bluuebunny/crossref_metadata_2025 huggingface dataset:
miRNAs profile as a signature for cardiovascular disease in long-term breast cancer female survivors: a pilot study
Authors: Greatti A , Sicurella M , Ghirardini C , Finello V , Mindicini N , Samiolo M , Sanz J M , Schirone A , Frassoldati A , Calabro' L , Passaro A , Neri L M , Raparelli V
Published: October 2024

Background/Introduction

Cardiovascular diseases (CVD) is a matter of immediate concern among long term breast cancer (BC) survivors. An early identification of those patients who are at higher risk of developing CVD is warranted to tailor prevention strategies and improve their quality of life.

Purpose

To identify whether a specific miRNA signature exists in breast cancer female survivors who develop CVD in a long term follow up.

Methods

We performed cross-sectional comparison of miRNA expression between female BC survivors (i.e. individual with a diagnosis of invasive ductal carcinoma who were free from cancer at 10-year follow up and without known CVD before BC diagnosis) with CVD (n=11) and without CVD (n=11) matched for age, BC grade, treatment received and traditional cardiovascular risk factors. CVD was defined as the incidence of established atherosclerotic cardio- or cerebro-vascular diseases (i.e., ischemic heart disease, carotid endarterectomy, stroke, heart failure), atrial fibrillation or venous thromboembolism. Thirteen miRNAs were selected since they were involved in either BC and CVD. On plasma derived samples, miRNAs expression profile analysis was performed by retro-transcription and real-time PCR assays, using miRNA-specific probes.

Results

The BC female survivors (mean age 73 years, 70% hypertension, 60% histological grade 2 and 3) were treated with surgery. The majority (76%) received hormone therapy after surgery according to the BC receptor expression. In half of the cohort, radiotherapy was performed. Those female BC survivors developing CVD experienced more commonly cerebral or cardiovascular atherosclerotic events (70%). As reported in Figure 1, some miRNAs analyzed (miR-19a; miR-21; miR-24; miR-125b; miR-195) are upregulated in BC survivors who developed CVD. Of note miR-19a, miR-21 (and miR-195) increase is so significantly relevant to consider these miRNAs as candidate biomarkers.

Conclusion(s)

In this discovery cohort, a specific miRNA profile signature identified female BC survivors experiencing CVD. Validation of such signatures is needed in a larger cohort as well as mechanistic studies to understand what is the pathophysiological link between the miRNAs identified and vascular health. Nevertheless these miRNAs in both cancer and cardiac diseases are mainly associated with promotion of cell proliferation and inhibition of apoptotic processes. The clinical implications of using a specific miRNA profile as a likely early biomarker of adverse cardiovascular events are indeed of great interest to better preserve BC survivors' health.Figure 1
Pregnancy and inherited cardiomyopathies: insights from specialized care
Authors: Sola Garcia E , Garcia Garcia A M , Casian M , Cauldwell M , Watt-Coote I , Sharma R , Marciniak A , Tome Esteban M
Published: October 2024

Background

Pregnancy and postpartum represent periods of increased risk of cardiovascular complications. Management of women with modified World Health Organization (mWHO) class II–III, III, and IV during pregnancy and around delivery should be conducted at an expert centre by a multidisciplinary team.

Purpose

Our objective was to analyze the impact of pregnancy on cardiomyopathy outcomes in a centre specialized in inherited cardiovascular conditions in the United Kingdom.

Methods

All women with cardiomyopathy referred due to pregnancy to our centre between 2016 and 2023 were retrospectively analyzed. Demographic, clinical, obstetric, genetic, electrocardiographic, and multimodal imaging variables were collected.

Results

Between 2016 and 2023, follow-up and delivery planning were initiated for 86 pregnancies in women with cardiomyopathies referred to our centre, resulting in 81 live births and 5 miscarriages, all in the first trimester. Among the full-term pregnancies, 17 (21%) were in patients in mWHO class I or II, 22 (27.2%) in II-III, 34 (42%) in III, and 8 (9.8%) in IV. The distribution of cardiomyopathy types among different mWHO classification is represented in Table 1. Women in mWHO class ≥ II-III had more pregnancy-related events than patients in mWHO I or II [28 (34.6%) vs 1 (1.2%); p = 0.004]. The most common complication in the first group was supraventricular tachycardia in 11 pregnancies (13.6%), followed by gestational diabetes in 9 (11.1%), left ventricular ejection fraction impairment in 4 (4.9%), preeclampsia in 3 (3.7%), and 1 (1.2%) ventricular tachycardia. One patient in the second group developed gestational diabetes. The distribution of the type of delivery among different mWHO classification is represented in Table 2. Only one patient with hypertrophic cardiomyopathy in mWHO II-III who underwent a caesarean section presented a post-delivery complication related to retroperitoneal haematoma, with no statistical significative differences between the groups (p = 0.604). 100% of the patients survived pregnancy and postpartum period.

Conclusions

Pregnant women with cardiomyopathy face an increased risk of adverse events. Despite the presence of cardiovascular and obstetric complications, careful monitoring at a specialized centre leads to favourable outcomes particularly concerning mortality rates for both the mother and fetus. This highlights the importance of a comprehensive risk assessment and meticulous pregnancy and delivery planning to ensure optimal maternal and fetal health.Table 1.Cardiomyopathy and mWHOTable 2.Type of delivery and mWHO
Proteomics in low CVD risk black women living with HIV: H-ART to Heart Study
Authors: Manmathan G P R , Acquaah V , Ngwu N , Johnson M A , Ponticos M A , Rakhit R
Published: October 2024

Background

39 million people worldwide are living with HIV (human immunodeficiency virus), acquired immune deficiency syndrome (AIDS)-related deaths have reduced by 51% since the peak in 2004. BWLWH represent 42% of those infected but only 9% are represented in clinical trials.

HIV/AIDS has been shown to be associated with the development of heart failure, pulmonary hypertension and myocarditis. Previous studies in asymptomatic PLWH have revealed a high burden of underlying CVD and subclinical disease.

The H-ART to Heart study is designed to examine potential signals and pathways of cardiovascular disease (CVD) in asymptomatic BWLWH with no traditional CV risk factors compared to HIV negative controls (-).

Methods

A cross-sectional study comparing asymptomatic BWLWH aged 35-55yrs (diagnosed >10 yrs, with undetectable viral loads) to HIV negative controls. Black African/Caribbean women without known CV risk factors (hypertension, hyperlipidaemia, diabetes, smoking, inflammatory arthritis, depression, severe mental illness) or hepatitis co-infection were included.

Assessment included blood pressure (BP), 10yr CVD risk calculation % (Q-Risk 3), bloods including lipids. A targeted discovery proteomics approach was used to evaluate 92 unique proteins using the O-link Target 96 Cardiovascular II panel.

Results

48 participants were recruited (23 BWLWH; 25 controls), mean duration of HIV was 17.6 years, mean duration of ART was 11.5 years, demographic details - Age 47.7± 44.7±; p=0.06, BP 125/77 v 123/79 ; p=0.89; BMI (kg/m²) 30.1±5.1 v 28.51±4.27 p=0.25; cLDL 3.49±1.22 v 2.42±0.74 p<0.02; Total Chol:HDL ratio 3.01±0.98 v 2.77±0.56 p=0.353; Q-Risk 3 1.92%±1.27 v 1.49%±1.12 p=0.219;

There were no significant differences in baseline data apart from higher mean cLDL in BWLWH.

Of the 92 proteins tested, 9 were significant in BWLWH (Figure 1). As demonstrated by the Heat map.

Conclusion

Data from our study of asymptomatic low risk BWLWH with no CVD risk factors indicates several pathways (Figure 2.) for further investigation in this previously under investigated vulnerable patient sub group. Whether this finding is of importance in CV risk assessment of BWLWH remains to be seen.
The long-term usage of statin prevents adverse events in patients with atrial fibrillation
Authors: Huang T C , Yap L H , Chen C Y , Lin H W , Lin S H , Li Y H
Published: October 2024

Background

The effectiveness of statins in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF.

Purpose

Our study aimed to investigate the relationship between statin use and cardiovascular outcomes in patients with newly-diagnosed AF.

Methods

This study used the National Health Insurance Research Database (NHIRD) in Taiwan. We enrolled 397,787 patients with AF from January 1st, 2012, to December 31st, 2020. Patients with AF were divided into 2 groups (statin user and statin non-user), and the risks of composite outcomes (ischemic stroke, hemorrhagic stroke and transient ischemic attack [TIA]), all-cause death and major adverse cardiovascular events (MACEs, which encompassed cardiovascular death, non-fatal myocardial infarction and heart failure hospitalization) were analyzed. Propensity score matching with time-dependent analysis was examined.

Results

We analyzed 288,958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin user had a lower risk of composite endpoint, which included ischemic stroke, hemorrhagic stroke and TIA. (adjusted hazard ratio, 0.92; 95% confidence interval, 0.88-0.95; p < 0.01) after adjusting for patients’ age, gender, CHA2DS2-VASc score, cardiovascular medications, and comorbidities. In regard to all-cause mortality, statin users exhibited a 62% risk reduction compared to statin non-users (hazard ratio, 0.38; 95% confidence interval, 0.37-0.39; p < 0.01). Statin use was also associated with reduced incidence of MACEs (hazard ratio, 0.70, 95% confidence interval, 0.68-0.71; p < 0.01). In the subgroups stratified by CHA2DS2 VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0-3 for composite endpoints but consistently reduced all-cause mortality and MACEs across all score categories.

Conclusions

Among patients with newly diagnosed AF, statin use was associated with a lower risk of ischemic stroke, hemorrhagic stroke, TIA, all-cause mortality and MACEs.
Interpretable machine learning model for predicting long-term cardiovascular mortality risk in chronic kidney disease patients using SHAP explainers
Authors: Wu W , Guo Y , Mo Y , Jia C , Tietge U J F
Published: October 2024

Background

Patients with chronic kidney disease (CKD) exhibited a pronounced burden of cardiac mortality. However, early prediction of cardiovascular mortality risk in CKD patients remains an unmet medical need.

Purpose

This study aimed to evaluate the performance of machine learning (ML) algorithms and identify the most influential factors in predicting long-term cardiac mortality among CKD patients.

Methods

Six ML models were developed, with the most effective one chosen for predicting and categorising patients into high-risk and low-risk groups based on the maximal Youden’s index. Differences in survival rates were assessed using the log-rank test on Kaplan-Meier curves. Cox regression analysis was employed to investigate the relationship between ML-predicted risk scores and mortality. Furthermore, the SHapley Additive exPlanations (SHAP) method was implemented to provide personalised explanations for model decisions.

Results

The auto-encoder (AE) model achieved the highest AUC of 0.94, with a sensitivity of 80.95% and specificity of 96.34%. Compared to individuals in low-risk group, those in high-risk group exhibited a significantly elevated risk of cardiovascular mortality (adjusted hazard ratio [HR]: 48.24; P <0.001). According to the SHAP model, age, C-reactive protein, blood urea nitrogen and hypertension were identified as the four most influential factors in the AE model.

Conclusions

Our study successfully developed an AE machine learning model for predicting 10-year cardiovascular mortality among CKD patients. The combination of ML model and SHAP aids doctors in understanding key features in the model, improving their insight into decision-making related to disease severity assessment, thus facilitating early preventive strategies in clinical practice.
The effect of the combined treatment with dulaglutide and dapagliflozin in arterial elasticity, cardiac function, albuminuria and endothelial thickness in type 2 diabetes mellitus after 12 months
Authors: Ikonomidis I , Thymis J , Korakas E , Kountouri A , Pavlidis G , Katogiannis K , Pliouta L , Raptis A , Lambadiari V
Published: October 2024

Background

The association between diabetes mellitus and diabetic nephropathy with vascular and endothelial properties is well established.

Purpose

In this study, we compared the effect of combined treatment with dulaglutide and dapagliflozin versus DPP-4 inhibitors on endothelial glycocalyx, arterial stiffness, myocardial function and albuminuria in patients with type 2 diabetes mellitus and albuminuria.

Methods

A total of 60 patients with type 2 diabetes mellitus and albuminuria were randomized to combined dulaglutide and dapagliflozin treatment (n=30) or DPP-4 inhibitors (DPP-4is, n=30). We measured at baseline and 4 and 12 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (c) global left ventricular longitudinal strain (GLS) (d) urine albumin-to creatinine ratio (UACR).

Results

Twelve months post-treatment, the combination of dulaglutide and dapagliflozin showed a greater improvement in all indices compared to DPP-4is, despite a similar reduction in glycosylated hemoglobin. Specifically, dual therapy showed greater improvements vs DPP-4is in PBR (2,10±0,31 to 1,93±0,23 μm vs 2,11±0,31 to 2,08±0,28 μm, p<0,001), in UACR (326±61 to 142±47 mg/g vs 345±48 to 306±60 mg/g, p<0,01), and in PWV (11,77±2,37 to 10,7±2,29 m/s vs 10,64±2,44 to 10,54±2,84 m/s, p<0,001), while only dual therapy showed improvement in cSBP (130,21±17,23 to 123,36±18,42 mmHg). Regarding GLS, both treatments were effective, but dual therapy showed a significantly higher percentage improvement compared to DPP-4is (18,19% vs 6,01%, respectively).

Conclusions

Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in vascular markers an albuminuria than DPP-4is in patients with type 2 diabetes mellitus and albuminuria. Early initiation of combined therapy as add-on to metformin should be considered in these patients.
Renal hyperfiltration as risk factor of major adverse cardiovascular events in patients with acute myocardial infarction
Authors: Kim W , Hwang H S
Published: October 2024

Objectives

While the interaction between heart and kidney potentially contributes the development of renal hyperfiltration (RHF), its clinical consequence of is not clear in patients with acute myocardial infarction (AMI).

Methods

A total of 9,561 AMI patients with estimated GFR (eGFR) ≥60 mL/min/1.73 m² were enrolled from a large nationwide, multi-center, prospective, observational cohort between November 2011 and December 2015. RHF was defined as eGFR >90th percentile after multiple adjustments. The primary endpoint was a combination of 3-year major adverse cardiovascular events (MACEs) after AMI treatment.

Results

The cumulative event rate of MACEs was significantly higher in patients with RHF. In multivariable Cox-regression analysis, RHF increased the 1.34-fold risk of MACE (95% confidence interval [CI] 1.12-1.62) compared to those without RHF. Patients with RHF had a significantly higher risk of all-cause mortality (hazard ratio [HR] 1.64; 95% CI 1.25-2.14) and cardiac death (HR 1.78; 95% CI 1.26-2.51). There was a linear correlation between the adjusted risk of MACEs and eGFR, with the risk increasing as eGFR exceeded approximately 100 mL/min/1.73 m². In the 1:1 propensity-score matched population, the cumulative event rate of MACEs, all-cause mortality, and cardiac death were consistently higher in patients with RHF (all p <0.05).

Conclusion

RHF was significantly associated with an increased risk of MACEs, all-cause mortality, and cardiac death following AMI compared to patients without RHF. Our study offers new insights into the risk stratification of AMI patients presenting with RHF.
Relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine in chronic kidney disease: a secondary analysis of the DANFLU-1 trial
Authors: Bartholdy K , Johansen N D , Janstrup K H , Modin D , Nealon J , Samson S , Salamand C , Loiacono M M , Jensen A M R , Landler N E , Claggett B L , Solomon S D , Gislason G H , Koeber L , Biering-Soerensen T
Published: October 2024

Background

Morbidity and mortality from influenza and cardiovascular disease occur frequently in persons with chronic kidney disease (CKD). Limited data exist on the effectiveness of high-dose influenza vaccination in persons with CKD.

Purpose

To assess the relative effectiveness of high-dose quadrivalent influenza vaccine (QIV-HD) vs. standard-dose quadrivalent influenza vaccine (QIV-SD) against clinical outcomes in persons with CKD.

Methods

In this secondary analysis of the DANFLU-1 trial, a randomized controlled feasibility trial to assess QIV-HD vs QIV-SD in the 2021-2022 influenza season, CKD was defined according to current KDIGO guidelines using data from laboratory registries and hospital diagnoses <6 years prior to vaccination. Prespecified outcomes in DANFLU-1 included time-to-first event of hospitalization for influenza or pneumonia, cardiovascular, cardiorespiratory, respiratory, and COVID-19 hospitalizations, all-cause hospitalization, and all-cause mortality. Outcomes were analyzed as both time-to-first and recurrent events. Cox proportional hazards regression was used to determine hazards ratios (HR) assessing the effectiveness of QIV-HD compared with QIV-SD for all time to first event analysis in CKD and non-CKD participants. Negative binomial regression was used to compute incidence rate ratios (IRR) for recurrent event analysis of all prespecified clinical outcomes. Interaction terms between CKD status and all outcomes were included to test for effect modification.

Results

Of 12,473 DANFLU-1 participants randomized to QIV-HD or QIV-SD, 1,878 had CKD. Among those with CKD, 14 were hospitalized with influenza or pneumonia. QIV-HD was associated with a lower incidence of hospitalization against influenza or pneumonia compared with QIV-SD (Figure 1: HR 0.25 [0.07-0.91], p 0.035). No other statistically significant differences were found in the time to first event analysis (Figure 1). In recurrent event analysis among persons with CKD, QIV-HD was associated with reduced risk of hospitalization for pneumonia (IRR 0.17 [0.04 – 0.70]; p 0.014), cardiorespiratory hospitalization (IRR 0.56 [0.32 - 0.99]; p 0.046, and all-cause hospitalization (IRR 0.74 [0.56 – 0.98]; p 0.038) (Figure 2). The presence of CKD at baseline did not modify the effect of QIV-HD compared with QIV-SD for any of the outcomes assessed.

Conclusion

In this secondary analysis of a large-scale pragmatic randomized trial, QIV-HD was associated with reductions in a broad range of clinical outcomes in persons with and without CKD. The potential superior effectiveness of QIV-HD compared to QIV-SD may therefore also apply to persons with CKD.
The efficacy and safety of GLP-1 agonists to modify cardiovascular morbidity in patients with obesity without diabetes mellitus: a meta-analysis involving 32,884 patients
Authors: Abouzid M , Al-Ajlouni Y A , Abuelazm M , Altobaishat O , Manasrah A , Turkmani M , Khan U , Tanashat M
Published: October 2024

Background

While the cardioprotective effects of glucagon-like peptide -1 (GLP-10) agonists are well-documented in diabetic patients, their impact on cardiovascular outcomes in patients with obesity without diabetes mellitus remains debated.

Purpose

This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of GLP-1 on cardiovascular outcomes in patients with obesity without diabetes mellitus.

Methods

A systematic review and meta-analysis synthesizing RCTs were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through December 26th, 2023. Dichotomous data were pooled using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI).

Results

We included 19 RCTs with a total of 32,884 patients. There was no difference between GLP-1 agonists and placebo regarding cardiovascular mortality (RR: 0.85, 95% CI [0.71- 1.01], P= 0.07). However, GLP-1 agonists significantly decreased the incidence of all-cause mortality (RR 0.83, 95% CI 0.72 to 0.94, p < 0.0001), non-cardiovascular mortality (RR 0.78, 95% CI 0.63 to 0.96, p = 0.02), and myocardial infarction (RR 0.73, 95% CI 0.62 to 0.87, p < 0.0001). Also, GLP-1 agonists significantly increased the incidence of any adverse events (RR 1.11, 95% CI 1.05 to 1.16, p < 0.0001), with no difference regarding the incidence of serious adverse events.

Conclusion

GLP-1 agonists not only demonstrated substantial benefits in reducing cardiovascular risks, including all-cause mortality and myocardial infarction, but also effectively promoted weight loss and improved lipid profiles and blood pressure control. However, their use is accompanied by a higher incidence of gastrointestinal adverse effects and heterogeneity in outcomes, highlighting the need for individualized treatment approaches.
Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis
Authors: Anastasiou V , Papazoglou A S P , Daios S D , Tsiartas E T , Zegkos T Z , Giannakoulas G G , Karamitsos T K , Ziakas A Z , Kamperidis V K
Published: October 2024

Background

Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking.

Purpose

The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR.

Methods

A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category.

Results

The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p <0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p <0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p <0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p <0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR.

Conclusions

RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR
The short-term prognosis of salvianolate use during hospitalization in patients with acute myocardial infarction
Authors: Guo R X , Zhang Y K , Hu S T , Gu T S , Jiang C , Zhang J K , Wu X , Liu X , Liu T , Chen K Y
Published: October 2024

Background

Salvianolate, derived from Salvia miltiorrhiza Bunge, is a traditional Chinese medicine known for its potential to promote blood circulation and eliminate blood stasis, often prescribed for cardiovascular system illnesses. This study aims to explore the impact of salvianolate treatment on the prognosis of patients with myocardial infarction during hospitalization.

Methods

This study included an acute myocardial infarction cohort from 71 secondary or tertiary hospitals between January 1, 2010 and June 30, 2023. Patients were divided into NSTEMI and STEMI groups. Clinical outcomes included cardiac death and major adverse cardiovascular and cerebrovascular events (MACCE, composite of cardiac death, myocardial infarction, ischemic stroke) within 30 days. Cox multivariable regression analyzed the association between salvianolate use and outcomes in STEMI/NSTEMI patients. Propensity score matching (PSM) adjusted for demographic and clinical differences between salvianolate and non-salvianolate groups. The matching factors including sex, age, Killip class, previous diseases (diabetes, hypertension, stroke, and renal insufficiency), previous percutaneous coronary intervention (PCI), in-hospital aspirin, clopidogrel, ticagrelor, lipid-lowering agents, nitrates, PCI, and thrombolytic therapy.

Results

A total of 76,157 STEMI patients and 74,373 NSTEMI patients were assessed. Among the STEMI group, 7,636 patients used salvianolate and 68,521 did not. Multivariate Cox regression analysis revealed that salvianolate use during hospitalization reduced cardiac death (aHR = 0.707, 95%CI = 0.623-0.803, P < 0.001) and MACCE (aHR = 0.730, 95%CI = 0.651-0.820, P < 0.001) at 30 days. These findings remained consistent in the matched population (n = 15,264) (cardiac death: aHR = 0.669, 95%CI = 0.569-0.786, P < 0.001; MACCE: aHR = 0.679, 95%CI = 0.586-0.787, P < 0.001). In the NSTEMI group, 6,461 patients used salvianolate, while67,912 did not. After matching, salvianolate use during hospitalization showed no significant difference in cardiac death and MACCE compared to not use.

Conclusions

Patients with STEMI treated with salvianolate exhibited improved short-term cardiovascular and cerebrovascular outcomes, while NSTEMI patients did not experience significant short-term prognosis enhancement.
Trimetazidine reduces stroke risk in ischemic atrial fibrillation: a territory-wide, propensity-matched study
Authors: Cheng Y T , Cheung B M Y , Yiu K H , Tse H F , Chan Y H
Published: October 2024

Introduction

Trimetazidine ameliorates myocardial ischemia via potentiating glucose oxidation. Whether such metabolic reprogramming protects against stroke risk in atrial fibrillation (AF) with ischemic heart disease (IHD) was unknown.

Purpose

To investigate the therapeutic impact of trimetazidine dihydrochloride on ischemic stroke in AF associated with IHD.

Methods

We collected data from a territory-wide clinical data registry (January 1999 to December 2020) with a coverage of 7.5 million population. 200,563 patients with IHD were identified. Amongst them, 13,092 (6.5%) had baseline AF (mean [SD] age: 79.7 [10.3] years, 44.8% female), and were identified as trimetazidine users (n=1,488) versus non-users (long-acting nitrates as control, n=11,604). Propensity matching at 1:1 was performed. Multivariable Cox regression was used to derive hazard ratios (HRs) for new-onset ischemic stroke.

Result

Over mean follow-up over 53.5 +/- 50.4 months, trimetazidine use was associated with a lower incidence of ischemic stroke (3.4% vs 7.6%, P<.001). Kaplan-Meier analyses showed trimetazidine use was associated with increased stroke-free survival period (Mean survival: 227.9 [4.9] versus 217.5 [3.6] months, Chi-square=39.0 P<.001). After adjusting for confounding factors, trimetazidine use remained an independent predictor of reduced ischemic stroke risk (adjusted HRs, 0.54, 95% CI, 0.37-0.78, P<.001).

Conclusion

Trimetazidine may reduce the risk of ischemic stroke in ischemic AF. These findings will need to be confirmed by randomized controlled trials.
Safety, tolerability, and basic pharmacokinetic parameters of AUX-001, a once-daily extended release nicorandil in healthy volunteers under fasting and fed conditions
Authors: Tigoer U , Chabowski D , Fonseca M
Published: October 2024

Introduction

Chronic-stable angina pectoris (CSAP) is one of the most common cardiovascular conditions in the developed world with a rising prevalence in both Europe and North America. Mounting evidence from chronic angina outcomes studies, including COURAGE, BARI, ORBITA and recently ISCHEMIA, has reemphasized optimized medical therapy (OMT) as first-line treatment for most chronic-stable angina pectoris (CSAP) patients over coronary revascularization. Yet, there has been a lack of development of new antianginal medications since 2006. To lessen polypharmacy and enable better long-term compliance in CSAP patients, AUX-001, a once-daily (QD), extended-release (ER) nicorandil is in clinical development for treating CSAP as an innovative, novel version of the immediate-release (IR) antianginal.

Objective

To test the safety, tolerability, and basic pharmacokinetic (PK) parameters of AUX-001 QD in fasting and fed conditions in healthy volunteers during this first-in-human phase 1a study.

Methods

16 healthy adult volunteers were enrolled. Vital signs (HR, BP, respiratory rate) and any adverse events were collected during screening, pre-dose, 1, 2, 6, 12, 24-h, and 48-h post-dose and at end-of-study for the two respective periods (fasting and fed).

Results

Evaluable information was available on 16 patients for fasting and 15 for fed conditions with one patient excluded due to protocol violation. No patient discontinued due to safety or tolerability. No severe AEs were recorded. AEs observed during period 1 included headaches (n=12), asymptomatic hypotension (n=3), palpitation (n=1) and nasal congestion (n=1). In period 2, leading AEs were headaches (n=11), neck pain (n=1) and decreased hemoglobin (n=1). Most AEs were mild and transitory and did not trigger medical intervention or discontinuation.

AUX-001 pharmacokinetics exhibited a reduced Cmax, a right-hand shift in Tmax, and an extension of T1/2 beyond 9 hours compared to the historical data of the commercially available IR nicorandil.

AUX-001 had a small, temporary effect on heart rate and systolic and diastolic blood pressure but within the normal compensatory haemodynamic steady-state stability. The peak effect with the current AUX-001 prototype was at 6 hours, independent of the food effect.

Conclusion

AUX-001 was safe and well tolerated. Initial vasodilator-induced headaches were manageable by using simple OTC NSAIDs and led to no dropouts. No patients discontinued due to AEs or tolerability issues. There were no lasting significant haemodynamic effects of AUX-001 beyond 24hours. PK parameters of AUX-001 are characteristic of an ER formulation. Observed pharmacokinetics indicates that the achieved T1/2 is substantially longer than with IR nicorandil (~1hour vs >9h) and shows promise for a potential once daily treatment of exercise induced chronic angina.AUX-001 Study Data ESC Abstract 2024
Common ECG abnormalities pose increased risks of out-of-hospital cardiac arrest
Authors: Hindborg M , Andersen M P , Sondergaard M M , Hasselbalch R B , Torp-Pedersen C
Published: October 2024

Background

It is known that 40%-60% of all sudden cardiac deaths occur as the first sign of unrecognized heart disease which poses a challenge in preventing early cardiac death (1). While many common ECG abnormalities have previously been associated with an increased risk of cardiac morbidity and mortality, knowledge of what abnormalities are associated with out-of-hospital cardiac arrest (OHCA) is lacking (2,3).

Purpose

To investigate the association between a range of common ECG abnormalities and the risk of subsequent OHCA.

Methods

From 2000 to 2020, patients acquiring an ECG at a Danish hospital or in an ambulance in Denmark were followed until either having OHCA, emigrating, death from other causes or end of study (01-01-2021), whichever came first. Only the index ECG and first occurrence of OHCA for each patient were considered for analysis. Data on patient age and gender were obtained through the Danish Civil Registration System. A multivariable Cox regression, adjusted for patient gender and age at ECG acquisition, was performed to assess the risk (hazard ratio [HR] with 95% confidence interval [95% CI]) of OHCA for various common ECG abnormalities. P-values less than 0.05 were considered significant.

Results

In total 2,037,003 patients were included, of which 26,446 (13.0%) had OHCA during follow-up after ECG acquisition. Patient characteristics and distribution of ECG abnormalities between the OHCA and non-OHCA patients are shown in Table 1. Patients with OHCA were older and more frequently male (both p < 0.001). ECG abnormalities were also generally more frequent among OHCA patients than non-OHCA patients. Median follow-up time for the entire cohort was 2063 days. The results of the multivariable Cox regression are shown in Figure 1. All assessed ECG abnormalities resulted in significantly higher risk of later OHCA with HR (95% CI) ranging between 1.0521 (1.0512-1.0531) and 1.0554 (1.0544-1.0563) when also adjusting for patient age and gender.

Conclusion

Common ECG abnormalities were associated with a significantly increased risk of OHCA. Further research is needed to investigate the mechanisms behind specific ECG abnormalities and OHCA occurrence and to determine the validity of ECG screening in preventing OHCA.Table 1Figure 1, SL = Sokolow-Lyon
Efficacy and safety of inclisiran in real-world clinical practice. Results from the CHOLINET Registry
Authors: Gargiulo P , Fontanarosa S , Marzano F , Cotticelli C , Crisci M , Marcucci R , Maloberti A , Sarullo F M , Galasso G , Musumeci G , Indolfi C , Varbella F , Calabro' P , Carugo S , Perrone-Filardi P
Published: October 2024

Background/Introduction

Inclisiran has been recently introduced in clinical practice. Thus, efficacy and safety data from real-world settings are limited.

Purpose

Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry including 36 Italian centers, designed to assess efficacy, safety, adherence and persistence of inclisiran treatment, and clinician’s behavior on LLT in very high CV risk patients with atherosclerotic CV disease and/or familial hypercholesterolemia (FH).

Methods

From November 2022 through February 2024, the Cholinet registry enrolled patients receiving inclisiran according to standard clinical practice. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at subsequent follow-up.

Results

We enrolled 668 patients in treatment with inclisiran (15.1% with FH, 30.7% female, mean age 63 years), Data on follow-up at 3 months (booster time) were available for 495 of them. At the time of inclisiran first prescription median LDL-C was 102 mg/dl and reached 51 mg/dl at the time of 3 months observation (50% mean reduction, 51 mg/dl absolute median reduction). None of the 495 patients reaching 3 months follow up missed the reinjection dose administration. Of 668 patients enrolled, 553 patients (82.7%) were on LLT, of them 107 (19.3%) were on ezetimibe alone, 67 (12.1%) on statin alone and 379 (68.5%) on a statin and ezetimibe combination. Of the enrolled patients, 45 (6.7%) were previously treated with evolocumab and 34 (5%) with alirocumab.

Among the patients evaluated at the 3-month follow-up, 307 patients (62%) achieved the LDL cholesterol target; of them, 450 (91%) were treated with inclisiran and statin±ezetimibe. Evaluating the distribution of the percentage reduction in LDL cholesterol values, a heterogeneity emerged that was partly explainable by the concomitant lipid-lowering therapy and partly by the previous exposure to PCSK9 inhibitors.

Conclusions

These preliminary data from the Cholinet Italian registry show that inclisiran effectively reduces (50%) LDL-C in real-world settings. The LDL-C target was achieved in 62% of patients; of them 91% were on lipid-lowering therapy, showing that combination therapy is necessary in most of these patients.
Empaglifozin modifies the arterial stiffness in type-2 diabetic patients: a preliminary report.
Authors: Feola M , Pastorini G , Anastasio F
Published: October 2024

Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrated beneficial effects on cardiovascular and renal events in patients with type 2 diabetes mellitus. The mechanisms underlying these effects are not fully elucidated. Aim of this study was to investigate whether empagliflozin is able to modify the arterial stiffness in type 2 diabetic patients.

Methods

Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed before and after adding empagliflozin to a traditional antidiabetic treatment in 16 consecutive T2DM outpatients folowed for 3 months. Arterial stiffness were evaluted using SphygmoCor ECEL measuring the pulse waveform of the arterial pulse moving from tha descending aorta to the femoral artery (PWV). Data obtained from the diabetic population has been compared to 16 T2DM outpatients not treated with SGLT2 inhibitors.

Results

In the two groups differences according gender distribution or duration of diabetes mellitus did not emerge. However the empagliflozin group was younger compared to controls (64.1±8.68 vs 74.45±8.13, P < 0.05). Empagliflozin treatment significantly decreased HbA1c after 12 weeks of treatment (7.9±0.78 vs 7.04±1.09%, P < 0.008.). After 12 weeks’ treatment, empagliflozin significantly improved PWV compared to controls not treated with SGLT2-i (ΔPWVV -0.68±1.1 vs 0.89±1,6 p <0.004, P = 0.0065 with age and HbA1c as covariates). Moreover body weight significantly decreased in the empagliflozin group (86.75±16.16 vs 81.71±16.5 kg, p =0.001) compared to controls (in whom remained unchanged) as long as BMI (30.48±5.4 versus 28.75±5.66 kg/m2, P < 0.002) compared to controls (in whom remained unchanged). Estimated glomerular filtration rate (eGFR) remained unchanged in the two groups during the study whereas urine Albumin to Creatinine ratio significantly improved using empagliflozin (17.8±46.8 vs 12.2±35.7 mg/mmol, P = 0.049).

Conclusion

In this ‘real clinical practice’ experience, the potential effect of empagliflozin treatment on arterial stiffness in T2DM patients was extensively investigated. Arterial stiffness was significantly decreased adding empaglifozin to the traditional treatment and this result has been obtained after 3-month. Significantly improvement in urine Albumin to Creatinine ratio might suggest an amelioration of endothelial function in those patients that could be involved in reducing arterial stiffness.
The role of sodium-glucose cotransporter 2 (SGLT2) inhibitors in epicardial adipose tissue modulation: a meta-analysis
Authors: Theofilis P , Vlachakis P K , Antonopoulos A S , Sagris M , Mantzouranis E , Sakalidis A , Oikonomou E , Siasos G , Tsioufis K , Tousoulis D
Published: October 2024

Introduction

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a groundbreaking class of antidiabetic medications, renowned for their glucose-lowering effects and cardiovascular benefits. Recent studies have suggested that SGLT2 inhibitors may extend their influence beyond glycemic control to impact adipose tissue physiology, particularly within the epicardial adipose depot. Epicardial adipose tissue (EAT), an actively secretory organ surrounding the heart, has been implicated in the modulation of cardiovascular risk.

Purpose

This meta-analysis aims to systematically review and synthesize existing literature on the effects of SGLT2 inhibitors on epicardial adipose tissue.

Methods

We performed a literature search for studies assessing epicardial adipose tissue before and after treatment with a SGLT2 inhibitor compared to a control group. We excluded reviews, editorials, case reports/case series, and studies that did not use SGLT2 inhibitors or did not have a control group for comparison. The main outcome of interest was the change in EAT volume/thickness at follow-up. Effect sizes are presented as standardized mean difference (SMD) with their corresponding 95% confidence intervals (CIs) and were pooled based on a random-effects model. The leave-one-out sensitivity analysis was used for further validation of the findings. Publication bias was assessed by funnel plot inspection and egger’s regression test.

Results

The literature search yielded 49 results. After application of the exclusion criteria, a total of 6 studies were selected for data extraction and inclusion in the meta-analysis. Accordingly, we detected that treatment with an SGLT2 inhibitor was associated with decreased EAT volume/thickness (SMD -1.79, 95% CI -2.91 to -0.66, p<0.01). There was substantial between-study heterogeneity (I2: 94%, p<0.01). Results remained robust even after exclusion of any single study. Funnel plot inspection and egger’s regression test did not indicate the presence of publication bias.

Conclusion

This meta-analysis suggests that SGLT2 inhibitors use is associated with a reduction in EAT volume/thickness, posing as a potential mechanism of their beneficial effects in heart failure outcomes.Figure
All cause mortality in people with type 2 diabetes using SGLT-2 inhibitors compared to DPP4 inhibitors using the danish registries
Authors: Yazdanfard P , Soerensen K , Pedersen-Bjerregaard U , Andersen M , Zareini B , Torp-Pedersen C
Published: October 2024

Background

The SGLT-2 inhibitors outcome trials such as EMPA-REG have had significant impact on the treatment and management of patients with type 2 diabetes. Using real world danish data simulating EMPA-REG criteria can demonstrate the efficacy of SGLT-2 in real world clinical settings.

Aim

The purpose of this study is to evaluate the efficacy of SGLT-2 in reducing all-cause mortality in people with type 2 diabetes (T2D) over a 5-year period, using real world data. We compared all cause mortality between those prescribed SGLT-2 and DPP4 inhibitors in a population resembling the EMPA-REG trial. DPP4 is selected as a comparator to SGLT-2 given it is known to be neutral with regards to cardiovascular disease (CVD).

Methods

Individuals were identified using Danish nationwide registries. This estimate was performed using in/exclusion criteria from EMPA-REG. We defined time zero as the first date the patient redeems either SGLT-2/DPP4. Individuals >=50 years of age with verified T2D and established CVD were included. CVD included myocardial infarctions, ischemic heart disease, stroke and heart failure. Individuals were only included if they had Hba1c at baseline > 53 mmol/mol (7.0%) The primary endpoint was all cause mortality. Survival was estimated using a Kaplan-Meier estimator in both arms. P values of less than 5% are considered significant.

Results

A total of 150.313 patients were identified to be on either DPP4-inhibitors or SGLT2 between 2012 and 2022. After applying EMPA-REG inclusion and exclusion criteria 15.461 patients remained (8518 on DPP4 and 6943 on SGLT2). The 5 year survival rate of SGLT2 and DPP4 was 0.780 and 0.657 respectively (p-value<0.0001).

Conclusion

In conclusion, we demonstrate, using EMPA-REG trial criteria in real-world data based on Danish nationwide registries, that five year mortality of people with T2D treated with SGLT-2 inhibitor was lower than those treated with DPP4 inhibitor.
A prospective analysis of the efficacy and safety of ethacizine during premature atrial contractions and premature ventricular contractions
Authors: Kuridze N , Etsadashvili K , Minadze E
Published: October 2024

Background

Ethacizine, a class Ic antiarrhythmic agent, is prescribed for managing severe or refractory supraventricular and ventricular arrhythmias, including premature atrial (PACs) and ventricular contractions (PVCs). Despite its use, there is a lack of substantial research exploring the therapeutic effects of ethacizine at present.

Purpose

The study evaluated the efficacy and safety of ethacizine in addressing PACs and PVCs, in cases where other antiarrhythmic medications proved ineffective.

Methods

We performed a prospective analysis of ethacizine treatment (50 mg. b.i.d.) for early (30-45 days) and late periods (150-210 days), in male (n=58; 59.2%) and female (n=40; 40.8%) patients aged ≥ 18 years (18-72 y.o; mean age 45 years), with 46 cases of PACs and 52 cases of PVCs, who had previously been treated with another antiarrhythmic medication (bisoprolol, metoprolol, sotalol, verapamil, amiodarone, or propafenone) and had not achieved the target rate of extrasystoles (≤1000/24h).

Results

The findings reveal a substantial decrease in the mean parameters of PACs during both, the early period (initial 6877 ± 2432, following 761 ± 341); (88,9%); t([45]) = [13,336], p = [< .001) and the late period (initial 6877 ± 2432, following 574 ± 294); (91,7%); t([45]) = [15,124], p = [< .001). The quantitative reduction in PACs reached a maximum of 93.8% in the early period (19406 PACs □ 1211 PACs) and 94.3% in the late period (19406 PACs □ 1105 PACs). The mean parameters of PVCs in the early period experienced a significant reduction (initial 3205 ± 1145, following 550 ± 194); (82,8%); t([51]) = [8,284], p = [< .001). Similarly, the mean PVC values in the late period exhibited a noteworthy decrease (initial 3205 ± 1145, following 490 ± 181); (84,8%); t([51]) = [8,553], p = [< .001). For PVCs, the maximum effect observed in the early period was 94.8% (18929 PVCs □ 989 PVCs), and in the late period, it reached 95% (18929 PVCs □ 950 PVCs). The target rate in the late period (≤1000/24h.) for PACs reached 89%, and for PVCs - 86% (Figure 1). Adverse effects were noted in a mere four subjects (4%). These events manifested as 2nd-degree AV block (Mobitz 1), sustained ventricular tachycardia, asymptomatic nonsustained polytopic ventricular tachycardia, and asymptomatic transient ST-segment elevation observed through 24-hour ECG holter monitoring.

Conclusion

A prospective study on ethacizine treatment (50 mg. b.i.d.) confirmed its effectiveness and safety in reducing PACs and PVCs. It demonstrated a sustained reduction in extrasystole occurrences for an extended period, achieving the target rate with minimal side effects. Ethacizine merits consideration for addressing extrasystolic arrhythmia, particularly in cases where other antiarrhythmic medications prove ineffective.Results of the study