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 -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 -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/Eratio (E Doppler mitral fast inflow to the corresponding tissue Doppler E) continually increased with age (P<0.05) and reached levels indicating left ventricular diastolic dysfunction (E/E>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. (c) 2013 Wiley Periodicals, Inc.