Background: Although echocardiography-derived tricuspid regurgitant jet velocity (TRV) is associated with increased mortality in sickle-cell disease (SCD), it is unclear whether increased TRV is a marker of multiorgan disease due to systemic vasculopathy or related to increased pulmonary artery systolic pressure with episodes of multiple acute chest syndrome (ACS). Methods: Our study analyzed 148 consecutive patients with transthoracic echocardiography with TRV data, who came to our adult SCD Clinic at the Wake Forest Baptist Medical Center. For our analysis, we took TRV ≥2.5 m/s as elevated. Patients were followed on average for 9 years. Results: TRV ≥3 m/s was significantly associated with increased mortality (p < 0.001), thromboembolism (p < 0.001), hospitalization for ACS (p < 0.001), supraventricular arrhythmia (p = 0.028), right ventricular (RV) dilation, decreased hemoglobin and increased creatinine. Patients with a progressive increase in TRV during follow-up had increased mortality (36.7 vs. 8.6%, p = 0.007) and increased ACS (45 vs. 5.7%, p < 0.001). Death was independently associated with TRV ≥3 m/s (p = 0.023), ACS (p = 0.001) and increased RV basal diameter (p = 0.003). Conclusions: TRV is an important global marker for the severity and progression of SCD, and carries a significant prognostic implication.

Castro O, Hoque M, Brown BD: Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival. Blood 2003;101:1257-1261.
Collins FS, Orringer EP: Pulmonary hypertension and cor pulmonale in the sickle hemoglobinopathies. Am J Med 1982;73:814-821.
Anthi A, Machado RF, Jison ML, Taveira-Dasilva AM, Rubin LJ, Hunter L, Hunter CJ, Coles W, Nichols J, Avila NA, Sachdev V, Chen CC, Gladwin MT: Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension. Am J Respir Crit Care Med 2007;175:1272-1279.
Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP: Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004;350:886-895.
Ataga KI, Sood N, De Gent G, Kelly E, Henderson AG, Jones S, Strayhorn D, Lail A, Lieff S, Orringer EP: Pulmonary hypertension in sickle cell disease. Am J Med 2004;117:665-669.
Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaïci A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G: A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 2011;365:44-53.
Fonseca GH, Souza R, Salemi VM, Jardim CV, Gualandro SF: Pulmonary hypertension diagnosed by right heart catheterisation in sickle cell disease. Eur Respir J 2012;39:112-118.
Mehari A, Gladwin MT, Tian X, Machado RF, Kato GJ: Mortality in adults with sickle cell disease and pulmonary hypertension. JAMA 2012;307:1254-1256.
Ataga KI, Moore CG, Jones S, Olajide O, Strayhorn D, Hinderliter A, Orringer EP: Pulmonary hypertension in patients with sickle cell disease: a longitudinal study. Br J Haematol 2006;134:109-115.
De Castro LM, Jonassaint JC, Graham FL, Ashley Koch A, Telen MJ: Pulmonary hypertension associated with sickle cell disease: clinical and laboratory endpoints and disease outcomes. Am J Hematol 2008;83:19-25.
Du ZD, Roguin N, Milgram E, Saab K, Koren A: Pulmonary hypertension in patients with thalassemia major. Am Heart J 1997;134:532-537.
Verresen D, De Backer W, Van Meerbeeck J, Neetens I, Van Marck E, Vermeire P: Spherocytosis and pulmonary hypertension coincidental occurrence or causal relationship? Eur Respir J 1991;4:629-631.
Heller PG, Grinberg AR, Lencioni M, Molina MM, Roncoroni AJ: Pulmonary hypertension in paroxysmal nocturnal hemoglobinuria. Chest 1992;102:642-643.
Powars D, Weidman J, Odom-Maryon T, Niland JC, Johnson C: Sickle cell chronic lung disease: prior morbidity and the risk of pulmonary failure. Medicine 1988;67:66-76.
Pianosi P, D'Souza SJ, Charge TD, Esseltine DE, Coates AL: Pulmonary function abnormalities in childhood sickle cell disease. J Pediatr 1993;122:366-371.
Koumbourlis AC, Zar HJ, Hurlet-Jensen A, Goldberg MR: Prevalence and reversibility of lower airway obstruction in children with sickle cell disease. J Pediatr 2001;138:188-192.
Siddiqui AK, Ahmed S: Pulmonary manifestations of sickle cell disease. Postgrad Med J 2003;79:384-390.
Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ: Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. JACC 2005;18:1440-1463.
Devereux R, Alonso D, Lutas E, Gottlieb GJ, Campo E, Sachs I, Reichek N: Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450-458.
Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB: Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685-713.
Nishimura RA, Tajik AJ: Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician's Rosetta Stone. J Am Coll Cardiol 1997;30:8-18.
Kasner M, Westermann D, Steendijk P, Gaub R, Wilkenshoff U, Weitmann K, Hoffmann W, Poller W, Schultheiss HP, Pauschinger M, Tschöpe C: Utility of Doppler echocardiography and tissue Doppler imaging in the estimation of diastolic function in heart failure with normal ejection fraction: a comparative Doppler-conductance catheterization study. Circulation 2007;11:637-647.
Ambrusko SJ, Gunawardena S, Sakara A, Windsor B, Lanford L, Michelson P, Krishnamurti L: Elevation of tricuspid regurgitant jet velocity, a marker for pulmonary hypertension in children with sickle cell disease. Pediatr Blood Cancer 2006;47:907-913.
Nelson SC, Adade BB, McDonough EA, Moquist KL, Hennessy JM: High prevalence of pulmonary hypertension in children with sickle cell disease. J Pediatr Hematol Oncol 2007;29:334-337.
Hagar RW, Michlitsch, JG, Gardner J, Vichinsky EP, Morris CR: Clinical differences between children and adults with pulmonary hypertension and sickle cell disease. Br J Haematol 2008;140:104-112.
Minniti CP, Sable C, Campbell A, Rana S, Ensing G, Dham N, Onyekwere O, Nouraie M, Kato GJ, Gladwin MT, Castro OL, Gordeuk VR: Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation. Haematologica 2009;94:340-347.
Colombatti R, Maschietto N, Varotto E, Grison A, Grazzina N, Meneghello L, Teso S, Carli M, Milanesi O, Sainati L: Pulmonary hypertension in sickle cell disease children under 10 years of age. Br J Haematol 2010;5:601-609.
Bhalla M, Abboud MR, McLoud TC, Shepard JA, Munden MM, Jackson SM, Beaty JR, Laver JH: Acute chest syndrome in sickle cell disease: CT evidence of microvascular occlusion. Radiology 1993;187:45-49.
Emre U, Miller ST, Guitierez M, Steiner P, Rao SP, Rao M: Effect of transfusion in acute chest syndrome of sickle cell disease. J Pediatr 1995;127:901-904.
Gladwin MT, Vichinsky E: Pulmonary complications of sickle cell disease. N Engl J Med 2008;359:2254-2265.
Shubin J, Kaufman R, Shapiro M, Levinson DC: Cardiovascular findings in children with sickle cell anemia. Am J Cardiol 1960;6:875-885.
Oppenheimer EH, Esterly JR: Pulmonary changes in sickle cell disease. Am Rev Respir Dis 1971;103:858-859.
Bowen EF, Crowston JG, De Ceulaer K, Serjeant GR: Peak expiratory flow rate and the acute chest syndrome in homozygous sickle cell disease. Arch Dis Child 1991;66:330-332.
Charache S: Sickle cells and sudden death. J Lab Clin Med 1994;124:473-474.
Reiter CD, Wang X, Tanus-Santos JE, Hogg N, Cannon RO 3rd, Schechter AN, Gladwin MT: Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nat Med 2002;8:1383-1389.
Morris CR, Kuypers FA, Larkin S, Vichinsky EP, Styles LA: Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol 2000;22:515-520.
Morris CR, Morris SM Jr, Hagar W, Van Warmerdam J, Claster S, Kepka-Lenhart D, Machado L, Kuypers FA, Vichinsky EP: Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med 2003;168:63-69.
Aslan M, Ryan TM, Adler B, Townes TM, Parks DA, Thompson JA, Tousson A, Gladwin MT, Patel RP, Tarpey MM, Batinic-Haberle I, White CR, Freeman BA: Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci USA 2001;98:15215-15220.
Gladwin MT, Schechter AN, Ognibene FP, Coles WA, Reiter CD, Schenke WH, Csako G, Waclawiw MA, Panza JA, Cannon RO 3rd: Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation 2003;107:271-278.
Rother RP, Bell L, Hillmen P, Gladwin MT: The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 2005;293:1653-1662.
Gladwin MT, Kato GJ: Cardiopulmonary complications of sickle cell disease: role of nitric oxide and hemolytic anemia. Hematology Am Soc Hematol Educ Program 2005;51-57.
D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT: Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med 1991;115:343-349.
McLaughlin VV, Sitbon O, Badesch DB, Barst RJ, Black C, Galiè N, Rainisio M, Simonneau G, Rubin LJ: Survival with first-line bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005;25:244-249.
Sandoval J, Baurle O, Palomar A, Martinez-Guerra ML, Beltran M, Guerrero L: Survival in primary pulmonary hypertension: validation of a prognostic equation. Circulation 1994;89:1733-1744.
Chin KM, Nick HS, Rubin LJ: The right ventricle in pulmonary hypertension. Coron Art Dis 2005;16:13-18.
Lewis JF, Webber JD, Sutton LL, Chesoni S, Curry CL: Discordance in degree of right and left ventricular dilation in patients with dilated cardiomyopathy: recognition and clinical implications. J Am Coll Cardiol 1993;21:649-654.
Sullivan KJ, Goodwin SR, Evangelist J: Successful use of nitric oxide to treat severe acute chest syndrome in sickle cell disease. Crit Care Med 1999;27:2563-2568.
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