bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of dapagliflozin in non-diabetic patients with primary anterior ST-elevation myocardial infarction initiated in early hospital period
Authors: Hayrapetyan H G , Petrosyan H H , Hayrapetyan L H , Tavaratsyan A R , Sargsyan M S 
Published: October 2024

Abstract

Background
The effectiveness of SGLT2 inhibitors has been proven in all types of chronic heart failure (HFpEF, HFmrEF, and HFrEF), regardless of the presence of diabetes mellitus. There are still no clear recommendations regarding the timing of SGLT2 inhibitor administration after myocardial infarction (MI) and its influence on prognosis. It can be assumed that it is appropriate to consider the possibility that, if started quickly after the presentation of acute MI, SGLT inhibition might enhance outcomes in patients.

Objective
This study aims to investigate the efficacy and safety of the SGLT2 inhibitor Dapagliflozin in primary anterior ST-segment elevation myocardial infarction (STEMI) initiated in early hospital period, irrespective of heart failure manifestation.

Methods
The study includes 124 non-diabetic patients with primary anterior STEMI who underwent primary PCI and had left ventricular ejection fraction (LV EF) ≤45% and NT-proBNP &gt; 900 pg/ml at symptom onset within 24 hours, regardless of heart failure symptom manifestation. Patients with cardiogenic shock were excluded. 62 patients received standard medical treatment including beta-blockers, ACE inhibitors (Control group), while the other 62 patients were administered the SGLT2 inhibitor Dapagliflozin 10 mg once a day during the first 48 hours of inpatient treatment, in addition to standard therapy (Dapa group). All patients were followed up for one year.
Echocardiography was performed during the first 24 hours. Echocardiography and NT-proBNP were repeated at the end of the year. The primary endpoint was the one-year heart failure hospitalizations and secondary endpoints included one year cardiovascular mortality and changes in NT-proBNP, plasma creatinine and glycosylated hemoglobin levels.

Results
The study shows a significant difference in heart failure hospitalization between the groups. In the Control group, it was 25.8%, and in the Dapa group, it was 8.1% (p = 0.008). Initially, there were no significant changes in NT-proBNP levels; 1152.2 ± 222.4 pg/ml in the Control group and 1197.3 ± 279.8 pg/ml in the Dapa group (p= 0.33). At the end of a year, NT-proBNP increased in the Control group (1827.4 ± 317.8 pg/ml), whereas in the Dapa group, it significantly decreased (613.5 ± 215.6 pg/ml) (p &lt; 0.01).
One-year cardiovascular mortality in the Control and Dapa groups was 9.7% and 4.8%, respectively(p=0.491). Other blood markers did not differ, and side effects were comparable during the in-hospital period as well as at the end of the year.

Conclusion
Early administration of Dapagliflozin among non-diabetic patients with primary anterior STEMI is associated with a significant decreasing of heart failure hospitalization rate and NT-proBNP level. Additionally, early administration of dapagliflozin does not impact on safety indicators.
AtheroVax: a peptide vaccine with a therapeutic effect in animal model of chronic inflammation
Authors: Kipshidze N , Kakabadze Z , Paresishvili T , Fareed J , Ramacciotti E , Iversen P 
Published: October 2024

Abstract

Background
Inflammation is a driver of atherosclerosis, but inflammatory mediators are essential components of the immune response. AtheroVax targets only pathogenic forms of sTNFR2 while preserving the membrane-bound (wild-type) TNFR2 and its contributions to a non-pathogenic immune response. We hypothesize that the vaccine mediated clearance of sTNRF2 will be more specific and offers long-term treatment options. The aim of this study is to investigate the therapeutic effect of an sTNFR2-targeting peptide (14 amino acid) vaccine, AtheroVax, in a rat model of acetic acid-induced colitis.

Methods
Two studies were conducted. In the first study 100 male outbred white Wistar rats (age 8 weeks, weight ~250 g) were used to evaluate a subcutaneous (SQ) injections of human sTNFR2 peptide sequence. In the second study 80 rats were used to evaluate SQ injections of the rat sTNFR2 sequence. After the adaptation period, the animals were randomly divided into treatment groups.
In study 1, group A (n = 30), phosphate-buffered saline (PBS), group B (n = 30), 25 μg of alum diluted in PBS, group C (n = 30), 25 μg of alum + 25 μg of peptide diluted in PBS, and group D (n = 10) no colitis controls. In study 2, group A (n = 25), phosphate-buffered saline (PBS), group B (n = 25), 25 μg of alum + 25 μg of rat sTNFR2 peptide, group C (n = 30), 25 μg of alum + 75 μg of rat sTNFR2 peptide, and group D (n = 5) no colitis controls. The animals were kept under standard vivarium conditions (temperature 22±2°C, relative humidity 50±5%, light/dark cycles 12 h/12 h). Animals were fed ad libitum standard laboratory chow and water under the supervision of trained personnel.

Results
The short 14 amino acid peptides administered prior to initiating colitis significantly improved the course of colitis in both studies by significantly (p&lt;0.05) reducing weight loss, fever, bleeding and diarrhea, and disease severity as well as providing a survival benefit (p&lt;0.05) in rats with colitis. AtheroVax also significantly (p&lt;0.001) reduced serum levels of TNF-α and IL-6. Histopathology evaluation reveals preservation of colon cellular architecture in vaccinated animals in both studies. Immunohistochemistry and examination of spleen and lymph nodes provides supporting evidence of the vaccine protection from chronic inflammation.

Conclusion
Our studies have shown that AtheroVax may be an effective therapeutic candidate for reducing chronic inflammation. These pre-clinical findings will provide a basis to further evaluate this novel vaccine in follow-up pre-clinical studies. A vaccine limiting the progression of atherosclerosis will greatly contribute to the reduction in morbidity and mortality from cardiovascular disease.
Platelet membrane coated r-SAK to improve thrombolytic efficacy by targeting thrombus
Authors: Hua R , Li M , Lin Q , Dong M , Gong X , Lin Z , Li Y , Li C , Wu T , Wang Q , Wu T , Zhou X , Yang F , Li C 
Published: October 2024

Abstract

Background
Thrombolytic therapy is one of the most effective treatments to achieve rapid thrombus clearance and recanalization of blocked vessels in thrombotic diseases. However, the application of thrombolytic strategy has been limited due to unsatisfied thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications.[1] With the development of nanotechnology and biotechnology, platelet membrane nanoparticles have been developed to enable the targeted delivery of thrombolytic agents to local thrombus sites.[2] Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology. In this study, platelet membrane coated r-SAK (PLT-r-SAK) was constructed, and its thrombolytic efficacy was evaluated in in-vitro and in-vivo experiments.

Purpose
We aimed to construct a thrombus-targeting agent of PLT-r-SAK and investigate its thrombolytic efficacy.

Methods
PLT-r-SAK was prepared by encapsulating r-SAK into platelet membrane vesicles using a membrane extrusion method. An in-vitro thrombolytic experiment was performed to examine the thrombolytic efficacy of PLT-r-SAK, and a totally occluded femoral artery thrombosis model of rabbit was developed to evaluate the in-vivo thrombolytic efficacy of PLT-r-SAK. The changes in femoral artery pressure were adopted to assess the vessel opening status. Besides, the effect of the antiplatelet drugs on the thrombolytic efficacy of PLT-r-SAK was explored. Finally, near-infrared fluorescence imaging system was used to verify the thrombus-targeting effect of PLT-r-SAK.

Results
PLT-r-SAK was firstly constructed, which exhibited a uniformly dispersed spherical morphology with a diameter of 185.8 ± 1.5 nm and a zeta potential of -26.1 ± 0.8 mV. In the in-vitro animal experiment, the thrombolysis rate of PLT-r-SAK was significantly higher than that of the same (low) dose and 4-fold (high) dose r-SAK (Figure 1a, 1b). In the in-vivo experiment, the initial recanalization time of PLT-r-SAK was significantly shorter than that of the low dose and high dose r-SAK, and the duration of the reperfusion time of PLT-r-SAK was prolonged compared to low dose and high dose r-SAK (Figure 1c). Another in-vitro experiment showed that the increased thrombolysis rate of PLT-r-SAK could be inhibited by platelet poor plasma (PPP) from aspirin- and ticagrelor-treated patients. Finally, both the in-vitro and in-vivo near-infrared fluorescence imaging showed significantly higher radiant efficiency in the PLT-r-SAK group as compared to the NS group (Figure 2).

Conclusions
Platelet membrane coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the platelet membrane and can be inhibited by aspirin- and ticagrelor-treated plasma.Thrombolytic efficacy of PLT-r-SAKThrombus-targeting evidence of PLT-r-SAK
Long-term outcomes of patients with apical hypertrophic cardiomyopathy: incorporation of a novel risk score
Authors: Desai M Y , Hajj-Ali A , Jadam S , Gaballa A , Xu B , Thamilarasan M , Popovic Z 
Published: October 2024

Abstract

Background
Apical hypertrophic cardiomyopathy (aHCM) is a subtype of HCM characterized by left ventricular hypertrophy predominantly in the apex. There is still limited data on factors associated with adverse outcomes in patients with aHCM.

Objectives
To a) describe the characteristics and b) develop a novel risk score associated with outcomes in aHCM patients.

Methods
A total of 462 patients (mean age 58±15 years, 68% male and 70% white) diagnosed with aHCM based on clinical, echocardiographic, and cardiac magnetic resonance (CMR) evaluation were included. The primary endpoint was all-cause death or aborted sudden cardiac death. Using the cox regression analysis, variables showing potential association with the composite endpoint were considered to develop an aHCM specific risk score.

Results
On echocardiography, the mean LV ejection fraction (LVEF) was 64±8%, and the mean LV mass was 223±72 g. A baseline CMR was performed in 246 (53%) patients, with delayed gadolinium enhancement in 170 (71%) patients with a mean percentage of 5±7%. Patients were followed-up for a mean of 68 months (range 1-248), with composite events occurring in 80 (17%) patients (death in 62 [13%] patients). Univariate Cox regression analysis identified age hazard ratio (HR) 1.06 (95% Confidence Interval or CI 1.04-1.08; p&lt; 0.001), apical aneurysm HR 2.32 (95% CI 1.24-4.34 p=0.008), lower LVEF HR 0.96 (95% CI 0.94-0.99 p=0.002), higher right ventricular systolic pressure (RVSP) HR 1.04 (95% CI 1.02-1.06 p&lt; 0.001), New York Heart Association Class IV HR 11.69 (95% CI 3.59-38.08 p&lt; 0.001) and the presence of Atrial fibrillation HR 1.77 (95% CI 1.14-2.76 p=0.012). An aHCM specific risk score was subsequently created (Figure 1), with good discrimination (c-statistic=0.75) and good calibration with expected to observed ratio of 1.02 and a calibration slope of 0.91 (p-value for difference between expected and observed probabilities =0.22). The risk score ranges between 0 and 8 points, with higher score associated with a higher rate of composite events (Figure 2).

Conclusion
We developed a novel risk score which demonstrated incremental prognostic value for hard events in aHCM patients.Risk prediction modelKaplan Meier event-free survival curves
Levosimendan improves the early prognosis of patients with Non ST-segment elevation myocardial infarction and Killip class &gt; II
Authors: Hu S T , Zhang Y K , Gu T S , Jiang C , Zhang J K , Wu X , Liu X , Liu T , Chen K Y 
Published: October 2024

Abstract

Background
Levosimendan is an inotropic agent known for its calcium-sensitizing myofilament effect and ATP-dependent potassium channel opening mechanism, which enhances myocardial contractility without increasing oxygen consumption. Despite its potential benefits, the impact of levosimendan on the prognosis of patients with myocardial infarction remains uncertain and requires further investigation through larger-scale studies.

Purpose
This study aimed to investigate the effect of levosimendan on the short-term prognosis of patients with Non-ST-segment elevation myocardial infarction (NSTEMI) and Killip&gt; II.

Methods
The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in the City from 2010 to 2023. A total of 12472 patients with NSTEMI and Killip &gt; II were included. Patients were divided into the levosimendan group and the non-leosimendan group based on whether levosimendan was used during hospitalization. Propensity score matching (PSM) was employed to balance covariates between the two groups. Multivariate Cox regression was used to evaluate the relationship between levosimendan and clinical outcomes. Covariates adjusted in PSM included age, sex, Killip class, early PCI, previous PCI, previous medical conditions (diabetes, hypertension, ischemic stroke, and chronic kidney disease), and medications during hospitalization (aspirin, clopidogrel, indobufen, ticagrelor, statins, cedilanid, recombinant human brain natriuretic peptide [rhBNP], milrinone, dopamine, dobutamine, and angiotensin converting enzyme inhibitor/angiotensin receptor blockers [ACEI/ARB]). The primary endpoint was major cardiovascular and cerebrovascular adverse events (MACCE), defined as the composite endpoint of cardiac death, myocardial infarction, and ischemic stroke within 3 months.

Results
The levosimendan group comprised 782 patients, while the non-leosimendan group included 11690 patients. After PSM, the covariates were balanced, resulting in 756 well-matched pairs. In PSM patients, the levosimendan group exhibited a significantly lower incidence of MACCE (aHR, 0.573; 95%CI, 0.466–0.704; p &lt; 0.001) and cardiac death (aHR, 0.500; 95%CI, 0.399-0.626; p &lt; 0.001). However, there was no significant difference in the incidence of myocardial infarction and ischemic stroke.

Conclusions
Levosimendan was associated with a lower incidence of MACCE within 3 months in patients with NSTEMI and Killip&gt; II, mainly driven by lower incidence of cardiac death. However, these findings are based on observational data and require confirmation through adequately powered, randomized, controlled trials.
The impact of high-intensity statin on 3-year clinical outcomes in elderly acute myocardial infarction patients underwent percutaneous coronary intervention with drug-eluting stents
Authors: Her A Y , Choi B G , Hyun S J , Rha S W , Kim Y H 
Published: October 2024

Abstract

Background
There is limited data on role of high-intensity statin for secondary prevention in elderly acute myocardial infarction (AMI) patients above 75 years old. Therefore, this study aimed to show the impact of high-intensity statin on 3-year clinical outcomes in elderly AMI patients (&gt;75 years) underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Methods
Among the 13,104 patients included in the Korea AMI registry (KAMIR)-National Institutes of Health (NIH), the elderly patients (&gt;75 years, n=2063) were divided into three groups according to statin treatment at discharge; the high-intensity statin group (n=521), the low/moderate-intensity statin group (n=1419), and the no statin group (n=123). The primary endpoint was 3-year composite of cardiac death and recurrent myocardial infarction (MI).

Results
During the 3-year clinical follow-up, the cumulative incidence of primary endpoint in the high-intensity statin group was similar to that of the low/moderate-intensity statin group (11.5% versus 12.5%; adjusted hazard ratio [aHR]: 1.053; 95% confidence interval [CI]: 0.780-1.423; P=0.739) and was significantly lower than that of the no statin group after adjustment (11.5% versus 22.0%; aHR: 2.433; 95% CI: 1.377-4.298; P=0.002). The incidences of major adverse cardiac events (MACE), target lesion failure (TLF), target vessel failure (TVF), procedure free cardiac events (PFCE), total death, cardiac death, and re-hospitalization due to heart failure (HF) in the high-intensity statin group were significantly lower than those of the no statin group after adjustment. However, the incidences of primary endpoint and other clinical events in the high-intensity statin group were similar to those of the low/moderate-intensity statin group.

Conclusions
In elderly AMI patients (&gt;75 years) underwent PCI with DES, high-intensity statin was associated with significantly reduced 3-year major clinical outcomes than no statin therapy group. This clinical benefit was similar to low/moderate-intensity statin therapy.
Exploring the long-term effects of dapagliflozin in patients with stable acute myocardial infarction and preserved ejection fraction through a propensity score matching study
Authors: Hsiao B , Lin W Y 
Published: October 2024

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 &lt; 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 &lt; 0.001) and age of diagnosis (hazard ratio = 1.063, 95% confidence interval =1.045-1.081, p &lt; 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
Association of PCI with outcomes in stable coronary artery disease
Authors: Price J , Tao M , Gupta S , Gier C , Pastena P , Ibtida I , Sharma A , Mann N 
Published: October 2024

Abstract

Background
The utility of percutaneous coronary intervention (PCI) in patients with stable symptomatic coronary artery disease (CAD) remains unclear. Although there has been recent literature to suggest that PCI may improve anginal symptoms, studies evaluating the association of PCI with clinical outcomes compared to optimal medical therapy (OMT) has yielded conflicting results.

Purpose
We performed a systematic review and meta-analysis evaluating the association of PCI compared to OMT with adverse cardiovascular outcomes in patients with stable CAD.

Methods
A literature search was performed using the databases Ovid MEDLINE, Embase, and Web of Science, identifying studies that evaluated the association of PCI with clinical endpoints in patients with symptomatic stable CAD. The primary endpoint was all-cause mortality. Secondary endpoints were recurrent acute myocardial infarction (AMI), cerebrovascular accident (CVA), and unplanned coronary revascularization. The search was not restricted to time or publication status.

Results
A total of 17 studies with 20,389 patients (11,294 PCI, 9095 OMT) met inclusion criteria. Mean follow-up duration was 3.98 years (ranging from 1 year to 6.5 years), mean age was 63.8, mean ejection fraction was 59%. All patients had symptomatic CAD with lesion severity &gt;50%. Compared to OMT, PCI was associated with lower risk of mortality on short-term (≤1 year) but not long-term (&gt;1 year) follow-up (OR 0.5, 95% CI 0.29-0.86; p=0.01; OR 0.68; 95% CI 0.42-1.12; p=0.88). PCI was not associated with lower risk of AMI or need for unplanned coronary revascularization (OR 1.02; 95% CI 0.73-1.44; p=0.90; OR 0.87; 95% CI 0.51-1.49; p=0.61). There was a trend toward lower risk of CVA in patients treated with OMT compared to PCI, however this was not statistically significant (OR 1.46; 95% CI 0.96-2.22; p=0.07).

Conclusions
The use of PCI in patients with stable CAD is associated with lower risk of all-cause mortality on short-term follow-up, however this association was not seen on long-term follow-up &gt;1 year. PCI was not associated with lower risk of AMI or unplanned revascularization and may be associated with increased risk of CVA compared to OMT. Additional high-quality studies are needed to further associate the utility of PCI in this patient population.Figure 1Figure 2