Cuantificación de la extrasistolía supraventricular y ventricular en el Holter de 24 horas: significación pronóstica en estudios actuales

En la actualidad existen diferencias en la interpretación y cuantificación de los extrasístoles supraventriculares y ventriculares en el Holter de ritmo cardíaco y no existe siempre una misma definición e interpretación de lo que se denomina como "escaso", "ocasional", "frecuente" o "muy frecuente". El objetivo del presente trabajo ha sido revisar las evidencias actuales y sus fundamentos en relación a la cuantificación o carga de la extrasistolía supraventricular y ventricular en un Holter de ritmo cardíaco, lo que debiera contribuir a una mayor precisión y mejor interpretación de la información cuantitativa en la práctica clínica diaria con este examen. Se revisa en la literatura el concepto de carga de extrasístoles supraventriculares y ventriculares y su relación con eventos clínicos: fibrilación auricular y accidente cerebrovascular en el caso de la extrasistolía supraventricular y mortalidad post infarto y deterioro de la función ventricular en el caso de la extrasistolía ventricular. De esta manera se cuantifica en base a la evidencia la extrasistolía supraventricular y ventricular.

Considerable differences exist in the quantification and clinical significance of both supraventricular and ventricular extrasystoles found in Holter recordings. Usually extrasystoles were classified as rare, occasional, frequent and very frequent. Current publications were analyzed regarding the frequency and clinical significance or these arrhythmias, especially in in relation to prior myocardial infarction, ventricular dysfunction, atrial fibrillation and cerebro vascular events. Tables showing limits to define the severity of supraventricular and ventricular extrasystoles are included.

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

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

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

Cardiotoxicidad inducida por tratamientos oncológicos: fundamentos para la implementación de equipos de Cardio-Oncología / Cardiotoxicity of anticancer therapies: towards the implementation of cardio-oncology units

Recently, we have witnessed major improvements in cancer treatment. Early diagnosis and development of new therapies have reduced cancer-related mortality. However, these new therapies, along with greater patient survival, are associated with an increase in untoward effects, particularly in the cardiovascular system. Although cardiotoxicity induced by oncologic treatments affects predominantly the myocardium, it can also involve other structures of the cardiovascular system, becoming one of the main causes of morbidity and mortality in those who survive cancer. The main objective of cardio-oncology is to achieve the maximum benefits of oncologic treatments while minimizing their deleterious cardiovascular effects. It harbors the stratification of patients at risk of cardiotoxicity, the implementation of diagnostic tools (imaging techniques and biomarkers) for early diagnosis, preventive strategies and early treatment options for the complications. Herein, we discuss the basic knowledge for the implementation of cardio-oncology units and their role in the management of cancer patients, the diagnostic tools available to detect cardiotoxicity and the present therapeutic options.

Ácido úrico: una molécula con acciones paradójicas en la insuficiencia cardiaca / The role of uric acid in heart failure

Complications and mortality of heart failure are high, despite the availability of several forms of treatment. Uric acid, the end product of purine metabolism would actively participate in the pathophysiology of heart failure. However, there is no consensus about its action in cardiovascular disease. Serum uric acid would have a protective antioxidant activity. This action could help to reduce or counteract the processes that cause or appear as a result of heart failure. However, these protective properties would vanish in the intracellular environment or in highly hydrophobic areas such as atherosclerotic plaques and adipose tissue. This review discusses the paradoxical action of uric acid in the pathophysiology of heart failure.

Cambios en el pronóstico a largo plazo de la hipertensión arterial pulmonar / Changes long term prognosis of 17 patients with pulmonary artery hypertension

Background: Pulmonary artery hypertension (PAH) is a progressive disease with high mortality. Major advances had been made in the treatment of this condition during the last decade. Aim: To characterize the clinical evolution and mortality of a cohort of Chilean patients. Material and Methods: Seventeen patients with PAH diagnosed in the last 10 years in two Chilean hospitals were enrolled. Measurements at diagnosis included hemodynamic variables and 6-minute walk test. The patients were followed clinically for 3 years and the observed mortality was compared with that predicted by the prognostic equation proposed by the historic registry of the National Institutes of Health (NIH). Results: The mean age of patients was 45 years and 80 percent had an idiopathic PAH. The mean median pulmonary artery pressure was 57 ± 15 mmHg, the cardiac index was 2.4 ± 0.7 l/min/m² and the right atrial pressure was 12 ± 8 mmHg. The 6-minute walk distance was 348 ± 98 m. All patients received anticoagulants. Eighty two percent received ambrisentan, 12 percent received bosentan, 29 percent received iloprost and 24 percent sildenafil. At the end of follow-up only 3 patients had died, with an observed survival rate of88, 82 and 82 percent at 1, 2 and 3 years, respectively. In contrast, the survival calculated according to the predictive formula of the NIH was 67, 56 and 45 percent, respectively. Among surviving patients, an improvement in exercise capacity was observed after one year (p < 0.05). Conclusions: The observed survival rate was significantly better than that estimated according to historical data. Furthermore, therapy was associated with an improvement in functional capacity after one year. This prognostic improvement is consistent with data of other contemporary registries published after the NIH Registry.

Determinaciones de niveles de creatina y lípidos mediante espectroscopia por resonancia magnética en miocardio de pacientes con insuficiencia cardiaca no isquémica / Myocardial lipids and creatine measured by magnetic resonance spectroscopy among patients with heart failure

Background: Heart failure (HF) is characterized, among other features, by the development of alterations in myocardial energy metabolism, involving a decrease in glucose utilization and increased free fatty acid uptake by cardiomyocytes, associated with decreased deposits of high-energy phosphates (creatine phosphate/ creatine transporter). Magnetic resonance (MR) imaging allows a direct and noninvasive assessment of myocardial metabolites. Aim: To measure myocardial creatine and lipids by MR spectroscopy among patients with HF. Material and Methods: Cardiac MR spectroscopy (1.5 Tesla) with Hydrogen antenna and single voxel acquisition was performed in fve patients with non-ischemic heart failure, aged 58 ± 9.7 years, (60 percent males) and 5 healthy volunteers matched for age and sex. We analyzed the signals of creatine (Cr), lipids (L) and water (W) in the interventricular septum, establishing the water/lipid (W/L) and water/creatine (W/Cr) index to normalize the values obtained. Results: Among patients, left ventricular ejection fraction was 32 ± 6.9 percent, 60 percent were in functional capacity II, 60 percent had hypertension and one was diabetic. Spectroscopic curves showed a depletion of total Cr, evidenced by the W/ Cr index, among patients with heart failure, when compared with healthy controls (1.46 ± 1.21 and 5.96 ± 2.25 respectively, p < 0,05). Differences in myocardial lipid content, measured as the W/L index, were not significant (5.06 ± 2.66 and 1.80 ± 1.62 respectively, p = 0.08). Conclusions: Among patients with heart failure of non-ischemic etiology, there is a depletion of creatine levels measured by MR spectroscopy.

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.

Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca / Heart energy metabolism and its role in the treatment of heart failure

It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

Niveles aumentados de estrés oxidativo se asocian a disfunción endotelial periférica y respuesta vascular pulmonar disminuida frente a vasodilatadores en pacientes con hipertensión pulmonar / Increased oxidative stress are associated with peripheral endothelial dysfunction and diminished vascular response to vasodilators in pulmonary hypertensive patients

Introducción: La Hipertensión arterial pulmonar (HP) se caracteriza por remodelado vascular y disfunción endotelial. Evidencia experimental muestra que el estrés oxidativo juega un rol importante en la patogénesis de la HP. El rol del estrés oxidativo, su relación con la función endotelial periférica y con la respuesta vascular pulmonar a vasodilatadores en pacientes con HP no está aclarada. Objetivo: evaluar parámetros de estrés oxidativo y función endotelial periférica en pacientes con HP y estudiar su relación con la respuesta vascular pulmonar frente a vasodilatadores. Métodos: estudio transversal. Se incluyeron 14 pacientes con HP y 14 controles pareados por edad y sexo. En todos los sujetos se midieron: niveles plasmáticos de malondialdehido (MDA), superóxido dismutasa ligada a endotelio (eSOD) y xantino oxidasa (eXO). Vasodilatación dependiente de endotelio mediada por flujo en arteria braquial fue usada como marcador de función endotelial (FDD). Función ventricular derecha y reactividad del lecho vascular pulmonar frente a iloprost inhalado fueron evaluadas ecocardiográficamente en los pacientes con HP Resultados: Los pacientes con HP presentaron FDD disminuida versus los controles (2,8 +/- 0,6 vs 10,7 por ciento +/- 0,6, p< 0,01). Niveles de MDA y eXO aumentados (0,61 +/- 0,17 vs 0,34 +/- 0,15uM, p<0,01 y 0,039 +/- 0,005 vs 0,034 +/- 0,004 U/mL1, p=0,02 respectivamente) y actividad de eSOD disminuida (235,55 +/- 23 vs 461,41 +/- 33 ABC, p<0,01). Iloprost mejora significativamente el gasto cardíaco derecho y disminuye la resistencia vascular pulmonar en los pacientes con HP y este cambio se correlaciona con la actividad de eSOD (Rho: 0,61, p<0,01) y FDD (Rho: 0,63, p=0,01). Conclusiones: Pacientes con HP presentan parámetros de estrés oxidativo elevados y disfunción endotelial periférica La respuesta hemodinámica frente al uso de Iloprost se correlaciona con estos parámetros sugiriendo un rol en la HP cuyo valor clínico deberá ser evaluado.

Background: Pulmonary Arterial Hypertension (PAH) is characterized by endothelial dysfunction and vascular remodeling. Several lines of experimental evidence indicate that oxidative stress plays an important role in the pathogenesis of PAH. The role of oxidative stress and its relation with peripheral endothelial function and pulmonary vascular response to vasodilators remains unknown. Aim: To evaluate whether systemic oxidative stress and endothelial dysfunction markers are associated with the response of the pulmonary vascular bed to inhaled vasodilators in PAH patients. Methods: Cross-sectional study Fourteen patients with PAH and 14 age and gender-matched controls were included. Systemic oxidative stress was assessed through plasma malondialdehyde (MDA), xanthine oxidase (eXO) levels and endothelial-bound superoxide dismutase (eSOD) activity Brachial artery endothelial-de-pendent flow-mediated vasodilation (FDD) was used to evaluate endothelial function. Right ventricular function and pulmonary vascular bed reactivity to inhaled vasodilators was determined with echocardiography in PAH patients. Results: Compared to controls, PAH patients showed impaired FDD (2.8 +/- 0.6 vs 10.7 percent +/- 0.6, p< 0.01), increased MDA and eXO levels (0.61 +/- 0.17 vs 0.34 +/- 0.15uM, p<0.01 and 0.039 +/- 0.005 vs 0.034 +/- 0.004 U/ mL1, p=0.02 , respectively) and decreased eSOD activity 235.55 +/- 23 vs 461.41 +/- 33 AUC, p<0.01). Iloprost significantly improved right cardiac output (RCO) and decreased pulmonary vascular resistance. The amount of change in RCO after iloprost inhalation correlated significantly with baseline eSOD activity and FDD (Rho: 0.61, p<0.01 and Rho: 0.63, p=0.01 respectively). Conclusions: PAH patients show increased oxidative stress and endothelial dysfunction markers. Response to inhaled iloprost is closely related with baseline endothelial function and oxidative stress parameters, suggesting an important role of these elements that re...

Miocardiopatía dilatada secundaria a enfermedad celíaca: Caso clínico / Dilated cardiomyopathy in celiac disease: Report of one case

There is an increased incidence of celiac disease in patients with idiopathic dilated cardiomyopathy. We report a 4 7 year-old female presenting with heart failure secondary to dilated cardiomyopathy of unknown etiology. During the five months following the first hospitalization the patient had multiple hospital admissions due to decompensate heart failure. Due to a history of intermittent diarrhea and weight loss, a celiac disease was suspected. Antiendomysial antibodies were positive and there was a villous atrophy in duodenal mucosa. A gluten free diet was started with a concomitant recovery of her functional capacity. After one month of gluten free diet a new echocardiogram showed a normal left ventricle and systolic function.

El tratamiento con atorvastatina reduce la actividad de xantina-oxidasa unida al endotelio en pacientes con insuficiencia cardíaca crónica: ¿un posible nuevo efecto pleiotrópico? / Treatment with atorvastatin reduces the activity of xanthine oxydase bound to endothelium in patients with chronic heart failure

El aumento en la actividad de la xantina-oxidasa unida al endotelio (XOec) puedeparticipar como un importante mediador de la disfunción endotelial en la insuficiencia cardíaca crónica (IC). Las estatinas son capaces de reducir el estrés oxidativo y restaurar la disfunción endotelial a través de mecanismos independientes de la reducción del colesterol. Sin embargo, el efecto de estos fármacos en la actividad de XOec es completamente desconocido. Nosotros estudiamos la hipótesis que atorvastatina durante 8 semanas reduce la actividad de XOec de manera independiente de los cambios en el colesterol. Metodología: Un total de 25 pacientes con IC (Fracción de eyección < 40 por ciento y Clase funcional NYHA II-III) recibieron placebo por 4 semanas, seguido por 8 semanas de atorvastatina 20 mg por día. Muestras desangre fueron recolectadas basalmente, 4 semanas y 12 semanas. La actividad de XOec y los niveles de ácido úrico fueron medidos por espectrofotometría.Resultados: El tratamiento con atorvastatina, pero no el placebo, redujo la actividad de ecXO (p<0.01), los niveles de ácido úrico (p<0.05), colesterol total (p<0.01), LDL-colesterol (p<0.01) y triglicéridos (p<0.05) sin cambios en los niveles de HDL-colesterol y creatinina. Además, no se encontraron correlaciones estadísticas entre la fracción de cambio de XOec y las fracciones de cambio de parámetros lipídicos. Conclusión: El efecto beneficioso a corto plazo de la atorvastatina en relación a la mejoría de la función endotelial demostrado en estudios previos, estaría asociado a una disminución en la actividad de XOec de una manera independiente a los cambios en el colesterol, lo que sugiere la presencia de un nuevo efecto pleiotrópico de las estatinas.

An increased activity of endothelium bound xanthine oxydase (XOeb) may play an important role as a mediator of endothelial dysfunction in chronic heart failure (CHF). Statins reduce oxydative stress and improve endothelial dysfunction through mechanisms unrelated to cholesterol lowering. However, the effect of statins on XOeb activity is unknown. We hypothesized that atorvastatin administered for 6 weeks would reduce XOeb independently of changes in serum cholesterol levels. Methods: 25 patients with CHF (NYHA class II or III with ejection fraction <40 percent received placebo for 4 weeks followed by atorvastatin, 20mg per day, for 8 weeks. Blood samples were obtained before statin administration and 4 and 12 weeks later. Spectrophotometry was used to determine XOeb and uric aced levels. Results: Atorvastatin, but not placebo, reduced XOeb activity (p<0.01), and uric acid (p<0.05), total cholesterol (p<0.01), LDL-cholesterol (p<0.01) and triglyceride levels (p<0.05). No changes were observed inHDL and creatinine levels. There was no correlation between XOeb changes and changes in the other lipid parameters. Conclusion: The known improvement in endothelial dysfuncion related to statin use previously reported is associated to a decrease in XOec activity independently of changes in cholesterol levels, suggesting a new pleiotropic effect of statins.

Cardiotrofina-1 circulante puede diferenciar la hipertrofia ventricular fisiológica del atleta de la hipertrofia patológica del paciente hipertenso / Corculating cardiotrophyn-1 may help differenciate left ventricular hypertrophy seen in athletes from pathologic left ventricular hypertrophy associated to hypertension

Introducción: Cardiotrofina-1 (CT-1), una citoquina perteneciente a la superfamilia de la interleukina-6, se encuentra elevada en pacientes con hipertensión arterial (HTA) e hipertrofia ventricular izquierda (HVI). Sus niveles se correlacionan con el tamaño auricular izquierdo y con las presiones de llenado del ventrículo izquierdo. Los niveles de CT-1 en atletas con HVI fisiológica no han sido investigados. Métodos: Estudio transversal. Se incluyeron pacientes con HTA esencial con y sin evidencia ecográfica de cardiopatía hipertensiva (CH)(HVI y relación E/E´>10), recientemente diagnosticada y sin tratamiento. Un grupo de atletas normotensos con diagnóstico ecográfico de HVI y un grupo control de sujetos normotensos pareados por edad y sexo. En todos los sujetos se midieron los niveles plasmáticos de CT-1 (ELISA). Se definió HVI utilizando el índice de masa ventricular izquierda con ecocardiograma usando la fórmula de Devereux (hombres ≥ 115 gramos/m2, mujer ≥ 95 gramos/m2). Las presiones de llenado del VI se estimaron con la relación E/E’ (doppler tisular en el anillo mitral medial). Resultados: Se incluyeron 10 pacientes por grupo. Los atletas con HVI presentaron una relación E/E´ < a 10, y ésta no fue distinta al grupo control y a la de los hipertensos sin HVI y fue significativamente menor respecto de los hipertensos con CH (6,5 +/- 1 versus 12,9 +/- 1,1, p < 0,01). Respecto de los niveles de CT-1 los atletas con HVI presentaban niveles menores que los pacientes hipertensos con evidencia de CH (6,6 fmol/ml +/- 0,4 versus 18,2 fmol/ml +/- 5,6, p < 0,001) y niveles similares al grupo control y de hipertensos sin evidencia de CH. Conclusión: En atletas con HVI los niveles de CT-1 son similares a los de sujetos normotensos y a los de pacientes hipertensos sin HVI, y significativamente menores respecto a los de pacientes hipertensos con niveles similares de HVI y disfunción diastólica.

Background: Cardiotrophyn-1 (CT-1), is a cytokine which is increased in patients with hypertension (HT) and left ventricular hypertrophy (LVH). This increase occurs in proportion to left atrial size and left ventricular filling pressures. CT-I levels in athletes with LVH have not been investigated Methods:Crossectional study. We evaluated; a) hypertensive patients with LVH and E/E> 10 by echocardiography, recently diagnosed and receiving no medications; b) normotensive athletes with LVH as shown by echocardiography, and c) normotensive subjects, paired by age and sex. Plasma levels of CT-i (ELISA) were measured in all. L VH was defined as left ventricular mass index> 115 G/m2 (males) or> 95 G/m2 (females). Results: EIE’ was lower in athletes than hypertensive patients with LVH (6.5 +/- I vs 12.9 +/- II, p<0.01). EIE’ in both control subjects and patients with HTA but no LVH did not differ from EIE’ in athletes. CT-I was lower in athletes than patients with HTA and LVH (6.6 +/- 0.4 vs 18.2 +/- 5.6 fmol/ml, respectively, p<0.00l). CT-I levels in control subjects and hypertensive patients without LVH did not differ from that found in athletes. Conclusion: CT-I levels are similar in athletes compared to normal subjects and patients with HTA and no LVH. Hypertensive patients with similar grades of LVH and left ventricular diastolic dysfunction had significantly greater leves of CT-I. Thus, CT-I levels could help differentiate pathological HVI from physiologic LVH in athletes

Utilidad del cierre del foramen oval permeable en pacientes con AVE criptogénico / Closure of patent foramen ovale in patients with cryptogenic stroke

Antecedentes: El foramen oval permeable (FOP) es un hallazgo frecuente en pacientes con accidente vascular encefálico criptogénico (AVEC), y se discute la utilidad de su cierre percutáneo (CP). Objetivo: Evaluar el riesgo de recurrencia de eventos neurológicos en pacientes con AVEC y FOP, y compararlos entre aquellos tratados médicamente y los sometidos a CP. Métodos: Entre los 106 pacientes admitidos por AVEC y FOP, en el período 2003 a 2006, determinamos la aparición de nuevos eventos neurológicos isquémicos (NEN), y estudiamos sus factores determinantes y comparamos los que se sometieron a CP versus lo que continuaron con tratamiento médico, según criterio del tratante. Se consignaron las características clínicas y de la antomía del FOP en el ecocardiograma Los NEN se confirmaron por examen neurológico y/o neuro-imágenes. Para el análisis de los datos se utilizó chi-cuadrado y regresión logística.Resultados: Entre los 106 pacientes evaluados, 87 siguieron tratamiento médico y 19 CP. Los pacientes sometidos a CP presentaban mayor asociación de FOP con aneurisma del septum interauricular (ASI) (57,9% versus 35,6%, p=0,05). El seguimiento fue de 27 +/-13 meses. En este período se demostró un 12,6% de nuevo evento neurológico entre los tratados médicamente, mientras que ninguno lo presentó entre los sometidos al CP (NS). El único predictor independiente para NEN fue el ASI asociado con FOP; OR: 8,45 (1,56-60,46). Conclusiones: De acuerdo a nuestros resultados, los pacientes con AVEC y FOP tienen alto riesgo de recurrencia cuando el FOP se asocia a ASI y aparentemente se benefician con CP.

Background: Patent Foramen Ovale (PFO) is a frequent finding in patients with cryptogenic stroke (CS). Theeffect of closing the PFO in this setting is debated. Aim: to evaluate de risk of stroke recurrence in patients with CS and PFO; to compare this risk in patients followed under medical treatment with those undergoing percutaneous closure of PFO. Methods: From 2003 to 2006, 106 patients were admitted with a CS and the presence of PFO was documented by echocardiography. New ischemic strokes and risk factors were compared between those who weresubmitted to percutaneous closure of PFO and those treated in a conventional way. The decision to close thePFO was taken by the physician in charge. Clinical findings and echocardiographic characteristics of thePFO were recorded. New ischemic events were diagnosed by neurologic assessment and/or imaging techniques. Data was analyzed by chi square testing and logistic regression. Results: 87 patients were followed under medical treatment and 19 had closure of the PFO. The latter group had a greater incidence of atrial septal aneurysm (57.9% vs. 35.6%, p=0.05). The mean follow up was 27 +/- 13 months.New ischemic stroke occurred in 12.6% in the medically treated group while none was observed in the PFO closure group (NS). The sole independent predictor of new stroke was the presence of atrial septal aneurysm (OR: 8.45, 95% C.I. 1.56 - 60.46) Conclusion: Patients with CS and PFO are at considerable risk of developing new strokes, especially those with concomitant atrial septal aneurysm. Closure of PFO was apparently useful to prevent this risk.

Interacción entre los polimorfismos del receptor ß1 y ß2 adrenérgico como predictor de riesgo de insuficiencia cardiaca crónica / Interactions between ß1 and ß2 adrenergic receptor polymorphisms as risk factors for chronic heart failure

Background: ß adrenergic receptors (AR) are highly polymorphic and important regulators of cardiovascular homeostasis. Among these, ß1 and ß2 AR regulate cardiac contractility and frequency and are important pharmacological targets. Aim: To evaluate genotype and gene-gene interaction between ß1-AR Arg389Gly and ß2-AR ArglSGly GlnZ7Gly and Thrl 64Ile polymorphisms, as risk factors for HF. Material and methods: Eighty chronic HF patients and eighty-eight controls matched by age and sex were genotyped for ß1 -AR Arg389Gly ß2-AR ArgWGly, GlnZ7Glu and Thr164Ile polymorphisms. Results: The presence of ß2-AR Glu afiele was a risk predictor for HF (odds ratio (OR) =2.81; 95 percent confidence intervals (CI) =1.49-5.31). Interactions that increased the risk for HF were found in patients carrying at least one of the ß2-AR Glu and ß2-AR Gly allele (OR =3.81; 95 percent CI =1.50-0.70) and ß2-AR Glu and ß1 -AR Gly allele combination (OR =5.51; 95 percent CI =2.19-13.86). Furthermore, the frequency of ß2-AR Glu allele was higher among patients with a history ofacute myocardial infarction (with infarction: 0.534, without: 0.313, p =0.01). Conclusions: ß2-AR Glu allele could be a risk predictor for HF. This risk could be enhanced by the additional presence of ß2-AR GlyW or ß1-AR Arg389 alleles. The frequency of ß2-AR Gln27 Glu allele was higher among patients with a history of myocardial infarction.

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.

Inflamación y disfunción endotelial en pacientes con insuficiencia cardiaca crónica / Inflammation and endothelial dysfunction in patients with chronic heart failure

Background: In chronic heart failure (CHF), endothelial dysfunction (ED) is a consequence of an imbalance of vascular tone regulating substances. The relationship between ED and inflammation has not been fully investigated. Aim: To assess the association between inflammation and ED in CHF. Material and methods: Forty two patients aged 56±14 years (80 percent male) with a CHF in functional capacity II-III (New York Heart Association) and an ejection fraction (FE) <40 percent were consecutively studied. Patients were classified according to the presence or absence of ED, evaluated by reactive vasodilation measured by ultrasound, after brachial artery compression. Circulating levels of highly sensitive C reactive protein (usCRP), tumor necrosis factor a (TNFá) and interleukin-6 (IL-6) were determined by ELISA. A group of 15 healthy subjects of similar age, were studied as controls. Results: Sixty seven percent of patients had ED. Compared to controls, patients with CHF had higher usCRP (0.58±0.4 and 4.9±7.1 mg/dl respectively, p <0.01) and IL-6 (1.38±0.06 and 3.1±1.7 mg/dl respectively, p <0.01). Compared to patients without ED, patients with CHF and ED had higher levéis of usCRP (3.0±0.4 and 6.0±5.7 mg/dl respectively, p <0.01) and TNFá (0.31±0.26 and 1.0±1.1 pg/ml, p =0.02). No differences in IL-6 were found between CHF groups. Conclusions: In CHF patients, the presence of ED was associated with increased levéis of inflammatory markers.

Superóxido dismutasa ligada al endotelio es un sensible marcador de estrés oxidativo y disfunción endotelial en la insuficiencia cardíaca / Endothelial linked superoxide dismutase is a sensitive marker of oxidative stress and endothelial dysfunction in patients with congestive heart failure

Introducción: En pacientes con insuficiencia cardíaca (IC) existe activación neurohumoral que contribuye a la progresión clínica de la enfermedad y se ha asociado a aumento del estrés oxidativo (EO) y deterioro de la capacidad funcional. Pacientes con IC avanzada tienen niveles aumentados de malodihaldehido, un marcador de EO, pero niveles normales de enzimas antioxidantes. En la pared vascular, la enzima superóxido dismutasa ligada a endotelio (SODec) representa un importante sistema enzimático antioxidante que contribuye a la inactivación de especies reactivas del oxígeno (ROS) y a la modulación del tono vascular. Objetivo: Estudiar el rol de SODec como marcador de EO en IC y su correlación con la función endotelial. Métodos: Estudiamos 20 pacientes con IC moderada (Clase II-III) con fracción de eyección de ventrículo izquierdo (FEVI) < 40 por ciento. Se determinaron los niveles plasmáticos de MDA por sustancias reactivas del ácido tiobarbitúrico y los sistemas de defensa antioxidantes eritrocitarios SOD y catalasa (CAT) por espectofotometría. La enzima ecSOD se liberó de la superficie endotelial mediante la administración de heparina en bolo (5000 U) en la arteria braquial determinando su actividad en sangre venosa. La función endotelial se determinó mediante ecografía de arteria braquial para determinar la vasodilatación dependiente de endotelio. Se utilizó un grupo control de personas sanas pareadas por edad y sexo. Los resultados se expresan como promedio ± DES y en el análisis estadístico se utilizó t-Student y correlación lineal de Pearson. Resultados: Edad promedio de 59 ± 16 años, 17 hombres (85 por ciento). Nueve con etiología isquémica (45 por ciento). La FEVI fue de 33 ± 5 por ciento, el test de caminata de 6 minutos de 412 ± 90 m. Los niveles plasmáticos de MDA y de SOD y CAT eritrocitarios fueronsimilares en pacientes con IC y en grupo control. En los pacientes con IC encontramos una disminución significativa de la actividad de SODec (p< 0.001)...

Niveles de péptido natriurético cerebral y su relación con capacidad funcional y hemodinamia pulmonar en pacientes con hipertensión pulmonar primaria: Correlation with functional capacity and hemodynamic parameters / Brain natriuretic peptide in primary pulmonary ypertension

Background: Primary pulmonary hipertension (PPH) is a progressive disease leading to right heart failure and death. Right heart catherization and maximal or submaximal tests are employed to assess the course of the disease. A neurohormonal parameter such as pro-brain natriuretic peptide (BNP) would be helpful in the assessment of these patients. Aim: To study the correlation of BNP with functional status and non-invasive hemodynamic determinations in patients with PPH. Material and methods: Twelve patients (mean age: 48 years; 58% female) were evaluated with 6 minutes walk distance test (6-min WT), plasma BNP, systolic pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and cardiac output (CO) determined by echocardiogram. Plasma BNP levels were compared with normal subjects. Results: BNP levels were increased in PPH patients (1270±547 vs 48±8 pg/ml, p-value <0.01). Mean PAPs was 82±27 mmHg and the mean distance walked in 6 minutes was 407±113 meters. BNP levels were positively correlated with PVR (r=0.58, p-value=0.006) and negatively correlated with 6-min WT (r=-0.83, p-value <0.001). No correlation was found between BNP levels, PAPs and CO. Conclusions: In PPH patients, BNP levels are increased and correlate with functional class and PVR. Follow-up studies are needed to evaluate the role of BNP as a marker of progression and therapeutic response in PPH patients.

Efectos del Carvedilol sobre la sincronía ventricular en pacientes con insuficiencia cardíaca congestiva / Effects of Carvedilol on ventricular synchrony in patients with congestive heart failure

Introducción: Carvedilol es un bloqueador adrenérgico que mejora el remodelamiento ventricular izquierdo y reduce la morbi-mortalidad de los pacientes con insuficiencia cardíaca congestiva (ICC). Esto podría estar relacionado con una corrección de la sincronía ventricular. Objetivo: Evaluar el efecto de Carvedilol sobre la sincronía en la contracción ventricular en pacientes con ICC. Métodos: Se estudiaron 30 pacientes con ICC estable, capacidad funcional NYHA (CF) II-III, fracción de eyección (FE) < 40 por ciento, los cuales estaban tratados en forma habitual. Se excluyeron pacientes usuarios de betabloqueadores o de marcapaso. Se realizó ventriculografía radioisotópica de equilibrio, al inicio y posterior a la terapia con Carvedilol por 6 meses, para evaluar la función sistólica y la sincronía ventricular. La sincronía interventricular fue calculada mediante la diferencia de promedio de fase de ambos ventrículos y la intraventricular usando la desviación estándar del análisis de fase. Resultados: La edad fue 55 ± 13 años, 71 por ciento hombres, 35 por ciento de etiología isquémica y 29 por ciento con bloqueo completo de rama izquierda (BCRI). Posterior a la terapia con Carvedilol (dosis promedio de 22 mg, rango de 6.25 – 50 mg/día) hubo una mejoría en la CF y en la distancia recorrida en 6 min (499 ± 18 m a 534 ± 17 m ). La FE mejoró de 24 ± 8.3 por ciento a 31 ± 11. 3 por ciento (p<0.001). En los pacientes con peor sincronía, bajo el percentil 50, mejoró la sincronía intraventricular (113 ± ms vs. 94 ± 38 ms, p=0.02) e interventricular (62.8 ± 7 ms vs. 39.4 ± 9 ms, p=0.02). Los pacientes con etiología no isquémica tuvieron una mejoría en la sincronía intraventricular (103.8 ± 7 ms vs 78.3 ± 12 ms, p=0.04) e interventricular (68.1 ± 9 ms vs. 35.3 ± 12 ms, p=0.02). En aquellos sin BCRI mejoró la sincronía intraventricular (112.1 ± 8 ms vs. 88.5 ± 11.2 ms, p=0.01). No hubo cambios significativos en pacientes con causa isquémica o con BCRI. Conclusiones: En pacientes con IC y disfunción ventricular izquierda, Carvedilol mejora la sincronía intra e interventricular. Estos efectos podrían estar relacionados a una acción favorable sobre el remodelamiento cardíaco.

Polimorfismos de los receptores -β adrenérgicos y su relación con el riesgo de insuficiencia cardiaca, etiología y prevalencia de infarto al miocardio / Polymorphysm of beta-adrenergic receptors and risk of heart failure, etiology and prevalence of myocardial infarction

Introducción: Los polimorfismos de los receptores ß-adrenérgicos (AR) influencian el grado de actividad del receptor. Los ßAR tienen un rol importante en la regulación de la contractilidad y podrían tener implicancias en el riesgo de desarrollar insuficiencia cardiaca (IC), como en su pronóstico y respuesta terapéutica. Objetivo: Evaluar los genotipos e interacciones genéticas entre los polimorfismos del ß1 y ßAR como predictores de riesgo de desarrollar IC, su relación con la etiología de la IC y prevalencia de infarto. Métodos: Se genotipificaron 80 pacientes con IC y 88 sujetos sanos por edad y sexo. Los pacientes con IC tenían FE<35 por ciento y CF II-IV de la NYHA. Los polimorfismos se determinaron amplificando por la Reacción de Polimerización en Cadena (PCR) los genes de los ßAR y analiz¨¢ndolos con enzimas de restricción (PCR-RFLP). Los datos se analizaron mediante los tests estadísticos c2, Fisher, regresión loguística y razón de disparidad. Los datos se ajustaron por edad y sexo. Las interacciones entre los polimorfismos ß1AR Arg389 →Gly, ß2Ar Gln27 →Glu y ß2AR Thr 164 →lle se evaluaron en función del riesgo a desarrollar ICC. Resultados: Las frecuencias de los genotipos ß2AR Gln27→Glu y 1 AR Arg389→Gly fueron diferentes en los sujetos con IC comparados con los controles. La presencia del ß2AR Glu27Glu pero no de la variante 1 AR Gly389Gly fue predictor de ICC (OR ajustado=2,81; Cl=1,49 a 5,31 para el 2AR Glu27Glu; p=0,001 y OR ajustado=0,58; Cl=0,13 a 2,53; p=0,466 para b1AR Gly389Gly). Se encontró una interacción entre los polimorfismos ß1AR Arg389Arg y los polimorfismos del ß2AR Arg16Arg, Gln27Gln, y Thr164Thr. Estas interacciones se asociaron a una reducción en el riesgo de IC (OR=0,25, Cl=0,09 a 0,69; p=0,009; OR=0,18, Cl=0,07 a 0,46, p<0,001 y OR=0,48, Cl=0,25 a 0,91, p=0,026, respectivamente). Además, en los pacientes con IC, la frecuencia del polimorfismo 2AR Glu27Glu se asoció con una mayor incidencia de infarto al miocardio (con infarto: 0,534, sin = 0,313, p=0,01). Conclusiones: La variante Glu27Glu del ß2AR fue un predictor de IC, los polimorfismos del ß2AR Arg16Arg, Gln27Gln, y Thr164Thr y 1AR Arg389Arg se asociaron a una disminución del riesgo de ICC. El genotipo y frecuencia del alelo ß2AR Gln27 ----- Glu se relacionó a la etiología de la ICC y con la prevalencia de infarto al miocardio. Estos hallazgos pueden ser relevantes en la predicción de riesgo de ICC, su pronóstico y respuesta terapéutica.