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San José Hospital. Azogues- Ecuador, Prólogo Quince años. Una década y media marcada por el pulso firme de la dedicación, la pasión y el compromiso con la salud y el bienestar de nuestra comunidad. Quince años de servicio médico ininterrumpido, donde cada día ha sido un desafío, una oportunidad para aprender, crecer y, sobre todo, para salvar vidas. El Hospital San José de Azogues, epicentro de atención médica en nuestra provincia de Cañar, ha sido testigo de incontables historias de esperanza, valentía y resiliencia. En sus pasillos, salas de emergencia y quirófanos, se ha forjado un legado de excelencia clínica, humanidad y compromiso con el prójimo. Este libro, "Temas de Guardia en Emergencias Médicas", surge como un testimonio palpable de ese compromiso. Es una recopilación de conocimientos, experiencias y enseñanzas adquiridas a lo largo de estos quince años de arduo trabajo. Es el reflejo de la dedicación incansable de un equipo multidisciplinario de profesionales de la salud, comprometidos con brindar la mejor atención incluso en las circunstancias más desafiantes. En estas páginas, encontrarán una síntesis de las situaciones más frecuentes y críticas que enfrentamos en nuestra guardia médica. Se incluyen los siguientes apartados clínico-quirúrgicos: cuerpo extraño en el aparato digestivo, apendicitis aguda, embarazo ectópico, mastitis, fracturas mandibulares, cetoacidosis diabética, síndrome de Dress, manejo de quemaduras en niños, trauma craneoencefálico, manejo de choque hipovolémico, hemorragia digestiva alta, hipertensión arterial, miomatosis uterina e insuficiencia renal. Estos temas relevantes se presentan en el primer volumen de esta invaluable obra, preparada por médicos tratantes y residentes de nuestro hospital. Además, contamos con la contribución de colegas y catedráticos de nuestra región, quienes han aportado capítulos fundamentales que complementan la diversidad de conocimientos aquí reunidos. Cada capítulo no solo aborda los aspectos clínicos y terapéuticos de estas patologías

Prólogo Quince años. Una década y media marcada por el pulso firme de la dedicación, la pasión y el compromiso con la salud y el bienestar de nuestra comunidad. Quince años de servicio médico ininterrumpido, donde cada día ha sido un desafío, una oportunidad para aprender, crecer y, sobre todo, para salvar vidas. El Hospital San José de Azogues, epicentro de atención médica en nuestra provincia de Cañar, ha sido testigo de incontables historias de esperanza, valentía y resiliencia. En sus pasillos, salas de emergencia y quirófanos, se ha forjado un legado de excelencia clínica, humanidad y compromiso con el prójimo. Este libro, "Temas de Guardia en Emergencias Médicas", surge como un testimonio palpable de ese compromiso. Es una recopilación de conocimientos, experiencias y enseñanzas adquiridas a lo largo de estos quince años de arduo trabajo. Es el reflejo de la dedicación incansable de un equipo multidisciplinario de profesionales de la salud, comprometidos con brindar la mejor atención incluso en las circunstancias más desafiantes. En estas páginas, encontrarán una síntesis de las situaciones más frecuentes y críticas que enfrentamos en nuestra guardia médica. Se incluyen los siguientes apartados clínico-quirúrgicos: cuerpo extraño en el aparato digestivo, apendicitis aguda, embarazo ectópico, mastitis, fracturas mandibulares, cetoacidosis diabética, síndrome de Dress, manejo de quemaduras en niños, trauma craneoencefálico, manejo de choque hipovolémico, hemorragia digestiva alta, hipertensión arterial, miomatosis uterina e insuficiencia renal. Estos temas relevantes se presentan en el primer volumen de esta invaluable obra, preparada por médicos tratantes y residentes de nuestro hospital. Además, contamos con la contribución de colegas y catedráticos de nuestra región, quienes han aportado capítulos fundamentales que complementan la diversidad de conocimientos aquí reunidos. Cada capítulo no solo aborda los aspectos clínicos y terapéuticos de estas patologías

Background: The crista terminalis (CT) has been identified as the posterior boundary of typical atrial flutter (AFL) in the lateral wall (LW) of the right atrium (RA). To study conduction properties across the CT, rapid pacing was performed at both sides of the CT after bidirectional conduction block was achieved in the cavotricuspid isthmus by radiofrequency catheter ablation. Methods and results: In 22 patients (aged 61+/-7 years) with AFL (cycle length, 234+/-23 ms), CT was identified during AFL by double electrograms recorded between the LW and posterior wall (PW). After the ablation procedure, decremental pacing trains were delivered from 600 ms to 2-to-1 local capture at the LW and PW or coronary sinus ostium (CSO). At least 5 bipolar electrograms were recorded along the CT from the high to the low atrium next to the inferior vena cava. No double electrograms were recorded during sinus rhythm in that area. Complete transversal conduction block all along the CT (detected by the appearance of double electrograms at all recording sites and craniocaudal activation sequence on the side opposite to the pacing site) was observed in all patients during pacing from the PW or CSO (cycle length, 334+/-136 ms), but it was fixed in only 4 patients. During pacing from the LW, complete block appeared at a shorter pacing cycle length (281+/-125 ms; P<0.01) and was fixed in 2 patients. In 3 patients, complete block was not achieved. Conclusions: These data suggest the presence of rate-dependent transversal conduction block at the crista terminalis in patients with typical AFL. Block is usually observed at longer pacing cycle lengths with PW pacing than with LW pacing. This difference may be a critical determinant of the counterclockwise rotation of typical AFL, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: The FIRE AND ICE trial assessed efficacy and safety of pulmonary vein (PV) isolation using cryoballoon versus radiofrequency current (RFC) ablation in patients with drug refractory, symptomatic, paroxysmal atrial fibrillation (AF). The purpose of the current study was to assess index lesion durability as well as reablation strategy and outcomes in trial patients undergoing a reablation procedure. Methods: Patients with reablation procedures during FIRE AND ICEwere retrospectively consented and enrolled at 13 trial centers. The first reablation for each patient was included in the analysis. Documented arrhythmias before reablation, number and location of reconnected PVs, lesions created during reablations, procedural characteristics, and acute as well as long-term outcomes were assessed. Results: Eighty-nine (36 cryoballoon and 53 RFC) patients were included in this study. Paroxysmal atrial fibrillation was the predominant recurrent arrhythmia (69%) before reablation. Reablations occurred at a median of 173 and 182 days (P=0.54) in the cryoballoon and RFC cohorts, respectively. The number of reconnected PVs was significantly higher in the RFC than the cryoballoon group (2.1±1.4 versus 1.4±1.1; P=0.010), which was driven by significantly more reconnected left superior PVs and markedly more reconnected right superior PVs. The number of (predominantly RFC) lesions applied during reablation was significantly greater in patients originally treated with RFC (3.3±1.3 versus 2.5±1.5; P=0.015) with no difference in overall acute success (P=0.70). After reablation, no differences in procedure-related rehospitalization or antiarrhythmic drug utilization were observed between cohorts. Conclusions: At reablation, patients originally treated with the cryoballoon had significantly fewer reconnected PVs, which may reflect RFC catheter instability in certain left atrial regions, and thus required fewer lesions for reablation success. Repeat ablations were predominantly pe, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging requires novel and time-efficient approaches to characterize the myocardial substrate associated with ventricular arrhythmia in patients with ischemic cardiomyopathy. Using a translational approach in pigs and patients with established myocardial infarction, we tested and validated a novel 3D methodology to assess ventricular scar using custom transmural criteria and a semiautomatic approach to obtain transmural scar maps in ventricular models reconstructed from both 3D-acquired and 3D-upsampled-2D-acquired LGE-CMR images. The results showed that 3D-upsampled models from 2D LGE-CMR images provided a time-efficient alternative to 3D-acquired sequences to assess the myocardial substrate associated with ischemic cardiomyopathy. Scar assessment from 2D-LGE-CMR sequences using 3D-upsampled models was superior to conventional 2D assessment to identify scar sizes associated with the cycle length of spontaneous ventricular tachycardia episodes and long-term ventricular tachycardia recurrences after catheter ablation. This novel methodology may represent an efficient approach in clinical practice after manual or automatic segmentation of myocardial borders in a small number of conventional 2D LGE-CMR slices and automatic scar detection., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Pacing and Beta-Blockers in Repetitive Polymorphic VT. An 18-year-old woman presented with recurrent exercise-induced syncopal episodes and severe systolic dysfunction. ECG monitoring disclosed repetitive polymorphic ventricular complexes, paroxysms of bidirectional ventricular tachycardia, and nonsustained bursts of slow polymorphic ventricular tachycardia that increased in length and rate during exercise. Ventricular arrhythmias were refractory to medical treatment, which included verapamil and beta-blockers. Addition of permanent atrial pacing to beta-blocker therapy suppressed the arrhythmias and reversed systolic impairment in the following months., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Objective: Bone loss and bone fractures are disabling complications after heart transplantation. Severe bone loss happens mainly during the first year posttransplantation. Steroids and cyclosporine alter bone metabolism in several ways. To counterbalance these effects, antiresorptive therapy is provided to these patients. The objective of this study was to assess the frequency of bone fractures after heart transplantation, considering previous comorbidities, immunosuppressive therapy, and osteoprotective treatment. Methods: From 1993 to 2005, 443 consecutive heart transplant recipients were followed for the occurrence of bone fractures, immunosuppressive therapy, clinical conditions, and antiresorptive treatment. Results: There were 41 fractures in 34 patients (7.6%, group I). The remainder of patients formed group II. Fractures commonly involved the lumbar spine. Postmenopausal women had more fractures than other patients (20.6% vs 7.8%, P = .02). When the initial immunosuppressive regimen included tacrolimus, fractures did not happen (P = .01, vs other regimens). Osteoprotective therapy was administered to 91.2% of patients in group I and 79% in group II (P = .08). Mean interval from transplantation to the first fracture was 1131.5 days. Overweight patients had a 61.8% incidence of fracture. Conclusions: Our series showed a low frequency of bone fractures. Postmenopausal women and overweight patients had more fractures. An initial immunosuppressive regimen using tacrolimus was associated with lower fracture rates., Depto. de Fisiología, Fac. de Medicina, TRUE, pub

We report an arrhythmic complication in two patients in whom a procedure directed at isolating one or two pulmonary veins had been performed. The complication was related to pulmonary vein disconnection scars after ablation. Both patients developed new clinical tachycardia (atypical atrial flutter) secondary to a reentrant phenomena in the vicinity of a previously ablated pulmonary vein., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Epicardial Connections Between PVs and the LA. Introduction: Some observations support the existence of epicardial connections (ECs) between ipsilateral pulmonary veins (vein to vein ECs [VVECs]), and we have observed venoatrial ECs inserted at distance from the pulmonary vein ostium (vein to atrium ECs [VAECs]). Our aim was to determine the prevalence of ECs and their relevance for pulmonary vein isolation. Methods and Results: We studied 100 consecutive patients with drug-refractory atrial fibrillation who underwent ostial pulmonary vein isolation by cooled radiofrequency catheter ablation. A VVEC was identified if pulmonary vein pacing activated the ipsilateral vein before the atrium, requiring ablation of both venous ostia to isolate either pulmonary vein. A VAEC was identified if pacing produced atrial breakthrough located at distance from the venous ostium, requiring extraostial ablation to isolate the pulmonary vein. Patients with ECs (20%) were younger (P = 0.02) and had a higher prevalence of structural heart disease (P = 0.01) than patients without ECs. VVECs and VAECs were identified in 32 pulmonary veins (10%) and VAECs in 10 veins (3%). Veins with ECs had a higher rate of early recurrence of conduction following isolation (29% vs 11%; P = 0.01). Conclusion: Twenty percent of patients with atrial fibrillation had ECs resistant to ostial ablation in one or more pulmonary veins. Isolating veins with ECs may require a different ablation approach. These connections are associated with an increased rate of early recurrence of conduction., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: A key point in atrial fibrillation (AF) ablation is the ability to identify the pulmonary vein (PVs) and locate their ostia. Objectives: The purpose of this study was to assess the error margin of PV identification and ostia location in the absence of previous PV imaging. Methods: This study was performed in patients referred for catheter ablation of AF. PVs were reconstructed before ablation using the CARTO system. The operator tagged the superior and inferior edges of the PV ostia before and after examining the corresponding PV angiograms. The distances between the tagged PV ostia were measured using CARTO software. Results: A total of 105 location estimations of 54 PVs were analyzed. The location of PV ostia without angiography deviated from the angiographic PV ostia by a median of 13 mm (95% confidence interval = 11-14 mm; P < .0001). In 84 of the 105 estimations (80%), wrong tagging was performed inside the PV. A multiple logistic regression revealed that, at sites displaying PV potentials, the left atrial potential amplitude was an independent predictor of location at the angiographic PV ostium (odds ratio 24 [95% confidence interval = 3.7-227] per 1-mV increase). Receiver operator characteristic analysis set the optimal cutoff level at 0.7 mV. Use of this criterion improved the accuracy of PV ostium location by 4 mm (95% confidence interval = 1-6 mm; P = .005). Conclusion: Attempts at PV identification and ostia location in the absence of previous PV imaging are subject to a broad error margin, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Referencias bibliográficas: • Azcoaga, J.E. (1979). Aprendizaje fisiológico y aprendizaje pedagógico. Buenos Aires: Paidós. • Bellinger, D. C., & Newburguer, J.W. (2010). Neuropsychological, psychosocial, and quality-of-life outcomes in children and adolescents with congenital heart disease. Prog Pediatr Cardiol, 29(2), 87-92. https://doi.org/10.1016/j.ppedcard.2010.06.007 • Bellinger, D.C., Wypij, D., duPlessis, A.J., Rappaport, L.A., Jonas, R.A., Wernovsky, G., & Newburguer, J.W. (2003). Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg, 126(5), 1385-96. https://doi.org/10.1016/s0022-5223(03)00711-6 • Bishop, D. (2006). What causes specific language impairment in children? Current Directions in Psychological Science, 15 (5), 217–221. https://dx.doi.org/10.1111%2Fj.1467-8721.2006.00439.x • Blair, C., & Razza, R.P. (2007). Relating effortful control, executive function, and false belief understanding to emerging match and literacy ability in kindegarten. Child Development, 78(2), 647-663. https://doi.org/10.1111/j.1467-8624.2007.01019.x • Calderon, J., Bonnet, D., Courtin, C., Concordet, S., Plumet, M., & Angeard, N. (2010). Executive function and theory of mind in school-aged children after neonatal corrective cardiac surgery for transposition of the great arteries. Dev Med Child Neurol, 52 (12), 1139-1144. https://doi.org/10.1111/j.1469-8749.2010.03735.x • Calderon, J., Angeard, N., Moutier, S., Plumet, M.H., Jambaqué, I., & Bonnet, D. (2012). Impact of prenatal diagnosis on neurocognitive outcomes in children with transposition of the great arteries. The Journal of Pediatrics, 161(1), 94-98. https://doi.org/10.1016/j.jpeds.2011.12.036 • Cassidy, A.R., White, M.T., DeMaso, D.R., Newburguer, J.W., & Bellinger, D.C. (2014). Executive function in children and adolescents with critical cyanotic congenital heart disease. J Int Neuropsychol Soc, 21(1), 34-49, Las cardiopatías congénitas (CC) constituyen una de las principales causas de mortalidad en España. Se quiere identificar la existencia de (co)morbilidades en el neurodesarrollo de estos menores para evidenciar la necesidad de participar en programas de Atención Temprana (AT) para optimizar su desarrollo y al mismo tiempo ofrecer una revisión sistemática a modo de estado de la cuestión de este campo de intervención. Se valoró, con la Escala de Desarrollo Infantil Bayley-III, a infantes cardiópatas ( 25 meses), en el Hospital Universitario La Paz, en el Hospital 12 de Octubre y en la Fundación Menudos Corazones. Se describen las características biomédicas y de desarrollo de 90 participantes. El 68% presenta un desarrollo cognitivo dentro del promedio, sucediendo lo mismo en el área del lenguaje (42%) y motor (44%). En estas últimas se evidencia un desarrollo normal-lento (35% y 24%, respectivamente) y limítrofe (15% y 12%). La revisión realizada de la literatura científica al respecto corrobora que tanto el área comunicativa-lingüística como la motora son las dimensiones del desarrollo que presentan necesidades., Congenital Heart Disease (CHD) is one of the leading causes of mortality in Spain. This study aims (i) to identify the existence of (co)morbidities in the neurodevelopment of a sample of these children and (ii) to demonstrate the need for them to receive educational intervention as soon as possible through early care programs so that their maturational development can be optimized. This study also presents a systematic review of the research available in the field. With the Bayley-III Child Development Scale, cardiac infants (M = 25.3 months) at the University Hospital La Paz, at the Hospital 12 de Octubre and the Menudos Corazones Foundation were assessed. The biomedical and developmental characteristics of 90 participants are described. 68% have an average cognitive development. Average rates were also reported for linguistic (42%) and motor (44%) development. For the latter category, normal-slow (35% and 24%, respectively) and bordeline (15% and 12%) development rates were found. The review of the scientific literature in this regard corroborates that the communicative-linguistic and the motor areas are the poorest dimensions of development., Les cardiopathies congénitales (CHD) sont l’une des principales causes de mortalité en Espagne. Cette étude vise à identifier l’existence de (co)morbidités dans le développement neurologique de ces enfants afin d’identifier et de démontrer la nécessité de recevoir une intervention éducative le plus tôt possible à travers des programmes d’intervention précoce (IPE) pour optimiser leur développement maturatif et en même temps d’offrir une revue systématique comme état de l’art dans ce domaine d’intervention. Les nourrissons cardiopathes (M = 25,3 mois) ont été évalués à l’aide de l’échelle de développement de l’enfant Bayley-III à l’Hospital Universitario La Paz, l’Hospital 12 de Octubre et la Fundación Menudos Corazones. Les caractéristiques biomédicales et de développement de 90 participants sont décrites. Le développement cognitif se situait dans la moyenne dans 68 % des cas, et il en allait de même pour le langage (42 %) et les capacités motrices (44 %). Chez ces derniers, on constate un développement normal-lent (35% et 24%, respectivement) et limite (15% et 12%). La revue de la littérature scientifique effectuée à cet égard corrobore que les domaines communicatif-linguistique et moteur sont les dimensions du développement qui présentent des besoins., Depto. de Estudios Educativos, Fac. de Educación, TRUE, pub

Background: RS morphology of the unipolar electrogram is associated with propagation of the wave front through the exploring electrode, whereas positive uniphasic (R) unipolar electrograms are characteristic of the end of activation. Methods and results: Unipolar electrograms were recorded in 45 consecutive patients with atrial flutter who were undergoing radiofrequency ablation (RFA). Bidirectional cavotricuspid isthmus (CTI) block was achieved in 44 patients. The unipolar electrogram obtained before RFA at the low anterolateral right atrium during coronary sinus pacing changed from RS, rS, or QS to R or Rs in all patients after clockwise CTI block was obtained. The morphology of unipolar electrograms recorded close to the coronary sinus during pacing from the low anterolateral right atrium changed from RS or rS to R or Rs in all but 4 patients after counterclockwise CTI block. In the patient in whom CTI block was not achieved, the RS morphology of the unipolar electrogram remained unchanged. In 18 patients, the results of the RFA were assessed with only the unipolar electrogram. The unipolar electrogram correctly predicted 100% and 89% of the cases of clockwise and counterclockwise CTI block, respectively. Conclusions: The creation of CTI block is associated with an easily detectable loss of negative components and development of an R or Rs pattern of the unipolar electrogram recorded close to the ablation line while pacing at the opposite side of the CTI., Depto. de Medicina, Fac. de Medicina, TRUE, pub

En el momento de la publicación de este artículo (año 2019), la revista Salud, Bienestar y Sociedad estaba indexada en ROAD., Las cardiopatías congénitas (CC) son defectos estructurales del corazón que están presentes en el feto y en el recién nacido; son una de las principales causas de mortalidad infantil en España, y la mayor parte requieren cirugía por circulación extracorpórea (CEC) en el primer año de vida, pudiendo presentar mayor riesgo neurológico. El objetivo de este estudio cuantitativo ―transversal y multicéntrico― es identificar si la durabilidad de la CEC, como parámetro biomédico, repercute en su neurodesarrollo. Se presenta una muestra total N=70, con CC, sin anomalías cromosómicas asociadas, valorada mediante la Escala de Desarrollo Bayley-III, en la Fundación Menudos Corazones, el Hospital U. La Paz de Madrid y el Hospital 12 de Octubre. Para comprobar si la duración (en minutos) de la CEC repercute en las áreas del desarrollo, se realizó un análisis descriptivo en cinco periodos (<60, 61-120, 121-180, 181-241, >242). Los resultados muestran que los participantes cuya intervención fue >242 minutos obtienen lentificaciones a nivel motor (75,5), en el lenguaje (84,5) y a nivel cognitivo (86,6), mientras que el neurodesarrollo de aquellos cuya duración fue <60 se sitúa dentro del promedio (103; 92; 98,3), respectivamente. En el resto se observa un desarrollo normal-lento en el lenguaje y motor (181-241: 85,2- 89,1; 121-180: 87,7-86,5, correspondientemente), excepto en la franja de 61-120 minutos, donde se aprecia lentificación en el lenguaje (87,5). Como conclusión, señalar que la duración de la intervención quirúrgica mediante CEC repercute negativamente en el desarrollo del infante pues a mayor tiempo quirúrgico, peores resultados en las áreas del neurodesarrollo., Congenital heart disease (CHD) are structural defects of the heart that are present in the fetus and in the newborn; they are one of the main causes of infant mortality in Spain, and most require surgery for cardiopulmonary bypass (CEC) in the first year of life, and may present a greater neurological risk. The aim of this quantitative study -transverse and multicentre- is to identify whether the durability of the CEC, as a biomedical parameter, affects its neurodevelopment. A total sample N= 70 is presented, with CC, without associated chromosomal abnormalities, assessed by the Bayley-III Development Scale, at the Menudos Corazones Foundation, the U. La Paz Hospital in Madrid and the Hospital 12 de Octubre. To verify whether the duration (in minutes) of the CEC affects the areas of development, a descriptive analysis was carried out in five periods (<60, 61-120, 121-180, 181-241, >242). The results show that participants whose intervention was >242 minutes obtained slows at motor level (75.5), in language (84.5), and cognitive level (86.6), while neurodevelopment of those whose duration was <60 is within the average (103; 92; 98.3), respectively. In the rest, a normal-slow development is observed in the language and motor (181-241: 85.2- 89.1; 121-180: 87.7-86.5, correspondingly), except in the strip 61-120 minutes, where language slows down (87.5). In conclusion, it should be noted that the duration of the surgical intervention by means of CEC has a negative impact on the development of the infant, since the longer the surgical time, the worse the results in the neurodevelopment areas., Depto. de Estudios Educativos, Fac. de Educación, TRUE, pub

El procedimiento estándar de selección de pacientes con hipertensión arterial (HTA) esencial en los ensayos clínicos de los tratamientos antihipertensivos puede incluir pacientes con HTA clínica aislada (HTA-CA) o de bata blanca, lo cual amenaza su validez. Utilizando mediciones clínicas (procedimiento estándar) y automediciones de la presión arterial (PA), se estimó la prevalencia de HTA-CA entre 43 varones con HTA esencial participantes en un ensayo controlado sobre entrenamiento en control de estrés. El error diagnóstico debido a la presencia de HTACA osciló entre 28% y 55%. Tras reanalizar los datos de eficacia del ensayo en función del tipo de HTA se encontró que la presencia de HTA-CA sobreestima la reducción observada en la PA sistólica clínica, pero no en la automedida ni en la PA diastólica clínica o automedida. Se concluye que el procedimiento estándar de selección de pacientes con HTA esencial debe complementarse con medidas no clínicas de PA (automediciones o medidas ambulatorias)., In clinical trials on antihypertensive treatments, the standard procedure to select patients with essential hypertension (EH) may involve the admission of patients with white-coat or isolated clinical hypertension (ICH) that threats trial validity. Employing clinic blood pressure (BP) measurements (standard procedure) and BP self-measurements, the present study estimated the prevalence of ICH among 43 males with EH who had participated in a controlled trial on stress-management training. Diagnostic errors due to the inclusion of ICH ranged from 28% to 55%. After re-analyzing data on efficacy taking into account the type of hypertension, the results suggested that the inclusion of ICH leads one to overestimate the reductions of clinic systolic BP found at postreatment but not those of clinic diastolic BP or self-measured BP. It was concluded that the standard procedure of selection of EH patients should be supplemented by other BP measures taken outside clinic (e.g., self-measurements or ambulatory recordings)., Comunidad de Madrid, Depto. de Personalidad, Evaluación y Psicología Clínica, Fac. de Psicología, TRUE, pub

Background: Ablation of some myocardial substrates requires catheter-based radiofrequency delivery at the root of a great artery. We studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. Methods: Thirty-six pigs underwent in-vivo catheter-based ablation under continuous contact-force and lesion index (power, contact-force, and time) monitoring during 60-s radiofrequency delivery with an open-irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 W (n=9), 50 W (n=10), or 60 W (n=9) radiofrequency energy, and acute (n=22) and chronic (n=6) arterial wall damage was quantified by multiphoton microscopy in ex vivo samples. Adjacent myocardial lesions were quantified in parallel samples. The remaining 8 pigs were used to validate safety and efficacy parameters. Results: Acute collagen and elastin alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in lesions without steam pop. The main parameters associated with steam pops were median peak temperature >42°C and impedance falls >23 ohms. Unlike other parameters, lesion index values of 9.1 units (interquartile range, 8.7-9.8) were associated with the presence of adjacent myocardial lesions in both univariate ( P=0.03) and multivariate analyses ( P=0.049; odds ratio, 1.99; 95% CI, 1.02-3.98). In the validation group, lesion index values using 40 W over a range of contact-forces correlated with the size of radiofrequency lesions (R2=0.57; P=0.03), with no angiographic or histopathologic signs of coronary artery damage. Conclusions: Lesion index values obtained during 40 W radiofrequency applications reliably monitor safe and effective lesion creation at the root of the great arteries., Fundación Interhospitalaria para la Investigación Cardiovascular, Sociedad Española de Cardiología, Fondo Europeo de Desarrollo Regional, Ministerio de Ciencia, Innovación y Universidades, Depto. de Medicina, Fac. de Medicina, TRUE, pub

There is interest to analyse newer biomarkers to identify healthy individuals at risk to develop cardiovascular disease (CVD) incidents and death. To determine in healthy individuals new circulating protein biomarkers, whose systemic levels may be associated with the risk of future development of CVD incidents and death. The study was performed in 82 individuals from the Malm€o Diet and Cancer study cohort, free from CVD of whom 41 developed CVD and 41 did not. Plasma proteins related to inflammation and thrombo-coagulating processes were analysed. a1-antitrypsin isotype 3 plasma levels were significantly higher while apolipoprotein J plasma levels were lower in participants that developed CVD incidents than those that did not develop acute cardiovascular episode. Of 82 participants, 17 died by CVD causes. There were proteins whose expression in plasma was significantly higher in participants suffering CVD death as compared with those that did not die by CVD. These proteins included: fibrinogen b-chain isotypes 1 and 3, fibrinogen-c-chain isotype 2, vitamin D-binding protein isotypes 1, 2 and 3, a1-antitrypsin isotypes 3 and 6, haptoglobin isotypes 3,4,5 and 5, haemopexin isotypes 1 and 2, and Rho/Rac guanine nucleotide exchange factor 2. Moreover, apolipoprotein J plasma levels were found lower in participants that died by cardiovascular cause. Association between plasma levels of proteins and CVD death was independent of age, gender, conventional risk factors and plasma C-reactive protein levels. Several protein plasma levels and protein isotypes related to inflammation and thrombo-coagulating phenomena were independently associated with the risk of future CVD death., Fondo de Investigaciones de la Seguridad Social, Unión Europea, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

La ablación es una terapia altamente efectiva en el tratamiento de la fibrilación auricular paroxística cuando se compara con la terapia farmacológica. Sin embargo, su elección en pacientes con fibrilación auricular persistente sigue siendo controvertida ya que la evidencia a favor de la ablación es débil, puesto que deriva de ensayos clínicos que comparan estas dos terapias pero que no son aleatorios. Se diseñó este estudio, primer ensayo clínico aleatorizado y controlado para comparar la efectividad del control del ritmo frente a tratamiento antiarrítmico convencional. El objetivo de este estudio fue pues, comparar la eficacia y la seguridad de la ablación frente a la terapia farmacológica antiarrítmica en el mantenimiento del ritmo sinusal en pacientes con fibrilación auricular persistente. Este estudio demuestra que la ablación es superior al tratamiento farmacológico antiarrítmico para lograr el mantenimiento del ritmo sinusal en pacientes con fibrilación auricular persistente a los 12 meses de seguimiento, Background: Catheter ablation (CA) is a highly effective therapy for the treatment of paroxysmal atrial fibrillation (AF) when compared with antiarrhythmic drug therapy (ADT). No randomized studies have compared the two strategies in persistent AF. The present randomized trial aimed to compare the effectiveness of CA vs. ADT in treating persistent AF. Methods and results: Patients with persistent AF were randomly assigned to CA or ADT (excluding patients with long-standing persistent AF). Primary endpoint at 12-month follow-up was defined as any episode of AF or atrial flutter lasting >24 h that occurred after a 3-month blanking period. Secondary endpoints were any atrial tachyarrhythmia lasting >30 s, hospitalization, and electrical cardioversion. In total, 146 patients were included (aged 55 ± 9 years, 77% male). The ADT group received class Ic (43.8%) or class III drugs (56.3%). In an intention-to-treat analysis, 69 of 98 patients (70.4%) in the CA group and 21 of 48 patients (43.7%) in the ADT group were free of the primary endpoint (P = 0.002), implying an absolute risk difference of 26.6% (95% CI 10.0-43.3) in favour of CA. The proportion of patients free of any recurrence (>30 s) was higher in the CA group than in the ADT group (60.2 vs. 29.2%; P < 0.001) and cardioversion was less frequent (34.7 vs. 50%, respectively; P = 0.018). Conclusion: Catheter ablation is superior to medical therapy for the maintenance of sinus rhythm in patients with persistent AF at 12-month follow-up., Medtronic and Biosense Webster, Depto. de Medicina, Fac. de Medicina, TRUE, pub

En el momento de la publicación de este artículo, la revista estaba indexada en ROAD., Las cardiopatías congénitas (CC) son malformaciones del corazón presentes en el feto y/o en el recién nacido, con una tasa de incidencia de 8 por cada 1.000 nacidos vivos, siendo una de las principales causas de mortalidad infantil en España. Los avances científicos producidos en las últimas décadas han logrado disminuirla, permitiendo identificar morbilidades y comorbilidades en el neurodesarrollo de estos infantes. El objeto de este estudio, de carácter cuantitativo, transversal y multicéntrico, es identificar si existen diferencias en las áreas del neurodesarrollo (cognitiva, motora y comunicativa-lingüística) entre los menores, valorados a través de la Escala de Desarrollo Infantil Bayley-III, antes de los 18 meses de edad, a los 18 meses y después de los mismos. Se contó con una muestra de 89 participantes (N=29, < 18 Meses; N=60 ≥18 meses), los cuales presentaban CC, sin anomalías cromosómicas asociadas ni prematuridad, intervenidos mediante cirugía por circulación extracorpórea antes del primer año de vida y valorados en el Hospital U. La Paz de Madrid, en el Hospital 12 de Octubre y en la Fundación Menudos Corazones, en un lapso temporal de tres años (2016-2019). Los resultados hallados evidencian que existen diferencias significativas a nivel cognitivo y motor entre los dos grupos de participantes. Aquellos con una edad inferior a 18 meses alcanzaron media 94.3 y 84.3, respectivamente, frente a los que tenían una edad igual o superior a 18 meses obtuvieron 101.7 y 94.5, respectivamente. Ambos grupos obtienen lentificaciones en el área del lenguaje (media: 86.8) (<18 meses) y (media: 87.4 ≥ 18 meses). Como conclusión, los resultados obtenidos muestran que existen comorbilidades en esta población., Congenital heart disease (CHD) are malformations of the heart present in the fetus and / or in the newborn, with an incidence rate of 8 per 1,000 live births, being one of the main causes of infant mortality in Spain. The scientific advances produced in the last decades have managed to reduce it, allowing us to identify morbidities and comorbidities in the neurodevelopment of these infants. The purpose of this study, quantitative, transversal and multicentric, is to identify if there are differences in the areas of neurodevelopment (cognitive, motor and communicative-linguistic) among minors, assessed through the Bayley-III Child Development Scale, before 18 months of age, at 18 months and after them. There was a sample of 89 participants (N = 29, <18 Months; N = 60 ≥18 months), who presented CC, without associated chromosomal abnormalities or prematurity, operated by surgery for extracorporeal circulation before the first year of life and valued at the U. La Paz Hospital in Madrid, at the Hospital 12 de Octubre and at the Menudos Corazones Foundation, in a three-year period (2016-2019). The results found show that there are significant differences in the cognitive and motor level between the two groups of participants. Those with age less than 18 months reached a mean of 94.3 and 84.3, respectively, compared to those with an age equal to or greater than 18 months obtained a mean of 101.7 and 94.5, respectively. Both groups obtain slowdowns in the area of language 86.8 (<18 months) and 87.4 ≥18 months). In conclusion, the results obtained show that there are comorbidities in this population., Depto. de Estudios Educativos, Fac. de Educación, TRUE, pub

Depto. de Fisiología, Fac. de Medicina, TRUE, pub

Introduction: Radiofrequency (RF) ablation of accessory pathways (APs) is often a time-consuming procedure, mainly because conventional criteria have modest accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was that comparison of paced atrial activation sequences with that obtained during orthodromic AV reentrant tachycardia might be useful for locating the atrial insertion of single APs. Methods and results: The study included 15 patients with a single AP referred for ablation. Analysis of the atrial activation sequence was simplified by measuring the activation time (AT) that elapsed between two atrial reference points placed next to the AV annulus on either side of the area containing the AP. Ablation was guided by conventional criteria. Before each RF delivery, a short pacing train was delivered from the ablation catheter and, after verification of atrial capture, the AT was compared with the AT obtained during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for analysis. The multivariate model with the highest predictive power included a deviation of AT between pacing and tachycardia < or = 5 msec (P < 0.001), a local AV ratio > or = 1 (P = 0.04), and stability of the local electrogram (P = 0.05). The combination of all these criteria predicted a successful application with high sensitivity, specificity, and positive predictive value (92%, 86%, and 71% respectively). To validate the method prospectively, 10 additional consecutive patients underwent an AP ablation procedure guided by these criteria. Conclusion: This technique seems to be highly accurate in selecting the atrial site for RF ablation of single APs., Depto. de Medicina, Fac. de Medicina, TRUE, pub

La ablación con catéter se ha establecido como alternativa o complemento a los fármacos antiarrítmicos en pacientes seleccionados con fibrilación auricular. Aunque el aislamiento de las venas pulmonares es muy eficaz en pacientes con fibrilación auricular paroxística, todavía no somos capaces de identificar el sustrato arritmogénico que origina la fibrilación en un gran número de pacientes, sobre todo aquellos con fibrilación auricular persistente. Este hecho probablemente condicione la ablación de zonas de la anatomía auricular que podrían no ser fundamentales para el inicio y el sostenimiento de la fibrilación auricular. Hasta que conozcamos mejor la fisiopatología de las diferentes etapas de la fibrilación auricular, sería deseable tratar la arritmia precozmente, sin esperar a que evolucione el deterioro anatómico y eléctrico de las aurículas., Depto. de Medicina, Fac. de Medicina, TRUE, pub

This work was supported by the grants from Spanish Ministry of Science and Innovation, PID2019-106581RB-I00 (MM); Leducq Foundation for Cardiovascular Research, TNE-19CVD01 (MM); Fundación La Caixa, HR17_00527 (MM); Instituto de Salud Carlos III and co-financed by the European Development Regional Fund “A Way to Achieve Europe,” PI20/00535 and RETICS RD16/0019/0009 (IL); by contracts FJC-039343-I (AG-C) from the Spanish Ministry of Science and Innovation; and FPU01405265 (VM) and FPU19/02989 (EF) from the Spanish Ministry of Universities. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505)., The substantial clinical burden and disability after stroke injury urges the need to explore therapeutic solutions. Recent compelling evidence supports that neurogenesis persists in the adult mammalian brain and is amenable to regulation in both physiological and pathological situations. Its ability to generate new neurons implies a potential to contribute to recovery after brain injury. However, post-stroke neurogenic response may have different functional consequences. On the one hand, the capacity of newborn neurons to replenish the damaged tissue may be limited. In addition, aberrant forms of neurogenesis have been identified in several insult settings. All these data suggest that adult neurogenesis is at a crossroads between the physiological and the pathological regulation of the neurological function in the injured central nervous system (CNS). Given the complexity of the CNS together with its interaction with the periphery, we ultimately lack in-depth understanding of the key cell types, cell–cell interactions, and molecular pathways involved in the neurogenic response after brain damage and their positive or otherwise deleterious impact. Here we will review the evidence on the stroke-induced neurogenic response and on its potential repercussions on functional outcome. First, we will briefly describe subventricular zone (SVZ) neurogenesis after stroke beside the main evidence supporting its positive role on functional restoration after stroke. Then, we will focus on hippocampal subgranular zone (SGZ) neurogenesis due to the relevance of hippocampus in cognitive functions; we will outline compelling evidence that supports that, after stroke, SGZ neurogenesis may adopt a maladaptive plasticity response further contributing to the development of post-stroke cognitive impairment and dementia. Finally, we will discuss the therapeutic potential of specific steps in the neurogenic cascade that might ameliorate brain malfunctioning and the development of post-stroke, Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Biológicas, TRUE, pub

Background: Findings from animal studies and small series of patients support the greater safety of cryoenergy over radiofrequency in the ablation of arrhythmic substrates near the AV node. Objectives: The purpose of this study was to systematically evaluate the electrophysiologic effects of successive cryoenergy applications to the human AV node in order to better define the safety margin of cryothermal ablation. Methods: In 15 patients referred for AV nodal ablation, 94 cryomapping and 105 cryoablation applications were delivered through a 6-mm-tip cryothermal ablation catheter (Freezor Xtra, CryoCath) at predefined sites of the triangle of Koch. Results: Temporary effects on AV conduction were observed in 18 (19%) cryomapping and 38 (36%) cryoablation applications. Persistent effects were observed in 9 (9%) cryoablation applications. Persistent effects were associated with cryoablation at the superior third of the triangle of Koch (P = .05), nadir tip temperature < or = -79 degrees C (P = .007), and effect onset time < or =15 seconds (P = .03). Temperature and effect onset time remained statistically significant after multivariate adjustment (P = .01 and .02, respectively). Overall, persistent complete AV block was achieved with cryoenergy in only one patient. In two additional patients, AV conduction remained modified. In the remaining patients, persistent complete AV block was achieved with radiofrequency (median one application per patient). Conclusion: The low rate of persistent AV conduction impairment observed with attempts to cryoablate the AV node supports a great safety margin of perinodal cryothermal ablation., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: Results from randomized trials designed to compare cryoenergy with radiofrequency for pulmonary vein (PV) isolation are lacking. Objective: To compare the efficacy of a simplified strategy for PV cryoablation (group C) vs PV isolation with open-irrigated radiofrequency catheters (group R). Methods: Fifty patients with paroxysmal atrial fibrillation (AF) and 4 independent PVs received a Reveal XT implantable cardiac monitor and were randomized to group C or group R. In group C, PV ablation was done with a single Arctic Front balloon (23 or 28 mm) per patient and two 300-second applications per PV. No further applications were delivered to close residual conduction gaps. In group R, bidirectional PV conduction block was pursued with Lasso and Navistar ThermoCool catheters and the CARTO system. The primary end point was the proportion of patients remaining free from AF recurrences ≥2 minutes without taking antiarrhythmic drugs 12 months after ablation. Results: The primary end point was met by 12 (48%) patients in group C and 25 (68%) patients in group R (odds ratio 0.43; P = .05). This difference disappeared after adjustment for acute procedural outcome. In patients for whom all 4 PVs were blocked at the end of the procedure, there was no difference between group C and group R in the primary end point (67% vs 68%; P = .94). Conclusions: The efficacy of the simplified strategy for PV cryoablation tested in this study is inferior to PV isolation using open-irrigated radiofrequency catheters with electrophysiological and electroanatomical guidance. Complete PV conduction block is critical to the success of AF ablation., Depto. de Medicina, Fac. de Medicina, TRUE, pub

We sought to determine if early recurrence of atrial fibrillation (AF) after surgical ablation is a risk factor of late failure. Between February 2004 to May 2009, 106 patients underwent surgical ablation of concomitant permanent AF with radiofrequency. Operations primarily consisted of valve surgery in 85% of patients. Hospital mortality was 2.8% (n = 3). The median follow-up was 37 months (interquartile rank 12-77), and was complete in 99% of patients. Freedom from AF was 82%, 76% and 68% at one, two and three years, respectively. Patients with early recurrence of AF had less prevalence of sinus rhythm in late follow-up (P < 0.001). Multivariate Cox regression analysis showed that AF duration [hazard ratio (HR) 1.014, 95% CI 1.009-1.020, P < 0.001] and early recurrence of AF (HR 3.45, 95% CI 1.50-7.95, P = 0.004) were independent risk factors for failure. In conclusion, in our series, early recurrence of AF after surgical ablation is a strong predictor of late failure., Depto. de Medicina, Fac. de Medicina, TRUE, pub

En el momento de la publicación de este artículo (año 2020), Dialnet métricas informa que la revista presentó un impacto de 0,05 (número de citas 6), situándose en la posición 197 de 240 revistas (Cuartil C4). Esta revista está indexada en Latindex (Catálogo V2.0 2018- ) Pendiente de calificación., Las cardiopatías congénitas son malformaciones del corazón presentes en el recién nacido. Este estudio pretende detectar si las variables biomédicas al nacimiento y al momento de la intervención quirúrgica repercuten en el neurodesarrollo de 80 participantes, sin anomalías cromosómicas asociadas ni prematuridad, valorados a través de Bayley-III. Los resultados evidencian que las variables biomédicas al momento de la intervención quirúrgica (duración de la operación, clampaje, edad de la cirugía y estancia postquirúrgica) son significativas en el neurodesarrollo. Se evidencia una lentificación en los niveles de desarrollo alcanzados en el área del lenguaje desde los 12 meses hasta los 42., Congenital heart diseases are malformations of the heart present in the newborn. This study aims to detect if the biomedical variables at birth and at the time of surgery affect the neurodevelopment of 80 participants, without associated chromosomal abnormalities or prematurity, assessed through Bayley-III. The results show that the biomedical variables at the time of the surgical intervention (duration of the operation, clamping, age of surgery and postsurgical stay) are significant in neurodevelopment. There is evidence of a slowdown in the levels of development reached in the language area from 12 months to 42., Depto. de Estudios Educativos, Fac. de Educación, TRUE, pub

Hay pocos datos sobre la necesidad de cuidados intensivos o la duración adecuada de la estancia hospitalaria de los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST). Con el fin de optimizar los recursos, se intentó determinar la necesidad de ingreso en la unidad de cuidados coronarios (UCC) de los pacientes con IAMCEST que permanecían en clase Killip I tras una tras una intervención coronaria percutánea primaria (ICPP) satisfactoria. Desde agosto de 2006 hasta junio de 2008, analizamos los datos de todos los pacientes ingresados en nuestra UCC que cumplían estos criterios, un total de 278. Se registraron prospectivamente todos los acontecimientos adversos intrahospitalarios y la supervivencia libre de acontecimientos a los 30 y 90 días (muerte por cualquier causa, ictus, nuevo síndrome coronario agudo, rehospitalización por cardiopatía isquémica o por insuficiencia cardiaca). El tratamiento médico se optimizó de acuerdo con las recomendaciones de las guías vigentes. Resultados: Se implantó un stent coronario en el 96% de los pacientes. Ninguno de los pacientes presentó un acontecimiento adverso que no pudiera resolverse en una unidad de cuidados intermedios. La supervivencia a 30 y 90 días fue del 99,6% y el 98,3% respectivamente. La supervivencia sin eventos fue del 97,3% a los 30 días y 94,3% a los 90 días. La mediana de estancia fue de tres días en la UCC y de cinco días en el hospital. Conclusiones: Los pacientes con IAMCEST tratados con ICPP que permanecen en clase I de Killip tras el procedimiento y reciben un tratamiento farmacológico óptimo tienen un pronóstico excelente. Es probable que todos ellos puedan ser ingresados de forma segura en una unidad de cuidados intermedios., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Referencias bibliográficas: • Aguirre, P. et al. (2008): Manual de atención al alumnado con necesidades específicas de apoyo educativo por padecer enfermedades raras y crónicas (en línea). http://www.juntadeandalucia.es/educacion/webportal/ishare-servlet/content/ca17bcc7-9146-455b-a23d-7cdea9ae6546 , acceso 3 de septiembre de 2016. • Alcover, E. et al. (1999): “Seguimiento neurológico y somatométrico de operados cardíacos antes de los 45 días de vida”. Anales Españoles de Pediatría, 51 (1): 60-63. • Armele, M. et al. (2014): “Intervención neuropsicológica en un caso de trastorno del desarrollo generado por una cardiopatía congénita”. Revista Chilena de Neuropsicología, 9 (2): 80-84. • Arretz, C. (2000): “Cirugía de las cardiopatías congénitas en el recién nacido y lactante”. Revista Chilena de Pediatría, 71 (2). • Azcoaga, J. E. (1979): Aprendizaje fisiológico y aprendizaje pedagógico. Buenos Aires: Paidós. • Bayley, N. (2005): Bayley-III, Escalas de desarrollo infantil-III (en línea). http://www.pearsonclinical.es/producto/120/bayley-iii-escalas-bayley-de-desarrollo-infantil-iii , acceso 24 de mayo de 2017. • Dittrich, H. et al. (2003): ”Neurodevelopment at 1 year of age in infants with congenital heart disease”. Heart, 89: 436-441. • DrugFacts (2017): NIH National Institute on Drug abuse. Advancing Addiction Science (en línea). https://www.drugabuse.gov/es/publicaciones/drugfacts/la-comorbilidad-entre-la-adiccion-y-otros-trastornos-mentales , acceso 24 de mayo de 2017. • Esquivel, F. et al. (2013): “Alteraciones electroencefalográficas y del neurodesarrollo en niños portadores de cardiopatías congénitas severas” (estudio preliminar). Gaceta Médica de México, 149: 605-612. • GAT (2000): Libro Blanco de la Atención Temprana. Madrid: Real Patronato sobre Discapacidad. • González, S. (2013): Atención Temprana en niños y niñas con TEA (Trabajo Final de Máster). Instituto Superior de Psicología (ISEP), España. • Gunn, J. et al. (2012): “Perioperative amplitude-integrate, Este estudio se ha realizado para conocer las morbilidades existentes en el desarrollo de los niños que presentan cardiopatías congénitas (CC) intervenidos quirúrgicamente mediante circulación extracorpórea (CEC) y diseñar directrices para su seguimiento e intervención temprana. Se realizó un estudio de corte cuantitativo (N=30), en base a los siguientes criterios de inclusión: edad, tipo de CC e intervención quirúrgica mediante CEC, situados en un rango de edad de 11 a 42 meses. Se evaluó el desarrollo motor, cognitivo y del lenguaje a través de la Escala de Desarrollo Infantil Bayley-III y se tuvieron en cuenta las variables biomédicas. Entre los resultados destaca el hecho de que los participantes en el estudio presentan morbilidades en el área comunicativo-lingüística y motora, existen indicadores biomédicos (edad) en el desarrollo madurativo y necesitan participar en programas de atención temprana (AT) para normalizar su desarrollo. La conclusión es que esta población necesita protocolos interdisciplinares de detección, despistaje e intervención, inexistentes actualmente, y son objeto de recibir AT., This study was carried out in order to report on existing morbidities in the development of children with congenital heart disease (CHD) who underwent Extracorporeal Circulation (ECC) surgery. The purpose of the study is also to design guidelines for the monitoring and early intervention of these conditions. A quantitative study (N=30), based on the following inclusion criteria: age, type of CHD and surgery by ECC, located in an age range of 11 to 42 months, was made. The motor, cognitive and language development was evaluated with help of the Scales of Infant and Toddler Development Bayley-III. The results highlight that the participants present morbidities in the communicativelinguistic and the motor areas. There are biomedical indicators (age) in the maturational development. In order to normalize their development the children would need to participate in early intervention programs (EIP). The conclusion is that this population needs early intervention (EI) and interdisciplinary protocols for detection, screening and intervention that, on this time, are not available., Depto. de Estudios Educativos, Fac. de Educación, TRUE, pub

This retrospective study evaluates the influence of an invasive strategy of urgent coronary revascularization on the in-hospital mortality of patients with acute myocardial infarction (AMI) complicated early by cardiogenic shock. Among 1,981 patients with AMI admitted to our institution from 1994 to 1997, 162 patients (8.2%) developed cardiogenic shock unrelated to mechanical complications. The strategy of management was considered invasive if an urgent coronary angiography was indicated within 24 hours of symptom onset. Every other strategy was considered conservative. Fifty-seven patients who developed the shock late or after a revascularization procedure, or who died on admission, were excluded. The strategy was invasive in 73 patients (70%). Five of them died before angiography could be performed and 65 underwent angioplasty (success rate 72%). By univariate analysis the invasive strategy was associated with a lower mortality than conservative strategy (71% vs 91%, p = 0.03), but this association disappeared after adjustment for baseline characteristics. Older age, nonsmoking, and previous ischemic heart disease were independent predictors of mortality. In conclusion, we have failed to demonstrate that a strategy of urgent coronary revascularization within 24 hours of symptom onset for patients with AMI complicated by cardiogenic shock is independently associated with a lower in-hospital mortality. This strategy was limited by the high mortality within 1 hour of admission in patients with cardiogenic shock, the modest success rate of angioplasty in this setting, and the powerful influence of some adverse baseline characteristics on prognosis., Depto. de Medicina, Fac. de Medicina, TRUE, pub

This work was supported by grants from Instituto de Salud Carlos III and cofinanced by the European Development Regional Fund “A Way to Achieve Europe” (PI17/01601 and RETICS RD16/0019/0009; I.L.), from Regional Madrid Government B2017/BMD-3688 (I.L.); from Spanish Ministry of Economy and Competitiveness SAF2015-68632-R (M.A.M.); from PICATA Project (Campus of international excellence of Moncloa; J.M.P.) and from M+Vision-COFUND Project (J.M.P.) (RTI2018-098682-B-I00 (MCIU/AEI/FEDER, EU) funded by the Spanish Ministry of Science and Innovation (MJLC)., Stroke affects primarily aged and co-morbid people, aspects not properly considered to date. Since angiogenesis/vasculogenesis are key processes for stroke recovery, we purposed to determine how different co-morbidities affect the outcome and angiogenesis/vasculogenesis, using a rodent model of metabolic syndrome, and by dynamic enhanced-contrast imaging (DCE-MRI) to assess its non-invasive potential to determine these processes. Twenty/twenty-two month-old corpulent (JCR:LA-Cp/Cp), a model of metabolic syndrome and lean rats were used. After inducing the experimental ischemia by transient MCAO, angiogenesis was analyzed by histology, vasculogenesis by determination of endothelial progenitor cells in peripheral blood by flow cytometry and evaluating their pro-angiogenic properties in culture and the vascular function by DCE-MRI at 3, 7 and 28 days after tMCAO. Our results show an increased infarct volume, BBB damage and an impaired outcome in corpulent rats compared with their lean counterparts. Corpulent rats also displayed worse post-stroke angiogenesis/vasculogenesis, outcome that translated in an impaired vascular function determined by DCE-MRI. These data confirm that outcome and angiogenesis/vasculogenesis induced by stroke in old rats are negatively affected by the co-morbidities present in the corpulent genotype and also that DCE-MRI might be a technique useful for the non-invasive evaluation of vascular function and angiogenesis processes., Depto. de Bioquímica y Biología Molecular, Fac. de Ciencias Biológicas, TRUE, pub

Background: Current discrimination algorithms do not completely avoid inappropriate tachycardia detection. Objectives: This study analyzes the discrimination capability of the changes of the first postpacing interval (FPPI) after successive bursts of anti-tachycardia pacing (ATP) trains in implantable cardioverter-defibrillator (ICD)-recorded tachycardias. Methods: We included 50 ICD patients in this prospective study. We hypothesized that the FPPI variability (FPPIV) when comparing bursts with different numbers of beats would be shorter in ventricular tachycardias (VTs) compared with supraventricular tachycardias (SVTs). The ATP (5-10 pulses, 91% of tachycardia cycle length) was programmed for tachycardias >240 ms. Results: Anti-tachycardia pacing was delivered during 37 sinus tachycardias (STs) in an exercise test, 96 induced VTs in an electrophysiological study, and 198 spontaneous episodes (144 VTs and 54 SVTs). The FPPI remained stable after all ATP bursts in VT but changed continuously in SVT; when comparing bursts of 5 and 10 pulses, the FPPIV was shorter in VT (34 +/- 65 vs.138 +/- 69, P<.0001, in all T and 12 +/- 20 vs. 138 +/- 69, P<.0001, in T>or=320 ms) than in SVT. In T>or=320 ms an FPPIV

El artículo habla del estudio realizado que investiga los mecanismos que causan la fibrilación ventricular (FV), un ritmo cardíaco peligroso. Se centra en el papel de los canales KATP y su relación con la formación de rotores estables durante la FV. Se realizó un experimento en ocho corazones de cerdo, donde se observó que la apertura de los canales KATP aumentaba la frecuencia cardíaca y la organización de los rotores durante la FV. Estos rotores estables no eran visibles externamente en la fase inicial de la FV. Además, se observó un fenómeno de batido, que sugiere la presencia de rotores en movimiento. Los resultados indican que la FV puede ser impulsada por rotores estables en corazones grandes, con implicaciones importantes para comprender y tratar este trastorno cardíaco., Aims The mechanisms underlying ventricular fibrillation (VF) are still disputed. Recent studies have highlighted the role of KATP-channels. We hypothesized that, under certain conditions, VF can be driven by stable and epicardially detectable rotors in large hearts. To test our hypothesis, we used a swine model of accelerated VF by opening KATP-channels with cromakalim. Methods and results Optical mapping, spectral analysis, and phase singularity tracking were performed in eight perfused swine hearts during VF. Pseudo-bipolar electrograms were computed. KATP-channel opening almost doubled the maximum dominant frequency (14.3 ± 2.2 vs. 26.5 ± 2.8 Hz, P < 0.001) and increased the maximum regularity index (0.82 ± 0.05 vs. 0.94 ± 0.04, P < 0.001), the density of rotors (2.0 ± 1.4 vs. 16.0 ± 7.0 rotors/cm2×s, P < 0.001), and their maximum lifespans (medians: 368 vs. ≥3410 ms, P < 0.001). Persistent rotors (≥1 movie = 3410 ms) were found in all hearts after cromakalim (mostly coinciding with the fastest and highest organized areas), but they were not epicardially visible at baseline VF. A ‘beat phenomenon’ ruled by inter-domain frequency gradients was observed in all hearts after cromakalim. Acceleration of VF did not reveal any significant regional preponderance. Complex fractionated electrograms were not found in areas near persistent rotors. Conclusion Upon KATP-channel opening, VF consisted of rapid and highly organized domains mainly due to stationary rotors, surrounded by poorly organized areas. A ‘beat phenomenon’ due to the quasi-periodic onset of drifting rotors was observed. These findings demonstrate the feasibility of a VF driven by stable rotors in hearts whose size is similar to the human heart. Our model also showed that complex fractionation does not seem to localize stationary rotors., Fundación Mutua Madrileña, Instituto de Salud Carlos III, Unión Europea, Depto. de Medicina, Fac. de Medicina, TRUE, pub

En el momento de la publicación de este artículo, la revista estaba indexada en ROAD., Las cardiopatías congénitas (CC) son consideradas una de las principales causas de mortalidad infantil en España (Tasa de incidencia: 8/1000 nacidos vivos). En las últimas décadas se ha reducido el índice de mortalidad, permitiendo reconocer morbilidades en el neurodesarrollo. Este estudio, de carácter cualitativo, transversal y multicéntrico, trata de identificar si existen o no diferencias en el neurodesarrollo de los menores con CC que están o no escolarizados en centros educativos (CE) o en escuelas infantiles (EI). Cuenta con una muestra total de N=67 con CC, sin anomalías cromosómicas. Los participantes fueron valorados con la Escala de Desarrollo Infantil Bayley-III en la Fundación Menudos Corazones y en el Hospital U. 12 de Octubre de Madrid. La muestra total obtiene puntuaciones que se encuentran dentro del promedio en el desarrollo cognitivo (media: 100.4) y motor (media: 92.2) mientras que alcanzan puntuaciones inferiores en el lenguaje (media: 87.2). Después se analizaron los resultados alcanzados por los menores que asisten a EI (N=24), que están en CE (N=6) y aquellos que no están escolarizados (N=37). Los primeros obtienen media: 105 en el área cognitiva, media: 87.2 en el lenguaje y media: 96.6 en el motor. Los segundos presentan un desarrollo cognitivo (media: 105.8), lenguaje (media:90.5) y motor (media: 97.3) Los terceros tienen puntuaciones inferiores en las tres áreas del desarrollo (media: 96.6; media: 86.6; media: 88.3, respectivamente). En conclusión, los menores con CC que están en CE y/o matriculados en EI obtienen mejores puntuaciones en las áreas del desarrollo que aquellos que no están escolarizados. Es necesario ampliar la muestra de este estudio para generalizar los resultados encontrados., Congenital heart disease (CHD) is considered one of the main causes of infant mortality in Spain (Incidence rate: 8/1000 live births). In the last decades the mortality rate has been reduced, allowing recognizing morbidities in neurodevelopment. This study, of a qualitative, cross-sectional and multicenter nature, seeks to identify whether or not there are differences in the neurodevelopment of children with CHD who are or are not in school (CE) or in nursery schools (IE). It has a total sample of N = 67 with CC, without chromosomal abnormalities. Participants were assessed with the Bayley-III Child Development Scale at the Menudos Corazones Foundation and at the U. October 12 Hospital in Madrid. The total sample obtains scores that are within the average in cognitive development (average: 100.4) and motor (average: 92.2) while reaching lower scores in language (average: 87.2). Afterwards, the results achieved by children who attend EI (N=24), who are in CE (N = 6) and those who are not in school (N = 37) were analyzed. The former get average: 105 in the cognitive area, average: 87.2 in the language and average: 96.6 in the engine. The latter have a cognitive development of average: 05.8, language average: 90.5 and engine average: 97.3. Third parties have lower scores in the three areas of development (average: 96.6; average: 86.6; average: 88.3, respectively). In conclusion, children with CC who are in CE and / or enrolled in EI get better scores in the areas of development than those who are not in school. It is necessary to expand the sample of this study to generalize the results found., Depto. de Estudios Educativos, Fac. de Educación, TRUE, pub

Depto. de Medicina, Fac. de Medicina, FALSE, pub

Introduction and objectives: Little is known about the timing of onset and outcome of conduction abnormalities (CA) following balloon-expandable transcatheter aortic valve implantation. The aim of this study was to examine the timing of CA and determine the impact of balloon aortic valvuloplasty (BAV) on the persistence of these abnormalities. Methods: A total of 347 patients were included. Of these, 75 had a continuous electrocardiogram recording and a 6-lead electrocardiogram at each step of the procedure. Results: In the transcatheter aortic valve implantation population undergoing continuous electrocardiogram monitoring, new-onset left bundle branch block (LBBB) or third-degree atrioventricular block occurred in 48 (64%) and 16 (21.3%) patients, with 51.5% of CA occurring before valve implantation. Left bundle branch block persisted more frequently at hospital discharge (53.8 vs 22.7%; P=.028) and at 1-month follow-up (38.5 vs 13.6%; P=.054) when occurring before valve implantation. Balloon aortic valvuloplasty prior to valve implantation was used in 264 (76.1%) patients, and 78 (22.5%) had persistent LBBB or complete atrioventricular block requiring pacemaker implantation. Persistent LBBB or unresolved atrioventricular block at 1 month occurred more frequently in the BAV group (76.1 vs 47.6%; P=.021), and the use of BAV was associated with a lack of CA resolution (OR, 3.5; 95%CI, 1.17-10.43; P=.021). Conclusions: In patients undergoing a balloon-expandable transcatheter aortic valve implantation, more than half of CA occurred before valve implantation. Early occurrence of CA was associated with a higher rate of persistence at 1-month follow-up. The use of BAV was associated with an increased risk of CA persistence., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background Heart failure with preserved ejection fraction (HFpEF) is a disorder related to patient comorbidities and aging. Whether mitochondrial dysfunction is present during HFpEF decompensation versus the stable phase is largely unknown. The aim of the present study was to identify mitochondrial and cell metabolism blood biomarkers in older patients with acute and stable HFpEF. Methods Peripheral blood biomarkers were investigated in a group of eight to 12 patients aged 80–96 years and diagnosed with HFpEF first when they were in decompensated phase and then at least three months later in stable phase. Their data were compared to two control groups with an equal number of participants and sex proportions. One group was age matched and the other included individuals aged between 22 and 44 years. Results Decompensated patients experienced an increased mitochondrial superoxide production and mitochondrial mass, lower mitochondrial DNA copy number and LDHB expression, and higher lactate level compared to the stable stage. The stable phase was characterized by a sharp reduction in formate level. Multivariate analysis indicated that formate, lactate, and histidine can distinguish both of the HFpEF phases. Many of these parameters, including LDHB, lactate, formate, and mitochondrial mass, followed an age-related pattern, with acute HFpEF at its apex or nadir, suggesting that it represents an exacerbation of an aging-related process. Conclusions We identified distinct blood biomarkers of chronic and decompensated HFpEF phases. The data underlined the relationship between HFpEF and aging. These findings could be used to monitor patients and might be therapeutically targeted., Fundación Hay Esperanza, Instituto de Salud Carlos III, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Objective: To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO). Patients/methods: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100). Results: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786) → C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)(1177), an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177) phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser(1177). On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177). During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets. Conclusions: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177)., Instituto de Salud Carlos III, Unión Europea, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

Fondo Europeo de Desarrollo Regional, Instituto de Salud Carlos III, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: Home blood pressure monitoring has many benefits, even more so, in populations prone to high blood pressure, such as persons with diabetes. Objective: The purpose of this research was to validate the QardioArm mobile device in a sample of individuals with noninsulin-dependent type 2 diabetes in accordance with the guidelines of the second International Protocol of the European Society of Hypertension. Methods: The sample consisted of 33 patients with type 2 diabetes. To evaluate the validity of QardioArm by comparing its data with that obtained with a digital sphygmomanometer (Omron M3 Intellisense), two nurses collected diastolic blood pressure, systolic blood pressure, and heart rate with both devices. Results: The analysis indicated that the test device QardioArm met all the validation requirements using a sample population with type 2 diabetes. Conclusions: This paper reports the first validation of QardioArm in a population of individuals with noninsulin-dependent type 2 diabetes. QardioArm for home monitoring of blood pressure and heart rate met the requirements of the second International Protocol of the European Society of Hypertension., Depto. de Enfermería, Fac. de Enfermería, Fisioterapia y Podología, TRUE, pub

The purpose of this study was to compare the effect of dual antiplatelet therapy [clopidogrel + aspirin (ASA)] with respect to ASA on the protein expression of platelets from controlled type-2 diabetic patients with stable coronary ischemia. Patients had been taking ASA (100 mg day) and they were randomized to receive (n = 29) or not (n = 28) 75 mg day clopidogrel for 12 ± 2 weeks in a blind form. Protein expression was analyzed by two-dimensional electrophoresis and mass spectrometry. The protein expression of a limited number of proteins such as actin-binding protein isotypes 2 and 5, lactate dehydrogenase, serotransferrin isotype 4, protein disulfide isomerase-A3 isotype 1, fibrinogen beta chain isotype 5, Ras-related protein Rab-7b isotypes 1 and 6, and immunoglobulin heavy chain was changed after dual antiplatelet therapy. Plasma level of platelet factor 4 (PF4), an in vivo marker of platelet activity, was not different between both groups. These changes suggest lower platelet reactivity after dual antiplatelet therapy in the studied patients. However, the variation in platelet proteome was lower than it would be initially expected, taking into account the apparent clinical beneficial effects of dual antiplatelet therapy. PF4 plasma level was not further decreased in the platelets treated for a longer time than 9-12 months with ASA + clopidogrel, as compared with ASA alone., Fondo de Investigacion de la Seguridad Social, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub

About 30% of patients treated with cardiac resynchronization therapy (CRT) do not respond to treatment. The aim of this study was to identify clinical predictors of lack of improvement in patients receiving CRT. From 197 consecutive patients scheduled to receive CRT, 143 fulfilled the inclusion criteria. Mean age was 68 +/- 7 years and 79% were men. Heart failure was due to ischemic heart disease in 49 patients (34%). Mean QRS duration was 165 +/- 26 ms, and left ventricular ejection fraction was 27 +/- 7%. Nonresponder patients were defined as those who died of heart failure, underwent heart transplantation, or did not increase the distance walked in 6 minutes >10%. At 6-month follow-up, there were 28 nonresponders (20%). Among nonresponders, 2 patients received a heart transplantation and 9 patients died of heart failure. In logistic regression analysis, independent predictors of lack of response to CRT were ischemic heart disease (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.2 to 7; p = 0.023), severe mitral regurgitation (OR 3.5, 95% CI 1.3 to 9; p = 0.014), and left ventricular end-diastolic diameter > or =75 mm (OR 3.1, 95% CI 1.1 to 8; p = 0.026). Patients with these 3 predictors had a probability response of 27%., Depto. de Medicina, Fac. de Medicina, TRUE, pub

Depto. de Fisiología, Fac. de Medicina, TRUE, pub

This study was supported by the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI16/188, PI19/855), the European Regional Development Fund, and the European Commission through H2020-EU.1.1, European Research Council grant ERC-2016-StG 715322-EndoMitTalk, and Gobierno de España SAF2016-80305P. This work was partially supported by Comunidad de Madrid (S2017/BMD 3867 RENIM-CM) and cofinanced by the European Structural and Investment Fund. M.M. is supported by the Miguel Servet Program (CP 19/014, Fundación de Investigación del Hospital 12 de Octubre). J.O., E.G., and R.R-D. are supported by Juan de la Cierva (FJCI2017-33855, IJC2018-036850-I, and IJCI2017-31399, respectively). Support was also provided by Ministerio de Ciencia e Innovación grants (RTI2018-099246-B-I00 to J.M.R. and PI18/00543 to J.F.N.) and Comunidad de Madrid and Fondo Social Europeo funds (AORTASANA-CM; B2017/BMD-3676 to A.M.B., A.F., and J.M.R.). J.M.R. was also funded by Fundacion La Caixa (HR18-00068) and the Marfan Foundation (USA). J.M.R. and J.L.M.V. were also funded by Centro de Investigación Biomedica en Red Enfermedades Cardiovasculares of Ministerio de Ciencia e Innovación (CB16/11/00264). J.F.N. was funded by Ministerio de Economía y Competitividad (PI18/00543) and Centro de Investigación Biomedica en Red Enfermedades Cardiovasculares (CB16/11/00264), and was cofunded by Fondo Europeo de Desarrollo Regional., Background: Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the FBN1 (fibrillin-1) gene encoding a large glycoprotein in the extracellular matrix called fibrillin-1. The major complication of this connective disorder is the risk to develop thoracic aortic aneurysm. To date, no effective pharmacologic therapies have been identified for the management of thoracic aortic disease and the only options capable of preventing aneurysm rupture are endovascular repair or open surgery. Here, we have studied the role of mitochondrial dysfunction in the progression of thoracic aortic aneurysm and mitochondrial boosting strategies as a potential treatment to managing aortic aneurysms. Methods: Combining transcriptomics and metabolic analysis of aortas from an MFS mouse model (Fbn1c1039g/+) and MFS patients, we have identified mitochondrial dysfunction alongside with mtDNA depletion as a new hallmark of aortic aneurysm disease in MFS. To demonstrate the importance of mitochondrial decline in the development of aneurysms, we generated a conditional mouse model with mitochondrial dysfunction specifically in vascular smooth muscle cells (VSMC) by conditional depleting Tfam (mitochondrial transcription factor A; Myh11-CreERT2Tfamflox/flox mice). We used a mouse model of MFS to test for drugs that can revert aortic disease by enhancing Tfam levels and mitochondrial respiration. Results: The main canonical pathways highlighted in the transcriptomic analysis in aortas from Fbn1c1039g/+ mice were those related to metabolic function, such as mitochondrial dysfunction. Mitochondrial complexes, whose transcription depends on Tfam and mitochondrial DNA content, were reduced in aortas from young Fbn1c1039g/+ mice. In vitro experiments in Fbn1-silenced VSMCs presented increased lactate production and decreased oxygen consumption. Similar results were found in MFS patients. VSMCs seeded in matrices produced by Fbn1-deficient VSMCs undergo m, Depto. de Genética, Fisiología y Microbiología, Fac. de Ciencias Biológicas, TRUE, pub

Stroke patients have a high risk of vascular recurrence. Biomarkers related to vascular recurrence, however, remain to be identified. The aim of the study was to identify, through proteomic analysis, plasma biomarkers associated with vascular recurrence within one year after the first ischemic stroke. This is a substudy (n = 134) of a large prospective multicenter study of post-stroke patients with an ischemic stroke. Plasma samples were obtained at inclusion. Among the identified proteins, only plasma levels of desmoplakin I were associated with protection against a new vascular event (Odds ratio: 0.64; 95% CI: 0.46-0.89; p = 0.009) after adjustment for hypercholesterolemia, statins and previous atherothrombotic stroke subtype. A greater number of patients without vascular recurrence had been treated with statins within three months of the recent ischemic stroke. Only patients who had been taking statins for 3 months after the ischemic stroke and did not suffer vascular recurrence over a follow-up year, have higher levels of desmoplakin I at the time of inclusion (Odds ratio 0.49; 95% CI: 0.28-0.86; p = 0.013). Increased desmoplakin I levels, determined within 1-3 months of the first ischemic stroke, could be a biomarker for statin responsiveness against a new vascular event in post-ischemic stroke patients taking statins early (1-3 months) after the ischemic stroke., Brystol-Myers Squibb, Fondo de Investigaciones de la Seguridad Social, Depto. de Salud Pública y Materno - Infantil, Fac. de Medicina, TRUE, pub