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Background: Pulmonary vein isolation (PVI) is the most effective therapy to achieve rhythm control in atrial fibrillation (AF). Peri-procedural imaging is used in many but not all centers. However, the impact of imaging on safety and efficacy of PVI is not clear. The Israeli Catheter Ablation Registry (ICAR) is a great opportunity to explore this issue in real-world practice., Aim: To describe the real-world utilization of peri-procedural imaging technologies in a large cohort of patients undergoing ablation for AF., Methods: A prospective-multicenter cohort of AF patients who underwent PVI during the years 2019-2021. Peri-procedural imaging (CT, ICE, TEE) was utilized based on the center and operator discretion. The study endpoints were peri-procedural complications and AF recurrence at 12 months follow-up among patients with and without peri-procedural imaging., Results: Between January 2019 and December 2021, a total of 921 patients underwent PVI. Peri-procedural imaging (at least 1 modality of CT, TEE, and or ICE) was utilized in 753 (81.8%) and no imaging among 168 (18.2%) patients. Cryoablation was the dominant energy used for PVI in both groups (92.3% of the non-imaging group, and 95.3% among imaging group), while RF was used in the rest of the patients. Fluoroscopy time was not different between the 2 groups; however, procedure duration was longer among the imaging group (90 min) compared to the non-imaging group (74.5 min, p = 0.006). By 12 months, the incidence of AF recurrence and repeated ablation were not different between the groups. Complications and re-hospitalization for cardiocerebrovascular reasons were not different among the 2 groups. Cox regression model demonstrated no association between preprocedural imaging and the risk of AF recurrence after ablation., Conclusion: This real-world multicenter prospective registry study demonstrated that the rate of complications and the rate of recurrence of AF during 1 year follow-up were not different among patients who had PVI either with or without peri-procedural imaging., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Targeted therapy, such as tyrosine kinase inhibitors (TKIs), has been approved to manage various cancer types. However, TKI-induced cardiotoxicity is a limiting factor for their use. This issue has raised the need for investigating potential cardioprotective techniques to be combined with TKIs. Ribosomal S6-kinases (RSKs) are a downstream effector of the mitogen-activated-protein-kinase (MAPK) pathway; specific RSK isoforms, such as RSK1 and RSK2, have been expressed in cancer cells, in which they increase tumour proliferation. Selective targeting of those isoforms would result in tumour suppression. Moreover, activation of RSKs expressed in the heart has resulted in cardiac hypertrophy and arrhythmia; thus, inhibiting RSKs would result in cardio-protection. This review article presents an overview of the usefulness of RSK inhibitors that can be novel agents to be assessed in future research for their effect in reducing cancer proliferation, as well as protecting the heart from cardiotoxicity induced by TKIs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Peyronie's disease (PD) is a two-phase progressive condition characterized by inelastic plaques in the tunica albuginea of the penis, leading to curvature of the penis. Men with PD also suffer from psychological distress, and sexual life and overall quality of life. Although the preferred surgical treatment modality in Peyronie's disease is plaque incision and grafting, there is lack of studies assessing the erectile function and penile vasculature after the treatment., Objectives: We aimed to evaluate the efficiency and safety of plaque incision and tunica vaginalis of testis grafting in PD., Methods: This was a prospective analysis. Erectile dysfunction was assessed via International Index of Erectile Function Questionnaire (IIEF-5). Penile Doppler ultrasound was performed to assess peak systolic velocity (PSV) and end-diastolic velocity (EDV). Postoperative follow-ups were scheduled at 3, 12, and 24 months., Results: Twenty patients (mean age 47.2 ± 10.8 years) were included. The mean preoperative penile curvature was 48 ± 6.6°. The technical success rate was 100% at 3 months and 90% at 24 months. At follow-up visits, mean erect penile length was no different from the baseline. The baseline mean IIEF-5 score was 18.4 ± 2.5. The mean IIEF-5 score was 20.6 ± 2.6 at 24-month visit (p < 0.0001). Mean PSV significantly increased, while EDV significantly reduced after surgery. There were no serious complications related to surgery., Conclusions: We conclude that surgical reconstruction of penile curvature with tunica vaginalis grafting was a safe and effective procedure in PD., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Next-generation sequencing and computational biology have facilitated the implementation of new combinatorial screening approaches to discover novel enzymes of biotechnological interest. In this study, we describe the successful establishment of a multi-omic approach for the identification of thermostable hydrolase-encoding genes by determination of gene expression levels. We applied this combinatorial approach using an anaerobic enrichment culture from an Azorean hot spring sample grown on green coffee beans as recalcitrant substrate. An in-depth analysis of the microbial community resulted in microorganisms capable of metabolizing the selected substrate, such as the genera Caloramator, Dictyoglomus and Thermoanaerobacter as active and abundant microorganisms. To discover glycoside hydrolases, 90,342 annotated genes were screened for specific reaction types. A total number of 106 genes encoding cellulases (EC 3.2.1.4), beta-glucosidases (EC 3.2.1.21) and endo-1,4-beta-mannosidases (EC 3.2.1.78) were selected. Mapping of RNA-Seq reads to the related metagenome led to expression levels for each gene. Amongst those, 14 genes, encoding glycoside hydrolases, showed highest expression values, and were used for further cloning. Four proteins were biochemically characterized and were identified as thermoactive glycoside hydrolases with a broad substrate range. This work demonstrated that a combinatory omic approach is a suitable strategy identifying unique thermoactive enzymes from environmental samples.

New bioactive 13-epi-neoverrucosane diterpenoid, 5β-acetoxy-13-epi-neoverrucosanic acid (1) along with three known secondary metabolites, 13-epi-neoverrucosan-5β-ol (2), chelodane (3) and (E)-β-farnesene (4) were isolated from the MeOH extract of east Malaysia's liverwort Pleurozia subinflata. The chemical structure of new compound was elucidated by the analyses of its spectroscopic data (FTIR, NMR and HR-ESI-MS). These epi-neoverrucosane-type compounds seem to be notable chemosystematic markers for P. subinflata in Borneo. Compound 3 was widespread in marine sponges however this is the first record for 3 to be found in liverwort. These metabolites were tested for their antifungal potentials against selected fungi from the marine environment. Compound 1 exhibited effective antifungal activity against Lagenidium thermophilum.

DGGE analysis combined with a metagenomic approach was used to get insights into heterotrophic anoxic enrichment cultures of four hot springs of Vale das Furnas, Portugal, using the recalcitrant substrate spent coffee ground (SCG). Parallel enrichment cultures were performed using the major components of spent coffee ground, namely arabinogalactan, galactomannan, cellulose, and proteins. DGGE revealed that heterotrophic thermophilic bacteria are highly abundant in the hydrothermal springs and significant differences in community composition depending on the substrate were observed. DNA, isolated from enrichment cultures of different locations that were grown on the same substrate were pooled, and the respective metagenomes were analyzed. Results indicated that cultures grown on recalcitrant substrate SCG consists of a totally different thermophilic community, dominated by Dictyoglomus. Enrichments with galactomannan and arabinogalactan were dominated by Thermodesulfovibrio, while cultures with casein and cellulose were dominated by Thermus. This study indicates the high potential of thermophilic bacteria degrading recalcitrant substrate such as SCG and furthermore how the accessibility to complex polymers shapes the bacterial community.

Purpose: Multisite cardiac resynchronization therapy (MSCRT) with dual-vein left ventricular (LV) pacing has theoretical advantages over conventional CRT in faster and more physiological LV activation. We aimed to define indications, feasibility, safety, acute, and long-term results of MSCRT., Methods: All patients implanted with MSCRT during 2008-2014 in a single center were reviewed and analyzed., Results: Thirty-nine patients (90% CRT-defibrillators, 64 ± 9 years, 85% male, 74% ischemic etiology) were included. Four groups of indications were recognized: (1) significant tricuspid regurgitation (TR) in patients planned for device implantation without right ventricular lead (n = 3). Follow-up (f/u) of 4 ± 3 years showed major symptomatic improvement in all, with stable LV size and function and deferral of valve surgery; (2) severe heart failure with reduced ejection fraction (HFrEF) and refractory ventricular tachycardia (VT) (n = 4). Except for 1 early death for acute renal failure, all others showed no VT episodes and HF improvement (f/u 4.5 ± 0.5 years); (3) severe HFrEF and wide QRS (≥ 150 ms) or failure of biventricular pacing to narrow QRS during implantation (n = 5). One patient had periprocedural mortality. The others had major clinical improvement; (4) severe HF and narrow QRS/RBBB (n = 27). 23/24 patients with available f/u of 3 ± 1.7 years improved clinically and 57% had EF improvement. In 3 patients, LV1 was disabled and one had LV2 dislodgement., Conclusions: MSCRT is feasible, safe, and valuable in selected patients with a need to avoid RV lead during device implantation, refractory VT with no other solution, severe HFrEF with wide QRS or CRT non-responsiveness, and severe HF without LBBB. Randomized controlled studies are required.

Background: Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF); however, a third of patients are non-responders. The development of quadripolar left ventricular (LV) lead was shown, mainly in single manufactures' registry, to improve LV remodeling and overall mortality. However, limited reports exist on the impact of quadripolar LV leads on HF hospitalization rates in real-life cohorts. We evaluated the clinical outcomes associated with quadripolar LV leads in a large nation-wide registry including all patients implanted with a cardiac resynchronization therapy with defibrillator (CRT-D)., Methods: Between July 2010 and October 2016, 2913 consecutive patients were implanted with a CRT-D and all were prospectively enrolled in the Israeli ICD Registry. Quadripolar LV leads were implanted in 973 (33.4%) patients during this period, and their clinical outcomes were compared to CRT-D recipients implanted with a bipolar LV lead. Primary endpoint was HF hospitalization rate., Results: Quadripolar leads were implanted more in patients with non-ischemic cardiomyopathy and for primary prevention indication and less in post-infarction patients and for secondary prevention of sudden death. Longer QRS duration was observed with quadripolar leads (147 ± 23 vs 143 ± 25; p < 0.001). Outcome event rate for 100 patient years revealed no difference in HF hospitalization rates between bipolar and quadripolar LV leads. Quadripolar lead implant led to lower cardiac mortality, with no influence on overall mortality. Multivariate analysis revealed no significant differences in study endpoints between bipolar and quadripolar LV leads., Conclusion: In a large real-life registry, implantation of quadripolar LV leads in patients with CRT-D did not influence HF hospitalization rates.

To obtain new insights into community compositions of hyperthermophilic microorganisms, defined as having optimal growth temperatures of 80 °C and above, sediment and water samples were taken from two shallow marine hydrothermal vents (I and II) with temperatures of 100 °C at Vulcano Island, Italy. A combinatorial approach of denaturant gradient gel electrophoresis (DGGE) and metagenomic sequencing was used for microbial community analyses of the samples. In addition, enrichment cultures, growing anaerobically on selected polysaccharides such as starch and cellulose, were also analyzed by the combinatorial approach. Our results showed a high abundance of hyperthermophilic archaea, especially in sample II, and a comparable diverse archaeal community composition in both samples. In particular, the strains of the hyperthermophilic anaerobic genera Staphylothermus and Thermococcus, and strains of the aerobic hyperthermophilic genus Aeropyrum, were abundant. Regarding the bacterial community, ε-Proteobacteria, especially the genera Sulfurimonas and Sulfurovum, were highly abundant. The microbial diversity of the enrichment cultures changed significantly by showing a high dominance of archaea, particularly the genera Thermococcus and Palaeococcus, depending on the carbon source and the selected temperature.

Background: Ablation of outflow flow ventricular arrhythmia (VA) originating from aortic cusps can be challenging. The aim of this study was to describe our approach for this ablation., Methods: All patients with outflow VA suspected to originate from aortic cusps according to ECG or after failed ablation from right ventricular outflow tract (RVOT) underwent cardiac CT and radiofrequency ablation. CT image of aortic cusps and coronary arteries was integrated into electroanatomic mapping system by point (left main ostium)-based registration. Ablation was performed at the earliest activation site., Results: Ten patients were included in this case cohort. The ablation catheter was easily maneuvered above and below the aortic valve after registration. Two patients who had previous failed ablation of RVOT focus had successful ablation at right coronary cusp (RCC) and at left coronary cusp (LCC). A patient who had previous failed ablations of RVOT and LCC focuses had successful ablation at RCC-LCC junction. A patient who had previous failed ablation at LCC had successful ablation at RCC-LCC junction. Three patients had successful ablation at RCC-LCC junction, and one patient at LCC. One patient had successful ablation at anterior interventricular vein-great cardiac vein junction. One patient had successful ablation at non-coronary cusp. During follow-up (12-30 months), one patient had recurrence of VA controlled by flecainide. The remaining patients were free of VA without medications., Conclusions: Catheter ablation of VA originating from aortic cusps is safe and effective. CT image integration into electroanatomic mapping system can be helpful in this challenging ablation.

Calcified amorphous tumors (CAT) of the heart are rare primary cardiac tumors characterized by heavy myocardial and valve apparatus calcification. The relationship of the entity with ventricular arrhythmia, if any, is unknown. We describe a case of cardiac CAT in a 58-year-old woman with prior cardiac arrest and recurrent ventricular tachycardia who presented for radiofrequency ablation. Pre-ablation intracardiac echocardiogram revealed the characteristic endomyocardial calcific pattern associated with this tumor that precluded catheter manipulation in the left ventricle. The imaging characteristics and management are described.

Catheter ablation of anteroseptal accessory pathways may be difficult because of the neighboring conduction tissue that may be damaged with ablation. We report a case of an accessory pathway localized to the anteroseptal region. A pathway potential found in the noncoronary cusp of the aortic valve was successfully targeted for ablation with cryo energy. Observations during tachycardia and pacing maneuvers suggest that the supravalvar aortic musculature may be an integral component of left anteroseptal pathways that can be safely targeted for cryoablation without injury of the atrioventricular conduction system.