Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom

• Published in: Circulation (New York, N.Y.) Vol. 124; no. 13; pp. 1452 - 1460
• Main Authors: Sachdev, Vandana, Kato, Gregory J., Gibbs, J. Simon R., Barst, Robyn J., Machado, Roberto F., Nouraie, Mehdi, Hassell, Kathryn L., Little, Jane A., Schraufnagel, Dean E., Krishnamurti, Lakshmanan, Novelli, Enrico M., Girgis, Reda E., Morris, Claudia R., Rosenzweig, Erika Berman, Badesch, David B., Lanzkron, Sophie, Castro, Oswaldo L., Taylor, James G., Hannoush, Hwaida, Goldsmith, Jonathan C., Gladwin, Mark T., Gordeuk, Victor R.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 27.09.2011
• Subjects: Adolescent; Adult; Aged; Anemia, Sickle Cell - genetics; Anemia, Sickle Cell - mortality; Anemia, Sickle Cell - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Child; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Echocardiography; Exercise Test - methods; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; Fundamental and applied biological sciences. Psychology; Homozygote; Humans; Hypertension, Pulmonary - diagnostic imaging; Hypertension, Pulmonary - mortality; Hypertension, Pulmonary - physiopathology; Male; Medical sciences; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Pulmonary Artery - diagnostic imaging; Tricuspid Valve Insufficiency - diagnostic imaging; Tricuspid Valve Insufficiency - mortality; Tricuspid Valve Insufficiency - physiopathology; United Kingdom; United States; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - mortality; Ventricular Dysfunction, Left - physiopathology; Vertebrates: cardiovascular system; Young Adult; United Kingdom; United States; North America; Europe; America; Heart; Physical exercise; Sickle cell anemia; Diastolic pressure; Diastole; Cardiovascular disease; Heart ventricle; exercise; Hemopathy; Left ventricular failure; Homozygosity; Hemolytic anemia; Heart disease; Left ventricle performance; Human; Hypertension; Hemoglobinopathy; Echocardiography; pulmonary; anemia; Genetic disease; Intolerance; Adolescent; sickle cell; Circulatory system
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.111.032920

Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults with sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively. Echocardiography, 6-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the U.S. and U.K. Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid regurgitation velocity, which reflects systolic pulmonary artery pressure, was 2.7 to <3.0 m/s (mean±SD, 2.8±0.1) in 26% of the subjects and ≥3.0 m/s (mean±SD, 3.4±0.4) in 11%. The LV lateral E/e' ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in sickle cell disease, was significantly higher in the groups with tricuspid regurgitation velocity ≥2.7 m/s. Increased hemolysis (P<0.0001), LV lateral E/e' ratio (P=0.0001), blood urea nitrogen (P=0.0002), and erythropoietin (P=0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex (P<0.0001), older age (P<0.0001), LV lateral E/e' ratio (P=0.014), and tricuspid regurgitation velocity (P=0.019) were independent predictors of a shorter 6-minute walk distance. Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e' ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LV diastolic dysfunction will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00492531.