Insuficiencia cardíaca crónica en Argentina. OFFICE IC AR, un registro conjunto de la Sociedad Argentina de Cardiología y de la Federación Argentina de Cardiología / Chronic Heart Failure in Argentina. OFFICE IC AR, a joint registry of the Argentine Society of Cardiology and the Argentine Federation of Cardiology

RESUMEN Introducción: Diferentes registros argentinos de insuficiencia cardíaca crónica (ICC) fueron generados en los últimos 25 años, en forma individual por la Sociedad Argentina de Cardiología (SAC) y la Federación Argentina de Cardiología (FAC), con diversa representatividad. Los últimos datos conocidos datan de 2013. El Registro OFFICE IC AR fue encarado en forma conjunta por la SAC y la FAC para conocer la realidad de la ICC en Argentina. Objetivos: Describir en forma amplia y comprensiva las características salientes de la ICC en Argentina, incluyendo las características de los pacientes, el uso de recursos diagnósticos y terapéuticos, la adherencia a las guías de práctica y el pronóstico a mediano y largo plazo. Material y Métodos: Estudio prospectivo de cohorte, de pacientes con ICC de al menos 6 meses de evolución, alejados de una internación por al menos 3 meses. Se recabaron datos clínicos y paraclínicos. Los pacientes fueron categorizados, de acuerdo a la fracción de eyección ventricular izquierda (FEVI), en IC con FE reducida, ICFER (≤40%); IC con FE en el rango medio, ICFErm, ahora denominada IC con FE levemente reducida, ICFElr (41%-49%), e IC con FE preservada, ICFEP (≥50%). En seguimiento de al menos 1 año se registró la incidencia de hospitalización por insuficiencia cardíaca (HIC), muerte cardiovascular (MCV) y muerte de todas las causas (MTC) Resultados: Entre noviembre de 2017 y enero de 2020, 100 cardiólogos de todo el país incluyeron 1004 pacientes con ICC; edad media 65,8 ± 12,4 años, 74,6% hombres, FEVI conocida en el 93,8%. El 68,4% tenía ICFER, el 16% ICFElr y el 15,6% ICFEP. Hubo alta prevalencia de comorbilidades, incluyendo diabetes y anemia en el 30%, e insuficiencia renal crónica en el 22%. Fue elevada la utilización de antagonistas neurohormonales (ANH): 89,5% betabloqueantes; 57,3% inhibidores o antagonistas del sistema renina angiotensina, 28,9% sacubitril valsartán y 78,6% antialdosterónicos. En 69% se utilizó triple terapia. Su empleo fue mayor en la ICFER, pero elevado incluso en la ICFEP. En una mediana de seguimiento de 1,7 años la incidencia anual de MCV/HIC fue 12,8%, la de MCV 6,6% y la de MTC 8,4%, sin diferencia entre las distintas categorías de FEVI. Conclusiones: En el primer registro conjunto de ICC SAC-FAC se verificó elevada prevalencia de ICFER, alta prevalencia de comorbilidades, uso frecuente de ANH y pronóstico acorde a los registros internacionales.

ABSTRACT Background: Several Argentine registries on chronic heart failure (CHF) have been generated over the past 25 years, either individually by the Argentine Society of Cardiology (SAC) or the Argentine Federation of Cardiology (FAC), with different representativeness. The last known data are from 2013. The OFFICE IC AR registry was jointly undertaken by the SAC and FAC to know the reality of CHF in Argentina. Objective: The aim of this registry was to extensively and comprehensively describe the outstanding characteristics of CHF in Argentina, including patient characteristics, use of diagnostic and therapeutic resources, adherence to practice guidelines and mid-and long-term prognosis. Methods: This was a prospective cohort study of patients with at least 6-month evolution CHF and not hospitalized for at least the past 3 months. Clinical and paraclinical data were collected. Patients were categorized according to left ventricular ejection fraction (LVEF), into HF with reduced EF, HFrEF (≤40 %), HF with midrange EF, now termed HF with mildly reduced EF, HFmrEF (41%-49%), and HF with preserved EF, HFpEF (≥50%). The incidence of hospitalization for HF (HHF), cardiovascular mortality (CVM) and all-cause mortality (ACM) was recorded for at least 1-year follow-up. Results: Between November 2017 and January 2020, 100 cardiologists from all over the country included 1004 patients with CHF. Mean age was 65.8 ± 12.4 years, 74.6% were men, and 93.8% had known LVEF. In 68.4% of cases, patients had HFrEF, 16% HFmrEF and 15.6% HFpEF. A high prevalence of comorbidities was found, including diabetes and anemia in 30% of cases, and chronic renal failure in 22%. There was high use of neurohormonal antagonists (NHA): 89.5% betablockers, 57.3% renin-angiotensin system inhibitors or antagonists, 28.9% sacubitril-valsartan and 78.6% aldosterone antagonists. Triple therapy was used in 69% of patients, with higher prescription in HFrEF, but elevated even on HFpEF. At a median follow-up of 1.7 years, the annual incidence of CVM/HHF was 12.8%, CVM 6.6% and ACM 8.4%, without statistical differences between the different LVEF categories. Conclusions: This first SAC-FAC joint CHF registry verified a high prevalence of HFrEF, a high prevalence of comorbidities, frequent use of NHA and prognosis according to international registries.

Prevalence, evolution, and related risk factors of kidney disease among Spanish HIV-infected individuals.

Prevalence of kidney disease (KD) is increasing among human immunodeficiency virus (HIV)-infected population. Different factors have been related, varying on different published series.The objectives were to study prevalence of KD in those patients, its evolution, and associated risk factors.An observational cohort study of 1596 HIV-positive patients with cross-sectional data collection in 2008 and 2010 was conducted. We obtained clinical and laboratory markers, and registered previous or current treatment with tenofovir (TDF) and indinavir (IDV). The sample was divided according to estimated glomerular filtration rate (eGFR) by modification of diet in renal disease (MDRD) equation. Group 1: eGFR ≤60 mL/min/1.73 m; group 2: eGFR >60 mL/min/1.73 m.Among the patients, 76.4% were men, mean age (SD) 45 ±â€Š9 years, time since diagnose of HIV 14 ±â€Š7 years, and 47.2% of the patients received previous treatment with TDF and 39.1% with IDV. In 2008, eGFR ≤60: 4.9% (91.4% of them in chronic kidney disease [CKD] stage 3, eGFR 59-30 mL/min); this group was older, presented higher fibrinogen levels, and more patients were treated previously with TDF and IDV. In 2010, eGFR ≤60: 3.9% (87.1% stage 3 CKD). The 2.4% of cohort showed renal improvement and 1.3% decline of renal function over time. The absence of hypertension and treatment with TDF were associated with improvement in eGFR. Increased age, elevated fibrinogen, decreased albumin, diabetes mellitus, hyperTG, and worse virological control were risk factors for renal impairment.The HIV-positive patients in our area have a CKD prevalence of 4% to 5% (90% stage 3 CKD) associated with ageing, inflammation, worse immune control of HIV, TDF treatment, and metabolic syndrome.

Three-component solids velocity measurements in the outlet section of a riser.

Coincident (simultaneous) three-component particle velocity measurements performed using two laser Doppler anemometry probes at the outlet section of a 9 m high cylindrical riser are for the first time presented for dilute flow conditions. Near the blinded extension of the T-outlet a solids vortex is formed. Particle downflow along the riser wall opposite the outlet tube is observed, which is restricted to higher riser heights at higher gas flow rates. Increased velocity fluctuations are observed in the solids vortex and downflow region as well as at heights corresponding to the outlet tube. Contrary to the rest of the riser, in the downflow region time and ensemble velocity averages are not equal. Given the local bending of the streamlines, axial momentum transforms to radial and azimuthal momentum giving rise to the corresponding shear stresses. Turbulence intensity values indicate the edges of the downflow region.

Evaluation of protease inhibitors containing tubes for MS-based plasma peptide profiling studies.

BACKGROUND: Peptide profiling of biological fluids is a promising tool for biomarker discovery. Blood is an ideal entity for proteomic studies but it is subjected to a proteolytic activity that sets up just at the moment of phlebotomy. Intending to prevent this proteolytic activity, tubes containing protease inhibitors (PI) have been developed. In this study, we evaluated the effect on plasma peptide profile of using tubes containing PI and the evolution of this effect over time. METHODS: Blood samples from ten subjects were drawn into conventional tubes containing ethylenediaminetetraacetic acid (EDTA) and tubes containing PI. Samples were processed at time "zero" and after 1, 2, 4, and 8 hr. Plasma peptide profiles were analyzed by magnetic bead based technology coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry readout. RESULTS: When comparing plasma peptide profile of blood samples collected into tubes containing PI with samples collected into conventional EDTA tubes, differences in the area of 13 peaks were detected at time "zero"; after 8 hr these differences tended to disappear. Moreover, bradykinin and C3- and C4-derived peptides were produced promptly after blood extraction when samples were collected into conventional EDTA tubes, and the use of PI prevented their generation. CONCLUSION: Considering that time taken to process blood samples affects their peptide profile and a decrease in PI's effect occurs over time, it may be concluded that the use of tubes containing PI for blood collection may be advantageous in the context of research, but may have some limitations regarding clinical practice.

Predictores ecocardiográficos de capacidad de ejercicio en pacientes con insuficiencia cardiaca sistólica. Valor de la insuficiencia mitral / Echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction: role of mitral regurgitation

Introducción y objetivos. Pacientes con insuficiencia cardiaca y similar disfunción sistólica del ventrículo izquierdo tienen diferente capacidad de ejercicio. El objetivo de este estudio es detectar predictores ecocardiográficos de capacidad de ejercicio en pacientes con insuficiencia cardiaca y disfunción sistólica. Métodos. Se incluyó a 150 pacientes con insuficiencia cardiaca en clase II (70%) o III (30%) con fracción de eyección ventricular izquierda < 40%. Se efectuó prueba de los 6 minutos de marcha y eco-Doppler color cardiaca, incluyendo Doppler tisular de los anillos mitral y tricuspídeo. Se consideró insuficiencia mitral significativa los grados moderado y severo. Se dividió a los pacientes en dos grupos según la mediana de caminata (290 m): el grupo 1 caminó <290 m y el grupo 2, >=290 m. Resultados. Se detectó insuficiencia mitral en 112 pacientes (75%), que fue significativa en 40 (27%). El grupo 1 evidenció más insuficiencia mitral significativa (el 35 frente al 18%), área auricular izquierda (27±1 frente a 24±1cm2), amplitud de E mitral (88±5 frente a 72±3cm/s) y presión sistólica pulmonar (37±1 frente a 32±1 mmHg; todos p<0,05). En el análisis multivariable de regresión logística, sólo la presencia de insuficiencia mitral significativa se asoció en forma independiente a menor distancia caminada (odds ratio=3,44; intervalo de confianza del 95%, 1,02-11,66; p<0,05). En el análisis de regresión lineal múltiple, el único predictor independiente de la distancia caminada fue el área auricular izquierda (r=0,25; Beta=–6,52±2; p<0,01). Conclusiones. En pacientes con insuficiencia cardiaca en clase II-III y disfunción sistólica ventricular izquierda, los principales predictores ecocardiográficos de capacidad de ejercicio se relacionan con la presencia de insuficiencia mitral significativa (AU)

Introduction and objectives. Patients with heart failure and similar left ventricular systolic dysfunction have differing exercise capacity. The aim of this study was to identify echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction. Methods. We included 150 patients with class II (70%) or III (30%) heart failure with left ventricular ejection fraction below 40%. Six-minute walking test and cardiac color Doppler-echo, including tissue Doppler of mitral and tricuspid rings, were performed. Moderate and severe mitral regurgitation were considered as significant. Two groups were divided according to the median walking distance (290 m): Group 1, < 290 m and Group 2, >=290 m. Results. Mitral regurgitation was detected in 112 patients (75%), which was significant in 40 (27%). Group 1 showed more significant mitral regurgitation (35 vs 18%), increased left atrium area (27±1 vs 24±1cm2), mitral E amplitude (88±5 vs 72±3cm/s) and systolic pulmonary pressure (37±1 vs 32±1mmHg, all P<.05). By logistic regression analysis, only the presence of significant mitral regurgitation was independently associated with less walked distance (odds ratio: 3.44 95% confidence interval 1.02-11.66, P<.05). By multiple linear regression, the only independent predictor of walked distance was left atrium area (r=0.25, beta coefficient: −6.52±2, P<.01). Conclusions. In patients with class II-III heart failure and left ventricular systolic dysfunction, the main echocardiographic predictors of exercise capacity are related to the presence of significant mitral regurgitation (AU)

[Echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction: role of mitral regurgitation]. / Predictores ecocardiográficos de capacidad de ejercicio en pacientes con insuficiencia cardiaca sistólica. Valor de la insuficiencia mitral.

INTRODUCTION AND OBJECTIVES: Patients with heart failure and similar left ventricular systolic dysfunction have differing exercise capacity. The aim of this study was to identify echocardiographic predictors of exercise capacity in patients with heart failure and systolic dysfunction. METHODS: We included 150 patients with class II (70%) or III (30%) heart failure with left ventricular ejection fraction below 40%. Six-minute walking test and cardiac color Doppler-echo, including tissue Doppler of mitral and tricuspid rings, were performed. Moderate and severe mitral regurgitation were considered as significant. Two groups were divided according to the median walking distance (290 m): Group 1, <290 m and Group 2, ≥290 m. RESULTS: Mitral regurgitation was detected in 112 patients (75%), which was significant in 40 (27%). Group 1 showed more significant mitral regurgitation (35 vs 18%), increased left atrium area (27±1 vs 24±1cm(2)), mitral E amplitude (88±5 vs 72±3cm/s) and systolic pulmonary pressure (37±1 vs 32±1mmHg, all P<.05). By logistic regression analysis, only the presence of significant mitral regurgitation was independently associated with less walked distance (odds ratio: 3.44 95% confidence interval 1.02-11.66, P<.05). By multiple linear regression, the only independent predictor of walked distance was left atrium area (r=0.25, beta coefficient: -6.52±2, P<.01). CONCLUSIONS: In patients with class II-III heart failure and left ventricular systolic dysfunction, the main echocardiographic predictors of exercise capacity are related to the presence of significant mitral regurgitation.

Relation of left ventricular ejection fraction and functional capacity with metabolism and inflammation in chronic heart failure with reduced ejection fraction (from the MIMICA Study).

Catabolism and inflammation play a role in the physiopathology of heart failure with reduced ejection fraction and are more pronounced in the advanced stages of the disease. Our aim was to demonstrate that in patients with stable heart failure with reduced ejection fraction adequately treated, a direct relation exists between functional impairment, as evaluated by left ventricular ejection fraction (LVEF) and the 6-minute walking distance (6MWD), and catabolic and inflammatory markers. In 151 outpatients with heart failure and a LVEF of < or =40% (median age 64 years, LVEF 29%, and 6MWD 290 m) we measured the laboratory and body composition parameters that indicate directly or indirectly inflammatory activation, anabolic-catabolic balance, and nutritional status. We performed an analysis stratified by quartiles of LVEF and 6MWD and linear regression analysis to explore our hypothesis. In the linear regression analysis, after adjusting for age, gender, and etiology, LVEF was not related to the metabolic, inflammatory, or nutritional parameters. The 6MWD was directly related to albumin (p = 0.002) and log transformation of dehydroepiandrosterone (p = 0.013) and inversely to adiponectin (p = 0.001) and the log-transformation of high-sensitivity C-reactive protein (p = 0.037). In conclusion, in a population with stable heart failure with reduced ejection fraction, the 6MWD was related to the degree of inflammatory activity and catabolism, but LVEF was not. Even a slightly diminished functional capacity implies underlying inflammation and catabolic activation.

Perfil clínico y funcional de los pacientes con insuficiencia cardíaca sistólica y disfunción renal / Clinical and Functional Profile of Patients with Systolic Heart Failure and Renal Dysfunction

Introducción La disfunción renal está fuertemente asociada con la insuficiencia cardíaca crónica. Es una complicación habitual y progresiva de esta condición, con una evolución clínica que fluctúa con la clase funcional y el tratamiento farmacológico. Objetivos Definir la prevalencia y el perfil clínico y funcional de pacientes con disfunción renal en el contexto de insuficiencia cardíaca con baja fracción de eyección. Material y métodos En 132 pacientes con insuficiencia cardíaca y fracción de eyección < 40% se midió la depuración de creatinina. Se definió disfunción renal a una depuración de creatinina < 60 ml/ min. Se realizaron analítica sanguínea, ecocardiograma, bioimpedanciometría y caminata de 6 minutos. Resultados La prevalencia de disfunción renal fue del 43,2% (57 pacientes). Comparados con el resto, en estos pacientes hubo mayor prevalencia de sexo femenino, mayor edad y menos frecuentemente etiología coronaria. En el laboratorio tuvieron valores menores de hemoglobina, albúmina, ferritina y triyodotironina y mayor prevalencia de troponina T dosable. Fueron menores el índice de masa corporal (IMC), la tasa metabólica basal, la masa muscular y el ángulo de fase, mientras que la relación agua extracelular/agua corporal total fue mayor. La distancia recorrida en la prueba de 6 minutos fue menor. Respecto del tratamiento, sólo difirió el uso de betabloqueantes y amiodarona. En el análisis multivariado, la edad, el nivel de NT-proBNP, la presencia de troponina T positiva y la masa muscular como variable continua fueron predictores independientes de disfunción renal en pacientes con insuficiencia cardíaca sistólica. Conclusiones La disfunción renal es frecuente en pacientes con insuficiencia cardíaca con baja fracción de eyección y se vincula con características distintivas que pueden contribuir a explicar el cuadro clínico.

Background Renal dysfunction is strongly associated with chronic heart failure, and is a frequent and progressive complication of this condition, with clinical outcomes which depend on the functional class and pharmacological treatment. Objectives To define the prevalence and the clinical and functional profile of patients with renal dysfunction in the setting of heart failure with depressed ejection fraction. Material and Methods Creatinine clearance was measured in 132 patients with heart failure and an ejection fraction <40%. Renal dysfunction was defined as a creatinine clearance <60 ml/min. Patients underwent routine lab tests, echocardiogram, bioelectrical impedance analysis and 6-minute walk test. Results The prevalence of renal dysfunction was 43.2% (57 patients). Among these patients, there was a greater prevalence of women and elder subjects, yet the prevalence of coronary artery disease was low. Lab tests showed lower levels of hemoglobin, albumin, ferritin and triiodothyronine, and greater prevalence of measurable levels of troponin T. Body mass index (BMI), basal metabolic rate, muscle mass and phase angle were lower, while the ratio of extracellular water to total body water was greater in patients with renal dysfunction. The distance walked in the 6-minute test was lower. The use of beta blockers and amiodarone was the only difference in therapy. At multivariate analysis, age, NTproBNP level, the presence of positive troponin T and muscle mass as a continuous variable were independent predictors of renal dysfunction in patients with systolic heart failure. Conclusions Renal dysfunction is frequent in patients with heart failure with depressed ejection fraction and is associated with distinctive features that may contribute to explain the clinical picture.

Evaluación de los niveles plasmáticos de células progenitoras en pacientes con enfermedad coronaria crónica / Assessment of Plasmatic Levels of Endothelial Progenitor Cells in Patients with Chronic Coronary Disease

Introducción El ejercicio físico es útil para los pacientes con enfermedad coronaria y es un estímulo para el desarrollo de circulación colateral. Ésta podría estar determinada por un aumento en la producción y circulación de células progenitoras. Objetivo Evaluar el efecto del ejercicio físico programado sobre la producción y el número circulante de células progenitoras en pacientes coronarios crónicos estables. Material y métodos Estudio prospectivo, controlado, aleatorizado y abierto con la inclusión de 18 pacientes (8 en grupo ejercicio y 10 en grupo control) con enfermedad coronaria estable, < 75 años, que no hubieran participado en grupos de ejercicio programado en los últimos 3 meses. La determinación de las células progenitoras se realizó por citometría de flujo utilizando marcaciones con anticuerpos monoclonales CD45-FITC, CD34-FITC y CD133/1-PE. Resultados En el grupo control, el nivel de CD45 no tuvo variación significativa (0,724 ± 0,256 versus 0,765 ± 0,216 [media ± EE cada 100.000 eventos]), mientras que en el grupo ejercicio el nivel de CD45(+)/CD133(+) se incrementó de 0,497 ± 0,161 a 2,265 ± 1,003 luego de un mes de actividad física programada sin alcanzar significación estadística. Al analizar los niveles de CD34 se observó que en el grupo control se incrementaron de 0,196 ± 0,086 a 0,235 ± 0,063 (p = NS). En el grupo ejercicio, la variación fue mucho mayor: 0,220 ± 0,078 a 0,844 ± 0,172 (p = 0,0046; p = 0,0092 versus el grupo control). Conclusión El ejercicio físico programado en pacientes coronarios promueve un incremento de las células progenitoras circulantes. Su estímulo persistente podría ser la base para un mayor desarrollo de circulación colateral.

Background Exercise is useful for patients with coronary artery disease, and it works as a stimulus for the development of collateral circulation, which could be the result of an increase in the production and circulation of endothelial progenitor cells. Objective The objective of this study was to assess the effect of programmed exercise on the production and number of circulating endothelial progenitor cells in patients with chronic and stable coronary disease. Material and Methods We conducted a prospective, randomized, controlled and open study that included 18 patients (8 in the exercise group and 10 in the control group) with demonstrated chronic stable angina, < 75 years. Patients eligible should not have participated in programmed exercise groups within the last 3 months. Progenitor cells were determined by flow cytometry using marked monoclonal antibodies CD45-FITC, CD34-FITC y CD133/1-PE. Results After 1 month of programmed physical activity, CD45 level did not show any significant change in the control group (0.724±0.256 vs 0.765±0.216 [mean ± SE each 100,000 events]), whereas it increased from basal levels of 0.497±0.161 to 2.265±1.003 in the exercise group, though this change was not statistically significant. Analyzing CD34 levels, an increase from 0.196±0.086 to 0.235±0.063 was seen in the control group (p = NS). This increase was greater in the exercise group: 0.220±0.078 to 0.844±0.172 (p=0.0046; p=0.0092 vs control group). Conclusions In patients with coronary artery disease, programmed exercise promotes an increase in the level of circulating progenitor cells. Its persistent stimulus could be the basis of a greater development of collateral circulation.

Gradual deregulation and loss of PCPH expression in the progression of human laryngeal neoplasia.

PCPH is a gene involved in the regulation of eukaryotic cell proliferation and stress response. Recently, analyses of human and animal solid tumors and cell lines suggested that PCPH protein deregulation may participate in neoplastic progression. To test this possibility, we first examined PCPH expression in several laryngeal carcinoma cell lines by Western analysis. The results showed the presence of altered PCPH polypeptides in these cells, accompanied by the loss of the PCPH form present in normal laryngeal epithelial cells, a deregulated expression pattern similar to that reported previously. We then analyzed PCPH expression in 59 dysplastic lesions of the human larynx, representative of the mild, moderate, and severe stages of the disease. Immunohistochemical data showed that, compared with normal laryngeal mucosa, PCPH expression in the dysplastic samples was associated with areas of epithelial cell maturation rather than with regions of increased proliferation. Furthermore, PCPH expression decreased parallel to the increase in cellular atypia of the dysplastic samples: PCPH either was expressed at very low levels or not expressed in cases of severe dysplasia/carcinoma in situ. This trend toward loss of PCPH expression along malignant progression of the larynx was confirmed by the low to null expression of PCPH in samples of invasive laryngeal carcinoma and by the complete absence of PCPH immunostaining in a laryngeal carcinoma-derived liver metastasis. These results indicated that PCPH protein analysis might allow for the distinction between grades of laryngeal dysplasia. In addition, detection of altered PCPH polypeptides by Western analysis potentially can be applied to the early identification of laryngeal squamous cell carcinoma.