Prognostic Predictor Research Articles

Association Between Changes in Skeletal Muscle Quality and Prognosis in Postoperative Patients with Early Gastric Cancer.

Identifying accurate prognostic factors is crucial for postoperative management of early gastric cancer (EGC) patients. Skeletal muscle quality (SMQ), defined by muscle density on computed tomography (CT) images, has been proposed as a novel prognostic factor. This study compared the prognostic significance of SMQ changes with the well-established factor of body weight (BW) loss in the postoperative EGC setting. This single-center retrospective study included 297 postoperative EGC patients (median age 69 years, 68.4% male) who had preoperative and 1-year-postoperative gastrectomy CT images. SMQ was defined as the modified intramuscular adipose tissue content (mIMAC = skeletal muscle density-subcutaneous fat density on CT images) and the change as ΔmIMAC. Log-rank test, Kaplan-Meier survival, and Cox proportional hazards regression analyses were used to assess the associations between prognosis and either ΔmIMAC or BW change (ΔBW). Prognosis prediction by ΔmIMAC and ΔBW was compared by using the area under the curve (AUC) of the receiver operating characteristic curve. ΔmIMAC was significantly associated with prognosis (log-rank test; P = 0.037), but ΔBW was not (P = 0.243). Prognosis was significantly poorer in the severely decreased mIMAC group than in the preserved group (multivariate Cox proportional hazards regression analysis; P = 0.030) but was unaffected by BW changes (P = 0.697). The AUC indicated a higher prognostic value for ΔmIMAC than ΔBW (ΔmIMAC: AUC = 0.697, ΔBW: AUC = 0.542). One-year post-gastrectomy SMQ changes may be better prognostic EGC predictors than BW changes.

Assessing Artificial Intelligence in Oral Cancer Diagnosis: A Systematic Review

Background: With the use of machine learning algorithms, artificial intelligence (AI) has become a viable diagnostic and treatment tool for oral cancer. AI can assess a variety of information, including histopathology slides and intraoral pictures. Aim: The purpose of this systematic review is to evaluate the efficacy and accuracy of AI technology in the detection and diagnosis of oral cancer between 2020 and 2024. Methodology: With an emphasis on AI applications in oral cancer diagnostics, a thorough search approach was used to find pertinent publications published between 2020 and 2024. Using particular keywords associated with AI, oral cancer, and diagnostic imaging, databases such as PubMed, Scopus, and Web of Science were searched. Among the selection criteria were actual English-language research papers that assessed the effectiveness of AI models in diagnosing oral cancer. Three impartial reviewers extracted data, evaluated quality, and compiled the findings using a narrative synthesis technique. Results: Twelve papers that demonstrated a range of AI applications in the diagnosis of oral cancer satisfied the inclusion criteria. This study showed encouraging results in lesion identification and prognostic prediction using machine learning and deep learning algorithms to evaluate oral pictures and histopathology slides. The results demonstrated how AI-driven technologies might enhance diagnostic precision and enable early intervention in cases of oral cancer. Conclusion: Unprecedented prospects to transform oral cancer diagnosis and detection are provided by artificial intelligence. More resilient AI systems in oral oncology can be achieved by joint research and innovation efforts, even in the face of constraints like data set variability and regulatory concerns.

Clinical significance of 12-lead electrocardiogram QRS scores on admission in ST-segment elevation myocardial infarction

Abstract Background A QRS scoring system by 12-lead electrocardiography (ECG) is a quick and simple method to evaluate degree and extension of myocardial infarction. Previous studies have shown that high QRS scores (≥5) at hospitalization (before reperfusion) related to impaired myocardial reperfusion during percutaneous coronary intervention (PCI) and subsequent poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI) (Figure 1). However, the pathogenesis and associated factors with high QRS scores remain poorly defined. Therefore, this study aimed to explore clinical and lesion characteristics associated with QRS scores at hospitalization in patients with STEMI. Methods This retrospective observational study enrolled 138 broad anterior-wall STEMI patients who underwent PCI in the proximal left anterior descending artery and achieved reperfusion within 3 hours of onset. Patients were divided by QRS scores at hospitalization into low (<5: n=97) and high (≥5: n=41) QRS-scores, and clinical and lesion characteristics were compared between the 2 groups. Lesion characteristics were evaluated by intravascular ultrasound (IVUS). Results Despite early phase of STEMI, QRS scores at hospitalization varied (3 [2-5] points). Clinical characteristics, including onset-to-door time (66 [41-101] min vs. 55 [42-76] min) and onset-to-reperfusion time (112 [88-145] min vs. 106 [81-120] min), were comparable between patients with low and high QRS-scores. In contrast, significantly higher percentages of lipid plaques, plaque rupture and large thrombus were seen at the culprit lesion sites in patients with high versus low QRS scores (Figure 2). As a result, patients with high QRS scores had higher incidence of no-reflow phenomenon during PCI (36.6% vs. 12.6%, p<0.05) and larger infarct size assessed by peak CK values (5333 [3307-7443] IU/l vs. 1941 [759-3559], p<0.05) compared with those with low QRS-scores. Conclusions High QRS scores at hospitalization were associated with vulnerable lesion characteristics, as well as impaired coronary reperfusion and large infarct size. Although the exact mechanisms of the associations require future studies, QRS scores may help risk stratification before reperfusion and prognostic prediction after reperfusion.Figure 1.Figure 2.

Association between clinical ischemic risk and thrombogenicity phenotype and their prognostic prediction in patients undergoing percutaneous coronary intervention

Abstract Introduction The CHADS-P2A2RC score has been developed to provide better prognostic precision and improved selection of at-risk patients with coronary artery disease (CAD). The linkage of this clinical ischemic risk with thrombogenicity and their prognostic implication remain still unknown. Purpose We investigated the values of thrombogenicity indices according to the CHADS-P2A2RC score and their combined prognostic prediction in CAD patients undergoing percutaneous coronary intervention (PCI). Methods In PCI-treated patients (PCI) (n=2,705), clinical ischemic risk was classified with CHADS-P2A2RC score ("high risk": ≥ 4) and thrombogenicity indices were assessed using thromboelastography (TEG). Major adverse cardiovascular events (MACEs: a composite of all-cause death, myocardial infarction, or stroke) and major bleeding were evaluated were monitored for up to 3 years. Results Compared with "low/moderate-risk group" (67.7%), "high-risk group" (32.3%) had higher platelet-fibrin clot strength (PFCS: 67.3±7.9 vs. 65.2±7.2 mm; P < 0.001) and lower fibrinolytic activity (clot lysis at 30 min [LY30]: 0.9±2.1% vs. 1.1±2.4%, P < 0.001]. The "high-risk group" showed higher rates of "high PFCS phenotype (≥ 68 mm)" (35.3% vs. 49.7%; P <0.001), MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; P = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; P = 0.013) than the "low/moderate-risk group", respectively. Among the "low/moderate-risk group", "high MA phenotype" independently predicted MACE (HRadjusted: 1.51; 95% CI: 1.00-2.27; P = 0.048) and all-cause mortality (HRadjusted: 1.90; 95% CI: 1.06-3.4; P = 0.031). Likewise, this phenotype increased the risks of MACE (HRadjusted: 1.47; 95% CI: 1.01-2.13; p = 0.045) and all-cause mortality (HRadjusted: 1.87; 95% CI: 1.14-3.07; p = 0.013) in the "high-risk group" (Table 1 and Figure 1). Prognostic impact of "high MA phenotype" on major bleeding was not significantly different across the risk-group (HRadjusted: 1.02; 95% CI: 0.39-2.72; P = 0.963 in the "low/moderate-risk group" and HRadjusted: 1.08; 95% CI: 0.50-2.34; P = 0.884 in the "high-risk group", respectively). Conclusion In PCI-treated patients, CHADS-P2A2RC score was significantly associated with a worse clinical outcome and more thrombogenic profile. Regardless of the ischemic-risk group, the level of clot-strength had an addictive effect on predicting the risk of ischemic event, indicating assessment of thrombogenicity indices using TEG may enhance post-PCI risk stratification for personalized antithrombotic therapy.

Myocardial parametric mapping in patients with suspected acute myocarditis: a prognosis study

Abstract Background T1 mapping and T2 mapping have become essential components of the 2018 Lake Louise criteria and obtained excellent results in diagnosing myocarditis. However, their prognostic value in acute myocarditis has not yet been well recognized or established. Purpose Our study aims to investigate the prognostic value of T1 mapping, T2 mapping, and extracellular volume fraction (ECV) in a large cohort of patients with suspected acute myocarditis. Materials Patients meeting the recommended clinical criteria for suspected acute myocarditis were consecutively enrolled. The primary endpoint is the composite of cardiac death, heart failure hospitalization, heart transplantation, sustained ventricular arrhythmia, and recurrent myocarditis, defined as major adverse cardiovascular events (MACE). All patients underwent CMR at 3.0 T scanner using a standardized, routine imaging protocol, and the three short-axis view slices (basal, mid-ventricular, and apical) were divided into 16 segments according to the American Heart Association 17-segment model (apex excluded). We also averaged the native T1 values, ECV, and T2 values of all 16 segments to get global T1 and ECV fraction values, respectively. Statistically significant parameters from univariate Cox analyses were put into multivariate Cox analysis. Results A total of 235 patients (150 men; 32±13 years) were enrolled in this study. During a mean follow-up of 43.0±3.6 months, MACE occurred in 37 patients (15.7%) and was univariably associated with heart failure presentation, left ventricular ejection fraction, left ventricular end-systolic volume index, left ventricular end-diastolic volume index, native T1 and ECV. Patients with MACE showed higher global native T1, ECV, and T2 values (1348±59 vs 1266±51, p=<0.001; 40.0±8.7 vs 32.8±5.9, p<0.001; 63.4±12.1 vs. 55.5±9.1, p=0.011), and were more likely to have tissue changes in the interventricular septum and anterior wall (Figure 1). In a series of nesting multivariable Cox regression models, the addition of native T1 (per 10-ms increase: HR, 1.128; 95% CI: 1.043, 1.220; p = 0.003; Harrell’s C-index = 0.833) or ECV (per 5% increase: HR, 1.382; 95% CI: 1.060, 1.802; p = 0.017; Harrell’s C-index = 0.847) improved prognostication compared with the model based on clinical variables, left ventricular ejection fraction, and septal late gadolinium enhancement (Harrell’s C-index = 0.762) (Figure 2). T2 in multivariate Cox regression analysis didn’t show predictive value, but his inclusion increased the C-index of the model to 0.814. Conclusions Myocardial parametric mapping not only holds substantial diagnostic value but also plays a critical role in the prognostic assessment and risk prediction of myocarditis. Their utilization in these contexts enhances the accuracy and effectiveness of clinical evaluations and decision-making processes.

Quality of muscle in the thigh predicts the prognosis in patients with non-ischemic cardiomyopathy

Abstract Background Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia has garnered scientific attention. Furthermore, the importance of not only muscle mass but also quality of muscle has been pointed out. And a sarcopenia diagnosis is confirmed by the presence of low quality of muscle. However, there is a lack of consensus on the implications of ectopic fat as a quality of muscle for the prognosis in patients with non-ischemic cardiomyopathy. Purpose We investigated whether intramuscular fat (IMF) in the thigh affects the prognosis in patients with non-ischemic cardiomyopathy. Methods We recruited 250 patients who were diagnosed with non-ischemic cardiomyopathy by cardiac catheterization and echocardiographic date between September 2017 and November 2022. Finally, 223 patients enrolled in this prospective study conducted at a single center. Functional status was evaluated by using cardiopulmonary exercise test at baseline. All patients were measured quantity of the percentage of IMF (%IMF) in the thigh using computed tomography scan. Demographic, laboratory and echocardiographic date were collected from the patients’ medical records. Patients were followed up for up to 3 years. Clinical endpoints were cardiovascular death or unexpected rehospitalization because of cardiac events. Results During the follow-up 58 patients had cardiac events. The %IMF was significantly higher in the group with adverse events than without (4.49 ± 4.21 and 3.06 ± 2.39%, respectively; p = 0.001). Spearman correlation coefficient analysis showed a modest correlation between %IMF and exercise tolerance such as anaerobic threshold (Spearman r = -0.367; p < 0.001) and peak oxygen uptake (Spearman r = -0.382; p < 0.001). Patients were divided into 2 groups according to the median values of %IMF. Kaplan-Meier analysis demonstrated that events were significantly higher in the high %IMF group (log-rank p = 0.008). Furthermore, subgroup with left ventricular ejection fraction ≦ 40% or BMI ≧ 22 had a significantly greater frequency of adverse events in the high %IMF group. However, there was no significant difference in %IMF between the groups when divided into two groups at the mean age of this study. Multivariate Cox regression analysis adjusted for left ventricular ejection fraction, estimated glomerular filtration rate, hemoglobin and body mass index found %IMF as an independent factor of adverse events (hazard ratio 1.088; 95% confidential interval 1.024-1.156; p = 0.007). Conclusions In patients with non-ischemic cardiomyopathy, quality of muscle represented by %IMF in the thigh is an independent factor for predicting adverse cardiac events.

Transferrin saturation is a superior prognostic biomarker for iron deficiency after acute decompensated heart failure: a retrospective clinical real-world cohort study

Abstract Background Iron deficiency (ID) is the most common extracardiac comorbidity in heart failure (HF) and associated with worse outcomes. While a uniform definition of ID in HF remains lacking, several biomarkers for ID, including ferritin and transferrin saturation (TSAT), are used in both clinical trials and clinical practice. However, which biomarker is a superior prognostic predictor for ID in HF remains unsettled. In addition, real-world clinical data on ID screening and intravenous (IV) iron treatment is largely missing. Purpose To determine which biomarker is a superior prognostic predictor for the composite endpoint of HF rehospitalisation (HHF) and all-cause mortality in a real-world cohort of patients with HF and coexisting ID, and to investigate frequency and predictors of ID screening and IV iron treatment. Methods In this retrospective cohort study, all patients aged 18-85 years hospitalised at a tertiary university hospital with new onset HF with reduced ejection fraction (HFrEF) in 2016-2020 were consecutively included from medical records by ICD-10 code I50.0-I50.9 and followed until 31 December 2021. Patient characteristics, comorbidities, medications, laboratory results and data on follow-up, including if ID was tested for, IV iron administration, HHF and all-cause mortality was collected. First available iron status after admission for index hospitalisation was used. Predictors for ID screening and IV iron use were identified with univariate logistic regression. The association between ID markers and the composite endpoint was analysed with Cox regression adjusted for age, sex, baseline anemia, estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and N-terminal pro-B type natriuretic peptide (NT-proBNP) below median value with median ferritin and TSAT values set as references respectively. Results In all, 753 patients were included (66.5 ± 12.7 years, 508 (67.5%) men, ejection fraction 29.5 ± 6.9% and mean NT-proBNP 6241 ± 7183 ng/L). Of these, 484 (64.3%) were screened for ID and 235 (48.6%) fulfilled criteria for ID. Of these, 94 (40.0%) received IV iron. Of screened patients, 28.6% had ID with anemia and 20.8% ID without anemia (Table 1). Factors associated with screening for ID were follow-up at hospital, anemia, eGFR <30 mL/min/1.73 m2 and ischemic heart disease, and for IV iron additionally chronic kidney disease and peripheral artery disease. Median ferritin was 140 µg/L and TSAT 0.2. Both ferritin and TSAT displayed an inversely linear association with outcomes, while TSAT <0.2 showed a stronger association with increased risk of HHF and all-cause mortality compared to median values (Figure 1-2). Conclusions In a real-world clinical setting, TSAT was a superior prognostic biomarker for worse outcomes compared to ferritin in patients hospitalised for acute HF. While both ID screening and IV iron use remained greatly underutilised in clinical practice, identification of a reliable biomarker for ID is critical.

The activation of cardiac sympathetic nervous system in the non-culprit lesion is a strong prognostic predictor in patients with acute myocardial infarction

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). However, it remains to be determined whether regional assessment of cardiac sympathetic nerve activity (CSNA) in the culprit and non-culprit lesion of the cardiac MIBG SPECT imaging could have prognostic value in patients with AMI. Purpose The purpose of this study is to investigate the prognostic impact of regional CSNA in patients with AMI. Methods We prospectively enrolled 122 patients with AMI who visited our emergency department and underwent primary percutaneous coronary intervention. The late heart-to-mediastinum ratio (HMR) and washout rate (WR) was calculated to assess CSNA in the whole heart from planar images of in the cardiac MIBG imaging. The MIBG SPECT image parameters were calculated for each coronary artery, and the average WR in the culprit and non-culprit lesion were evaluated to assess the regional status of CSNA in patients with AMI. Abnormal WR in planar image was defined as 34% or more, as previously reported. The cut-off value of late HMR in planar image, WR in the culprit and non-culprit lesions were determined by ROC analysis. The primary endpoint was major adverse cardiac event (MACE) including all cause death, myocardial infarction, hospitalization for heart failure and target lesion revascularization. Results During a mean follow-up period of 3.1±1.8 years, 25 of 122 patients underwent MACE. The late HMR (p=0.004), WR in planar image (p=0.002), WR in the culprit lesion (p=0.023), and WR in the non-culprit lesion (p<0.001) were significantly associated with MACE at univariate Cox proportional hazard analysis. The increased WR in the non-culprit lesion (defined as 28.3% or more: AUC 0.697 [0.576-0.817]) was significantly independently associated with MACE (hazard ratio: 4.36 [1.45-13.11], p=0.009) even adjusted by late HMR, WR in planar image or WR in the culprit lesion, while decreased HMR, abnormal WR in planar image and increased WR in the culprit lesion showed no significant association with MACE in the multivariate model with WR in the non-culprit lesion. Kaplan-Meier analysis revealed that patients with increased WR in the non-culprit lesion had significantly higher risk for MACE than those without increased WR (45% vs 11% p<0.001). Conclusion(s) The activation of cardiac sympathetic nervous system in the non-culprit lesion is particularly associated with poor prognosis in patients with acute myocardial infarction.MACE risk by WR in non-culprit lesion

Prognosis in patients with residual pulmonary hypertension after transcatheter edge-to-edge repair for secondary mitral regurgitation

Abstract Background Pulmonary hypertension (PH) is an independent prognostic predictor in patients with heart failure (HF). Recently, transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) has been reported to reduce HF hospitalizations and mortality. Elevated pulmonary artery pressure (PAP) before TEER is associated with a poor prognosis; however, the impact of residual PH after TEER on clinical events has not been investigated. Purpose The purpose of this study is to clarify whether residual PH influences outcomes in patients with HF treated by TEER for secondary MR. Methods We included 63 patients who underwent TEER for severe secondary MR and post-procedural right heart catheterization in our institute from January 2016 to August 2023. Mean PAP after TEER was categorized as increased (>20mmHg) versus not increased (≤20mmHg), and we investigated the clinical outcomes between the two groups. The primary endpoint is a composite outcome of all-cause mortality and HF hospitalization. Results Among 63 patients, the average age was 78 years, and 60.3% were male. All patients had Secondary MR, and 52 patients (82.6%) had ventricular Secondary MR—right heart catheterization after TEER revealed a mean PAP of 21.6±7.7 mmHg, pulmonary vascular resistance (PVR) of 2.7±1.4 wood unit (WU), and pulmonary artery wedge pressure (PAWP) of 12.2±5.9 mmHg. Patients with residual PH had higher composite outcome rates of death from any cause or HF hospitalization compared to those without PH (56.1% vs. 19.5%; hazard ratio: 2.62; 95% confidence interval: 1.1 to 6.9; p=0.03). Multivariate Cox regression analysis showed that residual PH and higher PAWP after TEER were associated with higher mortality (hazard ratio: 1.14; 95% confidence interval: 1.03 to 1.28; p=0.01). Conclusion Our results suggest that patients with residual PH after TEER have a poor prognosis. Residual PH and high PAWP after TEER are associated with mortality.

Prognostic value of MELD-XI score and hemodynamic parameters in patients undergoing transcatheter tricuspid valve intervention

Abstract Background Hepatorenal dysfunction is a strong prognostic predictor in patients with tricuspid regurgitation. Patients are often hospitalized with acute heart failure due to volume overload and peripheral hypoperfusion. End-organ dysfunction is associated with the development of right ventricular failure related to hemodynamic changes such as low cardiac output and passive congestion from increased right ventricular filling pressures. Purpose This study aimed to investigate the prognostic value of hepatorenal dysfunction using the Model for End-stage Liver Disease (MELD) Score, the modified version of the score, MELD-XI, and of parameters determined during right-heart catheterization in patients undergoing transcatheter tricuspid valve intervention. Methods In this single-center prospective cohort study, data from patients undergoing edge-to-edge repair or heterotopic minimal invasive tricuspid valve repair were analyzed. Serum creatinine, INR and bilirubin were measured and the MELD score as well as the MELD XI score was calculated. All patients underwent right heart catheterization before the intervention. Receiver operator characteristics with calculation of the area under the curve (AUC) were performed to determine the predictive value of MELD (XI) score and hemodynamic parameters for the combined endpoint of rehospitalization due to decompensated heart failure and mortality within 3 months. Results Data from 36 consecutive patients were analyzed. 28 patients underwent edge-to-edge repair and 8 patients heterotopic minimal invasive tricuspid valve repair. Mean age of patients was 80.2 ± 5.9 years; 33.3% (12/36) were male. Baseline characteristics are shown in table 1. Rehospitalization due to decompensated heart failure occurred in 9/36 patients (25%). Mortality within the first 3 months was 11% (4/36). The predictive value for the composite endpoint of the modified MELD IX score was AUC 0.82 (95 % CI 0.63-0.99; p=0.009), while the conventional MELD score had an AUC of 0.77 (95 % CI 0.55-0.99; p = 0.059) (figure 1). RV pressure (AUC 0.84, 95% CI 0.66-1.00, p= 0.012) and RA pressure (AUC 0.83, 95% CI 0.67-0.98, p=0.016) showed a good predictive value for the composite endpoint (figure 2). The combination of MELD XI (at admission) and RV or PA pressure improved the AUC (MELD XI + RV: AUC 0.85; MELD XI + PA: AUC 0.84). Conclusion In this pilot-study, the modified MELD XI score, as indicator of hepatorenal dysfunction, was identified as a potential marker for short-term outcome after interventional tricuspid valve treatment.

Clinical implications of hepatorenal function in patients undergoing percutaneous coronary intervention: insights from the SAKURA PCI2 registry

Abstract Background Hepatorenal function is a prognostic predictor for heart failure, cardiac surgery, and transcatheter intervention for structural heart disease. However, the clinical implications of hepatorenal function assessed by the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score is still unclear in patients undergoing percutaneous coronary intervention (PCI). Purpose This study aimed to clarify the association between clinical prognosis and the MELD-XI score. Methods We analyzed 993 patients who underwent PCI from June 2020 to July 2022 in the SAKURA PCI2 registry, a prospective multicenter registry. Patients were stratified into high (>10) or low (≤10) MELD-XI scores. Primary outcome was defined as 2-year major adverse cardio or cerebrovascular event (MACCE), including all-cause death, ischemic stroke, and non-fatal myocardial infarction. Secondary outcome was defined as major bleeding according to the Bleeding Academic Research Consortium 3 or 5. Results Of study participating patients, 253 patients (25.5%) were stratified into a high MELD-XI score group and had a higher prevalence of the high bleeding risk than patients with a low MELD-XI score (92.5% vs. 53.7%, p<0.01). Patients with a high MELD-XI score were associated with MACCE (13.1% vs. 2.7%, p<0.01; adjusted HR 3.78, 95%CI 1.78-8.03, p<0.01) and major bleeding (4.0% vs. 1.3%, p<0.01: unadjusted HR 3.32, 95%CI 1.35-8.18, p=0.01). Moreover, these associations remained consistent in patients with chronic and acute coronary syndrome (MACCE, p for interaction=0.89; major bleeding; p for interaction=0.64). Conclusion A high MELD-XI score was associated with an increased risk of MACCE and major bleeding within two years. Therefore, the MELD-XI score could provide information for risk stratification in patients undergoing PCI.Outcomes

Cardiac damage predicts the outcome of calcific aortic valve disease regardless of the severity of aortic stenosis

Abstract Title: Cardiac damage predicts the outcome of patients with calcific aortic valve disease in both mild and moderate aortic stenosis Background Although the burden of calcific aortic valve disease (CAVD) is increasing, there is no current universal consensus for prognostic prediction. A staging system based on cardiac damage has been proposed to better stratify risk and evaluate the benefit of aortic valve intervention (AVI). Purpose We sought to evaluate this staging system’s prognostic value in mild and moderate aortic stenosis (AS). Methods Data from clinically indicated echocardiograms performed between 2010 and 2018 in patients aged over 18 years were extracted and linked to national outcome data. A time to first event analysis was performed with a primary outcome of mortality or heart failure hospitalization. Stages were categorized as described in previous literature: no extravalvular damage (stage 0); left ventricular damage (stage 1); left atrial damage (stage 2); elevated right ventricular pressures (stage 3); or right ventricular damage (stage 4). Results Amongst 24,699 patients in the study cohort, 513 had moderate AS and 920 had mild AS. Associated cardiac damage in those with moderate AS was graded as follows: Stage 0 - 9.4%; Stage 1 - 53.7%; Stage 2 - 31.1%; Stage 3 - 3.2%; Stage 4 - 2.6%. Increasing severity of CAVD correlated closely with increased risk of the primary outcome in both moderate (HR 1.62 per stage; 95% CI 1.36 – 1.92) and mild AS (HR 1.93 per stage; 95% CI 1.69 – 2.21), whilst increasing stage of cardiac damage was associated with mortality when censoring at the time of AVI in both moderate (HR 1.97 per stage; 95% CI 1.66 – 2.34) and mild AS (HR 2.06 per stage; 95% CI 1.81 – 2.35). Conclusion Cardiac dysfunction predicts prognosis to a similar extent in both mild and moderate AS. These data suggest that adverse outcomes may not be fully attributable to the haemodynamic consequences of valve disease, and therefore may not be reversed by valve intervention. Strategies to treat cardiac dysfunction in parallel with management of the anatomical valve pathology may be required.Mortality in mild AS by CAVD stageMortality in moderate AS by CAVD stage

Prognostic prediction of cardiovascular adverse events in patients after percutaneous coronary intervention using machine learning

Abstract Introduction While prevention of major cardiovascular adverse events (MACE) is important in the management of patients after percutaneous coronary intervention (PCI), risk stratification of MACE remains a significant challenge with increasingly diverse and complex patient backgrounds. In response to that, this retrospective observational study aimed to explore whether machine learning (ML) methods can predict future MACE after PCI using a variety of features extracted from electronic medical records (EMRs). Methods In 3,016 patients with coronary artery disease who performed PCI, 3 machine learning (ML) algorithms (gentle boost, random forest, and neural network) and statistical model were retrospectively applied to predict the occurrence of MACE within two years after PCI (564 patients, 18.7%). MACE was defined as composite endpoint of cardiac death, myocardial infarction (MI), any revascularization, and congestive heart failure (CHF). Basic patient information (e.g., age, sex, coronary risk factors) and laboratory test results were used for the analysis. Feature importance was calculated to identify key factors for MACE. Hold-out method with an 8:2 split between training and test was used to calculate sensitivity, specificity, positive predictive value, negative predictive value, and F-value for each model. Results As shown in Figure 1, ML models showed excellent diagnostic accuracies in the prediction of MACE after PCI, demonstrating higher F-values compared with statistical model (logistic regression analysis). Similar results were seen in the subgroup analyses for estimating cardiac death, MI, revascularization, or CHF. Although the weighting of feature importance for MACE recurrence varied among ML models, infarct size (peak CK levels), increased inflammatory status, and traditional coronary risk factors were identified as important features for predicting MACE within two years after PCI (Figure 2). Conclusions It is suggested that ML using EMRs is promising for inferring future MACE within two years after PCI. Further studies are warranted to address whether ML-based risk stratification could lead to improved clinical decision-making after PCI.

Development and validation of a predicting model for risk of mortality in heart failure patients with mildly reduced ejection fraction post discharge

Abstract Background Prognostic prediction for heart failure with mildly reduced ejection fraction (HFmrEF) patients remains challenging. We aimed to create and validate a mortality risk prediction model for HFmrEF patients at 6-month, 1-year, and 3-year post discharge. Methods Clinical data of 1691 HFmrEF patients registered in the heart failure registry from 2015 to 2020 at the Heart Center of our hospital were analyzed. Patients were assigned into a training (1183 patients) and validation cohort (508 patients) at 7:3 ratio. Predictive variables for mortality at various period post discharge were identified by the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The predicting model was then established based on these variables. Model performance was evaluated with ROC curve and Decision Curve Analysis (DCA). Results Eight predictors were identified including age, NT-proBNP, hemoglobin levels, use of beta-blockers, ACEI/ARB, invasive ventilation, PCI procedures, and pulmonary artery systolic pressure values. The model achieved a C-index of 0.748 (training set) and 0.755 (validation set). Area Under the Curve (AUC) for training set at 6 months, 1 year, and 3 years were 0.813, 0.784, and 0.774, and AUC for validation set were 0.775, 0.744, and 0.770, respectively. The DCA analysis confirmed the favorable net benefit of the established nomogram model. Conclusion This predicting model might be used for post-discharge risk stratification and individual decision-making of post-discharge management in HFmrEF patients.

Association of R2-CHA2DS2-VASc score and clinical outcomes after bioprosthetic valve replacement: Subanalysis from BPV-AF registry

Abstract Background Although bioprosthetic valve (BPV) replacements are becoming more common, there are limited studies about prognostic prediction method for patients after BPV replacement. R2-CHA2DS2-VASc score is modified CHA2DS2-VASc score by adding reduced estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2). It is increasingly used for the prediction of cardiovascular (CV) events in patients with atrial fibrillation (AF), device implantation, and acute coronary syndrome. Purpose We aimed to evaluate the predictive value of R2-CHA2DS2-VASc score for future CV events in patients after BPV replacement. Methods BPV-AF, an observational, multicenter, prospective registry, enrolled AF patients that underwent BPV replacement. Patients were stratified into three risk groups according to their R2-CHA2DS2-VASc score as follows; low (scores, 0–1), moderate (scores, 2–4), and high (scores, 5–11). The primary outcome measure was a composite of stroke, systemic embolism, CV events including heart failure hospitalization, and cardiac death. Results A total of 766 patients were included in the analysis. The mean age was 80.3 years and 419 patients (54.7%) were female. Mean R2-CHA2DS2-VASc score was 4.1±1.5. Low, moderate, and high R2-CHA2DS2-VASc score groups consisted of 12 (1.6%), 178 (23.2%), and 576 (75.2%) patients, respectively. Median follow up period was 491 (interquartile range: 393-561) days. Kaplan-Meier analysis showed higher incidence of the composite CV events in high R2-CHA2DS2-VASc score group (Log rank test; p<0.01). Multivariate Cox proportional hazards regression analysis revealed that the R2CHA2DS2-VASc score as a continuous variable was an independent predictor of CV events (hazard ratio 1.33, 95% confidence interval 1.18 to 1.51, p<0.01). Conclusion The R2-CHA2DS2-VASc score is useful for CV risk stratification in AF patients after BPV replacement.Cumulative Incidence for Composite CV Ev

Artificial intelligence assessment of heart failure and mortality after acute stroke

Abstract Background/Introduction The adverse cardiovascular outcomes following a stroke have shown significant associations with post-stroke mortality. However, studies focusing on predicting heart failure and its impact on long-term mortality are scarce. Purpose To address this gap, we employed an commercially approved artificial intelligence/machine learning enabled software as a medical device (AiTiALVSD version 1.00.00) which uses only 12 lead electrocardiogram data, resulting probability score for predicting left ventricular systolic dysfunction. We derived the AiTiALVSD probability score from initial ECGs at stroke admission, and assess its implications for prediction of heart failure and long-term mortality. Methods We collected data from 335 ischemic stroke patients admitted to a cardiovascular center during acute periods between 2013 and 2019. The AiTiALVSD score was employed to predict heart failure with reduced ejection fraction and heart failure with mild reduced ejection fraction, analyzed through logistic regression. Subsequently, we used the Cox Hazard proportional model, incorporating the AiTiALVSD score and clinical factors, to predict long-term mortality. Results The model incorporating the AiTiALVSD score with clinical variables demonstrated a higher AUC for predicting heart failure (0.905 [95% CI, 0.827-0.927] vs. 0.828 [95% CI, 0.749-0.907], p<0.004) than clinical variables alone. Moreover, for long-term mortality prediction, this model outperformed the conventional mortality score (AUC, 0.884 [95% CI, 0.836-0.933] vs. 0.755 [95% CI, 0.690-0.820], p<0.001). Conclusion Multivariable models which combine the AiTiALVSD score with clinical factors, effectively predicts heart failure and long-term mortality. This model could enhance therapeutic strategy tailoring by providing acute phase prognostic predictions for individual stroke patients.Prediction performance for heart failurePrediction performance for mortality

Expression of lipid-metabolism genes is correlated with immune microenvironment and predicts prognosis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. This study was aimed to identify a lipid metabolism-related signature associated with the HCC microenvironment to improve the prognostic prediction of HCC patients. Clinical information and expression profile data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, including the GEO dataset GSE76427. The gene expression profile of lipid metabolism was downloaded from Molecular Signatures Database (MSigDB) database. The infiltrating immune cells were estimated by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), MCP-counter, and TIMER algorithms. Functional analysis, including Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene set enrichment analysis (GSEA) were performed to elucidate the underlying mechanisms. The prognostic risk model was performed by Least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis. Two distinct subgroups of survival were identified. Better prognosis was associated with high immune score, high abundance of immune infiltrating cells, and high immune status. GO and KEGG analysis showed that differentially expressed genes (DEGs) between the two subgroups were mainly enriched in immune related pathways. GSEA analysis suggested that the expression of lipid metabolism related genes (LMRGs) was related to dysregulation of immune in the high-risk group. Risk models and clinical features based on LMRGs predicted HCC prognosis. This study indicated that the lipid metabolism-related signature was important for the prognosis of HCC. The expression of LMRGs was related to the immune microenvironment of HCC patients and could be used to predict the prognosis of HCC.

Left atrial reservoir strain as a prognostic indicator for cardiovascular events after mitral valvuloplasty

Abstract Background In patients after mitral valvuloplasty (MVP), assessing valve function and heart failure (HF) is crucial for prognostic predictions. Left ventricular diastolic function assessed by transthoracic echocardiography (TTE) plays an important role in the evaluation of HF in general practice. However, post-mitral valve surgery patients are excluded from the left ventricular diastolic function assessment guidelines proposed by the American Society of Echocardiography in 2016 due to their low correlation with left ventricular diastolic function indices. On the contrary, the left atrial reservoir strain (LARS) before MVP is considered as a prognostic factor, reflecting left atrial dysfunction caused by mitral regurgitation. Nevertheless, there are limited reports on the relationship between LARS and cardiovascular (CV) events after MVP. Purpose The study aims to investigate the utility of LARS in predicting CV events after MVP. Methods The study included 249 patients who underwent TTE between January 2011 and January 2023 after MVP at our hospital. Patient background data, including NYHA classification, medical history, medications, blood tests, and TTE data, were collected at the time of follow-up TTE. LARS, left ventricular global longitudinal strain (LV-GLS), and right ventricular free wall strain (RV-FWSL) analysis were performed using a vender-independent external strain analysis software for all patients in the cohort. The primary endpoints were cardiovascular death and HF rehospitalization. The predictor of cardiovascular events was assessed using the Cox proportional hazards model and Kaplan-Meier curve (KMC). Results The mean age was 61±14 years, and 159 patients (64%) were male. The median time from surgery to TTE was 4.8 (1.0-6.8) years, 32 patients (13%) had events within 8.5 (3.7-10.8) years after TTE. The event groups had higher age, NYHA classification, and NT-pro BNP compared to the non-event group. TTE parameters such as left ventricular mass index, left ventricular end-diastolic volume and end-systolic volume were larger, and LV-GLS and LARS were significantly lower in the event group. In multivariate Cox proportional hazards models showed that LARS was also a prognostic indicator even after adjustment for several variables (Table 1). The KMC showed that LARS was associated with events regardless of left atrial volume index (Log-rank p <0.001, chi-square:31.03) (Figure 1). Conclusion LARS was strongly associated with CV events after MVP. We consider LARS to be a useful prognostic indicator after MVP.

Identification of lncRNA dual targeting PD-L1 and PD-L2 as a novel prognostic predictor for gastric cancer

BackgroundAlthough breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC.MethodsThe transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal–wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA–PD-L1/PD-L2 axis were verified by dual luciferase reporter assay.ResultsTwenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094–miR-17-5p–PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094–miR-17-5p–IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2.ConclusionLINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

Characterizing adipocytokine-related signatures for prognosis prediction in prostate cancer

BackgroundProstate cancer (PCa) is a prevalent malignant tumor in males, with a significant incidence of biochemical recurrence (BCR) despite advancements in treatment. Adipose tissue surrounding the prostate, known as periprostatic adipose tissue (PPAT), contributes to PCa invasion through adipocytokine production. However, the relationship between adipocytokine-related genes and PCa prognosis remains understudied. This study was conducted to provide a theoretical basis and serve as a reference for the use of adipocytokine-related genes as prognostic markers in PCa.MethodsTranscriptome and survival data of PCa patients from The Cancer Genome Atlas (TCGA) database were analyzed. Differential gene expression analysis was conducted using the DESeq2 and limma packages. Prognostic genes were identified through univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. A prognostic model was developed and validated utilizing receiver operating characteristic (ROC) and Kaplan-Meier (K-M) curves. Assessments of immune cell infiltration and drug sensitivity were also carried out. Subsequently, the function of BNIP3L gene in PCa was verified.ResultsA total of 47 adipocytokine-related differentially expressed genes (DEGs) were identified. Five genes (PPARGC1A, APOE, BNIP3L, STEAP4, and C1QTNF3) were selected as prognostic markers. The prognostic model demonstrated significant predictive accuracy in both training and validation cohorts. Patients with higher risk scores exhibited poorer survival outcomes. Immune cell infiltration analysis revealed that the high-risk group had increased immune and ESTIMATE scores, while the low-risk group had higher tumor purity. In vitro experiments confirmed the suppressive effects of BNIP3L on PCa cell proliferation, migration, and invasion.ConclusionThe prognostic model independently predicts the survival of patients with PCa, aiding in prognostic prediction and therapeutic efficacy. It expands the study of adipocytokine-related genes in PCa, presenting novel targets for treatment.