RESUMEN
The aim of this study was to characterize the mutational spectrum of pulmonary hypertension (PH) patients through a next generation sequencing platform. In a total of 22 patients, the BMPR2, SMAD9, CAV1, KCNK3, and EIF2AK4 genes were sequenced with semiconductor chips and the ion torrent personal genome machine. We found six putative mutations in SMAD (p.R263Q), BMPR2 (p.S301P, p.T493I), CAV1 (p.V155I), and EIF2AK4 (p.L489P, p.P1115L) in five patients. One patient was compound heterozygous for BMPR2 + SMAD mutations, and one patient was homozygous for EIF2AK4 p.P1115L. The reported procedure would facilitate the rapid mutational screening of large cohorts of PH patients.
Asunto(s)
Hipertensión Pulmonar/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Adulto , Anciano , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/genética , Caveolina 1/genética , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas/métodos , Genómica , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Mutación , Proteínas del Tejido Nervioso/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/instrumentación , Canales de Potasio de Dominio Poro en Tándem/genética , Proteínas Serina-Treonina Quinasas/genética , Semiconductores , Proteína Smad8/genética , EspañaRESUMEN
BACKGROUND: In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. METHODS: The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and 'complicated course', which consisted of death from any cause, haemodynamic collapse or recurrent PE. RESULTS: MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). CONCLUSIONS: The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT-RVD and prognosis.
Asunto(s)
Tomografía Computarizada Multidetector/métodos , Embolia Pulmonar/diagnóstico por imagen , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Embolia Pulmonar/complicaciones , Embolia Pulmonar/mortalidad , Embolia Pulmonar/fisiopatología , Medición de Riesgo/métodos , España/epidemiología , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/mortalidadRESUMEN
Pulmonary arterial hypertension and secondary pleural effusion have been reported in association with long-term therapy with the multi-tyrosine kinase inhibitor dasatinib, approved for the treatment of chronic myeloid leukemia. Here, we present the case of a 50-year-old man, diagnosed with chronic myeloid leukemia in August 2003, who developed pulmonary arterial hypertension after > 4 years of treatment with dasatinib. The complete remission of pulmonary arterial hypertension following dasatinib discontinuation suggests an etiological role of the drug in its development, although the administration of sildenafil may have played a therapeutic role.