Absolute Event Research Articles

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Novo Nordisk.

Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK clinical practice research Datalink Aurum: A reference trial (ARISTOTLE) emulation study.

Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results. Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR < 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR. Analysis of noninterventional data generated results demonstrating noninferiority of apixaban versus warfarin consistent with prespecified benchmarking criteria. Unlike in ARISTOTLE, superiority of apixaban versus warfarin was not seen, possible due to the lower proportion of Asian patients and higher proportion of patients with well-controlled warfarin compared to ARISTOTLE. This methodological template can be used to investigate treatment effects of oral anticoagulants in patient groups excluded from or underrepresented in trials and provides a framework that can be adapted to investigate treatment effects for other conditions.

The upgraded laser calibration system of the ICARUS experiment at FNAL

The calibration of the ICARUS photo-detection system employs a low power laser diode at 405 nm. The laser pulses are delivered in front of the 360 large area PMTs with a custom optical system, that has been recently upgraded to calibrate all of them in a single run, by replacing an optical switch with a custom optical splitter. The distribution of the PMTs’ signal arrival time has a distribution with a resolution better than 1 ns, thus allowing a good determination of the absolute event timing.

Effect of variability of mechanical properties on the predictive capabilities of vulnerable coronary plaques

Background and Objective:Coronary plaque rupture is a precipitating event responsible for two thirds of myocardial infarctions. Currently, the risk of plaque rupture is computed based on demographic, clinical, and image-based adverse features. However, using these features the absolute event rate per single higher-risk lesion remains low. This work studies the power of a novel framework based on biomechanical markers accounting for material uncertainty to stratify vulnerable and non-vulnerable coronary plaques. Methods:Virtual histology intravascular ultrasounds from 55 patients, 29 affected by acute coronary syndrome and 26 affected by stable angina pectoris, were included in this study. Two-dimensional vessel cross-sections for finite element modeling (10 sections per plaque) incorporating plaque structure (medial tissue, loose matrix, lipid core and calcification) were reconstructed. A Montecarlo finite element analysis was performed on each section to account for material variability on three biomechanical markers: peak plaque structural stress at diastolic and systolic pressure, and peak plaque stress difference between systolic and diastolic pressures, together with the luminal pressure. Machine learning decision tree classifiers were trained on 75% of the dataset and tested on the remaining 25% with a combination of feature selection techniques. Performance against classification trees based on geometric markers (i.e., luminal, external elastic membrane and plaque areas) was also performed. Results:Our results indicate that the plaque structural stress outperforms the classification capacity of the combined geometric markers only (0.82 vs 0.51 area under curve) when accounting for uncertainty in material parameters. Furthermore, the results suggest that the combination of the peak plaque structural stress at diastolic and systolic pressures with the maximum plaque structural stress difference between systolic and diastolic pressures together with the systolic pressure and the diastolic to systolic pressure gradient is a robust classifier for coronary plaques when the intrinsic variability in material parameters is considered (area under curve equal to [0.91–0.93]). Conclusion:In summary, our results emphasize that peak plaque structural stress in combination with the patient’s luminal pressure is a potential classifier of plaque vulnerability as it independently considers stress in all directions and incorporates total geometric and compositional features of atherosclerotic plaques.

Identifying People at High Risk for Severe Aortic Stenosis: Aortic Valve Calcium Versus Lipoprotein(a) and Low-Density Lipoprotein Cholesterol.

Aortic valve calcification (AVC), Lp(a) [lipoprotein(a)], and low-density lipoprotein cholesterol (LDL-C) are associated with severe aortic stenosis (AS). We aimed to determine which of these risk factors were most strongly associated with the risk of incident severe AS. A total of 6792 participants from the MESA study (Multi-Ethnic Study of Atherosclerosis) had computed tomography-quantified AVC, Lp(a), and LDL-C values at MESA visit 1 (2000-2002). We calculated the absolute event rate of incident adjudicated severe AS per 1000 person-years and performed multivariable adjusted Cox proportional hazards regression. The mean age was 62 years old, and 47% were women. Over a median 16.7-year follow-up, the rate of incident severe AS increased exponentially with higher AVC, regardless of Lp(a) or LDL-C values. Participants with AVC=0 had a very low rate of severe AS even with elevated Lp(a) ≥50 mg/dL (<0.1/1000 person-years) or LDL-C ≥130 mg/dL (0.1/1000 person-years). AVC >0 was strongly associated with severe AS when Lp(a) <50 mg/dL hazard ratio (HR) of 33.8 (95% CI, 16.4-70.0) or ≥50 mg/dL HR of 61.5 (95% CI, 7.7-494.2) and when LDL-C <130 mg/dL HR of 31.1 (95% CI, 14.4-67.1) or ≥130 mg/dL HR of 50.2 (95% CI, 13.2-191.9). AVC better identifies people at high risk for severe AS compared with Lp(a) or LDL-C, and people with AVC=0 have a very low long-term rate of severe AS regardless of Lp(a) or LDL-C level. These results suggest AVC should be the preferred prognostic risk marker to identify patients at high risk for severe AS, which may help inform participant selection for future trials testing novel strategies to prevent severe AS.

Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis

Background and aimsCalcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). MethodsAVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1–99, 100–299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR). ResultsOverall, 6812 participants had AVC quantified with a mean age of 62.1 years old, 52.9 % were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5 %. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in a logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95 % CI 1.04–1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95 % CI 1.14–2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors. ConclusionsAfter multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors.

All-cause mortality risks among participants in mass-participation sporting events

ObjectivesExercise transiently increases the risk for sudden death, whereas long-term exercise promotes longevity. This study assessed acute and intermediate-term mortality risks of participants in mass-participation sporting events.MethodsData of participants in...

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

The high-energy tail of energetic electron precipitation: solar wind drivers and geomagnetic responses

Compositional NOx changes caused by energetic electron precipitation (EEP) at a specific altitude and those co-dependent on vertical transport are referred to as the EEP direct and indirect effect, respectively. The direct effect of EEP at lower mesospheric and upper stratospheric altitudes is linked to the high-energy tail of EEP (≳ 300 keV). The relative importance of this direct effect on NOx, ozone, and atmospheric dynamics remains unresolved due to inadequate particle measurements and scarcity of polar mesospheric NOx observations. An accurate parameterization of the high-energy tail of EEP is, therefore, crucial. This study utilizes EEP flux data from MEPED aboard the POES/Metop satellites from 2004–2014. Data from both hemispheres (55–70° N/S) are combined in daily flux estimates. 164 peaks above the 90th percentile of the ≳ 30 keV flux are identified. These peaks are categorized into absolute E1 and E3 events representing weak and strong ≳ 300 keV responses, respectively. A subset of absolute E1 and E3 events with similar ≳ 30 keV responses is termed overlapping events. Additionally, relative E1 and E3 events are determined by the relative strength of the ≳ 300 keV response, scaled by the initial ≳ 30 keV flux. A comparison between E1 and E3 events aims to identify solar wind and geomagnetic conditions leading to high-energy EEP responses and to gain insight into the conditions that generate a high-energy tail, independent of the initial ≳ 30 keV flux level. Superposed epoch analysis of mesospheric NO density from SOFIE confirms an observable direct impact on lower mesospheric chemistry associated with the absolute E3 events. A probability assessment based on absolute events identifies specific thresholds in the solar wind-magnetosphere coupling function (epsilon) and the geomagnetic indices Kp*10 and Dst, capable of determining the occurrence or exclusion of absolute E1 and E3 events. Elevated solar wind speeds persisting in the recovery phase of a deep Dst trough appear characteristic of overlapping and relative E3 events. This study provides insight into which parameters are important for accurately modeling the high-energy tail of EEP.

(102) A Preliminary Analysis of Outcomes and Complication Rates for Patients Undergoing Inflatable Penile Prosthesis Implantation Following Intracavernosal Injection Therapy With or Without Concurrent Anticoagulation

Abstract Introduction Medications, namely antiplatelets (AP) and anticoagulation (AC), are effective at avoiding fatal vascular complications and prolonging the lives of our patients. As such, more and more men seeking treatment for erectile dysfunction (ED) also take blood thinners. This is an interaction we must better understand to provide safe, individualized care to our patients and minimize peri-operative morbidity. Currently, there is no published information on whether differences exist in the escalation of treatment for patients with erectile dysfunction and on AC. A previous study has demonstrated no statistically significant difference in complications between AC and non-AC groups while on ICI, despite there being a higher rate of absolute bleeding events for AC patients. Objective To compare outcomes and complication rates in patients undergoing IPP implantation following ICI therapy with or without concurrent anticoagulation. Methods A retrospective observational study was undertaken. Electronic patient records from January to September 2021 were reviewed. Included patients were those who had either currently or previously utilized ICI therapy for ED treatment. ICI therapy surveys and Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) questionnaire were obtained. 85 patients met the inclusion criteria; 43 concurrently using AC during ICI therapy and 42 with no AC use. Patients who were unable to completely stop their AC medications a week before surgery due to cardiovascular concerns or recommendations, underwent bridging with a shorter half life and reversible AC. Extra measures taken during the IPP for such patients, including meticulous hemostasis, compression dressing and drain insertion. Additional data regarding IPP implantation as well as any complications or infections experienced following IPP surgery which were compared between the AC and no AC groups. Results Patient demographics, IPP implantation information and subsequent complication rates are listed below in Table 1. There was no statistically significant difference in the rate of patients who underwent IPP placement between the AC and no AC cohorts. Moreover, there was also no statistically significant difference in median time from date of initial ICI usage to time of IPP placement as well as median time from IPP placement to last follow-up. Among the 12 total patients who underwent IPP placement, none experienced any complications, including infection, mechanical failure, device removal or revision at any time point up to last follow-up (longest was 18 months). No statistically significant differences in EDITS score between both groups was observed. Conclusions These preliminary findings, while requiring large-scale follow up, show that there is no statistically significant difference in rate of patients opting for IPP surgery following initiation of ICI therapy regardless of concomitant AC usage as well as the rate of complications following IPP implantation. Lastly, there is no drawbacks in performing such procedure in this specific cohort of patients, provided that all necessary measures are taken into consideration to minimize bleeding complications. Disclosure No.

(390) A Preliminary Analysis of Outcomes and Complication Rates for Patients Undergoing Inflatable Penile Prosthesis Implantation following Intracavernosal Injection Therapy With or Without Concurrent Anticoagulation

Abstract Introduction Medications, namely antiplatelets (AP) and anticoagulation (AC), are effective at avoiding fatal vascular complications and prolonging the lives of our patients. As such, more and more men seeking treatment for erectile dysfunction (ED) also take blood thinners. This is an interaction we must better understand to provide safe, individualized care to our patients and minimize peri-operative morbidity. Currently, there is no published information on whether differences exist in the escalation of treatment for patients with erectile dysfunction and on AC. A previous study has demonstrated no statistically significant difference in complications between AC and non-AC groups while on ICI, despite there being a higher rate of absolute bleeding events for AC patients. Objective To compare outcomes and complication rates in patients undergoing IPP implantation following ICI therapy with or without concurrent anticoagulation. Methods A retrospective observational study was undertaken. Electronic patient records from January to September 2021 were reviewed. Included patients were those who had either currently or previously utilized ICI therapy for ED treatment. ICI therapy surveys and Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) questionnaire were obtained. 85 patients met the inclusion criteria; 43 concurrently using AC during ICI therapy and 42 with no AC use. Patients who were unable to completely stop their AC medications a week before surgery due to cardiovascular concerns or recommendations, underwent bridging with a shorter half life and reversible AC. Extra measures taken during the IPP for such patients, including meticulous hemostasis, compression dressing and drain insertion. Additional data regarding IPP implantation as well as any complications or infections experienced following IPP surgery which were compared between the AC and no AC groups. Results Patient demographics, IPP implantation information and subsequent complication rates are listed below in Table 1. There was no statistically significant difference in the rate of patients who underwent IPP placement between the AC and no AC cohorts. Moreover, there was also no statistically significant difference in median time from date of initial ICI usage to time of IPP placement as well as median time from IPP placement to last follow-up. Among the 12 total patients who underwent IPP placement, none experienced any complications, including infection, mechanical failure, device removal or revision at any time point up to last follow-up (longest was 18 months). No statistically significant differences in EDITS score between both groups was observed. Conclusions These preliminary findings, while requiring large-scale follow up, show that there is no statistically significant difference in rate of patients opting for IPP surgery following initiation of ICI therapy regardless of concomitant AC usage as well as the rate of complications following IPP implantation. Lastly, there is no drawbacks in performing such procedure in this specific cohort of patients, provided that all necessary measures are taken into consideration to minimize bleeding complications. Disclosure No.

Âge vasculaire et risque cardiovasculaire chez les patients hypertendus suivis à l'institut de cardiologie d'Abidjan

ObjectiveTo calculate the vascular age of hypertensive patients and assess the risk at 10 years of occurrence of an absolute cardiovascular event in outpatient consultation of the Abidjan Heart Institute. Patients and methodology: Cross-sectional study with descriptive and analytical purposes from June 2021 to September 2021, i.e. 4 months in patients at least 30 years of age followed in the outpatient department for arterial hypertension without cardiovascular complications. Data were collected using a questionnaire. We considered the parameters established in the D'Agostino chart for the calculation of vascular age. Each parameter was weighted and the total points obtained corresponded to the vascular age. The cardiovascular risk at 10 years was also obtained from another abacus established by D'Agostino by cross-referencing the total points of each patient with pre-established data. ResultsThree hundred hypertensive people were included in this study. The calendar average age was 62.0 ± 10 years with extremes of 30 and 95 years. The gender distribution showed female predominance and there was no significant difference in vascular age by sex. The mean vascular age of all patients was 73.4 ± 9.9 years. The mean difference between actual and vascular age was 11.4 years. Dyslipidemia (p = 0.0002), diabetes (p = 0.0004) and unstandardized BP (p = 0.0000) significantly influenced vascular age. There was no significant difference between smokers and non-smokers (p = 0.1349). All men had a greater than 30% risk of having a cardiovascular accident while women before the age of 35 had no risk. Over the age of 60, almost all patients (both men and women) had a greater than 30% risk of having a cardiovascular accident at 10 years. ConclusionThe calculation of vascular age made it possible to assess arterial aging and calculate the probability at 10 years of occurrence of a cardiovascular event. This study also highlights the importance of cardiovascular risk and vascular age assessment for management adaptation and therapeutic education.

Memeplex-based memetic algorithm for the multi-objective optimal design of composite structures

Hybrid construction is proposed to decrease costs in lightweight structures using fiber-reinforced plastics (FRP) composite materials. Minimum weight, minimum strain energy (stiffness), and minimum energy variability of the structural system response are the objectives of the robust design optimization approach applied to composite shell structures with stiffeners. The trade-off depends on given stress, displacement, and buckling constraints imposed on composite structures considering non-linear geometric behavior. The design variables are ply angles and ply thicknesses of shell laminates, the cross-section dimensions of stiffeners, and the variables related to the selection of materials and their distribution at the laminate level and subsequently of the laminates along the structure. A Multi-Objective Memetic Algorithm (MOMA) applies multiple learning procedures exploring the synergy of different cultural transmission rules. An enlarged virtual population with a dual age-dominance nature captures and updates the Pareto curve. The concept of memeplex controls the meme selection and their propagation along the hybrid genetic and cultural evolution path. The success of memetic learning procedures is analyzed by measuring each meme's relative and absolute success events according to different approaches, depending on the reference time used in evolutionary history. Results show that MOMA is promising in multi-objective optimization of composite hybrid structures.

Differences in risk stratification for worsening heart failure in patient with reduced versus preserved ejection fraction using diagnostic parameters available in implantable cardiac monitors

Abstract Background Ambulatory management of heart failure (HF) patients require the ability to identify when patients are at highest risk of impending HF events (HFE). The risk stratification ability based on diagnostic parameters measured by implantable cardiac monitors may differ depending on the left ventricular ejection fraction (LVEF) of HF patients. Objective The purpose of this study was to evaluate the difference in risk stratification performance of individual diagnostic parameters currently available in ICMs in identifying patients at increasing risk of HFE in patients with reduced versus preserved LVEF. Methods Patients with history of HFE who were implanted with an ICM was identified from the aggregated and de-identified electronic health record (EHR) database during 2007-2021. The device collected data were merged with the EHR data to create a de-identified database of real-world patients. Currently approved ICMs measure nighttime heart rate (NHR), heart rate variability (HRV), atrial fibrillation (AF) burden, ventricular rate during AF, and activity duration (ACT) daily and stores and transmits this information for the lifetime of the device. Each diagnostic parameter was categorized into high, medium, or low risk using a combination of features predefined in earlier studies. HFEs were defined as inpatient stay with a primary diagnosis of HF or HF related observation unit or emergency visit with IV diuresis administration. Patients were divided into two cohorts of patients with (1) median LVEF ≤ 40% (HFrEF), and (2) median LVEF &amp;gt; 40% (HFpEF). Performance evaluation was performed by simulating monthly follow-ups which consisted of looking at the individual parameter risk states in the last 30 days and evaluating the occurrence of HF events in the following 30 days. A marginal Cox proportional hazards model was used to compare HF events for different risk groups (high, medium, and low) for each individual diagnostic parameter. Results There was a total of 267 patients with median LVEF ≤ 40% (64±13 years old, 67% male) and 622 patients with LVEF&amp;gt;40% (69 ±12 years old, 47% male). For the reduced LVEF cohort, there was a total of 4,867 follow-up months with 65 monthly evaluations (1.3%) had an HF event in the next 30 days. For the preserved LVEF cohort, there was a total of 11,057 follow-up months with 224 monthly evaluations (2.0%) had an HF event in the next 30 days. The event rate comparisons between the risk groups for each individual diagnostic parameter are shown in Figure. As compared to ICM patients with HFrEF, ICM patients with HFpEF had higher absolute event rate across all risk groups, thus lowering the relative risk stratification between risk groups. Conclusion ICM patients with HFpEF showed a higher event rate and hence a higher absolute risk for each risk group, however relative risk between risk groups and hence the risk stratification performance for identifying risk for worsening HF was better in patients with HFrEF.

Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I2 = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I2 = 0%; low-certainty evidence). Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.

Abstract 11975: The Multi-Ethnic Association of Aortic Valve Calcium and Long-Term Risk of Incident Severe Aortic Stenosis: Multi-Ethnic Study of Atherosclerosis

Introduction: Racial/ethnic differences exist in the prevalence and burden of aortic valve calcium (AVC) and in the incidence of aortic stenosis (AS). While AVC is strongly associated with the long-term risk for AS, whether this association differs by race/ethnicity remains uncertain. Hypothesis: There will be a similar absolute event rate for incident moderate to severe AS within AVC categories across race/ethnicity. Methods: 6,812 MESA participants underwent non-contrast EKG gated CT at MESA Visit 1 and AVC was quantified using the Agatston scoring method. Adjudication of incident moderate and severe AS was defined using standard clinical criteria. We assessed the association of AVC with the combined outcome of incident moderate-severe AS stratified by race/ethnicity. We calculated the event rate per 1,000 person-years and multivariate Cox proportional hazards with log-transformed AVC as a continuous variable. Results: The mean age was 62 years old and 47% of participants were women. Over a median follow-up of 16.7 years, there were 140 participants diagnosed with moderate AS (n=56) and severe AS (n=84). The prevalence of AVC &gt;0 by race was 15.8% for White, 13.3% for Hispanic, 12.3% for Black, and 8.3% for Chinese participants. The rate of incident moderate-severe AS was similar across race/ethnicity when stratified by AVC, p for interaction=0.62 (Figure 1). Log-transformed AVC had a similar association with the long-term risk of moderate-severe AS regardless of race/ethnicity: White HR 1.83 (95% CI 1.63-2.05), Hispanic: HR 2.12 (95% CI 1.79-2.51), Black: HR 2.31 (95% CI 1.79-2.98), and Chinese: HR 2.14 (95% CI 1.30-4.41). Conclusions: The association between AVC and moderate-severe AS was similar across race/ethnicity. This suggests that previously observed differences in AS by race/ethnicity may be predominantly due to the differing prevalence of AVC.

Direct oral anticoagulants versus vitamin K antagonist after transcatheter aortic valve implantation

ObjectiveAfter transcatheter aortic valve implantation (TAVI), the optimal regimen of anticoagulant therapy in patients with an additional indication for oral anticoagulation remains a matter of debate. This study investigates the...

(128) Complication Rates in Patients Using Intracavernosal Injection Therapy for Erectile Dysfunction With or Without Concurrent Anticoagulant Use—A Single-Center, Retrospective Pilot Study

Abstract Introduction Intracavernosal injection therapy (ICI) is an effective intervention used to treat erectile dysfunction (ED). It has been proposed that caution should be exercised when prescribing ICI to patients currently taking anticoagulants (AC) due to the theoretical increased risk of bleeding, however, there is limited literature describing complication rates of actively anticoagulated patients utilizing ICI. Objective We sought to determine whether there was a difference in bleeding and other complications in a cohort of patients using ICI therapy with or without concurrent AC use. Methods We reviewed our institutional electronic health record and identified 168 patients who were seen in our clinic from January to August 2020 who had either currently or previously utilized ICI therapy for ED treatment. These patients were surveyed regarding their ICI therapy as well as given the Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) questionnaire. Data from 85 patients was obtained; 43 concurrently using AC during ICI therapy and 42 with no AC use. Documented bleeding events (e.g. bruising, hematoma), complications, and mean EDITS scores were compared between the two groups. Fisher’s exact test for categorical variables and a two-tailed t-test were used with p&amp;lt;0.05 considered to be significant. Results There were more absolute bleeding complications in the AC group versus the no AC group, with 3/43 AC patients (7%, 95% CI: 2.4-18.6) and 0/42 no AC patients (0%, 95% CI: 0-8.4) experiencing some type of bleeding complication on ICI. However, there was no statistically significant difference found in overall or stratified documented bleeding events and complications between the two groups. Conclusions Findings from a single-center cohort of patients suggest that ICI therapy may be a safe and effective treatment modality for ED in patients with concurrent anticoagulant usage, however, given the higher rate of absolute bleeding events in our AC cohort, future assessment in a higher-powered study is warranted in determining a more accurate estimation of risk or propensity for bleeding complications in patients on AC using ICI therapy. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Run Wang, MD, FACS is a consultant for Boston Scientific and Teleflex.

Prognostic impact of artificial intelligence-based fully automated global circumferential strain in patients undergoing stress CMR.

To determine whether fully automated artificial intelligence-based global circumferential strain (GCS) assessed during vasodilator stress cardiovascular (CV) magnetic resonance (CMR) can provide incremental prognostic value. Between 2016 and 2018, a longitudinal study included all consecutive patients with abnormal stress CMR defined by the presence of inducible ischaemia and/or late gadolinium enhancement. Control subjects with normal stress CMR were selected using a propensity score-matching. Stress-GCS was assessed using a fully automatic machine-learning algorithm based on featured-tracking imaging from short-axis cine images. The primary outcome was the occurrence of major adverse clinical events (MACE) defined as CV mortality or nonfatal myocardial infarction. Cox regressions evaluated the association between stress-GCS and the primary outcome after adjustment for traditional prognosticators. In 2152 patients [66 ± 12 years, 77% men, 1:1 matched patients (1076 with normal and 1076 with abnormal CMR)], stress-GCS was associated with MACE [median follow-up 5.2 (4.8-5.5) years] after adjustment for risk factors in the propensity-matched population [adjusted hazard ratio (HR), 1.12 (95% CI, 1.06-1.18)], and patients with normal CMR [adjusted HR, 1.35 (95% CI, 1.19-1.53), both P < 0.001], but not in patients with abnormal CMR (P = 0.058). In patients with normal CMR, an increased stress-GCS showed the best improvement in model discrimination and reclassification above traditional and stress CMR findings (C-statistic improvement: 0.14; NRI = 0.430; IDI = 0.089, all P < 0.001; LR-test P < 0.001). Stress-GCS is not a predictor of MACE in patients with ischaemia, but has an incremental prognostic value in those with a normal CMR although the absolute event rate remains low.

Predicting risk of AF in ischaemic stroke using sinus rhythm ECG abnormalities: A meta-analysis.

To identify ECG changes in sinus rhythm that may be used to predict subsequent development of new AF. We identified prospective and retrospective cohort or case control studies evaluating ECG patterns from a 12-lead ECG in sinus rhythm taken in hospital or community predicting subsequent development of new AF. For each identified ECG predictor, we then identify absolute event rates and pooled risk ratios (RR) using an aggregate level random effects meta-analysis. We identified 609,496 patients from 22 studies. ECG patterns included P wave terminal force V1 (PTFV1), interatrial block (IAB) and advanced interatrial block (aIAB), abnormal P wave axis (aPWA), PR prolongation and atrial premature complexes (APCs). Pooled risk ratios reached significance for each of these; PTFV1 RR 1.48 (95% CI 1.04-2.10), IAB 2.54 (95% CI 1.64-3.93), aIAB 4.05 (95% CI 2.64-6.22), aPWA 1.89 (95% CI 1.25-2.85), PR prolongation 2.22 (95% CI 1.27-3.87) and APCs 3.71 (95% CI 2.23-6.16). Diabetes reduced the predictive value of PR prolongation. APC and aIAB were most predictive of AF, while IAB, PR prolongation, PTFV1 and aPWA were also significantly associated with development of AF. These support their use in a screening tool to identify at risk cohorts who may benefit from further investigation, or following stroke, with empirical anticoagulation.