Study question When is the optimal timing of day 6 (D6) blastocyst transfer between the 6thday (P6)and the 7th(P7) day of progesterone administration in artificially prepared frozen-thawed embryo transfer(FET) cycle Summary answer When transferring D6 blastocysts in artificially prepared FET cycles, live birth rate tended to be higher in P6 group than in P7 group. What is known already Blastocyst transfer in FET cycles has increased due to several reasons including convenience for optimization of endometrial synchronization, improvement of laboratory techniques and preimplantation genetic testing. Meanwhile, D6 blastocyst which cryopreserved on day 6 after being developed to the full blastocyst stage, presented lower pregnancy outcomes in FET cycle than D5 blastocysts. However, there have been few studies on the optimal duration of progesterone administration when transferring D6 blastocysts. Study design, size, duration This was a retrospective cohort study including patients who underwent frozen-thawed blastocyst transfer in artificially prepared cycles from January 2000 to May 2020. Patients with D6 blastocyst transfer on the 6th day of progesterone administration were included in D6-P6 group, and patients with D6 blastocyst transfer on the 7th day of progesterone administration were included in D6-P7 group. Participants/materials, setting, methods Increasing dose of estradiol valerate was administered from the 3rd day of menstruation: 4 mg/day for the first four days, 6 mg/day for next four days, and then 8 mg/day until the confirmation of pregnancy. Progesterone was administered from the 14th day of menstruation if the endometrial thickness reached ≥7 mm. The independent t-test or Mann-Whitney test, chi-square test, and logistic regression analysis were performed. Main results and the role of chance A total of 50 patients were included, and 13 patients underwent FET on P6 and 37 patients underwent FET on P7. Live birth rate was comparable between the P6 group and the P7 group (18.9% vs. 15.4%, p = 0.775). Live birth rate was higher in the D6-P6 group than in the D6-P7 group after adjusting for age, AMH, endometrial thickness on the starting day of progesterone administration and good embryo rate transferred with statistical significance (OR: 6.716, p = 0.005). Limitations, reasons for caution Limitations of the present study is the retrospective design and the small sample size. Caution is needed in extrapolating results of this study because only intramural and vaginal progesterone supplementations were included in this study. Wider implications of the findings: Even if the duration of blastocyst formation was delayed, frozen-thawed D6 blastocyst may need to be considered for on P6 rather than P7. The difference of live birth rate is not statistically significant. This study should be acknowledged for the underestimation of the difference because of the small sample size. Trial registration number Not applicable

Background It is unclear whether and how diabetes mellitus may aggravate myocardial fibrosis and remodeling in the pressure-overloaded heart. We investigated the impact of diabetes on the prognosis of aortic stenosis (AS) patients and its underlying mechanisms using comprehensive noninvasive imaging studies and plasma proteomics. Methods Severe AS patients undergoing both echocardiography and cardiovascular magnetic resonance (CMR) (n=253 of which 66 had diabetes) comprised the imaging cohort. The degree of replacement and diffuse interstitial fibrosis by late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) was quantified using CMR. Plasma samples were analyzed with the multiplex proximity extension assay for 92 proteomic biomarkers in a separate biomarker cohort of severe AS patients (n=100 of which 27 had diabetes). Results In the imaging cohort, diabetic patients were older (70.4±6.8 vs. 66.7±10.1 years) and had a higher prevalence of ischemic heart disease (28.8% vs. 9.1%), with more advanced ventricular diastolic dysfunction. On CMR, diabetic patients had increased replacement and diffuse interstitial fibrosis (LGE% 0.3 [0.0–1.6] versus 0.0 [0.0–0.5], p=0.009; ECV% 27.9 [25.7–30.1] versus 26.7 [24.9–28.5], p=0.025) (Figure 1). Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) are significantly elevated in diabetic AS patients (Figure 2). Pathway over-representation analyses of the plasma proteomics with Gene Ontology terms indicated that pathways related to inflammatory response and extracellular matrix components were enriched, suggesting that diabetes is associated with systemic effects that evoke proinflammatory and profibrotic response to the pressure-overloaded myocardium. During follow-up (median 6.3 years [IQR 5.2–7.2]) of the imaging cohort, 232 patients received aortic valve replacement (AVR) with 53 unexpected heart failure admissions or death. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and AVR (hazard ratio 1.88, 95% confidence interval 1.06–3.31, p=0.030). Conclusion Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory and profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea

Background Aortic stenosis (AS) induces significant pressure overload to the left ventricle (LV) and its burden may increase if there is concomitant LV systolic dysfunction. Severe AS with LV systolic dysfunction is a class I indication for aortic valve replacement (AVR) irrespective of symptoms, however, this recommendation is not well established in those with moderate AS and LV systolic dysfunction. In this study, we sought to investigate the clinical impact of surgical AVR among patients with moderate AS and LV systolic dysfunction. Methods From 2001 to 2017, we retrospectively but consecutively identified patients with moderate AS and LV systolic dysfunction from a single tertiary hospital. Moderate AS was defined as aortic valve area between 1.0 and 1.5cm2 and LV systolic dysfunction as LV ejection fraction less than 50%. The primary outcome was all-cause death and we additionally analyzed cardiac death as a secondary endpoint. The outcomes were compared between those who underwent early surgical AVR at the stage of moderate AS versus those who were followed without AVR at the outpatient clinic. Results Among a total of 257 patients with moderate AS and concomitant LV systolic dysfunction (70.0 ± 11.3 years, 63.4% of male), 34 patients received early AVR. Patients in the AVR group was younger than the observation group (64.2 ± 8.1 vs. 70.9 ± 11.5, respectively), and had a lower prevalence of hypertension and chronic kidney disease. During a mean of 3-year follow up, 112 patients (47.5%) died and the overall death rate was 15.367 per 100 person-year (PY). The AVR group showed a significantly lower rate of all-cause death than the observation group (5.241PY vs. 18.160PY, p-value = 0.002). After multivariable Cox proportional hazard regression adjusting for age, sex, comorbidities and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of all-cause death (hazard ratio [HR] 0.340, 95% confidence interval [CI] 0.117 - 0.985, p-value = 0.047). However, there was no risk reduction of cardiac death (HR 0.578 95% CI 0.150 - 2.231, p-value = 0.426). Conclusions In patients with moderate AS and LV systolic dysfunction, AVR reduces the risk of all-cause death. A prospective design study is warranted to confirm our findings in the near future. Abstract P1274 Figure. Kaplan-Meier curves for deaths

Funding Acknowledgements This study was supported by grants from Boryung Pharmacy Research Fund. Background/Introduction: Pathophysiology of aortic stenosis (AS) and several previous studies suggested the potential role of angiotensin receptor blocker (ARB) in patients with AS. Purpose We aimed to investigate the effects of Fimasartan, an ARB, on exercise capacity and progression of AS in patients with moderate to severe AS. Methods We conducted a prospective, randomized, double-blind, placebo-controlled trial in 32 normotensive or controlled-hypertensive patients with moderate or severe AS. Study participants were randomized to Fimasartan 30 mg to 60 mg daily (n = 14) or placebo (n = 18) for 1 year, and underwent cardiopulmonary exercise test, 6-minute walk test, and echocardiography at 0, 6, and 12 months, with follow-up data available in 29 subjects. Results Significant reductions in blood pressures were observed in the Fimasartan group but not in the placebo group. Two of the 14 patients in the Fimasartan group withdrew the study due to mild symptoms probably related with the decreased blood pressure, and one patient decline the study protocol. After the 12-month treatment, the peak oxygen consumption (VO2; the primary outcome) in the Fimasartan group was significantly decreased (from 28.3 ± 5.9 to 25.4 ± 3.8 mL/min/kg, P = 0.021) but not in the placebo group (P for interaction = 0.046) (Figure 1A). The severity of AS showed a gradual progression in both groups, without inter-group differences (mean transaortic pressure; Fimasartan group, +4.0 ± 3.8 mmHg/year; placebo group, +5.3 ± 6.2 mmHg/year; P for interaction = 0.429) (Figure 1B). Parameters of left ventricular systolic and diastolic function did not change in both groups. Conclusions The use of ARB impaired exercise capacity in patients with moderate or severe AS, and did not prevent the progression of AS. However, due to the small number of participants, further studies are required to confirm these findings. Abstract P1368 Figure.

Funding Acknowledgements This study was supported by the grant of CJ healthcare 2016 research fund. Background Liver cirrhosis (LC) has been known to affect cardiovascular performance. Limited study have evaluated the alteration of myocardial function in patients with LC after liver transplantation (LT). Purpose The aim of study was to evaluate changes of cardiac function in patients with cirrhosis following LT using conventional and speckle-tracking echocardiography and late gadolinium enhancement (LGE) of cardiac magnetic resonance (MR). Methods Thirty-five patients with cirrhosis (mean age, 57.1 ± 9.0; male, 75%) who were listed for LT were prospectively enrolled. Patients underwent conventional, speckle-tracking echocardiography, and cardiac MR imaging with LGE. Echocardiography and cardiac MR were performed at pre and 1 year after LT. Cirrhotic patients were compared with normal control (n = 20, mean age, 65.0 ± 14.8; men, 11(55%)) and echocardiographic and cardiac MR data were compared pre and post LT. Results Conventional and speckle-tracking echocardiography and Cardiac MR imaging demonstrated hyperdynamic left ventricular (LV) function in patients with cirrhosis (LV ejection fraction (EF) with cardiac MR 67.8 ± 7.0% in LC vs. 63.4 ± 6.4% in control, P = 0.028; global longitudinal strain (GLS) -24.3 ± 2.6% in LC vs. -18.6 ± 2.2% in control, P < 0.001). There were no LGE in patients with cirrhosis and no significant differences in LV size, LV wall thickness, LV mass index, and diastolic function between cirrhotic patients and control group (all P > 0.1). Corrected QT interval (QTc) in electrocardiogram was prolonged in LC patients (P < 0.001). One-year after LT, LV end-diastolic diameter and LV end-diastolic volume significantly decreased (P = 0.016 and 0.022, respectively). Although LVEF showed no significant changes 1 year post-LT (P = 0.362), LV-GLS (from -24.7 ± 1.8% to -20.8 ± 3.4%, P < 0.001) significantly decreased. QTc interval also decreased 1 year after LT (from 470.4 ± 29.6msec to 428.2 ± 31.6msec, P = 0.001). Conclusions The present study demonstrated that cirrhotic patients showed hyperdynamic circulation and prolonged QTc interval compared with normal controls. After 1 year LT, LV size reduced and augmented LV function was normalized. Given that no LGE in cardiac MR and normalized GLS and QTc after LT, cardiac dysfunction in LC patients could be reversed by LT.