Left ventricular assist devices (LVAD) have been demonstrated

Size: px

Start display at page:

Download "Left ventricular assist devices (LVAD) have been demonstrated"

Piers Francis
5 years ago
Views:

1 Is Severe Right Ventricular Failure in Left Ventricular Assist Device Recipients a Risk Factor for Unsuccessful Bridging to Transplant and Post-Transplant Mortality Jeffrey A. Morgan, MD, Ranjit John, MD, Brian J. Lee, BA, Mehmet C. Oz, MD, and Yoshifumi Naka, MD, PhD Department of Surgery, Division of Cardiothoracic Surgery, College of Physicians and Surgeons, Columbia University, New York, New York Background. Bridging to transplant with a left ventricular assist device (LVAD) can be limited by severe right ventricular failure (RVF). The focus of this study was to ascertain whether early implantation (< 24 hours) of a right ventricular assist device (RVAD) in patients with severe RVF improved survival and whether severe RVF adversely affected post-transplant survival. Methods. We conducted a 10-year review of our bridge to transplant experience using the Heartmate device (Thoratec, Pleasanton, CA, USA), studying patients who required an Abiomed RVAD (Abiomed, Danvers, MA, USA). Results. There were 243 patients who underwent LVAD implantation, of which 17 (7.0%) required an RVAD. Ten patients underwent early RVAD insertion (< 24 hours) while 7 underwent delayed insertion (> 24 hours). Bridging to transplant was successful in 11 (64.7%) RVAD patients versus 163 (72.1%) non-rvad patients (p 0.046). Of the 10 patients who underwent early RVAD insertion, 7 (70.0%) were successfully bridged. Of the 7 patients who underwent delayed RVAD insertion, 4 (57.1%) were successfully bridged (p < 0.001). There was no significant difference in posttransplant 1, 5, and 10-year survival between RVAD and non-rvad patients (71.4%, 71.4%, and 71.4% for RVAD patients, vs 90.5%, 80.4%, and 78.5%, respectively, for non-rvad patients; p 0.366). Pretransplant RVAD support was not a risk factor for post-transplant mortality (p 0.864). Conclusions. Severe RVF adversely impacted bridging to transplant, although survival was improved with early RVAD insertion. The trend toward worse post-transplant survival in the RVAD cohort raises the possibility that if additional patients were evaluated, a difference in survival might be observed, suggesting the need for a multicenter analysis. (Ann Thorac Surg 2004;77:859 63) 2004 by The Society of Thoracic Surgeons Left ventricular assist devices (LVAD) have been demonstrated to be effective in bridging patients with end-stage heart failure to transplantation [1, 2]. However, successful bridging can be limited by development of right ventricular failure (RVF) [3, 4]. Severe RVF, requiring insertion of a right ventricular assist device (RVAD), has been demonstrated to adversely affect successful bridging to transplant, increase device-related morbidity, prolong hospital stay, and increase overall hospital cost [5, 6]. Several series have reported preoperative risk factors for development of RVF in patients with implantable LVADs [7 9]. Ochiai and colleagues [7] concluded that preoperative circulatory support, female gender, and nonischemic etiology of heart failure were significant predictors of RVF. Other series have demonstrated low pulmonary artery pressure (PAP) and low RV stroke Accepted for publication Sept 10, Address reprint requests to Dr Morgan, Columbia University, College of Physicians and Surgeons, 177 Fort Washington Ave, Milstein Hospital 7GN-435, New York, NY 10032; jm2240@columbia.edu. work index (SWI) to be significant risk factors for RVF [8]. The focus of this study was to ascertain whether development of severe RVF, requiring insertion of an RVAD, adversely affected bridging to transplant and posttransplant survival. Additionally, we sought to examine the issue of timing of RVAD insertion. Does early insertion of the RVAD improve survival? Patients and Methods Retrospectively, we reviewed our experience at Columbia Presbyterian Medical Center with bridge to transplant patients from February 1993 through February During this time period, 243 patients with end-stage heart failure underwent implantation of a Heartmate LVAD as a bridge to transplant (Thoratec, Pleasanton, CA, USA). Of these 243 patients, 17 (7.0%) developed severe RVF, requiring insertion of an Abiomed RVAD (Abiomed, Danvers, MA, USA). The definition of severe RVF and the indications for implantation of an RVAD are outlined in Table 1. Primary endpoints that were com by The Society of Thoracic Surgeons /04/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 860 MORGAN ET AL Ann Thorac Surg IMPACT OF RIGHT VENTRICULAR FAILURE ON POST-TRANSPLANT SURVIVAL 2004;77: Table 1. Definition of Severe RVF and Indications for Insertion of RVAD Maximal inotropic support Dobutamine mcg/kg/min Milrinone 0.75 mcg/kg/min Use of nitric oxide and/or prostaglandin Hemodynamic Criteria Increased CVP Decreased PAP Decreased LVAD flow (CI 2.4 L/min) Echocardiographic findings RV size and function MSOF Renal failure Decreased UO Respiratory failure Requiring high FIO2 CVP central venous pressure; FIO2 fraction of inspired oxygen; LVAD left ventricular assist device; MSOF multisystem organ failure; PAP pulmonary artery pressure; RVAD right ventricular assist device; RVF right ventricular failure; UO urine output. paratively evaluated in RVAD and non-rvad patients included successful bridging to transplant and posttransplant survival at 1, 5, and 10 years. We excluded patients who underwent a planned BIVAD insertion for biventricular failure (n 41). Statistical Analysis Data were represented as frequency distributions and percentages. Continuous variables were expressed as a mean standard deviation (SD) and were compared using independent samples t tests. Categorical variables were compared by means of 2 tests. For all analyses, a p value of less than 0.05 was considered statistically significant. Kaplan-Meier analysis was used to calculate survival along with a log-rank p value when comparing groups. Actuarial post-transplant survival at 1, 5, and 10 years was calculated by constructing life tables. The requirement for pretransplant RVAD support was evaluated using multivariate Cox proportional hazard models to ascertain whether it was a significant, independent risk factor for mortality. All data were analyzed utilizing SPSS 11.5 (SPSS Inc, Chicago, IL). Results Clinical Demographics Clinical demographics are outlined in Table 2. Age, gender, and race distribution were similar for RVAD and non-rvad patients (p NS). Additionally, etiology of heart failure was similar for both groups (p NS), with coronary artery disease (CAD) the most frequent etiology (n 138, 56.8%). A significantly increased number of patients in the RVAD group required preoperative ventilation (p 0.042). Although more patients in the RVAD group required preoperative intraaortic balloon pumps (IABPs) and had previous cardiac surgery, the difference was not statistically significant (p NS). LVAD Implantation Screening Scale Preimplantation LVAD scores were significantly higher in patients requiring RVADs ( vs ; p 0.048) [10]. Scores for LVAD were significantly higher in early RVAD patients versus late RVAD patients ( vs ; p 0.001). Pre-LVAD Hemodynamic Data Pre-LVAD hemodynamic data for RVAD and non-rvad patients is summarized in Table 3. Right ventricular assist device patients demonstrated significantly higher central venous pressure (CVP; mm Hg vs mm Hg; p 0.044), lower systolic pulmonary artery pressure (PAP; mm Hg vs mm Hg; p 0.046), lower diastolic PAP ( mm Hg vs mm Hg; p 0.037), lower mean PAP ( mm Hg vs mm Hg; p 0.032), lower right ventricular stroke work (RVSW; mm Hg ml vs mm Hg ml; p 0.045), and lower right ventricular stroke work index (RVSWI; mm Hg ml/m 2 vs ; p 0.034). Bridging to Transplant Successful bridging to transplant occurred in 11 of 17 (64.7%) RVAD patients versus 163 (72.1%) of 226 non- RVAD patients (p 0.046). Nine of the 11 RVAD patients who were successfully bridged to transplant were weaned off their RVAD after improvements in right ventricular function. Weaning was accomplished by assessment of RV recovery using hemodynamic and echocardiographic parameters. Some patients required minimal inotropic support after successful weaning of the Table 2. Baseline Clinical Characteristics of RVAD and Non- RVAD Patients Variable RVAD No RVAD p Mean age (years) a Gender Male 14 (82.4) b 183 (81.0) Female 3 (17.6) 43 (19.0) Race Caucasian 12 (70.6) 174 (77.0) African American 4 (23.5) 35 (15.5) Other 1 (5.9) 17 (7.5) Etiology of heart failure CAD 6 (35.3) 81 (35.8) ICM 9 (52.9) 129 (57.1) Other 2 (11.8) 16 (7.1) LVAD score Preoperative mechanical 10 (58.8) 78 (34.5) ventilation Preoperative IABP 4 (23.5) 45 (18.5) Reoperation 7 (41.2) 52 (23.0) a Mean standard deviation. b Absolute number (percentage). CAD coronary artery disease; IABP intra-aortic balloon pump; ICM idiopathic cardiomyopathy; LVAD left ventricular assist device; RVAD right ventricular assist device.

3 Ann Thorac Surg MORGAN ET AL 2004;77: IMPACT OF RIGHT VENTRICULAR FAILURE ON POST-TRANSPLANT SURVIVAL Table 3. Preoperative Hemodynamic Variables of RVAD and Non-RVAD Patients Variable RVAD No RVAD p CO (L/min) a CI (L/min/m 2 ) MAP (mm Hg) CVP (mm Hg) Systolic PAP (mm Hg) Diastolic PAP (mm Hg) Mean PAP (mm Hg) Heart rate (bpm) PVR (Wood units) PVRI (Wood units m 2 ) SVR SVRI RVSW (mm Hg ml) RVSWI (mm Hg ml/m 2 ) LVSW LVSWI LVW LVWI TPG a Mean standard deviation. CI cardiac index; CO cardiac output; CVP central venous pressure; LVSW left ventricular stroke work; LVSWI left ventricular stroke work index; LVW left ventricular work; LVWI left ventricular work index; PAP pulmonary artery pressure; PVR pulmonary vascular resistance; PVRI pulmonary vascular resistance index; RVSW right ventricular stroke work; RVSWI right ventricular stroke work index; SVR systemic vascular resistance; SVRI systemic vascular resistance index; TPG transpulmonary gradient. RVAD, although the precise numbers were not available. Cause of death in the 6 (35.3%) RVAD patients who expired while on support included multisystem organ failure (n 3), stroke (n 1), respiratory failure (n 1), and arrhythmias (n 1). Median RVAD duration was 4.0 days, with a mean of (0.2 to 15.0) days. Impact of Timing of RVAD Insertion on Post-LVAD Survival Ten patients underwent early RVAD insertion (within 24 hours) while 7 patients underwent delayed RVAD insertion (after 24 hours; 5 at 24 hours, 1 at 48 hours, and 1 at 96 hours after LVAD placement). Of the 10 patients who underwent early RVAD insertion, 7 (70.0%) were successfully bridged to transplant, with 6/7 (85.7%) successfully weaned off RVAD support before transplantation. Of the 7 patients who underwent delayed RVAD insertion, 4 (57.1%) were successfully bridged to transplant (p 0.001), with 3/4 (75.0%) patients successfully weaned off RVAD support before transplantation. Other Factors Affecting Successful Bridging to Transplant Recently, we reported our experience over the last 12 years using LVADs as a bridge to transplant [11]. Using univariate analysis, significant risk factors adversely affecting survival included female gender (p 0.001), etiology of heart failure (coronary artery disease [CAD], p 0.044; ischemic cardiomyopathy [ICM], p 0.003; other, p 0.048), duration of LVAD support (p 0.001), and LVAD score (p 0.001). Additionally, there was a trend toward significance for advanced age (p 0.080) and pocket infections (p 0.095). Using multivariate, stepwise logistic regression analysis, only the LVAD score was a significant predictor of survival to transplant (OR 1.214, 95% CI to 1.316, p 0.001, SE 0.041). Bridging to transplant was successful in 88.6% of lowscoring (scores of 1 to 4) patients, 64.5% of mediumscoring [5 7] patients, and 48.9% of high-scoring [8 10] patients (p 0.001). Post-Transplant Survival Actuarial survival at 1, 5, and 10 years post-transplant was 71.4%, 71.4%, and 71.4% for the RVAD group, versus 90.5%, 80.4%, and 78.5% for the non-rvad group (p 0.366) (Fig 1). Although actuarial survival was higher for the non-rvad group at each time point, the differences were not statistically significant (p NS). There was no significant difference in post-transplant survival between those patients who underwent early insertion of the RVAD ( 24 hours) versus delayed insertion ( 24 hours) (p NS). Evaluation of Pre-Transplant RVAD in Multivariate, Cox Proportional Hazard Models Using multivariate, Cox proportional hazard models, pretransplant RVAD support was not a statistically significant risk factor for post-transplant mortality (OR 0.646, 95% confidence interval [CI] to 0.972, p 0.864, SE 0.142).

862 MORGAN ET AL Ann Thorac Surg IMPACT OF RIGHT VENTRICULAR FAILURE ON POST-TRANSPLANT SURVIVAL 2004;77:859 63 Fig 1.

4 862 MORGAN ET AL Ann Thorac Surg IMPACT OF RIGHT VENTRICULAR FAILURE ON POST-TRANSPLANT SURVIVAL 2004;77: Fig 1. Actuarial post-transplant survival for patients supported with RVAD versus those patients without severe right ventricular failure. (RVAD right ventricular assist device.) Comment Ventricular assist devices have contributed immensely to the management of patients with end-stage heart failure [12 14]. Patients bridged to transplant using LVADs have demonstrated improvements in blood pressure, hepatic function, renal function, physical function, and quality of life [12, 14]. This can be accomplished without adversely affecting post-transplant survival [15]. However, two major limiting factors to further success with LVADs have been right ventricular dysfunction and device-related complications, such as thromboembolism, infection, and bleeding. Depending on the preexisting condition of the right ventricle, an LVAD may have a beneficial effect by reducing afterload, or a detrimental effect by increasing preload to an already-compromised RV, due to cardiomyopathy, ischemia, arrhythmias, or pulmonary hypertension. Although the incidence of post-lvad RV failure has decreased with improved patient selection (such as BIVAD use for biventricular failure), use of nitric oxide, phosphodiesterase inhibitors, and reduction of postoperative bleeding with the use of the serine protease inhibitor aprotonin, it is still a major contributor of post-lvad morbidity and prolonged length of hospital stay [16, 17]. To maximize the likelihood of a patient with post- LVAD RV failure being successfully bridged to transplantation, we have devised an algorithm for the evaluation of RV dysfunction after implantation of an LVAD (Fig 2). We believe that severe RV dysfunction(failure) should be treated with early implantation of an RVAD. Patients are anticoagulated after RVAD insertion but only after there is evidence that bleeding has ceased. Early RVAD insertion can limit progression to significant, potentially irreversible multisystem organ failure (MSOF). This is not to suggest that trials with more conservative therapies, such as nitric oxide and milrinone, should not be attempted. However, careful observation of the overall clinical picture beginning in the operating room is essential, with strong consideration of early RVAD insertion. Patients who initially require biventricular support constitute a different patient population than patients who undergo LVAD implantation followed by insertion of an RVAD after subsequent development of severe right ventricular failure. Biventricular assist device patients generally have more profound multiorgan dysfunction initially than patients requiring univentricular support. In these patients, CVPs tend to be higher, PAPs lower, and there is an increased association with biventricular arrhythmias. Therefore, we did not compare these two heterogeneous groups of patients. Deciding between a univentricular and a biventricular support system, however, can often be challenging, with only few definitive criteria for guidance in making the decision [7 9]. Rather than focusing on individual hemodynamic values, a patient s overall clinical picture should guide the decision [18]. Additionally, specific clinical factors that have been suggested to favor biventricular support include biventricular infarction, lethal arrhythmias, low ( 15%) RV ejection fraction and large RV volumes, elevated fixed pulmonary vascular resistance, and hepatic dysfunction [18]. Our challenge is to be more selective in implanting LVADs to minimize RVF and the need for RVAD insertion. In patients who clearly require biventricular support, isolated LVAD implantation should be avoided. However, the decision between the need for univentricular versus biventricular support remains controversial and requires further analysis. This is particularly important in patients who are being considered for LVADs as destination therapy. In this patient population, it is prudent to consider predictors of RVF in establishing exclusion criteria for LVAD placement. Patients who would be excluded would include those patients who are high risk Fig 2. Algorithm for assessment of RV failure after insertion of an LVAD. (ICU intensive care unit; LVAD left ventricular assist device; NO nitric oxide; OR operating room; RV right ventricle; RVAD right ventricular assist device.)

5 Ann Thorac Surg MORGAN ET AL 2004;77: IMPACT OF RIGHT VENTRICULAR FAILURE ON POST-TRANSPLANT SURVIVAL for development of right ventricular failure while on left ventricular support. Limitations of this study include those related to a retrospectively performed analysis. Data were obtained by chart review, which has inherent limitations such as access and accuracy of the data. Additionally, the number of patients in the RVAD group (17 implanted, 11 successfully bridged to transplant) was relatively low, limiting statistical power. Although we demonstrated no statistically significant difference in post-transplant survival between RVAD and non-rvad patients, a trend toward worse survival in the group of patients that required RVAD support raises the possibility that if a larger cohort of patients with severe RVF requiring insertion of an RVAD was studied by conducting a multi-institutional analysis, a statistically significant difference in survival might be observed. Additionally, patients with clinically significant RV failure (not requiring RVAD) were not evaluated in this study. It is important to note that these patients probably constitute the majority of patients with RV dysfunction after LVAD insertion. Furthermore, late RVAD insertion could not be evaluated in multivariate analysis as a potential independent predictor of adverse outcome due to limitations regarding sample size. Finally, it is possible that the worse survival in the delayed group was due to those patients being sicker, although, anecdotally, this did not seem to be the case. In conclusion, we believe that RVAD insertion should be performed early after the development of severe RV failure after LVAD implantation, and that RVAD support should be continued for an adequate duration to allow for RV recovery or until transplantation. It is essential that while on RVAD support, opportunities to maximally improve the patient s hemodynamic status and fluid balance, such as the use of continuous venovenous hemofiltration and dialysis, be pursued. It is important to note that while optimal timing of RVAD insertion for severe RV failure after LVAD implantation has yet to be clearly defined, a low threshold for early RVAD insertion may be preferable to subsequent development of multisystem organ failure that could potentially develop with a more conservative approach. Fortunately, the incidence of severe RVF requiring an RVAD after insertion of an LVAD in the current era is relatively low. Therefore, even in a single center large experience, the number of such patients is too low to allow for the traditional complete statistical analysis with substantial power. Nevertheless, we believe that our experience highlights the importance of this major complication after LVAD implantation, especially with the increased use of LVADs as destination therapy. Additionally, with several new heart support devices available, an improved understanding of interventricular interactions, as well as the pathophysiology of RV dysfunction after left heart support, is essential to further success in the treatment of patients with end-stage heart failure. Dr Yoshifumi Naka is Herbert Irving Assistant Professor of Surgery at Columbia University, College of Physicians and Surgeons. References Peterze B, Lonn U, Jansson K, Rutberg H, Casimir-Ahn H, Nylander E. Long-term follow-up of patients treated with an implantable left ventricular assist device as an extended bridge to heart transplantation. J Heart Lung Transplant 2002;21: Pennington DG, McBride LR, Peigh PS, Miller LW, Swartz MT. Eight years experience with bridging to cardiac transplantation. J Thorac Cardiovasc Surg 1994;107: Farrar DJ, Compton PG, Hershon JJ, Fonger JD, Hill JD. Right heart interaction with the mechanically assisted left heart. World J Surg 1985;9: McCarthy PM, Savage RM, Fraser CD, et al. Hemodynamic and physiologic changes during support with an implantable left ventricular assist device. J Thorac Cardiovasc Surg 1995;109: Kavarana MN, Pessin-Minsley MS, Urtecho J, et al. Right ventricular dysfunction and organ failure in left ventricular assist device recipients: a continuing problem. Ann Thorac Surg 2002;73: Slater JP, Rose EA, Levin HR, et al. Low thromboembolic risk without anticoagulation using advanced-design left ventricular assist devices. Ann Thorac Surg 1996;62: Ochiai Y, McCarthy PM, Smedira NG, et al. Predictors of severe right ventricular failure after implantable left ventricular assist device insertion: analysis of 245 patients. Circulation 2002;106(Suppl 1):I Fukamachi K, McCarthy PM, Smedira NG, Vargo RL, Starling RC, Young JB. Preoperative risk factors for right ventricular failure after implantable left ventricular assist device insertion. Ann Thorac Surg 1999;68: Nakatani S, Thomas JD, Savage RM, Vargo RL, Smedira NG, McCarthy PM. Prediction of right ventricular dysfunction after left ventricular assist device implantation. Circulation 1996;94(Suppl):II Rao V, Oz MC, Flannery MA, Catanese KA, Argenziano M, Naka Y. Revised screening scale to predict survival after insertion of a left ventricular assist device. J Thorac Cardiovasc Surg 2003;125: Morgan JA, John R, Rao V, et al. Bridging to transplant with the Heartmate left ventricular assist device: the Columbia Presbyterian twelve-year experience. In-press, J Thorac Cardiovasc Surg. 12. Sun BC, Catanese KA, Spanier TB, et al. 100 long-term implantable left ventricular assist devices: the Columbia Presbyterian interim experience. Ann Thorac Surg 1999;68: Morales DL, Catanese KA, Helman DN, et al. Six-year experience of caring for forty-four patients with a left ventricular assist device at home: safe, economical, necessary. J Thorac Cardiovasc Surg 2000;119: Oz MC, Goldstein DJ, Pepino P, et al. Screening scale predicts patients successfully receiving long-term implantable left ventricular assist devices. Circulation 1995;92: Morgan JA, Park Y, Kherani AR, et al. Does bridging to transplant with a left ventricular assist device adversely affect post-transplant survival? A comparative analysis of mechanical versus inotropic support. J Thorac Cardiovasc Surg 2003;126: Chen JM, Levin HR, Rose EA, et al. Experience with right ventricular assist devices for perioperative right-sided circulatory failure. Ann Thorac Surg 1996;61: Farrar DJ, Hill DJ, Pennington DG, et al. Preoperative and postoperative comparison of patients with univentricular and biventricular support with the Thoratec ventricular assist device as a bridge to cardiac transplantation. J Thorac Cardiovasc Surg 1997;113: Kormos RL, Gasior TA, Kawai A, et al. Transplant candidate s clinical status rather than right ventricular function defines need for univentricular versus biventricular support. J Thorac Cardiovasc Surg 1996;111:

Predictors of Severe Right Ventricular Failure After Implantable Left Ventricular Assist Device Insertion: Analysis of 245 Patients

Predictors of Severe Right Ventricular Failure After Implantable Left Ventricular Assist Device Insertion: Analysis of 245 Patients Yoshie Ochiai, MD; Patrick M. McCarthy, MD; Nicholas G. Smedira, MD;