Advanced mechanical circulatory support for post-cardiotomy cardiogenic shock: a 20-year outcome analysis in a non-transplant unit

Background Post-cardiotomy cardiogenic shock (PCCS) has an incidence of 2–6 % after routine adult cardiac surgery. 0.5–1.5 % are refractory to inotropic and intra-aortic balloon pump (IABP) support. Advanced mechanical circulatory support (AMCS) can be used to salvage carefully selected number of such patients. High costs and major complication rates have lead to centralization and limited funding for such devices in the UK. We have looked the outcomes of such devices in a non-transplant, intermediate-size adult cardiothoracic surgery unit. Methods Inclusion criteria included any adult patient who had received salvage veno-arterial extra-corporeal membrane oxygenation (V-A ECMO) or a ventricular assist device (VAD) for PCCS refractory to IABP and inotropic support following cardiac surgery from April 1995-April 2015. Results Sixteen patients met the inclusion criteria. Age range was 34–83 years (median 71). There was a male predominance of 12 (75 %). Overall, 15 (94 %) had received ECMO of which, 10 (67 %) had received central ECMO and 5 (33 %) had received peripheral ECMO. One patient (6 %) had a VAD. The most common complication was haemorrhage. Stroke, femoral artery pseudo-aneurysm, sepsis and renal failure also occurred. Thirty-day survival was 37.5 %. Survival rate to hospital discharge was 31.2 %. All survivors had NYHA class I-II at 24 months follow-up. Conclusions Our survival rate is similar to that reported in several previous studies. However, the use of AMCS for refractory PCCS is associated with serious complications. The survivors in our cohort appear to maintain an acceptable quality of life.

Refractory PCCS leads rapidly to multi-organ dysfunction and is nearly always fatal [4,[7][8][9] without the use of advanced mechanical circulatory support (AMCS). AMCS devices such as extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) have been used to salvage patients who develop refractory PCCS. Survival to hospital discharge is variable [1-3, 5, 10-12] though long term survival and reasonable functional outcome can be achieved [11,[13][14][15]. However, these devices are associated with serious complications [1,2,11,[16][17][18] and are costly [9,19,20]. The UK National Health Service's (NHS) proposal to centralise AMCS funding to a few, larger cardiothoracic units has been controversial [15]. Some argue that such a move would remove this potentially, life-saving resource from those cardiothoracic surgery departments excluded from AMCS funding [15]. This prompted us to assess the outcome of the use of AMCS in a nontransplant, intermediate-sized unit (annual workload approximately 900 to 1000 major cardiac surgical operations) in Edinburgh, UK.

Methods
We retrospectively assessed our experience with AMCS in refractory PCCS over a 20-year period. These data were collected prospectively by the Royal Infirmary of Edinburgh cardiac surgery database. Our inclusion criteria included any adult patient from April 1995 to April 2015 who had received salvage V-A ECMO or VAD for PCCS refractory to IABP and maximal inotropic support following adult cardiac surgery. We gained information regarding the patients' follow-up status from accessing the cardiology follow-up clinic letters on the TrakCare R system, which captures inpatient and out-patient clinical data.
The AMCS devices utilised by our unit in duration of the study included: The Levitronix R CentriMag II for ECMO and Medtronic Bio-Medicus R 560 for VAD support.

Results
There were 18 patients who met the inclusion criteria. We excluded two patients who had had AMCS for refractory PCCS. One patient was in the paediatric age group and had been operated on prior to relocation of paediatric cardiac surgery services to the Royal Hospital for Sick Children, Glasgow in year 2000. Another patient was excluded due to the lack of recorded clarity in the database on the type of AMCS support used, any potential complications and the short and the long-term outcome of this individual. In the remaining 16 patients the age range was 34-83 years (Median 71 years).
Most common cause of death (COD) was refractory biventricular failure (37.5 %, Fig. 2), in which group of patients, AMCS was withdrawn. One patient died due to combination of biventricular failure and haemorrhagic shock whilst on VA ECMO. Thirty-day survival was 37.5 % (Fig. 3). Our survival rate to hospital discharge was 31.2 %. Upon reviewing the consultant cardiologist follow-up clinic letters on the TrakCare R database, all survivors who were discharged home were alive at 24 months and had NYHA class I-II functional status on follow-up.
Advanced age, the emergent nature of surgery, preexisting, preoperative severe left ventricular impairment were identified as possible factors leading to an adverse outcome. These findings however are limited due to the small number of subjects and the retrospective nature of the study.
Discussion & review of the literature AMCS have been in evolution for almost 50 years. AMCS devices developed in parallel with the cardiopulmonary bypass (CPB) machine by John Gibbon in 1953 [21,22]. Soon after its inception, the CPB machine was being used to salvage patients following "failed" cardiac surgery. In 1966, Michael DeBakey used the first LVAD to support a patient who was in refractory PCCS [21]. After the first heart transplantation by Christiaan Barnard in 1967 and widespread acceptance of transplantation, AMCS devices have been regularly used to sustain those patients in refractory PCCS to allow time for decision for further management with implantable devices or heart transplantation [21].
There are two forms of ECMO; veno-venous (VV) which is usually utilized to support isolated respiratory failure and veno-arterial (VA) ECMO used to support cardiac, respiratory or mixed cardiorespiratory failure. Both types of ECMO can be applied centrally and peripherally [23,24]. There are two types of VADs. Shortterm, percutaneous VADs, which can be inserted in the catheter laboratory, serve as a temporizing measure to stabilize patients in acute cardiogenic shock. More longterm, surgically-implanted VADs are designed to increase patient's life span and/or bridge patients to transplantation [15]. VADs can be used to support the failing right ventricle, left ventricle or both. According to the UK VAD registry, scarcity of donor hearts has stimulated consideration of implantable AMCS devices for more prolonged circulatory support [20]. Recent studies have demonstrated that modern continuous flow AMCS devices such as CentriMag R pumps with magnetically levitated rotors and more effective modern oxygenators, can be more easily implanted, leading to much better survival in patients with post-cardiotomy cardiogenic shock in the recent years [25][26][27].
In our literature search we identified 15 major articles. In the largest cohort, Hernandez et al. [3] collated data from 5,735 patients who underwent salvage VAD support for refractory PCCS. They reported 54.1 % survival rate to hospital discharge. They concluded that VAD is a valuable, life-saving therapeutic manoeuvre. Rastan et al. Abbreviations: ACS acute coronary syndrome, AF atrial fibrillation, AMCS advanced mechanical circulatory support, AVR aortic valve replacement, CABG coronary artery bypass grafting surgery, CPB cardiopulmonary bypass, COD cause of death, BiVent failure biventricular failure, MVR mitral valve replacement, IE infective endocarditis, CVA cerebrovascular accident, IVC, inferior vena-cava, NYHA New York Heart Association, CTICU cardiothoracic intensive care unit, HDU high dependency unit, implantable cardioverter defibrillator, MI myocardial infarction, LVSD left ventricular systolic dysfunction, TVD triple vessel coronary artery disease, LV left ventricular, MR mitral regurgitation, PVD peripheral vascular disease, MODS multi-organ dysfunction syndrome, VF ventricular fibrillation, VAD ventricular assist device, VA veno-arterial; a All patients with renal failure required renal replacement therapy [5] performed ECMO support in 516 patients with refractory PCCS. A total of 24.8 % of patients survived to discharge to the community. However, after 5 years 13.7 % were alive and 17.4 % of patients suffered severe morbidity [5]. In another large cohort of 219 patients Doll et al. [28] reported 24.8 % survival to discharge and 16.9 % 5-year survival for their cohort of refractory PCCS patients who had received salvage ECMO support. Hsu et al [12] reported a cohort of 51 patients who had undergone cardiac surgery and suffered refractory PCCS requiring ECMO circulatory support. The 30-day, 3month and 1-year mortality rates were 49, 65 and 71 % respectively. Mehta et al. [13] reported a large cohort of 1,279 patients who had undergone VAD for circulatory support for refractory PCCS. They claimed that 584 (45.7 %) patients were successfully weaned from VAD and 323 (25.3 %) patients survived to discharge from the hospital. In a small cohort of 12 patients with refractory PCCS, DeRose et al. [2] reported that 9 patients (75 %) survived to discharge from the hospital with LVAD implantation, 8 (67 %) survived to transplantation and 1 (8 %) successfully underwent explanation of LVAD not requiring transplantation. However, they reported 42 % rate of LVAD related infective complications.
With respect to longer term outcomes; a study by Ko et al. [11] reported a cohort of 76 patients undergoing ECMO support for refractory PCCS. They reported that, although 46 patients (60.5 %) were successfully weaned from ECMO, 20 (26.3 %) survived to discharge. However all survivors were reported to be of   [17] reported refractory PCCS support with VAD with 37 % survival to hospital discharge. They reported that all survivors were "leading active lives". In 72.7 % of survivors ejection fraction had normalized on follow-up echocardiogram. AMCS devices also have disadvantages. They are currently not funded within the cardiac surgery tariff and are quite costly [9,19,20]. According to a study conducted at the University Hospital of South Manchester [9] (an NHS institution), the cost of capital equipment, device maintenance and single-use elements (e.g. tubing) of the CentriMag R device is £3542. The total per patient cost of VAD and ECMO were reported as £15 669 and £8616 respectively. However the costs associated with the device and the ICU stay may vary substantially depending on the duration of AMCS. The cost of implantable VAD per patient receiving a device is £173,841 or US$316,078. The most costly aspect is implantation of the device (£63,830, US$116,056) and the initial hospital stay in the ITU and ward totals as much as £14,500 or US$26,364 [29]. A clinical trial indicated the cost of quality adjusted life year for ECMO in the UK to be £19,252 [30]. Also there are reports [1,2,11,[16][17][18] of serious device-related complications including: bleeding, thrombus formation and embolization, cerebrovascular accidents, device infection, limb ischaemia and multi-organ dysfunction syndrome/failure. However, there is evidence that on-the-table, early implantation of AMCS devices, prior to leaving the operating theatre from the initial operation, substantially improves survival as compared to late implantation out-with the operating theatre [6,26]. Given the reported survival rates and the extent of resources involved, we recommend that each case should be assessed in its own individual merit. Involvement of a cardiac surgeon, other than the surgeon involved in the initial operation, the clinical director of the department of cardiac surgery, as well as involving the perfusionist and the on-call anaesthetist in the decision making process is imperative in gaining optimal outcomes for patients undergoing AMCS for refractory PCCS while optimising the costbenefit equation.

Conclusion
AMCS devices can be used to salvage some patients with refractory PCCS who would otherwise have not survived. However, ACMS are associated with high rates of severe, systemic and device-related complications as well being costly. We recommend team approach to decision-making and early application of AMCS to the few carefully selected patients with refractory PCCS in order to optimise the cost-benefit equation. Our results reflect findings from previous studies. Our study showed survivors enjoyed a reasonable quality of life.