1064 Ventricular function: mechanisms P5708 | BEDSIDE Alterations of monocyte subsets in chronic heart failure patients in association with changes in epigenetic regulation K. Kaminski 1 , M. Moniuszko 2 , M. Rusak 3 , M. Jasiewicz 1 , K. Ptaszynska Kopczynska 1 , M. Jeznach 2 , A. Lisowska 1 , M. Witkowski 1 , A. Bodzenta Lukaszyk 2 , W.J. Musial 1 . 1 Medical University of Bialystok, Department of Cardiology, Bialystok, Poland; 2 Medical University of Bialystok, Department of Allergology and Internal Diseases, Bialystok, Poland; 3 Department of Haematological Diagnostics, Medical University of Bialystok„ Bialystok, Poland Chronic heart failure (CHF) is closely with associated altered inflammatory re- sponses. Their mechanisms has not been fully elucidated, but there is support for the notion that the specific subsets of monocytes may play a crucial role. Here we aimed to investigate whether CHF is associated with alterations of dis- tribution of different monocyte subsets, namely classical CD14++CD16-, inter- mediate CD14++CD16+, and non-classical CD14+CD16++. Classical monocytes are involved in phagocytosis and resolution of inflammation, a minor subset of macrophage-like CD16-positive monocytes (mostly non-classical) is capable of driving and modulating inflammatory processes by secretion of TNFα, tissue fac- tor or ACE. Moreover, we attempted to explain these changes by investigating epigenetic regulation. We performed a clinical and immunologic analysis of 29 CHF patients and 34 healthy age and gender matched controls. Abovementioned monocyte subsets were analyzed by flow cytometry. Methylation of 94 proinflammatory genes in nu- clear blood cells was assessed using restrictase digestion based assay. In 8 CHF and 14 control serum samples, circulating microRNA regulating inflammatory re- actions were assessed (miR-20a. miR-21, miR146a, miR199), using RT-PCR. We demonstrated that monocytes of CHF patients are significantly enriched in non-classical subset as compared to healthy subjects [6.76% (4.16-9.87) vs. 3.57% (2.48-5.27), respectively; p<0.001]. Similarly, although to a lesser ex- tent, CHF patients presented with greater frequencies of intermediate monocytes [13.2% (6.76-36.1) vs. 8.01% (4.63-15.1), p=0.013]. In contrast, percentages of classical monocytes were significantly less in CHF patients than in healthy con- trols [70.6% (42.4-80.1) vs. 83.1% (77.0-87.1), respectively; p<0.001]. Median level of methylation of proinflammatory genes was higher in patients with CHF 0.4% vs 0.09%, with particular methylation increase of Mapk1 (100% vs 0), IL17 receptor A (25% vs 2%) and NFATc3 (10.1% vs 0.6%) genes. Interestingly, CD14 was severely hypermethylated in controls (99.8%) and much less in CHF (50%). CHF patients had lower serum expression of miR-146a (55.8% of controls) and miR-20a (10.5% of controls) and higher of miR199a (221% of controls) and miR- 21 (344% of controls). Our data indicate that CHF is associated with accumulation of more mature im- munomodulatory monocyte subsets. The observed phenotype may be result of epigenetic effects of blood cells and altered expression of circulation miRNA. Based on our results we could hypothesize that all monocyte subsets are closely implicated in inflammatory processes due to CHF P5709 | BEDSIDE Cardiac transthyretin (ATTR) amyloidosis - clinical and echocardiographic findings from the largest single cohort worldwide K.S. Patel, J.H. Pinney, S. Sachchithanantham, S. Mahmood, A.D. Wechalekar, H.J. Lachmann, J.D. Gillmore, P.N. Hawkins, C.J. Whelan. UCL Medical School, National Amyloidosis Centre, Division of Medicine, Royal Free Campus, London, United Kingdom Purpose: Cardiac transthyretin (ATTR) amyloidosis, also known as senile sys- temic/cardiac amyloidosis, is a rarely diagnosed late onset progressive cardiomy- opathy. Clinical features and outcome data have been characterised only in small groups of patients. Various observations suggest that it may in fact be far more common, and several promising specific new therapies, including transthyretin stabilizers and RNA inhibitors, are now in clinical development. Our aim here was to review and better characterise the clinical features of the disease in a large single centre series. Methods: More than 200 patients have been diagnosed at our UK tertiary cen- tre during the past 5 years, comprising the largest cohort worldwide. Analyses of clinical data and echocardiography performed at our centre in the first 155 pa- tients are presented here, and will be updated to include all cases prior to the ESC Congress. Survival was estimated using Kaplan-Meier analysis. Results: The number of new patients has increased year on year, from 16 in 2007 to 60 in 2012. Of 155 patients, 144 were male (93%). Median age at diagnosis was 77 yr (IQ range 72-81) and at death was 81 yr (IQ range 77-84). Twenty three patients (15%) were younger than 70 yr at diagnosis. Forty five patients have died. Median survival was 51.2 months (95% CI 40.9 to 67.5). Sixty seven (43%) patients had atrial fibrillation at diagnosis. Median serum NT-pro BNP at diagnosis was 329pmol/L (IQ range 208-658), and serum Troponin-T was elevated in 131 (86%) patients. Transthoracic echocardiography showed median EF of 48% (IQ range 40-55), median IVSd 1.7cm (IQ range 1.5-1.8) and median LVPWd 1.7cm (IQ range 1.5-1.8). Median E/E’ was 15.7 (IQ range 12.2-19.3), lateral S’ TDI 0.05m/s (IQ range 0.04-0.06) and septal S’ TDI 0.04 m/s (IQ range 0.03-0.05). Conclusions: Cardiac ATTR amyloidosis is a cause of heart failure with pre- served EF that typically affects older men, but it does occur in women and younger patients. The clinical phenotype is rather non-specific, and although con- centric LV wall thickening and reduced longitudinal systolic function with moder- ate to severe diastolic dysfunction in association with elevated cardiac biomarkers are characteristic, the range of echocardiography findings was wide. Many recent referrals were prompted following CMR, which had strongly suggested amyloid in- filtration in most cases. These observations, coupled with the promise of specific new therapies in the near future, encourage a high index of suspicion for cardiac ATTR amyloidosis among older patients with heart failure and preserved EF. P5710 | BEDSIDE Effects of everolimus conversion from mycophenolate mofetil on cardiac allograft vasculopathy in heart transplant recipients T. Watanabe, Y. Murata, M. Hieda, H. Sunami, K. Nishimura, Y.Miyamoto, T. Sato, O. Seguchi, M. Yanase, T. Nakatani. National Cerebral and Cardiovascular Center Hospital, Department of Transplantation, Suita, Osaka, Japan Background: Use of EVL may reduce the progression of cardiac allograft vascu- lopathy (CAV) in primary HTx recipients. Our basic immunosuppression protocol is triple therapy with a calcineurin inhibitor (CNI; ciclosporin or tacrolimus), my- cophenolate mofetil (MMF), and prednisolone (PSL). In HTx recipients with CAV progression and/or renal dysfunction, we generally convert from MMF to EVL and reduce CNI administration. However, the efficacy of EVL for CAV is unknown. Purpose: We investigated the effects of everolimus (EVL) for vessel remodel- ing in maintenance heart transplant (HTx) recipients in regard to vessel volume changes, and lumen and plaque volumes. Methods: Seventy-two patietns who underwent heart transplantation from July 1997 to December 2012 at our institution were followed, of whom 15 were con- verted to EVL from MMF after a mean 2.4 years. Those patients underwent se- rial 3-dimensional intravascular ultrasound analysis of the first 50 mm of the left anterior descending coronary artery before EVL conversion and again after 12 months. As a control group, 30 patients matched for baseline year and who re- ceived our basic immunosuppression therapy were compared in regard to vessel volume changes, and lumen and plaque volumes. Results: The mean baseline maximal intimal thickness (MIT) and baseline plaque volume in the EVL group were significantly greater than in the control group (1.29±0.45 vs 0.71±0.45 mm, 137.70±74.12 vs. 59.42±43.43 mm 3 ,p<0.05). CAV progression was significantly suppressed in the EVL group as compared with the control group [maximal intimal thickness -0.11±0.32 vs. 0.07±0.24 mm (p=0.05), plaque volume -13.41±41.38 vs. 9.43±28.10 mm 3 (p=0.06)]. The EVL group also had kept lumen volumes and suppressed the progression of max stenosis rate (lumen volume 8.78±52.13 vs. -32.04±80.15 mm 3 , max steno- sis rate -5.65±8.95% vs 1.75±7.66%, p<0.05). Conclusion: Conversion to EVL from MMF suppressed CAV progression and reduced the degree of luminal narrowing in HTx recipients. P5711 | BEDSIDE Ischemia-modified albumin levels in patients with acute decompensated heart failure treated with dobutamine or levosimendan: IMA-HF study Y. Cavusoglu 1 , S. Korkmaz 2 , S. Demirtas 2 , E. Gencer 3 , H. Sasmaz 4 , F. Mutlu 1 , M.B. Yilmaz 5 on behalf of IMA-HF investigators. 1 Eskisehir Osmangazi University, Eskisehir, Turkey; 2 Ufuk University, Faculty of Medicine, Ankara, Turkey; 3 Kilis State Hospital, Department of Cardiology, Kilis, Turkey; 4 Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey; 5 Cumhuriyet University, Department of Cardiology, Sivas, Turkey Purpose: Ischemia-modified albumin (IMA) is a very sensitive biomarker of my- ocardial ischemia before necrosis. However, data about IMA levels specifically in patients with heart failure (HF) are still lacking. Dobutamine (DOB) is known to in- crease myocardial oxygen consumption, and thereby may precipitate myocardial ischemia and myocyte damage. In contrast to DOB, levosimendan (LEVO) does not increase myocardial oxygen demand and therefore is thought to have cardio protective properties. So, we aimed to evaluate 1-) serum IMA concentrations in acute decompensated HF and 2-) the effects of DOB and LEVO treatments on IMA levels. Methods: This prospective multicenter study was performed at the five indepen- dent sites. Fifty-nine patients admitted to participating centers with NYHA III-IV acute decompensated HF and LVEF <35% were enrolled in this study. Blood samples for IMA measurements were obtained from all patients at baseline and 24 h after the initiation of HF therapy. 18 patients were treated with guidelines- recommended HF therapy with oxygen, diuretic, vasodilators (control group), 18 patients received an additional 24-h infusion of LEVO with a loading dose of 12 μg/kg over 10 min followed by a continuous infusion of 0.2 μg/kg/min (LEVO group) and 23 patients had DOB treatment with a continuous infusion of 10 μg/kg/min for 24-h in addition to optimal pharmacologic therapy (DOB group). A single serum specimen was also collected from 32 apparently healthy individ- uals. IMA concentrations were measured by albumin cobalt binding colorimetric assay and results were given as absorbance units (AU). Results: In patients with acute decompensated HF, mean serum concentration of IMA was found to be significantly higher than those of apparently healthy population (0.894±0.23 AU vs 0.379±0.08 AU, p <0.0001). Overall, IMA lev- els significantly decreased after 24-h of the initiation of appropriate HF therapy (0.894±0.23 AU and 0.832±0.18 AU, p <0.013). Furthermore, IMA levels were Downloaded from https://academic.oup.com/eurheartj/article-abstract/34/suppl_1/P5709/2863449 by guest on 28 May 2020