484 Echocardiographic patterns in patients with apolipoprotein AI amyloidosis
Authors: Tomasoni Daniela , Aimo Alberto , Lombardi Carlo Mario , Cuni Simone , Panichella Giorgia , Fabiani Iacopo , Vergaro Giuseppe , Passino Claudio , Emdin Michele , Metra Marco 
Published: December 2021

Abstract

Aims
Hereditary amyloidosis are rare diseases characterized by extracellular deposition of insoluble fibril proteins in target organs disrupting their structure and function. The APOA1 gene encodes the precursor of apolipoprotein AI (ApoAI), whose mature form is the major component of high-density lipoproteins. There are some clusters of ApoAI amyloidosis (AApoAI) worldwide, including in the Lombardy and Veneto regions. Patients with AApoAI often present with chronic kidney disease, liver and spleen enlargement, with occasional involvement of the heart, peripheral nervous system, and other organs. Patterns of cardiac disease in AApoAI have never been systematically investigated.

Methods and results
We examined all patients with an established diagnosis of AApoAI referred to a dedicated outpatient clinic in Brescia from 2010 to 2020. The cardiac screening included a transthoracic echocardiogram with 2D speckle-tracking analysis. One-hundred and eighty-nine patients were evaluated [n = 102 (54%) men, median age 55 years (interquartile range 42–67)]. Renal disease was present in 39% and liver disease in 31%. Almost all patients were in sinus rhythm (96%). Median left ventricular ejection fraction (LVEF) was 60% (55–66), and just 2% of patients had LVEF &lt;50%. Diastolic function was preserved, with E/e′ ratio of 7 (6–10). Overall, patients did not display a prominent LV hypertrophy, with median interventricular septal thickness of 11 mm (9–12), a posterior wall thickness of 9 mm (8–11), and a LV mass index of 92 g/m2 (74–111). Global longitudinal strain [−19% (−21 to − 17)], and the mass to strain ratio (MSR) [10.0 (6.8–12.1)] were within normal limits. Ten percent of patients displayed apical sparing, and 19% had a ‘granular sparkling’ appearance of the interventricular septum, which are both echocardiographic red flags of cardiac amyloidosis. Right ventricular (RV) function was preserved [median tricuspid annular plane systolic excursion of 23 mm (20–26)], with a borderline RV free wall thickness [6 mm (5–8)]. A pericardial effusion was present in 11%. Moderate to severe mitral, aortic or tricuspid regurgitation or aortic stenosis were found in 11%, 4%, 6% and no patients, respectively. We found moderately strong correlations between age and several echocardiographic findings, namely: IVS (P &lt; 0.001, r = 0.484), LVMI (P &lt; 0.001, r = 0.459), E/e′ (P &lt; 0.001, r = 0.501), and RV free wall thickness (P &lt; 0.001, r = 0.459). Absolute GLS tended to decrease with age (P &lt; 0.001, r = 0.380), and MSR to increase (P &lt; 0.001, r = 0.357).

Conclusions
In the largest series of patients with AApoAI so far, minor signs of cardiac disease emerged from transthoracic echocardiography. Nonetheless, some red flags of cardiac amyloidosis were found in some patients. Furthermore, the correlations between age and echocardiographic findings suggested a progressive increase in wall thickness, a decline in systolic and diastolic function, and a greater uncoupling between LV mass and contractility over time.