Is there a connection between cardiac function and Behcet's disease?

Cardiac Involvement in Behçet's Disease

Yes, there is a well-established connection between cardiac function and Behçet's disease, with approximately one-third of patients developing vascular involvement that can affect the heart through multiple mechanisms including vasculitis, thrombosis, and structural cardiac abnormalities. 1

Mechanisms of Cardiac Involvement

Behçet's disease is a small vessel vasculitis that uniquely affects both arteries and veins of all sizes, making it one of only two vasculitides with venous involvement. 1 The pathophysiology involves:

• Vasculitic inflammation with lymphocytic infiltration mixed with histiocytes and eosinophils, particularly affecting the vasa vasorum of the media and adventitia 1
• Destruction of the arterial media leading to aneurysm formation, pseudoaneurysm development, and potential rupture 1
• Granuloma formation in the adventitial layer with augmented cytokine and matrix metalloproteinase production causing vessel destruction 1

Specific Cardiac Manifestations

Structural and Functional Abnormalities

Patients with Behçet's disease demonstrate significant diastolic dysfunction compared to controls, with measurable echocardiographic abnormalities even in the absence of symptoms. 2 A meta-analysis of 1,624 subjects revealed:

• Prolonged mitral deceleration time (14.20 ms longer, p < 0.0001) 2
• Increased isovolumetric relaxation time (7.29 ms longer, p < 0.00001) 2
• Lower E/A ratio (-0.24, p = 0.05) indicating impaired ventricular relaxation 2
• Reduced ejection fraction (-1.08%, p < 0.0001) 2
• Enlarged left atrial dimension (0.08 cm larger, p = 0.0008) 2
• Increased aortic diameter (0.16 cm larger, p = 0.02) 2

Clinical Cardiac Lesions

The spectrum of cardiac involvement includes: 3, 4, 5

• Pericarditis - inflammatory involvement of the pericardium
• Myocarditis - direct myocardial inflammation leading to systolic and diastolic dysfunction
• Intracardiac thrombosis - predominantly right-sided thrombi
• Endomyocardial fibrosis - chronic sequela of inflammation
• Valvular dysfunction - endocarditis and valvular involvement
• Coronary artery disease - including vasculitis, thrombosis, aneurysms, and rupture
• Myocardial aneurysms - rare but serious complication

Silent Myocardial Ischemia

Silent myocardial ischemia occurs in 25% of Behçet's patients, significantly higher than controls (p < 0.001), and is strongly associated with major vascular involvement. 6 Key findings include:

• ST segment depression averaging 3.00 ± 0.42 mm with duration of 4.01 ± 0.9 minutes 6
• 78% of patients with silent ischemia had major vascular involvement elsewhere (p = 0.0022) 6
• Coronary angiography is typically normal, suggesting microvascular disease rather than epicardial coronary stenosis 6
• Impaired endothelial cell function is the likely underlying mechanism 6

Vascular Complications Affecting Cardiac Function

Aortic Involvement

• Aneurysm formation can occur at multiple sites and progress unpredictably to rupture, which can be fatal 1
• Anastomotic pseudoaneurysms occur in 12.9% of patients within 18 months after surgical repair due to ongoing inflammation at suture lines 1
• The ascending aorta and aortic root can be affected, though less commonly than in other vasculitides 1

Venous Thrombosis

• Deep vein thrombosis and superficial thrombophlebitis are common manifestations 1
• Post-thrombotic syndrome frequently develops with recurrent thrombosis, potentially causing difficult-to-treat complications 7, 8

Clinical Implications and Risk Stratification

Young men with early disease onset face the highest risk of severe cardiac and vascular complications, requiring aggressive early immunosuppression. 7, 8, 9

High-Risk Features for Cardiac Involvement:

• Male gender with early disease onset 7, 9
• Presence of major vascular involvement elsewhere 6
• Active systemic inflammation 7

Treatment Approach for Cardiac Involvement

Acute Cardiac Manifestations

For acute cardiac involvement, treatment follows the same immunosuppressive principles as other major organ involvement:

• High-dose glucocorticoids: Start with 1 mg/kg/day prednisolone or IV methylprednisolone 1 g/day for 3-7 days 7
• Azathioprine: 2.5 mg/kg/day as steroid-sparing agent 7
• Cyclophosphamide: For arterial aneurysms and severe vascular complications 7

Critical Treatment Considerations

Anticoagulants should generally be avoided in Behçet's disease with venous thrombosis due to bleeding risk, especially with coexisting pulmonary arterial aneurysms. 7, 8 Instead:

• Use immunosuppressive agents (corticosteroids, azathioprine, cyclophosphamide, or cyclosporine A) for acute deep vein thrombosis 7
• Avoid cyclosporine A in patients with any central nervous system involvement due to neurotoxicity risk 7, 8

Refractory Disease

For severe or refractory cardiac involvement:

• TNF-α inhibitors (infliximab) show promise, particularly when combined with azathioprine 7, 5
• Screen for tuberculosis before initiating anti-TNF therapy, as endemic areas for Behçet's overlap with TB-endemic regions 7

Monitoring Recommendations

Given the high prevalence of subclinical cardiac involvement:

• Baseline echocardiography should be considered in all Behçet's patients to assess for diastolic dysfunction and structural abnormalities 2
• Ambulatory cardiac monitoring may detect silent myocardial ischemia, particularly in patients with major vascular involvement 6
• Advanced imaging techniques (cardiac MRI, nuclear studies) can reveal subclinical myocardial dysfunction and fibrosis 5
• Regular assessment even during remission periods, especially in those with history of major organ involvement 9

Common Pitfalls

• Assuming normal coronary angiography excludes cardiac ischemia - microvascular disease is the primary mechanism in Behçet's, not epicardial stenosis 6
• Treating venous thrombosis with anticoagulation alone - immunosuppression is the primary treatment, not anticoagulation 7, 8
• Underestimating surgical risk - anastomotic pseudoaneurysms are common due to ongoing inflammation at suture sites 1
• Missing subclinical cardiac involvement - diastolic dysfunction and silent ischemia are prevalent even without symptoms 6, 2