Left atrial structure and function of the amyloidogenic V122I transthyretin variant in elderly African Americans

Abstract

Aims African‐American carriers of the transthyretin (TTR) valine‐to‐isoleucine substitution (V122I) are at increased risk of heart failure, yet many have relatively subtle abnormalities of left ventricular (LV) function. We sought to explore the influence of this mutation on left atrial (LA) structure and function in this population. Methods and results We assessed 1225 genotyped African‐Americans (age range, 67–89 years) participating in the Atherosclerosis Risk in Communities study who underwent echocardiography and were in sinus rhythm at study Visit 5 (2011 to 2013). Six LA parameters [LA maximum/minimum volume index, ejection fraction, and LA reservoir, conduit, and contractile longitudinal strains (LS)] were compared between V122I TTR variant carriers (n = 46) and non‐carriers (n = 1179). LA minimum volume index was significantly greater and LA contractile LS was worse in carriers than non‐carriers (19.5 ± 10.6 mL/m2 vs. 16.3 ± 8.4 mL/m2; 15.0 ± 5.8% vs. 16.8 ± 5.7%, respectively, both P < 0.05). Carriers had a significantly higher number of LA abnormalities than non‐carriers (1.8 ± 2.2 vs. 1.1 ± 1.6, P = 0.009). The number of subjects with at least four LA abnormalities was significantly increased among carriers compared with non‐carriers (27% vs. 12%; odds ratio 2.43; 95% confidence interval 1.06–5.58 after adjusting for age, sex, body mass index, and LV wall thickness and global LS). Conclusions Left atrial enlargement and dysfunction were common in V122I TTR carriers with sinus rhythm than non‐carriers, suggesting that abnormalities of LA function may represent early markers of subclinical disease in these individuals.

Reverse Atrial Remodeling in Heart Failure With Recovered Ejection Fraction

“…Multiple studies have demonstrated that LA dysfunction may precede changes in LA structure. 14 , 15 , 16 , 17 Thus, we speculate that the changes in LA function may be more sensitive than those of LA volume in detecting LA remodeling, which should be investigated in future researche.…”

Arrhythmic Burden in Cardiac Amyloidosis: What We Know and What We Do Not

“…Moreover, speckle tracking allows the detection of differences not only in overt disease manifestation but also in the subclinical setting. Specifically, if, on one side, left atrial dysfunction proves to be more pronounced in ATTR (compared to AL) patients, despite left atrial volumes being comparable [ 22 ], on the other side, the detection of left atrial abnormalities in carriers with a transthyretin valine-to-isoleucine substitution underlines subtle left ventricular remodeling [ 23 ].…”

“…Increased incidence of intracardiac thrombi despite the absence of AF/flutter [ 22 , 23 , 24 , 24 , 25 , 26 ]…”

Atrial amyloidosis: mechanisms and clinical manifestations

“…On the other hand, a role of amyloid‐mediated damage is suggested by pathophysiological considerations, and the evidence of atrial wall thickening and increased stiffness by cardiovascular magnetic resonance (CMR). We may also consider that LA size is the parameter most directly affected by filling pressures, and that LA stiffness (defined as the ratio between E/e′ and LA strain reservoir) is higher than expected based on LA size alone, 6 , 8 again pointing to a role of atrial wall disease.…”

“… 4 , 5 , 6 The right atrium (RA) may be similarly affected. Atrial amyloidosis develops in early stages of AL‐ and ATTR‐CA, 7 , 8 and is associated with an increased risk of supraventricular arrhythmias and thromboembolic events. Furthermore, atrial amyloidosis can be found even in the absence of systemic disease and LV involvement.…”