M. Avsar

Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients

BACKGROUND Cold flush and static cold storage is the standard preservation technique for donor lungs before transplantations. Several research groups have assessed normothermic perfusion of donor lungs but all devices investigated were non-portable. We report first-in-man experience of the portable Organ Care System (OCS) Lung device for concomitant preservation, assessment, and transport of donor lungs. METHODS Between Feb 18, and July 1, 2011, 12 patients were transplanted at two academic lung transplantation centres in Hanover, Germany and Madrid, Spain. Lungs were perfused with low-potassium dextran solution, explanted, immediately connected to the OCS Lung, perfused with Steens solution supplemented with two red-cell concentrates. We assessed donor and recipient characteristics and monitored extended criteria donor lung scores; primary graft dysfunction scores at 0, 24, 48, and 72 h; time on mechanical ventilation after surgery; length of stays in hospital and the intensive-care unit after surgery; blood gases; and survival of grafts and patients. FINDINGS Eight donors were female and four were male (mean age 44·5 years, range 14-72). Seven recipients were female and five were male (mean age 50·0 years, range 31-59). The preharvest donor ratio of partial pressure of oxyen (PaO(2)) to fractional concentration of oxygen in inspired air (F(I)O(2)) was 463·9 (SD 91·4). The final ratio of PaO(2) to F(I)O(2) measured with the OCS Lung was 471·58 (127·9). The difference between these ratios was not significant (p=0·72). All grafts and patients survived to 30 days; all recipients recovered and were discharged from hospital. INTERPRETATION Lungs can be safely preserved with the OCS Lung, resulting in complete organ use and successful transplantation in our series of high-risk recipients. In November, 2011, we began recruitment for a prospective, randomised, multicentre trial (INSPIRE) to compare preservation with OCS Lung with standard cold storage. FUNDING TransMedics and German Federal Ministry of Education and Research.

First implantation in man of a new magnetically levitated left ventricular assist device (HeartMate III).

Outcomes of heart failure patients supported by a continuous-flow left ventricular assist device (LVAD) have steadily improved during the past decade, largely due to better patient selection and management. Nevertheless, adverse events, such as bleeding, infection, stroke, and thrombus, persist and limit the overall effectiveness of this therapy. Bleeding is the most common serious adverse event that results from the extensive surgery required for implantation and blood component damage due to shear forces in the small blood flow paths of current design axialflow and centrifugal-flow pumps. Excessive bleeding results in reoperations, intensive care time, and total hospital stay, which greatly increases a patient’s exposure for infection. The current clinically used pumps create levels of shear force that can activate platelets and damage von Willebrand factor, causing a disruption in the coagulation system that can manifest as thrombosis or gastrointestinal bleeding. The HeartMate III LVAD (Thoratec Corp, Pleasanton, CA) is a new compact intrapericardial centrifugal-flow pump with a full magnetically levitated rotor (Figure 1). The design differs from currently used devices due to actively controlled rotation and levitation of the rotor allowing gaps in the blood flow that are 10 to 20 times wider, which may minimize blood component trauma and result in more stable coagulation. The HeartMate III is now under clinical investigation, and we present here a case report of the first implantation of the device to support a patient with severe heart failure. The patient is a 55-year-old man with the diagnosis of dilated cardiomyopathy and a recent history of multiple hospital admissions due to worsening heart failure symptoms. With multiple medications, the mean arterial blood pressure was 70 mm Hg, cardiac index was 2.1 liters/min/m, and the left ventricular ejection fraction was 10% to 15%. He was classified as Interagency Registry for Mechanically Assisted Circulatory Support Profile 3. After meeting the HeartMate III Conformite Europeene Mark Study inclusion criteria, the patient gave informed consent, and the implantation was performed by Dr. Schmitto and his team at Hannover Medical School, Hanover, Germany on June 25, 2014. After a median sternotomy, the pericardium was only partially opened to help protect right heart function yet allowing access to the vena cava and aorta for cardiopulmonary bypass cannulation. Once full cardiopulmonary bypass was started, the pericardium was fully opened, the heart was elevated, and the myocardium was cored with the HeartMate coring knife approximately 1 cm medial to the left ventricular apex. The sewing cuff was attached around the apical opening with 2-0 Ethibond pledgeted sutures. The inflow conduit was inserted into the left ventricle, and the device was quickly secured to the heart with a locking mechanism. The outflow graft was trimmed for length and anastomosed to the ascending aorta. The percutaneous lead (driveline) was externalized with a doubletunnel technique and exited through the right upper quadrant of the abdominal wall. Cardiopulmonary bypass lasted 59 minutes, and the total operative time was 149 minutes.

Lung transplantation for severe pulmonary hypertension--awake extracorporeal membrane oxygenation for postoperative left ventricular remodelling.

Background Bilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are more common as in BLTx for other indications. We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO). Methods In 23 BLTx for severe PH, ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group). Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for monitoring. Early extubation after transplantation was attempted under continued ECMO. Results Preoperatively, all patients had severely reduced cardiac index (mean, 2.1 L/min/m2). On postoperative day 2, reduction of ECMO flow resulted in increasing LA and decreasing systemic blood pressures. On the day of ECMO explantation (median, postoperative day 8), LV diameter had increased; LA and blood pressures remained stable. Survival rates at 3 and 12 months were 100% and 96%, respectively. Data were compared to two historic control groups of BLTx without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe PH. Conclusion Early after BLTx for severe PH, the LV may be unable to handle normalized LV preload. This can be effectively bridged with awake venoarterial ECMO.

Early donor-specific antibodies in lung transplantation: risk factors and impact on survival.

BACKGROUND The impact of early donor-specific anti-HLA antibodies (DSA) on patient and graft survival after lung transplantation remains controversial. In this study we analyzed risk factors for DSA that developed before initial hospital discharge after lung transplantation (early DSA) and compared mid-term outcomes in patients with or without DSA. METHODS Between January 2009 and August 2013, 546 patients underwent lung transplantation at our institution. One hundred (18%) patients developed early DSA (Group A) and 446 (82%) patients (Group B) did not. Patient records were retrospectively reviewed. RESULTS Retransplantation (odds ratio [OR] = 2.7, 95% confidence interval [CI] 1.1 to 6.5, p = 0.03), pre-operative HLA antibodies (OR = 2.1, 95% CI 1.2 to 3.4, p = 0.003) and primary graft dysfunction (PGD) score Grade 2 or 3 at 48 hours (OR = 2.6, 95% CI 1.5 to 4.6, p = 0.001) were associated with early DSA development. Overall, 1- and 3-year survival in Group A and B patients was 79 ± 4% vs 88 ± 2% and 57 ± 8% vs 74 ± 3%, respectively (p = 0.019). Eleven Group A (11%) and 32 Group B (7%) patients died before hospital discharge (p = 0.34). Among patients surviving beyond discharge, 1- and 3-year survival in Group A and B patients was 89 ± 4% vs 95 ± 1% and 65 ± 8% vs 80 ± 3% in Group A and B patients, respectively (p = 0.04). Multivariate analysis identified early anti-HLA Class II DSA (OR = 1.9, 95% CI 1.0 to 3.4, p = 0.04) as an independent risk factor for post-discharge mortality but not for in-hospital mortality. CONCLUSIONS Pre-operative HLA antibodies, retransplantation or post-operative PGD increase the risk of developing early DSA, which were independently associated with an increased risk for mortality.

Minimally Invasive Off-Pump Left Ventricular Assist Device Exchange: Anterolateral Thoracotomy

The new generation of left ventricular assist devices has enabled minimally invasive surgical procedures. Herein we present a novel technique of left ventricular assist device exchange through a left-sided anterolateral thoracotomy.

Minimally-invasive LVAD Implantation: State of the Art

Nowadays, the worldwide number of left ventricular assist devices (LVADs) being implanted per year is higher than the number of cardiac transplantations. The rapid developments in the field of mechanical support are characterized by continuous miniaturization and enhanced performance of the pumps, providing increased device durability and a prolonged survival of the patients. The miniaturization process enabled minimally-invasive implantation methods, which are associated with generally benefitting the overall outcome of patients. Therefore, these new implantation strategies are considered the novel state of the art in LVAD surgery. In this paper we provide a comprehensive review on the existing literature on minimally-invasive techniques with an emphasis on the different implantation approaches and their individual surgical challenges.

Reduction of Driveline Infections Through Doubled Driveline Tunneling of Left Ventricular Assist Devices

The durability of ventricular assist device (VAD) therapy improved steadily over the past years. However, driveline infections remain a challenge. To test whether an improved surgical implantation technique may lower the incidence of infections, we analyzed all patients receiving a VAD implantation in the years 2008 and 2009 (group 1) and compared them with all patients who received a VAD in 2011 (group 2) after we changed our implantation method. The new technique involves tunneling of the driveline into the fascia of the musculus rectus abdominis, resulting in a longer, intrafascial run to achieve a better resistance against ascending infections. We retrospectively analyzed 40 patients in group 1 and 41 patients in group 2. One year after implantation, the infection rate was markedly reduced (22.5% [n = 9] group 1 vs. 4.9% [n = 2] group 2, P < 0.001) by the new implantation method. There was, however, no significant improvement in overall mortality. The Cox regression model identified the implantation method as an independent risk factor for 1 year after implantation driveline infection (P < 0.05). In conclusion, the new tunneling technique marks a great leap forward in long-term VAD treatment. However, overall mortality remains high and needs further improvement.

Five-year experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: Indications and midterm results

BACKGROUND Since April 2010, extracorporeal membrane oxygenation (ECMO) has replaced cardiopulmonary bypass for intraoperative support during lung transplantation at our institution. The aim of this study was to present our 5-year experience with this technique. METHODS Records of patients who underwent transplantation between April 2010 and January 2015 were retrospectively reviewed. Patients who underwent transplantation without ECMO formed Group A. Patients in whom the indication for ECMO support was set a priori before the beginning of the operation formed Group B. The remaining patients in whom the indication for ECMO support was set during transplantation formed Group C. RESULTS Among 595 patients, 425 (71%) patients (Group A) did not require intraoperative ECMO; the remaining 170 (29%) patients did. Among these patients, 95 (56%) patients formed Group B, and the remaining 75 (44%) patients comprised Group C. Pulmonary fibrosis and pre-operative dilated or hypertrophied right ventricle emerged as risk factors for the indication of non-a priori intraoperative ECMO. Patients in Groups B and C showed a higher pre-operative risk profile and higher prevalence of post-operative complications than patients in Group A. Overall survival at 1 year was 93%, 83%, and 82% and at 4 years was 73%, 68%, and 69% in Groups A, B, and C (p = 0.11). The intraoperative use of ECMO did not emerge as a risk factor for in-hospital mortality or mortality after hospital discharge. CONCLUSIONS Intraoperative ECMO filled the gap between pre-operative and post-operative ECMO in lung transplantation. Although complications and in-hospital mortality were higher in patients who received ECMO, survival was similar among patients who underwent transplantation with or without ECMO.

Preemptive treatment with therapeutic plasma exchange and rituximab for early donor-specific antibodies after lung transplantation.

OBJECTIVE De novo donor-specific anti-human leukocyte antigen antibodies develop in a high proportion of lung transplant recipients early after lung transplantation. We recently showed that de novo donor-specific antibodies (DSA) occurrence is associated with significantly increased mortality. Here, we studied the efficacy of a preemptive treatment protocol. METHODS A retrospective observational study was conducted on all lung transplantations at Hanover Medical School between January 2009 and May 2013. RESULTS Among the 500 transplant recipients, early DSA developed in 86 (17%). Of these, 56 patients (65%; Group A) received therapeutic plasma exchange, and 30 patients (35%; Group B) did not. Among Group A patients, 51 also received rituximab. Between groups, there was no statistically significant difference in mortality, incidence of pulsed steroid therapies, rejections diagnosed by biopsy specimen, incidence of bronchitis obliterans syndrome (BOS), or infections requiring hospitalization at 1 year and 3 years. Also, there were no statistically significant differences after matching 21 Group A with 21 Group B patients through propensity score analysis. Significantly more Group A patients (65%) than Group B patients (34%) cleared DSA at hospital discharge (p = 0.01). At the last control after transplantation (median, 14 months; interquartile range, 5-24 months), 11 Group A (22%) and 9 Group B patients (33%) still showed DSA (p = 0.28). CONCLUSIONS Preemptive treatment with therapeutic plasma exchange and rituximab led to improved elimination of DSA early after lung transplantation (p = 0.01). However, spontaneous elimination in untreated Group B patients also occurred frequently. This treatment protocol was not associated with significantly improved outcome.

Minimally Invasive Ventricular Assist Device Surgery

The use of mechanical circulatory support to treat patients with congestive heart failure has grown enormously, recently surpassing the number of annual heart transplants worldwide. The current generation of left ventricular assist devices (LVADs), as compared with older devices, is characterized by improved technologies and reduced size. The result is that minimally invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Minimally invasive procedures improve surgical outcome; for example, they lower the rates of operative complications (such as bleeding or wound infection). The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most implantations in the future. In this article, we summarize and describe minimally invasive state-of-the-art implantation techniques, with a focus on the most common LVAD systems in adults.