ROC Curve Analysis Research Articles

Abstract 33: A Novel Imaging Biomarker to Make Precise Outcome Predictions for Patients with Acute Ischemic Stroke

Introduction: Net water uptake (NWU) is a novel biomarker which measures edema and tissue injury from the degree of hypoattenuation on non-contrast CT and may serve as a precision tool for predicting outcomes after acute ischemic stroke (AIS). Using our recently developed algorithm, this study aimed to evaluate the relationship between NWU and post-stroke neurologic outcomes, including language impairment and motor weakness. Methods: Consecutive patients treated for AIS at certified stroke centers in Houston, TX were included. Patients’ precise functional outcomes at hospital discharge were recorded including decreased level of consciousness, presence of language impairment, visual deficit, arm and leg weakness, need for walking assistance, and gastrostomy placement. The primary outcome for this study was the performance of calculated NWU and clinical variables to predict language impairment at discharge. Baseline characteristics were compared, and then univariate and multivariate logistic regression were used to evaluate the association between clinical variables, imaging data, and the precise neurological outcomes. Results: Among 776 patients with AIS, average age was 67.0 +/- 14.8, 47.8% were female, median NIHSS was 10 [5,18], median ASPECTS was 9 [7,10], 42.6% received tPA, and 67.1% had a large vessel occlusion (see Table 1). In univariate logistic regression, higher NWU (OR 1.45, CI 1.30-1.63) and lower ASPECTS (OR 0.68, CI 0.63-0.74) were both significantly associated with higher likelihood of language impairment and other deficits at discharge (see Table 2). Additionally, higher NWU in all ten regions was significantly associated with deficit at discharge. In multivariate logistic regression, certain clinical and imaging variables remained significantly associated as described in Table 3. The ASPECTS and NWU-based regression models were directly compared when predicting language impairment using ROC curve analysis, and areas under the curve were 0.838 vs. 0.851 respectively (p = 0.152 with Delong test, see Figure 1). Conclusion: The novel NWU biomarker was significantly associated with precise post-AIS outcomes at discharge. When controlling for confounders, NWU was non-inferior to ASPECTS. Moving forward, region-based and overall NWU will need to be studied with long-term patient outcomes. Ultimately, this novel and open-access imaging biomarker could be used in the emergency setting to guide treatment decision-making and patient counseling.

Thermographic images for screening oral health problems in older adults: A pilot study

ObjectiveThis pilot study assessed the feasibility of using facial thermography to detect intra-oral problems in older adults with cognitive decline and care-resistant behaviors, who are often unable to communicate pain or early symptoms. MethodsTwenty-three older adults (mean age 73.7 ± 13.2 years) with cognitive decline were enrolled. Thermal images of four facial views were taken using a smartphone-connected FLIR thermal camera. Intra-oral examinations were conducted, and the thermographic data were analyzed to extract temperature values in the regions of interest (ROI). Point-biserial correlations and ROC curve analyses were performed to evaluate associations between temperature data and clinical findings, with a significance level of p<0.05. ResultsIntra-oral issues requiring treatment were found in 12 participants, with six reporting clinical pain. The overall mean temperature in the ROI was 33.5 ± 3.9°C, and significant temperature differences were found between the body and ROI temperatures. Correlations were observed between clinical problems and various temperature metrics, including the minimum and maximum ROI temperatures (rpb=-0.327, p=0.002 and rpb=-0.309, p=0.003). ROC analysis indicated that ROI temperature could predict the presence or absence of clinical problems, with AUC values ranging from 0.651 to 0.796 for different metrics. ConclusionThermographic facial imaging shows significant potential as a non-invasive tool for detecting oral health problems in vulnerable older adults. While promising, further research is essential to enhance image quality, streamline the technique, and incorporate AI for improved diagnostic accuracy and ease of use. Clinical SignificanceThis non-invasive, inexpensive technique is easy to perform, independent of patient compliance and, is promising to detect early oral problems in noncommunicative patients.

Conventional and machine learning-based analysis of age, body weight and body height significance in knot position-related thyrohyoid and cervical spine fractures in suicidal hangings.

The thyrohyoid complex and cervical spine fracture distribution patterns may reflect the knot position as the force distribution by the noose to different neck regions may vary depending on it. Recently, machine learning models (MLm) were used to classify knot position through these fractures. The contribution of aging on the fracture susceptibility is better demonstrated, but data on body weight (BW) and height (BH) significance on this is more doubtful and MLm did not consider them. A retrospectively obtained autopsy data on sex, age, BW, BH and distribution of greater hyoid bone horn (GHH), superior thyroid cartilage horn (STH), and cervical spine fractures in 368 suicidal hangings were analyzed by standard statistics to determine association of the anthropometrics (age, BW, and BH) with the fracture occurrence, and by machine learning algorithms to determine if body weight and height improved MLm classification of hanging cases with typical and atypical knot positions. In the sample, unilateral GHH fracture was significantly more common in atypical hangings, while isolated STH fractures were more common in typical hangings. Age was a predictor of GHH fractures and BW of STH fractures, but BW poorly correlated with their number. BH was not a predictor of any thyrohyoid fracture. On the ROC curve analysis, the MLm that considered BW and BH did not perform statistically better than MLm that did not consider them. The study indicates that body weight and height are of no detrimental value in assessing the thyrohyoid and cervical spine fracture patterns in suicidal hangings.

Habitat radiomics based on CT images to predict survival and immune status in hepatocellular carcinoma, a multi-cohort validation study.

Though several clinicopathological features are identified as prognostic indicators, potentially prognostic radiomic models are expected to preoperatively and noninvasively predict survival for HCC. Traditional radiomic models are lacking in a consideration for intratumoral regional heterogeneity. The study aimed to establish and validate the predictive power of multiple habitat radiomic models in predicting prognosis of hepatocellular carcinoma (HCC). A total of 232 HCC patients were retrospectively included, including a training/validation cohort and two external testing cohorts from 4 centers. For habitat radiomics, intratumoral habitat partitioning based on CT images was first performed by using Otsu thresholding method. Second, a total of 350 habitat radiomic models were constructed to select the optimal model. Then, both ROC curve analyses and Kaplan-Meier survival curve analyses were applied to assess the predictive performances. Ultimately, an immune status profiling was conducted based on bioinformatic analyses and multiplex immunohistochemistry (mIHC) assays to reveal the potential mechanisms. A total of 4 habitats were segmented, and the corresponding habitat radiomic models were constructed based on each habitat and an integration of all the four habitats. Generally, habitat radiomic models outperformed traditional radiomic models in stratifying prognosis for HCC. The habitat radiomic model based on the segmented habitat 4 involving decision tree (DT) screening and random forest (RF) classifier was identified as the optimal model with an AUCmean of 0.806. Distinct resting natural killer (NK) cell infiltrations significantly contributed to the prognosis stratification of HCC by the optimal habitat radiomic model. The habitat radiomic model based on CT images was potentially predictive of overall survival for HCC, with a superiority over the traditional radiomic model. The prognostic power of the habitat radiomic model was partly attributed to the distinct immune status captured in the CT images.

Using integrative bioinformatics approaches and machine-learning strategies to identify potential signatures for atrial fibrillation.

Atrial fibrillation (AF) is the most common tachyarrhythmia and seriously affects human health. Key targets of AF bioinformatics analysis can help to better understand the pathogenesis of AF and develop therapeutic targets. The left atrial appendage tissue of 20 patients with AF and 10 patients with sinus rhythm were collected for sequencing, and the expression data of the atrial tissue were obtained. Based on this, 2578 differentially expressed genes were obtained through differential analysis. Different express genes (DEGs) were functionally enriched on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), mainly focusing on neuroactive ligand-receptor interactions, neuronal cell body pathways, regulation of neurogenesis, and neuronal death, regulation of neuronal death, etc. Secondly, 14 significant module genes were obtained by analyzing the weighted gene co-expression network of DEGs. Next, LASSO and SVM analyzes were performed on the differential genes, and the results were in good agreement with the calibration curve of the nomogram model for predicting AF constructed by the weighted gene co-expression network key genes. The significant module genes obtained by the area under the ROC curve (AUC) analysis were analyzed. Through crossover, two key disease characteristic genes related to AF, HOXA2 and RND2, were screened out. RND2 was selected for further research, and qPCR verified the expression of RND2 in sinus rhythm patients and AF patients. Patients with sinus rhythm were significantly higher than those in AF patients. Our research indicates that RND2 is significantly associated with the onset of AF and can serve as a potential target for studying its pathogenesis.

Respiratory quotient as an early predictor of length of stay after cardiac surgery: A prospective observational study.

This study aimed to investigate the respiratory quotient (RQ) levels and its trend in the early postoperative period of patients with heart disease. Additionally, we explored factors influencing RQ and evaluated the predictive capabilities of RQ and lactic acid for various outcomes. In this prospective observational study, participants included were heart disease patients aged 18-80 years who underwent elective open-heart surgery and were subsequently admitted to the cardiothoracic surgery ICU post-operation. Indirect calorimetry (IC) measurements were conducted on patients dur-ing the first three days after surgery to assess their RQ levels. Clinical data, including personal information, postoperative characteristics, and duration of surgery, were documented based on the patient's medical history. In this study, 135 patients, of whom 57.04% were male, underwent a total of 247 IC measurements following cardiac surgery. On the first, second, and third days of admission to the ICU, the RQ values were 0.77±0.09, 0.80±0.07, and 0.78±0.05, respectively. The ROC curve analysis showed that on the first day of admission to the ICU, RQ was a better predictor of prolonged mechanical ventilation, LOS in ICU, and LOS in hospital compared to lactate level. However, on the second day of ICU admission, neither RQ nor lactate level could predict longer durations of mechanical ventilation, LOS in ICU, and LOS in hospital. RQ may serve as a potential predictor for LOS in patients after cardiac surgery.

Interaction of inflammatory factors related to pulmonary infection and TLR4/NF-κB signaling pathway in patients with spontaneous intracerebral hemorrhage.

To investigate the interaction of inflammatory factors related to pulmonary infection and the TLR4/NF-κB signaling pathway in patients with spontaneous intracerebral hemorrhage (ICH). A total of 325 critically ill ICH patients treated in our hospital from May 2021 to February 2024 were selected for this study. Based on whether the patient developed a pulmonary infection during treatment, they were divided into the infection group (n=86) and the non-infection group (n=239). The distribution characteristics of pathogens were observed, and changes in serum and defensin, hs-CRP, IL-4, TLR4 mRNA, and NF-κB mRNA were compared. Pearson correlation analysis was used to analyze the relationship between serum defensin, inflammatory factors, and the TLR4/NF-κB signaling pathway. A logistic regression model was used to construct a combined prediction model with defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, and NF-κB mRNA. ROC curves were drawn to analyze the area under the curve (AUC), sensitivity, and specificity of defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, NF-κB mRNA, and the six combined parameters for predicting pulmonary infection in critically ill ICH patients. In 86 ICH patients with pulmonary infection, 94 strains of pathogens were isolated, with 28 (29.79%) Gram-positive bacteria, 58 (61.70%) Gram-negative bacteria, and 8 (8.51%) fungi. The levels of defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, and NF-κB mRNA in the infection group were significantly higher than those in the non-infection group (P<0.05). Pearson correlation analysis showed that defensin, hs-CRP, IL-4, and HMGB1 were positively correlated with TLR4 mRNA and NF-κB mRNA (P<0.05). ROC curve analysis showed that the AUC values for defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, NF-κB mRNA, and the six combined parameters for predicting pulmonary infection were 0.789, 0.778, 0.690, 0.792, 0.741, 0.750, and 0.870, respectively. The main pathogens causing pulmonary infection in critically ill ICH patients are Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, and Streptococcus hemolyticus. Defensin, hs-CRP, IL-4, HMGB1, and other indicators are influenced by the TLR4/NF-κB signaling pathway in patients with secondary pulmonary infection.

Serum neurofilament light chain but not serum glial fibrillary acidic protein is a marker of early Huntington’s disease

BackgroundHuntington’s disease (HD) is caused by CAG trinucleotide expansion on chromosome 4, leading to mutant Huntingtin production. Premanifest carriers show no obvious clinical signs, and early symptoms progress slowly. Fluid biomarkers like neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), measurable in cerebrospinal fluid and serum (sNfL, sGFAP), offer potential predicting HD progression.ObjectiveTo assess the role of sGFAP and sNfL and clinical biomarkers in different disease stages and correlate with disease progression.MethodsHD mutation carriers were categorized into clinical stages according to their motor symptoms and functional capacities. The Unified HD Rating Scale, cognitive assessments and olfactory tests were used to characterize the patients clinically. Furthermore, sNfL and sGFAP levels were assessed.ResultsWe consecutively included 44 HD mutation carriers (13 premanifest HD (preHD), 18 in early (early HD) and 13 in advanced (advanced HD) disease stages) and 19 healthy controls (HC). Advanced HD patients performed worse on all clinical tasks and had higher sGFAP and sNfL levels compared to other groups (all p values < 0.05). We did not find difference in sGFAP levels between the preHD, early HD and HC group (all p values > 0.05). In contrast, sNfL levels differed significantly between preHD and early HD, and HC (all p values < 0.05). ROC curve analysis revealed that the AUC of sGFAP (0.970) exhibited superior discriminatory accuracy compared to sNfL (0.791) levels in separating advanced from early HD patients. By contrast, ROC curve analysis revealed that the AUC of sNFL (0.988) exhibited superior discriminatory accuracy compared to sGFAP (0.609) levels in separating all HD mutation carriers from HC.ConclusionsOur study indicates that sNfL can detect changes in very early and premanifest HD stages, whereas sGFAP showed differences in more advanced stages only.

Substantial Variability Exists in Reporting Clinically Significant Outcome Measure Thresholds for Arthroscopic Anterior Cruciate Ligament Reconstruction: A Systematic Review.

To systematically review the reporting of clinically significant outcome measure (CSO) thresholds and methods for calculating thresholds following anterior cruciate ligament (ACL) reconstruction. A systematic review of PubMed, Embase, and Web of Science databases was conducted to identify articles that met inclusion criteria from January 1, 2015, to July 7, 2024. Inclusion criteria included studies reporting CSO thresholds including minimal clinically important difference (MCID), substantial clinical benefit (SCB), or patient acceptable symptomatic state (PASS) for patients following ACL reconstruction with minimum 12-month follow-up. The MINORS criteria was used to assess study quality. Study demographics, patient-reported outcome measures (PROMs), CSO thresholds, and method of CSO calculation were collected. A total of 56 studies (n=52,292 patients) met the final inclusion criteria. Reported PROMs included International Knee Documentation Committee (IKDC) (n=35 studies), Knee Injury and Osteoarthritis Outcome score (KOOS) (n=33 studies), Tegner (n=20 studies) and Lysholm (n=19 studies) scores. The PASS was reported in 35 studies, MCID in 30, and SCB in 4. Among the studies that reported PASS, the most used threshold calculation was the ROC-Youden index (71.4%, n=25/35). In the studies reporting MCID, the most used threshold calculation was the 0.5 standard deviation (SD) of mean change method (36.7%, n=11/30). The most reported threshold calculation among the SCB studies was the ROC curve analysis (75%, n=3/4). In studies independently calculating CSOs, the most common methods were 0.5 standard deviations (SD) of mean change for MCID (50%, n=10/20), the ROC-Youden index for PASS (73.3%, n=11/15), and ROC curve analysis (75.0%, n=3/4) for SCB. Descriptions of anchor questions were reported in 22 studies (39.3%). Substantial variability exists in the reporting and calculation of MCID, SCB, and PASS for various PROMs following ACL reconstruction.

Circulating osteonectin predicts postural imbalance and cardiac dysfunction in heart failure.

Osteonectin, a secreted glycoprotein, plays a role in muscle-wasting disease. However, its role in chronic heart failure (CHF) -induced systemic inflammation and postural control is unknown. Here we aim to assess the potential association of soluble osteonectin with cardiac dysfunction and postural imbalance in CHF. The cardiac function, physical performance, including short physical performance battery (SPPB) for balance, handgrip strength (HGS), and the levels of plasma osteonectin and c-reactive protein (CRP) were assessed in controls (n = 56) and CHF patients (n = 286) presented with ischemic and non-ischemic CHF. CHF patients exhibited significantly lower HGS and postural balance accompanied by higher cardiac contractile dysfunction. Regardless of HF etiologies, the osteonectin and CRP levels were significantly higher in CHF patients vs. controls. The osteonectin exhibited a significant inverse correlation with left ventricular ejection fraction (LVEF) in both ischemic (r2 = 0.13, P < 0.0001) and non-ischemic (r2 = 0.18, P < 0.0001) CHF patients. Similarly, osteonectin has shown a strong negative correlation with cumulative SPPB score in both ischemic (r2 = 0.19, P < 0.0001) and non-ischemic (r2 = 0.22, P < 0.0001) patients. Further SPPB balance-based analysis demonstrated lower LVEF and markedly elevated osteonectin and CRP (P < 0.0001), particularly in patients with poor postural balance compared to those with relatively good balance. Importantly, osteonectin demonstrated significantly higher sensitivity and specificity for CHF diagnosis on ROC curve analysis. Taken together, higher osteonectin is associated with LV dysfunction and postural imbalance irrespective of CHF etiologies. It may serve as a biomarker for physical disability and contractile dysfunction in CHF patients.

Prevalence and predictive risk factors of hypertensive disorders in pregnant women at high risk for gestational diabetes. The PREeclampsia in DIabetiC gestaTION (PREDICTION) study.

Women with gestational diabetes (GDM) have increased risk of hypertensive disorders in pregnancy (HDP). However, knowledge remains limited for women with high-risk metabolic profiles, regardless of GDM diagnosis. This study aimed to evaluate the prevalence of HDP among women at high risk for GDM, while simultaneously identifying potential predictive clinical risk factors of HDP. Pregnant women who performed a 75-gr Oral Glucose Tolerance Test for the selective screening (based on pre-pregnancy risk factors) of GDM were prospectively enrolled (October 2019-June 2022). The development of HDPwas assessed. Logistic regression and ROC-curve analysis were used to identify predictive risk factors for HDP. Of the 398 women enrolled (53.5% with GDM), 30 (8%) developed HDP. Women developing HDP had more frequently a family history of type 2 diabetes, a personal history of GDM or preeclampsia, and showed higher pregestational BMI and first-trimester fasting plasma glucose. Moreover, at GDM screening, they had higher fasting and 1-hour glucose levels, and higher systolic and diastolic blood pressure. At logistic regression, systolic and diastolic blood pressure were the strongest risk factors for HDP. The risk increased for systolic blood pressure ≥ 127 mmHg (61% sensitivity, 86% specificity, PPV:27%, NPV:86%) and diastolic blood pressure ≥ 82 mmHg (57% sensitivity, 92% specificity, PPV:38%, NPV:96%). Women at high risk for GDM with poor metabolic profile have higher prevalence of HDP. Systolic and diastolic blood pressure at the time of GDM screening may identify women with higher risk of developing HDP, regardless of GDM diagnosis.

Identifying At-Risk Populations for Reoperations, Readmissions, and Interventions in MBSAQIP Using a Novel Inpatient Postoperative Care Metric.

Metabolic and bariatric surgery (MBS) is increasingly used for obesity and metabolic disease, with safety profiles showing it is among the safest major operations. The last 20 + years have noted significantly improved safety that has been accompanied by decreasing length of stay and select populations electing for outpatient surgery, leading to continued decreases in cost. Regardless, readmissions and complications still occur, requiring inpatient postoperative care (IP-POC). The current study aimed to identify and characterize at-risk populations for MBS-related IP-POC. The 2015-2021 MBSAQIP (n = 1,346,468 records) was used to extract 973,520 primary cases of laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch, and associated IP-POC. Conversions, pediatric cases, and < 30-day follow-up were excluded. IP-POC severity scores were calculated by summing readmissions (1 point), interventions (5 points), and reoperations (15 points). Risk factors associated with IP-POC were identified using zero-inflated Poisson models. GERD, COPD, smoking, and type of MBS procedure were significantly associated with increased IP-POC incidence and severity. Male sex was associated with increased severity but a lower likelihood of IP-POC, while Black and Hispanic race predicted increased IP-POC likelihood but not severity. ROC curve analysis identified IP-POC score thresholds of ≥ 6 and ≥ 10 as significantly associated with MACE (OR 2.4) and 30-day mortality (OR 4.7). The weighted IP-POC model demonstrated associations between preoperative characteristics and increased IP-POC likelihood and severity. These findings add to the current understanding of MBS patient care dynamics, and can be used to improve patient counseling, refine postoperative protocols, and optimize resource allocation.

Regional left ventricle strain outperforms global longitudinal strain in predicting late gadolinium enhancement in arrhythmogenic cardiomyopathy

Abstract Background Arrhythmogenic cardiomyopathy (AC) is a genetically determined heart muscle disease characterized by myocyte necrosis and consequent fibro-fatty replacement. The recognition of fibrosis is a relevant finding with important diagnostic and prognostic implications. Speckle tracking echocardiography (STE) may be more accurate than conventional echocardiography in detecting early myocardial alterations that need to be confirmed with the gold standard technique, cardiac magnetic resonance (CMR). Purpose The aim of our study is to evaluate if STE-derived strain analysis can predict the presence of fibrosis on CMR in the corresponding segment. Methods 86 patients with AC (including right/left dominant and biventricular forms) underwent advanced echocardiography with STE-derived strain analysis and CMR. Using a 17-segment Bull's-eye model, the cut-off value that best predicts the presence of gadolinium enhancement on CMR was determined for each wall segment using ROC curve analysis. Results The medium age was 45 (32-58) years, male gender was prevalent 71%. Among our patients, 44.1% had a biventricular form, 26.7% had a right-dominant form, 26.7% had a left-dominant form, and 2.3% had a borderline diagnosis. Regarding cardiovascular risk factors, 11.6% of patients had arterial hypertension, 15.1% had dyslipidemia, 2% had diabetes, 1% were smokers and 1% had coronary artery disease with previous percutaneous revascularization. The mean left ventricle (LV) ejection fraction (EF) was preserved 59% (54-64), while the medium LV global longitudinal strain (GLS) was slightly reduced, -18.2% (-20.1 to -15.2). A detailed analysis of regional wall strain was performed, and ROC curve analysis was used to determine a cut-off value for each segment to predict the presence of fibrosis on CMR in the corresponding segment, as shown in Table 1. Lower-than-average values demonstrated good accuracy in predicting the presence of fibrosis on CMR. Conclusions STE-strain analysis is a clinically accessible tool that enhances the sensitivity of echocardiography in detecting myocardial tissue alterations in AC, which would otherwise be identifiable only through CMR. Notably, even when GLS is within normal limits, regional strain sub-analysis can additionally reveal myocardial involvement. Table 1

Reclassification of patients with stage 2 or higher severe aortic valve stenosis based on left atrial reservoir strain

Abstract Introduction Survival following Transcatheter Aortic Valve Replacement (TAVR) is significantly influenced by the extent of extra-valvular cardiac damage at the time of the procedure. Génereux et al. introduced a staging system that classifies patients as stage 2 or higher if they have left atrial (LA) damage, defined as a Left Atrial Volume Index (LAVI) greater than 34mL/m². However, Left Atrial Strain (LAS) may serve as a more advanced method for assessing, LA damage and identifying high-risk patients. Aim This retrospective study aimed to evaluate the contribution of LAS in addition to LAVI in assessing the impairment of LA function in severe aortic valve stenosis (AS). Methods All patients with LAVI &amp;gt;34mL/m² who underwent TAVR between February 2021 and October 2023 were included in the study. Patients with poor quality echocardiographic images, moderate/severe mitral valve stenosis, mitral valve prosthesis, amyloidosis, or atrial fibrillation were excluded. Baseline echocardiographic images were analyzed offline to measure biplane LA volume, LAVI, LAS conduit (cd), LAS contractile (ct), and LAS reservoir (r). Additionally, left ventricular (LV) function was assessed by calculating ejection fraction (EF), global longitudinal strain (GLS), and myocardial work (MW) parameters. A ROC-curve analysis was performed to determine the LA parameter with the best predictive value, for stratification and survival analysis of patients. Results In total, 73 out of 176 AS patients were included in the analysis (39males, 83±5years, AVA 0.7±0.3cm2, MPG 47±15mmHg, LAVI 53±17mL/m²) . The majority of patients were in stage 2 while two were in stage 3 and three were in stage 4. During an average follow-up period of 419±287 days after TAVR, 11 patients died. No correlation was found between LA volume or LAVI and LV function parameters. However LAS parameters showed a significant correlation with EF and MW. Specifically, LASr had a significant correlation with EF (r=0.32), MW index(r=0.41), constructive work (CW, r=0.44), and MW efficiency (r=0.37). In the ROC-curve analysis, LASr demonstrated the highest predictive value (AUC 0.66). Patients with LASr values below the median (18.5%) exhibited significantly poorer long-term survival rates compared to those with LASr values above the median. Patient risk re-stratification based on the median LASr showed improved specificity compared to using LAVI&amp;gt; 34ml/m² as a risk marker (Figure 1). Furthermore, patients with low LASr values also displayed significantly worse values of GLS (-17±8 vs -14±4%, p=0.03), MW index (2598±686 vs 2054±677mmHg%, p=0.02), CW (3135±766 vs 2512±787mmHg%, p=0.02), and MW efficiency (93±5 vs 89±7%, p=0.03). Conclusion The identification of AS patients with LA damage (stage 2) due to LV dysfunction could be enhanced by implementing LASr as a more accurate parameter than LAVI. Additionally, LASr may help in identifying AS patients at risk following TAVR. Figure 1: Survival Analysis

Pulmonary artery acceleration time: a valid alternative when tricuspid regurgitation is missing

Abstract Background the latest guidelines from the European Society of Cardiology (ESC) on the diagnosis of pulmonary hypertension recommend the use of peak tricuspid regurgitation velocity (TRV) as an initial measure. However, in a significant proportion of patients this measurement is not feasible due to the absence of regurgitation or inadequate quality of the Doppler signal curve. Pulmonary artery acceleration time (PAAT), on the other hand, is a measurement that can be easily obtained in nearly all patients. Purpose the aim of our study is to analyse the relationship between PAAT and TRV and to evaluate its diagnostic accuracy for the TRV values established in the latest ESC guidelines (2.8m/s and 3.4m/s), determining appropriate cut-off points for this purpose. Methods a retrospective analysis was conducted on 1,255 consecutive transthoracic echocardiograms in which both TRV and PAAT were measured. Patients with pulmonary stenosis (peak velocity ≥ 2m/s) were excluded. The relationship between both variables was analyzed using different linear and non-linear models, choosing the one with the lowest degree of residuals. Diagnostic accuracy was assessed using the area under the curve (AUC) and sensitivity (Se) and specificity (Sp) values. Optimal cut-off points (OCP) were derived from ROC curve analysis. Results the mean age of the sample was 72.5±13.8 years, with 54% (683) being women and 63% (795) in sinus rhythm. Eighty six patients (7%) exhibited severe, massive or torrential tricuspid regurgitation. The mean TRV was 2.77±0.47m/s and the mean PAAT was 100.50±29.40ms. The mean TAPSE was 21.34±4.70mm, with 196 patients (16%) having systolic dysfunction (defined as TAPSE &amp;lt; 17mm). The relationship between TRV and PAAT fits a quadratic model (p for the quadratic term &amp;lt;0.001). The diagnostic accuracy of PAAT for both TRV cut-off points was good: TRV &amp;gt; 2.8m/s: AUC 0.78 [95% CI 0.76-0.80], OCP 93ms [Se 72.4%, Sp 71.8%]; TRV &amp;gt; 3.4m/s: AUC 0.80 [95% CI 0.78-0.82], OCP 85ms [Se 77.5%, Sp 70.6%]. Conclusions the relationship between TRV and PAAT follows a non-linear model. Cut-off points of 93ms and 85ms demonstrate good discriminatory power for identifying patients with TRV superior to 2.8m/s and 3.4m/s, respectively. Therefore, PAAT constitutes a reliable alternative for the initial echocardiographic assessment of the pulmonary hypertension probability in patients in whom TRV cannot be determined. Relationship PAAT/TRV

Evaluation of novel cardiovascular risk calculators in patients with rheumatoid arthritis

Abstract Background Patients with rheumatoid arthritis (RA) have a higher cardiovascular risk (CVR) compared to the general population contributing to a decreased life expectancy. Systematic and periodic assessment of CVR is recommended in all patients with RA. The newly developed PREVENTTM calculator was designed to estimate the absolute risk of cardiovascular disease and provides an estimate of atherosclerotic cardiovascular disease and heart failure. Purpose This study aimed to evaluate the sensitivity and specificity of the new PREVENTTM algorithm to identify CP in RA patients without prior CVD and to compare these results with other CVR algorithms. Methods We performed a cross-sectional study that included patients with RA aged 40 to 79 who fulfilled the 2010 ACR/EULAR Classification Criteria for RA. Patients with previous CVD, pregnancy, or overlap syndrome were excluded. A B-mode carotid ultrasound was performed on all patients. The presence of CP was defined as diffuse carotid intima-media thickness (cIMT) ³1.2 mm or focal thickness ³0.5 mm. The CVR was evaluated using Globorisk, HEARTS, QRISK3, ERS-RA, SCORE2, and PREVENTTM algorithms. The result was multiplied by 1.5 in algorithms where RA is not included as a variable, according to EULAR 2015/2016 recommendations. ROC curve analysis was performed to evaluate the different CVR algorithms' performance to identify CP. Youden index was calculated to select the optimum cutoff point and posteriorly calculate sensitivity, specificity, and predictive values. A p-value of £0.05 was considered statistically significant. Statistical analysis was performed with SPSS version 29.0 (IBM Corp, Armonk, NY, USA). Results A total of 261 patients with RA were included, mostly women (n=244, 93.5%), with a mean age of 56±9.3 years, and a median disease duration of 7.7 (3.0-14.7) years. Dyslipidemia was the most prevalent CVR factor (n=104, 39.8%). The prevalence of CP was 38.0%. According to the ROC curves, the Globorisk, HEARTS, and QRISK3 algorithms showed a higher area under the curve (AUC) than the other algorithms. The HEARTS and QRISK3 algorithms showed the highest positive likelihood ratios, showing rates of 1.87 and 1.84, respectively, to identify RA patients with CP (Figure 1). Conclusion Our study showed that Globorisk, HEARTS, and QRISK3 calculators presented the best diagnostic accuracy to detect CP in patients with RA. The novel CVR calculator PREVENTTM did not show better performance than older calculators in our population. Imaging studies evaluating coronary artery calcium and CP may offer better alternatives in high-risk populations like patients with RA.

Global longitudinal strain during stress echocardiography predicts major adverse cardiovascular events in patients with suspected chronic coronary syndrome.

Abstract Background Global longitudinal strain (GLS) is a robust prognostic marker in patients with coronary artery disease. The ABCDE stress echocardiography protocol has emerged as a novel tool for prognostic risk stratification beyond wall motion abnormalities. However, GLS during stress has not been incorporated in this protocol and its prognostic value remains to be confirmed. Purpose To assess the prognostic value of GLS during stress echocardiography to predict major adverse cardiovascular events in patients with suspected chronic coronary syndrome. Methods We recruited patients aged 18 years or older from 2017 to 2023 with suspected chronic coronary syndrome, who underwent clinically indicated stress echocardiography. Semiautomatic GLS of the LV was measured at rest and during stress. We included all types of stress: semi-supine bicycle, dobutamine, and dipyridamole. Logistic regression analysis was performed to assess the association between GLS and major adverse cardiovascular events (MACE). Results Eighty-one patients were included, age 61 (28-86) years, 52 were male (64 %), 60% had history of hypertension, 40% diabetes, 27% obesity and 14% previous acute coronary syndrome. Resting LVEF was 57% (± 11) and GLS 16% (± 4). After a mean follow up of 34 months, 24 patients (29%) presented MACE. Patients with MACE had lower LVEF 53 ± 13% vs 59% ± 10% (p&amp;lt;0.0328) and lower GLS 13.9± 4.5% vs 16.9 ± 3.9% (p&amp;lt;0.0029) at baseline. On univariate logistic regression analysis stress GLS was related to the occurrence of MACE, p=0.04. ROC curve analysis using Youden index identified that a cut off value of stress GLS &amp;lt;17% had a 47% sensitivity, 87% specificity. The survival analysis showed a 77.7% survival rate for those with GLS &amp;lt;17% than for those with GLS &amp;gt;17% (p=0.044) over 34 months of follow-up. Conclusion In patients with suspected chronic coronary syndrome undergoing stress echocardiography GLS during stress is a predictor for MACE. The survival of patients with less of 17% of GLS was significantly minor with a sensitivity of 47.37% and a specificity of 87.5%. ROC curve(Above) and Kaplan Meier Curve. Table 1.

Peak atrial longitudinal strain identifies patients with acute decompensated heart failure at high risk of cardiac death

Abstract Background Heart failure (HF) is an increasing health problem with high morbidity and mortality. Left atrial function has prognostic relevance in long-term survival of patients with HF. However, its prognostic value in patients with acute decompensated heart failure (ADHF) is less well studied. Objective The main objective of this study was to assess the association between PALS (peak atrial longitudinal strain) and cardiovascular (CV) death in patients ADHF. Methods A prospective single center study was performed. We enrolled patients admitted with ADHF according to the current European guidelines criteria. Clinical and biochemical data were collected. Echocardiography was performed during the first 24 hours of admission including quantification of left ventricular, right ventricular and left atrial function. Patients were followed up during hospitalization and at discharge. PALS was quantified by a single vendor equipment, using four and two chamber dedicated left atrial views and semi-automated software. The primary outcome was cardiovascular death at 3 years of follow-up. Variables were compared between patients with and without cardiovascular death. A ROC curve was constructed to define the best cut-off point, sensitivity, and specificity of PALS to predict the primary outcome. Results Sixty patients were included. The median age was 58 (24-90) years, 26% were female. Median NT-PRO BNP 5168 (186-70000) pg/mL, Creatinine clearance 70.6 ± 31.1 ml/min, hemoglobin 14.6 (1.5-19.3) g/dL. Left ventricular indexed end-diastolic volume 74.8 (26.8-181) ml/m2, left ventricular indexed end-systolic volume 51.4 (6.7-170.6) ml/m2, left ventricle ejection fraction 62.2 ± 13.6 %. Patients with cardiovascular death during follow-up, had lower LVEF 24 ± 8.3 vs 33.9 ± 13.8 % (p&amp;lt;0.033) and lower PALS 7.2 (4-14) vs (17 (3-39) %;(p&amp;lt; 0.002). In the ROC curve analysis, in the best-case scenario, an atrial strain value lower than 12% had a sensitivity of 72% and 90% of specificity for predicting cardiovascular death. Survival analysis demonstrated better survival in patients with PALS higher than 12%. Conclusions Left atrial strain is useful in patients with ADHF to identify patients at higher risk of cardiac death. According to our results, patients with PALS lower than 12% constitute a high-risk group in whom a closer follow-up and intensive treatment might be needed. Future studies are needed to confirm our findings. Survival according to PALS in ADHF

Association of serum and local GRP78 and CHOP expressions with disease progression in patients with non-traumatic osteonecrosis of femoral head

BackgroundThe endoplasmic reticulum stress (ER stress) has been involved in various musculoskeletal disorders including non-traumatic osteonecrosis of femoral head (NT-ONFH).ObjectiveThe current study aimed to investigate the association of glucose-regulated protein 78 (GRP78) as well as CCAAT/enhancer-binding protein homologous protein (CHOP) expressions in serum and femoral head (FH) tissues with NT-ONFH’s severity.MethodsWe enrolled NT-ONFH patients (n = 150) alongside healthy controls (HCs, n = 150). Meanwhile, 49 patients with femoral neck fracture (FNF) were also enrolled. Serum CHOP and GRP78 levels were determined through enzyme linked immunosorbent assay (ELISA). Local CHOP and GRP78 expressions were detected by immunohistochemistry, western blot, alongside real-time polymerase chain reaction (RT-PCR). Radiographic severity was assessed by FICAT grading system. The visual analogue scale (VAS) together with Harris hip score (HHS) were utilized to determine symptomatic severity.ResultsSerum CHOP and GRP78 levels were markedly increased in NT-ONFH patients than HCs. NT-ONFH patients at FICAT stage 4 showed significant higher serum CHOP and GRP78 levels in contrast with those at stage 3. Furthermore, patients at stage 3 demonstrated higher serum CHOP and GRP78 levels than those at stage 2. There was a positive correlation observed between the serum CHOP and GRP78 levels and the severity of the FICAT stages. A total of 42 ONFH patients at FICAT stage 3, 40 patients at FICAT stage 4, and 49 FNF patients received total hip replacement (THR). The mRNA and protein levels of CHOP and GRP78 were elevated in necrotic area compared to the non-necrotic area of ONFH patients and the FH tissues of FNF patients with statistical significance. The expression levels of CHOP and GRP78 within the local tissues were significantly elevated in patients at FICAT stage 4 as opposed to those at stage 3. Besides, ROC curve analysis indicated that serum and local CHOP and GRP78 expressions may act as indicators of disease progression. The levels of CHOP and GRP78, both in serum and at the local site, were in a positive correlation with VAS scores but an inverse relationship with HHS.ConclusionsSerum and local GRP78 as well as CHOP expressions were positively linked with disease progression in NT-ONFH patients. Potential therapeutics targeting ER stress related protein may serve as a method for alleviating NT-ONFH.

Atrial strain analysis predicts atrial arrhythmias recurrence following cavotricuspid isthmus ablation of typical atrial flutter

Abstract Background The evaluation of left atrial (LA) and right atrial (RA) function by two-dimensional speckle-tracking echocardiography has recently appeared as a valuable method to predict atrial arrhythmias (AA) recurrence after electrical cardioversion or transcatheter ablation. However, there are no similar studies performed in patients with typical atrial flutter (AFL). Aims The aim of our study is to assess the ability of RA and LA strain reservoir (RASr and LASr) to predict recurrence following cavotricuspid isthmus ablation (CTIA) for typical AFL. Methods Consecutive AFL patients who underwent CTIA at our hospital from January 2020 to May 2023 were retrospectively enrolled. Transthoracic echocardiography was performed within one month before CTIA and strain analysis was performed off-line. At follow-up, AA recurrence was recorded reviewing medical records. Results A total of 62 patients were analysed (mean age 64.8±13.2 years, 29% females). At a median follow up of 12.1 months (IQR: 7–18.4), AA recurrence occurred in 21 (33.8%). The study endpoint occurred mainly among females (p=0.021), patients who developed atrial fibrillation (AF) during CTIA and patients with lower RASr and LASr values (both p&amp;lt;0.001). At multivariable Cox regression analysis, only RASr and LASr remained independent predictors of AA recurrence (OR 0.904, 95% CI [0.831–0.984], p=0.02 and OR 0.919, 95% CI [0.852–0.992], p= 0.03, respectively). At ROC curve analysis, RASr and LASr showed similar and satisfactory ability to predict AA recurrence with optimal cut-off values of 16.8% and 17.7%, respectively. At survival analysis, RASr &amp;gt;16.8% and LASr &amp;gt;17.7% were associated with significantly higher freedom from AA (log rank p=0.001 and p=0.002, respectively). Conclusion In our study, lower values of both RASr and LASr resulted to be independent predictors of AA recurrence following CTIA for typical AFL. Therefore, pre-ablation atrial strain analysis may help in the detection of patients at higher risk of recurrence, which could benefit from closer follow up visits and prolonged antiarrhythmic therapy.