Fig 1.
Typical left atrial strain (LAS) and histological findings in a patient with PAF (Aa, Ba) and a patient with atrial fibrillation (AF) (Ab, Bb). Aa and Ab: Quad view of longitudinal left atrial (LA) strain by 2DSTE. Elastica van Gieson stain (EVG), and immunohistochemical staining of collagen type 1a are also shown for each patient. Ba and Bb: Two typical LA strain images from 4-chamber (4CH) and 2-chamber (2CH) apical views obtained from a patient with PAF (Ba) and a patient with AF (Bb). The mean values were averaged for 6 segments in the 4CH view (left part) and 6 segments in the 2CH view (right part), as shown in the lower part. LASr, LA reservoir strain; LASct, LA contractile strain; LAScd, LA conduit strain.
Table 1.
Characteristics of the patients.
Fig 2.
Relationships between left atrial strain (LAS) and echocardiographic findings (LAVI (bp), E/e’, LVEF (bp).
The data of mLASr and mLAScd were obtained from 118 patients including PAF and AF. The data of mLASct were obtained from 84 patients with SR patients including PAF. mean LASr value (mLASr), LAScd (mLAScd), LASct (mLASct)). R- and P-value are shown. *P<0.05, **P<0.01, ***P<0.001.
Fig 3.
Comparison of echocardiographic parameters and gene expression level between patients with SR including PAF and those with AF.
A: Comparison of echocardiographic parameters. SR including PAF (blue, n = 84), AF (red, n = 34). B: ROC to identify the optimal cut-off level of echocardiographic findings to detect AF (n = 118). C: Comparison of ANP, and fibrosis-related gene expression level in between patients with PAF (n = 23–24) and those with AF (n = 33–35). PAF (blue), AF (red). *P<0.05, ***P<0.001.
Fig 4.
Correlations among atrial gene expression level including ANP, and fibrosis-related gene expression in total patients.
A: Correlations among atrial gene expression level including ANP, and fibrosis-related gene expression in total patients receiving LA resection (n = 57–59). The R-value and P-value among genes are indicated. *P<0.05, **P<0.01, ***P<0.001. The orange area shows statistical significance. B: Correlations between COL1A1 and fibrosis-related gene expression level (ANP, COL3A1, FN1, TGFB1) in total patients receiving LA resection (n = 57–59). C: Correlations between COL1A1 and fibrosis-related gene expression level (ANP, COL3A1, FN1, TGFB1) in PAF patients (n = 23–24). *P<0.05, **P<0.01, ***P<0.001.
Fig 5.
The univariate regression analysis with log (COL1A1) expression level as the dependent variable and fibrosis-related gene expression as the independent variable.
The adjusted R-squared value (R2) is shown. The data were obtained in 57–59 patients receiving LA resection. Pro-fibrogenic cytokine genes (TGFB1, EDN1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ECM degradation-related genes (MMP2, TIMP1, TIMP2), inflammation-related genes (NLRP3, IL1B, MCP-1, TNF), angiotensin-related gene (ACE), apoptosis-related gene (BAX). All data are P<0.001.
Fig 6.
Relationships between COL1A1 mRNA expression level and echocardiographic parameters.
A: Relationships between COL1A1 mRNA expression and clinical data (age, sex, BMI) and echocardiographic parameters in PAF patients (n = 20) and total patients (n = 52) receiving LA resection. R- and P–values are shown. *P<0.05 B and C: Relationships between COL1A1 mRNA expression level and LAVI (bp) or mLASr in total patients (B, n = 52) and PAF patients (C, n = 20) receiving LA resection. *P<0.05.
Table 2.
Comparison of gene expression levels and echocardiographic parameters between PAF patients with low mLASr and high LASr.
Fig 7.
Correlation matrix between clinical data (age, sex, BMI), echocardiographic findings and fibrosis-related gene expression level in PAF (A) and AF (B) patients. The data were obtained from PAF patients (n = 19–20) and AF patients (n = 30–32) receiving LA resection. R–value and P–value in mLASr, mLAScd, and mLASct are shown. *P<0.05, **P<0.01, ***P<0.001. Significant negative relationships (R = –0.25 ~ –0.5, R = –0.5 ~ –0.75) are shown in green area, and positive relationships (R = 0.25~ 0.5, R = 0.5 ~ 0.75) are shown in orange area.
Fig 8.
Graphic abstract of the study.
SR, sinus rhythm; PAF, paroxysmal atrial fibrillation; AF, atrial fibrillation; ANP, atrial natriuretic peptide; LASr, left atrial reservoir strain; LAVI, left atrial volume index; COL collagen; EVG, Elastica van Gieson staining.