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Journal articleRisum N, Philbert BT, Svendsen JH, et al., 2026,
Direct His/LBB pacing as an alternative to biventricular pacing in patients with HFrEF and a typical LBBB: Design and rationale for the His-Alternative II trial.
, Am Heart J, Vol: 300BACKGROUND: Cardiac resynchronization therapy (CRT) using biventricular pacing (BiV-CRT) is an established treatment for patients with symptomatic heart failure, reduced left ventricular ejection fraction, and left bundle branch block (LBBB), leading to improvements in symptoms, ventricular function, exercise capacity and survival. Despite these benefits, up to one third of patients fail to respond optimally with no clinical improvement despite meeting current criteria for implantation. Conduction system pacing (CSP), delivered via His bundle pacing or left bundle branch area pacing, has emerged as an appealing alternative by directly engaging the native His-Purkinje system. However, randomized data directly comparing CSP-based CRT with conventional BiV-CRT remain limited. STUDY DESIGN: His-Alternative II is an investigator-initiated, multicenter, randomized non-inferiority trial designed to evaluate whether CRT delivered via CSP is non-inferior to conventional biventricular pacing with respect to left ventricular reverse remodeling. The study enrolls patients with symptomatic heart failure (New York Heart Association class II to III), left ventricular ejection fraction ≤35%, strict LBBB by electrocardiographic criteria, and optimal medical therapy. A total of 150 patients were randomized with a 1:2 randomization ratio to receive BiV-CRT or CSP-based CRT (His bundle pacing or left bundle branch pacing) and followed for 6 months. The primary endpoint is change in left ventricular end-systolic volume assessed by echocardiography; a surrogate endpoint consistently associated with long-term outcomes in CRT populations. Secondary endpoints include functional capacity, symptomatic status, quality of life, electrical resynchronization, and device-related complications. CONCLUSIONS: His-Alternative II is designed to determine whether CSP-based CRT can achieve left ventricular reverse remodeling comparable to that obtained with conventional BiV-CRT. The study will provide
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Journal articleHunt SE, Lemos D, Pericherla SR, et al., 2026,
Gene2Phenotype: A Database of Structured Human Monogenic Diseases and Pathomechanisms.
, J Mol Biol, Vol: 438To facilitate both disease research and personalised medicine, there is an urgent need for accessible, structured data models describing the molecular basis of genetically determined disease. Gene2Phenotype is a database of expert-curated monogenic gene-disease associations, which was established in 2012 to enable efficient prioritisation of likely diagnostic genomic variants. Initially focused on developmental disorders, it has since been extended to support cardiac, eye, skeletal and skin disorders and germline cancer predisposition. We have redesigned and extended Gene2Phenotype, which now openly shares standardised, structured models of rare monogenic diseases, detailing genotype, molecular mechanism and associated phenotypes, curated from scientific literature. The updated platform, which includes a new API, enabling programmatic access, improves the findability, accessibility, interoperability and reusability of detailed rare monogenic disease association data. These data have the potential to accelerate disease research, clinical diagnosis, treatment selection and the development of novel therapies. Gene2Phenotype is available at https://www.ebi.ac.uk/gene2phenotype/.
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Journal articleLuo Y, Ferreira PF, Wen K, et al., 2026,
Optimized Reduced Field of View and Fat Suppression Methods for Interleaved Multislice In Vivo Cardiac Diffusion Tensor Imaging.
, Magn Reson Med, Vol: 96, Pages: 1097-1110PURPOSE: Slice interleaving, a limited phase encode (PE) field of view (FOV), and effective fat suppression are vital for efficient cardiac diffusion tensor imaging (cDTI) with minimal artifacts. This study aimed to optimize reduced FOV and fat suppression methods for interleaved multislice cDTI to improve signal-to-noise ratio (SNR) and minimize artifacts. METHODS: Two-slice motion compensated spin echo datasets from 20 healthy volunteers were acquired. Four reduced PE FOV sequences were evaluated: 2DRF pulse; applying either 180 ° or 90 ° pulses in PE direction; and the proposed flip-back sequence with a nonselective 180 ° pulse after readout to restore inverted magnetization. Four fat suppression techniques were implemented: no fat suppression (standard); fat saturation; binomial water excitation and spectral attenuated inversion recovery (SPAIR). RESULTS: The proposed flip-back sequence with SPAIR achieved the highest median SNR, and its SNR values are significantly higher ( p < 0.01 ) than 2DRF with SPAIR as current state-of-the-art. SPAIR and water excitation demonstrated comparable performance when combined with the flip-back sequence, and both yielded superior image quality than with no suppression or fat saturation. SPAIR showed robust fat suppression across most subjects, whilst water excitation exhibited advantages in some subjects with a high body mass index. CONCLUSION: The proposed flip-back sequence with SPAIR enables efficient interleaved multislice imaging with reduced PE FOV and effective fat suppression, facilitating clinical translation of in vivo cDTI.
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Journal articleBoichenko V, Frolova S, Voellenkle C, et al., 2026,
Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.
, Biomed Pharmacother, Vol: 201Liver and cardiac fibrosis are critical drivers of chronic organ dysfunction, characterised by fibroblast activation, excessive extracellular matrix deposition, and inflammation. While these fibrotic processes are initiated by distinct triggers and monitored by organ-specific biomarkers, emerging evidence reveals both shared and unique regulatory networks, particularly involving non-coding RNAs (ncRNAs). This review focuses on the roles of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), such as miR-21, miR-22, miR-29, miR-34a, miR-122, miR-133a, miR-210, miR-214, H19, MALAT1, MEG3, NEAT1, and circHIPK3, in modulating key fibrotic pathways including TGF-β/SMAD signalling, oxidative stress, and extracellular matrix remodelling in both hepatic and cardiac tissues. Some ncRNAs exhibit convergent regulatory functions across both organs, while others demonstrate divergent or context-dependent effects within and between tissues. Furthermore, circulating ncRNAs, potentially transferred via extracellular vesicles (EVs), hold potential as minimally invasive biomarkers for early detection of combined cardio-hepatic fibrosis, as exemplified in conditions like Fontan circulation, though extensive validation in large, prospective cohorts is essential. This article summarises established clinical biomarkers, discusses the ncRNA-mediated mechanisms operating in liver and heart fibrosis, distinguishing shared, divergent, and mixed evidence, and explores their translational potential in diagnostics and experimental therapeutics. Finally, it addresses remaining challenges and outlines future directions, emphasising multi-omic integration, longitudinal ncRNA profiling, and mechanistic validation to advance precision management of fibrotic diseases.
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Journal articleGonzález CR, Huang B, Yan S, et al., 2026,
Benchmarking Image-Based Motion-Correction Methods for Ultrasound Localization Microscopy.
, Ultrasound Med Biol, Vol: 52, Pages: 1544-1558BACKGROUND: Ultrasound localization microscopy (ULM) achieves sub-diffraction resolution imaging in vivo through localizing and tracking microbubbles. However, the need to accumulate microbubble signals over time makes ULM highly sensitive to tissue motion, necessitating accurate motion correction. The accuracy of motion-correction techniques poses a limit to the attainable resolution, and there is currently no gold standard algorithm or approach. METHODS: This study benchmarked seven publicly available implementations of non-rigid image registration algorithms using two simulated datasets illustrating soft tissue and cardiac images, as well as in vivo acquisitions of a rabbit kidney and human breast tumor. Five benchmarks were used to evaluate the seven implementations using image-based similarity metrics, errors against ground truth deformation fields, robustness to hyperparameter choice and image quality, including data with varying contrast-to-noise ratios. Using Bayesian optimization and Sobol sensitivity analysis, optimal parameters for each algorithm were identified, with guidelines for data-adaptive algorithm selection proposed. RESULTS: Parameter sensitivity analysis was reported for all implementations, which can be used to prioritize parameters when performing optimization. Motion characteristics and image spatial heterogeneity were found to be important factors for implementation accuracy. Spline-based algorithms, such as free-form deformations implemented in Elastix, performed optimally with small deformations and low spatial heterogeneity. In contrast, methods designed for large deformations, such as large deformation metric matching, implemented by Ceritoglu et al., or free-form deformations with diffeomorphic constraints, such as Niftyreg, were effective at correcting larger data displacements with high heterogeneity, but struggled to identify accurate correspondences when deformation magnitudes were small. Invertibility was beneficial when correctin
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Journal articlePalermi S, Zeidaabadi B, Vecchiato M, et al., 2026,
Development and external validation of AI-ECG models in athlete pre-participation screening: Performance, limitations, and clinical implications.
, Int J CardiolBACKGROUND: Pre-participation screening (PPS) in competitive athletes aims to identify cardiovascular diseases associated with sudden cardiac death (SCD). Although the 12‑lead electrocardiogram (ECG) represents the cornerstone of PPS, structural abnormalities may demonstrate limited or incomplete electrical expression, particularly in asymptomatic athletes with physiological remodeling. Artificial intelligence (AI)-enabled ECG models have shown promising performance in hospital-based populations, but their transportability to low-prevalence athlete screening environments remains uncertain. OBJECTIVES: To develop and externally validate a deep learning (DL)-based AI-ECG ensemble model for detecting imaging-confirmed structural heart disease in competitive athletes undergoing PPS. METHODS: A convolutional neural network (CNN) ensemble was trained using hospital-derived ECG images from Beth Israel Deaconess Medical Center (BIDMC, Boston, USA) and externally validated in the Italian Team for Athlete CARDiac evaluation and AI-based Risk prediction (ITACARD-AI) registry. Separate CNNs were developed for valvular heart disease (VHD) and cardiomyopathies (CM) and combined using XGBoost meta-learning. Model performance was assessed using area under the receiver operating characteristic curve (AUROC), subgroup analyses, and threshold-based evaluation. RESULTS: The ITACARD-AI cohort included 1115 competitive athletes (mean age 26 ± 13 years; 70% male), including 48 athletes (4.3%) with VHD and 30 (2.7%) with CM. External validation demonstrated substantial performance degradation compared with hospital-based internal validation. AUROC values decreased to 0.70 (95% CI 0.64-0.75) for VHD and 0.69 (95% CI 0.60-0.78) for CM, indicating only modest discrimination in the screening population. Threshold analyses showed high negative predictive values (~99%) but persistently low positive predictive values (≤8%), reflecting limited disease enrichment and strong prevalence dep
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Journal articleNikolaev VO, Gorelik J, 2026,
Cardiomyocyte T-tubule loss in heart failure - NFκB as a central signalling hub.
, Cardiovasc Res -
Journal articleMazzola M, Wang H, Lang D, et al., 2026,
Loss of caveolar A1 adenosine receptor signalling blunts anti-adrenergic control in heart failure.
, Cardiovasc Res, Vol: 122, Pages: 1329-1343AIMS: Adenosine, acting through A1 adenosine receptors (A1ARs), exerts anti-adrenergic effects by inhibiting β1-adrenergic receptor (β1AR)-mediated cyclic adenosine monophosphate (cAMP) production and contractility in the heart. While the functional interaction between A1ARs and β1ARs is well established in both atrial and ventricular myocytes, the subcellular compartmentalization of this crosstalk and how it is disrupted in heart failure (HF) remains incompletely understood. This study investigates the spatial confinement of A1AR-β1AR signalling within atrial microdomains and assesses how structural remodelling in HF alters this regulatory axis. METHODS AND RESULTS: Quantitative polymerase chain reaction (qPCR) analysis revealed that A1AR is the predominant adenosine receptor subtype in both rat and human atrial tissues. In healthy rat and mouse atrial myocytes, A1AR activation reduced β1AR-induced cAMP production and sarcomere shortening, with suppression of cAMP signals at sarcolemmal microdomains enriched in protein kinase A Type II. This was further supported by scanning ion conductance microscopy-guided scanning patch-clamp, which showed that A1AR suppressed β1AR-driven L-type Ca2+ channel activity at both T-tubule and crest membrane domains. In atrial myocytes isolated from failing rat and human hearts, A1AR-mediated inhibition of β1AR-induced cAMP production and contractility was impaired. Caveolar disruption by methyl-β-cyclodextrin in rat atrial myocytes or via cardiac-specific caveolin-3 (Cav3) knockout in mice abolished this A1AR-mediated inhibition. Notably, cholesterol repletion alone did not restore membrane cAMP regulation, whereas Cav3 overexpression rescued A1AR-dependent suppression, supporting a requirement for Cav3-dependent organization. In mouse atrial preparations isolated from failing hearts, high-resolution optical mapping showed that A1AR-mediated anti-adrenergic regulation of Ca2+ cycling was select
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Journal articleHua Z, Patlatzoglou K, Kappadan V, et al., 2026,
AI-enabled motion artefact correction to replace emission- and excitation-ratiometry in cardiac optical mapping: a proof-of-concept study.
, Cardiovasc Res, Vol: 122, Pages: 1283-1286 -
Journal articleTonko JB, Okafor J, Qureshi N, 2026,
Myocardial Edema After Pulsed Field Ablation: Underrecognized Tissue Effects with Implications for concomitant LAA occlusion.
, Heart Rhythm -
Journal articlePerotto M, Radesich C, Paldino A, et al., 2026,
Variant Site-Specific Natural History of Titin-Induced Cardiomyopathy: An International Multicenter Registry.
, Circ Genom Precis MedBACKGROUND: Titin truncating variants (TTNtv) represent the most common genotype underlying dilated cardiomyopathy but are also detected in the general population, exhibiting incomplete penetrance and marked phenotypic variability. This heterogeneity complicates clinical interpretation and risk stratification. Emerging molecular evidence suggests that truncating location within the gene may influence disease mechanisms. We aimed to investigate whether TTNtv location also affects clinical phenotype and prognosis. METHODS: We established an international multicenter registry of phenotypically affected carriers of pathogenic or likely pathogenic TTNtv. Patients were classified into 3 groups: A-band, Z/I-band, and M-band. A case-control study assessed the enrichment of TTNtv across regions. The primary outcome was a composite of all-cause mortality and heart transplantation. Secondary outcomes included: (1) sudden cardiac death or major ventricular arrhythmias and (2) heart failure-related death/heart transplantation/left ventricular assist device implantation. RESULTS: The study included 467 patients (81% probands, 73% male, median age 47 years, 81% dilated cardiomyopathy phenotype). Most carried TTNtv in the A-band (80% versus 15% Z/I-band and 5% M-band). All groups showed enrichment compared with GnomAD, with greater Bayesian-estimated penetrance for A-band variants. Over a median follow-up of 83 months, the primary end point was similar across groups. However, the risk of sudden cardiac death/major ventricular arrhythmias was significantly higher in M-band carriers (45% M-band versus 23% Z/I-band versus 12% A-band; P=0.001), especially as the first disease manifestation. Band location independently predicted sudden cardiac death/major ventricular arrhythmias risk, whereas left ventricular ejection fraction was predictive only in A- and Z/I-band groups. CONCLUSIONS: TTNtv are differently enriched across the gene in patients with dilated cardiomyopathy/nondilated left
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Journal articleBlackman J, Quon S, Francis DP, et al., 2026,
Association Between Interventional Cardiologist Practice Characteristics, Coronary Artery Bypass Grafting Use, and Clinical Outcomes.
, Eur J Cardiothorac Surg, Vol: 68OBJECTIVES: Quantify inter-operator variation in referred coronary artery bypass grafting (CABG) following angiography and evaluate associations with practice patterns and long-term outcomes. METHODS: Observational study using administrative health data in British Columbia, Canada (2010-2024). Interventional cardiologist-level CABG Rate was defined as the proportion of referred CABGs to total angiograms performed. Variation across Interventionalists was correlated with other practice characteristics. Among patients undergoing angiography followed by revascularization, associations between operator CABG Rate and all-cause mortality, major adverse cardiovascular events (MACEs), and repeat revascularization were evaluated using hierarchical Cox regression. RESULTS: Among 252 408 angiograms by 40 Interventionalists, CABG Rate varied 13-fold (2.03%-26.4%) and was not explained by hospital-level factors alone (intraclass correlation coefficient [ICC]: 0.358; 95% confidence interval [CI], 0.054-0.621). Higher CABG Rates were associated with lower percutaneous coronary intervention (PCI) utilization (R = -0.60; P < .001), lower PCI extensiveness (R = -0.52; P < .001), and lower procedural volume (R = -0.36; P = .022). In 73,603 first-time revascularized patients, CABG Rate was associated with reduced repeat revascularization (hazard ratio [HR] = 0.075; P < .001), without differences in mortality or MACE. CONCLUSIONS: Referred CABG varies markedly between Interventionalists and reflects operator practice style. Higher CABG utilization is associated with more durable revascularization without impact on survival or MACE. Broader implementation of multidisciplinary Heart Teams may improve consistency of care.
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Journal articleKhan S, Sajjad U, Fawaz S, et al., 2026,
Randomized, Placebo-Controlled Trial of Chronic Total Occlusion Percutaneous Coronary Intervention in Stable Angina: The ORBITA-CTO Trial.
, J Am Coll Cardiol, Vol: 88, Pages: 4-18BACKGROUND: Percutaneous coronary intervention for coronary chronic total occlusion (CTO PCI) is offered for symptom and quality of life improvement, despite the absence of blinded randomized evidence. OBJECTIVES: The aim of this study was to assess the efficacy of CTO PCI in the first randomized, placebo-controlled trial of CTO PCI. METHODS: ORBITA-CTO is a multicenter, randomized, blinded trial comparing CTO PCI with a placebo procedure. Patients had angina attributable to a single-vessel CTO, without bystander coronary disease. Angina symptoms were recorded daily using the ORBITA app. After dual-injection coronary angiography, patients were randomized to either CTO PCI or placebo. Blinding was maintained using auditory isolation and deep conscious sedation. Antianginal medications were stopped at randomization and reintroduced on a patient-initiated protocol. At the 6-month follow-up, assessments were repeated. The primary efficacy outcome was the angina symptom score, an ordinal scale combining the daily symptom burden assessed by the ORBITA app, antianginal use, and over-ride events. Secondary outcomes were symptom and quality of life questionnaires and blinding fidelity. RESULTS: Between October 19, 2021 and October 21, 2025, 50 patients were randomly assigned to CTO PCI (n = 25) or placebo (n = 25). One patient randomized to PCI was withdrawn during the procedure because of a complication. All 50 patients were included in the primary analysis. Compared with placebo, CTO PCI resulted in an immediate and sustained improvement in the angina symptom score (OR: 4.38; 95% credible interval [CrI]: 1.57-12.69; probability of benefit [Pr{Benefit}] = 0.996), arising from a clear reduction in the number of episodes of angina (OR: 4.38; 95% CrI: 1.55-11.78; Pr[Benefit] = 0.997). This resulted in an additional 30.6 days free of angina (95% CrI: 11.1-50.7; Pr[Benefit] >0.999). Improvements were also observed with the Seattle Angina Questionnaire in angina frequency (+10
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Journal articleChiew K, Foley MJ, Chotai S, et al., 2026,
Focal and Diffuse Coronary Artery Disease Patterns and Placebo-Controlled Angina Relief With Percutaneous Coronary Intervention: ORBITA-2.
, J Am Coll Cardiol, Vol: 88, Pages: 42-58BACKGROUND: Unblinded studies have demonstrated superior procedural and clinical outcomes of percutaneous coronary intervention (PCI) in focal compared with diffuse coronary artery disease. However, data from the first placebo-controlled study did not demonstrate a differential impact of disease pattern on symptom endpoints. OBJECTIVES: The study sought to test the ability of pattern of coronary artery disease to predict the placebo-controlled efficacy of PCI. METHOD: In the ORBITA-2 (Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina-2) randomized placebo-controlled trial of angioplasty for stable angina, patients underwent prerandomization nonhyperemic pressure wire pullback assessments. Seven blinded interventional cardiologists independently reviewed each pullback trace to categorize disease patterns as focal, diffuse, or mixed. These were assigned numerical values of 1, 0, and 0.5, respectively. Overall disease pattern score was determined by the mean. A score >0.5 was considered focal and ≤0.5 was considered diffuse. Bayesian proportional odds modeling was used. RESULTS: A total of 245 patients with 300 target vessel pullbacks were analyzed. With adjustment for prerandomization nonhyperemic pressure ratio, PCI in focal compared with diffuse disease resulted in greater improvement in angina symptom score (OR: 1.80; 95% credible interval [CrI]: 1.48-2.18; Pr[Benefit] > 99.9%) and daily episodes of angina (OR: 1.55; 95% CrI: 1.26-1.89; Pr[Benefit] > 99.9%). Focal disease also predicted greater placebo-controlled benefit in exercise treadmill time (Pr[Interaction] > 99.9%), Canadian Cardiovascular Society class (Pr[Interaction] = 99.0%), EuroQol Group 5-Dimensions 5-Level questionnaire (Pr[Interaction] = 95.1%), and Seattle Angina Questionnaire angina frequency (Pr[Interaction] = 99.5%). There was weaker evidence of interaction between disease pattern and the placebo-controlled impact of PCI on im
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Journal articleBola H, Arif A, J Hon J, et al., 2026,
Cryoballoon Versus Radiofrequency Ablation for Persistent Atrial Fibrillation: Meta-Analysis of Randomized Trials.
, Pacing Clin ElectrophysiolINTRODUCTION: Pulmonary vein isolation (PVI) alone achieves modest arrhythmia freedom in persistent atrial fibrillation (PeAF). Cryoballoon ablation (CBA) offers a single-shot alternative to radiofrequency ablation (RFA) that streamlines procedural workflow. We aimed to quantify the clinical efficacy, procedural efficiency, and safety of CBA versus RFA through a meta-analysis of randomized controlled trials (RCTs). METHODS AND RESULTS: Systematic review of PubMed, Embase, and Scopus identified 5 RCTs enrolling 1,091 patients (515 CBA, 576 RFA). The primary endpoint was 12-month freedom from any atrial arrhythmia, with isolated AF, and atrial tachycardia/flutter evaluated as secondary endpoints. Random-effects models generated relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CI). Time-to-event data were pooled using a generic inverse-variance approach to derive hazard ratios (HR). CBA and RFA demonstrated equivalent freedom from any arrhythmia (RR 0.97, 95% CI 0.81-1.15; p = 0.71). Time-to-event analysis corroborated a comparable recurrence hazard (HR 0.91, 95% CI 0.67-1.24; p = 0.56; I2 = 0%). Repeat ablation rates were identical (RR 0.93; p = 0.50). CBA significantly reduced procedural time (MD -45.37 min; p < 0.0001), while major complications were comparable (1.5% vs. 2.7%; p = 0.18). Trial sequential analysis indicated that further randomization is unlikely to demonstrate superiority. CONCLUSION: In PeAF, CBA and RFA achieve equivalent 12-month arrhythmia-free survival and comparable repeat-ablation rates, while CBA confers a highly significant reduction in procedural time. However, reliance on 12-month follow-up and heterogeneous rhythm surveillance protocols may limit assessments of true long-term durability.
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Journal articleJones O, Linton N, Bissett S, et al., 2026,
Tau20-RETROmapping System Identifies Driver-Like Activation Patterns in Real-Time During Persistent Atrial Fibrillation.
, Circ Arrhythm ElectrophysiolBACKGROUND: Conventional activation mapping of atrial fibrillation (AF) during clinical procedures is limited by low-amplitude, fractionated electrograms and cycle length variability. The Tau20-RETROmapping stimulator-recorder system (TauRhythm Therapies, United Kingdom) is an investigational device used to identify nonpulmonary vein AF drivers by real-time, high-density activation mapping of uniform wavefronts during AF. We validated the accuracy of the system and applied it to left atrial mapping for evidence of AF drivers. METHODS: Left atrial geometry was acquired using a 3-dimensional electroanatomic mapping system with high-density mapping catheters (CARTO 3 with Optrell, or EnSite X with HD Grid). Electrograms were recorded for 30 seconds at multiple left atrial sites. The Tau20-RETROmapping system generates activation maps of organized wavefronts. System performance was manually validated against randomly sampled local electrograms using a grid sweep of thresholds to identify Pareto-optimal parameters in sinus rhythm, atrial pacing, atrial tachycardia (AT), and AF. The system was then applied to identify putative driver activation patterns during persistent AF. RESULTS: We studied 24 patients undergoing pulmonary vein isolation for AF. Six patients presented in sinus rhythm or AT, in whom the system demonstrated a sensitivity of 100.0% (95% CI, 80.5%-100.0%) and a specificity of 100.0% (85.2%-100.0%). Eighteen patients were mapped in AF: the system had a sensitivity of 94.4% (86.2%-98.4%) and a specificity of 97.1% (89.9%-99.6%) when identifying organized AF wavefronts, and accurately identified the earliest activation in 89.6% (79.7%-95.7%) of waves. Stable propagation originating from the left atrial appendage (LAA) was observed in 3/18 patients, while 8/18 demonstrated competing propagation toward and away from the LAA. Conduction away from the LAA was detected along the anterior (8/18 patients), lateral (8/18 patients), and posterior (7/18 patients) wall
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Journal articleHong W, Zhang Z, Li A, et al., 2026,
A Correlative SICM-OPM Platform for Surface and Volumetric Imaging in Live Cells.
, Adv Sci (Weinh), Vol: 13Live-cell imaging of cell surface topography and intracellular architecture is essential for understanding cellular function. However, conventional approaches often involve trade-offs between resolution, invasiveness, and volumetric coverage. Here, we present an integrated Scanning Ion Conductance Microscope and single-objective Oblique Plane Microscope (SICM-OPM) system that enables simultaneous non-contact topographical imaging and volumetric fluorescence imaging within the same live cell without sample translation. Beyond correlative live imaging, the platform supports nanomechanical mapping with tens-of-nanometers resolution, fluorescence-guided localized molecular delivery via the SICM, and benefits from reduced photobleaching due to light-sheet excitation. We demonstrate this platform's capabilities by visualizing imipramine-induced transverse-tubule (TT) remodeling in live cardiomyocytes, revealing pronounced detubulation of internal TT invaginations while surface TT opening characteristics remain largely preserved, and capturing high-speed correlative volumetric images of clathrin-mediated endocytosis in Cos-7 cells. Additionally, we show precision delivery of fluorescent cargos, including dextrans and α-synuclein, into mammalian cells and diatoms, alongside localized stiffness mapping to evaluate mechanical responses of mammalian cells. We believe this technique opens new avenues for correlative structural, functional, and biophysical studies in live cells, with broad relevance to cell biology, neurodegeneration, and mechanobiology.
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Journal articleKappadan V, Hua Z, Tonko JB, et al., 2026,
Combined emission ratiometry and motion tracking for optical mapping of contracting hearts: Validation with monophasic action potentials.
, J Physiol, Vol: 604, Pages: 5758-5776Cardiac optical mapping in fully contracting hearts is limited by motion artefacts, leading most investigations to rely on excitation-contraction uncoupling despite its impact on physiological relevance. Although motion tracking and ratiometric imaging have each been used to reduce motion artefacts, and their combined use has been demonstrated with excitation ratiometry, systematic validation of emission ratiometry combined with motion tracking against an established electrophysiological reference remains limited. In this study, we integrated emission ratiometry with two-dimensional, marker-free motion tracking to suppress motion-related artefacts during optical mapping of Langendorff-perfused rabbit hearts, leveraging the advantage that emission ratiometry derives both signals from the same excitation pathway and thereby reduces sensitivity to motion-related photometric fluctuations in fluorescence intensity. Motion-corrected optical action potentials were quantitatively validated against simultaneously recorded monophasic action potentials (MAPs), with optical signals extracted from regions adjacent to the MAP electrode. Compared with raw recordings and with either method applied alone, the combined approach produced the closest agreement with MAP-derived repolarization measurements. Bland-Altman analysis indicated no systematic bias at APD70 and APD80, with bias confidence intervals including zero. Cumulative probability analysis revealed a marked improvement in precision following combined motion correction, with the proportion of optical action potential duration (APD) measurements within ±10 ms of MAP increasing from 16.9%, 29.2% and 26.2% in raw recordings to 75.4%, 87.7% and 80% for APD50, APD70 and APD80, respectively. Collectively, these findings establish the integrated motion-correction strategy as a validated framework for accurate quantification of action potentials in contracting hearts, supporting more physiologically relevant optical map
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Journal articleKailey B, Bola H, Wright I, et al., 2026,
Ripple mapping demonstrates putative signals identifying the right inferior nodal extension to the lower nodal bundle during AVNRT.
, Heart Rhythm, Vol: 23, Pages: e1080-e1092BACKGROUND: Mapping wavefronts within the triangle of Koch is challenging owing to multiple small and large amplitude signals within a short time interval. Ripple mapping was designed to overcome these limitations. OBJECTIVE: We tested the feasibility of delineating wavefronts within the triangle of Koch during slow-fast atrioventricular nodal reentrant tachycardia (AVNRT). METHODS: Patients undergoing electrophysiological studies were recruited. Right atrial CARTO maps were collected during atrial pacing, ventricular pacing, and typical AVNRT. Using ripple mapping, we marked His activation during atrial pacing, the earliest retrograde atrial activation during ventricular pacing, the earliest signal during AVNRT (E-AVNRT), and the earliest retrograde right atrial activation during AVNRT. RESULTS: 72 patients were recruited, with typical AVNRT in 40 patients and a full mapping protocol in 30 patients (6327 ± 948 points collected). The E-AVNRT was 14.7 ± 5.3 mm inferior to the earliest His identified during atrial pacing. A wavefront consistent with slow pathway activation started at E-AVNRT taking 22.2 ± 4.8 ms to reach the His cloud with a line of block demarcating the atrial side. This same line formed the ventricular border of atrial activation during atrial pacing, consistent with slow pathway activation over the right inferior nodal extension. These wavefront signals became sharper approaching His but consistently activated a region inferior to the His cloud, consistent with the right inferior nodal extension activating the lower nodal bundle. Earliest retrograde fast pathway-mediated right atrial activation during AVNRT was 57.3 ± 27.1 ms later and 11.7 ± 6.0 mm from E-AVNRT and distinct from the earliest atrial activation during ventricular pacing (7.0 ± 3.2 mm). Successful ablation sites were closer to E-AVNRT than unsuccessful sites (6.4 ± 3.0 vs 14.8 ± 5.6 mm; 95% confidence interval 5.2-7.6 vs 12.2-17
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Journal articleNasilli G, Lin X, Swiatlowska P, et al., 2026,
Decreasing Microtubule Detyrosination Improves Cardiac Mechanics and Sodium Channel Function in Arrhythmogenic Cardiomyopathy.
, Circ Arrhythm Electrophysiol, Vol: 19BACKGROUND: Alterations in microtubule dynamics have been shown to affect cardiomyocyte membrane stiffness and modulate ion channels, including the cardiac sodium channel. While conditions, such as heart failure and Duchenne muscular dystrophy, are associated with increased detyrosination of microtubules and reduced sodium current, a potential role for microtubule detyrosination in arrhythmogenic cardiomyopathy has not been explored. We here investigated the impact of microtubule detyrosination on membrane stiffness, cardiac sodium channel distribution, and function in mouse and human models of arrhythmogenic cardiomyopathy. METHODS: Isolated ventricular cardiomyocytes from mice with cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 (plakophilin-2), as well as PKP2-c.2013delC, and isogenic control human-induced pluripotent stem cell-derived-cardiomyocytes were incubated for 2 to 4 hours with compounds known to decrease microtubule detyrosination (parthenolide, 10 µmol/L; EpoY, 20 µmol/L) or vehicle (dimethyl sulfoxide). Immunocytochemistry, mechano-scanning ion conductance microscopy, patch-clamp analysis, and stochastic optical reconstruction microscopy were performed. RESULTS: Cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 mouse cardiomyocytes displayed increased microtubule detyrosination and membrane stiffness, which were both attenuated by parthenolide treatment. Parthenolide significantly increased whole-cell sodium current density in cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 mouse cardiomyocytes, with macropatch measurements demonstrating that this increase occurred both at the intercalated disc and lateral membrane. Stochastic optical reconstruction microscopy analysis revealed that parthenolide increased cardiac sodium channel cluster density at the intercalated disc of cardiomyocyte-specific, tamoxifen-activated knockout of PKP2 mouse cardiomyocytes. In contrast, parthenolide had no effect on sodium c
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