Severe Valvular Disease Research Articles

Tricuspid regurgitation in the context of severe concomitant left-sided valvular heart disease: patients characteristics and long-term clinical and interventional outcomes

Abstract Background The clinical features, therapeutical management and outcome of patients with significant tricuspid regurgitation (TR) in the context of multiple valvular disease (VD) are poorly defined. Purpose To assess the characteristics, management and long-term prognosis of a large cohort of patients with multiple VD, focusing on the context of significant TR and concomitant severe mitral or aortic disease. Methods Clinical and echocardiographic data were collected in 1183 patients with ≥moderate TR diagnosed at our centers from January 2012 to June 2020: after propensity score matching for age to create matched cohort with < 10% of absolute difference, 975 patients were included in this study and divided in 4 groups as shown in Figure 1. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization+any valvular intervention. Results Patients with isolated TR (356, 37%) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). TR+ severe MR patients (466, 48%) showed higher rates of concomitant coronary artery disease, NYHA class III/IV symptoms and larger left atrial volumes. The group of TR+ severe AS (131 patients, 13%) was characterized by older age, more comorbidities and lower LVEF. Patients with TR and severe AR (22, 2%) were younger, with larger LV dimensions and higher pulmonary pressures. Overall, in 37(4%) patients tricuspid intervention was performed: no differences were found between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment (p=0.444 and p= 0.624, respectively), while left-valve only surgical treatment was more common among patients with TR and severe MR and left-valve transcatheter treatment among patients with TR and severe AS (both p<0.001). After a median follow-up of 2.8 years, the primary endpoint occured in 374 (38%) of patients, and was significantly more frequent in the group of patients with TR and severe AS (p<0.001, Figure 2). In this group, after multivariate analysis, indexed stroke volume remained independenty associated with ACD (OR 0.96, CI 0.93-0.98, p =0.040). Eventually, the secondary endpoint too was more common in patients with TR and severe AS (p<0.001, Figure 2). Conclusions In the context of significant TR, concomitant severe left-sided VD is common, and each subtype presents with different clinical features and echocardiographic phenotypes; in this scenario, TR was profoundly underteated. Long-term, patients with significant TR+ severe AS have considerable worse prognosis.Figure 1Figure 2

Valvular heart disease and out-of-hospital cardiac arrest

Abstract Background The prevalence of valvular heart disease is on the rise. Severe valvular diseases are generally associated with high mortality, and aortic stenosis (AS) is associated with halved survival after out-of-hospital cardiac arrest (OHCA). Despite the severity of the prognosis of valvular heart diseases, their association with the risk of OHCA is not well-elucidated. Purpose The study aimed to examine the association between valvular heart disease and OHCA. Method We conducted a study using data from the nationwide Danish Cardiac Arrest Registry. We included adult OHCA patients with presumed cardiac origin. We compared OHCA cases with and without valvular heart disease, stratified by valvular disease type (AS, aortic regurgitation (AR), mitral stenosis (MS), and mitral regurgitation (MR) or multiple valvular diseases (more than 1 concomitant type of valvular disease)). We calculated the hazard ratios of OHCA using time-varying Cox regression models fitted with a nested case-control design. For each case, we matched up to five controls based on age, sex, year of OHCA, and two comorbidities: ischemic heart disease and congestive heart failure. Results We included 43,967 OHCA cases and 219,772 controls matched from the general population. In the total case population, the median age was 72 years, 68% were male, 26% had ischemic heart disease, 21% had congestive heart failure, and 57% had cardiovascular risk factors. We identified 1862 (4.23%) cases with AS, 336 (<1%) with AR, 31 with MS (<1%), 710 with MR (1.6%), and 605 with multiple valvular diseases (1.4%). Compared with cardiac arrest cases without valvular disease, cases with valvular disease were more likely to have ischemic heart disease (e.g., AS vs controls: 6.5% vs 1.7%, p<0.001) and congestive heart failure (e.g., MR vs controls: 3.5% vs 1%, p<0,001; AS vs controls: 8.2% vs 2.8%, p<0.001). AS, MS (HR: 1.67 [95%CI: 1.12; 2.51]), MR (HR: 1.38 [95%CI: 1.27; 1.50]) and multiple valvular diseases (HR: 1.36 [95%CI: 1.24; 1.49]) were significantly associated with higher hazard of OHCA (Figure 1); the strongest association was seen for AS (HR: 1.66 [95% CI: 1.58; 1.76]) (Figure 1). AR was not significantly associated with OHCA (HR: 1.05 [95%CI: 0.94; 1.19]). Conclusion In this Danish nationwide cardiac arrest cohort, aortic stenosis, aortic regurgitation, and mitral regurgitation were associated with increased rates of OHCA. The association was strongest in aortic stenosis patients. Focus on risk factors of OHCA in patients with valvular heart disease is warranted.Figure 1

Ventricular and supraventricular ectopic beats burden is correlated with bone mineral density and osteoporotic fracture risk in postmenopausal females

Abstract Introduction Patients (pts) with osteoporosis (OP) have an increased 10-year cardiovascular death risk. Low bone mineral density (BMD) observed in OP may be associated with arrhythmic presentation of cardiovascular diseases (CVD). Few studies assessed the relationship between OP and arrhythmia. Aim Arrhythmias assessment in pts with OP. Methods A total of 103 postmenopausal female pts (mean age 69 +/- 7), consulted by endocrinologist, were divided into 2 groups according to BMD (assessed by dual energy X-ray absorptiometry). BMD measurements, expressed as T-score (T-sc), were taken from the femoral neck (T-sc Neck), entire total hip (T-sc TH) and/or spine (T-sc L2-L4, L1-L4). Arrhythmia was evaluated using 24-hour Holter-ECG monitoring (HM). Major osteoporotic and total hip fracture risks (MOFR and THFR, respectively) were assessed by the FRAX scale. We compared 51 pts with OP (T-sc ≤ -2.5), with 52 matched controls without OP, including 44 pts with osteopenia (T-sc > -2.5). There were no significant differences between the groups regarding the history of stroke, myocardial infarction, coronary artery disease or arterial hypertension. Exclusion criteria included heart failure NYHA >II and/or LVEF <36%, acute coronary syndrome within the last 6 months, severe valvular disease, cardiac implantable electronic device. Results There was a trend towards a greater number of supraventricular and ventricular arrhythmias in the OP group compared to the controls. Arrhythmic burden was significantly correlated with BMD measures: correlations were observed between 24-hour ventricular ectopic beats (VEB) count with T-sc Neck (r=-0.20, p=0.04), with T-sc TH (r=-0.22, p=0.03). The number of supraventricular ectopic beats (SVEB) in HM was also correlated with BMD parameters: T-sc Neck (r=-0.21, p=0.03), T-sc TH (r=-0.23, p=0.02). Multivariate analysis (linear regression model) revealed that age and T-sc TH were independently related with ectopy: age (0.07; CI: 0.01 - 0.13, p=0.03) and T-sc TH (-0.58; CI: -1.07 - -0.08, p=0.02) were predictors for VEB, and SVEB were related to age (0.07; CI: 0.03 - 0.12, p<0.01) and, with borderline significance with T-sc TH (-0.34; CI: -0.699 - 0.012, p=0.058). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR (r=0.206, p=0.04) and SVEB with MOFR (r=0.21, p=0.04). Conclusions The study showed an increased arrhythmia burden as detected in HM in pts with OP. Beside the T-sc TH, age was identified as an independent factor of increased SVEB / VEB. The main significant negative correlations were observed between the number of VEB / SVEB and BMD in femur (T-sc Neck, T-sc TH). Ectopic beats count was also positively correlated with osteoporotic fracture risk: VEB with THFR and SVEB with MOFR.

Association of soluble ST2 with heart failure and other comorbidities in patients with severe coronary heart disease

Abstract Background Circulating levels of soluble suppression of tumorigenicity-2 (sST2) reflect vascular congestion, inflammation, and fibrosis. sST2 has been proposed as a useful biomarker to predict the mortality and hospitalization due to heart failure. However, there is limited evidence regarding the relationship between sST2 and heart failure, as well as other comorbidities, in severe coronary heart disease (CAD). Purpose This study aims to measure the circulating levels of soluble ST2 (sST2) in a large population of patients with severe CAD to determine its association with heart failure, cardiac function, inflammation, and other important comorbidities. Methods This subanalysis is part of the ongoing perspective observational study. Available serum samples from 520 patients undergoing elective coronary artery bypass grafting (CABG) were analysed for sST2 levels. The inclusion criteria were written informed consent and age between 18-85 years. Exclusion criteria for this analysis were severe valvular disease, severe chronic obstructive pulmonary disease, oxygen therapy, nocturnal positive airway pressure support or mechanical ventilation, and the need for catecholamines or circulatory assist devices. The circulating levels of human sST2 were measured from frozen serum (-80°C) using commercially available ELISA kits. The plasma was diluted 100 times to detect sST2 levels (assay range of 31.2 - 2,000 pg/mL). Two measurements were taken to account as means for intra-assay variabilities. Logarithmic transformation was used to convert non-normal distributed data. Student t' test and linear regression were applied to categorical or continuous variables as appropriate. Results sST2 levels (median 20.4 ng/ml, [IQR 15.5 – 28.8]) significantly predict worse left ventricular ejection fraction (β = -0.164, p = 0.006), and significantly correlate with levels of NT-proBNP (β = 3.263, p < 0.001), hs-Troponin T (β = 3.391, p < 0.001), high-sensitivity C-reactive protein (β = 2.472, p = 0.014) and heart failure (p= 0.002). Interestingly, common comorbidities such as chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m2, p = 0.004), diabetes mellitus (p = 0.001) and higher levels of glycated haemoglobin (HbA1c, β = 3.615, p < 0.001) showed also a significant association with sST2 levels. No significant association of sST2 was observed with arterial hypertension (p = 0.190), atrial fibrillation (p = 0.289), obesity (BMI ≥ 30 kg/m2, p = 0.302), sleep apnoea (apnoea-hypopnoea index ≥ 15/h, p = 0.068), peripheral artery disease (p = 0.823), or previous stroke (p = 0.861). Conclusion(s) Circulating levels of sST2 significantly correlate with heart failure, NT-proBNP, hs-TnT, and hs-CRP in patients with severe CAD. Additionally, sST2 levels were found to be elevated in patients with diabetes mellitus and chronic kidney disease.

Cardiovascular magnetic resonance to differentiate veteran athlete's heart with cavity dilatation and mild dilated cardiomyopathy

Abstract Introduction Endurance athletic training may lead to left ventricular (LV) dilatation and mildly reduced resting LV function which can be difficult to differentiate from dilated cardiomyopathy (DCM). Myocardial fibrosis is increasingly recognised in lifelong athletes and is also prevalent in DCM where it confers adverse prognosis.(1,2) However, it is unknown whether the pattern and prevalence of fibrosis in athletes with cavity dilatation differs from DCM. In this study, we compared the CMR fibrosis distribution and tissue characteristics between athletic LV dilatation and mild DCM patients. Methods We prospectively recruited 113 males; 64 endurance athletes and 49 mild DCM patients. Inclusion criteria Age 50-80 years, LVEF 45-54% and LV end-diastolic volume indexed to body surface area (LVEDVi)≥110ml/m2. Athletes trained≥10 weekly hrs for≥15 yrs. Exclusion criteria; Chest pain, prior coronary revascularisation, severe valvular disease, myocarditis, hypertrophic cardiomyopathy, inducible ischaemia or myocardial infarction on CMR. CMR protocol included volumetric assessment, T1 mapping, quantitative stress perfusion and quantitative late gadolinium enhancement. Statistical analysis between groups was performed using unpaired t-test and receiver-operator curve (ROC) analysis. Results LVEDVi was not significantly different between athletes and mild DCM patients (123.3±12.6 vs 129.8±23.1ml/m2, P=0.057). However, LVEF (52.0±6.1 vs 47.6±5.2%, P<0.001) and right ventricular (RV) EDVi (121.0±14.3 vs 97.6±25.2ml/m2, P<0.001) were both greater in athletes. There was no difference in non-ischaemic fibrosis prevalence between both groups (50.0 vs 49.0%, P=0.915) nor the burden of fibrosis (3.5±2.9 vs 7.4±12.0g, P=0.087). However, the distribution of fibrosis varied with a significantly greater prevalence of basal mid-myocardial inferolateral fibrosis amongst athletes (87.5 vs 50.0%, P=0.002) whereas basal mid-myocardial inferoseptal fibrosis was significantly more common in mild DCM (45.8 vs 9.4%, P=0.002). Native T1 (1249.0±38.1 vs 1308.3±47.1ms, P<0.001) and extracellular volume (ECV) (22.0±2.1 vs 25.9±3.5%, P<0.001) were both lower in athletes than mild DCM patients. Furthermore, athletes had higher myocardial perfusion reserve (MPR) (3.65±1.30 vs 2.76±0.92, P<0.001) and stress myocardial blood flow (MBF) (2.09±0.70 vs 1.62±0.66, P<0.001). On ROC analysis, native T1 (area under curve (AUC) 0.89, P<0.001), ECV (AUC 0.85, P<0.001) and stress MBF (AUC 0.68, P<0.001) were able to differentiate athletes and mild DCM. Native T1 and ECV were significantly better at discriminating than MPR (P<0.001). Conclusion Myocardial fibrosis was highly prevalent in both veteran endurance athlete's heart and mild DCM whilst its distribution was distinctive between the groups. Native T1 and ECV were the best discriminators. Recognition of fibrosis patterns and associated tissue characteristics may be clinically useful to differentiate these two overlapping phenotypes.Figure 1; LGE distribution in athletes cFigure 2; CMR tissue characteristics to

Development and Multinational Validation of an Ensemble Deep Learning Algorithm for Detecting and Predicting Structural Heart Disease Using Noisy Single-lead Electrocardiograms.

AI-enhanced 12-lead ECG can detect a range of structural heart diseases (SHDs) but has a limited role in community-based screening. We developed and externally validated a noise-resilient single-lead AI-ECG algorithm that can detect SHD and predict the risk of their development using wearable/portable devices. Using 266,740 ECGs from 99,205 patients with paired echocardiographic data at Yale New Haven Hospital, we developed ADAPT-HEART, a noise-resilient, deep-learning algorithm, to detect SHD using lead I ECG. SHD was defined as a composite of LVEF<40%, moderate or severe left-sided valvular disease, and severe LVH. ADAPT-HEART was validated in four community hospitals in the US, and the population-based cohort of ELSA-Brasil. We assessed the model's performance as a predictive biomarker among those without baseline SHD across hospital-based sites and the UK Biobank. The development population had a median age of 66 [IQR, 54-77] years and included 49,947 (50.3%) women, with 18,896 (19.0%) having any SHD. ADAPT-HEART had an AUROC of 0.879 (95% CI, 0.870-0.888) with good calibration for detecting SHD in the test set, and consistent performance in hospital-based external sites (AUROC: 0.852-0.891) and ELSA-Brasil (AUROC: 0.859). Among those without baseline SHD, high vs. low ADAPT-HEART probability conferred a 2.8- to 5.7-fold increase in the risk of future SHD across data sources (all P<0.05). We propose a novel model that detects and predicts a range of SHDs from noisy single-lead ECGs obtainable on portable/wearable devices, providing a scalable strategy for community-based screening and risk stratification for SHD.

P144 PHENOTYPIC CHARACTERISATION OF HEART FAILURE WITH PRESERVED EJECTION FRACTION ACCORDING TO BODY MASS INDEX: SUBANALYSIS OF THE ARGENTINE ARFEY-PRESER REGISTRY

Background: Nutritional status, characterised by body mass index (BMI), may influence therapeutic decisions in heart failure with preserved ejection fraction (HFpEF). The objectives of this study were to identify clinical and echocardiographic characteristics associated with nutritional status and to analyse therapeutic strategies in HFpEF patients in Argentina. Materials and Methods: This prospective, multicentre observational registry enrolled outpatients or those discharged from hospitals, with prior informed consent. The study spanned from December 2022 to February 2024. Inclusion criteria were: 1) presence of current signs and symptoms, LVEF ≥50%, 2) structural heart disease with LVH, LAE, or average E/e’ ≥15 on Doppler, 3) elevated natriuretic peptides: sinus rhythm: NTproBNP &gt;125 pg/ml or BNP &gt;35 pg/ml; Atrial fibrillation/flutter: NTproBNP &gt;375 pg/ml or BNP &gt;105 pg/ml; and 5) commitment to 6-month and 1-year follow-ups. Exclusion criteria comprised: 1) acute coronary syndrome, 2) coronary artery bypass grafting, or valve replacement within the preceding 3 months, 3) confirmed infiltrative or hypertrophic cardiomyopathy, severe valvular disease, 4) severe illness with &lt;1-year prognosis, and chronic renal failure on permanent dialysis. Results: A total of 449 patients were enrolled, with 440 having available BMI data for this analysis. Patient enrolment was consistent across centres and nationwide. BMI analysis revealed 0.7% undernutrition, 16.6% normal weight, 32% overweight, and 50.7% obesity. In Figure1 showed the analysis of clinical, laboratory, echocardiographic, and HF severity variables according to BMI. Significant differences were found in treatment, with lower use of RAS inhibitors and beta-blockers in non-normal weight patients compared to those with overweight and obesity. Conclusions: For a similar HFpEF severity profile, the phenotype according to BMI suggests different clinical characteristics. Underweight/normal weight patients were older, with more LAE and pulmonary hypertension, and fewer risk factors. Obesity was present in half of the cases, characterised by younger patients with a high burden of cardiovascular risk factors. This impacts the use of certain heart failure medications.

Impact of left atrial strain on clinical outcomes in patients with permanent pacemaker implantation.

This study aimed to investigate the clinical impact of pre-procedural left atrial strain (LAS) in patients undergoing permanent pacemaker implantation (PPI). This single-centre retrospective study enrolled 434 patients who were admitted for transvenous PPI between 2010 and 2020. After excluding patients with persistent atrial fibrillation, PPI for complete atrioventricular block, severe valvular disease, history of open-heart surgery and those without LAS data, 172 patients were analysed. The LAS was measured using commercially available software to calculate the average strain value of the apical four- and two-chamber views before PPI. The primary composite endpoint was hospitalization due to heart failure or cardiovascular death. Cox proportional hazard models were used to evaluate risk factors for the primary composite endpoint. The mean patient age was 78±8years, and 42% of the patients were men. PPI was performed for sick sinus syndrome in 64% and second-degree atrioventricular block in 36% of the patients. The pre-procedure left atrial reservoir strain (LASr) was 28±11%. The median follow-up period was 4.7years, and the primary endpoint was observed in 23 (13%) patients. In multivariate Cox proportional risk analysis, LASr was independently associated with the primary composite endpoint (hazard ratio, 1.08 per 1% decrease; 95% confidence interval, 1.02-1.15; P=0.007). The receiver operating characteristic curve of the LASr for the primary composite endpoint showed a cutoff value of 21% (area under the curve 0.657, P=0.004). The prognostic impact of LASr was consistent with that of sick sinus syndrome and atrioventricular block. A decreased pre-procedure LASr was associated with long-term adverse outcomes after PPI use.

Tricuspid regurgitation in the context of severe left-sided valvular disease: Patients characteristics and outcome

BackgroundWe aimed to assess the characteristics, management and long-term prognosis of a cohort of patients with multiple valvular disease, focusing on the context of severe mitral or aortic disease with concomitant significant tricuspid regurgitation (TR). MethodsAfter using a propensity score matching for age, 975 patients with ≥ moderate TR, diagnosed at our centers from 2012 to 2020, were included and divided in four groups, including isolated TR patients as reference group. Primary endpoint was all-cause death (ACD), secondary endpoint was the composite of heart failure (HF) hospitalization + any valvular intervention. ResultsPatients with isolated TR (356, 37 %) had more history of atrial fibrillation and were more often asymptomatic and with preserved left-ventricular ejection fraction (LVEF). Patients with severe mitral regurgitation (MR) + TR (466, 48 %) showed higher rates of concomitant coronary artery disease, advanced functional class symptoms and larger left atrial volumes. Severe aortic stenosis (AS) patients (131, 13 %) were older, with more comorbidities and lower LVEF. Patients with severe aortic regurgitation and TR (22, 2 %) were younger, with larger LV dimensions and higher pulmonary arterial pressures.After a median follow-up of 2.8 years, both endpoints were univariably more frequent in patients with severe AS + TR (all p < 0.001), but after comprehensive adjustment difference in the primary endpoint became insignificant, underscoring the serious outcomes of all significant TR groups significantly. Overall, in 44 (5 %) patients tricuspid intervention was performed, with no differences between groups in term of frequency of concomitant or staged tricuspid valve surgical treatment. ConclusionsIn the context of severe left-sided VD, concomitant significant TR is common, and each subtype presents with different clinical and echocardiographic features: patients with severe AS and TR have considerable worse prognosis, although comprehensive adjustment reflected the poor outcomes affecting all types of patients with significant TR. In this scenario, TR was profoundly undertreated.

Preliminary results from the Polish Infective Endocarditis Registry (POL-ENDO): Time to change clinical practice?

Infective endocarditis (IE) is a severe valvular disease associated with high morbidity and mortality. This preliminary study aimed to evaluate patient profiles and treatment outcomes of IE in Poland and compare them with European IE characteristics. We conducted a prospective multicenter observational cohort study - the POL-ENDO registry - in IE patients from 134 hospitals in Poland recruited between August 2022 and August 2023. We evaluated demographic, clinical, imaging, and treatment outcome data. A comparison of the Polish patients with those assessed in the EURO-ENDO registry between January 2016 and March 2018 was performed. Of a total of 880 IE patients, 622 were male (70.7%). The POL-ENDO participants were older (61.4 [16.7] years vs. 59.25 [18.03] years; P = 0.001). Native-valve IE occurred more often in Poland (82.3% vs. 56.6%; P <0.001). Transthoracic echocardiography was performed more frequently in Poland (93.6% vs. 89.8%; P <0.001). New imaging techniques (computed tomography/magnetic resonance imaging/positron emission tomography/single-photon emission computed tomography) were less frequently used in Poland (computed tomography: 41.3% vs. 53.2%; P <0.001; magnetic resonance imaging: 6.4% vs. 18.7%; P <0.001). Heart failure occurred more often in Poland as an in-hospital complication (31.4% vs. 14.1%; P <0.001). Surgical treatment was less frequently performed in Poland (36.9% vs. 51.2%; P <0.001). In-hospital mortality was higher in Poland (21% vs. 17%; P = 0.008). Polish IE patients were significantly older and had more comorbidities. New imaging techniques are less frequently used in Poland. Echocardiography was performed more frequently in Poland as the diagnostic mainstay. Surgical treatment was significantly less frequent in Poland. In-hospital mortality in Poland is higher.

Dilated Cardiomyopathy in the Cardiology Department of the CHU of Casablanca: A One-Year Observational Study

Dilated Cardiomyopathy (DCM) is defined by a left ventricle (LV) with reduced systolic function (&lt;45%) and dilation (LV volume &gt; 90 ml/m²), excluding coronary artery disease or sufficient load conditions to explain it. The etiologies are multiple and increasingly well-known. We conducted a single-centre, retrospective observational study within the cardiology department of the CHU IBN ROCHD in Casablanca, Morocco, over one year. The main objective was to describe the characteristics and particularities of patients followed for DCM. The diagnosis is based only on echocardiography, after exclusion of an ischemic cause, severe valvular disease, and congenital heart disease. During the study, 44 patients were included, with a male predominance of 63.6% versus 36.4%. The average age was 60 ± 16.8 years. The initial presentation of cardiomyopathy showed that 73% of patients were admitted with heart failure (HF). The mean left ventricular ejection fraction (LVEF) was 30.2 ± 7.9%. Among the attributed etiologies, idiopathic DCM was the main cause reported in 59% of cases, followed by systemic lupus erythematosus (14%) and myocarditis (14%). In our sample, treatment was based on HF management, including beta-blockers, renin-angiotensin system blockers, SGLT2 inhibitors, and aldosterone antagonists. Implantation of a defibrillator for primary prevention concerned only one patient (3%) of the 33 patients for whom the theoretical indication was retained.

Real-world barriers to CAR-T access: A Canadian referral center perspective.

e19002 Background: CD19 chimeric antigen receptor T-cell (CAR-T) is the standard of care for patients with relapsed or refractory large B-cell lymphoma (LBCL) beyond second line therapy. Access to CAR-T remains a significant barrier for patients and is limited by the numbers of CAR-T centers, patient comorbidities and lymphoma kinetics. This study aims to define clinical features associated with CAR-T ineligibility and associated outcomes in a real-world setting. Methods: We conducted a single center retrospective study of all adult patients with R/R LBCL referred at Hôpital Maisonneuve-Rosemont in Montreal, Canada, for CAR-T between July 2019 and December 2023. Comprehensive data were gathered from electronic medical records. This study was approved by the institutional ethics committee. Results: A total of 235 patients were evaluated: 133 (57%) were infused, 10 (4%) were apheresed but not infused and 92 (39%) patients were deemed ineligible and further analyzed. The main reasons for ineligibility were ECOG performance score more than 1 (n=23), comorbidities (n=18), not R/R to two prior lines of therapy (LOT) (n=15) and rapid disease progression (n=15). Prohibitive comorbidities included: creatinine clearance &lt;45ml/min (n=13), left ventricular ejection fraction &lt;45% (n=2), unstable coronary artery disease (n=1), severe valvular disease (n=1) and Child B cirrhosis (n=1). 10 declined CAR-T and 10 were diagnosed or had lymphoma subtypes not covered by CAR-T reimbursement criteria: grade 3B follicular lymphoma (n=5), T-cell lymphoma (n=2), Hodgkin lymphoma (n=1), Richter from chronic lymphocytic leukemia (n=1) and transformed marginal zone lymphoma (n=1). 33 had more than one exclusion criteria. Median age at referral was 66 years (range: 25-87). Median IPI at diagnosis (available in 74%) was 3 (range: 0-5). At CAR-T evaluation, 77 patients had a stage 3 or 4 disease and 7 had CNS involvement. Median LOT for LBCL were 2 (range: 0-5), 46 were primary refractory and 23 relapsed within 12 months. 18 patients had undergone prior high dose therapy and autologous stem cell transplant (HDT-ASCT). 6 were exposed to novel therapies (polatuzumab=6, mosunetuzumab=2). Median follow-up after CAR-T exclusion was 4.25 months (range: 0-49.2). 50 (68% of patients with B-cell lymphoma R/R to at least 2 LOT) were deceased at time of analysis. Data on further LOT was available for 22 patients: 10 received novel therapies (tafasitamab=5, polatuzumab=3, mosunetuzumab=1, alectinib=1), 6 HDT-ASCT, 3 allogeneic stem cell transplant, 4 conventional chemotherapies and 2 radiation therapy. Conclusions: 39% of evaluated patients with R/R LBCL were ineligible for CAR-T mainly due to poor performance status, comorbidities and prohibitive progressive disease. Our study did not capture patients not referred due to geographical considerations but highlights dismal outcomes for patients ineligible for CAR-T. Widespread access to novel therapies is awaited.

Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial

Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Impact of left bundle branch area pacing on right cardiac chambers dimensions and function. a medium term single center echocardiographic study

Abstract Introduction Left bundle branch area pacing (LBBAP) has become, in the last years, the preferred method for physiological pacing due to a wider target area, optimal pacing and sensing thresholds, and stable parameters over time. LBBAP ensures rapid and synchronous left ventricular (LV) activation through the left-sided conduction system. On the other hand, there is little data on right ventricular (RV) activation in LBBAP. The purpose of this study was to evaluate the impact of LBBAP on the right heart anatomy and function over a mid-term follow-up period. Material and methods All consecutive patients with successful LBBAP for bradyarrhythmic indications between February 2021 and July 2022 at our institution were eligible for this study. Left bundle branch capture was defined as a paced QRS complex of right bundle branch block morphology, and proof of transition from non-selective to selective capture with differential pacing maneuvers. To avoid confounders, patients with LV ejection fraction below 40% and with severe valvular disease were excluded. In the end, 57 patients were prospectively evaluated. Patient and procedural characteristics were recorded at baseline and follow-up. Also, right atrial (RA) volume, RV basal diameter, tricuspid annulus peak systolic elevation (TAPSE), RV S` wave (RVS`W), and tricuspid regurgitation (TR) were evaluated before the procedure and at the end of the follow-up period. Results The mean age of the patients was 68.9± 10 years, and 70% were males. 29.8% had a baseline right bundle branch block, and 22.8% had a left bundle branch block morphology. The baseline LV ejection fraction was 54.3 ± 9.9 %. The paced QRS duration was similar to the baseline values (128.5 ± 16.3 vs. 134.4 ± 30.4 msec, p=0.119). The pacing and sensing thresholds were 0.7 ± 0.3 V at 0.4 ms pulse duration and 9.7 ± 4.2 mV, respectively. The mean LV activation time (measured as the R wave peak time in V6) was 80.9 ± 12 msec, and the mean RV activation time (measured as the difference between QRS duration and LV activation time) was 51.9 ± 24.2 msec. The patients were followed over a mean period of 591.2 ± 150.3 days. There were no complications over the follow-up period that led to pacing interruption. The follow-up pacing (0.6 ± 0.2 V, p=0.003) and sensing (11.7 ± 6 mV, p= 0.023) thresholds showed significant improvement compared to the procedural values. The right heart echocardiographic evaluation showed non-statistically significant changes between the follow-up and the baseline values for RA volumes (57.9 ± 33.7 vs. 51.5 ± 28.4 ml, p=0.122), RV basal diameter (32.8 ± 5.4 vs. 31.8 ± 6.4 mm, p=0.31), RVS`W (12.8 ± 3.2 vs. 12.85 ± 2.7 cm/sec, p=0.933), and TR (1.8±0.8 vs. 2±1, p=0.07). On the other hand, there was a significant improvement in the TAPSE (22.2±4.3 vs. 20.7±3.6 mm, p=0.021). Conclusions LBBAP was associated with preserved dimensions and function of the right cardiac chambers over a medium-term follow-up period.

Abstract PO5-04-01: Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment

Abstract Objective: To explore the efficacy and safety of Inetetamab Combined with Sirolimus and Chemotherapy in the treatment of human epidermal factor receptor 2 (HER2) positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR (PAM) pathway after Trastuzumab treatment. Methods: This prospective multicenter clinical study enrolled HER2 positive metastatic breast cancer patients at the National Cancer Center in China from July 2021 to September 2022 with PAM pathway mutation confirmed by histology or peripheral blood genetic testing. The inclusion criteria included: 1) Recurrent and metastatic breast cancer patients with HER2 positive confirmed histologically; 2) ECOG PS score ≤ 2; 3) Patients who have progressed after previous treatment with Trastuzumab; 4) Patients with PAM pathway mutation confirmed by Genetic testing; 5) Patients' cardiac, pulmonary, liver and bone marrow functions are basically normal; 6) Patients voluntarily sign informed consent forms. The exclusion criteria included: 1) Patients previously treated with mTOR inhibitors or pyrotinib; 2) Patients who have used chronic Corticosteroid for more than 3 months or used Immunosuppressive drug within 4 weeks; 3) Patients with symptomatic central nervous system metastasis; 4) Patients with left ventricular Ejection fraction&amp;lt; 50% or clinical manifestations of obvious arrhythmia, myocardial ischemia, severe atrioventricular block, cardiac insufficiency, and severe valvular disease; 5)Diagnosed with other malignant tumors within five years. Patients were randomly divided into trial group and control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, and control group received pyrotinib and chemotherapy. RECISTv1.1 standard was used to evaluate the efficacy of patients. Descriptive statistics are used to summarize clinical pathological features. Kaplan Meier method was used to draw survival curves. Log-rank test was used to compare progression free survival (PFS) differences between groups. P&amp;lt; 0.05 was considered statistically significant. Results:A total of 59 HER2 positive metastatic breast cancer patients with abnormal activation of PAM pathway were included, of which 37 patients received the treatment of inetetamab group and 22 patients received the treatment of pyrotinib group. The median follow-up time was 5.33 months. In the intent-to-treat set, the median PFS of patients in the inetetamab group was 4.64 months, which was shorter than 5.69 months in the pyrotinib group. There was no statistically significant difference between the two groups (P=0.51; HR=0.41; 95% CI, 0.12-1.45). The objective response rate (ORR) of the inetetamab group and the pyrotinib group were 28.1% and 29.4%, respectively. In terms of safety, the incidence of adverse events (AE) in the experimental group was (33/37) 89.1%, while (16/21) 76.2% in the control group. The incidence of AE above level 3 in the inetetamab group and pyrotinib group were (13/37) 35.1% and (3/21) 14.3%, respectively. Conclusion:For the metastatic HER2 positive breast cancer patients with abnormal activation of PAM pathway treated with trastuzumab previously, the combination of inetetamab with sirolimus and chemotherapy regimen are equivalent to the combination of pyrotinib and chemotherapy regimen. It demonstrated that combination of inetetamab with sirolimus and chemotherapy could be one of the treatment options for the metastatic HER2 positive breast cancer patients. Citation Format: Qiao Li, Dan Lv, Xiaoying Sun, Mengyuan Wang, Li Cai, Feng Liu, Chenghui Li, Jiuda Zhao, Jing Sun, Yehui Shi, Fei Ma. Inetetamab combined with sirolimus and chemotherapy in HER2 positive metastatic breast cancer patients with abnormal activation of Pi3k/Akt/mTOR pathway after trastuzumab treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-01.

RELATIONSHIP BETWEEN NEUTROPHILTO HIGH-DENSITY LIPOPROTEIN CHOLESTEROL AND THE SEVERITY OF CORONARY STENOSIS IN PATIENT WITH CORONARY ARTERY DISEASE

Objective: Coronary artery disease (CAD) is a common cardiovascular disease related to atherosclerotic plaque formation. The Neutrophil to HDL-C ratio (NHR) reflects the inflammation process and dyslipidemia, affecting the atherosclerosis pathophysiology. This study aims to evaluate the relationship between NHR and the severity of coronary stenosis in CAD patients. Design and method: A prospective study with in-hospital follow-up in all patients admitted to Cardiology Center - Hue Central Hospital, whose were diagnosed with coronary artery disease between April 2023 and February 2024 were enrolled. The diagnostic criteria of CAD according to the recommendation of the Vietnam National Heart Association 2022. All patients received a comprehensive clinical examination and laboratory tests: complete blood count, high-sensitive Troponin-T, Total Cholesterol, HDL-Cholesterol, 12-leads EKG, transthoracic echocardiogram. All patients were undergone coronary angiography with doctor recommendation or self-requirement. Patients with history of coronary artery interventions, either balloon or stenting, or patient with history of coronary artery bypass graft were excluded from the study. Patients with acute or chronic infection state, end-stage kidney failure, end-stage renal disease, severe heart failure, severe valvular diseases and hematology diseases, patients being used corticosteroid therapy were also excluded. Results: Mean age was 67.12 ± 11.39 years, 58.5% male. The mean NHR increased according to Gensini score subgroups (p &lt; 0,01). Compared to the group with unincreased hs-Troponin (4.38 ± 1.56), the group with increased hs-Troponin showed a significantly higher mean NHR (6.14 ± 3.17) (p &lt; 0.01). There was a moderate correlation between NHR and Gensini score with r = 0.343, p&lt;0.01. NHR demonstrated moderate ability to predict patients with significant narrowing of coronary branches with the AUC= 0.727. With the NHR at 5.324, NHR has 54.2% in sensitivity and 83.3% of specificity in predicting of the significant coronary artery stenosis. Conclusions: Our study demonstrated there was a moderate correlation between Neutrophil to HDL-C ratio (NHR) and Gensini score. Neutrophil to HDL-C ratio (NHR) demonstrated moderate ability to predict patients with significant narrowing of coronary branches.

Percutaneous Tricuspid Valve Repair: The Triclip.

Tricuspid regurgitation is an often overlooked, but severe cardiac valvular disease associated with significant morbidity and poor quality of life. Tricuspid valve surgery is the only treatment that prevents progression of the disease but is often complicated or made impossible by perioperative risk factors. Due to the high-risk nature, tricuspid valve surgery is typically only done for severe tricuspid regurgitation at the time of left heart surgery, leaving many patients untreated. Medical therapy is limited primarily to diuretic agents, which are often unsuccessful in alleviating symptoms. Treatment of tricuspid regurgitation with transcatheter edge-to-edge repair has emerged after the success of this technique in mitral valve pathologies. This percutaneous procedure parallels surgical principles previously used for valve repair but eliminates the need for cardiac surgery, thus having the potential to serve as an alternative treatment in high-risk patients. The TriClip (Abbott Labs) device is an example of this therapy and the subject of this review.

A synergistic strategy based on active hydroxymethyl amine compounds and fucoidan for bioprosthetic heart valves with enhancing anti-coagulation and anti-calcification properties

With an aging population, the patients with valvular heart disease (VHD) are growing worldwide, and valve replacement is a primary choice for these patients with severe valvular disease. Among them, bioprosthetic heart valves (BHVs), especially BHVs trough transcatheter aortic valve replacement, are widely accepted by patients on account of their good hemodynamics and biocompatibility. Commercial BHVs in clinic are prepared by glutaraldehyde cross-linked pericardial tissue with the risk of calcification and thrombotic complications. In the present study, a strategy combines improved hemocompatibility and anti-calcification properties for BHVs has been developed based on a novel non-glutaraldehyde BHV crosslinker hexakis(hydroxymethyl)melamine (HMM) and the anticoagulant fucoidan. Besides the similar mechanical properties and enhanced component stability compared to glutaraldehyde crosslinked PP (G-PP), the fucoidan modified HMM-crosslinked PPs (HMM-Fu-PPs) also exhibit significantly enhanced anticoagulation performance with a 72 % decrease in thrombus weight compared with G-PP in ex-vivo shunt assay, along with the superior biocompatibility, satisfactory anti-calcification properties confirmed by subcutaneous implantation. Owing to good comprehensive performance of these HMM-Fu-PPs, this simple and feasible strategy may offer a great potential for BHV fabrication in the future, and open a new avenue to explore more N-hydroxymethyl compound based crosslinker with excellent performance in the field of biomaterials.

Sex differences in the association between epicardial adipose tissue volume and left atrial volume index

BackgroundSex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated.MethodsConsecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses.ResultsIn overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men.ConclusionsWe evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

Pulmonary artery sarcoma and severe valvular diseases in late-septuagenarian women: was 2-stage surgery an appropriate strategy? A case report

BackgroundPulmonary artery sarcomas (PASs) are rare, and complete tumor resection is often difficult at the time of detection. We encountered a case of PAS that was thought to be resectable; however, the patient had severe symptomatic valvular disease. We faced a difficult decision regarding the surgical strategy.Case presentationA 76-year-old female presented with a history of polysurgery for multiple primary cancers. She was referred to our department with a calcified mass in the right pulmonary artery (PA) and severe symptomatic valvular disease. After a discussion with the cardiovascular surgeon, we decided to perform a two-stage surgery. She underwent valvuloplasty through a median sternotomy, resulting in an improvement in her exertional dyspnea. The tumor was removed three months later with a right upper lobectomy and PA patch reconstruction through a posterolateral thoracotomy. When the PA was opened, the edge of the tumor was entrapped by vascular clamp forceps because of insufficient dissection of the adhesions between the superior vena cava and the right main PA resulting from the first operation. The patient underwent proton therapy twice for chest wall metastases which recurred three months after surgery, and local recurrence in the PA was diagnosed five months after surgery. The patient was alive with stable disease 25 months after surgery.ConclusionTwo-stage surgery for PAS and valvular disease resulted in incomplete resection of the PAS in the right PA. It is important not to underestimate surgical adhesions due to the initial surgery and to consider and implement measures to prevent adhesions of critical vessels during the second operation.