bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCSK-9-inhibitor therapy improves endothelial function in high-risk patients with cardiovascular disease
Authors: Kannenkeril D , Bosch A , Kolwelter J , Striepe K , Pietschner R , Ott C , Schiffer M , Achenbach S , Schmieder R E 
Published: October 2022

Abstract

Background
Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyse the effect of evolocumab on endothelial function in patients with cardiovascular disease and on obligatory statin therapy.

Methods
This was a prospective, double-blinded, randomized, controlled, single center study including patients with cardiovascular disease (diagnosis of coronary artery disease, non-hemorrhagic stroke, transient ischemic attack or symptomatic peripheral artery disease) and treated with statins, similar to the inclusion criteria of the FOURIER study. Patients were consecutively randomized (1:1) to either evolocumab treatment (420mg was administrated in monthly intervals, twice during the study) or placebo. All patients underwent examination of endothelial function at baseline, and after 1, 4 and 8 weeks of treatment by a semi-automatic high-resolution ultrasound system (UNEX EF 18G; Unex Co., Nagoya, Japan). Endothelial function parameter such as flow-mediated vasodilation (FMD; vasodilator responsiveness), low flow-mediated vasocontriction (L-FMC; vasoconstrictor responsiveness) and vasoactive range (VAR; total vasomotor responsiveness) were measured.

Results
103 patients with a mean age of 66.2 (±7.7) years and a mean LDL-cholesterol of 98.2 (±19.1) mg/dl completed the study. 83.5% of the study population was known to have coronary artery disease. Endothelial function parameter (VAR) increased after 8 weeks of treatment with evolocumab compared to baseline (p=0.034), whereas there was no significant change at 1 and 4 weeks after treatment. Moreover, an improvement in VAR from baseline at week 8 was found with evolocumab compared to placebo (p=0.045).
In a subgroup analysis, in patients with age ≤67 years, lower systolic blood pressure (≤125 mmHg) or higher baseline LDL-cholesterol (&gt;95 mg/dl), significant evolocumab treatment effect was found in VAR improvement (p=0.006, p=0.049 and p=0.042, respectively) from baseline at week 8. No serious adverse event related to study medication occurred during the study.

Conclusion
Our data indicate that endothelial function could be improved with evolocumab treatment in high-risk patients with preexisting cardiovascular disease and on statin therapy. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): AMGEN GmbH
Regional strain score as prognostic marker of cardiovascular events. from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Pezel T , Bluemke D , Wu C , Lima J , Ambale Venkatesh B 
Published: October 2022

Abstract

Background
Left ventricular (LV) circumferential strain (Ecc) is an accurate indicator of regional myocardial function, particularly using the regional Ecc or layer-specific strain.

Purpose
To investigate the prognostic value of a regional strain score (RSS) for predicting the incident of heart failure (HF) and coronary heart disease (CHD) in a population without a history of cardiovascular disease at baseline.

Methods
In Multi-Ethnic Study of Atherosclerosis (MESA), 1,506 study participants (63.3±9.4 years, 54.6% men) underwent tagged magnetic resonance imaging for left ventricular circumferential strain (Ecc) analysis. Using −17% and −10% as Ecc cut-offs, each segment was rated from 0–2 points according to the Ecc value of each layer. The endo-Ecc, mid-Ecc, and epi-Ecc values from the 16-segment model were used to calculate three RSS: Endo-, Mid-, and Epi-RSS, respectively, which were defined as a percentage of good LV regional function. The Intramyocardial-RSS was the sum of these three RSS. Cox proportional models were used to evaluate the association between RSS and cardiovascular outcomes.

Results
After a median [IQR] follow-up of 15.9 [12.9–16.6] years, 122 hard CHD and 91 HF were observed. After adjustment, Mid-, Epi-, and Intramyocardial-RSS values &lt;50% were independently associated with HF (HR 1.43; 95% CI [1.08–2.87], p=0.004; HR 1.80; 95% CI [1.12–3.07], p&lt;0.001; and HR 2.01; 95% CI [1.19–3.20], p&lt;0.001). After adjustment, Endo-, Mid-, Epi-, and Intramyocardial-RSS &lt;50% were also independently associated with hard CHD (HR 1.31; 95% CI [1.03–1.51], p=0.04; HR 1.79; 95% CI [1.26–2.57], p&lt;0.001; HR 2.03; 95% CI [1.45–3.40], p&lt;0.001; and HR 2.28; 95% CI [1.51–3.53], p&lt;0.001).

Conclusion
Layer-specific regional Ecc, assessed by RSS, provides a robust, independent predictive value for incident HF and hard CHD in asymptomatic participants without any cardiovascular disease at baseline.

Funding Acknowledgement
Type of funding sources: None.
Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus
Authors: Ikonomidis I , Kountouri A , Pavlidis G , Katogiannis K , Thymis J , Pliouta L , Korakas E , Balampanis K , Bamias A , Lambadiari V 
Published: October 2022

Abstract

Background/Introduction
Patients with type 1 diabetes mellitus (T1DM) present signs of vascular and endothelial dysfunction earlier compared to healthy individuals. According to clinical studies, SGLT-2i favorably affect cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM). However, the data regarding the efficacy of SGLT-2i on cardiovascular markers in patients with T1DM are scarce.

Purpose
We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM.

Methods
We recruited in total 30 patients with T1DM and pour glycemic control who were under medication with insulin and received dapagliflozin (n=15) or intensification of insulin treatment (n=15) (control group). We measured at baseline and at four months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography.

Results
At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&gt;0.05). After four months treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−41%, p&lt;0.05), in PWV (−10%, p&lt;0.05), in cSBP (−6%, p&lt;0.05) and in GLS (+5%, P&lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +3%, PWV: +2%, cSBP: −2%, GLS: −3% at 4 months, P&gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after four months treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&lt;0.05).

Conclusions
Four-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

Funding Acknowledgement
Type of funding sources: None.
Unmasking systolic impairment in HFpEF by cardiovascular magnetic resonance derived hemodynamic force assessment: insights from the HFpEF stress trial
Authors: Backhaus S J , Uzun H , Roesel S F , Schulz A , Lange T , Evertz R , Kutty S , Hasenfus G , Schuster A 
Published: October 2022

Abstract

Background
The diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. Exercise-stress testing is recommended in case of uncertainty; however, this approach is time-consuming and costly. Since preserved EF does not represent normal systolic function, we evaluated cardiovascular magnetic resonance (CMR) comprehensive cardiac hemodynamic forces (HDF) analyses for an in-depth characterisation of cardiac function at rest.

Methods
The HFpEF Stress Trial (DZHK-17) prospectively recruited 75 patients with exertional dyspnea, preserved EF (≥50%) and signs of diastolic dysfunction (E/e' ≥8) on echocardiography. Patients underwent right heart catheterisation, echocardiography and CMR. 68 patients entered the final study cohort (HFpEF n=34 and non-cardiac dyspnea n=34 according to pulmonary capillary wedge pressure (PCWP)). HDF assessment included left ventricular (LV) longitudinal, systolic peak and impulse, systolic/diastolic transition, E-wave deceleration as well as A-wave acceleration forces. Two patients were lost to 24 months follow-up evaluating cardiovascular mortality and hospitalisation (CVH).

Results
HDF assessment revealed impairment of LV longitudinal force in HFpEF (15.8 vs. 18.3, p=0.035) attributable to impairment of systolic peak (38.6 vs 51.6, p=0.003) and impulse (20.8 vs. 24.5, p=0.009) forces as well as late diastolic filling (−3.8 vs −5.4, p=0.029). Impairment of early diastolic filling could be observed in HFpEF patients identified at rest only but not stress (7.7 vs. 9.9, p=0.004). Impaired systolic peak was associated to CVH (HR 0.95, p=0.016) and superior for CVH prediction compared to LV global longitudinal strain (AUC 0.76 vs. 0.61, p=0.048).

Conclusions
Assessment of HDF reveals impairment of LV systolic and diastolic function in HFpEF. The value of systolic HDF assessment exceeded that of conventional deformation imaging for CVH prediction.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research
The association of angiotensin-converting enzyme inhibitors and angiotensin 2 receptor blockers with renal protection in patients with SARS-CoV-2
Authors: Douen A D , Tan S T , Sukoo-Pertab M S , Bowser C B , Busari O B , Siu W S , Panetti P R , Kedarisetti S K , Romney W R , Ramdass R P , Lee W L , Juang G J , Toreli A T , Soni A S 
Published: October 2022

Abstract

Background
Kidney dysfunction is a prevalent disease that leads to many complications over time, such as hypertension, heart disease, and death. ACEI/ARBs are known to be renoprotective. However, few studies describe the association between ACEI/ARB use and kidney dysfunction in patients with SARS-CoV-2 infection.

Purpose
To explore the association between patients with SARS-CoV-2 and kidney dysfunction in patients taking an ACEI/ARB. We hypothesize a negative association between patients with SARS-CoV-2 taking an ACEI/ARB and kidney dysfunction.

Methods
A retrospective query between March 2020 and April 2021 was performed in patients 18 years and older who tested positive for SARS-CoV-2 using a polymerase chain reaction test. Patients were divided into two groups: kidney dysfunction and no kidney dysfunction. Kidney dysfunction was defined as any diagnosis of chronic kidney disease or acute kidney injury. Primary outcomes were all-cause mortality and hospitalization rate. Secondary outcomes included myocardial infarction (MI), hypotension, intubation, vasopressor use, ventricular tachycardia, and ventricular fibrillation. We used multivariate logistic regression to adjust for baseline characteristics.

Results
We identified 996 patients with kidney dysfunction and 22,106 without kidney dysfunction who tested positive for SARS-CoV-2. The incidence was 258 (25.9%) for ACEI/ARB use in patients with kidney dysfunction. Adjusted odds ratio (OR) for patients with kidney dysfunction was 5.705 (95% Confidence Interval [CI]: 4.554–7.146; p&lt;0.001) for hospitalization, 0.895 (95% CI: 0.707–1.135; p&lt;0.361) for patients taking ACEI/ARB, and 0.529 (95% CI: 0.333–0.838; &lt;0.007) for mortality in patients with kidney dysfunction who took ACEI/ARB. All secondary outcomes had significantly greater adjusted OR (p&lt;0.001), except for MI (p&lt;0.339), ventricular tachycardia (p&lt;0.697), and ventricular fibrillation (p&lt;0.060).

Conclusion
To date, the benefits of ACEI/ARB in SARS-CoV-2 patients have been controversial. While ACEI/ARB is known to have renoprotective properties, we did not find a significant association between ACEI/ARB and kidney dysfunction in patients with SARS-CoV-2. However, we found the use of ACEI/ARB in patients with kidney dysfunction to be associated with lower mortality. Therefore, clinicians should continue using this medication for its mortality benefits in patients with kidney dysfunction and its cardioprotective effects.

Funding Acknowledgement
Type of funding sources: None.
Trends in oral anticoagulant use in patients with atrial fibrillation in Belgium from 2013 to 2019: a nationwide cohort study
Authors: Grymonprez M , De Backer T L , Capiau A , Vauterin D , Mehuys E , Boussery K , Steurbaut S , Lahousse L 
Published: October 2022

Abstract

Background
Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly preferred over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management. However, differences in oral anticoagulant (OAC) prescribing according to patient's age, patient's sex and physician's specialty may be present.

Purpose
To investigate the incident and prevalent use of OACs, NOACs and VKAs, stratified by age, sex and prescriber, and factors associated with the choice of OAC on a full-population scale.

Methods
Using two Belgian nationwide healthcare databases, AF patients ≥45 years old with ≥1 OAC prescription claim between January 1st, 2013 and December 31st, 2019 were identified. OAC use was investigated per half-year with a repeated cross-sectional design, based on medication prescription claims on a day-to-day basis. Incident use was defined as the first OAC use during the study period in OAC-naïve AF patients, whereas prevalent OAC use was defined as at least 1 OAC dispensing during a specific half-year. Factors influencing NOAC versus VKA initiation were identified by multivariable logistic regression models.

Results
Among 448,661 included OAC-treated AF patients (260,184 prevalent NOAC and 188,477 prevalent VKA users), 297,818 were newly-treated (232,739 incident NOAC and 65,079 incident VKA users). The mean age of incident NOAC and VKA users was 76±10 and 71±12 years, and 48% and 47% were female, respectively. Incident OAC use ranged from 45–49 to 42–44 users/10,000 persons between 2013–2019, whereas prevalent OAC use increased from 337 to 435 users/10,000 persons. Incident and prevalent NOAC use exceeded VKA use since 2013 and 2015 respectively, and NOACs represented 92% of incident and 81% of prevalent OAC users in 2019. Apixaban was the most frequently used NOAC since 2016. NOACs were significantly more prescribed by cardiologists and to older patients, whereas VKAs were more initiated in patients with cardiovascular, renal and hepatic comorbidities. Prevalent OAC use increased less in women than men (+25% versus +33% between 2013–2019) and female subjects had a 5% significantly lower odds of NOAC versus VKA initiation than men after multivariable adjustment.

Conclusions
Prevalent anticoagulant use increased with 29% in Belgium between 2013 and 2019. However, potential (N)OAC underuse among female AF patients was observed.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO)
Antithrombotic strategies in antiphospholipid syndrome with arterial thrombosis: a systematic review and network meta-analysis
Authors: Attachaipanich T , Aungsusiripong A , Piriyakhuntorn P , Hantrakool S , Rattarittamrong E , Rattanathammethee T , Tantiworawit A , Norrasethada L , Chai-Adisaksopha C 
Published: October 2022

Abstract

Background
There was still a lack of consensus regarding optimal antithrombotic strategies in Antiphospholipid syndrome (APS) with arterial thrombosis.

Purpose
This Systematic review and Network meta-analysis (NMA) were conducted to evaluate the relative efficacy and safety of secondary thromboprophylaxis strategies in this setting.

Methods
We searched OVID MEDLINE, Web of Science and the Cochrane Controlled Register of Trials (CENTRAL) from inception to the March 1, 2022 without language restriction. Eligible studies were: i) included APS with arterial thrombosis; ii) treated with any of antiplatelet, warfarin, direct oral anticoagulants (DOACs) or a combination of those treatments, and iii) reported recurrent thrombotic events. Case reports or small studies which included less than 5 patients in each arm were excluded. Two investigators independently abstracted data and assessed risk of bias of included studies. A frequentist random-effects network meta-analysis was performed. All results were analyzed using the netmeta package in R, version 3.6.2.

Results
The database search resulted in 4076 results. After screening, 3998 studies were excluded. A total of 78 studies were included in full-text reviews. Finally, there were 12 studies (6 randomized and 6 non-randomized studies) included in this network meta-analysis, comprising 681 participants. Dual antiplatelet therapy (DAPT) and combined antiplatelet with warfarin were associated with lower risk of recurrent thrombosis with odds ratio (OR) 0.16 (95% CI 0.03 to 0.90) and 0.25 (95% CI 0.08 to 0.78) respectively comparing to single antiplatelet therapy (SAPT). DOACs and moderate-intensity warfarin were associated with higher recurrent arterial thrombosis with OR 12.59 (95% CI 2.03 to 78.19) and 5.25 (95% CI 1.17 to 23.48) respectively. There was no significant different major bleeding risk among antithrombotic regimens. The certainty of the evidences was very-low for all outcomes.

Conclusion
This network meta-analysis shows that a combination of antiplatelet with warfarin and DAPT were relatively effective antithrombotic strategies secondary prevention of recurrent thrombosis in arterial-thrombotic APS as compared to SAPT. However, there was still limited quality of evidence.

Funding Acknowledgement
Type of funding sources: None.
Thirty-days versus standard duration of dual antiplatelet treatment after percutaneous coronary interventions: a systematic review and meta-analysis
Authors: Apostolos A , Trigka A , Chlorogiannis D , Vasilagkos G , Chamakioti M , Spyropoulou P , Karamasis G , Dimitriadis K , Moulias A , Katsanos K , Tsioufis C , Toutouzas K , Alexopoulos D , Davlouros P , Tsigkas G 
Published: October 2022

Abstract

Background/Introduction
Abbreviation of duration of dual antiplatelet therapy (DAPT) (one or three months) has been recently proposed, especially for high-bleeding risk patients, after percutaneous coronary intervention (PCI) with drug-eluting stent (DES).

Purpose
The purpose of the specific systematic review and meta-analysis was to compare 30-days versus longer duration (≥3 months) of DAPT in patients undergoing PCI with DES, focusing on ischemic and bleeding events.

Methods
Three databases were screened for eligible randomized-control trials. The primary endpoint was the incidence of net adverse clinical events (NACE), as they were defined in each trial. Secondary endpoints consisted of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality, myocardial infraction, stroke, stent-thrombosis, repeat revascularization and major bleeding.

Results
We included 4 RCTs with a total of 26,576 patients; 13,282 patients were grouped in 30-days DAPT, while the remaining 13,294 were allocated in longer period of DAPT. One-month of DAPT did not significantly reduce NACE (odds ratio [OR]: 0.87, 95% confidence intervals [Cl]: 0.74–1.03); however major bleedings were significantly reduced by 22% (OR: 0.78, 95% Cl: 0.65–0.94). Mortality or ischemic events (stroke, myocardial infraction, revascularization and stent thrombosis) were not affected.

Conclusions
Thirty-days DAPT did not significantly affect NACEs. However, odds of major bleedings were reduced significantly by 22%. Mortality and ischemic events did not differ between the two arms. Thus, 30-days DAPT could be considered as a safe and feasible after PCI with DES in selected patients, especially those in high-bleeding risk. Forthcoming RCTs could shed light on the optimal duration of DAPT.

Funding Acknowledgement
Type of funding sources: None.
Sacubitril-valsartan activates pAMPK and reduces NLRP3, MyD88, cytokines/growth factors and DAMPs in doxorubicin-treated mice improving longitudinal strain and ejection fraction
Authors: Maurea N , Buccolo S , Iovine M , Paccone A , Luciano A , Barbieri A , Palma G , Maurea C , Quagliariello V 
Published: October 2022

Abstract

Background
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril-valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction.

Purpose
We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function

Methods
Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), LCZ-696 at 60 mg/kg (LCZ, n=6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100), pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.

Results
LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (p&lt;0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in LCZ-696-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in LCZ-696-DOXO group vs DOXO (p&lt;0.005).

Conclusion
In this preclinical study, LCZ-696 is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of Sacubitril-valsartan in prevention of cardiomyopathies induced by anthracyclines in cancer patients.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Ricerca Corrente, Ministero della Salute