[Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years]. / Endocarditis infecciosa: características clínicas, complicaciones y mortalidad en 506 pacientes y factores pronósticos de sobrevida a 10 años (1998-2008). Estudio cooperativo nacional en endocarditis infecciosa en Chile (ECNEI-2).

BACKGROUND: Rates of morbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. AIM: To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. MATERIAL AND METHODS: Observational prospective national cohort study of 506 consecutive patients included between June 1,1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. RESULTS: The main findings were the presence of Rheumatic valve disease in 22.1 % of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylococcus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% of patients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28.33%), failure of medical treatment and no surgical intervention (OR 48.8; CI 6.67-349.9). Five and 10 years survival rates were 75.6 and 48.6%, respectively. The significant prognostic factors for long term mortality, determined by multivariate analysis were the presence of diabetes, Staphylococcus aureus infection, sepsis, heart failure, renal failure and lack of surgical treatment during the IE episode. CONCLUSIONS: The microbiologic diagnosis of IE must be urgently improved in Chile. Mortality rates are still high (26.1%) partly because of a high incidence of negative blood cultures and the need for more surgical valve interventions during in-hospital period. Long term prognostic factors for mortality should be identified early to improve outcome.

[Tako-Tsubo syndrome: report of one case]. / Síndrome de Tako-Tsubo: caso clínico.

Tako-Tsubo syndrome resembles an acute myocardial infarction in symptoms, laboratory parameters and electrocardiographic changes. However, angiography does not show evidence of coronary occlusion, and typically an apical ballooning of the ventricle in systole is observed. We report a 78-year-old woman with no coronary risks factors, admitted to the emergency room due to acute chestpain and an electrocardiogram compatible with an acute coronary syndrome with ST elevation. Serum troponin and creatin-kinase (MB fraction) were elevated. An emergency coronary angiography did not show a coronary occlusion. Due to the apical ballooning observed in the left ventriculography, a probable diagnosis of Tako-Tsubo was proposed. The patient had a favorable evolution. A treadmill test, echocardiogram and myocardial perfusión SPECT, performed one month later, disclosed no abnormalities.

Prevention of atrial fibrillation following cardiac surgery: basis for a novel therapeutic strategy based on non-hypoxic myocardial preconditioning.

Atrial fibrillation is the most common complication of cardiac surgical procedures performed with cardiopulmonary bypass. It contributes to increased hospital length of stay and treatment costs. At present, preventive strategies offer only suboptimal benefits, despite improvements in anesthesia, surgical technique, and medical therapy. The pathogenesis of postoperative atrial fibrillation is considered to be multifactorial. However oxidative stress is a major contributory factor representing the unavoidable consequences of ischemia/reperfusion cycle occurring in this setting. Considerable evidence suggests the involvement of reactive oxygen species (ROS) in the pathogenic mechanism of this arrhythmia. Interestingly, the deleterious consequences of high ROS exposure, such as inflammation, cell death (apoptosis/necrosis) or fibrosis, may be abrogated by a myocardial preconditioning process caused by previous exposure to moderate ROS concentration known to trigger survival response mechanisms. The latter condition may be created by n-3 PUFA supplementation that could give rise to an adaptive response characterized by increased expression of myocardial antioxidant enzymes and/or anti-apoptotic pathways. In addition, a further reinforcement of myocardial antioxidant defenses could be obtained through vitamins C and E supplementation, an intervention also known to diminish enzymatic ROS production. Based on this paradigm, this review presents clinical and experimental evidence supporting the pathophysiological and molecular basis for a novel therapeutic approach aimed to diminish the incidence of postoperative atrial fibrillation through a non-hypoxic preconditioning plus a reinforcement of the antioxidant defense system in the myocardial tissue.

Non-hypoxic preconditioning of myocardium against postoperative atrial fibrillation: mechanism based on enhancement of the antioxidant defense system.

Oxidative stress underlies postoperative atrial fibrillation and electrophysiological remodelling associated with rapid atrial pacing. An increasing body of evidence indicates that the formation of reactive oxygen species (ROS) released following extracorporeal circulation are involved in the structural and functional myocardial impairment derived from the ischemia-reperfusion cycle. ROS behave as intracellular messengers mediating pathological processes, such as inflammation, apoptosis and necrosis, thereby participating in the pathophysiology of atrial fibrillation. Thus, increased superoxide (O(2)(.-)) production has been found in isolated atrial cardiomyocytes from patients with atrial fibrillation. Therefore, it seems reasonable to assume that the reinforcement of the antioxidant defense system should protect the heart against functional alterations in the cardiac rhythm. On this line, antioxidant enzyme induction through in vivo exposure to moderate concentration of ROS is associated with a reduction in the susceptibility of myocytes to ROS-induced injury. This response could be due to a prevailing effect of survival over apoptotic pathway. Previously, tissue preconditioning caused by prior exposure to an ischemia/reperfusion cycle has been successfully applied in experimental models and clinical settings associated with oxidative damage by ROS. However, such hypoxic preconditioning method is harmful to be applied to many clinical conditions associated with oxidative stress. In turn, experimental studies have revealed that non-enzymatic antioxidants produce a significant functional amelioration in cardiomyocytes subjected to an oxidative challenge. Moreover, clinical studies with patients scheduled for primary coronary artery bypass graft surgery had a reduced incidence of postoperative atrial fibrillation. We present the hypothesis of non-hypoxic preconditioning based on the association of pretreatment with n-3 polyunsaturated fatty acids followed by ascorbate plus alpha-tocoferol supplementation diminishes the incidence of postoperative atrial fibrillation in patients subjected to cardiac surgery with extracorporeal circulation.

Diagnóstico diferencial de las taquicardias de complejo ancho: un desafío permanente / Wide QRS tachycardia: a diagnostic challenge

El diagnóstico electrocardiográfico correcto de la causa de una taquicardia de complejo QRS ancho (TCA) es fundamental, ya que tanto el manejo, como el pronóstico del paciente, es diferente según su etiología, y define el estudio que debemos realizar. Numerosos criterios y algoritmos han sido descritos para diferenciar el origen de estas taquicardias. Sin embargo, muchos de estos son complejos y difíciles de aplicar para el médico menos experimentado. Esto es particularmente importante en los servicios de emergencia, donde se necesita una definición rápida que permita un manejo agudo apropiado. En la presente revisión analizamos los diferentes mecanismos de las TCA y los principales criterios diagnósticos en el ECG, reforzando, especialmente, aquellos de aplicación rápida y de alto rendimiento diagnóstico.

The correct electrocardiographic diagnosis of the cause of a wide QRS complex tachycardia (WCT) is essential since both management and prognosis of the patient. The correct electrocardiographic diagnosis of the cause of a wide QRS complex tachycardia (WCT) is essential since both management and prognosis is different according to its etiology and defines the study that we should perform. Numerous criteria and algorithms have been described to differentiate the origin of these tachycardias. However, many of these are complex and difficult to apply to the less experienced doctor. This is particularly important in emergency rooms, where a rapid definition is needed to allow proper therapy. In this review we analyze the different mechanisms of WCT and the main EKG diagnostic criteria, emphasizing those which can be applied rapidly and have high diagnostic value.

Respuesta a la estimulación multisitio del ventrículo izquierdo en un paciente con terapia de resincronización y fibrilación auricular permanente / Multi-site stimulation of the left ventricle in a patient with dilated cardiomyopathy and permanent atrial fibrillation on resynchronization therapy

Resumen: Se presenta el caso de un hombre de 79 años con miocardiopatía dilatada severa, disfunción ventricular izquierda, fibrilación auricular permanente y portador de un resincronizador ventricular. Al efectuar un recambio del resincronizador se implantó un electrodo adicional para estimulación multisitio del ventrículo izquierdo. Ello condujo a significativa mejoría clínica y de la fracción de eyección del ventrículo izquierdo.

Abstract: A 79-year-old man with dilated cardiomyopathy and atrial fibrillation undergoing resynchronization therapy had and additional electrode implanted in the left ventricle. Multi-site stimulation led to an improved functional class and left ventricular ejection fraction.

A randomized controlled trial to prevent post-operative atrial fibrillation by antioxidant reinforcement.

OBJECTIVES: This study was designed to assess whether the reinforcement of the antioxidant system, through n-3 fatty acids plus antioxidant vitamin supplementation, could reduce the incidence of post-operative atrial fibrillation. BACKGROUND: Therapy to prevent post-operative atrial fibrillation remains suboptimal. Although oxidative stress plays a key role in the pathogenesis of this arrhythmia, antioxidant reinforcement has produced controversial results. METHODS: A total of 203 patients scheduled for on-pump cardiac surgery were randomized to placebo or supplementation with n-3 polyunsaturated fatty acids (2 g/day) (eicosapentaenoic acid:docosahexaenoic acid ratio 1:2), vitamin C (1 g/day), and vitamin E (400 IU/day). The primary outcome was the occurrence of post-operative atrial fibrillation. Secondary outcomes were the biomarkers related to oxidative stress and inflammation. RESULTS: Post-operative atrial fibrillation occurred in 10 of 103 patients (9.7%) in the supplemented group versus 32 of 100 patients (32%) in the placebo group (p < 0.001). Early after surgery, placebo patients presented with increased levels of biomarkers of inflammation and oxidative stress, which were markedly attenuated by antioxidant supplementation. The activity of catalase, superoxide dismutase, and glutathione peroxidase in atrial tissue of the supplemented patients was 24.0%, 17.1%, and 19.7% higher than the respective placebo values (p < 0.05). The atrial tissue of patients who developed atrial fibrillation showed NADPH oxidase p47-phox subunit protein and mRNA expression 38.4% and 35.7% higher, respectively, than patients in sinus rhythm (p < 0.05). CONCLUSIONS: This safe, well-tolerated, and low-cost regimen, consisting of n-3 polyunsaturated fatty acids plus vitamins C and E supplementation, favorably affected post-operative atrial fibrillation, increased antioxidant potential, and attenuated oxidative stress and inflammation. (Prevention of Post-Operative Atrial Fibrillation: Pathophysiological Characterization of a Pharmacological Intervention Based on a Novel Model of Nonhypoxic Pre-Conditioning; ISRCTN45347268).

Antioxidant therapy reduces oxidative and inflammatory tissue damage in patients subjected to cardiac surgery with extracorporeal circulation.

Ischaemia reperfusion injury is a pathophysiological event that occurs after cardiac surgery with extracorporeal circulation. This clinical event has been associated with the induction of oxidative and inflammatory damage in atrial tissue. Here, we tested whether combined omega 3 polyunsaturated fatty acids (n-3 PUFA)-antioxidant vitamin protocol therapy reduces oxidative and inflammatory cardiac tissue damage. This trial assigned 95 either-sex patients to supplementation with n-3 PUFA (2 g/day), or matching placebo groups, 7 days before on-pump surgery. Antioxidant vitamins C (1 g/day) and E (400 IU/day) or placebo were added from 2 days before surgery until discharge. Blood and atrial tissue samples were obtained during the intervention. Reduced/oxidized glutathione (GSH/GSSG) ratio, malondialdehyde (MDA) and protein carbonylation were determined in atrial tissue. Leucocyte count and high-sensitivity C-reactive protein (hs-CRP) in blood plus nuclear factor (NF)-κappaB activation in atrial tissue served for inflammation assessment. Lipid peroxidation and protein carbonylation were 27.5 and 24% lower in supplemented patients (p < 0.01). GSH/GSSG ratio was 38.1% higher in supplemented patients compared with placebo (p < 0.01). Leucocyte count and serum hs-CRP levels were markedly lower throughout the protocol in supplemented patients (p < 0.01). Atrial tissue NF-κB DNA activation in supplemented patients was 22.5% lower than that in placebo patients (p < 0.05). The combined n-3 PUFA-antioxidant vitamin protocol therapy here proposed reduced the oxidative stress and inflammation biomarkers, in patients undergoing on-pump cardiac surgery.

Use of vitamins C and E as a prophylactic therapy to prevent postoperative atrial fibrillation.

Oxidative stress has been strongly involved in the underlying mechanism of atrial fibrillation, particularly in the arrhythmia occurring in patients undergoing cardiac surgery with extracorporeal circulation (postoperative atrial fibrillation). The ischemia/reperfusion injury thus occurring in the myocardial tissue contributes to the development of tissue remodeling, thought to be responsible for the functional heart impairment. Consequently, structural changes due to the cardiac tissue biomolecules attack by reactive oxygen and/or nitrogen species could account for functional changes in ion channels, transporters, membrane conductance, cytosolic transduction signals, and other events, all associated with the occurrence of arrhythmic consequences. The lack of success and significant side effects of anti-arrhythmic drugs have given rise to attempts aimed to develop alternative novel pharmacologic treatments. On this line, the biological properties of the antioxidant vitamins C and E suggest that they could decrease the vulnerability of the heart to the oxidative damage. Nevertheless, very few studies to assess their anti-arrhythmic effects have been reported in humans. The clinical and experimental evidence supporting the view that the pharmacological use of antioxidant vitamins could contribute to prevent postoperative atrial fibrillation is presented.

Endocarditis infecciosa: características clínicas, complicaciones y mortalidad en 506 pacientes y factores pronósticos de sobrevida a 10 años (1998-2008). Estudio cooperativo nacional en endocarditis infecciosa en Chile (ECNEI-2) / Clinical characteristics, complications and mortality in 506 patients with infective endocarditis and determinants of survival rate at 10 years

Background: Rates ofmorbidity and mortality in Infective Endocarditis (IE) remain high and prognosis in this disease is still difficult and uncertain. Aim: To study IE in Chile in its active phase during inpatient hospital stay and long term survival rates. Material and Methods: Observational prospective national cohort study of 506 consecutive patients included between June 1,1998 and July 31, 2008, from 37 Chilean hospitals (secondary and tertiary centers) nationwide. Results: The main findings were the presence of Rheumatic valve disease in 22.1 % of patients, a history of intravenous drug abuse (IVDA) only in 0.7%, the presence of Staphylo-coccus aureus in 29.2% of blood cultures, negative blood cultures in 33.2%, heart failure in 51.7% and native valve involvement in 86% ofpatients. Echocardiographic diagnosis was achieved in 94% of patients. Hospital mortality was 26.1% and its prognostics factors were persisting infection (Odds ratio (OR) 6.43, Confidence Interval (CI) 1.45-28.33%), failure of medical treatment and no surgical intervention (OR 48.8; CI 6.67-349.9). Five and 10 years survival rates were 75.6 and 48.6%, respectively. The significant prognostic factors for long term mortality, determined by multivariate analysis were the presence of diabetes, Staphylococcus aureus infection, sepsis, heart failure, renal failure and lack of surgical treatment during the IE episode. Conclusions: The microbiologic diagnosis of IE must be urgently improved in Chile. Mortality rates are still high (26.1%) partly because of a high incidence of negative blood cultures and the need for more surgical valve interventions during in-hospital period. Long term prognostic factors for mortality should be identified early to improve outcome.

Hospitalizaciones asociadas al diagnóstico de fibrilación auricular en Chile: tendencia creciente en la última década / Hospitalization for atrial fibrillation in Chile: a growing tendency in the last decade

Antecedentes: Publicaciones internacionales señalan que las hospitalizaciones por fibrilación auricular (FA) están aumentando, lo que tiene importantes implicaciones para la salud pública y el cardiólogo. En Chile no se dispone de mayor información sobre el problema. Objetivo: Estudiar las hospitalizaciones asociadas al diagnóstico de FA en Chile. Métodos: Los egresos hospitalarios con el diagnóstico de FA fueron obtenidos del Ministerio de Salud (código 1 48 FA) de la Clasificación Internacional de Enfermedades. Hubo datos disponibles solo para los años 2002 al 2007; se analizó género, grupos etarios y regiones del país. Las tasas (T) de egresos hospitalarios con este diagnóstico por 10.000 habitantes (H) fueron calculadas en base a la población proyectada del último censo nacional para los años señalados. Para el análisis estadístico se utilizó el test de proporsiones de Z. Resultados: La T total de egreso hospitalario asociada al diagnóstico de FA el año 2002 fue de 2,2/10.000 H la que aumentó gradualmente hasta una T de 2,8/10.000 H el año 2007 (P<0,001). Las T de hombres y mujeres el año 2002 fueron de 2,2 y 2,1 y aumentaron hasta 2,8 y 2,7/10.000 H el 2007, respectivamente (P<0,001). En el grupo etario <40 años no se observaron mayores variaciones de las T entre los años 2002 y 2007 (P<0,01). En los mismos períodos las T en pacientes de 40-64 años fueron de 2,9 y 3,6/10.000 H, entre 65-79 años 14,2 y 18,5/10.000 H (P<0,001), mientras que en >80 años las T fueron de 32,4 y 43,7/10.000 H respectivamente (P<0,0001). En las regiones I-II-III, las T no presentaron variaciones, pero en las regiones X-XII-XII las T aumentaron gradualmente en el periodo estudiado (2,3 y 3,5 /10.000 H los años 2002 y 2007, respectivamente). Conclusiones: Este trabajo muestra que en nuestro país, las H por FA muestran una tendencia creciente, con un incremento de 27 percent en el periodo estudiado, especialmente en > 65 años, y en las regiones del sur del país...

Background: Hospitalization for atrial fibrillation (AF) is reported to be increasing worldwide, becoming a cardiovascular health problem. Scarce data on this subject is available in Chile. Aim: To describe hospitalizations related to AF in Chile. Method: The discharge diagnosis of AF (ICD I48)was obtained form the Ministry of Health reports. Only data from 2002 through 2007 was available. Gender, age and location (regions) were analyzed. A projection derived form the last population census was used to estimate rates per 10.000 people discharged with a diagnosis of AF Results: The rate of discharges with a diagnosis of AF increased from 2.2 per 10.000 in 2002 to 2.8 per 10.000 in 2007. Male and female rates were 2.2 and 2.1 respectively in 2002, increasing to 2.8 and 2.7 in 2007. The rate of AF discharge remained approximately constant for those under 40 years of age. In contrast, the corresponding rates for 2002 and 2007 increased from 2.9 to 3.6 for those aged 40-64, 14.2 to 18.5 for those aged 65-79 and 32.4 to 43.7 for those over 80. AF discharge rates did no vary in Regions I to III while they increased from 2.3 to 3.5 in regions X to XII. Conclusion: The rate of discharge with a diagnosis of AF has increased in Chile approximately 25 percentfrom 2002 to 2007. This phenomenon is more marked in those over 65 years of age and those living in the southern regions of the country.

Síndrome de Tako-Tsubo: caso clínico / Tako-Tsubo syndrome: Report of one case

Tako-Tsubo syndrome resembles an acute myocardial infarction in symptoms, laboratory parameters and electrocardiographic changes. However, angiography does not show evidence of coronary occlusion, and typically an apical ballooning ofthe ventricle in systole is observed. We report a 78-year-old woman with no coronary risks factors, admitted to the emergency room due to acute chestpain and an electrocardiogram compatible with an acute coronary syndrome with ST elevation. Serum troponin and creatin-kinase (MB fraction) were elevated. An emergency coronary angiography did not show a coronary occlusion. Due to the apical ballooning observed in the left ventriculography, aprobable diagnosis of Tako-Tsubo was proposed. The patient had a favorable evolution. A treadmill test, echocardiogram and myocardial perfusión SPECT, performed one month later, disclosed no abnormalities.

[Results of intraventricular resynchronization in patients with severe cardiac failure]. / Resultados clínicos de la resincronización ventricular en pacientes con insuficiencia cardíaca severa.

BACKGROUND: Intraventricular resynchronization with pacemakers is a promising therapy for patients with refractory cardiac failure and intraventricular conductions delay. However its long term effects are not well known. AIM: To report the results of this therapy in patients with cardiac failure. PATIENTS AND METHODS: Fourteen patients (11 male), whose mean age was 68 years, with a severe and refractory cardiac failure, have been treated in our unit using intraventricular resynchronization with pacemakers. Eight had a coronary heart disease and six a dilated myocardiopathy. The pacemaker was implanted transvenously, with conventional stimulation in atrium and right ventricle. The left ventricle was stimulated through an epicardial vein, accessed through the coronary sinus. RESULTS: In one patient the high thresholds did not allow a left ventricular stimulation. In the other 13 patients, a clinical improvement was observed in 11 (85%), that has been sustained for a mean of 8.2 months. The ejection fraction improved form 23.5 to 32.4% (p < 0.001), the 6 min walking test improved from 347 to 437 m (p = 0.003) and the functional capacity changes from 3.3 to 2.7 (p < 0.001). Three patients died during follow up. One was the patient in whom the stimulation failed and two had a sudden death. No complications of the procedure were observed. CONCLUSIONS: In this series, intraventricular resynchronization with pacemakers was effective in 11 of 13 patients, improving functional capacity and ejection fraction. Sudden death could be avoided adding a defibrillator to the pacemaker system.

Amiodarona en alta dosis de carga oral única: parámetros farmacocinéticos en pacientes sometidos a cirugía coronaria / High loading dose of amiodarone: pharmacokinetics in patients undergoing coronary

Antecedentes: Amiodarona (A) es la droga antiarrítmica más utilizada en la actualidad. No obstante, algunos aspectos de su compleja farmacología son todavía poco conocidos en ciertos grupos de pacientes. Objetivo: Estudiar los parámetros farmacocinéticos de A después de una alta dosis de carga oral en pacientes (P) sometidos a cirugía coronaria. Métodos: Cuarenta y tres P sometidos a cirugía coronaria recibieron una dosis oral de 30 mg/kg en dosis fraccionada como tratamiento profiláctico de arritmias en el post operatorio. Las concentraciones sanguíneas de la droga fueron medidas a tiempos sucesivos, por HPLC, hasta las 96 h de su administración. En base a la curva obtenida de concentración sanguínea vs tiempo, los parámetros farmacocinéticos fueron calculados mediante un programa computacional independiente del modelo compartimental. Resultados: La concentración sanguínea de A alcanzó un valor máximo de 2,3 +/- 1,5µg/ml a las 10 h de la administración de la droga. Posteriormente, se observó un descenso gradual con un valor de 0,4 +/- 0,1 µg/ml a las 96h de administración. Los parámetros farmacocinéticos obtenidos fueron: Vida media 29,1 +/- 11,3h; Area bajo la curva 0’96 63,6 +/- 22,3 (µg/ml)h; Clearance total 6,1 +/- 2,2 ml/min/kg; Volumen de distribución 15,6 +/- 5,4 L/kg. Conclusiones: La farmacocinética de A presenta diferencias con lo encontrado en estudios de dosis única en otros grupos de pacientes. El presente trabajo puede servir para esquemas de dosificación menos empíricos de A.

Background: Amiodarone is currently the most commonly used antiarrhythmic drug. However, some aspects of its complex pharmacokinetics in particular groups of patients are not well known. Aim: to study the pharmacokinetics of amiodarone after a high loading oral dose in patients undergoing coronary revascularization surgery. Methods: Forty three patients operated on for coronary artery disease received oral dose amiodarone, 30mg/Kg, in a fractioned dose as a prophylactic antiarrhythmic medication following surgery. Blood amiodarone concentration was measured at successive intervals for 96 hr. A software based on a non compartmental model was used to determine pharmacokinetic parameters. Results: Maximal blood concentration of amiodarone was 2.3 +/-1.5µg/ml 10hr after drug administration. A subsequent gradual decrease of amiodarone blood level was observed, down to 0.4 +/- 0.1µg/ml at 96hr post drug administration. The half-life time was 29.1 +/- 11.3hr. The area under de 0 to 96hr curve was 63.6 +/- 22.3µg/ml.Total clearance was 6.1 +/- 2.2 ml/min/kg. The distribution volume was 15.6 +/- 5,4 L/kg. Conclusion: Pharmacokinetics of amiodarone differs from that obtained following a single dose in other groups of patients. The data provided may be used to determine more objective amiodarone dosing schemes.