What is the best treatment approach for a patient with hyper eosinophilic syndrome (HES) and endomyocardial fibrosis?

Treatment of Hypereosinophilic Syndrome with Endomyocardial Fibrosis

For patients with hypereosinophilic syndrome (HES) and endomyocardial fibrosis, immediate corticosteroid therapy (1-2 mg/kg for 1-2 weeks) is essential at treatment initiation, combined with standard heart failure management and anticoagulation, with imatinib reserved for patients with PDGFRA/PDGFRB rearrangements. 1, 2, 3

Immediate Assessment and Risk Stratification

Cardiac involvement is the most life-threatening complication and requires urgent medical assessment regardless of eosinophil count. 2 The American Heart Association emphasizes that patients with HES and occult myocardial infiltration can develop cardiogenic shock and left ventricular dysfunction upon treatment initiation due to eosinophil degranulation. 1, 3

Essential Baseline Cardiac Evaluation

• Perform echocardiogram and serum troponin testing before initiating therapy to assess for cardiac involvement, looking specifically for left/right ventricular apical obliteration, mural thrombi, or restrictive cardiomyopathy. 1, 2, 3
• Endomyocardial biopsy remains the gold standard for diagnosis of eosinophilic myocarditis, though cardiac MRI and echocardiography are helpful adjuncts. 1, 4
• If either echocardiogram or troponin is abnormal, prophylactic systemic steroids (1-2 mg/kg) for 1-2 weeks are mandatory when initiating any eosinophil-lowering therapy. 1, 3

Treatment Algorithm Based on Molecular Diagnosis

Step 1: Molecular/Genetic Testing

Accurate molecular diagnosis is essential as it dictates therapy. 2 Test for PDGFRA and PDGFRB rearrangements immediately, as their presence fundamentally changes treatment approach. 2

Step 2: Targeted Therapy Selection

For PDGFRA/PDGFRB-positive HES:

• Imatinib is the treatment of choice, with 100% complete hematologic response rates in patients with FIP1L1-PDGFRα fusion kinase. 2, 3
• Start with prophylactic corticosteroids (1-2 mg/kg) for 1-2 weeks concomitantly with imatinib to prevent cardiogenic shock from eosinophil degranulation. 1, 3
• Typical imatinib dosing ranges from 100-400 mg daily, with response durations extending beyond 30 months in published cases. 3

For PDGFRA/PDGFRB-negative or lymphocyte-variant HES:

• Corticosteroids are first-line therapy, as this represents the primary treatment for non-myeloid HES. 2, 5
• Flow cytometry and molecular analysis are required to confirm lymphocyte-variant diagnosis. 2

Critical contraindication: Patients harboring the D816V c-Kit mutation are not sensitive to imatinib and should not receive it. 3

Heart Failure Management for Endomyocardial Fibrosis

Guideline-Directed Medical Therapy

The American College of Cardiology/American Heart Association guidelines provide specific recommendations for managing the restrictive cardiomyopathy and heart failure that develops from endomyocardial fibrosis:

For patients with reduced ejection fraction (HFrEF):

• ACE inhibitors or ARBs (Class I, Level A) - reduce mortality by 26% with NNT of 17. 1
• Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) (Class I, Level A) - reduce mortality by 9% with NNT of 34. 1
• Aldosterone receptor antagonists for NYHA class II-IV with LVEF ≤35% (Class I, Level A) - reduce mortality by 6% with NNT of 30. 1
• Diuretics for volume overload (Class I, Level C). 1

For patients with preserved ejection fraction (HFpEF):

• Control systolic and diastolic blood pressure according to published guidelines (Class I, Level B). 1
• Diuretics for symptom relief from volume overload (Class I, Level C). 1

Anticoagulation Strategy

Chronic anticoagulation is indicated given the high risk of thromboembolism from mural thrombi formation along damaged myocardium. 1, 6 The thrombotic stage of eosinophilic myocarditis carries particularly high embolic risk. 1

Medications to Avoid

Calcium channel blockers (except amlodipine) are potentially harmful in HFrEF and should be avoided (Class III: Harm). 1 Most antiarrhythmic drugs, NSAIDs, and thiazolidinediones should also be withdrawn. 1

Surgical Intervention Considerations

Surgical treatment may be necessary for advanced fibrotic disease with severe valvular dysfunction or restrictive physiology refractory to medical management. 1, 7

Surgical Options

• Endocardectomy with valve replacement for severe biventricular fibrosis with mitral/tricuspid regurgitation has shown sustained improvement for over 16 months to 7 years. 7
• Bioprosthetic valve replacement is preferred over repair in acute eosinophilic endomyocarditis, as rapid disease recurrence can jeopardize conserved native valves. 8
• Cardiac transplantation may be indicated for end-stage disease refractory to all other therapies. 4

Monitoring Strategy

For persistent eosinophilia ≥1.5 × 10⁹/L for >3 months after treating infectious causes, refer to hematology. 2 Serial cardiac imaging and eosinophil counts are necessary for ongoing monitoring. 2

The 5-year mortality for HES with cardiac involvement is estimated at 30%, with outcome depending on progression of endocardial fibrosis and associated complications. 6

Critical Pitfalls to Avoid

• Delaying treatment in patients with end-organ damage leads to irreversible heart failure and mortality. 2
• Failing to test for PDGFRA rearrangements misses highly effective imatinib therapy opportunities. 2
• Starting eosinophil-lowering therapy without prophylactic steroids in patients with cardiac involvement risks cardiogenic shock. 1, 3
• Attempting mitral valve repair instead of replacement in acute disease risks rapid recurrence requiring reoperation. 8