RESUMEN
OBJECTIVE: The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. METHODS: STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. RESULTS: A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2 ± 9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr < 33.45% had more adverse long-term outcomes (log rank p < .0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p = .010). CONCLUSION: Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.
Asunto(s)
Ecocardiografía , Atrios Cardíacos , Lupus Eritematoso Sistémico , Humanos , Femenino , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Pronóstico , Ecocardiografía/métodos , Persona de Mediana Edad , Adulto , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/complicaciones , Hipertensión Arterial Pulmonar/etiología , Hipertensión Arterial Pulmonar/sangre , Función del Atrio Derecho/fisiología , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/etiología , Estudios de SeguimientoRESUMEN
Atrial fibrillation is the most common cardiac arrhythmia, leading to progressive dilation of cardiac chambers, abnormal contraction patterns of the atria and ventricles and, potentially, atrioventricular valvular insufficiency. Moreover, heart failure with preserved ejection fraction is often present and closely intertwined with disease initiation and progression. Surgical valve repair with a true-sized ring annuloplasty is a well-established treatment option in atrial functional mitral regurgitation. While early results are good, recent studies have brought the durability of this repair approach into question, highlighting the need for further refinement of the surgical strategy. In particular, repair strategies that simultaneously target the mitral valve as well as the left ventricle could provide improved repair durability.
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Anuloplastia de la Válvula Mitral , Insuficiencia de la Válvula Mitral , Humanos , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/diagnóstico , Anuloplastia de la Válvula Mitral/métodos , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/cirugía , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Válvula Mitral/cirugía , Resultado del Tratamiento , Implantación de Prótesis de Válvulas Cardíacas/métodosRESUMEN
We investigated the modulatory effects of aldosterone on atrial remodeling induced by an abdominal aorto-venocaval shunt (AVS) in rats, as patients with primary hyperaldosteronism are suggested to have a higher risk of developing atrial fibrillation (AF). The rats were divided into four groups based on the basis of whether they underwent AVS surgery, received aldosterone using an intraperitoneally implanted osmotic minipump, or both. Aldosterone was started at 0.5 µg/h during the AVS surgery, and morphological and electrophysiological assessments were performed four weeks after AVS creation. The atrial structural changes induced by AVS, including atrial cell hypertrophy and fibrosis, were not modulated by aldosterone, whereas P-wave duration was longer in aldosterone-treated AVS rats than in non-treated rats. Although the average AF duration induced by burst pacing was 10-25 s in the untreated, aldosterone-treated, and AVS rats, the AF duration was approximately 100 s in the aldosterone-treated AVS rats. Meanwhile, there was no significant difference in the atrial effective refractory period among the four experimental groups. Notably, premature atrial contractions (PAC) were frequently observed in aldosterone-treated sham rats, while paroxysmal AF, in addition to PAC, was detected in aldosterone-treated AVS rats, which was not induced in non-treated AVS rats. These findings suggest that aldosterone robustly promotes AF, particularly in the presence of chronic volume overload.
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Aldosterona , Fibrilación Atrial , Atrios Cardíacos , Animales , Aldosterona/sangre , Fibrilación Atrial/etiología , Fibrilación Atrial/fisiopatología , Masculino , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/patología , Remodelación Atrial/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
Mitral regurgitation (MR) is associated with morphological and functional alterations of left atrium (LA) and ventricle (LV), possibly inducing LA-LV misalignment. We aimed to: (1) characterize angulation between LA and mitral annulus from conventional cine MRI data and feature-tracking (FT) contours, (2) assess their associations with functional capacity in MR patients, as assessed by oxygen consumption (peak-VO2) and minute ventilation to carbon dioxide production (VE/VCO2) slope, in comparison with MRI LA/LV strain indices. Thirty-two asymptomatic primary MR patients (56 [40; 66] years, 12 women) underwent cardiac MRI resulting in LA/LV conventional FT-derived strain indices. Then, end-diastolic angles were derived from FT LA contours: (1) α, centered on the LA centre of mass and defined by mitral valve extremities, (2) γ, centered on the mitral ring anterior/lateral side, and defined by LA centre and the other extremity of the mitral ring. Cardiopulmonary exercise testing with simultaneous echocardiography were also performed; peak-VO2 and VE/VCO2 slope were measured. While peak-VO2 and VE/VCO2 slope were not correlated to LA/LV strains, they were significantly associated with angles (α: r = 0.50, p = 0.003 and r = - 0.52, p = 0.003; γ: r = - 0.53, p = 0.002 and r = 0.52, p = 0.003; respectively), independently of age and gender (R2 ≥ 0.29, p ≤ 0.03). In primary MR, the new LA/mitral annulus angles, computed directly from standard-of-care MRI, are better correlated to exercise tolerance than conventional LA/LV strain.
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Ventrículos Cardíacos , Imagen por Resonancia Cinemagnética , Insuficiencia de la Válvula Mitral , Humanos , Femenino , Masculino , Persona de Mediana Edad , Imagen por Resonancia Cinemagnética/métodos , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Anciano , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Adulto , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Prueba de Esfuerzo/métodos , Consumo de Oxígeno , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/fisiopatología , Ecocardiografía/métodosRESUMEN
Atrial Myxoma is the most common primary benign tumour of the heart, commonly found in the left atrium. It typically presents in young females with characteristic features such as, constitutional symptoms, chest pain, and cardiac murmurs. However, atypical presentations can occur; causing a diagnostic challenge. This case report describes a 75-year-old male who visited the cardiology outpatient department of Dow Institute of Cardiology, Karachi on 18th April, 2023 with a left-sided atrial myxoma in late adulthood without typical features including constitutional symptoms, chest pain, syncope, dizziness, digital clubbing or neurologic findings. Further discussed are the diagnostic techniques used to find the tumour and the treatment strategy. This case report highlights the need for cardiologists to consider Atrial Myxoma as a potential diagnosis, even in the absence of typical symptoms, in elderly male population.
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Atrios Cardíacos , Neoplasias Cardíacas , Mixoma , Humanos , Mixoma/cirugía , Mixoma/diagnóstico , Masculino , Neoplasias Cardíacas/cirugía , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/diagnóstico por imagen , Anciano , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/patología , EcocardiografíaRESUMEN
BACKGROUND: Atrial fibrillation has an estimated prevalence of 1.5-2%, making it the most common cardiac arrhythmia. The processes that cause and sustain the disease are still not completely understood. An association between atrial fibrillation and systemic, as well as local, inflammatory processes has been reported. However, the exact mechanisms underlying this association have not been established. While it is understood that inflammatory macrophages can influence cardiac electrophysiology, a direct, causative relationship to atrial fibrillation has not been described. This study investigated the pro-arrhythmic effects of activated M1 macrophages on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes, to propose a mechanistic link between inflammation and atrial fibrillation. METHODS: Two hiPSC lines from healthy individuals were differentiated to atrial cardiomyocytes and M1 macrophages and integrated in an isogenic, pacing-free, atrial fibrillation-like coculture model. Electrophysiology characteristics of cocultures were analysed for beat rate irregularity, electrogram amplitude and conduction velocity using multi electrode arrays. Cocultures were additionally treated using glucocorticoids to suppress M1 inflammation. Bulk RNA sequencing was performed on coculture-isolated atrial cardiomyocytes and compared to meta-analyses of atrial fibrillation patient transcriptomes. RESULTS: Multi electrode array recordings revealed M1 to cause irregular beating and reduced electrogram amplitude. Conduction analysis further showed significantly lowered conduction homogeneity in M1 cocultures. Transcriptome sequencing revealed reduced expression of key cardiac genes such as SCN5A, KCNA5, ATP1A1, and GJA5 in the atrial cardiomyocytes. Meta-analysis of atrial fibrillation patient transcriptomes showed high correlation to the in vitro model. Treatment of the coculture with glucocorticoids showed reversal of phenotypes, including reduced beat irregularity, improved conduction, and reversed RNA expression profiles. CONCLUSIONS: This study establishes a causal relationship between M1 activation and the development of subsequent atrial arrhythmia, documented as irregularity in spontaneous electrical activation in atrial cardiomyocytes cocultured with activated macrophages. Further, beat rate irregularity could be alleviated using glucocorticoids. Overall, these results point at macrophage-mediated inflammation as a potential AF induction mechanism and offer new targets for therapeutic development. The findings strongly support the relevance of the proposed hiPSC-derived coculture model and present it as a first of its kind disease model.
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Fibrilación Atrial , Técnicas de Cocultivo , Células Madre Pluripotentes Inducidas , Macrófagos , Miocitos Cardíacos , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Miocitos Cardíacos/metabolismo , Fibrilación Atrial/metabolismo , Fibrilación Atrial/patología , Macrófagos/metabolismo , Fenotipo , Diferenciación Celular , Atrios Cardíacos/patología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/citologíaRESUMEN
AIMS: Atrial fibrosis and autonomic remodelling are proposed pathophysiological mechanisms in atrial fibrillation (AF). Their impact on conduction velocity (CV) dynamics and wavefront propagation was evaluated. METHODS AND RESULTS: Local activation times (LATs), voltage, and geometry data were obtained from patients undergoing ablation for persistent AF. LATs were obtained at three pacing intervals (PIs) in sinus rhythm (SR). LATs were used to determine CV dynamics and their relationship to local voltage amplitude. The impact of autonomic modulation- pharmacologically and with ganglionated plexi (GP) stimulation, on CV dynamics, wavefront propagation, and pivot points (change in wavefront propagation of ≥90°) was determined in SR. Fifty-four patients were included. Voltage impacted CV dynamics whereby at non-low voltage zones (LVZs) (≥0.5â mV) the CV restitution curves are steeper [0.03 ± 0.03â m/s ΔCV PI 600-400â ms (PI1), 0.54 ± 0.09â m/s ΔCV PI 400-250â ms (PI2)], broader at LVZ (0.2-0.49â mV) (0.17 ± 0.09â m/s ΔCV PI1, 0.25 ± 0.11â m/s ΔCV PI2), and flat at very LVZ (<0.2â mV) (0.03 ± 0.01â m/s ΔCV PI1, 0.04 ± 0.02â m/s ΔCV PI2). Atropine did not change CV dynamics, while isoprenaline and GP stimulation resulted in greater CV slowing with rate. Isoprenaline (2.7 ± 1.1 increase/patient) and GP stimulation (2.8 ± 1.3 increase/patient) promoted CV heterogeneity, i.e. rate-dependent CV (RDCV) slowing sites. Most pivot points co-located to RDCV slowing sites (80.2%). Isoprenaline (1.3 ± 1.1 pivot increase/patient) and GP stimulation (1.5 ± 1.1 increase/patient) also enhanced the number of pivot points identified. CONCLUSION: Atrial CV dynamics is affected by fibrosis burden and influenced by autonomic modulation which enhances CV heterogeneity and distribution of pivot points. This study provides further insight into the impact of autonomic remodelling in AF.
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Fibrilación Atrial , Fibrosis , Atrios Cardíacos , Humanos , Femenino , Masculino , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Persona de Mediana Edad , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/inervación , Anciano , Potenciales de Acción , Ablación por Catéter , Remodelación Atrial , Frecuencia Cardíaca , Técnicas Electrofisiológicas Cardíacas , Sistema Nervioso Autónomo/fisiopatología , Función del Atrio Izquierdo , Isoproterenol/farmacología , Atropina/farmacología , Factores de Tiempo , Sistema de Conducción Cardíaco/fisiopatología , Resultado del TratamientoAsunto(s)
Fibrilación Atrial , Ablación por Catéter , Embolia Aérea , Fístula Esofágica , Oxigenoterapia Hiperbárica , Embolia Intracraneal , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/terapia , Embolia Aérea/etiología , Embolia Aérea/terapia , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Fístula Esofágica/etiología , Oxigenoterapia Hiperbárica/métodos , Embolia Intracraneal/etiología , Masculino , Atrios Cardíacos/diagnóstico por imagen , Fístula/etiología , Persona de Mediana EdadRESUMEN
Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here we investigated how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in patients with AF. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell T cell receptor (TCR) sequencing identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, and the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signaling pathways. This study identified EAT as a reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.
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Tejido Adiposo , Fibrilación Atrial , Células T de Memoria , Pericardio , Fibrilación Atrial/inmunología , Fibrilación Atrial/genética , Fibrilación Atrial/patología , Fibrilación Atrial/metabolismo , Humanos , Pericardio/metabolismo , Pericardio/patología , Pericardio/inmunología , Tejido Adiposo/metabolismo , Tejido Adiposo/inmunología , Tejido Adiposo/patología , Células T de Memoria/inmunología , Células T de Memoria/metabolismo , Masculino , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Transcriptoma , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/inmunología , Femenino , Persona de Mediana Edad , Perfilación de la Expresión Génica , Anciano , Fenotipo , Señalización del Calcio , Apoptosis , Memoria Inmunológica , Transcripción Genética , Estudios de Casos y Controles , Atrios Cardíacos/patología , Atrios Cardíacos/inmunología , Atrios Cardíacos/metabolismo , Fibrosis/patología , Tejido Adiposo EpicárdicoRESUMEN
OBJECTIVES: The purpose of this study was to demonstrate the discriminating predictive indicators in peripheral blood and left atrium blood for predicting the risk of left atrial spontaneous echo contrast (LASEC) in atrial fibrillation patients underwent catheter ablation. METHODS: A total of 108 consecutive AF patients treated with radiofrequency ablation between July 2022 and July 2023 were enrolled and divided into two groups based on preprocedural transesophageal echocardiography: the non LASEC group (n = 71) and the LASEC group (n = 37). Circulating platelet and endothelial- derived MPs (PMPs and EMPs) in peripheral blood and left atrial blood were detected. Plasma soluble P-selectin (sP-selectin) and von Willebrand factor (vWF) were observed. Diagnostic efficiency was measured using receiver operating characteristic (ROC) curve. RESULTS: Peripheral sP-selectin, vWF and EMPs expressions elevated in all subjects when compared to those in left atrium blood. Levels of sP-selectin and vWF were significantly higher in peripheral blood of LASEC group than those of non LASEC group (p = 0.0018,p = 0.0271). Significant accumulations of peripheral PMPs and EMPs were documented in LASEC group by comparison with non LASEC group (p = 0.0395,p = 0.018). The area under curve(AUC) of combined PMPs and sP-selectin in predicting LASEC was 0.769 (95%CI: 0.678-0.845, sensitivity: 86.49%, specificity: 59.15%), significantly larger than PMPs or sP-selectin alone. CONCLUSIONS: Expressions of PMPs, sP-selectin, EMPs and vWF Increased in NVAF patients with LASEC and that might be potential biomarkers for LASEC prediction.
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Fibrilación Atrial , Biomarcadores , Ablación por Catéter , Ecocardiografía Transesofágica , Atrios Cardíacos , Selectina-P , Valor Predictivo de las Pruebas , Factor de von Willebrand , Humanos , Fibrilación Atrial/sangre , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/cirugía , Masculino , Femenino , Persona de Mediana Edad , Atrios Cardíacos/diagnóstico por imagen , Selectina-P/sangre , Factor de von Willebrand/metabolismo , Factor de von Willebrand/análisis , Biomarcadores/sangre , Anciano , Resultado del Tratamiento , Función del Atrio Izquierdo , Factores de Riesgo , Medición de RiesgoRESUMEN
Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm2, while maximal and minimal LA size from gated measurements were 19.6 cm2 and 11.9 cm2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = - 0.03, p = 0.006; ß = - 0.03, p = 0.021; ß = - 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT.
Asunto(s)
Atrios Cardíacos , Imagen por Resonancia Magnética , Pruebas de Función Respiratoria , Humanos , Femenino , Masculino , Persona de Mediana Edad , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Imagen por Resonancia Magnética/métodos , Anciano , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Mediciones del Volumen Pulmonar , Función del Atrio Izquierdo/fisiologíaRESUMEN
Conventional diastolic dysfunction parameters seem to be imperfect when applied to the pediatric cardiomyopathy population. The aim of this pilot study was to search for novel echocardiographic parameters associated with adverse outcomes in children with the most common cardiomyopathies. Fifty-six patients with pediatric cardiomyopathies (28 with dilated, 21 with hypertrophic, 7 with left ventricular non-compaction cardiomyopathy) and 28 healthy subjects were included in the study. Left atrial reservoir (LASr), conduit (LAScd) and contraction (LASct) strain, left atrial stiffness index (LASI), as well as conventional diastolic dysfunction parameters were measured using echocardiography. Adverse outcomes were defined as heart failure (including heart transplant) and arrhythmic endpoints. Patients with adverse outcomes presented with significantly lower LASr (16.68% ± 8.64% vs. 33.97% ± 9.99%, p-value < 0.001), lower LAScd (- 10.37% ± 5.83% vs. - 25.50% ± 9.24%, p-value < 0.001) and higher values of LASI (0.69 [IQR 0.34; 1.11] vs. 0.21 [IQR 0.16; 0.31], p-value < 0.001). LASr < 20%, LAScd ≥ - 12%, and LASI ≥ 0.26 were all associated with reduced survival. LASr, LAScd and LASI seem to be promising parameters in predicting adverse outcomes in the most common pediatric cardiomyopathies. Left atrial strain parameters and LASI are helpful in differentiating healthy control subjects from children with hypertrophic and dilated cardiomyopathies.
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Cardiomiopatías , Ecocardiografía , Atrios Cardíacos , Humanos , Masculino , Femenino , Proyectos Piloto , Niño , Cardiomiopatías/fisiopatología , Cardiomiopatías/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/diagnóstico por imagen , Preescolar , Adolescente , Función del Atrio Izquierdo/fisiologíaRESUMEN
BACKGROUND: Doxorubicin is an important anticancer drug, however, elicits dose-dependently cardiomyopathy. Given its mode of action, i.e. topoisomerase inhibition and DNA damage, we investigated genetic events associated with cardiomyopathy and searched for mechanism-based possibilities to alleviate cardiotoxicity. We treated rats at clinically relevant doses of doxorubicin. Histopathology and transmission electron microscopy (TEM) defined cardiac lesions, and transcriptomics unveiled cardiomyopathy-associated gene regulations. Genomic-footprints revealed critical components of Abl1-p53-signaling, and EMSA-assays evidenced Abl1 DNA-binding activity. Gene reporter assays confirmed Abl1 activity on p53-targets while immunohistochemistry/immunofluorescence microscopy demonstrated Abl1, p53&p73 signaling. RESULTS: Doxorubicin treatment caused dose-dependently toxic cardiomyopathy, and TEM evidenced damaged mitochondria and myofibrillar disarray. Surviving cardiomyocytes repressed Parkin-1 and Bnip3-mediated mitophagy, stimulated dynamin-1-like dependent mitochondrial fission and induced anti-apoptotic Bag1 signaling. Thus, we observed induced mitochondrial biogenesis. Transcriptomics discovered heterogeneity in cellular responses with minimal overlap between treatments, and the data are highly suggestive for distinct cardiomyocyte (sub)populations which differed in their resilience and reparative capacity. Genome-wide footprints revealed Abl1 and p53 enriched binding sites in doxorubicin-regulated genes, and we confirmed Abl1 DNA-binding activity in EMSA-assays. Extraordinarily, Abl1 signaling differed in the heart with highly significant regulations of Abl1, p53 and p73 in atrial cardiomyocytes. Conversely, in ventricular cardiomyocytes, Abl1 solely-modulated p53-signaling that was BAX transcription-independent. Gene reporter assays established Abl1 cofactor activity for the p53-reporter PG13-luc, and ectopic Abl1 expression stimulated p53-mediated apoptosis. CONCLUSIONS: The tyrosine kinase Abl1 is of critical importance in doxorubicin induced cardiomyopathy, and we propose its inhibition as means to diminish risk of cardiotoxicity.
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Cardiomiopatías , Doxorrubicina , Miocitos Cardíacos , Proteínas Proto-Oncogénicas c-abl , Transducción de Señal , Proteína p53 Supresora de Tumor , Animales , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteína p53 Supresora de Tumor/metabolismo , Transducción de Señal/efectos de los fármacos , Cardiomiopatías/inducido químicamente , Cardiomiopatías/patología , Cardiomiopatías/metabolismo , Proteínas Proto-Oncogénicas c-abl/metabolismo , Proteínas Proto-Oncogénicas c-abl/genética , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/efectos de los fármacos , Atrios Cardíacos/patología , Atrios Cardíacos/efectos de los fármacos , Atrios Cardíacos/metabolismo , Muerte Celular/efectos de los fármacos , Masculino , Ratas , Ratas WistarRESUMEN
INTRODUÇÃO Os mixomas são tumores primários cardíacos correspondendo em sua grande maioria de natureza benigna e de constituição sólida, sendo a prevalência mais comum no lado esquerdo (75 a 80% dos casos), com predomínio no sexo feminino. Apesar da histogênese mais comum ser benigna deve-se prosseguir com exérese precoce devido às possíveis complicações, em especial morte súbita e acidentes vasculares. O ecocardiograma é o exame diagnóstico de escolha pois caracteriza tamanho, localização e mobilidade da tumoração assim como a capacidade de obstrução e/ou de formação de êmbolos. Outra opção é a ressonância magnética cardíaca pois além das características anatômicas nos fornece dados de características do microambiente do tumor. DESCRIÇÃO DO CASO Paciente do sexo feminino, 40 anos, proveniente de São Paulo (SP). Deu entrada neste Serviço referenciada de hospital secundário com história de palpitações em precórdio associada a dispneia e astenia intensa com duração de 20 minutos há cerca de 3 meses. Nega queixas durante o período interepisódio assim como nega dor torácica. Como antecedentes patológicos possui fibrilação atrial (FA) paroxística com controle de frequência cardíaca com propranolol 40mg/dia e hipertensão arterial sistêmica (HAS) em uso de losartana 50mg/dia. Nega internações prévios devido o quadro supracitado. Em ECOTT realizado no serviço de origem presença de imagem hiperecoica, homogênea, aderida ao septo interatrial em átrio esquerdo medindo em seus maiores diâmetros aproximadamente 2,6x2,2cm sugestiva de mixoma atrial esquerdo. Prosseguindo investigação realizou novo ECOTT no Instituto Dante Pazzanese de Cardiologia (IDPC) onde observou-se imagem sugestiva de linha de dissecção que se inicia logo após a emergência da artéria subclávia esquerda que se estende até a aorta abdominal proximal. Atualmente recebendo propranolol 40mg/dia e losartana 50mg/dia, evoluindo com bons controles pressóricos e frequência cardíaca sendo programado a exérese de mixoma localizado em atrial esquerdo pela equipe do miocárdio do IDPC e posterior acompanhamento no ambulatório da equipe. CONCLUSÃO Apesar de se tratar de tumores raros e possuírem histologia benigna, os mixomas devem ser investigados e prosseguir com ressecção tumoral com brevidade, devido aos riscos de embolização. Idealmente a investigação deve ser iniciada com o ecocardiograma, seja o transesofágico ou transtorácico, como foi no caso relatado acima onde flagrou-se o mixoma em átrio esquerdo.
Asunto(s)
Humanos , Femenino , Adulto , Atrios Cardíacos , Mixoma , Fibrilación Atrial , Dolor en el Pecho , Espectroscopía de Resonancia Magnética , Muerte Súbita , Disección , DisneaRESUMEN
RATIONALE: Approximately one-fifth ischemic stroke are attributed to cardioembolism. Patients with cardioembolic stroke often develop a more severe disability and a higher risk of stroke recurrence. Cardiac myxoma, although uncommon, can serve as a potentially curable cause of acute embolic strokes. PATIENT CONCERNS: A 55-year-old male patient presented to the emergency department with acute vertigo and unsteady gait, accompanied by left upper limb numbness. Concurrently, purple-like lesions on the left hand were noticed. DIAGNOSES: Brain magnetic resonance imaging showed multiple infarctions in the posterior circulation. Additionally, skin examination showed Janeway lesions, Osler nodes and splinter hemorrhages. There was no evidence of systemic infection. Subsequently, transthoracic echocardiogram revealed a left atrial myxoma. INTERVENTION: Early surgical resection of cardiac myxoma was performed. OUTCOMES: The patient recovered well from the surgery. No recurrent embolic event was reported at 3-month postoperatively. LESSONS: Clinicians should be vigilant for skin manifestations of cardiac embolism. In patients with acute ischemic strokes, the presence of cutaneous embolic phenomena could serve as a warning sign of cardioembolism.
Asunto(s)
Atrios Cardíacos , Neoplasias Cardíacas , Accidente Cerebrovascular Isquémico , Mixoma , Humanos , Masculino , Mixoma/complicaciones , Mixoma/diagnóstico , Mixoma/cirugía , Persona de Mediana Edad , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirugía , Accidente Cerebrovascular Isquémico/etiología , Atrios Cardíacos/diagnóstico por imagen , Endocarditis/complicaciones , Endocarditis/diagnóstico , EcocardiografíaRESUMEN
Accurate segmentation of the left atrium (LA) from late gadolinium-enhanced cardiac magnetic resonance (LGE CMR) images is crucial for aiding the treatment of patients with atrial fibrillation. Few-shot learning holds significant potential for achieving accurate LA segmentation with low demand on high-cost labeled LGE CMR data and fast generalization across different centers. However, accurate LA segmentation with few-shot learning is a challenging task due to the low-intensity contrast between the LA and other neighboring organs in LGE CMR images. To address this issue, we propose an Adaptive Dynamic Inference Network (ADINet) that explicitly models the differences between the foreground and background. Specifically, ADINet leverages dynamic collaborative inference (DCI) and dynamic reverse inference (DRI) to adaptively allocate semantic-aware and spatial-specific convolution weights and indication information. These allocations are conditioned on the support foreground and background knowledge, utilizing pixel-wise correlations, for different spatial positions of query images. The convolution weights adapt to different visual patterns based on spatial positions, enabling effective encoding of differences between foreground and background regions. Meanwhile, the indication information adapts to the background visual pattern to reversely decode foreground LA regions, leveraging their spatial complementarity. To promote the learning of ADINet, we propose hierarchical supervision, which enforces spatial consistency and differences between the background and foreground regions through pixel-wise semantic supervision and pixel-pixel correlation supervision. We demonstrated the performance of ADINet on three LGE CMR datasets from different centers. Compared to state-of-the-art methods with ten available samples, ADINet yielded better segmentation performance in terms of four metrics.
Asunto(s)
Atrios Cardíacos , Humanos , Atrios Cardíacos/diagnóstico por imagen , Fibrilación Atrial/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Algoritmos , Medios de Contraste , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
BACKGROUND: Unknown cardioembolic sources are frequent causes of cryptogenic stroke. We analyzed the risk of atrial fibrillation (AF) or high burden of ectopic atrial activity (HBEA) in patients with cryptogenic stroke, assessing atrial function and 1-year outcomes. METHODS AND RESULTS: The ARIES (Atrial Imaging and Cardiac Rhythm in Cryptogenic Embolic Stroke) study is an observational study including patients with cryptogenic stroke. We analyzed the frequency of AF and HBEA (>3000 atrial ectopic beats/day or >2 bursts or atrial tachycardia between 3 beats and ≤30 seconds) in two 30-day Holter-ECGs, comparing advanced echocardiography signs of left atrial (LA) dysfunction according to rhythm: AF, HBEA, and normal sinus rhythm. We also evaluated 1-year stroke recurrence and mortality. The study included 109 patients; 35 (32.1%) patients had AF, 27 (24.8%) HBEA, and 47 (43.1%) normal sinus rhythm. Compared with those with normal sinus rhythm, patients with AF presented higher 2-dimensional and 3-dimensional LA indexed volumes (38.8±11.2 versus 27.3±11.8 mL/m2, and 50.6±17.2 versus 34.0±15.4 mL/m2, respectively, P<0.001), lower 3-dimensional LA ejection fraction (50±14.6 versus 62.7±11.8, P=0.001), LA reservoir strain (22.0±8.6 versus 30.4±10.5, P<0.001), and LA contraction strain (10.5±8.18 versus 17.1±7.5, P<0.001), remaining significant in multivariate analysis. Patients with HBEA showed higher LA indexed volumes and lower LA reservoir strain than patients with normal sinus rhythm only in univariate analysis. There were no differences in ischemic recurrence or mortality among the groups. CONCLUSIONS: Patients with cryptogenic stroke showed a high incidence of AF and HBEA. AF is strongly related to LA volume, LA function, and LA reservoir and contraction strain, whereas HBEA showed milder structural changes. Advanced LA echocardiography could help patient selection for long-term ECG monitoring in suspected cardiac sources.
Asunto(s)
Fibrilación Atrial , Función del Atrio Izquierdo , Electrocardiografía Ambulatoria , Accidente Cerebrovascular Embólico , Recurrencia , Humanos , Masculino , Femenino , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/complicaciones , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/diagnóstico , Anciano , Persona de Mediana Edad , Accidente Cerebrovascular Embólico/etiología , Accidente Cerebrovascular Embólico/fisiopatología , Función del Atrio Izquierdo/fisiología , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca/fisiología , Factores de Riesgo , Complejos Atriales Prematuros/fisiopatología , Complejos Atriales Prematuros/diagnóstico , Complejos Atriales Prematuros/complicaciones , Complejos Atriales Prematuros/epidemiología , Ecocardiografía/métodos , Factores de Tiempo , Medición de Riesgo/métodosRESUMEN
BACKGROUND: Left atrial (LA) fibrosis is a marker of atrial cardiomyopathy and has been reported to be associated with both atrial fibrillation and ischemic stroke. Elucidating this relationship is clinically important as LA fibrosis could serve as a surrogate biomarker of LA cardiomyopathy. The objective of this study is to investigate the association of LA fibrosis and embolic stroke of undetermined source (ESUS) using cardiac magnetic resonance imaging. METHODS AND RESULTS: Following an International Prospective Register of Systematic Reviews-registered protocol, 3 blinded reviewers performed a systematic review for studies that quantified the degree of LA fibrosis in patients with ESUS as compared with healthy patients from inception to February 2024. A meta-analysis was conducted in the mean difference. From 7 studies (705 patients), there was a significantly higher degree of LA fibrosis in patients with ESUS compared with healthy controls (MD, 5.71% [95% CI, 3.55%-7.87%], P<0.01). The degree of LA fibrosis was significantly higher in patients with atrial fibrillation than healthy controls (MD, 8.22% [95% CI, 5.62%-10.83%], P<0.01). A similar degree of LA fibrosis was observed in patients with ESUS compared with patients with atrial fibrillation (MD, -0.92% [95% CI, -2.29% to 0.44%], P=0.35). CONCLUSIONS: A significantly higher degree of LA fibrosis was found in patients with ESUS as compared with healthy controls. This suggests that LA fibrosis may play a significant role in the pathogenesis of ESUS. Further research is warranted to investigate LA fibrosis as a surrogate biomarker of atrial cardiomyopathy and recurrent stroke risk in patients with ESUS.