Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.

TitleMechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.
Publication TypeJournal Article
Year of Publication2014
AuthorsDesai AA, Patel AR, Ahmad H, Groth JV, Thiruvoipati T, Turner K, Yodwut C, Czobor P, Artz N, Machado RF, Garcia JGN, Lang RM
JournalCirc Cardiovasc Imaging
Date Published2014 May
ISSN Number1942-0080
KeywordsAdult, Anemia, Sickle Cell, Cardiomyopathies, Cohort Studies, Contrast Media, Echocardiography, Female, Gadolinium DTPA, Humans, Image Enhancement, Image Processing, Computer-Assisted, Male

<p><b>BACKGROUND: </b>Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms.</p><p><b>METHODS AND RESULTS: </b>Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all).</p><p><b>CONCLUSIONS: </b>Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular diastolic dysfunction is predominantly correlated with increased aortic stiffness.</p><p><b>CLINICAL TRIAL REGISTRATION URL: </b> Unique identifier: NCT01044901.</p>

Alternate JournalCirc Cardiovasc Imaging
PubMed ID24676783
PubMed Central IDPMC4326424
Grant ListUL1 TR000430 / TR / NCATS NIH HHS / United States
R01 HL111656 / HL / NHLBI NIH HHS / United States
K23 HL098454 / HL / NHLBI NIH HHS / United States
F32 HL090359 / HL / NHLBI NIH HHS / United States
UL1RR029879 / RR / NCRR NIH HHS / United States
F32HL090359 / HL / NHLBI NIH HHS / United States
L30 TR001244 / TR / NCATS NIH HHS / United States
K23HL098454 / HL / NHLBI NIH HHS / United States
L30 HL115611 / HL / NHLBI NIH HHS / United States
UL1 RR029879 / RR / NCRR NIH HHS / United States