Notes On Peptic Ulcer

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This note is a vast explanation of a common Gastro intestinal tract disorder ,PEPTIC ULCER. I have included etiology,pathophysiology,histopathology, morphology and complications of peptic ulcer.

Vishnu N / Palakkad

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Qualification: MBBS (Vinayaka Mission University , Salem - 2016)

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Boards&Beyond Boards and Beyond: Cardiology Slides Slides from the Boards and Beyond Website Jason Ryan, MD, MPH 2019 Edition i
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Table of Contents Cardiac Anatomy Cardiac Physiology CV Response to Exercise Blood Flow Mechanics Regulation of Blood Pressure PV Loops Wiggers' Diagram Venous Pressure Tracings Starling Curve Atherosclerosis Cardiac Ischemia STEMI Unstable Angina/NSTEMl Stable angina EKG Basics High Yield EKGs Action Potentials AV and Bundle Branch Blocks Atrial Fibrillation AVNRT WPW Antiarrhythmic Drugs 1 3 8 10 16 20 24 26 28 31 35 42 47 49 55 61 65 69 74 81 83 85 Heart Murmurs Heart Sounds Heart Failure Basics Systolic and Diastolic Heart Failure Restrictive Cardiomyopathy Acute Heart Failure Chronic Heart Failure Cardiac Embryology Shunts Cyanotic Congenital Heart Disease Coarctation of the Aorta Hypertension Secondary Hypertension Hypertension drugs Valve Disease Shock Pericardial Disease Aortic dissection Cardiac Tumors Hypertrophic Cardiomyopathy Endocarditis iii 96 101 105 111 115 118 123 127 131 135 141 145 148 153 161 167 171 177 181 184 188
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The Heart Chambers PVs Cardiac Anatomy Jason Ryan, MD, MPH The Heart Valves PA Aorta LV IVC RV Coronary Arteries Heart drains to coronary sinus CS Right atrium RCA LAD AV MV 90% Right dominant 10% Left dominant Left Main LCX PDA Anterior-Posterior Structures Right Ventricle -5 Anterior Left atrium Posterior Coronary Artery Territories Anterior wall, anterior septum, apex LAD Lateral wall LCX Inferior wall, inferior septum -5 PDA RCA 90% of the time 10% of people "left dominant" - LCX supplies PDA Occlusion occurs LAD>RCA>LCX 1
Mitral Valve PM Two papillary muscles Anterolateral (AL) Posteromedial (PM) AL has dual blood supply LAD/LCX PM *single blood supply RCA (or LCX) Inferior infarction can lead to rupture of PM pap Severe mitral regurgitation Acute heart failure Cardiac Electrical System SA/AV node Usually supplied by RCA SA AV His LBB Purkinje Fibers SA Node - Right atrial wall AV Node -Interatrial Septum HIS - Interventricular septum 2 RBB
Cardiac Physiology Jason Ryan, MD, MPH Heart Volumes EDV End diastolic Volume Filling completed Contraction beginning ESV End systolic Volume Emptying completed Relaxation beginning Important Terms Venous Return (VR) Blood returned to left ventricle Should be equal to the cardiac output Total peripheral resistance Resistance to blood flow from peripheral structures Vasoconstriction T TPR Vasodilation TPR JPEG Important Terms Stroke Volume (SV) = EDV -ESV Ejection Fraction (EF) = SV / EDV Cardiac Output (CO) = SV * HR Blood Pressure Terms Systolic Blood Pressure (SBP) Largely determined by stroke volume Diastolic Blood Pressure (DBP) Largely determined by TPR Pulse pressure SBP - DBP Proportional to SV 3
Blood Pressure Terms Mean arterial pressure (MAP) DBP + 1/3 (SBP - DBP) • Example: SBP 120/80 MAP = 80 + 1/3 (40) 93.3 Cardiac Output Determinants 1. 2. 3. 4. Preload Afterload Contractility Heart rate To INCREASE Preload Cardiac Output Very important physiologyparameter Must rise to meet demands More cardiac output = more work/02 CO = HR x SV More beats per minute = more work More volume per beat = more work Preload Amount of blood loaded into left ventricle Also how much stretch is on fibers prior to contraction Some books say "length" instead of "stretch" More preload = more cardiac output More preload = more work the heart must do T02 required To DECREASE Preload 1. 2. 3. Add volume (blood, IVF) Slow heart rate more filling -5 more volume Constrict veins Veins force blood into heart Veins hold LARGE bloodvolume Response to blood loss -Y venous constriction Sympathetic stimulation -Y al receptors in veins 1. 2. 3. • • • 4 Remove volume (bleeding, dehydration) Raise heart rate (opposite mechanism above) Pool blood in veins Mechanism of action of nitrates Relieve angina Lower preload less work for heart
Preload Important Terms • LVEDV Volume of blood in the left ventricle when filled LVEDP Pressure in the left ventricle when filled To INCREASE Afterload 1. 2. Raise mean blood pressure Obstruct outflow of left ventricle Aortic stenosis, HCM Contractility How hard the heart muscle squeezes Ejection fraction = index of contractility Major regulator: sympathetic nervous system Also increases heart rate Afterload Forces resisting flow out of left ventricle Heart must squeeze to increase pressure Needs to open aortic valve push blood into aorta This is harder to do if: Blood pressure is high Aortic valve is stiff Something in the way: HCM, sub-aortic membrane To DECREASE Afterload 1. Lower the mean blood pressure 2. Treat aortic valve disease, HCM More afterload = more work More oxygen required To INCREASE Contractility Sympathetic nervous system activity Sympathetic innervation to heart Circulating catecholamines (epinephrine, norepinephrine) t calcium release from sarcoplasmic reticulum Triggers: stress, exercise Sympathomimetic drugs Dopamine, dobutamine, epinephrine, norepinephrine Digoxin Inhibits Na-K pump -Y t calcium in myocytes 5
To DECREASE Contractility Sympathetic system blocking drugs Beta blockers Calcium channel blockers Verapamil, diltiazem Less calcium for muscle contraction Heart failure Disease of myocytes Heart Rate t HR = stroke volume (less fillingtime) Heart Rate Heart Rate Sympathetic nervous system: THR and tcontractility Stroke volume rises with increased HR Heart Rate Heart Rate Increases cardiac output under physiologic conditions Mainly regulated by sympathetic nervous system Also increased by sympathomimetic drugs Decreased by beta blockers and calcium blockers Heart Rate THR = t cardiac output CO = SV * HR Heart Rate Heart Rate At pathologic heart rates t HR = CO High heart rate with arrhythmia can lead to UCC) CO = SV * HR Heart Rate 6
Work of the heart Myocardial 02 demand • Preload (LVEDV/P) Afterload (MAP) Contractility (EF) Heart Rate Hearts starved for 02 Reduce 02 demand Low output Need to increase work 7
Cardiovascular Response to Exercise Jason Ryan, MD, MPH Response to Exercise Process begins with muscle contraction ATP consumed -Y oxygen consumed (need more ATP) Result: Local hypoxia in muscle tissue Vasodilation occurs Multiple mediators released into plasma Adenosine generated from ATP consumption Lactate Carbon dioxide, potassium Lowers total peripheral resistance (TPR) Response to Exercise Blood Pressure Summary SBP rises More CO = more blood in arteries = more pressure Primary determinant systolic BP = cardiac output DBP decreases slightly or stays normal Local dilation of skeletal muscles Primary determinant diastolic BP = peripheral resistance Pulse pressure increases TPR goes down Response to Exercise Body's overall goal: Maximize perfusion skeletal muscles and heart Minimize perfusion all other areas • Initiator: Muscle hypoxia Mediator: Sympathetic nervous system Response to Exercise Sympathetic nervous system activated tcontractility (stroke volume) • THR Net result: t cardiac output Results in t systolic blood pressure (SBP) Vasoconstriction in some areas (gut, skin) Redistributes blood to important areas (i.e. heart/muscles) Response to Exercise Ejection Fraction LVEF increases More vigorous contraction Major impact: ESV decreases EDV effects minor/variable EDV - ESV EDV More preload but less filling time at fast heart rates 8
Response to Exercise Coronary Perfusion Fast HR shortens diastole LESS coronary filling time Coronary vasodilation increased blood flow Only way to get more oxygen Cannot extract more O Cardiac tissue extracts maximum oxygen from RBCs Cannot extract more to meet increased demand Lusitropy Lusitropy = myocardial relaxation Opposite of contractility Increased with exercise Contributes to increased preload -Y t cardiac output SERCA Sarco/endoplasmic reticulum Ca2+-ATPase Sympathetic stimulation phosphorylates PLB • Inactivates PLB (relieves inhibitoryeffect) Allows SERCA to uptake more calcium Response to Exercise Preload Preload rises with exercise Sympathetic stimulation -5 venous contraction • Increases preload/EDV Contributes to rise in cardiac output Along with increased heart rate and contractility Lusitropy Key regulatory protein: Phospholamban Inhibitor: sarcoplasmic reticulum Ca2+-ATPase (SERCA) Phosphorylated via beta adrenergic stimulation Stops inhibiting SERCA Result: SERCA takes up calcium -Y relaxation Exercise Begins Muscle Hypoxia Beta Adrenergic Stimulation PLB SERCA Sarcoplasmi Reticulum Heart T Contractility T HR 9 Vasodilation Sympatheti c Activation T Lusitropy Peripheral Vessels Venous UTPR (Afterload) U/- DBP Arteriole Constriction Constriction TPreload TEDV
Blood Flow Mechanics Jason Ryan, MD, MPH Flow Equations Velocity Area Velocity * Area = Flow (m/s) * (m2) = (m3/s) Pulse Pressure Systolic BP - diastolic BP Normal = 120 - 80 = 40mmHg Older patients = t pulse pressure Hypertensive patients = t pulse pressure Related to vessel compliance • compliance = t pulse pressure Flow Equations Ohm's Law V = I R For fluids: AP = Q X R CO = Q for body TPR = total peripheral resistance AP = CO *TPR Resistance and Compliance Resistance = resistance to flow Compliance = distensability of vessels Stiff Vessels Stretch Vessels T resistance resistance L compliance T compliance High resistance = low compliance (vice versa) Pulse Pressure Compliance = A volume / A pressure Stiff vessel compliance -5 t pulse pressure Small change in volume for given pressure applied to walls Stretchy vessel -5 t compliance pulse pressure Large change in volume for given pressure applied to walls C=AV/AP AP AV / C 10
Pulse Pressure Pulse pressure varies with vessel compliance Stiff vessels Ucompliance Distensible Vessel 120/80 Stiff Vessel 170/100 Total Peripheral Resistance Easy to push blood out of heart less 02required Resistance to flow more work for heart What resists forward flow out of heart? 1. Types of vessels (i.e. pipes/tubes) 2. Thickness of blood (viscosity) Types of Vessels Arterioles = "resistance vessels" Major determinant of total peripheral resistance Large pressure drop Vasoconstriction = t T PR Vasodilation = L TPR Flow Equation Total Peripheral Resistance AP = CO *TPR t resistance = t pressure to maintain flow t pressure = t cardiac work Types of Vessels Aorta: SBP 100mmHg Large arteries: Falls fewmmHg Small arteries: 10-2 OmmHg Arterioles: 35mmHg Capillaries: 25mmHg Viscosity Thickness of blood Low viscosity Anemia High viscosity Polycythemia Multiple myeloma Spherocytosis 11
Poiseuille's Law AP = Q* R AP = QXR AP 8 n (viscosity) L (length) Il r (radius) 4 Series and Parallel Circuits Human organs arranged in parallel Resistances add up differently in series than in parallel Changes in radius -Y large change in resistance Series and Parallel Circuits For two resistances (2 and 2), what is total R? 1 1 1 Rtotal RI R2 Parallel Flow Equation Series 1 R total 1 Rtotal 1 R 1 2 1 1 2 Flow Equation Body AP = Arterial pressure - right atrial pressure R = Total peripheral resistance (T PR) R = Systemic vascular resistance (SVR) Lungs AP = Pulmonary artery pressure - left atrial pressure R = Pulmonary vascular resistance (PVR) Used to calculate resistance, CO, or AP Often applied to body and lungs For both systems Q = Cardiac Output (CO) Mean Arterial Pressure Diastolic plus 1/3 (Systolic - Diastolic) Total body Arterial blood pressure = 120/80 mmHg Mean arterial pressure = 80 + 1/3 (40) = 93 mmHg Lungs Pulmonary artery pressure = 40/20 mmHg Mean pulmonary artery pressure = 20 + 1/3 (20) = 27 mmHg 12
Total Body AP = CO *TPR R TPR AP = MAP - RAP MAP = mean arterial pressure RAP = right atrial pressure • CO of 5L/min; BP 155/80 (MAP 105), RA 5 Lungs R = PVR AP = PA- LAP AP = CO *TPR PA = mean pulmonary artery pressure LAP = left atrialpressure • CO of 5L/min; PA40/10 (MAP 20), LA 5 PVR = TPR = AP = co MAP - RAP 5 105 -5 5 = 20 AP = co PA - LAP 5 20-5 5 Lung and Body Flow Variables Flow Resistance Start Pressure End Pressure AP Lung co PVR PA PA-LA Flow Properties of Blood Vessels Property Flow Area Velocity Resistance AP Highest Capillaries Large Arteries Arterioles Arterioles Flow = Vel * Area Body co TPR AoP Lowest Large arteries Capillaries Veins Veins Velocity and Area Flow = Velocity * Area Changes as blood moves through vessels Aorta —Y arterioles -5 capillaries veins Cardiac output moves through system (same flow) Different vessels different area, velocity Area t t, velocity Velocity Area Flow = Velocity * Area (m3/s) = (m/s) * (m2) Law of Laplace Wall tension or wall stress Applies to vessels and cardiac chambers T tension t 02 demand -5 ischemia/angina Tension cc 13
Wall Tension Afterload: Increases pressure in left ventricle Hypertension, aortic stenosis Will increase wall tension "Pressure overload" Tension cc Wall Tension Hypertrophy: Compensatorymechanism Will decrease wall tension Force distributed over more mass Occurs with chronic pressure/volume overload Tension Eccentric Hypertrophy Volume overload of leftventricle Aortic regurgitation Mitral regurgitation Cardiomyopathy Ischemic and non-ischemic Wall Tension Preload: Increases radius of leftventricle Chronicvalvular disease (aortic/mitral regurgitation) Will increase wall tension "Volume overload" Tension Eccentric Hypertrophy Longer myocytes Sarcomeres added in series Left ventricular mass increased Wall thickness NOT increased Normal LV Size Dilated LV Increased myocyte size Sarcomeres in series Normal wall thickness Concentric Hypertrophy Pressure overload Chronic Tt pressure in ventricle Sarcomeres added in parallel Left ventricular mass increased Wall thickness increased Normal LV Size 14 L LV Size Increased myocyte size Sarcomeres in parallel Increased wall thickness
Concentric Hypertrophy Classic causes: Hypertension, Aortic stenosis Both raise pressure inLV cavity Decreased compliance (stiff ventricle) Often seen in diastolic heart failure 15
Regulation of Blood Pressure Jason Ryan, MD, MPH Baroreceptors Blood pressure sensors via stretch Signal central nervous system (brain) Response via autonomic nervous system Sympathetic and parasympathetic Modify: Heart rate/contractility Arterial tone (vasoconstriction) Venous tone (more tone = more preload to ventricle) Renal renin release Baroreceptors Aortic arch Senses elevated blood pressure Poor sensing oflow blood pressure Carotid sinus Most important baroreceptor Modifies signals over wider range of blood pressure Senses low and high blood pressure Aortic Arch Blood Pressure Required for perfusion of tissues Varies with sodium/water intake Regulated by nervous system Baroreceptors Aortic arch and carotid sinus Quick response to changes in blood pressure Rapid response via autonomic nervous system Kidneys (renin release) Blood Pressure Control Sympathetic Parasympathetic Carotid Sinus Blood Pressure Aortic Arch CN X (Vagus) e Brain e Carotid sinus CN IX (GP) Veins [Arteries Constrict/Dilate Heart UHR Afferent = Arrive at the brain Efferent = Exit the brain Nucleus Solitarius 16
High Blood Pressure Sympathetic Parasympathetic Hemorrhage Sympathetic Parasympathetic Aortic Arch CN X (Vagus) 'TN Blood Pressure Veins Dilate Arteries Dilate Brain e Heart Blood Pressure Aortic Arch CN X (Vagus) e Brain Veins Constrict ries Constrict Heart Carotid sinus HR/Contractility Carotid sinus t HR/Contractility CN IX (GP) Kidney Salt/ Water Retention CN IX (GP) Kidney Carotid Occlusion Sympathetic Parasympathetic T Salt/ Water Retention Carotid Massage Syncope while shaving or buttoning shirt Aortic Arch CN X (Vagus) Sympathetic Parasympathetic Blood Pressure e Brain e Carotid sinus CN (GP) Veins Dilate Arteries Dilate Heart Blood Pressure Aortic Arch CN X (Vagus) e Brain e Carotid sinus CN IX (GP) Veins Constrict Arteries Constrict Heart THR Tricks carotid sinus into thinking T BP Result: HR, Vasodilation, BP Severing CN IX Sympatheti c Parasympathetic Tricks carotid sinus into thinking BP Result is T HR, Vasoconstriction, TBP Severing CN X Sympathetic Parasympathetic Aortic Arch CN X (Vagus) Blood Pressure e Brain Carotid sinus CN (GP) Veins Constrict rteries Constrict Heart THR Blood Pressure Aortic Arch CN X (Vagus) e Brain e Carotid sinus CN IX (GP) Veins Arteries Heart THR Tricks brain into thinking L BP Result is t HR, Vasoconstriction, TBP Vagotomy Unopposed Sympathetic Cardiac Stimulation Result is t HR 17
Summary of Techniques Technique Carotid Massage Carotid Occlusion Sever CN IX Sever CN X Interpretation tBP IBP IBP Result IHR,IBP THR, TBP THR, TBP THR Coronary Blood Flow 120 Aortic Pressure go Coronary Flow Time(s) • In tachycardia, less time in diastole -Y less flow Organ Circulation Regional Blood Flow Epicardium site of coronary arteries Subendocardium receives smallest amount blood flow Autoregulation Some tissue beds maintain constant blood flow t BP -Y t flow -5 vasoconstriction -5 flow (normal) Use local metabolites to sense blood pressure Organ Lung Liver Kidneys Heart Key Features 100% of Cardiac Output Largest Systemic Blood Flow Highest blood flow by weight Largest A02 (80%) t demand vasodilation Autoregulation Organ Heart Brain Kidneys Lungs Skeletal Muscle Skin Key Control Variables C02, Adenosine, NO C02, pH BP and NaCl feedback Hypoxia Vasoconstriction Lactate, adenosine, K+ Sympathetic stimulation Kidney, brain, heart: Excellent autoregulation systems Skin: Poor autoregulatory capacity 18
Capillary Fluid Exchange Two forces drive fluid into or out ofcapillaries Hydrostatic pressure (P) Molecules against capillaries walls Pushes fluid out Oncotic pressure (Il) Solutes (albumin) drawing fluid into capillaries Capillary Interstitial Space Capillary Fluid Exchange Hydrostatic pressure - fluid PUSHING against walls High pressure drives fluid TOWARD low pressure Oncotic pressure -solutes PULLING fluid in High pressure draws fluid AWAY from low pressure Pc (100) (50) Pi (50) Eli (30) Net Pressure (NP) = 50 - 20 = 30 Flow = (NP) Kf Edema Net Pressure (NP) Capillary Interstitial Space t capillary pressure, t Pc (heart failure) L plasma proteins, L [lc (nephrotic syndrome, liver failure) t capillary permeability, TKf (toxins, infections, burns) t interstitial osmotic pressure, t Hi (lymphatic blockage) Capillary Fluid Exchange Hydrostatic pressure - fluid PUSHING against walls High pressure drives fluid TOWARD low pressure Oncotic pressure -solutes PULLING fluid in High pressure draws fluid AWAY from low pressure Pc Pi Net Pressure (NP) = (Pc -Pi) + (Hi - MC) Flow = (NP) Kf Edema Excess fluid movement out of capillaries Tissue swelling Lungs: Pulmonary edema Systemic capillaries: Lower extremity edema James Heilman, MD 3rd Spacing Intracellular fluid - Istspace About 2/3 body fluid Extracellular fluid - 2nd space About 1/3 body fluid Third spacing - fluid where it should NOT be Pleural effusions Ascites Cerebral edema Low intravascular volume/High total volume Occurs post-op, sepsis 19
Pressure Volume Loops Jason Ryan, MD, MPH PV Loops LVV01 Time PV Loops Time LVVol PV Loops Time PV Loops Time EDP - Diastole LV Vol ESV 20 LVVol ESPVR EDPVR LVV01 Systole EDV
PV Loop Parameters Changes in preload Changes in afterload Changes in contractility Changes in compliance • In reality, these are inter-related Example: t preload t contractility (Frank-Starling) roke Volume Preload Changes Increase Afterload Changes Increase Afterload Preload t EDV t sv t EF (slightly) SV = EDV - ESV EF = EDV - ESV EDV t ESV LEF EF = EDV - ESV EDV Preload Changes Decrease Afterload Changes Decrease 21 EDV EF (slightly) SV = EDV - ESV EF EDV - ESV EDV ESV tsv TEF EF = EDV - ESV EDV
Contractility Changes Decrease ESP VR I Compliance Changes Decreased Compliance t ESV EF = EDV - ESV EDV UEDV t EDP Contractility Changes Increase Work of the Heart More area = More work Aortic Stenosis LV vol 22 ESV t sv EF = EDV - ESV EDV EDPVR Commonly Tested PV Loops Aortic Stenosis Mitral Regurgitation Aortic Regurgitation Mitral Stenosis
Mitral Regurgitation Isovolumic Contraction Disrupted LV vol Mitral Stenosis Ventricle can't fill properly LVV01 Aortic Regurgitation LVV01 23
Wiggers' Jason Ryan, MD, MPH Diagram Wiggers' Diagram Aorta LV Heart Sounds Venous Pressure—y Left Ventricular Volume Wiggers' Diagram Aorta LV LV Volume Heart Sounds Venous EKG Normal Heart Aorta LV Diseased Heart Aortic Stenosis 24
Diseased Heart Normal Heart Mitral Stenosis Diseased Heart Normal Heart Aortic Regurgitation Diseased Heart Normal Heart Mitral Regurgitation 25
Atrial contracti on Pressure goes up Venous Pressure Tracings Jason Ryan, MD, MPH Venous Pressure Atrial relaxation Wiggers' Diagram Venous Pressure a c x Venous Pressure Tricuspid valve TV Closes a c x TV opens a c TV closes TV opens Pressure Falls Venous filling Pressure rises TV Closes a c x RV filling RV Relaxation a wave = Atrial contraction v wave = Venous filling c wave = triCuspid valve x descent = atrial relaXation y descent = emptying of the atrium Aorta LV LV Volume Heart Sounds Venous No RV filling RV Contraction Classic Findings Large a wave Cannon a wave Absent a waves Large v waves 26
Large a wave Tricuspid stenosis a c x Absent a wave Atrial fibrillation a c x High Yield Findings Large a wave (increased atrial contraction pressure) Tricuspid stenosis Right heart failure/Pulmonary hypertension Cannon a wave (atria against closed tricuspid valve) Complete heart block PAC/PVC Ventricular tachycardia Absent a wave (no organized atrial contraction) Atrial fibrillation Giant V waves Tricuspid regurgitation Cannon a wave AV dissociation a c x Giant v wave Tricuspid regurgitation a c x Left Atrial Pressure a c x 27
Starling Curves Jason Ryan, MD, MPH Frank-Starling Curve Left and Right Shifts Stroke Volume T Contractility Peripheral Resistance (afterload) Normal U Contractility t Peripheral Resistance (afterload) Preload (LVEDP, LVEDV) Venous Return Curve Right Atrial Pressure Venous Return or Cardiac Output Frank-Starling Curve Stroke Volume Preload (LVEDP, LVEDV) Frank-Starling Curve Left and Right Shifts Contractility Increase: Exercise, inotropes Decrease: Myocardial infarction, heart failure Peripheral resistance: Total peripheral resistance (TPR) Systemic vascular resistance (SVR) Increase: Vasopressors Decrease: Vasodilators, sepsis Right Atrial Pressure 28
Venous Return Curve Left and Right Shifts Venous Return or Cardiac Output Mean Systemic Filling Pressure (MSFP) Pressure if heart stops Right Atrial Pressure Venous Return Curve Changes in Slope L Total peripheral resistance Venous Return or Cardiac Output Normal t Total peripheral resistance Right Atrial Pressure TPR change shifts curve right/left No change in MSFP Result: change in slope of Venous Return curve * Black = normal Venous Return Curve Volume Venous Tone t Blood Volume Venous constriction (T tone) Venous Return or Cardiac Output Normal U Blood Volume Venous dilation (J tone) Right Atrial Pressure Combined Curves Starling and Venous Return co or Right Atrial Pressure Hemorrhage or Preload Blood loss t TPR t Contractility Heart Failure co or Right Atrial Pressure or Preload * Black = normal Ucontractility t TPR t Fluid volume co or VR 29 Right Atrial Pressure or Preload
Exercise Decreased afterload (TPR) Venous contraction • Increased contractility Net result = increased CO Vasopressors • Increased afterload (TPR) Alters VR and Starling Curves Net result = decreased CO AV Fistulas Decreased afterload (TPR) Increased contractility Venous contraction Net result = increased CO Combined Curves Starling and Venous Return co or VR 30 15 10 5 For a patient on starling curve A with a MSFP of 10 what is the cardiac output? 10 12 14 Right Atrial Pressure * Black = normal
Atherosclerosis Jason Ryan, MD, MPH Atherosclerosis Plaque accumulation in arterial walls Chronic inflammatory process • Involves macrophages, T-cells Accumulation of lipoproteins especially LDL Underlying cause of many diseases Myocardial infarction Stroke Peripheral vascular disease Arterial Structure Intima Single layer of endothelial cells Basement membrane Media Smooth muscle cells Elastin Adventicia Connective tissue Vasa vasorum (blood supply to artery wall) Nerve fibers Vocabulary Arteriosclerosis Hardening of arteries Hyaline Hyperplastic Atherosclerosis Form of arteriosclerosis Most common type OpenStax College /Wikipedia Type of Arteries Elastic Nephron/Wikipedia A. Rad etal. /Wikipedia Bruce Blaus/Wikip edia Large amounts of elastin in media layer Expansion in systole, contraction in diastole Aorta, carotid arteries, iliac arteries Muscular Layers of smooth muscle cells Vasoconstriction/vasodilation to modify blood flow Arterioles: smallest muscular vessels (most flow resistance) 31
Atherosclerosis Large elastic arteries Aorta, carotid arteries, iliac arteries Medium-sized muscular arteries Coronary, popliteal Luke Guthman /Wikipedia Atherosclerosis Pathogenesis Branch points and vessel origins (ostia) Common sites of plaque Turbulent flow -5 endothelial stress Atherosclerosis Pathogenesis Chronic inflammation LDL oxidized from free radicals Damages endothelium, smooth muscle Macrophages release cytokines Atherosclerosis Pathogenesis Endothelial injury or dysfunction Details incompletely understood Believed to be related to risk factors Cigarette smoke High blood pressure High cholesterol Atherosclerosis Pathogenesis Lipids LDL accumulation in intima Oxidized by free radicals Oxidized LDL scavenged by macrophages Cannot be degraded Macrophages become foam cells Macrophage Foam cell Public Domain Atherosclerosis Pathogenesis Smooth muscle cells proliferate in intima Lay down extracellular matrix Key growth factor: PDFG Platelet-derived growth factor OpenStax College/Wikipedia 32
Atheroma Growth Fatty streaks Macrophages filled with lipids Form line (steak) along vessel lumen Do not impair blood flow Can be seen in children, adolescents Not all progress Fatty streak Npatchett/Wi ki pedi a Advanced/vulnerable Atheroma Growth Atherosclerotic plaques Intima thickens Lipids accumulate Usually patchy along vessel wall Rarely involve entire vessel wall Usually eccentric Npatchett/Wikipedia Locations Abdominal aorta (large vessel) Coronary arteries Popliteal arteries • Internal carotid Circle of Willis Normal Fatty streak Fibrofatty plaque NP atchett/Wiki ped i a O Public Domai n Atherosclerosis Complications Ischemia Plaque rupture Exposes thrombogenic substances Clot formation May cause acute vessel closure (STEMI) Thrombus may embolize (stroke from carotid plaque) Atherosclerosis Complications Hemorrhage into plaque Lesions: proliferating small vessels ("neovascularization") Contained rupture may suddenly expand lesion Aneurysm Lesions may damage underlying media Plaque associated with abdominal aortic aneurysms Public Domain 33
Dystrophic Calcification Commonly seen in atheroma Result of chronic inflammation Basis for "coronary CT scans" White Infarct Renal Infarction Ryan Johnson/ Fli kr Red Infarct Lung Infarction Yale Rosen/Wikipedia Infarction Area of ischemic necrosis Two types: white and red White infarcts Occlusion of arterial supply to a solid organ Common in heart, kidneys, spleen Limited blood seepage from healthy tissue Tissue becomes pale (white) Red Infarcts Hemorrhagic Infarct Blood enters ischemic tissue Blockage of venous drainage Testicular torsion Tissues with dual circulation Blood flow from 2nd supply floods ischemic area Classic location: Lung (diffuse blood supply) Small intestine Flow re-established to necrotic area Angioplasty restores flow in coronary artery 34
Cardiac Ischemia Jason Ryan, MD, MPH Stable Angina Stable atherosclerotic plaque No plaque ulceration No thrombus Must occlude —75% of lumen to cause symptoms Cardiac Ischemia Caused by coronary atherosclerosis 02 SUPPLY 02 DEMAND = ISCHEMIA Typical symptoms Chest pain (angina) Dyspnea Diaphoresis Freestocks. or g Acute Coronary Syndromes Plaque rupture thrombus formation Subtotal occlusion Unstable angina Non-ST elevation myocardial infarction Total occlusion (100%) ST-elevation myocardial infarction (ST EMI) o Sudden Death 000 NO SYMPTOMS SYMPTOMS WITH EXERTION (EXERTIONAL ANGINA) Subtotal Occlusion Risk Factors Total Occlusion Common complication of CAD Plaque rupture -5 arrhythmias CAD is most common cause of sudden death adults Younger patients: Hypertrophic cardiomyopathy (HCM) Major risk is prior coronary disease Coronary risk equivalents Diabetes Peripheral artery disease Chronic kidney disease 35
Risk Factors Hypertension Hyperlipidemia Family History (1 relative, M
Ischemic EKG changes T wave inversions Subendocardial Ischemia Hyperacute T waves Seen in transmural ischemia Early sign of ischemia Seen before ST elevations Ischemic EKG changes ST Elevations Seen only with transmural ischemia Evolution of EKG changes STEMI Normal Acute Hours Q wave 1-2 Days 3-7 Days > 7 Days Poor R Wave Progression R wave increases (progresses) in size VI-V6 Normally R>S waves seen by leadV3 Poor progression seen in anterior ischemia Acute or prior infarction 37
Terminology Revascularization Angioplasty Coronary stenting Coronary bypass surgery Coronary Stents Angioplasty: Reshape vessel Balloon angioplasty: Balloon inflation to open vessel Percutaneous Coronary Intervention (PCI) Stent placement About 600,000 stents/year implanted US vs Revascularization Coronary angiogram: Before Coronary angiogram: After Wikipedia/Public Domain 38
CABG Coronary Artery Bypass Surgery • "Bypass Surgery" Left Internal Mammary Artery (LIMA) Graft Saphenous (leg) Vein Grafts Radial (arm) Artery Grafts Patrick J. Lynch/ Wikipedia Revascularization Major Indications Angina Myocardial infarction Systolic dysfunction Hibernating myocardium Complications of Ischemia First 4 days Arrhythmia 5 - 10 days Free wall rupture Tamponade Papillary muscle rupture VSD (septal rupture) Weeks later Dressler's syndrome Aneurysm LV Thrombus/CVA Patrick J. Lynch/Wikipedia Ischemic Pathologic Changes Myocardium Zero to 4 hrs No changes! 4 - 12 hrs Gross: Mottled Micro: Necrosis, edema, hemorrhage 12-24 hrs Gross: Hyperemia Micro: Surrounding tissue inflammation 5 - 10 days Gross: Central yellowing Micro: Granulation tissue 7 weeks Gross: Gray-white scar Micro: Scar Cause of Death 0 - 4 days after MI 39
Cause of Death 5-10 days after MI Free wall rupture Usually fatal - sudden death May lead to tamponade Papillary muscle rupture Acute mitral regurgitation (holosystolic murmur) Heart failure, respiratory distress More common inferior MIS Septal rupture - VSD Loud, holosystolic murmur (thrill) Hypotension, right heart failure (t JVP, edema) Ventricular Pseudoaneurysm Rupture contained by pericardium/scar tissue Not a true aneurysm No endocardium or myocardium May rupture Presents as chest pain ordyspnea Often seen in the inferior wall Occurs earlier (
Secondary Prevention Several proven therapies for riskreduction Aspirin Statins Atorvastatin, Rosuvastatin Beta blockers Used in patients with prior infarction (STEMI/NSTEMI) Ragesoss/Wi kipedia Stent Complications Thrombosis Acute closure of stent Same as STEMI: life-threatening event Dual anti-platelet therapy for prevention Associated with missed medication doses Stent Complications Restenosis Slow, steady growth of scar tissue over stent • "Neo-intimal hyperplasia" Re-occlusion of vessel Rarely life-threatening Slow, steady return of angina Most stents coated "drug eluting stents" Metal stent covered with polymer Polymer impregnated with drug to prevent tissue growth Sirolimus Stent Thrombosis Prevention • "Dual antiplatelet therapy/' Typically one year of: Aspirin Clopidogrel, Prasugrel or Ticagrelor After one year, stent metal no longer exposed to blood "Endothelialization" Risk ofthrombosis is lower (but not zero) Most patients take aspirin only 41
ST-Elevation Myocardial Infarction (STEMI) Jason Ryan, MD, MPH STEMI Transmural ischemia Transmural Ischemia Complete Occlusion ST-elevation Myocardial Infarction Ulcerated Plaque - Thrombus Complete occlusion distal blood flow No STEMI STEMI Atherosclerotic plaque rupture Thrombus formation Ischemic chest pain ST-elevations on ECG STEMI .4 Leads go together ST Elevations - Anterior 42
Leads go together ST Elevations - Anterior Leads go together STEIevations - Lateral Leads go together ST Elevations - Inferior Leads go together STEIevations - Lateral Leads go together ST Elevations - Inferior Coronary Artery Territories Left anterior descending artery Anterior -5 VI-V4 Left circumflex artery Lateral 1, L, V5, V6 Posterior descending artery Inferior -5 Il, Ill, F Branch of right coronary artery 90% LCX 10% 43
Special Complications Inferior MI Right ventricular infarcti on Loss of right ventricular contractility Elevated jugular venous pressure Decreased preload to left ventricle -5 hypotension Diagnosis: Right sided chest leads Special Complications Inferior MI Sinus bradycardia and heart block Vagal stimulation from inferior wall ischemia M, ..i. Al....i.Li.i....lA Posterior Myocardial Infarction V6 vs Jmarchn/Wikipedia Left Main Occlusion STEMI Special Subtypes Left main ST-elevation aVR Diffuse ST depressions Posterior Anterior ST depressions with standard leads ST-elevation in posterior leads (V7-V9) 44
Treatment of STEMI "Time is muscle" Coronary artery occluded by thrombus Longer occlusion -5 more muscle dies More likely the patient may die More heart failure symptoms More future hospitalization for heart disease Medical emergency Treatment of STEMI Time matters Medical therapy is supportive Given while working to open artery Remember: this is a thrombotic problem Aspirin to inhibit platelet aggregation Heparin to inhibit clot formation This is also an ischemic problem Beta blockers to reduce 02 demand Nitrates to reduce 02 demand Other ST EMI Treatments Clopidogrel ADP receptor blocker Inhibits platelets Eptifibatide IIB/IIIA receptor blocker Inhibits platelets Bivalirudin Direct thrombin inhibitor Inhibits clot formation Treatment of STEMI Main objective is to open the artery 'Revascularization" Option 1: Emergency angioplasty Mechanical opening of artery Should be done
Typical ST EMI Course Arrival in ER with chest pain 5:42pm EKG done 5:54pm STEMI identified Meds given in ER Aspirin Metoprolol Nitro drip Heparin bolus • tPAgiven based on weight 6:07pm IV push Door to needle time 25min (ideal
NSTEMI and Unstable Angina Jason Ryan, MD, MPH Subendocardial Ischemia Subendocardial Ischemia Subtotal Occlusion Limited distal flow Cardiac Biomarkers Biomarkers spill into blood with cardiac injury Most common marker used: Troponin I or T Increase 2-4 hours after MI Stay elevated for weeks CK-MB also used Increase 4-6 hours after MI Normalize within 2-3 days NSTEMI Non-ST-Elevation Myocardial Infarction Atherosclerotic plaque rupture Thrombus formation Subtotal (
Cardiac Biomarkers Some AST found in cardiac cells Abdominal pain with isolated T AST could be MI Bodyparts3D/Wikimedia Commons Typical NSTEMI Course Presents to ER with chest pain Biomarkers elevated Medical Therapy Aspirin Metoprolol Heparin drip Admitted to cardiac floor Hospital day 2 angiography 90% blockage of LAD -5 Stent Unstable Angina Diagnosis largely based on patient history Chest pain increasing in frequency/intensity Chest pain at rest ECG may show ST depressions or T wave inversions Treatment is same as forNSTEMI Condition often called "UA/NSTEMI" Treatment of NSTEMI Thrombotic and ischemic syndrome (like STEMI) Unlike STEMI: No "ticking clock" Subtotal occlusion Some blood flow to distal myocardium No emergency angioplasty No benefit to thrombolysis Aspirin Beta blocker Heparin Angioplasty (non-emergent) Unstable Angina Atherosclerotic plaque rupture Thrombus formation Subtotal (
Stable Angina Jason Ryan, MD, MPH Stable Angina Symptoms generally absent until —75% occlusion Distal arteriolar dilation -5 normal flow if
Medical Therapy for Ischemia Nitrates Converted to nitric oxide -5 vasodilation Predominant mechanism is venous dilation 02 Supply 102-Supp1LDilate coronary arteries Increase diastole Nitrates preload -5 U cardiac output 02 Demand 102 Demand Heart rate Contractility Afterload Preload Bigger veins hold more blood Takes blood away from left ventricle Lowers preload (LVEDV) Also arterial vasodilation (art
Nitrate Tolerance Drug stops working after frequentuse Avoid continuous us for more than 24 hours Does not occur with daily isosorbide mononitrate o Jpeterso n 101 /Wi kipedia Monday Disease Workers in nitroglycerin manufacturing facilities Regular exposure to NTG in the workplace Leads to the development of tolerance Over the weekend workers lose the tolerance "Monday morning headache" phenomenon Re-exposed on Monday Prominentvasodilation Tachycardia, dizziness, and a headache Beta Blockers For angina, generally use cardioselective (ßl) drugs Metoprolol, atenolol Some beta blockers are partial agonists Pindolol, Acebutolol Don't use in angina Nitrate Withdrawal Nitrate withdrawal (rebound) after discontinuation Occurs when using large doses of long-acting nitrates Angina frequency will increase Freestocks.org Beta Blockers Slow heart rate and decrease contractility • Increase preload (LVEDV) Slower heart rate = more filling time Increase 02 demand Blunts some beneficial effect Reduced blood pressure (L afterload) Net effect = less 02 demand Calcium Channel Blockers Three major classes of calcium antagonists dihydropyridines (nifedipine) phenylalkylamines (verapamil) benzothiazepines (diltiazem) Vasodilators and negative inotropes 51
Calcium Channel Blockers Nifedipine: vasodilator Lower blood pressure Reduce afterload Dilate coronary arteries May cause reflex tachycardia Verapamil/diltiazem: negative inotropes Similar to beta blockers Reduced heart rate/contractility Can precipitate acute heart failure if LVEF very low Antianginal Therapy Calcium Channel Blockers Antianginal Therapy Nitrates/ Beta Blockers Nitrates + Beta blockers Supply Coronary vasodilation Duration diastole Demand Preload Afterload Contractility Heart Rate Nitrates Increase reflex Decrease Decrease T reflex T reflex Increase Increase Decrease Decrease Decrease Beta blockers Increase Decrease Decrease Supply Coronary vasodilation Duration diastole Demand Preload Afterload Contractility Heart Rate Verapamil Increase Increase Decrease Decrease Decrease Diltiazem Increase Increase Decrease Decrease Decrease Nifedipine Increase reflex Decrease T reflex T reflex Ranolazine Constipation, dizziness, headache QT prolongation (blockade of K channels) Prolong QT Ranolazine • Inhibits late sodium current Reduces calcium overload -5 high wall tension Reduces wall tension and 02 demand Late Na influx Phase O Ca Variant (Prinzmetal) Angina • Ischemia from vasospasm Not caused by atherosclerotic narrowing Often artery is "clean" with no stenosis May also occur near sites of mild atherosclerosis Spontaneous episodes of angina Transient myocardial ischemia ST-segment elevation on ECG 52
Variant (Prinzmetal) Angina Episodes usually at rest Midnight to early morning Sometimes symptoms improve withexertion Associated with smoking Variant (Prinzmetal) Angina Treatment Quit smoking Calcium channel blockers, nitrates Vasodilators Dilate coronary arteries, oppose spasm Avoid propranolol Non selective blocker Can cause unopposed alpha stimulation Symptoms may worsen Coronary Steal Stenotic vessels Significant (>75%) narrowing Pixabay/Public Domain Arterioles maximally dilated to maintain flow Normal vessels No or minimal narrowing Arterioles NOT maximally dilated Variant (Prinzmetal) Angina Diagnosis Usually based on history Intracoronary ergonovine Acts on smooth muscle serotonergic (5-HT2) receptors Can be administered during angiography Vasospasm visualized on angiogram Intracoronary acetylcholine Acts on endothelial muscarinic receptors Healthy endothelium vasodilation via nitric oxide Endothelial dysfunction -5 vasoconstriction Vasospasm visualized on angiogram Coronary Steal Mechanism of angina • Induced by drugs Blood flow increased to healthy vessels Blood flow decreased in stenotic vessels Blood "stolen" from diseased coronary vessels Coronary Steal Vasodilator administered Stenotic vessels no response Arterioles already maximally dilated Normal vessels vasodilation Flow increases to normal vessels Flow decreases to abnormal vessels Results: ischemia due to coronarysteal 53
Coronary Steal Rarely seen with nitrates, nifedipine Key principle for chemical stress tests Adenosine, persantine, regadenoson Potent, short-acting vasodilators Brief L in blood flow to stenotic vessels ischemia Nuclear tracers can detect blood flow 54
SA EKG Basics Jason Ryan, MD, MPH AV Node HIS Bundle Bundle Branches Purkinje Fibers SA AV HIS Bundle Bundle Branches HIS Bundle Bundle Branches Purkinje Fibers Atrial Depolarization Depolarization EKG Electrical Activity LBB His RBB Purkinje Fibers urkinje Fibers EKG EKG Electrical Activity 55
EKG Electrical Activity AVR EKGs Key Principles 2 AVL 111 AVF #1: Waves represent repolarization/depolarization #2: EKGs have 12 leads Each lead watches the same thing Each lead watches from different vantage point Electrical activity toward lead = upward deflection Electrical activity away from lead = negative deflection Conduction Velocities SLOWEST conduction is through AVnode Very important so ventricle has time to fill Purkinje fibers fastest conduction Purkinje > Atria > Vent > AV node EKG Pacemakers SA node is dominant pacemaker of the heart Other pacemakers exist but are slower • If SA node fails, others takeover SA node (60-100 bpm) AVnode (40-60 bpm) HIS (25-40 bpm) Bundle branches (25-40 bpm) Purkinje fibers (25-40 bpm) Determining Heart Rate 3 - 5 big boxes between QRS complex 56 5 300 150 100 75 60 50
QRS Axis His RBB QRS Axis +1800 — 900 +900 LBB urkinje Fi bers Left Axis Deviation LBBB Ventri cular Rhythm 00 Normal QRS Axis -30 and +90 degrees Ri QRS Axis -900 +1800 +900 QRS Axis —900 ht Axis Deviation RBBB RVH +1800 +900 Axis Quick Method First, glance at aVr. • It should be negative • If upright, suspect limb lead reversal 00 Normal QRS Axis -30 and +90 degrees Left Axis Deviation LBBB Ventricular Rhythm 00 Normal QRS Axis -30 and +90 degrees Determining Axis —900 +1800 RAD Lead I 00 Normal Axis -30 to +90 +900 a 57 Normal
Axis Quick Method • If leads I and Il are both positive, axis is normal Lead I Axis 0 to 900 Lead 11 Axis Quick Method Axis Quick Method For left axis deviation: All you need is lead Il Lead I Axis -30 to -900 Lead Il Lead 11 Axis Quick Method Look at aVr: Make sure its negative Look at I, Il: If both positive, axis is normal • If Il is negative: LAD • If I is negative: RAD Axis 0 to -300 Physiologic Left Axis For right axis deviation: All you need is lead I Negative = RAD Lead I Lead 11 PR Interval Normal PR 120-200m Short PR - WPW Normal Phys Left Left Right Axis 90 to 1800 Prolonged PR 10 AV block Lead I Lead Il QRS Interval Normal QRS
Qt Interval Normal Qt Short Qt: Hy-pgc-calc-emia Prolonged Qt Hypocalcemia Drugs LQTS Torsade de Pointes Feared outcome of Qt prolongation Results in cardiac arrest Antiarrhythmic drugs Hypokalemia, hypomagnesemia Rarely from hypocalcemia Congenital Long Qt Syndrome Family history of sudden death (torsades) Classic scenario: Young patient recurrent "seizures" EKG shows long Qt interval Jervell and Lange-Nielsen Syndrome Norway and Sweden Congenital deafness Calcium Myocyte Action Potential Phase 1 (out) Omv Phase 0 Na+ (in) -85mv Phase 2 K+ (out) Ca+ (in) Phase 3 K+ (out) Phase 4 Congenital Long Qt Syndrome Rare genetic disorder Abnormal K/Na channels Prolonged QT Acquired Long Qt Syndrome Antiarrhythmic drugs Levofloxacin (antibiotic) Haldol (antipsychotic) Many other drugs Congenital LQTS: need to avoid these drugs 59
T waves Peaked T waves Early ischemia (hyperacute) U waves Origin unclear May represent repolarization of Purkinje fibers Can be normal but also seen in hypokalemia 60
EKGs You Should Know High Yield EKGs Jason Ryan, MD, MPH Step 1: Find the p waves Are p waves present? Step 2: Regular or Irregular Distance between QRS complexes (R-R intervals) Regular Irregular 1. 2. 3. 4. 5. 6. 7. 8. 9. Sinus rhythm Atrial Fibrillation/ Flutter Ischemia: ST elevations, ST depressions Left bundle branch block Right bundle branch block PAC/PVC 1st 2nd 3rd degree AV block Ventricular tachycardia Ventricularfibrillation/Torsades Sinus p waves Originate in sinus node Upright in leads Il, Ill, F Steps 1 & 2 P waves present, regularrhythm Sinus rhythm Rare: atrial tachycardia, atrial rhythm No p waves, irregular rhythm Atrial fibrillation - irregularly irregular Atrial flutter with variable block 61
Steps 1 & 2 P waves present, irregularrhythm Sinus rhythm with PACs Multifocal atrial tachycardia Sinus with AV block No p waves, regular rhythm Hidden p waves: retrograde Supraventricular tachycardias (SVTs) Ven tricular tachycardia QRS Interval Normal QRS Right Bundle Branch Block Left Bundle Branch Block Step 5: ST segments T wave abnormali ties Inverted: ischemia Peaked: Early ischemia, hyperkalemia (TK) Flat/U waves: Hypokalemia (1K) ST Depression Subendocardial ischemia ST Elevation Transmural ischemia Step 3: Wide or narrow Narrow QRS (
Right Bundle Branch Block Atrial Fibrillation Ventricular Tachycardia Left Bundle Branch Block Atrial Flutter Ventricular Tachycardia 63
Torsades de pointes • t risk with prolonged Qt interval Antiarrhythmic drugs Congenital long Qt syndrome Antibiotics (erythromycin, quiniolones) Hypokalemia Hypomagnesemia Rarelyhypocalcemia PAC and PVC ml 64
Cardiac Action Potentials Jason Ryan, MD, MPH Myocyte Action Potential Atrial/ventricular myocytes Cardiac Action Potential Changes in membrane voltage of cell Transmit electrical signals through heart Triggers contraction ofmyocytes Phase 4 Resting potential: about -85mV Constant outward leak of K + • "Inward rectifier channels" Na+ and Ca2+ channels are closed Phase 1 K+ (out) 0 mv Phase 0 Na+ (in) -85mv Phase 0 Phase 2 Ca+ (in) K+ (out) Phase 3 K+ (out) Phase 4 Phase O Phase 4 Phase 1 Phase 4 Nearby myocyte raise membrane potential Gap junctions Rising potential opens "Fase' Na+ channels Threshold potential reached (about -70mV) Large Na+ current rapid depolarization Membrane potential overshoots (>0mV) Fast Na+ channels close Class I antiarrhythmic drugs: block Na channels Membrane potential is positive K + channels open Outward flow of K + returns membrane to —0mV Phase 1 65
Phase 2 L-type Ca2+ channels open -5 inward Ca2+ current Contraction trigger: excitation-contraction coupling K + leaks out (down concentration gradient) Delayed rectifier K+channels Balanced flow in/out = plateau of membrane charge Verapamil/Diltiazem = block L-type Ca channels Phase 2 Skeletal Muscle No plateau (phase 2) No gap junctions Each cell has its own NMJ Na+ Myocyte Action Potential Atrial/ventricular myocytes Similar AP in HIS, bundle branches, Purkinje fibers Phase 3 Ca2+ channels inactivated Persistent outflow of K* Resting potential back to -85 mV Class Ill antiarrhvthmic drugs: block K channels Phase 3 Refractory Period Phase 0 until next possible depolarization Determines how fast myocyte can conduct Many antiarrhythmic drugs prolong refractory period Refractory Period Pacemaker Action Potential SA node, AV node 0 mv Phase 0 Ca Threshold Phase 3 -40mv -85mv 66 Phase 4 f (Na)
Pacemaker Action Potential SA node, AV node Funny current (pacemaker current) Spontaneous flow of Na+ About -40 mV: threshold potential L-type Ca2+ channels open -5 depolarize cell Delayed rectifier K + channels open Return cell to -60 mV Pacemaker Action Potential SA node, AV node Any drug that slows this AP may cause two effects: Slower heart rate (sinus node) Slower AV conduction (AV node) Omv Phase 0 Ca "Ihreshold -40mv -85mv Pacemaker Action Potential SA node, AV node Verapamil/Diltiazem = block L-type Ca channels Slow rate of sinus depolarization (slow heart rate) Slow AV node conduction Omv Phase 0 Ca Threshold -40mv -85mv Pacemaker Action Potential SA node, AV node Automaticity Do not require stimulation to initiate action potential Capable of self-initiated depolarization No fast Na+ channel activity Fewer inward rectifier channels Membrane potential never lower than —60 mV Fast Na+ channels need —85 mV to function Pacemaker Action Potential SA node, AV node Two key drug classes that affect pacemaker AP Calcium channel blockers (Verapamil/Diltiazem) Beta blockers Omv Phase 0 Ca Threshold -40mv -85mv Beta Blockers Modify slope of phase 4 Less slope -5 longer to reach threshold -5 UHR Normal 67 Beta Blocker Slower phase 4 (less slope)
Beta Blockers Also prolong repolarization Slow AV node conduction Normal Beta Blocker Slower repolarization (slows conduction) Pacemakers Many cardiac cells capable of automaticity SA node normally dominates Fastest rise in phase 4 Controls other pacemaker cells Pacemakers: SA Node > AV Node > Bundle of HIS SA node (60-100 bpm) AVnode (40-60 bpm) HIS (25-40 bpm) Slope of Phase 4 Sinus Node Changes in slope modify heart rate Decrease slope (slower rise) Parasympathetic NS, beta blockers, adenosine • Increased slope (faster rise) Sympathetic NS, sympathomimetic drugs Phase 4 68
AV and Bundle Branch Blocks Jason Ryan, MD, MPH AV Blocks Slowed or blocked conduction atria ventricles Can cause prolonged PRinterval Can cause non-conducted p wave Non-conducted P wave Prolonged PR Interval AV Blocks Anatomy Caused by disease in AV conduction system AVnode HIS -5 Bundle Branches Purkinje fibers Divided into two causes AV node disease HIS-Purkinje disease AV Node HIS Bundle Bundle Branches Purkinje Fibers Atrial Depolarization AV Blocks Symptoms SA AV HIS Bundle Depolarization Bundle Branches Purkinje Fi bers Often incidentally noted on EKG Especially milder forms with few/no non-conducted p waves Can cause bradycardia Occurs when many or all p waves not conducted Fatigue, dizziness, syncope Symptomatic AVblock often treated with a pacemaker AV Blocks Anatomy AV node disease Usually less dangerous Conduction improves with exertion (sympathetic activity) HIS-Purkinje disease More dangerous Usually does not improve with exertion Often progresses to complete heart block Often requires a pacemaker 69
AV Blocks Four Types Type 1 Prolongation of PR interval only All p waves conducted Type Il Some p waves conducted Some p waves NOT conducted Two sub-types: Mobitz I and Mobitz Il Type Ill No impulse conduction from atria to ventricles 2nd degree AVB Mobitz I/ Wenckebach Block usually in AV Node Progressive PR prolongation Grouped Beating RR intervals NOT regular Similar causes as Istdegree AVblock 2nd degree AVB Mobitz Il Block usually in the HIS-Purkinje System Often seen with bundle branch block Usually symptomatic Dizziness, syncope 1st degree AV Block Prolonged PR (normal
3rd degree AVB Block usually in the HIS-Purkinje System Regular RR intervals excludes Wenckebach Vocabulary Complete heart block Impulses cannot be transmitted from atria to ventricle AV dissociation Atria and ventricular depolarization uncoupled ("dissociated") Can be cased by complete heart block Also occurs if ventricular rate > sinus rate (no heart block) Seen in ventricular tachycardia and other rhythms Ventricular Tachycardia Lyme Disease Spirochete infection with Borrelia burgdorferi Stage 2: Lyme carditis Varying degrees of AV block 1st 2nd 3rd AV block improves with antibiotics Image courtesy of Wikipedia/Public Domain Ventricular Tachycardia Escape Rhythm SA node: Dominant (fastest) pacemaker Heart block: SA cannot send impulses to ventricles Other pacemakers exist but are slower SA node (60-100 bpm) AVnode (40-60 bpm) HIS (25-40 bpm) Bundle branches (25-40 bpm) Purkinje fibers (25-40 bpm) 71
Escape Rhythm Heart block: lower pacemaker depolarizes ventricles "Escape rhythm" Rate of lower pacemaker determines symptoms Very slow: dizziness, syncope, hypotension Less slow: fatigue, exercise intolerance Causes of Heart Block Drugs Beta blockers, calcium channel blockers Digoxin High vagal tone Athletes Fibrosis and sclerosis of conduction system Bundle Branch Blocks Both bundle branches blocked Results in AV block Form of HIS-Purkinje system disease ONE bundle branch blocked Does not cause AV block Normal PR interval QRS will be prolonged Sites of AV Block Disorder 1st Degree Mobitz I Mobitz Il 3rd degree (Complete) Pacemaker Common Site of Block AV node AV Node His-Purkinje System His-Purkinje System Treatment for "high grade" AVblock Usually 3rd degree or Mobitz Il Often in patients with symptoms (syncope, dizziness) Right Bundle Branch Block 72
Left Bundle Branch Block Bundle Branch Blocks • Symptoms: None Identified incidentally on ECG May progress to AVblock (need for pacemaker) • Interfere with detection of ischemia ST elevations, T-wave inversions can be normal Bundle Branch Blocks Right bundle branch block characteristics vs rsR• qRs Left bundle branch block characteristics A. Rad/Wi kiped ia Bundle Branch Blocks Causes Often caused by slowly progressive fibrosis/sclerosis More common in older patients Can result from "structural heart disease" LBBB: Prior MI, cardiomyopathy RBBB: Right heartfailure 73
Atrial Fibrillation Cardiac arrhythmia Results in an irregularly, irregular pulse Atrial Fibrillation and Flutter Jason Ryan, MD, MPH Atrial Fibrillation J. Heuser/Wikipedia Atrial Fibrillation Diagnosis: EKG Atrial Fibrillation Atrial Fibrillation His RBB 74 LBB Purkinje Fi bers
Atrial Fibrillation Terminology Paroxysmal Comes and goes; spontaneous conversion to sinus rhythm Persistent Lasts days/weeks; often requires cardioversion Permanent Cardiomyopathy Caused by untreated, rapid atrial fibrillation "Tachycardia-induced cardiomyopathy" • LLVEF Systolic heart failure Preload Atrial fibrillation eliminates ventricular pre-filling • "Loss of atrial kick" Decreases preload Can lead to low cardiac output and hypotension Especially in "preload dependent" patients Aortic stenosis LVH or diastolic heart failure (stiff ventricle) Atrial Fibrillation Symptoms Wide spectrum ofsymptoms Asymptomatic Heart Rate 100bpm AV node refractory period determines heart rate Young, healthy patients -5 rapid heart rate Older patients slower heartrate Atrial rate in fibrillation: 300-500bpm Ventricular rate: 70-180bpm Atrial Fibrillation Thrombus in Left Atrial Appendage 75
Atrial Fibrillation Cardiac Embolism Brain (stroke) Gut (mesenteric ischemia) Spleen Con structio n Dea I Mkti ng Atrial Fibrillation Risk Factors Age • —10% of patients >80
Rate Control Beta Blockers Calcium Channel Blockers Digoxin Rhythm Control Goal: restore sinus rhythm Cardioversion Cardioversion Chemical Administration of antiarrhythmic medication Often Ibutilide (class Ill antiarrhythmic) Less commonly used due to drug toxicity Rate Control Use drugs that slow AV node conduction Beta blockers Usually ßl selective agents Metoprolol, Atenolol Calcium channel blockers Verapamil, Diltiazem Digoxin Increases parasympathetic tone to heart Cardioversion Electrical Deliver "synchronized" shock at time of QRS Administer anesthesia Deliver electrical shock to chest All myocytes depolarize Usually sinus node first to repolarize/depolarize Pollo/Wikipedia Cardioversion Spontaneous Often occurs after hours/days 77
Cardioversion Risk of Stroke Chemical/electrical cardioversion may cause stroke 48hours required for thrombus formation Symptoms 48hours (or unsure) Anti-coagulation 3 weeks -Y cardioversion Transesophageal echocardiogram to exclude thrombus Exception: Hypotension/shock Emergent cardioversion performed Anticoagulation Warfarin Requires regular INR monitoring Goal INR usually 2-3 Rivaroxaban, Apixaban Factor X inhibitors Dabigatran Direct thrombin inhibitor Aspirin Less effective Only used if risk of stroke is very low Less risk of bleeding Stroke Risk CHADS Score CHF (1 point) HTN (1 point) Age >75yrs (1 point) Diabetes (1 point) Stroke (2 points) Score 22 = Warfarin or other anticoagulant Score 0-1 = Aspirin Rhythm Control Antiarrhythmic medications Administered before/after cardioversion Class I drugs Flecainide,propafenone Class Ill drugs Amiodarone, sotalol, dofetilide Anticoagulation Whether atrial fibrillation persists or sinus rhythm restored anticoagulation MUST be administered Studies show similar stroke risk for rate control versus rhythm control Stroke Risk CHADS VASC Score CHF (1 point) HTN (Ipont) Diabetes (1 point) Stroke (2points) Female (1 point) Age 65-75 (1 point) Age >75yrs (2points) Vascular disease (Ipoint) Score 22 = Warfarin or other anticoagulant Score 0-1 = Aspirin 78
Atrial Fibrillation Summary New Onset Atrial Fibrillation Emergent Cardioversion Echocardiogram TSH Rate Control Beta Blockers Calcium Blockers Digoxin Rhythm Control Anticoa lation Aspirin Warfarin Other drugs Cardioversion Antiarrhythmic drugs Pulmonary Vein Isolation Surgical Therapy for Atrial Fibrillation i; Atrial Flutter Pulmonary Vein Isolation Surgical Therapy for Atrial Fibrillation Atrial Flutter Atrial Flutter Symptoms Generally the same as atrial fibrillation May be asymptomatic Palpitations, dyspnea, fatigue 79
Atrial Flutter Treatment Generally the same as atrial fibrillation Rate or rhythm control Rate-slowing drugs Cardioversion Anticoagulation based on stroke risk Atrial Flutter Ablation 80
AVNRT Jason Ryan, MD, MPH PSVT Paroxysmal Supraventricular Tachycardia Often causes sudden-onset palpitations Chest discomfort Rarely syncope VI Normal Conduction LBB PSVT Paroxysmal Supraventricular Tachycardia • Intermittent tachycardia (HR > 100bpm) Sudden onset/offset Contrast with sinus tachycardia Electrical activity originates above ventricle "Supraventriculaff' Contrast with ventricular tachycardia Produces narrow QRS complex (
Dual Pathways PAC Slow Conduction Short RP AVNRT Fast Conduction Long RP HIS Retrograde P Waves Carotid Massage Examiner presses on neck near carotid sinus Stretch ofbaroreceptors CNS response as if high blood pressure Recurrent episodes of palpitations Many episodes spontaneouslyresolve conduction in AV node breaks arrhythmia Will halt conduction is slow pathway Carotid massage Vagal maneuvers Adenosine Vagal Maneuvers Valsalva Patient bears down as if moving bowels Increased thoracic pressure Aortic pressure rises heart rate and AV conduction Breath holding Coughing Deep respirations Gagging Swallowing • Increased vagal tone U AV node conduction AVNRT Chronic Treatment Many patients need no therapy Beta blockers, Verapamil/Diltiazem Slow conduction in slow pathway Surgical ablation of slow pathway 82 Wikipedia/Public Domain
Wolff-Parkinson White Jason Ryan, MD, MPH EKG in WPW Short PR Delta Wave Cardiac Electrical System WPW Syndrome Wolff-Parkinson White Syndrome Cardiac electrical disorder • "Accessory atrioventricular pathway" Conducts impulses from atria to ventricles Bypasses AV node "Bundle of Kent" Ventricular depolarization before AVnodal impulse May lead to arrhythmias WPW EKG SA His RBB LBB Purkinje Fibers AVRT AV Re-entrant Tachycardia Orthodromic 83 Antidromic
Bypass Tract Consequences Most patients asymptomatic EKG with delta wave only Called WPW "pattern" Some have tachycardias Presents as palpitations Called WPW syndrome AVRT (anti or orthodromic) Rarely causes syncope or sudden death Treatment: Ablation of accessory pathway Atrial Fibrillation in WPW Slowing AV node conduction is dangerous Allows more impulses over bypass tract Usual atrial fibrillation therapies contraindicated Beta blockers Calcium channel blockers Digoxin Adenosine Acute treatment: Cardioversion or antiarrhythmics Ibutilide, procainamide Slow conduction in bypass tract Atrial Fibrillation in WPW Atrial fibrillation can be life threatening Atrial depolarization rate 300-500/min AVnode conducts
Vaughan Williams Antiarrhythmic Drugs Jason Ryan, MD, MPH Use of Antiarrhythmic Drugs Drugs used to "suppress" arrhythmias Prevent formation of aberrant impulses Most also cause arrhythmias Can lead to cardiac arrest and death Used in dangerous arrhythmias Also used in recurrent symptomatic arrhythmias Mechanisms All drugs slow cardiac electrical activity Class I drugs Block Na channel Class Ill drugs -5 Block K channels Class Il, IV: Slow sinus and AV node conduction Class I Quinidine Procainamide Lidocaine Mexiletine Flecainide Propafenone Class 111 Amiodarone Sotalol Dofetilide Ibutilide la 1b Ic Class 11 Beta Blockers Class IV Ca-channel Blockers (Verapamil/Diltiazem) Use of Antiarrhythmic Drugs Persistent/recurrent ventricular tachycardia Recurrent atrial fibrillation Ventricular Tachycardia Rapid Atrial Fibrillation Myocyte Action Potential Atrial/ventricular myocytes Class 1 Ill BB, CCB (Class 11. IV) Phase 1 K+ (out) Omv Phase 0 Na+ (in) -85mv Phase 2 (out) Ca+ (in) Phase 3 K+ (out) Phase 4 85
Na Channel Blockade Slow Phase 0 Prolong QRS Myocyte Action Potential Atrial/ventricular myocytes Omv ERP -85mv AP Class I drugs Effects on Resång Action Potenåal la TQRS TQT TAP TERP 1b +/-QRS QT IAP ERP Ic QRS +/-QT K Channel Blockade Prolonged Repolarization Prolong QT Class I drugs Block sodium channels -5 prolongQRS Some also affect K+ channels prolong Qt Can prolong action potential duration Can prolong effective refractoryperiod Class la Drugs Quinidine, procainamide Prolong QRS • Can also prolong Qt (UK + outflow) Quinidine Oral drug Can decrease recurrence rate of atrial fibrillation Associated with increased mortality Procainamide Intravenous drug Slows conduction in accessory pathways (WPW) Used in arrhythmias associated with bypass tracts 86
Procainamide Associated with drug-induced lupus Classic drugs: INH, hydralazine, procainamide Often rash, arthritis, anemia Antinuclear antibody (ANA) can be positive Key features: anti-histone antibodies Resolves on stopping the drug Pixabay/ Publi c Doma in Class 1b Drugs Lidocaine, Mexiletine Most Na channel binding in depolarized state • Ischemia more depolarized myocytes Effective drugs in ischemic arrhythmias Most Na channel block here (depolarized state) Omv ERP -85mv Phase 4 Class 1b Drugs Lidocaine, Mexiletine Lidocaine also a local anesthetic Na channel nerve block May cause CNS stimulation Tremor, agitation Tremor in patient on Mexiletine = toxicity Cardiovascular side effects From excessive block of Na channels Bradycardia, heart block, hypotension Class 1b Drugs Lidocaine, Mexiletine Little/no effect on QRS at normal HR Slight decrease in Qt interval (minimal) Least effect on action potential of class 1 drugs Class 1b Drugs Lidocaine, Mexiletine Drug rapidly unbinds Slow heart rates: little drug effect by next heart beat More effective in fast heart rates Less time to unbind before Na channels open again Main use: ischemic ventricular tachycardia Fast heart rates Depolarized Na channels Class Ic Drugs Flecainide, Propafenone Block open Na channels Very slow unbinding Result: QRS can markedly prolong Limited use due to concern of toxicity Especially proarrhythmic effects 87
CAST Trial The Cardiac Arrhythmia Suppression Trial Landmark clinical trial of antiarrhythmic drugs Tested the suppression hypothesis Suppression of arrhythmias with drugs is a good thing Patients with asymptomatic arrhythmias after MI Encainide and flecainide administered Patients taking drugs had less arrhythmias Also: 3.6-fold increased risk of arrhythmic death Result: Major antiarrhythmic drugs Now used only with compelling indication Use Dependence Na channels fluctuate between 3 different states Resting, Open and Inactivated Drugs bind more in certain states Class I drugs bind best in open/inactivate states States when Na channel is in "use" These drug exhibit "use dependence" n active Resting Use Dependence Use dependent drugs: more binding fast heart rates All class I drugs have some use dependence Seen most frequently IC drugs Practical implication: Flecainide and propafenone (IC drugs) Marked use dependence Toxicity (QRS prolongation) at high heart rates Stress testing often done to screen for toxicity Class Ic Drugs Flecainide, Propafenone Only used in patients with structurally normal hearts Effective in reducing recurrence of atrial fibrillation Must monitor for QRS prolongation Prolonged QRS Risk of cardiac arrest Use Dependence 3 Seconds Na Channels Open/ Inactive Bradycardia 3 Seconds Tachycardia Na Channels Resting Class Ill drugs Amiodarone, Sotalol, Dofetilide, Ibutilide Delayed Repolarization K+ Channel Blockade +/-QRS TQT TAP TERP 88
Torsade de Pointes Feared outcome of Qt prolongation Results in cardiac arrest Class IA, Ill drugs prolong Qt Amiodarone Highly lipid soluble IA Accumulates in liver, lungs, skin, other tissues Half-life about 58 days Once steady state reached, very long washout Safe in renal disease (biliaryexcretion) Amiodarone Side Effects Hyper and hypothyroidism Contains iodine • Increased LFTs Usually asymptomatic and mild Drug stopped if elevation is marked Skin sensitivity to sun Patients easily sunburn o o Wikipedia/ Public Domain Amiodarone Class Ill drug K channel blocker: Prolongs Qt interval Lowest incidence T DP of all class Ills Also has class I, Il, and IV effects Class I: Prolongs QRS Class Il, IV: Slow HR, delay AV conduction Very effective drug Suppresses atrial fibrillation Suppresses ventricular tachycardia Amiodarone Many potential side effects related to accumulation Less likely at lower dosages Risk accumulates over time Young patients on indefinite therapy at greatest risk Often used in older patients Amiodarone Side Effects Blue-gray discoloration Less common skin reaction 'Blue man syndrome" Most prominent on face Corneal deposits Secretion of amiodarone by lacrimal glands Accumulation on corneal surface Appearance of "cat whiskers" on cornea Does not usually cause vision problems See in many patients on chronic therapy 89
Amiodarone Side Effects Pulmonaryfibrosis Most common cause of death from amiodarone Foamy macrophages seen in air spaces Filled with amiodarone and phospholipids • "Honeycombing ' pattern on chestx-ray Sotalol and Dofetilide Both drugs block K channels (class Ill) Can prolong Qt interval torsade de pointes Practical consideration: Patients often admitted to hospital to start therapy Rhythm monitored on telemetry Qt segment checked by EKG each day Sotalol: Also has beta blocking properties Can be used in patients with cardiomyopathy "Reverse use dependence" Reverse Use Dependence 3 Seconds K Channels Open/ Inactive K Channels Resting Bradycardia 3 Seconds Tachycardia Amiodarone Side Effects When starting amiodarone Chest X-ray Pulmonary function tests (PFTs) Thyroid function tests (TFTs) Liver function tests (LFTs) Reverse Use Dependence K channels also fluctuate between 3 different states Class Ill drugs bind best in resting state These drug exhibit "reverse use dependence" Sotalol and Dofetilide Reverse use dependence: more binding slowrates Practical implication: Bradycardia in patient on sotalol/dofetilide Qt interval may prolong Increased risk oftorsade de pointes 90
Sotalol and Dofetilide Commonly used in patients with atrial fibrillation Typical case Recurrent episodes symptomatic atrial fibrillation Sotalol/Dofetilide started Cardioversion to restore sinus rhythm Sinus rhythm persists on therapy Other antiarrhythmic also used in this manner Amiodarone Propafenone Flecainide Cardioversion Termination ofarrhythmias Ibutilide Intravenous drug Half life of 2 to 12 hours Used for "chemical cardioversion" Beta Blockers Class Il Antiarrhythmics Main effect: Pacemaker cells (SA and AVnode) Decrease slope of phase 4 Prolong repolarization (phase 3) Often atrial fibrillation or flutter Electrical Cardioversion Requires sedation Beta Blockers Class Il Antiarrhythmics Ibutilide No sedation May cause Torsade IHR ICond Velocity TPR Interval Omv Phase 0 Ca Threshold Phase 3 -40mv -85mv Phase 4 Calcium Channel Blockers Verapamil and Diltiazem Block calcium channels Slow heart rate Slow AV node conduction Omv Phase 0 Ca Threshold Phase 3 -40mv -85mv 91 Phase 4 f (Na)
Calcium Channel Blockers Verapamil and Diltiazem Normal Ca Blocker Decreased Slope Slower Rise Atrial Fibrillation LHR ICond Velocity TPR Interval Beta blockers and CCBs commonly used Control ventricular rate Atrial Fi brillation with rapid ventricular response Rate controlled with beta blocker or CCB Adenosine Nucleoside base Used to make ATP Receptors in many locations (purinergic receptors) AV nodal tissue Vascular smooth muscle Adenosine Triphosphate AV Block Beta blockers/Ca channel blockers -5 AV conduction Type 1 AV block Wenckebach (Mobitz I) Sudden Cardiac Death • Increased risk among systolic heart failure patients Lower rates among patients on beta blockers • Improved mortality Ventricular Tachycardia Ventri cular Fi brillation Adenosine AV nodal cells: Activates K+ channels Drives K+ out of cells Hyperpolarizes cells: Takes longer to depolarize Also blocks Ca influx Res ult: Slowing of conduction through AVnode 92
Adenosine Short half life Given IV for acute therapy ofSVT Slows AV node conduction Narrow Complex Originates above HIS bundle Adenosine Effects blocked by theophylline and caffeine Block adenosine receptors NH2 Adenosine Magnesium P-13 Caffeine o NH Theophylline Acute management of torsade de pointes Mg blocks influx of Ca into cells Ca influx leads to early afterdepolarizations Phase 1 K+ (out) Phase 2 Ca+ (in) K+ (out) Omv 0 mv Phase 3 Phase 0 K+ (out) Na+ (in) ERP -85mv Phase 4 Adenosine Most common SVT: AVNRT AVnode reentrant tachycardia Slow and fast circuits in AV node -5 arrhythmia Adenosine slows AVnode conduction Arrhythmia with terminate Adenosine Adenosine Also a vasodilator Causes skin flushing, hypotension Some patients also develop dyspnea, chest pain Effects quickly resolve Must warn patients before administration for SVT Jorge Gonzålez/Flikr Atropine Muscarinic receptor antagonist Parasympathetic block* t HR and AV conduction Used in bradycardia t heartrate Also speeds conduction through AV node Useful for bradycardia especially from AVblock 93
Atropine Before Atropine After Atropine Digoxin Two cardiac effects #1: Increases contractility Used in systolic heart failure with LVEF #2: Slows AVnode conduction Used in atrial fibrillation to slow ventricular rate Digoxin AV Nodal Slowing Suppresses AV node conduction Increased vagal (parasympathetic) tone Separate effect from blockade of Na-K-ATPase Can be used to heart rate in rapid atrial fibrillation Continued atrial fibrillation Fewer impulses to ventricle —Y slower heart rate Effects similar to BB and CCB in AVnode Atropine May side effects related to muscarinic block Toxicity: Dry mouth Constipation Urinary retention Confusion (elderly) Digoxin Increased Contractility • Inhibits Na-K-ATPase DIGOXIN o Digoxin Na trapped inside ofcell Less Na exchange for Ca (pump 2) Result: More Ca inside ofcell Digoxin Toxicity Renal clearance Risk of toxicity in patients with chronic kidney disease Hypokalemia promotes toxicity Caused by many diuretics, especially loop diuretics Digoxin patient on furosemide -5 toxicity Levels often need to bemonitored 94
Digoxin Toxicity Gastrointestinal Anorexia, abdominal pain Neurologic Lethargy, fatigue Delirium, confusion, disorientation Weakness Visual changes Alterations in color vision, scotomas Cardiac arrhythmias Digoxin Toxicity Treatment Digibind Digoxin Toxicity Cardiac Toxicity More Na inside of cell t resting potential atrial/ventricular cells Increased automaticity Dig toxic rhythms: Extra beats: atrial, junctional, ventricular Evidence of AV node block blindness Digoxin antigen binding fragments (Fab) Produced in animals (sheep) Dig bound to albumin (hapten) —Y antibodies Antibody converted to fragments Corrects hyperkalemia,symptoms
Heart Murmurs Jason Ryan, MD, MPH Laminar vs. Turbulent Flow Laminar Flow = Quiet(er) Turbulent Flow = Loud High Flow Rates Narrow Flow Areas Murmurs Other Descriptors Heart Murmurs Cardiac sound heard with stethoscope Caused by turbulent blood flow May be normal or pathologic Wikipedia/PubIic Domain Murmurs Grading • I - barely audible on listening carefully • Il - faint but easily audible loud and easily audible, no thrill • Ill- • IV - loud murmur with a thrill V -heard with scope barely touching chest VI - audible with scope not touching the chest LUSB Pulmonic Murmurs Systole Holosystolic Pansystolic Diastole Crescendo Systole Decrescendo Murmurs Location RUSB Aortic Stenosis LSB Aortic Regurg HCM M PDA A ex Mitral Murmurs Crescendo- decrescendo LLSB Tricuspid Murmurs VSD 96
Murmurs Location Point of maximal impulse (apical impulse) Left 5th intercostal space Mid-clavicularline Lateral shift = Enlarged heart Hyperdynamic Base Systolic Murmurs Occur when heart contracts/squeezes Between Sl-S2 Aortic stenosis Mitral regurgitation Pulmonic stenosis Tricuspid regurgitation Hypertrophic cardiomyopathy Ventricular septal defect (VSD) Aortic Stenosis Murmur Systolic crescendo -decrescendo murmur Also called an "ejection murmur" Apex Innocent/ Functional Murmurs Caused by normal flow of blood Common in children Also young, thin patients Generally soft murmurs No signs/symptoms of heartdisease Stills murmur Pulmonic flow murmur Venous hum Diastolic Murmurs Occur when heart relaxes/fills Between S2-S1 Aortic regurgitation Mitral stenosis Pulmonic regurgitation Tricuspid stenosis Aortic Stenosis Severe Disease Findings Late-peaking murmur Slow flow across stenotic valve Soft/quiet S2 Stiff valve can't slam shut Pulsus parvus et tardus Weak and small carotid pulses Delayed carotid upstroke 97
HCM Hypertrophic Cardiomyopathy Same murmur as aortic stenosis Differentiated bymaneuvers Valsalva Decreases venous return/preload Increase HCM murmur Decrease AS murmur HCM Mitral Regurgitation Holosystolic murmur heard best at the apex 5thintercostal space, mid-clavicular line Holosystolic (Pansystolic) Apex Mitral Stenosis No left sided S3, S4 in mitral stenosis Time to opening snap associated with severity High left atrial pressure in severe disease Higher left atrial pressure time to opening snap Short time to opening snap seen in severe disease Aortic Regurgitation Murmur Decrescendo, blowing diastolic murmur Mitral Stenosis Diastolic rumbling murmur Preceded by opening snap Systole Diastole Systole Diastole Diastolic Rumble os (Murmur) Tricuspid/ Pulmonic Disease Valve lesions sound like left sided-counterparts Heard in differentlocations Left upper sternal border Pulmonic stenosis/regurgitation Left lower sternal border Tricuspid stenosis/regurgitation 98
Carvallo's Sign Most right sided murmurs louder with inspiration • Inspiration draws blood volume to lungs Louder right sided murmurs Softer left sided murmurs rlght sided murmurs increase with Inspiration IEft sided murmurs increase with Exhalation PDA Patent Ductus Arteriosus Continuous, "machine-like" murmur I I Ill Ill I Maneuvers Preload/ Venous Return Increase preload/venous return Leg raise - blood falls back toward heart Squatting - blood in legs forced back toward heart Decrease preload/venous return Valsalva- t intra-thoracic pressure* vein compression -51 VR Standing - Blood falls toward feet, away from heart Most murmurs INCREASE with more preload except: HCM MVP VSD Ventricular Septal Defect Holosystolic murmur similar to MR Small VSD -5 more turbulence loud murmur 3 Causes Holosytolic Murmurs Mitral Regurgitation Tricuspid Regurgitation VSD Holosystolic (Pansystolic) Maneuvers Performed at bedside with patient May increase or decrease murmur Used to make diagnosis 75 45 30 Davidjr74/Wikipedia Valsalva Maneuver Bear down as if moving bowels Phase I (few seconds) t thoracic pressure venous return (compression of veins TRA pressure) Transient rise in aortic pressure (compression) heart rate and AVnode conduction (baroreceptors) Phase Il L preload -5 L cardiac output t heart rate and AV node conduction (baroreceptors) 99
Maneuvers Afterload • Increase Afterload Hand grip - clench fist Decrease Afterload Amyl Nitrate - vasodilator CH3 H3C Amyl Nitrate Clues to Diagnosis Young female, otherwise healthy MVP Healthy, young athlete, syncope -5 HCM • Immigrant or pregnant Mitral stenosis • IV drug abuser Tricuspid regurgitation Turner Syndrome or Aortic Coarctation Bicuspid AV Early stenosis Aortic regurgitation Marfan -5 MVP o o Maneuvers Afterload Backward Valve Disorders AR, MR, VSD Louder with more afterload More force pushing blood backward Forward Valve Disorders MS, AS Softer with more afterload Less pressure difference moving blood forward MVP, HCM Softer Increased LVcavity size Summary Commonly Tested Murmurs AS/HCM MR/VSD AR MS PDA 100 Il Il Ill
Heart Sounds Jason Ryan, MD, MPH Sl and S2 Normal heart sounds Each has two components One from left sided valves (aortic, mitral) One from right sided valves (tricuspid, pulmonic) Sl usually "single" Two components close together Cannot distinguish separate sounds S2 can be "split" Two components far enough apart to be audible Physiologic S2 splitting The Cardiac Cycle Aorta LV LV Volume Heart Sounds Venous Sl and S2 Mitral and tricuspid valves close Aortic and pulmonary valves close MV TV AV PV MV TV AV PV Persistent S2 splitting RBBB or Pulmonary Hypertension Exhalation MV TV Inspirati on PeRsistent = Right sided delay AVPV AV Exhalation Inspiration MV TV MV TV AV PV AV PV Increased venous return delays P2 by 40-60ms Single to split with inspiration Delayed PV closure even during exhalation 101
Fixed S2 splitting Atrial septal defect Paradoxical S2 splitting Delayed closure of aortic valve Atrial-SeptaLD.efe.cLEixed split S2 Systolic Ejection Murmur LSB Exhalation Inspiration MV TV MV TV AV PV AV Exhalation MV TV Inspiration MV TV PV AV PV AV Flow across ASD -5 increased right sided flow Paradoxical Splitting Electrical causes -5 delayed LVactivation LBBB RV pacing Mechanical causes delayed LVoutflow LV systolic failure Aortic stenosis Hypertrophic cardiomyopathy ParodoxicaL = Left sided delay Cardiac Phonography tutuwguu ,lnjmntnlf Fixed Split S2 Summary of S2 Splitting Physiologic = normal respiratory variation PeRsistent = RBBB, pulmonary HTN Fixed = Atrial septal defect ParadoxicaL = LBBB, cardiomyopathy Loud P2 Loud pulmonic component of S2 Pulmonary hypertension Forceful closure of pulmonary valve Normally P2 not heard at apex If you hear it here, it's "loud" 102
S3 and S4 Pathologic/abnormal heart sounds Occur in diastole during filling of left ventricle Low-pitched sounds heard best with bell S3: Early fillingsound S4: Late filling sound Tama988 /Wikipedi a Low frequency best heard with bell Louder in left lateral decubitus position Loudest at apex Rama/W ikipedia Right Sided S3 & S4 Both sounds can occur in right ventricle Same mechanisms as left sounds Right heart failure right sided S3 Right ventricular hypertrophy right sidedS4 Commonly seen in acute heart failure High LA pressure rapid early filling of S3 Associated with T LAP & TLVEDP "Pushers" push blood into LV Very specific sign of high left atrial pressure May be heard in normal hearts Young patients (
Mitral Valve Prolapse Billowing of mitral valve leaflets above annulus Common cause of mitral regurgitation Causes a systolic click Don't confuse with opening snap of mitral stenosis Mitral Valve Disorders Proclick Stenosnap Mitral Valve Prolapse Systole Click Murmur 104 Diastole Normal MVP
Heart Failure Basics Jason Ryan, MD, MPH Heart Failure H20 Tank Pump Heart Failure H20 Tank Pump Heart Failure • Impaired ability of the heart to pump blood Hallmark: Low cardiac output J co Heart Failure H20 Tank Pump Heart Failure H20 Tank Heart 105
Heart Failure Lungs Veins Heart Heart Failure Pathophysiology Left ventricular failure -5 tLVpressure LVsystolic pressure: depends on contractility (can be low) LVEDP = always high in left heart failure Hallmark of left heart failure Less blood pumped out -Y more left behind more pressure Stiff ventricle (diastolic HF) -5 high pressure Heart Failure Pathophysiology • "Failing ' chambers Increased pressures Pressures rise in cardiac chambers Heart Failure Pathophysiology t LVEDP t LA pressure t pulmonary capillary pressure Dyspnea Pulmonary edema Aorta LV 106
Heart Failure Pathophysiology TPc Heart Failure Signs/Symptoms Physiologic effects of lying flat (supine) Increased venous return Redistribution of blood volume From lower extremities and splanchnic beds to lungs Little effect in normal individuals Impaired ventricle cannot tolerate changes Worsens pulmonary congestion and breathing Heart Failure Right Heart Failure Most common cause R heart failure: Left heart failure Occasionally right heart failure occurs in isolation Normal left atrial pressure High pulmonary artery, right ventricular, right atrial pressure Usually secondary to a lung process Pulmonary hypertension COPD This is often called "cor pulmonale" Heart Failure Pathophysiology t pulmonary capillary pressure -5 t PApressure t PA pressure t RVpressure t RV pressure t RApressure Right atrial pressure = central venous pressure High pressure in venous system t jugular venous pressure (neck veins) Capillary leak pitting edema Heart Failure Signs/Symptoms Left heart failure Dyspnea especially on exertion Paroxysmal nocturnal dyspnea (wake up SOB) Orthopnea (can't breathe lying flat) Right heart failure Increased jugular venous pressure Lower extremity edema Liver congestion (rarely can cause cirrhosis) "Backward failure" Heart Failure Signs/Symptoms Low flow signs/symptoms ("forward failure") Loss of appetite Weight loss (cachexia) Confusion Cool extremities "Narrow pulse pressure" Seen only with very low cardiac output (systolic HF) Not seen in diastolic heart failure 107
Heart Failure Lung Findings Classic finding is rales Fluid filled alveoli "pop" open with inspiration Chest X-ray shows congestion Lungs/CXR can be clear in chronic heart failure Tlymphatic drainage Heart Failure Signs/Symptoms Elevated jugular venous pressure (normal 6-8cmH20) Look for height of double bounce (cause by a and v waves) Heart Failure Signs/Symptoms Lower extremity pitting edema • Increased capillary hydrostatic pressure Fluid leak from capillaries -5 tissues Gravity pulls fluid to lower extremities TPc James Heilman, MD Heart Failure Lung Findings Heart failure cells Hemosiderin (iron) laden macrophages Brown pigment in macrophages Zorkun/Wiki pedia Heart Failure Hepatojugular Reflux Pressure on abdomen raises JVP 1-3cm normally With failing RV, increase is greater Heart Failure Abnormal Heart Sounds S3 (associated with high left atrial pressure) S4 (associated with stiff left ventricle) Displaced apical impulse - enlarged heart 108
Heart Failure Pathophysiology All forms of heart failure lead to cardiac output Activates two physiologicsystems Activation of sympathetic nervous system Activation of renin-angiotensin-aldosterone system All RAAS hormone levels will rise Both systems lead to two key effects: Increased peripheral vascular resistance (vasoconstriction) Retention of sodium/water (kidneys) Heart Failure Sodium/ Water Retention cardiac output Effective Circulating Volume TRAAS t SNS t ADH t Na/H20 t Total Body Water Heart Failure Other Hormones ANP released by atrial myocytes BNP (brain natriuretic peptide): Ventricles Both rise with volume/ pressure overload Both counter effects of RAAS system BNP sometimes used for diagnosis indyspnea High levels suggest heart failure Low levels suggest other causes of dyspnea ANP/BNP RAAS Heart Failure Total Peripheral Resistance Cardiac output falls vasoconstriction Angiotensin Il, sympathetic nervous system TPR always high Blood pressure often high but may be low Depends on combined changes CO and TPR BP = CO X TPR Heart Failure Other Hormones ANP (Atrial natriuretic peptide) Atrial stretch (pressure/volume) -5 ANP release Vasodilator (LTPR) Constricts renal efferents/dilates afferents t diuresis Opposite effects of RAASsystem Afferent Nesiritide Recombinant BNP Vasodilation L afterload, tCO Efferent Failed to show benefit in clinical trials 109
Heart Failure Diagnosis Most common: typical signs/symptoms Elevated BNP level Heart catheterization Increased LVEDP = left heart congestion/failure Increased RA, RVEDP = right heart congestion/failure Pulmonary ry Catheter BruceBlaus 110
Systolic and Diastolic Heart Failure Jason Ryan, MD, MPH Heart Failure Systolic and Diastolic Same congestive signs/symptoms Dyspnea, orthopnea, paroxysmal nocturnal dyspnea Rales, T JVP, pitting edema Exception: Low flow symptoms insystolic only Cool extremities Cachexia Confusion Concentric Hypertrophy Pressure overload Chronic Tt pressure in ventricle: H TN, Aortic stenosis Decreased compliance (stiff ventricle) Often seen in diastolic heart failure Heart Failure Systolic and Diastolic Systolic Heart Failure Ejection fraction is reduced Diastolic Heart Failure EF is normal (55-65%) Dilated Cardiomyopathy Systolic heart failure with LV cavity dilation • "Eccentric" hypertrophy Volume overload (chronic retention of fluid in cavity) Longer myocytes Sarcomeres added in series Normal LV Size LV Vol Systolic HeartFailure Contractility 111 Dilated LV Normal LV Size LV Size Increased myocyte size Sarcomeres in parall el Increased wall thickness Increased myocyte size Sarcomeres in series Normal wall thickness LVVol Diastolic Heart Failure LV Compliance Lusitropy
Systolic Heart Failure Cardiac output Problem in SYSTOLE Can't get blood out Stroke volume SV = EDV - ESV T t ESV (L contractility) T EDV (TESV+ VR) t LVEDP Frank-Starling Curve Normal U Contractility Stroke Volume LVV01 Systolic HeartFailure Contractility Diastolic Heart Failure Cardiac output Problem in DIASTOLE Can't get blood in Small stroke volume EDV (1 filling) • t t LVEDP (stiff ventricle) LVVol Diastolic Heart Failure LV Compliance Lusitropy Systolic Heart Failure Most common cause: Myocardial infarction Myocytes replaced by scar tissue "Ischemic" cardiomyopathy Many causes of "non-ischemid' cardiomyopathy About 50% idiopathic Many other causes: viral, familial, peri-partum, chemotherapy toxicity, HIV, alcoholic, sarcoidosis, tachycardia-mediated Preload (LVEDV) Systolic vs. Diastolic EDV ESV svvco 100 40 60 60 200 160 40 20 90 40 50 56 Diastolic Heart Failure Exact cause unknown Many cases have concentric hypertrophy Many associated conditions Age, diabetes, hypertension Terms: Heart fail ure preserved EF HFpEF Diastolicdysfunction 112
Nonischemic Cardiomyopathy Viral May follow upper respiratory infection Many associated viruses Coxsackie Influenza, adenovirus, others Virus enters myocytes Causes myocarditis -5 cardiomyopathy Myocarditis phase may go undiagnosed No specific therapy for virus Pixabay/ Public Domai n Nonischemic Cardiomyopathy Peri-partum Late in pregnancy or early post-pregnancy Exact cause unknown (likely multifactorial) Women often advised to avoid future pregnancy øyvind Holmstad/Wikipedia Nonischemic Cardiomyopathy Nonischemic Cardiomyopathy Chemotherapy Usually after treatment with anthracyclines Antitumor antibiotics Doxorubicin and daunorubicin Familial Mutations Often sarcomere proteins Beta myosin heavy chain Alpha myosin heavy chain Troponin Many autosomal dominant O OH O OH Daunorubicin O OH •tee. O O OH NH2 Doxorubicin (Adriamycin) Wikipedia/Public Domain Nonischemic Cardiomyopathy Tachycardia-mediated Constant, rapid heart rate forweeks/months Leads to depression of LVsystolicfunction Reversible with slower heartrate X-Iinked, autosomal recessive also descri bed Nonischemic Cardiomyopathy Takotsubo/Apical ballooning Stress-induced cardiomyopathy Occurs after severe emotional distress Markedly reduced LVEF • Increase CK, MB, Troponin; EKGchanges Looks like anterior MI (but no coronary disease) Usually recovers 4-6 weeks Jheuser/Wiki pe dia 113
Alcohol Chronic consumption can cause cardiomyopathy Believed to be due to toxic metabolites Can recover with cessation of alcohol Pixabay/ Publi c Domain High Output Heart Failure Heart in overdrive Severe anemia Thyroid disease John Liu/ Flikr Thiamine (Bl) vitamin deficiency (beriberi) A-V fistulas (post-surgical) Exact mechanism unclear Decreased LVfilling time Defining characteristic: HIGH cardiac output Heart failure symptoms in absence of low output TJVP, pulmonary edema 114
Restrictive Cardiomyopathy Jason Ryan, MD, MPH Restrictive Heart Disease LVEF = normal Left ventricular volume = normal (not dilated) Restricted filling = t atrial pressure Dilated left and right atria Classic imaging findings: Normal left ventricular function/size Bi-atrial enlargement Restrictive Heart Disease Classic signs Kussmaul's sign Inspiration causes rise in JVP Restrictive Heart Disease Something "infiltrates" the myocardium Granulomas (Sarcoid) Amyloid protein (Amyloidosis) Heart cannot relax and fill SEVERE diastolic dysfunction RESTRICTED AREA PUBLIC ACCESS M ark Buckawicki/W i ki pedia Restrictive Heart Disease Clinical Features Dyspnea Prominent right heart failure Markedly elevated jugular venous pressure Lower extremity edema Liver congestion May lead to cirrhosis ("nutmeg liver") David Mon niaux/Wikipedia Restrictive Heart Disease Rhythm Disturbances Myocardial infiltration may disrupt electrical activity Arrhythmias (sudden death) AV block Ventri cular Tachycardia 115 3rd Degree Heart Block
Restrictive Heart Disease Major Causes Amyloidosis Amyloid protein deposits in heart Various forms (primary, secondary, etc.) Ed Othman, MD Restrictive Heart Disease Major Causes Sarcoidosis Granuloma formation Usually involves lungs Extra-pulmonary organs include heart Restrictive Heart Disease Major Causes Hemochromatosis Iron excess Commonly causes dilated cardiomyopathy Rarely may cause restrictive Tomiha hndo rf Restrictive Heart Disease Classic signs Can see thickened myocardium Low voltage on EKG Classic finding in amyloidosis and Fabry's disease Restrictive Heart Disease Major Causes Fabry disease Lysosomal storage disease Deficiency of a-galactosidase A Accumulation of ceramide trihexoside Mediran/Wikip edia Restrictive Heart Disease Major Causes Post-radiation Acutely: May cause inflammation Fibroblast recruitment Extra-cellar matrix deposition Collagens and fibronectin Dina Wakulchik/Wikipedia 116
Restrictive Heart Disease Major Causes Pericarditis may occur acutely after therapy Long term effects Pericardial disease Coronary artery disease Valvular disease Conduction abnormalities Restrictive cardiomyopathy Fibrous tissue accumulation Diastolic dysfunction Restrictive Heart Disease Restrictive Heart Disease Major Causes Loeffler's syndrome Hypereosinophilic syndrome High eosinophil count Eosinophilic infiltration of organs Skin (eczema) Lungs (fibrosis) Bobjgalindo/Wikipedia Restrictive Heart Disease Major Causes Primary HES Neoplastic disorder Stem cell, myeloid, or eosinophilic neoplasm Secondary HES Reactive process Bo bjgalindo /Wikipedia Major Causes Eosinophilic infiltration ofmyocardium Common mode of death Acute phase Myocarditis (often asymptomatic) Chronic phase Bobjgalindo/Wikipedia Eosinophilic overproduction due to cytokines Occurs in parasitic infections (ascaris lumbricoides) Some tumors/lymphomas • Idiopathic HES Restrictive Heart Disease Major Causes Endocardial fibroelastosis Endocardial thickening (innermost myocardium) Infants in first year of life Thick myocardium Proliferation of fibrous (collagen) and elastic fibers Restrictive cardiomyopathy Avsar Aras Endomyocardial fibrosis and myocyte death Can see restrictive heart disease Thrombus formation common (embolic stroke) 117
Heart Failure Acute vs. Chronic Acute Congested/Swollen Pulmonary Edema Pitting Edema Chronic Euvolemic Clear lungs No pitting edema • JVP flat Acute Heart Failure Jason Ryan, MD, MPH Plasma Na = 140meq/L Acute Exacerbations Causes #1: Dietary indiscretion High salt intake #2: Poor medication compliance LukeB20161933/Wikipedia Dietary Indiscretion TNa Intake T Plasma Osmolarity TADH T Free Normal Plasma [Na] T Volume IRAAS CAD H T Urine Output Pixabay/Public Domain Acute Exacerbations Causes Infection/trauma/surgery Activation of sympathetic nervous system Ischemia (rare) Decreased cardiac output NSAIDs Inhibitcyclooxygenase (COX) -5 Uprostaglandins Prostaglandins maintain renal perfusion Result: Less renal perfusion -5 salt/water retention Acute Heart Failure Therapy Often treated in the hospital Goal: Symptom relief Contrast with chronic HF: reduce mortality/hospitalizations Often same therapies for diastolic versus systolic 118
Loop Diuretics 2C1 Ascendin Limb Loop Diuretics Metolazone Thiazide-like diuretic • Inhibits Na-CI reabsorption distal tubule Gives loop diuretics a "kick" Vigorous diuresis Side effects: additional fluid, K+ loss Nitrates Side effects Headache (meningeal vasodilation) Flushing Hypotension Wikipedia/Public Domain Loop Diuretics Furosemide, Bumetanide, Torsemide, Ethacrynic Acid • Inhibit Na-K-CI pump in ascending loop of Henle Result in salt-water excretion Relieve congestion • IV better than PO (gut is swollen) Key side effects Hypokalemia Volume depletion (Renal failure; hypotension) Sulfonamide drugs: allergy (except ethacrynic acid) Nitrates Predominant mechanism is venous dilation Bigger veins hold more blood Takes blood away from left ventricle Lowers LVEDV (preload), LA pressure Less pulmonary edema improved dyspnea Vasodilators "Afterload reduction" ACE inhibitors Hydralazine Cause peripheral vasodilation Reduced afterload -5 increased cardiac output 119
Nitrates plus Hydralazine Combination therapy for acute and chronic HF Studied in systolic heart failure Reduction in preload (nitrates) and afterload (hydralazine) Acute therapy: Improves symptoms Chronic therapy: Lowers mortality in some studies Largely replaced by ACE inhibitors Some studies suggested benefit in black patients Inotropes Milrinone Phosphodiesterase 3 inhibitor PD3 breaks down cAMP in myocyctes Inhibition tcAMP -Y contraction Vascular smooth muscle TcAMP (ß2) -5 dilation tlnotropy t Vasodilation Hypotension Contraction cAMP NU.., AMP Myocyte Inotropes Dopamine Does not cross blood brain barrier (no CNS effects) Peripheral effects highly dependent on dose Low dose: dopamine agonist Vasodilation in kidneys Medium dose: beta-I agonist Increased heart rate and contractility Inotropes Increase contractility Only for systolic heartfailure No role in diastolic heart failure (normal contractility) All activate 1 pathways in myocytes Increased HR and contractility Can also active pathways in smooth muscle Vasodilation hypotension Inotropes Dobutamine OH HO HO Mostly beta-I agonist Increases heart rate and contractility Weak beta-2 agonist Vasodilation Tlnotropy t Vasodilation Hypotension Similar effects to milrinone Contraction Inotropes Epinephrine HO x-U..- AMP Myocyte OH High dose: alpha agonist Vasoconstriction HO NH2 Also dose dependenteffects Low dose: beta-I and beta-2 agonist Increased heart rate & contractility, vasodilation High dose: alpha agonist Vasoconstriction 120
Inotrope Risks Numerous registries and clinical trials demonstrate increased mortality with routine use of inotropes Dangerous drugs used in very sick patients under monitored conditions A More Complex Heart Failure Course ER presentation: Dyspnea, edema, sleeping in chair Known LVEF Admitted to hospital Nitro drip to relieve dyspnea IV Furosemide to remove fluid Hospital Day 2 Poor urine output, Cool extremities, Cr rises 1.1+1.4 Dobutamine drip started Heart Failure Readmission Recurrence of HF after discharge common Post-discharge follow-up VERY important "Readmissions" a focus of public health policy High risk of readmission within 30 days Highest risk category among Medicare population A Typical Acute Heart Failure Course ER presentation: Dyspnea, edema, sleeping in chair Admitted to hospital Nitro drip to relieve dyspnea IV Furosemide to remove fluid Hospital Day 2 Weight down 4kg, feels better Nitro drip stopped Changed to oral furosemide Hospital Day 3: Discharge A More Complex Heart Failure Course Hospital Day 3-5 Good urine output Weight loss 4kg Breathing improves Hospital Day 6 Dobutamine stopped Furosemide drip stopped Hospital Day 7 Oral furosemide given Hospital Day 8: Discharge Acute Heart Failure Most patients require chronic, daily diuretic Helps to maintain euvolemic status Often oral furosemide or other loop diuretic Some patients require daily long acting nitrate Often oral isosorbide mononitrate 121
Acute Heart Failure Rare patients: continued treatment for low output Systolic heart failure only Chronic, IV infusion inotrope (i.e. "home dobutamine") Left ventricular assist device (LVAD) Heart transplant Digoxin Mechanism Two important cardiac effects #1: Inhibits Na-K-ATPase pump More Na in cell more Ca++ in cell More Ca++ more contractility #2 Suppresses AVnode conduction (parasympathetic) Can be used to slow heart rate in rapid atrial fibrillation Digoxin Benefits in Heart Failure Increased cardiac output • Improved symptoms and quality oflife No established mortality benefit Digoxin Only available oral inotrope "Dig and diuretic" once the mainstay of HF treatment What changed? Digoxin shown to have no mortality benefit Digoxin not effective for diastolic heart failure About 50% of all cases Digoxin carries significant risk of side effects Digoxin Benefits in Heart Failure Useful for systolic 1--1F patients Symptoms despite maximal therapy on other drugs i.e. persistent dyspnea despite good volume status Can be administered for acute heart failure Can be administered long term to maintain CO 122
Heart Failure Treatment Chronic Heart Failure Jason Ryan, MD, MPH Chronic Heart Failure LOTS of therapies for systolic heart failure Drugs: ACE-inhibitors, beta blockers, aldosterone antagonists Defibrillators Bi-ventricular pacemakers NO direct therapies for diastolic heart failure Guidelines recommendations: treat H TN, diabetes, A. fib Mainstay of therapy: monitor for symptoms, diuretics Renin-Angiotensin System ARBs Pathway Acute Heart Failure Rx Chronic Heart Failure Diastolic Heart Failure Symptom-Relief Loop diuretics Nitroglycerine Inotropes Systolic Heart Failure + Reni @ ACE @ ACE Inhibitors Net Result TSalt/Water Retention TPreload TTPR T Afterload Sympathetic System Renal Na/Cl resorption Arteriolar vas oconstri ction Adrenal aldosterone secretion Pituitary ADH secretion Systolic Heart Failure Chronic over-activation of two physiologic systems Renin-angiotensin-aldosterone system Sympathetic nervous system stimulation) Blockade -5 mortality and disease progression RAAS Drugs ACE Inhibitors Captopril, Enalapril, Lisinopril, Ramipril Block conversion Al All Angiotensin Receptor Blockers (ARBs) Candesartan, Irbesartan, Valsartan Directly block All receptor Both classes: morality, hospitalizations Side effects Hyperkalemia (laldosterone) Renal failure (IGFR) 123
ACE Inhibitors Unique Side Effects Due to increased bradykinin Dry Cough Occurs in —10% of patients Angioedema Swelling of face, tongue Can be life-threatening Beta Blockers Once contraindicated in systolic heart failure Negative inotropes Not used in acute heart failure May worsen cardiac output and symptoms Aldosterone Antagonists Bradykinin Bradykinin o Cough Vasodilation o Sympathetic System Renal Na/Cl resorption Arteriolar vasoconstriction Adrenal aldosterone secretion Pituitary ADH secretion o Spironolactone Eplerenone ACE Inhibitors A2 Inactive Metabolites Beta Blockers Three agents beneficial in chronic systolic HF failure Metoprolol (ßl) Carvedilol (ß1ß2a1) Bisoproplol (ßl) • morality, J hospitalizations Spironolactone, Eplerenone Potassium-sparing diuretics TNa/H20 excretion (diuretics) "Spare" potassium Unlike other diuretics, do not increase K* excretion HYPERkalemia is side effect Reduced mortality Reduced hospitalization rate 124
Spironolactone, Eplerenone Potassium-sparing diuretics Similar structure to testosterone Blocks testosterone effects Gynecomastia in men Eplerenone: No gynecomastia o Derivative of progesterone Activates progesterone receptors Amenorrhea in women Testosterone Spironolactone o o Eplerenone o Progesterone Neprilysin Inhibitors Sacubitril Entresto: oral combination sacubitril/valsartan Valsartan: angiotensin receptor blocker (ARB) • morality hospitalizations ANP/BNP RAAS Ivabradine Selective sinus node inhibitor Elevated HR worse prognosis Slows heart rate without contractility • Inhibits SA pacemaker "funny current" (If) Used in patients on max-dose beta blocker with THR Limited evidence of morality and Uhospitalizations •40mv -85mv Phase 4 Neprilysin Inhibitors Sacubitril Neprilysin: Degrades atrial/brain natriuretic peptide • Inhibition TANP/BNP Antagonists to RAAS system Vasodilatation Natriuresis (sodium excretion) Diuresis (water excretion) Reduced sympathetic tone ANP/BNP RAAS Neprilysin Inhibitors Side Effects Studied in combination with valsartan Many side effects similar to ARBs Hypotension Hyperkalemia Angioedema Rare, feared adverse effect Neprilysin also degrades bradykinin (like ACE) Angioedema may occur Cannot be given together with ACE inhibitors Chronic Systolic Heart Failure Drug Therapy ACE inhibitors/ ARB Beta Blockers Aldosterone antagonists Neprilysin inhibitors Ivabradine 125
ICD Implantable Cardiac Defibrillator Annual risk SCD >20% some studies Most due to ventricular tachycardia Biventricular Pacemakers Cardiac Resynchronization Therapy (CRT), BiV pacer ICD Implantable Cardiac Defibrillator Improve mortality in appropriate patients Implantation carries some risk: Bleeding, infection Inappropriate shocks Heart Failure Treatment Out of Synch After Pacemaker Pathway Diastolic Heart Failure No specific therapy 126 Acute Heart Failure Rx Chronic Heart Failure Lasix Nitroglycerine Inotropes Systolic Heart Failure Drugs ICD Bi-V Pacer
Cardiac Embryology Jason Ryan, MD, MPH Primitive Heart Primitive Heart 22 days Sinus Venosus Sinus Venosus Right Horn Smooth Truncus arteriosus Bulbus cordis Primitive ventricle Primitive atrium Left Horn 22 days Sinus Venosus Truncus arteriosus Bulbus cordis Aorta Pulmonary Artery Smooth LV/RV Trabeculated Primitive ventricle LV/RV Primitive Trabeculated Atria atrium Right Atrium Coronary Sinus OpenStax Colleg/Wi kipedia Cardinal Veins Form SVC/IVC (not from heart tube) Connect to right atrium Superior vena cava R common cardinal vein and R anterior cardinal Inferior vena cava Posterior veins vein Coronary Sinus Right Atrium (sinus venarum) OpenStax Colleg/Wikipedia Adult Heart Patrick J. Lynch, medical illustrator/Wikipedia 127
Primitive Heart 23 Aortk arch artene Truwus Left atrium Ventr& 35 days 24 days OpenStax Colleg/Wikipedia Ventricular Septum Formation Aorticopulmonary Septum Twist Membranous Endocardial Cushions Contribute to several cardiac structures Atrial septum Ventricular septum AVvalves (mitral/tricuspid) Semilunar valves (aortic/pulmonic) Endocardial cushion defects Atrioventricular canal defects Atrioventricular septal defects ASD, VSD, Valvular malformations Common in Down syndrome Endocardial Cushions Separate R/ L atria R/ L ventricle Cardiac Looping Heart tube "loops" at about 4 weeks gestation Establishes left-right orientation in chest Requires cilia and dynein Dextrocardia (heart on the right side of body) Seen in in Kartagener syndrome Part of primary ciliary dyskinesia Nevit/Wi kipedi a Ventricular Septum Pathology Membranous VSD (most common type) Muscular VSD Wikipedia/Public Domain Aorticopulmonary septum Spiral Septum Formed from neural crest cells Migrate to truncal and bulbar ridges Separates aorta and pulmonary arteries OpenStax Colleg/Wikipedia Fuses with interventricular septum Wikipedia/Public Domain 128
Aorticopulmonary septum Spiral Septum Abnormal formation -5 congenital pathology Transposition of greatvessels Failure to spiral Tetralogy of Fallot Skewed septum development Persistent truncus arteriosus Partial/incomplete septum development Atrial Septum Septum Prim um Endocardial Cushion Future Ventricles PFO Patent Foramen Ovale Found in —25% adults Septum Primum Future Ventricles Foramen Secundum Foramen Primum Atrial Septum Septum primum fuses Endocardial cushion Future Ventri cles Septum secundum grows Remaining Opening Foramen Ovale Future Ventri cles Failure of foramen ovale to close after birth Fetal Circulation High resistance to flow in lungs Oxygenated blood umbilical veins About 80% saturated (30mmHg 02) Travels directly to right atrium Bypasses liver via ductus venosus Bypasses lungs via foramenovale • Some blood gets to RV (SVC) Bypasses lungs via ductus arteriosus Left pulmonary artery to aorta Fetal Heart (een) Bruce Blaus/Wikipedia Septum primum/secundum fail to fuse Changes at Birth Pulmonary resistance falls More blood to left atrium LA pressure > RApressure Foramen ovale closes (fossa ovalis) Ductus arteriosus closes Fetal Heart Bruce Blaus/Wikipedia In utero: 02, t prostaglandins maintain patency Birth: t 02, prostaglandins (loss of placenta) PVR In Utero Birth 129
Changes at Birth Placenta has low resistance to flow • In utero: helps keep LA pressure low At birth: increase in peripheral resistance Rise in systemic blood pressure Rise in left ventricular pressure Contributes to rise in LApressure Placenta Wikipedia/Public Domain 130
w Shunts Jason Ryan, MD, MPH Shunts Left side pressures >> Right side pressures LA —10mmHg RA —6mmHg LV —120/10 RV —24/6 Ao 120/80 PA —24/12 Left to right connection -5 Left to rightflow VSD ASD (LA->RA) PDA (Aorta Left pulm artery) VSD Ventricular Septal Defect Most common congenital anomaly Communication LV/RV Harsh, holosystolic murmur Tricuspid area (LLSB) Wikipedia/Public Domain Shunts RV PA Shunts At birth: Left to right flow volume overload of right heart Blood flow to lungs unimpaired -Y no cyanosis YEARS later (untreated) Pulmonary vessels become stiff/thick Right ventricle hypertrophies Right sided pressures rise Shunt reverses (now R L) Cyanosis occurs (Eisenmenger syndrome) • "Blue kids" not "blue babies" VSD Ventricular Septal Defect Characterized in manyways Size Location Associated defects Wikipedia/Public Domain 131
VSD Ventricular Septal Defect • Small VSD Tiny hole resists flow across defect ("restrictive") Lots of turbulence —Y loud murmur Small shunt (small volume of flow across defect) Large VSD Large hole ("non-restrictive") Significant shunting Often closed surgically ASD Atrial Septal Defect • Oxygenated blood LA -5 RA t 02 saturation in RA, RV, PA • "Shunt run" Series of blood samples svc = 65% Ivc - — 65% ASD Atrial Septal Defect Foramen Ovale "Step up" Septum Secundum Too Short ART' Wikipedia/Public Domain Septum Primum Excessive Reabsorption Septum secundum Septum primum ASD Atrial Septal Defect Communication between left/right atrium Adds volume to RA/RV Delays closure of pulmonicvalve Wide, fixed splitting ofS2 Increased flow across P V/ TV Systolic ejection murmur Rarely a mid-diastolic murmur ASD Atrial Septal Defect Secundum type is most common Defects at site of foramen ovale/ostium secundum Poor growth of secundum septum Or excessive absorption of primum septum Located mid-septum Often isolated defect Foramen Ovale Septum secundum Septum primum ASD Afiial Septal Defect 132
ASD Atrial Septal Defect Primum type Defect at site of ostium primum Failure of primum septum to fuse with endocardial cushions Located near AVvalves; often occurs with other defects Seen in endocardial cushion defects (Down syndrome) Primitive Atria Ventricle PDA ASD Atrial Septal Defect PDA -4 Septum primum Endocardial cushion Primitive Atria Ventricle Patent Ductus Arteriosus Ductus arteriosus shunts blood in utero Left pulmonary artery aorta Closes close after birth "Functional" closure 18 to 24 hours (smooth muscle) "Anatomic" occlusion over next fewdays/weeks Becomes ligamentum arteriosum Patency maintained by prostaglandin E2 Major source in utero is placenta PDA Patent Ductus Arteriosus Continuous, machine-like murmur Widened pulse pressure Loss of volume in arterial tree through PDA Low diastolic pressure Increased pulse pressure Differential cyanosis Occurs when shunt reverses R —Y L Blue toes, normal fingers Patent Ductus Arteriosus Rarely remains patent (3 to 8 per 10,000 births) Associated with congenital rubella syndrome ToRCHeS infection Mother: Rash, fever, lymphadenopathy Baby: Deafness, cataracts, cardiac disease PDA common Rare in developed countries (vaccination) Consider in infants whose mothers are immigrants Alprostadil Prostaglandin El O Maintains patency of ductus arteriosus Key effect: delivers blood to lungs Useful when poor RV PA blood flow Tetralogy of Fallot Pulmonary atresia 133
Indomethacin NSAID • Inhibits cyclooxygenase Decreases prostaglandin formation Can be used to close PDA Eisenmenger's Syndrome Uncorrected ASD/VSD [PDA Right heart chronically overloaded Qp:Qs QP = Pulmonary blood flow Qs = Systemic blood flow Qp:Qs should be 1:1 • In shunts, Qp:Qs may be > 1:1 1.5:1, 2:1, 3:1, etc. Fetal Alcohol Syndrome Caused by prenatal exposure to alcohol (teratogen) RV Hypertrophy Pulmonary hypertension Shunt reverses right left Cyanosis Clubbing Polycythemia (very high Hct) PFO Patent Foramen Ovale Found in —25% adults ART' Wikipedia/Public Domain Characteristic facial features Impaired neurologic function Congenital heart defects Atrial septal defect Ventricular septal defect Tetralow of Fallot 134 Teresa Kellerman/Wikipedia Failure of foramen ovale to close after birth Can lead to stroke in patients with DVT/PE
Cyanotic Congenital Heart Disease Jason Ryan, MD, MPH Blue Babies Central cyanosis early in life Blood not going through lungs after birth Tetralogy of Fallot Transposition of great vessels Truncus arteriosus Tricuspid atresia Total anomalous pulmonary venous return Infundibulum Conus Arteriosus • "Funnel" leading to pulmonic valve Develops from bulbus cordis Smooth, muscular structure at RV outflow to PA OpenStax Colleg/Wikipedia Cyanosis Central cyanosis Cardiac output normal Blood is flowing Not enough 02 Lips Nail beds Conjunctivae Warm extremities Peripheral cyanosis Low blood flow Severe heart failure Cold extremities WaltFletcher/Wikipedia Tetralogy of Fallot Constellation of four abnormalities Ventricular septal defect (VSD) Rightward deviation of aortic valve ("overriding aorta") Subpulmonary stenosis Right ventricular hypertrophy Infundibulum Conus Arteriosus Septum displaced (moves toward RV) in TOF Causes "overriding aorta" 5-95% of aorta may lie over RV Causes VSD Usually large ("non-restrictive") 135
Infundibulum Conus Arteriosus • "Infundibular stenosis" Subpulmonary stenosis RV outflow tract obstruction Abnormal pulmonary valve Rarely main cause of obstruction Flow obstruction -Y RVH Tetralogy of Fallot Physiology Poor blood flow RV lungs Left to right shunts beneficial Bring back to pulmonary artery Diverts blood to lungs Improves oxygenation Patent ductus arteriosus Aortopulmonary collateral arteries Surgical shunt Tetralogy of Fallot X-ray Tetralogy of Fallot Physiology High resistance to flow RV -5 pulmonary artery RV outflow pulmonic stenosis Diverts blood across VSD to left ventricle Severity of flow obstruction determines symptoms Severe obstruction: severecyanosis Mild obstruction: less shunting ("pink" tets) Tetralogy of Fallot Murmur Systolic ejection murmur Crescendo-decrescendo RV outflow and pulmonic stenosis Heard best at left sternal border Single S2 S2 = closure of aortic and pulmonic valves TOF: Diseased pulmonic valve no sound VSD murmur (holosystolic) not typically heard Large VSD no murmur Tetralogy of Fallot Other Features Squatting improves symptoms Increased afterload/TPR (resists flow out of LV) Pressure rises in the aorta/left ventricle Less blood shunted RV LVvia VSD More blood to lungs Sherif Salama/ Flikr 136
Tetralogy of Fallot Other Features "Tet spells" Sudden cyanosis often when agitated Severe/complete RVOT obstruction 02, knees to chest, beta blockers (propranolol) Wikipedia/Public Domain Transposition of Great Vessels Wikipedia/ Public Domain Transposition of Great Vessels D-transposition (most common type): Aorta forms anterior and rightward of pulmonary artery Aorta arises from right ventricle Pulmonary artery from left ventricle Pulrnonay COrÜiar•y arterB fight Kshafer/WikiDoc Truncus Arteriosus Common arterial trunk Mixing of blood Failure of neural crest cells to driveformation of aorticopulmonary septum Almost always has VSD OpenStax Colleg/Wikipedia Transposition of Great Vessels Normal heart: Aorta is posterior and to right of pulmonary artery artay Coronary left Side Kshafer/WikiDoc Transposition of Great Vessels RV Aorta -5 body -5 RA RV LV-> Pulmonary artery LA -5 LV Two completely separate circuits NOT compatible with life unless shunt present Usually PDA or VSD RV No Ao Lungs 137 LA No Body PA
L-TGA L-Transposition of the Great Arteries • "Double switch": Aorta/PA and LA/ RA "Congenitally corrected TGA" Venous blood RA LV-> PA* Lungs Lungs PV LA -Y RV Aorta Two circuits notseparated Wrong connections (RV-Aorta, LV-PA) Eventually right ventricle fails Tricuspid Atresia Abnormal AVvalves from endocardial cushions No tricuspid valve No blood RA RV AS VSD TAPVR Total Anomalous Pulmonary Venous Return Normal: pulmonary veins drain to leftatrium TAPVR: pulmonary veins drain to venous system Innominate (brachiocephalic) veins -5 SVC Coronary sinus Portal vein Wikipedia/Public Domain Maternal Diabetes Infants at increased risk congenital anomalies Common congenital heart defects Transposition of great vessels Truncus arteriosus Tricuspid atresia VSD PDA Tricuspid Atresia All cases have L shunt Always seen with ASD Allows blood flow to LA All cases have R shunt Allows blood flow to lungs RVvia VSD Ao PAviaPDA TAPVR Total Anomalous Pulmonary Venous Return RV -5 Lungs Pulm Veins -5 RA RV 2. øyvind Holmstad/Wikipedia VSD RA and RV dilate Must have a right to left shunt ASD (most common) PDA Mixed (low 02) blood to body 138 Wikipedia/Public Domain
Ebstein's Anomaly Apical displacement of TV -5 small RV "Atrialization" of RV tissue Severe tricuspid regurgitation Can lead to right heart failure Wikipedia Commons Maternal Lithium Teratogen Completely equilibrates across the placenta Teratogenic effects primarily involve heart Ebstein's anomaly mostcommon Ebstein's Anomaly Right to left shunting and cyanosis if ASD High RA pressure Associated with WPW Electrical bypass tract often present Delta wave on EKG Delta Wave Pulmonary Atresia 00 Failure of pulmonic valve orifice to develop No flow from RV to lungs • In utero blood bypasses lungs (normal development) At birth: No blood flow to lungs through PV PVR should fall but does not Often co-exists vvith VSD for outflow of RV Similar to a severe form of Tetralow of Fallot Survival depends on ductus arteriosus Alprostadil given to keep DAopen 00 Pulmonary Atresia No VSD CDC/Public Domain øyvind Holmstad/Wikipedia VSD Alprostadil Prostaglandin El O Maintains patency of ductus arteriosus Key effect: delivers blood to lungs Useful when poor RV PA blood flow Tetralogy of Fallot Pulmonary atresia 139
Conotruncal Heart Defects Outflow tract anomalies Trunk = Truncus arteriosus Conus = Conus arteriosus Tetralogy of Fallot Truncus arteriosus Transposition of the great arteries 22q deletion syndromes DiGeorge syndrome (Thymic Aplasia) Immunodeficiency, hypocalcemia Conotruncal anomalies 140
Coarctation of the Aorta BC Artery Left Carotid Subclavian Coarctation of the Aorta Jason Ryan, MD, MPH Coarctation of the Aorta Coarctation of the Aorta Left BC Carotid Subclavian Artery Ductus Arteriosus Pre-ductal Coarctation BC Artery Left Carotid Subclavian Ductus Arteriosus Post-ductal Coarctation Coarctation of the Aorta Congenital disorder Usually involves thoracic aorta distal to subclavian Near insertion of ductus arteriosus • "Juxtaductal" aorta Subtypes based on location of ductus arteriosus High resistance to flow in aorta Ductus Arteriosus Shunts blood in utero Left pulmonary artery aorta Patency maintained by C02 and t prostaglandins At birth: t02 and prostaglandins • "Functional" closure 18 to 24 hours after birth Smooth muscle constriction "Anatomic" occlusion over next few days/weeks Becomes ligamentum arteriosum 141
Coarctation of the Aorta Preductal or Infantile Ductus arteriosus supplies lower extremities Poor development of collateral vessels Left BC Carotid Subclavian Artery Ductus Arteriosus Coarctation of the Aorta Preductal or Infantile Ductus closure -5 symptoms may develop All flow through aorta with severe narrowing Coarctation of the Aorta Preductal or Infantile At birth ductus arteriosus open (not closed yet) Deoxygenated blood to lower extremity Lower extremity cyanosis mayoccur BC Artery Carotid Subclavian Abrupt increase afterload Rise in LVEDP Acute heart failure LVcan dilate fail shock All caused by closure of DA BC Artery Left Carotid Subclavian Ductus Arteriosus Coarctation of the Aorta Postductal or Adult type Ductus arteriosus does not supply lower extremities Collaterals develop May go undetected until adulthood BC Left Carotid Subclavian Arteriosus Coarctation of the Aorta Preductal or Infantile Key associations: Turner syndrome (45, XO) Short stature, webbed neck 5-10% have coarctation of the aorta Johannes Nielsen/Wiki pedia Coarctation of the Aorta Lower extremities -5 low blood pressure t Renin release Salt/water retention Vasoconstriction (All) Weak pulses ("brachio-femoral delay") Upper extremities and head high blood pressure • Secondary hypertension BC Carotid Subclavian 142
Coarctation of the Aorta Key association: bicuspid aortic valve Found in up to 60% of coarctation cases Patrick J. Lynch, medical illustrator Coarctation of the Aorta Signs/Symptoms Only sign may be hypertension in arms Murmur over back between scapula Weak femoral pulses Pain with walking (claudication) Coarctation of the Aorta Signs/Symptoms 3-sign Bulge before and after coarctation "3 sign" on chestx-ray Wiki Radiography Coarctation of the Aorta Key association: intracranial aneurysms Occur in about 10% of patients with coarctation Wikipedia/Public Domain Coarctation of the Aorta Signs/Symptoms Rib notching High pressure above coarctation Intercostals enlarge to carry blood around obstruction Bulge into ribs "Rib notching" seen on chest x-ray W i ki Radi ograp hy Coarctation of the Aorta Physiology Autoregulation maintains regional blood flow Normal upper/lower perfusion despite high/low pressures Upper extremities High blood pressure --5 high flow Arterioles constrict to limit flow to normal level Local effect - not mediated by sympathetic/parasympathetic Resistance to flow is high (Q = A P / R) Lower extremities Low blood pressure Arterioles dilate to increase flow to normal level (Q Result is normal ("compensated") flow 143 = AP/ R)
Coarctation of the Aorta Complications Heart failure Pressure overload of left ventricle Aorticrupture/dissection Endocarditis/endarteritis High-low pressure across narrowing Endothelial injury Low pressure distal to narrowing Bacteria may attach more easily 144
Hypertension Jason Ryan, MD, MPH Etiology Most (90%) is primary ("essential") HTN Cause not clear Remainder (10%) secondary Sodium Intake t Posm t ADH t H20 —T ECV—• [Nal = 140meq/L Wikipedia/Public Domain Hypertension Blood pressure >140/90 Need more than one measurement Hypertension Risk Factors Family history African-American race High salt intake Alcohol Obesity Physical inactivity Hypertension Associations Stroke Heart disease Ml Heart failure Renal failure Aortic aneurysm Aortic dissection 145
Hypertension Effects Atherosclerosis - lipid/fibrous plaques in vessels Arteriosclerosis - thickening of artery wall Response to chronic hypertension Hypertension Effects Hyperplastic arteriosclerosis Arteries look like "onion skin" Occurs when hypertension is severe (usually DBP>120) "Malignant" hypertension Retinal hemorrhages, exudates, or papilledema Pacolarosa/Wikipedia Hypertension Effects Pulse pressure mayincrease Example: Normal 120/80; HTN 170/100 Stiff arteries Icompliance Distensible Vessel 120/80 Stiff Vessel 170/100 Hypertension Effects Hyalinearteriosclerosis Thickening of small arteries Seen with aging Also common with diabetes Nephron/Wikipedia Arteriolar Rarefaction Loss of arterioles Arterioles close off and get resorbed Wikipedia/ Public Domain Hypertension Effects Afterload on heart is increased Left ventricle: concentric hypertrophy Large voltage on EKG Displaced apical impulse 146
Hypertensive Urgency Severe hypertension without end-organ damage No agreed upon BP value • Usually >180/120 Hypertensive Emergency Associated with MAHA Endothelial injury -Y thrombus formation • Improved with BP control Databese Center for Life Science (DB CLS) Hypertensive Emergency Also no definite value BP usually >180/120 Patient longstanding H TN, stops meds Neurologic impairment Retinal hemorrhages, encephalopathy Renal impairment Acute renal failure Hematuria, proteinuria Cardiac ischemia Malignant Hypertension Historical term Most cases hypertension: "benign" Modestly elevated blood pressure Stable over years "Malignant hypertension" Rare form, often fatal Severe elevation ofblood pressure (diastolic >120mmHg) Rapidly progressive over 1 to 2 years Renal failure, retinal hemorrhages, ischemia 147
Secondary Hypertension Jason Ryan, MD, MPH Blood Pressure Determinants Cardiac output Increased with renal salt/water retention Total peripheral resistance Key vessels: arterioles Increased by vasoconstrictors (i.e. catecholamines) Increased by sympathetic nervous system BP = CO X TPR Obstructive Sleep Apnea Sleep-related breathing disorder Apnea during sleep Often associated with hypertension Treatment may reduce BP PruebasBMA /Wikipedia Etiology Most (90%) is primary ("essential") H TN Cause not clear Remainder (10%) secondary Chronic Kidney Disease Over 80% of patients have hypertension Multiple causes: Sodium retention Increased renin-angiotensin-aldosterone activity Increased sympathetic nervous system activity Anna Frodesiak/Wikipedia NSAlDs Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac Nonsteroidal anti-inflammatory drugs • Inhibit cyclooxygenase in kidneys Decrease synthesis ofprostaglandins PGE-2: Renal vasodilator Afferent Efferent arteriole Madher088 /Wiki pedia 148
NSAlDs Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac Na/Water excretion May cause hypertension May exacerbate heart failure Vasoconstriction JGFR capsule Efferent Pseudoephedrine Nasal decongestant Alpha-I agonist Vasoconstriction nasal blood flow HO HO OH Epinephrine OH CHs Pseudoephedrine Primary Aldosteronism Excessive levels of aldosterone secretion Not due to increased activity of RAAS system Adrenal adenoma (Conn'ssyndrome) Bilateral idiopathic adrenal hyperplasia gland Wikipedia /Public Domain Oral Contraceptive Pills OCPs Estrogen and progesterone analogs Cause mild increase in blood pressure Ceridwen/Wikipedia Cyclosporine & Tacrolimus Immunosuppressants Calcineurin inhibitors Renal vasoconstriction *salt/water retention Diltiazem: drug of choice Impairs metabolism (T drug levels) Treats HTN and allows lower dose cyclosporine to be used Primary Aldosteronism tNa reabsorption distal nephron TECV -5 tCO Hypertension TK excretion -Y hypokalemia 149
Aldosterone Escape Excess aldosterone does not lead to volume overload Usually no pitting edema, rales, increased JVP Na/Fluid retention -5 hypertension Compensatory mechanisms activated Increased ANP Increased sodium and free water excretion Result: diuresis -5 normal volume status Liddle's Syndrome Genetic disorder Increased activity of ENaC Similar clinical syndrome to hyperaldosteronism Hypertension Hypokalemia Aldosterone levels low Pheochromocytoma Catecholamine-secreting tumor Epinephrine, norepinephrine, dopamine Usually arises from adrenal gland Triad: Palpitations, headache, episodic sweating PHEochromocytoma Most patient havehypertension Diagnosis: Catecholamines breakdown products Metanephrines Vanillylmandelic acid (VMA) Primary Aldosteronism Clinical features Resistant hypertension Hypokalemia Normal volume status on physical exam Diagnosis Renin-independent aldosterone section Low plasma renin activity High aldosterone levels Drugs of choice: Spironolactone/Eplerenone Aldosterone antagonists Collecting Duct Lumen (Urine) Aldosterone Aldosterone Interstitium/Blood ATP Aldosterone H20 Intercalated Cell Cl Cushing's Syndrome Excess cortisol Often from steroid administration Other causes Cushing's Disease (pituitary oversecretes ACTH) Tumors (i.e. small cell lung cancer secretes ACTH) Adrenal tumor secretes cortisol Cortisol hypertension Increased vascular sensitivity to adrenergic agonists 150
Renal Artery Stenosis Vascular disease of renal arteries Decreased blood flow to kidneys Key exam finding: renal bruit Kidney Renal Artery Stenosis tRAAS Euvolemia TRenin Stenotic JRenin JNa Renal Artery Stenosis Increased renin, salt-water retention -5 H TN Often unilateral stenosis Normal kidney compensates Results: No signs of volume overload Renal Artery Stenosis Angiotensin Il Normal GFR depends on angiotensin Il All -5 efferent arteriole vasoconstriction Maintains GFR ACE inhibitors can precipitate renal failure Coarctation of the Aorta Fibromuscular Dysplasia Vascular disease -5 obstruction to flow Common among women Often occurs in 40s-50s Non-atherosclerotic, non-inflammatory Often involves medial layerfibroplasia Stenosis and aneurysms of vessels ("string of beads") Most common in renal and carotid arteries Can lead to renal artery stenosis BC Artery 151 Left Carotid Subclavian
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Antihypertensives Jason Ryan, MD, MPH Beta Receptors ßl receptors in heart, kidneys Increase heart rate and contractility Stimulate renin release Blockade 1 CO, 1 ECV* BP ß2 receptors Dilate blood vessels (muscle, liver) Bronchodilate Blockade does not lead to lower blood pressure Beta Blockers 131132 (nonselective) antagonists Propranolol, Timolol, Nadolol Can be used for hypertension Nadolol, Propranolol: Used in portal hypertension Beta 1 blockade: CCO, ECV BP Beta 2 blockade: L portal blood flow Timolol: Used in glaucoma Beta 1 and Beta 2 -Y aqueous humor production BP = CO X TPR 1 Circulating Heart Rate Vascular Tone Volume Contractility Beta Blockers ßl-selective antagonists Atenolol, Metoprolol, Esmolol Used for hypertension Blockade 1 CO, ECV+ BP Metoprolol: Systolic heartfailure Blocks sympathetic stimulation of heart Reduces mortality Beta Blockers ß1ß2a1 Carvedilol, Labetalol Labetalol: Hypertensive Emergency Rapid reduction in blood pressure Carvedilol: Systolic heart failure Blocks sympathetic stimulation of heart Reduces mortality 153
Beta Blockers Partial Agonists Pindolol: ß1ß2 (nonselective) Acebutolol: 131 -selective "Intrinsic sympathomimetic activity" Beta agonist when sympathetic activity is low Beta blocker when sympathetic activity is high Can cause angina through beta 1 activation Special pharmacologic properties Beta Blockers Side effects Caution in diabetes Blockade of epinephrine effects Epinephrine raises glucose levels Blockade —Y hypoglycemia 4. Victor/Flikr Blockade of hypoglycemiasymptoms glucose sweating/tachycardia Symptoms "masked" by beta blockers Beta Blockers Overdose Depression of myocardial contractility -5 shock Bradycardia/AVblock Beta Blockers Side effects Fatigue, erectile dysfunction, depression More common with older beta blockers (propranolol) Hyperlipidemia Mild increase in triglycerides Mild decrease in HDL Effect varies with different beta blockers Beta Blockers Side effects Caution in asthma/COPD ß2 receptors: bronchodilators ß2 blockade may cause a flare ßl blockers ("cardioselective") often used Decompensated heart failure ßl blockers lower cardiac output worsening of symptoms Commonly used in compensated heart failure Mortality benefit Beta Blockers Overdose Treatment: Glucagon Activates adenyl cyclase at different site from beta receptors t cAMP t intracellular Ca Increased contraction and heart rate Gl ucagon AMP 154 cAMP
al Blockers Tamsulosin, Alfuzosin, Doxazosin, Terazosin al receptors in periphery: vasoconstrict Blockade -5 vasodilation -5 U TPR IBP Used in benign prostatic hypertrophy Relax smooth muscle of bladder/prostate Increase urine flow Common side effect: Postural hypotension Tamsulosin: "U roselective" Less hypotension effect Clonidine co agonist Old, rarely used hypertension drug Key side effect: Rebound hypertension Abrupt cessation of drug (usually at high dose) Severe hypertension (SBP>200; DBP>120) Symptoms ofhigh BP and sympathetic over-activity Nervousness, sweating, headache, chest pain Also causes sedation Calcium Channel Blockers Three major classes of calcium antagonists dihydropyridines (nifedipine) phenylalkylamines (verapamil) benzothiazepines (diltiazem) Vasodilators and negative chronotropes/inotropes Alpha 2 Receptors co receptors in CNS Feedback Presynaptic receptor to nerve when NE released Activation leads to INE release Neuron NE Vascular Smooth Muscle Methyldopa co agonist Drug of choice in pregnancy Also causes sedation Norepinephrine Key side effect (rare): Hemolytic anemia RBC øyvind Holmstad/Wikipedia Calcium Channel Blockers Vascular smooth muscle effects Nifedipine>Diltiazem>Verapamil Heart rate/contractility effects Verapamil>Diltiazem>Nifedipine 155
Calcium Channel Blockers Dihydropyridines (nifedipine) •vasodilators Main effect: ITPR Non-dihydropyridines (Verapamil, diltiazem) Similar to ßl blockers Main effects: IHR; contractility Calcium Channel Blockers Dihydropyridines (nifedipine) Pre- Capillary 100 Arteriole 50 Systemic Pre-Capillary 80 Systemic Arteriole t 60 Capillary 50 Capillary 60 Calcium Channel Blockers Other Side Effects Constipation Most commonly with verapamil Elya/Wikipedia Calcium Channel Blockers Dihydropyridines (nifedipine) Used forhypertension Flushing, headache, hypotension Peripheral vasodilation Key side effect: edema Increased capillary hydrostatic pressure Pre-capillary arteriolar vasodilation James Heilman, MD/Wikipedia Calcium Channel Blockers Verapamil, diltiazem Used for hypertension Also used in heart disease Arrhythmias (atrial fibrillation) Stable angina (lower oxygen demand) Potential side effect: Negative inotropes Can precipitate heart failure Calcium Channel Blockers Other Side Effects Hyperprolactinemia Seen with verapamil Blocks calcium channels CNS dopamine release Causes hypogonadism Men: libido, impotence Pre-menopausal women: irregular menses, galactorrhea 156
Calcium Channel Blockers Other Side Effects Gingival hyperplasia Seen in all types CCB Also with phenytoin, cyclosporine Lesion /Wi kip edia Angiotensin Il Inhibition ARBs Angiotensin Il Angiotensi nogen + Renin + ACE Net Result TSalt/Water Retention TPreload TAfterload TBP All Drugs ACE Inhibitors Sympathetic System Renal Na/Cl reabsorption Arteriolar vasoconstriction Adrenal aldosterone secretion Pituitary ADH secretion + Renin Aliskiren o ACE Inhibitors Net Result TSalt/Water Retention TPreload T Afterload TBP Bradykinin Bradykinin o Sympathetic System Renal Na/Cl reabsorption Arteriolar vasoconstriction Adrenal aldosterone secretion Pituitary ADH secretion Cough Vasodilation O ACE Inhibitors A2 Inactive Metabolites Captopril, Enalapril, Lisinopril, Ramipril Angiotensin Receptor Blockers (ARBs) Candesartan, Irbesartan, Valsartan Side effects Hyperkalemia (Laldosterone) Renal failure (LGFR) ACE Inhibitors Unique Side Effects Due to increased bradykinin Dry Cough Occurs in —10% of patients Angioedema Swelling of face, tongue Can be life-threatening 157
Aliskiren Direct renin inhibitor Reduces angiotensin I levels (unique effect) Angiotensinogen + Renin Hydralazine Direct arteriolar vasodilator Rarely used forhypertension Combined with nitrates for heart failure Safe in pregnancy Causes drug-induced lupus Hypertensive Emergency Unique drugs used for therapy Intravenous, rapid acting Lowering BP too fast can cause ischemia Autoregulation of vascular beds vasoconstriction KOMUNcws/Flikr Diuretics Loop diuretics Furosemide, bumetanide, torsemide, ethacrynic acid Thiazide diuretics Hydrochlorothiazide; chlorthalidone; metolazone Potassium sparing diuretics Spironolactone, Eplerenone, Triamterene, Amiloride Drug-induced Lupus Syndrome similar to lupus Often rash, arthritis, low blood cell counts Milder than SLE Usually no associated renal failure/CNS disease Key finding: anti-histone antibodies Three drugs Hydralazine Procainamide Isoniazid Hypertensive Emergency Nitroprusside Short acting drug t intracellular cGMP t nitric oxide release Venous and arteriolar vasodilation preload (VR); afterload Cyanide toxicity with prolonged use Multiple cyanide groups per molecule Inhibits electron transport Toxic levels with prolonged infusions 158 2- Sodium Nitroprusside
Hypertensive Emergency Fenoldopam DI agonist Arteriolar vasodilation Increased urinary sodium/water excretion Maintains renal perfusion while vasodilating Orthostatic Hypotension Postural Hypotension; Orthostasis Ublood pressure due to gravity with standing Compensation from sympathetic nervous system Increased VR, CO, HR, TPR Impaired with low volume, low TPR, blunted ANS Severe IBP (>20mmHg) = orthostatichypotension Dizziness, syncope Common etiologies: Hypovolemia Hypertensive medications Reflex Tachycardia Vasodilation -Y IBP TSNS Reflex response: t HR Can be caused by vasodilators Hydralazine Alpha-I blockers Dihydropyridine calcium channel blockers Nitroglycerine May exacerbate chronic stable angina Drugs may be co-administered with ß blocker Hypertensive Emergency Labetalol ßl and al Blocker Esmolol Rapid acting intravenous [31 blocker Nicardipine, Clevidipine Intravenous dihydropyridine calcium channel blocker Orthostatic Hypotension Postural Hypotension; Orthostasis Alpha-I blockers ACE-inhibitors Especially in patients on diuretics Volume depletion TRAAS "First dose hypotension" Choosing Drugs Diabetes ACE inhibitors: Protective of kidneys Beta blockers can lower glucose and mask hypoglycemia HCTZ can increase glucose Systolic Heart Failure ACEi, beta blockers, aldosterone blockers: mortality benefit Calcium channel blockers contractility 159
Choosing Drugs Hypertension in Pregnancy Methyldopa Beta blockers, nifedipine, hydralazine Avoid: ACE inhibitors, ARBs, direct renin inhibitors Associated with congenital malformations Significant renal failure or TK Avoid: ACE-inhibitors, ARBs (IAII, laldsoterone) Avoid: Potassium sparing diuretics (t K) Avoid: Other diuretics (IECV IGFR) Calcium blockers, beta blockers usually ok 160
Heart Valves Pulmonic Tricuspid Valve Disease Jason Ryan, MD, MPH Valve Disease Stenosis Stiffening/thickening of valve leaflets Obstruction to forward blood flow Regurgitation Malcoaptation of valve leaflets Leakage of blood flow backwards across valve Valve Lesions - Diastole Occur when heart relaxes/fills Aortic regurgitation Mitral stenosis Pulmonic regurgitation Tricuspid stenosis Aortic Mitral Valve Lesions - Systole Occur when heart contracts/squeezes Aortic stenosis Mitral regurgitation Pulmonic stenosis Tricuspid regurgitation Valve Disorders Treatments Only severe valvular lesions treated Mostly surgical diseases Surgical repair Often done for mitral valve prolapse -Y mitral regurgitation Valve replacement Bioprosthetic (pig or cow) Mechanical (requires life-long anticoagulation) Valvuloplasty (stenoticlesions) 161
Stenotic Valve Disorders Stiff valve "Gradient" across valve High pressure upstream Lower pressure downstream Rheumatic Fever Jones criteria Joints: Polyarthritis (>5 joints) : Carditis (valvulitis, myocarditis, pericarditis) Nodules (subcutaneous) Erythema marginatum (rash on trunk) Sydenham chorea (jerking movement disorder) Carcinoid Heart Disease Caused by carcinoid tumors of intestines Secrete serotonin Fibrous deposits tricuspid/pulmonic valves Leads to stenosis and regurgitation Serotonin inactivated by lungs Left sided lesions rare Rheumatic Fever Occurs weeks after streptococcal pharyngitis Common in children Autoimmune: type Il hypersensitivity reaction Antibodies to bacterial M proteins cross-react Rheumatic Heart Disease Damage to heart valves by rheumaticfever Mitral valve most commonly involved Often presents years after acute rheumatic fever Many patients do not recall acute symptoms Common in developing countries Limited access to medical care for pharyngitis Often seen in immigrants to US Aortic Stenosis Pathophysiology Stiff aortic valve Systolicproblem Increased afterload 162
Aortic Stenosis Hemodynamics LVpressure systolic >> aortic pressure LVSP = 160mmHg (normal = 120) SBP = 120mmHg (normal = 120) Gradient = 40mmHg t LVEDP due to t afterload Normal Aortic Stenosis Causes Senile aortic stenosis "Wear and tear" Collagen breakdown Calcium deposition Bicuspid aortic valve Aortic Stenosis Patrick J. Lynch, medical illustrator Rarely rheumatic heart disease CDC/Public Domain Mitral Stenosis Pathophysiology Stiff mitral valve Diastolic problem LA pressure >> LVdiastolic pressure Left atrial pressure 20mmHg (normal = 10) LVEDP 5mmHg (normal = 10) Gradient = 15mmHg Decreased preload Aortic Stenosis Clinical features Systolic crescendo-decrescendo murmur Syncope: failure to tCO due to t afterload Angina: t LVEDP —Y coronary blood flow Left heart failure: t LVEDP Supravalvular Aortic Stenosis Narrowing of ascending aorta above aortic valve Seen in Williams syndrome Genetic deletion syndrome Short and Long Arms of a Chromosome p Short arm q long arm Wikipedia/Public Domain Mitral Stenosis Clinical features Caused by rheumatic fever Most common symptom: dyspnea t LA pressure pulmonary congestion Murmur: diastolic rumble with opening snap 163
Tricuspid Stenosis Very rare valve disorder Diastolic murmur at left lower sternal border Caused by rheumatic fever (with mitral disease) Tricuspid regurgitation more common Carcinoid heart disease Regurgitant Lesions Acute and chronic forms Acute regurgitation (often from endocarditis) May cause shock Activation of sympathetic nervous system Increased contractility Increased afterload Chronic regurgitation No shock Leads to chronic heart failure Sympathetic activation only if severe heart failure Aortic Regurgitation Causes Dilated aortic root leaflets pull apart Often from H TN or other aortic aneurysm Rarely from tertiary syphilis (aortitis) Bicuspid aortic valve Turner syndrome Coarctation of the aorta Endocarditis Rheumatic heart disease Almost always with mitral disease Pulmonic Stenosis Congenital defect in children Fused commissures with thickened leaflets Carcinoid heart disease Wikipedia/Public Domain Aortic Regurgitation Pathophysiology Blood leaks across aortic valve Diastolic problem Increased preload, stroke volume Increased afterload More stroke volume aorta compliance (stiffening) Blowing diastolic murmur Aortic Regurgitation Clinical features Leaking blood back into LVcauses low diastolic BP 120/80 (normal) -5 120/40 Low diastolic pressure Wide pulse pressure High cardiac output with low diastolic pressure Wide pulse pressure symptoms "Water hammer" pulses Head bobbing Many, many others (mostly historical) 164
Mitral Regurgitation Pathophysiology Blood leaks across mitral valve • Increased LA volume Starling mechanism • Increased left ventricular filling from LA Increased preload, stroke volume Reduced afterload Mitral Regurgitation Secondary causes • Ischemia damage to papillary muscle Left ventricular dilation Dilated cardiomyopathy Leaflets pulled apart "Functional" MR Hypertrophic cardiomyopathy Mitral Regurgitation Clinical Features Holosystolic murmur at apex Mitral Regurgitation Causes Primary MR caused by mitral valve prolapse Also called degenerative or myxomatous Billowing of mitral valve leaflets above annulus Common cause of mitral regurgitation Causes a systolic click Don't confuse with opening snap of mitral stenosis Mitral Regurgitation Causes Endocarditis Rheumatic heart disease Congenital Cleft mitral valve Endocardial cushion defect Down syndrome Afterload Reduction Aortic and Mitral Regurgitation In theory, afterload can improve forward flow For severe, acute regurgitation this helps For chronic disease, clinical trials with mixed results In general, these are surgical diseases Common test scenario "Best medical option?" 165
Tricuspid Regurgitation Small amount of TR normal ("physiologic TR") Holosystolic murmur at left sternal border Pathologic causes Functional TR from RV enlargement Endocarditis - classically IV drug users Carcinoid Ebstein's anomaly Pulmonic Regurgitation Most common cause: repaired Tetralogy of Fallot Repair of RVOT obstruction damages valve Endocarditis (rare) Rheumatic heart disease (rare) Tetralow of Fallot 166
Shock Jason Ryan, MD, MPH Types of Shock Cardiogenic Cardiac disorder -5 fall in cardiac output Hypovolemic Fall in intravascular volume fall in cardiac output Hemorrhage Distributive Peripheral vasodilation Septic, anaphylactic Obstructive Swan-Ganz Catheter Pulmonary artery catheter Pulmonary Capillary Wedge Pressure PCWP "Wedge Pressure" Equal to LA pressure Shock Life-threatening fall in blood pressure Poor tissue perfusion Low cardiac output Loss of contractility Low intravascular volume Peripheral vasodilation BP = CO X TPR Types of Shock Different treatments for different types ofshock Often can determine type from history Myocardial infarction cardiogenic shock Massive bleeding hypovolemic shock Shock of unclear etiology: Swan-Ganz catheter Swan-Ganz Data RA Pressure (Normal 5mmHg) RV Pressure (20/5) PA Pressure (20/10) PCWP Pressure (10) Mixed venous 02 sat Oxygen concentration after all veins mix 167
Fick Equation Oxygen Consumed = 02 Out Lungs - 02 In Lungs CO (Art 02 - Ven 02) Cardiac Output = 02 Consumption (Art 02 - Ven 02) 02 Consumption cc body size Arterial 02 Content = 02 sat on finger probe Venous 02 Content = 02 from Swan-Ganz Swan-Ganz catheter gives cardiac output Swan-Ganz Data Direct RA Pressure (Normal RVPressure (20/5) PA Pressure (20/10) PCWP Pressure (10) Mixed venous 02 sat Calculated Cardiac output 5mmHg) Systemic Vascular Resistance Cardiogenic Shock Hallmark is low cardiac output High cardiac pressures High SVR (sympathetic response) Classic cause: large myocardial infarction Also seen in advanced heart failure (depressed LVEF) Flow Equation Used to determine systemic vascularresistance AP = CO *SVR MAP - RAP CO * SVR SVR = MAP - RAP co Swan-Ganz Catheter gives SVR Hemodynamic of Shock Four major classes of shock All have different hemodynamics from Swan Swan can be used to determine etiology of shock Cardiogenic Hypovolemic Distributive Obstructive Hypovolemic Shock Poor fluid intake High fever, insensible losses Hemorrhage Low cardiac output Low cardiac pressures High SVR (sympathetic response) 168
Distributive Shock Hallmark is low SVR Diffuse vasodilation and/or endothelial dysfunction Sepsis (most common) Anaphylaxis Neurogenic Cardiac output classically high (variable) Cardiac pressures variable Major Shock Types SVR Low High Distributive Pressures Type of Shock Cardiogenic Blood Pressure HR RA Pressure RV Pressure PCWP Cardiac Output SVR Physical Exam Hypovolemic Distributive High Cardiogenic Low Hypovolemic Obstructive Shock Obstruction to blood flow from heart Low cardiac output despite normal contractility Tamponade Tension pneumothorax Massive pulmonary embolism Low cardiac output High SVR Cold skin high SVR and low CO Cardiogenic Hypovolemic Warm skin -5 low SVR and high CO Distributive Jugular venous pressure -5 high RApressure Pulmonary rales high LApressure Treatment of Shock Cardiogenic: inotropes Milrinone, Dobutamine Hypovolemic: volume Blood transfusions, IV fluids Distributive: vasopressors Phenylephrine, epinephrine, norepinephrine Obstructive: resolveobstruction Treat tamponade, embolism, tension pneumothorax 169
Swan in Valve Disease Swan in Valve Disease RV (20/5) PA (20/10) PCWP (10) LV (120/10) Ao (120/80) 15 45/15 45/30 30 120/5 120/80 RV (20/5) PA (20/10) PCWP (10) LV (120/10) Ao (120/80) 5 20/5 20/10 10 150/10 120/80 Mitral Stenosis Swan in Valve Disease RV (20/5) PA (20/10) PCWP (10) LV (120/10) Ao (120/80) 15 45/15 45/30 30 120/30 120/40 Aortic Regurgitation Giant V waves Seen in mitral regurgitation in PCPW tracing Similar to giant V waves in tricuspid regurgitation Seen in venous pressure tracing Aortic Stenosis Left Atrial Pressure 170
Pericardium Three layers Fibrous pericardium Serous pericardium Parietal layer Visceral layer Pericardial Sac Blausen Medical Communications, Inc. Pericardial Disease Jason Ryan MD, MPH Pericardial Diseases Pericarditis Tamponade Constrictive pericarditis Parietal pencardiurn (cut) Vescerat pericardium (cut) Pericardial fluid Pericardial Sac Blausen Medical Communications, Inc. Pericarditis Clinical Features Chest pain Sharp Worse with deep breath (pleuritic) Worse lying flat (supine) Better sitting up/leaning forward Fever Leukocytosis Elevated ESR Pericardial cavity between serous layers • Innervated by phrenicnerve Pericarditis referred pain to the shoulder Pericarditis Most common pericardial disorder Inflammation of the pericardium • Immune-mediated (details not known) May recur after treatment Pericarditis EKG Findings iäi 171
Pericarditis EKG Findings PR Depression Pericarditis Diffuse ST elevation PR depression Pericarditis Physical Exam Pericardial friction rub Scratchy sound Systole and diastole Pericarditis Etiology Uremic (renal failure) Pos t-myocardial infarcti on Fibrinous (days after MI) Dressler's syndrome (weeks after MI) Autoimmune disease (RA, Lupus) Pericarditis EKG Technically, 4 stages of EKG changes Stage 1: diffuse ST elevations, PRdepressions Stage 2 (—1 week later): Normal Stage 3: T wave inversions Stage 4: Normal Pericarditis Etiology Usually idiopathic Viral Classic cause is Coxsackievirus Often follows viral upper respiratory infection (URI) Bacterial Spread of pneumonia Complication of surgery Tuberculosis Fungal Pericarditis Treatment NSAIDs Steroids Colchicine Inhibits WBCs via complex mechanism Useful in gout and familial Mediterranean fever Added to NSAIDs to lower risk of recurrence 172
Myopericarditis Myocarditis = inflammation of myocardium Similar presentation to ischemia Chest pain EKG changes Increased CK-MB, Troponin Tamponade IOS Tamponade Causes Cancer metastases to pericardium Uremia Pericarditis Trauma Treatment: Drainage ofeffusion Tamponade Accumulation of pericardial fluid High pericardial pressure Filling restriction of cardiac chambers Amount of fluid variable Acute accumulation (bleeding): small amount of fluid Chronic accumulation (cancer): large amount of fluid Water Bottle Sign Tamponade Clinical features Distant heart sounds Dyspnea High left atrial pressure Pulmonary edema Elevated jugular venous pressure 173
Tamponade Clinical features Beck's Triad Distant heart sounds Elevated JVP Hypotension Seen in rapidly-developing traumaticeffusions Severe impairment LVfunction low cardiac output Slower effusions: Pericardium stretches/dilates Pulsus Paradoxus Inspiration t RV Size Septum bulges L LV Size CO Pulsus Paradoxus Measurement Technique Raise cuff pressure until no sounds heard NORMAL respirations Slowly lower cuff pressure First point (PI): intermittent sounds Second point (P2): constant sounds Pulsus = PI - P2 Pulsus Paradoxus Classic finding in tamponade Systolic BP always falls slightly oninspiration Exaggerated fall (>1 OmmHg) = pulsus paradoxus Severe fall = pulse disappears Public Domain Pulsus Paradoxus Also seen in asthma and COPD Inspiration: L left sided flow Caused by pulmonary pressure fluctuation Exaggerated in lung disease Normal lungs: 0 to -5mmHg Lung disease: Change up to 40mmHg Large drop in left sided flow pulsus paradoxus Tamponade EKG Sinus tachycardia Low voltage - EKG sees less electricity due to effusion Electrical Alternans 174
Tamponade Prominentx descent, Blunted y descent a a c Prominent x descent RA pressure during RV contracti on a in systole Equalization of Pressures Occurs when cardiac chambers cannot relax Pressure in RA, RV, LA, LVfalls but then abruptly stops Seen in tamponade and pericardial constriction Poor RV filling in diastole Parameter RA mean RV Pressure PCPW Pressure Normal 5 20/5 10 Tamponade 20 44/20 20 Constrictive Pericarditis www.learningradiology.com, courtesy of Dr. William Herring, MD, FACR. used with permission. Constrictive Pericarditis Clinical Features Dyspnea Prominent right heart failure Markedly elevated jugular venous pressure Lower extremity edema Liver congestion May lead to cirrhosis ("nutmeg liver* David Monniaux/Wikipedia Constrictive Pericarditis Fibrous, calcified scar in pericardium Loss of elasticity: stiff, thickened, sticky Can result from many pericardial disease processes Pericarditis Radiation to chest Heart surgery Constrictive Pericarditis Other Features Pulsus paradoxus uncommon (—20%) High RA, RVEDP, PCPW pressures Equalization of pressures Pericardial knock Pericardial Knock 175
Kussmaul's Sign ac v Pulsus and Kussmaul's Pulsus paradoxus: classic sign of tamponade Pulsus in tamPonade Kussmaul's sign: classic sign ofconstriction Also seen in restrictive heart disease Kussmaul's in Konstriction/Restriction • Inspiration -5 T VR -5 slight fall in mean JVP Kussmaul's sign = t JVP with inspiration Ventricle cannot accept t VR Constrictive pericarditis Restrictive cardiomyopathy RV myocardial infarction Not seen in tamponade Constrictive Pericarditis Rapid/ prominent y descent a c Ramd-y.descent Rapid filling of RV Abrupt stop in filling Myocardium adherent to pericardium In diastole: rapid relaxation and suction of RA volume Dip and Plateau Square Root Sign Right Ventricular Pressure Rapid filling, abrupt stop Dip & Plateau Normal Constrictive Pericarditis Tamponade Constriction Pulsus Kussmaul's Yes No No Yes Restrictive No Yes Venous Pressure Findings x descent y descent Tamponade Rapid Absent Constriction Rapid Constriction and Restriction Constrictive pericarditis/Restrictive heartdisease Many common features Prominent right heart failure Kussmaul's sign Rapid y descent Dip and plateau 176
Aortic Dissection Jason Ryan, MD, MPH Aortic Dissection Three layers to aorta Intima Media Adventicia Dissection tear in intima Blood "dissects" intima and media Types Type A Involves ascending aorta and/or arch Treated surgically Type B Descending aorta Can be treated medically Control hypertension/symptoms Surgical mortality high Aortic Dissection CT Angiogram es courtes Dr. ames Heilman and Wiki edia; used with ermission Com Ca rotid Adventicia Media Intima Propagation Blood enters dissection plane Spreads proximal, distal Can disrupt flow to vessels Symptoms Brachiocephalic Subclavian Diaphragm Illiacs "Tearing" chest pain radiating to back 177
Other symptoms Propagation to aorticroot Aortic regurgitation Pericardial effusion/tamponade Myocardial ischemia (obstruction RCA origin) Propagation to aortic arch Stroke (carotids) Horner's syndrome Vocal cord paralysis Other findings Blood pressure differential between arms Widened mediastinum on chest x-ray JHeuser 'Wikipedia Risk Factors General Principles Medial layer of aorta Tensile strength and elasticity Key proteins: collagen and elastin Weakness of medial layer dissection/aneurysms Common aneurysm feature: medial damage/destruction Vasa vasorum Network of small vessels primarily in adventitial layer Supplies blood to medial layer in thick vessels (i.e. aorta) Thickening (H TN) weakening of medial layer Recurrent Laryngeal Nerve Branch of vagus nerve Supplies larynx and voice box Compression: Aortic dissection Massive left atrial enlargement Diagnosis Suggested by history, exam, chest x-ray Definitive diagnosis CT scan MRI Transesophageal echocardiogram (TEE) D-dimer Sensitive but not specific Normal value makes aortic dissection unlikely Risk Factors General Principles Requires tension on wall Common in proximal aorta (near aortic valve) High tension from blood moving out of heart Worsened by hypertension Requires weakness of media layer Also caused by hypertension Seen in collagen disorders (genetic) 178
Risk Factors General Principles Cystic medial necrosis Development of cysts and necrosis in medial layer Occurs to mild degree with aging More rapid with: Bicuspid aortic valve Marfan syndrome Common in ascending thoracic aneurysms Aortic Aneurysms Dilation/bulge of aorta More than 1.5x normal • Involves all three 3 layers Thoracic (TAAs) Abdominal (AAAs) Thoracic Aortic Aneurysms Symptoms Most are asymptomatic Can cause aortic regurgitation Surgery if size >5.0cm Risk Factors Aortic Dissection Aortic damage H TN - #1 risk factor Atherosclerosis Thoracic aneurysm Abnormal collagen Marfan Syndrome Ehlers-Danlos Others Bicuspid aorticvalve Turner Syndrome (bicuspid, coarctation) Tertiary syphilis: Aortitis Thoracic Aortic Aneurysms Important risk factor for dissection Usually occur in proximal/ascending aorta Usually seen in association with another disorder Marfan, Turner, Bicuspid aortic valve, Syphilis Family history of aneurysm important May be associated with atherosclerosis More common in descending aorta Occur in association with atherosclerosis risk factors H TN, smoking, high cholesterol Abdominal Aortic Aneurysms More common than thoracic aneurysms Classically taught as a disease ofatherosclerosis Infrarenal aorta most affected by atherosclerosis Also most common site of AAA Current research suggests manyfactors Genetic, environmental, hemodynamic, immunologic 179
Abdominal Aortic Aneurysms Risk Factors Smoking: strongest association with AAA Males: 1 Ox more common men vs. women Age Rare before 55 As high as 5% in men >65 HTN, hyperlipidemia Aortic Rupture Usually from trauma Most common site is isthmus Isthmus Abdominal Aortic Aneurysms Most are asymptomatic Some detected on physical exam Pulsatile mass from xiphoid to umbilicus Natural history is enlargement rupture Followed with ultrasound or CT scan Surgery if >5. Ocm 180
Cardiac Tumors Jason Ryan, MD, MPH Myxoma Myxoma Mesenchymal cells (undifferentiated cells) Endothelial cells Thrombus/clot Mucopolysaccharides Cardiac Tumors Myxoma Most common 10 cardiac tumor Rhabdomyomas Most common 10 cardiac tumor children Metastatic tumors Most common cardiac tumor overall Myxoma Common in the left atrium (80%) Usually attached to atrial septum Often at the border offossa ovalis Benign (do not metastasize) Myxoma Often cause systemicsymptoms "B symptoms" Fevers, chills, sweats Can embolize -5 stroke Construction Deal Mkting 181
Myxoma May disrupt mitral valve function Regurgitation Heart failure Can sit in mitral valve "Ball in valve" Mitral stenosis symptoms Syncope or sudden death Auscultation: Diastolic "tumor plop" Cardiac Rhabdomyomas Associated with tuberous sclerosis (90%) Autosomal dominant genetic syndrome Mutation in TSCI or TSC2 gene TSCI: Hamartin TSC2: Tuberin Mutations -5 widespread tumor formation Cardiac Rhabdomyomas Tumors of muscle cells Benign (do not metastasize) Usually children (most
Tuberous Sclerosis Herbert L Fred, MD and Hendrik A. van Dijk Tuberous Sclerosis Mohd Hanafi 183
Hypertrophic Cardiomyopathy Jason Ryan, MD, MPH Hypertrophic Cardiomyopathy Names Hypertrophic cardiomyopathy (HCM) Hypertrophic obstructive cardiomyopathy (HOCM) • Idiopathic hypertrophic subaortic stenosis (IHSS) Morphologic Variants Zorkun/Wikipedia Hypertrophic Cardiomyopathy HCM Genetic disorder caused by gene mutations About 50% cases familial (50% sporadic) Autosomal dominant Variable expression Significant variation in severity of symptoms Many variations in location/severity of hypertrophy Wikipedia/Public Domain HCM Often single-point missense mutations Point mutation altered amino acid in protein 15+ genes with 1500+ mutations identified Often involve genes for cardiac sarcomere proteins Beta-myosin heavy chain (40% cases) Myosin binding protein (40% cases) 184
HCM Histology Myocyte disarray (excessive branching) Hypertrophy • Interstitial fibrosis Zorkun/Wikipedia Myokard/Wikipeedia HCM Clinical Features Sudden cardiac death Abnormal myocytes -Y ventricular arrhythmias Most common cause SCD in young patients Syncope Arrhythmias may lead to syncope Thickened myocardium LVOT obstruction Mitral regurgitation HCM Clinical Features Problem #2 : Outflow obstruction problem Thickened myocardium obstructs blood leaving LV Same physics and symptoms as aortic stenosis Heart failure, chest pain, exercise-induced syncope Treated with surgery Beta blockers (l contractility) Ca blockers (verapamil) HCM Clinical Features Many patients asymptomatic Heart failure Diastolic dysfunction Impaired emptying due to LVOT obstruction Chest pain (angina) Increased 02 demand HCM Clinical Features Problem #1: Arrhythmia problem Thick myocardium vulnerable to arrhythmias Most serious is ventricular tachycardia -Y sudden death Exercise (catecholamines) increase risk SCD Sudden death in athletes Defibrillators for high risk patients Avoidance of exercise HCM Clinical Features #3: Mitral valve problem High velocity in LVOTtugs mitral valve chords and leaflets Causes systolic anterior motion (SAM) of mitral valve Over time this leads to mitral regurgitation 00 185
HCM Clinical Features Systolic ejection murmur Caused by outflow tract obstruction Sounds just like AS unless you do maneuvers Lots of associated abnormal heart sounds Holosystolic murmur of MR Paradoxical split S2 HCM Maneuvers Valsalva Patient bears down as ifhaving a bowel movement Or blows out against closed glottis Increase thoracic pressure compression of veins* LVR Less VR -5 Less preload —Y Smaller LV cavity Obstructing septum moves further into the outflow tract Murmur INCREASES in intensity HCM Other maneuvers Raising the legs Increases venous return More VR -5 More preload -Y Bigger LV cavity This moves the obstructing septum out of the way Murmur DECREASES in intensity Standing Opposite mechanism of leg raise Murmur INCREASES in intensity HCM Maneuvers For any HCM maneuver, think about size of LV t LVsize -Y murmur U LVsize -5 t murmur HCM Maneuvers Squatting Forces blood volume stored in legs to return to heart Preload rises -5 size of LVincreases less obstruction Murmur DECREASES in intensity Wikipedia Aortic Stenosis Both HCM and AS cause a systolic ejection murmur Less effect of maneuvers on aortic stenosis Fixed obstruction Opposite effects of maneuvers in aorticstenosis Less preload -5 less flow -5 quieter AS murmur 186
HCM Maneuver Summary Valsalva INCREASE Standing -5 INCREASE • Squatting DECREASE Leg Raise DECREASE HCM Associations Friedreich Ataxia Autosomal recessive CNS disease Trinucleotide repeat disorder Spinocerebellar symptoms Often have concentric left ventricular hypertrophy Also septal hypertrophy Wikipedia/Public Domain Cardiac Hypertrophy Rare Pathologic Causes Fabry Disease Lysosomal storage disease Deficiency of a-galactosidase A Neuropathy, skin lesions, lack ofsweat Left ventricular hypertrophy HCM Associations Maternal diabetes Infants: transient hypertrophic cardiomyopathy Usually thickening of interventricular septum May have small LVchamber -5 obstruction in newborn Resolves by a few months of age øyvind Holmstad/Wikipedia Cardiac Hypertrophy Other Causes Hypertension Valve disease Athlete's heart Pixabay Cardiac Hypertrophy Rare Pathologic Causes Pompe Disease Glycogen storage disease (develops in infancy) Acid alpha-glucosidase deficiency Enlarged muscles, hypotonia Cardiac enlargement 187
Endocarditis Jason Ryan, MD, MPH Endocarditis Echocardiogram Regurgitant Valve Disease Aortic regurgitation Mitral regurgitation Tricuspid regurgitation Endocarditis Inflammation of endocardium of heart Usually involves cardiac valves Often causes new regurgitation murmur Consequence ofbacteremia General Symptoms Fever Chills Sweats Petechiae Small vessel inflammation Leakage of blood James Heilman, MD Embolic Symptoms Brain (stroke) Spinal cord (paralysis) Eye (blindness) Legs (ischemia) Splenic or renal infarction Pulmonary embolism (tricuspid) Coronary artery (acute myocardial infarction) 188
Endocarditis Stigmata Physical exam findings in endocarditis Caused by septic emboli and immune complexes Very rare in modern era Diagnosis Major Duke Criteria Positive blood cultures Vegetation on echocardiogram Minor Criteria Fever Risk factors Roth spots, Osler nodes, Janeway lesions, 2 major, 1 major 3 minor, or 5 minor Staph Aureus Gram positive cocci Catalase positive Coagulase positive splinters Endocarditis Stigmata Roth spots Retinal lesions Red with pale center Osler nodes Painful bumps on pads of fingers and toes Janewaylesions Nontender red macules on palms and soles Splinter hemorrhages Reddish-brown lines under fingernails Microbiology Staphylococcus aureus Viridans streptococcus Streptococcus Bovis Enterococcus Staphylococcus epidermidis Culture negative endocarditis Libman-Sacks Staph Aureus Causes acute endocarditis Rapid, severe infection Symptoms occur over days Joydeep/wikipedia May infect tricuspid valve in IV drug users Iqbal Osman/Flikr Can occur in patients with normal heart valves No pre-disposing valvular heart condition 189
Viridans Streptococcus Group of gram positive cocci S. mitis, S. mutans, S. sanguinis Catalase negative Mouth flora Endocarditis may occur after dental procedure Wikipedia/Public Domain Viridans Streptococcus Causes subacute endocarditis Less severe symptoms Symptoms occur over days to weeks Enterococcus Endocarditis Gram positive cocci Lancefield group D Normal gut bacteria Usually a subacute endocarditis course Commonly occurs in older men Associated with manipulation of GI/GU tract Abdominal surgery Urinary catheter TURP for treatment of BPH Viridans Streptococcus Low virulence bacteria Often affect damaged valves Bacteria synthesize dextran Dextran adheres to fibrin Fibrin found with endothelial damage Classic predisposing condition: mitral valve prolapse Streptococcus Bovis Gram positive cocci Lancefield group D Normal gut bacteria Associated with colon cancer All subtypes associated with cancer Strongest association: S. gallolyticus (S. bovis type 1) Prosthetic Valve Endocarditis Occurs with mechanical or biologic valves Rarely cured with antibiotics Usually requires repeat valve surgery Similar bacteria to native valve endocarditis Staphylococcus epidermidis Rarely cause endocarditis except in prosthetic valves Stif Komar/Wikipedia 190
Staphylococcus Epidermidis Catalase positive Coagulase negative (unlike S. Aureus) Most common coagulase negative staphylococcus Normal skin flora Low virulence Commonly cause infection of prosthetic material Cardiac valves Intravascular catheters Prosthetic joints Coxiella Burnetii Zoonotic bacteria (transferred from animals) Obligate intracellular bacteria Found in farm animals Cattle, sheep and goats Abortions in farm animals: Coxiella placenta infection Humans inhale aerosolized bacteria from animals Causes Q fever Bartonella Bartonella quintana Small, gram-negative rod Transmitted by lice Patients with poor hygiene Bartonella henselae Found in cats Causes cat scratch fever Bruce Blaus/Wiki pedia Inge Wallumrød/Pexels.com Culture Negative Endocarditis Evidence of endocarditis with sterile blood cultures Caused by rare bacteria difficult to culture Coxiella burnetii Bartonella Y tambe/Wikipedia Coxiella Burnetii Acute Q fever Flu-like illness May present as pneumonia More than half of cases: no symptoms Chronic Q fever Most common manifestation is endocarditis NBTE Non-bacterial, thrombotic endocarditis Libman-Sacks Endocarditis or Marantic endocarditis Lesions on valves that look like endocarditis Found on both sides of valve Mitral valve most common Formed by thrombus, immune complexes Seen in hypercoagulablestates Advanced malignancy Systemic lupus erythematosus 191
NBTE Non-bacterial, thrombotic endocarditis Often asymptomatic identified at autopsy Rarely cause regurgitation or murmurs Thrombus easily dislodges embolization Most patients asymptomatic until embolism occurs May embolize to spleen, kidney, skin, extremities May cause stroke Can cause myocardial infarction Bacterial Endocarditis Complications May form abscess beneath valve annulus Persistent fever, bacteremia often indicates abscess Aortic valve abscess can lead to heart block AVnode dysfunction Prophylaxis Conditions Prosthetic valves Prior endocarditis Cyanotic congenital heart disease Heart transplants Amoxicillin Clindamycin Procedures Dental work Respiratory procedures Skin surgery Bacterial Endocarditis Treatment Several weeks appropriate antibiotics Broad spectrum antibiotics initially Drug therapy changes when bacteria identified Valve surgery sometimes required Large vegetation Severe valve disease heartfailure Prophylaxis Primary prevention for bacterial endocarditis Done before high-risk medical procedures Antibiotics given to some high-risk patients New guidelines restrict to highest risk circumstances 4 Scotth23/ Pixabay 192

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