1 / 88

SCOMPENSO CARDIACO

SCOMPENSO CARDIACO. Incidenza. 4.8 milioni negli USA 400,000 nuovi casi/anno 20 milioni di pazienti con disfunzione asintomatica del VS. Incidenza. 6-10% dei pazienti > 65 anni. #1 causa di ammissione ospedaliera oltre i 65 anni. Spesa annuale di 20-40 miliardi di € per anno. . Mortalità.

anka
Download Presentation

SCOMPENSO CARDIACO

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. SCOMPENSO CARDIACO

  2. Incidenza • 4.8 milioni negli USA • 400,000 nuovi casi/anno • 20 milioni di pazienti con disfunzione asintomatica del VS

  3. Incidenza • 6-10% dei pazienti > 65 anni. • #1 causa di ammissione ospedaliera oltre i 65 anni. • Spesa annuale di 20-40 miliardi di € per anno.

  4. Mortalità • 250,000/anno pazienti muoiono come risultato diretto dello SC. • 1-year mortality rate = 10% • 5-year mortality = 50%

  5. Cause di aumentata incidenza • Miglioramento in: • Sopravvivenza post-IM • Nuove tecnologie (i.e.. Laser, stents etc.) • Trattamento farmacologico • Condizioni generali di vita

  6. Etiology of Chronic Heart Failure • Coronary artery disease accounts for about 65% • Non-ischemic Cardiomyopathy: • Idiopathic • Hypertension • Valvular Heart Disease • Thyroid • Toxic or drug-induced

  7. Etiology of Acute Heart Failure • Myocardial ischemia-infarction • Ventricular systolic or diastolic dysfunction • Mitral valve regurgitation • Ventricular rupture • Myocarditis • Other PE, arrhythmia's, pulmonary HTN

  8. Myocardial Infarction Hypertension Cardiomyopathy Mechanical Strain and pressure Mutations in sarcomeric pressure Ischemia Renin-angiotensin -aldosterone system Sympathetic nervous system Cytokines Growth Factors Free Radicals

  9. Remodeling Process • Hypertrophy • Extracellular Matrix: degradation of collagen and increase in collagen • Re-expression of fetal protein • Changes in myocyte function • Apoptosis • Ejection Fraction • Exercise Tolerance Mitral Regurgitation Arrhythmia • Wall thinning and • ventricular enlargement • Wall stress and O2 consumption

  10. Disease Progression Symptoms Morbidity Death

  11. Pathophysiology of Heart Failure: Left Ventricular Remodeling Left-ventricular (LV) remodeling is defined as a change in LV geometry, mass and volume that occurs over a period of time

  12. Mechanisms Mediating Heart Failure Symptoms • Weak relationship between cardiac performance (EF) and symptoms • Discordance may be due to diastolic dysfunction or valvular heart disease • Also: pulmonary dynamics, neurohormonal activity, peripheral vascular function or skeletal muscle physiology

  13. Mechanisms Mediating Progression • Usually progressive in the absence of identifiable or correctable cause (surgery for valvular heart disease) • Manifestation of progression: • Dilatation • Hypertrophy • geometric change (more spherical) • Promote cardiac remodeling

  14. Pathophysiology and Therapeutic Approaches to Heart Failure • LV Function Digoxin Vasodialtors ACE Inhibitors • Cardiac Output • Peripheral vasoconstriction • Blood flow Neurohormonal Activation • ACE Inhibitors • Blockers Salt and Water Retention Diuretics

  15. Vicious Cycle of Heart Failure Diminished renal blood flow Myocardial dysfunction Diminished Cardiac output Increased cardiac workload Increased Sympathetic Activity Increased force and rate of myocardial contraction Renin release Vasoconstriction Increased venous return Renal retention of sodium and water Angiotensin II Aldosterone Edema

  16. Heart Heart rate Contractility Stroke volume Cardiac output Conduction velocity Myocardial oxygen consumption Peripheral Circulation Arterial vasoconstriction Venoconstriction Systemic vascular resistance Redistribution of blood flow Renal vasoconstriction Effects of Neurohormonal Stimulation in Heart Failure

  17. Ventricular Remodeling: Compensatory Mechanism Dilation Hypertrophy • Globular shape Short term: Compensatory Long term: Harmful

  18. Common Symptoms of Heart Failure Dyspnea on exertion Paroxysmal nocturnal dyspnea Orthopnea Fatigue Lower extremity edema Cough, usually worse at night Nausea, vomiting, anorexia, RUQ pain, ascites Nocturia Sleep disorders Increased abdominal girth

  19. Marked symptoms Pulmonary edema Peripheral edema rare Weight gain none to mild Whole body fluid volume unchanged Wall stress elevated Ventricular systolic function hypo, normal or hyper Marked activation of SNS Increased RAS Acute Heart Failure

  20. New York Heart Association Functional Classification I. No limitation of physical activity, no symptoms with ordinary activities II. Slight limitation, symptoms with ordinary activities III. Marked limitation, symptoms with less than ordinary activities IV. Severe limitation, symptoms of heart failure at rest

  21. Common Physical Findings of Heart Failure Elevated jugular venous pressure Hepatojugular reflux Displaced apical impulse S3 gallop Pulmonary rales Hepatomegaly Peripheral edema Ascites Signs of cardiac cachexia

  22. Increased SVR Total body water increased 16% Plasma volume increased 34% Total body sodium increased 37% Renal blood flow & GFR were reduced Norepinephrine increased 6X normal Renin activity was 9X normal Aldosterone was 6X normal Plasma ANP was 15X normal CHF Patients Prior To Treatment

  23. Spironolactone Angiotensin I Angiotensin II Aldosterone Hypertrophy Apoptosis

  24. Aldosterone • Causes perivascular and interstitial cardiac fibrosis • systolic & diastolic dysfunction • May generate reentrant arrhythmia's • Inhibits reuptake of norepinephrine • Impairs baro-reflex mediated heart rate variability • Augments sympathetic activity

  25. Aldosterone Cont . . . • Inhibits parasympathetic flow • Impairs arterial compliance • Promotes potassium and magnesium depletion

  26. Aldosterone Antagonists • Potassium-sparing diuretics • Compete with aldosterone for receptor sites in the distal renal tubules • Increase sodium and water excretion while conserving potassium and hydrogen ions

  27. Rales Trial • 1663 patients with recent or current Class IV heart failure (already on ACE I ) were randomized to placebo or spironolactone for mean 24 months • Spironolactone reduced all-cause mortality by 27%, hospitalizations for heart failure by 36% and combined risk of death or hospitalization for any reason by 22% NEJM 1999; 341:709-717

  28. Aldosterone Antagonist • HFSA Consensus Guidelines: • Use in Class IV heart failure • Should be given low dose (12.5mg - 25mg daily)

  29. Aldosterone Antagonists: Adverse Effects • Arrhythmia, nervousness, dizziness, fatigue, rash, headache, breast tenderness, enlargement of breast in males, sexual dysfunction, increased hair growth in females, GI irritation • May decrease effects of anticoagulants • Use with caution in renal insufficieny

  30. ACE-Inhibitors Angiotensin I Angiotensin II Aldosterone Hypertrophy Apoptosis Spironolactone

  31. Management: Angiotensin-Converting Enzyme Inhibitors • ACE inhibitors suppress conversion of angiotensin I to angiotensin II • Benefits of ACE inhibitors • Reduce cardiac hypertrophy • Attenuate ventricular remodeling post MI • Cause peripheral vasodilation • Decrease sympathetic tone • Enhance activity of kinin

  32. Angiotensin Receptor Blockers • Block the angiotensin II receptor • Elite II Trial • 3152 elderly patients with heart failure randomized to captopril or losartan for 3 years. When compared with losartan the captopril group had: • 12% lower risk of death • 20%lower risk of lethal arrhythmia Lancet 1997:349: 747-752

  33. Angiotensin II Norepinephrine Hypertrophy, apoptosis, ischemia, arrhythmia's, remodeling, fibrosis

  34. Effect of Sympathetic Activation in Heart Failure • CNS Sympathetic Outflow • Sympathetic activity to kidneys & blood vessels • Cardiac sympathetic Activity • 1 Receptors • 1 Receptors • 2 Receptors Activation of RAS Myocyte death Increased arrhythmias Vasoconstriction Sodium retention Disease Progression

  35. Management: Beta Blockers • Beta receptor levels in heart failure • Normal Heart B1 80 : B2 20 • Severe Heart Failure B1 60 : B2 40 • B1 receptors to selectively down-regulate secondary to high levels of catecholamine • B2 agonists retain full inotropic activity mediated through a B2 population that is not significantly decreased

  36. Pharmacologic Classes of Beta-Adrenergic Receptor Blockers • First Generation Agents • Non-selective agents without desirable ancillary properties • Propanolol, timolol • Second Generation Agents • Selective B1 agents without desirable properties • Metoprolol, Bisoprolol • Third Generation Agents • Non-selective with benefical cardiovascular properties • Carvedilol

  37. Effect of ACE inhibitors On Mortality • Captopril-Digoxin Multicenter Trial • 300 patients with a ischemic and nonischemic cardiomyopathy, class II-III, were randomized to digoxin or captopril • Captopril improved exercise tolerance • Decreased need for more diuretic • Decreased occurrence of worsening heart failure JAMA 1988; 259:539-544

  38. More ACE Trials • Studies of left ventricular dysfunction (SOLVD) • 2569 patients with primarily class II-III CHF were randomized to placebo or enalapril for over 48 months • 16% reduction in all-cause mortality • 26% decrease in the risk of death or hospitalization for heart failure NEJM 1991;325:293-302

  39. Clinical Trial Data - Summary • Available trials of ACE inhibitor clearly demonstrate that these agents reduce mortality & morbidity in patients with compromised LV function • Benefits extend to different patient groups

  40. HFSA Consensus Recommendations ACE Inhibitors • All patients with heart failure due to left ventricular systolic dysfunction should receive an ACE inhibitor unless they have a contraindication to its use or cannot tolerate treatment with the drug. Treatment with an ACE inhibitor should not be delayed until the patient is found to be resistant to treatment with other drugs.

  41. Clinical Use Of ACE Inhibitors • Recommended for all patients with CHF and systolic dysfunction • Recommended for patients with systolic dysfunction and no symptoms of CHF • Prevents CHF in patients with preserved LV (EF > 40%) and CAD or risk factors (HOPE Trial)

  42. Clinical Use Cont . . . • Initiation of ACE inhibitor - Therapy should be initiated with low doses to avoid excessive hypotension • Target doses - Doses should be slowly titrated to achieve targeted dose used in major clinical trials

  43. ACE Inhibitors: Adverse Effects • Severe hypotension, syncope, renal insufficiency, hyperkalemia and angioedema • Some adverse effects can be avoided by initiating and titrating by low doses. Need to monitor BP, lytes and renal function • Most frequent side effect is cough (5-15%) - cross sensitivity likely

  44. ACE Inhibitors Cont . . . • Contraindications • Allergic reaction • Pregnancy • Very low BP (<80mmHg) • Creatinine > 3 • Bilateral renal artery stenosis • Potassium > 5.5

  45. HFSA Recommendations: Angiotensin Receptor Blockers • Angiotensin II receptor blockers should not be used for the treatment of heart failure in patients with no prior use of ACE inhibitors and should not be substituted for ACE inhibitors in patients who are tolerating ACE inhibitors without difficulty

  46. Beta Blocker Evidence • Initially contraindicated in heart failure due to negative inotropy, early lack of tolerability and worsening heart failure • Over 10,000 patients have now been evaluated in long-term, placebo-controlled clinical trials • Effects shown in patients already receiving ACE inhibitors

  47. Clinical Trials • Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise (PRECISE) • 278 patients with chronic stable symptomatic heart failure EF<35% despite diuretics and ACE • Carvedilol group was associated with greater improvement in NYHA Class • 39% reduction in combined risk of death/hospitalization for any reason • 46% reduction in risk of hospitalization for cardiovascular reason Circulation 1996;94:2793-2799

  48. Clinical Trials • Merit-HF Trial • 3991 patients with an ischemic or nonischemic cardiomyopathy (NYHA Class II or III) randomized to either Metoprolol XL up to 200mg/day or placebo. • Metoprolol XL was associated with a 35% reduction in mortality • DSMB recommended early termination of the study Amer J Cardiol 1997;80:54J-58J

More Related