Clinical Assessment of the Risk for Sudden Cardiac Death in Patients with Sickle Cell Anemia

Fontaine, John M.; Ofili, Elizabeth; Adenaike, Michael B.; VanDecker, William; Haywood, L. Julian

doi:10.1016/s0027-9684(15)31268-2

Cited by 8 publications

(9 citation statements)

References 25 publications

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“…According to the study of Darbari et al (), who analysed clinical and/or autopsy findings at the time of death among adults with SCD, 23·4% of the deaths overall were sudden and occurred either at home or in hospital. PH, cardiac arrhythmias, autonomic nervous system abnormalities, LV hypertrophy, and poor LV systolic function seem to contribute to sudden death in some patients (James et al , ; Romero Mestre et al , ; Fontaine et al , ). Proposed prognostic models for risk stratification of SCD patients include echocardiographic detection of LV hypertrophy and abnormal microvolt T‐wave alternans (TWA) test (Fontaine et al , ).…”

Section: Myocardial Ischaemia (Mi) Cardiac‐related Chest Pain and Sumentioning

confidence: 99%

Sickle‐cell disease and the heart: review of the current literature

2012

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Summary Sickle cell disease (SCD) is an inherited chronic haemolytic anaemia whose clinical manifestations arise from the tendency of the haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape due to a single nucleotide change in the β‐globin. Vascular occlusion of small and large vessels can lead to chronic damage of multiple organs including brain, lung, bone, kidney, liver, spleen, and retina. However, the extent to which SCD impacts myocardial function is not very clear. Cardiovascular manifestations include both right and left ventricular systolic and diastolic dysfunction, elevated cardiac output, cardiomegaly and myocardial ischaemia. Progressive heart damage from iron overload occurs in patients requiring routine transfusion therapy. Pulmonary hypertension resulting from intravascular haemolysis has also been recognized as a major complication that independently correlates with survival. This review summarizes all available data for the heart complications in SCD to update the physicians for their appearance, diagnostic procedures and possible management.

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Section: Myocardial Ischaemia (Mi) Cardiac‐related Chest Pain and Sumentioning

confidence: 99%

Sickle‐cell disease and the heart: review of the current literature

2012

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“…Despite improved early survival, nearly one-third of young adults with SCA die suddenly (3)(4)(5)(6)(7)(8)(9). The sickle myocardium has been presumed to be relatively resistant to the effects of sickling (10), and studies/autopsies show little evidence of atherosclerosis or coronary disease (11)(12)(13)(14).…”

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confidence: 99%

Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

Bakeer

James

Roy

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA.sickle cell anemia | cardiomyopathy | restrictive physiology | arrhythmias | sudden death S ickle cell anemia (SCA) results from a point mutation in the β-globin gene and affects millions world-wide. It is characterized by production of the mutant hemoglobin S (HbS), which polymerizes upon deoxygenation and distorts the shape of RBCs, increasing their propensity to hemolysis and microvascular occlusion. Recurrent cycles of HbS polymerization result in a host of acute and chronic complications, including vaso-occlusive pain crisis, chronic hemolytic anemia, and organ damage. SCA-associated mortality rates have improved because of early diagnosis with universal newborn screening, immunization, and penicillin prophylaxis, which has changed the natural history of SCA (1, 2) and the impact of SCA on organ pathologies is now becoming evident.Despite improved early survival, nearly one-third of young adults with SCA die suddenly (3-9). The sickle myocardium has been presumed to be relatively resistant to the effects of sickling (10), and studies/autopsies show little evidence of atherosclerosis or coronary disease (11)(12)(13)(14). Mildly increased systolic pulmonary arterial pressure (PAP) estimated by tricuspid regurgitant jet vel...

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“…Although observational studies of the prevalence of ECG abnormalities in persons with SCD have been done, they reveal abnormalities that are of unknown clinical significance. Studies found that the prevalence of cardiac enlargement ranged between 22 percent and 76 percent, 64,65 and ventricular hypertrophy prevalence was found to be between 28 percent and 37 percent, 66,67 The presence of nonspecific S-T abnormalities was found to be between 18.5 percent and 52 percent. 68 First-degree atrioventricular block was found in 8 percent of people in one study, 67 and intraventricular conduction delay was found in 4 percent of people in another study.…”

Section: Introductionmentioning

confidence: 98%

“…68 First-degree atrioventricular block was found in 8 percent of people in one study, 67 and intraventricular conduction delay was found in 4 percent of people in another study. 66 Prolonged QTc ranged between 15 percent and 50 percent prevalence. Overall, there was no significant difference in the prevalence of prolonged QTc between people with and without SCD, and the presence of prolonged QTc did not significantly affect mortality.…”

Section: Introductionmentioning

confidence: 99%