Endomyocardial (eosinophilic) disease - Clinicals, Diagnosis, and Management

Cardiovascular

Clinicals - History

Fact Explanation
Is an idiopathic disease Hyper eosinophilc syndrome (HES) is a poorly understood syndrome characterized
by the presence of persistent hypereosinophilia (>1,500
eosinophils 106
/L of peripheral blood for >6 months) and
signs or symptoms of multisystemic organ dysfunction in
the absence of other known causes of eosinophilia. Cardiac involvement in this is present in 50%- 60% and is termed as Loeffler's endocarditis or eosinophilic endomyocardial disease. The biopsy specimens show the presence of degranulated eosinophils or eosinophilc cationic proteins in the endocardium and activated eosinophils in the myocardium. Endocardium gets thickened as well as affecting the myocardium. In this eosinophils may be associated with myocardial inflammation in three distinct forms. The first is a hypersensitivity reaction to a foreign antigen known as allergic esosinophilic myocarditis and is often drug induced. Then a thrombotic stage resulting in splenic, renal, retinal, cerebral thrombosis. Finally it may present in the form of fulminant necrotic myocarditis of unclear etiology.
Is an idiopathic disease
Hyper eosinophilc syndrome (HES) is a poorly understood syndrome characterized
by the presence of persistent hypereosinophilia (>1,500
eosinophils 106
/L of peripheral blood for >6 months) and
signs or symptoms of multisystemic organ dysfunction in
the absence of other known causes of eosinophilia. Cardiac involvement in this is present in 50%- 60% and is termed as Loeffler's endocarditis or eosinophilic endomyocardial disease. The biopsy specimens show the presence of degranulated eosinophils or eosinophilc cationic proteins in the endocardium and activated eosinophils in the myocardium. Endocardium gets thickened as well as affecting the myocardium. In this eosinophils may be associated with myocardial inflammation in three distinct forms. The first is a hypersensitivity reaction to a foreign antigen known as allergic esosinophilic myocarditis and is often drug induced. Then a thrombotic stage resulting in splenic, renal, retinal, cerebral thrombosis. Finally it may present in the form of fulminant necrotic myocarditis of unclear etiology.
Exertional chest pain In the early stage of the illness due to necrosis of cardiac myocytes, there could be carditis, resulting in chest pain. Exertional chest pain
In the early stage of the illness due to necrosis of cardiac myocytes, there could be carditis, resulting in chest pain.
Ankle swelling In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in bi ventricular failure, a diastolic failure to be exact, hence ankle swelling. Ankle swelling
In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in bi ventricular failure, a diastolic failure to be exact, hence ankle swelling.
Shortness of breath In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in bi ventricular failure,a diastolic failure to be exact, and left ventricular failure results in pulmonary congestion hence this Shortness of breath
In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in bi ventricular failure,a diastolic failure to be exact, and left ventricular failure results in pulmonary congestion hence this
Orthopnoea/ Paroxymal nocturnal dyspnoea In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in biventricular failure, and left ventricular failure results in pulmonary congestion hence this Orthopnoea/ Paroxymal nocturnal dyspnoea
In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in biventricular failure, and left ventricular failure results in pulmonary congestion hence this
weight loss This is a symptom of acute carditis, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this weight loss
This is a symptom of acute carditis, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Fever This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Fever
This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Cough This is a symptom of acute carditis, associated with this Cough
This is a symptom of acute carditis, associated with this
pruritic skin rash This is a symptom of hyper eosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this pruritic skin rash
This is a symptom of hyper eosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Excessive sweating This is a symptom of hyper eosinophilia resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Excessive sweating
This is a symptom of hyper eosinophilia resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Palpitations Due to myocarditis, there could be abnormal rhythm generation from the heart causing ventricular arrhythmias. Palpitations
Due to myocarditis, there could be abnormal rhythm generation from the heart causing ventricular arrhythmias.
Hemiparesis/ Aphasia (Transient ischemia like manifestaions) In this, eosinophil granule proteins, especially MBP1 and the eosinophil peroxidase, can activate platelets and impair the anticoagulant effects of thrombomodulin and cause thrombosis and embolism to the brain and transient ischemic syndrome like manifestations Hemiparesis/ Aphasia (Transient ischemia like manifestaions)
In this, eosinophil granule proteins, especially MBP1 and the eosinophil peroxidase, can activate platelets and impair the anticoagulant effects of thrombomodulin and cause thrombosis and embolism to the brain and transient ischemic syndrome like manifestations
Sudden death Due to ventricular arrhythmias ultimately causing ventricular fibrillation and due to cerebrovascular accidents both can result in sudden death Sudden death
Due to ventricular arrhythmias ultimately causing ventricular fibrillation and due to cerebrovascular accidents both can result in sudden death

Clinicals - Examination

Fact Explanation
Cachexia This is a symptom of hyper eosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Cachexia
This is a symptom of hyper eosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Fever This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Fever
This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Skin rash This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Skin rash
This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Increased jugular venous pressure In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in bi ventricular failure, a diastolic failure to be exact, hence venous congestion and this. Increased jugular venous pressure
In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in bi ventricular failure, a diastolic failure to be exact, hence venous congestion and this.
Dependent oedema In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in biventricular failure, a diastolic failure to be exact, hence this. Dependent oedema
In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in biventricular failure, a diastolic failure to be exact, hence this.
Hepatomegaly In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in biventricular failure, a diastolic failure to be exact, hence venous congestion and this. Hepatomegaly
In later stages due to fibrosis of the endocardium and myocardium, there's restrictive cardiomyopathy resulting in biventricular failure, a diastolic failure to be exact, hence venous congestion and this.
Splenomegaly This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Splenomegaly
This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Holo systolic murmur in the apical area Due to myocarditis causing damage to the mitral valve leaflet and mitral regurgitation Holo systolic murmur in the apical area
Due to myocarditis causing damage to the mitral valve leaflet and mitral regurgitation
Irregular pulse Due to myocarditis, there could be abnormal rhythm generation from the heart causing ventricular arrhythmias. Irregular pulse
Due to myocarditis, there could be abnormal rhythm generation from the heart causing ventricular arrhythmias.
Retinal lesions This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this Retinal lesions
This is a symptom of hypereosinophilia, resulting in release of cytokines from eosinophils and causing constitutional symptoms associated with this
Hypotension, cold clammy peripheries This is due to acute myocarditis presenting with cardiogenic shock resulting in inadequate cardiac output, hence hypertension and reduced perfusion hence cold clammy peripheries Hypotension, cold clammy peripheries
This is due to acute myocarditis presenting with cardiogenic shock resulting in inadequate cardiac output, hence hypertension and reduced perfusion hence cold clammy peripheries

Investigations - Diagnosis

Fact Explanation
Full blood count Performed to look for the presence of eosinophils. Note that Peripheral eosinophilia isn't mandatory for the diagnosis of Loeffler endocarditis. Full blood count
Performed to look for the presence of eosinophils. Note that Peripheral eosinophilia isn't mandatory for the diagnosis of Loeffler endocarditis.
Cytogenetics, fluorescent in situ hybridization (FISH), and molecular analysis This can show the presence of the FIP1L1-PDGFRA fusion gene Cytogenetics, fluorescent in situ hybridization (FISH), and molecular analysis
This can show the presence of the FIP1L1-PDGFRA fusion gene
Electrocardiogram This will show nonspecific ST-segment and T-wave abnormalities and arrhythmias including atrial fibrillation and ventricular arrhythmias. Electrocardiogram
This will show nonspecific ST-segment and T-wave abnormalities and arrhythmias including atrial fibrillation and ventricular arrhythmias.
Echocardiography Shows a restrictive pattern filling with left ventricular systolic function preserved and valvular regurgitaion and apical thrombus in the left ventricle also has been reported Echocardiography
Shows a restrictive pattern filling with left ventricular systolic function preserved and valvular regurgitaion and apical thrombus in the left ventricle also has been reported
Doppler studies using echocardiogram This will show restrictive cardiomyopathy Doppler studies using echocardiogram
This will show restrictive cardiomyopathy
cardiac catheterization May show severely elevated pressure in ventricular filling and the presence of tricuspid or mitral regurgitation. cardiac catheterization
May show severely elevated pressure in ventricular filling and the presence of tricuspid or mitral regurgitation.
endomyocardial biopsy This remains the investigation of choice and histologic specimens show thick and deep layers of loosely arranged collagen tissue localized to the endocardium primarily, they may have strands extending into the myocardium underlying as well and eosinophilic infiltration which is not commonly seen. Also it may show extensive interstitial edema associated with necrosis of myocytes, diffuse infiltration of inflammatory cells with lymphocytes, neutrophils endomyocardial biopsy
This remains the investigation of choice and histologic specimens show thick and deep layers of loosely arranged collagen tissue localized to the endocardium primarily, they may have strands extending into the myocardium underlying as well and eosinophilic infiltration which is not commonly seen. Also it may show extensive interstitial edema associated with necrosis of myocytes, diffuse infiltration of inflammatory cells with lymphocytes, neutrophils
MRI of the chest Right ventricular mild systolic and diastolic dysfunction and extensive subendocardial delayed contrast enhancement suggests endomyocardial fibrosis MRI of the chest
Right ventricular mild systolic and diastolic dysfunction and extensive subendocardial delayed contrast enhancement suggests endomyocardial fibrosis
Nuclear imaging This is done with gallium67- or indium111-labeled antimyosin antibodies can be useful in assessing myocardial dysfunction but there are no specific features that help establish the diagnosis Nuclear imaging
This is done with gallium67- or indium111-labeled antimyosin antibodies can be useful in assessing myocardial dysfunction but there are no specific features that help establish the diagnosis

Investigations - Management

Fact Explanation
full blood count In patient serial full blood counts are done to assess peripheral eosinophilia. full blood count
In patient serial full blood counts are done to assess peripheral eosinophilia.
Echocardiography Serial echocardiographic investigations are done to evaluate ejection fraction, diastolic dysfunction and response to treatment. Echocardiography
Serial echocardiographic investigations are done to evaluate ejection fraction, diastolic dysfunction and response to treatment.
Serum electrolytes Since patients are put on diuretics for congestive cardiac failure and angiotensinogen converting enzyme inhibitors it's important to monitor serum electrolytes Serum electrolytes
Since patients are put on diuretics for congestive cardiac failure and angiotensinogen converting enzyme inhibitors it's important to monitor serum electrolytes
Liver function tests As patients are put on immunosuppressants, it's important to monitor liver function tests to detect drug induced side effects Liver function tests
As patients are put on immunosuppressants, it's important to monitor liver function tests to detect drug induced side effects
Prothrombin time and international normalization ratio As patients are put on Warfarin to combat thrombo-embolism, it's important to monitor this Prothrombin time and international normalization ratio
As patients are put on Warfarin to combat thrombo-embolism, it's important to monitor this
Full blood count This is done to exclude significant anaemia and any quantitative platelet or leukocyte abnormality Full blood count
This is done to exclude significant anaemia and any quantitative platelet or leukocyte abnormality
Serum Creatinine and Blood urea nitogen, and serum electrolyes As these patients are on chronic diuretic therapy it may produce total-body sodium and potassium depletion, and uraemia. Hypokalaemia is a relatively common finding in cardiac surgical patients. Also to assess renal function Serum Creatinine and Blood urea nitogen, and serum electrolyes
As these patients are on chronic diuretic therapy it may produce total-body sodium and potassium depletion, and uraemia. Hypokalaemia is a relatively common finding in cardiac surgical patients. Also to assess renal function
Coagulation profile To exclude any coagulopathy, and also specially since patients are on Warfarin this is important Coagulation profile
To exclude any coagulopathy, and also specially since patients are on Warfarin this is important
Echocardiography To evaluate the ejection fraction, and valvular regurgitation prior to cardiac surgery Echocardiography
To evaluate the ejection fraction, and valvular regurgitation prior to cardiac surgery
Cardio-pulmonary exercise testing To evaluate the cardiac function before cardiac surgery Cardio-pulmonary exercise testing
To evaluate the cardiac function before cardiac surgery
Cytogenetics, fluorescent in situ hybridization (FISH), and molecular analysis This can show the presence of the FIP1L1-PDGFRA fusion gene Cytogenetics, fluorescent in situ hybridization (FISH), and molecular analysis
This can show the presence of the FIP1L1-PDGFRA fusion gene

Management - Supportive

Fact Explanation
Patient education Patient should be educated on the aetiology of the disease, the course, importance of follow up, the advices regarding Warfarin and other medication, diet and exercise Patient education
Patient should be educated on the aetiology of the disease, the course, importance of follow up, the advices regarding Warfarin and other medication, diet and exercise
Management of heart failure with pharmacological therapy Patients are put on heart failure regime once the heart failure ensues. Diuretics, Digoxin, After-load reduction with angiotensinogen converting enzyme inhibitors are used Management of heart failure with pharmacological therapy
Patients are put on heart failure regime once the heart failure ensues. Diuretics, Digoxin, After-load reduction with angiotensinogen converting enzyme inhibitors are used
Anticoagulant therapy Anticoagulant therapy is started with Warfarin to combat thrombo-embolism related to cardiac dysfunction. Anticoagulant therapy
Anticoagulant therapy is started with Warfarin to combat thrombo-embolism related to cardiac dysfunction.
Diet Special restrictions in the diet is unnecessary except for low salt diet in congestive cardiac failure Diet
Special restrictions in the diet is unnecessary except for low salt diet in congestive cardiac failure
Exercise Strenuous exercises are avoided and moderate endurance aerobic activities are advised. Exercise
Strenuous exercises are avoided and moderate endurance aerobic activities are advised.

Management - Specific

Fact Explanation
Pharamacological therapy with Corticosteroids Corticosteroids is used in acute myocarditis, and may prolong survival as well. Pharamacological therapy with Corticosteroids
Corticosteroids is used in acute myocarditis, and may prolong survival as well.
Pharamacological therapy with cytotoxic drugs, including hydroxyurea Early phases of the disease can be treated with immune suppressant and cytotoxic medications, and thought to increase survival as well Pharamacological therapy with cytotoxic drugs, including hydroxyurea
Early phases of the disease can be treated with immune suppressant and cytotoxic medications, and thought to increase survival as well
Pharamacological therapy with tyrosine-kinase inhibitors Treatment with low-dose imatinib, which is Tyrosine-Kinase inhibitor cause rapid regression of both eosinophilic proliferation and endomyocardiopathy Pharamacological therapy with tyrosine-kinase inhibitors
Treatment with low-dose imatinib, which is Tyrosine-Kinase inhibitor cause rapid regression of both eosinophilic proliferation and endomyocardiopathy
Pharamacological therapy with interferons Interferon alpha appears to be of some success in reducing eosinophilic degranulation Pharamacological therapy with interferons
Interferon alpha appears to be of some success in reducing eosinophilic degranulation
Surgical treatment with endocardiectomy Directed toward the predominant location of the restrictive process and is done when restrictive process is so advanced, especially in patients with congestive heart failure refractory to medical therapy Surgical treatment with endocardiectomy
Directed toward the predominant location of the restrictive process and is done when restrictive process is so advanced, especially in patients with congestive heart failure refractory to medical therapy
Surgical treatment with valve replacement or repair The mitral and tricuspid valves which are damaged during the disease process can be replaced or repair Surgical treatment with valve replacement or repair
The mitral and tricuspid valves which are damaged during the disease process can be replaced or repair
Heart transplant When other surgical procedures limit the success, heart transplantation remains the last choice Heart transplant
When other surgical procedures limit the success, heart transplantation remains the last choice

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