bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of sonothrombolysis using acoustically activated perflutren nanodroplets versus perflutren microbubbles
Authors: El Kadi S , Qian L , Zeng P , Lof J , Stolze E , Xie F , Kamp O , Van Rossum A.C , Porter T.R 
Published: November 2020

Abstract

Background
The use of intermittent high mechanical index (HMI) ultrasound impulses in combination with intravenously administered microbubbles (MB) has been shown to dissolve arterial and microvascular thrombi. The recent development of liquid droplets with nanoscale diameter from commercially available microbubbles may optimize thrombus permeation and subsequent thrombus dissolution.

Methods
Thrombi were formed from fresh porcine arterial whole blood mixed with thrombin, and placed in a vascular system mimicking branching epicardial coronary circulation (Figure 1A) at 37 Celsius and flow rate. A diagnostic ultrasound system with a tissue mimicking phantom was placed on top of the thrombus to simulate transthoracic echocardiography. Thrombus treatment consisted of a 10-minute infusion of either diluted nanodroplets (ND) or MB (same concentration) with intermittent HMI fundamental multipulse (3 usec pulse duration; FUS) or single pulse harmonic (HUS) impulses. All treatments were randomized and compared with HMI impulses alone. Efficacy was evaluated by percentage thrombus dissolution (%TD). Transmission electron microscopy (TEM) of residual thrombi after treatment was performed to examine for droplet permeation and resultant formed microbubble size.

Results
A relatively monodisperse nanodroplets size distribution was formed from microbubble cooled compression (mean diameter was 147±54 nm). A total of 60 porcine arterial thrombi were tested, 20 in each MB and ND treated group (20 control). Overall, there was a significant difference in %TD between ND treated thrombi (combining HUS and FUS HMI treated groups) versus MB treated thrombi and control (p&lt;0.0001 and p=0.02, respectively; ANOVA, Figure 1B). The highest %TD was seen in the FUS HMI treated ND group (mean 51±17%; Figure 1B). TEM of the DND treated group demonstrated significant expansion (diameters of 6 microns; Figure 1 C) of acoustically activated droplets embedded within the thrombi.

Conclusion
ND in combination with intermittent HMI ultrasound resulted in significantly greater thrombolysis compared to MB. In-vivo studies on nanodroplet mediated sonothrombolysis for vascular and microvascular thrombi should be performed with this modification of a commercially available microbubble.
Figure 1

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Theodore F. Hubbard Foundation
Multivessel versus culprit-only PCI in STEMI patients with multivessel disease: meta-analysis of randomized controlled trials
Authors: Feistritzer H , Jobs A , De Waha-Thiele S , Eitel I , Freund A , Abdel-Wahab M , Desch S , Thiele H 
Published: November 2020

Abstract

Background
Previous randomized controlled trials (RCTs) indicated a benefit of multivessel percutaneous coronary intervention (PCI) compared to culprit vessel-only PCI in ST-elevation myocardial infarction (STEMI) without cardiogenic shock.

Purpose
To perform a pairwise meta-analysis of RCTs, already including the recently published COMPLETE (The Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial, comparing multivessel PCI and culprit vessel-only PCI in STEMI patients without cardiogenic shock.

Methods
We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) comparing multivessel PCI with culprit vessel-only PCI in STEMI patients without cardiogenic shock and multivessel coronary artery disease. Only RCTs reporting mortality or myocardial reinfarction after at least 6 months following randomization were included. Hazard ratios (HRs) were pooled using random-effect models.

Results
Nine RCTs were included in the final analysis. In total, 523 (8.3%) of 6,314 patients suffered the combined primary endpoint of death or non-fatal reinfarction. This primary endpoint was significantly reduced with multivessel PCI compared to culprit vessel-only PCI (HR 0.63, 95% confidence interval [CI] 0.43–0.93; p=0.03). This finding was driven by a reduction of non-fatal reinfarction (HR 0.64, 95% CI 0.52–0.79; p=0.001), whereas no significant reduction of all-cause death (HR 0.77, 95% CI 0.44–1.35; p=0.28) or cardiovascular death (HR 0.64, 95% CI 0.37–1.11; p=0.09) was observed.

Conclusion
In STEMI patients without cardiogenic shock multivessel PCI reduced the risk of death or non-fatal reinfarction compared to culprit vessel-only PCI.

Funding Acknowledgement
Type of funding source: None
Long-term outcomes following percutaneous coronary intervention for patients with rheumatoid arthritis
Authors: Dawson L , Dinh D , Duffy S.J , Brennan A , Guymer E , Clark D , Oqueli E , Freeman M , Hiew C , Reid C , Ajani A.E 
Published: November 2020

Abstract

Background
Rheumatoid arthritis (RA) is the most common inflammatory arthritis and is associated with increased risk of cardiovascular events and mortality. Despite this, data regarding long-term outcomes following percutaneous coronary intervention (PCI) are limited.

Methods
We identified 756 patients with RA from the Melbourne Interventional Group PCI registry (2005–2018) and compared outcomes to the remaining cohort (N=38,579). Cox regression analysis was performed to assess risk of adverse cardiac events including long-term mortality (derived from linkage with the National Death Index [NDI]).

Results
Patients with RA were older (68.9±10.0 vs. 64.6±12.0 years) and more often female (40% vs. 23%), with higher rates of hypertension (70% vs 67%), previous stroke (9% vs 6%), peripheral vascular disease (9% vs 6%), obstructive sleep apnoea (10% vs 5%), chronic lung disease (22% vs 12%), prior myocardial infarction (32% vs 27%), and impaired renal function (eGFR&lt;60 ml/min/1.73m2 in 31% vs 24%), while rates of current smoking were lower (20% vs. 25%), all p&lt;0.05. Lesions were more frequently complex (ACC/AHA type B2/C in 61% vs 57%), required longer stents (&gt;20mm in 39% vs 35%), and rates of no reflow were higher (5% vs 3%), all p&lt;0.05. 30-day mortality was higher (4.4% vs. 3.3%, p=0.04) mainly owing to higher non-cardiac mortality (1.6% vs. 0.8%, p=0.01). National Death Index-linked long-term mortality was 28% vs. 19% (p&lt;0.01) with mean follow-up 4.6 vs. 5.4 years. Risk of 30-day and long-term mortality (including by indication subgroup) are presented in the Table.

Conclusions
Patients with RA undergoing PCI have more comorbidities and longer, more complex coronary lesions. After adjustment, risk of short-term adverse outcomes are similar, while risk of long-term mortality is higher, particularly among patients with acute coronary syndromes.

Funding Acknowledgement
Type of funding source: None
Early restenosis and late catch-up phenomenon after newer biodegradable- and durable-polymer drug-eluting stent implantations
Authors: Masumoto A , Ohya M , Murai R , Miura K , Shimada T , Amano H , Kubo S , Tada T , Tanaka H , Fuku Y , Kadota K 
Published: November 2020

Abstract

Background
It is yet to be known whether mechanisms underlying restenosis in newer-generation durable-polymer (DP) and biodegradable-polymer (BP) drug-eluting stents (DES) are different.

Purpose
This study aims to assess the incidences and predictors of early restenosis and late catch-up phenomenon after newer-generation durable-polymer (DP) and biodegradable-polymer (BP) DES.

Methods
Between 2010 and 2017, 13858 lesions in 6350 patients were treated with DES (4393 BP-DES, 9465 DP-DES). The early-term (within 1 year) and late-term (from 1 to 2 years) follow-up angiographies were scheduled. Late catch-up phenomenon was defined as in-stent restenosis (ISR) in lesions that evaded ISR within 1 year after stent implantation. ISR was defined as angiographic restenosis of more than 50%.

Results
The mean patient age was 71 years, and 76.7% were male. Early-term angiographies were performed in 10955 lesions (79.0%). Of those without early-term ISR, late-term angiographies were performed in 7771 lesions (56.1%). The incidences of mid-term restenosis and late catch-up phenomenon were 6.6% and 3.9%, respectively.
In the multivariate regression analyses, history of diabetes, hemodialysis and previous PCI were independent predictors of both early restenosis and late catch-up phenomenon. Also, some lesion characteristics such as chronic total occlusion, right coronary artery ostial lesion, small vessel (defined as reference diameter &lt;2.5mm), long lesion (defined as lesion length &gt;30mm) and treatment of ISR lesion were independent predictors of both early restenosis and late catch-up phenomenon.
Bifurcation lesion and heavily calcified lesion treated with rotablator were independent risk of early restenosis. Bypass graft lesion was an independent predictor of late catch-up phenomenon.
Early restenosis was observed less frequently in DP-DES than in BP-DES (6.3% versus 7.4%, P=0.012). On the contrary, late catch-up phenomenon was observed more frequently in DP-DES than in BP-DES (4.3% versus 2.9%, P=0.026).

Conclusions
Some lesion characteristics were independent predictors of early restenosis and late catch-up phenomenon after newer-generation DES implantation. The deployment of BP-DES resulted in more early restenosis and less late catch-up phenomenon compared to that of DP-DES.
Early Restenosis and Late Catch-Up

Funding Acknowledgement
Type of funding source: None
Applicability of ISCHEMIA to the daily practice of a Swiss University Hospital
Authors: Meier D , Mahendiran T , Muller O , Fournier S 
Published: November 2020

Abstract

Introduction
The ISCHEMIA trial found that an invasive strategy was not associated with a reduction in major adverse cardiovascular events when compared with optimal medical treatment (OMT) alone among patients with moderate/severe ischemia. However, given the extensive exclusion criteria of the study, we sought to investigate if these results would actually change our daily practice.

Methods
We performed a retrospective analysis of the last 1,000 consecutive PCIs undertaken in our university hospital in Switzerland. We applied the ISCHEMIA exclusion criteria to this population in order to estimate the proportion of patients that would have been excluded from the trial.

Results
Between October 2018 and November 2019, 1,000 PCIs were performed in a population with a mean age of 65.5 (IQR 51.0–76.0) years, of which 76.8% were men. Among these procedures, 603 (60.3%) were performed for an acute coronary syndrome (ACS) and 197 (19.7%) in the context of either an ACS within 2 months (n=131), or a PCI/CABG within 12 months (n=66) (Figure 1). A further 84 (8.4%) procedures were performed in patients with other high-risk features (ventricular arrhythmias, cardiac arrest, NYHA III-IV, eGFR &lt;30 ml/min or LVEF &lt;35%). Finally, 25 (2.5%) were performed in patients with unacceptable angina whilst on OMT, a cardiac transplant, a recent stroke, or another exclusion criterion. This left only 91 patients (9.1%) without any ISCHEMIA exclusion criteria. When considering only patients with SCAD (n=320), 229 (71.6%) would have been excluded due to the presence of at least one exclusion criterion.

Conclusion
In this retrospective analysis of 1,000 consecutive PCIs, the vast majority were performed in patients with at least one ISCHEMIA exclusion criterion. These results suggest that the impact of ISCHEMIA on the real-world practice of a medium-sized PCI center like ours is likely to be limited.
Figure 1

Funding Acknowledgement
Type of funding source: None
Temporal trends of acute kidney injury in patients undergoing percutaneous coronary intervention over a span of 12 years
Authors: Skalsky K , Bental T , Vaknin-Assa H , Assali A , Greenberg G , Codner P , Samara A , Ben Gal T , Eisen A , Kornowski R , Perl L 
Published: November 2020

Abstract

Background
Acute kidney injury (AKI) is a known complication following percutaneous coronary intervention (PCI), and is associated with higher rates of complications. We sought to determine the potential impact of temporal changes on the rates of AKI over time, as well as possible determinants of risk.

Methods
From a large prospective registry of patients undergoing PCI, 20,032 consecutive patients were assessed at two time periods: 2006–2012 and 2012–2018. Of these, included were cases for which data existed regarding change in creatinine levels from baseline to 48 hours after PCI. AKI was defined according to two methods- a relative elevation of ≥25% in serum creatinine or an absolute elevation of ≥0.5 mg/dL in serum creatinine at 48 hours.

Results
15,153 patients were available for final analysis, 7,913 in the first period and 7,240 in the second. Mean age was 65.0y and 66.0y (p&lt;0.01) and baseline creatinine was 1.08 mg/dL and 1.15 mg/dL respectively (p&lt;0.01, table 1).
AKI according to 25% relative rise in serum creatinine was documented in 11.1% in the early period and in 7.3% of the patients in the late period, p&lt;0.01. According to the definition of 0.5 mg/dL absolute rise in serum creatinine, respective rates were 3% and 2.9%, p=0.82 (figure 1). Multivariate analysis demonstrated a lower risk of AKI in the late period (OR- 0.72; CI 0.61–0.85, P&lt;0.01). Factors associated with risk of AKI included reduced ejection fraction (OR-0.98; CI 0.976–0.99, p&lt;0.01), older age (OR-1.01; CI 1.005–1.02, p=0.01) and female gender (OR- 1.73; CI 1.46–2.06, p&lt;0.01).

Conclusions
We have witnessed an improvement in the rates of post-PCI AKI over time. Further research is warranted, to further reduce peri-procedural AKI.
Figure 1. Change in the rates of AKI

Funding Acknowledgement
Type of funding source: None
Prognostic implication of baseline and 30-day anemia in patients with coronary artery disease undergoing percutaneous coronary intervention
Authors: Kang M.G , Cho S.Y , Kim K.H , Ahn J.H , Park H.W , Koh J.S , Park J.R , Park Y.W , Hwang S.J , Hwang J.Y , Jeong Y.H 
Published: November 2020

Abstract

Background
Anemia correlates with the risk of ischemic and bleeding event in coronary artery disease (CAD) following percutaneous coronary intervention (PCI).

Methods
We defined anemia by World Health Organization criteria (hemoglobin &lt;13 g/dL in men and &lt;12 g/dL in women). Major bleeding event was defined as Bleeding Academic Research Consortium (BARC) 3 or 5. Major adverse cardiovascular event (MACE) was defined as a composite of cardiovascular death, non-fatal myocardial infarct, and revascularization. The primary end-point was the MACE rate and the major bleeding rate.

Results
Among the 5,809 patients who underwent the PCI, 32.1% of the baseline anemia and 33.5% of the 30-day anemia were identified. With a median follow-up of 26.8 [15.9–42.3] months, and the MACE rate was 11.6% and the major bleeding event rate was 2.2%. 30-day anemia rather than baseline anemia showed a significant risk of MACE and major bleeding event (MACE, adjusted HR 1.28, p=0.036 vs. adjusted HR 1.09, p=0.389; major bleeding event, adjusted HR 2.72, p&lt;0.001 vs. adjusted HR 1.73, p=0.006) (Figure). The MACE and major bleeding event rate at 5-year was significantly increased in patients with 30-day anemia (18.4% vs. 12.1%, p&lt;0.001; 10.4% vs. 2.3%, p&lt;0.001).

Conclusion
Anemia during the first 30-day was strongly associated with higher rate of long-term MACE and major bleeding event. These findings could have a clinical relevance in making a pharmacologic strategies to avoid the future ischemic and bleeding event following PCI.

Funding Acknowledgement
Type of funding source: None
Oxidation of HDL in patients with coronary artery disease
Authors: Pagonas N , Mueller R , Weiland L , Jaensch M , Westhoff T.H , Buschmann I.R , Sasko B , Ritter O , Kelesidis T.H 
Published: November 2020

Abstract

The function of high-density lipoprotein (HDL) cholesterol may play a more important role in the prevention of cardiovascular disease compared to the concentration of the HDL. The aim of the present study is to assess a novel cell-free test to quantify oxidation of HDL and its association to coronary artery disease (CAD).
We performed a prospective trial by including patients undergoing elective cardiac catheterization and healthy controls. A total of 895 subjects were included. In 483 patients CAD was confirmed (CAD group) and in 241 patients CAD was ruled-out (no CAD). Control patients (n=171) had no known CAD, had no diabetes and were not smokers. HDL function was measured in serum samples by determining its HDL-lipid peroxidation by a novel fluorometric cell-free biochemical assay. HDL lipid peroxide content (HDLox) is adjusted for the HDL cholesterol and has no units.
Patients with confirmed CAD had higher levels of HDLox (0.92±0.58, no units) compared to patients with no CAD (0.8±0.46, no units) and controls (0.78±0.41, no units, p=0.003). HDL-Cholesterol was lower in the CAD group (50.7±17.7mg/dl) compared to no CAD (58.4±17.6mg/dl) and healthy subjects (59.1±15.9mg/dl, p&lt;0.001). HDLox was a strong predictor of coronary artery disease status (odds ratio for coronary disease 1.69; 95% confidence interval [CI], 1.24 to 2.38; P=0.001).
Oxidation of HDL, a metric of HDL function, measured by a cell-free biochemical assay, is increased in patients with CAD and is a predictor of the disease.
Logistic Regression analysis

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): Medical School of Brandenburg
Acquired von Willebrand Syndrome in left Impella supported cardiogenic shock patients
Authors: Vandenbriele C , Balthazar T , Engelen M , Adriaenssens T , Verhamme P , Peerlinck K , Janssens S , Jacquemin M 
Published: November 2020

Abstract

Background
Bleeding is a main cause of morbidity and mortality in critically ill cardiogenic shock patients, supported by short-term percutaneous mechanical circulatory support (pMCS) devices. Bleeding not only occurs because of obligatory heparin and antiplatelet therapy (both required in the prevention of pump and stent thrombosis) but possibly also results from device-related coagulopathy. Similar to long-term ventricular assist devices, mechanical shear-induced acquired von Willebrand syndrome (AVWS) might further increase the bleeding risk. Therefore, we aimed to investigate the effect of left Impella percutaneous continuous flow pumps on the development of AVWS due to shear-induced excessive cleavage of large vWF multimers by the metalloproteinase ADAMTS-13, resulting in loss of high-molecular-weight vWF multimers.

Methods
Between March 2019 and January 2020, all cardiogenic shock patients supported by a left Impella and referred to a single tertiary ICU were studied. Both vWF Antigen (vWF:Ag) and vWF:GPIbR (ristocetin-induced binding of vWF to a recombinant wildtype Glycoprotein Ib fragment) levels were measured by chemiluminescent immunoassays using an AcuStar (Werfen) assay to determine the vWF:GPIbR /vWF:Ag ratio (normal range ≥1.0). VWF multimer analysis was performed by electrophoresis. On-pump analyses were performed 12h after implantation and off-pump analyses 12h after Impella explantation. Patients who died on-pump were excluded because of lack of paired data after explantation.

Results
Eight left Impella patients (four Impella CP, four Impella 5.0) were analyzed for AVWS. The vWF:GPIbR /vWF:Ag ratio was &lt;1.0 in all patients on-pump (mean±SD 0.68±0.1 versus 1.1±0.15 off-pump (panel A; p=0.0018)) and thus AVWS was detected in all Impella-supported patients. The presence of AVSW was also confirmed by loss of large vWF multimers on-pump (panel B). Four patients (50%) had mucosal bleeds (epistaxis or gastrointestinal), none of them requiring transfusion. The mean rise in ratio 12h after pump removal was 0.35 which was also reflected by recovery of large multimers by electrophoresis (panel B).

Conclusions
Our data highlight the rapid onset and reversal of AVWS in all studied cardiogenic shock patients, supported by a left Impella pump. The determination of the GPIbR /vWF:Ag ratio with the AcuStar appears a reliable and faster test to detect AVWS as compared to vWF multimers electrophoresis. Further research into innovative pharmacological interventions (e.g. ADAMTS-13 inhibitors) should target pMCS-induced AVWS in an effort to reduce hemostatic complications in this critically ill ICU population.
AVWS in Impella supported patients

Funding Acknowledgement
Type of funding source: None
Intravenously delivered mesenchymal stem cells prevent MVO formation after myocardial ischemia/reperfusion injury
Authors: Xie J 
Published: November 2020

Abstract

Microvascular obstruction (MVO) after primary PCI is identified as an independent risk factor for prognosis in AMI patients. Inflammatory response induced by ischemia and reperfusion injury (I/R injury) was considered as one of main mechanisms for MVO formation. Mesenchymal stem cells (MSCs) are a unique stromal cell type that confers immunomodulatory effect in cardiac disease. Here we investigate whether intravenously and immediately delivered MSC could be used as potential therapeutic method to attenuate MVO formation. A cardiac-catheterization-induced porcine model of myocardial I/R injury was established, and allograft MSCs were delivered intravenously and immediately. Cardiac magnetic resonance imaging was performed 2 days and 7 days after operation to determine infarct area, MVO and cardiac function. We observed that the animals with allograft MSC delivering revealed decreased MVO and infarct size, as well as improved LVEF. In histology analysis, decreased myocytes area, fibrosis and inflammatory cell infiltration were observed in peri-infarct zone of animals with allograft MSC delivering. Meanwhile, the concentrations of IL-6, CRP and IL-1β in the serum were reduced in the allograft MSC group versus the control group. Flow cytometry indicated that decreased NK cells in the peripheral blood and ischemic heart tissue in the animals with allograft MSC delivering. In summary, we observed that allograft MSC delivering intravenously and immediately after myocardium I/R injury could attenuate MVO formation in porcine by NK cells depression.
Figure 1

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Natural Science Foundation of China