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1.
Europace ; 26(5)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38584469

RESUMO

AIMS: Brugada syndrome (BrS) diagnosis and risk stratification rely on the presence of a spontaneous type 1 (spT1) electrocardiogram (ECG) pattern; however, its spontaneous fluctuations may lead to misdiagnosis and risk underestimation. This study aims to assess the role for repeat high precordial lead (HPL) resting and ambulatory ECG monitoring in identifying a spT1, and evaluate its prognostic role. METHODS AND RESULTS: HPL resting and ambulatory monitoring ECGs of BrS subjects were reviewed retrospectively, and the presence of a spT1 associated with ventricular dysrhythmias and sudden cardiac death (SCD). Three-hundred and fifty-eight subjects (77 with spT1 pattern at presentation, Group 1, and 281 without, Group 2) were included. In total, 1651 resting HPL resting and 621 ambulatory monitoring ECGs were available for review, or adequately described. Over a median follow-up of 72 months (interquartile range - IQR - 75), 42/77 (55%) subjects in Group 1 showed a spT1 in at least one ECG. In Group 2, 36/281 subjects (13%) had a newly detected spT1 (1.9 per 100 person-year) and 23 on an HPL ambulatory recording (8%). Seven previously asymptomatic subjects, five of whom had a spT1 (four at presentation and one at follow-up), experienced arrhythmic events; survival analysis indicated that a spT1, either at presentation or during lifetime, was associated with events. Univariate models showed that a spT1 was consistently associated with increased risk [spT1 at presentation: hazard ratio (HR) 6.3, 95% confidence interval (CI) 1.4-28, P = 0.016; spT1 at follow-up: HR 3.1, 95% CI 1.3-7.2, P = 0.008]. CONCLUSION: Repeated ECG evaluation and HPL ambulatory monitoring are vital in identifying transient spT1 Brugada pattern and its associated risk.


Assuntos
Síndrome de Brugada , Morte Súbita Cardíaca , Eletrocardiografia Ambulatorial , Humanos , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatologia , Masculino , Feminino , Eletrocardiografia Ambulatorial/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Adulto , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Medição de Risco , Valor Preditivo dos Testes , Fatores de Risco , Frequência Cardíaca , Idoso
2.
PLoS Pathog ; 11(5): e1004917, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25996154

RESUMO

Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Interações Hospedeiro-Patógeno , Metaloproteinase 8 da Matriz/metabolismo , Mycobacterium tuberculosis/fisiologia , Neutrófilos/enzimologia , Tuberculose Pulmonar/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Adulto , Células Cultivadas , Estudos de Coortes , Inibidores Enzimáticos/farmacologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Imunidade Inata/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Metaloproteinase 8 da Matriz/química , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Escarro/enzimologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia
3.
J Cardiovasc Magn Reson ; 17: 64, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26219660

RESUMO

BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point. RESULTS: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls. CONCLUSIONS: Septal convexity is an additional previously undescribed feature of subclinical HCM.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Ventrículos do Coração/patologia , Imagem Cinética por Ressonância Magnética , Adolescente , Adulto , Doenças Assintomáticas , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Valor Preditivo dos Testes , Volume Sistólico , Função Ventricular Esquerda , Adulto Jovem
4.
Heart Rhythm ; 19(1): 70-78, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34487893

RESUMO

BACKGROUND: Experience with implantable loop recorders (ILRs) in Brugada syndrome (BrS) is limited. OBJECTIVE: The purpose of this study was to evaluate the indications and yield of ILR monitoring in a single-center BrS registry. METHODS: Demographic, clinical and follow-up data of BrS patients with ILR were collected. RESULTS: Of 415 BrS patients recruited consecutively, 50 (12%) received an ILR (58% male). Mean age at ILR implantation was 44 ± 15 years. Thirty-one (62%) had experienced syncopal or presyncopal episodes, and 23 (46%) had palpitations. During median follow-up of 28 months (range 1-68), actionable events were detected in 11 subjects (22%); 7 had recurrences of syncope/presyncope, with 4 showing defects in sinus node function or atrioventricular conduction. New supraventricular tachyarrhythmias were recorded in 6 subjects; a run of fast nonsustained ventricular tachycardia was detected in 1 patient. Patients implanted with an ILR were less likely to show a spontaneous type 1 pattern or depolarization electrocardiographic (ECG) abnormalities compared to those receiving a primary prevention implantable-cardioverter defibrillator. Age at implantation, gender, Shanghai score, and ECG parameters did not differ between subjects with and those without actionable events. ILR-related complications occurred in 3 cases (6%). CONCLUSION: In a large cohort of BrS patients, continuous ILR monitoring yielded a diagnosis of tachy- or bradyarrhythmic episodes in 22% of cases. Recurrences of syncope were associated with bradyarrhythmic events. Use of ILR can be helpful in guiding the management of low-/intermediate-risk BrS patients and ascertaining the cause of unexplained syncope.


Assuntos
Síndrome de Brugada/fisiopatologia , Eletrocardiografia Ambulatorial/instrumentação , Síncope/diagnóstico , Síncope/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
5.
Eur Heart J ; 30(21): 2599-605, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19689975

RESUMO

BACKGROUND: Non-sustained ventricular tachycardia (NSVT) during ambulatory electrocardiographic monitoring (typically occurring at rest or during sleep) is associated with an increased risk of sudden cardiac death in patients with hypertrophic cardiomyopathy. The prevalence and prognostic significance of ventricular arrhythmias during exercise is unknown. METHODS AND RESULTS: This was a cohort study, with prospective data collection. We studied 1380 patients, referred to a cardiomyopathy clinic in London, UK [mean age 42 years (SD 15); 62% male; mean follow-up 54 (SD 49) months]. Patients underwent two-dimensional and Doppler echocardiography, upright exercise testing, and Holter monitoring. Twenty-seven patients [mean age 40 (SD 14) years (18-64); 22 (81.5%) male] had NSVT (24) or ventricular fibrillation (VF) (3) during exercise. During exercise, 13 (54.2%) had more than one run of NSVT (maximum 5) with a mean heart rate of 221 (SD 48) b.p.m. Patients with exercise NSVT/VF had more severe hypertrophy (22.6 vs. 19.5 mm, P = 0.009) and larger left atria (47.3 vs. 43.7 mm, P = 0.03). Male gender was significantly associated with exercise NSVT/VF [22 (81.5%) vs. 832 (61.5%), P = 0.03]. Eight (29.6%) of the exercise NSVT/VF patients died or had a cardiac event (SD/ICD discharge/transplant) compared with 150 (11.1%) patients without exercise NSVT/VF, P = 0.008. Patients with NSVT/VF had a 3.73-fold increase in risk of SD/ICD discharge (HR 95% CI: 1.61-8.63, P = 0.002). Exercise NSVT alone was associated with a 2.82-fold increased risk (HR 95% CI: 1.02-7.75, P = 0.049). In multivariable analysis with other risk markers, exercise NSVT/VF (but not NSVT alone) was independently associated with an increased risk of SD/ICD [HR 3.14 (95% CI: 1.29-7.61, P = 0.01)]. CONCLUSION: Ventricular arrhythmia during symptom limited exercise is rare in patients with hypertrophic cardiomyopathy, but is associated with an increased risk of sudden cardiac death.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatia Hipertrófica/complicações , Morte Súbita Cardíaca/etiologia , Exercício Físico/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/mortalidade , Cardiomiopatia Hipertrófica/mortalidade , Eletrocardiografia Ambulatorial , Teste de Esforço , Feminino , Insuficiência Cardíaca/etiologia , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Adulto Jovem
7.
Int J Cardiovasc Imaging ; 32(4): 593-601, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26608801

RESUMO

The aim of this cohort study was to evaluate the value of echocardiographic multilayer strain analysis in the identification of arrhythmogenic cardiomyopathy (AC) in its earliest stages in which sudden cardiac death can occurs. Twenty seven asymptomatic relatives of AC probands (mean age 39.6 ± 19.5 years, 37 % male) with a desmosomal pathogenic mutation but no additional criteria for AC (group II) were compared to age and sex-matched healthy controls (group I). In addition, 70 patients harboring a pathogenic desmosomal mutation with "definitive" diagnosis of AC (group IV), and 19 subjects with "borderline" diagnosis (group III) were also studied. A standard echocardiographic evaluation plus left (LV) and right ventricular global and regional transmural, endocardial, and epicardial longitudinal strain (LS) analysis, was performed. In group II, while LV ejection fraction, fractional shortening, and S' were not significantly reduced compared to controls, transmural global LS was significantly reduced to 19.3 ± 1.8 % in group II versus 20.9 ± 1.1 % in controls (p = 0.0003). Compared to controls, group II presented significant (p < 0.05) regional LS decrease in the basal infero-lateral, antero-lateral, latero-apical, infero-septal, and septo-apical segments. Moreover, LS of the latero-apical and the basal antero-lateral segments was significantly altered in the epicardium (p < 0.05) but not significantly in the endocardium. Global and regional LV LS analysis allows detection of AC in an early or non-diagnostic stage of the disease. Moreover, epicardial LS analysis allows the detection of abnormalities earlier than endocardial LS.


Assuntos
Arritmias Cardíacas/complicações , Cardiomiopatias/diagnóstico por imagem , Ecocardiografia Doppler , Pericárdio/diagnóstico por imagem , Função Ventricular Esquerda , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Pericárdio/fisiopatologia , Valor Preditivo dos Testes , Estresse Mecânico , Volume Sistólico , Adulto Jovem
8.
Heart ; 102(10): 741-7, 2016 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-26857213

RESUMO

OBJECTIVE: We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures. METHODS: Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006-2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF. RESULTS: Mean age was 50.0±15.0 years; 322 (68%) were men. At a median of 4.3 years (IQR 0.1-7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine-Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III-IV, LV end-systolic volume, E/E', and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035). CONCLUSIONS: In patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes.


Assuntos
Cardiomiopatia Hipertrófica/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Contração Miocárdica , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Adulto , Idoso , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/terapia , Causas de Morte , Ecocardiografia Doppler em Cores , Ecocardiografia Doppler de Pulso , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Londres , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Estresse Mecânico , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/terapia
9.
Heart ; 99(8): 534-41, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23339826

RESUMO

AIMS: Sudden cardiac death (SCD) is a common mode of death in hypertrophic cardiomyopathy (HCM), but identification of patients who are at a high risk of SCD is challenging as current risk stratification guidelines have never been formally validated. The objective of this study was to assess the power of the 2003 American College of Cardiology (ACC)/European Society of Cardiology (ESC) and 2011 ACC Foundation (ACCF)/American Heart Association (AHA) SCD risk stratification algorithms to distinguish high risk patients who might be eligible for an implantable cardioverter defibrillator (ICD) from low risk individuals. METHODS AND RESULTS: We studied 1606 consecutively evaluated HCM patients in an observational, retrospective cohort study. Five risk factors (RF) for SCD were assessed: non-sustained ventricular tachycardia, severe left ventricular hypertrophy, family history of SCD, unexplained syncope and abnormal blood pressure response to exercise. During a follow-up period of 11 712 patient years (median 6.6 years), SCD/appropriate ICD shock occurred in 20 (3%) of 660 patients without RF (annual rate 0.45%), 31 (4.8%) of 636 patients with 1 RF (annual rate 0.65%), 27 (10.8%) of 249 patients with 2 RF (annual rate 1.3%), 7 (13.7%) of 51 patients with 3 RF (annual rate 1.9%) and 4 (40%) of 10 patients with ≥4 RF (annual rate 5.0%). The risk of SCD increased with multiple RF (2 RF: HR 2.87, p≤0.001; 3 RF: HR 4.32, p=0.001; ≥4 RF: HR 11.37, p<0.0001), but not with a single RF (HR 1.43 p=0.21). The area under time-dependent receiver operating characteristic curves (representing the probability of correctly identifying a patient at risk of SCD on the basis of RF profile) was 0.63 at 1 year and 0.64 at 5 years for the 2003 ACC/ESC algorithm and 0.61 at 1 year and 0.63 at 5 years for the 2011 ACCF/AHA algorithm. CONCLUSIONS: The risk of SCD increases with the aggregation of RF. The 2003 ACC/ESC and 2011 ACCF/AHA guidelines distinguish high from low risk individuals with limited power.


Assuntos
Algoritmos , Cardiomiopatia Hipertrófica/terapia , Procedimentos Clínicos , Morte Súbita Cardíaca/prevenção & controle , Técnicas de Apoio para a Decisão , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Adulto , American Heart Association , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/mortalidade , Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis/efeitos adversos , Cardioversão Elétrica/efeitos adversos , Falha de Equipamento , Feminino , Humanos , Estimativa de Kaplan-Meier , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Sociedades Médicas/normas , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
11.
Eur J Heart Fail ; 12(2): 114-21, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20083621

RESUMO

AIMS: The prevalence and natural history of cardiovascular disease in adult patients with respiratory chain disease (RCD) is poorly characterized. We sought to determine the frequency and natural history of cardiac disease in patients with primary RCD. METHODS AND RESULTS: Thirty-two patients (37.8 + or - 12.6 years) with a definite diagnosis of RCD underwent clinical examination, electrocardiography (ECG), 24 h Holter ECG, and cardiopulmonary exercise testing. Patients were classified into six different phenotypes: mitochondrial myopathy (MM; n = 8), chronic progressive ophthalmoplegia (CPEO; n = 2), chronic progressive ophthalmoplegia with myopathy (CPEO + MM; n = 12), Kearns-Sayre syndrome (KSS; n = 2), mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS; n = 7), myoclonic epilepsy with ragged red fibres (MERRF, n = 1). [corrected] Twenty-two patients (69%) had a mitochondrial DNA mutation. Twenty-six patients (81%) had evidence for cardiac involvement: ECG abnormalities (69%) and cardiomyopathy (hypertrophic 19%; restrictive 3%; left ventricular non-compaction 3%). During follow-up (4.1 + or - 2.8 years), two patients with CPEO + MM developed hypertrophic cardiomyopathy and one patient with NARP developed peripartum dilated cardiomyopathy. Four patients (KSS = 2; MM = 1; MELAS = 1) developed arrhythmias or syncope requiring device therapy or invasive procedures. One patient with MM and cardiomyopathy had an orthotopic heart transplant. One patient with CPEO + MM died from respiratory failure. Freedom from all cardiovascular events at 5 years was 67% (95% CI 47.4-86.6). CONCLUSION: All patients with RCD should undergo careful and repeated clinical assessment to diagnose and manage cardiovascular involvement. However, life-threatening cardiovascular complications rarely occur, and the prognosis is generally favourable.


Assuntos
Cardiomiopatias/epidemiologia , Doenças Mitocondriais/complicações , Adolescente , Adulto , Cardiomiopatias/diagnóstico , Cardiomiopatias/etiologia , Intervalos de Confiança , DNA Mitocondrial/genética , Eletrocardiografia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/epidemiologia , Fenótipo , Prevalência , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia , Adulto Jovem
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