Experiencia inicial con el uso de trombolisis local asistida por catéter de ultrasonido terapeútico (EKOSonic®) en pacientes con tromboembolismo pulmonar agudo / Use of local thrombolysis associated to therapeutic ultrasound (EKOSonic) in patients with acute pulmonary thromboembolism: a preliminary experience

INTRODUCCIÓN: El tromboembolismo pulmonar (TEP) es una causa frecuente de morbimortalidad cardiovascular y la trombolisis local asistida por ultrasonido (TLUS) constituye una alternativa de tratamiento validada para pacientes de riesgo intermedio. No existen reportes del uso de esta tecnología en el ámbito nacional. MÉTODOS: Análisis descriptivo, prospectivo, sobre una serie de pacientes con TEP agudo, de riesgo intermedio, tratados en forma percutánea con trombolisis local asistida por catéter de ultrasonido terapéutico (EKOSonic®). Se analiza la eficacia y seguridad del procedimiento mediante variables clínicas, hemodinámicas y radiológicas, así como desenlaces intra hospitalarios. Se reporta, además, el seguimiento a 30 días. RESULTADOS: Entre Junio de 2019 y Marzo de 2020, 4 pacientes con TEP de riesgo intermedio fueron tratados con esta técnica. El score PESI (Pulmonary Embolism severity Index) promedio era de 79,5 + 6,1. Dos pacientes requirieron la instalación de 2 catéteres para efectuar terapia bilateral. Se observó una reducción promedio en la presión sistólica de arteria pulmonar de 29% y en 3 de los 4 enfermos se logró revertir la dilatación ventricular derecha presente al ingreso. La carga trombótica se redujo en un 20% medido por score CTOI. No hubo complicaciones intraoperatorias ni intrahospitalarias asociadas a la intervención. CONCLUSIONES: En esta serie inicial, el uso de la trombolisis local con catéter de ultrasonido en pacientes con TEP de riesgo intermedio fue segura y efectiva. Los resultados perioperatorios y a 30 días fueron comparables a los descritos en experiencias internacionales; sin embargo, aún se requieren de estudios con mayor número de pacientes para confirmar los beneficios de esta técnica en nuestro medio.

BACKGROUND: Pulmonary thromboembolism (PE) is a common cause of cardiovascular morbidity and mortality and local ultrasound-assisted thrombolysis (USAT) is a validated alternative treatment for intermediate-risk patients. There are no reports on the use of this technology in our country. METHODS: Prospective series of patients with acute, intermediate-risk PE treated percutaneously with therapeutic ultrasound catheter-assisted local thrombolysis (EKOSonic®). The efficacy and safety of the procedure were analyzed using clinical, hemodynamic, and radiological variables, as well as intra-hospital outcomes. The 30-day follow-up is also reported. RESULTS: between June 2019 and March 2020, a total of 4 patients with intermediate-risk PE were treated with this technique. The average PESI score was 79.5 + 6.1. Two out of 4 patients required the use of 2 catheters for bilateral therapy. The average reduction in systolic pressure of the pulmonary artery was 29% and 3 patients reversed the right ventricular dilation present at admission. The thrombotic burden was reduced by 20% according to the Computed Tomography Obstruction Index (CTOI). There were no intraoperative or in hospital complications associated with the intervention. CONCLUSION: In this initial series, the use of local thrombolysis with an ultrasound catheter in patients with intermediate-risk PE was safe and effective. The perioperative and 30-day outcomes were similar to those previously reported in international series. However, larger randomized trials are needed to confirm this potential benefit.

Menores niveles circulantes del péptido vasoactivo y cardioprotector angiotensina-(1-9) en pacientes con hipertension arterial pulmonar / Lower circulating levels of angiotensin-(1-9), a vasoactive and cardio-protective peptide in patients with pulmonary artery hypertension

RESUMEN: Introducción: La vía clásica del sistema renina-angiotensina (SRA) está activado en pacientes con hipertensión arterial pulmonar (HAP). Previamente, hemos encontrado que en la disfunción ventricular post infarto al miocardio experimental la activación del eje clásico del SRA, dado por la enzima convertidora de angiotensina I (ECA) y angiotensina (Ang ) II se correlaciona negativamente con el eje paralelo del SRA dado por la ECA homóloga (ECA2) y el péptido vasoactivo y cardioprotector Ang-(1-9). Resultados preclínicos muestran la eficacia de la administración de Ang-(1-9) en el tratamiento del remodelamiento cardiovascular patológico. Hasta la fecha no existen antecedentes de los niveles circulantes de Ang-(1-9) en pacientes con hipertensión arterial pulmonar comparados con sujetos sanos. Objetivo: Determinar los niveles circulantes del péptido vasoactivo y cardiprotector Ang-(1-9) en pacientes con HAP y compararlos con sujetos sanos pareados por edad y sexo. Métodos: Estudio comparativo transversal en pacientes con HAP (grupo I, OMS) con presión de arteria pulmonar media (mPAP) ≥25 mmHg bajo tratamiento con furosemida (40%), espironolactona (53%), Acenocumarol/Warfarina (47%), Bosentan/Ambrisentan (27%), Sildenafil (80%), iloprost (7%) y digoxina (13%). Los sujetos controles correspondieron a sujetos asintomáticos sanos sin enfermedad cardiovascular, cardiopatía estructural ni pulmonar (n=14). En todos los pacientes se determinó mPAP, proBNP, resistencia vascular pulmonar (RVP, WU), presión capilar pulmonar (PCP, mmHg), gasto cardíaco (L/min), capacidad funcional por test de caminata 6 minutos (TC6M), cambio del área fraccional del ventrículo derecho VD (FAC, %). Se utilizó prueba t de Student y programa estadístico SPSS10.0. Un valor de p < 0,05 fue considerado como estadísticamente significativo. Resultados: Los pacientes ingresados al estudio mostraron: etiología de la HAP, idiopática (86,7%), VIH (13,3%), capacidad funcional I (6,2%), II (68,3) y III (25%) y promedio mPAP 51,3±1,9. Pacientes con HAP (grupo I, OMS) versus sujetos sanos mostraron disminución significativa de FAC, actividad plasmática de la ECA2 y niveles circulantes de Ang-(1-9). En la vía clásica del RAAS pacientes con HAP mostraron mayor actividad plasmática de ECA y niveles circulantes e Ag II. Correlaciones significativas se encontraron entre niveles de Ang-(1-9) y mPAP (r = -0.701, p < 0,001) y Ang-(1-9) vs FAC (r = 0.549, p < 0,01). Conclusiones: En pacientes con HAP (grupo I, OMS), los niveles circulantes de Ang-(1-9) están significativamente disminuidos y se asocian inversamente con la PAP, severidad del remodelamiento y disfunción del ventrículo derecho. El uso terapéutico de Ang-(1-9) como agente vasodilatador y cardioprotector podría ser relevante y potencialmente útil, desde una perspectiva clínica, en la HAP. Ang-(1-9) podría reducir la PAP y mejorar el remodelamiento vascular y del ventrículo derecho en la HAP. Por lo tanto, este péptido podría ser útil como blanco terapéutico en la HAP.

ABSTRACTS: Classic renin-angiotensis pathway (RAP) is activated in patients with pulmonary artery hypertension (PAH). We have previously shown that in patients with post myocardial infarction systolic dysfunction the activation of RAP mediated by angiotensin converting enzyme (ACE) and angiotensin II (Ang II) is inversely correlated with the parallel RAP axis mediated by homologous ACE (ACE2) and by the vasoactive and cardioprotective peptide Ang-(1-9). Pre clinical studies show that administration of Ang-(1-9) leads to a favorable ventricular remodelling. At present there is no information regarding levels of Ang-(1-9) in PAH patients compared to healthy subjects. Methods: 16 PAH patients (WHO group 1), with mean PA pressure > 25mmHg being treated with furosemide (40%), Bosentan/Ambrisentan (27%), Sildenafil (80%), iloprost (7%) were compared with healthy subjects (n=14). mPAP, pro BNP, pulmonary vascular resistance (Wu), pulmonary capillary pressure (PCP mmHg), cardiac output (L/min), functional capacity (6 min walking test) (6mWT), and changes in right ventricular fractional area (RV FA), were measured in all subjects. Results: In HAP subjects, the eiotology of PAH was unknown in 87%, or HIV (13%). Functional class was I (6.2 %), II (68.3%) or III (25%). Mean PAP was 51.3±1.9. Compared to healthy subjects, PAH patients had significantly lower RV FA, ACE2 and Ang-(19) levels. Also they had greater ACE plasma activity and AngII circulating levels. Significant correlations were found between Ang-(1-9) and mPAP (-0.701, p < 0,001) and between Ang-(1-9) and RV FA (r = 0.549, p < 0,01). Conclusion: group I PAH subjects, circulating levels of Ang-(1-9) are significantly lower than in healthy subjects and are inversely related to PAP, severity of ventricular remodeling and right ventricular dysfunction. The use of Ang-(1-9) as a vasodilator and cardioprotector agent could be clinically useful in PAH subjects.

En el modelo preclínico de insuficiencia cardíaca por disfunción sistólica en ratón (coartación de aorta torácica) la velocidad de flujo carotídeo determinada precozmente se asocia a función ventricular izquierda tardía / Carotid flow velocity is associated to late ventricular function in mice with preclinic systolic dysfunction induced by thoracic aortic coarctation

Resumen: Los modelos experimentales de falla cardíaca con fracción de eyección disminuida en murinos son pocos. Uno de estos modelos es el de coartación de la aorta torácica en el arco aórtico (COA) en ratones. Un aspecto importante en su desarrollo es la evaluación precoz del procedimiento y su relación con la función sistólica posterior. En este sentido, las velocidades de flujo carotídeo y la relación entre ambos flujos (derecho, pre-coartación; izquierdo post coartación) pueden permitir evaluar tempranamente la precisión del procedimiento y relacionarse más tardíamente con la función sistólica VI. Nuestro objetivo fue comparar precozmente (semana 2 post operatoria) las velocidades de flujo en ambas carótidas (Doppler continuo) y tardíamente (semana 5 postoperatoria) la función sistólica VI (Ecocardiograma de superficie) en ratones seudocoartados o sham (n= 6) vs ratones COA (n = 12). Se confirmó una diferencia estadísticamente significativa en la relación de velocidades de flujo entre ambas carótidas medida precozmente entre los ratones sham y COA (1,1 ± 0,1 vs 2,5 ± 0,5, p< 0,001), lo que se correlacionó con un deterioro significativo de la función sistólica del ventrículo izquierdo evaluada a las 5 semanas en los ratones COA. Conclusión: En este modelo preclínico de falla cardíaca por sobrecarga de presión con fracción de eyección VI disminuida en ratón, el aumento precoz de la velocidad de flujo en la arteria carótida derecha (pre-coartación en el modelo COA) y sobre todo de la relación entre las velocidades de flujo carotídeo entre ambas carótidas se asocia a deterioro importante de la función sistólica VI cinco semanas después de efectuada la COA, lo que permite predecir la efectividad del procedimiento en este modelo experimental.

Abstract: There are few experimental models of heart failure with reduced ejection fraction in murines. One of these models is transverse aortic coarctation (TAC) in mice. However, an important challenge in its development is the early evaluation of the procedure and its relationship with late systolic LV function. In this sense, carotid flow velocities and the relationship between both (right, precoarctation, left post-coarctation) may allow early evaluation of the accuracy of the procedure and be related to late LV systolic function. The aim was to compare early (week 2 post-operative) flow velocities determined in both carotid arteries (by continuous Doppler) with late (week 5 postoperative) LV systolic function (by echocardiogram) in sham (n= 6) vs. TAC (n: 12) mice. We confirmed a statistically significant difference in the early ratio of carotid flow velocities (left/right common carotid velocity ratio) between sham and TAC mice (1.1 ± 0.1 vs 2.5 ± 0.5, p< 0.001) and this correlated well with a deteriorated left ventricular function in the TAC mice after 5 weeks. In this preclinical model of cardiac failure due to pressure overload with reduced LV ejection fraction in the mouse, the early increase in right carotid flow velocity (precoarctation) and especially the relationship between precoarctation/postcoarctation carotid flow velocities is associated with significant impairment of LV systolic function five weeks after the TAC, which allows to predict the effectiveness of the procedure in this experimental model.

Galectina-3: experiencia en pacientes chilenos con diagnóstico de insuficiencia cardíaca descompensada / Galectin-3 levels in patients hospitalized for decompensated heart failure

Background: Galectin-3 (Gal-3) is a mediator of myocardial fibrosis involved in cardiac remodeling and a potential new prognosis marker in heart failure (HF). Aim: To measure Gal-3 at the moment of discharge in patients hospitalized for HF and its association with different variables. Material and Methods: Patients hospitalized for decompensated HF from four hospitals between August 2014 and March 2015, were included. Demographic, clinical and laboratory variables were recorded at the time of admission. At discharge, a blood sample was withdrawn to measure Gal-3 and brain natriuretic propeptide (Pro-BNP). Patients were separated in two groups, according to the level of Gal-3 (using a cutoff value of 17.8 ng/mL), comparing clinical and laboratory values between groups. Results: We included 52 patients with HF aged 70 ± 17 years (42% females). Functional capacity was III-IV in 46% of patients and the ejection fraction was 34.9 ± 13.4%. Pro-BNP values at discharge were 5,323 ± 8,665 pg/mL. Gal-3 values were 23.8 ± 16.6 ng/mL. Sixty percent of patients had values over 17.8 ng/mL. Those with elevated Gal-3 levels were older (75 ±16 and 62 ± 15 years, respectively, p = 0.025) and were hypertensive in a higher proportion (90.5% and 57.1% respectively, p = 0.021). Conclusions: In patients hospitalized for HF, Gal-3 levels are higher in older and hypertensive subjects.

Factores asociados a fragilidad en pacientes hospitalizados con insuficiencia cardiaca descompensada / Frailty in patients admitted to hospital with acute decompensated heart failure

Background: Frailty is a geriatric syndrome characterized by a progressive impairment in the subjects’ ability to respond to environmental stress. Frailty is more commonly found in heart failure (HF) patients than in general population and it is an independent predictor of rehospitalization, emergency room visits and death. Aim: To estimate the prevalence of frailty in patients with decompensated HF admitted to four hospitals in Santiago, Chile. Material and Methods: Cross-sectional study. Subjects aged 60 or older consecutively admitted for decompensated HF to the study centers between August 2014 and March 2015 were included. Frailty was defined as the presence of three or more of the following criteria: unintended weight loss, muscular weakness, depression symptoms (exhaustion), reduced gait speed and low physical activity. Independent variables were tested for association using simple logistic regression. Variables associated with frailty (p < 0.05) were included in a multiple logistic regression model. Results: Seventy-nine subjects were included. The prevalence of frailty was 50.6%. Frail patients were mostly female (52.6%) and older than non-frail subjects (73.7± 7.9 vs 68.2 ± 7.1; p < 0.003). Independent predictors of frailty were age (Odds raio (OR) 1.10; 95% confidence intervals (CI): 1.03-1.17), quality of life measured with the Minnesota Living with Heart Failure Questionnaire (OR 1.07; IC95%: 1.03-1.11), previous hospitalizations (OR 2.56; 95%CI: 1.02-6.43) and number of medications (OR 4.46; 95%CI: 1.11-17.32). Conclusions: The prevalence of frailty in patients admitted to the hospital for decompensated heart failure is high. Age, quality of life, hospitalizations and polypharmacy were factors associated with frailty in this group of participants.

Sobrevida a mediano plazo en los pacientes con hipertensión arterial pulmonar en la era de terapias vasodilatadoras específicas del territorio vascular pulmonar / Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary vasodilator therapies

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy. Aim: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile. Patients and Methods: One hundred fifteen patients aged 43 ± 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 ± 14 mmHg and their six minutes walking capacity was 368 ± 119 m. They were followed for 58 ± 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH. Results: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival. Conclusions: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature.

Remodelado auricular derecho y niveles plasmáticos de galectina-3 se relacionan con la capacidad funcional de pacientes con hipertensión arterial pulmonar / Right atrial remodeling and plasma leves of galectin-3 are related to functional capacity in patiensts with pulmonary artery hypertension

Introducción: En pacientes con hipertensión arterial pulmonar (HAP) Galectina- 3, biomarcador de fibrosis miocárdica, se ha asociado a marcadores ecocardiográficos de remodelado ventricular derecho. La relación entre Galectina- 3, remodelado auricular derecho (AD) y capacidad funcional (CF) en pacientes con HAP no ha sido explorado. El objetivo fue medir niveles de Galectina-3 y su relación con CF y remodelado AD en pacientes con HAP Metodos: Estudio prospectivo observacional en que se incluyeron 14 pacientes con HAP En todos los pacientes se midieron los niveles de Galectina-3, proBNP, se evaluó la CF mediante test de caminata 6 minutos (TC6M) y se evaluó remodelado AD. Se consideraron para el análisis dos grupos según la distancia caminada en TC6M (> 200 m vs. ≤ 200 m). Resultados: La edad promedio fue 43 ± 10 años, el 84% mujeres. Los niveles de Galectina-3 fueron 16,1 ± 7,4 ng/mL y el TC6M fue 371 ± 142 mts. Los pacientes con TC6M< 200 m presentaron mayores niveles de Galectina-3 (27,3 ± 4,6 vs 13,7 ± 3,8; p=0,006) y mayor volumen AD (151 ± 21 vs 94 ± 43; p=0,04). Además, se observó una correlación inversa entre el área AD y TC6M (-0,71; p=0,03). Conclusión: Niveles elevados de Galectina-3 y parámetros de remodelado adverso en AD se relacionan con una menor CF en pacientes con HAP. Estos hallazgos apuntan a una mejor caracterización de pacientes con HAP y eventualmente la búsqueda de nuevos objetivos terapéuticos.

Background: Galectin-3 is a biomarker of myo-cardial fibrosis and has been associated with echocar-diographic markers of right ventricular remodeling in patients with pulmonary artery hypertension (PAH). The association among Galectin-3 level, right atrial (RA) remodeling and functional capacity (FC) has not been explored. The objective was to measure plasma Galectin-3 concentrations and its relation with RA remodeling and FC in PAH patients. Methods: This is a prospective observational study and 14 PAH patients were included. Galectin-3 and proBNP levels were measured in all patients. FC was estimated by the 6-minute walk test (6MWT) and used to define 2 groups of subjects (≤200m or >200m). RA area and volume were measured by echocardiography from a 4 chamber view. Results: The average age was 43±10 years, 84% of patients were female. Galectin-3 levels were 16.1±7.4 ng / mL and 6MWT was 371±142 m. We observed an inverse correlation between RA area and 6MWT (-0.71;p=0.03). Conclusions: Higher Galectin-3 concentrations and RA adverse remodeling are related to a decreased FC in PAH patients. These findings may lead to a better characterization of PAH patients and eventually new therapeutic targets.

Estimación indirecta de la función renal y mortalidad por insuficiencia cardíaca: buscando el mejor predictor / Estimation of renal function and mortality in congestive heart failure: a search for the best indicator

Antecedentes: Uno de los principales predictores de eventos adversos en pacientes con insuficiencia cardíaca (IC) es el deterioro de función renal luego de una hospitalización. Estudios recientes han cuestionado la utilidad de la fórmula de Cockroft-Gault (CG) para estimar la función renal en estos pacientes. Objetivo: Evaluar la utilidad de distintos modelos para determinación indirecta de función renal como pre-dictores de mortalidad alejada en sujetos con IC. Método: Estudio descriptivo analítico. Se incorporaron en forma consecutiva pacientes admitidos de 14 hospitales chilenos con el diagnóstico de IC descompensada entre enero 2002 y julio 2012. Las características de los pacientes se compararon mediante t de Student o chi cuadrado según correspondía. En base a la creatininemia al alta se estimó la tasa de filtración glomerular mediante las formulas CG, MDRD-4 y CKD-Epi. El acuerdo entre los resultados de cada fórmula se analizó mediante kappa de acuerdo para clasificación en estadios de función renal y según el método de Bland-Alt-man. Los pacientes se clasificaron por cuartiles según la estimación de cada fórmula; la sobrevida se analizó con el método de Kaplan-Meier y la capacidad de cada fórmula para predecir eventos mediante un modelo de riesgo proporcional de Cox. La mortalidad al fin del seguimiento se determinó por la base de datos del Servicio Nacional de Registro Civil e Identificación. Resultados: Se incluyeron 1584 pacientes, 45,3 por ciento de sexo femenino. La edad promedio fue de 70,5+/-20 años. La creatinina al ingreso fue 1,63+/-1,48 mg/dL y al egreso de 1,59+/-1,41 mg/dL (p=NS). Todos los modelos estimaron un porcentaje similar de población con falla renal al momento del alta (Cl Crea < 60 ml/min/1.73m2): CG 57,3 por ciento, MDRD-4 54,9 por ciento y CKD-Epi 54,9 por ciento. El clearance de creatinina estimado por CG (59,4+/-30,4 mL/min/1,74) fue mayor al estimado por CKD-Epi o MDRD-4 (54,2+/-25,1 y 57,8+/-27 mL/min/1,73m2)...

Background. One of the best predictors of adverse events in patients with congestive heart failure (CHF) is the deterioration of renal function following hospitalization. Recent studies have questioned the usefulness of the Cockroft-Gault (CG) formula to estimate renal function in these patients. Aim: To evaluate the usefulness of different indirect methods for estimation of renal function in the prediction of late mortality in patients with CHF. Method: Consecutive patients admitted for CHF in 14 different hospitals from January 2002 and July 2012 were analyzed. Student’s t or Chi square were used as appropriate for statistical comparisons. The serum creatinine level at the time of discharge was used to estimate glomerular filtration rate (GFR) from 3 different formulae: CG, MDRD-4 and CKD-Epi. Agreement among methods for different assignment to different stages of renal failure was evaluated by the "kappa" statistics and the Bland- Altmann method. Survival according to the estimation from each formula was compared by the log-rank statistics on Kaplan-Meier’s survival curves. The ability of each formula to predict adverse events was evaluated by a Cox proportional hazards method. Mortality was obtained from de National Identification Registry. Results: 1548 patients were included, 45.3 percent of them females. Mean age was 70.5 years (SD 20). Creatinine level was 1,63+/-1,48 mg/dL at admission and 1,59+/-1,41 mg/dL at discharge (p=NS). The proportion of patients with renal failure ( creatinine clearance < 60ml/min/1.73 m2) was similar for all methods (CG: 57.3 percent, MDRD-4 54.9 percent and CKD-Epi 54.9 percent). Creatinine clearance by CG (59,4+/-30,4 mL/min/1,73m2) was higher than that estimated by CKD-EPI (54,2+/-25,1/1.73 m2) or MDRD-4 (57,8+/-27 mL/min/1,73m2). Both CKD-Epi and MDMD-4 correctly identified a subgroup of patients with lower late mortality (CKD-Epi quartiles 3 and 4, OR 0,5 IC95 percent 0,35-0,72; MDRD-4 quartiles 3 and 4...

Rotura espontánea de válvula tricúspide en un paciente con hipertensión pulmonar secundaria a VIH / Spontaneous rupture of tricuspid valve papillary muscle in pulmonary hypertension secondary to HIV infection.Report of one case

Acute primary tricuspid regurgitation (TR) secondary to papillary muscle rupture is an extremely rare clinical situation. We report a 42-year-old male with pulmonary artery hypertension (PAH) secondary to HIV infection, who presented with an acute TR due to spontaneous papillary muscle rupture. He remained in cardiogenic shock despite therapy with inotropic drugs and pulmonary vasodilator therapy. He was subjected to a tricuspid valve replacement. In the postoperative period the patient had severe PAH, which was successfully controlled with inhaled nitric oxide. Tricuspid valve replacement and adjunctive use of pulmonary vasodilator therapy can be a life saving and useful approach in this condition.

Incidencia e importancia pronóstica del deterioro de la función renal en pacientes hospitalizados con insuficiencia cardiaca / Deterioration of kidney function as a risk factor for mortality among patients hospitalized for heart failure

Background: Acute deterioration of kidney function among patients admitted to the hospital for cardiac failure is associated with an increased mortality. Aim: To investigate the association between deterioration of kidney function and mortality among patients hospitalized for cardiac failure. Material and Methods: Patients admitted for decompensated cardiac failure to 14 Chilean hospitals between 2002 and 2009 were incorporated to the study. Clinical and laboratory features were registered. Serum creatinine values on admission and discharge were determined. Hospital and long term mortality was determined requesting death certificates to the National Identification Service at the end of follow up, lasting 635 ± 581 days. Results: One thousand sixty four patients were incorporated and 1100, aged 68 ± 13 years (45% females) had information about renal function. Seventy seven percent were hypertensive and 36% were diabetic. Mean ejection fraction was 41 ± 18% and 34% had an ejection fraction over 50%. Mean admission creatinine was 1.7 ± 1.6 mg/dl and 19% had a creatinine over 2 mg/dl. Serum creatinine increased more than 0.5 mg/dl during hospitalization in 9% of general patients and in 11% of diabetics. The increase in creatinine was associated with a higher risk of hospital mortality (odds ratio (OR) 12.9, 95% confidence intervals (CI) 6.7-27.6) and long term mortality (OR 2.1, 95% CI 1.6-3). Conclusions: The deterioration of renal function during hospitalization of patients with heart failure is a risk factor for hospital and long term mortality.

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.

Asociación entre strain y strain rate auricular izquierdo evaluado por speckle tracking y fibrilación auricular post cirugía de revascularización miocárdica / Speckle tracking derived left atrial strain and strain rate in patients with post myocardial revascularization atrial fibrillation

Introducción: La fibrilación auricular (FA) es la arritmia más común post cirugía de revascularización miocárdica (CRM) y está asociada a dilatación y disfunción auricular izquierda (AI). El strain y strain rate global longitudinal AI determinado por speckle tracking constituyen herramientas novedosas en la evaluación de la función AI. Objetivo: evaluar el strain y strain rate global longitudinal AI en pacientes con enfermedad coronaria con indicación de CRM y su relación con el desarrollo de FA post operatoria. Métodos: se incluyeron pacientes consecutivos con indicación de CRM, en ritmo sinusal con fracción de eyección > 50 por ciento. Se registraron características clínicas y ecocardiográficas con evaluación del strain AI: onda s (LASs) y strain rate: onda a (LASRa), onda s (LASRs) por speckle tracking (pre-cirugía). Se evaluó la ocurrencia de FA en el período post operatorio (una semana) mediante monitorización electrocardiografía continua. Se utilizó t-Student, chi-cuadrado y regresión logística múltiple. Resultados: Se incluyeron 70 pacientes, 26 por ciento presentaron FA. LASs, LASRr y LASRa estaban significativamente disminuidos en los pacientes que desarrollaron FA post CRM, LASs (10 +/- 1,1 vs 24 +/- 1,2 por ciento, p < 0,001), LASRa (- 0,6 +/- 0,1 vs - 1,8 +/- 0,12, p < 0,001) LASRs (0,6 +/- 0,007 vs 1,2 +/- 0,008, p < 0,001). Los pre-dictores independientes de FA fueron: LASRs OR: 6,1 IC 95 por ciento (1,3-15,2); LASRa OR: 2,4 IC 95 por ciento (1,1-19,6); volumen AI OR: 4,67 IC 95 por ciento (1,5-19,2) y edad > 65 años OR: 2,31 IC 95 por ciento (1,1-15,8). Conclusiones: LASs, LASRs y LASRa están disminudos en pacientes que desarrollan FA post CRM y LASRs, LASRa fueron predictores independientes de ésta.

Background: Atrial fibrillation (AF) is the commonest arrhythmia post coronary artery bypass grafting (CABG); it is associated to left atrial (LA) dilatation and dysfunction. Speckle tracking derived longitudinal strain and strain rate are novel techniques to evaluate LA function. Aim: to evaluate the relation of global longitudinal LA strain and strain rate with the development of AF in patients undergoing CABG. Methods: Consecutive patients undergoing CABG with LV ejection > 50 percent and sinus rhythm were included. Clinical characteristics were tabulated and LA echocar-diographic speckle tracking measurements, LASs, LAS-Ra, LARs, were used to determine LA strain and LA strain rate. Continuous ECG monitoring for 1 week was performed to assess the occurrence of AF. Student's t, chi square and multiple logistic regression were used for statistical analysis. Results. 70 patients were studied; 26 percent developed post-operative AF. Compared to patients remaining in sinus rhythm, patients developing post-operative AF had lower LASs (10 +/- 1,1 vs 24 +/- 1,2 percent, p < 0,001), LASRa (- 0,6 +/- 0,1 vs - 1,8 +/- 0,12, p < 0,001) and LASRs (0.6 +/- 0.007 vs 1.2 +/- 0.008, p < 0,001). Independent predictors of AF were LASRs (OR: 6.1, 95 percent CI 1.3-15.2); LASRa (OR: 2.4, 95 percent CI 1.1-19.6); LA volume (OR: 4,67, 95 percent CI 1.5-19.2) and age>65 years (OR: 2.31, 95 percent CI 1.1-15.8). Conclusion.: LASs , LASRs and LASRa are lower in patients who develop AF after CABG and LASRs and LASRa were independent predictors of post-operative AF. Thus, LA strain rate assessed by speckle tracking is useful for predicting AF after CABG in addition to classic risk factors such as age and LA volume.

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.

Estimación auscultatoria de la presiónsistólica de arteria pulmonar: ¿Es factible?. Correlación con determinación ecocardiográfica / Heart auscultatory assessment of pulmonary artery systolic pressure

The clinical assessment of pulmonary artery systolic pressure (PASP) by means of heart auscultation may be comparable to the measures obtained by Doppler echocardiography. Aim: To compare PASP estimated by heart auscultation and echocardiography. Material and Methods: Thirty consecutive patients aged 70 ± 16 years (68 percent women) were evaluated prospectively, all of whom had an echocardiogram requested by their attending physician. Echocardiographic evaluation of PASP was made by tricuspid regurgitation velocity plus right a trial pressure estimate. Two trained clinicians, blinded for the clinical history and rest of physical examination, auscultated the patients. PASP was estimated from the auscultatory intensity of the pulmonary component in comparison to the aortic component of the second heart sound and its propagation towards the apex, in accordance to a pre-established algorithm. Correlation between auscultatory and echocardiographic measures of PASP was made by Pearson test. Variability between both methods and among observers was evaluated with Bland-Altman analysis. Results: Fifty two per cent of patients were hypertensive and 20 percent diabetic. Admission diagnoses were heart failure in 50 percent of cases, exacerbation of chronic obstructive pulmonary disease in 20 percent, pulmonary thromboembolism in 10 percent and other clinical entities in 20 percent. A significant correlation was found between auscultatory and echocardiographic estimation of PASP (r = 0.64, p = 0, 01). Bland-Altman analysis showed a mean difference between both determinations of 7.6 ± 7.6 mmHg. Bland-Altman analysis between both operators showed an average difference of 5.4 ± 8.4 mm Hg. Conclusions: Heart auscultatory evaluation allows a precise and reproducible estimation of PASP and compares favorably with echocardiographic assessment.

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...

Polución por material particulado fino (PM 2.5) incrementa las hospitalizaciones por insuficiencia cardiaca / Small particle air pollution (PM2.5) leads to an in crease in hospitalization rate for congestive heart failure

Antecedentes: Estudios recientes han reportado una asociación entre la contaminación ambiental por material particulado (PM) y el riesgo de hospitalizaciones de pacientes con insuficiencia cardiaca (IC). La región metropolitana de nuestro país constituye un área geográfica en la cual la contaminación es especialmente relevante, asociándose a incrementos periódicos en la morbimortalidad por causa respiratoria. Sin embargo el efecto de la polución por PM en la morbilidad de pacientes con IC no ha sido evaluado en forma sistemática. Objetivo: Evaluar la asociación entre el PM fino y las hospitalizaciones por IC descompensada en hospitales pertenecientes al registro ICARO del área metropolitana. Métodos: Estudio prospectivo. Entre enero 2002 a diciembre de 2008 se recolectaron las fichas médicas de 529 pacientes residentes de Santiago hospitalizados por IC descompensada. Las variables meteorológicas y de contaminación fueron obtenidas de la red MACAM. Para estudiar la asociación entre las hospitalizaciones y los niveles de contaminación (PM10 y PM2,5), se aplicó un diseño de Casos cruzados estratificado por tiempo (Time-stratified Case-crossover), controlando por temperatura y punto de rocío. El impacto de los niveles de contaminación en el número de hospitalizaciones se evaluó asumiendo una latencia en el efecto de la polución de 0 a 10 días. Resultados: La edad media de la población en estudio fue de 73.8 años. La etiología más frecuente fue isquémica (27 por ciento) e hipertensiva (27 por ciento). Un 73.2 por ciento de los pacientes eran hipertensos y 32.6 por ciento tenían antecedentes de diabetes mellitus. Se observó un aumento en la admisión por IC descompensada en pacientes de ambos sexos, menores de 74 años, con desde un 22.7 por ciento (p=0.03) por cada incremento en 10 ug/m3 de PM2.5 calculado con media móvil, cuatro días después de la exposición hasta un 44.8 por ciento (p=0.006) a 10 días de la exposición. Los pacientes con antecedentes de ...

Background: Recent studies have reported an increase risk of hospitalization in patients with congestive heart failure (CHF) in association with air pollution by small particles. The Metropolitan region in Chile is characterized by high pollution indexes which are related to increased mortality from respiratory diseases. No systematic evaluation of the effect of particle pollution upon morbidity in patients with CHF is available. Aim. To evaluate the association between fine particle pollution and hospitalization rate for decompensated CHF in hospitals participating in the ICARO registry of CHF in the Metropolitan area of Santiago. Methods. In a prospective design the clinical records of 529 patients who were hospitalized for decompensated CHF from Jan 2002 to Dec 2008 were analyzed Meteorological and pollution indexes were obtained from de MACAM monitoring network. A time stratified case cross-over design was used to study the association between hospitalization rate and pollution indexes (PM10 and PM25. Data was controlled for temperature and "punto de rocío" . A 0 to 10 day latency period was estimated to evaluate the influence of pollution on hospitalization rate. Results. The mean age of patients was 73.8 years. Etiologies for CHF included ischemic heart disease (27 percent) and hypertensive heart disease (27 percent). 73.2 percent of patients were hypertensives and 32.6 percent had evidence of DM. Hospitalization rate for CHF in men or women > 74 years of age increased from 22.7 percent 4 days after exposure to 44.8 percent 10 days after exposure (p=0.006). Diabetic patients were more susceptible to hospitalization with an 18 percent increased rate for each 10ug/m3 PM2.5 concentration at 8 days after exposure. Male and female hypertensive patients <74 years of age were also susceptible with a 28 percent (2.1 to 43/5 percent, CI) increase in hospitalization rate at 5 days after exposure. Conclusion: Patients with CHF who are diabetics or hy...

La disincronía cardíaca se correlaciona con el remodelado ventrícular izquierdo postinfarto agudo al miocardio / Cardiac dyssynchrony correlates with left ventricular remodeling after myocardial Infarction

Background: Cardiac dyssynchrony is common in advanced heart failure (HF), but the changes in cardiac synchrony after myocardial infarction (MI) have not been adequately descríbed. Aim: To study the relationship between cardiac synchrony and left ventricular remodeling after acute myocardial infarction. Material and methods: Forty nine patients aged 59±10 years (77 percent men) with a first episode of a ST segment elevation MI, were studied. Scintigraphic left ventricular function and synchrony analyses were performed at baseline and after a six months follow-up. Determinations were compared with 33 healthy subjects. Results: At baseline, patients with MIhad a decreased left ventricular ejection fraction (LVEF) and significant dyssynchrony, when compared with controls. LVEF was 36.4 percent±10 percent, left ventricular end-diastolic volume (LVEDV) 127±38 mL, interventricular delay (IEV) 29±35 miliseconds (ms), and intraventricular delay (IAV), 234±89 ms. After 6 months, LVEF significantly improved (38 percent±10 percent, p =0.042) without significant changes in LVEDV (129±32 mL, p =0.97), IEV (24±17, p =0.96) or IAV (231±97, p =0.34). At baseline there were significant correlations between IAV and LVEF, and between IAV and LVEDV (r =0.48, p =0.001 and r =0.41, p =0.004, respectively). These correlations remained significant after 6 months. There was a positive correlation between IAV and LVEDV changes at six months (r =0.403, p =0.04). Conclusions: The development of cardiac dyssynchrony correlates with adverse left ventricular remodeling after MI.

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.