Jacek Kołcz

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-Whitneys and Students 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.

Extracorporeal life support in severe propranolol and verapamil intoxication.

Combined poisoning with calcium-channel blockers and β-blockers is usually associated with severe heart failure. This report shows the effectiveness of emergency extracorporeal life support in treating life-threatening simultaneous propranolol and verapamil intoxication. A 15-year-old girl presented in cardiogenic shock after alcohol consumption and a propranolol and verapamil overdose; plasma concentrations: propranolol, 0.53 m/mL; verapamil, 1.06 mg/mL. She was successfully resuscitated with extracorporeal life support. Therapeutic plasma exchange was initiated. Extracorporeal support was discontinued 70 hours later. The patient made a full recovery. Simultaneous verapamil and propranolol overdoses can cause severe hemodynamic compromise and arrest of electrical and mechanical function of the heart. Emergency extracorporeal life support can successfully maintain vital organ blood flow and allows time for drug metabolism, redistribution, and removal. Therapeutic plasma exchange may reduce the time of emergency extracorporeal life support. Emergency extracorporeal life support should be considered early in cases of near-fatal intoxications with cardiodepressive drugs.

Factors influencing early outcome of Norwood procedure for hypoplastic left heart syndrome

OBJECTIVE [corrected] The operative outcome of the Norwood procedure for hypoplastic left heart syndrome is still not satisfactory. Conflicting reports concern factors associated with early Norwood procedure mortality and the reasons for the instability after surgery are not sufficiently understood. The purpose of this study was to determine some perioperative factors influencing early (30 days) outcome. METHODS We retrospectively analyzed a group of 30 consecutive children with hypoplastic left heart syndrome (aged 5-39 days) who underwent Norwood procedure in 1997 and 1998. The following factors were considered and statistically analyzed: operative age, birth weight, operative weight, serum level of bilirubin, aminotransferases, creatinine, urea, arterial blood gasses, anatomic subgroups, ascending aorta and arch size, systemic to pulmonary modified right Blalock-Taussig shunt size, cardiopulmonary circulatory arrest time, cardiopulmonary bypass time, and delayed chest closure. Eighteen patients underwent hemi-Fontan procedure with one late death and the modified Fontan operation was performed in 16 of them (one late death). RESULTS The early mortality was 37%. Seven deaths (64%) occurred during the first 24 h after operation. There was a significant difference between survivals and non-survivals in: birth weight (P=0.047), operative age (P=0.016), preoperative serum level of bilirubin (P=0.044), and cardiopulmonary circulatory arrest time (P=0.006). The other assessed factors were not found to be predictors of early mortality. All 16 survivals followed up are in New York Heart Association class I or II. CONCLUSIONS Anatomic and functional status of the patient, as well as procedural factors are related to Norwood operation early mortality. High mortality in hypoplastic left heart syndrome after stage I surgery indicates the necessity of assessing all factors which may determine further improvement in the outcome.

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. Stem Cells 2015;33:2748–2761

Hypoplastic left heart syndrome with an anomalous origin of the left coronary artery.

Abnormal origin of the coronary artery in children with hypoplastic left heart syndrome is an extremely rare defect. We describe a newborn with concomitant hypoplastic left heart syndrome and abnormal origin of the left coronary artery arising from the right pulmonary artery. A Norwood procedure and direct reimplantation of the left coronary artery to the ascending aorta was performed.

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 messageType 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.

Iron deficiency and hematological changes in adult patients after Fontan operation

BACKGROUND Growing evidence indicates that iron-deficiency anemia is common in patients with congenital heart diseases. The aim of this study was to characterize hematologic changes and iron metabolism in adult Fontan patients. We also searched for the associations between these parameters and physical performance in the study group. METHODS AND RESULTS Thirty-two white Fontan patients with a mean age of 25 ± 4.5 years and 30 healthy control subjects matched for age and sex were studied. Complete blood count together with iron-related parameters was determined in plasma of peripheral venous blood. The cardiopulmonary exercise test was performed. The Fontan patients had higher red blood cell counts (6.0 ± 2.1 × 10(9)/μl vs. 4.8 ± 0.4 × 10(9)/μl, p<0.001), hemoglobin (16.7 ± 1.4 g/dl vs. 14.2 ± 1.3g/dl, p<0.001), hematocrit (49 ± 3.4% vs. 42.1 ± 3.1%, p<0.001), red cell distribution width (RDW) (14.3 ± 2.4% vs. 12.8 ± 0.5%, p<0.001), while mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were similar in both the groups. Compared to the controls, the Fontan patients had higher unsaturated iron binding capacity (46.1 ± 12.6 μmol/l vs. 38.4 ± 11.9 μmol/l, p=0.02), total iron-binding capacity (62.8 ± 9.8 μmol/l vs. 57.8 ± 8.5 μmol/l, p=0.04), lower transferrin saturation (27.4 ± 11.4% vs. 34.6 ± 13.4%, p=0.03), and oxygen uptake, while iron and ferritin levels were comparable in both the groups. The multivariate model showed that SatO2 and cystatin C were independent predictors of RDW, and alanine aminotransferase was an independent predictor of ferritin level. Interestingly RDW was an independent predictor of oxygen uptake. CONCLUSION Adult patients after Fontan operation despite having increased hemoglobin, hematocrit, and red blood cells have insufficient iron stores. Red cell distribution width is an indicator of iron deficiency in adult Fontan patients and it correlates with lower exercise capacity. Elevated ferritin levels in adult patients after Fontan surgery are associated with liver failure.

Impact of right ventricle–pulmonary artery conduit placement on pulmonary artery development after the Norwood procedure in hypoplastic left heart syndrome

OBJECTIVES The right ventricle-to-pulmonary artery (RV-PA) shunt in the Norwood procedure (NP) for children with hypoplastic left heart syndrome (HLHS) provides stable haemodynamics and improves interstage survival. The aim of the study was to find the effect of RV-PA placement on pulmonary artery development after the NP. METHODS A prospective, randomized study of 60 children with HLHS was carried out between 2008 and 2010. All children underwent the NP in the neonatal period and survivors underwent the hemi-Fontan operation (at a mean age of 4.78 ± 2.8 months). RV-PA was left side to the neo-aorta in 32 children (the first group) and right side to the neo-aorta in 28 children (the second group). Echocardiography and angiograms were used to asses the pulmonary artery size. RESULTS There was a significant difference between right pulmonary artery (RPA) and left pulmonary artery (LPA) diameters in both groups before the NP (first: 4.94 ± 0.27 vs. 4.26 ± 0.22, P = 0.04; second: 4.97 ± 0.23 vs. 4.14 ± 0.17, P = 0.003). This difference was not significant when z-scores were taken into account. The dynamics of the pulmonary artery development was similar in both groups comparing pre-Norwood and pre-hemi-Fontan periods. A slight increase in the LPA and the RPA diameter with a significant decrease in the z-scores was noted. At the pre-hemi-Fontan stage, there was no significant difference in the diameter and the z-score between LPA and RPA in the second group, whereas in the first group, the z-score for LPA was significantly lower compared with RPA (-1.34 ± 1.6 vs. -0.86 ± 1.4, P = 0.016). CONCLUSIONS Placement of the RV-PA conduit on the right side to the neo-aorta ensures more equal distribution of the blood to the pulmonary arteries and better development of the LPA.

Outcomes following non-valved autologous reconstruction of the right ventricular outflow tract in neonates and infants.

OBJECTIVE Controversy surrounds the optimal method of establishing right ventricle to pulmonary artery continuity in neonates and infants with congenital heart disease. We reviewed our experience with non-valved autologous reconstruction of the right ventricular outflow tract to determine mid-term outcome and risk factors for reintervention. METHODS Between 1998 and 2006, 34 consecutive patients underwent non-valved autologous right ventricular outflow tract reconstruction. The need for postoperative catheter-based intervention or reoperation was assessed using relevant patient and procedure-related variables. RESULTS Diagnoses included tetralogy of Fallot with anomalous coronary (n=3), tetralogy of Fallot with pulmonary atresia (n=10), truncus arteriosus communis (n=15), and other (n=6). Median age at surgery was 5 days (1-270 days). Twenty-six (76%) patients were neonates. Median weight was 3.1kg (1.8-7.3kg). At a median follow-up of 43 months (1-90 months), 15 (50%) patients underwent reoperation and 7 (23%) underwent catheter-based intervention, with a total of 16 (53%) undergoing either reoperation or catheter-based intervention. Kaplan-Meier freedom from reintervention at 6 months, 1 year, 3 years, and 5 years was 67%, 47%, 47%, and 35% for truncus arteriosus versus 87%, 82%, 68%, and 65% for diagnoses other than truncus arteriosus (p=0.05). CONCLUSIONS Mid-term outcome following non-valved autologous reconstruction of the right ventricular outflow tract is satisfactory and constitutes a sound alternative to the use of small-diameter conduits in neonates and infants. In our hands, this strategy favors certain anatomic subtypes. Non-truncus patients have significantly lower rates of reintervention. Technical details associated with the anatomical reconstruction of the posterior autologous pathway may play an important role in outcomes.

Hard choices for high-risk patients with critical left ventricular outflow obstruction: contemporary comparison of hybrid versus surgical strategy.

Surgical management of high-risk newborns with critical left ventricular outflow tract obstruction (LVOTO) involves difficult decision making and complex procedures associated with significant morbidity and mortality. We sought to compare the outcomes of the hybrid and surgical strategies for the management of neonates with critical LVOTO considered at high risk in a contemporary nonrandomized cohort. This is a retrospective review of all patients undergoing management of critical LVOTO between January 2001 and December 2008. High-risk conditions included prematurity, low birth weight, and genetic or associated cardiac and noncardiac pathology. Analysis was performed based on intention to treat. Primary and secondary outcomes were operative and 6-month mortality. The cohort included 55 patients (21 hybrid and 34 surgical [31 Norwood, 3 biventricular repair]). The cohort had a median age of 4 (range, 1-62) days, mean weight of 2.7 ± 0.5 kg, and Aristotle comprehensive score of 18.6 ± 2.9. Low birth weight (P = .0007), prematurity (P = .004), and organ dysfunction (P = .04) were risk factors for operative death. Six-month mortality was associated with need for reintervention (P = .017) in the surgical group and history of organ dysfunction (P = .02) or aortic atresia (P = .03) in the hybrid group. Logistic regression identified low birth weight (P = .05; odds ratio [OR], 5.6 [0.9-34.6]), organ dysfunction (P = .05; OR, 4.7 [0.9-22.5]), and non–hypoplastic left heart syndrome (HLHS) diagnosis (P = .03; OR, 0.06 [0.005-0.93]) as predictors of mortality for the entire cohort. No differences in operative and 6-month mortality were detected between management strategies. Although initial surgical insult is lessened by the hybrid palliation, important interstage mortality and ongoing morbidity result in similar 6-month survival with either strategy. Patient-related factors have a larger influence on outcome than the management strategy chosen.