Prevalence and clinical correlates of miocardial fibrosis and necrosis in thalassemia major patients by CMR-DE

Introduction

Cardiovascular Magnetic Resonance (CMR) by delayed enhancement (DE) has proven to visualize myocardial scarring, but no dedicated studies are available in thalassemia major.

Purpose

Aim of our study was to investigate the prevalence, extent, clinical and instrumental correlates of myocardial fibrosis or necrosis by DE CMR in thalassemia major patients.

Methods

115 thalassemia major patients (40 men, mean age 27 ± 8 years) were consecutively examined at our CMR Laboratory using a 1.5 T scanner (GE Excite). Steady-state free procession cines were acquired during 8-second breath holds in sequential 8-mm short axis slices from the atrio-ventricular ring to the apex to assess biventricular function. Biventricular function was quantitatively assessed using MASS^® software (Medis, Leiden, The Netherlands).

Contrast delayed enhanced images were acquired in the same view used for cine CMR from 10 to 15 minutes, after the Gadobutrol (1.0 mol/L) (0.2 mmoli/Kg) intravenous administration, using a fast gradient-echo inversion recovery sequence. Inversion times were adjusted to null the normal myocardium (from 210 ms to 300 ms) with voxel size of 1.6 × 1.25 × 8.0 mm. The extent of DE areas was quantified using semi-automatic, previously validated software (HIPPO DELAY^®).

Myocardial iron overload was determined by multislice multiecho T2*. Three parallel short-axis views of the left ventricle were obtained by T2* gradient-echo multiecho sequence. Global LV, mid-ventricular and segmental T2* values were obtained by a dedicated software (HIPPO MIOT^®). Image analysis provided the mapping of segmental data on 16 segments of the left ventricle, according to the standard AHA/ACC model.

A twelve lead ECG was performed within one month from CMR, in absence of clinical cardiovascular events and was read blindly by the consensus of two cardiologists who were unaware of the results of the CMR exam.

Results

DE areas were present in 28/115 patients (24%). Extent of DE was 3.9 ± 2.4%. In 26 patients the location of fibrosis was not specific and patchy distribution was prevalent. Two patients showed transmural DE following coronary distribution. The DE group was significantly older than the non-DE group (31 ± 7.7 years versus 26 ± 7.7 years, P = 0.004). DE correlated with cardiac risk factors (P = 0.01), history of cardiac complications (P = 0.001), and anti-HCV antibodies (P = 0.04). We did not find significant relation with heart T2* values and biventricular function. Figure 1 shows a thalassemia major patient with no myocardial iron overload (all 16 segments T2* values > 20 ms) (A) and transmural DE (black arrows) following coronary distribution in the apical region (B, C).

Figure 1

A significant correlation was found between the presence of DE and changes in ECG (ECG abnormal in DE group 22/28 patients and in no-DE group 30/87 patients; chi-square 14.9; P = 0.0001).

Conclusion

In thalassemia patients the significant presence of myocardial fibrosis/necrosis seems to be a time dependent process correlating with cardiovascular risk factors and cardiac complications. HCV infection could be a causal agent in the pathogenesis of myocardial scarring. ECG-changes showed a good accuracy in predicting myocardial scarring.