Receiver Operating Characteristic Research Articles

Imprecision and real-time clinical performance of a whole blood high sensitivity point of care troponin i: ready for prime time?

Abstract Introduction High sensitivity troponin (hs-cTn) measurement is central to rapid diagnostic algorithms in acute coronary syndrome (ACS). Point of care (POC) testing reduces turnaround time when compared to central lab (CL) testing. Currently there is very little data on the performance of POC hs-cTn assays in a clinical environment with non-expert operators. Method In a nested sub-study of a randomised controlled trial (RCT), patients with suspected ACS were randomised to either the ESC 0/1 or 0/3 hour algorithm. They underwent whole blood (WB) sampling for Siemens Atellica VTLi hs-cTnI POC (VTLi POC), CL hs-cTnI and CL hs-cTnT assays. This was for both initial and repeat samples. Assay imprecision of the VTLi POC assay was assessed by 2 runs of 10 tests with whole blood at 9 different troponin levels. 4 devices were used with samples stored at room temperature.Final diagnosis was adjudicated based on all relevant clinical and imaging data together with CL hs-cTnT as the diagnostic biomarker in clinical use (10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) and using the 4th universal definition of myocardial infarction (MI). Clinical performance was assessed using Receiver Operator Characteristics (ROC) curves. Results 2144 patients consented and had WB VTLi POC, CL hs-cTnI and CL hs-cTnT available. The index adjudicated type 1 MI rate was 6.1%. Assay imprecision of the VTLi POC assay demonstrated a 10% Coefficient of Variation (CV) at 9.8ng/l. This was >50% lower than the 99th centile of 23ng/l (average for males and females) (Figure 1). Clinical performance of the VTLi POC assay was acceptable and equivalent to CL hs-cTnT: Area Under Curve (AUC) 0.92 (0.89-0.96), 0.98 (0.96-0.99) and 0.93 (0.87-0.98) at presentation (Figure 2), 1 and 3 hours respectively. However, clinical performance was inferior to CL hs-cTnI: AUC 0.96 (0.95-0.98) and 0.96 (0.93-0.98) at presentation (p=0.0007) and 3 hours (p<0.0001) respectively. Conclusion The Siemens Altellica VTLi hs-cTnI POC assay has imprecision levels consistent with a high sensitivity troponin assay. It has acceptable clinical performance though inferior to the equivalent CL hs-cTnI. Further validation of this assay, particularly with optimised single sample rule-out, could facilitate its use in routine clinical practice.

Enhancement of the Mayo Clinic Genotype Predictor Score using Cardiac MRI

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiomyopathy typically transmitted in an autosomal dominant fashion. There is growing importance in identifying genetic test positive patients given its prognostic value. The Mayo HCM Genotype Predictor Score has been extensively validated for assessment of patient’s pre-test probability for genotype positive HCM and helps guide clinical decision-making based on clinical and echocardiographic variables. Herein, we evaluated the role of cardiac magnetic resonance (CMR) to enhance the genotype predictor score. Purpose Evaluate performance of the Mayo Clinic HCM Genotype Predictor Score using CMR variables, and develop an updated, CMR incorporated score. Methods Retrospective analysis was conducted on 175 unrelated HCM patients with at least 1 MRI and a HCM genetic testing seen at the Mayo Clinic between April 2004 and April 2018. Phenotyping information was obtained through review of electronic medical records. The original Mayo HCM Genotype Predictor Score was calculated using both echocardiography and clinical variables. An updated score was created incorporating CMR-specific variables. Diagnostic accuracy of the models was assessed thought Receiver Operating Characteristic (ROC) curves. Results Overall, 108 (62%) were males with a mean age at CMR of 51 ± 18 years. The yield of positive genetic test for the echocardiogram-derived Mayo HCM Genotype Predictor Score ranged from 38% for patients with -1 point to 100% for patients with 4 or 5 points. There was a significant incremental increase in diagnostic yield between score subgroups (p < 0.01) with an AUC of 0.659 (Figure 1A). Similar findings were observed using CMR variables (AUC of 0.697; Figure 1B). Univariate and multivariate analysis identified late gadolinium enhancement (LGE) as a strong predictor of a positive genetic test (OR 3.72; p=0.002), and it was added to the original score to create a new version. The Updated Mayo HCM Genotype Predictor Score predicted a positive genetic test ranging from 25% for patients with -1 point to 100% for patients with 5 or 6 points (p < 0.01). There was a significant increase in diagnostic accuracy when compared to the original score (AUC 0.724 vs 0.679; p=0.03; Figure 1C). Conclusion Using LGE, the updated CMR-based Mayo HCM Genotype Predictor score provides a simple and improved tool to aid in genetic counseling for HCM patients.

White Smoke in the Intermediate risk PE debate, could POPE be the solution?

Abstract Introduction In spite of a multitude of innovative therapeutic strategies emerging in the past decade, acute pulmonary embolism (PE) remains a potentially fatal disease. However, mortality varies significantly according to risk stratification, substantiating current recommendations to use reperfusion therapy only in hemodynamically unstable patients. There is an ongoing debate around whether hemodynamically stable patients showing signs of right ventricle dysfunction and myocardial injury (intermediate-high risk acute PE) may also benefit from reperfusion therapy. While the majority of patients in this category typically improve with anticoagulation alone, up to 10% may experience clinical deterioration. Aim We aimed to characterize the clinical in-hospital progression of patients with intermediate-risk PE and to evaluate the discriminative efficacy of PE scores in anticipating unfavorable clinical outcomes. Methods We conducted a retrospective observational study in patients admitted with the diagnosis of PE classified as intermediate risk in a tertiary center. Clinical, laboratory and ECG data were obtained. The BOVA score, the News score and the Pope score were evaluated. A composite endpoint of in-hospital mortality and use of reperfusion therapy due to hemodynamic deterioration was defined. Predictive abilities of these three scores were compared using area under the receiver operating characteristics (AUC-ROC) curve. Results From January 2019 to December 2020, a total of 166 patients were admitted with acute PE, classified as intermediate-risk, in our center. The mean age 71.9 ± 16.2 years and 57.2% were female. 71.1% of the pts showed bilateral PE in chest CT. The composite endpoint of in-hospital mortality and reperfusion therapy due to hemodynamic deterioration occurred in 9.8% of the pts. The median BOVA score was 3 (2-4), the median POPE score was 1 (0-2) and the median News score was 4 (2-6). The ROC curve analysis showed a significant higher discriminative power of POPE score compared to the other scores (AUC 0.856 95%CI 0.79–.92, p<0.001) (Fig1). Compared to patients with a POPE score 1, the composite endpoint was 4,6 times higher in patients with higher scores (OR 4.6 95%CI 1.63- 6914, p=0.029) (Fig2). Conclusion Despite classification as intermediate risk, these patients displayed a non-negligible in-hospital mortality rate. Close clinical monitoring is warranted in this group of pts and there is pressing need for an early identification of those who might benefit from more than just anticoagulation. In our population POPE score showed to be a simple and accurate tool in predicting those with an unfavorable evolution that could have benefitted from more advanced intervention.

Improving early mortality risk detection in light-chain cardiac amyloidosis patients with routine echocardiographic indicators and mayo staging

Abstract Background Light-chain cardiac amyloidosis (AL-CA) is a fatal cardiomyopathy caused by the deposition of monoclonal immunoglobulin light-chain in the cardiac fibers, conduction system, valves, and other parts of the heart. The Mayo 2004 staging system is widely used to assess the prognosis of AL-CA. Those in the highest-risk categories, Mayo 2004 stage IIIb, exhibit extremely poor responses to conventional treatment regimens, resulting in high early mortality rates. However, within the same stage, prognostic outcomes among patients can still vary significantly. Hence, a more detailed stratification of high-risk patients is crucial for pinpointing those at extreme risk. Objective To investigate whether conventional echocardiographic measurements can enhance the identification of high-risk patients with early mortality in AL-CA on the basis of existing risk stratification. Methods Continuous enrollment of patients diagnosed with AL-CA at our center from May 2020 to December 2022. Clinical data, echocardiography, and follow-up results of the patients were collected. Logistic regression analyses were used to identify risk factors for early mortality, with risk factor thresholds calculated using Receiver Operating Characteristic (ROC) curves. Kaplan-Meier survival analysis was employed to assess endpoint events. The diagnostic efficacy of the model was evaluated using the area under the ROC curve and the Integrated Discrimination Improvement (IDI). Results A total of 76 patients were included with an average age of 59±10 years. Among them, 51 were male (67.1%). The median follow-up duration was 10 months (ranging from 5 to 20 months). Early mortality, defined as death within 6 months, occurred in 20 patients (26.3%). Twenty-three patients were categorized under the Mayo 2004 stage IIIb (30.3%). The 6-month mortality rate for patients in the Mayo 2004 stage IIIb was 56.5%. The sensitivity of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity ratio divided left ventricular ejection fraction [(E/e’) /LVEF] in predicting early mortality in patients with AL-CA is 63%, and the specificity is 92%.When compared to the Mayo 2004 stage IIIb alone, (E/e')/LVEF≥0.5 combined with the Mayo 2004 stage IIIb had an area under the curve of 0.731 and 0.824, respectively, in the ROC curve. The IDI was 0.113 (95% CI: 0.013-0.213, P=0.026), representing an 11.3% enhancement in the predictive value of early mortality in AL-CA patients. Conclusion Routine echocardiography derived E/e' to LVEF ratio offered added prognostic value for early mortality beyond Mayo staging.Kaplan-Meier survival curve

Development of machine learning models for prediction of left ventricular systolic dysfunction in patients with isolated left ventricular dilation

Abstract Background/Introduction Isolated left ventricular dilation (ILVD), in the absence of concomitant LV systolic dysfunction, is a risk factor for new reduction in LV ejection fraction (LVEF) and adverse clinical outcomes. We assessed the performance of different machine learning (ML) models in predicting new reduction in LVEF in patients with ILVD. Methods A retrospective analysis of de-identified patient records in the Tempus Database with at least two transthoracic echocardiograms (TTE) conducted between January 2019 and December 2022 were retrospectively analyzed, with the follow up period ending in January 2023. Inclusion/exclusion criteria are shown in Figure 1A. Briefly, patients with ILVD were defined based on echocardiographic parameters as those with LVEF > 50% and LV end diastolic volume indexed (LVEDVi) > 62 mL/m2 for females and > 75 mL/m2 for males, without prior LVEF < 50% and/or grade 2/3 diastolic dysfunction. The endpoint was LVEF < 40% on future (≥90 days) TTE. Five hard voting ML models and one soft voting ensemble model were trained with data parsed from TTE reports (Figure 1B). Feature importance (SHAP) was calculated, and receiver operating characteristic (ROC) and Kaplan Meier curves evaluated the final model (Figure 1C-E). Results A total of 2,962 patients met the inclusion criteria. The median time from index to last TTE was 578 (IQR = 500) days. LVEF < 40% on follow up TTE was noted in 6% of patients (177 patients, median 478 days to endpoint, IQR = 535 days). Of the six models developed, the ensemble model had the highest ROC area under the curve (0.791, Figure 1D), precision (0.163), F1-score (0.266), and specificity (0.773). The ensemble model also had the lowest predicted prevalence (25.5%), although this was higher than the observed prevalence in the test set (5.7%). Patients predicted to develop LVEF < 40% had a 8.2x higher risk of developing LVEF < 40% within five years of index (p<0.001, Figure 1E). Feature importance showed that male gender, higher heart rate, lower LVEF at index TTE, higher LVEDVi, and lower tricuspid annular plane systolic excursion had the highest mean absolute impact on the model’s output probability (Figure 1C). Conclusion Using only data parsed from the index TTE, ensembling a model for the prediction of developing LVEF < 40% in patients with ILVD and without a history of LV diastolic or systolic dysfunction performed the best. Additional analyses including clinical variables such as comorbidities, symptoms, and medications may improve the model’s performance.

Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in general population: evidence from nhanes 1999-2010

Abstract Introduction Chronic inflammation is a recognized independent risk factor for cardiovascular disease (CVD), highlighting the need for reliable inflammatory indicators to predict CVD(1). As an inflammatory indicator which has been proved to have predictive value for the prognosis of CVDs, neutrophil percentage-to-albumin ratio (NPAR) has obtained increasing attention(2,3), but further research is needed to confirm the relationship with mortality in general population. Purpose To explore whether NPAR can serve as a predictive inflammatory indicator for CVD-cause and all-cause mortality in general population. Methods This prospective cohort study included 21317 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010. The baseline NPAR level was calculated as Neutrophil percentage (%) * 100/Albumin (g/dl). Data for CVD and all-cause mortality were acquired by linking the cohort database with the National Death Index through December 31, 2019.Weighted Kaplan–Meier curves with log-rank tests were conducted to access cumulative survival differences across different NPAR results. Restricted cubic spline analyses were employed to examine the nonlinear association. Multivariable Cox proportional hazards regression models were used to compute hazard ratios and 95% CIs. Receiver Operating Characteristic (ROC) curves were used to compare predictive value of NPAR with systemic immune inflammation index (SII) and neutrophils percent. Results In this cohort study, during 270014 person-years of follow-up, 4074 all-cause deaths and 1116 CVD-cause deaths were documented. We found significant associations between elevated NPAR and both CVD-cause and all-cause mortality in Kaplan–Meier curves (both P for log-rank test<0.001). Restricted cubic splines revealed non-linear associations between NPAR level and both CVD-cause (P=0.018 for nonlinearity) and all-cause mortality (P<0.001 for nonlinearity) (Figure 1A and 1B). After adjusting for confounding factors, participants in the highest NPAR tertile had a significantly increased risk of all-cause mortality (HR: 1.46, 95% CI: 1.33-1.61) and CVD-cause mortality (HR: 1.54, 95% CI: 1.32-1.80) compared to those in the lowest tertile, while no association was detected for individuals in the middle tertile (Figure 2). The effect of NPAR was consistent across most subgroups, with no significant interaction with most covariates except for high cholesterol (CVD-cause mortality: P=0.014, all-cause mortality: P=0.022). Further ROC analysis confirmed that NPAR had higher predictive value than neutrophil percent and SII. Conclusions Elevated NPAR level was significantly associated with an increased risk of all-cause and CVD-cause mortality in general population.Given its easy-to-calculate nature and high predictive value, NPAR index, with implications in public health, deserves greater attention in inflammatory assessment and cardiovascular prevention.Figure 1 Nonlinear associationFigure 2 Cox regression table

Novel parameters for micra transcatheter pacing system implantation on the right ventricular mid-septum

Abstract Background No procedural parameters for Micra transcatheter pacing system (Micra TPS) implantation on the right ventricular mid-septum have been established though it is encouraged for safety. Purpose We aimed to investigate procedural predictors for Micra TPS implantation on the ventricular mid-septum. Methods This is a single-center, retrospective and observational study. Eighty-two patients who underwent Micra TPS implantation were enrolled. The implantation sites of the ventricular septum were classified into basal, mid and apical-septum in the right anterior oblique 35° image. Predictors for mid-septal implantation were evaluated using univariable and multivariable logistic regression analysis which involved explanatory variables considered clinically important. The explanatory variables included the angle between the axis of a device cup of a delivery catheter and the tangent of the ventricular septum in the left anterior oblique 45° image (defined as angle θ). The diagnostic cut-off value of the significant predictor for mid-septal Micra implantation was assessed using receiver operating characteristic (ROC) curve analysis. Results Micra TPS was implanted on the ventricular mid-septum in 61 patients (74.4%), the apical-septum in 21 patients (25.6%), and the basal-septum in no patients. In univariable logistic regression analysis, each angle θ and α-loop shape appearance of a delivery catheter was significantly associated with mid-septal implantation (Odds ratio [OR], 1.1; 95% confidential interval [CI], 1.02-1.10; P=0.002, and OR, 4.6; 95% CI, 1.63-13.6; P=0.005, respectively). After multivariable adjustment, both angle θ and α-loop shape appearance were independently associated with mid-septal implantation (adjusted OR, 1.1; 95% CI, 1.01-1.09; P=0.010, and adjusted OR, 3.3; 95% CI, 1.01-11.4; P=0.048, respectively). Because no Micra TPS was implanted on the basal-septum, an ROC curve for binary outcome of mid-septal and apical-septal implantation was drawn. The ROC curve showed a cut-off value of angle θ for Micra TPS implantation on the ventricular mid-septum was 22° with high sensitivity and specificity at 80.0% and 70.0% (area under the curve= 0.781). Conclusion The angle θ ≧ 22°and the α-loop shape appearance of a delivery catheter may be useful predictors for Micra TPS implantation on the ventricular mid-septum.

Clinical prediction model of main adverse cardiovascular and cerebrovascular events for elderly patients with acute coronary syndrome

Abstract Background Age is an independent factor for adverse outcomes in acute coronary syndrome (ACS). With the accelerated aging process, there is an increasing incidence of ACS in the elderly; however, research on this population is underrepresented. Due to the unique presence of multiple diseases and organ changes in the elderly, specialized risk assessment tools are required. Purpose To explore the risk factors for poor prognosis of elderly patients with ACS and establishing a risk stratification tool. Methods The derivation cohort consisted of 1674 elderly ACS patients consecutively enrolled in a single center from January 2013 to December 2013. The validation cohort included 2333 elderly ACS patients consecutively enrolled in nine medical centers from January 2015 to May 2019. All patients were followed up for 2 years, and the study endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE). Model selection was performed using Cox regression and the Akaike Information Criterion (AIC) to construct the final risk assessment model. The performance of the predictive model was evaluated in the derivation and validation cohorts using the c-index, receiver operating characteristic (ROC) curves, and calibration curves. Results A total of 1,674 elderly ACS patients (70.97±4.68 years, 23.24% female) were included in the derivation cohort, and 210 cases (12.54%) of MACCE were recorded during the 2-year follow-up period. In the validation cohort, there were 2,333 elderly ACS patients (72.13±5.82 years, 35.83% female), with 364 cases (15.60%) of MACCE documented during the 2-year follow-up. Initially, 25 variables were preliminarily selected based on the results of univariate Cox regression and the clinical importance of these variables. Subsequently, these variables were included in a multivariable Cox model, and model selection was performed based on the AIC, resulting in the final selection of 10 variables (including age, cardiac insufficiency, current smoker, DAPT use, history of PCI or CABG, IABP use, number of lesions, residual SYNTAX score, preoperative HGB, and preoperative PLT). Then we developed and validated a nomogram to predict the 2-year MACCE in elderly ACS patients based on the assessment of 10 clinically easily obtainable variables during hospitalization. In both the derivation and validation cohorts, the nomogram demonstrated good discriminative ability (AUC of 0.723 and 0.699, c-index of 0.727 and 0.661, respectively) and calibration (calibration curves closely approximating the 45-degree diagonal line). The Kaplan-Meier analysis reveals significant differences in MACCE incidence rates between groups stratified by the median predicted probability (p<0.001). Conclusion Our study developed and validated a practical nomogram for predicting the 2-year risk of MACCE in elderly patients with ACS.

Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients

Abstract Background A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease. Methods This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT. Results A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT. Conclusion Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.

The intra-tumoral microbiome as a potential biomarker of response to external beam radiation therapy in cervical cancer

BackgroundWe aimed to determine the potential predictive value of the intra-tumoral microbiome as a marker of the response to external beam radiation therapy (EBRT) in cervical cancer (CC).MethodsA prospective longitudinal trial of 36 CC patients receiving pelvic radiotherapy was designed to investigate microbial characteristic signatures and diversity (alpha and beta) of multiple sites (tumor, vaginal, gut, urethral, and oral) in the superior response (SR) and inferior response (IR) groups of CC patients by 16S rRNA sequencing. Utilized the least absolute shrinkage and selection operator (LASSO) logistic regression method to analyze clinicopathological factors that potentially influenced the efficacy of EBRT. LEfSe analysis highlighted the microbiome features that best distinguished the categorized patient samples. Selected parameters were validated with Spearman correlation analysis, receiver operating characteristic (ROC) area under the curve (AUC) analysis and Kaplan-Meier survival analysis.ResultsFirstly, in our cohort, LASSO logistic regression analysis revealed no association between clinicopathological factors and EBRT efficacy. Subsequently, we employed 16S rRNA sequencing to compare microbiome differences across multiple sites and their correlations with major clinicopathological factors. We discovered that the intra-tumoral microbiome was independent of clinicopathologic features and represented the most direct and reliable reflection of the microbial differences between the SR and IR groups. We found lower alpha diversity in the tumor microbiome of SR group and identified the most relevant microbiome taxa (Bifidobacteriaceae, Beijerinckiaceae, and Orbaceae) associated with the efficacy of the response to EBRT in CC patients. We then conducted ROC analysis, finding that specific microbial taxa had an AUC of 0.831 (95% CI, 0.667–0.995), indicating the potential of these taxa as biomarkers for predicting EBRT efficacy. Kaplan-Meier survival analysis showed a better prognosis for patients with lower alpha diversity and higher relative abundance of Bifidobacteriaceae.ConclusionsOur data suggested that intra-tumoral specific microbiome taxa and lower alpha diversity may play an important role in the CC patient sensitivity to EBRT and offer novel potential biomarkers for predicting the response to EBRT efficacy.

CSTB, FABP4, IBP-1 and ST2 are strong predictors of mortality after transcatheter edge-to-edge mitral valve repair

Abstract Introduction Various clinical characteristics have emerged as prognostic factors in patients undergoing transcatheter edge-to-edge mitral valve repair (M-TEER). The use of biomarkers for outcome prediction has enormous potential. The goal of this study was to identify novel biomarkers linked with adverse events after M-TEER. Methods We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. Additionally, 94 follow-up samples were taken three months after M-TEER. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We analyzed differences in biomarker expression levels between patients that had died within one year after M-TEER and patients that had survived. Results 39 patients (16.3%) had died within one year after M-TEER. In these patients the most significantly upregulated biomarkers were NT-proBNP (expression 3.0-fold compared to survivors, p < 0.001), Cystatin B (CSTB; 2.0-fold, p < 0.001), fatty acid binding protein 4 (FABP4; 2.0-fold, p < 0.001), insulin-like growth factor-binding protein 1 (IBP-1; 1.9-fold, p < 0.001) and suppression of tumourigenicity 2 (ST2; 1.7-fold, p < 0.001). In non-survivors, expression levels of NT-proBNP (6.1-fold, p = 0.036), CSTB (3.2-fold, p = 0.050), FABP4 (3.7-fold, p = 0.037) and ST2 (2.1-fold, p = 0.017) were persistently elevated at the time of follow-up. Since its prognostic impact has already been described elsewhere, NT-proBNP was excluded from further analysis. Kaplan Meier analysis for 1-year mortality was carried out using tertiles of the respective biomarker expression levels. Mortality risk increased significantly with rising expression levels (CSTB: 3.4% in tertile 1, 12.2% in tertile 2, 37.9% in tertile 3; FABP4: 5.1%, 14.2% and 31.7%; IBP-1: 3.3%, 13.2% and 36.2%; ST2: 4.9%, 11.9% and 36.7%; p by log-rank-test < 0.001 for all biomarkers). Patients in which all 4 biomarkers were elevated to the highest tertile had an excessively high mortality risk of 52.9 vs. 13.5% (p by log-rank-test < 0.001). Receiver operating characteristic (ROC) analysis suggested higher predictive performances for mortality of all 4 biomarkers as compared to the EuroSCORE II (CSTB: area under the curve (AUC) 78.1%, 95% CI 70.7 – 85.5%; FABP4: AUC 71.6%, 95% CI 63.1 – 80.0%; IBP-1: AUC 73.9%, 95% CI 65.7 – 82.1%; ST2: AUC 76.2%, 95% CI 68.5 – 84.0%; EuroSCORE II: AUC 68.4%, 95% CI 59.3 – 77.5%). Conclusion This analysis has revealed novel biomarkers (CSTB, FABP4, IBP-1, ST2), which so far have not been characterized in M-TEER and suggests significant prognostic implications. Predictive performance of each of the respective biomarkers was superior to the most commonly used pre-operative risk stratification tool: the surgical EuroSCORE II. This hypothesis-generating study warrants further examination of these promising biomarkers.

AB-HFPEF score: A new and improved HFpEF prediction tool for the Indian patient

Abstract Background/Introduction Heart failure with preserved ejection fraction (HFpEF) remains underdiagnosed in low-middle income countries including India. The simple and validated H2FPEF score has largely replaced the diagnostic need for invasive right heart catheterization. The score has therapeutic implications by stratifying patients into low, intermediate and high-risk groups. The relevance of this score is yet to be ascertained in the Indian population. Purpose We hypothesized that the H2FPEF score may fall short in accurately predicting HFpEF in our population, thus warranting a new score. Methods We conducted a prospective observational study over one year at the out-patient department of a tertiary-care hospital in India. Patients presenting with clinical features of heart failure were screened and enrolled in the study. Demographic, clinical, laboratory and echocardiographic details were recorded by the principal investigator using an online data collection tool. Patients were stratified into ‘low risk’, ‘intermediate risk’ and ‘high risk’ probabilities, with respective cut-off values of 0-3, 4-6, and 7-9 using the point-based score, and <30%, 30-59%, and >60% via the continuous model of H2FPEF score. Pearson’s chi-square test identified significant risk factors that were purposed into a novel AB-HFPEF score. Cohen’s kappa correlation determined the degree of agreement in the risk stratifications of the H2FPEF and the AB-HFPEF score, using the continuous scoring model as the reference. Results Among the 189 patients screened, 137 were enrolled in the study. The baseline characteristics are recorded in Table 1. Pedal edema and uncontrolled hypertension were noteworthy risk factors. A novel AB-HFPEF score was subsequently designed and scored as follows: Age (> 60 years) - 1, BMI (> 30 kg/m2) - 2, uncontrolled Hypertension (>140/90 mmHg) - 1, Filling pressure (E/e' > 9) - 1, Pulmonary Artery Systolic Pressure (> 35 mmHg) - 1, pedal Edema - 1, atrial Fibrillation - 3. Receiver operating characteristics (ROC) curve analysis demonstrated an area under the ROC curve (AUC) of 0.85 (95%CI, 0.78 to 0.91) for ‘low risk’ strata and 0.87 (95%CI, 0.81 to 0.93) for ‘high risk’ strata. The optimal stratification was 0-2, 3-4, and 5-10 points for the ‘low risk’, ‘intermediate risk’, and ‘high risk’ respectively. There was a moderate agreement of the AB-HFPEF score with the reference score (κ = 0.48 (95% CI, 0.36 to 0.60), p < 0.001), while the point-based H2FPEF score had only a slight agreement (κ = 0.15 (95% CI, 0.05 to 0.25), p < 0.001), as illustrated in Figure 1. Conclusion(s) The novel AB-HFPEF score performs better risk stratification in Indian patients with HFpEF as compared to the point-based H2FPEF score. We hence propose the AB-HFPEF score as an instrument for tailored cardiology care in the Indian demographic, laying the cornerstone for larger validation and prognostication studies.Table 1:Baseline characteristicsFigure 1:Heat Map Illustration

Comparison of mortality scores performance in transcatheter aortic valve replacement: suiting up to percutaneous intervention

Abstract Introduction As transcatheter aortic valve replacement (TAVR) is increasingly relevant for patients with severe symptomatic aortic stenosis, having a reliable procedure specific risk-prediction tool is paramount to provide high-quality care. Surgical scores as the EuroScore II and the Society of Thoracic Surgeons (STS) score II have been widely used to identify patients with high surgical risk in whom percutaneous treatment might be more favorable. However, current literature lacks a consensual specific predictive model for short-term and mid-term prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). Purpose We aimed to access short and midterm (30 days and one year) mortality and to access the ability of a directly adapted score in estimating mortality in a real-world population. Methods We conducted a retrospective observational study in patients who implanted TAVR in a single center. Surgical mortality scores – EUROSCORE II and STS score II – and adapted score Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) transcatheter valve therapy (TVT) score were used to estimate mortality. Predictive abilities of these three scores were compared using area under the receiver operating characteristics (ROC) curve for 30-day and one year mortality. Results From January 2018 to December 2021, 416 patients were submitted to TAVR procedure in our center. The mean age was 83+-6 years old and 229 (55%) were female. 94% had hypertension, 80% dyslipidemia, 40% diabetes mellitus, 35% coronary artery disease, 32% chronic kidney disease. Mean ejection fraction was 56%. During a mean follow-up (FUP) of 816 ± 492 days, 30-day mortality was 1,7% and after 1 year mortality rate was 12,2% (higher than reported in PARTNER 3 trial, 8,5%). The Mean EuroSCORE was 3,4±3,2, mean STS-II 3,9±1,8 and mean value for STS/ACC-TVT score was 3,55±1,34. ROC curve analysis showed a significantly higher discriminative power of STS/ACC-TVT (AUC 0,749, 95% CI 0,681-0,818) compared with surgical scores (p=0,001) – figure 1. We also divided population into quartiles and compared the mortality rate at 30 days and 1 year in each quartile using either STSII or STS/ACC-TVT; As can be seen in figure 2, mortality rates correlated better with the STS/ACC-TVT score than with the STS score. Conclusion A score adapted to a TAVI population showed better predictive capacity than traditional surgical scores. Less preponderance of previous surgical status, relevance of access site and more adapted weight of age might explain the best performance of STS/ACC-TVT score. Surgical scores are helpful in choosing treatment option, but adapted scores are better to predict pos-TAVR mortality.

Mixed venous to arterial pCO2-gap is poorly correlated to cardiac index in 1526 pulmonary artery catheter monitored critically ill patients

Abstract Background The CO2 gap is the difference between mixed venous and arterial CO2, and can be estimated by the difference in partial pressure in CO2 (Pv-aCO2 or ∆PCO2). ∆PCO2 is affected by cardiac output (CO), CO2 production and solubility. The central venous-to-arterial CO2 gap has been proposed as a less invasive surrogate for P(v-a)CO2 and has been investigated as a measure of adequacy of resuscitation, and to guide sepsis management. Nevertheless, the CO2-gap as determinant of CO has never been thoroughly investigated in large cohort of critically ill ICU-patients. This study aims to investigate the relationship between ∆PCO2 and cardiac index (CI) in a retrospective cohort of critically ill patients in a large quaternary cardiothoracic intensive care unit. Methods Over 62 months, pulmonary artery catheter monitored critically ill patients were identified and their case files reviewed in retrospect. Extracorporeal membrane oxygenation (ECMO) patients were excluded. P(v-a)CO2 measurements were defined as mixed venous and arterial pCO2 measurements drawn simultaneously or within maximum 30 minutes together with PA-measurements. Correlation coefficients were calculated between P(v-a)CO2 and CI, serum lactate, mixed venous saturations (SvO2), cardiac power index (CPI), inotropic score (IS), central venous pressure (CVP) and minute expiratory volume (MV)(Table 1). We used receiver operator characteristic (ROC) curves to assess the diagnostic performance of P(v-a)CO2 as a surrogate for CI lower than 2,2L/min/m2. Multivariate linear regression analysis was performed with P(v-a)CO2 as an dependent variable. Results 4414 P(v-a)CO2 measurements were identified from 1526 patients. Median P(v-a)CO2 was 0,86 kPa (0,66-1,1) or 6.45 mmHg (4.95-8.25), and mean CI was 2.7l/min/m2 (2.2-3.2). Correlation coefficients of P(v-a)CO2 with the other variables remained poor (> 0,35). The area under the ROC curve for P(v-a)CO2 as a predictor of CI<2.2l/min/m2 was 0.65, p<0.0001 (Fig. 1B). A value of P(v-a)CO2 > 6.9 mmHg was found to have the highest sensitivity and specificity, with a poor performance of 61.21% sensitivity and 62.73% specificity. Conclusion This large retrospective study in 1526 critically ill cardiac ICU-patients did not demonstrate a strong relationship between P(v-a)CO2 and CI, nor with any other hemodynamic variable found in the ICU patient cohort studied (Table 1). This raises scepticism regarding the efficacy of P(v-a)CO2 as a physiological goal in guiding resuscitation and management of this precarious patient group. Therefore, we argue that the PA-catheter remains the cornerstone in assessing critically ill (cardiothoracic) ICU patients.

VERMONT non-optimised: can baseline diagnostic catheter images be used to measure angiography based CAAS-vFFR?

Abstract Background We have previously reported strong diagnostic accuracy and validity of angiography-based vessel Fractional Flow Reserve (CAAS-vFFR) compared to conventional wire based Fractional Flow Reserve (FFR)(1). The CAAS-vFFR system requires at least two additional optimised angiographic cine images taken after intracoronary glyceryl trinitrate administration, separated by ≥ 30 degrees at a frame-rate of ≥ 15 frames/seconds with minimal overlap and foreshortening, no table movement and adequate contrast opacification. At present, there is a paucity of data regarding the validity of using baseline non-optimised diagnostic cine images in the assessment of CAAS-vFFR. Purpose To assess the concordance and validity of using baseline non-optimised diagnostic cine images in measuring angiography based CAAS-vFFR. Methods We conducted an investigator-initiated, single centre, blinded, prospective observational study performing wire based FFR and CAAS-vFFR conducted simultaneously in patients undergoing routine wire-based FFR for intermediate coronary stenoses. All eligible patients had baseline diagnostic and optimised guide-catheter based angiographic images acquired. Results 195 consecutive patients with 205 lesions were recruited over 19 months; 56 (27.3%) lesions were excluded due to inadequate baseline cine angiogram images (Picture 1). 102 (68.5%) had stable symptoms and 107 (71.8%) were male. The median age was 65.0 years (interquartile range 59.0 – 73.0) and mean body-mass-index was 29.2 kg/m2 (± 5.8). There were 117 (78.5%) lesions in the left anterior descending artery/diagonal branches, 20 (13.4%) in the right coronary artery and 12 (8.1%) in the left circumflex artery/marginal branches. There were 93 (62.4%) diffuse (≥ 20 cm), 23 (15.4%) bifurcation and 15 (10.1%) ostial lesions. The mean optimised vFFR and non-optimised vFFR were 0.80 (± 0.1) and 0.79 (± 0.1) respectively with a Pearson correlation of 0.87 (p<0.001). Overall, 52 lesions (34.9%) and 73 lesions (49.0%) had a wire-based FFR and non-optimised vFFR value of ≤ 80 respectively. The mean wire-based FFR and non-optimised vFFR were 0.82 (± 0.1) and 0.79 (± 0.1) respectively. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic accuracy of non-optimised vFFR in predicting a wire based FFR of ≤ 80 (AUC 0.91; 95% CI; 0.87-0.96) (Picture 2). Baseline non-optimised diagnostic vFFR images produced a sensitivity of 94.2%, specificity of 75.3%, positive-predictive-value (PPV) of 67.1% and negative-predictive-value (NPV) of 96.1% compared with wire-based FFR. Conclusions CAAS-vFFR derived values from baseline non-optimised diagnostic cine images were strongly concordant with those derived from optimised images and displayed a high sensitivity and NPV compared to wire-based FFR. This reflects the potential for CAAS-vFFR to have broader clinical applications and be utilised as a retrospective screening tool for intermediate lesions.Excluded baseline angiogram lesionsROC Curve

Cut-off values for estimated cardiorespiratory fitness in terms of physical functioning among middle-aged to older adults.

Cardiorespiratory fitness is linked to various health outcomes. This study aimed to establish cut-off values for estimated cardiorespiratory fitness associated with poor physical functioning in middle-aged to older adults. A total of 2638 participants (1083 males), aged 40-69 years, performed a 6-min walking test (6MWT) to estimate cardiorespiratory fitness (VO<inf>2max)</inf> and completed a health-related questionnaire. Physical functioning was assessed using four outcomes: perceived health, perceived fitness, difficulties in 2-km walking, and difficulties in climbing several stairs. Receiver operator characteristics (ROC) curves were used to determine cut-off values for estimated VO<inf>2max</inf> and 6MWT distance linked to poor physical functioning based on the four outcomes. Analyses were done separately for males and females, and for 40- to 49-, 50- to 59-, and 60- to 69-year-old groups. Multinomial regression was used to analyze differences between fitness thirds in outcome variables. ROC analyses were significant for all outcomes (AUC 0.686-0.834, P<0.001). In the total group, cut-off values for estimated VO<inf>2max</inf> were 29.9-30.2 mL/kg/min, and for walking distance, 588.0-599.5 m. Cut-off values decreased with age, and mean differences between males and females were 3.3 mL/kg/min and 33 m. All cut-off values were within ±1.3 mL/kg/min of the lower fitness tertile. The odds ratios of having poor physical functioning in the middle and high fitness thirds were less than 0.50 compared to low fitness third. VO<inf>2max</inf> of 30 mL/kg/min and 600-m walking distance seemed reasonable cut-off values for poor physical functioning. Exceeding the currently proposed thresholds is a desirable goal to avoid consequences of insufficient fitness.

Prognostic role of inflammatory status in type 2 myocardial infarction

Abstract Background there is a wealth of evidence on the importance of inflammatory status in destabilization of chronic artery plaques that led to acute myocardial infarction. However, its role in the setting of type 2 myocardial infarction (T2MI) is not yet specifically known. Purpose We investigated prognostic role of inflammatory parameters in T2MI. Methods We consecutively enrolled 461 T2MI patients from January 2017 to June 2021. T2MI was defined according to the fourth Universal Definition of Myocardial Infarction. We divided the overall population in patients who experience major cardiovascular events (MACE), n=166, and in those who do not (n=277). Receiver operating characteristic (ROC) curve analysis were used to assess the diagnostic accuracy of various inflammatory parameters for predict MACE occurrence during long term follow-up. We divided patients into two groups (high and low inflammatory burden) based on the value associated with the highest Youen index. Cox proportional hazards regression models were constructed to estimate the independent role of these parameters in predict MACE. Results We found that patients who experienced MACE had a higher level of inflammatory parameters, in particular hs-CRP (2.21±3.7 vs 1.48 ±3.5, p&amp;lt;0.001) and platelet-to-neutrophil ratio (3.72 ±1.52 vs 3.7±1.43, p=0.02). Using ROC analysis, the area under the curve (AUC) of hs-CRP was the largest among all inflammatory parameters and the optimal threshold, according to Youden’s index, was found to be 1.2 mg/dL. MACE-free survival curves, comparing groups with low hs-CRP (&amp;lt; 1.2 mg/dL) and high hs-CRP (≥ 1.2 mg/dL), showed that high hs-CRP was associated with a worse prognosis (p&amp;lt;0.001). At Cox regression models, hs-CRP value ≥1.2 mg/dL was independently associated with MACE (p=0.01) together with diabetes (p=0.006), chronic obstructive pulmonary disease (p=0.006), previous stroke (p=0.001) and older age (p&amp;lt;0.001). Conclusion T2MI patients who experienced MACE exhibited higher levels of inflammatory parameters. Patients with hs-CRP levels ≥1.2 mg/dL had a worse prognosis, independently predicting MACE. These findings underscore the potential utility of hs-CRP as a prognostic biomarker in risk-stratifying patients with T2MI and highlight the importance of addressing inflammatory status in optimizing patient management and improving outcomes.

Echocardiographic left atrial stiffness index predicts high left ventricular filling pressures in patients with acute heart failure: an observational study.

In acute heart failure (AHF) patients, non-invasive estimation of left ventricular filling pressures (LVFPs) appears crucial to guide management. Although poorly investigated, left atrial (LA) mechanics play a pivotal role in this setting. This report sought to assess the correlation of echocardiographic LA stiffness index with invasive LVFPs and its diagnostic accuracy as compared to other parameters used in clinical practice. In this observational, prospective study, 104 patients with suspected acute coronary syndrome and signs/symptoms of AHF were enrolled. Available invasive estimation of LVFPs was required. Comprehensive echocardiography was performed for all patients, including LA reservoir strain (LARS). LA stiffness index was derived by speckle-tracking analysis and Tissue Doppler imaging as early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e']/LARS. Invasively measured LVFPs showed a strong correlation with LA stiffness index (Spearman ρ = 0.773, p < 0.0001), as well as with LARS and E/e'. Receiver operating characteristic (ROC) curve analysis was used to demonstrate better accuracy performed by LA stiffness index than average E/e', LA volume or LARS alone, in predicting high LVFPs. Guideline-recommended assessment of diastolic function was finally compared to LARS and LA stiffness index performances in an independent population group; we were hence able to obtain a LA stiffness threshold of 0.48 with a positive predictive value of 91.7% and a negative predictive value of 88.9% in identifying patients with high LVFPs. For the first time, diagnostic performance of LA stiffness index has been investigated in a heterogeneous AHF population, providing correlations with invasively measured LVFPs and comparisons with established diastolic function metrics.

The admission inflammatory biomarkers profile of elderly hip fractures and its association with one-year walking independence and mortality: a prospective study.

Immune response plays an important role in the regulation of elderly hip fracture. This study aims to analyze the relationship between systemic inflammatory markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) and mortality and walking independence, providing valuable references for the postoperative management of geriatric hip fracture. A retrospective analysis of prospective data on elderly patients who have undergone hip surgery and have been followed for at least one year. The receiver operating characteristic (ROC) curves and the optimum cutoff value were calculated. Univariate analysis and multivariate logistic regression analysis were used to identify the associations between admission four systemic inflammatory markers and one-year mortality and locomotion recovery. During the study period, respiratory disease was the most common cause of death, followed by cardiovascular disease. Multivariate analysis identified NLR (OR, 1.13; 95%CI: 1.09-1.17), SIRI(OR, 1.18; 95%CI: 1.08-1.28) and advanced age (OR, 1.06; 95%CI: 1.01-1.11) as independent risk factors for one-year mortality. In addition, 89 (rate, 31.8%) survivors had poor walking independence within one year. NLR (OR, 1.37; 95%CI: 1.26-1.50), SII(OR, 1.00; 95%CI: 1.001-1.003), SIRI(OR, 1.36; 95%CI: 1.18-1.57) and advanced age (OR, 1.08; 95%CI: 1.02-1.13) were associated with postoperative locomotion recovery. In summary, admission NLR and SIRI are correlated with a high risk of one-year walking independence and mortality, providing a basis for the clinical management of geriatric hip fractures.

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.