Risk Of All-cause Death Research Articles

Incremental prognostic value of late gadolinium enhancement granularity in patients with hypertrophic cardiomyopathy

Abstract Background The prognostic stratification of hypertrophic cardiomyopathy (HCM) using cardiac magnetic resonance (CMR) is based on the extent of late gadolinium enhancement (LGE). To enhance risk stratification for sudden cardiac death (SCD), the ESC has recently added LGE extent in the guidelines, at ≥15% of LV mass. However, SCD has become an uncommon event in this population, and mortality is now mostly related to other phenotypes, such as atrial fibrillation, stroke, and heart failure. While previous studies have showed the prognostic value of LGE to predict all-cause mortality, the prognostic impact of additional LGE features is not well established. Therefore, we aimed to assess the incremental prognostic value of the granularity of LGE including extent, location, and pattern in patients with HCM to predict all-cause death. Methods Between 2008 and 2021, all patients referred for HCM assessment using CMR, without history of coronary artery disease (CAD) or clinical history of myocarditis were prospectively recruited in two French centers. The outcome was all-cause death using the French National Registry of Death. The concept of "LGE granularity" was defined as a comprehensive model combining all the following LGE features with extent (by segment), location (septal or others), and pattern (midwall and/or subepicardial). Using nested Cox proportional hazard models, the additional predictive value of LGE features was assessed by the C-statistic increment, the continuous net reclassification improvement (NRI), the integrative discrimination index (IDI) and the global Chi-2. Results Among the 2,672 included patients (52±7 years, 56% males), 862 (32%) had LGE. After a median (IQR) follow-up of 9 (7–11) years, 447 (17%) patients died. Survival curves show an increased risk for LGE presence (log-rank p<0.001, Figure 1A). After adjustment for traditional prognosticators in the overall population (N=2,672), the presence of LGE was strongly associated with all-cause death (adjusted hazard ratio (HR) 3.96, 95% CI: 3.26-4.80, p<0.001). In the subgroup of patients with LGE (n=862), survival curves showed that all parameters defining the LGE granularity were associated with a higher risk of all-cause death (all p<0.001, Figure 1B). A nested Cox model adjusted on traditional prognosticators showed that the LGE extent, location and pattern were all independently associated with all-cause death (all p<0.001, Figure 2). The model of "LGE granularity" combining all independently significative LGE features showed the best improvement in model discrimination and reclassification above traditional prognosticators (C-statistic improvement: 0.90; NRI=41.9%; IDI=13.2%, Chi-2 global=450, all p<0.001; LR-test p<0.001, Figure 2). Conclusion In a large cohort of HCM patients, the "LGE granularity" model combining the extent, location, and pattern of LGE had an incremental prognostic value over and above traditional prognosticators to predict all-cause death.Prognostic value of LGE granularityIncremental prognostic value LGE granula

Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study

Abstract Background and Aims The recent Emmy trial underscored notable improvements in cardiac structure and function among post-acute myocardial infarction (AMI) patients treated with Empagliflozin, compared to those receiving a placebo. However, limitations such as a small sample size and a short follow-up period hindered the assessment of potential differences in actual clinical events between the groups. Consequently, our study aimed to evaluate the long-term outcomes, survival rates, rates of major adverse cardiovascular events (MACE), and heart failure (HF) incidence in patients with preserved ejection fraction (EF) who experienced AMI and underwent successful percutaneous coronary intervention (PCI), comparing those who received early initiation of Dapagliflozin with those who did not. Methods Data from the Taipei Medical University Research Database in Taiwan identified 7,081 inpatients who met the criteria of AMI status post successful PCI, with a left ventricular ejection fraction (LVEF) greater than 50% and absence of clinical symptoms indicative of heart failure. Exclusion criteria included individuals with a pre-existing diagnosis of heart failure before the index AMI episode and those with an LVEF below 50%, resulting in the exclusion of 357 patients from our study. The study subjects were then divided into two groups: those treated with Dapagliflozin and those not treated with Dapagliflozin, with matching for age, diabetes mellitus, and chronic kidney disease in a 1:2 ratio. Results The cohort study included of 756 patients who met the criteria of this study, among whom 252 were Dapagliflozin users and 504 were not. Over a 7-year follow-up period, Kaplan-Meier survival analyses revealed a significant reduction in cardiovascular mortality and all-cause mortality among Dapagliflozin users compared to non-users (p < 0.01). However, no significant differences were observed in heart failure, recurrent AMI, or stroke during the follow-up. Multivariate Cox analysis indicated the use of Dapagliflozin (hazard ratio = 0.310, 95% confidence interval = 0.188-0.510, p < 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p < 0.001) were both independent predictors of all cause death. Conclusions In patients with stabilized AMI, the use of Dapagliflozin was associated with a decreased risk of all-cause death, especially cardiovascular mortality. However, there were no significant differences observed in the rates of heart failure, recurrent AMI, or stroke over the seven-year follow-up period.Baseline characteristicsKaplan–Meier curves of all cause death

Combination of moderate-intensity statins and ezetimibe versus high-intensity statins alone for primary prevention of cardiovascular events

Abstract Background Combination of a moderate-intensity statin with ezetimibe can lead to similar reductions in cardiovascular events as monotherapy with a high-intensity statin in patients with established atherosclerotic cardiovascular disease (ASCVD). The comparative effectiveness of these two cholesterol-lowering strategies in the primary prevention setting is unknown. Purpose To compare incident ASCVD events associated with a combination of moderate-intensity statin and ezetimibe versus monotherapy with a high-intensity statin in adults without prior history of cardiovascular disease. Methods We conducted a new-user active comparator retrospective population-based cohort study in Canada. We included all adults aged ≥ 67 years (eligible for drug coverage) with a first prescription of either a combination of moderate-intensity statin with ezetimibe ("combination therapy") or high-intensity statin alone between January 2010 and December 2022. Patients were excluded if they had not received any prior lipid lowering therapies or had a history of myocardial infarction (MI), stroke, heart failure, peripheral vascular disease or prior coronary revascularisation at any time before or within 3 months of treatment initiation. The primary outcome was a composite of all-cause death, hospitalization for MI or stroke, or coronary revascularization. An inverse probability of treatment weighting propensity score was used to account for confounding (demographics, comorbidities, laboratory tests, other medications). Results Among 67,884 patients (mean age: 74.0±5.5y; 53% females), 8,798 (13%) initiated combination therapy and 59,086 (87%) initiated a high-intensity statin. At 1 year, after weighting, the mean achieved LDL-C was ~1.9 mmol/L in both groups. The median follow-up was 6.5 years. The cumulative incidence of the primary outcome at 10 years in the weighted cohort was 32.7% in the combination therapy group and 36.1% in the high-intensity statin group (HR: 0.87; 95% CI: 0.82 to 0.92; p<0.001; absolute risk reduction: 3.5%; 95% CI: 0.8 to 6.1; Figure 1). This result was primarily driven by a lower risk of all-cause death (HR: 0.85; 95% CI: 0.80 to 0.91; p<0.001; Figure 2) and stroke (cause-specific [cs] HR: 0.86; 95% CI 0.74 to 0.99; p=0.04), whereas no differences were observed in the risk of MI (csHR: 0.97; 95% CI: 0.82 to 1.15) or coronary revascularization (csHR: 0.97; 95% CI 0.85 to 1.11). Conclusion The combination of moderate-intensity statins with ezetimibe was associated with a lower risk of incident ASCVD compared with high-intensity statins alone among primary prevention patients in a real-world setting. These results were driven by a lower risk of all-cause death and stroke, but not coronary events. The influence of statin intolerance on the allocated strategy and adherence to therapy cannot be addressed in this analysis, which, along with verifying these estimates, may be best determined in a prospective randomized trial.

Adherence to the ABC pathway improves prognosis in patients with AF: preliminary findings from an updated meta-analysis of 360,000 patients

Abstract Background With the increasing complexity of patients with Atrial Fibrillation (AF), the ‘Atrial Fibrillation Better Care’ (ABC) pathway was proposed to streamline a holistic approach for the comprehensive management of patients with AF. The ABC pathway is based on three main pillars: ‘A’ Avoid stroke (through optimal anticoagulant use); ‘B’ Better symptom control; and ‘C’ Cardiovascular and Comorbidity management optimization. Such a holistic and integrated approach is currently recommended by international guidelines, including the ones from the European Society of Cardiology (ESC); a previous meta-analysis showed sub-optimal adherence to such approach in real-world cohorts, with an overall reduction in the risk of major outcomes in patients treated according to the ABC pathway. We hereby performed an updated systematic review and meta-analysis of the current evidence on the implementation of the ABC pathway in patients with AF. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. MEDLINE and EMBASE were searched for all studies reporting data on the prevalence of ABC pathway adherent management in patients with AF, and/or the association between ABC pathway management and the incidence of major outcomes, including all-cause death, cardiovascular death, thromboembolism, and major bleeding. Data on the prevalence of ABC pathway management were pooled using a generalized linear mixed model; number of events and total number of patients were pooled using a random-effect model. Pooled estimates were reported as odds ratios (OR) and 95% Confidence Intervals (95%CI); heterogeneity was estimated using the restricted maximum-likelihood estimator, and the Inconsistency index (I2) was also reported. Results 4,059 articles were retrieved from the literature search; after duplicates removal, title and abstract screening and full-text evaluation, 16 studies were included, for a total of more than 360,000 patients. Pooled prevalence of adherence to the ABC pathway was 28.5% (95%CI: 21.1-37.3%, I2=100%; Figure 1). Adherence to the ABC pathway was associated with a significant lower risk of all-cause death (pooled OR: 0.47, 95%CI: 0.40-0.56, I2=97%), cardiovascular death (pooled OR: 0.43, 95%CI: 0.33-0.56, I2=95%) and stroke (pooled OR: 0.61, 95%CI: 0.47-0.79, I2=91%; Figure 1). Patients treated adherent to the ABC pathway also showed a lower risk of major bleeding (pooled OR: 0.77, 95%CI: 0.66-0.90, I2=85%). Conclusions In this updated systematic review and meta-analysis, adherence to the ABC pathway was found in less than one-third of patients with AF. Implementation of the ABC pathway was associated with lower risk of all major adverse events in patients with AF, including all-cause death, and thromboembolic and bleeding events. These data further reinforce the need for routine implementation of the ABC pathway for the management of AF in clinical practice.Figure 1

Cardiovascular events and consequent risk of death in hematopoietic stem cell transplant recipients

Abstract Background Hematopoietic stem cell transplant (HSCT) represents a potentially curative approach for various hematologic cancers and bone marrow disorders. Advancements in safety and efficacy have broadened the application of HSCT to older individuals and those with concurrent medical conditions predisposing them to cardiovascular (CV) issues. Despite the significant survival benefits offered by HSCT, it is accompanied by both short- and long-term complications, leading to considerable morbidity and mortality. CV complications, including heart failure, arrhythmias, acute thrombosis, pulmonary hypertension, and pericardial effusions, are among the potential adverse events following HSCT. Aim for the present registry is to determine how much CV complications are related to short-term survival in patients after HSCT. Methods Observational, monocentric cohort study consecutively enrolling all patients undergoing HSCT from 2019 to 2023. Inclusion criteria was >18 years, autologous or allogeneic HSCT, and written informed consent for the participation in the study. All patients underwent a complete cardiological examination, including 12-lead ECG, echocardiography, and cardiac biomarkers, before HSCT, and after 2,6 and 12-months. CV-related adverse events were defined as systolic dysfunction (even asymptomatic), thromboembolism (both VTE and PE), stroke, arrhythmias, pericarditis and hypertensive crises. Results 91 patients (34% female; mean age 54 +/- 12 years) were followed-up for a median of 2 years after HSCT. Major risk factors' prevalence was overall low (hypertension 28%, dyslipidaemia 33%, diabetes 9%, and only 11 patients (12%) had a positive history for CV events (6 atrial fibrillation, 4 coronary heart disease, 1 stroke) before HSCT. During follow-up, 26 patients (29%) experienced at least one CV-related adverse event, of which 7 (8%) were serious enough to require an hospital admission. CV adverse events included 5 new heart failure diagnosis, 5 new atrial fibrillation diagnosis, 10 episodes of VTE/PE, 4 pericarditis, one stroke and one hypertensive crisis. Twenty of all CV-related adverse events were reported within the first six months after HSCT (77%). Having a CV-related AE within the first six months after HSCT is associated with an increased risk of all-cause death (39% vs. 17%; log-rank p=.01; Figure 1). Conclusions CV-related adverse events are common in patients undergoing HSCT and strikes an overall young and healthy population. Having a CV-related adverse event in the six months following HSCT is a heavy prognostic factor for all-cause mortality. Therefore, an optimal prevention strategy including arrhythmia monitoring, echocardiographic follow-up and guideline-driven thromboembolic prophilaxis could improve patients' survival after HSCT.Figure 1

Anthropometric measures and long-term mortality in heart failure with reduced ejection: debunking the obesity paradox

Abstract Background In patients with heart failure (HF), an "obesity-survival paradox" has been reported. Although body mass index (BMI) is the most commonly used anthropometric measure to assess adiposity, alternative indices such as the waist-to-height ratio may better reflect the location and amount of ectopic fat as well as the weight of the skeleton. Purpose To examine and compare the prognostic value of several alternative anthropometric measures with that of BMI in patients with non-ischemic HF with reduced ejection fraction (HFrEF) enrolled in the DANISH trial. Patients were eligible if they had non-ischemic HFEF, a left ventricular ejection fraction of <35%, New York Heart Association functional class II-III (IV if cardiac resynchronization therapy was planned), and elevated natriuretic peptides. The outcomes of interest were all-cause mortality and cardiovascular death. The association between anthropometric measures and all-cause death was examined with Cox regression models, adjusted for prognostic variables, including natriuretic peptides. Results Among 1,116 patients with non-ischemic HFrEF, there was no evidence for a BMI-related "obesity-survival paradox" during a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years). Indeed, compared to patients with a BMI 18.5-24.9 kg/m2 (N=363), those with a BMI >35 kg/m2 (N=91) had a significantly higher risk of all-cause death (HR 1.78 [95% CI 1.28-2.48]). Greater waist-to-height ratio (as an exemplar of indices not incorporating weight) was also associated with a higher risk of all-cause death, with a HR of 2.11 (95% CI, 1.53-2.92) for the highest quintile (N=205) compared with the lowest quintile (N=196). In the minimally adjusted restricted cubic spline models, the association between adiposity and all-cause death was more apparent for waist-to-height ratio than for BMI. A similar pattern was seen for cardiovascular death (Figure). Conclusion In patients with HFrEF, there was no evidence for an "obesity-survival paradox". Indeed, there was a clear association between adiposity and higher long-term mortality, which appeared to be stronger for waist-to-height ratio than for BMI. There is a need to test the potential benefits of intentional weight loss in patients with HFrEF and obesity.

The condition of myocardium reserves score from a cloud-based analytics platform of Holter ECG data indicates better cardiometabolic function in heart failure

Abstract Introduction Cardiometabolic dysregulation, particularly type 2 diabetes mellitus (T2DM), is associated with subtle myocardial pathologies, even in individuals without known cardiovascular disease. These subclinical changes, often undetectable by standard electrocardiogram (ECG) analytics, can offer valuable insights into the relationship between metabolic health and cardiac function. Novel ECG markers, developed through machine learning and artificial intelligence (AI), may provide the sensitivity needed to detect such changes. Aim This study aims to evaluate novel composite cardiac parameters from an analytics platform in the context of heart failure (HF), seeking to understand their relationship to cardiometabolic dysregulation. Methods Data from the MyoVasc study, a prospective cohort on HF, were analysed. Participants underwent extensive clinical phenotyping, including a Holter ECG assessment. Holter ECG data was processed based on machine learning and AI models on a cloud-based analytics platform (Cardiolyse, Helsinki, Finland), generating both traditional and proprietary ECG, and heart rate variability cardiac health markers. LASSO-penalized logistic regression adjusted for sex and age was performed to select the marker most strongly associated with T2DM. The identified marker was then evaluated in relation to cardiac function and structure as well as HF-related outcome. Results A total of 953 subjects (mean±SD age 64.6±10.5 years; 35.7% women) were included in the analyses. Symptomatic HF stage C/D was present in 54.8% (n=522) of subjects and diabetes mellitus in 22.4% (n=213). The Condition of Myocardium Reserves Score (CMRS) was the novel composite cardiac parameter selected based on its relationship with T2DM. In a Poisson regression model with robust variance adjusted for sex and age, a lower score was associated with T2DM (Prevalence ratio per SD 1.24, 95% confidence interval [1.14;1.36], P=0.0002). In multivariable linear regressions adjusted for traditional cardiovascular risk factors, comorbidities, and medication, a higher CMRS was associated with better global longitudinal strain (β per SD –0.82 [–1.11;–0.53], P<0.0001), diastolic function (left ventricular E/e’; β per SD –0.04 [–0.06;–0.01], P=0.0059) and systolic function (LV ejection fraction; β per SD 2.06 [1.46;2.67], P<0.0001). A lower CMRS independently predicted all-cause death (Hazard ratio per SD 1.25 [1.09;1.45], P=0.0020) and worsening of HF (HR per SD 1.44 [1.21;1.72], P<0.0001) in Cox regression analysis adjusted for the same confounders. Conclusion The Condition of Myocardium Reserves Score exhibited a strong association with cardiometabolic dysregulation. A higher CMRS indicated preserved cardiac function, while a lower score independently predicted increased risk of all-cause death and worsening HF. This novel score offers potential as a non-invasive tool for assessing cardiometabolic health and stratifying risk in patients with HF.

Predictors of discordance in estimating the presence of chronic kidney disease among patients with atrial fibrillation and impact on prescription of anticoagulants and cardiovascular outcomes

Abstract Background In patients with atrial fibrillation (AF), the prevalence, predictors and clinical implications of a potential discordance in estimating the presence/absence of chronic kidney disease (CKD) according to Cockroft-Gault (CG) and CKD-EPI formulas remain unclear. Objective To examine patients characterized by discordance in evaluation of renal function, specifically with regard to the threshold for defining the presence of CKD according to an estimated glomerular filtration rate (eGFR) < 60 ml/min, in a large cohort of European AF patients, and to assess the association with prescriptions of oral anticoagulants (OAC) and the risks of adverse outcomes. Methods Data related to AF patients enrolled in a large European observational prospective registry with an average follow up of 645.2 days were analysed. We evaluated renal function for assessing the presence of CKD according to CG and CKD-EPI formulas and we categorized the population in four groups: eGFR ≥ 60 ml/min according both to CG and CKD-EPI (Concordant ≥ 60); < 60 ml/min according to both formulas (Concordant <60); CG <60 ml/min and CKD-EPI ≥60 ml/min (Discordant-CKD-EPI), CG ≥ 60 ml/min and CKD-EPI <60 ml/min (Discordant-CG). Logistic regression analyses were used to assess factors associated with a Discordant assessment of CKD and its association with OAC therapy. Cox regression analysis was used to determine association between categories and the risk of adverse outcome. The primary endpoint was a composite of all-cause death and major adverse cardiovascular events (MACEs). Results 8.786 patients with AF (mean age 68.70, SD 11.58 years; 40.9% female) were included in the analysis. 1360 (15.5%) of them had Discordant CKD assessment: 577 (6.6%) with Discordant-CKD-EPI and 783 (8.9%) with Discordant-CG. Increasing age, female sex and coronary artery disease (CAD) were associated with Discordant-CKD-EPI, while BMI and heart failure (HF) showed an inverse association (Figure 1). Conversely, BMI and HF were factors significantly associated with Discordant-CG. Discordant-CKD-EPI patients showed lower odds of being prescribed with OAC therapy (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.54-0.95) with no significant differences regarding the type of OAC therapy (warfarin or direct oral anticoagulants). At Cox regression analysis, patients with Discordant-CKD-EPI showed a higher risk of composite endpoint events (Figure 2) and both Discordant-CKD-EPI and Discordant-CG patients were associated with a higher risk of all-cause death. Conclusions Age, BMI, female sex and comorbidities associated with AF (CAD and HF) significantly influenced the probability of having a discordant assessment of the presence of CKD, according to estimation of renal function impairment using CG or CKD-EPI formulas, respectively. A discordant assessment of CKD influenced the probability of being prescribed with OAC and was associated with a higher risk of adverse outcomes.Figure 1Figure2

Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes.

Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients. The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease. All-cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis. The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of therenal event (HR 5.15, 95% CI 2.51-10.6) and all-cause death (HR 2.30, 95% CI 1.20-4.42). A significant association was not observed between GNRI levels and cardiovascular events. We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes.

Renin–angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study

ABSTRACT Background While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial. Methods Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences. Results Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82, p < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48–0.83, p = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results. Conclusions Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death.

Kidney and cardiovascular outcomes in older population with mildly to moderately decreased kidney function - A nationwide cohort study.

Although the prevalence of chronic kidney disease (CKD) is increasing in the aging population, the clinical relevance of the CKD definition (glomerular filtration rate [GFR] &lt; 60 ml/min/1.73 m2) in older populations remains debatable. We investigated the clinical outcomes in older populations with mildly to moderately decreased GFR (45-59 ml/min/1.73 m2, CKD stage 3A). A total of 7,789,242 participants aged ≥ 40 years with estimated GFR (eGFR) ≥ 45 ml/min/1.73 m2 in national health screening examination from 2012 to 2017 were included in this retrospective cohort study using the Korean National Health Insurance Service database. The main outcomes included kidney failure, cardiovascular disease (CVD), and all-cause death. Cox regression hazard models were used to estimate the hazard ratios. The proportion of participants with eGFR 45-59 ml/min/1.73 m2 was 10.0% and 16.3% in the old (65-74 years) and very old (75 ≥ years) groups, respectively. Mildly to moderately decreased eGFR was associated with a higher risk of kidney failure, CVD, and all-cause death compared with eGFR 60-89 ml/min/1.73 m2 in the old and very old groups, regardless of proteinuria (adjusted hazard ratio [95% confidence interval] in the very old group without proteinuria: kidney failure 3.048 [2.495-3.722], CVD 1.103 [1.066-1.142], and all-cause death 1.172 [1.144-1.201]). Mildly to moderately decreased eGFR was associated with an increased risk of kidney failure, CVD, and all-cause death in the older population, regardless of proteinuria, suggesting the importance of appropriate monitoring and management in this population.

Elevated levels of PDGF-BB and VEGF are associated with a decreased risk of readmission or death in children with severe malarial anemia.

Children with severe malarial anemia (SMA) typically have low in-hospital mortality but have a high risk of post-discharge readmission or death. We hypothesized that the dysregulation of hematopoiesis, vascular growth factors, and endothelial function that occurs in SMA might affect risk of readmission or death. Plasma was obtained from children 18 months to 12 years old with SMA (N=145) in Kampala, Uganda on admission, and outcomes were assessed over 12-month follow-up. Admission plasma levels of ten biomarkers of vascular growth, hematopoiesis, and endothelial function were compared to risk of readmission or death over 12-month follow-up. Over 12-month follow-up, 19 of 145 children with SMA were either readmitted or died: 15 children were readmitted (13 with malaria) and 4 children died. In multivariable analyses adjusted for age and sex, elevated plasma levels of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) on admission were independently associated with a decreased risk of all-cause readmission or death (adjusted hazard ratios [95% confidence intervals], 0.28 [0.16-0.51] and 0.19 [0.08-0.48], respectively) and a decreased risk of readmission due to severe malaria (0.27 [0.15, 0.51] and 0.16 [0.05, 0.47]) but not with risk of uncomplicated malaria (1.01 [0.53, 1.95] and 2.07 [0.93-4.64]). In children with severe malarial anemia, elevated plasma levels of PDGF-BB and VEGF, two factors that promote angiogenesis, are associated with a decreased risk of readmission or death in the year following admission, primarily driven by a decrease in the risk of recurrent severe malaria.

Robotic right colectomy versus laparoscopic right colectomy in patients with right colon cancer: a comparative study

BackgroundThe study aimed to compare the clinical outcomes of robotic right colectomy (RRC) versus laparoscopic right colectomy (LRC) in patients diagnosed with right colon cancer, given the increasing adoption of robotic surgical techniques and their potential benefits in oncologic surgery.MethodsThis retrospective comparative study included patients who underwent right colectomy at Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, between January 2019 and May 2022. The primary outcomes measured were the number of lymph nodes harvested. Key secondary outcomes included the operation time, intraoperative blood loss, postoperative complications, hospitalization costs, overall survival (OS), and disease-free survival (DFS). Data were analyzed using multivariable Cox proportional hazards regression to adjust for potential confounders.ResultsA total of 225 patients (aged 65.23 ± 11.45, 108 males) with right colon cancer were included, with 100 (44.4%) patients underwent RRC. Patients who underwent RRC had significantly more lymph nodes harvested (27.69 ± 12.59 vs. 24.43 ± 9.42, P = 0.028), and incurred higher total hospitalization costs compared to those with LRC (9.68 ± 7.12 vs. 5.28 ± 1.23 ten-thousand-yuan, P < 0.001). The OS and DFS were comparable between RRC and LRC (both P > 0.05) within a median follow-up of 27 (range, 9–44) months. Multivariable cox proportional hazards regression showed that patients underwent RRC had significantly higher risk for all-cause death compared with those underwent LRC [hazards ratio (HR) = 2.303, 95% confidence intervals (CI): 1.625–3.265, P < 0.001].ConclusionPatients underwent RRC seemed to have significantly more numbers of lymph nodes harvested and higher risk for all-cause death and higher hospitalization costs compared with those underwent LRC. These findings suggest a need for careful consideration of the benefits and risks associated with robotic versus laparoscopic right colectomy in clinical practice.Trial registrationNot applicable.

Clinical relevance of protein-truncating variants of germline DNA repair genes in prostate cancer

BackgroundInterpreting genetic variants remains a challenge in prostate cancer (PCa). Although many annotation tools are available for prioritizing causal variants, the clinical relevance of these variants is rarely studied.MethodsWe collected a cohort study that included 274 PCa patients from June 2017 to December 2020 and sequenced 19 DNA damage repair (DDR) genes in these patients and explored the clinical consequence of these different approaches. We also examined all-cause and PCa-specific survival in DDR gene mutation carriers compared to non-carriers after androgen receptor (AR)-directed therapy.ResultsWe identified 13 variants from 19 DDR genes in a total of 14 (5.1%) patients who had at least one presumed pathogenic mutation using different annotation methods. Four variants were annotated as pathogenic, 11 variants were predicted as protein-truncating variants (PTVs), four variants received proxy-deleterious (Combined Annotation-Dependent Depletion scores of > 30), and only one variant was identified as a pathogenic variant or as having a functional effect by all three methods. PCa patients with PTVs were significantly associated with early onset, high cancer stage, and a worse response to AR-directed treatment. However, patients carrying a proxy-deleterious variant were only associated with a higher T (tumor) stage and N (node) stage than those without such a variant, but not associated with other clinical characteristics. In patients treated with AR-directed therapy, patients with a PTV showed an increased risk of all-cause death (adjusted hazard ratio (aHR) = 3.51, 95% confidence interval (CI): 1.06 ~ 11.56) and PCa-specific death (aHR = 4.49, 95% CI: 1.87 ~ 10.77) compared to non-PTV carriers after adjustment. We were unable to examine gene-specific risks due to the small number of patients.ConclusionsPTVs may assist in guiding treatment and early screening in PCa, while population-specific data for pathogenic variants are still being amassed.

Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study

BackgroundA Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes.MethodsThe Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006–2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%).ResultsWith the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min− 1·1.73 m− 2. The median difference was 4.10 ml·min− 1·1.73 m− 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations.ConclusionChanging from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min− 1·1.73 m− 2, but virtually no impact on mortality prediction.Trial registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.

A systematic review and meta-analysis of frailty in patients with heart failure.

To systematically evaluate the effect of frailty on the prognosis of patients with heart failure. Computer searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang Data Knowledge Service platform, Weipu full-text database of Chinese scientific and technological journals, and Chinese biomedical literature database from August 12, 2022. After literature screening was completed by two researchers, the data extraction (such as study type, sample size, age of included patients, New York Heart Association (NYHA) Functional Classification, frailty assessment tool, frailty positive rate, outcome indicators, etc.) was performed and the risk of bias in the included studies was assessed. Meta-analysis was performed using Revman 5.4 and Stata 14.0 software. A total of 32 studies were included, including 406,269 patients with heart failure. All included studies were rated high overall quality. The results of meta-analysis showed: Frailty increases the risk of all-cause death in patients with heart failure (hazard ratio [HR] = 1.73, 95% confidence interval [CI]: 1.50 - 2.00, p < 0.001), unplanned readmission (HR = 1.96, 95% CI: 1.21 - 3.17, p = 0.006), and joint endpoint risk (HR = 1.66, 95% CI: 1.48 - 1.86, p < 0.001). Current evidence suggests that frailty increases the risk of all-cause death, unplanned readmission, and joint endpoints in patients with heart failure.

Frailty, age, and treatment effect of surgical coronary revascularization in ischemic cardiomyopathy: a post hoc analysis of the STICHES trial.

Frailty is common among older patients with heart failure (HF). The efficacy of coronary artery bypass grafting (CABG) on the risk of mortality amongfrailpatients with ischemic cardiomyopathy and HF is uncertain, and whether frailty burden modifies the treatment benefits of CABG among these patients is unknown. We performed a post hoc analysis of the STICHES trial, a randomized trial of CABG with medical therapy vs medical therapy alone among participants with ischemic cardiomyopathy with ejection fraction ≤ 35%. Baseline frailty was assessed through a Rockwood Frailty Index (FI), and based on FI cut-offs from prior HF studies, participants with FI ≥ 0.311 were classified as more frail, and those with FI < 0.311 were classified as less frail. A multivariable Cox proportional hazard model with multiplicative interaction terms was constructed to evaluate whether frailty status modified the treatment effect of CABG on mortalityin the overall trial cohort and among those < 60 vs ≥ 60 years of age. Of 1187 participants (12.4% female, 2.6% Black, median FI = 0.33 [IQR 0.27-0.39]), 678 were characterized as more frail. Frailty burden did not modify the efficacy of CABG on the risk of all-cause death in the overall cohort (Pint CABG × frailty = 0.2). In age stratified analysis,Baseline frailty status did not modify the treatment effect of CABG on the risk of all-cause mortality among younger (< 60years, Pint CABG × frailty = 0.2) as well as older participants (≥60years, Pint CABG × frailty = 0.6). In this post hoc analysis of the STICHES trial, baseline frailty status did not modify the efficacy of CABG in the overall cohort as well asamong younger or older participants. Frailty alone should not be used as a criterion to determine the utilization of CABG among patients with ischemic cardiomyopathy.

Dose-Response Independent and Joint Associations of Physical Activity and Sedentary Behavior With Mortality Risk in 40 156 Australian Adults With Coronary Heart Disease.

Little is known about the relationship between physical activity (PA) and sedentary behavior (SB) with death in people with coronary heart disease. The aim was to examine the independent and joint associations of PA and SB with death. This is a prospective cohort study including Australian participants aged ≥45 years with self-reported coronary heart disease (2006-2020). Self-reported PA (min/wk) and SB (h/d) were the exposures. Cardiac and all-cause death were the main outcomes. The cohort included 40 156 participants (mean age, 70.3 (SD, 10.3) years; 15 278 women [38%]). During a median follow-up of 11.1 (interquartile range, 6.2-14.4) years, 2497 cardiac and 12 240 all-cause deaths were recorded. Compared with no PA, a 20% to 30% lower risk of cardiac and all-cause death was associated with any level of PA. Walking and moderate to vigorous PA at 150 to 300 min/wk was associated with a 43% to 44% lower risk of cardiac death and 35% to 40% lower risk of all-cause death. Compared with ≥10.5 h/d of SB, participants who were sedentary for 7 to 10.4 h/d experienced an ≈25% reduced associated risk of cardiac and all-cause death. A 56% associated reduction in all-cause mortality risk was found if SB was limited to <3.4 h/d. If participants completed >150 min/wk moderate to vigorous PA and spent <7 h/d in SB, the associated risk of cardiac and all-cause death was reduced by ≈70%. All people with coronary heart disease should be encouraged to meet the PA guidelines and limit SB to <7 h/d, noting any increase in physical activity and decrease in SB is better than none to prevent premature death.

Association of depressive symptoms and engagement in physical activity with event-free survival in patients with heart failure

BackgroundHeart failure (HF) subtype, depressive symptoms, and physical inactivity independently contribute to survival outcomes, but the effect of the interaction of these variables on survival outcomes remains unknown. ObjectivesWe aimed to determine whether depressive symptoms and engagement in physical activity differentially interact to predict the combined endpoint of all-cause death or rehospitalization among patients with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF). MethodsThis study was a secondary analysis. The sample was categorized by the presence or absence of depressive symptoms, and engagement or non-engagement in physical activity. Cox proportional hazard modeling was used to predict the combined endpoint of all-cause death or rehospitalization. ResultsA total of 1002 patients with HF were included (mean age 64.3 ± 12.7 years; 637 males [64 %]; 844 White [84 %]). Among them, 35.3 % did not engage in physical activity, while 64.7 % engaged in any level of physical activity, and 29.7 % had depressive symptoms. In both subtypes, depressive symptoms were associated with the highest risk of all-cause death or rehospitalization. Among patients with HFrEF, those with depressive symptoms who did not engage in physical activity were associated with a 136 % higher risk of the combined endpoint, while among those with HFpEF, depressive symptoms and engagement in physical activity were associated with a 78 % higher risk. ConclusionsDepressive symptoms and lack of physical activity predicted the combined endpoint of all-cause death or rehospitalization among patients with HFrEF, while depressive symptoms alone were the strongest predictor among patients with HFpEF.

Systemic immune inflammation index with all-cause and cause-specific mortality: a meta-analysis.

Studies have reported an association among systemic immune inflammation index (SII), all-cause and cause-specific mortality, but the results are inconsistent. To comprehensively explore the association between Systemic Immune Inflammation (SII) and the risk of all-cause mortality, cardiovascular disease (CVD), and cancer mortality. A meta-analysis was conducted by reviewing existing literature. The search encompassed prominent databases including PubMed, Embase, Cochrane, and the Web of Science, with the cutoff date set at March 1, 2024. Furthermore, subgroup analyses and dose-response assessments were undertaken to provide a nuanced exploration of mortality risk factors. A total of 33 articles were included (427,819 participants). In the study, SII was associated with an increased risk of all-cause mortality (HR = 1.45, 95%CI [1.36,1.54], P < 0.05). SII increased the risk of CVD mortality (HR = 1.44, 95%CI [1.29,1.60], P < 0.05). The Linear independence shows that for every 100 units increase in SII, the risk of all-cause and CVD death increases by 5% and 6%. SII was not associated with a statistically significant risk of cancer death (HR = 1.09, 95%CI [0.96,1.23], P < 0.05). Meta-analysis showed that SII was associated with all-cause mortality and CVD mortality. More data and basic research are needed to confirm the association.