Correlación genotipo-fenotipo en miocardiopatía hipertrófica: un estudio multicéntrico en Portugal y España sobre la variante p. Arg21Leu de TPM1 / Genotype-phenotype correlations in hypertrophic cardiomyopathy: a multicenter study in Portugal and Spain of the TPM1 p. Arg21Leu variant

Introducción y objetivos: TPM1 es uno de los principales genes en la miocardiopatía hipertrófica (MCH). La información clínica sobre portadores es relativamente escasa, lo cual limita la interpretación de los estudios genéticos. Nuestro objetivo es establecer la correlación genotipo-fenotipo de la variante p.Arg21Leu de TPM1 en una serie de familias. Métodos: Se evaluó el TPM1 mediante secuenciación de nueva generación en 10.561 probandos con cardiopatías hereditarias. Se genotipificó a los familiares mediante Sanger. Se analizaron la cosegregación, las características clínicas y los eventos cardiovasculares. Se estimó la distribuición geográfica de las familias en Portugal y España. Resultados: Se identificó la variente p.Arg21Leu de TPM1 en 25/4.099 (0,61%) casos con MCH y estaba ausente en 6.462 controles con otras cardiopatías familiares (p<0,0001). Se identificó a 83 portadores (31 probandos). La LOD score combinada para cosegregación fue 3,95. La probabilidad acumulada de diagnóstico en portadores a los 50 años fue del 50% para los varones y el 25% para las mujeres. El 17 de los varones y el 46% de las mujeres no estaban afectadas a los 70 años. El grosor medio del ventrículo izquierdo fue 21,4 ±7,65mm. El riesgo de muerte súbita-MCH fue bajo en 34 (77,5%), intermedio en 8 (18%) y alto en 2 (4,5%) de los portadores. La supervivencia libre de eventos cardiovasculares fue del 87,5% a los 50 años. El 6% de los portadores eran homocigotos y el 18% tenían una variante adicional. El origen de las familias se concentró en Galicia, Extremadura y norte de Portugal, lo que indica un efecto fundador. Conclusiones: P.Arg21Leu es una variante patogénica de TPM1 asociada con MCH de penetrancia tardía/incompleta y pronóstico generalmente favorable (AU)

Introduction and objectives: TPM1 is one of the main hypertrophic cardiomyopathy (HCM) genes. Clinical information on carriers is relatively scarce, limiting the interpretation of genetic findings in individual patients. Our aim was to establish genotype-phenotype correlations of the TPM1 p.Arg21Leu variant in a serie of pedigrees. Methods: TPM1 was evaluated by next-generation sequencing in 10 561 unrelated probands with inherited heart diseases. Familial genetic screening was performed by the Sanger method. We analyzed TPM1 p.Arg21Leu pedigrees for cosegregation, clinical characteristics, and outcomes. We also estimated the geographical distribution of the carrier families in Portugal and Spain. Results: The TPM1 p.Arg21Leu variant was identified in 25/4099 (0.61%) HCM-cases, and was absent in 6462 control individuals with other inherited cardiac phenotypes (P<.0001). In total, 83 carriers (31 probands) were identified. The combined LOD score for familial cosegregation was 3.95. The cumulative probability of diagnosis in carriers was 50% at the age of 50 years for males, and was 25% in female carriers. At the age of 70 years, 17% of males and 46% of female carriers were unaffected. Mean maximal left ventricular wall thickness was 21.4 ±7.65mm. Calculated HCM sudden death risk was low in 34 carriers (77.5%), intermediated in 8 (18%), and high in only 2 (4.5%). Survival free of cardiovascular death or heart transplant was 87.5% at 50 years. Six percent of carriers were homozygous and 18% had an additional variant. Family origin was concentrated in Galicia, Extremadura, and northern Portugal, suggesting a founder effect. Conclusions: TPM1 p.Arg21Leu is a pathogenic HCM variant associated with late-onset/incomplete penetrance and a generally favorable prognosis (AU)

[Actuarial follow-up after percutaneous mitral valvulotomy. Incidence and event-predicting factors]. / Seguimiento actuarial tras valvulotomía mitral percutánea. Incidencia y factores predictores de eventos.

INTRODUCTION: The goal of this study is to analyse the follow-up of patients who underwent percutaneous mitral valvuloplasty and the predicting factors of event-free survival. METHODS: We analysed 220 consecutive valvuloplasty performed between 1988 and 1996 in order to establish the incidence of events (death, restenosis, mitral valve surgery, New York Heart Association class IV, new valvuloplasty or systemic embolia) and the baseline and postprocedural characteristics predicting events, during a mean follow-up of 42 months (range 1-96 months). RESULTS: Overall survival was 94.7%, and event-free survival was 59.2% at 96 months. We analyzed the baseline characteristics in order to predict the mid-term outcome (actuarial survival Kaplan-Meier method) that atrial fibrillation (p < 0.01), age > or = 56 years (p < 0.005), and echocardiographic score > or = 9 (p < 0.005) were baseline characteristics related to adverse events in follow up. An index based on the number of adverse factors in the baseline characteristics provided a significant difference in concerning the number of follow up to even-free between the group without baseline adverse characteristics and the group with two (p = 0.008, OR = 4.5), or three adverse characteristics (p = 0.005, OR 6.4). Among the postprocedural characteristics, while patients with mitral valve area after valvuloplasty > or = 1.5 cm2 had an event-free survival of 72.9% at 96 months, those with postprocedural mitral valve area < 1.5 cm2 had an event-free survival of 10.5% (log-rank test p < 0.0001). CONCLUSIONS: Mid-term event-free survival after percutaneous mitral balloon valvuloplasty can be predicted by baseline and postprocedural characteristics. Age > or = 56, echocardiographic score > or = 9 and atrial fibrillation are baseline factors related with adverse events. Patients with 0 or 1 baseline adverse factors do not have significant differences concerning mid-term outcome while, those with 2, and above all, 3 adverse baseline characteristics have a poorer event-free survival. Mitral valve area > or = 1.5 cm2 is the only postprocedural independent predictor of event-free survival.

[The imaging diagnosis of pericardial agenesis]. / Diagnóstico de imagen de la agenesia de pericardio.

Pericardial agenesis is a rare anomaly, difficult to diagnose. Its evolution is usually benign. However, on rare occasions, partial defects have been the cause of sudden death. Therefore, surgical treatment has sometimes been indicated, even though in the cases were asymptomatic. We report the case of a 50 year-old woman with partial pericardial agenesis and herniation of left atrial appendage trough. The defect was discovered by a routine chest x-ray and treated in a conservative way. Current diagnostic and therapeutic techniques are reviewed.

[Diagnostic criteria of infective endocarditis: from Von Reyn to Duke. Transthoracic and transesophageal echocardiography]. / Criterios diagnósticos de endocarditis infecciosa de Von Reyn a Duke. Ecocardiografía transtorácica y transesofágica.

The Von Reyn criteria determine only a small number of definitive diagnoses of infectious endocarditis, while it is mainly diagnosed by histopathological confirmation in surgery or autopsy. This necessitates carrying out a new diagnostic scheme with accurate sensitivity and specificity based on rigorous clinical support. This scheme is provided by the Duke University criteria, which enhance the role of conventional and transesophageal echocardiography, in the diagnosis of infectious endocarditis. Echocardiography is the only accurate procedure for a non invasive diagnosis of vegetation, the main lesion in this pathology. Often, tissue destruction causes regurgitation, which is responsible for hemodynamic impairment or allows the spread of the infectious process to perivalvular tissue and can form an abscess. These complications and many others, which are difficult to treat, require an early diagnosis of this disease. Sensitivity of transesophageal technique to detect vegetations and complications is higher than that observed in conventional echocardiography, above all in patients with prosthetic valves. If the transesophageal study is negative, the existence of an infectious endocarditis is quite unlikely. Nevertheless, we need to consider clinical features, as the specificity of this technique is moderate.

[Diastolic dysfunction, left ventricular hypertrophy, and microalbuminuria in mild to moderate essential arterial hypertension]. / Disfunción diastólica, hipertrofia ventricular izquierda y microalbuminuria en la hipertensión arterial esencial ligera-moderada.

INTRODUCTION: It is known, that there is a high prevalence of left ventricular diastolic disfunction, which precedes left ventricular hypertrophy in hypertensive people, but there is little published in literature about the relationship between these findings and the presence of microalbuminuria. OBJECTIVE: In our study, we pretend to evaluate prevalence and eventual relation among microalbuminuria, diastolic disfunction and left ventricular hypertrophy, in young mild to moderate hypertensive patients, non diabetic and without previous treatment. MATERIAL AND METHODS: We studied prospectively 80 untreated hypertensive patients, with normal serum creatinine, and non diabetic (52.5% women and 47.5% men, mean age 41.4 +/- 9.6 years). We evaluated filling indexes by Doppler Echocardiography: Ratio of early to late diastolic peak filling velocity and early filling deceleration time. Left ventricular hypertrophy was defined by Devereux's criteria. Microalbuminuria in twenty four hours was measured by radioimmunoassay in hypertensive patients (microalbuminuria: 30-300 mg/24 hours). RESULTS: Microalbuminuria occurred in 23.7%, left ventricular hypertrophy 40%, and diastolic disfunction 48.8%, no significant correlation existed between the same. Only 29.5% had no cardiac or renal disease. Statistically significant differences were found in ratio of early to late diastolic peak filling velocity and microalbuminuria, between the two study populations, but multiple regression analysis didn't prove such correlation. Ratio of early to late diastolic peak filling velocity was independently related to age and diastolic blood pressure. CONCLUSIONS: There is a high prevalence of cardiac and/or renal disease in mild hypertensive patients, only 29.5% of these patients are free of disease. We don't find relation between lesions in these organs.