Risk Categories Research Articles

Pregnancy in women with congenital heart disease : new insights into neonatal risk predictioc

Abstract Background Advances in managing adult congenital heart disease (ACHD) have led to an increased number of women with CHD reaching childbearing age. This demographic shift underscores the need for improved understanding and prediction of complications during pregnancy in this specific ACHD population. Despite progress in maternal cardiac risk assessment, the prediction of neonatal outcomes for ACHD pregnancies remains underdeveloped. Therefore, the aims of this study are (1) to assess neonatal outcomes in a CHD women population, (2) to identify their predictive factors and (3) to propose a new risk score for predicting neonatal complications. Methods This registry study included all women born between 1975 and 1996 diagnosed with ACHD who underwent at least one cardiology consultation for ACHD in Cliniques Universitaires Saint-Luc. A multivariate analysis was performed to identify predictors of neonatal complications and these were incorporated into a new risk index. Its validity was assessed using bootstrap method. This score was then compared with scores adapted from the ZAHARA and CARPREG studies for offspring events prediction. Results Analysis of 491 pregnancies revealed 31.4% of neonatal complications. Four significant predictors of adverse neonatal outcomes were identified: cardiac treatment during pregnancy (OR 14.9, 95%CI [4.6-64.3]), hypertensive disorders of pregnancy (OR 10.4, 95%CI [3.4-39.5]), smoking during pregnancy (OR 10.3, 95% CI [3.0-44.9]), and pre-pregnancy BMI < 18.5 kg/m² (OR 6.2, 95% CI [2.6-16.5]). The risk model demonstrated an AUC of 0.70 (95% CI [0.65-0.75), which remained stable after bootstrap validation. This model significantly outperformed the scores adapted from ZAHARA and CARPREG data. Based on the regression coefficients, a risk score was subsequently developed comprising 5 risk categories. Conclusion One third of ACHD pregnancies are complicated by poor neonatal outcome. These complications are determined by 4 independent factors relating to the cardiac and non-cardiac status of the patients, which have been incorporated into a risk score. Our study is one of the first to propose a predictive risk score of neonatal outcomes in ACHD pregancies, and paves the way for other validation and confirmation studies.Offspring scores: performance comparisonNew risk score for neonatal outcome

Cardiological monitoring during BTK inhibitor, ICI, and RAF/MEK inhibitor therapy: the single-center prospective registry for cardiovascular events under new cancer therapies (RECENT)

Abstract Background The advent of novel targeted cancer therapies have revolutionized cancer treatment. However, concerns about their impact on cardiovascular health persist and current guidelines recommend cardiac monitoring. Yet, prospective data on incidence rates of cardiovascular events are lacking. The Registry for Cardiovascular Events under new cancer Therapies (RECENT) aims to systematically assess clinical as well as subclinical cardiovascular incidents in patients undergoing these novel therapies to identify baseline risk factors and derive individualized monitoring strategies. Methods This ongoing single-center prospective registry enrolls cancer patients receiving BTK inhibitors, ICI, or RAF/MEK inhibitors. Baseline cardiovascular assessment, risk stratification according to HFA-ICOS risk score, and follow up visits for 12 months at three-monthly intervals (including ECG, biomarkers and echocardiography) during treatment are conducted. Treatment-related events, in particular hypertension, arrhythmias, cancer therapy-related cardiac dysfunction (CTRCD), and (peri-) myocarditis, as defined according to current guideline recommendations, are recorded. Results We report data of the first 85 patients (60.9 ± 14.7 years, 52.9% male) included in this ongoing registry. Of those, 17/85 patients received treatment with BTK inhibitors (20%), 45/85 with ICI (53%) and 23/85 with RAF/MEK inhibitors (27%). Most common treatment indication were dermatological (39/85, 45.9%), hematologic (17/85, 20%), urological (13/85, 15.3%) and head and neck (11/85, 12.9%) cancers. Before treatment, the majority of patients were stratified as low-risk (31/85) or moderate-risk (32/85), and 22/85 (25.9%) as high-risk. 7/85 (8.2%) patients were newly diagnosed with cardiovascular disease at baseline visit, resulting in a change in risk category and subsequent initiation of cardiovascular treatment. This includes 3 patients who had been initially categorized as low-risk and would not have been referred for further cardiac workup due to current guideline recommendations. The six months follow up visit has been completed in 44/85 patients. Among these, 1/20 patients (5%) with ICI developed a perimyocarditis and 2/11 patients (18.2%) with BTK inhibitors developed atrial fibrillation. 1/13 patients (7.7%) with RAF/MEK inhibitor therapy, classified as low-risk at baseline, developed asymptomatic CTRCD, which resolved after initiation of cardioprotective drug therapy. Conclusion This interim analysis of the RECENT registry indicates benefit of a structured baseline cardiac assessment prior to cancer treatment in all patients, irrespective of the initial risk stratification. Contrary to current guidelines, which recommend routine echocardiographic monitoring in patients receiving RAF/MEK inhibitors only in high-risk patients, the current data advocate for extending this also to low-risk patients to detect subclinical deterioration of the cardiovascular status.

Enhancing primary prevention: the incremental predictive value of NTproBNP beyond ASCVD risk assessment

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is a global health challenge, prompting widespread use of conventional risk assessment tools (SCORE2 in Europe and the ASCVD Risk calculator in the United States) to guide preventive strategies. Emerging evidence indicates that NTproBNP may help refine risk stratification. We investigate whether measuring NTproBNP in primary prevention correlates with mortality and enhances prediction compared to conventional risk score stratification. Methods Utilizing National Health and Nutrition Examination Survey (NHANES) data (1999 to 2004) linked to the National Death Index, our cohort included individuals without a history of CVD at baseline and suitable for assessment of the ASCVD ACC/AHA risk score. Individuals were grouped based on computed 10-year risk (low: <5%; borderline: 5-7.5%; intermediate: 7.5-20%; high: ≥ 20%). NTproBNP levels were measured (Roche assay, cut-off > 125pg/mL considered as positive). Cox regression estimated the association between ASCVD risk categories, with or without NTproBNP, and all-cause and cardiovascular mortality. Results Among 5257 adults, 47% male, mean age 54 ± 9.1 years, the mean 10-year ASCVD risk was 8.17 ± 8.2%, grouped as: low: 53.3%; borderline: 11.5%; intermediate: 23.9%; and high: 11.3%. NTproBNP > 125pg/mL was measured in 12.2%, 16%, 23.2% and 48.6% individuals, respectively (p < 0.001). Over 16.2 ± 3.4 years, all-cause and cardiovascular death was 22.3% and 5.6%, respectively. Compared to low-risk, the hazard ratio (HR) for all-cause death increased to 2.85 (2.2-3.7), 5.6 (4.2-7.5), and 15.3 (11.7-19.9) for borderline, intermediate, and high-risk, respectively. A significant interaction with NTproBNP was observed (low: HR 1.96 (1.33-2.9); borderline: HR 2.5 (1.6-3.9); intermediate: HR 2 (1.6-2.6), high: HR 1.7 (1.4-2.2), p<0.01 for all interactions, see Fig. 1). For cardiovascular death, a significant interaction also occurred across the groups, but of higher magnitude in low and borderline groups (low: HR 3.2 (1.4-7.3); borderline: HR 5.5 (2.5-12.4), p < 0.001 for both). Conclusion Our findings suggest that NTproBNP provides incremental predictive value, approximately doubling the hazard of all-cause death across all risk categories, and more than tripling the hazard of CV death in low/borderline risk groups, compared to ASCVD risk alone. The integration of NTproBNP measurements into risk assessment strategies could refine primary prevention approaches.

Early risk stratification of patients after successfully resuscitated out-of-hospital cardiac arrest without ST-segment elevation - the TOMAHAWK risk score

Abstract Background Mortality after out-of-hospital cardiac arrest (OHCA) remains high. Early risk stratification is crucial to make adequate treatment decisions. Existing OHCA risk scores are either medically outdated, limited to registry data, small cohorts, certain healthcare systems only or include complex calculations. Purpose The aim of this study was to develop an easy-to-use, readily available risk prediction score for short-term mortality in patients with successfully resuscitated OHCA without ST-segment elevation, derived from the TOMAHAWK (Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation) trial. Methods The risk score was developed using a backward stepwise regression analysis. The risk score was externally validated in the COACT (Coronary Angiography after Cardiac Arrest Trial) cohort, which included patients with shockable rhythms only. Results Development and validation of the risk score was performed across 50 centres in three countries. Five variables emerged as independent predictors for 30-day mortality and were used as risk score parameters: age ≥72 years, known diabetes, unshockable initial electrocardiogram rhythm, time until return of spontaneous circulation ≥23 minutes and admission serum lactate level above 7.9 mmol/L. Between 1 and 4 points were attributed to each variable, leading to a score with three risk categories: low (0 to 2), intermediate (3 to 6) and high (7 to 10). The observed 30-day mortality rates were 23.6%, 68.8% and 86.2%, respectively (p<0.001) with a very good discrimination at an area under the curve of 0.82. Kaplan-Meier analysis revealed a stepwise increase in mortality between the different risk score categories (p<0.001 for low vs. intermediate, intermediate vs. high and low vs. high; see Figure). External validation in the COACT cohort showed short-term mortality rates of 23.1% (score 0 to 2), 44.8% (score 3 to 6) and 78.9% (score 7 to 10), respectively (each p<0.001). Conclusion The TOMAHAWK risk score can be easily calculated in daily clinical practice and is strongly correlated with mortality in patients with successfully resuscitated OHCA without ST-segment elevation. It may help stratify patient risk for short-term mortality and facilitate clinical decision making.

Validation of the HFA-ICOS risk assessment tool with real-world data from a prospective cohort of breast cancer patients in treatment with anthracyclines and trastuzumab

Abstract Background The increasing prevalence of cancer therapy-related cardiovascular toxicity (CTRCD) poses a significant challenge to patient management, necessitating accurate risk assessments. Previous methodologies have struggled with precise risk stratification, partly due to varying definitions of CTRCD and the specificity of cancer treatments. Purpose This study aimed to evaluate the assessment tool proposed by the Heart Failure Association and the International Cardio-Oncology Society (HFA-ICOS) in predicting the risk of CTRCD in patients undergoing anthracycline and trastuzumab treatment for breast cancer at a national reference center. Methods A prospective cohort study was conducted, encompassing 172 patients treated from January 2022 to July 2023. Patients were assessed at baseline, three months, and six months post-treatment initiation, with exclusion criteria including baseline left ventricular ejection fraction (LVEF) <50%, history of heart failure, and stage IV breast cancer. The study utilized the HFA-ICOS tool for risk stratification and CTRCD was defined with the current criteria of the European Society of Cardiology guideline. Descriptive statistics were calculated, and incidence rates and Cox proportional-hazards models were developed according to the risk category. Results In our study, 138 (80.2%) patients were classified as low risk, 23 (13.4%) as moderate risk and 11 (6.4%) as high risk. We identified 81 (47.1%) patients that developed CTRCD in follow-up. Descriptive characteristics can be found in Table 1. The global incidence rate for CTRCD in our cohort was of 2.4 new cases per 1000 person-days, however no differences in incidence rates were found when stratifying by risk category (Figure 1A). Moreover, patients with moderate to high risk according to the HFA-ICOS tool did not show a significantly increased hazard ratio for cardiotoxicity (HR 0.41, 95%CI 0.15-1.12, p=0.082 and HR 1.39, 95%CI 0.50-3.86, p=0.5, respectively) as shown in Figure 1B. Conclusion While the HFA-ICOS tool provides a structured framework for assessing cardiotoxicity risk, its predictive value in this cohort was limited. The findings underscore the complexity of cancer therapy-related cardiotoxicity and the need for enhanced, individualized risk assessment tools. Future research should focus on refining risk prediction models, incorporating broader clinical and genetic factors to improve patient outcomes in cardio-oncology.Table 1.Clinical CharacteristicsFigure 1.Incidence rates and Cox models

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Echocardiographic variables may improve baseline risk prediction of cancer therapy related cardiac dysfunction

Abstract Background Baseline prediction of cancer therapy related cardiac dysfunction (CTRCD) in clinical practice is difficult, despite many known cancer and cardiovascular risk factors. Risk scores exist, including the HFA-ICOS score which is recommended by the 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines. Validation of such risk scores is required though, and identification of alternative risk factors that may improve risk prediction is needed. Purpose To assess the accuracy of the HFA-ICOS score for predicting CTRCD, and identify new risk factors with a focus on baseline echocardiography. Methods Echocardiograms and medical records were assessed for a cohort of breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring. CTRCD was defined according to the 2022 ESC Cardio-Oncology guidelines. Baseline risk factors and echocardiography were compared between CTRCD and non-CTRCD groups, and the accuracy of the HFA-ICOS score in predicting CTRCD assessed. Results Data from 258 patients were analysed with CTRCD occurring in 23 (9%). 135 were low risk, 85 moderate-risk, 31 high-risk and 8 very high-risk according to the HFA-ICOS score with a trend of increasing rates of CTRCD with each risk category: 5%, 12%, 10%, 25%, respectively. The sensitivity and specificity of a combined moderate/high/very high-risk group was 70% and 54% (AUC 0.618, 95% CI 0.5-0.73). Only three individual baseline variables were associated with CTRCD in this cohort; ejection fraction 50-54%, (18% vs 2%, p=0.0027), borderline/abnormal average global longitudinal strain <-18, (43% vs 19%, p=0.04) and combination anthracycline plus trastuzumab, (45% vs 22%, p=0.0392). Left atrial volume index >34mL/m² was also higher in the CTRCD group (38% vs 23%) although not statistically significant. A simplified risk score using only these variables yielded a sensitivity and specificity of 74% and 53%, respectively (AUC 0.633, 95% CI 0.52-0.75). Conclusion Baseline prediction of CTRCD remains difficult in clinical practice. Although HFA-ICOS risk categories correlate with CTRCD diagnosis, the overall sensitivity is only moderate. Echocardiographic variables may further enhance risk prediction to enable development of targeted monitoring strategies.HFA-ICOS risk score categoriesROC curves

Enhancing primary prevention: the incremental predictive value of high-sensitivity cardiac troponin T beyond ASCVD risk assessment

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) is a global health challenge, prompting widespread use of conventional risk assessment tools (SCORE2 in Europe and the ASCVD Risk calculator in the United States) to guide preventive strategies. Emerging evidence indicates that high-sensitivity cardiac troponin (hsTn) may refine risk stratification. Objective We investigate whether measuring hsTnT in primary prevention correlates with mortality and enhances prediction compared to conventional risk score stratification. Methods Utilizing National Health and Nutrition Examination Survey (NHANES) data (1999 to 2004) linked to the National Death Index, our cohort included individuals without a history of CVD at baseline and suitable for assessment of the ASCVD ACC/AHA risk score. Individuals were grouped based on computed 10-year risk (low: <5%; borderline: 5-7.5%; intermediate: 7.5-20%; high: ≥ 20%). hsTroponin T levels were measured (Roche assay, 99 th percentile 22ng/L for men and 17ng/L for women). Cox regression estimated association between ASCVD risk categories, with or without hsTnT, and all-cause and cardiovascular mortality. Results Among 5257 adults, 47% male, mean age 54 ± 9.1 years, the mean 10-year ASCVD risk was 8.17 ± 8.2%, grouped as: low: 53.3%; borderline: 11.5%; intermediate: 23.9%; and high: 11.3%. hsTnT above the 99 th percentile was measured in 1.1%, 2.7%, 4.9% and 13.4%, respectively (p < 0.001). Over 16.2 ± 3.4 years, all-cause and cardiovascular death was 22.3% and 5.6%, respectively. Compared to low-risk, the hazard ratio (HR) for all-cause death increased to 2.85 (2.2-3.7), 5.6 (4.2-7.5), and 15.3 (11.7-19.9) for borderline, intermediate, and high-risk, respectively. A significant interaction with hsTnT above 99 th percentile was observed (low: HR 3.5 (1.3-9.2); borderline: HR 4.75 (2.1-10.8); intermediate: HR 2.6 (1.8-3.7), high: HR 2.2 (1.7-2.9), p<0.01 for all interactions, see Fig. 1). For cardiovascular death, a significant interaction occurred in intermediate (HR 3.3 (2-5.4), p<0.001) and high-risk (HR 3.6 (2.2-6), p<0.001) groups. Conclusion Our findings suggest that hsTnT provides incremental predictive value, at least doubling the hazard of all-cause death across all risk categories, and tripling the hazard of CV death in intermediate and high-risk groups, compared to ASCVD risk stratification alone. The integration of troponin measurements into risk assessment strategies could refine primary prevention approaches.

The CTOX-Score, a clinical risk prediction tool for cardiovascular toxicity secondary to cancer therapies

Abstract Introduction Cardiovascular toxicity (cardiotoxicity) is recognized as a major side-effect of cancer therapies. As early diagnosis and management is crucial in clinical practice1,2, knowledge about risk factors and risk scores is scarce3,4. Purpose The aim of this study is to develop a clinical prediction score to identify patients at high/very high risk of cardiotoxicity. Methods The CARDIOTOX registry5,6 included patients receiving cancer therapies related to moderate/high risk for cardiotoxicity (2012-2017). Clinical, laboratory and echo parameters were collected at baseline and at 3 weeks, 3 and 6 months, 1, 1.5 and 2 years after initiation of cancer therapy. Patients were classified according to current cardioncology guidelines2 and divided in two groups: no or mild cardiotoxicity vs moderate or high cardiotoxicity. Difference between groups were tested with t-student or U Mann-Withney for continuous variables and Fisher’s exact test for categorical data. Variables with p<0.05 were included in a multivariate binary logistic regression model to find independent predictors of cardiotoxicity and construct a clinical risk score, CTOX-Score. The calibration was evaluated by Hosmer-Lemeshow goodness-of-fit test and discrimination using ROC curves. Results From the 1324 individuals included in the registry we discarded all those with pre-existing symptomatic heart failure or LVEF<40% at baseline and those with incomplete baseline data. We considered 998 patients, aged 54.62±14.15 years, 176 men (17.6%), of which 53 (5.3%) developed moderate or severe cardiotoxicity. These patients had lower baseline LVEF (59.91±7.50% vs 64.20±5.88%), higher creatinine levels (0.90 (0.76, 1.10) mg/dl vs 0.74 (0.62, 0.90) mg/dl) and higher NT-ProBNP (177 (58, 476) pg/ml vs 66 (38, 133) pg/ml) compared with patients with no or mild cardiotoxicity (p<0.001). We found previous radiotherapy (OR=4.66, CI:1.24-17.52), acute myeloid leukemia (OR=6.85; CI:1.16-40.50), monoclonal antibodies (OR=3.27; CI:1.35-7.89), LVEF (OR=0.96; CI:0.84-0.98) and serum creatinine (OR=5.43; CI:1.63-18.14) as independent predictors of cardiotoxicity (p<0.05). A clinical risk score was developed based in beta coefficient of variables (Table 1). The model has good calibration according to Hosmer-Lemeshow goodness-of-fit (χ2=2.800, p=0.424) and good discrimination power (AUC:0.780, CI:0.69-0.87; p<0.001). The best cut-off value of CTOX-Score is ≥3 points (Sensitivity:70.00%, Specificity:72.25%, NPV:98.11%). Patients were classified in four risk categories: low (0-1 points); moderate (2); high (3-4); very high (≥5) (Figure 1). The model has good accuracy to identify very high-risk patients (Specificity 98.80%). Conclusion The CTOX-Score is a clinical risk prediction model to identify patients at high/very high-risk of cardiotoxicity and could allow for more personalized monitoring of patients. Additional studies are needed to externally validate the model prior to implementation in clinical practice.Multivariate binary logistic regressionCTOX-Score values among population

Baseline characteristics, management patterns and outcome in patients with pulmonary embolism and malignancy: Insights from a single-centre study

Abstract Background and aim The presence of malignancy is an important factor that increases the risk of venous thromboembolism. On the other hand, acute pulmonary embolism (PE) is one of the main causes of death in this setting. In this study, we evaluated the impact of active malignancy on the treatment choices, and short and long term clinical outcomes in patients with acute PE. Methods In this study conducted in a tertiary center, 872 acute PE patients (age 61.6±16.8 years, female 57.5 %) from different risk categories were treated with thrombolytic, anticoagulant and catheter-based therapies in accordance with currently available acute PE guidelines. The population was retrospectively analyzed and divided into two groups according to the presence of active malignancy. Results Active malignancy was documented in 129 (14.8 %) patients. In the groups with and without malignancy, the proportions of low-, intermediate-low-, intermediate-high-, and high-risk PE patients were 3.1 % vs. 15.6 %, 17.8 % vs. 16.7 %, 60.5 % vs. 60 %, and 18.6 % vs. 7.7 %, respectively (p<0.001). While the two groups did not differ in terms of echocardiographic and computed tomographic pulmonary angiography (CTPA) characteristics, the presence of contraindications for thrombolytic were more frequent in the malignancy group (22.5% vs. 10.9%, p<0.001). Ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy (RT), systemic thrombolysis (ST) and anticoagulation-alone (AC) therapies were noted in 27.3 %, 6.4 %, 6.4 % and 49.7 % of overall PE patients. The RT and AC therapies were more frequent in PE patients with malignancy whereas ST and USAT were more frequently used in the absence of malignancy. Notably, lytic dosages and treatment durations in USAT and ST protocols were comparable between malignant and non-malignant PE cohorts. Regardless of the presence of malignancy and the treatment modality chosen, significant improvements were achieved in the clinical, echocardiographic and CTPA measures of the PE severity (p<0.001 for all). Major and minor bleeding rates were also similar in both groups, while in-hospital and, as expected, long-term mortality were higher in the malignancy cohort. Active malignancy and PESI score were found to be independent predictors for composite end-point of 60-day mortality and PE-related rehospitalization (adjusted odds ratio (OR): 2.43; 95 % CI: 1.32 - 4.47, p=0.04) and (OR: 1.02; 95 % CI: 1.01-1.01, p<0.001), respectively. Malignancy (OR: 3.5, 95 % CI: 2.15-5.75, p< 0.001) and chronic obstructive pulmonary disease (OR: 2.51, 95 % CI: 1.35-4.68, p< 0.003) were independent predictors of long-term mortality. Conclusion Concomitant malignancy adversely affects both short- and long-term outcomes in patients with acute PE. Although these patients are more vulnerable, it is possible to achieve satisfactory treatment success with acceptable bleeding rates with the inclusion of catheter-based methods as treatment option.Survival plot

A novel 12-lead standard ECG derived scoring system for risk stratification in the emergency department

Abstract Background/Aims The ECG represents a routinely used diagnostic tool in the assessment of patients in the emergency department. Beside specific alterations within the ECG indicative of underlying pathologies, such as ST-elevation in myocardial infarction, several other parameters have been developed over the past decades that proofed themselves as strong and independent predictors of worsened outcome independent of a specific underlying pathology. These include basic metrics such as heart rate and QRS duration, but also more advanced biomarkers such as QRS microfragmentation (QRSµf) [1] and total cosine R to T (TCRT) [2] . In this work, we aimed to summarize all these markers derived from 12-lead standard ECGs into one novel risk score and evaluate its performance as mortality predictor in the emergency department. Methods We retrospectively collected 10- second 12- lead ECG recordings unselected patients presenting to the emergency department of a large university hospital between September 2019 and June 2022. For each patient a risk score was calculated from the first retrieved ECG using the criteria displayed in Figure 1. Calculation of all parameters was done as previously published. Patients with a total score of 0-1 points, 2-3 points, 4-6 points and 7 points were considered as low, intermediate, high and very high risk, respectively. The performance of the risk score was evaluated using Cox regression analysis and Kaplan-Meier curves with all-cause mortality within one year as primary endpoint. Results In total, 10 781 patients were included in our analyses. Median age was 69 (IQR 54-80) years, 5 588 (52%) were male and 5 193 (48%) were female. 6 966 (65%) patients were considered as low risk, 2 656 (25%) patients as intermediate risk, 1 098 (10%) patients as high risk and 61 (1%) patients as very high risk according to the ECG risk score with one year mortality rates of 8%, 17%, 26% and 43%, respectively (p < 0.001 for difference). In cox regression analysis the novel ECG risk score was a strong and independent predictor of one-year all-cause mortality with a hazard ratio of 1.35 (95% CI 1.31-1.39, p < 0.001). Kaplan-Meier survival curves for different risk categories are displayed in Figure 2. Conclusion In an unselected population of patients presenting to the emergency department of a large university hospital a novel risk score calculated from standard 12-lead ECGs recorded during clinical routine was a strong and independent mortality predictor. Further studies are needed to evaluate how incorporation of the novel score into existing triage systems can improve patient care.Figure 1:Calculation of ECG risk scoreFigure 2:Kaplan-Meier survival curves

Improved risk prediction in patients with atrial fibrillation and clinical intermediate-risk CHA2DS2VASc-score utilizing high sensitive troponin T

Abstract Background Guidelines of the European Society of Cardiology recommend risk assessment to identify appropriate candidates for anticoagulation in patients with atrial fibrillation (AF). However, scores such as the CHA2DS2VASc-score show only a modest performance for prediction of adverse events. Methods This retrospective single-center all-comer sub-study from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) enrolled 9,995 consecutive patients with non-valvular AF, presenting to the emergency department (ED) from June 2009 until March 2020. We tested the performance of the CHA2DS2VASc-score with and without high sensitive cardiac troponin T (hs-cTnT) for prediction of a adverse events such as stroke or major bleedings. Per CHA2DS2VASc, stroke risk was classified as low (0 point in men, ≤1 point in females), intermediate, or high (≥2 points in men and ≥3 points in females). Results Performance of the CHA2DS2VASc-score for the prediction of the composite endpoint consisting of stroke and major bleeding was poor (AUC 0.600, 95%CI: 0.590-0.610) but improved after addition of hs-cTnT as a variable across all risk categories (AUC 0.618 95%CI: 0.608-0.628, ∆AUC 0.0182 95%CI: 0.0124-0.0240, p<0.0001), and particularly in patients at intermediate-risk (∆AUC 0.160 95%CI: 0.0653-0.254, p=0.0009). The absence of detectable hs-cTnT (< LoD) identified a cohort without incident events within patients with intermediate per CHA2DS2VASc. Conclusion Combination of hs-cTnT and clinical-based risk stratification in AF patients presenting to an ED with intermediate CHA2DS2VASc-score is simple and effective. Measurement of hs-cTnT improves prediction of stroke risk in patients with intermediate CHA2DS2VASc-score and may help guide decision for or against anticoagulation.

AI-based algorithm for assessing coronary artery calcium score on contrast-enhanced cardiac computed tomography scans

Abstract Introduction In cardiac computed tomography (CT) examinations, non-contrast scans are often performed in addition to contrast-enhanced scans to quantify the coronary artery calcification (CAC) score. These calcium score scans are associated with additional exposure to ionizing radiation. Purpose We sought to develop a fully automated artificial intelligence (AI)-based algorithm capable of determining CAC score based solely on contrast-enhanced CT scans, eliminating the need for additional non-contrast scans. Methods An automated CAC scoring algorithm on contrast-enhanced CT scans was developed and trained using a dataset of 297 cardiac CT studies. Coronary artery calcifications were manually segmented in contrast-enhanced scans using a threshold of 2 standard deviations above the mean attenuation value of the ascending aorta. On non-contrast scans, CAC was manually assessed using a standard threshold of ≥130 Hounsfield Units. A correction factor for calcium score results assessed on contrast-enhanced scans was determined using linear regression. The algorithm was tested on an independent set of 90 contrast-enhanced CT scans (four manufacturers, eight scanner models). We compared automated CAC scores to manual expert reader reference assessments on non-contrast CT scans. CAC scores were categorized into four risk categories following the Society of Cardiovascular Computed Tomography recommendations: 0, 1-100, 101-300, and >300 Agatston Units. Results In the assessment of 90 CT studies (mean age 61.0±11.4 years, 46.7% males), the AI-model detected CAC in 69 contrast-enhanced scans (76.7%), comparable to the human reader's detection rate of CAC in 71 non-contrast scans (78.9%) (p = 0.63). The CAC score was initially calculated using AI-based segmentation of coronary calcification on contrast-enhanced scans and then the result was multiplied by established linear correction factor of 1.97. There was an excellent correlation between AI-model and manual reference total CAC scores (Pearson’s r = 0.96, 95% CI 0.94–0.97, p < 0.001). The model correctly classified 77 patients (85.6%) into the same CAC risk category as the human reader (Figure 1). Among 19 patients (21.1%) with a CAC score of zero, only 1 patient (5.3%) was reclassified with a non-zero CAC score by the AI-model. Cohen’s kappa value for CAC score risk categorization was 0.80 (p < 0.001), indicating very good agreement (Figure 2). Bland–Altman analysis revealed minimal bias of -9.7 Agatston Unit with 95% limits of agreement ranging from -184.8 to 165.5 Agatston Unit. Conclusions CAC score can be accurately quantified on contrast-enhanced cardiac CT scans using an automated AI-based algorithm. This approach has the potential to eliminate the necessity for an additional non-contrast CT scan, thereby reducing the patient's exposure to ionizing radiation.

A multicriteria decision-making model for risk management in an integrated management system

PurposeThis paper proposes a multicriteria model for risk management to identify and assess risks associated with an integrated management system (IMS). The main benefit of the proposed model is its systemic and logical visualization, which may facilitate the understanding of this proposal’s practical application.Design/methodology/approachThe research design consists of four stages: (1) conduct a literature review to establish risk management models in IMS; (2) collect data concerning risk management models in IMS from a large multinational automotive company; (3) propose a multicriteria model to define and assess risks as well as prioritize mitigation actions and (4) apply the proposed multicriteria model to the data collected in case-based research to evaluate the practical viability of the model to contribute to methods traditionally used.FindingsThe results showed that the proposed risk management model contributes to more reliable decision-making in an IMS. The application of the proposed model identified 85 risks in the total processes of the IMS, 31 of which were classified as high risk; thus, priority actions to be taken were defined. The risk classification and prioritization facilitated the implementation of measures to mitigate or eliminate risks, as pointed out by the company managers.Research limitations/implicationsOne of the limitations is the fact that specific knowledge is required to maintain and update the multicriteria decision-making tool used in this study. Another one implies the approach to managing risks under the different ISO standards and sector-specific requirements, since this may require updates and customization of the proposed risk management model.Practical implicationsThe implementation of IMS in contemporary business environments can be supported by a robust risk management approach. In addition, it provides the leadership with a holistic view of multiple aspects related to a company and fosters continuous improvement.Social implicationsThe social implications of this study are assessed indirectly. This study contributes to the improvement of company management models.Originality/valueTraditionally, the methods used for risk management in IMS are usually applied independently of techniques such as failure mode and effect analysis. The model developed in this work enables to manage risks continuously to achieve a systemic view of organizational issues and greater transparency of the processes.

Exercise intolerance at hospital discharge as a predictor for readmission and mortality after aortic aneurysm repair

Abstract Background As procedures of aortic aneurysm repair have advanced, an increased number of surgeries performed for older patients and those with comorbidities and low activities of daily living. Conversely, since these patients frequently suffer from difficulty returning to their daily activities after the surgery, physical function is considered an important indicator for risk classification and treatment effect evaluation. However, in patients following aortic aneurysm repair, the association between physical performance and clinical outcomes is not thoroughly evaluated. Purpose We aimed to clarify whether physical function at hospital discharge predicted clinical outcomes, including readmission rates and mortality, in patients following aortic aneurysm repair. Methods This was a single-centre cohort study. We included the patients admitted to a tertiary hospital to undergo surgery or endovascular repair for aortic aneurysm and who received cardiovascular rehabilitation during hospitalisation. As patient characteristics during hospitalisation, age, sex, body mass index (BMI), urgent or standby surgery, surgical type (open repair or endovascular), and comorbidities were obtained from medical records. We also reviewed 6-minute walk distance (6MWD) as physical function at hospital discharge, and 6MWD <300 m was defined as exercise intolerance. The primary and secondary endpoints were readmission and death for all causes, respectively. The multivariate Cox regression analysis was used to examine whether exercise tolerance predicted the endpoints. Results The 365 patients were studied for analysis. Exercise intolerance was observed in 107 patients (29.3 %). During the median follow-up period of 2.3 years, readmission and mortality for all causes occurred in 161 (44.1 %) and 39 (10.7 %), respectively. After adjusting for patient characteristics, including age, sex, BMI, urgent or standby surgery, and surgical type, exercise intolerance defined by 6MWD <300 m was significantly associated with higher mortality (adjusted hazard ratio [aHR]: 2.21, 95% confidence interval [CI]: 1.05–4.66, Figure 1-A) and readmission rates (aHR: 1.63, 95% CI: 1.13–2.34, Figure 1-B). Conclusions In patients following aortic aneurysm repair, exercise intolerance at hospital discharge independently predicted readmission and death for all causes. Our findings suggest that physical function after the aortic aneurysm repair is a useful predictor for patient risk classification and an indicator for treatment effect evaluation.

AI-enhanced detection of coronary inflammation predicts 10-year risk for cardiac mortality and MACE in individuals with no or minimal coronary atherosclerosis on routine CCTA

Abstract Background Coronary CT angiogram (CCTA) is one of the first line investigations for patients with chest pain suspected of coronary artery disease (CAD). Current CCTA interpretations mainly focus on luminal obstruction, which is identified in the minority of patients, whereas the majority who have no or minimal atherosclerotic plaques visible on CCTA are often provided with reassurance. However, residual risk from inflammation that drives atherosclerosis and plaque vulnerability are not captured with luminal stenoses alone. Fat attenuation index (FAI) Score quantifies coronary inflammation on routine CCTA, and integrate with clinical risk factors/plaque burden in an artificial intelligence enabled risk algorithm (AI-Risk) that could help to risk stratify this patient group. Purpose To evaluate the prognostic value or FAI Score and AI-Risk in the risk stratification of patients with no or minimal atherosclerosis. Methods In a nested cohort within the Oxford Risk Factors and Non-invasive imaging (ORFAN) study, consecutive patients (n=3,393) who underwent routine clinical CCTA were followed up over a median(IQR) 7.7(6.4-9.1) years for cardiac mortality and major adverse cardiac events (MACE, including myocardial infarction, new onset heart failure, cardiac mortality). CADRADS 2.0 classification 0 or 1 were used to define no or minimal luminal stenoses. FAI Score was calculated for each of the 3 epicardial coronary arteries. Results A total of 1,678 patients had no or minimal atherosclerosis on CCTA [median (IQR) age 53(45-63), 49.8% male]. Cardiac mortality occurred in 3.1% and MACE occurred in 8.8% of the patients during the follow-up period. Patients at the lowest quartile of FAI Score or low/medium AI-Risk classification showed very low event rate during follow up. Patients with the highest quartile of LAD FAI Score showed 9 times higher risk of cardiac mortality (Panel A) and 5 times higher risk of MACE (Panel B) compared to those at lowest quartile. Similar findings were observed for LCX and RCA. Finally, integrating coronary inflammation with clinical risk factors and plaque burden, patients at very high AI-Risk classification showed 5 times higher risk of cardiac mortality (Panel C), and 4 times higher risk of MACE (Panel D) compared to those with low/medium risk classification. Conclusion Coronary artery inflammation measured by FAI Score could stratify the risk of patients with no or minimal coronary atherosclerosis on CCTA, and could help to guide early preventative treatments.

Evaluation of naples prognostic score to predict long-term mortality in patients with pulmonary embolism

Abstract Background/Introduction APE mortality rates are still not satisfactory despite new diagnosis and treatment methods (1). Thus, risk classification is crucial due to the wide range of clinical presentations. Several risk stratifications have been developed such as simplified Pulmonary Embolism Severity Index (sPESI) (2). Nonetheless, there remains a need for an optimal indicator that can be conveniently measured with a high degree of precision to predict clinical outcomes. Naples prognostic score (NPS) is a newly defined index that is developed to determine the prognosis of cancer patients and reflects the inflammatory and nutritional status of the patients (3). Purpose The aim of our study was to determine the long-term prognostic value of NPS in APE patients. Methods Two hundred ninety-three patients diagnosed with APE between November 2016 and February 2022 were included in the study. NPS consists of 4 parameters: serum albumin, total cholesterol (TC) concentration, neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Naples scores of all patients were calculated and the patients were divided into 2 groups according to their NPS and their long-term mortality was compared. The primary endpoint of the study was long-term mortality. Results The long-term mortality was observed in 38 patients out of 293 patients in the mean follow-up of 24 (16-42) months. In the low-Naples risk group (group 1), there were 215 patients, while the high-Naples risk group (group 2) had 78 patients. Multivariate analysis showed that NPS as a categorical parameter (HR: 3.458, 95%CI:1.734-6.896, p<0.001), NPS as a numerical parameter, (HR:1.651, 95%CI:1.217-2.241, p=0.001) and simplified pulmonary embolism severity index (sPESI) (HR:1.887, 95%CI:1.223-2.911), p=0.004) score were independent predictors of long-term mortality. The receiver operating characteristic curve analysis showed that the model 2 with NPS as continuous had higher discriminative ability than the baseline model for detecting patients with mortality (Area under curve (AUC) values = 0.791 vs. 0.723, respectively, p=0.04) (Figure 1A). The long-term predictive capability of NPS was non-inferior than the sPESI score (Figure 1B). Conclusions The current study highlights that NPS, which reflects systemic inflammation and nutritional status may have potential to predict long-term mortality in APE patients. To our knowledge, this is the first study to show the relationship between long-term mortality and NPS in APE patients.

Adjustment of the SMART risk score by bioactive adrenomedullin enables a more accurate prediction of mortality in patients with ASCVD

Abstract Background Bioactive adrenomedullin 1-52 (bio-ADM) is a dynamic blood biomarker for real-time assessment of endothelial function. Bio-ADM was recently shown to be a prognostic marker in patients with acute heart failure and cardiogenic shock. The SMART (Second Manifestations of Arterial Disease) score is a validated tool for risk assessment in patients with established atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to assess whether measurement of bio-ADM adds incremental value to the SMART score in stable patients with ASCVD. Methods Circulating bio-ADM levels were assessed in n=695 stable patients with ASCVD in an all-comer cohort. Endpoints evaluated were all-cause mortality and cardiovascular mortality; follow up was 3 years. Results Bio-ADM was higher in non-survivors (all-cause death: n=54, median 33.1 pg/mL) compared to survivors (n=641, median 17.9 pg/mL; p<0.0001). Univariable Cox regression analyses showed bio-ADM to be associated with adverse outcome [standardized hazard ratio (HR) of bio-ADM values: All-cause death: 2.4, 95% confidence interval (CI): 2.0-2.9; p<0.001, cardiovascular death: 2.5, 95% CI: 1.9-3.3; p<0.001]. This association remained significant in various multivariable Cox regression models. Bio-ADM was found to be a strong marker for mortality (c-index: 0.80, Chi²: 54.1) and proved to be superior to other markers including hs-Troponin T (c-index: 0.61, Chi²: 2.0) and eGFR CKD-EPI 2021 (c-index: 0.687, Chi²: 33.5). Addition of bio-ADM to the SMART score significantly improved model performance in predicting mortality (SMART score: c-index: 0.717, Chi²: 24.73; SMART score + bio-ADM: c-index: 0.832, Chi²: 63.24; Delta c-index: 0.115; Delta Chi²: 38.51; all p<0.001) and showed net reclassification improvement in risk categorization with 11.6% in the group of survivors and 9.8% for non-survivors. Conclusion Bio-ADM provides incremental added value (improved discrimination, calibration and reclassification) on top of the SMART risk score in patients with ASCVD.

Classification of 90-day mortality risk among patients with cardiogenic shock requiring advanced mechanical circulatory support

Abstract Background The SCAI shock classification aims to provide a simple and practical stratification of the severity of patients with cardiogenic shock (CS) and to immediately offer them crucial treatments such as mechanical circulatory support (MCS). Additionally, the IABP shock II risk score is designed to predict 30-day mortality in patients with CS following acute coronary syndrome (ACS), and the SAVE score can also predict in-hospital mortality for patients after veno-arterial extracorporeal membrane oxygenation (V-A ECMO) insertion due to refractory CS. However, previous studies on SCAI staging in patients with MCS have been inconsistent, and the association with prognosis remains unclear. Purpose The aim of this study is to investigate the correlation between the SCAI shock stage and prognosis in ACS patients requiring advanced MCS, and to compare it with other prognostic scores. Methods From January 2012 to July 2023, 137 ACS patients with advanced MCS (excluding IABP) were evaluated. Upon ICU admission, patients were categorized into SCAI stages B to E. The IABP shock II score and the SAVE score were also calculated to serve as prognostic tools. The type of MCS was categorized as Impella, VA-ECMO with IABP, and ECPELLA (VA-ECMO with Impella). We compared the 90-day survival rates with the SCAI shock stage and other prognostic tools. Result The distribution for SCAI classifications stage B to E was 13 (10%), 38 (28%), 21 (15%), and 65 (47%), respectively. There were no significant differences among the groups regarding age, gender, comorbidities, the ratio of ST-elevation myocardial infarction, door-to-balloon time, and onset-to-reperfusion time. In SCAI Stage E, a significantly higher proportion of patients (86%) underwent extracorporeal cardiopulmonary resuscitation, exhibiting elevated lactate and peak CK-MB levels, along with higher IABP Shock II and lower SAVE scores, compared to other stages. A Kaplan-Meier analysis of 90-day mortality, based on the SCAI, the IABP Shock II, the SAVE categories, and the type of MCS, demonstrated that outcomes deteriorated as the stage advanced across all classifications. In the univariate Cox regression analysis for 90-day mortality, significant differences in outcomes were observed across the four classifications. However, in the multivariate Cox regression analysis that incorporated all four classifications, only the type of MCS (Impella vs. ECMO with IABP; hazard ratio [HR] 0.36; 95% confidence interval [CI], 0.16 - 0.78, p = 0.012) and the SCAI classification (stage E vs. stage C; HR 3.03; 95% CI, 1.51 - 6.08, p = 0.002) demonstrated a significant association with 90-day mortality. Conclusion The SCAI shock stage upon ICU admission suggests the potential for convenient prediction of mid-term outcomes in ACS patients who received advanced MCS.

Using the VES-13 score for risk stratification in outpatient heart failure management to predict mortality

Abstract Background We have previously demonstrated the efficacy of the Vulnerable Elders Survey-13 (VES-13) as a valuable tool for identifying frailty and predicting outcomes, such as mortality and hospitalisations, in heart failure (HF) outpatients when frailty is detected using a cut-off value of ≥3. Purpose This study aims to assess whether scores obtained from the VES-13, beyond its initial use with a frailty diagnosis threshold, enable a more precise categorization of mortality risk among heart failure outpatients. Methods Nurses administered the VES-13 during patients' initial consultations. We examined a sample of 331 patients, analyzing their main characteristics and individual VES-13 scores. VES-13 scores were categorized into quintiles for risk assessment. Results A total of 331 outpatients were prospectively included in the study. Patient characteristics were as follows: mean age of 69.85±11.96 years, 68% males, 67.6% in NYHA class II, and 25.7% in class III; ischemic aetiology was the most common (42%), and the mean left ventricular ejection fraction (LVEF) was 38.79±13.58. The VES-13 mean’s score was 2.67±2.81. Quintile 1 corresponded to a VES-13 score of 0, quintile 2 to score of 1, quintile 3 to score of 2, quintile 4 to scores of 3 or 4, and quintile 5 to a VES-13 score of 5 points or higher. During a follow-up period of 17.6±6.6 months (up to 24 months), 41 patients died (12.4%). After adjusting for sex, LVEF and ischemic aetiology stratifying VES-13 scores into quintiles allowed us to observe an accurate stratification of the risk of death with a statistically significant relationship between higher VES-13 quintiles and higher mortality (p=0.001) (Figure 1). Indeed, quintiles 4 and 5 were showed a very high hazard of risk of death compared to quintile 1 group (HR 6.97 [1.53, 31.65], p=0.012 for quintile 4; and HR 12.17 [2.77, 53.54], p=0.001 for quintile 5). Conclusions The VES-13, a standard screening tool in our heart failure clinic for identifying frailty, demonstrated the ability, when divided in quintile groups, of accurately stratify the risk of death over a follow-up period of up to two years.