Immunity and inflammation in cardiovascular disorders.

Recent studies have developed our understanding of the role of the immune system and inflammation in Cardiovascular Disease (CVD), opening new avenues for risk stratification and therapeutic intervention. However, gaps in our knowledge remain. To address this issue, BMC Cardiovascular Disorders has launched a Collection on "Immunity and Inflammation in Cardiovascular Disorders".

Guiding catheter inner lumen damage during percutaneous coronary intervention.

Guiding catheter damage and body wire intermingling are uncommon complications of standard operational procedures. Optimal application of this device includes replacing the small guiding catheter upon excessive resistance during stent insertion.

Isolated ascending aorta dilatation is associated with increased risk of abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an asymptomatic condition characterized by progressive dilatation of the aorta. The purpose of this study is to identify important 2D-TTE aortic indices associated with AAA as predictive tools for undiagnosed AAA. METHODS: In this retrospective study, we evaluated the size of the ascending aorta in patients without known valvular diseases or hemodynamic compromise as predictive tool for undiagnosed AAA. We studied the tubular ascending aorta of 170 patients by 2-dimensional transthoracic echocardiography (2D-TTE). Patients were further divided into two groups, 70 patients with AAA and 100 patients without AAA with normal imaging results. RESULTS: Dilatation of tubular ascending aorta was measured in patients with AAA compared to the group with absent AAA (37.5 ± 4.8 mm vs. 31.2 ± 3.6 mm, p < 0.001, respectively) and confirmed by computed tomographic (CT) (35.6 ± 5.1 mm vs. 30.8 ± 3.7 mm, p < 0.001, respectively). An increase in tubular ascending aorta size was associated with the presence of AAA by both 2D-TTE and CT (r = 0.40, p < 0.001 and r = 0.37, p < 0.001, respectively). The tubular ascending aorta (D diameter) size of ≥33 mm or ≥ 19 mm/m2 presented with 2-4 times more risk of AAA presence (OR 4.68, CI 2.18-10.25, p = 0.001 or OR 2.63, CI 1.21-5.62, p = 0.02, respectively). In addition, multiple logistic regression analysis identified tubular ascending aorta (OR 1.46, p < 0.001), age (OR 1.09, p = 0.013), gender (OR 0.12, p = 0.002), and LVESD (OR 1.24, p = 0.009) as independent risk factors of AAA presence. CONCLUSIONS: An increased tubular ascending aortic diameter, measured by 2D-TTE, is associated with the presence of AAA. Routine 2D-TTE screening for silent AAA by means of ascending aorta analysis, may appear useful especially in older patients with a dilated tubular ascending aorta (≥33 mm).

Impact in total ischemic time and ST-segment elevation myocardial infarction admissions during COVID-19.

BACKGROUND: Despite the COVID-19 pandemic, cardiovascular disease is still the main cause of death in developed countries. Of these deaths, acute coronary syndromes (ACS) account for a substantial percentage of deaths. Improvement in ACS outcomes, are achieved by reducing the time from symptom onset until reperfusion or total ischemic time (TIT). Nevertheless, due to the overwhelming reality at the beginning of the pandemic, acute coronary syndrome (ACS) care may have been compromised. OBJECTIVES: We evaluated delays in TIT based on the date and timing of admissions in patients with STEMI, by a timeline follow-up form, before and during the current COVID-19 pandemic. METHODS: Between July 2018 and June 2020, two hundred and twelve patients diagnosed with ST-segment elevation myocardial infarction (STEMI) were admitted to our medical center. Upon presentation, cases were assigned a timeline report sheet and each time interval, from onset of symptoms to the catheterization lab, was documented. The information was later evaluated to study potential excessive delays throughout ACS management. RESULTS: Our data evidenced that during the COVID-19 pandemic ACS admissions were reduced by 34.54%, in addition to several in-hospital delays in patient's ACS management including delays in door-to-ECG time (9.43 ± 18.21 vs. 18.41 ± 28.34, p = 0.029), ECG-to-balloon (58.25 ± 22.59 vs. 74.39 ± 50.30, p = 0.004) and door-to-balloon time (57.41 ± 27.52 vs. 69.31 ± 54.14, p = 0.04). CONCLUSIONS: During the pandemic a reduction in ACS admissions occurred in our hospital that accompanied with longer in-hospital TIT due to additional tests, triage, protocols to protect and prevent infection within hospital staff, and maintenance of adequate standards of care. However, door-to-balloon time was maintained under 90 min.

Cardiology on the cutting edge: updates from the European Society of Cardiology (ESC) Congress 2020.

The 2020 annual Congress of the European Society of Cardiology (ESC) was the first ever to be held virtually. Under the spotlight of 'the cutting edge of cardiology', exciting and ground-breaking cardiovascular (CV) science was presented both in basic and clinical research. This commentary summarizes essential updates from ESC 2020-The Digital Experience. Despite the challenges that coronavirus disease 2019 (COVID-19) has posed on the conduct of clinical trials, the ESC Congress launched the results of major studies bringing innovation to the field of general cardiology, cardiac surgery, heart failure, interventional cardiology, and atrial fibrillation. In addition to three new ESC guidelines updates, the first ESC Guidelines on Sports Cardiology and Exercise in Patients with Cardiovascular Disease were presented. As former ESC president, Professor Casadei undoubtedly pointed out the ESC Congress 2020 was a great success. During the ESC 2020 Congress, BMC Cardiovascular Disorders updated to seven journal sections including Arrhythmias and Electrophysiology, CV Surgery, Coronary Artery Disease, Epidemiology and Digital health, Hypertension and Vascular biology, Primary prevention and CV Risk, and Structural Diseases, Heart Failure, and Congenital Disorders. To conclude, an important take-home message for all CV health care professionals engaged in the COVID-19 pandemic is that we must foresee and be prepared to tackle the dramatic, long-term CV complications of COVID-19 patients.

Erratum: Goblet cell carcinoid of the appendix: Two case reports and a review of the literature.

[This corrects the article DOI: 10.3892/mco.2019.1921.].

Statins and PCSK9 inhibitors: A new lipid-lowering therapy.

The clinical benefit of lipid-lowering therapies is to reduce circulating levels of atherogenic particles and to ameliorate the risk of atherosclerotic cardiovascular disease (ASCVD). The completion of two major clinical trials on PCSK9 inhibitors (PCSK9i), the FOURIER and the ODYSSEY outcome trials, has marked the beginning of a new era of lipid-lowering drugs. PCSK9i, evolocumab and alirocumab, are monoclonal antibodies that inactivate the liver proprotein convertase subtilisin kexin 9 (PCSK9). Inhibition of PCSK9 increases the number of low-density lipoprotein (LDL) receptors available leading to a profound reduction in circulating LDL particles. By preventing LDL receptor destruction, PCSK9i as adjunct to statin therapy can reduce LDL-C by 50-60% above that achieved by statin therapy alone. In addition, PCSK9i in combination with high-dose statins may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD. Based on evidence from clinical trials, the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias now include the use of PCSK9i to very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe. However, the cost-effectiveness of PCSK9i therapy is limited to secondary prevention in high-risk patients. This review outlines the main clinical trials leading to a change in the guidelines, clinical practice as well as the future challenges of PCSK9i therapy.

Difference in left atrial appendage remodeling between diabetic and nondiabetic patients with atrial fibrillation.

BACKGROUND: Diabetes mellitus (DM) is a common and increasingly prevalent condition in patients with atrial fibrillation (AFib). The left atrium appendage (LAA), a small outpouch from the LA, is the most common location for thrombus formation in patients with AFib. HYPOTHESIS: In this study, we examined LAA remodeling differences between diabetic and nondiabetic patients with AFib. METHODS: This retrospective study analyzed data from 242 subjects subdivided into two subgroups of 122 with DM (diabetic group) and 120 without DM (nondiabetic group). The study group underwent real-time 3-dimensional transesophageal echocardiography (RT3DTEE) for AFib ablation, cardioversion, or LAA device closure. The LAA dimensions were measured using the "Yosefy rotational 3DTEE method." RESULTS: The RT3DTEE analysis revealed that diabetic patients display larger LAA diameters, D1-lengh (2.09 ± 0.50 vs 1.88 ± 0.54 cm, P = .003), D2-width (1.70 ± 0.48 vs 1.55 ± 0.55 cm, P = .024), D3-depth (2.21 ± 0.75 vs 1.99 ± 0.65 cm, P = .017), larger orifice areas (2.8 ± 1.35 and 2.3 ± 1.49 cm2 , P = .004), and diminished orifice flow velocity (37.3 ± 17.6 and 43.7 ± 19.5 cm/sec, P = .008). CONCLUSIONS: Adverse LAA remodeling in DM patients with AFib is characterized by significantly LAA orifice enlargement and reduced orifice flow velocity. Analysis of LAA geometry and hemodynamics may have clinical implications in thrombotic risk assessment and treatment of DM patients with AFib.

Impact of the Change in ESC Guidelines on Clinical Characteristics and Outcomes of Cardiogenic Shock Patients Receiving IABP Therapy.

BACKGROUND: Intra-aortic balloon pump (IABP) counterpulsation provides mechanical support for patients with cardiogenic shock. The aim of the study is to evaluate the clinical characteristics and outcomes of patients with cardiogenic shock receiving IABP before and after the European Society of Cardiology (ESC) downgraded the use of IABP from a class I to a class IIb in 2012. METHODS: Data was obtained from the Acute Coronary Syndrome Israeli Survey (ACSIS) registry, a prospective observational national survey conducted once every two years. From a total of 15,200 patients with acute coronary syndrome (ACS), 524 patients were identified with acute myocardial infarction (AMI)-complicated with cardiogenic shock. The groups were further subdivided based on whether the IABP was implanted before or after the change in guideline recommendation. RESULTS: The study indicates a 24% reduction in IABP use since 2002. Until 2012, a reduction in clinical outcomes including 7-days, 30-days and in-hospital mortality, was observed in patients with IABP compared to the patients with conventional therapy. Conversely, after the ESC changed the guidelines, the clinical outcomes were not improved by IABP treatment. Additionally, the conventional therapy group presented with higher baseline ejection fraction, received less effective treatment, reperfusion and/or pharmacological therapy than patients with IABP. CONCLUSION: The use of IABP as management for cardiogenic shock has diminished over time since the guidelines were modified. After the change in guidelines, the use of IABP is restricted to high-risk, severely compromised and hemodynamically deteriorated patients hence limiting beneficial outcomes.

Goblet cell carcinoid of the appendix: Two case reports and a review of the literature.

Goblet cell carcinoid or carcinoma (GCC) is a rare tumor found incidentally during routine management of acute appendicitis. GCCs are more aggressive compared with conventional appendiceal tumors but less aggressive compared with adenocarcinomas, and they often present with serosal and mesoappendiceal involvement. We herein report two cases of acute appendicitis in a 45-year-old female and a 60-year-old male with varied clinical symptoms. Pathological examination of the appendix revealed the presence of adenocarcinoma with goblet cells and a Ki-67 index of 25% (grade 3) and 15% (grade 2), respectively. Subsequent right hemicolectomy was performed according to the current guidelines. No signs of disease recurrence or metastasis were detected during regular follow-up. However, the lack of a standardized classification system for GCC and the discrepancies in specific reliable markers renders their prognostic and predictive value in GCC at diagnosis insufficient. The present study also aimed to address current concerns regarding the diagnosis, treatment and prognosis of GCC, as well as the need to review and update current guidelines. To conclude, proper clinical management and the prediction of outcome for patients with GCC varies according to the classifications or staging criteria used by the clinicians; hence, a review of the current guidelines should be considered.

Low High-Density Lipoprotein Cholesterol Predisposes to Coronary Artery Ectasia.

Coronary Artery Ectasia (CAE) is a phenomenon characterized by locally or diffuse coronary artery dilation of one or more coronary arteries. In the present study, the prevalence of acquired coronary ectasia and coronary risk factors for CAE was analyzed in patients undergoing cardiac catheterization for suspected ischemic heart disease. We retrospectively analyzed 4000 patients undergoing coronary angiography for suspected coronary artery disease at our cardiac catheterization unit, and a total of 171 patients were selected. The study group was divided into three groups, 65 patients with CAE, 62 patients with significant obstructive coronary artery disease, and 44 patients with normal coronary angiograms as a control group. A negative correlation was observed between high-density lipoprotein cholesterol (HDL-C) and the presence of CAE (r = -0.274, p < 0.001). In addition, HDL-C (OR, 0.858; CI, 0.749-0.984; p = 0.029), low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (OR, 1.987; CI, 1.542-2.882; p = 0.034), and hemoglobin (OR, 2.060; CI, 1.114-3.809; p = 0.021) were identified as independent risk factors for the development of CAE. In fact, we observed that a one-unit increase in HDL-C corresponded to a 15% risk reduction in CAE development and that each unit increase in hemoglobin could potentially increase the CAE risk by 2-fold. Low HDL-C could significantly increase the risk of developing CAE in healthy individuals. Elevated hemoglobin could predispose to subsequent dilation and aneurysm of the coronary artery. This work suggests that disordered lipoprotein metabolism or altered hemoglobin values can predispose patients to aneurysmal coronary artery disease.

Increased serum levels of Galectin-9 in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults. Despite improvements in treatment, CLL is still considered an incurable disease. The aim of the present study was to evaluate galectin-1, -3 and -9 (Gal-1, -3 and -9) and Gal-3 binding protein (Gal-3BP) as prognostic and predictive factors in patients with CLL. Serum concentrations of Gal-1, -3 and -9 and Gal-3BP were measured in 48 patients with CLL and 30 control patients, using multiplex bead arrays. In patients with CLL, galectin concentrations were assessed prior to, during and following treatment. In patients with CLL who were untreated, galectin concentrations were measured twice with a 6-month interval. The serum level of Gal-9 was significantly increased (P<0.0001) in patients with CLL compared with the control group, and was associated with the clinical stage according to Binet classification, as well as poor cytogenetic and serum CLL prognostic factors. In addition, patients with CLL, who exhibited treatment failure, exhibited higher concentrations of Gal-9 (P=0.06) and Gal-3BP (P=0.009) at the end of the treatment when compared with patients under complete remission or stabilization of the disease. The serum level of Gal-3 was significantly decreased (P=0.012) in patients with CLL compared with the control group. These results suggest that Gal-9 is a potential prognostic factor in patients with CLL. The predictive value of Gal-9 requires further study in larger cohorts of patients.

Exenatide modulates expression of metalloproteinases and their tissue inhibitors in TNF-α stimulated human retinal pigment epithelial cells.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common complications of diabetes and the leading cause of acquired blindness in adults. In diabetic patients hyperglycemia induces complex metabolic abnormalities affecting retinal homeostasis, and promotes retinal inflammation and angiogenesis. Incretin mimetic drugs such exenatide, are a relatively new group of drugs used in the treatment of diabetes. We investigated the potential direct effects of exenatide on human retinal pigment epithelium (HRPE). METHODS: cAMP production was measured after stimulation of HRPE cells with GLP-1 and exenatide. Intracellular signaling pathways were also examined. HRPE cells were stimulated with TNF-α and subsequently incubated with exenatide. The concentration of metalloproteinases, MMP-1, MMP-2 and MMP-9, and tissue inhibitors of metalloproteinases, TIMP-1, TIMP-2, and TIMP-3 were evaluated. Viability, cytotoxicity and caspase 3/7 activation were determined. Activity of dipeptidyl peptidase-4 (DPP-4), an enzyme involved in GLP-1 inactivation, was also determined. RESULTS: Both GLP-1 and exenatide stimulation in HRPE cells caused no effect in cAMP levels suggesting alternative signaling pathways. Signaling pathway analysis showed that exenatide reduced phosphorylation of Akt-Ser473, PRAS40, SAPK/JNK, Bad, and S6 proteins but not Akt-Thr308. Exenatide also decreased MMP-1, MMP-9, and TIMP-2 protein levels whereas MMP-2 level in HRPE cells was increased. Finally, we show that exenatide decreased the activity of DPP-4 in TNF-α stimulated HRPE cells. CONCLUSIONS: These findings indicate that exenatide modulates regulation of extracellular matrix components involved in retinal remodeling.

Incretin drugs as modulators of atherosclerosis.

Atherosclerosis is a major underlying cause of ischemic heart diseases, ischemic stroke, and peripheral artery disease. Atherosclerotic plaque progression is characterized by chronic progressive inflammation of the arterial wall, endothelial cell dysfunction, and subendothelial lipoprotein retention. Incretin drugs, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase-IV (DPP-IV) inhibitors, are promising anti-hyperglycemic agents used for the treatment of type 2 diabetes mellitus (T2DM). In addition to glucose-lowering effects, emerging data suggest that incretin drugs have anti-atherogenic effects with the potential to stabilize atherosclerotic plaques and treat arterial inflammation. Clinical and preclinical studies have reported a plethora of therapeutic benefits of incretin drugs, including modulation of inflammatory response, reduction of intima-media thickening, improvement in lipid profiles, endothelial and smooth muscle cell modulation. Despite extensive research and widespread clinical use of incretin-based therapies, the research on the incretin hormones continues to expand. This review outlines clinical studies, molecular aspects, and potential therapeutic implications of incretin drugs in attenuation of atherosclerosis.

Pacemaker lead endocarditis: A rare cause of relapsing brucellosis.

Implantable cardioverter-defibrillator endocarditis is a rare and potentially life threatening complication of brucellosis of difficult management for clinicians. We report an unusual case of pacemaker-related endocarditis due to Brucella melitensis in a patient with previous history of neurobrucellosis. Our patient was admitted to a hospital with severe swelling of his pacemaker pocket implanted 8 years earlier for sick sinus syndrome. Although pocket site cultures were positive for Brucella but blood cultures were not and serologic titer by the Rose Bengal test was positive. Transesophageal echocardiography showed two vegetations on the pacemaker leads. The patient was treated with doxycycline, rifampin and gentamicin with full recovery and the entire pacemaker apparatus was surgically explanted. Interestingly, two year prior this admission, the patient presented with meningoencephalitis diagnosed with neurobrucellosis proven by positive growth of Brucella mellitensis from the CSF. The patient was treated with doxycycline, rifampin and gentamicin with full recovery and the pacemaker had been removed. Reports of Brucella infection of prosthetic implants and devices have increased over the past decade. Consequently, potential relapsing of the disease and occupational exposure to Brucella should be considered in the differential diagnosis and management of cardiac device infection.

Exenatide modulates metalloproteinase expression in human cardiac smooth muscle cells via the inhibition of Akt signaling pathway.

BACKGROUND: Incretin analogue drugs, a FDA-approved treatment in diabetes, has been tested for its therapeutic properties as modulators of atherosclerosis. We investigated the effects of incretin drugs on the modulation of gene expression and protein levels of matrix metalloproteinases (MMPs) as well as their inhibitors - tissue inhibitors of metalloproteinases (TIMPs) in coronary artery smooth muscle cells (hCASMC) in the context of atherosclerotic plaque formation and inflammation. METHODS: TNFα-stimulated hCASMC were treated with Glucagon-like Peptide 1 (GLP-1) (10nM and 100nM) and Exendin-4 (1nM and 10nM). Messenger RNA (mRNA) levels and protein concentrations of MMP-1, MMP-2, MMP-9 and TIMP-1, TIMP-2 were measured and the effects on extracellular matrix turnover under TNFα-mediated microenvironment were evaluated. Intracellular signaling pathways were also examined. RESULTS: Our experiments reveal that GLP-1 receptor agonists downregulate the expression of MMP-1, MMP-2, MMP-9 in hCASMC under TNFα mediated inflammatory conditions. Signaling pathway analysis show that GLP-1 receptor agonists induced inhibition of AKT-Thr308 phosphorylation, PRAS40 and S6 proteins but not AKT-Ser473. CONCLUSIONS: These findings indicate that GLP-1 receptor agonists modulate the expression of MMPs through inhibition of AKT-Thr308 phosphorylation in hCASMC. These results suggest a possible role of incretin analogue drugs in therapy of coronary atherosclerosis.

Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a role in carcinogenesis as recognition patterns for galectins. Galectins are members of the lectin family, which show high affinity for ß-galactosides. The galectin-glycan conjugate plays a fundamental role in metastasis, angiogenesis, tumor immunity, proliferation and apoptosis. Galectins' action is mediated by a structure containing at least one carbohydrate recognition domain (CRD). The potential prognostic value of galectins has been described in several neoplasms and helps clinicians predict disease outcome and determine therapeutic interventions. Currently, new therapeutic strategies involve the use of inhibitors such as competitive carbohydrates, small non-carbohydrate binding molecules and antibodies. This review outlines our current knowledge regarding the mechanism of action and potential therapy implications of galectins in cancer.

Exenatide exhibits anti-inflammatory properties and modulates endothelial response to tumor necrosis factor α-mediated activation.

INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin-mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes. AIMS: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs). TNF-α-stimulated hCAEC and hAoEC were treated with exenatide (1 and 10 nmol/L) and GLP-1 (10 and 100 nmol/L) then evaluated for caspase 3/7 activity and assayed for protein levels of adhesion molecules sICAM-1, sVCAM-1, and P-selectin. Concentrations of matrix metalloproteinases (MMPs) MMP-1, MMP-2, MMP-9, and their inhibitors-tissue inhibitor of metalloproteinases (TIMPs), TIMP-1, TIMP-2 were also measured to evaluate the effects on extracellular matrix turnover within an inflammatory environment. Intracellular signaling pathways were evaluated via transfection of endothelial cells with a GFP vector under the NF-κB promoter. RESULTS: Our experimental data suggest that GLP-1 receptor (GLP-1R) agonists downregulate activation of NF-κB and adhesion molecules ICAM and VCAM, but not P-selectin, in both endothelial cell lines. Exendin-4 and GLP-1 modulate the expression of MMPs and TIMPs, with statistically significant effects observed at high concentrations of both incretins. Expressive modulation may be mediated by NF-κB as observed by activation of the vector when stimulated under inflammatory conditions. CONCLUSION: These findings indicate that GLP-1 analogs have anti-inflammatory properties in endothelial cells that may play an important role in preventing atherosclerosis.