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

Abstract

Iron deposition in combination with inflammatory and immunogenetic factors is involved in the pathophysiology of cardiac dysfunction in b-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 6 11 years) with b-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 (NTproBNP) 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 0 ratio (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 0 > 15) in the third decade whereas indexes of active and passive atrial function decreased gradually throughout life. In controls, the E/E 0 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 6 141 and 2,580 6 1,830 fmol/mL for NT-proBNP and proANP versus 332 6 106 and 1,331 6 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.

Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

“…ECG recording could be used by hematologists as a screening tool in those patients. Iron deposition, microvascular scarring combined with inflammatory and immunogenetic factors, endocrine deficiencies, chronically elevated cardiac output secondary to anemia, increased cardiac afterload due to accelerated vascular aging, and the hypercoagulability state are involved in the pathophysiology of cardiac dysfunction in beta-thalassemia major [ 84 , 85 , 90 , 91 ]. Within cells, iron catalyses the production of reactive oxygen species, causing lipid peroxidation and organelle damage [ 85 ].…”

“…Within cells, iron catalyses the production of reactive oxygen species, causing lipid peroxidation and organelle damage [ 85 ]. Atrial mechanical depression was reported as a very early sign of cardiac damage in beta-thalassemia, prior to diastolic and systolic left ventricular dysfunction [ 91 ]. Males and females are at the same risk of accumulating iron in their hearts, but women better tolerate iron toxicity, probably due to a more effective antioxidant defense, a slower metabolic rate, more active immune function, and reduction in the activity of growth hormone [ 92 ].…”

Atrial fibrillation in β-thalassemia Major Patients: Diagnosis, Management and Therapeutic Options

“…In the first studies, its prevalence was around 10.0% [7,8] but that has reached up to 33.8% in recent times [11,13,26]. This increase should alarm β-TM specialists.…”

“…Thanks to transfusions and iron chelation, the prognosis of β-TM has dramatically improved, and recent studies have shown that the 80.0% of patients in countries with modern therapies available, survive to over 40 years of age [6,7]. A further improvement of survival for these patients is to be expected from an earlier commencement of chelation therapy and, in the near future, with the introduction of new drugs such as Luspatercept and genetic therapy.…”

“…Heart failure usually develops in patients with non optimal chelation therapy and multiendocrinopathies. The incidence of iron overload cardiomyopathy ranges from 11.4 to 15.1% in β-TM patients [7,8]. Restrictive cardiomyopathy usually occurs first followed by dilatation, in accordance with diastolic dysfunction, which normally precedes systolic dysfunction and overt heart failure.…”