Prognostic Stratification Of Patients Research Articles

Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis.

Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA. Consecutive ATTR-CA patients (n=100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD SPECT/CT imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n=50; high DPD uptake: >5.4, n=50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r=0.366,p<0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r=0.316,p=0.002), LV diastolic function (E/e' average: r=0.304, p=0.013), NT-proBNP (r=0.332,p<0.001), troponin T (r=0.233,p=0.022), 6-minute walk distance (6MWD: r=-0.222,p=0.033) and National Amyloidosis Centre (NAC) stage (r=0.294,p=0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: p=0.012, RV-FW-LS: p=0.036), LV diastolic function (E/e' average: p=0.035), cardiac biomarkers (NT-proBNP: p=0.012, troponin T: p=0.044), exercise capacity (6MWD: p=0.035) and disease stage (NAC stage I: p=0.045, III: p=0.006), and experienced adverse outcomes compared to the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95%CI:1.439-5.737), p=0.003; DPD retention index: adjusted HR 1.221 (95%CI: 1.078-1.383), p=0.002]. In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA.

Grading carcinoembryonic antigen levels can enhance the effectiveness of prognostic stratification in patients with colorectal cancer: a single-centre retrospective study.

This study developed a refined carcinoembryonic antigen (CEA) grading system using CEA cut-off points of 5, 20 and 50 ng/mL and to explore the prognostic value of CEA grading in predicting the progression-free survival (PFS) and overall survival (OS) of colorectal cancer (CRC) patients. A retrospective cohort study. First Affiliated Hospital of Guangxi Medical University. 1107 CRC patients who received surgical treatment. Survival analysis was conducted using the Kaplan-Meier method and compared using the log-rank test. A Cox regression model with a 95% CI was used to evaluate the independent prognostic risk factors for CRC. Prognostic nomograms were constructed to predict the 1-5-year PFS/OS. Elevated serum CEA levels are often indicative of recurrence and death in CRC patients. Higher CEA levels were significantly associated with more aggressive tumour phenotypes. The CEA grading system was an independent predictor of prognosis in CRC patients and effectively stratified PFS (62.0% vs 51.2% vs 33.7% vs 20.2%, p<0.001) and OS (64.7% vs 54.4% vs 36.6% vs 22.5%, p<0.001) in CRC patients. As the CEA grade increased, the risk of poor prognosis gradually increased in a gradient manner, with an approximately 10% difference in risk grade between each CEA grade. The internal validation cohort further confirmed that CEA grade remains an effective prognostic factor for the survival of CRC patients. Prognostic nomograms, which integrate individual characteristics, tumour features and CEA grading, provide a more comprehensive prognostic evaluation for CRC patients. The CEA grading system is an independent predictor of prognosis for CRC patients and can effectively stratify PFS and OS.

Prognostic stratification of patients with pT4bN0M0 colorectal cancer following multivisceral resection: a multi-institutional case series analysis.

Colorectal cancer (CRC) patients with stage pT4b are a complex group as they show differences in tumor-infiltrated organs. Patients with the same stage often exhibit differences in prognosis after multivisceral resection (MVR). Thus far, some important prognostic factors have not been thoroughly investigated. Here, we identified the prognostic factors influencing CRC patients at the pT4bN0M0 stage to stratify the prognostic differences among patients. A retrospective analysis was conducted on patients diagnosed with locally advanced CRC and who underwent MVR at three medical institutions from January 2010 to December 2021. The prognostic factors affecting the survival of CRC patients at pT4bN0M0 stage were identified by multivariate Cox proportional hazard models. We then classified the prognosis into different grades on the basis of these independent prognostic factors. We enrolled 690 patients with locally advanced CRC who underwent MVR; of these, 172 patients with pT4bN0M0 were finally included. Patients with digestive system [overall survival (OS): hazard ratio (HR)=0.441; 95% confidence interval (CI)=0.217-0.900; P =0.024; disease-free survival (DFS): HR=0.416; 95% CI=0.218-0.796; P =0.008) or genitourinary system invasion (OS: HR=0.405; 95% CI=0.193-0.851; P =0.017; DFS: HR=0.505; 95% CI=0.267-0.954; P =0.035) exhibited significantly better OS and DFS as compared to those with gynecological system invasion, while the OS and DFS were similar between the digestive system and genitourinary system invasion groups (OS: HR=0.941; 95% CI=0.434-2.042; P =0.878; DFS: HR=1.211; 95% CI=0.611-2.403; P =0.583). Multivariate analysis showed that age (OS: HR=2.121; 95% CI=1.157-3.886; P =0.015; DFS: HR=1.869; 95% CI=1.116-3.131; P =0.017) and type of organs invaded by CRC (OS: HR=3.107; 95% CI=1.121-8.609; P =0.029; DFS: HR=2.827; 95% CI=1.142-6.997; P =0.025) were the independent prognostic factors that influenced the OS and DFS of CRC patients with pT4bN0M0 disease. The OS and DFS of patients showing invasion of the gynecological system group were significantly worse ( P =0.004 and P =0.003, respectively) than those of patients with invasion of the nongynecological system group. On the basis of the above-mentioned two independent prognostic factors, patients were assigned to high-risk, medium-risk, and low-risk groups. Subgroup analysis showed that the OS and DFS of the medium-risk and high-risk groups were significantly worse ( P =0.001 and P =0.001, respectively) than those of the low-risk group. Patients with pT4bN0M0 CRC show significant differences in their prognosis. The type of organs invaded by CRC is a valuable indicator for prognostic stratification of CRC patients with pT4bN0M0.

Multiparametric right ventricular assessment improves risk stratification in patients with new-onset acute heart failure.

Risk stratification of patients with new-onset acute heart failure (AHF) is important but remains challenging. In the present study, we evaluated the prognostic value of a new multiparameter right ventricular dysfunction (RVD) score. Patients (n=210) hospitalized due to new-onset AHF between 2015 and 2018 were retrospectively included. Mean age was 56±10years, 24% were female and median left ventricular ejection fraction was 28% (interquartile range 20; 34%). The RVD score, tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC) were determined at index hospitalization and after therapy titration. The 4-point RVD score included reduced TAPSE, right ventricular enlargement, moderate or severe tricuspid regurgitation and increased central venous pressure. The study endpoint was a composite of all-cause mortality, left ventricular assist device implantation, and heart transplantation. After 60months median follow-up time, 53 (25%) patients met the endpoint. At index hospitalization, there were no significant differences in any echocardiographic parameter between patients with and without the endpoint. After therapy titration, there were differences in TAPSE (16 vs. 19mm, P=0.001), FAC (33 vs. 40%, P<0.001) and the proportion of patients with RVD score ≥2 (36 vs. 4%, P<0.001). The presence of RVD despite therapy titration had different impact on survival depending on the parameter considered: the proportion of patients free from events after 1year was 87% in patients with TAPSE <17mm, 89% in patients with FAC <35% and 65% in patients with RVD score ≥2. In a multivariable analysis, RVD score ≥2 after therapy titration, but not TAPSE <17mm or FAC<35%, remained associated with a higher risk of the composite endpoint (hazard ratio 3.11, 95% confidence interval 1.44-6.74). A novel multiparametric RVD score might improve prognostic stratification in patients with new-onset AHF. RVD after therapy titration, but not at index hospitalization is associated with a higher risk of the composite endpoint.

Impact of examined lymph node count on survival outcomes in patients with stage T1-2N0M0 small cell lung cancer undergoing surgery: A retrospective cohort study.

To explore the relationship between the count of examined lymph nodes (ELNs) and survival outcomes in patients with stage T1-2N0M0 small cell lung cancer (SCLC) after surgical treatment. We analyzed data from patients with SCLC in the Surveillance, Epidemiology, and End Results database. The study focused on examining the correlation between the ELN count and both cancer-specific survival (CSS) and overall survival (OS). This relationship was investigated using restricted cubic spline curves within the framework of multivariable Cox regression models. The cutoff value for both CSS and OS was 7 ELN counts. Patients with ELN < 7 had a median CSS of 64 months, significantly lower than 123 months of patients with ELN ≥ 7 (P = .012). Multivariable Cox regression analysis indicated that ELN ≥ 7 was an independent prognostic factor for CSS (hazard ratio = 0.50, 95% confidence interval: 0.30-0.83; P = .007). Similarly, Patients with ELN < 7 had a median OS of 41 months for patients with ELN < 7, compared to 103 months for those with ELN ≥ 7 (P = .004). Multivariable Cox regression analysis confirmed that ELN ≥ 7 was an independent prognostic factor for OS (hazard ratio = 0.54, 95% confidence interval: 0.36-0.81; P = .003). ELN ≥ 7 is recommended as the threshold for evaluating the quality of postoperative lymph node examination and for prognostic stratification in patients with stage T1-2N0M0 SCLC undergoing surgery.

Revolutionizing T3-4N0-2M0 gastric cancer staging with an innovative pathologic N classification system

BackgroundThe current pathologic N (pN) classification exhibits limitations in the prognostic stratification of patients with pT3-4N0-2M0 gastric cancer (GC). Therefore, this study aimed to develop and validate a new lymph nodal staging method based on the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). MethodsData from 7883 patients with pT3-4N0-2M0 GC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and Zhejiang Cancer Provincial Hospital. Optimal cutoff values for ELNs and LNR were determined using X-tile software. Kaplan-Meier methods, Log-rank tests, and Cox regression analyses were employed in this study. Patients were categorized into 3 new pN stages: new pN0 (pN0 with ELNs of >16), new pN1 (pN0 with ELNs of ≤16 or pN1-2 with LNR of ≤0.15), and new pN2 (pN1-2 with LNR of >0.15). The prognostic predictive power of both current and new pN staging was evaluated using the Akaike information criterion (AIC), Bayesian information criterion, concordance index (C-index), and receiver operating characteristic curve. ResultsThe new pN classification exhibited excellent performance in Kaplan-Meier survival analysis. After adjusting for confounding factors, the new pN staging emerged as an independent prognostic indicator in patients with GC. In the SEER cohort, the new pN staging demonstrated enhanced prognostic prediction accuracy over the American Joint Committee on Cancer pN staging (AIC: 75578.85 vs 75755.06; C-index: 0.642 vs 0.630; P < .001). Similar findings were validated in the Chinese cohort. ConclusionThis study developed and validated an improved pN classification for patients with pT3-4N0-2M0 GC. Surgeons should consider ELNs and LNR when assessing postoperative prognosis in patients with GC.

PET/CT Imaging of Infectious Diseases: Overview of Novel Radiopharmaceuticals

Infectious diseases represent one of the most common causes of hospital admission worldwide. The diagnostic work-up requires a complex clinical approach, including laboratory data, CT and MRI, other imaging tools, and microbiologic cultures. PET/CT with 18F-FDG can support the clinical diagnosis, allowing visualization of increased glucose metabolism in activated macrophages and monocytes; this tracer presents limits in differentiating between aseptic inflammation and infection. Novel PET radiopharmaceuticals have been developed to overcome these limits; 11C/18F-labeled bacterial agents, several 68Ga-labeled molecules, and white blood cells labeled with 18F-FDG are emerging PET tracers under study, showing interesting preliminary results. The best choice among these tracers can be unclear. This overview aims to discuss the most common diagnostic applications of 18F-FDG PET/CT in infectious diseases and, as a counterpoint, to describe and debate the advantages and peculiarities of the latest PET radiopharmaceuticals in the field of infectious diseases, which will probably improve the diagnosis and prognostic stratification of patients with active infectious diseases.

Proposed novel grading system for stage I invasive lung adenocarcinoma and a comparison with the 2020 IASLC grading system.

Several studies have proposed grading systems for risk stratification of early-stage lung adenocarcinoma based on histological patterns. However, the reproducibility of these systems is poor in clinical practice, indicating the need to develop a new grading system which is easy to apply and has high accuracy in prognostic stratification of patients. Patients with stage I invasive nonmucinous lung adenocarcinoma were retrospectively collected from pathology archives between 2009 and 2016. The patients were divided into a training and validation set at a 6:4 ratio. Histological features associated with patient outcomes (overall survival [OS] and progression-free survival [PFS]) identified in the training set were used to construct a new grading system. The newly proposed system was validated using the validation set. Survival differences between subgroups were assessed using the log-rank test. The prognostic performance of the novel grading system was compared with two previously proposed systems using the concordance index. A total of 539 patients were included in this study. Using a multioutcome decision tree model, four pathological factors, including the presence of tumor spread through air space (STAS) and the percentage of lepidic, micropapillary and solid subtype components, were selected for the proposed grading system. Patients were accordingly classified into three groups: low, medium, and high risk. The high-risk group showed a 5-year OS of 52.4% compared to 89.9% and 97.5% in the medium and low-risk groups, respectively. The 5-year PFS of patients in the high-risk group was 38.1% compared to 61.7% and 90.9% in the medium and low-risk groups, respectively. Similar results were observed in the subgroup analysis. Additionally, our proposed grading system provided superior prognostic stratification compared to the other two systems with a higher concordance index. The newly proposed grading system based on four pathological factors (presence of STAS, and percentage of lepidic, micropapillary, and solid subtypes) exhibits high accuracy and good reproducibility in the prognostic stratification of stage I lung adenocarcinoma patients.

Proposal of New ypStage Grouping System for Esophageal Squamous Cell Carcinoma Patients who Underwent Neoadjuvant Chemoradiotherapy followed by Surgery.

To propose a new ypTNM grouping system to address these limitations and improve prognostic relevance. The current 8th edition of the American Joint Committee on Cancer (AJCC) ypStage system shows unsatisfactory prognostic relevance in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. The study cohort included 501 ESCC patients who received nCRT followed by esophagectomy at the Samsung Medical Center in Korea between 1994 and 2018 (development cohort) and 422 patients treated at Asan Medical Center (validation cohort). Recursive partitioning with a tree-structured regression model was used to develop and validate a new ypStage grouping system. In the new ypStage grouping system, ypStage I includes ypT0N0 only; ypStage II includes ypTis-T2N0 or ypT0-T2N1; ypStage III includes ypT3N0-N1; and ypStage IV includes ypT4N0-N1 or ypTanyN2-3. This system adequately addressed the limitations of the existing AJCC classification system, including overlapping and reversal of survival rates. Moreover, the discrimination ability of the new system was higher than that of the existing system [concordance-index (C-index): 61.9%] in the development (C-index: 66.6%) and validation (C-index: 66.0%) cohorts. NRIe was 0.17 [95% confidence interval (CI): 0.09-0.26, P-<0.001) and 0.18 (95% CI: 0.10-0.27, P-<0.001)] in the development and validation cohorts, respectively. The current study proposes a clear revised version of the 8th edition of the AJCC ypStage grouping system that exhibits superior prognostic stratification in patients with ESCC treated with nCRT followed by esophagectomy.

High-grade synovitis associates with clinical markers and response to therapy in chronic inflammatory arthritis: post hoc analysis of a synovial biomarkers prospective cohort study.

Inflammatory arthritis (IAs), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), are characterized by the presence of chronic synovitis. The Krenn's synovitis score (KSS), a simple tool detectable by haematoxylin/eosin staining of synovial biopsy samples, allows the discrimination between high-grade and low-grade synovitis. The aim of this study was to identify the clinical associations of KSS and to evaluate the relationship between high-grade synovitis and treatment response in IA patients. Clinical, laboratory and ultrasound data were retrieved from RA and PsA patients recruited in the prospective MATRIX cohort study. Inclusion criteria were age≥18 years, RA or PsA diagnosis, and presence of active disease with eligibility to start/modify therapy. Patients underwent ultrasound-guided synovial biopsy of one of the most involved joints before starting/modifying treatment according to treat-to-target strategy. The samples were analysed by an expert pathologist for KSS calculation. Univariable and multivariable logistic regression analyses were performed to evaluate the relationship between KSS and baseline variables. The association between KSS and treatment response at 24 weeks of follow-up was investigated in univariable logistic regression analysis. 53 patients, 34 RA and 19 PsA, completed 24 weeks of follow-up after synovial biopsy. Patients were either treatment naïve (N=6, 11%), csDMARDs-experienced (N=46, 87%) or b/tsDMARDs-experienced (N=20, 38%). Median KSS was 6.00 (Q1-Q3 4.00-7.00) in RA and 4.00 (3.00-6.00) in PsA (p=0.040), and inflammatory infiltrates score was significantly higher in RA than in PsA patients (median 3.00 vs 2.00, p=0.021). In multivariable analysis, synovial effusion in the biopsied joint (OR 9.26, 95%CI 2.12-53.91) and erythrocyte sedimentation rate (ESR) (OR 1.04, 95%CI 1.01-1.08) associated with high KSS. High-grade synovitis significantly associated with a higher probability of achieving DAS28 remission, ACR20/50 response, and Boolean2.0 remission, independently from diagnosis. Several markers of pro-inflammatory pathways associated with the presence of high-grade synovitis, and patients with higher KSS shared a higher probability of treatment targets achievement in the follow up. The integration of a simple and feasible tool like KSS in the clinical and prognostic stratification of patients with IA might help in intercepting patients with a disease more prone to respond to available treatment paradigms.

Identification of Optimal Parameters for Assessing Lymph Node Status of Patients with Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy.

This study aimed to compare the prognostic discrimination power of pretreatment pathologic N stage (prepN), lymph node tumor regression grade (LNTRG), and posttreatment pathologic N (ypN) category for esophageal squamous cell carcinoma (ESCC) patients who received neoadjuvant chemoradiotherapy (nCRT) plus surgery. The study reviewed 187 ESCC patients from two medical centers who underwent nCRT plus surgery. Pathologic LNTRG was defined by the proportion of viable tumor area within the tumor bed in lymph nodes (LNs). An average LNTRG then was calculated by averaging the tumor regression grade (TRG) score of all resected LNs. Lymph nodes containing regression changes or vital tumor cells were used for interpretation of the prepN stage, which reflects the estimated number of originally involved LNs. The ypN, prepN, and LNTRG categories had significant prognostic stratification power (p < 0.001, log-rank test). Multivariable cox regression showed that all three categories were independent prognostic factors of disease-free survival (DFS) (p < 0.05). The LNTRG category showed a better prognostic value for DFS prediction than the ypN and prepN categories (Akaike information criterion [AIC]: LNTRG [933.69], ypN [937.56], prepN [937.45]). Additionally, the superior predictive capacity of the LNTRG category was demonstrated by decision curve analysis. Similar results were discovered for patients with remaining diseased LNs. The three staging categories had prognostic relevance for DFS, with the LNTRG category seeming to have better prognostic indication power. Comprehensive consideration of the ypN status, prepN status, and LN regression may allow for better prognostic stratification of patients.

Accuracy of the GRACE Score for mortality prediction in myocardial infarction with nonobstructive coronary arteries (MINOCA)

Abstract Introduction Myocardial infarction with nonobstructive coronary arteries (MINOCA) patients account for 3.5 to 15% of all myocardial infarctions. The GRACE risk score is a well-validated tool for estimating short- and long-term risk in acute coronary syndrome, but the accuracy of the risk score for prognostic stratification in patients with MINOCA remains uncertain. Purpose We aimed to investigate whether the GRACE risk score can predict mortality in a real-world cohort of patients presenting with MINOCA. Methods We retrospectively analyzed patients admitted with MINOCA in a single center. Patients who were diagnosed with myocarditis and Takotsubo syndrome were excluded from the analysis. The GRACE risk score on admission was calculated. Patients were divided into a low-intermediate risk group (≤ 140 points, 71.5%) and a high-risk group (&amp;gt;140 points, 28.5%) according to their GRACE risk scores. Receiver operating characteristic (ROC) analysis was used to quantify the accuracy of the GRACE risk score to estimate both in-hospital and one-year mortality in MINOCA patients. Results Of a total of 3721 myocardial infarction patients, MINOCA was identified in 11.6% (n=430). 313 patients had complete data for the calculation of the GRACE on admission and were included in the analysis. Mean age was 65±12 years, and 49% (n=154) of patients were male. Mean GRACE score was 125±31 points. Patients in the high-risk group were older (74±9 vs. 61±11 years, p&amp;lt;0.001), had a higher incidence of in-hospital mortality (0.4% vs. 5.6%, p=0.008), and had a higher rate of one-year mortality (2.7% vs. 19.5%, p&amp;lt;0.001), compared with the low-intermediate risk group. There were no differences regarding sex and cardiovascular risk factors between the groups. In-hospital mortality was 1.9% and one-year mortality was 7.3%. ROC curve analysis showed that the GRACE risk score has a high value in predicting in-hospital mortality (AUC ROC 0.892; 95% CI 0.798–0.986; p=0.001), and one-year mortality (AUC ROC 0.826; 95% CI 0.739–0.0.914; p&amp;lt;0.001) in MINOCA patients. (Figure 1). The overall c-statistics were similar compared with estimates obtained from patients with myocardial infarction and significant coronary artery disease: in-hospital mortality (AUC ROC 0.0.849; 95% CI, 0.807–0.891; p&amp;lt;0.001); and one-year mortality (AUC ROC 0.776; 95% CI, 0.747–0.806; p&amp;lt;0.001). Conclusions In conclusion, the GRACE risk score provides potentially valuable prognostic information on in-hospital and one-year mortality when applied to MINOCA patients.Figure 1

Abstract 14575: Pupillary Reflex as an Independent Marker of Mortality in Decompensated Heart Failure. A Longitudinal and Prospective Study

Introduction: In heart failure (HF) compensatory mechanisms are triggered to maintain adequate cardiac output. Among them, hyperactivation of sympathetic nervous system (SNS) is one of the main ones and carries a worse prognosis. The pupillary reflex depends on the SNS. Aims: The aim of the study is to analyze whether changes in the pupillary reflex in HF are useful in the prognostic stratification of these patients. Hypothesis: Pupillary reflex may be a prognostic marker in patients with decompensated HF. Methods: We prospectively and consecutively included 107 patients admitted with decompensated HF. Quantitative pupillometry was performed with the NeuroOptics pupillometry during the first 24 hours after admission and prior to discharge. The basal maximum pupillary diameter (BMPD) before contraction, was measured. Results: Of the 107 patients, 51% were women and 49% men, mean age was 79 +/- 10 years, 77% had hypertension, and 34% Diabetes.6 patients died during admission, 11 died in the first month after discharge and 4 patients were readmitted in the first month.Of the patients who died, all had on admission BMPD &gt; 3.8 mm. No patient with a BMPD &lt; 3.7 mm died. The area under curve ROC for predicting the combined endpoint of 1- month mortality and admissions for HF using BMPD was 0.823. The BMPD presented a weak correlation with heart rate and ejection fraction. It did not correlate with age, gender, BNP, mean E/e, left atrial volume indexed, creatinine, hematocrit, sodium. Conclusions: Patients with decompensated HF presented at admission a higher BMPD. This supports the hypothesis that decompensated HF present a hyperactivation of the SNS that promotes mydriasis. BMPD is provides a good independent predictor marker of in-hospital and 1-month mortality in patients admitted with HF. Pupillometry may be a new, non-invasive and simple tool that helps in the prognostic stratification of acute HF patients.

Covid score – the contribution in prognostic stratification of patients with COVID-19

Covid score – the contribution in prognostic stratification of patients with COVID-19

Prognostic value of cardiopulmonary exercise testing repetition during follow-up of clinically stable patients with severe dilated cardiomyopathy. A preliminary study

BackgroundCardiopulmonary exercise testing (CPET) is a recognized tool for prognostic stratification in patients with dilated cardiomyopathy (DCM). Given the lack of data currently available, the aim of this study was to test the prognostic value of repeating CPET during the follow-up of patients with DCM. MethodsThis multicenter, retrospective study, analyzed DCM patients who consecutively performed two echocardiographies and CPETs during clinical stability. The study end-point was a composite of death from all causes, heart transplantation, left ventricular assist device implantation, life-threatening ventricular arrhythmias or hospitalization for heart failure. Results216 DCM patients were enrolled (52 years, 78% male, NYHA I-II 82%, LVEF 32%, 94% on ACE inhibitors/ARNI, 95% on beta-blockers). The interval between CPETs was 15 months. During a median follow-up of 38 months from the second CPET, 102 (47%) patients experienced the study end-point. Among them, there was stability of echocardiographic values but a significant worsening of functional capacity.Among the 173 patients (80%) who did not show echocardiographic left ventricular reverse remodeling (LVRR), the 1-year prevalence of the study-end point was higher in patients who worsened vs patients who maintained stable their functional capacity at CPET (38 vs. 15% respectively, p-value: 0.001).These results were consistent also when excluding life-threatening ventricular arrhythmias from the composite end-point. ConclusionIn clinically stable DCM patients with important depression of LVEF, the repetition of combined echocardiography and CPET might be recommended. When LVRR fails, 1-year repetition of CPET could identify higher-risk patients.

The associations between tricarboxylic acid cycle metabolites, and risk of major adverse cardiovascular events in acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease and acute coronary syndrome (ACS) are one of the main causes of morbi-mortality caring a high health cost due to its consequences. Prognostic stratification in patients admitted with an acute coronary syndrome (ACS) is necessary to providing efficient follow-up and guiding intensive treatment to those at high risk of adverse cardiovascular events. Is crucial to identifying new molecular pathways to predict those patients with worst prognosis and find new molecular targets. Purpouse The aim of the study is to investigate the relation between TCA cycle disturbance and cardiovascular diseases. Methods In this prospective cohort study, we included 309 patients with ACS. During a mean follow-up of 6.7 years, 131 patients developed major adverse cardiovascular events (MACE) (myocardial infarction, hospitalization for heart failure, and all-cause mortality). Plasma concentrations of TCA cycle metabolites were profiled by liquid chromatography tandem mass spectrometry. Hazard ratios were estimated with multivariable Cox regression models. Results After adjustment for traditional cardiovascular risk factors and medications, participants in the highest tertile vs. the lowest tertile of baseline Isocitrate concentrations had a higher risk of MACE [(HR: 1.25; 95% CI: 1.03, 1.5) However, these associations were no longer significant, after additional adjustment for eGFR. eGFR mediated the associations of Isocitrate (75 %) No significant associations were found for other TCA metabolites. Conclusions High plasma TCA metabolites concentrations are related to the risk of developing MACE during the follow-up and this relationship is substantially mediated by renal function. Understanding the potential interplay of TCA metabolite’s renal function, and incident MACE, may contribute to novel prevention and treatment efforts in ACS.

P404 MYOCARDIAL WORK EVALUATION IN PATIENTS WITH SEVERE AORTIC STENOSIS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT

Abstract Background myocardial work (MW) is a novel echocardiographic technique that enables the study of left ventricular performance. It overcomes speckle tracking echocardiography (STE) limitations, dependent on afterload, which is increased in patients with severe aortic stenosis (AS). Aims: To evaluate myocardial performance indexes obtained with MW in patients with AS and indication to percutaneous aortic valve replacement (TAVR) before and after the procedure. Methods patients with severe AS and preserved left ventricular systolic function (LVEF) and indication to TAVR underwent complete echocardiographic evaluation the day before and within two days after the procedure. MW indices were calculated considering noninvasive systolic blood pressure (SBP) and corrected for the mean transvalvular aortic gradient. Results 39 patients (78±6 years, 61.5% women) were enrolled, they presented at baseline preserved LVEF (59.4±8.2%) and reduced global longitudinal strain (GLS) (–16.8±3.3%). Corrected global work index (cGWI) and corrected global constructive work (cGCW) appeared elevated before the procedure, and were significantly reduced within 2 days after TAVR (cGWI –2460.5±839.7 mmHg% vs 1844.4±521.6 mmHg%, p&amp;lt;0.01; cGCW 3061.3 ± 796.0 vs 2277.4 ± 536.5mmHg%, p&amp;lt;0.01). Adjusted global wasted work (cGWW) and adjusted global work efficiency (cGWE) did not change significantly after TAVR (cGWW 262.6±151.8 vs 244.2±129.2 mmHg%, p=0.236; cGWE 90.1±4.5 vs 88.5±5.2%, p=0.079) in the overall population. In the subgroup of patients who had not developed new atrioventricular or intraventricular conduction abnormalities, cGWW also significantly decreased following TAVR (275±152.6 vs 216.3 ± 99.7 mmHg%, p=0.018), with no change in cGWE (89.7±4.8 vs 89.3±5.8%, p=0.838). Conclusions The reduction in cGWI and cGWC values and thus myocardial oxygen consumption in the immediate post–TAVR is attributable to the reduction in afterload. Left ventricular function abnormalities do not totally regress after the procedure, although the lack of reduction in cGWW could be partly due to the development of atrioventricular or intraventricular conduction defects. Further studies are desirable to define a role of MW in prognostic stratification of patients with severe AS.

Histone acetylation gene-based biomarkers as novel markers of the immune microenvironment in glioblastoma.

Glioblastoma (GBM) is a primary malignant tumour with high intracranial morbidity, high malignancy and poor prognosis. Abnormal changes in histone acetylation are closely related to the occurrence and development of cancer. However, there is still a lack of systematic research on histone acetylation in GBM. Whole-transcriptome sequencing data and clinical data of GBM patients were obtained through the TCGA database. Single-cell RNA-sequencing (scRNA-seq) data from GBM patients were obtained from GSE146711 in the Gene Expression Omnibus database. Cell descending fractionation was first performed for scRNA-seq on GBM. The CellChat and PROGENy scores explore the impact of the histone acetylation pathway in GBM on intercellular chat and tumour pathways. The AddModuleScore function evaluates the enrichment score of histone acetylation in cells and divides them into high-histone acetylation and low-histone acetylation groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differential genes between different histone acetylation states, and the biological processes and pathways that may be affected by histone acetylation were evaluated. Based on this, a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) analysis, and survival analysis was performed to evaluate its prognostic performance. Finally, we also analysed the main effects of the constructed histone acetylation-related model on GBM immune infiltration by multiple methods, and analysed the main mutation data of its different subgroups. GBM samples mainly include seven large cell populations: oligodendrocyte precursor cells (OPCs), myeloid, neoplastic, oligodendrocytes, astrocytes, vascular and neurons. Cellchat and ProgenY scores revealed that in GBM tumours, histone acetylation interacts closely with multiple immune cells and tumour pathways. GO and KEGG analyses revealed the main impact proteins and pathway correlates of histone acetylation. Five histone acetylation genes were screened using LASSO analysis and a prognostic model was constructed. The results revealed that prognostic models were significant in the prognostic stratification of patients in both the training and validation groups of GBM patients. Immune infiltration analysis revealed that the mechanism of histone acetylation in GBM may be related to the immune infiltration of multiple effector immune cells. Our histone acetylation-based biomarkers are closely associated with immune microenvironmental infiltration and functional mutations in multiple tumour pathways in GBM. This suggests that histone acetylation may reveal microscopic alterations in the tumour microenvironment, and may provide potential evidence and a research basis for the development of novel therapeutic targets for GBM. On this basis, a novel perspective on the spatial biology and immunological understanding of GBM is provided.

Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma

Cholangiocarcinoma (CCA), heterogeneous biliary tumours with dismal prognosis, lacks accurate early diagnostic methods especially important for individuals at high-risk (i.e. those with primary sclerosing cholangitis [PSC]). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). EVs from patients with isolated PSC (n= 45), concomitant PSC-CCA (n= 44), PSC who developed CCA during follow-up (PSC to CCA; n= 25), CCAs from non-PSC aetiology (n= 56), and hepatocellular carcinoma (n= 34) and healthy individuals (n= 56) were characterised by mass spectrometry. Diagnostic biomarkers for PSC-CCA, non-PSC CCA, or CCAs regardless of aetiology (Pan-CCAs) were defined and validated by ELISA. Their expression was evaluated in CCA tumours at a single-cell level. Prognostic EV biomarkers for CCA were investigated. High-throughput proteomics of EVs identified diagnostic biomarkers for PSC-CCA, non-PSC CCA, or Pan-CCA, and for the differential diagnosis of intrahepatic CCA and hepatocellular carcinoma, which were cross-validated by ELISA using total serum. Machine learning-based algorithms disclosed CRP/FIBRINOGEN/FRIL for the diagnosis of PSC-CCA (local disease [LD]) vs. isolated PSC (AUC= 0.947; odds ratio [OR]=36.9) and, combined with carbohydrate antigen 19-9, overpowers carbohydrate antigen 19-9 alone. CRP/PIGR/VWF allowed the diagnosis of LD non-PSC CCAs vs. healthy individuals (AUC= 0.992; OR= 387.5). It is noteworthy that CRP/FRIL accurately diagnosed LD Pan-CCA (AUC= 0.941; OR= 89.4). Levels of CRP/FIBRINOGEN/FRIL/PIGR showed predictive capacity for CCA development in PSC before clinical evidence of malignancy. Multi-organ transcriptomic analysis revealed that serum EV biomarkers were mostly expressed in hepatobiliary tissues, and single-cell RNA sequencing and immunofluorescence analysis of CCA tumours showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EV prognostic biomarkers, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively and positively with patients' survival, respectively. Serum EVs contain protein biomarkers for the prediction, early diagnosis, and prognostication of CCA that are detectable using total serum, representing a tumour cell-derived liquid biopsy tool for personalised medicine. The accuracy of current imaging tests and circulating tumour biomarkers for cholangiocarcinoma (CCA) diagnosis is far from satisfactory. Most CCAs are considered sporadic, although up to 20% of patients with primary sclerosing cholangitis (PSC) develop CCA during their lifetime, constituting a major cause of PSC-related death. This international study has proposed protein-based and aetiology-related logistic models with predictive, diagnostic, or prognostic capacities by combining two to four circulating protein biomarkers, moving a step forward into personalised medicine. These novel liquid biopsy tools may allow the (i) easy and non-invasive diagnosis of sporadic CCAs, (ii) identification of patients with PSC with higher risk for CCA development, (iii) establishment of cost-effective surveillance programmes for the early detection of CCA in high-risk populations (e.g. PSC), and (iv) prognostic stratification of patients with CCA, which, altogether, may increase the number of cases eligible for potentially curative options or to receive more successful treatments, decreasing CCA-related mortality.

943 THE RIGHT VENTRICULAR-ARTERIAL COUPLING AS AN INDICATOR OF PROGNOSIS IN PATIENTS WITH FUNCTIONAL MITRAL REGURGITATION UNDERGOING TRANSCATHETER “EDGE-TO-EDGE“ VALVE REPAIR

Abstract Aims Patients affected by severe functional Mitral Regurgitation (MR) complaining symptoms despite optimal medical therapy should undergo intervention. When the surgery, the gold standard, is not indicated due to high surgical risk, the transcatheter edge-to-edge repair (TEER) should be considered, if feasible. In patients undergoing TEER, the clinical outcome is not always optimal and strongly correlates to the patient's clinical conditions, so a correct selection of the patients is essential. In this regard, some studies have evaluated the RV-PA coupling as an important predictor of outcome in patients with Heart Failure (HF). In clinical practice, RV-pulmonary artery (PA) coupling could be estimated in a non-invasive way through the relationship between TAPSE (systolic excursion of the annular plane of the tricuspid valve) /PAPs (systolic pressure of the pulmonary artery) ratio that gives information about the state of contractility and adaptability to the load of the RV. In this study, we sought to evaluate how the TAPSE /PAPs ratio at baseline may improve prognostic stratification in patients undergoing TEER with the MitraClip system. Methods and Results Data from 236 patients with symptomatic, moderate to severe functional MR, subjected to implantation of MitraClip between March 2012 and June 2021, were obtained from the University's MITRA-CTV, multicenter observational register comprising data from the Magna Graecia University of Catanzaro (Italy), the University of Turin (Italy) and the University of Vigo (Spain). The median follow-up was 686 days (IQR 393-1131 days), with a 1-year follow-up in 224 of 236 (95%) patients. We divided the population into two groups based on the median value of the ratio TAPSE / PAPs ≤ 0.35 and TAPSE / PAPs&amp;gt; 0.35. The primary endpoint of this study includes Re-hospitalization for HF and Death from all causes at one-year follow-up. At Cox regression analysis, Hospital stay&amp;gt; 10 days (HR 1.67, 95% CI [1.03-2.77], p = 0.039) and the TAPSE / PAPs ratio ≤ 0.35 (HR1.58, 95% CI [1, 01-2.48], p = 0.0488) independently increased the risk of the primary endpoint at long-term follow-up. At Kaplan Meier analysis, a TAPSE / PAPs ratio of ≤ 0.35 was related to an increased incidence of the primary endpoint of Rehospitalization for HF and Death (HR 1.54, 95% CI [ 1-2.41], p = 0.0464). Conclusion In our study, the right ventricular-arterial coupling, estimated through TAPSE/PAPs Ratio, was identified as a predictor of outcome in patients with severe functional MR undergoing TEER.