Non­synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all­cause death in patients with non­ischemic heart failure.

Sudden cardiac death (SCD) is an unpredictable and common mode of death in patients with heart failure (HF). Alterations in calcium handling may lead to malignant arrhythmias, resulting in SCD, and variants in calcium signaling-related genes have a significant association with SCD. Therefore, the aim of the present retrospective cohort study was to investigate the association of Ser96Ala [histidine-rich calcium-binding protein (HRC)], Ser49Gly [ß1-adrenergic receptor (ADRB1)], Arg389Gly (ADRB1) and Gly1886Ser [ryanodine receptor 2 (RYR2)] polymorphisms with serious arrhythmic events and overall mortality in patients with HF with reduced left ventricular ejection fraction of non-ischemic etiology. In total, 136 patients with HF underwent physical examination, routine laboratory tests, non-invasive assessment of cardiac function and an invasive electrophysiological study. The primary outcome was the occurrence of serious arrhythmic events, set as either SCD or appropriate implantable cardioverter-defibrillator (ICD) therapy, and the secondary outcome was all-cause death. During a median follow-up of 37 months, arrhythmic events occurred in 26 patients (19%) and 41 patients (30%) died. Patients carrying the Ser allele of the Ser96Ala polymorphism in HRC had worse survival than those with the Ala/Ala genotype (log-rank P=0.043). Despite the difference in survival time, the Ala/Ala genotype was not associated with all-cause death in the regression analysis [unadjusted hazard ratio (HR)=0.17; 95% CI, 0.02-1.21]. Regarding the Ser49Gly and Arg389Gly polymorphisms in ADRB1, homozygosity for the major alleles at both sites (Ser49Ser and Arg389Arg) was associated with a two-fold increased risk of all-cause death compared with the other genotype combinations (unadjusted HR=1.98; 95% CI, 1.02-3.82). However, this association was lost after controlling for clinical covariates. No association was observed for the Gly1886Ser polymorphism in RYR2. Overall, the present findings are concurrent with the hypothesis that the Ser96Ala (HRC), Ser49Gly (ADRB1) and Arg389Gly (ADRB1) polymorphisms may be associated with HF prognosis. In particular, the Ser96Ala polymorphism might aid in risk stratification and patient selection for ICD implantation.

Growth/differentiation factor-15 (GDF-15) as a predictor of serious arrhythmic events in patients with nonischemic dilated cardiomyopathy.

INTRODUCTION: Cardiac biomarkers have been proposed as a new tool to improve risk stratification of serious arrhythmic events in patients with heart failure (HF) beyond estimates of left ventricular ejection fraction. Growth differentiation factor (GDF)-15, a stress-induced cytokine, has been found to correlate with markers of myocardial fibrosis and adverse clinical outcomes, but its role as a predictor of arrhythmic events in patients with nonischemic HF is uncertain. METHODS AND RESULTS: A prospective observational study was conducted in 148 nonischemic patients with HF who underwent comprehensive clinical and laboratory evaluation, including measurement of serum GDF-15. The study endpoints were serious arrhythmic events (which included appropriate implantable cardioverter-defibrillator therapy and sudden cardiac death) and all-cause mortality. Mean age of the cohort was 54.8 ± 12.7 years, and mean left ventricular ejection fraction (LVEF) was 27.4% ± 7.5%. During a mean follow-up time of 42 months, arrhythmic events occurred in 28 patients (19%), and 40 patients (27%) died. An increase in serum GDF-15 (log-transformed) correlated linearly with a higher risk of serious arrhythmic events (HR 1.14, 95% CI 1.01-1.28, p = 0.03) even after adjustment for other potential clinical predictors (HR 1.16, 95% CI 1.02-1.32, p = 0.02). GDF-15 was also strongly and independently associated with all-cause mortality (HR 1.17, 1.05-1.31, p = 0.004). CONCLUSION: In this cohort of nonischemic HF patients on optimized medical treatment, serum GDF-15 levels were independently associated with major arrhythmic events and overall mortality. This biomarker may add prognostic information to better stratify the risk of sudden death in this particular population.

Arritmias cardíacas em pacientes com COVID-19 / Cardiac arrhythmias in patients with COVID-19

Resumo Fundamento: A doença pelo novo coronavírus (COVID-19) está associada a manifestações clínicas cardiovasculares, incluindo a ocorrência de arritmias cardíacas. Objetivos: Avaliar a incidência de arritmias cardíacas (taquiarritmia atrial, bradiarritmia e taquicardia ventricular sustentada) e de parada cardiorrespiratória (PCR) em uma coorte de pacientes internados com COVID-19 em hospital universitário terciário. Métodos: Estudo de coorte retrospectivo realizado por meio de revisão dos registros de prontuário médico. Para comparação entre os grupos, foi considerado como estatisticamente significativo valor de P < 0,05. Resultados: Foram incluídos 241 pacientes consecutivos com diagnóstico de COVID-19 (idade média, 57,8 ± 15,0 anos; 51,5% homens; 80,5% de raça branca) e 35,3% com necessidade de ventilação mecânica invasiva (VM). A mortalidade geral foi de 26,6%, sendo de 58,8% entre aqueles em VM. Arritmias cardíacas ocorreram em 8,7% dos pacientes, sendo a mais comum taquiarritmia atrial (76,2%). Pacientes com arritmias apresentaram maior mortalidade, 52,4% versus 24,1% (p=0,005). Em análise multivariada, apenas a presença de insuficiência cardíaca foi associada a maior risco de arritmias ( hazard ratio , 11,9; IC 95%: 3,6-39,5; p<0,001). Durante a internação, 3,3% dos pacientes foram atendidos em PCR, com predomínio de ritmos não chocáveis. Todos os atendidos em PCR evoluíram com óbito durante a internação. Conclusão: A incidência de arritmias cardíacas em pacientes internados com COVID-19 em hospital terciário brasileiro foi de 8,7%, sendo a mais comum taquiarritmias atrial. A presença de insuficiência cardíaca foi associada a maior risco de arritmias. Pacientes com COVID-19 atendidos em PCR apresentam elevada mortalidade.

Abstract Background: The coronavirus disease 2019 (COVID-19) is associated with cardiovascular clinical manifestations, including cardiac arrhythmias. Objective: To assess the incidence of cardiac arrhythmias (atrial tachyarrhythmia, bradyarrhythmia, and sustained ventricular tachycardia) and cardiac arrest (CA) in a cohort of patients hospitalized with COVID-19 in a tertiary university-affiliated hospital. Methods: Cohort study with retrospective analysis of electronic medical records. For comparison between groups, a value of p <0.05 was considered statistically significant Results: We included 241 consecutive patients diagnosed with COVID-19 (mean age, 57.8 ± 15.0 years; 51.5% men; 80.5% white), 35.3% of whom received invasive mechanical ventilation (MV). The overall mortality was 26.6%, being 58.8% among those on MV. Cardiac arrhythmias were identified in 8.7% of the patients, the most common being atrial tachyarrhythmia (76.2%). Patients with arrhythmias had higher mortality (52.4% versus 24.1%, p = 0.005). On multivariate analysis, only the presence of heart failure (HF) was associated with a higher risk of arrhythmias (hazard ratio, 11.9; 95% CI: 3.6-39.5; p <0.001). During hospitalization, 3.3% of the patients experienced CA, with a predominance of non-shockable rhythms. All patients experiencing CA died during hospitalization. Conclusions: The incidence of cardiac arrhythmias in patients admitted with COVID-19 to a Brazilian tertiary hospital was 8.7%, and atrial tachyarrhythmia was the most common. Presence of HF was associated with an increased risk of arrhythmias. Patients with COVID-19 experiencing CA have high mortality.

Cardiac Arrhythmias in Patients with COVID-19. / Arritmias Cardíacas em Pacientes com COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is associated with cardiovascular clinical manifestations, including cardiac arrhythmias. OBJECTIVE: To assess the incidence of cardiac arrhythmias (atrial tachyarrhythmia, bradyarrhythmia, and sustained ventricular tachycardia) and cardiac arrest (CA) in a cohort of patients hospitalized with COVID-19 in a tertiary university-affiliated hospital. METHODS: Cohort study with retrospective analysis of electronic medical records. For comparison between groups, a value of p <0.05 was considered statistically significant. RESULTS: We included 241 consecutive patients diagnosed with COVID-19 (mean age, 57.8 ± 15.0 years; 51.5% men; 80.5% white), 35.3% of whom received invasive mechanical ventilation (MV). The overall mortality was 26.6%, being 58.8% among those on MV. Cardiac arrhythmias were identified in 8.7% of the patients, the most common being atrial tachyarrhythmia (76.2%). Patients with arrhythmias had higher mortality (52.4% versus 24.1%, p = 0.005). On multivariate analysis, only the presence of heart failure (HF) was associated with a higher risk of arrhythmias (hazard ratio, 11.9; 95% CI: 3.6-39.5; p <0.001). During hospitalization, 3.3% of the patients experienced CA, with a predominance of non-shockable rhythms. All patients experiencing CA died during hospitalization. CONCLUSIONS: The incidence of cardiac arrhythmias in patients admitted with COVID-19 to a Brazilian tertiary hospital was 8.7%, and atrial tachyarrhythmia was the most common. Presence of HF was associated with an increased risk of arrhythmias. Patients with COVID-19 experiencing CA have high mortality.

FUNDAMENTO: A doença pelo novo coronavírus (COVID-19) está associada a manifestações clínicas cardiovasculares, incluindo a ocorrência de arritmias cardíacas. OBJETIVOS: Avaliar a incidência de arritmias cardíacas (taquiarritmia atrial, bradiarritmia e taquicardia ventricular sustentada) e de parada cardiorrespiratória (PCR) em uma coorte de pacientes internados com COVID-19 em hospital universitário terciário. MÉTODOS: Estudo de coorte retrospectivo realizado por meio de revisão dos registros de prontuário médico. Para comparação entre os grupos, foi considerado como estatisticamente significativo valor de P < 0,05. RESULTADOS: Foram incluídos 241 pacientes consecutivos com diagnóstico de COVID-19 (idade média, 57,8 ± 15,0 anos; 51,5% homens; 80,5% de raça branca) e 35,3% com necessidade de ventilação mecânica invasiva (VM). A mortalidade geral foi de 26,6%, sendo de 58,8% entre aqueles em VM. Arritmias cardíacas ocorreram em 8,7% dos pacientes, sendo a mais comum taquiarritmia atrial (76,2%). Pacientes com arritmias apresentaram maior mortalidade, 52,4% versus 24,1% (p=0,005). Em análise multivariada, apenas a presença de insuficiência cardíaca foi associada a maior risco de arritmias ( hazard ratio , 11,9; IC 95%: 3,6-39,5; p<0,001). Durante a internação, 3,3% dos pacientes foram atendidos em PCR, com predomínio de ritmos não chocáveis. Todos os atendidos em PCR evoluíram com óbito durante a internação. CONCLUSÃO: A incidência de arritmias cardíacas em pacientes internados com COVID-19 em hospital terciário brasileiro foi de 8,7%, sendo a mais comum taquiarritmias atrial. A presença de insuficiência cardíaca foi associada a maior risco de arritmias. Pacientes com COVID-19 atendidos em PCR apresentam elevada mortalidade.

GDF-15 como Biomarcador em Doenças Cardiovasculares / GDF-15 as a Biomarker in Cardiovascular Disease

Resumo Nos últimos anos, vários biomarcadores estão ganhando importância clínica na avaliação diagnóstica e prognóstica de pacientes com doenças cardiovasculares. O fator de crescimento e diferenciação celular-15 (GDF-15) é uma citocina induzida por estresse e inflamação, membro da família do TGF-, cuja produção no miocárdio foi demonstrada experimentalmente em resposta à injúria isquêmica ou sobrecarga cardíaca. Este novo marcador foi positivamente correlacionado com aumento do risco de eventos cardiovasculares em estudos populacionais e configurou-se preditor independente de mortalidade e prognóstico adverso em pacientes com doença arterial coronariana e insuficiência cardíaca. Este trabalho tem como objetivo revisar o valor diagnóstico e prognóstico do GDF-15 em diferentes cenários na cardiologia.

Abstract In the last years, several diagnostic and prognostic biomarkers have been studied in cardiovascular disease. Growth differentiation factor-15 (GDF-15), a cytokine belonging to the transforming growth factor- (TGF-) family, is highly up-regulated in stress and inflammatory conditions and has been correlated to myocardial injury and pressure cardiac overload in animal models. This new biomarker has been positively correlated with increased risk of cardiovascular events in population studies and shown an independent predictor of mortality in patients with coronary artery disease and heart failure. This review aimed to summarize the current evidence on the diagnostic and prognostic value of GDF-15 in different settings in cardiology.

GDF-15 as a Biomarker in Cardiovascular Disease. / GDF-15 como Biomarcador em Doenças Cardiovasculares.

In the last years, several diagnostic and prognostic biomarkers have been studied in cardiovascular disease. Growth differentiation factor-15 (GDF-15), a cytokine belonging to the transforming growth factor- (TGF-) family, is highly up-regulated in stress and inflammatory conditions and has been correlated to myocardial injury and pressure cardiac overload in animal models. This new biomarker has been positively correlated with increased risk of cardiovascular events in population studies and shown an independent predictor of mortality in patients with coronary artery disease and heart failure. This review aimed to summarize the current evidence on the diagnostic and prognostic value of GDF-15 in different settings in cardiology.

Nos últimos anos, vários biomarcadores estão ganhando importância clínica na avaliação diagnóstica e prognóstica de pacientes com doenças cardiovasculares. O fator de crescimento e diferenciação celular-15 (GDF-15) é uma citocina induzida por estresse e inflamação, membro da família do TGF-, cuja produção no miocárdio foi demonstrada experimentalmente em resposta à injúria isquêmica ou sobrecarga cardíaca. Este novo marcador foi positivamente correlacionado com aumento do risco de eventos cardiovasculares em estudos populacionais e configurou-se preditor independente de mortalidade e prognóstico adverso em pacientes com doença arterial coronariana e insuficiência cardíaca. Este trabalho tem como objetivo revisar o valor diagnóstico e prognóstico do GDF-15 em diferentes cenários na cardiologia.

Tuberculose (TB) miliar após o uso de adalimumabe na doença de Crohn (DC): um relato de caso / Miliar tuberculosis after the use of adalimumab in the Crohn's disease: a case report

O adalimumabe é uma imunoglobulina monoclonal humana que bloqueia os efeitos do TNF alfa, mostrando-se efetivo nas doenças inflamatórias intestinais. É relatado um caso de tuberculose (TB) miliar secundária ao uso de adalimumabe. Paciente feminina, 39 anos, com diagnóstico de Doença de Crohn (DC), prova tuberculínica (PPD) prévio não reator e radiografia de tórax prévia sem particularidades estava em uso contínuo de mesalazina, azatioprina e adalimumabe quando apresentou quadro de febre diária e noturna por 15 dias, associada à sudorese e anorexia. Foi internada para investigação, onde se observou nos exames laboratoriais PCR > 90 e VHS de 60mm. Na tomografia computadorizada (TC) de tórax identificou-se pneumopatia bilateral com aspecto de distribuição miliar e linfonodomegalia mediastinal sugerindo processo infeccioso por TB. A pesquisa de BAAR no escarro (três amostras) foi negativa. O diagnóstico final foi de TB miliar. O tratamento instituído foi com rifampicina, isoniazida, pirazinamida e etambutol. A paciente apresentou boa evolução, recebendo alta hospitalar após sete dias de internação. Necessitou de pausa temporária do uso da azatioprina e do adalimumabe, permanecendo apenas com mesalazina para o tratamento de manutenção da DC e retomou a aplicação de adalimumabe dois meses após o início do tratamento. A exclusão da TB pulmonar latente é obrigatória antes do uso de bloqueadores do TNF-α. No presente relato, a paciente apresentava PPD não reator e uma radiografia de tórax prévia sem particularidades, no entanto apresentou a complicação pulmonar oportunista.

Adalimumab, a human monoclonal immunoglobulin that blocks the effects of tumor necrosis factor alpha (TNF-α), is commonly used for treatment of inflammatory bowel diseases. Here, we report a case of miliary tuberculosis (TB), secondary to the use of adalimumab. A 39 year-old female, undergoing treatment for Crohn's disease (CD) with a drug cocktail comprising mesalazine, azathioprine and adalimumab, exhibited fever for 15 consecutive days accompanied by excessive sweating and anorexia. Prior to initiating treatment for CD, the patient's tuberculin skin test (PPD) was negative and chest x-rays were normal. Upon admission to the hospital for febrile symptoms, blood tests showed C-reactive protein levels >90 and erythrocyte sedimentation rate of 60mm. A CT scan revealed bilateral pneumopathy with miliary dissemination and mediastinal lymphadenopathy, all suggestive of active TB infection. The patient was treated with an antibiotic cocktail consisting of rifampicin, isoniazid, pyrazinamide and ethambutol. During treatment with anitbiotics, mesalazine only was prescribed for managing CD symptoms. The TB infection responded well to the antibiotic cocktail and the patient was discharged after seven days of hospitalization. Adalimumab therapy was re-instated two months after initiation of antibiotic treatment. Although latent TB had been excluded before beginning treatment with TNF-α blockers, this case illustrates that physicians should consider the possibility of opportunistic TB infection when administering immunosuppressive drugs.

Achado incidental de glândula sebácea em colo uterino: provavelmente um processo metaplásico / An incidental finding of sebaceous glands in the uterine cervix: a probable metaplastic process

As glândulas sebáceas ectópicas são achados muito infrequentes no trato genital feminino. Descrevemos um caso que ocorreu em paciente de 42 anos de idade, submetida à histerectomia total, devido à leiomiomatose e ao prolapso uterino.

The ectopic sebaceous glands have been extremely rare findings in female genital system. We describe the case of 42 years-old patient with total hysterectomy due to leiomyomatosis and uterine prolapsed.