Subclinical left atrial dysfunction profiles for prediction of cardiac outcome in the general population
Authors: Cauwenberghs N , Haddad F , Sabovcik F , Kobayashi Y , Amsallem M , Morris D.A , Voigt J.U , Kuznetsova T 
Published: November 2020

Abstract

Background
Echocardiographic screening for subclinical left atrial (LA) dysfunction might enhance the prediction of cardiac diseases such as atrial fibrillation (AFib) in the community. To date, however, outcome-driven definitions of early-stage LA dysfunction remain scarce.

Purpose
In a large population sample, we sought to extract outcome-driven thresholds for echocardiographic indexes of LA function to define subclinical left atrial (LA) dysfunction and assess the prognostic value of these echocardiographic criteria for prediction of cardiac events.

Methods
In 1306 community-dwelling individuals (mean age, 50.7 years; 51.6% women), we assessed LA function and left ventricular (LV) global longitudinal strain (LS) by echocardiography. Using receiver-operating curve threshold analysis, we derived outcome-driven cut-offs for LA emptying fraction (LAEF) and LA reservoir strain (LARS) that best balanced the cardiac event prediction (i.e. cut-offs yielding the highest Youden index (=sensitivity+specificity-1)). Next, we constructed LA dysfunction profiles and integrative LA/LV strain profiles based on the extracted cut-offs for LAEF and LARS and a validated definition of impaired LV global LS. We assessed the prognostic performance of these profiles in predicting the incidence of cardiac events and AFib (mean follow-up, 8.5 years).

Results
During follow-up, 93 participants experienced a cardiac event (8.3 events/1000 person-years) and 27 developed AFib (2.3 events/1000 person-years). LAEF&lt;55% and LARS&lt;23% yielded the highest Youden indexes and thus provided the most balanced prediction of incident AFib. When applying these cut-offs, abnormal LAEF and LARS were respectively present in 27.0% and 18.1% of the cohort. Abnormal LARS was independently associated with higher risk for cardiac events (hazard ratio (HR) versus normal LA phenotype: 2.11, P=0.0021). Both abnormal LAEF (HR: 2.57) and abnormal LARS (HR: 3.28) predicted incident AFib (P≤0.029). As compared to subjects free from any LA dysfunction, those with both LAEF&lt;55% and LARS&lt;23% had a significantly higher risk to develop cardiac events (HR: 2.10; P=0.014) and AFib (HR: 6.45; P=0.0036). Of the integrative LA/LV strain profiles, the concomitant presence of an impaired LARS and LV global LS independently elevated the risk for cardiac events (HR: 2.81; P=0.0012) and AFib (HR: 4.36, P=0.0071) as compared to normal counterparts. Both the degree of LA dysfunction and the integrative LA/LV strain profiles improved the prognostic accuracy beyond clinical risk models and risk scores.

Conclusions
We validated population-based and outcome-driven definitions of subclinical LA dysfunction predicting cardiac events independent of conventional risk factors. Echocardiographic screening for subclinical LA and LV systolic dysfunction might enhance the prediction of cardiac diseases such as AFib in the community, empowering clinicians to timely intervene with the disease development.
Prediction of cardiac events

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders, Internal Funds KU Leuven