Objectives: Heart transplant is the only definitive treatment of end-stage heart failure. Venoarterial extracorporeal membrane oxygenation may be used as a bridge to heart transplant. This technique may be used after heart transplant for conditions refractory to medical treatment like primary graft failure. Previously, we reported our experience with patients who received extracorporeal support as a bridge to emergency heart transplant. In this study, we present our perioperative experience with heart transplants in which extracorporeal support was used.
Materials and Methods: We retrospectively screened the data of 31 patients who were seen at our center between January 2014 and June 2016. We screened for patients who were admitted to the intensive care unit before transplant and who required venoarterial extracorporeal membrane oxygenation for circulatory support and postoperative patients who required extracorporeal support. Patient demographics and characteristics, clinical data, and extracorporeal support data were collected from our electronic database and patient medical records.
Results: There were 14 patients who required perioperative extracorporeal support. Preoperative support was performed in 3 patients before transplant, and postoperative support was performed in 11 patients after transplant. The mean age was 37.7 years in patients within the preoperative group and 29.7 years in patients within the postoperative group. One patient with preoperative support and 5 with postoperative support were pediatric patients. The main indication for transplant was dilated cardiomyopathy in both groups (100% and 63.7%). Overall mortality rates were 33% in the preoperative group and 63.7% in the postoperative group.
Conclusions: For patients on heart transplant wait lists who are worsening despite optimal medical therapy, venoarterial extracorporeal membrane oxygenation support is a safe and viable last resort. In addition, extracorporeal support can be used during the posttransplant period as salvage therapy in heart recipients with hemodynamic deterioration. In our experience, preoperative extracorporeal support had lower mortality rates compared with postoperative support.
Key words : Cardiac failure, Extracorporeal assist, Preoperative, Postoperative
Heart transplant is the only definitive treatment for end-stage heart failure in adult and pediatric patients.1-3 Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is one of several mechanical circulatory support devices used for patients with refractory cardiac failure (RCF).1 Venoarterial extracorporeal membrane oxygenation may be used as a bridge to heart transplant in adult and pediatric patients.2,3 This technique is increasingly used as a short-term circulatory support in patients with RCF, providing a bridge to heart transplant.4 Venoarterial extracorporeal membrane oxygenation may be used after heart transplant for conditions refractory to medical treatment like primary graft failure.5 Previously, we reported our experience with patients who received VA-ECMO as a bridge to emergency heart transplant in the intensive care unit (ICU).6 In this study, we present our perioperative experience with heart transplant recipients in which VA-ECMO was performed in our ICU.
Materials and Methods
We retrospectively screened the data of 31 heart transplants performed between January 2014 and June 2016 at our center. Patients who were admitted to the ICU before transplant and who did not respond to optimal medical therapy and required VA-ECMO for circulatory support and patients who required postoperative VA-ECMO support were included in our study. There were 14 patients who had perioperative VA-ECMO support during our study period. Patients were divided into 2 groups, with 3 patients requiring preoperative extracorporeal support before transplant and 11 patients requiring postoperative extracorporeal support after transplant.
Patient demographics and characteristics, clinical data, and extracorporeal support data were collected from our electronic database and patient medical records. Patient demographics and characteristics included age, sex, body weight, height, preoperative diagnosis, ICU mortality, hospital mortality, overall mortality, and heart transplant operation time. Clinical data collected were requirement for invasive mechanical ventilation, duration of mechanical ventilation before and after transplant, requirement for tracheotomy, presence of cardiac arrest, use of left ventricular assist device (LVAD) as a bridge to heart transplant, infectious complications, and major echocardiographic measurements. The extracorporeal support data that we included were duration of ECMO support, time between ECMO and heart transplant for preoperative cases, and time between heart transplant and ECMO for postoperative cases, ECMO type (peripheral or central), presence of complications like bleeding, leg ischemia, and ulceration, technical complications, and requirement for pump and cannula change.
Life-sustaining treatments were instituted at the discretion of the attending physicians. Criteria for extracorporeal support and weaning were determined at the discretion of the attending physicians.
The study protocol complied with the Helsinki Declaration of 1975. This study was approved by Baskent University Institutional Review Board (project number KA 16/327) and was supported by the Baskent University Research Fund.
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 20.0, IBM Corporation, Armonk, NY, USA). All results are expressed as means ± SD or as number and percentage.
From January 2014 to June 2016, a total of 31 heart transplants were performed at Baskent University Hospital in Ankara, Turkey. Patients who had no requirement for VA-ECMO support during the perioperative period (n = 17) were excluded. Of the 31 patients, the medical records of 14 heart transplant recipients (45.2%) were retrospectively evaluated. Preoperative VA-ECMO support was performed in 3 patients (21.4%) as a bridge to emergency heart transplant. Postoperative VA-ECMO support was performed in 11 patients after heart transplant. In the postoperative group, the main indication for VA-ECMO support was graft failure.
The main patient demographics and characteristics are presented in Table 1. The mean age was 37.7 years (range, 12-51 y) in patients in the preoperative group and 29.7 years (range, 8-59 y) in the postoperative group. One patient in the preoperative group and 5 in the postoperative group were pediatric patients (under 18 y), and 33.3% of the preoperative group and 45.5% of the postoperative group were female patients. The main indication for heart transplant was dilated cardiomyopathy in both groups (100% and 63.7%). There was no incidence of ICU and hospital mortality in the preoperative group. However, 1 patient died 29 days after transplant at home. In the postoperative support group, 5 patients died in the ICU and 1 patient died in the hospital ward. Overall mortality rates were 33% in the preoperative support group and 63.7% in the postoperative support group. The mean operation time for heart transplant was 7.7 hours in the preoperative and 8.6 hours in the postoperative support group.
Patient clinical data are presented in Table 2. One patient in each group required mechanical ventilation before heart transplant. For these patients, duration of mechanical ventilation was 3.3 days in the preoperative and 1 day in the postoperative support group. All patients in both groups were mechanically ventilated after heart transplant. For these patients, duration of mechanical ventilation was 4 days in the preoperative and 11 days in the postoperative support group. Tracheotomy was performed in 3 patients (27.3%) in the postoperative group. One patient in the preoperative and 8 patients in the postoperative support group had cardiac arrests. We performed extracorporeal cardiopulmonary resuscitation (E-CPR) in 1 patient in each group. These 2 patients were discharged from the hospital, and they are still alive. In the postoperative group, 3 patients had LVAD as a bridge to heart transplant.
The rates of major infectious complications with culture confirmation are presented in Table 2. Blood and catheter-related infections were observed in 2 patients from the preoperative group and in 4 patients from the postoperative group. Transthoracic echocardiographic measurements are presented in Table 2. Ejection fraction values of patients after heart transplant were improved in both groups.
The extracorporeal support data are presented in Table 3. Duration of ECMO support was 13.3 days in the preoperative group and 8.1 days in the postoperative group. Initiation of ECMO support was 13.3 days before transplant in the preoperative group. Initiation of ECMO support was 16.8 days after transplant in the postoperative group. Most patients had peripheral VA-ECMO in the preoperative group (100%) and postoperative group (54.6%). Peripheral ECMO was converted to central ECMO for 1 patient in each group.
Venoarterial extracorporeal membrane oxygenation complications are presented in Table 3. An ECMO pump was changed in 1 patient from the preoperative group and in 3 patients from the postoperative group. An ECMO cannula was changed in 1 patient from the preoperative group and in 4 patients from the postoperative group. One patient in the preoperative support group required percutaneous balloon atrial septostomy for left ventricle venting.
In this study, we present our experiences with 14 heart transplant recipients who received VA-ECMO during the perioperative period by the same anesthesia and intensive care team of ours in the ICU. Three patients required preoperative extracorporeal support. All patients were on the wait list of the National Organ Procurement Organization Registry as candidates for emergency heart transplant after VA-ECMO support. All peripheral VA-ECMOs were done with percutaneous cannulation using ultrasonography guidance.
In the preoperative group, VA-ECMO was performed under analgesia and sedation with local anesthesia. One patient was intubated during the procedure because of cardiac arrest. One patient required conversion of peripheral to central extracorporeal support, with this procedure performed in the operating room. All of the patients who required preoperative VA-ECMO were discharged from the hospital with no major complications. One patient died 29 days after discharge at home. Thus, the preoperative group had an overall mortality rate of 33.3%, with 2 patients still alive and periodically supervised by our center.
Eleven patients required postoperative extracorporeal support after heart transplant, with most receiving peripheral VA-ECMO support using femoral vessels in the ICU. Four of these patients required central extracorporeal support during heart transplant. All patients in the postoperative group were intubated and mechanically ventilated during the procedure. One patient required conversion of peripheral to central extracorporeal support, with this procedure also performed in the operating room. Of the 11 patients in the postoperative support group, 5 died during the ICU stay and 1 patient died in the hospital ward. Another patient died after discharge at home. Thus, the postoperative group had an overall mortality rate of 63.6%, with 4 patients still alive and periodically supervised by our center.
Venoarterial extracorporeal membrane oxygenation is used in RCF patients as a bridge to decision, a bridge to candidacy, and a bridge to heart transplant. Its routine use for urgent heart transplant is not widely accepted in most centers because of the limited duration for this support.7 In some European countries including our country and the United States, a heart allocation system provides priority status granted to the sickest patients.2,6 Patients in our preoperative group were admitted to the ICU for medical treatment of RCF. They were not on the national wait list. They showed no improvement despite optimal medical therapy. Our team decided to perform VA-ECMO as a salvage therapy due to RCF treatment. We enrolled preoperative patients to the national heart allocation system after VA-ECMO support and considered these patients as urgent candidates for heart transplant, giving them high priority. Finally, all 3 of these patients had successful heart transplant procedures.
Cardiothoracic surgeons have traditionally performed ECMO cannulation with open access in the operating room. Recently, anesthesiologists and intensivists have performed cannulation by a percutaneous approach guided with ultrasonography in the ICU. The most preferred cannulation site is the femoral vessel.6,8 The use of emergent venoarterial extracorporeal life support using femoral veins for cannulation has been reported in a large patient series, with the authors stating that femoral cannulation provided reliable access in urgent conditions.7 The femoral route was used in our patients for VA-ECMO support at the bedside in both the preoperative and most of the postoperative group patients. Barth and associates used peripheral VA-ECMO support as a bridge to urgent heart transplant. They reported on 8 of 242 patients (3.3%) who underwent urgent heart transplant and a mean duration of extracorporeal life support of 6.3 ± 4.6 days.7 We performed 31 heart transplants during the study period, with 3 patients (9.7%) undergoing urgent heart transplant. The mean duration of VA-ECMO support was 13.3 ± 11.8 days in our preoperative group patients. The difference between extracorporeal support duration can be explained by the low organ donation rates in our country.
In our study, 11 of 31 heart transplant patients (35.5%) required VA-ECMO support after transplant. The main indication for extracorporeal support was graft failure. Time interval of extracorporeal support after heart transplant was 16.8 ± 43.8 days (range,
0-140 d). The mean duration of support was 8.1 ± 6.5 days. Eight patients (72.7%) required VA-ECMO support within 48 hours postoperatively. We performed central VA-ECMO in 4 patients in the operating room. One patient required E-CPR in the ICU. Intensivists performed all peripheral ECMO cannulations. Three of our patients required late extracorporeal support. In a report from Lima and associates, 11 of 71 heart transplant recipients (15.5%) presented with primary graft dysfunction (PGD) and required central extracorporeal support. Six patients could not be weaned from cardiopulmonary bypass, 3 had severe hemodynamic instability, and 2 had cardiac arrest. The average duration of extracorporeal support was 76.4 ± 47.4 hours, with hospital mortality rate of 18.2%. The group concluded that central VA-ECMO promoted cardiac recovery within a few days in most patients.9 We performed peripheral VA-ECMO support initially in our patients in the ICU. One patient was converted later to central VA-ECMO. In addition, our hospital mortality rate was higher than that reported by Lima and associates.
Chou and associates analyzed 385 heart transplants, with 46 patients (12%) having graft failure and requiring ECMO as a rescue therapy. The mean extracorporeal support duration was 155 ± 145 hours. The overall success rate in their patients was 47.9%. They found no survival difference between early and late graft failure. They concluded that ECMO does play a role in rescue in catastrophic conditions.10 In our study, the overall mortality rate was 62.5% in our “early” and 66.6% in “late” graft failure patients. Our overall mortality rate was higher than that reported by the previous authors.
The International Society of Heart and Lung Transplantation reported a consensus conference report on PGD after heart transplant. The authors reviewed all aspects of PGD and studied the data of 42 international centers. They concluded that, if medical efforts are inadequate, mechanical support must be performed in PGD conditions. The preferences of mechanical support type have been noted as intra-aortic balloon pump, ECMO, and ventricular assist device. In addition, some high-volume centers prefer intra-aortic balloon pump as a first-line mechanical support.11 We preferred VA-ECMO as a mechanical support in cases of PGD according to our center’s protocol.
In their study of 114 consecutive heart transplant patients, Santise and associates reported that 15.7% of patients showed primary graft failure rate in which VA-ECMO support was required. In addition, 13 of 18 patients also had intra-aortic balloon pump before ECMO implantation. The remaining patients had absolute contraindication to intra-aortic balloon pump. The mean VA-ECMO support time was 6.2 ± 3.2 days. The authors concluded that a multidisciplinary (intensivists, cardiologists, and surgeons) evaluation of ECMO patients is important for high success rates.5 The mean duration of support was 8.1 ± 6.5 days in patients within the postoperative group. In our center, we also use a multidisciplinary approach over 24-hour periods for heart transplant patients.
Pediatric patients who are on heart transplant wait lists frequently require bridge to transplant with mechanical circulatory support. In an analysis of 2777 pediatric heart transplant patients, 189 patients (6.8%) had preoperative VA-ECMO support.3 One of the preoperative group patients, a 12-year-old girl, required VA-ECMO support when she underwent emergency heart transplant. Five patients (45.5%) in the postoperative group patients were also pediatric patients (under 18 y). Approximately 40% of our perioperative VA-ECMO patients were in the pediatric age range.
The ECMO circuit activates coagulation, fibrinolytic, and complement systems. Extracorporeal support has several hematologic complications, with bleeding being the most common. During treatment of anticoagulation, the risk of bleeding must be balanced with the risk of thrombosis.12 Our preoperative and postoperative group patients received anticoagulation agents with intravenous unfractionated heparin infusion. Anticoagulation administration was monitored with activated clotting time at the bedside. The targeted level of activated clotting time was 180 seconds. One patient in each group suffered from intractable bleeding from cannulation sites during extracorporeal support. We were able to treat these complications with conversion of peripheral support to central type.
Peripheral cannulation of femoral vessels especially for the arterial side is associated with increased risk of limb ischemia. This risk can be remedied with insertion of a distal perfusion or drainage cannula to provide antegrade arterial perfusion.12 In our patients with peripheral extracorporeal support, a distal perfusion cannula with anterograde route was inserted before femoral arterial ECMO cannulation. Patients were examined daily with Doppler ultrasonography for adequate arterial circulation in the arterial side. Despite these measures, 1 patient in the preoperative group and 4 patients in the postoperative group developed limb ischemia. This complication occurred in 2 patients with E-CPR.
In a large recent meta-analysis, Ouweneel and associates reported that VA-ECMO is increasingly used in patients during cardiac arrest. In cardiac arrest, the use of extracorporeal life support was associated with an increased survival rate and an increased favorable neurologic outcome.13 Lasa and associates concluded that, for children who receive in-hospital CPR for more than 10 minutes, E-CPR is associated with improved survival with favorable neurologic results compared with conventional CPR.14 Despite better prognosis with VA-ECMO, there have been few reports regarding urgent heart transplant after E-CPR.6,12 We used VA-ECMO support during CPR for 1 of our pediatric patients who was hospitalized for medical treatment of RCF; this patient underwent emergency heart transplant after 22 days. She was discharged from the hospital with no neurologic sequel. Among our postoperative group patients, a 17-year-old girl had a cardiac arrest 6 hours after transplant. We performed VA-ECMO, and she was discharged from the hospital with no neurologic sequel.
The discrepancy between the limited availability of donor hearts and the increasing number of candidates whose condition deteriorates while on wait lists has led to an increasing use of LVADs as a bridge to heart transplant. Thus, the use of LVADs as a bridge to transplant has evolved to become the standard of care in most centers.15 There were no patients with LVADs as a bridge to transplant in our preoperative group. Three patients in the postoperative group had LVADs before transplant. Only 1 of these was discharged from the hospital after heart transplant.
Left ventricular distension during VA-ECMO can result in impaired ventricular recovery or worsening of injury. To evaluate adequate left ventricular decompression, daily echocardiographic examinations can be helpful.12 When pharmacologic measures are not able to provide adequate decompression, some mechanical techniques like left ventricular venting, atrial septostomy, and additional mechanical support devices can be considered.8,12 Percutaneous balloon atrial septostomy may be a safe and efficient strategy for discharging the left atrium in both adults and children supported by VA-ECMO.16 One adult patient in the preoperative group had left ventricular distention during extracorporeal support. This complication was treated by balloon atrial septostomy at the coronary angiography unit.
Temporary or short-term mechanical circulatory support before heart transplant as a preoperative bridging has been reported to have comparable or good postoperative outcomes compared with VA-ECMO.17,18 We have limited experience regarding VA-ECMO support for bridge to urgent heart transplant. However, our patients were successfully transplanted after support with VA-ECMO.6 The use of VA-ECMO during both the early and late postoperative periods for severe PGD in heart transplant recipients is a widely accepted multidisciplinary treatment.5,11 However, we used postoperative extracorporeal support in our patients. We have limited experience regarding VA-ECMO support for PGD in heart transplant recipients.
There are some limitations of this study. First, the study design is retrospective and has a small population size. Second, the clinical conditions of the preoperative and postoperative patients were different. Third, pediatric and adult patients are presented together. Fourth, intergroup analysis was not performed. Despite these limitations, we present our limited experience on perioperative VA-ECMO support among heart transplant recipients.
In conclusion, for patients on heart transplant wait lists who are worsening despite optimal medical therapy, VA-ECMO support is a safe and viable last resort. In addition, VA-ECMO support can be used during the postoperative period of heart transplant recipients with hemodynamic deterioration as salvage therapy. In our experience, preoperative VA-ECMO support had a lower mortality rate compared with postoperative support.
Volume : 15
Issue : 1
Pages : 224 - 230
DOI : 10.6002/ect.mesot2016.P100
From the 1Department of Anesthesiology and Critical Care Medicine and the 2Department of Cardiovascular Surgery, Faculty of Medicine, Baskent University, Ankara, Turkey
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Ender Gedik, Baskent University Faculty of Medicine, Department of Anesthesiology and Critical Care Medicine, 06490 Ankara, Turkey
Phone: +90 312 203 6868 (extension 4841)
Table 1. Patient Demographics and Characteristics
Table 2. Patient Clinical Data
Table 3. Extracorporeal Support Data