ASAIO Journal 2015
Adult Circulatory Support
Outcomes of Patients with Right Ventricular Failure on Milrinone After Left Ventricular Assist Device Implantation Athanasios Tsiouris,* Gaetano Paone,† Robert J. Brewer,† Hassan W. Nemeh,† Jamil Borgi,† and Jeffrey A. Morgan†
Previous studies have grouped together both patients requiring right ventricular assist devices (RVADs) with patients requiring prolonged milrinone therapy after left ventricular assist device (LVAD) implantation. We retrospectively identified 149 patients receiving LVADs and 18 (12.1%) of which developed right ventricular (RV) failure. We then separated these patients into those requiring RVADs versus prolonged milrinone therapy. This included 10 patients who were treated with prolonged milrinone and eight patients who underwent RVAD placement. Overall, the RV failure group had worse survival compared with the non-RV failure cohort (p = 0.038). However, this was only for the subgroup of patients who required RVADs, who had a 1, 6, 12, and 24 month survival of 62.5%, 37.5%, 37.5%, and 37.5%, respectively, versus 96.8%, 92.1%, 86.7%, and 84.4% for patients without RV failure (p < 0.001). Patients treated with prolonged milrinone therapy for RV failure had similar survivals compared with patients without RV failure. In the RV failure group, age, preoperative renal failure, and previous cardiac surgery were predictors of the need for prolonged postoperative milrinone. As LVADs become a more widely used therapy for patients with refractory, end-stage heart failure, it will be important to reduce the incidence of RV failure, as it yields significant morbidity and increases cost. ASAIO Journal 2015; 61:133–138.
with those patients requiring prolonged milrinone therapy.6–11 The goal of our study was to separate out these two groups of patients with RV failure and analyze outcomes in each subgroup independently. Methods This retrospective study was approved by the Henry Ford Health System’s Institutional Review Board. We reviewed our institutions’ LVAD dataset and analyzed patients who underwent CF LVAD implantation as a bridge to transplantation (BTT) or destination therapy (DT) from March 2006 until July 2013. One hundred and forty-nine patients were identified and formed the cohort of this study. They received either HeartMate II (n = 136; Thoratec Corp., Pleasanton, California) or Heartware (n = 13; HeartWare Inc., Framingham, Massachusetts) LVADs. Patients with RV failure were identified with RV failure defined as the need for intravenous inotropes for greater than 14 days postoperatively or patients who underwent implantation of a RVAD. Outcomes of patients with RV failure were then analyzed separately based on whether they required an RVAD or prolonged milrinone therapy. A CentriMag (Thoratec co-operation, Pleasanton, California) RVAD was used in 63% (5/8), and an Abiomed (AbioMed, Danvers, Massachusetts) circulatory support system was inserted in 37% (3/8).
Key Words: left ventricular assist device, right ventricular failure, milrinone, outcomes
Device Management
Left ventricular assist devices (LVADs) are accepted therapy
Device speed was clinically adjusted to optimize flow, peripheral perfusion, organ function, and left ventricular (LV) decompression. Patients underwent periodic echocardiograms to evaluate the degree of LV decompression, aortic ejection, residual mitral regurgitation, position of the interventricular septum, RV function, and severity of tricuspid regurgitation (TR). All patients were postoperatively anticoagulated on aspirin 81 mg daily (325 mg for patients receiving HeartWare LVAD) and warfarin with a target international normalized ratio (INR) of 1.8–2.5. Heart failure medications typically included a β-blocker, ace inhibitor, and diuretics, as well as Sildenafil if they had significant residual pulmonary hypertension (HTN).
for patients with refractory, end-stage heart failure. Continuous-flow (CF) pumps have yielded improvements in short- and long-term survival, quality of life, and a reduction in LVADrelated complications, including bleeding, infection, and device malfunctions compared with older pulsatile-flow (PF) pumps.1–5 However, right ventricular (RV) failure remains an important complication of LVAD therapy and a significant contributor to postoperative morbidity and mortality.6–10 Previous studies that have investigated the effect of postLVAD RV failure on survival, however, grouped together both patients requiring right ventricular assist devices (RVADs)
Patient Data From the *Section of Cardiac Surgery, Yale School of Medicine, New Haven, Connecticut; and †Division of Cardiac Surgery, Henry Ford Hospital, Detroit, Michigan. Submitted for consideration April 2014; accepted for publication in revised form November 2014. Disclosure: The authors have no conflicts of interest to report. Correspondence: Athanasios Tsiouris, MD, Section of Cardiac Surgery, Yale School of Medicine, 330 Cedar St, Boardman 204, New Haven, CT 06510. Email: [email protected] Copyright © 2014 by the American Society for Artificial Internal Organs
Patient demographics included age, gender, race, body surface area (BSA), body mass index, previous sternotomy, days in hospital before LVAD implantation, preoperative creatinine, liver function tests and associated comorbidities—HTN, diabetes mellitus, chronic renal insufficiency, dialysis, chronic obstructive pulmonary disease, and peripheral vascular disease. Chronic renal insufficiency was defined as glomerular filtration rate (GFR) 14 days since implantation), and 7% (33/484) required late inotropic support (inotropes starting 14 days after implantation). They reported an improved 12 month survival for the non-RV failure group (79%) compared with patients who received an RVAD (59%, p = 0.004) or extended inotropes (56%, p = 0.007), whereas there was no difference for the cohort who received late inotropes (75%, p = 0.81). They also demonstrated that length of hospital stay for non-RV failure patients was significantly shorter (22 days) compared with RVAD patients (32 days), extended inotropic support (35 days),
Table 4. Univariate Association of Patient Demographics/ Comorbidities, Preoperative Hemodynamic Measurements, and Operative Characteristics Between Milrinone and RVAD Groups Variable Age Female Male African American Caucasian BSA BMI Albumin pre-VAD BTT DT DM HTN Dialysis COPD PVD Vented AST pre-VAD ALT pre-VAD Creatinine pre-VAD CPB time XCl time MCS at time of VAD On inotropes at time of VAD Pre-VAD CVP Pre-VAD PAPs Pre-VAD PAPd Pre-VAD CI Pre-VAD PCWP ICM NICM Previous cardiac surgery
137
MILRINONE FOR RV FAILURE AFTER LVAD
Milrinone (n = 10)
RVAD (n = 8)
47.3 ± 13.4 3 (30%) 7 (70%) 5 (50%) 5 (50%) 2.0 ± 0.4 27.5 ± 6.2 3.3 ± 0.4 5 (50%) 5 (50%) 2 (20%) 8 (80%) 0 (0%) 2 (20%) 1 (10%) 2 (20%) 27.5 ± 8.8 43.2 ± 70.6 1.4 ± 0.5 140.6 ± 43.4 30.7 ± 37.5 3 (30%) 10 (100%) 13.5 ± 6.9 54.5 ± 13.6 26.4 ± 6.8 2.2 ± 0.8 26.5 ± 6.1 2 (20%) 8 (80%) 0 (0%)
57.8 ± 8.9 1 (13%) 7 (88%) 2 (25%) 6 (75%) 2.0 ± 0.3 28.9 ± 6.1 3.1 ± 0.3 5 (63%) 3 (38%) 3 (38%) 7 (88%) 3 (38%) 2 (25%) 3 (38%) 3 (38%) 106.0 ± 225.2 37.4 ± 38.9 2.1 ± 0.9 161.0 ± 74.0 6.5 ± 18.4 3 (38%) 7 (88%) 11.0 ± 5.1 52.7 ± 9.7 22.0 ± 5.9 2.1 ± 0.7 24.4 ± 4.3 4 (50%) 4 (50%) 4 (50%)
p 0.05 0.588 0.367 0.740 0.813 0.130 0.664 0.608 1.000 0.038 1.000 0.275 0.608 0.793 0.600 0.043 1.000 0.140 1.000 0.444 0.532 0.595 0.251 0.896 0.566 0.321 0.023
ALT, alanine aminotransferase; AST, aspartate transaminase; BMI, body mass index; BSA, body surface area; BTT, bridge to transplant; CI, cardiac index; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; CVP, central venous pressure; DM, diabetes mellitus; DT, destination therapy; HTN, hypertension; ICM, ischemic cardiomyopathy; MCS, mechanical circulatory support; NICM, non-ischemic cardiomyopathy; PAPd, pulmonary artery diastolic pressure; PAPs, pulmonary artery systolic pressure; PCWP, pulmonary capillary wedge pressure; PVD, peripheral vascular disease; RVAD, right ventricular assist devices; XCl, cross clamp.
and delayed inotropic support (32 days) (p < 0.001). This study showed that survival for non-RV failure patients and patients who received late inotropic support is similar (79% vs. 75%, p = 0.81), which is consistent with our analysis. They did demonstrate, though, similar poor survival between patients with RVAD and patients with prolonged inotropic support. In our study, we did not separately analyze patients with prolonged inotropic support. Looking at the characteristics of the prolonged inotropic support cohort in the study by Kormos et al.,10 these patients were not that different from the RVAD patients (CVP, PCWP, renal function), and this is potential explanation why patients on prolonged inotropes had similar dismal survival with patients receiving RVADs. In addition, the study by Kormos et al.,10 enrolled HMII patients up until 2008. Significant advances and a lot have been learned over the recent years on how to manage RV failure in LVAD patients. Our recently increased awareness for preventing and treating post-LVAD RV, by means of preoperative optimization, more aggressive
diuresis, proper pump positioning in the LV, and avoidance of overzealous product transfusion which increases RV loading and pulmonary congestion, have all decreased the severity of RV failure with improved associated outcomes, especially in patients with mild RV failure. Alternatively, it could be that over the recent years, our comfort level for treating RV failure with judicious inotropic support at home has increased. This is certainly another possible explanation for differences in outcomes. Our limited statistical power is also a potential flaw. Despite improved outcomes in our milrinone cohort, we also demonstrated that patients receiving an RVAD had overall poor outcomes, with a mortality of 50%. The rest of the RVAD patients were successfully explanted (50%) and only one patient (12%) received a heart transplant. These results are analogous to outcomes published by Takeda et al.11 They reported an 11% unplanned RVAD implantation rate in 398 patients receiving a PF or CF LVAD over a 12 year period, with 49% of patients (21/44) successfully explanted. Of the 23 patients (51%) in whom the RV failed to recover, the inhospital mortality was 74% and the bridge to transplant rate was 35%. Morgan et al.24 have previously shown that severe RV failure requiring RVAD support adversely impacts bridging to transplant (72% vs. 64%; p = 0.046) and a trend toward worst posttransplant survival in their RVAD cohort. Our study has several limitations. First, it was an observational, nonrandomized study and is subject to limitations inherent to any retrospective study. Second, statistical tests may have been insufficiently powered due to our relatively small sample size. Third, there was not enough power to detect significant predictors in a multivariate model. In addition, the duration of follow-up was relatively short. Finally, it was a single institutional study and selection bias may have been introduced. In conclusion, patients with post-LVAD RV failure requiring prolonged milrinone therapy have similar survival and postoperative complications as non-RV failure LVAD patients. There also appears to be a trend toward a decreased readmission rate in patients receiving milrinone. Patients receiving RVADs after LVAD implantation continue to have substantially reduced survival, despite our large clinical experience with managing RV failure. In patients who develop RV failure, age, preoperative renal failure, and previous cardiac surgery are potential predictors of milrinone infusion. Larger studies are needed to ascertain these findings, as predicting and reducing RV failure remains a significant challenge in LVAD therapy, as it yields significant morbidity and increases cost. References 1. Slaughter MS, Pagani FD, Rogers JG, et al; HeartMate II Clinical Investigators: Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant 29(4 Suppl): S1–39, 2010. 2. Slaughter MS, Rogers JG, Milano CA, et al; HeartMate II Investigators: Advanced heart failure treated with continuousflow left ventricular assist device. N Engl J Med 361: 2241– 2251, 2009. 3. Pagani FD, Miller LW, Russell SD, et al; HeartMate II Investigators: Extended mechanical circulatory support with a continuousflow rotary left ventricular assist device. J Am Coll Cardiol 54: 312–321, 2009. 4. John R, Kamdar F, Liao K, Colvin-Adams M, Boyle A, Joyce L: Improved survival and decreasing incidence of adverse events with the HeartMate II left ventricular assist device as bridge-totransplant therapy. Ann Thorac Surg 86: 1227–1235, 2008.
138 TSIOURIS et al. 5. Miller LW, Pagani FD, Russell SD, et al; HeartMate II Clinical Investigators: Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 357: 885–896, 2007. 6. Saito S, Sakaguchi T, Miyagawa S, et al: Recovery of right heart function with temporary right ventricular assist using a centrifugal pump in patients with severe biventricular failure. J Heart Lung Transplant 31: 858–864, 2012. 7. 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 73: 745–750, 2002. 8. Furukawa K, Motomura T, Nosé Y: Right ventricular failure after left ventricular assist device implantation: The need for an implantable right ventricular assist device. Artif Organs 29: 369–377, 2005. 9. Dang NC, Topkara VK, Mercando M, et al: Right heart failure after left ventricular assist device implantation in patients with chronic congestive heart failure. J Heart Lung Transplant 25: 1–6, 2006. 10. Kormos RL, Teuteberg JJ, Pagani FD, et al; HeartMate II Clinical Investigators: Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: Incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg 139: 1316–1324, 2010. 11. Takeda K, Naka Y, Yang JA, et al: Outcome of unplanned right ventricular assist device support for severe right heart failure after implantable left ventricular assist device insertion. J Heart Lung Transplant 33: 141–148, 2014. 12. Kormos RL: The right heart failure dilemma in the era of left ventricular assist devices. J Heart Lung Transplant 33: 134–135, 2014. 13. Farrar DJ, Compton PG, Hershon JJ, Fonger JD, Hill JD: Right heart interaction with the mechanically assisted left heart. World J Surg 9: 89–102, 1985. 14. Farrar DJ: Ventricular interactions during mechanical circulatory support. Semin Thorac Cardiovasc Surg 6: 163–168, 1994.
15. Moon MR, Bolger AF, DeAnda A, et al: Septal function during left ventricular unloading. Circulation 95: 1320–1327, 1997. 16. MacGowan GA, Schueler S: Right heart failure after left ventricular assist device implantation: Early and late. Curr Opin Cardiol 27: 296–300, 2012. 17. 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 106(12 Suppl 1): I198–I202, 2002. 18. Matthews JC, Koelling TM, Pagani FD, Aaronson KD: The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates. J Am Coll Cardiol 51: 2163–2172, 2008. 19. Borgi J, Tsiouris A, Hodari A, Cogan CM, Paone G, Morgan JA: Significance of postoperative acute renal failure after continuous-flow left ventricular assist device implantation. Ann Thorac Surg 95: 163–169, 2013. 20. Toma M, Starling RC: Inotropic therapy for end-stage heart failure patients. Curr Treat Options Cardiovasc Med 12: 409–419, 2010. 21. Ahmad T, Patel CB, Milano CA, Rogers JG: When the heart runs out of heartbeats: Treatment options for refractory end-stage heart failure. Circulation 125: 2948–2955, 2012. 22. Hauptman PJ, Mikolajczak P, George A, et al: Chronic inotropic therapy in end-stage heart failure. Am Heart J 152: 1096.e1– 1096.e8, 2006. 23. Upadya S, Lee FA, Saldarriaga C, et al: Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure. J Heart Lung Transplant 23: 466–472, 2004. 24. Morgan JA, John R, Lee BJ, Oz MC, Naka Y: Is severe right ventricular failure in left ventricular assist device recipients a risk factor for unsuccessful bridging to transplant and post-transplant mortality. Ann Thorac Surg 77: 859–863, 2004.
Adult Circulatory Support
Outcomes of Patients with Right Ventricular Failure on Milrinone After Left Ventricular Assist Device Implantation Athanasios Tsiouris,* Gaetano Paone,† Robert J. Brewer,† Hassan W. Nemeh,† Jamil Borgi,† and Jeffrey A. Morgan†
Previous studies have grouped together both patients requiring right ventricular assist devices (RVADs) with patients requiring prolonged milrinone therapy after left ventricular assist device (LVAD) implantation. We retrospectively identified 149 patients receiving LVADs and 18 (12.1%) of which developed right ventricular (RV) failure. We then separated these patients into those requiring RVADs versus prolonged milrinone therapy. This included 10 patients who were treated with prolonged milrinone and eight patients who underwent RVAD placement. Overall, the RV failure group had worse survival compared with the non-RV failure cohort (p = 0.038). However, this was only for the subgroup of patients who required RVADs, who had a 1, 6, 12, and 24 month survival of 62.5%, 37.5%, 37.5%, and 37.5%, respectively, versus 96.8%, 92.1%, 86.7%, and 84.4% for patients without RV failure (p < 0.001). Patients treated with prolonged milrinone therapy for RV failure had similar survivals compared with patients without RV failure. In the RV failure group, age, preoperative renal failure, and previous cardiac surgery were predictors of the need for prolonged postoperative milrinone. As LVADs become a more widely used therapy for patients with refractory, end-stage heart failure, it will be important to reduce the incidence of RV failure, as it yields significant morbidity and increases cost. ASAIO Journal 2015; 61:133–138.
with those patients requiring prolonged milrinone therapy.6–11 The goal of our study was to separate out these two groups of patients with RV failure and analyze outcomes in each subgroup independently. Methods This retrospective study was approved by the Henry Ford Health System’s Institutional Review Board. We reviewed our institutions’ LVAD dataset and analyzed patients who underwent CF LVAD implantation as a bridge to transplantation (BTT) or destination therapy (DT) from March 2006 until July 2013. One hundred and forty-nine patients were identified and formed the cohort of this study. They received either HeartMate II (n = 136; Thoratec Corp., Pleasanton, California) or Heartware (n = 13; HeartWare Inc., Framingham, Massachusetts) LVADs. Patients with RV failure were identified with RV failure defined as the need for intravenous inotropes for greater than 14 days postoperatively or patients who underwent implantation of a RVAD. Outcomes of patients with RV failure were then analyzed separately based on whether they required an RVAD or prolonged milrinone therapy. A CentriMag (Thoratec co-operation, Pleasanton, California) RVAD was used in 63% (5/8), and an Abiomed (AbioMed, Danvers, Massachusetts) circulatory support system was inserted in 37% (3/8).
Key Words: left ventricular assist device, right ventricular failure, milrinone, outcomes
Device Management
Left ventricular assist devices (LVADs) are accepted therapy
Device speed was clinically adjusted to optimize flow, peripheral perfusion, organ function, and left ventricular (LV) decompression. Patients underwent periodic echocardiograms to evaluate the degree of LV decompression, aortic ejection, residual mitral regurgitation, position of the interventricular septum, RV function, and severity of tricuspid regurgitation (TR). All patients were postoperatively anticoagulated on aspirin 81 mg daily (325 mg for patients receiving HeartWare LVAD) and warfarin with a target international normalized ratio (INR) of 1.8–2.5. Heart failure medications typically included a β-blocker, ace inhibitor, and diuretics, as well as Sildenafil if they had significant residual pulmonary hypertension (HTN).
for patients with refractory, end-stage heart failure. Continuous-flow (CF) pumps have yielded improvements in short- and long-term survival, quality of life, and a reduction in LVADrelated complications, including bleeding, infection, and device malfunctions compared with older pulsatile-flow (PF) pumps.1–5 However, right ventricular (RV) failure remains an important complication of LVAD therapy and a significant contributor to postoperative morbidity and mortality.6–10 Previous studies that have investigated the effect of postLVAD RV failure on survival, however, grouped together both patients requiring right ventricular assist devices (RVADs)
Patient Data From the *Section of Cardiac Surgery, Yale School of Medicine, New Haven, Connecticut; and †Division of Cardiac Surgery, Henry Ford Hospital, Detroit, Michigan. Submitted for consideration April 2014; accepted for publication in revised form November 2014. Disclosure: The authors have no conflicts of interest to report. Correspondence: Athanasios Tsiouris, MD, Section of Cardiac Surgery, Yale School of Medicine, 330 Cedar St, Boardman 204, New Haven, CT 06510. Email: [email protected] Copyright © 2014 by the American Society for Artificial Internal Organs
Patient demographics included age, gender, race, body surface area (BSA), body mass index, previous sternotomy, days in hospital before LVAD implantation, preoperative creatinine, liver function tests and associated comorbidities—HTN, diabetes mellitus, chronic renal insufficiency, dialysis, chronic obstructive pulmonary disease, and peripheral vascular disease. Chronic renal insufficiency was defined as glomerular filtration rate (GFR) 14 days since implantation), and 7% (33/484) required late inotropic support (inotropes starting 14 days after implantation). They reported an improved 12 month survival for the non-RV failure group (79%) compared with patients who received an RVAD (59%, p = 0.004) or extended inotropes (56%, p = 0.007), whereas there was no difference for the cohort who received late inotropes (75%, p = 0.81). They also demonstrated that length of hospital stay for non-RV failure patients was significantly shorter (22 days) compared with RVAD patients (32 days), extended inotropic support (35 days),
Table 4. Univariate Association of Patient Demographics/ Comorbidities, Preoperative Hemodynamic Measurements, and Operative Characteristics Between Milrinone and RVAD Groups Variable Age Female Male African American Caucasian BSA BMI Albumin pre-VAD BTT DT DM HTN Dialysis COPD PVD Vented AST pre-VAD ALT pre-VAD Creatinine pre-VAD CPB time XCl time MCS at time of VAD On inotropes at time of VAD Pre-VAD CVP Pre-VAD PAPs Pre-VAD PAPd Pre-VAD CI Pre-VAD PCWP ICM NICM Previous cardiac surgery
137
MILRINONE FOR RV FAILURE AFTER LVAD
Milrinone (n = 10)
RVAD (n = 8)
47.3 ± 13.4 3 (30%) 7 (70%) 5 (50%) 5 (50%) 2.0 ± 0.4 27.5 ± 6.2 3.3 ± 0.4 5 (50%) 5 (50%) 2 (20%) 8 (80%) 0 (0%) 2 (20%) 1 (10%) 2 (20%) 27.5 ± 8.8 43.2 ± 70.6 1.4 ± 0.5 140.6 ± 43.4 30.7 ± 37.5 3 (30%) 10 (100%) 13.5 ± 6.9 54.5 ± 13.6 26.4 ± 6.8 2.2 ± 0.8 26.5 ± 6.1 2 (20%) 8 (80%) 0 (0%)
57.8 ± 8.9 1 (13%) 7 (88%) 2 (25%) 6 (75%) 2.0 ± 0.3 28.9 ± 6.1 3.1 ± 0.3 5 (63%) 3 (38%) 3 (38%) 7 (88%) 3 (38%) 2 (25%) 3 (38%) 3 (38%) 106.0 ± 225.2 37.4 ± 38.9 2.1 ± 0.9 161.0 ± 74.0 6.5 ± 18.4 3 (38%) 7 (88%) 11.0 ± 5.1 52.7 ± 9.7 22.0 ± 5.9 2.1 ± 0.7 24.4 ± 4.3 4 (50%) 4 (50%) 4 (50%)
p 0.05 0.588 0.367 0.740 0.813 0.130 0.664 0.608 1.000 0.038 1.000 0.275 0.608 0.793 0.600 0.043 1.000 0.140 1.000 0.444 0.532 0.595 0.251 0.896 0.566 0.321 0.023
ALT, alanine aminotransferase; AST, aspartate transaminase; BMI, body mass index; BSA, body surface area; BTT, bridge to transplant; CI, cardiac index; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; CVP, central venous pressure; DM, diabetes mellitus; DT, destination therapy; HTN, hypertension; ICM, ischemic cardiomyopathy; MCS, mechanical circulatory support; NICM, non-ischemic cardiomyopathy; PAPd, pulmonary artery diastolic pressure; PAPs, pulmonary artery systolic pressure; PCWP, pulmonary capillary wedge pressure; PVD, peripheral vascular disease; RVAD, right ventricular assist devices; XCl, cross clamp.
and delayed inotropic support (32 days) (p < 0.001). This study showed that survival for non-RV failure patients and patients who received late inotropic support is similar (79% vs. 75%, p = 0.81), which is consistent with our analysis. They did demonstrate, though, similar poor survival between patients with RVAD and patients with prolonged inotropic support. In our study, we did not separately analyze patients with prolonged inotropic support. Looking at the characteristics of the prolonged inotropic support cohort in the study by Kormos et al.,10 these patients were not that different from the RVAD patients (CVP, PCWP, renal function), and this is potential explanation why patients on prolonged inotropes had similar dismal survival with patients receiving RVADs. In addition, the study by Kormos et al.,10 enrolled HMII patients up until 2008. Significant advances and a lot have been learned over the recent years on how to manage RV failure in LVAD patients. Our recently increased awareness for preventing and treating post-LVAD RV, by means of preoperative optimization, more aggressive
diuresis, proper pump positioning in the LV, and avoidance of overzealous product transfusion which increases RV loading and pulmonary congestion, have all decreased the severity of RV failure with improved associated outcomes, especially in patients with mild RV failure. Alternatively, it could be that over the recent years, our comfort level for treating RV failure with judicious inotropic support at home has increased. This is certainly another possible explanation for differences in outcomes. Our limited statistical power is also a potential flaw. Despite improved outcomes in our milrinone cohort, we also demonstrated that patients receiving an RVAD had overall poor outcomes, with a mortality of 50%. The rest of the RVAD patients were successfully explanted (50%) and only one patient (12%) received a heart transplant. These results are analogous to outcomes published by Takeda et al.11 They reported an 11% unplanned RVAD implantation rate in 398 patients receiving a PF or CF LVAD over a 12 year period, with 49% of patients (21/44) successfully explanted. Of the 23 patients (51%) in whom the RV failed to recover, the inhospital mortality was 74% and the bridge to transplant rate was 35%. Morgan et al.24 have previously shown that severe RV failure requiring RVAD support adversely impacts bridging to transplant (72% vs. 64%; p = 0.046) and a trend toward worst posttransplant survival in their RVAD cohort. Our study has several limitations. First, it was an observational, nonrandomized study and is subject to limitations inherent to any retrospective study. Second, statistical tests may have been insufficiently powered due to our relatively small sample size. Third, there was not enough power to detect significant predictors in a multivariate model. In addition, the duration of follow-up was relatively short. Finally, it was a single institutional study and selection bias may have been introduced. In conclusion, patients with post-LVAD RV failure requiring prolonged milrinone therapy have similar survival and postoperative complications as non-RV failure LVAD patients. There also appears to be a trend toward a decreased readmission rate in patients receiving milrinone. Patients receiving RVADs after LVAD implantation continue to have substantially reduced survival, despite our large clinical experience with managing RV failure. In patients who develop RV failure, age, preoperative renal failure, and previous cardiac surgery are potential predictors of milrinone infusion. Larger studies are needed to ascertain these findings, as predicting and reducing RV failure remains a significant challenge in LVAD therapy, as it yields significant morbidity and increases cost. References 1. Slaughter MS, Pagani FD, Rogers JG, et al; HeartMate II Clinical Investigators: Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant 29(4 Suppl): S1–39, 2010. 2. Slaughter MS, Rogers JG, Milano CA, et al; HeartMate II Investigators: Advanced heart failure treated with continuousflow left ventricular assist device. N Engl J Med 361: 2241– 2251, 2009. 3. Pagani FD, Miller LW, Russell SD, et al; HeartMate II Investigators: Extended mechanical circulatory support with a continuousflow rotary left ventricular assist device. J Am Coll Cardiol 54: 312–321, 2009. 4. John R, Kamdar F, Liao K, Colvin-Adams M, Boyle A, Joyce L: Improved survival and decreasing incidence of adverse events with the HeartMate II left ventricular assist device as bridge-totransplant therapy. Ann Thorac Surg 86: 1227–1235, 2008.
138 TSIOURIS et al. 5. Miller LW, Pagani FD, Russell SD, et al; HeartMate II Clinical Investigators: Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 357: 885–896, 2007. 6. Saito S, Sakaguchi T, Miyagawa S, et al: Recovery of right heart function with temporary right ventricular assist using a centrifugal pump in patients with severe biventricular failure. J Heart Lung Transplant 31: 858–864, 2012. 7. 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 73: 745–750, 2002. 8. Furukawa K, Motomura T, Nosé Y: Right ventricular failure after left ventricular assist device implantation: The need for an implantable right ventricular assist device. Artif Organs 29: 369–377, 2005. 9. Dang NC, Topkara VK, Mercando M, et al: Right heart failure after left ventricular assist device implantation in patients with chronic congestive heart failure. J Heart Lung Transplant 25: 1–6, 2006. 10. Kormos RL, Teuteberg JJ, Pagani FD, et al; HeartMate II Clinical Investigators: Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: Incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg 139: 1316–1324, 2010. 11. Takeda K, Naka Y, Yang JA, et al: Outcome of unplanned right ventricular assist device support for severe right heart failure after implantable left ventricular assist device insertion. J Heart Lung Transplant 33: 141–148, 2014. 12. Kormos RL: The right heart failure dilemma in the era of left ventricular assist devices. J Heart Lung Transplant 33: 134–135, 2014. 13. Farrar DJ, Compton PG, Hershon JJ, Fonger JD, Hill JD: Right heart interaction with the mechanically assisted left heart. World J Surg 9: 89–102, 1985. 14. Farrar DJ: Ventricular interactions during mechanical circulatory support. Semin Thorac Cardiovasc Surg 6: 163–168, 1994.
15. Moon MR, Bolger AF, DeAnda A, et al: Septal function during left ventricular unloading. Circulation 95: 1320–1327, 1997. 16. MacGowan GA, Schueler S: Right heart failure after left ventricular assist device implantation: Early and late. Curr Opin Cardiol 27: 296–300, 2012. 17. 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 106(12 Suppl 1): I198–I202, 2002. 18. Matthews JC, Koelling TM, Pagani FD, Aaronson KD: The right ventricular failure risk score a pre-operative tool for assessing the risk of right ventricular failure in left ventricular assist device candidates. J Am Coll Cardiol 51: 2163–2172, 2008. 19. Borgi J, Tsiouris A, Hodari A, Cogan CM, Paone G, Morgan JA: Significance of postoperative acute renal failure after continuous-flow left ventricular assist device implantation. Ann Thorac Surg 95: 163–169, 2013. 20. Toma M, Starling RC: Inotropic therapy for end-stage heart failure patients. Curr Treat Options Cardiovasc Med 12: 409–419, 2010. 21. Ahmad T, Patel CB, Milano CA, Rogers JG: When the heart runs out of heartbeats: Treatment options for refractory end-stage heart failure. Circulation 125: 2948–2955, 2012. 22. Hauptman PJ, Mikolajczak P, George A, et al: Chronic inotropic therapy in end-stage heart failure. Am Heart J 152: 1096.e1– 1096.e8, 2006. 23. Upadya S, Lee FA, Saldarriaga C, et al: Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure. J Heart Lung Transplant 23: 466–472, 2004. 24. Morgan JA, John R, Lee BJ, Oz MC, Naka Y: Is severe right ventricular failure in left ventricular assist device recipients a risk factor for unsuccessful bridging to transplant and post-transplant mortality. Ann Thorac Surg 77: 859–863, 2004.
