LA structural remodeling is predicted by arterial stiffening independently of conventional risk factors

Background

Left atrium (LA) size and function are powerful biomarkers of cardiovascular outcomes in many diseases. We sought to determine if the expected age-associated increase in arterial stiffness (AS) and left ventricular (LV)-LA afterload leads to corresponding effects on LA function and this can be measured with cardiovascular magnetic resonance (CMR). Additionally, we investigated the significance of these markers in asymptomatic individuals with cardiovascular risk factors (CRF).

Methods

Female subjects from the Twins UK cohort with no overt cardiac disease were prospectively recruited for a CMR study on a 1.5 Tesla scanner (Philips, Best, Netherlands) with tissue characterization (T1 mapping and late gadolinium enhancement). Patients with atrial fibrillation, valvular disease, regional wall motion abnormalities at rest or areas of myocardial enhancement were excluded from the analysis. LA reservoir, conduit and contractile functions were quantified by both fractional volume changes and CMR feature tracking derived strain and strain rate. Additionally, CMR feature tracking derived myocardial deformation indices and pulse wave velocity (PWV) (foot-to-foot methodology), were calculated.

Results

40 female twins were enrolled. Baseline characteristics are shown in table 1. Bivariate analysis showed that LA volume, LA reservoir, conduit and booster function correlated with LV deformation parameters and with PWV, a surrogate marker of AS (p < 0.001 to 0.044). Furthermore, LA function components assessed by fractional volume changes were significantly different in the presence of ≥1 risk factors (p < 0.001 to 0.012). Multivariable regression analysis confirmed that only the conduit and booster components were associated with changes in LV deformation and PWV (figure 1, panel A). Subjects with CRF had lower LA conduit function and higher booster function. We hypothesize that this can be attributed to an increase in atrial afterload in response to increased LV stiffness-AS that occurs with aging but is more pronounced subjects with CRF as is demonstrated by lower LV deformation indices and higher calculated PWV. ROC analysis showed that LA volume and function parameters outperformed LV deformation and AS parameters in the evaluation of subclinical cardiac changes in the presence of CRF (figure 1, panels B and C)

Table 1 Baseline characteristics

Figure 1

Scatter plots (Panel A) showing the relationships between LA-LV deformation parameters and LA-PWV (abbreviations as shown in table 1). GRs (syst), GRSr (diast), and PWV were identified as independent determinants of LA mechanics in individuals with risk factors on multivariate analysis. Panels B and C. ROC curves comparing the sensitivity and specificity of different diagnostic parameters used in the analysis in the presence of cardiovascular risk factors.

Conclusions

LA mechanics correlates with LV deformation parameters and PWV and differs significantly in elderly subjects with CRF compared to their healthy age-matched peers. LA structural remodeling is predicted by AS (as expressed by PWV/LV parameters) independently of conventional CRF, thus supporting the hypothesis of arterial-ventricular-atrial coupling (AVAC). These novel markers of LA performance can potentially uncover abnormal AVAC in patients with CRF but no overt cardiac disease and give valuable insights into ventricular dysfunction beyond standard volumetrics.