Stroke Complications in Patients Requiring Durable Mechanical Circulatory Support Systems After Extracorporeal Life Support.

Stroke is one of the leading complications following durable mechanical circulatory support (MCS) implantation. The aim of this multicenter study was to investigate stroke complications in patients requiring durable MCS following extracorporeal life support (ECLS). Data of 11 high volume MCS centers were collected and evaluated to identify patients who underwent durable MCS implantation after ECLS support between January 2010 and August 2018. The primary outcome was stroke following durable MCS implantation. Univariate and multivariate logistic regression analyses were performed to determine predictors of stroke. Overall, 531 patients met the inclusion criteria. Only patients who were supported with continuous flow pumps were included in this study accounting for 495 patients (median age 54 years old [interquartile range 47-60]). A total of 136 patients (27%) developed postoperative stroke on device during the follow-up (48% ischemic and 52% hemorrhagic) after a median durable MCS support of 320 [32-1,000] days, accounting for 0.17 events per patient-year. Of 133 patients with known date of stroke, a total of 47 (10%) developed stroke during the first 30 days (64% ischemic and 36% hemorrhagic), and 86 patients developed stroke after 30 days (38% ischemic and 62% hemorrhagic) of durable MCS support (late stroke). Survival rate was significantly lower in patients with hemorrhagic stroke ( p = 0.00091). Stroke appears to be a common complication in patients transitioned to durable MCS support after ECLS. Hemorrhagic stroke is a more common type of late stroke and is associated with inferior outcomes.

Left ventricular assist device implants in patients on extracorporeal membrane oxygenation: do we need cardiopulmonary bypass?

OBJECTIVES: Implanting a durable left ventricular assist device (LVAD) in a patient on extracorporeal life support (ECLS) is challenging. The goal of this study was to compare the results of patients from a European registry who had a durable LVAD implanted with or without transition from ECLS to cardiopulmonary bypass (CPB). METHODS: A total of 531 patients on ECLS support who had an LVAD implant between January 2010 and August 2018 were analysed; after 1:1 propensity score matching, we identified and compared 175 patients in each group. RESULTS: The duration of preoperative ECLS was 7 [standard deviation (SD) 6] vs 7 (SD 6) days in patients with or without CPB (P = 0.984). The surgical time was longer in the CPB group [285 (SD 72) vs 209 [SD 75] min; P ≤ 0.001). The postoperative chest tube output was comparable [1513 (SD 1311) vs 1390 (SD 1121) ml; P = 0.3]. However, re-exploration for bleeding was necessary in 41% vs 29% of patients with or without CPB (P = 0.01) and a significantly higher number of packed red blood cells and fresh frozen plasma [8 (SD 8) vs 6 (SD 4) units; P = 0.001 and 6 (SD 7) vs 5 (SD 5) units; P = 0.03] were administered to patients operated on with CPB. A postoperative mechanical right ventricular support device was necessary in 50% vs 41% of patients (P = 0.08). The stroke rate was not significantly different (P 0.99). No difference in survival was observed. CONCLUSIONS: Omitting CPB for an LVAD implant in patients on ECLS is safe and results in shorter operating time, less re-exploration for bleeding and fewer blood products. However, no survival benefit is observed.

Impact of extra-corporeal life support (ECLS) cannulation strategy on outcome after durable mechanical circulation support system implantation on behalf of durable MCS after ECLS Study Group.

BACKGROUND: The literature on outcomes of patients requiring durable mechanical circulatory support (MCS) after extra-corporeal life support (ECLS) is limited. The aim of this study was to investigate the impact of preoperative ECLS cannulation on postoperative outcome after durable MCS implantation. METHODS: The durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent durable MCS implantation after ECLS between January 2010 and August 2018 in eleven high volume European centers. Patients who underwent the implantation of total artificial heart, pulsatile pumps, or first-generation pumps after ECLS were excluded from the analysis. The remaining patients were divided into two groups; central ECLS group (cECLS) and peripheral ECLS group (pECLS). A 1:1 propensity score analysis was performed to identify two matched groups. The outcome of these two groups was compared. RESULTS: A total of 531 durable MCS after ECLS were implanted during this period. The ECLS cannulation site was peripheral in 87% (n=462) and central in 13% (n=69) of the patients. After excluding pulsatile pumps and total artificial heart patients, a total of 494 patients remained (pECLS =434 patients, cECLS =60 patients). A 1:1 propensity score analysis resulted in 2 matched groups (each 55 patients) with median age of 54 years (48-60 years) in cECLS group and 54 years (43-60 years) in pECLS group. HeartWare HVAD (Medtronic, Minneapolis, MN) was implanted in the majority of the patients (cECLS =71% vs. pECLS =76%, P=0.67). All postoperative morbidities were comparable between the groups. The thirty-day, one year and long-term survival was comparable between the groups (P=0.73). CONCLUSIONS: The cannulation strategy of ECLS appears to have no impact on the post-operative outcome after durable MCS implantation.

Impact of a surgical approach for implantation of durable left ventricular assist devices in patients on extracorporeal life support.

BACKGROUND: The aim of this study was to evaluate the impact of the surgical approach on the postoperative outcome in patients who underwent left ventricular assist device (LVAD) implantation after having received veno-arterial extracorporeal life support (va-ECLS) using data from a European registry (ECLS-VAD). Five hundred and thirty-one patients were included. METHODS: A propensity score-adjusted outcome analysis was performed, resulting in 324 patients in the full sternotomy (FS) group and 39 in the less invasive surgery (LIS) group. RESULTS: The surgery lasted in median 236 min in the FS group versus 263 min in the LIS group (p = 0.289). The median chest tube output during the first 24 h was similar in both groups. Patients who underwent implantation with an FS required more blood products during the first 24 postoperative hours (median 16 vs. 12, p = 0.033). The incidence of revision due to bleeding was also higher (35.5 vs. 15.4%, p = 0.016). A temporary postoperative right ventricular assist device was necessary in 45.1 (FS) versus 23.1% (LIS) of patients, respectively (p = 0.067). No stroke occurred in the LIS group during the first 30 days after surgery (7.4% in the FS group). The incidence of stroke and of renal, hepatic, and respiratory failure during the follow-up was similar in both groups. The 30-day and one-year survival were similar in both groups. CONCLUSION: LIS for implantation of a durable LVAD in patients on va-ECLS implanted for cardiogenic shock is associated with less revision due to bleeding, less administration of blood products and absence of perioperative stroke, with no impact on survival.

Transition From Temporary to Durable Circulatory Support Systems.

BACKGROUND: The decision to implant durable mechanical circulatory systems (MCSs) in patients on extracorporeal life support (ECLS) is challenging due to expected poor outcomes in these patients. OBJECTIVES: The aim of this study was to identify outcome predictors that may facilitate future patient selection and decision making. METHODS: The Durable MCS after ECLS registry is a multicenter retrospective study that gathered data on consecutive patients who underwent MCS implantation after ECLS between January 2010 and August 2018 in 11 high-volume European centers. Several perioperative parameters were collected. The primary endpoint was survival at 1 year after durable MCS implantation. RESULTS: A total of 531 durable MCSs after ECLS were implanted during this period. The average patient age was 53 ± 12 years old. ECLS cannulation was peripheral in 87% of patients and 33% of the patients had history of cardiopulmonary resuscitation before ECLS implantation. The 30-day, 1-year, and 3-year actuarial survival rates were 77%, 53%, and 43%, respectively. The following predictors for 1-year outcome have been observed: age, female sex, lactate value, Model of End-Stage Liver Disease XI score, history of atrial fibrillation, redo surgery, and body mass index >30 kg/m2. On the basis of this data, a risk score and an app to estimate 1-year mortality was created. CONCLUSIONS: The outcome in patients receiving durable MCS after ECLS remains limited, yet preoperative factors may allow differentiating futile patients from those with significant survival benefit.

Ventricular assist device in a patient with congenitally corrected transposition of the great arteries and situs inversus totalis.

Congenitally corrected transposition of the great arteries and situs inversus totalis are rare congenital anomalies. While congenital heart diseases affect about 0.75%-0.9% of newborns, less than 1% of them have congenitally corrected transposition of the great arteries. Meanwhile, the incidence of situs inversus totalis is about 0.01%. This is a case report of a patient with congenitally corrected transposition of the great arteries and situs inversus totalis who was supported with a ventricular assist device, resulting in a challenging clinical scenario.

Role for Artemis nuclease in the repair of radiation-induced DNA double strand breaks by alternative end joining.

Exposure of cells to ionizing radiation or radiomimetic drugs generates DNA double-strand breaks that are processed either by homologous recombination repair (HRR), or by canonical, DNA-PKcs-dependent non-homologous end-joining (C-NHEJ). Chemical or genetic inactivation of factors involved in C-NHEJ or HRR, but also their local failure in repair proficient cells, promotes an alternative, error-prone end-joining pathway that serves as backup (A-EJ). There is evidence for the involvement of Artemis endonuclease, a protein deficient in a human radiosensitivity syndrome associated with severe immunodeficiency (RS-SCID), in the processing of subsets of DSBs by HRR or C-NHEJ. It is thought that within HRR or C-NHEJ Artemis processes DNA termini at complex DSBs. Whether Artemis has a role in A-EJ remains unknown. Here, we analyze using pulsed-field gel electrophoresis (PFGE) and specialized reporter assays, DSB repair in wild-type pre-B NALM-6 lymphocytes, as well as in their Artemis(-/-), DNA ligase 4(-/-) (LIG4(-/-)), and LIG4(-/-)/Artemis(-/-) double mutant counterparts, under conditions allowing evaluation of A-EJ. Our results substantiate the suggested roles of Artemis in C-NHEJ and HRR, but also demonstrate a role for the protein in A-EJ that is confirmed in Artemis deficient normal human fibroblasts. We conclude that Artemis is a nuclease participating in DSB repair by all major repair pathways.