Endocarditis (Clinical)

Overview

Definition

• 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 ( IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis) is caused by infection or inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the inner lining of the heart ( endocardium Endocardium The innermost layer of the heart, comprised of endothelial cells. Heart: Anatomy), most commonly affecting the heart valves.
• Noninfective endocarditis Noninfective endocarditis Formation of a non-infectious thrombus, referred to as vegetation, on previously undamaged endocardium. It usually occurs as a complication of connective-tissue diseases and cancers because of the associated hypercoagulable state. Endocarditis (NIE), or nonbacterial thrombotic endocarditis Nonbacterial Thrombotic Endocarditis Paraneoplastic Syndromes (NBTE)/aseptic 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, results from the formation of sterile Sterile Basic Procedures platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology and fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis thrombi on cardiac valves and endocardium Endocardium The innermost layer of the heart, comprised of endothelial cells. Heart: Anatomy.

Epidemiology^[5,8–10]

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:

• Most common form of 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
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 11–15 cases per 100,000 persons per year
• Mean age: 60.8 years (> 50% are > 50 years of age)
• 3 times more common in men

Noninfective endocarditis Noninfective endocarditis Formation of a non-infectious thrombus, referred to as vegetation, on previously undamaged endocardium. It usually occurs as a complication of connective-tissue diseases and cancers because of the associated hypercoagulable state. Endocarditis:

• Rare
• Often found on autopsy
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 0.9%–1.6%
• Common age group: 30–70 years
• No sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria predilection

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 etiologies^[5,8–10]

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 may be caused by numerous organisms; the list below is not exhaustive.

• Staphylococci:
  • Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess (most common)
  • S. epidermidis S. epidermidis A species of staphylococcus that is a spherical, non-motile, gram-positive, chemoorganotrophic, facultative anaerobe. Mainly found on the skin and mucous membrane of warm-blooded animals, it can be primary pathogen or secondary invader. Staphylococcus
• Streptococci:
  • Streptococcus viridans Streptococcus viridans A large heterogeneous group of mostly alpha-hemolytic streptococci. They colonize the respiratory tract at birth and generally have a low degree of pathogenicity. This group of species includes Streptococcus mitis; Streptococcus mutans; Streptococcus oralis; Streptococcus sanguis; Streptococcus sobrinus; and the Streptococcus milleri group. The latter are often beta-hemolytic and commonly produce invasive pyogenic infections including brain and abdominal abscesses. Brain Abscess (commonly after dental procedures)
  • S. pneumoniae
  • S. bovis (associated with colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer)
• HACEK group:
  • Haemophilus
  • Actinobacillus (now known as Aggregatibacter)
  • Cardiobacterium
  • Eikenella
  • Kingella
• Other bacterial causes:
  • Enterococcus Enterococcus Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract. Enterococcus
  • Coxellia burnetii
  • Brucella Brucella Brucellosis (also known as undulant fever, Mediterranean fever, or Malta fever) is a zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly. Brucella/Brucellosis
  • Bartonella Bartonella Bartonella is a genus of gram-negative bacteria in the family Bartonellaceae. As a facultative intracellular parasite, Bartonella can infect healthy people as well as act as an opportunistic pathogen. Bartonella species are transmitted by vectors such as ticks, fleas, sandflies, and mosquitoes. B. henselae is the most common of the 3 species known to cause human disease. Bartonella
• Fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology:
  • Candida albicans Candida albicans A unicellular budding fungus which is the principal pathogenic species causing candidiasis (moniliasis). Candida/Candidiasis
  • Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins

Noninfective endocarditis Noninfective endocarditis Formation of a non-infectious thrombus, referred to as vegetation, on previously undamaged endocardium. It usually occurs as a complication of connective-tissue diseases and cancers because of the associated hypercoagulable state. Endocarditis etiologies^[10,11]

• Libman-Sacks endocarditis Libman-Sacks Endocarditis Systemic Lupus Erythematosus:
  • Due to circulating immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency
  • Associated with:
    • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
    • Antiphospholipid syndrome Antiphospholipid syndrome Antiphospholipid syndrome (APLS) is an acquired autoimmune disorder characterized by the persistent presence of antiphospholipid antibodies, which create a hypercoagulable state. These antibodies are most commonly discovered during a workup for a thrombotic event or recurrent pregnancy loss, which are the 2 most common clinical manifestations. Antiphospholipid Syndrome
  • Affects mitral > aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy
• Thrombotic (marantic) 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:
  • Malignancy Malignancy Hemothorax (due to metastases seeding Seeding The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation. Grading, Staging, and Metastasis the heart valves)
  • Hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States states
  • Chronic wasting disease
  • Chronic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (e.g., tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis)
• Rheumatic endocarditis Rheumatic endocarditis Endocarditis:
  • Due to antigen-antibody reaction after group A Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis
  • Affects mitral > aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy
• Löffler endocarditis Löffler endocarditis Endocarditis:
  • Associated with hypereosinophilic syndrome Hypereosinophilic syndrome A heterogeneous group of disorders with the common feature of prolonged eosinophilia of unknown cause and associated organ system dysfunction, including the heart, central nervous system, kidneys, lungs, gastrointestinal tract, and skin. There is a massive increase in the number of eosinophils in the blood, mimicking leukemia, and extensive eosinophilic infiltration of the various organs. Chronic Eosinophilic Leukemia
  • Due to eosinophilic infiltration and tissue damage
• 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 trauma to the cardiac valves
• Other autoimmune conditions (rare):
  • Behçet disease
  • Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
  • Systemic scleroderma Scleroderma Scleroderma (systemic sclerosis) is an autoimmune condition characterized by diffuse collagen deposition and fibrosis. The clinical presentation varies from limited skin involvement to diffuse involvement of internal organs. Scleroderma
  • 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

Risk Factors and Pathophysiology

Risk factors^[5,8–12]

The following are risk factors for IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis:

• Heart disease:
  • 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
  • Valvular abnormalities
  • Congenital defects
  • Presence of a prosthetic valve Prosthetic Valve Soft Tissue Abscess
• Age > 60 years
• IV drug use (most commonly affects the tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy)
• Poor dentition
• Implanted devices or catheters
• Immunosuppression
• Previous history of 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

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^[4,5,8,12]

• Predisposing factors:
  • Endocardial abnormality or injury
  • Bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
• Damaged endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology → platelet and fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis deposition → adherence by microorganisms
• Proliferation and invasion by organisms → inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → vegetation development → valve destruction
• Release of septic emboli → embolic complications and/or metastatic infection

Noninfective endocarditis Noninfective endocarditis Formation of a non-infectious thrombus, referred to as vegetation, on previously undamaged endocardium. It usually occurs as a complication of connective-tissue diseases and cancers because of the associated hypercoagulable state. Endocarditis^[10,11,20]

• Endothelial injury to the valve leaflets due to:
  • Trauma
  • Circulating immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency
  • Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response
  • Antigen-antibody reactions
• Platelet activation Platelet activation A series of progressive, overlapping events, triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. Hemostasis and deposition occurs (often during a hypercoagulable Hypercoagulable Hypercoagulable states (also referred to as thrombophilias) are a group of hematologic diseases defined by an increased risk of clot formation (i.e., thrombosis) due to either an increase in procoagulants, a decrease in anticoagulants, or a decrease in fibrinolysis. Hypercoagulable States state).
• Thrombus is interwoven with:
  • Fibrin Fibrin A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. Rapidly Progressive Glomerulonephritis
  • Immune complexes Immune complexes The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. C3 Deficiency
  • Mononuclear cells
• Vegetations are easily dislodged → embolic complications

Classification

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 can be further classified based on the clinical course, type of valve, and location.

By clinical course^[2,12,13]

Acute infectious endocarditis Acute infectious endocarditis Endocarditis:

• More sudden onset of symptoms
• Progresses more rapidly
• Larger vegetations
• More commonly affects normal valves
• Fatal if not treated promptly
• Most common cause is S. aureus S. aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Staphylococcus.

Subacute infectious endocarditis Subacute infectious endocarditis Endocardium infection that is usually caused by Streptococcus. Subacute infective endocarditis evolves over weeks and months with modest toxicity and rare metastatic infection. Endocarditis ( 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 lenta):

• More gradual onset of symptoms
• Progresses more slowly (weeks to months)
• Smaller vegetations
• More commonly affects congenitally abnormal or diseased valves
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may survive for months untreated.
• Most common cause is S. viridans.

By valve type^[1,5,13,22]

Native valve endocarditis Native valve endocarditis Endocarditis:

• Accounts for 78% of cases
• Further subdivided into:
  • Community acquired (most common)
  • Healthcare associated
  • IV drug use
• Most often associated with:
  • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus
  • Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus
  • HACEK organisms

Prosthetic valve Prosthetic Valve Soft Tissue Abscess 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:

• Further subdivided into:
  • Early:
    • < 60 days after valve placement
    • Often from contamination during surgery
    • Beware of antimicrobial-resistant organisms.
  • Intermediate: 60–365 days after valve placement
  • Late:
    • > 1 year after valve placement
    • Usually involves similar organisms to native valve endocarditis Native valve endocarditis Endocarditis
• Associated with a higher risk of complications and mortality Mortality All deaths reported in a given population. Measures of Health Status

By location^[2,4]

Left-sided endocarditis Left-sided endocarditis Endocarditis (more common):

• Mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy
• Aortic valve Aortic valve The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. Heart: Anatomy

Right-sided endocarditis Right-sided endocarditis Endocarditis (most common in IV drug use or with a right-sided cardiac anomaly or intravascular or cardiac implantable device):

• Tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy
• Pulmonic valve

Clinical Presentation

Presentation and course depend on the etiology, location of vegetations, and severity.

General signs and symptoms^[2,4,10]

The following are more frequently seen in IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis than NIE:

• 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 ( 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 should be suspected in a patient with a 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 of unknown origin)
• Night sweats Night sweats Tuberculosis
• 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
• Loss of appetite
• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
• Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus and arthralgias

Cardiac findings^[2,4,10]

• New or changed cardiac murmur:
  • Mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • Tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
• 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
• Arrhythmia:
  • Potentially due to spread of the infection and myocardial abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease formation
  • Results in disruption of the atrioventricular conduction system → conduction delay or heart block

Extracardiac findings^[2,12,13]

The following are potential findings in IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis:

• Splinter hemorrhages Splinter hemorrhages Endocarditis:
  • Small areas of red discoloration under the nails
  • Due to microemboli in capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology
• Osler nodes Osler nodes Endocarditis:
  • Painful red nodules on pads of the fingers and toes
  • Due to immune complex deposition and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
• Janeway lesions Janeway lesions Endocarditis:
  • Small, painless, erythematous lesions on the palms or soles
  • Due to septic emboli and microabscesses
• Roth spots Roth spots Endocarditis:
  • Red spots with pale centers on fundoscopic exam Fundoscopic Exam Head and Neck Examination
  • Due to retinal hemorrhages
• Petechiae Petechiae Primary Skin Lesions
• Conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy hemorrhage

Mnemonic

Signs of IE can be remembered with the mnemonic “FROM JANE”:

• Fever
• Roth spots
• Osler nodes
• Murmur
• Janeway lesions
• Anemia
• Nail bed hemorrhage
• Emboli

Systemic embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding^{[2,4,7,10,18]}

System embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding may occur in both IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis and NIE. Often, an embolic event is the only presenting evidence of NIE.

• Transient ischemic attack Transient ischemic attack Transient ischemic attack (TIA) is a temporary episode of neurologic dysfunction caused by ischemia without infarction that resolves completely when blood supply is restored. Transient ischemic attack is a neurologic emergency that warrants urgent medical attention. Transient Ischemic Attack (TIA) or stroke:
  • New focal deficit, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, encephalopathy Encephalopathy Hyper-IgM Syndrome, or change of consciousness
  • Can be a presenting symptom in 20% of IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis cases
  • Multiple emboli are common.
  • Ischemic stroke Ischemic Stroke An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke can undergo hemorrhagic transformation Transformation Change brought about to an organism’s genetic composition by unidirectional transfer (transfection; transduction, genetic; conjugation, genetic, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell’s genome. Bacteriology in up to 50% of cases.
  • An abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease can form in the infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage cavity.
• Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism:
  • 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
  • Pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Cough
  • Hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis
• Renal infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage:
  • Flank pain Flank pain Pain emanating from below the ribs and above the ilium. Renal Cell Carcinoma
  • Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
• Splenic emboli: LUQ pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways

Other complications^[2,4,7,10]

• Cardiac:
  • Perivalvular abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
  • Valve insufficiency
  • Valve rupture
  • 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)
  • Pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis → cardiac tamponade Tamponade Pericardial effusion, usually of rapid onset, exceeding ventricular filling pressures and causing collapse of the heart with a markedly reduced cardiac output. Pericarditis
• Renal:
  • Glomerulonephritis
  • Antibiotic-induced nephrotoxicity Nephrotoxicity Glycopeptides
• Metastatic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Splenic abscess Splenic Abscess Imaging of the Spleen
  • Mycotic aneurysm Mycotic aneurysm Aspergillus/Aspergillosis → cerebral hemorrhage
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease or meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Septic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
  • Osteomyelitis Osteomyelitis Osteomyelitis is an infection of the bone that results from the spread of microorganisms from the blood (hematogenous), nearby infected tissue, or open wounds (non-hematogenous). Infections are most commonly caused by Staphylococcus aureus. Osteomyelitis
  • Renal abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia or lung abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
• Death: mortality Mortality All deaths reported in a given population. Measures of Health Status rate up to 40%

Diagnosis

Echocardiogram Echocardiogram Transposition of the Great Vessels^{[2,15,16,22,23]}

Obtain an echocardiogram Echocardiogram Transposition of the Great Vessels as soon as 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 is suspected (within 12 hours of evaluation).

• Transthoracic echo ( TTE TTE Imaging of the Heart and Great Vessels):
  • Used as an initial screening Screening Preoperative Care tool
  • A negative study does not exclude the diagnosis.
  • Has sensitivity of 75% for detecting vegetations
• Transesophageal echo ( 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):
  • More sensitive, but more invasive
  • Should be performed if TTE TTE Imaging of the Heart and Great Vessels is negative and suspicion for 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 is high
  • Increased sensitivity for vegetations to 85%–90% when used with TTE TTE Imaging of the Heart and Great Vessels
  • Should be performed for all cases of suspected prosthetic valve Prosthetic Valve Soft Tissue Abscess or pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias 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 and when an abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease is suspected
  • If negative, repeat 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 in 3–5 days after initial 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 (or earlier if clinical changes occur) if high suspicion persists.
• Findings:
  • Valvular vegetations:
    • Size
    • Mobility
    • Calcifications
  • Complications:
    • Valvular insufficiency
    • Abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
• Cannot determine the cause of vegetations ( IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis versus NIE)

Supporting workup^{[2,12,13,15–17,20,23]}

Laboratory findings:

• The following are nonspecific but may signal IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis:
  • Blood cultures:
    • 3 sets should be obtained from different sites.
    • Must be obtained prior to starting antibiotics
    • Negative cultures do not rule out IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis.
    • Blood cultures may be negative in approximately 10% of 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 cases.
    • Most common reason for negative cultures is prior antibiotic use.
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus and polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR):
    • Consider pursuing if cultures are negative
    • Useful for fastidious Fastidious Bordetella organisms that are difficult to isolate (Coxiella, Bartonella Bartonella Bartonella is a genus of gram-negative bacteria in the family Bartonellaceae. As a facultative intracellular parasite, Bartonella can infect healthy people as well as act as an opportunistic pathogen. Bartonella species are transmitted by vectors such as ticks, fleas, sandflies, and mosquitoes. B. henselae is the most common of the 3 species known to cause human disease. Bartonella, Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia, Tropheryma Tropheryma A genus of gram-positive bacteria in the family cellulomonadaceae. Whipple’s Disease, Brucella Brucella Brucellosis (also known as undulant fever, Mediterranean fever, or Malta fever) is a zoonotic infection that spreads predominantly through ingestion of unpasteurized dairy products or direct contact with infected animal products. Clinical manifestations include fever, arthralgias, malaise, lymphadenopathy, and hepatosplenomegaly. Brucella/Brucellosis, Legionella Legionella Legionella is a facultative intracellular, gram-negative bacilli. Legionella does not grow on common culture media because it requires certain supplementation (cysteine and iron). Legionella pneumophila (L. pneumophila) accounts for the majority of human infections. Legionella/Legionellosis, and Aspergillus Aspergillus A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family trichocomaceae. Echinocandins spp.)
  • CBC:
    • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus with left shift Left Shift Yersinia pestis/Plague
    • Normocytic anemia Normocytic Anemia Anemia: Overview and Types
  • Inflammatory markers:
    • ↑ Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess
    • ↑ C-reactive protein (CRP)
• The following may be useful in NIE:
  • Antinuclear antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
  • Lupus anticoagulant Lupus anticoagulant An antiphospholipid antibody found in association with systemic lupus erythematosus, antiphospholipid syndrome; and in a variety of other diseases as well as in healthy individuals. In vitro, the antibody interferes with the conversion of prothrombin to thrombin and prolongs the partial thromboplastin time. In vivo, it exerts a procoagulant effect resulting in thrombosis mainly in the larger veins and arteries. It further causes obstetrical complications, including fetal death and spontaneous abortion, as well as a variety of hematologic and neurologic complications. Antiphospholipid Syndrome
  • Antiphospholipid antibodies Antiphospholipid antibodies Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome; related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. Antiphospholipid Syndrome
  • Coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies to identify DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation ( disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation)

Imaging:

• 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):
  • Generally normal unless there is extension Extension Examination of the Upper Limbs of the infection
  • A baseline tracing should be performed in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Possible findings:
    • Heart block or atrioventricular dissociation Dissociation Defense Mechanisms
    • Bundle branch block Bundle branch block A form of heart block in which the electrical stimulation of heart ventricles is interrupted at either one of the branches of bundle of His thus preventing the simultaneous depolarization of the two ventricles. Bundle Branch and Fascicular Blocks
• 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:
  • Can rule out other causes of symptoms
  • Potential findings in 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:
    • Septic emboli to the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
    • 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 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
• CT:
  • Can be used to assess for sites of metastatic infection
  • May be useful if an underlying malignancy Malignancy Hemothorax is suspected (for NIE)
  • Cardiac CT can be used to better delineate valvular anatomy as well as to evaluate 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 if surgical intervention is planned.
  • A good alternative to coronary angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery (which may risk vegetation dislodgement and embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding)
• Cardiac MRI Cardiac MRI Imaging of the Heart and Great Vessels:
  • May be especially useful for NIE, in which vegetations may be small and friable and not picked up 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)
  • May be able to differentiate IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis from NIE based on the pattern of emboli distribution
• Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification MRI: performed if cerebral embolic events are suspected (obtain with vascular imaging or MRA MRA Imaging of the Heart and Great Vessels to check for mycotic aneurysm Mycotic aneurysm Aspergillus/Aspergillosis)

Duke diagnostic criteria^[16,22,23]

The Duke diagnostic criteria is a set of clinical criteria that can aid in the diagnosis of IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis.

• Must meet 1 of the following for a definitive diagnosis of IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis:
  • 2 major criteria
  • 1 major plus 3 minor criteria
  • 5 minor criteria
• Major criteria:
  • Positive blood cultures (1 of the following):
    • Typical organism for IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis in 2 separate blood cultures
    • Persistently positive cultures
    • Single positive culture for Coxiella burnetii Coxiella burnetii A species of gram-negative bacteria that grows preferentially in the vacuoles of the host cell. It is the etiological agent of q fever. Coxiella/Q Fever
  • Findings of endocardial involvement 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) (1 of the following):
    • Mobile echodense masses attached to valvular leaflets or endocardium Endocardium The innermost layer of the heart, comprised of endothelial cells. Heart: Anatomy
    • Periannular abscesses
    • New dehiscence of a valvular prosthesis
    • New valvular regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
• Minor criteria:
  • 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 > 38°C (100.4°F)
  • Risk factors:
    • IV drug use
    • Predisposing heart condition (e.g., prosthetic heart valve, regurgitant valvular lesion)
  • Vascular findings:
    • Major arterial emboli
    • Janeway lesions Janeway lesions Endocarditis
    • Conjunctival hemorrhages
    • Septic infarcts
    • Mycotic aneurysm Mycotic aneurysm Aspergillus/Aspergillosis
  • Immunologic findings:
    • Osler nodes Osler nodes Endocarditis
    • Roth spots Roth spots Endocarditis
    • Glomerulonephritis
  • Microbiologic findings by culture that do not meet major criteria
• Cases that may not be reliably diagnosed by Duke criteria:
  • Pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias 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
  • Prosthetic valve Prosthetic Valve Soft Tissue Abscess 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
  • Blood-culture–negative 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

Management

Medical management of IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis^[14–17,23]

Prompt initiation of IV antibiotics is necessary if the patient is acutely ill. However, blood cultures should be obtained prior to the start of antibiotic therapy. The recovery rate of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology is diminished by 40% when antibiotics are administered prior to obtaining blood cultures.

• Recommended consultations:
  • Infectious disease
  • Cardiology
  • Cardiothoracic surgery
• Empiric antibiotic therapy options: generally cover staphylococci (MSSA and MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus), streptococci, and enterococci^[15]
  • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins + gentamicin Gentamicin Aminoglycosides + nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS) or oxacillin (or flucloxacillin in Europe):
    • Ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins 2 g IV every 4 hours
    • Gentamicin Gentamicin Aminoglycosides 3 mg/kg/dose IV (dosing adjusted per protocol) 
    • Nafcillin Nafcillin A semi-synthetic antibiotic related to penicillin. Staphylococcal Scalded Skin Syndrome (SSSS) or oxacillin (or flucloxacillin) 2 g IV every 4 hours
  • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides + gentamicin Gentamicin Aminoglycosides (if allergic to penicillin Penicillin Rheumatic Fever)
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 30 mg/kg/day IV in 2 divided doses (dosing adjusted per protocol to achieve trough concentration of 10–20 μg/mL) 
    • Gentamicin Gentamicin Aminoglycosides 3 mg/kg/dose IV (in 1 dose or 3 divided doses (dosing adjusted to achieve trough concentration of < 1 µg/mL) 
  • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides + gentamicin Gentamicin Aminoglycosides + rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis  for early (< 1 year) prosthetic valve Prosthetic Valve Soft Tissue Abscess or healthcare-associated 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:
    • Vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 30 mg/kg/day IV in 2 divided doses (dosing adjusted per protocol to achieve trough concentration of 10–20 μg/mL) 
    • Gentamicin Gentamicin Aminoglycosides 3 mg/kg/dose IV (dosing adjusted to achieve trough concentration of < 1 µg/mL) 
    • Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis 900–1200 mg/day IV or orally in 3 divided doses
• Tailor antibiotics or antifungals based on:
  • Identified pathogen
  • Sensitivities
• Repeat blood cultures every 24–48 hours until negative.
• Duration of therapy: 6 weeks
  • 0 to 2 weeks: inpatient ( critical phase Critical phase Dengue Virus, when complications occur)
  • > 2 weeks: Outpatient parenteral antibiotic therapy can be considered, except in cases of 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), worrisome echocardiographic findings, renal impairment, or neurologic signs.

Medical management of NIE^[19,20]

• Treatment for the underlying disorder
• Anticoagulation Anticoagulation Pulmonary Hypertension Drugs (unfractionated or low-molecular-weight heparin)

Surgical management^[18]

• Indications:
  • Valve repair or replacement is indicated for:
    • 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)
    • Persistent infection
    • Embolic events
    • Prosthetic valve Prosthetic Valve Soft Tissue Abscess dehiscence
    • Perivalvular abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
    • Conduction abnormalities
  • Implanted hardware removal (e.g., pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias) is indicated if:
    • Definite lead or hardware infection
    • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock
    • Pocket infection
    • Persistent bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
  • Mycotic aneurysms:
    • To rule out a mycotic aneurysm Mycotic aneurysm Aspergillus/Aspergillosis, catheter angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery should be performed if there is intracranial hemorrhage Intracranial hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most sahs originate from a saccular aneurysm in the circle of willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage in the setting of IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis.
    • Mycotic aneurysms should be repaired if they expand despite antibiotic therapy.
• Timing:
  • > 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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 will need valve surgery.
    • The majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will require it within the active phase (while still on antibiotics).
    • Some may require it emergently (1st 24–48 hours).
  • In the presence of ischemic or hemorrhagic stroke Hemorrhagic stroke Stroke due to rupture of a weakened blood vessel in the brain (e.g., cerebral hemispheres; cerebellum; subarachnoid space). Subarachnoid Hemorrhage, valve replacement/repair should ideally be delayed for 4 weeks.
  • If there is a decline in cardiac function, recurrent stroke, systemic embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding, or uncontrolled infection despite antibiotics, delay may not be feasible.

Prevention^[21,24,25]

• Prophylaxis Prophylaxis Cephalosporins is recommended for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
  • With cardiac conditions that have increased adverse outcomes from IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis, AND 
  • Are undergoing procedures that highly predispose them to bacteremia Bacteremia The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. Glycopeptides
• Pre-procedure antibiotics:
  • Routine IE IE Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis prophylaxis Prophylaxis Cephalosporins is not recommended in all oral/dental, respiratory tract, gastrointestinal (GI), genitourinary (GU), or dermatologic procedures.
  • Assess the risk associated with the procedure and review the cardiac condition(s) of the patient.
  • High-risk procedures:
    • Dental procedures involving manipulation of the gingiva or mucosa (e.g., tooth extraction, periodontal surgery)
    • Respiratory tract procedures involving manipulation of mucosa (e.g., invasive procedure to treat or drain an infection, such as an abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease or empyema Empyema Presence of pus in a hollow organ or body cavity. Pneumonia)
    • Procedures involving infected or colonized sites (e.g., infected skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions structure, urgent invasive intervention in an infected site)
    • Implantation Implantation Endometrial implantation of embryo, mammalian at the blastocyst stage. Fertilization and First Week of cardiac electronic device
  • Prophylaxis Prophylaxis Cephalosporins indicated for:
    • Prosthetic valves
    • Unrepaired cyanotic congenital heart disease
    • Repaired congenital heart defect with prosthetic material
    • Prior episode of 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
    • Transplanted heart with valvulopathy
• Complete treatment for active infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Proper dental hygiene
• Avoid IV drug abuse

Differential Diagnosis

• Cardiac myxoma Myxoma A benign neoplasm derived from connective tissue, consisting chiefly of polyhedral and stellate cells that are loosely embedded in a soft mucoid matrix, thereby resembling primitive mesenchymal tissue. It occurs frequently intramuscularly where it may be mistaken for a sarcoma. It appears also in the jaws and the skin. Cardiac Myxoma: a benign Benign Fibroadenoma tumor Tumor Inflammation and the most common of the primary tumors of the adult heart. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may develop signs and symptoms of valvular obstruction, thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus, and arrhythmias. Diagnosis is made 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), cardiac MRI Cardiac MRI Imaging of the Heart and Great Vessels, or cardiac CT. Complete surgical excision is required because of the substantial risk of embolization Embolization A method of hemostasis utilizing various agents such as gelfoam, silastic, metal, glass, or plastic pellets, autologous clot, fat, and muscle as emboli. It has been used in the treatment of spinal cord and intracranial arteriovenous malformations, renal arteriovenous fistulas, gastrointestinal bleeding, epistaxis, hypersplenism, certain highly vascular tumors, traumatic rupture of blood vessels, and control of operative hemorrhage. Gastrointestinal Bleeding and cardiovascular complications, including sudden death.
• Prosthetic valve Prosthetic Valve Soft Tissue Abscess thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus: insufficient anticoagulation Anticoagulation Pulmonary Hypertension Drugs after a prosthetic valve Prosthetic Valve Soft Tissue Abscess is implanted can lead to thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus of the valve, which places the patient at risk of thromboembolism Thromboembolism Obstruction of a blood vessel (embolism) by a blood clot (thrombus) in the blood stream. Systemic Lupus Erythematosus and valvular stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) or regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD), leading to 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). The diagnosis is made based on the clinical history 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). Management varies, but may include thrombolytic therapy, appropriate anticoagulation Anticoagulation Pulmonary Hypertension Drugs, and potential 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.
• Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism: obstruction of the pulmonary 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, most often due to thrombus migration from the deep venous system. Signs and symptoms include pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, 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, tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, and 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. Severe cases can result in hemodynamic instability or cardiopulmonary arrest Cardiopulmonary arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest. A chest CT with angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery is the primary method of diagnosis. Management includes oxygenation, anticoagulation Anticoagulation Pulmonary Hypertension Drugs, and thrombolytic therapy for unstable patients Unstable Patients Blunt Chest Trauma.
• Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the heart muscle that can be infectious or noninfectious in etiology. The presentation varies but can include signs and symptoms of 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) and cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock. Echocardiogram Echocardiogram Transposition of the Great Vessels may show global systolic dysfunction Systolic dysfunction Dilated Cardiomyopathy, cardiac MRI Cardiac MRI Imaging of the Heart and Great Vessels will show edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, and endomyocardial biopsy Endomyocardial biopsy Myocarditis can give a definitive diagnosis. Treatment focuses on management of 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) and the underlying cause.
• Pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the outer lining of the heart resulting from infection, autoimmune disease, radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, surgery, or 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. Pericarditis Pericarditis Pericarditis is an inflammation of the pericardium, often with fluid accumulation. It can be caused by infection (often viral), myocardial infarction, drugs, malignancies, metabolic disorders, autoimmune disorders, or trauma. Acute, subacute, and chronic forms exist. Pericarditis clinically presents with 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, pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways that increases with lying supine, and a pericardial rub on auscultation. An 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) with diffuse ST-segment elevation and an echo showing a 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 can confirm the diagnosis. Management is supportive.