Independent Predictor Of All-cause Mortality Research Articles

Association between D-dimer-to-albumin ratio and 28-days all-cause mortality in patients with sepsis.

We aimed to investigate the correlation between the serum D-dimer (D-D) to albumin (ALB) ratio (DAR) and 28-day all-cause mortality in patients with sepsis. Data from sepsis patients admitted to the intensive care unit (ICU) of Wuhan Fourth Hospital from October 2021 to January 2024 were collected. Univariate cox analysis was performed for mortality factors in sepsis patients, and multiple cox regression models were used to analyze independent mortality risk factors. The receiver operating characteristics (ROC) curve was used to analyze the value of DAR in predicting sepsis mortality, and the Kaplan-Meier method was used to plot the survival curve. A total of 833 patients with sepsis in the ICU of our hospital were selected and divided into alive group (n = 574) and death group (n = 171) according to their 28-day survival. In the death group, D-D and DAR levels were higher, while ALB levels was lower than in the alive group. Spearman analysis found that DAR level were positively correlated with APACHE II and SOFA scores. Multivariate cox regression analysis showed that DAR was an independent predictor of all-cause mortality within 28 days of admission for sepsis patients (HR = 17.956, 95% CI 3.435-93.851, p < 0.001). The ROC curve results showed that the cut-off value of DAR was 0.068, with a sensitivity of 78.4% and a Youden index of 0.375, predicting mortality in sepsis patients, with an area under curve (AUC) of 0.767 (95% CI 0.744-0.790, P < 0.001). Further analysis divided patients into low DAR (DAR < 0.068) and high DAR (DA ≥ 0.068) groups based on the optimal cut-off value. Kaplan-Meier analysis found higher mortality in the high DAR group. DAR is an independent predictor of all-cause mortality within 28 days of admission in sepsis patients. Combining these two indicators can improve clinical treatment guidance and reduce the risk of death.

Ratio of red blood cell distribution width to albumin level and risk of mortality in sarcopenic obesity.

The aim of this study was to investigate the relationship between red blood cell distribution width and albumin ratio (RAR) levels and mortality in adult patients with sarcopenic obesity in the United States. The study included 1,361 adult patients with sarcopenic obesity from the National Health and Nutrition Examination Survey (1999-2006). The X-tile was used to determine the optimal subgroup thresholds for RAR values, and propensity score matching (PSM) was employed to reduce baseline bias. Cox regression analysis, Kaplan-Meier survival curves, and restricted cubic spline analysis were utilized to assess the relationship between RAR levels and all-cause and cardiovascular mortality. Subgroup analysis and the Subpopulation Treatment Effect Pattern Plot were employed to determine survival advantages across different subgroups. Time-dependent ROC analysis to evaluate the accuracy of RAR level in predicting survival outcomes at different time points. Post-PSM multifactorial Cox regression analyses revealed that RAR was a significant independent predictor of all-cause mortality (HR 1.487, 95% CI: 1.259-1.756) and an independent risk factor for cardiovascular mortality (HR 1.487, 95% CI: 1.260-1.758) in patients with sarcopenic obesity. The survival advantage was consistent across subgroups. Restricted cubic spline analysis indicated an approximate S-shaped association between RAR levels and mortality. Time-dependent ROC curves demonstrate that the areas under the all-cause mortality curves at the RAR level for 1-year, 3-year, 5-year, and 10-year are 0.79, 0.66, 0.64, and 0.63, respectively. The areas under the cardiovascular mortality curve are 0.80, 0.70, 0.66, and 0.61, respectively. Moreover, in comparison to the baseline model lacking covariates, the AUC values of the joint model exhibited heightened levels at various time points. Therefore, We demonstrated that the RAR level is an independent prognostic factor for mortality risk in the American population with sarcopenic obesity, and it is reasonable to consider the RAR level as a simple and effective risk prediction tool.

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

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

Epicardial adipose tissue volumes for long-term risk stratification in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Abstract Background Accurate risk stratification is important to improve patient selection and outcome of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). As epicardial adipose tissue (EAT) is discussed to be involved in cardiovascular disease, it could be useful as a marker of poor prognosis in patients with severe AS undergoing TAVR. Purpose We hypothesized that EAT impacts long-term outcome of patients with severe AS undergoing TAVR independently from subtype and other risk factors. Methods A total of 416 patients diagnosed with severe AS by transthoracic echocardiography were assigned for TAVR and enrolled for systematic assessment. Patients underwent clinical surveys and 5-year long-term follow-up, with all-cause mortality as the primary endpoint. EAT volume was quantified on pre-TAVR planning CTs. Patients were retrospectively dichotomized at the median of 74cm3 of EAT into groups with low-EAT and high-EAT volumes. Mortality rates were compared using Kaplan-Meyer plots and uni- and multivariable cox regression analyses. Results A total number of 341 of 416 patients (median age 80.9years, 45% female) was included in the final analysis. Patients with high-EAT volumes had similar short-term outcome (p=0.794) but significantly worse long-term prognosis (p=0.023) compared to patients with low-EAT volumes. Increased EAT volumes were associated with worse long-term outcome (HR1.59;p=0.031) independently from concomitant cardiovascular risk factors, general type of AS and functional echocardiography parameters of AS severity (HR1.69;p=0.013). Conclusion Increased EAT volume is an independent predictor of all-cause mortality in patients with severe AS undergoing TAVR. It can be easily obtained from pre-TAVR planning CTs and may thus qualify as a novel marker to improve prognostication and management of patient with severe AS.Graphical Abstract

Impact of rhythm control strategy on outcomes in patients with first diagnosed atrial fibrillation in an 11-year real-world registry

Abstract Background Atrial fibrillation (AF) is a highly prevalent arrhythmia with a high burden of disease. This sub-study of the Heidelberg Registry of Atrial Fibrillation (HERA-FIB) sought to evaluate clinical characteristics, treatment strategies and outcomes in patients with first diagnosed AF (FDAF). Methods Patients with AF presenting to the emergency department (ED) of an University Hospital between June 2009 and March 2020 were consecutively enrolled. Follow-up was performed for all-cause mortality, stroke, major bleeding and myocardial infarction (MI). Outcomes were were related to patients with FDAF or pre-existing AF, as well as assigned treatement strategy (rhythm vs. rate control). The trial was registered at ClinicalTrials.gov Identifier: NCT05995561. Results Overall 2,758 (27%) of all patients presented with FDAF. Compared to FDAF, patients with pre-existing AF showed higher all-cause mortality HR 1.41 (95%CI 1.28-1.55, p&amp;lt;0.0001) and major bleeding events 1.29 (95% CI 1.06-1.56, p=0.0098). Non-implementation of rhythm control in FDAF was seen in 2,079 cases (75.4%) and was associated with an excess of all-cause mortality HR 1.66 (95%CI 1.30-1.99, p&amp;lt;0.0001) and incident MI HR 1.79 (95% CI 1.03-3.09, p=0.0385). A non-implementation of rhythm control remained an independent predictor for all-cause mortality and MI even after adjustment for significant univariate variables aHR: 1.34 (95%CI: 1.04-1.72, p=0.0234) and aHR: 1.79 (95%CI: 1.03-3.09, p=0.0385). Conclusion Real-world data from FDAF patients presenting in the setting of an ED showed a potential benefit regarding mortality and MI for rhythm control strategy. Further research is needed to validate this hypothesis.

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

Myocardial work and aortic valve stenosis cardiac damage stages are predictors of all-cause mortality in patients undergoing transcatheter aortic valve replacement

Abstract In aortic stenosis (AS) patients, assessment of left ventricular (LV) systolic function is complicated due to the significant impact of increased afterload on conventional parameters. Myocardial work (MW) analysis, a novel echocardiographic method adjusts myocardial deformation to instantaneous LV pressure which may better reflect the LV contractile state. Importantly, long-term LV pressure overload has marked backward effects beyond the LV: classification of this extravalvular cardiac damage effectively represents the involvement of the cardiopulmonary system in AS. Both MW and cardiac damage staging could hold remarkable prognostic power in the clinically complex population of transcatheter aortic valve replacement (TAVR) candidates. Accordingly, our aim was to assess the prognostic value of MW analysis and cardiac damage staging in patients undergoing TAVR. We enrolled 289 patients (79±6 years, 41% female) prior to TAVR. Echocardiographic measurements were performed one day before the procedure. We calculated LV ejection fraction (EF) and by speckle-tracking echocardiography global longitudinal strain (GLS), as well. Global constructive work (GCW) was quantified with dedicated software and LV pressure was estimated using transaortic mean gradient and systolic blood pressure. Based on the echocardiographic data, we also determined the extent of cardiac damage associated with AS: patients were classified as Stage 0 (no cardiac damage), Stage 1 (LV damage), Stage 2 (mitral valve or left atrial damage), Stage 3 (pulmonary artery vasculature or tricuspid valve damage), or Stage 4 (right ventricular damage). Our primary outcome was all-cause mortality, reached by 68 patients (median follow-up: 26 months). In our cohort, preprocedural EF was 47±13 %, GLS was -12.3±4 %, while GCW was 2043±791 mmHg%. 14 (5%) patients were classified as Stage 0, 61 (21%) as Stage 1, 128 (44%) as Stage 2, 15 (5%) as Stage 3, and 71 (25%) as Stage 4. GCW showed a continuous decline through the AS Stages (from Stage 0-4: 2963±652 vs. 2154±652 vs. 2168±718 vs. 1988±969 vs. 1552±772 mmHg%; p&amp;lt;0.001). Using univariate Cox analysis GCW (HR 0.968 [95% CI 0.938-0.998] per 100 unit change; p=0.034) and AS Staging (HR 1.236 [95% CI 1.015-1.505]; p=0.035) were both associated with all-cause mortality, while EF (HR 0.984 [95% CI 0.966-1.002]; p=0.085) and GLS (HR 1.042 [95% CI 0.984-1.103]; p=0.160) were not. In multivariate Cox regression models, both GCW (HR 0.957 [95% CI 0.922-0.992] per 100 unit change; p=0.018) and AS cardiac damage staging (HR 1.263 [95% CI 1.029-1.549]; p=0.025) were proven to be significant independent predictors of all-cause mortality. In TAVR patients, preoperative GCW values exhibited a persistent decrease across AS Stages. As opposed to EF and GLS, GCW and AS Staging both showed strong association with all-cause mortality in our cohort. Moreover, GCW had higher prognostic value than any other conventional or advanced measure of LV function.

Estimated transmitral E- and A-wave overlapping predicted prognosis in patient with heart failure with preserved ejection

Abstract Background The impact of heart rate (HR) variability on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not fully understood. Variations in HR may affect transmitral blood flow and consequently left ventricular filling and left atrial pressure. Changes in HR can cause the transmitral E-wave and A-wave to merge at higher HRs, while their interval lengthens at slower HRs (Figure: left). A recent study (Izumida. ESC Heart Fail. 2020;7:3231) demonstrated that the degree of overlap or interval between E- and A-waves can be estimated using resting HR and the deceleration time of the E-wave (DcT) on Doppler echocardiography. Purpose This study aims to investigate the relationship between the estimated overlap length between E- and A-waves and prognosis in patients with HFpEF. Methods Echocardiography was performed before hospital discharge in 398 patients (80±9 years, 59.0% female) hospitalized for decompensated HFpEF who were registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry. The overlap length between E- and A waves was estimated using the formula [6.2 × HR (bpm) + 0.81 × DcT (ms) -589 (ms)] as previously described (a negative value means distance between two waves). Patients were divided into four groups based on quartiles of overlap length (Q1 to Q4, with Q4 representing the highest overlap length) and followed for a median duration of 759 days (interquartile range: 370, 1107 days) to observe all-cause mortality. Results The estimated overlap length in the study patients was -167±85 ms, and 105 deaths occurred during follow-up. The overlap length was selected as an independent predictor for all-cause mortality by Cox proportional hazards regression analysis (p=0.04), whereas HR or DcT was not. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure: Right, p=0.02 by log-rank test), and the Q4 group (335 to -123ms) showed significantly higher mortality than the Q2 (-124 to -173 ms, p=0.03). Conclusion The overlap length of E and A predicted mortality in HFpEF patients, and the presence of overlap or shorter interval were associated with higher mortality. Optimal HR based on overlap length may be a new target for HFpEF therapy.Figure 1

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.

The prognostic utility of troponin T levels in patients undergoing PCI during initial hospitalisation for STEMI

Abstract The prognostic utility of presentation or "peak" high-sensitivity troponin T (hsTnT) levels following ST-segment elevation myocardial infarction (STEMI) has been previously reported, but hsTnT, unlike other bio-markers of myocyte damage, have a 2nd or ‘plateau-phase’ of release which lasts over a week. We have reported correlations between plateau-phase hsTnT levels, and cardiac MRI determined infarct size, though whether these levels are more highly associated with late mortality than "peak" (or highest) levels, needs clarification. Methods Hence we determined late mortality and the combination of cardiovascular death, myocardial infarction and cerebrovascular accident [CD/MI/CVA] among patients with STEMI, and an HsTnT level &amp;gt;36 hours after symptom onset (plateau phase), who underwent percutaneous coronary intervention (PCI), either primary or pharmaco-invasive, during initial hospitalisation between October 2003 and December 2021. HsTnT levels and other potential prognostic factors were determined. Results Amongst 1955 patients, 119 patients (6%) had died by 2 years and 192 (10%) patients experienced CD/MI/Stroke. The highest quartile of plateau phase hsTnT levels (³ 3786 ng/L ng/L), were more highly associated with 2-year mortality, than the highest quartile of "peak" hsTnT levels (³ 7687 ng/L ng/L). The Figure shows Peak and plateau hs-TnT levels in quartile groups were assessed by rank test to obtain p-values. Patients lost to follow-up or with less than 2-years of follow up were considered censored. Peak quartile 1; hs-TnT £ 1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L. Log rank mortality analyses are shown in the Figure. Peak quartile 1; hs-TnT &amp;lt;1611 ng/L, peak quartile 2; hs-TnT 1612 – 3900 ng/L, peak quartile 3; hs-TnT 3901 – 7686 ng/L; peak quartile 4; hs-TnT ³ 7687 ng/L. Plateau quartile 1; hs-TnT £ 1060 ng/L, plateau quartile 2; hs-TnT 1061 – 2135 ng/L; plateau quartile 3; hs-cTnT 2136 – 3785 ng/L, plateau quartile 4; hs-TnT &amp;gt;3786 ng/L. Multivariate Cox regression analysis incorporating age, sex, smoking status, hypertension, renal function, cardiogenic shock and heart failure hospitalisation found plateau hs-TnT levels (HR, 3.564; 95% CI, 1.674 – 7.590; P = 0.001) were an independent predictor of all-cause mortality at 2-years post-STEMI, whereas peak hs-cTnT levels (HR, 1.965; 95% CI, 0.959 – 4.025; P = 0.065) were not. Conclusions Plateau phase hsTnT levels were of prognostic significance in STEMI patients treated with PCI. Thus, measurement of plateau hs-cTnT levels following STEMI could be an accurate, inexpensive method of long-term prognostic risk stratification.

Echocardiographic evaluation of right ventricle to pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis

Abstract Background Right Ventricle to Pulmonary Artery (RV/PA) uncoupling, which depicts the inability of RV contractility to match the increasing RV afterload, has recently gained recognition as a simple echocardiography parameter to aid prognosis judgment in patients with RV dysfunction. In Aortic Stenosis (AS) patients, the extent of RV dysfunction and Pulmonary Hypertension (PH) has been linked with poor outcomes, but the prognostic value of RV/PA uncoupling in AS patients undergoing TAVI has not been well-defined. Purpose To investigate the prognostic value of RV/PA uncoupling and its association with echocardiographic parameters in AS patients undergoing TAVI. Methods We conducted a systematic search through Pubmed and Embase to include studies up to February 2024. Studies were eligible if they evaluated the prognostic performance of RV/PA uncoupling in AS patients undergoing TAVI. Random-effects model were employed to pool the adjusted Hazard Ratio (aHR) with inverse-variance weighting method or Relative Risk (RR) with 95% Confidence Interval (95% CI) using Mantel-Haenszel test for categorical outcomes or Weighted Mean Difference (WMD) for numerical outcomes. Risk of bias assessment was conducted using the Newcastle Ottawa Scale (NOS). Results Thirteen studies were included. Out of 4,146 patients, 55.21% were reported to have RV-PA uncoupling prior to TAVI. RV/PA uncoupling was customarily assessed with TAPSE/PASP ratio, with threshold for uncoupling ranging between &amp;lt;0.31–&amp;lt;0.63 mm/mmHg. Follow-up period ranged between 6–65 months. Patients with baseline RV/PA uncoupling had lower LVEF (WMD -9.94% [-4.36– -15.53%]; I2 = 78%), lower TAPSE (WMD -4.98 mm [95% CI -1.15– -8.80]; I2 = 95%), and higher PASP (WMD 19.77 [95% CI 17.02–22.51]; I2 = 0%) compared to patients with RV/PA coupling at baseline. Baseline RV-PA uncoupling was an independent predictor of all-cause mortality (pooled aHR = 2.26 (95% CI 1.36–3.76); I2 = 77%) and composite endpoint of mortality and adverse cardiac or cerebrovascular events (pooled aHR = 2.07 (1.30–3.29); I2 = 24%). However, RV/PA uncoupling was not significantly associated with a higher risk of permanent pacemaker implantation after TAVI (pooled Risk Ratio 1.02 [0.70–1.47]; I2 = 0%). Conclusion Pre-procedural RV/PA uncoupling emerges as an independent predictor of worse prognosis in AS patients undergoing TAVI, contributing to a better understanding of the impact of this parameter on patient outcomes.

Computed tomography-derived myocardial extracellular volume as a prognosis predictor in patients with severe aortic stenosis

Abstract Background Patients with severe aortic stenosis (AS) face a higher risk of mortality, but prognosis is still heterogeneous and tools for prioritizing intervention are needed. Myocardial extracellular volume (ECV), measured non-invasively in pre-TAVR computed tomography (CT), is a marker of fibrosis that may reflect the degree of irreversible damage. The aim of this study was to assess the prognostic value of CT- derived ECV (ECVCT) in patients with severe AS referred for TAVR-planning CT. Methods Consecutive patients with severe symptomatic AS undergoing TAVR-planning CT between April and December 2022 at single centre were prospectively included. CT was performed on a 192-slice dual-source 3rdgeneration scanner. ECVCT was acquired during TAVR-planning using an additional post-contrast low-radiation-dose prospective acquisition. ECVCT was calculated as the ratio of change in CT attenuation (Hounsfield units [HU]) of the septal myocardium and the left ventricle (LV) blood pool before and after contrast administration, according to the equation: ECVCT = (1 – hematocrit) x (DHUmyo/DHUblood) – Figure 1A. The primary endpoint was all-cause mortality. The secondary endpoint was a composite endpoint including all-cause mortality and heart failure hospitalization. Results A total of 138 patients were included (mean age 81 ± 7 years; 46% male; mean transaortic gradient 51 ± 15 mmHg; mean aortic valvearea 0.75 ± 0.19 cm2; mean LV ejection fraction (EF) by 2D echocardiogram 57 ± 11%). No patient had a clinical diagnosis of cardiac amyloidosis. Mean ECVCT was 33.9 ± 8.0%. During a median follow-up period of 386 days (IQR 332 – 464), there were 18 deaths (13%), 13 before intervention and 5 after intervention; the secondary endpoint occurred in 26 patients (19%), 17 of which before intervention and 9 after. Patients who attained the primary endpoint were significantly older [81 ± 7 vs. 85 ± 7 years, P = 0.011], had lower left ventricular ejection fraction [51 ± 11 vs. 58 ± 11%, P = 0.015], higher NTproBNP levels [4739 (IQR 2003 – 9970) vs. 751 (IQR 314 – 2541), P &amp;lt;0.001] and higher ECV values (39.9 ± 7.4% vs. 33.0 ± 7.7%, P &amp;lt;0.001). After adjustment for age, LVEF and NTproBNP levels, ECVCT remained an independent predictor of all-cause mortality (adjusted HR 1.09 per 1% ECV increase, 95%CI 1.02 – 1.17, p=0.005 – Figure 1B) and also the secondary endpoint (adjusted HR 1.07 per 1% ECV increase, 95%CI 1.01 – 1.13, p=0.002). Conclusions In this prospective observational cohort study, interstitial fibrosis assessed by CT-derived ECV was associated with poor outcomes in patients with severe AS. ECVCT values may be useful to identify a subgroup of patients with higher risk who may benefit from earlier intervention.

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&amp;lt;0.001), CV death (HR 2.07, 95%CI 1.56-2.74, p&amp;lt;0.001), and all-cause mortality (HR 1.93, 95%CI 1.59-2.34, p&amp;lt;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.

Right atrial and ventricular function in risk stratification of patients with pulmonary artery hypertension

Abstract Background Right atrial (RA) phasic function was proved to be impaired in individuals with pulmonary arterial hypertension (PAH), the awareness of the nonnegligible involvement of RA in the clinical course of PAH was raised. However, evidence for the clinical significance of the RA strain in prognostication and risk stratification for PAH patients was limited. Method Participants diagnosed with PAH from June 2013 to December 2022 in West China Hospital were prospectively and continuously recruited. The primary endpoint was all-cause mortality, and the second endpoint was a combination of all-cause mortality and heart failure-related repeat hospitalization. Cox regression analysis and Kaplan Meier survival analysis were performed to identify the association between variables and outcomes. C-index, 1-year mortality, and annual event rate were performed to confirm the value of RA strain in PAH patients’ risk stratification. Result A total of 283 participants (mean age, 38 ± 14 years, 84 male) were finally included, following a median follow-up duration of 31.5 months (interquartile range: 15.1-53.9 months). Significant decreases in RA reservoir (p&amp;lt;.001), conduit (p&amp;lt;.001), booster pump function (p&amp;lt;.001), right ventricular global longitudinal strain (RVGLS, p&amp;lt;.001), and free-wall longitudinal strain (RV-FWLS, p&amp;lt;.001) were observed in participants with all-cause mortality than those who survived. Using 16.1% and 23.6% as thresholds for RA reservoir strain, PAH patients could be divided into low-, intermediate, and high-risk groups well, with calculated 1-year mortality of 1.8%, 6.9%, and 21.4%. Moreover, RA reservoir strain presented with better 1-year mortality predictive performance than RV-FWLS (C-index, 0.82 [0.72-0.92] vs 0.72 [0.62-0.82], p&amp;lt;.001). The addition of RA reservoir strain had significantly increased the power of both REVEAL Lite2 and Comparative, Prospective Registry of Newly initiated Therapies for Pulmonary Hypertension (COMPERA) models (both p&amp;lt;.001). Conclusion RA reservoir strain was an independent predictor of all-cause mortality in individuals with pulmonary arterial hypertension and could be used to stratify participants into different risk stratification stratum.

Prognostic impact of the extent of coronary artery disease in patients with acute transmural myocardial infarction undergoing complete percutaneous revascularization

Abstract Background The management of acute myocardial infarction has been revolutionised by the introduction of early coronary angiography and the reperfusion strategies. Recent studies support the standard of care of complete myocardial revascularization in all patients with ST-elevation myocardial infarction (STEMI) without assessing the prognostic role of the extent of coronary artery disease (CAD). Purpose To evaluate whether the extent of CAD in patients with STEMI has a prognostic impact independent of complete myocardial revascularization. Methods Observational cohort study of 365 patients with STEMI who underwent complete revascularization. For each patient the extent of CAD has been quantified using Gensini Score (GS), which takes into account both the severity and location of the lesions. The primary endpoint of the study was all-cause mortality, while cardiovascular mortality and a composite of major adverse cardiovascular events (MACE: cardiovascular mortality, recurrent acute myocardial infarction or myocardial revascularization and stroke) were defined as secondary endpoints. To assess the prognostic role of GS in predicting all-cause mortality, the area under the curve (AUC) was calculated. The best cut-off was determined as the one that maximized Youden's index (sensitivity + specificity - 1). Results Patients with a GS &amp;gt;80, indicating extensive coronary disease, had significantly higher rates of both cardiovascular [4 (16.7%) vs. 12 (3.5%); p = 0.002] and all-cause mortality [5 (20.8%) vs. 24 (7%); p = 0.016], than those with a GS ≤80. A GS &amp;gt;80 was demonstrated to be an independent predictor of all-cause mortality [hazard ratio = 5; 95% confidence interval: 1.5-16.8; p = 0.01] Conclusions The Gensini Score can identify high-risk patients with STEMI who may benefit from more intensive therapies to improve prognosis, although current guidelines do not specify treatment based on the extent of coronary disease.Long-term outcomes according to GSPrognostic value of GS

Elevated mitral valve pressure gradient following transcatheter edge-to-edge repair is independently associated with inferior outcomes in atrial, but not in ventricular secondary mitral regurgitation

Abstract Background In transcatheter mitral valve edge-to-edge repair (M-TEER), the goal of optimizing post-procedural residual mitral regurgitation inadvertently carries the risk of generating relevant mitral stenosis, resulting in an elevated mean mitral valve pressure gradient (MPG). In patients with primary mitral regurgitation, an elevated post-procedural MPG has been found to independently predict impaired outcomes. However, the effect of elevated post-procedural MPG on outcome after M-TEER in patients with secondary mitral regurgitation (SMR) has yet to be fully elucidated. This study investigated the impact of elevated MPG on outcome in the EuroSMR registry, a large, multi-center real-world cohort of patients with SMR. Methods This retrospective study included patients who underwent M-TEER for SMR between 2009 and 2021 in 12 centers. Patients were stratified into two groups based on SMR etiology: (1) ventricular SMR (vSMR), and (2) atrial SMR (aSMR). The etiology was considered as vSMR in patients with a left ventricular ejection fraction (LV-EF) &amp;lt;50% and aSMR in subjects with preserved left ventricular function (LV-EF ≥50%) and a markedly dilated left atrium (Left Atrial Volume Index [LAVi] ≥40ml/m2). According to the proposed M-VARC threshold, post-procedural MPG was assessed by discharge transthoracic echocardiography and was considered elevated if &amp;gt;5 mmHg. The primary endpoint was all-cause mortality after 5 years, with statistical analysis conducted using Kaplan-Meier and uni- and multivariable Cox Regression analysis. Results Among the 1703 patients in the study (vSMR: n=1420; aSMR: n=283), elevated post-procedural MPG was observed in 9.4% (n=133) of vSMR and 19.1% (n=54) of aSMR patients. Atrial fibrillation was significantly more prevalent in aSMR (78.4% vs. 57.1%, p&amp;lt;0.001). Patients with vSMR had a higher median surgical risk assessed by the EuroScore II (aSMR vs. vSMR: 7.0% [IQR 4.0, 13.1] vs. 4.9% [IQR 2.9, 8.5], p&amp;lt;0.001). Kaplan-Meier analyses for all-cause mortality after 5 years demonstrated significant differences in aSMR patients (low vs. elevated MPG: 48.9% vs. 69.8%, log-rank p&amp;lt;0.01), while there was no difference in vSMR patients (55.7% vs. 60.8%, log-rank p=0.66) (Figure 1). This observed effect remained significant even after accounting for common confounding factors: elevated MPG was an independent predictor for all-cause mortality in aSMR patients (HR=1.86; 95%-CI: 1.14-3.02, p=0.013) but not in vSMR patients (HR=1.00; 95%-CI: 0.74-1.35, p=0.99). Conclusion Our findings suggest that elevated post-procedural MPG is an independent predictor of adverse outcomes in patients with aSMR, but not in those with vSMR. This effect may partially be explained by a reduced left atrial function and higher rates of atrial fibrillation.Figure 1.Study flowchart

Cardiovascular magnetic resonance-derived left atrioventricular coupling index as a novel prognostic marker for light-chain amyloidosis

BackgroundLeft atrioventricular coupling index (LACI) is a novel biomarker, and the prognostic value of LACI to predict cardiovascular events has been validated. The present study aimed to explore the prognostic value of LACI in patients with light-chain (AL) amyloidosis. MethodsWe prospectively enrolled 179 patients with AL amyloidosis who underwent cardiovascular magnetic resonance imaging between December 2011 and January 2020. LACI was defined as the ratio between the left atrial volume and the left ventricular volume at end-diastole. The primary endpoint was all-cause mortality. Receiver operating characteristic curve was used to identify the optimal cut-off of LACI in predicting all-cause mortality. Univariable and multivariable Cox proportional hazard models were used to assess the association of LACI and primary endpoint. ResultsDuring a median follow-up of 30 months, 118 (65.9 %) patients with all-cause mortality were documented. LACI was significantly higher in patients with primary endpoint compared to those without primary endpoint (55.4 %, interquartile range: 31.6 %–71.5 % vs. 39.4 %, interquartile range: 24.1 %–54.7 %, p = 0.001). The optimal cut-off for LACI to predict mortality was 49.3 %. In multivariate Cox regression analysis, LACI≥49.3 % (HR 1.907, 95 % CI 1.273–2.857, p = 0.002) was an independent predictor of all-cause mortality. On Kaplan-Meier analysis, patients at advanced Mayo stage (IIIa and IIIb) can be further risk stratified using LACI≥49.3 % (log-rank p = 0.035, p = 0.025). ConclusionThe LACI provides powerful independent prognostic value in AL amyloidosis. The LACI has incremental prognostic value to predict all-cause mortality over the Mayo stage in patients at the advanced Mayo stage.

The value of D-dimer-albumin ratio as a prognostic biomarker in critically ill patients with sepsis: A retrospective single-center study

BackgroundThis study aimed to examine the potential prognostic significance of the D-dimer-albumin ratio (DAR) in critically ill patients with sepsis. MethodsA retrospective cohort study was carried out at the Affiliated Hospital of Jiangsu University, involving 1123 patients diagnosed with sepsis from January 2015 to November 2023. The patients were categorized into four groups (Q1-Q4) based on their DAR levels. The primary outcomes measured were in-hospital mortality and ICU mortality. Survival analysis was conducted using Kaplan-Meier survival curves and the log-rank test. Additionally, Cox proportional hazards regression models were utilized to investigate the relationship between the DAR and all-cause mortality. ResultsThe study population had a median age of 75 years (interquartile range: 65–84), and the median DAR was 0.15 (interquartile range: 0.08–0.32). The rates of hospital mortality and ICU mortality were 33.7 % and 31.9 % respectively. There was an observed increase in the cumulative incidence of 30-/60-day mortality with higher DAR levels (log-rank test, P < 0.001). After accounting for other variables, the results from multivariable Cox proportional hazards analyses demonstrated that DAR independently predicted hospital death [HR (95%CI): 1.419 (1.205–1.670); P < 0.001] and ICU death [HR (95%CI): 1.437 (1.219–1.693); P < 0.001]. ConclusionsThe DAR was found to be an independent predictor of all-cause mortality in critically ill patients with sepsis.

Effect of impaired kidney function on outcomes and treatment effects of oral anticoagulant regimes in patients with atrial fibrillation in a real-world registry.

The impact of impaired kidney function on outcomes and treatment benefits of vitamin-K antagonists (VKA) versus direct oral anticoagulants (DOAC) in patients with atrial fibrillation (AF) has insufficiently been investigated in randomized controlled studies (RCTs). Most studies and registries are either biased due to incomplete enrolment of consecutive patients in large pharma industry sponsored registries, or due to short recruitment periods or incomplete assessment of important variables in national registries. This study uses data from the Heidelberg Registry of Atrial Fibrillation (HERA-FIB), a retrospective single-center registry of 10,222 consecutive patients with AF presenting to the emergency department of University Hospital of Heidelberg from June 2009 until March 2020. Rates of all-cause mortality, stroke, major bleeding and myocardial infarction (MI) were related to the presence and severity of impaired presenting kidney function, as well as to assigned treatment with VKA vs. DOAC. The risks for all-cause mortality (HR: 3.26, p<0.001), stroke (HR: 1.58, p<0.001), major bleeding (HR: 2.28, p<0.001) and MI (HR: 2.48, p<0.001) were significantly higher in patients with an eGFR<60 ml/min at admission and increased with decreasing eGFR. After adjustment for variables of CHA2DS2VASc-score, presence of eGFR <60 ml/min remained as an independent predictor for all-cause mortality, major bleeding and MI. The hazard ratio (HR) for all-cause mortality, major bleedings and MI was significantly lower in patients receiving DOAC compared to VKA. Findings from our large real-life registry confirm the data from RCTs and extend our knowledge on the effectiveness and safety of DOACs to subjects that were underrepresented in RCTs.

Prognostic Value of Shock Index Creatinine in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement

Introduction: Shock index (SI) and its derivatives have been reported to have prognostic value in various cardiovascular diseases. This study aims to ascertain the utility of shock index creatinine (SIC) in predicting mid-term mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods: We conducted a retrospective analysis of 555 patients with severe AS who underwent TAVR from April 2016 to March 2023. SIC was calculated as (SI × 100) – estimated creatinine clearance (CCr). The primary endpoint was all-cause mortality during the follow-up period, and secondary endpoints included in-hospital complications as defined by the Valve Academic Research Consortium-3 (VARC-3) criteria. Patients were stratified into two groups based on the optimal cutoff value determined by the receiver-operating characteristic (ROC) curve. Cox regression analysis was employed to identify independent predictors of all-cause mortality. Additionally, restricted cubic spline (RCS) was deployed to illustrate the relationship between SIC and mortality risk. The predictive performance of risk scores was evaluated using the area under the ROC curve (AUC). Results: Over a mean follow-up period of 21.5 months, there were 51 cases of all-cause mortality. Patients with a high SIC, identified by a cutoff of 16.5, exhibited a significantly higher cumulative all-cause mortality compared to those with a low SIC (18.3% vs. 5.2%, p < 0.001; adjusted HR = 2.188; 95% CI 1.103–4.341, p = 0.025). Patients with a high SIC were older (p = 0.002) and exhibited a higher prevalence of frailty (p < 0.001). Furthermore, they exhibited a heightened probability of moderate or severe mitral regurgitation (p < 0.001), tricuspid regurgitation (p < 0.001), and pulmonary hypertension (p < 0.001) compared to those with a low SIC. In terms of perioperative complications, acute kidney injury (10.1% vs. 3.9%, p = 0.008) and bleeding (13.6% vs. 6.7%, p = 0.014) were more prevalent in patients with a high SIC. The RCS demonstrated a positive correlation between SIC and all-cause mortality rate. Furthermore, incorporating high SIC into the STS score improved its predictive value for 1-year all-cause mortality (AUC: 0.731 vs. 0.649, p = 0.01). Conclusion: Patients with a high SIC are more likely to experience frailty and cardiac damage and exhibit an increased in-hospital and mid-term mortality rate. SIC may provide additional information for risk stratification of patients undergoing TAVR.