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".

Genome Editing and Atrial Fibrillation.

Atrial fibrillation (AF) is a frequent rhythm disturbance that raises the possibility of heart failure (HF) and stroke. AF is a multifactorial disorder combining genetic and environmental etiologies. Over the last decade, advancements have been made regarding the genetic base of this arrhythmia. We present the existing knowledge of genetic analysis and genome editing for atrial fibrillation, indicating the existing gaps and future directions. We aim to elucidate how genome editing could be utilized for patients with atrial fibrillation.

KLF4 Upregulation in Atherosclerotic Thoracic Aortas: Exploring the Protective Effect of Colchicine-based Regimens in a Hyperlipidemic Rabbit Model.

BACKGROUND: Inflammatory dysregulation of KLF4 is related to atheromatosis. In the present study, we explored the impact of colchicine-based regimens on the development of thoracic aortic atheromatosis and KLF4 expression. METHODS: Twenty-eight New Zealand White rabbits were divided to 4 groups. The control group (n = 6) was fed standard chow, group A (n = 6) was fed chow enriched with 1% w/w cholesterol, group B (n = 8) was fed the same cholesterol-enriched diet plus 2 mg/kg body weight/day colchicine and 250 mg/kg body weight/day fenofibrate, while group C (n = 8) was also fed the same diet plus 2 mg/kg body weight/day colchicine and 15 mg/kg body weight/day N-acetylcysteine. After 7 weeks, all animals were euthanized, and their thoracic aortas were isolated. Atherosclerotic plaque area was estimated with morphometric analysis. KLF4 expression was quantified with quantitative RT-PCR. RESULTS: Group A developed significantly more atherosclerosis compared to group B (MD: 13.67, 95% CI: 7.49-19.84) and C (MD: 20.29, 95% CI: 14.12-26.47). Colchicine with N-acetylcysteine resulted in more pronounced reduction in the extent of atherosclerotic plaques compared to colchicine/fibrate (MD: 6.62, 95% CI: 0.90-12.34). Group A exhibited significantly greater KLF4 expression compared to group B (MD: 4.94, 95% CI: 1.11-8.77) and C (MD: 9.94, 95% CI: 6.11-13.77). Combining colchicine with N-acetylcysteine instead of fenofibrate (MD: 5.00, 95% CI: 1.45-8.54) led to a more robust reduction in KLF4 expression. CONCLUSIONS: In the present hyperlipidemic animal model, colchicine-based regimens curtailed de novo atherogenesis and KLF4 overexpression in thoracic aortas.

Thyroid cancer surgery during the coronavirus disease 2019 pandemic: perioperative management and oncological and anatomical considerations.

The coronavirus disease 2019 (COVID-19) pandemic has changed many aspects of our everyday lives and medical practice, including oncology treatment; thyroid cancer surgery is not an exception. The reported number of fine-needle aspirations performed during the first semester of 2020 was significantly reduced. Poorly differentiated, medullary and anaplastic thyroid tumors are considered important indications for immediate surgical intervention. By contrast, most well-differentiated carcinomas present slow growth, and thus surgery can be deferred for a short period of time during which patients are under active surveillance. Thyroid surgeries have decreased during the COVID-19 pandemic. Furthermore, prior to any intervention, negative COVID-19 status - with the use of a nasopharyngeal swab and reverse transcription PCR assay as the gold standard and chest CT scan as a complementary modality in some cases - must be confirmed to achieve a COVID-free pathway. Thorough preoperative assessment regarding both oncological and anatomical aspects should be performed to identify optimal timing for safe management.

Wenckebach cycle length: A novel predictor for AV block in AVNRT patients treated with ablation.

BACKGROUND: Radiofrequency catheter ablation remains the most effective management option for atrioventricular nodal reentry tachycardia (AVNRT). The risk of atrioventricular (AV) block requiring permanent pacemaker is substantial, but, currently, a reliable method to predict this complication is lacking. METHODS: The electrophysiologic studies (EPS) and baseline characteristics of patients who underwent catheter ablation for the treatment of AVNRT were retrospectively analyzed to investigate predisposing factors for AV block after treatment. Patients were followed for AV block at one month and one year after hospital discharge. RESULTS: Among 784 patients treated with catheter ablation for AVNRT between 1999 to 2019, 15 developed AV block. Patients with AV block were older (p = .001). Among the recorded EPS parameters, patients with AV block had significantly higher Atrial His interval (120 vs. 110 ms, p = .049), Wenckebach cycle length (WCL) (400 vs. 353 ms, p < .001) and tachycardia CL (400 vs. 387 ms, P = .01) during the ablation compared to their peers without AV block. Additionally, only WCL (OR = 1.1, 95% CI 1.02-1.19, p = .017) remained significant after adjustment for age, gender, ERP, AH interval, and HR. This association was confirmed by comparing patients with (n = 15) and without (n = 15) AV block using propensity score-matching. A WCL≥400ms was associated with a 4-fold higher incidence of AV block (4.79% vs. 1.25%). CONCLUSION: Increased pre-procedural WCL was associated with a high risk for AV block after catheter ablation treatment for AVNRT. These findings suggest that this readily available EPS-derived parameter may be a novel marker of risk for severe complications in these patients.

Diagnosis, family screening, and treatment of inherited arrhythmogenic diseases in Europe: results of the European Heart Rhythm Association Survey.

The spectrum of inherited arrhythmogenic diseases (IADs) includes disorders without overt structural abnormalities (i.e. primary inherited arrhythmia syndromes) and structural heart diseases (i.e. arrhythmogenic ventricular cardiomyopathy, hypertrophic cardiomyopathy). The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate current clinical practice and adherence to 2015 European Society of Cardiology Guidelines regarding the management of patients with IADs. A 24-item centre-based online questionnaire was presented to the EHRA Research Network Centres and the European Cardiac Arrhythmia Genetics Focus Group members. There were 46 responses from 20 different countries. The survey revealed that 37% of centres did not have any dedicated unit focusing on patients with IADs. Provocative drug challenges were widely used to rule-out Brugada syndrome (BrS) (91% of centres), while they were used in a minority of centres during the diagnostic assessment of long-QT syndrome (11%), early repolarization syndrome (12%), or catecholaminergic polymorphic ventricular tachycardia (18%). While all centres advised family clinical screening with electrocardiograms for all first-degree family members of patients with IADs, genetic testing was advised in family members of probands with positive genetic testing by 33% of centres. Sudden cardiac death risk stratification was straightforward and in line with current guidelines for hypertrophic cardiomyopathy, while it was controversial for other diseases (i.e. BrS). Finally, indications for ventricular mapping and ablation procedures in BrS were variable and not in agreement with current guidelines in up to 54% of centres.

Electrical Storm: Current Evidence, Clinical Implications, and Future Perspectives.

PURPOSE OF REVIEW: Electrical storm (ES) is a life-threatening medical emergency of repetitive episodes of sustained ventricular arrhythmias within a short period. Its occurrence is associated with poor short- and long-term survival, even in patients with implantable cardioverter defibrillators (ICD). Management of ES is challenging and mainly based on retrospective studies. This article reviews the existing literature on ES, presents the available data regarding its management, and proposes a new algorithm based on current evidence. RECENT FINDINGS: Recent research could modify the management of ES supporting the role of non-selective ß1 and ß2 blockade and the early intervention with catheter ablation as well as strengthening the role of cardiac sympathetic denervation. A multipronged approach should be considered for the management of ES including identification and correction of reversible causes, ICD reprogramming, drug therapy (beta-blockers-especially non-selective ones-and other anti-arrhythmic drugs) and non-pharmacologic therapies such as catheter ablation and techniques of neuroaxial modulation. Although current data suggest early aggressive management, further research is required to clarify the optimal order and combination of therapies for the prevention of future events.

Cytokines as biomarkers of inflammatory response after open versus endovascular repair of abdominal aortic aneurysms: a systematic review.

The repair of an abdominal aortic aneurysm (AAA) is a high-risk surgical procedure related to hormonal and metabolic stress-related response with an ensuing activation of the inflammatory cascade. In contrast to open repair (OR), endovascular aortic aneurysm repair (EVAR) seems to decrease the postoperative stress by offering less extensive incisions, dissection, and tissue manipulation. However, these beneficial effects may be offset by the release of cytokines and arachidonic acid metabolites during intra-luminal manipulation of the thrombus using catheters in endovascular repair, resulting in systemic inflammatory response (SIR), which is clinically called post-implantation syndrome. In this systematic review we compared OR with EVAR in terms of the post-interventional inflammatory response resulting from alterations in the circulating cytokine levels. We sought to summarize all the latest evidence regarding post-implantation syndrome after EVAR. We searched Medline (PubMed), ClinicalTrials.gov and the Cochrane library for clinical studies reporting on the release of cytokines as part of the inflammatory response after both open/conventional and endovascular repair of the AAA. We identified 17 studies examining the cytokine levels after OR versus EVAR. OR seemed to be associated with a greater SIR than EVAR, as evidenced by the increased cytokine levels, particularly IL-6 and IL-8, whereas IL-1ß, IL-10 and TNF-α showed conflicting results or no difference between the two groups. Polyester endografts appear to be positively correlated with the incidence of post-implantation syndrome after EVAR. Future large prospective studies are warranted to delineate the underlying mechanisms of the cytokine interaction in the post-surgical inflammatory response setting.

Histone deacetylase inhibitors as a new anticancer option: How far can we go with expectations? delivery systems.

Histone modification that occurs through the process of acetylation plays a key role in the epigenetic regulation of gene expression. The balance between histone deacetylases (HDACs) and histone acetyltransferases controls this process. Histone deacetylase inhibitors (HDACIs) can induce cancer cell cycle arrest, differentiation and cell death, reduce angiogenesis and modulate immune response. Therefore, HDAIs represent a group of enzymes that can be used for the development of pharmaceutical agents against a variety of malignant diseases. The mechanisms of their anticancer effect depend on many factors. HDACIs vorinostat, romidepsin and belinostat have been approved for some T-cell lymphomas and panobinostat for multiple myeloma. Other HDACIs are tested in clinical trials for the treatment of hematological and solid malignancies. The results of such studies are promising but further larger studies are needed.

Anticoagulation in Patients with Atrial High-rate Episodes Detected by Cardiac Implantable Electronic Devices.

Atrial high-rate episodes (AHRE) are atrial tachyarrhythmias that are identified by the use of continuous rhythm monitoring devices such as pacemakers, defibrillators, or implantable cardiac monitors. Nevertheless, the therapeutic implications of these rhythm disturbances remain uncertain. The presence of AHRE is associated with an increased risk of stroke as compared to patients who do not exhibit AHRE. The utilisation of oral anticoagulation has the ability to mitigate the likelihood of stroke occurrence in patients with AHRE. However, it is important to note that this treatment approach is also linked to a severe bleeding rate of approximately 2% per year. The stroke rate among individuals diagnosed with AHRE appears to be comparatively lower when compared to patients diagnosed with atrial fibrillation. The efficacy and safety of anticoagulation in patients with AHRE have yet to be definitively established. Further research is required to provide a comprehensive understanding of the effectiveness and safety of oral anticoagulation in individuals with AHRE.

Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine.

OBJECTIVE: Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied. MATERIAL AND METHODS: Histology in 53 IgAN patients (M/F 35/18 age 40.5 years (17 - 65)) was evaluated using the Oxford classification system. IL-1ß, -2, -4, -5, -6, -10, -12 and -17, INF-γ and MCP-1 were measured subsequently by multiplex cytokine assay in first morning urine samples taken at the day of renal biopsy. After a 6-month course with RAASinhibitors + fish oils (FO), 35/53 patients, Group A, responded and continued on the same treatment, while in 18/53 who did not respond, Group B, steroids + azathiopine were added. RESULTS: The presence of endocapillary proliferation had significant correlation with the urinary excretion of pro-inflammatory and pro-fibrotic cytokines (IL-1ß, MCP-1, IL-17, INF-γ, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1ß (p = 0.03), IL-2 (p = 0.01) and MCP-1 (p = 0.03). GFR was reduced from 65 ± 29 to 57 ± 34 ml/min, p = 0.005 in Group A and remained stable in Group B patients (GFR from 63 ± 24 to 61 ± 30 ml/min, p = NS). Most of the measured cytokines in the urine predicted deterioration of renal function in Group A, but the urinary excretion of IL-6 seemed to predict renal function outcome in both groups of patients. CONCLUSION: Several cytokines are excreted in the urine of patients with IgAN, and their levels predict the outcome of the disease. Steroids + aza may exert their beneficial effect through suppression of the production or activation of most cytokines.