Asian Patients Research Articles

Optimal Diagnostic and Treatment Response Threshold of the Eosinophilic Esophagitis Endoscopic Reference Score: A Single-Center Study of 102 Patients With Eosinophilic Esophagitis.

The proposed eosinophilic esophagitis (EoE) endoscopic reference score serves to diagnose and evaluate treatment responses in EoE. Nevertheless, the validated reference score thresholds for diagnosis and treatment response in Asian patients are yet to be established. This study aims to establish these thresholds for the first time among Asian patients with EoE. Patients presenting with ≥ 15 eosinophils/high power field and esophageal dysfunction symptoms between August 2007 and November 2021 were included. Age- and sex-matched non-EoE controls were also enrolled. Baseline characteristics, endoscopic reference score features, and scores were compared between patients and controls. Among patients, endoscopic reference score features and scores, along with peak eosinophil counts, were evaluated both before and after treatment. The optimal threshold was determined based on sensitivity, specificity, and the Youden index. Overall, 102 patients were enrolled (74.5% men; mean age, 46.9 years). The mean endoscopic reference score was 2.65 and 0.52 for patients and controls, respectively (P < 0.001). An endoscopic reference score ≥ 2 was identified as the optimal diagnostic threshold for EoE (sensitivity, 0.79; specificity, 0.86; Youden index, 0.66). Post-treatment data regarding endoscopic findings and histology were available for 30 patients. Regarding histologic response, an endoscopic reference score of ≤ 3 demonstrated the optimal threshold (sensitivity, 0.95; specificity, 0.88; Youden index, 0.83). The optimal diagnostic and treatment response thresholds were determined to be endoscopic reference scores of ≥ 2 and ≤ 3, respectively. Further studies involving a larger patient cohort are necessary to validate these findings.

Clinical validation of peripheral blood mononuclear cell DNA methylation markers for accurate early detection of hepatocellular carcinoma in Asian patients

BackgroundHepatocellular carcinoma (HCC), a leading cause of cancer-related deaths globally, poses significant challenges in early detection. Improved diagnostic accuracy can drastically influence patient outcomes, emphasizing the need for innovative, non-invasive biomarkers.Methods:This study utilized a cohort of 402 participants, including healthy controls, chronic hepatitis patients, and HCC patients from Bangladesh, to evaluate DNA methylation signatures in peripheral blood mononuclear cells (PBMC). We performed targeted next-generation sequencing on selected genes previously identified to assess their methylation dynamics. The development of M8 and M4 scores was based on these dynamics, using Receiver Operating Characteristic (ROC) analysis to determine their effectiveness in detecting early-stage HCC alongside existing markers such as epiLiver and alpha-fetoprotein (AFP).Results:Integration of M8 and M4 scores with epiLiver and AFP significantly enhances diagnostic sensitivity for early-stage HCC. The M4+epiLiver score achieves a sensitivity of 79.4% in Stage A HCC, while combining M4 with AFP increases sensitivity to 88.2–95.7% across all stages, indicating a superior diagnostic performance compared to each marker used alone.Conclusions:Our study confirms that combining gene methylation profiles with established diagnostic markers substantially improves the sensitivity of detecting early-stage HCC. This integrated diagnostic approach holds promise for advancing non-invasive cancer diagnostics, potentially leading to earlier treatment interventions and improved survival rates for high-risk patients.

Determinants of quality of life and emotional well-being in a bariatric surgery seeking cohort of 1501 multi-ethnic Asian patients.

The relationship between ethnicity, obesity and health-related quality of life outcomes in a multi-ethnic population remains poorly understood. We aim to investigate the relationship between ethnicity, body mass index (BMI), obesity-associated diseases, as well as determinants of quality of life (QoL) in Southeast Asian patients with obesity. We aim to develop and validate a simple objective score to identify patients with obesity at high risk for major depression. Associations between ethnicity, obesity-associated diseases, BMI and determinants of QoL (Patient Health Questionnaire-9 and 36-Item Short Form Survey) were analysed using multivariate logistic regression in a prospective cohort of 1501 patients with obesity. Multivariate regression and receiver operating characteristics curves were used to develop and validate a novel scoring system to identify patients at risk of major depression. Patients of Chinese, Malay and Indian ethnicity had increased risk of hypertension (odds ratio [OR]: 1.51 [95% confidence interval [CI]: 1.19-1.92, p < .001]), BMI Class 4 (OR: 17.89 [95% CI: 9.53-33.60, p < .001]) and major depression (OR: 1.71 [95% CI: 1.23-2.39, p = .002]), respectively. Factors associated with major depression (gender, ethnicity, age, obstructive sleep apnoea, Physical Component Score and Mental Component Score scores) were used to create and validate a novel scoring system with an area under curve of 0.812 (95% CI: 0.787-0.837). A cutoff of 4 of 7 points was identified with a sensitivity of 70%, specificity of 81%, positive predictive of 53% and negative predictive value of 90%. The prevalence of metabolic complications from obesity significantly varies with ethnicity. We developed a novel and simple scoring tool combining objective demographic and patient-reported outcomes to screen and triage patients at risk of major depression.

New evidence on patella resurfacing in modern total knee arthroplasty for all inflammatory arthritis in a mixed Asian population

BackgroundTraditional teaching advocates for routine patella resurfacing (PR) during total knee arthroplasty (TKA) in patients with inflammatory arthritis. However, evidence on this topic remains limited in the Asian population. This study aims to evaluate the postoperative outcomes and complication of patella resurfacing (PR) during primary total knee arthroplasty (TKA) in Asian patients with inflammatory arthritis. MethodsA retrospective analysis was conducted using registry data from our institution. Patients with inflammatory arthritis who underwent primary TKA from August 2017 to December 2021 were included in the study. Patients were divided into two groups - patella resurfaced (PR, n = 25) and non-resurfaced patella (PNR, n = 31) groups. Demographics, operative data, patient reported outcome measures, and complications were compared. ResultsPreoperative range of motion (ROM) (PR:95.3 ± 23.6° vs PNR:105 ± 19.5°, p = 0.106), Knee Society Scoring System Knee score (KS-KS) (PR:44.6 ± 17.4 vs PNR:49.3 ± 17.7, p = 0.331) and Knee Society Function Score (KS-FS) (PR:40.9 ± 27.3 vs PNR:47.7 ± 27.0, p = 0.325) and Oxford Knee Score (OKS) (PR:25.0 ± 7.8 vs PNR:23.3 ± 10.3, p = 0.525) were similar in both groups. Outcomes between PR and PNR groups at the one-year mark in terms of ROM (PR:112.7 ± 18.1 vs PNR:114.6 ± 16.5, p = 0.455), OKS (PR:41.5 ± 3.9 vs PNR:41 ± 4.7, p = 0.954), KS-KS (PR:84.5 ± 13.2 vs PNR:89.2 ± 9.3, p = 0.095) and KS-FS (PR:73.6 ± 18.3 vs PNR:78.7 ± 19.3, p = 0.173) were also similar. Intraoperative complication (PR:0/25 vs PNR: 3/31 (9.6 %), p = 0.245) and re-operation rates (PR: 1/25 (4 %) vs PNR: 1/31 (3.2 %), p = 0.877) were also similar in both groups. ConclusionThis study conducted on a mixed Asian population with inflammatory arthritis demonstrated that the one-year postoperative ROM and functional outcomes, complication, and re-operation rates between PR and PNR groups were similar. Hence, routine patella resurfacing on all Asian patients with inflammatory arthritis undergoing TKA may not be necessary.

Polygenic risk score for drug-induced long QT syndrome: independent validation in a real-world patient cohort.

Drug-induced long QT syndrome (diLQTS) is an adverse reaction from over 150 FDA-approved medications, posing the risk of triggering torsades de pointes and sudden death. While common genetic variants may modestly impact QT interval individually, their collective effect can significantly amplify risk of diLQTS. Consequently, this study aimed to validate a polygenic risk score (PRS) for diLQTS previously proposed by Strauss et al. A retrospective cohort study was conducted utilizing patients from the Michigan Genomics Initiative prescribed 27 high-risk QT-prolonging drugs and an ECG during the prescription. The primary outcome was marked prolongation of the QTc interval (either >60 ms change from baseline or >500 ms absolute value) during treatment with a high-risk QT-prolonging drug. The primary outcome occurred in 12.0% of n = 6070 self-reported White, 12.4% of 558 African American, and 8.2% of 110 Asian patients. The PRS significantly associated with diLQTS in White patients [adjusted odds ratio = 1.44 (95% CI: 1.09-1.89); P = 0.009]. However the study lacked sufficient statistical power to confirm the PRS as a risk factor in African Americans [adjusted odds ratio = 2.18 (95% CI: 0.98-5.49); P = 0.073] and Asians [adjusted odds ratio = 3.21 (95% CI: 0.69-16.87); P = 0.139] due to smaller sample sizes in these groups. The previously published PRS for diLQTS was validated in a large, real-world cohort, demonstrating its potential as a tool for identifying high-risk patients. Incorporating this PRS into routine clinical practice could enable proactive measures to prevent life-threatening diLQTS.

Race in heart failure: a pooled participant-level analysis of the global PARADIGM-HF and PARAGON-HF trials

Abstract Background Mechanisms of disease pathobiology, prognosis, and potentially treatment responses might vary by race in patients with heart failure (HF). Early experiences with neprilysin inhibition suggested possible increased risks of angioedema, especially among Black individuals. We aimed to examine the safety and efficacy profile of sacubitril/valsartan in a pooled participant-level dataset of 2 large cohorts of patients with HF by self-reported race. Methods PARADIGM-HF and PARAGON-HF were multicenter, randomized clinical trials testing sacubitril/valsartan against a renin-angiotensin system inhibitor (RASi, enalapril or valsartan, respectively) in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF). We included all patients with available data on self-reported race and categorized patients as White, Asian, or Black. We assessed adjudicated outcomes including the composite of first HF hospitalization (HFH) or cardiovascular (CV) death, its components, and angioedema by racial group. Results Among 12,097 included participants, 9,451 (78.1%) were White, 2,116 (17.5%) were Asian, and 530 (4.4%) were Black. Asian participants were from 19 countries, with highest enrollment from India, China, and the Philippines. Black participants were from 18 countries, with highest enrollment from the US, South Africa, and Brazil. Black patients had the worst baseline health status (adjusted KCCQ-OSS mean 70.3), while White (71.4) and Asian patients (76.4) had better health status; P&amp;lt;0.001. Over 2.4-years of median follow-up, Black (adjusted HR 1.67; 95% CI 1.37-1.89; P&amp;lt;0.001) and Asian patients (adjusted HR 1.32; 95% CI 1.16-1.50; P&amp;lt;0.001) experienced higher risks of the primary outcome compared with White patients (Figure 1). The treatment effects of sacubitril/valsartan vs. RASi on the primary endpoint were consistent among White (HR 0.84; 95% CI: 0.77-0.91), Asian (HR 0.92; 95% CI: 0.78-1.10), and Black patients (HR 0.79; 95% CI: 0.58-1.07; Pinteraction = 0.39). In light of higher baseline risks, Black patients accrued the greatest absolute risk reduction with sacubitril/valsartan (Figure 2). Consistent treatment benefits by race were also observed for the individual components (CV death alone and first HFH alone). Rates of any adjudicated angioedema were numerically higher with sacubitril/valsartan vs. RASi across race groups (White 0.4% vs. 0.2%; Asian 0.6% vs. 0.2%; Black 2.3% vs. 0.8%), however no patient in either trial experienced airway compromise or required mechanical airway protection. Conclusions In a pooled experience of over 12,000 participants enrolled in 2 trials conducted across 56 countries, Black and Asian patients exhibited a higher risk of CV events than White patients. Rates of non-serious angioedema were numerically higher with sacubitril/valsartan across race groups. The relative CV benefits of sacubitril/valsartan were consistent across races, with greatest absolute benefits observed in Black patients.

Assessment of quality of life and ICD shock-related anxiety in Asian patients with implantable cardioverter defibrillator in the PainFree SST study

Abstract Background The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, it is not known if the psychological status of ICD patients differs by geography. The aim of this analysis is to compare Quality of Life (QoL) and ICD shock-related anxiety between ICD patients in Asian with those in other countries. Methods The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). The EuroQol 5-D (EQ-5D) measured QoL and the Florida Shock Anxiety Scale (FSAS) measured ICD shock-related anxiety. These questionnaires were administered bi-annually and monthly for 6 months after a shock. Change in QoL and shock anxiety was analyzed used linear mixed models for repeated measures. Results: Both the EQ-5D health score and FSAS score were higher in Asian patients compared to patients in the other countries post-implant (EQ-5D: 69.5 ± 18.3 points vs 66.5 ± 19.3 points, p&amp;lt;0.0001, FSAS: 19.7 ± 9.4 points vs 16.4 ± 7.7 points, p&amp;lt;0.0001), and stayed higher for the entire follow-up period (Figure 1). The EQ-5D health score was significantly reduced after a shock (Asian: -18.1 points, p&amp;lt;0.0001; other countries: -7.5 points, p&amp;lt;0.0001) with a greater reduction in Asian patients (p=0.0035) . Recovery in the month following a shock was greater in Asian patients (+19.8 vs +3.6 points, p&amp;lt;0.0001). The FSAS score was significantly increased after a shock (Asian: +6.4 points, p&amp;lt;0.0001; other countries: +4.8 points, p&amp;lt;0.0001) and the increase was similar between geographies (p=0.20). The recovery effect at 1 month was greater in Asian patients (-5.8 vs -1.7 points, p=0.0003) (Figure 2). Conclusions Asian patients were more anxious about a shock in spite of greater QoL, compared with those in other countries. After a shock, Asian patients had a greater decrease in QoL and a similar increase in anxiety but recovery was greater in both measures in the month following a shock.Figure 1Figure 2

Defibrillator shocks and their effect on objective asian patient outcomes: results of the painfree SST clinical trial

Abstract Background The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, the effect of ICD shock on device-measured activity is unknown. The aim of this analysis was to analyze the acute and long-term effects of ICD shock on objective behavioral data. Methods The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). Patient physical activity was determined from the device built-in accelerometer. The device translates the accelerometer output into a count of active minutes, which is stored as a daily total value in device memory for a rolling window of 425 days. Obviously, activity is measured only after device implantation. Early after implant, activity is reduced due to the procedure and thus not representative. Therefore, no baseline can be reported for activity. The follow-up activity data was analyzed with a linear mixed model, with a random effect for patient and an auto-regressive correlation matrix for subsequent measurements of individual patients. Results Figure 1 shows average daily activity between 90 days before and 90 days after a shock. The dashed vertical line indicates the day of shock. Both patients from Asia and from other countries show a drop in activity after a shock with recovery in the subsequent 30-60 days. The curve for Asian patients is more variable than the curve for other countries due to the lower number of patients (there were 33 Asian patients with shocks contributing data). Figure 2 shows average daily activity before and after ATP therapy. Any post shock measurement is excluded. Contrary to the temporary reduction in activity around a shock (Figure 1), ATP therapies do not seem to have an impact on activity. In patients from the other countries, activity is significantly reduced when patients are hospitalized (-66.3 minutes/day, p&amp;lt;0.0001), but not in Asian patients (-5.1 minutes/day, p=0.71). Both in Asian and other countries, activity is significantly reduced after an ICD shock (Asian: -47.5 minutes/day, p=0.0002; Other countries: -21.5 minutes/day, p&amp;lt;0.0001). The effect of shock for Asian is greater than the other countries (p=0.054). In the month after the shock there is a significant recovery, +34.8 minutes/day in Asian patients (p=0.0077) and +7.7 minutes/day in patients from other countries (p=0.031). The recovery is trended to be bigger in Asian patients (p=0.058). Conclusions ICD shocks have a lasting adverse impact on objective, device-measured physical activity, particularly among Asian individuals. Successful management of patients with an ICD necessitates specific attention to clinically relevant behavioral outcomes, aiming to expedite recovery and facilitate a return to activities of daily living, with a particular focus on the Asian population.

Peripheral artery disease, antithrombotic treatment and outcomes in European and Asian patients with atrial aibrillation: a report from 2 prospective observational registries

Abstract Background In patients with atrial fibrillation (AF), the impact of peripheral artery disease (PAD) on oral anticoagulant (OAC) therapy use and the risk of outcomes remains unclear. Objective To analyse the epidemiology of PAD in a large cohort of European and Asian AF patients, and the impact on treatment patterns and risks of adverse outcomes. Methods We analysed AF patients from two large prospective observational registries. We identified patients with PAD as reported by the investigators. Logistic regression analysis was used to assess factor associated with the presence of PAD at baseline. OAC prescription and risk of outcomes were analyzed according to the presence of PAD, using adjusted Logistic and Cox regression analyses. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). Interaction analyses were also performed according to different subgroups. Results 15,497 patients with AF (mean age 68.9, SD 11.6 years; 38.6% female, 30% from Asia) were included in the analysis. PAD was found in 941 patients (6.1%), with higher prevalence among European individuals compared to Asian (8.1% vs 1.2%, p&amp;lt;0.001). Patients with PAD were older, more likely with permanent AF, more symptomatic and with higher thromboembolic and bleeding risk. On logistic regression analysis, European patients had 6-fold higher odds of presenting with PAD compared with Asians (Figure 1, Panel A). Other comorbidities and increasing age were associated with higher odds of prevalent PAD (Figure 1 Panel A). Conversely, female sex was associated with lower odds of having PAD at baseline. With age modelled as a continuous variable, and odds of PAD at baseline, there was a non-linear relationship, with the odds of PAD increasing almost linearly until 70 years, plateauing afterwards (Figure 1 Panel B). After adjustments, PAD was associated with lower use of OAC (OR 0.69, 95% CI 0.57-0.85). On Cox regression analysis, PAD was associated with a higher risk of the primary composite outcome (HR 1.28, 95%CI: 1.08-1.52) and all-cause death (HR 1.40, 95%CI: 1.16-1.69). A significant interaction was observed between PAD and age, with greater risks of PAD found in younger patients (&amp;lt;65 years) for the primary outcome (pint=0.014, Figure 2, panel A). Consistent results were observed when we analysed the interaction between PAD and age, modelled as a restricted cubic spline, where the risk of the primary outcome followed a J-curve across age, while patients without PAD showed an approximately linear relationship (pint&amp;lt;0.001, Figure 2, Panel B). Conclusions In patients with AF, PAD is associated with lower use of OAC and higher risk of adverse outcomes, with a greater risk seen in younger patients.Figure 1Figure 2

Assessment of right ventricular ejection fraction cut-point for predicting mortality and heart failure hospitalization in asian patients with heart failure and reduced ejection fraction (HFrEF)

Abstract Background Left ventricular ejection fraction (LVEF) has been well established as a predictor of morbidity and mortality in heart failure patients (HF). Meta-analyses have confirmed that right ventricular systolic dysfunction (RVSD) identified by cardiac MR predicts adverse outcomes in HF patients. However, the cut-point and predictive value of right ventricular ejection fraction (RVEF) in Asian patients remain unknown. Objectives To evaluate the RVEF cut-point for RVSD and demonstrate the association between RVSD by cardiac MR and a composite endpoint consisting of HF hospitalisation and/or all-cause mortality in HFrEF patients (LVEF ≤40%). Materials &amp; Methods A retrospective chart review of 370 consecutive HFrEF patients who underwent cardiac MR between 01 June 2009 and 31 December 2013 was done. The primary outcome was defined as all-cause mortality and/or HF hospitalisation. Receiver Operating Characteristic (ROC) analysis was done to explore the most accurate RVEF as a cut-point for RVSD. Multivariate Cox regression analysis was calculated. Results Patients were followed for a total of 1,989 patient-years with an average of 5.4 ± 2.9 years. The primary outcome occurred in 112 patients (30.3%). ROC analysis demonstrated that RVEF &amp;lt;48% provided the most accurate prognostic value (specificity 52%, sensitivity 70%) with an area under the curve of 0.62 (95% CI 0.55 – 0.69). Multivariate Cox analysis showed that RVSD was a significant independent risk factor (hazard ratio 1.71; 95% CI 1.10 – 2.66; p=0.018) for the primary outcome, in addition to age (p&amp;lt;0.001), New York Heart Association functional class (p&amp;lt;0.001), and diabetes mellitus (p=0.014), regardless of LVEF. Conclusions In Asian HFrEF patients, RVSD defined by RVEF &amp;lt;48% by cardiac MR can predict adverse events and provide a prognostic parameter for risk stratification.

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p &amp;lt; 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p &amp;lt; 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p &amp;lt; 0.001 and HR 1.12, p &amp;lt; 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p &amp;lt; 0.001 and HR 6.99, p &amp;lt; 0.001), cardiogenic shock (HR 26.3, p &amp;lt; 0.001, HR 12.0, p &amp;lt; 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p &amp;lt; 0.001, HR 18.1, p &amp;lt; 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p &amp;lt; 0.001) and (HR 62.7, p &amp;lt; 0.007; HR 18.9, p &amp;lt; 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

An external validation of DOAC score in patients with atrial fibrillation following transcatheter aortic valve replacement

Abstract Background Bleeding events, particularly in patients with atrial fibrillation (AF) and those with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), are a major clinical concern and are associated with a worse prognosis. The DOAC Score (1) has recently been introduced to predict bleeding risk in patients with AF taking direct oral anticoagulants (DOACs). However, further validation is required to confirm its ability. Objective This study aims to evaluate the predictive ability of the DOAC Score for bleeding events in Asian patients with AF undergoing TAVR. Methods In this multicentre, retrospective, observational cohort study, patients with AF who underwent TAVR were included. The data was obtained from the Japanese multicentre registry, which comprises 19 centres from 2013 to 2019. Bleeding was defined as any post-discharge bleeding after TAVR. The primary endpoint was the incidence of all bleeding events in 3 populations: the overall population, the DOAC cohort, and the vitamin K antagonist (VKA) cohort. Results This study included 1230 patients with a mean age of 84.6 ± 5.1 years, of whom 457 were males. Among them, 465 patients (37.8%) were treated with a VKA while the rest were treated with a DOAC. Patients were divided into three groups according to their DOAC Score: 380 patients (30.1%) were in the ≤ moderate risk group with a DOAC Score of 7 or less, 497 patients (40.4%) were in the high-risk group with a DOAC Score of 8 or 9, and 353 patients (28.7%) were in the very high-risk group with a DOAC Score over 10. The cumulative incidence of all bleeding at 5 years in the overall population was significantly different in the 3 risk groups: ≤ moderate: 8.4%, high-risk: 10.8%, very high-risk: 21.6%, respectively (p&amp;lt; 0.01). The incidence was also significantly different in the DOAC and VKA cohorts (p&amp;lt;0.01 and p=0.03, respectively). Conclusion The recently published DOAC Score is well predictive of bleeding risk in Asian patients with AF after TAVR. The score may be useful in predicting bleeding in patients taking both DOAC and VKA.Graphical abstract

Transcatheter aortic valve replacement with balloon-expandable and self-expandable valves in Japanese patients with large annulus: the OCEAN-TAVI registry

Abstract Background East Asians have smaller aortic valve complexes than individuals from Western countries, and few studies have reported transcatheter aortic valve replacement (TAVR) outcomes in Asian patients with a large annulus. Purpose We aimed to compare the acute and long-term outcomes of TAVR using balloon-expandable valves (BEVs) and self-expandable valves (SEVs) in Asian patients with a large annulus. Methods We retrospectively analyzed the data from the Optimized transCathEter vAlvular interveNtion Transcatheter Aortic Valve Implantation (OCEAN-TAVI) registry. A large annulus was defined by annular area ≥ 500 mm2 and average diameter ≥ 25 mm in computed tomography scans. The primary endpoint was the 3-year all-cause mortality. Secondary endpoints were 3-year heart-failure rehospitalization (HFR) after TAVR, acute outcomes of TAVR, and changes in valve function on echocardiography 2 years after TAVR. Results Among 773 patients, 671 (86.8%) underwent BEV-TAVR. The SEV-TAVR group showed a significantly higher incidence of above-moderate perivalvular leakage (2.1% vs. 7.8%; P &amp;lt; 0.001), and included a significantly greater percentage of patients who required postoperative pacemaker implantation (6.1% vs. 11.8%; P = 0.035). The incidence of moderate-to-severe prosthesis–patient mismatch did not differ between the two groups. The Kaplan–Meier curve showed no significant intergroup differences in the 3-year all-cause mortality and HFR rates (log-rank P = 0.900), and the echocardiography-indexed effective orifice area and mean transaortic valve pressure gradient at 2 years post-TAVR did not differ significantly between the two groups. Conclusions The benefits of BEV-TAVR may outweigh those of SEV-TAVR in patients with a large annulus.

Switching from warfarin to a DOAC in frail elderly asian patients with atrial fibrillation: a nationwide population-based study

Abstract Background Recently, switching international normalized ratio guided warfarin management to a direct oral anticoagulant (DOAC) was associated with more bleeding complications than maintaining warfarin in frail elderly patients with atrial fibrillation (AF). However, there is a paucity of information on whether these results could be applied to Asian patients with AF, who are known to have relatively low time in therapeutic range (TTR) levels. Purpose To evaluate the safety and effectiveness of switching from warfarin to a DOAC in frail elderly Asian patients with AF. Methods Using a Korean health insurance database, we included patients with AF who were prescribed warfarin between January 2013 and August 2015 without significant bleeding or thromboembolic events during the window period, specifically those aged 75 or older with a Hospital Frailty Risk Score of 5 or more. Those who switched to DOACs during the window period were categorized as the DOAC group and those who continued with warfarin were categorized as the warfarin group. The primary outcome was defined as the composite of major bleeding (MB) and clinically relevant non-major bleeding (CRNMB), and secondary outcomes were defined as thromboembolic events, all-cause death, the composite of MB, CRNMB and ischemic stroke (so-called net clinical outcome [NCO]). The propensity score weighting method was utilized to compare the two groups. Results A total of 12,162 patients were included (8,108 with maintaining warfarin, 4,054 with switching to a DOAC). Baseline characteristics were well-balanced after the inverse probability of treatment weighting (mean age, 80 years; men, 50%; and mean CHA₂DS₂-VASc score, 5.6). Compared with maintaining warfarin, switching to a DOAC was associated with significantly higher risks of the primary outcome (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.09-1.87, p=0.01), thromboembolic events (1.28, 1.01-1.62, p=0.039), all-cause death (1.38, 1.15-1.66, p&amp;lt;0.001) and the NCO (1.26, 1.01-1.58, p=0.04). (Figure A, Figure B), whereas there was no difference in the risk of intracerebral hemorrhage (0.90, 0.50-1.60, p=0.7157). When comparing each DOAC with maintaining warfarin, switching to rivaroxaban was associated with a higher risk of the composite of MB and CRNMB (1.91, 1.38-2.64, p&amp;lt;0.001) and thromboembolic events (1.40, 1.03-1.91, p=0.034) than maintaining warfarin. Conclusion In line with the non-Asian population, switching to a DOAC was associated with a significantly higher risk of MB or CRNMB, thromboembolic events, all-cause death and NCO compared with maintaining warfarin in frail elderly Asian patients with AF. Therefore, even in Asians, switching to a DOAC should be considered more cautiously in patients who are stably managed on warfarin.

A systematic review and meta-analysis on the predictive value of the C2HEST score to predict new onset atrial fibrillation in &amp;gt;11 million Western and Asian subjects

Abstract Background The incidence of new-onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long-term prognosis. The C2HEST score has been recently proposed to stratify the NOAF risk. The C2HEST score includes coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age ≥ 75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). Pooled data on the performance of the C2HEST score are lacking, as well as its performance in different subgroups of patients. Methods Systematic review and metanalysis of observational studies reporting data on NOAF according to the C2HEST score. We searched PubMed, Web of Science and Google scholar databases. Metanalysis of the area under the curve (AUC) with 95% confidence interval (95%CI) was performed. We performed a sensitivity analysis on 1) subjects from the general population/primary care and 2) patients with cardiac disease, 3) Asian patients, 4) Western patients. The risk of bias (RoB) analysis was performed with the Cochrane RoBINS tool for observational studies, evaluating the following domains: bias due to confounding, to selection of participants, in classification of interventions, to deviations from intended interventions, due to missing data, in measurement of outcomes and in selection of the reported result. Results Strategy search retrieved 360 articles. Of these, 17 studies were included, accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The pooled analysis gave an AUC of 0.70 (95%CI 0.66-0.74) with high heterogeneity. A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95%CI 0.64-0.75). In the subgroup of patients with cardiovascular disease, the AUC for the C2HEST score was 0.71 (0.69-0.79). The C2HEST score performed similarly in Asian (AUC 0.72, 95%CI 0.68-0.77), and in Western patients (AUC 0.68, 95%CI 0.62-0.75). We also performed a metanalysis of the Hazar ratios (HR) for different cut-offs of the C2HEST score. A C2HEST score &amp;gt;1 yielded an HR of 3.98 (95%CI 2.40-6.60), a C2HEST score &amp;gt;2 an HR of 5.63 (95%CI 2.78-11.42) and a C2HEST score &amp;gt;3 an HR of 5.02 (95%CI 2.64-9.54). Conclusion The C2HEST score shows a good performance in predicting NOAF in primary and secondary prevention studies. Furthermore, its predictive value is similar between Western and Asian subjects, making it widely usable in clinical practice. More data in other high-risk subgroups of patients such as those with stroke and after cardioversion-ablation patients are needed.

Intraindividual variability in lipoprotein(a): the value of a repeat measure for reclassifying individuals at intermediate-risk

Abstract Background Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease and outcomes. Levels are predominantly genetically determined and repeat measurements are traditionally considered unlikely to be useful. However, the temporal variation of Lp(a) is not well characterized and it is unclear whether a single measure of Lp(a) is sufficient to assess cardiovascular risk in all individuals. Purpose To determine the intraindividual variability of Lp(a) and whether a repeated measure reclassified Lp(a)-specific cardiovascular risk using the European Atherosclerosis Society (EAS) consensus statement risk categories. Methods This retrospective cohort study analyzed initial and repeated Lp(a) measures obtained using the same laboratory assay from 609 individuals in the Nashville Biosciences database accessed through the American Heart Association Precision Medicine Platform. Categorical variables are presented as counts (%) and compared using Fisher’s exact test. Continuous variables are presented as mean ± standard deviation or median (Q1-Q3), tested for normality using the Shapiro-Wilk test, and compared using parametric and nonparametric tests where appropriate. The Spearman’s Rank correlation coefficient was used to assess the relationship between two variables. The significance level was set at p&amp;lt;0.05. Results Median age was 52.5 (37.1-62.8) years, 45% were women, 80.3% were White patients, 13.3% were Black patients, 1.6% were Asian patients, and 4.8% were other/unknown patients. In terms of relevant comorbidities, 41% had ischemic heart disease, 24.1% had chronic kidney disease, and 13.5% had liver disease. The median time between the two Lp(a) measures was 1.07 (0.5-2.1) years. Our analysis shows a significant difference between the paired Lp(a) values (p&amp;lt;0.05), with 38.1% [95% CI 34.2%-42%] changing by ≥10mg/dL, and 40.5% [95%CI 36.6%-44.3%] changing by &amp;gt;25%. There was a positive correlation between the baseline Lp(a) levels and the absolute changes in Lp(a), (r=0.59, p&amp;lt;0.01). The proportions of individuals with variability are similar in those who were never on the potentially Lp(a)-altering agents (statin, niacin, or PCSK9 inhibitor drugs) (n=91), with 32% [95%CI 22.4%-41.6%] changing by ≥10mg/dL, and 34% [95%CI 24.3%-43.7%] changing by &amp;gt;25%. While over 90% of those whose values were initially in the EAS low-risk and high-risk categories remained in those categories, 53% of those in the intermediate "grey-zone" category transitioned to either the low (20%)- or the high (33%)- risk category (Figure). Conclusion(s) Temporal-related changes in Lp(a) variability were present in many individuals and should be included in calculating the expected effect sizes in future studies targeting Lp(a). A repeat Lp(a) measure may allow more precise Lp(a)-specific cardiovascular risk prediction for individuals whose initial value is in the EAS-defined intermediate "grey-zone" category.

Inter-ethnic heterogeneity in valvular morphology and aortopathy of a worldwide bicuspid aortic valve cohort referred for TAVR

Abstract Background Bicuspid aortic valve (BAV) represents one of the most common congenital heart disease. BAV stenosis tipycally occurs in younger, low-surgical risk patients compared to tricuspid aortic valves (TAV). With the predicted expansion of trans-catheter aortic valve replacement (TAVR) into lower-risk patients, the proportion of BAV is expected to rise. Although some observational studies have investigated the characteristics of Asian versus European patients with BAV undergoing TAVR, little is known about the inter-ethnic differences within the large and diverse Asian, African, Russian, and Caucasian population. Purpose To evaluate the inter-ethnic differences of aortic valve morphology, annular size and associated aortopathy, in a worldwide population of patients with severe aortic stenosis referred for TAVR. Methods Cardiovascular multislice computed tomography data of patients with severe aortic valve stenosis referred for TAVR worldwide were obtained from the database of the Meril Life Core Lab. Inter-ethnic and epidemiological differences in terms of valvular phenotype, annular size and aortic morphology were evaluated with particular focus on patients with BAV. Results Among 12,712 patients (59% male), n=3,203 subjects (25%) exhibited a BAV morphology. According to the Siever’s BAV classification, type 1 (71%, n=2,284) was the most prevalent BAV morphology and particularly Type 1a was the most common in almost all population, with 26% exhibiting a type 0 BAV, while only 3% of the patients (n= 92) had a type 2 (Table 1). A significantly higher prevalence of severe calcium score (&amp;gt;1000 mm3) was found in patients with BAV compared with patients exhibiting a TAV morphology (51% vs. 32, p&amp;lt;0.01). Additionally, larger ascending aorta (AA) diameter (AA &amp;gt;40 mm) (BAV: 31% vs TAV 7%, p = 0.04), along with a higher prevalence of horizontal aorta (HA) (BAV: 20% vs TAV: 9%, p&amp;lt;0.01) was found in patients with BAV compared with TAV. As for inter-ethnic characteristics, there was a higher prevalence of BAV in Indian and Asian Pacific populations (respectively 43% and 28%), with the African population exhibiting the lowest prevalence (7%, n= 28, p=0.02) (Table 2). In Indian patients a higher prevalence of BAV was found in an earlier age (61-70 years old) compared to Western countries (p=0.05). Finally, smaller annular size (456±98 mm2 vs 584±99 mm2, p&amp;lt;0.01) and lower coronary ostia height (Asia and India: RCA 14.5±3 mm, LCA 14±2.9mm vs Caucasian and Russian: RCA 16±3.2 mm, LCA 16.9±3.3mm; p&amp;lt;0.01) were found in the Asian and Indian population when compared with Russian, African and Caucasian subjects. Conclusions BAV morphology, aortopathy and annular size resulted widely heterogenous according to the ethnicity and geographical origin of patients referred for TAVR worldwide. These features may lead different therapeutical decision making and outcomes following TAVR in patients with BAV.Table 1Table 2

Identification of genetic variants by using a whole exome sequencing approach in Taiwanese patients with Brugada Syndrome

Abstract Background Brugada Syndrome (BrS) is a life-threatening arrhythmia disease primarily affecting young men. Many genetic studies have been conducted mainly in Caucasian BrS patients to identify potential genetic drivers. SCN5A mutations are less common in Asian BrS patients (around 10%) compared to Caucasian patients (20-30%). This means the pathogenic process of more than 70% of BrS patients remains unclear. With the advancement in NGS technologies, we can conduct genome-wide screening of DNA variants in BrS patients efficiently. Purpose Since less than 30% of the BrS patients have known genetic drivers for the disease, we aimed to identify more DNA variants in BrS patients by using the whole exome sequencing (WES) approach. Furthermore, we evaluated the landscape of DNA variants in the two groups of BrS patients according to whether they have SCN5A mutations or not. Methods A total of 201 BrS patients were recruited for the WES experiments. After obtaining the raw sequencing data, we performed the quality check procedures using the multiQC and Trimmomatic softwares (Figure 1). For reads passing the quality check, the BWA algorithm was used for the alignment. Next, the samtools, bamtools, and Picard methods were used to remove duplicates and perform the sorting. Subsequently, those sorted sequencing files were used to call the DNA variants by using the GATK approach and annotate them using the ANNOVAR method. The 201 BrS patients were classified into two different groups based on their mutation status of SCN5A, presentation of sudden cardiac death (SCD), and SCD along with syncope. The gene-based algorithm, SKAT, was used to analyze the summarized effects of DNA variants located in a single gene. For each DNA variant, Fisher's exact test was used to compare the allele frequency in the BrS patients under their groupings. Results The WES approach in the 201 BrS patients revealed a total of 205,454 variants, which were further categorized into two groups, common variants (51,867) and rare variants (153,587), based on their allele frequencies (5%). The SKAT algorithm was performed in the 30 genes that have been previously reported to be associated with BrS. No significant differences were observed in any gene in BrS patients for the common variants. Intriguingly, KCNJ8, SCN1B, ZFPM2, MAPRE2, and KCNE5 showed significant differences in allele frequencies between the SCN5A+ and SCN5A- patients (Figure 2). Fisher's exact test further revealed that three DNA variants (chr19:35524980, chr12:21926440, chr6:126210346) were significantly enriched in SCN5A+ patients. The 5 DNA variants located in ZFPM2 showed a linkage disequilibrium block and were enriched in SCN5A+ patients. Conclusions The WES approach in BrS patients revealed DNA variants that were reported in previous studies. Several DNA variants were significantly enriched in SCN5A+ patients, suggesting that the genome-wide mutation landscape was different in SCN5A+ and SCN5A- BrS patients.Figure 1Figure 2

Impact of real-world off-label dose of Apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease

Abstract Background Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Objective The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD). Methods Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 635 patients with AF and CKD (76.9±10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P=0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=1.000; off-label overdose vs. standard dose, P=1.000; off-label underdose vs. off-label overdose, P=0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P=0.005). Conclusions Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.

Prediction of CRT response using a novel CRT responder score in an Asian patient population

Abstract Introduction Cardiac Resynchronization Therapy (CRT) guidelines, derived from trials among U.S. and European patients, assign weaker recommendations to those with midrange QRS duration (&amp;lt;150ms). Patient height and body size may modulate CRT efficacy. Moreover, these factors may affect CRT utilization and efficacy in Asia. Aim The purpose of this analysis was to determine the prediction scoring system model for CRT responders in a Japanese patient population. Methods We analyzed the database of the Multicenter Prospective Pilot Study to Test LV Intracardiac Conduction Time as a Predictor of CRT Response (BIO|SELECT) which was a single-arm study conducted at 28 hospitals in Japan. This study enrolled patients eligible for a de-novo CRT-defibrillator (CRT-D) based on current guideline indications, who had no recent or planned cardiac surgery and were planned to receive a Sentus ProMRI OTW quadripolar LV lead and a BIOTRONIK CRT-D with multipole pacing feature. Patients were followed for 7 months after implantation. Four accepted parameters to define CRT response [LVESV (cut-off -15%), LVEF (+5%), BNP (-25%), and NYHA class (one class improvement)] were combined into a composite benefit index (CBI) by forming the normalized sum, with CBI = 4.0 meaning response. The CBI was found to be more robust than the individual 4 parameters due to the reduced influence of noise and measurement errors in single parameters. Several factors were studied to create the scoring tool. The CRT responder score was the sum of these individual scores (range 0-100). To construct a predictive scoring system, logistic regression analysis was performed with a backward selection procedure. In addition, the Akaike information criterion (AIC) was applied to determine the best model among those tested. The score was then assigned employing the β coefficient of each variable divided by the reference value. The model's calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Results A total of 196 patients were enrolled in this study (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). The Ooccurrence of CRT response during the 7-month follow-up was 54%. Future CRT responders were significantly predicted by low age (&amp;lt; 70 years)(18 points), female (19 points), prior heart failure hospitalization (16 points), body mass index (&amp;lt;20) (17 points), QRS/height (&amp;lt;0.858)(30 points). This score predicted CRT response well (area under curve 0.72; 95% CI 0.643-0.798). When the cut-off of 63 points or more was applied the sensitivity was 0.56, the specificity was 0.72, and the negative predictive value was 0.58. Conclusions The CRT responder score is a novel approach for the prediction of CRT response, but should be validated and further improved to increase its predictive value. This approach highlights the role of preventing the development of severe heart failure and could help to identify individuals who might benefit from CRT.