Development of New Drugs to Treat Tuberculosis Based on the Dinitrobenzamide Scaffold.

Tuberculosis (TB) continues to be a major global health challenge and a leading cause of death from infectious diseases. Inspired by the results from a previous work by our group on antimycobacterial N-alkylnitrobenzamides, which are structurally related to the nitrobenzamide family of decaprenylphosphoryl-ß-d-ribose oxidase (DprE1) inhibitors, the present study explored a broad array of substituted benzamides. We particularly focused on previously unexplored 3,5-dinitrobenzamide derivatives. Starting with 3,5-dinitrobenzoic acid, we synthesized a diverse library of amides, incorporating both linear and cyclic amine moieties and also assessed the impact of terminal aromatic groups connected through ether, ester, or amide bonds on the bioactivity of the compounds. The synthesis primarily utilized nucleophilic addition/elimination, SN2, and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of linker. The most interesting compounds (c2, d1, and d2, MIC = 0.031 µg/mL) exhibited activities against Mycobacterium Tuberculosis (Mtb) H37Rv comparable to isoniazid. Complementary computational studies helped elucidate potential interactions with DprE1, enhancing our understanding of the molecular basis of their action. Our findings suggest that the most active compounds provide a promising foundation for the continued development of new antimycobacterial agents.

Synthesis, Activity, Toxicity, and In Silico Studies of New Antimycobacterial N-Alkyl Nitrobenzamides.

Tuberculosis (TB) is a disease that plagues the frailest members of society. We have developed a family of N-alkyl nitrobenzamides that exhibit promising antitubercular activities and can be considered a structural simplification of known inhibitors of decaprenylphosphoryl-ß-D-ribofuranose 2'-oxidase (DprE1), an essential Mycobacterium tuberculosis (Mtb) enzyme and an emergent antitubercular target. Hereby, we report the development of these compounds via a simple synthetic methodology as well as their stability, cytotoxicity, and antitubercular activity. Studying their in vitro activity revealed that the 3,5-dinitro and the 3-nitro-5-trifluoromethyl derivatives were the most active, and within these, the derivatives with intermediate lipophilicities presented the best activities (MIC of 16 ng/mL). Additionally, in an ex vivo macrophage model of infection, the derivatives with chain lengths of six and twelve carbon atoms presented the best results, exhibiting activity profiles comparable to isoniazid. Although the proof is not definite, the assessment of susceptibility over multiple mycobacterial species, together with the structure similarities with known inhibitors of this enzyme, support DprE1 as a likely target of action for the compounds. This idea is also reinforced by the docking studies, where the fit of our more active compounds to the DprE1 binding pocket is very similar to what was observed for known inhibitors like DNB1.

Improving Health Outcomes in Coronary Artery Disease Patients with Short-Term Protocols of High-Intensity Interval Training and Moderate-Intensity Continuous Training: A Community-Based Randomized Controlled Trial.

Studies have shown that the higher the aerobic capacity, the lower the risk of cardiovascular mortality and morbidity. In the case of cardiac patients, high-intensity interval training (HIIT) seems to be more effective than moderate-intensity continuous training (MICT) in improving aerobic capacity. The aim of this study was to investigate the effects of two community-based exercise programs using two short-term protocols (HIIT and MICT) on physical fitness and physical activity (PA) levels in coronary artery disease (CAD) patients. Methods. In this randomized controlled trial, body composition, aerobic capacity, muscle strength, and daily PA levels were assessed before and after 6 weeks of intervention in 69 patients diagnosed with CAD. All patients were randomly (1 : 1 : 1) assigned to two exercise groups (HIIT or MICT) or a control group (no exercise). Both training programs consisted of 6 weeks of supervised treadmill exercise, three sessions per week. MICT targeted ≈70-75% of peak heart rate (HR), while HIIT aimed for ≈85-95% of peak HR. The control group only followed the medical recommendations. Results. Community-based exercise programs showed more positive effects on physical fitness variables and physical activity levels compared to control. HIIT could significantly improve waist circumference, body fat mass, VO2peak, sedentary behavior, and moderate-to-vigorous PA compared to MICT. Moreover, the control group showed poorer results. Conclusion. HIIT can improve health outcomes more positively than MICT and control. These findings indicate that HIIT may be an alternative and effective training method in community-based exercise programs for CAD patients. This trial is registered with NCT03538119.

BUPROPION MISUSE BY NASAL INSUFFLATION WITH A FATAL OUTCOME: CASE REPORT AND REVIEW.

Bupropion is the only FDA - approved synthetic cathinone, with increasing popularity in clinical practice due to its wide range of action, and lack of sexual side effects. However, its stimulant effect similar to amphetamines has growing the concern regarding its recreational use.

Nitrobenzoates and Nitrothiobenzoates with Activity against M. tuberculosis.

Esters of weak acids have shown improved antimycobacterial activity over the corresponding free acids and nitro benzoates in particular have previously shown to have a very intriguing activity. To expand the potential of nitro-derivatives of benzoic acid as antimycobacterial drugs and explore the effects of various structural features on the activity of these compounds, we have obtained a library of 64 derivatives containing esters and thioesters of benzoates and studied their activity against M. tuberculosis, the stability of the compounds, their activation by mycobacterial enzymes and the potential cytotoxicity against human monocytic THP-1 cell line. Our results showed that the most active compounds are those with an aromatic nitro substitution, with the 3,5-dinitro esters series being the most active. Also, the greater antitubercular activity for the nitro derivatives was shown to be unrelated to their pKa values or hydrolysis rates. Given the conventional relationship between nitro-containing substances and toxicity, one might anticipate that the great antimicrobial activity of nitro compounds would be associated with high toxicity; yet, we have not found such a relationship. The nitrobenzoate scaffold, particularly the 3,5-dinitrobenzoate scaffold, merits further investigation, because it has the potential to generate future antimycobacterial agents with improved activity.

Uso indebido de bupropión por insuflación nasal con desenlace fatal: reporte de un caso y revisión / Abuse of bupropion by nasal insufflation with fatal outcome: report of a case and review

Introducción. El bupropión es la única catinona sintética aprobada por la FDA, con una creciente popularidad en la práctica clínica debido a su amplio rango de acción y la falta de efectos secundarios sexuales. Sin embargo, su efecto estimulante similar al de las anfetaminas ha hecho crecer la preocupación respecto a su uso recreativo. Objetivos y métodos. En este manuscrito informamos un caso de uso indebido de bupropión mediante insuflación nasal con desenlace fatal y realizamos una breve revisión deluso recreativo de bupropión. Resultados. Presentamos el caso de un hombre de unos50 años, con abuso prolongado de bupropión principalmente por insuflación nasal, que falleció súbitamente unas dos semanas después de ser dado de alta por un infarto agudo de miocardio tipo 2 secundario a sobredosis de bupropión. A lo largo de las últimas décadas, varios estudios han informado un uso indebido cada vez mayor de bupropión por vías no orales, especialmente a través de la insuflación nasal, y el uso intravenoso, particularmente en pacientes con antecedentes de abuso de sustancias, adolescentes o en entornos penitenciarios. A pesar de que la mayoría de los pacientes tienen efectos secundarios de leves a moderados, consecuencias devastadoras, tales como convulsiones refractarias o shock cardiogénico refractario, pueden ocurrir en caso de sobredosis, lo que exige un reconocimiento oportuno y un enfoque rápido para prevenir estos resultados importantes. En caso de sobredosis, no existe un antídoto específico disponible ni un tratamiento curativo aprobado, su manejo se centra en el tratamiento de los síntomas. Conclusiones. El bupropión es un antidepresivo eficaz, sin embargo, tiene potencial para uso recreativo, especialmente en grupos de alto riesgo. Este documento alerta a todos los médicos sobre el problema emergente relacionado con el uso indebido de bupropión y agrega algunas ideas sobre su reconocimiento y manejo oportunos. (AU)

Xanthogranulomatous pyelonephritis: Case series - Clinical, radiologic, therapeutic, and histological aspects.

Purpose: Xanthogranulomatous pyelonephritis (XGP) is a chronic and severe infection of the kidney. We aimed to review the main clinical, imaging, and histological findings and to assess predictors of surgical complications or hospitalization >10 days (no deaths reported). Materials and Methods: We retrospectively searched all patients with XGP treated at our institution from 2005 to 2019, with 57 patients enrolled. Clinical data were retrieved by a single reader, computed tomographic (CT) examinations by two radiologists, and histopathological specimens by an experienced pathologist. Results: The patients' mean age was 44.3 ± 16.2 years and 41 (71.9%) were female. The most common symptoms were flank/lumbar pain (89.5%), fever (43.9%), and recurrent urinary tract infection (43.9%). The mean time until the presumptive diagnosis was 365.1 days and the median hospitalization period was 11 days. Blood tests showed anemia (78.9%), leukocytosis (43.6%) with left shift (21.6%). Urinalysis showed hematuria (75.6%), bacteriuria (40.9%), and leukocytes (93.2%). Urine cultures showed Escherichia coli in 14.8%, Proteus mirabilis in 7.4%, while 59.3% were negative. Of 40 patients with CT examinations, 38 (95%) presented with hydronephrosis and perinephric inflammatory changes (PIC) and 22 (55%) with Bear Paw sign. PIC was the only independent predictor at multivariate analysis for surgical complications. For prolonged hospitalization, fever and PIC were independent predictors at univariate, but only fever at multivariate analysis. Conclusions: XGP is a worrisome condition, with unclear pathophysiological mechanisms. Fever and PIC at CT examinations were predictors of poor outcomes.

Fluoroquinolone Derivatives in the Treatment of Mycobacterium tuberculosis Infection.

Tuberculosis (TB) is currently one of the leading causes of death due to infective agents, and the growing rate of multidrug-resistant tuberculosis (MDR TB) cases poses an emergent public health threat. Fluoroquinolones are commonly used in the treatment of both MDR TB and drug-sensitive tuberculosis patients who are intolerant to first-line antitubercular agents. Unfortunately, these drugs have mild side effects, relevant to the prolonged treatment regimens and diminished bioavailability due to binding of metal ions. Moreover, the resistance to fluoroquinolones is also on the rise, a characteristic of extensively drug-resistant TB (XDR TB). Here, we developed esters as prodrugs of the fluoroquinolones levofloxacin and ciprofloxacin, with long-chain fatty alcohols. Both the alcohols and the quinolone have previously shown antimycobacterial activity and the aim was to develop esters with improved lipophilicity and capable of delivering the free acid inside mycobacterial cells. The carboxylic acid group of fluoroquinolones is essential to the mode of action but is also responsible for many of its side effects and metal-chelating properties. The synthesis, stability in biological media, and antibacterial activity were evaluated, the latter not only against Mycobacterium tuberculosis but also against other clinically relevant bacterial species, since the parent compounds display a broad spectrum of activity. The biological results show a reduction in the antitubercular activity of the synthesized derivatives, probably due to deficient activation of the ester prodrug. Despite this, it was found that the derivatives exhibit bioactivity against other fluoroquinolone-resistant bacteria, indicating a different mode of action and suggesting that it may be worthwhile to research further modifications to the carboxylic acid group. This might lead to new compounds that are efficient against resistant strains. This idea that the compounds may act by a different mechanism of action was further supported by a brief computer investigation that demonstrated the potential lack of selectivity of the esters to the fluoroquinolone target.

Benzoic Acid Derivatives as Prodrugs for the Treatment of Tuberculosis.

One interesting approach to fight tuberculosis is the use of prodrugs that often have shown improved biological activities over drugs with poor absorption or difficulty to cross membranes. Previous studies demonstrate that weak acids such as benzoic acid, present antimycobacterial activity. Moreover, esters of those acids revealed to be a viable alternative since they may diffuse more easily through the cell membranes. Previously we showed that mycobacteria can easily activate benzoic acid esters by conversion to the corresponding acid. Since Zhang postulated that the activity of the acids can be dependent on their pKa, we set up to synthesize a library of benzoates with different electron withdrawing groups (4-chloro, 2,6-dichloro, 3,5-dichloro, 4-nitro, and 3,5 dinitro), to modulate pKa of the liberated acid and different alkoxy substituents (propyl, hexyl, and phenyl) to modulate their lipophilicity, and tested the activity of the esters and the corresponding free acids against mycobacteria. We also studied the activation of the esters by mycobacterial enzymes and the stability of the compounds in buffer and plasma. We concluded that all the benzoates in our study can be activated by mycobacterial enzymes and that the phenyl and hexyl esters presented higher activity than the corresponding free acids, with the nitrobenzoates, and especially the dinitrobenzoates, showing very interesting antitubercular activity that deserve further exploration. Our results did not show a correlation between the activity and the pKa of the acids.

Influence of Two Exercise Programs on Heart Rate Variability, Body Temperature, Central Nervous System Fatigue, and Cortical Arousal after a Heart Attack.

Cardiovascular diseases (CVD) are the leading cause of death globally. Cardiac rehabilitation (CR) programs' benefits are overall consensual; however, during exercise, progressive physiological effects have not been studied yet in cardiac patients. Our study aims to analyze physiological parameters of thermography, heart rate variability (HRV), blood pressure, central nervous system (CNS) fatigue, and cortical arousal in heart attack patients (HAP) who belong to CR programs of High-Intensity Interval Training (HIIT) and Moderate-intensity Continuous Training (MICT) compared to healthy participants. In this case control study, two HAP patients (both male, age 35 and 48, respectively) and two healthy people (both male, age 38 and 46, respectively) were randomly assigned in a 1:1:1:1 allocation ratio to one of four groups: cardiac MICT, cardiac HIIT, control MICT, and control HIIT. The HIIT at ≈85-95% of peak heart rate (HR) was followed by a one-minute recovery interval at 40% peakHR, and MICT at ≈70-75% of peakHR. Outcome measurements included thermography, HRV, blood pressure, CNS fatigue, and cortical arousal; The HAP presents more than twice the CNS fatigue in MICT than control participants, but HIIT has almost the same CNS fatigue in HAP and control. In addition, both of the HAP groups presented higher temperatures in the chest. The HIIT protocol showed better physiological responses during exercise, compared to MICT in HAP.

Muscular Dystrophy and Heart Failure: An Unusual Association.

Type one muscular dystrophy (DM1) is the most common inherited muscular dystrophy in the adult population. Typically, DM1 presents as myotonia, muscle weakness, cataracts, and cardiac abnormalities, mainly in the conduction system. Although left ventricular dysfunction is not the most common manifestation of DM1, it can be seen with disease progression. The presentation of DM1 as a de novo heart failure is unusual, making its diagnosis a clinical challenge.

Right-Side Endocarditis: A Typical Presentation in an Atypical Patient.

Right-side endocarditis (RSE) is a well-defined clinical entity, rarer than left-side endocarditis. Known risk factors include intravenous drug use or the presence of medical devices. The most frequently affected valve is the tricuspid valve. In most cases, medical treatment is enough. Surgical treatment is reserved for failed medical therapy or in the presence of large vegetations. Although there is a high recurrence rate in intravenous drug users (IDU), RSE has a generally good prognosis. We present the case of a 70-year-old male with no known previous diseases other than alcohol abuse. He was admitted with fever, cough, hemoptysis and a weight loss of 8 kg in two months. Chest X-ray revealed two images of condensation, one in the right pulmonary base and another in the superior right lobe. A computerized tomography of the thorax revealed a subsegmental pulmonary embolism. The patient refused hospitalization and was discharged medicated with levofloxacin and apixaban. In ambulatory, there was a decrease in size of the lesions but with a new lesion in the right hemithorax. Two months after the first episode, the patient is admitted with the same symptoms. The transthoracic echocardiogram showed a 20cm vegetation in the tricuspid valve. He was admitted to the hospital and received treatment with penicillin and gentamicin after isolation of Streptococcus mitis in the blood cultures. Surgical treatment was needed after a weak response to antibiotics, with a good evolution.

High-risk features and predictors of unexplained syncope in the young SCD-SOS cohort.

INTRODUCTION: The Sudden Cardiac Death-Screening of Risk FactOrS survey included a 12-lead electrocardiogram (ECG) plus a digital-based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high-risk features and predictors in this cohort. METHODS AND RESULTS: We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6-40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age < 18 years old (odds ratio [OR] 1.695; 95% confidence interval [CI] 1.26-2.29, p = .001), male gender (OR 1.642; 95% CI 1.22-2.22, p = .001), participation in competitive sports (OR 1.644; 95% CI 1.01-2.66, p = .043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95% CI 1.92-3.40, p < .001), syncope after exertion (OR 2.662; 95% CI 1.73-4.10, p < .001), fever context (OR 9.606; 95% CI 4.13-22.34, p < .001), isolated previous syncopal episode (OR 2.780; 95% CI 0.2.06-3.75, p < .001), and history of palpitations requiring medical care (OR 1.945; 95% CI 1.14-3.31, p = .014). We found no ECG predictors of US in this population. CONCLUSIONS: The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a nonacute setting.

His-bundle pacing as an alternative to CRT in a patient with left bundle branch block, left ventricular dysfunction, and TAVI-induced complete AV block.

Our clinical case supports the effectiveness of distal His-Bundle pacing in obtaining ventricular resynchronization in patients with LBBB and left ventricular dysfunction, particularly in the context of post-TAVI conduction disturbances.

Creatinine variation improves Zwolle score in selecting low-risk patients after ST-segment elevation myocardial infarction.

BACKGROUND: The Zwolle score is recommended to identify ST-segment elevation myocardial infarction (STEMI) patients with low-risk eligible for early discharge. Our aim was to ascertain if creatinine variation (Δ-sCr) would improve Zwolle score in the decision-making of early discharge after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 3296 patients with STEMI that underwent primary PCI were gathered from the Portuguese Registry on Acute Coronary Syndromes. A Modified-Zwolle score, including Δ-sCr, was created and compared with the original Zwolle score. Δ-sCr was also compared between low (Zwolle score ≤3) and non-low-risk patients (Zwolle score >3). The primary endpoint is 30-day mortality and the secondary endpoints are in-hospital mortality and complications. Thirty-day mortality was 1.5% in low-risk patients (35 patients) and 9.2% in non-low-risk patients (92 patients). The Modified-Zwolle score had a better performance than the original Zwolle score in all endpoints: 30-day mortality (area under curve 0.853 versus 0.810, P < 0.001), in-hospital mortality (0.889 versus 0.845, P < 0.001) and complications (0.728 versus 0.719, P = 0.037). Reclassification of patients lead to a net reclassification improvement of 6.8%. Additionally, both original Zwolle score low-risk patients and non-low-risk patients who had a Δ-sCr ≥0.3 mg/dl had higher 30-day mortality (low-risk: 1% versus 6.6%, P < 0.001; non-low-risk 4.4% versus 20.7%, P < 0.001), in-hospital mortality and complications. CONCLUSION: Δ-sCr enhanced the performance of Zwolle score and was associated with higher 30-day mortality, in-hospital mortality and complications in low and non-low-risk patients. This data may assist the selection of low-risk patients who will safely benefit from early discharge after STEMI.

Drug-Induced Liver Injury Induced by Bioflavonoids.

Drug-induced liver injury (DILI) is a relatively rare disease with a vast spectre of clinical manifestations. Its diagnosis is based on the exclusion of other causes of liver disease. The identification of a causal agent is based on the temporal relation between the symptoms and their resolution after stopping the suspected drug. Many drugs have been described as causative agents of DILI; however, bioflavonoids have never been implied with an idiosyncratic DILI in the literature.

Clinical and Echocardiographic Characterization of False-Positive Results from Stress Echocardiography.

BACKGROUND: Stress echocardiography has a 72%-85% sensitivity and an 80%-95% specificity. In this study, we characterized patients who received a false-positive stress echocardiogram result. METHODS: A total of 5,256 patients underwent a stress echocardiogram (induced by exercise, dobutamine, or dipyridamole) between 2009 to 2018, and 405 patients (7.7%) received a positive result. Among the positive patients, 300 underwent coronary angiography within 12 months, and these patients were included in this study (mean age = 64.9 ± 9.4 years, 230 men [76.7%]). Coronary artery disease was diagnosed by stenosis ≥50% in any epicardial coronary artery. Clinical and echocardiographic variables were compared between patients with true- and false-positive stress echocardiogram results. RESULTS: Seventy-two patients (24%) had a false-positive stress echocardiogram, with similar rates across stressor types (p = 0.574). Patients with false positives were less frequently men (63.9% vs. 80.7%, p = 0.003), had lower diabetes mellitus prevalence (15.3% vs. 45.6%, p = 0.001), were similar to true positive patients with regard to body-mass index, arterial hypertension prevalence, hyperlipidemia and smoking, and had lower pre-test probability of coronary artery disease (23% vs. 32%, p = 0.016). The wall motion score index (WMSI) was higher in the true-positive stress group, and wall motion abnormalities were more frequent in the apical segments (70.5% vs. 56.7%, p = 0.034). In a multivariable predictive model, men (odds ratio [OR] = 2.994), diabetes (OR = 5.440), and peak WMSI (OR = 10.690) were associated with a true-positive result. CONCLUSIONS: Twenty-four percent of our study population received a false-positive stress echocardiogram result, with similar rates across stressor types. Patients with true-positive stress echocardiogram results are more likely to be men, diabetic, and have a high peak WMSI.

New-Onset Atrial Fibrillation in St-Segment Elevation Myocardial Infarction: Predictors and Impact on Therapy And Mortality / Fibrilação Auricular de Novo no Infarto Agudo do Miocárdio com Supradesnível do Segmento ST: Preditores e Impacto na Terapêutica e Mortalidade

Abstract Backgrund: New-onset atrial fibrillation complicating acute myocardial infarction represents an important challenge, with prognostic significance. Objective: To study the incidence, impact on therapy and mortality, and to identify predictors of development of new-onset atrial fibrillation during hospital stay for ST-segment elevation myocardial infarction. Methods: We studied all patients with ST-elevation myocardial infarction included consecutively, between 2010 and 2017, in a Portuguese national registry and compared two groups: 1 - no atrial fibrillation and 2 - new-onset atrial fibrillation. We adjusted a logistic regression model data analysis to assess the impact of new-onset atrial fibrillation on in-hospital mortality and to identify independent predictors of its development. A p value < 0.05 was considered significant. Results: We studied 6325 patients, and new-onset atrial fibrillation was found in 365 (5.8%). Reperfusion was successfully accomplished in both groups with no difference regarding type of reperfusion. In group 2, therapy with beta-blockers and angiotensin-conversion enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) was less frequent, 20.6% received anticoagulation at discharge and 16.1% were on triple therapy. New-onset atrial fibrillation was associated with more in-hospital complications and mortality. However, it was not found as an independent predictor of in-hospital mortality. We identified age, prior stroke, inferior myocardial infarction and complete atrioventricular block as independent predictors of new-onset atrial fibrillation. Conclusion: New-onset atrial fibrillation remains a frequent complication of myocardial infarction and is associated with higher rate of complications and in-hospital mortality. Age, prior stroke, inferior myocardial infarction and complete atrioventricular block were independent predictors of new onset atrial fibrillation. Only 36.7% of the patients received anticoagulation at discharge.

Resumo Fundamento: A fibrilação auricular de novo no contexto de infarto agudo do miocárdio representa um importante desafio com potencial impacto prognóstico. Objetivo: Determinar a incidência, impacto na terapêutica e mortalidade, e identificar possíveis preditores do aparecimento de fibrilação auricular de novo durante o internamento por infarto agudo do miocárdio com supradesnivelamento do segmento ST. Métodos: Estudamos todos os pacientes com infarto agudo do miocárdio com supradesnivelamento do segmento ST inseridos consecutivamente de 2010 a 2017 num registro nacional português e comparamos dois grupos: 1 - sem fibrilação auricular; 2- com fibrilação auricular de novo. Efetuamos análise com modelo de regressão logística para avaliar o impacto de fibrilação auricular de novo na mortalidade intra-hospitalar e identificar preditores independentes para o seu aparecimento. Para teste de hipóteses, considerou-se significativo p < 0,05. Resultados: Estudamos 6325 pacientes, dos quais 365 (5.8%) apresentaram fibrilação auricular de novo. Não houve diferença no número de pacientes reperfundidos nem na estratégia de reperfusão. No grupo 2, terapêutica com betabloqueadores e IECA/ARA foi menos frequente, 20.6% tiveram alta sob anticoagulação oral e 16.1% sob terapêutica tripla. A fibrilação auricular de novo associou-se a maior incidência de complicações e mortalidade intra-hospitalar, mas não foi preditor independente de mortalidade intra-hospitalar. Identificamos idade, acidente vascular cerebral prévio, infarto inferior e bloqueio auriculoventricular completo como preditores independentes de fibrilação auricular de novo. Conclusões: A fibrilação auricular de novo continua sendo uma complicação frequente do infarto agudo do miocárdio, estando associada a aumento das complicações e mortalidade intra-hospitalar. Apenas 36.7% desses pacientes teve alta sob anticoagulação.