Univariate Cox Regression Research Articles

Comparison of different non-invasive estimates of right ventriculo-arterial coupling as outcome predictors in dilated cardiomyopathy

Abstract Right ventriculo-arterial coupling (RVAC) has emerged as an outcome predictor in pulmonary hypertension, but its role in left-sided HF remains to be clarified. Different non-invasive estimates for RVAC have been proposed, but a direct comparison of their prognostic ability is lacking. We sought to evaluate RVAC non-invasively using five different methods in a cohort of patients with dilated cardiomyopathy (DCM) and to assess their prognostic role. We enrolled 121 consecutive patients with non-ischemic DCM in sinus rhythm, who underwent comprehensive echocardiography, including speckle-tracking and 3D analysis. They were prospectively followed for 19±11 months for a composite endpoint of death, nonfatal cardiac arrest and hospitalization. RVAC was measured using five non-invasive estimates: (1) as the tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio; (2) as the right ventricular (RV) global longitudinal strain (RV-GLS)/PASP ratio; (3) as the longitudinal strain of the RV free wall (LS-RVFW)/PASP ratio; (4) as the 3D RV ejection fraction (RVEF)/PASP ratio; and (5) as the 3D RV stroke volume (SV)/3D RV end-systolic volume (ESV) ratio. Mean age in the study cohort was 59±14 years and the majority (74%) were men. 55 patients (46%) reached the endpoint: there were 27 deaths, 5 nonfatal cardiac arrests and 23 readmissions for heart failure. Patients with adverse outcome had lower TAPSE/PASP (0.42±0.23 vs. 0.62±0.33, p<0.001), lower RVEF/PASP (0.96±0.49 vs. 1.47±0.67, p<0.001), lower RV SV/ESV (0.57±0.20 vs. 0.93±0.29, p<0.001) and higher RV-GLS/PASP (-0.25±0.20 vs. -0.38±0.23, p=0.002) and LS-RVFW/PASP (-0.28±0.30 vs. -0.51±0.33, p<0.001), reflecting greater ventriculo-vascular decoupling. In univariate Cox regression, all three RVAC indices were outcome predictors: HR=0.09 [95% CI, 0.02-0.37], p=0.001 for TAPSE/PASP, HR=13.67 [95% CI, 2.77-67.48], p=0.001 for RV-GLS/PASP, HR=8.72 [95% CI, 3.24-23.45], p<0.001 for LS-RVFW/PASP, HR=0.27 [95% CI, 0.14-0.50], p<0.001 for RVEF/PASP, HR=0.004 [95% CI, 0.001-0.019], p<0.001 for RV SV/ESV. In ROC analysis, the SV/ESV ratio had the highest AUC (AUC=0.88, p<0.001), a value lower than 0.74 having 86% sensitivity and 77% specificity for event prediction. After adjustment for age, NYHA class, left ventricular ejection fraction, and maximal left atrial volume, all coupling indices remained independent predictors of outcome: HR=1.90 [95% CI, 1.01-3.57], p=0.047 for TAPSE/PASP, HR=2.15 [95% CI, 1.17-3.96], p=0.01 for RV-GLS/PASP, HR=2.48 [95% CI, 1.34-4.60], p=0.004 for LS-RVFW/PASP, HR=3.19 [95% CI, 1.19-8.52], p=0.02 for RVEF/PASP, HR=7.50 [95% CI, 3.47-16.22], p<0.001 for RV SV/ESV. In DCM, RVAC is significantly more impaired in patients with major adverse events. Non-invasive RVAC was an independent predictor of adverse outcome irrespective of the formula used for estimation, but 3D RV SV/ESV ratio had the greatest prognostic power.

Prognostic value of circulating glypican-4 in patients with chronic heart failure with reduced ejection fraction

Abstract Background Chronic heart failure is one of the leading causes of hospitalization and mortality worldwide, with an ever-increasing prevalence. Glypican-4 (GPC4) is a cell surface protein part of the endothelial glycocalyx which is actively released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. The current literature on the association between circulating GPC4 and heart failure is limited and its prognostic value on top of established risk markers in chronic heart failure is unknown. Purpose In the present study, we aim to investigate the prognostic value of circulating GPC4 on clinical outcomes in a contemporary cohort of patients with stable chronic heart failure with reduced ejection fraction (HFrEF). Methods Symptomatic outpatients with stable chronic HFrEF were consecutively enrolled in a prospective cohort study. Circulating serum GPC4 levels were assessed using an enzyme-linked immunosorbent at baseline. Patient outcomes were retrieved from medical and health insurance records. Results We enrolled 205 patients with a median (interquartile range) age of 66 (59-74) years, with 22% females. Median left ventricular ejection fraction (LVEF) was 37 (30-43)%, median estimated glomerular filtration rate (eGFR) was 64 (48-80) ml/min/1,73 m2, median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 964 (336-2173) pg/ml, median interleukin 6 (IL6) was 4.7 (3.2-7.9) pg/ml, and median GPC4 was 1553 (1034-1950) pg/ml. During a median follow-up of 4.7 (4.0-5.3) years, 46 patients (22%) were hospitalized due to worsening heart failure (WHF), 18 patients (9%) died of cardiovascular (CV) cause, and 58 patients (28%) died of any cause. In univariate Cox-regression, serum GPC4 levels predicted WHF (HR 1.57, 95%CI 1.29-1.92, p<0.001), CV death (HR 2.07, 95%CI 1.56-2.74, p<0.001), and all-cause mortality (HR 1.93, 95%CI 1.59-2.34, p<0.001). The association between serum GPC4 levels and both, CV death (HR 1.69, 95%CI 1.04-2.86, p=0.048) and all-cause mortality (HR 1.56, 95%CI 1.14-2.14, p=0.006) remained significant in a multivariable Cox-regression model adjusted for age, sex, eGFR, IL6, NT-proBNP, and LVEF. Conclusion In patients with stable chronic HFrEF, circulating GPC4 is significantly associated with cardiovascular outcome and is an independent predictor of all-cause mortality. The potential prognostic value in clinical routine of GPC4 should be addressed in prospective studies.

The impact of QRS complex fragmentation status before and after cardiac resynchronization therapy with defibrillator implantation: Is it a predictor of arrhythmic events?

Abstract Introduction Cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) has demonstrated efficacy in reducing mortality, hospitalization for heart failure (HF), and sudden cardiac death among subgroups of patients with HF with reduced ejection fraction (HFrEF). However, this population is highly heterogeneous, necessitating risk stratification. Several clinical findings, including QRS complex fragmentation (QRSf), have been identified as potential prognostic factors for arrhythmic risk. Nonetheless, evidence supporting the prognostic significance of QRSf in patients undergoing CRT-D remains limited. Purpose The aim of this study is to assess whether alterations in QRSf status, before and after CRT-D implantation, can predict arrhythmic events (AE) in patients with HFrEF. Methods This study included consecutive patients underwent CRT-D implantation at our center from October 2009 to December 2022. Demographic, clinical, electrocardiographic and echocardiographic data were obtained from electronic medical records and telephone interviews. QRSf was defined by the presence of various RSR′ patterns, including additional R waves (R′) or notching of the R and S wave in two contiguous leads corresponding to a primary coronary artery territory on a 12-lead electrocardiogram conducted before and after CRT-D implantation. An AE was characterized by appropriate ICD therapy (antitachycardia pacing or shock) for a ventricular arrhythmia or sustained ventricular arrhythmia without the need for ICD therapy. Results A total of 176 patients were included (mean age 69.9 ± 9.6 years with 80.6% male). Ischemic etiology accounted for 54.6% of cases of LV systolic dysfunction, with a mean baseline LVEF of 23.6%. CRT-D was indicated as secondary prevention in 18 patients. At baseline, 114 patients (64.8%) presented QRSf. Following CRT implantation, 17 patients (9.8%) without previous QRSf developed QRSf, while 26 patients (14.9%) resolved QRSf. The median follow-up was 43.6 months (interquartile range 19.5-81.1). During follow-up, 90 patients died and 29 AE occurred (16.5%). Among these, 23 patients had QRSf before and after CRT, whereas 6 AE occurred in patients without QRSf. Multivariate survival analysis using Cox regression demonstrated that the presence of QRSf before and after CRT-D was an independent predictor of AE (HR 3.56; 95% CI 1.00-12.70). Univariate and multivariate Cox regression analyses are presented in Table 1. Kaplan-Meier curves for AE in relation to QRSf status before and after CRT-D are illustrated in Figure 1. Conclusions Our findings suggest that the presence of QRSf and its persistence following CRT-D implantation appears to be an independent predictor of AE after CRT-D implantation in patients with HFrEF. Therefore, these patients would benefit from closer monitoring as they exhibit a heightened risk of arrhythmic events. Nevertheless, further research is warranted to validate these results.Table 1.Cox Regression Analysis.

Impact of QRS complex fragmentation on all-cause mortality before and after cardiac resynchronization therapy

Abstract Introduction Cardiac resynchronization therapy (CRT) have demonstrated to reduce all-cause mortality in selected patients with HFrEF. However, there is still a high rate of non-responders, so risk stratification is crucial. Fragmentation of the QRS complex (QRSf) has been suggested as a valuable prognostic factor in different cardiac diseases, but the evidence in patients undergoing CRT is controversial and limited. Purpose To evaluate if changes in QRSf status before and after CRT implantation has a prognostic role in patients undergoing CRT in terms all-cause mortality. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. QRSf complex was defined by the presence of different RSR′ patterns including additional R-waves (R′) and notches of the R-wave and S-wave in two contiguous leads corresponding to a main coronary artery territory in a 12-lead electrocardiogram performed before and after CRT. Results A total of 244 patients (mean age 71.8 ± 9.8 years, 79.5% male) were included. The etiology of LV systolic disfunction was ischemic in 50.0%. Mean LVEF before implantation was 25 ± 9%. A CRT-D was implanted in 176 patients (72.2%). The mean width of the paced QRS was 141 ± 23 ms. At baseline, 150 patients had a QRSf. After CRT implantation, 69 (28.4%) patients experimented a change in QRSf status: 29 patients (11.9%) without prior QRSf developed QRSf, whereas 40 patients (16.5%) resolved QRSf after CRT. Median follow-up time was 36.0 months (interquartile range 18.2-75.7). During the follow-up period, 90 patients died. In the multivariate Cox regression survival analysis, the presence of QRSf before the implantation with or without paced QRSf after CRT were independently associated with all-cause mortality (HR 4.43; 95% CI 1.53-12.80 and HR 3.69; 95% CI 1.16-11.80 respectively). Those without QRSf prior implantation who developed QRSf after CRT did not present significantly higher risk of all-cause mortality. Univariate and multivariate Cox regression analyses for all-cause mortality are presented in Table 1. Figure 1 presents Kaplan-Meier curves for all-cause mortality according to QRSf status before and after CRT implantation. Conclusions According to our results, preimplantation QRSf is an independent predictor of all-cause mortality regardless the resolution or maintenance of QRSf after CRT in patients with HFrEF undergoing CRT. Therefore, patients with QRSf before CRT implantation regardless the paced QRSf status, should be followed more strictly because they are at higher mortality risk.Table 1.Cox Regression Analyses

Left atrial function predicts long-term outcome in hypertension and diabetes across genders

Abstract Introduction In the last decade, peak atrial longitudinal strain (PALS) was ascertained to be superior to conventional echocardiographic indices for secondary cardiovascular (CV) prevention. Purpose Standard and advanced echocardiography including PALS was evaluated to find predictors of prognosis in patients with arterial hypertension and/or diabetes for the optimization of primary CV prevention. Methods Hypertensive and/or diabetic patients >40 years old and in sinus rhythm who underwent a complete cardiological evaluation at our centre in 2008-2015 were retrospectively included. Personal history, physical examination, standard and advanced (speckle tracking) echocardiographic data were collected. The exclusion criteria were previous cv events or cardiac surgery, active pacemaker, more than moderate valvular regurgitation and/or stenosis, missing informed consent. All patients were followed up for a mean time of 11.2±1.3 years for the development of first atrial fibrillation (AF) episode, congestive heart failure hospitalization, transient ischemic attack, stroke, myocardial infarction/coronary revascularization, and CV death. Univariate and multivariable stepwise Cox regressions were performed to estimate Hazard Ratio (HR). Kaplan Meier curves (KM) compared the survival between patients with different ranges of Global PALS. Log-rank test was performed to compare the KM curves. Results This retrospective study included 292 adults (mean age 63.0±9.0 years, 50% female), among which 210 hypertensives and 67 diabetics. Mean left ventricular (LV) ejection fraction (EF) was 58.2±4.9%, mean GLS was -17.0±6.6%, mean left atrial volume was 52.9±24.9ml and mean PALS 29.7±11.1%. During follow up, 110 patients developed at least one cv event: 52 all-cause deaths, 28 CV deaths, 30 heart failure admissions, 31 first AF episode, 18 TIA/strokes, 25 myocardial infarction/revascularization. Dividing the population according to events occurrence, patients with events had similar EF (p= 0.06), while being older (65.8±9.6 vs 61.3±9.0 years) and with a worse diastolic function (E/E’ ratio 10.6±5.0 vs 8.7±3.6), LV longitudinal strain (GLS, -17.7±2.9 vs -15.7±3.4%) and PALS (34.6±9.9 vs 21.6±7.7%, all p <0.001). From univariate statistical analysis, age, E/E’, PAPs, GLS and PALS were all predictors of events, but only age (HR 1.03, p=0.03) and PALS (PALS<22.5% HR 18.99 and PALS 22.5-30 HR 7.68, both p<0.001) remained independently associated with outcome at multivariate analysis. Patients with PALS<22.5 have an event-free survival of 82.4% at 1 year, 49.8% at 5 years and 25.3% at 10 years compared to 100% at 1 year, 98.5% at 5 years and 92.5% at 10 years if PALS PALS>30% (Fig.1). The same results were confirmed in female population (Fig.2). Conclusions If confirmed by larger studies, PALS could be a quick, feasible and reliable part of cardiologic evaluation for prognostic stratification in primary CV prevention in hypertensive and/or diabetic patients.Fig. 1Fig. 2

Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)

Abstract Introduction Free fatty acids (FFAs) serve as vital energy sources in multiple body tissues and they have been associated with elevated cardiovascular disease risk and mortality. There is a scarcity of prospective studies examining the associations between specific FFAs and long-term health outcomes. Purpose To examine the correlation between different FFAs types and all-cause or cardiovascular mortality in a large, nationally representative sample of adults in the United States (US), and examine how different concentrations and types of FFAs may mediate this association. Methods This cohort study included 3719 and 3900 participants in the unsaturated fatty acids (USFAs) and saturated fatty acids (SFAs) populations, respectively, who participated in the US National Health and Nutrition Examination Survey (NHANES) from 2011-2014. Multiple model calibration was performed using univariate and multivariate cox regression analysis to explore the associations between circulating FFAs and all-cause or cardiovascular mortality. Results The UFAs (myristoleic acid (14:1 n-5), palmitoleic acid (16:1 n-7), cis-vaccenic acid (18:1 n-7), nervonic acid (24:1 n-9), eicosatrienoic acid (20:3 n-9), docosatetraenoic acid (22:4 n-6), and docosapentaenoic acid (22:5 n-6)) were associated with an elevated risk of all-cause mortality ((hazard ratio (HR) 1.02 [1.006-1.034]; P=0.004), (HR 1.001 [1.001–1.002]; P＜ 0.001), (HR 1.006 [1.003–1.009]; P＜ 0.001), (HR 1.007 [1.002–1.012]; P = 0.003), (HR 1.027 [1.009–1.046]; P= 0.003), (HR 1.024 [1.012–1.036]; P＜ 0.001) and (HR 1.019 [1.006–1.032]; P = 0.005), respectively), whereas docosahexaenoic acid (22:6 n-3) was linked to a lower risk (HR 0.998 [0.996–0.999]; P = 0.007). Among SFAs, palmitic acid 16:0 was associated with a higher all-cause risk (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) and lignoceric acid (24:0) were associated with lower risks (HR 0.975 [0.959–0.991]; P = 0.002) and (HR 0.992 [0.984–0.999]; P = 0.036). Kaplan–Meier survival curves according to FFAs quartiles shown the highest risk for all-cause mortality was observed in the group with the highest concentration, except serum 23:0. The association between FFAs concentration and cardiovascular mortality in the multivariate analysis indicated that only 22:6 n-3 (HR 0.997 [0.994-1.000]; P=0.035) had a lower risk of cardiovascular mortality in the USFAs group, while none of the SFAs was found to be associated with cardiovascular mortality. While, the relationship between 22:6 n-3, and cardiovascular mortality was characterized by neither a linear nor nonlinear association (P-linear = 0.215; P-nonlinear = 0.260). Conclusion In this cohort of US adults, the types and concentrations of FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs effectively lowered this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.FFA and all-cause mortality

QRS complex fragmentation status before and after cardiac resynchronization therapy predicts hospitalizations for heart failure

Abstract Introduction Cardiac resynchronization therapy (CRT) reduces mortality and hospitalization for heart failure (HF) in selected patients with HF with reduced ejection fraction (HFrEF). However, there is a significant percentage of non-responders who are readmitted for HF after implantation. Several biomarkers and electrocardiographic findings have been suggested as prognostic markers in this group of patients. Fragmentation of the QRS complex (QRSf) has been associated with worse prognosis in several cardiac diseases, but evidence in patients undergoing CRT remains to be limited. Purpose To evaluate if the changes in QRSf status before and after CRT implantation have a prognostic role in patients undergoing CRT in terms of hospitalization for HF. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. QRSf complex was defined by the presence of different RSR′ patterns including an additional R-waves (R′) and notches of the R-wave and S-wave in two contiguous leads corresponding to a main coronary artery territory in a 12-lead surface electrocardiogram performed before and after CRT. Results A total of 244 patients (mean age 72 ± 10 years, 80% male) were included. The etiology of the LV systolic dysfunction was ischemic in 50.0%. Mean LVEF before implantation was 25 ± 9% and mean paced QRS width was 141 ± 23 ms. CRT-D was implanted in 176 patients (72.2%). At baseline, 150 patients had a QRSf. After CRT implantation, 69 (28.4%) patients experimented a change in QRSf status: 29 patients (11.9%) without prior QRSf developed QRSf, whereas 40 patients (16.5%) resolved QRSf after CRT. Median follow-up time was 36.0 months (interquartile range 18.2-75.7). At follow-up, 90 patients died and 91 presented at least one hospitalization for HF. Multivariate Cox regression survival analysis showed that development of QRSf after CRT implantation (HR 8.87; 95% CI 1.85-42.50) and the presence of QRSf before implantation with or without paced QRSf after CRT (HR 8.21; 95% CI 1.75-38.50 and HR 16.70; 95% CI 3.88-71.80 respectively) were independently associated with hospitalizations for HF. Univariate and multivariate Cox regression analyses for HF hospitalization are presented in Table 1. Figure 1 presents Kaplan-Meier curves for QRSf status and hospitalizations for HF. Conclusions According to our results, QRSf status before and after CRT have a significant prognostic role in terms of hospitalization for HF after CRT, especially in those who develop QRSf after CRT and those with baseline QRSf regardless QRSf status after CRT. The worse prognosis was observed in those with QRSf before and after CRT. Therefore, these patients should be followed more strictly because they are at higher risk of decompensation.Table 1.Cox Regression Analyses

Effect of left atrial function on cardiovascular outcome in non-dilated left ventricular cardiomyopathy

Abstract Background This study aimed to determine whether atrial function and strains can provide the greatest or joint incremental prognostic value in patients with non-dilated left ventricular cardiomyopathy (NDLVC) over a long follow-up period. Methods One hundred sixty-four NDLVC patients were included retrospectively. Comprehensive clinical evaluation and echocardiographic investigations were obtained, including measurements of strain derived left atrial (LA) reservoir, conduit, booster strain. All patients were followed up for adverse cardiac events (MACE) including all-cause mortality, hospitalization due to heart failure aggravation. The predictors of MACE were examined with univariable and multivariable Cox regression analysis. Subsequently, nested Cox regression models were built to evaluate the incremental prognostic value of strain parameters. Patient survival was illustrated by Kaplan–Meier curves and differences were evaluated by log-rank test. Results During a median follow-up of 3.8 years, MACEs were identified in 34 (21%) patients. Cox regression models showed that the predictive value of LA conduit strain was independent from and incremental to LAVi and baseline variables. Age, E/e', RASP and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.05). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, age, RASP remained associated in the multivariable model (LA conduit strain HR: 2.14 [95% CI: 1.37-3.87; P < 0.007]; age HR: 1.05 [95% CI: 1.01-1.10; P = 0.020]; and RASP HR: 1.07 [95% CI: 1.01-1.14; P = 0.021]), whereas LVEF, LAVi were not. Adding LA conduit strain to other independent predictors (age and LAVi) improved the prediction of MACEs. (p < 0.05). Also, when a Kaplan Meier graph was obtained for the occurrence of MACE based on LA conduit strain 17%, a significant difference was shown between the two groups. Conclusion LA conduit strain provided the good prognostic value and added incremental value to conventional clinical predictors for patients with NDLVC.Incremental value of LA strainKM according to LA strain 17%

Mortality risk in patients with carotid artery disease undergoing carotid endarterectomy compared to the general population

Abstract Background Patients with carotid artery disease undergoing carotid endarterectomy (CEA) appear to be at high risk of all-cause mortality during their follow-up. However, the possible predictors of this adverse outcome are not elucidated yet. Purpose We aimed to test cardiovascular (CV) risk factors as possible predictors of all-cause mortality in patients undergoing CEA and to determine whether there is a difference between the mortality rate of our study cohort and the general population. We hypothesize that CEA-treated patients have a higher mortality rate during follow-up after surgery than the general population, which is not related to the presence of CV risk factors. Methods We prospectively enrolled and followed up patients undergoing CEA. Univariate and multivariable Cox regression were performed to test whether common CV risk factors (demographics, laboratory values, comorbidities, and events before CEA) were predictive of all-cause mortality. We then compared the standardized mortality ratio (SMR) of our population and the age-sex-matched Minnesota (MN) general population at 5,10, and 21 years of follow-up after CEA. Results A total of 710 patients were followed for a median of 7.1 [2.9-11.9] years after CEA. Mortality occurred in 198 (27.0%) patients during the follow-up. The median time to event was 11.0 [10.0-12.0] years. Age was the only predictor of all-cause mortality in CEA-treated patients in multivariable models adjusted for known CV risk factors (Model 1: HR 1.03 [95%CI 1.01-1.06]; p=0.004; Model 2: HR 1.02 [95%CI 1.00-1.04]; p=0.023) (Table 1). However, the CEA-treated group had a higher mortality rate than would have been expected in the MN population (log-rank p<0.001) (Fig.1A). Compared to the MN population, at 5 years of follow-up only patients <60 years old had a higher SMR (4.53 [1.95-8.92]; p=0.001), whereas, at 10 years and 21 years of follow-up, our study population had a higher mortality rate at any age (Fig.1B). Conclusions The elevated mortality risk post-CEA in our cohort cannot be solely attributed to chronological aging. The underlying process of atherosclerosis likely contributes to all-cause mortality, and plaque characteristics may offer additional insight into the risk stratification of this patient group.All cause mortality predictors after CEAStudy population vs. MN population SMR

Role of inflammation and cholesterol efflux in myocardial infarction patients without standard modifiable risk factors

Abstract Background A substantial proportion of ST-segment elevation myocardial infarction (STEMI) patients has no standard modifiable cardiovascular risk factors (SMuRF) at admission. Knowledge on pathogenesis and risk markers of mortality in these patients remain limited. Aims We described the characteristics and prognosis of SMuRF-less patients admitted for a first STEMI in the light of recent prognostic biomarkers. Methods Baseline characteristics including interleukin (IL)-1β, hs-CRP and serum cholesterol efflux capacity were compared between patients with and without SMuRF. Determinants of 1-year all-cause mortality were assessed using univariable and multivariable Cox regression analyses. Results Among the 1604 patients included, 178 (11.1%) were SMuRF-less. SMuRF-less patients were older (66.9 ± 15.3 vs 61.9 ± 13.9, p<0.001), less often men (66.9 vs 75.9%, p<0.001) and had lower body mass index (24.2 ± 3.9 vs 26.0 ± 4.4, p<0.001) compared to patients with ≥1 SMuRFs. SMuRF-less patients presented higher rates of altered LVEF<45% and killip≥2 at admission (31.8% vs 22.8%, p=0.014 and 19 vs 12.9%, respectively, p=0.027) without differences in proportions of late STEMI presenters (symptoms-to-balloon time >360 min) did not differ between groups. SMuRF-less patients had lower rates of revascularization (82 vs 92.3%, p<0.001) and received less guidelines recommended medications (statins, β-blockers or angiotensin-converting enzyme (ACE) inhibitors) at discharge; p<0.001 for all. Compared to patients with SMuRF, SMuRF-less patients had lower serum cholesterol efflux capacity (0.79 ± 0.16 vs 0.83 ± 0.16, respectively, p<0.001), were more often in the highest tertile of IL-1β (28.7% vs 18.9%, respectively, p=0.002) with a trend towards more patients within the highest hs-CRP level tertile (24.7% vs 19.1%, respectively, p=0.077). Crude rates of mortality were more than doubled in the SMuRF-less group (18.5% vs 7.7%, respectively, p<0.001). After multivariable adjustment SMuRF-less status was associated with a higher rate of mortality at one year aHR 1.87 [1.05-2.38], p=0.029) as well as inflammation biomarkers IL-1β (HR 1.81 [1.23-2.66], p=0.003) and high tertiles of hs-CRP (HR 1.87 [1.31-2.66], p<0.001) whereas having a high serum cholesterol efflux capacity was associated with a lower mortality (HR 0.27 [0.09-0.87], p=0.0208). Conclusion In STEMI patients, SMuRF-less patients have higher levels of inflammatory biomarkers and more frequent defective serum cholesterol efflux capacity, are undertreated, and have higher rate of mortality than patients with standard modifiable cardiovascular risk factors. Optimized management of such patients is needed.

Association between surgery treatment delays and survival outcomes in patients with esophageal cancer in Hebei, China

IntroductionThe delays in cancer therapies have the potential to impact disease progression by allowing the unchecked growth and spread of cancer cells. However, the understanding of the association between treatment waiting time and survival outcomes in patients with esophageal cancer (EC) is limited. This study aims to assess the impact of waiting time on survival outcomes among EC patients in Hebei province, which is recognized as one of the high-risk areas for EC in China.MethodsA total of 9,977 non-metastatic EC patients who underwent surgical treatment were identified between 2000 and 2020. The survival outcomes of overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier methodology. Univariate and multivariate Cox regression analysis was employed to evaluate the impact of treatment delays on OS and CSS.ResultsThe average delay time for initiating EC surgical treatment after diagnosis was 1.31 months (95%CI=1.29–1.34). Patients with a long delay (≥ 3 months) in treatment, comprising 9977 EC patients, exhibited significantly lower rates of 3-, 5-, and 10-year OS and CSS compared to those without any delay in treatment initiation. A long delay in EC treatment independently associated with an elevated risk of all-cause and cancer-cause mortality among various patient subgroups, including males, older individuals, single individuals, low-income patients, residents of nonmetropolitan counties, as well as those diagnosed with poorly differentiated and stage IV EC.DiscussionThe long delay of treatment initiation impacts the outcomes of OS and CSS in EC patients. Optimizing treatment timing may enhance life expectancy for individuals diagnosed with EC.

Increased serum level of IL-6 predicts poor prognosis in anti-MDA5-positive dermatomyositis with rapidly progressive interstitial lung disease

BackgroudAnti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis (anti-MDA5-positvie DM) is a subtype of dermatomyositis with a poor prognosis, characterized by rapidly progressive interstitial lung disease (RP-ILD). The study aims to investigate the significance of serum cytokines profiles and peripheral lymphocytes in predicting prognoses of anti-MDA5-positvie DM with RP-ILD. Furthermore, it seeks to analyze longitudinal data of lymphocytes during hospitalization to identify distinct trajectories and cluster patients accordingly.MethodsA total of 168 patients with anti-MDA5-positive DM were enrolled in this retrospective study from two cohorts. Univariate and multivariate Cox regression analyses were conducted to determine the predictors of 6-month all-cause mortality and RP-ILD. Group-based trajectory modeling (GBTM) was employed to model the trajectories of longitudinal peripheral lymphocytes.ResultsIn the multivariate Cox regression analysis, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, lymphocytes from 0.5 to 1.0 × 109 /L, older age, and elevated LDH were identified as independent predictors of 6-month all-cause mortality. Furthermore, IL-6 ≥ 13.41pg/mL, lymphocytes < 0.5 × 109 /L, and lymphocytes from 0.5 to 1.0 × 109 /L were found to be independent predictors of RP-ILD. Additionally, three trajectory groups of lymphocytes within the first week after admission were established based on GBTM. These groups included: Group 1, with low-level of lymphocytes that declined; Group 2, with medium-level of lymphocytes that slightly rose; and Group 3, with high-level of lymphocytes that rose. Notably, group 1 showed the highest mortality (90.7%) and all experiencing RP-ILD. Increased expression of IL-6 in lung tissues was observed in two cases with RP-ILD compared to two cases without RP-ILD. We also found the increased infiltration of CD4 + and CD8 + T cells, particularly CD8 + T cells, in lung tissues from patients with RP-ILD.ConclusionsOur study demonstrated that increased level of serum IL-6 (≥ 13.41pg/mL) and severe lymphopenia were promising predictors of 6-month all-cause mortality and the occurrence of RP-ILD in anti-MDA5-positive DM patients. Furthermore, tracking distinct trajectories of lymphocytes during hospitalization can be utilized to cluster patients.

SAR1A Induces Cell Growth and Epithelial–Mesenchymal Transition Through the PI3K/AKT/mTOR Pathway in Head and Neck Squamous Cell Carcinoma: An In Vitro and In Vivo Study

Objectives: Head and neck squamous cell carcinoma (HNSCC) ranks sixth globally, with a 50% five-year survival rate. SAR1A exhibits high expression levels in various tumor types, yet its specific role in HNSCC remains to be clarified. Methods: In vitro assays, such as CCK8, EdU, colony formation, wound-healing, transwell, and Western blotting analyses, as well as in vivo assays, such as tumor xenografts and lung metastasis models, were conducted to evaluate the impacts of SAR1A on HNSCC proliferation, migration, and invasion. Transcriptome sequencing and KEGG enrichment pathway analysis revealed evident alterations in the PI3K/AKT/mTOR(PAM) pathways. LY294002 (a PI3K/AKT inhibitor) was used to investigate the role of the PAM pathway in proliferation, migration, and invasion in HNSCC. Results: Univariate and multivariate Cox regression were conducted to screen SAR1A as a gene prognostic biomarker in HNSCC, and it was validated in the Cancer Genome Atlas (TCGA) database. Functional assays demonstrated that the depletion of SAR1A leads to suppressed proliferation, migration, and invasion of HNSCC cells. This is accompanied by a decrease in the expression of epithelial–mesenchymal transition (EMT)-related markers in HNSCC cell lines. In addition, the diminished capacities of proliferation, migration, and invasion observed in SAR1A knockdown cells were reversed upon the overexpression of SAR1A. Furthermore, RNA-seq and KEGG enrichment analysis demonstrated a significant alteration in the PAM pathway following SAR1A knockdown. LY294002 effectively mitigated the increased proliferation, migration, and invasion induced by SAR1A overexpression. Conclusions: SAR1A facilitates HNSCC proliferation and EMT via the PI3K/AKT/mTOR pathway.

Remnant cholesterol and mortality in 37.559 patients from LIPIDOGRAM 2004, 2006 and 2015 studies

Abstract Introduction Remnant cholesterol (remnant-C) is produced by metabolism of triglyceride rich proteins and contributes to residual cardiovascular (CVD) risk. Purpose To asses association between remnant cholesterol and all-cause mortality in a large cohort of patients under the care primary care physicians. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. Patients (n=47,398) recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatment, and lifestyle. In the present analysis we included consecutive patients with body mass index (BMI) &amp;gt;18.5 kg/m2 aged 18-70 years. Median follow up was (5.3 years (interquartile range 5.7-17.3). For this analysis we approved the cut-off point of fasting remnant cholesterol &amp;gt;30 mg/dL (&amp;gt;0.77 mmol/L) that differentiated subjects at high risk of cardiovascular events. We used univariate and multivariate Cox regression modelling to assess the association between remnant-C and all-cause mortality. Results Finally, 37,559 patients were included meeting the inclusion criteria and for which the follow-up data was available. Mean remnant-C concentration was: 27 mg/dl / 0.7 mmol/l (standard deviation 15 mg/dl/ 0.38 mmol/l). Remnant-C was associated with 5-year mortality and overall mortality during the study period, with hazard ratios (HR) of 1.21 (95% CI: 1.04-1.41, p&amp;lt;0.001) and 1.42 (95% CI: 1.32-1.53, p&amp;lt;0.001) for each 1 mmol/l increase, respectively. After adjusting for age, sex, BMI, education level, place of residence, hypertension, diabetes mellitus, smoking, previous myocardial infarction, metabolic syndrome presence, and statin and fibrate treatments, remnant-C was associated with long-term mortality—HR (per 1 mmol/l) of 1.08 (95% CI: 1.00-1.17, p=0.049)—but not with 5-year mortality—HR (per 1 mmol/l) of 0.97 (95% CI: 0.83-1.13, p=0.7). Predefined level of remnant-C &amp;gt; 30 mg/dl (0.77 mmol/l) was associated with higher 5 year (HR- 1.15, 95%CI (1.02-1.31, p=0.021) (Figure 1A) and long-term all-cause mortality (HR- 1.26, 95%CI (1.19-1.33, p&amp;lt;0.001) (Figure 1B). Conclusions Higher remnant-C cholesterol levels are associated with long term all-cause mortality in patients aged 18-70 years.

Combined 3D left ventricular-arterial coupling and 3D left atrial-ventricular coupling indices could better predict MACE in young patients with STEMI

Abstract Background Left ventricular arterial coupling index (VAC) proved to be a key determinant of cardiovascular performance. Previous trials also emphasized the prognostic value of left atrial-ventricular coupling index (LACI) that was independently associated with cardiovascular death and all-cause mortality. Both indices have been associated with disease severity and adverse outcomes. Purpose We aimed to evaluate the prognostic role of 3D VAC, 3D LACI and their combination assessed by 3D echocardiography in a cohort of young patients with STEMI. Patients and methods In this prospective study we enrolled 76 young consecutive patients (under 50 years old) with STEMI treated by primary PCI who underwent both 2D and 3D echocardiography. 3D VAC was calculated as the ratio between arterial elastance (EA) and end-systolic left ventricular elastance (EES), based on a formula proposed by Chen. 3D LACI was determined as the ratio between 3D left atrial end-diastolic volume (minimal atrial volume) and 3D left ventricular end-diastolic volume. Patients were followed up for one year after STEMI and the primary endpoint was the occurrence of MACE defined as death from cardiovascular causes, heart failure requiring hospital admission, or repeat revascularisation. Results Out of 76 patients, 15.8% had an adverse event during the 12 months follow up period. We divided the patients in two groups according to the presence or absence of MACE. Patients with MACE had higher VAC (2.15±0.62 vs. 1.25±0.29%, p&amp;lt;0.0001) and higher LACI (25.1±7.17% vs. 18.3±6.58%, p=0.002). In ROC analysis VAC and LACI combined had the best AUC for MACE prediction (AUC 0.961, p&amp;lt;0.0001), followed by VAC (AUC 0.922, P&amp;lt;0.0001), and then, LACI (AUC 0.772, P&amp;lt;0.001). For each variable we determined a cut off value. A value over 1.7 for VAC and 23.83% for LACI can predict unfavourable outcome with 83.3% sensitivity and 97.1% specificity for VAC and 67% sensitivity and 80% specificity for LACI. In both univariate and multivariate COX regression analysis, both VAC and LACI remained independent predictors for MACE. Moreover, their combination proved to have better predictive value for adverse events compared to each taken separately. We divided the study population into 4 groups: Group 1: VAC &amp;lt; 1.7 and LACI &amp;lt; 23.83%. Group 2: VAC &amp;lt;1.7 and LACI &amp;gt; 23.83%. Group 3: VAC &amp;gt; 1.7 and LACI &amp;lt; 23.83% and Group 4: VAC &amp;gt; 1.7 and LACI &amp;gt;0.23.83%. Kaplan Meier analysis shows significant differences among groups (log rank χ2 = 35.48, p &amp;lt; 0.0001). Calculation of Kaplan-Meier curves for the four groups indicated that the combination of the VAC &amp;gt; 1.7 and LACI &amp;gt; 23.83% had the strongest predictive power for MACE. Conclusion In conclusion 3D VAC and 3D LACI combined are better at predicting adverse events than each variable taken separately and could be used for a more accurate risk stratification in young patients with STEMI.

Development of a Novel Risk Signature for Predicting the Prognosis and Immunotherapeutic Response of Prostate Cancer by Integrating Ferroptosis and Immune-Related Genes.

Ferroptosis and immune response correlation studies have not been reported in prostate cancer (PCa), and the main goal of this paper is to identify biomarkers that can be used for early diagnosis of prostate cancer. Data on PCa were retrieved from the TCGA and MSKCC2010 databases. Thereafter, the differentially expressed ferroptosis-related genes (DE-FRGs: ACSF2) and immune-related genes (DE-IRGs: ANGPT1, NPPC, and PTGDS) were identified using the "limma" package. Additionally, we used univariate and multivariate Cox regression analyses to obtain biochemical relapse (BCR)-free survival-related genes and construct a risk signature. Patients with high-risk scores were characterized by poor BCR-free survival, relatively low immune cell abundance, and comparably weak expression of immune checkpoint molecules. Moreover, gene set variation analysis (GSVA) was performed to explore the biological pathways related to the risk signature. Single sample gene set enrichment analysis (ssGESA) was applied to evaluate the status of immune cells in patients with PCa, which demonstrated that the risk score was intimately affiliated with immune response and cancer pathways. Ultimately, the connection between the risk score and response of PCa patients to immunotherapy was appraised using the TIDE algorithm. The TIDE algorithm implied that the high-risk score PCa population might benefit more from immunotherapy regimens. Finally, qRT-PCR were used to evaluate the expression of DE-FRGs and DE-IRGs in PCa cell and normal prostate epithelial cells. The result of qRT-PCR showed that the mRNA expression levels of ACSF2, ANGPT1, NPPC, and PTGDS in normal prostate epithelial cell were higher than that in PCa cells. Therefore, a risk score model was generated based on one DE-FRG and three DE-IRGs, which could predict the BCR-free survival and response of immunotherapy for patients with PCa.

Comparative analysis of a novel preoperative stratification method versus traditional scores in patients with severe aortic stenosis undergoing aortic valve surgery

Abstract Introduction It is crucial to consider factors that complicate the indication of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS), such as narrow valve ring, extensive calcification or inadequate vascular access. (1-4) Thus, aortic valve replacement surgery (SAVR) remains a recommended indication, with its pre-surgical stratification being a challenge. (1-3) Despite the widespread use of scores like the STS and EuroSCORE II, they exhibit limitations, being validated primarily for populations outside Latin America and focusing predominantly on individual factors while often neglecting structural parameters like left ventricular hypertrophy, diastolic dysfunction, or left atrium volume. (3-5) Purpose This study aimed to assess whether a novel modified Généreux stratification method offers superior predictive value for postoperative mortality in AS patients compared to traditional scoring systems. Methods We conducted a retrospective, single-center study involving patients with confirmed severe AS who underwent aortic valve replacement surgery between January 2017 and December 2021. The new stratification method categorized patients into three stages based on echocardiographic parameters (see Figure 1). Univariate and multivariate Cox regression analyses were conducted to identify predictors of mortality, with survival analysis performed using Kaplan-Meier curves. A p-value &amp;lt;0.05 was considered statistically significant. Results A total of 508 patients were included in the study. Stage 1 patients had a lower median age (62 years vs. 67 years in stages 2 and 3). The median EuroSCORE and STS were 2.75 and 2.62%, respectively, with stage 3 showing significantly higher scores (p ≤0.001). Over a median follow-up of 81 months, 56 deaths occurred (11%). Kaplan-Meier curve analysis revealed significant differences in all-cause mortality among the three groups (HR 4.073, log-rank p≤0.001), as illustrated in Figure 1. Multivariate analysis identified the three preoperative stages (HR 3.22, [95% CI 1.44-7.20], p=0.004) and mean transaortic gradient (HR 0.96, [95% CI 0.92-0.99], p=0.021) as independent predictors of mortality. The new stages demonstrated a superior area under the ROC curve of 0.758 compared to traditional scores (see Figure 1). Conclusions The novel three-stage preoperative classification and low transaortic gradient serve as significant predictors of mortality in patients undergoing SAVR. These stages exhibit robust predictive capability for mortality compared to EuroSCORE II and STS.Baseline and multivariate analysisKaplan-meier and ROC curve

The very long-term risk of stroke after acute coronary syndrome and geographic differences. The ABC-10* study on heart disease

Abstract Background Little is known about the very long-term risk of stroke among acute coronary syndrome (ACS) survivors. Methods In this prospective study, we enrolled 535 ACS patients admitted to hospitals in three Italian provinces, discharged alive and followed for 24 years or death. The patient's residency was classified into three urban and three nearby rural areas. Results All patients completed the follow-up (6142 Perso-years). 85 (16%) patients suffered an acute stroke. Patients median age was 67 years, 70% were male, and 318 patients were residing in rural areas. Patients who had a stroke and those who had not shared most of the demographic and clinical characteristics. The incidence rate of overall stroke was 14/1000 person-year. Cox analyses showed older age (HR 3.13;95%CI 2.31-4.26), male gender (HR 1.88;95%CI 1.20-2.95), baseline diabetes (HR 2.25 95%CI 1.37-3.69), heart failure (HR 2.69;95%CI 1.71-4.24), and higher albumin/creatinine ratio (HR 1.75;95%CI 1.33-2.30) were all associated with an increased risk of stroke. while higher baseline eGFR, reperfusion, statin and beta-blockers treatment during follow-up were associated with a decreased risk; HR (0.55 (95%CI 0.42-0.72), 0.45(95%CI 0.29-0.71), 0.21(95%CI 0.13-0.34), and 0.37(95%CI 0.23-0.57), respectively). In the multivariate analysis, only older age (HR1.55;95%CI 1.08-2.21; p=0.02) was an independent predictor of stroke while statin treatment was independently associated with a lower risk (HR 0.35;95% CI 0.21-0.58; p&amp;lt;0.0001). However, all these variables did not predict the risk of stroke in competing risk regression analysis where death was treated as the competing event. A sub-analysis of the 43 patients who had a fatal stroke (FS) revealed 7/1000 person-year FS IR. The Cox regression and competing risk analyses of predictors of FS showed similar results. Interestingly, we observed an association between geographic areas of residence and the long-term FS risk as the risk increased going from rural to urban (HR 2.08;95%CI 1.14-3.80; p=0.02) areas and from north to middle and south provinces (HR 1.47;95%CI 1.00-2.15; p=0.04) in the univariate Cox regression analysis. Results kept true using multivariate Cox and Competing risk regression models. Conclusion This analysis reveals the significant urban-rural difference in the very long–term risk of fatal stroke among unselected ACS patients which highlights the importance of implementing a preventive policy based on area-specific knowledge.

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&amp;lt;0.001). Conclusion Our study developed and validated a practical nomogram for predicting the 2-year risk of MACCE in elderly patients with ACS.

Left ventricular pressure-strain loops for the assessment of myocardial work in a low-risk community-based cohort: associations with long-term prognosis

Abstract Background Non-invasive left ventricular (LV) pressure-strain loop analysis is a novel technique for the evaluation of global myocardial work (GMW) that provides additional insights on LV contractility and energetics beyond traditional metrics, such as ejection fraction (EF) and global longitudinal strain (GLS). Despite its established value in numerous cardiac diseases, there remains limited data on its predictive power in a low-risk population. Purpose Our objective was to determine the long-term prognostic value of GMW in a population-based screening sample comprising low-risk adult individuals. Methods We retrospectively identified 1562 volunteers from a population-based screening program (mean age 54±15 years, 59% female), with a median follow-up time of 11 years. All subjects underwent 2D echocardiography to measure LV EF, GLS, peak atrial longitudinal strain (PALS), GMW index (GMWI), global wasted work (GWW), and GMW efficiency (GMWE). The primary endpoint was all-cause mortality. Results 191 subjects (12,2%) met the primary endpoint. Subjects who experienced adverse outcomes exhibited significantly lower LV EF (dead vs. alive; 49.7±8.3 vs. 52.7 ±6.4 %, p&amp;lt;0.001), GLS (-18.7±4.1 vs. -20.4±3.6 %, p&amp;lt;0.001), PALS (33.6±15.7 vs. 44.2±15.2 %, p&amp;lt;0.001), and GMWI (2181.7±591.3 vs. 2286.8±482.5 mmHg%, p=0.008). Furthermore, subjects with adverse outcomes had significantly higher GWW (132.6±249.4 vs 95.1±113.4 mmHg%, p&amp;lt;0.001) and, consequently, lower GMWE (0.95±0.05 vs. 0.96±0.03, p&amp;lt;0.001). Univariate Cox regression analysis revealed GMWI to be a significant predictor of mortality (hazard ratio for 100 units 0.957 [95% CI: 0.929-0.986], p=0.004), alongside GMWE (hazard ratio for 1 percent 0.940 [95% CI: 0.912-0.968], p&amp;lt;0.001), and GWW (hazard ratio for 100 units 1.124 [95% CI: 1.063-1.188], p&amp;lt;0.001). By multivariable Cox regression encompassing age, sex, GMWI, LVEF, GLS, PALS, and systolic blood pressure, GMWI remained an independent predictor of all-cause mortality (hazard ratio 0.932 [95% CI: 0.874-0.995], p=0.035), while GLS was not an independent predictor. Moreover, integrating the Atherosclerosis Risk in Communities (ARIC)-HF risk factors (age, sex, race, coronary artery disease, antihypertensive medication, blood pressure, diabetes mellitus, body mass index, heart rate, and smoking status), we constructed a multivariate model with GMWI. GMWI was still an independent predictor of mortality (hazard ratio for 100 units 0.941 [95% CI: 0.903-0.980], p=0.004). Using the GMWI cut-off value of 1576 mm Hg% (based on a large-scale healthy population study), the population was divided into 2 groups. Using Kaplan-Meier curves (Figure), the outcomes of the groups differed significantly (log-rank p&amp;lt;0.001). Conclusions GMW provides added value in clinical outcome prediction, even in low-risk individuals. Myocardial work analysis is a promising approach for a comprehensive evaluation of cardiac function and for cardiovascular risk stratification.