[Pheochromocytoma as a simulator of cardiac pathology]. / Feocromocitoma como simulador de patología cardiaca.

Pheochromocytomas are rare neuroendocrine tumors that can present as hypertensive crises or serious cardiac and cerebrovascular complications that endanger the patient's life. Two unusual cases of adrenergic crises induced by pheochromocytoma with cardiovascular manifestations are presented, one with multiple complications/multiorgan failure, fatal outcome and definitive diagnosis in the post mortem autopsy, and another with a satisfactory evolution after diagnosis and appropriate treatment.

Terapia génica para la insuficiencia cardiaca y las miocardiopatías / Gene therapy for heart failure and cardiomyopathies

Las estrategias de terapia génica incluyen diversos enfoques, como la sustitución y la edición de genes. La sustitución proporciona una copia funcional de un gen alterado y la edición permite corregir una mutación genética preexistente. La terapia génica ya está aprobada para trastornos genéticos como la amaurosis congénita de Leber y la atrofia muscular espinal, y actualmente se estudia su uso en cardiología. En esta revisión se resume el mecanismo de las distintas estrategias de terapia génica, los sistemas de administración disponibles, los principales riesgos relacionados con la terapia génica, los ensayos clínicos en curso y los objetivos futuros, con especial atención a las miocardiopatías.(AU)

Gene therapy strategies encompass a range of approaches, including gene replacement and gene editing. Gene replacement involves providing a functional copy of a modified gene, while gene editing allows for the correction of existing genetic mutations. Gene therapy has already received approval for treating genetic disorders like Leber's congenital amaurosis and spinal muscular atrophy. Currently, research is being conducted to explore its potential use in cardiology. This review aims to summarize the mechanisms behind different gene therapy strategies, the available delivery systems, the primary risks associated with gene therapy, ongoing clinical trials, and future targets, with a particular emphasis on cardiomyopathies.(AU)

Gene therapy for heart failure and cardiomyopathies.

Gene therapy strategies encompass a range of approaches, including gene replacement and gene editing. Gene replacement involves providing a functional copy of a modified gene, while gene editing allows for the correction of existing genetic mutations. Gene therapy has already received approval for treating genetic disorders like Leber's congenital amaurosis and spinal muscular atrophy. Currently, research is being conducted to explore its potential use in cardiology. This review aims to summarize the mechanisms behind different gene therapy strategies, the available delivery systems, the primary risks associated with gene therapy, ongoing clinical trials, and future targets, with a particular emphasis on cardiomyopathies.

Registro Nacional Argentino de Resonancia Cardíaca (RENAREC) / Argentine National Cardiac Magnetic Resonance Imaging Registry (RENAREC)

RESUMEN Introducción: La utilidad de la resonancia magnética cardíaca (RMC) ha crecido ampliamente en los últimos años, en los cuales se han publicado distintos registros internacionales sobre su uso e impacto clínico. Sin embargo, no contamos con este tipo de información en Argentina. Objetivo: Evaluar indicaciones, protocolos utilizados, seguridad y consecuencias terapéuticas de la RMC en la República Argentina. Material y métodos: Se diseñó un registro prospectivo a nivel nacional con recolección de datos demográficos, indicaciones de RMC, complicaciones asociadas, diagnósticos y consecuencias terapéuticas. Resultados: Participaron 34 centros de 10 provincias de Argentina (85% centros privados, 59% centros con internación). Se incluyeron 1131 pacientes (edad 54 ± 18 años, 61% varones). Las principales indicaciones para el estudio de RMC fueron la miocardiopatía hipertrófica (13,9%) y la arritmia ventricular (12,3%). El 99,7% de los estudios fueron reportados sin complicaciones. Los resultados más frecuentes de la RMC fueron: normal (31,2%), miocardiopatía no isquémica (14,7%), miocardiopatía isquémico-necrótica (11,6%) y miocardiopatía hipertrófica (8,9%). La sospecha clínica fue confirmada en el 23,6% de los casos y la RMC generó un diagnóstico nuevo no sospechado en el 48,7% de los casos. Las consecuencias terapéuticas más frecuentes fueron el alta hospitalaria (31,6%) seguida por el cambio en la medicación (28,1%). Conclusiones: La RMC es un estudio ampliamente utilizado en Argentina, principalmente en centros privados, con un número muy bajo de complicaciones. Las principales indicaciones son las miocardiopatías (hipertrófica y dilatada) y la arritmia ventricular, y provee un diagnóstico nuevo no sospechado en casi la mitad de los casos. Se requieren de otros estudios en el futuro para evaluar las implicancias clínicas y terapéuticas.

ABSTRACT Background: The usefulness of cardiac magnetic resonance imaging (MRI) has greatly increased in the last years. Different international registries have been published on its use; however, there is no data available from Argentina. Objective: The aim of this study was to evaluate different indications, protocols, safety and therapeutic consequences of cardiac MRI in Argentina. Methods: A prospective national registry was designed with collection of demographic data, indications for cardiac MRI, associated complications, diagnoses and therapeutic consequences. Results: A total of 34 centers from 10 provinces of Argentina (85% private and 59% with inpatient capacity) participated in the study, including 1131 patients (mean age 54±18 years and 61% males). The main indications for cardiac MRI were hypertrophic cardiomyopathy (13.9%), and ventricular arrhythmia (12.3%). In 99.7% of cases, no study complications were reported. The most frequent results of cardiac MRI were: normal (31.2%), non-ischemic cardiomyopathy (14.7%), ischemic-necrotic cardiomyopathy (11.6%) and hypertrophic cardiomyopathy (8.9%). Clinical suspicion was confirmed in 23.6% of cases and cardiac MRI generated an unsuspected new diagnosis in 48.7% of cases. The main therapeutic consequences were hospital discharge (31.6%) followed by change in medication (28.1%). Conclusions: Cardiac MRI is widely used in Argentina, mainly in private centers with a very low incidence of complications. Cardiomyopathies (hypertrophic and dilated) and ventricular arrhythmia are its main indication, and it provides a new unsuspected diagnosis in almost half of the cases. Further studies are required to assess its clinical and therapeutic impact.

Hypertrophic cardiomyopathy. Proposal for a new classification / Miocardiopatía hipertrófica. Propuesta de una nueva clasificación

Abstract Hypertrophic cardiomyopathy (HCM) is a clinical condition, but its name has been subjected to frequent changes over the years, largely because of its morphological and functional heterogeneity, which leads the clinician who is focused on its study to have difficulty in understanding how to diagnose it and when and how to treat it. Regarding its name, it has been called in more than 75 different ways, and it has being classified with difficulty through echocardiography for more than 40 years. Today, it is necessary to understand that the diverse phenotypic behavior, as well as the evolutionary stages of the disease, must be approached in a practical and effective way, so that it easier to understand its clinical behavior and prognosis, as well as the therapeutic needs in each particular case. We review the aspects related to the name of the condition and propose a new classification that could provide the clinical and surgical cardiologist a better understanding of HCM in its various morphological and functional aspects.

Resumen La Miocardiopatía Hipertrófica es una entidad clínica que ha sido sometida durante años a cambios frecuentes en su denominación, en gran parte consecuencia de su heterogeneidad morfológica y funcional, lo que hace que el clínico enfocado a su estudio, tenga dificultad en el entendimiento de cómo hacer el diagnóstico y cuándo y cómo tratarle. Nominativamente ha sido llamada de más de 75 formas diferentes y clasificada con dificultad mediante ecocardiografía hace ya más de 40 años. Hoy en día es necesario entender que su comportamiento fenotípico diverso así como las etapas evolutivas de la enfermedad, deben ser abordadas de una forma práctica y eficaz, de tal forma que ello facilite el entendimiento de su comportamiento clínico y su pronóstico, así como de las necesidades terapéuticas en cada caso en particular. Se hace una revisión de los aspectos nominativos de la entidad y proponemos una nueva clasificación que podría facilitar al cardiólogo clínico y quirúrgico un mejor entendimiento de la Miocardiopatía Hipertrófica en sus diversas formas morfológicas y funcionales.

Hypertrophic cardiomyopathy. Proposal for a new classification.

Hypertrophic cardiomyopathy (HCM) is a clinical condition, but its name has been subjected to frequent changes over the years, largely because of its morphological and functional heterogeneity, which leads the clinician who is focused on its study to have difficulty in understanding how to diagnose it and when and how to treat it. Regarding its name, it has been called in more than 75 different ways, and it has being classified with difficulty through echocardiography for more than 40 years. Today, it is necessary to understand that the diverse phenotypic behavior, as well as the evolutionary stages of the disease, must be approached in a practical and effective way, so that it easier to understand its clinical behavior and prognosis, as well as the therapeutic needs in each particular case. We review the aspects related to the name of the condition and propose a new classification that could provide the clinical and surgical cardiologist a better understanding of HCM in its various morphological and functional aspects.

La Miocardiopatía Hipertrófica es una entidad clínica que ha sido sometida durante años a cambios frecuentes en su denominación, en gran parte consecuencia de su heterogeneidad morfológica y funcional, lo que hace que el clínico enfocado a su estudio, tenga dificultad en el entendimiento de cómo hacer el diagnóstico y cuándo y cómo tratarle. Nominativamente ha sido llamada de más de 75 formas diferentes y clasificada con dificultad mediante ecocardiografía hace ya más de 40 años. Hoy en día es necesario entender que su comportamiento fenotípico diverso así como las etapas evolutivas de la enfermedad, deben ser abordadas de una forma práctica y eficaz, de tal forma que ello facilite el entendimiento de su comportamiento clínico y su pronóstico, así como de las necesidades terapéuticas en cada caso en particular. Se hace una revisión de los aspectos nominativos de la entidad y proponemos una nueva clasificación que podría facilitar al cardiólogo clínico y quirúrgico un mejor entendimiento de la Miocardiopatía Hipertrófica en sus diversas formas morfológicas y funcionales.

Cardiodesfibrilador implantable: estado del arte / Cardiac defibrillators: state of the art

Resumen La muerte súbita cardiaca es una consecuencia devastadora de las enfermedades estructurales del corazón y un problema de salud pública en todo el mundo; es responsable de alrededor del 50% de las muertes por causa cardiovascular. Su incidencia es mayor en personas por encima de los de 40 años, siendo en esta población la cardiopatía isquémica instaurada o durante la fase aguda del infarto al miocardio los factores de riesgo más importantes; sin embargo, hay otros factores no relacionados con isquemia, como la cardiomiopatía dilatada, hipertrófica o valvular. La fibrilación y la taquicardia ventricular son la causa más frecuente de muerte súbita cardiaca en adultos. Los cardiodesfibriladores implantables son ampliamente utilizados y recomendados por las sociedades de cardiología para la prevención primaria y secundaria de la muerte súbita cardiaca.

Abstract Sudden cardiac death is a devastating consequence of structural heart disease and a global public health problem, accounting for close to 50% of cardiovascular deaths. Its incidence is greater in people over the age of 40, with the most important risk factors being: established ischemic heart disease or ischemia during the acute phase of a myocardial infarction. However, there are other factors, unrelated to ischemia, such as dilated, hypertrophic, or valvular cardiomyopathy. Ventricular fibrillation and tachycardia are the most frequent causes of sudden cardiac death in adults. Implantable cardioverter-defibrillators are widely used and recommended by cardiology societies for primary and secondary prevention of sudden cardiac death.

Muerte súbita de jóvenes: rendimiento diagnóstico de un programa autonómico de autopsia molecular con secuenciación masiva / Sudden cardiac death in persons aged 50 years or younger: diagnostic yield of a regional molecular autopsy program using massive sequencing

Introducción y objetivos La muerte súbita (MS) de personas jóvenes suele tener una causa genética, por lo cual la «autopsia molecular» puede tener implicaciones importantes para los familiares. El objetivo del estudio es evaluar el rendimiento diagnóstico de un programa de autopsia molecular mediante secuenciación masiva. Métodos Estudio prospectivo de una cohorte de pacientes consecutivos de edad ≤ 50 años y fallecidos por MS no violenta, a los que se realizó autopsia molecular mediante paneles amplios por secuenciación masiva, con posterior cribado familiar clínico y genético. Se analizan datos demográficos, clínicos, toxicológicos y genéticos. Resultados Se estudiaron 123 casos consecutivos de MS a edades ≤ 50 años. La incidencia de MS fue de 5,8 casos/100.000 individuos/año, a una media de edad de 36,15±12,7 años; 95 (77%) eran varones. La causa fue cardiaca en el 53%; MS inexplicada en el 24%, tóxicos en el 10,6% y MS del lactante en el 4%. De las cardiacas, el 38% por cardiopatía isquémica, el 7% por miocardiopatía arritmogénica, el 5% por miocardiopatía hipertrófica y el 11% por hipertrofia ventricular izquierda idiopática. Se indicó análisis genético en 62 casos (50,4%). Se hallaron variantes genéticas en 42 (67,7%), con una media de 3,4±4 variantes/paciente, que se consideraron patogénicas o probablemente patogénicas en el 30,6%. De las MS inexplicadas, hasta el 70% presentó alguna variante genética. El estudio familiar permitió detectar a 21 portadores o afectos, 5 de ellos estaban en riesgo, por lo que se indicó implante de desfibrilador. Conclusiones El estudio protocolizado y exhaustivo de la MS cardiaca de personas jóvenes es factible y necesario. En un alto porcentaje la causa es genética y, por lo tanto, existen familiares en riesgo que pueden beneficiarse de un diagnóstico y un tratamiento precoces para evitar complicaciones. (AU)

Introduction and objectives Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of “molecular autopsy” may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. Methods We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. Results We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. Conclusions Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications. (AU)

Impact of the creation of specialized units for patients with hypertrophic cardiomyopathy.

INTRODUCTION AND OBJECTIVES: According to current international guidelines, hypertrophic cardiomyopathy (HCM) patients should be managed in specialized units. However, there is lack of data on the impact of the creation of these units in the management of HCM patients. Our goal was to assess the impact of the creation of an Inherited Inherited Diseases Cardiac Unit (ICDU) in the current management of patients with HCM. METHODS: We analyzed 114 consecutive patients (62.6±8 years old, 70.2% males) with HCM. Variables related to optimal management of HCM patients and their family study were recorded, as well as guidance on the risk of sudden death. We analyzed whether patients were assessed by the ICDU or at a general cardiology consultation (GCC). RESULTS: 50 patients were assessed in the IDCU and 64 in the GCC. Familial screening was more frequent in patients assessed by the IDCU (45.3% vs. 4%; p<0.01), requesting more genetic studies of the index case (70.3% vs. 14%; p<0.01) and cardiac magnetic resonance (53.1% vs. 18%; p<0.01). Sudden death risk score was performed more frequently in patients after the creation of an IDCU (67.2% vs. 28%; p<0.01). Treatment with beta-blockers was similar in both groups (72% vs. 78.1%; p=0.24). An implantable cardiac defibrillator was indicated similarly in both groups (12.5% in ICDU and 6% in GC; p=0.24). CONCLUSIONS: The implementation of an IDCU improved the quality of the medical care for HCM patients by performing a better study of the patients and their families.

Sudden cardiac death in persons aged 50 years or younger: diagnostic yield of a regional molecular autopsy program using massive sequencing.

INTRODUCTION AND OBJECTIVES: Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of "molecular autopsy" may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. METHODS: We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. RESULTS: We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. CONCLUSIONS: Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.

Miocardiopatía dilatada en el niño / Dilated cardiomyopathy in children

Las miocardiopatías (MC) son enfermedades del músculo cardíaco infrecuentes, con una incidencia anual de 1.1-1.2 casos por 100.000 niños. La miocardiopatía dilatada (MCD) es la principal forma, se caracteriza por dilatación ventricular y disfunción sistólica, y es causa importante de insuficiencia cardíaca congestiva (ICC). Las etiologías en niños son múltiples, siendo idiopáticas en el 50%-70%. En la evaluación de un niño con MCD es fundamental descartar causas secundarias potencialmente reversibles. El ecocardiograma es la principal herramienta diagnóstica: permite establecer el fenoti po cardíaco, grado de compromiso funcional, y la evolución y respuesta al tratamiento médico. El pronóstico es limitado, siendo mejor en pacientes menores a 1 año al momento de presentación, post miocarditis, o con menor grado de disfunción sistólica ventricular. En los primeros 2 años post presentación alrededor de 20% tienen normalización de la función ventricular; 40%-50% fallece o requiere un trasplante cardíaco (TC) en los primeros 5 años. El tratamiento médico se basa en recomendaciones de adultos, siendo la evidencia pediátrica muy limitada. El TC es la terapia definitiva en pacientes con ICC terminal, con excelentes resultados a corto y mediano plazo. Una proporción importante de pacientes requiere estabilización en lista de espera, incluyendo asistencia mecánica circulatoria como puente a trasplante. El objetivo de este artículo es actualizar la información dis ponible en etiología, mecanismos fisiopatológicos, factores pronósticos, y tratamiento de la MCD en niños.

Pediatric cardiomyopathies are infrequent diseases of the cardiac muscle, with an annual inciden ce of 1.1 to 1.2 per 100,000 children. Dilated cardiomyopathy (DCM) is the predominant form, characterized by ventricular dilatation and systolic dysfunction. Etiologies are multiple, with at least 50%-70% of cases being idiopathic. When assessing a child with DCM, secondary potentially reversible causes must be ruled out. The main diagnostic tool is the echocardiogram which allows the identification of cardiac phenotype, to establish the degree of functional compromise, and res ponse to medical therapy. Prognosis is limited but more favorable in infants younger than 1 year at the onset, post myocarditis, or with a lesser degree of ventricular dysfunction. At least 20% of patients may recover ventricular function in the first 2 years after the onset and 40%-50% may die or need heart transplant in the first 5 years. Medical therapy is mainly based on adult experience with limited scientific evidence in children. Heart transplant is the therapy of choice in patients with end-stage disease, with excellent short- and medium-term survival. A significant proportion of patients may require stabilization on the waiting list, including the use of mechanical circulatory support as a bridge to transplantation. The purpose of this revision is to update the available infor mation on etiology, physiopathological mechanisms, prognostic factors, and management of DCM in children.

Evolución a mediano plazo de pacientes con diagnóstico de cardiopatía amiloidótica por transtiretina / Mid-term Outcome of Patients with Diagnosis of Transthyretin Cardiac Amyloidosis

RESUMEN Introducción: El compromiso cardíaco es la principal causa de morbimortalidad en la amiloidosis, independientemente de la patogenia productora del amiloide subyacente. La amiloidosis por transtiretina (TTR) es una de las variantes más frecuentes, por lo cual el objetivo de este trabajo fue evaluar las características de una cohorte de pacientes con diagnóstico de cardiopatía amiloidótica por TTR (CA-TTR) Material y métodos: Se recabaron datos de los estudios basales, de la metodología diagnóstica y de la evolución de 49 pacientes en seguimiento en la Clínica de Miocardiopatías de nuestra institución. Resultados: La mediana del tiempo de seguimiento fue de 1258 días (410-2004) y la edad promedio de 79 ± 9 años. Al inicio del seguimiento, el 57% de los pacientes estaban en clase funcional I, el 26%, en II y el 16%, en III-IV. El diagnóstico se basó en centellograma con difosfonatos en el 92%; en el 24% requirió biopsia. La mortalidad global fue del 19%, con 15% de muerte cardiovascular. La tasa de internación por insuficiencia cardíaca fue 29%; el 63% de los pacientes empeoró su clase funcional. Conclusiones: El seguimiento de nuestros pacientes con CA-TTR expresa los cambios que ha sufrido el proceso diagnóstico, con una reducción de estudios invasivos y tiempo para la caracterización. El diagnóstico de pacientes en etapas "tempranas" de la enfermedad parece impactar en los resultados a mediano plazo.

ABSTRACT Background: Cardiac involvement is the main cause of morbidity and mortality in amyloidosis, regardless of the underlying pathogenesis of amyloid production, and transthyretin (TTR) amyloidosis is one of the most frequent variants. Objective: The aim of this study was thus to assess the characteristics of a cohort of patients with diagnosis of TTR cardiac amyloidosis (ATTR-CA). Methods: Baseline data and diagnostic and follow-up methodology were collected from 49 patients treated at the cardiomy-opathy clinic of our institution. Results: Median follow-up was 1,258 days (410-2004). Mean age was 79±9 years, and 57% of patients were in functional class (FC) I, 26% in FC II and 16% in FC III-IV at follow-up onset. Diagnosis was made with diphosphonate scintigraphy in 92% of patients and 24% required a biopsy. Overall mortality was 19%, with 15% of cardiovascular death. The rate of hospitalization for heart failure was 29% and 63% of patients worsened their FC. Conclusions: Follow-up of patients with ATTR-CA expresses the changes undergone by the diagnostic process, with a reduction of invasive studies and time to characterization. The diagnosis of patients at "early stages of the disease" seems to have an impact on mid-term outcomes.

Compromiso cardiovascular en COVID-19 / Cardiovascular involvement in COVID-19

El compromiso cardiovascular de los pacientes con COVID-19, especialmente en la subpoblación con factores de riesgo cardiovasculares, se asocia a la severidad de la enfermedad e inclusive a una mayor mortalidad en algunas series de casos. Los mecanismos fisiopatológicos descritos con mayor claridad son la injuria miocárdica directa y el proceso asociado a la inflamación sistémica.Las manifestaciones cardiovasculares son diversas e incluyen injuria miocárdica, miocarditis, miocardiopatías, insuficiencia cardíaca, síndromes coronarios agudos, arritmias, eventos tromboembólicos. Adicionalmente, debemos considerar los efectos adversos de los medicamentos utilizados para tratar la infección viral. (AU)

Cardiovascular compromise among COVID-19 patients, especially in the subpopulation with cardiovascular risk factors, is associated with severity of disease and a higher mortality in some case-series. The most clearly described pathophysiological mechanisms are direct myocardial injury and the process associated with systemic inflammation. Cardiovascular manifestations are diverse and include myocardial injury, myocarditis, cardiomyopathies, heart failure, acute coronary syndromes, arrhythmias, thromboembolic events. Moreover, we must consider the adverse effects of medications used to treat the viral infection. (AU)

Enfermedad de Pompe infantil: Diagnóstico y tratamiento / Infantile-onset Pompe disease: Diagnosis and management

La enfermedad de Pompe, o deficiencia de maltasa ácida o glucogenosis tipo II, es una grave enfermedad genética, autosómica recesiva, progresiva, poco frecuente, causada por la deficiencia en la enzima alfa glucosidasa. En la edad pediátrica, puede presentarse con la "forma clásica", la más conocida, con grave compromiso cardíaco y franca hipotonía, o con la "forma no clásica", con comienzo temprano del compromiso motor. La "forma de comienzo tardío" del adulto también puede ocurrir en la infancia o en la adolescencia. Se actualizan los hallazgos clínicos y de diagnóstico disponibles, ya que un tratamiento temprano con reemplazo de la enzima faltante puede mejorar la supervivencia y la calidad de vida del paciente. Se revisan los beneficios y los efectos adversos del tratamiento disponible y nuevas líneas de investigación terapéutica.

Pompe disease, also known as acid maltase deficiency or glycogenosis type II, is a rare severe, autosomal, recessive, and progressive genetic disorder caused by deficiency in alpha-glucosidase. The classic infantile-onset is the most broadly known form of Pompe disease, which presents with severe heart involvement and clear hypotonia, while the non-classic presentation occurs with early motor involvement. Late-onset Pompe disease develops in adults, but it may also occur during childhood or adolescence. Here we update the available clinical and diagnostic findings because an early management with enzyme replacement therapy may improve patients' survival and quality of life. We also review the benefits and adverse effects of available treatments and new lines of therapeutic research.

Evolution and trends in a pediatric cardiac magnetic resonance imaging program in a tertiary hospital over a 14-year period. / Evolución y tendencias de un programa de resonancia magnética cardiaca pediátrica en un hospital terciario durante 14 años.

OBJECTIVES: 1. To review the activity in our hospital's pediatric cardiac magnetic resonance imaging (cMRI) program from its inception to the present. 2. To evaluate changes in the number of patients, in the number of studies done under anesthesia, in the number of studies done with contrast material (magnetic resonance angiography (MRA) and delayed enhancement), and in representative diseases studied. 3. To estimate trends in the parameters evaluated in objective 2. MATERIAL AND METHODS: The pediatric cMRI program at our hospital started on February 14, 2005. We assessed cMRI studies done between the inception of the program and December 31, 2018. The cases were entered in a calculation table that included sex, date of birth, date of examination, clinical presentation, radiologic diagnosis, sequences done, and anesthesia. For each year, we obtained data about patients' age, studies done under anesthesia, contrast-enhanced MRA, delayed enhancement studies, and postoperative studies. We also evaluated the evolution of the number of patients studied for a group of representative diseases (coarctation of the aorta; tetralogy of Fallot; dextro-transposition of the great arteries; corrections of univentricular heart; hypoplastic left heart syndrome; anomalous pulmonary venous return; and cardiomyopathy). We analyzed these data with bar graphs, evolutions of means, and logarithmic trend curves. RESULTS: A total of 2606 cases were included. The number of cases per year increased gradually. The mean age of all patients was 12.5 years, and the age of the patients studied also increased during the 14-year period. Anesthesia was used in 42%. Contrast-enhanced MRA was done in 57.6% and delayed enhancement in 42.13%. The most common condition was aortic coarctation (16.39%), although the frequency of aortic coarctation and hypoplastic left heart syndrome decreased slightly during the period. By contrast, the frequency of cardiomyopathy (7.25% of cases) increased slightly, to the point where it represented 9.35% in 2018. CONCLUSION: During the 14-year period in which pediatric cMRI has been done at our hospital, the conditions studied, the type of patients, and the techniques used has varied; the number of patients and patients' age has increased, where as the frequency of MRA studies has decreased. The prevalence of the different conditions studied has also changed.

Clasificación de las miocardiopatías. Un objetivo, muchas propuestas / Classification of cardiomyopathies. One goal, many proposals / Classificação das cardiomiopatias. Um objetivo, muitas propostas

Resumen: Resulta innegable la importancia de la patología del miocardio como causa de enfermedad y muerte de origen cardíaco. Actualmente, cerca de la mitad de los pacientes que fallecen súbitamente en la niñez y la adolescencia o que reciben un trasplante cardíaco están afectados por una miocardiopatía. No obstante, las enfermedades del miocardio han constituido históricamente un grupo desconcertante, tanto en relación con su origen como en su sistematización nosológica. Identificadas inicialmente con patología inflamatoria y concebidas luego como desórdenes de causa desconocida o manifestación de múltiples enfermedades sistémicas, las miocardiopatías fueron más tarde categorizadas en ciertos patrones de presentación morfológico-funcional y objeto en los últimos 30 años de intensa investigación en el ámbito de las ciencias básicas, que permitió reconocer el origen genético de muchas de estas entidades. Esa nueva información sustentó, ya en este siglo, iniciativas de clasificación por parte de la American Heart Association (AHA) y la European Society of Cardiology (ESC), que a pesar de representar un valioso avance con respecto a intentos previos, muestran áreas de incertidumbre y discrepancias sustantivas que son objeto de debate. Una propuesta más reciente, la clasificación MOGE(S), pone énfasis en la creciente información aportada por la genética molecular y en la implementación de una nosología descriptiva fenotipo-genotipo que posibilite la máxima precisión en la nomenclatura y el diagnóstico clínico. En este capítulo se revisa la evolución de los conceptos que sustentaron las sucesivas clasificaciones publicadas y se analizan las diferencias entre las propuestas de la AHA y la ESC, concluyendo en la necesidad de un abordaje conjunto del problema en pos de una nomenclatura y un ordenamiento taxonómico coherentes y universalmente compartidos.

Summary: The importance of myocardial pathology as a cause of illness and death from cardiac origin is undeniable. Currently, almost half of the patients who die suddenly in childhood and adolescence or receive a heart transplant are affected by cardiomyopathy. However, myocardial diseases have historically constituted a perplexing group, both in relation to their origin and in their nosological systematization. Initially identified with inflammatory pathology, and then conceived as disorders of unknown cause or as a manifestation of multiple systemic diseases, cardiomyopathies were later categorized in certain patterns of morphological and functional presentation, and were object in the last 30 years of intense research in the field of basic sciences, which allowed to recognize the genetic origin of many of these entities. Already in this century, that new information sustained classification initiatives by the American Heart Association (AHA) and the European Society of Cardiology (ESC), which despite being a valuable improvement over previous attempts, exhibit areas of uncertainty and substantive differences that are subject of debate. A more recent proposal, the MOGE (S) classification, stresses on the growing information provided by molecular genetics and on the implementation of a phenotype-genotype descriptive nosology that enables maximum accuracy in nomenclature and clinical diagnosis. This chapter reviews the evolution of the concepts that sustained the successive classifications published, and analyzes the discrepancies between the proposals of the AHA and the ESC, concluding on the need for a joint approach to the problem in order to generate a coherent and universally shared taxonomic arrangement and nomenclature.

Resumo: A importância da patologia miocárdica como causa de doença e morte de origem cardíaca é inegável. Atualmente, cerca de metade dos pacientes que morrem subitamente na infância e adolescência ou que recebem um transplante cardíaco são afetados pela cardiomiopatia. No entanto, historicamente, as doenças do miocárdio têm sido um grupo desconcertante, tanto em relação à sua origem quanto em sua sistematização nosológica. Inicialmente identificadas com patologia inflamatória e, em seguida concebidas como doenças de causa desconhecida ou manifestação de muitas doenças sistêmicas, as cardiomiopatias foram posteriormente categorizadas em certos padrões de apresentação morfofuncional e objeto nos últimos 30 anos de intensa investigação no campo das ciências básicas, o que permitiu reconhecer a origem genética de muitas dessas entidades. Essa nova informação sustentou, já neste século, iniciativas de classificação da American Heart Association (AHA) e da European Society of Cardiology (ESC), que apesar de representar um valioso avanço sobre as tentativas anteriores mostram áreas de incerteza e discrepâncias substanciais que são objeto de debate. Uma proposta mais recente, a classificação MOGE (S), enfatiza a crescente informação fornecida pela genética molecular e a aplicação de uma nosología descritiva fenótipo-genótipo, permitindo a maior precisão no diagnóstico clínico e nomenclatura. Neste capítulo é revista a evolução dos conceitos que sustentaram as classificações sucessivas publicadas, e as diferenças entre as propostas da AHA e da ESC são analisadas, concluindo na necessidade de um abordagem conjunto do problema em busca de uma nomenclatura e ordem taxonômica coerente e universalmente compartilhada.

Miocardiopatía inducida por arritmias / Arrhythmia-induced cardiomyopathy / Cardiomiopatia induzida por arritmia

Resumen: Los trastornos del ritmo cardíaco son una etiología frecuente y comúnmente no considerada de compromiso de la función ventricular. Pueden ser causa exclusiva o contribuyente del deterioro funcional. Las posibilidades que brinda la ablación por catéter, un recurso que logra curar definitivamente muchas arritmias, permite no solo confirmar el diagnóstico de miocardiopatía inducida por arritmia normalizando o mejorando significativamente la función ventricular, sino también modificar el pronóstico. Nos referiremos fundamentalmente a la arritmia que más frecuentemente en la clínica se asocia a disfunción ventricular: la fibrilación auricular. También analizaremos la extrasistolía ventricular cuyo rol como factor contribuyente o causante de esta patología genera habitualmente controversia.

Summary: Cardiac arrhythmias are a frequent and usually not considered etiology of ventricular dysfunction. They could be the single cause or a contributing factor of ventricular function compromise. Catheter ablation is an available resource that brings us the possibility to definitively cure several arrhythmias, confirming the diagnosis of arrhythmia induced cardiomyopathy improving or normalizing ventricular function, and in addition to modify the prognostic. We will mainly discuss atrial fibrillation, the arrhythmia more often associated in practice with heart failure. Also, we will analyze the role of premature ventricular contractions as cause or contributing factor to ventricular dysfunction, usually a controversial topic.

Resumo: Os distúrbios do ritmo cardíaco são uma etiologia comum e não são comumente considerados como comprometendo a função ventricular. Eles podem ser a causa exclusiva ou contribuinte para a deterioração funcional. As possibilidades oferecidas pela ablação por cateter, recurso que consegue curar definitivamente muitas arritmias, permitem não só confirmar o diagnóstico de cardiomiopatia induzida por arritmias normalizando ou melhorando significativamente a função ventricular, como também modificar o prognóstico. Referiremos principalmente a arritmia que mais freqüentemente está associada à disfunção ventricular, fibrilação atrial. Também analisaremos a extra-sístole ventricular cujo papel como fator contribuinte ou causador dessa patologia geralmente gera controvérsias.

Aportes de la genética al estudio y manejo clínico de las miocardiopatías / Genetic contributions to the study and clinical management of cardiomyopathies

Resumen: Las miocardiopatías son patologías muy heterogéneas asociadas a muerte súbita en jóvenes, cuyo diagnóstico y pronóstico son difíciles de establecer. El estudio genético puede ser una herramienta importante para el abordaje de estos pacientes y sus familias. Son generalmente patologías monogénicas, con penetrancia incompleta y expresividad clínica variable. Múltiples causas genéticas subyacen a la misma patología y un mismo gen puede estar asociado con fenotipos diferentes. La tecnología disponible en la actualidad permite analizar todos los genes importantes para cada fenotipo, con costos y tiempos de entrega de los resultados muy razonables. La rentabilidad del estudio genético depende de cada patología y de la probabilidad pretest de cada paciente particular. La interpretación de un estudio genético es una tarea compleja y un aspecto limitante para una correcta implementación clínica. Depende de múltiples variables y deberá ser realizado por equipos multidisciplinares con experiencia clínica en las patologías y los genes asociados. Un estudio genético positivo aportará mucha información diagnóstica y pronóstica para el paciente y su familia. Esto permitirá hacer recomendaciones en el estilo de vida, seleccionar tratamientos específicos para determinadas patologías, y decidir con más precisión el momento oportuno para implementar técnicas preventivas invasivas. Está demostrado que el screening genético en cascada luego de un resultado positivo es una estrategia costo-efectiva, que permite grandes ahorros en seguimientos clínicos innecesarios para focalizar los recursos en individuos genéticamente predispuestos.

Summary: Cardiomyopathies are heterogeneous diseases associated with sudden death in the young. The diagnosis and associated prognosis is sometimes difficult to establish. The genetic study could be an important tool for the clinical work-up of patients and families with these diseases. Cardiomyopathies are usually monogenic diseases, with incomplete penetrance and variable clinical expressivity. Several genes are associated with the same phenotype, and a particular gene could be related with different diseases. All the genes related with a particular phenotype could be study with the available sequencing technology at a reasonable price and turnaround time for the results. The yield of genetic tests depends on the type of cardiomyopathy and is specifically driven by the clinical pre-test probability of each case. The interpretation of genetic studies is complex and the main challenge for the correct clinical application of the results. Interpretation depends on several variables and should be performed by multidisciplinary teams with clinical and genetic expertise on cardiomyopathies. A positive genetic study could contribute with important diagnostic and prognostic information for the patient and the family. This information could be useful for life-style modifications, specific treatment selection and, in some cases, to decide the correct moment for primary prevention device's implantation. Cascade family screening after a positive genetic diagnosis is a cost-effective strategy for health-care systems.

Prevalencia y espectro de las enfermedades que predisponen a la muerte súbita cardiaca en niños mexicanos: una muestra obtenida del Hospital Infantil de México Federico Gómez / Prevalence and spectrum of diseases that predispose to sudden cardiac death in Mexican children: a sample obtained from The Federico Gomez Children's Hospital of Mexico

Resumen Objetivo: Determinar la prevalencia y espectro de las enfermedades que predisponen la muerte súbita cardiaca en niños mexicanos e identificar los principales signos y síntomas tempranos que pueden permitir al personal de salud sospechar acerca de estas enfermedades y referir a los pacientes a un hospital de tercer nivel de manera temprana. Métodos: La incidencia, prevalencia y prevalencia de periodo, así como los primeros síntomas, los datos clínicos y el seguimiento, se describen en todos los niños con enfermedades que predisponen a la muerte súbita cardiaca en el Hospital Infantil de México. Resultados: Cincuenta y nueve pacientes de 8 ± 5 años, 40 con miocardiopatías y 19 con enfermedades arritmogénicas hereditarias. La prevalencia del periodo fue de 9.5/1,000 pacientes/año. Los primeros síntomas más comunes fueron disnea, palpitaciones y síncope. En 9 casos se encontró un patrón de herencia mendeliana. Tres pacientes fallecieron de muerte súbita cardiaca durante el periodo de estudio. Conclusión: Las enfermedades que predisponen a la muerte súbita cardiaca en los niños no son muy conocidas por la comunidad médica y general. Todo niño con disnea, palpitaciones y/o síncope debe referirse para la búsqueda intensiva de estas enfermedades. Una evaluación cardiológica completa en todos los miembros de la familia está indicada.

Abstract Objective: To determine the prevalence and spectrum of diseases that predispose to sudden cardiac death in Mexican children, and to identify the main early signs and symptoms that can enable the health personnel to suspect these diseases and to refer the patients to a tertiary hospital in a timely manner. Methods: Incidence, prevalence, and period prevalence, as well as early symptoms, clinical data, and follow-up were recorded on all children found with diseases that predispose to sudden cardiac death in The Children's Hospital of Mexico. Results: The study included 59 patients, with a mean age of 8 ± 5 years old, with 40 cardiomyopathies, and 19 with inherited arrhythmogenic diseases. The period prevalence was 9.5/1,000 patients/year. The most common early symptoms were dyspnoea, palpitations, and syncope. A Mendelian inheritance pattern was found in 9 cases. Three patients died of sudden cardiac death during the period of the study. Conclusion: Diseases that predispose to sudden cardiac death in children are not very well known by the general medical community. Every child with dyspnoea, palpitations and/or syncope, should be referred for the intensive search of these diseases. A complete cardiological evaluation in all members of the family is indicated.

Abordaje de las cardiopatías familiares desde la Medicina genómica / Approach to familial heart diseases from Genomic Medicine

Resumen Las cardiopatías familiares son un grupo de enfermedades con alta heterogeneidad clínica y genética. Debido a que pueden heredarse y a su asociación con la muerte súbita, se recomienda efectuar un estudio clínico y genético del individuo afectado y su familia a través de una unidad especializada. Con la implementación de la secuenciación masiva se ha facilitado el acceso a los estudios genéticos en la práctica clínica de forma más rutinaria. Sin embargo, dada la gran cantidad de información obtenida se hacen necesarios el análisis y la interpretación adecuada de los resultados para garantizar un diagnóstico correcto. Este nuevo modelo de medicina amplía nuestra comprensión sobre estas patologías, gracias a que optimiza el diagnóstico, da una mejor aproximación pronóstica de los pacientes e identifica individuos asintomáticos en riesgo. Este artículo pretende realizar una revisión de la arquitectura genética de las enfermedades cardíacas hereditarias y proporcionar un enfoque práctico acerca de la utilidad de la Medicina genómica en el diagnóstico, la estratificación del riesgo y el estudio familiar en pacientes con este tipo de patologías.

Abstract The familial heart diseases are a group of diseases with high clinical and genomic heterogeneity. As they can be inherited and are associated with sudden death, it is recommended to perform a clinical and genetic study of the individual affected, as well as the family, in a specialised unit. The implementation of massive sequencing has meant that access to genetic studies is available in the most routine clinical practice. However, due to the large amount of information obtained, the results have to analysed and interpreted to ensure a correct diagnosis. This new medicine model widens the understanding of these diseases, as due to the diagnosis being optimised, it provides a more accurate prognosis for the patients, and identifies asymptomatic individuals at risk. A review is presented on the genetic architecture of heritable heart disease and provides a practical approach on the usefulness of Genomic Medicine in the diagnosis, risk stratification, and the familial study in patients with these types of heart diseases.