Pregnancy in women with dilated cardiomyopathy genetic variants.

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

Left bundle branch block-induced dilated cardiomyopathy: Definitions, pathophysiology, and therapy.

Left bundle branch block (LBBB) is a frequent finding in patients with heart failure (HF), particularly in those with dilated cardiomyopathy (DCM). LBBB has been commonly described as a consequence of DCM development. However, a total recovery of left ventricular (LV) function after cardiac resynchronization therapy (CRT), observed in patients with LBBB and DCM, has led to increasing acknowledgement of LBBB-induced dilated cardiomyopathy (LBBB-iDCM) as a specific pathological entity. Its recognition has important clinical implications, as LBBB-iDCM patients may benefit from an early CRT strategy rather than medical HF therapy only. At present, there are no definitive diagnostic criteria enabling the universal identification of LBBB-iDCM, and no defined therapeutic approach in this subgroup of patients. This review compiles the main findings about LBBB-iDCM pathophysiology and the current proposed diagnostic criteria and therapeutic approach.

Trasplante cardíaco por hemocromatosis. Caso pediátrico / Cardiac transplantation due to hemochromatosis. A pediatric case report

La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.

Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.

Efectos del tratamiento médico guiado en pacientes con miocardiopatía inducida por bloqueo de rama izquierda / Effects of guideline-directed medical therapy in patients with left bundle branch block-induced cardiomyopathy

Introducción y objetivos La miocardiopatía inducida por el bloqueo de rama izquierda (BRI) se produce en pacientes con BRI de larga duración. Es característico que muestren hiperrespuesta a las terapias de resincronización cardiaca (TRC). Sin embargo, existe poca información sobre su respuesta al tratamiento médico. El objetivo de este estudio es evaluar el cambio en la fracción de eyección del ventrículo izquierdo (FEVI) después de un periodo de 3 meses tras la dosificación del tratamiento médico recomendado por la guía de insuficiencia cardiaca. Métodos Se trata de un análisis retrospectivo, en el que se incluyó a todos los pacientes valorados en la unidad de insuficiencia cardiaca de un hospital universitario español entre 2020 y 2021, que presentaban disfunción ventricular de novo (FEVI <40%) y tenían antecedentes de BRI de larga evolución sin otras posibles causas de miocardiopatía. Resultados Se analizó a un total de 1.497 pacientes, de los que resultaron elegibles 21. El tiempo medio desde el primer diagnóstico de BRI a la primera consulta fue de 4,05±4,1 años. La FEVI media desde la primera consulta hasta el final de la dosificación mejoró del 29,5±5,7% al 32,7±8,6% (p=0,172); ninguno recuperó la función ventricular al final del seguimiento. La clase funcional de la New York Heart Association mejoró de 1,91±0,46 a 1,81±0,53 (p=0,542). Tras el implante del dispositivo de TRC en 8 pacientes, la FEVI mejoró un 18,1±6,4% (p=0,003). Conclusiones El tratamiento médico recomendado por la guía parece ser ineficaz para mejorar la FEVI y la clase funcional en pacientes con insuficiencia cardiaca de novo y miocardiopatía inducida por BRI. Basándose en la respuesta positiva a la TRC en la mejora de la FEVI, el implante temprano de TRC podría ser una estrategia razonable para estos pacientes (AU)

Introduction and objectives Left bundle branch block (LBBB)-induced cardiomyopathy occurs in patients with long-standing LBBB. These patients characteristically exhibit hyperresponsiveness to cardiac resynchronization therapies (CRT). However, there is scarce information on their response to medical treatment. The aim of this study was to assess the change in left ventricular ejection fraction (LVEF) after a 3-month period following titration of guideline-directed medical therapy for heart failure. Methods This retrospective analysis included all patients assessed in the heart failure unit of a Spanish University Hospital between 2020 and 2021, who presented with de novo ventricular dysfunction (LVEF <40%) and had a history of long-standing LBBB with no other possible causes of cardiomyopathy. Results A total of 1497 patients were analyzed, of which 21 were finally eligible. Mean time from first diagnosis of LBBB to first consultation was 4.05± 4.1 years. Mean LVEF from first consultation to end of titration improved from 29.5±5.7% to 32.7±8.6% (P = .172), but none had recovered ventricular function at the end of follow-up. New York Heart Association functional class improved from 1.91±0.46 to 1.81±0.53 (P=.542). After CRT device implantation in 8 patients, LVEF improved by 18.1±6.4% (P=.003). Conclusions Guideline-directed medical therapy seems to be ineffective in improving LVEF and functional class in patients with de novo heart failure and LBBB-induced cardiomyopathy. Based on a positive response to CRT on LVEF improvement, early CRT implantation could be a reasonable strategy for these patients (AU)

Effects of guideline-directed medical therapy in patients with left bundle branch block-induced cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Left bundle branch block (LBBB)-induced cardiomyopathy occurs in patients with long-standing LBBB. These patients characteristically exhibit hyperresponsiveness to cardiac resynchronization therapies (CRT). However, there is scarce information on their response to medical treatment. The aim of this study was to assess the change in left ventricular ejection fraction (LVEF) after a 3-month period following titration of guideline-directed medical therapy for heart failure. METHODS: This retrospective analysis included all patients assessed in the heart failure unit of a Spanish University Hospital between 2020 and 2021, who presented with de novo ventricular dysfunction (LVEF <40%) and had a history of long-standing LBBB with no other possible causes of cardiomyopathy. RESULTS: A total of 1497 patients were analyzed, of which 21 were finally eligible. Mean time from first diagnosis of LBBB to first consultation was 4.05± 4.1 years. Mean LVEF from first consultation to end of titration improved from 29.5±5.7% to 32.7±8.6% (P = .172), but none had recovered ventricular function at the end of follow-up. New York Heart Association functional class improved from 1.91±0.46 to 1.81±0.53 (P=.542). After CRT device implantation in 8 patients, LVEF improved by 18.1±6.4% (P=.003). CONCLUSIONS: Guideline-directed medical therapy seems to be ineffective in improving LVEF and functional class in patients with de novo heart failure and LBBB-induced cardiomyopathy. Based on a positive response to CRT on LVEF improvement, early CRT implantation could be a reasonable strategy for these patients.

Triptófano-5-hidroxilasa, transportador de serotonina y receptores serotoninérgicos en miocardiopatía dilatada.

BACKGROUND: Cardiomyocytes synthesize, utilize and reuptake serotonin, which is involved in the paracrine and autocrine modulation of heart activity and in the pathophysiology of some cardiovascular diseases. OBJECTIVE: To determine the expression of tryptophan-5-hydroxylase (TPH) 1 and 2, serotonin transporter protein (SERT) and serotonergic receptors in hearts with dilated cardiomyopathy (DCM) compared to controls. METHOD: A comparative study was performed in six tissue blocks of the left ventricular free wall (LVWL) and inter-ventricular septum from patients who died of DCM and six who died of no cardiovascular diseases (controls). Five slices from each block were obtained to determine the expression of TPH1 and TPH2, SERT and serotonergic receptors with antibodies specific for immunofluorescence. Immunofluorescence was analyzed by Student's t-test, accepting a significance level of p < 0.05. RESULTS: An increase in TPH1, TPH2, 5-HT2A and 5-HT2B receptors expression were observed in dilated structures compared to controls (p < 0.05). For dilated inter-ventricular septum, the 5-HT4 receptor increased its expression (p < 0.05), and SERT in PLVI compared to controls (p < 0.05). CONCLUSIONS: These results suggest that the increases observed in the expression of TPH, SERT, and serotonergic receptors in hearts with DCM compared to controls could play an important role in the pathophysiology of MCD in humans.

ANTECEDENTES: Los cardiomiocitos sintetizan, utilizan y recapturan serotonina, la cual participa en la modulación parácrina y autócrina de la actividad del corazón y en la fisiopatología de algunas enfermedades cardiovasculares. OBJETIVO: Determinar la expresión de triptófano-5-hidroxilasa (TPH) 1 y 2, transportador de serotonina (SERT) y receptores serotoninérgicos en corazones con miocardiopatía dilatada (MCD) en comparación con controles. MÉTODO: Estudio comparativo en seis bloques de la pared libre del ventrículo izquierdo (PLVI) y del septum interventricular de pacientes fallecidos por MCD y seis que murieron por enfermedades no cardiovasculares. Se obtuvieron cinco cortes de cada bloque para determinar la expresión de TPH1 y TPH2, SERT y receptores serotoninérgicos con anticuerpos específicos por inmunofluorescencia. La inmunofluorescencia fue analizada por la t de Student, aceptando un nivel de significancia de p < 0.05. RESULTADOS: Se observó un aumento en la expresión de TPH1 y TPH2 y en los receptores 5-HT2A y 5-HT2B en las estructuras dilatadas en comparación con las controles (p < 0.05). El receptor 5-HT4 aumentó su expresión en el septum interventricular dilatado (p < 0.05) y el SERT en la PLVI en comparación con los controles (p < 0.05). CONCLUSIONES: Estos resultados sugieren que los aumentos observados en las expresiones de TPH, SERT y receptores serotoninérgicos en corazones con MCD en comparación con controles podrían desempeñar un papel importante en la fisiopatología de la MCD en los humanos.

Factores predictores de aparición de fibrilación auricular en pacientes con miocardiopatía dilatada / Predicting factors of atrial fibrillation in patients with dilated cardiomyopathy

Resumen Introducción El uso de terapia anticoagulante en pacientes con miocardiopatía dilatada es controvertido. El riesgo hemorrágico hace que habitualmente no se use en pacientes en ritmo sinusal. Objetivo Analizar los factores predictores de fibrilación auricular (FA) en pacientes con miocardiopatía dilatada y fracción de eyección del ventrículo izquierdo (FEVI) < 40. Método: Se estudiaron los pacientes incluidos en el registro multicéntrico UMBRELLA a quienes se había implantado un desfibrilador (DAI) bicameral o tricameral y que presentaban miocardiopatía dilatada isquémica o no isquémica y FEVI < 40%. Se definió FA como cualquier episodio > 30 segundos de duración y una frecuencia auricular > 175 latidos por minuto. Resultados Se incluyeron 684 enfermos. La mediana de edad fue de 70 años (rango intercuartílico [RIQ]: 62-77). El 79.1% eran varones. La FEVI fue < 30% en el 76.3%. El 87.3% presentaban insuficiencia cardiaca (ICC) clínica. Se implantó un DAI resincronizador en el 59.5%. El 51.2% tenían bloqueo de rama izquierda del haz de His y el 7.1% de rama derecha (BRDHH). Se documentó FA en el 49% de los enfermos con una mediana de seguimiento de 29.93 meses (RIQ: 14.78-45.63). Las variables que se relacionaron con la aparición de FA fueron la presencia de ICC (hazard ratio [HR]: 2; intervalo de confianza del 95% [IC 95%]: 1.31-3.04; p = 0.001), el BRDHH (HR: 1.48; IC 95%: 1-2-18; p = 0.045), el ictus previo (HR: 2.11; IC 95%: 1.4-3.19; p < 0.001) y la edad > 75 años (HR: 1.21; IC 95%: 1.05-1.40; p = 0.008). Conclusiones La edad > 75 años, el BRDHH, la ICC y el ictus previo predicen la aparición de FA en la población con miocardiopatía dilatada y FEVI < 40%.

Abstract Introduction Anticoagulant treatment in patients with dilated cardiomyopathy and sinus rhythm is controversial due to haemorrhage risk. Objective To analyze the factors predicting atrial fibrillation (AF) in patients with dilated cardiomyopathy and ejection fraction (LVEF) < 40%. Method All patients included in UMBRELLA multicentre registry without AF, who had a dual or three-chamber implantable cardiac defibrillator (ICD), dilated cardiomyopathy and LVEF < 40% were included. AF was defined as any episode > 30 seconds of duration and atrial frequency > 175 bpm. Results 684 patients were included. Median age was 70 years (IQR 62-77); 79.1% were male. LVEF was < 30% in 76.3% of cases; 87.3% presented clinical heart failure (CHF). A CRT-D was implanted in 59.5%; 51.2% of patients presented Left Bundle Branch Block (LBBB) and 7.1% presented Right Bundle Branch Block (RBBB). AF was documented in 49% of patients, with a median follow-up of 29.93 months (IQR: 14.78-45.63). The presence of CHF (HR: 2; 95% CI: 1.31-3.04; p = 0.001), RBBB (HR: 1.48; 95% CI: 1-2-18; p = 0.045), previous stroke (HR: 2.11; 95% CI: 1.4-3.19; p < 0.001) and age > 75 years (HR: 1.21; 95% CI: 1.05-1.40; p = 0.008) were associated with diagnosis of AF. Conclusions Age > 75 years, RBBB, CHF and previous stroke are predictors of AF development in the population with dilated cardiomyopathy and LVEF < 40%.

Could the unfortunate outcome of pediatric acute myocarditis be predicted? Factors contributing to a poor outcome in myocarditis.

OBJECTIVE: Myocarditis has spontaneous resolution in 50% of patients. Our study aimed to define risk factors for developing dilated cardiomyopathy (DCM) and death in pediatric patients with acute myocarditis (AM). METHODS: The retrospective cohort study included all patients with treated AM. The Mother and Child Health Institute from January 2011 to March 2019. RESULTS: In the study, 62 patients were included, 40 boys and 22 girls (11.15±5.86 years) with AM. Twelve out of sixty-two children had acute fulminant myocarditis. Four patients died in the acute phase of AM, and 11 developed DCM. Follow up was 27.14±36.52 months. Patients with poor outcome (DCM development) were under the age of seven (odds ratio [OR] 10.1; p=0.003), more likely to be girls (OR 4.6; p=0.03), and had fulminant myocarditis (OR 27.0; <0.001). An ejection fraction (EF) <55% and fractional shortening (FS) <30% increased risk of DCM 13- and 5-fold, respectively, but patients with EF between 40 and 55% remain at highest risk of developing DCM. There was a 12-fold increased risk for DCM in patients with left ventricular end-diastolic diameter Z score >2+. The receiver operator curve showed that the lactate dehydrogenase (LDH) cut-off value for developing DCM was 1780 mmol/l (sensitivity 80%, specificity 100%). CONCLUSION: Acute fulminant myocarditis was an independent risk factor for DCM. Children with EF between 40 and 50% at admission were at highest risk of developing DCM. Lactate dehydrogenase value could be a significant prognostic value for the outcome of pediatric myocarditis.

Comportamiento del consumo de oxígeno durante una sesión de rehabilitación cardíaca / Behavior of Oxygen Consumption During a Cardiac Rehabilitation Session

RESUMEN Objetivo: estudiar el comportamiento del consumo de oxígeno en pacientes con miocardiopatía dilatada durante una sesión de rehabilitación cardíaca. Material y métodos: diseño observacional, transversal, analítico relacional. Muestra: 10 pacientes masculinos con miocardiopatía dilatada, con deterioro de moderado a grave de la función ventricular. Se evaluó a los pacientes en laboratorio y en una sesión de rehabilitación mediante un analizador de gases portátil Medgraphics® VO 2000. La sesión de rehabilitación consistió en ejercicios en bicicleta fija de 10 minutos, step, escalera coordinativa, fuerza con mancuerna para bíceps y hombros, cuádriceps en camilla y dorsales en máquina. Resultados: Edad (años) 57,4 ± 14,6. Peso (kg) 91,4 ± 22,2. Talla (cm) 168,1 ± 6,2. Laboratorio: VO2max relativo (ml/kg/min) 21,8 ± 7,3. Tasa de intercambio respiratorio, RER (VCO2/VO2)1,05 ± 0,09. Volumen ventilado (L/min) 65,7 ± 18,5. Frecuencia cardíaca (lat./min) en VO2max 127,8 ± 23,8. Sesión: Duración (min) 37,5 ± 10. VO2pico (ml/kg/min) 14,6 ± 3 (69,9 ± 16,7% del VO2max). Coeficiente de correlación entre VO2max y tiempo con VO2 < 50% del VO2max (min) 0,662 (p = 0,037) y entre VO2pico en rehabilitación y tiempo en RER entre 0,85-1(min) 0,787 (p = 0,007). Los pacientes con mejor aptitud ejercitaron en zona de baja intensidad. Al aumentar el esfuerzo, aumentaron los minutos en intensidad moderada. Conclusión: Se constató en este estudio que los pacientes alcanzaron un VO2pico en las sesiones inferiores a sus máximos obtenidos en laboratorio. Si bien cualquier dosis de entrenamiento en estos pacientes es más beneficiosa que la inactividad física, el diseño y la planificación de las sesiones de RHC, valorando las intensidades de trabajo intrasesión, podrían generar mayor impacto en la mortalidad, las reinternaciones y en la calidad de vida.

ABSTRACT Objective: The aim of this study was to analyze the response of oxygen consumption in patients with dilated cardiomyopathy during a cardiac rehabilitation session. Methods: This was an observational, cross-sectional, relational analytical study. Ten male patients with dilated cardiomyopathy and moderate to severe ventricular dysfunction were included in the study. Patients were evaluated in the laboratory and during a rehabilitation session using a Medgraphics VO 2000 portable gas analyzer. The rehabilitation session consisted in 10 minutes of stationary bike exercises, step, coordinaton stairs, and muscle strength using dumbbells for biceps and shoulder, a quadriceps stretcher and a dorsal muscle machine. Results: Mean age was 57.4 ± 14.6 years, weight 91.4 ± 22.2 kg and height 168.1 ± 6.2 cm. In the laboratory, VO2max was 21.8 ± 7.3 ml/kg/min, respiratory exchange rate (RER) (VCO2/VO2) 1.05 ± 0.09, ventilated volume 65.7 ± 18.5 L/min and heart rate in VO2max 127.8 ± 23.8 beats/min. Rehabilitation session duration was 37.5 ± 10 min with peakVO2 14.6 ± 3 ml kg/min (69.9 ± 16.7 % VO2max). The correlation coefficient between VO2max and time with VO2 <50% VO2max(min) was 0.662 (p = 0.037) and between peakVO2 in rehabilitation and time in RER between 0.85-1 (min) was 0.787 (p = 0.007). Patients with better fitness exercised in the low-intensity zone. As exercise increased, the minutes in moderate intensity also increased. Conclusion: The study showed that patients reached peakVO2 in sessions below the maximum values obtained in the laboratory. Even though any dose of training in these patients was more beneficial than physical inactivity, cardiac rehabilitation session design and planning, taking into account intrasession exercise intensities, could generate greater impact on mortality, rehospitalizations and quality of life.

Utilidad clínica del estudio genético en pacientes con miocardiopatía dilatada / Clinical utility of genetic testing in patients with dilated cardiomyopathy

Introducción y objetivos: La miocardiopatía dilatada (MCD) es la causa más frecuente de trasplante cardiaco. Se considera que es familiar hasta en el 50% de los casos. Nuestro objetivo es describir los resultados genéticos obtenidos en una cohorte de pacientes con MCD, de los cuales una elevada proporción había acabado en trasplante cardiaco.MétodosSe incluyeron pacientes con MCD a los que se realizó next-generation sequencing (NGS, «secuenciación de nueva generación») de al menos 80 genes relacionados con la enfermedad. Se analizaron retrospectivamente los datos clínicos de los pacientes, la historia familiar y los resultados del estudio genético. En los casos en los que fue posible, se realizó una evaluación de sus familiares de primer grado.ResultadosFueron evaluados 87 pacientes con MCD y 308 familiares de 70 familias distintas. La prevalencia clínica de enfermedad familiar fue del 37% (32 pacientes) y el 44% (38 pacientes) habían precisado un trasplante cardiaco. En 43 pacientes (49%) se encontró al menos una variante relevante, en 25 pacientes (29%) se identificaron variantes de significado incierto y en 19 pacientes (22%) el estudio fue negativo. La mayoría de las mutaciones se encontraron en genes sarcoméricos y la rentabilidad del estudio fue mayor en los pacientes con MCD familiar.ConclusionesEl estudio genético NGS en nuestra población de pacientes con MCD tuvo una elevada rentabilidad, alcanzando el 69% en los casos familiares. El espectro mutacional fue heterogéneo y con frecuencia la identificación de la etiología específica de la enfermedad aportó información pronóstica. (AU)

Introduction and objectives: Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation. The prevalence of familial disease can reach 50%. Our objective was to describe the genetic basis of DCM in a cohort with a high proportion of transplanted patients.MethodsWe included patients with DCM and genetic testing performed using next-generation sequencing (NGS) that included at least 80 genes. Clinical data, family history and genetic results were retrospectively analysed. When possible, assessment of first-degree relatives was carried out.ResultsEighty-seven DCM patients and 308 relatives from 70 families were evaluated. Clinical prevalence of familial disease was 37% (32 patients). Forty-four percent of patients (38 patients) had required heart transplantation. A relevant variant was found in 43 patients (49%), 25 patients (29%) carried variants of unknown significance and in 19 patients (22%) the study was negative. Most genetic variants were found in sarcomeric genes and the yield of genetic testing was higher in patients with familial DCM.ConclusionsThe yield of genetic testing in our DCM cohort was high, reaching 69% in familial cases. Mutational spectrum was heterogeneous and the identification of the specific aetiology of the disease often provided prognostic information. (AU)

¿Ayuda la rehabilitación cardíaca a posponer el trasplante cardíaco en la miocardiopatía dilatada? Caso clínico / Does cardiac rehabilitation help postpone heart transplantation in dilated cardiomyopathy? Clinical case

Antecedentes y objetivo La miocardiopatía dilatada es una causa frecuente de trasplante cardíaco y los programas de rehabilitación cardíaca han demostrado ser útiles como parte del tratamiento. El objetivo principal de este trabajo es exponer un caso clínico donde se muestra el impacto del tratamiento de rehabilitación en un paciente con esta enfermedad. Descripción del caso Se presenta el caso de un paciente de 25 años con diagnóstico de miocardiopatía dilatada con New York Heart Association (NYHA) III y fracción de eyección del ventrículo izquierdo (FEVI) del 10%. Presentaba intolerancia al ejercicio, disnea a pequeños-moderados esfuerzos y en espera de trasplante cardíaco. Intervención Ante estos hallazgos, es derivado a programa de rehabilitación cardíaca hospitalaria de alto riesgo para optimizarlo antes del trasplante, donde realizó un programa de ejercicio físico (resistencia aeróbica, fuerza muscular periférica y respiratoria), educación sanitaria y soporte psicológico. Resultados Tras 4 meses de tratamiento el paciente presenta una mejoría clínica y funcional notoria, logrando posponer el trasplante cardíaco. Discusión Los programas de rehabilitación cardíaca pueden suponer un avance terapéutico en la miocardiopatía dilatada. Estos pueden mejorar tanto la tolerancia al ejercicio como parámetros de funcionalidad y en algunos pacientes la fracción de eyección (AU)

Background and objective Dilated cardiomyopathy is a frequent cause of heart transplantation. Cardiac rehabilitation programmes have proven helpful as part of treatment. The main aim of this paper is to present a clinical case showing the impact of rehabilitation treatment on a patient with this pathology. Case description We present the case of a 25-year-old patient diagnosed with dilated cardiomyopathy with New York Heart Association (NYHA) III and 10% left ventricular ejection fraction (LVEF). He had exercise intolerance, dyspnoea on mild-moderate exertion and is awaiting heart transplantation. Intervention Given these findings, the patient was referred to a high-risk hospital cardiac rehabilitation programme for optimization prior to transplantation, where he carried out a programme of physical exercise (aerobic resistance, peripheral muscle, and respiratory strength), health education and psychological support. Results After 4 months of treatment, the patient shows marked clinical and functional improvement, and therefore heart transplantation can be postponed. Discussion Cardiac rehabilitation programmes can be a therapeutic advance in dilated cardiomyopathy. They can improve both exercise tolerance and functionality parameters and, in some patients, the ejection fraction. In this article, an exhaustive review of the rehabilitation treatment of dilated cardiomyopathy is performed (AU)

Predictores de riesgo en una cohorte española con cardiolaminopatías. Registro REDLAMINA / Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry

Introducción y objetivos Según las guías de muerte súbita, se debe considerar un desfibrilador automático implantable (DAI) para los pacientes con miocardiopatía dilatada debida a variantes en el gen de la lamina (LMNA) con al menos 2 factores: varones, fracción de eyección del ventrículo izquierdo (FEVI) <45%, taquicardia ventricular no sostenida (TVNS) y variantes no missense. Nuestro objetivo es describir las características clínicas de una cohorte española de pacientes con cardiolaminopatías (registro REDLAMINA) y evaluar los criterios de riesgo vigentes. Métodos Se evaluó la relación entre factores de riesgo y eventos cardiovasculares en una cohorte de 140 portadores de variantes en LMNA (54 probandos, 86 familiares, edad ≥ 16 años). Se consideró: a) evento arrítmico mayor (EAM) si hubo descarga apropiada del DAI o muerte súbita, y b) muerte por insuficiencia cardiaca, incluidos los trasplantes. Resultados Se identificaron 11 variantes nuevas y 21 previamente publicadas. La FEVI <45% (p=0,001) y la TVNS (p <0,001) se relacionaron con los EAM, pero no el sexo o el tipo de variante (missense frente a no missense). La FEVI <45% (p <0,001) fue el único factor relacionado con la muerte por insuficiencia cardiaca. Conclusiones En el registro REDLAMINA, los únicos 2 predictores asociados con EAM fueron la TVNS y la FEVI <45%. No se debería considerar grupo de bajo riesgo a las portadoras de variantes missense con TVNS o FEVI <45%. Es importante individualizar la estratificación del riesgo de los portadores de variantes missense en LMNA, porque no todas tienen el mismo pronóstico. (AU)

Introduction and objectives According to sudden cardiac death guidelines, an implantable cardioverter-defibrillator (ICD) should be considered in patients with LMNA-related dilated cardiomyopathy (DCM) and ≥ 2 risk factors: male sex, left ventricular ejection fraction (LVEF) <45%, nonsustained ventricular tachycardia (NSVT), and nonmissense genetic variants. In this study we aimed to describe the clinical characteristics of carriers of LMNA genetic variants among individuals from a Spanish cardiac-laminopathies cohort (REDLAMINA registry) and to assess previously reported risk criteria. Methods The relationship between risk factors and cardiovascular events was evaluated in a cohort of 140 carriers (age ≥ 16 years) of pathogenic LMNA variants (54 probands, 86 relatives). We considered: a) major arrhythmic events (MAE) if there was appropriate ICD discharge or sudden cardiac death; b) heart failure death if there was heart transplant or death due to heart failure. Results We identified 11 novel and 21 previously reported LMNA-related DCM variants. LVEF <45% (P=.001) and NSVT (P <.001) were related to MAE, but not sex or type of genetic variant. The only factor independently related to heart failure death was LVEF <45% (P <.001). Conclusions In the REDLAMINA registry cohort, the only predictors independently associated with MAE were NSVT and LVEF <45%. Therefore, female carriers of missense variants with either NSVT or LVEF <45% should not be considered a low-risk group. It is important to individualize risk stratification in carriers of LMNA missense variants, because not all have the same prognosis. (AU)

Deformación miocárdica en miocardiopatía dilatada no isquémica mediante feature tracking. Factibilidad e implicaciones pronósticas / Myocardial strain in nonischemic dilated cardiomyopathy with feature tracking. Feasibility and prognostic implications

Introducción y objetivos El análisis de la deformación miocárdica puede aportar información adicional a la fracción de eyección del ventrículo izquierdo (FEVI) en la miocardiopatía dilatada no isquémica (MDNI). El objetivo es analizar la factibilidad del estudio del strain del ventrículo izquierdo mediante feature tracking (FT) de cardiorresonancia magnética en la MDNI y determinar su relevancia clínica y pronóstica. Métodos Se incluyó retrospectivamente a los pacientes consecutivos con MDNI sometidos a cardiorresonancia magnética. Se obtuvieron el strain global longitudinal, circunferencial y radial del ventrículo izquierdo de secuencias convencionales de cine mediante un software de análisis de FT. Se evaluó su asociación con el evento combinado (insuficiencia cardiaca, implante de desfibrilador en prevención secundaria y muerte). Resultados Se pudo realizar el FT en los 98 pacientes evaluados (edad, 68± 13 años; el 72% varones). La concordancia intraobservador e interobservadores fue buena para el strain global longitudinal y circunferencial, y más limitada para el radial. El strain global circunferencial se asoció de manera independiente (OR=1,16; p=0,045) con la normalización de la FEVI en el seguimiento y fue el único parámetro morfológico con asociación independiente (OR=1,15; p=0,038) con el evento combinado. Un valor <–8,2% fue capaz de predecir la aparición de este evento en el seguimiento (Log-ranktest, 4,6; p=0,032) Conclusiones El análisis del strain del ventrículo izquierdo mediante FT es factible y reproducible en MDNI. El strain global circunferencial fue capaz de predecir la recuperación de la FEVI y la aparición de eventos cardiovasculares mayores en el seguimiento. (AU)

Introduction and objectives Myocardial strain analysis could provide additional information to left ventricular ejection fraction (LVEF) in nonischemic dilated cardiomyopathy (NIDC). Our aim was to analyze the feasibility of left ventricular strain evaluation using cardiac magnetic resonance feature tracking (FT) in NIDC, and to determine its clinical and prognostic impact. Methods We retrospectively included consecutive patients with NIDC who underwent cardiac magnetic resonance. Left ventricular global longitudinal, circumferential and radial strain were obtained from standard cine sequences using FT analysis software. We evaluated their association with a composite endpoint (heart failure, implantable cardioverter-defibrillator in secondary prevention, or death). Results FT analysis could be performed in all of the 98 patients (mean age 68±13 years, 72% men). Intra- and interobserver concordance was good for global longitudinal and circumferential strain but was worse for radial strain. Global circumferential strain was independently associated (OR, 1.16; P=.045) with LVEF normalization during follow-up and was the only morphological parameter independently associated with the composite endpoint (OR, 1.15; P=.038). A cutoff value <−8.2% was able to predict the incidence of this event during follow-up (log-rank 4.6; P=.032). Conclusions Left ventricular strain analysis with FT is feasible and reproducible in NIDC. Global circumferential strain was able to predict LVEF recovery and the appearance of major cardiovascular events during follow-up. (AU)

Ischemic dilated cardiomyopathy pathophysiology through microRNA-16-5p.

INTRODUCTION AND OBJECTIVES: The expression levels of microRNA-16-5p (miR-16) are upregulated in ischemic cardiomyopathy and in animal models of ischemic dilated cardiomyopathy (iDCM), inducing myocardial apoptosis. We investigated the role of miR-16 in the adaptive cellular response associated with endoplasmic reticulum (ER) stress and autophagy in the apoptotic iDCM environment. METHODS: We quantified the miR-16 plasma levels of 168 participants-76 controls, 60 iDCM patients, and 32 familial DCM patients with the pathogenic variant of BAG3-by quantitative real-time polymerase chain reaction and correlated the levels with patient variables. The effects of intracellular miR-16 overexpression were analyzed in a human cardiac cell line. Apoptosis and cell viability were measured, as well as the levels of markers associated with ER stress, cardiac injury, and autophagy. RESULTS: Plasma miR-16 levels were upregulated in iDCM patients (P=.039). A multivariate logistic regression model determined the association of miR-16 with iDCM clinical variables (P <.001). In vitro, miR-16 overexpression increased apoptosis (P=.02) and reduced cell viability (P=.008). Furthermore, it induced proapoptotic components of ER stress, based on upregulation of the PERK/CHOP pathway. However, we observed augmentation of autophagic flux (P <.001) without lysosomal blockade by miR-16 as a possible cytoprotective mechanism. CONCLUSIONS: MiR-16 is specifically associated with iDCM. In an ischemic setting, miR-16 activates ER stress and promotes inflammation followed by autophagy in human cardiac cells. Thus, autophagy may be an attempt to maintain cellular homeostasis in response to misfolded/aggregated proteins related to ER stress, prior to apoptosis.

Risk predictors in a Spanish cohort with cardiac laminopathies. The REDLAMINA registry.

INTRODUCTION AND OBJECTIVES: According to sudden cardiac death guidelines, an implantable cardioverter-defibrillator (ICD) should be considered in patients with LMNA-related dilated cardiomyopathy (DCM) and ≥ 2 risk factors: male sex, left ventricular ejection fraction (LVEF) <45%, nonsustained ventricular tachycardia (NSVT), and nonmissense genetic variants. In this study we aimed to describe the clinical characteristics of carriers of LMNA genetic variants among individuals from a Spanish cardiac-laminopathies cohort (REDLAMINA registry) and to assess previously reported risk criteria. METHODS: The relationship between risk factors and cardiovascular events was evaluated in a cohort of 140 carriers (age ≥ 16 years) of pathogenic LMNA variants (54 probands, 86 relatives). We considered: a) major arrhythmic events (MAE) if there was appropriate ICD discharge or sudden cardiac death; b) heart failure death if there was heart transplant or death due to heart failure. RESULTS: We identified 11 novel and 21 previously reported LMNA-related DCM variants. LVEF <45% (P=.001) and NSVT (P <.001) were related to MAE, but not sex or type of genetic variant. The only factor independently related to heart failure death was LVEF <45% (P <.001). CONCLUSIONS: In the REDLAMINA registry cohort, the only predictors independently associated with MAE were NSVT and LVEF <45%. Therefore, female carriers of missense variants with either NSVT or LVEF <45% should not be considered a low-risk group. It is important to individualize risk stratification in carriers of LMNA missense variants, because not all have the same prognosis.

Myocardial strain in nonischemic dilated cardiomyopathy with feature tracking. Feasibility and prognostic implications.

INTRODUCTION AND OBJECTIVES: Myocardial strain analysis could provide additional information to left ventricular ejection fraction (LVEF) in nonischemic dilated cardiomyopathy (NIDC). Our aim was to analyze the feasibility of left ventricular strain evaluation using cardiac magnetic resonance feature tracking (FT) in NIDC, and to determine its clinical and prognostic impact. METHODS: We retrospectively included consecutive patients with NIDC who underwent cardiac magnetic resonance. Left ventricular global longitudinal, circumferential and radial strain were obtained from standard cine sequences using FT analysis software. We evaluated their association with a composite endpoint (heart failure, implantable cardioverter-defibrillator in secondary prevention, or death). RESULTS: FT analysis could be performed in all of the 98 patients (mean age 68±13 years, 72% men). Intra- and interobserver concordance was good for global longitudinal and circumferential strain but was worse for radial strain. Global circumferential strain was independently associated (OR, 1.16; P=.045) with LVEF normalization during follow-up and was the only morphological parameter independently associated with the composite endpoint (OR, 1.15; P=.038). A cutoff value <-8.2% was able to predict the incidence of this event during follow-up (log-rank 4.6; P=.032). CONCLUSIONS: Left ventricular strain analysis with FT is feasible and reproducible in NIDC. Global circumferential strain was able to predict LVEF recovery and the appearance of major cardiovascular events during follow-up.

Clinical utility of genetic testing in patients with dilated cardiomyopathy. / Utilidad clínica del estudio genético en pacientes con miocardiopatía dilatada.

INTRODUCTION AND OBJECTIVES: Dilated cardiomyopathy (DCM) is the most frequent cause of heart transplantation. The prevalence of familial disease can reach 50%. Our objective was to describe the genetic basis of DCM in a cohort with a high proportion of transplanted patients. METHODS: We included patients with DCM and genetic testing performed using next-generation sequencing (NGS) that included at least 80 genes. Clinical data, family history and genetic results were retrospectively analysed. When possible, assessment of first-degree relatives was carried out. RESULTS: Eighty-seven DCM patients and 308 relatives from 70 families were evaluated. Clinical prevalence of familial disease was 37% (32 patients). Forty-four percent of patients (38 patients) had required heart transplantation. A relevant variant was found in 43 patients (49%), 25 patients (29%) carried variants of unknown significance and in 19 patients (22%) the study was negative. Most genetic variants were found in sarcomeric genes and the yield of genetic testing was higher in patients with familial DCM. CONCLUSIONS: The yield of genetic testing in our DCM cohort was high, reaching 69% in familial cases. Mutational spectrum was heterogeneous and the identification of the specific aetiology of the disease often provided prognostic information.

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.

The value of hypotensive prediction index and dP/dtmax to predict and treat hypotension in a patient with a dilated cardiomyopathy. / Valor del índice de predicción de la hipotensión y el dP/dtmax para predecir y tratar la hipotensión en un paciente con miocardiopatía dilatada.

The Hypotension Prediction Index (HPi) is a new parameter, recently developed to predict the risk of a patient developing a hypotensive event, defined as a fall in mean arterial pressure below 65 mmHg. The calculated HPi value is displayed on a monitor as a number ranging from 1 to 100; where the first warning for the appearance of such event occurs when HPi values exceed 85. A secondary screen shows the stroke volume variation value; the dP/dt max; and the dynamic arterial elastance. We described a patient with a mild to moderately dilated cardiomyopathy that presented several episodes of hypotension after induction of anaesthesia and how by using HPi technology, these were successfully solved. We recommend the use of a HPi value >85 as a warning of intervention, and to use the secondary screen to determine the cause and the treatment. We consider that HPi technology may be a valid alternative for the anaesthetic management of patients with a dilated cardiomyopathy.

Miocardiopatía dilatada idiopática en paciente embarazada asintomática / Idiopathic dilated cardiomyopathy in an asymptomatic pregnant patient

RESUMEN La miocardiopatía dilatada en el embarazo es, generalmente, de origen desconocido, pero en un 20-35% es hereditaria. Se presenta el caso de una paciente de 22 años de edad, con 34,6 semanas de gestación, primípara, con antecedente de asma bronquial leve, que se encontraba asintomática desde el punto de vista cardiovascular, hasta que se encontró una frecuencia cardíaca mayor de 130 latidos por minuto y edema en miembros inferiores que fue la causa de la consulta de Cardiología. El ecocardiograma transtorácico reveló una miocardiopatía dilatada con función ventricular izquierda gravemente deprimida, disfunción diastólica, insuficiencia tricuspidea grave y mitral moderada, e hipertensión pulmonar leve. Se consideró muy alto riesgo obstétrico (grupo IV de la clasificación de la Organización Mundial de la Salud) y, previa coordinación con el servicio nacional de cardiopatía y embarazo, se envió a la paciente al centro de referencia donde se realizó cesárea sin complicaciones.

ABSTRACT Dilated cardiomyopathy in pregnancy is generally of unknown origin, but in 20-35% it is hereditary. Here is presented the case of a 22-year-old patient, 34.6 weeks of pregnancy, primipara, with a history of slight bronchial asthma, who was asymptomatic from the cardiovascular point of view, until a heart rate greater than 130 beats per minute and edema in lower limbs were found, which were the causes that bring her to the Department of Cardiology. The transthoracic echocardiogram revealed dilated cardiomyopathy with severely depressed left ventricular function, diastolic dysfunction, severe tricuspid and moderate mitral regurgitations, as well as slight pulmonary hypertension. It was considered a very high obstetric risk (group IV of the World Health Organization Classification) and, after coordinating with the national department of heart disease and pregnancy, the patient was sent to the reference center, where a cesarean section was performed without complications.