Abstract 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
Abstract 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
Abstract 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.
Abstract Background An elective switching to the subcutaneous (SC) formulation of infliximab (IFX) has shown effectiveness and safety in patients with inflammatory bowel disease (IBD) on intravenous (IV) IFX maintenance therapy. However, data on long-term outcomes in patients not in clinical remission during maintenance therapy is limited. This study aims to evaluate the long-term outcomes of SC switching in patients who were in clinical remission and not in remission during IV IFX maintenance therapy. Methods This retrospective multicentre study was conducted from January 2021 to October 2023. Clinical remission was defined as Crohn’s Disease Activity Index (CDAI) <150 for Crohn’s disease (CD) and partial Mayo score <2 for ulcerative colitis. Biological remission was defined as faecal calprotectin (FC) <250 µg/g and C-reactive protein (CRP) <0.5 mg/dL. The primary outcome measure was 1-year treatment persistence of SC IFX. Results Among 127 patients included in the study, 80 (62.9%) had CD, and 47 (37.1%) had UC. At the time of switching, 90 patients (70.9 %) were in clinical remission; whereas, 37 (29.1 %) were in a non-remission state. The treatment persistence rate at 1 year was high at 92.9%. Treatment persistence rates between the clinical remission and non-remission groups did not differ significantly (94.4% vs. 89.2%, p=0.287). In both groups, IFX pharmacokinetics and biomarkers between baseline and 12 months (p<0.01) significantly improved. The median infliximab levels increased from a baseline of 3.3 µg/mL (interquartile range [IQR] 1.3–5.1) to 14.4 µg/mL (IQR 9.4–23.0, p<0.001) at 12 months. Disease activity index was stable in the remission group, and decreased in the non-remission group (partial Mayo score, p<0.001; CDAI, p=0.063). At the one-year follow-up, clinical remission and biological remission were achieved in 86.6% and 60.6%, respectively, an increase from baseline (70.9% and 48.0%, respectively). Biologics exposure before IFX was the only significant variable associated with treatment persistence (odds ratio 5.138, 95% confidence interval 1.150–22.951, p=0.032). The concomitant use of immunomodulators was not associated. The incidence of IFX-related adverse events was 14.2%, with only three patients discontinuing treatment. Conclusion Switching to SC IFX from IV IFX maintenance therapy demonstrated high treatment persistence and favourable safety profiles, irrespective of remission status at the time of switching. Patients in both remission or non-remission states showed significant improvement in pharmacokinetics and biomarkers, and/or stable disease activity indices.
Abstract Background Despite an overall decrease in cardiovascular mortality in recent decades due to effective preventive strategies, a concerning trend is emerging among young adults, with a rising incidence of myocardial infarction (MI) and its poor prognosis. Previous studies report that a significant association between mental disorders and the incidence and prognosis of MI. However, a detailed age-specific information is still lacking. Purpose We aimed to determine whether the risk of developing mental disorders after MI differs based on age and to stratify individuals at a higher risk. Methods From the UK Biobank prospective database (n=502,386), we collected data on patients with a prior MI (n=10,840) and compared them to age- and sex-matched controls (n=54,197) in a 1:5 ratio. Diagnoses of mental disorders were ascertained through linked hospital admission and mortality data, using the appropriate ICD-10-CM codes. Mental disorders were defined by at least two inpatient or outpatient claims within 1 year. The primary outcome was a composite of incident mental disorders, including depression, anxiety, stress-related, and somatoform disorders. Follow-up was done until the first diagnosis of mental disorders or the end of 2022. Results During a median follow-up of 13.7 years (interquartile range 12.8-14.5 years), the incidence rate of the primary outcome was 9.28 vs. 5.37/1,000 person-years among patients with MI and controls, respectively (p<0.001). A prior MI history demonstrated an independent association with the risk of incident mental disorders, yielding an adjusted hazard ratio (aHR) of 1.41 (95% confidence interval [CI], 1.29–1.54; p<0.001) after adjusting for confounders. This was comparable to heavy drinking and family history of depression. Notably, the risk of mental disorders attributed to previous MI was more prominent in younger individuals aged <55 years than their older counterpart (aHR 1.61 vs. 1.33) (p-for-interaction 0.020). Similar results were observed in the analysis of two important components: depression and anxiety disorder. Furthermore, in younger patients with MI (<55 years), mental disorders significantly increased the risk of mortality, while not in older patients. Conclusion MI was associated with a higher risk of incident mental disorders, resulting in poor prognosis, particularly in young individuals. Active surveillance and prevention for incident mental disorders after young MI may be beneficial.Cumulative Incidence of Mental Disorders
Abstract 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.
Abstract 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.
Abstract Background Atrial fibrillation (AF) is increasingly recognized as a cause of tricuspid regurgitation (TR) in the structurally normal tricuspid valve. However, there are limited data regarding the impact of AF on TR progression and its long-term cardiovascular outcomes. Purpose We aimed to investigate the association of AF with the significant TR progression and its impact on clinical outcomes among patients with isolated mild functional TR. Methods We studied 834 patients with mild function TR identified on the echocardiography between 2007 and 2019, whose follow-up echocardiography beyond 1-year was available. Major exclusion criteria were the overt causes of primary and secondary TR (i.e., concomitant left-sided heart disease). Primary endpoint was the significant TR progression to more than a moderate degree on the follow-up echocardiography. Composite cardiac event was defined as cardiovascular death, TR surgery, and heart failure admission due to TR. Results Of 834 patients with isolated mild functional TR (mean age 65.6 years, 41% men), 292 (35.0%) patients had AF at the baseline. Patients with AF were older and had larger left atrium compared to those without. During the median of 4.55 years follow-up (interquartile interval 2.56–7.24 years), 36 patients developed a significant TR ≥ moderate degree. The cumulative rate of TR progression was significantly higher in patients with AF than those without (11.3% versus 0.6%, P<0.001) (Figure 1). Multivariable Cox analyses showed that AF was associated with a 3-fold higher risk of TR progression (adjusted hazard ratio 3.50, 95% confidence interval 1.42–8.65). Regarding the cardiovascular outcomes, patients who developed significant TR had a higher rate of composite cardiac events compared to those who did not (cardiac events: 38.9% versus 6.3% P<0.001) (Figure 2). Conclusions AF is a strong risk factor for TR progression among patients with isolated mild functional TR. In addition, the development of significant TR is associated with worse cardiovascular outcomes. These findings highlight the important pathophysiology of AF on TR development and its clinical consequences. Funding Acknowledgement Type of funding sources: None.
Abstract 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
Abstract 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.
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