Heart Failure
Definition of Congestive Heart Failure A clinical syndrome of signs & symptoms resulting from the heart s inability to supply adequate tissue perfusion.
CHF Epidemiology Affects 4.7 million Americans 500,000 new cases diagnosed annually 6-10% of patients over 65 y.o. 1-year mortality rate = 10% 5-year mortality = 50%
Contributors to Increased Incidence Improvements in: Survival post-mi Technologies (i.e.. Laser, stents etc.) Medical Treatments for ischemic heart disease Overall survival
Etiology of Chronic Heart Failure Coronary artery disease accounts for about 65% Non-ischemic Cardiomyopathy: DM Hypertension Valvular Heart Disease Thyroid Toxic or drug-induced
Pathophysiology and Therapeutic Approaches to Heart Failure Vasodialtors ACE Inhibitors Peripheral vasoconstriction Blood flow LV Function Digoxin Cardiac Output Salt and Water Retention Neurohormonal Activation ACE Inhibitors ß Blockers Diuretics
Steering Committee and Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure. Am J Cardiol. 1999;83(Suppl 2A):1A 38A. Two Systems Two Therapies Angiotensin II (Renin-Angiotensin System [RAS]) Norepinephrine (Sympathetic Nervous System [SNS]) ACE Inhibition -Blockade Disease Progression
Framingham Criteria for the Clinical Diagnosis of CHF Major Criteria PND Orthopnea Elevated JVP Pulmonary rales S3 Cardiomegaly on CXR Pulmonary edema on CXR Minor Criteria Peripheral edema Nocturnal cough DOE Hepatomegaly Pleural Effusion HR >120 Wt loss >4.5 kg in 5 days CHF= 2 Major OR 1 major and 2 minor criteria
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
CHF Patients Prior To Treatment 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
Congestive heart failure Classification Systolic heart failure vs. diastolic heart failure Right heart failure vs. left heart failure Forward heart failure vs. backward heart failure
Systolic Heart Failure Diastolic Heart Failure
Management of Heart Failure Life style ACE inhibitor Beta blocker Diuretics Combined nitrate and vasodilator Pacemaker Digoxin Positive inotropics
Lifestyle Measures Sodium restriction (2G/day) No salt substitutes Daily weight Fluid restriction
Lifestyle Measures Cont... Exercise Avoid heavy lifting Avoid temperature extremes
Lifestyle Measures Cont... Stress management Fluid Restriction
Management of Heart Failure Life style ACE inhibitor, ARB Beta blocker Diuretics Combined nitrate and vasodilator Digoxin Positive inotropics Pacemaker
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)
Management of Heart Failure Life style ACE inhibitor Beta blocker Diuretics Combined nitrate and vasodilator Digoxin Positive inotropics Pacemaker
Angiotensin II Norepinephrine Hypertrophy, apoptosis, ischemia, arrhythmia's, remodeling, fibrosis
Relation between plasma noradrenaline and mortality in patients with heart failure Cumulative mortality (%) 100 80 Overall p<0.0001 Noradrenaline > 900 pg/ml 60 40 20 Noradrenaline > 600 pg/ml and < 900 pg/ml Noradrenaline < 600 pg/ml 0 0 12 24 36 48 60 Months NEJM 1984; 311: 819-823
Receptor Density (fmol/mg Protein) Adrenergic Receptors in Normal vs Failing Human Left Ventricles 80 70 60 1 2 a 1 50 40 30 20 10 * * 0 Normal Function (n=12) 1 : 2 :a 1 = 70%:20%:10% Cardiomyopathy (n=54) 1 : 2 :a 1 = 50%:25%:25% *P<.05 vs normal function. Adapted from Bristow MR. J Am Coll Cardiol. 1993;22:61A 71A. Bristow MR. Am J Cardiol. 1997;80:26L 40L.
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
Are All Beta Blockers Equally Beneficial In Heart Failure? B1 Receptors B2 Receptors A1 Receptors Metoprolol Propranolol Cardiotoxicity Carvedilol
Clinical Use Of Beta Blockers Recommended for patients with NYHA class II-IV General contraindications: Decompensated heart failure Severe claudication Bronchospasm Advanced heart block Use with caution if patient requires inotropes for support of circulatory function