Pulmonary Hypertension, Tricuspid Regurgitant Velocity Screening, and the Nitric Oxide Pathway

Abstract

Chronic pulmonary complications, including pulmonary hypertension (PH), are common in sickle cell disease (SCD), especially in adults with sickle cell anemia (SCA). The underlying pathophysiology is complex and variable, involving multiple biological systems. Recent emphasis has been placed on the pleotropic biological factor nitric oxide (NO). An elevated tricuspid regurgitant velocity (TRV) appears to have limitations in specificity in SCA, but may indicate the presence of PH, a diagnosis confirmed by right heart catheterization. TRV has been used in recent clinical trials to identify or define subjects with PH for enrollment into PH-specific interventions; these include sildenafil, which enhances NO-induced vasorelaxation. Results from a controlled trial show no benefit and an unexpected increase in adverse events, emphasizing the biological complexities of SCA. Management remains principally supportive, includes recognition and treatment of comorbidities, and may incorporate individualized PH-specific strategies (despite recent trials) based on appropriate diagnostic testing. Ultimately, therapy is likely to be multimodal and tailored to the processes identified to be the most contributory in a given individual. Based on the relative prevalence of the conditions, routine screening for asthma in children with SCD and by Doppler echocardiography to measure TRV as an initial screen for PH in adults with SCA may be warranted. Data are limited regarding the clinical utility of screening in other forms of SCD and the pediatric population. This article offers an individual perspective on practical and challenging clinical considerations.

Pulmonary hypertension in sickle cell disease: diagnosis and management

“…49 Screening for PH in patients with SCD remains controversial. 16,50 To be appropriate for screening, a disease must be serious and have severe consequences, must be progressive so that early treatment is more effective than later treatment, must have a preclinical phase that can be identified by a screening test, and must have a preclinical phase that is fairly long and prevalent in the target population. 49 There is abundant evidence that echocardiography-derived TRV Ն2.5 m/s, as well as PH confirmed on RHC, are associated with an increased risk of death in adult patients with SCD, 11,[18][19][20][21]30,31 confirming the serious nature of these pulmonary vasculopathies.…”

Ruxolitinib leads to improvement of pulmonary hypertension in patients with myelofibrosis

“…4-7 PH manifests with nonspecific symptoms such as dyspnea on exertion and fatigue and can be detected by showing elevated right ventricular systolic pressure (RVSP)435 mm Hg, right atrium enlargement and tricuspid regurgitation velocity X2.5 m/s using echocardiography. 8,9 As PH progresses, patients can develop peripheral edema, jugular vein distention, exertional dyspnea, chest discomfort and eventually right heart failure. 10,11 According to the World Health Organization, PH can be further classified into five subtypes.…”

Elevated tricuspid regurgitant jet velocity in subgroups of thalassemia patients: insight into pathophysiology and the effect of splenectomy

“…However, in other 3 patients, transfusions have not reversed the increased TRV, suggesting the development of irreversible vasculature changes in the lung tissue [24], when instituted at later stages of evolving PH. The frequency and level of Hb required to prevent the pathophysiological changes resulting in an increase of TRV in TI patients who are not regularly transfused has not been studied.…”