Prognostic Relevance and Lower Limit of the Reference Range of Left Ventricular Global Longitudinal Strain: A Clinical Validation Study.

Summary

A meta-analysis of 47 studies (23,208 healthy subjects) and validation cohorts identified a vendor-agnostic lower limit of normal for GLS at 16%. GLS <16% predicted heart failure hospitalization in asymptomatic at-risk individuals over 6 years and in elderly individuals over 2 years.

Key Findings

• Meta-analysis across 47 studies and 23,208 healthy subjects identified GLS lower limit of normal at 16% across EchoPac, TomTec, and QLab
• Validation in 2,217 healthy adults confirmed 16% as LLN
• GLS <16% associated with increased HF hospitalization: asymptomatic at-risk (OR 5.1 over 6 years) and elderly ≥80 years (OR 3.1 over 2 years)

Clinical Implications

Use a GLS threshold of 16% (absolute) as the lower limit of normal across vendors. Values below 16% warrant closer surveillance for HF, even in asymptomatic patients with preserved EF, especially in elderly cohorts.

Limitations

• Heterogeneity inherent to observational studies and speckle-tracking acquisition protocols
• Prognostic validation cohorts are observational and limited in size for hard outcomes

Future Directions

Prospective multicenter studies should assess how applying the 16% threshold changes management and outcomes, and evaluate longitudinal GLS trajectories and integration with other imaging/biomarkers.