Resumen Introducción y objetivos En España, el 0,3% de los pacientes hipertensos son refractarios al tratamiento convencional. Las complicaciones derivadas de un control deficiente se traducen en ...mala calidad de vida para el paciente y un coste importante para el sistema sanitario. Barostim es un dispositivo implantable que busca reducir la presión arterial de estos pacientes. El objetivo del presente estudio es analizar el coste-efectividad de Barostim comparado con terapia farmacológica en pacientes hipertensos refractarios al tratamiento convencional (al menos tres fármacos antihipertensivos, siendo uno de ellos un diurético). Métodos Modelo de Markov adaptado a la epidemiología de la población española que simula la historia natural de una cohorte de pacientes con hipertensión arterial refractaria a lo largo de su vida. Los datos sobre efectividad de los tratamientos se obtuvieron de la literatura y los de costes, de bases de datos administrativas hospitalarias y de fuentes oficiales. Se realizaron análisis de sensibilidad determinístico y probabilístico. Resultados Barostim redujo los eventos clínicos asociados a la hipertensión y aumentó en 0,78 el número de años de vida ajustados por calidad. El cociente de coste-efectividad incremental para una cohorte de varones alcanzó los 68.726 euros por año de vida ajustado por calidad. Uno de los principales elementos que encarece la tecnología es el coste del recambio de la batería. Los resultados fueron robustos. Conclusiones Barostim no es una estrategia coste-efectiva para el tratamiento de la hipertensión refractaria en España. Reducciones futuras en el precio de la batería mejorarían su cociente de coste-efectividad.
Background: Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the ...identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Methods and Findings: Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Conclusions: Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The clinical significance of a right bundle branch block (RBBB) in an asymptomatic adult without evidence of cardiovascular disease is controversial. To establish the relationship between the ...appearance of the RBBB and the increase of cardiovascular morbidity and mortality in healthy patients, we have carried out a literature review of documents available until September 2017 through a systematic search on the Pubmed database, Cochrane library and a manual search of the mentioned literature and related articles. From the 29 articles included in the study sample, eight showed mortality and 16 morbidity outcomes. An increase of risk of death is observed is eight articles and an increase of cardiovascular events is observed in 11 articles. The most recent publications suggest that the appearance of an RBBB in healthy individuals should not be underestimated, thus further studies are needed to analyse the type of follow-up that should be carried out in these patients.
La significación clínica que tiene un bloqueo de rama derecha (BRD) en los pacientes asintomáticos sin evidencia de patología cardiovascular conocida es fuente de controversia. Para establecer la relación entre la aparición del BRD y el aumento de morbimortalidad cardiovascular en pacientes sanos se realizó una revisión bibliográfica de los artículos existentes hasta septiembre de 2017, a través de la búsqueda sistemática en PubMed, Cochrane y búsqueda manual de la bibliografía citada y artículos relacionados. De las 29 publicaciones que cumplían los criterios de inclusión, 8 mostraron resultados de mortalidad y 16 de morbilidad. En 8 artículos se observó un aumento de riesgo de muerte y en 11 de eventos cardiovasculares. Las publicaciones revisadas sugieren que la presencia de BRD en pacientes sanos no es irrelevante. Se necesitan más estudios que analicen qué tipo de seguimiento se debería realizar en estos pacientes.
Highlights • Catecholaminergic polymorphic ventricular tachycardia is a cause of sudden death. • Molecular autopsy should be performed in sudden death cases showing normal autopsy. • Next Generation ...Sequencing technology allows a comprehensive genetic analysis. • Familial assessment is crucial to identify relatives at risk of sudden death
Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid ...(FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.
RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).
Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.
DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Resumen Introducción y objetivos La taquicardia ventricular polimórfica catecolaminérgica (TVPC) es una enfermedad hereditaria caracterizada por arritmias ventriculares (AV) polimórficas o ...bidireccionales desencadenadas por estrés físico o emocional en jóvenes con corazón estructuralmente normal. El pilar del tratamiento son los bloqueadores beta y recientemente se ha incorporado la flecainida al arsenal terapéutico. El objetivo de este trabajo es exponer nuestra experiencia con su uso. Métodos De un total de 174 pacientes pertenecientes a 7 familias afectadas de TVPC con genotipo positivo, se analizó a los que tomaron flecainida. Se valoraron la indicación, los efectos secundarios, la dosificación, los eventos clínicos, las AV y la ventana arrítmica en las pruebas de esfuerzo y las descargas del desfibrilador automático (DAI). Resultados Recibieron flecainida 18 pacientes (10,4%); 17 en combinación con bloqueadores beta y 1 como tratamiento único por intolerancia al bloqueador beta. Ningún paciente sufrió efectos secundarios. La indicación fue la persistencia de AV complejas en la prueba de esfuerzo en 13 pacientes (72,2%) y descargas frecuentes del DAI en los otros 5 (27,8%). En el 66,7% de la familia 1, la puntuación cuantitativa de AV en la prueba de esfuerzo se redujo más de un 50% (32,76 ± 84,06 frente a 74,38 ± 153,86 lpm; p = 0,018). La ventana arrítmica fue menor (5,8 ± 11,9 frente a 19,69 ± 21,27 lpm; p = 0,007) y 4 de los 5 pacientes con descargas apropiadas del DAI no sufrieron más descargas. Conclusiones En pacientes con TVPC, la flecainida reduce los eventos clínicos, las AV, la ventana arrítmica y las descargas del DAI y los pacientes la toleran bien.
PURPOSE: Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs ...and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. METHODS: 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). RESULTS: The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. CONCLUSION: CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since the introduction of molecular biology techniques hereditary diseases can be studied. These techniques allow us to locate the gene that causes a disease in a family. The identification of this ...gene not only permits to diagnose and potentially treat those affected by the abnormal gene, but also helps in a better understanding of the pathophysiology and molecular basis of non-familial forms of the disease. Although these techniques have been incorporated slowly in the field of cardiology, now the speciality is completely submerged in molecular biology. The first gene that was found was that of hypertrophic cardiomyopathy, in 1989. Since then, we have advanced in all heart family illnesses. Hypertension, arteriosclerosis, congenital diseases and arrhythmias have benefited from these techniques. The understanding of arrhythmias that cause familial sudden death due to long QT syndrome or Brugada syndrome has progressed a lot. The first genetically guided therapy studies have shown that in the near future patients will receive a therapy according to their genetical default. Looking how fast these techniques are evolving, and the impressive advances of the Human Genome Project, probably the remaining genes causing familial diseases will be described in the coming years. These results are very encouraging and indicate a clear need to make a genetic diagnosis in all patients with these diseases. The diagnostic and therapeutic implications of these findings can be of enormous importance for our patients.
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