RESUMEN
MicroRNAs (miRNAs) are small noncoding RNA molecules that act as major regulators of gene expression at the post-transcriptional level. As the potential applications of miRNAs in the diagnosis and treatment of human diseases have become more evident, many studies of hypertrophic cardiomyopathy (HCM) have focused on the systemic identification and quantification of miRNAs in biofluids and myocardial tissues. HCM is a hereditary cardiomyopathy caused by mutations in genes encoding proteins of the sarcomere. Despite overall improvements in survival, progression to heart failure, stroke, and sudden cardiac death remain prominent features of living with HCM. Several miRNAs have been shown to be promising biomarkers of HCM; however, there are many challenges to ensuring the validity, consistency, and reproducibility of these biomarkers for clinical use. In particular, miRNA testing may be limited by pre-analytical and analytical caveats, making our interpretation of results challenging. Such factors that may affect miRNA testing include sample type selection, hemolysis, platelet activation, and renal dysfunction. Therefore, researchers should be careful when developing appropriate standards for the design of miRNA profiling studies in order to ensure that all results provided are both accurate and reliable. In this review, we discuss the application of miRNAs as biomarkers for HCM.
Asunto(s)
Cardiomiopatía Hipertrófica , Enfermedades Cardiovasculares , MicroARN Circulante , MicroARNs , Biomarcadores , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Humanos , MicroARNs/genética , Reproducibilidad de los ResultadosRESUMEN
The comprehensive assessment of patients with hypertrophic cardiomyopathy is a complex process, with each step concurrently focusing on confirmation of the diagnosis, differentiation between sarcomeric and non-sarcomeric disease (phenocopy), and prognostication. Novel modalities such as genetic testing and advanced imaging have allowed for substantial advancements in the understanding of this condition and facilitate patient management. However, their availability is at present not universal, and interpretation requires a high level of expertise. In this setting, electrocardiography, a fast and widely available method, still retains a significant role in everyday clinical assessment of this population. In our review, we follow a stepwise approach for the interpretation of each electrocardiographic segment, discussing clinical implications of electrocardiographic patterns in sarcomeric disease, their value in the differential diagnosis from phenocopies, and impact on patient management. Outlining the substantial amount of information to be obtained from a simple tracing, we exhibit how electrocardiography is likely to remain an integral diagnostic tool in the future as well.
Asunto(s)
Cardiomiopatía Hipertrófica , Cardiomiopatía Hipertrófica/diagnóstico , Diagnóstico Diferencial , Electrocardiografía , Pruebas Genéticas , Humanos , FenotipoAsunto(s)
Corticoesteroides/administración & dosificación , Ecocardiografía/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Metotrexato/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Arteria Pulmonar , Arteritis de Takayasu , Adulto , Femenino , Humanos , Inmunosupresores/administración & dosificación , Imagen por Resonancia Magnética/métodos , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/tratamiento farmacológico , Arteritis de Takayasu/fisiopatología , Resultado del TratamientoRESUMEN
Troponin (I or T) is the principal marker of myocardial injury used in clinical practice. Although immune-based methods to determine troponin I levels are generally reliable, the presence of human antibodies interfering with the assays components could lead to erroneous results. In this report, we will discuss the case of a patient with misleadingly elevated troponin I due to high rheumatoid factor titer and provide an insight into the responsible molecular mechanisms.
Asunto(s)
Troponina I/sangre , Anciano , Artritis Reumatoide/sangre , Reacciones Falso Positivas , Humanos , Masculino , Infarto del Miocardio/sangre , Factor Reumatoide/sangre , Factor Reumatoide/inmunología , Troponina I/inmunologíaRESUMEN
Periostin, a secreted matricellular protein, has been implicated in cardiac extracellular matrix remodeling and fibrosis. Evidence suggest that periostin stimulates cardiomyocyte hypertrophy. The current study aims to investigate the extent of periostin expression in patients with advanced Hypertrophic Cardiomyopathy (HCM) and its correlation with fibrosis and hallmark histopathological features of the disease. Interventricular septal tissue from thirty-nine HCM patients who underwent myectomy and five controls who died from non-cardiac causes was obtained. Staining with Masson's Trichrome and immunohistochemistry were used to localize fibrosis and periostin respectively. The extent of fibrosis and the expression of periostin were defined as the stained percentage of total tissue area using digital pathology software. Periostin expression was higher in HCM patients compared to controls (p<0.0001), positively correlated with the extent of fibrosis (r = 0.82, p<0.001), positively correlated with maximal interventricular septal thickness (Rho = 0.33, p = 0.04) and negatively correlated with LVEF (r = -0.416, p = 0.009). Periostin was approximately co-localized with fibrosis. Mean periostin expression was lower in patients with mild grade cardiomyocyte hypertrophy compared to those with moderate grade (p = 0.049) and lower in patients with mild grade replacement fibrosis compared to moderate grade (p = 0.036). In conclusion, periostin is overexpressed in advanced HCM, correlated with fibrosis and possibly related to cardiomyocyte hypertrophy.
Asunto(s)
Cardiomiopatía Hipertrófica , Cardiopatías Congénitas , Humanos , Miocitos Cardíacos/patología , Fibrosis , Cardiopatías Congénitas/patología , Hipertrofia/patologíaRESUMEN
Hypertrophic cardiomyopathy (HCM) is a diverse inherited disease affecting 1 in 500 individuals irrespective of gender and ethnicity. A fraction of HCM patients will eventually develop drug refractory dynamic obstruction of the left ventricular outflow tract. For such patients, septal myectomy is the procedure of choice to alleviate their symptoms and improve their quality of life. The current histopathological study, the first from the Greek region, aims to examine the hallmark histopathological characteristics of Hypertrophic Obstructive Cardiomyopathy in a population of patients undergoing septal myectomy at a single center over a ten year period. Medical records and histopathology specimens of thirty nine (n=39) patients were evaluated. The sample comprised 22 males (56.4%) and 17 females (43.6%). Mean patient age at myectomy was 53.9±16.7 years, ranging from 12 to 79 years. Maximal IVS thickness on echocardiography was available for 35 patients with a median value of 2.08cm. Peak resting LVOT Pressure Gradient was available for 33 patients with a mean value of 104.88±44.20 mmHg. Central tendency of each histopathological attribute expressed as the median value was: moderate for myocyte hypertrophy, mild for cytoplasmic vacuolization, moderate for subendocardial fibrosis, moderate for interstitial fibrosis, mild for replacement fibrosis, moderate for myofibrillar disarray and mild for capillary stenosis. Myocyte hypertrophy, present in all specimens, was positively correlated with maximal IVS thickness (tau-b=0.43, p=0.002). Replacement fibrosis was positively correlated with the grade of microvascular stenosis (tau-b=0.45, p=0.004). LVEF was negatively correlated with the grade of interstitial fibrosis (tau-b=-0.43, p=0.035) and with the extent of myocardial fiber disarray (tau-b=-0.42, p=0.034). Histopathological attributes were not correlated with patient gender or age thus proving that HCM has a histological phenotype unique to each patient, mainly depending on each specific sarcomeric mutation.
Asunto(s)
Cardiomiopatía Hipertrófica/patología , Fibrosis/patología , Tabiques Cardíacos , Histología , Cardiomiopatía Hipertrófica/genética , Ecocardiografía , Femenino , Grecia , Tabiques Cardíacos/patología , Tabiques Cardíacos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetic disease of the myocardium that is characterized by phenotypic variability among patients. miR-146a is a small non-coding RNA that is well known for its role in inflammation and myocardial hypertrophy. The aim of this study is to evaluate the role of miR-146a as a candidate genetic factor influencing HCM phenotype. METHODS: In this study, 140 HCM patients and 112 control individuals were genotyped for the rs2910164 single nucleotide polymorphism (SNP) in the MIR146A gene; using this data, the correlation between different genotypes and clinical features of the disease were determined. Additionally, plasma levels of miR-146a-5p were determined in 50 HCM patients and 30 control individuals by using qPCR. RESULTS: The incidence of GC and CC genotypes were significantly lower in HCM patients (odds ratio (OR) = 0.5 [0.3-0.8], p = 0.007). The GC/CC genotypes in the dominant genetic model positively correlated with the presence of left ventricle outflow tract (LVOT) obstruction (OR = 2.3 [1.2-4.7] and p = 0.018), a higher left ventricle mass index (118 ± 47 g/m2 vs 92 ± 42 g/m2 and p = 0.02), and increased left ventricle end-diastolic diameter (4.66 ± 0.64cm vs 4.39 ± 0.7cm and p = 0.026). Atrial fibrillation was significantly higher in patients homozygous for the C allele (OR = 10.6 [2-55], p = 0.003). Interestingly, the plasma levels of miR-146a-5p were significantly increased in HCM patients with LVOT obstruction. CONCLUSION: Our findings indicate that the C allele of the rs2910164 SNP might be under negative selection in HCM patients. Additionally, plasma levels of miR-146a-5p and GC/CC genotypes are indicative of the obstructive phenotype in HCM patients.
Asunto(s)
Cardiomiopatía Hipertrófica , MicroARNs , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Ventrículos Cardíacos , Humanos , MicroARNs/genética , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence the OPG/RANK/RANKL signaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age. METHODS: Serum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender. RESULTS: Plasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls. CONCLUSIONS: Our results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Osteoprotegerina/sangre , Hormona Paratiroidea/sangre , Ligando RANK/sangre , Receptor Activador del Factor Nuclear kappa-B/sangre , Vitamina D/sangre , Adolescente , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Pronóstico , Valores de ReferenciaRESUMEN
Two-dimensional speckle tracking echocardiography represents a novel, simple, and reproducible technique for the estimation of left ventricular myocardial deformation (strain) and the evaluation of left ventricular twist mechanics. During the last few years, its clinical and prognostic implications in cardiomyopathies and hypertrophic cardiomyopathy (HCM), in particular, have been rapidly increasing. Reduced global longitudinal strain is associated with more severe disease and confers an increased risk for major cardiac events, independently of other clinical and echocardiographic risk factors. Left ventricular dyssynchrony also seems promising as a risk factor for sudden cardiac events. With respect to left atrial mechanics, left atrial reservoir, conduit, and contractile strain may also confer an increased prognostic value for atrial fibrillation, major cardiac events, and even sudden death. Although right ventricular global longitudinal strain is impaired in HCM compared with healthy controls and individuals with physiological hypertrophy, its prognostic significance is currently unknown. Conclusively, 2-dimensional speckle tracking imaging seems promising for HCM. However, future studies are needed to incorporate this new imaging technique in the standard evaluation of an HCM individual.
Asunto(s)
Cardiomiopatía Hipertrófica/diagnóstico , Ecocardiografía/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Contracción Miocárdica/fisiología , Cardiomiopatía Hipertrófica/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , PronósticoRESUMEN
BACKGROUND: miR-29a is a small non-coding RNA that is known to repress collagen synthesis. Interestingly, elevated plasma miR-29a was reported to correlate with pronounced myocardial fibrosis in patients with hypertrophic cardiomyopathy. The objective of this study was to elucidate the origin of plasma miR-29a, and evaluate its significance as a biomarker. METHODS: miR-29a expression was evaluated in plasma (n=50) and myocardial samples (n=4) from patients with hypertrophic cardiomyopathy using RT-qPCR. RESULTS: Although miR-29a was highly expressed in the myocardium, miR-29a plasma levels did not show any correlation with serum troponin I levels (rs=-0.12, p=0.43), and the heart does not release significant amounts of miR-29a into the circulation via exosome secretion. Conversely, miR-29a was present in red blood cells, and plasma levels correlated significantly with markers of hemolysis: lactic dehydrogenase (rs=0.36, p=0.01) and the absorbance of oxyhemoglobin at 414nm (rs=0.39, p=0.006). Furthermore, the association between serum haptoglobin and the maximal blood flow velocity in the left ventricle outflow tract (rs=-0.42, p=0.008) indicated that intravascular hemolysis is a manifestation of the disease. CONCLUSIONS: miR-29a is highly expressed in myocardial tissue from patients with hypertrophic cardiomyopathy. In contrast, plasma miR-29a is primarily of nonmyocardial origin and is correlated significantly with the extent of hemolysis observed in these patients.
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Cardiomiopatía Hipertrófica/sangre , Hemólisis , MicroARNs/sangre , Adulto , Biomarcadores/sangre , Cardiomiopatía Hipertrófica/genética , Humanos , MicroARNs/genética , Reacción en Cadena en Tiempo Real de la PolimerasaAsunto(s)
Cardiomiopatía Dilatada , Cardiomiopatía Hipertrófica , Enfermedad por Depósito de Glucógeno de Tipo IIb , Enfermedad por Depósito de Glucógeno de Tipo IIb/diagnóstico , Enfermedad por Depósito de Glucógeno de Tipo IIb/epidemiología , Enfermedad por Depósito de Glucógeno de Tipo IIb/genética , HumanosRESUMEN
Hypertrophic cardiomyopathy is the most common monogenic disorder in cardiology. Despite important advances in understanding disease pathogenesis, it is not clear how flaws in individual sarcomere components are responsible for the observed phenotype. The aim of this article is to provide a brief interpretative analysis of some currently proposed pathophysiological mechanisms of hypertrophic cardiomyopathy, with a special emphasis on alterations in the cardiac mechanical properties.
Asunto(s)
Cardiopatías Congénitas , Entrenamiento de Fuerza , Humanos , Respiración , Músculos RespiratoriosAsunto(s)
Artritis Reumatoide/sangre , Troponina I/análisis , Troponina T/análisis , Síndrome Coronario Agudo/diagnóstico por imagen , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Angiografía Coronaria/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente , Sensibilidad y EspecificidadRESUMEN
Acute intoxication from the pesticide aluminium phosphide is a relatively rare, life-threatening condition in which cardiovascular decompensation is the most feared problem. We report the case of a patient exposed to aluminium phosphide-liberated phosphine gas. It resulted in the development of a gastroenteritis-like syndrome accompanied by severe reduction in white blood cell numbers as an early and prominent manifestation. By affecting important physiological processes such as mitochondrial function and reactive oxygen species homeostasis, phosphine could cause severe toxicity. After presenting the characteristics of certain leucocyte subpopulations we provide the current molecular understanding of the observed leukopenia which in part seems paradoxical.
Asunto(s)
Accidentes Domésticos , Compuestos de Aluminio/envenenamiento , Leucopenia/inducido químicamente , Plaguicidas/envenenamiento , Fosfinas/envenenamiento , Análisis Químico de la Sangre , Servicio de Urgencia en Hospital , Estudios de Seguimiento , Grecia , Humanos , Leucopenia/patología , Masculino , Persona de Mediana Edad , Medición de RiesgoRESUMEN
Twenty-three years ago, numb was identified as a critical regulator in Drosophila sensory organ precursor cell asymmetric divisions. Beyond the recently recognized role in carcinogenesis, Numb seems to be important in Alzheimer's disease. This assertion comes from the involvement in various processes such as synapse morphogenesis, amyloid precursor protein trafficking, notch signaling, and neurogenesis. The purpose of the present mini-review is to provide the current picture of Numb's participation in mechanisms underlying Alzheimer's disease pathogenesis and emphasize potential aspects for future research.