Resultados a largo plazo del trasplante intracoronario de células mononucleares de médula ósea autólogas en pacientes con cardiopatía dilatada de diversa etiología / Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy

Background: Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. Aim: To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. Patients and Methods: Prospective, open-label, controlled clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone marrow mononuclear cell intracoronary transplantation, receiving a mean dose of 8.19 ± 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and cancer incidence rate, changes in functional capacity, quality of life questionnaires and echocardiographic measures from baseline, were assessed at long-term follow-up (37.7 ± 9.7 months) in patients receiving or not the cells. Results: No significant differences were observed in mortality, cardiovascular readmissions or cancer incidence rate amongst groups. An improvement in functional class and quality of life questionnaires in the transplanted group was observed (p < 0.01). The treated group showed a non-significant increase in left ventricular ejection fraction at long-term follow-up (from 26.75 ± 4.85% to 34.90 ± 8.57%, p = 0.059 compared to baseline). There were no changes in left ventricular volumes. We observed no improvement of these variables in the control group. Conclusions: Intracoronary transplantation of autologous bone marrow mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of diverse etiologies. This therapy was associated to persistent improvements in functional class and quality of life. There was also a non-significant long-term improvement of left ventricular function.

Estado actual de la terapia con células madre en el tratamiento de las cardiopatías / Stem cells for the treatment of cardiovascular diseases. An update

Available medical therapy is unable to completely prevent or revert the pathological cardiac remodeling secondary to ischemia or other injuries, which is responsible for the development of heart failure. Regenerative medicine through stem cells had an explosive development in the cardiovascular area during the past decade. Stem cells possess the capacity to regenerate, repair or substitute damaged tissue, allowing the reestablishment of its function. Stem cells can also modulate apoptosis, angiogenesis, fibrosis and inflammation, favoring the endogenous regenerative process initiated by the damaged tissue. These capacities have been corroborated in several animal models of cardiovascular diseases with positive results. In humans, therapies with bone marrow mononuclear stem cells, mesenchymal stem cells and cardiac stem cells are safe. Most randomized clinical trials in patients with myocardial infarction or cardiomyopathies of different etiologies have reported benefits on ventricular function, quality of life and even over mortality of treated patients. This article reviews the state of art of stem cell therapy in cardiovascular diseases, focusing on the most common cellular types used in patients with acute myocardial infarction and chronic cardiomyopathies of different etiologies.

El trasplante intracoronario de células mononucleares de médula ósea se asocia a mejoría la función ventricular izquierda, en pacientes con cardiopatía dilatada de diferente etiología: Proyecto INNOVA Chile N°205-4350 / Autologous bone marrow cell transplantation improves ejection fraction in patients with dilated cardiomyopathy of diverse etiologies: Proyecto innova chile n° 205-4350

Introducción: Estudios recientes indican que el trasplante intracoronario de células mononucleares de médula ósea (BMCs) autólogas, mejoran la fracción de eyección (FEVI) y otros marcadores clínicos en pacientes con insuficiencia cardíaca (IC). Objetivo: Evaluar la seguridad y eficacia de la administración intracoronaria de BMCs autólogas, en pacientes con insuficiencia cardíaca (IC) en fase dilatada, de diferente etiología y en óptimas condiciones de tratamiento médico. Método: De 23 pacientes consecutivos que cumplieron con los criterios de inclusión, 12 fueron asignados a trasplante intracoronario de BMCs autólogas, recibiendo una dosis media de 8.19+/-4.43 x 10(6) células CD34+ (Grupo trasplantado). Los pacientes restantes sólo recibieron terapia estándar (Grupo control). Todos los pacientes fueron evaluados mediante Electrocardiograma, Ecocardiografía, Holter ECG, RMN Cardíaca, Test de esfuerzo, Potenciales Ventriculares Tardíos, Variabilidad de Frecuencia Cardíaca y evaluación clínica a los 0, 3, 6 y 12 meses. La capacidad funcional (CF) fue evaluada clínicamente y por cuestionarios de calidad de vida. Elanálisis estadístico fue realizado mediante Test Anova, y test de Bonferroni. Resultados: El grupo trasplantado presentó un aumento significativo de la FEVI a los 6 meses (26.75+/-4.85 vs 37.82+/-6.97 por ciento, p=0.001) mejoría que se mantuvo a los 12 meses (26.75+/-4.85 vs 37.27+/-7.51 por ciento, p=0.002). Hubo una mejora significativa de la CF en el grupo trasplantado a los 6 y 12 meses (p<0.001). No hubo cambios significativos en los volúmenes de ventrículo izquierdo, así como en las restantes variables estudiadas. En el grupo control no observamos cambios de estas variables. No hubo complicaciones en relación al trasplante de BMCs. Conclusión: En pacientes con IC severa y baja FEVI, el trasplante intracoronario de células BMCs au-tólogas, se asoció a una mejoría significativa de la FEVI y la CF, a los 6 y 12 meses. Adicionalmente, no observamos ...

Background: Recent studies indicate that intra-coronary delivery of autologous bone marrow mono-nuclear cells (BMCs) improves the ejection fraction (LVEF) and other clinical markers in patients with heart failure (HF). Aim: To evaluate the safety and efficacy of intraco-ronary delivery of autologous BMCs in patients with HF in dilated phase under optimal medical treatment. Method: Of 23 consecutive patients who met the inclusion criteria, 12 were assigned to autologous BMCs intracoronary transplantation, receiving a mean dose of 8.19+/-4.43 x 106 CD34+ cells (BMCs group). The remaining patients received only standard therapy (control group). All patients were evaluated by Electrocardiogram, Echocardiography, Holter Monitoring, Cardiac Magnetic Resonance Imaging, Stress Testing, Ventricular Late potetials, Heart Rate Variability, and regular clinical examination at baseline and at follow-up (3, 6 and 12 months). Repeated measures ANOVA and Bonferroni testing were used for statistic analysis. Results: The BMCs group presented a significant increase in EF at sixth months (26.75+/-4.85 vs. 37.82+/-6.97 per cent, p=0.001) and 12 months post-transplant (26.75+/-4.85 vs. 37.27+/-7.51 per cent, p=0.002). There was a significant improvement in functional (NYHA) in the transplanted group at 6 and 12 months (p<0.001). There were no significant changes concerning left ventricular volumes, heart rate variability and exercise stress testing. We observed no improvement of these variables in the control group. There were no complications related to the BMCs transplant. Conclusions: Intracoronary infusion of auto-logous BMCs, in addition to standard therapy, was associated with significant improvement of left ventricular function at 12 months in patients with HF. We observed no complications relative to the procedure.

Resultados Chilenos del registro internacional de factores de riesgo y tratamiento de angina inestable e infarto al miocardio sin supradesnivel del segmento ST: ACCORD (ACute CORonary syndrome Descriptive study) / Chilean results of the international registry of risk factors and treatment of unstable angina and non ST elevation myocardial infarction: ACCORD (ACute CORonary syndrome Descriptive study)

Background: Guidelines for the management of unstable angina (UA) and non ST elevation myocardial infarction (NSTEMI) have been issued, however cu-rrent practices are unknown in Chile. Aitn: To evalúate in a prospective cohort of NSTEMI patients the current practices, treatments and risk factors. Material and Methods: Oneyear prospective International non interventional registry, conducted in Chile between January 2005 and November 2006. Results: Two hundred thirty three Chilean NSTEMI patients were enrolled. Mortality was 5.5 percent at the end ofthe follow-up. Mean age was 61.6 years, and 30.6 percent were female. Most of the patients had at least one risk factor (98 percent): hypertension (84 percent), previous myocardial infarction (33 percent), dyslipidemia (54 percent), diabetes (33 percent), current smoking (30 percent). Main procedures duringthe hospitalization were coronary angiogram (67 percent), angioplasty (33 percent; 88 percent with stent) and coronary bypass surgery (7 percent). Duringprocedures, 31 percent of patients received clopidogrel, and 4.2 percent glycoprotein Ilb/IIIa antagonists. Medical management was selected for 60 percent of patients. In comparison to men, women received less interventional procedures despite havingmore risk factors. Treatments prescribed at discharge were aspirin (97 percent), clopidogrel (49 percent), beta blockers (78 percent), diuretics (21 percent), lipid lowering agents (78 percent), oral hypoglycemic agents (13 percent) and insulin (9 percent). At the end ofthe 1-year follow-up, treatments were aspirin (84 percent), beta blockers (72 percent), diuretics (19 percent), and dual antiplatelet therapy with clopidogrel (16 percent). Conclusions: A high prevalence of múltiple risk factors for cardiovascular disease in Chilean patients with NSTEMI was observed. More aggressive primary and secondary preventive measures are urgently needed. Use of therapies proposed in the guidelines is high, but dual antiplatelet therapy is less than 50 percent at discharge and decreases during the one year-follow-up.

Implicancias de la glicemia de ingreso en la mortalidad intrahospitalaria y alejada según el método de reperfusión en pacientes con infarto agudo del miocardio y supradesnivel del segmento ST / Admission hyperglycemia and mortality of ST segment elevation myocardial infarction

Background: Hyperglycemia at admission has been associated to an adverse prognosis in patients with ST-segment elevation acute myocardial infarction (STE-MI). However, its impact over the results of reperfusion therapies in patients with STEMI is still a matter of controversy. Aim: To determine the impact of admission hyperglycemia on hospital and long term mortality, according to the method of reper-fusion utilized in patients with STEMI. Material and Methods: Prospective registry of 1,634 consecutive patients aged 60 ± 12 years (77 percent male), from 3 participating hospitals in the Chilean Registry of Myocardial Infarction (GEMI). We evaluated demographic, clinical and laboratory variables, reperfusion method used, hospital and long term mortality. The impact of hyperglycemia on hospital and long term mortality was evaluated by a logistic regression analysis and Cox risk, respectively, adjusted by Thrombolysis in Myocardial Infarction (TIMI) risk score. Results: Twenty four percent of patients were diabetics and in 45 percent, the infarct was located on the anterior wall. The mean TIMI risk score was 3.2 ± 2.4. Hyperglycemia at entry was associated to a greater hospital and long term mortality, independently of the reperfusion strategy utilized. Primary angioplasty was associated to a greater benefit, compared to thrombolysis among hyperglycemic patients with an odds ratio: 2.9, 95 percent confi dence intervals: 1.0-8.0 and a hazard ratio of 2.9, 95 percent confi dence intervals: 1.44-5.88, independently of a previous history of diabetes mellitus and TIMI risk score. Conclusions: In patients with STEMI, admission hyperglycemia is associated with a worse prognosis which was significantly improved with primary angioplasty compared to thrombolysis, independently of the admission TIMI risk score.

Evaluación a largo plazo del impacto funcional y estructural de la arteria radial post acceso en intervencionismo coronario / Long term evaluation of functional and structural changes of the radial artery used as access for cardiac interventional procedures

Resumen: Antecedentes: El acceso radial es una alternativa aceptable y segura para procedimientos endovasculares. Sin embargo no existe una clara evaluación de la integridad de la arteria radial (AR) post procedimiento. Objetivo: Evaluar el impacto funcional y estructural a largo plazo de la punción y colocación del introductor vascular en arteria radial (AR) post intervencionismo coronario. Método: Se estudian 33 pacientes con cardiopatía coronaria a quienes se realizó coronadografía y/o angioplastía vía radial. A los 6-10 meses de seguimiento se analizó las características ecográficas funcionales y estructurales de la AR comparándola con la AR contralateral. Resultados: Con el seguimiento se observan 3 AR ocluidas (9 por ciento). No se encontró un aumento significativo del grosor de la pared a nivel distal (zona de punción), 0,36 +/- 0,22 vs 0,28 +/- 0,08mm; el diámetro fue similar a nivel distal 2,6 +/- 0,7mm vs 2,8 +/- 0,35mm (ns) y proximal 2,8 +/- 0,35 vs 2,5 +/- 0,7mm. No hay diferencia significativa en la velocidad peak sistólica (VPS), en la AR puncionada vs la control 54 +/- 16 vs 50 +/- 14 cm/seg ni en los índices de resistencia 0,83 +/- 0,1 vs 0,87 +/-0,1. Conclusiones: La utilización de la vía radial para intervencionismo coronario ocasiona en un bajo porcentaje la oclusión esta arteria. En las arterias que permanecen permeables no se encontró a largo plazo un impacto sobre las características estructurales ni funcionales.

Background: the radial artery is a common and safe access site for endovascular procedures. There has been no adequate evaluation of the radial artery integrity following the procedure. Aim: to evaluate the long term functional and structural status of the radial artery use for cardiac interventional procedures Methods: 33 patients with coronary artery disease had coronary angiography and/or PTCA using the radial artery approach. After 6-10 months the functional and structural status of the artery was evaluated by comparison to the contra lateral artery Results: Three (9 percent) arteries were occluded. No thickening of the arterial wall distal to the puncture site was observed. Diameters were 2.6 +/- 0.7 vs 2.8 +/- 0.35mm (punctured vs control) distally and 2.8 +/- 0.35 vs 2.5 +/- 0.7mm proximally. Respective peak systolic flow velocities were 54 +/- 16 vs 50 +/- 14 cm/sec (NS) and resistance indexes were 0.83+/-0.1 compared to 0.67+/-0.1 (NS) Conclusion: A low percent of radial arterial occlusion is observed following use of the radial artery following cardiovascular interventions. Patent arteries showed no structural or functional limitations at long term evaluation.

Intervencionismo en oclusiones crónicas: evaluación de la efectividad cruce de distintas guías y balones según complejidad / Percutaneous coronary interventions in chronic coronary occlusions: effectiveness of different guides and balloons according to complexity of total coronary artery occlusion

Antecedentes: El intervencionismo en las oclusiones totales crónicas (OTC) requiere técnicas complejas y el éxito es poco predecible. Es útil identificar la efectividad de las guías de cruce y del balón para el intervencionismo en distintos niveles de complejidad de OTC. Objetivos: Evaluar la efectividad de cruce de distintas guías y balones en el tratamiento de OTC. Métodos: Se revisa en forma retrospectiva la efectividad de distintos tipos de guías y balones de cruce utilizados en intervencionismo de OTC efectuados entre agosto de 2007 y agosto de 2009. Se define "efectividad" como la capacidad de avanzar y cruzar la oclusión crónica con la guía y el balón, ambas necesarias para efectuar la angioplastia de la OTC. Se agrupan los resultados según el nivel de complejidad de la OTC de acuerdo a score propio, distinguiendo entre OTC simples, complejas y de alta complejidad. Resultado: En el período estudiado se revisan 90 OTC. Se utilizan 148 guías (1,6 guía/proc.) y se utilizan 92 balones en 76 procedimiento que logran paso efectivo de guía. (1,2 bal/proc). Se realiza una tabla con la tasa de efectividad de distintas guías y balones de cruce. Destaca la utilidad de guía PT2 en lesiones simples y complejas, como la utilidad de la guía Miracle 6 en OTC de alta complejidad. Conclusiones: En OTC se obtiene un éxito de 67 por ciento en nuestro medio, con mayor efectividad de la guía PT2 en lesiones simples y complejas y de Miracle 6 en lesiones de alta complejidad. En cuanto a balones se obtiene mayor efectividad en los tipo Maverick, Mercury y Voyaguer de 1,5 mm en lesiones simples y complejas, como del Balón Maverick de 1,5 mm en lesiones de alta complejidad. Es de gran utilidad un registro de la efectividad de balones y guías en el tratamiento de OTC, lo que permite al intervencionista una adecuada elección del material con el consecuente ahorro de tiempo y mayor efectividad del procedimiento.

Background.: PCI in chronic coronary occlusions requires complex techniques and is associated to less predictable results. It is important to evaluate the effectiveness of different guides and balloons in PCI for total coronary occlusion (TCO). Aim: To evaluate the effectiveness of different guides and balloons in the treatment of TCO. Methods: A retrospective review of the effectiveness of different guides and balloons in the treatment of TCO performed from 2007 to 2009 was carried out Effectiveness was defined as the ability to traverse the occlusion with the guide and the balloon. The analysis was performed according to groups defined by the complexity of the TCO as assessed by a locally developed score. Occlusions were classified as simple, complex or highly complex. Results: 90 procedures were analyzed 148 guides were utilized (mean of 1.6 per procedure) and 92 balloons were used in 76 cases were the guide successfully crossed the occlusion. The PT2 guide was effective for simple and complex lesions, whereas de Miracle 6 guide was effective in the treatment of highly complex lesions. Regarding balloons, the Maverick, Mercury and Voyageur 1.5 mm were satisfactory in simple and complex lesions, while the Maverick 1.5mm was more effective in highly complex lesions Conclusion: TCO was successfully treated by PCI in 67 percent of cases. PT2 guides and all types of balloons were effective for treatment of simple and complex lesions. In contrast, the Miracle 6 guide and the Maverick 1.5 balloon were more effective in highly complex lesions. These findings may be useful to help de proper selection of angioplasty materials when treating.

Impacto de la trombolisis y de la angioplastia primaria en pacientes con infarto agudo del miocardio tratados en centros hospitalarios terciarios / Mortality of patients with ST-elevation acute myocardial infarction treated with primary angioplasty or thrombolysis

Background: Primary angioplasty is the most effective treatment of ST-segment elevation acute myocardial infarction (STEMI). However, its worldwide implementation is difficult to obtain. Therefore thrombolysis continues to be the treatment most commonly used. Aim: To evaluate inhospital and long term mortality of patients with STEMI treated with thrombolysis or angioplasty, in three hospitals participating in the Chilean National Registry of Acute MI (GEMIgroup). Material and tnethods: Registry of 1,634 consecutive patients with STEMI admited between 2002 and 2006. Risk was stratified using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score. Hospital and log term mortalities were adjusted using logistic and Cox regression models. Results: Fifty nine percent of patients (967 patients aged 60±12 years, 77 percent males) were subjected to reperfusion therapies, 28 percent with primary angioplasty and 72 percent with thrombolysis. Hospital mortality rates among patients treated with thrombolysis and angioplasty were 10.9 percent and 5.6 percent (p =0.01), respectively The figures for long term mortality were 20.4 percent and 9.7 percent, respectively (p <0.01). Multivariate analysis confirmed the lower mortality among subjects treated with angioplasty, with an odds ratio (OR) in favor of angioplasty of 8.5 (95 percent confidence intervals (CI) 3-35) for in hospital mortality and of 4.7 (95 percent CI 2.6-8.3) for long term mortality. The higher benefits of angioplasty were observed in males, in the elderly and in patients with a TIMI score over >3. Conclusions: Hospital and long term mortality of patients with STEMI was lower among those treated with primary angioplasty. This treatment is most beneficial among males, in the elderly and in patients with a TIMI score >3.

Proteína ligadora de ácidos grasos de miocito: marcador precoz de infarto agudo al miocardio / Myoccityc fatty acid-binding protein: early markers in acute myocardial infarction

La cardiopatía coronaria es la primera causa de muerte en Chile y el infarto agudo del miocardio una de las patologías con garantías explícitas recientemente implementadas, exigiendo un diagnóstico precoz (30 minutos desde el momento de la consulta). Las troponinas e isoformas mb de la creatinfosfoquinasa son marcadores tardíos de daño miocárdico. La proteína ligadora de ácidos grasos de miocito (h-FABP), proteína citosólica del citoesqueleto miocárdico, es un marcador precoz de necrosis miocárdica detectándose ya a los 30 minutos de la injuria. Objetivo: Determinar la presencia temprana de h-FABP en síndrome coronario agudo (SCA) con supradesnivel del segmento ST (SDST) y su correlación tardía con diagnóstico infarto agudo del miocardio (IM). Materiales y métodos: Se reclutó a pacientes con SCA SDST con <6 horas de inicio de sus síntomas entre el 1/8/04 al 6/9/05 en el Servicio de Urgencias del Hospital del Salvador. Con registro de antecedentes personales, clínicos, electrocardiográficos, troponinas y/o CPK mb. Se correlacionó h-FABP (test rápido inmunoensayo de anticuerpos monoclonales, cualitativo (Cardiodetect®)) con diagnóstico confirmado de IM. Se analizaron sensibilidad, especificidad, valor predictivo positivo (VPP), negativo (VPN), cociente probabilidad positivo y negativo con programa estadístico PRIMER 4,06®. Resultados: 45 pacientes con SCA SDST. El 65,9 por ciento de género masculino. Rango de edades entre 38 y 82 con promedio de 63,4±16,4 años. Se registraron como factores de riesgo: tabaquismo 68,1 por ciento, hipertensión arterial 46,7 por ciento, dislipidemia 29,3 por ciento, cardiopatía coronaria 13,8 por ciento. Características electrocardiográficas: pared anterior 43,5 por ciento, inferior 36,7 por ciento, bloqueo completo de rama izquierda 19,8 por ciento. Se obtuvo una sensibilidad de 85,7 por ciento, especificidad: 60 por ciento, valor predictivo positivo: 80,2 por ciento y valor predictivo negativo: 54,7 por ciento. Cociente de probabilidad positiva 2,41 y cociente de probabilidad negativa 0,24 Taylor. Chi cuadrado por Mantel Haenszel p=0,0007. Conclusiones: La h-FABP es un marcador precoz, de fácil implementación y rápido resultado en el infarto agudo del miocardio, potencialmente útil para el diagnóstico en IM dada su alta sensibilidad y cociente de probabilidad.

Eficacia de F18_fluorodeoxiglucosa SPECT para evaluar infarto reciente y viabilidad miocárdica / Efficacy of F18_fluorodeoxiglucose SPECT for recent infarction evaluation and myocardial viability

El mejor examen disponible para evaluar viabilidad miocárdica es el Fluor18-fluordeoxiglucosa (F18FDG) que mide metabolismo celular y utilización de glucosa como sustrato. Su asociación a marcadores de flujo miocárdico permiten conocer la existencia y extensión de tejido con función potencialmente recuperable. El objetivo de este trabajo fue evaluar el rendimiento del F18FDG SPECT en pacientes con infarto reciente de miocardio. Material y Método: Se estudiaron preliminarmente 23 pacientes (7M,16H), edad promedio 63 ñ 13 años (rango:40-85), con evolución promedio de 10 días postinfarto (rango:5-24). En 14 casos, el infarto fue anterior y en 9 casos inferior. Se realizó F18FDG en cámara ADAC doble cabezal con colimadores de 511 Kev, con dosis promedio de 211 MBq (rango: 52-444) , con adquisición de las imágenes a los 45 min postinyección. Contemporáneamente, se efectuó Tl201 SPECT reposo redistribución con dosis de 148 MBq y adquisición de imágenes a los 10 min y 3 hrs. Se realizó análisis visual de ambos estudios en forma independiente dividiendo el miocardio en 17 segmentos (total de segmentos: 391). Resultados: Tanto en el SPECT con Tl201 como en el con F18 FDG hubo 21/23 (91 por ciento) de casos con segmentos alterados, en que hubo concordancia de 83 por ciento. En el Tl201 reposo redistribución, se encontraron 32 por ciento de segmentos alterados y en el estudio conjunto Tl201 reposo F18 FDG, se observó un 34 por ciento de segmentos alterados del total de los analizados. En dichos segmentos, el Tl201 reposo redistribución mostró 65 por ciento de segmentos viables y el Tl201 F18 FDG 77 por ciento de segmentos con viabilidad. Conclusión: 1) Tanto el Tl201 como el estudio con F18 FDG tienen buena concordancia, tanto por pacientes como por segmentos, en el infarto reciente de miocardio. 2) El SPECT Tl201 asociado a F18 FDG detecta un mayor número de segmentos viables que el examen de Tl201 reposo- redistribución aislado