Efficient Ablation Research Articles

Bi-stability in femtosecond laser ablation by MHz bursts

In this work, a bi-stable behavior of laser ablation efficiency and quality was controlled by fluence and burst length. The plasma shielding of incoming laser radiation caused sudden jumps with a significant decrease in ablation efficiency for every even number of pulses in the burst. The attenuation of incoming laser radiation by plasma created by the previous pulse was incorporated into the toy model of burst ablation efficiency. The mathematical recurrence relation has been derived for the first time, binding ablation efficiency for the next pulse with the efficiency of the previous pulse, which predicts bi-stability, as well as sudden jumps occurring in ablation efficiency depending on the number of pulses in burst with the response to changes of the control parameter of peak laser fluence in the pulse. The modeling results using new recurrence relation showed stable and bi-stable ablation efficiency depending on burst fluence and the number of pulses, which agreed well with experimental data. The extremely efficient laser ablation has been achieved by optimizing the shielding effect using three pulses in the burst.

Evaluation of Dual-Frequency Switching HIFU for Optimizing Superficial Ablation

ObjectiveDual-frequency high-intensity focused ultrasound (HIFU) thermal ablation is an exceptionally promising technique for treating tumors due to its precision and effectiveness. However, there are still a few studies on improving the accuracy and efficiency of HIFU in superficial ablation applications. This study proposes a method utilizing dual frequency switching ultrasound (DFSU) to enhance the efficiency and precision of superficial treatments. MethodsA dual-frequency HIFU transducer operating at 4.5 MHz and 13.7 MHz was designed, and a dual-frequency impedance matching network was designed to optimize electro-acoustic conversion efficiency. Phantom and ex vivo tests were conducted to measure and compare thermal lesion areas and temperature rises caused by single-frequency ultrasound (SFU) and DFSU. ResultsIn both phantom and ex vivo tests, the utilization of DFSU resulted in larger lesion areas compared to SFU. Moreover, DFSU provided improved control and versatility, enabling precise and efficient ablation. ConclusionDFSU exhibits the ability to generate larger ablation areas in superficial tissue compared to SFU, and DFSU allows flexible control over the ablation area and temperature rise rate. The acoustic power deposition of HIFU can be optimized to achieve precise ablation.

Model predictive controller of voltage dosage for safe and effective electrochemical treatment of tumors

Electrochemical treatment is an emerging technology that employs direct current to treat cancerous tumors. A significant limitation of this method is the lack of a standardized protocol for voltage application. Our study addresses this by aiming to develop an optimal treatment strategy through the integration of mathematical modeling, numerical simulations, and controller design. We introduce a mathematical model that merges transport equations with electrode kinetics to represent the electrochemical treatment of tumor tissue accurately. The COMSOL software is then utilized to simulate this model, serving as a basis for controller design. Generalized model predictive control is applied to adjust the pH by manipulating the voltage applied to the electrodes. Additionally, we derive a second-order model to predictively characterize the system's behavior. Our designed controller successfully maintains the pH in the electrode's vicinity at a desired level (pH = 2), showcasing robust performance in counteracting disturbances and uncertainties. Analysis of the system's dynamic response reveals an effective ablation zone for the tumor located 5 mm from the anode. By controlling the hydrogen concentration near the anode (up to 5 mm), we ensure the optimal current dosage for efficient tumor ablation, thus minimizing potential harm to adjacent healthy tissues. Our findings offer critical insights into devising an optimal strategy for electrochemical cancer therapy, suggesting significant enhancements in the treatment's efficacy and safety. This proposed method holds promise for broader clinical adoption, potentially revolutionizing electrochemical treatment modalities for cancer.

Multifunctional polypeptide-based polymersome for chemophotothermal therapy of melanoma in vitro and in vivo

To date, combination therapy using chemo-photothermal therapy (Ch-PTT) has attracted tremendous interest due to its efficient ablation of cancerous cells. Furthermore, there are several advantages to using peptide-based nanocarriers for theranostic nanoplatforms, such as excellent biocompatibility and biodegradability, significant encapsulation efficacy for lipophilic drugs with negligible drug leakage, excellent stability, and excellent enzymatic degradation. In the current study, a multifunctional theranostic system based on polymersome (vesicular nanocarrier of self-assembled amphiphilic polymer) was developed for targeted Ch-PTT and x-ray CT imaging of melanoma cancer. For this purpose, using ring opening polymerization (ROP) of γ-benzyl l-glutamate-N-carboxyanhydride (LG-NCA) lipophilic polypeptide PLG (poly(γ-benzyl-l-glutamate) was synthesized and covalently linked to bifunctional COOH-PEG-NH2. Next, polypeptide-based polymersome nanocarier based on amphiphilc PEG-PLG was fabricated and co-encapsulated with hydrophilic gold nanorod (AuNR) and lipophilic curcumin (CUR) in aqueous core and lipophilic bilayer of polymersome (P-AuNR-CUR), respectively. Then, Sgc8-c aptamer were decorated on the polymersome surface (Apt-P-AuNR-CUR) for targeted delivery, and the size of P-AuNR-CUR and Apt-P-AuNR-CUR were determined using DLS device (174.3 ± 5.95 and 206 ± 52, respectively). NIR (near-infrared)-laser-triggered drug delivery release performance of multifunctional polymersome was demonstrated in both citrate and phosphate buffer saline. According to both in vitro and in vivo studies, NIR-responsive polymersomes possess remarkable therapeutic efficacy for Chemo-PTT in comparison to individual cancer therapy. Furthermore, the diagnostic capability of the designed nanoplatform was confirmed using in vivo CT scan imaging 6 h post-intravenous injection.

Designing a benign prostatic hyperplasia dual-mode cavitation cloud and boiling histotripsy therapy transducer

Benign prostatic hyperplasia (BPH) is a condition that causes an enlarged prostate leading to lower urinary tract symptoms (LUTS), affecting quality of life. Histotripsy is a non-invasive focused ultrasound technique that mechanically disintegrates tissue wherein cavitation cloud (CH) and boiling histotripsy (BH) are the two commonly used therapy modes. Recent studies have shown successful ablation of BPH tissue in vitro by transducers that were designed for a transabdominal approach. However, this approach may not be successful in treating tissue in vivo, as evidenced in some of the clinical studies, due to challenges with the anatomical position of prostate within humans. Therefore, a need exists in treating it transrectally with a transducer that can perform both CH and BH for efficient ablation. Initial design studies were performed to determine the appropriate source parameters and materials needed for fabricating the combinational therapy transducer for in vivo use. A 3 MHz multi-element source with a focal length of 40 mm and gain of 64 was chosen. The equivalent aperture is 48.5 mm with a 10 mm central opening for image guidance. Non-linear simulations show sufficient peak positive and negative pressures can be achieved for performing both regimes. Further details on the fabrication and characterization of the transducer with benchtop results will be presented.

Cancer-cell-specific Self-Reporting Photosensitizer for Precise Identification and Ablation of Cancer Cells.

Cancer-cell-specific fluorescent photosensitizers (PSs) are highly desired molecular tools for cancer ablation with minimal damage to normal cells. However, such PSs that can achieve cancer specification and ablation and a self-reporting manner concurrently are rarely reported and still an extremely challenging task. Herein, we have proposed a feasible strategy and conceived a series of fluorescent PSs based on simple chemical structures for identifying and killing cancer cells as well as monitoring the photodynamic therapy (PDT) process by visualizing the change of subcellular localization. All of the constructed cationic molecules could stain mitochondria in cancer cells, identify cancer cells specifically, and monitor cancer cell viability. Among these, IVP-Br has the strongest ability to produce ROS, which serves as a potent PS for specific recognition and killing of cancer cells. IVP-Br could translocate from mitochondria to the nucleolus during PDT, self-reporting the entire therapeutic process. Mechanism study confirms that IVP-Br with light irradiation causes cancer cell ablation via inducing cell cycle arrest, cell apoptosis, and autophagy. The efficient ablation of tumor through PDT induced by IVP-Br has been confirmed in the 3D tumor spheroid chip. Particularly, IVP-Br could discriminate cancer cells from white blood cells (WBCs), exhibiting great potential to identify circulating tumor cells (CTCs).

Heterostructure nanozymes with sustainable tumor microenvironment regulation and reinforced hyperthermia-responsive catalytic activities for orchestrated osteosarcoma catalytic therapy

Catalytic therapy employing nanozymes has evoked extensive exploration as a promising regimen for cancer theranostics, with specific reactivity in response to tumor microenvironment (TME). However, inherently deficient catalytic efficiency and instability compromise their anticancer efficacy, thus limiting biomedical applications. Herein, we report a novel gold-based heterostructure nanozyme (ATP@IR) with dual enzymes-mimicking activities and illustrious photothermal effect for bone tumor catalytic treatment, aiming at obtaining balanced synergism of catalytic therapy and hyperthermia. With the advantage of its unique tipping-deposition heterostructure structure, ATP@IR nanozymes expedite the electron-hole pair separation and produce massive hot electron, leading to illustrious photothermal effect for tumor hyperthermia treatment. Intriguingly, ATP@IR nanozymes display both intrinsic peroxidase (POD)-mimicking (Km: 39.56 mM) and catalase (CAT)-mimicking activities under weakly acidic TME, which could breakdown endogenous H2O2 into deleterious hydroxyl radicals (·OH) and simultaneously replenish oxygen, realizing efficient tumor ablation and hypoxia alleviation. Meanwhile, elevated oxygen level is leveraged to synergistically produce more reactive oxygen species by reacting with ICG for enhanced photodynamic efficacy. Benefiting from phenomenal thermal conversion efficiency (η = 73.6 %), the dual enzyme-mimicking activities of nanozymes are dramatically improved upon mild hyperthermia when exposure to laser, which actualize hyperthermia-augmented catalytic treatment. Impressively, the potent antitumor efficacy is demonstrated by in vivo xenograft osteosarcoma models without causing lung metastasis. Accordingly, this work provides a reasonable strategy by integrating nanocatalytic treatment, hyperthermia treatment, and TME modulation for efficient treatment of osteosarcoma.

A thiol-triggered croconaine-chromene integration to induce ferroptosis and photothermal synergistic efficient tumor ablation.

Theranostic probes, combining diagnostic and treatment capabilities, have emerged as promising tools in tumor precision medicine. However, existing probes with constant fluorescence and photothermal activity can result in low signal-to-background ratios and phototoxicity. In this study, we introduced CM-Croc, a novel probe comprised of chromene and croconaine, selectively triggered by thiol. CM-Croc exhibited turn-on fluorescence and released croconaine for photothermal therapy. The croconaine moiety possesses high photothermal conversion efficiency up to 55%. Besides, it demonstrated potent activity against various cancer cell lines at low micromolar concentrations, including drug-resistant variants, through enhanced photothermal therapy combined with the ferroptosis effect. What's more, CM-Croc was proved to inhibit the activity of GPX4 to induce ferroptosis. Finally, CM-Croc was demonstrated to be the first croconaine-derived SOP, which targeted tumors and significantly inhibited tumor growth in vivo following intravenous administration with irradiation. This study showed CM-Croc's potential for enhancing tumor precision medicine.

Posterior wall ablation by pulsed-field ablation: procedural safety, efficacy, and findings on redo procedures.

The left atrial posterior wall is a potential ablation target in patients with recurrent atrial fibrillation despite durable pulmonary vein isolation or in patients with roof-dependent atrial tachycardia (AT). Pulsed-field ablation (PFA) offers efficient and safe posterior wall ablation (PWA), but available data are scarce. Consecutive patients undergoing PWA using PFA were included. Posterior wall ablation was performed using a pentaspline PFA catheter and verified by 3D-electroanatomical mapping. Follow-up was performed using 7-day Holter ECGs 3, 6, and 12 months after ablation. Recurrence of any atrial arrhythmia lasting more than 30 s was defined as failure. Lesion durability was assessed during redo procedures. Posterior wall ablation was performed in 215 patients (70% males, median age 70 [IQR 61-75] years, 67% redo procedures) and was successful in all patients (100%) by applying a median of 36 (IQR 32-44) PFA lesions. Severe adverse events were cardiac tamponade and vascular access complication in one patient each (0.9%). Median follow-up was 7.3 (IQR 5.0-11.8) months. One-year arrhythmia-free outcome in Kaplan-Meier analysis was 53%. A redo procedure was performed in 26 patients (12%) after a median of 6.9 (IQR 2.4-11) months and showed durable PWA in 22 patients (85%) with only minor lesion regression. Among four patients with posterior wall reconnection, three (75%) presented with roof-dependent AT. Posterior wall ablation with this pentaspline PFA catheter can be safely and efficiently performed with a high durability observed during redo procedures. The added value of durable PWA for the treatment of atrial fibrillation remains to be evaluated.

Light-activatable and hyperthermia-sensitive "all-in-one" theranostics: NIR-II fluorescence imaging and chemo-photothermal therapy of subcutaneous glioblastoma by temperature-sensitive liposome-containing AIEgens and paclitaxel.

Nowadays, it is still quite difficult to combat glioblastoma, which is one of the most lethal cancers for human beings. Combinatory therapy, which could not only improve therapeutic efficacy and overcome multiple drug resistance but also decrease the threshold therapeutic drug dosage and minimize side effects, would be an appealing candidate for glioblastoma treatment. Herein, we report fluorescence imaging in the second near-infrared window (NIR-II)-guided combinatory photothermal therapy (PTT) and chemotherapy of glioblastoma with a newly formulated nanomedicine termed PATSL. It is composed of temperature-sensitive liposome (TSL) carriers, NIR-II emissive and photothermal aggregation-induced emission (AIE) dyes, and chemotherapeutic paclitaxel (PTX) as well. PATSL shows spherical morphology with diameters of approximately 55 and 85nm by transmission electron microscopy and laser light scattering, respectively, a zeta potential of -14.83 mV, good stability in both size and photoactivity, strong light absorption with a peak of approximately 770nm, and bright emission from 900nm to 1,200nm. After excitation with an 808-nm laser with good spatiotemporal controllability, PATSL emits bright NIR-II fluorescence signals for tumor diagnosis in vivo, exhibits high photothermal conversion efficiency (68.8%), and triggers drug release of PTX under hypothermia, which assists in efficient tumor ablation in vitro and in vivo. This research demonstrates that "all-in-one" theranostics with NIR-II fluorescence imaging-guided combinatory PTT and chemotherapy is an efficient treatment paradigm for improving the prognosis of brain cancers.

Synergistic Phototherapy-Molecular Targeted Therapy Combined with Tumor Exosome Nanoparticles for Oral Squamous Cell Carcinoma Treatment.

Oral squamous cell carcinoma (OSCC) contributes to more than 90% of all oral malignancies, yet the performance of traditional treatments is impeded by limited therapeutic effects and substantial side effects. In this work, we report a combinational treatment strategy based on tumor exosome-based nanoparticles co-formulating a photosensitizer (Indocyanine green) and a tyrosine kinase inhibitor (Gefitinib) (IG@EXOs) for boosting antitumor efficiency against OSCC through synergistic phototherapy-molecular targeted therapy. The IG@EXOs generate distinct photothermal/photodynamic effects through enhanced photothermal conversion efficiency and ROS generation, respectively. In vivo, the IG@EXOs efficiently accumulate in the tumor and penetrate deeply to the center of the tumor due to passive and homologous targeting. The phototherapy effects of IG@EXOs not only directly induce potent cancer cell damage but also promote the release and cytoplasmic translocation of Gefitinib for achieving significant inhibition of cell proliferation and tumor angiogenesis, eventually resulting in efficient tumor ablation and lymphatic metastasis inhibition through the synergistic phototherapy-molecular targeted therapy. We envision that the encouraging performances of IG@EXOs against cancer pave a new avenue for their future application in clinical OSCC treatment.

Bromine Substitution Improves the Photothermal Performance of π-Conjugated Phototheranostic Molecules.

NIR-II fluorescence imaging-guided photothermal therapy (PTT) has been widely investigated due to its great application potential in tumor theranostics. PTT is an effective and non-invasive tumor treatment method that can adapt to tumor hypoxia; nevertheless, simple and effective strategies are still desired to develop new materials with excellent PTT properties to meet clinical requirements. In this work, we developed a bromine-substitution strategy to enhance the PTT of A-D-A'-D-A π-conjugated molecules. The experimental results reveal that bromine substitution can notably enhance the absorptivity (ϵ) and photothermal conversion efficiency (PCE) of the π-conjugated molecules, resulting in the brominated molecules generating two times more heat (ϵ808 nm ×PCE) than their unsubstituted counterpart. We disclose that the enhanced photothermal properties of bromine-substituted π-conjugated molecules are a combined outcome of the heavy-atom effect, enhanced ICT effect, and more intense bromine-mediate intermolecular π-π stacking. Finally, the NIR-II tumor imaging capability and efficient PTT tumor ablation of the brominated π-conjugated materials demonstrate that bromine substitution is a promising strategy for developing future high-performance NIR-II imaging-guided PTT agents.

Boiling Histotripsy Using Dual-Frequency Protocol on Murine Breast Tumor Model and Promotes Immune Activation.

Histotripsy is an ultrasound-guided, noninvasive, nonthermal ablation therapy that can mechanically lyse target tissues. There have been no reports of enhanced histotripsy for large-volume triple-negative breast cancer (TNBC). This study aims to verify the ability of a novel approach of dual-frequency mode combined with two-stage millisecond-length ultrasound pulses (DF-TS) to accelerate the treatment of murine subcutaneous 4T1 tumors and determine immune changes after treatment. A custom-designed 1.1-/2.2-MHz two-element confocal-annular array was used to treat approximately 6-mm tumors under ultrasound guidance and real-time monitoring. Two-stage millisecond-length ultrasound pulses were used to generate approximate cuboid ablation volumes (diagonal 5-6 mm) within each tumor, with a dose of 100 pulses/point. Immune effects were characterized by changes of pro-inflammatory cytokine levels and infiltration levels of immune cells. In all targeted treatment areas, bubble cloud activity was visualized by ultrasound monitoring. The novel protocol resulted in elliptical and controllable sized lesions, reducing the number of scanning points, and was generally well tolerated. After treatment, tumor growth experienced a seven-day stagnation period, the survival period of mice was prolonged, and the levels of pro-inflammatory cytokines and immune cell infiltration increased. This study demonstrates that DF-TS boiling histotripsy (BH) has a noninvasive, efficient, and precise ablation ability for TNBC and potentially enhances immune responses.

A novel activated NIR-II phototheranostic nanoagent and its application to photothermal therapy

Phototheranostic nanoagent with NIR-II fluorescence imaging and photothermal therapy (PTT) may allow high-quality imaging guided efficient ablation of deep-tissue tumors. Non-specific distribution in vivo may lead to poor imaging results and a risk of damage to normal tissues. However, developing an activable NIR-II nanoagent for photothermal therapy is challenging. Herein, a new polarity-sensitive phototheranostic nanoagent (DC@PEG) is developed for combinational tumor-specific NIR-II fluorescence imaging and photothermal therapy. DC@PEG has a maximum emission exceed 1200 nm at 808 nm excitation. In vivo fluorescence imaging indicated the nanoparticles could accurately distinguish normal tissue (high polarity environment) and tumor tissue (low polarity environment). Furthermore, DC@PEG effectively inhibited the growth of 4T1 tumor under 808 nm laser irradiation with a high photothermal conversion efficiency of 48.1 %. This work provides a promising strategy for development of excellent NIR-II nanoagent with good biocompatibility and deep tissue penetration. This novel nanoagent can served as a robust tool for photothermal therapy of deep tumors.

Catheter Ablation of Persistent AF-Where are We Now?

Persistent atrial fibrillation (AF) is a diverse condition that includes various subtypes and underlying causes of arrhythmia. Progress made in catheter ablation technology in recent years has significantly enhanced the durability of ablation. Despite these advances however, the effectiveness of ablation in treating persistent AF is still relatively modest. Studies exploring the mechanisms behind persistent AF have identified substrate-driven focal and re-entrant sources within the atrial body as crucial in sustaining AF among individuals with persistent AF. Furthermore, the widespread adoption of atrial late gadolinium enhancement cardiac magnetic resonance (CMR) imaging and the ongoing refinement of invasive voltage mapping techniques have allowed for detailed assessment of fibrotic remodelling prior to or at the time of procedure. Translation into clinical practice, however, has yielded overall disappointing results. The clinical application of AF mapping in ablation procedures has not shown any substantial advantages beyond the use of pulmonary vein isolation (PVI) alone and adjunct ablation of fibrotic areas has yielded conflicting results in recent randomized trials. The emergence of pulsed field ablation represents a welcome development in the field and several studies have demonstrated an enhanced safety profile and increased procedural efficiency with this non-thermal energy modality. Pulsed field ablation also holds promise for safe and efficient substrate ablation beyond the pulmonary veins, but further trials are needed to assess its impact on longer term success rates. Continued advancements in our comprehension of AF mechanisms, alongside ongoing developments in catheter technology aimed at safe formation of transmural lesions, are essential for achieving better clinical outcomes for patients with persistent AF.

Epigenetic profiles guide improved CRISPR/Cas9-mediated gene knockout in human T cells.

Genetic modification of specific genes is emerging as a useful tool to enhance the functions of antitumor T cells in adoptive immunotherapy. Current advances in CRISPR/Cas9 technology enable gene knockout during in vitro preparation of infused T-cell products through transient transfection of a Cas9-guide RNA (gRNA) ribonucleoprotein complex. However, selecting optimal gRNAs remains a major challenge for efficient gene ablation. Although multiple in silico tools to predict the targeting efficiency have been developed, their performance has not been validated in cultured human T cells. Here, we explored a strategy to select optimal gRNAs using our pooled data on CRISPR/Cas9-mediated gene knockout in human T cells. The currently available prediction tools alone were insufficient to accurately predict the indel percentage in T cells. We used data on the epigenetic profiles of cultured T cells obtained from transposase-accessible chromatin with high-throughput sequencing (ATAC-seq). Combining the epigenetic information with sequence-based prediction tools significantly improved the gene-editing efficiency. We further demonstrate that epigenetically closed regions can be targeted by designing two gRNAs in adjacent regions. Finally, we demonstrate that the gene-editing efficiency of unstimulated T cells can be enhanced through pretreatment with IL-7. These findings enable more efficient gene editing in human T cells.

"Ice and Fire" Supramolecular Cell-Conjugation Drug Delivery Platform for Deep Tumor Ablation and Boosted Antitumor Immunity.

Cancer recurrence and metastasis are two major challenges in the current clinical therapy. In this work, a novel diketopyrrolopyrrole-based photothermal reagent (DCN) with unique J-aggregation-induced redshift is synthesized to achieve efficient tumor thermal ablation under safe power (0.33Wcm-2 ). Meanwhile, S-nitroso-N-acetylpenicillamine (SNAP) is co-loaded with near-infrared-absorbing DCN in amphiphilic polymers to realize heat-induced massive release of nitric oxide (NO), which can form oxidant peroxynitrite (ONOO- ) to active matrix metalloproteinases (MMPs), thereby degrading the compact tumor extracellular matrix to improve the ablation depth and infiltration of immune cells. Through a facile supramolecular assembly method, the DCN/SNAP nanoparticles are anchored to liquid-nitrogen-frozen cancer cells, achieving enhanced antitumor immune responses and effective inhibition of distant tumors and pulmonary metastases after only one treatment. The safety and effectiveness of this supramolecular cell-conjugation platform are verified by 2D/3D cellular experiments and bilateral tumor model, confirming the thermal-ablation-gas-permeation-antigen-presentation therapeutic mode has promising anticancer prospects.

Synergistic Enzyme‐Mimetic Catalysis‐Based Non‐Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation (Small 42/2023)

Synergistic Enzyme‐Mimetic Catalysis‐Based Non‐Thermal Sonocavitation and Sonodynamic Therapy for Efficient Hypoxia Relief and Cancer Ablation (Small 42/2023)

Effect of dual-optical pulses with temporal energy distribution on laser ablation performance in in vivo zebrafish model.

A Q-switched laser system has been used in a single-pulse mode for skin melasma treatments because of instant heat deposition in the target. Despite the efficient ablation of the melanophores in the skin, the single, high-fluence pulse often causes undesirable damage to the surrounding tissue, leading to high recurrence rates. This study aims to investigate the feasibility of dual-optical pulses with a temporal energy distribution on the melasma treatment in in vivo zebrafish models in comparison to that of the single optical pulse. Based on the optical detection, the dual-optical pulses had a temporal energy distribution ratio of 4:1 and an interval of 61 μs between the two consecutive pulses. According to the histological analysis, the dual pulses removed melanophores and induced a few apoptotic nuclei with minimal recurrence. This study demonstrated that the feasibility of dual-optical pulses (energy ratio = 4:1) could enhance the laser ablation performance in vivo.

Unidirectional conduction characterizing epicardial connections in patients with atrial tachyarrhythmias.

Electrophysiological characteristics of epicardial connections (ECs) in atria and pulmonary veins (PVs) are unclear despite their important contributions to atrial fibrillation (AF). Unidirectional conduction associated with source-sink mismatch can occur in ECs due to their fine fibers with abrupt changes in orientation. We detailed the prevalence and electrophysiological characteristics of unidirectional conduction in the atria and investigated its association with the clinical manifestation of AF. This study retrospectively reviewed electrophysiological studies and radiofrequency catheter ablation in 261 consecutive patients with AF. Unidirectional conduction was observed during ablation encircling the PVs in eight (3.1%) patients, and all occurred in the suspected (N = 4) or definitively (N = 4) recognized ECs. These ECs included three intercaval bundles, four septopulmonary bundles, and one Marshall bundle, and were first manifested in a second procedure in 6 (75%) patients. The unidirectional property was from PV to atrium (exit conduction) in all intercaval bundles and three septopulmonary bundles, and from atrium to PV (entrance conduction) in the remaining two bundles. Intercaval bundles acted as a limb of bi-atrial macro-reentrant tachycardia (50%, three of the six including previous cases). Ablation of the exit outside the PVs, including the right atrium, eliminated ECs in three (38%) patients. All patients remain free from arrhythmia recurrence after a mean 13-month follow-up. A unidirectional conduction property was closely associated with the EC, as estimated by histological findings. Recognition of this fact by electrophysiologists may help to clarify mechanisms for AF and atrial tachycardia and guide the creation of efficient and safe ablation lesion sets.