Heart, Lung and Circulation (2015) 24, 1239–1240 1443-9506/04/$36.00 http://dx.doi.org/10.1016/j.hlc.2015.05.006
LETTER TO THE EDITOR
Response to ‘Ex-vivo Donor Heart Perfusion: Testing the Limits of Cardiac Resilience’ We have read with interest the commentary by Dhital et al. which refers to our case report entitled ‘Successful Heart Transplant after Ten Hours Out-of-Body-time using the TransMedics Organ Care System’. As the authors of this commentary are all reasonably well published, we are certain they understand that a case report is subject to certain limits related to word counts and depth of information provided. The purpose of our case report was not provide a detailed discussion as to the mechanics of this technology but to highlight the potential use of the Organ Care System (OCS). The comments regarding the workload of the heart on the OCS are accurate. On the OCS, the heart is placed on the rig by cannulation of the ascending aorta, where oxygenated and nutrient-rich donor blood perfuses the aortic root. A cannula is inserted into the pulmonary artery where some right ventricular work can expel blood into the reservoir. The reservoir itself drains blood under gravity alone as it sits at the base of the chamber. All chambers of the heart can vent passively into the chamber, thus avoiding distending the heart. The explanation as to the intricacies of the system was beyond the scope of our case report and was not included, on advice provided at peer review. Serum lactate measurement is performed regularly throughout the donor run. A sample is taken from the system before placing the donor heart on the system that samples the donor blood. Thereafter, samples are performed when the heart is first re-animated, a minimum of two times in the first hour and a minimum of hourly following this. The ideal clinical scenario is that given in the commentary — that is, a serum lactate less than 5mmol/L and presence of an arterio-venous differential. The AV differential is a marker of consumption of lactate by the heart as an energy substrate, signifying that the heart is intact at a cellular level. It is interesting the commentary’s authors remark that they feel trends may end up being more clinically significant; we note, in particular, their ongoing work in this area and will read their articles, currently in press, with interest when they are available.
Word limits precluded the provision of detail as to the reason for the recipient’s urgent listing and the retrieval. We welcome the opportunity to provide further information: our recipient was listed urgently due to ongoing ventricular tachycardia. This resulted in recurrent firing of his AICD and was recalcitrant to medical therapy. During some of these episodes, the LVAD flows were compromised. This prompted a listing for an urgent transplant. There was no evidence of mechanical pump failure, thrombosis or sepsis at the time of listing or at explant. The actual flight time was longer than originally anticipated — just under six hours — owing to strong headwinds often faced in flights over Western Australia. This is exactly the kind of time-problem that would normally preclude the use of a heart from this donor centre. What was not mentioned in our case report was that the retrieval time was subject to a number of unforeseeable delays. These included failure of the infusion pump on the OCS, so that we had to rig a borrowed infusion pump from the donor hospital to enable provision of our maintenance solution. While the run was indeed successful and well-planned, such unforeseeable difficulties can make transplant retrieval a real test of the technology as well as the skill and ingenuity of the team. The time back at the home-hospital from arrest of the heart from the OCS and completion of transplant was 62 minutes. This is not unreasonable and does not at all constitute a prolonged wait from arrival to completion of the surgery; in fact, this is quite a short implant time. The recipient had undergone redo sternotomy and LVAD explant with excellent haemostasis and haemodynamics in a timely fashion. Cardiac function remained visibly acceptable for most of the run, until the last hour. It is generally considered unreasonable to publish the large amount of biochemical and haemodynamic data generated from a ten-hour retrieval, including an eight-hour OCS run, in a case-report. However, there were some unexpected biochemical trends during the run and, at the time of the retrieval, we sought advice from
© 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
1240
clinicians and technicians in the USA from TransMedics — while in-flight. The trends we saw were a static lactate at the end of the fifth hour, and a rising sodium and hyperglycaemia. The hyperglycaemia was present in the donor blood prior to placing the heart on the rig (glucose 10mmol/L). The sodium became high at 2 hours and 17 minutes into the retrieval; this decreased for the remainder of the run but remained above normal. After the fifth hour, lactate remained static at approximately 1.5mmol/L, with the AV differential intact. The lactate never rose above 3.5mmol/L for the entire run. Other haemodynamic points of interest included a rise in coronary blood flow to a high normal level of 90 mmHg despite stable pump flow. This necessitated a steady increase in the rate of the maintenance solution, which contains adenosine as a coronary vasodilator. Despite all of these anomalies and visual deterioration of the heart, it was thought reasonable to proceed with transplantation of the organ. The ‘oedematous’ nature of the heart is interesting and unusual. In our experience at that time, previous transplants performed with the OCS remarked on oedema as an unusual finding on endomyocardial biopsy. Oedema has occurred in shorter OCS runs, without the presence of macroscopic changes. It is also not a common finding of hearts preserved with traditional cold organ preservation. We believe that due diligence was indeed used and that the patient and the probability of a good outcome were not placed at unnecessary risk. The outcome has, indeed, been good for the patient and as the commentary acknowledges,
N.L. Stamp, R.I. Larbalestier
the period of support of ECMO is actually quite short, even by conventional expectations in primary graft dysfunction. The advent of OCS technology is a very exciting time for solid organ transplantation. The appeal for our unit was two-fold. The OCS may allow the option of assessment and reconditioning of marginal organs. Additionally, for a geographically isolated unit such as ours, the ability to extend ischaemic times is very exciting. As discussed in our case report, this heart may have been declined on the basis of prolonged ischaemic time. The OCS afforded us the ability to use the organ for a very unwell patient, who has gone on to recover extremely well, returning to pre-morbid activities. It is prudent to remember that all parties will advance scientific understanding of organ preservation and that the sharing of all information will enrich our collective knowledge and provide further questions to be answered. We look forward to these advances in knowledge and hopefully those advances will translate to remarkable outcomes, such as this one. N.L. Stamp, FRACS Westmead Hopsital, Westmead, NSW, Australia R.I. Larbalestier, FRACS Mount Medical Centre, Royal Perth Hospital, West Perth, WA, Australia Received 2 May 2015; accepted 23 May 2015; online published-ahead-of-print 9 June 2015
LETTER TO THE EDITOR
Response to ‘Ex-vivo Donor Heart Perfusion: Testing the Limits of Cardiac Resilience’ We have read with interest the commentary by Dhital et al. which refers to our case report entitled ‘Successful Heart Transplant after Ten Hours Out-of-Body-time using the TransMedics Organ Care System’. As the authors of this commentary are all reasonably well published, we are certain they understand that a case report is subject to certain limits related to word counts and depth of information provided. The purpose of our case report was not provide a detailed discussion as to the mechanics of this technology but to highlight the potential use of the Organ Care System (OCS). The comments regarding the workload of the heart on the OCS are accurate. On the OCS, the heart is placed on the rig by cannulation of the ascending aorta, where oxygenated and nutrient-rich donor blood perfuses the aortic root. A cannula is inserted into the pulmonary artery where some right ventricular work can expel blood into the reservoir. The reservoir itself drains blood under gravity alone as it sits at the base of the chamber. All chambers of the heart can vent passively into the chamber, thus avoiding distending the heart. The explanation as to the intricacies of the system was beyond the scope of our case report and was not included, on advice provided at peer review. Serum lactate measurement is performed regularly throughout the donor run. A sample is taken from the system before placing the donor heart on the system that samples the donor blood. Thereafter, samples are performed when the heart is first re-animated, a minimum of two times in the first hour and a minimum of hourly following this. The ideal clinical scenario is that given in the commentary — that is, a serum lactate less than 5mmol/L and presence of an arterio-venous differential. The AV differential is a marker of consumption of lactate by the heart as an energy substrate, signifying that the heart is intact at a cellular level. It is interesting the commentary’s authors remark that they feel trends may end up being more clinically significant; we note, in particular, their ongoing work in this area and will read their articles, currently in press, with interest when they are available.
Word limits precluded the provision of detail as to the reason for the recipient’s urgent listing and the retrieval. We welcome the opportunity to provide further information: our recipient was listed urgently due to ongoing ventricular tachycardia. This resulted in recurrent firing of his AICD and was recalcitrant to medical therapy. During some of these episodes, the LVAD flows were compromised. This prompted a listing for an urgent transplant. There was no evidence of mechanical pump failure, thrombosis or sepsis at the time of listing or at explant. The actual flight time was longer than originally anticipated — just under six hours — owing to strong headwinds often faced in flights over Western Australia. This is exactly the kind of time-problem that would normally preclude the use of a heart from this donor centre. What was not mentioned in our case report was that the retrieval time was subject to a number of unforeseeable delays. These included failure of the infusion pump on the OCS, so that we had to rig a borrowed infusion pump from the donor hospital to enable provision of our maintenance solution. While the run was indeed successful and well-planned, such unforeseeable difficulties can make transplant retrieval a real test of the technology as well as the skill and ingenuity of the team. The time back at the home-hospital from arrest of the heart from the OCS and completion of transplant was 62 minutes. This is not unreasonable and does not at all constitute a prolonged wait from arrival to completion of the surgery; in fact, this is quite a short implant time. The recipient had undergone redo sternotomy and LVAD explant with excellent haemostasis and haemodynamics in a timely fashion. Cardiac function remained visibly acceptable for most of the run, until the last hour. It is generally considered unreasonable to publish the large amount of biochemical and haemodynamic data generated from a ten-hour retrieval, including an eight-hour OCS run, in a case-report. However, there were some unexpected biochemical trends during the run and, at the time of the retrieval, we sought advice from
© 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.
1240
clinicians and technicians in the USA from TransMedics — while in-flight. The trends we saw were a static lactate at the end of the fifth hour, and a rising sodium and hyperglycaemia. The hyperglycaemia was present in the donor blood prior to placing the heart on the rig (glucose 10mmol/L). The sodium became high at 2 hours and 17 minutes into the retrieval; this decreased for the remainder of the run but remained above normal. After the fifth hour, lactate remained static at approximately 1.5mmol/L, with the AV differential intact. The lactate never rose above 3.5mmol/L for the entire run. Other haemodynamic points of interest included a rise in coronary blood flow to a high normal level of 90 mmHg despite stable pump flow. This necessitated a steady increase in the rate of the maintenance solution, which contains adenosine as a coronary vasodilator. Despite all of these anomalies and visual deterioration of the heart, it was thought reasonable to proceed with transplantation of the organ. The ‘oedematous’ nature of the heart is interesting and unusual. In our experience at that time, previous transplants performed with the OCS remarked on oedema as an unusual finding on endomyocardial biopsy. Oedema has occurred in shorter OCS runs, without the presence of macroscopic changes. It is also not a common finding of hearts preserved with traditional cold organ preservation. We believe that due diligence was indeed used and that the patient and the probability of a good outcome were not placed at unnecessary risk. The outcome has, indeed, been good for the patient and as the commentary acknowledges,
N.L. Stamp, R.I. Larbalestier
the period of support of ECMO is actually quite short, even by conventional expectations in primary graft dysfunction. The advent of OCS technology is a very exciting time for solid organ transplantation. The appeal for our unit was two-fold. The OCS may allow the option of assessment and reconditioning of marginal organs. Additionally, for a geographically isolated unit such as ours, the ability to extend ischaemic times is very exciting. As discussed in our case report, this heart may have been declined on the basis of prolonged ischaemic time. The OCS afforded us the ability to use the organ for a very unwell patient, who has gone on to recover extremely well, returning to pre-morbid activities. It is prudent to remember that all parties will advance scientific understanding of organ preservation and that the sharing of all information will enrich our collective knowledge and provide further questions to be answered. We look forward to these advances in knowledge and hopefully those advances will translate to remarkable outcomes, such as this one. N.L. Stamp, FRACS Westmead Hopsital, Westmead, NSW, Australia R.I. Larbalestier, FRACS Mount Medical Centre, Royal Perth Hospital, West Perth, WA, Australia Received 2 May 2015; accepted 23 May 2015; online published-ahead-of-print 9 June 2015
