A novel method of transapical ProtekDuo rapid deployment cannula as temporary left ventricular assist device.

Peripheral extracorporeal membrane oxygenation (ECMO) is one of the most common strategies for cardiogenic shock. ECMO cannulation is associated with an increased risk of complications. We describe a minimally invasive, off-pump technique to provide adequate hemodynamic support and left ventricular unloading. A 54-year-old male with nonischemic cardiomyopathy and severe peripheral vascular disease with cardiogenic shock was initially supported with inotropes and an intra-aortic balloon pump. Despite continued support, he continued to deteriorate, and we escalated to a temporary left ventricular support with a CentriMag, using a transapical ProtekDuo Rapid Deployment cannula via mini left-thoracotomy. This approach provides adequate hemodynamic support, left ventricular unloading and early ambulation. After 9 days, the patient's functional status was improved and was medically optimized. The patient received a left ventricular assist device as destination therapy. He was discharged home, resumed his normal activities and has been doing well for more than 27 months.

HLA Sensitization in Patients Bridged to Lung Transplantation With Extracorporeal Membrane Oxygenation.

Lung transplantation is a definitive therapy for many end-stage lung pathologies. Extracorporeal membrane oxygenation (ECMO) is increasingly being used as a bridge to lung transplantation (BTT). HLA sensitization is a major barrier to lung transplantation. The development of HLA sensitization while undergoing ECMO support as a BTT has recently been reported in a 2-patient series. Methods: We performed a retrospective analysis of patients undergoing ECMO as a BTT at a single large academic medical center from January 2016 to April 2022. The study was approved by the institutional review board. We selected patients who had undergone ECMO support for at least 7 d with either negative HLA before cannulation or initial negative HLA on ECMO (3 patients). Results: We identified 27 patients bridged to lung transplantation with available HLA data. Of this group, 8 patients (29.6%) developed significant HLA sensitization (>10%). We did not identify any factors predisposing to sensitization, including infection episodes or blood product transfusion. Sensitized patients demonstrated a trend toward an increased primary graft dysfunction rate, a need for posttransplant ECMO support, and a decreased 1-y survival; however, these did not meet statistical significance. Conclusions: Our study is the largest series today describing the association between HLA sensitization and ECMO therapy. We suggest that interaction between the immune system and ECMO circuit contributes to allosensitization pretransplant, similar to that occurring with ventricular assist device. Further work is needed to better characterize the incidence of HLA sensitization in a multicenter cohort and to identify potentially modifiable factors associated with HLA sensitization.

Low molecular weight hyaluronan inhibits lung epithelial ion channels by activating the calcium-sensing receptor.

Herein, we tested the hypothesis that low molecular weight hyaluronan (LMW-HA) inhibits lung epithelial ions transport in-vivo, ex-vivo, and in-vitro by activating the calcium-sensing receptor (CaSR). Twenty-four hours post intranasal instillation of 50-150 µg/ml LMW-HA to C57BL/6 mice, there was a 75% inhibition of alveolar fluid clearance (AFC), a threefold increase in the epithelial lining fluid (ELF) depth, and a 20% increase in lung wet/dry (W/D) ratio. Incubation of human and mouse precision cut lung slices with 150 µg/ml LMW-HA reduced the activity and the open probability (Po) of epithelial sodium channel (ENaC) in alveolar epithelial type 2 (ATII) cells, and in mouse tracheal epithelial cells (MTEC) monolayers as early as 4 h. The Cl- current through cystic fibrosis transmembrane conductance regulator (CFTR) and the activity of Na,K-ATPase were both inhibited by more than 66% at 24 h. The inhibitory effects of LMW-HA on ion channels were reversed by 1 µM NPS-2143, or 150 µg/ml high molecular weight hyaluronan (HMW-HA). In HEK-293 cells expressing the calcium-sensitive Cl- channel TMEM16-A, CaSR was required for the activation of the Cl- current by LMW-HA. This is the first demonstration of lung ions and water transport inhibition by LMW-HA, and its mediation through the activation of CaSR.

Repair of Tracheal Dehiscence After Heart-Lung Transplant Complicated by SARS-CoV-2 Infection.

Airway complications are a major cause of morbidity after thoracic transplantation. Airway ischemia, necrosis, and tracheobronchial anastomotic dehiscence are associated with early mortality. We describe a case of tracheal anastomotic dehiscence after en bloc heart-lung transplant complicated by severe acute respiratory syndrome coronavirus 2 infection. Timely surgical management and reconstruction with a bovine pericardial patch and double muscle flap were performed. After 8 months of follow-up, there are no airway complications and normalized allograft function.

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report.

Initial experience with lung transplant of COVID-19-positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.

Utility of transesophageal echocardiography to assess real time left atrial pressure changes and dynamic mitral regurgitation following placement of transseptal multistage venous cannula for systemic venous drainage and indirect left ventricular venting in venoarterial extracorporeal membrane oxygenation.

A patient with heart failure due to nonischemic cardiomyopathy presented as a transfer to our institution following peripheral (femoral) venoarterial (VA) extracorporeal membrane oxygenation (ECMO) placement. With peripheral VA ECMO cannulation, the patient continued to have unstable ventricular tachyarrhythmias. Echocardiography demonstrated left ventricular (LV) dilation and severe mitral regurgitation (MR) with clinical and chest X-ray evidence of pulmonary edema. To provide venous drainage and simultaneous decompression of the left atrium (LA) and thereby indirect LV venting, a single multistage venous cannula was placed across the inter-atrial septum (IAS) using the previously described left atrial venoarterial (LA-VA) ECMO cannulation technique. Two- and three-dimensional (3D) transesophageal echocardiography (TEE) demonstrated utility in guiding cannula placement into the appropriate position and providing real time assessment of ventricular decompression and MR severity. There was subsequent improvement in pulmonary edema. This case is thought to be the first demonstration of real time resolution of pulmonary venous flow reversal in a patient undergoing LA-VA ECMO cannulation. This demonstration offers important mechanistic insight into some of the potential benefits of such an approach.

Persistent mitral regurgitation after left ventricular assist device: a clinical conundrum.

AIMS: Persistent mitral valve regurgitation (MR) after continuous flow left ventricular assist device implantation (cfLVAD) is associated with pulmonary hypertension and right ventricular failure with variable effects on survival across published studies. The aim of this study is to determine the incidence and predictors of persistent MR at 6-month follow-up after cfLVAD implantation and its impact on survival, haemodynamics, right ventricular function, and morbidity. METHODS AND RESULTS: We performed a retrospective review of all adult cfLVAD recipients from January 2012 to June 2017 at a single tertiary university hospital with follow-up until April 2019. Primary outcome was to compare survival between patients with no-to-mild compared with persistent moderate-to-severe MR at 6 months. Secondary outcomes included right heart failure (RHF), length of stay, re-hospitalizations, and composite of death, transplant, and pump exchange during the length of follow-up. Final analytic sample was 111 patients. The incidence of persistent moderate or severe MR at 6 months was 26%. Significant predictors of persistent MR at 6 months were left atrium dimension and volume. The group with persistent moderate-to-severe MR at 6 months had higher incidence of RHF at 6 months (45% vs. 25%, P = 0.04). There was no difference in survival at 1 year between the groups (no-to-mild MR 85.5%, moderate-to-severe MR 87.9%, Wilcoxon P-value = 0.63). There was no difference in re-hospitalizations, length of stay, composite of death, transplant, or pump exchange during the length of follow-up between the comparison groups. CONCLUSIONS: Persistent moderate-to-severe MR after cfLVAD implantation is present in one fourth of patients and is associated with increased incidence of RHF, higher mean pulmonary pressure, and pulmonary capillary wedge pressure with no effect on 1 year survival. Increased left atrium size was associated with persistent moderate-to-severe MR at 6 months.

Management of reproductive health after cardiac transplantation.

Pregnancy after cardiac transplantation poses immense challenges. Maternal risks include hypertensive disorders of pregnancy, rejection, and failure of the cardiac allograft that may lead to death. Fetal risks include potential teratogenic effects of immunosuppression and prematurity. Because of the high-risk nature of pregnancy in a heart transplant patient, management of reproductive health after cardiac transplantation should include preconception counseling to all women in the reproductive age group before and after cardiac transplantation. Reliable contraception is vital as nearly half of the pregnancies in this population are unintended. Despite the associated risks, successful pregnancies after cardiac transplantation have been reported. A multidisciplinary approach proposed in this review is essential for successful outcomes. A checklist for providers to guide management is provided.

Extracorporeal membrane oxygenation in the management of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA, also known as Wegener's granulomatosis) is a type of systematic vasculitis that primarily involves the lung and kidney. Diffuse alveolar hemorrhage (DAH) and associated acute respiratory failure are uncommon but devastating complications of GPA. Experience in using extracorporeal membrane oxygenation (ECMO) to manage DAH caused by GPA is limited. We report two GPA patients with DAH that were successfully managed using ECMO support. Examining 13 cases identified in the literature and two of our own, we observed that most patients experienced rapid deterioration in respiratory function in conjunction with a precedent respiratory infection. All 15 patients received veno-venous ECMO support. The median duration of ECMO support was 11 days (interquartile range: 7.5-20.75 days). Bleeding was the most common complication, seen in four (26.7%) cases. All patients were successfully weaned off ECMO after a median length of hospital stay of 42 days (interquartile range: 30-78 days). We demonstrated that the use of ECMO is a reasonable and effective support option in the management of GPA patients with DAH. The risk of bleeding is high but maybe reduced using a lower anticoagulation goal.

Femoral venoarterial extracorporeal membrane oxygenation using a novel biatrial cannula for venous drainage and left ventricular venting.

Extracorporeal life support (ECLS) is an expanding technology for patients in cardiogenic shock. The majority of patients requiring ECLS can be managed with percutaneous venoarterial (VA) femoral cannulation. Despite sufficient extracorporeal circulatory support, a unclear number of patients develop left ventricular distension which can result in increased wall tension and stress as well as worsening pulmonary edema. Indications to vent the left ventricle can be controversial. When venting is indicated, a number of additional procedures may be considered including inotropic support, intra-aortic balloon pump, impella, balloon atrial septostomy, or placement of a transseptal cannula. We present a unique case of a femoral VA extracorporeal membrane oxygenation as a bridge to transplant with left-sided venting using a Bio-Medicus NextGen cannula (Medtronic) with a transseptal approach.

Pedicle flap coverage for infected ventricular assist device augmented with dissolving antibiotic beads: Creation of an antibacterial pocket.

Infectious complications following left ventricular assist device implantation can carry significant morbidity and mortality. The main tenet of treatment is source control which entails local wound care, intravenous antimicrobial therapy, surgical debridement, and at times, soft tissue flap coverage. The mode of therapy depends on the severity, etiology, and location of infection as well as the clinical status of the patient. We describe a case of a 46-year-old male who underwent left ventricular assist device placement complicated by pump thrombosis, recurrent infection, and hardware exposure who was successfully treated with a novel method of staged, soft tissue reconstruction.

Peripheral femoral venoarterial extracorporeal membrane oxygenation as bridge to heart-lung transplant omne iter incipit primus.

Heart-lung transplant (HLT) is a widely accepted modality for certain patients with advanced and refractory cardiopulmonary disease. Some of these patients are critically ill on the transplant waiting list, and venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be used as a bridge to transplantation. Although the experience with ECMO as a bridge to lung transplant is promising, there is limited evidence to use ECMO as a bridge to HLT. Femoral cannulation remains a concern for ambulation given the risk of bleeding and cannula complications despite studies reporting its safety. We present a case of a 56-year-old male with interstitial lung disease and severe secondary pulmonary hypertension, who was successfully bridged to HLT with ambulatory femoral VA-ECMO.

Clinical characteristics and outcomes of patients requiring prolonged inotropes after left ventricular assist device implantation.

Limited data exist regarding patients with continuous-flow left ventricular assist device (LVAD) support who require long-term inotropes. Our primary objective was to evaluate the clinical characteristics and all-cause mortality of LVAD recipients with prolonged inotrope use (PIU). Secondary endpoints were to compare predictors of PIU, mortality, risk of late re-initiation of inotropes, time to gastrointestinal bleed (GIB), infection, and arrhythmias. Retrospective cohort study was conducted on adult patients with primary continuous-flow LVADs implanted from January 2008 to February 2017 and the patients were followed up through February 2018. We defined PIU as ≥14 days of inotrope support. Kaplan-Meier method, competing risk models and Cox proportional hazard models were used. Final analytic sample was 203 patients, 58% required PIU, and 10% were discharged on inotropes. There was no difference in preimplant characteristics. One-year survival rate was 87% if no PIU required, 74% if PIU required, and 72% if discharged on inotropes. PIU was associated with longer length of stay and higher incidence of GIB. We found no association between PIU and late re-initiation of inotropes, infection or arrhythmias. Adjusted hazard risk of death was increased in patients with PIU (HR = 1.66, P = .046), older age (HR = 1.28, P = .031), and higher creatinine levels (HR = 1.60, P = .007). Prolonged inotrope use is frequently encountered following LVAD implantation and is associated with adverse prognosis but remains a therapeutic option. Inability to wean inotropes prior to hospital discharge is a marker of patients at particularly higher risk of mortality following LVAD implantation.

Bridging to lung transplantation with double-lumen venovenous extracorporeal membrane oxygenation.

BACKGROUND: Double-lumen venovenous extracorporeal membrane oxygenation may be used as a bridge to lung transplantation. Predictors of outcome with this strategy have not been well described. METHODS: All patients with irreversible lung disease who developed acute pulmonary failure and required double-lumen venovenous extracorporeal membrane oxygenation as a bridge to decision or lung transplant at our institution were included in this study. Survival of the extracorporeal membrane oxygenation patients was compared with listed patients who did not require extracorporeal membrane oxygenation with lung allocation score in the highest 10% for the same period. RESULTS: Fifteen patients (46 ± 17 years old) received double-lumen venovenous extracorporeal membrane oxygenation cannula. Mean length of extracorporeal membrane oxygenation support was 18.2 (1-60) days. Of these, seven patients were bridged to lung transplant, six died on extracorporeal membrane oxygenation, and two weaned to recovery. Amount of red blood cell transfusion was significantly higher (3.3 vs 18.5 U, p = 0.003) and lowest oxygen saturation was significantly lower in non-survivors (84.5% vs 66.3%, p = 0.002). Of the seven patients who were already listed for lung transplant at the onset of extracorporeal membrane oxygenation, five were transplanted. Overall survival to hospital discharge was 60%. Survival of patients with lung allocation score in the highest 10% (average lung allocation score 83.4) in the same period was 80%. CONCLUSION: Double-lumen venovenous extracorporeal membrane oxygenation cannula is a feasible option to bridge patients to decision or lung transplantation. Blood transfusion requirement and low oxygen saturation are markers of poor prognosis. Listing status at the time of cannulation and ambulation during extracorporeal membrane oxygenation support may be important indicators of good outcome.

Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model.

BACKGROUND: Continuous-flow ventricular assist devices (CF-VADs) produce non-physiologic flow with diminished pulsatility, which is a major risk factor for development of adverse events, including gastrointestinal (GI) bleeding and arteriovenous malformations (AVMs). Introduction of artificial pulsatility by modulating CF-VAD flow has been suggested as a potential solution. However, the levels of pulsatility and frequency of CF-VAD modulation necessary to prevent adverse events are currently unknown and need to be evaluated. METHODS: The purpose of this study was to use human aortic endothelial cells (HAECs) cultured within an endothelial cell culture model (ECCM) to: (i) identify and validate biomarkers to determine the effects of pulsatility; and (ii) conclude whether introduction of artificial pulsatility using flow-modulation approaches can mitigate changes in endothelial cells seen with diminished pulsatile flow. Nuclear factor erythroid 2-related factor 2 (Nrf-2)-regulated anti-oxidant genes and proteins and the endothelial nitric oxide synthase/endothelin-1 (eNOS/ET-1) signaling pathway are known to be differentially regulated in response to changes in pulsatility. RESULTS: Comparison of HAECs cultured within the ECCM (normal pulsatile vs CF-VAD) with aortic wall samples from patients (normal pulsatile [n = 5] vs CF-VADs [n = 5]) confirmed that both the Nrf-2-activated anti-oxidant response and eNOS/ET-1 signaling pathways were differentially regulated in response to diminished pulsatility. Evaluation of 2 specific CF-VAD flow-modulation protocols to introduce artificial pulsatility, synchronous (SYN, 80 cycles/min, pulse pressure 20 mm Hg) and asynchronous (ASYN, 40 cycles/min, pulse pressure 45 mm Hg), suggested that both increased expression of Nrf-2-regulated anti-oxidant genes and proteins along with changes in levels of eNOS and ET-1 can potentially be minimized with ASYN and, to a lesser extent, with SYN. CONCLUSIONS: HAECs cultured within the ECCM can be used as an accurate model of large vessels in patients to identify biomarkers and select appropriate flow-modulation protocols. Pressure amplitude may have a greater effect in normalizing anti-oxidant response compared with frequency of modulation.