Absence of echocardiographic cardiac involvement in treated hereditary haemochromatosis despite biochemical iron overload
T Prata Branco, B Couto Viana, E Andrade, L Alves, J Conde Goncalves, E Oliveira, M Rocha, H Moreira, P Mangas Palma, A Pinho, R Campos Costa, A Machado, R Lopes, C Sousa, R RodriguesAbstract
Background
Hereditary haemochromatosis (HH) may lead to myocardial iron deposition and subsequent structural and functional cardiac alterations. However, in contemporary clinical practice, many patients are diagnosed early and effectively treated, and the relationship between biochemical markers of iron overload and echocardiographic findings remains uncertain.
Purpose
To assess the association between biochemical markers of iron overload and echocardiographic parameters in patients with HH.
Methods
We conducted a cross-sectional study including 48 patients with genetically confirmed HH who underwent transthoracic echocardiography. Demographic, clinical, therapeutic and biochemical data (serum ferritin and transferrin saturation) were collected, together with echocardiographic parameters of left ventricular systolic function, diastolic function and ventricular geometry. Correlation analyses were performed to evaluate associations between iron overload markers and echocardiographic variables.
Results
Mean age was 57.8 years, 72% were male and mean body mass index was 27.6 kg/m². Hypertension was present in 47%, diabetes in 22%, chronic liver disease in 12.5% and significant alcohol consumption in 19%. Coronary artery disease was observed in 3.1% and atrial fibrillation in 12.5%. Most patients were treated with phlebotomy (87.5%), while 6.3% received iron-chelating therapy. Median ferritin level was 418.3 ng/mL and median transferrin saturation was 41%. The median interval between HH diagnosis and echocardiographic evaluation was 3 years, and 78% of patients had only one echocardiographic assessment. Left ventricular systolic function was preserved in 87.5% of patients, with a median left ventricular ejection fraction of 57.5%. Ventricular geometry was normal in 50%, while 28% showed concentric remodelling, 12.5% concentric hypertrophy and 9.5% eccentric hypertrophy. Diastolic function was normal in 72%, with Grade I dysfunction in 9% and Grade II in 19%; no Grade III dysfunction was identified. No significant associations were found between ferritin or transferrin saturation and any echocardiographic parameter.
Conclusion
In this cohort of predominantly treated patients with HH, biochemical iron overload was not associated with echocardiographic evidence of cardiac involvement. These findings suggest that early diagnosis and effective iron-depleting therapy may prevent or delay the development of structural and functional myocardial changes detectable by conventional echocardiography. Importantly, serum ferritin and transferrin saturation did not identify patients with subclinical cardiac abnormalities, questioning their value as standalone tools for cardiac risk stratification in this setting. Prospective longitudinal studies incorporating serial imaging and advanced modalities are needed to determine whether cardiac involvement emerges later and to define optimal strategies for cardiological surveillance in hereditary haemochromatosis.