The clinical value of ficolin-3 gene polymorphism in rheumatic heart disease. An Egyptian adolescents study.

OBJECTIVE: Ficolin-3 is one of the innate immunity molecules that was thought to play a pivotal role in Streptococcus pyogenes autoimmunity and its complications; rheumatic fever (RF) and rheumatic heart disease (RHD). We aimed to disclose if there is an association between ficolin-3 (FCN3) gene polymorphisms (rs4494157 and rs10794501) and RF with or without RHD for the first time in Egyptian adolescents. RESULTS: Serum ficolin-3 level was significantly elevated in patients suffering from RF with and without RHD in comparison with control. Regarding FCN3 gene (rs4494157) polymorphism, a significant correlation was found between the A allele and the susceptibility to RF with or without RHD (OR = 2.93, P = 0.0002 and OR = 2.23, P = 0.008 respectively). Besides, AA homozygous genotype showed a significant association with RHD risk (OR = 3.47, P = 0.026). Patients carrying the A allele (CA + AA) had significantly higher serum ficolin-3 than those carrying the CC genotype (P ˂ 0.0001). While the frequency of (rs10794501) polymorphism revealed no significant differences between the controls and RF patients with or without RHD (OR = 1.43, P = 0.261 and OR = 1.48, P = 0.208 respectively).

New guidelines for diagnosis of rheumatic fever; do they apply to all populations?

BACKGROUND AND OBJECTIVES: To evaluate the efficacy of recently updated Jones criteria for diagnosis of rheumatic fever in high incidence populations like Egypt. METHODS: Clinical data of 891 Egyptian patients with rheumatic fever, aged 5-15 years in a highly specialized rheumatic fever clinic were reviewed retrospectively from March 2014 to March 2016. Discriminant analysis was used to detect the most effective predictors for diagnosis of rheumatic fever in our patients incorporating echocardiographic criteria. We compared our results to the most recent update by the American Heart Association. RESULTS: The most effective predictors of rheumatic fever included arthritis, carditis, chorea, aortic regurgitation, grades of mitral regurgitation ≥10mm length and velocity ≥2.5 m/s, thick anterior mitral valve leaflets, elevated acute phase reactants, positive family history and prolonged PR interval. Our predictors showed a high sensitivity of 93%, a specificity of 62% and an overall prediction accuracy of 81.4%. CONCLUSION: We concluded that strict application of updated Jones criteria may lead to under diagnosis of rheumatic fever in highly endemic countries. We recommend further studies to examine the sensitivity of the most recent update of Jones criteria on other highly endemic populations.

Experience with balloon pulmonary valvuloplasty and predictors of outcome: a ten-year study.

BACKGROUND: Balloon pulmonary valvuloplasty is the treatment of choice for patients with moderate to severe pulmonary valve stenosis. METHODS: An observational retrospective cross-sectional study including neonates, small infants, and children who underwent balloon pulmonary valvuloplasty in the period from 2007 to 2016 in the cardiac catheterisation unit of the paediatric cardiology department in Cairo University. Multivariable models were built to report the predictors of the outcome of balloon pulmonary valvuloplasty and its complications. RESULTS: A total of 1200 patients were included in the study and divided according to age into 3 groups: neonates and early infants (n = 282), infants (n = 362), and children (n = 556). Procedural success, defined as a drop pressure gradient across the pulmonary valve to less than or equal to 50% of the baseline measurements, was achieved in 82.7% of the patients. Multivariate analysis revealed that only infundibular pulmonary stenosis (p value 0.032), supravalvular in association with valvular pulmonary stenosis (p value <0.001), and pulmonary valve diameter by angiogram (p value <0.001) were significant predictors of success. The presence of supravalvular in association with valvular pulmonary stenosis (p value <0.001) was associated with a lower weight (p value 0.007) and higher right ventricular pressure before the intervention (p value <0.001), and a minor immediate drop in the pressure gradient post-intervention (p value <0.001) was found to be the most significant predictor of the occurrence of complications. CONCLUSION: The absence of infundibular and supravalvular stenosis and a large pulmonary valve diameter were the most significant predictors of success.

Off-label use of duct occluder devices to close hemodynamically significant perimembranous ventricular septal defects: A multicenter experience.

OBJECTIVE: We sought to evaluate the feasibility, technical aspects, and outcome of transcatheter perimembranous ventricular septal defect (pmVSD) closure using duct occluder devices with a single retention disc. BACKGROUND: Use of duct occluder devices to close pmVSD seems a promising alternative therapy. However, limited data exist on this technique. METHODS: From 2010 to 2016, 222 patients (female 47.7%) were identified from databases of five participating institutions in whom pmVSD closure was attempted using an Amplatzer Duct Occluder I or Lifetech duct occluder device. RESULTS: Patients ranged in age from 0.7 to 52 years (median, 7.0 years) and in weight from 4.0 to 70 kg (median, 18.0 kg). The mean size of the VSD was 6.8 ± 2.2 mm. A large defect (> 6 mm) was present in 137 patients (61.7%). Device closure was successful in 218 patients (98.2%). The 10/8 mm device was used in most patients (n = 85, 38.3%), and the vascular approach was from the femoral vein in 169 patients (76.1%). There were 18 early complications in 17/218 patients (7.8%). Three patients (1.4%) developed complete heart block (transient n = 2; requiring permanent pacing n = 1). Median follow-up was 6 months (6 months-6 years). A mild residual shunt was seen in 10 patients at 6 months follow-up. CONCLUSIONS: The immediate results of transcatheter pmVSD closure using a duct occluder device with a single retention disc are promising. It is an effective technique with a lower rate of complications than for other currently available devices.

MBL2 gene polymorphism rs1800450 and rheumatic fever with and without rheumatic heart disease: an Egyptian pilot study.

BACKGROUND: Rheumatic fever (RF) is the result of an autoimmune response to pharyngitis caused by infection with Streptococcus pyogenes. RF is most prevalent in Africa and the Middle East. Rheumatic heart disease (RHD) is the most serious complication of RF. Mannose-binding lectin 2 gene (MBL2) has been reported to be correlated with different cardiac conditions. In Egyptian patients as a new studied ethnic population, it is the first time to evaluate the association between MBL2 gene polymorphism rs1800450 and RF with and without RHD. METHODS: One hundred and sixty RF patients (80 with RHD and 80 without RHD) and eighty healthy ethnically matched controls were studied. MBL2 (rs1800450) was genotyped by real-time PCR using TaqMan® allele discrimination assay. The MBL level was measured by ELISA. Westergren erythrocytes sedimentation rate (ESR), anti-streptolysin O titer (ASOT), C-reactive protein (CRP) and complements (C3 and C4) were determined. RESULTS: The AA genotype with high production of MBL was associated with increased risk of RHD more than the B allele carrying subjects. However, MBL2 genotype related to the low production of MBL was more frequently observed in those patients without RHD. CONCLUSIONS: Our results suggested the involvement of MBL2 (rs1800450) polymorphism and its protein in RHD pathogenesis. Also, it might be a promising future strategy to utilize this polymorphism to help differentiate patients with RHD from those without RHD.

The impact of growth factors on human induced pluripotent stem cells differentiation into cardiomyocytes.

Human induced pluripotent stem cells (hiPSCs) act as a promising therapeutic alternative for cardiovascular diseases. They yield a large number of functional cardiomyocytes (CMs) from autologous cell sources without ethical or immunological problems. However, significant limitations still remain in terms of line-to-line variability in CM yield and reproducibility. AIM: To efficiently enhance NP0040 hiPSCs differentiation into CMs. MAIN METHODS: Following a standard cardiac differentiation protocol using small molecules targeting the canonical Wnt signaling, growth factors (BMP4 and FGF2) and ascorbic acid were added further in order to increase the cardiac differentiation efficiency. All cultures were conducted in serum-free, feeder-free monolayer system followed by lactate purification. KEY FINDINGS: Using NP0040 hiPSCs, the CM yield resulting from modulation of the Wnt signaling pathway alone was inefficient compared to previous studies while the addition of BMP4, FGF2 and ascorbic acid resulted in enhanced cardiac differentiation outcome. The later resulted in a high yield (up to 92%) of cardiac troponin-T (cTnT) + CMs contracting spontaneously as organized sheets in 15 independent experiments. They were validated structurally and functionally using immunofluorescent staining for sarcomeric α-actinin, cTnT, MLC2v and Connexin 43. Reverse-transcriptase PCR revealed cardiac transcription factors and cardiac-specific genes expression. CMs were electrically connected to one another. Recorded action potential (AP) showed waves of relatively mature ventricular-like phenotype. SIGNIFICANCE: We demonstrated that hiPSC lines respond differently to a standard cardiac differentiation protocol and that a well-orchestrated interplay between Wnt, BMP4, FGF/MEK and Ascorbic acid MEK/ERK1/2 signaling pathways is beneficial in enhancing the differentiation outcome.

Echocardiographic changes and growth retardation in a group of Egyptian children with rheumatic heart disease.

BACKGROUND: Advances in echocardiographic studies have identified a massive burden of rheumatic heart disease (RHD) which continues to be a major health hazard in most developing countries. The aim of this study was to investigate the correlation between cardiac affection as regards the presence of single or multiple valvular lesions, and their severity and the growth parameters in a group of Egyptian children with RHD. METHODS: This study is a cross-sectional study, that was conducted on 200 children with RHD and 400 age-matched healthy. All subjects were subjected to anthropometric measurement and echocardiographic evaluation of the different cardiac parameters. RESULTS: Isolated mitral incompetence (MI) was the most frequent type of valvular lesion in RHD (54.0%), followed by mixed MI and aortic incompetence (AI) (26.5%). Patients with RHD were more liable to be underweight and stunted compared to controls (P<0.05). Growth retardation was significantly noticed in patients with RHD in general (P<0.05), and particularly in patients mixed MI and AI in particular (P<0.05). Also a significant association was detected between growth retardation and the severity of the valvular lesion in the group of rheumatic heart patients (P<0.05). CONCLUSIONS: Associations between growth retardation and RHD with its various patterns of valvular affection and severity were detected in the present study.

Association of ficolin-2 (FCN2) functional polymorphisms and protein levels with rheumatic fever and rheumatic heart disease: relationship with cardiac function.

INTRODUCTION: A role for ficolin (FCN) 2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested. The aim of the study was to evaluate a possible relationship between single nucleotide polymorphisms located at positions -602 and -4 of the FCN2 gene and FCN2 serum levels and risk of development of rheumatic fever (RF) and rheumatic heart disease (RHD). MATERIAL AND METHODS: Seventy-seven Caucasian Egyptian patients with RF were recruited with a control group of 43 healthy subjects. DNA was extracted for analysis of the FCN2 gene at positions -602 and -4 and serum protein level was measured by ELISA. RESULTS: FCN2 AA genotype at the -4 position was more frequently observed in RF and RHD patients, as compared to healthy subjects (p = 0.005 and p = 0.013, respectively); furthermore, the A allele was identified as a possible risk factor for the development of RF (p = 0.023, OR = 1.852, 95% CI: 1.085-3.159). The haplotype -602/-4 G/A, which was associated with low median levels of L-ficolin, was observed more frequently in the RF group when compared to the healthy subjects (74/162, 48.1% vs. 29/420, 33.7%, OR = 1.834, 95% CI: 1.034-3.252, p = 0.038). Low serum ficolin-2 level was associated with ESV and EDV increases. FCN 2 level was significantly lower with AA genotypes than GG+AG genotypes of the -4 position (56.68 ±17.90 vs. 66.05 ±18.79, p = 0.008). CONCLUSIONS: Polymorphisms linked to low levels of L-ficolin may render an individual at risk of recurrent and/or severe streptococcal infection. The -4 AA genotype and -602/-4 G/A haplotype are possible risk factors for the development of carditis.

Predictors of transient left ventricular dysfunction following transcatheter patent ductus arteriosus closure in pediatric age.

OBJECTIVES: To evaluate the left ventricular function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure, and to identify the predictors of myocardial dysfunction post-PDA closure if present. INTERVENTIONS: Transcatheter PDA closure; conventional, Doppler, and tissue Doppler imaging; and speckle tracking echocardiography. OUTCOME MEASURES: To determine the feasibility and reliability of tissue Doppler and myocardial deformation imaging for evaluating myocardial function in children undergoing transcatheter PDA closure. PATIENTS AND METHODS: Forty-two children diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler, and tissue Doppler imaging, and speckle-derived strain rate echocardiography were performed at preclosure and at 48 hours, 1 month, and 6 months postclosure. Tissue Doppler velocities of the lateral and septal mitral valve annuli were obtained. Global and regional longitudinal peak systolic strain values were determined using two-dimensional speckle tracking echocardiography. RESULTS: The median age of the patients was 2 years and body weight was 15 kg, with the mean PDA diameter of 3.11 ± 0.99 mm. M-mode measurements (left ventricular end diastolic diameter, left atrium diameter to aortic annulus ratio, ejection fraction, and shortening fraction) reduced significantly early after PDA closure (p < 0.001). After 1 month, left ventricular end diastolic diameter and left atrium diameter to aortic annulus ratio continued to decrease, while ejection fraction and fractional shortening improved significantly. All tissue Doppler velocities showed a significant decrease at 48 hours with significant prolongation of global myocardial function (p < 0.001) and then were normalized within 1 month postclosure. Similarly, global longitudinal strain significantly decreased at 48 hours postclosure (p < 0.001), which also recovered at 1 month follow-up. Preclosure global longitudinal strain showed a good correlation with the postclosure prolongation of the myocardial performance index. CONCLUSION: Transcatheter PDA closure causes a significant decrease in left ventricular performance early after PDA closure, which recovers completely within 1 month. Preclosure global longitudinal strain can be a predictor of postclosure myocardial dysfunction.

Cardioprotective Effects of Wharton Jelly Derived Mesenchymal Stem Cell Transplantation in a Rodent Model of Myocardial Injury.

BACKGROUND: Whartons jelly-derived mesenchymal stem cells are a valuable alternative source that possess multipotent properties, easy to obtain and available in large scale compared to BMMSCs. We investigated the possibility of cardiac function improvement post isoproterenol induced cardiac injury in a rat model following human WJMSCs transplantation. MATERIALS AND METHODS: MSCs were extracted and cultured from cord WJ, characterized by morphology, Immunophenotyping and differentiation to osteoblast and adipocytes. WJMSCs were labeled with PKH2 linker dye. Wistar rats were divided into control group, ISO group (injected with 2 doses of isoproterenol) to induce myocardial injury and ISO group transplanted with labelled WJMSCs. ECG, electrocardiographic patterns, cardiac marker enzymes, tracing of labeled MSCs and immunohistochemical analysis of myocardial cryosections were studied. RESULTS AND CONCLUSIONS: WJ derived MSCs were expanded for more than 14 passages while maintaining their undifferentiated state, were positive for MSC markers and were able to differentiate into adipocyte and osteoblast. We demonstrated that intravenously administered WJMSCs were capable of homing predominently in the ischemic myocardium. Cardiac markers were positively altered in stem cell treated group compared to ISO group. ECG and ECHO changes were improved with higher survival rate. WJMSCs could differentiate into cardiac-like cells (positive for cardiac specific proteins) in vivo. WJMSCs infusion promoted cardiac protection and reduced mortality, emphasizing a promising therapeutic role for myocardial insufficiency.

Acute Kawasaki disease with emphasis on the echocardiographic profile: A single center experience.

Background: Echocardiographic features of acute Kawasaki disease (KD) have not been well characterized in Egyptian children. This study aimed to provide insight into the pattern of cardiac involvement in Egyptian children with Kawasaki disease, focusing on echocardiographic coronary abnormalities and their associated risk predictors. Methods and Results: Medical records of 64 KD patients from 2012 to 2016 were retrospectively analyzed with recalculation of coronary artery z-scores during the first eight weeks after fever onset. All patients received intravenous immunoglobulin (IVIG) and 57.8% were treated within 10 days of illness onset. Coronary abnormalities were found in 53.1% of all patients, and in 43.2% of those who received IVIG within 10 days. Giant aneurysms (z-score>10) comprised 23.5% of all coronary abnormalities. Coronary thrombosis occurred in two patients (5%), both of whom developed myocardial infarction, and one succumbed to heart failure with eventual in-hospital death. Overall, 7% of patients had mitral regurgitation (n = 5), 1.5% had aortic regurgitation (n = 1), and 7.8% had pericardial effusion (n = 5). Among a number of laboratory and clinical predictors, platelet count had the strongest association with coronary abnormalities (Area under Receiver-operating characteristic (ROC) curve: 0.794; 95% confidence interval 0.678-0.910; P < 0.001). Conclusion: Coronary abnormalities occur in a substantial percentage of KD in Egypt, with associated evidence of severe inflammation. Further efforts are required to increase awareness of the disease and to emphasize the importance of early IVIG administration. Future studies should also be undertaken to characterize the long term progression profile of the disease as well as the possible genetic background of the disease in Egypt.

Incomplete RV Remodeling After Transcatheter ASD Closure in Pediatric Age.

Published data showing the intermediate effect of transcatheter device closure of atrial septal defect (ASD) in the pediatric age-group are scarce. The objective of the study was to assess the effects of transcatheter ASD closure on right and left ventricular functions by tissue Doppler imaging (TDI). The study included 37 consecutive patients diagnosed as ASD secundum by transthoracic echocardiography and TEE and referred for transcatheter closure at Cairo University Specialized Pediatric Hospital, Egypt, from October 2010 to July 2013. Thirty-seven age- and sex-matched controls were selected. TDI was obtained using the pulsed Doppler mode, interrogating the right cardiac border (the tricuspid annulus) and lateral mitral annulus, and myocardial performance index (MPI) was calculated at 1-, 3-, 6- and 12-month post-device closure. Transcatheter closure of ASD and echocardiographic examinations were successfully performed in all patients. There were no significant differences between two groups as regards the age, gender, weight or BSA. TDI showed that patients with ASD had significantly prolonged isovolumetric contraction, relaxation time and MPI compared with control group. Decreased tissue Doppler velocities of RV and LV began at one-month post-closure compared with the controls. Improvement in RVMPI and LVMPI began at 1-month post-closure, but they are still prolonged till 1 year. Reverse remodeling of right and left ventricles began 1 month after transcatheter ASD closure, but did not completely normalize even after 1 year of follow-up by tissue Doppler imaging.

Regression of a large congenital hepatic arteriovenous malformation.

Congenital hepatic arteriovenous malformations are rarely seen in association with persistent neonatal pulmonary hypertension. We report the case of a full-term female newborn who presented with heart failure and respiratory distress soon after birth. Echocardiographic investigation revealed severe persistent pulmonary hypertension and patent ductus arteriosus. Here we report spontaneous regression in size of both the feeder vessel and the vascular bed of the congenital hepatic arteriovenous malformation. We postulate that our conservative use of oral heart failure therapy, in the form of diuretic agents and captopril, decreased the congestion and diameter of the affected vessels.

Gene expression profiling of endometrium versus bone marrow-derived mesenchymal stem cells: upregulation of cytokine genes.

Postulated Stem/progenitor cells involved in endometrium regeneration are epithelial, mesenchymal, and endothelial. Bone marrow (BM) has been implicated in endometrial stem cells. We aimed at studying gene expression profiling of endometrial mesenchymal stem cells compared to BM MSCS to better understand their nature and functional phenotype. Endometrial tissues were obtained from premenopausal hysterectomies (n = 3), minced and enzymatically digested as well as Normal BM aspirates (n=3). Immunophenotyping, differentiation to mesoderm, and proliferation were studied. The expression profile of 84 genes relevant to mesenchymal stem cells was performed. Fold change calculations were determined with SA Biosciences data analysis software. VEGF, G-CSF, and GM-CSF in cultures supernatants of MSCs were assayed by Luminex immunoassay. Endo MSCs possess properties similar to BM MSCs. Cumulative population doubling was significantly higher in Endo MSCs compared to BM MSCs (p < 0.001). 52 core genes were shared between both generated MSCs including stemness, self-renewal, members of the Notch, TGFB, FGF, and WNT.16 downregulated genes (VCAM, IGF1)and 16 upregulated in Endo MSCs compared to BM (p < 0.05 â†’ fourfolds). They included mostly cytokine and growth factor genes G-CSF, GM-CSF, VWF, IL1b, GDF15, and KDR. VEGF and G-CSF levels were higher in Endo MSCs supernatants (p < 0.0001). Cells sharing MSC and endothelial cell characteristics could be isolated from the human endometrium. Endo MSCs share a core genetic profile with BM MSCs including stemness. They show upregulation of genes involved in vasculogenesis, angiogenesis, cell adhesion, growth proliferation, migration, and differentiation of endothelial cells, all contributing to endometrial function.

Comparative characteristics of endothelial-like cells derived from human adipose mesenchymal stem cells and umbilical cord blood-derived endothelial cells.

Adult peripheral blood contains a limited number of endothelial progenitor cells that can be isolated for treatment of ischemic diseases. The adipose tissue became an interesting source of stem cells for regenerative medicine. This study aimed to investigate the phenotype of cells obtained by culturing adipose-derived mesenchymal stem cells (ad-MSCs) in the presence of endothelial growth supplements compared to endothelial cells obtained from umbilical cord blood (UCB). Passage 3 ad-MSCs and mononuclear layer from UCB were cultured in presence of endothelial growth media for 3 weeks followed by their characterization by flow cytometry and polymerase chain reaction. After culture in endothelial inductive media, ad-MSCs expressed endothelial genes and some endothelial marker proteins as CD31 and CD34, respectively. Adipose tissue could be a reliable source for easy obtaining, expanding and differentiating MSCs into endothelial-like cells for autologous cell-based therapy.

Evaluation of the policy of secondary prevention against rheumatic fever among Egyptian children.

OBJECTIVE: We evaluated the effectiveness of long acting penicillin (LAP) as a 2-weekly regimen in winter and a 3-weekly regimen in summer for prevention of streptococcal colonization and also studied the common complaints of patients during the period of compliance for LAP administration. We also attempted to determine the incidence of relapses or recurrence of rheumatic fever (RF) after the onset of first episode of RF. PATIENTS & METHODS: 210 rheumatic patients with good compliance to LAP (for at least one year) were included in the study. Demographic, clinical information, patients' complaints and echocardiographic data of rheumatic patients were collected both retrospectively and prospectively. Anti-streptolysin O titre (ASOT) and throat swab culture were done at the end of the study (on Day 14 in the 2-weekly regimen and on Day 21 in the 3-weekly regimen). RESULTS: The age of onset of rheumatic fever was mostly between 5 and 15 years and the youngest patient was 2 years old. Subclinical carditis (SCC) was present in 79 (37%) of all the patients in the study population. Only 7 patients (3.3%) had a relapse within 2 years of the acute episode of RF. At the end of the study, ASOT was found to be high only in 11 patients (5.2%) and throat swab cultures were found negative in all patients CONCLUSION: LAP regimen is fairly effective in eradicating streptococcal colonization. The incidence of relapse of RF within 2 years of the acute episode of RF is relatively low.

Stenting the arterial duct in neonates and infants with congenital heart disease and duct-dependent pulmonary blood flow: a multicenter experience of an evolving therapy over 18 years.

OBJECTIVES: The primary aim of this multi-institutional study was to describe our 18-year experience of ductal stenting (DS) in infants with a duct-dependent pulmonary circulation. The secondary aim sought to identify a subgroup of patients who may benefit the most using this evolving technique. BACKGROUND: No study has examined the extraordinary evolution of this promising therapy over the last two decades. METHODS: Between 1991 and 2009, 65 neonates and infants (39 male, 60%) underwent cardiac catheterization for DS in 3 participating centres. Patients were divided according to whether DS was attempted between 1991-2000 (Group 1, n = 20) or between 2001-2009 (Group 2, n = 45). RESULTS: DS was successful in 52/65 (80%) patients. DS outcome was associated with ductal morphology and cardiac diagnosis. DS failed more often in patients with univentricular physiology and tortuous duct morphology (p < 0.001). Most patients undergoing DS in Group 2 had pulmonary atresia with intact ventricular septum (PAIVS) (p < 0.001). DS was successful in 94% of these patients. Groups differed significantly in diameter and length of first implanted stent (p < 0.001), implanting additional stent (p < 0.001), and occurrence of complications (p = 0.033). Freedom from re-intervention for the 52 patients was 92.3%. No procedure-related mortality occurred. CONCLUSIONS: The technical aspects and clinical application of percutaneous DS has changed in the last two decades. DS has become a practical and safe therapy in a subgroup of neonates with ductal-dependent pulmonary blood flow.

Serial echocardiographic left ventricular ejection fraction measurements: a tool for detecting thalassemia major patients at risk of cardiac death.

Cardiac damage remains a major cause of mortality among patients with thalassemia major. The detection of a lower cardiac magnetic resonance T2* (CMR-T2*) signal has been suggested as a powerful predictor of the subsequent development of heart failure. However, the lack of worldwide availability of CMR-T2* facilities prevents its widespread use for follow-up evaluations of cardiac function in thalassemia major patients, warranting the need to assess the utility of other possible procedures. In this setting, the determination of left ventricular ejection fraction (LVEF) offers an accurate and reproducible method for heart function evaluation. These findings suggest a reduction in LVEF≥7%, over time, determined by 2-D echocardiography, may be considered a strong predictive tool for the detection of thalassemia major patients with increased risk of cardiac death. The reduction of LVEF≥7% had higher (84.76%) predictive value. Finally, Kaplan-Meier survival curves of thalassemia major patients with LVEF≥7% showed a statistically significant decreased probability of survival for heart disease (p=0.0022). However, because of limitations related to the study design, such findings should be confirmed in a large long-term prospective clinical trial.