Abnormal Global Longitudinal Strain Correlates with Amyloidogenic Light Chain-Induced Cardiac Dysfunction via Direct Myocardial Toxicity in Patients without Significant Amyloid Fibril Deposition

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.3415-3415
• Main Authors: Ferri, Grace M., Villegas Galaviz, Josue, Ajayi, Tinuola, Giadone, Richard, Murphy, George J., Staron, Andrew, Ruberg, Frederick L., Sanchorawala, Vaishali, Edwards, Camille V.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-182520

Introduction: Patients with advanced cardiac AL have high early mortality despite receiving effective plasma cell-directed therapies. Cardiac dysfunction is caused by direct myocardial toxicity from amyloidogenic light chains (LCs) and architectural distortion from amyloid fibril deposition. Diagnosis before significant fibril-induced cardiac dysfunction is critical for improving outcomes. While measuring cardiac biomarkers is standard for risk stratification of patients with newly diagnosed AL, serum concentrations can be impacted by fluid shifts and renal impairment, suggesting a need for complementary biomarkers. Our transcriptomic analysis highlighted dysregulation of myocardial contractility in cardiac cells exposed to amyloidogenic LCs, leading us to hypothesize that there could be clinically measurable differences in cardiac contractility (Ghosh et al., 2023). Global longitudinal strain (GLS) is a sensitive echocardiographic measure of myocardial contractility and may predict survival independent of serum cardiac biomarkers. Since LC-induced cardiac dysfunction via direct myocardial toxic effects is reversible with plasma cell-directed therapy and may represent an early cardiac insult in patients with cardiac AL, we identified and evaluated patients with LC-induced cardiac dysfunction and no clinical or echocardiographic evidence of significant cardiac amyloid fibril deposition to determine clinical features potentially associated with early cardiac AL. Methods: We analyzed the demographic, clinical, and echocardiographic features of patients with non-cardiac biopsy-proven AL amyloidosis and LC-induced cardiac dysfunction seen at the Boston University Amyloidosis Center between January 1, 2011 and March 31, 2023. Direct LC-induced cardiac dysfunction was defined as: (1) elevated cardiac biomarkers (BNP >176 pg/mL or NT-proBNP >899 pg/mL or troponin I >0.033 ng/mL, per institutional reference ranges); (2) normal echocardiographic interventricular septal thickness (