Cardiomyopathy in Sickle Cell Disease

Abstract

Sickle cell disease (SCD) is an inherited disorder that occurs due to point mutation in the betaglobin chain resulting in the production of hemoglobin S that tends to become rigid and sickleshaped under low oxygen concentration. These sickle-shaped red blood cells (RBCs) obstruct the blood vessels leading to reduced blood flow to the organs, causing ischemia and tissue fibrosis. These sickle RBCs being abnormal in shape are frequently sequestered by the spleen, creating a state of chronic anemia in the body. This chronic anemia leads to a high cardiac output state causing cardiac remodeling. To tackle chronic anemia, patients are frequently treated with blood transfusions that makes them more prone to the risk of iron overload (from newly transfused RBCs and iron release from the RBCs that just got sequestered as well as from volume overload) and volume overload causing left ventricular (LV) dilation. The abovementioned mechanism of cardiac hypertrophy, along with LV dilation together, makes SCDrelated cardiomyopathy unique cardiomyopathy with features of restrictive cardiomyopathy with LV dilation. It is interesting to note here that even though there is a presence of LV dilatation, Systolic dysfunction is very uncommon in SCD-related cardiomyopathy.

Exercise‐induced changes of vital signs in adults with sickle cell disease

“…This concept was supported by our finding that the other component of cardiac output, heart rate, was not a predictor of mortality. It is possible that inability to increase systolic blood pressure during exercise that we observed is related to the development of heart failure with preserved ejection fraction (HFpEF), or right heart dysfunction in the setting of high pulmonary pressures, or a combination of both pathologies 33,34 . Decreased risk of mortality associated with exercise‐induced increases of systolic blood pressure has also been identified in other conditions.…”

Cardiac Chamber Quantification by Echocardiography in Adults With Sickle Cell Disease: Need Attention to Eccentric Hypertrophy

“…In our study, serum ferritin level is an independent risk factor for cardiac hypertrophy, and effective chelation therapy may benefit these patients. However, several studies have shown that myocardial iron overload is not common in patients with SCA [ 6 ]. Therefore, other non-ferrous mechanisms are more responsible for the cardiac geometry changes seen in these patients.…”

“…With the renin-angiotensin-aldosterone system (RAAS) activation due to chronic anemia and peripheral vascular dilatation, cardiac remodeling is triggered, and dilatation begins to occur in the left ventricle. This dilatation further triggers compensatory eccentric cardiac hypertrophy [ 6 ]. Conditions such as increased iron load (due to chronic blood transfusion) and pulmonary hypertension associated with decreased nitric oxide also contribute to ventricular hypertrophy.…”

Recent Progress in Drug Repurposing Using Protein Variants and Amino Acids in Disease Phenotypes/Disorders

“…Within these are hemoglobinopathy including sickle cell disease (SCD), which are caused by a single germ-line mutation substituting (A to T) in the codon for amino acid 6. The change converts a glutamic acid codon (GAG) to a valine codon (GTG) [29,30].…”

“…Further, this mutation is thought in part to be responsible for 40-50% of hereditary cases of ALS, and 5-10% of cases without family history. This mutation consists of an expansion of a sequence of hexanucleotide (GGGGCC) DNA bases, going from a few copies (less than 20 in a healthy person) to more than 1000 copies [30]. Until now, it still remains unclear how this GGGGCC base repeat expansions cause neurodegeneration in ALS.…”