Risk factors associated with in-hospital mortality for patients with ECLS due to postcardiotomy cardiogenic shock after isolated coronary surgery.

OBJECTIVES: Extracorporeal membrane oxygenation or extracorporeal life support (ECLS) in patients after cardiac surgery and postcardiotomy cardiogenic shock (PCS) is known to be associated with high mortality. Especially in patients after coronary artery bypass grafting (CABG) and PCS, ECLS is frequently established. The aim of this analysis was to evaluate factors associated with in-hospital mortality in patients treated with ECLS due to PCS after CABG. METHODS: Between August 2006 and January 2017, 92 consecutive patients with V-A ECLS due to PCS after isolated CABG were identified and included in this retrospective analysis. Patients were divided into survivors (S) and non-survivors (NS) and analyzed with risk factors of in-hospital mortality. RESULTS: In-hospital mortality added up to 61 patients (66%). Non-survivors were significantly older (60 ± 812 (S) vs. 67 ± 10 (NS); p = 0.013). Bilateral internal mammary artery graft was significantly more frequently used in S (23% (S) vs. 2% (NS); p = 0.001). After 24 h of ECLS support, median lactate levels were significantly higher in NS (1.9 (1.3; 3.5) mmol/L (S) vs. 3.5 (2.1; 6.3) mmol/L (NS); p = 0.001). NS suffered more often acute kidney injury requiring dialysis (42% (S) vs. 74% (NS); p = 0.002). CONCLUSION: Mortality in patients with refractory PCS after CABG and consecutive ECLS support remains high. Failing end-organ recovery under ECLS despite optimized concomitant medical therapy is an indicator of adverse outcomes in this specific patient cohort. Moreover, total-arterial revascularization might be beneficial for cardiac recovery in patients suffering PCS after CABG and following ECLS.

Patients with Pulmonary Metastases from Head and Neck Cancer Benefit from Pulmonary Metastasectomy, A Systematic Review.

Background and Objectives: The incidence of distant metastases in patients with head and neck cancer (HNC) is approximately 10%. Pulmonary metastases are the most frequent distant location, with an incidence of 70-85%. The standard treatment options are chemo-, immuno- and radiotherapy. Despite a benefit for long-term survival for patients with isolated pulmonary metastases, pulmonary metastasectomy (PM) is not the treatment of choice. Furthermore, many otorhinolaryngologists are not sufficiently familiar with the concept of PM. This work reviews the recent studies of pulmonary metastatic HNC and the results after pulmonary metastasectomy. Materials and Methods: PubMed, Medline, Embase, and the Cochrane library were checked for the case series' of patients undergoing metastasectomy with pulmonary metastases published since 1 January 2000. Results: We included the data of 15 studies of patients undergoing PM. The 5-year survival rates varied from 21% to 59%, with median survival from 10 to 77 months after PM. We could not identify one specific prognostic factor for long-term survival after surgery. However, at least most studies stated that PM should be planned if a complete (R0) resection is possible. Conclusions: PM showed reliable results and is supposedly the treatment of choice for patients with isolated pulmonary metastases. Patients not suitable for surgery may benefit from other non-surgical therapy. Every HNC patient with pulmonary metastases should be discussed in the multidisciplinary tumor board to optimize the therapy and the outcome.

Impact of Lactate Clearance on Early Outcomes in Pediatric ECMO Patients.

Background and Objectives: Pediatric extracorporeal membrane oxygenation (ECMO) support is often the ultimate therapy for neonatal and pediatric patients with congenital heart defects after cardiac surgery. The impact of lactate clearance in pediatric patients during ECMO therapy on outcomes has been analyzed. Materials andMethods: We retrospectively analyzed data from 41 pediatric vaECMO patients between January 2006 and December 2016. Blood lactate and lactate clearance have been recorded prior to ECMO implantation and 3, 6, 9 and 12 h after ECMO start. Receiver operating characteristic (ROC) analysis was used to identify cut-off levels for lactate clearance. Results: Lactate levels prior to ECMO therapy (9.8 mmol/L vs. 13.5 mmol/L; p = 0.07) and peak lactate levels during ECMO support (10.4 mmol/L vs. 14.7 mmol/L; p = 0.07) were similar between survivors and nonsurvivors. Areas under the curve (AUC) of lactate clearance at 3, 9 h and 12 h after ECMO start were significantly predictive for mortality (p = 0.017, p = 0.049 and p = 0.006, respectively). Cut-off values of lactate clearance were 3.8%, 51% and 56%. Duration of ECMO support and respiratory ventilation was significantly longer in survivors than in nonsurvivors (p = 0.01 and p < 0.001, respectively). Conclusions: Dynamic recording of lactate clearance after ECMO start is a valuable tool to assess outcomes and effectiveness of ECMO application. Poor lactate clearance during ECMO therapy in pediatric patients is a significant marker for higher mortality.

Early and long-term outcomes comparing neonates, infants, and preadolescents requiring extracorporeal membrane oxygenation for heart failure.

BACKGROUND: Application of extracorporeal membrane oxygenation in pediatric patients with severe heart failure steadily increases. Differentiation of outcomes and survival of diverse pediatric groups is of interest for adequate therapy. METHODS: Between January 2008 and December 2016, a total of 39 pediatric patients needed veno-arterial extracorporeal membrane oxygenation support in our department. Patients were retrospectively divided into three groups: neonates (<30 days), infants (>30 days/<1 year), and toddlers/preadolescents (>1 year). Early outcomes as well as mid- and long-term survival up to 7-year follow-up were analyzed. RESULTS: Basic demographics significantly differed in terms of age, height, and weight among the groups in accordance with the intended group categorization (p < 0.05). Survival after 30 days of extracorporeal membrane oxygenation application was equally distributed among the groups, and 44% of all patients survived. In terms of survival to discharge, no significant differences were found among groups. In total, 28% of patients survived up to 7 years. Infants were significantly more likely to undergo elective surgery (p < 0.001) and were predominantly weaned off extracorporeal membrane oxygenation, whereas need for urgent surgery (p < 0.001) was significantly higher in neonate group in comparison to other groups. Multinominal logistic regression analysis revealed significantly higher odds for need for re-exposure in infant group in comparison to toddler/preadolescent group as well as for incidence of neurological impairment of toddler/preadolescent group in comparison to neonate group (odds ratio = 14.67, p = 0.009 and odds ratio = 34.67, p = 0.004, respectively). Kaplan-Meier survival estimation analysis revealed no significant differences in terms of mid- and long-term survival among the groups (Breslow p = 0.198 and log-rank p = 0.213, respectively). CONCLUSION: Veno-arterial extracorporeal membrane oxygenation is a lifesaving therapeutic chance for pediatric patients in the setting of either failure to wean from cardiopulmonary bypass or failed resuscitation from cardiac arrest. A fair part of patients could be saved by using this technology. Survival rate among the groups was similar.

Pediatric patients requiring extracorporeal membrane oxygenation in heart failure: 30-day outcomes; mid- and long-term survival. A single center experience.

Nowadays, an increasing number of neonatal and pediatric patients with severe heart failure benefits from extracorporeal membrane oxygenation (ECMO) support. A total of 39 pediatric patients needed venoarterial ECMO (vaECMO) support in our department between January 2008 and December 2016. Patients were retrospectively divided in two groups: 30-day survivor group (17 patients) and 30-day nonsurvivor group (22 patients). Outcome and factors predictive for 30-day mortality and mid- as well as long-term survival up to 7-year follow-up were analyzed by univariate analysis and Kaplan-Meier survival estimation. Basic demographics and preoperative characteristics did not differ between groups (P > 0.05). 67% of patients were successfully weaned off ECMO and 44% survived 30-day after ECMO application. After 7-year follow-up 28% of pediatric patients were alive. Thirty-day survivors were significantly more likely to undergo elective cardiac surgery (P = 0.001), whereas significantly more 30-day nonsurvivors underwent urgent surgery (P = 0.004). Odds of incidence of catecholamine refractory circulatory failure, failed myocardial recovery, and cerebral edema was significantly higher in 30-day nonsurvivor group (41.6-fold, 16-fold, and 2.5-fold, respectively). Kaplan-Meier survival estimation analysis revealed significant differences in terms of mid- and long-term survival among neonates, infants, toddlers, and preadolescents (Breslow P = 0.037 and Log-Rank P = 0.028, respectively). vaECMO provides an efficient therapy option for life-threatening heart disorders in neonates and pediatric patients being at high risk for myocardial failure leading to circulatory arrest. Urgency of surgery effected on higher mortality, but there was no difference in terms of mortality in 30-day survivor group in comparison to 30-day nonsurvivor group among neonates, infants, toddlers, and preadolescents.

Successful biventricular cardiac resynchronization therapy in a failing Fontan patient: Implications of ventriculo-ventricular interdependency in single ventricle physiology.

We describe a Fontan patient with severe heart failure who was successfully treated with biventricular cardiac resynchronization therapy (CRT). Our case shows that strain imaging might play a crucial role in guiding placement of pacing leads and in characterizing the electromechanical substrate associated with a favorable CRT response. Furthermore, we demonstrate for the first time that ventriculo-ventricular interdependency seems an important mechanical concept, which can be utilized to augment cardiac performance in failing Fontan patients with a functional hypoplastic ventricle.

Stent therapy for acute and chronic obstructions in extracardiac Fontan conduits.

We describe transcatheter therapy for early onset occlusion or stenoses of extracardiac conduits in three children who had undergone Fontan completion. Successful stent implantation was associated with complete resolution of symptoms.

Indications for and outcomes of interstage catheter interventions following the Norwood procedure: A single-institution study.

Aims: The aim of this study was to document the incidence, types, and outcome of interstage catheter interventions following the Norwood surgical palliation. Patients and Methods: A retrospective single-center study of all patients surviving the Norwood operation was performed. All data concerning interstage catheter interventions up to the completion of the superior cavopulmonary shunt were collected. Results: Catheter interventions were performed in 62 of 94 patients (66%; 38 males). These included interventions on the aortic arch (n = 44), the branch pulmonary arteries (PAs) (n = 17), and the Sano shunt (n = 14). Multiple interventions and repeat interventions were common. The minimum aortic arch diameter (pre- versus posttreatment) increased from median 3.1 (2.3-3.3) mm to 5.1 (4.2-6.2) mm (P < 0.001). The catheter pullback gradient decreased from 40 (36-46) mmHg to 9 (5-10) mmHg (P < 0.001), and the echocardiographic gradient from 54 (45-64) mmHg to 12 (10-16) mmHg (P < 0.001). The branch PA diameters increased from 2.4 (2.1-3.0) mmHg to 4.7 (4.2-5.1) mmHg (P < 0.001). The minimum Sano shunt diameters increased from 2.0 (1.5-2.1) mm to 5.9 (5.8-6.0) mm (P < 0.001); this was associated with an improvement in systemic saturation from 63% (60%-65%) to 80% (79-82%) (P < 0.001). Unexpected interstage death at home occurred in two patients who had received no interventions. The remainder received a superior cavopulmonary shunt palliation. Conclusions: Catheter interventions were common. Systematic follow-up and a low threshold for reintervention are essential to the success of staged surgical palliation for this patient cohort.

The impact of thymectomy in subgroups of Myasthenia gravis patients: a single center longitudinal observation.

BACKGROUND: Myasthenia gravis (MG) is a rare neuromuscular disorder. Symptoms can range from ptosis only to life threatening myasthenic crisis. Thymectomy is recommended for anti-acetylcholine receptor-antibody positive patients with early-onset MG. Here, we investigated prognostic factors shaping therapeutic outcomes of thymectomy to improve patient stratification. METHODS: We retrospectively collected single-center data from a specialized center for MG from all consecutive adult patients that underwent thymectomy from 01/2012 to 12/2020. We selected patients with thymoma-associated and non-thymomatous MG for further investigations. We analyzed the patient collective regarding perioperative parameters in relation to the surgical approach. Furthermore, we investigated the dynamics of the anti-acetylcholine receptor-antibody titers and concurrent immunosuppressive therapies, as well as the therapeutic outcomes in dependence of clinical classifications. RESULTS: Of 137 patients 94 were included for further analysis. We used a minimally invasive approach in 73 patients, whereas 21 patients underwent sternotomy. A total of 45 patients were classified as early-onset MG (EOMG), 28 as late-onset MG (LOMG) and 21 as thymoma-associated MG (TAMG). The groups differed in terms of age at diagnosis (EOMG: 31.1 ± 12.2 years; LOMG: 59.8 ± 13.7 years; TAMG: 58.6 ± 16.7 years; p < 0.001). Patients with EOMG and TAMG were more often female than patients in the LOMG group (EOMG: 75.6%; LOMG: 42.9%; TAMG: 61.9%; p = 0.018). There were no significant differences in outcome scores (quantitative MG; MG activities of daily living; MG Quality of Live) with a median follow-up of 46 months. However, Complete Stable Remission was achieved significantly more frequently in the EOMG group than in the other two groups (p = 0.031). At the same time, symptoms seem to improve similarly in all three groups (p = 0.25). CONCLUSION: Our study confirms the benefit of thymectomy in the therapy of MG. Both, the concentration of acetylcholine receptor antibodies and the necessary dosage of cortisone therapy show a continuous regression after thymectomy in the overall cohort. Beyond EOMG, groups of LOMG and thymomatous MG responded to thymectomy as well, but therapy success was less pronounced and delayed compared to the EOMG subgroup. Thymectomy is a mainstay of MG therapy to be considered in all subgroups of MG patients investigated.

Coarctation of the aorta and vein of Galen malformation - treatment considerations in a severely compromised patient.

A vein of Galen malformation - a rare cause of cardiac insufficiency in neonates - is sometimes associated with coarctation of the aorta, two diseases requiring urgent therapy in the neonatal period. We report on a term neonate in whom we first palliated the coarctation by stent implantation, providing time to treat the vein of Galen malformation by endovascular embolisation. Following this, the coarctation was surgically repaired and the stent was explanted.

Hemangiosis carcinomatosa as an independent risk factor for long-term survival in Non-Small Cell Lung Cancer patients.

OBJECTIVES: Recent studies have shown that blood vessel invasion (V1) influences the long-term survival of patients with Non-Small Cell Lung Cancer (NSCLC). The aim of the present study was to emphasize V1 as an independent risk factor. We evaluated the effects of V1 on the survival of NSCLC patients with UICC stages I, II, and III after surgery. METHODS: This retrospective study includes 747 consecutive patients with NSCLC who underwent anatomic resection and radical lymphadenectomy at our institution between January 2012 and December 2020. V1- were compared to V0-patients (no blood vessel invasion). All patients received adjuvant therapy according to European guidelines when indicated. After excluding patients with detection of lymphangiosis carcinomatosa, tumor-cells at the resection margin, distant metastases and those, that received neoadjuvant therapy, 1-, 3- and 5- year survival rates were assessed by Kaplan-Meier method. To proof V1 as an independent risk factor, a propensity score matched (PSM) analysis was performed regarding age, gender, UICC-stage, lymph-node involvement, and comorbidities. RESULTS: A total of 461 patients (V0: 440; V1: 21) were included in this analysis. Baseline characteristics did not show any significant difference. Mean age in V0-group was 65.7 ± 10.5 years and 64.1 ± 8.6 years in V1-group (p-value = 0.5). In the V0-group 54.8% were male, whereas in the V1-group this number was 66.7% (p-value = 0.37). Mean survival in V1-group was significantly shorter compared to V0-group (V1: 45.8 ± 9.3 months; V0: 81.1 ± 1.1 months; p-value<0.001). This was confirmed after applying a propensity score matched analysis (V0: 99.9 ± 4.9 months; V1: 45.8 ± 9.3 months; p-value<0.001) - V1 is a prognostic marker independent of UICC stage. The 1-, 3- and 5-year survival rates were significantly shorter for V1-patients (1-year: V0: 100%; V1: 70.6%; p-value = 0.012) (3-year: V0: 95.2%; V1: 46.2%; p-value = 0.002) (5-year: V0: 90.5%; V1: 36.4%; p-value = 0.003). CONCLUSION: As we have shown with our investigations, V1 has a major impact on long-term survival in NSCLC patients and furthermore, acts as an independent risk factor. Due to our small but specified sample size, our statement should be confirmed by a multicenter study. In the meantime, we suggest making the implementation of the V0/V1 specification mandatory in the tumor classification.

Different pulmonary adenocarcinoma growth patterns significantly affect survival.

OBJECTIVE: Adenocarcinoma (AC) is the number one pathological entity of lung cancer with approximately 30-40% of cases. It is known to be heterogeneous and has 5 histopathological growth patterns. We evaluated the long-term survival rates of patients with predominant subtypes. METHODS: 290 patients with AC underwent pulmonary resection between 2012 and 2017 at our institution. We excluded all patients with lymph node involvement and distant metastases. Hence, 163 patients were included for further analysis. Predominant growth pattern was defined if more than 10% of cells showed a growth pattern. 1, 3, and 5-year survival rates were evaluated. Survival was assessed by Kaplan-Meier curves and the Cox proportional hazards model was used to identify prognostic factors for overall survival. RESULTS: Predominant growth patterns >10% were compared to <10% growth patterns of the same subtype. 1-year, 3-year, and 5-year overall survival rates of patients with predominant solid tumor growth >10% differed significantly from patients with <10% (88.4% vs. 97.6%, p = 0.04; 65.8% vs. 87.4% p = 0.001, 36.4% vs. 65.9% p = 0.01). Survival rates did not differ between >10% papillary and acinar growth compared to <10%. Kaplan-Meier curves showed reduced overall survival for patients with solid tumor growth >10% (log-rank 0.002). Solid tumor growth >10% was an independent prognostic factor for worse long-term survival (Hazard ratio: 3.05, p = 0.01). CONCLUSION: Our study demonstrates that the presence of a predominant solid pattern in pulmonary adenocarcinoma is a factor for an unfavorable prognosis. This should be kept in mind in daily clinical practice.

Sublobar resection without staging and lymphadenectomy for ≤2 cm Non-Small Cell Lung Cancer is no adequate therapy.

OBJECTIVE: Sublobar resection is frequently performed for Non-Small Cell Lung Cancer (NSCLC) patients with ≤2 cm nodules. Frequently, both proper staging and radical lymphadenectomy are omitted in these operations. Therefore, we decided to evaluate the number of lymph node metastases and the number of postoperative nodal upstaging in patients undergoing pulmonary resection due to NSCLC with tumors ≤2 cm at our institution. METHODS: Nodal upstaging, lymphangiosis- (L1), and hemangiosis carcinomatosa (V1) were analyzed. pN0 patients were compared to patients with postoperative nodal upstaging. One-, three, and five-year survival rates were measured. Survival was also assessed by the Kaplan-Meier method. RESULTS: 747 patients underwent surgery for NSCLC at our institution between 2012 and 2020. We retrospectively reviewed data of 236 NSCLC patients with ≤2 cm tumors. The mean tumor size was 1.4 cm ± 0.39 in our cohort. Of our patients, 14% showed a cT1a tumor, and 86% of patients cT1b. 24.0 ± 12.3 lymph nodes were dissected and analyzed per patient, and 0.7 ± 2.0 of those were affected. Of our patients, 16.1% showed L1 affection, and 7.6% a V1 affection. Lymph node involvement was diagnosed in 11(4.7%) patients preoperatively. 39(16.5%) patients were upstaged due to lymph node involvement postoperatively (p < 0.001). Upstaged patients showed significantly worse 3- (upstaged: 60.6% vs. pN0: 83.2%; p = 0.01) and 5-year (upstages: 38% vs. pN0 71.5%; p = 0.02) survival rates. CONCLUSION: 16.5% of patients with ≤2 cm NSCLC were nodal upstaged postoperatively. These results underline that lymphadenectomy and proper staging are crucial for NSCLC patients irrespective of the tumor size and the surgical approach.

Pericardial patch valve in the tricuspid position in an infant.

A 10-month-old infant with severe tricuspid valve disease due to staphylococcal bacterial endocarditis, underwent surgical replacement of the valve. The new valve was fashioned using an autologous pericardial patch. Over 3 years of follow-up, the new valve has functioned satisfactorily, with moderately elevated right atrial pressure.

Extended applications of the Amplatzer vascular plug IV in infants.

OBJECTIVE: A variety of devices are available for transcatheter closure of unwanted shunts. We describe our experience with the use of the Amplatzer vascular plug IV in a consecutive series of infants. METHODS: A total of eight consecutive infants - all born preterm at gestational ages ranging from 24 to 35 weeks - undergoing transcatheter closure of unwanted shunts - persistently patent arterial duct in five patients, an aorta to right atrium fistula in one, multiple aortopulmonary collateral vessels in one, and an azygos vein to left atrium connection in one - are described. Their age, from birth, ranged between 3 and 11 months, and weight between 2.6 and 11.3 kilograms. All devices were delivered using percutaneous arterial or venous vascular access via a large lumen (0.038 inch) 4-French delivery catheter. RESULTS: All lesions could be successfully occluded using one or more devices. Device diameters ranged between 4 and 8 millimetres, and exceeded the minimum diameter of the target vessel by 1 to 2 millimetres. Successful occlusion was confirmed either directly at angiography or on follow-up echocardiography. Of the infants who were mechanically ventilated prior to the procedure, three could be successfully weaned following closure of the shunt. There were no procedure-related complications. CONCLUSIONS: The new vascular plug IV is cheap and efficacious in closing a variety of shunts in young infants, and warrants further extended clinical application.

Perigraft reaction and incorporation of porcine and bovine pericardial patches.

OBJECTIVES: Bovine and porcine pericardial patches are frequently used in cardiothoracic and vascular surgery. There are no guidelines recommending the usage of these patches for particular surgical approaches. However, these 2 materials supposedly possess different properties. The clinical advantage of porcine compared with bovine patches remains controversial. In this experimental study, we analysed the incorporation and vascularization of bovine and porcine pericardial patches during the initial phase after implantation. METHODS: Bovine and porcine pericardial patches were implanted into the dorsal skinfold chamber of C57BL/6 mice (n = 8 per group) to study vascularization and inflammation at the implantation site using repetitive intravital fluorescence microscopy over a 14-day period. At the end of the in vivo experiments, CD-31-positive cells were determined to evaluate the vascularization by immunohistochemistry. Furthermore, cell proliferation and apoptosis were analysed immunohistochemically. RESULTS: Implanted bovine patches exhibited an enhanced vascularization, as indicated by a significantly higher number of CD-31-positive cells and micro-vessels (23.2 ± 4.3 vs 16.5 ± 5.8 mm-2; P = 0.001). Furthermore, bovine patches showed a slightly but not significantly higher functional capillary density. Both patches induced a moderate leukocytic inflammatory host tissue response, and neither bovine nor porcine patches significantly affected apoptosis and cell proliferation at the implantation site. CONCLUSIONS: Bovine and porcine pericardial patches are similarly suitable for surgery. Bovine patches exhibited an improved vascularization during the first 14 days after implantation. This may result in a quicker and improved incorporation into the surrounding tissue compared with porcine pericardial patches.

A Novel Restorative Pulmonary Valve Conduit: Early Outcomes of Two Clinical Trials.

Objectives: We report the first use of a biorestorative valved conduit (Xeltis pulmonary valve-XPV) in children. Based on early follow-up data the valve design was modified; we report on the comparative performance of the two designs at 12 months post-implantation. Methods: Twelve children (six male) median age 5 (2 to 12) years and weight 17 (10 to 43) kg, had implantation of the first XPV valve design (XPV-1, group 1; 16 mm (n = 5), and 18 mm (n = 7). All had had previous surgery. Based on XPV performance at 12 months, the leaflet design was modified and an additional six children (five male) with complex malformations, median age 5 (3 to 9) years, and weight 21 (14 to 29) kg underwent implantation of the new XPV (XPV-2, group 2; 18 mm in all). For both subgroups, the 12 month clinical and echocardiographic outcomes were compared. Results: All patients in both groups have completed 12 months of follow-up. All are in NYHA functional class I. Seventeen of the 18 conduits have shown no evidence of progressive stenosis, dilation or aneurysm formation. Residual gradients of >40 mm Hg were observed in three patients in group 1 due to kinking of the conduit (n = 1), and peripheral stenosis of the branch pulmonary arteries (n = 2). In group 2, one patient developed rapidly progressive stenosis of the proximal conduit anastomosis, requiring conduit replacement. Five patients in group 1 developed severe pulmonary valve regurgitation (PI) due to prolapse of valve leaflet. In contrast, only one patient in group 2 developed more than mild PI at 12 months, which was not related to leaflet prolapse. Conclusions: The XPV, a biorestorative valved conduit, demonstrated promising early clinical outcomes in humans with 17 of 18 patients being free of reintervention at 1 year. Early onset PI seen in the XPV-1 version seems to have been corrected in the XPV-2, which has led to the approval of an FDA clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02700100 and NCT03022708.

Different Responses to Drug Safety Screening Targets between Human Neonatal and Infantile Heart Tissue and Cardiac Bodies Derived from Human-Induced Pluripotent Stem Cells.

AIMS: Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) have become a promising tool in cardiovascular safety pharmacology. Immaturity of iPS-CMs remains an ongoing concern. We compared electrophysiological and contractile features of cardiac bodies (hiPS-CBs) derived from human-induced pluripotent stem cells and human neonatal and infantile myocardial slices relevant for drug screening. METHODS AND RESULTS: Myocardial tissue slices were prepared from biopsies obtained from patients undergoing surgery for hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). Electrophysiological features and response to Ik,r blockade as well as contractile properties were investigated using microelectrodes and isometric force measurements and were compared to hiPS-CBs. Both native myocardial tissue slices as well as hiPS-CBs showed action potential prolongation after Ik,r blockade, but early afterdepolarisations could be observed in native myocardial tissue slices only. The force-frequency relationship (FFR) varied at lower frequencies and was negative throughout at higher frequencies in hiPS-CBs. In contrast, native myocardial tissue slices exhibited positive, negative, and biphasic FFRs. In contrast to native myocardial tissue slices, hiPS-CBs failed to show an inotropic response to ß-adrenergic stimulation. Although all groups showed ß-adrenergic induced positive lusitropy, the effect was more pronounced in myocardial tissue slices. CONCLUSION: hiPS-CBs were able to reproduce AP prolongation after Ik,r blockade, but to a lesser extent compared to human neonatal and infantile myocardial tissue slices. Early afterdepolarisations could not be induced in hiPS-CBs. Contractile force was differently regulated by ß-adrenergic stimulation in hiPS-CBs and the native myocardium. If used for cardiotoxicity screening, caution is warranted as hiPS-CBs might be less sensitive to pharmacologic targets compared to the native myocardium of neonates and infants.

Outcomes and factors associated with early mortality in pediatric and neonatal patients requiring extracorporeal membrane oxygenation for heart and lung failure.

BACKGROUND: Mortality and morbidity after surgical repair for complex congenital heart defects and severe cardiopulmonary failure on extracorporeal membrane oxygenation (ECMO) support remain high despite significant advances in medical management and technological improvements. We report on outcomes and factors after using ECMO in our surgical pediatric population including short- and long-term survival. METHODS: A total of 45 neonatal and pediatric patients were identified who needed ECMO in our department between January 2008 and December 2016. In 41 cases (91%) a vaECMO (ECLS) was implemented, whereas 4 patients (9%) received vvECMO treatment for respiratory failure. In 33 cases vaECMO was implanted following cardiac surgery for congenital heart disease (CHD), whereas in 8 patients ECMO was utilized by means of extracorporeal cardiopulmonary resuscitation (eCPR) following refractory cardiac arrest. The primary endpoint of the present study was survival to discharge and long-term survival free from neurological impairments. Univariate and bivariate analysis was performed to address predictors for outcome. Kaplan-Meier survival analysis was used to address mid- and long-term survival. RESULTS: Median [IQR] duration of ECMO support was 3 [2, 5] days (range, 1-17 days). Median age at ECMO implantation was 128 [14, 1,813] days, median weight of patients was 5.4 [3.3, 12] kg. Totally 10 patients included in this study were diagnosed with concomitant genetic conditions. A total of 20 (44%) patients were successfully weaned off ECMO (survived >24 h after ECMO explantation), whereas 15 (33%) of them survived to discharge. Single ventricle (SV) repair was performed in 14, biventricular repair in 19 patients. Neonates (<30 days of age), female patients, patients with genetic conditions, SV repair patients, and eCPR patient cohort showed lower odds of survival on ECMO. Failed myocardial recovery (P=0.001), profound circulatory failure despite a high dose of catecholamines (P<0.001), neurological impairment pre-ECMO and post-ECMO (P=0.04 and P<0.001, respectively), and severe pulmonary failure despite high respiratory pressure settings were most common mortality reasons. CONCLUSIONS: ECMO provides efficient therapy opportunities for life-threatening conditions. Nevertheless, neonates and pediatric patients who underwent ECMO were at high risk for cerebrovascular events and poor survival. Appropriate patient selection using predictors of outcome reducing complications might improve outcomes of this patient cohort.

Atrioventricular block following implantation of a stent in the oval fossa.

A neonate weighing 2.8 kilograms underwent the staged hybrid procedure for palliation of hypoplastic left heart syndrome. Within 6 hours following placement of a stent to retain patency of the interatrial communication, the infant developed second degree atrioventricular block, which resolved within 24 hours. Four days later, the patient developed complete atrioventricular dissociation. Removal of the stent was followed by recovery of atrioventricular conduction.