Genetic analysis of a Chinese pedigree affected with Mucopolysaccharidosis type ⅢA / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A).@*METHODS@#A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site.@*RESULTS@#The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range.@*CONCLUSION@#The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.

Relationship of Microvascular Obstruction with Global and Regional Myocardial Function Determined by Cardiac Magnetic Resonance after ST-Segment Elevation Myocardial Infarction / 中国医学科学杂志(英文版)

Objective To investigate the impact of microvascular obstruction (MVO) on the global and regional myocardial function by cardiac magnetic resonance feature-tracking (CMR-FT) in ST-segment-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention.Methods Consecutive acute STEMI patients who underwent cardiac magnetic resonance imaging 1 - 7 days after successful reperfusion by percutaneous coronary intervention treatment were included in this retrospective study. Based on the presence or absence of MVO on late gadolinium enhancement images, patients were divided into groups with MVO and without MVO. The infarct zone, adjacent zone, and remote zone were determined based on a myocardial 16-segment model. The radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle (LV) and the infarct, adjacent, and remote zones were measured by CMR-FT from cine images and compared between patients with and without MVO using independent-samples t-test. Logistic regression analysis was used to assess the association of MVO with the impaired LV function.Results A total of 157 STEMI patients (mean age 56.66 ± 11.38 years) were enrolled. MVO was detected in 37.58% (59/157) of STEMI patients, and the mean size of MVO was 3.00 ±3.76 mL. Compared with patients without MVO (n =98 ), the MVO group had significantly reduced LV global RS (t= -4.30, P < 0.001), global CS (t= 4.99, P < 0.001), and global LS ( t= 3.51, P = 0.001). The RS and CS of the infarct zone in patients with MVO were significantly reduced (t= -3.38, P = 0.001; t= 2.64, P = 0.01; respectively) and the infarct size was significantly larger (t= 8.37, P < 0.001) than that of patients without MVO. The presence of LV MVO [OR= 4.10, 95%CI: 2.05 - 8.19, P<0.001) and its size [OR=1.38, 95%CI: 1.10-1.72, P=0.01], along with the heart rate and LV infarct size were significantly associated with impaired LV global CS in univariable Logistic regression analysis, while only heart rate (OR=1.08, 95%CI: 1.03 - 1.13, P=0.001) and LV infarct size (OR=1.10, 95%CI: 1.03 - 1.16, P=0.003) were independent influencing factors for the impaired LV global CS in multivariable Logistic regression analysis.Conclusion The infarct size was larger in STEMI patients with MVO, and MVO deteriorates the global and regional LV myocardial function.

The value of cardiac MRI in the risk stratification in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0<LGE%<5%, 5%≤LGE%<15% and LGE%≥15% groups. There were significant survival differences between these 4 groups whether for primary endpoint or secondary endpoint (all P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.

Mecânica Atrial na Cardiomiopatia Hipertrófica: Discriminando Hipertrofia de Fibrose Ventricular / Atrial Mechanics in Hypertrophic Cardiomyopathy: Discriminating between Ventricular Hypertrophy and Fibrosis

Resumo Fundamento A cardiomiopatia hipertrófica (CMH) e a hipertrofia ventricular esquerda (HVE) secundária à hipertensão arterial sistêmica (HAS) podem estar associadas a anormalidades funcionais do átrio esquerdo (AE). Objetivos Caracterizar a mecânica do AE na CMH e na HAS e avaliar qualquer correlação com a extensão da fibrose ventricular esquerda medida por ressonância magnética cardíaca (RMC) em pacientes com CMH. Métodos A função longitudinal do AE derivada do ecocardiograma bidimensional com speckle tracking foi adquirida a partir de cortes apicais de 60 pacientes com CMH e 34 indivíduos controles, pareados por idade. Pacientes com CMH também foram submetidos à RMC, com medida da extensão do realce tardio por gadolínio. A associação com parâmetros de strain do AE foi analisada. Valores p < 0,05 foram definidos como estatisticamente significativos. Resultados A média da fração de ejeção do ventrículo esquerdo não foi diferente entre os grupos. A razão E/e' estava comprometida no grupo CMH e preservada no grupo controle. A mecânica do AE estava significativamente reduzida na CMH em comparação aos pacientes com HAS. O strain rate do AE nas fases de reservatório (SRrAE) e na fase contrátil (SRctAE) foram os melhores parâmetros de discriminação de CMH com uma área sob a curva (AUC) de 0,8, seguido do strain do AE na fase de reservatório (SrAE) (AUC 0,76). O SRrAE e o SRctAE apresentaram elevada especificidade (89% e 91%, respectivamente), e o SrAE apresentou sensibilidade de 80%. Um decréscimo de 2,79% no strain rate do AE na fase de condução (SRcdAE) foi preditor de um aumento de 1 cm na extensão do RT pelo gadolínio (r2=0,42, β 2,79, p=0,027). Conclusões O SRrAE e o SRctAE foram os melhores fatores de discriminação de HVE secundária à CMH. O SRcdAE foi preditor do grau de fibrose ventricular esquerda avaliada por RMC. Esses achados sugerem que a mecânica do AE pode ser um potencial preditor de gravidade de doença na CMH.

Abstract Background Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Associations of Infarct Size and Regional Myocardial Function Examined by Cardiac Magnetic Resonance Feature Tracking Strain Analysis with the Infarct Location in Patients with Acute ST-Segment Elevation Myocardial Infarction / 中国医学科学杂志(英文版)

Objective To quantitatively evaluate the associations of infarct size, regional myocardial function examined by cardiac magnetic resonance feature tracking (CMR-FT) strain analysis with infarct location in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention.Methods Cardiac magnetic resonance images were retrospectively analyzed in 95 consecutive STEMI patients with successful reperfusion. The patients were divided into the anterior wall myocardial infarction (AWMI) and nonanterior wall myocardial infarction (NAWMI) groups. Infarct characteristics were assessed by late gadolinium enhancement. Global and regional strains and associated strain rates in the radial, circumferential and longitudinal directions were assessed by CMR-FT based on standard cine images. The associations of infarct size, regional myocardial function examined by CMR-FT strain analysis with infarct location in STEMI patients were evaluated by the Spearman or Pearsonmethod. Results There were 44 patients in the AWMI group and 51 in the NAWMI group. The extent of left ventricular enhanced mass was significantly larger in patients with AWMI compared with the NAWMI group (24.47±11.89, 21.06±12.08 %LV; t=3.928, P = 0.008). In infarct zone analysis, strains in the radial, circumferential and longitudinal directions were remarkably declined in the AWMI group compared with the NAWMI group (z=-20.873, -20.918, -10.357, all P < 0.001). The volume (end-systolic volume index), total enhanced mass and extent of enhanced mass of the left ventricular were correlated best with infarct zone strain in the AWMI group (all P < 0.001). Conclusion In STEMI patients treated by percutaneous coronary intervention, myocardial damage is more extensive and regional myocardial function in the infarct zone is lower in the AWMI group compared with the NAWMI group.

Hipoacusia sensorineural asimétrica en el diagnóstico de schwannoma vestibular / Asymmetric sensorineural hearing loss in the diagnosis of vestibular schwannoma

Introducción: se ha descrito que los pacientes con hipoacusia asimétrica cursan en un 2% con lesiones retrococleares. La conducta de escrutinio se ha basado en la audiometría. Existen varias definiciones de asimetría audiométrica descritas en la literatura, pero sin llegar a un consenso. Aunque la prueba de oro para el diagnóstico de schwannoma vestibular es la resonancia magnética con gadolíneo, la sospecha clínica se hace en base a la asimetría audiométrica. Objetivo: hacemos una revisión de los trabajos publicados al respecto en la literatu-ra y comentamos nuestra experiencia. Reflexión: queremos enfatizar en la importancia de estudiar a los pacientes con hipoacusia asimétrica con el fin de descartar patología retrococlear. Conclusión: a pesar de que no existe un consenso claro en la definición de hi-poacusia asimétrica, la sospecha clínica de un schwannoma vestibular se basa en la audiometría

Background: It is described that 2% of patients with asymmetric hearing loss have retrocochlear lesions. The scrutiny behavior has been based on audiometry. There are several definitions of audiometric asymmetry described in the literature, but without reaching a consensus. Although the gold standard for the diagnosis of vestibular schwannoma is gadolinium magnetic resonance imaging, the clinical sus-picion is based on audiometric asymmetry. Objective: we review the results published in this regard in the literature and com-ment on our own experience. Reflection: we want to emphasize the importance of studying asymmetric hearing loss patients in order to rule out retrocochlear etiology. Conclusions: although there is no clear consensus on the definition of asym-metric hearing loss, the clinical suspicion of a vestibular schwannoma is based on the audiometry.

Dedicated sellar magnetic resonance imaging protocols without contrast enhancement in girls with central precocious puberty: prevalence of pathologic lesions and clinical correlation

ABSTRACT Objective: Contrast-enhanced brain magnetic resonance imaging (MRI) is routinely performed in children with central precocious puberty (CPP). We evaluated the value of a dedicated sellar MRI protocol without contrast enhancement in girls with CPP. Subjects and methods: This study included 261 girls diagnosed with CPP. We performed sellar MRI scanning without gadolinium enhancement of the hypothalamic-pituitary area (HPA) at the pituitary level, including additional T2-weighted imaging of whole-brain scans to check for other lesions. We evaluated the prevalence of intracranial lesions via this MR protocol. In addition,the correlation between the clinical parameters and morphology of the pituitary gland on the images was assessed. Results: Intracranial lesions were detected in 17 (6.5%) of the 261 girls. Of the 17 girls with abnormalities, 16 (94.1%) had findings in brain areas other than the HPA. The weight, height, Tanner stage of patients were significantly (p < 0.05) higher in the group with greater pituitary height. Patient weight and height, Tanner stage of breast development, and luteinizing hormone (LH) levels were significantly (p < 0.05) greater in those with a higher pituitary grade as determined on sellar MRI. Conclusion: A dedicated unenhanced sellar MRI protocol provides valuable information on brain lesions and pituitary morphology. We found a significantly low prevalence of brain lesions among girls with CPP. Analysis of the height or shape of the pituitary gland on sellar MRI revealed significant correlations with the weight, height, Tanner stage, and LH levels of the patients.

Análise de Custo-Efetividade da Terapia com Evolocumabe em Pacientes com Alto Risco de Eventos Cardiovasculares no Contexto do SUS - Brasil / Cost-Effectiveness Analysis of Evolocumab Therapy in Patients at High Risk of Cardiovascular Events in the Context of the Brazilian Unified Health System

Resumo Fundamento: Em associação às estatinas, os inibidores da pró-proteína convertase subtilisina/kexina tipo 9 (PCSK9) demonstraram ser eficazes na redução de eventos cardiovasculares em pacientes de alto risco. Objetivo: Analisar a custo-efetividade da implementação de evolocumabe para pacientes com alto risco de eventos cardiovasculares no contexto do Sistema Único de Saúde (SUS) no Brasil. Métodos: Um modelo de Markov foi utilizado, baseando-se em uma amostra ambulatorial de pacientes com doença arterial coronariana. Os desfechos primários analisados foram infarto agudo do miocárdio, acidente vascular cerebral isquêmico (AVCi), revascularização do miocárdio e morte cardiovascular. O resultado foi expresso por meio da razão de custo-efetividade incremental (RCEI), considerando-se uma taxa de desconto de 5% ao ano, e uma análise de sensibilidade foi realizada, tendo em vista a imprecisão de valores. Resultados: Selecionaram-se 61 pacientes com risco cardiovascular estimado em 35% em 10 anos, se em uso de atorvastatina 80mg/dia, e em 22,75%, se adicionado o evolocumabe. O custo global por paciente no período de 10 anos foi de R$ 46.522,44 no grupo em monoterapia com atorvastatina versus R$ 236.141,85 na terapia combinada, com uma efetividade global de 0,54 e 0,73, respectivamente. Isso resultou em uma RCEI R$ 1.011.188,07 (R$ 864.498,95 a R$ 1.296.748,43) por desfecho cardiovascular evitado. Conclusões: Apesar de não existirem padrões nacionais para custo-efetividade, os dados encontrados sugerem que a estratégia de associação do evolocumabe à terapia com estatina não é, no momento, custo-efetiva.

Abstract Background: Hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH) secondary to systemic hypertension (HTN) may be associated with left atrial (LA) functional abnormalities. Objectives: We aimed to characterize LA mechanics in HCM and HTN and determine any correlation with the extent of left ventricular (LV) fibrosis measured by cardiac magnetic resonance (CMR) in HCM patients. Methods: Two-dimensional speckle tracking-derived longitudinal LA function was acquired from apical views in 60 HCM patients, 60 HTN patients, and 34 age-matched controls. HCM patients also underwent CMR, with measurement of late gadolinium enhancement (LGE) extension. Association with LA strain parameters was analyzed. Statistical significance was set at p<0.05. Results: Mean LV ejection fraction was not different between the groups. The E/e' ratio was impaired in the HCM group and preserved in the control group. LA mechanics was significantly reduced in HCM, compared to the HTN group. LA strain rate in reservoir (LASRr) and in contractile (LASRct) phases were the best discriminators of HCM, with an area under the curve (AUC) of 0.8, followed by LA strain in reservoir phase (LASr) (AUC 0.76). LASRr and LASR-ct had high specificity (89% and 91%, respectively) and LASr had sensitivity of 80%. A decrease in 2.79% of LA strain rate in conduit phase (LASRcd) predicted an increase of 1cm in LGE extension (r2=0.42, β 2.79, p=0.027). Conclusions: LASRr and LASRct were the best discriminators for LVH secondary to HCM. LASRcd predicted the degree of LV fibrosis assessed by CMR. These findings suggest that LA mechanics is a potential predictor of disease severity in HCM.

Relação entre o Realce Tardio pelo Gadolínio e os Parâmetros de Repolarização Ventricular em Pacientes com Insuficiência Cardíaca com Fração de Ejeção Reduzida / Relationship between Late Gadolinium Enhancement and Ventricular Repolarization Parameters in Heart Failure Patients with Reduced Ejection Fraction

Resumo Fundamento A insuficiência cardíaca com fração de ejeção reduzida (ICFEr) é uma doença de alta prevalência que requer hospitalizações repetidas e causa morbimortalidade significativa. Portanto, o reconhecimento precoce de preditores de resultados desfavoráveis é essencial para o manejo do paciente. Objetivo O objetivo do presente estudo é investigar a relação entre realce tardio pelo gadolínio (RTG) detectado por ressonância magnética cardíaca (RMC) e os parâmetros de repolarização, como o intervalo QT corrigido (QTc), intervalo Tp-e, ângulo QRS-T frontal detectado pelo eletrocardiograma (ECG) de 12 derivações na ICFEr. Método Neste estudo observacional, retrospectivo, de centro único, foram incluídos 97 pacientes consecutivos com ICFEr submetidos à RMC. A população do estudo foi dividida em dois grupos, de acordo com a presença de RTG. Foram registradas medidas ecocardiográficas e de RMC e características demográficas. Os intervalos QTc, intervalos Tp-e, e ângulos QRS-T frontais foram calculados a partir do ECG. Um valor de p <0,05 foi considerado estatisticamente significativo. Resultados O RTG foi detectado em 52 (53,6%) de 97 pacientes com ICFEr. Os intervalos QTc (p=0,001), intervalos Tp-e (p<0,001), e os ângulos QRS-T frontais (p<0,001) foram significativamente maiores no grupo RTG quando comparados ao grupo não-RTG. Na análise de regressão univariada realizada para investigar os preditores de RTG na ICFEr, todos os três parâmetros de repolarização alcançaram valores significativos, mas na análise multivariada o único parâmetro de repolarização que permaneceu significativo foi o intervalo Tp-e (OR = 1,085 IC 95% 1,032-1,140, p=0,001). Conclusão Com o prolongamento do intervalo Tp-e, pode-se prever a presença de fibrose miocárdica, a qual é um substrato arritmogênico, em pacientes com ICFEr.

Abstract Background Heart failure with reduced ejection fraction (HFrEF) is a highly prevalent disease that requires repeating hospitalizations, causes significant morbidity and mortality. Therefore, early recognition of poor outcome predictors is essential for patient management. Objective The aim of the present study is to investigate the relationship between late gadolinium enhancement (LGE) detected by cardiac magnetic resonance (CMR) and repolarization parameters such as corrected QT (QTc) interval, Tp-e interval, frontal QRS-T angle detected by 12 lead electrocardiograph (ECG) in HFrEF. Method In this single-center, retrospective observational study included 97 consecutive HFrEF patients who had CMR scan. Study population was divided into two groups according to the presence of LGE. Echocardiographic and CMR measurements and demographic features were recorded. QTc intervals, Tp-e intervals, frontal QRS-T angles were calculated from the ECG. A p-value less than 0.05 was considered statistically significant. Results LGE was detected in 52 (53.6%) out of 97 HFrEF patients. QTc intervals (p=0.001), Tp-e intervals (p<0.001), frontal QRS-T angles (p<0.001) were found to be significantly higher in LGE group when compared to non-LGE group. In univariate regression analysis which was performed to investigate the predictors of LGE in HFrEF, all three repolarization parameters were reached significant values but in multivariate analysis the only repolarization parameter remained significant was Tp-e interval (OR=1.085 95% CI 1.032-1.140, p=0.001). Conclusion With the prolongation of the Tp-e interval, the presence of myocardial fibrosis which is an arrhythmogenic substrate, can be predicted in patients with HFrEF.

Fibrosis endomiocárdica: una cardiomiopatía restrictiva en países en vía de desarrollo / Endomyocardial fibrosis: a restrictive cardiomyopathy in developing countries

Resumen Objetivo: La fibrosis endomiocárdica (FE) es una cardiomiopatía restrictiva infrecuente. En América Latina son escasos los reportes. En el presente trabajo se realiza una descripción de una serie de pacientes diagnosticados de FE en Colombia. Método: Realizamos una búsqueda en los registros de imágenes de resonancia magnética (RM) cardiaca realizadas en nuestra institución entre 2016 y 2019 en busca de pacientes con diagnóstico de FE. Se describieron sus características sociodemográficas, clínicas y de imagen. Resultados: Nueve pacientes fueron diagnosticados de FE (el 66.7% mujeres), con una edad promedio de 69 años. Los pacientes presentaron un promedio de 2.6 años de evolución. El principal síntoma referido fue disnea, seguido de síncope, dolor torácico y palpitaciones. En ninguno de ellos se sospechó FE como diagnóstico inicial. En cuanto a los hallazgos ecocardiográficos, se identificó compromiso predominante del ventrículo izquierdo, seguido de compromiso biventricular. Todos los pacientes presentaron patrón de llenado restrictivo con dilatación auricular izquierda severa. En el análisis retrospectivo se cumplieron los criterios de Mocumbi para el diagnóstico de FE en el 100% de los pacientes con gravedad moderada (77.8%). Las imágenes de RM mostraron función sistólica biventricular y volúmenes preservados. Se observó depósito focal de gadolinio subendocárdico a nivel apical y se confirmó la presencia de trombo en el 66% de los casos Conclusión:: La FE es una cardiomiopatía restrictiva infrecuente circunscrita a países tropicales. La mayoría de los pacientes en nuestra serie presentaron compromiso aislado del ventrículo izquierdo, seguido de compromiso biventricular, con función ventricular usualmente preservada.

Abstract Objective: Endomyocardial fibrosis (EF) is an unusual restrictive cardiomyopathy. In Latin America there are few reports. Here, we made a description of patients diagnosed with EF in Colombia. Method: We conducted a search in the records of cardiac magnetic resonance imaging (MRI) performed in our institution between 2016-2019 looking for patients with a diagnosis of EF; sociodemographic, clinical and imaging characteristics were described. Results: Nine patients were diagnosed with EF (66.7% female), with an average age of 69 years. Patients presented an average evolution of 2.6 years. The main reported symptom was dyspnea, followed by syncope, chest pain, and palpitations. None of them was initially suspected for EF. Regarding echocardiographic findings, predominant left ventricular involvement was identified, followed by bi-ventricular involvement. All the patients presented a restrictive filling pattern with severe left atrial dilation. In a retrospective analysis, Mocumbi criteria for diagnosis of EF were met in 100% of the patients, majority with moderate severity (77.8%). Cardiac MRI showed biventricular systolic function and volumes preserved. Focal subendocardial late gadolinium enhancement was observed on the apex and apical thrombus was confirmed in 66% of the patients Conclusion: FE is an uncommon restrictive cardiomyopathy limited to tropical countries. Most of patients in our series presented isolated involvement of left ventricle, followed by bi-ventricular involvement, with ventricular function usually preserved.

Gadolinium angiography of inner ear in patients with sudden deafness and its clinical analysis / 中华耳鼻咽喉头颈外科杂志

Objective: To observe the gadolinium imaging findings of inner ear in patients with sudden deafness and to analyze its clinical features. Methods: From November 2017 to July 2020, 21 patients with sudden deafness in the People's Hospital of Dongsheng District, Ordos City were selected as the research objects, including 14 males and 7 females, aged 36-76 years, with a median age of 50 years. The course of disease was 1-19 days, with an average of 5.5 days. The patients received audiology tests, laboratory examination, and intravenous gadolinium angiography, each of whom was scanned twice by 3D-FLAIR sequence: once before intravenous gadolinium injection, and once again 4.5-6.0 h after intravenous gadolinium injection. The following corresponding clinical treatment was given. The imaging manifestations and clinical features were observed. Results: Among 21 cases of sudden deafness in acute stage, the signal intensity of 11 cases was significantly higher than that of the contralateral ear, and 2 cases had vestibular labyrinthine hydrops. In laboratory examination, only 2 cases of total deafness had increased WBC count and faster erythrocyte sedimentation rate, and the rest had no abnormality. The hearing types of 21 patients with sudden deafness were: total deafness in 8 cases, flat decline in 10 cases, low frequency decline in 1 case, high frequency decline in 2 cases. The total effective rate was 57% (12/21). The hearing types of 11 patients with abnormal gadolinium angiography were total deafness in 5 cases, flat decline in 5 cases and high frequency decline in 1 case. The total effective rate was 64% (7/11). Conclusion: Gadolinium angiography is abnormal in some patients with sudden deafness, and the permeability of blood labyrinth barrier may be increased, which is worthy of further study.

hsa-miR-4443 inhibits myocardial fibroblast proliferation by targeting THBS1 to regulate TGF-ß1/α-SMA/collagen signaling in atrial fibrillation

Fibrosis caused by the increase in extracellular matrix in cardiac fibroblasts plays an important role in the occurrence and development of atrial fibrillation (AF). The aim of this study was to investigate the role of hsa-miR-4443 in AF, human cardiac fibroblast (HCFB) proliferation, and extracellular matrix remodeling. TaqMan Stem-loop miRNA assay was used to measure hsa-miR-4443 expression in patients with persistent AF (n=123) and healthy controls (n=100). Patients with AF were confirmed to have atrial fibrosis by late gadolinium enhancement. At the cellular level, after hsa-miR-4443 mimic and inhibitor were transfected with HCFBs, proliferation, apoptosis, migration, and invasion were analyzed. Lastly, hsa-miR-4443-targeted gene and transforming growth factor (TGF)-β1/α-SMA/collagen pathway were evaluated by dual-luciferase reporter assay and western blot, respectively. In patients with AF, hsa-miR-4443 decreased significantly and collagen metabolism level increased significantly. Logistic regression analysis showed that low hsa-miR-4443 level was a risk factor of AF (P<0.001). The receiver operating characteristic curve revealed that hsa-miR-4443 was useful for predicting AF (area under the curve: 0.828, sensitivity: 0.71, specificity: 0.78, P<0.001). In HCFBs, hsa-miR-4443 targeted thrombospondin-1 (THBS1) and downregulated TGF-β1/α-SMA/collagen pathway. The inhibition of hsa-miR-4443 expression promoted HCFB proliferation, migration, invasion, myofibroblast differentiation, and collagen production. The significant reduction of hsa-miR-4443 can be used as a biomarker for AF. hsa-miR-4443 protected AF by targeting THBS1 and regulated TGF-β1/α-SMA/collagen pathway to inhibit HCFB proliferation and collagen synthesis.

Clinical value of left ventricular strain analysis by cardiovascular magnetic resonance in patients with coronary chronic total occlusion / 中华心血管病杂志

Objective: To explore the clinical value of quantitatively assessment of left ventricular strain in patients with coronary chronic total occlusion (CTO) by cardiac magnetic resonance imaging (CMR)-feature tracking (CMR-FT) technique. Methods: In this retrospective and observation study, patients with single CTO, who underwent CMR examination in Beijing Anzhen Hospital from November 2014 to January 2019, were selected as case group (CTO group), and those without cardiovascular diseases defined by echocardiography, electrocardiogram (ECG) and clinical history and with normal CMR results were selected as healthy control group (control group). General clinical data including age, gender, discharge diagnosis, and the examination results of echocardiography and ECG were obtained from the electronic medical record system. Two-dimensional CMR-FT was applied to measure left ventricle (LV) global peak radial, circumferential, and longitudinal strains (GPRS, GPCS and GPLS, respectively), and the regional myocardial strain in the target vessel area of CTO was analyzed. Grayscale thresholds of 5 standard deviations (SDs) were used to quantify late gadolinium enhancement (LGE). Patients with CTOs were divided into infract size>10% group and infarct size≤10% group, and left ventricular ejection fraction (LVEF)≥50% group and LVEF<50% group, respectively. The differences between various groups were compared. Results: There were 52 patients in CTO group (34 males, age (54.1±11.7) years, body mass index (BMI) (26.2±2.5)kg/m2) and 30 patients in control group (14 males, age(51.6±12.3)years, BMI (25.6±3.3)kg/m2). There was no significant difference in age, gender, and BMI between the two groups (all P>0.05). LVEF, GPRS, GPCS and GPLS were significantly lower in CTO group than in control group (all P<0.05), left ventricular volume (LVEDV) was similar between the two groups (P>0.05). Among the patients with CTO, there were 26 patients with infarct size>10% and 26 patients with infarct size≤10%. GPRS, GPCS and GPLS were significantly lower (all P<0.05), while LVEF and LVEDV were similar in CTO patients with infarct size≤10% as compared to control group (both P>0.05). LVEF, GPRS, GPCS and GPLS were significantly lower (all P<0.05), while LVEDV was similar in CTO patients with infarct size>10% (P>0.05) as compared to control group. GPRS and GPCS were significantly lower (both P<0.05), while LVEF, LVEDV and GPLS were similar in CTO patients with infarct size>10% as compared to infarct size≤10% group. There were 40 subjects in LVEF≥50% group and 12 subjects in LVEF<50% group. Compared with the control group, GPCS and GPLS of CTO patients were significantly lower in LVEF≥50% group and LVEF<50% group (all P<0.01), LVEF and LVEDV was similar in CTO patients with LVEF≥50% (both P>0.05), but LVEF was lower and LVEDV was larger in LVEF<50% group (both P<0.05). The GPRS, GPCS, GPLS and LVEF of CTO patients in LVEF ≥ 50% group were higher than those in LVEF<50% group (all P<0.0l), and the myocardial infarction size was smaller than that in LVEF reduced group (P<0.0l), but there was no significant difference in LVEDV between the two groups (P=0.07). In the CTO group, there were 21 patients with left anterior descending artery (LAD) occlusion and 126 segments supplied by the target vessels. The peak radial strain (PRS), circumferential strain (PCS) and longitudinal strain (PLS) in the blood supply area were lower than those in the control group (all P<0 01). In 7 patients with left circumflex artery (LCX) occlusion, the number of myocardial segments supplied by the target vessels was 35, and the PRS, PCS and PLS in the target vessel supply area were lower than those in the control group (all P<0 05). In 24 patients with right coronary artery (RCA) occlusion, the number of myocardial segments supplied by the target vessels was 120, and the PRS, PCS and PLS in the target vessel supply area were lower than those in the control group (all P<0.01). Among the 126 segments in 21 patients with LAD CTO, 91 (72.2%) segments had infarct size≤25%, 17 (13.5%) segments had infarct size between 26%-50%, 11 segments (8.7%) had infarct size between 51%-75%, and 7 (5.6%) segments had infarct size between 76%-100%. Among the 35 segments in 7 patients with LCX CTO, 31 (88.6%) segments had infarct size≤25%, and 4 (11.4%) segments had infarct size between 26%-75%. Among the 120 segments in 24 patients with RCA CTO, 96 (80.0%) segments had infarct size≤25%, 11 (9.2%) segments had infarct size between 26%-50%, 8 (6.7%) segments had infarct size between 51%-75%, and 5 segments (4.2%) had infarct size between 76%-100%. Conclusions: In this study with single CTO, although the LVEF is preserved in the majority of the patients, the left ventricular global and regional strain values are significantly decreased. The larger the infarct size, the greater the impact on radial and circumferential motion, reflecting the early impairment of left ventricular function in these patients.

Extent of Left Atrial Ablation Lesions and Atrial Fibrillation Recurrence after Catheter Ablation - A Systematic Review and Meta-Analysis / A Extensão das Lesões de Ablação no Átrio Esquerdo e a Recorrência de Fibrilação Atrial após Ablação por Cateter - Uma Revisão Sistemática e Metanálise

Abstract Background: Atrial fibrillation (AF) is known to induce atrial remodeling, which promotes fibrosis related to arrhythmogenesis. Accordingly, since scars induced by catheter ablation (CA) can reduce unablated fibrotic areas, greater extent of left atrial (LA) scarring may be associated with less AF recurrence after CA. Objectives: This study aims to investigate, through systematic review and meta-analysis, whether the amount of LA scarring, seen on late gadolinium enhancement magnetic resonance imaging, is associated with less AF recurrence after CA. Methods: The recommendations of the MOOSE guideline were followed. Database search was conducted in PubMed and Cochrane Central Register of Controlled Trials (comentário 1) until January 2019 (comentário 2). Two authors performed screening, data extraction, and quality evaluation. All studies were graded as good quality. A funnel plot was generated, showing no publication bias. Statistical significance was defined as p value < 0.05. Results: Eight observational studies were included in the systematic review, four of which were included in the meta-analysis. Six of the eight studies included in the systematic review showed that greater extension of LA scarring is associated with less AF recurrence after CA. Meta-analysis showed that greater extension of LA scarring is associated with less AF recurrence (SMD = 0.52; 95% CI 0.27 - 0.76; p < 0.0001). Conclusion: Greater extension of LA scarring is possibly associated with less AF recurrence after CA. Randomized studies that explore ablation methods based on this association are fundamental.

Resumo Fundamento: A fibrilação atrial (FA) é conhecida por induzir o remodelamento atrial, que promove fibrose, provocando, por sua vez, mais arritmogênese. Dessa forma, visto que as cicatrizes induzidas pela ablação por cateter (AC) podem reduzir as áreas fibróticas, uma maior extensão de cicatrizes do átrio esquerdo (AE) pode estar associada a uma menor recorrência da FA após AC. Objetivos: Por meio de revisão sistemática e metanálise, o presente estudo visa investigar se a extensão total de cicatriz do AE, visualizada na ressonância magnética com realce tardio de gadolínio após a ablação, está associada a uma menor recorrência de FA após AC. Métodos: Foram seguidas as recomendações das diretrizes MOOSE. A busca foi realizada nas bases de dados PubMed e Cochrane Central Register of Controlled Trials até Janeiro de 2019. Dois autores realizaram triagem, extração de dados e avaliação da qualidade dos estudos. Em relação à qualidade, todos os estudos foram classificados como bons. Foi gerado um gráfico de funil, o qual não mostrou viés de publicação. Foi adotado nível de significância p < 0,05. Resultados: Oito estudos observacionais foram incluídos na revisão sistemática, dos quais quatro foram incluídos na metanálise. Dos oito estudos incluídos na revisão, seis mostraram que maior extensão de cicatrização do AE está associada a uma menor recorrência de FA após AC. A metanálise também demonstrou que maior extensão de cicatrização do AE está associada a uma menor recorrência de FA (SMD = 0,52; IC 95% 0,27 - 0,76; p < 0,0001). Conclusão: Uma maior extensão de cicatrização do AE está possivelmente associada a uma menor recorrência de FA após AC. Estudos randomizados que explorem métodos de ablação baseados nessa associação são fundamentais.

Gadolinium-enhanced MRI reveals dynamic development of endolymphatic hydrops in Ménières disease / Ressonância magnética com gadolínio revela o desenvolvimento dinâmico da hidropsia endolinfática na doença de Ménière

Abstract Introduction: Meniere's disease is associated with impaired hearing, tinnitus, vertigo, and aural fullness. Many anatomical studies have suggested idiopathic endolymphatic hydrops as the pathological basis of Meniere's disease, which now can be visualized by using gadolinium -enhanced magnetic resonance imaging of the inner ear. Objective: To investigate the development of endolymphatic hydrops in Meniere's disease by monitoring the vestibules and cochleae of affected patients. Methods: Inner ears of 178 patients with definite unilateral Meniere's disease diagnosis were visualized by 3-dimensional fluid-attenuated inversion recovery and three-dimensional real inversion recovery magnetic resonance imaging following bilateral gadolinium intratympanic injection. The scans were used to evaluate the presence and degree of endolymphatic hydrops in the vestibules and cochlear structures, including the cochlear apical turn, the cochlear middle turn, and the cochlear basal turn. The correlation of endolymphatic hydrops occurrence between the various parts of the inner ear was determined. Results: Symptomatic endolymphatic hydrops was detected on the affected side in all patients, whereas asymptomatic endolymphatic hydrops was detected on the unaffected contra-lateral side in 32 patients (18.0%). On the affected side, the cochlear apical turn and the cochlear middle turn demonstrated significantly higher rates of endolymphatic hydrops than the cochlear basal turn and the vestibule. The severity of endolymphatic hydrops gradually decreased from the cochlear apical turn to the cochlear basal turn. On the contra lateral side, the incidence and degree of the detected asymptomatic endolymphatic hydrops were significantly greater in the cochleae than in the vestibules (p < 0.05), with no significant difference detected between the cochlear turns. Conclusion: Progression of endolymphatic hydrops appears to be directional, initiated in the cochlea. The order of endolymphatic hydrops severity gradually decreases from the cochlear apical turn to the cochlear basal turn and then to the vestibule. Endolymphatic hydrops in the vestibule is associated with symptomatic Meniere's disease.

Resumo Introdução: A doença de Ménière está associada a deficiência auditiva, zumbido, vertigem e plenitude auricular. Muitos estudos anatômicos sugerem hidropsia endolinfática idiopática como a base patológica da doença, que agora pode ser visualizada através de estudo por imagem da orelha interna por ressonância magnética com gadolínio. Objetivo: Investigar o desenvolvimento da hidropsia endolinfática na doença de Ménière com monitoramento dos vestíbulos e das cócleas dos pacientes afetados. Métodos: Orelhas internas de 178 pacientes com diagnóstico definitivo de doença de Ménière unilateral foram visualizados através de imagem de recuperação de inversão atenuada por fluidos em ressonância magnética tridimensional, 3-D FLAIR, e por inversão real após injeção intratimpânica bilateral de gadolínio. Os exames foram usados para avaliar a presença e o grau de hidropsia endolinfática nos vestíbulos e nas estruturas cocleares, inclusive o giro coclear apical, o giro coclear médio e o giro coclear basal. A correlação da ocorrência de hidropsia endolinfática entre as várias partes da orelha interna foi determinada. Resultados: Hidropsia endolinfática sintomática foi detectada no lado afetado em todos os pacientes, enquanto hidropsia endolinfática assintomática foi detectada no lado contralateral não afetado em 32 pacientes (18,0%). No lado afetado, o giro apical da cóclea e o giro coclear médio demonstraram taxas significativamente mais altas de hidropsia endolinfática do que o giro basal e o vestíbulo. A gravidade da hidropsia endolinfática diminuiu gradualmente do giro apical da cóclea para o giro basal. No lado contralateral, a incidência e o grau da hidropsia endolinfática assintomática detectada foram significantemente maiores nas cócleas do que nos vestíbulos (p < 0,05), sem diferença significante entre os giros cocleares. Conclusões: A progressão da hidropsia endolinfática parece ser direcional, iniciando-se na cóclea. A sua ordem da gravidade diminui gradualmente do giro apical da cóclea para o giro basal e, em seguida, para o vestíbulo. A hidropsia endolinfática no vestíbulo está associada à doença de Ménière sintomática.

Medios de contraste intravascular en tomografía computada y resonancia magnética: lo que el clínico necesita saber / Intravascular contrast media in computed tomography and magnetic resonance imaging: what the clinician needs to know

Introducción: los medios de contraste en radiología se utilizan para mejorar la visibilidad de los tejidos normales y patológicos, lo que permite distinguirlos entre sí mediante la modificación de las características de imagen de los tejidos. Permite no solo una mejor evaluación morfológica de las lesiones, sino también una evaluación cinética funcional y de contraste. Objetivos: presentar una revisión actualizada sobre los medios de contraste intravascular en radiología, con énfasis en los conceptos que el médico clínico no radiólogo debe tener presente al momento de su indicación. Métodos: se realizó una revisión bibliográfica de literatura radiológica relevante sobre medios de contraste intravascular: clasificación, indicaciones, contraindicaciones y precauciones que debe adoptar el médico clínico. Resultados: aunque los medios de contraste en radiología tienen un excelente perfil de seguridad, su uso no está exento de riesgos y debe basarse en criterios apropiados después de una evaluación clínica exhaustiva, ponderando riesgos y beneficios para cada paciente individual. Conclusión: la comunicación entre médicos tratantes, nefrólogos y radiólogos es funda-mental para evaluar casos clínicos complejos o que requieran consideraciones especiales al momento de indicar la administración de un medio de contraste intravascular.

Introduction: Imaging contrast media are used to enhance the visibility of normal and pathologic tissues, allowing distinction of one another by modifying tissue imaging characteristics. This allows both enhanced morphologic assessment of lesions and also contrast kinetics evaluation. Objectives: To present an updated review on intravascular imaging contrast media. Emphasis will be put on useful concepts that general physicians must take into account when indicating contrast-enhanced imaging studies.Methodology: A bibliographic review of relevant imaging literature on intravascular contrast media was performed: classification, appropriate indications, contraindications, and tips for proper use by the general physician. Results: Although imaging contrast media have an excellent safety profile, its use is not risk-free and must be based on appropriateness criteria applied after a thorough clinical evaluation, balancing the risks and benefits for each patient. In particular, intravascular contrast media, such as those based on iodine for computed tomography and gadolinium chelates for magnetic resonance imaging, must be used with caution. Conclusion: Effective communication between radiologists and referring physicians is key in the evaluation of complex cases that require protocol adjustments when considering the use of intravascular contrast media for imaging studies.

Determinação do Tecido Cicatricial do Miocárdio no Fenômeno de Fluxo Coronário Lento e a Relação entre a Quantidade de Tecido Cicatricial e o Nt-ProBNP / Determination of Myocardial Scar Tissue in Coronary Slow Flow Phenomenon and The Relationship Between Amount of Scar Tissue and Nt-ProBNP

Resumo Fundamento A fisiopatologia e o prognóstico não estão claramente determinados nos pacientes com fenômeno do fluxo coronário lento (FCL). Esses pacientes apresentam várias condições clínicas, que variam desde quadro assintomático até internação hospitalar com morte cardíaca súbita. Objetivos Nosso objetivo foi avaliar os achados da ressonância magnética cardíaca (RMC) com o realce tardio pelo gadolínio (RTG), como um indicador de fibrose miocárdica. Também buscamos determinar a relação entre a presença de fibrose miocárdica e os níveis de NT-proBNP em pacientes com FCL na artéria coronária descendente anterior esquerda (DAE). Métodos Ao todo, 35 pacientes, entre 31 e 75 anos de idade, foram incluídos. Os pacientes estudados (n=19) apresentaram artérias coronárias epicárdicas normais na angiografia, mas tinham FCL na DAE. O grupo controle de pacientes (n=16) apresentou artérias coronárias epicárdicas normais e níveis de escore TIMI normais na angiografia. Em ambos os grupos, os pacientes foram examinados com RMC para a detecção de presença de fibrose miocárdica. Além disso, níveis plasmáticos de NT-proBNP foram medidos. Valores de p < 0,05 foram considerados significativos. Resultados A taxa de fibrose miocárdica foi significativamente maior na RMC para os pacientes com FCL (p=0.018). Uma quantidade variável de tecido cicatricial foi detectada no ápice ventricular esquerdo em 7 pacientes e nas regiões inferior e inferolateral em 3 pacientes. Não foram observadas diferenças nos níveis de NT-proBNP nos pacientes com FCL. Entretanto, os níveis de NT-proBNP foram maiores nos pacientes com FCL, que apresentaram fibrose miocárdica na RMC (p=0.022). Conclusões Em suma, o RTG na RMC mostrou que a cicatriz miocárdica isquêmica pode estar presente nos pacientes com FCL. Esses resultados indicam que o FCL pode nem sempre ser inofensivo. (Arq Bras Cardiol. 2020; 114(3):540-551)

Abstract Background Pathophysiology and prognosis are not clearly determined in patients with the coronary slow flow phenomenon (CSFP). These patients present with various clinical conditions ranging from being asymptomatic to being admitted with sudden cardiac death. Objectives We aimed at assessing the findings of late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR) as an indicator of myocardial fibrosis. We also aimed at determining the relationship between the presence of myocardial fibrosis and NT-proBNP levels in patients with CSFP in the left anterior descending coronary artery (LAD). Methods A total of 35 patients were enrolled within an age range of 31-75. The study patients (n=19) had normal epicardial coronary arteries at angiography, but they presented with CSFP in the LAD. The control group patients (n=16) had normal epicardial coronary arteries and TIMI scores at normal levels in angiography. In both groups, the patients were examined with CMR for the presence of myocardial fibrosis. In addition, plasma NT-proBNP levels were measured. A p-value < 0.05 was considered significant. Results The rate of myocardial fibrosis was significantly higher in CMR in the patients with CSFP (p=0.018). A variable amount of myocardial scar tissue was detected at the left ventricular apex in 7 patients and at the inferior and inferolateral regions in 3 patients. There was no difference in the level of NT-proBNP in patients with CSFP. However, the NT-proBNP levels were higher in patients with CSFP, who had scar tissue in CMR (p=0.022). Conclusions In conclusion, LGE in CMR showed that ischemic myocardial scarring may exist in patients with CSFP. These results indicate that CSFP may not always be innocent. (Arq Bras Cardiol. 2020; 114(3):540-551)