ATLANTA — Vitamin D deficiency was strongly associated with high cardiac iron and increased ventricular dysfunction in a retrospective review of 24 young thal-assemia major patients.
A review of their medical records showed levels of vitamin D(25[OH]D), the predominant circulating form of vitamin D, were “markedly depressed” in 13 patients and borderline depressed in the remaining patients, said Dr. John C. Wood of Children's Hospital Los Angeles and Keck School of Medicine at the University of Southern California, Los Angeles. There were 11 girls and 13 boys; mean age was 15 years.
Vitamin D(25[OH]D) levels less than 20 ng/mL are considered deficient and D(25[OH]D) levels 20–30 ng/mL are borderline or insufficient, Dr. Wood said in a presentation at the annual meeting of the American Society of Hematology. In this study, the mean D(25[OH]D) was 17 ng/mL.
The vitamin D levels were then compared with cardiac R2*–a surrogate MRI measure of the amount of iron in the heart—and left ventricular ejection fraction (LVEF) from each patient's most recent cardiac MRI. As vitamin D levels decreased, cardiac R2* increased. Vitamin D(25[OH]D) levels below 13 ng/mL were associated with severe cardiac iron loading. LVEF also decreased as D25-OH decreased.
“In our MRI laboratory, an ejection fraction less than 56% is considered abnormal and indicates poor pump function. In these patients, there was a proportional association between vitamin D(25[OH]D) levels and cardiac function. The four patients with the lowest D(25[OH]D) had an LVEF between 50% and 54%,” he said.
The population also was moderately iron overloaded, with mean ferritin levels of 2,089 ng/mL, liver iron 14 mg/g dry weight, transferrin saturation 84%, and cardiac R2* 65 Hz. The normal R2* should not exceed 50 Hz. “Vitamin D deficiency … is extremely common in thalassemia. Twenty-three of the 24 patients in our study had levels that are considered inadequate to ensure optimal calcium absorption and bone mineralization,” he said in an interview. Low vitamin D is linked to decreased cardiac function, muscle weakness, glucose insensitivity, and refractory congestive heart failure.
Increased iron in the heart becomes evident in children with thalassemia major around the age of 9 years. Two-thirds of adults with thalassemia have cardiac iron deposition. Iron cardiomyopathy is the leading cause of death in thalassemia. “Our study describes an association between low vitamin D, high cardiac iron, and increased ventricular dysfunction. We cannot prove [cause and effect], but vitamin D might be worsening the cardiac iron overload and the cardiac dysfunction through its modulation of calcium signaling in these patients.”
“Vitamin D deficiency is extremely common in thalassemia, and since osteoporosis is ubiquitous in this disease, vitamin D screening and replacement are probably indicated regardless of the heart findings,” Dr. Wood said.
He added that low vitamin D produces secondary hyperparathyroidism, which exacerbates heart failure of any etiology. Because of this, thalassemia patients with ventricular dysfunction should have their vitamin D levels assessed, and replacement should be started if these levels are low.
The National Heart, Lung, and Blood Institute, the Centers for Disease Control and Prevention, and Novartis Pharma funded the study. Dr. Wood disclosed he receives research funding and honoraria from Novartis and Apotex, and is a consultant to Novartis.
Vitamin D might be worsening the cardiac iron overload and dysfunction by modulating calcium signaling. DR. WOOD