RESUMEN
OBJECTIVES: The aim of this study was to evaluate whether cardiac biomarkers, tissue velocity (TVI) and strain imaging, and cardiac magnetic resonance imaging can predict early left ventricular (LV) dysfunction in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting. BACKGROUND: Early indexes of LV systolic dysfunction with noninvasive cardiac imaging would be useful for addressing the cardiac safety profile of trastuzumab, potentially avoiding the detrimental effects of heart failure. METHODS: We used cardiac biomarkers, TVI and strain imaging, and cardiac magnetic resonance imaging to detect pre-clinical changes in LV systolic function, before conventional changes in left ventricular ejection fraction (LVEF) in human epidermal growth factor receptor II-positive breast cancer patients treated with trastuzumab in the adjuvant setting. RESULTS: Of 42 patients (mean age 47 ± 9 years) prospectively followed between 2007 and 2009, 10 (25%) developed trastuzumab-mediated cardiomyopathy (CM). Troponin T, C-reactive protein, and brain natriuretic peptide did not change over time. Within 3 months of adjuvant therapy with trastuzumab, there was a significant difference in the lateral S' between the normal cohort and the CM group (9.1 ± 1.6 cm/s and 6.4 ± 0.6 cm/s, respectively, p < 0.05). Similarly, the peak global longitudinal and radial strain decreased as early as 3 months in the trastuzumab-mediated cardiotoxicity group. As compared with both global longitudinal and radial strain, only S' was able to identify all 10 patients who developed trastuzumab-mediated CM. The LVEF subsequently decreased at 6 months of follow-up in all 10 patients, necessitating discontinuation of the drug. All 10 patients demonstrated delayed enhancement of the lateral wall of the LV within the mid-myocardial portion, consistent with trastuzumab-induced CM. CONCLUSIONS: Both TVI and strain imaging were able to detect pre-clinical changes in LV systolic function, before conventional changes in LVEF, in patients receiving trastuzumab in the adjuvant setting.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ecocardiografía Doppler/métodos , Imagen por Resonancia Cinemagnética , Disfunción Ventricular Izquierda/diagnóstico , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Biomarcadores/sangre , Neoplasias de la Mama/metabolismo , Proteína C-Reactiva/análisis , Femenino , Corazón/efectos de los fármacos , Humanos , Persona de Mediana Edad , Péptido Natriurético Encefálico/análisis , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Receptor ErbB-2/metabolismo , Medición de Riesgo/métodos , Sensibilidad y Especificidad , Trastuzumab , Troponina T/sangre , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
A high-lipid diet (HLD) may lead to adverse left ventricular (LV) remodeling and endothelial dysfunction in conditions of hemodynamic stress. Although congenital absence of nitric oxide synthase 3 (NOS3) leads to adverse LV remodeling after transverse aortic constriction (TAC), the effects of a HLD in this state remains unknown. Wild-type (WT) and NOS3 knockout mice (NOS3(-/-)) were randomized into the following 4 groups: 1) WT + low-lipid diet (LLD) (10% of energy); 2) WT + HLD (60% of energy); 3) NOS3(-/-) + LLD; and 4) NOS3(-/-) + HLD for a total of 12 wk. After 1 wk of randomization, TAC was performed on all groups. Serial echocardiography revealed a decrease in LV ejection fraction (LVEF) in WT and NOS3(-/-) mice fed the HLD compared with those fed the LLD diet at 12 wk post-TAC. Mice fed the NOS3(-/-) + HLD diet had a lower LVEF compared with mice in the other 3 groups (P < 0.05). There was greater myocyte hypertrophy, interstitial fibrosis, and percentage change in plasma cholesterol concentrations in the NOS3(-/-) + HLD group 12 wk post-TAC compared with the other 3 groups. Although high molecular weight fibroblast growth factor-2, a marker of cardiac hypertrophy, was more upregulated in the NOS3(-/-) + HLD group than in the other groups, markers of the renin-angiotensin system did not differ among them. A HLD potentiates LV dysfunction in NOS3(-/-) mice in a chronic pressure overload state.
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Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/efectos adversos , Hipertensión/complicaciones , Óxido Nítrico Sintasa de Tipo III/deficiencia , Disfunción Ventricular Izquierda/etiología , Animales , Aorta , Presión Sanguínea , Colesterol/sangre , Constricción , Ecocardiografía , Ingestión de Energía , Factor 2 de Crecimiento de Fibroblastos/análisis , Ventrículos Cardíacos/patología , Hipertrofia Ventricular Izquierda/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Peso Molecular , Células Musculares/patología , Miocardio/patología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/fisiología , Volumen Sistólico , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/patologíaRESUMEN
PURPOSE: In patients with breast cancer, the administration of doxorubicin and trastuzumab is associated with an increased risk of cardiotoxicity. Although multiple-gated acquisition (MUGA) scans and two-dimensional transthoracic echocardiography (TTE) are conventional methods for baseline and serial assessment of left ventricular ejection fraction (LVEF) in these patients, little is known about the use of real-time three-dimensional TTE (RT3D TTE) in this clinical setting. The aim of this study was to assess the accuracy of MUGA, 2D TTE, and RT3D TTE for determining LVEF in comparison to cardiac magnetic resonance imaging (CMR). METHODS: Between 2007 and 2009 inclusive, 50 female patients with human epidermal growth factor receptor 2-positive breast cancer received adjuvant trastuzumab after doxorubicin. Serial MUGA, 2D TTE, RT3D TTE, and CMR were performed at baseline, 6, and 12 months after the initiation of trastuzumab. RESULTS: A comparison of left ventricular end diastolic volume (LVEDV) demonstrated a modest correlation between 2D TTE and CMR (r = 0.64 at baseline; r = 0.69 at 12 months, respectively). A comparison of LVEDV between RT3D TTE and CMR demonstrated a stronger correlation (r = 0.87 at baseline; r = 0.95 at 12 months, respectively). Although 2D TTE demonstrated a weak correlation with CMR for LVEF assessment (r = 0.31 at baseline, r = 0.42 at 12 months, respectively), both RT3D TTE and MUGA showed a strong correlation when compared with CMR (r = 0.91 at baseline; r = 0.90 at 12 months, respectively). CONCLUSION: As compared with conventional MUGA, RT3D TTE is a feasible, accurate, and reproducible alternate imaging modality for the serial monitoring of LVEF in patients with breast cancer.
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Neoplasias de la Mama/diagnóstico por imagen , Ecocardiografía Tridimensional , Ecocardiografía , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
The increasing number of co-stimulatory molecules identified on dendritic cells (DC) to date highlights the complex regulation of co-stimulatory signals in T cell activation. We previously established a single lentiviral vector system to stably express short hairpin RNA (shRNA) to induce RNA interference (RNAi) in cell lines and primary T cells. We reasoned that the choice of shRNA target sequences in the lentiviral vector system would also allow us to regulate different levels of surface expression of a co-stimulatory molecule stably and reproducibly. In this study, we first demonstrated that lentiviral vectors delivered RNA interference in DC without functional impairments. We used CD40 as a target co-stimulatory molecule to demonstrate the feasibility of using lentiviral vectors in delivering different shRNA target sequences to genetically modify DC that expressed different levels of CD40. We provided functional data to further demonstrate that quantitative expression of CD40 on LPS-stimulated DC have different functional outcomes on Ag-specific T cell responses in vitro. Collectively, we developed a simple system that will allow us to examine functional significance(s) of the quantitative and/or qualitative expression of a single or multiple co-stimulatory molecule(s) on DC.
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Antígenos CD40/metabolismo , Células Dendríticas/metabolismo , Vectores Genéticos , Interferencia de ARN , Animales , Secuencia de Bases , Línea Celular , Proliferación Celular , Células Dendríticas/inmunología , Expresión Génica , Humanos , Interleucina-1beta/biosíntesis , Lentivirus/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Datos de Secuencia Molecular , Linfocitos T/inmunología , Transducción GenéticaRESUMEN
BACKGROUND: Trastuzumab provides considerable therapeutic benefits in the adjuvant setting of breast cancer. However, its use is limited by an elevated incidence of cardiotoxicity when used in combination with doxorubicin. Although Myocet (liposomal encapsulated doxorubicin) is less cardiotoxic, its cardiac safety profile with trastuzumab is not well known. The aim of this study was to determine if sensitive indices of left ventricular (LV) dysfunction, specifically Doppler tissue imaging (DTI), would be useful for addressing the early detection of trastuzumab and anthracycline-mediated cardiotoxicity. METHODS: In an acute murine model, wild-type C57Bl/6 mice (n = 60) received one of the following drug regimens: (1) control, (2) doxorubicin, (3) Myocet, (4) trastuzumab, (5) doxorubicin plus trastuzumab, or (6) Myocet plus trastuzumab. DTI-derived peak endocardial systolic velocity, strain rate, and LV ejection fraction were measured serially for 5 days. On day 5, the hearts, lungs, and livers were removed for histopathologic and Western blot analyses. RESULTS: Mice treated with Myocet plus trastuzumab demonstrated minimal cardiotoxicity compared with those treated with doxorubicin plus trastuzumab. Progressive LV dilatation and LV systolic dysfunction were observed by day 4 of treatment with doxorubicin plus trastuzumab, compared with preserved LV ejection fraction in the remaining groups. DTI parameters decreased within 24 hours in the doxorubicin alone and doxorubicin plus trastuzumab groups and predicted early mortality. The survival rate was only 20% at day 5 of the experiment in the doxorubicin plus trastuzumab group, whereas 100% of mice receiving trastuzumab, Myocet, or Myocet plus trastuzumab survived the 5 days. CONCLUSION: DTI can detect early LV dysfunction prior to alterations in conventional echocardiographic indices and predicts early mortality in mice receiving doxorubicin plus trastuzumab.
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Antraciclinas/efectos adversos , Anticuerpos Monoclonales/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Doxorrubicina/efectos adversos , Ecocardiografía Doppler/métodos , Diagnóstico por Imagen de Elasticidad/métodos , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/diagnóstico por imagen , Animales , Anticuerpos Monoclonales Humanizados , Antineoplásicos/efectos adversos , Relación Dosis-Respuesta a Droga , Humanos , Ratones , Ratones Endogámicos C57BL , Medición de Riesgo/métodos , Factores de Riesgo , TrastuzumabRESUMEN
BACKGROUND: Chronic rejection is a risk factor for the development of cardiac allograft vasculopathy (CAV) in heart transplant recipients. A useful animal model to study the role of immunosuppressive strategies in the prevention of chronic rejection involves heterotopic abdominal cardiac transplantation in rats. The detection of rejection and concurrent CAV traditionally involves subjective serial palpation of the graft from a scale of 0 to 4, with 4 indicating vigorous beats. Recent advances in murine echocardiography, in particular Tissue Doppler imaging (TDI), may allow for objective in vivo monitoring of chronic rejection in this transplant model. OBJECTIVE: The objective of this study was to compare the diagnostic accuracy of murine echocardiography as compared to the abdominal palpation heart score for the noninvasive detection of chronic cardiac graft rejection. METHODS: In an animal model of heterotopic cardiac transplantation, 18 male Fischer and Lewis rats were used as donors and recipients, respectively. Abdominal palpation and murine transthoracic echocardiography were performed to assess in vivo function of the transplanted heart. Left ventricular (LV) structure and function and TDI indices, including endocardial velocity (Vendo) and strain rate (SR), were evaluated in the ectopic heart. Graft tissues were processed for histological examination and graded for chronic rejection. RESULTS: Abdominal palpation scores were obtained in all 18 rats; score 1 (n = 5); score 2 (n = 4); score 3 (n = 6); and score 4 (n = 3). The mean LV ejection fraction was significantly (P <0.01) lower in score 3 and 4 grafts as compared to score 1 grafts. There was no correlation between the abdominal palpation score and LV systolic function. There was a significant relationship between decreasing Vendo or SR values and increasing grades of rejection (r = 0.65, P <0.05 and r = 0.75, P < 0.05, respectively). CONCLUSION: TDI of the transplanted heart in rats is feasible, reproducible, and more sensitive than palpation for the detection of chronic rejection.
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Ecocardiografía Doppler , Rechazo de Injerto/diagnóstico por imagen , Trasplante de Corazón/diagnóstico por imagen , Trasplante Heterotópico , Animales , Ecocardiografía Doppler/métodos , Trasplante de Corazón/inmunología , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas LewRESUMEN
Background The incidence and management of trastuzumab-mediated cardiotoxicity outside of clinical trials has not been well described. Objective and methods The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI, in a population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results Out of 152 patients (mean age 52 +/- 10 years), 36 (24%) developed trastuzumab mediated cardiomyopathy, the majority asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a pre-existing history of hypertension, smoking history, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, there was a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction (61 +/- 5% vs. 51 +/- 8%, P < 0.01). During the 6-month-followup, 34/36 patients demonstrated subepicardial linear delayed enhancement of the lateral wall of the left ventricle on cardiac MRI, suggesting trastuzumab induced myocarditis. Conclusion Approximately 1 in 4 women may develop LV systolic dysfunction after treatment with adjuvant trastuzumab, necessitating careful patient selection and close serial monitoring using noninvasive cardiac imaging.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Cardiomiopatías/inducido químicamente , Anticuerpos Monoclonales Humanizados , Quimioterapia Adyuvante/efectos adversos , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Estudios Retrospectivos , TrastuzumabRESUMEN
BACKGROUND: The most significant predictor of long-term survival in heart transplant patients is the development of accelerated cardiac allograft vasculopathy (CAV). Several studies have demonstrated the usefulness of dobutamine stress echocardiography (DSE) for screening CAV, by detecting regional wall motion abnormalities. Tissue Doppler imaging (TDI)-derived indices during DSE allow for the early detection of ischemic heart disease (IHD), prior to a reduction in regional or global systolic function. These indices include a reduction in annular systolic velocity (S'), a decrease in early diastolic annular velocity (E'), and prolongation of time to E'. In cardiac transplant patients, the application of these TDI abnormalities during DSE remains unknown. OBJECTIVE: The objective of this study was to evaluate the pattern of (TDI-derived indices of systolic and diastolic function during DSE in cardiac transplant patients without evidence of CAV. METHODS: A retrospective evaluation of 30 patients (mean age 54 +/- 11 years) who had both DSE and coronary angiography was performed. The control group consisted of 15 patients referred to rule out coronary artery disease while the study group consisted of 15 cardiac transplant patients referred for routine annual follow-up. During each stage of DSE, tissue Doppler measurements of systolic (S'), early (E'), and late (A') diastolic velocities of the lateral annulus were taken. RESULTS: All 30 patients had normal DSE based on systolic regional function and normal coronary angiograms with no stenosis >50%. There was no difference in hemodynamic parameters during the DSE at baseline and with stress. Despite normal coronaries, cardiac transplant patients demonstrated lower S', E', and A' velocities at peak stress compared to the control patients. CONCLUSION: Dobutamine-induced augmentation of TDI velocities of the lateral annulus, normally observed in the absence of ischemia in nontransplanted adults, is reduced in cardiac transplant recipients.
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Dobutamina , Ecocardiografía Doppler/métodos , Ecocardiografía de Estrés/métodos , Trasplante de Corazón , Volumen Sistólico/fisiología , Receptores de Trasplantes , Disfunción Ventricular Izquierda/diagnóstico por imagen , Aloinjertos , Cardiotónicos , Angiografía Coronaria , Femenino , Cardiopatías/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Involvement of the pericardium in meningococcal disease is a well-recognized but rare complication. Isolated meningococcal pericarditis is defined as purulent pericarditis without clinical evidence of meningococcemia. Neisseria meningitidis serotypes C, B, and W135 have been previously described to cause pericarditis. This is the 1st case report of isolated meningococcal myopericarditis due to N. meningitidis serotype Y.
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Infecciones Meningocócicas/microbiología , Neisseria meningitidis Serogrupo Y/aislamiento & purificación , Pericarditis/microbiología , Adolescente , Adulto , Antibacterianos/uso terapéutico , Cefotaxima/uso terapéutico , Preescolar , Electrocardiografía , Femenino , Humanos , Lactante , Masculino , Infecciones Meningocócicas/diagnóstico , Infecciones Meningocócicas/tratamiento farmacológico , Persona de Mediana Edad , Neisseria meningitidis Serogrupo Y/efectos de los fármacos , Penicilina G/uso terapéutico , Pericarditis/diagnóstico , Pericarditis/tratamiento farmacológico , Pericarditis/etiologíaRESUMEN
The regulation of gene expression through alternative pre-mRNA splicing is common in metazoans and is often controlled by intracellular signaling pathways that are important in cell physiology. We have shown that the alternative splicing of a number of genes is controlled by membrane depolarization and Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) through CaMKIV-responsive RNA elements (CaRRE1 and CaRRE2); however, the trans-acting factors remain unknown. Here we show that the heterogeneous nuclear ribonucleoprotein (hnRNP) L is a CaRRE1 binding factor in nuclear extracts. An hnRNP L high affinity CA (cytidine-adenosine) repeat element is sufficient to mediate CaMKIV and hnRNP L repression of splicing in a location (3'-splice site proximity)-dependent way. Depletion of hnRNP L by RNA interference followed by rescue with coexpressed exogenous hnRNP L demonstrates that hnRNP L mediates the CaMKIV-regulated splicing through CA repeats in heterologous contexts. Depletion of hnRNP L also led to increased inclusion of the stress axis-regulated exon and a CA repeat-harboring exon under depolarization or with activated CaMKIV. Moreover, hnRNP L binding to CaRRE1 was increased by CaMKIV and, conversely, was reduced by pretreatments with protein phosphatases. Therefore, hnRNP L is an essential component of CaMKIV-regulated alternative splicing through CA repeats, with its phosphorylation likely playing a critical role.
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Empalme Alternativo/fisiología , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/biosíntesis , Regulación Enzimológica de la Expresión Génica/fisiología , Ribonucleoproteína Heterogénea-Nuclear Grupo L/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/genética , Activación Enzimática/fisiología , Exones/fisiología , Células HeLa , Ribonucleoproteína Heterogénea-Nuclear Grupo L/genética , Humanos , Fosforilación/fisiología , Secuencias Repetitivas de Ácidos Nucleicos/fisiologíaRESUMEN
A 63-year-old woman with no known cardiac history presented with pulmonary edema accompanied by electrocardiographic evidence of ischemia. Echocardiography demonstrated normal cardiac dimensions, normal wall motion and mild diastolic dysfunction. Despite repeat attempts at extubation following aggressive diuresis, the patient required ongoing ventilatory support. Although cardiac catheterization revealed normal coronary arteries, computed tomography revealed a 4 cm 9 cm multinodular goiter extending into the mediastinum and compressing the trachea. A diagnosis of negative pressure pulmonary edema should be considered in the differential diagnosis of any patient presenting with acute heart failure.
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Bocio Nodular/diagnóstico por imagen , Edema Pulmonar/diagnóstico , Unidades de Cuidados Coronarios , Disnea/etiología , Electrocardiografía , Femenino , Bocio Nodular/cirugía , Insuficiencia Cardíaca/etiología , Humanos , Persona de Mediana Edad , Edema Pulmonar/cirugía , Tiroidectomía , Tomografía Computarizada por Rayos X , Estenosis Traqueal/etiología , Estenosis Traqueal/cirugíaRESUMEN
A Chiari's network, noted in approximately 2% of the general population, is a congenital remnant of the sinus venosum valve present in the right atrium. We report a case of a 67-year-old male who presented with acute infective endocarditis of the tricuspid valve due to coagulase-negative Staphylococci. Despite appropriate antimicrobial therapy for 2 weeks, the patient remained febrile with septic emboli to the pulmonary vasculature. Repeat transthoracic echocardiography (TTE) revealed persistent vegetations adherent to the tricuspid valve, extending onto the Chiari network, necessitating surgical intervention.
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Endocarditis Bacteriana/diagnóstico por imagen , Atrios Cardíacos/anomalías , Atrios Cardíacos/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Infecciones Estafilocócicas/diagnóstico por imagen , Válvula Tricúspide/diagnóstico por imagen , Anciano , Humanos , Masculino , UltrasonografíaRESUMEN
BACKGROUND: Echocardiography is widely used in the management of patients with cardiogenic shock (CS). Left ventricular ejection fraction (EF) has been shown to be an independent predictor of survival in CS. Tissue Doppler Imaging (TDI) is a sensitive echocardiographic technique that allows for the early quantitative assessment of regional left ventricular dysfunction. TDI derived indices, including systolic velocity (S'), early (E') and late (A') diastolic velocities of the lateral mitral annulus, are reduced in heart failure patients (EF < 30%) and portend a poor prognosis. In CS patients, the application of TDI prior to revascularization remains unknown. OBJECTIVE: To characterize TDI derived indices in CS patients as compared to patients with chronic CHF. METHODS: Between 2006 and 2007, 100 patients were retrospectively evaluated who underwent echocardiography for assessment of LV systolic function. This population included: Group I) 50 patients (30 males, 57 +/- 13 years) with chronic CHF as controls; and Group II) 50 patients (29 males, 58 +/- 10 years) with CS. Spectral Doppler indices including peak early (E) and late (A) transmitral velocities, E/A ratio, and E-wave deceleration time were determined. Tissue Doppler indices including S', E' and A' velocities of the lateral annulus were measured. RESULTS: Of the entire cohort, the mean LVEF was 25 +/- 5%. Cardiogenic shock patients demonstrated significantly lower lateral S', E' and a higher E/E' ratio (p < 0.01), as compared to CHF patients. The in-hospital mortality in the CHF cohort was 5% as compared to the CS group with an in hospital mortality of 40%. In the subset of CS patients (n = 30) who survived, the mean S' at presentation was higher as compared to those patients who died in hospital (3.5 +/- 0.5 vs. 1.8 +/- 0.5 cm/s). CONCLUSION: Despite similar reduction in LV systolic function, CS patients have reduced myocardial velocities and higher filling pressures using TDI, as compared to CHF patients. Whether TDI could be a reliable tool to determine CS patients with the best chance of recovery following revascularization is yet to be determined.
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Ecocardiografía Doppler/métodos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico por imagen , Choque Cardiogénico/complicaciones , Choque Cardiogénico/diagnóstico por imagen , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnóstico por imagen , Adulto , Anciano , Enfermedad Crónica , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Trastuzumab (Herceptin), an antagonist to the human epidermal growth factor 2 (HER2) receptor significantly decreases the rates of breast cancer recurrence and mortality by 50%. Despite therapeutic benefits, the risk of cardiotoxicity with trastuzumab ranges from 10-15% when administered sequentially following anthraycline chemotherapy. Little is known about the utility of cardiac magnetic resonance (CMR) in the assessment of trastuzumab mediated cardiomyopathy. METHODS AND RESULTS: Between 2005-2006 inclusive, 160 breast cancer patients were identified at a single tertiary care oncology centre. Of the total population, 10 patients (mean age 40 +/- 8 years) were identified with trastuzumab induced cardiomyopathy, based on a LVEF less than 40% on serial MUGA or echocardiography. CMR was performed in all patients to determine LV volumes, systolic function and evidence of late gadolinium enhancement (LGE). At the time of diagnosis of trastuzumab induced cardiomyopathy, the mean LVEF was 29 +/- 4%. Subepicardial linear LGE was present in the lateral portion of the left ventricles in all 10 patients. CONCLUSION: LGE-CMR is a novel way of detecting early changes in the myocardium due to trastuzumab induced cardiotoxicity.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Cardiomiopatías/inducido químicamente , Imagen por Resonancia Magnética/métodos , Adulto , Anticuerpos Monoclonales Humanizados , Medios de Contraste , Ecocardiografía , Femenino , Gadolinio DTPA , Humanos , Persona de Mediana Edad , TrastuzumabRESUMEN
We present a case of an individual who presented with acute severe mitral regurgitation in the setting of an inferior ST elevation myocardial infarction. Both transthoracic and transesophageal echocardiography demonstrated a posteriorly directed eccentric jet of severe mitral regurgitation with flail anterior mitral valve leaflet attached presumably to the anterior papillary muscle. Intraoperative findings demonstrated rupture of the postero-medial papillary muscle attached via chords to the anterior mitral valve leaflet. This case serves to remind us that both the anterior and posterior leaflets of the mitral valve are attached to both papillary muscle heads. The direction and eccentricity of the mitral regurgitant jet on echocardiography helps to locate the leaflet involved, but not necessarily the coexisting papillary muscle pathology.
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Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/etiología , Enfermedades Musculares/complicaciones , Enfermedades Musculares/diagnóstico por imagen , Músculos Papilares/diagnóstico por imagen , Enfermedad Aguda , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Rotura Espontánea/diagnóstico por imagen , UltrasonografíaRESUMEN
Pulmonic valvular stenosis represents the most frequent cause of right ventricular outflow obstruction. Transthoracic echocardiography is the imaging modality of choice in the diagnosis, evaluation and longitudinal follow-up of individuals with pulmonic stenosis (PS). Although valvular PS is usually diagnosed by two-dimensional imaging, Doppler echocardiography allows for the quantification of severity of the valvular lesion. In patients with limited acoustic windows, computed tomography and cardiac magnetic resonance imaging may provide complementary anatomical characterization of the pulmonic annulus and valve prior to percutaneous balloon valvuloplasty.
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Cateterismo , Ecocardiografía/métodos , Estenosis de la Válvula Pulmonar/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/cirugía , Adulto , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Although echocardiography has been incorporated into the diagnostic algorithm of patients with suspected infective endocarditis (IE), systematic usage in clinical practice remains ill defined. To determine the diagnostic accuracy of detecting vegetations using harmonic transthoracic echocardiography (hTTE) as compared to transesophageal echocardiography (TEE) in patients with an intermediate likelihood of native valve IE. METHODS: Between 2004 and 2005, 36 consecutive inpatients with an intermediate likelihood of disease were prospectively evaluated by hTTE and TEE. RESULTS: Of 36 patients (21 males with a mean age of 57 +/- 15 years, range 32 to 86 years), 19 patients had definite IE by TEE. The sensitivity for the detection of vegetations by hTTE was 84%, specificity of 88%, positive predictive value (PPV) of 89% and negative predictive value (NPV) of 82%. The association between hTTE and TTE interpretation for the presence and absence of vegetations were high (kappa = 0.90 and 0.85 respectively). CONCLUSION: In patients with an intermediate likelihood of native valve IE, TTE with harmonic imaging provides diagnostic quality images in the majority of cases, has excellent concordance with TEE and should be recommended as the first line test.
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Ecocardiografía/métodos , Endocarditis Bacteriana/diagnóstico por imagen , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Adulto , Anciano , Anciano de 80 o más Años , Ecocardiografía Transesofágica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
In order to establish a new more rapid, safe and sensitive colorimetric assay for the proliferation of leukemic cells, MTS/pms has been developed. This automated colorimetric assay is based on the characteristic of viable and metabolically active leukemic cells to cleave MTS/pms into a water-soluble product whose optical density is determined at 492 nm by an automated microtiter-plate reader photometer. The results indicated that only active leukemic cells cleaved MTS/pms into product measured, and dead cells did not reduce MTS/pms. A linear relations hip were found between the viable cell number and optical density of MTS/pms cleaved by HL-60 and K562 cell (r = 0.963). Compared with MTT and INT assays, the reduced product of MTS/pms is water-soluble. It is concluded that MTS/pms colorimetric assay is more rapid, accurate and sensitive for the bioassay of proliferation of leukemic cells.
Asunto(s)
Colorimetría/métodos , Leucemia/patología , Metosulfato de Metilfenazonio/metabolismo , Sales de Tetrazolio/metabolismo , Tiazoles/metabolismo , División Celular , Formazáns/metabolismo , Células HL-60 , Humanos , Células K562RESUMEN
In order to study the relationship between the expression of glutathione S-transferase (GST) in leukemic cells and the chemoresistance in patients with acute leukemia, the expressions of GST activity and GST mRNA were measured according to spectrophotometric assay based on the use of 1-choloro-2, 4-dinitro benzene and in situ hybridization. The results were studied in correlation with some clinical and pathological data. Results showed that: 1. There is no significant differences between activities of the enzyme with the different leukemia types according to the FAB classification. 2. GST activity and GST mRNA expression in the patients, both untreated and relapse, were (4.5 +/- 1.0) U, 33.3% and (7.9 +/- 15) U, 66.3% respectively. 3. In 56 patients, GST activity was 1.7 +/- 0.7, 5.9 +/- 2.0 and 9.3 +/- 1.7 U and GST mRNA expression was 13.3%, 29.7% and 76.6%, respectively, in CR, PR and NR groups. The lowest values of GST activity and GST mRNA expression were observed in those patients who achieved complete remission. The highest values of GST activity and GST mRNA expression were observed in those patients with no response to treatment. It was concluded that the expression of GST in patients with acute leukemia is closely related to the chemosensitivities clinically. Determinations of GST activity and GST mRNA are useful for predicting the chemosensitivities and the prognosis of the disease.