What evidence supports myocardial strain imaging (speckle‑tracking echocardiography) and global longitudinal strain for detecting cardiac involvement in systemic sarcoidosis?

Myocardial Strain Imaging for Cardiac Sarcoidosis Detection

Speckle-tracking echocardiography with global longitudinal strain (GLS) measurement is a highly effective early detection tool for cardiac sarcoidosis, identifying subclinical myocardial involvement before conventional echocardiography shows abnormalities, with LV GLS values > -16.3% providing 82% sensitivity and 81% specificity for diagnosis. 1

Diagnostic Performance in Early Cardiac Sarcoidosis

Detection of Subclinical Disease

• Patients with extracardiac sarcoidosis and normal LVEF (>52-54%) demonstrate significantly reduced LV GLS compared to healthy controls (-15.9% vs -18.2%, p=0.001), indicating myocardial involvement despite preserved ejection fraction. 1

• LV GLS is significantly impaired in sarcoidosis patients with normal cardiac function by standard echocardiography (-17.2% vs -21.3% in controls, p<0.0001), demonstrating superior sensitivity over conventional imaging. 2

• A meta-analysis of 967 patients confirmed that LVGLS is significantly lower in extracardiac sarcoidosis patients compared with controls (SMD -3.98,95% CI: -5.32 to -2.64, P<0.001), establishing this as a consistent finding across multiple studies. 3

Specific Diagnostic Thresholds

• LV GLS > -16.3% (less negative than -16.3%) provides optimal diagnostic accuracy with 82.2% sensitivity and 81.2% specificity (AUC 0.91) for identifying cardiac sarcoidosis. 1

• RV GLS > -19.9% demonstrates even higher diagnostic performance with 88.1% sensitivity and 86.7% specificity (AUC 0.93) for cardiac sarcoidosis detection. 1

• These thresholds are particularly valuable because they identify disease before structural abnormalities, wall motion abnormalities, or LVEF reduction become apparent. 1

Correlation with Advanced Imaging

Comparison with Cardiac MRI

• Circumferential strain via speckle-tracking identifies myocardial segments with delayed enhancement on cardiac MRI, with DE+ segments showing significantly lower peak circumferential strain than DE- segments (-14% vs -28%, P<0.0001). 4

• Longitudinal strain in DE+ segments is significantly decreased compared with control segments (-19% vs -23%, P=0.005), confirming that strain abnormalities correspond to actual myocardial damage. 4

• Radial strain does not reliably differentiate damaged from normal myocardium in sarcoidosis (41% in DE+ vs 45% in DE- vs 46% in controls, P=0.50), making it less useful than longitudinal and circumferential strain. 4

Prognostic Value

Prediction of Major Cardiac Events

• Impaired LV GLS is significantly associated with clinical outcomes including mortality, heart failure, arrhythmia, and cardiac device implantation (HR 1.56; 95% CI 1.16-2.11, p<0.01). 2

• LVGLS correlates with major cardiac events in cardiac sarcoidosis patients, with significantly lower values in those who suffered events (SMD -3.89,95% CI -6.14 to -1.64, P<0.001). 3

• Hospital admission and heart failure significantly correlate with LV GLS values > -14% (less negative than -14%), identifying a high-risk threshold for adverse outcomes. 1

Risk Stratification

• Serial monitoring of GLS can track disease progression, as reduction in GLS over time indicates pathological deterioration requiring treatment intensification. 5, 6

• The presence of reduced strain values despite normal LVEF identifies patients who require closer monitoring and consideration for advanced imaging with cardiac MRI or PET. 7

Strain Pattern Specificity

Distinguishing Cardiac Sarcoidosis from Other Cardiomyopathies

• Three-dimensional speckle-tracking radial strain can differentiate cardiac sarcoidosis from dilated cardiomyopathy, with GRS ≤21.1% distinguishing CS from DCM with 70% sensitivity and 88% specificity (AUC 0.79). 8

• Patients with cardiac sarcoidosis show more negative radial strain curves than those with DCM (1.7±2.3 vs 0.1±0.5, p<0.01), providing an additional distinguishing feature. 8

• Global circumferential strain (GCS) is significantly lower in extracardiac sarcoidosis compared with controls (SMD -3.33,95% CI -4.71 to -1.95, P<0.001), though less discriminatory than longitudinal strain. 3

Clinical Implementation Algorithm

When to Perform Strain Imaging

1. All patients with biopsy-proven extracardiac sarcoidosis should undergo speckle-tracking echocardiography with GLS measurement, even with normal conventional echocardiography and ECG. 2, 1

2. Repeat strain imaging every 6-12 months in patients with extracardiac sarcoidosis to detect interval development of cardiac involvement. 5

3. Perform strain imaging in patients with cardiac symptoms (palpitations, syncope, chest pain, dyspnea) and known sarcoidosis, regardless of LVEF. 7

Interpretation Framework

• LV GLS > -16% (less negative): Highly suspicious for cardiac involvement, proceed to cardiac MRI with late gadolinium enhancement. 5, 1

• LV GLS -16% to -18%: Borderline abnormal, consider cardiac MRI and repeat strain imaging in 3-6 months. 5

• RV GLS > -20%: Concerning for right ventricular involvement, which carries increased mortality risk. 7, 1

Integration with Other Modalities

• Cardiac MRI remains the imaging gold standard for confirming cardiac sarcoidosis, with characteristic mid-myocardial and subepicardial late gadolinium enhancement in basal septum and lateral walls. 7

• Strain imaging serves as an effective screening tool to identify which patients require advanced imaging with MRI or PET, given cost and availability limitations of these modalities. 3

• FDG-PET can assess active inflammation and guide immunosuppressive therapy decisions in patients with abnormal strain parameters. 7

Critical Limitations and Pitfalls

Technical Considerations

• Significant vendor variability exists between different ultrasound machines and software versions, requiring serial measurements on the same equipment for accurate comparison. 5

• Image quality must be adequate for speckle-tracking analysis; poor acoustic windows limit strain measurement accuracy. 9

• Strain values are not applicable in patients receiving inotropic agents or mechanical circulatory support, as these interventions alter measurements. 5

Clinical Context Requirements

• Post-cardiac surgery patients may have artifactually reduced septal strain due to paradoxical septal motion, making lateral wall assessment more reliable in this population. 9, 6

• Athletic individuals may have slightly reduced GLS values representing normal physiologic adaptation rather than pathology, requiring clinical correlation. 5

• A single borderline GLS value does not necessarily indicate disease in asymptomatic patients without cardiac risk factors and normal LVEF. 5

Management Implications

Treatment Initiation Triggers

• Reduced LV GLS (<-16%) in extracardiac sarcoidosis patients warrants consideration of corticosteroid therapy (prednisone 40-60 mg daily) even before overt cardiac symptoms develop. 7

• Serial strain monitoring can assess response to immunosuppressive therapy, with improvement in GLS indicating effective treatment. 7

• Failure to improve GLS despite therapy predicts adverse outcomes and may require escalation to alternative immunosuppressants (methotrexate, azathioprine, mycophenolate). 7

Device Therapy Considerations

• Patients with LV GLS > -14% and LVEF <35% are at particularly high risk for sudden cardiac death and require evaluation for implantable cardioverter-defibrillator placement. 7, 1

• Conduction abnormalities occur in 25-30% of cardiac sarcoidosis patients and may require pacemaker implantation, particularly when combined with reduced strain values. 7