Human Induced Pluripotent Stem Cell-Derived Microvesicles Transmit RNAs and Proteins to Recipient Mature Heart Cells Modulating Cell Fate and Behavior.

Microvesicles (MVs) are membrane-enclosed cytoplasmic fragments released by normal and activated cells that have been described as important mediators of cell-to-cell communication. Although the ability of human induced pluripotent stem cells (hiPSCs) to participate in tissue repair is being increasingly recognized, the use of hiPSC-derived MVs (hiPSC-MVs) in this regard remains unknown. Accordingly, we investigated the ability of hiPSC-MVs to transfer bioactive molecules including mRNA, microRNA (miRNA), and proteins to mature target cells such as cardiac mesenchymal stromal cells (cMSCs), and we next analyzed effects of hiPSC-MVs on fate and behavior of such target cells. The results show that hiPSC-MVs derived from integration-free hiPSCs cultured under serum-free and feeder-free conditions are rich in mRNA, miRNA, and proteins originated from parent cells; however, the levels of expression vary between donor cells and MVs. Importantly, we found that transfer of hiPSC components by hiPSC-MVs impacted on transcriptome and proteomic profiles of target cells as well as exerted proliferative and protective effects on cMSCs, and enhanced their cardiac and endothelial differentiation potential. hiPSC-MVs also transferred exogenous transcripts from genetically modified hiPSCs that opens new perspectives for future strategies to enhance MV content. We conclude that hiPSC-MVs are effective vehicles for transferring iPSC attributes to adult somatic cells, and hiPSC-MV-mediated horizontal transfer of RNAs and proteins to injured tissues may be used for therapeutic tissue repair. In this study, for the first time, we propose a new concept of use of hiPSCs as a source of safe acellular bioactive derivatives for tissue regeneration.

Arterial stiffness in adult patients after Fontan procedure.

OBJECTIVES: Increased arterial stiffness is a risk factor of atherosclerosis and cardio-vascular complications. The aim of the study was to determine whether peripheral vascular function might be an early marker of impaired health status in patients with a single ventricle after Fontan procedure. METHODS AND RESULTS: Twenty five consecutive adults (11 women and 14 men) aged 24.7 ± 6.2 years after the Fontan procedure and 25 sex, age and BMI match healthy volunteers underwent physical examination, blood analysis, transthoracic echocardiography and noninvasive assessment of aortic stiffness. Augmented pressure and Augmentation Index (AIx) were both significantly elevated in Fontan when compared to the controls (6,08 ± 0,7 vs. 2,0 ± 3,7; p = 0.002 and 17,01 ± 3,3 vs. 6,05 ± 11; p < 0.001, respectively). There were no differences in pulse wave velocity (PWV), mean blood pressure (BP), brachial pulse pressure (PP), central: systolic BP, diastolic BP and PP. In Fontan group we find negative correlation between PWV and SatO2 (r = -0.68; p = 0.04) and positive correlation with WBC (0.72; p = 0.72; p = 0.013), INR (0.81; p = 0.008), TNFα (r = 0.45; p = 0.04), and postoperative time (r = 0.77; p = 0.02). AIx correlates positively only with age at surgery (r = 0.45; p = 0.04). Bilirubin level correlates positively with brachial PP (r = 0.71; p = 0.02) and central PP (r = 0.68; p = 0.03).The multivariate model showed that SatO2 (ß = -0.44, p = 0.04) was the only independent predictor of PWV (R² = 0.32, p = 0.03). CONCLUSION: Adult Fontan patients have an increased arterial stiffness assessed by a noninvasive technique. Low arterial oxygen saturation postoperative time, age at surgery, white blood cells, TNFα and bilirubin level are associated with arterial stiffening in these patients. The combination of blood parameters of the hepatic function and noninvasive measurements of arterial stiffness could be helpful in comprehensive care of patients with Fontan circulation.

Single ventricle function and exercise tolerance in adult patients after Fontan operation.

BACKGROUND: Patients who have undergone a Fontan operation (FO) may suffer from both systolic and diastolic single ventricle (SV) dysfunction. AIM: The aim of the study was to quantify non-invasively the systolic and diastolic single ventricle function in adult FO patients and to assess its effect on exercise tolerance. METHODS: We investigated 21 patients (12F; 9M) after FO with morphological left ventricle with a mean age of 26 +/- 6 years, and 17 age-matched, healthy people (control group). Pulse-wave Doppler signals from the mitral inflow, aortic flow and tissue Doppler imaging of the mitral annulus were obtained. A cardiopulmonary exercise test (CPET) was performed. RESULTS: The Fontan patients, as compared to the controls, had a lower value of SV ejection fraction (SVEF), E velocity, E/A ratio, aortic valve velocity time integral, exercise time, SatO2, VO(2peak) and significantly higher E/E' ratio, VE/VCO(2peak) and VE/VO(2peak'). We found negative correlations between E/E' and exercise time and VO(2peak). Positive correlations were found between E/E' and VE/VCO(2peak) and age at surgery. S' velocity correlated positively with SVEF, VO(2peak) and negatively with E/E' ratio. Patients after FO with E/E' ratio > or = 12 had a significantly lower oxygen uptake when compared to those with E/E' ratio < 12. CONCLUSION: Adult patients after Fontan operations are characterized by both systolic and diastolic dysfunction of the single ventricle, associated with severe exercise intolerance reflected by shorter duration of exercise with decreased oxygen uptake and increased ventilatory response. E/E' ratio assessed by Tissue Doppler echocardiography can be a powerful predictor of oxygen uptake and ventilatory response.

[Therapeutic results in children with hypoplastic left heart syndrome after Norwood procedure]. / Wyniki leczenia dzieci z zespolem niedorozwoju lewego serca po operacji metoda Norwooda.

UNLABELLED: Hypoplastic left heart syndrome (HLHS) encompasses hypoplasia or atresia of the left ventricle, stenotic or artretic aortic and mitral valves and hypoplasia of the ascending aorta. The aim of the 1-st stage operation called the modified Norwood procedure is reconstruction of the systemic flow, providing an adequate pulmonary flow and relieving interatrial restriction. The aim of the study was the analysis of treatment results after the Norwood operation in children hospitalized at Cardiology and Cardiac Surgery Departments in the period of 2009-2012. The material consisted of 65 children (42 males, 23 females). The following factors were analyzed: the age on admission, general condition, pre-operative clinical course. RESULTS: The mean age of children on admission was 4.4 ± 4.1 days and mean body weight--3.3 ± 0.5 kg. The general condition was good in the majority of patients (74%). The remaining children were found to have early symptoms of congestive heart failure (CHF). Cardiological and/or surgical interventions were necessary in 33 (50.8%) patients, among them three children required both procedures. In the majority of patients (n = 21, 32%), the main cause of intervention was re-coarctation of the neo-aortic isth- mus treated with balloon plasty and/ or stenting. In the early post-operative period, six children died due to CHF (n = 4) and infections (n = 2), while the remaining six children died due to various complications while waiting for the 2nd stage. CONCLUSIONS: Despite the progress in diagnosis and treatment of children with HLHS the mortality is still high.

[The use of extracorporeal life support and continuous venovenous haemodiafiltration in severe angiotensin converting enzyme inhibitor, calcium channel bloker and beta-blocker multidrug intoxication]. / Zastosowanie pozaustrojowego utlenowania krwi i wspomagania krazenia oraz ciaglej zylno-zylnej hemodiafiltracji w ciezkim zatruciu inhibitorem konwertazy, blokerem kanalu Ca++ i beta-blokerem.

Extracorporeal membrane oxygenation (ECMO) is an established method of treatment for extremely severe respiratory failure (ARDS, acute respiratory distress syndrome), for mechanical circulatory support after cardiac surgery as well as advanced resuscitation technique in specific cases. Severe multidrug poisoning causing an acute cardiovascular insufficiency combines all of these indications. We report a case of multiple drug poisoning: ACE inhibitor (ACE-I), beta-blockers and calcium channel blockers. Acute heart failure and multiorgan failure, have been successfully cured with the concomitant use of ECMO, hemodiafiltration and oscillatory ventilation.

Staged treatment of a premature newborn with interrupted aortic arch and aorta-pulmonary window using intraoperative hybrid procedure before subsequent total correction - Long-term follow-up.

Interrupted aortic arch (IAA) associated with an aortopulmonary window (APW) is a rare cardiac malformation that needs an immediate diagnosis after birth and surgical treatment to avoid irreversible pulmonary lesions. Herein, we describe a case of successful staged treatment of premature neonate using many operative procedures. The first stage was stenting of patent ductus arteriosus with banding of pulmonary artery branches using a hybrid approach. At the age of one, he underwent total correction of malformation using Gore-Tex patch. Two procedures of implantation and redilatation of the previously implanted stents were performed in the following years. In the 8-year follow-up, the patient has been in good clinical condition, without cardiac symptoms. To the best of our knowledge, this is the first case report representing such a long-term follow-up of treatment of IAA accompanied by APW.

The cardioprotective and anti-inflammatory effect of inhaled nitric oxide during Fontan surgery in patients with single ventricle congenital heart defects: a prospective randomized study.

BACKGROUND: Fontan surgery with cardiopulmonary bypass (CPB) causes tremendous systemic stress and inflammatory responses, affecting postoperative organ function, morbidity, and mortality. Although this reaction triggers partially protective anti-inflammatory responses, it is harmful in patients with single ventricle congenital heart defects. Despite decades of research, an effective anti-inflammatory and stress defense strategy is lacking. This study investigated the influence of inhaled nitric oxide (NO) during CPB on early clinical results, including the duration of postoperative respiratory support as a primary outcome and a panel of laboratory analytes. METHODS: In this study, 115 patients were randomized to the Fontan-NO group (n = 48) and the Fontan group (n = 49). Eighteen patients were excluded from the study. The Fontan-NO group received NO inhaled directly into the oxygenator during CPB. Clinical data were collected, and blood samples were drawn for analysis at repeated intervals. Multiplex assays were used to analyze a proteome profile of molecules involved in stress response, inflammation, metabolic reactions, as well as heart and lung protection. RESULTS: Fontan-NO patients had significantly shorter respiratory support time with a median of 9.3 h (7.0; 13,2) vs 13.9 h (3.7; 18.5) by the absolute difference of 4.6 h [95% confidence interval, - 30.9 to 12.3; (p = 0.03)]. In addition, they have a shorter time in intensive care (p = 0.04) and lower pulmonary artery pressure after CPB discontinuation (p = 0.04), 4 h (p = 0.03) and 8 h (p = 0.03) after surgery. Fontan-NO patients also had a lower concentration of lactates (p = 0.04) and glucose after separation from CPB (p = 0.02) and lower catecholamine index (p = 0.042). Plasma factors analysis has shown a significantly higher concentration of interleukin-10, and a lower concentration of interleukin-6, interleukin-8, interleukin-1ß, pentraxin, matrix metalloproteinase-8, troponin-I, creatine kinase myocardial band (CK-MB), and insulin in Fontan-NO group. CONCLUSIONS: NO inhaled into the oxygenator during CPB can improve short-term clinical outcomes. It shortens intubation time and intensive care time. It reduces inflammatory response, improves myocardial and lung protection, and diminishes metabolic stress in patients with a single ventricle undergoing Fontan surgery. TRIAL REGISTRATION NUMBER: The trial was preregistered, supervised, and supported by The Polish National Science Center ( NCN/01/B/NZ5/04246 ).

The increase of the pulmonary blood flow inhigh-risk hypoxic patients with a bidirectional Glenn anastomosis.

BACKGROUND: An additional shunt in single ventricle patients with Glenn anastomosis may increase pulmonary flow at the expense of ventricle volume overloading. The performance of the modification depends on pulmonary resistance, indicating better results in favorable hemodynamic conditions. AIMS: The study aims at analyzing the influence of precisely adjusted pulsatile shunt in borderline high-risk Glenn patients on early and late results. METHODS: The study involved 99 patients (including 21 children) with the bidirectional Glenn and accessory pulsatile shunt (BDGS group), and 78 patients with the classic bidirectional Glenn anastomosis (BDG group). RESULTS: There was 1 death in the BDGS group and 4 deaths in the BDG group. No difference in mortality (P = 0.71) was found. The Fontan completion was achieved in 69 (88.5%) children in the BDG group and 18 (85.7%) patients in the BDGS group, without fatalities. No intergroup differences in postoperative pulmonary artery pressure (P = 0.10), ventilation time (P = 0.12), the McGoon ratio (P = 0.9), or chylothorax frequency (P = 0.14) were observed. Intensive care unit (P = 0.28) and hospitalization (P = 0.05) times were comparable. Echocardiography revealed no significant differences in the ventricle and atrioventricular valve function between groups. In the BDGS group, higher blood oxygen saturation (P = 0.03) and increase of the McGoon index (P = 0.002) were noted. CONCLUSIONS: Bidirectional Glenn anastomosis with precisely adjusted accessory pulmonary blood flow provides stable hemodynamics and adequate oxygen saturation in borderline, profoundly hypoxic patients. An advantageous pulmonary artery development before Fontan completion was observed.

Noninvasive assessment of liver status in adult patients after the Fontan procedure.

INTRODUCTION A hemodynamic derangement in Fontan circulation causes liver pathology known as Fontan­­associated liver disease. Although liver biopsy is a standard for diagnosis of liver fibrosis, noninvasive methods are being developed, including shear wave elastography (SWE). OBJECTIVES We aimed to evaluate the degree of liver stiffness (LS) using SWE in patients with Fontan circulation in a long­­term follow­­up and to investigate a relationship between patient characteristics and LS. PATIENTS AND METHODS The study included 59 patients after the Fontan procedure. Clinical examinations and laboratory tests were performed. According to the stage of LS, patients were divided into 2 subgroups: group 1 (METAVIR stages F1 and F2) and group 2 (METAVIR stages F3 and F4). The ratio of aspartate transaminase to alanine transaminase, aspartate transaminase­­to­­platelet ratio index (APRI), fibrosis­­4 (FIB­­4) score, and Forns index were assessed. RESULTS The median LS was 9.1 kPa (interquartile range, 3.9-18.5 kPa). Five patients (9%) demonstrated LS in stage F1; 14 (26%), F2; 28 (52%), F3; and 7 (13%), F4. Group 2 had significantly higher aspartate transaminase and γ­­glutamyltranspeptidase levels, APRI, FIB­­4, and Forns index, and lower platelet count than group 1. A canonical correlation analysis indicated that LS and thrombocytopenia were related to time from the Fontan procedure, age at procedure, and single ventricular ejection fraction. CONCLUSIONS We showed that adult patients after the Fontan procedure develop liver dysfunction. Time from surgery, age at procedure, and single ventricular ejection fraction are related to the degree of LS assessed by SWE. Finally, SWE, APRI, Forns index, and FIB­4 score may help assess the degree of liver fibrosis.

Pulmonary valve and right ventricular outflow tract surgery in adults: 23-year experience.

BACKGROUND: Surgery of the pulmonary valve, right ventricular outflow tract, and pulmonary artery falls under the domain of paediatric cardiac surgery. However, 97 adult patients underwent such operations in our institution from 1993 to 2016. AIM: This study aims to analyse preoperative risk factors, intraoperative data, postoperative outcomes, and long-term survival to identify the potential predictors of mortality and high-risk patients. METHODS: We divided our patient cohort into three groups in accordance with surgical indications: 17 patients with pulmonary valve endocarditis (group A), 70 patients with congenital defects involving the pulmonary valve (group B), and 10 patients who underwent pulmonary valve surgery for other indications, such as tumour or other acquired valvular disease (group C). RESULTS: Gender distribution was comparable in all the three groups, with about 40% of the total number of patients being female. The mean age was 35.9 ± 15.7 years. Sixty (61.9%) patients had a history of cardiac surgery. Various concomitant cardiac surgical procedures were necessary in 49 (50.5%) cases. There were two (11.8%) in-hospital deaths in group A, two (2.9%) in group B, and none in group C. Within the mean follow-up time of 6.6 ±7.2 years, three (17.7%) patients in group A, two (2.9%) in group B, and four (40%) in group C died. CONCLUSIONS: Adult patients with pulmonary valve disease are often previously heart-operated and often need concomitant procedures. The operative risk in patients with pulmonary valve endocarditis is high. Surgery of congenital defects of the pulmonary valve is safe and can be performed with excellent outcomes.

Coagulation abnormalities and liver function after hemi-Fontan and Fontan procedures - the importance of hemodynamics in the early postoperative period.

INTRODUCTION: The causes of coagulation abnormalities and thromboembolic complications during staged Fontan approach in patients with single ventricle remain unclear. This study was designed to evaluate the coagulation profile in the early postoperative period after hemi-Fontan and Fontan procedures with relationship to liver function and hemodynamic variables. MATERIALS AND METHODS: The prospective study on 43 patients after hemi-Fontan (group 1) and 37 patients after Fontan procedure (group 2) was carried out. Coagulation profile (factor VII, factor VIII, ATIII, fibrinogen, prothrombin), liver function (total serum protein, albumin, AST, ALT, bilirubin), and hemodynamic variables were assessed on postoperative day 1 and 5 and compared to preoperative measures. RESULTS: Factor VIII concentration was significantly higher on first postoperative day in both groups. On postoperative day 5 the concentration of factor VIII was significantly decreased in group 1 whereas constant in group 2. The concentration of factor VII, ATIII, fibrinogen, and prothrombin was significantly decreased on first and increased on fifth postoperative day after both hemi-Fontan and Fontan procedures. The increase in bilirubin concentration was more distinctive after Fontan operation (p=0.003) with lower AST in this group (p<0.0001). The single ventricle function, pO2 and central venous pressure had significant influence on factor VIII (p=0.034), factor VII (p=0.012), ATIII (p=0.006), and prothrombin (p=0.024) concentrations in group 2 with no significant influence in group 1. CONCLUSIONS: The distinctive causes of coagulation abnormalities during staged Fontan approach are hemodynamic changes and temporary liver dysfunction. Elevated concentration of factor VIII and significant influence of hemodynamics on coagulation profile could contribute to postoperative thromboembolic complications.

Diverse impact of xeno-free conditions on biological and regenerative properties of hUC-MSCs and their extracellular vesicles.

Growing evidence indicates that intracellular signaling mediated by extracellular vesicles (EVs) released by stem cells plays a considerable role in triggering the regenerative program upon transplantation. EVs from umbilical cord mesenchymal stem cells (UC-MSC-EVs) have been shown to enhance tissue repair in animal models. However, translating such results into clinical practice requires optimized EV collection procedures devoid of animal-originating agents. Thus, in this study, we analyzed the influence of xeno-free expansion media on biological properties of UC-MSCs and UC-MSC-EVs for future applications in cardiac repair in humans. Our results show that proliferation, differentiation, phenotype stability, and cytokine secretion by UC-MSCs vary depending on the type of xeno-free media. Importantly, we found distinct molecular and functional properties of xeno-free UC-MSC-EVs including enhanced cardiomyogenic and angiogenic potential impacting on target cells, which may be explained by elevated concentration of several pro-cardiogenic and pro-angiogenic microRNA (miRNAs) present in the EVs. Our data also suggest predominantly low immunogenic capacity of certain xeno-free UC-MSC-EVs reflected by their inhibitory effect on proliferation of immune cells in vitro. Summarizing, conscious selection of cell culture conditions is required to harvest UC-MSC-EVs with the optimal desired properties including enhanced cardiac and angiogenic capacity, suitable for tissue regeneration. KEY MESSAGE: Type of xeno-free media influences biological properties of UC-MSCs in vitro. Certain xeno-free media promote proliferation and differentiation ability of UC-MSCs. EVs collected from xeno-free cultures of UC-MSCs are biologically active. Xeno-free UC-MSC-EVs enhance cardiac and angiogenic potential of target cells. Type of xeno-free media determines immunomodulatory effects mediated by UC-MSC-EVs.

Neonatal repair of tetralogy of Fallot results in improved pulmonary artery development without increased need for reintervention.

OBJECTIVE: Despite a continuous improvement in operative outcome the optimal timing for the repair of tetralogy of Fallot (TOF) remains controversial. The purpose of this study was to evaluate the results following neonatal repair of TOF and the need for reintervention associated with this strategy. METHODS: Retrospective review of 66 consecutive patients with TOF and confluent pulmonary arteries, who underwent repair immediately after diagnosis. Group I (n=46) had a median age of 5 days (1-29) and Group II (n=20) had a median age of 56 days (32-270). A transventricular approach was used in all cases, and 58/66 (88%) patients received a transannular patch. The median follow-up interval was 35 months (1-79). RESULTS: There were three early deaths (4.5%) and no late deaths for an actuarial survival rate of 95.4% at 1 and 5 years. Univariate analysis of patient and procedural variables demonstrated that early mortality was only influenced by associated non-cardiac conditions (P=0.04). At median interval of 9.8 months (3-41), 12 patients required additional intervention. During the follow-up period, a significant increase in Nakata index was observed only among neonates. Freedom from reintervention at 1 month, 1 and 5 years was: 100, 84.2 and 81% in group I and 100, 84, 78.9% in group II. Surgical weight below 2.5 kg (P<0.001), low arterial saturation in the early postoperative period (P=0.04) and small preoperative branch pulmonary artery size (<0.01) were associated with need for reintervention during follow-up. CONCLUSIONS: Elective repair of TOF in neonates with confluent central pulmonary arteries has excellent results in the absence of significant associated non-cardiac conditions. While enhancing the development and growth of the pulmonary arteries, neonatal repair affords a freedom from reintervention no different from patients repaired during infancy. Preoperative weight < 2.5 kg and small left pulmonary artery size are associated with higher incidence reintervention during follow-up.

Right ventricle-to-pulmonary artery shunt and modified Blalock-Taussig shunt in preparation to hemi-Fontan procedure in children with hypoplastic left heart syndrome.

OBJECTIVE: The advantageous effect of right ventricle-to-pulmonary artery shunt (RV-PA) on the early postoperative hemodynamics in the Norwood procedure for hypoplastic left heart syndrome (HLHS) is well known. Numerous controversies still exist with respect to the late consequences of this new palliation method in preparation for the second stage procedure. METHODS: Between September 1997 and September 2004, a consecutive series of 78 children with HLHS from a single institution underwent the hemi-Fontan procedure: Group 1 (n=27) after Blalock-Taussig shunt (BT), and Group 2 (n=51) after RV-PA. Hemodynamic, echocardiographic and clinical perioperative data were analyzed. RESULTS: There were no significant differences in the age and operative weight (Group 1: 6.9+/-1.04 months, 6.22+/-0.99 kg; Group 2: 6.57+/-1.12 months, 6.36+/-0.86 kg). Children after RV-PA were characterized by a significantly higher preoperative hematocrit value (P=0.014), lower aortic and superior vena cava oxygen blood saturation (P<0.001, P=0.024), severe right ventricle hypertrophy more rarely diagnosed in echocardiography (P<0.004), lower Qp:Qs ratio (P=0.011), larger right (P=0.001) and left (P=0.006) pulmonary artery index and a shorter intensive care unit stay after the hemi-Fontan procedure (P=0.004). CONCLUSIONS: The Norwood procedure with the RV-PA shunt provides satisfactory late hemodynamics and improves the development of the pulmonary arteries. Children with hypoplastic left heart syndrome subjected to this new method of palliation are good candidates for the hemi-Fontan procedure.

Three-dimensional visualization of connexin 43 on the human cardiomyocytes.

Gap junctions created by a family of connexin proteins play an important role in the development of human heart. It has been previously shown that the abnormalities of right ventricular outflow tract are related to an altered level of expression of connexin 43. The right ventricular outflow tract narrowing, stenosis, or atresia of the main pulmonary artery and hypertrophy of the right ventricle are observed in tetralogy of Fallot. The aim of the current study was to determine the distribution of connexin 43 on the surface of human cardiomyocytes obtained during reparative surgery for tetralogy of Fallot. Connexin 43 distribution in these cells was compared with distribution of connexin 43 in cardiomyocytes obtained from patients without right ventricular outflow tract pathology. Cardiomyocytes isolated from tissue biopsy were cultured on collagen substratum, fixed with paraformaldehyde, and incubated with goat antihuman connexin 43 antibodies and secondary donkey antigoat antibodies conjugated with fluorescent indocarbocyanine. Z-series of optical sections were recorded using a laser scanning confocal microscope. Three-dimensional data stacks were visualized using volume-rendering techniques. Images of connexin 43 fluorescence revealed a pattern of three-dimensional distribution of connexin on the surface of an individual cardiomyocyte. Cardiomyocytes from tetralogy of Fallot and hearts with normal right ventricular outflow tract differ in the organization of connexin 43. Cardiomyocytes from tetralogy of Fallot hearts revealed disturbed distribution of connexin 43. The protein is located irregularly on the entire surface of the cell. In the controls, connexin 43 can be visualized within the intercalated disks only. These disturbances may influence heart maturation, cause hypertrophy of the right ventricle, and induce severe arrhythmias in children with tetralogy of Fallot.

Right ventricle-to-pulmonary artery shunt versus modified Blalock-Taussig shunt in the Norwood procedure for hypoplastic left heart syndrome - influence on early and late haemodynamic status.

OBJECTIVE: The aim of this study was to assess changes in early and late haemodynamic status after the Norwood procedure (NP), caused by the implementation of right ventricle-to-pulmonary artery shunt (RV-PA). METHODS: A consecutive series of 68 children with hypoplastic left heart syndrome underwent NP: Group 1 (n=31) with the application of a modified Blalock-Taussig shunt and Group 2 (n=37) with RV-PA. Haemodynamic data from the early postoperative period (72 h after the operation) and cardiac catheterisation data, as well as blood tests before the hemi-Fontan procedure (HF) were analysed. Univariate (chi(2) test, Mann-Whitney's and Student's t-tests) and multiple regression analysis were carried out. RESULTS: In Group 1, circulatory collapse requiring resuscitation occurred in 15 (48.4%) children, within 72 h after the procedure. The resuscitation was unsuccessful in nine (29%) cases. The operative mortality (30 days) was 35%. In Group 2, two (5%) children died within the early and two (5%) within the late postoperative period. The postoperative course in the remaining children from Group 2 was uneventful. In Group 2 there was a significantly higher mean diastolic pressure after NP (P<0.05). The arterial pulse pressure after NP was significantly lower in Group 2 (P<0.05). Before HF, the application of RV-PA was associated with a lower Qp:Qs ratio (P=0.020), lower aortic pulse pressure (P=0.004) and lower aortic oxygen saturation (P=0.039). CONCLUSIONS: A stable haemodynamic status due to independent coronary perfusion, higher diastolic and lower pulse pressure is the most advantageous effect of RV-PA, resulting in a lower mortality and morbidity after NP. A lower Qp:Qs ratio eliminates the danger of the ventricular volume overload and ensures good conditions for the development of the pulmonary circulation before HF.

The operative outcome in children with supravalvular aortic stenosis.

The authors present their experience in surgical treatment of children with supravalvular aortic stenosis (SAS). A retrospective analysis was carried out on 20 patients operated in the years 1980-1999. The group included 12 boys and 8 girls aged 0.9 to 14.5 years (mean 7.8 +/- 3.4 years). The diagnosis of Williams syndrome in 6 children (30%) was based on the typical face. The mean systolic pressure gradient across the SAS was 84.3 +/- 34.5 mmHg (range from 41 to 168 mmHg). Intraoperative studies allowed to determine that 16 (80%) children had the hourglass type, 2 (10%) tubular type and 2 (10%)--fibromuscular membrane type of stenosis. Sixteen (80%) children had anomalies of the aortic valve and/or coronary arteries, and in 13 (56%) children associated heart or great vessels anomalies were noted. All the patients were operated on using cardiopulmonary bypass and hypothermia. The associated anomalies were corrected simultaneously. There were no early and late deaths. Because of restenosis one child was reoperated. In the follow up the mean systolic pressure gradient between the left ventricle and ascending aorta revealed by echocardiography in 19 (95%) children to be 8 +/- 2 mmHg (range from 0 to 28 mmHg). Eighteen children are now in NYHA class I (New York Heart Association) and develop normally. Supravalvular aortic stenosis is a rare complex anomaly, which, because of life-threatening complications and low operative risk, should be fully repaired as soon as possible.