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Background Over 70 genes that encode different cell components have been involved in the aetiology of dilated cardiomyopathy. Genotype-phenotype interactions are an unsolved problem, and to a large extent the effects of mutations in the expression mechanisms involved in the disease remain unknown, although associations are increasingly being established which have clinical and prognostic implications. Methods and results The objective of our work was to describe our population that has cardiomyopathy associated with mutations in the gene RBM20, and study the genotype-phenotype relationship. We studied 8 cases undergoing follow-up at our Unit, and collected data for demographic, clinical and diagnostic testing variables. The mean age on diagnosis was 55 years [52–59], with a median follow-up of 31.5 months [26.0–67.3]. It is worth noting that 62.5% of the patients in our group had a history of cardiomyopathy in first degree relatives, and 37.5% of them had a family history of sudden death. One of the genetic variations of the sample was shared by three subjects who had no apparent family relationship with each other, and this variation had not been described in controls. It is also interesting that arrhythmic events were found in 37.5% of the sample, and 50% of patients had an indication for implantable cardiac defibrillator. Conclusion This is the first analysis of patients with RBM20 mutations conducted in our country, and it indicates a profile with prominent arrhythmogenesis, a high penetrance of familial cardiomyopathy, and sudden death.

Introduction and objectives Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty replacement of predominantly right ventricular myocardium . This cardiomyopathy is a frequent cause of sudden cardiac death in young people and athletes. The aim of our study was to determine the incidence of pathological or likely pathological desmosomal mutations in patients with high-risk definite ARVC. Methods This was an observational, retrospective cohort study , which included 36 patients diagnosed with high-risk ARVC in our hospital between January 1998 and January 2015. Genetic analysis was performed using next-generation sequencing . Results Most patients were male (28 patients, 78%) with a mean age at diagnosis of 45 ± 18 years. A pathogenic or probably pathogenic desmosomal mutation was detected in 26 of the 35 index cases (74%): 5 nonsense, 14 frameshift, 1 splice, and 6 missense. Novel mutations were found in 15 patients (71%). The presence or absence of desmosomal mutations causing the disease and the type of mutation were not associated with specific electrocardiographic, clinical, arrhythmic, anatomic, or prognostic characteristics. Conclusions The incidence of pathological or likely pathological desmosomal mutations in ARVC is very high, with most mutations causing truncation. The presence of desmosomal mutations was not associated with prognosis.

Resumen Introduccion y objetivos La miocardiopatia arritmogenica del ventriculo derecho (MCAVD) es una cardiopatia hereditaria definida por la sustitucion progresiva de miocardio ventricular derecho por tejido fibroadiposo. Es causa frecuente de la muerte subita de jovenes atletas. El objetivo del presente estudio es conocer la incidencia de variantes desmosomicas patogenicas o probablemente patogenicas en pacientes con MCAVD definitiva de alto riesgo. Metodos El estudio de cohortes retrospectivo observacional incluyo a 36 pacientes diagnosticados de MCAVD definitiva de alto riesgo en nuestro hospital entre enero de 1998 y enero de 2015. El analisis genetico se realizo con next-generation sequencing. Resultados La mayoria eran varones (28 pacientes, 78%) con una media de edad al diagnostico de 45 ± 18 anos. Se detecto al menos 1 variante desmosomica patogenica o probablemente patogenica en 26 de los 35 casos indice (74%): 5 nonsense, 14 frameshift, 1 splice y 6 missense. En 15 pacientes (71%) se encontraron mutaciones nuevas. La presencia o la ausencia de mutaciones desmosomicas o la naturaleza de estas no se asociaron con caracteristicas electrocardiograficas, clinicas, arritmicas, anatomicas o pronosticas especificas. Conclusiones La incidencia de variantes desmosomicas patogenicas o probablemente patogenicas en MCAVD definitiva de alto riesgo fue muy alta, con mayoria de mutaciones que causan truncamiento. La presencia de mutaciones desmosomicas no se asocio con el pronostico.

INTRODUCTION Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The variable phenotype suggesting that determined environmental factors may have an influence. The aim of our study was to discover the impact of the dynamic physical activity on patients with high-risk definite ARVC/D. METHODS AND RESULTS Collection of data on physical activity at the time of diagnosis was conducted at an in-person clinical interview. The intensity of the activity was classified in accordance with the mean frequency of weekly physical exercise sessions in the 10 years before diagnosis and into the following three groups of dynamic activity: high/competitive (>3 h/wk), moderate (1 to 3 h) and minimal/inactive (

Resumen Las nuevas tecnicas desarrolladas para el analisis genetico nos aportan informacion sobre las bases geneticas de las distintas miocardiopatias, entre ellas, de la miocardiopatia dilatada familiar. Realizamos esta revision con el fin de aportar informacion sobre la utilidad clinica del estudio genetico en el manejo de estos pacientes.

Resumen Introduccion El objetivo del estudio fue conocer la prevalencia de pluripatologia y la utilidad del indice PROFUND para la estratificacion pronostica de los pacientes pluripatologicos en una unidad de hospitalizacion de Cardiologia. Pacientes y metodos Se analizaron de forma consecutiva todos los pacientes ingresados en 2012 en el servicio de Cardiologia. Se registraron las comorbilidades, estancia y mortalidad intrahospitalarias, y los indices de Charlson y PROFUND. En los pacientes pluripatologicos, se registraron ademas los reingresos y la mortalidad durante un ano de seguimiento. Resultados Se incluyeron 1.033 pacientes (67 ± 13,1 anos, 35% mujeres); 381 (36,9%) fueron pluripatologicos, con un indice de Charlson de 6,4 ± 1,7 y PROFUND de 2,5 ± 2,5. Comparados con el resto, los pluripatologicos fueron mayores (72 vs. 64 anos, p Conclusiones Un alto porcentaje de los pacientes ingresados en Cardiologia fueron pluripatologicos. Estos presentaron mayor prevalencia de factores de riesgo cardiovascular, mayor estancia y mortalidad intrahospitalarias. El indice PROFUND predijo de forma independiente la mortalidad y los acontecimientos adversos durante el seguimiento.

Introduction The aim of this study was to understand the prevalence of comorbidities and the usefulness of the PROFUND index for the prognostic stratification of patients with comorbidities in a hospital cardiology unit. Patients and methods We consecutively analysed all patients hospitalized in 2012 in the department of cardiology. We recorded the comorbidities, length of stay, hospital mortality, Charlson indices and PROFUND indices. In the patients with comorbidities, we also recorded the readmissions and mortality during a 1-year follow-up. Results The study included 1033 patients (mean age, 67 ± 13.1 years; 35% women), 381 (36.9%) of whom had comorbidities, with a mean Charlson index of 6.4 ± 1.7 and a mean PROFUND index of 2.5 ± 2.5. Compared with the other patients, the patients with comorbidities were older (72 vs. 64 years, p Conclusions A high percentage of patients hospitalized in the department of cardiology had comorbidities. These patients had a higher prevalence of cardiovascular risk factors, longer stays and greater hospital mortality. The PROFUND index independently predicted mortality and adverse events during the follow-up.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC/D) is an inherited cardiomyopathy characterized by ventricular arrhythmias and heart failure. The aim of our study was to analyze the impact of the ICD indication in the prognosis of patients with high-risk ARVC/D according to the consensus document. Methods The high-risk category includes patients who experienced cardiac arrest due to sustained ventricular tachycardia or ventricular fibrillation and patients with severe right or left ventricular dysfunction. We included 41 patients with high-risk ARVC/D: 33 in secondary prevention and 8 in primary prevention. Results We followed 41 patients during 6.37 ± 4.88 years. Twenty-six patients (63.4%) had at least one appropriate arrhythmic event: 24 p (72.7%) in secondary prevention and 2 p (25%) in primary prevention; p=0.02. Twenty-four patients (72.7%) in secondary prevention and five (62.5%) in primary prevention had a cardiovascular event such as arrhythmias, admission due to heart failure, heart transplantation or cardiovascular death. Conclusions High-risk ARVC/D patients had a high number of cardiovascular events, but their nature and treatment were different. Arrhythmic prognosis was worse in secondary prevention and most of the events found in primary prevention were related to heart failure and, therefore, without benefit of the ICD.

Background Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables. Methods We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM. Results LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6–6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98–4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors. Conclusions SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

[Abstract] Epicardial adipose tissue has been proposed to participate in the pathogenesis of heart failure. The aim of our study was to assess the expression of thermogenic genes (Uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and PR-domain-missing 16 (PRDM16) in epicardial adipose tissue in patients with heart failure, stablishing the difference according to left ventricular ejection fraction (reduced or preserved). Among the 75 patients in our study, 42.7% (n=32) had reduced left ventricular ejection fraction. UCP1, PGC1α and PRDM16 mRNA in EAT were significantly lower in patients with reduced left ventricular ejection fraction. Multiple regression analysis showed that age, male gender, body max index, presence of obesity, type-2-diabetes mellitus, hypertension and coronary artery disease and left ventricular ejection fraction were associated with the expression levels of UCP1, PGC1α and PRDM16 mRNA. Thermogenic genes expressions in epicardial adipose tissue (UCP1: OR 0.617, 95%CI 0.103-0.989, p=0.042; PGC1α: OR 0.416, 95%CI 0.171-0.912, p=0.031; PRDM16: OR 0.643, 95%CI 0.116-0.997, p=0.044) were showed as protective factors against the presence of heart failure with reduced left ventricular ejection fraction, and age (OR 1.643, 95%CI 1.001-3.143, p=0.026), presence of coronary artery disease (OR 6.743, 95%CI 1.932-15.301, p

Thepresenceoflategadoliniumenhancement(LGE)incardiacmag-netic resonance (CMR), that enables quantification of myocardialfibro-sis[1],iscommoninpatientswithnonischemicdilatedcardiomyopathy(NIDC). LGE has been related to adverse clinical outcomes in patientswith NIDC, mainly in those with idiopathic dilated cardiomyopathy[1,2]. This study pretends to assess the long-term prognostic signifi-cance of LGE in an unselected population of patients with NIDC. Everyunderlying possible cause was included.Weperformed aretrospective cohortstudyinwhich64consecutiveoutpatients with heart failure secondary to NIDC were included. Allunderwent a CMR between August 2005 and November 2011. Thepresence and location of LGE were evaluated.Diagnosis was established according to the World HealthOrganization/International Society and Federation of Cardiology'sdefinition [3]. None of the patients presented previous history ofsignificant valvular disease, hypertrophic cardiomyopathy, restrictivecardiomyopathy, congenital heart disease, or coronary artery disease.PatientsunderwentCMRjustafterthediagnosisofNIDCtocompletethe diagnostic evaluation. Exclusion criteria were: cardiac pacemaker/implantable cardioverter defibrillator (ICD)/cardiac resynchronizationtherapy, renal insufficiency and severe obesity or claustrophobia.Patientswerefollowedviaclinicalvisits.Theprimaryoutcomewasacomposite endpoint of three events: cardiac death, hospitalization forheart failure and appropriate ICD firing. ICD devices were implanted insome patients after they underwent CMR.CMRimagingwasperformedona1.5Teslascanner(PhilipsMRSys-tem Achieva Release 2.6.3.7). Delayed contrast-enhanced images wereacquired 10 min after intravenous administration of 0.2 mmol/kg ofgadolinium-diethylenetriaminepentaacetate, using inversion-recoveryfast gradient-echo pulse sequences in sequential short- and long-axisslices of the left ventricle.Allstudies were analyzedby aradiologistand acardiologist usinga workstation (Extended MR Work Space 2.6.2.4.). The presence andlocation of LGE were visually assessed.Qualitativevariableswereexpressedaspercentagesandquantitativeasmean±SD.Qualitativevariableswerecomparedwiththeχ

Left ventricular reverse remodeling (LVRR) in dilated cardiomyopathy is poorly known within the context of current therapeutic approach. Our goal is to describe the present incidence of LVRR, the factors able to predict it and the long term prognosis of these patients.We performed a retrospective analysis of a cohort or 387 consecutive outpatients. Mean follow-up was 50.4 ± 28.4 months. Sustained LVRR occurred in 57.6% of patients. The number of coronary arteries with severe stenosis (HR 0.69, 95% CI 0.55-0.86; p=0.001), New York Heart Association Functional Class (NYHA FC) (HR 0.39, 95% CI 0.27-0.54; p0.001) as well as the severity of mitral regurgitation (MR) at the end of follow-up (HR 0.42, 95% CI 0.30-0.58; p0.001) and the time until first event (HR 1.02, 95% CI 1.01-1.03; p0.001) were independent predictors of left ventricular ejection fraction improvement. LVRR was tightly related to prognosis due to the fact that both improvement in cardiac function achieving normal or slightly impaired LVEF (HR 0.31, 95% CI 0.17-0.56; p0.001) and shorter time to achieve LVRR (HR 0.99, 95% CI 0.98-0.99; p=0.017) formed part of the best model for predicting events in DCM.More than half of the patients showed sustained LVRR associated with a significantly better prognosis. Fewer numbers of coronary arteries with severe stenosis, milder NYHA FC and the absence of significant MR at the end of follow-up as well as longer event free period formed a simple model to prognosticate LVRR. LVRR and the time to achieve it were strongly related to long term prognosis in patients with DCM.

La determinacion de factores clinicos predictivos de la presencia de enfermedad coronaria podria obviar la necesidad de realizar una coronariografia en pacientes seleccionados con estenosis aortica severa. Se estudio a 315 pacientes (68 ± 8 anos) sin infarto previo con estenosis aortica severa a los que se realizo coronariografia. En el analisis univariable, resultaron significativas la edad (p = 0,001), la dislipemia (p = 0,003), la angina (p = 0,018), el gradiente aortico (p = 0,001) y la fraccion de eyeccion (FE) reducida (p = 0,006). En el analisis multivariable las variables asociadas de forma independiente a la lesion coronaria fueron la edad (odds ratio [OR] = 1,079, p = 0,01), la FE < 40% (OR = 2,685, p = 0,02), la angina (OR = 2,518, p = 0,04) y la dislipemia (OR = 2,34, p = 0,008). La disfuncion ventricular se correlaciona de forma independiente con la presencia de lesiones coronarias

Identification of clinical factors associated with coronary artery disease could obviate the need for coronary angiography in selected patients with severe aortic stenosis. We studied 315 patients (68 [8] years) with severe aortic stenosis without previous infarction who underwent coronary angiography. In the univariate analysis, age (P = .001), dyslipidemia (P = .003), angina (P = .018), aortic gradient (P = .001) and reduced ejection fraction (P = .006) were predictors of coronary artery disease. After multivariate analysis, age (OR = 1.079, P = .01), ejection fraction < 40% (OR = 2.685, P = .02), angina (OR = 2.518, P = .04) and dyslipidemia (OR = 2.34, P = .008) were the factors independently associated with coronary artery disease. Left ventricular dysfunction correlated independently with the presence of coronary artery disease.

Introduccion y objetivos La obstruccion dinamica intraventricular izquierda puede aparecer ocasionalmente en pacientes sin miocardiopatia hipertrofica. Planteamos si podria aparecer inducida por esfuerzo en pacientes con angina o disnea de esfuerzo sin causa aparente. El objetivo de este estudio prospectivo es conocer: a) si aparece con esfuerzo; b) su incidencia, magnitud y factores determinantes, y c) evolucion de los pacientes que la presentan. Pacientes y metodo Realizamos ecocardiograma- Doppler basal y postesfuerzo en 211 pacientes con angina o disnea de esfuerzo. Excluimos a los que tenian infarto previo, valvulopatia, disfuncion ventricular o hipertrofia ventricular sin hipertension. Definimos obstruccion dinamica intraventricular como flujo intraventricular con velocidad . 2,5 m/s. Resultados Se incluyo a 134 pacientes (59 mujeres), con una edad de 58 ± 9 anos; el 69,7% tenia antecedentes de hipertension, el 35%, dislipemia y el 24,6%, diabetes. Aparecio obstruccion intraventricular en 18 (13,4%) pacientes, con un gradiente entre 25 y 53 mmHg (media, 32,19 ± 6,6). Las variables demograficas, los factores de riesgo y el ejercicio realizado fueron similares en el grupo A (con obstruccion) y B (sin obstruccion). En el grupo A, ningun paciente tuvo evidencia de isquemia y los 5 que presentaron sintomas durante el esfuerzo tuvieron mayores gradientes (42,65 ± 10,5 frente a 28,15 ± 2,37 mmHg; p Conclusiones Nuestros datos sugieren que algunos pacientes con angina o disnea de esfuerzo sin evidencia de isquemia pueden tener obstruccion dinamica ventricular izquierda inducida por esfuerzo.

a Seccion de Cardiologia, Unidad de Medicina Interna, Hospital de Poniente, Carretera de Almerimar s/n, 04700 El Ejido, Almeria, Spain b Area del Corazon, Hospital Universitario Virgen de la Victoria, Campus Teatinos s/n, 29010 Malaga, Spain c Seccion de Cardiologia, Unidad de Medicina Interna, Fundacion Hospital Calahorra, Carretera de Logrono s/n, 26500 Calahorra, La Rioja, Spain d Unidad de Cardiologia, Hospital Parque San Antonio, Avenida Pintor Joaquin Sorolla n°2, 29016, Malaga, Spain

71 Rev Esp Cardiol 2004;57(12):1179-87 1179 Introduction and objectives. Dynamic left intraventri- cular outflow tract obstruction occurs occasionally in pa- tients without hypertrophic cardiomyopathy. We hypothe- sized that dynamic intraventricular obstruction might occur during effort in patients with angina or dyspnea wit- hout evident disease. The objective of this prospective study was to investigate: a) whether it appears with effort; b) its incidence, magnitude and determining factors; and c) its clinical course. Patients and method. We performed baseline and stress Doppler echocardiography in 211 patients with an- gina, dyspnea, or both with exercise. Patients with pre- vious myocardial infarction, valvular heart disease, ventri- cular dysfunction or ventricular hypertrophy without hypertension were excluded. Dynamic intraventricular obs- truction was defined as intracavitary flow velocity ≥2.5 m/s. Results. 134 patients (59 women) were included: mean age was 58 (9) years; history of hypertension was present in 69.7%, dyslipidemia in 35.8%, and diabetes in 24.6%. Dynamic intraventricular obstruction appeared in 18 pa- tients (13.4%), with gradients ranging between 25 and 53 mm Hg (mean, 32.19 (6.6)). Demographic variables, car- diovascular risk factors, and exercise performed were si- milar in group A (with obstruction) and group B (without obstruction). No patient in group A had evidence of ische- mia. Five patients in this group had symptoms during exercise; the gradients were greater in these patients (42.65 (10.5) vs 28.15 (2.37) mm Hg; P