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Ventricular tachycardia (VT) is a life-threatening heart rhythm and has long posed a complex challenge in the field of cardiology. Recent developments in advanced imaging modalities have aimed to improve comprehension of underlying arrhythmic substrate for VT. To this extent, high-resolution cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) have emerged as tools for accurately visualizing and characterizing scar tissue, fibrosis, and other critical structural abnormalities within the heart, providing novel insights into VT triggers and substrate. However, clinical implementation of knowledge derived from these advanced imaging techniques in improving VT treatment and guiding invasive therapeutic strategies continues to pose significant challenges. A pivotal concern lies in the absence of standardized imaging protocols and analysis methodologies, resulting in a large variance in data quality and consistency. Furthermore, the clinical significance and outcomes associated with VT substrate characterization through CMR and CCT remain dynamic and subject to ongoing evolution. This highlights the need for refinement of these techniques before their reliable integration into routine patient care can be realized. The primary objectives of this study are twofold: firstly, to provide a comprehensive overview of the studies conducted over the last 15 years, summarizing the current available literature on imaging-based assessment of VT substrate. Secondly, to critically analyze and evaluate the selected studies, with the aim of providing valuable insights that can inform current clinical practice and future research.
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BACKGROUND: Among patients with nephroblastoma, those with bilateral disease are a unique population where maximising tumour control must be balanced with preserving renal parenchyma. METHODS: The SIOP 2001 protocol recommended surgery after neoadjuvant cycle(s) of Dactinomycin and Vincristine (AV) with response-adapted intensification, if needed. Adjuvant treatment was given based on the lesion with the worst histology. RESULTS: Three hundred and twenty seven patients with stage V disease were evaluable: 174 had bilateral Wilms tumour (BWT), 101 unilateral WT and contralateral nephroblastomatosis (NB) and 52 bilateral nephroblastomatosis. In these three groups, the estimated 5y-EFS was 76.1%, 84.6%, and 74.9%, respectively. AV chemotherapy alone was the successful chemotherapy for 58.7% of all the patients and 65.6% of the non-metastatic patients. Among the 174 patients with BWT, 149 (88.2%) had at least one nephron-sparing surgery. Twenty of 61 bilateral stage I patients were treated with four-week AV postoperatively achieving 94.4% 5y-EFS. At last follow-up, 87% of patients had normal renal function. CONCLUSIONS: This study demonstrates that AV without anthracyclines is sufficient to achieve NSS and good survival in the majority of patients. For patients with bilateral stage I WT and intermediate risk histology, only four weeks adjuvant AV seems to be sufficient. CLINICAL TRIAL REGISTRATION: NCT00047138.
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Protocolos de Quimioterapia Combinada Antineoplásica , Dactinomicina , Neoplasias Renales , Vincristina , Tumor de Wilms , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Dactinomicina/administración & dosificación , Dactinomicina/uso terapéutico , Neoplasias Renales/patología , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Neoplasias Renales/terapia , Terapia Neoadyuvante , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/tratamiento farmacológico , Neoplasias Primarias Múltiples/cirugía , Nefrectomía/métodos , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Tumor de Wilms/patología , Tumor de Wilms/tratamiento farmacológico , Tumor de Wilms/cirugía , Tumor de Wilms/terapiaRESUMEN
The efficacy of an implantable cardioverter-defibrillator (ICD) in patients with a non-ischaemic cardiomyopathy for primary prevention of sudden cardiac death is increasingly debated. We developed a multimodal deep learning model for arrhythmic risk prediction that integrated late gadolinium enhanced (LGE) cardiac magnetic resonance imaging (MRI), electrocardiography (ECG) and clinical data. Short-axis LGE-MRI scans and 12-lead ECGs were retrospectively collected from a cohort of 289 patients prior to ICD implantation, across two tertiary hospitals. A residual variational autoencoder was developed to extract physiological features from LGE-MRI and ECG, and used as inputs for a machine learning model (DEEP RISK) to predict malignant ventricular arrhythmia onset. In the validation cohort, the multimodal DEEP RISK model predicted malignant ventricular arrhythmias with an area under the receiver operating characteristic curve (AUROC) of 0.84 (95% confidence interval (CI) 0.71-0.96), a sensitivity of 0.98 (95% CI 0.75-1.00) and a specificity of 0.73 (95% CI 0.58-0.97). The models trained on individual modalities exhibited lower AUROC values compared to DEEP RISK [MRI branch: 0.80 (95% CI 0.65-0.94), ECG branch: 0.54 (95% CI 0.26-0.82), Clinical branch: 0.64 (95% CI 0.39-0.87)]. These results suggest that a multimodal model achieves high prognostic accuracy in predicting ventricular arrhythmias in a cohort of patients with non-ischaemic systolic heart failure, using data collected prior to ICD implantation.
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Arritmias Cardíacas , Cardiomiopatías , Desfibriladores Implantables , Electrocardiografía , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Persona de Mediana Edad , Cardiomiopatías/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Anciano , Inteligencia Artificial , Aprendizaje Profundo , Muerte Súbita Cardíaca/prevención & control , Muerte Súbita Cardíaca/etiología , Medición de Riesgo/métodos , Factores de Riesgo , Curva ROCRESUMEN
Purpose To perform a qualitative and quantitative evaluation of the novel image-navigated (iNAV) 3D late gadolinium enhancement (LGE) cardiac MRI imaging strategy in comparison with the conventional diaphragm-navigated (dNAV) 3D LGE cardiac MRI strategy for the assessment of left atrial fibrosis in atrial fibrillation (AF). Materials and Methods In this prospective study conducted between April and September 2022, 26 consecutive participants with AF (mean age, 61 ± 11 years; 19 male) underwent both iNAV and dNAV 3D LGE cardiac MRI, with equivalent spatial resolution and timing in the cardiac cycle. Participants were randomized in the acquisition order of iNAV and dNAV. Both, iNAV-LGE and dNAV-LGE images were analyzed qualitatively using a 5-point Likert scale and quantitatively (percentage of atrial fibrosis using image intensity ratio threshold 1.2), including testing for overlap in atrial fibrosis areas by calculating Dice score. Results Acquisition time of iNAV was significantly lower compared with dNAV (4.9 ± 1.1 minutes versus 12 ± 4 minutes, P < .001, respectively). There was no evidence of a difference in image quality for all prespecified criteria between iNAV and dNAV, although dNAV was the preferred image strategy in two-thirds of cases (17/26, 65%). Quantitative assessment demonstrated that mean fibrosis scores were lower for iNAV compared with dNAV (12 ± 8% versus 20 ± 12%, P < .001). Spatial correspondence between the atrial fibrosis maps was modest (Dice similarity coefficient, 0.43 ± 0.15). Conclusion iNAV-LGE acquisition in individuals with AF was more than twice as fast as dNAV acquisition but resulted in a lower atrial fibrosis score. The differences between these two strategies might impact clinical interpretation. ©RSNA, 2024.
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Fibrilación Atrial , Diafragma , Anciano , Humanos , Masculino , Persona de Mediana Edad , Fibrilación Atrial/diagnóstico , Medios de Contraste , Gadolinio , Atrios Cardíacos/diagnóstico por imagen , Imagen por Resonancia Magnética , Estudios Prospectivos , FemeninoRESUMEN
BACKGROUND: Chronic total coronary occlusions (CTO) substantially increase the risk for sudden cardiac death. Among patients with chronic ischemic heart disease at risk for sudden cardiac death, an implantable cardioverter defibrillator (ICD) is the favored therapy for primary prevention of sudden cardiac death. This study sought to investigate the impact of CTOs on the risk for appropriate ICD shocks and mortality within a nationwide prospective cohort. METHODS AND RESULTS: This is a subanalysis of the nationwide Dutch-Outcome in ICD Therapy (DO-IT) registry of primary prevention ICD recipients in The Netherlands between September 2014 and June 2016 (n=1442). We identified patients with chronic ischemic heart disease (n=663) and assessed available coronary angiograms for CTO presence (n=415). Patients with revascularized CTOs were excluded (n=79). The primary end point was the composite of all-cause mortality and appropriate ICD shocks. Clinical follow-up was conducted for at least 2 years. A total of 336 patients were included, with an average age of 67±9 years, and 20.5% was female (n=69). An unrevascularized CTO was identified in 110 patients (32.7%). During a median follow-up period of 27 months (interquartile range, 24-32), the primary end point occurred in 21.1% of patients with CTO (n=23) compared with 11.9% in patients without CTO (n=27; P=0.034). Corrected for baseline characteristics including left ventricular ejection fraction, and the presence of a CTO was an independent predictor for the primary end point (hazard ratio, 1.82 [95% CI, 1.03-3.22]; P=0.038). CONCLUSIONS: Within this nationwide prospective registry of primary prevention ICD recipients, the presence of an unrevascularized CTO was an independent predictor for the composite outcome of all-cause mortality and appropriate ICD shocks.
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Oclusión Coronaria , Desfibriladores Implantables , Humanos , Femenino , Persona de Mediana Edad , Anciano , Oclusión Coronaria/complicaciones , Oclusión Coronaria/diagnóstico por imagen , Oclusión Coronaria/terapia , Arritmias Cardíacas , Desfibriladores Implantables/efectos adversos , Volumen Sistólico , Incidencia , Función Ventricular Izquierda , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Sistema de Registros , Factores de RiesgoRESUMEN
International guidelines recommend implantation of an implantable cardioverter-defibrillator (ICD) in non-ischaemic cardiomyopathy (NICM) patients with a left ventricular ejection fraction (LVEF) below 35% despite optimal medical therapy and a life expectancy of more than 1 year with good functional status. We propose refinement of these recommendations in patients with NICM, with careful consideration of additional risk parameters for both arrhythmic and non-arrhythmic death. These additional parameters include late gadolinium enhancement on cardiac magnetic resonance imaging and genetic testing for high-risk genetic variants to further assess arrhythmic risk, and age, comorbidities and sex for assessment of non-arrhythmic mortality risk. Moreover, several risk modifiers should be taken into account, such as concomitant arrhythmias that may affect LVEF (atrial fibrillation, premature ventricular beats) and resynchronisation therapy. Even though currently no valid cut-off values have been established, the proposed approach provides a more careful consideration of risks that may result in withholding ICD implantation in patients with low arrhythmic risk and substantial non-arrhythmic mortality risk.
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This review systematically describes the application of in vivo mouse models in studying cutaneous T-cell lymphoma (CTCL), a complex hematological neoplasm. It highlights the diverse research approaches essential for understanding CTCL's intricate pathogenesis and evaluating potential treatments. The review categorizes various mouse models, including xenograft, syngeneic transplantation, and genetically engineered mouse models (GEMMs), emphasizing their contributions to understanding tumor-host interactions, gene functions, and studies on drug efficacy in CTCL. It acknowledges the limitations of these models, particularly in fully replicating human immune responses and early stages of CTCL. The review also highlights novel developments focusing on the potential of skin-targeted GEMMs in studying natural skin lymphoma progression and interactions with the immune system from onset. In conclusion, a balanced understanding of these models' strengths and weaknesses are essential for accelerating the deciphering of CTCL pathogenesis and developing treatment methods. The GEMMs engineered to target specifically skin-homing CD4+ T cells can be the next top mouse models that pave the way for exploring the effects of CTCL-related genes.
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Trastuzumab and trastuzumab-based treatments are the standard of care for breast cancer patients who overexpress the human epidermal growth factor receptor 2 (HER2). However, patients often develop resistance to trastuzumab via signaling from alternative growth factor receptors that converge to activate guanine nucleotide exchange factors (GEFs) that in turn activate the Rho GTPases Rac and Cdc42. Since Rac and Cdc42 have been implicated in high tumor grade and therapy resistance, inhibiting the activity of Rac and Cdc42 is a rational strategy to overcome HER2-targeted therapy resistance. Therefore, our group developed MBQ-167, a dual Rac/Cdc42 inhibitor with IC50s of 103 nM and 78 nM for Rac and Cdc42, respectively, which is highly effective in reducing cell and tumor growth and metastasis in breast cancer cell and mouse models. Herein, we created a trastuzumab resistant variant of the SKBR3 HER2 positive breast cancer cell line and show that Rac activation is a central mechanism in trastuzumab resistance. Next, we tested the potential of targeting MBQ-167 to HER2 overexpressing trastuzumab-resistant cell lines in vitro, and show that MBQ-167, but not trastuzumab, reduces cell viability and induces apoptosis. When MBQ-167 was targeted to mammary fatpad tumors established from HER2 overexpressing cells via immunoliposomes functionalized with trastuzumab, MBQ-167 and MBQ-167-loaded liposomes show equal efficacy in reducing the viability of trastuzumab-resistant cells, inhibiting tumor growth in mouse xenografts, and reducing metastasis to lungs and liver. This study demonstrates the efficacy of MBQ-167 as an alternative therapeutic in HER2 overexpressing cancers, delivered either in free form or in liposomes.
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BACKGROUND: Patient-specific 3D models of neuroblastoma and relevant anatomy are useful tools for surgical planning. However, these models do not represent the heterogenous biology of neuroblastoma. This heterogeneity is visualized with the ADC and 123I-MIGB-SPECT-CT imaging. Combining these multi-modal data into preoperative 3D heatmaps, may allow differentiation of the areas of vital and non-vital tumor tissue. We developed a workflow to create multi-modal preoperative 3D models for neuroblastoma surgery. METHODS: We included 7 patients who underwent neuroblastoma surgery between 2022 and 2023. We developed 3D models based on the contrast enhanced T1-weighted MRI scans. Subsequently, we aligned the corresponding ADC and 123I-MIBG-SPECT-CT images using rigid transformation. We estimated registration precision using the Dice score and the target registration error (TRE). 3D heatmaps were computed based on ADC and 123I-MIBG uptake. RESULTS: The registration algorithm had a median Dice score of 0.81 (0.75-0.90) for ADC and 0.77 (0.65-0.91) for 123I-MIBG-SPECT. For the ADC registration, the median TRE of renal vessels was 4.90 mm (0.86-10.18) and of the aorta 4.67 mm (1.59-12.20). For the 123I -MIBG-SPECT imaging the TRE of the renal vessels was 5.52 mm (1.71-10.97) and 5.28 mm (3.33-16.77) for the aorta. CONCLUSIONS: We successfully developed a registration workflow to create multi-modal 3D models which allows the surgeon to visualize the tumor and its biological behavior in relation to the surrounding tissue. Future research will include linking of pathological results to imaging data, to validate these multi-modal 3D models. LEVEL OF EVIDENCE: Level IV. TYPE OF STUDY: Clinical Research.
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Imagenología Tridimensional , Neuroblastoma , Humanos , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/cirugía , Neuroblastoma/patología , Niño , Preescolar , Femenino , Masculino , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Lactante , Estudios Retrospectivos , Radiofármacos , 3-Yodobencilguanidina , Algoritmos , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Multimodal/métodosRESUMEN
BACKGROUND: Surgical treatment of pediatric chest wall tumors requires accurate surgical planning and tumor localization to achieve radical resections while sparing as much healthy tissue as possible. Augmented Reality (AR) could facilitate surgical decision making by improving anatomical understanding and intraoperative tumor localization. We present our clinical experience with the use of an AR system for intraoperative tumor localization during chest wall resections. Furthermore, we present the pre-clinical results of a new registration method to improve our conventional AR system. METHODS: From January 2021, we used the HoloLens 2 for pre-incisional tumor localization during all chest wall resections inside our center. A patient-specific 3D model was projected onto the patient by use of a five-point registration method based on anatomical landmarks. Furthermore, we developed and pre-clinically tested a surface matching method to allow post-incisional AR guidance by performing registration on the exposed surface of the ribs. RESULTS: Successful registration and holographic overlay were achieved in eight patients. The projection seemed most accurate when landmarks were positioned in a non-symmetric configuration in proximity to the tumor. Disagreements between the overlay and expected tumor location were mainly due to user-dependent registration errors. The pre-clinical tests of the surface matching method proved the feasibility of registration on the exposed ribs. CONCLUSIONS: Our results prove the applicability of AR guidance for the pre- and post-incisional localization of pediatric chest wall tumors during surgery. The system has the potential to enable intraoperative 3D visualization, hereby facilitating surgical planning and management of chest wall resections. LEVEL OF EVIDENCE: IV TYPE OF STUDY: Treatment Study.
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Realidad Aumentada , Neoplasias Torácicas , Pared Torácica , Humanos , Pared Torácica/cirugía , Neoplasias Torácicas/cirugía , Neoplasias Torácicas/patología , Niño , Cirugía Asistida por Computador/métodos , Femenino , Masculino , Imagenología Tridimensional , Preescolar , AdolescenteRESUMEN
Background and purpose: Individual elective lymph node irradiation instead of elective neck irradiation is a new concept for head-and-neck cancer (HNC) patients developed for the Magnetic Resonance Image guided linear accelerator (MR-linac). To prepare this, the detectability, volume changes and intra-fraction motion of elective lymph nodes on the MR-linac was assessed. Materials and methods: A total of 15 HNC patients underwent diagnostic pre-treatment MRI. Additionally, two MR-linac scans were obtained with a 10-minute time difference in the first week of radiation treatment. Elective lymph node contours inside lymph node levels (Ib-V) were segmented on the pre-treatment MRI and the MR-linac scans and compared on number and maximal transversal diameter. Intra-fraction motion of elective lymph nodes on the MR-linac was estimated using Center of Mass (COM) distances and incremental isotropic expansion of lymph node segmentations. Results: Of all 679 detected lymph nodes on the pre-treatment MRI, eight lymph nodes were not detectable on the first MR-linac scan and 16 new lymph nodes were detected. Lymph node diameters between the pre-treatment MRI scan and the MR-linac scan varied from -0.19 to + 0.13 mm. COM distances varied from 1.2 to 1.7 mm and lymph node contours had to be expanded with 3 mm. Conclusions: Nearly all elective lymph nodes were detectable on the 1.5T MR-linac scan with no major changes in target volumes compared to the pre-treatment MRI. Simulated intra-fraction motion during the MR-linac scans was smaller than the 5-mm margin that will be used in the first elective lymph node radiation treatment.
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OBJECTIVE: This study aims to determine the added value of a geometrically accurate diffusion-weighted (DW-) MRI sequence on the accuracy of gross tumor volume (GTV) delineations, using pathological tumor delineations as a ground truth. METHODS: Sixteen patients with laryngeal or hypopharyngeal carcinoma were included. After total laryngectomy, the specimen was cut into slices. Photographs of these slices were stacked to create a 3D digital specimen reconstruction, which was registered to the in vivo imaging. The pathological tumor (tumorHE) was delineated on the specimen reconstruction. Six observers delineated all tumors twice: once with only anatomical MR imaging, and once (a few weeks later) when DW sequences were also provided. The majority voting delineation of session one (GTVMRI) and session two (GTVDW-MRI), as well as the clinical target volumes (CTVs), were compared to the tumorHE. RESULTS: The mean tumorHE volume was 11.1 cm3, compared to a mean GTVMRI volume of 18.5 cm3 and a mean GTVDW-MRI volume of 15.7 cm3. The median sensitivity (tumor coverage) was comparable between sessions: 0.93 (range: 0.61-0.99) for the GTVMRI and 0.91 (range: 0.53-1.00) for the GTVDW-MRI. The CTV volume also decreased when DWI was available, with a mean CTVMR of 47.1 cm3 and a mean CTVDW-MRI of 41.4 cm3. Complete tumor coverage was achieved in 15 and 14 tumors, respectively. CONCLUSION: GTV delineations based on anatomical MR imaging tend to overestimate the tumor volume. The availability of the geometrically accurate DW sequence reduces the GTV overestimation and thereby CTV volumes, while maintaining acceptable tumor coverage.
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Imagen de Difusión por Resonancia Magnética , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Humanos , Neoplasias Hipofaríngeas/diagnóstico por imagen , Neoplasias Hipofaríngeas/patología , Neoplasias Laríngeas/diagnóstico por imagen , Neoplasias Laríngeas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Carga Tumoral , LaringectomíaRESUMEN
BACKGROUND: Dermoscopy is known to increase the diagnostic accuracy of pigmented skin lesions (PSLs) when used by trained professionals. The effect of dermoscopy training on the diagnostic ability of dermal therapists (DTs) has not been studied so far. OBJECTIVES: This study aimed to investigate whether DTs, in comparison with general practitioners (GPs), benefited from a training programme including dermoscopy, in both their ability to differentiate between different forms of PSL and to assign the correct therapeutic strategy. METHODS: In total, 24 DTs and 96 GPs attended a training programme on PSLs. Diagnostic skills as well as therapeutic strategy were assessed, prior to the training (pretest) and after the training (post-test) using clinical images alone, as well as after the addition of dermatoscopic images (integrated post-test). Bayesian hypothesis testing was used to determine statistical significance of differences between pretest, post-test and integrated post-test scores. RESULTS: Both the DTs and the GPs demonstrated benefit from the training: at the integrated post-test, the median proportion of correctly diagnosed PSLs was 73% (range 30-90) for GPs and 63% (range 27-80) for DTs. A statistically significant difference between pretest results and integrated test results was seen, with a Bayes factor > 100. At 12 percentage points higher, the GPs outperformed DTs in the accuracy of detecting PSLs. CONCLUSIONS: The study shows that a training programme focusing on PSLs while including dermoscopy positively impacts detection of PSLs by DTs and GPs. This training programme could form an integral part of the training of DTs in screening procedures, although additional research is needed.
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Competencia Clínica , Dermoscopía , Médicos Generales , Dermoscopía/educación , Dermoscopía/métodos , Humanos , Médicos Generales/educación , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/diagnóstico por imagen , Femenino , Masculino , Dermatólogos/educación , Dermatólogos/estadística & datos numéricos , Educación Médica Continua/métodos , AdultoRESUMEN
Background: A chronic total coronary occlusion (CTO) is associated with ventricular arrhythmias (VA) in patients with an implantable cardioverter-defibrillator (ICD). Limited data is available on the incidence of VA in CTO patients without an ICD. Objectives: To investigate the incidence of sustained VA in CTO patients after successful CTO revascularization and in patients with untreated CTO or failed CTO revascularization. Methods: Prospective, multicenter observational pilot study including CTO patients who were not eligible for an ICD and had a left ventricular ejection fraction >35 %. We enrolled patients with a successful CTO revascularization (group A) and patients with untreated CTO or failed CTO revascularization (group B). All patients received an implantable loop recorder with remote monitoring. The primary endpoint was sustained VA. Results: Ninety patients were enrolled (mean age 63 ± 10 years, 83.3 % man, mean LVEF 55 ± 8 %). Group A (n = 45) had a higher prevalence of CTO in the left anterior descending artery in comparison to group B (n = 45) (28.9 % versus 4.4 %, P = 0.002). Other baseline characteristics were similar. During a median follow-up time of 26 months (IQR, 19-35), five patients (5.6 %) had a sustained VA. There was no difference in the incidence of sustained VA between groups (3-year cumulative event rate: 8.8 % (group A) versus 4.5 % (Group B), log-rank P = 0.71). Conclusion: Patients with an CTO, who do not qualify for an ICD, have a substantial risk of sustained VA. In our study the incidence was not different between patients with revascularized and those with untreated CTO.
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Cardiac resynchronization therapy (CRT) is an established treatment for heart failure patients with left ventricular dysfunction and a left bundle branch block. However, its impact on right ventricular (RV) function remains uncertain. This cardiac magnetic resonance imaging study found that CRT did not improve RV volumes and function, and CRT-off during follow-up had an immediate detrimental effect on the RV, which may suggest potential unfavorable RV remodeling with RV pacing during CRT.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Humanos , Terapia de Resincronización Cardíaca/métodos , Bloqueo de Rama/terapia , Ventrículos Cardíacos/diagnóstico por imagen , Resultado del Tratamiento , Insuficiencia Cardíaca/terapia , Función Ventricular Izquierda , Electrocardiografía/métodosRESUMEN
BACKGROUND: Risk stratification for ventricular arrhythmias currently relies on static measurements that fail to adequately capture dynamic interactions between arrhythmic substrate and triggers over time. We trained and internally validated a dynamic machine learning (ML) model and neural network that extracted features from longitudinally collected electrocardiograms (ECG), and used these to predict the risk of malignant ventricular arrhythmias. METHODS: A multicentre study in patients implanted with an implantable cardioverter-defibrillator (ICD) between 2007 and 2021 in two academic hospitals was performed. Variational autoencoders (VAEs), which combine neural networks with variational inference principles, and can learn patterns and structure in data without explicit labelling, were trained to encode the mean ECG waveforms from the limb leads into 16 variables. Supervised dynamic ML models using these latent ECG representations and clinical baseline information were trained to predict malignant ventricular arrhythmias treated by the ICD. Model performance was evaluated on a hold-out set, using time-dependent receiver operating characteristic (ROC) and calibration curves. FINDINGS: 2942 patients (61.7 ± 13.9 years, 25.5% female) were included, with a total of 32,129 ECG recordings during a mean follow-up of 43.9 ± 35.9 months. The mean time-varying area under the ROC curve for the dynamic model was 0.738 ± 0.07, compared to 0.639 ± 0.03 for a static (i.e. baseline-only model). Feature analyses indicated dynamic changes in latent ECG representations, particularly those affecting the T-wave morphology, were of highest importance for model predictions. INTERPRETATION: Dynamic ML models and neural networks effectively leverage routinely collected longitudinal ECG recordings for personalised and updated predictions of malignant ventricular arrhythmias, outperforming static models. FUNDING: This publication is part of the project DEEP RISK ICD (with project number 452019308) of the research programme Rubicon which is (partly) financed by the Dutch Research Council (NWO). This research is partly funded by the Amsterdam Cardiovascular Sciences (personal grant F.V.Y.T).