What cardiac complications should be anticipated in a patient with hyper‑eosinophilia?

Cardiac Complications in Hypereosinophilia

In hypereosinophilia, anticipate a three-stage progression of cardiac disease: acute eosinophilic myocarditis with myocardial necrosis (often subclinical but can present as fulminant heart failure), followed by intracardiac thrombus formation with high thromboembolism risk, culminating in endomyocardial fibrosis causing restrictive cardiomyopathy—with cardiac involvement being the leading cause of morbidity and mortality despite occurring in only 20% of cases. 1

Disease Progression and Pathophysiology

Hypereosinophilic syndrome causes cardiac damage through eosinophil infiltration and release of inflammatory cytokines, progressing through three distinct stages 1:

Stage 1: Necrotic Phase (Acute)

• Myocardial necrosis from direct eosinophil infiltration, often subclinical but can present as fulminant myocarditis with cardiogenic shock 1
• May present with biventricular heart failure requiring intravenous inotropes or mechanical circulatory support 1
• Sudden death from arrhythmias can occur even at this early stage 1
• Elevated serum troponin is the best early biomarker for detecting subendocardial eosinophilic infiltrates 2

Stage 2: Thrombotic Phase

• Mural thrombus formation along damaged endocardium, particularly in ventricular apices 1, 3
• High risk of systemic thromboembolism including stroke and peripheral embolization 1, 4
• Left and/or right ventricular apical obliteration may be visible on imaging 3

Stage 3: Fibrotic Phase (Chronic)

• Endomyocardial fibrosis with unfavorable myocardial remodeling 1
• Restrictive cardiomyopathy as the predominant manifestation 1, 3
• Valve damage (particularly mitral and tricuspid regurgitation) from fibrotic involvement 2, 3
• Progressive heart failure with preserved or reduced ejection fraction 3

Clinical Presentations to Anticipate

Acute presentations (5% of cases but highest mortality) 1:

• Fulminant myocarditis with hemodynamic compromise requiring urgent intervention 1
• Acute heart failure (can be biventricular) 1
• Ventricular arrhythmias and sudden cardiac death 1
• Acute coronary syndrome mimicry (chest pain, troponin elevation, ECG changes) 5

Subacute/chronic presentations 2, 3:

• Progressive dyspnea from restrictive physiology
• Thromboembolic events (stroke, peripheral embolism)
• Arrhythmias (atrial fibrillation, ventricular tachycardia)
• Signs of right heart failure (elevated JVP, peripheral edema, ascites)

Critical Diagnostic Approach

Immediate cardiac evaluation required when eosinophils >1500/μL 1, 6:

• Echocardiography to assess for left/right ventricular apical obliteration, mural thrombi, restrictive filling patterns, and valve dysfunction 6, 3
• Serum troponin before initiating therapy—elevation indicates active myocardial damage 6, 2
• Cardiac MRI for detecting subtle myocardial inflammation versus fibrosis, with specific sequences offering superior tissue characterization 2, 3
• Endomyocardial biopsy remains the gold standard but has limitations due to sampling error and eosinophil degranulation 1, 2, 3

Endomyocardial biopsy is reasonable (Class IIa) in heart failure with dilated cardiomyopathy of any duration when allergic reaction and eosinophilia are suspected 1

Management Priorities

Prevent Cardiogenic Shock During Treatment Initiation

Critical pitfall: Starting eosinophil-lowering therapy without prophylactic corticosteroids in patients with cardiac involvement risks cardiogenic shock from eosinophil degranulation 6

• Administer prophylactic corticosteroids (1-2 mg/kg) for 1-2 weeks concomitantly when initiating targeted therapy 6

Targeted Therapy Based on Molecular Diagnosis

• For PDGFRA/PDGFRB-positive HES: Imatinib is first-line with 100% complete hematologic response rates 6, 7
• For lymphocyte-variant HES: Corticosteroids are first-line therapy 7
• For idiopathic HES: Corticosteroids initially, followed by hydroxycarbamide, interferon-alpha, or imatinib for steroid-resistant cases 7

Heart Failure Management

For restrictive cardiomyopathy and reduced ejection fraction 6:

• ACE inhibitors or ARBs reduce mortality by 26% (NNT 17)
• Beta-blockers reduce mortality by 9% (NNT 34)
• Aldosterone receptor antagonists reduce mortality by 6% (NNT 30)
• Avoid calcium channel blockers (except amlodipine) in HFrEF—Class III: Harm 6

Anticoagulation

Chronic anticoagulation is indicated given the high thromboembolism risk from mural thrombi formation 6, 4

Key Prognostic Factors

Necrotizing eosinophilic myocarditis has the worst prognosis with most cases diagnosed at autopsy, characterized by diffuse inflammatory infiltrate with extensive myocyte necrosis 1

Cardiac involvement is the number one cause of morbidity and mortality in hypereosinophilic syndrome despite occurring in only 20% of cases, due to its dramatic presentation and rapidly progressive course 1

Serial cardiac imaging is necessary if cardiac involvement was present, along with follow-up eosinophil counts for ongoing monitoring 7, 2