Predictor Of Survival Research Articles

Prognostic Value of Systemic Inflammatory Response in Lymph Node-Negative Colorectal Cancer.

The aim of this study was to investigate the prognostic value of systematic inflammatory response in patients with lymph node-negative colorectal cancer. We retrospectively investigated 245 patients with lymph node-negative colorectal cancer who underwent curative resection and evaluated the prognostic impact of systematic inflammatory response, which was represented by neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and C-reactive protein-to-albumin ratio (CAR). Then, the prognostic significance of the systematic inflammatory response on survival was analyzed using the Kaplan-Meier method in patients selected by propensity score matching (PSM) analysis. In the multivariate analysis, CAR ≥ .081 (P = .004) was independent predictors of disease-free survival, while American Society of Anesthesiologists physical status ≥3 (P = .049) and CAR ≥ .081 (P < .001) were independent predictors of overall survival. By PSM analysis, PSM-high-CAR was significantly associated with worse disease-free survival (P = .043) and overall survival (P = .041) in patients with lymph node-negative colorectal cancer. C-reactive protein-to-albumin ratio may be a significant indicator of poor long-term outcomes in patients with lymph node-negative colorectal cancer.

Disease-free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant therapy

Disease-free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant therapy

Population Pharmacokinetic Modeling and Exposure-Response Analysis for the Antibody-Drug Conjugate Enfortumab Vedotin in Locally Advanced or Metastatic Urothelial Carcinoma.

Enfortumab vedotin is a fully human monoclonal antibody directed to Nectin-4 and conjugated to monomethyl auristatin E (MMAE), approved for treatment of previously treated locally advanced or metastatic urothelial carcinoma (mUC). This population analysis characterized pharmacokinetics of enfortumab vedotin and free (unconjugated) MMAE, identified covariates affecting pharmacokinetics, and evaluated weight-based dosing for enfortumab vedotin. Exposure-response analyses characterized relationships between enfortumab vedotin and free MMAE exposures and efficacy/safety endpoints. Data from 748 patients with locally advanced or mUC in 5 clinical studies were analyzed using nonlinear mixed-effects modeling. Patients received enfortumab vedotin 0.50-1.25 mg/kg every 3 weeks or on days 1, 8, and 15 of a 28-day cycle. Relevant covariates retained in final models were evaluated for clinical relevance to enfortumab vedotin and free MMAE exposures. Although some covariates produced differences in exposure, the magnitude of changes was not clinically meaningful. Simulations indicated weight-based dosing yielded more consistent exposures across body weight groups vs. a hypothetical fixed-dose regimen of enfortumab vedotin 95 mg (calculated for median body weight, 75 kg). Exposure-response analysis showed average enfortumab vedotin concentrations were not a statistically significant predictor of overall survival (hazard ratio 0.91, 95% confidence interval: 0.72-1.14; P = 0.41); all exposure quartiles had a greater median overall survival than chemotherapy (11.0-12.6 vs. 9.0 months). Enfortumab vedotin and free MMAE exposures were statistically significant predictors of grade ≥ 3 treatment-related adverse events (both P < 0.0001). This analysis supports enfortumab vedotin 1.25 mg/kg on days 1, 8, and 15 of a 28-day cycle.

Breast cancer survival prediction using an automated mitosis detection pipeline.

Mitotic count (MC) is the most common measure to assess tumor proliferation in breast cancer patients and is highly predictive of patient outcomes. It is, however, subject to inter- and intraobserver variation and reproducibility challenges that may hamper its clinical utility. In past studies, artificial intelligence (AI)-supported MC has been shown to correlate well with traditional MC on glass slides. Considering the potential of AI to improve reproducibility of MC between pathologists, we undertook the next validation step by evaluating the prognostic value of a fully automatic method to detect and count mitoses on whole slide images using a deep learning model. The model was developed in the context of the Mitosis Domain Generalization Challenge 2021 (MIDOG21) grand challenge and was expanded by a novel automatic area selector method to find the optimal mitotic hotspot and calculate the MC per 2 mm2. We employed this method on a breast cancer cohort with long-term follow-up from the University Medical Centre Utrecht (N = 912) and compared predictive values for overall survival of AI-based MC and light-microscopic MC, previously assessed during routine diagnostics. The MIDOG21 model was prognostically comparable to the original MC from the pathology report in uni- and multivariate survival analysis. In conclusion, a fully automated MC AI algorithm was validated in a large cohort of breast cancer with regard to retained prognostic value compared with traditional light-microscopic MC.

Prognostic and therapeutic implications of low aortic valve calcium score in patients with low gradient aortic stenosis.

Low gradient (LG) aortic stenosis (AS) poses a diagnostic challenge. Aortic valve calcium score (AVCS) assessment has emerged as a complementary diagnostic method when echocardiography provides discordant results. However, the diagnostic and prognostic value of AVCS in LGAS has not been thoroughly studied. Our aims were to investigate the prognostic importance of AVCS in LGAS and to assess whether symptomatic patients with LGAS and low AVCS may benefit from aortic valve intervention (AVI). 327 symptomatic patients (78.5±7.3 years, 51% women) with severe AS defined by the aortic valve area who underwent computed tomography for transcatheter aortic valve intervention (TAVI) planning were enrolled. AVCS was measured. AVCS<2000 AU in men and<1200 AU in women was considered low AVCS. 243 patients had high gradient (HG) and 84 had LGAS. Low AVCS was present in 25(10%) of the HG and 34(40%) of the LGAS cases. Over a median follow-up period of 4.9 years, 194 deaths occurred. In multivariate analysis, AVCS was a significant independent predictor of all-cause mortality among HGAS (aHR:2.317; CI:1.104-4.861; p= 0.026), but not among LGAS (aHR:0.848; CI:0.434-1.658; p=0.630) patients. After propensity score matching between patients who underwent AVI and those who were medically treated, AVI (94% TAVI) was a significant and independent predictor of survival among LG AS patients with low AVCS even after adjustment for clinical variables (aHR:0.102, CI:0.028-0.369; p<0.001). The prevalence of low AVCS is much higher in LGAS than in HGAS. In symptomatic severe LGAS low AVCS did not entail a better prognosis. AVI is equally beneficial in LGAS patients with high or low AVCS, similarly to HGAS.

Multi-modal artificial intelligence-based prediction for cardiovascular mortality after transcatheter aortic valve implantation: a time-to-event survival prediction

Abstract Background Predicting long-term outcomes following Transcatheter Aortic Valve Implantation (TAVI) presents a significant challenge. Objective We aimed to predict post-TAVI long-term cardiovascular mortality using multimodal data and employing time-to-event artificial intelligence (AI) algorithms. Methods This study enrolled 3,973 consecutive patients from the prospective TAVI registry (between August 2007 and June 2023). Multimodal information was collected and extracted as numerical data for each patient, encompassing clinical history, medication, laboratory, procedural characteristics, ECG, angiography, echocardiography (TTE and TEE), and CT. Clinical outcomes were adjudicated by an independent clinical event committee. From the multimodal information, 147 features were extracted at baseline before the TAVI procedure. The datasets were divided into a training/validation set (80%) and a hold-out test set (20%) for model development and evaluation, respectively. Cox-LASSO feature selection was employed to identify the most relevant features, followed by the implementation of Random Survival Forest (RSF), Gradient Boosting Survival Analysis (GBSA), and Survival Support Vector Machine (SSVM) to predict the timing and occurrence of cardiac death events in patients. Feature selection, model parameters, and hyperparameters selection were performed using 10-fold cross-validation on the training set. Model performance was evaluated using different metrics, such as the concordance index (c-index) and cumulative Area Under the Curve (C-AUC) on a 20% untouched test set. Results In the patient cohort, 28.4% experienced cardiovascular death. Features were selected from various modalities, including 22 from clinical history, two from medication, eight from laboratory tests, one from ECG, eight from CT scans, and five from echocardiography and angiography. In the univariate Cox-PH model, all features exhibited a C-index ranging from 0.50 to 0.57. In the test set, the conventional Multivariate Cox-PH model achieves a c-index of 0.59 (C-AUC: 0.56). RSF, GBSA, and SSVM achieve a C-index of 0.70 (C-AUC: 0.69), 0.66 (C-AUC: 0.64), and 0.69 (C-AUC: 0.68), respectively, in the holdout test set. Conclusion Integrating multimodal information, encompassing imaging, signal, laboratory data, and clinical history, with AI algorithms has markedly enhanced the prediction of long-term cardiac outcomes following the TAVI procedure. The initially developed model can predict the probability of cardiac death up to 10 years. Furthermore, the RFS model significantly outperformed the conventional Cox model in predicting time-to-event outcomes.

CEBPA mutation in acute myeloid leukemia: prognostic impact of bZIP domain mutation

Abstract One of the most important prognostic genes for acute myeloid leukemia (AML) is CEPBA, and its mutation (CEBPAmu) is present in nearly 10%–15% of de novo AML cases. CEBPAdm is associated with a favorable prognosis; however, CEBPAsm does not appear to have a better prognosis than CEBPAdm. We reviewed CEBPAmu-bZIP in 8694 cases across studies for prognostic impact in patients with de novo AML. It was observed that CEBPAmu in the basic leucine zipper domain (bZIP) was strongly associated with a favorable prognosis, but CEBPAmu out of the bZIP domain was not. CEBPA-bZIP mutations were discovered in 562 (6.46%) of 8694 cases, with 366 (65.1%) harboring a second CEBPA mutation (CEBPA-double-mutated [CEBPAdm]) and 196 (34.9%) having a single CEBPA-bZIP only mutation. Multivariate analysis of three studies consisting of 1028, 4708, and 2958 patients showed that CEBPAmu in bZIP was the most potent predictor of overall survival (OS) with overall survivability of 53%, 62%, and 89%, respectively, independently. However, complete remission of disease with bZIP mutation in the same studies was found to be 80%, 62%, and 78.6%, respectively. These findings indicate that CEBPAmu in bZIP is a potent marker for AML prognosis.

Gender differences in long-term survival after coronary artery bypass surgery is womens cardiovascular health at risk?

Abstract Introduction Cardiovascular healthcare for women tends to be influenced by various factors. This patient group is generally associated with a worse prognosis following coronary artery bypass surgery (CABG). Aims To assess the impact of gender on long-term survival after CABG and the potential effect of age on this association; to compare the survival of these patients with the expected survival of the general national population, and to compare immediate postoperative outcomes between genders. Methods Longitudinal, retrospective, single center study, involving consecutive patients who underwent isolated primary CABG between 2004 and 2014. Exclusion criteria included emergency/salvage surgeries or the use of extracorporeal circulation without aortic clamping. Included patients were categorized into age subgroups: ≤60, 60-70, and ≥70 years. All-cause mortality was assessed in February 2023, and a time-to-event analysis was performed using Kaplan-Meier curves, Log-Rank tests, and multivariable Cox regressions. To compare expected mortality (matched for sex and age with the general population) with observed mortality in the patient cohort, survival tables for the years 2004-2022 were consulted. Kaplan-Meier curves for the reference population, stratified by gender, were constructed and compared to the surgical cohort using one-sample Log-Rank tests with specific software. Standardized mortality ratios (SMR) were estimated. The mean follow-up time was 11 years, with a maximum of 19 years. Results From 3978 patients included patient’s, 21% were women (W). W were older (mean age 67±9 vs. 63±10 years, p&amp;lt;0.001) and had a higher prevalence of cardiovascular risk factors and severe chronic kidney disease compared to men (M). M more frequently had peripheral arterial disease and smoking habits. Although three-vessel disease was similar between sexes (p=0.111), W were less frequently implanted with ≥3 grafts (p&amp;lt;0.001). At 5,10 and 15 years of follow-up, cumulative survival for MvsW was 89%vs88%, 73%vs68%, and 57%vs46%, respectively (Log-rank test p&amp;lt;0.001). After stratification by age, Log-Rank tests showed no differences between sexes. Multivariable adjustment did not identify gender as an independent predictor of long-term survival in any age subgroup. However, a time-stratified analysis at 10 years of follow-up in the ≥70 years subgroup showed that W had a higher risk than M after 10 years of follow-up (HR:0.7[0.5-0.9],p=0.03). Comparing with the survival of the Portuguese population, CABG allowed M to equalize the risk of mortality to what was expected (SMR =1.1;95%CI:0.9-1.1), but W showed a higher risk of mortality after CABG than W in the reference population (SMR =1.6,95%CI:1.3-1.8). Conclusion Women undergoing isolated primary CABG at an age &amp;gt;70 years, with longest periods follow-up, exhibited poorer long-term survival than men of the same age.Women demonstrated inferior survival outcomes compared to the general population.

Prognostic significance of systemic pan-immune-inflammation value in locally advanced cervical cancer

ObjectiveThis study investigates the significance of systemic pan-immune inflammation value (PIV) prior to concurrent chemoradiotherapy (CCRT) in predicting the therapeutic efficacy as well as prognosis of patients with locally advanced cervical squamous cell carcinoma.MethodsA retrospective analysis was conducted on the clinical data of 847 patients with locally advanced cervical cancer (LACC) treated at the Second Hospital of Jilin University between 2016 and 2020. All patients underwent radical CCRT, including platinum-based sensitizing chemotherapy. The PIV was measured as given by: (platelet count × neutrophil count × monocyte count)/lymphocyte count. Logistic regression analysis was utilized to study the effect of PIV on therapeutic response in LACC patients and Kaplan–Meier survival together with Cox proportional hazard model to assess its impact on prognosis.ResultsWith the therapeutic effect as the endpoint, the optimal cutoff of PIV (356.0099) was signified via the receiver operating characteristics curve, and patients were grouped and compared based on this value. PIV was determined as an independent predictor of the therapeutic effect in CCRT for LACC (hazard ratio (HR) 1.696, 95% confidence interval (CI) 1.111–2.590). PIV was also an independent predictor of overall survival (OS) (HR 0.540, 95% CI 0.409–0.713, p&amp;lt;0.001) as well as disease-free survival (DFS) (HR 0.680, 95% CI 0.528–0.876, p=0.003). Compared to the low-PIV group, it was noted that individuals with a high PIV exhibited a poorer therapeutic effect and shorter OS and DFS.ConclusionPatients with LACC and high PIV had poorer therapeutic outcomes and shorter OS and DFS. Our results may provide PIV as a new prognostic biomarker for LACC, if future prospective studies with large patient numbers support our findings.

Risk nomogram for papillary thyroid microcarcinoma with central lymph node metastasis and postoperative thyroid function follow-up

BackgroundThe treatment for papillary thyroid microcarcinoma (PTMC) is controversial. Central lymph node metastasis (CLNM) is one of the main predictors of recurrence and survival, accurate preoperative identification of CLNM is essential for surgical protocol establishment for PTMC. The objective of this study was to establish a nomogram to predict the possibility of CLNM in PTMC patients.MethodsA total of 3023 PTMC patients were randomly divided into two groups by a ratio of 7 to 3, the training group (n = 2116) and validation group (n = 907). The LASSO regression model and multivariate logistic regression analysis were performed to examine risk factors associated with CLNM. A nomogram for predicting CLNM was established and internally validated. Meanwhile, we follow-up the serum thyroid function FT3, FT4, TSH, Tg, TGAb and TPOAb in 789 PTMC patients for 4 years after surgery and compared the differences between the CLNM (+) and CLNM (-) groups, respectively.ResultsThe LASSO regression model and multivariate logistic regression analysis showed that younger age, lower BMI, being male, location in the lower pole, calcification, 1 ≥ diameter ≥ 0.5 cm, multifocality lesions, extra thyroidal extension (ETE), enlargement of central lymph node (ECLN), lateral lymph node metastasis (LLNM) and higher carcinoembryonic antigen were the ultimate risk factors for determining CLNM. A nomogram for predicting CLNM was constructed based on the influencing factors and internally validated. By establishing the prediction model, the AUC of CLNM in the training and validation groups were 0.73 (95% CI, 0.70-0.76) and 0.75 (95% CI, 0.71-0.79) respectively. Results of the DCA showed that the model is clinically useful when deciding on intervention in the most range of the threshold probability. A 4-year follow-up of thyroid function showed that FT3 and FT4 remained at stable levels after 3 months postoperative and were higher in the CLNM (+) group than in the CLNM (-) group. Hypothyroidism appeared predominantly within 3 months after surgery. The overall incidence of the CLNM (+) group and CLNM (-) groups were 16.46% and 12.04%, respectively.ConclusionThe nomogram model constructed in this study has a good predictive effect on CLNM in PTMC patients and provides a reasonable reference for clinical treatment.

Interplay between strain pattern-based classification of dyssynchrony and myocardial scar in CRT patients

Abstract Introduction Echocardiography-derived septal strain patterns are valuable for predicting volumetric reverse remodelling and survival in patients undergoing cardiac resynchronization therapy (CRT). Nevertheless, presence of myocardial scarring in the left ventricle (LV) is known to attenuate CRT treatment response. Purpose This study aims to investigate the interplay between septal strain patterns and myocardial scarring in CRT candidates, and how they link to outcome after CRT. Methods In this prospective multicentre study, CRT candidates from five European institutions underwent pre-implantation assessments using speckle-tracking strain analysis on echocardiography and cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE). Dyssynchrony was graded through analysis of septal strain curves, categorizing patients into five distinct patterns, denoted as strain Stage-0 through strain Stage-4 (Fig. A). LGE of the LV wall was quantitatively assessed using CMR (as a percentage). The study endpoints were volumetric reverse remodelling (volume responder = more than 15% decrease LV end-systolic volume) after one year, and all-time all-cause mortality. Results A total of 267 patients, with a mean age of 66±11 years (69% males, 90% left bundle branch block [LBBB]) presented with an average LV ejection fraction (EF) of 30±7%. With each stepwise increase in strain stage, global LV scarring decreased (p&amp;lt;0.01; Fig. B) and the proportion of volume responders increased (all p&amp;lt;0.0001; Fig. C). ROC curves demonstrated that the predictive power of strain stages for CRT volumetric response was not significantly improved when scarring percentage was added (AUC 0.78 [95% CI: 0.69-0.83] vs. 0.81 [95% CI: 0.71-0.90]; p&amp;gt;0.05; Fig. D). In a multivariate cox regression model – including clinical characteristics that were significantly related to survival in univariate analysis – a patients’ strain stage was the only significant predictor of survival, also outperforming scar burden as determinant of outcome (HR 0.68; p=0.041; Fig. E). Conclusions Septal strain patterns show a strong association with the extent of reverse remodelling and outcome in CRT-treated patients. An inverse relationship is observed between pre-implant strain stages and the extent of myocardial scarring. However, scar burden did not provide incremental predictive value over the strain stages. Strain-pattern-based dyssynchrony assessment is a meaningful predictive marker which integrates information on myocardial dysfunction due to dyssynchrony as well as scar burden.

Right ventricular remodelling and long-term survival after pulmonary endarterectomy versus balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

Pulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH), while balloon pulmonary angioplasty (BPA) is an alternative for inoperable patients. We aimed to compare right ventricular (RV) remodelling and late survival after PEA and BPA. In this prospective observational cohort study, we performed echocardiography at baseline and follow-up in patients with CTEPH treated with PEA (n=54) or BPA (n=44) between 2011 and 2022. Follow-up echocardiography was performed at 5 months (IQR 4-7) after PEA and 3 months (IQR 2-4) after the last BPA. Both groups showed significant improvements in left ventricular end-systolic eccentricity index, RV basal diameter and RV fractional area change (RV FAC). Tricuspid regurgitation pressure decreased by 26±18 mm Hg after PEA and 13±21 mm Hg after BPA (p=0.02 for between-group difference). Tricuspid annular systolic excursion (TAPSE) decreased by 4±5 mm after PEA but increased by 1±4 mm after BPA (p<0.001). The TAPSE/systolic pulmonary artery pressure ratio improved similarly in both groups. Five-year survival was 96% (95% CI 86% to 99%) for PEA and 79% (95% CI 61% to 89%) for BPA (p=0.25). Change in RV FAC was an independent predictor of survival (HR 0.9, 95% CI 0.82 to 0.99, p=0.03). Both PEA and BPA led to significant RV reverse remodelling, with no clear evidence of a difference in survival rates. Improvement in RV function, particularly RV FAC, was associated with better outcomes, highlighting the importance of RV recovery in CTEPH treatment.

A two-point strategy to clarify prognosis in &amp;gt;80 year olds experiencing out of hospital cardiac arrest

Abstract Background The global population is aging, with the number of ≥80-year-olds projected to triple over the next 30 years. Rates of out-of-hospital cardiac arrest (OHCA) are also increasing within this age group. Purpose To assess predictors of survival to discharge in ≥80 year old people experiencing OHCA. Methods The Victorian Ambulance Cardiac Arrest Registry was utilised to identify OHCAs in patients aged ≥80 years between 2002-2021. Predictors of survival to discharge were defined and a prognostic score derived from this cohort. Results 77,628 patients experienced OHCA of whom 25,269 (32.6%) were ≥80 years (80-90 years=18,956; 90-100 years=6,148; &amp;gt;100 years=209). The number of patients ≥80 years increased over time both absolutely (p=0.002) and proportionally (p=0.028). 619 (2.4%) patients survived to discharge without change over time. Older ages had no difference in witnessed OHCA status but were less likely to have shockable rhythm (OR 0.50 (95% CI 0.44-0.57) for 90-100-year-olds, OR 0.28 (95% CI 0.12-0.63) for 90-100-year-olds). If OHCA was witnessed and there was a shockable rhythm then survival was 14%; if one factor was present survival was 5-6% and if neither factor was present, survival was 0.09%. These survival rates enabled derivation of a simplified prognostic assessment score – the ‘15/5/0’ score - highly comparable to a previously-published American cohort. Conclusions Elderly OHCA rates have increased to one-third of caseload. The most important factors predicting survival were whether the OHCA was witnessed and there was a shockable rhythm. We present a simple two-point ‘15/5/0’ prognostic score defining which patients will gain most from advanced resuscitative measures.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Electrocardiographic markers of depolarization and repolarization in lead V1 predict right ventricular dysfunction in patients with heart failure

Abstract Background Right ventricular (RV) dysfunction is an important predictor of survival in patients with heart failure (HF) with both preserved (HFpEF) and reduced ejection fraction (HFrEF). To date there is limited data on the value of the electrocardiogram in predicting RV function. Purpose Given these considerations the aim of our study was to assess the possible relationship between several electrocardiographic (ECG) parameters and right ventricular function evaluated by echocardiography. Methods We included 109 patients (age 61±14 years, 68men) of whom 89 had HF (HFpEF N=62 and HFrEF N=27) and 20 patients without HF. Twelve-lead ECG and echocardiograms were performed in all patients. We assessed echocardiographic parameters of global and regional RV function. Results Time to Intrinsicoid deflection in lead V1 (TID-V1) and the QTc interval measured in lead V1 (QTc-V1) were significantly more prolonged in patients with HF vs. patients with no HF (36±24ms vs. 23±15ms; p=0.03, and 450±40ms vs. 427±20ms; p=0.047 respectively). TID-V1 correlated significantly with the tricuspid annulus systolic excursion (TAPSE) and RV fractional area change (FAC; r=-0.31; p=0.02, and r=-0.35; p=0.029 respectively). QTc-V1 correlated with parameters of global and regional RV function including FAC, RV apex longitudinal strain, RV free wall strain, and global RV strain (r=-0.42; p=0.0004, r=0.35; p=0.0032, r=0.21; p=0.045, and r=0.41; p=0.0005). RV dysfunction as defined by RV-FAC&amp;lt;35% was predicted by TID-V1 &amp;gt; 30ms with a sensitivity of 61% and specificity of 75%; AUC=0.752 and by QTc-V1&amp;gt;440ms with a sensitivity of 80% and specificity of 57%; AUC=0.888, and by a multivariate logistic regression model that also included TID-V1 and QTcV1, age, TAPSE, and LV ejection fraction with an AUC=0.967 (Figure). Conclusions Lead V1 time to intrinsic deflection and QTc-V1 predict RV dysfunction independent of echocardiographic parameters of ventricular function in patients with HF.

Prognostic utility of heart-type fatty acid binding protein in patients with cardiac amyloidosis

Abstract Background Heart-type fatty acid binding protein (H-FABP) is a biomarker that has been shown to provide long-term prognostic information in patients with heart failure (HF), yet its role in patients with cardiac amyloidosis (CA) is unknown. Purpose We aim to investigate the association of H-FABP levels with prognosis in patients with CA. Methods Consecutive patients diagnosed with cardiac amyloidosis from October 2015 to May 2022 at Heart Failure Center, of our hospital were enrolled. Patients were categorized into 2 categories based on H-FABP levels measured in the baseline blood sample: &amp;lt; or = 7 ng/ml (low H-FABP), &amp;gt;7 ng/ml (high H-FABP). Univariate and multivariate Cox models were used to identify predictors of survival. Kaplan-Meier analysis was performed to compare survival between patients with low or high H-FABP. Results Overall, ninety-five patients were included. H-FABP was elevated (&amp;gt;7 ng/ml) in 37 patients (39%). Patients with high H-FABP were more likely to present with higher levels of high-sensitivity troponin-T (hs-TNT)(0.17ng/mL vs. 0.11ng/mL, p =0.01) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (18098.76pg/mL vs. 6211.69pg/mL, p&amp;lt;0.001). Patients were followed for an average follow-up period of 440 days, in which 53 (56%) patients died. Univariate and multivariate analysis demonstrated that H-FABP levels (HR 1.48, 95% CI 1.03-2.13, per 1-SD greater) was independently associated with prognosis, even after adjusting for NT-proBNP, hs-TNT and renal function. Conclusions Elevation of H-FABP is associated with an increased risk of death in patients with cardiac amyloidosis. H-FABP can serve as a novel biomarker independent of other established predictors for prognosis in cardiac amyloidosis.Kaplan-Meier curves for overall survival

Health care utilisation in patients with mild pulmonary hypertension - EVIDENCE-PAH UK study

Abstract Background ESC/ERS 2022 guidelines1, redefined precapillary pulmonary hypertension (PH) as patients with a mPAP&amp;gt;20mmHg,PVR&amp;gt;2WU and PAWP&amp;lt;15mmHg1.We and others identified patients with mildly elevated pulmonary artery(PA) pressures demonstrates a higher mortality2-4. It is important to understand healthcare resource utilisation(HRCU) in this newly defined group who now meet the thresholds for diagnosis, however, treatment options are limited. Purpose The EVIDENCE-PAH aims to describe mortality and hospitalisation outcomes, baseline demographics in mild elevations in PA pressure in a national cohort. We report preliminary analysis of HRCU from data obtained from NHS Hospital Episode Statistics(HES); inpatient admissions, outpatient(OP) and emergency attendances(AE). Method Retrospective analysis of all patients with a mPAP&amp;lt;25mmHg and a sample of patients with a mPAP≥25mmHg at index-right heart catheterisation(RHC), across all UK PH tertiary centres between 2009-2017 with hospitalisation data captured 24-months pre and post index-RHC. For analysis patients were categorised into 3 groups; normal haemodynamics(mPAP&amp;lt;21mmHg &amp; PVR≤2WU), mild elevation in haemodynamics(mPAP&amp;lt;21mmHg &amp; PVR&amp;gt;2WU, mPAP21-24mmHg with all PVR groups, mPAP&amp;gt;25mmHg &amp; PVR≤3WU) and abnormal haemodynamics(mPAP&amp;gt;25mmHg &amp; PVR&amp;gt;3WU). Results A total of 2413(82.3%) patients had complete records 24-months pre and post index-RHC; 561(23.2%), 1228(50.9%) and 624(25.9%) in the normal haemodynamic, mildly elevated haemodynamic and abnormal haemodynamic groups respectively. Figure 1, demonstrates HRCU; Unscheduled admissions are significantly higher in the abnormal haemodynamic group 24-months pre index-RHC compared to the normal/mild elevations in haemodynamic groups (p-value&amp;lt;0.05). There was reduction in unscheduled encounters 24-months post index-RHC in the normal/abnormal haemodynamic group. No significant difference identified in AE attendance and OP 24-months post across all haemodynamic groups. Total HRCU demonstrates a lower attendance 24-months post RHC in normal versus abnormal haemodynamic group (p-value&amp;lt;0.05). Multivariate analysis demonstrates unscheduled admissions 24-months pre/post index RHC, as an independent predictor of survival, adjusted for age, sex and haemodynamics (Figure 2;p-value&amp;lt;0.05). Conclusion Unscheduled admissions may act as a discriminator identifying advanced PH (abnormal haemodynamics), but not normal versus mild elevations in haemodynamics. Meanwhile AE and OP attendances fails to discriminate between normal and mild elevation in haemodynamics. Unscheduled admissions 24-months pre/post index RHC is an independent predictor of survival which may lend as a useful surrogate marker for mortality in the PH population as a whole. Although total HRCU appears high across haemodynamics groups referred to PH centre, in the 24-months post RHC HRCU increases in the mild/abnormal haemodynamic groups, this may represent ongoing unmet need in this group.

Beyond 2D echocardiography: A novel multiparametric assessment of right ventricular dysfunction in transcatheter tricuspid valve repair

Abstract Background Patients with severe tricuspid regurgitation (TR) are heterogenous and complex in terms of etiology, comorbidities and state of disease. Right ventricular (RV) function measured by RV to pulmonary artery coupling (RVPAc) is prognostic in transcatheter tricuspid valve repair (T-TEER). However, traditional 2D echocardiographic measures have critical limitations and RVPAc fails to respect the degree of volume overload/dilation of the RV, which is a key clinical tracer for right ventricular dysfunction (RVD). Purpose We aimed to refine RVPAc by incorporating RV dilation, assessed by 3D echocardiography, to improve the assessment of RV dysfunction for an enhanced outcomeprediction in T-TEER patients. Methods We analyzed 262 patients undergoing T-TEER with complete 3D echocardiography. Results Despite similar RV function across groups, RV dilation (HR 1.85; 1.10, 3.12; p=0.020) and impaired RV free wall longitudinal strain (RVFWLS, HR 1.73, 1.02, 2.92, p=0.042) predicted increased 1-year mortality. A novel RVPAc parameter [RVFWLS/(3D-RVEDV*sPAPinvasive)] was developed, associating RVPA-Uncoupling with a tripled risk of death (HR 3.19, 1.7-6.0, p&amp;lt;0.001). NYHA Class IV and the new RVPAc were independent mortality predictors after T-TEER, with the modified RVPAc showing superior predictive value over traditional RVPAc (c-index 0.68 vs. 0.57, p=0.027). Conclusion The novel RVPAc parameter, integrating RV dilation and function, is a powerful predictor of survival post-T-TEER, underscoring the importance of timely intervention in severe TR and RVD. 3D echocardiography plays a critical role in assessing RV dimension and function, with implications for the management and prognosis of TR patients.Central Figure

Peak VO2 is associated with cardiac functional response and long-term survival in patients with heart failure and atrial fibrillation undergoing catheter ablation

Abstract Background Contemporary guidelines recommend Catheter Ablation (CA) in patients with persistent Atrial Fibrillation (AF) with Heart Failure with reduced ejection fraction (HFrEF). It is challenging to prospectively predict who will respond. We have previously described the long-term survival outcomes of patients in this cohort.(1) However, the clinical characteristics associated with HF response and long-term clinical outcomes have not been reported. Objective To evaluate the association of HF parameters with cardiac functional response to CA and long-term survival after CA. Methods Post-hoc, long-term follow-up of mortality was undertaken in patients enrolled in the CAMTAF and ARC-HF RCTs. Both studies enrolled patients with persistent AF and HFrEF between 2005 and 2012 and randomised to first-time CA or medical therapy alone. Left ventricular ejection fraction (LVEF) and peak VO2 were measured in both studies at baseline and 12-month follow-up. The Universal Definition of HF response (LVEF improves by &amp;gt;10% points or to an LVEF &amp;gt;50%) was used.(2,3) Multi-variate logistic regression was used to determine features associated with HF response and Cox proportional hazards modelling for survival. Results 102 patients underwent randomisation with 52 assigned to CA. The mean age was 60.2 ±10.7 years with 93 (91.2%) male. The mean Baseline LVEF was 31 ±11% and peak VO2 was 1815 ±642mlmin-1. Baseline LVEF did not correlate significantly with Minnesota Living with Heart Failure (MLWHF) score (r=-0.11, p=0.29) whereas baseline peak VO2 did (r=-0.28, p&amp;lt;0.01). In patients randomised to CA, the median (IQR) improvement in LVEF was +8.4% (0, 15%). 22/52 (42.3%) patients were classified as Responders based on the Universal Criteria. Responders were younger (54.7 ±10.6 years vs 61.8 ±11.4, p=0.03) and had a higher mean HR on baseline Holter monitoring (89 ±14bpm vs 79 ±11bpm p&amp;lt;0.01) than non-responders. There was no significant difference in sex, baseline MLWHF scores, BNP levels or LVEF between groups (28±9% vs 31 ±9%, p=0.19). Responders had a significantly higher peak VO2 at baseline than Non-Responders (1972 ±668mlmin-1 vs 1556 ±580mlmin-1, p=0.03). On multivariate analysis, mean heart rate on Holter monitoring and peak VO2 were significantly associated with Responder status post-ablation. (Table 1a) During a median follow-up of 7.8 (3.9 –9.9) years, 34 (33.3%) patients died, including 17 (32.7%) patients in the CA arm. On univariate analysis, baseline peak VO2 was significantly greater of survivors at 5 years (1867 ±624 mlmin-1 vs 1259 ±497 mlmin-1, p&amp;lt;0.01). On multivariate Cox regression analysis, the peak VO2 at baseline was the only significant predictor of survival (Table 1b). Conclusion Peak VO2 at baseline was associated with baseline symptom status, the short-term LVEF response to CA and long-term survival and may be a useful stratification tool to aid patient selection for CA.1a. Regression for 6-month LVEF response1b. Regression for long-term mortality

Artificial intelligence-enhanced electrocardiography predicts 10-year risk of atherosclerotic cardiovascular disease

Abstract Background The ACC/AHA pooled cohort equations (PCE) calculates the 10-year primary risk of atherosclerotic cardiovascular disease (ASCVD), an indication to initiate primary prevention statin therapy in international guidelines. The validity of PCE is limited by its overestimation of risk in high-risk cohorts and an ethnic heterogeneity. Electrocardiography (ECG) has not been incorporated in current ASCVD risk estimation tools. Artificial Intelligence (AI)-based models are capable to capture patterns that are informative for cardiovascular prognosis. Purpose We explored the predictive value of a discrete-time survival model in 10-year ASCVD risk in comparison to PCE. Methods We developed an AI-ECG model to predict the 10-year ASCVD risk in an unselected secondary care population from the USA comprised of 1,163,401 ECGs from 189,539 patients. Data was split into training/validation and hold-out test sets by patient ID. Our AI-ECG model uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves, accounting for both time to event and censorship (i.e., loss to follow up). We compared the performance of out AI-ECG model using a subset of outpatient data (n=4590) of the BIDMC dataset to PCE and ASCVD risk factors including systolic blood pressure, total cholesterol, HDL cholesterol, hypertension, smoking history, diabetes mellitus, and ethnicity. Performances were evaluated using cox survival analysis. Our AI-ECG model was externally validated in the UKB Biobank (UKB), where we compared the performance of our AI-ECG model to predictions of existing AI-ECG models such as the Stanford Estimator of Electrocardiogram Risk (SEER) model. Results Our AI-ECG successfully predicted future ASCVD events in individuals (C-index 0.721 (0.719-0.723), 5-year AUC 0.761 (0.758-0.763), and differentiated between high and low risk group with an adjusted HR of 2.33 (2.26-2.41). Upon internal validation our AI-ECG model showed a superior performance (C-index 0.679 (0.651-0.708)) than PCE (0.605 (0.577-0.634)) and all risk factors combined (C index 0.642 (0.613-0.672)). When combining AI-ECG predictions with all risk factors, the model showed additional predictive value (0.686 (0.657-0.715)) (Figure 1). Our AI-ECG model showed modest predictive value within the UKB dataset (C-index 0.655 (0.637-0.673)), but significantly outperformed the SEER model (C-index 0.547 (0.527-0.567), p &amp;lt;0.0001 for comparison with AIRE). Conclusion We have shown the potential of AI-ECG models in predicting future ASCVD risks. AI-ECG models demonstrated accurate discrete time survival prediction and good classification performance superior to that of the SEER model, as well as PCE and ASCVD risk factors. . Accurate risk assessment of ASCVD may help prevent adverse events in high risk subjects and save unnecessary pharmacological interventios in low risk subjects.Figure 1