Outline. Pathophysiology: Heart Failure. Heart Failure. Heart Failure: Definitions. Etiologies. Etiologies

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1 Outline Pathophysiology: Mat Maurer, MD Irving Assistant Professor of Medicine Definitions and Classifications Epidemiology Muscle and Chamber Function Pathophysiology : Definitions An inability of the heart to pump blood at a sufficient rate to meet the metabolic demands of the body (e.g. oxygen and cell nutrients) at rest and during effort or to do so only if the cardiac filling pressures are abnormally high. A complex clinical syndrome characterized by abnormalities in cardiac function and neurohormonal regulation, which are accompanied by effort intolerance, fluid retention and a reduced longevity A complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Not a disease A syndrome From "syn meaning "together and "dromos" meaning "a running. A group of signs and symptoms that occur together and characterize a particular abnormality. Diverse etiologies Several mechanisms Ischemia Hypertrophy Arterial Stiffness Atrial Fibrillation Diabetes Infiltrative Disease Hypertension CAD Valvular Disease Pericardial Disease Ischemic cardiomyopathy Valvular cardiomyopathy Hypertensive cardiomyopathy. Inflammatory cardiomyopathy Metabolic cardiomyopathy General system disease Muscular dystrophies. Neuromuscular disorders. Sensitivity and toxic reactions. Peripartal cardiomyopathy Circulation. 1996;93:

2 : Classifications Paradigms Restrcitive Patients in the US (Millions) Epidemiology : The Problem million in 1991, 4.7 million in 2000, estimated million in 2037 Incidence: 550,000 new cases/year Prevalence: 1% ages , >% over age 80 More deaths from HF than from all forms of cancer combined Most common cause for hospitalization in age >65 Tension (g) Preload Muscle Length (mm) The length of a cardiac muscle fiber prior to the onset of contraction. Frank Starling b a Cardiac Muscle Function d c Tension (g) Afterload e L c L a a c Muscle Length (mm) The against which a cardiac muscle fiber must shorten. Isotonic Contraction Tension (g) Contractility +norepinephrine f b g e a Muscle Length (mm) The force of contraction independent of preload and afterload. Inotropic State From Muscle to Chamber The Pressure Volume Loop Diastole Systole

3 The Pressure Volume Loop Compliance/Stiffness vs Capacitance P es 25 EDPVR Pressure ESPVR Preload Volume EDPVR LV Pressure (mmhg) Capacitance = volume at specified pressure Slope = stiffness = 1/compliance LV Volume (ml) LV Pressure (mmhg) 50 Diastolic Dysfunciton LV Volume (ml) Cardiac Chamber Function Preload Afterload Contractility Frank Starling Curves Hypotension Pulmonary Congestion EDV EDP Wall stress at end diastole Aortic Pressure Total peripheral resistance Arterial impedance Wall stress Pressure generated at given volume. Inotropic State Pathophysiology - PV Loop Pathophyisiology of myocardial remodeling: Transition from compensated hypertrophy to heart failure Insult / Stimuli Wall Stress Cytokines Neurohormones Oxidative stress Increased Wall Stress Myocyte Hypertrophy Altered interstitial matrix Fetal Gene Expression Altered calcium handling proteins Myocyte Death Ventricular Enlargement Diastolic Systolic

4 Ventricular Laplace s Law Where P = ventricular pressure, r = ventricular chamber radius and h = ventricular wall thickness Neurohormonal Activation in Neurohormones in Myocardial injury to the heart (CAD, HTN, CMP, valvular disease) Initial fall in LV performance, wall stress Activation of RAS and SNS Myocardial Injury Activation of RAAS and SNS (endothelin, AVP, cytokines) Fall in LV Performance and progressive worsening of LV function Morbidity and mortality Arrhythmias Pump failure RAS, renin-angiotensin system; SNS, sympathetic nervous system. Fibrosis, apoptosis, hypertrophy, cellular/molecular alterations, myotoxicity Peripheral vasoconstriction Sodium retention Hemodynamic alterations Heart failure symptoms Fatigue Activity altered Chest congestion Edema Shortness of breath Myocardial Toxicity Change in Gene Expression Morbidity and Mortality Shah M et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2 ANP BNP and Progressive Worsening of LV Function Peripheral Sodium/Water Retention HF Symptoms Neurohormonal Activation in Angiotensin II Norepinephrine Adrenergic Pathway in Heart Failure Progression CNS sympathetic outflow Vascular sympathetic activity Cardiac sympathetic activity Renal sympathetic activity β 1 β 2 α 1 α 1 β 1 α 1 Hypertrophy, apoptosis, ischemia, arrhythmias, remodeling, fibrosis Myocyte hypertrophy Myocyte injury Increased arrhythmias Activation of RAS Sodium retention Morbidity and Mortality Disease progression

5 Pathophysiology of Four Basic Mechanisms 1. Increased Blood Volume (Excessive Preload) 2. Increased Resistant to Blood Flow (Excessive Afterload) 3. Decreased contractility 4. Decreased Filling Aortic Regurgitation Mitral Regurgitation Aortic Regurgitation Volume Overload Left to Right Shunts Chronic Kidney Disease Increased Blood Volume Ventricular Parameter BP (mm Hg) SV (ml) AI + Cardiac (L/min) PCWP (mm Hg) Na Retention AI 140/75/99 128/ AI + HF AI + 85/35/ AI + Heart failure 4/45/ Hypertension Increased Afterload HTN + DD HTN + DD + HF Decreased Contractility MI MI + MI + Diastolic Na Retention Ventricular Na Retention Aortic Stenosis Aortic Coarctation Hypertension Parameter BP (mm Hg) SV (ml) Cardiac (L/min) PCWP (mm Hg) 124/ HTN 159/ HTN + DD 170/ HTN + Heart failure 206/ Ischemic Cardiomyopathy Myocardial Infarction Myocardial Ischemia Myocarditis Toxins Anthracycline Alcohol Cocaine Parameter BP (mm Hg) SV (ml) Cardiac (L/min) PCWP (mm Hg) 124/ MI 68/ MI + 68/ MI + HF 80/ Decreased Filling HCM HCM + HF Ventricular Na Retention : Classifications Parameter HCM HCM + Mitral Stenosis HF Constriction Restrictive Cardiomypoathy BP (mm Hg) 124/81 112/74 131/87 Cardiac Tamponade SV (ml) Hypertrophic Cardiomyopathy Cardiac (L/min) Infiltrative Cardiomyopathy PCWP (mm Hg) 27 Restrcitive

6 Types of Systolic Versus Diastolic Failure SHF Diastolic Systolic Diastolic Contractility Pathophysiology Impaired Contraction Impaired filling Pressure Pressure Pressure Capacitance Demographics All ages > 60 years 1 Cause Coronary Artery Disease Hypertension Volume Volume Volume Systolic Versus Diastolic Failure : Classifications Restrcitive : Classifications Restrictive

7 Failure : Classifications Causes: Anemia Systemic arteriovenous fistulas Hyperthyroidism Beriberi heart disease Paget disease of bone Glomerulonephritis Polycythemia vera Carcinoid syndrome Obesity Restrictive Restrictive Restrictive Type Dilated Hypertrophic Restrictive Definition Dilated left/both ventricle(s) with impaired contraction Left and/or right ventricular hypertrophy Restrictive filling and reduced diastolic filling of one/both ventricles, /near normal systolic function Sample Ischemic, idiopathic, familial, viral, alcoholic, toxic, valvular Familial with autosomal dominant inheritance Idiopathic, amyloidosis, endomyocardial fibrosis Clinical Manifestations Symptoms Reduced exercise tolerance Shortness of breath Congestion Fluid retention Difficulty in sleeping Weight loss Diagnosis of heart failure Physical examination Chest X ray EKG Echocardiogram Blood tests: Na, BUN, Creatinine, BNP Exercise test MRI Cardiac catheterization

8 I II III IV Class Mild Mild Moderate Severe NYHA Classification Patient Symptoms No limitation of physical activity No undue fatigue, palpitation or dyspnea Slight limitation of physical activity Comfortable at rest Less than ordinary activity results in fatigue, palpitation, or dyspnea Marked limitation of physical activity Comfortable at rest Less than ordinary activity results in fatigue, palpitation, or dyspnea Unable to carry out any physical activity without discomfort Symptoms of cardiac insufficiency at rest Physical activity causes increased discomfort ACC/AHA Staging System STAGE A High risk for developing HF STAGE B Asymptomatic LV dysfunction STAGE C Past or current symptoms of HF STAGE D End-stage HF Hunt, et al. J Am Coll Cardiol. 2001; 38: A B C D Stage ACC/AHA Staging System High risk for developing heart failure Asymptomatic heart failure Symptomatic heart failure Refractory end-stage heart failure Patient Description Hypertension Coronary artery disease Diabetes mellitus Family history of cardiomyopathy Previous myocardial infarction Left ventricular systolic dysfunction Asymptomatic valvular disease Known structural heart disease Shortness of breath and fatigue Reduced exercise tolerance Marked symptoms at rest despite maximal medical therapy (e.g., those who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions) Goals of Treatment 1. Identification and correction of underlying condition causing heart failure. 2. Elimination of acute precipitating cause of symptoms. 3. Modulation of neurohormonal response to prevent progression of disease. 4. Improve long term survival. A B C D Stage High risk for developing heart failure Asymptomatic heart failure Symptomatic heart failure Refractory end-stage heart failure Treatment Patient Treatment Hypertension Optimal pharmacologic therapy (OPT) Coronary artery disease Aspirin, ACE inhibitors, statins, b-blockers, a-b-blockers Diabetes mellitus (carvedilol) diabetic therapy Family history of cardiomyopathy OPT Previous myocardial infarction ICD Left if left ventricular systolic (LV) dysfunction (systolic) present Asymptomatic valvular disease OPT Known structural heart disease ICD Shortness if LV dysfunction of breath and (systolic) fatigue present CRT Reduced (if QRS exercise wide, LVEF 35%) tolerance OPT Marked symptoms at rest despite maximal Intermittent medical therapy IV inotropes (e.g., those who are recurrently ICD hospitalized as a bridge or to cannot transplantation be safely discharged from CRT the hospital without specialized interventions) Other devices (LVAD, pericardial restraint) Targets of Treatment Standard Pharmacological Therapy ACE inhibitors Angiotensin Receptor Blockers Beta Blcokers Diuretics Aldosterone Antagonists Statins Vasodilators Inotropes

9 ACC/AHA Staging System Treatment Summary Complex Clinical Syndrome Multiple and Classification Systems Physiologic Understanding Essential

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