Left ventricular-aortic coupling in sickle cell disease underlies diastolic dysfunction

2015 ◽  
Author(s):  
Emilie Bollache ◽  
Nadjia Kachenoura ◽  
Roberto M Lang ◽  
Victor Mor-Avi ◽  
Amit R Patel
Keyword(s):  
Sickle Cell Disease ◽  
Diastolic Dysfunction ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Cell Disease

Risk Factors for Echocardiography-Determined Cardiopulmonary Abnormalities In Sickle Cell Anemia In the Walk-PHaSST Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 260-260 ◽  
Author(s):  
Gregory J. Kato
Keyword(s):  
Sickle Cell Disease ◽  
Diastolic Dysfunction ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fold Increase ◽  
Lateral Wall ◽  
Left Ventricular Diastolic Dysfunction ◽  
Left Ventricular ◽  
Cell Disease ◽  
Ventricular Diastolic Dysfunction

Abstract 260 Background: Elevated right ventricular pressure [1] and left ventricular diastolic dysfunction [2] as assessed by echocardiography are each independently associated with increased mortality in adults with sickle cell anemia. To determine independent risk factors for these echocardiographic findings, we examined a large, prospective, multi-center international cohort in a cross-sectional manner. In a previous study of adults with sickle cell disease, we identified histories of cardiac and renal disease, higher values for serum lactate dehydrogenase (LDH), alkaline phosphatase, and systolic blood pressure, and lower values for transferrin to have independent associations with elevated right ventricular systolic pressure as estimated by echocardiography [1]. Methods: Walk-PHaSST (treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy) includes an on-going observational study of sickle cell disease patients at nine United States Centers and one United Kingdom Center. In the screening phase of the study, clinical evaluation and echocardiography were performed on 720 subjects. For this analysis, we determined among 483 patients with hemoglobin SS baseline clinical associations with the echocardiographic measurements of tricuspid regurgitation velocity (TRV), which reflects right ventricular systolic pressure, and left ventricular lateral wall E/Ea ratio, which reflects left ventricular filling pressure as a measure of diastolic dysfunction. The study prospectively defined moderately elevated TRV as 2.7–2.9 m/sec and markedly elevated TRV as ≥3.0 m/sec. A hemolytic component was derived by principal component analysis from four markers of hemolysis: reticulocyte percent, serum LDH, aspartate aminotransferase and bilirubin. Results: Of 483 hemoglobin SS patients, the median age was 35 years (range of 12 to 69 years) and the gender distribution was 250 females and 233 males. TRV was measured in 453 patients, lateral wall E/Ea was measured in 436 and hemolytic component was calculated in 406. TRV was 2.7–2.9 m/sec in 22% and ≥3.0 m/sec in 17%. By ordinal logistic regression, an increase of age of 10 years was independently associated with a 1.5-fold increase in the odds of progressively higher TRV categories (95% CI of 1.2–1.8; P <0.0005), an increase in the hemolytic component of 2 SD with a 2.4-fold increase in the odds of progressively higher categories (95% CI of 1.5–3.8; P <0.0005), a log increase in the lateral wall E/Ea ratio with a 3.2-fold increase in the odds (95% CI of 1.6–6.6; P=0.001), and a serum creatinine >1.4 mg/dL with a 2.1-fold increase in the odds (95% CI of 1.0–4.3; P=0.047). By linear regression, older age was independently associated with a higher log lateral wall E/Ea ratio (beta=0.005; P <0.0005) as were serum creatinine >1.4 mg/dL (beta=0.23; P <0.0005) and lower hemoglobin concentration (beta=-0.002; P=0.022). Conclusions: The findings of this large prospective, multicenter, international study of patients with sickle cell anemia emphasizes the association of older age, severe hemolytic anemia, renal dysfunction, and left ventricular diastolic dysfunction with high TRV, a previously confirmed marker of early mortality. Clinical trials are indicated to test whether strategies to correct hemolytic anemia and to prevent renal dysfunction in adults and adolescents with sickle cell anemia may prevent or delay the development of left ventricular diastolic dysfunction and/or pulmonary hypertension. References: 1. Gladwin, M.T., et al., Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med, 2004. 350(9): p.886-95. 2. Sachdev, V., et al., Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease. J Am Coll Cardiol, 2007. 49(4): p.472-9. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
2010 ◽  
Vol 116 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Mark C. Johnson ◽  
Fenella J. Kirkham ◽  
Susan Redline ◽  
Carol L. Rosen ◽  
Yan Yan ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Diastolic Dysfunction ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Multivariable Logistic Regression Analysis ◽  
Cell Disease ◽  
Low Oxygen ◽  
Cardiac Abnormalities ◽  
Lv Mass

Abstract Premature death and cardiac abnormalities are described in individuals with sickle cell disease (SCD), but the mechanisms are not well characterized. We tested the hypothesis that cardiac abnormalities in children with SCD are related to sleep-disordered breathing. We enrolled 44 children with SCD (mean age, 10.1 years; range, 4-18 years) in an observational study. Standard and tissue Doppler echocardiography, waking oxygen saturation averaged over 5 minutes, and overnight polysomnography were obtained in participants, each within 7 days. Eccentric left ventricular (LV) hypertrophy was present in 46% of our cohort. After multivariable adjustment, LV mass index was inversely related to average asleep and waking oxygen saturation. For every 1% drop in the average asleep oxygen saturation, there was a 2.1 g/m2.7 increase in LV mass index. LV diastolic dysfunction, as measured by the E/E′ ratio, was present in our subjects and was also associated with low oxygen saturation (sleep or waking). Elevated tricuspid regurgitant velocity (≥ 2.5 m/sec), a measure of pulmonary hypertension, was not predicted by either oxygen saturation or sleep variables with multivariable logistic regression analysis. These data provide evidence that low asleep and waking oxygen saturations are associated with LV abnormalities in children with SCD.

scholarly journals Sickle cell disease: at the crossroads of pulmonary hypertension and diastolic heart failure

Heart ◽  
2019 ◽  
Vol 106 (8) ◽  
pp. 562-568 ◽  
Author(s):  
Katherine C Wood ◽  
Mark T Gladwin ◽  
Adam C Straub
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Sickle Cell ◽  
Diastolic Heart Failure ◽  
Left Ventricular ◽  
Cell Disease ◽  
Lv Diastolic Dysfunction

Sickle cell disease (SCD) is caused by a single point mutation in the gene that codes for beta globin synthesis, causing haemoglobin polymerisation, red blood cell stiffening and haemolysis under low oxygen and pH conditions. Downstream effects include widespread vasculopathy due to recurring vaso-occlusive events and haemolytic anaemia, affecting all organ systems. Cardiopulmonary complications are the leading cause of death in patients with SCD, primarily resulting from diastolic heart failure (HF) and/or pulmonary hypertension (PH). HF in SCD often features biventricular cardiac hypertrophy and left ventricular (LV) diastolic dysfunction. Among HF cases in the general population, approximately half occur with preserved ejection fraction (HFpEF). The insidious evolution of HFpEF differs from the relatively acute evolution of HF with reduced ejection fraction. The PH of SCD has diverse origins, which can be pulmonary arterial (precapillary), pulmonary venous (postcapillary) or pulmonary thromboembolic. It is also appreciated that patients with SCD can develop both precapillary and postcapillary PH, with elevations in LV diastolic pressures, as well as elevations in transpulmonary pressure gradient and pulmonary vascular resistance. Regardless of the cause of PH in SCD, its presence significantly reduces functional capacity and increases mortality. PH that occurs in the presence of HFpEF is usually of postcapillary origin. This review aims to assemble what has been learnt from clinical and animal studies about the manifestation of PH-HFpEF in SCD, specifically the contributions of LV diastolic dysfunction and myocardial fibrosis, in an attempt to gain an understanding of its evolution.

scholarly journals Echocardiographic phenotypes of patients with sickle cell disease. An unsupervised analysis based on etendard cohort

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
T D"humieres ◽  
J Inamo ◽  
S Deswarte ◽  
T Damy ◽  
G Loko ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Cardiac Output ◽  
Sickle Cell Disease ◽  
Diastolic Function ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Integrative Approach ◽  
Cell Disease ◽  
Clinical Profiles ◽  
Cluster 2

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PHRC Backgroung Echocardiography is the cornerstone in the diagnosis of cardiopulmonary involvement in sickle cell disease (SCD). However, given the unique pathophysiology of SCD associating high cardiac output, and various degrees of peripheral vasculopathy, differentiate the pathological from the physiological using echocardiography can be particularly challenging. Purpose This study sought to link cardiac phenotypes in homozygous SCD patients with clinical profiles and outcomes using cluster analysis. Methods We analyzed data of 379 patients with a sufficient echographic dataset included in the French Etendard Cohort, a prospective cohort initially designed to assess the prevalence of pulmonary hypertension. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed. Results Three clusters were identified. Cluster 1 (N = 122) patients had the lowest cardiac output, only mild left cavities remodeling, diastolic dysfunction, and high tricuspid regurgitation velocity (TRV). They were predominantly female, as old as cluster 2, and displayed the most severe functional limitation. Cluster 2 (N = 103) patients had the highest cardiac output, left ventricular mass and a severely dilated left atrium. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (N = 154) patients had mild left cavities remodeling, the best diastolic function and the lowest TRV. They were younger patients with the highest hemoglobin and lowest hemolytic markers. Right heart catheterization was performed in 94 patients. Cluster 1 gathered the majority of precapillary PH while cluster 2 gathered postcapillary PH and no PH was found in cluster 3. After a follow-up of 9.9 years (IQR: 9.3 to 10.5 years) death occurred in 38 patients (10%). Clusters 2 had the worst prognosis with 18% mortality rate vs. 12% in cluster 2 and 5% in cluster 1 (P log-rank = 0,02). Results are summarized in the central illustration. Conclusions Cluster analysis of echocardiographic variables identified 3 phenotypes among SCD patients, each associated with different clinical features and outcome. These findings underlines the necessity to rethink echocardiographic evaluation of SCD patients, with an integrative approach based on simultaneous evaluation of TRV along with left cavities remodeling and diastolic parameters. Abstract Figure.

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

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.

Enalapril Therapy Prevents Cardiac Remodelling of Sickle Cell Disease Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3792-3792
Author(s):  
Sara T. Saad ◽  
Carmen S. Passos Lima ◽  
Osvaldo M. Ueti ◽  
Adriana A. Ueti ◽  
Kleber G. Franchini ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Ace Inhibitors ◽  
Aortic Root ◽  
Fetal Hemoglobin ◽  
Treated Group ◽  
Left Ventricular ◽  
Cell Disease

Abstract Angiotensin-converting enzyme (ACE) inhibitors are capable of decreasing cardiac remodelling in patients with cardiac dysfunction, however their effects on sickle cell disease (SCD) are unknown. Thus, this study aimed to investigate the cardiac effects of enalapril on SCD patients. Thirteen adult patients with sickle cell disease (SCD) and microalbuminuria (3M/10F); 11 sickle cell anemia patients (SCA), 1 Sβ thalassemia patient (Sβ) and 1 patient with hemoglobin SC (SC) were treated with enalapril. Thirteen other SCD patients (4M/9F) without microalbuminuria, matched according to age, diagnosis (11 SCA, 1 Sβ and 1 SC), and levels of hemoglobin, hematocrit and fetal hemoglobin, did not receive enalapril and were followed up as the control group in the same period of study. In the treated group, enalapril (5mg) was administered to 9 SCD patients during the entire study period. One patient did not complete follow-up, and higher doses (7.5mg to 20mg) were administered to 3 patients who developed systolic BP over 120 mmHg during the study period. Median age (28.5 vs 29.0; P= 0.580), baseline values of hemoglobin (8.5 vs 8.4g/dL, P= 0.600), hematocrit (25.0 vs 23.5%, P= 0.500), fetal hemoglobin (4.4 vs 4.1%, P=0.720) and mean blood pressure (MBP; 80 vs 93mmHg, P= 0.13) were similar in treated and untreated patients Echocardiograms were performed before the study entry and once a year in patients and controls. Comparisons of groups were performed at the beginning of the study and after 36 months of follow-up using the Wilcoxon-signed rank test and Spearman coefficient. At 36 months of follow-up, MBP was lower than the baseline value (93 mmHg vs 87 mmHg, P= 0.018) in the treated group. Significant increases in left ventricular mass (192 vs 231g, P= 0.005), posterior left ventricular wall thickness in end-diastole (8.5 vs 10.0mm, P= 0.013), left ventricular mass index (114.4 vs 131g/m2, P= 0.043), interventricular septal wall thickness in end-diastole (9.0 vs 9.5mm, P= 0.036) and aortic root dimension (28 vs 32mm, P= 0.009) values were seen in untreated, but not in enalapril treated patients. No major changes were seen in left ventricular ejection fraction, left ventricular systolic diameter, left ventricular diastolic dimension and left atrial diameter, in both groups, along the observational period. No significant correlation was detected between the data here presented. At the end of the study, no symptoms or signals related to cardiac failure were found in any of the enrolled patients. These results indicate a trend toward cardiac and aortic root remodeling in untreated SCD patients and suggest that long-term treatment with ACE inhibitors has beneficial effects on the cardiac remodeling of SCD patients and could be indicated for adult patients, if an increase in baseline blood pressure occurs.

Plasma Level of NT-Pro-BNP In Children with Sickle Cell Disease Is Associated with Degree of Anemia and Left Ventricular Measures: The PUSH Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 948-948 ◽  
Author(s):  
Gregory J. Kato ◽  
Craig Sable ◽  
Gregory Ensing ◽  
Niti Dham ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Regression Model ◽  
Sickle Cell ◽  
Logistic Regression Model ◽  
Clinical Laboratory ◽  
Left Ventricular ◽  
Filling Pressure ◽  
Cell Disease

Abstract Abstract 948 Background: Amino-terminal pro-brain type natriuretic peptide (NT-proBNP) is a widely used clinical laboratory marker of left ventricular stress, although it is also known to be elevated in adults with right ventricular stress due to pulmonary hypertension associated with sickle cell disease (SCD) and other disorders. NT-proBNP is associated with early mortality in adults with SCD. Methods: Using a standard clinical laboratory assay, we measured NT-proBNP in 346 children (median age 12; IQR 7–16 years) with SCD enrolled in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study, an ongoing, longitudinal and observational multicenter study of children with sickle cell disease. In order to adjust for age, a known confounding factor of NT-proBNP in young children, we compared the characteristics of children with the top quartile of NT-proBNP for each 3-year increment of age with those of children in the remaining three quartiles for that age increment. We examined several factors alone and as part of a logistic regression model. Results: In univariate analyses, high expression of NT-proBNP was associated with lower hemoglobin levels (median 83 vs. 87 gm/L, p=0.0006). The high NT-proBNP group also had a higher hemolytic component, a principal component-derived index of the common properties of the hemolytic markers reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and bilirubin (median 0.5 vs. 0.7 relative units, p=0.021). The high NT-proBNP group had a higher prevalence of high left ventricular filling pressure, as indicated by the mitral inflow E wave to tissue Doppler E wave (E/Etdi) above 9.22 (13.1% vs. 2.9%, p<0.001) and left ventricular dilatation (median internal diastolic diameter z-score 2.1 vs. 1.5, p=0.013). There was a trend toward higher prevalence of elevated estimated pulmonary artery pressures as indicated by tricuspid regurgitant velocity of 2.6 m/s or higher (17.1% vs. 10.8%, p=0.14), and higher ferritin (median 339 vs. 199, p=0.15). Children on hydroxyurea treatment had lower median NTproBNP levels (77 vs. 121 pg/mL, p=0.005). In a logistic regression model, hemoglobin (odds ratio 0.7, 95% confidence interval 0.6–0.9, p=0.001) and E/ETdi>9.22 were independently associated with high NT-proBNP levels. Conclusions: After adjustment for age in children with SCD, upper quartile NTproBNP is independently associated with severity of anemia and echocardiographic markers of left ventricular size and diastolic filling pressure. At this age, they have not yet developed the association observed prominently in SCD adults between NT-proBNP and elevated pulmonary arterial pressures. Our data lends support to childhood being considered as a pre-symptomatic phase of pulmonary hypertension; which could be targeted for clinical trials of preventative strategies to prevent adult onset of pulmonary vascular changes associated with higher NT-proBNP and higher TRV. Hydroxyurea therapy is associated in our results from children with SCD with lower NT-proBNP, making it an attractive candidate for a trial in children with SCD to prevent pulmonary hypertension in adulthood. NT-proBNP in childhood SCD remains a marker of left ventricular measures, identifying this additional feature of cardiopulmonary risk. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document