RESUMEN
BACKGROUND: Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined. METHODS: We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-HiChIP on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes. RESULTS: We identified 134 066 and 97 506 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs. CONCLUSIONS: We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.
Asunto(s)
Histonas , Miocitos Cardíacos , Humanos , Miocitos Cardíacos/metabolismo , Histonas/genética , Histonas/metabolismo , Estudio de Asociación del Genoma Completo , Lisina/genética , Lisina/metabolismo , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Cromatina/genética , Cromatina/metabolismo , Elementos de Facilitación Genéticos/genética , EstrógenosRESUMEN
Background: The impact of dominant ventricular morphology on Fontan patient outcomes remain controversial. This study evaluates long-term results of right ventricle (RV) dominance versus left ventricle (LV) dominance in Fontan circulation without hypoplastic left heart syndrome (HLHS). Methods: We retrospectively examined 323 Fontan operations from our center. To minimize pre- and intra-Fontan heterogeneity, 42 dominant RV patients were matched with 42 dominant LV patients using propensity score matching, allowing for a comparative analysis of outcomes between groups. Results: The mean follow-up was 8.0 ± 4.6 years for matched RV dominant and 6.5 ± 4.7 years for matched LV dominant group (p > 0.05), showing no significant difference. The cumulative incidence of moderate or greater atrioventricular valve regurgitation was also comparable between the two groups (p > 0.05). Similarly, 10-year freedom from death or transplantation following the Fontan operation was 84% ± 7% in the matched dominant RV group, similar to 81% ± 7% in the matched dominant LV group (p > 0.05). The 10-year freedom from Fontan failure was 78% ± 8% in the matched dominant RV group, also similar to 75% ± 8% in the matched dominant LV group (p > 0.05). Multivariate analysis did not identify RV dominance as a risk factor for Fontan failure (p > 0.05). Conclusions: In the pre- and intra-Fontan context, RV dominance demonstrated similar and comparable long-term outcomes compared to LV dominance in non-HLHS Fontan circulation.
RESUMEN
Background: Both systemic-to-pulmonary shunt and right ventricle-pulmonary artery (RV-PA) connection are extensively applied to initially rehabilitate the pulmonary artery in pulmonary atresia with the ventricle septal defect (PA/VSD). However, which of these options is the most ideal for promoting pulmonary artery development and improving outcomes remains controversial. Methods: A total of 109 PA/VSD patients undergoing initial rehabilitative surgery at Guangdong Provincial People's Hospital from 2010 to 2020 were enrolled in this study. A series of clinical data were collected to compare the perioperative and postoperative outcomes between systemic-to-pulmonary and RV-PA connection. Results: The mean duration of follow-up was 61.1 months in the systemic-to-pulmonary shunt group and 70.3 months in the RV-PA connection group (p > 0.05). The RV-PA connection technique resulted in a significantly higher PaO 2 , lower red blood cells (RBC), lower hemoglobin, and lower hematocrit (Hct) (p < 0.05). The cumulative incidence curve estimated a cumulative complete repair rate of 56 ± 7% after 5 years in the RV-PA connection group, significantly higher than 36 ± 7% after 5 years in the systemic-to-pulmonary shunt group (p < 0.05). The Kaplan-Meier curve revealed a similar estimated survival rate between the two groups (p = 0.73). The RV-PA connection was identified as an independent predictor for complete repair in the multivariable analysis (HR = 2.348, 95% CI = 1.131-4.873). Conclusions: The RV-PA connection is a more ideal initial rehabilitative technique than systemic-to-pulmonary shunt in treating PA/VSD as a consequence of comparable probability of survival but improved definitive complete repair rate.
RESUMEN
KEY MESSAGE: KT1 was validated as a novel thickness QTL with major effects on wheat kernel dimensions and weight and fine mapped to a 0.04 cM interval near the chromosome-5A centromere. Kernel size, the principal grain weight determining factor of wheat and a target trait for both domestication and artificial breeding, is mainly defined by kernel length (KL), kernel width (KW) and kernel thickness (KT), of which KW and KT have been shown to be positively related to grain weight (GW). Qkt.nau-5A, a major QTL for KT, was validated using the QTL near-isogenic lines (NILs) in three genetic backgrounds. Genetic analysis using two F2 populations derived from the NILs showed that Qkt.nau-5A was dominant for thicker kernel and inherited like a single gene and therefore was designated as Kernel Thickness 1 (KT1). With 77 recombinant lines identified from a total of 19,160 F2 plants from the two NIL-derived F2 populations, KT1 was mapped to the 0.04 cM Xwgrb1356-Xwgrb1619 interval, which was near the centromere and displayed strong recombination suppression. The KT1 interval showed positive correlation with KW and GW and negative correlation with KL and therefore could be used in breeding for cultivars with round-shaped kernels that are beneficial to higher flour yield. KT1 candidate identification could be achieved through combination of sequence variation analysis with expression profiling of the annotated genes in the interval.
Asunto(s)
Cromosomas de las Plantas , Triticum , Mapeo Cromosómico/métodos , Cromosomas de las Plantas/genética , Grano Comestible/genética , Fenotipo , Fitomejoramiento , Sitios de Carácter Cuantitativo , Semillas/genética , Triticum/genéticaRESUMEN
BACKGROUND: The transaortic Morrow procedure is the current gold standard for hypertrophic obstructive cardiomyopathy (HOCM) patients who are resistant to maximum drug therapy. It is controversial whether concomitant mitral valve intervention is necessary. Only a few centers apply for concomitant anterior mitral leaflet extension with a bovine or autologous pericardial patch to further decrease systolic anterior motion. Our aim is to assess the primeval outcomes of thoracoscopic transmitral myectomy with anterior mitral leaflet extension (TTM-AMLE) in symptomatic HOCM patients. METHODS: Between April 2019 and November 2020, 18 consecutive HOCM patients who underwent TTM-AMLE were enrolled in this study. Preoperative, postoperative, and follow-up outcomes were compared and statistically analyzed. RESULTS: The mean age was (50.17 ± 6.18) years and 10 (55.56%) were males. 18 (100%) patients had mitral regurgitation preoperatively, and they all successfully underwent TTM-AMLE with a median cardiopulmonary bypass and aortic cross-clamp time of 200.0 (150.8, 232.0), and 127.5 (116.0, 149.0) min, respectively. The median length of ICU stay was 2.7 (1.4, 5.2) days. The interventricular septum thickness was significantly reduced (from 18.03 ± 3.02 mm to 11.91 ± 1.66 mm, p < .001). There was no perioperative mortality, perforation of ventricular septum, or conversion to sternotomy observed. During a median follow-up of 18 months (IQR, 5-24 months), 1 (5.56%) patient had severe mitral regurgitation due to patch detachment and received reoperation. Moderate degree of mitral regurgitation and more than 50 mmHg in left ventricular outflow tract gradient were found in 2 (11.11%), and 1 (5.56%) patients, respectively. 1 (5.56%) patient who had second-degree atrioventricular block received permanent pacemaker implantation postoperatively. Overall, the maximum left ventricular outflow tract gradient (88.50 [59.50, 112.75] mmHg vs. 10.50 [7.00, 15.50] mmHg, p = .002), left ventricular outflow tract velocity (4.70 [3.86, 5.33] m/s vs. 1.60 [1.33, 1.95] m/s, p < .001) and the degree of mitral regurgitation (6.99 ± 4.47 cm2 vs. 2.22 ± 1.51 cm2 , p = .001) were significantly decreased, with a significant reduction in the proportion of systolic anterior motion (94.44% vs. 16.67%, p < .001). CONCLUSIONS: The TTM-AMLE is a safe and effective surgical approach for selected patients with HOCM. In our series, it provides excellent relief of left ventricular outflow tract obstruction, while significantly eliminating mitral regurgitation. The early outcomes of TTM-AMLE are satisfactory, but further studies and longer follow-ups are awaited.
Asunto(s)
Cardiomiopatía Hipertrófica , Insuficiencia de la Válvula Mitral , Tabique Interventricular , Adulto , Animales , Cardiomiopatía Hipertrófica/complicaciones , Bovinos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/complicaciones , Resultado del Tratamiento , Tabique Interventricular/cirugíaRESUMEN
Extensive and serious mitral annular calcification represents a troublesome obstacle in intracardiac mitral valve replacement due to time-consuming requirements and the potential of decalcification-associated complications. We report the case of a high-risk patient with extremely severe mitral insufficiency and difficult-to-debride annular calcification who received mitral replacement using a chimney technique. This approach enabled not only the minimization of mitral calcification debridement but also the reduction of surgery time. Consequently, the surgery was successful with a great postoperative outcome. Thus, this technique is a safe and feasible option to deal with intractable mitral annular calcification during mitral valve surgery.
Asunto(s)
Calcinosis , Cardiopatías Congénitas , Enfermedades de las Válvulas Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Humanos , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Enfermedades de las Válvulas Cardíacas/cirugía , Calcinosis/cirugía , Cardiopatías Congénitas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Resultado del TratamientoRESUMEN
Wnt/ß-catenin signaling plays a key role in pathological cardiac remodeling in adults. The identification of a tissue-specific Wnt/ß-catenin interaction factor may provide a tissue-specific clinical targeting strategy. Drosophila Pygo encodes the core interaction factor of Wnt/ß-catenin. Two Pygo homologs (Pygo1 and Pygo2) have been identified in mammals. Different from the ubiquitous expression profile of Pygo2, Pygo1 is enriched in cardiac tissue. However, the role of Pygo1 in mammalian cardiac disease is yet to be elucidated. In this study, we found that Pygo1 was upregulated in human cardiac tissues with pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy accompanied by declined cardiac function, increased heart weight/body weight and heart weight/tibial length ratios, and increased cell size. The canonical ß-catenin/T-cell transcription factor 4 (TCF4) complex was abundant in Pygo1-overexpressing transgenic (Pygo1-TG) cardiac tissue, and the downstream genes of Wnt signaling, that is, Axin2, Ephb3, and c-Myc, were upregulated. A tail vein injection of ß-catenin inhibitor effectively rescued the phenotype of cardiac failure and pathological myocardial remodeling in Pygo1-TG mice. Furthermore, in vivo downregulated pygo1 during cardiac hypertrophic condition antagonized agonist-induced cardiac hypertrophy. Therefore, our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for tissue-specific clinical treatment via targeting this pathway.NEW & NOTEWORTHY In this study, we found that Pygo1 is associated with human pathological hypertrophy. Cardiac-specific overexpression of Pygo1 in mice spontaneously led to cardiac hypertrophy. Meanwhile, cardiac function was improved when expression of Pygo1 was interfered in hypertrophy-model mice. Our study is the first to present in vivo evidence demonstrating that Pygo1 regulates pathological cardiac hypertrophy in a canonical Wnt/ß-catenin-dependent manner, which may provide new clues for a tissue-specific clinical treatment targeting this pathway.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Insuficiencia Cardíaca/metabolismo , Hipertrofia Ventricular Izquierda/metabolismo , Miocardio/metabolismo , Función Ventricular Izquierda , Remodelación Ventricular , Vía de Señalización Wnt , beta Catenina/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Proteína Axina/genética , Proteína Axina/metabolismo , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/prevención & control , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/patología , Isoproterenol , Masculino , Ratones Transgénicos , Miocardio/patología , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Ratas , Receptor EphB3/genética , Receptor EphB3/metabolismo , Tiazolidinas/farmacología , Factor de Transcripción 4/genética , Factor de Transcripción 4/metabolismo , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To identify left ventricular (LV) myocardial mechanics predictors of LV outflow tract obstruction (LVOTO) in patients with hypertrophic cardiomyopathy (HCM). METHODS: Thirty-nine adults with HCM and 21 controls underwent cardiovascular magnetic resonance. The feature tracking (FT) analysis results of HCM patients with and without LVOTO and controls were compared. RESULTS: Global radial strain measured on the short-axis slice (GRS-SAX) (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.15; P < 0.01), global longitudinal strain measured on the long-axis slice (GLS-LAX) (OR, 1.81; 95% CI, 1.21-2.73; P < 0.01) and GRS measured on the long-axis slice (GRS-LAX) (OR, 1.07; 95% CI, 1.01-1.13; P = 0.02) were independent predictors of LVOTO. The combination of GRS-SAX plus GLS-LAX and GRS-LAX showed great discriminatory power for identifying LVOTO with an area under the receiver operating characteristic curve value of 0.91 (95% CI: 0.81-1.00). CONCLUSIONS: In adult HCM patients, GRS-SAX, GLS-LAX, and GRS-LAX were independent predictors of LVOTO. The combination of GRS-SAX plus GLS-LAX and GRS-LAX showed great discriminatory power for identifying LVOTO.
Asunto(s)
Cardiomiopatía Hipertrófica/patología , Ventrículos Cardíacos/patología , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Adolescente , Adulto , Cateterismo Cardíaco , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Curva ROC , Adulto JovenRESUMEN
BACKGROUND: Single-stage unifocalisation for pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCA) requires a high degree of three-dimensional (3D) anatomical imagination. A previous study has reported the application of a 3D-printed heart model with virtual reality (VR) or mixed reality (MR). However, few studies have evaluated the surgical outcomes of the 3D model with VR or MR in PA/VSD patients. METHODS: Three-dimensional (3D) heart models of five selected PA/VSD patients were derived from traditional imageology of their hearts. Using VR glasses, the 3D models were also visualised in the operating room. Both the 3D-printed heart models and preoperative evaluation by VR were used in the five selected patients for surgical simulation and better anatomical understanding. Mixed reality holograms were used as perioperative assistive tools. Surgical outcomes were assessed, including in-hospital and early follow-up clinical data. RESULTS: The use of these three new technologies had favourable feedback from the surgeons on intraoperative judgment. There were no in-hospital or early deaths. No reintervention was required until the last follow-up. Three (3) patients developed postoperative complications: one had right bundle branch block and ST-segment change, one had chest drainage >7 days (>40 mL/day) and one had pneumonia. CONCLUSION: The preoperative application of a 3D-printed heart model with VR or MR helped in aligning the surgical field. These technologies improved the understanding of complicated cardiac anatomy and achieved acceptable surgical outcomes as guiding surgical planning.
Asunto(s)
Realidad Aumentada , Procedimientos Quirúrgicos Cardíacos/métodos , Impresión Tridimensional , Arteria Pulmonar/cirugía , Atresia Pulmonar/cirugía , Preescolar , Angiografía por Tomografía Computarizada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Arteria Pulmonar/diagnóstico por imagen , Atresia Pulmonar/diagnóstico , Estudios RetrospectivosRESUMEN
Pygo is a nuclear protein containing two conserved domains, NHD and PHD, which play important roles in embryonic development and carcinogenesis. Pygo was first identified as a core component of the Wnt/ß-catenin signalling pathway. However, it has also been reported that the function of Pygo is not always Wnt/ß-catenin signalling dependent. In this review, we summarise the functions of both domains of Pygo and show that their functions are synergetic. The PHD domain mainly combines with transcription co-factors, including histone 3 and Bcl9/9l. The NHD domain mainly recruits histone methyltransferase/acetyltransferase (HMT/HAT) to modify lysine 4 of the histone 3 tail (H3K4) and interacts with Chip/LIM-domain DNA-binding proteins (ChiLS) to form enhanceosomes to regulate transcriptional activity. Furthermore, we summarised chromatin modification differences of Pygo in Drosophila (dPygo) and vertebrates, and found that Pygo displayes a chromatin silencing function in Drosophila, while in vertebates, Pygo has a chromatin-activating function due to the two substitution of two amino acid residues. Next, we confirmed the relationship between Pygo and Bcl9/9l and found that Pygo-Bcl/9l are specifically partnered both in the nucleus and in the cytoplasm. Finally, we discuss whether transcriptional activity of Pygo is Wnt/ß-catenin dependent during embryonic development. Available information indications that the transcriptional activity of Pygo in embryonic development is either Wnt/ß-catenin dependent or independent in both tissue-specific and cell-specific-modes.
Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Wnt/metabolismo , Vía de Señalización Wnt , Animales , Proteínas de Drosophila/química , Proteínas de Drosophila/fisiología , Drosophila melanogaster/embriología , Silenciador del Gen/fisiología , Histona Acetiltransferasas/metabolismo , Histona Metiltransferasas/metabolismo , Péptidos y Proteínas de Señalización Intracelular/química , Péptidos y Proteínas de Señalización Intracelular/fisiología , Conformación Proteica , Dominios Proteicos , beta Catenina/metabolismoRESUMEN
OBJECTIVES: This study aimed to develop non-invasive machine learning classifiers for predicting post-Glenn shunt patients with low and high risks of a mean pulmonary arterial pressure (mPAP) > 15 mmHg based on preoperative cardiac computed tomography (CT). METHODS: This retrospective study included 96 patients with functional single ventricle who underwent a bidirectional Glenn procedure between November 1, 2009, and July, 31, 2017. All patients underwent post-procedure CT, followed by cardiac catheterization. Overall, 23 morphologic parameters were manually extracted from cardiac CT images for each patient. The Mann-Whitney U or chi-square test was applied to select the most significant predictors. Six machine learning algorithms including logistic regression, Naive Bayes, random forest (RF), linear discriminant analysis, support vector machine, and K-nearest neighbor were used for modeling. These algorithms were independently trained on 100 train-validation random splits with a 3:1 ratio. Their average performance was evaluated by area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Seven CT morphologic parameters were selected for modeling. RF obtained the best performance, with mean AUC of 0.840 (confidence interval [CI] 0.832-0.850) and 0.787 (95% CI 0.780-0.794); sensitivity of 0.815 (95% CI 0.797-0.833) and 0.778 (95% CI 0.767-0.788), specificity of 0.766 (95% CI 0.748-0.785) and 0.746 (95% CI 0.735-0.757); and accuracy of 0.782 (95% CI 0.771-0.793) and 0.756 (95% CI 0.748-0.764) in the training and validation cohorts, respectively. CONCLUSIONS: The CT-based RF model demonstrates a good performance in the prediction of mPAP, which may reduce the need for right heart catheterization in post-Glenn shunt patients with suspected mPAP > 15 mmHg. KEY POINTS: ⢠Twenty-three candidate descriptors were manually extracted from cardiac computed tomography images, and seven of them were selected for subsequent modeling. ⢠The random forest model presents the best predictive performance for pulmonary pressure among all methods. ⢠The computed tomography-based machine learning model could predict post-Glenn shunt pulmonary pressure non-invasively.
Asunto(s)
Presión Sanguínea , Procedimiento de Fontan , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/cirugía , Arteria Pulmonar/diagnóstico por imagen , Máquina de Vectores de Soporte , Adolescente , Algoritmos , Teorema de Bayes , Cateterismo Cardíaco , Niño , Preescolar , Análisis Discriminante , Ventrículo Derecho con Doble Salida/diagnóstico por imagen , Ventrículo Derecho con Doble Salida/cirugía , Femenino , Defectos de los Tabiques Cardíacos/diagnóstico por imagen , Defectos de los Tabiques Cardíacos/cirugía , Humanos , Lactante , Modelos Logísticos , Pulmón , Aprendizaje Automático , Masculino , Pronóstico , Atresia Pulmonar/diagnóstico por imagen , Atresia Pulmonar/cirugía , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Transposición de los Grandes Vasos/diagnóstico por imagen , Transposición de los Grandes Vasos/cirugía , Atresia Tricúspide/diagnóstico por imagen , Atresia Tricúspide/cirugía , Corazón Univentricular/diagnóstico por imagen , Corazón Univentricular/cirugía , Adulto JovenRESUMEN
IMPORTANCE: A high prevalence of retinal abnormalities have been reported in congenital heart disease (CHD), but quantitative analysis of retinal vasculature is scarce. Optical coherence tomography angiography (OCTA) is a noninvasive method to quantitatively assess the retinal microvasculature. BACKGROUND: To investigate the retinal microvasculature changes in CHD patients by using OCTA. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 158 participants including 57 cyanotic CHD (CCHD) patients, 60 acyanotic CHD (ACHD) patients and 41 control subjects were included. METHODS: All participants underwent a comprehensive ophthalmologic examination, including refraction measurement, intraocular pressure measurement and OCTA. MAIN OUTCOME MEASURES: Vessel density (VD) was measured within the radial peripapillary capillary (RPC), superficial capillary plexus (SCP) and deep capillary plexus (DCP) of the macula. RESULTS: CCHD patients had significantly lower VD in the RPC, SCP and DCP (all P < .01) compared to control subjects, and significantly lower VD in the RPC and DCP (both P < .05) compared to ACHD patients. Besides, among the CHD group, VD in the RPC was positively correlated with oxygen saturation (whole image, ρ = 0.45; peripapillary, ρ = 0.48) and negatively correlated with haematocrit (whole image, ρ = 0.55; peripapillary, ρ = 0.55) (all P < .001). CONCLUSIONS AND RELEVANCE: Retinal VD might be a surrogate to reflect the effect of chronic systemic hypoxemia in CHD patients. OCTA could be a convenient and noninvasive tool to evaluate the retinal structure and function in CHD patients.
Asunto(s)
Cardiopatías Congénitas , Tomografía de Coherencia Óptica , Estudios Transversales , Angiografía con Fluoresceína , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Humanos , MicrovasosRESUMEN
Normal high density lipoprotein (HDL) protects vascular function; however these protective effects of HDL may absent in valvular heart disease (VHD). Because vascular function plays an important role in maintaining the circulation post-cardiac surgery and some patients are difficult to stabilize, we hypothesized that a deleterious vascular effect of HDL may contribute to vascular dysfunction in VHD patients following surgery. HDL was isolated from age-match 28 healthy subjects and 84 patients with VHD and during cardiac surgery. HDL pro-inflammation index was measured and the effects of HDL on vasodilation, protein interaction, generation of nitric oxide (NO) and superoxide were determined. Patients with VHD received either simvastatin (20mg/d) or routine medications, and endothelial effects of HDL were characterized. HDL inflammation index significantly increased in VHD patients and post-cardiac surgery. HDL from VHD patients and post-cardiac surgery significantly impaired endothelium-dependent vasodilation, inhibited both Akt and endothelial nitric oxide synthase (eNOS) phosphorylation at S1177, eNOS associated with heat shock protein 90 (HSP90), NO production and increased eNOS phosphorylation at T495 and superoxide generation. Simvastatin therapy partially reduced HDL inflammation index, improved the capacity of HDL to stimulate eNOS and Akt phosphorylation at S1177, eNOS associated with HSP90, NO production, reduced eNOS phosphorylation at T495 and superoxide generation, and improved endothelium-dependent vasodilation. Our data demonstrated that HDL from VHD patients and cardiac surgery contributed to endothelial dysfunction through uncoupling of eNOS. This deleterious effect can be reversed by simvastatin, which improves the vasoprotective effects of HDL. Targeting HDL may be a therapeutic strategy for maintaining vascular function and improving the outcomes post-cardiac surgery.
Asunto(s)
Enfermedades de las Válvulas Cardíacas/metabolismo , Válvulas Cardíacas/metabolismo , Lipoproteínas HDL/metabolismo , Adulto , Anciano , Animales , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/patología , Estudios de Casos y Controles , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/patología , Femenino , Regulación de la Expresión Génica , Proteínas HSP90 de Choque Térmico/genética , Proteínas HSP90 de Choque Térmico/metabolismo , Enfermedades de las Válvulas Cardíacas/tratamiento farmacológico , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/patología , Válvulas Cardíacas/efectos de los fármacos , Válvulas Cardíacas/patología , Humanos , Hipolipemiantes/uso terapéutico , Lipoproteínas HDL/farmacología , Masculino , Ratones , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Simvastatina/uso terapéutico , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismo , Vasodilatación/efectos de los fármacosRESUMEN
Mitral valve endothelial cells are important for maintaining lifelong mitral valve integrity and function. Plasma endothelial microparticles (EMPs) increased in various pathological conditions related to activation of endothelial cells. However, whether EMPs will increase in mitral valve disease and their relationship remains unclear. Here, 81 patients with mitral valve disease and 45 healthy subjects were analyzed for the generation of EMPs by flow cytometry. Human mitral valve endothelial cells (HMVECs) were treated with EMPs. The phosphorylation of Akt and endothelial nitric oxide synthase (eNOS), the association of eNOS and heat shock protein 90 (HSP90), and the generation of nitric oxide (NO) and superoxide anion (O(2)(â-)) were measured. EMPs were increased significantly in patients with mitral valve disease compared with those in healthy subjects. EMPs were negatively correlated with mitral valve area in patients with isolated mitral stenosis. EMPs were significantly higher in the group with severe mitral regurgitation than those in the group with mild and moderate mitral regurgitation. Furthermore, EMPs were decreased dramatically in both Akt and eNOS phosphorylation and the association of HSP90 with eNOS in HMVECs. EMPs decreased NO production but increased O(2)(â-) generation in HMVECs. Our data demonstrated that EMPs were significantly increased in patients with mitral valve disease. The increase of EMPs can in turn impair HMVEC function by inhibiting the Akt/eNOS-HSP90 signaling pathway. These findings suggest that EMPs may be a therapeutic target for mitral valve disease.
Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Células Endoteliales , Insuficiencia de la Válvula Mitral/metabolismo , Estenosis de la Válvula Mitral/metabolismo , Válvula Mitral , Óxido Nítrico Sintasa de Tipo III/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Adulto , Estudios de Casos y Controles , Células Cultivadas , Células Endoteliales/citología , Células Endoteliales/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Proteínas HSP90 de Choque Térmico/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/citología , Válvula Mitral/metabolismo , Óxido Nítrico/metabolismo , Fosforilación , Transducción de Señal , Superóxidos/metabolismoRESUMEN
Mouse models of myocardial ischemic preconditioning (IPC) and ischemic postconditioning (IPD) have proven to be very useful models of cardiovascular diseases. In 2010, Gao described a novel procedure without the aid of mechanical ventilation. However, the technique of heart externalization could not be applied to mouse models of IPC or IPD due to the limited time frame of the technique. We proposed a modified simple and safe method using lung recruitment and short-term ventilation to perform the procedure in mice with IPC or IPD. The mice were randomly divided into 4 groups: the modified groups, M-IPC and M-IPD, and the conventional groups, C-IPC and C-IPD. In the 2 modified groups, the mice were removed from the ventilator and allowed to resume breathing spontaneously upon completion of the lung recruitment and the rapid closure of the thorax. Our study demonstrated that the postoperative recovery time was significantly reduced for the modified groups compared with the 2 conventional groups. Moreover, the inflammatory damages were attenuated by the modified method compared with the conventional method. In addition, the modified method significantly increased the survival rates of mice with IPC or IPD. The modified method improved the survival rates of mouse models of myocardial ischemia.
Asunto(s)
Modelos Animales de Enfermedad , Poscondicionamiento Isquémico/métodos , Precondicionamiento Isquémico Miocárdico/métodos , Isquemia Miocárdica/terapia , Animales , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/etiología , Vasos Coronarios , Incidencia , Interleucina-6/sangre , Ligadura , Masculino , Ratones , Ratones Endogámicos C57BL , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/patología , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: Transaortic myectomy is a common procedure for patients with hypertrophic obstructive cardiomyopathy. Thoracoscopic trans-mitral myectomy has been described in a few small-sample studies and has been recommended as preferable. We herein report our clinical outcomes using the thoracoscopic trans-mitral approach with 76 patients. METHODS: This is a retrospective single-centre analysis of the safety and efficacy of thoracoscopic trans-mitral myectomy by comparing the clinical outcomes with that of transaortic myectomy. RESULTS: Between April 2019 and October 2021, 132 patients underwent either a transaortic (n = 56) or a thoracoscopic trans-mitral myectomy (n = 76). Compared with those in the transaortic group, patients in the trans-mitral group were more likely to be weaned off the ventilator within 24 h after surgery (80.3% vs 60.7%, P < 0.05) and to require a shorter duration of ventilation [29.01 (43.91) vs 51.12 (94.96) h, P = 0.08] and lower transfusion rate (26.3% vs 48.2%, P < 0.05). The in-hospital mortality rate of the transaortic and trans-mitral groups was 3.6% (n = 2) and 1.3% (n = 1), respectively. No significant inter-group differences were observed regarding in-hospital mortality, the incidence of low cardiac output syndrome or permanent pacemaker implantations. In the trans-mitral group, the thickness of the interventricular septum was significantly reduced postoperatively, with resultant relief of the left ventricular outflow tract obstruction [89.37 (27.5) vs 10.51 (0.65) mmHg, P < 0.01]. Transaortic myectomy also resulted in a significant reduction in left ventricular outflow tract gradient [90.41 (33.31) vs 11.35 (9.43) mmHg, P < 0.01]. And the incidence of residual systolic anterior motion of the trans-mitral group and the transaortic group was 2.67% and 1.9%, respectively. CONCLUSIONS: The thoracoscopic trans-mitral approach provides excellent exposure to the septum and anomalies of the mitral valve and papillary muscle. It relieves obstruction effectively, without increasing the incidence of major complications.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Cardiomiopatía Hipertrófica , Insuficiencia de la Válvula Mitral , Tabique Interventricular , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/métodos , Tabique Interventricular/cirugía , Cardiomiopatía Hipertrófica/complicaciones , Insuficiencia de la Válvula Mitral/cirugíaRESUMEN
Congenital heart disease (CHD) is one of the leading causes of mortality among birth defects, and due to significant variations in the whole heart and great vessel, automatic CHD segmentation using CT images has been always under-researched. Even though some segmentation algorithms have been developed in the literature, none perform very well under the complex structure of CHD. To deal with the challenges, we take advantage of deep learning in processing regular structures and graph algorithms in dealing with large variations and propose a framework combining both the whole heart and great vessel segmentation in complex CHD. We benefit from deep learning in segmenting the four chambers and myocardium based on the blood pool, and then we extract the connection information and apply graph matching to determine the categories of all the vessels. Experimental results on 68 3D CT images covering 14 types of CHD illustrate our framework can increase the Dice score by 12% on average compared with the state-of-the-art whole heart and great vessel segmentation method in normal anatomy. We further introduce two cardiovascular imaging specialists to evaluate our results in the standard of the Van Praagh classification system, and achieves well performance in clinical evaluation. All these results may pave the way for the clinical use of our method in the incoming future.
Asunto(s)
Cardiopatías Congénitas , Humanos , Cardiopatías Congénitas/diagnóstico por imagen , Redes Neurales de la Computación , Miocardio , Algoritmos , VíscerasRESUMEN
BACKGROUND: Microcirculatory dysfunction is associated with increased morbidity and mortality in cardiac surgery patients. This study aimed to investigate the association between preoperative retinal microcirculation evaluated using optical coherence tomography angiography (OCTA) and perioperative outcomes in patients with congenital heart disease (CHD). METHODS: This prospective, observational study was performed from May 2017 to January 2021. OCTA was used to automatically quantify the vessel density (VD) of the superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary (RPC) preoperatively. The primary outcome was excessive postoperative bleeding, defined as bleeding volume > 75th percentile for 24-hour postoperative chest tube output. The secondary outcome was composite adverse outcomes, including one or more operative mortalities, early postoperative complications, and prolonged length of stay. The association between retinal VD and outcomes was assessed using Poisson regression. RESULTS: In total, 173 CHD patients who underwent cardiac surgery were included (mean age, 26 years). Among them, 43 (24.9%) and 46 (26.6%) developed excessive postoperative bleeding and composite adverse outcomes, respectively. A lower VD of DCP (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.08-1.43; P = 0.003) was independently associated with excessive postoperative bleeding, and a lower VD of RPC (OR, 1.97; 95% CI, 1.08-3.57; P = 0.027), and DCP (OR, 2.17; 95% CI, 1.08-4.37; P = 0.029) were independently associated with the postoperative composite adverse outcomes. CONCLUSION: Preoperative retinal hypoperfusion was independently associated with an increased risk of perioperative adverse outcomes in patients with CHD, suggesting that retinal microcirculation evaluation could provide valuable information about the outcomes of cardiac surgery, thereby aiding physicians in tailoring individualized treatment.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Retina , Humanos , Adulto , Angiografía con Fluoresceína/métodos , Microcirculación , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodosRESUMEN
OBJECTIVES: To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). METHODS: The clinical data of children with CHD aged 0-14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. RESULTS: A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0-14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. CONCLUSIONS: The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD.
Asunto(s)
Cardiopatías Congénitas , Masculino , Lactante , Humanos , Estudios Retrospectivos , Cardiopatías Congénitas/cirugía , Tiempo de Internación , Hospitales , ToracotomíaRESUMEN
Background: There is a lack of evidence guiding the surgical timing selection in pulmonary atresia with ventricular septal defect. This study aims to compare the long-term outcomes of different initial rehabilitative surgical ages in patients with pulmonary atresia with ventricular septal defect (PAVSD). Methods: From January 2011 to December 2020, a total of 101 PAVSD patients undergoing the initial rehabilitative surgery at our center were retrospectively reviewed. Receiver-operator characteristics curve analysis was used to identify the cutoff age of 6.4 months and therefore to classify the patients into two groups. Competing risk models were used to identify risk factors associated with complete repair. The probability of survival and complete repair were compared between the two groups using the Kaplan-Meier curve and cumulative incidence curve, respectively. Results: The median duration of follow-up was 72.76 months. There were similar ΔMcGoon ratio and ΔNakata index between the two groups. Multivariate analysis showed that age ≤6.4 months (hazard ratio (HR) = 2.728; 95% confidence interval (CI):1.122-6.637; p = 0.027) and right ventricle-to-pulmonary artery connection (HR = 4.196; 95% CI = 1.782-9.883; p = 0.001) were associated with increased probability of complete repair. The cumulative incidence curve showed that the estimated complete repair rates were 64% ± 8% after 3 years and 69% ± 8%% after 5 years in the younger group, significantly higher than 28% ± 6% after 3 years and 33% ± 6% after 5 years in the elder group (p < 0.001). There was no significant difference regarding the estimated survival rate between the two groups. Conclusion: Compared with those undergoing the initial rehabilitative surgery at the age >6.4 months, PAVSD patients at the age ≤6.4 months had an equal pulmonary vasculature development, a similar probability of survival but an improved probability of complete repair.