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.

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.

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.

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.

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.

Delayed sternal closure does not reduce complications associated with coagulopathy and right ventricular failure after left ventricular assist device implantation.

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 patients who had immediate sternal closure (IC). Mean Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level of IC group and DSC group were 2.7 and 2.6, respectively. Postoperative bleeding (643 vs. 1469 ml, p < 0.001), duration of inotropic support (109 vs. 172 h, p = 0.034), and time to extubation (26 vs. 52 h, p = 0.005) were significantly increased in DSC group. Length of ICU stay (14 vs. 15 days, p = 0.234) and hospital stay (28 vs. 20 days, p = 0.145) were similar. Incidence of right ventricular failure and tamponade were similar in the two groups. Routine DSC after implantation of an LVAD did not prove to be beneficial in reducing complications associated with coagulopathy and hemodynamic instability including cardiac tamponade or right ventricular failure. We suggest that DSC be selectively applied for patients undergoing LVAD implant.

Myocardial relaxation is accelerated by fast stretch, not reduced afterload.

Fast relaxation of cross-bridge generated force in the myocardium facilitates efficient diastolic function. Recently published research studying mechanisms that modulate the relaxation rate has focused on molecular factors. Mechanical factors have received less attention since the 1980s when seminal work established the theory that reducing afterload accelerates the relaxation rate. Clinical trials using afterload reducing drugs, partially based on this theory, have thus far failed to improve outcomes for patients with diastolic dysfunction. Therefore, we reevaluated the protocols that suggest reducing afterload accelerates the relaxation rate and identified that myocardial relengthening was a potential confounding factor. We hypothesized that the speed of myocardial relengthening at end systole (end systolic strain rate), and not afterload, modulates relaxation rate and tested this hypothesis using electrically-stimulated trabeculae from mice, rats, and humans. We used load-clamp techniques to vary afterload and end systolic strain rate independently. Our data show that the rate of relaxation increases monotonically with end systolic strain rate but is not altered by afterload. Computer simulations mimic this behavior and suggest that fast relengthening quickens relaxation by accelerating the detachment of cross-bridges. The relationship between relaxation rate and strain rate is novel and upends the prevailing theory that afterload modifies relaxation. In conclusion, myocardial relaxation is mechanically modified by the rate of stretch at end systole. The rate of myocardial relengthening at end systole may be a new diagnostic indicator or target for treatment of diastolic dysfunction.

Safety of Nurse-Led Ambulation for Patients on Venovenous Extracorporeal Membrane Oxygenation.

PURPOSE: Venovenous extracorporeal membrane oxygenation (VV ECMO) is an effective therapy in patients with acute lung injury and end-stage lung disease. Although immobility increases the risk of complications, ambulation of patients on VV ECMO is not the standard of care in many institutions. Staff concerns for patient safety remain a barrier to ambulation. In this case series, we present our experience utilizing a nurse-driven ambulatory VV ECMO process to safely rehabilitate patients. METHODS: We retrospectively reviewed all VV ECMO cases at our institution between January 1, 2011, and November 1, 2013. Inclusion criteria for this study required patients to be cannulated in the right internal jugular vein and ambulated while on VV ECMO. RESULTS: During the period from January 1, 2011, to November 1, 2013, 18 patients (mean age 49 ± 15 years, 12 male) were ambulated while on ECMO. Eight received a transplant and survived to discharge. Of the remaining patients, 4 were successfully weaned from VV ECMO and 6 died following decisions by the family to withdraw care. The mean duration of VV ECMO support was 18 ± 16 days with the maximum duration being 61 days. All patients received physical therapy, range of motion at the bedside, and ambulated in the hospital. There were no patient falls, decannulations, or any other complications related to ambulation. CONCLUSION: The adoption of a nurse-driven program to ambulate patients on VV ECMO is safe and may reduce other complications associated with immobility.

Transmural heterogeneity of cellular level power output is reduced in human heart failure.

Heart failure is associated with pump dysfunction and remodeling but it is not yet known if the condition affects different transmural regions of the heart in the same way. We tested the hypotheses that the left ventricles of non-failing human hearts exhibit transmural heterogeneity of cellular level contractile properties, and that heart failure produces transmural region-specific changes in contractile function. Permeabilized samples were prepared from the sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricular free wall of non-failing (n=6) and failing (n=10) human hearts. Power, an in vitro index of systolic function, was higher in non-failing mid-myocardial samples (0.59±0.06µWmg(-1)) than in samples from the sub-epicardium (p=0.021) and the sub-endocardium (p=0.015). Non-failing mid-myocardial samples also produced more isometric force (14.3±1.33kNm(-2)) than samples from the sub-epicardium (p=0.008) and the sub-endocardium (p=0.026). Heart failure reduced power (p=0.009) and force (p=0.042) but affected the mid-myocardium more than the other transmural regions. Fibrosis increased with heart failure (p=0.021) and mid-myocardial tissue from failing hearts contained more collagen than matched sub-epicardial (p<0.001) and sub-endocardial (p=0.043) samples. Power output was correlated with the relative content of actin and troponin I, and was also statistically linked to the relative content and phosphorylation of desmin and myosin light chain-1. Non-failing human hearts exhibit transmural heterogeneity of contractile properties. In failing organs, region-specific fibrosis produces the greatest contractile deficits in the mid-myocardium. Targeting fibrosis and sarcomeric proteins in the mid-myocardium may be particularly effective therapies for heart failure.

Strategies and outcomes of extracorporeal membrane oxygenation use in peripartum patients: a single institution experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) use in peripartum patients is rare, and there is a gap in the literature on the outcomes and guidance on using ECMO in peripartum patients. This study describes ECMO strategies our institution uses for peripartum patients and reports outcomes of ECMO use in peripartum patients with respiratory and/or cardiac failure. METHODS: A case series of all peripartum patients, defined as pregnant or up to 6 weeks after delivery of an infant >20 weeks gestation, from 2018 to 2023 from a single center requiring ECMO support. Patients were included if ECMO was initiated in the setting of cardiac, pulmonary, or combined failure. Patient demographics, operative details, ECMO data, and adverse outcomes for maternal, fetus, and neonates were all collected. RESULTS: Eighteen patients met the inclusion criteria. The cohort had a mean maternal age of 30.7 years old and was racially diverse. A majority of this cohort tested positive for COVID-19 (n = 10, 55%). ECMO was a bridge to recovery for all patients, of whom 14 (78%) were discharged out of the hospital alive. No patients received transplantation or a durable mechanical device. The most common complications were infection (25%) and postpartum hemorrhage (22%). CONCLUSIONS: ECMO use in peripartum patients in a single tertiary center was associated with a high survival rate. Furthermore, a strong multidisciplinary team, careful reevaluation of clinical trajectory, and consideration of complications and risks associated with using ECMO in peripartum patients are possible frameworks to use when challenged with critically ill peripartum patients.

Lung transplant curriculum in pulmonary/critical care fellowship training.

BACKGROUND: Lung transplantation is an evolving specialty with the number of transplants growing annually. PURPOSE: A structured lung transplant curriculum was developed for Pulmonary/Critical Care (Pulm/CC) fellows. METHODS: Scores on pulmonary in-training examinations (ITE) 2 years prior to and 3 years after implementation were reviewed as well as completion of satisfaction surveys. RESULTS: The mean pulmonary ITE score of 1st-year fellows increased from 54.2 ± 2.5 to 63.6 ± 1.2 (M ± SD), p = .002, whereas mean pulmonary ITE score for 2nd-year fellows increased from 63.0 ± 3.0 to 70.7 ± 1.2, p = .019. The combined mean pulmonary ITE score increased from 58.6 ± 2.3 to 67.1 ± 1.2, p = .001. Satisfaction surveys revealed that fellow perception of the curriculum was that the experience contributed to an overall improvement in their knowledge base and clinical skills while opportunity to perform transbronchial biopsies was available. CONCLUSIONS: A structured educational lung transplant curriculum was associated with improved performance on the pulmonary ITE and was perceived by fellows to be beneficial in their education and training while providing opportunities for fellows to perform transbronchial biopsies.

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.

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.

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.

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.

Lung transplantation in patients with coal workers' pneumoconiosis.

Patients with coal workers' pneumoconiosis (CWP) can develop chronic respiratory failure and require lung transplantation. A retrospective review was performed of the 712 referrals and 143 patients undergoing unilateral or bilateral lung transplantation at the University of Kentucky Medical Center between January 1999 and July 2009. Twenty-one of the 712 referrals (3%) had a diagnosis of CWP with eight patients eventually undergoing lung transplant (six single, two bilateral). The mean age of the cohort was 53 ± 5 (mean ± SD) yr (range 45-59). There was no increased risk of perioperative or postoperative complications. Six patients (75%) remain alive after a mean follow-up of 1013 ± 857 d with the two deaths attributable to sepsis 683 and 145 d after transplant, respectively. There were no pulmonary complications because of the native lung in patients after a single lung transplant, with otherwise good clinical outcomes seen after lung transplantation.

Alveolar epithelial cells express mesenchymal proteins in patients with idiopathic pulmonary fibrosis.

Prior work has shown that transforming growth factor-ß (TGF-ß) can mediate transition of alveolar type II cells into mesenchymal cells in mice. Evidence this occurs in humans is limited to immunohistochemical studies colocalizing epithelial and mesenchymal proteins in sections of fibrotic lungs. To acquire further evidence that epithelial-to-mesenchymal transition occurs in the lungs of patients with idiopathic pulmonary fibrosis (IPF), we studied alveolar type II cells isolated from fibrotic and normal human lung. Unlike normal type II cells, type II cells isolated from the lungs of patients with IPF express higher levels of mRNA for the mesenchymal proteins type I collagen, α-smooth muscle actin (α-SMA), and calponin. When cultured on Matrigel/collagen, human alveolar type II cells maintain a cellular morphology consistent with epithelial cells and expression of surfactant protein C (SPC) and E-cadherin. In contrast, when cultured on fibronectin, the human type II cells flatten, spread, lose expression of pro- SPC, and increase expression of vimentin, N-cadherin, and α-SMA; markers of mesenchymal cells. Addition of a TGF-ß receptor kinase inhibitor (SB431542) to cells cultured on fibronectin inhibited vimentin expression and maintained pro-SPC expression, indicating persistence of an epithelial phenotype. These data suggest that alveolar type II cells can acquire features of mesenchymal cells in IPF lungs and that TGF-ß can mediate this process.

Rhodococcus equi infection after lung transplantation.

Rhodococcus equi is an emerging opportunistic pathogen in immunocompromised patients. A lung-transplant recipient developed weight loss, nonproductive cough, dyspnea, and somnolence. Computed tomogram showed a pulmonary nodule and pleural changes in the right allograft that was due to R. equi infection. Alteration of cell-mediated immunity is a predisposing risk factor for R. equi infection in humans. Our patient developed R. equi infection soon after a course of high-dose corticosteroids for acute allograft infection and animal exposure. A course of intravenous vancomycin followed by single-agent long-term therapy with oral ciprofloxacin was successful.