise Abnormal LV fxnCHF Decompensated No symptoms Exercise CHF Abnormal LV fxn Symptoms Refractory Exercise CHF Abnormal LV fxn Symptoms not controlled with treatment
  5. 5. Chronic Congestive Heart Failure DETERMINANTS OF VENTRICULAR FUNCTION CONTRACTILITY PRELOAD AFTERLOAD STROKE VOLUME- Synergistic LV contraction- LV wall integrity HEART- Valvular competence RATE CARDIAC OUTPUT
  6. 6. Chronic Congestive Heart FailureTREATMENT OBJECTIVES Survival Morbidity Exercise capacity Quality of life Neurohormonal changes Progression of CHF Symptoms
  7. 7. Chronic Congestive Heart Failure TREATMENTCorrection of aggravating factorsPregnancy EndocarditisArrhythmias (AF) ObesityInfections HypertensionHyperthyroidism Physical activityThromboembolism Dietary excess MEDICATIONS
  8. 8. Chronic Congestive Heart Failure TREATMENTPHARMACOLOGIC THERAPY DIURETICS INOTROPES VASODILATORS NEUROHORMONAL ANTAGONISTS OTHERS (Anticoagulants, antiarrhythmics, etc)
  9. 9. Chronic Congestive Heart Failure DRUGS HEMODYNAMIC EFFECTS Normal A IStroke A+VVolume V D CHF Ventricular Filling Pressure
  10. 10. Chronic Congestive Heart FailurePHARMACOLOGIC THERAPY Improved Decreased Prevention Neurohumoral symptoms mortality of CHF Control DIURETICS yes ? ? NO DIGOXIN yes = minimal yes INOTROPES yes mort. ? noVasodil.(Nitrates) yes yes ? no ACEI yes YES yes YESOther neurohormonalcontrol drugs yes +/- ? YES
  11. 11. Chronic Congestive Heart Failure TREATMENTNormal Asymptomatic LV dysfunction EF <40% Symptomatic CHF ACEI NYHA II Symptomatic CHF Diuretics mild NYHA - III Neurohormonal Symptomatic CHF Loop inhibitors NYHA - IV Diuretics Digoxin? Inotropes Specialized therapy Transplant Secondary prevention Modification of physical activity
  12. 12. Chronic Congestive Heart Failure DIURETICS ThiazidesCortex Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle K-sparing Inhibit reabsorption of Na in the distal convoluted and collecting tubule Loop diureticsMedulla Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of Henle Loop of Henle Collecting tubule
  13. 13. Chronic Congestive Heart Failure THIAZIDES MECHANISM OF ACTION Excrete 5 - 10% of filtered Na+ Elimination of K Inhibit carbonic anhydrase: increase elimination of HCO3 Excretion of uric acid, Ca and Mg No dose - effect relationship
  14. 14. Chronic Congestive Heart Failure LOOP DIURETICS MECHANISM OF ACTION Excrete 15 - 20% of filtered Na+ Elimination of K+, Ca+ and Mg++ Resistance of afferent arterioles - Cortical flow and GFR - Release renal PGs - NSAIDs may antagonize diuresis
  15. 15. Chronic Congestive Heart FailureK-SPARING DIURETICSMECHANISM OF ACTION Eliminate < 5% of filtered Na+ Inhibit exchange of Na+ for K+ or H+ Spironolactone = competitive antagonist for the aldosterone receptor Amiloride and triamterene block Na+ channels controlled by aldosterone
  16. 16. Chronic Congestive Heart FailureDIURETIC EFFECTS Volume and preload Improve symptoms of congestion No direct effect on CO, but excessive preload reduction may Improves arterial distensibility Neurohormonal activation Levels of NA, Ang II and ARP Exception: with spironolactone
  17. 17. Chronic Congestive Heart Failure DIURETICS ADVERSE REACTIONS Thiazide and Loop Diuretics Changes in electrolytes: Volume Na+, K+, Ca++, Mg++ metabolic alkalosis Metabolic changes: glycemia, uremia, gout LDL-C and TG Cutaneous allergic reactions
  18. 18. Chronic Congestive Heart Failure DIURETICS ADVERSE REACTIONS Thiazide and Loop DiureticsIdiosyncratic effects: Blood dyscrasia, cholestatic jaundice and acute pancreatitisGastrointestinal effectsGenitourinary effects: Impotence and menstrual crampsDeafness, nephrotoxicity
  19. 19. Chronic Congestive Heart Failure DIURETICS ADVERSE REACTIONS K-SPARING DIURETICS Changes in electrolytes: Na+, K+, acidosis Musculoskeletal: Cramps, weakness Cutaneous allergic reactions : Rash, pruritis
  20. 20. Chronic Congestive Heart Failure DIGOXIN Na-K ATPase Na-Ca Exchange + Na K + Na+ Ca++ Myofilaments Ca++ K+ Na+ CONTRACTILITY
  21. 21. Chronic Congestive Heart Failure DIGOXINPHARMACOKINETIC PROPERTIES Oral absorption (%) 60 - 75 Protein binding (%) 25 Volume of distribution (l/Kg) 6 (3-9) Half life 36 (26-46) h Elimination Renal Onset (min) i.v. 5 - 30 oral 30 - 90 Maximal effect (h) i.v. 2-4 oral 3-6 Duration 2 - 6 days Therapeutic level (ng/ml) 0.5 - 2
  22. 22. Chronic Congestive Heart Failure DIGOXIN DIGITALIZATION STRATEGIES Maintenance Loading dose (mg) Dose i.v oral 12-24 h oral 2-5 d (mg)0.5 + 0.25 / 4 h 0.75 + 0.25 / 6 h 0.25 / 6-12 h 0.125-0.5 / d ILD: 0.75-1 1.25-1.5 1.5-1.75 0.25 / d ILD = average INITIAL dose required for digoxin loading
  23. 23. Chronic Congestive Heart Failure DIGOXIN HEMODYNAMIC EFFECTS Cardiac output LV ejection fraction LVEDP Exercise tolerance Natriuresis Neurohormonal activation
  24. 24. Chronic Congestive Heart Failure DIGOXIN NEUROHORMONAL EFFECTS Plasma Noradrenaline Peripheral nervous system activity RAAS activity Vagal toneNormalizes arterial baroreceptors
  25. 25. Chronic Congestive Heart Failure DIGOXINEFFECT ON CHF PROGRESSION 30 Placebo n=93 % DIGOXIN Withdrawal WORSENING 20 OF0.5 mg /dDIGOXIN: 0.125 - CHF p = 0.001(0.7 - 2.0 ng/ml) 10EF < 35%Class I-III (digoxin+diuretic+ACEI)Also significantly decreased exercisetime and LVEF. DIGOXIN n=85 0 RADIANCE 0 20 40 60 80 100 N Engl J Med 1993;329:1 Days
  26. 26. Chronic Congestive Heart Failure OVERALL MORTALITY 50 40 30 % Placebo 20 n=3403 p = 0.8 10 DIGOXIN n=3397 0DIG 0 12 24 36 48N Engl J Med 1997;336:525 Months
  27. 27. Chronic Congestive Heart Failure DIGOXIN LONG TERM EFFECTS Survival similar to placebo Fewer hospital admissions More serious arrhythmias More myocardial infarctions
  28. 28. Chronic Congestive Heart Failure DIGOXIN CLINICAL USES AF with rapid ventricular response CHF refractory to other drugs Other indications? Can be combined with other drugs
  29. 29. Chronic Congestive Heart Failure DIGOXIN CONTRAINDICATIONS ABSOLUTE: - Digoxin toxicity RELATIVE - Advanced A-V block without pacemaker - Bradycardia or sick sinus without PM - PVC’s and TV - Marked hypokalemia - W-P-W with atrial fibrillation
  30. 30. Chronic Congestive Heart Failure DIGOXIN TOXICITYCARDIAC MANIFESTATIONS ARRHYTHMIAS : - Ventricular (PVCs, TV, VF) - Supraventricular (PACs, SVT) BLOCKS: - S-A and A-V blocks CHF EXACERBATION
  31. 31. Chronic Congestive Heart Failure DIGOXIN TOXICITY EXTRACARDIAC MANIFESTATIONS GASTROINTESTINAL: - Nausea, vomiting, diarrhea NERVOUS: - Depression, disorientation, paresthesias VISUAL: - Blurred vision, scotomas and yellow-green vision HYPERESTROGENISM:
  32. 32. Chronic Congestive Heart FailurePOSITIVE INOTROPES CARDIAC GLYCOSIDES SYMPATHOMIMETICS Catecholamines ß-adrenergic agonists PHOSPHODIESTERASE INHIBITORS Milrinone Amrinone Piroximone Enoximone
  33. 33. Chronic Congestive Heart Failureß-ADRENERGIC STIMULANTS CLASSIFICATION B1 Stimulants Increase contractility Dobutamine Doxaminol Xamoterol Butopamine Prenalterol Tazolol B2 Stimulants Produce arterial vasodilatation and reduce SVRPirbuterol Rimiterol TretoquinolTerbutaline SoterenolCarbuterolFenoterol Salbutamol SalmefamolQuinterenol Mixed Dopamine
  34. 34. Chronic Congestive Heart Failure DOPAMINE AND DOBUTAMINE EFFECTS DA (µg / Kg / min) Dobutamine <2 2-5 >5Receptors DA1 / DA2 ß1 ß1 + α ß1Contractility ± ++ ++ ++Heart Rate ± + ++ ±Arterial Press. ± + ++ ++Renal perfusion ++ + ± +Arrhythmia - ± ++ ±
  35. 35. Chronic Congestive Heart Failure POSITIVE INOTROPES CONCLUSIONS May increase mortality Safer in lower doses Use only in refractory CHF NOT for use as chronic therapy
  36. 36. Chronic Congestive Heart Failure VASODILATOR DRUGS PRINCIPLES Normal Contractility Normal ContractilityCO VV AV Diminished Diminished Contractility Contractility PRELOAD AFTERLOAD
  37. 37. Chronic Congestive Heart Failure VASODILATORS CLASSIFICATION VENOUS Venous Vasodilatation Nitrates Molsidomine MIXED Calcium antagonists α-adrenergic Blockers ACEI Angiotensin II inhibitors K+ channel activators Nitroprusside Arterial ARTERIALVasodilatation Minoxidil Hydralazine
  38. 38. Chronic Congestive Heart Failure NITRATES HEMODYNAMIC EFFECTS1- VENOUS VASODILATATION Pulmonary congestion Ventricular size Preload Vent. Wall stress MVO22- Coronary vasodilatation Myocardial perfusion • Cardiac output3- Arterial vasodilatation • Blood pressure Afterload
  39. 39. Chronic Congestive Heart Failure NITRATES FUNCTIONAL CAPACITY 400 n=24 392 384 ** ** EXERCISE 300 267 TIME, seconds 200 100 Control 1ST 4 dose weeksJansen W et al ISOSORBIDE 5 - MONONITRATEMed Welt 1982;33:1756 20 mg / 8h
  40. 40. Chronic Congestive Heart Failure NITRATES 0.7 SURVIVAL Placebo (273) 0.6 Prazosin (183) Hz + ISDN (186) 0.5PROBABILITY 0.4OF 0.3DEATH 0.2 0.1 0VHefT-1 0 6 12 18 24 30 36 42N Engl J Med 1986;314:1547 MONTHS
  41. 41. Chronic Congestive Heart Failure NITRATES TOLERANCE " Decrease in the effect of a drug when administered in a long-acting form"Develops with all nitratesIs dose-dependentDisappears in 24 h. after stopping the drugTolerance can be avoided - Using the least effective dose - Creating discontinuous plasma levels
  42. 42. Chronic Congestive Heart Failure NITRATES TOLERANCECan be avoided or minimized - Intermittent administration - Use the lowest possible dose - Intersperse a nitrate-free intervalAllow peaks and valleys in plasma levels - Vascular smooth muscle recovers its nitrate sensitivity during the nadirs - Patches: remove after 8-10 h
  43. 43. Chronic Congestive Heart Failure NITRATES TOLERANCE H T A s.l. NTG O L L F ISDN E R L I 5-MN A I N F Percutaneous NTG C E E
  44. 44. Chronic Congestive Heart Failure NITRATES CONTRAINDICATIONS Previous hypersensitivity Hypotension ( < 80 mmHg) AMI with low ventricular filling pressure 1st trimester of pregnancy WITH CAUTION: Constrictive pericarditis i Intracranial hypertension e Hypertrophic cardiomyopathy
  45. 45. Chronic Congestive Heart Failure NITRATES CLINICAL USESPulmonary congestionOrthopnea and paroxysmal nocturnaldyspneaCHF with myocardial ischemiaIn acute CHF and pulmonary edema:NTG s.l. or i.v.
  46. 46. Chronic Congestive Heart Failure ACEI MECHANISM OF ACTIONVASOCONSTRICTION VASODILATATION ALDOSTERONE PROSTAGLANDINS VASOPRESSIN Kininogen tPA SYMPATHETIC Kallikrein Angiotensinogen RENIN Angiotensin I BRADYKININ A.C.E. Inhibitor Kininase IIANGIOTENSIN II Inactive Fragments
  47. 47. Chronic Congestive Heart Failure ACEI HEMODYNAMIC EFFECTS Arteriovenous Vasodilatation - PAD, PCWP and LVEDP - SVR and BP - CO and exercise tolerance No change in HR / contractility MVO2 Renal, coronary and cerebral flow Diuresis and natriuresis
  48. 48. Chronic Congestive Heart Failure ACEI FUNCTIONAL CAPACITY 100No 95 QuinaprilAdditional continued n=114 90Treatment p<0.001Necessary 85(%) Quinapril 80 stopped Placebo Class II-III n=110 75 2 4 6 8 10 12 14 16 18 20Quinapril Heart Failure TrialJACC 1993;22:1557 Weeks
  49. 49. Chronic Congestive Heart Failure ACEI ADVANTAGESInhibit LV remodeling post-MIModify the progression of chronic CHF - Survival - Hospitalizations - Improve the quality of lifeIn contrast to others vasodilators,do not produce neurohormonal activationor reflex tachycardia
  50. 50. Chronic Congestive Heart Failure ACEI SURVIVAL 0.8 0.7 Placebo 0.6PROBABILITY 0.5 p< 0.001OF 0.4 p< 0.002DEATH 0.3 Enalapril 0.2 0.1 0 CONSENSUS 0 1 2 3 4 5 6 7 8 9 10 11 12 N Engl J Med 1987;316:1429 MONTHS
  51. 51. Chronic Congestive Heart Failure ACEI SURVIVAL 50 p = 0.30 Placebo 40 n=2117 % 30 MORTALITY 20 Enalapriln = 4228 10 n=2111No CHF symptomsEF < 35 0 0 6 12 18 24 30 36 42 48SOLVD (Prevention)N Engl J Med 1992;327:685 Months
  52. 52. Chronic Congestive Heart Failure ACEI SURVIVAL 50 p = 0.0036 Placebo 40 n=1284 % 30 MORTALITY Enalapril 20 n=1285n = 2589CHF 10- NYHA II-III- EF < 35 0 0 6 12 18 24 30 36 42 48SOLVD (Treatment)N Engl J M 1991;325:293 Months
  53. 53. Chronic Congestive Heart Failure ACEI SURVIVAL 30 Asymptomatic ventricular Placebo dysfunction post MI n=1116 20 Mortality, Captopril n=1115 % 10n = 22313 - 16 days post AMIEF < 40 ² -19%12.5 --- 150 mg / day p=0.019SAVE 0N Engl J Med 1992;327:669 0 1 2 3 4 Years
  54. 54. Chronic Congestive Heart Failure ACEI SURVIVAL POST MI ACEI Benefit Pt SelectionISIS-4 Captopril 0.5 / 5 wk All with AMIGISSI-3 Lisinopril 0.8 / 6 wk All with AMISAVE Captopril 4.2 / 3.5 yr EF < 40 asymptomaticSMILE Zofenopril 4.1 / 1 yr Ant. AMI, No TRLTRACE Trandolapril 7.6 / 3 yr Vent Dysfx / Clinical CHF EF < 35AIRE Ramipril 6 / 1 yr Clinical CHF
  55. 55. Chronic Congestive Heart Failure ACEI INDICATIONS Clinical cardiac insufficiency - All patients Asymptomatic ventricular dysfunction - LVEF < 35 %
  56. 56. Chronic Congestive Heart Failure ACEI UNDESIRABLE EFFECTS Inherent in their mechanism of action - Hypotension - Dry cough - Hyperkalemia - Renal Insuff. - Angioneurotic edema Due to their chemical structure - Cutaneous eruptions - Neutropenia, - Dysgeusia thrombocytopenia - Proteinuria - Digestive upset
  57. 57. Chronic Congestive Heart Failure ACEI CONTRAINDICATIONS Renal artery stenosis Renal insufficiency Hyperkalemia Arterial hypotension Intolerance (due to side effects)
  58. 58. Chronic Congestive Heart Failure ANGIOTENSIN II INHIBITORS MECHANISM OF ACTION RENINAngiotensinogen Angiotensin I ACE Other paths ANGIOTENSIN II AT1RECEPTORBLOCKERS AT1 RECEPTORS AT2Vasoconstriction Proliferative Vasodilatation Antiproliferative Action Action
  59. 59. Chronic Congestive Heart Failure AT1 RECEPTOR BLOCKERS DRUGS Losartan Valsartan Irbersartan Candersartan Competitive and selective blocking of AT1 receptors
  60. 60. Chronic Congestive Heart FailureALDOSTERONE INHIBITORS Spironolactone ALDOSTERONECompetitive antagonist of thealdosterone receptor(myocardium, arterial walls, kidney) Retention Na+ Collagen Edema deposition Retention H2O Fibrosis Excretion K+ Arrhythmias - myocardium Excretion Mg2+ - vessels
  61. 61. Chronic Congestive Heart FailureALDOSTERONE INHIBITORSINDICATIONSFOR DIURETIC EFFECT• Pulmonary congestion (dyspnea)• Systemic congestion (edema) FOR ELECTROLYTE EFFECTS • Hypo K+, Hypo Mg+ • Arrhythmias • Better than K+ supplements FOR NEUROHORMONAL EFFECTS
  62. 62. Chronic Congestive Heart Failure ALDOSTERONE INHIBITORS CONTRAINDICATIONS • Hyperkalemia • Severe renal insufficiency • Metabolic acidosis
  63. 63. Chronic Congestive Heart Failureß-ADRENERGIC BLOCKERSPOSSIBLE BENEFICIAL EFFECTS Density of ß1 receptors Inhibit cardiotoxicity of catecholamines Neurohormonal activation HR Antihypertensive and antianginal Antiarrhythmic Antioxidant
  64. 64. Chronic Congestive Heart Failure ß BLOCKERS 50 SURVIVAL 40 ß Blocker Placebo 30 % 20 10 0 < 30% 30-40% > 40%BHATJACC 1990;16:1327 LV EJECTION FRACTION
  65. 65. Chronic Congestive Heart Failure ß BLOCKERS Mortality ß BLOCKER n=2231 YES No Yes 13.3% 24.3% ACEI No 19.5% 27.7%SAVECirculation 1995;92:3132
  66. 66. Chronic Congestive Heart Failure ß BLOCKERS CARVEDILOL4 studies in U.S.;1 in Australia/New ZealandU.S. studies with control groupMortality with Placebo 8.2% p < 0.0001Mortality with Carvedilol 2.9%Initial low doses, progressive
  67. 67. Chronic Congestive Heart Failureß-ADRENERGIC BLOCKERSINDICATIONS and UTILIZATION Not clearly established Begin with very low doses Slow augmentation of dose Slow withdrawal ?
  68. 68. Chronic Congestive Heart Failure ß-ADRENERGIC BLOCKERS IDEAL CANDIDATE? Suspected adrenergic activation Arrhythmias Hypertension Angina
  69. 69. Chronic Congestive Heart Failure ß-ADRENERGIC BLOCKERS CONTRAINDICATIONS Hypotension: BP < 100 mmHg Bradycardia: HR < 50 bpm Clinical instability Chronic bronchitis, ASTHMA Severe chronic renal insufficiency
  70. 70. Chronic Congestive Heart FailureCALCIUM ANTAGONISTS POTENTIAL EFFECTS Antiischemic Peripheral Vasodilatation Inotropy
  71. 71. Chronic Congestive Heart Failure CALCIUM ANTAGONISTS POSSIBLE UTILITYDiltiazem contraindicatedVerapamil and Nifedipinenot recommendedVasoselective (amlodipine, nisoldipine),may be useful in ischemia + CHFAmlodipine may be useful in nonischemic CHF
  72. 72. Chronic Congestive Heart FailureANTICOAGULANTS PREVIOUS EMBOLIC EPISODE ATRIAL FIBRILLATION Identified thrombus LV Aneurysm (3-6 mo post MI) Class III-IV in the presence of: - EF < 30 - Aneurysm or very dilated LV Phlebitis Prolonged bed rest
  73. 73. Chronic Congestive Heart FailureANTIARRHYTHMICSSustained VT, with/without symptoms - ß Blockers - AmiodaroneSudden death from VF - Consider implantable defibrillator
  74. 74. Chronic Congestive Heart Failure ANTIARRHYTHMICS MORTALITY 15 13.6 ns 13.7 MORTALITY AT 2 YEARS 10 %n=14865-21d post MIAmiodarone 5200 mg/dFollow up 1 - 4 years 101 / 743 102 / 743 0 EMIATAm Coll Cardiol 1996 Placebo Amiodarone
  75. 75. Chronic Congestive Heart FailureAmerican Heart Associationin collaboration withSociedad Española de CardiologiaCHRONIC CONGESTIVEHEART FAILUREThe content of these slides is current as of June, 1999.Future revisions will be posted on theAmerican Heart Association website (www.americanheart.org)

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