Oxygen Desaturation at Rest and after Exercise in Pediatric Sickle Cell Disease Patients: Correlations with Hemolysis and Elevated Tricuspid Regurgitant Jet Velocity.

Abstract Background. As a part of a multicenter, observational study in determining the prevalence and risk factors of elevated tricuspid regurgitant jet velocity (TRV) in children, oxygen desaturation correlated with TRV. We further investigated the risk factors and clinical associations of oxygen desaturation at rest and after execrcise in children at steady state. Methods. 310 children and adolescents with sickle cell disease were studied under basal conditions. Pulse oximetry was determined at rest and after a six minute walk test. The relationships of oxygen saturation at rest and desaturation during exercise to the available clinical and laboratory variables were investigated. Results. Among 300 patients with available baseline oxygen saturations, 30 (10%) had saturation <95 percent, 129 (43%) had saturation of 95–98 percent, and 141 (47%) had saturation >98 percent. Twenty-three (9%) of 244 patients had >3 percentage point reduction in oxygen saturation during a six minute walk; the median (interquartile range) baseline saturation was 96 (95– 99) percent among these patients versus 98 (97–100) percent among those with less or no reduction in saturation during the walk (P = 0.0009). Hemoglobin (p<0.0001), creatinine (p=0.014) and total lung capacity (p=0.042) were also lower in patients with declines in saturations >3 percentage points during the walk while a hemolytic index (p<0.0001), tricuspid regurgitant jet velocity (p=0.030), pulmonary insufficiency end diastolic velocity (PIEDV) (p=0.019), left ventricular mass index (LVMI) (p=0.0006) and left ventricular internal diameter z score (LVIDD z score) (p=0.0001) were higher. In 3 separate logistic regression models (clinical variables, echocardiographic parameters, and pulmonary function testing), lower hemoglobin, hemolytic index, PIEDV, LVIDD z score, and low TLC were independent predictors of six-minute-walk desaturation of >3 percentage points. Conclusion. Markers of hemolysis, low hemoglobin, PIEDV, LVMI, LVIDD z score, lower TLC, and elevated TRV velocities are associated with ≥3% reduction in oxygen desaturation during six minute walk in children and adolescents with sickle cell disease. A high degree of oxygen desaturation during the six minute walk in sickle cell disease patients might serve as an early biomarker for pulmonary hypertension. Exercise induced changes in oxygen saturation in sickle cell disease children may provide insight into the development of pulmonary hypertension as adults.

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Elevated tricuspid regurgitant jet velocity in children and adolescents with sickle cell disease: association with hemolysis and hemoglobin oxygen desaturation

Haematologica ◽

10.3324/haematol.13812 ◽

2009 ◽

Vol 94 (3) ◽

pp. 340-347 ◽

Cited By ~ 112

Author(s):

C. P. Minniti ◽

C. Sable ◽

A. Campbell ◽

S. Rana ◽

G. Ensing ◽

...

Keyword(s):

Sickle Cell Disease ◽

Children And Adolescents ◽

Sickle Cell ◽

Disease Association ◽

Oxygen Desaturation ◽

Cell Disease ◽

Jet Velocity ◽

Tricuspid Regurgitant Jet Velocity

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Association of Hemolysis with Clinical Manifestations of Sickle Cell Disease

Blood ◽

10.1182/blood.v112.11.2482.2482 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2482-2482

Author(s):

Mehdi Nouraie ◽

Caterina Minniti ◽

Craig Sable ◽

Andrew D. Campbell ◽

Sohail R Rana ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Manifestations ◽

Hemoglobin Concentration ◽

Left Ventricular ◽

P Value ◽

Z Score ◽

Cell Disease ◽

History Of ◽

Minute Walk

Abstract Background: Sickle cell disease shares common complications such as vasculopathy and organ dysfunction involving the heart, the lungs, the liver and the kidneys with other hemolytic conditions. We hypothesized that a hemolytic vasculopathy may underlie some of these complications. Distinguishing whether a complication is due to hemolysis or to the degree of anemia has been a challenge. Methods: A prospective, multicenter study of 310 children and adolescents with sickle cell disease in steady state was conducted. The associations of measures of hemolysis and of hemoglobin concentration with disease complications were assessed. Principle component analysis was used to develop a hemolytic index from the measurements of reticulocyte count, lactate dehydrogenase, aspartate aminotransfersae and total bilirubin. In order to determine the independent associations of hemolysis with the clinical manifestations of sickle cell disease, we computed correlation coefficient of the hemolytic index with these manifestations that controlled for hemoglobin concentration. P values were adjusted for multiple comparisons. Results: Hemolysis and hemoglobin had no significant correlation with number of the severe pain episodes, acute chest syndrome and priapism. The hemolytic index correlated with history of stroke (r= 0.19, p=0.026), white blood cell count (r=0.22, p<0.001), tricuspid regurgitation velocity (r=0.25, p<0.001), left ventricular mass index (r=0.33, 0<0.001), left ventricular internal diastolic z score (r=0.30, p<0.001) and hemoglobin oxygen desaturation (r=−0.30, p<0.001) but not independently with platelet count and creatinine and six-minute-walk Correlation of clinical outcomes with hemolytic index and hemoglobin concentration in sickle cell cases N Hemolytic index (r and P value) Hemoglobin (r and P value) Hemolytic index adjusted for hemoglobin (partial r and P value) 1 Square roots 2Natural Log 3Adjusted for patient’s height p values are adjusted for 13 comparisons. Number of severe pain episodes in the last year 283 −0.05 (0.4) 0.06 (0.3) −0.02 (0.7) History of acute chest or pneumonia 278 0.11 (0.09) −0.63 (<0.0001) 0.06 (0.3) History of priapism History of stroke 137 0.13 (0.1) −0.63 (<0.0001) 0.06 (0.5) 277 0.14 (0.3) 0.003 (1.0) 0.19 (0.026) Platelet count 1 283 0.32 (<0.0001) −0.35 (<0.0001) 0.11 (0.07) White blood cells 2 283 0.46 (<0.0001) −0.47 (<0.0001) 0.22 (<0.001) Creatinine 1 282 −0.34 (<0.0001) 0.45 (<0.0001) −0.07 (0.2) Systolic blood pressure 283 0.01 (0.8) 0.16 (0.07) 0.14 (0.2) Tricuspid regurgitant jet velocity 264 0.35 (<0.0001) −0.27 (<0.001) 0.25 (<0.001) Left ventricular internal diastolic diameter z score 282 0.53 (<0.0001) −0.50(<0.001) 0.30 (<0.001) Left ventricular mass index1 215 0.51 (<0.0001) −0.44 (<0.001) 0.33 (<0.001) O2 saturation 273 −0.49 (<0.0001) 0.42 (<0.001) −0.30 (<0.001) Six-minute-walk (m)3 228 −0.03 (0.6) 0.17 (0.1) 0.07 (0.3) Conclusion: These observations support the hypothesis that a hemolytic vasculopathy independent of the degree of anemia contributes to the pathogenesis of stroke and pulmonary hypertension and to the development of increased systemic vascular resistance. They also raise the possibility that leukocytosis may in part serve as a predictor of poor outcome by its association with hemolysis. Therapeutic interventions that reduce the rate of hemolysis need to be studied for their potential benefit in decreasing the risk and severity of vasculopathy and the resulting organ damage.

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Pulmonary Hypertension in Sickle Cell Disease: Cardiopulmonary Evaluation and Response to Chronic Phosphodiesterase 5 Inhibitor Therapy.

Blood ◽

10.1182/blood.v104.11.235.235 ◽

2004 ◽

Vol 104 (11) ◽

pp. 235-235 ◽

Cited By ~ 7

Author(s):

Roberto F. Machado ◽

Sabrina E. Martyr ◽

Anastasia Anthi ◽

Gregory J. Kato ◽

Lori A. Hunter ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Functional Capacity ◽

Cell Disease ◽

Walk Distance ◽

Jet Velocity ◽

Minute Walk Distance ◽

Minute Walk ◽

Tricuspid Regurgitant Jet Velocity

Abstract Pulmonary hypertension (PH) is a risk factor for mortality in Sickle Cell Disease, but it is unclear whether pulmonary hypertension is a marker or a direct cause of mortality. To better understand the pathophysiology of pulmonary hypertension in patients with sickle cell disease we performed evaluations of cardiopulmonary function in sickle cell disease patients with pulmonary hypertension (n= 15, mean age = 41 ± 2.4 years, males = 7, HbSS = 15, mean Hb = 8.3 ± 0.2 g/dl, mean tricuspid regurgitant jet velocity = 3.2 ± 0.11 m/s) compared to matched controls with sickle cell disease without pulmonary hypertension (n=11, mean age=40.2 ± 2.5 years, males=4, HbSS=11, mean Hb=8.5 ± 0.3 g/dl, mean tricuspid regurgitant jet velocity = 2.28 ± 0.07 m/s). To evaluate if specific therapy for pulmonary hypertension has any impact on systolic pulmonary artery pressure (PAP), estimated by tricuspid regurgitant jet velocity (TRJ), and functional capacity, measured by six-minute walk test (a well validated surrogate of functional capacity and response to therapy in patients with other causes of pulmonary hypertension), we treated 14 patients with sickle cell disease and pulmonary hypertension (mean age = 40 ± 2.5 years, males = 3, HbSS = 14, mean Hb = 8.8 ± 0.6 g/dl, mean TRJ = 3.4 ± 0.1 m/s) with sildenafil for at least three months. When compared to controls pulmonary hypertension patients had lower maximal oxygen consumption (VO2 max (% predicted), +PH: 44 ± 4, −PH: 55 ± 4; P=0.41), walked shorter six-minute walk distance (meters, +PH: 308.5 ± 53.8, −PH: 427.1 ± 44.6; P=0.03), demonstrated greater degree of interstitial lung disease by chest CT (P < 0.05), and more perfusion impairments measured by ventilation perfusion scan (P < 0.05). Six-minute walk distance correlated directly with maximal oxygen consumption (R=0.6; P=0.01), and inversely with mean pulmonary arterial pressure (R= −0.5; P=0.03) and tricuspid regurgitant jet velocity (R= −0.6;P=0.002), suggesting that the test is an adequate surrogate of functional capacity and response to therapy in pulmonary hypertension patients with sickle cell disease. Chronic treatment with sildenafil (up to 100 mg TID) decreased pulmonary arterial pressure (PAP mmHg, baseline: 50 ± 4.4, sildenafil: 41 ± 2.5; P=0.04) and increased six-minute walk distance (meters, baseline: 394 ± 31, sildenafil: 476 ± 26: P= 0.02). Sildenafil was well tolerated with only 2 patients stopping the drug due to headaches. We also observed 3 episodes of transient eyelid edema not requiring discontinuation of drug. Priapism was not observed in the 3 males treated (2 on exchange transfusion therapy, 1 with erectile dysfunction). In conclusion, we find that in patients with sickle cell disease, 1) pulmonary hypertension, though relatively mild, is associated with severe impairments in cardiopulmonary function, 2) traditional markers of functional capacity such as six-minute walk test can be utilized in this population as a therapeutic endpoint for clinical trials, 3) and therapy with sildenafil seems to have a favorable impact on pulmonary pressures and functional capacity.

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Splenectomy Is Not Associated With Higher Tricuspid Regurgitant Jet Velocity In Patients With Sickle Cell Disease

Blood ◽

10.1182/blood.v122.21.1002.1002 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1002-1002

Author(s):

Tanvi Adsumilli ◽

Hillel Cohen ◽

Jane A. Little ◽

Deepa Manwani

Keyword(s):

Sickle Cell Disease ◽

Linear Regression ◽

Sickle Cell ◽

Categorical Variables ◽

Cell Disease ◽

Walk Distance ◽

Jet Velocity ◽

Minute Walk Distance ◽

Minute Walk ◽

Tricuspid Regurgitant Jet Velocity

Abstract Introduction An elevated tricuspid regurgitant jet velocity (TRV) has been associated with hemolysis and increased mortality in sickle cell disease (SCD). An elevated TRV is also associated with decreased exercise capacity as measured with the six minute walk distance (6MWD). Vascular complications including pulmonary arterial hypertension (PAH) and thrombosis have been reported to occur at an increased rate following splenectomy in various disorders, including chronic hemolytic anemias or those associated with ineffective erythropoiesis, such as thalassemia. The risk of elevated TRV, already high in patients with thalassemia (33%), is significantly increased with splenectomy (unadjusted O.R 5.3, 95% CI 2.1-13.5). We wanted to evaluate the independent association of splenectomy with TRV in a cohort of patients with homozygous SS disease (HbSS). Methods We performed a retrospective cross sectional analysis of the association between splenectomy and an elevated TRV. 41 splenectomized HbSS patients were identified within the 482 HbSS patients ≥12 years of age from the multi-centered Walk-PHASTT study of pulmonary hypertension; this study incorporated a cardiovascular phenotype, including echocardiogram and 6-minute walk distance (6MWD) as part of the observational phase of the study. This sample size achieved > 99% power to detect a 15% difference in TRV in the 2 groups at a significance level of 0.05 using a 2 sided two sample t-test. Other parameters compared between groups included 6MWD, age, blood pressure, body surface area, urine albumin, blood urea nitrogen, ferritin, creatinine, white blood cell count, platelet count, hematocrit, hemoglobin, bilirubin, lactate dehydrogenase, aspartate aminotransferase, absolute reticulocyte count (ARC), absolute neutrophil count and hydroxyurea use. Continuous variables were analyzed with linear regression and 2-sided t-tests and categorical variables were analyzed with Chi-square test. Multivariable linear regression models were constructed using variables significantly associated with TRV in bivariate analyses. Results There were no significant differences in mean± SD TRV (2.62± 0.42 vs 2.62± 0.43, p=0.99) or 6MWD (446± 84 vs 440± 97, p=0.74) between the 2 groups. A history of splenectomy was associated with significantly higher ARC, hemoglobin and hematocrit. When adjusted for hemoglobin and ARC an association of TRV with splenectomy was still not observed (p=0.82). Conclusion Surgical asplenia is not associated with higher TRV compared with presumed auto-infarction of the spleen in a large cohort of adult patients with HbSS. Platelet and WBC counts were also not higher in the splenectomized patients, making it less likely that the thrombotic risk is greater in splenectomized patients compared to the high baseline risk in HbSS patients. The overall greater risk of elevated TRV with asplenia in HbSS cannot be addressed here, because most patients are functionally asplenic even absent surgical resection. However, these results suggest that, distinct from thalassemia, surgical asplenia does seem to not confer additional risk for elevated TRV in HbSS, an important consideration when weighing the risks and benefits of splenectomy. Disclosures: No relevant conflicts of interest to declare.

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Proteinuria is associated with elevated tricuspid regurgitant jet velocity in children with sickle cell disease

Pediatric Blood & Cancer ◽

10.1002/pbc.23338 ◽

2011 ◽

Vol 58 (6) ◽

pp. 937-940 ◽

Cited By ~ 17

Author(s):

Suzanne Forrest ◽

Ashley Kim ◽

Judith Carbonella ◽

Farzana Pashankar

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Jet Velocity ◽

Tricuspid Regurgitant Jet Velocity

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Left ventricular hypertrophy and diastolic dysfunction in children with sickle cell disease are related to asleep and waking oxygen desaturation

Yearbook of Pediatrics ◽

10.1016/j.yped.2011.04.018 ◽

2012 ◽

Vol 2012 ◽

pp. 65-66

Author(s):

J.A. Stockman

Keyword(s):

Sickle Cell Disease ◽

Left Ventricular Hypertrophy ◽

Diastolic Dysfunction ◽

Sickle Cell ◽

Ventricular Hypertrophy ◽

Left Ventricular ◽

Oxygen Desaturation ◽

Cell Disease

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Abstract 65: Anemia-related Heart Failure in Sub-saharan African Sickle Cell Disease Patients

Circulation Research ◽

10.1161/res.121.suppl_1.65 ◽

2017 ◽

Vol 121 (suppl_1) ◽

Author(s):

Adebayo C Atanda ◽

Yahya Aliyu ◽

Oluwafunmilayo Atanda ◽

Aliyu Babadoko ◽

Aisha Suleiman ◽

...

Keyword(s):

Heart Failure ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Systolic Pressure ◽

Left Ventricular ◽

Hemoglobin Level ◽

Sub Saharan Africa ◽

Cell Disease ◽

Jet Velocity ◽

Sub Saharan

Introduction: Anemia has been implicated in heart failure. Existing literatures, involving predominantly African-Americans, suggests that Sickle Cell Disease (SCD) maybe linked to various cardiovascular complications including pulmonary hypertension and left venticular dysfunction. Peculiarly, our study involves exclusively Sub-Saharan population. Method: We conducted a cross sectional observational study of 208 hydroxyurea-naive consecutive SCD patients aged 10-52 years at steady state and 94 healthy non-matched controls who were studied in an out patient clinic in Sub-Saharan Africa. SCD patients were required to have electrophoretic or liquid chromatography documentation of major sickling phenotypes. Control group was required to have non-sickling phenotypes. Cardiac measurements were performed with TransThoracic Echo according to American Society of Echocardiography guidelines. Hemoglobin level was also obtained. Results: Hemoglobin level in SCD group (8.5+/- 1.5) was significant (P<0.001) compared to control (13.8+/- 1.7). Although SCD group had significantly higher values of left ventricular (LV) size, there was no qualitative evidence of LV dysfunction. SCD group had higher values of Ejection Fraction but not statistically significant. There was no evidence of LV wall stiffening to impair proper filling in SCD group, with the ratio of early to late ventricular filling velocities, E/A ratio elevated (1.7+/-0.4 compared to 1.6+/- 0.4; P=0.010). Right ventricular systolic pressure was determined using the formula of 4x Tricuspid Reugurgitant jet (TRV) square as an indirect measurement of Pulmonary arterial systolic pressure. SCD patients had significantly higher mean±SD values for tricuspid regurgitant jet velocity than did the controls (2.1±0.6 vs. 1.8±0.5; p= 0.001). Within the SCD group, there was no clear pattern of worsening diastolic function with increased TRV. Furthermore, E/A had a significant positive relationship with jet velocity in bivariate analysis (R=0.20; P=0.013). Conclusions: We were unable to demonstrate existence of anemia-associated left ventricular dysfunction in Sub-Saharan African with SCD. Further studies is required to highlight the reason behind this finding.

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