Eosinophilic cardiomyopathy

# Overview
Eosinophillic Cardiomyopathy also known as Loeffler's Syndrome is a type of restrictive cardiomyopathy caused by eosinophillic infiltration of the endomyocardium. It is a feature of hypereosinophilic syndrome and occurs in 40-50% of all cases.  Eosinophills enter the tissue and undergo degranulation; release cytotoxic proteins; increase production of reactive oxygen species, enzymes, growth factor, and cytokines. This process leads to tissue damage and dysfunction, eventually leading to fibrosis and restrictive cardiomyopathy. There are 3 stages of the eosinophilic cardiomyopathy: Stage 1 that is acute necrotic stage, stage 2 that is mural thrombus formation, and stage 3 that is ibrotic stage. There are many causes of hypereosinophilic syndrome (HES) with eosinophilic cardiomyopathy, these can be classified as reactive, conal myeloid disorder, and idiopathic hypereosinophillic syndrome.

# Historical Perspective
- Eosinophillic Cardiomypoathy was first discovered by Wilhem Loeffler, a Swiss Physician, in 1936. 

# Classification
- Eosinophilic Cardiomyopathy may be classified according to cause into three subtypes/groups:
- Reactive 
- Clonal myeloid disorder
- Idiopathic hypereosinophillic syndrome 

# Pathophysiology
- The pathogenesis of eosinophilic cadiomyopathy is characterized by hypereosinophilia , thrombi formation , restrictive cardiomyopathy , and heart failure .
- The FLP1L1-PDGFRA fusion gene has been associated with the development chronic eosinophilic leukemia and hypereosiniophilic syndrome. 
- The PDGFRa, PDGFRb, and PDGFR1 genes have been associated with the development of clonal myeloid disorders leading to hypereosiniophilic syndrome. 
- On gross pathology, cardiac hypertrophy and fibrosis are characteristic findings of Eosinophilic Cardiomyopathy.
- On microscopic histopathological analysis, hypereosinophilia, myocardial and myofibrillar disarray, and endoperimysial interstitial fibrosis are characteristic findings of Eosinophilic Cardiomyopathy.

# Clinical Features
- Dyspnea
- Chest pain
- Cough
- Embolic events
- Fever 

# Differentiating  from other Diseases
- Eosinophilic cardiomyopathy must be differentiated from other diseases that cause cardiac hypertrophy, cardiac fibrosis, and heart failure, such as:
- Amyloidosis
- Sarcoidosis
- Hemachromatosis

# Epidemiology and Demographics
- The prevalence of hypereosinophilic syndrome is approximately 0.036 per 100,000 individuals worldwide. 

## Age
- Patients of all age groups may develop ecosinophilic cardiomyopathy.
- Eosinopilic cardiomyopathy is more commonly observed among patients aged 20-50 years old.

## Gender
- Men are more commonly affected with eosinophilic cadiomyopathy than Females.
- The male to female ratio is approximately 1.47. 

## Race
- There is no racial predilection for eosinophilic cardiomyopathy.

# Risk Factors
- Common risk factors in the development of eosinophilic cardiomyopathy are HLA Bw44 positivity, splenomegaly, thrombocytopenia, elevated vitamin B12 levels, dysplastic eosinophils, and abnormal early myeloid precursors.

# Natural History, Complications and Prognosis
- Some patients with eosinophilic cardiomyopathy may present asymptomatic.
- Early clinical features include dyspnea, fever, and chest pain.
- If left untreated, patients with eosinophilic cardiomyopathy may progress to develop heart failure, arrythmias, and sudden cardiac death.
- Prognosis is generally good, and depends on its etiology.

# Diagnosis

## Diagnostic Criteria
- The diagnosis of hypereosinophilic syndrome is made when at least one of the following three diagnostic criteria are met: 
- An elevated eosinophil count (>1500/mm3) on 2 separate tests (1 mo).
- Tissue hypereosinophilia based on >20% eosinophils in a bone marrow section.
- Marked disposition of eosinophilic granule proteins in tissue plus organ damage directly due to hypereosinophilia.

## Symptoms
- Eosinophilic cardiomyopathy is may present asymptomatic early in the course.
- Symptoms of eosinophilc cardiomypoathy may include the following: 
Fever
Dyspnea at rest or on exertion
Chest pain
Cough
Rash
Malaise
- Fever
- Dyspnea at rest or on exertion
- Chest pain
- Cough
- Rash
- Malaise

## Physical Examination
- Patients with eosinophilic cardiomyopathy usually appear distressed.
- Physical examination may be remarkable for:
Fever
Tachycardia
Tachypnea
Arrythmia
Rash
Embolic events
- Fever
- Tachycardia
- Tachypnea
- Arrythmia
- Rash
- Embolic events

## Laboratory Findings
- A positive cardiac biopsy is diagnostic of eosinophilic cardiomyopathy.
- An elevated concentration of eosinophils in peripheral blood smear is diagnostic of hypereosinophilic syndrome.
- Other laboratory findings consistent with the diagnosis of eosinophilic cardiomyopathy include:
Abnormal bone marrow biopsy
Abnormal troponins
- Abnormal bone marrow biopsy
- Abnormal troponins

## Imaging Findings
- Cardiac MRI is the imaging diagnostic study of choice for eosinophilic cardiomyopathy.
- On cardiac MRI, eosinophilic cardiomyopathy is characterized by hyper-enhancement and thrombus formation.
- Echocardiography may demonstrate:
Endomyocardial thickening
Ventricular thrombus formation
Mitral valve involvement
- Endomyocardial thickening
- Ventricular thrombus formation
- Mitral valve involvement

## Other Diagnostic Studies
- Eosinophilic cardiomyopathy may also be diagnosed using ECG.
- Findings on ECG include:
T wave inversion
Left atrial enlargement
Left ventricular hypertrophy
Right bundle branch block
- T wave inversion
- Left atrial enlargement
- Left ventricular hypertrophy
- Right bundle branch block

# Treatment

## Medical Therapy
- The treatment of eosinophilic cardiomyopathy depends on the underlying cause.
- The mainstay of therapy is supportive care.
- The mainstay of therapy for eosinophilic cardiomyopathy with a FIP1L1-PDGFRA mutation is imatinib and steroids.
- Symptomatic management includes: 
Diuretics
Beta Blockers
ACE inhibitors
Angiotensin Receptor Blockers
Digoxin
- Diuretics
- Beta Blockers
- ACE inhibitors
- Angiotensin Receptor Blockers
- Digoxin
- Imatinib acts by inhibition of tyrosine kinase.
- Response to treatment can be monitored with Echocardiography.

## Surgery
- Valve replacement may be performed for patients with valvular damage in eosinophilic cardiomyopathy.
- Cardiac transplant may be performed for patients with irreversible damage in eosinophilic cardiomyopathy.

## Prevention
- There are no primary preventive measures available for eosinophilic cardiomyopathy.
- Once diagnosed and successfully treated, patients with eosinophilic cardiomyopathy are followed-up. Follow-up testing includes Echocardiography and Electrocardiogram.