Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Persistent Overactive Cytotoxic Immune Response in a Spanish Cohort of Individuals With Long-COVID: Identification of Diagnostic Biomarkers.

Long-COVID is a new emerging syndrome worldwide that is characterized by the persistence of unresolved signs and symptoms of COVID-19 more than 4 weeks after the infection and even after more than 12 weeks. The underlying mechanisms for Long-COVID are still undefined, but a sustained inflammatory response caused by the persistence of SARS-CoV-2 in organ and tissue sanctuaries or resemblance with an autoimmune disease are within the most considered hypotheses. In this study, we analyzed the usefulness of several demographic, clinical, and immunological parameters as diagnostic biomarkers of Long-COVID in one cohort of Spanish individuals who presented signs and symptoms of this syndrome after 49 weeks post-infection, in comparison with individuals who recovered completely in the first 12 weeks after the infection. We determined that individuals with Long-COVID showed significantly increased levels of functional memory cells with high antiviral cytotoxic activity such as CD8+ TEMRA cells, CD8±TCRγδ+ cells, and NK cells with CD56+CD57+NKG2C+ phenotype. The persistence of these long-lasting cytotoxic populations was supported by enhanced levels of CD4+ Tregs and the expression of the exhaustion marker PD-1 on the surface of CD3+ T lymphocytes. With the use of these immune parameters and significant clinical features such as lethargy, pleuritic chest pain, and dermatological injuries, as well as demographic factors such as female gender and O+ blood type, a Random Forest algorithm predicted the assignment of the participants in the Long-COVID group with 100% accuracy. The definition of the most accurate diagnostic biomarkers could be helpful to detect the development of Long-COVID and to improve the clinical management of these patients.

Impaired Cytotoxic Response in PBMCs From Patients With COVID-19 Admitted to the ICU: Biomarkers to Predict Disease Severity.

Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.

Identification of Immunological Parameters as Predictive Biomarkers of Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission.

BCR-ABL is an aberrant tyrosine kinase responsible for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKIs) induce a potent antileukemic response mostly based on the inhibition of BCR-ABL, but they also increase the activity of Natural Killer (NK) and CD8+ T cells. After several years, patients may interrupt treatment due to sustained, deep molecular response. By unknown reasons, half of the patients relapse during treatment interruption, whereas others maintain a potent control of the residual leukemic cells for several years. In this study, several immunological parameters related to sustained antileukemic control were analyzed. According to our results, the features more related to poor antileukemic control were as follows: low levels of cytotoxic cells such as NK, (Natural Killer T) NKT and CD8±TCRγß+ T cells; low expression of activating receptors on the surface of NK and NKT cells; impaired synthesis of proinflammatory cytokines or proteases from NK cells; and HLA-E*0103 homozygosis and KIR haplotype BX. A Random Forest algorithm predicted 90% of the accuracy for the classification of CML patients in groups of relapse or non-relapse according to these parameters. Consequently, these features may be useful as biomarkers predictive of CML relapse in patients that are candidates to initiate treatment discontinuation.

Congenital complete absence of pericardium in a young woman with non-specific symptoms.

Congenital absence of the pericardium is a very rare entity that is usually asymptomatic and hence difficult to diagnose. However, cases of sudden death have been reported in patients with partial pericardial defects (even asymptomatic ones), and such patients require surgical treatment. We report the case of a 17-year-old patient with complete pericardial agenesis (diagnosed by chance during a cardiological consultation) and briefly review the radiological findings of this entity.

Monitoring complex secundum atrial septal defects percutaneous closure with real time three-dimensional echocardiography.

BACKGROUND: Atrial septal defect (ASD) is one of the most common congenital heart diseases. Nowadays, percutaneous closure is considered the treatment of choice in most of secundum ASDs. Assessment of the defect and procedure monitoring have been usually performed by angiographic balloon-sizing and/or two-dimensional (2D) transesophageal echocardiography. However, in complex ASDs these techniques might be inaccurate. METHODS: From January 2009 to January 2011 all adult patients with complex ASDs submitted for percutaneous closure were selected. Those defects, where shunts were present through a device previously implanted on the atrial septum or through multiperforated septums, were considered complex ASDs. Two-dimensional transesophageal echocardiography and real time three-dimensional (3D) echocardiography were performed simultaneously during the percutaneous closure procedure. Number of orifices, relationships between the defect, catheter, and device, as well as residual shunt were assessed. RESULTS: Seven patients were included. Five patients had a multiperforated septum and in two cases the defect in the septum was through a previously implanted device. In all cases, 3D echocardiography was superior to 2D echocardiography in relation to the assessment of the relationship between the defect and the catheter or the device. Mechanisms responsible for residual shunts through a device were also better assessed by 3D echocardiography. CONCLUSION: Three-dimensional echocardiography is a safe and useful technique when monitoring percutaneous closure of ASDs, showing relevant advantages over 2D echocardiography.

Influencia de la desnutrición en la mortalidad a largo plazo de pacientes hospitalizados por insuficiencia cardiaca / Impact of malnutrition on long-term mortality in hospitalized patients with heart failure

Introducción y objetivos. Actualmente se desconoce la prevalencia de desnutrición entre los pacientes con insuficiencia cardiaca y el papel que este estado pudiera tener en su pronóstico. El objetivo de este estudio es analizar la prevalencia y riesgo de desnutrición y su posible influencia en la mortalidad a largo plazo de los pacientes con insuficiencia cardiaca. Métodos. Se analizó prospectivamente a 208 pacientes dados de alta consecutivamente desde nuestro centro entre enero de 2007 y marzo de 2008 tras un ingreso por insuficiencia cardiaca. Antes del alta, se realizó una completa valoración nutricional y se realizó el diagnóstico de desnutrición y riesgo de desnutrición mediante la encuesta Mini Nutritional Assessment. Su posible asociación independiente con la mortalidad se valoró mediante un análisis multivariable de Cox. Resultados. La media de edad fue 73±10 años, el 46% eran mujeres y la etiología más frecuente de la insuficiencia cardiaca fue la isquémica (41%). El 13% de los pacientes fueron clasificados como desnutridos; el 59,5%, en riesgo de desnutrición y el 27,5%, bien nutridos. A los 25 meses (mediana de seguimiento), la mortalidad en los tres grupos fue del 76, el 35,9 y el 18,9% respectivamente (log-rank test, p<0,001). En el análisis multivariable de Cox, el estado de desnutrición resultó ser un predictor independiente de mortalidad (hazard ratio=3,75; intervalo de confianza del 95%, 1,75-8,02; p=0,001). Conclusiones. La desnutrición y el de riesgo de desnutrición alcanzan una prevalencia elevada en pacientes hospitalizados por insuficiencia cardiaca. Además, hemos encontrado que el estado de desnutrición definido mediante el Mini Nutritional Assessment es un predictor independiente de mortalidad en estos pacientes (AU)

Introduction and objectives. The prevalence of malnutrition among patients with heart failure and the role it might play in prognosis is not currently known. The aim of this study was to analyse the prevalence and risk of malnutrition as well as its possible influence on long-term mortality in patients with heart failure. Methods. A prospective analysis was conducted on 208 patients discharged consecutively from our centre between January 2007 and March 2008 after being hospitalised with heart failure. Before discharge, a complete nutritional assessment was performed and diagnosis of malnutrition and risk of malnutrition was done with the Mini Nutritional Assessment. Its possible independent association with mortality was assessed by a Cox multivariate analysis. Results. The mean age of the patients was 73±10 years, with 46% women; the most common aetiology of heart failure was ischaemia (41%). In addition, 13% were classified as malnourished, 59.5% at risk of malnutrition and 27.5% were well-nourished. At a median follow-up of 25 months, mortality in the three groups was 76%, 35.9% and 18.9%, respectively (log-rank, P<.001). In the Cox multivariate analysis, the malnutrition state was an independent predictor of mortality (hazard ratio 3.75, 95% confidence interval, 1.75-8.02, P=.001). Conclusions. Malnutrition and the risk of malnutrition are highly prevalent in patients hospitalised for heart failure. Furthermore, we found that the state of malnutrition as defined by the Mini Nutritional Assessment survey is an independent predictor of mortality in these patients (AU)

[Impact of malnutrition on long-term mortality in hospitalized patients with heart failure]. / Influencia de la desnutrición en la mortalidad a largo plazo de pacientes hospitalizados por insuficiencia cardiaca.

INTRODUCTION AND OBJECTIVES: The prevalence of malnutrition among patients with heart failure and the role it might play in prognosis is not currently known. The aim of this study was to analyse the prevalence and risk of malnutrition as well as its possible influence on long-term mortality in patients with heart failure. METHODS: A prospective analysis was conducted on 208 patients discharged consecutively from our centre between January 2007 and March 2008 after being hospitalised with heart failure. Before discharge, a complete nutritional assessment was performed and diagnosis of malnutrition and risk of malnutrition was done with the Mini Nutritional Assessment. Its possible independent association with mortality was assessed by a Cox multivariate analysis. RESULTS: The mean age of the patients was 73 ± 10 years, with 46% women; the most common aetiology of heart failure was ischaemia (41%). In addition, 13% were classified as malnourished, 59.5% at risk of malnutrition and 27.5% were well-nourished. At a median follow-up of 25 months, mortality in the three groups was 76%, 35.9% and 18.9%, respectively (log-rank, P<.001). In the Cox multivariate analysis, the malnutrition state was an independent predictor of mortality (hazard ratio 3.75, 95% confidence interval, 1.75-8.02, P=.001). CONCLUSIONS: Malnutrition and the risk of malnutrition are highly prevalent in patients hospitalised for heart failure. Furthermore, we found that the state of malnutrition as defined by the Mini Nutritional Assessment survey is an independent predictor of mortality in these patients.

Measurement of aortic valve annulus using different cardiac imaging techniques in transcatheter aortic valve implantation: agreement with finally implanted prosthesis size.

AIMS: To compare the measurements of the aortic annulus obtained with various imaging techniques in patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation, and to determine the grade of agreement between the predicted size of the prosthesis for each technique, and the size of the finally implanted valve. METHODS AND RESULTS: The aortic annulus was measured in 40 patients treated by transcatheter aortic valve implantation (CoreValve aortic valve) with transthoracic (TTE) and transesophageal echocardiography (TEE), 64-slice tomography, and angiography. A large valve was implanted when annulus was >23 mm and a small one if it was ≤23 mm. If the size of the prosthesis predicted by several techniques was not the same in one case, we selected the size in which more techniques presented agreement. Forty aortic valves, 26 small and 14 large, were implanted percutaneously. The best correlation was obtained with TTE and TEE (r = 0.93, P < 0.001). The correlation of TTE and TEE with angiography also was good (r = 0.58, P < 0.001 and r = 0.53, P < 0.001, respectively). Correlations between these techniques and computed tomography were poor (P = NS for all comparisons). The best agreement between estimated aortic annulus and implanted valve size was obtained with transtoracic and TEE (κ= 0.88 and 0.76). CONCLUSIONS: The aortic annulus measurements obtained by TTE, TEE, and angiography correlated well, while tomography correlated poorly with other techniques. The imaging techniques that showed the best agreement between estimated aortic annulus size and implanted aortic valve size were TTE and TEE.

Anomalías cardiacas en el síndrome de LEOPARD / Cardiac abnormalities in LEOPARD syndrome

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Insuficiencia cardiaca aguda en un adulto con flutter auricular 2:1: «¿cebras o caballos?» / Acute heart failure in an adult patient with 2:1 atrial flutter: zebras or horses?

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Colecistectomía videolaparoscópica: experiencia de 3 años en nuestro servicio / Videolaparoscopic cholecystectomy: 3 years of experience in our service

Se describe la experiencia en cirugía videolaparoscópica del Servicio de Clínica Quirúrgica, realizada en un período de 3 años (1995-1998). Se presentan los resultados obtenidos en un grupo de 284 pacientes, 204 de sexo femenino y 80 de sexo masculino, con edades comprendidas entre 16 y 82 años (valor promedio 37.66 años). Los diagnósticos ecográficos se comparan con los hallazgos intraoperatorios y de anatomía patológica. Por estudios ecográficos se diagnostican: litiasis vesiculares (250); colecistitis (23); pólipo vesicular (1); cálculos enclavados en el bacinete (10). En el acto intraoperatorio se confirman: litiasis vesiculares (252), colecistitis (23), hidrops vesicular por cálculos enclavados en bacinete (1), pólipo vesicular (1) y adenocarcinoma de vesícula (1). El número de casos operados por patología fue: 255 litiasis vesiculares (89.80%); 27 colecistitis (9.5%), de los que 21 fueron agudos y 6 crónicos; 1 pólipo vesicular (0.35%); 1 adenocarcinoma de vesícula (0.35%). Se convierten a cirugía convencional 14 casos (4.92%) de los 284 casos estudiados: a) 21.42% por hemorragia intraoperatoria (3/14); b) 42.85% por adherencias múltiples (6/14); c) 14.28% por falta de identificación del conducto cístico (2/14); d) 7.14% por cálculo enclavado en cístico (1/14); e) 14.31% por dificultades técnicas (2/14). Se plantean las ventajas de la cirugía videolaparoscópica con respecto a la cirugía convencional. Palabras claves: cirugía videolaparoscópica, colecistectomía, colecistitis, litiasis vesicular.

The experience in laparoscopic surgery of the Clinical Surgery Unit over a three year period (1995-1998) is described in this paper. The results obtained in a group of 284 patients ­ 204 females and 80 males ­ ranging from 16 to 82 years of age - average value 37.66 years- are presented. Ultrasonic diagnoses are compared to intraoperative and pathologic findings. By means of ultrasonic studies the following pathologies were identified: vesicular lithiasis (250); cholecystitis (23); vesicular polyp (1); pelvis-enclaved calculi (10). During surgery the following pathologies were confirmed: vesicular lithiasis (252), cholecystitis (23), vesicular hydrops due to pelvis-enclaved calculi (1), vesicular polyp (1), and vesicular denocarcinoma (1). The number of cases operated due to the pathologies mentioned was the following: 255 vesicular lithiasis (89.80%); 27 cholecystitis (9.5%) ­ among which, 21 were acute cases and 6 were chronic cases -; 1 vesicular polyp (0.35%); and 1 vesicular adenocarcinoma (0.35%). 14 (4.92%)out of 284 cases studied turn into conventional surgery due to the following reasons: a) 21.42% due to intraoperative hemorrhage (3/14); b) 42.85% due to multiple adherences (6/14); c) 14.28% due to lack of cystic duct identification (2/14); d) 7.14% due to a calculus enclaved in the cyst (1/14); e) 14.31% due to technical difficulties (2/14). The advantages of videolaparoscopic surgery over conventional surgery are also outlined in this paper.