Logistic Regression Research Articles

Prediction of family inheritance in non-sarcomeric hypertrophic cardiomyopathy using clinical variables and 12-lead electrocardiogram artificial intelligence models

Abstract Background Hypertrophic cardiomyopathy (HCM) can be familial even in the absence of a causative sarcomeric variant, justifying periodical screening of first-degree relatives. However, indiscriminate screening may burden low-risk individuals unnecessarily. The prevalence and predictors of familial disease in non-sarcomeric HCM remain inadequately characterized. Purpose Our study aims to develop a tailored approach to family screening based on index cases’ clinical profiles. By leveraging artificial intelligence (AI) models, we aim to predict the likelihood of family disease using pertinent clinical variables and electrocardiograms (ECGs) from the proband. Methods From January 2008 to June 2022, all probands diagnosed with HCM at our Heart Institute genetics clinic were included if they had i) negative genetic testing for a (likely) pathogenic variant in a sarcomeric gene and ii) ≥1 first- or second-degree relative screened for HCM. The outcome was the presence of family disease defined as left ventricular wall thickness ≥13mm or verified autopsy report confirming HCM. Predictors of family disease were assessed at the first genetic clinic visit and considered age, sex, hypertension, and echocardiography metrics (maximal wall thickness, septal morphology, outflow tract obstruction at rest or Valsava). Using 12-lead ECGs and clinical variables, we used machine learning to train two distinct AI models. Model A utilized ECG signals only to train a ResNet model, while Model B used both ECGs and selected clinical variables (below 0.2 alpha level in logistic regressions) to train a random forest model to predict family disease. We performed evaluations at both ECG-level (one ECG used per patient) and patient-level (all available ECGs used in a patient) and we present individual and ensemble model performance. Results Among 356 families with sarcomere-negative HCM, 106 (30%) were familial. Probands were aged 53 ± 16 years, 30% female, 36% with a diagnosis of hypertension and 43% with peak outflow tract obstruction ≥30mmHg. In univariable logistic regressions, family disease was associated with age at diagnosis (OR 0.89 per 5-year, P=0.003), hypertension (OR 0.60, P=0.046) and obstruction (OR 0.52, P=0.013). The ensemble AI model, which integrated clinical and ECG data, achieved an AUC of 0.82 (95% CI: [0.795, 0.848]). It demonstrated a specificity of 0.891 (95% CI: [0.867, 0.913]) and a negative predictive value of 0.798 (95% CI: [0.772, 0.823]). When comparing ECG-level and patient-level data (1 to 10 ECGs per patient), the models consistently achieved AUC values between 0.78 and 0.81, indicating stable performance across various data subsets. Conclusion The prevalence of family inheritance in sarcomere-negative HCM can be accurately predicted using AI models that integrate clinical variables and 12-lead ECG data. This approach could enable tailored screening strategies based on the likelihood of family disease.

Predictive value of Type D personality combined with unhealthy cardiovascular behaviors for the long-term adverse cardiovascular events in ACS patients

Abstract Background Acute coronary syndrome (ACS) has become a major public health problem worldwide due to its high morbidity and mortality. In addition to traditional risk factors, psychosocial factors play an important role in the development of ACS.Type D personality, as a combination of social inhibition and negative affect, has been defined as a psychological risk factor for coronary heart disease by the European Society of Cardiology.Meanwhile, ACS patients with Type D personality may have behaviors such as unhealthy dietary behaviors, less regular physical activity, and poorer self-management behaviors. Then, whether the combination of Type D personality and poor cardiovascular health behaviors can increase the risk of poor prognosis in patients with ACS requires further research. Purpose The aim of this study was to investigate the effect of Type D personality combined with poor cardiovascular health behaviors on long-term major adverse cardiovascular events(MACE) in patients with ACS. Methods A total of 18631 patients diagnosed with ACS between January 2017 and July 2023 were included in this study. Type D personality, cardiovascular health behaviors (smoking cessation, physical activity, average sleep duration at night, dietary assessment index, BMI, lipids, blood glucose, blood pressure) were assessed during the admission period, and were divided into poor, general, and ideal cardiovascular health with a cut-off score of 50 and 80.The binary logistic regression analysis was used to assese the effect of Type D personality combined with cardiovascular health score on the occurrence of MACE (stroke, reinfarction, revascularization, all-cause death). Results The median follow-up in this study was 37 months, and we found that a total of 3750 people had MACE during the follow-up period. The logistic regression result showed that compared with Type D personality (-) and cardiovascular health behaviors (poor) group, Type D personality (+) and cardiovascular health behaviors (poor) group (OR=1.451, 95%CI=1.055-1.995,P=0.022), Type D personality (+) and cardiovascular health behaviors (general) group (OR=1.425, 95%CI=1.092-1.858,P=0.009), Type D personality (-) cardiovascular health behavior (poor) group (OR=1.301, 95%CI=1.013-1.670, P=0.039) were independent risk factors for the occurrence of further adverse cardiovascular events. Conclusion Type D personality combined with unhealthy cardiovascular behavior individuals may be at high risk for MACE. Therefore, early assessment of Type D personality and cardiovascular health behaviors are needed, thereby reducing the incidence of MACE in ACS patients.

Novel risk scoring model to assess the need for venoarterial-extracorporeal membrane oxygenation in patients with acute myocarditis

Abstract Background Some patients with acute myocarditis unpredictably deteriorate into a fulminant form and their prognosis is poor. However, it is uncertain which acute myocarditis patients are likely to exacerbate and even require venoarterial-extracorporeal membrane oxygenation (VA-ECMO). Objectives This study aimed to identify the risk factors associated with the need for VA-ECMO in patients with acute myocarditis and to develop a predictive model. Methods This retrospective study included 841 patients from seven hospitals in Korea with biopsy-proven or clinically suspected acute myocarditis. Logistic regression was performed to identify clinical characteristics of patients who required VA-ECMO and to construct a scoring system that can predict the need for VA-ECMO. Results Among the study population, 217 (25.8%) patients underwent VA-ECMO. The study population was divided into training (N=621) and testing (N=220) cohorts according to participating center. The final predictive model of VA-ECMO insertion derived from the training cohort included the following: initial mean blood pressure <65mmHg, cardiac arrest, Glasgow Coma Scale ≤12, platelet <100×103/mL, pulmonary congestion on chest X-ray, QRS interval ≥120ms, left or right bundle branch block, and left ventricular ejection fraction <40%. Using this predictive model, a β-coefficient-weighted Korean Acute Myocarditis (KAM) score was developed. The VA-ECMO insertion rate increased with increasing KAM score (odds ratio 1.683, 95% confidence interval 1.529-1.853, P<0.001). External validation of the predictive model and KAM score using the testing cohort showed excellent discriminant ability (areas under the curve of 0.945 and 0.921, respectively). Furthermore, at a KAM score of 8 or higher, which was the cut-off KAM score to predict the need for VA-ECMO, patients without VA-ECMO tended to have higher in-hospital mortality than patients who needed VA-ECMO. Conclusions A risk scoring system based on simple clinical and laboratory parameters at initial presentation could predict the need for VA-ECMO and clinical course in patients with acute myocarditis.Graphic Abstract

Novel scoring system specific for patients treated with micro-axial percutaneous left ventricular assist device

Abstract Background Cardiogenic shock (CS) is characterized by high mortality. The impact of micro-axial percutaneous left ventricular assist devices (ma-pLVAD) remains unclear. Nevertheless, the utilization of these devices increased lately which binds considerable resources. Accurate prognosis assessment is crucial for physicians to identify patients who may benefit from the device upfront. Purpose We developed a novel scoring system predicting 30-day all-cause mortality specifically for CS patients treated with ma-pLVAD. Methods Data were collected from an ongoing Impella registry including more than 830 patients since 2014. Among them, 460 patients received a ma-pLVAD in CS. Based on 53 clinically relevant parameters univariate logistic regressions on 30-day-mortality were performed. Subsequently, parameters with a p-value < 0.1 were included in a multivariate logistic regression analysis (MLRA) using backwards selection by likelihood ratio. The remaining continuous parameters underwent a correlation and regression tree analysis (CART) to define the optimal thresholds and MLRA was performed on all the selected parameters for calculation of odds ratios. These were used for score building. All-cause mortality was assessed by Kaplan-Meier method. Area under the curve (AUC) based on receiver operating characteristic (ROC) was estimated to determine the predictive value of the novel score for 30-day-mortality. Validation was performed on a timely independent cohort of CS patients treated with ma-pLVAD. Results Patients were 68±1 years old with predominance of male gender (74.4% [n=342]). CS was mainly caused by acute myocardial infarction (AMI) (60% [n=276]). A cardio-pulmonary resuscitation before ma-pLVAD was performed in 49.0% [n=215]. Initial serum lactate was 8.6±0.3 mmol/l. All-cause mortality at 30 days was 65.1±2.2% (Fig. 1A). A model of 6 parameters resulted after first MLRA with following odds ratios provided in Tab. 1A. CART analysis revealed optimal thresholds for age with 68 a [Gini-coefficient (G)=0.1], for initial serum lactate with 6.5 mmol/l [G=0.042], thrombocytes with 210 Gpt/l [G=0.021], and mean arterial pressure (MAP) with 70 and 90 mmHg [G1=0.027; G2=0.008]. Results of MLRA on the 6 parameters including the determined thresholds are given in Tab. 1B. A 0 to 17 point risk score resulted by using the odds ratios (Tab. 1C). ROC analysis indicated strong predictive capability for 30-day mortality (ROC AUC [95% CI] 0.767 [0.722-0.811]; p<0.001, Fig. 1B), with discrimination details provided in Tab. 1D. In the validation cohort, the score demonstrated favorable performance (ROC AUC [95% CI] 0.793 [0.607-0.979]; p=0.016; n=24). Conclusion We developed an internally validated, clinically feasible scoring system to estimate 30-day-mortality of CS patients treated with ma-pLVAD. Further studies are mandatory for external validation.

Short-term mechanical circulatory support in adults with congenital heart disease: indications and outcomes

Abstract Background An increasing number of adults with congenital heart disease (ACHD) present with heart failure (HF), which may require short- or long-term mechanical circulatory support (MCS), often around cardiac surgery or other interventions. Even though MCS has entered ACHD practice over the last few years, little is known on its indications and outcomes in this population. Purpose To assess the use and outcomes of short-term MCS in ACHD patients in a specialist centre, and assess the predictive power of the Survival After Veno-Arterial Extracorporeal Membrane Oxygenation (SAVE) score in this population. Methods Data on all ACHD patients who received MCS since 2008 in a single tertiary centre were collected. Immediate, short and longer-term outcomes were also collected, including death, complications, and weaning success. Logistic regression and ROC analysis were performed to identify predictors of in-hospital mortality. Result There were 65 episodes of MCS in 63 patients during the study period: age 36.9+-13.6 years, 61.5% male. Most patients had CHD of moderate or severe complexity (49.2% moderate and 10.8% severe according to ESC guidelines). The most common anatomical diagnoses were left outflow tract obstruction in 35.4%, Marfan syndrome in 20.0% and tetralogy of Fallot or pulmonary atresia in 10.8%. The most common indications for ECMO were perioperative support (not endocarditis) in 55.6%, HF in 14.3%, pneumonia in 12.7% and endocarditis-related surgery in 7.9%. A critical preoperative status was present in 26.8%; median PEACH score (a validated ACHD peri-operative risk score) was 1.0[1.0-3.0] and ACHS score was 0.6[0.6-1.0]. Median SAVE score was -4.0[-9.0–2.0], with 21(43.8%) in SAVE class 4 or 5. VA-ECMO was used in 69.2%, VV-ECMO in 21.5%, BiVAD-ECMO in 4.6% and RVAD support in 4.6% of patients. The median duration of ECMO support was 198.6[133.0-354.2] hours. Complications included ischemic stroke (15.4%), intracerebral bleeding (9.2%), and other thromboembolism (23.8%). Successful weaning was achieved in 56.2%, whereas 4.6% were switched to more definitive MCS. In-hospital mortality was 47.7%, and this was higher in patients receiving VA support (OR 4.92, 95%CI:1.32-23.93, p=0.03). For patients on VA-ECMO or BiVAD support, the presence of Marfan syndrome (OR 4.92, 95%CI:1.32-23.93, p=0.03) and a lower (worse) SAVE score (OR 1.3 per point reduction, 95%CI:1.11-1.59, p=0.004) were associated with in-hospital mortality. An adjusted SAVE score that accounted for the presence of heritable thoracic aortic diseases (HTAD, -3 points) performed well at predicting in-hospital mortality (AUC increasing from 0.73 to 0.8, Figure). Conclusions Short-term MCS is a useful temporary rescue intervention in patients with ACHD, as a bridge to recovery or durable support, with 1 in 2 patients surviving to hospital discharge. The SAVE score adjusted for HTAD can reliably predict outcomes in patients with VA-ECMO and requires external validation.Figure

Subclinical myocardial fibrosis is almost ubiquitous in the hearts of older British persons: 'MyoFit46' cardiovascular sub-study of the NSHD

Abstract Background Unprecedented numbers are now surviving to older age, but little is known about the burden or pattern of myocardial fibrosis in the asymptomatic elderly population. Previous 1.5 Tesla (T) cardiovascular magnetic resonance (CMR) studies found a prevalence of unexpected infarct-pattern late gadolinium enhancement (LGE) of 17-20% above 75 years but less is known about non-infarct pattern scar in this group. We investigated the prevalence, patterns, and clinical predictors of left ventricular (LV) scar in a large asymptomatic older age cohort. Methods CMR with a single 3T magnet was performed on participants all born in the same week in March 1946, as part of the longest running continued surveillance birth cohort: the National Survey of Health and Development. LV short-axis stack LGE imaging was performed using a free-breathing motion-corrected balanced steady-state free precession sequence with phase-sensitive inversion-recovery. Two blinded observers independently recorded the prevalence, extent, and pattern of LGE per participant. Logistic regression was used to study the association between clinicodemographic parameters and LGE. Results 460 participants were prospectively recruited of which 406 completed CMR with LGE imaging (77.8 ± 0.1 years, 44% male). 341 (84%) demonstrated LGE affecting a mean of 2.1±1.2 myocardial segments per participant (Figure 1). The commonest pattern of LGE was inferior right ventricular insertion point (RVIP), observed in 66.9%. Other patterns included (Figure 2): Linear mid-wall (19.6%) of which 38% were located in the inferior/lateral walls; subepicardial (12.1%); subendocardial infarct-pattern (8.8%); patchy/diffuse (1.6%); embolic LGE (0.6%). Sub-analysis was performed comparing those without significant unexpected fibrosis (LGE–) vs those with focal fibrosis (LGE+, excluding RVIP and those participants with a known history of prior myocardial infarction). LGE+ participants were more likely to be female (71.7% vs 49.1%, p<0.001) or diabetic (11.3% vs 5.1%, p=0.05), had a higher body surface area (BSA, 1.9 vs 1.8 m2, p<0.001), weight (80.1 vs 72.8 kg, p<0.001), LV indexed end systolic volume (24.2 vs 20.4 ml/m2, p=0.001) and LV indexed mass (59.2 vs 55.4 g/m2, p<0.001), and a lower LV ejection fraction (67.9 vs 71.8%, p<0.001) In multivariable logistic regression: BSA, LV indexed mass, LV ejection fraction and diabetic status were independently associated with LGE+ status (odds ratios [95% confidence intervals]: 9.4 [0.7–3.8]; 1.0 [0.01–0.05]; 0.9 [-0.08--0.02]; and 2.5 [0.03–1.7] respectively, p<0.05). Conclusion Advanced PSIR MOCO LGE imaging at 3T reveals that the majority (84%) of asymptomatic British persons above the age of 75 harbour unexpected ‘subclinical’ focal fibrosis, with a substantial proportion of these scars consistent with probable historical myocarditis events. Further work will now explore the life-course determinants of this scar burden in the older age human heart.

Educational achievement and health during adolescence in second generation immigrants in Sweden

Abstract Background Over the last decades, immigration have increased markedly in Sweden. Educational achievement is essential for successful integration; however, second generation immigrants have been shown to lag behind. There is a complex intertwinement between educational attainment and health outcomes. Thus, schooling is crucial in terms of integration but also from a public health perspective. We aim to compare school performance and health in children of immigrant parents and children of parents born in Sweden. Methods In this population-based cohort study, 1723 children were followed from birth to age 20. Of these 246 (14.3%) had at least one parent born abroad. Logistic regression was performed controlling for gender, language spoken at home and sociodemographic data obtained at 3 months, 3-, 12- and 20 years. Outcome measures were school performance at age 12 (n = 984), grades from compulsory and upper secondary school (n = 1668) and register data on psychiatric diagnoses (n = 737). Self-response questionnaires on general health, long term health problems and psychiatric conditions were administered at age 20 (n = 731). Results There were no differences in reading (p = 0.676) or mathematics (p = 0.324) at age 12, eligibility to upper secondary school (p = 0.298) or university (p = 0.232) between second generation immigrants and children of native-born parents. No differences in frequency of psychiatric diagnoses (p = 0.112), presence of long-term health problems (p = 0.267) or self-reported health (p = 0.595) were shown. Conclusions The results indicate that young adults born in Sweden in the middle of the 1990’s with immigrant parents perform similarly in school compared to children of parents born in Sweden. They are not at increased risk for mental illness, long-term health conditions and report their general health equivalently to children of native-born. The comprehensive school system and child health programs used in Sweden are likely important factors to promote education and health. Key messages • In a birth-cohort of children followed into early adulthood, no difference in educational achievement or health was shown between second generation immigrants and children of parents born in Sweden. • International comparative studies are needed to highlight the importance of underlying structural and socio-cultural factors.

The trajectory of self-care over a 12-month period in patients with heart failure, comparing those with consistently good and poor self-care

Abstract Background Self-care behaviour plays a pivotal role in enhancing the quality of life for patients with heart failure (HF) and reducing mortality and morbidity rates, but many patients struggle with suboptimal self-care behaviours. It is crucial to understand the factors influencing long-term self-care management. Purpose To assess the trajectory of self-care over a 12-month period and assess differences between patients who have constantly good self-care over a 12-month period compared to constantly poor self-care. Method This study use data from a randomised controlled intervention study, called the HF-Wii study. We included patients who had complete data on self-care during on baseline, 3, 6 and 12 months. Self-care was measured with the European Heart Failure Self-care Behaviour scale (EHFSBs). A threshold score of equal or higher than 70 was used to define self-care behaviour as good and a score lower than 70 as poor self-care. Based on literature, the following characteristics (collected from questionnaires and medical records at baseline) were considered in the analysis: age, sex, marital status, education, history of myocardial infarction, duration of HF, New York Heart Association (NYHA) functional class, LVEF, comorbidity. Other factors assessed were Health-related Quality of Life (HrQoL, Minnesota living with HF questionnaire), depressive symptoms (Hospital Anxiety and Depression scale), cognition (Montreal Cognitive Assessment), sleep (Minimal Insomnia Symptom Scale) and level of HF knowledge (Dutch HF knowledge scale). Logistic regression was performed with backwards elimination of the factors considered associated with the differences between patients who have constantly good self-care at baseline, 3, 6 and 12 months compared to constantly poor self-care. Results In total, 407 patients were included in this study. At baseline, the mean self-care was 65±21, with 41% of the patients (n=245) performing good self-care. In total, 126 patients had a constantly good self-care over 12 month (31%), 120 patients had a constantly bad self-care over 12 months (30%) and 161 (39%) fluctuated in their self-care (Figure). In the multivariate analysis, patients that had continuously good self-care over 12-months were of older age (68±10 vs. 64±12, odds ratio (OR) 1.061, P-value<0.001), had higher HF knowledge (score 13±2 vs. 12±2, OR 1.439, P-value<0.001) and had higher HrQoL (score 28±20 vs 36±22, OR 0.984, P-value=0.022). compared to patients with consistently poor self-care. The variance was explained by 20%. Conclusion Younger patients with HF tend to struggle with consistent self-care over a year, underscoring the necessity for tailored interventions for this group. Conversely, patients with greater HF knowledge and higher HrQoL maintained good self-care habits.

Discordance between symptomatic response and changes in cardiac structure and function one year after transcatheter aortic valve implantation

Abstract Background Symptomatic improvement is one of the main goals of transcatheter aortic valve implantation (TAVI) in patients with severe symptomatic aortic stenosis. We hypothesized that the degree of symptomatic response after TAVI is associated with improvement in cardiac structure and function after TAVI. Purpose We aimed to evaluate 1) the change in symptomatic burden measured by New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) functional class after TAVI, 2) the change in echocardiographic structural and functional parameters after TAVI, and 3) the association of symptomatic response with echocardiographic response as well as long-term survival. Methods In patients undergoing TAVI, we assessed New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) functional class at 12 months. Symptomatic response was defined as NYHA/CCS class I or ≥ 1 improvement in NYHA/CCS class compared to baseline at 12 months. Echocardiographic images at baseline and 6-18 months post-TAVI were analysed using an automated, validated, deep-learning workflow. Logistic regression was used to assess association between change in echocardiographic parameters and symptomatic change at 12 months. The association of symptomatic response and echocardiographic changes in the first 12 months after TAVI with survival beyond 12 months, was evaluated by landmark analysis using Kaplan-Meier analysis. Results Among 868 TAVI patients (median age 80 years, 53% female), the majority (74%) had NYHA/CCS class III at baseline and 77% of patients experienced improvement in symptoms at 12 months post-TAVI (Figure 1). Patients without an improvement in symptoms more often had COPD, atrial fibrillation and more heart failure medications compared to responders. Left ventricular systolic function did not show improvement compared to baseline, whereas a modest improvement in left atrial volume index, left ventricular mass index, E/A ratio, E/e’ ratio, mean e’ and tricuspid regurgitation peak jet velocity was observed. Symptomatic response was not associated with echocardiographic response. Beyond 12 months, patients with symptomatic improvement had lower mortality than those without symptomatic improvement (1.5 vs. 2.4 per 10 patient years; p = .001), whereas changes in echocardiographic parameters were not associated with subsequent mortality (Figure 2). Conclusion Patients undergoing TAVI for symptomatic severe aortic stenosis, showed substantial symptomatic improvement at one year after the procedure, whereas only a modest improvement in echocardiographic parameters was observed. Improvement in symptoms was not associated with improvement in echocardiographic measures of cardiac structure and function. Symptomatic improvement, but not improvement in cardiac structure and function at 12 months, was a strong predictor of subsequent survival.Change in NYHA/CCS class after TAVISymptoms and echo versus mortality

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

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

Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) measurement in the detection of significant CAD in acute chest pain patients triaged using the No Objective Testing (NOT) rule

Abstract Background After rule-out of MI in ED chest pain patients, uncertainty exists with respect to which remaining patients would benefit from objective functional/anatomical testing to detect potential underlying CAD. Using proteomics, we experimentally identified IGFBP-3 as a biomarker to assist this risk stratification and applied its measurement to >3,000 ED patients from 3 separate studies. Methods An isolated rat heart perfusate model coupled to mass spectrometry identified markers of cardiac ischemia. Human cardiac ischemia was carried out using cardiac exercise stress testing (EST, n=12). Temporal changes in IGFBP-3 during experimental MI were determined in patients undergoing septal alcohol ablation (SAA, n=12) and arterio-venous gradients of IGFBP-3 were determined from cases of proscribed cardiac catheterisation (CC, n=14). The ability of IGFBP-3 to assist clinical assessment (ROC analyses, logistic regression, C-statistic, pathways analyses) and ED risk assessment by the No Objective Testing (NOT) rule was carried out on samples from 3 prospectively recruited studies (SPACE, NZ, n=766; APACE, CH, n=1,056; FAST-TRAC, USA, n=1,230). Results IGFBP-3 identified by MS was present in perfusates of ischemic hearts only (n=3). In human cardiac EST, a delta of IGFBP-3 (∆IGFBP-3) between 0-150minutes was seen in positive ischemic tests, but not in controls (n=6 per group, p=0.026). In SAA patients, peripheral IGFBP-3 levels did not change over 24 hours (n=12, p=0.573) whereas in CC patients, significant extraction gradients of IGFBP-3 were seen across the heart and liver (p=0.013, n=14). In ED chest pain patients identified by the NOT rule (n=1,708), ΔIGFBP-3 between presentation and +2 hours (∆ IGFBP-3) was an independent logistic model predictor of unstable angina (n=123) alongside age, sex, cholesterol and Hx of CAD/MI. At 90% specificity, ∆IGFBP-3 improved the sensitivity of the model from 31% to 43%, the PPV 20% to 25% and the NPV from 94% to 95% (p=0.020). IGFBP-3 made a small improvement in "low risk" NOT rule patient identification (29% to 30%), but made a larger improvement to the ROC curve based identification in NOT rule patients for the finding of stenosis >70% on angiography (n=101, AUC clinical model = 0.682; model plus ∆ IGFBP-3 = 0.725, p=0.044). Pathways analyses (that included hs-TnT) in angiography patients (n=224) revealed ∆IGFBP-3 generated a 28% relative increase in low risk case identification (n=46 to 59). Conclusions IGFBP-3 is identified as a novel potential biomarker of cardiac ischemia, that is taken up/degraded across the heart and appears less responsive to complete infarction (MI). 0-2 hour changes in IGFBP-3 (∆ IGFBP-3) in patients identified as eligible for ED based NOT rule inclusion show promise as a useful tool to identify those with significant CAD, evidenced by the diagnosis of unstable angina, positive EST results or findings of 70% occlusion on angiography.

Working in emergency services in Germany: cross-sectional data on violence experience and perception

Abstract Background Violence in emergency medical services (EMS) continues to be a topic of concern. Experiencing violence impedes the workers’ wellbeing, thus impairing the coverage and quality of EMS. We explored employment-related factors associated with violence experience and perception. Methods We conducted an anonymous online-based survey among EMS staff in Germany (09.2023-01.2024). Participants reported on their work setting, frequency of violent experiences and perception of violence. Descriptive statistics and logistic regression were calculated. Results Of 224 participants with completed questionnaires, 86 reported to have been exposed to physical violence (PV) in the past 12 months (Median number of events=2.00) and 129 reported to have experienced non-physical violence (NPV; Median number of events=5.00) with the majority of participants reporting that all cases occurred during assignment (n(PV)=79; n(NPV)=86). Of those, 78 reported PV by patients and 5 by colleagues, while in NPV cases 113 participants experienced violence by patients and 40 by colleagues. Women had a higher probability of reporting PV experiences compared to men (OR = 2.214, p=.010). Reporting NPV experiences was negatively associated with age between 45 and 49 (compared to ≤ 24 years, OR=.291, p=.019) and having worked for the current employer for ≥16 years (OR=.339, p=.035). Participants who have experienced violence in the past year had a higher likelihood of perceiving a general increase in the prevalence of violence in EMS (PV: OR = 6.766, p<.001; NPV: OR = 1.688, p=.047). Conclusions Younger EMS workers with juniority have a higher probability of reporting experiencing NPV. Women are more likely to report experiencing PV. It remains to be explored, if these associations refer to the experiences of violence, to reporting frequency or both. Regardless, the majority of respondents perceive an increase in violence within the work setting of EMS, especially if they have been subjected to it themselves. Key messages • EMS professionals experience significant levels of physical and non-physical violence originating from patients and colleagues. • Sex, age and seniority may affect the likelihood of EMS professionals of experiencing physical or non-physical violence.

Clinical significance of MRI-measured olfactory bulb height as an imaging biomarker of idiopathic Parkinson's disease.

This study aimed to determine whether the olfactory bulb height (OBH) measured using magnetic resonance imaging (MRI) has clinical utility as an imaging biomarker in the evaluation of patients with idiopathic Parkinson's disease (iPD) through its correlation with movement impairment. This retrospective study included cognitively intact patients with suspected parkinsonism. All participants underwent T2-weighted imaging to measure OBH. Logistic regression was used to determine whether OBH was an independent risk factor for distinguishing iPD patients from disease controls, and its relation with clinical parameters related to motor impairment, including clinical laterality, modified Hoehn and Yahr (HY) stage, and Unified Parkinson's Disease Rating Scale (UPDRS) III score, was investigated. Based on the final clinical diagnosis, 79 patients with iPD and 16 disease controls were included. The mean OBH was significantly smaller in iPD than in disease controls (p < 0.0001). OBH was a significant independent predictor of iPD, with a cutoff of 1.52 mm. In the comparison among the ipsilateral, contralateral side of iPD with clinical laterality, and disease control group, the OBH of the disease control group was significantly larger than both the ipsilateral and contralateral sides (P < 0.05). However, there was no significant difference in OBH between the ipsilateral and contralateral sides (p > 0.05). OBH according to HY stage was significantly smaller in HY stage 2-3 groups than in the disease control group (p < 0.001). The correlation analysis between UPDRS III and OBH showed a mild negative correlation (r = -0.32, p = 0.013). MRI-measured OBH is decreased in iPD regardless of age and sex and may be correlated with the progression of motor symptoms in the iPD.

An intergenerational study of mental health among parents and adolescents

Abstract Background The aim of this study was to examine the association between parents’ mental disorders and adolescents’ self-rated health, using both subjective and objective assessment of parents’ mental health status. Methods This cohort study was based on the Danish Future Occupation of Children and Adolescents cohort. Study population 25,891parents (biological parents or registered guardians) linked to 13,067 adolescents. Survey data were merged with register data on parent mental health, and logistic regression was used to analyse association between the register- and self-report data on parents mental health, and self-rated global health among their offspring. Results Adolescents’ self-rated health was associated with their parents’ mental disorders, showing an unadjusted OR of 1.5 (95% CI 1.4-1.6) when assessing parental mental disorders using ICD-10 diagnoses and an unadjusted OR of 2.0 (95% CI 1.8-2.2) when using the adolescents’ self-reported measure on the parental mental disorder. Adjustment for adolescents’ sex, adolescents’ mental disorders during childhood, parental education, and parental labour market attachment led to a decreased association between parents’ mental disorders and adolescents’ self-rated health in both analyses with an adjusted OR of 1.2 (95% CI 1.1-1.4) when assessing parents’ mental disorders using ICD-10 diagnoses and an adjusted OR of 1.8 (95% CI 1.6-2.0) when using the adolescents’ self-reported measure on parental mental disorder. Conclusions This study documents a clear pattern in mental disorders across generations and that parental labour market attachment as well as mental disorders in earlier life phases are risk factors for developing mental disorders in adolescence. The results point to the importance of public health interventions aimed at the more vulnerable group of adolescents, where mental health problems are observed over two generations. Key messages • There is a clear pattern in mental disorders across generations. • Parental labour market attachment are risk factors for developing mental disorders among their offspring.

Characterising Long COVID in an Irish cohort: a study of symptom type, severity and determinants

Abstract Long COVID (LC) is a multisystem disorder impacting 65 million people globally. This secondary analysis of data from the Follow-up After Disease Acquisition (FADA) retrospective cohort study of COVID-19 recovery, aimed to characterise the nature and severity of LC in an Irish sample. The Modified COVID-19 Yorkshire Rehabilitation Scale categorised symptoms. Data analysis employed descriptive statistics and logistic regression. Of 4,671 respondents, 2,338 (50.1%) self-reported LC. LC participants were predominantly female (1,543, 66%), White Irish (1,512, 84.9%), and highly-educated (1,174, 65.8%). 907 (51.5%), had ≥one baseline co-morbidity. Most (1,076, 59.1%) had never smoked. Only 6.9% (162) of LC cases were ever hospitalised with acute COVID-19. Recovery was reported by 979 (41.9%). Of those with persistent symptoms 306 (31.6%) were classified as “moderate/severe.” Fatigue was predominant, (1,021, 75.1%) accompanied by cognitive dysfunction (932, 68.5%) and breathlessness (870, 64.0%). Functional impairment, assessed by the EQ-5D-5L score, was evident. Factors associated with LC persistence and severity included baseline co-morbidities (aOR persistent LC 1.44 [95% CI 1.12-1.85], p = 0.005; aOR moderate/severe LC 2.90 [1.92-4.37] p &amp;lt; 0.001)), smoking (aOR persistent LC 1.59 [1.11-2.28] p = 0.01, aOR moderate/severe=1.65 [1.0-2.71] p = 0.05), and meeting/exceeding WHO’s physical activity guidelines (aOR persistent LC 1.49 [1.16-1.92], p = 0.002, aOR moderate/severe=1.69 [1.12-2.54], p = 0.01). LC’s diverse symptomatology and functional impairment serve as a call to action to the health service to equip itself to address this complexity. This study offers insights into LC symptom type, duration, and determinants, emphasising the need for Public Health to traverse domains, to improve all facets of population health. These findings add to the current understanding of LC, providing a foundation for the development of tailored LC services. Key messages • Long COVID causes a constellation of diverse symptoms. • The Irish Health service needs to be equipped to manage the diverse symptomatologu.

Bias analysis on socioeconomic status and lung cancer in a pooled international case-control study

Abstract Background Low socioeconomic status (SES) groups showed increased lung cancer risks even after adjustment for smoking habits and other exposures to lung carcinogens. Although several biases were often indicated and discussed, only few studies quantified the impact of potential biases. Methods We conducted a bias analysis on the association of lung cancer and SES using data from the SYNERGY project, including 12 case-control studies with 18 study centres from Europe and Canada (16,550 cases, 20,147 controls). SES in quartiles was derived from the International Socio-Economic Index of occupational status (ISEI). Odds ratios (OR) with 95% confidence intervals (CI) were estimated by logistic regression adjusting for age, study centre, and smoking. In addition, we estimated natural direct SES effects and natural indirect smoking effects by inverse odds ratio weighting. In a multiple quantitative bias analysis, we considered impacts of misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by a protective genetic factor, and created 95% simulation intervals (SI) by bootstrap. All analyses were stratified by sex. Results Adjustment for smoking as well as natural effects estimation showed that nearly half of lung cancer risks of lower SES groups in men and up to one third in women were attributable to smoking. Consideration of all types of bias reduced lung-cancer risks in the fully adjusted logistic regression models, with the strongest impact by selection bias: For the 4th versus 1st (highest) ISEI quartile OR decreased from 1.83 (1.69-1.98 CI) to 1.50 (1.30-1.73 SI) in men, and OR 1.48 (1.27-1.72 CI) to 1.20 (0.96-1.53 SI) in women. Conclusions Smoking is the main target for prevention of lung cancer, along with occupational and environmental exposures, in particular in lower SES groups. This finding remains, though our analysis revealed reduced lung-cancer risks of lower SES groups after multiple bias adjustment. Key messages • Impact of potential biases was quantified in the association of SES and lung cancer. • Lung cancer risks were partially attributable to smoking and multiple biases.

Biochemical variables as predictors of in-hospital mortality in patients with acute coronary syndrome

Abstract Background There is a constant search of easily obtainable variables that can be put in relation with in-hospital mortality, enabling creation of prediction risk models in patients treated for acute coronary syndrome. Purpose The main goal of this study was to unravel what is the profile of the patients with acute coronary syndrome in risk of in-hospital mortality, based on simple biochemical variables acquired at the time of hospital admission. Methods This was a single-center cross-sectional cohort study on 3007 pts. treated for ACS (STEMI and NSTEMI). Venous blood sample at hospital admission was acquired for every patient. Patients were comparatively analyzed for their biochemical variables derived from venous blood sample, based on occurrence of in-hospital mortality. Results Out of 3007 pts, 988 (28.2%) were females, and 2519 (71.8%) males, at mean age 62.6 +/- 11.2 y. In-hospital mortality rate was 4.8% (145 out of 3007). We subjected to comparative analyzed hemogram, markers of renal function including sodium and potassium, glycemic profile, complete lipid panel (including ApoA1 and ApoB), and highly sensitive troponin. Significant association with in-hospital mortality was found for: hsTn, stress glycemia and glicated hemoglobin, BUN, creatinite, eGFR, sodium, potasium, full lipid panel [except for HDL-C and Lp(a)]. In the second step, markers proven to be significantly different were subjected to multivariate binary logistic regression (backward conditional). We designed two models, one that included ApoA1 and ApoB (including 1816 pts. for whom we had data), and the second without these two parameters (including 3007 pts.). With the first model we identified: Advanced age, stress glycemia, WBC, eGFR, HDL-C and ApoA1 as independent predictors. Surprisingly, HDL-C was found to be strong independent predictor in multivariate analyzis. While with second modeling we identified advanced age, hsTn, stress glycemia, RBC, WBC, BUN and eGFR as independent predictors. Conclusion Advanced age is a strong independent predictor in any modelling. When we have a possibility to obtain a complete lipid panel, beside stress glycemia and WBC as markers of the degree of neuro-hormonal activation and inflammation, and renal function, HDL-C and ApoA1 seems to be strong negative independent predictors. In the absence of this data beside aforementioned markers of neurohormonal activation and inflammation, and renal function, the degree of myocardial injury plays a significant role. According to our data it seems reasonable to obtain complete lipid panel at hospital admission.Multivariate logistic regression modelsAge distribution across genders

Combined activation of complement and coagulation is associated with myocardial injury in ST-elevation myocardial infarction

Abstract Introduction Experimental data indicates that the complement system and the coagulation cascade can activate each other. The magnitude of this interaction in acute myocardial infarction is not known. We aimed to investigate a possible association between complement activation and coagulation activation in patients with acute ST-elevation myocardial infarction (STEMI), as well as how they relate to myocardial injury estimated by troponin T (TnT) and myocardial function assessed by echocardiography. Purpose To increase the understanding of the interaction between complement activation and coagulation activation in STEMI, and the clinical relevance to myocardial injury. Methods Blood samples were drawn after percutaneous coronary intervention (PCI) in 864 patients with STEMI. Myocardial function was measured as left ventricular ejection fraction (LVEF), estimated by visual approximation or Simpson biplane method within 3 months. Complement activation was assessed by ELISA of circulating levels of the terminal complement complex (TCC). Activation of coagulation was assessed by ELISA of prothrombin fragment 1+2 (F1+2) and D-dimer, and endogenous thrombin potential (ETP), analyzed by calibrated automated thrombogram assay. Results TCC was weakly correlated to F1+2 (r=0.086, p=0.012), D-dimer (r=0.176, p&amp;lt;0.001) and ETP (r=0.144, p&amp;lt;0.001). In univariate linear regression analysis, this association persisted for D-dimer and ETP. When adjusting for associated covariables, the association only persisted for ETP (Table 1). Patients with above-median TCC and D-dimer had significantly higher peak TnT (Figure 1). In logistic regression, having combined above-median TCC and D-dimer was predictive of an LVEF ≤40% (Table 2). Conclusion In this large STEMI cohort, complement activation by TCC was weakly associated with coagulation activation. Combined high levels of TCC and D-dimer were linked to higher peak TnT and lower LVEF, possibly reflecting greater myocardial injury. The interaction between complement and coagulation activation might be relevant for clinical outcomes in STEMI patients and warrants further investigation.

Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?

Abstract Background Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort. Methods Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis. Results 65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p&amp;gt;0.05; Table 1). Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p&amp;gt;0.05). There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p&amp;gt;0.05). At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p&amp;lt;0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p&amp;lt;0.0001). Conclusion ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics

The intra-tumoral microbiome as a potential biomarker of response to external beam radiation therapy in cervical cancer

BackgroundWe aimed to determine the potential predictive value of the intra-tumoral microbiome as a marker of the response to external beam radiation therapy (EBRT) in cervical cancer (CC).MethodsA prospective longitudinal trial of 36 CC patients receiving pelvic radiotherapy was designed to investigate microbial characteristic signatures and diversity (alpha and beta) of multiple sites (tumor, vaginal, gut, urethral, and oral) in the superior response (SR) and inferior response (IR) groups of CC patients by 16S rRNA sequencing. Utilized the least absolute shrinkage and selection operator (LASSO) logistic regression method to analyze clinicopathological factors that potentially influenced the efficacy of EBRT. LEfSe analysis highlighted the microbiome features that best distinguished the categorized patient samples. Selected parameters were validated with Spearman correlation analysis, receiver operating characteristic (ROC) area under the curve (AUC) analysis and Kaplan-Meier survival analysis.ResultsFirstly, in our cohort, LASSO logistic regression analysis revealed no association between clinicopathological factors and EBRT efficacy. Subsequently, we employed 16S rRNA sequencing to compare microbiome differences across multiple sites and their correlations with major clinicopathological factors. We discovered that the intra-tumoral microbiome was independent of clinicopathologic features and represented the most direct and reliable reflection of the microbial differences between the SR and IR groups. We found lower alpha diversity in the tumor microbiome of SR group and identified the most relevant microbiome taxa (Bifidobacteriaceae, Beijerinckiaceae, and Orbaceae) associated with the efficacy of the response to EBRT in CC patients. We then conducted ROC analysis, finding that specific microbial taxa had an AUC of 0.831 (95% CI, 0.667–0.995), indicating the potential of these taxa as biomarkers for predicting EBRT efficacy. Kaplan-Meier survival analysis showed a better prognosis for patients with lower alpha diversity and higher relative abundance of Bifidobacteriaceae.ConclusionsOur data suggested that intra-tumoral specific microbiome taxa and lower alpha diversity may play an important role in the CC patient sensitivity to EBRT and offer novel potential biomarkers for predicting the response to EBRT efficacy.