Myocarditis & IE

Clinical Pharmacy Department

Introduction
Myocarditis is classified as a rare disease but is
estimated to affect thousands of adults and
children in the U.S. and around the world each
year. 3.1 million cases of myocarditis and
cardiomyopathy were diagnosed in 2017
(statistics posted in Lancet, November 2018).
Myocarditis is a serious yet rare condition where
inflammation develops in the myocardium, the
middle muscular layer of the heart wall. It
involves an inflammatory infiltrate of the
myocardium with lymphocytes, neutrophils,
eosinophils, giant cells, granulomas, or a mixture.
 Introduction

Myocardial inflammation can be diffuse or focal.

Inflammation can extend into the pericardium causing myopericarditis. The extent of
myocardial involvement and extension into adjacent pericardium can determine the type of
symptoms.
Diffuse involvement can lead to heart failure, arrhythmias and sometimes sudden cardiac
death.
Focal involvement is less likely to cause heart failure but can lead to arrhythmias and
sudden cardiac death. Involvement of the pericardium leads to chest pain and other
symptoms typical of pericarditis. Some patients remain asymptomatic whether myocardial
involvement is focal or diffuse.
Causes
The condition may be acute and resolve quickly , or it may be subacute or chronic, lasting
up to three months. In severe cases, myocarditis may lead to heart failure or death.
Common causes are Infective or non-infective or idiopathic
Infective
1- Viral infection (such as the flu, Covid-19)
2- Bacterial infection (such as staph or strep)
3- Fungal infection (such as candidiasis)
Non-infective
4- Medications (antibiotics such as penicillin, psychiatric medicines such as clozapine, and
diuretics such as furosemide and hydrochlorothiazide), autoimmune disorders and toxic
substances can also cause it.
 Giant cell myocarditis
Giant cell myocarditis is a rare form of
myocarditis with a fulminant course. The etiology
is unclear but may include an autoimmune
mechanism. Biopsy shows characteristic
multinucleated giant cells. Patients with giant cell
myocarditis present in cardiogenic shock and
frequently have intractable ventricular
arrhythmias or complete heart block. Giant cell
myocarditis has a poor prognosis but is important
to rule out in the setting of an otherwise healthy
patient presenting in fulminant heart failure or
with intractable arrhythmias because
immunosuppressive therapy can help improve
survival.
 People with myocarditis don’t always have
symptoms. Others have mild or severe signs, such as:
1-Fatigue or exercise intolerance
2-Shortness of breath
3-Fever
4-Chest pain
5-Hard, rapid or irregular heartbeat
Symptoms 6-Lightheadedness or fainting
7-Flu-like symptoms including headache, body ache,
joint pain or sore throat.
It may lead to heart failure ( mitral regurgitation and
tricuspid regurgitation may be present in patients with
ventricular enlargement., Arrythmia or rarely
cardiogenic shock (a condition that occurs when the
heart suddenly cannot pump enough blood to the
tissues and organs).
Diagnosis

Cardiac enzymes can be

abnormal in patients with acute
myocarditis. Cardiac troponin
Blood tests (CBC) and CK-MB (creatine kinase Cardiac MRI (CMR) Chest X-ray
muscle band isoenzyme) can
both be elevated due to necrosis
of cardiac myocytes.

Cardiac
Echocardiography,
EKG/ECG catheterization with
also called
(electrocardiogram) coronary angiography
ultrasound
and biopsy
Diagnosis of causes
After myocarditis is diagnosed, tests to determine etiology are done. In a young, previously healthy adult who presents with
symptoms of a viral infection and myocarditis, an extensive evaluation is usually unnecessary. Differentiating viral from
idiopathic myocarditis is difficult, expensive, and generally of little practical importance.

A complete blood count (CBC) is helpful to assess for peripheral eosinophilia, which is present in hypersensitivity
myocarditis.

Cardiac catheterization may be useful for ruling out ischemia since myocarditis can mimic myocardial infarction or
myocardial ischemia.

In other cases, a biopsy of myocardial tissue may be needed to establish a diagnosis. Acid-fast stains of myocardial tissue
are essential if tuberculosis (TB) is considered possible (TB myocarditis can be aggressive and can worsen rapidly with
corticosteroid therapy). Myocardial samples are examined for giant cells, which are characteristic of giant cell myocarditis,
and the granulomas that occur in sarcoidosis.

Other tests include acute-phase reactants, routine chemistry tests, cultures, autoimmune tests, and, when appropriate,
tests for HIV infection, SARS-CoV-2 infection,, and antibody tests for coxsackievirus, influenza virus, and streptococcus.
 Treatment

Treatment of heart failure includes diuretics and nitrates for symptomatic relief.
In cases of fulminant heart failure, intra-aortic balloon pump (IABP), left ventricular assist
device (LVAD), or transplantation may be necessary.
Long-term pharmacotherapy of heart failure involves angiotensin-converting enzyme (ACE)
inhibitors, beta-blockers, aldosterone antagonists, angiotensin II receptor blockers (ARBs), or
angiotensin receptor/neprilysin inhibitors (ARNIs).
Atrial and ventricular arrhythmias are treated with antiarrhythmic therapy. Heart block can be
treated with temporary pacing but may require insertion of a permanent pacemaker if
conduction abnormalities persist.
 Infectious myocarditis is generally treated with supportive therapy for associated heart
failure and arrhythmias. Antiviral therapy has not been shown to be helpful in the
treatment of most viral etiologies, but nirmatrelvir and ritonavir can help treat
myocarditis due to SARS-CoV2 infection , and oseltamivir can help treat myocarditis
due to influenza.
Corticosteroids may also help treat myocarditis due to SARS-CoV2 infection. Bacterial
etiologies may be treated with antibiotics, but antibiotics have not been shown to be
Treatment effective except possibly in the acute infectious phase. Parasitic infection should be
treated with appropriate antiparasitic medications.
Corticosteroids are appropriate for patients with eosinophilic or giant cell myocardial
infiltrations or myocarditis due to systemic rheumatic disorders. Hypersensitivity
myocarditis is treated by immediate discontinuation of the causative medication or
cardiotoxin and corticosteroid therapy.
Patients with giant cell myocarditis have improved survival when treated with
immunosuppressants, usually corticosteroids and cyclosporine. Myocarditis caused by
sarcoidosis can be treated with corticosteroids or other immunosuppressants
Infective endocarditis (IE)

It also known as bacterial endocarditis, involves inflammation of the endocardium (the

lining of the heart) and valves that is caused by bacteremia. Bacteremia allows for
colonization of a vegetation that is formed when damaged endocardium results in platelet
aggregation and activation of the coagulation cascade.
Approximately 80% to 90% of IE cases are due to gram-positive streptococci,
staphylococci, and enterococci, with Staphylococcus aureus responsible for about 30% of
cases. Other organisms, including Haemophilus, Aggregatibacter, Cardiobacterium,
Eikenella, and Kingella (HACEK), are less frequently the cause of infection. Although
fungal endocarditis due to Candida and Aspergillus is rare, it can be fatal
Clinical presentation

IE can present as an acute or subacute infection.

Acute infections present and progress rapidly. They are characterized by high fevers,
rigors, and sepsis in healthy hearts.
Subacute endocarditis is delayed and presents with nonspecific symptoms, including
weight loss, fatigue, and dyspnea over weeks to months, often in patients with
preexisting heart disease. Subacute cases are usually due to penicillin-sensitive viridans
group Streptococcus (VGS), while S aureus is responsible for acute IE. Unfortunately,
even after treatment, for patients who present with acute IE, there is an increased chance
of death due to cardiac failure within weeks to months, while those who have subacute
IE rarely have severe cardiac damage.
Diagnosis

The diagnosis of IE has been based upon microbiologic and echocardiographic evidence
recommendations from the Modified Duke Criteria, last updated in 2000.

In 2023, the International Society for Cardiovascular Infectious Diseases suggested significant
updates to the Duke Criteria due to changes in microbiology, diagnostics, epidemiology, and
treatment. Updates were suggested in three areas: pathologic criteria, major clinical criteria, and
minor clinical criteria.

Overall, clinical criteria for diagnosis remain unchanged and require 1) two major criteria, 2) one
major criterion and three minor criteria, or 3) five minor criteria
Diagnosis(Duke Criteria)
Consider infectious endocarditis if two major criteria or one major and three minor
criteria or five minor criteria.
Major criteria:
1- ≥2 blood cultures with concerning organism (viridans streptococci, HACEK,
Staphylococcus aureus, enterococci) or persistent bacteremia separated by at least 12 h
(Yield of blood cultures is directly related to volume of blood cultured, with properly filled
blood culture bottles (i.e., 10 ml of blood is essential).
2- Echocardiogram with oscillating intracardiac mass on valve or surrounding
anatomy, dehiscence (breakdown of sutures) of prosthetic valve, new valvular regurgitation,
or abscess
Diagnosis(Duke Criteria)
Minor criteria
-Predisposing heart condition (unrepaired congenital heart disease, intravenous drug use).
Fever (≥38.0 °C)
-Vascular phenomena (major arterial emboli, pulmonary infarcts, mycotic
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions)
-Immunologic phenomena (glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor)
Other concerning positive blood cultures or serology for endocarditis
Investigations
1-Initial test:
● Blood cultures:3 times, 3 different sites and 3 different needle → to identify the organism
● ECHO mostly TTE (vegetation , abnormality of the valves).
2- Further test:
● C.B.C : Shows leukocytosis + anemia
● ESR : Will be elevated
● RFT : Shows Glomerulonephritis
● URINE : Shows hematuria
● ECG: shows first degree block
● Chest X-Ray: Shows cardiomegaly, pulmonary embolism.
Treatment (Bacteria)
Empirical treatment (or culture Negative treatment)
Native Valve:
Vancomycin(15mg/Kg/6hrs)+ Ceftriaxone (50mg/kg/12hrs) or Gentamicin(7.5mg/kg/Day, preferred
to be divided every 8hrs)
Duration: 4 weeks

Prosthetic Valve:
Vancomycin(15mg/Kg/6hrs)+ (Ceftriaxone (50mg/kg/12hrs) or Gentamicin(7.5mg/kg/Day, preferred
to be divided every 8hrs) + Rifampicin(15-20 mg/kg/12hrs)

Duration: 6 weeks
 Candida
Positive blood cultures for Candida species
Etiology:
* Candida albicans
Non-albicans Species

Treatment Duration:
6 weeks or longer if patient has myocardial abscess
or delayed resolution of candida.
Long-term, possibly lifelong suppression with
Fluconazole(6-12 mg/kg, Max 400 mg/dose, for
prosthetic valve endocarditis)
*Valve replacement is strongly recommended
specially in patients with prosthetic valve.
 Caspofungin (70 mg/m2/dose on day 1 the
50mg/m2/dose , can be increased to 70mg/m2/dose if
inadequate response)

Treatment Micafungin/Anidulafungin

Candida Alternatively
Fluconazole (Diflucan) (12mg/kg/day, max 800mg)
Amphotericin B (Fungizone) (1mg/kg/dose with or
without flucytosine)
Case 1
1-The condition associated with the highest risk of developing infective endocarditis (IE) is:
A. Mitral valve prolapse with regurgitation.
B. The presence of prosthetic heart valve.
C. Rheumatic fever without valvular defects.
D. Dilated cardiomyopathy.
Case 2
Which of the following organisms is not commonly implicated in infective endocarditis?
A. Streptococcus species.
B. Staphylococcus species.
C. Enterococcus species.
D. Candida species.
Case 3
10-year-old boy presents to the emergency department with chest pain, fever, fatigue, and
arthralgias. His past medical history is significant for rheumatic heart disease and a recent
dental procedure. He currently shows no "stigmata" of endocarditis on physical
examination, although endocarditis is suspected. The most likely organism is:
A. viridans streptococci.
B. Staphylococcus aureus.
C. Enterococcus fecalis.
D. Pseudomonas.
Case 4
A patient that recently had mitral valve replacement (38 days ago) was admitted to the clinic
with persistent fever and malaise. Endocarditis is suspected, and the most likely etiology is:
A. Escherichia Coli.
B. viridans streptococci.
C. Staphylococcus epidermitis.
D. Enterococcus fecalis.
Case 5
Based on the recent IE diagnostic criteria, the two most important parameters for the
diagnosis of this infection are
A. laboratory abnormalities and positive blood cultures.
B. positive blood cultures and echocardiographic changes.
C. ECG changes and positive physical findings.
D. positive physical findings and positive blood cultures.
Case 6
15-year-old girl is scheduled for a major dental extraction in 3 days. She has a history of
prosthetic valve replacement. She is allergic to penicillin. Her physician asks whether she
should receive antibiotic prophylaxis before her procedure. The most appropriate response
is:
A. yes, ampicillin 2 g orally 1 hour before the procedure.
B. yes, clindamycin 600 mg orally 1 hour before the procedure.
C. yes, cephalexin 500 mg orally 2 hours before the procedure.
D. no, the most recent guidelines do not recommend prophylaxis in this situation.
Thank you