Pathophysiology of Heart Failure Lecture 08 PDF

PATHOPHYSIOLOGY OF HEART FAILURE Lecture 08 Richard Klabunde, PhD Professor of Physiology MU-WCOM 1 Learning objectives 1. Define heart failure and list major causes 2. Differentiate between systolic (HFrEF) and dias...

PATHOPHYSIOLOGY OF HEART FAILURE Lecture 08 Richard Klabunde, PhD Professor of Physiology MU-WCOM 1 Learning objectives 1. Define heart failure and list major causes 2. Differentiate between systolic (HFrEF) and diastolic dysfunction (HFpEF) 3. Explain how systolic dysfunction affects Frank-Starling curves, pressure- volume loops (EDV, ESV, EF), and ventricular compliance 4. Explain how diastolic dysfunction affects ventricular compliance and pressure-volume loops (EDV, ESV, EF) 5. Describe the beneficial and deleterious effects of neurohumoral compensatory responses to heart failure 6. Describe how heart failure impairs the cardiovascular responses to exercise. 2 Learning resources Klabunde, Cardiovascular Physiology Concepts, Wolters Kluwer: 3e (Ch 2: 9-17; Ch 9: 236-243) Guided Learning: Heart Failure at cvphysiology.com Links found on slides 3 Definition of heart failure Inability of the heart to deliver adequate blood flow and oxygen delivery to organs, or to do so only at elevated filling pressures 4 Two major categories of heart failure Heart Failure with Reduced Ejection Fraction (HFrEF) Systolic dysfunction Loss of ability to contract (depressed inotropy) that can lead to decreased forward flow and clinical symptoms of heart failure with reduced EF (≤40%) Heart Failure with Preserved Ejection Fraction (HFpEF) Diastolic dysfunction Impaired ventricular filling with elevated filling pressures that can lead to decreased forward flow and clinical symptoms of heart failure with preserved EF (≥50%) 5 Causes of heart failure HFrEF HFpEF Ischemic heart disease and infarction Ventricular concentric hypertrophy Dilated cardiomyopathies caused by Myocarditis ○ Chronic hypertension Persistent tachycardia ○ Aortic valve stenosis Chronic volume and pressure ○ Genetic defect (hypertrophic cardiomyopathy, HCM) overload ○ Valve disease Restrictive cardiomyopathy ○ Chronic hypertension Cardiac tamponade ○ Congenital cardiac defects Impaired relaxation (e.g., ischemia) ○ Pregnancy 6 Neurohumoral compensation in heart failure Sympathetic nerves and catecholamine release are activated by: Baroreceptor reflex – acute failure Cardiac stretch receptors Chronic, central sympathetic activation Increased circulating angiotensin II (peripheral and central effects) RAAS activated by: Reduced renal perfusion Increased sympathetic activity Enhanced release of vasopressin (stimulated by sympathetic activation and AII) and ANP (stimulated by atrial distension) 7 Summary of neurohumoral responses to heart failure Klabunde, Cardiovascular Physiology Concepts, 3e 8 Sympathetic activation and catecholamine release Acute heart failure Hypotension causes ↓ firing of arterial baroreceptors → reflex sympathetic activation Sympathetic stimulation of adrenal catecholamine release Chronic heart failure Central activation of sympathetic system Stimulated by angiotensin and cardiopulmonary receptors 9 Renin-angiotensin-aldosterone system (RAAS) activation Activated by: Reduce renal perfusion Sympathetic stimulation Causes Renal retention of Na+ and H2O Increased blood volume and venous pressures Vascular constriction (↑SVR) Stimulates vasopressin (ADH) release Enhances sympathetic activity Cardiac remodeling 10 Natriuretic peptides (ANP) Release: Synthesized and released by atria Release is stimulated by Atrial stretch Sympathetic stimulation Angiotensin II (AII) Actions Inhibit RAAS system and thereby promote natriuresis and diuresis Arterial & venous vasodilation Lowers arterial & venous pressures 11 Vasopressin (ADH) release Activated by: Sympathetic stimulation Increased angiotensin II Causes Renal reabsorption of H2O Increased blood volume and venous pressures Arterial constriction (↑SVR) 12 Benefits of neurohumoral activation Increased blood volume (increased preload) helps to maintain stroke volume through the Frank-Starling mechanism Cardiac stimulation and systemic vasoconstriction help to maintain arterial pressure to support perfusion of vital organs Stimulates cardiac remodeling 13 Deleterious effects of neurohumoral activation Increased blood volume increases venous pressures leading to pulmonary and systemic edema Systemic constriction can increase afterload and impair ventricular ejection Stimulates molecular and biochemical changes that promote cardiac dysfunction over time Promotes arrhythmias 14  Heart failure signs and symptoms Sign or Symptom Cause(s) Exertional dyspnea Pulmonary edema impairing gas exchange; chemoreceptor responses Exercise intolerance Impaired oxygen delivery to muscles Cognition deficits and fatigue Impaired brain and peripheral blood flow Cough or wheezing Pulmonary edema caused by left heart failure and increased blood volume Swelling of legs, abdomen Systemic edema caused by right heart failure and increased blood volume Arrhythmias Remodeling of cardiac chambers (stretching, hypertrophy); myocardial ischemia Cardiac murmurs Chamber dilation causing valve regurgitation 15 SYSTOLIC DYSFUNCTION 16 Effects of acute systolic dysfunction on Frank- Starling curves Loss of intrinsic inotropy (min, hrs, days) results in ↓SV and ↓EF at a given ventricular preload Cardiac compensation includes: Ventricular dilation (passive dilation, not remodeling; limited if already dilated by chronic heart failure) ↑EDV & ↑EDP (↑preload → partial SV recovery) ↑HR (sympathetic activation) 17 Effects of acute systolic dysfunction on pressure- volume loops Loss of intrinsic inotropy (↓ESPVR) causes: ↓SV (70 → 45 mL) and ↓EF (58 → 29%) ↓Systolic and diastolic aortic pressures Cardiac compensation includes: Ventricular passive dilation (not remodeling) ↑EDV (120 → 155 mL) ↑ESV > ↑EDV → ↓SV ↑EDP (10 → 25 mmHg); ↓ventricular compliance (steeper EDPVR) at higher volumes ↑HR (sympathetic activation) may contribute to ↓SV ↓Stroke work (area within P-V loop) 18 Acute vs. chronic systolic dysfunction and ventricular compliance Ventricular compliance: Compliance is inversely related to cardiac “stiffness” At a given EDV (vertical dashed line), the EDP is inversely related to compliance Acute dysfunction (green arrow) moves up normal ventricular compliance (ventricular filling) curve; ↑↑EDP (PCWP) Chronic dysfunction leads to ventricular remodeling (red arrow), which increases compliance and EDV; attenuates the increase in EDP www.cvphysiology.com/Cardiac%20Function/CF014.htm 19 Effects of chronic systolic dysfunction on ventricular pressure-volume relationship Loss of intrinsic inotropy results in depressed ESPVR Chronic dilation (remodeling → ↑ compliance; depressed EDPVR) relative to acute Cardiac changes: ↑ESV > ↑EDV → ↓SV (50 mL vs. normal of 70 mL) ↓EF (25% vs. normal of 58%) ↑LVEDP & PCWP, but < acute HFrEF ↓stroke work 20 HFrEF: Cardiopulmonary & systemic changes Reduced SV and EF Increased filling pressures (↑↑ LVEDV, ↑ LVEDP, ↑ LAP and pulmonary pressures, ↑ RVEDP, ↑ RAP) Pulmonary congestion and edema Increased blood volume Systemic edema 21 DIASTOLIC DYSFUNCTION 22 Diastolic dysfunction results from decreased ventricular compliance Reduced ventricular compliance (↑ “stiffness”) Rotates P-V filling curve (EDPVR) to the left At a given EDV (vertical dashed line), ↓ compliance → ↑EDP Diastolic dysfunction increases EDP and generally decreases EDV because filling is impaired (yellow arrow) www.cvphysiology.com/Cardiac%20Function/CF014.htm 23 Effects of diastolic dysfunction on ventricular pressure-volume relationship Diastolic dysfunction reduced ventricular compliance (↑EDPVR slope) Results in: Lower preload volume (↓EDV) with higher preload pressure (↑↑EDP) (yellow arrow) ESV may ↓ because of ↓afterload ↓SV with little or no change in EF; the ratio of SV/EDV does not change much ↓stroke work 24 HFpEF: Cardiopulmonary & systemic changes Reduced SV, but normal EF Increased filling pressures (↓ LVEDV, ↑↑ LVEDP, ↑↑ LAP and pulmonary pressures, ↑ RVEDP, and ↑ RAP) Pulmonary congestion and edema Increased blood volume Systemic edema 25 COMBINED SYSTOLIC AND DIASTOLIC DYSFUNCTION 26 Combined systolic & diastolic dysfunction Decreased ejection (systolic dysfx) ↑ESV and ↓peak systolic pressure Decreased filling (diastolic dysfx) ↓EDV and ↑↑EDP Net effects: ↓↓SV and ↓EF ↑↑EDP (filling pressure) ↓↓stroke work NOTE: Above changes are highly dependent on relative reductions in inotropy and compliance 27  IMPAIRED EXERCISE RESPONSES IN HEART FAILURE 28 Comparison of exercise responses in normal and heart failure patients CO HR SV MAP (liters/min) (beats/min) (mL) (mmHg) Normal 5.6 70 80 95 (Rest) Normal 18.0 170 106 120 (Max) CHF 4.0 80 50 90 (Rest) CHF 6.0 120 50 85 (Max) Klabunde, Cardiovascular Physiology Concepts, 3e 29 CV responses in CHF patients Maximal cardiac output is reduced Maximal heart rate limited by dyspnea and fatigue Normal increases in stroke volume are reduced Impaired inotropic responses (particularly in HFrEF patients) Dyspnea and muscle fatigue limit exercise response Impaired gas exchange caused by pulmonary congestion and edema Impaired pulmonary perfusion coupled to respiratory fatigue (increased work of breathing) Skeletal muscle fatigue caused by insufficient oxygen delivery to the contracting muscles 30 END 31 QUESTIONS 32 Q1: What causes ESV to increase and SV to decrease with systolic dysfunction? A. Decreased afterload B. Increased end-diastolic volume C. Reduced ejection velocity D. Decreased ventricular complianc 33 Q2: Why does reducing afterload with an arterial vasodilator improve left ventricular ejection in systolic dysfunction? A. End-systolic volume is increased B. Frank-Starling mechanism is activated C. Preload is increased D. Velocity of fiber shortening is increased 34 Q3: How does left ventricular diastolic dysfunction cause pulmonary edema? A. Pulmonary blood volume is increased B. Pulmonary capillary oncotic pressure is increased C. Pulmonary capillary hydrostatic pressure is decreased D. Venous return is increased 35 36 Answers to questions Q1: C Loss of inotropy reduces SV because of reduced velocity of fiber shortening and therefore reduced ejection velocity, which leads to an increase in ESV. Q2: D Reducing afterload on the LV increases myocyte shortening velocity (through the force- velocity relationship) and therefore increases ejection velocity, which increases the SV and decreases the ESV. Q3: A Diastolic dysfunction results from reduced anatomic or functional ventricular compliance, which leads to increased filling pressures (increased LVEDP). This is transmitted back into the left atrium and pulmonary veins (increased PCWP), which increases pulmonary blood volume and pressures leading to increased capillary fluid filtration. 37