Disminución de la reserva de flujo coronario en pacientes con insuficiencia cardíaca no isquémica

Introduction and objectives. Coronary flow reserve (CFR) is impaired not only in ischemic heart disease, but also in cardiac diseases that may or may not course with heart failure. The aim of the present study was to determine if the severity of heart failure can influence CFR impairment. Methods. Forty patients with non-ischemic heart disease and heart failure were studied 41 times. Four groups were established: 1. 10 patients in functional class III-IV; 2. 10 patients in functional class II not taking beta-blockers; 3. 11 patients in class II treated with carvedilol, and 4. 10 patients in class I. These patients had a history of heart failure and systolic dysfunction. Myocardial blood flow (MBF) was measured with positron emission tomography (PET) and N-13 ammonia at rest (r) and during adenosine triphosphate (ATP) infusion. Results. MBF and CFR were significantly higher in group 4 (1.95 ± 0.58 and 2.40 ± 0.95 ml/min/g) than in group 1 (1.02 ± 0.52 and 1.46 ± 0.48 ml/min/g). CFR tended to be higher in groups 2 (1.73 ± 0.72), and 3 (1.89 ± 0.75) vs group 1. No significant correlation was found between CFR and the following variables: age, systolic blood pressure, ventricular mass index, ventricular volume indexes, and ejection fraction. Conclusions. Coronary microvascular function is impaired in non-ischemic heart failure, and the impairment is related to functional class, regardless of the underlying responsible heart disease

Utilización de células madre en terapia regenerativa cardíaca

One of the most important challenges in modern medicine is the use of stem cells for the treatment of human disease such as diabetes, Parkinson ́s disease or isquemic cardiomyopathy. A number of problems need to be solved before stem cells can be applied clinically. In this paper we will review some concepts related to the potential of stem cells, focusing on adult stem cells as they have recently been described by the group of Catherine Verfaillie. We will also present our initial clinical results using adult stem cells for cardiac regenerative therapy. In the studies mentioned above, autologous muscle stem cells (satelite cells) were infused directly in the periphery of the scar tissue of the infarct. We describe the technique for ex vivo expansion and purification of muscle stem cells.La posibilidad de utilizar células madre en el tratamiento de diversas enfermedades humanas como la diabetes, la enfermedad de Parkinson, la cardiopatía isquémica constituye uno de los retos mas importantes de la medicina moderna. Sin embargo, antes de que los resultados de los estudios con células madre se traduzcan clínicamente existen múltiples problemas que deben ser resueltos. A continuación trataremos de exponer algunos conceptos relacionados con las células madre y su potencial, centrándonos principalmente en las células madre adultas tal como han sido recientemente descritas por el grupo de Catherine Verfaillie. Además presentaremos resultados de alguno de los primeros estudios clínicos realizados con células madre adultas como forma de terapia regenerativa cardíaca. En dichos tra- bajos se han empleado células madre de músculo (células satélite) autólogas en pacientes con infarto de miocardio, inyectándose direc- tamente dichas células en la periferia de la cicatriz secundaria al infarto

Can serum hyaluronic acid replace simple non-invasive indexes to predict liver fibrosis in HIV/Hepatitis C coinfected patients?

<p>Abstract</p> <p>Background</p> <p>Hyaluronic acid (HA) serum levels correlate with the histological stages of liver fibrosis in hepatitis C virus (HCV) monoinfected patients, and HA alone has shown very good diagnostic accuracy as a non-invasive assessment of fibrosis and cirrhosis. The aim of this study was to evaluate serum HA levels as a simple non-invasive diagnostic test to predict hepatic fibrosis in HIV/HCV-coinfected patients and to compare its diagnostic performance with other previously published simple non-invasive indexes consisting of routine parameters (HGM-1, HGM-2, Forns, APRI, and FIB-4).</p> <p>Methods</p> <p>We carried out a cross-sectional study on 201 patients who all underwent liver biopsies and had not previously received interferon therapy. Liver fibrosis was determined via METAVIR score. The diagnostic accuracy of HA was assessed by area under the receiver operating characteristic curves (AUROCs).</p> <p>Results</p> <p>The distribution of liver fibrosis in our cohort was 58.2% with significant fibrosis (F≥2), 31.8% with advanced fibrosis (F≥3), and 11.4% with cirrhosis (F4). Values for the AUROC of HA levels corresponding to significant fibrosis (F≥2), advanced fibrosis (F≥3) and cirrhosis (F4) were 0.676, 0.772, and 0.863, respectively. The AUROC values for HA were similar to those for HGM-1, HGM-2, FIB-4, APRI, and Forns indexes. The best diagnostic accuracy of HA was found for the diagnosis of cirrhosis (F4): the value of HA at the low cut-off (1182 ng/mL) excluded cirrhosis (F4) with a negative predictive value of 99% and at the high cut-off (2400 ng/mL) confirmed cirrhosis (F4) with a positive predictive value of 55%. By utilizing these low and high cut-off points for cirrhosis, biopsies could have theoretically been avoided in 52.2% (111/201) of the patients.</p> <p>Conclusions</p> <p>The diagnostic accuracy of serum HA levels increases gradually with the hepatic fibrosis stage. However, HA is better than other simple non-invasive indexes using parameters easily available in routine clinical practice only for the diagnosing of cirrhosis.</p

Progastrin Represses the Alternative Activation of Human Macrophages and Modulates Their Influence on Colon Cancer Epithelial Cells

Macrophage infiltration is a negative prognostic factor for most cancers but gastrointestinal tumors seem to be an exception. The effect of macrophages on cancer progression depends on their phenotype, which may vary between M1 (pro-inflammatory, defensive) to M2 (tolerogenic, pro-tumoral). Gastrointestinal cancers often become an ectopic source of gastrins and macrophages present receptors for these peptides. The aim of the present study is to analyze whether gastrins can affect the pattern of macrophage infiltration in colorectal tumors. We have evaluated the relationship between gastrin expression and the pattern of macrophage infiltration in samples from colorectal cancer and the influence of these peptides on the phenotype of macrophages differentiated from human peripheral monocytes in vitro. The total number of macrophages (CD68+ cells) was similar in tumoral and normal surrounding tissue, but the number of M2 macrophages (CD206+ cells) was significantly higher in the tumor. However, the number of these tumor-associated M2 macrophages correlated negatively with the immunoreactivity for gastrin peptides in tumor epithelial cells. Macrophages differentiated from human peripheral monocytes in the presence of progastrin showed lower levels of M2-markers (CD206, IL10) with normal amounts of M1-markers (CD86, IL12). Progastrin induced similar effects in mature macrophages treated with IL4 to obtain a M2-phenotype or with LPS plus IFNγ to generate M1-macrophages. Macrophages differentiated in the presence of progastrin presented a reduced expression of Wnt ligands and decreased the number and increased cell death of co-cultured colorectal cancer epithelial cells. Our results suggest that progastrin inhibits the acquisition of a M2-phenotype in human macrophages. This effect exerted on tumor associated macrophages may modulate cancer progression and should be taken into account when analyzing the therapeutic value of gastrin immunoneutralization

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Torasemide in chronic heart failure: results of the TORIC study

BACKGROUND: Diuretics such as torasemide are commonly used to treat chronic heart failure (CHF). AIMS: The objective of the TOrasemide In Congestive Heart Failure (TORIC) Study was to investigate the safety, tolerability and efficacy of torasemide in CHF patients compared to furosemide or other diuretics in an open-label, non-randomised, post-marketing surveillance trial. METHODS: The present analysis shows the findings of 1377 patients with New York Heart Association (NYHA) class II-III CHF who received diuretic therapy with torasemide 10 mg/day orally (n=778) vs. patients who received furosemide 40 mg/day orally (n=527) or other diuretics (n=72) on top of their existing standard CHF therapy for 12 months. Besides safety and tolerability, efficacy was assessed by documentation of mortality, morbidity, functional class and serum potassium levels every 3 months. RESULTS: TORIC confirmed the safety and tolerability of torasemide in CHF patients. Mortality was significantly lower in the torasemide (n=17, 2.2%) than in the furosemide/other diuretics group (n=27, 4.5%) (P<0.05). Functional improvement as assessed by NYHA class was observed in more patients who received furosemide torasemide (n=356, 45.8%) than those who received furosemide/other diuretics (n=223, 37.2%) (P=0.00017). At the end of the study abnormally low serum potassium levels were observed in fewer torasemide (n=95, 12.9%) than furosemide/other diuretics patients (n=102, 17.9%) (P=0.013). CONCLUSION: Torasemide is safe and well tolerated in CHF patients. Although not designed as a mortality study, TORIC suggests a lower mortality amongst CHF patients treated with torasemide compared to furosemide/other diuretics. A functional improvement and a lower incidence of abnormal serum potassium levels were also observed in patients receiving torasemide as compared to those receiving furosemide/other diuretics

Torasemide in chronic heart failure: results of the TORIC study

BACKGROUND: Diuretics such as torasemide are commonly used to treat chronic heart failure (CHF). AIMS: The objective of the TOrasemide In Congestive Heart Failure (TORIC) Study was to investigate the safety, tolerability and efficacy of torasemide in CHF patients compared to furosemide or other diuretics in an open-label, non-randomised, post-marketing surveillance trial. METHODS: The present analysis shows the findings of 1377 patients with New York Heart Association (NYHA) class II-III CHF who received diuretic therapy with torasemide 10 mg/day orally (n=778) vs. patients who received furosemide 40 mg/day orally (n=527) or other diuretics (n=72) on top of their existing standard CHF therapy for 12 months. Besides safety and tolerability, efficacy was assessed by documentation of mortality, morbidity, functional class and serum potassium levels every 3 months. RESULTS: TORIC confirmed the safety and tolerability of torasemide in CHF patients. Mortality was significantly lower in the torasemide (n=17, 2.2%) than in the furosemide/other diuretics group (n=27, 4.5%) (P<0.05). Functional improvement as assessed by NYHA class was observed in more patients who received furosemide torasemide (n=356, 45.8%) than those who received furosemide/other diuretics (n=223, 37.2%) (P=0.00017). At the end of the study abnormally low serum potassium levels were observed in fewer torasemide (n=95, 12.9%) than furosemide/other diuretics patients (n=102, 17.9%) (P=0.013). CONCLUSION: Torasemide is safe and well tolerated in CHF patients. Although not designed as a mortality study, TORIC suggests a lower mortality amongst CHF patients treated with torasemide compared to furosemide/other diuretics. A functional improvement and a lower incidence of abnormal serum potassium levels were also observed in patients receiving torasemide as compared to those receiving furosemide/other diuretics