RESUMO
The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous â¼34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations.
Assuntos
Arritmias Cardíacas/genética , Debilidade Muscular/genética , Rabdomiólise/genética , Alelos , Árabes/genética , Arritmias Cardíacas/diagnóstico , Sequência de Bases , Criança , Pré-Escolar , Estresse do Retículo Endoplasmático/genética , Exoma , Éxons , Feminino , Deleção de Genes , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Hispânico ou Latino/genética , Homozigoto , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Debilidade Muscular/diagnóstico , Linhagem , Rabdomiólise/diagnóstico , População Branca/genéticaAssuntos
Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/toxicidade , Iloprosta/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Antibióticos Antineoplásicos/toxicidade , Sobrevivência Celular/fisiologia , Células Cultivadas , Humanos , Miócitos Cardíacos/fisiologia , Inibidores da Agregação Plaquetária/farmacologia , Células-Tronco/fisiologiaRESUMO
In the victims of motor vehicle accidents, unrecognized myocardial injuries may pose diagnostic and therapeutic challenges. Herein, we present a case of a 17-year-old man who developed multiple ventricular premature complexes and nonsustained ventricular tachycardia in the setting of blunt chest trauma from a motor vehicle accident. We discuss significance of the electrocardiographic abnormalities in making an accurate diagnosis of cardiac hematoma and its management.
Assuntos
Derrame Pericárdico/complicações , Taquicardia Ventricular/etiologia , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Acidentes de Trânsito , Adolescente , Ecocardiografia Doppler , Eletrocardiografia/métodos , Seguimentos , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/terapia , Medição de Risco , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/tratamento farmacológico , Traumatismos Torácicos/diagnóstico , Ferimentos não Penetrantes/diagnósticoRESUMO
INTRODUCTION: Although few clinical variables have been associated with recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI) the role of left atrial (LA) mechanical function in the outcome of catheter ablation of AF is not adequately defined. The aim of our study was to determine whether LA mechanical dyssynchrony as evaluated by speckle tracking echocardiography can predict outcome of PVI ablation procedure in patients with paroxysmal AF. METHODS: Twenty-five patients (age 58 ± 11 years, [mean ± standard deviation], 17 males) with paroxysmal AF who met specific enrollment criteria pertaining to clinical presentation and follow-up, assessment of LA mechanical dyssynchrony, and strategy of catheter ablation procedure were enrolled. For LA mechanical dyssynchrony assessment, the time to peak longitudinal strain (TPk) in opposing walls in the midportion of the LA walls at peak atrial contraction in standard two- and four-chamber echocardiographic views by vector velocity imaging (VVI) was measured. Outcome of PVI procedure, whether no recurrence (NR) or AF recurrence (AFR) after 3 months of post-procedural blanking period, was evaluated based on AF-related symptoms and documentation of AF by electrocardiogram, continuous 24-h Holter, and intermittent event monitor recordings. RESULTS: During a follow-up period of 20.3 ± 8.6 months, 18 out of 25 (72 %) patients had no recurrence (NR group), and 7 out of 25 (28 %) patients had recurrence of AF (AFR group). Significant gender difference was observed in terms of outcome such that all AFR patients were men and no woman had recurrence of AF. Between the NR and AFR groups, neither the left atrial diameter, 4.0 ± 0.3 and 4.2 ± 0.2 cm, respectively (p = 0.2), nor the left atrial volume indexes, 45 ± 15 and 48 ± 20 ml/m(2), respectively (p = 0.56), were statistically significantly different. For LA mechanical function, compared to the patients in NR group who had maximum opposing wall TPk delay of 39.9 ± 12.0 ms, those in the AFR group demonstrated significantly more LA mechanical dyssynchrony with maximum opposing wall TPk delay of 64.4 ± 17.0 ms prior to ablation (p = 0.007). Using receiver operative characteristic analyses of the data that had an area under the curve of 0.865, we identified a maximum opposing wall delay cutoff value of 51 ms which predicted AF recurrence with sensitivity and specificity values of 89 and 72 %, respectively (p = 0.005). CONCLUSIONS: Speckle tracking strain analysis echocardiography can evaluate the LA mechanical dyssynchrony quantitatively. The severity of LA mechanical dyssynchrony by VVI can predict the outcome of PVI catheter ablation for paroxysmal AF.
Assuntos
Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Átrios do Coração/diagnóstico por imagem , Veias Pulmonares/cirurgia , Função do Átrio Esquerdo , Ablação por Cateter/métodos , Ecocardiografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Veias Pulmonares/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Cirurgia Assistida por Computador/métodos , Resultado do TratamentoRESUMO
A 63-year-old male radio announcer was admitted with a narrow complex, long RP tachycardia. While in the awake state, the patient spoke in his radio voice, initiating and maintaining the tachycardia. Three-dimensional electroanatomic mapping during electrophysiology study localized the tachycardia to the ostium of the right superior pulmonary vein. After single radiofrequency energy application, no further arrhythmias were inducible with speech. At more than 1 year of follow-up, the patient had no recurrences and continues to work as a radio announcer.
Assuntos
Fala , Taquicardia Supraventricular/etiologia , Ablação por Cateter , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: Photon therapy has been reported to induce resets of implanted cardiac devices, but the clinical sequelae of treating patients with such devices with proton beam therapy (PBT) are not well known. We reviewed the incidence of device malfunctions among patients undergoing PBT. METHODS AND MATERIALS: From March 2009 through July 2012, 42 patients with implanted cardiac implantable electronic devices (CIED; 28 pacemakers and 14 cardioverter-defibrillators) underwent 42 courses of PBT for thoracic (23, 55%), prostate (15, 36%), liver (3, 7%), or base of skull (1, 2%) tumors at a single institution. The median prescribed dose was 74 Gy (relative biological effectiveness; range 46.8-87.5 Gy), and the median distance from the treatment field to the CIED was 10 cm (range 0.8-40 cm). Maximum proton and neutron doses were estimated for each treatment course. All CIEDs were checked before radiation delivery and monitored throughout treatment. RESULTS: Median estimated peak proton and neutron doses to the CIED in all patients were 0.8 Gy (range 0.13-21 Gy) and 346 Sv (range 11-1100 mSv). Six CIED malfunctions occurred in 5 patients (2 pacemakers and 3 defibrillators). Five of these malfunctions were CIED resets, and 1 patient with a defibrillator (in a patient with a liver tumor) had an elective replacement indicator after therapy that was not influenced by radiation. The mean distance from the proton beam to the CIED among devices that reset was 7.0 cm (range 0.9-8 cm), and the mean maximum neutron dose was 655 mSv (range 330-1100 mSv). All resets occurred in patients receiving thoracic PBT and were corrected without clinical incident. The generator for the defibrillator with the elective replacement indicator message was replaced uneventfully after treatment. CONCLUSIONS: The incidence of CIED resets was about 20% among patients receiving PBT to the thorax. We recommend that PBT be avoided in pacing-dependent patients and that patients with any type of CIED receiving thoracic PBT be followed closely.
Assuntos
Desfibriladores Implantáveis , Falha de Equipamento/estatística & dados numéricos , Marca-Passo Artificial , Terapia com Prótons , Contraindicações , Análise de Falha de Equipamento , Humanos , Neoplasias Hepáticas/radioterapia , Masculino , Nêutrons/efeitos adversos , Nêutrons/uso terapêutico , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Estudos Retrospectivos , Neoplasias Torácicas/radioterapiaRESUMO
A 41-year-old woman with metastatic melanoma was admitted to the hospital because of syncopal episodes, which had developed after the administration of an experimental chemotherapy agent that targeted Notch signaling, as part of a phase I clinical trial. Cardiac monitoring revealed recurrent episodes of polymorphic ventricular tachycardia correlating with the patient's syncope. Investigations into the cause of the arrhythmia led to the discovery of metastatic lesions within the left ventricular myocardium. In presenting this case of polymorphic ventricular tachycardia as the antemortem clinical manifestation of metastatic melanoma involving the heart, we discuss the importance of recognizing that cardiac metastases can manifest themselves as arrhythmias in patients with malignant melanoma who are undergoing active anticancer treatment.
Assuntos
Eletrocardiografia , Neoplasias Cardíacas/complicações , Melanoma/complicações , Neoplasias Cutâneas/complicações , Taquicardia Ventricular/etiologia , Adulto , Diagnóstico Diferencial , Feminino , Neoplasias Cardíacas/secundário , Ventrículos do Coração , Humanos , Imagem Cinética por Ressonância Magnética , Melanoma/secundário , Neoplasias Cutâneas/patologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologiaRESUMO
Mitochondrial disorders are genetic diseases that result in a deficiency of energy metabolism (ATP production). A "mitochondrial crisis" can occur in the setting of infection, dehydration, or physiologic stress. The hallmark of a mitochondrial crisis is failure of multiple individual organ systems. The mortality of mitochondrial crisis is high and therapy is supportive but involves a specific strategy of hydration with dextrose-containing IV fluids, avoidance of many medications known to worsen mitochondrial function, and limitations of oxygenation as this can promote free radical production. We report a case of a patient with known mitochondrial disease that presented with a mitochondrial crisis with prominent and life-threatening cardiac manifestations including long QT, ventricular arrhythmias, and acute left ventricular systolic dysfunction in addition to rhabdomyolysis, lactic acidosis, and an acute kidney injury. This patient was managed successfully with a specifically tailored supportive strategy, a high-dose metabolic cocktail, permissive hypoxia, and low-protein diet. At 10 weeks post discharge all electrocardiographic abnormalities resolved and ventricular recovery has been observed. Given the increased survival of this population of patients into adulthood it is important that these adjunctive therapeutic strategies require consideration by clinicians treating this group of patients.
RESUMO
Purulent pericarditis, a localized infection within the pericardial space, has become a rare entity in the modern antibiotic era. Although historically a disease of children and young adults, this is no longer the case: the median age at the time of diagnosis has increased by nearly 30 years over the past 6 decades. Despite advances in diagnostic and treatment modalities, purulent pericarditis remains a life-threatening illness. Unfortunately, the diagnosis is made postmortem in more than half the cases. Thus, a high index of clinical suspicion is crucial. We present 2 cases of purulent pericarditis, and provide an updated review of other case series published over the past 60 years.
Assuntos
Infecções Bacterianas/diagnóstico , Pericardite/diagnóstico , Aneurisma Infectado/diagnóstico , Aneurisma da Aorta Torácica/diagnóstico , Aneurisma da Aorta Torácica/cirurgia , Infecções Bacterianas/cirurgia , Candida glabrata , Candidíase/diagnóstico , Candidíase/cirurgia , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/cirurgia , Terapia Combinada , Quimioterapia Combinada , Feminino , Fluconazol/administração & dosagem , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/cirurgia , Humanos , Infusões Intravenosas , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Penicilinas/administração & dosagem , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/cirurgia , Técnicas de Janela Pericárdica , Pericardiocentese , Pericardite/cirurgia , Propionibacterium acnes , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/cirurgia , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae , Supuração/diagnóstico , Supuração/cirurgia , Tomografia Computadorizada por Raios X , Vancomicina/administração & dosagemRESUMO
BACKGROUND: Abnormalities in left ventricular (LV) relaxation and/or increased filling pressures are indicators of LV diastolic dysfunction in patients with hypertension (HTN). The purpose of this study was to assess clinical use of pulsed wave Doppler, Doppler tissue imaging (DTI), and color M-mode (CMM) indices for determination of diastolic function in patients with HTN. METHODS: In all, 278 ambulatory patients with normal LV systolic function were grouped according to the presence of HTN with and without LV hypertrophy (LVH) (determined by the 2-dimensional area-length method) as follows: healthy control subjects (NC, n = 122), HTN without LVH (HTN, n = 70), and HTN with LVH (HTN+LVH, n = 86). Pulsed wave Doppler-derived measurements included transmitral E- and A-wave velocities, E/A ratio, and deceleration and isovolumic relaxation time intervals; DTI-derived early diastolic (Em) velocities were obtained at 4 LV annular sites. CMM-derived flow propagation velocity and the intraventricular pressure gradient were also calculated. Analysis of covariance adjusted for age and sex of diastolic indices was performed to compare the differences among groups. RESULTS: Only DTI-derived filling pressures demonstrated progressive statistically significant differences among all 3 groups (ie, HTN vs NC, HTN+LVH vs NC, and HTN vs HTN+LVH). However, CMM-derived flow propagation velocity and intraventricular pressure gradient indices were similar among the groups. CONCLUSION: DTI is a robust method compared with pulsed wave Doppler- and CMM-derived indices for the quantitative assessment of LV relaxation and filling pressures in patients with HTN.