Role of non-invasive assessment in prediction of preclinical cardiac affection in multi-transfused thalassaemia major patients.

BACKGROUND: The principal cause of mortality and morbidity in ß-thalassemia major (ß-TM) is the iron overload as these patients receive about 20 times the normal intake of iron, which leads to iron accumulation and damage in the liver, heart, and endocrine organs. Chronically transfused patients used to die from cardiac iron overload in their teens and twenties. Monitoring of iron status through cardiac magnetic resonance imaging (CMRI) has replaced the conventional methods of assessment, yet this modality is not readily available in centers where the disease distribution is maximal. Objectives The aim of this work is to study some simple non-invasive tools and their abilities to predict preclinical cardiac affection reflecting cardiac iron deposition (CID) in multi-transfused ß-TM patients taking the T2* CMRI as a gold standard reference test. METHODS: One hundred consecutive multi-transfused, clinically stable ß-TM patients with age ranging from 16 to 30 years (mean ± SD, 21.1 ± 3.9) were included in this study. Assessment of serum ferritin, serum hepcidin, and high-sensitivity C-reactive protein as well as cardiac assessment by echo-doppler and 24-hour Holter were used to predict CID, and consequently predict preclinical cardiac affection, in reference to CMRI results as the standard method of cardiac iron assessment. RESULTS: According to CMRI results, patients were subdivided into a group of 42 patients with detectable myocardial iron (T*≤ 20 ms) and a group of 58 patients with no detectable myocardial iron (T* > 20 ms). No differences in age, gender, or distribution of splenectomized patients were observed between both groups. Patients with detectable myocardial iron received significantly higher number of transfusions per year than those with no detectable myocardial iron (mean ± SD, 14.6 ± 1.7 vs. 12.5 ± 1.7; P < 0.001) yet comparable levels of serum ferritin, serum hepcidin, and hepcidin/ferritin ratio (P > 0.05) were noted. Cardiac iron detection was associated with significantly lower heart rate (mean ± SD, 75 ± 6.1 vs. 80 ± 6.9; P < 0.001), lower left ventricular ejection fraction (LVEF) (mean ± SD 60.1 ± 3.2 vs. 70.1 ± 2.8; P < 0.001), and higher total number of premature ventricular contractions (PVCs) (median 78 vs. 14; P < 0.001). The group with CID comprised significantly more patients with left ventricular diastolic dysfunction (15/42, 35.7% vs. 3/58, 5.2%; P < 0.001); PVCs ≥10/hour (13/42, 31% vs. 2/58, 3.4%; P < 0.001); episodes of sinus pauses (6/42, 14.3% vs. 1/58, 1.7%; P < 0.05); episodes of high-grade atrio-ventricular block (5/42, 11.9% vs. 1/58, 1.7%; P < 0.05) compared to the group with no (CID). In presence of normal LVEF, detection of 10 or more PVCs per hour was the most predictive of cardiac iron loading with a positive predictive value of 86.7% and specificity of 96.6%, and the highest likelihood ratio (9.09). Detection of more than 22 PVCs/24 hours had the best sensitivity (81%) and the best negative predictive value (84%). The positive likelihood ratio of the studied parameters was highest in case of presence of PVCs ≥10/hour and lowest in case of average heart rate with a cut-off level of ≤77.5 bpm (9.09 and 1.46, respectively). CONCLUSION: Our results support our hypothesis that monitoring ß-TM patients with echo and Holter electrocardiogram can help in the detection of preclinical cardiac affection in centers lacking cardiac MRI; however, due to relatively low sensitivity they can not fully replace CMRI. Further work is needed to identify additional simple parameters that can form a diagnostic model with adequate sensitivity.

Plasma PTX3 levels in sickle cell disease patients, during vaso occlusion and acute chest syndrome (data from Saudi population).

BACKGROUND: Sickle cell disease (SCD) is a chronic, incurable hereditary disease. The vaso-occlusive crisis (VOC) is the most frequently occurring acute complication in sickle cell patients and accounts for the majority of SCD-related hospital admissions. Another major complication is the potentially fatal acute chest syndrome (ACS). The prototypic long pentraxin-3 (PTX3), an acute phase protein and a key component of innate immunity, is linked to ischemia-induced inflammation, a condition incriminated in SCD complications. AIM: To investigate the expression of PTX3 in stable SCD and VOC patients and to assess its relation to the development and progression of ACS. SUBJECTS AND METHODS: We conducted this study on 160 patients with confirmed SCD (20 stable SCD and 140 in VOC), and 10 healthy age- and sex-matched controls. Patients were diagnosed as SCD by high-performance liquid chromatography. PTX3 levels were assessed using enzyme-linked immunosorbant assay. RESULTS: In the stable state, all 20 SCD patients had PTX3 levels (range = 0.9-2.1 ng/ml; median = 1.1) comparable to those of healthy controls (range = 0.8-2.0 ng/ml; median = 1.0) (P > 0.05). During the VOC, plasma PTX3 significantly increased (range = 8.7-37.2 ng/ml; median = 22.3) (P < 0.01). Out of 140 VOC patients, 15 (10.7%) developed ACS and four required mechanical ventilation, of which two died. The median plasma level of PTX3 (22.3 ng/ml) was set as a cut-off value to stratify patients into low- and high-PTX3 expressers. Of the 140 VOC patients, 43 (30.7%) had PTX3 levels >22.3 ng/ml, of these, 13 patients developed ACS (13/43; 30.2%); of the remaining 97 patients who had PTX3 ≤22.3 ng/ml, only two patients (2/97; 2.1%) progressed to ACS, with a further increment in PTX3 in all of them. PTX3 levels were correlated with length of hospital stay in VOC patients and markers of lung injury in ACS patients. CONCLUSION: PTX3 levels were higher in SCD patients in VOC, being associated with longer hospital stay. Higher initial PTX3 concentrations were related to the development of ACS with a further increase in PTX3 levels observed upon progression to ACS. Thus, PTX3 could be used as a subjective method to predict occurrence and severity of SCD acute complications.