Angiographic predictors of aberrant circumflex artery during cardiac catheterization.

OBJECTIVES: To identify angiographic predictors of aberrant left circumflex artery (LCx) by comparing left main (LM) length and bifurcation angle between patients with aberrant LCx and normal anatomy. BACKGROUND: Failure to recognize aberrant LCx during a cardiac catheterization may hamper correct diagnosis, delay intervention in acute coronary syndromes, and result in increased contrast volume, radiation exposure, and infarct size. METHODS: We retrospectively analyzed angiograms of aberrant LCx patients and normal anatomy matched controls, in three-participating centers. LM-length, bifurcation angle between the left anterior descending (LAD) and the first non-LAD branch of the LM, and procedural data were compared. RESULTS: Between 2003 and 2020, 136 patients with aberrant LCx and 135 controls were identified. More catheters (2.4 ± 0.6 vs. 2.2 ± 0.9, p = 0.009), larger contrast volumes (169 ± 94 ml vs. 129 ± 68 ml, p < 0.0005), and prolonged fluoroscopy time (652.9 ± 623.7 s vs. 393.1 ± 332.1 s, p < 0.0005), were required in the aberrant LCx-group compared with controls. Patients with aberrant LCx had a longer LM-length and a more acute bifurcation angle, both in caudal and cranial views, compared with controls (24.7 ± 8.1 vs. 10.8 ± 4.5 mm, p < 0.0005 and 26.7 ± 7.4 vs. 12 ± 5.5 mm, p < 0.0005, respectively, and 45.2° ± 12° vs. 88.8° ± 23°, p < 0.0005 and 51.9° ± 21° vs. 68.2° ± 28.3°, p < 0.0005, respectively). In ROC analysis, LM-length showed the best diagnostic accuracy for detecting aberrant LCx. In multiple logistic regression analysis, a cranially measured LM-length > 17.7 mm was associated with a 5.3 times greater probability of predicting aberrant LCx [95% CI (3.4-8.1), p < 0.0001]. CONCLUSIONS: Our study suggests that a long LM-length and an acute bifurcation angle can indicate the presence of aberrant LCx. We present a practical algorithm for its rapid identification.

Heat Shock Protein 70 Is Associated With Cardioversion Outcome and Recurrence of Symptomatic Recent Onset Atrial Fibrillation in Hypertensive Patients.

ABSTRACT: Accumulating evidence indicates that heat shock proteins (HSPs) may represent a suitable biomarker to predict atrial fibrillation (AF). We investigated the relation of circulating serum HSP70 (sHSP70) with inflammatory cytokines and recurrence of symptomatic recent onset AF (ROAF). We enrolled 90 patients with ROAF (the duration from onset of symptoms ≤24 hours) and 30 controls. Patients received amiodarone for cardioversion and rhythm control. The association of serum HSP70, serum interleukin-2 (sIL-2), and serum interleukin-4 (sIL-4) with the presence of cardioversion and AF recurrence within a year was investigated. Toll-like receptor 4 (TLR4) signaling dependence for IL-2 and IL-4 induction in response to stimulation with HSP70 was tested in rat aortic vascular smooth muscle cell cultures. Patients had higher sHSP70 and sIL-2 and lower sIL-4 compared with controls. Serum HSP70 was independently associated with ROAF (P = 0.005) and correlated with sIL-2 (r = 0.494, P < 0.001) and sIL-4 (r = -0.550, P < 0.001). By 48 hours, 71 of the 90 patients were cardioverted, with noncardioverted patients having higher sHSP70 and sIL-2 and lower sIL-4, which were the only independent factors associated with cardioversion. AF recurred in 38 of the 71 cardioverted patients in 1 year. A cutoff value of sHSP70 ≥0.65 ng/mL and sIL-2 ≥0.21 pg/mL was the only independent factor associated with AF recurrence (hazard ratio: 3.311, 95% confidence interval: 1.503-7.293, P = 0.003 and hazard ratio: 3.144, 95% confidence interval: 1.341-7.374, P = 0.008, respectively). The exposure of smooth muscle cell to HSP70 in vitro increased the expression of IL-2 (5×) and IL-4 (1.5×) through TLR4-dependent and receptor-independent mechanisms. In conclusion, sHSP70 and sIL-2 might constitute a prognostic tool for determining the cardioversion and recurrence likelihood in ROAF.

Cytoprotective Mechanisms of DJ-1: Implications in Cardiac Pathophysiology.

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson's disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1's role as a plausible novel therapeutic target for cardiovascular disease.

Circulating Ligands of the Receptor for Advanced Glycation End Products and the Soluble Form of the Receptor Modulate Cardiovascular Cell Apoptosis in Diabetes.

We determined whether plasma concentrations of the receptor for advanced glycation end products (RAGE) and the soluble (s) form of RAGE (sRAGE) in healthy individuals and patients with type 2 diabetes (T2D) modulate vascular remodeling. Healthy individuals and patients with T2D were divided into two age groups: young = <35 years old or middle-aged (36-64 years old) and stratified based on normal glucose tolerance (NGT), impaired (IGT), and T2D. Plasma titers of sRAGE, the RAGE ligands, AGEs, S100B, S100A1, S100A6, and the apoptotic marker Fas ligand Fas(L) were measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic potential of the above RAGE ligands and sRAGE were assessed in cultured adult rat aortic smooth muscle cells (ASMC). In NGT individuals, aging increased the circulating levels of AGEs and S100B and decreased sRAGE, S100A1 and S100A6. Middle-aged patients with T2D presented higher levels of circulating S100B, AGEs and FasL, but lower levels of sRAGE, S100A1 and S100A6 than individuals with NGT or IGT. Treatment of ASMC with either AGEs or S100B at concentrations detected in T2D patients increased markers of inflammation and apoptosis. Responses attenuated by concomitant administration of sRAGE. In middle-aged patients with T2D, lower circulating plasma levels of sRAGE may limit decoy and exogenous trapping of deleterious pro-apoptotic/pro-inflammatory RAGE ligands AGEs and S100B, increasing the risk for diabetic complications.

Major adverse cardiovascular events while awaiting staged non-culprit percutaneous coronary intervention after ST-segment elevation myocardial infarction.

BACKGROUND: The optimal therapeutic strategy for ST-segment elevation myocardial infarction (STEMI) patients found to have multi-vessel disease (MVD) is controversial but recent data support complete revascularisation (CR). Whether CR should be completed during the index admission or during a second staged admission remains unclear. Our main objective was to measure rates of major adverse cardiovascular events (MACEs) during the waiting period in STEMI patients selected for staged revascularisation (SR), in order to determine the safety of delaying CR. For completeness, we also describe 30-day and long-term outcomes in STEMI patients with MVD who underwent in-hospital CR. METHODS: A single-centre retrospective analysis of 931 STEMI patients treated by primary percutaneous coronary intervention (PCI) identified 397 patients with MVD who were haemodynamically stable and presented within 12 hours of chest pain onset. Of these, 191 underwent multi-vessel PCI: 49 during the index admission and 142 patients undergoing a strategy of SR. RESULTS: Our main finding was that waiting period MACE were 2% (three of 142) in patients allocated to SR (at a median of 31 days). In patients allocated to in-hospital CR, 30-day MACE rates were 10% (five of 49). During a median follow up of 39 months, all-cause mortality was 7.0% vs. 28.6%, and cardiac mortality was 2% vs. 8%, in patients allocated to SR or CR, respectively. CONCLUSIONS: Patients with STEMI and MVD who, based on clinical judgement, were allocated to a second admission SR strategy had very few adverse events during the waiting period and excellent long-term outcomes.

Long-term survival and preprocedural predictors of mortality in high surgical risk patients undergoing percutaneous mitral valve repair.

OBJECTIVES: To evaluate long-term survival in high surgical risk patients undergoing percutaneous mitral valve repair (MVR) using the MitraClip(®) system and to identify preprocedural predictors of long-term mortality. BACKGROUND: Data for long-term survival and preprocedural predictors of mortality after percutaneous MVR in high surgical risk patients are sporadic. METHODS: From January 2009 to April 2013, 136 consecutive high surgical risk patients, with symptomatic moderate-to-severe or severe mitral regurgitation (MR), underwent percutaneous MVR using the MitraClip system. Cardiac and overall survival was determined at one and 2 years postprocedure. Univariate and multivariate analysis was performed to identify preprocedural predictors of long-term mortality. RESULTS: One year postprocedure, cardiac and overall survival was 86.7% and 84.6%, respectively and at 2 years cardiac and overall survival was 77.7% and 74.8%, respectively. In univariate analysis advanced age, lower body mass index, impaired renal function, elevated levels of log-N-terminal-pro-brain-natriuretic-peptide (log-NTproBNP), poor performance in functional tests (New York Heart Association (NYHA) class) and high logistic Euroscore (LES) and Society of Thoracic Surgeons (STS) score were identified as preprocedural predictors of long-term cardiac mortality. In multivariate analysis preoperative NYHA class III and IV, elevated levels of log-NTproBNP and advanced age predicted long-term cardiac mortality. CONCLUSIONS: Percutaneous MVR using the MitraClip system has favorable long-term survival rates in high surgical risk patients. Preprocedural NYHA functional class III and IV, elevated log-NTproBNP levels and advanced age predict higher long-term cardiac mortality and should be considered during patient selection.

Churg-Strauss syndrome masquerading as an acute coronary syndrome.

Churg-Strauss Syndrome (CSS) is a rare vasculitis with multiorgan involvement. Cardiac manifestations are common causing serious complications. We report a case of CSS masquerading as a non-ST elevation myocardial infarction with heart failure. CSS should be considered in the differential diagnosis of an acute coronary syndrome(ACS)with normal coronary arteries when history of asthma, peripheral eosinophilia and multisystemic involvement is present.

Coronary angiography through the interosseous artery: expanding the limits of the wrist approach.

A 59-year-old diabetic man with a history of numerous coronary angiographies (CAs) and peripheral artery disease underwent CA due to a non-ST elevation myocardial infarction. Femoral, radial, and ulnar arteries were unpalpable.

Coronary artery ectasia and inflammatory cytokines: link with a predominant Th-2 immune response?

OBJECTIVE: The role of inflammation in coronary artery ectasia (CAE) remains controversial. We evaluated the hypothesis that CAE might be associated with a specific pattern of T helper (Th) lymphocyte activation by measuring the Th-1 cytokine, interleukin-2 (IL-2) and the Th-2 cytokines, interleukin-4 (IL-4) and interleukin-6 (IL-6) in patients with CAE, obstructive coronary artery disease (CAD) and controls. METHODS: Serum levels of IL-2, IL-4 and IL-6 were measured in 74 patients undergoing an elective cardiac catheterization due to angina pectoris and positive or equivocal non-invasive screening for cardiac ischaemia: 34 had CAE and non-obstructive CAD (Group A), 22 had obstructive CAD (Group B) and 18 had normal coronaries (Group C). RESULTS: Group A had significantly higher IL-4 than Group B and Group C (p<0.001 and p=0.006, respectively). In contrast, Group A had markedly lower IL-2 than Group B and Group C (p<0.001 for both comparisons). Group C had higher IL-4 and lower IL-2 than Group B (p<0.001 for both comparisons). Interleukin-6 was significantly higher in Groups A and B compared to Group C (p<0.001 for both comparisons), whilst it was comparable between Group A and Group B. Multivariate logistic regression analysis showed that higher levels of IL-4 and lower levels of IL-2 were the strongest independent predictors associated with CAE (OR: 3.846, CI: 1.677-8.822, p=0.001 and OR: 0.567, CI: 0.387-0.831, p=0.004, respectively). CONCLUSIONS: Our data demonstrates that Th-2 immune response, exhibited through increased IL-4 and low IL-2, constitutes a fundamental feature of CAE.

Emerging markers of inflammation and oxidative stress as potential predictors of coronary artery disease.

BACKGROUND AND AIMS: The multi-ligand receptor for advanced glycation end products (RAGE) and its ligands AGEs and S100/calgranulin proteins are important mediators of inflammation and oxidative stress whereas the soluble form of RAGE (sRAGE) by acting as a decoy and the antioxidant PARK7/DJ-1 exert antiatherogenic effects. We examined whether sRAGE and its ligands AGEs, S100A8/A9, S100B, S100A12 and DJ-1 are associated with the presence of angiographic coronary artery disease (CAD) in asymptomatic patients with and without diabetes. METHODS AND RESULTS: Plasma levels of RAGE ligands, sRAGE and DJ-1 were determined in 50 patients with angiographically proven CAD and in 50 age-matched healthy controls. In the whole cohort, lower levels of sRAGE and higher levels of interleukin-6 (IL-6), the RAGE ligands S100B, S100A12 and the AGEs/sRAGE ratio were associated with CAD. In patients without diabetes (n = 72), lower levels of sRAGE and DJ-1 and higher levels of IL-6 and AGEs/sRAGE ratio were associated with CAD. In multivariable analysis, AGEs/sRAGE ratio was an independent predictor of CAD both in the whole cohort (p = 0.034, OR = 1.247, [95%CI: 1.024, 1.0519]) and in the subgroup of patients without diabetes (p = 0.021, OR = 1.363, 95%CI [1.048, 1.771]) on top of established cardiovascular risk factors. CONCLUSION: Alterations in plasma RAGE axis inflammatory mediators are associated with atherosclerosis, and higher levels of AGEs/sRAGE ratio are independently associated with CAD in asymptomatic patients and may act as a novel biomarker for predicting CAD. DJ-1 emerges as promising marker of oxidative stress in CAD patients without diabetes, a finding that deserves further study.

Emergent Inflammatory Markers and Echocardiographic Indices in Patients with Bronchial Asthma.

Asthma is a heterogeneous disease, characterized by chronic inflammation and oxidative stress of the airways. Several inflammatory pathways including activation of the receptor for advanced glycation end products (RAGE) have been described in the course of the disease. DJ-1 is a redox-sensitive protein with multifaceted roles in mast cell homeostasis and an emerging role in the pathogenesis of asthma. Moreover, cardiac function abnormalities have been described via echocardiography in patients with asthma. The main aim of this study was to investigate the plasma levels of RAGE, its ligands and DJ-1 in asthmatic patients pre- and post-treatment along with echocardiographic indices of cardiovascular function. The study population was divided into two groups. Group A included 13 patients with newly diagnosed bronchial asthma who were free of treatment for at least two weeks and Group B included 12 patients without asthma. An echocardiography examination was performed on all patients. The plasma levels of RAGE, its ligands (AGEs, S100A12, S100B, S100A8/A9), the interleukins (IL-6, IL-1ß) and DJ-1 were measured. No differences were noted among the two groups for baseline characteristics and echocardiographic indices of cardiac function. In Group A, 31% suffered from mild asthma, 54% from moderate asthma and 15% from severe asthma. Plasma levels of IL-6, AGEs and AGE/RAGE ratio were increased and those of S100A12 and DJ-1 were decreased in asthmatics. Pharmacotherapy with corticosteroids/ß2-agonists decreased IL-6, and AGEs, and increased DJ-1. In search of novel approaches in diagnosing and treating patients with asthma, S100A12, ratio AGE/sRAGE, and DJ-1 in addition to IL-6 may prove to be useful tools.

The role of intravascular imaging in chronic total occlusion percutaneous coronary intervention.

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Differential Expression of Circulating Damage-Associated Molecular Patterns in Patients with Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is defined as abnormal dilation of a coronary artery with a diameter exceeding that of adjacent normal arterial segment by >1.5 times. CAE is a pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE frequently coexists with coronary artery disease (CAD). While inflammation appears to be involved, the pathophysiology of CAE remains unclear. Damage-associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue, are deemed as alarm signals by the innate immune system. Inflammatory agents can generate DAMPs and DAMPs can create a pro-inflammatory state. In a prospective cross-sectional study, we enrolled 29 patients with CAE and non-obstructive CAD, 19 patients with obstructive CAD without CAE, and 14 control subjects with normal (control) coronary arteries age- and sex-matched with the CAE patients, to investigate the differential expression of plasma DAMPs. Patients with CAE and non-obstructive CAD had increased plasma levels of the DAMPs S100B, S100A12, HMGB1, and HSP70, the DAMPs receptor TLR4, and miR328a-3p compared to CAD and controls. Plasma levels of the mir328a-3p target the protective soluble form of the DAMPs receptor for advanced glycation end products (sRAGE), and the antioxidant DJ-1 was decreased in both CAE and CAD compared to controls. In an in vitro human umbilical vein endothelial cells model, circulating levels of S100B, HMGB1, HSP70 as well as CAE patient plasma induced inflammatory responses. The differential expression of the DAMPs S100B, HSP70, HMGB1, and their receptors TLR4 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.

Summarising data and factors associated with COVID-19 related conspiracy theories in the first year of the pandemic: a systematic review and narrative synthesis.

Conspiracy theories can have particularly harmful effects by negatively shaping health-related behaviours. A significant number of COVID-19 specific conspiracy theories emerged in the immediate aftermath of the pandemic outbreak. The aim of this study was to systematically review the literature on conspiracy theories related to COVID-19 during the first year of the pandemic (2020), to identify their prevalence, their determinants and their public health consequences. A comprehensive literature search was carried out in PubMed and PsycINFO to detect all studies examining any conspiracy theory related to COVID-19 between January 1st 2020, and January 10th 2021. Forty-three studies were included with a total of 61,809 participants. Between 0.4 and 82.7% of participants agreed with at least one conspiracy belief. Certain sociodemographic factors (young age, female gender, being non-white, lower socioeconomic status), psychological aspects (pessimism, blaming others, anger) and other qualities (political conservatism, religiosity, mistrust in science and using social media as source of information) were associated with increased acceptance of conspiracy theories. Conspiracy beliefs led to harmful health-related behaviours and posed a serious public health threat. Large-scale collaborations between governments and healthcare organizations are needed to curb the spread of conspiracy theories and their adverse consequences.