RESUMEN
BACKGROUND: Myocardial microRNA-133a (miR-133a) is directly related to reverse remodeling after pressure overload release in aortic stenosis patients. Herein, we assessed the significance of plasma miR-133a as an accessible biomarker with prognostic value in predicting the reversibility potential of LV hypertrophy after aortic valve replacement (AVR) in these patients. METHODS AND RESULTS: The expressions of miR-133a and its targets were measured in LV biopsies from 74 aortic stenosis patients. Circulating miR-133a was measured in peripheral and coronary sinus blood. LV mass reduction was determined echocardiographically. Myocardial and plasma levels of miR-133a correlated directly (r=0.46, P<0.001) supporting the myocardium as a relevant source of plasma miR-133a. Accordingly, a significant gradient of miR-133a was found between coronary and systemic venous blood. The preoperative plasma level of miR-133a was higher in the patients who normalized LV mass 1 year after AVR than in those exhibiting residual hypertrophy. Logistic regression analysis identified plasma miR-133a as a positive predictor of the hypertrophy reversibility after surgery. The discrimination of the model yielded an area under the receiver operator characteristic curve of 0.89 (P<0.001). Multiple linear regression analysis revealed plasma miR-133a and its myocardial target Wolf-Hirschhorn syndrome candidate 2/Negative elongation factor A as opposite predictors of the LV mass loss (g) after AVR. CONCLUSIONS: Preoperative plasma levels of miR-133a reflect their myocardial expression and predict the regression potential of LV hypertrophy after AVR. The value of this bedside information for the surgical timing, particularly in asymptomatic aortic stenosis patients, deserves confirmation in further clinical studies.
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Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Hipertrofia Ventricular Izquierda/genética , MicroARNs/sangre , Remodelación Ventricular , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/genética , Estenosis de la Válvula Aórtica/fisiopatología , Área Bajo la Curva , Femenino , Marcadores Genéticos , Humanos , Hipertrofia Ventricular Izquierda/sangre , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/fisiopatología , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Miocardio/metabolismo , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis. METHODS: In left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-ß-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 was performed in myocardial sections. RESULTS: The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-ß signaling. CONCLUSIONS: Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis.
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Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/patología , MicroARNs/sangre , Miocardio/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/metabolismo , Biomarcadores/sangre , Biomarcadores/metabolismo , Estudios de Cohortes , Femenino , Fibrosis/sangre , Fibrosis/diagnóstico , Fibrosis/metabolismo , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana EdadRESUMEN
BACKGROUND: Left ventricular (LV) reverse remodelling after valve replacement in aortic stenosis (AS) has been classically linked to the hydraulic performance of the replacement device, but myocardial status at the time of surgery has received little attention. OBJECTIVE: To establish predictors of LV mass (LVM) regression 1 year after valve replacement in a surgical cohort of patients with AS based on preoperative clinical and echocardiographic parameters and the myocardial gene expression profile at surgery. METHODS: Transcript levels of remodelling-related proteins and regulators were determined in LV intraoperative biopsies from 46 patients with AS by RT-PCR. Using multiple linear regression analysis, an equation was developed (adjusted R²=0.73; p<0.0001) that included positive [preoperative LVM, microRNA-133a, serum response factor (SRF, which is known to be a transactivator of miR-133) and age] and negative [body mass index (BMI), Wolf-Hirschhorn syndrome candidate-2 (WHSC2, which is a target for repression by miR-133a), ß-myosin heavy chain, myosin light chain-2, diabetes mellitus, and male gender] independent predictors of LVM reduction. RESULTS: Aortic valve area gain or the reduction in transvalvular gradient maintained no significant relationships with the dependent variable. Logistic regression analysis identified microRNA-133a as a significant positive predictor of LVM normalisation, whereas ß-myosin heavy chain and BMI constituted negative predictors. CONCLUSIONS: Hypertrophy regression 1 year after pressure overload release is related to the preoperative myocardial expression of remodelling-related genes, in conjunction with the patient's clinical background. In this scenario, miR-133 emerges as a key element of the reverse remodelling process. Postoperative improvement of valve haemodynamics does not predict the degree of hypertrophy regression or LVM normalisation. These results led us to reconsider the current reverse remodelling paradigm and (1) to include criteria of hypertrophy reversibility in the decision algorithm used to decide timing for the operation; and (2) to modify other prevailing factors (overweight, diabetes, etc) known to maintain LV hypertrophy.
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Estenosis de la Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Hipertrofia Ventricular Izquierda/genética , MicroARNs/análisis , Miocardio/química , Cadenas Pesadas de Miosina/genética , Cadenas Ligeras de Miosina/genética , Remodelación Ventricular/genética , Anciano , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/complicaciones , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/genética , Biopsia , Femenino , Perfilación de la Expresión Génica/métodos , Genotipo , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Prospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Factores de Riesgo , España , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaRESUMEN
BACKGROUND: The purpose of this study was to evaluate the change in renal function and its determinants after replacement of calcineurin inhibitors with a proliferation signal inhibitor (sirolimus or everolimus) in long-term heart transplant recipients. METHODS: We studied 49 consecutive patients in whom a switch to a proliferation signal inhibitor was carried out 9 ± 4 years after transplantation. Evolutive glomerular filtration rate was assessed at a mean of 28 months after conversion by the simplified MDRD equation. RESULTS: Pre-conversion glomerular filtration rate (40 ± 22 ml/min/1.73 m(2)) remained stable at 1 year after conversion (41 ± 22 ml/min/1.73 m(2)), but decreased significantly by the end of follow-up (35 ± 22 ml/min/1.73 m(2); p = 0.008 and p = 0.002 vs pre-conversion and 1-year values, respectively). In a multivariate model, including age, time from transplantation to conversion, pre-conversion glomerular filtration rate, presence of diabetes and use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy, the rate of decline in renal function was related only to the presence of diabetes (p = 0.017) and inversely related to the use of ACEI/ARB therapy (p = 0.003). There were no significant differences with respect to age, time between transplantation and replacement and baseline glomerular filtration rate. CONCLUSION: In long-term heart transplant recipients, late substitution of a calcineurin inhibitor for a proliferation signal inhibitor does not preclude a decrease in renal function in the long-term setting. We identified the presence of diabetes as the main clinical predictor of renal function deterioration. In contrast, we found that the use of ACEI/ARB therapy could exert a protective effect.
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Trasplante de Corazón/inmunología , Inmunosupresores/farmacología , Riñón/efectos de los fármacos , Riñón/fisiología , Sirolimus/análogos & derivados , Sirolimus/farmacología , Adulto , Anciano , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Calcineurina , Everolimus , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
INTRODUCTION AND OBJECTIVES: To investigate changes in the clinical characteristics, etiology and prognosis of prosthetic valve endocarditis at a tertiary-care hospital. METHODS: Retrospective cohort study of all patients diagnosed with prosthetic valve endocarditis using modified Duke criteria between 1986 and 2005. The analysis covered two time periods: January 1986 to December 1995 (P1) and January 1996 to December 2005 (P2). RESULTS: In total, 133 episodes of endocarditis occurred in 122 patients. Of these, 73 (54.9%) were diagnosed in P1 and 60 (45.1%) in P2, with incidences of 2.19% and 2.18%, respectively. The patients' mean age (SD) was 52.6+/-16.6 years in P1 and 66.2+/-11.5 years in P2 (P=.0001). Clinical characteristics were similar in the two study periods. The increase in Enterococcus infection was remarkable (12.5% in P2 vs. 4.9% in P1; relative risk [RR]=2.5; 95% confidence interval [CI], 0.7-9.6), as was the decrease in viridans group Streptococcus infection (12.5% in P2 vs. 31.1% in P1; RR=0.4; 95% CI, 0.2-0.9). Some 90.4% of patients (63/73) underwent surgery in P1, while 68.3% (41/60) underwent surgery in P2. The difference was significant (RR=0.8; 95% CI, 0.6-0.9). The in-hospital mortality rate was 28.8% in P1 and 30% in P2 (RR=1; 95% CI, 0.6-1.7). CONCLUSIONS: Changes in the epidemiology and microbiological etiology of prosthetic valve endocarditis were observed over the 20-year study period. Diagnostic and therapeutic approaches also changed, but mortality remained high.
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Endocarditis Bacteriana/etiología , Prótesis Valvulares Cardíacas/efectos adversos , Infecciones Relacionadas con Prótesis/etiología , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Introducción y objetivos. Estudiar la evolución de las características clínicas, la etiología y el pronóstico de la endocarditis sobre válvula protésica en un hospital de tercer nivel. Métodos. Estudio de cohortes retrospectivo de todos los pacientes diagnosticados de endocarditis sobre válvula protésica desde 1986 a 2005 según los criterios de Duke modificados. Se analizaron dos periodos temporales: enero de 1986 a diciembre de 1995 (P1) y enero de1996 a diciembre de 2005 (P2).Resultados. Se estudiaron 133 episodios en 122 pacientes. En 73 episodios (54,9%) la endocarditis fue diagnosticada en el P1 y en 60 (45,1%), en el P2 (incidencia del 2,19 y el 2,18% respectivamente). La edad, media ± desviación estándar, fue de 52,6 ± 16,6 años en el P1 y 66,2 ± 11,5 años en el P2 (p = 0,0001). Las características clínicas fueron similares en ambos periodos de estudio. Fue llamativo el incremento de infecciones por enterococo (el 12,5% en el P2 y el 4,9% en elP1; riesgo relativo [RR] = 2,5; intervalo de confianza [IC]del 95%, 0,7-9,6) así como el descenso de las infecciones por estreptococos del grupo viridans (el 12,5% en el P2 y el 31,1% en el P1; RR = 0,4; IC del 95%, 0,2-0,9). Los pacientes intervenidos en el P1 fueron el 90,4%(63/73), mientras que en el P2 fueron el 68,3% (41/60),diferencias que resultaron estadísticamente significativas(RR = 0,8; IC del 95%, 0,6-0,9). La mortalidad intrahospitalaria fue del 28,8% en el P1 y el 30% en el P2 (RR = 1;IC del 95%, 0,6-1,7).Conclusiones. Durante los 20 años de estudio, se ha observado un cambio en la epidemiología y la etiología microbiológica de la endocarditis sobre válvula protésica. El abordaje diagnóstico y terapéutico también se ha modificado, aunque la mortalidad se ha mantenido elevada (AU)
Introduction and objectives. To investigate changes in the clinical characteristics, etiology and prognosis of prosthetic valve endocarditis at a tertiary-care hospital. Methods. Retrospective cohort study of all patients diagnosed with prosthetic valve endocarditis using modified Duke criteria between 1986 and 2005. The analysis covered two time periods: January 1986 to December 1995 (P1) and January 1996 to December 2005 (P2).Results. In total, 133 episodes of endocarditis occurred in 122 patients. Of these, 73 (54.9%) were diagnosed in P1and 60 (45.1%) in P2, with incidences of 2.19% and 2.18%,respectively. The patients mean age (SD) was 52.6±16.6years in P1 and 66.2±11.5 years in P2 (P=.0001). Clinical characteristics were similar in the two study periods. The increase in Enterococcus infection was remarkable (12.5%in P2 vs. 4.9% in P1; relative risk [RR]=2.5; 95% confidence interval [CI], 0.7-9.6), as was the decrease in viridans group Streptococcus infection (12.5% in P2 vs. 31.1% in P1;RR=0.4; 95% CI, 0.2-0.9). Some 90.4% of patients (63/73)underwent surgery in P1, while 68.3% (41/60) underwent surgery in P2. The difference was significant (RR=0.8; 95%CI, 0.6-0.9). The in-hospital mortality rate was 28.8% in P1and 30% in P2 (RR=1; 95% CI, 0.6-1.7).Conclusions. Changes in the epidemiology and microbiological etiology of prosthetic valve endocarditis were observed over the 20-year study period. Diagnostic and therapeutic approaches also changed, but mortality remained high (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Endocarditis/epidemiología , Endocarditis/terapia , Válvula Tricúspide , Pronóstico , Factores de Riesgo , Endocarditis/clasificación , Endocarditis/complicaciones , Estudios Retrospectivos , Mortalidad HospitalariaRESUMEN
OBJECTIVE: To compare early and late outcome of patients with prosthetic valve endocarditis treated medically versus surgically and to determine predictors of in-hospital death. We retrospectively reviewed patient's clinical records, including laboratory findings, surgery, and pathologic files, in an acute-care, 1200-bed teaching hospital. METHODS: One hundred thirty-three episodes of definite prosthetic valve endocarditis as defined by the Duke University diagnostic criteria occurred in 122 patients from January 1986 to December 2005. Logistic regression model was used to identify prognostic factors of in-hospital mortality. Long-term follow-up was made to assess late prognosis. RESULTS: Bioprostheses were involved in 52% of cases and mechanical valves in 48%. The aortic valve was affected in 45% of patients. Staphylococcus epidermidis was isolated in 23% of cases, Streptococcus spp in 21%, S aureus in 13%, and Enterococcus in 8%. Cultures were negative in 18% of cases. Twenty-six patients were treated medically and 107 with combined antibiotics and valve replacement. The operative mortality was 6.5% and the in-hospital mortality, 29%. Presence of an abscess at echocardiography, urgent surgical treatment, heart failure, thrombocytopenia, and renal failure were significant predictors of in-hospital death. Kaplan-Meier survival at 12 months was 42% in patients treated medically and 71% in those treated surgically (P = .0007). Freedom from endocarditis was 91% at the end of follow-up. CONCLUSIONS: Prosthetic valve endocarditis is a serious condition with high mortality. Patients with perivalvular abscess had a worse prognosis, and combined surgical and medical treatment could be the preferred approach to improve outcome.
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Endocarditis/mortalidad , Prótesis Valvulares Cardíacas/microbiología , Endocarditis/tratamiento farmacológico , Endocarditis/cirugía , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: TGF-beta1 is involved in cardiac remodeling through an auto/paracrine mechanism. The contribution of TGF-beta1 from plasmatic source to pressure overload myocardial remodeling has not been analyzed. We investigated, in patients with valvular aortic stenosis (AS), and in mice subjected to transverse aortic arch constriction (TAC), whether plasma TGF-beta1 relates with myocardial remodeling, reflected by LV transcriptional adaptations of genes linked to myocardial hypertrophy and fibrosis, and by heart morphology and function. METHODOLOGY/PRINCIPAL FINDINGS: The subjects of the study were: 39 patients operated of AS; 27 healthy volunteers; 12 mice subjected to TAC; and 6 mice sham-operated. Myocardial samples were subjected to quantitative PCR. Plasma TGF-beta1 was determined by ELISA. Under pressure overload, TGF-beta1 plasma levels were significantly increased both in AS patients and TAC mice. In AS patients, plasma TGF-beta1 correlated directly with aortic transvalvular gradients and LV mass surrogate variables, both preoperatively and 1 year after surgery. Plasma TGF-beta1 correlated positively with the myocardial expression of genes encoding extracellular matrix (collagens I and III, fibronectin) and sarcomeric (myosin light chain-2, beta-myosin heavy chain) remodelling targets of TGF-beta1, in TAC mice and in AS patients. CONCLUSIONS/SIGNIFICANCE: A circulating TGF-beta1-mediated mechanism is involved, in both mice and humans, in the excessive deposition of ECM elements and hypertrophic growth of cardiomyocytes under pressure overload. The possible value of plasma TGF-beta1 as a marker reflecting preoperative myocardial remodeling status in AS patients deserves further analysis in larger patient cohorts.
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Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/fisiopatología , Factor de Crecimiento Transformador beta1/sangre , Remodelación Ventricular/fisiología , Anciano , Animales , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Cardiomegalia/sangre , Cardiomegalia/complicaciones , Cardiomegalia/diagnóstico por imagen , Estudios de Casos y Controles , Demografía , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Regulación de la Expresión Génica , Prótesis Valvulares Cardíacas , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Ratones , Miocardio/metabolismo , Miocardio/patología , Tamaño de los Órganos , Cuidados Posoperatorios , Cuidados Preoperatorios , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sarcómeros/metabolismo , Transducción de Señal/genética , Ultrasonografía , Remodelación Ventricular/genéticaRESUMEN
Pulmonary venous vascular complications after lung transplantation are rare and a major cause of morbidity and mortality unless diagnosed and treated early. The epidemiological, diagnostic, and management characteristics of 33 patients (two of them in our hospital) with post-transplant pulmonary vein obstruction published in the literature were reviewed. We consider of utmost importance to differentiate stenosis from thrombosis as the cause of the obstruction. The angiography, considered the gold standard for diagnosis, was replaced by transesophageal echocardiography (TEE) in 79% of the cases, but no echocardiographic diagnostic criteria were defined. A diameter of the pulmonary veins, with 2D/color TEE, <0.5 cm, peak systolic flow velocity (PSFV) >1 m/s, pulmonary vein-left atrial pressure gradient (PVLAG) >/=10-12 mmHg, non-permeable flow through the stenosis and the presence of thrombus at that level, must lead us to suspect this complication. Higher mortality rates were found in unilateral procedures and in women. We consider that TEE must be carried out as part of the intraoperative routine or within the first 24 h of the post-operative period.
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Ecocardiografía Transesofágica/métodos , Trasplante de Pulmón/efectos adversos , Fibrosis Pulmonar/cirugía , Enfermedad Veno-Oclusiva Pulmonar/diagnóstico por imagen , Anciano , Diagnóstico Diferencial , Resultado Fatal , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Enfermedad Veno-Oclusiva Pulmonar/etiologíaRESUMEN
Gender influence on left ventricular (LV) remodeling associated to aortic valve stenosis (AS) has been long recognized, but underlying myocardial gene expression patterns have not been explored. We studied whether sex differences in echocardiographic LV anatomy and function in AS patients are associated with specific changes in myocardial mRNA expression of remodeling proteins. AS (n=39) and control (n=23)patients were assessed echocardiographically, and LV myocardial mRNA levels were quantified by PCR. AS patients exhibit increased wall thicknesses and LV mass index (LVMI), but only men show chamber dilation.Collagens and fibronectin mRNA levels increased correlatively to transforming growth factor-beta1 (TGF-beta1). In AS women, collagen I upregulation was proportionally higher than other extracellular matrix (ECM)components. No changes in matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 were detected. Gene expressions of sarcomeric proteins (beta-myosin heavy chain and myosin light chain-2) and TGF-beta1 were directly correlated with each other. Myosin light chain-2 mRNA levels increased proportionally to the transvalvular gradient, but women did so in a greater extent than men for a given gradient. In women, the hypertrophic growth response, reflected by LVMI, was proportional to the expression of genes encoding sarcomeric proteins and TGF-beta1. In men, chamber dilation and deterioration of LVEF was proportional to collagens, fibronectin, and TGF-beta1 gene expression levels. We evidenced gender biased gene expression patterns of the intracellular TGF-beta pathways involving the Smad branch, but not the TAK-1 branch, that could contribute to the remodeling differences observed in AS men and women. Based on these findings, a gender specific therapeutic approach of pressure overload LV hypertrophy could be justified.
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Expresión Génica , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/metabolismo , Anciano , Estudios de Casos y Controles , Ecocardiografía , Femenino , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , ARN Mensajero/metabolismo , Factores Sexuales , Factor de Crecimiento Transformador beta/metabolismo , Remodelación VentricularRESUMEN
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Humanos , Sistema de Conducción Cardíaco/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico , Obstrucción del Flujo Ventricular Externo/diagnóstico , ElectrocardiografíaRESUMEN
BACKGROUND: This study describes our experience with proliferation signal inhibitors in de novo heart transplant recipients with significant renal impairment. To circumvent further nephrotoxicity, calcineurin inhibitors were avoided in the peri-operative period. METHODS: Immunosuppression in 20 patients was with a proliferation signal inhibitor (sirolimus, 14; everolimus, 6), an anti-mitotic drug, and corticosteroids from the time of transplantation. Induction was used in 9 patients (45%). All patients had preoperative significant renal dysfunction (mean glomerular filtration rate <30 ml/min/1.73 m(2)), and 4 patients required dialysis. RESULTS: Post-operatively, the glomerular filtration rate significantly increased (>65 ml/min/1.73 m(2) at Month 1, remaining stable thereafter). No patients required dialysis after the first month of transplantation. Mean follow-up was 500 days. Rejection episodes occurred in 11 patients (55%), and 4 patients died (2 of rejection, although 1 death occurred 48 days after conversion to conventional treatment with tacrolimus). Half of the patients were eventually converted to conventional calcineurin-inhibitor therapy because of proliferation signal inhibitor adverse events. CONCLUSION: Although this immunosuppressive approach was associated with a somewhat high rate of rejection and frequent side effects, it represents an attractive alternative in the complicated peri-operative setting of patients with significant renal impairment. This approach could serve as a temporary bridge to a conventional treatment.
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Inhibidores de la Calcineurina , Trasplante de Corazón/efectos adversos , Inmunosupresores/uso terapéutico , Insuficiencia Renal/epidemiología , Administración Oral , Corticoesteroides/uso terapéutico , Azatioprina/uso terapéutico , División Celular/efectos de los fármacos , Everolimus , Tasa de Filtración Glomerular , Rechazo de Injerto/prevención & control , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Pruebas de Función Renal , Estudios Retrospectivos , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados , Sirolimus/uso terapéuticoRESUMEN
Pulmonary toxicity (PT) is emerging as a frequent and serious complication of sirolimus, a proliferation signal inhibitor (PSI) used in solid-organ transplantation. Everolimus is a more recently developed PSI with molecular structure very similar to that of sirolimus. Surprisingly, although experience with everolimus is increasing and becoming substantial, there remains very little information about everolimus-related PT. Herein we report 2 heart transplant recipients who developed a non-infectious pulmonary syndrome after everolimus treatment was started. Transbronchial pulmonary biopsy specimens showed typical interstitial pneumonitis, and everolimus discontinuation resulted in rapid clinical and radiological improvement. Although PT seems to be more common after sirolimus exposure, everolimus is by no means spared from this potentially lethal complication and should always be suspected in the relevant clinical setting.
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Trasplante de Corazón , Inmunosupresores/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Pulmón/patología , Sirolimus/análogos & derivados , Anciano , Biopsia , Everolimus , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Sirolimus/efectos adversos , Resultado del TratamientoRESUMEN
INTRODUCTION AND OBJECTIVES: It is vital that obstruction of the left main coronary artery (LMCA) is diagnosed early. We investigated the value of ST-segment and QRS-complex vector analysis in identifying LMCA obstruction in acute coronary syndrome. METHODS: The study involved 57 consecutive patients with electrocardiographic features suggestive of LMCA obstruction. Both ST-segment and QRS-complex parameter vectors were analyzed. RESULTS: Coronary angiography showed that the obstructed vessel was the LMCA in 20 patients, the left circumflex artery in 19, the right coronary artery in 10, and the left anterior descending artery in three. Five patients had three-vessel disease. An ST vector that was directed between -90 degrees and 180 degrees in the frontal plane was observed in 100% of patients with an LMCA obstruction (P< .001). The specificity of this observation was 78%. An ST vector directed anteriorly or parallel to the horizontal plane was present in 95% of patients (19/20) with an LMCA obstruction (P< .001; specificity 92%). A QRS vector with a left shift é-30 degrees was observed in 75% (15/20) with LMCA disease (P< .001; specificity 95%). An ST vector directed between -90 degrees and 180 degrees and anteriorly had a sensitivity of 95% and specificity of 100% for LMCA obstruction. An ST vector directed between -90 degrees and 180 degrees combined with a left QRS vector shift > or =-30 degrees had a sensitivity of 75% and a specificity of 100% for LMCA obstruction. A simple algorithm combining these observation was able to predict LMCA obstruction in 100% of patients. CONCLUSIONS: In acute coronary syndrome, ST-segment and QRS-complex vector analysis can predict the presence of LMCA obstruction.
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Estenosis Coronaria/diagnóstico , Electrocardiografía , Adulto , Anciano , Anciano de 80 o más Años , Estenosis Coronaria/fisiopatología , Electrocardiografía/métodos , Electrofisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Introducción y objetivos. El diagnóstico precoz de la obstrucción del tronco coronario izquierdo es crucial. Analizamos el valor del análisis vectorial del segmento ST y el QRS en la obstrucción del tronco izquierdo en el síndrome coronario agudo. Métodos. Estudiamos criterios vectoriales válidos en 57 pacientes consecutivos con electrocardiogramas compatibles con obstrucción del tronco izquierdo. Resultados. La coronariografía mostró obstrucción del tronco coronario izquierdo en 20 pacientes, circunfleja en 19, coronaria derecha en 10, triple vaso en 5 y descendente anterior en 3. El vector del ST dirigido entre 90° y 180° en el plano frontal se observó en el 100% de los pacientes con afección del tronco coronario izquierdo (p < 0,001) con un 78% de especificidad. El vector del ST anterior o paralelo en el plano horizontal se observó en el 95% (19/20) de los pacientes con afección del tronco izquierdo (p < 0,001) con un 92% de especificidad. El vector del QRS con desviación a la izquierda é 30° se observó en el 75% (15/20) de los pacientes con afección del tronco izquierdo (p < 0,001) con un 95% de especificidad. Un vector ST entre 90° y 180° y anterior mostró un 95% de sensibilidad y un 100% de especificidad para la obstrucción del tronco izquierdo. Un vector ST entre 90 y 180° con un QRS con desviación a la izquierda é 30° mostró un 75% de sensibilidad y un 100% de especificidad de obstrucción del tronco izquierdo. Un sencillo algoritmo predice la obstrucción del tronco coronario izquierdo en el 100% de los pacientes. Conclusiones. En el síndrome coronario agudo, el análisis vectorial del segmento ST y el QRS predice la obstrucción del tronco coronario izquierdo (AU)
Introduction and objectives. It is vital that obstruction of the left main coronary artery (LMCA) is diagnosed early. We investigated the value of ST-segment and QRS-complex vector analysis in identifying LMCA obstruction in acute coronary syndrome. Methods. The study involved 57 consecutive patients with electrocardiographic features suggestive of LMCA obstruction. Both ST-segment and QRS-complex parameter vectors were analyzed. Results. Coronary angiography showed that the obstructed vessel was the LMCA in 20 patients, the left circumflex artery in 19, the right coronary artery in 10, and the left anterior descending artery in three. Five patients had three-vessel disease. An ST vector that was directed between 90° and 180° in the frontal plane was observed in 100% of patients with an LMCA obstruction (P<.001). The specificity of this observation was 78%. An ST vector directed anteriorly or parallel to the horizontal plane was present in 95% of patients (19/20) with an LMCA obstruction (P<.001; specificity 92%). A QRS vector with a left shift é30° was observed in 75% (15/20) with LMCA disease (P<.001; specificity 95%). An ST vector directed between 90° and 180° and anteriorly had a sensitivity of 95% and specificity of 100% for LMCA obstruction. An ST vector directed between 90° and 180° combined with a left QRS vector shift ≥30° had a sensitivity of 75% and a specificity of 100% for LMCA obstruction. A simple algorithm combining these observation was able to predict LMCA obstruction in 100% of patients. Conclusions. In acute coronary syndrome, ST-segment and QRS-complex vector analysis can predict the presence of LMCA obstruction (AU)
Asunto(s)
Humanos , Estenosis Coronaria/diagnóstico , Electrocardiografía/métodos , Enfermedad Coronaria/diagnóstico , Tronco Arterial/fisiopatología , Diagnóstico Precoz , Enfermedad Coronaria/fisiopatología , Bloqueo Cardíaco/fisiopatología , Angiografía Coronaria , ElectrocardiografíaRESUMEN
BACKGROUND: The existence of a diabetic cardiomyopathy has been recently supported by epidemiological studies. Increased oxidative stress and myocardial fibrosis has been hypothesized as etiopathogenic mechanisms. We sought to demonstrate the existence of incipient myocardial dysfunction in type 2 diabetes and its relation with markers of oxidative stress and myocardial fibrosis. METHODS: We studied by echocardiography 25 uncomplicated type 2 diabetic patients and 12 sex- and age-matched control subjects. Stress-corrected endocardial and midwall shortening and systolic and early diastolic velocity of the lateral mitral annulus (Doppler tissue) were used as parameters of myocardial function. Serum levels of glutathione peroxidase and procollagen type I carboxy-terminal peptide were used as markers of oxidative stress and myocardial fibrosis, respectively. RESULTS: Diabetics had significant lower values of corrected endocardial shortening than control subjects (P = 0.029). Both systolic and early diastolic mitral annulus velocities were significantly reduced in diabetics as compared to control subjects (P = 0.008 and P = 0.003, respectively). In diabetic patients, corrected endocardial (r = -0.56) and midwall shortening (r = -0.38) correlated with procollagen type I carboxy-terminal peptide, whereas systolic and early diastolic velocities of the mitral annulus correlated with glutathione peroxidase (both r = 0.44). CONCLUSIONS: In a highly selected group of uncomplicated type 2 diabetic patients, we found evidence of systolic and diastolic myocardial dysfunction, especially with the use of pulsed Doppler tissue imaging. The correlations between parameters of myocardial function and glutathione peroxidase and procollagen type I carboxy-terminal peptide support a mechanistic role for the increased oxidative stress and myocardial fibrosis in the myocardial dysfunction of type 2 diabetes.
Asunto(s)
Cardiomiopatías/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Estrés Oxidativo , Disfunción Ventricular Izquierda/metabolismo , Cardiomiopatías/sangre , Cardiomiopatías/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Fibrosis/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Disfunción Ventricular Izquierda/sangreRESUMEN
We report an asymptomatic 8-year-old girl with anomalous pulmonary venous connection to the IVC and systemic arterial supply (scimitar syndrome). We present for the first time a description of gadolinium-enhanced 3D MR angiography that provided concurrent non-invasive complete anatomical (arterial and venous supply) and 'functional' (calculation of left-to-right shunt using phase-contrast-MRI performed in the ascending aorta, main pulmonary artery and anomalous pulmonary vein) diagnosis, avoiding the need for more traditional invasive techniques. As the shunt quantification was less than 2:1, conservative management was decided upon.
Asunto(s)
Angiografía por Resonancia Magnética , Imagen por Resonancia Cinemagnética , Síndrome de Cimitarra/diagnóstico , Niño , Medios de Contraste , Femenino , Gadolinio DTPA , Humanos , Imagenología Tridimensional , Síndrome de Cimitarra/patologíaRESUMEN
Presentamos el caso de un paciente de 44 años al que se realizó trasplante cardíaco ortotópico, por ser portador de miocardiopatía dilatada idiopática con hipertensión arterial pulmonar y resistencias arteriolares elevadas. Al salir de cirugía extracorpórea tras el trasplante sufrió una hipoxia grave, secundaria a un foramen oval permeable. Éste nunca había dado problemas en el donante, pero al someterlo a la situación hemodinámica especial de nuestro paciente, con presiones elevadas en el lado derecho, se abrió ocasionando un shunt derecha-izquierda significativo que provocó la hipoxia grave del receptor. Se realizó cierre quirúrgico del foramen oval (AU)