bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation and role of arginine vasopressin in myocardial infarction/reperfusion
Authors: Andre N , Spyridopoulos I
Published: November 2020

Background

Little attention is paid to the coronary microvasculature when treating acute myocardial infarction (MI). Microvascular obstruction contributes to ischaemia-reperfusion (I-R) injury. One proposed mechanism is a persistent vasoconstrictor tone during MI/reperfusion. Arginine vasopressin (AVP) has a vasoactive effect on the coronary microvessels. Moreover, cardiac AVP synthesis was found in an animal model. To exert vasoconstriction, AVP binds to its receptor 1a (AVPR1a).

Aims

(i) To analyse the AVP levels during MI/reperfusion (ii) To assess cardiac AVP and AVPR1a expressions in MI/reperfusion mouse models.

Methods

We took arterial blood samples from ST elevation MI (STEMI) patients admitted to our hospital over the course of MI/reperfusion for AVP levels quantification. We also measured AVP through its more stable surrogate biomarker, copeptin. Cardiac MRI was done to evaluate coronary microvasculature, infarct size, and left ventricular ejection fraction (LVEF) 1 week post-admission. Cardiac AVP and AVPR1a expressions were assessed by polymerase chain reaction (PCR) in mouse models.

Results

STEMI patients displayed bothAVPand copeptinlevels elevation at baseline (130.8±20.5 pmol/l, n=23) until 90 min post-reperfusion (55.7±6.2 pmol/l, n=23). Their concentrations began to approach normal levels at 24h. Patients with poorer reperfusion outcomes had copeptin concentrations that remained above normal level after 24h following reperfusion. Copeptin levels at 24h post-reperfusion were significantly higher in patients who developed larger infarct size (p=0.004) and lower LVEF (p=0.009). Patients with microvascular obstruction tended to have higher copeptin levels from admission until 24h post-reperfusion. Mouse models showed no cardiac AVP expression but significantly high AVPR1a expression at 2h post-reperfusion.

Conclusion

In STEMI patients, circulating AVP level is elevated over the course of MI/reperfusion. In MI/reperfusion mouse models, cardiac AVP synthesis is absent but cardiac AVPR1a is upregulated. The combination of delayed decline in AVP concentrations and AVPR1a upregulation may increase the possibility for AVP to mediate I-R injury through microvascular disturbance. Increased AVP levels at 24h post-reperfusion are significantly associated with poor reperfusion outcome. These results warrant further studies concerning the use of AVP receptor antagonist in STEMI patients undergoing reperfusion therapy

Copeptin levels and reperfusion outcomes

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Newcastle University MRes Programme
Genetic factors and the presence of coronary collaterals in patients with stable coronary artery disease
Authors: Kozlova E , Starostin I , Balatskyi A , Bulkina O , Lopukhova V , Karpov U
Published: November 2020

Background

The coronary collateral circulation (CCC) varies in patients with coronary artery disease (CAD). Although many studies were provided to detect factors associated with collateral development, genetic factors are still studied insufficiently. The goal of this study was to assess the association of single nucleotide polymorphisms (SNP) in genes involved in vascular growth with CCC in patients with stable CAD.

Purpose

To assess if genetic variations in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), urokinase-type plasminogen activator (gene PLAU) are associated with the presence of coronary collaterals in patients with stable CAD.

Methods

A single-centered study was performed between March 2012 and December 2017. In 579 patients with stable CAD who underwent coronary angiography and had at least 50% stenosis in at least one major coronary artery collaterals were assessed by the use of the Rentrop score (0–3) during coronary angiography. SNPs PLAU rs4065, VEGF rs1570360, rs2010963 and rs699947, HGF rs5745752 were genotyped, multivariate logistic regression was carried out to determine the association of genotypes with CCC.

Results

337 patients had visible coronary collaterals (Rentrop grade 1, 2 and 3) and 236 patients didn't have visible collaterals (Rentrop grade 0). Beside traditional risk factors of poor CCC - diabetes, smoking and arterial hypertension – patients without visible coronary collaterals (Rentrop 0) showed a higher frequency of the HGF rs5745752 CC genotype than those with visible coronary collaterals (Rentrop 1–3; p=0.001). (Fig. 1) The odds ratio of having CCC Rentrop 0 in patients with genotype CC was statistically significant (odds ratio = 1.94 [95% confidence interval: 1.38–2.76]; p=0.001). Statistical analysis showed that the PLAU rs4065 and VEGF rs1570360, rs2010963 and rs699947 polymorphisms were not associated with CCC (p<0.05).

Conclusion

An association was found between the HGF rs5745752 polymorphism and the CCC in patients with stable CAD. Patients with the CC genotype are at greater risk of developing poor coronary collaterals.

Figure 1

Funding Acknowledgement

Type of funding source: None
Myocardial energetic efficiency is depressed in ischemia with non-obstructive coronary arteries
Authors: Eskerud I , Mancusi C , Khan I , Berge C.A , Larsen T , Lonnebakken M.T
Published: November 2020

Background

Ischemia with non-obstructive coronary arteries (INOCA) is incompletely understood. Depressed myocardial energetic efficiency index (MEEi), the ratio between external work and myocardial oxygen consumption, has been shown in heart failure. However, MEEi in INOCA has not been explored.

Purpose

To test whether MEEi is associated with INOCA.

Methods

We included 125 patients (56% women, age 62±9 years) with exercise-induced chest pain and non-obstructive coronary arteries (stenosis <50%) by coronary computed tomography angiography (CCTA). Stroke volume (SV) and left ventricular (LV) mass were assessed by echocardiography. MEEi was calculated as (systolic blood pressure (SBP) x SV) / (SBP x heart rate) and normalized for LV mass. LV hypertrophy was defined as LV mass index >46.7 g/m2.7 in women and >49.2 g/m2.7 in men. Myocardial ischemia was detected by myocardial contrast stress echocardiography. Coronary artery plaque burden was measured as plaque volume by CCTA.

Results

In univariable regression analysis, stress-induced ischemia, male sex, diabetes, hypertension, LV hypertrophy, lower LV ejection fraction and higher SBP were associated with MEEi (all p<0.05). There were no associations with age, obesity or coronary artery plaque burden. MEEi was lower in patients with stress-induced ischemia (n=66) compared to patients without ischemia (0.47±0.16 vs. 0.54±0.21 ml/sec x g–1, p=0.026). In multivariable linear regression analysis, MEEi remained associated with stress-induced myocardial ischemia after adjustment for cardiovascular risk factors, SBP, LV hypertrophy, LV ejection fraction and coronary artery plaque burden (R2 0.26, p<0.001, Table).

Conclusion

MEEi is depressed in patients with INOCA. Our results suggest that myocardial ischemia negatively influences MEEi in patients with non-obstructive coronary arteries.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Western Norway Regional Health Authority, University of Bergen
Inflammatory associated microRNAs expression in cardiomyocytes and blood serum in CAD patients
Authors: Polyakova E , Zaraiskii M , Baranova E , Shlyakhto E
Published: November 2020

Objective

To evaluate inflammatory associated microRNAs: miRNA-27a, miRNA-133a and miRNA-203 expression in CAD patients and to explore whether tissue expression is correlated with serum miRNA expression.

Methods

This cross-sectional observational study comprised 100 subjects (mean age 60.9±1.0 years old; 67% men). The left atrial and blood serum expression of the miRNA-27a, miRNA-133a and miR-203 was analyzed using real-time PCR in. 80 patients referred for CABG surgery (40 of them with multi-vessel CAD) and 20 control patients undergoing heart valve surgery. Patients with CAD did not have a history of myocardial infarction, they were patients with stable chronic CAD with planned coronary arteries bypass graft surgery (CABG).

Results

The levels of miRNA-27a, miRNA-133a and miRNA-203 myocardial and serum expression in patients with clinically relevant three-vessel coronary stenosis were significantly higher than in patients with 1–2 vessel disease, and significantly higher in both CAD cohorts compared to subjects without coronary atherosclerosis. The myocardial expression of miRNA-27a and miRNA-133a was significantly higher than serum expression, while miRNA-203 myocardial expression was lower serum expression. Serum miRNA-203 expression displayed the greatest differences between compared groups. Decision tree method established that the risk of atherosclerotic heart disease increases five-fold if miRNA-203 serum expression was more than 101.00 REU (OR 5.9 & CI 94.21–107.93).

Conclusions

Myocardial miRNA-27a, miRNA-133a and miRNA-203 expression in the left atrium and blood serum is higher in CAD patients than in non-CAD subjects, and the expression level is strongly associated with the number of affected coronary vessels. Although larger studies are required to confirm our findings, our results suggest that serum miRNA-203 expression level is correlated with myocardial tissue expression, severity of coronary atherosclerosis and might be proposed as a marker of the CAD extent.

Funding Acknowledgement

Type of funding source: None
Cocaine use and HIV-infection modify coronary plaque morphology differently than conventional cardiovascular risk factors
Authors: Kolossvary M , Bluemke D.A , Fishman E.K , Gerstenblith G , Mandler R.N , Kickler T.S , Chen S , Bhatia S , Lai S , Lai H
Published: November 2020

Background/Introduction

Cardiovascular risk factors are assumed to propagate coronary artery disease (CAD) through the lipid and/or inflammatory pathologic pathways. However, we currently do not have any in-vivo information whether these effects may alter CAD morphology and structure differently.

Purpose

We wished to assess whether conventional cardiovascular risk factors (which are assumed to affect CAD primarily through the lipid pathway), and unconventional risk factors such as cocaine use and human immunodeficiency virus (HIV)-infection (which are assumed to propagate CAD primarily through the inflammatory pathway) affect different coronary plaque structures as assessed by radiomics.

Methods

In our prospective longitudinal observational study of 300 individuals without cardiovascular symptoms but with coronary CT angiography (CCTA)-confirmed atherosclerosis (210 male, age: 48±7 years) of whom 161 were cocaine users at baseline with or without HIV-infection (226 HIV-infected), underwent CCTA at two time points (mean follow-up: 4.0±2.3 years). Precision phenotyping of CAD was done by calculating 1276 radiomic features on the 861 plaques. Linear mixed models corrected for plaque volume, high-sensitivity C-reactive protein, statin use and positive family history were used to assess the effects of chronic cocaine use, HIV-infection and elevated atherosclerotic cardiovascular disease risk (ASCVD≥7.5%). Hierarchical clustering was used to assess potential clusters among significant radiomic features. Bonferroni corrected p<0.00004 (0.05/1276) was considered significant.

Results

Overall, 32.0% (409/1276) of the radiomic features showed any significant association, of which 74.1% (303/409), 4.2% (17/409) and 25.4% (104/409) were affected by cocaine use, HIV-infection and elevated ASCVD risk, respectively. There was no overlap among radiomic features significantly associated with increased ASCVD risk and cocaine use or HIV-infection, while 88,2% (15/17) of HIV-infection associated parameters were also affected by cocaine use. Cluster analysis indicated 13 different structural components among significant features, of which eight were unique to chronic cocaine use, three unique to ASCVD risk, and two contained parameters associated with chronic cocaine use, elevated ASCVD risk and/or HIV-infection.

Interpretation

Chronic cocaine use and HIV-infection modify different CAD morphological components than conventional cardiovascular risk factors, potentially implying independent pathological pathways of disease progression irrespective of each other.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health, National Institute on Drug Abuse
Serial evaluation of cardiac allograft vasculopathy after heart transplantation by dual-modality intravascular ultrasound and optical coherence tomography
Authors: Shiraki T , Ohtani T , Kioka H , Mizote I , Tsukamoto Y , Nakamura D , Yokoi K , Ide S , Nakamoto K , Takeda Y , Hikoso S , Sawa Y , Sakata Y
Published: November 2020

Background

Cardiac allograft vasculopathy is a combination of the development of de novo plaque and the progression of donor-transmitted plaque.

Purpose

This study aimed to evaluate the development of de novo plaque and the progression of donor-transmitted plaque within 12-month after heart transplantation (HTx) using serial intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The association between inflammatory cytokines and plaque progression was also examined.

Methods

We prospectively enrolled 40 recipients to conduct serial three-vessel IVUS and OCT analysis at 8-week and 12-month after HTx. De novo plaque was defined as having maximum intimal thickness (MIT) ≥0.5 mm at 12-month in the absence of donor-transmitted plaques (MIT ≥0.5 mm at 8-week). Serum cytokines were screened with a bead-based multiplex assay.

Results

A total of 13 de novo plaques (fibrous, n=10; fibroatheroma, n=3) were detected in eight recipients. Serum interleukin (IL)-31 at 8-week was associated with the development of de novo plaques (p=0.009). A total of 31 donor-transmitted plaques (fibrous, n=12; fibroatheroma, n=11; fibrocalcific, n=8) were detected in 17 recipients. Multiple regression analysis revealed that fibrous (p=0.026) and fibroatheroma (p=0.012) observed at 8-week were significantly associated with subsequent plaque progression within 12-month after HTx. ΔPlaque burden was significant higher in de novo plaque than donor-transmitted plaque (38.8% [29.6–41.2] versus 8.7% [1.3–13.6], p<0.001). The prevalence of macrophage accumulation was lower in de novo plaque than in donor-transmitted plaque (8% versus 52%, p=0.006). Serum IL-31 at 8-week was correlated with the progression of donor-transmitted plaque as well as de novo plaque (r=0.663, p=0.029) although other cytokines like IL-1β, IL-6, IL-17, and tissue necrotic factor alpha were not.

Conclusions

In de novo plaques, fibrous plaque was the most common and macrophage accumulation was rarely observed. In donor-transmitted plaque, fibrous and fibroatheroma were independent predictor for the subsequent plaque progression. Serum interleukin-31 surge at subacute phase may play pathogenic role in cardiac allograft vasculopathy.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grants-in-Aid for Scientific Research (KAKENHI)
Circulating immune cell profiles detected by mass cytometry differ significantly between patients with predominantly calcified and predominantly non-calcified coronary atherosclerosis
Authors: Kott K.A , Hansen T , De Dreu M , Vernon S.T , Kim T , Yang J.J , Fazekas De St Groth B , McGuire H , Figtree G.A
Published: November 2020

Background/Introduction

Inflammation is now a well-established component of the pathophysiology of coronary artery disease (CAD), but it is unknown whether atherosclerosis is associated with a distinct circulating immune cell profile. Mass cytometry time-of-flight (CYTOF) is a new precision technology which can be used to assess leukocyte populations comprehensively.

Purpose

To determine if patients with calcified and non-calcified (soft) coronary plaque have distinct circulating immune cell profiles when compared to healthy controls, and to assess whether this could be used to detect sub-clinical CAD.

Methods

Patients referred for a CT coronary angiogram were recruited; blood samples were collected and peripheral blood mononuclear cells (PBMCs) were isolated. Imaging data was analysed using a modified Gensini scoring system which incorporated plaque composition, with higher weighting given to soft plaque. The modified Gensini scores were then used to further segregate into calcified-predominant and soft-predominant disease groups. CYTOF analysis was performed on the PBMCs, with groups as outlined in Table 1.

Results

Age was significantly higher in the CAD+ group, but all other demographic features and risk factors did not differ between groups. Patients with predominantly calcified disease showed an increase in memory CD8 T cells (p=0.004), an increase in CD 39+ CD4 T cells (p=0.028), and a decrease in naïve CD8 T cells (p=0.005), which suggests an accumulated memory response in more quiescent disease. Patients with predominantly soft-plaque disease have higher pro-inflammatory monocyte populations (p=0.013) and proliferative CD4 T cell populations (p=0.011), suggesting acute innate and adaptive responses to biologically active plaque.

Conclusions

This pilot study has shown that further study should be pursued into the utility of CYTOF to identify sub-clinical CAD through differences in peripheral circulating immune cell profiles.

Figure 1

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): National Health and Medical Research Council of Australia, Heart Research Australia
Greater coronary lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound in patients with elevated xanthine oxidoreductase: a mechanistic insight
Authors: Saito Y , Mori N , Saito K , Matsuoka T , Tateishi K , Kitahara H , Fujimoto Y , Kobayashi Y
Published: November 2020

Background

Elevated serum uric acid level was reportedly associated with greater coronary lipid plaque. Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in purine metabolism and believed to play important roles in coronary atherosclerosis. However, the relation of XOR to coronary lipid plaque and its mechanism are unclear.

Purpose

The aim of this study was to assess the impact of XOR on coronary lipid plaque and the associated factors with XOR in coronary artery disease (CAD).

Methods

Patients with stable CAD undergoing elective percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were prospectively enrolled. They were divided into three groups according to serum XOR activities; low, normal, and high. Coronary lipid core plaques in non-target vessels were evaluated by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). Systemic endothelial function and inflammation were assessed with reactive hyperemia index (RHI) and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio.

Results

Of 68 patients, 26, 31, and 11 were classified as low, normal, and high XOR activity groups. LCBI (474.4±171.6 vs. 347.4±181.6 vs. 294.0±155.9, p=0.04) and maxLCBI4mm (102.1±56.5 vs. 65.6±48.5 vs. 55.6±37.8, p=0.04) were significantly higher in high XOR group than in normal and low XOR groups. Although RHI was significantly correlated with body mass index, diabetes, current smoking, and high-density lipoprotein cholesterol, no relation was found between XOR activity and RHI (Figure). There were also no relations between XOR activity and high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, or platelet-to-lymphocyte ratio (Figure).

Conclusion

Elevated XOR activity was associated with greater coronary lipid plaque in patients with stable CAD, without significant relations to systemic endothelial function and inflammation.

Funding Acknowledgement

Type of funding source: None
Association of sleep duration and cardiovascular events
Authors: Wang W.T , Huang C.C , Hsu P.F , Lin C.C , Wang Y.J , Din Y.Z , Liou T.L , Wang Y.W , Huang S.S , Lu T.M , Chan W.L , Leu H.B
Published: November 2020

Background/Purpose

Sleep duration have been associated with cardiovascular (CV) risk in general population. Nevertheless, their impact in real-world large cohort data remains unclear.

Methods

4861 healthy Taiwanese subjects (mean age 68 years, 3535 males, 72.7%) were enrolled. Three groups were defined: short sleep duration <6 h, reference sleep duration 7 to 8 h, and long sleep duration >8h. Multivariate Cox proportional hazard models were used to examine the associations between sleep duration and major adverse cardiovascular events (MACE), composite of acute myocardial infarction, ischemic stroke, and CV death.

Results

Sleep duration of short, reference, and long were reported by 37.7%, 30.3%, 32.0% of the cohort, respectively. 165 (3.4%), 502 (10.3%), 108 (2.2%) suffered from CV death, MACE, ischemic stroke, respectively. After adjusting for age, sex, systolic blood pressure, diabetes, body mass index, low density lipoprotein, and numbers of involved coronary artery, only long sleep was associated with higher MACE (hazard ratio (HR): 1.317, 95% confidence interval (CI): [1.052 to 1.648], p value = 0.016), ischemic stroke (HR: 1.858, 95% CI: [1.162 to 2.969], p value = 0.010), and lower rate of MACE plus heart failure (HR: 1.228, 95% CI: [1.034 to 1.459], p value = 0.019).

Conclusions

Our study addressed long sleep duration was independently associated with higher rate of MACE, ischemic stroke and MACE plus heart failure in adult Chinese population in Taiwan.

Funding Acknowledgement

Type of funding source: None
HbA1C modified Clinical SYNTAX score as a prognostic tool in patients with diabetes mellitus and multi-vessel coronary artery disease treated with primary percutaneous coronary intervention
Authors: Ruzicic D , Mirkovic M.M
Published: November 2020

Introduction

Patients with acute coronary syndrome (ACS) and diabetes mellitus (DM) have an increased risk of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI), which is not estimated sufficiently-multidimensionally in terms of type and severity of the ACS and/or DM and angiographic findings.

Aim

The study was intended to estimate and compare the predictive clinical value of the modified SYNTAX score versus the predictive clinical value of the SYNTAX score to the one-year appearance of MACE after conducted PCI in patients with DM (with diagnosis longer than one year and multivessel disease) and acute coronary syndrome (ACS).

Material and methods

A prospective cross-section study was performed in patients with DM and ACS. In the PCI period the following risk factors where were recorded: 1) age and metabolic variables – glycosylated hemoglobin (HbA1c), total cholesterol, triglyceridemia; 2) endocrinological variables – DM therapy, tip of DM; 3) ACS modality; 4) radiological / anatomical variable – SYNTAX score and 5) clinical variables in modified ACEF score and clinical SYNTAX score. One-year MACE were recorded.

Results

From a total of 136 consecutive patients, 55 of them developed at least one MACE in one-year follow-up. Two highly predictable MACE risk indexes (MACERI) were constructed. The first risk index – MACERI (c statistic = 0.879) was defined by: SYNTAX score >21, modified ACEF >1.38, HbA1c ≥8 (%), triglyceridemia ≥2.3 (mmol / L) in patients on insulin therapy and ACS modality – unstable angina pectoris. MACERI has better predictive characteristics than SYNTAX score (c statistic = 0.798) as well as ACF score, but not in relation to clinical SYNTAX score (c statistic = 0.820). The second risk index – MACERI II (c statistic = 0.923), defined the same risk factors as MACERI, except HbA1c ≥8 (%),which additionally contains a risk factor – the presence of three-vessel disease. MACERI II had significantly better predictive characteristics than all mentioned scores, but also in relation to MACERI.

Conclusions

MACERI and MACERI II can potentially have great application in future risk factors studies for one-year MACE in patients with DM and ACS who underwent PCI, because with them the effects of these factors measure multidimensionally at valid and accurate manner.

Funding Acknowledgement

Type of funding source: None
Atrial Fibrillation is related with higher in-hospital morality in acute myocardial infarction (AMI) patients from K-ACTIVE registry
Authors: Mori H , Maeda A , Akashi Y , Ako J , Ikari Y , Ebina T , Sato N , Tamura K , Namiki A , Fukui K , Michishita I , Kimura K , Suzuki H
Published: November 2020

Background

The prognostic significance of atrial fibrillation (AF) on in-hospital mortality in acute myocardial infarction (AMI) patients is not fully understood in Japanese patients.

Methods

To elucidate the clinical significance of AF on in-hospital mortality in AMI patients, we analyzed the Japanese observational prospective multicenter registry of acute myocardial infarction (K-ACTIVE: Kanagawa ACuTe cardio Vacular rEgistry), which spans October 2016 to December 2019.

Results

A total of 3482 patients included 336 patients with AF and 3146 patients with sinus rhythm. Table 1 shows patient baseline characteristics. Patients with AF were significantly older than those with sinus rhythm (75 vs 67, P<0.0001). Prevalence of hypertension and hemodialysis were significantly greater in patients with AF than patients with sinus rhythm while prevalence of dyslipidemia and smoking were significantly less in patients with AF than patients with sinus rhythm. Table 2 shows characteristics of AMI. There were no significant difference in prevalence of STEMI, area of MI, Peak CK/CK-MB and prevalence of multivessel disease. However, patients with AF showed lower systolic blood pressure, faster heart rate, worse Killip category, greater prevalence of OHCA. Need of mechanical support including IABP/ECMO were greater in patients with AF than patients with sinus rhythm. In-hospital mortality was significantly higher in patients with AF than in patients with sinus rhythm (Figure, 10.4% versus 5.2%, P=0.0005). This trend didn't change even after adjustment with age and sex (Odds ratio 1.6 95% confidence interval 1.1–2.4, P=0.02).

Conclusion

AF was associated with higher in-hospital mortality in Japanese AMI patients.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by JSPS KAKENHI Grant Number JP15K09101.
Diabetes is not a risk factor for myocardial infarction in patients without coronary artery disease
Authors: Gyldenkerne C , Olesen K.K.W , Thrane P.G , Madsen M , Thim T , Wurtz M , Jensen L.O , Raungaard B , Poulsen P.L , Boetker H.E , Maeng M
Published: November 2020

Background

Diabetes is considered a risk factor for myocardial infarction (MI). However, we have previously found that diabetes was not a short-term risk factor for MI in the absence of obstructive coronary artery disease (CAD).

Purpose

As long-term data are not available, we aimed to assess adverse cardiac events in patients with and without diabetes stratified by CAD up to 11 years after coronary angiography.

Methods

We conducted a cohort study of patients undergoing coronary angiography from 2003 to 2012 and followed them by cross-linking Danish health registries. Patients were stratified according to the presence/absence of CAD and diabetes. Outcomes included MI, cardiac death, all-cause death, and coronary revascularization.

Results

A total of 86,202 patients were included (diabetes: n=12,652). Median follow-up was 8.8 years. Using patients with neither CAD nor diabetes as reference (cumulative MI incidence 2.6%), the risk of MI was similar for patients with diabetes alone (3.2%; hazard ratio 1.202, 95% CI: 0.996–1.451), was increased for patients with CAD alone (9.3%; hazard ratio 2.75, 95% CI: 2.52–3.01), and was highest for patients with both CAD and diabetes (12.3%; hazard ratio 3.79, 95% CI: 3.43–4.20), see Figure. Similar associations were observed for cardiac death and coronary revascularization.

Conclusions

Diabetes patients without CAD by coronary angiography have a similar risk of MI compared to patients with neither CAD nor diabetes. In the presence of CAD, however, diabetes increases the risk of MI.

Figure 1

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Clinical impact of triglyceride deposit cardiomyovasculopathy, coronary atherosclerosis with triglyceride deposition, on vascular failure after drug-eluting stent implantation
Authors: Nakano Y , Onishi T , Suzuki M , Niwa T , Mukai K , Ando H , Ohashi H , Waseda K , Takashima H , Amano T
Published: November 2020

Background

Triglyceride deposit cardiomyovasculopathy (TGCV) is a novel cardiovascular disorder, encoded as orphan disease in Europe in 2019, characterized by excessive accumulation of triglyceride in vascular smooth muscle cells, leading to coronary artery disease (CAD). However, there is no data about impact of TGCV on vascular failure after coronary stent implantation.

Purpose

To assess impact of TGCV on the outcome following coronary stent implantation in CAD patients with diabetes mellitus (DM) as Study 1, and chronic hemodialysis as Study 2.

Methods

This is multicenter retrospective estimation consisting of two studies.

Study 1) Among 526 consecutive patients suspected of having CAD who underwent coronary angiography (CAG) and iodine-123-β-methyliodophenyl-pentadecanoic acid (BMIPP) scintigraphy, a tracer for the diagnosis of TGCV, data from 81 patients with DM were analyzed.

The patients were divided into two groups; TGCV (n=7) or non-TGCV (n=74). All patients were implanted with a second-generation DES and underwent follow-up CAG. Binary restenosis (ISR), defined as angiographic luminal diameter >50% by quantitative coronary angiography, in-stent late loss were assessed in 15 stents of TGCV patients and 111 stents of non-TGCV patients.

Study 2) Similarly, among 88 chronic hemodialysis patients, ISR and in-stent late loss were assessed in 12 stents of 9 TGCV patients and 21 stents of 17 non-TGCV patients.

Results

Study 1) There were no significant differences in baseline characteristics between the two groups. In-stent late loss was greater in TGCV group than in non-TGCV group (0.91mm [0.27, 2.39] vs. 0.15mm [0.03, 0.35]; p<0.001), resulting in greater incidence of ISR in TGCV group than in non-TGCV group (46.7% vs. 9.0%; p<0.001). Multivariable logistic analysis revealed TGCV to be an independent predictor for vascular failure after DES implantation in patients with DM.

Study 2) Similarly, in-stent late loss and incidence of ISR were greater in TGCV group than in non-TGCV group (1.20±0.99mm vs. 0.50±0.70, p=0.02; 58.3% vs. 9.5%, p=0.002, respectively). TGCV was an independent predictor for vascular failure after DES implantation in chronic hemodialysis patients.

Conclusion

Apart from existing risk factors such as DM and hemodialysis, TGCV could contribute to a novel risk factor for vascular failure, even in the second-generation DES era.

Figure 1

Funding Acknowledgement

Type of funding source: None
Prevalence of type 2 diabetes with stable coronary artery disease but without prior myocardial infarction or stroke and THEMIS-like patients from the SNDS French nationwide claims database
Authors: Blin P , Darmon P , Henry P , Dureau-Pournin C , Bernard M.-A , Guiard E , Maizi H , Thomas-Delecourt F , Lassalle R , Droz-Perroteau C , Moore N
Published: November 2020

Background

The THEMIS randomized controlled trial showed that patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), without prior myocardial infarction (MI) or stroke, and who received ticagrelor plus aspirin, had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. The number of patients concerned and their characteristics in current practice are not well known.

Purpose

To assess the characteristics of CAD-T2DM adults (≥18 years) without prior MI-stroke, and more specifically, of THEMIS-like patients in a real world setting.

Methods

Cohort within the main scheme of the SNDS (Système National des Données de Santé), the French nationwide claims database, representing about 86% of 66 million people. All CAD-T2DM prevalent patients without prior MI-stroke were identified on January 1st, 2014 (index date) based on a 5-year database history, and followed for two years. The THEMIS-like population included CAD-T2DM patients without prior MI-stroke ≥50 years at index date without renal failure with dialysis, cirrhosis or liver cancer history, as well as no intracranial and gastro-intestinal bleeding for the last 6 months, or anticoagulant or antiplatelet agent 2 months before and after index date. Study prevalence was standardized for the European population for 1,000 adults (‰) using sex and 5-year age classes from Eurostat statistics.

Results

From the 359,595 CAD-T2DM patients identified in the database, 71.8% had no prior MI-stroke (n=258,260), including 24.9% of THEMIS-like patients (n=64,334). CAD-T2DM without prior MI-stroke and THEMIS-like patients had the same mean age of 72 years, with 68% and 66% men, 26% and 25% with more than 4-year CAD and T2DM history, 79% and 76% of hypertension, 28% and 19% of revascularisation procedure, 19% and 11% of peripheral arterial disease, 16% and 9% of heart failure, and 39% and 32% of diabetes complications, respectively. The table below presents prevalence estimation per 1,000 European adults with differences according to both populations, as well as sex and age-classes.

Conclusions

The two populations had similar characteristics, although noting some differences in comorbidities. The THEMIS-like prevalence was estimated to 1.50‰ European adults, representing about a quarter of CAD-T2DM patients without prior MI-stroke.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Study performed with unconditional funding from AstraZeneca
The impact of gender on outcomes in patients with chronic total coronary occlusions undergoing percutaneous coronary intervention: results from a Dutch nationwide registry including 7560 patients
Authors: Van Veelen A , Elias J , Van Dongen I.M , Henriques J.P.S , Knaapen P
Published: November 2020

Background

Females comprise a minority of patients with chronic total occlusions (CTO). It is known that men have a greater benefit from CTO percutaneous coronary intervention (PCI) than women. We aimed to determine gender-based differences in baseline characteristics and outcomes after PCI in patients with CTO.

Methods

The Netherlands Heart Registration (NHR) is a nationwide registry that registers outcomes of cardiac interventions. For the purpose of this analysis, the data of all patients undergoing PCI from inception of the NHR to December 2018 were selected, that included PCI with at least one CTO in one of the treated coronary arteries. We compared baseline characteristics and the outcomes 1 year mortality, 30 day myocardial infarction (MI) and target vessel revascularization (TVR) <1 year between men and women.

Results

A total of 7560 patients were identified that underwent PCI between January 1, 2015 and December 31, 2018 with at least 1 CTO in the treated vessel. A total of 5850 was male (77.4%) and 1710 was female (22.6%). Women were older (68.5±10.6 versus 64.7±10.6 years old, p<0.001), and more frequently had diabetes (29.4% [n=529] versus 25.0% [n=1602], p<0.001) and kidney disease (4.5% [n=529] versus 2.2% [n=142], p<0.001). However, men had more extensive cardiovascular disease, i.e. multi-vessel disease (56.0% [n=3584] versus 50.4% [n=912], p<0.001), previous MI (39.7% [n=2527] versus 31.0% [n=555], p<0.001), previous PCI (48.2% [n=1967] versus 40.2% [n=455], p<0.001) and previous coronary artery bypass grafting (16.8% [n=1085] versus 10.5% [n=191], p<0.001) and more frequently presented with an out-of-hospital cardiac arrest, compared to women (2.1% [n=136] versus 1.1% [n=20], p=0.004). The 1-year mortality was higher in women (10.3% versus 7.5%, p<0.001), as well as the 30-day MI (0.9% versus 0.4%, p=0.043), but men had higher risk for TVR<1 year (11.7% versus 9.5%, p=0.044). Corrected for age and comorbidities, female gender was an independent predictor for mortality (Figure 1; odds ratio 1.83, 95% confidence interval 1.08–3.11, p=0.025).

Conclusion

In this nationwide registry comprising 7560 CTO patients undergoing PCI, significant gender-based differences were found. Males were found to have more extensive cardiovascular disease. However, females were at higher risk of mortality, possibly due to higher age and higher prevalence of concomitant comorbidities.

Figure 1. Survival curve

Funding Acknowledgement

Type of funding source: None
What troponin I level post PCI in SIHD is predictive of higher risk of MACE?
Authors: Moosavi V , Ebrahimi R , Yang Q , Harvey T , Das S.K , Ariarathna N , Tran Q , Marley P , Farshid A
Published: November 2020

Background

According to the 4th universal definition of myocardial infarction (MI), post percutaneous coronary intervention (PCI) MI is defined as an elevation of cardiac troponin values more than five times above the 99th percentile upper reference limit. The ISCHEMIA Trial in stable ischaemic heart disease (SIHD) patients reported post PCI troponin rise as part of the primary endpoint. What represents a clinically significant troponin rise post PCI has not been clearly established.

Purpose

The aim of our study was to correlate the level of troponin I rise with adverse events post PCI in SIHD.

Methods

We performed a retrospective analysis of our PCI registry in patients with SIHD between 2014 and 2018. Patients with acute coronary syndrome were excluded. HS-troponin I was measured one day after the procedure. The primary end point was major adverse cardiac events (MACE) including death, MI, stent thrombosis (ST) and need for repeat revascularization within 12 months from index procedure.

Results

Between 2014 and 2018, 920 patients (mean age 67.5 years, 78% male) underwent PCI for SIHD. Troponin rise post PCI was a common event and a level more than 100ng/L (reference range <26 ng/L) occurred in 54% of patients. Mean and median troponin I level post PCI was 675 ng/L±2530 and 118 ng/L respectively. In patients with MACE, mean troponin I level was 1361 ng/L compared with 611 ng/L in patients without MACE (P=0.0176). Correlation of troponin I level with one year MACE rates are shown in the Graph. MACE rates were steady at 8.5% with troponin I levels below 2500 ng/L after which there was a significant increase in the MACE rates. At troponin I level above 5000 ng/L MACE was 13.6% and above 10,000 ng/L it was 33.3%.

Conclusion

Troponin I levels above 2500 ng/L (x100 upper limit normal) correlated with an increase in the risk of MACE in patients undergoing PCI for SIHD. Our results suggest that current definitions of procedural MI overestimate the clinical significance of post PCI troponin rise.

Funding Acknowledgement

Type of funding source: None
Younger patients have an increased risk for dementia after coronary artery bypass grafting, a population-based cohort study from the SWEDEHEART registry
Authors: Nielsen S , Giang K.W , Karlsson M , Hansson E.C , Pivodic A , Lindgren M , Jeppsson A
Published: November 2020

Background

Previous studies investigating the association between coronary artery bypass grafting (CABG) and risk for dementia show conflicting results.

Purpose

To compare the long-term risk for dementia in CABG patients to matched individuals in the general population, and to identify independent predictors for developing dementia after CABG.

Methods

Data from the SWEDEHEART registry and three other mandatory national registries were merged to compare all patients who underwent isolated CABG in Sweden from 1992 to 2015 (n=111.335) with an age- and sex-matched control individuals from the general population (n=222.396). Cumulative incidence adjusted for the competing risk for death and Cox regression models with Hazard Ratio (HR) and 95% confidence interval (CI) adjusted for age, gender, co-morbidity and socioeconomic variables, were used to calculate the risk of dementia. Median follow-up was 10.1 years (IQR 2.5–14.7) among CABG patients and 10.7 years (5.6–15.7) among the controls. Identified interactions of the excess risk for dementia with sex and age categories (<65, 65-<75, ≥75 years) resulted in analyses being stratified on those sub-cohorts.

Results

The overall cumulative incidence at 20 years follow up of all-cause dementia was 9.6% (95% CI 9.4–9.9) among CABG patients and 9.0 (8.8–9.2) among individuals in the general population. The adjusted relative risk for all-cause dementia was increased among CABG patients <65 years and 65–75 years, (HR 1.29 (95% CI 1.17–1.41) and HR 1.06 (1.01–1.11), respectively (fig 1). The risk for all-cause dementia was higher in CABG women than in CABG men (HR 1.62 (1.30–2.03) vs HR 1.22 (1.10–1.35)). In the oldest age group (75 years and older) the risk for all cause dementia, vascular dementia and Alzheimer's disease was lower for CABG patients compared to controls (HR 0.73 (0.69–0.78). Female CABG patients <65 years had an increased risk for Alzheimer's disease (HR 1.83 (1.06–3.15). Hypertension, diabetes, preoperative stroke, renal failure, heart failure, atrial fibrillation, depression and low income were independent predictors for all-cause dementia in CABG patients.

Conclusion

CABG patients younger than 75 years at the time of surgery have an increased risk of all-cause dementia compared to an age- and sex-matched population. Women younger than 65 years that underwent CABG had also a markedly higher risk for Alzheimer disease. Increased awareness of the higher risk for dementia in younger CABG patients is warranted to avoid delay of diagnosis and treatment.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Swedish Heart and Lung Foundation, Swedish State
Outcomes of 7560 chronic total occlusion patients undergoing percutaneous coronary intervention: results from a Dutch nationwide registry
Authors: Van Veelen A , Elias J , Van Dongen I.M , Henriques J.P.S , Knaapen P
Published: November 2020

Background

The presence of a chronic total coronary occlusion (CTO) is associated with worse clinical outcomes. We aimed to identify CTO patients that are at risk of these outcomes in a nationwide registry.

Methods

The Netherlands Heart Registration (NHR) is a nationwide registry that registers outcomes of cardiac interventions. For the purpose of this analysis, the data of all patients undergoing PCI from inception of the NHR to December 2019 were selected, that included PCI with at least one CTO in one of the treated coronary arteries. We used multivariate logistic regression of baseline characteristics for the outcome measures target vessel revascularization (TVR) <1 year, 30-day myocardial infarction (MI) and 1-year mortality. The impact of the assessed risk factors on outcomes was described as odds ratio (OR) with corresponding 95% confidence intervals (CI).

Results

A total of 7560 patients underwent PCI with ≥1 CTO in one of the treated arteries between January 1, 2015 until December 31, 2018 (mean age 65±10 years, 77.4% male [n=5850]). Five percent of patients deceased within 1 year after PCI (n=375), TVR<1 year occurred in 11% (n=525/4804) and 30-day MI occurred in 0.5% (25/4985). In multivariate regression, the only predictor for TVR<1 year was the presence of diabetes mellitus (OR 1.29, 95% CI 1.06–1.56). Predictors for the outcome MI <30 days were female gender (OR 2.24, 95% CI 1.05–4.79), chronic kidney disease (OR 3.94, 95% CI 1.15–13.50) and cardiogenic shock at presentation (OR 7.94, 95% CI 2.28–27.7). Strong predictors for 1 year mortality were the presence of cardiogenic shock at presentation (OR 17.86, 95% CI 2.90–109.92) and the presence of chronic kidney disease (OR 4.56, 95% CI 2.04–10.16), other predictors were age (OR 1.04, 95% CI 1.01–1.07), female gender (OR 1.83, 95% CI 1.08–3.10), diabetes (OR 1.66, 95% CI 1.01–2.73) and left ventricular ejection fraction (LVEF; OR 0.95, 95% CI 0.93–0.97).

Conclusion

In this nationwide registry of 7560 CTO patients undergoing PCI, cardiogenic shock and chronic kidney disease were strong predictors for 1 year mortality and 30 day MI. Diabetes mellitus was the only predictor for the occurrence of TVR <1 year. Identification of patients at risk for poor clinical outcomes may help improve the outcomes of CTO patients in the future.

Funding Acknowledgement

Type of funding source: None
Circulating secretoneurin concentrations are increased in patients with acute coronary syndrome and provide prognostic information
Authors: Myhre P , Ottesen A.H , Faaren A.L , Tveit S.H , Springett J , Pyylampi J , Stridsberg M , Christensen G , Omland T , Rosjo H
Published: November 2020

Background

Secretoneurin (SN) is associated with both myocardial ischemia and cardiomyocyte Ca2+ handling, and circulating SN levels provide incremental prognostic information to established risk indices in patients with acute heart failure, acute respiratory failure, and after cardiac arrest.

Purpose

To determine whether SN concentrations are increased in patients with acute coronary syndrome (ACS), and assess the prognostic value of SN among patients with suspected ACS.

Methods

We included 402 patients hospitalized with chest pain at a teaching hospital and adjudicated all hospitalizations as ACS or non-ACS by two physicians working independently. Blood samples were drawn within 24 h from hospital admission and SN was measured by a novel ELISA assay. Patients were followed for mean 6.2 years and mortality was obtained from the Norwegian Cause of Death Registry.

Results

SN concentrations were higher in patients with ACS (n=161 [40%]) compared to patients with chest pain without ACS (n=241 [60%]): median 32.8 (IQR 27.5–42.8) vs. 28 (24.5–34.0) pmol/L, p<0.001. The C-statistics of SN was 0.66 (95% CI: 0.61–0.71) to separate chest pain patients with ACS from chest pain patients without ACS compared to 0.82 (0.78–0.86) for high-sensitivity cardiac troponin T (hs-cTnT). Patients with ECG changes reflective of acute myocardial ischemia had higher SN concentrations (p=0.005). Sixty-five (16%) patients died during follow-up. Stratifying patients according to SN concentrations separated patients with a poor and favorable prognosis, and patients with SN in the top quartile had 4-fold higher risk of mortality compared to the patients with low SN concentrations (Figure). Higher SN concentrations were also associated with increased risk of mortality in Cox regression models, including in models that adjusted for age, sex, blood pressure, previous myocardial infarction, atrial fibrillation, and heart failure: hazard ratio 1.71 (1.03–2.84), p=0.038. The C-statistics of SN to separate patients with poor prognosis from favorable prognosis was 0.72 (0.65–0.79) and adding SN on top of hs-cTnT improved prognostication as assessed by the integrated discrimination index: 0.05±0.014, p<0.001.

Conclusions

SN concentrations are increased in patients with ACS and provide prognostic information in patients with chest pain.

Figure 1

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): Akershus Unviersity Hospital, CardiNor AS