Increased Left Ventricular Wall Thickness without Increased Mechanical Dispersion: A Distinguishing Feature of Transthyretin Amyloidosis Cardiomyopathy

INTRODUCTION: Life-threatening ventricular arrhythmia (LTVA) is infrequent in patients with transthyretin cardiomyopathy (ATTR-CM) despite severe cardiac dysfunction. We aimed to assess left ventricular mechanical dispersion (LVMD), as a marker of arrhythmia substrate, in ATTR-CM in comparison to other phenotypes with increased left ventricular (LV) wall thickness and in relation to LTVA occurrence. METHODS: Patients with suspected cardiac amyloidosis (CA) and increased LV wall thickness (septal thickness ≥12 mm) were identified. Patients with other types of CA and obstructive hypertrophic cardiomyopathy were excluded. Data from comprehensive clinical assessments, laboratory tests, echocardiography with speckle tracking, and Tc-99m labeled pyrophosphate scintigraphy (PYP) were retrospectively collected from each patient. Diagnosis of ATTR-CM was established based on current recommendations. Longitudinal follow-up was performed over 5 years for LTVA (ventricular tachycardia and sudden cardiac arrest). RESULTS: In ATTR-CM group (n=150) lower LV ejection fraction, impaired global longitudinal strain (GLS), higher LV mass index, smaller end-diastolic volume index and higher relative apical sparing (RAS) were observed compared to the non-amyloid LVH group (n=223). Significantly lower mechanical dispersion (LVMD) was a remarkable feature of ATTR-CM, additive to ESC echocardiography parameters for the differential diagnosis (net reclassification improvement: 0.74). Higher LVMD was associated with increased risk of LTVA, whereas ATTR-CM was associated with a lower risk of LTVA. Mediation analysis further supported the mediating role of LVMD in the association between ATTR-CM and LTVA. CONCLUSION: Lower LVMD seems to be a distinguishing feature of ATTR-CM in association with infrequent LTVA despite severe increased LV wall thickness.