Primary Endpoint Research Articles

OGC SO12 - Extended Venous Thromboembolism Prophylaxis in Postoperative Oesophagogastric Cancer Patients: A Completed Audit

Abstract Background Venous thromboembolism (VTE) is a life-threatening complication for cancer patients undergoing oesophagogastric surgery. The NICE recommends extending pharmacological VTE prophylaxis to 28 days for patients undergoing major abdominal cancer surgery. While the effectiveness of in-hospital VTE prophylaxis is well-documented, the optimal duration for postoperative VTE prophylaxis remains a subject of debate. This study aims to evaluate the prescribing compliance, effectiveness, and safety of extending VTE prophylaxis to 28 days following hospital discharge (HD), a policy adopted trust-wide since 2014. Method This is an 11-year retrospective study from July 2012-2022, followed by a complete audit cycle conducted between January 2023-2024. The study included all patients who underwent cardio-esophagectomy or gastrectomy for oesophagogastric cancers. Exclusion criteria comprised patients who died during the index admission, those who underwent benign oesophagogastric surgery or local excision of gastrointestinal stromal tumours (GIST), and patients with peripherally inserted central catheter (PICC) line-associated VTE. The primary outcome measured was the prescribing compliance of 28-day VTE prophylaxis post-hospital discharge. Secondary endpoints included the incidence of VTE and bleeding complications necessitating hospital readmission within 28 days of discharge. Results Our study included 582 patients, showing that post-2014, 423 out of 490 patients (86.3%) were discharged with 28-day VTE prophylaxis, compared to 13 out of 92 patients (14.1%) pre-2014, indicating a significant improvement (p<0.05). Only one patient (0.17%) developed VTE more than 28 days post-discharge, and no readmissions due to bleeding complications. In the subsequent audit, 63 out of 68 patients (92.6%) received the prophylaxis, further increasing prescribing compliance. Comparing the two periods, compliance improved from 86.3% to 92.6%, though not statistically significant (p=0.145). Overall, VTE incidence was minimised from 0.17% to 0%, with no readmissions due to bleeding complications. Conclusion Routine extended VTE prophylaxis for 28 days post-hospital discharge should be recommended for cancer patients undergoing oesophagogastric surgery. This practice has significantly improved prescribing compliance rates, reduced post-hospital discharge VTE incidence, and demonstrated safety, with no hospital readmissions due to bleeding complications.

Open-label, controlled, phase 2 clinical trial assessing the safety, efficacy, and pharmacokinetics of INM004 in pediatric patients with Shiga toxin-producing Escherichia coli–associated hemolytic uremic syndrome

Abstract Background Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in the pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study is aimed at assessing the safety, pharmacokinetics, and efficacy of INM004 in pediatric patients with STEC-HUS. Methods Phase 2, open-label clinical trial with an historical control arm. Patients in the treatment arm received two doses of INM004. The primary endpoints were the safety profile, pharmacokinetics, and efficacy (dialysis days) of INM004. Secondary endpoints included other kidney and extrarenal outcomes. Propensity score matching was used for efficacy comparisons between arms. Results Fifty-seven and 125 patients were enrolled in the treatment and control arm, respectively. After propensity score matching, 52 patients remained in each arm. INM004 was well-tolerated. Eight adverse events were considered possibly related, none of which were serious or severe. In the primary efficacy endpoint, patients of the treatment arm presented a non-statistically significant difference of two dialysis days. On secondary endpoints, non-statistically significant trends toward fewer patients needing dialysis and dialysis for more than 10 days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm. Conclusions INM004 showed an adequate safety profile. Efficacy non-statistically significant trends suggesting a beneficial effect in the amelioration of kidney injury were observed. These results encourage the conduction of a phase 3 study of INM004 in pediatric patients with STEC-HUS. Graphical Abstract

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p<0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Abstract 4138269: The Association Between Automatically Assessed Broad P-wave and Cardiovascular Events in Patients with Cardiovascular Risks

Background: A broad P wave in electrocardiography reflects atrial remodeling and is associated with cardiovascular events. Although there are several reports on the association between a broad P wave and cardiovascular events, the association between automatically assessed P-wave duration and cardiovascular events in cardiovascular high-risk patients has not been clarified. Hypothesis: We hypothesized that a greater automatically assessed P-wave duration would be associated with cardiovascular events in patients with cardiovascular risk factors. Methods: We included 4,654 patients with access to automated electrocardiography (ECG) analysis of those in the Cardiovascular Prognostic Coupling Study in Japan (a registry of subjects with one or more cardiovascular risk factors, excluding patients with atrial fibrillation). Twelve-lead ECG was conducted, and the P-wave duration in each lead was analyzed automatically using the 12-lead ECG Analysis system (Fukuda Denshi, Tokyo). We selected the maximum P wave duration (Pmax) among the 12 leads. The primary endpoint was a composite endpoint (cardiovascular death, nonfatal myocardial infarction/stroke), and the secondary endpoint was heart failure hospitalization. We assessed two P-wave cut-offs (Pmax ≥ 140, 150 msec) in relation to cardiovascular events. Results: There were 218 patients with Pmax ≥140 ms and 123 patients with Pmax ≥150 ms. N-Terminal pro brain natriuretic peptide (NT-proBNP) was significantly higher in patients with Pmax ≥140 ms than in those with Pmax <140 ms (median 134.0 vs. 65.7 pg/mL, p<0.001). NT-ProBNP was also higher in patients with Pmax ≥150 ms than in those with Pmax <150 ms (median 192.0 vs. 66.9 pg/mL, p<0.001). The mean follow-up period was 53 ± 17 months. The primary endpoint occurred in 180 cases and the secondary endpoint in 73 cases. A broad P-wave defined as Pmax ≥140 ms was independently associated with the primary endpoint (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.04–2.70, p=0.034) but not with the secondary endpoint (HR 1.96, 95% CI 0.99–3.90, p=0.055) after adjustment for covariates including NT-proBNP. A broad P-wave defined as Pmax ≥150 ms was independently associated with both the primary endpoint (HR 2.08, 95% CI 1.06–4.09, p=0.034) and the secondary endpoint (HR 3.22, 95% CI 1.38–7.52, p=0.007). Conclusions: Automatically assessed P-wave duration of Pmax ≥ 150 ms was a significant predictor of cardiovascular events and heart failure.

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.

Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial

AbstractPancreatic ductal adenocarcinoma (PDA) is characterized by low cytotoxic lymphocytes, abundant immune-suppressive cells, and resistance to immune checkpoint inhibitors (ICI). Preclinical PDA models showed the HDAC inhibitor entinostat reduced myeloid cell immunosuppression, sensitizing tumors to ICI therapy. This phase II study combined entinostat with nivolumab (PD1 inhibitor) in patients with advanced PDA (NCT03250273). Patients received entinostat 5 mg orally once weekly for 14-day lead-in, followed by entinostat and nivolumab. The primary endpoint was the objective response rate (ORR) by RECIST v1.1. Secondary endpoints included safety, duration of response, progression free-survival and overall survival. Between November 2017 and November 2020, 27 evaluable patients were enrolled. Three showed partial responses (11% ORR, 95% CI, 2.4%-29.2%) with a median response duration of 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were, respectively, 1.89 (95% CI, 1.381-2.301) and 2.729 (95% CI, 1.841-5.622) months. Grade ≥3 treatment-related adverse events occurred in 19 patients (63%), including decreased lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. As exploratory analysis, peripheral and tumor immune profiles changes were assessed using CyTOF, mIHC, and RNA-seq. Entinostat increased dendritic cell activation and maturation. Gene expression analysis revealed an enrichment in inflammatory response pathways with combination treatment. Although the primary endpoint was not met, entinostat and nivolumab showed durable responses in a small subset of PDA patients. Myeloid cell immunomodulation supported the preclinical hypothesis, providing a basis for future combinatorial therapies to enhance clinical benefits in PDA.

Abstract 4135708: Obesity and the risk of cardiac death in coronary artery disease

Background: The prevalence of obesity is increasing worldwide reaching epidemic proportions. Obesity increases the risk of coronary artery disease (CAD), but there is little prospective evidence about the effect of obesity on the risk of cardiac death in CAD patients. Aim: We aimed to investigate the effect of obesity and the risk of cardiac death in a prospective cohort of CAD patients. Methods: We have prospectively enrolled 1,946 patients with CAD (mean age 66.9±8.6, 68% male), with a mean follow-up of 8.7±2.2 years. BMI was measured at baseline and was categorized into 4 groups: 1) BMI 18.5-24.9 kg/m 2 (normal weight, reference group), 2) BMI 25-29.9 kg/m 2 (overweight), 3) BMI 30-34.9 kg/m 2 (class 1 obesity), and 4) BMI >35 kg/m 2 (class 2 obesity). The primary endpoint was cardiac death and secondary endpoints were sudden cardiac death/arrest (SCD/SCA), non-sudden cardiac death, non-cardiac death, and heart failure (HF) hospitalization. Statistical analysis was performed with Cox regression and was adjusted for age, sex, type 2 diabetes, CCS class, kidney function (eGFR), systolic and diastolic blood pressure, LDL, smoking, SYNTAX score, and left ventricle ejection fraction. Results: The prevalence of BMI 18.5-24.9 kg/m 2 was 18.5% (n=359), BMI 25-29.9 kg/m 2 was 47.8% (n=929), BMI 30-34.9 kg/m 2 was 24.0% (n=466), and BMI>35 kg/m 2 was 9.7% (n=189). During the follow-up, cardiac death occurred in 156 subjects, SCD/SCA in 75 subjects, non-sudden cardiac death in 81 subjects, and non-cardiac death in 197 subjects. BMI >35 kg/m 2 was associated with an increased trend of cardiac death (adjusted HR 1.92, 95% CI 0.92-4.01; p=0.08) and an increased risk of non-sudden cardiac death (adjusted HR 4.11, 95% CI 1.58-10.68; p=0.004) and HF hospitalization (adjusted HR 2.83, 95% CI 1.06-7-54; p=0.04), but not with SCD/SCA (adjusted HR 0.79, 95% CI 0.24-2.56; p=0.69) or noncardiac death (adjusted HR 0.85, 95% CI 0.43-1.69; p=0.64). The risk of cardiac death or secondary endpoints was not increased in patients with overweight or class 1 obesity. Conclusions: Class 2 obesity was associated with an increased risk of non-sudden cardiac death and heart failure hospitalization among CAD patients. Obesity may have adverse long-term effects on cardiac function and prognosis among CAD patients, supporting the benefit of optimal weight control therapy.

Abstract 4141442: The Feasibility and Adherence of Online Intensive Cardiac Rehabilitation Program for Coronary Artery Disease-A pilot Study

Introduction/Background: Remote cardiac rehabilitation is becoming more popular, but most are exercise-based cardiac rehabilitation programs, and online intensive cardiac rehabilitation (ICR) programs that include not only exercise training but also dietary guidance, stress management, and group support have not been widespread. Research Questions/Hypothesis: Whether high adherence and improvement of CAD risk factors demonstrated for the online ICR program. Goals/Aims: We assessed the program adherence by participation rate as the primary endpoint and physical findings, typical CAD risks and nutritional indices as the secondary endpoint. Methods/Approach: The J-ICR program provides online instruction using Zoom (San Jose, CA: Zoom Video Communications Inc.). The program consisted of four parts: aerobic exercise training, dietary education for the Japan diet, stress management training through mindfulness, and group support (10 participants per group) for 3 hours per session, once a week for 12 weeks (36 hours total). Twenty-two patients were enrolled and adherence to the program was examined. Changes in CAD risk factors were also analyzed. Results/Data: After excluding 3 patients who withdrew consent before the program, the current study population consisted of 19 male participants. The mean age was 66 years old, 95% had hypertension, 37% had diabetes mellites and all had hyperlipidemia. Eight patients had myocardial infarction and 15 cases of angina pectoris. The average participation rate of the program was 90.2% and there was no drop out during the program. As the secondary endpoint, body weight （69.2kg vs. 68.2kg; p=0.02), systolic and diastolic blood pressure (126.8mmHg vs. 121.4mmHg; p<0.01 and 79.5mmHg vs. 77.6mmHg; p=0.18), LDL cholesterol (78.9mg/dl vs 77.6mg/dl; p=0.68), HbA1c (6.3% vs. 6.4%; p=0.39), and amount of sodium intake (9.5 g/day vs. 9.5g/day; p=0.68) and total energy intake (2,137kcal/day vs. 2,076kcal/day; p=0.25). Conclusion: The J-ICR program is feasible and may yield improvements in CAD risk factors such as body weight and systolic blood pressure. Since this is a pilot study to explore the feasibility of the online J-ICR, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers.

Direct Aspiration Versus Combined Technique for Anterior Distal, Medium Vessel Occlusions Stroke: The JET Distal Vessel Occlusion Study

BACKGROUND AND OBJECTIVES: The optimal mechanical thrombectomy technique for distal, medium vessel occlusion (DMVO) stroke remains unknown. We aimed to compare the safety and efficacy of 2 thrombectomy first-line approaches, direct aspiration (DA), and combined technique (CT) in patients with DMVOs. METHODS: We conducted a retrospective review of a prospectively collected multicenter database of patients with DMVOs (at or distal to M2 and A1), who underwent mechanical thrombectomy with JET D reperfusion catheters between January 2020 and December 2021. The primary end point was the rate of first-pass complete recanalization, defined as modified treatment in cerebral infarction (mTICI) 3. The hemorrhagic complications, the 90 days functional independence rate (modified Rankin Scale 0-2), and mortality were also evaluated. RESULTS: A total of 171 consecutive patients were enrolled (95 in DA and 76 in CT cohort). The 2 groups had comparable demographics and baseline characteristics. The DA group had a higher rate of first-pass effect (40.0% vs 10.5%, P < .001), final mTICI 2b-3 (89.5% vs 71.1%, P = .003) and final mTICI 3 (58.9% vs 28.9%, P < .001), shorter groin to reperfusion time (65 ± 43 min vs 101 ± 60 min, P < .001), and higher rate of 90-day functional independence (63.7% vs 36.1%; P = .001) compared with the CT group. There were no significant differences in hemorrhagic complications between the 2 groups. The DA group showed a lower rate of 90-day mortality (9.9% vs 27.8%; P = .004). CONCLUSION: In patients with DMVOs, DA with a distal dedicated reperfusion catheter appears to demonstrate better safety and efficacy when compared with the CT using the same catheter.

A phase 4, multicenter, global clinical study to evaluate discontinuation and rechallenge of pexidartinib in patients with tenosynovial giant cell tumor previously treated with pexidartinib

AbstractBackgroundPexidartinib is effective in patients with tenosynovial giant cell tumor (TGCT) for whom surgery is not feasible. Durability of response after discontinuation of pexidartinib and the safety and efficacy of restarting pexidartinib have not been previously recorded. This phase 4 study was designed to mimic the real‐world experience with pexidartinib to evaluate the effects of discontinuation of and retreatment with pexidartinib in patients with TGCT who previously benefited from the drug.MethodsThis was a global, multicenter, phase 4 study that enrolled patients with TGCT who were experiencing clinical benefit from pexidartinib in one of four prior phase 1 or phase 3 studies investigating pexidartinib in the disease. Patients could choose to continue pexidartinib at the same dose (the treatment‐continuation cohort) or discontinue treatment with the option to restart pexidartinib (the treatment‐free/retreatment cohort). Tumor progression determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, patient‐reported outcomes (the Patient‐Reported Outcomes Measurement Information System–Physical Function [PROMIS‐PF] questionnaire and the EuroQol 5‐dimension, 5‐level [EQ‐5D‐5L] visual analog scale), and safety were assessed every 3 months. The primary end point was the proportion of patients in the treatment‐free/retreatment cohort who remained treatment‐free at month 12 and 24; this did not depend on disease progression.ResultsThirty‐two patients were enrolled: 21 chose to enter the treatment‐continuation cohort, and 11 entered the treatment‐free/retreatment cohort. During the treatment‐free period, six of 11 (54.5%) patients in the treatment‐free/retreatment cohort had progressive disease (PD) according to RECIST, version 1.1, whereas no patient in the treatment‐continuation cohort had disease progression. Over the 24‐month study, three of 11 (27.3%) patients in the treatment‐free/retreatment cohort restarted treatment because of RECIST version 1.1 PD, symptomatic progression, or both (n = 1 each). The probability of remaining treatment‐free in the treatment‐free/retreatment cohort was 73% (95% confidence interval, 37%–90%). In the treatment‐free/retreatment cohort, the median progression‐free survival of the treatment‐free period was 22.8 months (95% confidence interval, 1.6 months to not estimable). By 6 months of retreatment, all retreated patients achieved new disease stabilization with no new safety concerns; two patients had clinically significant improvements in PROMIS‐PF and EQ‐5D‐5L visual analog scale scores. The mean PROMIS‐PF and EQ‐5D‐5L scores remained stable throughout the study. There was no hepatotoxicity and no new safety signal in either cohort.ConclusionsIn this small phase 4 study designed to evaluate outcomes in patients who stopped and restarted pexidartinib, 54.5% of patients who discontinued pexidartinib showed PD, with a median progression‐free survival of 22.8 months. Each of the three patients who restarted pexidartinib stopped progressing, and some reported a new gain in physical function. No PD was detected in patients who remained on treatment, and the safety profile did not indicate long‐term hepatotoxicity or any new safety concerns.Plain Language Summary Pexidartinib is a medication for people with tenosynovial giant cell tumor (TGCT) for whom surgery is not recommended. This study examined what happens when patients stop taking pexidartinib (after it has helped them) to see whether it is safe and effective to restart if needed. Thirty‐two patients were followed for 2 years: 21 chose to continue pexidartinib and did not experience disease progression, while 11 chose to stop pexidartinib; 54.5% of them had disease progression within 2 years. Three patients who stopped pexidartinib restarted treatment after their tumor size increased or their symptoms worsened. Restarting pexidartinib was safe and effective in these patients.

Abstract 4135434: Effect of early nutritional guidance for patients with acute myocardial infarction: A single center retrospective cohort study

Introduction/Background: Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis. Research Question: There remains a lack of evidence regarding the impact of early nutritionist-led dietary guidance on the prognosis of AMI patients. Aim: This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods/Approach: A retrospective cohort study enrolling 409 AMI patients who underwent emergency percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results/Data: During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance during hospitalization. The multivariate Cox regression model revealed early nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Furthermore, undernourished patients, defined as those with a geriatric nutritional risk index of 98 or less, showed a similar prognosis to those with good nutritional status after receiving nutritional guidance, indicating that nutritional guidance improves prognosis. Conclusion: Nutritionist-led dietary guidance for patients with AMI can potentially improve total mortality and is expected to be more effective in undernourished patients. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Abstract 4115645: NLRP3 Inflammasome Inhibition With Dapansutrile in Type 2 Diabetes and Elevated Systemic Inflammation: Rationale and Design of the DAPAN-DIA study

Background: Monoclonal antibodies against IL-1β decrease inflammation, improve insulin secretion and glycaemia, and reduce residual CV risk, but must be injected and are associated with higher incidence of fatal infection. There remains an unmet need for an oral treatment for T2D patients at risk for cardiometabolic complications to safely reduce IL-1β-mediated inflammation chronically&with low risk of immunosuppression. In an initial dose-range finding study in heart failure patients with T2D, we reported evidence of anti-hyperglycaemic efficacy and improvement in LVEF with dapansutrile an oral specific inhibitor of the NLRP3 inflammasome. Objectives: To investigate the potential of preventing the transition to organ complications, The EU funded consortium INTERCEPT-T2D in collaboration with US based biotech Olatec Therapeutics has launched a clinical trial of anti-inflammatory therapy with dapansutrile targeting T2D patients with low-grade inflammation. Methods: Dapansutrile in Diabetes and Complications (DAPAN-DIA, NCT06047262) aims to determine whether NLRP3 inhibition with dapansutrile has the potential to not only improve glycaemia but also reduce micro- and macro-vascular risk and complications from diabetes. DAPAN-DIA is a multicenter, pbo-controlled, prospective, randomized, double-blind trial conducted in Switzerland, France, Belgium and Germany. A total of 300 patients with T2D, HbA1c >7.5% and hsCRP>1.5 mg/L are being randomized to either dapansutrile 1000 mg BID or matching PBO tablets for 6 months (2:1 ratio dapansutrile: pbo). The primary endpoint is change from baseline HbA1c. Secondary endpoints include biomarkers associated with diabetic complications, progression of MASLD as well as chronic inflammation (IL-1 β, IL-6 and hsCRP). A subject-assessed QoL questionnaire is also collected. To detect an absolute difference of 0.5% in HbA1c between groups, approximately 300 subjects will be randomized 2:1 ratio to achieve 80% power, assuming a standard deviation of 1.2% in change from baseline in HbA1c at week 26. Results: The trial has launched and currently is enrolling subjects. Conclusions: DAPAN-DIA is the first placebo-controlled, adequately powered, large, multi-center study with an oral NLRP3-specific Inhibitor, dapansutrile. The trial will generate important data on a new clinically relevant dimension in T2D care where consideration at diagnosis of inflammatory parameters are of importance for the transition to T2D-related complications.

A Randomized Pilot Trial of Virtual Reality Surgical Planning for Head and Neck Oncologic Resection

ObjectiveApplication of virtual reality (VR) for surgical planning may improve clinical outcomes for head and neck cancer (HNC) resection. There is a lack of randomized trials and meaningful metrics to assess such technological applications. Our objective was to evaluate the feasibility of a VR protocol for oncologic surgical planning and assess the impact on surgical outcomes.MethodsA randomized controlled trial utilizing a VR Case Enhancement Protocol (VRCEP) versus standard of care (SOC) surgical planning was conducted. The primary endpoint was feasibility, defined as >80% successful VRCEPs. Metrics included surgeon task‐load burden (TLB) using the NASA Task‐Load Index and “margin events,” defined as "the need for defect‐driven margins, positive frozen margins, and/or positive final margins." Margin events were used to calculate a margin event score (MES) per case and margin event rate (MER) per cohort.ResultsThirty‐four patients were included in the final analysis (17 VRCEP, 17 SOC) with 94.4% of eligible VRCEP cases completed (17/18). Surgeon TLB was unchanged with VRCEP. Cases undergoing VRCEP were associated with a lower mean MES (0.27 vs. 0.94, p = 0.014) and MER (11.6% vs. 35.6%, p = 0.0041). VRCEP was associated with decreased defect‐driven margins (10% vs. 53.3%, p = 0.032). Although not statistically significant, positive frozen and final margin rates were lower in VRCEP.ConclusionCompletion of the VRCEP was feasible with no significant increase in surgeon TLB appreciated. VRCEP yielded fewer MEs. Further investigation into the benefit of VR in HNC resection is warranted. Margin events may represent useful metrics for assessing novel surgical technologies.Level of Evidence2 Laryngoscope, 2024

Abstract 4137854: Effect of Sacubitril/valsartan on Left Ventricular Tissue Characterization in Heart Failure with Left Ventricular Ejection Fraction Below 50%

Background: The effects of sacubitril/valsartan (ARNI) on myocardial tissue characterization in heart failure (HF) with left ventricular ejection fraction (LVEF) <50% are still unclear. Objective: The present study investigated the effects of 9 months of ARNI treatment on LV structure and myocardial tissue characteristics in HF with LVEF <50% using cardiac magnetic resonance (CMR). Methods: This study was a prospective, 2-arm, randomized, open-label clinical trial (SAVE-HF). Sixty-four HF outpatients with LVEF<50% were randomized 1:1 from ACE inhibitor/ARB to ARNI (ARNI group) or control group (continued ACE inhibitor/ARB). CMR was performed to evaluate LV structure and tissue characteristics, including changes in LV extracellular volume fraction (delta ECV) before and after the 9-month period. The primary endpoint was difference in ECV between the two groups. Secondary endpoints included changes in LV volumes and mass, LVEF, extracellular mass (ECM) calculated as LV mass times ECV/100, and intracellular mass (ICM) calculated as LV mass minus ECM. Results: A total of 59 of 64 stable patients (68±12 years; 52 men) completed the 9-month intervention followed by repeated CMR. ARNI decreased systolic BP levels from the first month by approximately 10 mmHg. ARNI group exhibited significant reductions in LV end-diastolic and end-systolic volumes and LV mass. While LVEF and ECV remained unchanged (31.6±5.0 vs. 31.9±5.0%, p=0.26), both ECM and ICM significantly decreased after ARNI. In the control group, systolic BP, LV volumes and LV mass, ECV, ECM and ICM were unchanged. Comparing the two groups, while delta ECV was not significantly different, delta ECM was greater in ARNI group than control group (-3.6±7.3 vs. 0.2±5.3 g, p=0.025), indicating improved LV tissue characteristics. Conclusions: ARNI reduced LV volume and LV mass, accompanied with reduction of both ECM and ICM, and consequently unchanged ECV. These findings may suggest that ARNI may improve LV tissue characteristics and protect from LV remodeling in HF patients with their LVEF<50%.

Abstract 4140167: Lipid Management among US Veterans with Prevalent Atherosclerotic Cardiovascular Disease (ASCVD) * Veteran Affairs Lipid Optimization Reimagined Quality Improvement Program (VALOR-QI)

ASCVD is the most prevalent form of cardiovascular disease and the main cause of morbidity and mortality for Veterans in the VA healthcare system. Management of cholesterol is one of the most effective approaches for reducing CV disease, however, over two-thirds of Veterans with ASCVD are not optimally managed. Veterans with ASCVD are at high risk for recurrent CV events and can benefit greatly from more effective management of their low-density lipoprotein (LDL-C) cholesterol. The reasons for the current undertreatment of dyslipidemia in Veterans with ASCVD are multifaceted, including factors such as low disease awareness among the patients, patient’s preference, statin intolerance, and poor adherence to medications. Purpose: VALOR-QI is a collaborative effort between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting Veterans’ cardiovascular health. Method: This project targets at risk veterans over 18 years of age, with ASCVD and LDL-C ≥70 mg/dl or non-HDL-C ≥100 mg/dl identified across 50 VA medical centers nationwide. As part of the program, VA sites work with an AHA QI Consultant to develop and deploy a local quality improvement plan to help overcome site specific barriers preventing Veterans from achieving optimal cholesterol levels. Health coaches at these centers aid in lipid optimization through patient counseling, medication adherence support, appointment reminders, and referrals to a nutritionist or clinical pharmacist as required. The plan’s effectiveness will be assessed by tracking LDL-C goal achievement rates, LDL-C changes with therapy use, and veteran demographics. Our primary endpoints are for over 30% of veterans to reach the LDL-C target and a significant drop (around 10%) from baseline in veterans with ASCVD and LDL-C not at target. Best practices are shared among sites using the PDSA implementation science model. Results: As of May 2024, 182 patients at the Hines VA are engaged in the project. Among them, 84.8% are on lipid-lowering therapy, 83.1% are on statins (with 57.9% on a high intensity dose), and 11.3% are on dual therapy with a statin plus an additional medication (PCSK9 inhibitor or ezetimibe). So far, 59.5% of enrolled patients reached their LDL-C cholesterol target of <70 mg/dl. Conclusion: Lipid lowering strategies with collaboration of patients, network providers, dieticians and health coaches improved lipid control in veterans with ASCVD.

Abstract 4120229: Shift in body mass index category and associated cardiometabolic risk factors: a post hoc analysis from the SURMOUNT-4 trial

Background: In SURMOUNT-4, participants with obesity demonstrated a mean weight reduction of 21% during the 36-week lead-in with the maximum tolerated dose (MTD) of tirzepatide (TZP). During the 52-week double-blind period, participants who switched to placebo (PBO) experienced a 14% weight regain, while those who continued TZP achieved an additional 6% weight reduction. This post hoc analysis assessed whether participants who shifted to a lower BMI category had improved cardiometabolic factors. Methods: Shift in BMI category (<25 kg/m 2 , 25 to <30 kg/m 2 , 30 to <35 kg/m 2 , 35 to <40 kg/m 2 , and ≥40 kg/m 2 ) from baseline (week 0) during the lead-in period (week 36) and at the primary endpoint (week 88) and from week 36 to week 88 was assessed in participants from SURMOUNT-4 randomized to TZP MTD (N=332) or PBO (N=329). BMI shifts were grouped into “improved” (shift to ≥1 lower category) or “not improved” (stable/attenuated [no change/shift to a higher category]). Changes from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, vitals and lipid profile were assessed. Results: From weeks 0 to 36, 296 (89%) participants improved in BMI category with TZP, and none had attenuated (Table). From weeks 36 to 88, 130 (39%) participants improved in BMI category with TZP, while the majority (99%) randomized to PBO did not. Overall, from weeks 0 to 88, 304 (92%) vs 189 (57%) participants improved in BMI category with TZP vs PBO, respectively, where the improvements observed in the PBO group originated from the 36-week lead-in period. In general, participants who improved in BMI category at week 88 were noted to have greater improvements in cardiometabolic parameters with TZP vs PBO, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, triglycerides, and cholesterol (total, non-HDL-c, LDL-c, and VLDL-c). Conclusions: In this post hoc analysis of SURMOUNT-4, the majority of TZP-treated participants shifted to lower “improved” BMI categories. Shift to an improved BMI category was accompanied by improved cardiometabolic risk factors, suggesting that TZP treatment may lower further cardiovascular outcomes. Relevant outcomes trials are ongoing.

Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL > 70 or non-HDL > 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI > LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p < 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect < 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.

Abstract 4138248: Outcomes of Patients with Radiation-Associated Cardiac Disease Undergoing Cardiothoracic Surgery: Development of a Disease Specific Risk Score

Background: Radiation-associated cardiac disease (RACD) has significant long-term mortality and morbidity, often requiring cardiac surgery(CS). Hypothesis: We sought to study factors associated with longer-term survival in RACD patients and develop a specific risk score associated with 5-year survival following CS. Methods: This was an observational cohort study of 351 patients with documented RACD (252 [72%] had mantle radiation for lymphoma at a mean of 18 years prior), who underwent CS at a tertiary care center between 1991-2018. Clinical characteristics were collected, and Society of Thoracic Surgeons (STS) score was calculated. The primary endpoint was mortality. Multivariable analysis for 5-year mortality was performed using age, sex, history of lymphoma, New York Heart Association class, prior cardiac surgery, atrial fibrillation, constriction, chronic pulmonary disease, serum creatinine, left ventricular ejection fraction, right ventricular systolic pressure and valvular surgery(aortic, mitral or tricuspid). Results: Clinical characteristics are shown in Figure 1. Mean follow-up was 6.2±4.6 years&5-year mortality occurred in 123 (35%) patients (7 [2%] in-hospital deaths). Cox 5-year survival analysis results are shown in Figure 2A. A receiver operator curve analysis for 5-year mortality showed an area under curve of 0.70 (95% confidence interval 0.64-76, p<0.001). Subsequently, a 5-year risk score (0-7 points) was generated (Figure 2 A); with an increasing risk of mortality at 5 years, based on increasing risk score (Figure 2C). Cardiac reoperation was not associated with worse outcomes. Conclusion: RACD patients undergoing CTS have a high rate of 5-year mortality, despite a low baseline STS score&perioperative mortality. A novel RACD-specific risk score (incorporating higher age, abnormal renal/pulmonary, constrictive pericarditis&need for concomitant mitral valve surgery) provides good discrimination for 5-year survival&could be used for shared-decision making.

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<0.09) and low left ventricular ejection fraction (26 vs. 29, p<0.09), and significantly reduced rate of angiotensin converting enzyme inhibitors or angiotensin receptor blockers (30% vs. 70%, p<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<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<0.05) and mortality (33% vs. 18%, log-rank p<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<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.

Abstract 4137855: Hybrid Coronary Revascularization versus Traditional Coronary Artery Bypass Grafting for Left Main Disease

Background: The current guideline-recommended intervention for left main (LM) disease is coronary artery bypass grafting (CABG). Hybrid coronary revascularization (HCR) combines robotic coronary artery bypass and percutaneous coronary intervention (PCI) and offers a less invasive approach for patients with LM and multivessel coronary artery disease. We aim to compare clinical outcomes at 30 days, 6 months and 1 year between HCR and CABG in patients with LM disease. Methods: We retrospectively screened 761 patients who underwent bypass for LM disease between 2019 and 2023 at a single institution. A total of 118 patients who underwent either HCR (n=59) or CABG (n=59) were included after propensity matching for baseline characteristics. The primary endpoint was major adverse cardiovascular events (MACE), defined as death, myocardial infarction, repeat revascularization and stroke, at 30 days, 6 months and 1 year, which was assessed using chi-squared tests. Secondary outcomes are individual components of MACE at 30 days, 6 months and 1 year. Kaplan-Meier curves were used to visualize the difference in 1-year cumulative MACE-free survival across groups coupled with a log-rank test. Results: The mean age was 68.93±11 years for HCR patients and 68.41±10.11 years for CABG patients (p=0.394). SYNTAX score was high (> 33) for 49.1% of HCR patients and 67.3% of CABG patients (p=0.15). Hospital length of stay was shorter for HCR compared to CABG (4.07 ± 1.21 days vs. 7.58 ± 7.71 days, p<0.001). MACE events were significantly lower in the HCR group at 30 days (0% vs 10.2%; p=0.01), 6 months (0% vs 17%; p=0.002) and 1 year (2.4% vs 20.5%; p=0.01). The cumulative MACE-free survival at 1 year was significantly higher in the HCR group (p=0.007). There were no significant differences in secondary outcomes at any time point with the exception of lower repeat revascularization at 6 months in the HCR group (0% vs 10.9%; p=0.02). Conclusion: This retrospective study demonstrates that HCR is a viable alternative to CABG for LM disease. While randomized clinical trial data is still needed, this less invasive approach is a promising treatment strategy for patients with high surgical risk.