Contemporary Risk Research Articles

Metabonomic Biomarkers of Plaque Burden and Instability in Patients With Coronary Atherosclerotic Disease After Moderate Lipid-Lowering Therapy.

Contemporary risk assessment in patients with coronary atherosclerotic disease (CAD) often relies on invasive angiography. However, we aimed to explore the potential of metabolomic biomarkers in reflecting residual risk in patients with CAD after moderate lipid-lowering therapy. We analyzed serum metabolomic profile among 2560 patients with newly diagnosed CAD undergoing moderate lipid-lowering therapy, through nuclear magnetic resonance spectroscopy and quantified 175 metabolites, predominantly lipoproteins and their components. CAD severity was evaluated using Gensini score for plaque burden and circulating cardiac troponin T levels for plaque instability. The association of metabolites with CAD severity was examined using multivariate linear regression, and the underlying potential causality was explored using a 2-sample Mendelian randomization approach. Two composite metabolomic indices were constructed to reflect CAD severity using least absolute shrinkage and selection operator linear regression, and their associations with risk of major adverse cardiac events during a median follow-up of 3.8 years were evaluated using Cox models. Our investigation revealed that triglycerides and apolipoprotein B in low-density lipoprotein particles displayed stronger associations with CAD severity compared with the clinically used low-density lipoprotein cholesterol marker. In large high-density lipoprotein, components like cholesterol, cholesterol esters, triglyceride, apolipoprotein A1/A2 showed inverse associations with CAD severity. Certain metabolites, including apolipoprotein B and dihydrothymine, showed a putative causal link with Gensini score. Notably, per standard deviation increase in Gensini score-based metabolomic index was associated with 14.8% higher major adverse cardiac event risk (hazard ratio, 1.148 [95% CI, 1.018-1.295]) independent of demographic factors, medication use, and disease status. Our findings highlight the potential of nuclear magnetic resonance-based metabolomics in identifying novel biomarkers of plaque burden and instability. Metabolites related to plaque burden may facilitate noninvasive assessment of CAD prognosis.

Assessing the Accuracy of Cardiovascular Disease Prediction Using Female-Specific Risk Factors in Women Aged 45 to 69 Years in the UK Biobank Study.

Cardiovascular disease (CVD) is the leading cause of mortality in women. We aimed to assess whether adding female-specific risk factors to traditional factors could improve CVD risk prediction. We used a cohort of women from the UK Biobank Study aged 45 to 69 years, free of CVD at baseline (2006-2010) followed until the end of 2019. We developed Cox proportional hazards models using the risk factors included in 3 contemporary CVD risk calculators: Pooled Cohort Equation - Atherosclerotic Cardiovascular Disease, Qrisk2, and PREDICT. We added each of the following female-specific risk factors, individually and all together, to determine if these improved measures of discrimination and calibration for predicting CVD: early menarche (<11 years), endometriosis, excessive, frequent or irregular menstruation, miscarriage, number of miscarriages, number of stillbirths, infertility, preeclampsia or eclampsia, gestational diabetes (without subsequent type 2 diabetes), premature menopause (<40 years), early menopause (<45 years), and natural or surgical early menopause (menopause <45 years or timing of menopause reported as unknown and oophorectomy reported at age <45). In the model of 135 142 women (mean age, 57.5 years; SD, 6.8) using risk factors from Pooled Cohort Equation - Atherosclerotic Cardiovascular Disease, CVD incidence was 5.3 per 1000 person-years. The c-indices for the Pooled Cohort Equation - Atherosclerotic Cardiovascular Disease, Qrisk2, and PREDICT models were 0.710, 0.713, and 0.718, respectively. Adding each of the female-specific risk factors did not improve the c-index, the net reclassification index, the integrated discrimination index, the slope of the regression line for predicted versus observed events, and the Brier score or plots of calibration. Adding all female-specific risk factors simultaneously increased the c-index for the Pooled Cohort Equation - Atherosclerotic Cardiovascular Disease, Qrisk2, and PREDICT models to 0.712, 0.715, and 0.720, respectively. Although several female-specific factors have been shown to be early indicators of CVD risk, these factors should not be used to reclassify risk in women aged 45 to 69 years when considering whether to commence a blood pressure or lipid-lowering medication.

A contemporary simple risk score for prediction of severe acute kidney injury after heart transplantation.

The aim of this study was to develop a simple risk score to estimate severe acute kidney injury (AKI) risk based on a large contemporary heart transplantation (HT) cohort. From 1 January 2015 to 31 December 2021, all consecutive HT recipients in our institute were included and analysed for the occurrence of AKI within the first seven postoperative days. Patients transplanted between 2015 and 2019 comprised the derivation cohort, and those transplanted between 2020 and 2021 formed the validation cohort. The primary endpoint was severe AKI (AKI stages 2-3). The impact of severe AKI on 90day mortality was also evaluated. Overall, 430 HT patients were included in the derivation cohort, and 108 were included in the validation cohort. Postoperative AKI occurred in 388 (72%) patients, including 162 (30%) severe AKI. The risk of 90day mortality significantly increased in patients with severe-AKI. Seven independent predictors of severe AKI were found in the derivation cohort, including recipients' body mass index, history of diabetes, anaemia, preoperative inotropes, estimated glomerular filtration rate, cardiopulmonary bypass duration and intraoperative red blood cell transfusion. The occurrence of severe AKI increased gradually from the lowest to the highest of the four risk score groups in the derivation and validation cohort. The scoring prediction model showed a highly acceptable discriminating power for severe-AKI [C statistic: 0.76, 95% confidence interval (CI): 0.71-0.80 for derivation cohort; C statistic: 0.79, 95% CI: 0.71-0.89 for validation cohort]. A contemporary simple risk score based on available variables from patients undergoing HT can accurately discriminate the risk of severe AKI.

Abstract 4143289: Contemporary and Genomic Cardiovascular Risk Factors Have Explanatory Power Similar to Traditional Risk Factors for Incident Myocardial Infarction

Background: Modifiable cardiovascular risk factors (CRF) have been proposed to be responsible for 80-90% of the risk for incident coronary artery disease (CAD). However, these studies were conducted prior to the era of preventive medications, novel biomarkers, and genetic risk scores. The relative contributions of traditional and contemporary CRF in light of secular trends in worsening cardiometabolic health globally have not been assessed. Hypothesis: Including genetic risk scores and contemporary biomarkers will enhance discrimination and explainability of myocardial infarction (MI) incidence prediction. Methods: The UKBiobank was used to identify traditional CRF (hypertension, diabetes, dyslipidemia, smoking, waist-to-hip ratio (WHR), diet, exercise, alcohol intake and socioeconomic deprivation), and contemporary/genetic CRF (lipoprotein(a), high-sensitivity C-reactive protein [hsCRP], familial hypercholesterolemia [FH] variants, and polygenic risk score for CAD [PRS CAD ]). Incident MI was defined as first-time MI diagnosis or coronary revascularization. Base model discrimination was assessed using C-statistics from Cox proportional hazards models. Percent contribution of each risk factor was calculated by explanatory power lost via Nagelkerke R 2 after removal of the CRF from the full model. Population attributable risks (PAR) were additionally assessed for each model and CRF individually. Results: Over a median [IQR] follow-up of 11.0 [9.6, 12.5] years, 17409/299707 (5.8%) of participants developed incident CAD. C-statistics sequentially increased from base model to traditional CRF to contemporary/genetic CRF model with PAR of 84.3% (95% CI 82.4%-86.5%) ( Table 1 ). Among CRFs, hypertension (C 0.74, R 2 loss 15.2%, PAR 32.5%) and PRS CAD (C 0.72, R 2 loss 12.4%, PAR 38.4%) most strongly explained MI incidence by all 3 indices. Based on discriminability, ApoB:ApoA1 ratio (C 0.71, R 2 loss 3.4%), presence of diabetes (C 0.71, R 2 loss 2.2%), and log(hsCRP) (C 0.71, R 2 loss 1.82%) were subsequently prioritized. PAR analyses included prevalence in prioritization where WHR, presence of diabetes, and log(lipoprotein(a)) levels rose higher. Conclusions: The addition of genetic risk factors and contemporary biomarkers to explanatory models for CAD shows previously underappreciated importance of contemporary CRFs such as PRS, hsCRP, and lipoprotein(a) alongside traditional CRFs such as hypertension, dyslipidemia and presence of diabetes.

Evolving Transparent Credit Risk Models: A Symbolic Regression Approach Using Genetic Programming

Credit scoring is a cornerstone of financial risk management, enabling financial institutions to assess the likelihood of loan default. However, widely recognized contemporary credit risk metrics, like FICO (Fair Isaac Corporation) or Vantage scores, remain proprietary and inaccessible to the public. This study aims to devise an alternative credit scoring metric that mirrors the FICO score, using an extensive dataset from Lending Club. The challenge lies in the limited available insights into both the precise analytical formula and the comprehensive suite of credit-specific attributes integral to the FICO score’s calculation. Our proposed metric leverages basic information provided by potential borrowers, eliminating the need for extensive historical credit data. We aim to articulate this credit risk metric in a closed analytical form with variable complexity. To achieve this, we employ a symbolic regression method anchored in genetic programming (GP). Here, the Occam’s razor principle guides evolutionary bias toward simpler, more interpretable models. To ascertain our method’s efficacy, we juxtapose the approximation capabilities of GP-based symbolic regression with established machine learning regression models, such as Gaussian Support Vector Machines (GSVMs), Multilayer Perceptrons (MLPs), Regression Trees, and Radial Basis Function Networks (RBFNs). Our experiments indicate that GP-based symbolic regression offers accuracy comparable to these benchmark methodologies. Moreover, the resultant analytical model offers invaluable insights into credit risk evaluation mechanisms, enabling stakeholders to make informed credit risk assessments. This study contributes to the growing demand for transparent machine learning models by demonstrating the value of interpretable, data-driven credit scoring models.

Left ventricular dysfunction, pulmonary congestion, or both and cardiovascular risk after acute myocardial infarction

Abstract Background Patients with acute myocardial infarction (AMI) complicated by left ventricular systolic dysfunction (LVSD), pulmonary congestion, or both are at increased risk for adverse cardiovascular events, including long-term heart failure. The EMPACT-MI trial studied the efficacy and safety of early initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in this population. We set out to evaluate the contemporary real-world risk associated with AMI presenting with LVSD and/or congestion and the projected impact of implementing early SGLT2i post-MI across the spectrum of risk. Purpose To evaluate the independent risk of presenting with LVSD, congestion, or both in patients with AMI. We will further explore the potential impact of the implementation of early initiation of SGLT2i in real-world clinical practice. Methods We conducted a retrospective population-based cohort study in Ontario, Canada, analyzing AMI hospitalizations from April 2009 to March 2022, emulating the EMPACT-MI trial cohort. Patients that survived to hospital discharge were stratified by baseline presentation with LVSD (defined as LVEF&amp;lt;50%), signs or symptoms of congestion or both and compared with a referent group without either risk factor (none). Exclusion criteria were previously established heart failure, prior SGLT2i use, eGFR &amp;lt; 20 ml/min/1.73m2 or chronic dialysis. The primary outcome was a composite of HF hospitalization or all-cause mortality at 30 days and 1 year. We used a multivariable logistic regression model to report an odds ratio (OR) and 95% confidence intervals (CI) adjusted for clinical risk factors. Results Among 36,837 AMI patients, 3% presented with congestion, 55% with LVSD, 10% with both, and 32% with none. Age/sex-adjusted 30-day event rates for the primary endpoint were 30%, 22%, 57%, and 7%, respectively. The corresponding adjusted ORs were 3.34 (95% CI: 2.05-5.46) for congestion, 3.58 (95% CI: 2.72-4.71) for LVSD, and 7.01 (95% CI: 5.09-9.65) for both, versus the reference group (none) (Figure 1). At year 1, a similar pattern of risk was observed (Figure 2). Based on the results of the EMPACT-MI trial being reported at the ACC conference in April 2024, relative and absolute risk differences in outcomes with implementation of early initiation of SGLT2i post-MI in real-world clinical practice across the spectrum of presentation will be reported. Conclusion Patients presenting with pulmonary congestion and/or LVSD remain at high risk of adverse cardiovascular events following AMI. This high-risk group represents an unmet need with a potential impact for improvement with novel interventions such as SGLT2i.

Cardiovascular disease risk in people with diabetes in the era of universal diabetes screening

Abstract Background/Introduction Traditionally, most people with diabetes have been considered at high cardiovascular disease (CVD) risk and CVD preventive treatment has been recommended for almost all patients after diagnosis. However, guidelines are increasingly recommending a more stratified approach to preventive treatment informed by predicted CVD risk. In the early 2000’s, New Zealand initiated the world-first national diabetes screening programme, as a component of a national CVD risk assessment programme, and by 2016, approximately 90% of eligible New Zealand adults had been screened. We hypothesised that in the era of universal diabetes screening, many recently diagnosed patients will be at low CVD risk and that contemporary CVD risk prediction equations would be required to accurately assess their risk. Purpose We aimed to develop sex-specific 5-year CVD risk prediction models in people with diabetes in New Zealand using a contemporary natural-population based cohort, and to characterise the distribution of CVD risk. Methods De-identified individual-level linkage of multiple health administrative datasets was undertaken to establish a cohort of almost all adults with diabetes in the northern region of New Zealand (one-third of the national population), without CVD or heart failure, and aged 30–74 years on January 1, 2014, with follow-up linkage to hospitalisations and mortality until December 31, 2018. Sex-specific models were developed to estimate the 5-year risk of CVD hospitalisation or death, with 15 pre-defined predictors, including sociodemographic variables, diabetes-related and renal function measures. Results 64,645 participants (median age: 57 years [IQR: 49–65]) were included in the final cohort, of whom 4,992 had first CVD events during 301,272 person-years follow-up. Models calibrated well in both women and men (Figure 1). Overall, increasing age; high deprivation level; smoking-related hospitalisations or use of smoking cessation medications; history of atrial fibrillation; high levels of haemoglobin A1c, total cholesterol to HDL cholesterol ratio, and albumin-to-creatinine ratio; use of blood pressure-lowering medications and insulin were associated with elevated CVD risk. Median 5-year CVD risks were 4.9% (IQR: 2.9%–8.1%) in women and 7.7% (4.8%–12.0%) in men. There was a wide range of predicted 5-year CVD risk, with 51% of women and 27% of men having a predicted risk below 5%, and 6% of women and 16% of men having a risk of 15% or above (Figure 2). Conclusions This study demonstrated marked heterogeneity in predicted CVD risk in people with diabetes in an era of universal diabetes screening. As diabetes screening is increasingly undertaken as part of a routine CVD risk assessment, these findings will have important clinical implications for accurately targeting new but expensive CVD preventive medications to the highest risk patients.

Coronary inflammation stratifies risk in patients undergoing coronary CT angiography: the Oxford Risk Factors and Non-Invasive Imaging (ORFAN) study

Abstract Background Patients with chest pain symptoms often undergo coronary CT angiography (CCTA) for the diagnosis of obstructive coronary artery disease (CAD) to guide revascularisation. However, acute cardiac events could occur in the absence of obstructive CAD. Further risk stratification of patients could potentially be useful by quantifying coronary inflammation using the Fat Attenuation Index (FAI) Score, and an artificial intelligence (AI)-assisted prognostic model that captures the inflammatory risk by integrating CCTA-derived metrics (including FAI Score and plaque burden) and the patient’s clinical risk factors. Purpose To evaluate the risk of cardiac events among patients without obstructive CAD, and the prognostic value of integrating coronary inflammation in risk stratifying this patient group. Methods From the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, patients undergoing CCTA in 7 UK Hospitals (n=40,091) were followed up for the incidence of cardiac mortality over a median(IQR) of 2.7(1.4-5.3) years. In a nested cohort of 3,393 patients with long-term follow up, we evaluated the long-term prognostic value of FAI Score and the performance of AI-Risk algorithm over a median(IQR) follow up of 7.7(6.4-9.1) years. Reclassification of risk category from AI-Risk was compared with contemporary clinical risk score (QRISK3). Results Patients without obstructive CAD (n=32,533, 81.1%) accounted for 63.7% of all cardiac deaths (n=1,754) during follow up, highlighting the substantial proportion of cardiac events in absolute terms given a large proportion of patients without obstructive CAD. In the nested cohort with long-term follow up, FAI Score in any of the 3 epicardial coronary arteries was significantly associated with cardiac mortality with or without obstructive CAD. In the whole cohort, the highest quartile of FAI Score in LAD showed 20-times higher risk of cardiac death compared with the lowest quartile (Panel A). Integrating coronary inflammation with clinical risk factors and plaque burden, patients with very-high AI-Risk classification showed 6-fold higher risk of cardiac mortality compared to low/medium risk, with good alignment of the incident predicted events from AI-Risk and observed events. (Panel B) The predicted cardiac mortality from AI-Risk also demonstrated good calibration with the observed events in the whole population. (Panel C) Finally, AI-Risk significantly reclassify the risk above clinical risk factor-based prediction (QRISK3) (Panel D). Conclusion Patients with high coronary inflammation measured by FAI Score showed significantly elevated risk for cardiac mortality. The AI-enabled absolute risk prediction algorithm leads to significant reclassification of patients undergoing routine CCTA, and can be used as a precision medicine tool.

Reduction of aortic stiffness in newly diagnosed persons with HIV-infection: modifiable vascular dysfunction after antiretroviral therapy?

Abstract Background People living with HIV (PLWH) are at an increased risk of cardiovascular disease (CVD), which is underestimated by contemporary risk stratification systems[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD. Aortic stiffness, as measured with pulse wave velocity (PWV), is a validated predictor of CVD [2,3] and has been shown to be elevated in PLWH at the time of HIV diagnosis compared to HIV-uninfected persons[4]. Purpose To prospectively assess the influence of contemporary antiretroviral therapy (ART) on aortic stiffness in a group of newly diagnosed PLWH in a low- to middle-income setting. Methods A group of ART naïve PLWH with modest cardiovascular risk and free from known CVD, was recruited at the time of HIV diagnosis from the Western Cape Province of South Africa. Aortic stiffness was measured using carotid-femoral PWV on a commercially available device that simultaneously measured the carotid and femoral waveforms on a supine patient in a temperature-controlled room utilising established methodology[4]. The algorithmically-calculated time delay between the upstroke of the carotid and femoral wave-forms provided the transit time (TT). Carotid femoral path distance (path length) was measured using surface anatomy. PWV was calculated as direct path length divided by TT. Aortic distensibility was expressed according to the Bramwell-Hill equation as 3.57/PWV(squared)[5]. ART was initiated and PWV was re-evaluated 9 months later. Results Seventy-three participants completed follow-up and were included. The cohort was relatively young (mean age 32±7 years) with good female representation (n=33, 45%). Most received tenofovir/lamivudine/dolutegravir (n=71, 97%) Half of the group smoked cigarettes. Two participants were controlled hypertensives, and two participants had metabolic syndrome. A significant decrease in PWV (with scaling factor of 0.8) was observed at 9 months of ART (5.93 ±1.0 vs. 5.69 ±1.0 m/s; p=0.01). Aortic distensibility increased significantly as well (0.20 [IQR: 0.16 to 0.26] vs. 0.21 [IQR: 0.19 to 0.27] mmHg-1; p=0.02). Conclusion Improvement in aortic stiffness was observed in a group of newly diagnosed PLWH after 9 months of ART-initiation. This provides evidence of a modifiable component of vascular dysfunction and, in turn, cardiovascular risk with the use of contemporary ART at 9 months. It is unknown if this effect will be sustained long-term. The use of aortic stiffness (alone or in combination with other parameters) as a predictor of cardiovascular outcomes in the ART era requires further study.Abstract figureAbstract table

Effectiveness of contemporary risk stratification in patients with hypertrophic cardiomyopathy: a pilot study

Abstract Introduction Risk stratification and primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM) is a challenging discipline. When using current stratification systems, there is always a compromise between sensitivity and specificity. Objective In our pilot study, we sought to determine the incidence of SCD and the effectiveness of stratification systems, i.e., the ESC HCM Risk-SCD score and the system of individual major risk factors (RF) according to ACC/AHA in patients followed in an expert center. Methods Patients with HCM were risk-stratified and followed for 10 ± 8 years at the referral HCM center. Results Five hundred and five patients were stratified, and 71 (14%) were implanted with a cardioverter-defibrillator (ICD) based on risk stratification. ICD patients were stratified at age 39 ± 17 years, of which 26 (35%) were women, maximal left ventricular wall thickness (MLWT) was 23 ± 7 mm, and left atrial dimension (LA) 46 ± 7 mm. During follow-up, 12 (17%) patients had ≥ 1 appropriate ICD therapy at age 46 ± 19 years. Patients with ≥ 1 appropriate ICD therapy had an average 5-year ESC score of 1.8 ± 0.4% and an average ACC/AHA major RF of 1.4 ± 0.8, MLWT 25 ± 6 mm, LA 47 ± 7 mm. None of the ICD patients died of SCD. Five (7%) patients suffered from ICD complications, including 4 (6%) inappropriate shock, and one patient experienced infective endocarditis requiring system extraction. During follow-up, 118 (23%) patients died, of which 28 (6%) from HCM-related causes, 12 (2%) from stroke, 11 (2%) from advanced heart failure, one perioperatively (myectomy) and 4 (1%) patients died suddenly (SCD). The mean age of SCD patients at the time of stratification was 59 ± 14 years; all were male, MLWT 18 ± 5 mm, LA 49 ± 2 mm, mean ESC score 2.0 ± 0.9%, and three (75%) had no RF present according to ACC/AHA. The ESC HCM Risk-SCD score was markedly less sensitive (sensitivity 56%; 95% CI 21-86) but more specific (specificity 98%; 95% CI 96-99) than the ACC/AHA approach (sensitivity 77%; 95% CI 46-95; and specificity 71%; 95% CI 67-75) (Figure). Conclusion With current risk stratification, albeit imperfect, SCD is rare in HCM patients managed at an expert center.

The ultimate political question? Realism and omnicide

ABSTRACT Realist political theory purports to prioritize the goals of order, security, and ‘political survival’. In spite of these concerns, it has not yet addressed the growing risk that humanity might be lurching towards self-extinction. This contribution considers what omnicidal risk means for contemporary realism, making two arguments. First, we argue that omnicidal risk poses a political problem in a distinctly realist sense of the term. In doing so, we demonstrate that omnicide is a relevant concern for all realists, while ordorealists in particular hold an unrecognized commitment to mitigating omnicidal risk. Second, by demonstrating the extent to which capitalism can be considered a cause of contemporary omnicidal risk, we argue that this concern and commitment should draw realists – and, in particular, ordorealists – into a critique of contemporary political economy. Realism should not ignore omnicidal risk; instead, its consideration should work to radicalize realism.

Surgical Closure of Ventricular Septal Defect: Contemporary Results and Risk Factors for Electrophysiological Changes

Abstract Background The surgical closure of a ventricular septal defect is a commonly performed procedure. Postoperative ECG changes are common findings that needs a proper assessment to provide valuable insights into the outcomes of the patients. In this study, we investigate the potential risk factors associated with electrophysiological changes following surgical closure of ventricular septal defects. Methodology A Prospective, non-randomized study was conducted from October 2020 to December 2022 on patients scheduled for VSD closure. Patients with prior abnormal Congenital electrophysiological disturbances, Internal pacemaker, Ebstein's anomaly, associated sub-aortic membrane or Hypertrophic obstructive cardiomyopathy, Iatrogenic VSD, need Aortic root dilatation with VSD closure were excluded. 12-lead ECG was reported on ICU admission and daily thereafter till discharge. Various demographic and peri-operative data were recorded and its correlation to the presence of electrophysiological changes and final outcomes were analyzed. Results 200 patients who underwent surgical VSD closure were included. Arrhythmias occurred in 41 patients (20,5%). The encountered arrhythmias were sinus bradycardia with junctional escape in 24 patients, junctional ectopic tachycardia in 10 patients, supraventricular tachycardia in 2 patients, premature complex in 2 patients, 2nd degree heart block in 4 patients and 3rd degree block in 2 patients. Mother's hypertension, preoperative mechanical ventilation, Associated cardiac anomalies, Down syndrome, size of VSD, type of VSD, Total bypass time, Aortic cross clamp time, Concomitant procedures, Intra operative pacing, and residual VSD, were identified in a univariate analysis as Risk factors for occurrence of arrhythmias. The multivariate logistic regression analysis shows that the most significant risk factors for the occurrence of ECG changes were outlet VSD type, mitral valve repair as a concomitant procedure and aortic cross clamp time &amp;gt;45 minutes. Conclusion Surgical VSD closure is a safe procedure with low mortality and morbidity rates. Younger age and lower body weight are risk factors for prolonged hospitalization, intensive care unit stay and mechanical ventilation. Longer crossclamp and CPB times were significant predictors of post Op ECG changes and associated complications with prolonged ICU and hospital stay.

Embolic Ischemic Cortical Stroke in a Young Flight Instructor with a Small Patent Foramen Ovale

BACKGROUND: Stroke in young patients is frequently associated with a patent foramen ovale (PFO). Controversy exists over whether the PFO is a cause, a risk factor, or an incidental finding. Estimating the individualized risk of stroke recurrence has been difficult to ascertain. This has implications for aeromedical certification for pilots following stroke recovery. CASE REPORT: A 28-yr-old male flight instructor presented with sudden onset unilateral facial paresthesia, hand weakness, and blurred vision, accompanied by gradual onset bilateral headache. While the cranial symptoms resolved, left hand weakness persisted for 3 d. MRI revealed two punctate ischemic foci in the right precentral gyrus and superior parietal lobe. A transesophageal echocardiogram revealed a PFO with a small bidirectional shunt. His cardiologist and neurologist advised the PFO was unlikely to have caused his stroke and estimated an annual recurrence rate of &lt; 1.8%. He was treated medically and declined PFO closure. He was able to return to flying light-sport aircraft. However, an enduring copilot restriction for general aviation activities was placed on his Class 1 and 2 medical certificates. DISCUSSION: This case highlights the difficulty in determining individualized recurrence risks for pilots recovering from a stroke associated with a PFO. While medical treatment does reduce the risk of recurrence, PFO closure provides marginal additional benefit in certain patients with a risk of side effects. Contemporary evidence-based risk scoring systems combined with echocardiography findings may be used together to better risk stratify patients and suitability for medical aviation recertification. Rengel AC, Gericke C. Embolic ischemic cortical stroke in a young flight instructor with a small patent foramen ovale. Aerosp Med Hum Perform. 2024; 95(10):784–787.

High hospitalization rates and risk factors among frail patients with cirrhosis: A 10-year population-based cohort study

Cirrhosis-related inpatient hospitalizations have increased dramatically over the past decade. We used a longitudinal dataset capturing a large metropolitan area in the US from 2011-2021 to evaluate contemporary hospitalization rates and risk factors among frail patients with cirrhosis. We conducted a retrospective, longitudinal cohort study using the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN) database, an electronic health record (EHR) repository that aggregates de-duplicated data across seven healthcare systems in the Chicago metropolitan area, from 2011-2021. The primary outcome of our study was the rate of hospitalization encounters. Frailty was defined by the Hospital Frailty Risk Score. Hospitalization rates were reported per 100 patients per year and a multivariable logistic regression analysis identified predictors of annual hospitalization probability. During the study period, of 36,971 patients, 16,265 patients (44%) were hospitalized (compensated: 18.4%, decompensated: 81.6%). Hospitalization rates were highest in patients with decompensated cirrhosis, reaching nearly 77.3 hospitalizations/100 patients per year. Hospitalization rates among patients with compensated cirrhosis were also high (14.2 vs. 77.3 hospitalization/100 patients per year), with odds of annual hospitalization three times (OR 3.1; 95%CI 2.9-3.4) as high among compensated patients with intermediate frailty and five times (OR 5.2; 95%CI 4.5-6.0) as high among those with severe frailty (compared to compensated patients with low frailty). Compensated and decompensated cirrhosis patients with intermediate to severe frailty face a substantially increased odds of annual hospitalizations compared to those with low frailty. Future work should focus on targeted interventions to incorporate routine frailty screenings into cirrhosis care and to ultimately minimize high hospitalization rates.

Surgical closure of ventricular septal defect: Contemporary results and risk factors for electrophysiological changes.

Surgical closure of ventricular septal defect: Contemporary results and risk factors for electrophysiological changes.

TCT-173 Contemporary Risk Prediction and Stratification of Long-Term Major Adverse Cardiac and Cerebrovascular Events After Percutaneous Coronary Intervention: The REMEDY Score

TCT-173 Contemporary Risk Prediction and Stratification of Long-Term Major Adverse Cardiac and Cerebrovascular Events After Percutaneous Coronary Intervention: The REMEDY Score

Body Mass Index Improvement Reduces Total Knee Arthroplasty Complications Among Patients Who Have Extreme, but Not Severe, Obesity

BackgroundWhile morbid obesity has been associated with increased complication risk in primary total knee arthroplasty (TKA), limited evidence is available to attribute decreased surgical complication rates with body mass index (BMI) reduction. MethodsWe retrospectively assessed 464 unilateral TKAs performed in morbidly obese patients, including 158 extremely obese (BMI ≥ 45) and 306 severely obese patients (BMI 40 to 44.9). A detailed medical record review identified concurrent modifiable risk factors and successful preoperative BMI reduction, reaching either a contemporary risk target (BMI < 40) or an institutionally accepted threshold (BMI < 45). Postoperative blood glucose levels and 1-year adverse outcomes (periprosthetic joint infection, wound dehiscence, knee manipulation, periprosthetic fracture) were compared to 557 contemporary control subjects with expected slightly lower (moderate obesity, BMI 35 to 39.9) or sufficiently lower complication risk (overweight, BMI 25 to 29.9). ResultsPeriprosthetic joint infection and postoperative hyperglycemia were identified more frequently among morbidly obese patients in comparison with a moderately obese control group. Extremely obese patients (BMI ≥ 45) whose BMI improved below 45 had no measurable difference in infection risk from the control group (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.04 to 16.88), while those with a nonimproved BMI had a significantly higher risk (OR 7.70, 95% CI 1.89 to 31.41). No significant differences in the risk for infection were observed between severely obese patients (BMI 40 to 44.9) with preoperative BMI improvement (1.5% rate, OR 1.70, 95% CI 0.17 to 16.57) or nonimprovement (1.7% rate, OR 1.87, 95% CI 0.41 to 8.43). ConclusionsPreoperative medical optimization may decrease postoperative TKA complications. The findings of this study support BMI improvement for extremely obese patients (BMI ≥ 45). The assignment of 40 BMI as a threshold for otherwise healthy patients may exclude patients from potential surgical benefits without realizing risk reduction.

Gender and contemporary risk of adverse events in atrial fibrillation.

The role of gender in decision-making for oral anticoagulation in patients with atrial fibrillation (AF) remains controversial. The population cohort study used electronic healthcare records of 16 587 749 patients from UK primary care (2005-2020). Primary (composite of all-cause mortality, ischaemic stroke, or arterial thromboembolism) and secondary outcomes were analysed using Cox hazard ratios (HR), adjusted for age, socioeconomic status, and comorbidities. 78 852 patients were included with AF, aged 40-75 years, no prior stroke, and no prescription of oral anticoagulants. 28 590 (36.3%) were women, and 50 262 (63.7%) men. Median age was 65.7 years (interquartile range 58.5-70.9), with women being older and having other differences in comorbidities. During a total follow-up of 431 086 patient-years, women had a lower adjusted primary outcome rate with HR 0.89 vs. men (95% confidence interval [CI] 0.87-0.92; P < .001) and HR 0.87 after censoring for oral anticoagulation (95% CI 0.83-0.91; P < .001). This was driven by lower mortality in women (HR 0.86, 95% CI 0.83-0.89; P < .001). No difference was identified between women and men for the secondary outcomes of ischaemic stroke or arterial thromboembolism (adjusted HR 1.00, 95% CI 0.94-1.07; P = .87), any stroke or any thromboembolism (adjusted HR 1.02, 95% CI 0.96-1.07; P = .58), and incident vascular dementia (adjusted HR 1.13, 95% CI 0.97-1.32; P = .11). Clinical risk scores were only modest predictors of outcomes, with CHA2DS2-VA (ignoring gender) superior to CHA2DS2-VASc for primary outcomes in this population (receiver operating characteristic curve area 0.651 vs. 0.639; P < .001) and no interaction with gender (P = .45). Removal of gender from clinical risk scoring could simplify the approach to which patients with AF should be offered oral anticoagulation.

Multivariate ocean waves dynamics in North Sea and Norwegian Sea by Gaidai reliability method

Current study presents state-of-the-art approach for evaluating spatiotemporal multivariate environmental risks, especially suitable for complex environmental systems that have been either numerically simulated or physically observed. Advocated methodology provides accurate hazard risk forecasts, based on real-time in situ environmental data. Design of offshore structures requires multivariate risk assessment – offshore and naval operations require both short- and long-term risk and reliability analyses. Contemporary risk evaluation techniques often struggle with raw timeseries multivariate data due to intrinsic multidimensionality and nonlinear interconnections among critical system’s dimensions/components. In the current study effectiveness of the Gaidai multivariate risk evaluation method is illustrated by utilizing significant wave heights dataset, measured within two offshore zones: Heidrun and Troll Norwegian oil fields. Analyzing offshore waves being particularly challenging due to their complexity, high nonlinearity, multidimensionality, yet dynamic inter-correlations. Global warming being among several significant factors, affecting ocean and sea wave heights. For naval, offshore and marine structures operating in harsh weather conditions, robust multivariate environmental risk evaluation methods being crucial for both design and safe operations. Current study aims to validate and benchmark state-of-the-art methodology, enabling extraction. Advocated approach allows for efficient yet accurate assessment of global damages, failures or hazard risks for a wide range of complex nonlinear multivariate environmental and energy systems. Primary advantage of presented multivariate reliability methodology lies within its ability to treat complex systems with practically unlimited number of dimensions, while existing reliability methods being mostly limited to univariate and bivariate analyses.

Modern predictors and management of incidental prostate cancer at holmium enucleation of prostate.

To evaluate contemporary preoperative risk factors and subsequent postoperative management of incidental prostate cancer (iPCa) and incidental clinically significant prostate cancer (icsPCa, Grade Group [GG] ≥ 2 PCa). A retrospective cohort of 811 men undergoing Holmium enucleation of the prostate (HoLEP) (January 2021-July 2022) were identified. Advanced preoperative testing was defined as prostate health index (PHI), prostate MRI, and/or negative preoperative biopsy. Descriptive statistics (Whitney-Mann U test, Chi-squared test) and multivariable logistic regression were performed. iPCa and icsPCa detection rates were 12.8% (104/811) and 4.4% (36/811), respectively. Advanced preoperative testing (406/811, 50%) was associated with younger age and higher (prostate specific antigen) PSA, prostate volume, and PSA density. On multivariable analysis, PHI ≥ 55 was associated with iPCa (OR 6.91, 95% CI 1.85-26.3, p = 0.004), and % free PSA (%fPSA) was associated with icsPCa (OR 0.83, 95% CI 0.67, 0.94, p = 0.01). GG1 disease comprised the majority of iPCa (65%, 68/104) with median 1% involvement. iPCa patients were followed with active surveillance (median follow up 9.3 months), with higher risk patients receiving prostate MRI and confirmatory biopsy. Three patients proceeded to radical prostatectomy or radiation. In the era of MRI and advanced biomarkers, the majority of iPCa following HoLEP is low volume GG1 suitable for active surveillance. A tentative follow-up strategy is proposed. Patients with PHI ≥ 55 or low %fPSA, even with negative prostate MRI, can consider preoperative prostate biopsy before HoLEP.