bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immediate versus staged revascularisation in multivessel coronary disease: an updated meta-analysis
Authors: Von Renteln F , Hassan S , Szummer K , Edfors R , Venetsanos D , Kober L , Braunschweig F , Lewinter C 
Published: November 2020

Abstract

Background
Percutaneous coronary interventions (PCIs) are often aimed at the culprit vessel in acute coronary syndromes (ACSs) followed by revascularisation of other stenoses later in the index hospitalisation or shortly after discharge. PCI delay of non-culprit coronary vessels stenoses is supported by lower contrast fluid use and thrombocyte aggregation. Distinct coronary interventions increase the risk of both non- and coronary artery complications, e.g. acute abdominal and periphery artery bleeding, suggesting undertaking all PCIs at the same time.

Purpose
To assess the effect on mortality and re-myocardial infarction (MI) of immediate versus staged revascularisation in multivessel coronary disease, with the latter constrained to initial PCI of the culprit coronary vessel.

Methods
The syntax of “randomised controlled trial (RCT) & acute coronary syndrome & complete revascularisation” was undertaken in PubMed.
Clinical characteristics were gathered at the index hospitalisation. The intervention scenario was acute coronary syndrome or not.
Meta-analyses calculated relative risk (RR) reductions on outcomes of 1) mortality and 2) re-MI. Meta-regression assessed linear difference between interventional treatment benefits and baseline characteristics.

Results
A total of 148 studies was found. Of those, 8 was found eligible for further analyses and their baseline characteristics are shown in Table 1.
Comparison of immediate versus staged revascularisation on mortality was nonsignificant (RR, 1.19; 95% CI: 0.78–1.81, p=0.43) (Figure 1). The impact of Immediate vs staged revascularisation on re-MI was also nonsignificant (RR, 0.83; 95% CI: 0.44–1.55, p=0.56). Meta-regression found no associations between the outcomes and study characteristics (not shown).

Conclusion
The intervention of immediate compared to staged revascularisation assessed on outcomes of all-cause mortality and re-MI were nonsignificant.
Figure 1

Funding Acknowledgement
Type of funding source: None
Is there value in prescribing colchicine in coronary artery disease for secondary prevention: a meta-analysis of over 5,000 patients
Authors: Sunjaya A.F , Sunjaya A.P 
Published: November 2020

Abstract

Introduction
Coronary Artery Disease (CAD) is the single greatest cause of mortality and loss of disability adjusted life years (DALYs) worldwide. Inflammation plays a central role in the pathogenesis of atherosclerosis, with numerous evidence from prospective studies indicating that increasing C-reactive protein levels (hs-CRP) are independently associated with increasing risk of cardiovascular events. Colchicine, is an inexpensive, potent anti-inflammatory drug considered as a staple therapy for gout. Recent studies have shown that colchicine use may prove to be useful in the prevention of cardiovascular events.

Purpose
In patients with coronary artery disease (CAD) does administration of low dose colchicine lead to reduced all-cause mortality, cardiovascular risk and morbidity.

Methods
A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include all-cause mortality, cardiovascular events, CRP levels and prevalence of CRP levels less than 2.0 mg/L. Data synthesis and analysis was done using RevMan 5.3 using a random effects model.

Results
A total of 5 randomized controlled trials, representing 5,430 patients were included in this meta-analysis. Three trials administered colchicine 1 mg/day while the rest were assigned colchicine. 5 mg/day. Administration of colchicine in CAD patients was found to reduce all-cause mortality (RR=0.66, 95% CI: 0.30 to 1.46, p=0.31) and major adverse cardiovascular events (MACE) (RR=0.61, 95% CI: 0.25 to 1.47, p=0.27), although results were non-significant. Reduced CRP levels (Mean difference = −0.88, 95% CI: −1.76 to 0.01, p=0.05) compared to control group as well as a higher prevalence of patients with CRP levels &lt;2.0 mg/L were found (RR=2.27, 95% CI: 0.45 to 11.33, p=0.32), although results were non-significant.

Discussion
Few studies are available evaluating the benefits of low dose colchicine in CAD patients. The beneficial effects of colchicine has been proposed due to its ability to inhibit neutrophil chemotaxis which may reduce the risk of plaque instability. The use of colchicine for secondary prevention of CAD will require long-term use, which will require the need for preparations that address its intolerance (mostly gastrointestinal) to prevent early discontinuation of the medication.

Conclusion
There's limited evidence on the benefit of low dose colchicine in CAD patients. Further large scale randomized-controlled trials are needed, and its dose-response relationship ascertained before consideration of its use could be given in CAD patients.

Funding Acknowledgement
Type of funding source: None
Association of circulating proprotein convertase subtilisin/kexin type 9 concentration with prothrombin time in patients with chest pain
Authors: Peng J , Li J.J 
Published: November 2020

Abstract

Background
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has multiple roles in the development and progression of atherosclerosis. Recent studies have indicated an association of PCSK9 with thrombotic process.

Purpose
We aimed to examine whether there exists a relationship between plasma PCSK9 concentration and the most commonly coagulation parameters including prothrombin time (PT) and activated partial thromboplastin time (APTT).

Methods
A total of 2293 consecutive patients with angina-like chest pain who had no treatment of lipid-lowering drugs were enrolled in this study. The baseline clinical and laboratory data were collected. PT and APTT tests were performed. Circulating PCSK9 concentrations were determined by ELISA and classified into three subgroups according to their levels of PCSK9 tertiles. The relation of PCSK9 concentration to PT or APTT were analyzed.

Results
Firstly, we found that the patients with high PCSK9 levels trended to have lower PT and APTT (p&lt;0.0001, p=0.003) according to results of PCSK9 tertiles. Then, pearson correlation analysis showed that log-transformed PCSK9 concentration was negatively correlated with PT (r=−0.194, p&lt;0.0001) and was significantly but weakly related with APTT (r=−0.075, p&lt;0.0001). The stepwise multivariable regression analysis revealed that PCSK9 was independently related with PT after adjusting traditional atherosclerotic risk factors and coagulation parameters (β=−0.137, p&lt;0.0001; β=−0.121, p&lt;0.0001, respectively).

Conclusion
Circulating PCSK9 concentration was independently negative associated with PT, suggesting a potential link between PCSK9 and PT that may be involved in atherogenesis and atherothrombosis.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences
Intracoronary acetylcholine spasm testing: differences in epicardial coronary artery response between smooth and atherosclerotic coronary arteries
Authors: Gollwitzer R , Martinez Pereyra V , Seitz A , Bekeredjian R , Sechtem U , Ong P 
Published: November 2020

Abstract

Background
Coronary artery spasm is an established cause for angina pectoris. Epicardial coronary spasm may occur in patients with obstructed as well as unobstructed coronary arteries. Previous studies have suggested that epicardial plaque/atherosclerosis is a prerequisite for the development of epicardial spasm. The aim of the present study was to compare the results of intracoronary acetylcholine (ACh) testing in patients with signs and symptoms of myocardial ischemia with completely smooth versus atherosclerotic yet unobstructed epicardial arteries.

Methods
Between 2008 and 2016 a total number of 617 patients with signs and symptoms of myocardial ischemia yet unobstructed epicardial arteries (&lt;50% epicardial stenosis) was included in the present study (mean age 61±11, 61% female). All patients underwent invasive diagnostic coronary angiography followed by intracoronary ACh testing according to a standardized protocol. The ACh-test was considered “positive” in the presence of (a) angina, ischemic ECG shifts during the test and ≥75% focal or diffuse coronary diameter reduction (“epicardial coronary artery spasm”) or (b) ischemic ST-shifts and angina in the absence of epicardial spasm (“microvascular spasm”). All angiograms were assessed regarding any visible epicardial plaque/atherosclerosis in a blinded fashion and patients were categorized into those with completely smooth versus those with atherosclerotic coronary arteries. The analysis included 179 patients (29%) with epicardial spasm and 172 patients with microvascular spasm (28%). The remaining 266 patients (43%) had an uneventful or an inconclusive ACh-test result.

Results
There were 389 patients (63%) with completely smooth epicardial arteries. The remaining 228 patients (37%) had non-obstructive epicardial plaques &lt;50%. Patients with smooth arteries developed epicardial spasm in 24%, microvascular spasm in 32% and a negative/inconclusive test result in 44% of cases. Patients with atherosclerotic arteries developed epicardial spasm in 38%, microvascular spasm in 21% and an inconclusive/negative test result in 41% of cases. On univariate analysis the presence of epicardial atherosclerosis was associated with epicardial spasm (p=0.006) whereas this was not the case for microvascular spasm (p=0.094). Multivariate analysis revealed the presence of epicardial atherosclerosis (OR 1.921, CI 1.285–2.871, p=0.001) as well as female sex (OR 1.526, CI 1.024–2.274, p=0.038) as independent predictors for epicardial spasm.

Conclusion
In patients with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries the presence of epicardial atherosclerosis is an independent predictor for the occurrence of epicardial spasm but not microvascular spasm on acetylcholine testing.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): Robert-Bosch-Stiftung, Berthold-Leibinger-Stiftung
Prognostic impact of right ventricular overload in patients with acute coronary syndrome
Authors: Sato T , Ogihara Y , Kurita T , Mizutani H , Takasaki A , Moriwaki K , Tanimura M , Sawai T , Ito M , Dohi K 
Published: November 2020

Abstract

Background
Right ventricular (RV) overload is associated with adverse outcome in patients with chronic heart failure. However, its prognostic value in acute coronary syndrome (ACS) patients remains unknown.

Purpose
The purpose of this study was to investigate the prevalence and prognostic impact of right ventricular overload in ACS patients.

Methods
We studied 2797 ACS patients from Mie ACS registry, a prospective and multicenter registry in Japan. They were divided into 4 subgroups according to the severity of RV overload and the extent of Left Ventricle Ejection Fraction (LVEF) assessed by echocardiography before hospital discharge. High RV overload was defined as trans-tricuspid pressure gradient (TRPG) ≥40mmHg and preserved LVEF was defined as ≥50%. The primary outcome was defined as 2-year all-cause mortality. Median follow up duration was 730 days (1–2215 days).

Results
High RV overload was detected in 76 patients (2.7%). In basic patients characteristics, high RV overload patients were significantly older and higher killip classification than low RV overload patients (P&lt;0.01, respectively). Laboratory data in high RV overload patients showed lower hemoglobin level and higher serum creatinine level than those in low RV overload patients (P&lt;0.01, respectively).
Echocardiographic findings in high RV overload represented lower LVEF, higher rate of moderate or severe mitral regurgitation and left atrial enlargement than those in low RV overload patients (P&lt;0.01, respectively).
During the follow-up periods (median 730 days), 260 (9.3%) patients experienced all-cause death. Multivariate cox hazard regression analysis for all-cause mortality demonstrated that high RV overload was an independent poor prognostic factor in the entire study population. Among patients with preserved LVEF, high RV overload resulted in an increased risk of all-cause mortality compared to low RV overload (P&lt;0.0001).

Conclusion
In ACS patients, high RV overload strongly contributes to worsening of prognosis regardless of the extent of LVEF.
Kaplan-Meier survival curve

Funding Acknowledgement
Type of funding source: None
Platelets reactivity as a predictor of the extent of myocardial infarct damage and poor outcomes in STEMI patients undergoing primary PCI
Authors: Massalha E , Goitein O , Fardman A , Grupper A , Mazin I , Natanzon S , Beigel R , Matetsky S 
Published: November 2020

Abstract

Background
Despite optimized management of STEMI patients including primary PCI (PPCI) and use of novel anti-platelet agents, a substantial proportion still display a large infarct size and microvascular damage. The extent of MI and presence of microvascular damage as determined by cardiac MRI (CMR) are considered as powerful prognostic factors in predicting both early and long-term prognosis in those patients. Platelets reactivity has been implicated in pathogenesis of microvascular and subsequent myocardial damage including distal embolization, microvascular platelets plugging and inflammation.

Methods
We prospectively evaluated 105 consecutive STEMI patients, with no prior MI, who underwent PPCI. Patients underwent 2D-echocardiography within 48 hours of admission and cardiac MRI (CMR) 5±1 day post admission. All Patients were treated with dual antiplatelet agents and blood sample were analyzed for platelets reactivity (PA) at 72 hours post admission, using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists. Aspirin hypo-responsiveness was defined as AA-PA≥30%, and P2Y12 non-responsiveness as ADP-PA ≥50%. CMR was evaluated for late gadolinium enhancement (LGE) and microvascular obstruction (MVO), which reflects MI size and microvascular damage respectively. Both parameters were quantified as % of the LV mass. Major adverse cardiac events (MACE) were defined as the composite of death, MI, stroke, urgent revascularization and hospitalization due to either heart failure or bleeding during the first year post AMI.

Results
AA and ADP inhibition were 22±17, and 34±16 respectively. Aspirin hypo-responsiveness was associated with significantly higher extent of LGE (p=0.04) and MVO (p=0.003). A multivariate logistic regression analysis revealed that AA-PA hypo-responsiveness is an independent predictor of both MI size as reflected in LGE (OR 3.87; 95% CI: 1.47–10.5, p=0.031), and higher extent of microvascular damage as reflected by MVO% of LV mass (OR 3.6; 95% CI: 1.15–10.3, p=0.027). Patients with aspirin hypo-responsiveness were significantly more likely to sustain MACE (36% vs 12%, HR 4.13, 95% CI: 1.52–10.2, p=0.003). As opposed to AA related platelets reactivity, no significant correlation was demonstrated between ADP induced platelets reactivity and either measures of MVO or LGE.

Conclusions
In patients undergoing PPCI for STEMI, platelets reactivity in response to AA is an independent predictor of the extent of both myocardial and microvascular damage. Aspirin hypo-responsiveness is associated with higher rate of adverse events during 1-year follow-up.

Funding Acknowledgement
Type of funding source: None
Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome-dependent pyroptosis
Authors: Chen A , Chen Z.W , Qian J.Y , Ge J.B 
Published: November 2020

Abstract

Background
Coronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI) after coronary interventions, bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified.

Purpose
To determine whether NLRP3 inflammasome contributes to CME-induced cardiac injury and to investigate the effect of statin therapy on CME.

Methods
In vivo study, CME models were established in C57BL/6J mice by injecting 500,000 polyethylene microspheres (diameter 9 μm) into the left ventricle chamber with the occlusion of the ascending aorta. Mice with CME were treated with 40 mg/kg/d rosuvastatin orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Cardiac function was evaluated by echocardiography. Cardiac histological analysis was performed. The NLRP3 inflammasome and pyroptosis-related genes and proteins were detected. Cardiac injury was evaluated by Heidenhain's iron hematoxylin stain and serum lactate dehydrogenase (LDH) measurement. Cardiac reactive oxygen species (ROS) production and mitochondrial morphology were also determined. In vitro study, H9c2 myoblasts, stimulated with the classic NLRP3 inflammasome activators lipopolysaccharide (LPS) plus nigericin (Nig), were used to reveal underlying mechanisms of the rosuvastatin's effects.

Results
The expression of NLRP3, caspase-1 and interleukin-1β (IL-1β) were all increased and peaking at 3 days after CME. Mice treated with MCC950 and rosuvastatin showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum LDH level. Mechanistically, rosuvastatin decreased the expression of NLRP3, caspase-1, IL-1β and the pyroptosis executor Gasdermin D. Furthermore, reduced ROS level and alleviated mitochondrial damage were observed in rosuvastatin-treated mice. In vitro study, rosuvastatin effectively inhibited the activation of NLRP3 inflammasome induced by LPS and Nig in H9c2 cells, as evidenced by decreased expression of NLRP3, caspase-1, IL-1β and Gasdermin D. Flow cytometry revealed that rosuvastatin rescued LPS and Nig-induced caspase-1 activation from 22.2±1.6% to 4.09±0.85%. Meanwhile, the pyroptosis was also suppressed by rosuvastatin, indicated by the increased cell viability, decreased LDH and propidium iodide uptake. Similarly, rosuvastatin also reduced the level of ROS generation in vitro.

Conclusions
NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of rosuvastatin in CME, which is associated with regulating mitochondrial ROS.

Funding Acknowledgement
Type of funding source: None
Investigating sodium-glucose co-transporters 1 (SGLT1) in myocardium and its role in hyperglycaemia ischaemia-reperfusion injury
Authors: Almalki A , Harding I , Jasem H , Arjun S , Yellon D , Bell R 
Published: November 2020

Abstract

Background
Hyperglycaemia is a common finding in diabetic and non-diabetic patients presenting with ACS, and is a powerful predictor of prognosis and mortality. The role of hyperglycaemia in ischemia-reperfusion injury (IRI) is not fully understood, and whether the Sodium Glucose co-Transporter 1 (SGLT1) plays a role in infarct augmentation, before and/or after reperfusion, remains to be elucidated. However, diabetes clinical trials have shown SGLT inhibition improves cardiovascular outcomes, yet the mechanism is not fully understood.

Purpose
(1) Characterise the expression of SGLT1 in the myocardium, (2) determine the role of high glucose during IRI, (3) whether SGLT1 is involved in a glucotoxicity injury during IRI, and (4) whether inhibiting SGLT1 with an SGLT inhibitor may reduce infarct size.

Methods
RT-PCR and in-situ hybridization (RNAScope) techniques were used to detect SGLT1 mRNA expression in Sprague-Dawley whole myocardium and isolated primary cardiomyocytes. An Ex-vivo Langendorff ischemia-reperfusion perfusion model was used to study the effect of high glucose (22mmol) on the myocardium at reperfusion compared to normoglycaemia (11mmol). The mixed SGLT1&2 inhibitor, Phlorizin was introduced following ischaemia, at reperfusion and its effect on infarct size measured using triphenyltetrazolium chloride (TTC) staining.

Results
RT-PCR found SGLT1 mRNA is expressed in whole myocardium and in individual cardiac chambers. SGLT1 expression was not detected in isolated cardiomyocyte but it is detected in the non-cardiomyocyte population. Cardiomyocytes were found to express mRNA SGLT1 if incubated overnight. RNAscope detected SGLT1 mRNA within intact myocardium: not in the cardiomyocyte, but rather in a perivascular distribution. Importantly, hyperglycaemia (22mmol) at reperfusion increased infarct size (51.80±3.52% vs. 40.80±2.89%; p-value: 0.026) compared to normoglycaemia, and the mixed SGLT inhibitor, Phlorizin, significantly attenuated infarct size (from 64.7±4.2%to 36.6±5.8%; p-value&lt;0.01) when given at reperfusion.

Conclusion
We have shown that SGLT1 is present in the myocardium, but not expressed in cardiomyocytes. The cell type is yet to be determined, but the distribution of SGLT1 is perivascular. Hyperglycaemia appears augment myocardial infarction and inhibition of SGLT1&2 attenuates this increase. We suspect SGLT1 may plays a role in exacerbating the injurious effect of glucotoxicity during ischemia-reperfusion.

Funding Acknowledgement
Type of funding source: Foundation. Main funding source(s): British Heart Foundation
Left atrial strain is associated with left ventricular remodeling in patients with ST-elevation myocardial infarction
Authors: Legallois D , Hodzic A , Milliez P , Manrique A , Saloux E , Beygui F 
Published: November 2020

Abstract

Background/Introduction
Left ventricular remodeling (LVR) remains common and is associated with outcomes in patients with ST-elevation myocardial infarction (STEMI). Left atrial (LA) volume has been described as a predictor of outcomes in the latter population.

Purpose
To investigate the association between LA mechanical function using speckle tracking imaging and LVR at follow-up in STEMI patients.

Methods
Baseline 3D transthoracic echocardiograms were performed in 121 STEMI patients. LA global longitudinal strain was reported separately for the reservoir (LASr), conduit (LAScd), and contraction (LASct) phases. Follow-up echocardiograms were performed at 6 months.

Results
Mean age was 58.3±12.5 years and 98 (81%) were men. Baseline left ventricular ejection fraction (LVEF) was 46.8% [41.0, 52.9] and significantly improved to 52.1% [45.8, 57.0] at follow-up, (p&lt;0.001). A lower LASct was associated with a significant dilation of left ventricle at follow-up (%end-diastolic volume increase: −1.9% [−11.0, 15.2] in the two higher LASct tertiles group vs. 19.2% [5.0, 34.3] in the lower LASct tertile group, p=0.001). A higher %end-systolic volume increase at follow-up was associated with lower LASct as well: 12.6% [−16.2, 39.8] in the lower LASct group vs. −6.8% [−23.6, 14.4] in the two higher LASct tertiles group (p=0.004). Regarding LVEF, a low LVEF at follow-up was associated with the worst tertile of all LA strains (LASr, p=0.002; LAScd, p=0.01 and LASct, p=0.01).

Conclusion(s)
The three components of baseline LA strain were associated with LVEF at follow-up in patients with STEMI. Some of these components were also significantly associated with lower LVEF at baseline or predictive of a significant increase in left ventricular volumes during follow-up, indicating LVR.

Funding Acknowledgement
Type of funding source: None