European Society Research Articles

Advances in Treatment for Oestrogen Receptor-Positive Breast Cancer

THIS YEAR the European Society for Medical Oncology (ESMO) Congress was hosted in Barcelona, Spain from 13th–17th September. Among the many impactful sessions, a symposium titled ‘Incorporating Novel Treatment Insights for Estrogen Receptor-Positive (ER+) Early Breast Cancer Patients’ garnered particular attention. Featuring presentations by Stephen Johnston, Royal Marsden, London, UK; Nadia Harbeck, Ludwig Maximilian University of Munich, Germany; and Etienne Brain, Institut Curie in Paris & Saint-Cloud, France, the session provided a comprehensive overview of current advances in ER+ early breast cancer treatment. The speakers explored adjuvant endocrine therapies, prognostic and predictive factors for clinical decision-making, and the unique challenges of optimising treatment for older patients, underscoring the evolving landscape of personalised care in ER+ early breast cancer.

An evaluation of the first ten years of Newborn Screening for cystic fibrosis in Ireland

Abstract Ireland has the world’s highest incidence of cystic fibrosis (CF). Newborn screening for CF (NBSCF) improves outcomes but identifies carriers and may yield false positive/inconclusive results. This study aimed to evaluate the performance of the first 10 years of the Irish NBSCF programme. Data collected by the programme between 01st July 2011 and 30th June 2021 were analysed, including cases of CF, CF carriers and Cystic Fibrosis Screen Positive Inconclusive Diagnosis (CFSPID). Microsoft Excel was used to calculate sensitivity, specificity and positive predictive value (PPV). Results were compared to European Cystic Fibrosis Society (ECFS) standards. Overall 650,809 neonates were screened, with 290 cases of CF, 533 CF carriers and 21 CFSPIDs reported. NBSCF identified 284 (98%) of the children with CF, sensitivity was 97.93% (95% CI 96.29-99.57), specificity was 99.91% (95% CI 99.91-99.92%), PPV was 0.34 (95% CI 0.31-0.37). The observed incidence of CF was 1 in 2,203, still Europe’s highest. Of the six undetected cases, most were of Asian ethnicity, suggesting panel limitations for diverse ethnicities.The Irish NBSCF programme exceeded ECFS standards. Most false negatives were caused by CFTR mutations undetected by the genetic panel. Increasing the size of the genetic panel increases detection of CFSPID and carriers and is not currently recommended. Ongoing validity monitoring is vital as the Irish population diversifies. Key messages • The Irish Newborn Screening Programme for Cystic Fibrosis is effective. • Ongoing validity monitoring is vital as the Irish population diversifies.

Cross-country price comparison of institutional long-term care: In search of suitable data

Abstract Background In European ageing societies, the national expenditure on institutional long-term care (LTC) has been growing for decades, currently exceeding 1% of the GDP in many countries. At the same time, however, comparative analyses of (day) prices in the nursing and residential care facilities (NRCFs) are still lacking. The data reported by international databases vary substantially in the services they cover which makes cross-country comparisons very difficult. Methods We combine publicly available data from Eurostat (System of Health Accounts), OECD and national sources on the number of recipients of LTC in NRCFs, the number of beds in NRCFs and the expenditure on LTC in NRCFs in over 20 European countries. Our aim is to compute internationally comparable daily prices of LTC in NRCFs using gross-costing approach. We first validate the data by cross-checking and documenting which health care functions and providers are reported by each country. Second, based on that we identify countries with comparable data and, third, perform a cross-country comparison of the daily spending on LTC in NRCFs. Results The reported data vary substantially with respect to their coverage. For instance, while some countries include NRCFs for all disabled people at all ages, others focus only on the NRCFs for the elderly. The ways the beds and the recipients are counted also show substantial variation. Moreover, we found inconsistencies in the reported numbers not only between but also within countries. Conclusions The considerable cross-country diversity in the LTC provision within the NRCFs poses inevitable challenges to international standardised reporting. Our analysis shows, however, that at least some of the challenges can be overcome by, e.g. improving the consistency of the reported numbers at the country level. Key messages • A consistent definition application markedly improves the comparability of data on LTC in NRCFs. • Given the rising demand for and economic importance of the LTC sector standardised data on NRCF services are greatly needed.

Improving the microbiological diagnosis of fracture-related infection and prosthetic joint infection through culturing sonication fluid in Bactec blood culture bottles.

Sonication of surgically removed implants appears to optimize the microbiological diagnosis in orthopedic implant-associated infections (OIAI). However, reports of infection with negative cultures can still reach high rates. A study evaluating the inoculation of sonication fluid into blood culture bottles (SFBCB) in patients with fracture-related infection (FRI) and prosthetic joint infection (PJI) is necessary. This study compared the accuracy SFBCB over the conventional sonication fluid cultures (CSFC) and tissue culture (TC). Consecutive patients who underwent implant removal surgeries due to any reason had their implants sonicated according to standardized method. Definitions of PJI and FRI were based upon criteria by European Bone and Joint Infection Society (EBJIS) and Metsemakers, respectively. Between three to five intraoperative tissue samples were processed. The implant`s sonication fluid was seeded onto sheep blood agar, chocolate agar, thioglycolate broth and on tryptic soy broth for CSFC, while was also inoculated into blood culture bottles and incubated in the automated system during 5 days for SFBCB. Overall, 74 patients were analyzed, of which 57 with OIAI (48 FRI and 09 PJI) and 17 aseptic failures (03 arthroplasties and 14 osteosynthesis). Interestingly, SFBCB demonstrated significantly higher sensitivity compared to CSFC (96.5% [95% CI, 88-100] vs. 78.9% [95% CI, 66-89], p = 0.004), and to TC (96.5% [95% CI, 88-100], vs. 57.9% [95% CI, 44-71], p < 0.001), whereas there were no significant differences in specificity between the three methods. In comparison to CSFC and TC, SFBCB improved sensitivity for diagnosing OIAI without compromising specificity.

β-Blockers and Asthma: Surprising findings from the FAERS database

Introductionβ-Blockers are essential for cardiovascular disease management but can induce respiratory issues, particularly with non-selective β-blockers. Their safety in asthmatic patients is debated. ObjectiveThis study investigates the link between different classes of β-blockers and the risk of asthma and asthma-like adverse events (AEs) using data from the Food and Drug Administration's Adverse Event Reporting System (FAERS). Methodsβ-Blockers were first reviewed according to European Society of Cardiology classification and then using the Vashistha and Kumar classification. The risk associated with different β-blocker classes was evaluated through disproportionality analysis using the reporting odds ratio (ROR). ResultsAmong 251,145 AEs reported for β-blockers, 4104 were asthma-related. Selective β1-blockers had a higher asthma risk signal (ROR: 1.15) compared to non-selective β-blockers (ROR: 0.90). α- and β-Blockers showed the lowest risk (ROR: 0.51). The Vashistha and Kumar classification detailed risk profiles for various β-blockers, highlighting differences even within the same class. Dual α- and β-blockers, hydrophilic, and lipophilic β-blockers posed lower asthma risks, while selective β1-blockers had higher risks regardless of intrinsic sympathomimetic activity. ConclusionAlthough the signals detected by disproportionality analysis are only candidate risks, the risk stratification resulting from our analysis highlights the need for cautious β-blocker selection in asthmatic patients or those predisposed to asthma. Furthermore, despite the limitations associated with the FAERS data, the study reveals significant variability in risk among different β-blocker classes, crucial for clinical decisions and patient management. Drugs like esmolol, metoprolol, nebivolol, and nadolol may be safer for asthmatic patients, whereas betaxolol, bisoprolol, timolol, and propranolol should be avoided.

Improving the functional detection of sarcopenic obesity: prevalence and handgrip scoring in the OBESAR cohort.

The study objectives were: 1) to detect early signs of low muscle function and assess sarcopenic obesity (SO) prevalence in patients with obesity; and 2) to introduce a new online diagnostic tool for scoring handgrip strength (HGS), adjusted for age and sex. Patients from the OBESAR cohort (184 men and 499 women) were tested for body composition and functional testing (chair stand test or HGS based on the cutoffs from the European Society for Clinical Nutrition and Metabolism [ESPEN]/European Association for the Study of Obesity [EASO] or adjusted HGS [adHGS] based on reference values), and SO prevalence was calculated accordingly. Among the 683 patients (mean [SD], age 42.6 [12.8]years; BMI 44.4 [6.3] kg/m2), HGS averaged 25.6 (6.8) kg for women and 43.2 (10.4) kg for men. A total of 25.2% of patients had adHGS lower than the 10th percentile, but this was true for only 5.6% using ESPEN/EASO cutoffs of HGS. SO prevalence rates were different according to functional tests: 5.4%, 24.5%, and 3.2% for HGS, adHGS, and the chair stand test, respectively. Using adHGS through a scoring process considering age and sex may help to detect early signs of SO in a primary care setting in order to better prevent SO through a personalized approach in adults with obesity. A free online application, "GRip And Sarcopenia Prediction" (GRASP), is proposed to diagnose probable SO.

Clinical validated risk prediction model for development of heart failure after contemporary breast cancer treatment

Abstract Background Patients receiving breast cancer (BC) treatment are at risk for heart failure and cardiomyopathy (HF/CM). European Society of Cardiology (ESC) cardio-oncology guidelines recommend baseline cardiovascular (CV) assessment, however, there is limited data about cardiotoxicity risk specific to patients with BC. Our aim was to develop and validate model for prediction of HF/CM in women receiving contemporary treatment for invasive early-stage BC. Methods We assembled a cohort women diagnosed with Stage I-III BC from 2008-2020 and followed through 2021 in a large health care plan. Women age &amp;gt;80, with history of HF/CM, and women who received both anthracyclines and trastuzumab were excluded, leaving N=26,044 for analysis. Study cohort was randomly split into derivation (60%) and validation (40%) datasets. Elastic-net penalized Cox proportional hazard model was created using the derivation dataset to select risk factors and to calculate the panelized coefficient which defined the HF/CM risk score. Risk score system was assessed by Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC). Event rates of &amp;lt;5% constituted low risk; 5-14% moderate; and &amp;gt;15% high risk category. Incident HF/CM events were examined using Kaplan-Meier approach in derivation and validation datasets. Results HF/CM risk score had high discrimination ability and sufficiently good model of fit regarding HF/CM events (P value=0.163 and 0.667 from Hosmer–Lemeshow test;AUC 0.751 and 0.764, in derivation and validation sets, respectively). There were 10% of women in the high risk; 30% in moderate; and 60% in low-risk group. Variables associated with the higher HF/CM risk score included age, receipt of anthracycline-based chemotherapy or anti-HER2 therapy, presence of hypertension, diabetes, or history of other CV conditions at baseline. The score pattern showed major effect of age, with anthracycline and anti-HER2 therapy increasing the risk across all age groups (Figure 1). Kaplan-Meier analysis of incident HF/CM over 14 years after BC diagnosis showed significantly lower number of HF/CM events in low risk compared to moderate and high-risk score groups (p&amp;lt;0.0001, Figure 2). Conclusion Our robust risk prediction model for HF/CM among women with early-stage BC provides a new tool to identify women at higher CV risk and inform cardiac function monitoring during and after BC treatment. Our findings may guide further validation studies and build evidence for the cardiotoxicity risk stratification in patients with BC.Risk Score for HF/CM by Age/ChemoTxK-M curves of freedom from HF/CM

Correlative study to assess the predictive power of the ICOS HF calculator in the prediction of development of HER-2 antagonist induced cardiac dysfunction in a single center in Saudi Arabia in 2023

Abstract Background Over the past 3 decades, there has been a significant increase in cancer survivors supported by the major advances in cancer therapies. However, most of those therapies are cardio-toxic. In 2022, the European Society of cardiology had published, for the first time, a clinical guideline that describes how to manage this cohort of patients, and endorsed the utilization of a risk calculator to predictor likelihood of development of cancer therapy cardiac dysfunction (CRTCD). We did retrospective review of all consecutive patients that have received Trstuzumab (HER-2 antagonist) in the year 2023 in a single tertiary cardiac center. We assessed their demographics and co-morbidities, incidence of CRTCD, evaluated their ICOS-HF score and looked for any CRTCD in this cohort to assess whether the calculated stratification correlated with development of CRTCD. The objective is to assess the utilization of this tool in our patient population. Methods 369 unique individuals were identified from the hospital databas that had received HER-2 antagonists. Basic patient demographics were extracted from the information system along with their clinical, laboratory, and echocardiographic data. Their risk profiles were stratified using the ICOS-HF calculator. Follow up echocardiogrphic studies were reviewed to assess the incidence of CRTCD in patients receiving HER-2 antagonists and the correlation between the risk strata using the ICOS-HF and actual development of CRTCD. Results The average age was 53+/- 11 years. 96.8% were females. At baseline, 20% were diabetic, 26.8% were hypertensive, 10.8% were dyslipidemic, 1.9% had prior cardiomyopathy or heart failure, 1.3% had IHD, 1.1% were smoker, 33.3% were obese, and 3.8% had CKD. Overall, in the year 2023, the incidence of HER-2 induced cardiac dysfunction was 10.6%. At baseline, using the ICOS-HF calculator, 57.9% were stratified as low risk, 21% as moderate risk 14.6% as high risk, and 6.5% as very high risk. Approximately 5% of the patients with low to moderate risk developed CRTCD, which rose to 18.5% in the high risk, and significantly rose to 58% in the very high risk population. Conclusion The risk stratification using the ICOS-HF calculator in consecutive patients receiving Trastuzumab correlated directly with the likelihood of developing CRTCD. 58% of all of the patients in the very high risk category developed CRTCD. This retrospective analysis validates the use of this tool in our patient population and will aid in the identification of patients that would require to have a more aggressive preemptive management, especially in the high and very high risk population using a multidisciplinary cardio-oncology team to optimize their surveillance and reduce their likelihood of cardiac dysfunction.

Development of a systematic referral model to primary care health interventions for patients with atrial fibrillation. a delphi study

Abstract Background The European Society of Cardiology (ESC) guidelines for the management of atrial fibrillation (AF) recommend integrated care in AF, combining medical treatment with lifestyle modifications and psychosocial management in a multi-disciplinary set-up. Research show that patients with AF can benefit from lifestyle interventions and psychosocial management, like patient education. According to World Health Organization recommendations, these health interventions are moving from hospitals to primary healthcare settings. Therefore, patients with AF should be systematically referred to these interventions. Yet, an evidence-based referral model that can support this transition is lacking. Purpose The purpose is to develop a systematic referral model for primary care health interventions for patients with AF. Methods We used the Delphi-technique with three rounds of questionnaires (figure 1). International and national clinical experts in AF across disciplines and health sectors were invited to participate. In the first round, the expert panel evaluated items that could be part of a referral model on relevance, improvability and self-reporting. In the second round, the expert panel evaluated each item as either an inclusion or exclusion criteria, important knowledge to have, or not relevant. In the third round, the expert panel evaluated the items according to data source and outcome status. A final model was drawn based on items reaching consensus. The study was reported according to the guidance on conducting and reporting Delphi studies (CREDES). Results In total, 69 of 139 invited experts accepted to participate (50%). These were mostly academics or clinicians (90%), stemming from primary sector (16%), secondary sector (35%) and research (32%). Most were medical doctors (36%) and nurses (35%). However physiotherapist, psychologists, dieticians, and other disciplines along with six patients with AF were also represented. The expert panel (60% females) had a mean age of 50 years, and 65% were from Denmark. For the final referral model (figure 2), AF symptom burden and impaired health-related quality of life, anxiety and poor medicine compliance combined with a risk factor profile were the main inclusion criteria. Furthermore, it was important to know about the patients’ mental well-being, self-management abilities and comorbidities. Conclusion Consensus was reached for a generic referral model, which can be further adjusted in the appropriate clinical context. The model includes inclusion criteria which closely correlate with guidelines for AF management focusing on reducing the patients’ symptom and risk factor burden. The referral model is expected to increase the number of patients with AF referred to primary care health interventions, which could lead to better quality of life, fewer hospital admissions and lowered health care costs in AF.

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

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

External validation of a stepwise 0/1/3h algorithm to triage patients with suspected myocardial infarction

Abstract Background In patients with suspected myocardial infarction (MI), application of 0/1h-algorithms is recommended by guidelines of the European Society of Cardiology. Depending on assay-specific changes of high-sensitivity troponin (hs-Tn), these algorithms allow for rule-in or rule-out of MI at presentation or after 1 hour (h). Yet, a relevant proportion of patients remain in the observe group at 1h in need for further diagnostic. Recently, specific cutoffs at 3h were suggested for hs-TnT, enabling an additional 3h triage option in conjunction with the 0/1h algorithm to further reduce the proportion of patients in the observe zone. Objective We aimed to externally validate the diagnostic performance of the 0/1/3h algorithm in patients with suspected MI. Methods We consecutively enrolled patients with symptoms suggestive of MI in the emergency department of a tertiary hospital in Germany. Patients with STEMI were excluded. Concentrations of hs-TnT were measured at presentation, after 1h and 3h. Final diagnoses were adjudicated by two cardiologists according to the 4th Universal Definition of MI. Applying the 0/1/3h algorithm, patients were triaged into rule-in, rule-out- and observe-group. We assessed the diagnostic performance parameters in the overall sample as well as for predefined subgroups including sex, age ≥65 vs. &amp;lt;65 years, glomerular filtration rate (GFR) ≥60ml/min/m² vs. &amp;lt;60ml/min/m², and symptom onset time &amp;lt;1h vs. 1-3h vs. &amp;gt;3h). Results In 2,514 patients (median age 64 years, 36.4% female), prevalence of NSTEMI was 14.4%. Application of the 0/1/3h algorithm ruled-out 1511 (60.1%) and ruled-in 587 (23.3%) patients. Only 416 (16.6%) remained in the observe group at 3h. Safety of rule-out was high with a sensitivity of 98.6% (95%CI 96.8%, 99.4%) and a corresponding negative predictive value of 99.7% (95%CI 99.2%, 99.9%). Rule-in performance was acceptable with a specificity of 89.3% (95%CI 87.9%, 90.5%) and positive predictive value (PPV) of 60.8% (95%CI 56.8, 64.7, Figure 1). Regarding subgroup analyses, sensitivity and NPV were marginally but statistically lower in patients with normal as compared with impaired renal function (p both &amp;lt;0.001). Further, specificity was substantially lower in older patients (84.8% vs. 93.3%, p&amp;lt;0.001), patients with GFR&amp;lt;60ml/min/m² (78.3% vs. 93.0%, p&amp;lt;0.001) as well as in male patients (88.1% vs. 91.2%, p=0.028) (Figure 2). A relevantly larger proportion of patients remained in the observe group after 3h in patients with impaired renal function (32.3% vs. 10.9%), as well as in patients aged ≥ 65 years (26.8% vs. 6.8%). Conclusion Application of the 0/1/3h algorithm in patients with suspected MI resulted in good diagnostic performance with excellent rule-out safety and moderate rule-in capacity. In patients with impaired renal function as well as elderly patients, specificity was significantly lower while observing a larger proportion of patients remaining in the observe zone at three hours.Figure 1:Diagnostic flowFigure 2:Forest Plots

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) &amp;lt;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

Optimizing patient selection for cardiac resynchronization therapy in a multicenter study of Japanese patients: assessment of the MADIT-ICD benefit group

Abstract Background The MADIT-ICD benefit group, derived from ventricular tachycardia (VT)/ventricular fibrillation (VF) scores and non-arrhythmic mortality scores (Table 1), facilitates the appropriate selection of candidates for implantable cardioverter-defibrillator (ICD) therapy. While the 2021 European Society of Cardiology Guidelines have discussed the advantages and considerations of adding a defibrillator in patients undergoing cardiac resynchronization therapy (CRT), the optimal selection of CRT with or without a defibrillator remains unclear, particularly in Asian populations. This is especially relevant for primary prevention using ICD, which is characterized by fewer cases of ischemic etiology compared to Western countries. Purpose This study aimed to evaluate the utility of the MADIT-ICD benefit group in Japanese CRT patients and identify key indicators for determining the necessity of CRT with or without a defibrillator. Methods We conducted a retrospective, multicenter evaluation of 505 consecutive Japanese CRT patients enrolled between 2012 and 2020. Among these patients, 76% were male, with a mean age of 65 years and a mean body mass index of 22.5 kg/m2. Ischemic etiology was present in 25% of patients, with 20% undergoing secondary prevention. The study assessed the cumulative incidences of VT/VF and non-arrhythmic mortality based on the MADIT-ICD benefit group (lowest, intermediate, and highest). Predictors for each outcome were explored, and the MADIT-ICD benefit group was validated in the Japanese cohort. Results Of the 400 included patients, 60 (15%) were categorized into the lowest MADIT-ICD benefit group, 279 (70%) into the intermediate group, and 61 (15%) into the highest group. Over a median follow-up period of 34 months, VT/VF occurred in 4 (13%), 68 (24%), and 14 (23%) patients in the lowest, intermediate, and highest benefit groups, respectively (Gray’s test, P = 0.027, Figure 1A). Non-arrhythmic death occurred in 15 (25%), 91 (33%), and 9 (15%) patients in the lowest, intermediate, and highest benefit groups, respectively (Log-rank test, P = 0.025, Figure 1B). Multivariable analysis identified MADIT-ICD VT/VF score (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.12-1.35; P &amp;lt; 0.001) and left bundle branch block (LBBB) (HR 0.48; 95% CI 0.27-0.86; P = 0.014) as significant predictors for VT/VF, while MADIT-ICD non-arrhythmic mortality score (HR 1.16; 95% CI 1.07-1.27; P &amp;lt; 0.001), serum creatinine (Cr) (HR 1.28; 95% CI 1.13-1.45; P &amp;lt; 0.001), and mineral corticoid receptor antagonist (MRA) use (HR 1.84; 95% CI 1.21-2.79; P = 0.004) were significant predictors for non-arrhythmic death (Table 2). Conclusion The MADIT-ICD benefit group, in conjunction with left bundle branch block and renal function, may serve as valuable predictors for determining the necessity of cardioverter-defibrillator therapy in Japanese CRT patients.Table 1 and Figure 1

Impact of new definition on the prognosis of patients with pulmonary hypertension compared to classic definition

Abstract Background The recent European Society of Cardiology (ESC)/European Respiratory Society (ERS) 2022 pulmonary hypertension (PH) guidelines have updated the definition of PH from a mean pulmonary arterial pressure (mPAP) ≥ 25mmHg to &amp;gt; 20mmHg, and the pulmonary vascular resistance (PVR) threshold for pre-capillary PH (Pre-PH) from &amp;gt; 3 wood units (WU) to &amp;gt; 2 WU. Little is known regarding the implication of this new criteria in all PH subgroups in Asia. Purpose In this study, we aim to evaluate the impact of the new PH definition on the prevalence and prognosis of PH subgroups in as Asian cohort. Methods A retrospective analysis of a single-center RHC registry (April 2016 - July 2023) was conducted. 314 patients (median age 62.5, 50.3% men) were included. Patients were categorized into PH subgroups as defined by both the classic and new criteria. The primary outcome included cardiovascular mortality or heart failure hospitalizations, assessed over a maximum follow-up period of 5 years. Clinical outcomes of different PH subgroups using the classic and new definitions were compared using Kaplan-Meier methods, log-rank tests, and Cox proportional hazards models. Continuous parameters were analyzed using restrictive cubic splines within Cox models. Results Based on the new cutoffs (mPAP &amp;gt; 20mmHg, PVR &amp;gt; 2 WU), 76 patents (24.2%) were reclassified. PH increased to 233 (+ 41, +13.1%), Pre-PH increased to 92 (+ 30, +9.6%), Ipc-PH decreased to 27 (- 21, -6.7%), and Cpc-PH increased to 108 (+33, +10.5%). Over a median follow-up of 238.5 days, 65 primary outcomes occurred. Under the new PH definition, 5-year survival rates for Pre-PH, Ipc-PH, and Cpc-PH are 73.2%, 57.5%, and 47.0%, improved from 67.0%, 53.3%, and 44.3% in the classic definition. In the Cox regression analysis, using the Non-PH as a reference, the risk of primary outcome for PH subgroups was lower in the new definition compared to the classic definition (Table 1). Using the classic mPAP cut-off [&amp;lt;25 vs. ≥25 mmHg], patients with PH had a significantly higher risk for primary outcome (HR 2.25, 95% CI 1.26-4.00, p=0.006) compared with patients without PH. However, using the new mPAP cut-off [&amp;lt;20 vs. ≥20 mmHg], it didn’t show significant difference between two groups (HR 1.62, 95% CI 0.86-3.04, p=0.132). Spline analyses suggested a linear relation between the risk of primary outcome and mPAP considering mPAP between 20 and 45mmHg, and a plateau of events for mPAP values over 45mmHg. In patients with PVR &amp;gt; 2 WU, we observed a linear relation between PVR and events for values and a plateau of events for PVR values over 7.5 WU (Figure 1). Conclusion The new definition increased the diagnosis of PH, particularly in Pre-PH and Cpc-PH. This definition faciliates earlier diagnosis, encompassing milder disease states, and demonstrated better prognosis in PH subgroups. However, it dose not identify additional patients at increased risk of primary outcomes.Table 1Figure 1

Circulating Amyloid beta 1-40 is independently associated with statin treatment and LDL cholesterol reduction: a prospective cohort study

Abstract Background Accumulating evidence suggests that circulating amyloid beta 1-40 (Aβ40), a pro-inflammatory and pro-atherogenic peptide, is associated with atherosclerotic cardiovascular disease (ASCVD), providing incremental prognostic value and risk stratification refinement in primary and secondary prevention settings. Existing evidence supports conflicting off-target effects of statins on plasma Aβ40. We aim to explore the impact of cardiovascular risk reduction through statin therapy on Aβ40 plasma levels in subjects with dyslipidemia and with/without ASCVD. Methods In this prospective study, patients with dyslipidemia who visited for the first time our lipid clinic for risk stratification and treatment plan assessment (n=146) were consecutively recruited. Αβ40 was measured in plasma samples by enzyme-linked immunosorbent assay at baseline and after a mean follow-up of 5.2 and 15 months. Patients in whom statin treatment was initiated or intensified in terms of dose or regimen (n= 68) were compared against patients not treated with statins or with unchanged statin intensity (n = 78). Statin intensity treatment was defined based on the European Society of Cardiology (ESC) guidelines. Results Increased Aβ40 plasma levels at baseline were associated with ASCVD presence, decreased glomerular filtration rate (GFR), and history of heart failure (p&amp;lt;0.05 for all). An increase in Aβ40 circulating levels between baseline and follow-up 1 was observed in patients in whom statin treatment was initiated or intensified (p=0.041). However, in patients not treated with statins or treated with unchanged statin intensity, an increase in Aβ40 circulating levels was observed between follow-up 1 and follow-up 2 (p=0.05, Figure 1A). These changes in Aβ40 were significantly different between the two groups during the short follow-up period (β=0.226, p for interaction =0.025) independently from age and changes in GFR, systolic blood pressure, and LDL-C. Additionally, patients who achieved a reduction in low-density lipoprotein cholesterol (LDL-C) ≥ 50% in follow-up 2 have unchanged Aβ40 levels during the long follow-up period, while an increase in Aβ40 was observed in the rest population (p=0.012, Figure 1B). These changes were significantly different between the two LDL-C groups independently of statin treatment and changes in high sensitive C-reactive protein (hs-CRP) (β= -0.231, p for interaction=0.035). Conclusion In a dyslipidemic population, statin initiation or intensification and LDL-C decrease showed a short-term increase and a long-term return to initial levels, respectively, in circulating Aβ40 levels. From a mechanistic point of view, our findings suggest that statins have an impact on Aβ40, possibly through an LDL-C-dependent and a non-LDL-C-dependent pathway. Further studies are needed to evaluate the utility of circulating Aβ40 as a novel biomarker in ASCVD risk reduction assessment.

Low clinical utility of global longitudinal strain in a real-world breast cancer population

Abstract Background The 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines recommend the use of global longitudinal strain (GLS) to detect mild asymptomatic cancer therapy related cardiac dysfunction (ma-CTRCD). However, it remains unknown how to best manage these patients in order to prevent clinically significant CTRCD. Purpose To assess the course and outcomes of breast cancer patients meeting criteria for ma-CTRCD. Methods Echocardiograms and medical records were assessed for breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring, including routine GLS. CTRCD was defined as an absolute decline in LVEF of &amp;gt;10% to &amp;lt;50%. ma-CTRCD was defined as a relative decline in average GLS of &amp;gt;15%, in the absence of significant LVEF decline. Normal was defined as no significant change in LVEF or GLS during cancer therapy. Clinical and echocardiographic course post ma-CTRCD detection was assessed. Baseline risk factors were compared between the three groups. Results 878 echocardiograms from 258 patients were analysed. GLS analysis was available in 76% of echocardiograms. CTRCD occurred in 23 (9%) and ma-CTRCD in 63 (24%). Only eight ma-CTRCD patients had management altered (cancer therapy withheld/ceased in three and heart failure medication commenced in six). Only two ma-CTRCD patients subsequently developed CTRCD, and GLS improved in 74%. Compared to the normal group (172, 67%), at baseline the ma-CTRCD group had higher average GLS (-21.8 vs -19.4, p&amp;lt;0.0001) and less borderline/abnormal average GLS (4% vs 36%, p&amp;lt;0.004). Conclusion Isolated declines in GLS are common and may have low clinical utility in preventing CTRCD. The findings support ESC guideline recommendations that cancer therapy should not be withheld in these patients. Those with higher baseline GLS may be more prone to clinically insignificant declines in GLS during cancer therapy.

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 &amp;lt;-18, (43% vs 19%, p=0.04) and combination anthracycline plus trastuzumab, (45% vs 22%, p=0.0392). Left atrial volume index &amp;gt;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

Reinterpretation of genetic testing for Cardiomyopathies: Less is more

Abstract Background In the last years, the concept of reinterpretation of genetic testing has been considered as part of the diagnostic workflow. However, this process requires time, expert curators and new pieces of evidence to evaluate, as functional studies, segregation and allele frequency data. Last year, the European Society of Cardiology (ESC) published new guidelines for the management of cardiomyopathies. This document includes a precise list of genes associated with the different types of Cardiomyopathies and their level of contribution, according to ClinGen evaluation: definitive/strong, moderate, limited, and refuted/disputed. This document poses a real support in the reinterpretation of tests that report variants in genes not clearly correlated with these phenotypes. Purpose To evaluate the impact of the new ESC indications regarding genetic testing, we reconsidered all genetic results performed in our Clinic in patients with confirmed or suspicious Cardiomyopathy. Methods From 2017 to 2023 we analyzed 296 probands eligible for Cardiomyopathy genetic testing, in particular: 105 patients were tested for Arrhythmogenic Cardiomyopathy (ACM), 113 for Hypertrophic Cardiomyopathy (HCM) and 78 for Dilated Cardiomyopathy (DCM), using a custom sequencing panel including 44 genes (11 genes for ACM, 34 for DCM and 29 for HCM). Results Comparison analysis with the genes reported from the ESC guidelines, considering only the definitive, moderate, and strong genes, showed that 24 genes are not more associated with the phenotype and then not clinically actionable. In this scenario, we reconsidered 12 variants (8%), previously classified as VUS, changing the referral status of 8 patients, from uncertain to negative. Conclusions These results highlight the importance of variant reinterpretation as a fundamental step of genetic testing, posing the importance of the selection of the genes to analyze, in order to improve the management of the patients.

Efficacy and safety of catheter ablation for paroxysmal atrial fibrillation as first-line therapy vs. after drug failure -analysis from Japan Nationwide Ablation (J-AB) Registry-

Abstract Background Catheter ablation is an effective rhythm control therapy for atrial fibrillation (AF). Recent advancements in technology have improved the efficacy and safety of this procedure. Current European Society of Cardiology and Japanese Circulation Society guidelines recommend that catheter ablation (CA) for patients with paroxysmal AF (PAF) after failure of drug therapy is classified as Class I, and CA as first-line therapy is categorized as Class IIa. However, there are limited clinical studies directly comparing these groups. Objective This study aimed to compare the efficacy and safety of CA as first-line therapy vs. those after failed drug therapy using data from the Japan Nationwide Ablation (J-AB) Registry led by the Japanese Heart Rhythm Society. Methods Detailed data of patients who underwent catheter ablation for PAF extracted from the J-AB registry were analyzed. Patients were divided into two groups: those who underwent CA as first-line therapy (First-line group) or those who underwent CA after failed drug therapy (Drug failure group). Patients’ characteristics, efficacy and safety of CA were compared between the two groups. Efficacy was assessed by evaluating the recurrence rate of any atrial arrhythmia within one year after the 90-day blanking period, and major safety outcomes were set as severe bleeding complication, stroke, and gastrointestinal disorders during the perioperative period. Result This analysis included 5,011 cases with a median age of 69 years (range 61-75) and 35% females. Comparing patient characteristics between the first-line therapy group (n = 3,447) and the drug failure group (n = 1,564), there are no statistically significant differences between the two groups except in left atrium diameter in echocardiogram (LAD) (38 [34-42] mm vs. 38 [34-43] mm, P &amp;lt;0.001), serum creatinine levels (0.8 [0.7-1.0] mg/dl vs. 0.9 [0.7-1.0] mg/dl, P &amp;lt;0.001), and beta-blocker usage (38.2% vs. 46.7%, P &amp;lt;0.01). A total of 501 recurrence events were observed in this analysis during a median follow-up of 365 [254-390] days. Recurrence rates did not statistically differ between the two groups (log-rank P=0.49). After adjusting for contributing factors with age, gender, body mass index, LAD, and left ventricular ejection fraction in echocardiogram using a multivariate Cox proportional hazards model, efficacy outcomes showed no significant difference between the two groups (adjusted hazard ratio; 1.06 95% confidence interval; 0.88-1.28, P = 0.55). Besides, the two groups had no significant difference in major safety outcomes. Conclusions Catheter ablation as the first-line therapy for paroxysmal atrial fibrillation showed a similar recurrence rate of atrial arrhythmias and adverse events compared to those who underwent catheter ablation after drug failure.

Determinants of changes in peak oxygen consumption in patients with new onset heart failure

Abstract Background Patients with heart failure (HF) with reduced ejection fraction (HFrEF) have a high risk of mortality. Cardio-Pulmonary Exercise Test (CPET) assesses peak oxygen consumption (pVO2) which is considered a key predictor of mortality and morbidity in patients with HFrEF. Factors responsible for the changes in pVO2 could consequently be of interest, as optimizing these factors may improve prognosis and overall quality of life in patients with HFrEF. Purpose To investigate factors contributing to changes in pVO2 within a contemporary cohort of new-onset patients with HFrEF. Methods From December 2022 to September 2023, patients with new-onset HFrEF (European Society of Cardiology (ESC) criteria) were included from a HF outpatient clinic, who after referral to the clinic underwent 12 weeks of HF management according to ESC guidelines. This included physical training and optimization of pharmacological management of HFrEF. Baseline characteristics, CPET, medication and echocardiography were collected at referral and after 12 weeks. Changes in pVO2 were investigated according to baseline characteristics, changes in medication, and changes in echocardiographic parameters in both uni- and multivariable linear regression models. Significant independent variables were identified using stepwise selection (p&amp;lt;0.1), adjusted for age and sex. A p-value of 0.05 was considered significant. Results We included 48 patients with new-onset HFrEF with a median age of 73 (interquartile range (IQR): 60-77) years, 10 (20.8%) women, a baseline median left ventricular ejection fraction (LVEF) of 30% (IQR: 25-35), and a baseline median pVO2 of 17.3 ml/min/kg (IQR: 14.1-21.9). After 12 weeks, pVO2 improved with a mean of +2.18 ml/min/kg (95% confidence interval (CI) 1.25 to 3.10, p&amp;lt;0.01) and LVEF improved with a mean of +11.7% (95% CI 7.9 to 15.6, p&amp;lt;0.01). In univariable analyses increasing age were negatively associated with pVO2 changes (p=0.04) and increasing minute ventilation (MV) and initiation of sodium-glucose cotransporter (SGLT2) inhibitors were all positively associated with pVO2 changes (p&amp;lt;0.01 and p=0.03, respectively). Other clinical variables included in the analysis were not significantly associated with a change in pVO2. In the multivariable analysis, body mass index emerged as an independent variable negatively associated with pVO2 changes, and MV and initiation of SGLT2 inhibitors remained significantly positively associated with pVO2 changes. Conclusion Optimal pharmacological management and physical training in patients with new-onset HFrEF, induce a significant recovery of cardiorespiratory performance and ejection fraction. Furthermore, our results suggest that the initiation of SGLT2 inhibitors in patients with new-onset HFrEF appears to improve their pVO2 already after 12 weeks of optimal HF management.Table 1:BaselineTable 2:Associations