Refractory post-cardiotomy cardiogenic shock (PCCS) is a relatively rare phenomenon that can lead to rapid multi-organ dysfunction syndrome and is almost invariably fatal without advanced mechanical circulatory support (AMCS), namely extra-corporeal membrane oxygenation (ECMO) or ventricular assist devices (VAD). In this multicentre observational study we retrospectively analyzed the outcomes of salvage venoarterial ECMO (VA ECMO) and VAD for refractory PCCS in the 3 adult cardiothoracic surgery centres in Scotland over a 20-year period.
Methods
The data was obtained through the Edinburgh, Glasgow and Aberdeen cardiac surgery databases. Our inclusion criteria included any adult patient from April 1995 to April 2015 who had received salvage VA ECMO or VAD for PCCS refractory to intra-aortic balloon pump (IABP) and maximal inotropic support following adult cardiac surgery.
Results
A total of 27 patients met the inclusion criteria. Age range was 34–83 years (median 51 years). There was a large male predominance (n = 23, 85 %). Overall 23 patients (85 %) received VA ECMO of which 14 (61 %) had central ECMO and 9 (39 %) had peripheral ECMO. Four patients (15 %) were treated with short-term VAD (BiVAD = 1, RVAD = 1 and LVAD = 2). The most common procedure-related complication was major haemorrhage (n = 10). Renal failure requiring renal replacement therapy (n = 7), fatal stroke (n = 5), septic shock (n = 2), and a pseudo-aneurysm at the femoral artery cannulation site (n = 1) were also observed. Overall survival to hospital discharge was 40.7 %. All survivors were NYHA class I-II at 12 months’ follow-up.
Conclusion
AMCS for refractory PCCS carries a survival benefit and achieves acceptable functional recovery despite a significant complication rate.
Abkürzungen
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
ICD
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
Background
Cardiogenic shock following cardiac surgery can affect as many as 2–6 % of patients undergoing routine surgical coronary revascularization or valve surgery [1‐4]. Although the majority of these patients respond to inotropic support and/or intra-aortic balloon pump counter pulsation (IABP) support, 0.5–1.5 % of patients demonstrate a rapid and progressive decline in their haemodynamic parameters in the immediate aftermath of cardiopulmonary bypass [5]. The occurrence of post-cardiotomy cardiogenic shock (PCCS) can be unpredictable and can occur in patients with normal preoperative myocardial function as well as those with pre-existing impaired function [6]. Refractory PCCS leads to vital organ hypoperfusion and is almost universally fatal [4, 7‐9] without the use of advanced mechanical circulatory support (AMCS) devices such as extracorporeal membrane oxygenation (ECMO) or ventricular assist devices (VAD).
In our previous study we looked at the outcomes of AMCS utilization at the Edinburgh heart center’s cardiothoracic surgery department (a non-transplant, intermediate-sized, adult cardiothoracic surgery centre) in Scotland [10]. This current multicentre observational study aims to consolidate our previous findings and looks at the 20-year outcomes of AMCS utilization to salvage refractory PCCS patients in all the 3 cardiothoracic surgery centres in Scotland.
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Methods
Scottish adult cardiothoracic surgical services are provided by three regional centres covering a population of 5.2 million individuals [11]. The relevant data was collected from the databases of the Royal Infirmary of Edinburgh (surgical case load ≈ 900/year), the Golden Jubilee National Hospital in Glasgow (surgical case load ≈ 1300/year), and the Aberdeen Royal Infirmary (surgical case load ≈ 500/year). Our inclusion criteria included any adult patient from April 1995 to April 2015 who had received salvage VA ECMO or VAD for PCCS refractory to IABP and inotropic support following adult cardiac surgery. We acquired information regarding the patients’ 12 month follow-up status by accessing the cardiology follow-up clinic letters on the TrakCareR system in Edinburgh, the AMCS database in Glasgow, and through making direct enquiries with the surgeons involved in the long-term outcomes of the patients in Aberdeen via email and telephone communications.
The AMCS devices utilised at the Royal Infirmary of Edinburgh over the defined study period were LevitronixR CentriMag II for ECMO and Medtronic Bio-MedicusR 560 for short-term VAD support. Over the same time period, the AMCS devices used at the Golden Jubilee National Hospital in Glasgow and the Aberdeen Royal Infirmary cardiac surgical units was the CentriMag device for both VA ECMO and short-term VAD support.
Results
A total of 28 patients met the inclusion criteria with one patient excluded due to lack of recorded information in the TrakCareR database regarding the type of AMCS support used, any potential complications and the short and the long-term outcomes of this individual. Overall, 16 patients from the Royal Infirmary of Edinburgh met the inclusion criteria, 8 patients from the Golden Jubilee National Hospital in Glasgow and 3 patients from Aberdeen Royal Infirmary cardiothoracic surgery unit. The reason why more cases belonged to Edinburgh rather than Glasgow, despite the latter being a larger unit, was because AMCS was rarely used to salvage refractory PCCS patients in the west of Scotland prior to 2007 (the year of the merger between Glasgow Royal Infirmary and the Glasgow Western Infirmary forming the Golden Jubilee National Hospital).
Of the total 27 patients from the 3 centres, the age range was 34–83 years (median 59 years). There was a large male predominance of 23 (85 %). Four patients (15 %) had undergone re-operative cardiac surgery. One patient (3.7 %) had undergone AMCS following the repair of a traumatic ascending aortic transection after a road traffic accident. Overall, 23 patients (85 %) had received a single run of VA ECMO of which 14 (61 %) had received central ECMO and 9 (39 %) had received peripheral ECMO. Four patients (15 %) had short-term VADs (1 BiVAD, 1 RVAD and 2 LVAD). The mean duration of AMCS was approximately 5.43 days (Range < 1 day–33 days). The most common procedure-related complication was major haemorrhage (37 %). Renal failure requiring renal replacement therapy (26 %), stroke (19 %) and peripheral limb ischaemia (15 %, Fig. 1) were also recorded. Logistic EuroSCORE ranged from 2.08 to 73.26. More detailed patient baseline characteristics are tabulated in Table 1.
Fig. 1
Bar chart illustrating the number and nature of complications within cohort
Table 1
Patient baseline characteristics
Age & Gender
Date of surgery
Original operation
Duration and Mode of AMCS
AMCS Complication/s
Outcome
Patient 1
76 year old male
2012
Re-do sternotomy and AVR
Salvage peripheral VA ECMO due to postoperative pulmonary haemorrhage and cardiogenic shock
Femoral artery cannulation site pseudoaneurysm
Alive
NYHA I (No breathlessness of exertion, back to work)
Major haemorrhage from cannulation site
Patient 2
40 year old male
2014
Re-do, Re-do sternotomy for type A aortic dissection: Bentall procedure
Salvage RVAD due to VF arrest and severe LVSD after weaning from CPB
Major haemorrhage and re-exploration in the operating theatre
Alive
NYHA II (Breathless on exertion)
Patient 3
82 year old male
2006
MV Repair and CABG
3 Days
Could not be weaned from ECMO with severe biVent failure and
Died in CTICU
VA ECMO as unable to wean from CPB
COD: BiVent failure
Patient 4
72 year old Female
2011
AVR
9 Days
Septic shock
Died in CTICU
VA ECMO as unable to come off CPB
Limb ischaemia
COD: Septic shock
Patient 5
71 year old male
2011
CABG and AVR
2 Days
ECMO cannulation site bleeding and haematoma explored
Died in CTICU
Peripheral VA ECMO as unable to come off CPB
COD: Shock (unknown cause)
Renal failure a
Patient 6
83 year old female
2012
MVR and CABG
<1 Day
None
Died in CTICU
Peripheral VA ECMO as unable to wean from CPB
COD: BiVent failure
Patient 7
70 year old male
2013
Re-do sternotomy and AVR
33 Days
Major CVA
Died in HDU
VA ECMO for cardiac failure. Successfully weaned from ECMO
COD: severe Respiratory failure
Patient 8
72 year old male
2013
Re-do sternotomy and AVR
<1 Day
ECMO cannulation femoral artery dissection
Died in CTICU
VA ECMO after iatrogenic aortic dissection leading to cardiogenic shock during Femoral cannulation for CPB
COD: Major CVA
Major haemorrhage
Major CVA
Patient 9
51 year old male
2013
Re-suspension of Aortic valve and repair of type A aortic dissection
1 Day
Major cannulation site haemorrhage
Died in CTICU
Peripheral VA ECMO for cardiogenic shock
COD: Haemorrahgic shock and BiVent failure
Patient 10
34 year old female
2014
IVC Leiomyosarcoma resection
3 Days
None
Died in CTICU
VA ECMO for postoperative cardiogenic shock for intraoperative MI
COD: BiVent failure from acute MI
Patient 11
65 year old male
2013
CABG
2 Days
Renal failurea
Died in CTICU
Salvage VA ECMO for cardiogenic shock
Hepatic failure
COD: MODS
Pulmonary oedema
Patient 12
71 year old male
2015
CABG
3 Days
Major haemorrhag e: Re-opening for bleeding x4
Died in CTICU
VA ECMO as unable to wean from CPB
COD: biventricular failure and septic shock
limb ischaemia
Patient 13
49 year old male
1997
CABG
VA ECMO as unable to wean from CPB
Note recorded
Alive
(Died 2004)
NYHA II
Patient 14
69 year old male
2004
MVR and CABG for mitral valve IE
VA ECMO as unable to wean from CPB
CVA and seizures
Alive
Renal failure a
NYHA II
Patient 15
41 year old female
2005
Aortic transection and diaphragm rupture
VA ECMO
Not recorded
Alive
NYHA I
Patient 16
59 year old male
2006
Type A aortic dissection
2 Days
Not recorded
Died
Peripheral VA ECMO as unable to wean from CPB
COD: Bivent failure
Patient 17
21 year old male
2014
AVR
3 days
ECMO cannulation site bleeding-required re-exploration
Alive
Peripheral VA ECMO
NYHA I
Cardiac tamponade
Patient 18
51 year old male
2014
AVR
6 days
CVA and Seizures
Died in ICU
Peripheral VA ECMO
limb ischaemia
COD: status epilepticus
Patient 19
46 year old male
2014
CABG
2 days
Major haemorrahage
Died in ICU
Peripheral VA ECMO converted to central VA ECMO due to peripheral ischaemia
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
aAll patients with renal failure required renal replacement therapy
×
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The most common cause of death (COD) was refractory biventricular failure that failed to recover sufficiently to allow weaning from AMCS (22.2 %, Fig. 2). In these patients care was withdrawn. One patient died due to a combination of biventricular failure and haemorrhagic shock and another patient died from a combination of biventricular failure and septic shock whilst on VA ECMO. The survival rate to hospital discharge was 40.7 % (Fig. 3). The follow-up data showed that the survivors were all NYHA class I-II functional status at 12 months.
Fig. 2
Bar chart illustrating the number and causes of death within cohort. AV: atrioventricular
Fig. 3
Kaplan-Meier curve of survival, x-axis represents follow-up (FU) in days and y-axis represents cumulative survival (Cum survival)
×
×
Statistical analysis
Statistical analysis was performed using the Fisher’s exact and Pearson’s chi2 tests. Univariate analysis was performed. Table 2 demonstrates the baseline statistics data and the analytical methods used in this study.
Table 2
Demonstrates variables used for statistical analysis. Fisher’s exact test and Pearson’s chi test (Log. EuroSCORE) were utilized for statistical analysis
Factors attributed to mortality and statistical analysis
Characteristics analyzed
Alive
Dead
Odds ratio (95 % Conf. interval)
p-value
Age (years)
0–65
8
10
2.8 (0.362853–33.74714)
0.24
> 65
2
7
Gender
Male
9
14
1.928571 (0.1270413–112.3145)
0.5
Female
1
3
Type of center
Transplant
4
5
0.625 (0.0921389–4.488993)
0.44
Non-transplant
6
12
Prev. cardiac surgery
Re-do surgery
2
2
0.5333333 (0.0335265–8.873345)
0.48
First time surgery
8
15
Surgical complexity
Isolated surgery
6
10
1.05 (0.1662785–7.107629)
0.64
Complex surgery
4
7
Type of Support
VAD
3
1
0.1458333 (0.0026189–2.352801
0.13
ECMO
7
16
Duration of Support
0–7 days
8
15
0.5333333 (0.0335265 8.873345)
0.47
> 7 days
2
2
Support complications
Major haemorrhage
5
5
0.4166667 (0.0620347–2.804408)
0.25
No major haemorrhage
5
12
Major CVA
1
4
2.769231 (0.2140667–151.2664)
0.37
No major CVA
9
13
Renal failure
3
4
0.7179487 (0.0910803–6.420841)
0.52
No renal failure
7
13
Log. EuroSCORE
0–10
1
3
0.36 (Pearson’s chi2 test)
10–20
1
6
> 20
4
3
Score not available
4
5
Table information: Prev.cardiac surgery denotes whether the patient had had previous cardiac surgery through median sternotomy (i.e. redo surgery). Isolated surgery refers to whether the operation was isolated coronary artery bypass grafting surgery (CABG) or single valve surgery. Complex cardiac surgery refers to combined valve, CABG and/or aortic surgery. Type of center denotes whether the operating hospital in which the operation was performed was a cardiopulmonary transplant center. Log. EuroSCORE refers to logistic EuroSCORE
Discussion
Our study demonstrates that AMCS used for the treatment of refractory PCCS can lead to good outcomes for a significant number of patients, with 40.7 % surviving to hospital discharge and all surviving patients were graded as either NYHA class I or II at 12 months’ post-discharge. Without AMCS, it is likely that the vast majority of these patients would have died. Ours is also the first multi-centre study of its kind to emerge from the UK and one of the few studies to examine functional outcomes post AMCS utilisation for refractory PCCS.
Recent evidence has demonstrated that modern, continuous-flow AMCS devices, such as the CentriMagR that was used in our centres, can lead to improved survival in patients with PCCS [12‐14]. In the largest cohort, Hernandez et al. [3] collated data from 5735 patients who underwent salvage VAD for refractory PCCS. They reported a 54.1 % survival rate to hospital discharge and concluded that VAD is a valuable, life-saving therapeutic manoeuvre. By comparison, the survival rate in our study was lower but firm conclusions are difficult given the low number of patients in our cohort. However, other smaller studies (relative to the Hernandez study) [5, 15‐18] all using either ECMO or VAD for refractory PCCS, reported less impressive survival to hospital discharge rates of 24.8 %–37 % and a 5 year survival of 13.7 %–16.9 %. Unfortunately, we do not have long-term survival data as many of the survivors were ultimately discharged from the outpatient clinics when no further medical or surgical interventions were required, hence longer term follow up data post out-patient clinic discharge had not been recorded in the database.
We identified advanced age to be a factor leading to an adverse outcome, although again, owing to our smaller numbers, this did not reach statistical significance. Most (64 %) of the survivors were under 60 years of age. Furthermore, the emergent nature of surgery and pre-existing, preoperative severe left ventricular impairment were also identified as probable factors leading to an adverse outcome.
Evidence suggests that early device implantation [6] and appropriate patient selection through a multidisciplinary team approach is paramount to an optimal outcome [10]. There are no national or local protocols for identifying suitable patients for AMCS with refractory PCCS in Scotland: instead, decisions are based on a case-by-case assessment involving a multidisciplinary team (cardiac surgeon, department head, anaesthetist, and perfusionist) in each of the three hospital sites. We continue to believe that this is the best approach to patient selection rather than a standardised algorithmic approach because it ensures an ethically appropriate decision for the patient whilst optimising the cost-benefit equation. The decision regarding when to initiate AMCS support was made for most patients whilst in theatre in those whom weaning from CPB was not possible, although a few were commenced AMCS whilst in ICU. The time to AMCS and how this correlates to survival is an important variable that regrettably was not consistently recorded in our patient cohort.
AMCS devices are expensive [9, 19, 20] and this, coupled with a potentially prolonged length of stay in ICU, means that cost is an important factor in the decision-making process, particularly within the UK NHS. Indeed, decision-makers have opted to centralise AMCS funding to a restricted number of the larger cardiothoracic centres [21], invariably depriving other units of this potentially life-saving resource. Understandably, this has led to expressions of consternation [21]. In our cohort, the longest duration on AMCS was 33 days (patient 7). This patient was successfully weaned from VA ECMO but died whilst in critical care from a stroke, which may have been a complication from AMCS employment.
The NYHA functional outcomes for our patients were also very positive. Unfortunately, many previous AMCS studies for refractory PCCS do not report such findings, although we did identify two studies, each with similar outcomes to ours. Ko et al. [17] detailed a cohort of 76 patients undergoing ECMO support for refractory PCCS. They reported that all survivors were of NYHA classes I or II at 32 +/− 22 month follow-up. Pennington et al. [15] reported on refractory PCCS support with VAD and found that all survivors were “leading active lives”. In 72.7 % of their survivors, ejection fraction had normalized on follow-up echocardiography.
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Clearly, given that we only identified 27 patients undergoing AMCS over a 20-year period, and despite our pooled hospital case volume, we acknowledge that the Scottish approach to institution of AMCS for refractory PCCS has been relatively conservative. This can partly be explained by the fact that salvage AMCS was not employed in the west of Scotland until 2007. Also, our general approach to institution of AMCS dictates that such modalities are instituted only if there is a reversible cause of the cardiogenic shock, which is reflected by our reasonable survival rate. Other possible reasons for underutilization may include: scarcity of resources, prohibitive costs, and lack of consistent evidence for the benefit of AMCS.
The decision to institute AMCS must also be balanced with due consideration of the associated risks of this invasive modality, many of which are potentially life-threatening. Common device-related complications include: haemorrhage, thrombus formation and embolization, stroke, device-related infection, limb ischaemia, and multi-organ dysfunction syndrome/failure [1, 2, 15, 17, 22, 23]. In our cohort, the most common procedure-related complication was major haemorrhage. Renal failure requiring renal replacement therapy, stroke, and peripheral limb ischaemia also occurred with comparable rates to previous studies.
Given the scarcity of donor hearts in the UK, research continues to focus on implantable AMCS devices as a bridge to recovery, bridge to transplant, or as destination therapy [19]. However, none of our patients were transplanted during the study period and none had implantable long-term VADs.
Finally, this study is limited by the small number of subjects (as previously discussed) and its retrospective nature. It nevertheless reaffirms the findings of our previous study, which reported a good survival rate and acceptable quality of life for patients who received AMCS for refractory PCCS and survived to hospital discharge.
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Conclusions
AMCS devices can be used to salvage a significant proportion of patients with refractory PCCS who would otherwise not survive. These patients are also likely to enjoy a reasonable quality of life. However, ACMS devices are associated with high rates of severe, systemic and device-related complications as well as being costly. Multidisciplinary teams experienced with patient selection and decision-making are imperative to help ensure appropriate use of AMCS and the best patient outcomes.
Acknowledgements
None.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Availability of data and materials
The data gathered for this study can be retrieved from the Royal Infirmary of Edinburgh, Golden Jubilee National Hospital and Aberdeen Royal Infirmary cardiothoracic surgery databases and TrakCareR databases. The raw data can be requested from the corresponding author (M. Khorsandi).
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Authors’ contributions
MK principal investigator, manuscript preparation and drafting, data collection, SD: manuscript drafting, AS manuscript drafting and assistance with data collection, KB: manuscript drafting, FM: assistance with data collection, OB: statistical analysis, PC: manuscript drafting, VZ: manuscript drafting, GB: manuscript drafting, NAA: project supervisor and manuscript drafting. All authors read and approved the final manuscript.
Competing interest
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
Not applicable.
Meeting presentation
Oral presentation at the SCTS conference Birmingham, UK, 13-15/March/2016.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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