Clinical Cardiovascular Outcomes Research Articles

Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials

GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials. For this meta-analysis, we searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials that included at least 500 participants with type 2 diabetes, compared a GLP-1 receptor agonist with placebo with at least 12 months of follow-up, and reported a primary clinical kidney or cardiovascular outcome, from database inception to March 26, 2024. Post hoc, we included the SELECT trial (NCT03574597), which enrolled participants with cardiovascular disease and a BMI of 27 kg/m2 or more without diabetes. Study-level summary data were extracted independently by two authors for inclusion in this random-effects analysis. The main kidney outcome was a composite outcome, consisting of kidney failure (kidney replacement therapy or a persistent estimated glomerular filtration rate [eGFR] <15 mL/min per 1·73 m2), a sustained reduction in eGFR by at least 50% or the nearest equivalent, or death from kidney failure. The main cardiovascular outcome was MACE, consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. This study is registered with PROSPERO, CRD42024528864. Of the 5140 records identified through the literature search, 11 trials, involving 85 373 participants (29 386 female, 55 987 male), were included in the meta-analysis. In participants with type 2 diabetes (67 769), GLP-1 receptor agonists reduced the composite kidney outcome by 18% compared with placebo (hazard ratio [HR] 0·82, 95% CI 0·73-0·93; I2 =26·41%), kidney failure by 16% (HR 0·84, 0·72-0·99; I2 =0%), MACE by 13% (HR 0·87, 0·81-0·93; I2 =49·75%), and all-cause death by 12% (HR 0·88, 0·83-0·93; I2 =0%). The effect on the composite kidney outcome (HR 0·81, 95% CI 0·72-0·92; I2 =23·11%), kidney failure (HR 0·84, 0·72-0·98; I2 =0%), MACE (HR 0·86, 0·80-0·92; I2 =48·9%), and all-cause death (HR 0·87, 0·82-0·91; I2 =0%) was similar when the SELECT trial was included, with no evidence of heterogeneity between this trial and those including participants with type 2 diabetes (pheterogeneity >0·05). There was no difference in the risk of serious adverse events, including acute pancreatitis and severe hypoglycaemia, between the GLP-1 receptor agonist and placebo groups (risk ratio [RR] 0·95, 95% CI 0·90-1·01; I2 =88·5%). However, treatment discontinuation due to adverse events occurred more frequently in the GLP-1 receptor agonist groups (RR 1·51, 95% CI 1·18-1·94; I2 =96·3%). We found evidence that GLP-1 receptor agonists significantly reduce clinically important kidney events, kidney failure, and cardiovascular events. None.

Definitions of clinical study outcome measures for cardiovascular diseases: the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart).

Standardized definitions for outcome measures in randomized clinical trials and observational studies are essential for robust and valid evaluation of medical products, interventions, care, and outcomes. The European Unified Registries for Heart Care Evaluation and Randomised Trials (EuroHeart) project of the European Society of Cardiology aimed to create international data standards for cardiovascular clinical study outcome measures. The EuroHeart methods for data standard development were used. From a Global Cardiovascular Outcomes Consortium of 82 experts, five Working Groups were formed to identify and define key outcome measures for: cardiovascular disease (generic outcomes), acute coronary syndrome and percutaneous coronary intervention (ACS/PCI), atrial fibrillation (AF), heart failure (HF) and transcatheter aortic valve implantation (TAVI). A systematic review of the literature informed a modified Delphi method to reach consensus on a final set of variables. For each variable, the Working Group provided a definition and categorized the variable as mandatory (Level 1) or optional (Level 2) based on its clinical importance and feasibility. Across the five domains, 24 Level 1 (generic: 5, ACS/PCI: 8, AF: 2; HF: 5, TAVI: 4) and 48 Level 2 (generic: 18, ACS-PCI: 7, AF: 6, HF: 2, TAVI: 15) outcome measures were defined. Internationally derived and endorsed definitions for outcome measures for a range of common cardiovascular diseases and interventions are presented. These may be used for data alignment to enable high-quality observational and randomized clinical research, audit, and quality improvement for patient benefit.

Cardiovascular Profile of Patients With COVID-19 Infection Admitted in a Tertiary Care Hospital in Manila, Philippines: A 2-Year Single-Center Retrospective Study

INTRODUCTION: Respiratory symptoms are the most commonly observed clinical manifestations in patients with COVID-19 infection; however, some patients may present with cardiovascular complications. Patients with underlying cardiovascular diseases are associated with increased mortality risk. This study aimed to provide local data on the clinical profile and cardiovascular outcomes and to determine predictors of in-hospital mortality among COVID-19 patients admitted to a tertiary care hospital in the Philippines. METHODS: This single-center retrospective study included hospitalized patients diagnosed with COVID-19 between March 2020 and May 2022. Clinical parameters were subjected to univariate and multivariate regression analyses, with in-hospital mortality as the dependent variable. RESULTS: A total of 1341 patients were admitted with a mean age of 50 years, half of whom were males. Hypertension is the most common comorbidity (728 [54.3%]), followed by diabetes mellitus (393 [29.3%]) and heart disease (136 [10.1%]). Patients admitted to the intensive care unit had significantly higher systolic blood pressure than non–intensive care unit patients (127 ± 19 vs 139 ± 26 mm Hg; P &lt; 0.001), as well as higher plasma erythrocyte sedimentation rate, C-reactive protein, D-dimer, troponin, ferritin, and lactate dehydrogenase. The most common cardiac complications observed were heart failure (39%), acute cardiac injury (30%), and arrhythmia (30%). During hospitalization, 100 patients (7.4%) died; almost half were admitted to the critical care unit, and 84 had cardiac complications, with heart failure (21%) being the most common. Sinus tachycardia was the most common electrocardiographic abnormality (436 [32%]). Univariate analysis showed diabetes (odds ratio [OR], 2.7; P = 0.029) and hypertension (OR, 3.4; P = 0.11). Multivariate analysis revealed that age (OR, 1.095; P &lt; 0.05) and admission duration (OR, 0.906; P &lt; 0.05) were significantly associated with mortality. CONCLUSION: This study highlights the clinical characteristics of patients contracted with COVID-19 who may experience several cardiac conditions. Therefore, particular attention should be given to the role of preexisting cardiovascular diseases and cardiac complications that may contribute to long-term outcomes. KEYWORDS: cardiac complications, COVID-19, cardiovascular outcomes

Association of long-term visit-to-visit glycemic variability with risk of adverse clinical outcomes in diabetic patients with heart failure with preserved ejection fraction

Abstract Background Previous research has linked glycemic variability (GV) with cardiovascular issues in type 2 diabetes mellitus. However, its impact on patients with heart failure with preserved ejection fraction (HFpEF) remains understudied. Purpose In this study, we aim to examine how glycemic variability influences on clinical cardiovascular outcomes in diabetic HFpEF patients. Methods We conducted a retrospective cohort analysis utilizing the electronic medical records of a tertiary medical center in Taiwan between 2014 and 2019. Diabetic patients diagnosed with HFpEF were included in the study. The coefficient of variability of fasting glucose (FGCV) was determined for each individual, and the FGCVs were categorized into tertiles. We analyzed the association between FGCV and the risks of hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiac mortality, and overall mortality. Results A total of 74,835 patients were enrolled in this study. Among them, 753 diabetic patients with concomitant with HFpEF and measured FGCV were identified, with a median follow-up duration of 38.1 months. In the multivariable regression model, the third tertile of FGCV demonstrated a significant association with an elevated risk of HHF and overall mortality compared to the first tertile (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.03-1.50, p = 0.026; HR 1.64 [1.15-2.26], p = 0.006). Although a higher FGCV exhibited a trend towards increased AF and cardiac mortality, statistical significance was not reached (HR 1.19 [0.91-1.56], p=0.208; HR 1.64 [0.87-3.12], p=0.129). The Kaplan-Meier analyses revealed a significant association between higher FGCV and both HHF and overall mortality (log-rank p = 0.022 and &amp;lt;0.001, respectively). Conclusions Our study highlights a significant association between increased GV and a higher incidence of HHF as well as an overall mortality rate in diabetic individuals with HFpEF.

Clustering analysis based on clinically available data for improving risk stratification and outcome prediction of hypertension

Abstract Background Hypertension (HTN) is a heterogeneous condition with several factors contributing to adverse outcomes. Machine learning can harness complex data to unveil outcome predictors and guide prevention. Purpose To use clustering analysis on clinical data to identify HTN risk profiles and their associations with cardiovascular abnormalities and clinical outcomes. Methods A cohort of 14,840 UK Biobank hypertensive participants without pre-existing heart failure (HF) who underwent cardiovascular magnetic resonance (CMR) assessment was examined using K-means clustering on 79 clinical attributes. The clusters’ association with incident HF, mortality, atrial fibrillation (AF), and major adverse cardiovascular events (MACE) were evaluated, alongside imaging characteristics, with mediation analysis probing the role of imaging in risk differentiation. All post-hoc analyses were adjusted for vascular risk factors (VRFs), including diabetes, hypercholesterolaemia, previous myocardial infarction. Results Three distinct clusters differing considerably in lifestyle habits, cardiovascular risk factors, electrocardiographic parameters, and cardiometabolic profiles were identified. Cluster 1 (lowest risk), predominantly females, exhibited the most favourable metabolic profile and outcomes. Cluster 2 (highest risk), predominantly males, had the most adverse metabolic and cardiovascular profiles, and the highest risk of all adverse outcomes, especially AF and HF (hazard ratio (HR) 1.80 [1.45–2.25] and 1.85 [1.39–2.46]; p &amp;lt;0.005). This group was associated with more eccentric LV hypertrophy (LVH), overall poorer left atrial emptying function (LAEF), bi-ventricular systolic function and LV mechanics, and higher systemic vascular resistance (Figure 1). Cluster 3 (intermediate risk) was a more heterogeneous group with the highest burden of diabetes and adiposity and a moderate rise in AF and MACE risk (HR 1.61 [1.12-2.32] and 1.30 [1.07-1.58]; p &amp;lt;0.05). This cluster was associated with concentric LV remodelling and better indices of cardiac mechanics, but greater impairment in LA booster pump function (active LAEF) than Cluster 2 (Figure 1). Cluster 2's effect on MACE was mostly mediated through LV mass increase (proportion mediated, 67%), followed by changes (reducing) in LV global longitudinal strain (33%), and ejection fraction (25.4%). The indirect effect of CMR changes in the association between cluster 3 and MACE was much smaller with the highest proportion of the effects mediated through increased myocardial wall thickness (26%) but not LV mass, and changes in all the components of LA function. Conclusions Clinical data clustering provides insight into distinct HTN risk profiles, each with specific imaging characteristics and clinical trajectories, hinting at different pathophysiological mechanisms. Enhanced phenotyping can facilitate tailored interventions based on the disease subtype and improve clinical outcomes.Figure 1.

Impact of body mass index on aortic valve stenosis and its clinical outcomes in early adulthood: a long-term study of young men

Abstract Aims Studies investigating associations between body mass index (BMI), incidence of aortic valve stenosis (AVS), and clinical outcomes in AVS patients are scarce. Purpose To investigate the relationship between BMI in youth and subsequent diagnosis of AVS. A secondary aim was to determine the role of obesity in clinical outcomes in individuals diagnosed with AVS. Methods This was a nationwide, register-based cohort study of 1 701 390 men (mean age, 18.3 ±0.8 years) enrolled in compulsory conscription for military service in Sweden from 1969 through 2005. Anthropometrics, blood pressure, fitness, muscle strength and IQ were recorded at baseline. AVS cases and cardiovascular outcomes were identified according to the International Classification of Diseases (ICD)-10 registered in the National patient register and Cause of Death Register through the Swedish 12-digit personal identification number. BMI (kg/m2) was categorized as &amp;lt;18.5, 18.5–&amp;lt;20, 20–&amp;lt;22.5, 22.5–&amp;lt;25, 25–&amp;lt;27.5, 27.5 &amp;lt;30, 30–&amp;lt;35, and 35–&amp;lt;50 kg/m2. Cox proportional hazard models were used to estimate the association between adolescent BMI and future hospitalization for AVS while adjusting for potential confounders. The BMI reference was set as 20–&amp;lt;22.5. Those who developed AVS formed a subcohort that was followed until a first clinical cardiovascular outcome of death, cardiovascular mortality, Heart failure, Atrial fibrillation, myocardial infarction, or ischaemic stroke. Results During a median follow-up of 32 years (IQR, 24-41 years), 5766 cases (mean age 54.7±9.4 years) of AVS were diagnosed. After adjustment, underweight subjects with a BMI of &amp;lt;18.5 kg/m2, compared to those with a low-normal BMI (20.0–&amp;lt;22.5 kg/m2) showed lower risk (HR 0.70; 95% CI 0.61–0.80) of AVS. The multivariable-adjusted HR for AVS increased from HR 1.28; 95% CI 1.17–1.39 for BMI 22.5–&amp;lt;25 kg/m2 to HR 1.91; 95% CI 1.12–3.25 for those with BMI 35–50 kg/m2. Further on, individuals diagnosed with AVS were followed for a median of ~5.5 years. The multivariable-adjusted HR for all-cause mortality, cardiovascular mortality, and heart failure for obese (BMI 30–50 kg/m2), compared to BMI &amp;lt;20.0 kg/m2 in men diagnosed with AVS, were 4.69 (95% CI 2.61–8.44), 4.09 (95% CI 1.72–9.73), and 2.76 (95% CI, 1.36–5.60), respectively. Conclusions Elevated BMI in youth, even within the normal range, is associated with increased risk of developing AVS, while subnormal BMI was protective. Excess weight in youth diagnosed with AVS is associated with higher risk of subsequent clinical outcomes. These findings are novel, generating new questions as to potential mechanisms and implying more vigilant monitoring of patients with AVS and a history of obesity in youth.Figure 1Figure 2

Prediction of cardiovascular risk in patients type 2 diabetes using the SCORE2-Diabetes risk score

Abstract Background/Introduction The SCORE2-Diabetes risk score was developed to predict the risk of cardiovascular events (CV-death, non-fatal MI and non-fatal stroke) in patients with T2DM without known cardiovascular disease. Current ESC guidelines recommend the use of this risk score to tailor treatment strategies in this population. Purpose We sought to determine whether the SCORE2-Diabetes risk score was able to appropriately stratify an international cohort of patients from recent cardiovascular clinical outcomes trials. Furthermore, we sought to determine the accuracy and precision of the model including in patients with and without known cardiovascular disease. Methods Patients from 4 randomized cardiovascular outcome trials (DEVOTE, LEADER, PIONEER-6, SUSTAIN-6) were included (n=23,464). Mean follow-up was 2.6 years and outcomes were adjudicated. The SCORE2-Diabetes risk score was calculated using the uncalibrated version which does not account for risk-region. Patients were stratified into low (&amp;lt;5%), moderate (5-&amp;lt;10%), high (10-&amp;lt;20%), and very high risk (≥20%) groups. The SCORE2-Diabetes risk predication model was designed to predict 10-year risk; however, given the mean follow-up from the cohort, outcomes were reported at 36 months. The Brier score, which evaluates estimated risk, and c-index, which evaluates the ability to discriminate between participants, were used to evaluate the precision of the risk score. We further compared the risk score with an estimated risk of MACE calculated using a cause specific Cox model that accounts for competing risk. Results Most patients in the cohort did not have prior myocardial infarction or stroke (57.4%, n=13,467). The SCORE2-Diabetes risk score was able to stratify patients into low, moderate, high, and very high risk cohorts (Figure 1). Observed cardiovascular events at 36 months were higher than the SCORE2-Diabetes risk score predicted (Table 1). The risk score, when included in a regression model, independently predicted cardiovascular death, myocardial infarction, or stroke (HRadj 1.03, p&amp;lt;0.001) and non-cardiovascular death (HRadj 1.05, p&amp;lt;0.001). Including the score in models with only age and sex improved the discrimination and performance of the model. The c-index for the risk score in the overall cohort was 0.62 and was 0.66 in the cohort without known cardiovascular disease. When using the Brier score to evaluate the utility of the model, the Brier score of the SCORE2-D model was 0.08 which is no different than a null model which assumes a baseline risk of 10% in all patients. Conclusion In a cohort of patients that was older, more geographically diverse, and at higher risk of cardiovascular events, the SCORE2-D risk score appropriately stratified patients into categories of risk. However, the overall risk prediction underestimated the risk of cardiovascular events and the discrimination of the risk score was modest.Figure:CV events over timeTable:CV events by risk group

Remote monitoring and prioritisation for patients awaiting transcatheter aortic valve implantation safely mitigates longer waiting times

Abstract Background • The UK National Health Service (NHS) faces an unprecedented backlog of over 400,000 patients awaiting critical cardiac procedures, incurring thousands of excess deaths (1). • Longer waiting times to transcatheter aortic valve implantation (TAVI) can increase rates of unplanned hospitalisation and death (2). • Remote patient monitoring (RPM) can improve cardiovascular clinical outcomes (3), but its effectiveness in detecting and managing TAVI waiting list deterioration is untested. Purpose 1. Measure the systemic increase in waiting time to TAVI 2. Determine if RPM and prioritisation: · Is acceptable to patients · Detects clinical deterioration · Mitigates the expected increase in adverse events associated with longer waiting times · Does not unfairly disadvantage patients who are not prioritised Methods • We performed an observational cohort study including all patients awaiting TAVI at one UK regional centre between 24th April and 15th November 2023. • Patients were supported to complete an online or telephone-based weekly symptom questionnaire. • Responses were monitored by non-specialist nurses staffing a 'hub', with rule-based escalation to the TAVI team, who could prioritise treatment (Figure 1). • A historical control cohort who did not receive RPM was identified, as sequential unselected patients on the TAVI waiting list in reverse order, from 24th April 2023 to 1st January 2023. This cohort was propensity score-matched to adjust for age, sex, ethnicity and comorbidities. • Waiting time was defined as the date difference between a patient being placed on the waiting list and TAVI completion. • We defined patient acceptability as &amp;gt;80% engagement with at least one symptom questionnaire. • Sensitivity was calculated as the percentage of escalations to the TAVI Consultant resulting in prioritisation. • Kaplan-Meier survival analysis was performed for the primary endpoint of adverse events, defined as emergency department presentation, unplanned hospitalisation or death. Results • The median waiting time to TAVI increased by one month (104 days versus 75 days, p&amp;lt;0.001). • There was 99% (200/202) engagement with RPM • Despite the increased waiting time, there was no significant difference in rate of adverse events between the propensity score-matched RPM and historical control groups (12.5% versus 13.7%, p=0.86) (Figure 2) • 87% (27/31) of escalations to the TAVI Consultant resulted in treatment prioritisation • There was a non-significant difference in median waiting time between prioritised and non-prioritised patients during the study period, but with no clinical consequence to the delay (97 versus 120 days, p=0.16). Conclusions • An RPM pathway can detect patient deterioration on TAVI waiting lists with high sensitivity • RPM-based prioritisation for patients awaiting TAVI can mitigate the increased risk of adverse events associated with longer waiting times, without unfairly disadvantaging non-prioritised patients.Figure 1.RPM pathwayFigure 2

Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events, and Safety Outcomes in Patients With Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-Based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose cotransporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the United States, evaluating SGLT2i versus dipeptidyl peptidase-4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PSs) based on clinical and demographic factors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 95% CI 0.50-0.76), end-stage renal disease (HR 0.40, 95% CI 0.20-0.80), heart failure (HR 0.72, 95% CI 0.56-0.92), emergency department visits (HR 0.90, 0.82-0.99), and severe sepsis (HR 0.61, 95% CI 0.39-0.94). Risks of all-cause mortality (HR 0.89, 95% CI 0.65-1.21), lupus nephritis (HR 0.67, 95% CI 0.38-1.15), myocardial infarction (HR 0.81, 95% CI 0.54-1.23), stroke (HR 1.03, 95% CI 0.74-1.44), and hospitalizations (HR 0.76, 95% CI 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 95% CI 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 95% CI 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.07, 95% CI 0.53-2.14) and fractures (HR 0.95, 95% CI 0.66-1.36). In this emulated clinical trial, treatment with SGLT2i, compared to DPP4itherapy, was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Obesity and cardiovascular risk: a primer for the clinician.

Obesity is a significant risk factor for the development of cardiovascular diseases. This review addresses the complex interaction between obesity and cardiovascular risk, highlighting dysfunctional adiposity as a crucial precursor in the metabolic renal cardiovascular continuum. The underlying pathophysiological mechanisms are reviewed, emphasizing the importance of risk identification and proper stratification, as well as the various available treatment strategies, including pharmacological and non-pharmacological interventions that have proven to reduce cardiovascular risk. Practical tools and evidence-based strategies are provided to enhance clinical management and cardiovascular health outcomes in this particularly vulnerable patient population.

Cardiovascular effects and clinical outcomes in acute opioid toxicity: A case-control study from Port Said and Damietta Governorates Egypt

Substance abuse, particularly opioid intoxication, presents a significant public health challenge, leading to severe cardiovascular complications. This case-control study assessed the cardiac profile and clinical outcomes of 51 patients with confirmed acute opioid toxicity, compared to 51 control participants, in general hospitals across Port Said and Damietta governorates, Egypt. The study revealed that opioid-intoxicated patients exhibited significant cardiovascular abnormalities, including hypotension (39.2 %) and electrocardiogram (ECG) changes (72.5 %), with sinus bradycardia (51 %) being the most common. Additionally, echocardiographic abnormalities were found in 40 % of cases, with abnormal regional wall motion and valvular defects observed in several patients. Elevated levels of cardiac enzymes, such as Troponin-I and CK-MB, were significantly correlated with increased ICU stay length and higher mortality rates. The most common morbidities included coma (64.7 %) and shock (39.2 %). The study underscores the critical need for early cardiac assessment in opioid-intoxicated patients to predict clinical outcomes and guide therapeutic interventions.

Understanding the Role of Oxidative Stress in Platelet Alterations and Thrombosis Risk among Frail Older Adults.

Frailty and cardiovascular diseases are increasingly prevalent in aging populations, sharing common pathological mechanisms, such as oxidative stress. The evidence shows that these factors predispose frail individuals to cardiovascular diseases but also increase the risk of thrombosis. Considering this background, this review aims to explore advances regarding the relationship between oxidative stress, platelet alterations, and cardiovascular diseases in frailty, examining the role of reactive oxygen species overproduction in platelet activation and thrombosis. The current evidence shows a bidirectional relationship between frailty and cardiovascular diseases, emphasizing how frailty not only predisposes individuals to cardiovascular diseases but also accelerates disease progression through oxidative damage and increased platelet function. Thus, oxidative stress is the central axis in the increase in platelet activation and secretion and the inadequate response to acetylsalicylic acid observed in frail people by mitochondrial mechanisms. Also, key biomarkers of oxidative stress, such as isoprostanes and derivate reactive oxygen metabolites, can be optimal predictors of cardiovascular risk and potential targets for therapeutic intervention. The potential of antioxidant therapies in mitigating oxidative stress and improving cardiovascular clinical outcomes such as platelet function is promising in frailty, although further research is necessary to establish the efficacy of these therapies. Understanding these mechanisms could prove essential in improving the health and quality of life of an aging population faced with the dual burden of frailty and cardiovascular diseases.

Impaired Left Atrial Reserve Function in Heart Failure With Preserved Ejection Fraction.

Left atrial (LA) dysfunction is common in heart failure (HF) with preserved ejection fraction. However, data on the pathophysiologic impacts of impaired LA functional reserve remained limited. We sought to determine the association of abnormal LA dynamics during exercise with cardiovascular reserve, exercise capacity, and clinical outcomes. Patients with HF with preserved ejection fraction (n=231) and controls without HF (n=219) underwent exercise stress echocardiography with simultaneous expired gas analysis. LA function was assessed at rest and during exercise using speckle-tracking echocardiography. Patients with HF with preserved ejection fraction demonstrated less increase in LA reservoir and booster pump strain during exercise than those in controls. The degree of LA dilation was more closely related to exercise LA reservoir strain than to resting LA strain (Meng test, P=0.002). The presence of impaired LA reservoir strain during exercise was associated with poorer biventricular systolic reserve and cardiac output augmentation, more severe right ventricular-pulmonary artery uncoupling, and lower peak oxygen consumption. Patients with a lower exercise LA reservoir strain had a 2.7-fold increased risk of HF events (hazard ratio, 2.66 [95% CI, 1.32-5.38]; P=0.006). Among patients with follow-up echocardiography, initiation of guideline-directed medical therapy or atrial fibrillation ablation showed significant improvements in LA reservoir (P<0.001 and P=0.022) and booster pump strain (P=0.011 and 0.028) at rest and during exercise, respectively. Impaired LA reservoir function during exercise in HF with preserved ejection fraction is associated with biventricular reserve limitations, exercise intolerance, and increased risks of HF events.

Preclinical models of Glycaemic variability recapitulate Clinical Cardiovascular outcomes in Diabetes

Preclinical models of Glycaemic variability recapitulate Clinical Cardiovascular outcomes in Diabetes

Blood pressure response index and clinical outcomes in patients with septic shock: a multicenter cohort study

Sepsis is a leading cause of mortality in intensive care units and vasoactive drugs are widely used in septic patients. The cardiovascular response of septic shock patients during resuscitation therapies and the relationship of the cardiovascular response and clinical outcome has not been clearly described. We included adult patients admitted to the ICU with sepsis from Peking Union Medical College Hospital (internal), Medical Information Mart for Intensive Care IV (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD). The Blood Pressure Response Index (BPRI) was defined as the ratio between the mean arterial pressure and the vasoactive-inotropic score. BRRI was compared with existing risk scores on predicting in-hospital death. The relationship between BPRI and in-hospital mortality was calculated. A XGBoost's machine learning model identified the features that influence short-term changes in BPRI. There were 2139, 9455, and 4202 patients in the internal, MIMIC-IV and eICU-CRD cohorts, respectively. BPRI had a better AUROC for predicting in-hospital mortality than SOFA (0.78 vs. 0.73, p=0.01) and APS (0.78 vs. 0.74, p=0.03) in the internal cohort. The estimated odds ratio for death per unit decrease in BPRI was 1.32 (95% CI 1.20-1.45) when BPRI was below 7.1 vs. 0.99 (95% CI 0.97-1.01) when BPRI was above 7.1 in the internal cohort; similar relationships were found in MIMIC-IV and eICU-CRD. Respiratory support and latest cumulative 12-h fluid balance were intervention-related features influencing BPRI. BPRI is an easy, rapid, precise indicator of the response of patients with septic shock to vasoactive drugs. It is a comparable and even better predictor of prognosis than SOFA and APS in sepsis and it is simpler and more convenient in use. The application of BPRI could help clinicians identify potentially at-risk patients and provide clues for treatment. Fundings for the Beijing Municipal Natural Science Foundation; the National High Level Hospital Clinical Research Funding; the CAMS Innovation Fund for Medical Sciences (CIFMS) from Chinese Academy of Medical Sciences and the National Key R&D Program of China, Ministry of Science and Technology of the People's Republic of China.

Rational Pharmacotherapy in Type 2 Diabetes: Danish Data From 2002 to 2020 on Mortality, Diabetes- Related Outcomes, Adverse Events, and Medication Expenses.

Developments in pharmacotherapy and management of type 2 diabetes may have shifted the balance of treatment benefits versus harms and costs over the past decades. This study aimed to describe the trends in this balance. We followed the Danish population with type 2 diabetes between 2002 and 2020, analyzing their medication use in relation to treatment benefits (such as mortality and diabetes-related outcomes), adverse events, and medication costs. Using multivariate analyses, we adjusted for potential confounders, including age, sex, and socioeconomic status. The study included 461,805 individuals. From 2002 to 2020, the median age increased from 66 to 68 years, and the mean number of comorbidities increased from 5.2 to 8.8. The overall incidence of cardiovascular, renal, and other important adverse clinical outcomes decreased. Similarly, the rate of some adverse events, such as gastric bleeding, hypoglycemia, and falls declined, whereas the incidence of electrolyte imbalances and ketoacidosis increased. The average per-patient cost was reduced by 8%, but total medication expenses increased by 148% due to an expanding population size, lowered costs of most cardiovascular medications, and increasing costs for glucose-lowering drugs. Advancements in type 2 diabetes management have led to reduced risk of both diabetes-related outcomes and treatment harms, while maintaining relatively stable per-patient medication expenses. Although these trends are multifactorial, they suggest more rational pharmacotherapy. Still, increased risk of certain adverse events, along with increasing costs for glucose-lowering medications, underscores the need for ongoing vigilance and risk-benefit analysis.

Mitral Annulus Disjunction: A Comprehensive Cardiovascular Magnetic Resonance Phenotype and Clinical Outcomes Study.

Clinical importance of mitral annulus disjunction (MAD) is not well established. Characterize a population of MAD all-comers diagnosed by cardiac magnetic resonance imaging (MRI). Retrospective. MAD confirmed in 222 patients, age of 49.2 ± 19.3 years, 126 (56.8%) males. 1.5 T and 3 T/steady-state free precession and inversion recovery. Clinical history, outcomes, imaging, and arrhythmia data. MAD defined as a separation ≥2 mm between left ventricular myocardium and mitral annulus. Presence and pattern of late gadolinium enhancement (LGE) were analyzed. LGE in the papillary muscles and adjacent to MAD were identified as MAD related. Ventricular arrhythmias (VA) were grouped into non-sustained ventricular arrhythmias (NSVA) or sustained. Cardiovascular death assessed. Differences between baseline characteristics were compared. Univariate regression was used to investigate possible associations between ventricular arrhythmia and cardiovascular death with characteristics associated with the severity of MAD. A multivariable logistic regression included significant variables from the univariate analysis and was performed for MAD-related and global LGE. MAD extent 5.0 ± 2.6 mm. MV annulus expanded during systole for MAD ≥6 mm. Systolic expansion associated with prolapse, billowing, and curling. LGE present in 82 patients (36.9%). Twenty-three patients (10.4%) showed MAD-related LGE by three different observers. No association of LGE with MAD extent (P = 0.545) noted. Follow-up 4.1 ± 2.4 years. No sustained VA observed. In univariable analysis, NSVA was more prevalent in patients with MAD ≥6 mm (33.3% vs. 9.9%), but this was attenuated on multivariate analysis (P = 0.054). The presence of NSVA was associated with global LGE but not MAD-related LGE in isolation (P = 0.750). Three patients died of cardiovascular causes (1.4%) and none had MAD-related LGE. None died of sudden cardiac arrest. In patients referred for cardiac MRI, mitral valve dysfunction was associated with MAD severity. Scar was not related to the extent of MAD, but associated with NSVA. The risk of sustained arrhythmias and cardiovascular death was low in this population. 4 TECHNICAL EFFICACY: Stage 2.

Extrarenal Benefits of SGLT2 Inhibitors in the Treatment of Cardiomyopathies.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as pivotal medications for heart failure, demonstrating remarkable cardiovascular benefits extending beyond their glucose-lowering effects. The unexpected cardiovascular advantages have intrigued and prompted the scientific community to delve into the mechanistic underpinnings of these novel actions. Preclinical studies have generated many mechanistic theories, ranging from their renal and extrarenal effects to potential direct actions on cardiac muscle cells, to elucidate the mechanisms linking these drugs to clinical cardiovascular outcomes. Despite the strengths and limitations of each theory, many await validation in human studies. Furthermore, whether SGLT2 inhibitors confer therapeutic benefits in specific subsets of cardiomyopathies akin to their efficacy in other heart failure populations remains unclear. By examining the shared pathological features between heart failure resulting from vascular diseases and other causes of cardiomyopathy, certain specific molecular actions of SGLT2 inhibitors (particularly those targeting cardiomyocytes) would support the concept that these medications will yield therapeutic benefits across a broad range of cardiomyopathies. This article aims to discuss the important mechanisms of SGLT2 inhibitors and their implications in hypertrophic and dilated cardiomyopathies. Furthermore, we offer insights into future research directions for SGLT2 inhibitor studies, which hold the potential to further elucidate the proposed biological mechanisms in greater detail.

Predicting cardiovascular events with fluoropyrimidine chemotherapy using a standard cardiovascular risk calculator.

Fluoropyrimidine chemotherapy is important for treatment of many solid tumours but is associated with cardiotoxicity. The relationship of fluoropyrimidine-associated cardiotoxicity (FAC) with conventional cardiovascular (CV) risk factors is poorly understood, and standard cardiovascular risk scores are not validated in this context. Single-centre retrospective study of patients treated with fluoropyrimidine chemotherapy using electronic health records for cardiovascular risk factors (and calculation of QRISK3 score), cancer treatment, and clinical outcomes. FAC was defined by cardiovascular events during or within 3months of fluoropyrimidine treatment, and Cox regression was used to assess associations of CV risk and cancer treatment with FAC. One thousand eight hundred ninety-eight patients were included (45% male; median age 64years), with median follow up 24.5 (11.5-48.3months); 52.7% of patients were at moderate or high baseline CV risk (QRISK3 score >10%) Cardiovascular events occurred in 3.1% (59/1898)-most commonly angina (64.4%, 38/59) and atrial fibrillation (13.6%, 8/59), with 39% events during cycle one of treatment. In univariable analysis, QRISK3 score >20% was significantly associated with incident FAC (HR 2.25, 95% CI 1.11-4.93, P=0.03). On multivariable analysis, beta-blocker use (HR 1.04, 95% CI 1.00-1.08, P=0.04) and higher BMI (HR 2.33, 95% CI 1.04-5.19, P=0.04) were independently associated with incident CV events. Thirty-two of the 59 patients with FAC were subsequently rechallenged with fluoropyrimidine chemotherapy, with repeat CV events in 6% (2/32). Incident FAC did not affect overall survival (P=0.50). High BMI and use of beta-blockers are associated with risk of CV events during fluoropyrimidine chemotherapy. QRISK3 score may also play a role in identifying patients at high risk of CV events during fluoropyrimidine chemotherapy. Re-challenge with further fluoropyrimidine chemotherapy can be considered in patients following CV events during prior treatment.

Cardiovascular outcomes for people hospitalised with COVID-19 in Australia, and the effect of vaccination: anobservational cohort study.

To assess the frequency of clinical cardiovascular outcomes for people hospitalised with coronavirus disease 2019 (COVID-19), and the impact of vaccination. Observational cohort study. All index admissions of adults with laboratory-confirmed COVID-19 to 21 hospitals participating in the Australian Cardiovascular COVID-19 Registry (AUS-COVID), 4September 2020 - 11 July 2022. Frequency of elevated troponin levels, new arrhythmia, new or deteriorating heart failure or cardiomyopathy, new pericarditis or myocarditis, new permanent pacemaker or implantable cardioverter-defibrillator, and pulmonary embolism. impact of COVID-19 vaccination on likelihood of in-hospital death, intubation, troponin elevation, and clinical cardiovascular events. The mean age of the 1714 people admitted to hospital with COVID-19 was 60.1 years (standard deviation, 20.6 years); 926 were men (54.0%), 181 patients died during their index admissions (10.6%), 299 required intensive care (17.4%). Thirty-eight patients (2.6%) developed new atrial fibrillation or flutter, 27 (2.6%) had pulmonary embolisms, new heart failure or cardiomyopathy was identified in 13 (0.9%), and pre-existing cardiomyopathy or heart failure was exacerbated in 21 of 110 patients (19%). Troponin was elevated in 369 of the 986 patients for whom it was assessed (37.4%); in-hospital mortality was higher for people with elevated troponin levels (86, 23% v 23, 3.7%; P < 0.001). The COVID-19 vaccination status of 580 patients was known (no doses, 232; at least one dose, 348). The likelihood of in-hospital death (adjusted odds ratio [aOR], 0.38; 95% confidence interval [CI], 0.18-0.79) and intubation (aOR, 0.30; 95% CI, 0.15-0.61) were lower for people who had received at least one vaccine dose, but not the likelihood of troponin elevation (aOR, 1.44; 95% CI, 0.80-2.58) or clinical cardiovascular events (aOR, 1.56; 95% CI, 0.59-4.16). Although troponin levels were elevated in a considerable proportion of people hospitalised with COVID-19, clinical cardiovascular events were infrequent, and their likelihood was not influenced by vaccination. COVID-19 vaccination, however, was associated with reduced likelihood of in-hospital death and intubation. Australian and New Zealand Clinical Trials Registry, ACTRN12620000486921 (prospective).