Braggio M; Department of Diagnostics and Public Health, Verona, Italy.
Ceolan J; Minoia A; Villaboni S; Mazzi F; et al

BACKGROUND: Transfusion-dependent beta-thalassemia (TDT) is characterized
by reduced exercise capacity due to chronic hemolytic anemia, iron
overload cardiomyopathy, and potential skeletal muscle alterations. Early
cardiovascular and muscular dysfunction in the absence of cardiac iron
overload remains poorly characterized.

METHODS: In this exploratory study, 9 TDT patients without cardiac iron
overload and with normal body mass index (BMI) were matched with 9 healthy
controls. Cardiopulmonary exercise testing combined with lung ultrasound
(LUS-CPET) was used to assess exercise-induced lung congestion and
diastolic dysfunction. Serum biomarkers of endothelial activation (ICAM-1)
and muscle-metabolic function (FGF21, miR-577) were evaluated. Resting
echocardiography, handgrip strength, and body composition by bioelectrical
impedance analysis (BIA) were also assessed.

RESULTS: At rest, cardiac output and diastolic function were comparable
between groups. However, during LUS-CPET, TDT patients exhibited
significantly lower VO2max, O2 pulse, and chronotropic index, along with
increased B-lines, consistent with exercise-induced diastolic dysfunction.
TDT patients also showed reduced lean body mass and handgrip strength.
FGF21 levels were elevated at rest and post-exercise, whereas miR-577
levels were reduced. Post-exercise ICAM-1 levels were significantly higher
in TDT patients compared to controls.

CONCLUSIONS: LUS-CPET may represent a useful non-invasive approach to
identify early exercise-induced diastolic dysfunction in TDT patients
without cardiac iron overload. Altered FGF21 and miR-577 profiles suggest
the presence of metabolic dysregulation associated with early skeletal
muscle deconditioning.