Andre Simon

Proof of concept: hemodynamic response to long-term partial ventricular support with the synergy pocket micro-pump

OBJECTIVES The purpose of this study was to test the hemodynamic effects of partial ventricular support in patients with advanced heart failure. BACKGROUND The use of current left ventricular assist devices (VADs) that provide full circulatory support is restricted to critically ill patients because of associated risks. Smaller, less-invasive devices could expand VAD use to a larger pool of less-sick patients but would pump less blood, providing only partial support. METHODS The Synergy Pocket Micro-pump device (CircuLite, Inc., Saddle Brook, New Jersey) pumps approximately 3.0 l/min, is implanted (off pump) via a mini-thoracotomy, and is positioned in a right subclavicular subcutaneous pocket (like a pacemaker). The inflow cannula inserts into the left atrium; the outflow graft connects to the right subclavian artery. RESULTS A total of 17 patients (14 men), age 53 +/- 9 years with ejection fraction 21 +/- 6%, mean arterial pressure 73 +/- 7 mm Hg, pulmonary capillary wedge pressure 29 +/- 6 mm Hg, and cardiac index 1.9 +/- 0.4 l/min/m(2) received an implant. Duration of support ranged from 6 to 213 (median 81) days. In addition to demonstration of significant acute hemodynamic improvements in the first day of support, 9 patients underwent follow-up right heart catheterization at 10.6 +/- 6 weeks. These patients showed significant increases in arterial pressure (67 +/- 8 mm Hg vs. 80 +/- 9 mm Hg, p = 0.01) and cardiac index (2.0 +/- 0.4 l/min/m(2) vs. 2.8 +/- 0.6 l/min/m(2), p = 0.01) with large reductions in pulmonary capillary wedge pressure (30 +/- 5 mm Hg vs. 18 +/- 5 mm Hg, p = 0.001). CONCLUSIONS Partial support appears to interrupt the progressive hemodynamic deterioration typical of late-stage heart failure. If proven safe and durable, this device could be used in a relatively large population of patients with severe heart failure who are not sick enough to justify use of currently available full support VADs. (Safety and Performance Evaluation of CircuLite Synergy; NCT00878527).

Extracorporeal Membrane Oxygenation in Nonintubated Patients as Bridge to Lung Transplantation

We report on the use of veno‐arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18–35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.

Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation.

Background. Bronchiolitis obliterans syndrome (BOS) is a major cause of morbidity and mortality after lung transplantation (LTx). Macrolides are a promising treatment option for BOS. The objective of this study was to determine long-term results of azithromycin treatment in patients with BOS. Variables to predict treatment response were evaluated. Methods. An observational study in a single center was performed. Eighty-one adult LTx-recipients (single, double, combined, and re-do) with at least BOS stage 0p (mean forced expired volume in 1 second [FEV1] 55±19%) were included. For treatment, 250 mg of oral azithromycin was administered three times per week. Results. Twenty-four of 81 (30%) patients showed improvement in FEV1 after 6 months, 22/24 already after 3 months of treatment. By univariate analysis, responders at 6 months had higher pretreatment bronchoalveolar lavage (BAL) neutrophils (51±29 vs. 21±24%). A cutoff value of <20% in pretreatment BAL had a negative predictive value of 0.91 for treatment response. Thirty-three patients (40%) showed disease progression during follow-up (491±165 days). Cox regression analysis identified a rapid pretreatment decline in FEV1 and comedication of an mammalian target of rapamycin inhibitor as positive predictors and proton pump inhibitor comedication and a treatment response at 3 months as negative predictors for disease progression (FEV1 <90% baseline). Conclusions. Azithromycin can improve airflow limitation in a significant proportion of patients with even long-standing BOS. The majority of responders were identified after 3 months of treatment. Results indicate the predictive value of BAL neutrophilia for treatment response and pretreatment course of FEV1 as a variable for disease progression. Beneficial effects on gastroesophageal reflux disease may be a mechanism of action.

Bridge to Thoracic Organ Transplantation in Patients with Pulmonary Arterial Hypertension Using a Pumpless Lung Assist Device

We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end‐stage pulmonary hypertension (PH) including patients with veno‐occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy‐like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart–lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low‐resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required.

Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV)

Abstract: The potential risk of viral transmission in the setting of xenotransplantation has gained major attention. Different porcine cell types have been shown to release retroviral particles, which are infectious for human cell lines in vitro. However, there are only a few data on whether PERV (pig endogenous retrovirus) is able to infect primary human cells. In this study we have analyzed endothelial cells, vascular fibroblasts, mesangial cells, mononuclear cells, hematopoetic stem cells and bone marrow stromal cells for PERV transmission. We now provide evidence for primary human endothelial cells, vascular fibroblasts, and mesangial cells to be susceptible to PERV transmission. PERV infection was productive in endothelial cells and mesangial cells. Our data confirm and extend former reports concerning the PERV infection of human cells. The PERV infection of different primary human cells represents further significant evidence for a viral risk during xenotransplantation. In this context, special attention should be directed towards productive infection of human endothelial cells: in the setting of xenotransplantation this cell type will have close contact with porcine cells and PERV particles.

Methylene blue: The drug of choice for catecholamine- refractory vasoplegia after cardiopulmonary bypass?

OBJECTIVES Vasoplegia is a frequent complication after cardiopulmonary bypass that often requires the application of norepinephrine. In a number of cases, however, vasoplegia is refractory to norepinephrine. The guanylate cyclase inhibitor methylene blue could be an attractive treatment alternative in such cases. This study examines the results of methylene blue therapy for norepinephrine-refractory vasoplegia after cardiopulmonary bypass. METHODS A total of 54 patients with norepinephrine-refractory vasoplegia after cardiopulmonary bypass were treated with methylene blue (2 mg/kg) administered intravenously through a period of 20 minutes. The effects on hemodynamics, norepinephrine dosage, and clinical outcome were evaluated. RESULTS Three patients (5.6%) died during the hospital stay. A clinically relevant increase in systemic vascular resistance and a decrease in norepinephrine dosage were observed in 51 patients within 1 hour after methylene blue infusion. Four patients (7.4%) had no response to methylene blue. No adverse effects related to methylene blue were observed. CONCLUSIONS A single dose of methylene blue seems to be a potent approach to norepinephrine-refractory vasoplegia after cardiopulmonary bypass for most patients, with no obvious side effects. Guanylate cyclase inhibitors could be a novel class of agents for the treatment of norepinephrine-refractory vasoplegia after cardiopulmonary bypass. A controlled clinical trial is now needed to evaluate the role of methylene blue in this situation.

Community-acquired respiratory viral infections in lung transplant recipients: a single season cohort study.

Background. The impact of community-acquired respiratory virus (CARV) infections on bronchiolitis obliterans syndrome (BOS) and outcome after lung transplantation (LTx) and diagnostic techniques were prospectively evaluated. Methods. A single-center prospective cohort study was performed in LTx-outpatients between October 31, 2005 and April 30, 2006. Symptoms of respiratory tract infections were recorded and nasopharyngeal and oropharyngeal swabs were obtained. Lower respiratory sampling was performed when indicated. Immunofluorescence testing, cultures, and polymerase chain reaction for 12 different CARV were applied. Patients were followed up until December 31, 2007. New onset and BOS-stage was recorded 1 year after presentation. Results. Three hundred eighty-eight LTx-recipients were screened. Fifty-one percent reported of symptoms of respiratory tract infection. Seven hundred seventy upper and 180 lower respiratory samples were obtained. Thirty-four CARV were detected in 30 patients (7.7%): 12 parainfluenza, 7 respiratory syncytial virus, 6 metapneumovirus, 5 coronavirus, 3 rhinovirus, and 1 influenza virus. At 1 year, 43 new cases of BOS developed. One-year incidence of BOS was 25.0% in CARV-positive versus 9.0% in CARV-negative patients (log-rank P=0.01). Symptomatic CARV-infection proved to be a significant covariate for 1-year BOS-free survival in multivariate analysis (P=0.002, adjusted hazard ratio 4.13). CARV-infection did not influence BOS progression in 88 patients with prior BOS (P 0.45). After paramyxovirus infection, 8 of 24 patients developed new-onset BOS, whereas no case was recorded after rhinovirus and coronavirus infection. Discussion. Surveillance detected CARV in LTx outpatients infrequently. Symptomatic CARV-infection increases the risk for new onset of BOS, but not progression. Risk to develop BOS was especially increased after paramyxovirus infection.

Indications for and outcomes after combined lung and liver transplantation: a single-center experience on 13 consecutive cases.

Background. Combined lung and liver transplantation (Lu-LTx) is a therapeutic option for selected patients with coexisting lung and liver disease. For several reasons, Lu-LTx is performed in few centers and information about the technical issues, posttransplant management and long-term outcomes associated with this procedure is limited. Methods. We analyzed data from 13 consecutive patients who underwent combined Lu-LTx at Hannover Medical School (Hannover, Germany) between April 1999 and December 2003. The main indications were cystic fibrosis, &agr;1-proteinase inhibitor deficiency and portopulmonary hypertension. All patients had advanced cirrhosis and severe pulmonary disease manifestation. Results. Ten patients received a sequential double Lu-LTx, one patient received a single Lu-LTx, one received a double lung and split liver transplantation, and one received an en-bloc heart-lung and liver translantation. Immunosuppression was based on cyclosporine in a triple/quadruple regimen. Postoperative surgical complications occurred in eight patients. There were two perioperative deaths; two patients died during the first year on day 67 and 354, respectively, and one patient died at month 53. The overall patient survival rates at 1, 3, and 5 years were 69%, 62%, and 49%, respectively. Conclusion. Combined Lu-LTx is a therapeutic option for highly selected patients with end-stage lung and liver disease with acceptable long-term outcome.

Comparison of inhaled iloprost and nitric oxide in patients with pulmonary hypertension during weaning from cardiopulmonary bypass in cardiac surgery: a prospective randomized trial.

OBJECTIVE The objective of this study was to compare the efficacy of inhaled iloprost and nitric oxide (iNO) in reducing pulmonary hypertension (PHT) during cardiac surgery immediately after weaning from cardiopulmonary bypass (CPB). DESIGN A prospective randomized study. SETTING A single-center university hospital. PARTICIPANTS Forty-six patients with PHT (mean pulmonary artery pressure (mPAP) > or = 26 mmHg preoperatively at rest, after anesthesia induction, and at the end of CPB) scheduled to undergo cardiac surgery were enrolled. INTERVENTIONS Patients were randomly allocated to receive iloprost (group A, n = 23) or iNO (group B, n = 23) during weaning from CPB. MEASUREMENTS AND MAIN RESULTS Heart rate, mean arterial pressure, central venous pressure, pulmonary artery pressure (PAP), pulmonary capillary wedge pressure, and left atrial pressure were recorded continuously. Iloprost and iNO were administered immediately after the end of CPB before heparin reversal. Both substances caused significant reductions in mean PAP (mPAP) and pulmonary vascular resistance (PVR) and significant increases in cardiac output 30 minutes after administration (p < 0.0001). However, in a direct comparison, iloprost caused significantly greater reductions in PVR (p = 0.013) and mPAP (p = 0.0006) and a significantly greater increase in cardiac output (p = 0.002) compared with iNO. CONCLUSIONS PHT after weaning from CPB was significantly reduced by the selective pulmonary vasodilators iNO and iloprost. However, in a direct comparison of the 2 substances, iloprost was found to be significantly more effective.

Impact of graft colonization with gram-negative bacteria after lung transplantation on the development of bronchiolitis obliterans syndrome in recipients with cystic fibrosis

Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients frequently show airway colonization with gram-negative bacteria (GNB) both before and after LTx. Graft colonization with GNB and its relevance towards BOS development were investigated in a CF population after LTx. Adult CF patients receiving LTx and surviving at least 6 months were included in this prospective observational study between 1/1/2002 and 30/6/2006 in a single center and followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were compared for the presence of identical GNB. BOS-free survival was compared in colonized and non-colonized patients. Fifty-nine adult CF patients with a median age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966 (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB in lower respiratory tract samples. A further 18 patients (34%) demonstrated transient colonization. Thirty-four recipients had further positive samples after LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after LTx. Freedom of graft colonization with pseudomonads was independently associated with less frequent development of BOS (p=0.006). Persistent graft colonization with pseudomonads increases the prevalence of BOS after LTx in CF patients. A significant proportion of post-LTx CF patients demonstrates subsequent GNB eradication during later follow-up and this may have a protective role against development of BOS. Strategies to eradicate airway colonization or reduce bacterial load may prevent BOS in CF patients after LTx.