Elevated Tricuspid Regurgitation Velocity Research Articles

Lipid levels in sickle‐cell disease associated with haemolytic severity, vascular dysfunction and pulmonary hypertension

Pulmonary hypertension (PH) in sickle cell disease (SCD) is an emerging and important clinical problem. In a single-institution adult cohort of 365 patients, we investigated lipid and lipoprotein levels and their relationship to markers of intravascular haemolysis, vascular dysfunction and PH. In agreement with prior studies, we confirm significantly decreased plasma levels of total cholesterol, high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C) in SCD versus ethnically-matched healthy controls. Several cholesterol parameters correlated significantly with markers of anaemia, but not endothelial activation or PH. More importantly, serum triglyceride levels were significantly elevated in SCD compared to controls. Elevated triglyceride levels correlated significantly with markers of haemolysis (lactate dehydrogenase and arginase; both P < 0.0005), endothelial activation (soluble E-selectin, P < 0.0001; soluble P-selectin, P = 0.02; soluble vascular cell adhesion molecule-1, P = 0.01), inflammation (leucocyte count, P = 0.0004; erythrocyte sedimentation rate, P = 0.02) and PH (amino-terminal brain natriuretic peptide, P = 0.002; prevalence of elevated tricuspid regurgitant velocity (TRV), P < 0.001). In a multivariate analysis, triglyceride levels correlated independently with elevated TRV (P = 0.002). Finally, forearm blood flow studies in adult patients with SCD demonstrated a significant association between increased triglyceride/HDL-C ratio and endothelial dysfunction (P < 0.05). These results characterize elevated plasma triglyceride levels as a potential risk factor for PH in SCD.

Angiogenic and Inflammatory Markers of Cardiopulmonary Changes in Children and Adolescents with Sickle Cell Disease

BackgroundPulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well.Design and MethodsPlasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor–BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined.ResultsPlasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P≤0.003). By logistic regression, greater values for PDGF-BB (P = 0.009), interleukin-6 (P = 0.019) and the hemolytic component (P = 0.026) were independently associated with increased odds of elevated tricuspid regurgitation velocity while higher VEGF concentrations were associated with decreased odds (P = 0.005) among the patients with sickle cell disease. These findings, which are consistent with reports that PDGF-BB stimulates and VEGF inhibits vascular smooth muscle cell proliferation, did not apply to E/Etdi.ConclusionsCirculating concentrations of angiogenic and pro-Inflammatory markers are altered in sickle cell disease children and adolescents with elevated tricuspid regurgitation velocity, a subgroup that may be at risk for developing worsening pulmonary hypertension. Further studies to understand the molecular changes in these children are indicated.

Hemolysis-Associated Elevation in Tricuspid Regurgitation Velocity Predicts Reduction in Six-Minute Walk Distance After Two Years of Follow up in Children and Adolescents with Sickle Cell Disease.

Abstract 574 Background.Elevated tricuspid regurgitation velocity (TRV) as determined by echocardiography correlates with elevated systolic pulmonary artery pressure and is associated with increased morbidity and mortality in adults with sickle cell disease. The importance of elevated TRV in children and adolescents with sickle cell disease is not known. The Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study is an ongoing, longitudinal and observational multicenter study of children with sickle cell disease. Methods.Baseline echocardiography and six-minute walk test were performed prospectively in 361 children and adolescents with sickle cell disease at steady state and then repeat studies were performed in 209 after a median of 22 months of follow up (range 10 months to 36 months), also at steady state. A hemolytic component was derived by principal component analysis of baseline values for reticulocyte count, lactate dehydrogenase, aspartate aminotransferase and total bilirubin. Results.TRV or six-minute walk test were measured at both baseline and follow-up in 193 patients. Twenty-one of these 193 patients had elevated TRV of 2.60 m/sec or higher at baseline. Elevated baseline TRV was associated with high hemolytic rate in 15 patients, defined as hemolytic component above the median for the population studied, and with lower hemolytic rate in six patients. Elevated baseline TRV with high hemolytic rate predicted elevated TRV at follow up (odds ratio 7.7; 95% confidence interval [CI] 2.5 to 24.2; P <0.001) but elevated baseline TRV with lower hemolytic rate did not (odds ratio 1.6; 95% CI 0.2 to 14.1; P = 0.7). Elevated baseline TRV with high hemolytic rate also predicted a decline in the six-minute walk distance by 10% or more at follow-up (hazard ratio 3.9; 95% CI 1.4 to 10.7; P = 0.009). In contrast, higher cardiac output as measured by the left ventricular end diastolic dimension z-score was associated with reduced risk for a decline in the walk distance (hazard ratio 0.7; 95%CI 0.6 to 0.9; P = 0.006). Conclusion.Steady-state TRV elevation in association with a high hemolytic rate occurs on screening in about 8% of children and adolescents with sickle cell disease and is predictive of elevated TRV and reduced six-minute walk distance after approximately two years of follow. Such children may be at risk for adverse clinical consequences of pulmonary hypertension as young adults. Further studies are indicated to identify the molecular mechanisms and to develop appropriate medical management for children and adolescents with this complication. Disclosures:No relevant conflicts of interest to declare.

Prospective Echocardiography Assessment of Pulmonary Hypertension and Its Potential Etiologies in Children With Sickle Cell Disease

Pulmonary hypertension (PH) is associated with adverse outcomes in adults with sickle-cell disease (SCD), but its importance in children is less clear. The aim of this study was to define the incidence and causes of PH in pediatric patients with SCD. Children with SCD (n = 310) and matched controls (n = 54) were prospectively enrolled under basal conditions. Participants underwent echocardiography, pulse oximetry, 6-minute walk tests, and hematologic testing. Echocardiographic measures were compared between patients with SCD and control subjects before and after adjusting for hemoglobin. Correlations of echocardiographic and clinical parameters were determined. Tricuspid regurgitation velocity (TRV) was elevated compared to controls (2.28 vs 2.10 m/s, p <0.0001). Increased TRV was associated with left ventricular diastolic diameter, hemoglobin, and estimated left atrial pressure. TRV remained elevated when controlling for left ventricular diameter and left atrial pressure. Echocardiographically derived pulmonary resistance was not significantly different between patients with SCD and controls, although it was elevated in the SCD subgroup with elevated TRV. When controlling for hemoglobin, TRV was no longer statistically different, but pulmonary insufficiency velocity, septal wall thickness, and estimated pulmonary resistance were statistically higher. TRV, pulmonary insufficiency end-diastolic velocity, and markers of increased cardiac output were correlated with indicators of adverse functional status, including history of acute chest syndrome, stroke, transfusions, and 6-minute walk distance. In conclusion, children with SCD had mildly increased TRV that was correlated with increased cardiac output and left ventricular filling pressures. Hemoglobin-adjusted analysis also suggested a contribution of primary vascular changes.

Echocardiographic findings in patients with sickle cell disease

Pulmonary hypertension is a complication of sickle cell disease that is associated with increased mortality. Whether this complication is associated with hemolysis has been questioned. Systolic pulmonary artery blood pressure can be estimated from echocardiography-determined tricuspid regurgitation velocity (TRV). A velocity of 2.5 m/s or higher suggests possible pulmonary hypertension. A retrospective review of hospital records from adult patients with sickle cell disease undergoing echocardiography in 2006 and 2007 was performed at a tertiary level hospital. Echocardiographic, demographic, and clinical laboratory data were collected. Echocardiographic results were available for 105 adult sickle cell patients. Of these, 62 (59%) had a TRV ≥2.5 m/s and 24 (22.8%) had a TRV ≥3.0 m/s. Mitral valve regurgitation was observed in 44% and left ventricular abnormalities (defined by either hypertrophy or dilation) in 28% of cases. Elevated TRV had independent and significant associations with greater age, higher serum lactate dehydrogenase (LDH) concentration, and lower hemoglobin concentration. We confirmed that elevated TRV is common among hospital-based adults with sickle cell disease. Significant, independent associations were found with both elevated LDH concentration and degree of anemia, suggesting that hemolytic and other mechanisms contribute to pulmonary hypertension in patients with sickle cell disease.

Elevation of tricuspid regurgitant jet velocity, a marker for pulmonary hypertension in children with sickle cell disease

Pulmonary hypertension (PHTN) is a potentially life-threatening complication, detected by echocardiographic evidence of elevated tricuspid regurgitant velocity (TRV). This condition has been described in adults with sickle cell disease (SCD) and other hemolytic disorders; however, there is little information on the occurrence of this condition in pediatric patients. Records for pediatric SCD patients were retrospectively reviewed to determine clinical characteristics and co-morbidities of patients with elevated TRV on echocardiograms obtained under steady state conditions as an outpatient. Correlation of TRV > or =2.5 m/sec with age, sex, type of SCD, number of outpatient echocardiograms per patient, episodes of vasoocclusive crisis (VOC) and acute chest syndrome (ACS), mean hemoglobin and reticulocyte count, asthma, obstructive sleep apnea, cerebrovascular disease (CVD), and hydroxyurea therapy was determined. Of 224 SCD patients, 44 had outpatient echocardiographic measurement of TRV. Patients (11 of 44) (26.2%) with TRV > or =2.5 m/sec were compared to 31 patients without elevated TRV. Significant differences were noted for percent with HbSS disease (P = 0.041), CVD (P = 0.021), hemoglobin (P = 0.003), % reticulocytes (P = 0.037), and number of echocardiograms performed (P < 0.001). No significant differences were observed for gender, age, asthma, or frequency of VOC and ACS. Elevated TRV, a surrogate marker for PHTN, occurs in children with SCD and is associated with low hemoglobin, elevated reticulocyte count, and cerebral vasculopathy. Appropriate screening by echocardiography can lead to detection and treatment that may reduce TRV and potentially reverse the disease process, prevent the increased morbidity and mortality associated with PHTN.