Search Results (16)

Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article

Background/Objectives: Persistent Left Superior Vena Cava (PLSVC) is a condition that may complicate the ablation of Atrioventricular nodal reentry tachycardia (AVNRT). We aimed to report technical experience in ablation under scuh clinical setting. Methods: 3D guided electrophysiological procedure was conducted and PLSVC was confirmed. Slow-pathway ablation for the AVNRT was performed and typical junctional rhythm during the ablation was observed. Results: Exactly the same AVNRT remained inducible after 10 radiofrequency applications, which was very likely because of suboptimal temperature increase due to lacking sustained stability/contact of the catheter given the PLSVC anatomy and the patient’s deep respiration based on our observation during the RF applications. A non-steerable long sheath was introduced to achieve more firm contact of the ablation catheter, the slow-pathway was successfully ablated with just 1 application (seen immediately occurred, continuous typical junctional rhythms during ablation, and significantly better temperature during the ablation). Conclusions: PLSVC-related anatomical changes may destabilize ablation catheter making it difficult to establish sufficient energy delivery at the slow-pathway region and put forward the need for multiple ablations. Timely identifying such scenarios (e.g., insufficient stability, insufficient temperature) could help better plan/change the ablation technique or strategy to achieve better procedure outcomes. This technical report reminds us that typical junctional beats may not be the only determinant for successful ablation of the slow-pathway. The key to the solution often relies on basic ablation biophysics. Full article

The exploration of the cardiac conduction system evolved over a century, marked by groundbreaking discoveries in atrioventricular (AV) nodal physiology. Atrioventricular nodal re-entrant tachycardia (AVNRT), the most prevalent regular tachycardia in humans, remains enigmatic despite extensive research. Detailed examinations of AV nodal anatomy and histology reveal variations in location and shape, influencing electrophysiological properties. Variability in AV nodal extensions and their embryological origins contribute to the complexity of the conduction system. Physiologically, the AV node plays a crucial role in modulating AV conduction, introducing delays for ventricular filling and filtering atrial impulses. Dual-pathway physiology involving fast and slow pathways further complicates AVNRT circuitry. Integrated approaches combining pre-procedural imaging with electroanatomical mapping enhance our understanding of AV nodal structures and high-definition mapping improves precision in identifying ablation targets. Electrophysiological–anatomical correlations may unveil the specific roles of conduction axis components, aiding in the optimization of ablation strategies. This review traces the historical journey from Tawara’s pioneering work to recent integrated approaches aimed at unraveling the intricacies of AV nodal structures while emphasizing the importance of a multidimensional approach, incorporating technological advancements, anatomical understanding, and clinical validation in human mapping studies. Full article

The interpretation of the surface electrocardiogram and intracardiac recordings is key for the appropriate diagnosis and interventional treatment of cardiac arrhythmias. This report describes a patient with both a focal atrial tachycardia (AT) and an atypical atrioventricular-nodal reentrant tachycardia that were repeatedly induced and terminated by atrial ectopic beats. Radiofrequency ablation of the slow pathway, as well as targeted ablation of the specific AT focus effectively eliminated both tachycardias. Full article

Permanent junctional reciprocating tachycardia (PJRT) is a rare form of atrioventricular reentrant tachycardia due to an accessory pathway characterized by slow and decremental retrograde con duction. The arrhythmia typically presents before adulthood with incessant tachycardia leading to cardiomyopathy and heart failure. We report the case of a woman with tachycardia induced cardiomyopathy due to PJRT detected at the age of 54 years. The patient refused to undergo catheter ablation and was successfully treated with a beta blocker. Full article

Background: The aim of this study was to assess long-term efficacy and safety of empirical slow pathway (ESP) ablation in pediatric and adult patients with a special interest in patients without dual AV nodal physiology (DAVNP). Methods: A retrospective single-center review of patients who underwent ESP ablation between December 2014 and September 2022 was performed. Follow-up included telephone communication, letter questionnaire and outpatient presentation. Recurrence was based on typical symptoms. Results: 115 patients aged 6–81 years (median age 36.3 years, 59.1% female; 26 pts < 18 years) were included. A typical history was present in all patients (100%), an ECG documentation of narrow complex tachycardia in 97 patients (84%). Patients were divided into three groups: Group 1 without DAVNP (n = 23), Group 2 with AH jump (n = 30) and Group 3 with AH jump and at least one AV nodal echo beat (n = 62). No permanent AV block was observed. During a median follow-up of 23.6 ± 22.7 months, symptom recurrence occurred in 7/115 patients (6.1%) with no significant difference between the groups (p = 0.73, log-rank test). Symptom recurrence occurred significantly more often in patients without (5/18 patients; 27%) as compared to patients with ECG documentation (2/97 patients; 2.1%; p = 0.025). No correlation between age and success rate was found (p > 0.1). Conclusions: ESP ablation is effective and safe in patients with non-inducible AVNRT. Overall, recurrence of symptoms during long-term follow-up is low, even if no DAVNP is present. Tachycardia documentation before the EP study leads to a significantly lower recurrence rate following ESP ablation. Full article

Radiofrequency (RF) catheter ablation is an effective treatment option for targeting the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT). Previous data suggested that using intracardiac echocardiography (ICE) guidance could improve procedural outcomes when compared to using fluoroscopy alone. In this prospective study, we aimed to compare the effectiveness of an electroanatomical mapping system (EAMS)-guided approach with an ICE-guided approach for SP ablation. Eighty patients undergoing SP ablation for AVNRT were randomly assigned to either the ICE-guided or EAMS-guided group. If the procedural endpoint was not achieved after 8 RF applications; patients were allowed to crossover to the ICE-guided group. The ICE-guided approach reduced the total procedure time (61.0 (56.0; 66.8) min vs. 71.5 (61.0; 80.8) min, p < 0.01). However, the total fluoroscopy time was shorter (0 (0–0) s vs. 83.5 (58.5–133.25) s, p < 0.001) and the radiation dose was lower (0 (0–0) mGy vs. 3.3 (2.0–4.7) mGy, p < 0.001) with EAMS-guidance. The ICE-guided group had a lower number of RF applications (4 (3–5) vs. 5 (3.0–7.8), p = 0.03) and total ablation time (98.5 (66.8–186) s vs. 136.5 (100.5–215.8) s, p = 0.02). Nine out of 40 patients (22.5%) in the EAMS-guided group crossed over to the ICE-guided group, and they were successfully treated with similar RF applications in terms of number, time, and energy compared to the ICE-guided group. There were no recurrences during the follow-up period. In conclusion, the utilization of ICE guidance during SP ablation has demonstrated notable reductions in procedural time and RF delivery when compared to procedures guided by EAMS. In challenging cases, an early switch to ICE-guided ablation may be the optimal choice for achieving successful treatment. Full article

Parathyroid hormone-related peptide (PTHrP) is the primary cause of malignancy-associated hypercalcemia (MAH). We previously showed that PTHrP ablation, in the MMTV-PyMT murine model of breast cancer (BC) progression, can dramatically prolong tumor latency, slow tumor growth, and prevent metastatic spread. However, the signaling mechanisms using lineage tracing have not yet been carefully analyzed. Here, we generated Pthrpflox/flox; Cre+ mT/mG mice (KO) and Pthrpwt/wt; Cre+ mT/mG tumor mice (WT) to examine the signaling pathways under the control of PTHrP from the early to late stages of tumorigenesis. GFP+ mammary epithelial cells were further enriched for subsequent RNA sequencing (RNAseq) analyses. We observed significant upregulation of cell cycle signaling and fatty acid metabolism in PTHrP WT tumors, which are linked to tumor initiation and progression. Next, we observed that the expression levels of a novel lncRNA, GM50337, along with stearoyl-Coenzyme A desaturase 1 (Scd1) are significantly upregulated in PTHrP WT but not in KO tumors. We further validated a potential human orthologue lncRNA, OLMALINC, together with SCD1 that can be regulated via PTHrP in human BC cell lines. In conclusion, these novel findings could be used to develop targeted strategies for the treatment of BC and its metastatic complications. Full article

Background: Determining the mechanism of supraventricular tachycardias with prolongedP ventriculoatrial (VA) intervals is sometimes a challenge. Our objective is to analyse the determinants, time course and diagnostic accuracy (atypical atrioventricular nodal reentrant tachycardias [AVNRT] versus orthodromic reentrant tachycardias through an accessory pathway [ORT]) of spontaneous VA intervals variation in patients with narrow QRS tachycardias and prolonged VA. Methods: A total of 156 induced tachycardias were studied (44 with atypical AVNRT and 112 with ORT). Two sets of 10 measurements were performed for each patient—after tachycardia induction and one minute later. VA and VV intervals were determined. Results: The difference between the longest and the shortest VA interval (Dif-VA) correlates significantly with the diagnosis of atypical AVNRT (C coefficient = 0.95 and 0.85 after induction and at one minute, respectively; p < 0.001). A Dif-VA ≥ 15 ms presents a sensitivity and specificity for atypical AVNRT of 50% and 99%, respectively after induction, and of 27% and 100% one minute later. We found a robust and significant correlation between the fluctuations of VV and VA intervals in atypical AVNRTs (Coefficient Rho: 0.56 and 0.76, after induction and at one minute, respectively; p < 0.001 for both) but not in ORTs. Conclusions: The analysis of VA interval variability after induction and one minute later correctly discriminates atypical AVNRT from ORT in almost all cases. Full article

Aims/Objectives: Patients with bleeding disorders are a rare and complex population in catheter ablation (CA) procedures. The most common types of bleeding disorders are von Willebrand disease (VWD) and hemophilia A (HA). Patients with VWD or HA tend to have a higher risk of bleeding complications compared to other patients. There is a lack of data concerning peri- and postinterventional coagulation treatment. We sought to assess the optimal management of patients with VWD and HA referred for catheter ablation procedures. Methods and Results: In this study, we analyzed patients with VWD or HA undergoing CA procedures at two centers in Germany and Switzerland between 2016 and 2021. Clotting factors were administered in conjunction with hemostaseological recommendations. CA was performed as per the institutional standard. During the procedure, unfractionated heparin (UFH) was given intravenously with respect to the activated clotting time (ACT). Primary endpoints included the feasibility of the procedure, bleeding complications, and thromboembolic events during the procedure. Secondary endpoints included bleeding complications and thromboembolic events up to one year after catheter ablation. A total of seven patients (three VWD Type I, one VWD Type IIa, three HA) underwent 10 catheter ablation procedures (pulmonary vein isolation (PVI): two × radiofrequency (RF), one × laser balloon (LB), one × cryoballoon (CB); PVI + cavotricuspid isthmus (CTI): one × RF; PVI + left atrial appendage isolation (LAAI): one × RF; Premature ventricular contraction (PVC): three × RF; Atrioventricular nodal reentrant tachycardia (AVNRT): one × RF). VWD patients received 2000–3000 IE Wilate i.v. 30 to 45 min prior to ablation. Patients with HA received 2000–3000 IE factor VIII before the procedure. All patients undergoing PVI received UFH (cumulative dose 9000–18,000 IE) with a target ACT of >300 s. All patients after PVI were started on oral anticoagulation (OAC) 12 h after ablation. Two patients received aspirin (acetylsalicylic acid; ASA) for 4 weeks after the ablation of left-sided PVCs. No anticoagulation was prescribed after slow pathway modulation in a case with AVNRT. No bleeding complications or thromboembolic events were reported. During a follow-up of one year, one case of gastrointestinal bleeding occurred following OAC withdrawal after LAA occlusion. Conclusions: After the substitution of clotting factors, catheter ablation in patients with VWD and HA seems to be safe and feasible. Full article

(1) Background: The panoramic view of a novel wide-band dielectric mapping system could show the individual anatomy. We aimed to compare the feasibility, efficacy and safety of the panoramic view guided approach for ablation of AVNRT with the conventional approach. (2) Methods: Ablation distributions in eight patients were retrospectively analyzed using the panoramic view. The para-slow-pathway (para-SP) region was divided into three regions, and the region that most frequently appeared with the appropriate junctional rhythm or eliminated the slow-pathway was defined as the adaptive slow-pathway (aSP) region. Twenty patients with AVNRT were then ablated in the aSP region under the panoramic view and compared with 40 patients using the conventional approach. (3) Results: Thirty ablation points were analyzed. The majority of effective points (95.0%) were located in the inferior and anterior portions of the para-SP region and defined as the aSP region. Baseline characteristics, fluoroscopic duration, and mean number of ablations were similar among the two groups. The panoramic view group had a significantly higher percentage of appropriate junctional rhythm (81.9% ± 26.0% vs. 55.7% ± 30.5%, p = 0.002) than the conventional group. (4) Conclusions: The use of the panoramic view for AVNRT ablation achieved similar clinical endpoints with higher ablation efficiency than the conventional approach. Full article

Catheter ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT) is mainly performed using anatomical landmarks. We sought to see whether a new ablation catheter equipped with mini-electrodes may facilitate the mapping of slow pathway potentials for AVNRT ablation. We prospectively included patients referred for AVNRT in our center. Mapping and ablation were performed using an irrigated catheter equipped with 3 insulated mini-electrodes on the distal tip. Thirteen consecutive patients were included (85% female, median age 46 years). Slow pathway potentials could be identified in 77% of cases on mini-electrode bipolar tracings, versus 15% on conventional bipolar tracings (p = 0.0009). At the end of the procedure, double potentials on the ablation line were identified in all patients, only on mini-electrode bipolar tracings. Following ablation, an interval separating double potentials in sinus rhythm ≥15% of baseline tachycardia cycle length was associated with non-inducibility in all patients (p < 0.0001). No recurrence occurred during 1 year of follow-up. The use of mini-electrodes may help target slow pathway potentials during AVNRT ablation. Identification of sufficiently split double potentials on the ablation line might represent an electrophysiological endpoint in these patients. Full article

HTRA2 is a mitochondrial protein, mutations in which are associated with autosomal dominant late-onset Parkinson’s disease (PD). The mechanisms by which HTRA2 mutations result in PD are poorly understood. HTRA2 is proposed to play a proteolytic role in protein quality control and homeostasis in the mitochondrial intermembrane space. Its loss has been reported to result in accumulation of unfolded and misfolded proteins. However, in at least one case, PD-associated HTRA2 mutation can cause its hyperphosphorylation, possibly resulting in protease hyperactivity. The consequences of overactive mitochondrial HTRA2 are not clear. Dictyostelium discoideum provides a well-established model for studying mitochondrial dysfunction, such as has been implicated in the pathology of PD. We identified a single homologue of human HTRA2 encoded in the Dictyostelium discoideum genome and showed that it is localized to the mitochondria where it plays a cytoprotective role. Knockdown of HTRA2 expression caused defective morphogenesis in the multicellular phases of the Dictyostelium life cycle. In vegetative cells, it did not impair mitochondrial respiration but nonetheless caused slow growth (particularly when the cells were utilizing a bacterial food source), unaccompanied by significant defects in the requisite endocytic pathways. Despite its protective roles, we could not ectopically overexpress wild type HTRA2, suggesting that mitochondrial HTRA2 hyperactivity is lethal. This toxicity was abolished by replacing the essential catalytic serine S300 with alanine to ablate serine protease activity. Overexpression of protease-dead HTRA2 phenocopied the effects of knockdown, suggesting that the mutant protein competitively inhibits interactions between wild type HTRA2 and its binding partners. Our results show that cytopathological dysfunction can be caused either by too little or too much HTRA2 activity in the mitochondria and suggest that either could be a cause of PD. Full article

Radiofrequency ablation of the slow pathway is an effective method of treatment in children with atrioventricular nodal reentrant tachycardia. The aim of our study was to evaluate anterograde conduction properties in children before and after radiofrequency ablation of the slow pathway and to determine the efficacy and safety of this method.
Material and methods. Noninvasive transesophageal electrophysiological examination was performed in 30 patients at the follow-up period (mean duration, 3.24 years) after radiofrequency ablation of the slow pathway.
Results. The slow pathway function was observed in 13 patients one day after ablation, in 26 patients during the follow-up period, and in 28 patients after administration of atropine sulfate. Atrioventricular node conduction was significantly decreased the following day after ablation and at the follow-up versus the preablation (165.2 [30.2] bmp and 146.3 [28.5] bpm versus 190.9 [31.4] bpm; P<0.001). The atrioventricular node effective refractory period prolonged significantly the following day after ablation and at the follow-up versus the preablation (319.3 [55.3] ms and 351.0 [82.1] ms versus 248.3 [36.6] ms; P<0.001). Effective refractory period of the fast pathway prolonged significantly as compared with the preablation (from 408.0 [60.4] ms to 481.2 [132.9] ms; P=0.005). The prolongation of effective refractory period of the slow pathway was more significant than effective refractory period of the fast pathway at the follow-up (P<0.001). Two late recurrences occurred; one patient had atrial tachycardia.
Conclusion. Children with atrioventricular nodal reentrant tachycardia can be effectively and safety cured by ablative therapy. The end-point during slow pathway ablation should be the abolition of tachycardia with preservation of dual atrioventricular nodal physiology. Full article