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European Journal of Heart Failure 2007 9(8):845-849; doi:10.1016/j.ejheart.2007.05.002
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© 2007 European Society of Cardiology

Similar transplantation outcomes in patients bridged with cardiac assist devices for acute cardiogenic shock versus chronic heart failure

Stavros G. Drakosa,b, Abdallah G. Kfourya,*, James W. Longa, James C. Stringhamb,c, Edward M. Gilbertb,c, Benjamin D. Hornea, Mary-Beth E. Haganc, Karah Nelsona and Dale G. Renlunda,b

a Utah Transplantation Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, LDS Hospital Salt Lake City, Utah, United States
b University of Utah School of Medicine Salt Lake City, Utah, United States
c George E. Wahlen Veterans Affairs Medical Center Salt Lake City, Utah, United States

* Corresponding author. Division of Cardiology, LDS Hospital, 8th Avenue and C Street, Salt Lake City, Utah 84143, United States. Tel.: +1 801 408 5319 E-mail address: akfoury{at}intermountainmail.org.


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: Heart failure (HF) patients may require cardiac assist device implantation prior to transplantation (Tx) because of either acute cardiogenic shock (ACS), with no prior history of HF, or for progression of pump failure in the setting of chronic HF.

Aims: To investigate whether patients implanted with a cardiac assist device for ACS, have similar post-Tx outcomes as those who underwent cardiac assist device implantation because of progressive chronic HF.

Methods and results: We compared post-Tx outcomes of consecutive patients bridged due to ACS (Acute Group) with the outcomes of patients bridged due to deterioration of chronic HF (Chronic Group). Seventy-three patients had a cardiac assist device implanted and underwent subsequent cardiac Tx. Thirty-five patients (48%) had a cardiac assist device implanted due to ACS, most often caused by massive acute myocardial infarction, and 38 patients (52%) because of progressive chronic HF. Despite greater compromise at the time of implantation, the Acute Group recovered satisfactorily and underwent Tx with similar post-Tx survival rates as the Chronic Group patients [1-year survival: 88.6% vs 86.8%, p=0.80, actuarial survival (mean follow-up 4.2 years): 80.0% vs 81.6%, p=0.86)]. Furthermore, no significant differences were observed between the 2 groups in various post-Tx events.

Conclusion: Patients with ACS who underwent emergency cardiac assist device implantation as bridge to Tx had similar post-Tx outcomes as their more chronically ill counterparts who underwent device implantation on a non-urgent basis.

Key Words: Chronic heart failure • Acute cardiogenic shock • Cardiac assist devices • Heart transplantation

Received December 5, 2006; Revised March 12, 2007; Accepted May 1, 2007


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
The advent of mechanical assistance for the failing myocardium has been life saving for chronic heart failure patients awaiting heart transplantation [1-3]. However, many patients without prior history of chronic heart failure undergo implantation of a cardiac assist device on an emergency basis due to refractory acute cardiogenic shock (ACS) as a bridge to either recovery or transplantation [4-9]. In the case of elective implementation of long-term mechanical circulatory support (MCS) as bridge to transplant the chronic heart failure patients undergo a comprehensive evaluation to assess the need for transplant as well as to identify significant comorbidities that could shorten post-transplant survival [10-12]. In contrast, ACS patients' critical condition does not permit thorough transplant evaluations before ventricular assist device insertion [13]. Whether undetected problems due to the brevity of these emergency evaluations negatively impacts outcomes after cardiac transplantation compared with those candidates with non-urgent evaluations is unknown.

We have previously reported similar post-transplant outcomes of patients bridged to transplantation with MCS compared to their non-MCS counterparts [14]. In this report, with almost the same MCS patient population as in our previous report, we sought to investigate whether patients with no prior history of heart failure who require emergency cardiac assist device implantation as a bridge to transplant because of ACS, have similar post-transplant outcomes as those who underwent non-urgent device implantation because of progressive chronic heart failure.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
We retrospectively compared post-transplantation outcomes of two groups of patients who were bridged to heart transplantation with chronic MCS. In the first group, MCS was used to treat patients suffering from ACS refractory to optimal conventional treatment (Acute Group). ACS was diagnosed when the following criteria were fulfilled: systemic hypotension (a systolic blood pressure of <90 mm Hg), end-organ hypoperfusion (cool extremities or a urine output of <30 ml/h), a cardiac index of no more than 2.2 L/min/m2 of body-surface area and a pulmonary-capillary wedge pressure of at least 15 mm Hg. In the second group we included end-stage chronic heart failure patients who had MCS deployed due to clinical and haemodynamic deterioration while waiting for heart transplantation (Chronic Group). The HeartMate IP or VE Left Ventricular Assist System (Thoratec, Pleasanton, CA) and the CardioWest Total Artificial Heart (SynCardia Systems Inc, Tucson, AR) were the devices utilized.

Various short-term (<1 month) and long-term (2-12 months) post-transplantation outcomes were compared between the 2 groups. Infection was defined as fever >38.1C, elevated white blood cells and positive cultures of blood or other fluid, requiring intravenous antimicrobial treatment. Rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade ≥3A and haemodynamically significant rejection was defined as rejection requiring inotropic support. Acute renal dysfunction was defined as peak serum creatinine >3 mg/dl and acute hepatic dysfunction was defined as liver function tests elevated more than 3 times normal. Chronic renal insufficiency was defined as a serum creatinine measuring consistently >2 mg/dl which persisted for 6 months or more. Allograft dysfunction was defined as acute cardiac allograft dysfunction requiring intraaortic balloon counterpulsation or other temporary mechanical support. Thoracic complications included pericardial tamponade (requiring pericardiocentesis), adult respiratory distress syndrome, pneumothorax, haemothorax, and pleural effusion requiring thoracentesis. Thromboembolic complications included pulmonary embolism and deep vein thrombosis. Central nervous system complications included stroke and anoxic brain damage. Atrial dysrhythmias included atrial fibrillation, atrial flutter, and permanent pacemaker implantation. Gastrointestinal complications included ileus, pancreatitis, oesophageal perforation and dysphagia. Neurologic complications included peripheral neuropathy, leg cramps and restless leg syndrome. Allograft coronary artery disease was defined as stenosis >50% of at least one coronary artery. The investigation conforms with the principles outlined in the Declaration of Helsinki and our institutional committee on human research has approved the study protocol.

2.1. Statistical methods
Comparisons of demographic or clinical factors between the two groups of patients were analysed with the X2 and Student's t-test. Kaplan-Meier survival estimates were compared with the long-rank test. Cox regression was used to compute the survival function for acute vs. chronic with adjustment for significant and confounding covariables. Survival and event-free (re-transplantation, ISHLT 3A or worse rejection, or haemodynamically significant rejection) survival were evaluated. Due to the relatively small number of individuals in the study, all regression models were built with forced entry of only 4-6 variables simultaneously, with the final models including only 3 variables. Various demographic, pre-implantation, and post-implantation variables were considered as potential predictors in regression modelling (age, gender, type of device, history of diabetes mellitus or peripheral vascular disease, pulmonary function tests, ischaemic time, donor age, donor positive CMV, recipient positive CMV, proportion of male donors, body surface area, duration of mechanical support, New York Heart Association functional class at implant, heart rate at implant, filling pressures and cardiac output at implant, left ventricular ejection fraction at implant, laboratory values at implant as creatinine, blood urea nitrogen, sodium, bilirubin, haemoglobin, inotrope dependency at implant, need for IABP utilization at implant, panel reactive antibody at transplant). A p-value less than 0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
We retrospectively reviewed 279 patients who underwent cardiac transplantation from 1993 to 2002. In this study we are reporting only the outcomes of patients who required pre transplant MCS and were finally successfully bridged to heart transplantation (n=73). In thirty-five (48%) of these patients MCS was implemented due to ACS (Acute Group) and in the remaining 38 (52%) patients due to deterioration of chronic heart failure (Chronic Group).

Heart failure aetiology is described in Table 1 and baseline patient characteristics are described in Table 2. The Acute Group was haemodynamically much more compromised at the time of implantation than the Chronic Group, as manifest by the higher need for various intravenous inotropic and vasoactive agents and more frequent use of intraaortic balloon counterpulsation (Table 2). Notably, at implantation time one quarter of the Acute Group patients developed peri-operatively severe acute renal failure requiring temporary dialysis as opposed to only two patients in the Chronic group.


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  		Table 1 Heart failure aetiology

 


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  		Table 2 Patient characteristics

 
As shown in Table 3, no differences were observed between the two groups in various post-transplant outcomes such as duration of intensive care unit stay, extubation time and the post-operative renal and hepatic function. The Acute Group tended to receive more transfusions after transplantation.


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  		Table 3 Post-transplantation outcomes

 
Short term post-transplantation complications (<1 month) such as acute renal and hepatic dysfunction, graft dysfunction, reoperation rates, infections, atrial dysrhythmias, thoracic, thromboembolic, central nervous system and gastrointestinal complications were found to be similar between the two groups. However, regarding long-term post-transplant complications (2-12 months) the Chronic group tended to have an increased incidence of infections (23.7% vs 5.7%, p=0.07) whereas other complication such as chronic renal insufficiency, allograft coronary artery disease, atrial dysrhythmias, thromboembolic, thoracic, gastrointestinal and neurologic complications were comparable between the two groups.

Furthermore, no differences were seen in 1-year post-transplantation survival (Fig. 1) and actuarial post-transplantation survival (mean follow-up 4.2 years, Fig. 2). A combined endpoint using death, re-transplantation, ISHLT 3A or worse rejection, or haemodynamically significant rejection was evaluated. As seen in Fig. 3, the Acute group did not differ from the Chronic group.


Figure 01
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  		Fig. 1 Post-transplantation 1-year survival. MCS: Mechanical circulatory support.

 


Figure 02
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  		Fig. 2 Post-transplantation actuarial survival. MCS: Mechanical circulatory support.

 


Figure 03
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  		Fig. 3 Freedom from combined end-point (death or re-transplantation or rejection or haemodynamically significant rejection). MCS: Mechanical circulatory support.

 
In multivariable analyses, survival tended to be predicted by gender (improved survival for males) and higher left ventricular ejection fraction at implant, but not by MCS aetiology, i.e. Acute vs. Chronic (hazard ratio=1.08, p=0.89 for Acute). Furthermore, multivariable analyses revealed that event-free survival was not found to be predicted by MCS aetiology (hazard ratio=1.04, p=0.89).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
Bridging to transplantation with long-term MCS has been life saving for many patients with end-stage chronic heart failure [1-3]. As shown both by our group and others [14-17], the implementation of chronic MCS as bridge to transplant in end-stage heart failure patients was associated with post-transplant outcomes similar or even better compared to the outcomes of patients that were transplanted without requiring such a bridge. Furthermore, quite often acutely ill patients suffering from ACS refractory to optimal conventional treatment require implementation of MCS [4-9,18-26]. In these patients suffering from various causes of ACS, such as acute myocardial infarction, post-cardiotomy failure, acute myocarditis etc, the probability of myocardial recovery to the point the cardiac assist device can safely be withdrawn is highly unpredictable [4-7]. Sometimes a short-term assist device serves as bridge to other therapeutic management and it is not uncommon to have these critically ill patients undergoing high risk re-operations for substitution of a short-term with a long-term cardiac assist device (bridge to bridge) [27].

Taking all these in account, an emerging therapeutic strategy, that has to be validated, is the direct implementation of long-term cardiac assist devices, approved to be used as bridge to transplantation, for patients suffering from refractory ACS [9,13,27-29]. One of the problems with this therapeutic strategy is that it is almost impossible to have these marginal patients undergo thorough pre-transplant evaluations to assess their transplant candidacy eligibility [13,28]. Even in the case that this could be done it is not always easy to predict in advance whether a profound cardiogenic shock patient whose vital organs are being fully supported both medically and mechanically would finally recover to the point he can safely undergo a heart transplantation [28].

In our study, we found that the ACS patients that survived to transplantation after implantation of a long-term cardiac assist device had similar post-transplant outcomes as their more chronically ill counterparts. As a limitation of this study could be considered the fact we do not provide any data on the post-implantation outcomes of all ACS patients that required cardiac assist device implantation in our program but only data for the proportion of these patients that finally survived to transplantation. On the other hand though, the issue we really intended to address in this study was not the effectiveness of cardiac assist devices in treating refractory ACS. Regardless of the short-term outcome of such a therapeutic approach, what we really wanted to focus on is whether the proportion of ACS patients that survives after requiring to be mechanically assisted can subsequently be safely transplanted with acceptable post-transplant outcomes. Our data show that once resuscitated from such acute catastrophic situations these critically ill patients can subsequently be transplanted with morbidity and mortality rates similar to those of their more chronically ill counterparts that also required to be mechanically bridged.

Nevertheless, the above mentioned issue of the effectiveness of MCS in the setting of refractory ACS and the post-operative outcomes of this therapeutic approach, an issue that we have not addressed in our study, is of great importance and needs to be investigated further [13,30]. In a recent report from the Columbia-Presbyterian group [13], of the 115 patients who required left ventricular assist device support, 73 (63%) patients required emergency placement due to acute cardiogenic shock; 70% of these patients survived to transplant compared with 83% of those with non-urgent device implantation (not statistically significant). Furthermore, in accordance to our study, in that report the post-transplant survival outcome was similar for patients with emergency device placement and those with non-urgent placement [13].

A potential limitation of this single-program study could be the modest sample size of the patient cohort, so a survival difference might have been missed owing to insufficient power. Because of this we included in our analysis a lot of short and long-term post transplant morbidity variables, such as if one of these variables was found to be significantly different it could then suggest the probability of adverse outcomes in terms of survival in a larger patient cohort or a longer follow-up. Nevertheless, no significant difference was identified between the two groups in any of the studied variables.

In conclusion, in our study patients with acute cardiogenic shock bridged to transplantation with cardiac assist device had similar post-transplant outcomes as their more chronically ill counterparts. Therefore, the timely application of long-term mechanical circulatory support for acute catastrophic situations appears warranted despite the abbreviated transplant evaluations and should be investigated further.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

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This Article
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Right arrow FREE Full Text (PDF) Freely available
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