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DECLARATION OF CONFLICT OF INTEREST Left atrium size and incidence of new-onset atrial fibrillation in essential hypertensives. A 6 years prospective study D.TSIACHRIS, C.TSIOUFIS, A.KASIAKOGIAS, M.POULAKIS, M.ALMYROUDI, D.ARAGIANNIS, K.KINTIS, I.ANDRIKOU, I.ANASTASOPOULOS, C.STEFANADIS First Cardiology Clinic, University of Athens Hippokration Hospital, Athens, Greece Epidemiology Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, occurring in 1–2% of the general population. The prevalence of AF increases with age, from <0.5% at 40–50 years, to 5–15% at 80 years Heart 2001;86:516–521 JAMA 2001;285:2370–2375 Clinical events (outcomes) affected by AF ESC Guidelines 2010 The annual cost per patient is close to €3000 AF is an extremely costly public health problem, with hospitalizations as the primary cost driver (52%), followed by drugs (23%), consultations (9%), further investigations (8%), loss of work (6%), and paramedical procedures (2%) Am Heart J. 2004;147:121– 6 Heart. 2004;90:286–92 Anatomical and Electrophysiological Substrates Promoting AF Diseases Anatomical Cellular EP Hypertension Atrial dilatation Myolysis Conduction abnormalities Heart Failure PV dilatation Apoptosis ERP dispersion Coronary artery disease Fibrosis Channel expression changes Ectopic activity Valvular disease Left atrium (LA) and CV risk Increased LA size is closely related to atrial fibrillation Henry WL, et al. Circulation. 1976; stroke, once atrial fibrillation is manifested Cabin HS, et al. Am J Cardiol. 1990; Index of future adverse cardiovascular events LA volume or diameter? 2-D derived LA volume provides a more accurate measure of the true size of the LA than LA diameter, although both LA size parameters have been shown to be markers of CV risk Lester SJ, Am J Cardiol 1999 LA size and SR? LA volume is a more robust marker of CV events than LA area or diameter in subjects with sinus rhythm In patients with AF, the predictive utility of LA size seems unsatisfactory Tsang et al, JACC 2006 LA size and diastolic function Atrial size as assessed by LAVI has been correlated with the severity of Diastolic Dysfunction, and this association was still apparent after controlling for pertinent covariates Pritchett et al, JACC 2006 Positive association of LAVI with BNP in untreated essential hypertensives Tsioufis et al, J Hypertens 2006 Study purpose The aim of our study was to compare the predictive role of LA size, as determined either by LA diameter or by LA volume index, for the incidence of new-onset AF. Study population We prospectively followed up for a median period of 6 years (IQ 5-6.6 years) 782 uncomplicated hypertensives without history of AF episodes aged 58.1±10 years Study design All subjects had at least one visit annually and at entry underwent complete echocardiographic study. Cardiac ultrasound LV mass was calculated with the method of Devereux et al and normalized either for body surface area (BSA) or for height2.7 to obtain LV mass index Relative Wall Thickness (RWT) was calculated at end diastole according to the following equation: RWT = (interventricular septum thickness + posterior wall thickness) / (LV end-diastolic diameter) LA diameter LA diameter was measured by 2Dguided M-mode echocardiography obtained in the parasternal shortaxis view at the base of the heart LAV = π/6 (SA1 x SA2 x LX) SA1 : M-mode LA diameter SA2 and LX : short- and long-axis in the apical 4chamber view at ventricular end-systole LA volume was indexed for body surface area to estimate LA volume index (LAVI) LAVI = LAV / BSA Laboratory parameters Metabolic profile, serum creatinine levels (sCr) and estimated creatinine clearance (CrCl) (according to Cockroft-Gault formula) were assessed from a morning blood sample. CKD was defined based on estimated CrCl between 15 and 59 ml/min. The incidence of new-onset AF over the whole followup period was 5% (22 patients with paroxysmal AF and 17 patients with permanent AF). new onset AF Free of AF Clinical characteristics Patients with AF (n=39) Patients without AF (n=743) p Age (years) 66.7±8 57.6±10 <0.001 Males (%) 59 47 0.14 28.7±3.6 28.6±4.1 0.84 99.9±8 97±11 0.048 15 10 0.37 Office SBP (mmHg) 144.3±15 142.2±16 0.46 Office DBP (mmHg) 84.7±9 90.0±10 0.002 Office PP (mmHg) 59.6±13 52.2±14 0.002 BMI (Kg/m2) Waist (cm) Diabetics (%) Cardiac ultrasound characteristics Patients with AF (n=39) Patients without AF (n=743) p LVMI-BSA (g/m2) 121.5±29 107.6±27 0.002 LVMI-height (g/m2.7) 49.4±12 44.0±11 0.003 0.46±0.08 0.43±0.07 0.018 LAD (mm) 42.5±5.3 38.0±4.7 <0.001 LAVI (ml/m2) 26.8±8.3 22.7±6.7 0.001 E (cm/s) 0.82±0.26 0.75±0.17 0.02 E/A 1.03±0.37 0.97±0.26 0.13 Em 7.0±2.7 7.9±2.8 0.07 Em/Am 0.90±0.4 0.83±0.4 0.35 E to Em 13±6.3 10.6±4.6 0.004 RWT Laboratory parameters Patients with AF (n=39) Patients without AF (n=743) p Glucose (years) 102.8±19 102±20 0.80 Serum creatinine (mg/dl) 1.04±0.24 0.97±0.3 0.19 76.6±25 90.2±29 0.006 27.7 12.7 0.1 5.62±1.6 5.16±1.5 0.07 Creatinine clearance (ml/min) CKD (%) Uric acid (mg/dl) Predictive role of LA diameter In successive multivariate Cox regression models age (HR 1.076, p<0.001), left ventricular mass index (HR 1.015, p=0.013) LA diameter (HR 1.201, p<0.001) o instead of LAVI (HR 1.042, p=0.07) turned out to be independent predictors of new-onset AF. Regression model including LAD Variables in the Equation Wald Sig. Exp(B) 95,0% CI LowerUpper Age 14,814 0,000 1,076 1,037 1,118 Off PP 0,872 0,350 1,011 ,988 1,034 LVMI 6,214 0,013 1,015 1,003 1,026 LAD 31,709 0,000 1,201 1,127 1,280 Regression model including LAVI Variables in the Equation B Wald Sig. Exp(B) 95,0% CI Lower Upper Age 0,021 8,772 0,003 1,065 1,110 Off PP 0,013 1,109 0,292 1,014 ,988 LVMI 0,007 2,054 0,152 1,009 1,023 LAVI 0,023 3,362 0,067 1,042 ,997 1,021 1,039 ,997 1,089 Limitations Other formulas Simpson’s Area-length Volume is more difficult to measure? No data for inter or intra observer variability LA size assessed either by its diameter or by its volume is closely related to LV mass index irrespective from LV geometric pattern in the early stages of essential hypertension. LA diameter: easier and better Uncomplicated hypertensives with new-onset AF are characterized by significantly increased LA diameter and LA volume indexed for body surface area. Although LAVI has been generally considered a more accurate estimate of LA size, LA diameter turned out to be a more powerful predictor of newonset AF in the setting of essential hypertension.