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Aortic Regurgitation

Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) (AR) is a cardiac condition characterized by the backflow of blood from the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy to the left ventricle during diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle. Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) is associated with an abnormal aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy and/or aortic root stemming from multiple causes, commonly rheumatic heart disease Rheumatic Heart Disease Cardiac manifestation of systemic rheumatological conditions, such as rheumatic fever. Rheumatic heart disease can involve any part the heart, most often the heart valves and the endocardium. Rheumatic Fever as well as congenital Congenital Chorioretinitis and degenerative valvular disorders. Acute valvular insufficiency, which rapidly progresses to cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock, is an emergency requiring immediate aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy surgery. Chronic AR develops gradually, allowing the left ventricle to adapt to the increased stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle. Thus, echocardiogram Echocardiogram Transposition of the Great Vessels shows left ventricular hypertrophy Ventricular Hypertrophy Tetralogy of Fallot and dilation along with valvular abnormalities. Eventually, heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) occurs as the left ventricle is unable to handle the hemodynamic overload. Aortic valve replacement Aortic valve replacement Aortic Stenosis is the mainstay of treatment for AR with left ventricular dysfunction.

Last updated: Jan 16, 2024

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) (AR) or aortic insufficiency:

  • The backflow of blood to the left ventricle (LV) through the aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy during diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle 
  • Caused by the incomplete closure of the valve leaflets (which normally facilitate unidirectional flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure of blood from the left ventricle)
  • Abnormalities involve aortic root and/or aortic valves.
  • Onset can be acute or chronic.

Epidemiology

  • Rheumatic heart disease Rheumatic Heart Disease Cardiac manifestation of systemic rheumatological conditions, such as rheumatic fever. Rheumatic heart disease can involve any part the heart, most often the heart valves and the endocardium. Rheumatic Fever: most common cause of AR worldwide
  • Men > women
  • In developed countries, the most common causes are:
    • Aortic root dilation
    • Congenital Congenital Chorioretinitis bicuspid aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy 
    • Calcific aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy disease
  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency increases in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship > 50 years of age.

Etiology

  • Acute aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • 2 most common causes (native valve):
      • Infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
      • Type A aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection
    • Others:
      • Chest trauma
      • Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
      • Deterioration of prosthetic aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy
      • Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome (aortic balloon valvotomy Balloon valvotomy Percutaneous procedure to separate and stretch the valve leaflets to increase the valve opening. Tricuspid Stenosis or transcatheter aortic valve implantation Transcatheter aortic valve implantation Surgical treatment for severe aortic valve stenosis. Transcatheter aortic valve replacement (TAVR) is used as an alternative option in patients who are deemed at high risk or inoperable for traditional open-heart surgery. Aortic Stenosis)
  • Chronic aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • Bicuspid valve (most common congenital Congenital Chorioretinitis cause of AR)
    • Rheumatic heart disease Rheumatic Heart Disease Cardiac manifestation of systemic rheumatological conditions, such as rheumatic fever. Rheumatic heart disease can involve any part the heart, most often the heart valves and the endocardium. Rheumatic Fever 
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disorder: Marfan’s syndrome, Ehlers-Danlos syndrome Ehlers-Danlos syndrome Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders that are characterized by hyperextensible skin, hypermobile joints, and fragility of the skin and connective tissue. Ehlers-Danlos Syndrome
    • Tertiary syphilis Tertiary Syphilis Syphilis (due to expanding aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms)
    • Vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus: giant cell arteritis Giant Cell Arteritis Giant cell arteritis (GCA), also known as temporal arteritis, is a type of large-vessel vasculitis that predominantly affects the aorta and its major branches, with a predilection for the branches of the carotid (including the temporal artery). Giant cell arteritis is defined by inflammatory leukocytes in the vessel walls leading to reactive damage, ischemia, and necrosis. Giant Cell Arteritis, Takayasu’s arteritis
    • Ankylosing spondylitis Ankylosing spondylitis Ankylosing spondylitis (also known as Bechterew’s disease or Marie-Strümpell disease) is a seronegative spondyloarthropathy characterized by chronic and indolent inflammation of the axial skeleton. Severe disease can lead to fusion and rigidity of the spine. Ankylosing Spondylitis ( aortitis Aortitis Inflammation of the wall of the aorta. Ankylosing Spondylitis)
    • Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
    • Medications: fenfluramine and dexfenfluramine (induce valvular degeneration)

Pathophysiology

Acute AR

  • Abrupt dysfunction of aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy → failure of valve to coaptate
  • Sudden increase in backflow of blood into the LV → increase in LV diastolic pressure
  • LV unprepared for the increased volume → decreased cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics  → tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children to compensate
  • Rapid rise in LV diastolic pressure closes the mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy prematurely → ↑ pulmonary venous pressure → pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema and cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock

Chronic AR

  • Aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy unable to close → portion of stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle leaks back to the LV
  • Regurgitant flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure → increases end-diastolic volume End-diastolic volume Cardiac Cycle and wall stress 
  • LV adapts to volume overload by eccentric hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation and dilation → allows larger stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle 
  • Over time, increased stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle → distends peripheral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology and ↑ systolic pressure
  • In advanced disease, LV reaches maximum diameter and cannot keep up with the hemodynamic load → LVEF gradually declines → left heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) symptoms 
  • Elevated LV mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast → increases myocardial oxygen requirements → myocardial ischemia Myocardial ischemia A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary artery disease), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Coronary Heart Disease and exertional chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
Aortic regurgitation

Pathophysiology of acute and chronic aortic regurgitation

Image by Lecturio.

Clinical Presentation

Acute AR

  • Medical emergency!
  • Signs and symptoms from pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema and cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Exam shows:
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, diaphoresis
    • Soft S1 S1 Heart Sounds due to early mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy closure 
    • Soft systolic murmur (from increased blood volume) + early low-pitched diastolic AR murmur → “to-and-fro” murmur at the cardiac base

Chronic AR

Symptoms:

  • Initially asymptomatic (when LV is able to compensate)
  • Symptoms start with reduced LV function.
    • Palpitations Palpitations Ebstein’s Anomaly ( tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children)
    • Exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
    • Orthopnea Orthopnea Pulmonary Edema, paroxysmal nocturnal dyspnea Paroxysmal nocturnal dyspnea A disorder characterized by sudden attacks of respiratory distress in at rest patients with heart failure and pulmonary edema. It usually occurs at night after several hours of sleep in a reclining position. Patients awaken with a feeling of suffocation, coughing, a cold sweat, and tachycardia. When there is significant wheezing, it is called cardiac asthma. Pulmonary Edema
    • Chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways (nighttime angina due to ↓ sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology = ↓ diastolic pressure)

Signs:

  • Inspection Inspection Dermatologic Examination: hyperdynamic apical impulse displaced laterally and inferiorly
  • Auscultation:
  • Widened pulse pressure (systolic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, ↓ diastolic pressure)
    • Hill’s sign:
      • Strong specificity
      • Popliteal cuff systolic pressure exceeds brachial cuff pressure by > 20 mm Hg on recumbent position
    • Corrigan pulse:
      • “Water hammer” or “ collapsing pulse Collapsing Pulse Cardiovascular Examination” in radial/brachial/ carotid arteries Carotid Arteries Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. Carotid Arterial System: Anatomy
      • Abrupt distention of peripheral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology (rapid rise of arterial pulse) with quick collapse
    • Bisferiens pulse: biphasic pulse from the backflow of blood (early diastole Diastole Post-systolic relaxation of the heart, especially the heart ventricles. Cardiac Cycle)
    • Becker’s sign: visible systolic pulsation in retinal arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology
    • Landolfi’s sign: constriction and dilation of pupils with heartbeat
    • Traube’s sign:
      • “Pistol shot” pulse
      • Booming systolic and diastolic sounds in femoral arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
    • Muller’s sign: systolic pulsations of the uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess
    • Duroziez’s sign:
    • Mayne’s sign: drop of at least 15 mm Hg in diastolic blood pressure when arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy is raised
    • Quincke’s pulse: visible pulsations in fingernail bed on compression Compression Blunt Chest Trauma of fingernail
    • de Musset’s sign: head bobbing with heartbeat
    • Rosenbach’s sign: systolic pulsations of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy
    • Gerhard’s sign: systolic pulsations of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy
Cardiac murmurs after correction

Phonocardiograms of abnormal heart sounds caused by the following cardiac defects:
aortic regurgitation, mitral valve prolapse, mitral stenosis (MS), aortic stenosis (AS), tricuspid regurgitation, hypertrophic obstructive cardiomyopathy (HOCM), atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA)

Image by Lecturio.

Audio:

This audio clip is an example of aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD). It is characterized by a blowing, decrescendo murmur occurring right after S2 S2 Heart Sounds.

Heart sound by The Regents of the University of Michigan. License: CC BY-SA 3.0

Diagnosis

Transthoracic echocardiography Transthoracic Echocardiography Imaging of the Heart and Great Vessels ( TTE TTE Imaging of the Heart and Great Vessels)

  • Confirms diagnosis and severity of AR; also used for serial monitoring
  • Evaluates aortic root and aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy anatomy 
  • Evaluates LV:
  • Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography): evaluates central jet width and regurgitant volume/ flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure/orifice area
  • Findings in both acute and chronic AR: 
    • Abnormal or normal but stretched valve
    • Severe AR: ↑ central jet width/↑ regurgitant volume/↑ regurgitant orifice area/holodiastolic flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure reversal in descending aorta Descending aorta Mediastinum and Great Vessels: Anatomy
    • Mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy: anterior mitral leaflet shows diastolic fluttering 
  • Findings in acute AR:
    • Done bedside
    • LV size usually normal
  • Findings in chronic AR: 

Transesophageal echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) ( TEE TEE Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues using a transducer placed in the esophagus. Imaging of the Heart and Great Vessels)

  • Performed if TTE TTE Imaging of the Heart and Great Vessels is suboptimal
  • Other indications:
    • Infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
    • Aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection (helps determine surgical options)

Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) ( ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG))

Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests

  • Acute AR:
    • Prominent aortic root
    • Enlarged cardiac silhouette (in aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection + pericardial effusion Pericardial effusion Fluid accumulation within the pericardium. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of thoracic duct. Severe cases can lead to cardiac tamponade. Pericardial Effusion and Cardiac Tamponade)
    • Pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
  • Chronic AR: 
    • Aortic dilation/calcification
    • Cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly

Cardiac Magnetic Resonance ( CMR CMR Imaging of the Heart and Great Vessels)

  • Used if TEE TEE Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues using a transducer placed in the esophagus. Imaging of the Heart and Great Vessels is suboptimal in chronic AR
  • Evaluates AR severity
  • Most accurate non-invasive technique for LV end-systolic and diastolic volumes
  • Not for widespread use due to expense and limited availability 
  • Incompatible with metallic hardware
Qualitative grading of aortic regurgitation

Echocardiography of a 19-year-old patient. Parasternal long axis view of aortic valve in diastole (a) shows moderate regurgitation (*). Corresponding four-dimensional flow cardiovascular magnetic resonance (4D flow CMR)  images showing the moderate aortic regurgitation (b and c). *: regurgitant jet.

Image: “Qualitative grading of aortic regurgitation” by Chelu RG, et al. License: CC BY 4.0

Cardiac Catheterization Cardiac Catheterization Procedures in which placement of cardiac catheters is performed for therapeutic or diagnostic procedures. Cardiac Surgery

  • Utilized to assess coronary anatomy prior to surgery (for chronic AR)
  • Provides additional information if with conflicting clinical findings:
    • LV size and EF EF Cardiac Cycle 
    • Number of leaflets 
    • Severity of AR
    • Aortic root size

Treatment and Prognosis

Acute AR

  • Emergency aortic valve replacement Aortic valve replacement Aortic Stenosis or repair
  • While awaiting surgery, interim use of:
    • IV vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease) such as nitroprusside Nitroprusside A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins. Nitrates ( afterload Afterload Afterload is the resistance in the aorta that prevents blood from leaving the heart. Afterload represents the pressure the LV needs to overcome to eject blood into the aorta. Cardiac Mechanics reduction) 
    • Inotropic agents such as dobutamine Dobutamine A catecholamine derivative with specificity for beta-1 adrenergic receptors. Sympathomimetic Drugs (↑ cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics)
  • Temporary delay in surgery so antibiotics can be given in infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
    • If patient is stable
    • Immediate surgery in hemodynamic instability or abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease formation
  • Avoid intra-aortic balloon pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols (worsens AR)
  • Avoid beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) (↓ compensatory tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, ↓ cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics)

Chronic AR

  • Monitor disease course ( TTE TTE Imaging of the Heart and Great Vessels):
    • Frequency of examination depends on symptoms, AR severity, LV size and function
    • In case of bicuspid aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy: Also monitor aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms if present.
  • Physical activity:
    • The following are recommended for athletes with AR:
      • Yearly history and physical exam with Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography) echocardiogram Echocardiogram Transposition of the Great Vessels 
      • Exercise testing (to level of competition): to confirm asymptomatic status and blood pressure response to activity
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis prophylaxis Prophylaxis Cephalosporins (for procedure):
    • Not recommended in native valve disease
    • Indicated in prosthetic heart valve or prior infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
  • Medical management:
    • For symptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe AR (surgical and non-surgical candidates), medications include:
      • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
      • Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers ( ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication
      • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
      • Mineralocorticoid receptor antagonists Mineralocorticoid receptor antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Potassium-sparing Diuretics 
      • Digoxin Digoxin A cardiotonic glycoside obtained mainly from digitalis lanata; it consists of three sugars and the aglycone digoxigenin. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. Cardiac Glycosides
    • For asymptomatic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with severe AR + LV dysfunction (non-surgical candidates): ACE inhibitors ACE inhibitors Truncus Arteriosus or ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication
    • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension control: ACE inhibitors ACE inhibitors Truncus Arteriosus, ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication, or calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers
  • Surgical management ( aortic valve replacement Aortic valve replacement Aortic Stenosis or AVR AVR Aortic Stenosis):
    • Symptomatic severe AR
    • Asymptomatic:
      • Severe AR LVEF < 50%
      • Severe AR with normal LVEF ( ≥ 50%) but with an end-systolic dimension of > 50 mm
      • Severe AR with normal LVEF ( ≥ 50%) but with progressive severe LV dilation (LV end-diastolic dimension > 65 mm); with low surgical risk
      • Severe AR who are undergoing cardiac surgery Cardiac surgery Cardiac surgery is the surgical management of cardiac abnormalities and of the great vessels of the thorax. In general terms, surgical intervention of the heart is performed to directly restore adequate pump function, correct inherent structural issues, and reestablish proper blood supply via the coronary circulation. Cardiac Surgery for other indications
      • Moderate AR who are undergoing other cardiac surgery Cardiac surgery Cardiac surgery is the surgical management of cardiac abnormalities and of the great vessels of the thorax. In general terms, surgical intervention of the heart is performed to directly restore adequate pump function, correct inherent structural issues, and reestablish proper blood supply via the coronary circulation. Cardiac Surgery

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with acute AR: high operative risk
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with asymptomatic chronic AR:
    • Favorable prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas 
    • When monitored, LV dysfunction is detected early, even before symptoms
  • Symptomatic chronic AR: 

Differential Diagnosis

Differential diagnoses of AR include the following conditions:

  • Aortic stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) (AS): one of the most common valvular heart diseases; characterized by narrowing of the aortic outlet. This narrowing leads to restriction of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure from the LV to the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy. Aortic stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) is heard as a systolic crescendo-decrescendo murmur in the 2nd intercostal space. Diagnosis is by echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA). Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic AS develop exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, angina, and syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope.
  • Mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD): a mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy pathology that leads to leakage of blood from the LV to the left atrium during systole Systole Period of contraction of the heart, especially of the heart ventricles. Cardiac Cycle. Examination shows a holosystolic murmur Holosystolic Murmur Tricuspid Valve Atresia (TVA) at the apex (left 5th intercostal space at the midclavicular line). Diagnosis is confirmed by  echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA). Presenting symptoms are frequently exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia.
  • Aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection: a tear in the intima of the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy that can expand back into the heart, causing dilation and insufficiency of the aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy. Aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection in the ascending aorta Ascending aorta Mediastinum and Great Vessels: Anatomy or aortic root is manifested as severe tearing chest pain Tearing Chest Pain Chest Pain. Computed tomography angiogram establishes the diagnosis.
  • Aortic aneurysm Aortic aneurysm An abnormal balloon- or sac-like dilatation in the wall of aorta. Thoracic Aortic Aneurysms: an abnormal dilation of the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy, usually caused by degenerative aortic disease; can lead to progressive dilation of the aortic root. Aortic aneurysm Aortic aneurysm An abnormal balloon- or sac-like dilatation in the wall of aorta. Thoracic Aortic Aneurysms is often asymptomatic, found incidentally on CT or echocardiogram Echocardiogram Transposition of the Great Vessels. Symptoms are noted when the aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms compresses surrounding structures. Ruptured aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms is a life-threatening emergency.
  • Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction: an acute blockage of the coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology supplying the heart, which can predispose structural valvular incompetence. The condition commonly presents with chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and is diagnosed with ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) and cardiac enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes.
  • Infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis: an infection of the lining of the heart,  most frequently affecting the cardiac valves. The condition is frequently caused by Staphylococci, Streptococci, and Enterococci. Examination shows fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever with a new heart murmur. Diagnosis is by history, blood cultures, and echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA).
  • Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation: a form of supraventricular arrhythmia. Diagnosis is by ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG), which shows “irregularly irregular” heartbeat with no distinct P waves and narrow QRS complexes. Chronic mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) may lead to dilation of the left atrium, which can lead to the development of atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation.
  • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) with reduced ejection fraction Ejection fraction Cardiac Cycle: a chronic, progressive condition characterized by left ventricular dysfunction from impaired myocyte contractility, which leads to subsequent volume overload. Risk factors include hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, coronary artery Coronary Artery Truncus Arteriosus disease, and diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus. Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) can develop with or without valvular abnormalities.

References

  1. Dewaswala, N.; Chait, R. (2020). Aortic Regurgitation. https://www.ncbi.nlm.nih.gov/books/NBK555944/
  2. Gaasch, W.; Otto, C.; Yeon, S. (2018). Natural history and management of chronic aortic regurgitation in adults. UpToDate. Retrieved Sept 10, 2020, from https://www.uptodate.com/contents/natural-history-and-management-of-chronic-aortic-regurgitation-in-adults
  3. Gaasch, W.; Otto, C.; Yeon, S. (2019). Clinical manifestations and diagnosis of chronic aortic regurgitation in adults. UpToDate. Retrieved 10 Sept 2020, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-chronic-aortic-regurgitation-in-adults
  4. Otto, C.; Gaasch, W.; Yeon, S. (2020). Acute aortic regurgitation in adults. UpToDate. Retrieved 10 Sept 2020, from https://www.uptodate.com/contents/acute-aortic-regurgitation-in-adults
  5. Wang, S.; O’Brien, T. (2018, Nov). Aortic Regurgitation. Medscape. https://emedicine.medscape.com/article/150490-overview

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