Management of Persistent Pulmonary Hypertension After Correction of Congenital Heart Defect with Autologous Marrow-Derived Mononuclear Stem Cell Injection into the Pulmonary Artery: A Pilot Study.

Pulmonary arterial hypertension (PAH) related to left-to-right shunt can progress to Eisenmenger syndrome, a serious and fatal disease that is not yet curable. This pilot study considered stem cell injection as a new treatment modality in persistent pulmonary hypertension after the correction of a congenital heart defect. Three patients with persistent pulmonary hypertension after ventricular septal defect repair were included in this pilot study for a clinical trial. Mononuclear stem cells derived from patients' bone marrow specimens were injected into the right and left pulmonary arteries via cardiac catheterization. The patients were followed over a 6-month period, with six-minute walk test, echocardiography and repeated angiography performed in the sixth month after treatment. The results of the study showed improvement of 40 m, 280 m and 100 m in 6-minute walk distance in patients 1 to 3, respectively. The peak PR gradient decreased 2, 5 and 9 mmHg by echocardiography, and mean PA pressure decreased 21, 22 and 9 mmHg by catheterization in patients 1 to 3, respectively. Pulmonary artery resistance decreased 4, 4.5 and 1.3 Wood units after 6 months of stem cell therapy in the three patients. No short-term complications were detected in this pilot trial, and all patients tolerated the procedure without any complications. Intrapulmonary artery injection of stem cells may have a role in the treatment of persistent PAH secondary to congenital heart disease. This procedure is feasible, with no significant complications, and this study can be considered as a platform for larger studies.

Japanese Kawasaki Disease Scoring Systems: Are they Applicable to the Iranian Population?

BACKGROUND: Kawasaki disease (KD) is the most frequent cause of coronary artery aneurysm (CAA) in children. This study tried to evaluate the accuracy of different KD scores developed for prediction of CAA, in an Iranian population. METHODS: This is a cross-sectional retrospective investigation on pediatric patients with a diagnosis of KD. Clinical manifestations, laboratory, and echocardiographic data were recorded. Five Kawasaki scores, including Kobayashi, Egami, Sano, Nakano, and Harada, were assessed and analyzed in relation to CAA and intravenous immunoglobulin (IVIG) resistance. RESULTS: During five years, we recruited 121 cases of KD under 13 years of age. The rates of CAA and IVIG resistance were 16.5%, and 13.2% respectively. The IVIG resistance group was significantly younger than responder patients. All five scores had low sensitivity in predicting CAA or IVIG resistant cases; the highest sensitivity pertained to the Harada score with 50% sensitivity and 59% specificity (the area under the curve: 0.545, with a 95% confidence interval: 0.423 to 0.667) in predicting CAA, which is lower than the usual acceptable criteria for a screening test. The specificity of all other scores were more than 85% in predicting CAA or IVIG resistance. Gender, fever before therapy and laboratory data showed no significant difference between the groups. CONCLUSION: The Kobayashi, Egami, Sano, Nakano and Harada scores have limited usefulness in the Iranian population to predict high risk patients for coronary artery involvement or IVIG resistance; in our study, age under one year was a risk factor for IVIG resistance.

Hemolysis and its outcome following percutaneous closure of cardiac defects among children and adolescents: a prospective study.

BACKGROUND: Transcatheter closure of intracardiac defects might be complicated by intravascular hemolysis. We evaluated hemolysis and its outcome after transcatheter closure of these defects. METHODS AND PATIENTS: All patients who underwent transcatheter closure of patent ductus arteriosus, ventricular septal defect and atrial septal defect were included in this prospective study. Clinical data were obtained before and after the catheterization. RESULTS: One hundred and thirty-eight patients were enrolled; and four (3%) patients developed intravascular hemolysis; while two cases had residual shunt and two other cases had not residual flow. Although residual shunt occurred in ten patients, only 2 of these cases developed hemolysis. Patent ductus arteriosus closure was done for one of these cases and the other one, underwent perimembranous ventricular septal defect closure. Moreover, hemolysis occurred after device closure of patent ductus arteriosus in 2 of the other patients with no residual shunt. In this study the hemolysis was eliminated by conservative management within 2 weeks although residual shunt continued in this time. We observed a decline in lactate dehydrogenase value after catheterization in comparison with precatheterization, which was mainly among ventricular septal defect patients that might be due to mild chronic hemolysis in these patients. CONCLUSION: Incidence of hemolysis after device closure was low, and occurred with and without residual flow and was eliminated by conservative management in 2 weeks, without the need for surgery, although the residual shunt was continued.

Noninvasive Assessment of Pulmonary Artery Pressure in Patients with Extracardiac Conduit Total Cavopulmonary Connection.

To assess quantitative measurement of mean pulmonary artery pressure (PAP) in extracardiac total cavopulmonary connection (TCPC) patients by noninvasive echocardiographic inferior vena cava collapsibility index (IVC-CI) and also correlation between the peripheral vein pressure and mean PAP. In 19 TCPC patients with at least 1-year follow-up after completion of TCPC, complete echocardiography including IVC-CI was recorded. All patients underwent cardiac catheterization for mean PAP pressure, peripheral vein pressure (PVP) and contrast study. Different cutoff points of mean PAP were analyzed, and based on the highest cutoff point, patients were categorized into two groups: mean PAP < 17 mmHg (acceptable) and > = 17 mmHg (high) for comparison analysis. Between 2006 and 2015, from 43 patients who had undergone TCPC, nineteen patients with a mean age 12.9 ± 6.6 years and mean follow-up time of 3.4 ± 1.9 years were included in this study. Mean PAP was 14.6 ± 3.97 (range 8-22 mmHg). Thirteen (68 %) patients had PAP < 17 mmHg. No significant statistical difference was detected with respect to age, sex, type of congenital heart disease and fenestration between these two groups. But, right ventricular dominancy was more prevalent in the high PAP group (50 % vs. 7.7 % P value 0.03). IVC-CI had a correlation with mean PAP (r 0.67, P < 0.001). IVC-CI < 21.8 % can predict PAP > = 17 mmHg with 83 % sensitivity and 100 % specificity. Regression analysis proposed an equation for PAP measurement: PAP (mmHg) = 20.2097-0.1796 × (IVC-CI), (r2 = 0.56). Peripheral vein pressure measurement also showed a good correlation with mean PAP and may be used to estimate PAP with the following equation: PAP (mmHg) = 0. 8675 × PVP, (r 0.90, P < 0.0001). In conclusion, IVC-CI as noninvasive and peripheral vein pressure measurement as a minimal invasive method may be useful for quantitative estimation of PAP in patients with extracardiac TCPC.

Persistent Truncus Arteriosus With Intact Ventricular Septum: Clinical, Hemodynamic and Short-term Surgical Outcome.

INTRODUCTION: Truncus arteriosus with intact ventricular septum is a rare and unique variant of persistent truncus arteriosus (PTA) which usually presents with central cyanosis and congestive heart failure in neonate and early infancy. Associated cardiac and non-cardiac anomalies may affect morbidity and mortality of these patients. CASE PRESENTATION: We describe clinical presentation, echocardiography and angiographic features of a 7-month old boy with PTA and intact ventricular septum who underwent surgical repair of the anomaly at our institution. Operative findings, surgical procedure and short-term outcome are reported. CONCLUSIONS: While our patient had systemic pulmonary arterial pressure at the time of complete surgical repair, it was improved after surgery.

Evaluation of left ventricular function by tissue Doppler and speckle-derived strain rate echocardiography after percutaneous ductus closure.

The aim of this study was to evaluate the left ventricular systolic and diastolic function before and after transcatheter percutaneous patent ductus arteriosus (PDA) closure. 21 children (age >6 months old) diagnosed with hemodynamically significant PDA underwent percutaneous PDA closure. Conventional, Doppler and tissue Doppler imaging and speckled-derived strain rate echocardiography were done at pre-closure, 1 day (early) and 1 month (late) post-closure. Mean age of the patients (female/male: 1.3) was 17.54 ± 24.7 months with the mean PDA diameter of 3.6 ± 0.8 mm. Systolic measures (ejection fraction, shortening fraction) reduced significantly early after PDA closure (P < 0.05). After 1 month, both improved significantly; ultimately, after 1 month no change was observed in systolic function measures compared with the pre-closure status. Early and late diastolic flow velocities of mitral (E M and A M) reduced considerably in early and late post-closure time (P < 0.05). Both early tissue Doppler early velocity of lateral mitral annulus (E'M) and early to late velocity ratio (E'M/A'M) of lateral mitral annulus decreased significantly (P = 0.02) in early post-closure. After 1 month, E'M increased considerably. (P = 0.01) but E'M/A'M had an insignificant rise (P > 0.05). E M/E'M ratio did not change in early post-closure but it had a considerable reduction in the subsequent month compared with the pre- and early post-closure (P < 0.001 for both occasions). Global and segmental longitudinal strain measures reduced significantly early after PDA closure (P < 0.05) but it improved remarkably in the subsequent month. Transcatheter PDA closure causes a significant decrease in left ventricular performance early after PDA closure which recovers completely within 1 month. Also PDA size can affect post-closure left ventricular function.

Role of speckle tracking echocardiography in the assessment of post-repair left ventricular function in patients with late presentation of anomalous origin of the left coronary artery from the pulmonary artery.

The aim of this study was to determine the left ventricular myocardial deformation and segmental myocardial dysfunction by speckle tracking echocardiography and tissue Doppler imaging among the operated patients with anomalous origin of the left coronary artery from the pulmonary artery. The study was conducted on 12 patients diagnosed with anomalous origin of the left coronary artery from the pulmonary artery, who had been operated upon between 2001 and 2013 at the medical centres of Shiraz University of Medical Sciences, Shiraz, Iran. The mean age of the patients at the time of surgical correction was 12.6 years ranging from 6 months to 43 years, and the duration of postoperative follow-up was between 1 and 12 years. Comparison of the strain rate between the patients with acceptable ejection fraction and the control group by tissue Doppler imaging showed significant differences between the two groups regarding the lateral wall (p<0.001), but not the septal wall of the left ventricle (p=0.65). Moreover, the strain values by the speckle tracking method revealed significant differences between the patient and the control group regarding the global strain (p=0.016) and anterior, lateral, and posterior segments of the left ventricle. Although postoperative conventional echocardiography revealed normal global left ventricular function with acceptable ejection fraction, abnormal myocardial deformation of the variable segments of the left ventricle with regional and global myocardial dysfunction were well defined by speckle tracking echocardiography.

Distribution and Protective Role of HLAB40 in Iranian Patients with Kawasaki Disease; a Report from Southern Iran.

OBJECTIVE: Kawasaki disease (KD) clinically presents as a systemic vasculitis syndrome with significant cardiovascular involvement. With different incidence among different ethnic groups, the role of certain human leukocyte antigens and their products has been considered as a crucial predisposing factor in the immune responses in this disease. METHODS: We determined the distribution of human leukocyte antigens type B for 90 Iranian patients with Kawasaki disease in order to evaluate a possible association between these antigens and this disease in our area. We used the polymerase chain reaction (PCR) sequence specific primers (PCR-SSP) technique for antigen typing. Distribution of these antigens for 89 healthy Iranians used as control. Findings : While 7 (3.9%) of our patients were positive for human leukocyte antigen type B 40(*), there were 18 (10.1%) subjects from the control group who had this antigen with statistically significant difference between patients and control group (CI= 95%, RR=1.15 and P= 0.02). Data were analyzed by Pearson chi-square test and Fisher's exact test. SPSS version 15 was used for statistical analysis and a P value less than 0.05 considered statistically significant CONCLUSION: The presence of higher frequency of allele type-B40(*) in the control group may represent a protective role for this antigen with resultant decreased susceptibility to KD in our area.

Accuracy of Doppler-derived estimation of pulmonary vascular resistance in congenital heart disease: an index of operability.

Pulmonary vascular resistance (PVR) is a critical and essential parameter during the assessment and selection of modality of treatment in patients with congenital heart disease (CHD) accompanied by pulmonary arterial hypertension (PAH). Cardiac catheterization is the "gold standard" but is an invasive method for PVR measurement. A noninvasive and reliable method for estimation of PVR in children has been a major challenge and most desirable during past decades, especially for those who need repeated measurements. In a prospective study and among consecutive patients who were referred for cardiac catheterizations, PVR was calculated as the ratio of the transpulmonary pressure gradient (∆P) to the amount of the pulmonary flow (QP) accordingly for 20 patients with CHD and high PAH. Subsequently and noninvasively, PVR was assessed for these patients by a Doppler echocardiography-derived index defined as the ratio of the tricuspid regurgitation velocity (TRV(m/s)) to the velocity time integral (VTI(cm)) of the right-ventricular outflow tract (RVOT). There was a good correlation between PVR measured at catheterization (PVR(cath)) and TRV/VTI(m) ratio; the mean of three measurements of VTI (VTI(m)) with R (2) = 0.53 (p = 0.008). In addition, a TRV/VTI(m) value of 0.2 provided a sensitivity of 71.4% and a specificity of 100% for PVR >6 Woods units (WU) as well as sensitivity of 90% and specificity of 90% for a PVR equal to 8 WU. PVR value between 6 and 8 WU by catheterization has been considered as a cut-off point for intervention in children with left-to-right shunts and PAH. In conclusion, Doppler-derived TRV/VTI(m) ratio is a reliable index that may be helpful as a supplementary diagnostic tool for the selection of modality of treatment and follow-up of patients with PAH and increased PVR.

Giant aneurysm of thoracic and proximal abdominal aorta in a patient with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency disease, predisposing the patients to various tissue involvement and organ damage. Here a 16-year-old boy is presented who was referred to our center with cough, dyspnea, cyanosis, and history of recurrent pneumonia. The diagnosis of CVID was made according to reduction all serum immunoglobulin levels, normal numbers of T, B and NK lymphocyte subpopulations, poor antibodies responses. Considering abnormality in heart examination and chest X-ray, echocardiography and computed tomography angiography were performed which showed large thoraco-abdominal aortic aneurysm in this patient. Although there are some reports of cardiovascular disease associated with primary antibody deficiencies, this is the first time that such large thoraco-abdominal aortic aneurysm is reported in CVID. This may be secondary to recurrent pulmonary infections or an unknown mutation process. Cardiovascular abnormalities are an entity that should be kept in mind in patients with primary immunodeficiency diseases.

Risk of nephropathy after consumption of nonionic contrast media by children undergoing cardiac angiography: a prospective study.

Despite increasing reports on nonionic contrast media-induced nephropathy (CIN) in hospitalized adult patients during cardiac procedures, the studies in pediatrics are limited, with even less focus on possible predisposing factors and preventive measures for patients undergoing cardiac angiography. This prospective study determined the incidence of CIN for two nonionic contrast media (CM), iopromide and iohexol, among 80 patients younger than 18 years and compared the rates for this complication in relation to the type and dosage of CM and the presence of cyanosis. The 80 patients in the study consecutively received either iopromide (group A, n = 40) or iohexol (group B, n = 40). Serum sodium (Na), potassium (K), and creatinine (Cr) were measured 24 h before angiography as baseline values, then measured again at 12-, 24-, and 48-h intervals after CM use. Urine samples for Na and Cr also were checked at the same intervals. Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal damage (RIFLE criteria) were used to define CIN and its incidence in the study population. Accordingly, among the 15 CIN patients (18.75%), 7.5% of the patients in group A had increased risk and 3.75% had renal injury, whereas 5% of group B had increased risk and 2.5% had renal injury. Whereas 33.3% of the patients with CIN were among those who received the proper dosage of CM, the percentage increased to 66.6% among those who received larger doses, with a significant difference in the incidence of CIN related to the different dosages of CM (p = 0.014). Among the 15 patients with CIN, 6 had cyanotic congenital heart diseases, but the incidence did not differ significantly from that for the noncyanotic patients (p = 0.243). Although clinically silent, CIN is not rare in pediatrics. The incidence depends on dosage but not on the type of consumed nonionic CM, nor on the presence of cyanosis, and although CIN usually is reversible, more concern is needed for the prevention of such a complication in children.

Effect of combination therapy of hydroxyurea with l-carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with beta-thalassemia intermedia.

BACKGROUND: l-Carnitine and magnesium have antioxidant properties. They have the potential to stimulate production of fetal hemoglobin and stabilize the RBC membrane, respectively. Several studies have also shown the beneficial effects of hydroxyurea in thalassemic patients. We assessed the effect of combination therapy of hydroxyurea with l-carnitine and magnesium chloride on hematologic parameters and cardiac function of patients with beta-thalassemia intermedia. METHODS: One-hundred-and-twenty patients with thalassemia intermedia (range, 4-35 yr; mean, 19 +/- 6.4 yr) who had no need for blood transfusion or requirement for blood transfusion with an interval of >6 months were randomly selected. All patients had been on hydroxyurea for >6 months. They were randomly divided into four groups: group A (hydroxyurea alone); group B (hydroxyurea and l-carnitine); group C (hydroxyurea and magnesium chloride); and group D (hydroxyurea, l-carnitine and magnesium chloride). RESULTS: In groups B, C, and D, mean Hb and hematocrit increased during 6-month treatment (P < 0.001). Echocardiographic studies revealed a significant decrease in left ventricular end-diastolic diameter in group B (P = 0.032), increase in pulmonary acceleration time in group C (P = 0.012), and increase in left ventricular ejection fraction in groups C and D (P < 0.000 and 0.006, respectively). CONCLUSION: Combination of hydroxyurea with l-carnitine or magnesium could be more effective in improving hematologic parameters and cardiac status in patients with beta-thalassemia intermedia than hydroxyurea alone.

Efficacy of Carvedilol in Patients with Dilated Cardiomyopathy due to Beta-thalassemia major; a Double-blind Randomized Controlled Trial.

OBJECTIVE: Dilated cardiomyopathy is the end result of chronic iron overload in patients with beta thalassemia major. The objective of the present study was to evaluate the safety and efficacy of Carvedilol in patients with beta thalassemia major and dilated cardiomyopathy. METHODS: During a six-month period, fourteen patients with beta-thalassemia major and heart failure without diabetes mellitus referred to pediatric cardiology clinic enrolled in this double blind, randomly assigned study. All patients were on anti failure therapy with Digoxin, Captopril and Furosemide. Carvedilol was started at a dosage of 3.12 mg bid and for patients who had a systolic blood pressure >100 mmHg, heart rate >60/min and no signs of low cardiac output the dosage was increased every two weeks to a maximum of 25 mg bid. Clinical signs and symptoms, systolic and diastolic echocardiographic indexes and Tissue Doppler Imaging (TDI) data were collected from each patient. FINDINGS: Eight patients received Carvedilol (Group 1) and six received placebo (Group 2). The mean age of patients in Group1 and 2 were 16±0.7 years and 17±3 years respectively. Only one patent in Group 1 tolerated increasing Carvedilol dosage to more than 6.25 mg bid. Changes in New York Heart Association (NYHA) classification, Ejection fraction, End diastolic dimension changes, TDI systolic(S), early (Ea) and late (Aa) diastolic waves were not statistically significant in these two Groups (P>0.05). Pulse Doppler E/A wave ratio of mitral valve in Group1 and Group 2 changed from 1.1±0.37 m/s to 1.8±0.40 m/s and from 1.34±0.30 m/s to 2.6±0.23m/s respectively (P=0.04). CONCLUSION: Patients with thalassemia and dilated cardiomyopathy have poor tolerance to increasing Carvedilol dosage and develop decreased systolic blood pressure during advancement of the drug dosage. Carvedilol can be effective in prevention of progression of diastolic dysfunction in these patients.

Evaluation of myocardial function using the Tei index in patients with Kawasaki disease.

Myocarditis is a well-recognized component of Kawasaki disease, with left ventricular dysfunction occurring in more than half of the patients during the acute phase of the disease. The purpose of our study was to evaluate myocardial function in these patients using the myocardial performance index, also known as the Tei index. In a prospective study, 14 patients underwent echocardiographic evaluation, first at the time of diagnosis of the disease, in its acute phase before treatment with intravenous immunoglobulin and then 2 weeks later after treatment with immunoglobulin. We assessed the Tei-index, the ejection fraction, shortening fraction, and the presence of valvar regurgitation, pericardial effusion, or coronary arterial involvement. As a control, we also assessed 22 healthy children, matched for age and sex with the study population. Of the patients, half had an increased left ventricular Tei-index in the acute phase, as compared with the data obtained after treatment, the index changing from 0.43 +/- 0.08 to 0.35 +/- 0.06 (p equal to 0.003). An increased index for the right ventricle was found in 5 patients (36%), values being 0.30 +/- 0.05 as opposed to 0.26 +/- 0.04 (p equal to 0.009). Of the patients, 5 (35.7%) also had decreased ejection fractions and proportional shortening fractions during the acute phase, confirming left ventricular dysfunction. We concluded that the Tei-index, which measures combined systolic and diastolic function, is a simple, sensitive, and accurate tool for estimating global myocardial dysfunction in patients with Kawasaki disease.

Echocardiographic finding in beta-thalassemia intermedia and major: absence of pulmonary hypertension following hydroxyurea treatment in beta-thalassemia intermedia.

OBJECTIVES: The aim of this study was to investigate the echocardigraphic finding in beta-thalassemia intermedia (TI) and beta-thalassemia major (TM) and to compare this finding together and with healthy control subjects. METHODS: Fifty TI, who have been treated with hydroxyurea (HU) for 7 yrs and 51 transfusion dependent TM were compared with 50 age and sex matched healthy control subjects. Left and right ventricular parameters, systolic and diastolic functions, stroke volume, cardiac index and indices of pulmonary hypertension (PHT) were determined by two-dimensional, M-mode echocardiography and Doppler echocardiography. RESULTS: Left ventricular parameters such as left ventricular end diastolic diameter, left ventricular end systolic diameter and also interventricular septal diameter in systole and diastole were significantly higher in TI patients compared with TM and control group (P < 0.05). There was elevated left ventricular mass (LV mass) in TI and TM patients compared with controls (P < 0.05). Regarding the LV diastolic function indices, E and A were significantly higher in TI patients compared with TM patients and control which were compatible with high output state. Measurement of pulmonary acceleration time and tricuspid and pulmonary valve continuous-wave Doppler tracing in patients with tricuspid regurgitation and pulmonary insufficiency showed no difference between TI, TM and control group. CONCLUSION: Both TI and TM patients who have no clinical signs of cardiac involvement have significant abnormalities in volume, mass and shape of the LV which may be the consequence of chronic anemia. We found the unexpected absence of PHT in TI patients who have been treated with HU. In conclusion Low dose HU treatment of TI patients may prevent the devastating complication of PHT.

Oral sildenafil to control pulmonary hypertension after congenital heart surgery.

This study investigates the role of oral sildenafil in decreasing pulmonary pressure after congenital heart surgery. Between September 2002 and September 2004, among a group of postoperative children with large septal defects, moderate to severe pulmonary hypertension [pulmonary artery (PA) to aortic (Ao) pressure ratio of 0.76 +/- 0.17] and systemic desaturation (Ao Sat = 0.89 +/- 0.11), oral sildenafil (0.3 mg x kg(-1), every 3 hours) was administered for a period of 24-48 hours (sildenafil group). These patients were compared to a group of 22 children with similar pathologies who did not receive sildenafil (control group). Postoperative PA pressure (28.61 +/- 7.80 vs 39.40 +/- 10.80 mm Hg) and PA/Ao pressure (0.28 +/- 0.08 vs 0.41 +/- 0.11) were significantly lower in the sildenafil group ( p = 0.001 and 0.001 respectively). Pulmonary hypertensive crisis was detected in 4 patients in the control group, but none in the sildenafil group ( p = 0.02). There was no significant rise in PA pressure following discontinuation of the drug (26.30 +/- 6.66 vs 28.49 +/- 10.93 mm Hg, p = 0.366). No significant complications were noticed regarding sildenafil use. Low doses of oral sildenafil appear to be effective and safe to control postoperative PA pressure in children. Absence of rebound pulmonary hypertension, availability, and low cost of the drug are considered as its major advantages.