Significant Reduction In All-cause Mortality Research Articles

Impact of SGLT2 Inhibitors on Very Elderly Population with Heart Failure with Reduce Ejection Fraction: Real Life Data.

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19-0.82]) and glomerular filtration rate (HR 0.98 [0.98-0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16-0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study.

The role of day-case thoracoscopy at a district general hospital: A real world observational study

ObjectiveTo assess the feasibility and safety of talc pleurodesis performed as part of day-case medical thoracoscopy. MethodsA Richard Wolf® 5 mm mini thoracoscope through a 5.5 mm port was used with eligible cases having talc poudrage followed by insertion of indwelling pleural catheter (IPC). District nurses drain the IPC daily for the first 5 days. Once the drain output is <150 mL, the frequency is progressively reduced to once weekly. The drain is removed after two consecutive dry taps 1 week apart. ResultsOverall, 51 patients underwent day-case thoracoscopy. Median time to removal of IPC for our day-case protocol was 14 days. There were seven deaths within 70 days among 41 patients with malignant pleural effusion in the day-case cohort, compared to eight deaths in the 33 conventional thoracoscopy controls. Overall, the day-case cohort observed a statistically significant reduction in all-cause mortality at 180 days compared to the conventional cohort (log rank p = 0.024). The average cost per patient of the day-case and inpatient cohort was £1,328.0 ± 106.0 and £1,835.0 ± 295.0 (p = 0.961). ConclusionThis study suggests that thoracoscopy and talc poudrage can be performed safely as a day-case procedure. Further data are needed to ascertain long-term outcomes.

Examining the influence of Covid-19 restrictions, a nurse strike, and SARS-CoV-2 coinfection on bacteremia mortality: A Danish population-based cohort study (2019–2022)

ObjectivesBacteremia is an acute severe infection with high mortality. Changes in healthcare services and coinfections with SARS-CoV-2 may have affected the mortality for bacteremia during the COVID-19 pandemic, which has been reported for other major diseases. In this study we examine the all-cause bacteremia mortality amidst the COVID-19 pandemic. MethodsA population-based cohort study comprised of laboratory confirmed bacteremia episodes in the Capital Region, Denmark (March 2019–February 2022). Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % confidence intervals (CI) for all-cause bacteremia mortality associated with the Covid-19 restriction period, a strike period, and coinfection with SARS-CoV-2, adjusted for possible confounders. ResultsA total of 14,912 bacteremia episodes were identified in 12,693 patients during the study period. The 30- and 90-day all-cause mortality were 19 % and 27 %, respectively. The fully adjusted HR for 30- and 90-day all-cause mortality associated with the Covid-19 restriction period were 0.91 (95 % CI, 0.84 to 0.99) and 0.90 (95 % CI, 0.84 to 0.96), respectively, compared to the remaining time period. The corresponding HRs associated with SARS-CoV-2 coinfection were 1.29 (95 % CI, 1.11 to 1.50) and 1.36 (95 % CI, 1.20 to 1.55) compared to patients without coinfection. The association between the national nurse strike and all-cause bacteremia mortality was inconclusive. ConclusionsIn this large population-based cohort study, a significant reduction in all-cause mortality for bacteremia was observed during the Covid-19 restriction period in Denmark, while coinfection with SARS-CoV-2 seem to be a substantial risk factor for all-cause bacteremia mortality.

Association of physical activity and socio-economic status on mortality in older adults: a retrospective cohort study of KNHANES-mortality linked data

We examined the joint association of physical activity (PA) and socio-economic status (SES) on all-causes and cardiovascular disease (CVD) mortality in 6945 elderly Koreans (mean age: 71.6 years, 41.8% male) using data from the Korean National Health and Nutrition Examination Survey (2007–2013) and death data from Statistics Korea (2019). The SES included household income and education level. PA was assessed using the IPAQ and categorized according to the 2018 PA Guidelines. In stratified analyses using Cox proportional hazards by SES adherence to PA guidelines those who low household income group was associated with a reduced risk of all-cause mortality and CVD mortality, while in the lowest educational level group, it was associated with a reduced risk of all-cause mortality and CVD mortality. In the joint analysis, PA was associated with a significant reduction in all-cause mortality in all groups when compared with those who did not meet PA those who had the lowest SES. However, PA with CVD mortality risk was not significantly associated in the ‘upper-middle’ income and ‘high school’ education groups. The study revealed that PA significantly association mortality, particularly among older adults with low SES. This finding suggests the potential for targeted government interventions to promote healthy aging.

A 10-year review of presentation, management and outcomes of STEMI in a high-volume regional tertiary Australian centre

ObjectiveTo assess the trends and impact of changes in management of ST Elevation Myocardial Infarction (STEMI) from 2010 to 2019. DesignRetrospective analysis of data from STEMI hospitalisations including demographic, comorbidity, angiographic and outcome data. Setting/participantsHigh-volume non-surgical regional Australian tertiary referral centre. Main outcome measurementsIndex & 12-month mortality (all-cause & cardiovascular), door-to-balloon time, target-vessel failure, target-vessel revascularisation & procedure-related bleeding. ResultsFrom 2010 to 2019, 1299 patients presented with STEMI. The cardiovascular risk factor profile did not significantly change over the 10-year study period, p = 0.23. There was a significant trend toward culprit vessel percutaneous coronary intervention with stenting, rather than balloon angioplasty followed by surgical revascularisation, p = 0.029. The mean door-to-balloon time was 88 +/− 5.7 min and demonstrated a statistically significant improvement across the decade, p = 0.035. Radial access became the preferred angiographic approach (2010 92% femoral, 2019 91% radial). Drug-eluting stents (DES) replaced bare metal stent use. There was a statistically significant reduction in 12-month cardiovascular mortality across the decade (p = 0.042). However index hospitalisation (cardiovascular and all-cause) and 12-month all-cause mortality did not reduce. Young patients and women are important sub-groups of STEMI presentations with different risk factor profile. ConclusionsAdvances in management of STEMI such as radial access, use of DES and a significant reduction in door-to-balloon time across the decade resulted in a reduction of 12-month cardiovascular mortality over the decade however there was no significant reduction in 12-month all-cause mortality, or index hospitalisation cardiovascular or index hospitalisation all-cause mortality. Further research is needed to ensure non-mortality outcomes, such as heart failure hospitalisation and quality of life, also demonstrate temporal improvement with STEMI management advances. Earlier cardiovascular risk assessment should be considered in smokers than is currently recommended in Australian guidelines (≥45yo for most individuals).

Association between urate-lowering therapy initiation and all-cause mortality in patients with type 2 diabetes and asymptomatic hyperuricemia

AimsTo assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). MethodsThis nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. ResultsAmong 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71–0.84), CV mortality (HR 0.86; 95% CI, 0.76–0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64–0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360–420 μmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 μmol/L (HR 0.74; 95% CI, 0.59–0.94) while levels ≤360 μmol/L did not (HR, 0.96; 95% CI, 0.81–1.14), suggesting a U-shaped relationship. ConclusionsInitiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360–420 μmol/L could potentially enhance this reduced mortality.

Dampak Oforektomi terhadap Kualitas Hidup dan Fungsi Seksual Orang dengan Kanker Payudara

This study aims to identify the impact of orthorectomy on breast cancer patients, especially on their quality of life and sexual function. We conducted a systematic review adhering to PRISMA guidelines, searching articles from PubMed, ProQuest, Embase, and ScienceDirect databases from inception to March 2024. The search terms used were "oophorectomy", "quality of life", "sexual function", and "breast cancer". Results from 8 articles showed that oophorectomy can negatively affect quality of life, especially in physical and psychosocial aspects, and can be associated with sexual dysfunction. Ophorectomy was also associated with significant reductions in all-cause mortality and breast cancer-specific mortality. In conclusion, this study shows about ooforectomy have a significant impact on quality of life and sexual function of women, especially on physical and psychosocial aspects. Although, these impacts do not entirely affect quality of life, Keywords: Oophorectomy, Breast Cancer, Quality of Life, Sexual Dysfunction

Abstract PO5-15-10: Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096)

Abstract INTRODUCTION: Despite the development and validation of multimarker gene panels like OncotypeDx®, Mammaprint® and EndoPredict®, an affordable and globally accessible biomarker approach that can predict increased risk of all-cause mortality in patients diagnosed with ER+LN- breast cancer, as well as the efficacy of adjuvant endocrine + chemotherapy in mitigating such elevated risk, continues to be an unmet medical need. Lack of such a pragmatic solution continues to be the cause of preventable recurrent/metastatic disease in patients diagnosed with ER+LN- breast cancer in resource-challenged settings around the world. We hypothesized that a predictive biomarker strategy that measures expression of the plasticity marker FOXC1, in combination with clinical parameters like tumor size (TS) and tumor grade (TG), may offer equivalent results to that of the above multimarker gene panels at a significantly lower economic cost without compromising accuracy of prediction results. METHODS: Pre-treatment tumor RNA data obtained from a training cohort (compendium of gene expression microarray datasets, n=2857) and a single large validation cohort (SCAN-B Prospective Multicenter Observational Study, n=3520) for patients diagnosed with ER+LN- breast cancer were analyzed for FOXC1 expression, tumor size (TS) and tumor grade (TG) and correlated with Recurrence-Free Survival (RFS) and Overall Survival (OS). Optimized biomarker cutoff values based on model area-under-curve were leave-one-out cross validated and Risk-of-Recurrence (ROR) prediction algorithm derived utilizing the (compendium) training dataset. The unmodified strategy was then validated in the independent (SCAN-B) validation dataset. RESULTS: A predetermined High ROR score calculated using FOXC1 expression, TS and TG (trained using the compendium dataset) predicted efficacy of adjuvant endocrine + chemotherapy over that of adjuvant endocrine therapy alone in ER+LN- patients in terms of statistically significant reduction in all-cause mortality at 8-years post-diagnosis in the SCAN-B validation dataset (4.66% vs 24.06%, n=326, OR=6.48, 95%CI [2.97-14.11], p&amp;lt; 0.0001). OncotypeDx® (5.7% vs 14.4%, n=762, OR=2.79, 95%CI [1.37-5.67], p=0.002), Mammaprint® (5.1% vs 18.4%, n=665, OR= 95%CI [2.04-8.43], p&amp;lt; 0.0001) and Endopredict® (4.8% vs 15.2%, n=923, OR=3.58 95%CI [1.78-7.21], p=0.0002) were also statistically significant predictors of the same. CONCLUSION: Pre-treatment tumor FOXC1 mRNA or protein expression (assessed using qRT-PCR or routine immunohistochemistry (IHC), respectively, when combined with TS and TG presents a unique and economical alternative solution to multimarker gene panel tests like OncotypeDx®, Mammaprint® or Endopredict®, for guiding therapy of patients diagnosed with ER+LN- breast cancer in resource challenged settings. Such an approach to identify elevated risk of recurrence in patients diagnosed with ER+LN- breast cancer and prevent the same by guiding adjuvant endocrine + chemotherapy decisions, could help to extend recurrence-free and overall survival. Such an approach merits testing in real world ER+LN- patient cohorts in resource-challenged settings to help support implementation of this FOXC1-driven predictive biomarker strategy in the clinic. Citation Format: Partha Ray, Tania Ray, Clive Taylor, Robert Hussa. Plasticity marker FOXC1 expression accurately predicts efficacy of Adjuvant Tamoxifen + Chemotherapy in reducing all-cause mortality in ER+LN- Breast Cancer: Validation in the SCAN-B Prospective Study (NCT02306096) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-15-10.

AI-enabled electrocardiography alert intervention and all-cause mortality: a pragmatic randomized clinical trial.

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 .

Improved all-cause mortality with left bundle branch area pacing compared to biventricular pacing in cardiac resynchronization therapy: a meta-analysis.

Left bundle branch area pacing (LBBAP) has emerged as a physiological alternative pacing strategy to biventricular pacing (BIVP) in cardiac resynchronization therapy (CRT). We aimed to assess the impact of LBBAP vs. BIVP on all-cause mortality and heart failure (HF)-related hospitalization in patients undergoing CRT. Studies comparing LBBAP and BIVP for CRT in patients with HF with reduced left ventricular ejection fraction (LVEF) were included. The coprimary outcomes were all-cause mortality and HF-related hospitalization. Secondary outcomes included procedural and fluoroscopy time, change in QRS duration, and change in LVEF. Thirteen studies (12 observational and 1 RCT, n = 3239; LBBAP = 1338 and BIVP = 1901) with a mean follow-up duration of 25.8months were included. Compared to BIVP, LBBAP was associated with a significant absolute risk reduction of 3.2% in all-cause mortality (9.3% vs 12.5%, RR 0.7, 95% CI 0.57-0.86, p < 0.001) and an 8.2% reduction in HF-related hospitalization (11.3% vs 19.5%, RR 0.6, 95% CI 0.5-0.71, p < 0.00001). LBBAP also resulted in reductions in procedural time (mean weighted difference- 23.2min, 95% CI - 42.9 to - 3.6, p = 0.02) and fluoroscopy time (- 8.6min, 95% CI - 12.5 to - 4.7, p < 0.001) as well as a significant reduction in QRS duration (mean weighted difference:- 25.3ms, 95% CI - 30.9 to - 19.8, p < 0.00001) and a greater improvement in LVEF of 5.1% (95% CI 4.4-5.8, p < 0.001) compared to BIVP in the studies that reported these outcomes. In this meta-analysis, LBBAP was associated with a significant reduction in all-cause mortality as well as HF-related hospitalization when compared to BIVP. Additional data from large RCTs is warranted to corroborate these promising findings.

Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.

Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.

Mitral Valve Repair on Patients with Chronic Kidney Disease: Long Term Outcomes and Cardiac Remodelling

Objectives: Literature examining mitral valve repair (MVr) outcomes on CKD patients is largely limited to short term outcomes and percutaneous approaches. This study is the first to present long-term outcomes of mortality and morbidity with paired cardiac remodelling data on CKD patients undergoing surgical MVr.Design: A retrospective, observational, comparative study.Setting: Single-center university hospital.Participants: Patients with varying stages of CKD undergoing MVr from 2004-2018.Interventions: Patients were grouped by estimated glomerular filtration (eGFR) rate and followed for a maximum of 15 years. Long term outcomes and measures of cardiac remodelling were then compared between the groups.Measurements and Main Results: The primary outcome was all-cause mortality. Secondary outcomes included measures of postoperative morbidity and cardiac remodelling. Every 10 unit increase in eGFR was associated with a significant reduction in all-cause mortality at 5 years (HR 0.81 95% CI 0.67-0.98) p=0.028), 10 years (HR 0.82 CI 0.72-0.94 p=0.004), and at 15 years (HR 0.78 CI 0.69-0.88 p<0.001) Moderate CKD group had a significantly higher rates of all-cause mortality at 15 years (HR 3.38 CI 1.28-8.98 p=0.014). eGFR was a significant predictor for residual moderate to severe mitral regurgitation (MR) at 1 year (HR 0.74 CI 0.57-0.96 p=0.024). There was positive cardiac remodelling following MVr for CKD patients with significant reduction in LV size and LA volume.Conclusions: In patients with CKD undergoing MVr, eGFR is a predictor of decreased long-term survival and residual MR at 1 year. Further investigation is required for optimizing postoperative outcomes in this patient population.

Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations

Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined. To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation. In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023. Self-reported bilateral oophorectomy (with or without salpingectomy). All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality. There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy. In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

Sodium-Glucose Cotransport Protein 2 Inhibitors in Patients With Type 2 Diabetes and Acute Kidney Disease

Sodium-glucose cotransport protein 2 inhibitors (SGLT-2is) have demonstrated associations with positive kidney-related and cardiovascular outcomes in patients with type 2 diabetes. However, the association of SGLT-2is with outcomes among patients with type 2 diabetes and acute kidney disease (AKD) remains unclear. To examine the long-term associations of SGLT-2is with mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes and AKD. This cohort study used global health care data (the TriNetX database) spanning from September 30, 2002, to September 30, 2022. Propensity score matching was used to select a cohort of patients, and follow-up was conducted with a maximum duration of 5 years (completed on September 30, 2022) or until the occurrence of an outcome or death. The use of SGLT-2is. The primary outcomes measured were mortality, MAKEs, and MACEs. Adjusted hazard ratios (AHR) with 95% CIs were calculated to compare the risks between SGLT-2i users and nonusers, representing the mean treatment effect among the treated patients. A total of 230 366 patients with AKD (mean [SD] age, 67.1 [16.4] years; 51.8% men and 48.2% women) were enrolled in the study, which had a median follow-up duration of 2.3 (IQR, 1.2-3.5) years. Among these, 5319 individuals (2.3%) were identified as SGLT-2i users. Among nonusers, the incidence of mortality was 18.7%, the incidence of MAKEs was 21.0%, and the incidence of MACEs was 25.8%. After propensity score matching, the absolute differences between SGLT-2i users and nonusers for incidence of mortality, MAKEs, and MACEs were 9.7%, 11.5%, and 12.3%, respectively. Based on the treated population, SGLT-2i use was associated with a significantly lower risk of mortality (AHR, 0.69 [95% CI, 0.62-0.77]), MAKEs (AHR, 0.62 [95% CI, 0.56-0.69]), and MACEs (AHR, 0.75 [95% CI, 0.65-0.88]) compared with nonuse. External validation using a multicenter cohort data set of 1233 patients with AKD patients who were SGLT-2i users confirmed the observed beneficial outcomes. Notably, the risk reduction associated with SGLT-2is remained significant even among patients without hypertension, those with advanced chronic kidney disease, and those not receiving other hypoglycemic agents. In this cohort study of patients with type 2 diabetes and AKD, administration of SGLT-2is was associated with a significant reduction in all-cause mortality, MAKEs, and MACEs when compared with nonuse, underscoring the importance of SGLT-2is in care after acute kidney injury. These findings emphasize the potential benefits of SGLT-2is in managing AKD and mitigating the risks of major cardiovascular and kidney diseases.

The impact of extracorporeal membrane oxygenation on mortality in patients with cardiogenic shock post-acute myocardial infarction: a systematic review and meta-analysis.

Cardiogenic shock remains the leading cause of death in patients hospitalized with acute myocardial infarction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in the treatment of infarct-related cardiogenic shock. However, there is limited evidence regarding its beneficial impact on mortality. The aim of this study was to systematically review studies reporting the impact of VA-ECMO on mortality in patients with acute myocardial infarction complicated by cardiogenic shock. A comprehensive search of medical databases (Cochrane Register and PubMed) was conducted. Studies that reported mortality outcomes in patients treated with VA-ECMO for infarct-related cardiogenic shock were included. The database search yielded 1194 results, of which 11 studies were included in the systematic review. Four of these studies, with a total of 586 patients, were randomized controlled trials and were included in the meta-analysis. This demonstrated that there was no significant difference in 30-day all-cause mortality with the use of VA-ECMO compared with standard medical therapy [odds ratio (OR) 0.91; 95% confidence interval (CI) 0.65-1.27]. Meta-analysis of two studies showed that VA-ECMO was associated with a significant reduction in 12-month all-cause mortality (OR 0.31; 95% CI 0.11-0.86). Qualitative synthesis of the observational studies showed that age, serum creatinine, serum lactate, and successful revascularization are independent predictors of mortality. Veno-arterial extracorporeal membrane oxygenation does not improve 30-day all-cause mortality in patients with cardiogenic shock following acute myocardial infarction; however, there may be significant reduction in all-cause mortality at 12 months. Further studies are needed to delineate the potential benefit of VA-ECMO in long-term outcomes. The protocol was registered in the PROSPERO International Prospective Register of Systematic Reviews (ID: CRD42023461740).

Effectiveness of Cardiac Rehabilitation Services in Low- and Middle-Income Countries: A Systematic Review.

Cardiac rehabilitation (CR) is a cost-effective intervention that can reduce cardiovascular disease (CVD) morbidity and mortality by 20%. Despite the clear benefits of CR, it remains unavailable and underutilized. This study aimed to assess the effectiveness of different CR models in reducing CVD-related morbidity and mortality in low-and middle-income countries. We conducted a systematic review of studies conducted in low- and middle-income countries that assessed at least one of the three phases of CR (inpatient rehabilitation, outpatient rehabilitation in a hospital, or community setting and maintenance). The primary outcomes of interest were mortality (all-cause and CVD-specific), CVD-related morbidity, functional capacity, risk factor reduction, and quality of life (QoL). The electronic search retrieved 1,102 studies, of which 22 were retrieved and included in the review. These studies were conducted between 2011 and 2022 and the majority (18) were conducted in Asia. All studies except one were randomized controlled trials (RCTs), and all except one were conducted at a single site. The target population in most studies (16) included patients with coronary artery disease (CAD). Seven studies have incorporated digital technology. Only one study has reported a significant reduction in all-cause mortality. Thirteen studies reported data on functional capacity, and 16 on quality of life (QoL), showing statistically significant improvements. Data on risk factors, anxiety, and depression have shown mixed results. CR is effective in low- and middle-income countries, and strategies to scale it up using locally available resources tailored to the patient population should be adopted.

Are sarcopenia and its individual components linked to all-cause mortality in heart failure? A systematic review and meta-analysis

Abstract Objective The objective of this systematic review and meta-analysis was to assess sarcopenia and its components as prognostic factors in patients with heart failure (HF). Methods From inception to December 2022, a systematic literature search was carried out utilizing PubMed, Web of Science, Scopus, and Cochrane Library databases. A meta-analysis employing a random-effects model was performed to assess the pooled effects. Results The systematic review and meta-analysis included 32 and 18 longitudinal studies, respectively. The prediction of 1- to 2-year all-cause mortality in sarcopenia was not statistically significant (hazard ratio (HR): 1.35, 95% CI 0.76–2.38, I2 = 54%, P = 0.31). The lowest combined quartile and quantile of the population were used to define low handgrip strength that showed identical results (HR: 1.24, 95% CI 0.94–1.62, I2 = 0%, P = 0.13). Low L3-L4 psoas muscle mass (HR: 2.20, 95% CI 1.26–3.83, I2 = 87%, P &lt; 0.01) and slow gait speed (HR: 1.45, 95% CI 1.20–1.74, I2 = 0%, P &lt; 0.01) were significant contributors to all-cause mortality risk. Additionally, a 0.1 m/s increase in gait speed demonstrated a significant reduction of all-cause mortality (HR: 0.77, 95% CI 0.66–0.90, I2 = 60%, P &lt; 0.01). Our narrative synthesis also described appendicular lean mass (ALM) and short physical performance battery (SPPB) scores as significant prognostic factors. Conclusions Compared to patients with higher overall functional performance, those with HF and low ALM, low psoas muscle mass, low SPPB, and slow gait speed are at an increased risk of all-cause mortality. Early prevention and/or treatment of lower limb physical function deterioration may be an essential strategy to reduce the risk of premature death in HF. Graphical abstract

Prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis

BackgroundThe prolonged β-lactam antibiotics infusion has been an attractive strategy in severe infections, because it provides a more stable free drug concentration and a longer duration of free drug concentration above the minimum inhibitory concentration (MIC). We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of prolonged vs intermittent intravenous infusion of β-lactam antibiotics for patients with sepsis.MethodsThis study was prospectively registered on PROSPERO database (CRD42023447692). We searched EMBASE, PubMed, and Cochrane Library to identify eligible studies (up to July 6, 2023). Any study meeting the inclusion and exclusion criteria would be included. The primary outcome was all-cause mortality within 30 days. Two authors independently screened studies and extracted data. When the I2 values < 50%, we used fixed-effect mode. Otherwise, the random effects model was used. TSA was also performed to search for the possibility of false-positive (type I error) or false-negative (type II error) results.ResultsA total of 4355 studies were identified in our search, and nine studies with 1762 patients were finally included. The pooled results showed that, compared with intermittent intravenous infusion, prolonged intravenous infusion of beta-lactam antibiotics resulted in a significant reduction in all-cause mortality within 30 days in patients with sepsis (RR 0.82; 95%CI 0.70–0.96; P = 0.01; TSA-adjusted CI 0.62–1.07). However, the certainty of the evidence was rated as low, and the TSA results suggested that more studies were needed to further confirm our conclusion. In addition, it is associated with lower hospital mortality, ICU mortality, and higher clinical cure. No significant reduction in 90-day mortality or the emergence of resistance bacteria was detected between the two groups.ConclusionsProlonged intravenous infusion of beta-lactam antibiotics in patients with sepsis was associated with short-term survival benefits and higher clinical cure. However, the TSA results suggested that more studies are needed to reach a definitive conclusion. In terms of long-term survival benefits, we could not show an improvement.

Effect of timely availability of TTR-stabilizing therapy on diagnosis, treatment initiation, and cardiovascular outcomes in transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin-stabilization reduces cardiovascular morbidity and mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Despite increased access, regional differences in the availability of therapy continue to exist, and how these may affect diagnostic efficacy and cardiovascular outcomes is currently unknown. Objective To determine how access to and availability of tafamidis affected time-to-diagnosis, time-to-therapy, and cardiovascular outcomes in patients with ATTR-CM. Methods and Results 91 consecutive patients diagnosed with ATTR-CM between June 2019 and June 2021 were evaluated for TTR-stabilizing therapy with tafamidis. Access was regulated by an expanded access program for the initial 42 patients (early cohort; 46.2%), while insurance coverage was required for the latter 49 patients (facilitated access cohort, 53.8%) after local regulatory drug approval in April 2020. Tafamidis was started in 37 of 42 (88.1%), and 43 of 49 patients (87.8%), respectively. Baseline characteristics, e.g., age (76.3±6.4 vs. 77.3±6, p = 0.45), sex (male: 95.2% vs. 93.9%) and ATTR-CM disease stage (≤stage 2: 88.2% vs. 90.9%, p= 0.919) were comparable between both groups. Timely availability of tafamidis after April 2020 numerically reduced time from first presentation to diagnosis (median [months (IQR)]) from 6.2 (1.3;28.9) to 2.4 (0.7; 21.7) months (p = 0.196) and from presentation to therapy from 24.4 (10.7;46.8) to 11.8 (6.4; 32.4) months (p = 0.127). While RV function assessed by echocardiography significantly decreased in the early cohort between diagnosis and therapy initiation (S’ velocity 10±2.2 to 9.2±2.2 cm/s; p = 0.018; TAPSE 17.3±4.7 to 15.7±3.9, p = 0.008) it remained stable in the facilitated access cohort (S’ velocity 9.56±2.57 to 9.36±2.28 cm/s; p = 0.83; TAPSE 15.6±4.2 to 16.3±3.1, p = 0.45). After a median follow-up 42.3 and 24.9 months in the early and facilitated access cohort, respectively, timely availability of tafamidis in the facilitated access cohort was associated with a significant reduction of annual heart failure hospitalisations (treated: 0.12±0.34 vs. 0.5±1, p = 0.049; overall cohort: 0.17±0.37 vs. 0.35±0.47, p = 0.044). Overall, timely diagnosis of ATTR-CM within 12 months of first presentation was associated with a significant reduction in all-cause mortality [HR = 3.490 (95% CI 1.37 to 8.91), p = 0.009], prolonged survival without MACE [HR = 2.50 (95% CI 1.30 to 4.81), p = 0.006] or heart failure hospitalisation [HR = 2.52 (95% CI 1.24 to 5.16), p = 0.011]. Conclusions Availability of tafamidis numerically shortened time-to-diagnosis and time-to-therapy initiation in ATTR-CM patients. Timely diagnosis and initiation of therapy was associated with a reduction in all-cause mortality and heart failure hospitalisations.Door-to-diagnosis-therapyClinical outcomes

Direct oral anticoagulants versus vitamin k antagonists in patients with atrial fibrillation and bioprosthesis: a systematic review and meta-analysis

Abstract Background/Introduction The large randomized clinical trials published to date have shown that direct oral anticoagulants (DOACs) are as or more effective than vitamin K antagonists (VKAs) in the prevention of thromboembolic events in atrial fibrillation (AF) and generally show a better bleeding risk profile. However, patients with bioprosthetic valves have been underrepresented in RCTs. The aim of this study was to assess the safety and efficacy of DOAC in patients with AF and bioprosthetic valves through a systematic review and meta-analysis including recent evidence from comparative cohort studies and real-world results. Methods A systematic review of the scientific literature and a subsequent meta-analysis were carried out. We included RCTs or comparative observational studies, published from January 2017 to January 2022 comparing DOACs versus vitamin K antagonists in patients with AF or atrial flutter and bioprostheses. We collected data of all-cause mortality, major bleeding, and systemic embolism. The primary outcome of interest was all-cause mortality. Secondary outcomes were systemic embolism or stroke. The primary safety outcome was major bleeding. Results Our analysis included 12 studies, 4 RCTs and 8 observational studies that enrolled a total of 30.283 patients. All-cause mortality 6 observational and 3 RCT were combined. A 9% reduction was found for all-cause mortality in patients treated with DOACs (HR,0.91; P=.0068;95%CI,0.85–0.97;I2=8%). Stroke and systemic embolism 4 RCT and 8 observational studies were combined. No evidence showing a significant effect of DOAC therapy on risk reduction for stroke and embolism was obtained (HR, 0.87; P =.29; 95%CI, 0.67–1.14; I2=45%). Major bleeding The results of the 12 studies were combined. A robustness analysis was performed, and the ENVISAGE RCT was identified as atypical. We therefore proceeded to re-run the meta-analysis without this study’s results. The overall effect size was HR, 0.79 (P = .0001; 95%CI, 0.73-0.85; I2 = 0%), with a 21.1% reduction of major bleeding with DOAC therapy compared with VKA. The present study has several limitations. It has the inherent limitations of the studies included and the combination of findings from comparative observational cohort studies and ad hoc studies from RCTs, which entails a potential source of bias. Second, individual risks for each type of bioprosthesis were not studied. Finally, the four currently marketed DOACs were included in our meta-analysis, but their efficacy and safety were not evaluated separately. Conclusions Our study found that DOAC therapy is associated with a significant reduction of all-cause mortality with no significant increase in the risk of systemic embolism or stroke. This reduction could be attributed to a decrease in major bleeding. Our results therefore suggest that DOACs could be a safer alternative than VKAs in this group of patients.