Josefa González

Matrix metalloproteinases and tissue remodeling in hypertrophic cardiomyopathy.

BACKGROUND Hypertrophic cardiomyopathy (HCM) is defined by the presence of unexplained left ventricular hypertrophy, myocyte disarray, and interstitial fibrosis. An increase in extracellular matrix produces interstitial fibrosis, by raised amounts of collagen type I/III. Regions of myocardial late gadolinium enhancement by cardiac magnetic resonance (CMR) represented increased myocardial collagen. Regarding the role of matrix metalloproteinases (MMPs) in myocardial remodeling and subsequent fibrosis, the aim of our study was to explore the relation between MMP system and myocardial late gadolinium enhancement by CMR (as expression of image-documented fibrosis) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (as a marker of cardiac overload) in HCM. METHODS We included 67 HCM patients (44 men aged 49 +/- 14 years) and were compared to 58 controls with similar age and sex. Risk factors for sudden death were recorded. A blinded CMR was performed with gadolinium. Matrix metalloproteinase 1, MMP-2, and MMP-9 plasma levels were assayed by enzyme-linked immunosorbent assay. Serum samples were used for measurement of NT-proBNP. RESULTS In patients, >50% of MMP-1 values were below the lowest limit of detection of the technique. Raised levels of MMP-2, MMP-9, and NT-proBNP were observed in HCM patients (all P < .01). Matrix metalloproteinase 2 was associated with dyspnea (P = .049) and correlated with MMP-9 (r = 0.28, P = .025) and NT-proBNP (r = 0.39, P = .001). Matrix metalloproteinase 9 was associated with the presence of gadolinium enhancement in CMR (P = .001) and correlated with NT-proBNP (r = 0.52, P < .001). NT-proBNP was also associated with gadolinium enhancement (P = .006). Both MMP-2 and MMP-9 correlated negatively with exercise capacity (metabolic equivalent units), (r = -0.36 and r = -0.42 respectively, both P < .01). On multivariate analysis (adjusted by sudden death risk factors and echocardiographic markers), only MMP-9 was associated with fibrosis (P = .011). CONCLUSIONS Matrix metalloproteinase 9 is independently associated with gadolinium enhancement on CMR in patients with hypertrophic cardiomyopathy, suggesting that the MMP system has an important role in cardiac remodeling and fibrosis in this condition.

Real-time three-dimensional transoesophageal echocardiography in the assessment of aortic valve stenosis

AIMS To determine the feasibility of real-time three-dimensional transoesophageal echocardiography (3D-TOE) in the evaluation of aortic valve stenosis, to study its reliability, and to test the concordance of this new method when compared with transthoracic two-dimensional echocardiography (2D-TTE) as the diagnostic standard. METHODS AND RESULTS Fifty-nine consecutive patients with moderate-to-severe aortic valve stenosis were assessed by means of 2D-TTE and 3D-TOE by independent blinded observers. Aortic valve planimetry was possible in 94.9% of patients. Inter-observer intraclass correlation coefficients (ICC) were 0.892 (CI 95% 0.818-0.936; P < 0.001), and 0.871 (CI 95% 0.780-0.925; P < 0.001) for 2D-TTE and 3D-TOE, respectively. Bland-Altman plot showed a mean difference in aortic valve area (AVA) of 0.040 cm(2), with 2D-TTE yielding larger values than 3D-TOE. ICC of both methods was 0.724 (CI 95% 0.530-0.839; P < 0.001). CONCLUSION Assessment of AVA by means of 3D-TOE is feasible in most patients with aortic valve stenosis. Reliability of the measurement is good. However, there is some disagreement with standard 2D-TTE that needs further investigation.

Variables associated with contrast-enhanced cardiovascular magnetic resonance in hypertrophic cardiomyopathy: clinical implications.

BACKGROUND Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and disarray. Late gadolinium enhancement in cardiovascular magnetic resonance (CMR) is observed in regions of increased myocardial collagen. The extent of late gadolinium enhancement has been associated with higher prevalence of risk factors of sudden death. The aim of the present study was to describe the clinical characteristics and the presence of risk factors for sudden death in a series of patients from 2 referral centers for HCM in relation to late gadolinium enhancement in CMR. METHODS AND RESULTS A total of 120 patients (47 +/- 16 years) were included. All patients fulfilled conventional criteria for HCM. A complete history and clinical examination were performed. Risk factors for sudden death were evaluated. A blinded CMR was performed with late gadolinium enhancement in the left ventricular short-axis orientation. NT pro B-type natriuretic protein (BNP) and C-reactive protein were determined in serum samples. A total of 83 patients (69%) showed late gadolinium enhancement. These patients had higher maximal left ventricular wall thickness (22 +/- 5 versus 17 +/- 3 mm, P < .001), showed more frequently obstruction (42% versus 16%, P = .006), nonsustained ventricular tachycardia (38% versus 8%, P = .001), worse exercise capacity (8 +/- 4 versus 10 +/- 4 METs, P = .003) and increased levels of NT BNP (656 [300-1948] versus 290 [122-948] pg/mL, P = .020). On multivariate analysis, maximal left ventricular wall thickness (P < .001) and nonsustained ventricular tachycardia (P = .011) remained associated with gadolinium-enhanced imaging. Number of risk factors for sudden death was associated with late gadolinium enhancement (OR 2.18, 95%CI 1.45-3.20, P < .001). CONCLUSIONS Late gadolinium enhancement in CMR is a common finding in HCM. Increased maximal left ventricular wall thickness and nonsustained ventricular tachycardia are associated with late gadolinium enhancement. Associations with risk factors for sudden death and functional status are observed.

Proyecto de un plan de accesibilidad al intervencionismo coronario en el infarto agudo de miocardio en la Región de Murcia (España). Registro APRIMUR

Introduccion y objetivos La Region de Murcia posee las caracteristicas geograficas y la infraestructura suficiente para asegurar el empleo de la angioplastia coronaria en el infarto agudo de miocardio en los casos indicados segun las vigentes guias de actuacion. La elaboracion de un plan regional de intervencionismo coronario en el infarto agudo de miocardio podria aumentar el numero de pacientes beneficiados del tratamiento de reperfusion en general, y de la angioplastia primaria en particular. Material y metodos El plan iniciado en abril de 2000 consta de 4 fases: 1) establecimiento de la angioplastia primaria como tratamiento de eleccion en el infarto en el hospital de referencia regional; 2) extension de la fase 1 a un segundo hospital distante 10 km del hospital de referencia; 3) extension de la fase 1 a toda la capital, y 4) facilitacion al resto de la region de la angioplastia coronaria en el infarto agudo de miocardio. Resultados Entre enero de 2000 y agosto de 2001 se han realizado 392 angioplastias en el seno del infarto agudo de miocardio. El 92 y el 85% de los pacientes con indicacion de tratamiento de reperfusion recibieron angioplastia primaria en los hospitales implicados en las fases 1 y 2, respectivamente, con una mediana de retraso (indicacion-inicio de angioplastia primaria) de 25 y 35 min, respectivamente. La mortalidad total fue del 11,5% (5,2% en los pacientes sin shock al ingreso). Conclusiones La elaboracion de un plan regional y la utilizacion de la angioplastia primaria pueden aumentar el numero de pacientes que reciba tratamiento de reperfusion, aproximandose a las actuales recomendaciones terapeuticas en el infarto agudo de miocardio.

Intervalos de tiempo transcurridos en la realización de la angioplastia primaria: desde el inicio de los síntomas hasta la restauración del flujo

Introduccion y objetivo Una limitacion para el empleo generalizado de la angioplastia primaria es el retraso al que puede asociarse. La mayoria de los datos actuales procede de ensayos clinicos y existen pocos conocimientos respecto a su aplicacion en la practica clinica habitual. El objetivo del estudio fue analizar los tiempos invertidos en cada etapa en la realizacion de una angioplastia primaria en un hospital donde es el tratamiento de reperfusion de eleccion en el infarto agudo de miocardio. Pacientes y metodo Estudio prospectivo observacional de los pacientes con infarto agudo de miocardio ingresados en nuestro centro e indicacion de tratamiento de reperfusion entre abril de 2000 y agosto de 2001. Se analizan los tiempos parciales desde el inicio de los sintomas hasta la finalizacion de la angioplastia. Resultados Se realizo angioplastia primaria a 201 de los 218 pacientes con indicacion de tratamiento de reperfusion (92%). La medianas (percentiles 25–75) fueron: tiempo 1 (inicio de sintomas-llegada hospital): 91 min (rango, 50–150); tiempo 2 (llegada al hospital-llamada a equipo de hemodinamica): 20 min (rango, 10–49); tiempo 3 (llamada al equipo de hemodinamica-llegada equipo): 15 min (rango, 0–20); tiempo 4 (llegada equipo-llegada del paciente al laboratorio): 10 min (rango, 5–15); tiempo 5 (llegada pacienteapertura arteria responsable): 20 min (rango, 15–30); tiempo 6 (apertura arteria-flujo TIMI III): 10 min (rango, 0–25). Conclusiones El tiempo mas prolongado en la realizacion de la angioplastia primaria transcurre desde el inicio de los sintomas hasta la llegada al hospital. Dentro del hospital son el diagnostico y la decision de realizar la angiopastia lo que motiva el mayor tiempo. Es posible generalizar la realizacion de la angioplastia primaria con tiempos claramente inferiores a los recomendados en las actuales guias de actuacion.

Aplicación de una puntuación de riesgo coronario (TIMI Risk Score) en una población no seleccionada de pacientes que consultan por dolor torácico en un servicio de urgencias

Introduccion y objetivos Diferentes algoritmos de estratificacion del sindrome coronario agudo (SCA) permiten identificar a los individuos con un mayor riesgo que pueden beneficiarse de tratamientos mas agresivos. Se ha demostrado que el TIMI Risk Score (TRS) es util en pacientes con un riesgo intermedio y alto, pero faltan evidencias acerca de su aplicabilidad clinica en pacientes no seleccionados. El objetivo es comprobar la eficacia del TRS en la estratificacion del riesgo en una poblacion con dolor toracico no seleccionada. Pacientes y metodo Se incluyo a 1.254 pacientes consecutivos que acudieron a urgencias por dolor toracico no traumatico sin ascenso del segmento ST (edad 54 ± 19 anos, 57% varones). Se ingreso a 343 (27%) y se dio de alta a 911 (73%). Se registro la aparicion de eventos cardiacos a los 6 meses. Resultados En el grupo dado de alta desde urgencias, 45 (5,3%) pacientes fueron ingresados durante el seguimiento, 9 (1,1%) recibieron tratamiento de revascularizacion, 5 (0,6%) presentaron un infarto agudo miocardico (IAM) y 2 (0,2%) fallecieron por causa cardiovascular. Los que obtuvieron una mayor puntuacion en el TRS presentaron mas riesgo de presentar el evento combinado muerte, infarto o revascularizacion (riesgo relativo por incremento de unidad = 3,63; intervalo de confianza [IC] del 95%, 2,20-6,00; p Conclusiones El TRS es una herramienta eficaz para la estratificacion pronostica de pacientes no seleccionados que consultan por dolor toracico. Permite identificar a los individuos de alto riesgo que se beneficiarian de ingreso hospitalario y tratamiento agresivo precoz.

Left atrial remodelling in hypertrophic cardiomyopathy: relation with exercise capacity and biochemical markers of tissue strain and remodelling.

Background:  Left atrial remodelling, assessed as left atrial volume (LAV), has been proposed as a good marker of left ventricular diastolic dysfunction. The aim of this study was to analyse the influence of LAV on exercise performance in hypertrophic cardiomyopathy (HCM), and in a subset of subjects, assess the relation of LAV and exercise performance to four biomarkers of disease pathophysiology: matrix metalloproteinase‐2 (MMP‐2) and tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) (as indices of tissue remodelling), N‐terminal portion of pro B‐type natriuretic peptide (NT‐pro‐BNP) (associated with ventricular dysfunction) and C‐reactive protein (CRP, an index of inflammation).

Prognostic value of two polymorphisms in non-sarcomeric genes for the development of atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment. AIM We tested the hypothesis that 2 non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] are associated with the development of AF. DESIGN Prospective study. METHODS Two polymorphisms in non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] were analysed in 159 HCM patients (49.3 ± 14.9 years, 70.6% male) and 136 controls. All subjects were clinically stable and in sinus rhythm at entry in the study, without ischemic heart disease or other significant co-morbidities that could mask the effect of the analysed polymorphisms (i.e. previous AF). Thirty-nine patients (24.4%) developed AF during a median follow-up of 49.5 months. RESULTS Patients with the -344T>C polymorphism in CYP11B2 gene had a higher risk for AF development [HR: 3.31 (95% CI 1.29-8.50); P = 0.008]. In a multivariate analysis, the presence of the C allele in CYP11B2 gene [HR: 3.02 (1.01-8.99); P = 0.047], previous AF [HR: 2.81 (1.09-7.23); P = 0.033] and a left atrial diameter of ≥42 mm [HR: 2.69 (1.01-7.18); P = 0.048] were independent predictors of AF development. The presence of the polymorphic allele was associated with higher aldosterone serum levels. CONCLUSION We have shown for the first time that the CYP11B2 polymorphism is an independent predictor for AF development in HCM patients. This highlights the importance of non-sarcomeric genes in the phenotypic heterogeneity of HCM. The association with higher aldosterone serum levels could relate to greater fibrosis and cardiac remodelling.

Tetralogía de Fallot en el adulto complicada con hemoptisis grave. Tratamiento mediante embolización de la arteria tirocervical izquierda

La tetralogia de Fallot con atresia pulmonar constituye una situacion especial en la que se permite la supervivencia hasta la edad adulta. En estos casos se desarrollan complicaciones, como la hemoptisis, que comprometen la vida del paciente y tienen dificil tratamiento. Cuando la causa del sangrado es la rotura de cortocircuitos arteriovenosos, frecuentes en las malformaciones vasculares multiples que se originan en esta cardiopatia, la embolizacion selectiva de estas malformaciones puede ser una opcion eficaz de tratamiento.

[Use of a coronary risk score (the TIMI Risk Score) in a non-selected patient population assessed for chest pain at an emergency department].

INTRODUCTION AND OBJECTIVES Stratification algorithms for acute coronary syndrome enable the identification of high-risk patients who will benefit from more aggressive treatment. The TIMI Risk Score (TRS) has been shown to be useful in intermediate- and high-risk patients. However, little is known about its value in non-selected patients. Our aim was to assess the efficacy of the TRS for risk stratification in a non-selected population with chest pain. PATIENTS AND METHOD We evaluated 1254 consecutive patients (age, 54 [19] years; 57% male) attending an emergency department for chest pain. Overall, 343 (27%) were admitted and 911 (73%) were discharged. All cardiac events during 6-month follow-up were recorded. RESULTS Of the 911 discharged patients, 45 (5.3%) were admitted during follow-up: 9 (1.1%) underwent revascularization, 5 (0.6%) had a myocardial infarction (MI), and 2 (0.2%) died from cardiovascular disease. Patients with a high TRS had a significantly higher risk of reaching the composite endpoint of death, MI, or revascularization (relative risk per unit of TRS increase, 3.63; 95% CI, 2.20-6.00; P < .001). Of the patients who were initially admitted, 22 (6.4%) underwent revascularization, 4 (1.2%) had an MI, and 14 died (4.1%) from cardiovascular disease during follow-up. The relative risk of the composite endpoint per unit of TRS increase was 1.72 (95% CI, 1.32-2.24; P < .001). CONCLUSIONS The TIMI risk score is useful for stratifying cardiovascular event risk in non-selected patients with chest pain. The score can identify high-risk patients who will benefit from hospital admission and early aggressive treatment.