One-year Mortality In Patients Research Articles

The Impact of Previously Diagnosed Depression on Early and One-Year Mortality in Patients with Acute Ischemic Stroke in Opole Province, Poland

Background: Depression is a known stroke risk factor, but its influence on stroke course depending on gender and age is not clearly defined. The purpose of this study was to determine the impact of previously diagnosed depression on early and one-year mortality in patients with acute ischemic stroke (IS) in relation to gender, age, and concomitant diseases. Methods: This study was based on the registry created from the public health insurer in Poland (2009–2020). Two groups were distinguished: IS-D—patients with IS and a diagnosis of depression within preceding 5 years (n = 520); IS-nD—patients with IS who had never been diagnosed with depression (n = 11,505). Results: In-hospital, 30-day, and 1-year mortality did not differ between groups (3.8% vs. 5.1%, 13.1% vs. 12.9%, and 27.1% vs. 26.8%, respectively). However, when statistical analysis was performed stratified by gender and age, we found a significantly higher 30-day and 1-year mortality in men under the age of 65 with previously diagnosed depression in comparison to those without depression (13.6% vs. 3.8%, p < 0.001; and 20.3% vs. 10.8, p < 0.021, respectively). Conclusions: The incidence of post-stroke depression was higher in IS-D group, regardless of gender and age. Early and one-year mortality was higher in younger men with IS and previously diagnosed depression.

Prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in patients admitted with acute heart failure

Abstract Introduction The inflammatory marker, soluble urokinase plasminogen activator receptor (suPAR), has emerged as a promising prognostic biomarker of heart failure (HF). Higher levels of suPAR in plasma are indicative of hospital readmissions and mortality. Currently little is known about suPAR-values upon admission in patients with acute heart failure (AHF). Purpose This study investigates the prevalence of elevated suPAR and prognostic value in patients hospitalized with AHF. Methods In this prospective cohort study, all patients ≥ 18 years old admitted at the Emergency Department at a large University Hospital in Denmark, were consecutively included from March 10, 2020, to March 31, 2022. The follow-up period was 365 days. The biomarker suPAR was measured in all patients upon admission (median time from admission to suPAR measurement was two hours (IQR 3: 3,9-6,9)). Patient data was extracted from the electronic patient record system, and a cardiologist adjudicated whether the patients had AHF. Patients were stratified according to validated cut-off values of suPAR above or below 6 ng/mL. Kaplan-Meier survival analysis and Cox Regression were used to assess the association between suPAR levels and one-year mortality outcomes. Results A total of 408 (5%) AHF patients, from a total population of 6,715, were included in the study. 40 patients were excluded due to missing suPAR-values and the final analysis comprised of 368 AHF patients. Among AHF patients upon admission, the mean suPAR value was 6.2 ng/mL (standard deviation [SD] = 4.8 ng/mL), and non-AHF patients had a mean value of 4.5 ng/mL (SD = 3.1 ng/mL). A suPAR level above 6 ng/mL was significantly associated with mortality (figure 1), log-rank test p-value < 0.0001. Furthermore, Cox regression analysis demonstrated that elevated suPAR levels were independently associated with increased risk of mortality with a hazard ratio (HR): 2.09 (95% CI: 1.59-2.90), p-value < 0.001 after adjusting for potential confounders: age, sex, atrial fibrillation, Chronic Obstructive Pulmonary Disease, and Creatinine levels. Conclusion The inflammatory biomarker suPAR measured upon hospital admission in AHF patients is significantly associated with one-year mortality in patients admitted with AHF. The potential of suPAR as a valuable prognostic marker in AHF is offering clinicians a tool to identify high-risk patients and tailor management strategies, accordingly, thereby improving patient outcomes.Figure 1 - 1 year mortality

Prevalence of multiple native valvular heart disease in TAVR patients: a multicenter study assessing the impact of staged transcatheter edge-to-edge repair

Abstract Background Multiple valvular heart disease (VHD) is associated with poor prognosis in patients undergoing TAVR. Existing research focuses either on mitral or tricuspid regurgitation (MR, TR), without providing comparative analysis of their long-term effects. Moreover, whether staged transcatheter edge-to-edge repair (TEER) improves outcomes in these patients is unknown. Purpose This multicenter study aimed to evaluate the prevalence of multiple VHD within a recent TAVR cohort and to assess and compare the impact of concomitant severe MR and TR on outcomes at both one and five years post-TAVR. Additionally, we aimed to examine the potential impact of staged TEER for severe VHD in patients treated with TAVR. Methods The study cohort consisted of 2,823 patients undergoing TAVR at our Heart Center between 2015 and 2022. This representative cohort was used to investigate the prevalence of multiple VHD in a contemporary TAVR population and to assess and compare the impact of severe MR and TR on outcomes following TAVR. Additionally, this cohort, along with TAVR cohorts from other Heart Centers, was screened for additional valvular intervention. Patients who underwent staged transcatheter edge-to-edge repair for severe MR (n=147) or TR (n=59) were included. Results A concomitant persistent severe VHD was observed in 369 (13.1%) patients, with 208 (7.4%) having a severe MR, and 161 (5.7%) having a severe TR. The one-year mortality was significantly higher in patients with a severe VHD compared to the overall cohort (9.0 vs 5.2 per 100 PY, p<0.01). Notably, the highest one-year mortality was observed in patients with severe TR (13.3 per 100 PY) followed by patients with severe MR (6.4 per 100 PY) and those with no or a mild VHD (3.9 per 100 PY, p<0.01). This difference persisted over five years, with mortality rates of 27.8 per 100 PY in TR patients compared to 16.7 and 10.6 per 100 PY in MR patients and those with no or a mild VHD (p<0.01), Figure 1A. The landmark analysis revealed lower one-year mortality in patients who underwent staged TEER compared to those with severe VHD (4.1 vs 12.1 per 100 PY, p<0.001). This trend continued at the five-year follow-up, with a mortality rate of 11.6 per 100 PY in the staged TEER group versus 25.8 per 100 PY in the group with severe VHD (p<0.001), Figure 1B. The multivariate analyses revealed that concomitant severe TR was independently associated with one-year mortality (HR: 1.75 [95% CI: 1.14 – 2.67], p<0.01). Conclusion A concomitant clinically significant VHD was prevalent among patients with AS undergoing TAVR. The persistence of severe VHD was associated with increased one- and five-year mortality following TAVR. Specifically, severe TR was associated with higher mortality rates compared to severe MR. The potential benefit of an additional staged TEER for concomitant VHD should be carefully considered, as it shows promise in improving outcomes for patients with persistent severe VHD after TAVR.

Comprehensive risk factor-based nomogram for predicting one-year mortality in patients with sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a frequent and severe complication in septic patients, characterized by diffuse brain dysfunction resulting from systemic inflammation. Accurate prediction of long-term mortality in these patients is critical for improving clinical outcomes and guiding treatment strategies. We conducted a retrospective cohort study using the MIMIC IV database to identify adult patients diagnosed with SAE. Patients were randomly divided into a training set (70%) and a validation set (30%). Least absolute shrinkage and selection operator regression and multivariate logistic regression were employed to identify significant predictors of 1-year mortality, which were then used to develop a prognostic nomogram. The model’s discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. A total of 3,882 SAE patients were included in the analysis. The nomogram demonstrated strong predictive performance with AUCs of 0.881 (95% CI: 0.865, 0.896) in the training set and 0.859 (95% CI: 0.830, 0.888) in the validation set. Calibration plots indicated good agreement between predicted and observed 1-year mortality rates. The decision curve analysis showed that the nomogram provided greater net benefit across a range of threshold probabilities compared to traditional scoring systems such as Glasgow Coma Scale and Sequential Organ Failure Assessment. Our study presents a robust and clinically applicable nomogram for predicting 1-year mortality in SAE patients. This tool offers superior predictive performance compared to existing severity scoring systems and has significant potential to enhance clinical decision-making and patient management in critical care settings.

The Effect of Sepsis Associated Encephalopathy on One-Year Mortality in Patients Aged 65 Years and Over After Discharge: A Retrospective Cohort Study

The Effect of Sepsis Associated Encephalopathy on One-Year Mortality in Patients Aged 65 Years and Over After Discharge: A Retrospective Cohort Study

The PROgnostic ModEl for chronic lung disease (PRO-MEL): development and temporal validation

BackgroundPatients with chronic lung diseases (CLDs), defined as progressive and life-limiting respiratory conditions, experience a heavy symptom burden as the conditions become more advanced, but palliative referral rates are low and late. Prognostic tools can help clinicians identify CLD patients at high risk of deterioration for needs assessments and referral to palliative care. As current prognostic tools may not generalize well across all CLD conditions, we aim to develop and validate a general model to predict one-year mortality in patients presenting with any CLD.MethodsA retrospective cohort study of patients with a CLD diagnosis at a public hospital from July 2016 to October 2017 was conducted. The outcome of interest was all-cause mortality within one-year of diagnosis. Potential prognostic factors were identified from reviews of prognostic studies in CLD, and data was extracted from electronic medical records. Missing data was imputed using multiple imputation by chained equations. Logistic regression models were developed using variable selection methods and validated in patients seen from January 2018 to December 2019. Discriminative ability, calibration and clinical usefulness of the model was assessed. Model coefficients and performance were pooled across all imputed datasets and reported.ResultsOf the 1000 patients, 122 (12.2%) died within one year. Patients had chronic obstructive pulmonary disease or emphysema (55%), bronchiectasis (38%), interstitial lung diseases (12%), or multiple diagnoses (6%). The model selected through forward stepwise variable selection had the highest AUC (0.77 (0.72–0.82)) and consisted of ten prognostic factors. The model AUC for the validation cohort was 0.75 (0.70, 0.81), and the calibration intercept and slope were − 0.14 (-0.54, 0.26) and 0.74 (0.53, 0.95) respectively. Classifying patients with a predicted risk of death exceeding 0.30 as high risk, the model would correctly identify 3 out 10 decedents and 9 of 10 survivors.ConclusionsWe developed and validated a prognostic model for one-year mortality in patients with CLD using routinely available administrative data. The model will support clinicians in identifying patients across various CLD etiologies who are at risk of deterioration for a basic palliative care assessment to identify unmet needs and trigger an early referral to palliative medicine.Trial registrationNot applicable (retrospective study).

Development of a risk score for predicting one-year mortality in patients with atrial fibrillation using XGBoost-assisted feature selection.

Development of a risk score for predicting one-year mortality in patients with atrial fibrillation using XGBoost-assisted feature selection.

Growth differentiation factor-15 and routine laboratory parameters are associated with one-year mortality in patients with end-stage heart failure undergoing heart transplantation evaluation.

Growth differentiation factor-15 (GDF-15) is a hormone that regulates inflammatory responses, tissue repair, and cardiac remodeling, the three key processes underlying the development and progression of heart failure (HF). Furthermore, GDF-15 integrates information from cardiac and extracardiac disease pathways that are linked to multiorgan dysfunction in advanced stages of HF. This study aimed to determine which factors are associated with one-year mortality in patients with end-stage HF, with particular emphasis on GDF-15. We prospectively analyzed 315 consecutive hospitalized patients with end-stage HF who underwent heart transplantation evaluation between 2018 and 2022. The endpoint was all-cause mortality during one-year follow-up. We measured routine laboratory parameters and the serum GDF-15 concentration using a sandwich enzyme-linked immunosorbent assay (ELISA) (SunRedBio Technology Co, Ltd, Shanghai, China). The median age of the patients was 57 (50-62) years. During follow-up, 97 patients died. Higher serum concentrations of GDF-15 (hazard ratio [HR], 1.119; 95% CI, 1.095-1.144; P <0.001), high-sensitivity C-reactive protein (HR, 1.140; 95% CI, 1.037-1.253; P = 0.006), fibrinogen (HR, 1.003; 95% CI, 1.001-1.005; P = 0.003), bilirubin (HR, 1.055; 95% CI, 1.027-1.084; P <0.001), N-terminal pro-B-type natriuretic peptide (HR, 1.342; 95% CI, 1.206-1.493; P <0.001), and gamma-glutamyl transpeptidase (HR, 1.007; 95% CI, 1.002-1.012; P = 0.003) were independently associated with one-year mortality. Higher GDF-15, high-sensitivity C-reactive protein, fibrinogen, bilirubin, gamma-glutamyl transpeptidase, and N-terminal pro-B-type natriuretic peptide concentrations were independently associated with worse survival in patients with end-stage HF.

Impact of capacity building and tele ECG based decision support on change in thrombolysis rate and inhospital and one year mortality in patients with STEMI, using hub and spoke model; multi-phasic intervention trial

BackgroundWe report the impact of capacity building and teleconsultation on change in the thrombolysis rates and one-year mortality in patients with STEMI using a hub and the spoke model of STEMI care. MethodsTwenty secondary care public hospitals were linked with a teaching hospital as a hub centre and the impact of the intervention on change in ischemic time, thrombolysis rates and all-cause in-hospital and one-year mortality was compared. Results29 patients with STEMI were treated during pre-intervention from April 2020 to June 2020 and 255 patients during the post-intervention period from July 2020 to Oct 2021 in spoke centres. 245 patients were reported to a hub centre during the study period. The thrombolysis rate was significantly higher in the spoke centres after intervention (65.5%vs. 27.5 % p < 0.001) and was also significantly higher than in patients treated in a hub centre (65.5 % vs. 45.7 % p < 0.01). The in-hospital mortality was significantly lower in patients treated at spoke centres compared to those treated at the hub centre (7.8 % vs. 15.5 % < 0.003). The significant difference in mortality rate continued at one year (11.0 % vs.18.4 % p < 0.01). The median time from symptoms to thrombolytic therapy was significantly lower in STEMI patients treated in spoke centres compared to a hub centre (230 min vs. 356 min p < 0.001). ConclusionThe hub and spoke model of STEMI care is effective in increasing thrombolysis rate, and decreasing in-hospital and one-year mortality rate.

Risk Factors for Therapeutic Failure and One-Year Mortality in Patients with Intramedullary Nail-Associated Infection after Trochanteric and Subtrochanteric Hip Fracture Repair.

Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric IM nail infection at a Spanish academic hospital during a 10-year period, with a minimum follow-up of 22 months. Of 4044 trochanteric and subtrochanteric IM nail implants, we identified 35 cases of infection during the study period (0.87%), 17 of which were chronic infections. Patients with therapeutic failure (n = 10) presented a higher average Charlson Comorbidity Index (CCI) (5.40 vs. 4.21, p 0.015, CI 0.26-2.13) and higher rates of polymicrobial (OR 5.70, p 0.033, CI 1.14-28.33) and multidrug-resistant (OR 7.00, p 0.027, CI 1.24-39.57) infections. Upon multivariate analysis, polymicrobial infection and the presence of multidrug-resistant pathogens were identified as independent risk factors for therapeutic failure. Implant retention was associated with an increased risk of failure in chronic infection and was found to be an independent risk factor for overall one-year mortality in the multivariate analysis. Our study highlights the importance of broad-spectrum empirical antibiotics as initial treatment of trochanteric and subtrochanteric IM nail-associated infection while awaiting microbiological results. It also provides initial evidence for the importance of implant removal in chronic IM-nail infection.

Predictive value of the systemic immune-inflammation index on one-year mortality in geriatric hip fractures.

Geriatric hip fractures are associated with a high incidence of mortality. This study examines the predictive value of the systemic immune-inflammation index (SII) on one-year mortality in elderly hip fracture patients. A single-center retrospective study was conducted between February 2017 and October 2020. Three hundred and eleven surgically treated consecutive hip fracture patients were included in the study. Admission, postoperative first day, and postoperative fifth-day SII values were calculated. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values, and patients were divided into high and low groups according to these cut-off values. After univariate Cox regression analysis, significant factors were included in the multivariate Cox proportional hazards model to adjust the effect of covariates and explore independent predictive factors associated with mortality. Further subgroup analysis was performed to evaluate the accuracy of the results for different clinical and biological characteristics. The mean age was 80.7 ± 8.0 years, and women made up the majority (67.8%) of the patients. The one-year mortality rate was 28.0%. After univariate and multivariate analyses, high postoperative fifth-day SII remained an independent predictor of one-year mortality (adjusted HR 2.16, 95% CI 1.38-3.38, p = 0.001). Older age, male gender, Charlson comorbidity index (CCI) ≥ 2, and hypoalbuminemia were found to be other independent predictors. The optimal cut-off value of the postoperative fifth-day SII was calculated at 1751.9 units (p < 0.001). The postoperative fifth-day SII is a simple and useful inflammatory biomarker for predicting one-year mortality in patients with hip fracture.

Association between Preoperative C-Reactive Protein-to-Albumin Ratio and Mortality after Plastic and Reconstructive Surgery.

Background: Prognostic markers have not been extensively studied in plastic and reconstructive surgery. Objective: We aimed to evaluate the prognostic value of preoperative C-reactive protein (CRP)-to-albumin ratio (CAR) in plastic and reconstructive surgery and to compare it with the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and modified Glasgow prognostic score (mGPS). Methods: From January 2011 to July 2019, we identified 2519 consecutive adult patients who were undergoing plastic and reconstructive surgery with available preoperative CRP and albumin levels. The receiver operating characteristic (ROC) curve was generated to evaluate predictability and estimate the threshold. The patients were divided according to this threshold, and the risk was compared. The primary outcome was one-year mortality, and the overall mortality was also analyzed. Results: The one-year mortality was 4.9%. The CAR showed an area under the ROC curve of 0.803, which was higher than those of NLR, PLR, and mGPS. According to the estimated threshold of 1.05, the patients were divided into two groups; 1585 (62.9%) were placed in the low group, and 934 (37.1%) were placed in the high group. After inverse probability weighting, the mortality rate during the first year after plastic and reconstructive surgery was significantly increased in the high group (1.3% vs. 10.9%; hazard ratio, 2.88; 95% confidence interval, 2.17-3.83; p < 0.001). Conclusions: In this study, high CAR was significantly associated with one-year mortality of patients after plastic and reconstructive surgery. Further studies are needed on prognostic markers in plastic and reconstructive surgery.

Ceruloplasmin, Catalase and Creatinine Concentrations Are Independently Associated with All-Cause Mortality in Patients with Advanced Heart Failure.

The role of oxidative/antioxidative system imbalances in advanced heart failure (HF) has not been fully investigated. The aim of this study was to identify factors associated with one-year mortality in patients with advanced HF, with particular emphasis on oxidative/antioxidative balance parameters. We analyzed 85 heart transplant candidates who were hospitalized at our institution for right heart catheterization. Ten milliliters of coronary sinus blood was collected to measure oxidative/antioxidative markers. The median age was 58 (50-62) years, and 90.6% of them were male. The one-year mortality rate was 40%. Multivariable logistic regression analysis revealed that ceruloplasmin (OR = 1.342 [1.019-1.770], p = 0.0363; per unit decrease), catalase (OR = 1.053 [1.014-1.093], p = 0.0076; per unit decrease), and creatinine (OR = 1.071 [1.002-1.144], p = 0.0422; per unit increase) were independently associated with one-year mortality. Ceruloplasmin, catalase, and creatinine had areas under the curve of 0.9296 [0.8738-0.9855], 0.9666 [0.9360-0.9971], and 0.7682 [0.6607-0.8756], respectively. Lower ceruloplasmin and catalase in the coronary sinus, as well as higher creatinine in peripheral blood, are independently associated with one-year mortality in patients with advanced HF. Catalase and ceruloplasmin have excellent prognostic power, and creatinine has acceptable prognostic power, allowing the distinction of one-year survivors from nonsurvivors.

The IFSD Score-A Practical Prognostic Model for Invasive Fungal Spondylodiscitis.

Objectives: Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. The previous literature revealed limited data concerning its outcomes. This study aimed to establish a risk-scoring system to predict the one-year mortality rate of this disease. Methods: A total of 53 patients from a multi-centered database in Taiwan were included in this study. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to one-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic (ROC) curve was used to express the performance of our IFSD scoring model. Results: Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or <0.4 103/µL, hemoglobin < 8 g/dL, and evidence of candidemia. One-year mortality rates for patients with IFSD scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the ROC curve was 0.823. Conclusions: We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of one-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

Surgical site infection after trochanteric and subtrochanteric fractures: a single centre retrospective analysis

Surgical site infection (SSI) following osteosynthesis of trochanteric or subtrochanteric fractures is a rare but serious complication with incidence rate ranging from 1 to 3%. SSIs are associated with higher mortality and increased length of hospital stay resulting in higher healthcare costs and loss of life quality. In this retrospective analysis all patients with SSI following osteosynthesis of trochanteric or subtrochanteric fractures at the Department of Trauma Surgery were identified. We included all surgical procedures performed from 1992 to 2018, using data from electronic health records and SSI-Trauma-Registry. The aim was to describe epidemiological data, as well as to identify parameters correlating with the occurrence of SSI and mortality. Of 2753 patients, 53 (1.9%) developed SSI. Longer operative time was demonstrated among patients with SSI (P = 0.008). Mortality during the first postoperative year was significantly higher in the SSI group (32.1% vs. 19.1%; P = 0.018), with detection of methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA; HR 4.13, CI 95% 1.24–13.80; P = 0.021) or Enterococcus spp. (HR 5.58, CI 95% 1.67–18.65; P = 0.005) being independent risk factors. Male sex (HR 2.25, 95% CI 1.86–2.73; P < 0.001) and higher mean age (HR 1.05, 95% CI 1.04–1.06; P < 0.001) were found to be predictors for 1-year mortality in non-infected patients. SSI rate was low with 1.9% and longer duration of surgery was associated with infection. Patients with SSI had a higher 1-year mortality, with detection of MSSA, MRSA and enterococci significantly increasing the risk of dying. Male sex and higher age were risk factors for one-year mortality in patients without SSI.

Clinical Risk Factors of Perioperative Pressure Injury in Older Adult Patients with a Hip Fracture.

To examine the clinical risk factors of perioperative pressure injury (PrI) in older adults with a hip fracture, including preoperative chronic comorbidities and postoperative complications. In this retrospective study, the authors queried the PearlDiver Patient Records database between January 2011 and January 2020. Data from 54,194 patients without preexisting PrI were included for analyses. Patients were separated into two groups: (1) one or more perioperative PrI and (2) no PrI. Clinical factors as outcome variables include 21 comorbidities and 10 complications. Univariate analyses were computed to compare the variables between groups, and two logistic regression models were developed to find comorbidity predictors and complication predictors. Of all patients, 1,362 (2.5%) developed one or more perioperative PrI. Patients with perioperative PrIs were more likely to be older men. One-year mortality for patients with perioperative PrI was 2.5 times that of patients without PrI. The regression models showed that predictors of perioperative PrI are malnutrition, hypoalbuminemia, frailty, peripheral vascular disease, dementia, urinary tract infection, perioperative red blood cell transfusion, and atrial fibrillation. Screening for these comorbidities and complications may assist in determining the risk of PrI in older adults undergoing hip fracture surgery. Determining PrI risk enables the appropriate prevention strategies to be applied perioperatively.

Serum levels of the endoplasmic-reticulum-stress chaperone GRP78 are associated with inflammation, identify patients with coronary artery disease and predict mortality

Abstract Introduction Endoplasmic-reticulum-stress (ER Stress) and associated chaperones like the ER-Stress moderator GRP78 (glucose-regulated-protein, 78kDa) are involved in the pathogenesis of coronary artery disease (CAD). In addition to their intracellular effects, secretion and extracellular properties of chaperones, including GRP78, were recently described. In a recent study using proteomic data, we found coronary endothelial cells to secrete GRP78 into the extracellular space. Here, we investigated the significance of serum GRP78 in patients undergoing coronary angiography for suspected CAD. Methods Serum concentration of GRP78 was measured by ELISA in an all-comers cohort of 789 patients with clinical indication for coronary angiography. Samples were drawn from the arterial sheath. CAD was defined as &amp;gt;50% stenosis in any major epicardial coronary artery. Patients were stratified according to their clinical presentation (CCS: chronic coronary syndrome or ACS). Clinical endpoint was all-cause mortality after one year. Patients with malignant or active auto-immune diseases were excluded. Results Mean age was 70.8 ± 11.9 years and 65% of patients were male. 24% patients presented with acute coronary syndrome (ACS). CAD was found in 72.4% of patients. Mean GRP78 serum concentration was 2492 ng/ml. Increased levels of GRP78 (&amp;gt; median) were associated with diabetes (29.9% vs. 23.1%, p = 0.03), a higher BMI (28.9 kg/m2 ± 7.1 vs. 27.0 kg/m2 ± 6.0, p &amp;lt; 0.0001) and chronic kidney disease (CKD: 23.3 % vs. 17.1 %, p = 0.03). There was no difference regarding age or sex. We further compared GRP78 levels to other biomarkers including WBC, Hemoglobin, Troponin, Creatinine, and Interleukin-6 (IL-6). There was no association between GRP78 levels and the mentioned biomarkers, except for a positive correlation between GRP78 and levels of Interleukin-6 (Pearson r =0.14, p = 0.004). GRP78 levels were increased in patients with CAD when compared to patients without CAD (2640 ng/ml vs. 2178 ng/ml, p = 0.013). Interestingly, GRP78 levels were lower in patients with ACS than in patients with CCS (2284 ng/ml vs. 2822 ng/ml, p = 0.018). There was no difference between NSTEMI and STEMI patients. Finally, we assessed prognostic relevance of GRP78 in patients with CAD. Increased GRP78 levels were associated with lower occurrence of the clinical endpoint of one-year mortality (5.3% vs. 10.6 % vs. p = 0.016). Increased GRP78 levels were associated with reduced one-year mortality (HR: 0.48 [95% CI: 0.25 - 0.92]). After adjusting for IL-6, age, sex, BMI, diabetes, CKD, and ACS, GRP78 remained an independent predictor of one-year mortality in patients with CAD. Conclusion GRP78 serum levels are generally elevated in patients with CAD but are downregulated during ACS. Reduced levels are associated with increased one-year mortality. These results support previous findings that GRP78 secretion is a protective mechanism in cardiovascular diseases.

Safety and efficacy of protamine administration for prevention of bleeding complications in patients with recent PCI undergoing TAVR

Abstract Background Despite major advances, TAVR is still associated with vascular and bleeding complications, that have an impact on mortality. Recent studies have shown that heparin antagonization using protamine resulted in lower bleeding rates in patients undergoing TAVR as compared to those without heparin reversal. However, there are only limited data on the safety of protamine regarding thromboembolic complications including in-stent thrombosis in TAVR patients who have had a recent PCI. Accordingly, daily practice varies between Centers. Purpose The aim of this multicentre study was to evaluate the safety and efficacy of protamine administration in patients who have had a recent PCI undergoing subsequent TAVR. Methods Our study included 1838 patients undergoing TAVI between 2017 and 2020. Of the patients included, 173 (9.4%) had a recent PCI (≤30 days), 319 (17.4%) had an intermediately (≥30 days) and 303 (16.5%) a previously performed PCI (≥6 months). Standardized vascular access management included the use of preclosure devices and PTA or implantation of a stent-graft, if necessary. The primary endpoint was a composite of one-year mortality and myocardial infarction at 30 days. Secondary endpoints included 30-day mortality and VARC-3-defined complications. Results The overall study population had a mean age of 81.1±6.2 years. Among patients with recent PCI, 134 (77.5%) patients received protamine for heparin reversal during the TAVR procedure. In the group of patients with intermediately and previously performed PCI 258 (80.9%) and 249 (82.2%) patients received protamine, respectively. In the recent PCI group, the occurrence of the primary endpoint was comparable between patients with protamine administration (24.6%) as compared to patients without heparin reversal (30.8%, p=0.53, Figure 1). Similarly, among patients with intermediately as well as previously performed PCI, the rates of the primary endpoint were comparable irrespective of protamine administration (20.1 vs 16.4%, p=0.59; 17.3 vs 27.7%, p=0.08, respectively, Figure 2). Moreover, among all three groups, the incidence of myocardial infarction at 30 days after TAVR was low and comparable between patients with and without heparin reversal (p&amp;gt;0.50). Overall, protamine administration was associated with decreased life-threatening bleeding (3.2 vs 9.4%, p&amp;lt;0.01) and major vascular complications (4.4 vs 7.9%, p=.02). Regarding safety endpoints, no overall differences were observed in the incidence of stroke between patients with and without protamine administration (1.5 vs 2.9%, p=0.13). Conclusion Protamine administration during the TAVR procedure did not increase the rate of myocardial infarction or one-year mortality in patients who have had a recently or intermediately performed PCI. Overall, heparin reversal using protamine resulted in significantly lower rates of life-threatening bleeding and major vascular complications, without increasing the incidence of stroke.Figure 1Figure 2

Impact of Persistent Medication Adherence and Compliance with Lifestyle Recommendations on Major Cardiovascular Events and One-Year Mortality in Patients with Type 2 Diabetes and Advanced Stages of Atherosclerosis: Results From a Prospective Cohort Study.

The aim of this study was to evaluate the impact of single and combined effects of persistent medication adherence and compliance with lifestyle recommendations on the incidence of major adverse cardiovascular events (MACE) and one-year all-cause mortality in patients with type 2 diabetes (T2D) and peripheral artery disease (PAD) after partial foot amputation (PFA), representing a unique cohort of patients with advanced stages of atherosclerosis. This is a prospective cohort study of 785 consecutive patients (mean age 60.9 ± 9.1 years; 64.1% males). Medication adherence was evaluated by using the proportion of days covered (PDC) measure calculation and was defined as a PDC ≥80%. It derived as an average of PDCs of the following four classes of drugs: a) antidiabetics (oral hypoglycemic medications and/or insulin); b) ACEI or ARBs; c) Statins; d) antiplatelet drugs. Lifestyle compliance was defined as a PDC ≥80% comprising of PDCs of a) physical activity of ≥30 minutes per day; b) healthy nutrition and weight management; c) non-smoking. Cox proportional hazard models adjusted for confounders were used. Total all-cause mortality was 16.9% (n = 133) at one-year follow-up. After adjusting for confounders, compared to adherent/compliant patients (n = 432), non-adherent and/or non-compliant patients had an increased risk of one-year mortality: HR = 8.67 (95% CI [5.29, 14.86] in non-adherent/non-compliant patients (n = 184), p < 0.001; HR = 3.81 (95% CI [2.03, 7.12], p < 0.001) in adherent/non-compliant patients (n = 101) and HR = 3.14 (95% CI [1.52, 6.45] p = 0.002) in non-adherent/compliant patients (n = 184). The incidence of MACE followed similar pattern (HR = 9.66 (95% CI [6.55, 14.25] for non-adherence/non-compliance; HR = 3.48 (95% CI [2.09, 5.77] and HR = 3.35 (95% CI [1.89, 5.91], p < 0.001 for single adherence or compliance. Medication adherence and compliance to lifestyle recommendations have shown to be equally effective to reduce the incidence of MACE and one-year mortality in patients with diabetes and PAD after PFA representing a population with highly advanced stages of atherosclerotic disease. Our findings underline the necessity to give lifestyle intervention programs a high priority and that costs for secondary prevention medications should be covered for patients under these circumstances. This study analyzed the single and combined effects of medication adherence and compliance with lifestyle recommendations on cardiovascular events and mortality in patients with type 2 diabetes and advances stages of atherosclerosis over a period of one year.Evaluation of medication adherence included antidiabetics, statins, dual antiplatelets and ACEI/ARBs, whereas lifestyle recommendations included healthy nutrition, physical activity and smoking cessation.Persistent medication adherence and lifestyle changes have shown to be equally effective to reduce the incidence of MACE and one-year mortality in patients representing a population with highly advanced stages of atherosclerotic disease, and positive effects added up to a double effect if patients were persistently adherent and compliant with both interventions.

Postoperative Outcomes and One-Year Mortality of Patients on Chronic Anticoagulation Medications Undergoing Infrainguinal Bypass

Patients requiring open infrainguinal bypass (IIB) frequently are taking chronic anticoagulation (AC) medications. Taking these medications in the preoperative setting may affect the outcomes of surgery. This study aims to evaluate postoperative outcomes and 1-year mortality of patients taking chronic AC medications that undergo IIB. Using data obtained from the Vascular Quality Initiative from January 2011 to October 2021, patients on warfarin or any direct oral anticoagulants (DOAC) within 30days of IIB were compared with patients not taking chronic AC medications. The primary outcomes were in-hospital, 30-day, and 1-year mortality. The secondary outcomes included total procedure time, need for perioperative packed red blood cell transfusion, prolonged length of hospital stay, postoperative myocardial infarction or stroke, and graft patency at discharge. A subgroup analysis was performed comparing patients taking warfarin with those taking DOACs. Univariate analyses and multivariate logistic regression, Kaplan Meier survival, and Cox regression analyses were used to analyze the data for postoperative and 1-year outcomes, respectively. A total of 55,076 patients underwent IIB during the study period, and 11,547 (20.97%) were on chronic AC prior to surgery. The 2 cohorts differed significantly in almost every demographic and clinical characteristic. Multivariate analyses adjusting for 45 potential confounders revealed that there was no significant difference in in-hospital, 30-day, and 1-year mortality. The total procedure time for the chronic AC cohort was on average 11.46±2.16min longer (P ≤ 0.001) and there was a greater risk of prolonged length of stay in the hospital (adjusted odds ratio [aOR]: 1.19, 95% confidence interval [CI]: 1.13-1.26, P<0.001). These patients also returned to the operating room (OR) at a greater rate (aOR: 1.12, 95% CI: 1.05-1.19; P=0.016) and demonstrated a significantly lower rate of graft patency at discharge (aOR: 0.73, 95% CI: 0.62-0.86, P=0.001). On subgroup analysis, multivariate analysis demonstrated lower 30-day mortality for the DOAC group in comparison to the warfarin group (aOR: 0.74, 95% CI: 0.57-0.94, P=0.015), but no significant differences in in-hospital and 1-year mortality. Patients taking AC medications within 30days prior to IIBs may require more perioperative red blood cell transfusions, longer hospitalizations, and return to the OR at a greater rate. They are also at an increased risk for loss of graft patency at discharge. However, these patients are not at increased risk of in-hospital, 30-day, or 1-year mortality. IIB can, therefore, be performed safely in patients taking chronic AC medications.