bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized, double blind, placebo-controlled, safety and efficacy study of dutogliptin in combination with filgrastim in early recovery post-MI: rationale, design and first interim analysis
Authors: Von Lewinski D , Merkely B , Buysschaert I , Schatz R.A , Nagy G.G , Kiss R.G , Henauer S , Wallner M
Published: November 2020

Background

Regenerative therapies offer new approaches to improve cardiac function after acute ST-elevation myocardial infarction (STEMI). Mobilization of stem cells and homing within the infarcted area have been identified as the key mechanisms for successful treatment. Application of granulocyte-colony stimulating factor (G-CSF) is the least invasive way to mobilize stem cells while DDP4-inhibitor facilitates homing via stromal cell-derived factor 1 alpha (SDF-1α). Dutogliptin, a novel DPP4 inhibitor, combined with stem cell mobilization using G-CSF significantly improved survival and reduced infarct size in a murine model.

Purpose

We initiated a phase II, multicenter, randomized, placebo-controlled efficacy and safety study (N=140) analyzing the effect of combined application of G-CSF and dutogliptin, a small molecule DPP-IV-inhibitor for subcutaneous use after acute myocardial infarction.

Methods

The primary objective of the study is to evaluate the safety and tolerability of dutogliptin (14 days) in combination with filgrastim (5 days) in patients with STEMI (EF <45%) following percutaneous coronary intervention (PCI). Preliminary efficacy will be analyzed using cardiac magnetic resonance imaging (cMRI) to detect >3.8% improvement in left ventricular ejection fraction (LV-EF). 140 subjects will be randomized to filgrastim plus dutogliptin or matching placebos.

Results

Baseline characteristics of the first 26 patients randomized (24 treated) in this trial reveal a majority of male patients (70.8%) and a medium age of 58.4 years (37 to 84). During the 2-week active treatment period, 35 adverse events occurred in 13 patients, with 4 rated as serious (hospitalization due to pneumonia N=3, hospitalization due to acute myocardial infarction N=1), and 1 adverse event was rated as severe (fatal pneumonia), 9 moderate, and 25 as mild. 6 adverse events were considered possibly related to the study medication, including cases of increased hepatic enzymes (N=3), nausea (N=1), subcutaneous node/suffusion (N=1) and syncope (N=1).

Conclusions

Our data demonstrate that the combined application of dutogliptin and G-CSF appears to be safe on the short term and feasible after acute myocardial infarction and may represent a new therapeutic option in future.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): This research is funded by the sponsor RECARDIO, Inc., 1 Market Street San Francisco, CA 94150, USA. RECARDIO Inc. is funding the complete study. The Scientific Board of RECARDIO designed the study. Data Collection is at the participating sites. Interpretation of the data by the Scientific Board and Manuscript written by the authors and approved by the Sponsor
Oral anticoagulant monotherapy compared to oral anticoagulant plus single anti-platelet therapy in stable ischemic heart disease with atrial fibrillation: a meta-analysis
Authors: Kumar A , Shariff M , Thakkar S , Doshi R
Published: November 2020

Introduction

Evidence for antithrombotic therapy regimen in patients with concurrent stable ischemic heart disease (SIHD) and atrial fibrillation (AF) is not well established. The ideal regimen needs to been balanced to prevent thrombotic and embolic events, without increasing the risk of bleeding tendencies. Two randomized control trials have been published studying oral anticoagulant monotherapy (OAC) as compared to oral anticoagulant plus single antiplatelet therapy (OAC+SAPT), of which one trial was terminated prematurely and was underpowered.

Purpose

We performed a meta-analysis of RCTs and observational studies comparing OAC monotherapy to OAC+ SAPT in SIDH patients with AF.

Methods

We performed a systematic search of the PubMed, EMBASE and Cochrane databases to identify relevant articles. The database search was performed from the inception of the databases to January 2020. Inclusion criteria were RCTs and observation studies comparing OAC to OAC+SAPT in SIDH patients with AF and reporting time to event outcomes of major bleeding or cardiovascular mortality. The definition of major bleeding as per the definition provided by individual studies. Two authors independently performed data extraction to check for reproducibility. We used inverse variance method with random effect model to calculate hazard ratio (HR) with 95% confidence interval (CI). Statistical heterogeneity was calculated using Higgins I2 statistics. All statistical analysis was performed using RevMan Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).

Results

Seven studies (2 RCTs and 5 observational studies) were included in the final analysis. OAC+ SAPT as compared to OAC monotherapy in patients with SIHD and AF was associated with a higher incidence of major bleeding [HR: 1.59, 95% CI: 1.36–1.85, P value<0.05, I2: 0%] [Figure 1, Panel A]. OAC+SPT as compared to OAC monotherapy was associated with similar incidence of cardiovascular mortality [HR: 1.07, 95% CI: 0.86–1.33, P value= 0.55, I2: 32%] [Figure 1, Panel B]. There was no statistical heterogeneity associated with either pooled estimates.

Conclusion

OAC monotherapy as compared to OAC+SAPT in patients with SIHD and AF was associated with a lower incidence of major bleeding and similar incidence of cardiovascular mortality.

Figure 1

Funding Acknowledgement

Type of funding source: None
Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes
Authors: Said A , Van De Vegte Y.J , Verweij N , Van Der Harst P
Published: November 2020

Background

Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes (T2D). However, whether these associations are causal remains unknown.

Objectives

This study aimed to identify genetic variants associated with caffeine intake, and to investigate possible causal links between genetically determined caffeine intake and CAD or T2D. Additionally, we aimed to replicate previous observational findings between caffeine intake and CAD or T2D.

Methods

Genome wide associated studies (GWAS) were performed on caffeine intake from coffee, tea or both in 407,072 UK Biobank participants. Identified variants were used in a two-sample Mendelian randomization (MR) approach to investigate evidence for causal links between caffeine intake and CAD in CARDIoGRAMplusC4D (60,801 cases; 123,504 controls) or T2D in DIAGRAM (26,676 cases; 132,532 controls). Observational associations were tested within UK Biobank using Cox regression analyses.

Results

Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2D compared to no or high intake, with the lowest risks at intakes of 120–180 mg/day from coffee for CAD (HR=0.77 [95% CI: 0.73–0.82; P<1e-16]), and 300–360 mg/day for T2D (HR=0.76 [95% CI: 0.67–0.86]; P=1.57e-5). GWAS identified 51 novel genetic loci associated with caffeine intake, enriched for central nervous system genes. In contrast to observational analyses, MR analyses in CARDIoGRAMplusC4D and DIAGRAM yielded no evidence for causal links between caffeine intake and the development of CAD or T2D.

Conclusions

MR analyses indicate caffeine intake might not protect against CAD or T2D, despite protective associations in observational analyses.

Manhattan_plot_CaffeineIntake

Funding Acknowledgement

Type of funding source: None
Influenza vaccination and in-hospital mortality in patients with acute myocardial infarction with history of prior PCI or CABG: a nationwide cohort analysis
Authors: Patil S.P , Gonuguntla K , Rojulpote C , Borja A.J , Zhang V , Koa B , Kumar M
Published: November 2020

Introduction

Influenza vaccination is associated with lower risk of death as well as major adverse cardiovascular events, including acute myocardial infarction (AMI), heart failure and stroke.

Purpose

The impact of Influenza vaccination on in-hospital mortality in patients with AMI with a prior history of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) is largely unknown. We hypothesize that such individuals who develop AMI have better outcomes if they had received influenza vaccine.

Methods

We analyzed the United States National Inpatient Sample Database from 2010–2014 to identify patients with primary discharge diagnosis of AMI (STEMI, NSTEMI) with a history of prior PCI or CABG. In this cohort, patients with influenza vaccination were identified using ICD-9 code V04.81. The primary outcome was in-hospital mortality. Chi-square test and multivariate regression model controlling for age, gender, race, type of AMI and co-morbidities were employed for statistical analysis.

Results

A total of 495,619 patients with ACS were identified who had prior PCI or CABG and 6525 had positive influenza vaccination status. Influenza vaccination was independently associated with lower risk of in-hospital mortality in patients with AMI (aOR = 0.253, 95% CI: 0.196–0.328; p<0.001).

Conclusion

Vaccination against influenza was associated with lower risk of in-hospital mortality in patients with prior PCI or CABG who developed AMI.

Figure 1

Funding Acknowledgement

Type of funding source: None
Impact of pre-treatment with acetylsalicylic acid on the severity of a first myocardial infarction in diabetic patients
Authors: Moura A , Saraiva M , Carveiro N , Domingues K , Martins V.P
Published: November 2020

Introduction

Diabetes Mellitus (DM) is one of the main risk factors for cardiovascular disease (CVD). Guidelines on the use of acetylsalicylic acid (ASA) for primary prevention of CVD in this population are conflicting. A potential reduction in the severity of a first episode of Acute Myocardial Infarction (AMI) could be seen has an additional argument for the use of ASA in primary prevention. Aim: To evaluate the impact of prior intake of ASA on the presentation, severity and short-term prognosis of AMI in diabetic patients without history of CVD.

Methods

Retrospective analysis of diabetic patients without previous evidence of CVD diagnosed with type 1 AMI between January 2002 and December 2018, inserted in a multicentric registry of acute coronary syndromes. Patients were dichotomized according to whether or not they were taking ASA prior to the index event. Groups were compared according to clinical, analytical and imaging endpoints.

Results

A total of 2596 patients were included, predominantly men (66.4%), with a mean age of 68±12 years old. Patients on ASA (19.7%) were significantly older (71±10 vs. 67±12, p<0.001) and had a higher prevalence of hypertension (89.2% vs 77.9%, p<0.001), dyslipidaemia (69.8% vs. 61.1%, p<0.001) and chronic kidney disease (10.6% vs. 4.9%, p<0.001). Overall, there was a lower prevalence of AMI with ST-segment elevation (36.5% vs. 50.8%, p<0.001) in patients on ASA. However, the same group of patients had a significantly higher probability of evolution in Killip class > I (25.4% vs. 17.0%, p<0.001), a higher median BNP elevation (315 [126–623] vs. 166 [64–431], p<0.001); and a lower average ejection fraction upon discharge (49.0±12 vs. 51±12, p=0.011). Patients on prior regular intake of ASA also had a higher prevalence of multivessel disease (38.4% vs. 28.9%, p<0.001) and multiple significant stenosis (70.2% vs. 61.7%, p<0.001). There was no significant difference regarding the percentage of electrical complications (2.3% vs. 1.2%, p=0.06), use of intra-aortic balloon pump (1.0 vs. 0.9%, p=0.74) and in-hospital death (3.0% vs. 2.4%, p=0.46). In a logistic regression model adjusted for age, sex, comorbidities and previous medication as variates, prior ASA intake was an independent predictor of a lower rate of AMI with ST-segment elevation (ExpB −0.34; 95% CI: 0.57–0.89; p=0.003). On the contrary, when adjusted to these variables, prior ASA intake was not an independent predictor of higher BNP (p=0.13) or higher probability of multivessel disease (p=0.22) or presence of ≥1 significant stenosis (p=0.31).

Conclusions

In this population of diabetic patients with a first episode of ACS, prior use of ASA in the context of primary prevention was associated with a significant lower rate of ST-segment elevation myocardial infarction.

Funding Acknowledgement

Type of funding source: None
Clinical implication of symptom for long-term outcomes after elective percutaneous coronary intervention
Authors: Ryota K , Wakabayasi K , Shibata K , Nishikura T , Shinke T , Tanno K
Published: November 2020

Background

The appropriate treatment for silent myocardial ischemia (SMI) is controversial. The prognosis of asymptomatic patients after percutaneous coronary intervention (PCI) is unknown. Asymptomatic patients might be sicker and have delay of diagnosis when they have coronary events in clinical course. We, thus, hypothesized SMI are associate with the poor outcomes after PCI for stable coronary artery disease (CAD).

Purpose

The present study compared the long-term outcomes of patients with SMI vs. stable angina pectoris (SAP) after elective PCI.

Methods

Our prospective registry database included 923 consecutive patients with CAD who underwent PCI from October 2015 to August 2018. Patients with emergent PCI, acute coronary syndrome at admission, or chronic total occlusion patients were not included. A total 613 patients (71.4±11.2 years, 75.7% male) who underwent elective PCI were studied. The end points included all-cause mortality, non-fatal myocardial infarction, and repeat revascularization.

Results

They were divided into 2 groups according to symptom status: SMI (n=392) and SAP (n=221). SMI patients were predominantly men, and more frequently had diabetes mellitus (197 [50.4%] vs. 91 [41.2%], p=0.028), previous myocardial infarction (44 [11.3%] vs. 8 [3.6%], p=0.001) and heart failure hospitalization.Echocardiography showed SMI groups had reduced ejection fraction (56.9±12.6 vs 63.3±9.1, P<0.001), extended left ventricular internal dimension in diastole (48.5±6.2 vs 47.4±5.8, p=0.048) and left ventricular diameter at end systole (32.8±7.6 vs 30.5±7.5, p=0.001). Mean duration of follow-up was 20.9±10.6 months. The incidence of non-fatal myocardial infarction and repeat revascularization was similar between the 2 groups (10 [2.6%] vs. 5 [2.3%], p=0.82, and 50 [12.8%] vs. 30 [13.6%], p=0.77, respectively). The incidence of all-cause and cardiovascular mortality was more frequent in SMI patients (26 [6.6%] vs. 6 [2.7%], p=0.036, and 9 [3.1%] vs 1 [0.5%], p=0.035, respectively). Kaplan-Meier survival curves indicated that SMI patients had significantly higher all cause-mortality than SAP patients (log-rank, p=0.0184, Hazard ratio 1.24 (1.05–1.47), p=0.013). In multivariable analysis, SMI was an independent predictor of all cause-mortality (Hazard-ratio 5.17, 95% CI 1.35–34.29, p=0.014).

Conclusion

In patients with stable CAD undergoing elective PCI, SMI was associated with an increase in mortality. Optimal care for SMI patients after PCI should be clarified in future studies.

Funding Acknowledgement

Type of funding source: None
Endothelial function and 6-year outcomes following an acute coronary syndrome in patients with a history or presence of cancer
Authors: Matsuzawa Y , Yoshii T.Y , Sato R.S , Nakahashi H.N , Akiyama E.A , Konishi M.K , Okada K.O , Maejima N.M , Iwahashi N.I , Ebina T.E , Hibi K.H , Kosuge M.K , Tamura K.T , Kimura K.K
Published: November 2020

Background

It has been reported that in the primary prevention settings, patients with cancer are exposed to an increased risk of cardiovascular disease through multiple mechanisms. However, among patients with established coronary artery disease, it is unknown whether cancer is an additional risk for endothelial dysfunction, mortality, and subsequent cardiovascular events.

Purpose

To determine endothelial function, mortality and cardiovascular events following acute coronary syndrome according to history/presence of cancer on (ACS).

Methods

Patients who were admitted to our university medical center for ACS were enrolled, and were divided according to the history/presence of cancer. We measured reactive hyperemia index before discharge in all patients to evaluate endothelial function. The logarithmic value of RHI (LnRHI) was used in the analyses. All patients were followed for cardiovascular death, non-cardiovascular death, myocardial infarction (MI), and stroke.

Results

Six-hundred and ninety patients with ACS were enrolled (mean age [SD] was 66 [12] years, male was 78%), and 73 patients (10.6%) had a history or presence of cancer. Endothelial function was not significantly different between ACS patients with and without the history/presence of cancer (LnRHI 0.64 (0.26) versus 0.59 (0.26), p=0.10). During the follow up period (the median 6.1 years), cardiovascular death occurred in 48 patients, non-cardiovascular death in 36, MI in 46, and Stroke in 31, respectively. The composite outcomes with all cause death, MI, and stroke occurred more frequently in the patients with the history/presence of cancer than those without (Figure A). However, the risk for cardiovascular death, MI, and stroke was similar between the two groups, and only non-cardiovascular mortality was significantly higher in the patients with the history/presence of cancer than those without (Figure B and C).

Conclusion

Among patients with ACS, the history/presence of cancer is associated with the risk of non-cardiovascular death, but not the risk for endothelial dysfunction and subsequent cardiovascular events.

Figure 1

Funding Acknowledgement

Type of funding source: None
Multi-vessel disease percutaneous coronary intervention versus coronary artery bypass grafting in patients with chronic kidney disease
Authors: Hassan Abdelnabi M , Almaghraby A , El-Amrawy A
Published: November 2020

Introduction

Coronary revascularization is associated with better prognosis in multivessel coronary artery disease (MV-CAD) chronic kidney disease (CKD) patients. However, whether coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is better remains unknown.

Aim of the study

To compare outcome of multi-vessel PCI versus CABG in the group of patients with CKD regarding in-hospital and one-year major adverse cardiovascular and cerebrovascular events (MACCE).

Methods

A retrospective analysis of the data of patients with established CKD with eGFR less than 60 ml/min with MV-CAD who underwent PCI or CABG were compared as regards in-hospital and one-year MACCE.

Results

A total number of 565 patients were reviewed, 230 patients had PCI while 335 patients had CABG. Comparing both groups regarding in-hospital MACCE, patients who had mutli-vessel PCI had significantly lower in-hospital death, cerebrovascular events and total MACCE than patients who had CABG (P-value = 0.03, 0.01, 0.04 respectively). While comparing both groups regarding 1-year MACCE, patients who had mutli-vessel PCI had significantly lower cerebrovascular events and total MACCE than patients who had CABG (P-value = 0.02, 0.03 respectively).

Conclusion

On the contrary to previously published data, in a retrospective study to determine which is better in CKD MV-CAD patients, Multi-vessel PCI for CKD patients and MVCAD had advantages over CABG as regards in-hospital and 1-year cerebrovascular accidents (stroke/TIA) and total MACCE. Large randomized controlled trials are needed to confirm our findings.

Funding Acknowledgement

Type of funding source: None
Apixaban versus Warfarin in Patients with Left Ventricular (LV) Thrombus, a prospective randomized trial
Authors: Alcalai R , Rashad R , Butnaru A , Moravsky G , Leibowitz D
Published: November 2020

Background

Patients with acute myocardial infarction (MI) have an elevated risk of stroke, mostly due to left ventricular (LV) thrombus formation, which typically occur within the first 2 weeks following an anterior MI. Currently the recommended management of LV thrombus after acute MI is anticoagulation with vitamin K antagonist. To date, there are no prospective data on the use of direct oral anticoagulants (DOACS) for stroke prevention in the setting of LV thrombus.

Aim

To assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI.

Methods

The study is a prospective, randomized, multi-center open label trial comparing apixaban (at a dose of 5 mg twice daily) with s.c enoxaparin 1mg/kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months in patients with LV thrombus detected by echocardiography 3 to 14 days after acute MI. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation as assessed by 2D echocardiogram. Secondary outcomes were stroke or systemic embolism, major bleeding and death from any cause.

Results

25 patients have been enrolled to date in 3 medical centers, 13 were randomized to apixaban and 12 to warfarin. Mean age was 59.8±10.7 and 19 (76%) were males with no difference between the study groups. Mean LV thrombus size at enrollment was 24X15 mm in the apixaban group and 19X14 in the warfarin group (p=NS). After 3 months of treatment thrombus completely resolved in all patients in the warfarin group and in 12 of 13 in the apixaban group. In one patient in the apixaban group who had a very large thrombus of 40x20mm size upon enrollment the thrombus size was reduced significantly to 20x12 after 3 months. No death, stroke or systemic embolism was documented in either group. There were two patients with major bleeding in the warfarin group, one had sub-arachnoid hemorrhage after 2 months and anticoagulation was stopped, and another had GI bleeding after 1 month and was switched to enoxaparin. One patient in the warfarin group refused to continue the treatment after 3 weeks. No major bleeding events were recorded in the apixaban group and all patients completed 3 months of treatment.

Conclusions

Our preliminary results indicate that apixaban is a safe and effective treatment for patients with LV thrombus post anterior wall MI.

Funding Acknowledgement

Type of funding source: None
Epigenetic interaction of miRNA-26a and P2Y12 gene DNA methylation on platelet reactivity under clopidogrel and their impact to the coronary flow after primary PCI in STEMI
Authors: Syam H , Sukmawan R , Dharma S , Alaztha G , Giyantini A , Prakoso R , Rudiktyo E , Zamroni D , Rejeki V.G , Juzar D.A , Rahardjo S.B , Adriantoro H , Santoso A
Published: November 2020

Background

Epigenetic factors such as miRNA-26A and P2Y12 DNA methylation play role in pathophysiology of cardiovascular disease. Clopidogrel-resistance is associated with worse cardiovascular outcome. The interactions between the expression of platelet miRNA-26a and P2Y12 DNA methylation to clopidogrel resistance and post procedural TIMI flow in STEMI patients undergoing primary PCI is unclear.

Purpose

To define interaction of epigenetic factors micro-RNA (miRNA)-26a expression and P2Y12 gene DNA methylation to the platelet reactivity under clopidogrel therapy, and their impact on the coronary flow after Primary PCI in patients with STEMI.

Methods

We studied STEMI patients who underwent primary PCI, receiving 600 mg loading dose of clopidogrel. Platelet reactivity assessed by VerifyNow P2Y12. Realtime PCR was performed to measure the expression of platelet miR-26a and DNA methylation of P2Y12 gene. Postprocedural epicardial coronary flow was assessed semi quantitatively.

Results

There were 100 patients were recruited. Among them, 59% have high miRNA-26a platelet expression, 60% had no methylation in their P2Y12 gene, and 27% had high platelet reactivity index under clopidogrel therapy. There was association between high miR-26a expression and reduced platelet inhibition under clopidogrel (OR 4.2, p<0.01), but not with DNA methylation of P2Y12 gene. High platelet reactivity index under clopidogrel therapy was associated with suboptimal coronary flow after primary PCI in STEMI patients (OR 3.3, p<0.05).

Conclusions

High miRNA-26a platelet expression, but not DNA methylation of P2Y12 gene, in patients with acute STEMI have significant association with high platelet reactivity under clopidogrel therapy. Furthermore, high platelet reactivity under clopidogrel is associated with suboptimal coronary flow in STEMI patients undergoing primary PCI.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Harapan Kita Honor Research Grant
Long-term differences in clot formation and endothelial function between STEMI patients with occlusion of infarct-related artery and those with spontaneous reperfusion
Authors: Kalinskaya A , Dukhin O , Uzhakhova K.H , Shpektor A , Vasilieva E
Published: November 2020

Introduction

Enhanced activation of endogenous fibrinolysis in ST-elevation myocardial infarction (STEMI) patients is the main cause of spontaneous reperfusion of the infarct-related artery (IRA) in the acute period. Whether this enhanced activation remains in the deferred period of myocardial infarction remains unclear.

Purpose

The main purpose of our work was to analyze the process of clot formation and endogenous fibrinolysis in patients with a history of myocardial infarction.

Methods

We included 51 patients with a history of myocardial infarction (median, 35 months). Of these patients, 19 had a spontaneous reperfusion of the IRA (SR group) during the index event, and 32 had a total occlusion of the IRA (occlusion group). We assessed parameters of clot formation and endogenous fibrinolysis using thromboelastometry and a thrombodynamics assay. We analyzed endothelial function using the flow-mediated dilation test (FMD).

Results

The process of clot formation was more active in the occlusion group than in the SR group. Thus, the initial, mean, and total clot velocity times were significantly higher in the occlusion group than in the SR group: 57.2 mcm/min vs. 60.25 mcm/min; 28,1 mcm/min vs. 31.9 mcm/min; and 28.7 mcm/min vs. 31.9 mcm/min, respectively; p<0.01. The clot size was much bigger in the occlusion group than in the SR group (1,190.5 mcm vs. 1,315 mcm; p<0.01). No differences in endogenous fibrinolysis parameters were observed between the two groups. Endothelium function was better in the SR-group than in the occlusion group (FMD 17.4% vs 11.3%, p<0.01).

Conclusion

STEMI patients with occlusion of the IRA and those with spontaneous reperfusion remain different in clot formation and endothelial function even after many years.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Russian Science Foundation grant
Coronary plaque instability is associated with inflammatory activity of visceral adipose tissue and carotid artery: a prospective pilot F-18 FDG PET/CT study
Authors: Pahk K , Kwon H.W , Eo J.S , Seo H.S , Kim S
Published: November 2020

Background

Dysfunctional Visceral adipose tissue (VAT) secretes pro-inflammatory cytokines and promotes inflammatory cell infiltration into VAT thereby boosting insulin resistance and systemic inflammation which eventually lead to increased risk of cardiovascular disease (CVD). F-18 FDG PET/CT is well known to reflect the inflammatory activity of classically activated (M1) macrophage.

Purpose

We hypothesized that F-18 FDG PET/CT could reflect the inflammatory activity of dysfunctional VAT and carotid artery which were associated with coronary plaque instability.

Methods

A total of 90 participants were enrolled in this prospective study. F-18 FDG PET/CT was performed in 32 participants with acute myocardial infarction (AMI) within a week of disease onset, 33 participants with stable coronary artery disease (CAD), and 25 control subjects. Maximum standardized uptake value (SUVmax) was calculated in VAT, subcutaneous adipose tissue (SAT), spleen, and bone marrow (BM). Target-to-background ratio (TBR) was calculated in right carotid artery and right jugular vein.

Results

The SUVmax of VAT and the TBR of right carotid artery were highest in patients with AMI, intermediate in patient with stable CAD, and lowest in control subjects. Systemic inflammation surrogate markers such as high-sensitivity C-reactive protein, spleen SUVmax were also showed similar pattern like the SUVmax of VAT and the TBR of right carotid artery. Furthermore, multiple linear regression analysis showed that the SUVmax of VAT and spleen SUVmax were independently associated with the TBR of right carotid artery.

Conclusions

F-18 FDG PET/CT could reflect the synchronized systemic inflammation in VAT and carotid artery which could affect the coronary artery instability. Furthermore, our findings offer clinical insights into risk stratification, monitoring of therapy, and physiological changes in the development of CAD.

Funding Acknowledgement

Type of funding source: None
Low-dose colchicine in patients treated with percutaneous coronary interventions for myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT)
Authors: L'Allier P.L , Tardif J.C , Kouz S , Waters D.D , Diaz R , Maggioni A.P , Pinto F.J , Gamra H , Kiwan G.S , Berry C , Lopez-Sendon J.C , Koenig W , Blondeau L , Guertin M.C , Roubille F
Published: November 2020

Background/Introduction

Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent anti-inflammatory medication that was shown to significantly lower the risk of ischemic cardiovascular events compared to placebo among subjects with a recent myocardial infarction (MI) in the main COLCOT trial. Patients treated with percutaneous coronary intervention (PCI) after MI represent an important subpopulation that may derive particularly important benefits from colchicine.

Purpose

To assess the impact of low-dose colchicine on cardiovascular events in subjects treated with PCI for an index MI.

Methods

We performed an international, randomized, double-blind trial involving patients recruited within 30 days after a MI (main COLCOT trial; n=4745). In this trial, patients were eligible if they had a confirmed myocardial infarction within 30 days before enrollment, had completed any planned percutaneous revascularization procedures and were treated medically according to national guidelines that included the intensive use of statins. Subjects were randomly assigned to receive oral colchicine 0.5 mg once daily or matching placebo. Among the entire COLCOT study population, 4408 subjects were treated with PCI for the index MI and form the COLCOT-PCI study population. We analyzed the time to the first positively adjudicated event of the composite of CV death, resuscitated cardiac arrest, acute MI, stroke or urgent hospitalization for angina requiring coronary revascularization (primary endpoint).

Results

In the main COLCOT trial, low-dose colchicine led to a significantly lower risk of the primary endpoint (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; p=0.02). In the COLCOT-PCI subpopulation, low-dose colchicine was associated with a large reduction in the risk of a primary endpoint event (hazard ratio, 0.72; 95% confidence interval [CI], 0.57 to 0.92; p=0.008). The hazard ratios for individual components of the composite primary endpoint were 0.71 (95% CI, 0.37 to 1.33) for death from cardiovascular causes, 0.84 (95% CI, 0.26 to 2.75) for resuscitated cardiac arrest, 0.90 (95% CI, 0.66 to 1.21) for myocardial infarction, 0.25 (95% CI, 0.08 to 0.76) for stroke, and 0.42 (95% CI, 0.25 to 0.71) for urgent hospitalization for angina requiring coronary revascularization.

Conclusion

Low-dose colchicine markedly reduces the risk of ischemic cardiovascular events in patients treated with PCI for their index MI.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Government of Quebec and Canadian Institutes of Health Research
Gut microbiota profile of patients with acute coronary syndrome, effect of the most frequent comorbidities
Authors: Martin De Miguel I , Fernandez A.I , Lozano N , Gutierrez-Ibanes E , Sanz Ruiz R , Diez-Delhoyo F , Vazquez S , Reigadas E , Garcia De Viedma D , Elizaga Corrales J , Fernandez-Aviles F.J , Bermejo J
Published: November 2020

Introduction

Gut microbiota dysbiosis may modify the inflammatory state, which could trigger the development of acute coronary syndrome (ACS). Moreover, cardiovascular risk factors may alter the microbiota profile involved in ACS development.

Purpose

To address the potential role of alterations in microbiota as triggers of ACS and their cardiovascular comorbidities in patients with ACS.

Methods

Patients admitted for ACS were prospectively included. Stool samples were collected in the first 24 hours after admission. For microbiota analysis, Operational Taxonomic Unit (OTUs) method from V4 amplicon of 16S rRNA was employed. Identification, quantification, clusterization and taxonomic classification of OTUs was performed in Mothur through RDP database. ACS patient microbiota was compared with the microbiota of 10 healthy controls. The microbiota changes analyses were evaluated with ANOVA analysis.

Results

41 ACS patients with a mean age of 62±11 years old were included. 34 (83%) were males, 17 (42%) suffered arterial hypertension, 18 (44%) dyslipidaemia, 37 (90%) diabetes mellitus and 16 (39%) were current smokers. A multidimensional scaling model allowed us to clearly delineate different clusters between patients with ACS and healthy controls. This was due to important differences in the main phylum of the human microbiota (Table) Bacteroidetes, Firmicutes / Bacteroidetes ratio and Actinobacteria. In addition, there was a significant decrease in protective Cyanobacteria (p=0.03) and Proteobacteria (p=0.04) in men. Hypertensive and dyslipidaemic patients had a significantly higher amount of Firmicutes, Clostridia (p=0.05) and Erysipelotrichia (p=0.03) classes, respectively. Patients with diabetes had significantly less protective Proteobacteria (p=0.002) and Spirochaetes (p=0.04). Finally, smoking was associated with a significant increase in pathogenic Lentisphaerae (p=0.04).

Conclusions

Patients with ACS have clear pathogenic alterations of their gut microbiota. Classical cardiovascular risk factors induce different patterns of gut dysbiosis.

Gut microbiota profile.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Carlos III Health Institute
Pericoronary adipose tissue attenuation (PCAT) is associated with high-risk atherosclerotic plaque and subsequent acute coronary syndrome in patients with stable coronary artery disease
Authors: Yuvaraj J , Lin A , Nerlekar N , Munnur R.K , Cameron J , Nicholls S.J , Wong D.T.L
Published: November 2020

Background

High-risk plaque (HRP) features detected on computed tomography coronary angiography (CTCA) are associated with subsequent development of acute coronary syndrome (ACS). Pericoronary adipose tissue attenuation (PCAT) is a novel CT-derived non-invasive marker of coronary inflammation. The association between PCAT, HRP and outcomes is unknown.

Purpose

To evaluate the association between high-risk plaque HRP characteristics, ACS and PCAT attenuation as a surrogate marker of coronary inflammation.

Methods

Patients with stable chest pain referred for CTCA between 2011 and 2013 with outcome data were included. Patients with HRP were propensity matched to patients without HRP. PCAT-RCA and PCAT-lesion were assessed using semi-automated software (AutoPlaque version 2.0). PCAT-RCA was measured around the proximal 10–50 mm of the right coronary artery (RCA). PCAT-lesion was measured around the HRP or lesion with highest-grade stenosis in patients without HRP.

Results

78 patients (67±10 years, 67% males) included 41 (52.6%) patients with HRP. Median PCAT-RCA was higher in HRP patients than non-HRP patients (−80.4 HU [IQR −86.1, −76.5] vs. −86.3 HU [IQR −92.2, −77.0], p=0.02). PCAT-Lesion was not significantly different between HRP and non-HRP patients (−78.7 HU [IQR −84.4, −73.4] vs. −82.8 HU [IQR −91.1, −75.4], p=0.16). More patients with HRP developed a subsequent ACS (24.4% vs. 5.4%, p=0.008). HRP patients who experienced an ACS demonstrated a higher PCAT-RCA (−76.6 HU [IQR −81.3, −72.4] vs. −82.6 HU [IQR −87.4, −78.0], p=0.018) and PCAT-lesion (−74.3 HU [IQR −77.1, −68.4] vs. −80.7 HU [IQR −84.8, −74.9], p=0.04) compared to those who did not experience an ACS.

Conclusion

PCAT attenuation is elevated in stable CAD patients with HRP features. Measures of periarterial inflammation were also more evident in HRP patients who develop ACS, indicating a potential contribution to vulnerability. The implications for integration of these measures in clinical practice require further investigation.

Funding Acknowledgement

Type of funding source: None
Sex-related differences in geometry, plaques and shear stress related plaque-progression in human coronary arteries
Authors: Wentzel J.J , Papafaklis M , Antoniadis A , Takahashi S , Cefalo N.V , Cormier M , Saito S , Coskun A , Stone P.H
Published: November 2020

Background

Atherosclerosis manifests itself differently in women compared to men. Since the pathophysiology of atherosclerotic plaques is known to be related to endothelial shear stress (ESS), it was hypothesized that female compared to male coronary arteries demonstrate a different i) ESS and ii) ESS related plaque progression.

Methods

1183 coronary arteries (male/female:944/239) from the PREDICTION trial were studied for differences in vessel geometry (plaque area (PA) and lumen area (LA)), hemodynamic parameters (flow, minimal ESS over 90 degree arc (minESS) and maximal ESS over 90 degree arc (maxESS)) and ESS related plaque progression (1 year follow up) measured as change in maximal plaque thickness and plaque burden comparing female to male arteries. Arterial geometry and ESS measures were derived from IVUS-based vascular profiling and reported per 3 mm segments. For plaque progression studies minESS was subdivided into low, mid and high (<1,1–1.7,>1.7 Pa). To test statistical differences univariate anova or linear mixed models were used.

Results

13030 3mm-segments (m/f: 10.465/2565) were analyzed. Female compared to male coronary arteries were smaller and presented with less plaque area (Table I). No differences in average ESS, minESS and maxESS were found for male versus female coronary arteries, partly explained by the lower flows in female arteries (Table I). The ESS-related plaque growth showed for both sexes an significant inverse relationship between maximal wall thickness (Figure, left) and plaque burden (Figure, right) and the three minESS categories. However, ESS-related plaque growth was not different for male vs females.

Conclusion

Our data demonstrated that vessel and plaque size are smaller in female compared to male coronary arteries. However, ESS and ESS related plaque progression were not different.

Shear stress related plaque progression

Funding Acknowledgement

Type of funding source: None
East Asian variant aldehyde dehydrogenase Type 2 genotype exacerbates myocardial ischemia/reperfusion injury in men among patients with ST-segment elevation myocardial infarction -sex differences-
Authors: Ishida T , Arima Y , Mizuno Y , Harada E , Yasue H , Tsujita K
Published: November 2020

Background

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes including those generated during ischemia/reperfusion (I/R) injury in acute myocardial infarction. The deficient variant ALDH2 genotype (ALDH2*2) is prevalent among East Asians. We examined whether ALDH2*2 exacerbates I/R injury in Japanese patients with acute ST-segment elevation myocardial infarction (STEMI) utilizing Mendelian randomization.

Methods and results

The study subjects comprised 248 Japanese patients with STEMI (187 men and 61 women, mean age 67.1±11.5) who underwent successful primary percutaneous coronary intervention. Of these patients, 129 (52.0%) were the carriers of ALDH2*2 and 119 (48.0%) those of wild ALDH2*1/*1 on genotyping by direct application of the TaqMan polymerase chain system. There were no differences in clinical characteristics between the ALDH2*2 and ALDH2*1/*1 group except lower alcohol habit in the ALDH2*2 group. However, the peak plasma levels of creatine phosphokinase myocardial binding (CKMB), a marker of myocardial injury, were significantly higher (a median 234.0 vs 150.0 U/L, P<0.001 in the ALDH2*2 group. Furthermore, the peak CKMB levels were higher in ALDH2*2 group in men (a median 2 75.0 vs 144.9 U/L, P<0.001) but not in women (P=0.855) and there was a significant interaction between sex and ALDH2*2 on I/R injury (χ2=8.362, P=0.004).

Conclusions

The peak plasma levels of CKMB were higher in STEMI patients with ALDH2*2 than in those with ALDH2*1/*1 among men but not women. These findings identified deficient ALDH2 activity to be targeted for treatment of STEMI specifically in men with ALDH2*2.

Visual overview

Funding Acknowledgement

Type of funding source: None
Impact of epicardial adipose tissue increase after ST elevation Myocardial Infarction (STEMI) on IL-13 and left ventricular remodelling
Authors: Parisi V , Cabaro S , D'Esposito V , Petraglia L , Conte M , Gerundo G , Campana P , Caruso A , Grimaldi M.G , Pilato E , Comentale G , Leosco D
Published: November 2020

Background

The role of epicardial adipose tissue (EAT) in myocardial diseases is well established, and several evidence suggest that EAT may negatively affect left ventricular (LV) remodelling through an imbalanced production and secretion of pro and anti-inflammatory cytokines. Of these, the IL-13 it is known to play a positive activity on cardiac remodelling. Nowadays, the crosstalk between EAT and the myocardium is still poorly understood and the effects of myocardial ischemia on morphological and functional properties of EAT are almost unknown.

Purpose

In the present study we explored whether an increase of EAT thickness after STEMI might be associated with unfavourable LV remodelling at 3 months (T1). We also evaluated the relationship between changes (Δ) of EAT thickness and systemic levels of Interleukin (IL)-13 which is known to play a favourable activity on LV remodelling after STEMI.

Methods

We enrolled 66 patients with first STEMI, undergoing primary percutaneous angioplasty. At baseline and at 3 months we performed a complete echocardiogram, including EAT maximal thickness assessment, and determined circulating levels of IL-13.

Results

At 3 months after STEMI, the population was stratified into two groups according to different EAT remodelling after cardiac event: Group 1, patients with an increased EAT thickness (Δ EAT>1; 30 patients) and Group 2, patients with unchanged or decreased EAT thickness (Δ EAT<1). The two groups did not differ for age, gender and atherosclerotic risk factors. Group 1 had a worse LV remodelling at 3 months with higher LV diastolic and systolic volumes, lower LV ejection fraction (p=0.003; p=0.013; p=0.013 respectively) and worse diastolic function (E/e'; p=0.011). Of interest, EAT thickness increase was paralleled by circulating IL-13 reduction (p=0.022).

Conclusion

Myocardial injury can result in EAT increase which is associated to worse LV remodelling probably through the loss of the protective role of IL-13.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This research has been funded by the University of Naples “Federico II” and “Compagnia di San Paolo e l'Istituto Banco di Napoli” within the competitive grant STAR 2018; Valentina Parisi is the principal investigator
A real world analysis of NSTE-ACS in more than 4000 patients: accuracy of GRACE and TIMI scores in mortality prediction
Authors: Borges-Rosa J , Ferreira J , Oliveira-Santos M , Monteiro S , Goncalves F , Monteiro P , Baptista R , Goncalves L
Published: November 2020

Introduction

The TIMI (Thrombolysis in Myocardial Infarction) and GRACE (Global Registry of Acute Coronary Events) risk scores identify high-risk patients with Non-ST elevation acute coronary syndrome (NSTE-ACS) who can benefit from an early invasive strategy.

Purpose

We aimed to compare both scores predictive accuracy for mortality in a real-world cohort of patients presenting with NSTE-ACS.

Methods

We retrospectively evaluated 4264 patients admitted to our coronary intensive care unit between 2004 and 2017 with a diagnosis of NSTE-ACS. The TIMI and GRACE scores were calculated for each patient, and all-cause mortality was recorded during hospitalization, at one month and one year. To better characterize global troponin release, we defined Total Troponin (TT) as the sum of initial and discharge troponin. We used the area under the receiver operating characteristic curve (AUC) to compare the predictive value of both scores for mortality during hospitalization, at one month and one year.

Results

Mean patient age was 67.6±12.4 years and 66.4% were male (n=2833). Mean GRACE score was 124.6±35.8 and mean TIMI score was 2.7±1.6. There was a weak correlation between GRACE and TIMI score (r=0.3, p<0.001). In-hospital mortality was 2.8%: the GRACE score showed higher AUC (0.845, 95% CI 0.805–0.804, p<0.001) compared to TIMI (0.581, 95% CI 0.519–0.643, p=0.009) (Figure 1). Mortality at one month was 5.1%: the GRACE score showed higher AUC (0.842, 95% CI 0.814–0.869, p<0.001) compared to TIMI (0.586, 95% CI 0.541–0.630, p<0.001). Mortality at one year was 11.4%: the GRACE score showed higher AUC (0.811, 95% CI 0.789–0.822, p<0.001) compared to TIMI (0.591, 95% CI 0.560–0.622, p<0.001) (Fig. 1). Analyzing Unstable Angina and Non-ST segment elevation myocardial infarction separately, the GRACE score also showed higher AUC compared to TIMI. Exploratory analyses revealed a combined indicator (GRACE score + TT) which had higher AUC (0.876, 95% CI 0.844–0.907, p<0.001) compared to GRACE score (0.855, 95% CI 0.823–0.887, p<0.001) for one month mortality and for one year mortality (0.818, 95% CI 0.792–0.844, p<0.001 vs. 0.813, 95% CI 0.788–0.839, p<0.001).

Conclusion

In patients with NSTE-ACS, GRACE risk score is a better predictor of in-hospital, one month and one-year mortality, compared to TIMI risk score. TT, as a measure of ischemia burden, might improve accuracy of GRACE score in predicting short and long-term mortality.

Figure 1

Funding Acknowledgement

Type of funding source: None