bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological preconditioning by Nicorandil in prevention of ischaemic myocardial injury during an elective percutaneous coronary intervention
Authors: Soboleva G , Gostishev R.V , Rogoza A.N , Kotkina T.I , Samko A.N , Soboleva T.V , Karpov Y.A
Published: November 2020

Introduction

Elective percutaneous coronary intervention (PCI) is accompanied by intraoperative ischemic myocardial injury (IIMI) up to 30% of the cases despite successfully performed procedure. Pharmacological preconditioning can prevent IIMI; Nicorandil is considered promising for this purpose.

Purpose

To study the possibility of pharmacological preconditioning by oral Nicorandil to ptevent ischaemic myocardial injury and 4a type myocardial infarction (MI) in patients with a stable form of coronary artery disease (CAD) before PCI.

Material and methods

182 patients with CAD and indications for PCI were randomized into two groups: Nicorandil treatment group (additionally to β-blockers and a calcium channel blockers, n=90) and the control group (β-blockers and a calcium channel blockers, n=92). Nicorandil per os was prescribed 2 days before the PCI (30 mg/day); on the day of PCI – 2 hours before intervention (20 mg), 6–12 hours after PCI – 10 mg. The analysis of hs-Troponin I (hs-Tr) and creatine phosphokinase-MB (CK-MB)was carried out before PCI and 24, 72 hours after the procedure. The diagnosis of MI 4a type was established according to fourth universal definition. Double antiplatelet therapy was prescribed to all patients.

Results

Clinical profile (age, BMI, BP, creatinin clearance, LDL-cholesterol, glucose) of the patient groups were comparable by the basic parameters. The rate of hs-Tr after 24 hours has approached the 99th percentile from the upper limit of normal in 146 patients (80%). The increment of mean level of hs-Tr 24 hours after PCI has not distinguish statistically between the Nicorandil and the control group (364 vs 725 pg/ml, p=0,1). Mean of CK-MB increment in the control group has approached 2,5 ng/ml vs 0,5 ng/ml in the Nicorandil group (p=0.06). Among women (n=61), the increment of hs-Tr in 24 hours after PCI was statistically significantly lower (287 vs 1135 pg/ml, p=0,04) in the Nicorandil group compared to the control group. MI 4a type was detected in 12% of patients in the control group, and it decreased to 3% of patients in the Nicorandil group (p=0,05), it was observed in 21% in women in the control group and in 3% in the Nicorandil group.

Conclusion

Nicorandil treatment using before PCI decreases the risk of MI 4a in patients with a stable CAD due to the realization of pharmacological preconditioning.

Funding Acknowledgement

Type of funding source: None
Clinical outcomes of percutaneous coronary intervention in coronary allograft vasculopathy from single center experience
Authors: Cia Mendioroz X , Oteo Dominguez J.F , Leon Aliz E , Vilches-Soria S , Arellano Serrano C , Garcia-Touchard A , Fernandez Diaz J.A , Caraballo Gomez M.A , Goicolea Ruigomez J , Segovia Cubero J
Published: November 2020

Background/Introduction

Cardiac allograft vasculopathy (CAV) is a leading cause of morbidity and mortality of heart transplant recipients. Percutaneous coronary intervention (PCI) is an alternative to medical treatment, however long-term data from large multicenter studies are scarce.

Purpose

To review clinical characteristics and outcomes of CAV undergoing PCI in our heart transplant series.

Methods

We analysed retrospectively 52 heart transplant recipients with CAV who underwent PCI from 2004 to 2020. Surveillance angiography was performed in 90% of stents. Stent restenosis (SR), stent thrombosis (ST), target lesion revascularization (TLR) and patient survival are reported.

Results

During study period, 124 lesions were treated. Primary success was obtained in 99% of lesions. Mean angiographic follow up was 37±47 months. A total of 31 (25%) stents presented events during follow-up: 24 SR, 7 ST. There were no differences between bare-metal stent (BMS) and drug-eluting stent (DES). We performed 16 (12.9%) TLR. There was no association between clinical and lesion-related features and TLR. Post-PCI survival was 75.3% at 5 and 55.7% at 10 years.. Cytomegalovirus (CMV) infection before development of CAV decreased survival in univariable analysis (p<0.016).

Conclusions

PCI with stent in CAV can be performed with high rates of primary success and low rate of complications, similar to non-transplant patients. Our series suggest that CMV infection can have negative impact in post-PCI survival, but further studies are needed.

Funding Acknowledgement

Type of funding source: None
Prediction of medium term mortality in diabetics with complex ischemic heart disease after first isolated coronary artery bypass grafting: comparison of FREEDOM, SYNTAX II and our formula
Authors: Ostojic M , Arnautovic N , Nezic D , Borzanovic M , Ragus T , Nikolic A , Micovic S , Otasevic P , Djokic D , Ivanovic I , Stanetic B , Kovacevic-Preradovic T , Tasic N , Djajic V , Bojic M
Published: November 2020

Background

Controversies exist how to predict medium term mortality (Mt) in diabetics (DM) with 3 vessel (3VD) and/or left main (LM) disease undergoing myocardial revascularization ranging from Syntax Score II (SSII) where DM was not predicative variable up to FREEDOM formula which was derived, just from population with DM (without LM), having DM patients (Pts) requirement of insulin as one of predicative variable.

Purpose

To compare predicative power of SSII, FREEDOM and formula developed in our institution in Pts post first isolated CABG with 3VD and/or LM with DM.

Methods

From our prospective data base of 2455 consecutive pts who had the first isolated CABG in the period 01/2012–12/2014 with complex Ischemic Heart Disease with 100% follow up of 4 years all-cause Mt we created by random sampling Training (1321; Mt:10.4%; DM 511; Mt:13.3%) and Validation (1134; Mt:10.0%; DM 414; Mt: 11.8%) sets. After deriving predicative formula (Cox regression) from training population we validated FREEDOM, SSII and Our Formula in 414 pts with DM from the Validation set.

Results

Characteristics of pts, our formula, predicating power by C Statistics, Calibration plots and Brier scores are presented in Picture 1.

Conclusions

FREEDOM formula designed just for DM pts with complex Ischemic Heart Disease without LM had the smallest standard error in the estimate, but moderate C statistics as Syntax Score II and our formula which may be used for pts with and without DM and 3VD and/or LM.

Picture 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of education, science and technology development, Republic of Serbia
FREEDOM formula: external validation of diabetics treated by coronary artery bypass grafting in single large volume cardio-surgical center
Authors: Arnautovic N , Ostojic M , Nezic D , Borzanovic M , Nikolic A , Ragus T , Micovic S , Otasevic P , Djokic D , Ivanovic I , Stanetic B , Kovacevic-Preradovic T , Djajic V , Tasic N , Bojic M
Published: November 2020

Background

Freedom formula (FF) was derived very recently to assist in decision making by Heart Team in patients (Pts) with diabetes (DM) who are in need for myocardial revascularization (Percutaneous Coronary Intervention or Coronary artery bypass grafting (CABG)) due to complex ischemic Heart disease (but without left main steam disease (LM)). In external validation moderate C statistics values were obtained.

Purpose

To validate FF predictive value in Pts with DM and more complex patients (three vessel (3VD) and/or LM as well lower left ventricular ejection fraction (LVEF)) than in FREEDOM population.

Methods

From our prospective data base of 2455 consecutive pts who had the first isolated CABG in the period 01/2012–12/2014 with 3VD and/or LM with 100% follow up of 4 years All-cause Mortality (Mt) we retrieved 925 pts with DM.

Results

DM was present in 925 Pts (Mt: 12.6%). On insulin were 318 (34.3%; Mt 14.5%). We analysed the predicative value of FF in the whole group (925) of pts with DM as well as in subgroups with LM (294) and without LM (631; most similar to original Freedom population), separately. Characteristics of pts, Freedom formula, predicating power by C Statistics, Calibration plots and Brier scores are presented in Picture 1.

Conclusions

Our external validation of FF was almost identical as previous published one. Furthermore, the FF may be of value even in pts with LM disease and other vessels involved. Of note our pts as seen by combined LVEF, ClCr and LM were sicker than pts in FREEDOM.

Picture 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Ministry of education, science and technological development, Republic of Serbia
Expression of adiponectin and il-6 by local fat depots of the heart: relationship with the main risk factors for cardiovascular diseases
Authors: Gruzdeva O.V , Belik E , Dyleva Y.U.A , Borodkina D.A , Uchasova E.G , Sinitsky M.Y.U , Brel N.K , Karetnikova V.N , Bychkova E.E , Barbarash O.L
Published: November 2020

Introduction

Previous studies have identified a number of pro-inflammatory and other markers potentially associated with atherogenesis, which are also expressed and produced by adipose tissue. Atherosclerosis is a multifactorial disease, in the development of which both unmodifiable factors (gender, age) and modifiable factors (smoking, dyslipidemia) contribute, and further study of the pathogenetic relationships of adipocytokines and CVD risk factors is necessary.

Purpose

To evaluate the features of the expression of adiponectin and IL-6 in the epicardial (EAT), perivascular (PVAT), subcutaneous adipose tissue (SAT) and its relationship with the main risk factors for CVD.

Materials and methods

The study included 84 patients with stable coronary artery disease (CAD) who were planning coronary artery bypass grafting (CABG). During the operation, adipose tissue (AT) biopsy samples were obtained. The expression of adiponectin and IL-6 genes was evaluated by the method of quantitative polymerase reaction in real time (PCR) depending on the presence or absence of CVD risk factors.

Results

It was found that adipocytes of EAT are characterized by the lowest expression of the adiponectin gene against the background of the maximum - IL-6. In men, the adiponectin mRNA level in EAT and PVAT is reduced (2.5 and 2.8 times). The expression of IL-6 in male patients is higher in SAT (3 times) and lower in PVAT than in women. The presence of dyslipidemia is associated with a decrease in the expression of both adiponectin in EAT and PVAT (2.7 and 3.6 times), and IL-6 in PVAT (2.3 times). People with arterial hypertension (AH) have lower levels of adiponectin in EAT and PVAT (2 and 1.8 times) with high levels of IL-6 in SAT and EAT (8 and 10.4 times). With an increase in the experience of hypertension for more than 20 years, adiponectin expression decreases in all types of AT with an increase in IL-6 in PVAT (2 times) and a decrease in SAT. Smoking is associated with increased adiponectin mRNA levels. Patients 51–59 years old are characterized by high expression of IL-6 in EAT and PVAT in comparison with parameters of other age groups.

Conclusions

The revealed decrease in the expression of adiponectin in EAT against the background of an increase in pro-inflammatory IL-6 can enhance atherogenesis, and in combination with risk factors such as male sex, the presence of dyslipidemia and hypertension contribute to the progression of coronary artery disease.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Russian Scientific Foundation no. 17-75-20026
Long term outcomes of single versus multi-vessel coronary artery disease in patient with diabetes undergoing PCI
Authors: Omair M , Dinh D.D , Brennan A.B , Farouque O.F , Duffy S.D , Ajani A.J , Andrianopoulos N.A , Koshy A.K , Yudi M.Y , Clark D.C
Published: November 2020

Background

Long-term outcomes of PCI in diabetics with single vessel disease (SVD) are less well known. We aimed to assess the long-term mortality of patients with diabetes with SVD compared to MVD undergoing PCI.

Methods

We included 7,506 consecutive patients with DM undergoing PCI from 34,784 patients in the Melbourne Interventional Group registry (2005–2018).

Results

4,889 (65%) of DM had MVD. Compared to SVD, MVD were older (67±11 vs. 64±11 years), with higher rates of hypertension, insulin dependence, renal impairment, left ventricular ejection fraction <45% and cardiogenic shock (all p<0.001). Patients with MVD had significantly higher rates of stent thrombosis, unplanned CABG and major bleeding (all p<0.001). Unadjusted mortality rates in hospital, at 30 days and long-term (mean 5.4±3 years) were higher in MVD (4.1 vs 1.4%, 4.9% vs 1.9%, 26% vs 16.4%; all p<0.001). Cox proportional hazard modelling found MVD as an independent predictor of long-term mortality (HR 1.7, 95% CI 1.5–1.9, p<0.001). Long term mortality was similar for SVD diabetes and MVD non-diabetes (HR 1.29, 95% CI 1.13–1.48 vs 1.26, 95% 1.16–1.37), which was also evident on Kaplan-Meier curve.

Conclusion

DM with SVD undergoing PCI had a lower long-term mortality. However, the mortality beyond 5 years in SVD increases, mandating aggressive risk factor control and close clinical follow-up.

Kaplan-Meier curve

Funding Acknowledgement

Type of funding source: None
Acute coronary syndromes in chronic kidney disease patients: the good, the bad or the ugly?
Authors: Saleiro C , De Campos D , Lopes J , Teixeira R , Sousa J.P , Gomes A.R.M , Puga L , Costa M , Goncalves L
Published: November 2020

Background

Patients with chronic kidney disease (CKD) are at increased risk of composite cardiovascular (CV) events and all-cause mortality. However, current aggressiveness of therapeutic strategies may minimize the course of the disease.

Aim

To assess the prognostic impact of optimized medical treatment in a CKD population with acute coronary syndrome (ACS).

Methods

355 ACS patients admitted to a single coronary care with CKD who were discharged from hospital were included. Those with end-stage renal disease were excluded. Three groups were created based on the KDIGO classification: Group A (Stage 3A, eGFR [estimated glomerular filtration rate] 45–59mL/min/1.73 m2) N=190; Group B (Stage 3B, eGFR 30–44mL/min/1.73 m2) N=113; and Group C (Stage 3B, eGFR 15–29mL/min/1.73 m2) N=52. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The median of follow-up was 32 (IQ 15–70) months.

Results

Groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, left ventricular (LV) systolic function, peak troponin, multivessel disease, treatment option (PCI, CABG or OMT) and medical therapy at discharge. More advance renal failure patients had a higher prevalence of diabetes mellitus (DM), a lower haemoglobin, a higher NT-proBNP and were less likely to receive ACE inhibitors/angiotensin II antagonist at discharge. 170 patients met the primary outcome. Kaplan-Meyer curves showed decreased survival with worse renal function (Group A 68% vs Group B 57% vs Group C 37%, Log Rank P=0.006 – Figure 1). After adjustment for age, DM, haemoglobin, NT-proBNP, LV systolic function and ACE inhibitors/angiotensin II antagonist at discharge, eGFR was not associated with increased death (HR 1.00, 95% CI 0.98–1.01). In this model, only age (HR 1.04, 95% CI 1.01–1.07), haemoglobin (HR 0.86, 95% CI 0.979–0.94), Nt-proBNP (HR 1.00, 95% CI 1.00–1.00) and impaired LV function (LV ejection fraction 40–49%: HR 2.95, 95% CI 1.89–4.81; LV ejection fraction <40%: HR 2.15, 95% CI 1.44–3.21) remained associated with the outcome.

Conclusion

The worse outcome attributed to CKD after an ACS seems to be related not the eGFR itself but to associated comorbidities such as age, anaemia, fluid overload and impaired LV function. The fact that some of these comorbidities may be altered by intensive therapy indicates that CKD patients should also be candidates to optimized medical treatment.

Funding Acknowledgement

Type of funding source: None
Moment of truth for aspirin use in variant angina: a meta-analysis
Authors: Sousa J.P , Puga L , Lopes J , Saleiro C , Gomes R , Lourenco C , Goncalves L
Published: November 2020

Background

Aspirin has been a mainstay of antiplatelet therapy for coronary artery disease (CAD). However, in the context of variant angina (VA), high-dose aspirin was reported to exacerbate coronary spasms. Consequently, the value of traditional low-dose aspirin in VA, especially if not associated with atherosclerotic CAD, may be disputed.

Purpose

To perform a meta-analysis aimed at evaluating the extent to which low-dose aspirin therapy influences cardiovascular (CV) prognosis in VA.

Methods

We systematically searched MEDLINE, Embase, Web of Science, Cochrane Library and Google Scholar for studies addressing the long-term impact of low-dose aspirin on main CV outcomes of VA patients, published up until February 1, 2020. The primary endpoint was all-cause mortality, whereas secondary endpoints included CV mortality, acute coronary syndrome (ACS) events, revascularization procedures and hospital admissions for angina. The subgroup of patients with no significant epicardial CAD was further investigated separately, underneath similar outcomes. Study-specific odds ratios (ORs) were pooled using traditional meta-analytic techniques, under a random-effects model.

Results

One prospective multicenter and two retrospective single-center studies, encompassing 1652 and 1164 patients, respectively, were regarded as eligible for quantitative evaluation. Median follow-up ranged between 12 and 52.1 months. 1284 patients were allocated to the aspirin arm and 2770 had no epicardial CAD. Absolute number of events for each endpoint may be reported as follows: all-cause mortality, 33; CV mortality, 11; ACS, 57; revascularization, 14; hospital admission for angina, 218. Aspirin was not found to reduce neither all-cause mortality (OR 0.78, 95% CI 0.38–1.58, p=0.49, i2=0%), nor CV mortality (OR 0.98, 95% CI 0.30–3.25, p=0.98, i2=0%), nor ACS events (OR 1.44, 95% CI 0.51–4.10, p=0.49, i2=47%), nor revascularization procedures (OR 2.06, 95% CI 0.63–6.75, p=0.23, i2=0%), nor hospital admissions for angina (OR 1.60, 95% CI 0.67–3.80, p=0.29, i2=86%). Likewise, this comprehensively neutral effect held true in those with VA and no significant atherosclerotic CAD (OR 1.04, 95% CI 0.28–3.92, p=0.95, i2=0%, for CV mortality; OR 1.29, 95% CI 0.19–8.94, p=0.79, i2=33%, for revascularization; OR 1.73, 95% CI 0.81–3.73, p=0.16, i2=75%, for hospital admission for angina).

Conclusion

Even though scarce, currently available evidence suggests that low-dose aspirin is not effective in shrinking major adverse cardiovascular events in VA patients, particularly in those with no epicardial CAD. On the other hand, lower doses of aspirin may avoid the menace of clinically significant coronary spasms.

Funding Acknowledgement

Type of funding source: None
Prevalence of thrombophilia and antiphospholipid syndrome in myocardial infarction with non-obstructive coronary arteries and cryptogenic stroke
Authors: Kruchinova S
Published: November 2020

The role of thrombophilia in myocardial infarction without obstructive coronary artery disease (MINOCA) is unclear.

We investigated thrombophilic factors in patients with MINOCA in comparison with a group of patients with cryptogenic stroke.

Methods

92 patients (mean age: 52.5 years) were evaluated at least 2 months after hospitalization for I MINOCA. The control group was age-comparable patients with cryptogenic stroke (n=90) and the group of patients with myocardial infarction with obstructive coronary artery disease (MI-CAD) (n=80). Thrombophilia screening included hereditary thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C, protein S or antithrombin deficiency), antiphospholipid syndrome (APS), along with factor VIII >150%, homocysteine ≥15 μm and lipoprotein (a) ≫30 mg/dl.

Results

Compared to cryptogenic stroke, in the MINOCA group, men were more common among patients (56.2 vs. 33.3%, P<0.001), obesity was more common among risk factors (31.5 vs. 16.9%, P=0.014), smoking (54.2 vs. 39.7%, P=0.042), as well as a burdened family history (18.4 against 7.0%, P=0.004). Hereditary thrombophilia occurred in 25.8% of patients with MINOCA and in 17.1% with cryptogenic stroke (P=0.17). APS was found in 15.5% of MINOCA. APS was diagnosed less frequently in patients with NSTEMI, (2.9 versus 21.3% P=0.002) and in patients with MINOCA aged ≤55 years (4.1 versus 36.3% for the elderly, P=0.005).

Conclusions

In patients with MINOCA, there is a high prevalence of thrombophilia, including APS, similar to cryptogenic stroke. Our first comprehensive study of thrombophilia in MINOCA confirms its clinical significance.

Funding Acknowledgement

Type of funding source: None
High sensitivity C-reactive protein is associated with worse infarct healing after revascularized ST-elevation myocardial infarction
Authors: Tiller C , Reindl M , Holzknecht M , Lechner I , Simma F , Schwaiger J , Mayr A , Klug G , Bauer A , Reinstadler S.J , Metzler B
Published: November 2020

Background

The inflammatory response due to myocardial tissue injury in the setting of acute ST-elevation myocardial infarction (STEMI) is essential for proper local infarct healing. However, an excessive inflammatory response may aggravate myocardial damage and hampers infarct healing processes. The present study aimed to investigate the association of systemic inflammatory biomarkers with infarct size (IS) dynamics post-STEMI, using cardiac magnetic resonance (CMR) imaging.

Methods

This prospective observational study included 245 STEMI patients treated with primary percutaneous coronary intervention (pPCI). Peak values of high-sensitivity C-reactive protein (hs-CRP), white blood cell count (WBCc) and fibrinogen were determined serially until 96 hours after pPCI. Infarct healing, defined as relative IS reduction from baseline to 4 months after STEMI, was assessed using late gadolinium enhanced CMR imaging.

Results

IS significantly decreased from 16% of left ventricular mass (LVM) (Interquartile range [IQR]:8–24) at baseline to 10% (IQR:5–17) at 4 months (p<0.001). Relative IS reduction was 35% (IQR:8–50). Whereas peak WBCc (p=0.926) and peak fibrinogen (p=0.161) were not significantly associated with relative IS reduction, peak hs-CRP showed a significant association with IS reduction (p=0.003). In multivariable logistic regression analysis, the association between peak hs-CRP and relative IS reduction remained significant after adjustment for baseline IS, hypertension, hs-cardiac troponin T and N-terminal pro B-type natriuretic peptide (odds ratio:0.35 [95% confidence interval:0.19–0.63]; p=0.001).

Conclusions

In STEMI patients treated with pPCI, hs-CRP was independently associated with 4 months IS reduction as determined by CMR, suggesting a pathophysiological interplay between inflammation and adverse infarct healing in survivors of acute STEMI.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Austrian Society of Cardiology
Characterizing genetic variants for DAG and IP3 signalling pathways in severe cases of coronary spastic angina
Authors: Shibutani S , Yonekura M , Nosaka M , Kawamura Y , Hanada K , Kasai S , Yokota T , Higuma T , Itoh K , Tomita H
Published: November 2020

Background

We previously reported that the activity of phospholipase C (PLC), a key molecule for intracellular calcium signaling, was enhanced in patients with coronary spastic angina (CSA). Furthermore, we found PLC-δ1 864 G to A mutation in about 10% of the male CSA patients. However, comprehensive understanding of genetic role in the pathogenesis of CSA remains to be elucidated.

Purpose

We tested the hypothesis that variants in the genes responsible for contraction signaling, especially a Ca2+-dependent mechanism, plays an important role in the pathogenesis of CSA.

Methods and results

Exome sequencing was performed to genotype comprehensively CSA cohort, enabling investigation of 258 gene network for diacylglycerol (DAG) and inositol trisphosphate (IP3) signallings, which are responsible for contraction signaling in the vascular smooth muscle cell (VSMC) by a Ca2+-dependent mechanism.

The study population included 30 Japanese patients with severe cases of CSA (18 men and 12 women with a mean age of 62.2±10.1 years). In 23 patients, ST segment elevation was recorded on the electrocardiogram during a spontaneous attack. In other 3 patients, ventricular fibrillation occurred following CSA attacks. The rests were diagnosed by ECG changes and elevated cardiac enzymes following CSA attacks. Genetic information from these CSA patients were compared with those from 914 healthy controls.

Frequencies of 17 common, functional polymorphisms of DAG and IP3 signallings were statistically similar to those of healthy controls. By high-quality (Call Quality ≥20, Read Depth ≥10), and predicted-deleterious (CADD score ≥20) filterings, the number of the candidate genes were narrowed from 234,445 to 17,738, and by selecting genes for DAG and IP3 signallings, further narrowed to 208 genes. Compared with 914 healthy controls, DAG and IP3 signalling genes revealed 26 variants in 15 genes in CSA cases, and by further filtering for rare (914 healthy control frequency <1%), 21 variants in 12 genes were found. They shared variants in G protein subunit alpha q (GNAQ), phospholipase C beta 3 (PLCB3), inositol 1,4,5-trisphosphate receptor type 3 (ITPR3), glutamate ionotropic receptor NMDA type subunit 2D (GRIN2D) in ≥5 cases. By filtering for high-quality, predicted-deleterious, and rare, genetic variants related with DAG and IP3 signalling were more found in severe CSA patients compared with healthy controls (CSA 4.33/person vs healthy controls 2.60 /person).

Conclusions

These findings indicate genetic heterogeneity in CSA susceptibility and a likely polygenic basis, giving a cumulative effect on DAG and IP3 signalling pathways in a subset of individual CSA patients. Study of larger cohorts is warranted to define genetic risk factors for CSA.

Funding Acknowledgement

Type of funding source: None
Participation in a research study related to acute myocardial infarction is not a guarantee to live more longer: results from the FAST-MI registries
Authors: Puymirat E , Schiele F , Roubille F , Tea V , Ferrieres J , Simon T , Danchin N
Published: November 2020

Background

The main potential benefits of participating in a clinical trial is to have access to a treatment that is not available yet and to have a regular and careful attention from physicians. Several data have suggested that inclusion in a research study was associated with better clinical outcome.

Aims

The aim of this study is to describe the prevalence of inclusions in a research study (i.e., device or medication), clinical characteristics, management and clinical outcome in patients admitted for acute myocardial infarction (AMI) according to participation in a research study (versus not) using data from the French registries of Acute ST-or non-ST-elevation Myocardial infarction (FAST-MI) 2010 and 2015.

Methods

We used data from 2 one-month French registries, conducted 5 years apart, including 9,414 AMI admitted to coronary or intensive care units. We analyzed baseline characteristics, management and one-year survival according to participation in a research study.

Results

From 2010 to 2015, the prevalence of patients included in a research study decreased from 6.8% to 3.6% (P<0.001). Inclusions were performed mainly in university hospitals (8%). Clinical characteristics according to participation in a research study were strongly different. Overall, patients included in a research study were younger (61.2±12.7 vs 65.7±14.1; P<0.001) with less previous medical history and co-morbidities. Clinical presentation was preferentially a ST-elevation myocardial infarction (STEMI: 70% vs 52%; P<0.001) in these patients who had a lower GRACE score (133±32 vs. 141±35; P<0.001). The use of invasive strategies was more used in patients included in a research study (coronary angiogram: 99% vs 95%, P<0.001) as prescriptions of recommended medications (i.e., antiplatelet agents, beta-blockers, angiotensin-converting-enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) and statins) at discharge (72% vs 63%; P<0.001).

In a cox multivariate analysis, participation in a research study was not associated with lower mortality at one-year (HR= 0.68, 95% CI, 0.39–1.18, P=0.17). Similar results were observed in patients discharge alive (HR= 0.81, 95% CI, 0.44–1.48, P=0.49). Recommended medications were however more used in patients included in a clinical trial (OR=1.34; 95% CI, 1.09–1.65; P=0.007).

Conclusions

The number of inclusions in a research study related to AMI in France is low. Our data suggest that patients included in a research study are selected and received more recommended medications and invasive strategies. However, this management is not associated with a lower mortality at one-year.

Funding Acknowledgement

Type of funding source: None
Premature acute coronary syndrome
Authors: Menezes Fernandes R , Mota T , Bispo J.S , Azevedo P.M , Bento D , Guedes J , Carvalho D , Marques N , Santos W , Mimoso J , Jesus I
Published: November 2020

Introduction

The prevalence of acute coronary syndrome (ACS) at an early age is rising, resulting in higher morbidity and mortality rates.

Purpose

To characterize patients admitted with premature ACS, comparing with those with non-premature ACS.

Methods

A retrospective study encompassing patients of a National Registry of ACS was performed. We compared two groups: one composed of men <55 and women <65 years-old; and other with men ≥55 and women ≥65 years-old at the ACS admission. Clinical characteristics, in-hospital evolution and 1-year clinical outcomes were analysed. Primary endpoint was the composite of in-hospital mortality, stroke and re-myocardial infarction (MI). Secondary endpoints were re-MI, stroke, in-hospital and 1-year mortality, 1-year cardiovascular (CV) and non-CV readmissions.

Results

A total of 26523 patients were enrolled and 6637 (25%) had premature ACS, with a mean age of 49±7 years-old. It was found a larger prevalence of smoking habits, obesity and dyslipidemia, but not diabetes. ST-segment elevation MI (STEMI) was the main admission diagnosis (51,2% vs 40,3%), with more frequent activations of the STEMI network (17,1% vs 12,8%) and a consequently shorter time from symptom onset to admission (483 vs 584 min). Coronary angiogram was largely performed in younger patients (91,4% vs 82,1%), mainly revealing one-vessel disease (49,3% vs 34,3%). They had lower Killip-Kimbal (KK) class (6% vs 18,1% with KK class >1) and mostly preserved left ventricular ejection fraction (LVEF) (67,3% vs 58,6%). Major bleeding (0,9% vs 1,7%), sustained ventricular tachycardia (1,1% vs 1,5%) and mechanical complications (0,2% vs 0,7%) were uncommon. Composite endpoint was more frequent in non-premature ACS patients (6,2% vs 1,9%). Non-premature age, KK class >1, multivessel disease and depressed LVEF were independent predictors of primary endpoint (each with p<0,001). Younger patients had inferior rates of in-hospital mortality (1% vs 4,7%), re-MI (0,5% vs 1%) and stroke (0,4% vs 0,7%). One-year mortality (1,7% vs 9,1%), and 1-year CV (9,7% vs 15,5%) and non-CV readmissions (3,7% vs 8,2%) were also lower. All comparative data presented have a statistically significant p-value (p<0,012).

Conclusions

Premature ACS affects 25% of the ACS population, mostly presenting with STEMI, but generally associated with better clinical evolution. Nevertheless, primary prevention is essential to correct modifiable CV risk factors and reduce coronary events in these patients.

Funding Acknowledgement

Type of funding source: None
Evaluation of clinical features and metrics of care in women with st-elevation myocardial infarction treated in a pharmaco-invasive strategy network
Authors: Melo E.S , Veloso P.M , Terencio A.S , Souza J.G , Batista E.P , Fragoso A.O.S , Moritz M.A , Gioia L.N , Coelho G.M.M , Galhardo A , Souza J.M.A , Moraes P.I.M , Goncalves Jr I , Barbosa A.H.P , Caixeta A.M
Published: November 2020

Introduction

Despite worse cardiovascular outcomes, including higher mortality, reported in women with acute myocardial infarction, it is uncertain whether these differences can be explained by a discordant risk profile between genders.

Objective

To compare clinical data and metrics of care between women and men diagnosed with ST elevation myocardial infarction (STEMI).

Methods

We analyzed 2723 consecutive STEMI patients, of whom 29.8% (811) were women, treated in a regional network from March-2010 to December-2019, first seen in primary hospitals, where they received fibrinolysis (96% tenecteplase), and then systematically transferred to a tertiary center for cardiac catheterization (pharmaco-invasive strategy). Categorical variables were compared using chi-square test and numerical variables expressed as median and interquartile range and compared using Mann-Whitney test. A binary logistic regression model was developed to determine whether female gender was an independent predictor of mortality.

Results

Compared to men, women were older (60 [53–69] x 56 [49–63] years; p<0.01), had more hypertension (68.9% x 56.5%; p<0.01), diabetes (36.6% x 28.3%; p<0.01), hypothyroidism (12.0% x 3.3%; p<0.01), kidney failure with an estimated creatinine clearance <60 mL/min (24.7% x 15.4%; p<0.01) and higher baseline LDL-cholesterol (128 [107–160] x 124 [100–154] mg / dL; p=0.03). Smoking (65.2% x 58.2%; p<0.01) and alcoholism (16.1% x 3.1%; p<0.01) were more frequent in men. Regarding the metrics of care, women had longer times from symptoms onset to first medical contact (120 [60–240] x 115 [60–210] minutes; p=0.02) and longer pain-to-needle median times (69 [42–120] x 72 [49–120] minutes; p=0.03). There was no difference between genders regarding percentage of failure reperfusion after lytic, median time from fibrinolysis to cardiac catheterization, maximum troponin values and days of hospitalization. Women had higher unadjusted in-hospital mortality (8.0% x 4.8%; p<0.01). However, after adjusting for confounding variables in the multivariate regression model, the female gender was not an independent predictor of death (odds ratio 1.17 with a 95% confidence interval of 0.69–1.80).

Conclusion

After adjusting for risk variables, female gender was not related to higher in-hospital mortality in STEMI patients treated with pharmaco-invasive strategy. However, women had a higher cardiovascular risk profile compared to men and worse metrics of care, including greater delay in reperfusion therapy.

Funding Acknowledgement

Type of funding source: None
Aggressive lipid lowering therapy with pitavastatin and ezetimibe improve cardiovascular outcomes in patients with ST segment elevation myocardial infarction: insights from the HIJ-PROPER Study
Authors: Otsuki H , Arashi H , Nakazawa M , Inagaki Y , Ebihara S , Tanaka K , Nakao M , Watanabe E , Ogawa H , Yamaguchi J , Hagiwara N
Published: November 2020

Aims

The purpose of this study was to evaluate the effect of aggressive lipid-lowering therapy with pitavastatin and ezetimibe in patients with ST-segment elevation myocardial infarction (STEMI) as compared with those with other classification of an acute coronary syndrome (ACS) including non-STEMI (NSTEMI) and unstable angina pectoris (UA).

Methods

This is a post hoc sub-analysis of the HIJ-PROPER study. In the original study, ACS patients with dyslipidemia were randomized to either pitavastatin + ezetimibe therapy or pitavastatin monotherapy. In the present analysis, we divided HIJ-PROPER participants into the STEMI group (n=880) and NSTEMI + UA group (n=841). Cardiovascular events were analyzed between the two groups. The primary endpoint was a composite of major advanced cardiovascular events (MACE; all-cause death, non-fatal myocardial infarction, non-fatal stroke, unstable angina pectoris, and ischemia-driven revascularization)

Result

During median follow-up period of 3.4 years, the cumulative incidence of the primary endpoint in STEMI group was 31.9% in the pitavastatin+ezetimibe therapy, compared with 39.7% in the pitavastatin-monotherapy (HR, 0.77; 95% CI, 0.62–0.97; p=0.02). However, there was no effect of pitavastatin+ezetimibe therapy on the primary endpoint in the NSTEMI + UA group. Concerning the individual components of the primary endpoint in STEMI group, the percentage of occurrence of all-cause death was significantly lower in the pitavastatin+ezetimibe therapy compared to pitavastatin mono-therapy (14 patients (3.2%) vs. 31 patients (6.9%), respectively; HR, 0.45; 95% CI, 0.23–1.84, p=0.01). Multivariate analysis revealed that use of ezetimibe and prevalence of diabetes mellitus at baseline were independent predictors of primary endpoints in STEMI group (HR, 0.79; 95% CI, 0.63–0.99; p=0.04 for use of ezetimibe, HR 1.54; 95% CI, 1.22–1.94, p=0.0003 for diabetes mellitus).

Conclusion

Patients with pitavastatin+ezetimibe therapy as compared with pitavastatin-monotherapy had lower cardiovascular event in patients with ST-segment elevation myocardial infarction.

Kaplan-Meier curves for primary endpoint

Funding Acknowledgement

Type of funding source: None
Prognostic impacts of prehospital age shock index in patients with acute myocardial infarction
Authors: Hirota Y , Moriwaki K , Takasaki A , Takamura T , Kurita T , Fujii E , Saito Y , Yamada N , Ito M , Dohi K
Published: November 2020

Introduction

Early identification of high-risk patients is the cornerstone of managing patients with acute myocardial infarction (AMI). Age Shock index (ASI; age multiplied by the ratio of heart rate/systolic blood pressure) has been reported to be similar to Global Registry of Acute Coronary Events (GRACE) risk score for predicting mortality in patients with AMI. However, prognostic impacts of prehospital ASI (pre-ASI) in patients with AMI remain unknown.

Methods

We analyzed of 2578 AMI patients who underwent emergency primary percutaneous coronary intervention (PCI) from January 2013 to March 2018, using data from Mie ACS Registry, a prospective and multicenter registry in Japan. Pre-ASI was recorded by emergency medical services at the first contact with the patient before admission, and in-hospital ASI (in-ASI) was recorded prior to PCI at admission. The primary end point was defined as all-cause death.

Results

Median follow-up duration was 753 days (497–838 days). All-cause death was observed in 230 (8.9%) patients. The ROC-AUC (Receiver operating characteristic-area under the curve) of pre-ASI for all- cause death was 0.76 (p<0.001), which was similar to that of in-ASI (0.78, p<0.001) (p=0.25 for pre-ASI versus in-ASI). The cut-off value for pre-ASI and in-ASI was for the prediction of all-cause death was both 45 with a sensitivity of 0.66 and a specificity of 0.78, with a sensitivity of 0.68 and a specificity of 0.76 respectively. According to the Kaplan-Meier survival analysis by combination of pre-ASI≥45 and in-ASI≥45, the patients with pre-ASI≥45 and in-ASI≥45 showed significantly higher all-cause mortality compared to the patients with pre-ASI≥45 and in-ASI<45, the patients with pre-ASI<45 and in-ASI≥45, and the patients with pre-ASI<45 and in-ASI<45 (p<0.001) (Figure). The addition of pre-ASI≥45 to in-ASI≥45 (global chi-squared score: 205) resulted in a significantly increased global chi-squared score, suggesting the incremental prognostic value of pre-ASI (267; p<0.001). Multivariate cox proportional hazard regression analysis for all-cause mortality demonstrated pre-ASI≥45 was a significant independent predictor (HR: 4.86; 95% CI: 3.36 to 7.02, p<0.001). It was strongest predictor compared to left ventricular ejection fraction<40% (HR: 2.45; 95% CI 1.67 to 3.58, p<0.001), hemodialysis (HR: 3.45; 95% CI 1.66 to 7.17, p=0.001), door to balloon time>90 minutes (HR: 1.66; 95% CI 1.18 to 2.34, p=0.004).

Conclusions

High pre-ASI predict increase mortality and assessment of both high pre-ASI and high in-ASI enhance risk stratification in patients with AMI. Early recognizing high pre-ASI may help us make better strategies and improve prognosis for high-risk AMI patients.

Figure 1

Funding Acknowledgement

Type of funding source: None
Outcomes in patients with acute myocardial infarction and a history of illicit drug use: a nationwide analysis
Authors: Genet T , Ma I , Bisson A , Bodin A , Herbert J , Ivanes F , Babuty D , Angoulvant D , Fauchier L
Published: November 2020

Background

Several reports suggest that illicit drug use may be a major cause of acute myocardial infarction (AMI) independently of smoking habits, and associated with a poorer prognosis.

Purpose

We sought to determine the frequency of history of illicit drug use in an AMI population and its impact on short- and mid-term prognosis.

Methods

Based on the administrative hospital-discharge database, we collected information for all patients treated with AMI between 2010 and 2018 in France. We identified patients with history of illicit drug use and the adverse outcomes were investigated during follow-up.

Results

Among 797,212 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI (mean age 69 years, 66% male), 3827 patients (0.5%) had a known history of illicit drug use (cannabis, cocaine or opioid). Patients with illicit drug use were younger and had less comorbidities. They presented more frequently with STEMI and anterior localization compared to those with no history of illicit drug use. In univariate analysis, patients with illicit drug use had lower short-term mortality rates compared to those without history of illicit drug use: 4.9% vs 10.1% at one month (p<0.0001), respectively. However, this might be attributed to a younger age at the time of presentation. Using logistic multivariable analysis with adjustment on age, gender, other cardiovascular and non-cardiovascular comorbidities, type and localisation of MI and procedures of revascularization, history of illicit drug use was associated with a non-significant higher risk of death at one year (adjusted odds ratio OR 1.12 95% CI 0.98–1.29). This trend was supported by a significantly higher risk of death at one year in patients with a history of opioid use (OR 1.27 95% CI 1.04–1.29, p=0.01).

Conclusion

In a large and systematic nationwide analysis of patients with AMI, history of illicit drug use was associated with a non-significant higher overall odds of mortality, which was significant among those with opioid use.

Funding Acknowledgement

Type of funding source: None
Soluble urokinase plasminogen activator receptor (suPAR) predicts 2-year cardiovascular events in patients after acute chest pain
Authors: Chew-Harris J , Appleby S , Troughton R.W , Richards A.M , Pemberton C.J
Published: November 2020

Background

Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker of sub-inflammation related to plaque instability. Its modulation may reflect on immune dysfunction related to cardiovascular (CVD) outcomes. We assessed the prognostic performance of suPAR to predict 2-year clinical outcomes in patients with acute chest pain, suspicious of acute coronary syndromes.

Methods

A total of 812 patients presenting to the emergency department with the primary complaint of acute chest pain were prospectively recruited. Baseline suPAR concentrations were measured at presentation using the ViroGates CE-marked ELISA. Standard cardiac markers including hsTnT and NT-proBNP (both Roche) were also measured. Data for all biomarkers were treated as continuous and expressed as median [interquartile range (IQR)]. Statistical assessment was made using SPSS v25 (IBM). Groups were compared by Mann-Whitney U test/Spearman's rho. Prognostic performance of suPAR in comparison with hsTnT and NT-proBNP to predict the primary outcomes of new myocardial infarction (MI), new heart failure (HF), all cause readmission, and the composite of major adverse cardiac events (MACE) were assessed using binary logistic regression after the adjustment of traditional risk factors.

Results

In the entire chest pain cohort [median age: 63 yrs (IQR: 54–74), 34% female], 156/812 of patients had adjudicated AMI [STEMI (n=22)/NSTEMI (n=134)]. suPAR concentrations were found to be lower in males (Spearman's Rho, r=−0.17, P<0.0001) and in those with eGFR ≥60mL/min/1.73m2 (n=439) (r=−0.40, P<0.0001), but elevated in those older than 65 years (n=372) (r=0.55, P<0.0001). During the 2-year follow-up period, there were 54 fatalities, 287 recorded as having new CVD events, 46 diagnosed with new heart failure, 71 with new MI (66 NSTEMI/5 STEMI), 54 with new unstable angina, 126 patients classified with MACE and 190 patients who were readmitted into hospital within 1-year from presentation. In logistic regression analyses, the odds ratio (OR) of suPAR; 8.5 (95% CI:1.8–40.9) to predict a 2-year event (for example new total CVD events) was stronger than hsTnT; OR: 1.2 (95% CI: 0.9–1.5) and NT-proBNP; OR: 0.8 (95% CI:0.8–1.3) (P<0.0001) (Figure). Further, incorporation of baseline suPAR values into multivariate models for predicting events, such as MACE at 2-years (adjusted for age, gender and eGFR), resulted in an improvement in the C-statistic from 0.72 to 0.76.

Conclusion

In this acute chest pain cohort, suPAR concentrations are independent predictors of cardiovascular outcomes at 2 years. suPAR may add value in the risk assessment of patients with acute chest pain.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Health Research Council of New Zealand, National Heart Foundation of New Zealand