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.

Cardiorenal multimorbidity in hospitalized cardiology patients: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

PURPOSE: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece. METHODS: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample. RESULTS: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%). CONCLUSION: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.

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.

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update.

Diabetes mellitus (DM) and heart failure (HF) are two chronic disorders that affect millions worldwide. Hyperglycemia can induce excessive generation of highly reactive free radicals that promote oxidative stress and further exacerbate diabetes progression and its complications. Vascular dysfunction and damage to cellular proteins, membrane lipids and nucleic acids can stem from overproduction and/or insufficient removal of free radicals. The aim of this article is to review the literature regarding the use of antidiabetic drugs and their role in glycemic control in patients with heart failure and oxidative stress. Metformin exerts a minor benefit to these patients. Thiazolidinediones are not recommended in diabetic patients, as they increase the risk of HF. There is a lack of robust evidence on the use of meglinitides and acarbose. Insulin and dipeptidyl peptidase-4 (DPP-4) inhibitors may have a neutral cardiovascular effect on diabetic patients. The majority of current research focuses on sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. SGLT2 inhibitors induce positive cardiovascular effects in diabetic patients, leading to a reduction in cardiovascular mortality and HF hospitalization. GLP-1 receptor agonists may also be used in HF patients, but in the case of chronic kidney disease, SLGT2 inhibitors should be preferred.

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.

Inferior myocardial wall ischemia on SPECT-MPI in patients with non dominant right coronary artery and non significant coronary artery disease.

BACKGROUND: The impact of a non-dominant right coronary artery (NDRCA), on single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)has not been clarified. METHODS AND RESULTS: We compared SPECT-MPI results of consecutive patients without significant (diameter stenosis ≥50%)coronary artery disease (CAD) and a NDRCA (Group-1), with those of patients from our database without CAD and a dominant RCA (Group-2). All patients were subjected to SPECT-MPI with I.V. infusion of adenosine, and TC99-tetrofosmin. Group-1 included 69 patients (55 men, 79.7%), mean age 66.8 ± 9.8 years. Group-2 consisted of 79 patients (56 men, 70.9%), mean age 62.7 ± 11.5. There was no difference in demographics and CAD risk factors between the two groups. The SPECT-MPI revealed inferior wall ischemia, in 35 patients (50.7%), in Group-1 and 27 patients (34.1%), in Group-2 (P = 0.041). CONCLUSIONS: A relatively high rate of reversible SPECT-MPI perfusion defects may be anticipated in patients with an unobstructed NDRCA compared to patients with a dominant RCA.

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.

Randomised comparison of JUDkins vs. tiGEr catheter in coronary angiography via the right radial artery: the JUDGE study.

AIMS: The aim of this study was to compare the performance of the Tiger-II with Judkins 3.5L/4R catheters in coronary angiography (CAG) via the transradial approach (TRA). METHODS AND RESULTS: Consecutive patients undergoing non-urgent CAG via the right TRA were randomised to either the Tiger-II (Terumo) or Judkins (3.5L/4R; Medtronic) 5 Fr catheters; 320 patients in each group were randomised. Catheter or access site change was required in 57 (17.8%) vs. 68 (21.3%) patients allocated to the Tiger-II and Judkins group, respectively (p=0.3). The study's primary endpoint of contrast volume (ml) used until completion of CAG was lower for Tiger-II vs. Judkins group: 66.8 (54.0-82.0) vs. 73.4 (60.0-94.1), p<0.001. Angiography, fluoroscopy time (min) and severe spasm rate were also significantly lower for Tiger-II vs. Judkins group: 5.52 (4.17-7.32) vs. 6.85 (5.15-9.63), p<0.00, 2.01 (1.32-3.13) vs. 2.24 (1.50-3.50), p=0.01 and 6 (2.8%) vs. 39 (12.2%), p<0.001, respectively. The Tiger-II catheter obtained better opacification grade for the right coronary artery (RCA): 4.0 (4.0-4.0) vs. 4.0 (3.0-4.0), p=0.02, but slightly compromised opacification of the left anterior descending (LAD) and left circumflex (LCX) arteries compared with the Judkins group: 3.75 (3.0-4.0) vs. 4.0 (3.5-4.0), p<0.001, and 3.78 (3.6-4.0) vs. 4.0 (3.6-4.0), p<0.001, respectively. CONCLUSIONS: The Tiger-II was found superior to the Judkins 3.5L/4R regarding contrast volume use, procedural and fluoroscopy time, spasm rate and RCA imaging, and inferior regarding LAD and LCX imaging.