Publications (13)55.58 Total impact
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Article: Cardiotrophin-1 plasma levels are associated with the severity of hypertrophy in hypertrophic cardiomyopathy.
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ABSTRACT: Cardiotrophin-1 (CT-1) is a cytokine that induces hypertrophy in cardiomyocytes and is associated with left ventricular hypertrophy (LVH) in hypertensive patients. The objective of this study was to evaluate whether plasma CT-1 is associated with hypertrophic cardiomyopathy (HCM). The study was performed in 124 patients with HCM. All patients underwent a full clinical evaluation and an echocardiogram. Left ventricular hypertrophy was evaluated by the measurement of the maximal LV wall thickness and the Spirito's LVH score. Plasma CT-1 was measured by an enzyme-linked immunosorbent assay. Compared with controls, patients with HCM exhibited higher (P < 0.001) plasma CT-1 levels. Significant correlations were found between CT-1 and maximal LV wall thickness (r = 0.284, P = 0.001) and the Spirito's LVH score (r = 0.287, P = 0.006) in HCM patients. In addition, the levels of CT-1 were higher (P = 0.02) in patients with severe LVH (maximal LV wall thickness ≥30 mm) than in patients with mild or moderate LVH (maximal LV wall thickness <30 mm). These findings show that plasma CT-1 is associated with the severity of LVH in patients with HCM. Further studies are required to ascertain whether CT-1 is a diagnostic biomarker of this cardiomyopathy.European Heart Journal 11/2010; 32(2):177-83. · 10.48 Impact Factor -
Article: Novel human pathological mutations. Gene symbol: MYBPC3. Disease: cardiomyopathy, hypertrophic.
Human Genetics 04/2010; 127(4):483. · 5.07 Impact Factor -
Article: Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy.
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ABSTRACT: MyBPC3 mutations are amongst the most frequent causes of hypertrophic cardiomyopathy, however, its prevalence varies between populations. They have been associated with mild and late onset disease expression. Our objectives were to establish the prevalence of MyBPC3 mutations and determine their associated clinical characteristics in our patients. Screening by Single Strand Conformation Polymorphisms (SSCP) and sequencing of the fragments with abnormal motility of the MyBPC3 gene in 130 unrelated consecutive HCM index cases. Genotype-Phenotype correlation studies were done in positive families. 16 mutations were found in 20 index cases (15%): 5 novel [D75N, V471E, Q327fs, IVS6+5G>A (homozygous), and IVS11-9G>A] and 11 previously described [A216T, R495W, R502Q (2 families), E542Q (3 families), T957S, R1022P (2 families), E1179K, K504del, K600fs, P955fs and IVS29+5G>A]. Maximum wall thickness and age at time of diagnosis were similar to patients with MYH7 mutations [25(7) vs. 27(8), p = 0.16], [46(16) vs. 44(19), p = 0.9]. Mutations in MyBPC3 are present in 15% of our hypertrophic cardiomyopathy families. Severe hypertrophy and early expression are compatible with the presence of MyBPC3 mutations. The genetic diagnosis not only allows avoiding clinical follow up of non carriers but it opens new possibilities that includes: to take preventive clinical decisions in mutation carriers than have not developed the disease yet, the establishment of genotype-phenotype relationship, and to establish a genetic diagnosis routine in patients with familial HCM.BMC Medical Genetics 01/2010; 11:67. · 2.33 Impact Factor -
Article: A homozygous MYBPC3 gene mutation associated with a severe phenotype and a high risk of sudden death in a family with hypertrophic cardiomyopathy.
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ABSTRACT: Genetic studies can play a key role in the comprehensive evaluation of familiar hypertrophic cardiomyopathy and in the development of individualized medicine. Although only a few cases have been described, there exists a group of patients with complex genotypes that are associated with severe disease manifestations and a high risk of sudden death. We describe a family in which some members experienced the early development of systolic and diastolic dysfunction while others experienced sudden death at a young age. We identified a novel homozygous mutation (IVS6+5G>A) in the myosin-binding protein-C gene that explained the phenotype of affected individuals and that enabled us to estimate the risk in other family members and to offer genetic counseling.Revista Espa de Cardiologia 05/2009; 62(5):572-5. · 2.53 Impact Factor -
Article: Sudden death in a patient with lamin A/C gene mutation and near normal left ventricular systolic function.
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ABSTRACT: Mutations in the lamin A/C gene seem to be important aetiological factors in familial DCM. Heart disease caused by lamin A/C gene mutations is characterised by conduction system disorders with the need for permanent pacemaker implantations, atrial fibrillation, severe heart failure, and increased risk for sudden cardiac death. We described an asymptomatic 28-year-old man with a R190W lamin A/C gene mutation and mild left ventricular enlargement and near normal left ventricular ejection fraction who suffered from sudden cardiac death during sleeping. His electrocardiogram did not show conduction system disease and the most remarkable finding was a progressive decrease in voltage, which may be a marker of disease progression. The case study's mother had a similar phenotype to this and also had died suddenly. Sudden cardiac death in some lamin A/C gene mutations may occur even before the development of severe left ventricular dysfunction and implantable cardioverter-defibrillator should be early considered.International journal of cardiology 06/2008; 126(1):136-7. · 7.08 Impact Factor -
Article: Prevalence of fabry disease in a cohort of 508 unrelated patients with hypertrophic cardiomyopathy.
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ABSTRACT: We aimed to study the prevalence of Fabry disease (FD) in patients with hypertrophic cardiomyopathy (HCM). There are limited and controversial data about the prevalence of FD in patients with HCM. We screened the plasma alpha-galactosidase A activity from 508 unrelated patients with HCM (328 men, 180 women, ages 58 +/- 16 years). Patients with low activity (0% to 30% of the normal control in men, and 0% to 50% in women) underwent genetic study of the GLA gene. We found low plasma activity in 15 patients (3%). Three men had GLA mutations (0.9%): S238N (novel) in 2 and E358del (described) in 1. Two women had described mutations (1.1%): L89P and A143T. Three unrelated men had the D313Y variant previously associated with enzyme pseudo-deficiency. Two women had polymorphisms that did not segregate with the disease in their families. Five women (activity 39% to 47%) had no sequence variants. The familial studies allowed the diagnosis of 14 carriers: 6 women without Fabry manifestations, 3 women with cardiomyopathy, 2 men with renal and cardiac disease, 1 man with microhematuria, 1 woman with first-degree atrioventricular block, and a 32-year-old woman with only renal disease. By means of a screening based on genotyping of patients with low plasma enzymatic activity, the prevalence of FD in our population of HCM is 1% (0.9% in men and 1.1% in women). This diagnosis is relevant, because it allows the identification of disease carriers that might benefit from enzyme replacement therapy.Journal of the American College of Cardiology 01/2008; 50(25):2399-403. · 14.16 Impact Factor -
Article: Left ventricular asynchrony in patients with hypertrophic cardiomyopathy: its determinants and its relation to left ventricular function.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 12/2007; 20(11):1247-52. · 2.98 Impact Factor -
Article: Relation of left ventricular chamber stiffness at rest to exercise capacity in hypertrophic cardiomyopathy.
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ABSTRACT: The degree of exercise capacity is poorly predicted by conventional markers of disease severity in patients with hypertrophic cardiomyopathy (HC). The principal mechanism of exercise intolerance in patients with HC is the failure of stroke volume augmentation due to left ventricular (LV) diastolic dysfunction. The role of LV chamber stiffness, assessed noninvasively, as a determinant of exercise tolerance is unknown. Sixty-four patients with HC were studied with Doppler echocardiography, exercise testing, and gadolinium cardiac magnetic resonance. The LV chamber stiffness index was determined as the ratio of pulmonary capillary wedge pressure (derived from the E/Ea ratio) to LV end-diastolic volume (assessed by cardiac magnetic resonance). Maximal exercise tolerance was defined as achieved METs. There were inverse correlations between METs achieved and age (r = -0.38, p = 0.003), heart rate deficit (r = -0.39, p = 0.002), LV outflow tract gradient (r = -0.33, p = 0.009), the E/Ea ratio (r = -0.4, p = 0.001), mean LV wall thickness (r = -0.26, p = 0.04), and LV stiffness (r = -0.56, p <0.001) and a positive correlation between METs achieved and LV end-diastolic volume (r = 0.33, p = 0.01). On multivariate analysis, only LV chamber stiffness was associated with exercise capacity. A LV stiffness level of 0.18 mm Hg/ml had 100% sensitivity and 75% specificity (area under the curve 0.84) for predicting < or =7 METs achieved. In conclusion, LV diastolic dysfunction at rest, as manifested by increased LV chamber stiffness, is a major determinant of maximal exercise capacity in patients with HC.The American Journal of Cardiology 05/2007; 99(10):1454-7. · 3.37 Impact Factor -
Article: [Clinical significance of late gadolinium enhancement on cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy].
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ABSTRACT: In patients with hypertrophic cardiomyopathy, myocardial fibrosis can be detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. We investigated the relationships between the extent of LGE, left ventricular morphology and function, and clinical characteristics. Both cine and gadolinium-enhanced magnetic resonance imaging were performed in 104 patients with hypertrophic cardiomyopathy. Fifty patients (48%) showed LGE (range: 1-11 segments). The extent of LGE was positively correlated with maximum left ventricular wall thickness (r=0.53, P< .001), left ventricular mass (r=0.41, P< .001), and the number of hypokinetic segments (r=0.51, P< .001), and inversely correlated with ejection fraction (r=-0.32, P=.001), the magnitude of the subaortic gradient increase during exercise echocardiography (r=-0.26, P=.023), and age at diagnosis (r=-0.20, P=.04). Four of the five patients with an ischemic response on exercise echocardiography had > or =3 segments showing LGE (P=.003). Severe hypertrophy (i.e., > or =30 mm) and nonsustained ventricular tachycardia occurred more frequently as the number of LGE segments increased (P< .001 and P=.04, respectively). Extensive LGE reflects greater disease expression. It is associated with more severe myocardial damage (i.e., a lower ejection fraction and a larger number of hypokinetic segments) and with adverse clinical characteristics (e.g., young age at diagnosis, severe hypertrophy, nonsustained ventricular tachycardia, and an ischemic response on exercise), suggesting that it may be closely linked to prognosis.Revista Espa de Cardiologia 02/2007; 60(1):15-23. · 2.53 Impact Factor -
Article: [Beta-myosin heavy-chain gene mutations in patients with hypertrophic cardiomyopathy].
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ABSTRACT: To determine the frequency of mutations in the beta-myosin heavy-chain gene (MYH7) in a cohort of patients with hypertrophic cardiomyopathy (HCM) and their families, and to investigate correlations between genotype and phenotype. Single-strand conformation polymorphism analysis and sequencing of fragments with abnormal MYH7 gene mobility were carried out in 128 consecutive index patients with HCM. The phenotypes of patients with and without mutations were compared and the phenotypes of identified families were recorded. A total of 11 mutations were found in 13 families (10%); 7/11 had been previously described. The I736T mutation was found in three families and the A797T in two. One patient had two mutations (i.e., I736T and R787H). Mutations were more frequent in patients with a family history of sudden death (31%) and in those with severe hypertrophy (39% had a thickness > or = 30 mm). Mutations were found in 29 of 42 members of the 13 families, including six family members (20%) who were healthy carriers and aged < or = 36 years. Sudden death had occurred in eight members of four families: four in two families with the I736T mutation, one in a family with A797T, one in a family with R870H, and two in a family with A901P. MYH7 mutations were present in 10% of our families. Mutations were more frequent in patients with a family history of sudden death and in those with severe hypertrophy. Most mutations had been described previously. Some appeared in several families. For some mutations, the correlation between genotype and phenotype was stable, while for others, there were marked differences between the phenotypes of the index patients and their relatives, suggesting the presence of additional genetic factors that have yet to be identified.Revista Espa de Cardiologia 11/2006; 59(10):1008-18. · 2.53 Impact Factor -
Article: [The implantable cardioverter-defibrillator and hypertrophic cardiomyopathy. Experience at three centers].
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ABSTRACT: Although implantable cardioverter-defibrillators (ICDs) are recommended for high-risk patients with hypertrophic cardiomyopathy (HCM), there is no agreement on their general use. Moreover, little information is available on ICD use in this setting in Spain. Our aims were to describe the characteristics of HCM patients who received ICDs at three hospitals in Spain, and to study indications for device implantation and the results of follow-up in device users. We evaluated risk factors for sudden death in HCM patients with ICDs, including family history of sudden death, recurrent syncope, maximum wall thickness > or =30 mm, left ventricular outflow pressure gradient >30 mmHg, abnormal blood pressure response to exercise, and nonsustained ventricular tachycardia. During regular follow-up, appropriate and inappropriate administration of ICD therapy was recorded. Of 726 HCM patients, 45 (6.2%) had an ICD (mean age 43 [20] years). The proportion of patients with ICDs at the three centers studied was highly variable despite patients' clinical characteristics being similar. The indication for implantation was primary prevention in 27 patients and secondary prevention in 18. During follow-up (median 32 months), ICD therapy was administered appropriately in 10 (22.0%) patients (in nine, as secondary prevention and, in one, as primary prevention). The annual appropriate ICD therapy rate was 11.1% for secondary prevention and 1.6% for primary prevention. Two patients received an ICD to treat ventricular fibrillation and eight, to treat sustained ventricular tachycardia. The only significant predictor of appropriate ICD therapy was a history of sustained ventricular tachycardia or ventricular fibrillation (hazard ratio =13.3, P=.014). The percentage of HCM patients undergoing ICD implantation at Spanish hospitals was highly variable, possibly due to different selection criteria. When used as secondary prevention, ICD therapy was administered appropriately in a high proportion of cases (50% in 3 years).Revista Espa de Cardiologia 07/2006; 59(6):537-44. · 2.53 Impact Factor -
Article: Mutaciones en el gen de la cadena pesada de la betamiosina en pacientes con miocardiopatía hipertrófica
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ABSTRACT: Introducción y objetivos. Determinar la frecuencia de mutaciones en el gen de la cadena pesada de la beta-miosina (MYH7) en una cohorte de pacientes con miocar-diopatía hipertrófica (MCH) y en sus familiares, y analizar la correlación entre genotipo y fenotipo. Métodos. Detección de polimorfismo en la conforma-ción de hebras monocatenarias y secuenciación de frag-mentos con movilidad anormal del gen MYH7 en 128 ca-sos índice consecutivos con MCH. Comparación de fenotipo entre pacientes con y sin mutaciones y descrip-ción del fenotipo de las familias identificadas. Resultados. Identificamos 11 mutaciones en 13 fami-lias (10%), 7/11 previamente descritas. La mutación I736T se identificó en 3 familias y la A797T en 2. Un caso presentó 2 mutaciones (I736T y R787H). Las mutaciones fueron más frecuentes en pacientes con antecedentes fa-miliares de muerte súbita (31%) y con hipertrofia severa (39% con grosor ≥ 30 mm). Había mutación en 29 de 42 miembros de las 13 familias, incluidos 6 (20%) portadores sanos (edad ≤ 36 años). Había antecedentes de muerte súbita en 9 familiares de 4 familias (4 en 2 familias con I736T, uno con A797T, uno con R870H y 2 con A901P). Conclusiones. Las mutaciones en MYH7 aparecen en un 10% de nuestras familias y son más frecuentes cuando hay antecedentes familiares de muerte súbita o hipertrofia severa. La mayor parte había sido descrita previamente y algunas se repiten en varias familias. Ciertas mutaciones muestran una correlación genotipo-fenotipo estable, mien-tras que en otras, las marcadas diferencias entre casos índice y familiares hacen sospechar la presencia de facto-res genéticos adicionales que debemos identificar.Rev Esp Cardiol. 01/1008; 59. -
Article: Implantable Cardioverter Defibrillator and Hypertrophic Cardiomyopathy. Experience at Three Centers
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ABSTRACT: Introduction and objectivesAlthough implantable cardioverter-defibrillators (ICDs) are recommended for high-risk patients with hypertrophic cardiomyopathy (HCM), there is no agreement on their general use. Moreover, little information is available on ICD use in this setting in Spain. Our aims were to describe the characteristics of HCM patients who received ICDs at three hospitals in Spain, and to study indications for device implantation and the results of follow-up in device users.MethodsWe evaluated risk factors for sudden death in HCM patients with ICDs, including family history of sudden death, recurrent syncope, maximum wall thickness >30 mm, left ventricular outflow pressure gradient >30 mm Hg, abnormal blood pressure response to exercise, and nonsustained ventricular tachycardia. During regular follow-up, appropriate and inappropriate administration of ICD therapy was recorded.ResultsOf 726 HCM patients, 45 (6.2%) had an ICD (mean age 43 [20] years). The proportion of patients with ICDs at the three centers studied was highly variable despite patients' clinical characteristics being similar. The indication for implantation was primary prevention in 27 patients and secondary prevention in 18. During follow-up (median 32 months), ICD therapy was administered appropriately in 10 (22.0%) patients (in 9, as secondary prevention and, in 1, as primary prevention). The annual appropriate ICD therapy rate was 11.1% for secondary prevention and 1.6% for primary prevention. Two patients received an ICD to treat ventricular fibrillation and 8, to treat sustained ventricular tachycardia. The only significant predictor of appropriate ICD therapy was a history of sustained ventricular tachycardia or ventricular fibrillation (hazard ratio =13.3, P=.014).ConclusionsThe percentage of HCM patients undergoing ICD implantation at Spanish hospitals was highly variable, possibly due to different selection criteria. When used as secondary prevention, ICD therapy was administered appropriately in a high proportion of cases (50% in 3 years).Introducción y objetivosEl desfibrilador automático implantable (DAI) es el tratamiento recomendado en la miocardiopatía hipertrófica (MCH) de alto riesgo, aunque no hay acuerdo en sus indicaciones. Hay pocos datos so-bre su utilización en nuestro país. El objetivo es describir las características de los pacientes con MCH a los que se les implantó un DAI y analizar los resultados de esta tera-pia.MétodosSe analizaron los factores de riesgo de muerte súbita en los pacientes portadores de DAI de 3 centros con consultas dedicadas a la MCH (antecedentes personales y familiares de muerte súbita, síncope recu-rrente, grosor = 30 mm y gradiente subaórtico > 30 mmHg, respuesta anormal de la presión al esfuerzo y ta-quicardia ventricular no sostenida) y la indicación del im-plante. Se realizó un seguimiento periódico y se registra-ron las terapias adecuadas e inadecuadas.ResultadosDe 726 pacientes, 45 (6,2%) eran portadores de DAI (edad de 43 ± 20 años). La proporción de pacientes con DAI en los 3 centros fue muy variable, a pesar de que las características de los pacientes eran si-milares. La indicación fue prevención primaria en 27 pacientes y secundaria en 18. Con un seguimiento de 32 meses, 10 pacientes (22%) recibieron tratamiento ade-cuado (9 de prevención secundaria y uno de prevención primaria). La tasa anual de tratamientos adecuados fue del 11,1% en prevención secundaria y del 1,6% en prevención primaria. El único factor asociado con el trata-miento adecuado fue el antecedente de taquicardia ventricular sostenida o fibrilación ventricular (riesgo relativo [RR] = 13,3; p = 0,014).ConclusionesEn consultas dedicadas a la MCH, el porcentaje de pacientes portadores de DAI varía en fun-ción del grado de selección de la población de origen. La incidencia de terapias adecuadas es elevada en preven-ción secundaria (el 50% en 3 años).Revista Española de Cardiología (English Edition).
Top co-authors
Top Journals
Institutions
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2010
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Instituto de Investigación Biomédica de A Coruña
A Coruña, Galicia, Spain
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2009
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Complexo Hospitalario Universitario A Coruña
A Coruña, Galicia, Spain
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2006
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Hospital General Universitario de Alicante
Alicante, Valencia, Spain
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