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Cited by 147Hemoglobinopathies and Related DisordersPulmonary Hypertension Research and TreatmentsCardiovascular Function and Risk Factors

Echocardiographic Markers of Elevated Pulmonary Pressure and Left Ventricular Diastolic Dysfunction Are Associated With Exercise Intolerance in Adults and Adolescents With Homozygous Sickle Cell Anemia in the United States and United Kingdom

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Sachdev, Vandana, Kato, Gregory J., Gibbs, J. Simon R., Barst, Robyn J., Machado, Roberto F., Nouraie, Mehdi, Hassell, Kathryn L., Little, Jane A. +14 more·2011·Circulation
DOI 10.1161/circulationaha.111.032920PMC PMC3183314
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Abstract

Background—: Noninvasively assessed pulmonary pressure elevations and left ventricular (LV) diastolic dysfunction are associated with increased mortality in adults with sickle cell disease, but their relationship to exercise intolerance has not been evaluated prospectively. Methods and Results—: Echocardiography, 6-minute walk distance, hemolytic rate, and serum concentrations of ferritin and erythropoietin were evaluated in a cohort of 483 subjects with homozygous hemoglobin S in the US and UK Walk–Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid regurgitation velocity, which reflects systolic pulmonary artery pressure, was 2.7 to <3.0 m/s (mean±SD, 2.8±0.1) in 26% of the subjects and ≥3.0 m/s (mean±SD, 3.4±0.4) in 11%. The LV lateral E/e′ ratio, which has been shown to reflect LV filling pressure in other conditions but has not been studied in sickle cell disease, was significantly higher in the groups with tricuspid regurgitation velocity ≥2.7 m/s. Increased hemolysis ( P <0.0001), LV lateral E/e′ ratio ( P =0.0001), blood urea nitrogen ( P =0.0002), and erythropoietin ( P =0.002) were independently associated with an increased tricuspid regurgitation velocity. Furthermore, female sex ( P <0.0001), older age ( P <0.0001), LV lateral E/e′ ratio ( P =0.014), and tricuspid regurgitation velocity ( P =0.019) were independent predictors of a shorter 6-minute walk distance. Conclusions—: Echocardiography-estimated elevated pulmonary artery systolic pressure and LV lateral E/e′ ratio were independently associated with poor exercise capacity in a large cohort of patients with sickle cell anemia. Controlled trials investigating whether strategies to prevent or delay pulmonary hypertension and/or LV diastolic dysfunction will improve exercise capacity and long-term outcomes in sickle cell anemia should be considered. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00492531.

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  • Mild increases of tricuspid regurgitant jet velocity >2.5-2.7 m/s are associated with increased risk of death.

    “even mild increases of >2.5–2.7 m/s are associated with increased risk of death (58, 77, 110, 188–190).”

    From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [77]

    The Discussion (page unavailable) states that increased tricuspid regurgitant velocity is a marker of increased mortality in adults with sickle cell disease. The Methods and Results use a 2.7 m/s cutoff, but the paper does not link the specific >2.5–2.7 m/s range to mortality; its own outcome analysis concerns six-minute walk distance. (LLM, conf=0.85)

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  • Development of pulmonary hypertension is related to pulmonary vascular disease in the setting of intravascular hemolysis and thrombotic events, but can also occur secondary to diastolic left heart disease.

    “While the development of pulmonary hypertension is related to pulmonary vascular disease in the setting of intravascular hemolysis and thrombotic events, it can also occur secondary to diastolic left heart disease (77, 82).”

    From Pathophysiology of Sickle Cell Disease (2019) · cites this paper as [77]

    The Discussion (page unavailable) reports that confirmed pulmonary hypertension can reflect either increased pulmonary vascular resistance or pulmonary venous hypertension attributed to left ventricular diastolic dysfunction. It also links hemolytic severity to elevated estimated pulmonary pressure. The paper does not link thrombotic events to the development of pulmonary hypertension, so that part of the claim is unsupported. (LLM, conf=0.86)

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Authors
Sachdev, V., Kato, G. J., Gibbs, J. S. R., Barst, R. J., Machado, R. F., Nouraie, M., Hassell, K. L., Little, J. A., Schraufnagel, D. E., Krishnamurti, L., Novelli, E. M., Girgis, R. E., Morris, C. R., Rosenzweig, E. B., Badesch, D. B., Lanzkron, S., Castro, O. L., Taylor, J. G., Hannoush, H., Goldsmith, J. C., Gladwin, M. T., & Gordeuk, V. R.
Affiliations
Howard University (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2011-09-27
Volume
124
Issue
13
Pages
1452-1460
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.111.032920
PMC
PMC3183314
OpenAlex
W2165932923
Cited by
147
References
53
Citations by year
2026: 8 · 2025: 8 · 2024: 4 · 2023: 10 · 2022: 10 · 2021: 15 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 9 · 2016: 11 · 2015: 12 · 2014: 10 · 2013: 8 · 2012: 12
FWCI
5.01
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 HL999999, 5r01hl079912-04)
  • U.S. Public Health Service (HHSN268200617182C)
  • National Heart, Lung, and Blood Institute (R01-HL079912, 1 R01 HL079912-02, R01HL096973, U54HL090508, ZIAHL005116, U10HL083748, R25HL003679, R01HL098032, K23HL083089)
  • National Institute of Diabetes and Digestive and Kidney Diseases (RC1DK085852, DK085852)
  • National Center for Research Resources (UL1RR024131, 2M0I RR10284-10, M01RR010284)
Topics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords
sickle cell disease, pulmonary hypertension, left ventricular diastolic dysfunction, exercise intolerance, tricuspid regurgitation velocity, E/e' ratio, 6-minute walk distance, hemolysis, erythropoietin, ferritin, blood urea nitrogen, echocardiographic markers, adolescents, adults, sex differences
MeSH terms
Adolescent, Adult, Aged, Anemia, Sickle Cell, Child, Echocardiography, Exercise Test, Female, United Kingdom, Homozygote, Humans, Hypertension, Pulmonary, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, Pulmonary Artery, Tricuspid Valve Insufficiency, United States, Multivariate Analysis, Exercise Tolerance, Ventricular Dysfunction, Left, Young Adult, Familial Primary Pulmonary Hypertension

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