Empagliflozin to prevent post-operative atrial fibrillation in patients undergoing coronary artery bypass graft surgery: Rationale and design of the EMPOAF trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is one of the most common types of acute AF and can complicate the treatment course of approximately one third of patients undergoing cardiac surgery. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are among the newest antidiabetic drugs which can be therapeutic options for preventing POAF by different mechanisms. METHODS: Empagliflozin to Prevent POAF (EMPOAF) is an interventional, investigator-initiated, double-blind, placebo-controlled, multicenter, randomized controlled trial which will be conducted in two referral teaching cardiology hospitals in Tehran. Four-hundred ninety-two adult patients who are scheduled for elective isolated coronary artery bypass graft (CABG) surgery will be randomly assigned to one of the groups of intervention (empagliflozin 10 mg daily) or placebo starting at least 3 days before surgery until discharge. Key exclusion criteria are a history of diabetes mellitus, AF, ketoacidosis, or recurrent urinary tract infections along with severe renal or hepatic impairment, unstable hemodynamics, and patients receiving SGLT2 inhibitors for another indication. The primary outcome will be the incidence of POAF. Key secondary endpoints will be the composite rate of life-threatening arrhythmias, postoperative acute kidney injury, hospitalization length, in-hospital mortality, stroke, and systemic embolization. Key safety endpoints will be the rate of life-threatening and/or genitourinary tract infections, hypoglycemia, and ketoacidosis. CONCLUSIONS: EMPOAF will prospectively evaluate whether empagliflozin 10 mg daily can reduce the rate of POAF in patients undergoing elective CABG. Enrolment into this study has started by November 2023 and is expected to be ended before the end of 2025.

Bridging the gap: Navigating the impact of dietary supplements on abdominal aortic aneurysm progression- A systematic review.

BACKGROUND: Vitamins D, E, A, B, C, and Omega-3 play crucial roles in modulating inflammatory and oxidative stress pathways, both implicated in abdominal aortic aneurysm (AAA) development. Recent research has explored the potential impact of dietary supplements on AAA progression. The systematic review aims to assess interventional studies investigating the effects of various dietary supplements on the development and severity of abdominal aortic aneurysms. METHOD: A systematic search using relevant keywords related to abdominal aortic aneurysm and dietary supplements was conducted across four databases (PubMed, Embase, Scopus, and Web of Science). Quality assessment for animal studies employed SYRCLE and the Cochrane Collaboration Risk of Bias Tool for randomized control trials. The study protocol is registered in PROSPERO under the registry code CRD42023455958. RESULTS: Supplementation with Omega-3, Vitamins A, C, D, E, and the Vitamin B family exhibited positive effects in AAA progression. These supplements contributed to a reduction in AAA diameter, elastin degradation, inflammatory responses, and reactive oxygen species. Additional supplements such as Zinc, methionine, and phytoestrogen also played roles in mitigating AAA progression. CONCLUSION: The findings of this study underscore the potential role of dietary supplements in the progression of AAA. Predominantly based on animal studies, the results indicate that these supplements can limit AAA progression, primarily evidenced by their ability to mitigate inflammatory processes and oxidative stress pathways.

Detection of a novel pathogenic variant in KCNH2 associated with long QT syndrome 2 using whole exome sequencing.

BACKGROUND: Long QT syndrome (LQTS) is a cardiac channelopathy characterized by impaired myocardial repolarization that predisposes to life-threatening arrhythmias. This study aimed to elucidate the genetic basis of LQTS in an affected Iranian family using whole exome sequencing (WES). METHODS: A 37-year-old woman with a personal and family history of sudden cardiac arrest and LQTS was referred for genetic study after losing her teenage daughter due to sudden cardiac death (SCD). WES was performed and variants were filtered and prioritized based on quality, allele frequency, pathogenicity predictions, and conservation scores. Sanger sequencing confirmed segregation in the family. RESULTS: WES identified a novel heterozygous frameshift variant (NM_000238.4:c.3257_3258insG; pGly1087Trpfs*32) in the KCNH2 encoding the α-subunit of the rapid delayed rectifier potassium channel responsible for cardiac repolarization. This variant, predicted to cause a truncated protein, is located in the C-terminal region of the channel and was classified as likely pathogenic based on ACMG guidelines. The variant was absent in population databases and unaffected family members. CONCLUSION: This study reports a novel KCNH2 frameshift variant in an Iranian family with LQTS, expanding the spectrum of disease-causing variants in this gene. Our findings highlight the importance of the C-terminal region in KCNH2 for proper channel function and the utility of WES in identifying rare variants in genetically heterogeneous disorders like LQTS. Functional characterization of this variant is warranted to fully elucidate its pathogenic mechanisms and inform personalized management strategies.

Natural Killer Cell Subsets in Tumor Draining Lymph Nodes of Patients with Bladder Cancer and Their Clinical Implications.

Background: Natural killer (NK) cells are crucial innate components in anti-tumor immunity. However, the clinical impacts and their phenotypes in bladder cancer (BC) remain unclear. Objective: To assess the clinical significance of NK cell subsets in tumor-draining lymph nodes of patients with BC. Methods: In a cross-sectional study, pelvic lymph nodes were obtained from 49 untreated patients with BC. Mononuclear cells were isolated and immunophenotyped using CD3, CD56, CD16, CD27, and CD11b markers. NK cells were then classified based on their expression patterns of CD56/CD16 (conventional) and CD27/CD11b (new). Results: On average, NK cells constituted 2.99±1.44% of the total lymphocytes in the draining lymph node of patients with BC. The CD56dim and regulatory NK subsets (CD27+CD11b+/-) were the predominant old and new NK, respectively. The NK cells significantly increased in patients with at least one involved node (LN+) compared with those with free nodes (LN-; p=0.022). Conversely, CD56dimCD16- subset significantly decreased in higher stages (p=0.032) and in tumors with muscle invasion (p=0.038). Significant variations were also observed in different T-stages (p<0.05). Regarding new classification, the frequency of CD11b+ regulatory NK cells was significantly lower in node-positive patients (p=0.025). Conclusion: These findings emphasize the dynamic nature of NK cell subsets in bladder cancer and their potential relevance in disease progression and management, suggesting potential implications for therapeutic strategies targeting these specific subsets.

Assessing the impact of omega-3 fatty acids on ventricular tachyarrhythmia and survival in patients with ICDs: A systematic review and meta-analysis.

Background: Recent studies investigating the effects of fish oil on shocks administered by ICDs in patients with ventricular tachycardias produced inconclusive results. This systematic review aims to evaluate the effectiveness of omega-3 polyunsaturated fatty acids in lowering the risk of life-threatening VTs among individuals with implantable cardioverter-defibrillators. Methods: We searched five databases, including Central, PubMed, EMBASE, Web of Science, and Scopus, for studies evaluating the efficacy of omega-3 polyunsaturated fatty acids (PUFAs) for the prevention of ICD events for VT or VF, published up to December 1, 2023. Results: Four trials were finally included in the study. The pooled risk ratios for mortality and ICD events were 0.87 (95% CI:0.58-1.32) and 0.75 (95% CI:0.48-1.18), respectively. Conclusion: No significant effect was discovered to support the antiarrhythmic properties or survival advantages of n-3 polyunsaturated fatty acids (PUFA) in individuals with implanted implantable cardioverter-defibrillators (ICD).

Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.

The giant protein titin (TTN) is a sarcomeric protein that forms the myofibrillar backbone for the components of the contractile machinery which plays a crucial role in muscle disorders and cardiomyopathies. Diagnosing TTN pathogenic variants has important implications for patient management and genetic counseling. Genetic testing for TTN variants can help identify individuals at risk for developing cardiomyopathies, allowing for early intervention and personalized treatment strategies. Furthermore, identifying TTN variants can inform prognosis and guide therapeutic decisions. Deciphering the intricate genotype-phenotype correlations between TTN variants and their pathologic traits in cardiomyopathies is imperative for gene-based diagnosis, risk assessment, and personalized clinical management. With the increasing use of next-generation sequencing (NGS), a high number of variants in the TTN gene have been detected in patients with cardiomyopathies. However, not all TTN variants detected in cardiomyopathy cohorts can be assumed to be disease-causing. The interpretation of TTN variants remains challenging due to high background population variation. This narrative review aimed to comprehensively summarize current evidence on TTN variants identified in published cardiomyopathy studies and determine which specific variants are likely pathogenic contributors to cardiomyopathy development.

Comparative analysis of infective endocarditis in hemodialysis versus non-hemodialysis patients in Iran: implications for clinical practice and future research.

BACKGROUND: In hemodialysis (HD) patients, there is a larger frequency of mortality and morbidity associated with infective endocarditis (IE) as opposed to the general population. Despite the increased burden of IE in the HD population, optimal strategies for prevention and management still need to be clarified. Elucidating the distinguishing features and outcomes of IE in HD patients is crucial to guide clinical decision-making and improve prognosis in this high-risk group. However, the details of IE characteristics, specifically in HD patients in the Middle East, are limited. OBJECTIVE: To compare the clinical characteristics and short-term outcomes of IE between HD and non-HD patients. METHODS: A retrospective analysis was carried out on 139 patients with infective endocarditis who were referred to a tertiary cardiovascular center in Iran from 2006 to 2018. The participants were split into HD (n = 34) and non-HD (n = 105) groups. Data pertaining to demographic characteristics, comorbidities, microbiological findings, occurrence of complications, therapeutic interventions, and mortality rates during hospital stay were gathered. RESULTS: Diabetes, hypertension, and congestive heart failure were observed more frequently in HD patients. HD patients were more likely than non-HD patients to have involvement of the right valve (41.2% vs. 20.9%), larger vegetation, and extracardiac emboli. In-hospital mortality was 41.2% for HD patients versus 14.3% for non-HD patients. Mortality remained high after valve surgery in HD patients (38.2% vs. 10.5% in non-HD). CONCLUSION: HD patients exhibited a distinct clinical profile of IE with worse short-term outcomes, including higher mortality.

Catecholaminergic polymorphic ventricular tachycardia (and seizure) caused by a novel homozygous likely pathogenic variant in CASQ2 gene.

BACKGROUND: Although structural heart disease is frequently present among patients who experience sudden cardiac death (SCD), inherited arrhythmia syndromes can also play an important role in the occurrence of SCD. CPVT2, which is the second-most prevalent form of CPVT, arises from an abnormality in the CASQ2 gene. OBJECTIVE: We represent a novel CASQ2 variant that causes CPVT2 and conduct a comprehensive review on this topic. METHODS: The proband underwent Whole-exome sequencing (WES) in order to ascertain the etiology of CPVT. Subsequently, the process of segregating the available family members was carried out through the utilization of PCR and Sanger Sequencing. We searched the google scholar and PubMed/Medline for studies reporting CASQ2 variants, published up to May 10,2023. We used the following mesh term "Calsequestrin" and using free-text method with terms including "CASQ2","CASQ2 variants", and "CASQ2 mutation". RESULTS: The CASQ2 gene was found to contain an autosomal recessive nonsense variant c.268_269insTA:p.Gly90ValfsTer4, which was identified by WES. This variant was determined to be the most probable cause of CPVT in the pedigree under investigation. CONCLUSION: CASQ2 variants play an important role in pathogenesis of CPVT2. Notabely, based on results of our study and other findings in the literature the variant in this gene may cause an neurological signs in the patients with CPVT2. Further studies are needed for more details about the role of this gene in CPVT evaluation, diagnosis, and gene therapy.

Clinical outcomes of optical coherence tomography versus conventional angiography guided percutaneous coronary intervention: A meta-analysis.

BACKGROUND: Performing optical coherence tomography (OCT) as a guide for percutaneous coronary intervention (PCI) compared to conventional coronary angiography has been the subject of the recent cohorts and randomized trials. However, clear evidence demonstrating its superiority is still controversial. METHODS: We performed a thorough search in digital databases to find the relevant observational studies and randomized trials comparing OCT and angiography in patients undergoing PCI. A random-effects meta-analysis was undertaken comparing clinical outcomes to generate an odds ratio (OR) with a corresponding 95% confidence interval (CI). Subgroup analyzes were performed based on study design, underlying cardiac condition, and complexity of cases. RESULTS: A total of 21 studies (10 RCTs and 11 observational studies) with 11,163 participants (5319: OCT and 5844: angiography group) were included for quantitative synthesis. Performing OCT was associated with lower odds of all-cause (OR (95% CI) = 0.56 (0.48; 0.67)) and cardiac mortality (OR (95% CI) = 0.47 (0.35; 0.63)), major adverse cardiovascular events (OR (95% CI) = 0.60 (0.48; 0.76)), myocardial infarction (OR (95% CI) = 0.79 (0.64; 0.97)), and stent thrombosis (OR (95% CI) = 0.61 (0.39; 0.96)) compared to the angiography group. Other clinical outcomes were similar between the studied groups. The outperformance of OCT was more evident in observational studies and the ones with PCI on complex lesions. CONCLUSION: Performing OCT prior to PCI is associated with better clinical outcomes compared to angiography alone based on contemporary evidence. Future well-designed randomized trials are needed to confirm the findings of this meta-analysis.

Has the COVID-19 pandemic affected ureteral stone management in pregnant women? A retrospective single-center study.

INTRODUCTION: This study aimed to evaluate the effect of coronavirus disease (COVID-19) on the patients' referral in the pregnant population and also investigate each treatment approach's advantages and disadvantages for acute renal colic in pregnancy. METHODS: In this retrospective study, we included all pregnant women with ureteral stones referred to a referral center between January 2019 and March 2021. RESULTS: Among 53 pregnant women, 18 (33.9%) were on conservative therapy, which passed the stone without any complications. Double J stent or nephrostomy tube insertion was done for 24 patients (45.2%). Seventeen of these patients (70.8%) presented post-surgical complications, including hematuria (29.2%), pyelonephritis (20.8%), and lower urinary tract symptoms (20.8%). Transurethral lithotripsy (TUL) was done in 11 patients (20.7%). Only one of these patients developed hematuria following TUL. Thus, in our population study, double J stent or nephrostomy insertion was associated with a higher chance of postoperative complications than TUL (p-value = 0.001). Thirty-six patients were referred within 13 months before the entry of COVID-19, while 17 were referred during a similar approximate duration after the COVID-19 entry into the country. Only the initial presentation had a significant difference between these two periods (p-value = 0.034). CONCLUSIONS: When conservative treatment fails, we recommend TUL as the second-line treatment over temporary procedures, such as double J stent or nephrostomy insertion. Of note, in a group of patients with an emergent clinical setting, including active infection, deteriorating renal function, signs of preterm labor, solitary kidney, etc., double J or nephrostomy tube insertion remains the preferred management method for its fast resolution of obstruction and infection. Besides, a decrease in visits with an increase in complicated cases after COVID-19 was observed, maybe due to a delay in referring.