Gut barrier dysfunction, endotoxemia and inflammatory response in STEMI patients and effect of primary PCI.

BACKGROUND: Gut-derived bacterial and endotoxin translocation induce systemic inflammation, which exerts a pivotal pathogenetic role in all phases of atherosclerosis. OBJECTIVES: To investigate prospectively the gut barrier function, endotoxin translocation and inflammatory response in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary artery intervention (PPCI). METHODS: Twenty-seven patients with STEMI that underwent successful PPCI were subjected to peripheral blood sampling at 3-time points; before PPCI (day0), 24 hours (day1) and 96 hours (day4) after PPCI and were compared with 20 chronic coronary syndrome (CCS) patients and 11 healthy controls. Serum ZO-1, I-FABP and endotoxin concentrations were determined by ELISA. Concentrations of cytokines IL-1ß, -6, -8, -10 and TNF-α were determined by flow cytometry. RESULTS: Patients with STEMI before PPCI (day0) had increased serum ZO-1 and endotoxin, both at significantly higher levels compared to CCS patients. STEMI induced also significant increases of the cytokines IL-6, -8 and -10. After PPCI, a significant improvement of gut barrier integrity (ZO-1) and endotoxemia was observed from the first day. At day4 post PPCI, systemic endotoxin and cytokines IL-6, -8 and -10 levels were reduced to control levels. Serum ZO-1 levels were positively correlated with systemic IL-10 concentrations (r=0.471). In STEMI patients, serum endotoxin concentrations before PPCI (day0) were negatively correlated with the ejection fraction (EF) at hospital discharge. CONCLUSION: STEMI is associated with gut barrier dysfunction, systemic endotoxemia and inflammatory response, which improve rapidly following successful PPCI.

Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

BACKGROUND: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. METHODS: Thirty-three patients with stage I-IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1ß, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. RESULTS: Patients with stage I-IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. CONCLUSION: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response.

Mechanisms of Atrial Fibrillation: How Our Knowledge Affects Clinical Practice.

Atrial fibrillation (AF) is a very common arrhythmia that mainly affects older individuals. The mechanism of atrial fibrillation is complex and is related to the pathogenesis of trigger activation and the perpetuation of arrhythmia. The pulmonary veins in the left atrium arei confirm that onfirm the most common triggers due to their distinct anatomical and electrophysiological properties. As a result, their electrical isolation by ablation is the cornerstone of invasive AF treatment. Multiple factors and comorbidities affect the atrial tissue and lead to myocardial stretch. Several neurohormonal and structural changes occur, leading to inflammation and oxidative stress and, consequently, a fibrotic substrate created by myofibroblasts, which encourages AF perpetuation. Several mechanisms are implemented into daily clinical practice in both interventions in and the medical treatment of atrial fibrillation.

Dual Antiplatelet Therapy and Cancer; Balancing between Ischemic and Bleeding Risk: A Narrative Review.

Cardiovascular (CV) events in patients with cancer can be caused by concomitant CV risk factors, cancer itself, and anticancer therapy. Since malignancy can dysregulate the hemostatic system, predisposing cancer patients to both thrombosis and hemorrhage, the administration of dual antiplatelet therapy (DAPT) to patients with cancer who suffer from acute coronary syndrome (ACS) or undergo percutaneous coronary intervention (PCI) is a clinical challenge to cardiologists. Apart from PCI and ACS, other structural interventions, such as TAVR, PFO-ASD closure, and LAA occlusion, and non-cardiac diseases, such as PAD and CVAs, may require DAPT. The aim of the present review is to review the current literature on the optimal antiplatelet therapy and duration of DAPT for oncologic patients, in order to reduce both the ischemic and bleeding risk in this high-risk population.

Paradoxical pacing spikes during a wide complex tachycardia in biventricular defibrillator. What is the mechanism? Is it undersensing due to troubleshooting?

We present the case of a 68-year-old man with a cardiac resynchronization therapy-defibrillator Medtronic device implanted 3 years ago, admitted to our hospital due to a wide complex tachycardia with unexpected pacing spikes inside QRS complexes. Although that could be easily attributed to ventricular undersensing, more complicated mechanisms are involved, including the origin of the tachycardia, the parameters of the device, and the position of the device and the leads.

Potential Relationship Between Lifestyle Changes and Incidence of Hospital Admissions for Acute Coronary Syndrome During the COVID-19 Lockdown.

Aims: To evaluate the impact of lockdown during the COVID-19 pandemic on lifestyle changes of the general population, and on admissions for acute coronary syndrome (ACS). Methods and Results: All ACS admissions during the COVID-19 lockdown (10 March to 4 May, 2020), in 3 municipalities (3 spoke, and 1 hub hospital), in Southwestern Greece (411,576 inhabitants), were prospectively recorded and compared to the equivalent periods during 2018, and 2019. A telephone survey of 1014 participants was conducted to explore the lifestyle habits of citizens aged ≥35-years-old before and during lockdown. The median ACS incidence rate decreased from 19.0 cases per week in 2018 and 21.5 in 2019 down to 13.0 in 2020 (RR: 0.66 during the Covid-19 lockdown; 95%CI: 0.53-0.82; P = 0.0002). This was driven by a significant reduction of admissions for Non-ST elevation myocardial infarction (NSTEMI) (RR: 0.68; 95%CI: 0.52-0.88; P = 0.0037), mainly in patients with a lower burden of cardiovascular risk factors, as we noticed an inverse association between the reduction of the incidence of ACS during the Covid-19 lockdown period and the number of registered patient risk factors. There was no difference in the rates of STEMI and population-based all-cause mortality across the examined time periods. The telephone survey demonstrated reduction of passive smoking, working hours, alcohol, junk food and salt consumption, and an increase in sleeping hours, mainly in participants with a lower burden of cardiovascular risk factors. Conclusions: A significant decline in ACS admissions during the COVID-19 lockdown was noted, affecting mainly NSTEMI patients with a lower burden of cardiovascular risk factors. This was accompanied by significant lifestyle changes. Thus, it is tempting to speculate that to some extend the latter might be associated with the observed decline in ACS admissions.

Treatment of Heart Failure with Mid-Range Ejection Fraction: What Is the Evidence.

In this review, we briefly outline our current knowledge on the epidemiology, outcomes, and pathophysiology of heart failure (HF) with mid-range ejection fraction (HFmrEF), and discuss in more depth the evidence on current treatment options for this group of patients. In most studies, the clinical background of patients with HFmrEF is intermediate between that of patients with HF and reduced ejection fraction (HFrEF) and patients with HF and preserved ejection fraction (HFpEF) in terms of demographics and comorbid conditions. However, the current evidence, stemming from observational studies and post hoc analyses of randomized controlled trials, suggests that patients with HFmrEF benefit from medications that target the neurohormonal axes, a pathophysiological behavior that resembles that of HFrEF. Use of ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan is reasonable in patients with HFmrEF, whereas evidence is currently scarce for other therapies. In clinical practice, patients with HFmrEF are treated more like HFrEF patients, potentially because of history of systolic dysfunction that has partially recovered. Assessment of left ventricular systolic function with contemporary noninvasive modalities, e.g., echocardiographic strain imaging, is promising for the selection of patients with HFmrEF who will benefit from neurohormonal antagonists and other HFrEF-targeted therapies.

Bidirectional communication between neural and cardiac cells in human amniotic fluid.

OBJECTIVE: To evaluate whether amniotic fluid cells contain cardiomyocyte- and neuron-like cells. STUDY DESIGN: In this experimental study, cells from human amniotic fluid samples were analyzed for mRNA expression of microtubule-associated protein 2 (MAP-2), vimentin and oxytocin (OT) receptor via RT-PCR. Immunocytochemistry was also performed with MAP-2, OT receptor, vimentin and troponin I antibodies. RESULTS: In all samples, MAP-2, vimentin and mRNA expression were detectable. OT receptor was also detectable. The cells showed strong immunoreactivity for molecular markers of neurogenic cells including MAP-2 and vimentin. The cells also showed strong immunoreactivity for molecular markers of cardiac muscle such as troponin I and for OT receptors. This report also shows that atosiban (an OT antagonist) added to culture medium of amniotic fluid cells did not induce neurogenic and cardiomyogenic differentiation. CONCLUSIONS: The observed concurrent development of cardiomyocyte- and neuron-like cells suggests that amniotic fluid contains progenitor cells and there is bidirectional communication between both cell types.