Background Ischemic stroke is a common complication in patients with hypertrophic cardiomyopathy (HCM) (1). Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke in HCM, the risk of ischemic stroke in patients with HCM without documented AF is less recognized (1, 2). This study aimed to determine the risk of ischemic stroke and identify its risk factors in patients with HCM without documented AF. Methods This nationwide population-based cohort study used the Korean National Health Insurance database. After excluding patients with a prior history of AF, thromboembolic events, cancer, or the use of anticoagulants, we identified 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls. The clinical outcome was an incident ischemic stroke. Results During a mean follow-up of approximately 6 years, ischemic stroke occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. Among individuals who developed ischemic stroke, the proportion of AF concomitantly detected accounted for 26.5% (87/328) and 5.8% (26/443) in the HCM and control groups, respectively. The overall incidence of ischemic stroke was 0.716/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.643; 95% CI, 1.424–1.895; P<0.001, Figure 1). The subgroup analysis according to age, sex, and comorbidities (chronic heart failure, hypertension, dyslipidemia, and vascular disease) consistently demonstrated a higher risk of ischemic stroke in the HCM group (P for interaction >0.05). In the HCM group, age ≥65 years (adjusted hazard ratio [HR] 2.741; 95% confidence interval [CI], 2.156–3.486; P<0.001) and chronic heart failure (adjusted HR 1.748; 95% CI, 1.101–2.745; P=0.018) were independent risk factors for ischemic stroke. Overall incidence was 1.360/100 in patients with HCM aged ≥65 and 2.315/100 person-years years in those with chronic heart failure, respectively. Also, compared to controls aged <65 years and without CHF, adjusted HR for ischemic stroke was 4.756 (95% CI 3.807–5.867) in patients with HCM aged ≥65 years and 2.539 (95% CI 1.638–3.936) in those with CHF, respectively (Figure 2). Conclusions Patients with HCM without documented AF are at a higher risk of ischemic stroke than the propensity score-matched general population. Age ≥65 years and chronic heart failure are two strong independent risk factors for ischemic stroke in this population. Funding Acknowledgement Type of funding sources: None.

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

Funding Acknowledgements N/A Background/Introduction: The benefit of statins in patients with heart failure (HF) remains controversial and the mechanism of action is largely speculative. We investigated whether survival benefit with statins differs according to left ventricular (LV) geometry and myocardial contractility in acute HF patients. Methods We enrolled 1792 acute HF patients receiving statins and 2296 patients not receiving statins admitted from 2009 to 2016. The LV and right ventricular (RV) global longitudinal strain (GLS) was assessed as a measure of myocardial contractility. Patients were classified into 2 groups based on ischemic etiology of HF and further divided into 4 subgroups according to the median values of LV-GLS or RV-GLS. The primary outcome was 5-year all-cause mortality. The study protocol was approved by the ethics committee at each institute and complied with the Declaration of Helsinki. The need for written informed consent was waived. Results During the 5-year follow-up, 1740 (40.4%) patients died and they had more unfavorable baseline characteristics. Statin therapy was significantly associated with improved survival in overall patients and in both groups with and without ischemic etiology (all p <0.001). Patients with concentric remodeling/hypertrophy and eccentric hypertrophy demonstrated survival benefit with statin therapy (P = 0.033, 0.004, and 0.008, respectively), while those with normal geometry did not (p = 0.123). In the non-ischemic HF group, survival benefit with statin therapy was confined to patients with low LV-GLS (p = 0.045) or those with low RV-GLS p = 0.003). On the contrary, in ischemic HF group, survival benefit with statin therapy was observed in all patients regardless of the values of LV-GLS or RV-GLS. Significant interactions were present between statin use and diabetes mellitus and IHD (p for interaction = 0.027 and 0.003, respectively) regarding mortality. Conclusions LV geometry and myocardial contractility may modulate the effects of statins in patients with acute HF. These echocardiographic measures can provide prognostic information to guide tailored statin treatment in this population. Our findings may also help to develop more well-designed prospective studies, in terms of a more homogenous study population, to confirm survival benefit with statin therapy. Abstract P785 Figure. Multivariate Cox survival curves

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

Purpose A number of risk prediction models have been developed to identify short term mortality after cardiovascular surgery. Most models include patient characteristics, laboratory data, and type of surgery, but no consideration for the amount of surgical experience. With numerous reports on the impact of case volume on patient outcome after high risk procedures, we attempted to develop a risk prediction models for in-hospital and 1-year mortality that takes institutional case volume into account. Methods We identified adult patients who underwent cardiac surgery from January 2008 to December 2017 from the National Health Insurance Service (NHIS) database by searching for patients with procedure codes of coronary artery bypass grafting, valve surgery, and surgery on thoracic aorta during the hospitalization. Study subjects were randomly assigned to either the derivation cohort or the validation cohort. In-hospital mortality and 1-year mortality data were collected using the NHIS database. Risk prediction models were developed from the derivation cohort using Cox proportional hazards regression. The prediction performances of models were evaluated in the validation cohort. Results The models developed in this study demonstrated fair discrimination for derivation cohort (N=22,004, c-statistics, 0.75 for in-hospital mortality; 0.73 for 1-year mortality) and acceptable calibration in the validation cohort. (N=22,003, Hosmer-Lemeshow χ2-test, P=0.08 and 0.16, respectively). Case volume was the key factor of mortality prediction models after cardiac surgery. (50≤ x <100 case per year. 100≤ x <200 case per year, ≥200 case per year are correlated with OR 3.29, 2.49, 1.85 in in-hospital mortality, 2.76, 1.99, 1.69 in 1-year mortality respectively, P value <0.001.) Annual case volume as risk factor Variables In-hospital mortality 1-year mortality OR (95% CI) p-value OR (95% CI) p-value Annual case-volume (reference: ≥200) – – 100–200 1.69 (1.48, 1.93) <0.001 1.85 (1.58, 2.18) <0.001 50–100 1.99 (1.75, 2.25) <0.001 2.49 (2.15, 2.89) <0.001 <50 2.76 (2.44, 3.11) <0.001 3.29 (2.85, 3.79) <0.001 OR: Odds ratio; CI: confidence interval; Ref: Reference. Discrimination and calibration Conclusion We developed and validated new risk prediction models for in-hospital and 1-year mortality after cardiac surgery using the NHIS database. These models may provide useful guides to predict mortality risks of patients with basic information and without laboratory findings.