Pathophysiology of Heart Failure VETM 5291 PDF

Pathophysiology of Heart Failure VETM 5291 Cardiovascular, Respiratory and Hemolymph Systems II Mandy Coleman, DVM, DACVIM (Cardiology) [email protected] Roadmap for the next 3 lectures… Introduce drugs u...

Pathophysiology of Heart Failure VETM 5291 Cardiovascular, Respiratory and Hemolymph Systems II Mandy Coleman, DVM, DACVIM (Cardiology) [email protected] Roadmap for the next 3 lectures… Introduce drugs used in HF treatment Review relevant CV physiology Provide diagnostic criteria for HF Contrast heart Intro basic principles success + failure of HF treatment Describe the patient in HF Review radiographic findings in HF Discuss maladaptive responses to heart DISEASE that lead to heart FAILURE (HF) ▪ Discuss the maladaptive responses to heart disease that ▪ ultimately lead to congestive heart failure (CHF) List and describe the two classic neurohormonal pathways Learning involved in the genesis of CHF Objectives ▪ Diagram the Frank-Starling relationship and use it to describe By the end of this hour, the pathologic alterations to global cardiac function that occur in the setting of heart disease you will be able to… ▪ Explain why animals in acute CHF are almost always presented with sinus tachycardia ▪ Define “forward” and “backward” heart failure and describe clinical manifestations of each ▪ Compare and contrast the physical examination findings of patients with right- vs. left-sided CHF Overview of the cardiovascular system Gas Oxygen Gas Oxygen Oxygen rich exchange poor exchange rich left heart – systemic circulation – right heart – pulmonary circulation – left heart Path of blood flow through heart* HEAD AND FORELIMBS Cranial vena cava 3 4 1 5 2 Caudal vena cava THORAX AND CAUDAL BODY Oxygen-poor blood Oxygen-rich blood Path of blood flow through heart* HEAD AND FORELIMBS 1. Oxygen-poor blood enters right atrium from cranial and caudal vena cavae and coronary sinus Cranial 2. Blood crosses the tricuspid valve to enter the right vena cava ventricle, which pumps it across the pulmonary valve 3 and into the pulmonary circulation through the 4 pulmonary artery 1 3. In the pulmonary capillaries, gas exchange occurs 4. Oxygen-rich blood returns to the left atrium through the 5 pulmonary veins 2 Caudal vena cava 5. Blood crosses the mitral valve to enter the left ventricle, which pumps it across the aortic valve and into the systemic and coronary circulations via the aorta THORAX AND CAUDAL BODY Oxygen-poor blood Oxygen-rich blood  The systemic vascular “tree” Veins deliver blood back to heart and serve as major Arteries distribute blood reservoir for blood under high pressure Venules collect blood from capillaries Small arteries/arterioles: “smooth” arterial pulsations and regulate flow into capillaries (“stopcocks” of the vasculature) Capillaries exchange substances between blood and systemic tissues  Intravascular pressure profiles Systemic Circulation Pulmonary Circulation Values in white call-outs = mean pressures Aortic/arterial pressure is pulsatile Pressures in pulmonary circulation are lower systolic/diastolic = 120/80 Pressure nearly zero when reaches R atrium than in corresponding systemic segments Pressure continues to drop across capillary bed Mean pressure = 17-25 mmHg  RECALL: factors related to myocardial performance Some useful definitions related to cardiac loading: Preload Stretch/tension on relaxed myocytes pre-contraction (at end-diastole) Determined by end-diastolic volume and end- diastolic pressure Afterload Tension on myocardium during systole Resistance that myocardium must overcome to push blood out of the ventricle Muscle “feels” this load after it starts to contract Determined by aortic and systemic vascular resistance RECALL: factors related to myocardial performance Contractility (inotropic state) Intrinsic ability of heart to generate the force required to eject blood, independent of preload and afterload Increased contractility (inotropy) =  velocity and peak force of contraction (heart generates force faster and to a greater final degree)  Heart Failure Defined Heart “Success” Heart Failure ▪ Enough blood is ejected to: ▪ Inability of heart to pump enough blood: ▪ Maintain normal mean arterial pressure ▪ To meet metabolic demands of peripheral Highest priority ▪ Meet body’s metabolic demands tissues (”forward heart failure”) and/or ▪ Adequately drain pulmonary + systemic ▪ To meet these demands without the trade-off veins to maintain appropriate distribution of increased heart filling pressures and poor Lowest of circulating blood pool venous drainage (“backward/congestive priority heart failure”) Heart failure is an end-stage result of severe heart disease, of which there are many causes!! Potential underlying causes of heart failure (Take-home message: there are many!) · · · · · · · · · Table from: Textbook of Veterinary Internal Medicine, 8th ed. Ettinger, Feldman and Cote (eds) 2017  Congestive Heart Failure (CHF) Phase I: initiation Heart ▪ Increased venous/capillary hydrostatic pressure Disease/ upstream of the heart, resulting in tissue edema Injury and/or cavitary effusion) ▪ Maladaptive response to heart disease, mediated by neuro-hormonal changes intended to maintain ↑ Cardiac ↓ Cardiac normal mean arterial pressure (MAP) above all else workload output Vicious cycle of heart failure (↓MAP) (↑MAP) Phase II: compensation Na+ + H2O Neuro- retention, Vasoconstriction hormonal Tachycardia activation Overt RAAS congestion Vasopressin (ADH) Phase III: SNS ET-1 congestion  Congestive Heart Failure (CHF) Phase I: initiation Heart ▪ Increased venous/capillary hydrostatic pressure Disease/ upstream of the heart, resulting in tissue edema Injury and/or cavitary effusion) ▪ Maladaptive response to heart disease, mediated by neuro-hormonal changes intended to maintain ↑ Cardiac ↓ Cardiac normal mean arterial pressure (MAP) above all else: workload output ▪ Sympathetic nervous system (SNS) activation Vicious cycle of ▪ Renin-Angiotensin-Aldosterone System (RAAS) heart failure activation (↓MAP) ▪ Overexpression of endothelin, vasopressin (ADH) (↑MAP) and pro-inflammatory cytokines Phase II: compensation Na+ + H2O Neuro- retention, Vasoconstriction hormonal Tachycardia activation Overt RAAS congestion Vasopressin (ADH) Phase III: SNS ET-1 congestion  Maintenance of normal MAP is priority #1! MAP = ___ x ____ (mean arterial pressure) The cardiovascular system fights to maintain MAP above almost all else!  Maintenance of normal MAP is priority #1! MAP = CO x SVR (mean arterial pressure) (cardiac output) (systemic vascular resistance) (mL/min) The cardiovascular system fights to maintain MAP CO = sum of flows to all tissues of body above almost all else! = volume of blood pumped into aorta per minute  Maintenance of normal MAP is priority #1! ★ MAP = CO x SVR (mean arterial pressure) (cardiac output) (systemic vascular resistance) (mL/min) The cardiovascular system ★ fights to maintain MAP above almost all else! HR x SV (heart rate) (stroke volume) (beats/min) (mL/beat) end-diastolic end-systolic SV = ventricular volume − ventricular volume ★ = Factors manipulated by Determinants of SV: body to return MAP to normal in response to the reduced CO ★ Preload Afterload ★ of heart disease Contractility  Sympathetic Nervous System in early response to heart disease: Heart disease = ↓ cardiac output = ↓ mean arterial pressure (MAP) Baroreceptor Reflex ↓ stretch of arterial baroreceptors = ↓ firing rate Signals to vasomotor center (brain) ↑ sympathetic nervous ↓ parasympathetic system outflow nervous system outflow systemic vasoconstriction (α) ↑ heart rate, contractility ↑ heart rate, contractility (β1) RAAS activation (β1) Baroreceptors These effects located restore MAPin: in the short-term Carotid sinuses (base of internal carotid aa) but are detrimental chronically: they Aortic arch increase the workload on an already- Restoration of normal MAP injured heart and promote further injury! Renin-Angiotensin-Aldosterone System (RAAS) in intermediate- and long-term response to heart disease  Renin-Angiotensin-Aldosterone System (RAAS) in intermediate- and long-term response to heart disease (AT1Receptors) ↑ Thirst and salt hunger CNS effects ↑ ADH (anti-diuretic hormone) release ↑ activity of sympathetic nervous system Myocardial contractility Na+/H20 reabsorption Renal effects Vascular effects Vasoconstriction Stimuli for renin release: Decreased blood pressure (afferent arteriole) Adrenergic stimulation (β1 adrenergic receptors) Decreased Na+ delivery to distal tubule (macula densa)  Renin-Angiotensin-Aldosterone System (RAAS) in intermediate- and long-term response to heart disease Net effects: Thirst and salt hunger ↑preload ADH (anti-diuretic hormone) release activity of sympathetic nervous system ↑HR Myocardial contractility ↑contractility Na+/H20 reabsorption ↑SVR Vasoconstriction MAP = CO x SVR These effects restore MAP in the short-term but are detrimental chronically: they increase the workload on an already-injured heart and promote further injury!  Congestive Heart Failure (CHF) Frank-Starling Relationship ▪ ↑ preload = ↑ stroke volume = ↑ cardiac output (normal Frank-Starling relationship) heart failure Stroke volume/cardiac output ▪ Diseased heart can’t maintain output at “normal” preload + can’t respond fully to preload increases Normal heart ▪ Frank-Starling relationship shifts downward and flattens ▪ Body tries to normalize cardiac output by ↑ preload via a normal tissue perfusion neurohormonal (SNS and RAAS) activation d ▪ Blood volume may be 30% > normal! ⋅ c ⋅ Heart disease Hypotension/ b ▪ Initial cardiac response = eccentric hypertrophy ”forward” ▪ Eventually, excess preload = ↑ diastolic (filling) pressure Venous congestion = ↑ venous + capillary hydrostatic pressures (congestion) (“backward” heart failure) ▪ If venous pressure > 20-25 mmHg (normal, 5-15 mmHg): Left ventricular end-diastolic volume/pressure (PRELOAD) ▪ fluid leak from capillaries > lymphatic drainage ▪ edema/cavitary effusions occur a = normal “operating point” b = operating point in diseased heart at normal preload c = compensated (early) heart disease d = congestive heart failure Cardiogenic pulmonary interstitial edema (Left-sided CHF) Normal microvascular fluid exchange in lung: ▪ Small amount of fluid moves from capillary to interstitum ▪ Fluid removed by lymphatics and returned to circulation ▪ No fluid enters alveoli due to tight cell junctions from: N Engl J Med 2005;353:2788-96 Recall: Starling Forces! Cardiogenic pulmonary interstitial edema (Left-sided CHF) Fluid exchange in chronic left-sided heart disease: ▪ ↑ left-sided filling pressures transmitted to pulmonary veins Alveolus = ↑ pulmonary capillary hydrostatic pressure ▪ If fluid movement out of capillaries > fluid drainage by pulmonary lymphatics, CHF occurs ▪ When left atrial pressure = 20-25 mmHg, interstitial fluid (edema) accumulates ▪ At LAP > 25 mmHg, fluid floods alveoli Capillary from: N Engl J Med 2005;353:2788-96 Recall: Starling Forces!  CO = HR x SV (cardiac output) (heart rate) (stroke volume) (mL/min) (beats/min) (mL/beat) The harm of increased afterload SV influenced by: in heart disease and failure Preload Afterload Contractility  Frank-Starling mechanism also explains how the heart adjusts to acute changes in afterload  For practical purposes, increases in afterload do not substantially reduce stroke volume and cardiac output unless:  Afterload is severely increased  The heart is diseased  Time Compensated heart disease Cardiogenic pulmonary edema due to left- sided congestive heart failure Clinical Manifestations of Heart Failure Heart failure "Forward" (output) failure "Backward" (congestive) failure Right-sided (systemic) Left-sided (pulmonary) congestion congestion  Clinical Manifestations of Heart Failure Consequences of inadequate output Consequences of congestion “Forward” failure “Backward” failure ▪ Generalized weakness, depressed mentation ▪ Abnormal fluid accumulation ▪ ↓ exercise tolerance (esp. performance animals) ▪ If left-sided: interstitial pulmonary edema ▪ Syncope (fainting) ▪ If right-sided: pleural and/or abdominal effusions, peripheral tissue edema ▪ Hypotension, hypothermia ▪ In cats, left-sided CHF may also lead to ▪ Lactic acidosis, azotemia, oliguria due to pleural effusion inadequate tissue perfusion Most patients have a combination of these  Congestive (“backward”) heart failure (CHF) If RIGHT-sided… If LEFT-sided… ▪ Usually: abnormal cardiac exam (e.g., ▪ Usually: abnormal cardiac exam (e.g., murmur, gallop, arrhythmia) murmur, gallop, arrhythmia) ▪ Tachycardia (exception: hypothermic cats) ▪ Tachycardia (exception: hypothermic cats) left atrium right atrium Why do patients with CHF almost always have sinus tachycardia?  Congestive (“backward”) heart failure (CHF) If RIGHT-sided… ▪ Visual evidence of high right-sided filling pressures: ▪ Jugular venous distension/pulsation ▪ Hepatojugular reflux (dogs) ▪ Signs of abnormal fluid accumulation: ▪ Abdominal distension from liver enlargement and/or ascites right ▪ Decreased/absent lung sounds from atrium pleural effusion ▪ Dependent peripheral edema (rare in dogs and cats; common in horses and cattle) Congestive (“backward”) heart failure (CHF) If LEFT-sided… ▪ Respiratory signs due to pulmonary edema: ▪ Dyspnea, tachypnea, orthopnea ▪ Cough (exception: cats) ▪ Expectoration of frothy fluid or frothy left blood-tinged fluid in nostrils (horses) atrium ▪ Fine inspiratory pulmonary “crackles” ▪ Cats only: may have decreased/absent lung sounds due to pleural effusion ▪ Discuss the maladaptive responses to heart disease that ▪ ultimately lead to congestive heart failure (CHF) List and describe the two classic neurohormonal pathways Learning involved in the genesis of CHF Objectives ▪ Diagram the Frank-Starling relationship and use it to describe By the end of this hour, the pathologic alterations to global cardiac function that occur in the setting of heart disease you will be able to… ▪ Explain why animals in acute CHF are almost always presented with sinus tachycardia ▪ Define “forward” and “backward” heart failure and describe clinical manifestations of each ▪ Compare and contrast the physical examination findings of patients with right- vs. left-sided CHF