Author + information
- Yogesh N.V. Reddy, MD∗ ( and )
- Barry A. Borlaug, MD
- ↵∗Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota 55905
We read with great interest the article by Niss et al. (1) in the March 2016 issue of iJACC. These investigators describe an abnormal mitral inflow pattern, left atrial enlargement, and pulmonary hypertension in a cohort of patients with sickle cell anemia. In the absence of a definitive pathogenesis, they suggest the potential for an underlying restrictive cardiomyopathy as an explanation for the underlying Doppler mitral inflow abnormalities and diastolic dysfunction.
We propose an alternative explanation for the cardiac structural and hemodynamic parameters noted. Sickle cell anemia is characterized by significant anemia, along with compensatory intramedullary and extramedullary hematopoiesis. This may be associated with increased metabolic demand, peripheral vasodilation, and a resultant high–cardiac output state (2). One can also speculate that in addition to anemia, increased metabolic demand and shunting from exuberant bone marrow hematopoiesis may also contribute to a high–cardiac output state. This condition has been reported in other hematologic diseases such as multiple myeloma (3). High-output heart failure may occur if systemic vasodilation decreases relative renal perfusion to the point of causing salt and water retention, elevated filling pressures, and the syndrome of clinical heart failure (4). The increased venous return can lead to an elevated Doppler E/e′ and E/A ratio from an increased volume of blood returning to the left ventricle in early diastole that mimics the mitral inflow pattern seen in restrictive left ventricular filling.
Left atrial volume index, tricuspid regurgitation velocity, and left ventricular diastolic dimension and mass index showed a positive correlation with decreasing hemoglobin and increasing reticulocyte counts. This finding suggests the presence of an underlying high-output heart failure state leading to volume overload, left atrial and ventricular dilation, and eccentric hypertrophy. In addition, the meta-analysis showed that echocardiographically derived stroke volume index and invasive cardiac output were significantly higher than in controls, thus providing further evidence to this theory.
If indeed some patients with sickle cell disease develop true restrictive cardiomyopathy, data on the iron status of these patients would further help elucidate the etiology. Secondary hemochromatosis is common in sickle cell anemia from the repeated blood transfusions patients receive, in addition to increased intestinal iron absorption secondary to ineffective erythropoiesis (5). Iron deposition in the heart secondary to hemochromatosis is a well-described mechanism of restrictive cardiomyopathy and may be a putative pathophysiological mechanism underlying some cases of restrictive cardiomyopathy in sickle cell disease.
Although there may be some patients who develop true restrictive cardiomyopathy, we suspect that a high-output heart failure state potentially underlies many of the hemodynamic and structural changes described in this series of young patients (median age 11 years) with sickle cell disease. It is possible that superimposed insults from secondary hemochromatosis, pulmonary emboli, and recurrent microvascular ischemia may modify the disease manifestation in any individual case. However, it is likely more appropriate to label these patients as having high-output heart failure as opposed to restrictive cardiomyopathy. Data on the echocardiographically derived cardiac index in these patients was not reported, but it will likely help clarify this issue further.
Please note: Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2016 American College of Cardiology Foundation
- Niss O.,
- Quinn C.T.,
- Lane A.,
- et al.
- Castro O.,
- Hoque M.,
- Brown B.D.
- Inanir S.,
- Haznedar R.,
- Atavci S.,
- Unlu M.
- Reddy Y.N.,
- Melenovsky V.,
- Redfield M.M.,
- Nishimura R.A.,
- Borlaug B.A.