[Factors associated with left ventricular diastolic dysfunction in adults from a region of the Andes in Peru]. / Factores asociados con la disfunción diastólica del ventrículo izquierdo en adultos de una región de los Andes en Perú.

Objective: To determine the factors associated with left ventricular diastolic dysfunction (LVDD) in adults residing in a region of the Andes in Peru. Method: A case-control study was conducted on adults living at an altitude of more than 3000 meters in Peru. Cases consisted of patients diagnosed with LVDD through echocardiography, whereas controls were adults without LVDD, as confirmed by echocardiography. Results: A total of 50 cases and 100 controls were included in the study. Among them, 38.7% had high blood pressure, and 41.3% were overweight. Upon adjusted analysis, age 60 or older (aOR: 4.06; 95%CI: 1.29-12.8), female sex (aOR: 2.24; 95%CI: 1.01-4.96) and left ventricular hypertrophy (aOR: 3.17; 95%CI: 1.41-7.17) were identified as statistically significant factors associated with LVDD. Conclusions: The risk of LVDD is associated with older adults, female gender, and left ventricular hypertrophy among individuals residing above 3000 meters altitude in a region of the Andes, in Peru.

Objetivo: Determinar los factores asociados con la disfunción diastólica del ventrículo izquierdo (DDVI) en adultos de una región de los Andes, en Perú. Método: Estudio de casos y controles en adultos residentes a más de 3000 metros de altitud en Perú. Los casos fueron pacientes adultos diagnosticados con DDVI por ecocardiografía, y los controles fueron adultos sin DDVI por ecocardiografía. Resultados: Se incluyeron 50 casos y 100 controles. El 38.7% tuvieron hipertensión arterial y el 41.3% sobrepeso. En el análisis ajustado, la edad de 60 o más años (ORa: 4.06; IC95%: 1.29-12.8), el sexo femenino (ORa: 2.24; IC95%: 1.01-4.96) y la hipertrofia ventricular izquierda (ORa: 3.17; IC95%: 1.41-7.17) fueron factores estadísticamente significativos. Conclusiones: El riesgo de DDVI estuvo asociado a los adultos mayores, las mujeres y los pacientes con hipertrofia ventricular izquierda que viven por encima de los 3000 metros de altitud en una región de los Andes, en Perú.

Agalsidase alfa long-term effect on left ventricular hypertrophy in Fabry disease.

INTRODUCTION: Fabry disease (FD) is an X-linked lysosomal storage disorder affecting glycosphingolipid metabolism. Most FD patients have cardiac involvement, mainly manifested as left ventricular hypertrophy (LVH), leading to early death due to complications (arrhythmias, valvular disease, vascular involvement). Early initiation of enzyme replacement therapy (ERT) before fibrosis development has been associated with better cardiac outcomes in terms of left ventricular mass index (LVMI) and functional parameters. METHODS: A retrospective observational study was conducted in patients with FD treated with agalsidase alfa for at least 2 years. The primary objectives were: [a] to assess the annual rate of change in LVMI; [b] to define the overall incidence of stability, regression or progression of LVMI. RESULTS: Forty-nine patients were included in the final analysis, with a median follow-up of 7 years. The overall change in LVMI was 0.38 g/m2.73/year, without significant influence of baseline LVH, gender, age at ERT initiation, LV ejection fraction, body mass index, renal disease, and classical cardiovascular risk factors. Long-term ERT with agalsidase alfa was associated with stabilization of LVMI in 98% of patients with FD and was independent of the same covariables. CONCLUSION: Our results are in line with previous literature of comparable FD populations and probably represent the first study of its kind in Argentina. We here highlight the importance of cardiac morphometric stability as a positive outcome of ERT.

Introducción: La enfermedad de Fabry (EF) es una enfermedad de almacenamiento lisosomal ligada al cromosoma X que afecta el metabolismo de glicoesfingolípidos. La mayoría de pacientes EF tienen afectación cardíaca, manifestada principalmente como hipertrofia ventricular izquierda (HVI), que conduce a muerte prematura secundaria a complicaciones (arritmias, valvulopatías, afectación vascular). El tratamiento de reemplazo enzimático (TRE) precoz, iniciado antes del desarrollo de la fibrosis, se relaciona con mejores resultados cardíacos en términos del índice de masa ventricular izquierda (IMVI) y parámetros funcionales. Métodos: Se realizó un estudio retrospectivo observacional en que se incluyeron pacientes con EF tratados con agalsidasa alfa por al menos 2 años. Los objetivos primarios fueron: [a] evaluar el cambio anual del IMVI; [b] definir la incidencia global de estabilidad, regresión o progresión del IMVI. Resultados: Se incluyeron 49 pacientes, con seguimiento (mediana) de 7 años. El cambio global en el IMVI fue 0.38 g/m2.73/año, sin influencia significativa de HVI basal, sexo, edad de inicio de TRE, fracción de eyección del VI, índice de masa corporal, insuficiencia renal y factores de riesgo cardiovascular clásicos. La TRE a largo plazo con agalsidasa alfa se relacionó con la estabilización del IMVI en el 98% de los pacientes con EF, independientemente de las mismas covariables. Conclusión: Nuestros resultados están en línea con la bibliografía previa de poblaciones comparables y, probablemente, representan el primer estudio de este tipo en Argentina. Se destaca la importancia de la estabilidad morfométrica cardíaca como resultado positivo de la TRE.

Left ventricular hypertrophy: hypertensive or hypertrophic cardiomyopathy? What a dilemma! A case report / Hipertrofia ventricular izquierda: ¿cardiopatía hipertensiva o miocardiopatía hipertrófica? ¡Vaya dilema! Reporte de caso

Abstract In the presence of the left ventricle hypertrophy (LVH), the differential diagnosis with hypertrophic cardiomyopathy (HCM) or some phenocopy must be always considered, which can be easily suspected when the hypertrophy is markedly asymmetric. However, when the hypertrophy is homogeneous, especially if the patient has concomitant hypertension, it may be a challenge to distinguish between hypertensive and HCM, although some clinical features may help us to suspect it. In addition, patients with HCM may present with exertional angina due to microcirculation involvement in the setting of the hypertrophy itself or dynamic obstruction in the left ventricular outflow tract, but in some cases, the presence of concomitant coronary artery disease must be suspected as the cause of angina, especially if the patient has an intermediate or high-risk probability of having ischemic heart disease. We present the case of a 46-year-old Afro-American man with poorly controlled hypertension who was found to have severe LVH, and who presented with symptoms of exertional angina during follow-up. We will review the clinical features that can help us in the differential diagnosis in this context.

Resumen Ante la presencia de hipertrofia del ventrículo izquierdo (HVI), siempre se debe considerar el diagnóstico diferencial con la miocardiopatía hipertrófica (MCH) o alguna fenocopia, que puede sospecharse fácilmente cuando la hipertrofia es marcadamente asimétrica. Además, los pacientes con MCH pueden presentar angina de esfuerzo debido a la afectación de la microcirculación en el contexto de la propia hipertrofia o si ésta condiciona obstrucción dinámica al tracto de salida del ventrículo izquierdo, pero en algunos casos debe sospecharse la presencia de enfermedad coronaria concomitante como causa de la angina, especialmente si el paciente tiene una probabilidad de riesgo intermedio o alto de padecer cardiopatía isquémica. Presentamos el caso de un varón de 46 años de afroamericana con hipertensión arterial mal controlada a quien se le detectó una HVI severa, y que durante el seguimiento presentó síntomas de angina de esfuerzo. Revisaremos las características clínicas que nos pueden ayudar en el diagnóstico diferencial en este contexto.

Prognostic Implications of Left Ventricular Hypertrophy and Mechanical Function in Fabry Disease: A Longitudinal Cohort Study.

BACKGROUND: The prognostic value of different grades of left ventricular hypertrophy (LVH) and left ventricular (LV) mechanical function in Fabry disease is unclear. We aimed to evaluate the association between the severity of LVH, LV mechanical function, and clinical outcomes in Fabry disease. METHODS: We conducted a retrospective cohort study from a single-center registry of adult patients with Fabry disease. Left ventricular mass index (LVMI) was measured by echocardiography. The severity of LVH was categorized by LVMI using the sex-specific cutoff values. Left ventricular mechanical function was measured as LV global longitudinal strain (GLS) by speckle-tracking analysis. The primary outcome was a composite of major adverse cardiovascular events (MACE) at 5 years, including heart failure hospitalization, sustained ventricular tachycardia, acute ischemic stroke, and all-cause mortality. RESULTS: The study included 268 patients (age 50.4 ± 15.4 years, men 46.6%) with Fabry disease (83.2% IVS4+919G > A mutation), and 106 patients (39.6%) had LVH. Patients with mild, moderate, or severe LVH had 5-year MACE rates of 7.4%, 10%, and 30.5%, respectively (P < .001). Moreover, patients with impaired LV GLS (<14.1%) had a higher 5-year MACE rate than those with preserved LV GLS (32.1% vs 2.4%, P < .001). Severe LVH was an independent predictor of MACE compared with absence of LVH (adjusted hazard ratio, 12.73; 95% CI, 1.3-124.71; P = .03), after adjusting for age, sex, hypertension, hyperlipidemia, atrial fibrillation, renal function, average E/e', enzyme replacement therapy, and LV GLS. Patients with severe LVH and impaired LV GLS had the highest incidence for MACE (log-rank P < .05), irrespective of sex, genotypes, and whether receiving enzyme replacement therapy or not. CONCLUSIONS: Sex-specific grading of LVH by LVMI is practical for risk stratification in patients with Fabry disease, and impaired LV GLS further refines the prognostication.

Left ventricular hypertrophy: hypertensive or hypertrophic cardiomyopathy? What a dilemma! A case report.

In the presence of the left ventricle hypertrophy (LVH), the differential diagnosis with hypertrophic cardiomyopathy (HCM) or some phenocopy must be always considered, which can be easily suspected when the hypertrophy is markedly asymmetric. However, when the hypertrophy is homogeneous, especially if the patient has concomitant hypertension, it may be a challenge to distinguish between hypertensive and HCM, although some clinical features may help us to suspect it. In addition, patients with HCM may present with exertional angina due to microcirculation involvement in the setting of the hypertrophy itself or dynamic obstruction in the left ventricular outflow tract, but in some cases, the presence of concomitant coronary artery disease must be suspected as the cause of angina, especially if the patient has an intermediate or high-risk probability of having ischemic heart disease. We present the case of a 46-year-old Afro-American man with poorly controlled hypertension who was found to have severe LVH, and who presented with symptoms of exertional angina during follow-up. We will review the clinical features that can help us in the differential diagnosis in this context.

Ante la presencia de hipertrofia del ventrículo izquierdo (HVI), siempre se debe considerar el diagnóstico diferencial con la miocardiopatía hipertrófica (MCH) o alguna fenocopia, que puede sospecharse fácilmente cuando la hipertrofia es marcadamente asimétrica. Además, los pacientes con MCH pueden presentar angina de esfuerzo debido a la afectación de la microcirculación en el contexto de la propia hipertrofia o si ésta condiciona obstrucción dinámica al tracto de salida del ventrículo izquierdo, pero en algunos casos debe sospecharse la presencia de enfermedad coronaria concomitante como causa de la angina, especialmente si el paciente tiene una probabilidad de riesgo intermedio o alto de padecer cardiopatía isquémica. Presentamos el caso de un varón de 46 años de afroamericana con hipertensión arterial mal controlada a quien se le detectó una HVI severa, y que durante el seguimiento presentó síntomas de angina de esfuerzo. Revisaremos las características clínicas que nos pueden ayudar en el diagnóstico diferencial en este contexto.

Diferenças entre Duas Condições Cardíacas Hipertróficas Distintas: Doença de Fabry Versus Cardiomiopatia Hipertrófica / Differences Between Two Distinct Hypertrophic Cardiac Conditions: Fabry Disease versus Hypertrophic Cardiomyopathy

Resumo Fundamento A cardiomiopatia hipertrófica (CMH) e a doença de Fabry (DF) são doenças herdadas geneticamente com características fenotípicas de hipertrofia ventricular esquerda (HVE) que causam resultados cardíacos adversos. Objetivos Investigar as diferenças demográficas, clínicas, bioquímicas, eletrocardiográficas (ECG) e ecocardiográficas (ECO) entre CMH e DF. Métodos 60 pacientes com CMH e 40 pacientes com DF foram analisados retrospectivamente como uma subanálise do "estudo LVH-TR" após exclusão de pacientes com fibrilação atrial, ritmo de estimulação, bloqueios de ramo e bloqueios atrioventriculares (AV) de segundo e terceiro graus. O nível de significância foi aceito como <0,05. Resultados O sexo masculino (p=0,048) e a creatinina (p=0,010) são significativamente maiores a favor da DF; entretanto, infradesnivelamento do segmento ST (p=0,028), duração do QT (p=0,041), espessura do septo interventricular (SIVd) (p=0,003), espessura da parede posterior (PWd) (p=0,009), insuficiência mitral moderada a grave (IM) (p=0,013) e o índice de massa ventricular esquerda (IMVE) (p=0,041) são significativamente maiores a favor da CMH nas análises univariadas. Na análise multivariada, a significância estatística apenas permanece na creatinina (p=0,018) e na duração do intervalo QT (0,045). A DF foi positivamente correlacionada com a creatinina (rho=0,287, p=0,004) e a CMH foi positivamente correlacionada com o PWd (rho=0,306, p=0,002), IVSd (rho=0,395, p<0,001), IM moderada-grave (rho= 0,276, p<0,005), IMVE (rho=0,300, p=0,002), espessura relativa da parede (ERP) (rho=0,271, p=0,006), duração do QT (rho=0,213, p=0,034) e depressão do segmento ST (rho =0,222, p=0,026). Conclusão Características bioquímicas, ECG e ECO específicas podem auxiliar na diferenciação e no diagnóstico precoce da CMH e da DF.

Abstract Background Hypertrophic cardiomyopathy (HCM) and Fabry disease (FD) are genetically inherited diseases with left ventricular hypertrophy (LVH) phenotype characteristics that cause adverse cardiac outcomes. Objectives To investigate the demographic, clinical, biochemical, electrocardiographic (ECG), and echocardiographic (ECHO) differences between HCM and FD. Methods 60 HCM and 40 FD patients were analyzed retrospectively as a subanalysis of the 'LVH-TR study' after excluding patients with atrial fibrillation, pace rhythm, bundle branch blocks, and second and third-degree atrioventricular (AV) blocks. The significance level was accepted as <0.05. Results Male gender (p=0.048) and creatinine (p=0.010) are significantly higher in favor of FD; however, ST depression (p=0.028), QT duration (p=0.041), interventricular septum thickness (IVSd) (p=0.003), posterior wall thickness (PWd) (p=0.009), moderate-severe mitral regurgitation (MR) (p=0.013), and LV mass index (LVMI) (p=0.041) are significantly higher in favor of HCM in the univariate analyses. In multivariate analysis, statistical significance only continues in creatinine (p=0.018) and QT duration (0.045). FD was positively correlated with creatinine (rho=0.287, p=0.004) and HCM was positively correlated with PWd (rho=0.306, p=0.002), IVSd (rho=0.395, p<0.001), moderate-severe MR (rho=0.276, p<0.005), LVMI (rho=0.300, p=0.002), relative wall thickness (RWT) (rho=0.271, p=0.006), QT duration (rho=0.213, p=0.034) and ST depression (rho=0.222, p=0.026). Conclusion Specific biochemical, ECG, and ECHO characteristics can aid in the differentiation and early diagnosis of HCM and FD.

Reclassification of Adolescent Ambulatory Prehypertension and Unclassified Blood Pressures by 2022 American Heart Association Pediatric Ambulatory Blood Pressure Monitoring Guidelines.

OBJECTIVE: To describe the epidemiology of reclassification of prehypertensive and unclassified adolescents by 2022 American Heart Association pediatric ambulatory blood pressure monitoring (ABPM) guidelines, and to evaluate the association of the new diagnostic categories with left ventricular hypertrophy (LVH). STUDY DESIGN: A single-center, retrospective review of ABPM reports from adolescents 13-21 years old, from 2015 through 2022, was performed. Adolescents with prehypertension or unclassified by 2014 guidelines were reclassified by 2022 definitions. Logistic regression models evaluated the association of reclassification phenotypes with LVH. RESULTS: A majority of prehypertensive adolescents reclassified to hypertension (70%, n = 49/70). More than one-half (57%, n = 28/49) of the hypertension was isolated nocturnal hypertension, and 80% was systolic hypertension. Reclassification to hypertension was more common in males. The majority (55.6%) of unclassified adolescents were reclassified to normotension. No demographic or clinical variables were associated with reclassification categories. LVH was not associated with hypertension in the reclassified prehypertensive or unclassified groups. CONCLUSIONS: The 2022 ABPM guidelines clearly define blood pressure phenotypes. However, reclassification to hypertension was not associated with an increased odds of LVH. Because most prehypertensive adolescents reclassified as hypertensive by nighttime BPs alone, this study highlights the lowered threshold for nocturnal hypertension. Prospective studies in larger, well-defined cohorts are needed to describe better the predictive value of 2022 BP phenotypes for target organ damage.

Valor del electrocardiograma en el diagnóstico de la hipertrofia ventricular izquierda en la hipertensión arterial

Introducción: la hipertrofia ventricular izquierda es un factor de riesgo independiente de enfermedad cardiovascular. Existen diversos criterios electrocardiográficos para el diagnóstico, con distintas sensibilidades y especificidades. Objetivo: determinar el valor diagnóstico de los criterios electrocardiográficos de hipertrofia del ventrículo izquierdo en comparación a la ecocardiografía transtorácica en personas adultas con hipertensión arterial. Material y método: diseño observacional, descriptivo, retrospectivo de corte transversal, tipo prueba diagnóstica, que incluyó a pacientes adultos con diagnóstico de hipertensión arterial internados en las salas de Clínica Médica del Hospital de Clínicas, Paraguay, desde agosto del 2022 a agosto del 2023. Se determinaron las variables demográficas, criterios electrocardiográficos (Sokolov-Lyon, Cornell, Lewis, Peguero Lo Presti) y ecocardiográficos de hipertrofia ventricular izquierda. Resultados: se evaluaron 517 electrocardiogramas y ecocardiografías de pacientes hipertensos. Según criterio de Sokolov-Lyon la sensibilidad fue 16% y la especificidad 70% para el diagnóstico de la hipertrofia ventricular izquierda; por criterios de Cornell la sensibilidad fue 43% y especificidad 87 %; por criterios de Lewis la sensibilidad fue 26% y especificidad 76% y por criterios de Peguero Lo Presti la sensibilidad fue 63% y la especificidad 87%. Conclusión: el criterio por electrocardiograma de hipertrofia ventricular izquierda con mayor sensibilidad fue de Peguero Lo Presti y los de mayor especificidad fueron los de Peguero Lo Presti y Cornell.

Introduction: Left ventricular hypertrophy is an independent risk factor for cardiovascular disease. There are various electrocardiographic criteria for diagnosis, with different sensitivities and specificities. Objective: To determine the diagnostic value of electrocardiographic criteria for left ventricular hypertrophy in comparison to transthoracic echocardiography in adults with arterial hypertension. Material and method: Observational, descriptive, retrospective cross-sectional design, diagnostic test type, which included adult patients with a diagnosis of arterial hypertension admitted to the Medical Clinic rooms of the Hospital de Clínicas, Paraguay, from August 2022 to August 2023. Demographic variables, electrocardiographic criteria (Sokolow-Lyon, Cornell, Lewis, Peguero Lo Presti), and echocardiographic criteria for left ventricular hypertrophy were determined. Results: Five hundred seventeen electrocardiograms and echocardiograms of hypertensive patients were evaluated. According to the Sokolow-Lyon criteria, the sensitivity was 16% and the specificity was 70% for the diagnosis of left ventricular hypertrophy; by Cornell criteria, the sensitivity was 43% and specificity 87%; by Lewis criteria, the sensitivity was 26% and specificity 76% and by Peguero Lo Presti criteria. the sensitivity was 63% and the specificity 87%. Conclusion: The electrocardiogram criterion of left ventricular hypertrophy with the greatest sensitivity was that of Peguero Lo Presti and those with the greatest specificity were those of Peguero Lo Presti and Cornell.

Miocardiopatía Hipertrófica en ausencia de criterios de hipertrofia. Serie de casos / Hypertrophic cardiomyopathy in the absence of hypertrophy criteria. Case series

La miocardiopatía hipertrófica (MCH) es la miocardiopatía hereditaria más frecuente, su principal expresión fenotípica consiste en hipertrofia ventricular izquierda (HVI) en ausencia de condiciones de carga que la justifiquen. Cuando existe una variante genética patogénica se denomina MCH sarcomérica. Los criterios diagnósticos más aceptados son HVI ≥ 15 mm en cualquier segmento o ≥ 13 en ciertas condiciones, criterios que tienen tres inconvenientes: 1) La HCM es una patología donde la HVI es evolutiva, existiendo otros elementos más precoces, pero menos precisos, como criptas, bandas musculares y alteraciones de la válvula mitral y músculos papilares; 2) Pacientes de baja estatura pueden no alcanzar estos umbrales; 3) La MCH apical no queda siempre bien representada usando estos grosores, requiriendo indexar por tamaño del paciente y/o considerar la HVI relativa (relación grosor apical / basal que no debe superar 1). Presentamos una serie de casos con genotipo confirmado para MCH que no cumplen los criterios de HVI aceptados para MCH y donde se debe individualizar el diagnóstico considerando los tres elementos señalados.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition; its phenotypic expression consists of ventricular hypertrophy (LVH) unrelated to loading conditions. In patients with a genetic pathogenic variant, the condition is termed sarcomeric HCM. Current diagnostic criteria are based on absolute left ventricular thickness, requiring ≥15 mm in any segment or ≥13 mm in particular conditions. These criteria have three pitfalls: 1) HCM is an evolving disease where LVH occurs gradually, with other early -but less precisephenotypic expressions such as myocardial crypts, muscular bands, or mitral and papillary muscle alterations; 2) Patients with short stature tend to have less LVH and do not reach the proposed thickness threshold. 3) Apical HCM is not correctly addressed in this cut-off as the heart tapers from base to apex, warranting indexing wall thickness to body size and using relative LVH in the apex (ratio from apex/base, abnormal,>1). This small case series includes three patients with a pathogenic genetic variant for HCM that doesn't satisfy the current criteria of LVH. For its precise assessment, the aforementioned points must be considered.

Enzima convertidora de angiotensina homóloga (ECA2) y actividad de ROCK en la falla cardíaca experimental / ACE 2 and ROCK activity in experimental congestive heart failure

Antecedentes: La ECA2 ha mostrado ser un regulador esencial de la funcionalidad cardíaca. En un modelo experimental de insuficiencia cardíaca (IC) con Fier, modelo de coartación de aorta (COA), se encontró activación de la vía Rho-kinasa. La inhibición de esta vía con fasudil no mejoró el remodelado cardíaco ni la disfunción sistólica. Se desconoce en este modelo, si el deterioro de la función cardíaca y activación de la vía rho-kinasa se asocia con una disminución de la ECA2 cardíaca y si la inhibición de Rho-kinasa tiene un efecto sobre la expresión de ECA2. Objetivo: Nuestro objetivo es determinar si en la falla cardaca experimental por coartación aórtica, los niveles proteicos de ECA2 en el miocardio se asocian a disfunción sistólica y cual es su interacción con la actividad de ROCK en el miocardio. Métodos: Ratones C57BL6J machos de 7-8 semanas se randomizaron en 3 grupos experimentales. Grupo COA por anudación de la aorta + vehículo; Grupo COA + Fasudil (100 mg/Kg día) por bomba osmótica desde la semana 5 post-cirugía; y grupo control o Sham. Se determinaron las dimensiones y función cardíaca por ecocardiografía. Posterior a la eutanasia, se determinaron los niveles de ECA2 del VI por Western-blot y actividad de la Rho-kinasa Resultados: En los grupos COA+vehículo y COA-FAS hubo deterioro de la función cardíaca, reflejada por la reducción de la FE (47,9 ± 1,53 y 45,5 ± 2,10, p < 0,05, respectivamente) versus SHAM (68,6 ± 1,19). Además, aumentaron las dimensiones cardíacas y hubo desarrollo de hipertrofia (0,53 ± 0,02 / 0,53 ± 0,01, p < 0,05) medida por aumento de la masa cardíaca relativa respecto del grupo SHAM (0,40 ± 0,01). En los grupos COA+vehículo y COA-FAS se encontró una disminución significativa del 35% en la expresión de ECA2 cardíaca respecto al grupo control. Conclusiones: La disfunción sistólica por coartación aórtica se asocia con aumento de la actividad de Rho-kinasa y significativa disminución de la expresión de ECA2. La inhibición de Rho-kinasa no mejoró el remodelado cardíaco, la disfunción sistólica y tampoco modificó los niveles de ECA2 cardíaca.

Background: ACE2 has been described as an essential regulator of cardiac function. In an experimental model of heart failure (HF) and heart failure reduced ejection fraction (HFrEF), the aortic coarctation (COA) model, activation of the Rho-kinase pathway of cardiac remodeling was found. Inhibition of this pathway did not improve cardiac remodeling or systolic ventricular dysfunction. It is unknown in this model whether the impairment of cardiac function and activation of the rho-kinase pathway is associated with a decrease in ACE2 and whether rho-kinase inhibition has an effect on ACE2 expression. Objective: To determine if in experimental heart failure due to aortic coarctation, ACE2 protein levels in the myocardium are associated with systolic dysfunction and what is its interaction with ROCK activity in the myocardium. Methods: Male C57BL6J mice aged 7-8 weeks were divided into 3 groups and anesthetized: One group underwent COA+ vehicle; A second group COA + Fasudil (100 mg/Kg/d) by osmotic pump from week 5 post-surgery and; the third group, control(SHAM). Echocardiograms were performed to determine cardiac dimensions and systolic function. Rats were then euthanized. Ventricular expression of ACE2, activity of the Rho-kinase pathway by MYPT-1 phosphorylation, relative cardiac mass, area and perimeter of cardiomyocytes were determined by Western blot. Results: In both COA+vehicle and COA+FAS groups there was deterioration of cardiac function, reflected in the reduction of EF (47.9 ± 1.53 and 45.5 ± 2.10, p < 0.05, respectively) versus the SHAM group (68.6 ± 1.19). In addition, cardiac dimensions and hypertrophy increased (0.53 ± 0.02 / 0.53 ± 0.01, p < 0.05) due to increased relative cardiac mass compared to the SHAM group (0.40 ± 0.01). In the COA+vehicle and COA+FAS groups a significant decrease of 35% in cardiac ACE2 expression was found compared to the control group. Conclusions: Systolic dysfunction due to aortic coarctation is associated with increased Rhokinase activity and a significant decrease in ACE2 expression. Rho-kinase inhibition did not improve cardiac remodeling, systolic dysfunction, nor did it change cardiac ACE2 levels.

Prevalence of papillary muscle hypertrophy in fabry disease.

BACKGROUND AND AIMS: Fabry disease (FD) is an X-linked genetic lysosomal disease, in which a deficit in the alpha-galactosidase A enzyme results in lysosomal build-up of globotriaosylceramide in several organs, causing cardiac, renal and cerebrovascular complications. The aim of this study was to assess the prevalence of papillary muscle hypertrophy (PMH) in patients with FD. METHODS: A group of 63 patients with FD and a positive genetic diagnosis were studied and were divided into two groups: one included 24 patients with FD and LVH and another group included 39 patients with FD and without LVH. Papillary muscles were measured from the left parasternal short axis view, defining PMH as a diastolic thickness greater than 11 mm in any diameter. RESULTS: Patients with FD and LVH had a high prevalence of anterolateral PMH (66.6%), and such prevalence was lower for the posteromedial PMH (33.3%). However, patients who had not yet developed LVH had a high prevalence of anterolateral PMH (33.3%). CONCLUSIONS: Patients with FD in the pre-clinical stage (without LVH) have a high prevalence of PMH, especially involving the anterolateral papillary muscle. This finding could be an early marker for the development of LVH, allowing to suspect the disease during its early stages, and begin enzyme replacement therapy in the appropriate patients.

The sodium borate relieves the hypertrophic damage induced during pregnancy, it improves contractibility, reduces oxidative stress and stimulates cell proliferation.

INTRODUCTION: Fetal and postnatal hypertrophy develop in response to such different exposures or illnesses the mother suffers during gestation as anti-infectious and physical agents, obesity, hypertension, diabetes, and even advanced maternal age. This gives rise to high comorbidities in the newborn; therefore, looking for alternatives that contribute to cardiac homeostasis is quite necessary to inhibit the overgrowth of myocytes. Boron-derivative compounds could play a key role in exerting a repairing effect on chronic cardiac damage induced during gestation. METHODOLOGY: The cardiotoxic effect of 6.4, 12 and 100 mg/kg of sodium tetraborate administered by oral delivery route to healthy pregnant mice was assessed. After that, the use of the chemical compound was tested in the treatment of pregnant mice previously subjected to isoproterenol (fetal hypertrophy model) on the fifth day post coitus. Prior to the sacrifice of the pups of mice an electrocardiography (ECG) was done. Morphological and histological changes of heart were assessed in newborn pups. As a damage marker, the concentration of p38 nitrogen-activated protein kinases were evaluated by using Western Blot and the levels of malondialdehyde (MDA) as well as glutathione antioxidants (GSH) and glutathione peroxidase (GPx) were tested by spectrometry. Moreover, the mRNA expression for early response genes (c-jun, c-fos y c-myc), late response (GATA-4, Mef2c, NFAT) and heart damage (ANP and BNP) was measured by qPCR real time. RESULTS: The supply of 6,4 and 12 mg/kg-sodium tetraborate favored ventricular remodeling with histological alterations. By comparison, 100 mg/kg of sodium tetraborate administered during the fetal stage did not alter neither the cardiac morphology of six-week old pups nor the p38/P-p38MAPK ratio remained the same and no oxidative stress was observed. When pregnant females treated with isoproterenol were treated with 100 mg/kg sodium tetraborate during the fetal stage, an improvement in contractility was detected in the pups with an actual reduction in myocardial fibrosis and oxidative stress, but cardiac mass increased. In addition, the expression levels of c-jun, c-myc, GATA-4, MEF2c and ANP mRNA declined in comparison with CTR. However, the hypertrophic damage mechanism was sustained by c-fos, NFAT and BNP expressions. CONCLUSIONS: The set of results achieved suggests that high concentrations of sodium tetraborate have no cardiotoxic effects. Furthermore, sodium tetraborate mitigates hypertrophy induced during pregnancy, thereby improving contractibility, reducing oxidative stress and stimulating cell proliferation. Therefore, sodium tetraborate could be an excellent prophylactic treatment administered by delivery oral route during pregnancy when there is a risk of developing fetal left ventricular hypertrophy (LVH).

Elevated Blood Pressure and Worsening Cardiac Damage During Adolescence.

OBJECTIVES: To examine the longitudinal course for the development of elevated blood pressure (BP)/hypertension and cardiac damage in adolescents. STUDY DESIGN: From the Avon Longitudinal Study of Parents and Children, UK birth cohort, 1856 (1011 female) 17-year-old adolescents were followed up for 7 years. BP and echocardiography were assessed at ages 17 and 24 years. Elevated/hypertensive BP was defined as ≥130 mm Hg systolic and ≥85 mm Hg diastolic. Left ventricular (LV) mass indexed for height2.7 (LVMI2.7) ≥51 g/m2.7 was defined as LV hypertrophy (LVH) and LV diastolic function (LVDF) E/A <1.5 as LVD dysfunction (LVDD). Data were analyzed with generalized logit mixed-effect models and cross-lagged structural equation temporal path models adjusting for cardiometabolic and lifestyle factors. RESULTS: Over follow-up, the prevalence of elevated systolic BP/hypertension increased from 6.4% to 12.2%, LVH from 3.6% to 7.2%, and LVDD from 11.1% to 16.3%. Cumulative elevated systolic BP/hypertension was associated with worsening LVH in female participants (OR 1.61, CI 1.43-1.80 P < .001) but not in male participants. Elevated systolic BP/hypertension was associated with worsening LVDD in male and female participants. Elevated diastolic BP/hypertension was associated with worsening LVH in male and female participants. In cross-lagged temporal path models, higher baseline systolic BP was associated with LVDF (ß = 0.09, SE = 0.002, P = .029) but not LVMI2.7 at follow-up. Higher baseline cardiac indices were not associated with follow-up systolic BP. Higher baseline diastolic BP was associated with follow-up higher cardiac indices except LVDF. Baseline LVMI2.7 was not associated with follow-up diastolic BP. CONCLUSIONS: Elevated BP/hypertension may temporally precede premature cardiac damage in youth.

Diagnóstico ecocardiográfico de hipertrofia ventricular izquierda en población pediátrica según método de normalización de masa ventricular e impacto del estado nutricional / Echocardiographic diagnosis of left ventricular hypertrophy in children according to the ventricular mass normalization method and impact of nutritional status

Antecedentes: la presencia de hipertrofia ventricular izquierda (HVI) es un marcador pronóstico y de severidad en condiciones de sobrecarga de presión. Se determina por masa ventricular (MV) aumentada en el ecocardiograma, debiéndose ajustar la MV por tamaño corporal en pediatría (normalización). Existen múltiples métodos de normalización, pero se desconoce si estos métodos son comparables. Objetivo: comparar distintos métodos de normalización de MV en sujetos con y sin sobrecarga de presión y evaluar el impacto del estado nutricional en el diagnóstico de HVI. Métodos: estudio de corte transversal en niños entre 5-18 años, divididos en 3 grupos: A) sin sobrecarga de presión (SSP), B) HTA (confirmado o sospecha), o C) Con cardiopatía obstructiva izquierda (CCOI, gradiente ≥25 mmHg). Se analizó antropometría, presión arterial y parámetros ecocardiográficos convencionales. Se determinó HVI por 4 mé-todos de normalización de MV: 1) Superficie corporal (SC) según sexo, 2) Talla2,7>51g/m2,7 3) Z-Score de Talla ≥ Z+2 y 4) Masa corporal magra ≥ Z+2. Se evaluó la concordancia de los métodos por grupo y según el diagnóstico nutricional. Resultados: se analizaron 1162 sujetos, 673(57,9%) hombres, edad 10,2 ± 3,2 años, 852(73,3%) SSP, 192(16,5%) con HTA y 118(10,2%) con CCOI. Un 38,6% presentaba malnutrición por exceso. Se observó diferencia entre los métodos para HVI en pacientes SSP y con CCOI(p=0,01), y en obesos con CCOI. La concordancia entre los métodos fue variable (rango de Kappa 0,38­0,71). Conclusiones: existe variabilidad y discrepancia entre los distintos métodos de normalización utilizados para definir HVI, influenciados por el estado nutricional.

Background: The presence of left ventricular hypertrophy (LVH) is both prognostic and severity marker in pressure overload conditions. It is determined by increased ventricular mass (MV) in the echocardiogram. MV must be adjusted for body size in pediatrics (normali-zation). There are multiple normalization methods, but it is unknown whether these methods are comparable. Objective: To compare different methods of MV normalization in subjects with and without pressure overload and to evaluate the impact of nutritional status on LVH diagnosis. Methods: Cross-sectional study in children aged 5-18 years, divided into 3 groups: A) without pressure overload (SSP), B) Systemic hypertension (confirmed or suspected), or C) Left obstructive heart disease (CCOI, gradient ≥ 25mmHg). Anthropometrics, blood pressure, and conventional echocardiographic parameters were analyzed. LVH was determined by 4 MV normalization methods: 1) Body surface area (BSA) adjusted by gender, 2) height2.7, 3) Z-Score height ≥ Z+2, and 4) lean body mass ≥ Z+2. The concordance of the methods was evaluated by group and according to the nutritional diagnosis. Results: 1162 subjects were analyzed, 673(57.9%) men, age 10.2 ± 3.2 years, 852(73.3%) SSP, 192(16.5%) with hypertension and 118(10.2%) with CCOI. 38.6% presented overnutrition. A difference was demonstrated between the methods for LVH diagnosis in patients with SSP and with CCOI (p=0.01), and in obese patients with CCOI. Agreement between methods was variable (Kappa range 0.38­0.71). Conclusions: There is variability and discrepancy between the different normalization methods used to define LVH, influenced by nutritional status.

Caracterización de la hipertensión arterial en adultos menores de 30 años de edad de un hospital del Paraguay

RESUMEN Introducción: la hipertensión arterial constituye el principal factor de riesgo para el desarrollo de enfermedades cardiovasculares. Su detección en adultos jóvenes obliga a buscar una causa secundaria y potencialmente corregible. Objetivo: determinar las características clínicas de la hipertensión arterial en adultos menores de 30 años de edad que acuden al Hospital Nacional, Itauguá, Paraguay, en el periodo 2019-2021. Sujetos y métodos: estudio descriptivo observacional retrospectivo de corte transversal donde se incluyó 50 pacientes entre 18 y 30 años de edad con hipertensión arterial. La investigación fue aprobada por el Comité de Ética de la Universidad Nacional de Itapúa, Paraguay. Resultados: la edad media fue 23 ± 4 años, en su mayoría eran provenientes de la zona urbana, siendo 58% del sexo masculino y con un bajo nivel educativo. La media de índice de masa corporal fue 23,5 ± 5 k/m2 y 58% no tenía antecedente familiar de hipertensión arterial. La media de cifras de presión arterial fueron 150 mmHg para la sistólica y 100 mmHg para la diastólica. La hipertensión arterial secundaria se detectó en 86% de la muestra. La etiología más frecuente fue la enfermedad renal parenquimatosa (86%), de los cuales 89% padecía enfermedad renal crónica y nefritis lúpica. La frecuencia de daño de órgano blanco fue de 86%, el fondo de ojo era anormal en 8%, 46% tenía hipertrofia ventricular izquierda por electrocardiograma y 58% por ecocardiograma, 78% tenía alteración de la arquitectura normal renal por ecografía, 57% presentaba creatininemia elevada, 76% trazas de proteínas en orina tomada al azar y 80% proteinuria de 24 hs elevada. Conclusión: la forma prevalente de hipertensión arterial en los adultos jóvenes estudiados fue la secundaria, con leve predominio del sexo masculino, con normopeso y sin antecedente familiar. La principal causa fue la enfermedad renal parenquimatosa. Más de la mitad de los casos presentó hipertrofia ventricular izquierda y proteinuria elevada.

ABSTRACT Introduction: High blood pressure is the main risk factor for the development of cardiovascular diseases. Its detection in young adults makes necessary to look for a secondary and potentially correctable cause. Objective: To determine the clinical characteristics of arterial hypertension in adults under 30 years of age who attended the Hospital Nacional of Itauguá, Paraguay, in the period 2019-2021. Subjects and methods: Retrospective observational cross-sectional descriptive study which included 50 patients between 18 and 30 years of age with arterial hypertension. The research was approved by the Ethics Committee of the National University of Itapúa, Paraguay. Results: The mean age was 23±4 years, most patients were from urban areas, 58% was male and had a low educational level. The mean body mass index was 23.5±5 k/m2 and 58% had no family history of arterial hypertension. The mean blood pressure values were 150 mmHg for systolic and 100 mmHg for diastolic. Secondary arterial hypertension was detected in 86% of the sample. The most frequent etiology was parenchymal kidney disease (86%), of which 89% had chronic kidney disease and lupus nephritis. The frequency of target organ damage was 86%, the eye fundus was abnormal in 8%, 46% had left ventricular hypertrophy by electrocardiogram and 58% by echocardiogram, 78% had abnormal renal architecture by ultrasound, 57% had elevated creatininemia, 76% trace protein in randomly collected urine, and 80% elevated 24-hour proteinuria. Conclusion: The prevalent form of arterial hypertension in the young adults studied was secondary, with a slight predominance of males, with normal weight and without family history. The main cause was renal parenchymal disease. More than half of the cases presented left ventricular hypertrophy and high proteinuria.

The impact of mTOR inhibitors in the regression of left ventricular hypertrophy in elderly kidney transplant recipients.

End-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (≥60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n = 53) or mycophenolate sodium/regularTacrolimus (MPS group, n = 47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65±3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P = .34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P = 1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both.

Relationship Between Circulating MicroRNAs and Left Ventricular Hypertrophy in Hypertensive Patients.

Objective: Left ventricular hypertrophy (LVH) is a common complication of hypertension and microRNAs (miRNAs) are considered to play an important role in cardiac hypertrophy development. This study evaluated the relationship between circulating miRNAs and LVH in hypertensive patients. Methods: Two cohorts [exploratory (n = 42) and validation (n = 297)] of hypertensive patients were evaluated by clinical, laboratory and echocardiography analysis. The serum expression of 754 miRNAs in the exploratory cohort and 6 miRNAs in the validation cohort was evaluated by the TaqMan OpenArray® system and quantitative polymerase chain reaction, respectively. Results: Among the 754 analyzed miRNAs, ten miRNAs (miR-30a-5p, miR-let7c, miR-92a, miR-451, miR-145-5p, miR-185, miR-338, miR-296, miR-375, and miR-10) had differential expression between individuals with and without LVH in the exploratory cohort. Results of multivariable regression analysis adjusted for confounding variables showed that three miRNAs (miR-145-5p, miR-451, and miR-let7c) were independently associated with LVH and left ventricular mass index in the validation cohort. Functional enrichment analysis demonstrated that these three miRNAs can regulate various genes and pathways related to cardiac remodeling. Furthermore, in vitro experiments using cardiac myocytes demonstrated that miR-145-5p mimic transfection up-regulated the expression of brain and atrial natriuretic peptide genes, which are markers of cardiac hypertrophy, while anti-miR-145-5p transfection abrogated the expression of these genes in response to norepinephrine stimulus. Conclusions: Our data demonstrated that circulating levels of several miRNAs, in particular miR-145-5p, miR-451, and let7c, were associated with LVH in hypertensive patients, indicating that these miRNAS may be potential circulating biomarkers or involved in hypertension-induced LV remodeling.

Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism.

BACKGROUND: The estimation of left ventricular ejection fraction (LVEF) by 2D echocardiography (2D-ECHO) is the most used tool to assess LV systolic function (LVSF). Global longitudinal strain (GLS) has recently been suggested as a superior method for several evaluations. This study explored the association and prevalence of LV systolic dysfunction (LVSD) by using these methods in patients with end-stage renal disease (ESRD) and severe hyperparathyroidism (SHPTH); both associated with cardiovascular events (CEs). AIM: To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional 2D-ECHO. METHODS: In 62 patients with ESRD and SHPTH, asymptomatic, and without a history of CEs, LVSF was evaluated by 2D-ECHO, obtaining the EF, by the Simpson biplane method, and GLS by speckle tracking. RESULTS: The total patients with ESRD had a preserved LVEF (> 50%) but abnormal GLS (< 13.55%). Additionally, multivariate analysis showed an independent association of GLS and serum parathyroid hormone (PTH), LV mass index, and hemoglobin. Also, PTH was independently associated with lateral e' wave and tricuspid regurgitation velocity. CONCLUSION: In patients with SHPTH linked to ESRD, the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.

Sildenafil prevents right ventricular hypertrophy and improves heart rate variability in rats with pulmonary hypertension secondary to experimental diabetes.

Chronic treatment with sildenafil (SILD) is an effective protector on the development of cardiovascular complications of pulmonary hypertension (PH) and diabetes. However, to date, no studies have evaluated the effect of SILD on cardiopulmonary pathophysiology during PH secondary to type 1 diabetes. AIM: The present study aimed to evaluate the beneficial effects of chronic SILD treatment on pulmonary arterial pressure, right ventricular hypertrophy (RVH) and cardiac autonomic dysfunction in rats with PH secondary to diabetes. METODOLOGY: Male Sprague Dawley rats were randomly distributed into the control group (saline), diabetic group (60 mg/kg with streptozotocin), SILD-treated control group (20 mg/kg) and SILD-treated diabetic group. RESULTS: After 8 weeks the type 1 diabetic animals presented PH, endothelial dysfunction of the pulmonary arteries, electrocardiographic alterations, RVH and overexpression of phosphodiesterase type 5 in the heart. In type 1 diabetic animals, SILD treatment prevented the development of PH, endothelial dysfunction and RVH. SILD treatment also prevented alterations in the corrected QT period and heart rate variability and prevented overexpression of phosphodiesterase type 5. CONCLUSION: Our results indicate for the first time that SILD treatment prevents pulmonary arterial endothelial dysfunction, pulmonary hypertension, right ventricular hypertrophy and improves heart rate variability in type 1 diabetic rats.