Depressed myocardial cross-bridge cycling kinetics in a female guinea pig model of diastolic heart failure.

Cardiac hypertrophy is associated with diastolic heart failure (DHF), a syndrome in which systolic function is preserved but cardiac filling dynamics are depressed. The molecular mechanisms underlying DHF and the potential role of altered cross-bridge cycling are poorly understood. Accordingly, chronic pressure overload was induced by surgically banding the thoracic ascending aorta (AOB) in ∼400 g female Dunkin Hartley guinea pigs (AOB); Sham-operated age-matched animals served as controls. Guinea pigs were chosen to avoid the confounding impacts of altered myosin heavy chain (MHC) isoform expression seen in other small rodent models. In vivo cardiac function was assessed by echocardiography; cardiac hypertrophy was confirmed by morphometric analysis. AOB resulted in left ventricle (LV) hypertrophy and compromised diastolic function with normal systolic function. Biochemical analysis revealed exclusive expression of ß-MHC isoform in both sham control and AOB LVs. Myofilament function was assessed in skinned multicellular preparations, skinned single myocyte fragments, and single myofibrils prepared from frozen (liquid N2) LVs. The rates of force-dependent ATP consumption (tension-cost) and force redevelopment (Ktr), as well as myofibril relaxation time (Timelin) were significantly blunted in AOB, indicating reduced cross-bridge cycling kinetics. Maximum Ca2+ activated force development was significantly reduced in AOB myocytes, while no change in myofilament Ca2+ sensitivity was observed. Our results indicate blunted cross-bridge cycle in a ß-MHC small animal DHF model. Reduced cross-bridge cycling kinetics may contribute, at least in part, to the development of DHF in larger mammals, including humans.

Utility of Three-Dimensional Printed Model in Biventricular Repair of Complex Congenital Cardiac Defects: Case Report and Review of Literature.

Heterotaxy is a rare syndrome associated with cardiac complexity, anatomic variability and high morbidity and mortality. It is often challenging to visualize and provide an accurate diagnosis of the cardiac anatomy prior to surgery with the use of conventional imaging techniques. We report a unique case demonstrating how the use of three-dimensional (3D) cardiac printed model allowed us to better understand the anatomical complexity and plan a tailored surgical approach for successful biventricular repair in a patient with heterotaxy syndrome.

Skeletal myopathy in a rat model of postmenopausal heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of all patients with heart failure and frequently affects postmenopausal women. The HFpEF condition is phenotype-specific, with skeletal myopathy that is crucial for disease development and progression. However, most of the current preclinical models of HFpEF have not addressed the postmenopausal phenotype. We sought to advance a rodent model of postmenopausal HFpEF and examine skeletal muscle abnormalities therein. Female, ovariectomized, spontaneously hypertensive rats (SHRs) were fed a high-fat, high-sucrose diet to induce HFpEF. Controls were female sham-operated Wistar-Kyoto rats on a lean diet. In a complementary, longer-term cohort, controls were female sham-operated SHRs on a lean diet to evaluate the effect of strain difference in the model. Our model developed key features of HFpEF that included increased body weight, glucose intolerance, hypertension, cardiac hypertrophy, diastolic dysfunction, exercise intolerance, and elevated plasma cytokines. In limb skeletal muscle, HFpEF decreased specific force by 15%-30% (P < 0.05) and maximal mitochondrial respiration by 40%-55% (P < 0.05), increased oxidized glutathione by approximately twofold (P < 0.05), and tended to increase mitochondrial H2O2 emission (P = 0.10). Muscle fiber cross-sectional area, markers of mitochondrial content, and indices of capillarity were not different between control and HFpEF in our short-term cohort. Overall, our preclinical model of postmenopausal HFpEF recapitulates several key features of the disease. This new model reveals contractile and mitochondrial dysfunction and redox imbalance that are potential contributors to abnormal metabolism, exercise intolerance, and diminished quality of life in patients with postmenopausal HFpEF.NEW & NOTEWORTHY Heart failure with preserved ejection fraction (HFpEF) is a condition with phenotype-specific features highly prevalent in postmenopausal women and skeletal myopathy contributing to disease development and progression. We advanced a rat model of postmenopausal HFpEF with key cardiovascular and systemic features of the disease. Our study shows that the skeletal myopathy of postmenopausal HFpEF includes loss of limb muscle-specific force independent of atrophy, mitochondrial dysfunction, and oxidized shift in redox balance.

Standardized, Patient-specific, Postoperative Opioid Prescribing After Inpatient Orthopaedic Surgery.

BACKGROUND: Opioid-related mortality has increased over the past 2 decades, leading to the recognition of a nationwide opioid epidemic and prompting physicians to reexamine their opioid prescribing practices. At our institutions, we had no protocol for prescribing opioids upon discharge after inpatient orthopaedic surgery, resulting in inconsistent and potentially excessive prescribing. Here, we report the results of the implementation of a patient-specific protocol using an opioid taper calculator to standardize opioid prescribing at discharge after inpatient orthopaedic surgery. METHODS: The opioid taper calculator is a tool that creates a patient-specific opioid taper based on each patient's 24-hour predischarge opioid utilization. We implemented this taper for patients discharged after inpatient orthopaedic surgery at our two institutions (Boston Medical Center and Lahey Hospital and Medical Center-Burlington Campus). We compared discharge opioid quantities between orthopaedic patients postimplementation and quantities prescribed preimplementation. We also compared discharge opioid quantities between orthopaedic and nonorthopaedic surgical services over the same time period. RESULTS: Nine-months postimplementation, a patient-specific taper was used in 74% of eligible discharges, resulting in a 24% reduction in opioids prescribed at discharge, along with a 35% reduction in variance. Over the same time frame, a smaller reduction (9%) was seen in the opioids prescribed at discharge by nonorthopaedic services. The most notable reductions were seen after total joint arthroplasty and spinal fusions. Despite this reduction, most patients (65%) reported receiving sufficient opioids, and no substantial change was observed in 30-day postdischarge opioid prescription refills after versus before protocol implementation (1.58 versus 1.71 fills per discharge). DISCUSSION: Using the opioid taper calculator, a patient-specific taper can be successfully used to standardize opioid prescribing at discharge after inpatient orthopaedic surgery without a substantial risk of underprescription. LEVEL OF EVIDENCE: Level II.

Factores de riesgo asociados a estancia hospitalaria prolongada en pacientes con falla cardiaca aguda / Risk factors associated with prolonged hospital stay in patients with acute heart failure

Resumen Introducción:: La falla cardiaca aguda es un motivo frecuente de consulta a urgencias, genera estancias hospitalarias prolongadas y altos costos para el sistema de salud. Objetivo: Determinar los factores asociados a estancia hospitalaria prolongada en pacientes hospitalizados por falla cardiaca aguda en un hospital universitario. Métodos: Estudio de cohorte retrospectivo, se incluyeron pacientes adultos con falla cardiaca aguda. Se obtuvieron variables demográficas, comorbilidades y resultados de laboratorios de rutina. Se definió hospitalización prolongada, como una estancia mayor a 5 y 10 días respectivamente. Resultados: Un total de 776 pacientes fueron incluidos en el análisis, 56% eran hombres, el promedio de edad fue de 71.5 años, fracción de eyección de 39.8%. Los factores asociados con estancia hospitalaria prolongada fueron: edad, elevación de troponina, hiperglucemia y albúmina < 3 g/dl. Para el corte de 10 días adicionalmente se identificaron: presión arterial sistólica, frecuencia cardiaca y elevación de péptidos natriuréticos. Conclusiones: La evaluación integral de variables clínicas y resultados de laboratorio es útil para identificar pacientes con mayor riesgo de estancias hospitalarias prolongadas.

Abstract Introduction: Acute heart failure is a frequent reason for consulting to emergency department, it generates long hospital stays and high costs for the health system. Objective: To determine the associated factors with prolonged hospital stay in patients hospitalized for acute heart failure in a teaching hospital. Methods: Retrospective cohort study, adult patients with acute heart failure were included. Demographic variables, comorbidities, and routine laboratory results were obtained. Prolonged hospitalization was defined as a stay greater than 5 and 10 days, respectively. Results: A total of 776 patients were included in the analysis, 56% were men, the mean age was 71.5 years, and ejection fraction was 39.8%. Factors associated with prolonged hospital stay were: age, elevated troponin, hyperglycemia, and albumin < 3 g/dl. For the 10-day cut-off, additionally, systolic blood pressure, heart rate and elevation of natriuretic peptides were identified. Conclusions: Comprehensive evaluation of clinical variables and laboratory results is useful to identify patients at increased risk for prolonged hospital stays.

Total cholesterol in dyslipidemias. Is it a useful measure? / Colesterol total en dislipidemias. ¿Útil medirlo?

Abstract Introduction: the relationship between lipid fractions and cardiovascular risk is clear. However, the operational characteristics of total cholesterol (TC) for the diagnosis of dyslipidemias due to elevated LDL cholesterol (LDLC), hypertriglyceridemia and low HDL cholesterol (HDLC) are not clear. Objective: to establish the sensitivity (Sen) specificity (Spe) and predictive values (PPV and NPV) of TC (>200 mg/dL) for diagnosing various types of dyslipidemias. Materials and methods: a study of diagnostic tests using all the lipid profiles processed at the Hospital Universitario San Ignacio in Bogotá (Colombia) from January 2006 to January 2017. Sensitivity, Spe, PPV and NPV were calculated for each dyslipidemia and for each LDLC goal. Results: in 25,754 profiles, the average age was 53.6±18 years. The prevalence of elevated LDLC (based on the goals of 160, 130, 100, 70 or 55 mg/dL) was: 19.9%, 44.5%, 72.7%, 92.1% and 96.8%, respectively; for hypertriglyceridemia (>150 mg/dL) it was 44.7%, and for low HDLC (< 40 mg/dL) it was 33.9%. The sensitivity of TC (>200 mg/dL) for elevated LDLC according to the same goals was: 100%, 95%, 70%, 56% and 53%, with a specificity of: 59%, 81%, 94%, 95% and 92%; PPV=37%, 80%, 97%, 99% and 99%; and NPV=100%, 95%, 54%, 15% and 5.8%. For hypertrygliceridemia: Sen=61%, Spe=61%, PPV=55% and NPV=66%. For low HDLC: Sen=36%, Spe=42%, PPV=26% and NPV=54%. Conclusions: given the operational characteristics of TC>200 mg/dL, it should not be used as an isolated tool for diagnosing dyslipidemia due to LDLC, HDLC or hypertriglyceridemia. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1320).

Resumen Introducción: es clara la relation entre las fracciones lipídicas y riesgo cardiovascular, sin embargo, no son claras las características operativas del colesterol total (CT) para el diagnóstico de dislipidemias por colesterol LDL (C-LDL) elevado, hipertrigliceridemia y colesterol HDL (C-HDL) bajo. Objetivo: establecer sensibilidad (S), especificidad (E), y valores predictivos (VPP y VPN) del CT (>200 mg/dL) para diagnóstico de diferentes tipos de dislipidemias. Material y métodos: estudio de pruebas diagnosticas a partir de la totalidad de perfiles lipídicos procesados en el Hospital Universitario San Ignacio de Bogotá (Colombia), desde enero de 2006 hasta enero de 2017. Se calcularon S, E, VPP y VPN para cada dislipidemia y para cada meta de C-LDL. Resultados: en 25 754 perfiles, la edad promedio fue 53.6±18 años. Las prevalencias de C-LDL elevado (según metas de 160, 130, 100, 70 o 55 mg/dL) fueron: 19.9%, 44.5%, 72.7%, 92.1% y 96.8% respectivamente; hipertrigliceridemia (>150 mg/dL) 44.7% y C-HDL bajo (< 40 mg/dL) 33.9%. Las sensibilidades del CT (>200 mg/dL) para C-LDL elevado según las mismas metas fueron: 100%, 95%, 70%, 56% y 53% y especificidades: 59%, 81%, 94%, 95% y 92%. VPP=37%, 80%, 97%, 99% y 99%, y VPN=100%, 95%, 54%, 15% y 5.8%. Para hipertrigliceridemia: S=61%, E=61%, VPP=55% y VPN=66%. Para C-HDL bajo: S=36%, E=42%, VPP=26% y VPN=54%. Conclusiones: dadas las características operativas del CT>200 mg/dL, éste no debe ser utilizado como herramienta aislada para el diagnóstico de dislipidemia por C-LDL, por C-HDL, ni para hipertrigliceridemia. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1320).

Miocarditis eosinofílica como causa de disfunción ventricular izquierda reversible / Eosinophilic myocarditis as a cause of reversible left ventricular dysfunction

Resumen La miocarditis eosinofílica es una entidad poco difundida ya que su diagnóstico histopatológico se realiza en casos de mayor severidad, donde la biopsia endomiocárdica es mandatoria. No obstante, dado que esta entidad suele superponerse a muchas patologías: las infecciosas, las inmunológicas, o asociadas a la hipersensibilidad y esto se asocia con la reversibilidad, es importante tenerla presente como entidad nosológica en cuadros agudos de la disfunción ventricular izquierda. Puede o no estar asociada a la eosinofilia periférica, su ausencia no descarta la enfermedad. Se presenta un paciente joven (35 años de edad), con un cuadro clínico de la falla cardiaca aguda que progresa rápidamente a choque cardiogénico con poca respuesta al manejo inicial instaurado (inodilatadores, vasopresores), requiriendo el uso de soporte circulatorio extracorpóreo. Como antecedente: la reciente finalización del tratamiento para leishmaniasis mucocutánea, con antimoniato de meglumina (glucantime). Informe del servicio de patología: miocarditis eosinofílica. Se logra el destete del soporte circulatorio, presenta mejoría de la función sistólica del ventrículo izquierdo con recuperación total del cuadro clínico. Este caso es relevante en cuanto a diagnóstico de disfunción ventricular aguda, con una asociación previamente no descrita con antimoniato de meglumina (glucantime), nos recuerda la importancia de realizar: la biopsia endomiocárdica para definir la etiología, la toma de decisiones de terapias avanzadas, conociendo que en ciertas circunstancias puede presentarse reversibilidad de la disfunción miocárdica y mejoría del cuadro clínico.

Abstract Eosinophilic myocarditis is a little-known entity as its histopathological diagnosis is conducted in the most severe cases, where an endomyocardial biopsy is mandatory. However, because this condition is usually overlaps with many pathologies -infectious, immunological, or associated to hypersensitivity, and this is related to reversibility- it is important to keep it in mind as a nosological entity in acute presentations of left ventricular dysfunction. It may or may not be associated to peripheral eosinophilia, though its absence does not rule out the condition. A case of a young male patient (35 year-old) with clinical features of acute cardiac failure which progresses rapidly into cardiogenic shock with low response to initial management (inodilators, vasopressors) requiring the use of extracorporeal circulation support is presented. Previous history: recent completion of treatment for ucocutaneous leishmaniases with meglumine antimoniate (glucantime). Pathology service report: eosinophilic yocarditis. Weaning from circulatory support is achieved, presenting an improvement of systolic function of the left ventricle with complete recovery of the symptomatology. This case is relevant due to the diagnosis of acute ventricular dysfunction with an association with meglumine antimoniate (glucantime) that was previously not described. It reminds of the importance of carrying out an endomyocardial biopsy in order to define the aetiology and the decision-making on advances therapies, knowing that in some circumstances there can be a reversibility of the myocardial function and an improvement of the symptomatology.

Síndrome de encefalopatía posterior reversible secundaria a tacrolimus / Tacrolimus-associated posterior reversible encephalopathy syndrome

Los inhibidores de la calcineurina, la ciclosporina y el tacrolimus han jugado un papel preponderante en la prevención de los episodios de rechazo y de la enfermedad de injerto contra el huésped en pacientes tratados mediante el trasplante de órgano sólido y de la médula ósea. No obstante, el tacrolimus presenta efectos adversos relacionados con la neurotoxicidad, siendo el síndrome de encefalopatía posterior reversible la consecuencia más severa de dicha neurotoxicidad. El reporte de nuestro caso es de una mujer de 30 años de edad, con 2 días de evolución de cefalea intensa en la frente, náuseas, emesis, hiporexia y epigastralgia, afebril. Antecedente de un trasplante cardiaco 45 días antes, en tratamiento inmunosupresor con tacrolimus y micofenolato mofetilo. Se documentan niveles de tacrolimus adecuados (12,1 ng/ml), los estudios imagenológicos normales y los resultados de laboratorio negativos para infección, lo que permite descartar las causas vasculares e infecciosas y la neurotoxicidad por el tacrolimus. Sin embargo, ante el desarrollo de alteraciones neuropsiquiátricas, y a pesar de niveles de tacrolimus < 5,5 ng/ml, se realiza nueva resonancia nuclear magnética cerebral con hallazgos que indican síndrome de leucoencefalopatía posterior reversible. Se suspende el tacrolimus y se inicia tratamiento con everolimus, lográndose remisión total. Este sería el primer caso reportado en el cual las alteraciones imagenológicas asociadas al síndrome de encefalopatía posterior reversible se desarrollaron en una paciente intervenida de trasplante cardiaco con niveles de tacrolimus < 10 ng/ml. El reporte de este caso permitirá a los grupos médicos tratantes considerar este diagnóstico a pesar de niveles de tacrolimus en rango terapéutico, de manera que se realice un reconocimiento y tratamiento oportuno, evitando así el desarrollo de complicaciones o secuelas neurológicas.

Calcineurin inhibitors, cyclosporine and tacrolimus, have played a major role in preventing graft rejection and graft-versus-host disease in patients undergoing bone marrow and solid organ transplantation. However, tacrolimus has adverse effects related with neurotoxicity, being the posterior reversible encephalopathy syndrome the most severe consequence of this neurotoxicity. We report the case of a 30 year-old woman with 2-day history of severe frontal headache, náusea, emesis, hiporexia and epigastric pain, without fever. History of heart transplant 45 days ago, immunosuppressive therapy with tacrolimus and mycophenolatemofetil. Appropriate levels of tacrolimus (12.1 ng/ml), normal imaging and lab results were documented, excluding vascular and infectious causes as well as tacrolimus neurotoxicity. Nevertheless, due to the development of neuropsychiatric disorders and despite tacrolimus levels being < 5.5 ng/ml, a new brain MRI was performed showing a reversible posterior leukoencephalopathy syndrome. Tacrolimus was switched to everolimus achieving complete remission. This is the first reported case in which the imaging alterations associated with posterior reversible encephalopathy syndrome were developed in a patient undergoing heart transplantation with tacrolimus levels < 10 ng/ml. The report of this case will allow the treating physician groups to consider this diagnosis regardless oftacrolimus levels within therapeutic range, allowing therefore an early recognition and treatment, thus avoiding the development of complications and/or neurological sequels.

Tuberculoma epidural espinal simulando Síndrome de Guillain-Barré: presentación de un caso / Spinal epidural tuberculoma simulating Guillain-Barré syndrome: case report

El sistema nervioso central es uno de los focos extrapulmonares afectados con mayor frecuencia por tuberculosis, no obstante, el tuberculoma epidural espinal es considerado una rareza. Se presenta el caso de un paciente de cuatro años de edad, quien consulta por cuadro de cuadriparesia progresiva. Al examen de líquido cefalorraquídeo se evidenció disociación proteínico celular diagnosticándose síndrome de Guillain Barré, sin embargo, tras la aparición de signos meníngeos, se realizó una resonancia nuclear magnética de columna en la que se evidenció lesión compresiva a nivel cervicodorsal que fue posteriormente explorada quirúrgicamente por neurocirugía, encontrándose una lesión epidural cuyo estudio microbiológico, cultivo y estudio de reacción en cadena de la polimerasa se reportaron positivos para Mycobacterium tuberculosis, por lo que se inició tratamiento antituberculoso observándose mejoría clínica y progresiva con recuperación de la marcha tras el procedimiento quirúrgico. MÉD.UIS. 2016;29(2):155-9.

The central nervous system is one of the most affected focus in extrapulmonary tuberculosis, however, spinal epidural tuberculoma is considered very unusual. We present a clinical report of a four years old patient who presented with clinical symptoms of a progressive quadriparesis. The cerebroespinal fluid examination showed protein-cell dissociation, and the diagnosis of Guillain Barré syndrome was made. However, because it called the attention the appearance of meningeal signs, a magnetic resonance imaging was performed, and evidenced a compressive lesion in the cervicodorsal level. It was explored by neurosurgery, finding an epidural lesion studied by cultures and polymerase chain reaction. Both reported positive results for Mycobacterium tuberculosis. The anti-tuberculosis treatment was started and a progressive clinical improvement was observed with recuperation of the gait after the surgical procedure.MÉD.UIS. 2016;29(2):155-9.

Aborto Recurrente de Etiología Autoinmune / Autoimmune Recurrent Abortion

El curso normal del embarazo implica una serie de cambios inmunológicos que permiten el desarrollo armónico fetal. En mujeres con pérdida recurrente de la gestación, diversas etiologías se han relacionado como desencadenantes de dichas pérdidas; jugando el factor autoinmune un papel cada vez más importante. En el presente artículo, a partir de una búsqueda sistemática de información, se exponen en detalle los aspectos inmunológicos del embarazo normal, así como las alteraciones que a este nivel se presentan en mujeres con aborto recurrente. Además, se realiza una orientación diagnóstica y se exponen las diversas opciones terapéuticas utilizadas, haciendo énfasis en la necesidad de establecer protocolos estandarizados para el manejo de esta entidad.

Normal development of the pregnancy involves a number of immunological changes that allow harmonic fetal development. In women with recurrent pregnancy loss several etiologies have been implicated as triggers of such losses; autoimmune factor is nowadays playing an increasingly more important roll. In this article, based on a systematic search of information, are exposed in details the immunological aspects of normal pregnancy, as well as the immune alterations that occur in women with recurrent abortion. In addition, a diagnostic guidance is made and the various therapeutic options used are pointed out, emphasizing the need to establish standardized protocols for the management of this entity.

Aborto recurrente de etiología aloinmune / Alloimmune recurrent spontaneous abortion

Los mecanismos que subyacen la reproducción humana son muy complejos, por lo que cualquier pérdida gestacional implica el tener que considerar diversas etiologías, más aun si se trata de pérdidas gestacionales recurrentes dentro de las que la inmunidad juega un papel especialmente importante. Desde hace varias décadas, el factor aloinmune ha sido reconocido como un desencadenante frecuente de la interrupción del embarazo, haciéndose de esta forma relevante su estudio en mujeres con aborto recurrente. En el presente artículo, a partir de una búsqueda sistemática de información, se revisan con detalle los aspectos relacionados con la fisiopatología, el diagnóstico y el tratamiento del aborto recurrente de etiología aloinmune, buscando con esto sensibilizar al profesional de la salud sobre su consideración ante una mujer con pérdida recurrente de la gestación.

The mechanisms underlying the human reproduction are very complex, so any pregnancy loss implies the need of considering various etiologies, even more if those pregnancy losses are recurrent within which the immunity plays an important role. Since decades, the alloimmune factor has been recognized as a frequent trigger of the pregnancy interruption, thus becoming relevant its study in women with recurrent miscarriage. In the present article, through a systematic search of information, details concerning to the physiopathology, diagnosis and treatment of the recurrent miscarriage of alloimmune etiology are reviewed, looking to sensitize the health professional about its consideration when evaluating a woman with recurrent pregnancy loss.