Diastolic Dysfunction Is an Independent Risk Factor for Death in Patients With Sickle Cell Disease

Sachdev, Vandana; Machado, Roberto F.; Shizukuda, Yukitaka; Rao, Yesoda N.; Sidenko, Stanislav; Ernst, Inez; Peter, Marilyn St.; Coles, Wynona; Rosing, Douglas R.; Blackwelder, William C.; Castro, Oswaldo; Kato, Gregory J.; Gladwin, Mark T.

doi:10.1016/j.jacc.2006.09.038

Cited by 261 publications

(252 citation statements)

References 43 publications

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“…In a formerly studied group of S-Thal patients, Tei index, which is considered to express both systolic and diastolic LV function, was found to be impaired [5]. In SCD, diastolic dysfunction has recently been noticed in 18% of cases in a large cohort, being at the same time an independent predictor of mortality [19]. Systolic and diastolic LV dysfunctions in the present study were found to be age-related.…”

Section: Discussionsupporting

confidence: 47%

“…In the individual patient analysis (Table 3), on the other hand, three patients (2.6%), all with normal coronary arteries and without history of hypertension, had evident LV systolic dysfunction (ejection fraction <55%). In a recent study referred on LV function in SCD, an even higher occurrence (9%) of ejection fraction impairment was noticed [19].…”

Section: Discussionmentioning

confidence: 91%

“…Additional factors in sickling syndromes such as thromboembolism, repeated episodes of respiratory track infections, acute chest syndrome, and LV dysfunction may also play a role in lung injury affecting the continuous gradual increase of pulmonary vascular resistance. Moreover, diastolic LV dysfunction was shown to be an independent factor for PHT development in SCD [19]. The recent observation that PHT is a common finding in various forms of chronic hemolytic anemias, both hereditary and acquired ones [37], raised the concept that PHT should somehow be related to hemolysis.…”

Section: Discussionmentioning

confidence: 99%

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Cardiac involvement in sickle β-thalassemia

et al. 2008

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Cardiovascular involvement is a leading cause of mortality and morbidity in patients with inherited hemoglobinopathies, but it has not been adequately assessed in sickle β-thalassemia. We evaluated 115 sickle β-thalassemia patients, aged 34±14 years, along with 50 healthy controls, by resting echocardiography. Patients with systolic left ventricular (LV) dysfunction or severe pulmonary hypertension (PHT) also underwent left and right cardiac catheterization and cardiac magnetic resonance imaging (CMR). Left and right chamber dimensions, LV mass, and cardiac index were significantly higher in patients compared to controls (p<0.001 in most cases). Three patients (2.9%) had reduced LV ejection fraction (<55%); mean LV ejection fraction was significantly lower in patients (p< 0.001). Left and right ventricular systolic tissue Doppler indices and LV diastolic tissue Doppler indices were also impaired in patients. All three patients with systolic LV dysfunction had normal coronary arteries and mild myocardial iron load (CMR T2* values, 18-25 ms). Systolic pulmonary artery pressure was significantly higher in patients compared to controls (p=0.002); PHT was present in 28 patients (27%), while severe PHT in three (2.9%). In three patients with severe PHT, only one had impaired LV ejection fraction and increased pulmonary wedge pressure. Overall, three patients (2.9%) had a history of heart failure, two with systolic LV dysfunction, and one with severe PHT. Cardiac involvement in sickle β-thalassemia concerns biventricular dilatation and dysfunction along with PHT, leading to congestive heart failure.

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Section: Discussionsupporting

confidence: 47%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Cardiac involvement in sickle β-thalassemia

et al. 2008

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“…Excess production of reactive oxygen species (ROS) has been implicated in progression of chronic heart failure as well as in other cardiovascular disorders including ischemia-reperfusion injury and cardiovascular complications of hemolytic diseases [2][3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Hemopexin counteracts systolic dysfunction induced by heme-driven oxidative stress

Ingoglia

Sag

Rex

et al. 2017

Free Radical Biology and Medicine

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Heart failure is a leading cause of morbidity and mortality in patients affected by different disorders associated to intravascular hemolysis. The leading factor is the presence of pathologic amount of pro-oxidant free heme in the bloodstream, due to the exhaustion of the natural heme scavenger Hemopexin (Hx). Here, we evaluated whether free heme directly affects cardiac function, and tested the therapeutic potential of replenishing serum Hx for increasing serum heme buffering capacity.The effect of heme on cardiac function was assessed in vitro, on primary cardiomyocytes and H9c2 myoblast cell line, and in vivo, in Hx -/-mice and in genetic and acquired mouse models of intravascular hemolysis. Purified Hx or anti-oxidants N-Acetyl-L-cysteine and α-tocopherol were used to counteract heme cardiotoxicity.In mice, Hx loss/depletion resulted in heme accumulation and enhanced reactive oxygen species (ROS) production in the heart, which ultimately led to severe systolic dysfunction. Similarly, high ROS reduced systolic Ca 2+ transient amplitudes and fractional shortening in primary cardiomyocytes exposed to free heme. In keeping with these Ca 2+ handling alterations, oxidation and CaMKIIdependent phosphorylation of Ryanodine Receptor 2 were higher in Hx -/-hearts than in controls.Administration of anti-oxidants prevented systolic failure both in vitro and in vivo. Intriguingly, Hx rescued contraction defects of heme-treated cardiomyocytes and preserved cardiac function in hemolytic mice.We show that heme-mediated oxidative stress perturbs cardiac Ca 2+ homeostasis and promotes contractile dysfunction. Scavenging heme, Hx counteracts cardiac heme toxicity and preserves left ventricular function. Our data generate the rationale to consider the therapeutic use of Hx to limit the cardiotoxicity of free heme in hemolytic disorders.

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“…Diastolic dysfunction has been associated with increased age, hypertension, and renal failure and has been identified as an independent risk factors for mortality in patients with SCD 3,4 .…”

Section: Sickle Cell Diseasementioning

confidence: 99%