The pathophysiological relationship and clinical significance of left atrial function and left ventricular diastolic dysfunction in β‐thalassemia major

Iron deposition in combination with inflammatory and immunogenetic factors is involved in the pathophysiology of cardiac dysfunction in β-thalassemia major. We investigated the mechanical and endocrine function of the left atrium and ventricle to identify early signs of dysfunction. We studied 90 patients (mean age: 29 ± 11 years) with β-thalassemia and normal left ventricular function and 90 age and sex-matched healthy controls. Patients and controls underwent a thorough cardiac echocardiographic study and measurements of the b-type (NT-proBNP) and atrial natriuretic peptides (proANP). Patients underwent 24-hr Holter recordings for arrhythmia monitoring. In the patient group, atria were affected early during the course of the disease, prior to diastolic and systolic left ventricular dysfunction. The E/E′ratio (E Doppler mitral fast inflow to the corresponding tissue Doppler E) continually increased with age (P   15) in the third decade whereas indexes of active and passive atrial function decreased gradually throughout life. In controls, the E/E′ ratio continually increased with age but with later (fifth decade) appearance of diastolic dysfunction and a compensatory increase in atrial active function. Both natriuretic peptides were significantly increased in patients compared to controls (558 ± 141 and 2,580 ± 1,830 fmol/mL for NT-proBNP and proANP versus 332 ± 106 and 1,331 ± 1,134 fmol/mL, respectively). Atrial fibrillation was found in a subgroup of 23 (26%) patients, older in age with mild diastolic function and enlarged, depressed atria. In conclusion, atrial mechanical depression seems to be a very early sign of cardiac damage. It may become echocardiographically evident even before diastolic and systolic dysfunction and is associated to supraventricular arrhythmias. Am. J. Hematol. 89:13–18, 2014. © 2013 Wiley Periodicals, Inc.