1 / 75

CHRONIC CONGESTIVE HEART FAILURE American Heart Association in collaboration with

CHRONIC CONGESTIVE HEART FAILURE American Heart Association in collaboration with Sociedad Española de Cardiologia June, 1999. Committee on Post Graduate Education, Council on Clinical Cardiology, American Heart Association Developed in collaboration with the

may-mason
Download Presentation

CHRONIC CONGESTIVE HEART FAILURE American Heart Association in collaboration with

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CHRONIC CONGESTIVE HEART FAILURE American Heart Association in collaboration with Sociedad Española de Cardiologia June, 1999

  2. Committee on Post Graduate Education, Council on Clinical Cardiology, American Heart Association Developed in collaboration with the Sociedad Española de Cardiologia Prepared by: Ann F. Bolger, MD José Lopez Sendón, MD The content of these slides is current as of June, 1999. (Slide #62 updated 9/00) Future revisions will be posted on the American Heart Association website (www.americanheart.org).

  3. DEFINITION “The situation when the heart is incapable of maintaining a cardiac output adequate to accommodate metabolic requirements and the venous return." E. Braunwald

  4. Chronic Congestive Heart Failure EVOLUTION OF CLINICAL STAGES NORMAL No symptoms Normal exercise Normal LV fxn Asymptomatic LV Dysfunction Compensated CHF No symptoms Normal exercise Abnormal LV fxn Decompensated CHF No symptoms Exercise Abnormal LV fxn Symptoms Exercise Abnormal LV fxn Refractory CHF Symptoms not controlled with treatment

  5. - Synergistic LV contraction - LV wall integrity - Valvular competence DETERMINANTS OF VENTRICULAR FUNCTION CONTRACTILITY PRELOAD AFTERLOAD STROKE VOLUME HEART RATE CARDIAC OUTPUT

  6. TREATMENT OBJECTIVES Survival Morbidity Exercise capacity Quality of life Neurohormonal changes Progression of CHF Symptoms

  7. Pregnancy Arrhythmias (AF) Infections Hyperthyroidism Thromboembolism Endocarditis Obesity Hypertension Physical activity Dietary excess TREATMENT Correction of aggravating factors MEDICATIONS

  8. TREATMENT PHARMACOLOGIC THERAPY DIURETICS INOTROPES VASODILATORS NEUROHORMONAL ANTAGONISTS OTHERS (Anticoagulants, antiarrhythmics, etc)

  9. DRUGS HEMODYNAMIC EFFECTS Normal A I Stroke Volume A + V V CHF D Ventricular Filling Pressure

  10. PHARMACOLOGIC THERAPY Neurohumoral Control Improved symptoms Decreasedmortality Prevention of CHF yes ? DIURETICS NO ? yes = yes DIGOXIN minimal yes mort. no INOTROPES ? yes yes no Vasodil.(Nitrates) ? yes ACEI YES yes YES Other neurohormonal control drugs + / - yes YES ?

  11. TREATMENT Normal AsymptomaticLV dysfunction EF <40% Symptomatic CHF NYHA II ACEI Symptomatic CHF NYHA - III Diuretics mild Neurohormonal inhibitors Digoxin? Symptomatic CHF NYHA - IV Loop Diuretics Inotropes Specialized therapy Transplant Secondary prevention Modification of physical activity

  12. DIURETICS Thiazides Inhibit active exchange of Cl-Na in the cortical diluting segment of the ascending loop of Henle Cortex K-sparing Inhibit reabsorption of Na in the distal convoluted and collecting tubule Loop diuretics Inhibit exchange of Cl-Na-K in the thick segment of the ascending loop of Henle Medulla Loop of Henle Collecting tubule

  13. THIAZIDESMECHANISM 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. LOOP DIURETICSMECHANISM 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. 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 K-SPARING DIURETICSMECHANISM OF ACTION

  16. DIURETIC 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. DIURETICSADVERSE REACTIONSThiazide 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. DIURETICSADVERSE REACTIONS Thiazide and Loop Diuretics • Idiosyncratic effects: • Blood dyscrasia, cholestatic jaundice and acute pancreatitis • Gastrointestinal effects • Genitourinary effects: • Impotence and menstrual cramps • Deafness, nephrotoxicity • (Loop diuretics)

  19. DIURETICSADVERSE REACTIONS K-SPARING DIURETICS • Changes in electrolytes: • Na+, K+, acidosis • Musculoskeletal: • Cramps, weakness • Cutaneous allergic reactions : • Rash, pruritis

  20. DIGOXIN Na-K ATPase Na-Ca Exchange Na+ K+ Na+ Ca++ Ca++ Myofilaments K+ Na+ CONTRACTILITY

  21. DIGOXINPHARMACOKINETICPROPERTIES • Oral absorption (%) • Protein binding (%) • Volume of distribution (l/Kg) • Half life • Elimination • Onset (min) • i.v. • oral • Maximal effect (h) • i.v. • oral • Duration • Therapeutic level (ng/ml) 60 - 75 25 6 (3-9) 36 (26-46) h Renal 5 - 30 30 - 90 2 - 4 3 - 6 2 - 6 days 0.5 - 2

  22. DIGOXINDIGITALIZATION STRATEGIES Maintenance Dose Loading dose (mg) (mg) 0.125-0.5 / d 0.25 / d i.v 0.5 + 0.25 / 4 h ILD: 0.75-1 oral 12-24 h 0.75 + 0.25 / 6 h 1.25-1.5 oral 2-5 d 0.25 / 6-12 h 1.5-1.75 ILD = average INITIAL dose required for digoxin loading

  23. DIGOXINHEMODYNAMIC EFFECTS Cardiac output LVejection fraction LVEDP Exercisetolerance Natriuresis Neurohormonalactivation

  24. DIGOXINNEUROHORMONALEFFECTS PlasmaNoradrenaline Peripheral nervous system activity RAAS activity Vagaltone Normalizes arterial baroreceptors

  25. DIGOXIN EFFECT ON CHF PROGRESSION 30 Placebo n=93 DIGOXIN Withdrawal % WORSENING OF CHF 20 p = 0.001 DIGOXIN: 0.125 - 0.5 mg /d (0.7 - 2.0 ng/ml) EF < 35% Class I-III (digoxin+diuretic+ACEI) Also significantly decreased exercise time and LVEF. 10 DIGOXIN n=85 0 60 0 20 40 80 100 RADIANCE N Engl J Med 1993;329:1 Days

  26. 50 40 30 20 10 0 OVERALL MORTALITY Placebo n=3403 % p = 0.8 DIGOXIN n=3397 0 12 24 36 48 DIG N Engl J Med 1997;336:525 Months

  27. DIGOXIN LONG TERM EFFECTS Survival similar to placebo Fewer hospital admissions More serious arrhythmias More myocardial infarctions

  28. DIGOXINCLINICALUSES AF with rapid ventricular response CHF refractory to other drugs Other indications? Can be combined with other drugs

  29. DIGOXINCONTRAINDICATIONS ABSOLUTE: - Digoxin toxicity RELATIVE - Advanced A-V block without pacemaker - Bradycardia or sick sinus without PM - PVC’s and TV - Markedhypokalemia - W-P-W with atrial fibrillation

  30. DIGOXIN TOXICITYCARDIAC MANIFESTATIONS ARRHYTHMIAS : - Ventricular (PVCs, TV, VF) - Supraventricular (PACs, SVT) BLOCKS: - S-A and A-V blocks CHF EXACERBATION

  31. DIGOXIN TOXICITYEXTRACARDIACMANIFESTATIONS GASTROINTESTINAL: -Nausea, vomiting, diarrhea NERVOUS: - Depression, disorientation, paresthesias VISUAL: -Blurred vision, scotomas and yellow-green visionHYPERESTROGENISM: - Gynecomastia, galactorrhea

  32. POSITIVE INOTROPES • CARDIAC GLYCOSIDES • SYMPATHOMIMETICS • Catecholamines • ß-adrenergic agonists • PHOSPHODIESTERASE INHIBITORS • Amrinone • Enoximone • Others Milrinone Piroximone

  33. B2 Stimulants Produce arterial vasodilatation and reduce SVR Tretoquinol Salbutamol Soterenol Quinterenol Pirbuterol Carbuterol Rimiterol Fenoterol Terbutaline Salmefamol ß-ADRENERGIC STIMULANTS CLASSIFICATION B1 Stimulants Increase contractility Dobutamine Doxaminol Xamoterol Butopamine Prenalterol Tazolol Mixed Dopamine

  34. DOPAMINE AND DOBUTAMINEEFFECTS DA (µg / Kg / min) Dobutamine < 2 2 - 5 > 5 Receptors DA1 / DA2 ß1 ß1 + a ß1 Contractility ± ++ ++ ++ Heart Rate ± + ++ ± Arterial Press. ± + ++ ++ Renal perfusion ++ + ± + Arrhythmia - ± ++ ±

  35. POSITIVE INOTROPESCONCLUSIONS May increase mortality Safer in lower doses Use only in refractory CHF NOT for use as chronic therapy

  36. VASODILATOR DRUGSPRINCIPLES Normal Contractility Normal Contractility CO VV AV Diminished Contractility Diminished Contractility PRELOAD AFTERLOAD

  37. VASODILATORS CLASSIFICATION Venous Vasodilatation VENOUS Nitrates Molsidomine MIXED Calcium antagonistsa-adrenergic Blockers ACEI Angiotensin II inhibitors K+ channel activators Nitroprusside ARTERIAL Minoxidil Hydralazine Arterial Vasodilatation

  38. • Cardiac output• Blood pressure NITRATESHEMODYNAMIC EFFECTS 1- VENOUS VASODILATATION Preload2- Coronary vasodilatation Myocardialperfusion 3- Arterial vasodilatation Afterload 4- Others Pulmonary congestionVentricular sizeVent. Wall stressMVO2

  39. 400 300 200 100 NITRATESFUNCTIONALCAPACITY n=24 392 384 ** ** EXERCISE TIME, 267 seconds 4 weeks Control 1ST dose ISOSORBIDE 5 - MONONITRATE Jansen W et alMed Welt 1982;33:1756 20 mg / 8h

  40. NITRATESSURVIVAL 0.7 Placebo (273)Prazosin (183)Hz + ISDN (186) 0.6 0.5 PROBABILITYOFDEATH 0.4 0.3 0.2 0.1 0 0 6 12 18 24 30 36 42 VHefT-1 N Engl J Med 1986;314:1547 MONTHS

  41. Develops with all nitrates Is dose-dependent Disappears in 24 h. after stopping the drug Tolerance can be avoided -Using the least effective dose - Creating discontinuous plasma levels NITRATESTOLERANCE " Decrease in the effect of a drug when administered in a long-acting form"

  42. NITRATES TOLERANCE Can be avoided or minimized - Intermittent administration - Use the lowest possible dose - Intersperse a nitrate-free interval Allow peaks and valleys in plasma levels - Vascular smooth muscle recovers its nitrate sensitivity during the nadirs - Patches: remove after 8-10 h

  43. NITRATESTOLERANCE T O L E R A N C E H A L F L I F E s.l. NTG ISDN I 5-MN Percutaneous NTG

  44. NITRATES CONTRAINDICATIONS Previous hypersensitivity Hypotension ( < 80 mmHg) AMI with low ventricular filling pressure 1st trimester of pregnancy WITH CAUTION: • Constrictive pericarditis • Intracranial hypertension • Hypertrophic cardiomyopathy

  45. NITRATESCLINICALUSES Pulmonary congestion Orthopnea and paroxysmal nocturnal dyspnea CHF with myocardial ischemia In acute CHF and pulmonary edema: NTG s.l. or i.v.

  46. ACEI MECHANISM OF ACTION VASOCONSTRICTION VASODILATATION ALDOSTERONE PROSTAGLANDINS VASOPRESSIN tPA Kininogen SYMPATHETIC Kallikrein Angiotensinogen RENIN BRADYKININ Angiotensin I Kininase II A.C.E. Inhibitor ANGIOTENSIN II Inactive Fragments

  47. 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. 4 8 10 14 18 20 2 6 12 ACEIFUNCTIONAL CAPACITY 100 No Additional Treatment Necessary (%) 95 Quinapril continued n=114 90 p<0.001 85 Quinapril stopped Placebo n=110 80 Class II-III 75 16 Quinapril Heart Failure Trial JACC 1993;22:1557 Weeks

  49. ACEIADVANTAGES • Inhibit LV remodeling post-MI • Modify the progression of chronic CHF • - Survival • - Hospitalizations • - Improve the quality of life • In contrast to others vasodilators, do not produce neurohormonal activationor reflex tachycardia • Tolerance to its effects does not develop

  50. ACEI SURVIVAL 0.8 0.7 Placebo 0.6 PROBABILITYOFDEATH p< 0.001 0.5 0.4 p< 0.002 0.3 Enalapril 0.2 0.1 0 CONSENSUS N Engl J Med 1987;316:1429 0 1 2 3 4 5 6 7 8 9 10 11 12 MONTHS

More Related