Search Results (13)

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia associated with left atrial dysfunction. The impact of pulmonary vein isolation (PVI) using pulsed field ablation (PFA) on left atrial function has not been previously quantified. This study aims to evaluate the effects of PVI using PFA on left atrial function in patients with AF. Methods: Thirty-four patients undergoing PVI with PFA between July 2022 and November 2023 were included. The left atrial function was assessed using echocardiography pre-procedure and at 6 months post-procedure. Results: The mean age of the patients was 66.5 ± 9.76 years, with 70.6% being male. The cohort included 44% of patients with paroxysmal AF. PVI was successfully achieved in all patients, with a significant improvement in all aspects of left atrial strain at an average of six-month follow-up. The left atrial strain reservoir (LASr) increased from 12.5 ± 5.8% to 21.7 ± 8.1% (p < 0.001). Notably, patients with paroxysmal AF exhibited a greater increase in LASr compared to those with persistent AF. Additionally, pre-procedural sinus rhythm was a significant predictor of better LASr outcomes. Conclusions: PFA is associated with significant improvement in left atrial reservoir strain, suggesting a positive impact on atrial function. These findings have important implications for the therapeutic management of AF and warrant further research. Full article

Recently, it has been hypothesized that alpha-synuclein protein strain morphology may be associated with clinical subtypes of alpha-synucleinopathies, like Parkinson’s disease and multiple system atrophy. However, direct evidence is lacking due to the caveat of conformation-specific characterization of protein strain morphology. Here we present a new cell model based in vitro method to explore various alpha-synuclein (αsyn) aggregate morphotypes. We performed a spectroscopic investigation of the HEK293 cell model, transfected with human wildtype-αsyn and A53T-αsyn variants, using the amyloid fibril-specific heptameric luminescent oligomeric thiophene h-FTAA. The spectral profile of h-FTAA binding to aggregates displayed a blue-shifted spectrum with a fluorescence decay time longer than in PBS, suggesting a hydrophobic binding site. In vitro spectroscopic binding characterization of h-FTAA with αsyn pre-formed fibrils suggested a binding dissociation constant K_d < 100 nM. The cells expressing the A53T-αsyn and human wildtype-αsyn were exposed to recombinant pre-formed fibrils of human αsyn. The ensuing intracellular aggregates were stained with h-FTAA followed by an evaluation of the spectral features and fluorescence lifetime of intracellular αsyn/h-FTAA, in order to characterize aggregate morphotypes. This study exemplifies the use of cell culture together with conformation-specific ligands to characterize strain morphology by investigating the spectral profiles and fluorescence lifetime of h-FTAA, based upon its binding to a certain αsyn aggregate. This study paves the way for toxicity studies of different αsyn strains in vitro and in vivo. Accurate differentiation of specific alpha-synucleinopathies is still limited to advanced disease stages. However, early subtype-specific diagnosis is of the utmost importance for prognosis and treatment response. The potential association of αsyn aggregates morphotypes detected in biopsies or fluids to disease phenotypes would allow for subtype-specific diagnosis in subclinical disease stage and potentially reveal new subtype-specific treatment targets. Notably, the method may be applied to the entire spectrum of neurodegenerative diseases by using a combination of conformation-specific ligands in a physicochemical environment together with other types of polymorphic amyloid variants and assess the conformation-specific features of various protein pathologies. Full article

Background: To date, only a few studies have evaluated left atrial (LA) mechanics in patients with atrial fibrillation (AF) scheduled for electrical cardioversion (ECV). The present systematic review has been primarily designed to summarize the main findings of these studies and to examine the overall effect of AF on left atrial reservoir strain (LASr) in patients undergoing ECV. Methods: All the echocardiographic studies evaluating the effect of AF on LA mechanics in patients scheduled for ECV, selected from the PubMed and EMBASE databases, were included. There was no limitation of time period. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: The full texts of 12 studies with 880 AF patients were analyzed. The pooled ECV success rate was 91.5% (range 65.8–100%). Over a median follow-up of 5.4 months (range 0.3–12 months), 35.2% of the patients (range 5–68.8%) experienced AF recurrence. At baseline, the average LASr was 11.4% (range 6.2–17.7%). A reduced LASr before ECV was strongly correlated with reduced left atrial appendage (LAA) flow velocities and/or thrombosis. The main independent predictors of cardioversion failure were impaired LASr and previous AF history. A severe LASr deterioration was independently correlated with AF recurrence after ECV. The other independent predictors of AR relapses were LA asynchrony, reduced difference between post- and pre-ECV LASr, and reduced right atrial reservoir strain. Conclusions: LASr assessment before ECV may provide useful prognostic information about AF relapses and improve the refinement of the thromboembolic risk of AF patients scheduled for ECV. Full article

Aims. To identify the difference between adult patients with septal defects and paroxysmal atrial fibrillation (AF) and patients without a history of arrhythmia using the left atrial (LA) volume and function parameters, to reveal the parameters associated with AF development. Methods and results. In this prospective study, 81 patients with septal defects and left-to-right shunts were enrolled between 2021 and 2023 and divided into two groups: with paroxysmal AF and without AF. Left atrial function was analyzed based on the indexed left atrial volumes (LAVI and preA-LAVI), ejection fraction (LAEF), expansion index (LAEI), reservoir (LAS-r), conduit (LAS-cd) and contractile (LAS-ct) strain, and stiffness index (LASI) using a Philips CVx3D ultrasound system (Philips, Amsterdam, The Netherlands) and corresponding software. In total, 26 patients with paroxysmal atrial fibrillation (mean age: 59.6 ± 11.7 years, female: 80.8%) and 55 patients with septal defects without any history of arrhythmias (mean age: 44.8 ± 11.6 years, female: 81.8%) were included. All patients were in the NYHA class I or II at baseline. Our findings demonstrated a significant difference between all LA function parameters in the two groups. Upon univariable analysis, the LAVI, preA-LAVI, LASI, LAEF, LAEI, LAS-r, LAS-c, LAS-ct, age, cardiac index, E/A, and RV pressure were found to be associated with AF. The multivariate analysis identified LAVI (OR 1.236, 95% CI 1.022–1.494, p = 0.03), LAS-r (OR 0.723, 95% CI 0.556–0.940, p = 0.02), and LAS-ct (OR 1.518, 95% CI 1.225–1.880, p < 0.001) as independent predictors of AF development. The proposed model demonstrated high sensitivity and specificity with an adjusted classification threshold of 0.38 (AUC: 0.97, 95% CI 0.93–1.00, sensitivity 92% and specificity 92%, p < 0.001). Conclusions. The assessment of LA function using speckle-tracking echocardiography demonstrated significantly different values in the AF group among patients with congenital septal defects. This technique can therefore be implemented in routine clinical management. The key message. Atrial fibrillation development in adult patients with congenital septal defects and a left-to-right shunt is associated with the changes in left atrial function under conditions of an increased preload. Full article

Pulmonary vein isolation (PVI) with catheter ablation (CA) represents an effective therapy for atrial fibrillation (AF). Unfortunately, it is still not exempt from severe complications. The balance of risks and benefits should be assessed, and a patient-tailored approach is desirable. So far, several clinical and cardiac imaging parameters have been evaluated to investigate pre- and post-procedural features that could help clinicians in the selection of patients at high risk of a poor outcome after CA. This clinical and systematic review analyses the potential role of new LA parameters, such as LA reservoir strain, to predict AF recurrence after CA therapy. Notably, LA reservoir strain gains substantial clinical importance in patients with paroxysmal AF and when a low CHADS2-VASc score is retrieved. LA reservoir strain provides data concerning the risk of AF recurrence after PVI and, thus, in the management of long-term medical therapy in this patient’s group. Full article

The mechanical response of articular cartilage (AC) under compression is anisotropic and depth-dependent. AC is osmotically active, and its intrinsic osmotic swelling pressure is balanced by its collagen fibril network. This mechanism requires the collagen fibers to be under a state of tensile pre-strain. A simple mathematical model is used to explain the depth-dependent strain calculations observed in articular cartilage under 1D axial compression (perpendicular to the articular surface). The collagen fibers are under pre-strain, influenced by proteoglycan concentration (fixed charged density, FCD) and collagen stiffness against swelling stress. The stiffness is introduced in our model as an anisotropic modulus that varies with fibril orientation through tissue depth. The collagen fibers are stiffer to stretching parallel to their length than perpendicular to it; when combined with depth-varying FCD, the model successfully predicts how tissue strains decrease with depth during compression. In summary, this model highlights that the mechanical properties of cartilage depend not only on proteoglycan concentration but also on the intrinsic properties of the pre-strained collagen network. These properties are essential for the proper functioning of articular cartilage. Full article

It has been suggested that cryoballoon (CB) ablation for paroxysmal atrial fibrillation (PAF) may lead to more extensive left atrial (LA) injury than radiofrequency (RF) ablation; however, results are conflicting. We sought to address this issue using modern echocardiographic techniques estimating the LA function after successful CB and RF ablation for PAF. A total of 90 patients (66% males, mean age 57 ± 10 years) successfully treated (no AF recurrences confirmed in serial 4–7 day ECG Holter monitoring) with RF (51%) or CB (49%) ablation for PAF were retrospectively studied. Echocardiography with speckle tracking (STE) was performed before and 12 months after the procedure. The peak longitudinal LA strain (LAS) and strain rate (LASR) during the reservoir (r), conduit (cd), and contraction (ct) phases were measured in sinus rhythm. Analysis of covariance was applied to compare changes in the echocardiographic parameters over time with the baseline measurements as covariance and the type of ablation as the factor. The parallelism of the slopes of the covariance was tested. The LA diameter decreased (38.3 ± 4.1 mm vs. 36.8 ± 3.6 mm, p < 0.001) in the whole study group at 12 months after ablation. The LASRr and LASRcd increased (1.1 ± 0.3 s⁻¹ vs. 1.3 ± 0.3 s⁻¹, p < 0.001 and 1.1 ± 0.3 s⁻¹ vs. 1.2 ± 0.3 s⁻¹, p < 0.001, respectively) whereas other LA strain parameters remained unchanged in the whole study group at 12 months after ablation. In the analysis of LA function at 12 months after the procedure regarding the mode of ablation, the worsening of parameters reflecting LA compliance was observed in patients with better pre-served baseline values in the CB ablation subgroup. For baseline LAScd >28%, the difference ΔCB − ΔRF was −7.6 (11.7; −3.4), p < 0.001, and for baseline LAScd >16%, ΔCB − ΔRF was −1.8 (−3.2; −0.4), p = 0.014. The traditional Doppler-derived parameter e′ showed the same trend—for baseline e′ ≥12 cm/s, ΔCB − ΔRF was −1.7 (−2.8; −0.6), p = 0.003. We conclude that worsening of parameters reflecting LA compliance was observed 12 months after CB ablation compared to RF ablation for PAF in patients who underwent a successful procedure and had better-preserved baseline LA function. This might suggest subclinical dysfunction of LA after the CB ablation procedure. The clinical significance of these findings warrants further investigations. Full article

Cardiovascular disease and cancer coexist and lead to exertional dyspnea. The aim of the study was to determine the prognostic significance of cardiac comorbidities, ECG and baseline echocardiography in lung cancer patients with varying degrees of reduced performance status. This prospective study included 104 patients with histopathologically confirmed lung cancer, pre-qualified for systemic treatment due to metastatic or locally advanced malignancy but not eligible for thoracic surgery. The patients underwent a comprehensive cardio-oncological evaluation. Overall survival negative predictors included low ECOG 2 (Eastern Cooperative Oncology Group) performance status, stage IV (bone or liver/adrenal metastases in particular), pleural effusion, the use of analgesics and among cardiac factors, two ECG parameters: atrial fibrillation (HR = 2.39) and heart rate >90/min (HR = 1.67). Among echocardiographic parameters, RVSP > 39 mmHg was a negative predictor (HR = 2.01), while RVSP < 21 mmHg and RV free wall strain < −30% were positive predictors (HR = 0.36 and HR = 0.56, respectively), whereas RV GLS < −25.5% had a borderline significance (HR = 0.59; p = 0.05). Logistical regression analysis showed ECOG = 2 significantly correlated with the following echocardiographic parameters: increasing RVSP, RV GLS, RV free wall strain and decreasing ACT, FAC (p < 0.05). Selected echocardiographic parameters may be helpful in predicting poor performance in lung cancer patients and, supplemented with ECG evaluation, broaden the possibilities of prognostic evaluation. Full article

The distinct neuropathological features of the different α-Synucleinopathies, as well as the diversity of the α-Synuclein (α-Syn) intracellular inclusion bodies observed in post mortem brain sections, are thought to reflect the strain diversity characterizing invasive α-Syn amyloids. However, this “one strain, one disease” view is still hypothetical, and to date, a possible disease-specific contribution of non-amyloid factors has not been ruled out. In Multiple System Atrophy (MSA), the buildup of α-Syn inclusions in oligodendrocytes seems to result from the terminal storage of α-Syn amyloid aggregates first pre-assembled in neurons. This assembly occurs at the level of neuronal cytoplasmic inclusions, and even earlier, within neuronal intranuclear inclusions (NIIs). Intriguingly, α-Syn NIIs are never observed in α-Synucleinopathies other than MSA, suggesting that these inclusions originate (i) from the unique molecular properties of the α-Syn fibril strains encountered in this disease, or alternatively, (ii) from other factors specifically dysregulated in MSA and driving the intranuclear fibrillization of α-Syn. We report the isolation and structural characterization of a synthetic human α-Syn fibril strain uniquely capable of seeding α-Syn fibrillization inside the nuclear compartment. In primary mouse cortical neurons, this strain provokes the buildup of NIIs with a remarkable morphology reminiscent of cat’s eye marbles (see video abstract). These α-Syn inclusions form giant patterns made of one, two, or three lentiform beams that span the whole intranuclear volume, pushing apart the chromatin. The input fibrils are no longer detectable inside the NIIs, where they become dominated by the aggregation of endogenous α-Syn. In addition to its phosphorylation at S129, α-Syn forming the NIIs acquires an epitope antibody reactivity profile that indicates its organization into fibrils, and is associated with the classical markers of α-Syn pathology p62 and ubiquitin. NIIs are also observed in vivo after intracerebral injection of the fibril strain in mice. Our data thus show that the ability to seed NIIs is a strain property that is integrally encoded in the fibril supramolecular architecture. Upstream alterations of cellular mechanisms are not required. In contrast to the lentiform TDP-43 NIIs, which are observed in certain frontotemporal dementias and which are conditional upon GRN or VCP mutations, our data support the hypothesis that the presence of α-Syn NIIs in MSA is instead purely amyloid-strain-dependent. Full article

Fibrotic scarring is prevalent in a range of collagenous tissue disorders. Understanding the role of matrix biophysics in contributing to fibrotic progression is important to develop therapies, as well as to elucidate biological mechanisms. Here, we demonstrate how microfocus small-angle X-ray scattering (SAXS), with in situ mechanics and correlative imaging, can provide quantitative and position-resolved information on the fibrotic matrix nanostructure and its mechanical properties. We use as an example the case of keloid scarring in skin. SAXS mapping reveals heterogeneous gradients in collagen fibrillar concentration, fibril pre-strain (variations in D-period) and a new interfibrillar component likely linked to proteoglycans, indicating evidence of a complex 3D structure at the nanoscale. Furthermore, we demonstrate a proof-of-principle for a diffraction-contrast correlative imaging technique, incorporating, for the first time, DIC and SAXS, and providing an initial estimate for measuring spatially resolved fibrillar-level strain and reorientation in such heterogeneous tissues. By application of the method, we quantify (at the microscale) fibrillar reorientations, increases in fibrillar D-period variance, and increases in mean D-period under macroscopic tissue strains of ~20%. Our results open the opportunity of using synchrotron X-ray nanomechanical imaging as a quantitative tool to probe structure–function relations in keloid and other fibrotic disorders in situ. Full article

Aims: Tachyarrhythmia due to atrial fibrillation (AF) is often associated with reduced left ventricular (LV) function and has been proposed to cause arrhythmia-induced cardiomyopathy (AIC). However, the precise diagnostics of AIC and reversibility after rhythm restoration are poorly understood. Our aim was to investigate systolic LV function in tachycardic AF and to evaluate the direct effect of rhythm restoration. Methods: We prospectively studied 24 patients (71% male, age 65 ± 9 years) with tachycardic AF and newly diagnosed reduced left ventricular ejection fraction (LVEF). Just before and immediately after electrical cardioversion (ECV), transthoracic echocardiography was performed. Geometric as well as functional data were assessed. Results: Patients presented with a heart rate (HR) of 117.4 ± 21.6/min and a 2D-/3D-LVEF of 32 ± 9/31 ± 8%. ECV to sinus rhythm normalized HR to 77 ± 11/min with an increase of 2D-/3D-LVEF to 37 ± 9/37 ± 10% (p < 0.01 vs. baseline, each). Left ventricular geometry changed with an increase of end-diastolic volume (LVEDV) while end-systolic volume (LVESV) remained unchanged. Parameters concerning myocardial deformation (global longitudinal strain (GLS), strain rate (SR)) decreased whereas the RR interval-corrected GLS (GLSc) remained unchanged. In a simple linear regression model, GLS correlated with 2D- and 3D-LVEF not only before (pre) ECV, but also after (post) ECV. We demonstrate that the increase of LVEF and GLS (ratios pre/post) correlates with the change of HR (ΔHR; R² = 0.20, 0.33 and 0.32, p < 0.05 each), whereas ratios of GLSc and SR do not significantly correlate with HR (R² = 0.03 and 0.01, p = n.s. each). Conclusion: In patients with tachyarrhythmia and reduced ejection fraction, ECV leads to immediate improvement in EF and GLS while HR-corrected LV contractility remains unchanged. This suggests that the immediate effects of rhythm restoration are mostly related to changes in left ventricular volume, but not to an acute improvement of heart-rate independent contractility. Full article

Water hyacinth is a rapidly growing troublesome aquatic weed plant, which causes eutrophication in water bodies and irreversible damage to the ecological system. In this work, we have investigated the water hyacinth biomass (WHB) hydrolysis efficacy of dilute alkaline (DA) pretreatment followed by biological pretreatment with white-rot fungus Alternaria alternata strain AKJK-2. The effectiveness of the dilute alkaline (DA) and biological pretreatment process on WHB was confirmed by using X-ray Diffraction (XRD) and Fourier Transform Infrared Spectrophotometer (FTIR), and was further visualized by Scanning Electron Microscope (SEM) and Confocal Laser Scanning Microscopy (CLSM). XRD spectra showed the increase in the crystallinity of pretreated samples, attributed to the elimination of amorphous components as lignin and hemicellulose. FTIR peak analysis of pre-treated WHB showed substantial changes in the absorption of cellulose functional groups and the elimination of lignin signals. Scanning electron microscopy (SEM) images showed firm, compact, highly ordered, and rigid fibril structures without degradation in the untreated WHB sample, while the pretreated samples exhibited loose, dispersed, and distorted structures. XRD indices (Segal, Landis, and Faneite), and FTIR indices [Hydrogen bond intensity (HBI); Total crystallinity index (TCI); and Lateral order crystallinity (LOI)] results were similar to the aforementioned results, and also showed an increase in the crystallinity both in alkaline and biological pretreatments. Alkaline pretreated WHB, with these indices, also showed the highest crystallinity and a crystalline allomorphs mixture of cellulose I (native) and cellulose II. These results were further validated by the CLSM, wherein fluorescent signals were lost after the pretreatment of WHB over control. Overall, these findings showed the significant potential of integrated assessment tools with chemical and biological pretreatment for large-scale utilization and bioconversion of this potential aquatic weed for bioenergy production. Full article

Although some strains of Leptothrix spp. isolated from aquatic environments have been characterized by culturing them in laboratory conditions, they often show morphological and chemical features distinct from those found in natural environments. To resolve this discrepancy, a novel cultivation method was devised for culturing such strains in natural groundwater. Leptothrix sp. strain OUMS1 was pre-cultured in a medium lacking Fe for 2 days, and then injected into a small dialysis tube bag and immersed in a container with continuously flowing groundwater for 1–3 and 14 days. Microscopic analysis of the initial phase of sheath formation and arbitrary comparisons with medium cultures revealed that in groundwater the surface coat of the sheath comprised much thinner fibrils, and an inner sheath wall that was much thinner and more indistinct compared with medium cultures. These differences were probably attributable to poorer secretion from the cell surface in groundwater conditions. A nutrient-rich medium likely activates cell metabolism and promotes secretion, resulting in a thicker inner sheath wall and thicker outer coat fibrils. Aqueous-phase Fe was deposited on immature sheaths in a similar manner in both cultures. These results indicate that laboratory culture of isolated microbes does not always reflect their characteristics in natural environments. Full article