Prognostic Benefit Research Articles

Association Between Melanoma Metastasis and Metabolic Syndrome: A Cross-Sectional Study in a Chinese Population.

Metabolic syndrome (MetS) remains a significant global public health concern. However, the relationship between MetS, its individual components and melanoma metastasis remains unexplored. We analysed the clinical data of 258 Chinese melanoma patients who had not undergo systemic therapy. Binary logistic regression, adjusted for sex and age, was employed to evaluate the connection between MetS and its components and melanoma metastasis. Of the 258 melanoma patients, 92 met the MetS criteria upon diagnosis. No direct association between MetS and melanoma metastasis was identified. However, specific components of MetS, namely low HDL-cholesterol levels (OR = 2.85, 95% CI:1.50-5.41, p < 0.05) and dysglycaemia (OR = 4.23, 95% CI:1.80-8.96, p < 0.05), were associated with melanoma metastasis. In subgroup analysis, hypertriglyceridemia correlated with melanoma metastasis in non-elderly patients (< 65 years) (OR = 2.69, 95% CI: 1.14-6.33, p < 0.05). Central obesity and hypertension showed no association. A dose-response analysis further indicated that melanoma metastasis risk escalated with increasing fasting blood glucose and blood triglyceride concentrations, and with decreasing blood HDL concentration. Our results suggest that monitoring and managing individual components of the MetS, particularly HDL-cholesterol levels, fasting glucose and triglyceride levels, may have potential prognostic benefits for melanoma in the Chinese population.

Better pre-transplant treatment options for TP53-mutated MDS: cytoreductive or non-cytoreductive therapy?

Patients with TP53-mutated myelodysplastic neoplasms (MDS) have unfavorable prognoses; the benefit of cytoreductive treatment before hematopoietic stem cell transplantation (HSCT) is debated. We retrospectively analyzed 284 MDS patients undergoing allogeneic HSCT; among which 49 had TP53 mutation, with 38 receiving cytoreduction and 11 treated exclusively with best supportive care (BSC) before transplantation. Regardless of TP53 allelic state, patients with mutated-TP53 had a lower overall survival rate and higher relapse rate than those with wild-type TP53 (P < 0.001, P = 0.002, respectively). Among the TP53-mutated cohort, the 2-year overall survival rate in the cytoreduction group was comparable to that in the BSC group (34.6% vs. 45.5%, P = 0.53), and no other prognostic benefit was observed as well(all P < 0.05). Moreover, no prognostic difference was found among the chemotherapy subgroup, hypomethylating agent subgroup, and BSC subgroup(all P > 0.05). Patients in the pre-HSCT measurable residual disease (MRD) negative subgroup, pre-HSCT MRD-positive subgroup, and BSC subgroup exhibited similar prognoses (all P > 0.05). Multivariate analyses showed that pre-HSCT cytoreduction was not associated with post-transplant survival (all P > 0.05). In conclusion, TP53-mutated MDS patients have poor post-HSCT outcomes; compared to BSC, pre-HSCT cytoreduction doesn't improve prognosis, even in those with MRD negative before transplantation.

Abstract 4125999: Elderly patients with HF with reduced ejection fraction and renal failure: are SGLT2i a good option?

SGLT-2 receptor inhibitors (SGLT-2i) have been shown to reduce cardiovascular mortality and hospitalisations for heart failure (HF) in patients with HF with reduced ejection fraction (HFrEF) and to have a nephroprotective role in patients with chronic kidney disease (CKD). However, the available evidence in patients older than 75 years and with CKD is limited. We conducted a retrospective, single-centre study including patients aged &gt;75 years diagnosed with HFrEF (defined as ejection fraction &lt;40%), CKD (eGFR &lt;60mL/min) and with an indication for treatment with SGLT-2i for HF between November 2019 and November 2022. Clinical, analytical, electrocardiographic and echocardiographic variables were collected. A total of 173 patients were included with a mean follow-up of 31.6 months (SD ±13.2). Mean age 84.7 years (SD ±4.9), 66.5% were male, 85.5% were hypertensive, 34.7% diabetic and 39.3% dyslipidaemic. Peripheral vascular disease was present in 11.6%. Mean glomerular filtration rate was 45.9 mL/min and only 2.3% were on haemodialysis. LVEF at inclusion was 29.5% (SD ±7.9), with 53.1% being of ischaemic aetiology and the most frequent functional class being NYHA II (53.2%). Thirty-seven percent had atrial fibrillation and 34.1% had complete left bundle branch block. At the end of follow-up 80.3% were on beta-blockers, 48.6% on ACE inhibitors, 37.6% on aldosterone antagonists, 23.7% on ARNI and only 11% on SGLT-2i. Survival analysis was performed using Cox logistic regression (multivariate analysis), where SGLT-2i was shown to be the only protective factor for all-cause mortality (HR 0.3 [0.1-0.9]). Male sex (HR 2.2 [1.3-3.9]) and diabetes (HR 1.6 [1.0-2.6]) were associated with higher mortality. The attached figure (figure 1) shows the Kaplan-Meier survival curves for total mortality in those patients with and without SGLT-2i (p log-rank 0.05). In our population, SGLT2i showed a significant reduction in total mortality in patients older than 75 years, with HFrEF and CKD. However, the treatment rate in this subgroup of patients is very low. Further implementation of SGLT2i treatment in this type of patient could be of significant clinical and prognostic benefit.

EPID-28. TRENDS IN LOW GRADE GLIOMA PROGNOSIS AND THE EVOLVING IMPACT OF GROSS TOTAL RESECTION ACROSS FIFTY YEARS: A MULTICOHORT ANALYSIS

Abstract OBJECTIVE Significant advancements in neurosurgical planning, approach, and practice over the past five decades have improved the surgical management of diffuse low and high-grade gliomas. We sought to evaluate the extent to which LGG survival outcomes have evolved over the past fifty years using glioma registry datasets with histopathological groups defined by WHO diagnostic criteria and supplemented with next generation genome-sequencing. METHODS Three datasets (SEER, TCGA, and GENIE) were used to evaluate trends in prognosis following LGG diagnosis and resection between 1975 and present (GBM as a comparator cohort). The primary outcomes evaluated were longitudinal disease-specific survival and overall survival, with secondary fixed-timepoint outcomes evaluated at 12-months, 24-months, and 60-months. Subjects from SEER were categorized by histology, while subjects from TCGA and GENIE were included based IDH mutation status with available histopathology. RESULTS A total of 39,958 adult patients were included. Overall survival increased for both LGG and GBM between 1975 and 2010, however only LGG outcomes continued to improve following 2010 (2010-; HR=0.955, 95%CI 0.926 to 0.986). Evaluation of the interaction between resection extent and diagnosis year revealed a progressive increase in the survival benefit of GTR in recent years, particularly for LGG. Independent of other available clinical/molecular features and considering the interaction term between year of diagnosis and resection extent, the gap in independent prognostic benefit associated with GTR between LGG and GBM has significantly widened (2010-2020 vs 1990-2000, p&amp;lt;0.05). CONCLUSION Over the past three decades, consistent improvements in LGG outcomes were observed while prognosis following GBM diagnosis has remained largely unchanged following 2010. Notably, we observed increasing prognostic value of achieving GTR particularly in patients with LGG.

Multiomics Characterization and Comprehensive Omics-Based Classification System in Adult Patients with B-Cell Acute Lymphoblastic Leukemia

ABSTRACT BACKGROUND: Adult B-cell acute lymphoblastic leukemia (B-ALL) is a highly heterogeneous disease with a challenging prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the cornerstone of treatment for these population. Previous B-ALL classifications have mainly relied on transcriptomics for prognosis prediction. However, a more comprehensive classification system integrating diverse subtypes with definite prognosis and therapeutic implications in adult B-ALLs is currently lacking. METHODS: We analyzed 391 adult B-ALL patients, including a real-world 88 cases (Ph positive 34, Ph negative 54), titled ‘ihCAMs-ALL’ (aged 34, 15-70), and two independent validation cohorts (GSE34861 N=194, Ph positive 78, Ph negative 116; GSE66005 N=109, Ph positive 42, Ph negative 67). Among ihCAMs-ALL, we conducted transcriptomic (RNA-seq), epigenetic methylation (Illumina 850K) and genomic mutation (Targeted NGS). In addition, 9 healthy donors and 9 patients with T-cell acute lymphoblastic leukemia (T-ALL) were enrolled for extensive omics-based comparisons. We classified patients based on multi-omics information by ten unsupervised algorithms and constructed the model called comprehensive omics-based classification system for B-cell ALL with therapeutic implications (COMBAT). RESULTS: B-ALL patients exhibited unique epigenetic (hypomethylated state compared to T-ALL patients) and gene expression landscapes (immunocompromised state compared to healthy controls). Next, we compared methylation and transcriptomic of Ph negative B-ALLs and T-ALLs, key active regulons that were uniquely found associated with B-ALL, including BACH2, EBF1, ELK3, HIVEP1, JUNB, and ZNF296 (all Spearman's coefficients &amp;gt; 0.8, all p &amp;lt; 0.001). These data demonstrated that both the similarities and heterogeneity within the B-ALLs. Next, we assessed the interplay between COMBAT clusters and clinical features. COMBAT stratified patients into three cohorts: (1) COMBAT1, characterized by high stem/myeloid antigen expression, low immune infiltration, endothelial cells enrichment, presented degraded hypomethylation in CIMP (CpG island methylator phenotype) ; (2) COMBAT2, defined as an inflamed subtype with immune exhaustion and activated inflammatory response pathways; and (3) COMBAT3, termed ‘proliferative subtype’, with MYC pathway activation and hypermethylation at enhancer regions in patients characterized by CIMP. In Ph-negative B-ALLs, diagnostic FACS data revealed that COMBAT3 subgroup patients presented lower expression of myeloid-associated antigens CD13 (p=0.002) and CD33 (p=0.013), as well as stem cell-associated antigens CD34 (p=0.004) and HLA-DR (p=0.012) than COMBAT1-2. Meanwhile, COMBAT1-2 demonstrated lower complete remission (CR) rates compared to COMBAT3 (0% vs. 50% vs. 96.2%, p=0.0028). Ph-negative B-ALL patients undergoing allo-HSCT in the COMBAT3 group showed better overall survival (OS) than those in the COMBAT1-2 groups (estimated 3-year OS: 100% vs. 65.6%, log-rank test, p=0.034), suggesting a prognostic benefit of this subtype. CONCLUSIONS: The COMBAT system redefines adult B-ALL subtypes, predicts immune characteristics, and delineates potential benefits from allo-HSCT for Ph-negative patients. These findings provide crucial insights into therapeutic options and outcomes for adult B-ALL patients, thereby enhancing our understanding of effective treatment strategies.

Controversias en la revascularización y el estudio de viabilidad miocárdica en el síndrome coronario crónico

The broad spectrum of patients with chronic coronary syndrome and the controversies in diagnosis and treatment pose a major challenge in clinical decision making. Concerning the diagnosis, the utility of myocardial viability study has been questioned by recent clinical trials. Regarding the therapeutic approach, in patients with simple coronary disease, percutaneous revascularization has proved its utility in anginal symptoms relieve, but the evidence regarding a prognostic benefit is contradictory. In complex coronary disease, coronary artery bypass grafting surgery has reported better results than percutaneous intervention. Besides, surgical revascularization has demonstrated a reduction in cardiovascular events over medical treatment in patients with ischemic left ventricular dysfunction. In this review we critically analyse the current evidence on viability study and myocardial revascularization in patients with chronic coronary syndrome.

Identification of Cuproptosis-Related Genes for Molecular Subtyping: Predicting Prognostic and Therapeutic Response in Glioma.

Cuproptosis, a metal-ion-dependent form of regulated cell death induced by copper overload, is emerging as a potential mechanism in high-grade glioma (HGG). Despite its significance, the role of cuproptosis in predicting the prognostic and therapeutic response in HGG remains poorly understood. We performed unsupervised clustering to stratify patients with HGG in the Chinese Glioma Genome Atlas (CGGA) according to the expression of 14 cuproptosis-related genes (CRGs) and validated in The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to explore the biologicalprocesses and pathways involved within distinct groups. We constructed the CupScore model to predict the responsiveness to immune checkpoint inhibitors (ICIs) therapy and chemotherapy in patients with HGG. Additionally, in vivo and in vitro experiments were performed to investigate the potential biological function of CDKN2A in HGG. We identified two cuproptosis-related molecular subgroups with significantly different survival probabilities. Patients with HGG in cluster 1 were characterized as immune-desert phenotype with higher CupScore and lower expression of MHC complex, interferons, chemokines, interleukins, and immune checkpoints. In contrast, cluster 2 showed an immune-inflamed signature. We screened PI-103 as the most promising candidate for patients with higher CupScore and confirmed its experimental evidence and clinical trial status. Patients with lower CupScore showed higher response rates to anti-PD-L1 and anti-PD1 combined with anti-CTLA4 ICI therapy. Furthermore, in vivo and in vitro experiments revealed that CDKN2A enhanced the malignant phenotype of HGG. Cuproptosis has the ability to reprogram the tumor microenvironment (TME) in HGG, leading to the stratification of patients into two distinct molecular subgroups. The CupScore model emerged as a robust metric for predicting the prognostic and therapeutic benefits, as well as may therefore facilitate personalized treatment strategies for patients with HGG.

Systemic chemotherapy improves outcome of hepatocellular carcinoma patients treated with transarterial chemoembolization

BackgroundTransarterial chemoembolization (TACE) based neoadjuvant therapy was proven effective in hepatocellular carcinoma (HCC). Recently, tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) also showed promise in HCC treatment. However, the prognostic benefits associated with these treatments remain uncertain. This study aimed to explore the relationship between pathologic response and prognostic features in HCC patients who received neoadjuvant therapy. MethodsHCC patients who received TACE either with or without TKIs/ICIs as neoadjuvant therapy before liver resection were retrospectively collected from the First Affiliated Hospital, Zhejiang University School of Medicine in China. Pathologic response was determined by calculating the proportion of non-viable area within the tumor. Major pathologic response (MPR) was defined as the presence of non-viable tumor cells reaching a minimum of 90 %. Complete pathologic response (CPR) was characterized by the absence of viable cells observed in the tumor. ResultsA total of 481 patients meeting the inclusion criteria were enrolled, with 76 patients (15.8 %) achieving CPR and 179 (37.2 %) reaching MPR. The median recurrence-free survival (mRFS) in the CPR + MPR group was significantly higher than the non-MPR group (31.3 vs. 25.1 months). The difference in 3-year overall survival (OS) rate was not significant (90.2 % vs. 87.6 %). Multivariate Cox regression analysis identified failure to achieve MPR (hazard ratio = 1.548, 95 % confidence interval: 1.122–2.134; P = 0.008), HBsAg positivity (HR = 1.818, 95 % CI: 1.062–3.115, P = 0.030), multiple lesions (HR = 2.278, 95 % CI: 1.621–3.195, P < 0.001), and baseline tumor size > 5 cm (HR = 1.712, 95 % CI: 1.031–2.849, P = 0.038) were independent risk factors for RFS. Subgroup analysis showed that 67 of 93 (72.0 %) patients who received the combination of TACE, TKIs, and ICIs achieved MPR + CPR. ConclusionsIn individuals who received TACE-based neoadjuvant therapy for HCC, failure to achieve MPR emerges as an independent risk factor for RFS. Notably, the combination of TACE, TKIs, and ICIs demonstrated the highest rate of MPR.

The effect of empagliflozin on right ventricular function in heart failure patients with reduced ejection fraction: analysis from the randomized empire hf clinical trial

Abstract Background Reverse remodeling of the left ventricle (LV) has been proposed as a key mechanism to the cardio-protective effects of sodium-glucose-transporter-2 (SGLT2) inhibitors in patients with heart failure and reduced ejection fraction (HFrEF). Deterioration of the right ventricular (RV) function is associated with poor outcome, whereas improvement in RV dysfunction has been correlated with improved outcomes in HFrEF patients. The impact of SGLT2 inhibitors on the RV remains unclear. Purpose The aim of this post-hoc study of the Empire HF trial was to investigate the effect of Empagliflozin on RV function assessed by echocardiography in patients with HFrEF after 12 weeks of treatment compared to placebo. Methods The Empire HF trial was a double-blind, placebo-controlled, randomized clinical trial, in which 190 stable HFrEF patients with a LV ejection fraction (LVEF) ≤40% were randomized (1:1) to receive Empagliflozin 10 mg once daily or matching placebo for 12 weeks. Echocardiographic images were analysed blinded to treatment allocation. Exploratory outcomes were changes in right ventricular function. Statistical analyses were performed using mixed-effects linear models adjusted for age, sex and baseline variables. Results Baseline characteristics were well balanced between the two groups; mean age 64 (SD±11) years; males: 85%; mean LVEF 29 (SD±8) %, RV free wall strain (RVFWS): -16.7 (SD±6)%, NYHA-functional class II: 78% and ischemic HFrEF etiology: 51%. No significant between-group differences were detected in RV free wall strain (RVFWS), tricuspid annular plane systolic excursion (TAPSE) or S’ RV free wall (all P&amp;gt;0.05), Figure 1. When stratified into baseline tertiles of RVFWS, patients in the lowest tertile showed a significant improvement in the Empagliflozin group compared to placebo (treatment effect: -4.4 % [95% CI: -8.0 to -0.8]; P=0.018), Figure 2. There was no correlation between the effect of Empagliflozin on RVFWS in the lowest RVFWS tertile and other changes such as LVEF (P=0.845), plasma volume (P=0.710) or weight loss (P=0.639). Conclusion In this randomized, short-term trial, Empagliflozin did exert a significant effect on RV function in stable HFrEF patients in the overall study population, but notably improved RVFWS in patients in the lowest tertile of RVFWS at baseline after 12 weeks of treatment. Additional research is required to confirm these explorative findings, and to better understand the impact of SGLT2i on RV function and identify patients who could potentially experience therapeutic and prognostic benefits by RV improvement.

Intravascular imaging-guided percutaneous coronary intervention according to lesion complexity

Abstract Background Recent trials have shown intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) has prognostic benefit compared with angiograph-guided PCI in complex coronary artery lesions. However, it is unclear whether this benefit is affected by overall complexity of target lesions in each patient. Objectives To investigate an impact of the number of complex lesion features on the benefit of IVI-guided PCI. Methods A total of 4,611 patients with complex coronary artery lesions from the RENOVATE-COMPLEX-PCI trial (n=1,639) and the institutional registry of a medical center (n=2,972) were classified according to the number of complex lesion features found in each patient. The primary outcome was a target vessel failure (TVF) at 3 years, a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. Results The best cut-off number of complex lesion features for the risk of TVF was 3 and patients with ≥3 complex lesion features had higher risk of TVF than those with &amp;lt;3 complex lesion features (11.0% vs. 7.2%; HR 1.59, 95% CI 1.28-1.96, P&amp;lt;0.001). IVI-guided PCI significantly reduced the risk of TVF compared to angiography-guided PCI in both groups (≥3 complex lesion features: 7.4% vs. 14.4%, HR 0.49; 95% CI 0.35-0.69, P&amp;lt;0.001; &amp;lt;3 complex lesion features: 5.7% vs. 8.1%; HR 0.72, 95% CI 0.53-0.98, P=0.039). The benefit of IVI-guided PCI tended to increase as the number of complex lesion features increased (absolute risk reduction for TVF: -0.012 vs. -0.027 vs. -0.055 vs. -0.077, respectively, for the number of complex lesion features 1 vs. 2 vs. 3 vs. ≥4, interaction P=0.048). Conclusion In patients with complex coronary artery lesions, IVI-guided PCI reduced the risk of TVF regardless of overall complexity of the target lesions in each patient. The prognostic benefit of IVI-guided PCI tended to increase as patients had more complex lesion features.Clinical Outcomes

Outcomes of implantable cardioverter-defibrillators in patients with a left ventricular assist device: a systematic review and meta-analysis

Abstract Introduction Implantable Cardioverter-Defibrillators (ICDs) improve survival in advanced heart failure with reduced ejection fraction (HFrEF) and prevent sudden cardiac death. However, the prognostic benefits of ICDs among patients with a Left Ventricular Assist Device (LVAD) remain uncertain and controversial. Therefore, we conducted a systematic review and meta-analysis to assess the effectiveness and safety of ICD implantation among LVAD recipients. Methods We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and EMBASE for the peer-reviewed articles published in English assessing the impact of ICD implantation among LVAD recipients, till 10/01/2024. ICD implantation was defined as implantation before LVAD, simultaneous implantation with LVAD, or within 30 days of LVAD insertion. Two independent review authors assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data in forest plots. The primary outcome was all-cause mortality associated with ICD implantation compared to no ICD implantation, and the secondary outcomes included ventricular arrhythmia (VT), and hemorrhagic stroke. Heterogeneity was assessed using Q test and I2, with I2 &amp;gt; 50% indicating marked heterogeneity. Results A total of 13 observational studies comprising 54571 recipients of LVAD were included in the analysis of the primary outcome. All-cause mortality was similar among patients with ICD versus no ICD (Odds Ratio [OR]= 0.77; 95% CI, 0.57-1.04, I2= 89%, P=0.09), as shown in Figure 1. Likewise, ICD implantation was associated with similar rates of VT and hemorrhagic stroke (VT: OR= 1.81, 95% Cl, 0.82-4.01, I2= 90%, P=0.14; hemorrhagic stroke: OR= 1.01, 95% Cl, 0.81-1.25, I2= 0%, P= 0.95). Conclusion Among patients with HFrEF and LVAD as advanced heart failure therapy, ICD implantation didn’t provide additional prognostic survival benefit, suggesting possible use of LVAD without ICD implantation.Figure 1.Forest plot of mortality

Long-term mortality outcomes of southeast asian patients with aortic stenosis

Abstract Background Limited data exists on mortality outcomes of aortic stenosis (AS) in Southeast Asians. Insights into this may confer prognostic benefits and affect therapeutic targets. Purpose Our study aims to provide insights into 10-year mortality outcomes and prognostic indicators of AS in this cohort. Methods Consecutive patients (n = 703) with echocardiographic diagnoses of AS at a tertiary academic hospital in Southeast Asia were studied. Demographics, co-morbidities and outcomes were collected. Multivariate Cox regression model was constructed. Results 55.2% (n = 388) of patients had mild AS, 29.3% (n = 206) had moderate AS, and 15.5% (n = 109) had severe AS. Out of 431 deaths, 35.8% (n = 86) of known cases were cardiovascular. The leading cause of cardiovascular mortality was coronary-linked in 20.8% (n = 50); 7.9% (n = 19) was valvular aortic stenosis; 2.5% (n = 6) was cardiac failure, 1.3% (n = 3) was sudden cardiac death, and 2.9% (n = 7) was ischaemic stroke. Of 154 (64.2%) non-cardiovascular mortality, sepsis caused 40% (n = 97) of deaths, malignancy in 11.7% (n = 28), renal failure in 5% (n = 12) and respiratory failure in 1.7% (n = 4). 44.3% (n = 191) of cases were unknown. Higher proportions of AS patients with cardiovascular death had hyperlipidaemia (p = 0.027) and coronary artery disease (p = 0.028). Multivariable Cox regression showed age (HR 1.041, 95% CI: 1.020-1.062, p &amp;lt; 0.001), anaemia (HR 2.121, 95% CI: 1.535-2.930, p &amp;lt; 0.001) and prior cardiovascular hospitalisation (HR 1.420, 95% CI: 1.040-1.938, p = 0.027) to be significant predictors of all-cause mortality. Aortic valve replacement was a significant protective factor of all-cause mortality after adjustments for age, gender, comorbidities, and echocardiographic findings (HR 0.313, 95% CI 0.131-0.747, p = 0.009). Conclusions Non-cardiovascular death was the leading cause of mortality in Southeast Asians with AS. Ischaemic heart disease was the commonest cause of cardiovascular mortality. Predictors of all-cause mortality included age, anaemia and prior cardiovascular hospitalisation. Valvular replacement was protective of all-cause mortality in AS.

The effect of transcatheter aortic valve implantation on fractional flow reserve and non-hyperemic pressure ratios

Abstract Background Coronary artery disease in patients undergoing transcatheter aortic valve implantation (TAVI) is a very frequent clinical issue. Complex coronary artery disease can negatively influence outcomes after TAVI, however, angiography-guided percutaneous coronary intervention (PCI) has not been shown to offer any prognostic benefit. Coronary pressure indices, to select which lesions need treatment, are promising but are currently underused in aortic stenosis (AS) patients due to many physiological pitfalls. Available studies are small and show conflicting results on the effect of transcatheter aortic valve implantation (TAVI) on these indices. Purpose The aims is to compare the effects of TAVI on fractional flow reserve (FFR) and Non-hyperemic pressure ratio’s (NHPRs). Both immediate and long-term effects were studied. Methods Lesion specific coronary pressure data was extracted from 6 studies resulting in 147 lesions for immediate change in FFR analysis and 105 for NHPR analysis. To investigate the long-term changes, 93 lesions for FFR analysis and 68 for NHPR analysis were found. Results Immediately after TAVI, FFR decreased significantly (-0.0130 ± 0.0406 standard deviation, p-value: 0.0002) while NHPR remained stable (0.0003 ± 0.0675, p-value: 0.9675). Long-term after TAVR, FFR decreased significantly (-0.0230 ± 0.0747, p-value:0.0038) while NHPR increased non-significantly (0.0166 ± 0.0699, p-value: 0.0543). This increase in NHPRs became significant when only borderline NHPR lesions were considered (0.0249 ± 0.0441, p-value: 0.0015). All other results were confirmed in borderline-only lesions. Conclusions TAVI caused small significant, but opposite, changes in FFR and NHPR. In AS, FFR might underestimate lesion significance while NHPRs might overestimate its significance. This is only clinically relevant in borderline lesions, clear positive or negative physiological assessments can be trusted.Figure 1Figure 2

Chronotropic incompetence predictors in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Chronotropic incompetence (CI) has been described in many patients after myocardial infarction (MI) and can negatively affect physical capacity, especially if negative chronotropic therapy (NCT) is prescribed. Prediction of CI after MI could be useful for tailored medical therapy and exercise training prescription. Purpose We aim to predict CI on initial exercise ECG testing (ExECG) in MI patients submitted to a Cardiac Rehabilitation Program (CRP). Methods Patients with ST-segment elevation MI (STEMI) or occlusion MI (OMI) submitted to our CRP were prospectively included. After an initial follow-up phase of clinical stabilization and medical therapy optimization, ExECG (conventional or cardiopulmonary) was performed. Peak VO2 and chronotropic reserve index [(maximum heart rate – resting heart rate) / ([220-age] – resting heart rate)] were measured. Chronotropic incompetence was defined as &amp;lt;80% chronotropic reserve index (≤62% in patients treated with NCT). Pharmacological therapy with NCT was registered in absolute and equivalent doses per bisoprolol 2.5mg units (B2.5EU). The effect of NCT on CI was studied by ANOVA test, and predictors of CI by binary logistic regression analysis. The model was tested by area under the curve (AUC) analysis in receiver operating characteristic curves. A p&amp;lt;0.05 was considered statistically significant. Results The cohort comprised 143 patients, mostly middle-aged (mean 60.3±15.8 years) males (85.3%) with anterior or inferior MI (44.8% and 44.8%, respectively). Mean left ventricular ejection fraction (LVEF) was 52.4±10.6% and 36.4% depicted LVEF&amp;lt;50%. NCT was prescribed in most patients (n=125, 87.4%), and median equivalent dose was 1 [0.5-1] B2.5EU. CI was noted on more than half of the population on initial ExECG (n=75, 52.4%). Higher NCT doses per B2.5EU associated with worse mean chronotropic reserve indexes: 72.8±24.4% in patients without NCT; 71.7±18.7% in patients with 0.5 B2.5EU; 62.8±18.2% in patients with 1 B2.5EU; and 58.7±16.9% in patients with ≥2 B2.5EU (ANOVA p=0.04). On binary logistic regression analysis, only two variables were independent predictors of CI: diabetes mellitus (HR 3.02 [1.26-7.23], p=0.01) and LVEF (0.97 [0.94-0.99] per increased %, p=0.04). However, the predictive power of the model was poor (AUC 0.62 [0.53-0.71], p=0.01). Conclusions Chronotropic incompetence after a MI is associated with lower LVEF, diabetes mellitus, and higher doses of NCT. Although significant interindividual variability exists in chronotropic response in the post-infarction period, these factors could be taken into consideration for tailored prescription (or deprescription), especially in patients who may not derive any prognostic benefit from NCT.Chronotropic incompetence in CRP

Real-life impact of complete revascularization of non-ST elevation myocardial infarction during index hospitalization

Abstract Introduction patients with non-ST elevation acute myocardial infarction (NSTEMI) frequently present multivessel disease (MVD) with significant stenosis in non-infarct-related arteries (non-IRA). Unlike for ST elevation acute myocardial infarction, there is a paucity of studies evaluating the prognostic impact of complete revascularization in these patients. In fact, recommendation for complete revascularization is based in observational and non-randomized studies suggesting a possible benefit regarding mortality and major cardiovascular events. Purpose to evaluate the prognostic impact of complete revascularization during the index hospitalization in the Portuguese patients with NSTEMI and MVD. Methods patients hospitalized for NSTEMI with MVD included in a national multicentre retrospective study between October 2010 and December 2022 were divided into two groups: group 1 was submitted to complete percutaneous revascularization during the index hospitalization (IRA and non-IRA with diameter stenosis ≥50% on angiography), and group 2 performed IRA-only revascularization. The impact of complete revascularization on the probability of cardiovascular re-hospitalization, as well as on in-hospital and one-year mortality rates was evaluated. Results a total of 3084 patients was included, 74.8% were males, with a mean age of 67.8±11.9 years. Most patients were submitted to IRA-only revascularization (72.9%). From the remaining, 81.4% performed complete revascularization during the index procedure and 18.6% staged during index hospitalization. Group 1 patients were younger (65.5±11.8 vs. 68.6±11.8 years, p&amp;lt;0.001), with fewer comorbidities and slightly higher left ventricular ejection fraction (55±11 vs. 51±11%, p&amp;lt;0.001). On the other hand, group 2 patients revealed a significantly higher percentage of previous, revascularization (14.8% vs. 1.6%), mostly surgical. Besides overall similar incidence of in-hospital complications, including recurrence of acute myocardial infarction, patients submitted to complete revascularization showed a non-significant trend to an inferior in-hospital mortality rate (0.7 vs. 1.6%, p=0.06). Also, 1-year mortality rate was similar between groups (4.2 vs. 5.0%, p=0.54). However, complete revascularization appeared to result in a long-term prognostic benefit, halving the incidence of unplanned cardiovascular re-hospitalizations at one year of follow-up (9.3 vs. 18.8%, p&amp;lt;0.001). Conclusion complete revascularization led to an overall long-term benefit, mainly due to a reduction in cardiovascular re-hospitalizations, without a significant impact on 1-year mortality rate.

Understanding the benefits of renin-angiotensin-aldosterone system inhibitors and influence of hyperkalaemia on their prescription: a UK survey of healthcare professionals' views and practice

Abstract Background Renin–angiotensin–aldosterone system inhibitors (RAASi) improve outcomes in heart failure with reduced ejection fraction (HFrEF) and they should be increased to the maximally tolerated dose. However, their use is often hindered by hyperkalaemia leading to discontinuation or down titration. Purpose Assess perceptions of primary and secondary healthcare professionals regarding benefits of RAASi according to indication and, in the context of developing hyperkalaemia, to identify barriers to optimal utilisation, and to explore options for improving management protocols, specifically in HFrEF. Methods An electronic survey was distributed in primary and secondary care setting in Hampshire, UK, to evaluate knowledge about benefits of RAASi, clinical response to varying level of potassium (K+), and decision-making using several clinical scenarios. Hyperkalaemia was graded into mild (serum K+ 5.5 – 5.9 mmol/L), moderate (serum K+ 6.0 – 6.4 mmol/L) or severe (serum K+ ≥ 6.5 mmol/L). Results Between November 2021 and January 2023, 300 questionnaires were completed by 274 (91%) physicians (varying grades of seniority), 22 (7%) non-medical prescribers, and 4 (1%) pharmacists. 80% were working in secondary care across different specialities (31 working in cardiology and 15 in nephrology). The majority were aware of prognostic benefit of angiotensin converting enzyme inhibitors (ACEi) in patients with HFrEF although this was lower for mineralocorticoid receptor antagonists (MRA) (Fig 1). Fewer than 2/3 of respondents were aware of impact of ACEi on symptoms. In the presence of mild hyperkalaemia, 75% and 88% of healthcare professionals would stop or reduce ACEi and MRA, respectively. In moderate or severe hyperkalaemia, this increased to 96% and 97%, respectively (Fig 2A-B). When considering the scenario of a patient with HFrEF who had ACEi stopped due to K+ 5.9 mmol/L, the potassium at which the responder would consider re-starting the ACEi ranged from 77% when potassium level &amp;lt; 5.5 mmol/L to 1% in moderate or severe hyperkalaemia (Fig 2C). 74% of healthcare professionals were familiar with local hyperkalaemia management protocol and 93% supported dedicated training on RAASi dose adjustment and hyperkalaemia management. Conclusion This survey, across a broad range of healthcare professionals, shows uncertainties around knowledge of benefits of RAASi in patients with HFrEF and there is sizeable variation in the prescribing response to degrees of hyperkalaemia. Given the voluntary nature of the survey, it is plausible that these data are biased towards individuals with greater understanding. Regardless, there is a need for continued education with a goal of improving patient-centred care.

Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis

Abstract Background Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking. Purpose The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR. Methods A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category. Results The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p &amp;lt;0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p &amp;lt;0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p &amp;lt;0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p &amp;lt;0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR. Conclusions RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR

Lack of incremental prognostic value of triglyceride glucose index beyond coronary computed tomography angiography features for major events

This study was aim to determine the prognostic value of triglyceride-glucose (TyG) index and coronary computed tomography angiography (CTA) features for major adverse cardiovascular events (MACE). In addition, we investigate the incremental prognostic value of TyG index beyond coronary CTA features in patients with suspected or known coronary artery disease (CAD). The present study ultimately includes 3528 patients who met the enrollment criteria. The TyG index was calculated based on measured levels of triglycerides and fasting blood glucose. Primary combined endpoint consisted of MACE, which defined as myocardial infraction (MI), all-cause mortality and stroke. Three multivariate Cox proportional hazard regression models were performed to assess the association between TyG index and MACE. C-statistic was performed to assess the discriminatory value of models. 212 (6.0%) patients developed MACE during a median follow-up of 50.4 months (IQR, 39.4–55.1). TyG index remained to be a significantly and independent risk factors for predicting MACE after adjusting by different models (clinical variables alone or plus coronary CTA features) in multivariable analysis. Both the addition of TyG index to clinical model plus Coronary Artery Disease Reporting and Data System (CAD-RADS) and to clinical model plus CAD-RADS 2.0 slightly but not significantly increased the C-statistic index (0.725 vs. 0.721, p = 0.223; 0.733 vs. 0.731, p = 0.505). TyG index was associated with an increased risk of MACE. However, no incremental prognostic benefit of TyG index over CAD-RADS or CAD-RADS 2.0 was detected for MACE in patients with suspected or known CAD.

The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions

Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLSs) within ovarian tumors are less developed compared with TLSs in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLSs and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.

Long term follow-up of bilateral internal thoracic artery use in young coronary artery bypass grafting patients: 29 year single surgeon experience.

Improved long term survival has demonstrated by grafting left internal thoracic artery (LITA) to the left anterior descending artery (LAD). This study investigated the prognostic benefits of BITA versus single LITA with common anastomotic configurations of BITA. Elective patients age below 60years, undertaken by a single surgeon, between 1992 and 2014 were explored. Cox regression models were fitted to investigate prognostic benefits of BITA. Specific comparisons were made with BITA subgroups who received LITA to LAD or RITA to LAD to establish long-term prognostic difference with the use of the RITA to LAD as compared to the LITA to LAD anastomosis. Comparisons were made with other BITA configurations to establish long-term difference in survival as a result of the actual targets bypassed with BITA grafts. Both groups had similar baseline patient characteristics. Following risk adjustment, the use of a second ITA conferred a significant 48% reduction in long-term mortality to BITA group [HR 0.52 (95%CI: 0.36-0.74) p < .001]. The use of the RITA to LAD, instead of LITA, resulted in no difference in the long-term prognostic benefit. The targets grafted with second ITA conferred a significant prognostic benefit for common configurations it was used in for bypass surgery. The use of BITA confers long term prognostic benefit to patients. Grafting RITA to LAD instead of more common LITA to LAD made no difference in long term prognosis when compared to CABG patients with single ITA. The use of a second ITA conduit in common configurations for CABG confers prognostic benefits irrespective of distal target grafted.