Hazard Ratio Research Articles

Abstract 4119146: Pulmonary Artery Enlargement Predicts Mortality in Patients with Severe Aortic Stenosis after Transcatheter Aortic Valve Replacement.

Background: Pulmonary hypertension is associated with extensive remodeling of the pulmonary tree, with key finding the enlargement of the pulmonary artery (PA). Although the independent predictive value of the pulmonary hypertension in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis has been clearly demonstrated, data about the potential predictive value of the pre-interventional PA enlargement on mortality are scarce. Research questions: The aim of the present study was to assess the prognostic significance of the pre-interventional PA enlargement, assessed by cardiac CT scan, in patients undergoing transcatheter aortic valve replacement for severe aortic stenosis. Methods: We conducted a retrospective study and recruited 337 patients with aortic stenosis, who underwent a right heart catheterization and a cardiac CT scan before the transcatheter aortic valve replacement. The cohort was divided in two groups according to the presence of an enlarged PA (PA e ), (main PA axial diameter ≥ 29 mm for males and ≥ 27 mm for females, n=192, mean age 83±6 years, 41% males) or not (PA n ), ( n=145, mean age 84±6 years, 46% males). The primary endpoint was all-cause mortality at 1 year. Results: Globally, a strong correlation between invasive mean PA pressure and main PA axial diameter was noted (Pearson r=0.393, p<0 .001). Compared to the PA n group, patients with enlarged PA exhibited higher 1 year mortality rates (hazard ratio 2.51, 95% CI: 1.1-6.04, p=0.027). The prognostic significance was even stronger after indexing the PA to the ascending aorta diameter (hazard ratio 3.82, 95% CI: 1.86-7.87, p<0.001, figure 1). Conclusions: Pre interventional PA enlargement, is strongly associated with 1-year all-cause mortality in patients undergoing transcatheter aortic valve. This may pave the way for a more precise non-invasive risk stratification in patients with severe aortic stenosis.

Abstract 4122948: Lipoprotein(a) associated risk of atherosclerotic cardiovascular disease is independent of C-reactive protein

Background: Elevated lipoprotein(a), present in 1 in 5 individuals, is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent studies have reached contrasting conclusions on whether low-grade inflammation measured by elevated C-reactive protein (CRP) modifies the risk of ASCVD from high lipoprotein(a). We tested the hypothesis that high lipoprotein(a) associates with risk of recurrent ASCVD irrespective of elevated or low CRP. Additionally, we performed meta-analyses of previous studies on lipoprotein(a)-associated ASCVD risk stratified by CRP levels and by incident or recurrent events. Methods: We included 3,543 individuals with prevalent ASCVD from the Copenhagen General Population Study (CGPS), a contemporary, prospective Danish cohort study. Hazard ratios (HR) for ASCVD were examined using multivariable adjusted Cox regressions stratified by CRP (<2 mg/L and ≥2 mg/L). Random-effects meta-analyses in primary (incident events) and secondary (recurrent events) prevention were conducted separately, including studies on lipoprotein(a) and risk of ASCVD stratified by CRP. Results: During a median of 7.5 years of follow-up of 3,543 CGPS participants with established ASCVD, 1,425 experienced a recurrent ASCVD event. Multivariable adjusted HRs for ASCVD for high vs. low lipoprotein(a) were 1.41 (95% confidence interval: 1.19-1.67) and 1.31 (1.08-1.59) in individuals with low or elevated CRP with no evidence of effect modification (Figure 1A, p for interaction=0.11). When risk estimates for ASCVD were summarized in separate meta-analyses for primary and secondary prevention settings, a 50 mg/dL higher lipoprotein(a) was robustly associated with increased risk of ASCVD irrespective of CRP levels (Figure 1B). In primary prevention, a 50 mg/dL higher lipoprotein(a) associated with similar summary HRs of 1.18 (1.15-1.20) in low CRP vs. 1.16 (1.14-1.19) in elevated CRP, and likewise in secondary prevention settings, with similar HRs of 1.10 (1.07-1.14) and 1.14 (1.10-1.17), respectively. Conclusion: High lipoprotein(a) was associated with increased risk of ASCVD irrespective of CRP levels both in primary and secondary prevention settings.

Interleukin-1 Blockade in Patients With ST-Segment Elevation Myocardial Infarction Across the Spectrum of Coronary Artery Disease Complexity.

Patients with ST-segment elevation myocardial infarction (STEMI) and complex coronary artery disease (CAD) face a poor prognosis, including increased heart failure (HF) risk. Phase 2 clinical trials of anakinra have shown inhibition of the acute inflammatory response and prevention of HF after STEMI, but data on its effects based on CAD complexity are lacking. We performed a pooled secondary analysis of 139 patients with STEMI. The SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery), SYNTAX II and Gensini scores were calculated, and patients were divided into two groups below and above the median. We evaluated the effect of anakinra on the area-under-the-curve of high-sensitivity C-reactive protein (hsCRP-AUC) at 14 days, and the composite endpoint of new-onset HF, HF hospitalization, or all-cause death at 1-year follow-up using Kaplan-Meier survival curves, Cox regression analysis for Hazard Ratios (HR), and tested interactions between subgroups. All three CAD complexity scores (SYNTAX, SYNTAX II and Gensini) were associated with an increased risk of adverse events (HR 1.02 to 1.06, all p-values ≤0.025). We found no statistically significant interactions between CAD extent, measured as single-vessel or multi-vessel CAD, SYNTAX score ≤9 or >9, SYNTAX II score ≤24 or >24, Gensini score ≤32 or >32, and treatment effect of anakinra on hsCRP-AUC or the composite clinical endpoint (all p-values for interaction >0.05). In conclusion, among patients with STEMI, IL-1 blockade with anakinra significantly attenuated the acute inflammatory response and reduced the risk of HF-related events regardless of the spectrum of CAD complexity.

Abstract 4147625: Cardiometabolic Syndrome and Incident Alzheimer’s Disease: The Predicative Value of Age and CMS Using Cox and Machine Learning Models

Background: Cardiometabolic syndrome (CMS) poses a significant public health concern. The study aimed to investigate the predictive value of age and CMS for incident Alzheimer’s disease (AD) in women aged≥50. Methods: A cohort of women aged 50-79 ( n = 63,117) who participated in the Women’s Health Initiative Observational Study (WHIOS) in 1993-1998, without baseline AD and followed through to March 1, 2019, were analyzed. CMS was defined as having ≥3 of five CMS components: large waist circumference, HBP, elevated triglycerides, elevated glucose, and low HDL-cholesterol. AD was classified by physician-diagnoses of incident AD. Hazards ratios (HR) of AD risk associated with CMS by age were analyzed using Cox’s proportional hazards regression analysis. Machine learning (ML)-XGBoost and Lasso Cox models clustered individuals with low, mild, moderate, and severe risk of incident AD. Results: During a median follow-up of 20 years (range: 3.36 to 23.36 years), 8340 developed incident AD. The incident rate (95%CI) of AD was 8.6 (8.1-9.1) per 1000 person-years (PY) in women with CMS, and 7.0 (6.9-7.2) per 1000 PY in those without CMS (p<0.001). Multivariate Cox’s regression analysis indicated that women with CMS versus non-CMS had significantly higher risks of AD in those aged 50-59 [HR (95%CI): 1.37(1.12-1.68)], followed by in those aged 60-69 [1.26 (1.14-1.40)], but nonsignificant in those aged≥70 [1.00 (0.87-1.14)]. Elevated glucose concentration ranked as the top predictor for AD, followed by triglyceride and HBP. Four levels (low to severe) of AD risk were significantly clustered using ML-XGBoost and Lasso Cox models. Conclusions: Women aged 50-69 with CMS vs those without CMS had significantly higher relative risks of AD, but the risk was not significant in those aged≥70. The application of ML prediction models holds potential promise in the early identification of AD risk among U.S. adults.

Abstract 4134345: Diastolic Dysfunction And The Risk Of Stroke And Major Bleeding

Background: Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident ischemic stroke/transient ischemic attack (TIA) and with bleeding events is not well established. Aims: To examine the association of presence and severity of DD with the risk of incident ischemic stroke/TIA and major bleeding. Methods: A total of 219,667 patients who underwent at least one echocardiogram between 2010 and 2022 at a large academic institution and were followed for at least 3 months were included. Patients with prior history of stroke or TIA (n=21,505, 10%) were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups, based on the most severe DD assessment: Normal (n=113,265), grade I (n=21,981), grade II (n=7,215), and grade III (n=1,627). Patients in whom the presence of DD could not be determined (n=54,074) were excluded. The final study cohort (n=144,088) was followed to the endpoint of hospital admission for ischemic stroke/TIA or for major bleeding. Results: Over a median follow-up of 3.4 years, 3482 (2.4%) patients were hospitalized for stroke/TIA and 6994 (4.9%) for major bleeding. After adjusting for several confounding variables (Table), DD remained a strong predictor of incident stroke/TIA (hazard ratio (HR)=1.34 per grade increase in DD, p<0.001, Figure) and of major bleeding (HR=1.32 per grade increase in DD, p<0.001, Figure). These results were similar in patients with (n=11,508, 8%) or without prior history of atrial fibrillation. Conclusions: Patients with DD have a heightened risk of ischemic cerebrovascular accidents and major bleeding independent of the presence of atrial fibrillation. These risks escalate with the severity of DD. DD should be considered when counseling patients regarding their risk profile and management options.

Abstract 4135338: Associations between plant-based diets and total mortality among Chinese older participants with cardiometabolic diseases: a prospective cohort study

Background and Aims: Plant-based diets have been associated with a lower risk of total mortality among generally health populations. However, the associations of plant-based diets with total mortality remain unclear among older people with cardiometabolic diseases, who have an elevated risk of mortality. Methods: We prospectively followed 4,485 participants (mean age: 84 years) from the China Prospective Longitudinal Survey of Health and Longevity (2006-2018), who had cardiometabolic disease in 2006. Dietary data were collected at baseline using a food-frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), in which plant-based foods received positive scores while animal foods (meat, fish and aquatic products, eggs, milk, animal fats) received reversed scores accordingly. We also created a healthful plant-based diet index (hPDI), where healthy plant-based foods (whole grains, vegetables, vegetable oils, fresh fruits, legumes, beans, garlic, nuts, tea) received positive scores, while less healthy plant-based foods (refined grains, pickles, sugar, preserved vegetables) and animal-based foods were given reversed scores. In addition, an unhealthful plant-based diet index (uPDI) was created by assigning positive scores to less healthy plant-based foods while reverse scores to healthy plant-based foods and animal-based foods. We used Cox proportional hazards regression to compute hazard ratios (HRs) and 95% CIs for total mortality, with adjustment for demographics, dietary and lifestyle factors, and medical history. Results: During a 12 years of follow-up, 2,881 deaths were recorded. A higher score from PDI and hPDI was associated with a lower risk total mortality among participants with cardiometabolic diseases (HR and 95% CI for extreme quintiles of PDIs: 0.85, 95% CI 0.75–0.96, P trend < 0.001; hPDI: 0.84 (0.74–0.94), P trend < 0.001). A higher uPDI score was associated with a higher total mortality among participants with cardiometabolic diseases (uPDI: 1.28 (1.13-1.47), P trend < 0.001). These results were consistent in subgroup analyses by age, sex, smoking status, alcohol consumption, education level, physical activity, and BMI. Conclusion: Our study suggests that among older Chinese participants with cardiometabolic diseases, adherence to an overall plant-based diet or a healthful plant-based diet, is associated with a lower total mortality, while an unhealthful plant-based diet was associated with a higher total mortality.

Abstract 4120785: Differential Cardiovascular Impact of ω-3 Fatty Acid in Patients at High Cardiovascular Risk in Asians versus non-Asians: Sub-analysis of the STRENGTH Randomized Clinical Trial

Background: Racial differences in lipid and cardiovascular risk profiles are well-established including for Asians. The STRENGTH trial found that ω-3 carboxylic acid (CA) formulation of eicosapentaenoic acid and docosahexaenoic acid did not result in significant changes in cardiovascular event rates compared with corn oil in statin-treated patients at high cardiovascular risk, however drug efficacy may vary by race. We evaluated and compared the cardiovascular treatment effect of ω-3 CA between Asians and non-Asians in this sub-analysis of the STRENGTH trial. Methods: The STRENGTH trial was a double-blinded 1:1 randomized controlled trial of 13,078 high cardiovascular risk patients enrolled during 10/30/2014-6/14/2017 at 675 centers. Efficacy of ω-3 CA for Asians (n=1,355) and non-Asians (n=11,723) and interactions between race and treatment effect were assessed. The primary endpoint is a composite of cardiovascular death, non-fatal myocardial infarction, stroke, coronary revascularization and unstable angina hospitalizations. Results: Key differences in baseline characteristics include Asians having significantly higher prevalence of men, secondary prevention, and lower total cholesterol, LDL, apoB100, and hsCRP. In Asians, ω-3 CA was associated with significantly lower primary endpoint during follow-up, with 81/698 events [Kaplan-Meier (KM) Estimate: 14.8%] in the ω-3 CA group, 103/657 events (KM Estimate: 20.4%) in the corn oil group, and hazard ratio (HR) 0.72, 95% CI 0.54-0.96, P=0.026 (Figure A). In non-Asians, there was not a significant difference in primary endpoint rates between the two groups, with 704/5841 events (KM Estimate: 15.6%) in the ω-3 CA group, 692/5882 events (KM Estimate: 15.9%) in the corn oil group, and HR 1.03 95% CI 0.93-1.14, P=0.60 (Figure B). There were significant interactions between race (Asian versus non-Asian) and treatment group for the primary endpoint (P=0.021) and non-fatal stroke (P=0.016) and remained significant after adjusting for other covariates. Conclusion: ω-3 CA was associated with significant reduction in major adverse cardiovascular events compared with corn oil in Asians but not in non-Asian patients with high cardiovascular risk. Further research is necessary to elucidate the mechanisms for potentially beneficial effects of ω-3 CA unique to Asian race.

Abstract 4114276: Identification of the heterogeneity in the risk of heart failure in those with left bundle branch block pattern using artificial intelligence

Introduction: The association between left bundle branch block (LBBB) and heart failure is well-established. However, the lack of a practical risk assessment tool for patients with LBBB poses a clinical challenge to the management despite the heterogeneity of the LBBB population. Hypothesis: Artificial intelligence (AI) can extract features to stratify the risk of heart failure (HF) within the heterogeneity of LBBB. Methods: All 12-lead ECGs diagnosed with LBBB recorded from 1/1/2015 to 12/31/2019 were identified in our institution. ECG data were analyzed as 2D matrices with a shape of 12×2500. The Uniform Manifold Approximation and Projection (UMAP) was used to visualize the heterogeneity of LBBB ECG. Additionally, a 2-dimensional convolutional neural network model was trained to detect LBBB ECGs associated with past HF diagnosis. The model was then applied to ECGs from an external cohort of patients with LBBB but without a history of HF. Cumulative incidences of HF admission were compared by stratifying according to tertiles of the model output (low, intermediate and high AI score groups) Results: We identified 15,124 LBBB ECGs in our institution (training dataset) and 2,463 individuals with LBBB ECGs in the external cohort (external test dataset). The UMAP projection of the ECGs revealed distinct heterogeneity in the data ( Fig A ). This heterogeneity was not fully explained by patient demographics, ECG features, or institutions. When the external cohort was divided into 3 groups according to the tertile of AI prediction, patients with high AI scores had a higher risk of HF admission (high vs low AI score group: hazard ratio (HR), 2.10; 95% confidence interval (CI), 1.66-2.65; intermediate vs low AI score group: HR, 1.39; 95%CI, 1.08-1.78: log-rank p <0.0001; Fig 1B ). This finding was unchanged after adjusting for multiple clinical characteristics and ECG parameters, including QRS duration. Conclusion: We observed significant heterogeneity in ECGs presenting LBBB, and the AI model excellently stratified the risk of heart failure admission in patients with LBBB from a single recording of 12-lead ECG, suggesting great potential for clinical utility in managing patients with LBBB.

The expression of keratin 17 and p27 predicts clinical outcomes in colorectal cancer.

Keratin 17 (K17) is frequently overexpressed, associated with poor prognosis in various cancers, and contributes to p27 degradation during cancer progression. Using immunohistochemistry, we evaluated K17 and p27 expression and assessed their biological behavior and prognostic significance in 326 colorectal cancers. High K17 expression was associated with poorly differentiated tumors, high pT classification, and lymph node metastases. Low p27 expression was associated with large tumors, high pT classification, lymphovascular invasion, and lymph node metastases. The overall survival of patients with high K17 expression was significantly worse than that of patients with low K17 expression [hazard ratio (HR) = 1.805, 95% confidence interval (CI) 1.169-2.787; p = 0.007]. Patients with low p27 expression showed significantly worse overall survival than those with high p27 expression (HR = 3.082, 95% CI 1.722-5.517; p < 0.001). When combining the results of K17 and p27 expression, the K17highp27low expression group showed the worst overall survival. On the contrary, the K17high/lowp27high group showed the best overall survival (p < 0.001). Therefore, K17highp27low expression is an independent poor prognostic factor in colorectal cancer. Thus, high K17 and low p27 expression correlate with aggressive clinicopathologic behavior and can be used as poor prognostic markers in colorectal cancer.

Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial.

Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90th percentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.

Impact of major depressive disorder on breast cancer outcomes: a national retrospective cohort study.

Establishing whether women with major depressive disorder (MDD) who develop breast cancer (BC) have poor outcomes is key to optimizing care for this population. To address this, we examined associations between MDD and BC recurrence and mortality. Using medical record data from the Veterans Affairs Healthcare System, we established a retrospective cohort of women with local or regional stage invasive BC between 2010 and 2019 and followed through 2022. We used a two-year window to identify women diagnosed with MDD prior to BC diagnosis. We used multivariable Cox-proportional hazards regression to estimate associations between MDD and BC recurrence and mortality while accounting for competing-risks and adjusting for sociodemographic, clinical, lifestyle, and tumor characteristics. We identified 6,051 women with BC, of whom 1,754 (29%) had MDD. The mean age at BC diagnosis was 57 years (standard deviation = 11). In multivariable analyses, women with MDD had a 37% (hazard ratio (HR)=1.37; 95% confidence interval (CI): 1.19-1.57) higher risk of recurrence and a 30% (HR = 1.30; 95% CI: 1.02-1.64) higher risk of BC mortality. The association between MDD and recurrence was stronger among women with estrogen receptor-positive BC. In secondary analyses, there were significant interactions between MDD and multiple exposures with respect to recurrence, including current smoking, substance abuse, and non-receipt of screening mammography. Women with MDD had inferior BC outcomes compared to women without a history of MDD. Research is needed to investigate underlying mechanisms linking depression to BC progression and evaluate interventions to improve outcomes in this high-risk population.

Abstract 4132159: Dietary Intake of Niacin and Risk of Cardiovascular Mortality in The Golestan Cohort Study

Introduction: Recent studies have linked niacin metabolism with vascular inflammation and cardiovascular disease (CVD); however, the association is still inconclusive regarding dietary intake, and the findings may not be generalizable to various populations. In this longitudinal study within a Middle Eastern population, we aimed to assess the relationship between dietary intake of B vitamins, including niacin, and the risk of CVD mortality. Methods: Our study utilized data from the Golestan Cohort Study, which has tracked 50,045 participants aged 40-75 years since 2004. We excluded subjects who reported extreme total energy intake or had a positive history of cancer, CVD, or diabetes at baseline. Vitamin B intake estimations including thiamin, riboflavin, niacin, pyridoxamine, folate, and cobalamin intake were derived from the baseline food frequency questionnaire, noting that supplement use was uncommon in this cohort. To adjust for calorie intakes, we employed the nutrient density method. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for cardiovascular mortality, using the lowest quintile of intake as the reference group for vitamins and adjusting for potential confounders. Results: We analyzed 42,456 subjects with a mean age of 51.5 ± 8.7 years at baseline. During 579,339 person-years of follow-up (median: 14.1 years), 3,065 CVD deaths were recorded. The median dietary intake of niacin was 25.3 mg/d (Recommended Dietary Allowance = 14-16 mg/d). We observed significant associations between niacin intake (HR Q5 vs. Q1 = 1.13, 95% CI = 1.01-1.26, P trend &lt;0.05) and CVD mortality. When niacin was modeled as a continuous linear variable, it was associated with a greater risk of CVD mortality (HR = 1.05, 95% CI = 1.01-1.09) per 2 mg/1000Kcal/d increase. None of the other B vitamin intakes evaluated were associated with CVD mortality in this population. Conclusion: These findings suggest that among B vitamins, only dietary niacin intake was positively associated with CVD mortality. Further confirmation in larger studies is needed.

Neutrophil-to-lymphocyte ratio (NLR) at diagnosis in essential thrombocythemia: A new promising predictor of thrombotic events.

Myeloproliferative neoplasms represent a heterogeneous group of acquired hematopoietic stem cell diseases in which chronic inflammation is essential for both clonal evolution and thrombotic complications. The neutrophil-to-lymphocyte ratio (NLR), reflecting the imbalance between systemic inflammation and immunity, is emerging as a prognostic biomarker in several diseases, including hematological ones. A total of 473 patients with essential thrombocythemia (ET), the relationship between NLR value at diagnosis and the risk of thrombotic events in the follow-up, in addition to conventional clinical and biological variables, were retrospectively analyzed. A total of 78 thrombotic events were reported for an incidence rate of 1.8 × 100 patients/year. In multivariate analysis, NLR value≥4 at diagnosis was associated with higher cumulative thrombotic risk (hazard ratio [HR], 2.05; 95% CI, 1.29-2.28; p=.0001) as well International Prognostic Score for Thrombosis in Essential Thrombosis score intermediate-high (HR, 2.69; 95% CI, 1.27-5.72; p=.01) and diabetes (HR, 2.49; 95% CI, 1.23-3.05; p=.010). Concerning arterial thrombotic events, in multivariate analysis, NLR value at diagnosis ≥4 was predictive for thrombosis (HR, 2.13; 95% CI, 1.31-4.04; p=.001 as well diabetes (HR, 2.44; 95% CI, 1.05-5.68; p=.04) and hypertension (HR, 2.46; 95% CI, 1.05-5.68; p=.01). About venous thrombotic events, NLR value≥5 was a marker predictive for venous thrombosis (HR, 2.99; 95% CI, 2.45-6.48; p=.01) as well age >60 years old (HR, 2.26; 95% CI, 1.0-5.10; p=.05). NLR value is a simple, cost-effective, and easy-to-obtain inflammatory marker that can predict a diagnosis the risk of thrombosis in ET. Our results suggest that NLR value could be integrated into conventional cardiovascular risk scores, to better classify high-risk patients who are candidates for cytoreductive therapy. Further larger and prospective studies are warranted.

Abstract 4119472: Predictors of Sudden Cardiac Death in Patients with Atrial Fibrillation and No Apparent Risk Factor of Sudden Cardiac Death

Background: Atrial fibrillation (AF) is associated with sudden cardiac death (SCD). It is known that AF is associated with multiple traditional risk factors of SCD, such as coronary artery disease (CAD), history of myocardial infarction (MI), left ventricular hypertrophy (LVH) and low left ventricular ejection fraction (LVEF). However, AF per se could predispose SCD not mediated by these cardiovascular risk factors, and predictors of SCD in AF patients without these apparent SCD risk factors are unknown. Methods: Using the NTUH iMED database, AF patients without apparent SCD risk factors were longitudinal followed up from Jan. 2010 to Dec. 2021. The primary outcome was implantation of implantable cardioverter defibrillator (ICD) due to SCD. Cox regression was used to identify the predictors of SCD. Results: A total of 11250 AF patients without cardiovascular SCD risk factors and LVEF ≥55 % were longitudinally followed up. We first found CHA2DS2-VASc score did not predict SCD event. We found male gender (hazard ratio [HR ] 1.71 [1.05-2.78 ], p =0.032), hyperthyroidism (HR 3.50 [1.40-8.77 ], p=0.007）and paroxysmal AF (PAF)(HR 2.86 [1.63-5.04 ], p&lt;0.001）were associated with higher SCD risks. We created a AFSCD score using these parameters. We found SCD risk incrementally increased with increasing AFSCD score (p &lt;0.001 for trend). Patients with highest score (5 points) had more than 3-fold SCD risk compared with those with 0-point score (1.18 % person-year vs 0.36 %, p&lt;0.001). The C statistic of AFSCD score was significantly higher than CHA2DS2-VASc score (0.64 [0.57-0.70] vs 0.40 [0.33-0.48], p &lt;0.01). Conclusions: Male gender, hyperthyroid AF and PAF were predictors of incident SCD in AF patients and AFSCD scoring scheme based on these risk factors could possibly be implemented in clinical practice.

Abstract 4122247: Impact of serum chloride levels for ventricular arrhythmias in patients with heart failure undergoing cardiac resynchronization therapy

Background: As previous reports of ventricular arrhythmia (VA) as a prognostic marker of mortality in heart failure (HF) patients included those with implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) devices, little is known about the risk factors of VA among patients undergoing cardiac resynchronization therapy (CRT), especially those without previous VA. The prognostic role of electrolyte abnormalities has been highlighted in HF patients. This study evaluated the impact of serum chloride levels for VA and all-cause death in patients with HF who underwent CRT without VA before CRT implantation. Methods: From the retrospective cohort of 397 HF patients (age 63+/-13, male 74%) who undergoing CRT implantation between 2010 and 2020, this study enrolled 175 patients (82% implanted CRT with a defibrillator) without a previous history of VA (sustained ventricular tachycardia (VT) of ventricular fibrillation (VF)). We studied the impact of serum chloride levels before CRT implantation. The primary endpoint was defined as VA, VA with ICD therapy and sudden cardiac death. The secondary endpoint was all-cause mortality. Results: During median follow-up of 35 months, 53 patients (30%) experienced VA. Patients with VA had a tendency toward high LVESV (172ml vs. 150ml, p&lt;0.09) and low left ventricular ejection fraction (26 vs. 29, p&lt;0.09), and significantly reduced rate of angiotensin converting enzyme inhibitors or angiotensin receptor blockers (30% vs. 70%, p&lt;0.05) at the time of CRT implantation. The rate of CRT responders was significantly higher in patients without VA than with VA (59% vs. 40%, p&lt;0.05). The cut-off value of chloride for VA was determined to be 102mEq/l using receiver operating characteristic analysis. The patients with chloride ≤102mEq/l had significantly higher rates of VA (41% vs. 25%, log-rank p&lt;0.05) and mortality (33% vs. 18%, log-rank p&lt;0.05) (Figure). By multivariate cox analysis, the level of chloride had an independent predictive value of VA in patients with CRT (hazard ratio [HR] 1.08 per 1mEq/l decrease, 95% confidence interval [CI] 1.00-1.16, p&lt;0.05) (Table). Conclusions: The chloride level had a predictive value for VA after CRT implantation in HF patients without previous VA. The management of electrolytes, including chloride, might be important for preventing fatal arrhythmia in patients with HF undergoing CRT implantation.

Associations Among Sleep Apnea, Objective or Subjective Sleep Duration, and Recurrence of Atrial Fibrillation in Patients Who Undergo Radiofrequency Catheter Ablation for Persistent Atrial Fibrillation - A Prospective Observational Study.

Sleep apnea (SA), subjective sleep duration (SSD), and objective sleep duration (OSD) were reported as risk factors for atrial fibrillation (AF). However, the association between AF and the combination of SA and OSD has not been clarified. Nor has a mismatch between SSD and OSD been investigated. We assessed SA with polysomnography, OSD with actigraphy, and SSD in patients who underwent radiofrequency catheter ablation for persistent AF. We investigated associations among SA, OSD, OSD×3% oxygen desaturation index (3%ODI), and AF recurrence, considering SSD-OSD (i.e., the difference between SSD and OSD) and OSD. Seventy of 94 (74.4%) participants had moderate-to-severe SA (apnea-hypopnea index [AHI] ≥15). Participants were classified into OSD tertiles. Participants in Tertile 3 (mean OSD: 7.3 h) had decreased SSD-OSD (0.0 h) with increased Stage N1 sleep. Over 27.6 months, 10 AF recurrences occurred in 51 participants without treatment for SA. AHI ≥20 and OSD Tertile 3 were associated with AF recurrence (hazard ratios 5.7 [95% confidence interval 1.1-24.7] and 10.3 [95% confidence interval 1.2-88.4], respectively). Participants with AF recurrence had a higher OSD×3%ODI. SA and long OSD were predictors of recurrent AF through long exposure to intermittent hypoxia during sleep. SSD-OSD was low in patients with long OSD, possibly because of decreased sleep quality.

Abstract 4124931: Usefulness of the AHEAD Score for Prediction of All-cause Death in Patients With Acute and Chronic Coronary Syndromes

Background: The AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been introduced to predict all-cause death (ACD) in patients with heart failure. There is no information available on the utility of this score for the prediction of ACD in patients with coronary artery disease (CAD). Hypothesis: The AHEAD score may provide superior predictive value for ACD compared to the CHADS 2 score, which has been reported to be useful for predicting poor clinical outcomes in patients with acute (ACS) and chronic coronary syndromes (CCS). Methods: This retrospective multicenter cohort study analyzed data of the patients who underwent percutaneous coronary intervention for ACS or CCS between April 2013 and March 2019 using the Clinical Deep Data Accumulation System (CLIDAS) database. The AHEAD score was calculated by assigning 1 point each for atrial fibrillation, hemoglobin &lt;13 mg/dL for men and &lt;12 mg/dL for women, age &gt;70 years, elevated creatinine levels (&gt;130 μmol/L), and diabetes mellitus. The CHADS 2 score was calculated as previously reported. The study endpoint was ACD. Results: In total, 9,033 patients were enrolled (median age, 72 years; 77% male; 3,920 with ACS and 5,113 with CCS). Higher AHEAD or CHADS 2 scores were significantly associated with a higher rate of left main disease or three-vessel disease in both patients with ACS and CCS. In addition, after accounting for multiple variables using Cox multivariate analysis, both the AHEAD (hazard ratio [HR], 1.83 [95% confidence interval, 1.63–2.06] for ACS and 1.66 [1.49–1.85] for CCS) and CHADS 2 scores (HR 1.27 [1.15–1.40] for ACS and 1.23 [1.12–1.35] for CCS) remained significantly associated with ACD. However, receiver operating characteristic curve analysis for predicting ACD revealed that the predictive value of the AHEAD score was significantly higher than that of the CHADS 2 score in both ACS and CCS (Figure). A significant difference was found in the rate of ACD among patients stratified by the AHEAD score in both groups (both P &lt;0.001). Conclusions: The AHEAD score had superior predictive value for ACD compared to the CHADS 2 score in patients with CAD, irrespective of ACS or CCS.

Abstract 4122620: Triglyceride Levels Associate With Cardiovascular Risk Across the Full Range but Not Among Individuals With Mild-to-Moderate Hypertriglyceridemia

Background: Guidelines focus on individuals with triglyceride levels of 200 to 499 mg/dL (2.3 and 5.6 mmol/L), a group for whom triglyceride-lowering therapy does not convincingly decrease risk. Hypotheses and goals: We re-assessed the hypotheses that triglyceride levels across the full biological range and within this constrained range strongly associate with cardiovascular risk. Methods: We calculated multivariable adjusted hazard ratios for major cardiovascular events and death according to baseline triglyceride levels among 119,573 individuals with triglycerides across the full biological range from the Copenhagen General Population Study, among 27,757 individuals with baseline triglycerides between 200 and 499 mg/dL (2.3 and 5.6 mmol/L) from the Copenhagen General Population Study and the Women’s Health Study, and among 31,372 individuals with mild-to-moderate hypertriglyceridemia participating in the PROMINENT, REDUCE-IT, and STRENGTH randomized trials. Results: Increasing triglyceride levels across the full range were associated with increasing risk of major cardiovascular events (N=12,241) (Figure 1). In individuals with mild-to-moderate hypertriglyceridemia from the two cohorts, combined hazard ratios (95% confidence interval) for major cardiovascular events (N=3,928) from lowest to highest triglyceride quartile were 1.0 (referent), 0.95 (0.87-1.04), 1.04 (0.95-1.13), and 1.13 (1.04-1.23). In the contemporary trials of patients selected for mild-to-moderate hypertriglyceridemia, the corresponding hazard ratios for major cardiovascular events (N=4,265) from lowest to highest triglyceride quartile were 1.0 (referent), 1.01 (0.93-1.10), 1.05 (0.96-1.14), and 1.10 (1.01-1.19). In neither prospective cohorts nor trials were triglyceride levels strongly associated with risk of cardiovascular or all-cause death within the constrained range. Conclusions: Contrary to expectations, individuals with mild-to-moderate hypertriglyceridemia may not express the same magnitude of cardiovascular risk as that observed across the full range of plasma triglycerides. Future trials of triglyceride-lowering therapy may want to consider enrollment across a wider range of triglyceride levels if there is no prior history of pancreatitis.

Abstract 4136694: Impact of left ventricular support devices on myocardial and pulmonary recovery in patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation

Background: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is used to treat cardiogenic shock. However, retrograde arterial perfusion from the femoral artery can increase left ventricular (LV) afterload, resulting in LV distention which may hamper myocardial recovery and worsen pulmonary congestion. An intra-aortic balloon pump (IABP) can mitigate LV afterload, and Impella (Abiomed, Danvers, MA) can directly unload LV pressure. This study aimed to evaluate the efficacy of LV support devices during VA-ECMO in patients with cardiogenic shock. Methods: We retrospectively collected data from 213 consecutive patients treated with VA-ECMO due to cariogenic shock at our institution between January 2013 and December 2023. Patients were categorized as either receiving VA-ECMO alone or VA-ECMO with an LV support device. The LV support device was characterized as VA-ECMO with IABP or Impella. Data were analyzed for mortality, weaning from VA-ECMO, and changes in pulmonary congestion using the congestion score index (CSI), which is a semi-quantitative approach to pulmonary congestion based on a 6-zone evaluation of chest radiography, scoring each zone from 0 (no congestion) to 3 (intense pulmonary edema). Results: In this study, 95 patients received VA-ECMO alone, whereas 118 patients received an LV support device (101 VA-ECMO with IABP and 17 VA-ECMO with Impella). LV support devices improved weaning from VA-ECMO (odds ratio, 3.09 [95% confidence interval (CI), 1.75–5.55]; p&lt;0.0001) whereas there was no difference in IABP versus Impella cohorts. Compared with VA-ECMO alone, patients with VA-ECMO with an LV support device had better survival at 30 days (OR, 3.04 [95% CI, 1.73–5.43]; p&lt;0.0001). The rate of survival to discharge was better in VA-ECMO with an LV support device versus VA-ECMO alone (hazard ratio, 2.51 [95% CI, 1.72–3.65]; p&lt;0.0001). The evaluation of pulmonary congestion using the CSI revealed that congestion significantly improved in VA-ECMO with Impella (changes of CSI: 1.86 to 1.36) but not in VA-ECMO with IABP (1.80 to 1.96) and VA-ECMO alone (1.94 to 2.14). Conclusion: An LV support device may be associated with reduced mortality and increased success in weaning off VA-ECMO in patients with cardiogenic shock. Impella may be particularly effective in reducing pulmonary congestion.

Abstract 4137396: Evolution of Tricuspid Regurgitation and Clinical Outcomes in Patients with Heart Failure with Preserved Ejection Fraction: Insights from the PURSUIT-HFpEF Registry

Background: Tricuspid regurgitation (TR) is prevalent in patients with heart failure with preserved ejection fraction (HFpEF). However, due to its high vulnerability to hemodynamic loads, the long-term observation may heighten its prognostic values. Purpose: To investigate the evolution of TR and its impact on clinical outcomes in patients with HFpEF. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. A total of 1238 patients hospitalized for acute heart failure (HF) (diagnosed by using Framingham criteria) met the inclusion criteria: an LVEF ≥50% and brain natriuretic peptide level ≥100 pg/ml. After excluding patients who died within 1 year, we included 761 patients (age 82 ± 9 years; men, 45%; atrial fibrillation, 37%) whose echocardiographic data at discharge and 1 year were available. Results: At discharge, 165 patients (21.7%) had moderate to severe TR, which increased to 185 patients (24.3%) at 1 year. Patients were categorized into 4 groups based on the TR evolution: no or mild TR that remained unchanged (n = 522 [69%]), no or mild TR that worsened to moderate to severe (n = 74 [9.7%]), moderate to severe TR that improved to no or mild (n = 54 [7.1%]), and moderate to severe TR that remained unchanged (n = 111 [15%]). During a subsequent follow-up of 33 months, patients with persistent moderate to severe TR had significantly higher mortality rates than the other groups (25.7% vs. 27.0% vs. 27.8% vs. 44.1%, log-rank p &lt; 0.001). Even after adjusting for age, sex, body mass index, left atrial diameter, and left ventricular filling pressure, persistent moderate to severe TR was independently associated with subsequent mortality (hazard ratio, 2.06, 95% confidence interval 1.42-2.99, p &lt; 0.001) Conclusions: During a one-year follow-up, changes in the TR severity were not rare in patients with HFpEF. Persistent moderate to severe TR alone was associated with subsequent mortality, highlighting the need to address persistent TR to improve the prognosis.