Myocarditis (Clinical)

Overview

Definition

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 is an inflammatory disease of the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy.

Epidemiology^[5,11]

• 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: approximately 10–22 cases per 100,000 people (2013)^[19]
• Global burden is difficult to estimate; 6.1 per 100,000 (2019)^[16]
• About 1%–5% of viral 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 involve the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy.
• Affects more men than women
• More common in young adults

Etiology^[2,10,11]

The most frequent causes of 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 are presumed viral 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, cardiotoxins such as those found in chemotherapy Chemotherapy Osteosarcoma regimens and recreational drugs, and immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs activation.

• Idiopathic Idiopathic Dermatomyositis (50% of cases)
• Infectious organisms:
  • Viral (most common in North America and Europe):
    • Most common cause of lymphocytic 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 in North America and Europe
    • Still controversial whether SARS-CoV-2 infection is causative (or if immune-mediated)^[18]
  • Bacterial
  • Protozoal (most common in Africa, Asia ASIA Spinal Cord Injuries, and South America): Chagas disease Chagas disease Infection with the protozoan parasite trypanosoma cruzi, a form of trypanosomiasis endemic in central and south america. It is named after the brazilian physician carlos chagas, who discovered the parasite. Infection by the parasite (positive serologic result only) is distinguished from the clinical manifestations that develop years later, such as destruction of parasympathetic ganglia; chagas cardiomyopathy; and dysfunction of the esophagus or colon. Trypanosoma cruzi/Chagas disease caused by Trypanosoma cruzi Trypanosoma cruzi Chagas disease is an infection caused by the American trypanosome Trypanosoma cruzi. This parasitic protozoan is transmitted in the feces of reduviid bugs in South and Central America. Acute infection may present with inflammation at the inoculation site (chagoma), fever, and lymphadenopathy. Untreated, chronic infection can progress to severe complications. Trypanosoma cruzi/Chagas disease is the most common infective cause worldwide; endemic in rural South and Central America
  • Fungal
• Immune-mediated disorders:^[10]
  • Rheumatic fever Rheumatic fever Acute rheumatic fever (ARF) is an autoimmune inflammatory process that usually follows Streptococcal pharyngitis. Acute rheumatic fever usually occurs 2-4 weeks after an untreated infection and affects the heart, skin, joints, and nervous system. Rheumatic Fever
  • Allergic reactions Allergic Reactions Type I hypersensitivity reaction against plasma proteins in donor blood Transfusion Reactions
  • Transplant rejection
  • Kawasaki disease Kawasaki disease An acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes in infants and young children. The principal symptoms are fever, congestion of the ocular conjunctivae, reddening of the lips and oral cavity, protuberance of tongue papillae, and edema or erythema of the extremities. Kawasaki Disease
  • Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
  • 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
  • Polymyositis Polymyositis Polymyositis (PM) is an autoimmune inflammatory myopathy caused by T cell-mediated muscle injury. The etiology of PM is unclear, but there are several genetic and environmental associations. Polymyositis is most common in middle-aged women and rarely affects children. Polymyositis
  • Dermatomyositis Dermatomyositis A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. Paraneoplastic Syndromes
  • 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
  • Juvenile idiopathic Idiopathic Dermatomyositis arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis
  • 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
• Exogenous agents:^[13–15]
  • Smallpox Smallpox An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. Orthopoxvirus vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination (subclinical, 1:200; clinically suspected, 1:5,500)
  • Rare after COVID-19 COVID-19 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly affects the respiratory system but can also cause damage to other body systems (cardiovascular, gastrointestinal, renal, and central nervous systems). mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination or tetanus Tetanus Tetanus is a bacterial infection caused by Clostridium tetani, a gram-positive obligate anaerobic bacterium commonly found in soil that enters the body through a contaminated wound. C. tetani produces a neurotoxin that blocks the release of inhibitory neurotransmitters and causes prolonged tonic muscle contractions. Tetanus toxoid Toxoid Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are tropanes found in cyanobacteria. Vaccination
• Genetic predisposition:
  • Genetic defects in the structural proteins Structural proteins Proteins and Peptides of myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology
  • ↑ Susceptibility to myocyte damage
• Environmental causes:
  • Exposure to carbon monoxide Carbon monoxide Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. Carbon Monoxide Poisoning or phosphorus
  • Heavy metal toxicity Toxicity Dosage Calculation (e.g., arsenic Arsenic A shiny gray element with atomic symbol as, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the fourth annual report on carcinogens, arsenic and certain arsenic compounds have been listed as known carcinogens. Metal Poisoning (Lead, Arsenic, Iron))
  • Black widow venom
  • Scorpion and snake Snake Limbless reptiles of the suborder serpentes. Snakebites bites
• Drugs:
  • Doxorubicin
  • Cyclophosphamide Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It has been used in the treatment of lymphoma and leukemia. Its side effect, alopecia, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. Immunosuppressants
  • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • Amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants
  • Ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism
  • Antibiotics:
    • Penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins
    • Cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins
    • Sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim
  • Immune therapies:
    • Trastuzumab Trastuzumab A humanized monoclonal antibody against the ErbB-2 receptor (HER2). As an antineoplastic agent, it is used to treat breast cancer where HER2 is overexpressed. Targeted and Other Nontraditional Antineoplastic Therapy
    • Interferon
    • Interleukin-2 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-lymphocytes which induces DNA synthesis in naive lymphocytes. Interleukins
  • Novel cancer therapies/ immune checkpoint inhibitors Immune Checkpoint Inhibitors Drugs that block negative regulator immune checkpoint proteins (e.g., PD-1 receptor and CTLA-4 antigen) thereby increasing suppressed immune activation in immunotherapies. Cancer Immunotherapy:
    • Pembrolizumab Pembrolizumab Squamous Cell Carcinoma (SCC)
    • Nivolumab Nivolumab A genetically engineered, fully humanized immunoglobulin g4 monoclonal antibody that binds to the pd-1 receptor, activating an immune response to tumor cells. It is used as monotherapy or in combination with ipilimumab for the treatment of advanced malignant melanoma. It is also used in the treatment of advanced or recurring non-small cell lung cancer; renal cell carcinoma; and Hodgkin’s lymphoma. Melanoma
    • Ipilimumab
    • Atezolizumab
    • Avelumab
    • Durvalumab

Infectious causes of infectious myocarditis Infectious myocarditis Myocarditis^[2,10,11]

The following table summarizes the infectious causes of 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. Keep in mind that this list is not exhaustive.

Pathophysiology

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 due to various etiologies leads to enlargement of the heart and dilation of all chambers.^[1,2,11,17]

• Causes of myocyte injury:
  • Viral: direct viral toxicity Toxicity Dosage Calculation, lymphocytic infiltration, and 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
  • Bacterial: direct invasion or bacterial toxins
  • Autoimmune: autoantibodies Autoantibodies Antibodies that react with self-antigens (autoantigens) of the organism that produced them. Blotting Techniques to myocyte components
  • Toxins: hypersensitivity or direct effects
• Myocardial 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 and injury (T and B lymphocytes B lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions) → myocardial necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
• Severe and prolonged damage → fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans → chamber remodeling → dilated cardiomyopathy Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is the most common type of non-ischemic cardiomyopathy and a common cause of heart failure (HF). The cause may be idiopathic, familial, or secondary to a variety of underlying conditions. The disease is characterized by the enlargement of 1 or both ventricles and reduced systolic function. Dilated Cardiomyopathy
• Consequences:
  • 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)
  • Cardiac arrhythmia
  • Extension Extension Examination of the Upper Limbs to the pericardium Pericardium A conical fibroserous sac surrounding the heart and the roots of the great vessels (aorta; venae cavae; pulmonary artery). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers. Heart: Anatomy → 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

Clinical Presentation

The clinical presentation can vary based on the severity and temporal progression of symptoms. Most signs and symptoms are related 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) in fulminant 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.

Classification^[1,17]

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 is classified based on temporal progression.

• Subclinical: absent or minimal symptoms
• Acute: 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) develops in < 3 months.
• Chronic: 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) develops in > 3 months.

Symptoms^[3,11]

• 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 and rash Rash Rocky Mountain Spotted Fever may signify eosinophilic 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.
• 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
• Orthopnea Orthopnea Pulmonary Edema
• Loss of appetite
• Abdominal pain Abdominal Pain Acute Abdomen
• 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
• Decreased exercise tolerance Tolerance Pharmacokinetics and Pharmacodynamics

Physical exam^[4,11]

Recognize signs of right 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) including right upper quadrant Right upper quadrant Anterior Abdominal Wall: Anatomy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.

• 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
• Peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema
• Hepatomegaly
• Pulmonary rales Rales Respiratory Syncytial Virus
• Jugular venous distention
• Murmur → may indicate chamber enlargement:
  • Mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • Tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
• S3 S3 Heart Sounds and S4 S4 Heart Sounds gallops
• Pericardial friction rub Pericardial friction rub A rasping, scratching, or grating sound with up to 3 components per cardiac cycle and best heard during expiration with the patient leaning forward. Pericarditis ( 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)

Complications^[3,11,17]

• Cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock
• 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
• Dilated cardiomyopathy Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is the most common type of non-ischemic cardiomyopathy and a common cause of heart failure (HF). The cause may be idiopathic, familial, or secondary to a variety of underlying conditions. The disease is characterized by the enlargement of 1 or both ventricles and reduced systolic function. Dilated Cardiomyopathy
• Cardiac arrhythmias
• Mural thrombus Mural thrombus Myocardial Infarction with systemic emboli
• Sudden cardiac arrest Cardiac 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

Diagnosis

Initial evaluation^[9,10]

The European Society of Cardiology (ESC) and the American Heart Association American Heart Association A voluntary organization concerned with the prevention and treatment of heart and vascular diseases. Heart Failure (AHA) scientific statements recommend measuring the erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess ( ESR ESR Soft Tissue Abscess) and C-reactive protein (CRP) and troponin levels to help diagnose 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; however, a normal level for any of these does not exclude 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.

Laboratory studies:^[9,10,12]

• ↑ Erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Soft Tissue Abscess
• ↑ CRP
• ↑ Troponin and CK
• ↑ 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 natriuretic peptide ( BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation): useful prognostically
• Order in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with suspected 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:
  • CBC with differential count
  • Chemistries
  • Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests
  • Arterial blood gas Arterial blood gas Respiratory Alkalosis (ABG)
• Blood cultures if febrile
• Peripheral eosinophilia Eosinophilia Abnormal increase of eosinophils in the blood, tissues or organs. Autosomal Dominant Hyperimmunoglobulin E Syndrome > 65% seen with hypersensitivity/eosinophilic 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
• ↑ Lactate level: impending circulatory failure
• Viral testing may aid in identifying the causative agent; routine viral serologies are not recommended (low sensitivity and specificity Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. Epidemiological Values of Diagnostic Tests compared to PCR PCR 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) on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma tissue).
• Rheumatologic screening Screening Preoperative Care for autoimmune causes

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):^[9,10,12]

• ST changes:
  • Often nonspecific
  • Diffuse ST elevation signals seen in 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, often in a nonvascular distribution.
  • Injury with ST-segment elevations in segmental contiguous leads may mimic acute coronary artery Coronary Artery Truncus Arteriosus occlusion.
• PR prolongation or PR-segment depression: may be seen with concomitant evidence of 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
• Arrhythmia
• Conduction delays (e.g., QRS prolongation)
• Low QRS voltage with fulminant 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 because of myocardial 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

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:^[3,12]

• Nonspecific; normal to enlarged heart
• Indications 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):
  • Pulmonary venous congestion
  • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion

Cardiac imaging^[9,17]

Echocardiogram Echocardiogram Transposition of the Great Vessels:

• 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 with suspected 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
• May be normal in early or mild disease
• Possible findings:
  • Left ventricular dilation:
    • Greater dilation suggests a chronic insult.
    • Small left ventricle suggests a fulminant pathogenesis.
  • Ventricular systolic dysfunction Systolic dysfunction Dilated Cardiomyopathy
  • Mitral or tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
  • 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
  • Intracardiac Intracardiac Total Anomalous Pulmonary Venous Return (TAPVR) thrombi
  • Increased wall thickness
  • Segmental hypokinesia
  • Abnormal myocardial echogenicity
• Excludes other causes 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)

Cardiac MRI Cardiac MRI Imaging of the Heart and Great Vessels:

• Characteristic enhancement of the myocardial wall
• Myoca
• Indicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with clinically suspected 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
• An accurate noninvasive tool used to detect myocardial 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 and replacement fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
• Also considered the gold standard to quantify:
  • Biventricular volumes
  • Ejection fraction Ejection fraction Cardiac Cycle
  • Cardiac mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
• Characterizes acute myocarditis Acute myocarditis Myocarditis with tissue-level pathologies:
  • 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 or scar Scar Dermatologic Examination
  • Fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
  • Characteristic gadolinium Gadolinium An element of the rare earth family of metals. It has the atomic symbol gd, atomic number 64, and atomic weight 157. 25. Its oxide is used in the control rods of some nuclear reactors. Magnetic Resonance Imaging (MRI) enhancement of the myocardial wall
  • Myocardial 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
  • Myocardial hyperemia
• Used for follow-up as well; performed 6–12 months after the index event
• rdial 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
• Myocardial hyperemia

Other imaging:

• Positron emission tomography ( PET PET An imaging technique that combines a positron-emission tomography (PET) scanner and a ct X ray scanner. This establishes a precise anatomic localization in the same session. Nuclear Imaging):
  • Rarely used
  • Alternative tool when:
    • Cardiac MRI Cardiac MRI Imaging of the Heart and Great Vessels contraindicated
    • Systemic autoimmune disease suspected (and there is extracardiac involvement), especially cardiac sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
• Invasive coronary angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery:
  • Often performed to rule out acute coronary syndrome (ACS), especially in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at high risk for ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease
  • Additionally, the most common cause of elevated cardiac biomarkers is ACS, so there is a low threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction for performing this test.

Endomyocardial biopsy Endomyocardial biopsy Myocarditis

Endomyocardial biopsy Endomyocardial biopsy Myocarditis (EMB) is the gold standard for diagnosis; however, it is rarely needed. According to the AHA, the American College of Cardiology (ACC), and the ESC, in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with rapidly progressing 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 cause can be confirmed only by myocardial histology, as with 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), EMB should be considered.^[9]

Indications:

• Acute deterioration of cardiac function without a known etiology
• Failure to respond to therapy within 1–2 weeks after diagnosis
• New-onset 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) associated with a dilated left ventricle (LV) and new ventricular arrhythmia or bradyarrhythmia Bradyarrhythmia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias 
• Suspected hypersensitivity (subset of eosinophilic) 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 
• Fulminant 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 when MRI is not possible

Major histopathologic types (on biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma):^[1]

• Lymphocytic 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 (most common)
• Neutrophilic 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
• Eosinophilic 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 
• Giant cell 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
• Cardiac sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
• Other granulomatous 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

Findings:

• Cellular infiltrates may be:
  • Lymphocytic
  • Eosinophilic
  • Neutrophilic
  • Mononuclear
• Myocyte necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
• Interstitial fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
• Myofiber 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
• Granulomatous changes:
  • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium
  • 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
  • Parasitic
  • Sarcoid myocarditis Sarcoid myocarditis Myocarditis (noncaseating)
• Giant cells Giant cells Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In aids, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. Giant Cell Arteritis: giant-cell myocarditis Giant-cell myocarditis Myocarditis (a rapidly progressive necrotizing myocardial destruction, implying worse 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)

Management

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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 presenting with 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 are often young and have no prior cardiac disease and are thus treated with IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids, which can cause worsening of acute 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. Early invasive hemodynamic monitoring and right-sided heart catheterization are indicated if 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 is suspected.

General principles^[9,12,17]

• Management for 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 is generally supportive but often includes:
  • 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) management
  • Arrhythmia management
  • Treating the underlying etiology (when possible)
• Referral to cardiology for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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:
  • Myocardial dysfunction may worsen.
  • Intervention may be needed.
  • Transfer to a tertiary care center with ventricular support devices available.
  • Consider transfer to a facility with transplantation available if early signs of fulminant 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 are present.
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with 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 due to toxic agents can be monitored safely if:
  • Ejection fraction Ejection fraction Cardiac Cycle remains > 40% 
  • No 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)
• Most cases resolve spontaneously.
• Treat 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 associated with a condition (e.g., autoimmune disease, Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease) according to standard guidelines.

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) management^[9,12,17]

The 1st-line treatment of 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 is 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 and diuresis. Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will require inotropic support or mechanical assist devices. Cardiac transplantation may be needed for intractable 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) (HF).

Medical therapy 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):

• Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
• ACE inhibitors ACE inhibitors Truncus Arteriosus
• Beta blockers
• 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
• Aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Angina Medication

For fulminant 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):

• Vasopressor Vasopressor Acute Cholangitis therapy with norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS
• Inotropic support
• Intraaortic balloon pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols
• Left ventricular assist device
• Cardiac transplantation

Role of immunosuppression:^[17,20–22]

• Not for acute infectious myocarditis Infectious myocarditis Myocarditis
• Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
  • Beneficial for:
    • Eosinophilic 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
    • Lymphocytic 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 
    • Immune checkpoint inhibitor–associated 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
    • Giant cell 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
    • Cardiac sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis
  • Glucocorticoid dosing: solumedrol 1 g IV for 3 days, then oral prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants 1–2 mg/kg daily for a few months (no clear dose established). Slow weaning Weaning Techniques for effecting the transition of the respiratory-failure patient from mechanical ventilation to spontaneous ventilation, while meeting the criteria that tidal volume be above a given threshold (greater than 5 ml/kg), respiratory frequency be below a given count (less than 30 breaths/min), and oxygen partial pressure be above a given threshold (pao2 greater than 50mm hg). Weaning studies focus on finding methods to monitor and predict the outcome of mechanical ventilator weaning as well as finding ventilatory support techniques which will facilitate successful weaning. Present methods include intermittent mandatory ventilation, intermittent positive pressure ventilation, and mandatory minute volume ventilation. Invasive Mechanical Ventilation over 1 year has been recommended.
  • In some cases, combined with other agents (e.g. azathioprine Azathioprine An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the fourth annual report on carcinogens, this substance has been listed as a known carcinogen. Immunosuppressants)
• IV immune globulin: insufficient data supporting routine use in acute myocarditis Acute myocarditis Myocarditis
• In giant cell 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:
  • Cases respond to immunosuppressive therapy (suggesting that the condition is mostly autoimmune, and not an active infection).
  • Antithymocyte globulin and calcineurin inhibitor Calcineurin inhibitor Compounds that inhibit or block the phosphatase activity of calcineurin. Vitiligo therapy have been found to be beneficial in giant cell 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 and can lead to clinical remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches in ⅔ of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Above treatment is given with corticosteroids Corticosteroids Chorioretinitis and cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants.

Arrhythmia management^[9,12,17]

• Antiarrhythmic therapy
• Avoid treatment of sinus 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 with negative inotropic rate-control agents:
  • Metoprolol Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat angina pectoris; hypertension; and cardiac arrhythmias. Antiadrenergic Drugs
  • Diltiazem Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of calcium ion on membrane functions. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
  • Verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs
• Cardioversion Cardioversion Atrial Fibrillation
• Temporary or permanent pacing
• Implantable cardiac defibrillator Defibrillator Cardiac electrical stimulators that apply brief high-voltage electroshocks to the heart. These stimulators are used to restore normal rhythm and contractile function in hearts of patients who are experiencing ventricular fibrillation or ventricular tachycardia that is not accompanied by a palpable pulse. Some defibrillators may also be used to correct certain noncritical dysrhythmias (called synchronized defibrillation or cardioversion), using relatively low-level discharges synchronized to the patient’s ECG waveform. Cardiac Arrest (ICD): recommended for giant cell 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 owing to a high risk of ventricular 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

Other considerations^[5,7,8]

• Anticoagulants Anticoagulants Anticoagulants are drugs that retard or interrupt the coagulation cascade. The primary classes of available anticoagulants include heparins, vitamin K-dependent antagonists (e.g., warfarin), direct thrombin inhibitors, and factor Xa inhibitors. Anticoagulants are indicated for:
  • Intracardiac Intracardiac Total Anomalous Pulmonary Venous Return (TAPVR) thrombi
  • Evidence of systemic embolism
  • 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
• Avoidance of:
  • NSAIDs NSAIDS Primary vs Secondary Headaches
  • Alcohol consumption
  • Exercise

Long term follow-up^[9,12,17]

Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have a partial or full recovery. However, long-term follow-up and monitoring are recommended.

• Gradual resumption of physical activities:
  • No competitive sports for 3–6 months (risk of ventricular arrhythmias)
  • AHA recommends testing before resuming sports:
    • Normal exercise tolerance Tolerance Pharmacokinetics and Pharmacodynamics test
    • 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)
    • Holter monitoring
• Serial 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) monitoring
• Re-evaluation and titration of medications, as appropriate

Differential Diagnosis

• 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: an 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 and 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 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 echocardiogram Echocardiogram Transposition of the Great Vessels showing 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.
• 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: ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage of the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy due to partial or complete obstruction 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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with acute onset chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. As in the case of 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, 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, which is usually accompanied by elevated troponins and typical ischemic 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) changes (ST elevations or depressions). Wall-motion abnormalities can be diagnosed based on a transthoracic echo. Management is with antiplatelet medications, nitrates Nitrates Nitrates are a class of medications that cause systemic vasodilation (veins > arteries) by smooth muscle relaxation. Nitrates are primarily indicated for the treatment of angina, where preferential venodilation causes pooling of blood, decreased preload, and ultimately decreased myocardial O2 demand. Nitrates, beta blockers, and revascularization Revascularization Thromboangiitis Obliterans (Buerger’s Disease).
• 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 and 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: the presence of fluid in the pericardial sac, which can cause compression Compression Blunt Chest Trauma of the heart and lead to 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 physiology. 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 physiology prevents the heart from filling and results in hemodynamic collapse. Beck’s triad Beck’s triad The triad describes the classic findings in cardiac tamponade: hypotension, jugular venous distension, muffled heart sounds on auscultation. Pericardial Effusion and Cardiac Tamponade of distended neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins: Histology, 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, and muffled heart sounds Muffled Heart Sounds Pericardial Effusion and Cardiac Tamponade is often noted on physical exam. Diagnosis is confirmed using transthoracic echocardiography Transthoracic Echocardiography Imaging of the Heart and Great Vessels, and management involves drainage of the pericardium Pericardium A conical fibroserous sac surrounding the heart and the roots of the great vessels (aorta; venae cavae; pulmonary artery). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers. Heart: Anatomy.
• 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, which is 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 of 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 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 oxygen and anticoagulation Anticoagulation Pulmonary Hypertension Drugs for most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship; thrombolytic therapies may be indicated for unstable patients Unstable Patients Blunt Chest Trauma.