Functional substrate mapping of atrium in patients with atrial scar: A novel method to predict critical isthmus of atrial tachycardia.

Atrial tachycardia (AT) is a common rhythm disorder, especially in patients with atrial structural abnormalities. Although voltage mapping can provide a general picture of structural alterations which are mainly secondary to prior ablations, surgery or pressure/volume overload, data is scarce regarding the functional characteristics of low voltage regions in the atrium to predict critical isthmus of ATs. Recently, functional substrate mapping (FSM) emerged as a potential tool to evaluate the functionality of structurally altered regions in the atrium to predict critical sites of reentry. Current evidence suggested a clear association between deceleration zones of isochronal late activation mapping (ILAM) during sinus/paced rhythm and critical isthmus of reentry in patients with left AT. Therefore, these areas seem to be potential ablation targets even not detected during AT. Furthermore, abnormal conduction detected by ILAM may also have a role to identify the potential substrate and predict atrial fibrillation outcome after pulmonary vein isolation. Despite these promising findings, the utility of such an approach needs to be evaluated in large-scale comparative studies. In this review, we aimed to share our experience and review the current literature regarding the use of FSM during sinus/paced rhythm in the prediction of re-entrant ATs and discuss future implications and potential use in patients with atrial low-voltage areas.

FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma.

Deletion of CDKN2A occurs in 50% of glioblastomas (GBM), and IFNA locus deletion in 25%. These genes reside closely on chromosome 9. We investigated whether CDKN2A and IFNA were co-deleted within the same heterogeneous tumour and their prognostic implications. We assessed CDKN2A and IFNA14 deletions in 45 glioma samples using an in-house three-colour FISH probe. We examined the correlation between p16INK4a protein expression (via IHC) and CDKN2A deletion along with the impact of these genomic events on patient survival. FISH analyses demonstrated that grades II and III had either wildtype (wt) or amplified CDKN2A/IFNA14, whilst 44% of GBMs harboured homozygous deletions of both genes. Cores with CDKN2A homozygous deletion (n = 11) were negative for p16INK4a. Twenty p16INK4a positive samples lacked CDKN2A deletion with some of cells showing negative p16INK4a. There was heterogeneity in IFNA14/CDKN2A ploidy within each GBM. Survival analyses of primary GBMs suggested a positive association between increased p16INK4a and longer survival; this persisted when considering CDKN2A/IFNA14 status. Furthermore, wt (intact) CDKN2A/IFNA14 were found to be associated with longer survival in recurrent GBMs. Our data suggest that co-deletion of CDKN2A/IFNA14 in GBM negatively correlates with survival and CDKN2A-wt status correlated with longer survival, and with second surgery, itself a marker for improved patient outcomes.

Functional substrate mapping characteristics during sinus rhythm predicts critical isthmus of reentrant atrial tachycardia.

BACKGROUND: Atrial tachycardia (AT) is a commonly encountered rhythm disorder in patients with underlying atrial scar. The role of atrial late activation mapping during sinus rhythm to predict the critical isthmus (CI) of AT has yet to be systematically evaluated. We aimed to investigate the relationship between the functional substrate mapping (FSM) characteristics and the CI of reentrant ATs in patients with underlying atrial low-voltage areas. METHODS: Patients with history of left AT who underwent catheter ablation with 3D mapping using high-density mapping were enrolled. Voltage map and isochronal late activation mapping were created during sinus/paced rhythm to detect deceleration zones (DZ). Electrograms with continuous-fragmented morphology were also tagged. After induction of AT, activation mapping was performed to detect CI of the tachycardia. Atrial tachyarrhythmia (ATa) recurrence was defined as detection of atrial fibrillation or AT (≥30 s) during the follow-up. RESULTS: Among 35 patients [mean age: 62 ± 9, gender: 25 (71.5%) female] with left AT, a total of 42 reentrant ATs induced. Voltage mapping during sinus rhythm revealed low-voltage area of 37.1 ± 23.8% of the left atrium. The mean value of bipolar voltage, EGM duration, and conduction velocity during sinus rhythm corresponding to CI of ATs were 0.18 ± 0.12 mV, 133 ± 47 ms, and 0.12 ± 0.09 m/s, respectively. Total number of DZs per chamber was 1.5 ± 0.6, which were located in the low-voltage zone (<0.5 mV) detected by high-density mapping. All CIs of reentry were colocalized with DZs detected during FSM. The positive predictive value of DZs to detect CI of inducible ATs is 80.4%. Freedom from ATa after the index procedure was 74.3% during a mean follow-up of 12.2 ± 7.5 months. CONCLUSION: Our findings demonstrated the utility of FSM during sinus rhythm to predict the CI of AT. DZs displayed continuous-fragmented signal morphology with slow conduction which may guide to tailor ablation strategy in case of underlying atrial scar.

Percutaneous interventions of coronary artery fistulas: a single-center experience.

Introduction: Coronary artery fistula (CAF) is a congenital communication between the coronary artery and other vascular structures or cardiac chambers. Percutaneous CAF closure is an emerging alternative to surgery, but long-term outcome data are limited. Aim: To review our center's experience with percutaneous CAF closure methods. Material and methods: Patients who were admitted to our department and underwent percutaneous coronary artery fistula intervention between January 2002 and April 2022 due to presence of CAF-related symptoms or complications were retrospectively analyzed. Data were obtained retrospectively from the hospital electronic database. Results: A total of 39 patient were included. Mean age was 57.3 ±12.5 years and 23 (59%) patients were male. The most common symptom was angina (69.2%) and 51.2% of the patients were under treatment with at least one anti-anginal agent at admission. The right coronary artery (n = 19) and left anterior descending artery (n = 19) were the most common sites of CAF origin, and the pulmonary artery (n = 22) was the main drainage site. Coil embolization was performed most frequently and occlusion via cyanoacrylate in 3 patients and detachable balloon angioplasty in 1 patient were preferred. Percutaneous occlusion was achieved in 34 cases, 2 of the 5 failed cases underwent surgical occlusion, and remaining patients were treated with anti-anginal drugs. Complications occurred in 6 (15.3%) patients and all of the patients recovered without sequelae. Conclusions: Coronary artery fistulas may present with different symptoms or complications and there are several techniques for percutaneous occlusion. Percutaneous closure of CAF is feasible and safe in anatomically suitable vessels, with good results at follow-up.

Left Atrial Appendage Occlusion in Patients With Thrombus in Left Atrial Appendage.

BACKGROUND: Atrial appendage (LAA) occlusion is a therapeutic option for thromboembolic prevention in atrial fibrillation (AF) patients who have contraindications to oral anticoagulation (OAC) or high risk of bleeding. Traditionally, thrombus in the LAA has been considered a contraindication for LAA occlusion. Recently, resistant thrombus formation in patients using OACs was suggested as an indication for LAA occlusion. METHODS AND RESULTS: In this single-center study, we evaluated the safety and efficacy of LAA occlusion in patients with a thrombus in the LAA. Twelve non-valvular AF patients who had a thrombus in the LAA were enrolled. The mean age was 71.8 years (range, 62-83 years). Permanent AF was present in all patients. Mean CHA2DS2-VASc score was 4.9 (range, 2-8) and mean HAS-BLED score was 4.8 (range, 3-6). Thrombi in the LAA were classified as type 1 (proximal to mid) and type 2 (distal) in 3 and 9 patients, respectively. Median follow-up duration was 12 months (interquartile range, 6-24 months). LAA occlusion was performed successfully with Amplatzer Amulet device without any significant periprocedural adverse events in all 12 patients. Transesophageal echocardiography (TEE) was performed at 1 and 6 months post procedure. Cardiovascular and all-cause mortality, significant ischemic cerebrovascular events, worsening heart failure, and major bleeding events did not occur during follow-up. Device-related thrombus was not observed with TEE in any patient. CONCLUSION: Our study showed that percutaneous LAA closure could be a therapeutic option for patients with resistant LAA thrombus.

PPP2R3C gene variants cause syndromic 46,XY gonadal dysgenesis and impaired spermatogenesis in humans.

Context Most of the knowledge on the factors involved in human sexual development stems from studies of rare cases with disorders of sex development. Here, we have described a novel 46, XY complete gonadal dysgenesis syndrome caused by homozygous variants in PPP2R3C gene. This gene encodes B″gamma regulatory subunit of the protein phosphatase 2A (PP2A), which is a serine/threonine phosphatase involved in the phospho-regulation processes of most mammalian cell types. PPP2R3C gene is most abundantly expressed in testis in humans, while its function was hitherto unknown. Patients and methods Four girls from four unrelated families with 46, XY complete gonadal dysgenesis were studied using exome or Sanger sequencing of PPP2R3C gene. In total, four patients and their heterozygous parents were investigated for clinical, laboratory, immunohistochemical and molecular characteristics. Results We have identified three different homozygous PPP2R3C variants, c.308T>C (p.L103P), c.578T>C (p.L193S) and c.1049T>C (p.F350S), in four girls with 46, XY complete gonadal dysgenesis. Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities, renal agenesis and neuromotor delay. We have shown a decreased SOX9-Phospho protein expression in the dysgenetic gonads of the patients with homozygous PPP2R3C variants suggesting impaired SOX9 signaling in the pathogenesis of gonadal dysgenesis. Heterozygous males presented with abnormal sperm morphology and impaired fertility. Conclusion Our findings suggest that PPP2R3C protein is involved in the ontogeny of multiple organs, especially critical for testis development and spermatogenesis. PPPR3C provides insight into pathophysiology, as well as emerging as a potential therapeutic target for male infertility.