Cardiomiopatía amiloídea por transtiretina: diagnóstico y manejo en la actualidad / Transthyretin amyloid cardiomyopathy: a review

RESUMEN: La cardiomiopatía amiloide por transtiretina (CATTR) es una enfermedad caracterizada por depósito extracelular de fibrillas amiloides en el miocardio, a partir de transtiretina mal plegada, generando una miocardiopatía restrictiva. Esta proteína mal plegada puede tener origen hereditario o adquirido, siendo más frecuente en adultos mayores. La CA-TTR ha surgido como una causa subdiagnosticada de insuficiencia cardíaca con fracción de eyección preservada (IC FEp). El pilar fundamental para su diagnóstico es la alta sospecha clínica, basada en diversas banderas de alerta ya que la sintomatología que provoca suele ser inespecífica. Como veremos en esta revisión, el diagnóstico puede sustentarse con la cintigrafía ósea, reservando para situaciones particulares la toma de biopsia. Con el advenimiento de nuevas terapias que impactan en la sobrevida de esta enfermedad, el tiempo para realizar el diagnóstico certero y la diferenciación de otras causas de amiloidosis cardíaca como la de cadenas livianas, se ha tornado crucial.

ABSTRACT: Transthyretin amyloid cardiomyopathy (AT-TR-CM) is a disease characterized by extracellular deposition of amyloid fibrils in the myocardium, from misfolded transthyretin, generating a restrictive cardiomyopathy. This misfolded protein may be inherited or acquired, and is more prevalent in elderly patients. ATTR-CM has emerged as an underdiagnosed cause of heart failure with preserved ejection fraction (HF-PEF). The fundamental pillarfor its diagnosis is high clinical suspicion since the symptoms are usually nonspecific. The diagnosis can be made from bone scintigraphy, reserving myocardial biopsy for particular situations. With the advent of new therapies that affect the survival of these patients, a timely diagnosis has become crucial.

Estudio y manejo de nódulos tiroideos por médicos no especialistas. Consenso SOCHED / Study and management of thyroid nodes by non specialist physicians: SOCHED consensus

The thyroid nodule is a frequent cause of primary care consultation. The prevalence of a palpable thyroid nodule is approximately 4-7%, increasing up to 67% by the incidental detection of nodules on ultrasound. The vast majority are benign and asymptomatic, staying stable over time. The clinical importance of studying a thyroid nodule is to exclude thyroid cancer, which occurs in 5 to 10% of the nodules. The Board of SOCHED (Chilean Society of Endocrinology and Diabetes) asked the Thyroid Study Group to develop a consensus regarding the diagnostic management of the thyroid nodule in Chile, aimed at non-specialist physicians and adapted to the national reality. To this end, a multidisciplinary group of 31 experts was established among university academics, active researchers with publications on the subject and prominent members of scientific societies of endocrinology, head and neck surgery, pathology and radiology. A total of 14 questions were developed with key aspects for the diagnosis and subsequent referral of patients with thyroid nodules, which were addressed by the participants. In those areas where the evidence was insufficient or the national reality had to be considered, the consensus opinion of the experts was used through the Delphi methodology. The consensus was approved by the SOCHED board for publication.

Descripción de los hallazgos en el perfil lipídico y proteico de pacientes dependientes a cocaína, en abstinencia reciente / Serum lipid levels in a group of cocaine dependent subjects in recent abstinence

Background: Chronic cocaine users develop multiple potentially lethal ischemic vascular complications associated with accelerated atherosclerosis. Aim: To assess biochemical and lipid profiles among cocaine dependent subjects in recent abstinence. Material and Methods: A blood sample to measure blood count, biochemical and lipid profiles was obtained from 78 patients aged 19 to 53 years (78% males) who complied with DSM-IV criteria for cocaine dependency. Laboratory results were compared with a group of normal subjects. Results: All cases had positive urinary cocaine, with a mean consumption lapse of 7.6 years. The frequency of smoking was higher in cases. Dependent males had higher body mass index than controls. Compared to controls, dependent females had significantly higher triglyceride (TG) levels and lower HDL cholesterol. Therefore the relation total/HDL cholesterol was higher (p = 0.0365). Dependent males had higher TG levels than their normal counterparts. Dependent subjects consuming cocaine base-paste had higher TG levels. Total proteins, albumin, urea and blood urea nitrogen were lower in dependent subjects. Among males, serum creatinine was lower and blood urea was positively correlated with the daily amount of cocaine use (p = 0.03). After a month of strict abstinence, lipid profile was repeated in 27 patients and remained unchanged. Conclusions: Chronic cocaine use was associated with higher TG in both genders and lower HDL cholesterol in women when compared with a group of healthy counterparts.

Seguimiento a cinco años en pacientes diabéticos sin síntomas cardíacos estudiados con perfusión miocárdica / Myocardial perfusion studies in asymptomatic patients with diabetes mellitus are controversial

Antecedentes: El rendimiento del estudio de perfusión miocárdica en pacientes con Diabetes Mellitus (DM) y sin síntomas coronarios es controvertido. Objetivo: Efectuar un seguimiento a 5 años para eventos cardíacos mayores en DM asintomáticos estudiados con SPECT miocárdico en esfuerzo. Método: Se estudiaron 40 pacientes asintomáticos coronarios, con DM conocida por >5 años, >45 años de edad, con >2 factores de riesgo cardiovascular (FRCV) y electrocardiograma basal normal o con alteraciones inespecíficas. Todos efectuaron una prueba de esfuerzo (PE) adecuada y se estudiaron con Sestamibi-Tc99m repetido en 32 casos al 3° año. Además, se evaluó a 36 controles no diabéticos con >2 FRCV. El seguimiento fue de 64+/-11 meses. Resultados: En el grupo DM, 48 por ciento tenía Hba1c>7.5 por ciento; en ellos el SPECT mostró isquemia silente (IS) en 30 por ciento y la PE en 18 por ciento del total. No hubo variaciones significativas en SPECT al 3° año. Hubo una muerte no cardíaca en el 2° año; en el 4° año, se produjo una muerte por infarto agudo de miocardio, con mínima isquemia septal y otra asociada a miocardiopatía e insuficiencia cardíaca, con defecto de predominio fijo, ambos con PE negativa. En el grupo control, el 11 por ciento tuvo SPECT anormal y 8 por ciento PE positiva; hubo una muerte no cardíaca. El Odds Ratio para isquemia fue 3.42 [IC=0.99-11.85] entre DM vs controles y el Hazard Ratio para eventos cardíacos 6.75 [IC=0.40-108.2]. Conclusiones: En DM asintomáticos coronarios el riesgo de IS en SPECT fue mayor que en controles sin DM y con FRCV. Los eventos cardiacos mayores fueron más frecuentes, aunque no significativamente, en DM que en controles. Ello deberá reevaluarse conocidos los resultados del estudio multicéntrico.

The clinical value of myocardial perfusion studies in cardiac asymptomatic patients with Diabetes Mellitus (DM) is controversial. Aim: To conduct a 5 year follow-up study to detect major adverse cardiac events in asymptomatic DM patients using exercise stress and SPECT myocardial perfusion imaging. Methods: 40 patients with known DM for at least 5 years and without evidence of coronary artery disease, older than 45 years of age with >2 cardiovascular risk factors (CVRF) and either normal or minimally altered ECG underwent adequate exercise testing (ET) and 99mTc Sestamibi, repeated 3 years later in 32 cases. We also assessed 36 non-diabetic control patients, with >2 CVRF. Mean follow up was 64+/-11 months. Results: 48 percent of DM patients had HbA1c >7.5 percent; in them, the SPECT showed silent ischemia (SI) in 30 percent and positive ET in 18 percent. There were no significant variations in SPECT at 3 years. There was 1 non-cardiac death in the 2nd year and 2 deaths, one from acute myocardial infarction associated to minimal septal ischemia and another associated with cardiomyopathy and heart failure, with a fixed perfusion defect. Both patients had a negative ET. In the control group, 11 percent had abnormal SPECT and 8 percent positive ET and no cardiac deaths were observed. The Odds ratio for ischemia between DM and controls was 3.42 [CI=0.99-11.85 ] and the Hazard Ratio for cardiac events was 6.746 [CI=0.4205-108.2]. Conclusions: In asymptomatic coronary DM patients, the presence of SPECT ischemia detect was higher than in non-DM controls with CVRF. The incidence of major cardiac events was higher, although not significantly, in DM than control patients. This finding should be re-evaluated in the multicenter study.

Cuantificación paramétrica de los cambios en la perfusión cerebral producidos por abstinencia y con activación neurocognitiva en dependientes de cocaína / Changes in cerebral perfusion caused by abstinence in cocaine-dependent patients

Introducción. Los sujetos dependientes de cocaína pueden presentar deterioro neurocognitivo y alteraciones conductuales con importantes implicancias sociales. En esos pacientes se han demostrado diversas anormalidades en la perfusión cerebral, especialmente en la corteza prefrontal. Esta región cortical está relacionada con funciones ejecutivas y con el control de impulsos. El Wisconsin Card Sorting Test (WCST) fue diseñado específicamente para activar la corteza prefrontal. Objetivo. En sujetos dependientes de cocaína, cuantificar cambios en la perfusion cerebral basal y post activación con WCST inducidos por la detoxificación. Método. Se estudió a 23 pacientes entre 24 y 49 años de edad (19 hombres) que cumplían criterios DSM-IV para dependencia de cocaína y con consumo reciente demostrado. En todos ellos se obtuvo SPECT de perfusión cerebral en condiciones de reposo al ingreso y tras 4 semanas de hospitalización con abstinencia controlada. En 19 sujetos se realizó además SPECT cerebral con activación usando WCST, al inicio y al final de la hospitalización. Para comparar estas cuatro condiciones se utilizó Statistical Parametric Mapping (SPM). Resultados. Al comparar la perfusión en condiciones de reposo inicial y al mes de abstinencia se observó mejoría significativa de múltiples áreas corticales especialmente en región parieto-occipital bilateral y corteza prefrontal izquierda.El análisis grupal no demostró activación de corteza prefrontal con WCST al ingreso a la terapia de detoxificación. Luego de 4 semanas de abstinencia estricta, se observó significativa activación post WCST de corteza prefrontal dorsolateral izquierda.Conclusiones. Un mes de abstinencia estricta de cocaína produce mejoría de la perfusión cerebral en pacientes dependientes. Post consumo reciente, no se demuestra activación a nivel prefrontal con el estímulo del WCST, la cual se observa luego de abstinencia, lo que indica mejoría neurocognitiva...

Introduction. Cocaine-dependent subjects might have socially disruptive behavior. Several regional cerebral blood flow (rCBF) abnormalities have been described in these patients, mainly in the prefrontal cortex, area related to executive functions and impulse control. Wisconsin Card Sorting Test (WCST) was specifically designed to activate this cortical area. Aim. To quantify rCBF and to assess prefrontal activation pre and post detoxification on cocaine-dependant subjects. Methods. We studied 23 patients who met DSM-IV criteria for cocaine dependency ranging from 24 - 49 years old (19 males), all with positive urine cocaine test. Baseline 99mTc-ECD brain perfusion SPECT was performed at admission and after 4 weeks of controlled in-hospital abstinence; in 19 patients SPECT was acquired also after WCST activation. Statistical Parametric Mapping (SPM) was used to compare SPECT studies on these 4 conditions. Results. rCBF of bilateral parieto-occipital area, left prefrontal cortex and multiple small cortical region improved after 4 weeks of cocaine detoxification. The group analysis did not show significant prefrontal cortex activation induced by WCST on admission. After 4 weeks of strict cocaine abstinence, WCST was able to induce left dorsolateral prefrontal cortex activation. Conclusions. A month of strict cocaine abstinence improved brain perfusion in dependant patients. After recent consumption, there was no prefrontal activation when using WCST, but this was observed after abstinence, supporting neurocognitive improvement. These findings may have clinical implications as potential predictors of therapy response.

Brain perfusion abnormalities associated to drug abuse in recent abstinent patients using SPECT 99m Tc-ethylen-cysteinate-dimer (ECD)

Several substances may produce brain perfusion abnormalities in drug-dependent patients. Their mechanism is unclear and several causes might be involved, especially vasospasm in cocaine consumption. Goal: To characterize residual brain perfusion abnormalities in substance-dependent population. We analyzed brain perfusion in 100 dependant patients (DSM-IV criteria) following a month of strict in-hospital abstinence (age:35 +/- 2y.o.; 86 percent men); 55 percent corresponded to poly-drug dependents, mainly to cocaine, alcohol and cannabis; 44 percent mono-drug users, mostly to alcohol. Results: Single Photon Emission Computed Tomography (SPECT) with 99mTc-ethylen-cysteinate-dimer (ECD) was abnormal in 54 percent of the cases, with bilateral cortical hypo-perfusion in 89 percent, focal in 54 percent and diffuse in 46 percent of them, with moderate or severe intensity in 61 percent. The abnormal perfusion group’s age was 38 +/- 12 versus 31 +/- 10 years in the normal SPECT group (P=0.005) with a consumption period of 16 +/- 11 versus 11 +/- 8 years, respectively (P=0.043). Only 29 percent of women had abnormal perfusion versus 58 percent of men (P=0.047). Abnormal brain perfusion in 64 percent of mono and 45 percent in poly-drug dependents (P=0.07). Psychometric tests performed in 25 patients demonstrated association between perfusion defects and cognitive abnormalities. Relative risk for abnormal psychometric test was 2.5 [95 percent;CI=1.1-5.6] for abnormal SPECT. Conclusion: Dependent population after a month of abstinence persists with cortical brain perfusion abnormalities, associated to age, sex and type of drug consumption.

Utilidad del gatillado precoz en SPECT de percusión miocárdica con tecneciados y vasodilatadores: problemas inherentes y análisis de experiencia preliminar local / Usefulness of gated myocardial perfusion SPECT imaging with technetium and vasodilators

En enfermedad coronaria (EC) severa por disfunción transitoria del ventrículo izquierdo (VI) se puede observar dilatación cavitaria e incremento en la captación pulmonar del radiofármaco mediante imágenes de perfusión miocárdica, descrito inicialmente con 201Talio en estrés. La isquemia inducida por dipiridamol (DIP) que es controvertida, en cuanto a su mecanismo, también puede disminuir la función sistólica. La fracción de eyección ventricular izquierda (FEVI) post estrés puede no pesquisar esta alteración, dependiendo del momento de inicio de la adquisición gatillada. Hay diversas publicaciones al respecto con diferentes resultados. Objetivos: Evaluar la correlación de parámetros funcionales del VI e isquemia en SPECT gatillado precoz usando perfusión miocárdica en pacientes referidos para evaluación de EC. Además, se decidió revisar ampliamente las dificultades del protocolo. Método: De 158 pacientes evaluados inicialmente, se excluyó 31 por ciento por presencia de actividad extra cardiaca que interfería con la delimitación automática de bordes. El grupo analizado incluyó 109 sujetos entre 33 y 91 años (promedio 64,3 + - 11,7), 52 por ciento de mujeres. Treinta de ellos con EC conocida; 18 con infarto de miocardio y 31 con isquemia en imágenes de perfusión. El estudio tomográfico SPECT 99mTc-Sestamibi fue efectuado durante los 60 min post DIP, con protocolo de 1 día. Se usó programa Cedars QGS y QPS para FEVI, volúmenes y cálculo de dilatación isquémica transitoria (DIT) en imágenes de fin de diástole. También se calculó índice pulmón/corazón (IPC) de imágenes SPECT. Resultados: El lapso promedio entre inyección estrés y adquisición fue 27 min (rango: 18-43). No hubo diferencia significativa entre FEVI post DIP y reposo (66,55 + -17,33 por ciento versus 67,58 + - 18,41 por ciento, con delta FEVI: 1,03 + - 6,72 por ciento). Tampoco hubo correlación de los parámetros analizados en globo según presencia de isquemia, infarto o EC. Sólo se encontró diferencias...

Using myocardial perfusion studies, severe coronary artery disease (CAD) with left ventricular dysfunction could be observed through transient cavity dilation and radiopharmaceutical lung uptake increase, described initially with stress 201Tl. Dipyridamole (DIP) induced ischemia also can diminish systolic function. Delayed post stress left ventricular ejection fraction (FEVI) may not be able to detect this phenomena, depending on the acquisition timing. There are diverse reports and results in this issue. Goal: Evaluate the correlation between left ventricular parameters and ischemia presence in early gated DIP tomography in patients referred for CAD evaluation along to review the new protocol difficulties.Methods: From 158 patients evaluated initially, 31% presenting extra-cardiac activity were excluded due to interference with automatic edge detection. The analyzed group included 109 subjects between 33 and 91 years, mean age 64.3 ± 11.7; 52% women. Thirty of them were known CAD patients; 18 with myocardial infarction and 31 with ischemia in perfusion images. 99mTc-Sestamibi SPECT was carried out during the 60 min post DIP infusion, using 1 day protocol. Cedars QGS QPS Programs were used to measure LVEF and left ventricular volumes. Diastolic transient ischemic dilation (TID) calculation was performed as well as lung/heart index (LHR). Results: The mean time lapse between DIP injection and acquisition was 27 min (range: 18-43 min). There was not significant difference between DIP and rest LVEF (66.55±17.33% vs 67.58±18.41%) LVEF delta was 1.03±6.72%. There was not correlation observed between measured functional parameters and presence of ischemia, infarction or known CAD. There was clear difference in left ventricular volumes in patients with and without CAD and known myocardial infarction. Conclusion: Nor association between LHR, LVEF delta or TID and ischemia was demonstrated in early post DIP...

Evaluación con imágenes en fibrodisplasia osificante progresiva (FOP): caso clínico pediátrico / Imaging evaluation of fibrodysplasia ossificans progressiva (FOP): pediatric case

Se revisa el tema de fibrodisplasia osificante progresiva (FOP), que es una enfermedad autosómica dominante infrecuente a propósito de un caso pediátrico. El cuadro debuta como aumento de volumen transitorio y fluctuante en extremidades superiores y es estudiado con diversas imágenes radiológicas e isotópicas. Se discute la patogenia, presentación clínica y terapia así como la utilidad relativa de las diferentes técnicas diagnósticas en la caracterización de la enfermedad.