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The Amulet IDE Trial is an ongoing, prospective, randomized, multi-national trial, designed to evaluate the safety and effectiveness of the AMPLATZER Amulet Left Atrial Appendage Occluder for stroke prevention in comparison to the WATCHMAN Left Atrial Appendage Closure Device in patients with non-valvular atrial fibrillation. METHODS: Non-valvular atrial fibrillation patients at high risk of stroke (CHADS2 score ≥2 or a CHA2DS2-VASc score of ≥3) who are suitable candidates for left atrial appendage occlusion (LAAO) will be fully informed and requested to participate in the trial. A total of 1878 patients at up to 150 sites worldwide will be randomized in a 1:1 ratio between the AMPLATZER Amulet device (investigational) and the Boston Scientific WATCHMAN device (control). Each patient will be followed for 5 years, with follow-up assessments at discharge, 45 days, 3, 6, 9, 12, 18, and 24 months and then annually. The trial has three primary endpoints: A composite of procedure-related complications, or all-cause death, or major bleeding through 12 months (safety); a composite of ischemic stroke or systemic embolism through 18 months (effectiveness); and effective device LAAO, defined as residual jet around the device ≤5 mm at the 45-day visit (mechanism of action). SUMMARY: The Amulet IDE Trial is the first randomized head-to-head LAAO device trial and will provide data for the AMPLATZER Amulet occluder in a population with a high risk of stroke and bleeding.
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Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/instrumentação , Dispositivo para Oclusão Septal , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Causas de Morte , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Complicações Pós-Operatórias , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Dispositivo para Oclusão Septal/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controleRESUMO
OBJECTIVE: Studies have shown that transcranial direct current stimulation (tDCS) has immediate effects on brain activity. The aim of this study was to investigate the potential use of tDCS to regulate obsession-induced anxiety immediately after symptom provocation in patients with refractory obsessive-compulsive disorder (OCD). METHODS: Twelve patients with refractory OCD received cathode, anode, and sham transcranial direct current stimulation over the medial prefrontal cortex conjugant to pharmacological treatment in a crossover design. Before and after the DC stimulation, patients graded the intensity of their anxiety after a short exposure to a provoking stimulus using the visual analogue scale. Clinical questionnaires assessing symptoms severity were also applied before each stimulation mode. RESULTS: We found a statistically significant decrease in the severity of the obsession-induced anxiety (decreased visual analogue scale) as a result of cathode tDCS in comparison with the anode and sham stimulation. Reduction in obsession-induced anxiety was consistent, yet short lasting, and was independent of symptom severity. CONCLUSIONS: Cathode tDCS could be potentially used to regulate obsession-induced anxiety in refractory OCD patients. Further studies are warranted to confirm our results as well as to determine whether tDCS can achieve prolonged benefits in OCD and be of aid in behavioral treatments based on exposure.
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Ansiedade/terapia , Transtorno Obsessivo-Compulsivo/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Estudos Cross-Over , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/psicologia , Projetos Piloto , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: We investigated computed tomography (CT) angiography (CTA) in assessment of left atrial appendage (LAA) stasis and thrombus in preprocedural evaluation for atrial fibrillation (AF) ablation in a large community cohort. METHODS AND RESULTS: We reviewed CTA and transesophageal echocardiographic images obtained in 861 consecutive patients with a history of AF undergoing same-day CTA and transesophageal echocardiogram (TEE) before AF ablation at a single hospital (2006-2013). CTA findings of LAA filling defects from acquisitions without electrocardiogram gating were compared to TEE features of LAA stasis (grade 0-4) and thrombus. Stasis grade 0 or 1 by TEE in the absence of thrombus was defined as a negative result. In addition, LAA peak flow velocity was assessed by TEE. Average age was 61 ± 10 years and 75% were male. On CTA, 161 patients (19%) had LAA filling defects on CTA and 21 had ≥grade 2 stasis on TEE, including two with thrombus, resulting in a positive predictive value of only 13%. However, among 670 CTA-negative patients, 669 (99%) were negative for thrombus or stasis by TEE with one false-negative CTA in a patient with grade 2 stasis by TEE but no thrombus, yielding a negative predictive value of 99.9%. Slow LAA Doppler flow velocity was the most important determinant of false-positive CTA results in multivariate analysis (P < 0.0001) CONCLUSION: LAA filling defects on CT are associated with slow LAA flow velocity. AF patients without LAA filing defects on CT are free of significant stasis and thrombus on TEE. It may be possible to eliminate TEE in up to 80% of AF ablation patients based on negative CTA findings.
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Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/epidemiologia , Angiografia por Tomografia Computadorizada/estatística & dados numéricos , Angiografia Coronária/estatística & dados numéricos , Trombose/diagnóstico por imagem , Trombose/epidemiologia , Comorbidade , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Método Simples-CegoRESUMO
In this review we will discuss the broad spectrum of possible relationships between the fields of neurology and psychiatry alongside weighing the pros and cons of each alternative relationship. This is in the hope that such discussions will allow an informed decision regarding the construction of future relations between these two areas. The possible connections between the areas are discussed in light of possible relationships that exist between the two groups in the mathematical world with reference to the proposed solutions to the psychophysical mind-body problem.
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Encefalopatias/psicologia , Transtornos Mentais/fisiopatologia , Relações Metafísicas Mente-Corpo , Neurologia/história , Psiquiatria/história , Psicofisiologia , História do Século XIX , História do Século XX , Humanos , Relações Interprofissionais , Filosofia Médica , Teoria PsicológicaRESUMO
Previously, we reported on the anti-tumor activities of two designed calix[4]arene-based topomimetics (PTX008 and PTX009) of the amphipathic, angiostatic peptide Anginex. Here, we chemically modified the hydrophobic and hydrophilic faces of PTX008 and PTX009, and discovered new calixarene compounds that are more potent, cytotoxic anti-tumor agents. One of them, PTX013, is particularly effective at inhibiting the growth of several human cancer cell lines, as well as drug resistant cancer cells. Mechanistically, PTX013 induces cell cycle arrest in sub-G1 and G0/G1 phases of e.g. SQ20B cells, a radio-resistant human head and neck carcinoma model. In the syngeneic B16F10 melanoma tumor mouse model, PTX013 (0.5 mg/Kg) inhibits tumor growth by about 50-fold better than parent PTX008. A preliminary pharmacodynamics study strongly suggests that PTX013 exhibits good in vivo exposure and a relatively long half-life. Overall, this research contributes to the discovery of novel therapeutics as potentially useful agents against cancer in the clinic.
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Antineoplásicos/farmacologia , Calixarenos/farmacologia , Citotoxinas/farmacologia , Animais , Antineoplásicos/uso terapêutico , Calixarenos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citotoxinas/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Carga Tumoral/efeitos dos fármacosRESUMO
Activity-dependent neuroprotective protein (ADNP) is one of the lead genes in autism spectrum disorder/intellectual disability. Heterozygous, de novo ADNP mutations cause the ADNP syndrome. Here, to evaluate natural history of the syndrome, mothers of two ADNP syndrome boys aged 6 and a half and two adults aged 27 years (man and woman) were subjected to Vineland III questionnaire assessing adaptive behavior. The boys were assessed again about 2 years after the first measurements. The skill measures, presented as standard scores (SS) included domains of communication, daily living, socialization, motor skills and a sum of adaptive behavior composite. The age equivalent (AE) and growth scale values (GSV) encompassing 11 subdomains assess the age level at which the subject's raw score is found at a norm sample median and the individual temporal progression, respectively. The norm referenced standard scores age-matched, mean 100 ± 15 of the two children showed the lowest outcome in communication (SS: 20-30). Daily living skills presented SS of 50-60, with a possible potential loss of some activities as the child ages, especially in interpersonal relationships with people outside of the immediate family (boy A). In contrast, in socialization, both children were at the SS of 38, with some positive increase to SS of ~ 45 (interpersonal relations with family members and coping skills, depending on the particular individual), 2 years later. Interestingly, there was an apparent large difference in motor skills (gross and fine) at the young age, with subject B showing a relatively higher level of skills (SS: 70), decreasing to subject A level (SS: 40) 2 years later. Together, the adaptive behavior composite suggested a level of SS: 39-48 with B showing a potential increase (SS: 41-44) and A, a substantial decrease (SS: 48-39), suggesting a strong impact of daily living skills. Adults were at SS: 20, which is the lowest possible score. AE showed minor improvements for subject A and B, with all AE values being below 3 years. GSVs for subject A showed some improvement with age, especially in interpersonal, play and leisure, and gross motor subdomains. GSV for subject B showed minor improvements in the various subdomains. Notably, all subjects showed a percentile rank < 1 compared with age-matched norms except for subject B as to motor domain (2nd percentile) at the age of 6 years. In summary, the results, especially comparing SS and AEs between childhood and adulthood, implied a continuous deterioration of activities compared to the general population, encompassing a slower developmental process coupled to possible neurodegeneration, strongly supporting a great need for disease modifying medicinal procedures.
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Atividades Cotidianas , Transtorno do Espectro Autista , Adaptação Psicológica , Adulto , Transtorno do Espectro Autista/genética , Criança , Feminino , Proteínas de Homeodomínio , Humanos , Masculino , Destreza Motora , Proteínas do Tecido Nervoso , Socialização , SíndromeRESUMO
BACKGROUND: GammaTile® (GT) is a recent U.S. Food and Drug Administration (FDA) cleared brachytherapy platform. Here, we report clinical outcomes for recurrent glioblastoma patients after GT treatment following maximal safe resection. METHODS: We prospectively followed twenty-two consecutive Isocitrate Dehydrogenase (IDH) wild-type glioblastoma patients (6 O6-Methylguanine-DNA methyltransferase methylated (MGMTm); sixteen MGMT unmethylated (MGMTu)) who underwent maximal safe resection of recurrent tumor followed by GT placement. RESULTS: The cohort consisted of 14 second and eight third recurrences. In terms of procedural safety, there was one 30-day re-admission (4.5%) for an incisional cerebrospinal fluid leak, which resolved with lumbar drainage. No other wound complications were observed. Six patients (27.2%) declined in Karnofsky Performance Score (KPS) after surgery due to worsening existing deficits. One patient suffered a new-onset seizure postsurgery (4.5%). There was one (4.5%) 30-day mortality from intracranial hemorrhage secondary to heparinization for an ischemic limb. The mean follow-up was 733 days (range 279-1775) from the time of initial diagnosis. Six-month local control (LC6) and twelve-month local control (LC12) were 86 and 81%, respectively. Median progression-free survival (PFS) was comparable for MGMTu and MGMTm patients (~8.0 months). Median overall survival (OS) was 20.0 months for the MGMTu patients and 37.4 months for MGMTm patients. These outcomes compared favorably to data in the published literature and an independent glioblastoma cohort of comparable patients without GT treatment. CONCLUSIONS: This clinical experience supports GT brachytherapy as a treatment option in a multi-modality treatment strategy for recurrent glioblastomas.
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INTRODUCTION: Social cognition refers to how people conceive, perceive, and draw inferences about mental and emotional states of others in the social world. Previous studies suggest that the concept of social cognition involves several abilities, including those related to affect and cognition. The present study analyses the deficits of individuals with schizophrenia in two areas of social cognition: Theory of Mind (ToM) and emotion recognition and processing. Examining the impairment of these abilities in patients with schizophrenia has the potential to elucidate the neurophysiological regions involved in social cognition and may also have the potential to aid rehabilitation. METHODS: Two experiments were conducted. Both included the same five tasks: first- and second-level false-belief ToM tasks, emotion inferencing, understanding of irony, and matrix reasoning (a WAIS-R subtest). The matrix reasoning task was administered to evaluate and control for the association of the other tasks with analytic reasoning skills. Experiment 1 involved factor analysis of the task performance of 75 healthy participants. Experiment 2 compared 30 patients with schizophrenia to an equal number of matched controls. Results. (1) The five tasks were clearly divided into two factors corresponding to the two areas of social cognition, ToM and emotion recognition and processing. (2) Schizophrenics' performance was impaired on all tasks, particularly on those loading heavily on the analytic component (matrix reasoning and second-order ToM). (3) Matrix reasoning, second-level ToM (ToM2), and irony were found to distinguish patients from controls, even when all other tasks that revealed significant impairment in the patients' performance were taken into account. CONCLUSIONS: The two areas of social cognition examined are related to distinct factors. The mechanism for answering ToM questions (especially ToM2) depends on analytic reasoning capabilities, but the difficulties they present to individuals with schizophrenia are due to other components as well. The impairment in social cognition in schizophrenia stems from deficiencies in several mechanisms, including the ability to think analytically and to process emotion information and cues.
Assuntos
Afeto , Cognição , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Comportamento Social , Percepção Social , Teoria da Mente , Adulto , Estudos de Casos e Controles , Análise Fatorial , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Ajustamento Social , Análise e Desempenho de TarefasRESUMO
BACKGROUND: Prolonged QT intervals are reported in patients with COVID-19. Additionally, virus particles in heart tissue and abnormal troponin levels have been reported. Consequently, we hypothesize that cardiac electrophysiologic abnormalities may be associated with COVID-19. METHODS: This is a retrospective study between March 15th, 2020 and May 30th, 2020 of 828 patients with COVID-19 and baseline ECG. Corrected QT (QTc) and QRS intervals were measured from ECGs performed prior to intervention or administration of QT prolonging drugs. QTc and QRS intervals were evaluated as a function of disease severity (patients admitted versus discharged; inpatients admitted to medical unit vs ICU) and cardiac involvement (troponin elevation >0.03 ng/ml, elevated B-natriuretic peptide (BNP) or NT pro-BNP >500 pg/ml). Multivariable analysis was used to test for significance. Odds ratios for predictors of disease severity and mortality were generated. FINDINGS: Baseline QTc of inpatients was prolonged compared to patients discharged (450.1±30.2 versus 423.4±21.7 msec, p<0.0001) and relative to a control group of patients with influenza (p=0.006). Inpatients with abnormal cardiac biomarkers had prolonged QTc and QRS compared to those with normal levels (troponin - QTc: 460.9±34.6 versus 445.3±26.6 msec, p<0.0001, QRS: 98.7±24.6 vs 90.5±16.9 msec, p<0.0001; BNP - QTc: 465.9±33.0 versus 446.0±26.2 msec, p<0.0001, QRS: 103.6±25.3 versus 90.6±17.6 msec, p<0.0001). Findings were confirmed with multivariable analysis (all p<0.05). QTc prolongation independently predicted mortality (8.3% increase in mortality for every 10 msec increase in QTc; OR 1.083, CI [1.002, 1.171], p=0.04). INTERPRETATION: QRS and QTc intervals are early markers for COVID-19 disease progression and mortality. ECG, a readily accessible tool, identifies cardiac involvement and may be used to predict disease course. FUNDING: St. Francis Foundation.
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The burden of coronary artery atherosclerosis in patients with atrial fibrillation (AF) is unknown. We aimed to assess the coronary artery calcium (CAC) in AF patients. We retrospectively analyzed 324 consecutive patients with AF who had CT angiogram before AF ablation and their cardiovascular risk were prospectively collected. Mean age of the cohort was 66 years and 71% were male. The previous history of coronary artery disease (CAD) was present in 19% (nâ¯=â¯63) and CAC was positive in all. In patients without known CAD (nâ¯=â¯261), CAC was present in 70% (nâ¯=â¯182) with a comparable prevalence between men and women, which raised the prevalence of coronary atherosclerosis to 76% (nâ¯=â¯245) for the entire cohort. The median CAC score was 170 (range 1 to 6,157) and largely in multivessel distribution in patients without known CAD. Presence of CAC increased with an increasing number of cardiovascular risk factors. Nevertheless, CAC was present in 58% (nâ¯=â¯40) of patients without conventional cardiovascular risk factors. If CAC score >100 was considered as CAD equivalent as 10-year risk of incident atherosclerotic cardiovascular diseases is >7.5% it would have resulted in higher CAD prevalence of 52% and significant reclassification of CHA2DS2-VASc score in 41% of patients without known CAD. In conclusion, coronary calcium is highly prevalent in AF patients, including those without cardiovascular risk factors. Advanced CAC can potentially shift CHA2DS2-VASc score in many AF patients. Our findings suggest that characterizing CAC in AF may be clinically valuable in thromboembolic risk stratification and management of preventive cardiac therapies.
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Fibrilação Atrial/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Calcificação Vascular/epidemiologia , Idoso , Fibrilação Atrial/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Meios de Contraste , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Incidência , Iohexol , Masculino , Prevalência , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Calcificação Vascular/diagnóstico por imagemRESUMO
Pharmacological treatment of mental disorders is currently decided based on "trial and error" strategy. Mitochondrial multifaceted dysfunction is assumed to be a major factor in the pathophysiology and treatment of schizophrenia (SZ) and bipolar disorder (BD). This study aimed to explore the feasibility of using a profile of mitochondrial function parameters as a tool to predict the optimal drug for an individual patient (personalized medicine). Healthy controls (n = 40), SZ (n = 48) and BD (n = 27) patients were recruited. Mental and global state of the subjects, six mitochondrial respiration parameters and 14 mitochondrial function-related proteins were assessed in fresh lymphocytes following in-vitro or in-vivo treatment with five antipsychotic drugs and two mood-stabilizers. In healthy controls, hierarchal clustering shows a drug-specific effect profile on the different mitochondrial parameters following in-vitro exposure. Similar changes were observed in untreated SZ and BD patients with psychosis. Following a month of treatment of the latter patients, only responders showed a significant correlation between drug-induced in-vitro effect (prior to in-vivo treatment) and short-term in-vivo treatment effect for 45% of the parameters. Long- but not short-term psychotropic treatment normalized mitochondria-related parameters in patients with psychosis. Taken together, these data substantiate mitochondria as a target for psychotropic drugs and provide a proof of concept for selective mitochondrial function-related parameters as a predictive tool for an optimized psychotropic treatment in a given patient. This, however, needs to be repeated with an expanded sample size and additional mitochondria related parameters.
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Antipsicóticos/farmacologia , Transtorno Bipolar/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transtornos Psicóticos/metabolismo , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Biomarcadores , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/etiologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudo de Prova de Conceito , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/etiologia , Psicotrópicos/farmacologia , Psicotrópicos/uso terapêutico , Adulto JovemRESUMO
BACKGROUND: Cardiac injury is common in COVID-19 patients and is associated with increased mortality. However, it remains unclear if reduced cardiac function is associated with cardiac injury, and additionally if mortality risk is increased among those with reduced cardiac function in COVID-19 patients. HYPOTHESIS: The aim of this study was to assess cardiac function among COVID-19 patients with and without biomarkers of cardiac injury and to determine the mortality risk associated with reduced cardiac function. METHODS/RESULTS: This retrospective cohort study analyzed 143 consecutive COVID-19 patients who had an echocardiogram during hospitalization between March 1, 2020 and May 5, 2020. The mean age was 67 ± 16 years. Cardiac troponin-I was available in 131 patients and an increased value (>0.03 ng/dL) was found in 59 patients (45%). Reduced cardiac function, which included reduced left or right ventricular systolic function, was found in 40 patients (28%). Reduced cardiac function was found in 18% of patients without troponin-I elevation, 42% with mild troponin increase (0.04-5.00 ng/dL) and 67% with significant troponin increase (>5 ng/dL). Reduced cardiac function was also present in more than half of the patients on mechanical ventilation or those deceased. The in-hospital mortality of this cohort was 28% (N = 40). Using logistic regression analysis, we found that reduced cardiac function was associated with increased mortality with adjusted odds ratio (95% confidence interval) of 2.65 (1.18 to 5.96). CONCLUSIONS: Reduced cardiac function is highly prevalent among hospitalized COVID-19 patients with biomarkers of myocardial injury and is independently associated with mortality.
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COVID-19/mortalidade , Traumatismos Cardíacos/mortalidade , Troponina I/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , COVID-19/sangue , Causas de Morte , Ecocardiografia Doppler de Pulso , Feminino , Traumatismos Cardíacos/sangue , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos RetrospectivosRESUMO
BACKGROUND: The planar QRS-T angle can be easily obtained from standard 12-lead ECGs, but its predictive ability is not established. We sought to determine the predictive ability of the planar QRS-T angle in patients with nonischemic cardiomyopathy and to assess QRS-T angle behavior over time. METHODS AND RESULTS: Baseline QRS-T angles from 455 patients in the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial were measured. All patients had nonischemic cardiomyopathy, New York Heart Association class I to III heart failure, and nonsustained ventricular tachycardia or frequent ventricular ectopy. The primary end point (a composite of total mortality, appropriate implantable cardioverter-defibrillator shock, or resuscitated cardiac arrest) occurred in 25 of 172 patients (14.5%) with a QRS-T angle < or =90 degrees and in 72 of 283 patients (25.4%) with a QRS-T angle >90 degrees (hazard ratio, 1.93; 95% confidence interval, 1.23 to 3.05; P=0.002). A QRS-T angle >90 degrees remained a significant predictor of the primary end point (P=0.039) after adjustment for treatment group, age, gender, QRS duration, left bundle-branch block, left ventricular ejection fraction, New York Heart Association class III, atrial fibrillation, and diabetes mellitus. The secondary end point (total mortality) occurred in 17 of the 172 patients (9.9%) with a QRS-T angle < or =90 degrees and in 49 of the 283 patients (17.3%) with a QRS-T angle >90 degrees (hazard ratio, 1.79; 95% confidence interval, 1.03 to 3.10; P=0.016). A sample of 152 patients with multiple follow-up ECGs was analyzed to assess temporal QRS-T angle behavior. Changes in the QRS-T angle correlated with changes in left ventricular ejection fraction and QRS duration over time (P<0.001). CONCLUSIONS: A planar QRS-T angle >90 degrees is a significant predictor of a composite end point of death, appropriate implantable cardioverter-defibrillator shock, or resuscitated cardiac arrest in nonpaced, mild to moderately symptomatic patients with nonischemic cardiomyopathy with frequent or complex ventricular ectopy. QRS-T angles changed predictably with left ventricular ejection fraction and QRS duration.
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Cardiomiopatias/diagnóstico , Eletrocardiografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Desfibriladores Implantáveis , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoAssuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno Bipolar/genética , Canais de Cálcio Tipo L/genética , Transtornos Globais do Desenvolvimento Infantil/genética , Transtorno Depressivo Maior/genética , Loci Gênicos/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , HumanosRESUMO
BACKGROUND: Women have been underrepresented in randomized trials of implantable cardioverter defibrillator (ICD) therapy, and limited data suggest that women may not benefit from prophylactic ICD implantation to the same extent as men. In the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a reduction in all-cause mortality was seen in men (P = .018) but not for women (P = .76). METHODS: Sex-specific cumulative probabilities of event-free survival from total, arrhythmic, and noncardiac mortality as well as appropriate shocks were calculated, and log-rank tests were performed. Interaction terms in multivariable Cox proportional hazards models were used to test the hypothesis that the effectiveness of the ICD differed between men and women. RESULTS: Among 458 patients (326 men and 132 women) with nonischemic cardiomyopathy enrolled in the DEFINITE trial, the test for an interaction between sex and ICD treatment on total mortality was not significant in unadjusted (P = .11) or in multivariable adjusted (P = .18) analyses. When we examined cause-specific mortality, we found no sex difference in the incidence of arrhythmic death. Instead, we documented a relative excess of noncardiac death among women randomized to the ICD (P = .02) as compared with women randomized to standard medical therapy. With respect to device use, there was a trend for women to have fewer appropriate ICD shocks after multivariable adjustment (P = .06). CONCLUSION: Among patients with nonischemic cardiomyopathy enrolled in DEFINITE, we found no conclusive evidence for a sex difference in the effectiveness of the ICD; however, the trial was not adequately powered to detect such interaction effects. Larger studies are required to definitively address whether the benefit of ICD therapy differs between men and women.
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Cardiomiopatias/terapia , Desfibriladores Implantáveis , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores Sexuais , Disfunção Ventricular Esquerda/etiologiaRESUMO
It has been suggested that an elevated serum or plasma homocysteine level may be a risk factor for neuropsychiatric conditions such as Alzheimer's disease, schizophrenia, and depression. Because depression is closely related to anxiety disorders, and because it has been suggested that stress may be associated with an elevated homocysteine level, we studied whether serum homocysteine levels are elevated in patients with posttraumatic stress disorder (PTSD). Total serum homocysteine levels in 28 male patients with PTSD were compared to those of 223 healthy controls. The effect of PTSD on the serum homocysteine level was significant (F=42.96, P<.0001). In a regression model for the PTSD patients, the duration of PTSD was found to predict serum homocysteine levels (t=2.228, P=.035). Our results suggest that elevated levels of homocysteine in male patients with PTSD may be related to pathophysiological aspects associated with the chronicity of this disorder.
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Homocisteína/sangue , Transtornos de Estresse Pós-Traumáticos/sangue , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adulto , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/fisiopatologia , Doença Crônica , Depressão/sangue , Depressão/epidemiologia , Depressão/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Esquizofrenia/sangue , Esquizofrenia/epidemiologia , Esquizofrenia/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto JovemRESUMO
The etiopathology of bipolar disorders is yet unraveled and new avenues should be pursued. One such avenue may be based on the assumption that the bipolar broad spectrum includes, among others, an array of rare medical disease entities. Towards this aim we propose a dissecting approach based on a search for rare medical diseases with known etiopathology which also exhibit bipolar disorders symptomatology. We further suggest that the etiopathologic mechanisms underlying such rare medical diseases may also underlie a rare variant of bipolar disorder. Such an assumption may be further reinforced if both the rare medical disease and its bipolar clinical phenotype demonstrate a] a similar mode of inheritance (i.e, autosomal dominant); b] brain involvement; and c] data implicating that the etiopathological mechanisms underlying the rare diseases affect biological processes reported to be associated with bipolar disorders and their treatment. We exemplify our suggested approach by a rare case of autosomal dominant leucodystrophy, a disease entity exhibiting nuclear lamin B1 pathology also presenting bipolar symptomatology.
Assuntos
Transtorno Bipolar/etiologia , Doenças Raras/psicologia , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Humanos , Lamina Tipo B/análise , Fenótipo , Avaliação de SintomasRESUMO
BACKGROUND: Ventricular tachyarrhythmias long enough to cause implantable cardioverter defibrillator (ICD) shocks are generally thought to progress to cardiac arrest. In previous ICD trials, shocks have been considered an appropriate surrogate for sudden cardiac death (SCD) because the number of shocks has been thought to be equivalent to the mortality excess in patients without ICDs. The practice of equating ICD shocks with mortality is controversial and has not been validated critically. METHODS AND RESULTS: The Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial was a prospective, randomized, multicenter trial of ICD therapy in 458 patients with nonischemic cardiomyopathy. Patients were randomized to receive standard medical therapy (STD) or STD plus an ICD. Shock electrograms were reviewed, and the cause of death was evaluated by a separate blinded events committee. There were 15 SCD or cardiac arrests in the STD group and only 3 in the ICD arm. In contrast, of the 229 patients randomized to an ICD, 33 received 70 appropriate ICD shocks. Patients in the ICD arm were more likely to have an arrhythmic event (ICD shock plus SCD) than patients in the STD arm (hazard ratio 2.12, 95% CI 1.153 to 3.893, P=0.013). The number of arrhythmic events when one includes syncope as a potential arrhythmic event was similar in both groups (hazard ratio 1.20, 95% CI 0.774 to 1.865, P=0.414). Approximately the same number of total events was noted in each arm when we compared syncope plus SCD/cardiac arrest in the STD arm with SCD plus ICD shocks plus syncope in the ICD arm. CONCLUSIONS: Appropriate ICD shocks occur more frequently than SCD in patients with nonischemic cardiomyopathy. This suggests that episodes of nonsustained ventricular tachycardia frequently terminate spontaneously in such patients.
Assuntos
Cardiomiopatias/mortalidade , Cardiomiopatias/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Idoso , Cardiomiopatias/complicações , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Síncope , Taquicardia Ventricular/complicações , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/terapia , Fibrilação Ventricular/complicações , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/terapiaRESUMO
BACKGROUND: Patients with nonischemic dilated cardiomyopathy are at substantial risk for sudden death from cardiac causes. However, the value of prophylactic implantation of an implantable cardioverter-defibrillator (ICD) to prevent sudden death in such patients is unknown. METHODS: We enrolled 458 patients with nonischemic dilated cardiomyopathy, a left ventricular ejection fraction of less than 36 percent, and premature ventricular complexes or nonsustained ventricular tachycardia. A total of 229 patients were randomly assigned to receive standard medical therapy, and 229 to receive standard medical therapy plus a single-chamber ICD. RESULTS: Patients were followed for a mean (+/-SD) of 29.0+/-14.4 months. The mean left ventricular ejection fraction was 21 percent. The vast majority of patients were treated with angiotensin-converting-enzyme (ACE) inhibitors (86 percent) and beta-blockers (85 percent). There were 68 deaths: 28 in the ICD group, as compared with 40 in the standard-therapy group (hazard ratio, 0.65; 95 percent confidence interval, 0.40 to 1.06; P=0.08). The mortality rate at two years was 14.1 percent in the standard-therapy group (annual mortality rate, 7 percent) and 7.9 percent in the ICD group. There were 17 sudden deaths from arrhythmia: 3 in the ICD group, as compared with 14 in the standard-therapy group (hazard ratio, 0.20; 95 percent confidence interval, 0.06 to 0.71; P=0.006). CONCLUSIONS: In patients with severe, nonischemic dilated cardiomyopathy who were treated with ACE inhibitors and beta-blockers, the implantation of a cardioverter-defibrillator significantly reduced the risk of sudden death from arrhythmia and was associated with a nonsignificant reduction in the risk of death from any cause.