Relation of Left Ventricular Assist Device Infections With Cardiac Transplant Outcomes

Abstract

Left ventricular assist device (LVAD)–specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT. Left ventricular assist device (LVAD)–specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT. Left ventricular assist devices (LVADs) are frequently implanted as a bridge to transplantation for patients with end-stage heart failure awaiting heart transplant (HT).1Stehlik J Edwards LB Kucheryavaya AY Aurora P Christie JD Kirk R Dobbels F Rahmel AO Hertz MI The registry of the international society for heart and lung transplantation: twenty-seventh official adult heart transplant report–2010.J Heart Lung Transplant. 2010; 29: 1089-1103Abstract Full Text Full Text PDF PubMed Scopus (389) Google Scholar,2Ehsan A Zeymo A McDermott J Shara NM Sellke FW Yousefzai R Al-Refaie WB Utilization of left ventricular assist devices in vulnerable adults across Medicaid expansion [published correction appears in J Surg Res 2020;256:704].J Surg Res. 2019; 243: 503-508Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar From 2010 to 2018, approximately 43% of the nearly 37,000 worldwide HT recipients had a durable LVAD in place at the time of transplantation.3The International Society for Heart and Lung Transplantation. International Thoracic Organ Transplant (TTX) registry data slides: adult heart transplantation statistics, 2019. Available at: https://ishltregistries.org/registries/slides.asp. Accessed on November 4, 2019.Google Scholar Although LVAD therapy has afforded improved quality of life and survival for patients on the waiting list, they are still limited by adverse events, the most common of which are LVAD-specific infections (LSIs). Data on the impact of LSI on post-HT outcomes come from reports limited by small numbers of patients with older-generation LVADs and show conflicting findings. Although LSIs are considered cured with the removal of hardware at the time of HT, the ensuing inflammatory response in the perioperative setting may adversely affect short-term outcomes. We hypothesized that LSIs would be associated with higher incidence of acute renal failure (ARF), allograft rejection, and mortality at 30 days after HT and allograft rejection and death at 1 year in HT patients bridged with contemporary LVAD therapy. A retrospective analysis at our institution was conducted for patients who underwent HT from February 2012 to August 2019 bridged with a durable LVAD. Durable LVADs included the HeartMate II and HeartMate 3 LVAD (Abbott Laboratories, Abbott Park, Illinois) and the HeartWare HVAD (Medtronic, Minneapolis, Minnesota). The study was approved by the institutional review board at Icahn School of Medicine at Mount Sinai (New York, New York). Patients were grouped by the presence or absence of an LSI while on LVAD support, further defined in accordance with the 2011 International Society for Heart and Lung Transplantation consensus statement, which states “infections that are specific to patients with ventricular assist devices, are related to the device hardware, and do not occur in non-ventricular assist device patients; (including) pump and cannula infections, pocket infections, and percutaneous driveline infections.”4Hannan MM Husain S Mattner F Danziger-Isakov L Drew RJ Corey GR Schueler S Holman WL Lawler LP Gordon SM Mahon NG Herre JM Gould K Montoya JG Padera RF Kormos RL Conte JV Mooney ML International Society for Heart and Lung TransplantationWorking formulation for the standardization of definitions of infections in patients using ventricular assist devices.J Heart Lung Transplant. 2011; 30: 375-384Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar The presence of LSI was determined by chart review by 3 physicians (AP, MH, JF) and the microbiology of cultured organisms. Antibiotic regimen and route if given for this indication were recorded. Patient characteristics including demographics, co-morbid conditions, and clinical data were collected at the time of HT. Intraoperative data were collected from anesthesia reports and corroborated with operative notes, including the severity of infection, ischemia time, cardiopulmonary bypass time, units of packed red blood cells received intraoperatively, and blood salvaged using Cell Saver (Haemonetics, Braintree, Massachusetts). Hemodynamic data, including cardiac output, cardiac index, and systemic vascular resistance, were collected postoperatively from documented Swan-Ganz pulmonary artery catheter measurements on arrival to the cardiothoracic intensive care unit (ICU), between 8 and 12 hours after arrival, and at 24 hours. In all patients, we performed orthotopic HT by way of reoperative sternotomy using standard approaches. The entire LVAD was dissected out and mobilized before cardiectomy and the driveline transected as it exited the mediastinum. The recipient heart and the LVAD pump were then removed en bloc. If protective expanded polytetrafluorethylene sheets (Gore-Tex; W.L. Gore, Flagstaff, Arizona) had been placed, these were removed in entirety. If there was evidence of mediastinal infection, the pericardial well was washed out copiously with saline solution, and any potentially infected tissue was debrided before implantation of the allograft. The heart was then implanted. After weaning off bypass and securing of hemostasis, the LVAD driveline was explanted. The abdominal wall was debrided where necessary. For patients with infection, a drain was placed in the driveline tract. The driveline exit site was excised and debrided and was then either closed primarily or left to heal by secondary intention, depending on severity of infection. We removed all LVAD material at the time of transplantation. The short-term primary outcome was a composite of ARF, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within the first year after HT. Allograft rejection was defined as antibody-mediated rejection (pathologic antibody-mediated rejection ≥1), acute cellular rejection ≥2R as seen on endomyocardial biopsy specimen, or hemodynamic compromise with graft failure.5Stewart S Winters GL Fishbein MC Tazelaar HD Kobashigawa J Abrams J Andersen CB Angelini A Berry GJ Burke MM Demetris AJ Hammond E Itescu S Marboe CC McManus B Reed EF Reinsmoen NL Rodriguez ER Rose AG Rose M Suciu-Focia N Zeevi A Billingham ME Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.J Heart Lung Transplant. 2005; 24: 1710-1720Abstract Full Text Full Text PDF PubMed Scopus (1277) Google Scholar,6Colvin MM Cook JL Chang P Francis G Hsu DT Kiernan MS Kobashigawa JA Lindenfeld JA Masri SC Miller D O'Connell J Rodriguez ER Rosengard B Self S White-Williams C Zeevi A American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical CardiologyAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Cardiopulmonary Critical Care, Perioperative and ResuscitationAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Disease in the YoungAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke NursingAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Radiology and InterventionAmerican Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Surgery and AnesthesiaAntibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association.Circulation. 2015; 131: 1608-1639Crossref PubMed Scopus (162) Google Scholar ARF was classified as (1) a threefold increase in creatinine from patient's baseline, (2) an increase in creatinine to ≥5.0 mg/100 ml for ≥48 hours after HT, or (3) new requirement for initiation of renal replacement therapy (continuous venovenous hemofiltration or hemodialysis) during index hospitalization.7Mehta RL Kellum JA Shah SV Molitoris BA Ronco C Warnock DG Levin A Acute Kidney Injury NetworkAcute kidney injury network: report of an initiative to improve outcomes in acute kidney injury.Crit Care. 2007; 11: R31Crossref PubMed Scopus (4995) Google Scholar Transplant rejection and mortality were assessed until 1 year after HT. To explore potential mechanisms by which LSIs may have been associated with worse post-HT outcomes, the presence of perioperative vasoplegia was assessed. Vasoplegia was considered present if the following criteria were met: (1) vasopressor or inotropic support (epinephrine/norepinephrine ≥150 ng/kg/min, dopamine ≥10 μg/kg/min, or vasopressin ≥4 U/hour) at any time point within the first 24 hours of HT along with (2) systemic vascular resistance <800 dyne × s/cm5 without hemodynamic right-sided heart failure or (3) any use of methylene blue or vitamin B12 complex within 24 hours of HT. Right-sided heart failure was considered if central venous pressure >15 mm Hg and cardiac index <2.2 L/min/m2 or inotropic support >14 days.8Levin MA Lin HM Castillo JG Adams DH Reich DL Fischer GW Early on-cardiopulmonary bypass hypotension and other factors associated with vasoplegic syndrome.Circulation. 2009; 120: 1664-1671Crossref PubMed Scopus (145) Google Scholar This definition used here is consistently used at our institution and is based on measurements to the We the outcomes based on this definition with vasoplegia determined by the which has in of hemodynamic cardiopulmonary after cardiac and not The is dopamine vasopressin there is no consensus on a definition of the of our institutional all patients received standard of a an and or was not regimen was as by the heart failure In was or based on the severity of the infection. regimen and of was determined based on from the clinical and outcomes were between the 2 using and for and and for and for and of Organ were to the of LSI with the primary The of time to the short-term and long-term outcomes was using the and between the were assessed using a were to the of LSI with time to the short-term and long-term outcomes. were conducted using The was at = A of 111 patients underwent HT from LVAD support between February 2012 and August 2019 at our institution patients = had LVADs implanted with a bridge to transplantation However, patients were implanted with bridge to or therapy indication before being for transplant patients were for at 1 year after HT. Of the 63 patients had a of LSI. Patients with LSI were more to have a higher vs p = have a of use vs p = and have the vs p with patients without LSI. there were no in index, device on LVAD support, or therapy and clinical characteristics of LVAD-specific and no LVAD-specific patients = = LVAD-specific = do not were used for and for of had LVAD placed using a = = = = = = = = HeartMate = HeartMate HVAD = heart ventricular assist = = LVAD = left ventricular assist = standard = for Organ on LVAD in of or of of p do not were used for and for had LVAD placed using a = = = = = = = = HeartMate = HeartMate HVAD = heart ventricular assist = = LVAD = left ventricular assist = standard = for Organ in a new the 63 patients with LSI during LVAD support before HT, had driveline infections, 2 had infections, and 1 had a infection. There was an of = and = with = with and = where no was all patients with LSI = were on with = on and = on at the time of HT. In patients with LSI with those without no difference was in vs p = cardiopulmonary bypass time vs p = packed red blood cells vs 3 p = or by way of the Cell Saver device vs p = and transplant characteristics of LVAD-specific and no LVAD-specific patients = = LVAD-specific = were used for all p = cardiopulmonary = LVAD = left ventricular assist = packed red blood time in time in in in were used for all p = cardiopulmonary = LVAD = left ventricular assist = packed red blood in a new Of the 111 HT patients bridged with LVAD support, = the 30-day outcome of a composite of ARF, allograft rejection, or death after = the 1-year composite outcome of allograft rejection and death There was no difference in the 30-day or 1-year composite end point between patients with LSI and those without LSI (30% vs 25%, p = and vs 40%, p = A analysis of the 30-day and 1-year outcomes are in there was no difference in the of the composite outcomes or in the secondary outcomes, including of (7 vs p = and of vs p = In a LSI was not associated with the primary outcome to After for and LSI with the primary outcome to of LVAD-specific and no LVAD-specific patients = = LVAD-specific = do not or were used for and for composite at 30 rejection at 30 ARF at 30 composite at 1 rejection at 1 of in of in on arrival, at at p do not or were used for and for in a new of LSI on long-term outcome of allograft rejection and death within 1 year after HT. = of short-term composite = in vs vs vs in a new The incidence of vasoplegia in the was = with = in the LSI group and = in the group without LSI = 0.3). In there was no difference in the on arrival vs p = at 8 hours vs p = and at 24 hours vs p = after in the approximately of all patients awaiting heart transplantation bridged with LVAD support in the a of patients are vulnerable to adverse before HT, N M CB J A SC R R A BA G F K AJ A D D A J P 3 left ventricular assist device J 2019; PubMed Scopus Google Scholar data to the impact of LSI on post-HT outcomes. In this single-center retrospective study of more HT recipients bridged with LVAD support, more had LSI. However, presence was associated with the short-term composite outcome of ARF, allograft rejection, or mortality at 30 days after HT associated with the 1-year composite end point of allograft rejection and death after HT. LSI was not associated with or of at the time of HT. LVAD therapy has to be a for patients with end-stage heart failure awaiting HT. in LVAD device and the of this to be the most to long-term survival of N M CB J A SC R R A BA G F K AJ A D D A J P 3 left ventricular assist device J 2019; PubMed Scopus Google Scholar therapy with and and short-term they are transplantation the long-term for LSI in all of the infected hardware be The presence of LSI afforded a higher on the transplant waiting but the to the heart in the not patients on LVAD support to a but to patients with associated with the The of LSI be associated with adverse after HT is but be in of this that have this have NG L N of heart transplant after left ventricular assist device specific and related 2015; Full Text Full Text PDF PubMed Scopus Google Gordon RJ MC of left ventricular assist device on Heart Lung Transplant. 2009; Full Text Full Text PDF PubMed Scopus Google J of ventricular assist device on an analysis of the of Full Text Full Text PDF PubMed Scopus Google MA Heart transplantation outcomes in patients with left ventricular assist Heart Lung Transplant. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar 3 no with outcomes but had a of patients with from to with the seen in our NG L N of heart transplant after left ventricular assist device specific and related 2015; Full Text Full Text PDF PubMed Scopus Google Gordon RJ MC of left ventricular assist device on Heart Lung Transplant. 2009; Full Text Full Text PDF PubMed Scopus Google J of ventricular assist device on an analysis of the of Full Text Full Text PDF PubMed Scopus Google Scholar In the first of these, the on patients with LSI who underwent HT, and their post-HT outcomes were to patients without NG L N of heart transplant after left ventricular assist device specific and related 2015; Full Text Full Text PDF PubMed Scopus Google Scholar in no difference in survival in patients with and without there were data on or of Gordon RJ MC of left ventricular assist device on Heart Lung Transplant. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar registry the impact of all on post-HT outcomes have The of these by included patients and a of death at 1 year after an LVAD bridge to HT in patients with device with patients using a 30-day time for indication without D S R D M M of assist on graft Full Text Full Text PDF PubMed Scopus Google Scholar registry analysis performed by MA Heart transplantation outcomes in patients with left ventricular assist Heart Lung Transplant. 2015; Full Text Full Text PDF PubMed Scopus Google Scholar survival in patients with The most analysis by included patients on LVAD support between and and that of rejection may be with support, there was no difference in post-HT survival based on LVAD J of ventricular assist device on an analysis of the of Full Text Full Text PDF PubMed Scopus Google Scholar a review the and that LSI not affect mortality after D AJ M The impact of left ventricular assist device infections on transplant a review and 2019; PubMed Scopus Google Scholar a of definition for LSI across and the absence of data and the of infection, these data be with To our our study of the single-center contemporary the impact of LSI on post-HT outcomes, including patients on the most used 3 LVAD. The definition of LSI was based on the criteria by the International of Heart and Lung Transplantation MM Husain S Mattner F Danziger-Isakov L Drew RJ Corey GR Schueler S Holman WL Lawler LP Gordon SM Mahon NG Herre JM Gould K Montoya JG Padera RF Kormos RL Conte JV Mooney ML International Society for Heart and Lung TransplantationWorking formulation for the standardization of definitions of infections in patients using ventricular assist devices.J Heart Lung Transplant. 2011; 30: 375-384Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar In our LSIs were in approximately of the The of LSIs were to driveline infections, and there was an of and organisms. Of the the impact of in patients with LVAD who underwent HT, NG L N of heart transplant after left ventricular assist device specific and related 2015; Full Text Full Text PDF PubMed Scopus Google Scholar microbiology and between and organisms. The composite end point of ARF, rejection, and mortality at 30 days after HT was based on the that the presence of infection, in with would more a inflammatory response in the perioperative in R S F J R M A C R M L Early of and in left ventricular assist device recipients with failure 2010; PubMed Google N N M A of in patients cardiopulmonary Full Text PDF PubMed Google Scholar Vasoplegia to a worse and has been associated with of and The of vasoplegia to adverse outcomes as failure, and of the MA Lin HM Castillo JG Adams DH Reich DL Fischer GW Early on-cardiopulmonary bypass hypotension and other factors associated with vasoplegic syndrome.Circulation. 2009; 120: 1664-1671Crossref PubMed Scopus (145) Google E after heart Surg Google L P P J systemic vascular resistance after cardiopulmonary and clinical JG M S JD factors and outcomes for following cardiac J PubMed Scopus Google JG ML RJ as a of and mortality in after cardiopulmonary 2010; 11: PubMed Scopus Google Scholar In the use of to as renal failure, which in may to adverse outcomes. We that of patients had perioperative Although vasoplegia more frequently in patients with the difference was not This was further by the absence of difference in the which has been used to hemodynamic cardiopulmonary after cardiac JG ML RJ as a of and mortality in after cardiopulmonary 2010; 11: PubMed Scopus Google S after heart a of adverse Transplant. PubMed Scopus Google K as a of and mortality in adults after cardiac with cardiopulmonary PubMed Scopus Google J A J K M of following left ventricular assist device Heart Lung Transplant. 2019; Full Text Full Text PDF PubMed Scopus Google Scholar The presence of LSI not affect the of perioperative renal failure or or of and it not the of allograft rejection or mortality within 1 year of HT. In our LSI was more common in and was associated with higher but not with index as in sternotomy and the of LVAD support not affect the incidence of LSI. that LSIs do not to negatively affect outcomes. However, LSIs to significantly to for patients on LVAD LSIs result in care are the of and increase of for patients on MS R K M JG in for left ventricular assist device 2011; PubMed Scopus Google JM M Left ventricular assist device a PubMed Scopus Google Scholar clinical care and are to further the most to and This study has The first is that it is a single-center study that is to and In the small of patients in the may the to small the of the single-center patients may have been for device implantation and cardiac transplantation in a and this may have the In in this contemporary of patients on LVAD support, the presence of the short-term outcome of ARF, allograft rejection, or death at 30 days after HT post-HT rejection or survival at 1

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