Risk factors and mortality associated with an elevated tricuspid regurgitant jet velocity measured by Doppler-echocardiography in thalassemia: a Thalassemia Clinical Research Network report

Abstract

IntroductionPulmonary hypertension (PH) is emerging as a significant cause of mortality and morbidity in patients with hemolytic anemias. 1,2 Mortality rates associated with PH are universally high in conditions in which the natural history has been established, including sickle cell disease (SCD), 3,4 scleroderma and other connective tissue diseases, chronic obstructive lung disease, thromboembolic disorders, and idiopathic pulmonary artery hypertension. 5 Although the frequent occurrence of PH has been recognized in both thalassemia intermedia (TI) and major (TM) for some time, 1,6-14 the natural history and mortality risk of this comorbidity in the thalassemia syndromes has yet to be established, and prospective longitudinal studies are limited. Prevalence rates vary by study design with an elevated tricuspid regurgitant jet velocity (TRV) noninvasively measured by Doppler echocardiography (echo), suggesting risk for PH detected in up to 75% in some cohorts. 15,16 Although the high prevalence of PH in nontransfused TI patients has now been well documented, 14,16,17 PH risk was established in Ͼ 50% of patients with ␤-thalassemia major despite transfusion. 6,17,18 In another study of TM, pulmonary systolic pressure Ͼ 30 mm/Hg was found in all patients Ͼ 22 years of age. 6 However, recent studies in more uniformly treated patients have shown a lower frequency of PH risk in TM patients who undergo transfusion regularly. 7,12 The etiology of PH in thalassemia is multifactorial, involving a complex interaction of platelets, the coagulation system, erythrocytes, and endothelial cells along with inflammatory and vascular mediators. 13,19 Contributing mechanisms include oxidative stress, 20 hemolysis, 21,22 thrombosis, 23-25 splenectomy, 17,22,26 abnormal arginine-nitric oxide bioavailability, 13,21 red cell membrane pathology, 27 and iron overload. 28 Although overlap in pathways contributing to vasculopathy and PH is expected in all forms of thalassemia, 13 the pathophysiology of PH is fundamentally different in patients with TI compared with TM. Hemolysis is likely a driving force toward PH in nontransfused TI patients, whereas the consequences of iron overload and oxidative stress may play a more significant role in TM patients receiving transfusion therapy. 19 Autopsy studies in patients with thalassemia revealed histopathologic findings that are common to all forms of PH, including plexiform and concentric medial hyperplastic pulmonary vascular lesions, and in situ pulmonary artery thrombosis. 29 However, despite multiple similarities with pulmonary artery hypertension of various etiologies, PH in hemolytic disease is a unique disorder that differs from other forms Submitted November 29, 2010; accepted July 1, 2011. Prepublished online as Blood First Edition paper, July 19, 2011; DOI 10.1182 DOI 10. /blood-2010 An Inside Blood analysis of this article appears at the front of this issue.The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by pa...

Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

“…Screening for PH was performed by the non-invasive Doppler echocardiography with different modalities using Vivid E9 (GE Healthcare, Oslo, Norway) to evaluate right and left ventricle function, pulmonary artery pressure and tricuspid regurgitant jet velocity (TRV). A TRV ≥2.5 m/s was used as a proxy for patients at risk for PH [30,31]. Heart disease was defined by at systolic left ventricle (LV) dysfunction (LV shortening fraction <30% or LV ejection fraction < 55%) [32].…”

Response to "Efficacy and safety of sildenafil for the treatment of severe pulmonary hypertension in patients with hemoglobinopathies: results from a long-term follow up " Haematologica 2014;99(2):e17-18.

“…9,14,15 The recent implication of elevated circulating platelet and erythrocyte microparticles in thalassemia patients associated with markers of hemolysis as well as vascular dysfunction, PH risk, and prior splenectomy, 16 reveal an overlap in these potential mechanisms that requires further study.…”

Sildenafil therapy in thalassemia patients with Doppler-defined risk of pulmonary hypertension

“…A TRV ≥2.5 m/s is 2 standard deviations above normal and associated with morbidity in hemoglobinopathies. 3,34 A cut-off of 2.6 m/s was chosen to minimize enrollment of borderline cases. At the time this pilot study was designed, right heart catheterization was not routinely performed in patients with thalassemia and was considered to be "too invasive" by practicing hematologists.…”

“…An elevated tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/s on Doppler echocardiography is a common finding in patients with thalassemia 3 and can identify those at increased risk of PH. However, invasive right heart catheterization is required to make a definitive diagnosis of PH.…”

“…[4][5][6][7][8][9][10] Advancing age and a history of splenectomy are major risk factors for PH in this population. 3,[10][11][12][13] Other risk factors include transfusion-naivety and an elevated nucleated red blood cell count.…”