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.

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.

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.

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< 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< 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.

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).

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.

Left appendage closure after intracranial hemorrhage: safety, efficacy and timing

Abstract Background Oral anticoagulation (OAC) use increases the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF). Left atrial appendage occlusion (LAAO) is an alternative to OAC, however data about its use in patients with prior ICH is scare and the timing of its performance is controversial. Furthermore, the long-term outcomes in this group of patients have not been described. Objective To evaluate the safety and efficacy of LAAO in patients with non-valvular AF and prior ICH (CHA2SVASc &amp;gt;2) and to determine adequate timing of its performance. Methods The sample was obtained from a cohort of 397 patients with AF in which LAAO was performed between 2009 and 2020. In 115 of these patients, the indication for this procedure was ICH (29.8 %). Patients were divided into two groups: early occlusion (n=68; 59%), in which the procedure was performed before 90 days had elapsed after the bleeding, and late occlusion (n=47; 41%), after 90 days. Results Procedure success was 97% globally. Annual incidence of ischemic events was of 0,6%, with an absolute risk reduction of 5,9% and relative risk reduction of 90,3% compared to the predicted risk by CHA2DS2-VASC score. Regarding major hemorrhagic events, annual incidence was of 4%, with an absolute risk reduction of 3,4% and relative risk reduction of 45% compared to the predicted risk by HASBLED score. There were no significant differences between the procedures performed in patients with history of intracranial bleeding and other indications for the procedure. Early closure (first 90 days after the intracranial hemorrhage) was as safe as late closure, without an increase in in-hospital bleedings or complications. Furthermore, long-term follow-up demonstrated a significant reduction in all-cause mortality (11.76% versus 46.8%; HR 0.2, IC95% 0.07-0.55; p&amp;lt;0.001). compared with late occlusion. Conclusions Left atrial appendage occlusion is an effective and safe treatment option to reduce the risk of ischemic stroke in selected patients with AF patients and history of ICH over mean follow-up of 3 years. Early occlusion seems to be at least as safe and effective as late occlusion and therefore could potentially reduce the rate of complications after ICH in selected patients.Survival and closure timingIschemic and bleeding risk reduction

Abstract 14588: Comparison of Different Antithrombotic Regimens After Left Atrial Appendage Occlusion: A Systematic Review and Network Meta-Analysis

Background: The optimal antithrombotic therapy following left atrial appendage occlusion (LAAO) in patients with non-valvular atrial fibrillation (AF) remains uncertain, given the high-risk profile of this population. This network meta-analysis aimed to compare the efficacy and safety of various antithrombotic strategies after LAAO. Methods: We conducted a comprehensive search of MEDLINE, Cochrane, Embase, Lilacs, and ClinicalTrials.gov databases for studies that reported clinical outcomes after LAAO, categorized by the antithrombotic therapies administered at discharge. Direct oral anticoagulants (DOACs), vitamin-K antagonists (VKAs), single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), DOAC plus SAPT, VKA plus SAPT, and no therapy were analyzed. We performed a frequentist random-effects network meta-analysis to estimate the odds ratio (OR) with 95% confidence intervals (CI) for each strategy. The surface under the cumulative ranking curve (SUCRA) P-scores provided a ranking of treatments. Quality assessment and risk of bias were conducted in accordance with Cochrane recommendations. Results: 39 observational studies and 1 clinical trial with a total of 11,111 patients with non-valvular AF were included, totaling 540 cardiovascular events. In the network comparison, DAPT (OR 0.35; 95% CI 0.16-0.76), DOAC (OR 0.35; 95% CI 0.13-0.94), DOAC plus SAPT (OR 0.17; 95% CI 0.04-0.74), and VKA (OR 0.34; 95% CI 0.12-0.97) were superior to no therapy to prevent device-related thrombosis (DRT), whereas SAPT (OR 0.46; 95% CI 0.21-1.03) and VKA plus SAPT (OR 0.43; 95% CI 0.10-0.87) were similar to no antithrombotic therapy. DOAC was associated with a significant reduction of all-cause mortality compared with VKA (OR 0.36; 95% CI 0.15-0.85) and a non-significant trend vs. SAPT (OR 0.49; 95% CI 0.22-1.11). Moreover, DAPT (OR 0.49; 95% CI 0.26-0.91) was superior to SAPT in reducing thromboembolic events, but similar to VKA (OR 0.88; 95% CI 0.37-2.37). There was no significant difference between therapies analyzed in the occurrence of major bleeding. Conclusion: In patients with nonvalvular AF undergoing LAAO, DOAC monotherapy is safe and reduce DRT, all-cause mortality, and thromboembolic events compared with other therapies.

Combined telemonitoring and telecoaching for heart failure improves outcome

Telemedicine has been shown to improve the outcome of heart failure (HF) patients in addition to medical and device therapy. We investigate the effectiveness of a comprehensive telehealth programme in patients with recent hospitalisation for HF on subsequent HF hospitalisations and mortality compared to usual care in a real-world setting. The telehealth programme consists of daily remote telemonitoring of HF signs/symptoms and regular individualised telecoaching sessions. Between January 2018 and September 2020, 119,715 patients of a German health insurer were hospitalised for HF and were eligible for participation in the programme. Finally, 6065 HF patients at high risk for re-hospitalisation were enroled. Participants were retrospectively compared to a propensity score matched usual care group (n = 6065). Median follow-up was 442 days (IQR 309–681). Data from the health insurer was used to evaluate outcomes. After one year, the number of hospitalisations for HF (17.9 vs. 21.8 per 100 patient years, p < 0.001), all-cause hospitalisations (129.0 vs. 133.2 per 100 patient years, p = 0.015), and the respective days spent in hospital (2.0 vs. 2.6 days per year, p < 0.001, and 12.0 vs. 13.4, p < 0.001, respectively) were significantly lower in the telehealth than in the usual care group. Moreover, participation in the telehealth programme was related to a significant reduction in all-cause mortality compared to usual care (5.8 vs. 11.0 %, p < 0.001). In a real-life setting of ambulatory HF patients at high risk for re-hospitalisation, participation in a comprehensive telehealth programme was related to a reduction of HF hospitalisations and all-cause mortality compared to usual care.