Impaired left atrial reservoir and conduit strain in patients with atrial fibrillation and extensive left atrial fibrosis

Background Atrial fibrillation (AF) is associated with profound structural and functional changes in the atria. In the present study, we investigated the association between left atrial (LA) phasic function and the extent of LA fibrosis using advanced cardiovascular magnetic resonance (CMR) imaging techniques, including 3-dimensional (3D) late gadolinium enhancement (LGE) and feature tracking. Methods Patients with paroxysmal and persistent AF (n = 105) underwent CMR in sinus rhythm. LA global reservoir strain, conduit strain and contractile strain were derived from cine CMR images using CMR feature tracking. The extent of LA fibrosis was assessed from 3D LGE images. Healthy subjects underwent CMR and served as controls (n = 19). Results Significantly lower LA reservoir strain, conduit strain and contractile strain were found in AF patients, as compared to healthy controls (− 15.9 ± 3.8% vs. − 21.1 ± 3.6% P < 0.001, − 8.7 ± 2.7% vs. − 12.6 ± 2.5% P < 0.001 and − 7.2 ± 2.3% vs. − 8.6 ± 2.2% P = 0.02, respectively). Patients with a high degree of LA fibrosis (dichotomized by the median value) had lower reservoir strain and conduit strain compared to patients with a low degree of LA fibrosis (− 15.0 ± 3.9% vs. − 16.9 ± 3.3%, P = 0.02 and − 7.9 ± 2.7% vs. − 9.5 ± 2.6%, P = 0.01, respectively). In contrast, no difference was found for LA contractile strain (− 7.1 ± 2.4% vs. − 7.4 ± 2.3%, P = 0.55). Conclusions Impaired LA reservoir and conduit strain are present in AF patients with extensive atrial fibrosis. Future studies are needed to examine the biologic nature of this association and possible therapeutic implications.

Electrograms from the coronary sinus as a predictor for the outcome of a re-do pulmonary vein isolation

Background Voltage signals in the coronary sinus (CS) have been associated with the presence of left atrial fibrosis. The aim of the present study was to evaluate the value of CS voltage signals as a predictor for atrial fibrillation (AF)-recurrence-free outcome of pulmonary vein isolationprocedures (PVI) in patients after a first unsuccessful cryo-balloon PVI. Method We collected recordings from a diagnostic catheter positioned in the CS from 282 consecutive atrial fibrillation patients undergoing a re-dopulmonary vein isolation using a 3D mapping system. The patients were followed-up (Holter ECG and telephone calls) for at least one year (median of 14 months). Results Of the 282 patients (male 72%, mean age 63±10.8 years, 61% persistent AF) AF recurrences were documented in 152 pts (54%)with a signal amplitude in the proximal CS position of 2.4 mV ± 1.5 mV. Patients free of AF-recurrence showed significantly higher signal amplitude of 2.9 mV ± 2.1 mV (P&lt;0,05). A CS voltage &lt;0.53mV could predict recurrences of AF with a sensitivity of 94.7% (95% CI 89.3% – 97.8%) and specificity of 8.6% (95% CI 4.6% – 14.8%; PLR 1.04; AUC 0.55). Conclusion Voltage signals in the CS, as a marker for left atrial fibrosis, are associated with the outcome of PVI. A voltage threshold of &lt;0.53mV can predict AF recurrences with a high sensitivity. However, the predictive value for AF recurrences is not high due to the low specificity of this test. FUNDunding Acknowledgement Type of funding sources: None.

Molecular mechanisms of left atrial fibrosis development in patients with atrial fibrillation and metabolic syndrome: what biomarkers should be used in clinical practice?

Aim. To determine the blood concentration of fibrosis biomarkers in patients with atrial fibrillation (AF) in combination with metabolic syndrome (MS) and to analyze the relationship with myocardial fibrosis.Material and methods. This cross-sectional case-control study included 547 patients aged 35 to 65 years: experimental group — patients with MS (n=373), of which 202 patients had AF; comparison group — AF patients without MS (n=110); healthy subjects without cardiovascular diseases and metabolic disorders (n=64). Patients with AF and MS who underwent electroanatomic mapping before pulmonary vein isolation (n=79) were assessed for left atrial (LA) fibrosis severity.Results. It was found that the blood concentration of circulating profibrogenic biomarkers in patients with AF and MS is higher than in patients with AF without MS: aldosterone (135,1 (80,7-224,1) and 90,1 (68,3-120,3) pg/ml, p<0,0001), galectin-3 (10,6 (4,8-15,4) and 5,8 (4,8-8,3) pg/ml, p=0,0001), GDF15 (938,3 (678,3-1352,1) and 671,0 (515,7-879,5) pg/ml, p=0,001), TGF-beta-1 (4421,1 (2513,5-7634,5) and 2630,5 (2020,7-3785,4) pg/ml, p=0,001), CTGF (167,8 (78,9-194,3) and 124,3 (74,4-181,9) pg/ml, p<0,0001), PIIINP (88,5 (58,6120,4) and 58,9 (40,7-86,1) ng/ml, p<0,0001), PINP (3421,4 (1808,1-4321,7) and 2996,1 (2283,8-3894,3) pg/ml, p<0,0001). Patients with paroxysmal AF have higher concentrations of TGF-beta1, CTGF and PINP than patients with persistent and permanent AF. In patients with persistent AF and MS, the concentrations of galectin-3, aldosterone, and PIIINP were higher than in patients with paroxysmal AF, while in patients with permanent AF, they were significantly lower. The plasma concentration of galectin-3 positively correlated with levels of PINP (p=0,465, p<0,0001), PIIINP (p=0,409, p<0,0001), GDF-15 (p=0,369, p<O,O001), CTGF (p=0,405, p<0,0001). According to multivariate regression, of all studied biomarkers, GDF-15 had a greater effect on PIIINP concentration (в=0,234, p=0,038), and galectin-3 — on PINP (в=0,248, p<0,021). Positive correlations of the severity of left atrial fibrosis with the concentration of galectin-3 (p=0,563, p<0,0001), PINP (p=0,620, p<0,0001), TGF-beta-1 (p=0,390, p<0,0001) and CTGF (p=0,551, p<0,0001). According to linear multivariate regression, the most significant effect on LA fibrosis severity among the studied biomarkers is exerted by galectin-3 (в=0,432, p<0,0001), PINP (в=0,343, p=0,001) and PIIINP (в=0,286, p=0,008).Conclusion. An increase in the blood concentration of profibrogenic biomarkers galectin-3, TGF-beta-1, CTGF, PIIINP, and PINP is associated with an increase in LA fibrosis severity and probably has a pathogenetic role in increasing the AF risk in patients with MS.

Atrial tissue characterization by cardiac magnetic resonance and high-density mapping in patients with atrial fibrillation

Funding Acknowledgements Type of funding sources: None. BACKGROUND Left atrial fibrosis is a marker of atrial disease and it has an important role in the pathophysiology of atrial fibrillation (AF). Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is an emerging tool to detect left atrial fibrosis. However, data on the correlation between LGE-CMR detected fibrosis and low voltage areas to define fibrotic tissue is scarce. PURPOSE To assess the correlation and degree of concordance between LGE-CMR and high-density bipolar voltage mapping for the identification of left atrial abnormal tissue. METHODS Seven patients scheduled for AF ablation (including first and redo procedures) underwent a preprocedural 1.5 Tesla LGE-CMR including left atrial 3D inversion-recovery steady-state free precession sequence (ECG and respiratory triggering) 20 minutes after the injection of 0.2 mmol/kg of gadobutrol. A high-density electroanatomical voltage mapping was acquired with a 16-electrode grid configuration mapping catheter during sinus rhythm. LGE-CMR studies were analyzed off-line with an advanced image post-processing tool (ADAS 3D). Atrial wall intensity was normalized to blood pool, obtaining an image intensity ratio (IIR) value for each CMR point of the 3D model. High-density bipolar voltage maps and LGE-CMR 3D left atrial reconstruction were merged (figure, panel A). Voltage points were projected to the LGE-CMR left atrial 3D model, allowing point-by-point correlation analysis between voltage (log transformed due to non-normal distribution) with IIR. Left atrial fibrosis area and percentage were quantified using the standard cut-off values (bipolar voltage &lt;0.5mV and IIR &gt;1.2). We assessed the degree of concordance for normal and abnormal (fibrosis) tissue classification between the two techniques using different cut-off values (&lt; 0.5mV and &lt;1mV for bipolar voltage and &gt;0.9, &gt;1, &gt;1.1 and &gt;1.2 for IIR). RESULTS The average fibrosis area detected with LGE-CMR was lower than that detected with high-density bipolar voltage, using standard cut-off values (18.6 ± 5.7 cm2 vs. 40.6 ± 12.5 cm2, p = 0.13 respectively). There was a poor global point-by-point correlation between log-transformed voltage and IIR was r=-0.093, p &lt; 0.001 (figure, panel B). The best concordance was obtained when using bipolar voltage and IIR of 0.5mV and 1.2, respectively (64.7 %; Kappa 0.101). However, the highest kappa index (0.142) for concordance was achieved with cutoff values of bipolar voltage &lt;1mV and IIR &gt;1, with an agreement percentage of 54.6%. CONCLUSIONS Left atrial tissue characterization between LGE-CMR and high-density bipolar voltage mapping showed significant but poor point-by-point correlation. Although the highest concordance was obtained using standard cutoff values, the Kappa index was best when applying non-standard cutoffs (1mV for bipolar voltage and &gt;1 for IIR). Abstract Figure.

Left atrial fibrosis: an essential hallmark in chronic mitral regurgitation

Chronic mitral regurgitation (MR) is the second valvular heart disease for incidence, which worsening severity gradually affects all cardiac chambers and leads to poor outcome if untreated. The recent development of minimally invasive surgical techniques and percutaneous intervention has reduced the operative risk, allowing a more confident referral of these patients for intervention. Therefore, there is a growing need of reliable markers to select the best therapeutic strategies and to identify the optimal timing for intervention. Myocardial fibrosis (MF) gradually occurs as a result of left atrial and ventricular (LA and LV) remodeling due to MR pressure and volume overload. It has been identifi ed as an index of clinical outcome and arrhythmic risk in patients with MR. Particularly, the assessment of LA fi brosis not only allows to define different MR etiology, but also was associated with prognosis and atrial fibrillation (AF) burden. Nowadays, noninvasive estimation of MF is possible through the use of advanced imaging modalities, particularly cardiac magnetic resonance and speckle tracking echocardiography. This review discusses the role of LA fibrosis as a diagnostic and prognostic marker in patients with MR and its quantification by noninvasive multimodality cardiac imaging.