P1720Increased evidence of left ventricular myocardial fibrosis in patients with paroxysmal atrial fibrillation and sinus node dysfunction

M.S. Dzeshka, K. Appadoo, E. Shantsila, V.A. Snezhitskiy, G.Y.H. Lip
2017 European Heart Journal  
Atrial fibrillation mechanisms 379 high quality studies that used gain-and loss-of-function models and/or luciferase reporter assays to study miRNA function. Results: We included 9 tissue and 6 plasma explorative studies. Study outcomes were frequently contradictory. Differently expressed miRNAs in AF were generally higher in tissue, but in plasma, miRNA levels were lower in AF. Upregulated miRNAs in tissue described in ≥3 studies were: miR-15b, -21, -24, -30a, -142-3p, -146b, -208b, -223 and
more » ... 99. MiRNAs with decreased plasma levels in ≥3 studies were miR-99b, -150 and -328. Among these miRNAs, 6 were found to function in fibrosis signaling, calcium-or potassium channel regulation (table). Ten miR-NAs described in functional studies lacked supporting evidence from explorative studies. Conclusion: There is increasing evidence for an association between plasma and tissue miRNAs and electrical and structural remodeling in AF. MiRNAs designated by this study were tissue miR-21, -30a, -146b, -208b, -499 and plasma miR-328. However, no miRNA has reached clinical applicability so far and further studies on miRNA function in AF are warranted. Acknowledgement/Funding: Background: Atrial fibrillation (AF), sinus node dysfunction (SND) and heart failure with preserved ejection fraction (HFpEF), all are increasingly prevalent with the ageing population. Myocardial molecular and structural remodeling may be underlying pathological mechanism. Purpose: To assess left ventricular (LV) remodeling and its relation to circulating markers of cardiac fibrosis in patients with paroxysmal AF (pAF) and SND. Methods: We studied 104 patients: 28 patients (median age 68, 50% male) with pAF and SND were compared to 44 patients (median age 63, 59% male) with pAF without SND, and 32 patients (median age 61, 56% male) with hypertension and/or stable coronary heart disease with neither pAF history nor evidence of SND as "disease controls". LV myocardial fibrosis was assessed via calibrated integrated backscatter (cIB) on echocardiography as difference between pericardial and myocardial reflectivity. Using ELISA, levels of galectin 3, interleukin-1 receptor-like 1 (ST2), free active transforming growth factor beta 1 (TGF-β1), and procollagen type III N-terminal propeptide (PIIINP) (all serum), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) (both plasma), were assayed as surrogate biomarkers of cardiac fibrosis. Results: Median [IQR] cIB in patients with pAF and SND was significantly lower (24.1 [21.6-26.8] dB) compared to controls (27.2 [26.5-30.1] dB, p<0.01), but it did not differ from pAF patients with no SND (25.5 [23.5-28.1] dB, p>0.05). ST2, MMP-9, and TGF-β1 levels were significantly higher in patients with pAF and SND compared to other groups (Table) . On multivariable analysis, plasma level of MMP-9 (β=-0.39, p<0.01) and AF history (β=-0.27, p<0.05) were independent predictors of LV cIB (adjusted for age, gender, presence of SND, hypertension and coronary heart disease).
doi:10.1093/eurheartj/ehx502.p1720 fatcat:oxup4zailzgjdcocw5i4ihfhe4