RESUMEN
In this study, a new series of cis and trans 5-substituted-3-(dibenzyloxyphosphoryl)isoxazolidines 16a-g were synthesized by the 1,3-dipolar cycloaddition reaction of N-benzyl-C-(dibenzyloxyphosphoryl)nitrone and selected N1-allyl-N3-benzylquinazoline-2,4-diones. All the obtained trans-isoxazolidines 16a-g and the samples enriched in respective cis-isomers were evaluated for anticancer activity against three tumor cell lines. All the tested compounds exhibited high activity against the prostate cancer cell line (PC-3). Isoxazolidines trans-16a and trans-16b and diastereoisomeric mixtures of isoxazolidines enriched in cis-isomer using HPLC, namely cis-16a/trans-16a (97:3) and cis-16b/trans-16b (90:10), showed the highest antiproliferative properties towards the PC-3 cell line (IC50 = 9.84 ± 3.69-12.67 ± 3.45 µM). For the most active compounds, induction apoptosis tests and an evaluation of toxicity were conducted. Isoxazolidine trans-16b showed the highest induction of apoptosis. Moreover, the most active compounds turned out safe in vitro as none affected the cell viability in the HEK293, HepG2, and HSF cellular models at all the tested concentrations. The results indicated isoxazolidine trans-16b as a promising new lead structure in the search for effective anticancer drugs.
Asunto(s)
Antineoplásicos , Proliferación Celular , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Isoxazoles/química , Isoxazoles/farmacología , Células PC-3 , Ensayos de Selección de Medicamentos Antitumorales , Quinazolinonas/química , Quinazolinonas/farmacología , Quinazolinonas/síntesis química , Estructura Molecular , Supervivencia Celular/efectos de los fármacos , Apoptosis/efectos de los fármacosRESUMEN
With the 12th highest incidence and a common late diagnostic at advanced stages, neoadjuvant therapies for pancreatic cancer are important, but they require a confirmed diagnosis. Being a diagnostic standard, the clarification of the clinical relevance of needle gauges is needed, as larger ones may retrieve more tissue for diagnostics, but may also increase the risk of complications. We performed a meta-analysis to compare the efficiency of the most commonly used 22-G and 25-G needles for EUS guided biopsy in solid pancreatic lesions. The MEDLINE (via PubMed), Embase, Cochrane (CENTRAL), and Scopus databases were searched with "EUS", "needle", "FNA", "pancreas", "prospective", "22G", and "25G" keywords. Mixed effects were assessed in the model, with a mean of 86% and a 95% confidence interval. Fourteen prospective studies that compared the efficiency of 22-G and 25-G biopsy needles in 508 and 524 lesions, respectively, were analyzed, along with 332 specimens biopsied using both needle sizes. The groups did not significantly differ in the outcomes. A low degree of heterogeneity was observed overall, except for specimen adequacy. Moreover, 22-G and 25-G needles have comparable safety and efficacy for focal pancreatic lesion biopsies without a high risk of complications.
RESUMEN
The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a-d are reported herein. The nitrones 10a-d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTSâ¢+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5-81% after 20 min; 79-96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTSâ¢+ were not significant, since all tested compounds 10a-d showed negligible activity (8-46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC50 = 10 µM).
Asunto(s)
Antioxidantes , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/síntesis química , Lipooxigenasa/metabolismo , Glycine max/enzimología , Glycine max/química , Inhibidores de la Lipooxigenasa/farmacología , Inhibidores de la Lipooxigenasa/química , Inhibidores de la Lipooxigenasa/síntesis química , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Iminas/química , Iminas/farmacología , Compuestos de Bifenilo/química , Compuestos de Bifenilo/antagonistas & inhibidores , Picratos/química , Picratos/antagonistas & inhibidores , Óxidos de Nitrógeno/química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/síntesis químicaRESUMEN
BACKGROUND: Despite its benefits, oral anticoagulant (OAC) therapy in patients with atrial fibrillation (AF) is associated with hemorrhagic complications. AIMS: We aimed to evaluate clinical characteristics of AF patients at high risk of bleeding and the frequency of OAC use as well as identify factors that predict nonuse of OACs in these patients. METHODS: Consecutive AF patients hospitalized for urgent or planned reasons in cardiac centers were prospectively included in the registry in 2019. Patients with HAS-BLED ≥3 (high HAS-BLED group) were assumed to have a high risk of bleeding. RESULTS: Among 3598 patients enrolled in the study, 29.2% were at high risk of bleeding (44.7% female; median [Q1-Q3] age 72 [65-81], CHA2DS2-VASc score 5 [4-6], HAS-BLED 3 [3-4]). In this group, 14.5% of patients did not receive OACs, 68% received NOACs, and 17.5% VKAs. In multivariable analysis, the independent predictors of nonuse of oral OACs were as follows: creatinine level (odds ratio [OR], 1.441; 95% confidence interval [CI], 1.174-1.768; P <0.001), a history of gastrointestinal bleeding (OR, 2.918; 95% CI, 1.395-6.103; P = 0.004), malignant neoplasm (OR, 3.127; 95% CI, 1.332-7.343; P = 0.009), and a history of strokes or transient ischemic attacks (OR, 0.327; 95% CI, 0.166-0.642; P = 0.001). CONCLUSIONS: OACs were used much less frequently in the group with a high HAS-BLED score than in the group with a low score. Independent predictors of nonuse of OACs were creatinine levels, a history of gastrointestinal bleeding, and malignant neoplasms. A history of stroke or transient ischemic attack increased the chances of receiving therapy.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Administración Oral , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Creatinina , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/tratamiento farmacológico , Polonia , Factores de Riesgo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Anciano de 80 o más AñosRESUMEN
One of the main challenges of medicinal chemistry is the search for new substances with antimicrobial potential that could be used in the fight against pathogenic microorganisms. Therefore, the antimicrobial activity of newly synthesized compounds is still being investigated. Carbazole-containing compounds appear to be promising antibacterial, antifungal, and antiviral agents. The aim of this study was to examine the antimicrobial potential and toxicity of newly synthesized isomeric fluorinated 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives. Their antimicrobial activity against bacteria and fungi was tested according to CLSI guidelines. Similarly to previously studied carbazole-containing compounds, the tested derivatives showed the ability to effectively inhibit the growth of Gram-positive bacteria. The addition of carbazole derivatives 2, 4, and 8 at the concentration of 16 µg/mL caused the inhibition of S. aureus growth by over 60%. The MIC value of compounds 2-5 and 7-10 was 32 µg/mL for Staphylococcus strains. Gram-negative strains of E. coli and P. aeruginosa were found to be more resistant to the tested carbazole derivatives. E. coli cells treated with compounds 3 and 8 at a concentration of 64 µg/mL resulted in a greater-than-40% reduction in bacterial growth. In the case of the P. aeruginosa strain, all compounds in the highest concentration that we tested limited growth by 35-42%. Moreover, an over-60% inhibition of fungal growth was observed in the cultures of C. albicans and A. flavus incubated with 64 µg/mL of compounds 2 or 7 and 1 or 4, respectively. The hemolysis of red blood cells after their incubation with the tested carbazole derivatives was in the range of 2-13%. In the case of human fibroblast cells, the toxicity of the tested compounds was higher. Derivative 1, functionalized with fluorine in position 2 and its hydrobromide, was the least toxic. The obtained results indicated the antimicrobial potential of the tested 4-[4-(benzylamino)butoxy]-9H-carbazole derivatives, especially against S. aureus strains; therefore, it is worth further modifying these structures, in order to enhance their activity against pathogenic microorganisms.
Asunto(s)
Escherichia coli , Staphylococcus aureus , Humanos , Antifúngicos/farmacología , Candida albicans , Carbazoles/toxicidad , Pseudomonas aeruginosaRESUMEN
Atrial fibrillation (AF) is associated with an increased risk of stroke. Therefore, patients with AF require appropriate management and anticoagulant therapy. To balance therapy risks and benefits, oral anticoagulants (OAC) treatment should be 'tailored' in patients at a high risk of stroke and bleeding. However, some studies have demonstrated that certain groups of patients do not receive anticoagulants despite the high risk of stroke or thromboembolism. The study aimed to analyse therapeutic methods of stroke prevention in very high-risk patients (CHA2DS2-VASc score of ≥5 in men and ≥6 in women), identify factors predisposing against the use of OACs and assess the administration of anticoagulants before the introduction of non-vitamin K antagonist OAC (NOAC) in 2004-2011 and beyond (years 2012-2019). The analysis covered 2441 patients with AF at a very high thromboembolic risk who were hospitalised in a reference cardiological centre from 2004 to 2019. Data concerning patients' sex, age, comorbidities, type of AF, renal and echocardiographic parameters, reasons for hospitalisation and applied treatment were collected from medical records. HAS-BLED, CHADS2, and CHA2DS2-VASc scores were calculated for all patients. The treatment with oral anticoagulants was compared in the entire population over 2004-2011 and 2012-2019. In this study, a fifth of patients were not treated with OAC. Most patients hospitalised in the years 2012-2019 were treated with OAC. The predictors of not using OAC turned out to be: age of >74 years, heart failure, cancer, paroxysmal AF, and acute coronary syndrome (ACS) or elective coronary angiography/percutaneous coronary intervention (PCI) as a reason for hospitalisation. The introduction of NOAC was associated with a decline in the use of VKA (from 62% to 19.1%) and APT (from 29.1% to 1.3%). This study outlines reasons to initiate OAC treatment in very high-risk patients in clinical practice.
Asunto(s)
Fibrilación Atrial , Intervención Coronaria Percutánea , Accidente Cerebrovascular , Tromboembolia , Masculino , Humanos , Femenino , Anciano , Anticoagulantes , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Polonia/epidemiología , Accidente Cerebrovascular/epidemiología , Hemorragia/complicaciones , Tromboembolia/tratamiento farmacológico , Tromboembolia/epidemiología , Tromboembolia/prevención & control , Administración Oral , Factores de RiesgoRESUMEN
Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021-2022 in relation to Polish healthcare conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include drugs blocking the renin-angiotensin-aldosterone system, preferably angiotensin receptor antagonist/neprilysin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect - options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers - carvedilol and nebivolol), mineralocorticoid receptor antagonist, and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness has been confirmed in numerous prospective randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or the presence of arrhythmias. This article emphasizes the cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction value. We propose practical guidelines for the use of medicines, profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation, or antiplatelet and anticoagulant therapy are also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan, or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF are discussed.
Asunto(s)
Testimonio de Experto , Insuficiencia Cardíaca , Humanos , Estados Unidos , Volumen Sistólico/fisiología , Polonia , Estudios Prospectivos , Función Ventricular Izquierda , Valsartán/uso terapéutico , Combinación de Medicamentos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Aminobutiratos/uso terapéuticoRESUMEN
The diagnosis of metabolic associated fatty liver disease (MAFLD) is significant for patients' prognosis, as the disease accelerates the development of cardiovascular complications and, on the other hand, cardiometabolic conditions are risk factors for the development of fatty liver diseases. This expert opinion presents principles of MAFLD diagnosis and standards of management to reduce cardiovascular risks in patients with MAFLD.
Asunto(s)
Enfermedades Cardiovasculares , Hepatopatías , Humanos , Testimonio de Experto , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Polonia , Factores de Riesgo , Factores de Riesgo de Enfermedad CardiacaRESUMEN
Simple and efficient strategies for the syntheses of enantiomerically enriched functionalized diethyl 2-amino-, 2,3-diamino- and 2-amino-3-hydroxypropylphosphonates have been developed starting from, respectively, N-protected (aziridin-2-yl)methylphosphonates, employing a regioselective aziridine ring-opening reaction with corresponding nucleophiles. Diethyl (R)- and (S)-2-(N-Boc-amino)propylphosphonates were obtained via direct regiospecific hydrogenolysis of the respective enantiomer of (R)- and (S)-N-Boc-(aziridin-2-yl)methylphosphonates. N-Boc-protected (R)- and (S)-2,3-diaminopropylphosphonates were synthesized from (R)- and (S)-N-Bn-(aziridin-2-yl)methylphosphonates via a regiospecific ring-opening reaction with neat trimethylsilyl azide and subsequent reduction of (R)- and (S)-2-(N-Boc-amino)-3-azidopropylphosphonates using triphenylphosphine. On the other hand, treatment of the corresponding (R)- and (S)-N-Bn-(aziridin-2-yl)methylphosphonates with glacial acetic acid led regiospecifically to the formation of (R)- and (S)-2-(N-Bn-amino)-3-acetoxypropylphosphonates.
RESUMEN
Atrial fibrillation (AF) is known to be a significant risk factor for poor prognosis after stroke. In this study, we compared differences in long-term outcomes after ischemic stroke among patients with AF and sinus rhythm (SR). We identified patients admitted to the reference Neurology Center between 1 January 2013 and 30 April 2015, inclusive, with acute ischemic stroke. Of the 1959 surviving patients, 892 were enrolled and followed for five years or until death. We analyzed the risk of stroke recurrence and death between patients with AF and SR at 1, 3, and 5 years after stroke. The rates of death and stroke recurrence were estimated using Kaplan-Meier analysis and multivariate Cox regression. During follow-up, 17.8% of patients died and 14.6% had recurrent stroke. The mortality in the AF group increased relative to the SR group with subsequent years. The risk of death was statistically higher in the AF than SR group at 1 year after stroke (13.5 vs. 7%, p = 0.004). After adjusting for age, stroke severity, and comorbidities, there was also no significant effect of AF on mortality in the first year after stroke (OR = 1.59, p = 0.247). There were no significant differences between the groups in stroke recurrence during follow-up. The results of our study showed that post-stroke patients with AF have a more severe prognosis, although AF itself does not have an independent negative effect on long-term outcomes after stroke. Long-term survival after stroke in patients with AF was strongly associated with age, stroke severity, and heart failure. The impact of other factors on prognosis after stroke in patients with AF should be considered.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/complicaciones , Accidente Cerebrovascular/etiología , Comorbilidad , Hospitalización , Factores de RiesgoRESUMEN
In this study, a series of 48 hybrids of the functionalised 1-[(1H-1,2,3-triazole-4-yl)methyl]quinazoline-2,4-dione 17-22 were synthesised and evaluated for potential antiviral activity. The new hybrids were designed to contain a diethoxyphosphoryl group connected to the triazole moiety via ethylene or propylene linker, and in which the benzyl or benzoyl function is substituted at N3 in the quinazoline-2,4-dione moiety. The Cu(I)-catalyzed Hüisgen dipolar cycloaddition of azidophosphonates 23 and 24 with the respective N1-propargylquinazoline-2,4-diones 26aa-26ag, 26ba-26bg, 27aa-27ad and 27ba-27bd was applied for the syntheses of the designed compounds. All final hybrids 17-22 and N3-functionalised N1-propargylquinazoline-2,4-diones 26 and 27 were subsequently evaluated for their antiviral activity toward a broad range of DNA and RNA viruses. Importantly, hybrids 19be-19bg and 20be-20bg showed profound antiviral activities against Respiratory Syncytial Virus (RSV) with EC50 values in the lower micromolar range, with activity against viral strains of both subtypes (RSV A and B). In addition, several compounds also exerted some weak antiviral activity against varicella zoster virus. Finally, 19 ag was the only compound that showed antiviral potency against human cytomegalovirus, although with rather weak inhibitory activity. Notably, none of the tested compounds was cytotoxic toward uninfected cell lines used for the antiviral assays at a concentration up to 100 µM, returning interesting therapeutic indices for respiratory syncytial virus.
Asunto(s)
Quinazolinas , Virus Sincitial Respiratorio Humano , Humanos , Quinazolinas/farmacología , Antivirales/farmacología , Línea Celular , Triazoles/farmacología , Relación Estructura-ActividadRESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common disease in elderly patients and thromboembolic complication prophylaxis significantly improves the prognosis in these patients. The study assessed the frequency of individual non-vitamin K antagonist oral anticoagulant (NOAC) use among patients ≥75 years and attempted to identify factors predisposing to their prescription. METHODS: The data of patients with non-valvular AF hospitalized in the reference cardiology center between 2011 and 2019 were analyzed. RESULTS: Out of 1443 analyzed patients, 329 (22.8%) received apixaban, 618 (42.8%) dabigatran, and 496 (34.4%) rivaroxaban. The entire population mean age was 82.3 ± 5 years, and 57.9% were females. Independent predictors of apixaban use were age, and bleeding history. Hospitalization for the implantation/reimplantation of a cardiac implantable electronic device (CIED) reduced the chance of apixaban use. Hypertension was a predictor of dabigatran prescription. The chance of using dabigatran decreased with age. Hypertension and bleeding history decreased the chance of rivaroxaban application. CONCLUSIONS: In hospitalized AF patients ≥75 years, dabigatran was the most frequently used NOAC. Age, comorbidities and bleeding risk determined the selection of individual NOACs.
Asunto(s)
Fibrilación Atrial , Hipertensión , Accidente Cerebrovascular , Tromboembolia , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Femenino , Hemorragia/complicaciones , Humanos , Hipertensión/complicaciones , Masculino , Piridonas/uso terapéutico , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/etiología , Tromboembolia/epidemiología , Tromboembolia/prevención & controlRESUMEN
BACKGROUND: The aim of our study was to assess if patients with AF (atrial fibrillation) and a history of ischemic stroke (IS) excessively receive reduced doses of NOACs (non-vitamin K antagonist oral anticoagulants). METHODS: The Polish AF (POL-AF) registry is a prospective, observational, multicenter study, including patients with AF from 10 cardiology hospital centers. In this study we focused on patients with IS in their past. RESULTS: Among 3999 patients enrolled in the POL-AF registry, 479 (12%) had a previous history of IS. Compared to patients without IS history, post-stroke subjects had a higher CHA2DS2-VASc score (median score 7 vs. 4, p < 0.05). Of these subjects, 439 (92%) had anticoagulation therapy, 83 (18.9%) were treated with a vitamin K antagonist (VKA), 135 (30.8%) with rivaroxaban, 112 (25.5%) with dabigatran, and 109 (24.8%) with apixaban. There were a significant number of patients after IS with reduced doses of NOACs (48.9% for rivaroxaban, 45.5% for dabigatran, and 36.7% for apixaban). In many cases, patients were prescribed reduced doses of NOACs without any indication for reduction (28.8% of rivaroxaban use, 56.9% of dabigatran use, and 60.0% of apixaban use-out of reduced dosage groups, p = 0.06). CONCLUSIONS: A significant proportion of AF patients received reduced doses of NOAC after ischemic stroke in a sizeable number of cases, without indication for dose reduction.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular Isquémico , Administración Oral , Anticoagulantes , Fibrilación Atrial/inducido químicamente , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Fibrinolíticos/uso terapéutico , Humanos , Polonia/epidemiología , Estudios Prospectivos , Piridonas , Sistema de Registros , Rivaroxabán/efectos adversosRESUMEN
Dipolar cycloaddition of the N-substituted C-(diethoxyphosphonyl)nitrones with N3-allyl-N1-benzylquinazoline-2,4-diones produced mixtures of diastereoisomeric 3-(diethoxyphosphonyl)isoxazolidines with a N1-benzylquinazoline-2,4-dione unit at C5. The obtained compounds were assessed for antiviral and antibacterial activities. Several compounds showed moderate inhibitory activities against VZV with EC50 values in the range of 12.63-58.48 µM. A mixture of isoxazolidines cis-20c/trans-20c (6:94) was found to be the most active against B. cereus PCM 1948, showing an MIC value 0.625 mg/mL, and also was not mutagenic up to this concentration.
Asunto(s)
Herpes Zóster , Organofosfonatos , Antibacterianos/farmacología , Antivirales/farmacología , Herpesvirus Humano 3 , Humanos , Quinazolinas/farmacologíaRESUMEN
INTRODUCTION: Some patients with atrial fibrillation (AF) develop left atrial appendage thrombus (LAAT) despite receiving anticoagulant treatment. Different scores were proposed to evaluate thromboembolic risk in patients with AF. Risk stratification according to sex is common in clinical practice. OBJECTIVE: We aimed to identify predictors of LAAT separately in men and women treated with dabigatran or rivaroxaban. PATIENTS AND METHODS: This retrospective study included 1256 patients (479 women [38.1%]) with AF who underwent transesophageal echocardiography before electrical cardioversion or catheter ablation, between January 2013 and December 2019, and received dabigatran or rivaroxaban for at least 3 weeks. RESULTS: Multivariable logistic regression analysis revealed nonparoxysmal AF to predict LAAT in women (odds ratio [OR], 9.70; P = 0.002). In men, the predictors were heart failure (OR, 4.14; P = 0.001), diabetes (OR, 2.64; P = 0.002), nonparoxysmal AF (OR, 5.61; P = 0.02), and estimated glomerular filtration rate below 60 ml/min/1.73 m2 (OR, 2.77; P = 0.01). In the receiver operating characteristic curve analysis, the CHA2DS2VASc-RAF score had the highest value for predicting LAAT in women (area under the curve [AUC] = 0.786). In men, CHA2DS2VASc-RAF, CHA2DS2, CHA2DS2VASc, and R2CHADS2 had sufficient predictive value (AUC = 0.786, 0.726, 0.734, and 0.780, respectively). CONCLUSIONS: The predictors of LAAT differ between men and women treated with dabigatran or rivaroxaban. In women, the CHA2DS2VAScRAF score had the highest predictive value, while in men all the scores had equally sufficient predictive value.
Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Cardiopatías , Trombosis , Anticoagulantes/uso terapéutico , Apéndice Atrial/diagnóstico por imagen , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/uso terapéutico , Femenino , Humanos , Masculino , Estudios Retrospectivos , Rivaroxabán/uso terapéutico , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Trombosis/etiologíaRESUMEN
AIMS: The aim of the study was to evaluate the prevalence of left atrial thrombus (LAT) on transoesophageal echocardiography (TOE) in patients with atrial fibrillation or atrial flutter (AF/AFl) with reference to the presence of heart failure (HF) and its subtypes. METHODS AND RESULTS: The research is a sub-study of the multicentre, prospective, observational Left Atrial Thrombus on Transoesophageal Echocardiography (LATTEE) registry, which comprised 3109 consecutive patients with AF/AFl undergoing TOE prior to direct current cardioversion or catheter ablation. TOE parameters, including presence of LAT, were compared between patients with and without HF and across different subtypes of HF, including HF with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF). HF was diagnosed in 1336 patients (43%). HF patients had higher prevalence of LAT than non-HF patients (12.8% vs. 4.4%; P < 0.001). LAT presence increased with more advanced type of systolic dysfunction (HFpEF vs. HFmrEF vs. HFrEF: 7.4% vs. 10.5% vs. 20.3%; P < 0.001). Univariate analysis revealed that HFrEF (odds ratio [OR] 4.13; 95% confidence interval [95% CI]: 3.13-5.46), but not HFmrEF or HFpEF, was associated with the presence of LAT. Multivariable logistic regression indicated that lower left ventricular ejection fraction (OR per 1%: 0.94; 95% CI 0.93-0.95) was an independent predictor of LAT formation. Receiver operator characteristic analysis showed LVEF ≤48% adequately predicted increased risk of LAT presence (area under the curve [AUC] 0.74; P < 0.0001). CONCLUSION: The diagnosis of HFrEF, but neither HFmrEF nor HFpEF, confers a considerable risk of LAT presence despite widespread utilization of adequate anticoagulation.
Asunto(s)
Fibrilación Atrial , Aleteo Atrial , Insuficiencia Cardíaca , Trombosis , Humanos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Aleteo Atrial/complicaciones , Aleteo Atrial/diagnóstico , Aleteo Atrial/epidemiología , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/epidemiología , Pronóstico , Estudios Prospectivos , Volumen Sistólico , Trombosis/diagnóstico , Trombosis/epidemiología , Trombosis/etiología , Función Ventricular IzquierdaRESUMEN
Hyperuricemia is associated with the risk of developing atrial fibrillation (AF) and heart failure. However, coexisting chronic kidney disease and certain cardiovascular drugs make it difficult to determine whether hyperuricemia is a risk factor or merely a marker of pathology. We retrieved data from the Polish Atrial Fibrillation (POL-AF) registry, which included consecutive patients hospitalized with AF from January to December, 2019. We included 829 patients (mean age: 72.7 ± 11.1 years) with data on serum uric acid (UA, mean: 6.56 ± 1.78 mg/dL) and estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2. We found that UA and ejection fraction (EF) were significantly correlated (r = −0.15, p < 0.05), but not EF and eGFR or eGFR and UA. A multiple regression analysis adjusted for age, body mass index, eGFR, and UA, showed that UA was significantly associated with a reduced EF (R2: 0.021; p < 0.001). The UA cut-off indicative of an EF < 40% was 6.69 mg/dL (AUC, area under the curve: 0.607; 95% CI: 0.554−0.660; p = 0.001). Among drugs known to effect UA concentrations, we found that only diuretics were used more frequently in patients with high UA (above the median) than in patients with low UA (77.5% vs. 67%, p < 0.001). Among patients that used diuretics, UA remained significantly correlated with EF. Thus, we showed that reduced EF was associated with UA in patients with AF and normal renal function, independent of eGFR and diuretic use.
Asunto(s)
Fibrilación Atrial , Hiperuricemia , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Diuréticos , Humanos , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Riñón , Persona de Mediana Edad , Sistema de Registros , Factores de Riesgo , Ácido Úrico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: In the recent years, antithrombotic prophylaxis in patients with atrial fibrillation (AF) has changed significantly. The main aim of this study is to assess the temporal trends of antithrombotic therapy and identify factors predisposing oral anticoagulant (OAC) use in stroke prevention in AF patients. METHODS: The present study is a retrospective, observational, single-center study, which includes consecutively hospitalized patients in the reference cardiology center from January 2004 to December 2019. RESULTS: A total of 9656 patients (43.7% female, mean age 71.2 years) with AF between 2004-2019 are included. Among the total study population, in most of the patients (81.1%), OAC therapy was used, antiplatelet (APT) therapy was prescribed for 13.5% patients, heparins for 2.1% patients and 3.3% of patients did not receive any stroke prevention. OAC prescription significantly increased from 61.6% in 2004 to 97.4% in 2019. The independent predictors of OAC prescription were: the period of hospitalization, non-paroxysmal AF, age, hypertension, diabetes mellitus, previous thromboembolism, hospitalization due to electrical cardioversion, ablation or AF without any procedures. CONCLUSIONS: In hospitalized patients with AF, during sixteen years of the study period, a significant increase in OAC use and a decrease in APT use were noted. Factors other than these included in the CHA2DS2-VASc score were independent predictors of OAC use.
Asunto(s)
Fibrilación Atrial , Accidente Cerebrovascular , Administración Oral , Anciano , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Femenino , Humanos , Masculino , Prescripciones , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & controlRESUMEN
All the enantiomers of (1-amino-3-hydroxypropane-1,3-diyl)diphosphonic acid, newly design phosphonate analogues of 4-hydroxyglutamic acids, were obtained. The synthetic strategy involved Abramov reactions of diethyl (R)- and (S)-1-(N-Boc-amino)-3-oxopropylphosphonates with diethyl phosphite, separation of diastereoisomeric [1-(N-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates as O-protected esters, followed by their hydrolysis to the enantiomeric phosphonic acids. The absolute configuration of the enantiomeric phosphonates was established by comparing the 31P NMR chemical shifts of respective (S)-O-methylmandelic acid esters obtained from respective pairs of syn- and anti-[1-(N-Boc-amino)-3-hydroxypropane-1,3-diyl]diphosphonates according to the Spilling rule.