bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfusion requirements in cardiac Surgery III (TRICS III), Ticagrelor Substudy
Authors: Alraddadi H , Belley-Cote E , Shehata N , Mazer D , Whitlock R.P
Published: November 2020

Background

Ticagrelor, in addition to aspirin, has been demonstrated to reduce morbidity and mortality in patients with acute coronary syndrome compared to clopidogrel with aspirin. The treatment effect appeared to be maintained in the subgroup of patients who underwent urgent surgical revascularization. However, the risk of postoperative bleeding in these patients has not been well described.

Research question

We aimed to establish the effect of ticagrelor exposure within 7 days before surgery on blood loss as measured by postoperative chest tube output and blood product use.

Method

In a nested cohort study of patients enrolled in the Transfusion Requirements in Cardiac Surgery III (TRICS III) trial, we compared chest tube output and blood product use in patients based on their preoperative exposure to ticagrelor ≤3 days versus >3 days before surgery.

Results

Of the 5243 patients in TRICS III, 87 patients were exposed to ticagrelor within 7 days with a mean age of 78 years (SD 6) and 74% were male. Patients exposed to ticagrelor 3 days or less before surgery bled a median of 730 ml (IQR 295, 2195) postoperatively in the first 24 hours postoperatively, compared to 518 ml (IQR 350, 1000) for those for whom ticagrelor was held for more than 3 days. We log-transformed the data and found that recent ticagrelor exposure (≤3 days) was associated with significantly more blood loss compared to no exposure for more than 3 days (P-value: 0.01).

69.6% of patients in the recent exposure group received at least one red blood cell transfusion versus 54.7% in patients exposed to ticagrelor more than 3 days pre-operatively (p-value: 0.214). Platelet and fresh frozen plasma transfusion were 52.2% vs 15.6% (p-value 0.001), and 39.1% vs 9.4% (p-value 0.003), respectively, for ticagrelor exposure ≤3 days compared to >3 days.

Cryoprecipitate use was 17.4% in the ≤3 days group and 3.1% in the >3 days group (p-value 0.04). Only 1 patient in each group received prothrombin complex concentrate (PCC) transfusion. And 1 patient with exposure ≤3 days received Factor VII.

Conclusion

Exposure to ticagrelor within 3 days of surgery is associated with an increased risk of postoperative bleeding as assessed by greater chest tube output at 24 hours and more patients requiring blood product transfusion. A ticagrelor-reversing agent may improve the outcomes of patients who have been recently exposed to ticagrelor and require urgent cardiac surgery.

Funding Acknowledgement

Type of funding source: None
Heparins crossover in percutaneous coronary intervention: is it a real issue in real-world practice?
Authors: Li Y , Weng H.Y , Zhang L , Jiang J , Zhang Y , Li J.P
Published: November 2020

Background/Introduction

Current guidelines do not recommend heparins crossover in percutaneous coronary intervention (PCI) between unfractionated heparin (UFH) and low molecular weight heparin (LMWH), which is only based on the post-randomization crossovers analysis of SYNERGY trial. However, in real-world practice, heparins crossover is common.

Purpose

To evaluate bleeding complications in patients who underwent PCI using periprocedural crossover of heparin therapy.

Methods

From January 2015 to December 2019, all consecutive patients who underwent PCI in our hospital were retrospectively enrolled in this analysis. The primary outcome was a hemoglobin drop ≥3g/dl within 72 hours after the procedure.

Results

A total of 5,001 patients, including 4,487 (89.72%) with heparins crossover. As shown in figure 1, after a 1:4 ratio of propensity score matching of age, gender, prior medical history, vital signs, body mass index, puncture site, coronary lesion number, stent number, baseline hemoglobin and platelet counts, 539 with crossover and 165 without were matched. There was no difference of the incident of bleeding (1.67% vs. 0.61%, P=0.562) and thrombocytopenia (1.86% vs. 1.82%, P=0.562) between the two groups. In multivariate adjusted logistic regression models, there was no significant association with heparins crossover and bleeding (odds ratio: 0.36; 95% CI, 0.05–2.85) or thrombocytopenia (odds ratio: 0.95; 95% CI, 0.26–3.53).

Conclusion(s)

In this real-world retrospective analysis of a single center, the periprocedural heparins crossover was not associated with increased bleeding or thrombocytopenia risk.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Youth clinical research project of Peking University First Hospital
Clinical features and prognosis of acute myocardial infarction due to coronary artery embolism
Authors: Hata R , Shimada T , Shima Y , Okabe K , Ohya M , Miura K , Murai R , Amano H , Kubo S , Tada T , Tanaka H , Fuku Y , Goto T , Kadota K
Published: November 2020

Background

Coronary artery embolism (CE) is one of the important causes of acute coronary syndrome (ACS). The feature of CE is that angiographic evidence of coronary artery embolism and thrombosis without atherosclerotic components. However, the prevalence of CE remains unknown because of the diffifulty to diagnose in the acute settings. A recent retrospective analysis suggested that up to 3% of ACS cases may result from CE.

Purpose

The aim of this study was to elucidate the prevalence, clinical features and long-term outcomes including all-cause and cardiac death.

Methods

We analysed the consecutive 2695 patients with first AMI performed coronary intervention between January 2004 and July 2017. CE was diagnosed by clinical histories and angiographic findings. We retrospectively evaluated the clinical and lesion characteristics and outcomes including all-cause and cardiac death.

Results

The prevalence of CE was 2.0% (n=55; CE group and n=2640; non-CE group), including 8 (15%) patients with multivessel CE. The CE group had higher average age (70.8±14.9 vs. 68.4±12.6, p<0.01), prevalence of female (54% vs. 27%, p<0.01), lower prevalence of smoking (34% vs. 62%, p<0.01). The common causes with CE were atrial fibrillation (47%), and malignant tumor (9%), and cardiomyopathy (5%), and patent foramen ovale (4%). Only 20% of patients with CE were treated with anti-coagulant therapy. The rate of distal infarction site (defined as #4, #8, #14–15) was significantly higher in CE group than non-CE group (54.0% vs. 4.9%, p<0.01). During median follow-up of 53.6 [32.6–77.3] months, CE and thromboembolism recurred in 5 patients (CE: 1 patient, stroke 4 patients). The 4-year incidence of all-cause death was significantly higher in the CE group, but cardiac death was not significantly different between the groups (28.8% vs. 14.8%, p=0.03; 12.8% vs. 5.1%, p=0.11).

Conclusion

Compared with non-CE group, the prevalence of distal infarction site was significantly higher in the CE group, and the incidence of cardiac death is not significantly different.

Funding Acknowledgement

Type of funding source: None
Galectin-3 predicts cardiovascular events in patients with type-2 diabetes
Authors: Lorenzo-Almoros A , Pello A , Acena A , Martinez-Milla J , Tarin N , Cristobal C , Blanco-Colio L.M , Martin-Ventura J.L , Huelmos A , Gutierrez-Landaluce C , Lopez-Castillo M , Alonso J , Egido J , Lorenzo O , Tunon J
Published: November 2020

Introduction

Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population.

Methods

We followed 964 patients with coronary artery disease (CAD), assessing at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes.

Results

Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 patients had T2DM. Patients with T2DM showed higher MCP-1 [144 (113–195) vs. 133 (105–173) pg/ml, p=0.006] and galectin-3 [8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/ml, p=0.049] levels.

Median follow-up was 5.39 years (2.81- 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients [HR 1.57 (1.07–2.30); p=0.022], along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in non-diabetic patients [HR 1.21 (1.04–1.42); p=0.017 and HR 1.23 (1.05–1.44); p=0.012, respectively], along with male sex and age.

Galectin-3 was also the only biomarker that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events.

Conclusion

In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM.

Effect of Gal-3 on the primary endpoint

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III
Serum phosphate level and the outcome of coronary artery disease after coronary revascularization
Authors: Tsai T.Y , Lim S.S , Yang Y.L , Chan S.C , Hsu P.F , Wu C.H , Huang S.S , Lin S.J , Pan J.P , Lu T.M , Huang P.H , Leu H.B
Published: November 2020

Background

Elevated serum phosphate levels have been linked with increased risk of cardiovascular disease and mortality with conflicting results. However, whether phosphate level is associated with poor outcome for CAD patients after successful percutaneous coronary intervention (PCI) remained undetermined.

Purpose

We aimed to investigate the relationship between phosphate levels and the outcome of CAD patient undergoing PCI.

Methods

We enrolled 2894 patients (2220 male 71.59±12.20 y/o) with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from our hospital from 2006 to 2015. The baseline characteristics, biochemical data and procedure details were collected. Serum phosphorus levels were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure.

Results

During an average 65.06±32.1-month follow-up, there were 173 cardiovascular deaths, 211 nonfatal myocardial infarctions, 91 nonfatal strokes, 416 hospitalizations for heart failure, and 579 revascularization procedures. There was a J-curve like linear association between serum phosphorus and future adverse event. In the multivariate analysis adjusted with comorbidities including underlying renal function, subjects with increasing every 1 mg/dL in serum phosphorus level had a higher risk of MACE (HR: 1.13, 95% CI: 1.03–1.24), cardiovascular death (HR: 1.37,95% CI: 1.22–1.55), heart failure-related hospitalization (HR: 1.12, 95% CI: 1.02–1.23), and total major CV events (HR: 1.12, 95% CI: 1.05–1.21). (Figure)

Conclusion

Serum phosphate level is significantly associated with increased risk of adverse events in CAD patients after successful PCI even considering underlying renal function.

Figure 1

Funding Acknowledgement

Type of funding source: None
Coronary artery ectasia in acute myocardial infarction: to be culprit or not to be?
Authors: Maalemben Messaoud B , Maza M , Ratheau E , Debeaumarche H , Pommier T , Zeller M , Cottin Y
Published: November 2020

Background

Coronary artery ectasia (CAE), is only found in about 1% of acute myocardial infarction (AMI), but represents a clinical challenge in the setting of percutaneous coronary intervention (PCI), considering 1) culprit lesion or not, 2) a solely CAE or mixt 3) number, localization and size of CAE, 4) etiology and 5) therapeutic strategies. Only few studies from small cohorts have focused on infarct-related arteries. We aim to assess the impact of CAE as culprit artery on management strategy.

Methods

From 2010 to 2019, this study prospectively analyzed the characteristics, and management of 70 consecutive admitted for an AMI and with CAE at coronary angiography. Patients with ectatic infarcted-related artery (ERIA) were compared with patients without ectasia localized on infarcted-related (No ERIA).

Results

Among the 70 patients included, most had ERIA 47 (67%). ERIA patients had more frequently diabetes than patients without ERIA (32 vs 4%, p=0.01). The rate of other CV risk factors, and chronic medications, including antiplatelet agents and anticoagulants,.were similar for the 2 groups. Moreover, no difference was observed between the 2 groups for clinical parameters and biological data. Whatever the group, the ectatic artery is mainly located on the right coronary artery (RCA) (73%), of which most were ERIA (77%). ERIA group had less frequently anterior wall location STEMI (18 vs 65%, p= <0.001). The rate of diffuse coronary artery disease (91 vs 92%) and maximum CAE diameter (6.36 (6.00–7.00) mm vs 6.14 (5.53–7.64) mm, p=0.571) were similar for the 2 groups. SYNTAX was lower in ERIA patients (9.5 (2.0–18.0) vs 13.5 (7.0–23.0), p=0.031). A complete reperfusion was more frequently achieved in no ERIA group (70 vs 47%, p=0.073).

PCI data and hospital mortality are shown in Table.

Conclusion

CAE management is strongly dependent on the presence of CAE on IRA. Although rare, the optimal treatment strategy of patients with AMI and CAE remains to be elucidated. The place of intravascular ultrasound imaging needs to be investigated.

Funding Acknowledgement

Type of funding source: None
The change of serum serotonin levels between acute coronary syndrome and chronic stable angina undergoing percutaneous coronary intervention
Authors: Han D , Shin D.G , Kang M.K , Choi S , Lee N , Cho J.R
Published: November 2020

Background

Activated platelets release serotonin (5-hydroxytryptamine, 5HT) causing vasoconstriction and aggregation of platelets in patients with acute coronary syndrome (ACS). It can lead to undergo percutaneous coronary intervention (PCI). We investigated the serial changes of serotonin level in patients with ACS and chronic stable angina (CSA) treated with PCI.

Methods

From July 2009 to April 2010, 123 consecutive patients who have undergone PCI for either ACS (n=63) or CSA (n=60) were enrolled. After the loading dose of aspirin 300mg and clopidogrel 600mg before PCI, maintenance once daily dose of 100mg and 75mg have been given from the day after PCI in all patients. Serum serotonin level (SERO) were serially measured at baseline, pre-, post-PCI, 90 min, 6 hours, 12 hours, 24 hours and 48 hours to compare between ACS and CSA groups. All demographic, biochemical variables, and clinical events were also collected for comparison in each group.

Results

SERO at post-PCI (55.2±120.0 vs 20.1±24.0, p=0.03) and peak level (94.0±170.9 vs 38.8±72.3, p=0.02) were significantly higher in ACS group. SERO after 90 min (34.4±66.1 vs 28.7±38.2, p=0.8), 6 hours (23.9±38.3 vs 10.1±10.0, p=0.34), 24 hours (55.8±108.5 vs 37.2±88.2, p=0.39) and 48 hours (43.5±122.9 vs 25.2±65.5, p=0.53) tended to be higher in ACS group than CSA group without statistical significance. SERO rebounded at 24 hours post-PCI and dropped at 48 hours.

Conclusions

SERO was more elevated in patients with ACS than those with CSA undergoing PCI, suggesting the need for more potent and sustained platelet inhibition particularly in ACS patients. SERO might be considered as a substitute marker of platelet activation. Triple antiplatelet therapy including selective serotonin receptor antagonist on top of aspirin and clopidogrel could be as an option for ACS patients undergoing PCI

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Hallym University Research Fund 2017 (HURF-2017-84)
Impact of smoking habit on platelet reactivity in a cohort of patients admitted due to an acute coronary syndrome
Authors: Gomez Polo J.C , Vivas Balcones D , Marcano Fernandez A.L , Playan Escribano J , Lugo Gavidia L.M , Bernardo E , Ortega Pozzi M.A , De La Hera Galarza J.M , Tello Montoliu A , Besteiro Vazquez A , Silva I , Marin F , Roldan Rabadan I , Gomez Hospital J.A , Ferreiro J.L
Published: November 2020

Background

Several pharmacodynamic studies have shown the impact of smoking habit on platelet reactivity; with a reduction on platelet aggregation. Wether this inhibition in platelet reactivity is due to tobacco effects in platelet signaling pathways or due to a pharmacodynamic interaction with antiplatelet therapies is not well stablished.

Purpose

Our aim was to study the influence of smoking habit in platelet reactivity and in the response to P2Y12 inhibitors.

Methods

Patients admitted in four tertiary care hospitals due to an acute coronary syndrome that undergone percutaneous coronary intervention (PCI) were consecutively and prospectively recruited. All the patients received dual antiplatelet therapy with aspirin and a P2Y12 inhibitor following current European Guidelines. Platelet function was assessed at day 1 and day 30 post-PCI by VerifyNow P2Y12, VASP (Vasodilator-stimulated phosphoprotein) y MEA (Multiple electrode aggregometry).

Results

A total of 1000 patients were enrolled, of whom 12 had to be excluded due to inaccurate processing of blood samples. 372 patients (37,6%) had smoking habit. Non-smoking patients showed higher prevalence of high blood pressure [423 (68.7%) vs 196 (52.7%)] and diabetes mellitus [213 (34.6%) vs 81 (21.8%)]. Smoking patients were younger [57.3 (9,6) years old vs 68.4 (11.1)], with higher incidence of acute coronary syndrome with ST segment elevation [184 patients (49,5%) vs 241 (39.1%), p<0,001]. There were no differences in platelet function at day 1. When analysing platelet function 30 days post-PCI, a lower inhibition of platelet reactivity in non-smoking patients as compared with smoking patients was observed in those treated with clopidogrel, with higher prevalence of clopidogrel-resistance in non-smoking patients (VerifyNow, 51,2% prevalence of high platelet reactivity in non-smoking patients vs 34,9% 30 days after PCI, p=0,023). On the other hand, smoking patients that received ticagrelor did not show any differences. Patients with smoking habit treated with prasugrel showed a lower response of borderline statistical significance.

Conclusion

Smoking habit was associated with a lower response to prasugrel of borderline significance, and with higher response to clopidogrel, according with previous studies suggesting a pharmacodynamics interaction between tobacco use and P2Y12 inhibitors.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fondo de Investigaciones Sanitarias (FIS)
Influence of myocardial damage on serum procalcitonin in ST-elevation myocardial infarction
Authors: Reindl M , Tiller C , Holzknecht M , Lechner I , Henninger B , Mayr A , Brenner C , Klug G , Bauer A , Metzler B , Reinstadler S.J
Published: November 2020

Background

Myocardial tissue injury due to acute ST-elevation myocardial infarction (STEMI) initiates an inflammatory response with a release of systemic inflammatory biomarkers including C-reactive protein (CRP) and white blood cell count (WBCc), which, however, hampers the usefulness of these routine biomarkers to identify concomitant infections. The clinical role of Procalcitonin (PCT), a promising marker of bacterial infections, to detect concomitant infections in acute STEMI is unknown, mainly because it is unclear whether myocardial injury per se induces a systemic PCT release.

Purpose

To investigate release kinetics of serum PCT in the acute setting of STEMI and possible associations with myocardial injury markers as comprehensively assessed by cardiac magnetic resonance (CMR) imaging.

Methods

In this prospective observational study, we included 141 STEMI patients treated with primary percutaneous coronary intervention (PCI). Concentrations of PCT, high-sensitivity CRP (hs-CRP), WBCc and high-sensitivity cardiac troponin T (hs-cTnT) were measured serially at day 1 and day 2 after infarction. CMR imaging to assess infarct size (IS), extent of microvascular injury (MVI) and occurrence of intramyocardial haemorrhage (IMH) was performed within the first week following STEMI.

Results

Median concentrations of PCT were 0.07μg/l at both time points. In 140 patients (99%), both PCT values were within the normal range (≤0.5μg/l). Whereas hs-CRP, WBCc, and hs-TnT were significantly correlated with CMR markers of myocardial damage, PCT did not show significant correlations (all p>0.10) with IS (PCT24h: r=0.07; PCT48h: r=0.13) or MVI (PCT24h: r=−0.03; PCT48h: r=0.09). Furthermore, PCT failed to discriminate between large and small IS or MVI or between presence and absence of IMH (AUC values:0.46–0.55).

Conclusions

In the acute phase after PCI for STEMI, circulating PCT remained unaffected by the extent of myocardial and microvascular tissue damage as visualized by CMR imaging. These data highlight the clinical potential of PCT to identify concomitant infections and to guide antibiotic treatments in STEMI patients.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund, Tiroler Wissenschaftsförderung
The inflammasome signaling axis in thrombi from STEMI patients is related to degree of myocardial injury
Authors: Nordeng J , Helseth R , Aakra S , Hoffman P , Schandiz H , Roald B , Bendz B , Arnesen H , Solheim S , Seljeflot I
Published: November 2020

Background

The NLRP3-inflammasome and the IL-6-pathways, i.e. the inflammasome signaling axis, seems to be central mechanisms in the inflammatory response related to myocardial reperfusion injury after revascularization. The beneficial results shown by treating MI-patients with canakunimab, an antibody blocking IL1-β, in the CANTOS trial*, and by treatment of NSTEMI patients with the IL6-receptor antagonist tocilizumab**, are looked upon as proof of concept for inflammasome inhibition.

Purpose

To study whether genes encoding inflammasome-related proteins are present in coronary thrombi and in circulating cells from STEMI patients, and whether these are related to the degree of myocardial injury as measured by troponin T, and time from symptoms to PCI.

Methods

Intracoronary thrombi were aspirated from 33 patients with STEMI treated with primary PCI. The thrombi were snap-frozen in RNA-later solution for gene expression analyses. Peripheral blood samples with Pax-gene tubes were drawn at end of the PCI-procedure. mRNA of NLRP3, caspase1, IL1-β, IL18, IL6, IL6-receptor (IL6-R) and gp130 were isolated from the thrombi and leukocytes in peripheral blood, and relatively quantified by RT PCR. Peak troponin was collected from clinical records.

Results

Genes coding for the 7 different markers were present in 76–100% of the thrombi. The expression of NLRP3 in thrombi significantly correlated to peak troponin T (r=0.468, p=0.024). Dividing peak troponin T values into quartiles, the median value of NLRP3 mRNA in Q4 was 2.0-fold higher compared to Q1–3 (p=0.012). Peak troponin T also correlated with the expression in circulating leukocytes of NLRP3 (r=0.420, p=0.0149) and IL1-β (r=0.394, p=0.023), and borderline to caspase1 (r=0.321, p=0.069) and IL18 (r=0.310, p=0.079).

IL6-R expression in thrombi correlated significantly to peak troponin T (r=0.434, p=0.019), with a 2.5-fold higher median level in Q4 vs Q1–3 of troponin T (p=0.017). gp130 expression in thrombi correlated inversely with peak troponin T (r=−0.398, p=0.050), as did IL6-R expression in circulating leukocytes (r=−0.421, p=0.015). There were no significant correlations between genes expressed in the thrombi and time from symptom to PCI (median 152 minutes), whereas genes for IL6 in circulating leukocytes correlated inversely (r=−0.385, p=0.027).

Conclusion

The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI. Genes encoding NLRP3 and IL6-R were increasingly expressed in thrombi from patients with increased myocardial damage, measured by troponin T, supporting the beneficial effects of medically targeting this pathway.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Stein Erik Hagens Foundation for Clinical Heart Research
Meta-inflammation in monocytes of patients with Acute Coronary Syndrome
Authors: Canonico F , Vinci R , Pedicino D , Pisano E , Ciampi P , Bonanni A , Ponzo M , D'Aiello A , Di Sario M , Severino A , D'Amario D , Niccoli G , Biasucci L.M , Crea F , Liuzzo G
Published: November 2020

Background

Several studies suggest that an alteration of monocyte metabolism might be implicated in inflammatory diseases. Enhanced glycolysis might be a hallmark of pro-inflammatory monocyte subsets. Improved glycolysis enables the immune cells to generate sufficient ATP and biosynthetic intermediates to carry out its particular effector functions. For macrophages this includes phagocytosis and inflammatory cytokine production. Pyruvate Kinase isozyme M2 (PKM-2) catalyzes the final step of glycolysis producing pyruvate and ATP. Latest studies have shown that a member of Jumonji family (JMJD8) acts as a positive regulator in TNF-induced NF-kB signaling leading to pro-inflammatory pathways in macrophages and is involved in angiogenesis and cellular metabolism through interacting with PKM-2 in endothelial cells.

Purpose

The aims of the study are to assess the expression of the glycolytic key enzyme PKM-2 in CD14+ monocytes obtained from patients with non-ST-elevation myocardial infarction (NSTEMI) or with stable angina (SA). Furthermore, the expression of JMJD8 was evaluated.

Methods

30 patients with NSTEMI and 30 patients with SA were enrolled. Peripheral blood mononuclear cells were obtained from whole blood samples. For cytoplasmatic protein identification, cells were fixed and permeabilized and then incubated with fluorochrome-conjugated mAbs anti-CD14, anti-PKM-2 and anti-JMJD8. For analysis we used Two-tailed Mann-Whitney non parametric Comparison test.

Results

CD14+ monocytes from NSTEMI patients showed reduced expression of the key glycolytic enzyme PKM-2 as compared to CD14+ monocytes from SA patients (p=0.02) (Figure 1). JMJD8 expression in NSTEMI patients is increased compared with SA patients (p=0.02) (Figure 2).

Conclusion

This study introduces a role for immune-metabolism in the immunity dysregulation described in ACS patients and provides novel insights into the mechanisms responsible for coronary instability. Taking their potential interaction into account, our data suggest that in acute setting glycolysis key enzyme PKM2 expression is downregulated. Besides, JMJD8 protein levels increase in NSTEMI patients acting as potential limiting factor of PKM2 function. Moreover, our data propose the potential roles of immune-metabolism to detect novel therapeutic targets, associated with an accurate patient stratification based on immune-metabolic profiles, for prevention and treatment of atherosclerosis, in the perspective of a personalized medicine approach.

Funding Acknowledgement

Type of funding source: Private hospital(s). Main funding source(s): Fondazione Policlinico A. Gemelli
Effect of postprandial hyperglycaemia on culprit plaque rupture in diabetic patients with non-ST segment elevation acute coronary syndrome
Authors: Su G , Zhuang S.W , Zhang T , Yang H.X , Dai W.L , Mi S.H
Published: November 2020

Background

Postprandial hyperglycemia was reported to play a key role in established risk factors of coronary artery diseases (CAD) and cardiovascular events. Serum 1,5-anhydroglucitol (1,5-AG) levels are known to be a clinical marker of postprandial hyperglycemia and short-term glycemic excursions. Low serum 1,5-AG levels have been associated with occurrence of CAD; however, the relationship between 1,5-AG levels and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate 1,5-AG as a predictor of coronary plaque rupture in diabetic patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS).

Methods

A total of 132 diabetic patients with NSTE-ACS were included in this study. All patients underwent intravascular ultrasound examination, which revealed 38 patients with plaque rupture and 94 patients without plaque rupture in the culprit lesion. Fasting blood glucose (FBS), hemoglobin A1c (HbA1c) and 1,5-AG levels were measured before coronary angiography. Fasting urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) level was measured and corrected by creatinine clearance.

Results

Patients with ruptured plaque had significantly lower serum 1,5-AG levels and a tendency of higher hemoglobin A1c levels than patients without ruptured plaque in our study population. In multivariate analysis, low 1,5-AG levels were an independent predictor of plaque rupture (odds ratio 3.3; p=0.006) in diabetic patients with NSTE-ACS, but HbA1c was not. The area under the receiver-operating characteristic curve for 1,5-AG (0.678, p=0.001) to predict plaque rupture was superior to that for HbA1c (0.618, p=0.034). Levels of 1,5-AG were significantly correlated with urinary 8-iso-PGF2α (r=−0.224, p=0.010).

Conclusions

Postprandial hyperglycaemia appeared to be superior to long-term average blood glucose levels in predicting plaque rupture in culprit lesions, which may be useful to assess the cardiovascular outcomes in diabetic patients.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Outstanding Clinical Discipline Project of Shanghai Pudong, Beijing Health Special Foundation
Efficacy of early intravenous landiolol, an ultrashort-acting beta-blocker on infarct size and its safety in patients with myocardial infarction undergoing primary PCI: a randomized, controlled study
Authors: Miyamoto M , Miyoshi T , Osawa K , Mori A , Oka T , Ito H
Published: November 2020

Background

Previous clinical studies showed that early intravenous metoprolol before reperfusion in patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI reduced infarct size. However, intravenous beta-blockers in acute phase of STEMI can be associated with adverse effects such as cardiogenic shock and atrioventricular block. Landiolol is an ultrashort-acting beta-blocker with a half-life of 3 min that is eight times more cardioselective than esmolol.

Purpose

We evaluate the efficacy of intravenous infusion of landiolol on infarct size and its safety in STEMI patients undergoing primary PCI.

Methods

This study is a multicenter randomized control trial. A total of 47 patients with Killip class II or less STEMI undergoing PCI within 12 hours of symptoms onset were randomized to receive intravenous landiolol (n=23) or not (control, n=24). Patients allocated to landiolol group delivered an intravenous continuous dose of 3μg/min/kg before reperfusion and then continued until a total dose of 50mg. All patients started oral metoprolol or carvedilol within 12 hours. The primary end point was myocardial salvage index (MSI) on magnetic resonance imaging performed 5 to 7 days after PCI. MSI was defined as the difference between the area at risk and the area of necrosis analyzed using a commercial software.

Results

Magnetic resonance imaging was performed in 35 patients (17 patients in landiolol group and 18 patients in the control group), and ischemia duration time was 229 minutes in the landiolol group and the 242 minutes in control. In adjusting for confounding variables, the areas of myocardium at risk were not difference in both groups (54.4g in the landiolol group, and 46.8g in the control group; p=0.31). However, MSI in the landiolol group was significantly reduced than that in the control group (36.8% and 57.0%; p<0.001).

In both group blood pressure was not difference in recruitment (142mmHg in landiolol group, and 144 in control) and starting PCI (163mmHg in landiolol group, and 165 in control). Regarding safety, the composite of death, malignant ventricular arrhythmia, cardiogenic shock, and atrioventricular block at 24 hours did not differ between the landiolol and the control groups (8.7% and 8.3%, respectively, p=0.93).

Conclusion

Early intravenous landiolol before starting primary PCI reduced infarct size in STEMI patients without significant hemodynamic adverse effects.

Funding Acknowledgement

Type of funding source: None
Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction
Authors: Legallois D , Macquaire C , Hodzic A , Allouche S , El Kouakhi I , Manrique A , Milliez P , Saloux E , Beygui F
Published: November 2020

Background/Introduction

Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome. Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF).

Purpose

We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion.

Methods

Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and at follow-up (7 months). We compared 3 groups: a group with a low-level of plasma neprilysin (<125 pg/mL, i.e. the lower limit of detection of the assay, 38 patients) and the two other groups were defined as being below or above the median value of the remaining samples (15 patients each).

Results

Median age was 58.5±12.8 years and 56 (82.4%) were men. Median LVEF was 45.0±8.5%. Baseline characteristics were comparable among groups. At baseline there was a non-significant trend towards lower end-diastolic volume (p=0.07) but significantly lower LVEF in the high neprilysin group (46.4±8.3%, 47.1±8.1% and 39.1±6.9%, p<0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p=0.022 for relative change in LVEF and 6.6±7.3%, 3.6±9.0% and 11.3±8.4%, p=0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0±8.9%, 50.6±9.7% and 50.4±9.9%, p=0.55).

Conclusion(s)

Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up.

Funding Acknowledgement

Type of funding source: None
The association of acute-to-chronic glycemic ratio with no-reflow in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention
Authors: Simsek B , Cinar T , Tanik V.O , Inan D , Zeren G , Avci I , Gungor B , Yilmaz F , Tanboga I.H , Karabay C.Y
Published: November 2020

Introduction

In the present study, we investigate the association of acute-to-chronic (A/C) glycemic ratio with no-reflow (NR) development in ST elevation myocardial infarction (STEMI) patients following primary percutaneous coronary intervention (PCI).

Material and methods

This retrospective study included 905 consecutive STEMI patients who were treated with primary PCI. The A/C glycemic ratio was determined as admission blood glucose (ABG) divided by the estimated average glucose (eAG). We evaluated two primary models (full model and reduced model).The primary outcome was the presence of NR.

Results

The incidence of NR was 22.7% (206 cases) in the present study. We divided the study population into three tertiles (T1, T2, and T3) based on the ABG/eAG ratio. There was a stepwise increase of the frequency of NR development from the T1 to T3 group (36 patients [12%] vs. 70 patients [23%] vs. 100 patients [33%]; respectively [p <0.001, for each group comparison]). In a full model, the ABG/eAG ratio (OR; 2.274, 95% CI; 1.587–3.26, p<0.001) was associated with NR. After the performance of a step-down backward variable selection method, the thrombus grade, the ABG/eAG ratio, the infarct-related artery diameter, and age remained in the reduced model. The ABG/eAG ratio (contributing 25.3% of the explainable outcome in the model) was one of the strong predictors of NR in the reduced model.

Conclusion

To the best of our knowledge, this might be the first study showing a significant relationship between the ABG/eAG ratios with NR in STEMI patients after primary PCI.

Figure 1

Funding Acknowledgement

Type of funding source: None
Compared prognostic impact of incident atrial fibrillation versus history of atrial fibrillation in patients with AMI: the FAST-MI programme
Authors: Danchin N , Fauchier L , Marijon E , Lavergne T , Boveda S , Martinet M , Defaye P , Piot O , Puymirat E , Bataille V , Drouet E , Ferrieres J , Schiele F , Simon T
Published: November 2020

Background

History of atrial fibrillation (HxAF) and new onset atrial fibrillation (NOAF) at acute stage of MI are associated with poorer survival. Whether both entities carry an increased risk of stroke is uncertain.

Using data from the FAST-MI 2010 and 2015 registries, we analysed the associations between HxAF and NOAF and risk of 3-year death, nonfatal stroke or combined death or stroke.

Methods

The FAST-MI registries are nationwide French cohorts consecutively including AMI patients admitted over a 1-month period every 5 years. Baseline characteristics, acute management and medications at discharge are collected. Among 9460 patients with STEMI or NSTEMI, 610 (6.4%) had HxAF, and 626 (6.6%) developed NOAF.

Main characteristics

Table 1 Overall, NOAF was associated with larger and more severe AMIs.

Results

In hospital survivors, 3-year death was 8.6% in patients without AF, 23.2% in those with NOAF and 29.2% in those with HxAF. 3-year Kaplan-Meier rates of non-fatal stroke were 1.1%, 0.3% and 3.6%, respectively (Figure).

Compared with no AF, NOAF was not associated with non-fatal stroke (Cox HR, 95% CI: 0.17, 0.02–1.21), while HxAF was (HR, 95% CI 2.04, 1.13–3.66, P=0.017). Risk of death or stroke was increased for both NOAF (HR, 95% CI 1.35, 1.10–1.65, P=0.004) and HxAF (HR 95% CI, 1.37, 1.14–1.65, P=0.001). Risk of all-cause death at 3 years was increased for NOAF (HR, 95% CI 1.32, 1.09–1.60) and HxAF (HR, 95% CI 1.30, 1.09–1.55). The results were concordant in patients not receiving oral anticoagulants at discharge.

Conclusion

Both NOAF and HxAF are associated with increased risk of death at 3 years after AMI. NOAF, however, is not associated with an increased risk of non-fatal stroke.

Figure 1. Non-fatal stroke

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Pharma companies
Long-term predictors of myocardial infarction recurrence in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention
Authors: Silverio A , De Angelis E , Cancro F.P , Di Maio M , Esposito L , Romei S , Citro R , Ciccarelli M , Vecchione C , Galasso G
Published: November 2020

Background

Despite the implementation in the use of primary percutaneous coronary intervention (pPCI) and in secondary preventive measures, the risk of recurrence of myocardial infarction (MI) in patients who underwent ST-elevation myocardial infarction (STEMI) remains high. The prognostic role of old and emerging cardiovascular risk factors for MI recurrence, such as Lipoprotein(a) [Lp(a)] levels, in this very high-risk population is still not fully understood.

Purpose

To identify the baseline predictors of MI recurrence in a cohort of patients admitted for STEMI and treated with pPCI.

Methods

Single-center, observational, retrospective analysis of consecutive patients admitted for STEMI who underwent pPCI from February 2013 to April 2019 at our Insitution. Baseline demographic, clinical, echocardiographic and laboratory data were prospectively collected. Only patients with available Lp(a) values were included in the analysis.

The study outcome was the recurrence of MI at three years follow-up. Univariable and multivariable Cox regression analysis was performed to identify the baseline variables correlated to the study outcome.

Results

The study population included 560 patients (mean age = 60.6±13.7 years; 79.5% males). Hypertension was observed in 351 patients (62.7%), diabetes in 134 (23.9%), dyslipidemia in 266 (47.5%), smoking status in 316 (56.4%), history of coronary artery disease (CAD) in 76 (13.6%), prior MI in 69 (12.3%), prior PCI in 62 (11.1%). Multivessel disease (MVD) was reported in 211 (37.7%) cases. The infarct-related artery was the left anterior descending in 310 patients (55.4%), the right coronary artery in 179 (32.0%), the left circumflex 60 (10.7%) and the left main in 11 (2.0%). Total cholesterol mean value was 187.7±48.8 mg/dl; LDL cholesterol was 112.2±41.3 mg/dl and Lp(a) was 26.5±27.2 mg/dl. At three-year follow-up, MI occurred in 58 (10.4%) patients. At multivariable analysis, Lp(a) (HR 1.015 95% CI: 1.008–1.022 p<0.001) and MVD (HR 1.994; 95% CI 1.179–3.372 p=0.010) emerged as the only two independent predictors of MI recurrence up to three years. The Kaplan-Meier analysis showed a significantly lower survival free from MI in patients with Lp(a) ≥50 mg/dl as compared to the subgroups with levels ≥30 and <50 mg/dL, or <30 mg/dL (Log-Rank=0.001). Also, MVD was able to identify patients with significantly lower survival free from MI for up to three years (Log-Rank=0.004). The Kaplan-Meier analysis combining these two parameters identified patients with both MVD and Lp(a) ≥50 mg/dl as the highest risk cohort for MI recurrence up to three years (MI incidence rate=22.2%; Log-Rank=0.002).

Conclusions

Among patients with STEMI who underwent pPCI, high Lp(a) level and MVD predict the recurrence of MI at long-term follow-up.

Funding Acknowledgement

Type of funding source: None
Predictive factors of a prolonged total ischemic time in patients presenting with ST-segment elevation myocardial infarction
Authors: Lopez Lluva M.T , Jurado Roman A , Lozano Ruiz Poveda F , Abellan Huertas J , Frias Garcia R , Sanchez Perez I
Published: November 2020

Introduction

Total ischemic time (TIT), the time from symptom onset to therapeutic reperfusion of infarcted myocardium is a key factor in the treatment of patients with ST-segment elevation myocardial infarction (STEMI). The identification of the predictive factors of a prolonged TIT will allow design specific strategies to optimize this time and improve the quality of care of these patients. Our objective was to evaluate independent factors predicting prolonged TIT.

Methods

We performed a prospective observational study, with consecutive inclusion of all patients presenting within 24 hours of symptom onset of STEMI (n=546), transferred to our center for primary percutaneous coronary intervention (pPCI).

Results

The median TIT was 190 (137–281) minutes. No significant differences were found according to the year of study. In the univariate analysis, age showed a slight trend (p=0.05); for each year that is increased, the TTI increases 1.3 minutes. Women had higher TII than men [219 (145–332) vs. 187 (133–270) minutes; p=0.02]. No statistically significant differences were found in relation to the presence of cardiovascular risk factors. Patients treated during non-working hours had shorter TIT than those treated during working hours [179 (130–252) vs. 202 (142–307) minutes; p=0.03]. The distance to a 24h-PCI hospital was an independent predictive factor. Those patients whose first medical contact (FMC) was in a non-PCI-capable hospital or in a clinic showed the highest TIT [226 (147–336) and 205 (146–304) minutes, respectively; p<0.001]. Patients with initial non-diagnostic ECG presented a significantly longer TIT (p<0.001) than patients correctly diagnosed since the beginning, with a median difference of 188 minutes. A trend was observed for the Killip-Kimball classification variable (p=0.07). Patients with previous infarction had shorter TIT compared to those who have never had it (p=0.02). In the multivariate binary logistic regression analysis, the variables: initial non-diagnostic ECG, FMC (in a non-PCI-capable hospital or clinic) and the distance to 24h-PCI hospital (>90 km) were independent predictive factors of a TIT >180 minutes. An initial non-diagnostic or misinterpreted ECG sextuples the risk of a prolonged TIT.

Conclusions

In our area, the total ischemic time is determined by a non-diagnostic or misinterpreted EKG, the first medical contact and the distance to a 24h-PCI hospital.

Funding Acknowledgement

Type of funding source: None
Clinical outcome of patients with ST-elevation myocardial infarction and angiographic evidence of coronary artery ectasia
Authors: Silverio A , Esposito L , Fierro G , Di Maio M , Di Feo F , Iannicelli A , Varone M , Vigorito F , Maione A , Di Muro M.R , Attisano T , Vecchione C , Galasso G , Baldi C
Published: November 2020

Background

Coronary artery ectasia (CAE) is a relatively frequent finding in patient with ST-elevation myocardial infarction (STEMI) who undergo emergent coronary angiography. However, the long-term outcome of STEMI patients with CAE as compared to Non-CAE has been poorly investigated.

Purpose

To compare the baseline features and outcome of patients with and without CAE in the clinical setting of STEMI.

Methods

All patients with STEMI who underwent emergent coronary angiography from January 2012 to December 2017 at our Institution were retrospectively enrolled. Baseline demographic, clinical, instrumental, angiographic and percutaneous coronary intervention (PCI) findings were collected for patients with and without CAE. The study outcome measures were recurrent myocardial infarction (MI) and all-cause death. The propensity score weighting (PSW) technique was used to take into account for potential selection bias in treatment assignment between CAE and Non-CAE groups.

Results

The study included 534 patients with STEMI (mean age 62.9±12.0 years), 154 were CAE and 380 Non-CAE. The two groups were significantly different in terms of sex (90.9% in CAE vs 72,6% in Non-CAE, p<0.001), diabetes (11.7% vs. 25.8%; p=0.009) and smoking status (72.1% vs. 62.4%; p=0.042). The right coronary artery was more commonly treated in CAE patients (41.6% vs. 30.8%, p=0.023) and, as expected, the stent diameter (p<0.001) and the TIMI frame count (p<0.001) were significantly higher in CAE group. The myocardial blush grade was higher in Non-CAE (p<0.001). The Kaplan-Meyer analysis showed a comparable rate of all-cause death among the two groups (3.4/100 person/years in CAE vs. 3.5 per 100 person/years in Non-CAE, Log-Rank = 0.86).

The survival free from recurrent MI was lower, although not statistically significant, in CAE vs. Non-CAE patients (3.1/100 person/years vs. 4.8/100 person/years; Log-Rank = 0.068).

After PSW, an optimal balance was obtained as demonstrated by a standardized mean difference <0.1 for all the variables included in the model. The adjusted Cox regression analysis showed a significantly higher risk of recurrent MI in CAE vs. Non-CAE groups (HR = 1.93; p=0.009). No difference in the risk of all-cause death was observed (HR = 0.83, p=0.501).

Conclusions

Patient with STEMI and angiographic evidence of CAE have a different clinical profile compared to Non-CAE. In this analysis focused on STEMI patients, CAE was associated with a higher risk of recurrent MI at long-term follow-up.

Funding Acknowledgement

Type of funding source: None