Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation.

Background: MicroRNA (miRNA) have the potential to be non-invasive and attractive biomarkers for a vast number of diseases and clinical conditions; however, a reliable analysis of miRNA expression in blood samples meets a number of methodological challenges. In this report, we presented and discussed, specifically, the principles and limitations of miRNA purification and analysis in blood plasma samples collected from the left atrium during an ablation procedure on patients with atrial fibrillation (AF). Materials and Methods: Consecutive patients hospitalized in the First Department of Cardiology for pulmonary vein ablation were included in this study (11 with diagnosed paroxysmal AF, 14 with persistent AF, and 5 without AF hospitalized for left-sided WPW ablation-control group). Whole blood samples were collected from the left atrium after transseptal puncture during the ablation procedure of AF patients. Analysis of the set of miRNA molecules was performed in blood plasma samples using the MIHS-113ZF-12 kit and miScript microRNA PCR Array Human Cardiovascular Disease. Results: The miRNS concentrations were in the following ranges: paroxysmal AF: 7-23.1 ng/µL; persistent AF: 4.9-66.8 ng/µL; controls: 6.3-10.6 ng/µL. The low A260/280 ratio indicated the protein contamination and the low A260/A230 absorbance ratio suggested the contamination by hydrocarbons. Spectrophotometric measurements also indicated low concentration of nucleic acids (<10 ng/µL). Further steps of analysis revealed that the concentration of cDNA after the Real-Time PCR (using the PAXgene RNA Blood kit) reaction was higher (148.8 ng/µL vs. 68.4 ng/µL) and the obtained absorbance ratios (A260/A280 = 2.24 and A260/A230 = 2.23) indicated adequate RNA purity. Conclusions: Although developments in miRNA sequencing and isolation technology have improved, detection of plasma-based miRNA, low RNA content, and sequencing bias introduced during library preparation remain challenging in patients with AF. The measurement of the quantity and quality of the RNA obtained is crucial for the interpretation of an efficient RNA isolation.

Can transesophageal echocardiography be safely omitted in patients scheduled for elective ablation of atrial arrhythmias? Data based on the LATTEE registry.

BACKGROUND: According to the present guidelines, transesophageal echocardiography (TEE) before scheduled catheter ablation (CA) for atrial arrhythmias (atrial fibrillation [AF] or atrial flutter [AFL]) is not deemed obligatory for optimally anticoagulated patients. However, daily clinical practice significantly differs from the recommendations. AIMS: That study aimed to identify transthoracic echocardiographic parameters that could be useful in revealing patients without left atrial thrombus (LAT), thereby contributing to avoiding unnecessary TEE before scheduled CA. METHODS: This is a sub-analysis of a multicenter, prospective, observational study - LATTEE registry. A total of 1346 patients referred for TEE before scheduled CA of AF/AFL were included. RESULTS: LAT was present in 44 patients (3.3%) and absent in the remaining 1302, who were younger, more likely to have paroxysmal AF, and displayed sinus rhythm during TEE. Additionally, they exhibited a lower incidence heart failure, diabetes, systemic connective tissue disease, and chronic obstructive pulmonary disease. Furthermore, they had a lower CHA2DS2-VASc score and a higher prevalence of direct oral anticoagulants. Echocardiographic parameters, including left ventricular ejection fraction (LVEF) > 65%, left atrial diameter (LAD) < 40 mm, left atrial area (LAA) < 20 cm2, left atrial volume (LAV) < 113 ml, and left atrial volume index (LAVI) < 51 ml/m2, demonstrated 100% sensitivity and 100% negative predictive value for the LAT absence, and weremet by 417 patients. Additional echocardiographic indices: LVEF/LAD > 1.4, LVEF/LAVI > 1.6 and LVEF/LAA > 2.7 identified an additional 57 patients, bringing the total predicted LAT-free patients to 474 (35%). CONCLUSIONS: Simple echocardiographic parameters could help identify individuals for whom TEE could be safely omitted before scheduled for elective CA due to atrial arrhythmias.

Functional tricuspid regurgitation and efficacy of electrical cardioversion in patients with atrial fibrillation and atrial functional mitral regurgitation.

INTRODUCTION: Atrial functional mitral regurgitation (afMR) is common in patients with atrial fibrillation (AF). The presence of functional tricuspid regurgitation (fTR), which arises as a secondary effect of afMR, has the potential to impact the effectiveness of procedures aimed at restoring normal heart rhythm. In this study, we sought to evaluate the efficacy of electrical cardioversion (CVE) in AF regarding the presence and degree of fTR in patients with afMR. MATERIAL AND METHODS: Retrospective analysis included 521 patients with persistent AF on optimal medical therapy undergoing CVE. 157 (30.1%) patients had afMR (characterized by left ventricle ejection fraction ≥ 50% and LA dilatation) and were divided into 2 groups: the group with fTR (107, 68.2%) and the group without fTR (50, 31.9%). RESULTS: Patients with afMR and fTR had a higher prevalence of metabolic syndrome (p = 0.02) and greater right atrial area (p < 0.01) compared to patients without fTR. The efficacy of CVE was lower in the group with fTR in comparison to patients with isolated afMR (82.2% vs. 94%; p = 0.048) and it was unrelated to the degree of fTR (p = 0.15) and RVSP (p = 0.56). The energy required for successful CVE was comparable regardless of the presence (p = 0.26) or severity of fTR (p = 0.94). CONCLUSIONS: The fTR frequently coexists with afMR and it significantly diminishes the effectiveness of CVE for treating AF. The degree of fTR does not appear to influence the efficacy of CVE.

Atrial septum anatomy as a predictor of ischemic neurological episodes in patients with a patent foramen ovale.

BACKGROUND: The correlation between atrial septum anatomy and the risk of ischemic neurological events remains underexplored. AIMS: This study aimed to examine both the functional and anatomical attributes of the atrial septum and identify predictors of stroke and/or transient ischemic attack (TIA) in patients diagnosed with patent foramen ovale (PFO). METHODS: A total of 155 patients diagnosed with PFO, with a cardiological cause of neurological events, were enrolled. Transesophageal echocardiography was utilized to assess the anatomy of the PFO canal, size of the right-to-left shunt, thickness of the primary and secondary atrial septum, presence of atrial septum aneurysm, and anatomical structures of the right atrium. RESULTS: Regression analysis showed that factors such as female sex, hypercholesterolemia, PFO canal width, and a large right-to-left shunt were significantly associated with stroke and/or TIA. Receiver operating characteristic analysis indicated that the width of the PFO canal holds a relatively weak, although significant predictive, value for ischemic neurological episodes (area under the curve = 0.7; P = 0.002). A PFO canal width of 4 mm was associated with 70% sensitivity and 55% specificity for predicting stroke and/or TIA. CONCLUSIONS: The atrial septum's anatomy, especially the dimensions of the PFO canal and the magnitude of the right-to-left shunt, combined with specific demographic and clinical factors, are linked to ischemic neurological incidents in PFO patients.

Electro-anatomically-guided endomyocardial biopsy in a patient with focal myocardial infiltration and chronic lymphocytic leukemia.

A 53-year-old female was admitted to the cardiology department on account of signs and symptoms of congestive heart failure (HF) with severe peripheral edema and dyspnea on exertion (New York Heart Association class III) for the past 3 months.

The Association of ADAMTS7 Gene Polymorphisms with the Risk of Coronary Artery Disease Occurrence and Cardiovascular Survival in the Polish Population: A Case-Control and a Prospective Cohort Study.

The aim of this study was to investigate whether the polymorphisms of the ADAMTS7 gene affect the risk of occurrence and mortality due to CAD. The study group included 231 patients diagnosed with CAD and 240 control blood donors. The genotyping of specified polymorphisms, i.e., rs1994016, rs3825807, and rs7173743, was performed using the TaqMan-PCR. We found that the C allele carriers of the rs1994016 and A allele carriers of the rs3825807 polymorphisms increased the risk of CAD, respectively: OR = 1.72, p = 0.036; OR = 1.64, p = 0.04. Moreover, we studied the biological interactions of specified variants, i.e., rs3825807, rs1994016, and rs7173743, and previously approved risk factors of CAD. We demonstrated here that selected polymorphisms of ADAMTS7 increased the risk of CAD altogether with abnormalities of total cholesterol and LDL concentrations in serum. Although survival analyses did not reveal statistical significance, we observed a trend for the AA genotype of the rs3825807 ADAMTS7, which may predispose to death due to CAD in a 5-year follow-up. In conclusion, the ADAMTS7 polymorphisms investigated in this study may increase the risk of occurrence and/or death due to CAD in the Polish population.

A review and recommendations for oral chaperone therapy in adult patients with Fabry disease.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding the enzyme α-galactosidase A. FD-affected patients represent a highly variable clinical course with first symptoms already appearing in young age. The disease causes a progressive multiple organ dysfunction affecting mostly the heart, kidneys and nervous system, eventually leading to premature death. Disease-specific management of FD includes enzyme replacement therapy with agalsidase α and ß or pharmacological oral chaperone migalastat. Migalastat is a low-molecular-mass iminosugar, that reversibly binds to active site of amenable enzyme variants, stabilizing their molecular structure and improving trafficking to the lysosome. Migalastat was approved in the EU in 2016 and is an effective therapy in the estimated 35-50% of all patients with FD with amenable GLA gene variants. This position statement is the first comprehensive review in Central and Eastern Europe of the current role of migalastat in the treatment of FD. The statement provides an overview of the pharmacology of migalastat and summarizes the current evidence from the clinical trial program regarding the safety and efficacy of the drug and its effects on organs typically involved in FD. The position paper also includes a practical guide for clinicians on the optimal selection of patients with FD who will benefit from migalastat treatment, recommendations on the optimal selection of diagnostic tests and the use of tools to identify patients with amenable GLA mutations. Areas for future migalastat clinical research have also been identified.

Artificial intelligence in detecting left atrial appendage thrombus by transthoracic echocardiography and clinical features: the Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry.

AIMS: Transoesophageal echocardiography (TOE) is often performed before catheter ablation or cardioversion to rule out the presence of left atrial appendage thrombus (LAT) in patients on chronic oral anticoagulation (OAC), despite associated discomfort. A machine learning model [LAT-artificial intelligence (AI)] was developed to predict the presence of LAT based on clinical and transthoracic echocardiography (TTE) features. METHODS AND RESULTS: Data from a 13-site prospective registry of patients who underwent TOE before cardioversion or catheter ablation were used. LAT-AI was trained to predict LAT using data from 12 sites (n = 2827) and tested externally in patients on chronic OAC from two sites (n = 1284). Areas under the receiver operating characteristic curve (AUC) of LAT-AI were compared with that of left ventricular ejection fraction (LVEF) and CHA2DS2-VASc score. A decision threshold allowing for a 99% negative predictive value was defined in the development cohort. A protocol where TOE in patients on chronic OAC is performed depending on the LAT-AI score was validated in the external cohort. In the external testing cohort, LAT was found in 5.5% of patients. LAT-AI achieved an AUC of 0.85 [95% confidence interval (CI): 0.82-0.89], outperforming LVEF (0.81, 95% CI 0.76-0.86, P < .0001) and CHA2DS2-VASc score (0.69, 95% CI: 0.63-0.7, P < .0001) in the entire external cohort. Based on the proposed protocol, 40% of patients on chronic OAC from the external cohort would safely avoid TOE. CONCLUSION: LAT-AI allows accurate prediction of LAT. A LAT-AI-based protocol could be used to guide the decision to perform TOE despite chronic OAC.

'A series of unfortunate events': a case report of infective endocarditis resulting from ventricular arrhythmia ablation.

Background: Radiofrequency ablation (RFA) is the most effective non-pharmacological approach in the reduction of ventricular tachycardia (VT) recurrence. However, it is crucial to thoroughly screen every patient for contraindications for RFA and provide appropriate pharmacological prophylaxis, if needed, since adverse effects may be fatal. Case summary: A 77-year-old male with multi-vessel coronary artery disease, heart failure with reduced ejection fraction (New York Heart Association (NYHA) Class III), with implantable cardioverter-defibrillator was admitted to our clinic due to recurrent life-threatening VT. The patient presented several concomitant diseases: dyslipidaemia, hypertension, and chronic kidney disease in Stage IIIB. He had a history of two myocardial infarctions and coronary artery bypass grafts complicated by mediastinitis and dehiscence of a sternotomy scar (2013). Radiofrequency ablation and pace mapping of VT were performed in sterile conditions, but no pre-operative antibiotic prophylaxis was administered. There were no local or general complications in the post-operative period. The patient was discharged from the clinic in good condition. A week later, the patient suffered from septic shock and infective endocarditis of mitral valve complicated with infiltration of the ventricular septum, wall dissection of the left ventricle (LV), pseudoaneurysm, and abscess of the LV. At the time of the second hospitalization extensive dental carries were found and oral cavity sanitation was performed. Due to the severity of the condition, patient did not survive. Conclusion: Oral cavity infections are common but often overlooked, mainly when the RFA procedure is urgent. A thorough physical examination, including a dental check-up, is crucial to minimize the risk of potential infection of the endocardial tissue and maximize the benefits of the therapy. Still, it is possible that the myocardial infection was not a result of oral cavity infection but a result of other undiagnosed and untreated infection. Contamination of the procedure site with patients' own microbiota or foreign microorganisms by the medical personnel is also a likely and unfortunate scenario. The presented case highlights the significance of not only prophylaxis, screening, and treatment of possible inflammation sites before RFA but also the need for sustaining sanitary standards and sterile conditions.

Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.

BACKGROUND: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. METHODS: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. RESULTS: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. CONCLUSION: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

Clinical characteristics and risk factors of in-hospital mortality among patients undergoing percutaneous pericardiocentesis.

Background: Percutaneous pericardiocentesis represents a salvage procedure in case of cardiac tamponade and diagnostic procedure in chronic pericardial effusion of unknown source. The study aimed to analyze the clinical characteristics of patients subject to pericardiocentesis and the predictors of in-hospital mortality. Methods: The study represents a registry that covered consecutive patients undergoing percutaneous pericardiocentesis from 2011 to 2022 in high-volume tertiary reference center. Electronic health records were queried to obtain demographic and clinical variables. The primary endpoint was in-hospital mortality, while secondary endpoint was the need for recurrent pericardiocentesis. Results: Out of 132 456 patients hospitalized in the prespecified period, 247 patients were subject to percutaneous pericardiocentesis (53.9% women; median age of 66 years) who underwent 273 procedures. In-hospital death was reported in 14 patients (5.67%), while recurrent pericardiocentesis in 24 patients (9.72%). Iatrogenic cause was the most common etiology (42.5%), followed by neoplastic disease (23.1%) and idiopathic effusion (14.57%). In logistic regression analysis in-hospital mortality was associated with myocardial infarction (MI)-related etiology (p = 0.001) and recurrent/persistent cardiogenic shock (p = 0.001). Conclusions: Iatrogenic etiology and neoplastic disease seem to be the most common indications for pericardiocentesis, while in-hospital mortality was particularly high in patients with spontaneous tamponade in the course of MI.

Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function.

Aortic valve stenosis (AS) is a common heart valve disease in the elderly population, and its pathogenesis remains an interesting area of research. The degeneration of the aortic valve leaflets gradually progresses to valve sclerosis. The advanced phase is marked by the presence of extracellular fibrosis and calcification. Turbulent, accelerated blood flow generated by the stenotic valve causes excessive damage to the aortic wall. Elevated shear stress due to AS leads to the degradation of high-molecular weight multimers of von Willebrand factor, which may involve bleeding in the mucosal tissues. Conversely, elevated shear stress has been associated with the release of thrombin and the activation of platelets, even in individuals with acquired von Willebrand syndrome. Moreover, turbulent blood flow in the aorta may activate the endothelium and promote platelet adhesion and activation on the aortic valve surface. Platelets release a wide range of mediators, including lysophosphatidic acid, which have pro-osteogenic effects in AS. All of these interactions result in blood coagulation, fibrinolysis, and the hemostatic process. This review summarizes the current knowledge on high shear stress-induced hemostatic disorders, the influence of AS on platelets and antiplatelet therapy.

Takotsubo syndrome with several hypertensive crises: an unexpected diagnosis.

We present an unusual clinical case of a 39-year-old woman admitted to the Department of Cardiology due to stenocardial pain accompanied by hypertensive crisis. The patient presented with severe chest pain and high blood pressure, along with a history of type 2 diabetes, hyperlipidemia, smoking, and hypertension. Initial tests showed elevated troponin T, glucose, CRP, and D-dimer levels, and electrocardiography and transthoracic echocardiography showed abnormalities suggesting acute myocardial infarction, but angiography did not reveal any significant coronary artery blockages. Further tests and imaging led to a diagnosis of takotsubo syndrome (TTS) and suspicion of pheochromocytoma, which was confirmed later biopsy. The presented case is very rare because the coexistence of TTS and pheochromocytoma is not common due to the rarity of the tumor. It is very important to make a quick and accurate diagnosis, because improperly treated cases can lead to death.