Heart Disease in Sickle Cell Anemia
Palabras clave
Abstracto
Descripción
Sickle cell anemia is an inherited blood disorder primarily affecting groups with origins in endemic malarial areas, especially those of African descent. SCA results from one of two single amino-acid substitutions in beta-hemoglobin (Hb-S and Hb-C) that increases the propensity for hemoglobin to polymerize, thus distorting, sickling and hemolyzing red cells. Individuals homozygous for Hb-S (or double heterozygote Hb-S and Hb-C) develop sickle cell anemia (SCA), while heterozygotes have sickle cell trait. SCA is characterized by chronic anemia and crises of red cell sickling and ischemia that are often painful and affect several organs and tissue types. SCA confers considerable disability, morbidity and mortality.
Annual mortality from SCA has been estimated at approximately 3%. As a significant number of these deaths are sudden, a cardiac cause has been suspected. However, no cardiac mechanism of sudden death (SD) has been clearly identified. Recently, it has been demonstrated that SCA patients with pulmonary hypertension (PAH) have a higher incidence of SD than those with normal pulmonary pressures. In many patients, PAH occurs in association with elevated pulmonary arterial wedge pressures and normal pulmonary arterial resistance, suggesting that the PAH develops as the result of left ventricular (LV) abnormalities. Furthermore, in other conditions in which PAH develops, SD occurs only at pressures considerably higher than those observed in SCA. These factors suggest that PAH in SCA is a surrogate marker for, rather than the cause of SD. Rather, an SCA cardiomyopathic process may provide a unifying mechanism that associates moderate degrees of PAH and high risk of SD from cardiac causes.
We propose to describe the extent of cardiac involvement in SCA. Specifically, we will (1) describe the LV volume-pressure relations in SCA patients with and without pulmonary hypertension in order to determine how elevated pulmonary pressures are related to dynamic filling properties of the LV; and (2) determine whether cardiac arrhythmias are common in SCA patients with PAH and if they contribute to SD.
Improved understanding of the etiology and mechanisms of SD in SCA may allow the development and testing of therapies for the primary prevention of SD.
fechas
| Verificado por última vez: | 10/01/2007 |
| Primero enviado: | 06/02/2005 |
| Inscripción estimada enviada: | 06/02/2005 |
| Publicado por primera vez: | 06/05/2005 |
| Última actualización enviada: | 06/29/2017 |
| Última actualización publicada: | 07/01/2017 |
| Fecha de inicio real del estudio: | 06/01/2005 |
| Fecha estimada de finalización del estudio: | 10/01/2007 |
Condición o enfermedad
Fase
Criterio de elegibilidad
| Edades elegibles para estudiar | 18 Years A 18 Years |
| Sexos elegibles para estudiar | All |
| Acepta voluntarios saludables | si |
| Criterios | - INCLUSION CRITERIA FOR RIGHT HEART CATHETERIZATION AND STRESS ECHO: 1. Either gender, aged greater than 18 years 2. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S Beta-thalassemia genotype is required) 3. Hematocrit greater than 18 % (with an absolute reticulocyte count greater than 100,000/ml) EXCLUSION CRITERIA FOR RIGHT HEART CATHETERIZATION AND STRESS ECHO: 1. Pregnancy or lactation 2. Known or suspected coronary artery disease 3. Hematocrit less than 18 %: will not be eligible for the study; may return for evaluation at a later date 4. Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30% of normal 5. Cerebrovascular accident within the last six weeks 6. New diagnosis of pulmonary embolism within the last three months 7. History of retinal detachment 8. Patients with PAH known to be secondary to other causes, such as systemic lupus erythematosus, other collagen vascular diseases, valvular heart disease, congenital heart disease 9. Poor echo windows 10. Any other condition that would prevent participation in the study (for example HIV infection) INCLUSION CRITERIA FOR NON-INVASIVE PROCEDURES: 1. Either gender, aged greater than 18 years 2. Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S Beta-thalassemia genotype is required) EXCLUSION CRITERIA FOR NON-INVASIVE PROCEDURES: 1. Pregnancy or lactation 2. Known or suspected coronary artery disease 3. Significant renal insufficiency (patient on hemodialysis or estimated creatinine clearance less than 30%of normal 4. Cerebrovascular accident within the last six weeks 5. New diagnosis of pulmonary embolism within the last three months 6. History of retinal detachment 7. Patients with PAH known to be secondary to other causes, such as systemic lupus erythematosus, other collagen vascular diseases, valvular heart disease, congenital heart disease 8. Patients who are intolerant of MRI will not undergo cardiac MRI 9. Any other condition that would prevent participation in the study (for example HIV infection) |
