Insights into RC time curve fit analysis of pulmonary artery pressure decay.

The notion of a constant relationship between resistance and capacitance (RC time) in the pulmonary circulation has been challenged by more recent research. The RC time can be obtained using either a simplified empirical approach or a semilogarithmic equation. Although direct curve-fit analysis is a feasible and ostensibly reference approach for RC analysis, it remains largely unexplored. We aimed to study the relationship between various RC methods in different states of pulmonary hemodynamics. Methods In total, 182 patients underwent clinically indicated right heart catheterization. The pressure curves were exported and processed using the MATLAB software. We calculated the RC time using the empirical method (RCEST), semilogarithmic approach (RCSL), and direct measurement of curve fit (RCFIT). Results Among 182 patients, 137 had pulmonary hypertension due to left heart disease (PH-LHD), 35 had pulmonary arterial hypertension (PAH), and 10 demonstrated normal hemodynamics (non-PH). RCEST consistently overestimated the RCFIT and RCSL measurements by a mean of 75%. With all three methods, the RC values were longer in the PAH (RCFIT = 0.36 ± 0.14 s) than in the PH-LHD (0.27 ± 0.1 s) and non-PH (0.27 ± 0.09 s) groups (p < 0.001). Although the RCSL and RCFIT values were similar among the three subgroups, they exhibited broad limits of agreement. Finally, the RCEST demonstrated a strong discriminatory ability (AUC = 0.86, p < 0.001, CI = 0.79-0.93) in identifying PAH. Conclusion RC time in PAH patients was substantially prolonged compared to that in PH-LHD and non-PH patients. The use of the empirical formula yielded systematic RC overestimation. In contrast, the semilogarithmic analysis provided reliable RC estimates, particularly for group comparisons.

Association of Left Atrial Appendage Morphology and Function With Stroke and Transient Ischemic Attack in Atrial Fibrillation Patients.

We aimed to correlate left atrial appendage (LAA) structure and function with the history of stroke/transient ischemic attack (TIA) in patients with atrial fibrillation (AF). We analyzed the data of 649 patients with AF who were scheduled for catheter ablation. Patients underwent cardiac computed tomography and transesophageal echocardiography before ablation. The LAA morphologies depicted by cardiac computed tomography were categorized into 4 groups: cauliflower, chicken wing, swan, and windsock shapes. The mean age was 61.3 ± 10.5 years, 33.9% were women. The prevalence of stroke/TIA was 7.1%. After adjustment for the main risk factors, the LAA flow velocity ≤35.3 cm/s (odds ratio [OR] 2.18, 95% confidence interval [CI] 1.09 to 4.61, p = 0.033) and the swan LAA shape (OR 2.69, 95% CI 0.96 to 6.86, p = 0.047) independently associated with a higher risk of stroke/TIA, whereas the windsock LAA morphology proved to be protective (OR 0.32, 95% CI 0.12 to 0.77, p = 0.017) compared with the cauliflower LAA shape. Comparing the differences between the LAA morphology groups, we measured a significantly smaller LAA orifice area (389.3 ± 137.7 mm2 in windsock vs 428.3 ± 158.9 ml in cauliflower, p = 0.021) and LAA volume (7.4 ± 3.0 mm2 in windsock vs 8.5 ± 4.8 mm2 in cauliflower, p = 0.012) in patients with windsock LAA morphology, whereas the LAA flow velocity did not differ significantly. Reduced LAA function and swan LAA morphology were independently associated with a higher prevalence of stroke/TIA, whereas the windsock LAA shape proved to be protective. Comparing the differences between the various LAA morphology types, significantly lower LAA volume and LAA orifice area were measured in the windsock LAA shape than in the cauliflower LAA shape.

Prediction of gastroesophageal reflux episodes by smooth muscle electromyography: A translational study in rats and adolescents.

Aims: Our aim was to measure the myoelectric modifications during gastric acid secretion along with the gastric pH in a rat model and to detect the gastrointestinal (GI) myoelectric changes in adolescents suffering from gastroesophageal reflux disease (GERD) along with the esophageal pH measurement. Main methods: In anesthetized rats, gastric acid secretion was initiated with intragastric histamine (50 mg/kg), and gastric pH, GI myoelectric activity and mechanical GI contractions were measured with intragastric pH electrode, subcutaneously implanted smooth muscle electromyography (SMEMG) electrodes and organ implanted strain gauges, respectively. In the clinical study, esophageal pH and GI myoelectric activity were measured in adolescents suffering from GERD with intraesophageal pH electrode and SMEMG electrodes placed on the abdominal surface, respectively. The SMEMG records were analyzed by fast Fourier transformation (FFT) and power spectrum density maximum (PsDmax) values were calculated for the GI segments. Key findings: In rats, histamine initiated an immediate increase in gastric PsDmax, which preceded the significant reduction in gastric pH by 75 min. The myoelectric change was independent of mechanical GI contractions. In adolescents, the GERD episodes were preceded by a significant increase in gastric PsDmax 45 min earlier. These changes were independent of motion or meals. Significance: Increased gastric myoelectric activity during histamine stimulation or GERD might be linked to the enhanced activity of the gastric proton pump, indicating a link between gastric acid secretion and GERD episodes. It is supposed that SMEMG might be a tool for predicting forthcoming reflux episodes in GERD.

Use of a new non-contrast-enhanced BOOST cardiac MR sequence before electrical cardioversion or ablation of atrial fibrillation-a pilot study.

Introduction: Left atrial appendage (LAA) thrombus is the most common source of embolization in atrial fibrillation (AF). Transesophageal echocardiography (TEE) is the gold standard method for LAA thrombus exclusion. Our pilot study aimed to compare the efficacy of a new non-contrast-enhanced cardiac magnetic resonance (CMR) sequence (BOOST) with TEE for the detection of LAA thrombus and to evaluate the usefulness of BOOST images for planning radiofrequency catheter ablation (RFCA) compared with left atrial (LA) contrast-enhanced computed tomography (CT). We also attempted to assess the patients' subjective experiences with TEE and CMR. Methods: Patients with AF undergoing either electrical cardioversion or RFCA were enrolled. Participants underwent pre-procedural TEE and CMR scans to evaluate LAA thrombus status and pulmonary vein anatomy. Patient experiences with TEE and CMR were assessed using a questionnaire developed by our team. Some patients scheduled for RFCA also had pre-procedural LA contrast-enhanced CT. In such cases, the operating physician was asked to subjectively define the quality of the CT and CMR scan on a scale of 1-10 (1 = worst, 10 = best) and comment on CMR's usefulness in RFCA planning. Results: Seventy-one patients were enrolled. In 94.4%, both TEE and CMR excluded, and in 1 patient, both modalities reported the presence of LAA thrombus. In 1 patient, TEE was inconclusive, but CMR excluded LAA thrombus. In 2 patients, CMR could not exclude the presence of thrombus, but in 1 of those cases, TEE was also indecisive. During TEE, 67%, during CMR, only 1.9% of patients reported pain (p < 0.0001), and 89% would prefer CMR in case of a repeat examination. The quality of the left atrial contrast-enhanced CT scans was better compared with the image quality of the CMR BOOST sequence [8 (7-9) vs. 6 (5-7), p < 0.0001]. Still, the CMR images were useful for procedural planning in 91% of cases. Conclusion: The new CMR BOOST sequence provides appropriate image quality for ablation planning. The sequence might be useful for excluding larger LAA thrombi; however, its accuracy in detecting smaller thrombi is limited. Most patients preferred CMR over TEE in this indication.

Rab26 controls secretory granule maturation and breakdown in Drosophila.

At the onset of Drosophila metamorphosis, plenty of secretory glue granules are released from salivary gland cells and the glue is deposited on the ventral side of the forming (pre)pupa to attach it to a dry surface. Prior to this, a poorly understood maturation process takes place during which secretory granules gradually grow via homotypic fusions, and their contents are reorganized. Here we show that the small GTPase Rab26 localizes to immature (smaller, non-acidic) glue granules and its presence prevents vesicle acidification. Rab26 mutation accelerates the maturation, acidification and release of these secretory vesicles as well as the lysosomal breakdown (crinophagy) of residual, non-released glue granules. Strikingly, loss of Mon1, an activator of the late endosomal and lysosomal fusion factor Rab7, results in Rab26 remaining associated even with the large glue granules and a concomitant defect in glue release, similar to the effects of Rab26 overexpression. Our data thus identify Rab26 as a key regulator of secretory vesicle maturation that promotes early steps (vesicle growth) and inhibits later steps (lysosomal transport, acidification, content reorganization, release, and breakdown), which is counteracted by Mon1.

Admission risk factors and predictors of moderate or severe pediatric acute pancreatitis: A systematic review and meta-analysis.

Introduction: Pediatric acute pancreatitis (PAP) has an increasing incidence and is now estimated to be almost as common as in adults. Up to 30% of patients with PAP will develop moderate or severe disease course (M/SPAP), characterized by organ failure, local or systemic complications. There is still no consensus regarding on-admission severity prediction in these patients. Our aim was to conduct a systematic review and meta-analysis of available predictive score systems and parameters, and differences between on-admission parameters in mild and M/SPAP. Methods: We conducted a systematic search on the 14th February, 2022 in MEDLINE, Embase and CENTRAL. We performed random-effects meta-analysis of on-admission differences between mild and M/SPAP in laboratory parameters, etiology, demographic factors, etc. calculating risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI) and created forest plots. For the meta-analysis of predictive score systems, we generated hierarchical summary receiver operating characteristic curves using a bivariate model. Chi-squared tests were performed and I2 values calculated to assess statistical heterogeneity. Results: We included 44 studies - mostly retrospective cohorts - in our review. Among predictive score systems examined by at least 5 studies, the modified Glasgow scale had the highest specificity (91.5% for values ≥3), and the Pediatric Acute Pancreatitis Severity score the highest sensitivity (63.1% for values ≥3). The performance of other proposed score systems and values were summarized. Traumatic (RR: 1.70 95% CI: 1.09-2.67) and drug-induced (RR: 1.33 95% CI: 0.98-1.87) etiologies were associated with a higher rate of M/SPAP, while anatomical (RR: 0.6195% CI: 0.38-0.96) and biliary (RR: 0.72 95% CI: 0.53-0.99) PAP tended to be less severe. Discussion: Many predictive score systems were proposed to assess the possibility of M/SPAP course. The most commonly used ones exhibit good specificity, but subpar sensitivity. Our systematic review provides a rigorous overview of predictive options assessed thus far, that can serve as a basis for future improvement of scores via the addition of parameters with a better observed sensitivity: e.g., lipase exceeding 7-times the upper threshold, hemoglobin, etc. The addition of etiological factors is another possibility, as they can herald a more severe disease course. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=307271, PROSPERO, identifier: CRD42022307271.

Predictors and neurological consequences of periprocedural cerebrovascular events following transcatheter aortic valve implantation with self-expanding valves.

Aims: To evaluate the patient- and procedure-related predictors of transcatheter aortic-valve implantation (TAVI)-associated ischemic brain lesions and to assess the effect of silent cerebral ischemic lesions (SCIL) on neurocognitive function. Methods and results: We investigated 113 consecutive patients with severe aortic stenosis who underwent brain magnetic resonance imaging (MRI) within a week following TAVI. To assess periprocedural cerebral ischemic lesions, diffusion-weighted MRI was utilized. We used multivariate linear regression to identify the independent predictors of TAVI-related ischemic lesion volume (ILV) and periprocedural stroke. Neurocognitive evaluation was performed before and following TAVI at 6-month and one-year follow-up. Following TAVI, a total of 944 new cerebral ischemic lesions were detected in 104 patients (92%). The median ILV was 257 µl (interquartile range [IQR]:97.1-718.8µl) with a median lesion number of 6/patient [IQR:2-10]. The majority of ischemic lesions were clinically silent (95%), while 5% of the lesions induced a stroke, which was confirmed by MRI. Predilatation (ß = 1.13[95%CI:0.32-1.93], p = 0.01) and the number of valve positioning attempts during implantation (ß = 0.28[95%CI:0.06-0.50], p = 0.02) increased the log-transformed total ILV. Predilatation (OR = 12.04[95%CI:1.46-99.07], p = 0.02) and alternative access routes (OR = 7.84[95%CI:1.01-61.07], p = 0.02) were associated with stroke after adjustments for comorbidities and periprocedural factors. The presence of SCILs were not associated with a change in neurocognitive function that remained stable during the one-year follow-up. Conclusion: While periprocedural ischemic lesions are frequent, most of them are clinically silent and might not impact the patients' neurocognitive function. The number of valve positioning attempts, predilatation, and alternative access routes should be taken into consideration during TAVI to reduce the ILV and risk for stroke.

Ecdysone receptor isoform specific regulation of secretory granule acidification in the larval Drosophila salivary gland.

Bulk production and release of glue containing secretory granules takes place in the larval salivary gland during Drosophila development in order to attach the metamorphosing animal to a dry surface. These granules undergo a maturation process to prepare glue for exocytosis, which includes homotypic fusions to increase the size of granules, vesicle acidification and ion uptake. The steroid hormone 20-hydroxyecdysone is known to be required for the first and last steps of this process: glue synthesis and secretion, respectively. Here we show that the B1 isoform of Ecdysone receptor (EcR), together with its binding partner Ultraspiracle, are also necessary for the maturation of glue granules by promoting their acidification via regulation of Vha55 expression, which encodes an essential subunit of the V-ATPase proton pump. This is antagonized by the EcR-A isoform, overexpression of which decreases EcR-B1 and Vha55 expression and glue granule acidification. Our data shed light on a previously unknown, ecdysone receptor isoform-specific regulation of glue granule maturation.

Subclinical leaflet thrombosis after transcatheter aortic valve implantation is associated with silent brain injury on brain magnetic resonance imaging.

AIMS: Whether hypoattenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) carries a risk of subclinical brain injury (SBI) is unknown. We investigated whether HALT is associated with SBI detected on magnetic resonance imaging (MRI), and whether post-TAVI SBI impacts the patients' cognition and outcome. METHODS AND RESULTS: We prospectively enrolled 153 patients (age: 78.1 ± 6.3 years; female 44%) who underwent TAVI. Brain MRI was performed shortly post-TAVI and 6 months later to assess the occurrence of acute silent cerebral ischaemic lesions (SCIL) and chronic white matter hyperintensities (WMH). HALT was screened by cardiac computed tomography (CT) angiography (CTA) 6 months post-TAVI. Neurocognitive evaluation was performed before, shortly after and 6 months following TAVI. At 6 months, 115 patients had diagnostic CTA and 10 had HALT. HALT status, baseline, and follow-up MRIs were available in 91 cases. At 6 months, new SCIL was evident in 16%, new WMH in 66%. New WMH was more frequent (100 vs. 62%; P = 0.047) with higher median volume (319 vs. 50 mm3; P = 0.039) among HALT-patients. In uni- and multivariate analysis, HALT was associated with new WMH volume (beta: 0.72; 95%CI: 0.2-1.39; P = 0.009). The patients' cognitive trajectory from pre-TAVI to 6 months showed significant association with the 6-month SCIL volume (beta: -4.69; 95%CI: -9.13 to 0.27; P = 0.038), but was not related to the presence or volume of new WMH. During a 3.1-year follow-up, neither HALT [hazard ratio (HR): 0.86; 95%CI: 0.202-3.687; P = 0.84], nor the related WMH burden (HR: 1.09; 95%CI: 0.701-1.680; P = 0.71) was related with increased mortality. CONCLUSIONS: At 6 months post-TAVI, HALT was linked with greater WMH burden, but did not carry an increased risk of cognitive decline or mortality over a 3.1-year follow-up (NCT02826200).

Microstructural alterations measured by diffusion tensor imaging following transcatheter aortic valve replacement and their association with cerebral ischemic injury and cognitive function - a prospective study.

PURPOSE: We assessed diffusion tensor imaging (DTI) metric changes of the corpus callosum and cingulum correlated to postprocedural ischemic lesion load (ILL) and cognitive performance in transcatheter aortic valve replacement (TAVR). METHODS: TAVR subjects had DTI post-TAVR (≤ 8 days) and at 6 months (78 participants, males 56%, age 78.8 years ± 6.3) and four neurocognitive tests (pre-TAVR, post-TAVR, 6 months, 1 year). DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD)) were calculated for 7 regions: corpus callosum (genu, body, splenium) and cingulum (cingulate gyrus, parahippocampal cingulum bilaterally). DTI metrics post-TAVR and at 6 months were compared with Student's t-test (p < 0.0071) and ANOVA covarying for sex, ILL (p < 0.05) with post hoc analysis of ILL groups (p < 0.0167). Repeated-measures linear mixed-effect model (p < 0.05) was performed to investigate the effect of time and ILL on cognition. RESULTS: At 6 months, significant decrease of the following DTI metrics was detected: AD (genu, body, splenium, right parahippocampal cingulum: p ≤ 0.0046); MD (body, both cingulate gyri: p ≤ 0.0050); RD (left cingulate gyrus: p = 0.0021); FA (splenium: p < 0.0001). ANOVA confirmed significant effect of female sex on AD + MD reduction (body, right cingulate gyrus) and AD reduction (left cingulate gyrus) (p ≤ 0.0254). Significant negative effect of ILL on some DTI metric changes was found (AD + MD-body: p ≤ 0.0050; MD-left cingulate gyrus: p = 0.0087). Cognitive performance remained stable with significant negative correlation of ILL and retrograde memory and visual scores (p ≤ 0.0483). CONCLUSION: Significant effect of TAVR on cerebral microstructural integrity was found with reduced diffusivities opposite to the trends reported in various neurodegenerative conditions/ageing, notably in women and lower ILL, and with preserved/improved cognition. TRIAL REGISTRATION NUMBER: NCT02826200 at ClinicalTrials.gov; date of registration: 07. July 2016.

Cardiac Amyloidosis with Normal Wall Thickness: Prevalence, Clinical Characteristics and Outcome in a Retrospective Analysis.

Background: Cardiac amyloidosis (CA) is a rare, progressive, infiltrative cardiac disease. Light chain (AL) and transthyretin (ATTR) amyloidosis are in the background in almost all cases. New, easily available diagnostic tools and recently introduced novel therapies for both types of CA put this disease into the field of interest. Increased left ventricular wall thickness (IWT) detected by echocardiography is generally thought to be a necessary part of the diagnosis. We aimed to determine the proportion of CA patients without IWT, and to define the clinical characteristics of this cohort. Methods: In an academic tertiary center for CA, we identified patients diagnosed and treated for CA between January 2009 and February 2022. In a retrospective analysis we defined the proportion of patients with (≥12 mm) and without (<12 mm) IWT, and described their clinical features. Results: We identified 98 patients suitable for the analysis. In total, 70 had AL and 27 ATTR CA; 89 patients had CA with IWT and 9 patients (9%) had CA without IWT. All non-IWT patients had AL type CA. Both group of patients had clinically significant disease, which is supported by the relevant elevation in cardiac biomarker levels. There was no difference between the outcome of the two groups. Conclusion: Patients without IWT form a relevant subgroup among those with CA. Our results suggest that diagnostic algorithms and criteria should take these individuals into consideration, and, therefore, give them access to effective treatments.

Selective autophagy and Golgi quality control in <i>Drosophila</i>.

The LIR motif-docking site (LDS) of Atg8/LC3 proteins is essential for the binding of LC3-interacting region (LIR)-containing proteins and their subsequent degradation by macroautophagy/autophagy. In our recent study, we created a mutated LDS site in Atg8a, the <i>Drosophila</i> homolog of Atg8/LC3 and found that LDS mutants accumulate known autophagy substrates and have reduced lifespan. We also conducted quantitative proteomics analyses and identified several proteins that are enriched in the LDS mutants, including Gmap (Golgi microtubule-associated protein). Gmap contains a LIR motif and accumulates in LDS mutants. We showed that Gmap and Atg8a interact in a LIR-LDS dependent manner and that the Golgi size and morphology are altered in Atg8a-LDS and Gmap-LIR motif mutants. Our findings highlight a role for Gmap in the regulation of Golgiphagy.

GMAP is an Atg8a-interacting protein that regulates Golgi turnover in Drosophila.

Selective autophagy receptors and adapters contain short linear motifs called LIR motifs (LC3-interacting region), which are required for the interaction with the Atg8-family proteins. LIR motifs bind to the hydrophobic pockets of the LIR motif docking site (LDS) of the respective Atg8-family proteins. The physiological significance of LDS docking sites has not been clarified in vivo. Here, we show that Atg8a-LDS mutant Drosophila flies accumulate autophagy substrates and have reduced lifespan. Using quantitative proteomics to identify the proteins that accumulate in Atg8a-LDS mutants, we identify the cis-Golgi protein GMAP (Golgi microtubule-associated protein) as a LIR motif-containing protein that interacts with Atg8a. GMAP LIR mutant flies exhibit accumulation of Golgi markers and elongated Golgi morphology. Our data suggest that GMAP mediates the turnover of Golgi by selective autophagy to regulate its morphology and size via its LIR motif-mediated interaction with Atg8a.

Multidisciplinary management of patients affected with pseudoxanthoma elasticum / Pseudoxanthoma elasticumban szenvedo betegek multidiszciplináris ellátása

Pseudoxanthoma elasticum (PXE, OMIM # 264800) is an autosomal recessive, multisystemic disorder, associated with mutations of the ABCC6 gene. Ectopic mineralization is in the background of the clinical manifestations of the disease. Calcium-salt crystals are deposited primarily in the skin, in the Bruch membrane of the eyes, and in the vascular endothelium. Thus, in addition to the skin lesions, visual impairment and cardiovascular involvement also occur. Clinical symptoms show varying severity and display heterogeneous appearance. The identification of the phenotype and care of the patients require a multidisciplinary perspective based on the collaboration of a dermatologist, ophthalmologist, cardiologist, and clinical geneticist. The aim of our work is to describe the development of symptoms of the disease, in order to facilitate the diagnosis. In addition, we aim to draw attention to the importance of early diagnosis of pseudoxanthoma elasticum, and to present modern diagnostic methods. Considering the development of severe systemic complications, the early diagnosis with the collaboration between related specialists is crucial to provide optimal clinical care and management of the patients.

The Predictive Value of Left Atrial Strain Following Transcatheter Aortic Valve Implantation on Anatomical and Functional Reverse Remodeling in a Multi-Modality Study.

Introduction: Transcatheter aortic valve implantation (TAVI) can improve left ventricular (LV) mechanics and survival. Data on the predictive value of left atrial (LA) strain following TAVI are scarce. We aimed to evaluate the association of LA strain measured shortly post-TAVI with functional and anatomical reverse remodeling of the LA and LV, and its association with mortality. Methods: We prospectively investigated 90 patients who underwent TAVI. Transthoracic echocardiography including strain analysis was performed shortly after TAVI and repeated 6 months later. CT angiography (CTA) was performed for pre-TAVI planning and 6 months post-TAVI. Speckle tracking echocardiography was used to determine LA peak reservoir strain (LASr) and LV global longitudinal strain (LV-GL), LA volume index (LAVi) was measured by TTE. LV mass index (LVMi) was calculated using CTA images. LA reverse remodeling was based on LASr and LAVi changes, whereas LV reverse remodeling was defined as an improvement in LV-GLS or a reduction of LVMi. The association of severely reduced LASr (<20%) at baseline with changes (Δ) in LASr, LAVi, LV-GLS and LVMi were analyzed using linear regression, and Cox proportional hazard model for mortality. Results: Mean LASr and LV-GLS were 17.7 ± 8.4 and -15.3 ± 3.4% at baseline and 20.2 ± 10.2 and -16.6 ± 4.0% at follow-up (p = 0.024 and p < 0.001, respectively). Severely reduced LASr at baseline was associated with more pronounced ΔLASr (ß = 5.24, p = 0.025) and LVMi reduction on follow-up (ß = 5.78, p = 0.036), however, the majority of the patients had <20% LASr on follow-up (44.4%). Also, ΔLASr was associated with ΔLV-GLS (adjusted ß = 2.10, p < 0.001). No significant difference in survival was found between patients with baseline severely reduced LASr (<20%) and higher LASr (≥20%) (p = 0.054). Conclusion: LV reverse remodeling based on LVMi was present even in patients with severely reduced LASr following TAVI, although extensive LA damage based on LA strain was demonstrated by its limited improvement over time. Clinical Trial Registration: (ClinicalTrials.gov number: NCT02826200).

Fibrin to von Willebrand factor ratio in arterial thrombi is associated with plasma levels of inflammatory biomarkers and local abundance of extracellular DNA.

INTRODUCTION: The composition of thrombi determines their structure, mechanical stability, susceptibility to lysis, and consequently, the clinical outcome in coronary artery disease (CAD), acute ischemic stroke (AIS), and peripheral artery disease (PAD). Fibrin forms the primary matrix of thrombi intertwined with DNA, derived from neutrophil extracellular traps (NETs), and von Willebrand factor (VWF) bridging DNA and platelets. Here we examined the relative content of fibrin, DNA and VWF in thrombi and analyzed their interrelations and quantitative associations with systemic biomarkers of inflammation and clinical characteristics of the patients. PATIENTS, METHODS: Thrombi extracted from AIS (n = 17), CAD (n = 18) or PAD (n = 19) patients were processed for scanning electron microscopy, (immune)stained for fibrin, VWF and extracellular DNA. Fibrin fiber diameter, cellular components, fibrin/DNA and fibrin/VWF ratios were measured. RESULTS: Patients' age presented as a strong explanatory factor for a linear decline trend of the VWF content relative to fibrin in thrombi from CAD (adjusted-R2 = 0.43) and male AIS (adjusted-R2 = 0.66) patients. In a subgroup of CAD and PAD patients with dyslipidemia and high (above 80%) prevalence of atherothrombosis a significant correlation was observed between the VWF and DNA content in thrombi (adjusted-R2 = 0.40), whereas a 3.7-fold lower linear regression coefficient was seen in AIS patients, in whom the fraction of thrombi of atherosclerotic origin was 57%. Independently of anatomical location, in patients with atherosclerosis the VWF in thrombi correlated with the plasma C-reactive protein levels. CONCLUSIONS: The observed interrelations between thrombus constituents and systemic inflammatory biomarkers suggest an intricate interplay along the VWF/NET/fibrin axis in arterial thrombosis.

Left atrial appendage size is a marker of atrial fibrillation recurrence after radiofrequency catheter ablation in patients with persistent atrial fibrillation.

INTRODUCTION: There are no consistently confirmed predictors of atrial fibrillation (AF) recurrence after catheter ablation. Therefore, we aimed to study whether left atrial appendage volume (LAAV) and function influence the long-term recurrence of AF after catheter ablation, depending on AF type. METHODS: AF patients who underwent point-by-point radiofrequency catheter ablation after cardiac computed tomography (CT) were included in this analysis. LAAV and LAA orifice area were measured by CT. Uni- and multivariable Cox proportional hazard regression models were performed to determine the predictors of AF recurrence. RESULTS: In total, 561 AF patients (61.9 ± 10.2 years, 34.9% females) were included in the study. Recurrence of AF was detected in 40.8% of the cases (34.6% in patients with paroxysmal and 53.5% in those with persistent AF) with a median recurrence-free time of 22.7 (9.3-43.1) months. Patients with persistent AF had significantly higher body surface area-indexed LAV, LAAV, and LAA orifice area and lower LAA flow velocity, than those with paroxysmal AF. After adjustment left ventricular ejection fraction (LVEF) <50% (HR = 2.17; 95% CI = 1.38-3.43; p < .001) and LAAV (HR = 1.06; 95% CI = 1.01-1.12; p = .029) were independently associated with AF recurrence in persistent AF, while no independent predictors could be identified in paroxysmal AF. CONCLUSION: The current study demonstrates that beyond left ventricular systolic dysfunction, LAA enlargement is associated with higher rate of AF recurrence after catheter ablation in persistent AF, but not in patients with paroxysmal AF.

Glucose levels show independent and dose-dependent association with worsening acute pancreatitis outcomes: Post-hoc analysis of a prospective, international cohort of 2250 acute pancreatitis cases.

BACKGROUND: Metabolic risk factors, such as obesity, hypertension, and hyperlipidemia are independent risk factors for the development of various complications in acute pancreatitis (AP). Hypertriglyceridemia dose-dependently elicits pancreatotoxicity and worsens the outcomes of AP. The role of hyperglycemia, as a toxic metabolic factor in the clinical course of AP, has not been examined yet. METHODS: We analyzed a prospective, international cohort of 2250 AP patients, examining associations between (1) glycosylated hemoglobin (HbA1c), (2) on-admission glucose, (3) peak in-hospital glucose and clinically important outcomes (mortality, severity, complications, length of hospitalization (LOH), maximal C-reactive protein (CRP)). We conducted a binary logistic regression accounting for age, gender, etiology, diabetes, and our examined variables. Receiver Operating Characteristic Curve (ROC) was applied to detect the diagnostic accuracy of the three variables. RESULTS: Both on-admission and peak serum glucose are independently associated with AP severity and mortality, accounting for age, gender, known diabetes and AP etiology. They show a dose-dependent association with severity (p < 0.001 in both), mortality (p < 0.001), LOH (p < 0.001), maximal CRP (p < 0.001), systemic (p < 0.001) and local complications (p < 0.001). Patients with peak glucose >7 mmol/l had a 15 times higher odds for severe AP and a five times higher odds for mortality. We found a trend of increasing HbA1c with increasing LOH (p < 0.001), severity and local complications. CONCLUSIONS: On-admission and peak in-hospital glucose are independently and dose-dependently associated with increasing AP severity and mortality. In-hospital laboratory control of glucose and adequate treatment of hyperglycemia are crucial in the management of AP.

The Differential Impact of the Left Atrial Pressure Components on Pulmonary Arterial Compliance-Resistance Relationship in Heart Failure.

BACKGROUND: An increase in the pulmonary capillary wedge pressure (PAWP) has been shown to impact on the inherent relationship between the pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR), thus augmenting the pulsatile relative to the resistive load of the right ventricle. However, the PAWP comprises the integration of both the steady and the pulsatile pressure components. We sought to address the differential impact of the these distinct PAWP components on the PAC-PVR relationship in a cohort of patients with heart failure. METHODS AND RESULTS: The study population consisted of 192 patients with hemodynamic findings diagnostic for heart failure. Off-line analysis was performed using the MATLAB software. The steady and pulsatile PAWP components were calculated as mid-A pressure and mean pressure during the V-wave oscillation, respectively. The PAC and PVR were hyperbolically and inversely associated and the subgroup of patients with PAWP above the median (>18 mm Hg) displayed a significant left and downward shift of the curve fit (P < .001). The shift in the PAC-PVR fit between patients with higher versus low steady PAWP was not significant (P = .43). In contrast, there was a significant downward and leftward shift of the PVR-PAC curve fit for the subgroup with a higher pulsatile PAWP (P < .001). Furthermore, only the pulsatile PAWP was significantly associated with the time-constant of the pulmonary circulation, assessed as the PAC × PVR product (P < .001). CONCLUSIONS: In patients with heart failure, the pulsatile rather than the steady PAWP component stands for the previously documented shift of the PAC-PVR relationship occurring at an elevated PAWP.