Very-high Risk Research Articles

Abstract 4136273: A Machine Learning Approach to Simplify Risk Stratification of Patients with Atherosclerotic Cardiovascular Disease

Introduction: The 2018 AHA/ACC/Multisociety Blood Cholesterol Guideline recommends that patients with atherosclerotic cardiovascular disease (ASCVD) be classified as very high-risk (VHR) or not very high-risk (NVHR). This designation is based on the presence of > 2 major ASCVD events (recent acute coronary syndrome [ACS], history of myocardial infarction [MI], history of ischemic stroke, symptomatic peripheral artery disease [PAD]) or 1 major ASCVD event and > 2 high-risk conditions (age ≥65 years, heterozygous familial hypercholesterolemia, history of coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, persistently elevated LDL-cholesterol [LDL-C], history of heart failure). While this approach was initially instituted to better predict future ASCVD events alone, more intensive LDL-C lowering is now recommended for those at VHR (LDL-C treatment threshold of 55 mg/dL for VHR patients vs 70 mg/dL for NVHR patients). We aimed to simplify ASCVD risk stratification in patients with clinical ASCVD using machine learning models. Methods: We used electronic health record data (Providence Health system) from 2022 to identify patients with ASCVD based on ICD-10 codes. Patient demographics, comorbidities, and laboratory data stratified patients as VHR or NVHR. Then, a classification and regression tree analysis was performed, with the outcome being VHR classification. Patients were randomly assigned to either the testing or training dataset in equal proportion. Variables in the model included age, sex, race, ethnicity, and the Guideline criteria. Model performance was assessed using misclassification rate and area under the receiver operative curve (AUC). Results: A total of 491,514 patients with ASCVD were included, of which 56% were male, 77% were white, and the mean (SD) age was 72.5 (13.0) years. Over half of patients (59%) were VHR. Those with recent ACS, history of MI, history of ischemic stroke, or PAD were classified as VHR 93%, 92%, 84%, and 91%, respectively. Presence of hypertension in these patients increased the likelihood of being VHR to 97%, 97%, 94%, and 98%, respectively. The misclassification rate and AUC for the testing set were 6.8% and 96.2%, respectively. Conclusions: Most patients with a major ASCVD event and hypertension were found to be VHR. Relying on these two factors alone can help simplify risk assessment. This approach may also help increase use of guideline-recommended LDL-C lowering therapy.

Abstract 4115139: The Clinic Ottakring – Lipid Registry: a Contemporary Single-Center Real-World Analysis from a Tertiary Hospital

In the real world only about 20 % of patients with ASCVD are at the target range, as shown by the SANTORINI trial (1). Therefore, there is still a great need for the improvement of lipid-lowering therapy (LLT). Our Lipid Registry was set up as a retrospective study including patients who visited our outpatients ward focusing on lipid-lowering therapy (LLT). The indications were: low-density lipoprotein cholesterol (LDL-c) > 130 mg/dL in LLT- naive patients with acute coronary syndrome (ACS), coronary artery disease (CAD) not on optimal LLT, familial hypercholesterolemia and LLT intolerance. We collected baseline characteristics as well as laboratory parameters of these patients during their visits. The dual LLT (high-potency statin and ezetimibe) was initiated in every patient during the hospitalization, if not contraindicated, as target variable we used non-HDL-C. In total 181 patients were included, of which 136 (75.1%) patients visited our clinic for control purposes. Patients who didn’t visit the clinic were predominantly men and had no or few pre-experiences with LLT. Fourty-one (36.9%) patients had a BMI>30, 126 (92.6%) of patients had CAD of which 85 (63%) had the diagnosis of a recent ACS. Arterial hypertension was present in 78.7% and diabetes mellitus type 2 in 23.5% of cases. At the 1 st visit to our LLT department 4-6 weeks after dismission from the hospital, 86 patients (61.9%) reached the recommended (ESC/EAS 2019) non-HDL-C goal. At the 2 nd visit (8-12 weeks after index hospitalization), 117 patients (86.2%) and at the 3 rd visit 120 patients (88.2%) reached their target. The analysis of patients initially presenting with ACS showed that 60 (69.8%) of them after 4-6 weeks and 77 (90.6%) patients after 8-12 weeks reached the recommended non-HDL-c goal. Among the study population 108 (79.4%) of patients, and 81 (95.3%) of ACS patients received dual LLT immediately during the index event. After the first visit, 31 (36.5%) of ACS patients needed the addition of the third lipid-lowering drug to achieve the recommended goal (see attached tables). Our strategy for managing hyperlipidemia in patients with a very-high cardiovascular risk showed high achievement of the non-HDL-C goal as recommended by the recent ESC guidelines in contrast to real-world data. We were able to demonstrate, that the strategy based on the idea to treat high-CV risk patients early and strong is the way to reach the treatment goal in a high percentage of patients (2).

Prognostic role of lipoprotein(a) in atherosclerotic cardiovascular disease risk from a perspective on current risk stratification.

Lipoprotein(a) [Lp(a)] is an emerging predictor for atherosclerotic cardiovascular disease (ASCVD) but the association from a perspective on current risk stratification was unknown. A cohort of 9944 Chinese patients with ASCVD was recruited and refined into very-high-risk (VHR) and non-VHR subgroups according to current guideline. Lp(a) plasma levels were divided by its concentration (<30, 30-50, 50-75, and ≥75mg/dL) and percentile zones (<25th, 25-50th, 50-75th, 75-90th, ≥90th). Cardiovascular events (CVEs) occurred during an average of 38.5 months' follow-up were recorded. We found that Lp(a) was increased with risk stratification of ASCVD increasing. Prevalence of CVEs had a significantly increasing trend with gradients of Lp(a) elevation in VHR but not in non-VHR subgroup. The adjusted HRs (95%CIs) for CVEs were 1.75(1.25-2.46) in the highest group of Lp(a) ≥75mg/dL compared with the group of Lp(a)<30mg/dL as the reference in overall patients, 2.18(1.32-3.58) in VHR subgroup and 1.43(0.93-2.18) in non-VHR subgroup, respectively. The adjusted HRs (95%CIs) at the highest grade of Lp(a) levels (≥90th) were 1.72(1.19-2.50) in overall population, 2.83(1.53-5.24) in VHR subgroup and 1.38(0.86-2.12) in non-VHR subgroup, respectively. These findings suggested that Lp(a) might contribute more to CVEs risk in VHR subgroup of ASCVD.

A study to assess the ability of the HFA-ICOS risk stratification tool to predict cancer therapy-related cardiac dysfunction for patients receiving anthracycline chemotherapy

Abstract Introduction The use of anthracycline chemotherapy is complicated by the risk of developing cancer therapy-related cardiac dysfunction (CTRCD). The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) have jointly published a novel cardiovascular risk stratification tool for patients receiving anthracycline chemotherapy which categorises patients according to their risk of CTRCD (1). The risk tool has not yet been validated for use in the United Kingdom. Purpose In this study, we test the ability of the HFA-ICOS risk stratification tool to predict CTRCD for patients receiving anthracycline chemotherapy. Methods A retrospective study of patients ≥18 years who received anthracycline chemotherapy between January 2019 to January 2023 at two cardio-oncology centres in the United Kingdom. Patients were eligible if they had ≥1 follow up echocardiogram after the end of anthracycline treatment. Patients receiving HER-2 targeted therapies were excluded. Patients were classified into low/medium/high/very-high risk categories using the HFA/ICOS tool. The prevalence of CTRCD was assessed during the follow up period; a minimum of 6 months after the end of chemotherapy. Results 288 patients met eligibility criteria for the study. 59 patients (20%) were treated for leukaemia, 104 (36%) lymphoma, 63 (22%) sarcoma and 49 (17%) breast cancer. The mean age was 49±18yrs, with 56% females. The mean cumulative dose of doxorubicin (or equivalent) was 235±104mg/m2. Using the HFA/ICOS tool, 50% of patients were deemed low risk, 31% medium risk, 16% high risk and 3% very high risk at baseline. Using guideline recommended CTRCD definitions, there was an overall incidence of 9% of symptomatic CTRCD and 22% of asymptomatic CTRCD (Table 1). The incidence of symptomatic CTRCD significantly increased as the baseline risk of CTRCD increased. 20% of patients deemed high or very-high risk at baseline subsequently developed symptomatic CTRCD (Fig 1). Furthermore, patients at high or very-high risk were 4.4 times more likely to develop symptomatic CTRCD than patients who were low risk (OR 4.4, 95% CI 1.7-11.6, p=0.003). There was no association with baseline risk and the development of asymptomatic CTRCD. The incidence of mild asymptomatic CTRCD may be underestimated due to the lack of routine surveillance with cardiac biomarkers and left ventricular global longitudinal strain (LV GLS) imaging for asymptomatic disease during the study period. Conclusion The novel HFA/ICOS risk stratification tool is useful in predicting patients who will develop symptomatic CTRCD in a contemporary UK setting.

Cardiovascular prevention with GLP1 agonists in high or very-high cardiovascular risk irrespective of diabetes

Abstract Introduction Patients with established cardiovascular disease have an increased risk of stroke and myocardial infarction, even in the absence of atrial fibrillation. Several trials have analyzed the effect of glucagon-like peptide-1 receptor (GLP1) agonists in patients with high cardiovascular risk and lately this effect has been studied even in the absence of diabetes. Methods A meta-analysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The primary objective of the study was to analyze the composite endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (MACE). As secondary objectives, cardiovascular death, non-fatal myocardial infarction and non-fatal stroke have been studied separately. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. In the case of significant heterogeneity in the primary objective, a stratified analysis with exposure time have been performed to explain this outcome. Results A sum of 9 randomized controlled trials were included where a GLP1 agonist such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide was compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonist. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes and 60552 (77.9%) from cardiovascular disease. As showed in figure 1, the GLP1 agonists showed a reduction of 13% of the MACE (RR: 0.87, 95% CI 0.81-0.92; p&amp;lt;0.001). Heterogeneity could be explained by exposure time and concentration in the blood, considering that it disappears within each group when applying this condition. Treatment with GLP1 agonist also reduced cardiovascular death by 12% (RR: 0.88, 95% CI 0.82-0.94; p&amp;lt;0.001), non-fatal strokes by 14% (RR: 0.86, 95%CI 0.79-0.95; p&amp;lt;0.001) and non-fatal miocardial infarction by 13% (RR: 0.87, 95% CI 0.78-0.97; p&amp;lt;0.001). Conclusion Treatment with a GLP1 agonist reduced the incidence of the MACE by 13% and cardiovascular death by 12%, as well as it decreased the incidence of nonfatal stroke by 14% and of nonfatal myocardial infarction by 13% in different RCTs involving patients with high or very-high cardiovascular risk with or without diabetes.

Redefining cardiovascular risk evaluation: employing the CaRi-Heart validated FAI-score in patients screened with SCORE2 and CAD-RADS 2.0 techniques

Abstract Background Cardiac computed tomography (CCT) has confirmed the fat attenuation index (FAI) as a trustworthy marker for coronary inflammation, notably in relation to plaque vulnerability and progression. The systematic coronary risk evaluation 2 (SCORE2) is a valuable instrument for forecasting the 10-year likelihood of initial cardiovascular disease (CVD) occurrence. This study aims to determine risk re-categorization using CaRi-Heart in comparison to SCORE2 and the coronary artery disease-reporting and data system (CAD-RADS 1.0/2.0). Methods We enrolled patients (INTEL-FAT study) undergoing CCT, who were aged 40-69 years and had no previous history of CVD or diabetes. SCORE2 classified very-high-risk regions as follows: low-moderate risk as &amp;lt;2.5% (&amp;lt;50 years) and &amp;lt;5% (50-69 years), high risk as 2.5 to &amp;lt;7.5% (&amp;lt;50 years) and 5 to &amp;lt;10% (50-69 years), and very-high risk as ≥7.5% (&amp;lt;50 years) and ≥10% (50-69 years). The CaRi-Heart risk assessment categorized low risk as FAI-score ≤75th percentile for the LAD or RCA and &amp;lt;95th percentile for the LCX; medium risk as falling between the 76th and 89th percentiles for LAD/RCA and ≥95th percentile for LCX; and high risk as ≥90th percentile for LAD/RCA. Results 203 patients were included, with a mean age of 58.7 ± 6.78; 143 (70.44%) were male. CaRi-Heart assessment redefined 71.13% (69/97) of individuals from high to low SCORE2 risk, and 40.0% (8/30) from low-moderate to high SCORE2 risk. The weighted Cohen's kappa analysis revealed minimal concordance between SCORE2 and CaRi-Heart (k=-0.043). 19.71% of patients categorized as CAD-RADS 1 in CCT were reassigned to high risk after CaRi-Heart evaluation, and 26.66% of those classified as CAD-RADS 4 were downgraded to low risk. Furthermore, of the CAD-RADS 1 P1/P2 group, 15.38% and of the P3/P4 group, 66.66% were upgraded to high risk. Conversely, 45.45% of CAD-RADS 4 P1/P2 and 15.78% of P3/P4 were reassigned to low CaRi-Heart risk. The Cohen's kappa analysis comparing CAD-RADS 1.0 and 2.0 with CaRi-Heart risk revealed a low concordance (k=0.067 and k=0.014). In comparing SCORE2 risk categories to CAD-RADS classifications, a significant association was found for low-moderate SCORE2 with CAD-RADS 2 (diagnostic odds ratio [DOR] of 11.26; 95% CI: 4.37-29.00; p&amp;lt;0.001), and for high SCORE2 with CAD-RADS 4 (DOR: 0.085; 95% CI: 0.036-0.20; p&amp;lt;0.001), indicating a strong predictive value of the SCORE2 system for certain CAD-RADS classifications. Conclusions The CaRi-Heart method significantly alters risk classifications in comparison to the SCORE2 risk assessment models or the anatomical CAD-RADS 1.0 and 2.0 diagnostic instruments. These results indicate the importance of integrating established scoring systems with additional markers, such as the FAI-score. This integration offers critical understanding into the severity and future course of CAD, assisting in risk stratification and informing therapeutic choices.SCORE2, CAD-RADS and CaRi-Heart risk.Interpretation of the CaRi-Heart® risk.

Lipid management among very-high-risk patients with atherosclerotic cardiovascular disease and type 2 diabetes

Abstract Background Patients with established atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (DM2) often meet very-high-risk (VHR) criteria for recurrent ASCVD events and are recommended for aggressive low-density lipoprotein-cholesterol (LDL-C) lowering in guidelines. Purpose Our study aimed to evaluate the proportion of patients achieving guideline-based lipid goals and identify factors associated with achieving these goals among VHR patients with established ASCVD and DM2. Methods Electronic health record data were used to identify VHR patients with established ASCVD and DM2 across 14 large US healthcare systems between 1/1/2022-12/31/2022 with an available LDL-C measurement. We examined the percentage of patients achieving guideline-based lipid goals based on the 2018 AHA/ACC Multisociety Guideline, defined as either having an LDL-C &amp;lt;70 mg/dL or receiving maximal lipid-lowering therapy (i.e., on a PCSK9i monoclonal antibody (mAb)) at the time of the last LDL-C test, and performed multivariable logistic regression to evaluate factors associated with the achievement of those goals. Results Among 213,380 eligible VHR patients with ASCVD and DM2 (mean age 70.2 years, 42% women), 51.8% (110,452) patients achieved guideline-based lipid goals. This included 50.9% with an LDL-C &amp;lt;70 mg/dL and 1.7% on a PCSK9i mAb. Female sex (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.61-0.66), Black race (OR, 0.67; 95% CI, 0.63-0.72), Medicaid insurance (OR, 0.92; 95% CI, 0.86-0.97), and non-coronary artery disease forms of ASCVD including peripheral artery disease (OR, 0.67; 95% CI, 0.65-0.69) and cerebrovascular disease (OR, 0.80; 95% CI, 0.77-0.83) were associated with a lower likelihood of achieving guideline-based lipid goals. Conversely, having undergone percutaneous coronary intervention (OR, 1.31; 95% CI, 1.19-1.43) or coronary artery bypass graft (OR, 1.24; 95% CI, 1.06-1.45) in the previous year, and comorbidities including dialysis (OR, 1.38; 95% CI, 1.23-1.55), atrial fibrillation or flutter (OR, 1.09; 95% CI, 1.06-1.12), and systolic heart failure (OR, 1.11; 95% CI, 1.08-1.14) were associated with a higher likelihood of achieving these goals. Overall, 24.0% of patients were on no statin, 27.2% were on a low- or moderate-intensity statin, and only 5.8% were on a statin in combination with ezetimibe or a PCSK9i mAb. Conclusion Large gaps in care exist for VHR patients with ASCVD and DM2, particularly among women, Black individuals, and those with Medicaid. Targeted interventions are needed to improve the uptake of evidence-based secondary prevention therapies in these patients.

Contemporary LDL-cholesterol management in male and female patients at high-cardiovascular risk: results from the European observational SANTORINI study

Abstract Background Middle aged women have a faster increase in atherosclerotic cardiovascular disease (ASCVD) events than men over time. Undertreatment with guideline-recommended therapy in women may be one of the drivers for this burden. Purpose To compare high- or very high-risk male and female patients regarding contemporary 1-year low-density lipoprotein cholesterol (LDL-C) goal attainment, lipid-lowering therapy (LLT) intensity, and major adverse cardiovascular event (MACE) rate. Methods SANTORINI is an observational, prospective study that enrolled high- and very high-cardiovascular risk patients between March 2020 and Feb 2021, across 623 sites and 14 countries in Europe from primary &amp; secondary care settings, with a further 1-year prospective follow-up. We included all patients with an LDL-C measurement at baseline and 1-year follow up (1yFU) for the current analysis. LDL-C goal attainment was defined separately for high and very-high risk categories according to 2019 ESC/EAS guidelines. Results Overall, 5197 males with a mean age of 65 years, and 2013 females with a mean age 66 years were included. At baseline, male patients had higher prevalence of pre-existing ASCVD (81.6% vs. 63.5%), and a lower prevalence of familial hypercholesterolaemia (8.7% vs. 17.2%) than female patients (Table 1). The proportion of patients reaching LDL-C goal improved from baseline to 1yFU, but was greater in males (22.9% and 33.3%, respectively) than females (16.9% and 24.6%, respectively). Similarly, the proportion of patients receiving no LLT decreased from baseline to 1yFU for both sexes, however, more females than males received no LLT at 1yFU (male: 20.7% to 2.7%; female: 23.9% to 3.9%). High intensity statin use increased for both sexes but was higher for males (22.2% to 27.3%) than for females (15.5% to 19.5%) at 1yFU. By contrast, PCSK9i use at baseline and 1yFU was lower for males (6.6% to 9.3%) than for females (9.8% to 13.4%). Nevertheless, the use of combination LLT at 1yFU was lower among females than males (male: 27.8% to 42.2%; female: 26.7% to 40.2%). During follow-up, MACE-4 was higher in males (5.31/100 patient years [PY]; 95% confidence interval [CI]: 4.68–5.95) than in females (3.63/100PY; 95% CI: 2.79–4.47). Similar results were observed for MACE-3 (Table 2). Conclusions Despite similar guideline recommendations, use of combination LLT and high intensity statin therapy was lower in female patients at high or very high cardiovascular risk than in male patients over one year of follow-up. Accordingly, female patients had lower LDL-C goal attainment both at baseline and at one-year. Nevertheless, due to intrinsic risk factors, female patients had lower rates of MACE-4 and MACE-3 than male patients.

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score &amp;gt; 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC &amp;gt; zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p&amp;lt; 0.001) as well as between those with CAC ≥ 100 and those with CAC score &amp;lt; 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p&amp;lt;0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p&amp;lt;0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p&amp;lt; 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p&amp;lt;0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

Comparative characteristics and invasive management in patients with non-ST elevation acute coronary syndromes in two high-volume hospitals from Romania and Germany

Abstract Introduction Cardiovascular disease (CVD) carries the highest mortality burden across Europe, acute coronary syndromes (ACS) being responsible for most CVD-related deaths. However, significant regional differences in ACS management have been reported. Purpose To describe the characteristics and management of patients with higher-risk non-ST elevation ACS (NSTE-ACS) in 2 high-volume hospitals from 2 European countries with different prevalence of CVD and different income (Germany – GER and Romania – RO). Methods All consecutive invasively managed high and very-high risk NSTE-ACS patients admitted in 2022 in two high-volume hospitals from GER and RO were identified. Patient clinical profiles, coronary anatomy, revascularization strategies, and in-hospital outcomes were compared. Results were adjusted for age and gender. Results 707 patients (345 GER, 66.7% male; 362 RO, 71.5% male; p&amp;gt;0.05) were included. RO patients were younger (65.5 vs. 70.1 years), with higher rates of hypertension (88.7% vs. 82.0%), dyslipidemia (95.6% vs. 81.7%), diabetes (46.1% vs. 34.5%), and active smoking (37.3% vs. 23.5%) (all p&amp;lt;0.05); whereas GER patients had higher rates of atrial fibrillation (36.2% vs. 23.2%), chronic respiratory disease (24.6% vs. 10.5%), sleep apnoea (9.0% vs. 1.4%), thyroid disorders (24.1% vs. 6.4%), and prior revascularization by percutaneous coronary interventions (PCI) (36.5% vs. 20.2%) or coronary artery bypass grafting (CABG) (15.7% vs. 3.0%) (all p&amp;lt;0.05). Mean left ventricular ejection fraction (LVEF) was lower in the RO cohort (43.4% vs. 48%, p&amp;lt;0.001). Rates of myocardial infarction diagnosed by high-sensitivity troponin I assays (88.7% GER, 87.6% RO), and median diagnosis-to-cathlab intervals (12.8 hours GER, 15.5 hours RO) were similar (all p&amp;gt;0.05). In the obstructive coronary artery disease (CAD) group (80.3% GER, 84.3% RO), no differences were found in multivessel disease rates (67.1% GER, 69.8% RO) or mean SYNTAX score (18.6 GER, 16.9 RO) (all p&amp;gt;0.05). For type 1 NSTE-ACS (67% GER vs. 79% RO, p&amp;lt;0.001), PCI represented the main revascularization method (88.3% GER vs. 78.3% RO, p&amp;lt;0.05). Excluding patients with prior CABG undergoing PCI, complete revascularization (residual SYNTAX score ≤8), was reported in 77.1% GER and 84.4% RO of the PCI cases (p&amp;gt;0.05). Intravascular imaging was used in 28.4% of PCIs in GER, and in none in RO. In-hospital mortality (7.0% GER, 6.8% RO), and rates of major adverse cardiovascular events, defined as a composite of death, myocardial infarction, and stroke (8.1% GER, 9.1% RO), were similar (all p&amp;gt;0.05). Conclusions Higher-risk NSTE-ACS patient profiles mirror overall country CVD risk patterns. Compared to Germany, patients in Romania are younger, with a higher CVD risk factor burden, lower LVEF, underdiagnosis of major non-CVD comorbidities, and delayed CAD diagnosis. Despite similar guideline-directed management and in-hospital outcomes in both centres, these aspects may influence the long-term prognosis.

PPP03 Presentation Time: 10:48 AM: Treatment Outcomes of External Beam Radiotherapy, Brachytherapy Boost and Androgen Deprivation Therapy with or without Chemotherapy for Very-High Risk Non-Metastatic Prostate Cancer Patient

PPP03 Presentation Time: 10:48 AM: Treatment Outcomes of External Beam Radiotherapy, Brachytherapy Boost and Androgen Deprivation Therapy with or without Chemotherapy for Very-High Risk Non-Metastatic Prostate Cancer Patient

Association Between Measurable Residual Levels and Infection Mortality in Acute Myeloid Leukemia

Abstract Background Acute myeloid leukemia (AML) outcomes have improved over the years. Better AML disease risk classification, achieved by measuring minimal residual disease (MRD) levels, has contributed to improved treatment and survival. Even though the role of MRD in survival is still preliminary, results are promising. However, infections are still a problem to circumvent. In our previous protocol LMA-GATLA 2007 we found a 30% incidence of sepsis related death (SRD), and they were more frequent during or after first induction. The overall survival of that study was 51.4 % (0.38). In this study, we aimed to analyze the mortality rates due to infection; and determine if there is an association of the MRD levels and infection mortality rates; also, we will analyze overall outcomes of AML. Methods Patients were accrued form the National Registry GATLA LMA 2021 protocol. Disease risks were classified based on cytogenetics and molecular abnormalities as standard risk (SR), high risk (HR), and very high risk (VHR). MRD determinations were performed using flow cytometry after 1st induction with mitoxantrone, anthraciclines and etoposide (MAE) protocol, at day 22 and 29 and after 2nd induction with high dose citarabine and mitoxantrone (HAM). We used descriptive statistics (analysis by frequency), compared categorical variables using chi-square or χ2 test and Fisher test, and time to event calculation techniques. Results 95 patients have been accrued, 51.6 % were males. The median age was 9 years of age (IQR 3-13), and 31% were SR, 22% HR, and 47% VHR. MRD levels &amp;lt; 0.1% were seen in 55.5% post first induction, 92% post intensification and 85% post consolidation. Estimated probability of overall survival was 65% (ES 0.6) at 45.7 (2.7) months, (CI 95% 40.3-51,1). 23 pts (24%) died; 11 (48 %) for progression, 7 (30%) for sepsis, for non-sepsis toxicity 3 (13%), other causes 2 pts (9%). Hazard ratio of death with MRD &amp;gt; 0.1% was 2.35 (p=0.06, 95% CI 0.043-1.756). The incidence of SRD was 7.4%, 4 patients had sepsis with MRD &amp;lt; 0.1% (57 %), after HAM /consolidation phase; and 3 patients with &amp;gt; 0.1% (43%) when in relapse (p= 0.028). The SRD episodes were independent from MRD levels, however patients on remission showed SRD as late events, because no patient developed SRD during or after first induction. Conclusion Overall survival results have improved with current protocol. MRD seems a valuable tool to estimate response, levels &amp;gt;0.1 % are associated with increased risk of death. However, better infection prevention and care are required to improve further the outcomes, especially those associated with higher MRD levels.

Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study.

MYC/MYCN are the most frequent oncogene amplifications in medulloblastoma (MB) and its primary biomarkers of high-risk (HR) disease. However, while many patients' MYC(N)-amplified tumors are treatment-refractory, some achieve long-term survival. We therefore investigated clinicobiological heterogeneity within MYC(N)-amplified MB and determined its relevance for improved disease management. We characterized the clinical and molecular correlates of MYC- (MYC-MB; n = 64) and MYCN-amplified MBs (MYCN-MB; n = 95), drawn from >1600 diagnostic cases. Most MYC-MBs were molecular group 3 (46/58; 79% assessable) and aged ≥3 years at diagnosis (44/64 [69%]). We identified a "canonical" very high-risk (VHR) MYC-amplified group (n = 51/62; 82%) with dismal survival irrespective of treatment (11% 5-year progression-free survival [PFS]), defined by co-occurrence with ≥1 additional established risk factor(s) (subtotal surgical-resection [STR], metastatic disease, LCA pathology), and commonly group 3/4 subgroup 2 with a high proportion of amplified cells. The majority of remaining noncanonical MYC-MBs survived (i.e. non-group 3/group 3 without other risk features; 11/62 (18%); 61% 5-year PFS). MYCN survival was primarily related to molecular group; MYCN-amplified SHH MB, and group 3/4 MB with additional risk factors, respectively defined VHR and HR groups (VHR, 39% [35/89]; 20% 5-year PFS/HR, 33% [29/89]; 46% 5-year PFS). Twenty-two out of 35 assessable MYCN-amplified SHH tumors harbored TP53 mutations; 9/12 (75%) with data were germline. MYCN-amplified group 3/4 MB with no other risk factors (28%; 25/89) had 70% 5-year PFS. MYC(N)-amplified MB displays significant clinicobiological heterogeneity. Diagnostics incorporating molecular groups, subgroups, and clinical factors enable their risk assessment. VHR "canonical" MYC tumors are essentially incurable and SHH-MYCN-amplified MBs fare extremely poorly (20% survival at 5 years); both require urgent development of alternative treatment strategies. Conventional risk-adapted therapies are appropriate for more responsive groups, such as noncanonical MYC and non-SHH-MYCN MB.

Survival of Children with Acute Lymphoblastic Leukemia with Risk Group-Based Protocol Changes: A Single Center Experience with 460 Patients over a 20-Year Period.

Recent treatments for pediatric acute lymphoblastic leukemia (ALL) are founded on risk stratification. We examined the survival rates and prognostic factors of patients over a 20-year period at a single institution. This study analyzed patients diagnosed with ALL and treated at the Pediatric Department of Samsung Medical Center (SMC). Patients were categorized into standard-risk (SR), high-risk (HR), and very high-risk (VHR) groups. The SMC protocol for the HR group underwent two changes during the study period: A modified Children's Cancer Group (CCG)-1882 protocol was used from 2000 to 2005, the Korean multicenter HR ALL-0601 protocol from 2006 to 2014, and the Korean multicenter HR ALL-1501 protocol from 2015 to 2019. Of the 460 patients, complete remission was achieved in 436 patients (94.8%). The 10-year overall survival rate (OS) was 83.8±1.9% for all patients. OS according to the SMC risk group was as follows: 95.9±1.4% in the SR group, 83.8±3.6% in the HR group, and 66.2±6.9% in the VHR group. The 5-year OS within the HR group varied according to the treatment protocol: 73.9±7.5%, in the modified CCG-1882 protocol, 83.0±3.9%, in the 0601 protocol, and 96.2±2.6%, in the 1501 protocol. For those aged 15 years and older, the OS was only 56.5±13.1%. Relapse occurred in 71 patients (15.4%), and the OS after relapse was 37.7±6.0%. The treatment outcomes of patients with ALL improved markedly. However, there is a need to further characterize adolescents and young adult patients, as well as those who have experienced relapses.

Outcome of 421 adult patients with Philadelphia-negative acute lymphoblastic leukemia treated under an intensive program inspired by the GIMEMA LAL1913 clinical trial: a Campus ALL study.

The introduction of pediatric-inspired regimens in adult Philadelphia-negative acute lymphoblastic leukemia (Ph-ALL) has significantly improved patients' prognosis. Within the Campus ALL network we analyzed the outcome of adult Ph-ALL patients treated according to the GIMEMA LAL1913 protocol outside the clinical trial, to compare the real-life data with the study results. We included 421 consecutive patients, with a median age of 42 years. The complete remission (CR) rate after the first course of chemotherapy was 94% and a measurable residual disease (MRD) negativity after the third course was achieved in 72% of patients. The 3-year overall survival (OS) and disease-free survival (DFS) were 67% and 57%, respectively. In a multivariate analysis, MRD positivity negatively influenced DFS. In a time-dependent analysis including only very high risk (VHR) and MRD positive cases, transplanted (HSCT) patients had a significantly better DFS than non-HSCT ones (P=0.0017). During induction, grade ≥2 pegaspargase-related hepato-toxicity was observed in 25% of patients (vs 12% in the GIMEMA LAL1913 trial, P=0.0003). In this large real-life cohort of Ph-ALL, we confirmed the very high CR rate and a superimposable OS and DFS compared to the GIMEMA LAL1913 clinical trial: CR rate after C1 94% vs 85%, P=0.0004; 3-year OS 67% vs 67%, P=0.94; 3-year DFS 57% vs 63%, P=0.17. HSCT confirms its important role in VHR and MRD-positive patients. The rate of pegaspargase-related toxicity was significantly higher in the real-life setting, emphasizing the importance of dose adjustment in the presence of risk factors to avoid excessive toxicity.

Prognostic significance of residual tumor at restaging transurethral bladder resection in high-risk non-muscle-invasive bladder cancer.

To assess prognostic significance of residual tumor at repeat transurethral resection (reTUR) in contemporary non-muscle-invasive bladder cancer (NMIBC) patients. Patients were identified retrospectively from eight referral centers in France, Italy and Spain. The cohort included consecutive patients with high or very-high risk NMIBC who underwent reTUR and subsequent adjuvant BCG therapy. A total of 440 high-risk NMIBC patients were screened, 29 (6%) were upstaged ≥ T2 at reTUR and 411 were analyzed (T1 stage: n = 275, 67%). Residual tumor was found in 191 cases (46%). In patients with T1 tumor on initial TURBT, persistent T1 tumor was found in 18% of reTUR (n = 49/275). In patients with high-grade Ta tumor on initial TURBT, T1 tumor was found in 6% of reTUR (n = 9/136). In multivariable logistic regression analysis, we found no statistical association between the use of photodynamic diagnosis (PDD, p = 0.4) or type of resection (conventional vs. en bloc, p = 0.6) and the risk of residual tumor. The estimated 5-yr recurrence and progression-free survival were 56% and 94%, respectively. Residual tumor was significantly associated with a higher risk of recurrence (p < 0.001) but not progression (p = 0.11). Only residual T1 tumor was associated with a higher risk of progression (p < 0.001) with an estimated 5-yr progression-free survival rate of 76%. ReTUR should remain a standard for T1 tumors, irrespective of the use of en bloc resection or PDD and could be safely omitted in high-grade Ta tumors. Persistent T1 tumor at reTUR should not exclude these patients from conservative management, and further studies are needed to explore the benefit of a third resection in this subgroup.

Adjuvant Everolimus in Non–Clear Cell Renal Cell Carcinoma

Clinical trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant. To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC. This prespecified subgroup analysis of a phase 3 randomized clinical trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016. Eligible patients had fully resected RCC at intermediate-high risk (pT1 grade 3-4, N0 to pT3a grade 1-2, N0) or very-high risk (pT3a grade 3-4 to pT4 any grade or N+) for recurrence who had received radical or partial nephrectomy. Final analyses was completed in March 2022. The intervention group received 54 weeks of everolimus (10 mg orally daily); the control group received a matching placebo. The main outcomes were RFS, OS, and rates of adverse events. For testing the hazard ratio (HR) for treatment effect, a Cox regression model was used for both OS and RFS. Of 1545 adult patients with treatment-naive, nonmetastatic, fully resected RCC in EVEREST, 109 had papillary RCC (median [range] age, 60 [19-81] years; 82 [75%] male; 50 patients [46%] with very high-risk disease) and 99 had chromophobe RCC (median [range] age 51 [18-71] years; 53 [54%] male; 34 patients [34%] with very high-risk disease). Among 57 patients with papillary RCC in the intervention group, 26 (46%) completed 54 weeks of treatment, and among 53 patients with chromophobe RCC in the intervention group, 26 (49%) completed 54 weeks of treatment. With a median (IQR) follow-up of 76 (61-96) months, adjuvant everolimus did not improve RFS compared with placebo in either papillary RCC (5-year RFS: 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P = .61) or chromophobe RCC (5-year RFS: 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P = .79). In the combined non-clear RCC cohort, grade 3 or higher adverse events occurred in 48% of patients who received everolimus and 9% of patients who received placebo. In this clinical trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the study do not support adjuvant everolimus for this cohort. However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out. ClinicalTrials.gov Identifier: NCT01120249.

Attainment of LDL-cholesterol target in high cardiovascular risk type 1 diabetic French people

AimsAs people with type 1 diabetes have increased risk of cardiovascular morbi-mortality, management of cardiovascular risk factors is of crucial importance. We assessed the prevalence and factors associated with LDL-cholesterol (LDL-c) target achievement in patients with type 1 diabetes at high and very-high cardiovascular risk. MethodsIn this observational multicenter study, we included hospitalized patients with type 1 diabetes who had a fasting blood lipid analysis at admission. Cardiovascular risk level and LDL-c target values were defined according to ESC/EAS guidelines into force at admission: LDL-c target for very-high risk (VHR) and high risk (HR) patients was 1.4 and 1.8 mmol/l respectively for patients included from September 2019 (2019 guidelines) and 1.8 and 2.6 mmol/l respectively for patients included in 2016–2019 (2016 guidelines). LDL-c target attainment was assessed in HR and VHR patients, and factors associated with attainment were identified with multivariable analysis. ResultsWe included 85 HR patients (median age 37y [interquartile range: 27;45], 64 % females) and 356 VHR patients (49 [35;61] years, 42 % females). In HR patients, 7 % were treated with statins, and 35.3 % achieved the LDL-c target. Increasing age (odds ratio 0.58 [95 % confidence interval: 0.38;0.89]), body mass index (0.86 [0.75;0.98]), and HbA1c (0.69 [0.50;0.94]) were independently associated with lower odds of attaining LDL-c target. In VHR patients, 36 % were treated with statins, and 17.4 % achieved LDL-c target. Statin treatment (2.33 [1.22;4.43]), secondary prevention (2.33 [1.21;4.48]) and chronic renal failure (2.82 [1.42;5.61]) were associated with higher odds of attaining LDL-c target. ConclusionControl of LDL-c is highly insufficient in both HR and VHR patients. Cardiovascular risk evaluation and better control of risk factors may help decrease cardiovascular morbi-mortality in patients with type 1 diabetes. Registration numberNCT03449784.

Seismic Risk Assessment in School Buildings: A Comparative Study of Two Assessment Methods

Seismic risk assessment in school buildings is critical for ensuring the safety and resilience of educational institutions against seismic events. This paper presents a new seismic risk methodology named MM Risk and comparative study with Adriseismic methodology used for seismic risk assessment. The study aims to provide insights into the effectiveness and reliability of these methods in evaluating the seismic vulnerability of school buildings. Through a comprehensive review of the existing literature and application on a dataset of 213 schools (367 buildings), this paper evaluates the strengths and limitations of each method in terms of accuracy, complexity, and practical applicability. The results show that by integrating the approach of Adriseismic methodology and incorporating extensions related to irregularities, the social risk component (number of users), and the ability to assess different types of structures, a comprehensive and tailored methodology for assessing seismic risk can be developed. This is important since these factors are strongly influencing the seismic risk of schools as connected systems. Furthermore, this paper explores the implications of these findings for improving seismic risk mitigation strategies in school buildings. MM Risk methodology places over 70% of school buildings in the medium seismic risk category and 27% in the high seismic risk category. On the other hand, the Adriseismic methodology is more stringent, classifying 60% of school buildings into high and very-high risk categories. This disparity undoubtedly influences the prioritization list for seismic risk mitigation measures. However, definitely the comparative analysis presented in this paper offers valuable guidance for engineers, policymakers, and stakeholders involved in the seismic retrofitting and design of school buildings, ultimately contributing to the enhancement of seismic resilience in educational infrastructure.

Real-world evidence evaluation of LDL-C in hospitalized patients: a population-based observational study in the timeframe 2021–2022

AimsEuropean registries and retrospective cohort studies have highlighted the failure to achieve low-density lipoprotein-cholesterol (LDL-C) targets in many very high-risk patients. Hospitalized patients are often frail, and frailty is associated with all-cause and cardiovascular mortality. The aim of this study is to evaluate LDL-C levels in a real-world inpatient setting, identifying cardiovascular risk categories and highlighting treatment gaps in the implementation of LDL-C management.MethodsThis retrospective, observational study included all adult patients admitted to an Italian hospital between 2021 and 2022 with available LDL-C values during hospitalization. Disease-related real-world data were collected from Hospital Information System using automated data extraction strategies and through the implementation of a patient-centered data repository (the Dyslipidemia Data Mart). We performed assessment of cardiovascular risk profiles, LDL-C target achievement according to the 2019 ESC/EAS guidelines, and use of lipid-lowering therapies (LLT).Results13,834 patients were included: 17.15%, 13.72%, 16.82% and 49.76% were low (L), moderate (M), high (H) and very high-risk (VH) patients, respectively. The percentage of on-target patients was progressively lower towards the worst categories (78.79% in L, 58.38% in M, 33.3% in H and 21.37% in VH). Among LLT treated patients, 28.48% were on-target in VH category, 47.60% in H, 69.12% in M and 68.47% in L. We also analyzed the impact of monotherapies and combination therapies on target achievement.ConclusionsWe found relevant gaps in LDL-C management in the population of inpatients, especially in the VH category. Future efforts should be aimed at reducing cardiovascular risk in these subjects.