Reply to Ross, K. Comment on "Polak et al. Principles and Limitations of miRNA Purification and Analysis in Whole Blood Collected during Ablation Procedure from Patients with Atrial Fibrillation. J. Clin. Med. 2024, 13, 1898".

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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.

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.

Positive left atrial remodeling in patients with paroxysmal atrial fibrillation after a successful radiofrequency pulmonary vein isolation.

BACKGROUND: A potential relationship between the initial left atrial (LA) echocardiographic parameters and LA remodeling after pulmonary vein isolation using (PVI) radiofrequency energy energy with effectiveness of this treatment was discussed. AIM: We aimed to determine the relationship between initial and post-follow-up transthoracic echocardiography- derived predictors of successful PVI in patients with paroxysmal atrial fibrillation (AF). METHODS: Eighty patients with paroxysmal AF (aged 58 [interquartile range, IQR, 50-63] years; male, 50 [62.5%]), hospitalized for the first PVI procedure were included. Before and after a minimum of 6 months of follow-up, clinical and echocardiographic evaluations were performed. LA morphological parameters (diameter, volumes, and other detailed LA parameters), as well as LA peak segmental and global longitudinal strains (PLS) and LA wall strain synchrony were assessed. RESULTS: In the whole group after the follow-up period, patients presented higher mean LA Volconduit. Patients with no AF recurrences had lower post-PVI LA volumes, higher LA ejection fraction, and LA expansion index when compared to the patients after ineffective PVI. Patients who maintained sinus rhythm after the PVI procedure were characterized by higher initial segmental strains: LA PLSbasal-inferior and PLSapical-septal, as well as higher LA wall strain dispersion over time. CONCLUSIONS: Some echocardiographic parameters related to LA morphology improve after successful PVI treatment. LA strains and wall strain dispersion over time are not related to LA remodeling after a successful PVI procedure. However, the baseline LA standard and novel echocardiographic parameters cannot be used for remote evaluation of the effectiveness of the PVI procedure.

Left atrial function in obese and non-obese patients undergoing percutaneous pulmonary vein isolation.

Obesity constitutes a risk factor for atrial fibrillation (AF) and modifies the efficacy of invasive AF treatment. Left atrial (LA) global longitudinal strain (GLS), which is measured using speckle-tracking echocardiography (STE), is one of the new methods that are helpful in evaluating the function of LA. The aim of the study was to evaluate LA function in obese and non-obese patients that were undergoing percutaneous pulmonary vein isolation (PVI) before and 6 months after the procedure. 89 patients (F/M: 31/58; mean age: 55.8 ± 9.8 years) with paroxysmal or persistent symptomatic AF that had been qualified for percutaneous PVI were prospectively enrolled in the study. Body mass index (BMI) constituted as a discriminating factor for the study groups: obese group: BMI ≥ 30 kg/m2 (29 patients, F/M: 13/16, mean age: 55.13 ± 10.1 years) and non-obese group BMI < 30 kg/m2 (60 patients, F/M: 18/42, mean age: 57.17 ± 9.0 years). Transthoracic echocardiography (TTE) with LA GLS and segmental longitudinal strain were analysed 1 day before and 6 months after PVI. PVI efficacy was evaluated 6 months after PVI via a seven-day Holter monitoring. Baseline analysis revealed significantly lower two-chamber (2-Ch) LA GLS in the obese patients compared to the non-obese subjects (- 10.55 ± 3.7 vs - 13.11 ± 5.1, p = 0.004). Segmental strain analysis showed no significant differences between the groups. The data that was obtained 6 months after PVI showed a significantly lower 4-Ch LA GLS in the obese patients compared to the non-obese subjects (- 11.04 ± 5.0 vs - 13.91 ± 4.2, p = 0.02), which was accompanied by a significantly lower segmental 4-Ch LA function in the obese patients (med-sept: - 11.66 ± 11.2 vs - 15.97 ± 5.3, p = 0.04; api-sept: - 9.04 ± 6.3 vs - 13.62 ± 6.5, p < 0.001; api-lat: - 7.62 ± 4.0 vs - 13.62 ± 6.5, p < 0.001; med-lat: -9.31 + - 7.9 vs - 15.04 + - 6.3, p = 0.003, global: - 11.04 + - 5.0 vs - 13.91 + - 4.2, p = 0.02). PVI efficacy was confirmed in 52 (58.4%) patients and was similar in both groups. Comparison of the baseline and 6-month strain revealed no differences in LA GLS in either group. Differences in LA GLS before and after the procedure (delta LA GLS) were not obesity dependent. Apical-septal and apical-lateral strain in the obese group, which were measured in 4-Ch view, were significantly lower after the procedure compared to the baseline (p < 0.001). Obese patients with paroxysmal AF were characterised by impaired LA GLS, which is persistent and was accompanied by segmental dysfunction after PVI at the 6-month follow-up. PVI efficacy was comparable between the obese and non-obese patients.

Lower soluble Klotho and higher fibroblast growth factor 23 serum levels are associated with episodes of atrial fibrillation.

AIMS: The proarrhythmic effect of fibroblast growth factor 23 (FGF23) was observed in patients with end stage kidney disease (ESKD). However, there is no data on the role of FGF23 and soluble Klotho (sKlotho) in the pathogenesis of atrial fibrillation (AF) beyond ESKD. The aim of the study was to assess the peripheral vein and left atrial (LA) serum levels of FGF23 and sKlotho along with calcium-phosphates parameters in patients with AF undergoing percutaneous radiofrequency pulmonary vein isolation (PVI). METHODS AND RESULTS: Sixty-nine consecutive patients (mean age: 55.8 ±â€¯9.7 years, F/M: 26/43, CHA2DS2-Vasc: 1.7 ±â€¯1.1) with paroxysmal/persistent AF undergoing PVI were included into the study. Blood samples were taken during PVI - baseline from the peripheral vein, then from the LA immediately after a septal puncture. RESULTS: There were significant differences in the concentrations of peripheral and LA serum sKlotho, intact FGF23 (iFGF23), calcium and phosphates; peripheral FGF23, calcium and phosphates levels were significantly higher, and sKlotho levels were significantly lower than the LA concentrations. Serum sKlotho levels correlated with the CHADS2-VASc score (r = 0.254, p = 0.034) and glucose level (r = 0.300, p = 0.005). Serum sKlotho gradient (LA - peripheral vein) correlated with the baseline AF burden in the Holter monitoring (r = -0.389, p = 0.003). PVI efficacy was confirmed in 52 (75%) patients. There was a significant difference in the iFGF23 gradient between patients with AF and without AF (80.3 vs. -47.6 pg/ml, p = 0.009) in the six-month follow-up. A receiver operating characteristic (ROC) analysis revealed that an iFGF23 gradient >28.7 pg/ml (AUC = 0.742, p = 0.002) was a predictor for AF recurrence. CONCLUSIONS: There is a gradient between the LA and peripheral vein in the markers of calcium-phosphate metabolism in patients undergoing PVI. Lower sKlotho and higher iFGF23 serum levels are associated with episodes of AF. Serum iFGF23 gradient is a potent predictor for the recurrence of AF.

Renalase is associated with adverse left atrial remodelling and disease burden in patients with atrial fibrillation undergoing pulmonary vein isolation.

BACKGROUND: Renalase is a catecholamine-metabolising enzyme, but its possible association with atrial fibrillation (AF) remains unknown. AIM: We sought to evaluate plasma renalase concentration in patients with AF undergoing pulmonary vein isolation (PVI) with respect to AF clinical characteristics, left atrial (LA) remodelling, and PVI efficacy. METHODS: This case-control study included 69 patients (median age 58 years) with either paroxysmal (89%) or persistent (11%) AF, referred for PVI, and a control group consisting of 15 patients without AF, matched for age, sex, and comorbidi-ties. An evaluation of transthoracic echocardiography with LA speckle tracking and plasma renalase concentration using an enzyme-linked immunosorbent assay was performed. AF recurrence was defined as any AF episode on seven-day electro-cardiographic monitoring at six-month follow-up. RESULTS: Renalase level was higher in the study group than in the control group (mean 27.99 vs. 21.48 µg/mL, p = 0.004), but it was lower in patients with persistent AF (19.05 vs. 28.77 µg/mL; p = 0.023) and among patients with AF episodes di-rectly preceding PVI (24.50 vs. 29.66 µg/mL; p = 0.04). Renalase concentration within the first quartile was associated with higher mean heart rate (70 vs. 61 bpm, p = 0.029), greater AF burden (36.9% vs. 9.3%, p = 0.027), greater LA diameter (41.1 vs. 37.9 mm, p = 0.011), and a trend towards less negative global LA strain (-9.4 vs. -13.5, p = 0.082). Logistic regres-sion revealed that global four-chamber LA strain was the only independent predictor of renalase variability (p = 0.0045). Renalase concentration did not predict AF recurrence at six-month follow-up (area under curve [AUC] = 0.614, p = 0.216). CONCLUSIONS: Low renalase level may be associated with impaired rate control, higher AF burden, and advanced LA remodel-ling in AF patients undergoing PVI, but it does not predict sinus rhythm maintenance.

CHA2DS2-Vasc score, age and body mass index as the main risk factors of hyperintense brain lesions in asymptomatic patients with paroxysmal non-valvular atrial fibrillation.

BACKGROUND: The aim was to assess the occurrence, severity and risk factors for silent white matter hyperintensities (WMH) in brain magnetic resonance imaging (MRI) in patients with atrial fibrillation (AF) and to determine the potential relationship between WHM and cognitive decline. METHODS: Seventy-four patients with paroxysmal non-valvular AF were enrolled (age 59 (IQR 50-63)years, males 45/61%). All patients were on adequate warfarin treatment before inclusion and had no history of stroke or TIA. The presence and severity of brain WMH were classified according to the Fazekas scale, while general neurocognitive function was assessed using the Mini-Mental State Examination (MMSE). RESULTS: WMH were found in 51 patients (67.6%; age: 59±7.9years; males: 29/58%). CHADS2-VASc score (OR for 1 point 2.18; 95% CI=1.3-3.65; p=0.003), age (OR for 1year 1.11; 95% CI=1.04-1.18; p=0.001) and BMI (OR for 1kg/m(2) 1.23; 95% CI=1.04-1.45; p=0.017) were independent factors of any brain lesions. A positive correlation between Fazekas scale score and CHA2DS2-VASc score was shown in the entire group (Gamma 0.48; p<0.001). In the group with brain lesions, AF time (p=0.02) and LVEDD (p=0.03) significantly determined the Fazekas scale score (lesions severity). There were no differences in the MMSE score between patients with and without WMH (median: 28 (IQR 27-29) vs 29 (IQR 27.5-30); p=0.2). CONCLUSIONS: Both the presence and severity of brain WMH are related to the CHADS2-VASc score and are not connected with cognitive impairment in this population. Age, BMI, AF time and the indices of heart remodeling constitute important factors influencing brain lesions.

Quality of life in patients with paroxysmal atrial fibrillation after circumferential pulmonary vein ablation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and is associated with a deterioration of quality of life (QoL). Catheter ablation is a therapeutic strategy for some patients with AF. The effectiveness of pulmonary vein isolation is still under assessment. AIM: To assess the long-term influence of circumferential pulmonary vein ablation (CPVA) on QoL in patients with AF. METHODS: The study population consisted of 33 patients (26 males, age 54.2 ± 9 years) with highly symptomatic (EHRA II-III) drug refractory paroxysmal AF, who underwent CPVA. A clinical examination, electrocardiogram (ECG), and Holter ECG were performed before and during a one-year follow-up. The SF-36 Medical Outcomes Survey Short-Form QoL questionnaire, scored on a 0-100 scale for each of eight domains: bodily pain (BP), general health (GH), mental health (MH), physical functioning (PF), role-emotional (RE), role-physical (RP), social functioning (SF), and vitality (V), was collected before and one year after CPVA. RESULTS: In the one-year follow-up 27 (82%) patients were free of AF. EHRA symptoms were improved one-year after CPVA regardless of CPVA efficacy. After the follow-up the SF-36 questionnaire results improved significantly in all of the subscales in patients without a recurrence of AF after CPVA. In subjects with a recurrence of AF, all of the subscales did not indicate any statistically significant differences. There was an association between the CPVA and the following QoL domains: GH (p = 0.018), PF (p = 0.042), and V (p = 0.041). The highest values of the GH and V domains were found in the non-recurrence patients one year after CPVA. CONCLUSIONS: CPVA results in the clinical improvement of patients with symptomatic AF regardless of the final arrhythmia termination. Patients after successful CPVA experienced a significant improvement in all of the subscales of the QoL.

Stroke caused by carotid artery dissection during ablation of atrial arrhythmia.

A 55-year-old woman was admitted to the Cardiology Department due to a poorly tolerated attack of tachyarrhythmia. The patient was enrolled in the electrophysiology study (EPS) study with radiofrequency ablation (RF). After a few applications, during transseptal puncture, the patient demonstrated a neurological syndrome in the form of progressive aphasia and weakness in the right extremities. Computed tomography angiography showed dissection of the left common carotid artery and internal carotid artery with a thrombus within their lumen. Intravenous thrombolytic therapy was initiated, which resulted in an improvement in the patient's neurological status.

Differentiation of arrhythmia originating from the right or left ventricular outflow tract based on the QRS morphology of premature ventricular beats and duration of repolarisation.

BACKGROUND: Premature ventricular beats (PVBs) and monomorphic ventricular tachycardia originating from the right ventricular outflow tract (RVOT) are the most frequent forms of idiopathic ventricular arrhythmias, but arrhythmia originating from the left ventricular outflow tract (LVOT) may be found in about 10% of these patients. AIM: To compare electrocardiographic (ECG) patterns and duration of repolarisation after PVBs originating from the left and right superior part of the interventricular septum which were successfully treated with radiofrequency catheter ablation. METHODS: We studied 62 patients who did not receive antiarrhythmic drug treatment before ablation, including 50 patients with RVOT arrhythmia (21 males, mean age 42 ± 14 years, left ventricular ejection fraction [LVEF] 61 ± 6%) and 12 patients with LVOT arrhythmia (3 males, mean age 41 ± 17 years, LVEF 59 ± 9%). Pre-ablation 24-h Holter ECG recordings were analysed for the total number of PVBs. In addition, we evaluated ectopic beat QRS duration, prematurity index and duration of repolarisation (QT interval, JT interval and TpeakTend values uncorrected for the heart rate) based on ten random daytime PVBs during a period of stable sinus rhythm at a rate of 60-70 bpm. RESULTS: The study groups did not differ by age, LVEF, heart rate and the number of PVBs. RVOT arrhythmia was characterised by a lower prematurity index (0.59 ± 0.11 vs. 0.72 ± 0.09, p = 0.001) and a lower R/S ratio in leads V1-V3 (p < 0.01 for each lead). QRS duration of right-sided PVBs was shorter compared to that of left-sided PVBs (147 ± 13 vs. 166 ± 13 ms, p = 0.002), QT and JT intervals were similar (QT: 422 ± 32 vs. 429 ± 27 ms, p = 0.35; JT: 272 ± 27 vs. 266 ± 27 ms, p = 0.31), and TpeakTend was shorter in RVOT arrhythmia (100 ± 10 vs. 110 ± 6 ms, p = 0.01). Combination of R > S in lead V3 and TpeakTend-PVB > 110 ms identified LVOT arrhythmia with a sensitivity of 75% and specificity of 96%. CONCLUSIONS: Ventricular arrhythmias originating from the left or right superior part of the interventricular septum are not only characterised by different ECG patterns of ventricular ectopic beats but also show significant differences in the repolarisation phase.

[Cognitive dysfunction after cardiac surgery]. / Zaburzenia funkcjonowania poznawczego po zabiegach kardiochirurgicznych.

In spite of the progress in medicine post operative cognitive deficiency (POCD) remains an important clinical problem. Since the introduction of cardiac surgery there have been frequent reports of its adverse neurological outcomes. Recent technological advances have contributed to a lesser occurrence of clinically evident complications such as coma, stroke, epilepsy or blindness. This brought to attention a more common yet occult disorder--POCD. The above malady mostly concerns memory and executive functions. POCD has a negative impact on the quality of life and labor market attachment, however it's relation to mortality seems to be most disturbing. Prevalence of POCD is mainly associated with microembolisms, hipoperfusion and inflammatory reaction of the central nervous system following cardiac surgery. In addition many studies have shown the importance ofbiochemical disorders, cerebral oedema and the influence of comorbidities in the development of POCD. In the light of available evidence, there is no substantial difference between the cognitive outcomes of various types of cardiac surgery. Recent studies show that POCD in this clinical setting is mostly mild and transient. There are, however, patients who suffer from persisting POCD. Modern medicine has not developed standards for treatment of this complication. Setting up methods for prevention, detection and treatment of POCD should be the concern of both physicians and researchers in the following years.

[Acute amnesic syndrome--patient's disorientation baffles a doctor]. / Ostry zespól amnestyczny--dezorientacja chorego zagadka dla lekarza.

We report a 53-year-old female patient who presented a sudden dramatic memory disorder following coronary and cerebral angiography. The patient was disoriented and kept repeating the same questions about time and place. Transient global amnesia was ultimately diagnosed using the Hodges and Warlow criteria. We briefly discuss how to distinguish transient global amnesia from psychogenic amnesia, transient epileptic amnesia and transient ischemic attack.