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Book chapterAbdi A, Jeviskov J, Hussain A, et al., 2027,
Regional Myocardial Strain Estimation with MyoTrackerChrono
, Pages: 131-142Cardiovascular diseases require precise, non-invasive diagnostic tools to assess regional myocardial function. While Speckle Tracking Echocardiography (STE) is widely used to measure myocardial strain, traditional block-matching and optical flow algorithms frequently fail due to acoustic noise and out-of-plane speckle decorrelation. This paper introduces MyoTrackerChrono, a hybrid deep learning architecture designed for robust, sparse point tracking in echocardiography. By integrating a Temporal Adapter between a spatial convolutional encoder and a tracking transformer, the model explicitly aggregates temporal context early in the feature extraction phase. This allows for stable tracking even during rapid cardiac phases or momentary signal loss. Validated on physics-based synthetic benchmarks, MyoTrackerChrono improves pixel-level tracking accuracy (Mean Absolute Error) by 33.0% over baseline models and reduces strain estimation error in mechanically complex mid-wall segments by over 64%. Furthermore, the architecture operates at an effective inference rate of 1382 FPS, confirming its feasibility for rapid post-acquisition clinical deployment.
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Book chapterUfumaka I, Alibakhshi A, Fernandes P, et al., 2027,
Multi-Expert Consensus as a Label-Free Quality Surrogate for Echocardiographic LV Segmentation
, Pages: 235-247Automated left ventricular (LV) segmentation is fundamental to echocardiographic assessment of cardiac function, yet most models report aggregate performance without accounting for variation in image quality. In clinical practice, poor acoustic windows produce ambiguous endocardial boundaries where both automated predictions and expert annotations become unreliable. We propose a label-free quality surrogate, q<inf>dice</inf>, derived from pairwise Dice disagreement across 11 independent clinical experts, requiring no explicit quality labels. Using this surrogate, we conduct a quality-stratified evaluation of three architecturally distinct models (T1, T2, and T3) on the UnityLV-MultiX dataset. T1 is a sparse keypoint model, T2 uses a dense binary mask representation, and T3 is a triple-head hybrid architecture in which predicted keypoint heatmaps guide segmentation feature attention through a differentiable spatial gate. All models are trained on a single-expert dataset and evaluated against a multi-expert consensus using Dice, HD95, MSD, and ejection fraction MAE. A leave-one-out analysis enables direct comparison of model and expert consistency against a common multi-expert reference. All three models exceed every individual expert in overall Dice. T3 achieves the highest Dice across all quality bands (0.937, 0.952, and 0.960 at Q<inf>low</inf>, Q<inf>mid</inf>, and Q<inf>high</inf> respectively; 0.949 overall). It shows the lowest EF MAE overall (5.24%), representing a 38% reduction relative to the expert mean (8.46%). T3’s keypoint and segmentation heads agree far more closely with each other than any cross-model pair (ρ=0.856), yet residual disagreement between the two heads concentrates on low-quality frames, providing a built-in, single-inference reliability flag without any external reference.
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Book chapterAlibakhshi A, Jevsikov J, Ufumaka I, et al., 2027,
Phase-Guided Quality Regression in Apical Echocardiography via CNN-LSTM: A Systematic Backbone Benchmarking Study
, Pages: 17-30Apical view acquisition errors in echocardiography can lead to inaccurate estimation of clinically important measurements, including ventricular volume, ejection fraction, and strain. In this work, we propose a phase-centred CNN-LSTM framework for automated regression of apical image quality in echocardiographic studies, investigating which backbone architecture can most effectively predict a continuous reduction in left ventricular long-axis length without relying on explicit mask-based measurements. A patient-specific reference standard was generated by first identifying end-diastole using a phase detection model and then measuring LV long-axis length. For each patient, the scan with the maximum observed LV length served as the patient-specific reference, and deviations across other scans were quantified using a heuristic formulation based on relative length reduction. Using this systematic labelling strategy, eight CNN-LSTM backbone architectures were trained and compared on 1,799 echocardiographic studies from 100 patients, comprising apical four-chamber and apical two-chamber views, with the goal of directly regressing the degree of length reduction from raw image sequences alone. Across backbone comparisons, convolution-based models showed the strongest overall performance, with EfficientNetV2 achieving the lowest regression error for apical four-chamber views and ConvNeXt-Tiny and ResNet50-level models showing competitive performance in apical two-chamber views. To assess clinical relevance, two expert-annotated evaluation datasets, each labelled by 10 experts, were used for ranking-based comparison against expert consensus. The proposed AI approach demonstrated agreement with expert consensus at a level comparable to several human experts and showed meaningful ability to identify scans associated with overestimation and underestimation of key echocardiographic measurements. These findings support the potential of backbone-driven regression of apical view qua
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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 Cardiol, Vol: 461BACKGROUND: 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 st
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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 articleEl-Medany A, Birdi AR, Abraham A, et al., 2026,
From Wrist to Heart: Clinical Validation and Real-World Translation of Wearable & Portable AI-enhanced ECG
, European Heart Journal - Digital Health<jats:title>Abstract</jats:title> <jats:p>Wearable and portable electrocardiogram devices are shifting cardiovascular monitoring beyond clinician-directed testing, driven by consumer-led self-monitoring, remote care, and preventative cardiology. Artificial intelligence may enhance the value of these devices by supporting automated interpretation, but clinical translation remains uneven. This narrative review synthesises current evidence on artificial intelligence-enhanced electrocardiogram analysis in wearable and portable systems, with emphasis on the gap between technical performance and real-world implementation. Although many advances have been developed using conventional 12-lead electrocardiogram datasets, deployment in wearable and portable devices introduces additional challenges related to device-specific signal acquisition, preprocessing, domain shift, and user-led recording. Evidence is most mature for atrial fibrillation detection, while applications across conduction disease, other arrhythmias, structural phenotypes, and prognostic assessment remain earlier in development and are supported by fewer prospective, device-specific evaluations. Across the field, retrospective and dataset-based studies predominate, with limited evidence that improved detection translates into better patient outcomes or health-system efficiency. Future research should evaluate performance using the intended device, population, and clinical pathway, and determine whether AI-ECG changes management without increasing unnecessary investigation or workload. Establishing clinical value, rather than improving classification accuracy alone, will determine the role of wearable and portable AI-ECG in routine cardiovascular care.</jats:p>
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Journal articleGupta A, Collier D, Steckelmacher J, et al., 2026,
Safety, Acceptability and Efficacy of Noninvasive Transcutaneous-Autonomic Neuromodulation in Uncontrolled Hypertension.
, HypertensionBACKGROUND: Despite antihypertensive medications, ≈40% of patients with hypertension fail to achieve recommended blood pressure (BP) targets. Alternative device-based strategies are often expensive or invasive. We evaluated the safety, acceptability, and potential efficacy of a noninvasive transcutaneous autonomic neuromodulation (tAN) device. METHODS: SCRATCH-HTN (Sham Controlled Randomized Trial Evaluating the Safety, Acceptability and Efficacy of Autonomic Neuromodulation using Transcutaneous Vagal Sensory Stimulation in Uncontrolled Hypertensive Patients) was a double-blind, sham-controlled, phase 2a trial enrolling patients with uncontrolled hypertension (mean daytime systolic BP [SBP] ≥135 mm Hg and diastolic BP ≥85 mm Hg) on 1 or more medications. Participants self-administered active tAN or sham treatment for 30 minutes daily for 14 days, then 10 weekly sessions. Primary end points were safety and acceptability. The primary efficacy end point was change in daytime ambulatory SBP from baseline to 3 months. Secondary end points included BP, heart rate, and quality of life at 1 and 3 months. RESULTS: Sixty-three patients (mean age 47.2 years, 71.4% male, mean daytime BP 150/95 mm Hg) were randomized 2:1 to tAN or sham. tAN did not differ significantly from sham in daytime ambulatory SBP at 3 months (between-group difference, 2.35 mm Hg [95% CI, -4.37 to 9.07]; P=0.49) or 1 month (-1.01 mm Hg [-6.87 to 4.85]; P=0.73). Pre-specified adjusted analysis identified a significant interaction between treatment and baseline SBP (P interaction 0.003): participants with baseline SBP >160 mm Hg showed a greater response to tAN. No significant differences were observed for other secondary end points. tAN was safe and acceptable. CONCLUSIONS: tAN is safe and well-tolerated in patients with hypertension. No significant BP-lowering effect was demonstrated, although a potential benefit in subgroups or a modest effect in a
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Journal articleShun-Shin M, Whinnett Z, 2026,
Cardiac resynchronisation therapy: 30 years of progress.
, Lancet, Vol: 408, Pages: 1150-1151 -
Journal articleArgirò A, Meisner J, Adler E, et al., 2026,
Clinical Characteristics and Outcomes of Hypertrophic Cardiomyopathy Associated With Thin Filament Variants: Insights From the SHaRe Registry.
, Circ Genom Precis MedBACKGROUND: Conflicting evidence exists about whether sarcomeric hypertrophic cardiomyopathy (HCM) caused by genes encoding thin filament proteins (TNNT2, TNNI3, ACTC, TPM1, TNNC1; thin filament HCM) has a distinct clinical presentation and natural history from disease caused by the more commonly involved thick filament genes (MYH7, MYBPC3, MYL2, MYL3; thick filament HCM). METHODS: Retrospective analysis of the Sarcomeric Human Cardiomyopathy Registry. RESULTS: Four hundred eighty-eight patients with thin filament HCM were compared with 3494 patients with thick filament HCM. After controlling for age at diagnosis, sex, and proband status, thin filament HCM was associated with a higher risk of composite ventricular arrhythmias (hazard ratio, 1.48 [95% CI, 1.09-2.01]), cardiac arrest (hazard ratio, 2.02 [95% CI, 1.33-3.06]), and heart transplant or left ventricular assist device implantation (hazard ratio, 2.18 [95% CI, 1.3-3.65]). Younger age at diagnosis was associated with an increased risk for the ventricular arrhythmia composite outcome in thin and thick filament HCM (hazard ratio, 0.93 [95% CI, 0.91-0.94]; hazard ratio, 0.93 [95% CI, 0.93-0.94]; age reported as 5-year increment). Within specific thin filament genes, an increased risk of arrhythmic events or heart transplant/left ventricular assist device implantation was evident for variants in TNNT2 amino acids 92 to 94 (odds ratio versus other TNNT2 variants; odds ratio, 3.02 [95% CI, 1.17-7.49]) and TNNI3 amino acids 191 to 210 (odds ratio versus other TNNI3 variants; odds ratio, 3.5 [95% CI, 1.58-8.02]). CONCLUSIONS: Thin filament HCM seems to carry a higher risk for ventricular arrhythmias and advanced heart failure compared with thick filament HCM. Integrating gene-level and intragene-level information may improve risk stratification in patients with HCM.
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Journal articleIoannou A, Patel R, Mansell J, et al., 2026,
Exploration of Arrhythmia Burden in Cardiac Amyloidosis Using Implantable Loop Recorders: The EXCALIBUR Study.
, J Am Coll Cardiol, Vol: 88, Pages: 1387-1398BACKGROUND: Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy associated with conduction disease and arrhythmias, although their true burden and relationship with disease phenotype remain incompletely defined. OBJECTIVES: The purpose of this study was to prospectively characterize arrhythmic burden using implantable loop recorders and explore associations with amyloid subtype and disease characteristics. METHODS: In this prospective single-center observational study, 110 treatment-naïve patients with a new diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) or light-chain cardiac amyloidosis (AL-CA) underwent comprehensive phenotyping, including cardiac magnetic resonance, followed by implantable loop recorder implantation. RESULTS: Among 110 patients (ATTRwt-CM: 43, ATTRv-CM: 20, AL-CA: 47) bradyarrhythmias with a Class I indication for pacemaker implantation occurred in 17.3% and were more frequent in ATTR-CM than AL-CA (15 [23.8%] vs 4 [8.5%]; P = 0.036). Baseline conduction abnormalities (QRS duration: sHR: 1.03; [95% CI: 1.01-1.04]; P < 0.001) and higher myocardial amyloid burden were associated with subsequent bradyarrhythmic events (ECV: sHR: 1.06 [95% CI: 1.02-1.10]; P = 0.002). New atrial fibrillation occurred in 28.2% of patients without prior atrial fibrillation and was more frequent in ATTR-CM than AL-CA (15 [50.0%] vs 5 [12.2%]; P < 0.001) with higher amyloid burden associated with increased risk (ECV: sHR: 1.04; 95% CI: 1.00-1.08; P = 0.038). During follow-up 21 (19.1%) patients died (ATTR-CM: 10 [15.9%]; AL-CA: 11[23.4%]). In patients with ATTR-CM, the terminal cardiac rhythm was uniformly pulseless electrical activity; in patients with AL-CA, PEA was the terminal rhythm in 9 (81.8%) patients and 2 (18.2%) had sustained ventricular arrhythmias. CONCLUSIONS: In CA, clinically significant arrhythmias are common and frequently asymptomatic. Arrhythmic burden and patterns differ between amyloid subtypes and are close
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Journal articleAdami E, Kim Y, Zheng SL, et al., 2026,
The molecular landscape of hypertrophic cardiomyopathy across disease stages and genotypes.
, Sci Transl Med, Vol: 18Hypertrophic cardiomyopathy (HCM) is marked by asymmetric cardiac wall thickening, hypercontractility, diastolic dysfunction, and fibrosis. Pathogenic sarcomere gene variants cause HCM, but comparable abnormalities occur in patients with unexplained disease, albeit with fewer adverse events. To investigate stage- and genotype-specific disease mechanisms, we performed single-nucleus RNA sequencing of cardiac tissues from 47 patients with HCM, spanning obstructive HCM with preserved systolic function and end-stage HCM, and compared them with nonfailing donor and dilated cardiomyopathy hearts. We identified transcriptional programs associated with cardiomyocyte hypertrophy, fibrosis, and vascular remodeling. Pathogenic variant-positive early-stage HCM samples showed reduced cardiomyocyte abundance and expansion of a proarrhythmogenic cardiomyocyte state. We identified proline-rich 16 (PRR16) as a cardiomyocyte growth-associated gene in HCM and validated its increased expression by RNA in situ hybridization and in a human induced pluripotent stem cell-derived cardiomyocyte HCM model. In HCM samples, fibroblast compositional shifts were associated with profibrotic activation and adverse extracellular matrix remodeling, accompanied by reduced collagen IV (COL4A1/COL4A2) expression and ultrastructural basement membrane abnormalities. HCM samples also exhibited extensive vascular alterations, including shifts in endothelial cell subpopulations, reduced pericyte abundance suggestive of microvascular dysfunction, and increased lymphangiogenic vascular endothelial growth factor C signaling. Unsupervised and supervised machine learning approaches distinguished HCM from dilated cardiomyopathy and accurately predicted genotype status in early-stage HCM from cell type-resolved transcriptional profiles, revealing widespread genotype-driven remodeling. Together, our findings uncover multicellular, genotype-associated remodeling programs in HCM, providing insight into mechanisms unde
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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 articleBalakrishnan ID, Heymans ABM, Claggett B, et al., 2026,
Atrial Fibrillation in Genotyped Dilated Cardiomyopathy: Epidemiology, Risk Factors, and Outcomes: Insights From the SHaRe Registry.
, Circ Heart FailBACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in dilated cardiomyopathy (DCM) and is associated with adverse outcomes. However, the genetic determinants of AF risk and its prognostic significance across genotyped DCM subtypes remain unknown. METHODS: In this observational cohort study, we analyzed 3117 genotyped patients with DCM from the SHaRe (Sarcomeric Human Cardiomyopathy Registry). AF prevalence, incidence, and clinical characteristics were assessed by genotype. Patients were classified as genotype-positive [G(+)] if they had a pathogenic or likely pathogenic variant in a DCM-associated gene, and genotype-negative [G(-)] if genetic testing was negative. Factors associated with incident AF were evaluated using Cox regression. AF was modeled as a time-dependent variable to evaluate associations with clinical outcomes. RESULTS: Among 3117 genotyped patients with DCM (mean age, 48±15 years; 39% were female; and 35% were G[+]), 12.3% (n=384) had prevalent AF. Of 2491 patients without prevalent AF and with follow-up, 312 (12.5%) developed AF during a median of 4.5 years (interquartile range, 1.6-9.0). Among 2851 patients with follow-up, cumulative AF prevalence was 23.6%. LMNA had the highest AF incidence (7.6/100 patient-years) and cumulative AF prevalence (56.7%) and was the only genotype independently associated with incident AF compared with that in G(-) patients (hazard ratio, 5.52 [95% CI, 3.84-7.95]; P<0.001). TTN had an AF incidence of 2.1 per 100 patient-years and cumulative AF prevalence of 24.4%, comparable to that in G(-) patients. Older age, male sex, and prior heart failure hospitalization were also independently associated with incident AF. AF was independently associated with a higher risk of the composite clinical outcome (hazard ratio, 1.58 [95% CI, 1.29-1.94]; P<0.001), including heart failure, ventricular arrhythmias, and all-cause mortality. CONCLUSIONS: In this large genotyped DCM cohort, AF burden and incident
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Journal articleMazzarotto F, Ware J, 2026,
An updated evidence assessment of the genetic causes of dilated cardiomyopathy
, Circulation, ISSN: 0009-7322Background: Evidence of the diverse genetic architecture of dilated cardiomyopathy (DCM) continues to emerge and requires reassessment of the clinical relevance of implicated disease genes. Building on the 2019-2020 Clinical Genome Resource (ClinGen) evaluation, the DCM Gene Curation Expert Panel (GCEP) reconvened in 2024-2025 to conduct a reassessment of genes in DCM.Methods: The ClinGen semi-quantitative clinical validity classification framework was applied with specifications to DCM to classify genes into categories based upon strength of published evidence for a DCM phenotype. Previously curated genes were reassessed and newly reported gene-disease-mode of inheritance (MOI) relationships, termed “curations,” were evaluated.Results: Sixty-eight genes were evaluated, inclusive of 72 unique gene-disease-MOI relationships across 51 previously evaluated and 17 newly assessed genes. Thirty-five curations were classified as high evidence (16 Definitive, 10 Strong, 9 Moderate), increasing by 16 from the prior assessment. Nine newly assessed genes were classified as high evidence, including BAG5, FLII, LMOD2, MYLK3, MYZAP, NRAP, PPA2, PPP1R13L, and RPL3L. Twelve genes (11 newly appraised) were rated as high evidence with an autosomal recessive (AR) MOI. Five re-evaluated genes from 2019-2020 had clinically significant changes in classification. Except for JPH2, for which curation was modified to separate autosomal dominant (-AD) and -AR MOI curations, clinically significant changes involved upgrades from low to high evidence categories (PLEKHM2, PRDM16, TBX20, TNNI3K), demonstrating the robustness of the ClinGen gene curation process over time. An additional 29 gene-disease-MOI curations were classified as Limited, including six newly evaluated genes and one new MOI for a previously evaluated gene, MYBPC3-AR; four were classified as No Known Disease Relationship, and four remained Disputed. Four previously evaluated genes were curated for both AD and AR MOIs
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Journal articleKim JU, Kaza N, Zuhair M, et al., 2026,
Atrial Dyssynchrony and Bachmann Bundle Pacing: A Review.
, JAMA Cardiol, Vol: 11, Pages: 880-887IMPORTANCE: Cardiac dyssynchrony disrupts coordinated chamber activation and is associated with impaired cardiac function and adverse clinical outcomes. While ventricular dyssynchrony has been targeted through biventricular and conduction system pacing, atrial dyssynchrony remains underrecognized and largely untreated. OBSERVATIONS: Interatrial dyssynchrony commonly arises from delayed or impaired conduction through Bachmann bundle or from nonphysiological atrial pacing. It is associated with impaired ventricular filling and increased atrial arrhythmia risk. Importantly, conventional atrial pacing strategies may exacerbate rather than correct abnormal atrial activation. Bachmann bundle pacing represents a potential strategy to restore physiological atrial activation by engaging the dominant interatrial conduction pathway. Emerging data suggest that this approach may improve atrial synchrony, optimize atrioventricular timing, and reduce arrhythmia burden. CONCLUSIONS AND RELEVANCE: In this review, we summarize the mechanisms and clinical consequences of interatrial dyssynchrony and evaluate the role of Bachmann bundle pacing as a novel target for atrial resynchronization and a potential next step in physiological pacing. Further studies are required to define optimal implantation strategies and determine Bachmann bundle pacing's clinical impact.
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Journal articleRodero C, Curran L, Lanyon CW, et al., 2026,
Computational models show that functional remodeling, not anatomy, reshapes physiological determinants of cardiac performance in hypertrophic cardiomyopathy.
, J Mol Cell Cardiol, Vol: 218, Pages: 137-150Hypertrophic cardiomyopathy (HCM) is a condition characterized by variable patterns of myocardial hypertrophy. Progressive functional remodeling of material properties contributes to symptoms, disease progression, and variability in treatment response. However, it is not clear how these properties interact to determine cardiac performance and response to treatment. We quantified how cardiac anatomy variability, functional remodeling, and pharmacological treatment influence the relative importance of biophysical mechanisms that govern cardiac function. We built five four-chamber electromechanical heart models representing anatomical clusters. We performed global sensitivity analyses on 46 parameters across 32 outputs. We repeated this process 18 times to model different types of functional remodeling and two times to model mavacamten and aficamten. Across all representative HCM phenotypes, sensitivity profiles were preserved. Within the parameter ranges examined, ventricular afterload explained the largest share of variance in hemodynamic outputs across anatomies (up to 69%). Functional remodeling led to shifts in parameter importance, mostly when ventricular stiffness was increased. The modeling of pharmacological treatments led to modest but targeted changes, with mavacamten and aficamten producing comparable effects, particularly for outputs related to arterial pressures. Across major anatomical phenotypes of hypertrophic cardiomyopathy, functional remodeling, rather than anatomy alone, reshaped the relative importance of cellular, myocardial, and loading-related parameters, with the largest shifts under increased ventricular stiffness and under aficamten in obstructive physiology. These hypothesis-generating results suggest that the integration of biomarkers reflecting ventricular-arterial coupling, myocardial stiffness, and contractile state may help anticipate symptoms and treatment response in HCM.
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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 articleRowin EJ, Maron BJ, Siontis KC, et al., 2026,
International Experience With Implantable Cardioverter Defibrillators for the Prevention of Sudden Death in High-Risk Patients With Hypertrophic Cardiomyopathy.
, CirculationBACKGROUND: Implanted cardioverter-defibrillators (ICDs) have been used in patients with hypertrophic cardiomyopathy (HCM) to prevent sudden death, and have proven lifesaving for many patients. However, experience with ICD therapy has largely been derived from relatively small HCM cohorts confined to specific countries or regions of the world. Therefore, we sought to determine the effectiveness of ICDs in preventing sudden death due to life-threatening ventricular arrhythmias in a large international multicenter HCM population. METHODS: Databases from 25 HCM centers (8 in the United States, 9 in Europe, 4 in Asia, and 1 each in Australia, Africa, Mexico, and South America) were retrospectively interrogated to identify consecutive patients with HCM with ICDs (1992 to 2024) followed for 7±6 years (up to 32 years) for clinical outcomes. RESULTS: A total of 3387 patients were identified (63% men). They had a mean left ventricular thickness of 22±7 mm. The participants had received ICDs at a mean age of 47±17 years. Over follow-up, 550 patients (16%) experienced ≥1 appropriate ICD therapy (2.6%/y), including 86 of the 247 implanted for secondary prevention (35% [6.4%/y]) and 464 of the 3140 implanted for primary prevention (15% [2.2%/y]). Appropriate therapy occurred in the 464 primary prevention patients at a mean age of 49±17 years, with a median time to first appropriate therapy of 4 years after ICD implantation; 16% of these received their first appropriate therapy ≥10 years after implantation, and 47% experienced multiple interventions. Independent predictors of appropriate ICD therapy included unexplained syncope, left ventricular apical aneurysms, left ventricular systolic dysfunction, and nonsustained ventricular tachycardia on ambulatory monitoring. Of the 3140 primary prevention patients, 2946 survived (94%) and 194 died (6%) (0.8%/y), including 68 due to HCM (0.3%/y), predominantly of end-stage heart failure (n=43) or stroke (
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Journal articleVinther M, 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: The His-Alternative II Study.
, JACC Clin ElectrophysiolBACKGROUND: Cardiac resynchronization therapy (CRT) in patients with symptomatic heart failure and left bundle branch block (LBBB) can be achieved with biventricular pacing (BIV-CRT) or conduction system pacing (CSP-CRT). OBJECTIVES: The present study examined if CSP-CRT was feasible and noninferior to BIV-CRT. METHODS: A total of 150 patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤35%, and LBBB (Strauss criteria) were included. Patients were randomized 1:2 to either BiV-CRT or CSP-CRT (HIS-CRT or LBB-CRT) and followed for 6 months. The primary endpoint was the relative change in left ventricular end-systolic volume (LVESV). Two patients withdrew their consent before implant. RESULTS: At implantation, 15 patients (15 %) crossed over from the CSP-CRT group to the BiV-CRT group and 1 patient crossed over from BiV-CRT to the CSP-CRT group. Accordingly, 85 patients (57 %) were treated with CSP-CRT (26 His-CRT, 59 patients LBB-CRT) and 63 patients (43 %) with BiV-CRT. For the primary endpoint, intention-to-treat 6-month follow-up LVESV decreased by 35% ± 22% with CSP-CRT vs 34% ± 22% with BiV-CRT (between-group differences 0.9%, 95% CI: -6.0% to 7.8%; P < 0.01 for noninferiority, P = 0.80 for superiority). Furthermore, LVEF increased by 14% ± 8% with CSP-CRT vs 14% ± 9% with BiV-CRT (P = NS). QRS duration shortening (-31 ± 22 ms vs -31 ± 21 ms), 6-min walking distance increase (37 ± 53 m vs 24 ± 48 m), Minnesota Living with Heart Failure score reduction (-16 ± 18 vs -13 ± 15), NYHA functional class improvement (-0.6 ± 0.6 vs -0.6 ± 0.7), and N-terminal pro-B-type natriuretic peptide reductions (-72 ± 152 pmol/l vs -110 ± 116 pmol/l) were similar between groups. CONCLUSIONS: In heart failure patients with LBBB, CSP-CRT was noninferior to BiV-CRT in reducing LVESV and both treatment modalities provided similar and excellent improvement
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Journal articleSamways JW, Ali N, Arnold AD, et al., 2026,
Non-Invasive Methods for Identifying Electrical Responders to Conduction System Pacing Cardiac Resynchronization Therapy.
, Pacing Clin ElectrophysiolBACKGROUND: Conduction system pacing (CSP) is an emerging alternative modality of cardiac resynchronization therapy (CRT). However, not all patients obtain electrical resynchronization with CSP, there is a clinical need for reliable non-invasive predictors of response. We aimed to assess the ability of several non-invasive modalities to predict electrical resynchronization with CSP-CRT. METHODS: Patients with standard heart failure CRT indications (excluding right-bundle branch block) underwent CSP-CRT using His-bundle and left-bundle branch pacing. Electrical resynchronization was defined as a >10 ms reduction in left ventricular activation time or conversion to a physiological left ventricular activation pattern on non-invasive multi-electrode mapping. We assessed whether 12-lead ECG morphology, vector electrocardiogram (VCG) derived QRS area, Ultra High Frequency (UHF)-ECG parameters or MRI scar burden predicted electrical resynchronization. RESULTS: Thirty four patients were analyzed (mean age 69±10 years; 82% male; LVEF 30±6%; QRS duration 161±23 ms; 32% ischemic cardiomyopathy). Electrical resynchronization was achieved in 24/34 (71%; 95%CI 53-85). Strauss criteria positivity on 12-lead ECG yielded a positive predictive value (PPV) of 83% (95%CI 61-95%) and negative predictive value (NPV) of 55% (95%CI 23-83%). VCG QRS area >100µVs demonstrated PPV 100% (95% CI 81-100%) and NPV 73% (95%CI 85-100%). UHF-ECG e-DYS >50 ms gave PPV 93% (95%CI 66-100%) and NPV 47% (23%-72%); >60 ms gave PPV 90% (95%CI 66-100%) and NPV 38% (95%CI 18-62%). MRI scar burden <15% resulted in PPV 88% (95%CI 64-99%) and NPV 56% (95%CI 21-86%). Lines of propagation discontinuity on multi-electrode mapping showed PPV 100% (95%CI 85-100%) and NPV 83% (95%CI 52-98%). CONCLUSIONS: Multiple non-invasive markers, including QRS morphology, VCG QRS area, UHF-ECG e-DYS, MRI scar burden showed potential to identify patients who are likely
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