ABSTRACT: This is a biographical note on Bernard Lown MD, recently deceased. He was one of the foremost cardiologist in the XXth century. Relevant were his studies on ventricular arrhythmias and myocardial ischemia, as well the effect of mental stress in lowering the ventricular arrhythmia threshold. Along with European researchs he developed the electric cardiovertor. Special emphasis is placed on his skills as a clinician and is humane approach to patient care. He contributed to international efforts to prevent nuclear war. For this effort he was awarded, along with Dr Chazov, the Nobel Peace Price.

RESUMEN: Se presenta una semblanza del Dr. Bernard Lown, uno de los más destacados cardiólogos del siglo XX. Muy relevantes fueron sus estudios sobre arritmias ventriculares e isquemia miocárdica, como también la influencia del estrés sobre el umbral de la fibrilación ventricular. Simultáneamente con otros investigadores europeos desarrolló el cardiovertor eléctrico. Se releva particularmente su condición de gran clínico y el trato humano con sus pacientes. Finalmente, se destaca su contribución a evitar una guerra nuclear por lo cual, junto al Dr Chazov, recibió el Premio Nobel de la Paz.

Abstract In Chile, important advances have been made in the management of Acute Myocardial Infarction (MI) with ST segment elevation (STEMI). Due to the progress in early diagnosis and treatment, particularly with the increase in Primary Angioplasty (Primary PCI), nowadays there are conditions to improve early management through the combination of reperfusion strategies and the implementation of MI reperfusion networks. The present article reviews the evidence justifying the promotion of this strategy and outlines possible actions to achieve it.

Resumen En Chile, se han logrado avances importantes en el manejo del Infarto Agudo de Miocardio (IAM) con elevación del segmento ST (IAMCEST). Debido a la mejoría en el diagnóstico precoz y tratamiento, particularmente, con el incremento de la Angioplastía Primaria (APP), hoy están dadas las condiciones para seguir progresando por la vía de la combinación de estrategias de reperfusión y la creación de Redes de Manejo del IAM. El siguiente artículo revisa la evidencia que justifica impulsar dicho avance y se esbozan posibles caminos para lograrlo.

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with high rates of death, ischemic stroke and systemic embolism (SE). There is scarce information about clinical characteristics and use of anti-thrombotic therapies in Chilean patients with non-valvular AF. Aim: To describe the characteristics and 1-year outcomes of patients with recently diagnosed AF recruited in Chile into the prospective global GARFIELD-AF registry. Material and Methods: Between 2011-2016, we prospectively registered information of 971 patients recruited at 15 centers, 85% of them from the public system and 15% from the private sector. Demographics, clinical characteristics and use of antithrombotic therapies were recorded for all patients. Adverse clinical outcomes were analyzed in 711 patients with 1-year follow-up. Results: The mean age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral anticoagulants were prescribed in 82% of patients. Seventy percent received Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy and only 8% did not receive any antithrombotic therapy. Mean time in optimal therapeutic range (an international normalized ratio of 2 to 3), was achieved in only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40 (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up. Conclusions: Although the use of vitamin K antagonists at baseline was high, the mean time in optimal therapeutic range was low. Mortality and stroke rates are higher than those reported in other contemporary registries.

Background: Cardiovascular rehabilitation (CVR) has been shown to improve functional capacity (FC) and quality of life. The relation between these aspects has been scarcely reported in Chile. Objectives: 1) To determine the impact of the CVR phase II program on quality of life as measured by the SF36 survey and 2) to determine which patient related factors can influence this relationship. Method: Prospective study in subjects who completed 36 sessions of an RCV and Secondary Prevention program (PREV2). Medical records, cardiovascular risk factors (CV), anthropometric parameters, health forecast, functional capacity (FC) (determined by meters walked on 6-minute Walking test-TM6) and SF36 scores were recorded at the beginning and end of the CVR. Results: Data on 277 subjects (78% men, age 59 years) was analyzed. There was a significant improvement in: a) walking meters (final / initial difference = 56 meters, p <0.0001), b) physical health score (68 vs 79, p <0.0001), c) emotional health (68 vs 78, p <0.0001) of the SF36. The men walked more meters (p <0.0001). There was a significant association between delta TM6 final-initial and SF36 final-initial only for physical health (p <0.01). For an increase of 10 meters walked in the final TM6, SF36 score for physical health increased 0.38 points in men ad 1.52 in women. Improvement in emotional health was significantly associated only with changes in physical health (p <0.0001). Conclusion: Patients attending a phase II cardiovascular rehabilitation program significantly improve their aerobic capacity, and their perception of physical and emotional health.

Antecedentes: La rehabilitación cardiovascular (RCV) ha demostrado mejorar la capacidad física (CF) y la calidad de vida. La relación de estos aspectos ha sido escasamente reportada en Chile. Objetivos: 1) Determinar el impacto de la RCV fase II sobre la calidad de vida, medida por la encuesta SF36 y, 2) determinar qué factores, relacionados con el paciente, pueden incidir en esta relación. Método: Estudio prospectivo en sujetos que completaron 36 sesiones de un programa de RCV y Prevención Secundaria (PREV2). Se registraron al ingreso y final de la RCV: antecedentes médicos, factores de riesgo cardiovascular (CV), parámetros antropométricos, previsión de salud, CF (determinada por los metros caminados en test de marcha de 6 minutos-TM6) y puntaje en la encuesta SF36. Resultados: 277 sujetos (78% hombres, edad 59 años). Hubo una mejoría significativa en: a) los metros caminados (diferencia final/inicial= 56 metros, p<0.0001), b) puntaje de salud física (68 vs 79; p<0.0001), c) salud emocional (68 vs 78, p<0.0001) del SF36. Los hombres caminaron más metros promedio (p<0.0001). Hubo una asociación significativa entre los deltas del TM6 final-inicial y SF36 final-inicial, sólo para salud física (p<0.01). Por un aumento de 10 metros caminados en el TM6 final se incrementa el puntaje de la SF36 para salud física (Hombres: 0.38/ Mujeres: 1.52). La mejoría en la salud emocional sólo se asoció significativamente con los cambios en la salud física (p<0.0001). Conclusion: Los pacientes que asisten a un programa de RCV mejoran significativamente su capacidad aeróbica, y su percepción de salud física y emocional.

An 84-year man with prior coronary artery bypass surgery and endovascular repair of an abdominal aortic aneurysm developed congestive heart failu-re. He had calcific aortic valve disease with severe regurgitation. A #29 Edwards-Sapien aortic valve via trans-apical approach was implanted with the patient connected to extra corporeal circulation. The patient recovered successfully and remained in functional class II 8 months after hospital dis-charge.

Introduction: Atrial myopathy and fibrosis constitute a pro-arrhythmic and pro-thromboembolic substrate in patients with atrial fibrillation (AF). Recent studies using left atrial strain (LAS) have shown that LAS contributes to predict AF recurrence in patients with paroxysmal AF. The association between LAS and cardiac biomarkers in predicting silent stroke (SS) in patients with new AF has not been studied. Aim: The association of LAS and cardiac biomarkers contribute to predict SS in patients with new AF. Methods: We have prospectively evaluated 57 consecutive patients with new AF (first episode with less than 8 weeks of evolution). Baseline clinical characteristics and blood samples for determinations of Pro-BNP, D-Dimer and GDF-15 were obtained. Brain magnetic resonance (BMRI) and 2D Echo were performed within 3 days. In sinus rhythm, the positive deflection during ventricular systole of the LAS curve derived from speckle tracking was considered (mean of 5 cycles) (LASS). Mann Whitney U test and Spearman Rho were used for statistical analysis. Results: Mean age was 70±8,2 years, 70% were men. The mean CHA2DS2-VASc score was 3,1±1. Mean pro-BNP, D-Dimer and GDF-15 were 96,1±12,4 pg/ml, 990±140 ng/ml and 12 ng/ml, respectively. Fifteen percent of patients (n=9) had evidence of previous SS in BMRI. Patients with SS had significantly less LASS than patients without events (5,5±1,1% and 14,6±7,3% respectively p=0,04). In addition, a significant correlation between LASs and pro-BNP, D-Dimer and GDF-15 was found. Conclusion: Evidence of SS was found in 15% of patients with new AF. This was associated with LASs impairment, which was inversely correlated with cardiac biomarkers of LV overload, thrombogenesis and LA fibrosis. These findings could be utilized for a better risk stratification of stroke in patients with new AF.

Introducción: La miopatía y fibrosis auricular representan el sustrato protrombótico y proarrítmico en pacientes con fibrilación auricular (FA). Estudios recientes muestran relación entre el strain auricular izquierdo (SAI), eventos cardiovasculares y recurrencia en pacientes con FA. La asociación entre SAI y bio-marcadores cardíacos como predictores de accidente cerebrovascular silente (ACVs) en pacientes con FA de reciente comienzo (FArc) no ha sido estudiada. Objetivo: Determinar si la asociación entre SAI y biomarcadores cardíacos contribuye a la predicción de ACV en pacientes con FArc. Métodos: Se realizó un estudio prospectivo que permitió reclutar 57 pacientes con FArc (primer episodio de < de 8 semanas de evolución). Obtenido consentimiento informado (CI) se realizó recolección de datos clínicos y muestras de sangre para determinación de Pro-BNP, Dimero-D y GDF-15. Se realizó resonancia nuclear magnética cerebral (RNMc) y ecocardiograma transtorácico (ETT) durante los primeros 3 días de inclusión y en ritmo sinusal. Para la evaluación de SAI se consideró la curva de deflexión positiva durante la sístole ventricular (SAIs), derivada de speckle tracking, considerando el promedio de 5 ciclos. Se utilizó Mann Whitney U test y Spearman Rho para análisis estadístico. Resultados: La edad promedio fue 70±8,2 años y el 70% fueron hombres. El CHA2DS2-VASc score promedio fue 3,1±1 y el promedio de pro-BNP, Di-mero-D y GDF-15 fue 96,1±12,4 pg/ml, 990±140 ng/ ml y 12 ng/ml respectivamente. 15% de los pacientes (n=9) presentaban ACVs en la RNMc al momento del diagnóstico. Se observó, además, que los pacientes con ACV presentaban un SAIs más bajo que los pacientes sin eventos (5,5±1,1% y 14,6±7,3% respectivamente p=0.04). Adicionalmente, se encontró una correlación significativa entre SAIs y pro-BNP, Dimero-D y GDF-15. Conclusiones: En este trabajo se evidenció que el 15% de los pacientes con FArc presenta ACVs al momento del diagnóstico. El SAIs bajo se correlaciona de forma inversa con los biomarcadores de sobrecarga, trombogénesis, fibrosis auricular y presencia de ACV silente. Estos resultados pueden ser utilizados para una mejor estratificación del riesgo de ACV en pacientes con FA.

Background: Atrial fibrillation (AF) generates a hypercoagulable state with an increased thrombin generation and raised levels of thrombin-antithrombin complexes, which results in a high risk of stroke and thromboembolism. Aim: To evaluate the anticoagulant effect of rivaroxaban by anti-Xa factor activity and its correlation with thrombin-antithrombin complexes, thrombin generation and prothrombin time in patients newly diagnosed with non-valvular AF. Patients and Methods: Prospective study in patients with indication of anticoagulation. Demographic variables, cardiovascular risk factors, CHA2DS2-VASc and HAS-BLED scores were recorded. Blood samples were taken at baseline, at 3 and 24 hours after the administration of the drug and at 30 days. Rivaroxaban levels, anti-Xa activity, prothrombin time, thrombin generation and plasma levels of thrombin-antithrombin complexes were determined. Results: We studied 20 patients aged 76.3 ± 8.0 years (60% female) with a CHA2DS2-VASc score > 2 points. The anti-Xa factor activity correlated with rivaroxaban plasma levels at 3 hours (r = 0.61, p < 0.01), at 24 hours (r = 0.85, p < 0.01) and at 30 days (r = 0.99, p < 0.01), with prothrombin time at 3 hours (r = -0.86, p = 0.019) and at 30 days (r = -0.63, p = 0.02) and with a sustained decrease in thrombin generation at 30 days of follow-up (r = -0.74, p < 0.01). There was no correlation with thrombin-antithrombin complexes (r = -0.02, p = 0.83). Conclusions: Rivaroxaban consistently inhibited the mild pro-coagulant state found in newly diagnosed non-valvular AF patients through the first 24 hours and this effect was maintained at 30 days. Plasma levels of the drug correlated with anti-Xa factor activity, thrombin generation and prothrombin time

Background: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. Aim: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. Material and Methods: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. Results: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. Conclusions: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

Background: Socioeconomic status is associated with cardiovascular mortality. Aim: To evaluate the effect of educational level, on the prognosis of patients with acute myocardial infarction in Chile. Material and Methods: Cohort study of 3,636 patients aged 63.1 ± 13.2 years, 27% women, hospitalized in 16 centers participating in the Chilean Myocardial Infarction Registry (GEMI) between 2009 and 2012. Vital status was obtained from the National Mortality Database. Patients were divided, according to educational level, in four groups, namely none (no formal education), basic (< 8 years), secondary (8-12 years) and tertiary (> 12 years). Crude and adjusted (age, sex, cardiovascular risk factors and treatments) hazard ratios (HR) were estimated using Cox regression models. Results: The distribution by educational level was 3.2% none, 31.8% basic, 43.0% secondary and 22.0% tertiary. During a median follow-up period of 22 months (interquartile range 11-37 years), 631 patients died (17.3%), of whom 198 died during hospitalization (5.5%). The 30 day case-fatality rate according to educational level was 3.4% in tertiary, 4.7% in secondary, 11.9% in basic, 19.1% in none (p < 0.0001). Among patients surviving the first 30 days, the case-fatality rate was 4.4%, 8.6%, 14.6% and 27.0%, respectively (p < 0.0001). The increased risk of death for groups with lower education compared with individuals with tertiary education, persisted in the multivariate analysis with a hazard ratio for secondary education 1.58 (95% confidence intervals (CI), 1.18-2.10); for basic education 1.90 (95% CI, 1.41-2.47) and for none 3.50 (95% CI, 2.35-5.21). Conclusions: A lower educational level was associated with a worse prognosis in patients with myocardial infarction, even after controlling for potential confounding factors.

Background: Patients with cardiac mechanical valves (MHV) represent a significant proportion of all patients requiring anticoagulation. However, there are few studies comparing safety and efficacy of different vitamin K antagonists (VKA). Aim: To compare the efficacy and safety of warfarin and acenocoumarol in patients with MHV. Methods: Observational study of patients who had a mitral and /or aortic valve replacement between 2005 and 2013, followed at the Catholic University anticoagulation clinics. VKA dose adjustments were performed using the Isaza Hytwin Biostac 2.0 software. Major and minor bleeding (safety) and stroke and systemic embolism (effectiveness) were evaluated. The efficacy was estimated by the time in therapeutic range (TTR) with the Rosendaal method. Results: 365 patients were included with a mean age of 64.1 ± 13.2 years, 53.9% of them were females. Mean follow-up was 33.3 ± 18 months Overall mortality rate was 2.1%, which is similar to that of patients treated with VKA for other reasons. The average TTR was 68 ± 13.3% (66,1 ± 12,6% for aortic valves, 65,8 ± 13,8% for mitral valves and 61,2 ± 12% for aortic and mitral valves). TTR was lower with acenocoumarol compared to warfarin (65.1 ± 13.1 vs. 71.2 ± 13.6 , p = 0.001 ), However, the risk of complications was not different between groups. Conclusions: Although warfarin provides a better profile of TTR , there were no significant differences in efficacy or safety when compared with acenocoumarol.

Introducción: Los pacientes con válvulas mecánicas cardíacas (VMC) representan una proporción significativa del total de pacientes que requieren anticoagulación. Sin embargo, hay pocos estudios que comparen la efectividad de la anticoagulación con distintos antagonistas de vitamina K (AVK). Objetivo: Comparar la efectividad y seguridad del tratamiento con warfarina y acenocumarol en pacientes con VMC. Métodos: Estudio observacional de pacientes en po-liclínico de anticoagulación UC sometidos a recambio valvular entre los años 2005 y 2013. Se estandarizó las dosis de AVK con software Isaza Hytwin Biostac 2.0. Se evaluaron registros de hemorragia mayor y menor (seguridad) y accidentes vasculares y embolías sistémicas (efectividad). La efectividad se analizó mediante el tiempo en rango terapéutico (TTR) con método de Ro-sendaal. Resultados: Se incluyó 365 pacientes con edad promedio de 64,1 ± 13,2 años, 53,9% de sexo femenino. El seguimiento promedio fue de 33,3 ± 18 meses; La mortalidad registrada fue 2,1%. El promedio de TTR fue 68 ± 13,3% (recambio aórtico TTR 66,1 ± 12,6%, recambio mitral TTR 65,8 ± 13,8% y recambio mitro-aórtico TTR 61,2 ± 12%). Acenocumarol presentó un TTR menor que warfarina (65,1 ± 13,1 vs. 71,2 ± 13,6, p = 0,001), sin aumento del riesgo de complicaciones. Conclusión: Aunque warfarina ofrece un mejor perfil de TTR, no existen diferencias significativas en la eficacia o seguridad al compararla con acenocumarol.

Exercise and cardiac rehabilitation are indications with type I A evidence in most secondary cardiovascular prevention guidelines. Rehabilitation programs not only include exercise but also provide integral care and education about cardiovascular risk factors. However there is a paucity of such programs in Chile. Moreover there is a lack of awareness about the benefits of exercise and there is lack of knowledge about the details of exercise prescription in secondary prevention. Therefore, the divulgation of this knowledge is of utmost importance.