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J Thorac Cardiovasc Surg 2004;127:1309-1316
© 2004 The American Association for Thoracic Surgery
Cardiopulmonary support and physiology |
a Department of Surgery, Division of Cardiothoracic Surgery, Columbia University, College of Physicians and Surgeons, New York, NY, USA
b Department of Surgery, Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
Received for publication March 20, 2003; revisions received July 20, 2003; accepted for publication July 31, 2003.
* Address for reprints: Yoshifumi Naka, MD, PhD, Columbia University, College of Physicians and Surgeons, 177 Fort Washington Ave, Milstein Hospital 7GN-435, New York, NY 10032, USA
yn33{at}columbia.edu
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Abstract |
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 Top Abstract Patients and methodsResultsDiscussionReferences |
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METHODS: From August 1990 through January 2003, 243 patients underwent implantation of Thoratec HeartMate devices as a bridge to transplantation. This included 52 (21.4%) pneumatic devices, 17 (7.0%) dual-lead vented electric devices, and 174 (71.6%) single-lead vented electric devices.
RESULTS: Mean age was 49.7 ± 13.7 years. Mean support time was 78.1 ± 82.9 days (0-541). Bridging success increased from 63.5% (n = 33) for pneumatic devices to 64.7% (n = 11) for dual-lead vented electric devices and 72.4% (n = 126) for single-lead vented electric devices (P = .005). Posttransplant 1-, 3-, and 5-year actuarial survival increased from 87.5%, 78.1%, and 71.9% in patients with pneumatic devices to 91.5%, 86.9%, and 81.3%, respectively, for patients with single-lead vented electric devices. Device infection and malfunction occurred in 17.7% (n = 43) and 12.8% (n = 31) of patients, respectively.
CONCLUSIONS: Successful bridging to transplantation and posttransplant survival has improved over time. Left ventricular assist devices have become increasingly more effective in bridging patients with end-stage heart failure to transplantation. This is likely due to a combination of better patient selection, improvements in clinical practice, and evolution in device design.
Over the last 12 years, the HeartMate (Themocardiosystems, Woburn, Mass) has been the preferred device at our institution for bridging patients with end-stage heart failure to transplantation and has been used with the greatest frequency.9-12 With this device, patients can be stabilized and discharged from the hospital to wait for their heart transplant at home.13-15
Early survival data of patients undergoing LVAD insertion revealed greater than 30% hospital mortality. Since the initiation of our LVAD program in 1990, there have been many clinical improvements in perioperative care.9 We reviewed our 12-year experience with 3 different HeartMate devices, focusing on the temporal changes in duration of support, bridge to transplant success, and posttransplant survival. Additionally, we evaluated the incidence of the most common device-related complications, including infection, device malfunction, and stroke, as well as causes of death for those patients who expired on LVAD support. Finally, we outlined preoperative, intraoperative, and postoperative improvements in care as well as advancements in device design that have favorably impacted the success of LVADs in bridging patients to transplantation.
We challenged ourselves to answer the following questions: Has bridging success to transplantation improved over the years as device design and clinical practices have evolved? What were the primary advancements in preoperative, intraoperative, and postoperative care that may have been responsible for improved bridging to transplant success? Finally, was our recently reported LVAD screening scale accurate in its ability to predict survival to transplant?
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Patients and methods |
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TopAbstractPatients and methodsResultsDiscussionReferences |
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Duration of support, bridging to transplant success, survival posttransplant, incidence of infection, and device malfunction were evaluated based on type of device and time period. Infection was defined as the presence of a positive culture along with a leukocytosis. Device malfunction was categorized into electrical, mechanical, and technical causes.
We previously reported a preoperative scoring system that predicts successful bridging to transplant.16 LVAD implantation scores, derived from 5 clinical variables, including ventilatory dependence, postcardiotomy shock, previous LVAD, central venous pressure >16 mm Hg, and prothrombin time >16 seconds, were calculated for patients with SLVE devices.16 LVAD scores were classified as low (0-4), medium (5-7), and high (8-10), with an inverse relationship between score and clinical stability. Mean LVAD score during each year was calculated and all years were compared.
Statistical analysis
Data were represented as frequency distributions and simple percentages. Values of continuous variables were expressed as a mean ± standard deviation (SD). Continuous variables were compared using analysis of variance (ANOVA-Bonferroni), whereas categorical variables were compared by means of chi-square tests. Kaplan-Meier analysis was used to calculate long-term survival along with a log-rank P value when comparing groups. Actuarial survival was calculated by constructing life tables. Significant predictors of bridging to transplant success were investigated by examining the association between various preoperative variables and bridging success in univariate analysis, followed by a stepwise logistic regression analysis on factors demonstrated to be significant in univariate analysis. Variables included age, sex, race, etiology of heart failure, development of infection, device malfunction, and LVAD implantation scores. All data were analyzed utilizing SPSS 11.5 (SPSS Inc, Chicago, Ill).
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Results |
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TopAbstractPatients and methodsResultsDiscussionReferences |
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Bridging to transplant success
Bridging to transplant success significantly increased from 63.5% (n = 33) for PNEUM devices to 72.4% (n = 126) for SLVE devices (P = .005; Figure 1). Causes of death for patients who expired on LVAD support are listed in Table 2.
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Infection and device malfunction
The overall incidence of infection was 17.7% (n = 43), occurring in 25.0% (n = 13) of patients with PNEUM devices, 0.0% (n = 0) of patients with DLVE devices, and 17.2% (n = 30) of patients with SLVE devices (Table 1). Device malfunctions occurred in 15.4% (n = 8) of PNEUM devices, 29.4% (n = 5) of DLVE devices, and 10.3% (n = 18) of SLVE devices (Table 3). When considering only those device malfunctions that were clinically significant (excluding incidental findings at explantation), the incidence was 11.5% (n = 6) in PNEUM devices, 23.5% (n = 4) in DLVE devices, and 5.7% (n = 10) in SLVE devices (Table 3).
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LVAD score
LVAD implantation scores increased from 2.6 ± 3.1 in 1996, to 3.8 ± 3.3 in 1997, to 4.9 ± 3.6 in 1998, to 5.3 ± 3.5 in 1999, and to 5.4 ± 3.8 in 2000. Scores then decreased to 5.3 ± 3.3 in 2001 and 4.7 ± 3.4 in 2002 (P = .297).
Predictors of survival
Univariate analysis
Table 5 outlines numerous variables that were evaluated for their impact on bridging to transplant success using univariate analysis. Significant risk factors adversely affecting survival included female gender (P = .001), etiology of heart failure (CAD: P = .044; ICM: P = .003; other: P = .048), duration of LVAD support (P < .001), and LVAD score (P < .001). Additionally, there was a trend toward significance for advanced age (P = .080) and pocket infections (P = .095).
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Discussion |
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TopAbstractPatients and methodsResultsDiscussionReferences |
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Improvements in bridge to transplant success and posttransplant survival occurred along with concomitant temporal changes in device designs. We believe the reasons for improvement in these outcome variables are multifactorial and cannot be attributed to changes in device design alone. Over the last 12 years, there have been numerous improvements in patient selection, surgical techniques, treatments for right ventricular (RV) dysfunction, establishment of intraoperative hemostasis, and pre- and postoperative intensive care unit care. As it would be nearly impossible to quantify the exact contribution of each of these individual advancements to the progressive improvement in outcome over the last 12 years, we would like to highlight several of the preoperative, intraoperative, and postoperative factors that we believe have most significantly impacted outcome in patients undergoing implantation of an LVAD as a bridge to transplant (Table 7).
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Optimizing fluid balance by promoting diuresis with the use of diuretics and early institution of continuous veno-venous hemofiltration (CVVH), as well as enhancing renal perfusion with the use of an intra-aortic balloon pump, can optimize RV function. Although we currently lack objective, intrainstitutional data, we believe that optimizing a patient's preoperative fluid status decreases the incidence of postoperative RV dysfunction.
Improvements in intraoperative clinical practices have centered around 3 areas: RV function after LVAD implantation, decreased bleeding as a result of refined surgical techniques, and the use of aprotinin, as well as prophylaxis against infections with topical antibiotic placed around the preperitoneal LVAD pocket.
LVAD support induces a variety of hemodynamic changes with resulting effects on RV function.17,18 RV failure refractory to maximal pharmacological therapy occurs in 20% to 40% of patients supported with an LVAD.17,18 Though the use of inotropes and vasodilators may be successful, their effectiveness is limited because they concomitantly increase the incidence of cardiac arrhythmias, systemic hypotension, and derangement of alveolar gas exchange. Early in our experience, we performed a randomized, double-blind trial of inhaled nitric oxide (NO) in LVAD recipients with pulmonary hypertension.19 Patients randomized to receive inhaled NO demonstrated a significant reduction in pulmonary vascular resistance (PVR), along with increased LVAD output.19 Patients receiving placebo did not show a significant response but demonstrated impressive hemodynamic improvement when crossed over to the inhaled NO group.19 Prior to the widespread availability of inhaled NO at our institution, 4 of 19 LVAD recipients with RV failure required RVAD support with an associated mortality of 50%.18 However, more recently, in an analysis of 69 LVAD recipients, although the incidence of RV failure was 30%, RV mechanical support was required in only 1 patient.18 Though this study did not focus on the use of NO, more than half the recipients received NO perioperatively. More than 65% of patients who received NO avoided the need for an RVAD. This indicates that the use of NO may have contributed to the decreased incidence of RV failure. It is important to note that concomitant preoperative measures to reduce volume overload (such as CVVH), avoidance of excessive transfusions, and administration of phosphodiesterase inhibitors are also important in preventing and treating RV failure. Despite overall improvements in the management of RV failure, the ability to consistently predict the development of RV failure in LVAD recipients is still lacking. This knowledge will be of greater importance as the use of LVADs for destination therapy increases.
In our early experience, bleeding was a major limiting factor in the successful use of an LVAD as a bridge to transplant. Intraoperative and postoperative requirements for extensive blood product usage leads to a cytokine-mediated increase in PVR, with resulting adverse effects on RV function. We performed a retrospective multicenter analysis that demonstrated aprotinin to be associated with a significant decrease in postoperative blood loss and transfusion requirements.20 Additionally, aprotinin recipients demonstrated an approximate 50% reduction in postoperative requirement for an RVAD, as well as a significant reduction in mortality.20 We have since used aprotinin routinely in all patients undergoing LVAD implantation.
Refinements in the operative technique for LVAD implantation have also reduced the degree of postoperative bleeding. One of the most common sites for bleeding to occur is at the anastomosis between the left ventricle outflow tract and the aorta. In 2001, we modified our surgical technique for implanting LVADs to evert the suture line to provide enhanced tissue approximation, as previously described.21 BioGlue (Cryolife, Kennesaw, Ga) is then generously applied over the aortic outflow graft anastomosis.21
Another improvement in intraoperative practice has been the prophylactic use of vancomycin paste around the preperitoneal pocket during LVAD implantation.22 Since incorporating this into our practice a few years ago, we have noticed a decreased incidence of pocket infections (within SLVE patients).22
Treatment of vasodilatory hypotension in patients with vasodilatory shock has also improved over the years with the usage of arginine vasopressin.23,24 The vasoconstrictive effect of arginine vasopressin reduces the dependence on catecholamines, such as dopamine and epinephrine, which has the potential to increase arrhythmogenicity of myocardial tissue in patients who are already prone to develop malignant ventricular arrhythmias. An additional benefit of vasopressin involves its effect on the kidneys. Possibly due to selective constriction of the efferent arteriole (without constriction of the afferent arteriole), vasopressin increases urine output in patients with septic shock.24
Although the development of circulating antibodies, termed "sensitization," does not impact early perioperative LVAD morbidity and mortality, it has significant adverse long-term effects.25,26 LVAD recipients have prominent B-cell activation, as evidenced by heightened production of anti-human leukocyte antigen class I and II immunoglobulin G antibodies.26 As a result of these circulating antibodies, LVAD recipients are subject to repeated positive cross-matches, increased waiting time to cardiac transplant (with the risk of increased waiting list mortality), and increased risk of cellular rejection after transplantation.25 We previously reported that 66% of Thoratec HeartMate LVAD recipients at our institution were sensitized.27 Early in our experience (1992-1996), we noted the development and subsequent deleterious effects of sensitization in LVAD recipients. We therefore devised and instituted a treatment regimen consisting of cyclophosphamide and intravenous immunoglobulin for all sensitized patients beginning in 1997. The use of this immunomodulatory therapy reduced both the waiting time and risk of acute rejection in sensitized recipients.27 Because of the increased frequency of sensitization among Thoratec HeartMate LVAD recipients, it is important that panel-reactive antibody testing be performed at regular intervals. It has been suggested that sensitized patients may be at risk for the development of anti-human leukocyte antigen antibodies in the posttransplant period, thereby potentially contributing to deleterious effects on the cardiac allograft. Thus, these patients may merit closer follow-up and more targeted immunosuppression.
The HeartMate Thoratec is the preferred device at our institution for long-term support as a bridge to transplantation. Its advantages include portability and mobility, along with lower cost of support by allowing patients to be discharged from the hospital.28 Additionally, long-term anticoagulation is not required with the HeartMate, although it is possible that with judicious use of postoperative anticoagulation, the incidence of CVAs and TIAs may be decreased. This, however, requires further analysis in a randomized trial. Design improvements that have contributed to better device performance include transformation to a single percutaneous lead, outflow graft bend relief, a smaller and more flexible percutaneous cable, additional inflow valve anchoring sutures, and the Opti-Fill software.3
The main limitations to the HeartMate device, however, is that it is a univentricular support system and requires cardiopulmonary bypass for insertion as inflow must originate from the left ventricular apex. Its application is also limited in small-sized patients (body surface area < 1.5 m2) secondary to size requirements of the device, where other devices may be considered.29,30
Limitations of this study include those related to a retrospectively performed analysis. Clinical data were obtained by chart review, which has inherent limitations, such as access and accuracy of the data. Additionally, as a retrospective observational study, it is subject to selection bias and incomplete data collection. Finally, extrapolation of the results regarding improved success in bridging patients to transplant and posttransplant survival with the HeartMate is limited because of interinstitutional variability in clinical practice.
In conclusion, although the paradigm for assist devices may shift to a bridge to recovery or destination therapy, the role of an LVAD as a bridge to transplantation for patients with end-stage heart failure will remain an important one.31-33 In reviewing our institutional experience, we noted progressive improvements in bridging to transplantation success and posttransplant survival. Improvements in these outcome measures over the last 12 years occurred as a result of improved patient selection as well as many major advances in preoperative, intraoperative, and postoperative clinical practices. During this time period, there were also temporal improvements in device design. Our challenge is to continue to improve upon patient selection and perioperative management, as well to design smaller, infection-resistant, more durable devices to make LVADs increasingly more effective in bridging patients with end-stage heart failure to transplantation.
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Acknowledgments |
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References |
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