Regional distribution of myocardial work predicts adverse outcomes in hereditary transthyretin cardiac amyloidosis
J C Campos Barba, J Armenta Rodriguez, J A Viana Rojas, C Orihuela Sandoval, G Payro Ramirez, A G Bautista ViverosAbstract
Background
Hereditary transthyretin cardiac amyloidosis (hATTR-CM) is a progressive infiltrative cardiomyopathy characterised by heart failure with preserved ejection fraction and marked phenotypic variability according to genotype. Most prognostic echocardiographic data derive from wild-type or myxed cohorts, limiting applicability to genetically distinct populations. Myocardial work indices integrate left ventricular deformation with afterload and may provide a more physiologically relevant assessment of myocardial performance in amyloidosis, particularly in the presence of autonomic dysfunction and altered loading conditions.
Purpose
To evaluate the prognostic value of global myocardial work index (GWI) and derived myocardial work parameters in a genetically characterised cohort of patients with hATTR-CM.
Methods
Retrospective longitudinal study including 42 adults with confirmed hATTR-CM. Comprehensive echocardiography with pressure–strain loop analysis was performed to derive GWI, global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), and the relative apical-to-basal work ratio (RAB). The primary composite endpoint included heart failure hospitalisation, ventricular arrhythmia or device implantation, and all-cause mortality. Prognostic performance was assessed using ROC curves and Kaplan–Meier survival analysis.
Results
Mean age was 47.5 years; 59% were female. A single predominant pathogenic variant accounted for 70% of cases (Ser70Arg), reflecting genetic homogeneity within this cohort. Despite preserved left ventricular ejection fraction (median 60%) and relatively early functional class (50% in NYHA II), global longitudinal strain was already reduced (mean 13.9%), indicating subclinical systolic impairment. During a median follow-up of 25 months (IQR 9–35), 17 patients (40%) reached the composite endpoint. Patients with events were older, had higher natriuretic peptide levels and more advanced neurological impairment. They demonstrated lower global longitudinal strain (11.9% vs 15.3%, p<0.01), higher E/e′, and significantly reduced GWI and GCW (p<0.04). GWI predicted events (AUC 0.74; cut-off 1170 mmHg%; sensitivity 82%, specificity 68%). RAB demonstrated the highest discriminatory capacity (AUC 0.77; cut-off 1.62; sensitivity 76%, specificity 84%), outperforming global indices and showing early and significant separation of Kaplan–Meier curves (log-rank p=0.001).
Conclusion
In this genetically characterised hATTR-CM cohort, myocardial work indices were associated with adverse outcomes despite preserved ejection fraction and early clinical stage. The relative apical-to-basal work ratio showed superior prognostic performance compared with global myocardial work, suggesting that regional distribution of myocardial work captures disease heterogeneity and may enhance risk stratification in hereditary amyloid cardiomyopathy.