Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia

Omar Niss, Robert Fleck, Fowe Makue, Tarek Alsaied, Payal Desai, Jeffrey Towbin, Punam Malik, Michael D. Taylor, Charles T. Quinn

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age, 23 6 13 years) and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1 measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared with controls (0.44 6 0.08 vs 0.26 6 0.02, P < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71%) had diastolic abnormalities, and 7 patients (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 6 0.07 vs 0.37 6 0.04, P 5 .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 6 261 vs 33 6 33 pg/mL, P 5 .04) but lower hemoglobin (8.4 6 0.3 vs 10.9 6 1.4 g/dL, P 5 .004) compared with participants with normal diastolic function. Participants with the highest ECV values (‡0.40) were more likely to have diastolic dysfunction (P 5 .003) and increased left atrial volume (57 6 11 vs 46 6 12 mL/m2, P 5 .04) compared with those with ECV <0.4. ECV correlated with hemoglobin (r 5 20.46, P 5 .03) and NT-proBNP (r 5 0.62, P 5 .001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.

Original languageEnglish (US)
Pages (from-to)205-213
Number of pages9
JournalBlood
Volume130
Issue number2
DOIs
StatePublished - Jul 13 2017

Fingerprint

Sickle Cell Anemia
Volume fraction
Fibrosis
Gadolinium
Hemoglobins
Magnetic resonance measurement
Echocardiography
Brain Natriuretic Peptide
Cardiomyopathies
Anemia
Myocardium
Magnetic Resonance Spectroscopy
Blood
Mortality
pro-brain natriuretic peptide (1-76)

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. / Niss, Omar; Fleck, Robert; Makue, Fowe; Alsaied, Tarek; Desai, Payal; Towbin, Jeffrey; Malik, Punam; Taylor, Michael D.; Quinn, Charles T.

In: Blood, Vol. 130, No. 2, 13.07.2017, p. 205-213.

Research output: Contribution to journalArticle

Niss, O, Fleck, R, Makue, F, Alsaied, T, Desai, P, Towbin, J, Malik, P, Taylor, MD & Quinn, CT 2017, 'Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia', Blood, vol. 130, no. 2, pp. 205-213. https://doi.org/10.1182/blood-2017-02-767624
Niss, Omar ; Fleck, Robert ; Makue, Fowe ; Alsaied, Tarek ; Desai, Payal ; Towbin, Jeffrey ; Malik, Punam ; Taylor, Michael D. ; Quinn, Charles T. / Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. In: Blood. 2017 ; Vol. 130, No. 2. pp. 205-213.
@article{8f6f8089b14c4aa3adda671bd03c7443,
title = "Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia",
abstract = "Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age, 23 6 13 years) and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1 measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared with controls (0.44 6 0.08 vs 0.26 6 0.02, P < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71{\%}) had diastolic abnormalities, and 7 patients (29{\%}) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 6 0.07 vs 0.37 6 0.04, P 5 .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 6 261 vs 33 6 33 pg/mL, P 5 .04) but lower hemoglobin (8.4 6 0.3 vs 10.9 6 1.4 g/dL, P 5 .004) compared with participants with normal diastolic function. Participants with the highest ECV values (‡0.40) were more likely to have diastolic dysfunction (P 5 .003) and increased left atrial volume (57 6 11 vs 46 6 12 mL/m2, P 5 .04) compared with those with ECV <0.4. ECV correlated with hemoglobin (r 5 20.46, P 5 .03) and NT-proBNP (r 5 0.62, P 5 .001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.",
author = "Omar Niss and Robert Fleck and Fowe Makue and Tarek Alsaied and Payal Desai and Jeffrey Towbin and Punam Malik and Taylor, {Michael D.} and Quinn, {Charles T.}",
year = "2017",
month = "7",
day = "13",
doi = "10.1182/blood-2017-02-767624",
language = "English (US)",
volume = "130",
pages = "205--213",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

TY - JOUR

T1 - Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia

AU - Niss, Omar

AU - Fleck, Robert

AU - Makue, Fowe

AU - Alsaied, Tarek

AU - Desai, Payal

AU - Towbin, Jeffrey

AU - Malik, Punam

AU - Taylor, Michael D.

AU - Quinn, Charles T.

PY - 2017/7/13

Y1 - 2017/7/13

N2 - Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age, 23 6 13 years) and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1 measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared with controls (0.44 6 0.08 vs 0.26 6 0.02, P < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71%) had diastolic abnormalities, and 7 patients (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 6 0.07 vs 0.37 6 0.04, P 5 .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 6 261 vs 33 6 33 pg/mL, P 5 .04) but lower hemoglobin (8.4 6 0.3 vs 10.9 6 1.4 g/dL, P 5 .004) compared with participants with normal diastolic function. Participants with the highest ECV values (‡0.40) were more likely to have diastolic dysfunction (P 5 .003) and increased left atrial volume (57 6 11 vs 46 6 12 mL/m2, P 5 .04) compared with those with ECV <0.4. ECV correlated with hemoglobin (r 5 20.46, P 5 .03) and NT-proBNP (r 5 0.62, P 5 .001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.

AB - Sickle cell anemia (SCA)-related cardiomyopathy is characterized by diastolic dysfunction and hyperdynamic features. Diastolic dysfunction portends early mortality in SCA. Diastolic dysfunction is associated with microscopic myocardial fibrosis in SCA mice, but the cause of diastolic dysfunction in humans with SCA is unknown. We used cardiac magnetic resonance measurements of extracellular volume fraction (ECV) to discover and quantify diffuse myocardial fibrosis in 25 individuals with SCA (mean age, 23 6 13 years) and determine the association between diffuse myocardial fibrosis and diastolic dysfunction. ECV was calculated from pre- and post-gadolinium T1 measurements of blood and myocardium, and diastolic function was assessed by echocardiography. ECV was markedly increased in all participants compared with controls (0.44 6 0.08 vs 0.26 6 0.02, P < .0001), indicating the presence of diffuse myocardial fibrosis. Seventeen patients (71%) had diastolic abnormalities, and 7 patients (29%) met the definition of diastolic dysfunction. Participants with diastolic dysfunction had higher ECV (0.49 6 0.07 vs 0.37 6 0.04, P 5 .01) and N-terminal pro-brain natriuretic peptide (NT-proBNP; 191 6 261 vs 33 6 33 pg/mL, P 5 .04) but lower hemoglobin (8.4 6 0.3 vs 10.9 6 1.4 g/dL, P 5 .004) compared with participants with normal diastolic function. Participants with the highest ECV values (‡0.40) were more likely to have diastolic dysfunction (P 5 .003) and increased left atrial volume (57 6 11 vs 46 6 12 mL/m2, P 5 .04) compared with those with ECV <0.4. ECV correlated with hemoglobin (r 5 20.46, P 5 .03) and NT-proBNP (r 5 0.62, P 5 .001). In conclusion, diffuse myocardial fibrosis, determined by ECV, is a common and previously underappreciated feature of SCA that is associated with diastolic dysfunction, anemia, and high NT-proBNP. Diffuse myocardial fibrosis is a novel mechanism that appears to underlie diastolic dysfunction in SCA.

UR - http://www.scopus.com/inward/record.url?scp=85023780213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023780213&partnerID=8YFLogxK

U2 - 10.1182/blood-2017-02-767624

DO - 10.1182/blood-2017-02-767624

M3 - Article

C2 - 28507082

AN - SCOPUS:85023780213

VL - 130

SP - 205

EP - 213

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -